Untitled - Asociacion Medica de Puerto Rico

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BOLETIN
Médico Científico de la Asociación Médica de Puerto Rico
Año 2013 - Volumen 105 - Número 1
Contenido
Catalogado en Cumulative Index e Index Medicus Listed in Cumulative Index and Index Medicus
No. ISSN-0004-4849. Registrado en Latindex -Sistema Regional de Información en Línea para
Revistas Científicas de América Latina, el Caribe, España y Portugal
Mensaje del Presidente
5
El issue de los medicamentos originales
patentizados, bio-equivalentes y genéricos
Natalio Izquierdo Encarnación, MD
Original Article/Artículos Originales
40
Laparoscopic management of an adnexal
torsion with transabdominal oophoropexy
performed in a first trimester pregnant
woman: a case report
Omar Pérez-Rodriguez MD, Alexandra Ortiz-
Oramas MD, Brayan Stuart- Vazquez MD
9
Pregnancy after liver transplantation
Ronald López-Cepero MD, Alberto de la Vega MD, Lauren Lynch MD
42
Chylous jejunal cyst causing volvulus in a child: Case report and literature review
Liliana Guzmán MD, Eittel Oppenheimer MD, Humberto Lugo-Vicente MD, Maria Correa MD
14
Effectiveness and safety of lidocaine in
the induction of fetal cardiac asystole for second
trimester pregnancy termination
Ronald López-Cepero MD, Lauren Lynch MD, Alberto de la Vega MD
48
An unusual presentation of herpes simplex in an immunocompromised patient
Francisco Fernández González MD,
José Betancourt MD, Juan C. Malpica MD,
Iván Laboy MD, Miguel Colón MD
18
HLA Class I & II Alleles in multiple sclerosis
patients from Puerto Rico
María T. Miranda MD, Erick Suárez PhD, Muneer Abbas PhD, Ángel Chinea MD, Rafael Tosado PhD, Ida A Mejías PhD, Nawal Boukli PhD, Georgia M Dunston PhD
51
Thoracic endometriosis: first reported case in Puerto Rico and review of literature
Carlos García Gubern MD, Lissandra
Colon Rolón MD, Orlando Vazquez Torres MD, Gretchen Martinez Alayón MD, Alexis Santos Santiago MD, Eugenio Mulero Portela MD
24
EIWA-III Measures of cognitive function in young Puerto Rico patients with epileps
Karla Narváez Pérez PhD, Leila Fernández Crespo PhD, María Teresa Miranda MD,
Frances Boulón Diaz PhD
54
Agenesia congenita de huesos craneales asociada a hidrocefalia: Reporte de caso
Luis Rafael Moscote-Salazar, Sandra
Milena Castellar-Leones, Gabriel Alcalá-Cerra, Juan José Gutiérrez-Paternina
Case Reports / Reporte de Casos
Review Article/Artículo de Reseña
32
Prenatal diagnosis of a vein of Galen
aneurysmal malformation using color Doppler
Ultrasound: a case report
Ronald López-Cepero MD, Alberto de la Vega MD, Lauren Lynch MD
36
Chorioangioma: an uncommon cause of hydramnios and consequent preterm labor in second trimester of pregnancy
Gianni Rodríguez-Ayala MD, Alberto de
la Vega MD, María Correa-Rivas MD,
Alexandra Jímenez MD
57
Hashimoto’s encephalopathy: An
underdiagnosed clinical entity
José Hernán Martínez MD, Oberto Torres MD, Michelle M. Mangual MD, Coromoto Palermo MD, Carlos Figueroa MD, Mónica Santiago MD,
María de Lourdes Miranda MD, Eva González MD
Diseño Gráfico e Ilustración digital de cubierta realizados por
Juan Laborde-Crocela en la Oficina de Informática de la AMPR.
Impreso en los talleres gráficos digitales de la Asociación Médica de Puerto Rico
E-mail:[email protected]
ILUSTRACION DE PORTADA
Natalio Izquierdo, M.D.
La Medicina y la Farmacia ayudan a la Salud.
Medio acrílico sobre lienzo 48 X 60 pulgadas 2013
Editorial Article/Artículo Editorial
62
Epidemiology of coronary heart disease:
The Puerto Rico heart health program
revisted
Mario R. García-Palmieri MD
OFICINAS ADMINISTRATIVAS
SUBSCRIPCIONES Y ANUNCIOS
Asociación Médica de Puerto Rico
PO Box 9387 • SANTURCE, Puerto Rico 00908-9387
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ANUNCIOS EN BOLETIN, WEBSITE
y NEWSLETTER
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Web Site: www.asocmedpr.org
4
JUNTA DE DIRECTORES
Dr. Natalio Izquierdo Encarnación
Dra. Wanda G. Vélez Andújar
Dr. Raúl G. Castellanos Bran
Dr. Pedro J. Zayas Santos
Dra. Ilsa Figueroa Dra. Hilda Ocasio Maldonado
Dr. Raúl A. Yordán Rivera
Dr. Jaime M. Díaz Hernández
Dr. Arturo Arché Matta
Dr. Juan Rodríguez Del Valle
Dr. Gonzalo González Liboy
Dr. Rolance G. Chavier Roper
Dr. Ricardo Marrero Santiago
Dr. Rafael Fernández Feliberti
Dra. Mildred R. Arché
Dr. Salvador Torrós Romeu
Dra. Daisy Quirós
Presidente
Pres. Electo
Presidente Saliente
Tesorero
Secretaria
Vicepresidenta AMPR
Vicepresidente AMPR
Vicepresidente AMPR
Pres. Cámara Delegados
Vicepres. Cámara Delegados
Delegado AMA
Delegado AMA
Delegado Alt. AMA
Delegado Alterno AMA
Pres. Distrito Central
Pres. Distrito Este
Pres. Distrito Sur
JUNTA DE EDITORES
Objetivos
Humberto Lugo Vicente, MD, Presidente
Luis Izquierdo Mora, MD
Melvin Bonilla Félix, MD
Carlos González Oppenheimer, MD
Eduardo Santiago Delpin, MD
Francisco Joglar Pesquera, MD
Yocasta Brugal, MD
Juan Aranda Ramírez, MD
Francisco J. Muñiz Vázquez, MD
Walter Frontera, MD
Mario. R. García Palmieri, MD
Natalio Izquierdo Encarnación, MD
José Ginel Rodríguez, MD
La Asociación Médica de Puerto Rico es fundada
en el año de 1902, cuando por aquel entonces, el
insigne doctor Manuel Quevedo Báez ve la necesidad de aglutinar a la profesión médica puertorriqueña en un núcleo para la defensa de la colectividad
y así fomentar el contínuo progreso de la ciencia y
el arte de la medicina y el mejoramiento de la salud
del pueblo de Puerto Rico. Tras vencer incontables
dificultades e inconvenientes naturales de la época,
se celebró la asamblea constituyente el día 21 de
septiembre de 1902, en el salón de sesiones de la
Cámara de Delegados en la ciudad de San Juan.
Reserva de derechos
El “Boletín” se distribuye a los médicos y estudiantes de medicina de Puerto Rico y se publica en versión digital en
www.asocmedpr.org.
Todo anuncio que se publique en el Boletín de la Asociación Médica de Puerto Rico deberá cumplir con las normas
establecidas por la Asociación Médica de Puerto Rico y la Asociación Médica Americana.
La Asociación Médica de Puerto Rico no se hace responsable por los productos o servicios anunciados.
La publicación de los mismos no necesariamente implica el endoso de la Asociación Médica de Puerto Rico.
Todo anuncio para ser publicado debe reunir las normas establecidas por la publicación. Todo material debe entregarse listo para la imprenta y con sesenta días de anterioridad a su publicación.
La AMPR no se hará responsable por material y/o artículos que no cumplan con estos requisitos.
Todo artículo recibido y/o publicado está sujeto a las normas y reglamentos de la Asociación Médica de Puerto Rico.
Ningún artículo que haya sido previamente publicado será aceptado para esta publicación. La Asociación Médica de
Puerto Rico no se hace responsable por las opiniones expresadas o puntos de vista vertidos por los autores, a menos
que esta opinión esté claramente expresada y/o definida den tro del contexto del artículo.
Todos los derechos reservados. El Boletín está totalmente protegido por la ley de derechos del autor y ninguna persona o entidad puede reproducir total o parcialmente el material que aparezca publicado sin el permiso escrito de los
autores.
Mensaje del
Presidente
Natalio Izquierdo
Encarnación, MD
5
El issue de los medicamentos
originales patentizados,
bio-equivalentes y genéricos
U
na de las quejas principales de los pacientes hoy día es que van a la Farmacia y
el plan no le cubre la medicina. Regresan al
médico a buscar otra receta. A pesar de que
el paciente estaba controlado con un medicamento original, el paciente pide al médico que
le cambie la receta por razones económicas.
El médico la cambia inspirado en Francis Peabody, que “el secreto del cuidado del paciente
consiste en preocuparse por el paciente”.
¿Por qué el médico le preocupa esta queja
contemporánea? Primero hablemos del valor
del producto. Porque sabemos que el medicamento bio-equivalente no es igual al original.
Por ley federal, el bio-equivalente puede ser
hasta 20% menos efectivo. ¿Le gustaría que
su dólar valiese 80 centavos? ¿Le gustaría
que le dieran 20% menos del producto que
usted compra en el colmado o de gasolina?
Pues eso es lo que puede pasar cuando sirven
un medicamento bio-equivalente. El problema
es que le puede quitar sólo el 80% del dolor.
En términos de los pacientes del glaucoma, el
descontrol de la presión intraocular conduce a
la ceguera. En términos del paciente cardiaco,
el descontrol de la angina y la isquemia, puede
significar la muerte.
Por otro lado, los bio-equivalentes, son equivalentes al original, pero no necesariamente
son equivalentes entre ellos. Por ejemplo: el
análogo de prostaglandinas de nombre comercial Xalatan, que se usa para tratar el glaucoma, tiene alrededor de ocho productos bioequivalentes en el mercado, para sustituir el
original. No todas los bio-equivalentes trabajan igual, ni penetran el ojo igual, ni tienen el
mismo preservante. Tampoco los preservantes
ni vehículos del medicamento son iguales y
esto hace que el paciente no tolere las gotas
de la misma forma.
Algunos desarrollan hipersensibilidad al producto para siempre. Desafortunadamente
cada vez que el paciente vuelve a la farmacia,
le sirven un bio-equivalente que es producido
por una compañía distinta, por ende, pude ser
distinto al original y distinto al vio-equivalente
que le entregaron el mes anterior.
La ley en Puerto Rico dice que la etiqueta de
los medicamentos debe incluir el nombre del
manufacturero del producto bio-equivalente.
Es menester mencionar que esto no está
pasando en PR siempre. Entonces el manufacturero puede variar de mes en mes y por
ende la presentación. Hay que mejorar en el
cumplimiento de esta ley. Es preocupante pensar, que si la bio-equivalencia entre los diferentes medicamentos bio-equivalentes no es
requerida por el FDA, entonces no conviene
al paciente que se le cambie de un bio-equivalente al otro. Los pacientes van a estar controlados con uno sí y con otros no.
Desafortunadamente, no todas las botellas
son iguales, ni las tapas de las botellas, ni los
goteros. Esta es otra preocupación. Las gotas
oftálmicas originales tienen tapas de colores,
que codifican para la clase del producto. Por
ejemplo: por décadas se ha usado el tapón
verde para las gotas de pilocarpina, el tapón
amarillo para las gotas de beta-bloqueadores
y recientemente el tapón azul turquesa para
las gotas de análogos de prostaglandinas. Sin
embargo los fabricantes de los bio-equivalentes y genéricos, no tienen que igualar el color
del tapón de la gota original, o que la botella
se asemeje el empaque original. Esto tiene un
peligro: que el paciente puede estar usando la
misma gota dos veces. Si se toma doble dosis
de la pastilla para la presión sistémica, la vida
del paciente puede estar en peligro.
Por otro lado, el gotero de las botellas de
colirio original está calibrado. Esto es importante porque el fornix del ojo puede contener
un volumen pequeñísimo de las gotas oftálmicas que se instilen. Los goteros de los medicamentos oftálmicos originales están calibrados para que el paciente pueda aprovechar
el máximo del volumen en la botella del producto, que sabemos es de tres a cinco centímetros cúbicos (una cucharadita o menos).
Se desconoce la calibración de los goteros de
los colirios bio-equivalentes. Todo lo que sea
en exceso a la gota calibrada es un desperdicio, porque se sale del ojo. El paciente pierde
dinero en una gota que sale a veces de un
volumen, a veces de otro de un gotero que no
está calibrado.
Sirva todo esto para hacer un llamado a los
que escogen los medicamentos que van al formulario de los planes médicos.
Sirva todo esto para que se pida a las autoridades que administran para que se le dé la
oportunidad al paciente a escoger. Recomiendo que se le aplique el gasto por el costo del
medicamento bio-equivalente, al costo del medicamento original en la farmacia.
6
Asociación Médica
de Puerto Rico
Objetivos
La Asociación Médica de Puerto Rico es fundada en el año de
1902, cuando por aquel entonces, el insigne doctor Manuel
Quevedo Báez ve la necesidad de aglutinar a la profesión médica puertorriqueña en un núcleo para la defensa de la colectividad y así fomentar el contínuo progreso de la ciencia y el arte de
la medicina y el mejoramiento de la salud del pueblo de Puerto
Rico. Tras vencer incontables dificultades e inconvenientes naturales de la época, se celebró la asamblea constituyente el día
21 de septiembre de 1902, en el salón de sesiones de la Cámara de Delegados en la ciudad de San Juan.
Inscripción abierta para médicos de
Puerto Rico, USA e Islas del Caribe
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Por favor responda las siguientes preguntas:
Ha sido convicto por alguna felonía en los últimos 5 años?
Ha sido su licencia para practicar la medicina limitada, suspendida o revocada, en cualquier jurisdicción, en los últimos 5 años?
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FIRMA DEL SOLICITANTE
Original Article/Artículos Originales
Pregnancy after
liver
transplantation
9
Ronald López-Cepero MDa*, Alberto de la Vega
MDa, Lauren Lynch MDa
Department of Obstetrics and Gynecology, University of
Puerto Rico, School of Medicine, San Juan, Puerto Rico.
*Corresponding author: Ronald López-Cepero MD - University of Puerto Rico, Medical Sciences Campus, School
of Medicine, Department of Obstetrics and Gynecology,
PO BOX 365067 San Juan Puerto Rico 00936-5067. Email: [email protected]
a
ABSTRACT
Several reports on liver transplantation and pregnancy have been published recently.
Uncertainty remains regarding appropriate management of these patients. Methods: The
study included pregnant women of all ages with liver transplant referred to our center. A
total of eight patients were identified and qualified for our study. The following variables
were obtained: age, date of liver transplantation, date of conception, reasons for liver
transplantation, type of immunosuppressive therapy, complications during pregnancy,
gestational age at birth, birth weight, mode of delivery, the interval of time from liver transplantation to conception and co-morbidity. Results: The mean age of our population was
24 years. Four of the eight were nulliparous. The mean time interval from transplantation
to pregnancy was eight years. The indication for liver transplantation in 75% of patients
was autoimmune hepatitis. Two cases were associated with viral hepatitis. Combination
therapy with more than one immunosuppressant was given to 75% of patients. The most
prevalent complication was pyelonephritis in (38%), followed by gestational thrombocytopenia and preeclampsia. Most deliveries (75%) were vaginal and at term (88%). The median
for gestational age was 39 weeks. The median birth weight was 2,898 grams. Conclusions:
This study proves that successful and uneventful pregnancies are likely in liver transplant
patients under optimal obstetric management.
Keywords: liver transplant, pregnancy, immunosuppressive therapy
INTRODUCTION
Infertility is common among women with
chronic liver disease. This is attributed mainly
to hormonal abnormalities affecting the hypothalamic-pituitary axis. In the majority of nonmenopausal women, resumption of normal
physiologic menstrual function and ability to
conceive is re-established after liver transplantation (1-2). Cundy and coworkers reported
that 82% of reproductive age women would
restore their normal menstrual cycle after
transplantation (3). In 1978, Walcott and colleagues reported the first case of a successful
pregnancy in a liver transplant patient. At that
moment their concerns were primarily related
to the risks of organ transplant rejection and
the possibility of teratogenicity secondary to
immunosuppressive drugs. Both, the patient
and infant ended up with an outstanding outcome (4).
Several case series reports on liver transplantation and pregnancy have been published in recent years. Uncertainty still remains regarding
appropriate obstetrical management of these
patients. It is likely that longer time interval between conception and liver transplant surgery
results in better pregnancy-related outcomes
(5-6). Framarino dei Malatesta et al, reported
that the group of pregnancies complicated by
hypertensive disorders was characterized by
a shorter timing between organ transplant and
conception, compared to uncomplicated cases (20 ± 15 vs. 59 ± 20 months, respectively,
p<0.01) (7). Studies also suggests that prolonging such period will require lower doses
of immunosuppressive drugs, all of which may
have some adverse effect on organogenesis
(8). Recommendations regarding management of acute rejection of the graft, or mode of
delivery, require individualization.
Management by maternal fetal medicine and
transplant organ specialists is of paramount
importance. Hypertensive disorders, infections
and prematurity are major adverse outcomes
that complicate these pregnancies (9). Furthermore, the economic burden posed by these
patients has not been clearly established.
In the early 1990s the National Transplantation
Pregnancy Registry (NTPR) was established.
It is a questionnaire-based data bank that is
completed by transplants recipients in North
America who voluntarily agree to provide information regarding their health status. Much information has been provided from this system
that permits analysis of information regarding
pregnancy and liver orthotic transplant patients. In this report, we review our experience
at the University District Hospital with pregnancies after liver transplantation, and provide
recommendations based on our findings.
METHODS
This is a descriptive retrospective study. The
study population included pregnant women
of all ages with liver transplant referred to our
center. A total of eight patients were identified
and qualified for our study. Information was obtained from the University Hospital Antenatal
Evaluation Unit data bank. All information was
anonymous and, thus, not subject to review
under FDA and OHRP guidelines. The following variables were obtained from each patient:
age, date of liver transplantation, date of conception, reasons for liver transplantation, type
of immunosuppressive therapy, complications
during pregnancy, if any, gestational age at
birth, birth weight, mode of delivery, the interval of time from liver transplantation to conception and co-morbidity.
Statistical analysis was performed using
SPSS (PASW 18) software program. Descriptive analysis was performed to describe frequencies, proportions, minimum, maximum,
means and medians ± standard deviations.
To determine the significance of the difference
between two proportions, two sided p values
were obtained from the Fisher’s exact test, using a 2x2 contingency table. This statistical test
was chosen because all cells had small counts
of less than 5.
No abortions or elective termination procedures were reviewed. Table 1 summarizes maternal and birth outcomes.
A. Maternal characteristics
The mean age of our population was 24 years
± 6.2. Only one patient was over 35 years old.
Four of the eight (50%) were nulliparous. The
mean time interval from transplantation to pregnancy was eight years ± 2.1 (4-10 yrs.). The indication for liver transplantation in 6/8 patients
(75%) was autoimmune hepatitis. Only two
cases were associated with viral hepatitis.
All our patients were treated with tacrolimus
for immunosuppression treatment. Two-thirds
were using prednisone. Combination therapy
with more than one immunosuppressant was
given to 6/8 (75%) of patients. Figure 1 describes the distribution of individuals and combined therapies used among them. Within our
study group, only three patients required additional medical treatment to prevent transplant
rejection; one of these included mycophenolate mofetil.
Figure 2 describes medical complications
with new onset during pregnancy. The most
prevalent complication was pyelonephritis in
3/8 (38%) of patients followed by gestational
thrombocytopenia (2/8) and pre-eclampsia
(2/8). Two of eight patients had diabetes, one
pre-gestational and one gestational. One patient developed HELLP syndrome and pregnancy was terminated at 32 weeks by cesarean section.
B. Birth characteristics
Most deliveries (6/8 or 75%) were vaginal and
at term (7/8 or 88%). The median for gestational age was 39 weeks ± 3. The median birth
weight was 2,898 grams ± 528. The lowest
percentile for birth weight was 15th in a preterm delivery. There were no stillborn or neonatal deaths.
All p values from our descriptive analysis were
not statistically significant. For that reason, no
statistical association between variables was
identified.
RESULTS
DISCUSSION
A total of eight pregnancies among eight patients were identified. Our study group consisted
on pregnancies carried beyond 20 weeks only.
This retrospective review accounts for eight
cases of pregnancies after liver transplantation.
10
This is the only study describing pregnant
women with a solid organ transplant in Puerto
Rico. Only viable pregnancies were included
because our hospital is a referral medical
center. Patients who had earlier pregnancy
interventions, such as therapeutic or spontaneous abortions, were likely managed by their
primary gynecologist and not referred to us.
Thus, we have no information regarding the incidence of early pregnancy losses among our
liver transplant patients. Previous investigators
have reported that 86% of these pregnancies
ended in first trimester abortion if less than 12
months occurred after transplant. In addition, if
more than 24 months passed between surgery
and conception, 78% reached viability (10).
Reproductive age women comprise a large
number of liver transplant patients (11). In our
population, the mean age (24 y/o) correlates
with that of the general non-transplanted population in Puerto Rico as reported by our Department of Health live statistics (12).
An important finding in our study is the fact
that most patients delivered vaginally (75%).
This is in sharp contrast to the medical report
by Jabiry et al in which 71% of patients were
delivered by cesarean sections (13). The reasons for this difference cannot be explained
based on maternal age (24 in ours vs. 27.9 in
their series), mean gestational age at delivery
(39 wks. in ours vs. 37.6 wks. in their series)
nor the mean birth weight, since theirs did not
differ significantly (2898 g in ours vs. 2725g in
their series). The main difference in mode of
delivery was most likely secondary to the low
incidence of pregnancy complications that we
experienced, with only two cases of pre-eclampsia and one of gestational diabetes, along
with the low incidence of maternal comorbidity.
This may be due to a relatively long average
time interval between transplant and pregnancy (8 years in ours vs. 4.3 years in their series).
Kohno and colleagues hypothesize that inadequate trophoblastic invasion might be secondary to higher levels of cytokines present in the
body immediately after transplantation (14). It
is also possible that this difference might be related to the fact that all our patients were treated with tacrolimus throughout pregnancy. The
use of this medication is believed to reduce the
incidence of complications among liver transplant patients (10).
We acknowledge that one of the limitations of
this study is the small sample size; this might
explain the lack of statistical significance between variables analyzed.
We recognize the inherent pitfalls of any retrospective analysis and acknowledge the need
for further prospective research in this subject.
This study proves that successful and uneventful pregnancies are likely in liver transplant patients under optimal conditions. It is likely that
a long interval between transplantation and
conception, and the continued use of tacrolimus during pregnancy are the main factors
involved in a successful outcome. These associations are of paramount interest and studies
should continue in this field. Liver transplantation alone may not pose a significant risk factor
for the outcome of pregnancy in the absence
of other complications.
REFERENCES
1. Bonanno C, Dove L. Pregnancy after liver transplantation. Semin Perinatol 2007;31:348-353.
2. De Koning ND, Haagsma EB. Normalization of
menstrual pattern after liver transplantation: consequences for contraception. Digestion 1990;46:239241.
3. Cundy TF, O’Grady JG, Williams R. Recovery of
menstruation and pregnancy after liver transplantation. Gut 1990;31:337-338.
4. Walcott WO, Derick DE, Jolley JJ, et al. Successful pregnancy in a liver transplant patient. Am J Obstet Gynecol 1978;132:340-341.
5. Surti B, Tan J, Saab S. Pregnancy and liver transplantation. Liver Intern 2008; 9:1200-1206.
6. Armenti VT, Herrine SK, Radomski JS, et al.
Pregnancy after liver transplantation. Liver Transpl
2000;6:671-685.
7. Framarino dei Malatesta ML, Rossi M, Rocca
Bianca, et al. Pregnancy after liver transplantation:
Report of 8 new cases and review of the literature.
Transpl Immunol 2006;15:297-302.
8. Heneghan MA, Sylvestre PB. Cholestatic disease of liver transplantation. Semin Gastrointest
Dis 2001;12:133-147.
9. Armenti VT, Radomski SS, Moritz MJ, et al. Report from the National Transplantation Pregnancy
Registry (NTPR): outcomes of pregnancy after
transplantation. Clin Transpl 2004.
10. Nagy S, Bush MC, Berkowitz R, et al. Pregnancy outcome in liver transplant recipients. Obstet
Gynecol 2003;102:121-128.
11. Jain AB, Reyes J, Marcos A, et al. Pregnancy
after liver transplantation with tacrolimus immunosuppression: a single center’s experience update at
13 years. Transplantation 2003;76:827-832.
12. Informe anual de estadísticas vitales: 2007 y
2008 [Departamento de Salud Gobierno de Puerto
12
Rico Web site]. December 2011. Available at:
http://prhsj.rcm.upr.edu/index.php/prhsj/about/
submissions#onlineSubmissions. Accessed July 7,
2012.
13. Jabiry-Zieniewicz Z, Bobrowska B, Pietrzak B,
et al. Mode of delivery in women after liver transplantation. Transplant Proc 2007;39:2796-2799.
14. Kohno T, Mizukami H, Suzuki M, et al. Interleukin-10-mediated inhibition of angiogenesis and tumor growth in mice bearing VGEF-producing ovarian cancer. Cancer 2003;16:5091-5094.
Acknowledgements
We want to thank Annette Pascual-Marrero,
MPH for her contributions in the statistical
analysis of this data. This work required no
sources of funding. The authors have no conflict of interest to disclose.
RESUMEN
Varios estudios sobre embarazadas
trasplantadas del hígado han sido publicados en los pasados años. El manejo de
estas pacientes continúa siendo complejo
y su conocimiento limitado. Métodos: Ocho
pacientes fueron identificadas y evaluadas
en el estudio. La edad materna, fecha del
trasplante, fecha de la concepción, criterio
para el trasplante, medicamentos utilizados, complicaciones gestacionales, peso
del recién nacido, modos de nacimiento,
intervalo desde el trasplante hasta la concepción y las comorbilidades fueron tabuladas. Se hizo un análisis descriptivo de
todas la variables recopiladas. Resultados:
La edad promedio de nuestra población
fue 24 años. La mitad de las pacientes eran
nulíparas. El promedio del intervalo entre el trasplante y la concepción fue de 8
años. La indicación para el trasplante en 6
pacientes fue hepatitis autoinmune (75%),
el resto fue por hepatitis viral. Se requirió
más de un medicamento inmunosupresor
en 75% de las pacientes. La complicación
materna más común fue la pielonefritis en
38% de los pacientes, seguida por la trombocitopenia gestacional y la preeclampsia.
La mayoría de los nacimientos fueron vaginales (75%) y a término (88%). El promedio
de la edad gestacional fue 39 semanas.
El peso promedio de los neonatos fue de
2,898 gramos. Conclusiones: Este estudio
demuestra que pacientes con trasplante
hepático pueden lograr embarazos saludables y exitosos de haber un cuidado obstétrico óptimo.
13
La Asociación Médica
vuelve al Dorado,
a la búsqueda de la
excelencia en
Educación Médica,
en pautas de
investigación científica,
en desarrollo de líderes
para el futuro.
Acérquese y únase a
nuestro esfuerzo
por el bienestar de la
salud y del Pueblo de
Puerto Rico
14
Effectiveness and
safety of lidocaine in
the induction of fetal
cardiac asystole for
second trimester
pregnancy termination
Ronald López-Cepero MDa*, Lauren Lynch MDa,
Alberto de la Vega MDa
a
INTRODUCTION
Induced abortion is currently one of the most
common surgical procedures performed by
women of reproductive age (1). The safety
of this procedure has been thoroughly established in randomized controlled trials (2-3).
Nonetheless, analyzing medical literature on
this topic remains very challenging for physicians, given the diversity of results provided
(4). In the United States, most abortion practitioners will induce fetal demise before second
trimester abortion. This is mostly done in order
to avoid potential claims of legal misconduct
against government regulations, such as the
Partial-Birth Abortion Ban Act (5). However,
the medical rationale behind this practice remains inconclusive for reasons other than the
one just mentioned.
The presence of a major congenital anomaly
in the fetus is a frequent indication for second
trimester pregnancy termination (6). This is
mainly due to the timing of ultrasound diagnosis, which occurs between 18-20 weeks of
gestation in more than half of the cases (7). In
patients with maternal indications for abortion,
late entry into prenatal care often delays the
procedure until the second trimester. This may
be due to not realizing that they are pregnant,
often because the pregnancy is unplanned.
Moreover, 50% of pregnancies in Puerto Rico
are unplanned (8). Similar statistics have been
previously reported in the U.S. (9).
ABSTRACT
The presence of a major congenital anomaly
is a frequent indication for late termination
of pregnancy. The possibility of the fetus
being born alive is significant, thus, feticide
prior to the procedure is desirable. The purpose of this study was to assess the safety
and efficacy of lidocaine 1% as a feticidal
agent prior to second trimester termination
of pregnancy. Methods: We conducted a
chart review of all patients who underwent a
second trimester termination of pregnancy
at our institution between March 2009 and
June 2012. We collected data regarding the
indication for the termination procedure,
gestational age, site of lidocaine injection,
dosage of lidocaine, need for additional to
produce asystole, and maternal complications. Results: We identified 54 patients
who underwent second trimester termination following injection with lidocaine.
Forty-six cases (85%) were done for major
fetal anomalies and 8 cases (15%) were for
maternal indications. The mean gestational
age was 22 weeks (SD=2.3). The mean volume of lidocaine 1% injected was 10.1 mL
(range: 5-40 mL). Asystole was achieved in
1-2 minutes following intracardiac administration. Intracardiac injection was successful in 45/46 (98%) of cases. Intrathoracic
administration was successful in 5/6 (83%).
This approach was chosen when cardiac
puncture was not effective. Two fetuses receiving an initial intraabdominal or umbilical vein injection required additional doses
of intracardiac lidocaine to produce asystole. There were no maternal complications.
Conclusions: Intracardiac administration
of lidocaine is an effective method to induce cardiac asystole for second trimester
pregnancy termination. Extra-cardiac injection, however, is less effective.
Index words: lidocaine, induction, fetal,
cardiac asystole, pregnancy, termination
The Society of Family Planning recommends
the use of feticidal agents prior to medical or
surgical abortion near viable gestational ages,
essentially to avoid signs of live birth, reducing
the emotional burden that frequently accompanies this process (10).
Most studies regarding the use of feticidal
agents focus primarily on their efficacy in causing fetal demise; yet, there is scarce pharmacokinetic information available for these agents
when used in this context. At the current time,
potassium chloride (KCl) is used more often by
infertility and perinatology specialties, whereas
digoxin is preferred by abortion providers (11).
In addition, Senat and colleagues have shown
that lidocaine is an effective feticidal agent
when used in dosages that pose little risk of
maternal toxicity (6). The purpose of this study
was to assess the safety and efficacy of lidocaine 1% as a feticidal agent prior to second
trimester termination of pregnancy.
METHODS
This is a descriptive retrospective study. We
conducted a chart review of all patients who
underwent a second trimester termination of
pregnancy at our institution between March
2009 and June 2012. Information was obtained
from the University Hospital Antepartum Unit
data bank. All information was anonymous,
and thus, not subject to review under FDA and
OHRP guidelines. We collected data regarding
the indication for the termination of pregnancy,
gestational age at the time of the procedure,
site of lidocaine injection, amount of lidocaine
used, the need for additional injections to produce asystole and maternal complications.
RESULTS
A total of 54 patients underwent second trimester pregnancy termination following feticidal injection during the study period. Forty-six
of the cases were done for major fetal anomalies (85%) and 8 were for maternal indications (15%). The mean gestational age was
22 weeks (SD=2.3). The mean volume of lidocaine 1% injected was 10.1 mL (range: 5-40
mL). Asystole was achieved in 1-2 minutes following intracardiac administration. Intracardiac
injection was successful in 45/46 (98%) of cases. Intrathoracic administration was successful
in 5/6 (83%). Fetuses receiving a single initial
intraabdominal or intravascular (cord) injection
required an additional intracardiac dose of lidocaine to produce asystole. There were no
maternal complications.
Table 1 lists the indications for the termination
of pregnancy, gestational age at the time of the
procedure, site of lidocaine injection, amount
of lidocaine used and the need for additional
injections to produce asystole.
DISCUSSION
In the United States, induction of fetal cardiac
asystole is mainly achieved with the administration of either KCL or digoxin. The use of
other drugs to induce fetal demise in this setting has been scarcely considered. This is one
of the few studies that report the use of a readily available local anesthetic agent for the induction of fetal cardiac asystole during second
trimester termination of pregnancy. Our report
shows that fetal injection of lidocaine is effective in this scenario. Successful and prompt
cessation of fetal cardiac activity was achieved
with low doses of the drug, minimizing the risk
of maternal toxicity. It has been established that
pregnancy does not enhance the toxic effects
of this agent, and that doses used for feticide
are far lower than those required causing any
maternal effects. Morishima, Finster, and others (12) studied lidocaine toxicity in pregnant
and non-pregnant sheep receiving a continuous intravenous drug infusion. They reported
that seizures occurred at 5.9 mg/kg (SD=0.6)
in the pregnant sheep and 5.8 mg/kg (SD=1.8)
in the non-pregnant sheep, whereas cardiac
arrest occurred at 40.7 mg/kg (SD=2.6) and
36.7 mg/kg (SD=3.3) in the pregnant and nonpregnant animals, respectively.
During the past three decades, several studies
have established the efficacy of KCl as a feticidal agent (13-18). In addition, some reports
suggest that induction of fetal demise with KCl
before abortion significantly shortens the termination procedure. In their retrospective review,
Elimian et al (19) compared induction to expulsion interval time in subjects who were injected with KCl before the procedure, with those
induced without pre-treatment. They found
that the induction to abortion interval was significantly shorter in the cardiac puncture group
compared with the control group (570 minutes
compared with 890 minutes, P = .006).
In physiological terms, if KCl enters the maternal circulatory system by accident when fetal
puncture is attempted, a life-threatening event
might follow. Recently, Coke and co-workers
(20) described a case of maternal cardiac arrest induced after fetal intracardiac injection of
KCl, evidencing the potential risk of this procedure.
Correspondingly, outcomes with the use of digoxin have been reported. A randomized study
by Jackson et al (21) assessed the efficacy
of digoxin in second trimester termination of
pregnancy. Their results showed no difference
15
in decreased operative time or blood loss between women who received pre-operative intra-amniotic digoxin and those given placebo.
In contrast, the group injected with digoxin
reported higher vomiting side effects (16.1%)
than those managed with placebo (3.1%). In
our group, there were no maternal side effects
described throughout the procedure.
REFERENCES
1. Jones RK. Abortion in the United States: incidence and access to services. Perspect Sex Reprod Health 2008;40:6–16.
2. Bartlett LA, Berg CJ, Shulman HB, et al. Risk factors for
legal induced abortion-related mortality in the United States.
Obstet Gynecol 2004;103:729–737.
3. Elam-Evans LD, Strauss LT, Herndon J, Parker WY, Bowens SV, Zane S, et al. Abortion surveillance–United States,
2000. MMWR CDC Surveill Summ 2003;52(SS- 12):1–32.
4. Borgatta L, Kapp N; Society of Family Planning. Clinical
guidelines. Labor induction abortion in the second trimester.
To our knowledge, similar results with lidocaine
Contraception 2011;81:4-18.
have been previously reported only once, us5. Haddad L, Yanow S, Delli-Bovi L, Cosby K, Weitz TA.
Changes in abortion provider practices in response to
ing the umbilical vein as the puncture site for
the Partial-Birth Abortion Ban Act of 2003. Contraception
injection (6). Senat and his group demonstrat2009;79:379-384.
ed a success rate of 92% in achieving asystole
6. Senat MV, Fischer C, Bernard JP, et al. The use of lidocaine
for fetocide in late termination of pregnancy. Intern J Obstet
without any maternal side effects. Our data
Gynecol 2003;110:296-300.
shows that although intrathoracic injection was
7. Gagnon A, Wilson RD, Allen VM, et al. Evaluation of preeffective, the most effective injection site to
natally diagnosed structural congenital anomalies. J Obstet
Gynaecol Can 2009;9:875-881.
achieve rapid asystole was intracardiac. Given
8. De la Vega A, Verdiales M. How does Maternal age afthe potential technical difficulties involved in
fect pregnancy planning in Puerto Rico? P R Health Sci J
achieving a cardiac puncture (maternal body
2002;21:127-128.
habitus, fetal position, placental location), the
9. Henshaw SK. Unintended pregnancy in the United States.
Fam Plann Perspect 1998;30:24–29.
use of lidocaine as a feticidal agent is best
10. Diedrich J, Drey E; Society of Family Planning. Induction
performed by an operator skilled in ultrasoundof fetal demise before abortion. Contraception 2010;81:462guided invasive procedures.
473.
11. Molaei M, Jones HE, Weiselberg T, et al. Effectiveness and safety of digoxin to induce fetal
demise prior to second-trimester abortion. Contraception 2008;77:223-225.
RESUMEN
12. Morishima HO, Finster M, Arthur GR, Covino BG. Pregnancy does not alter lidocaine toxicUn diagnóstico antenatal de anomalías congénitas letales
ity. Am J Obstet Gynecol 1990;162:1320-1324.
13. Bhide A, Sairam S, Hollis B, Thilaganathan
es una de las indicaciones para terminación del embarazo
B. Comparison of feticide carried out by cordodurante el segundo trimestre. En vista de que el feto puede
centesis versus cardiac puncture. Ultrasound
nacer vivo, producirle asístole antes del procedimiento es
Obstet Gynecol 2002;20:230–232.
deseable. El propósito de este estudio fue evaluar la efica14. Eddleman KA, Stone JL, Lynch L, Berkowcia de lidocaína al 1% como agente feticida en las termiitz RL. Selective termination of anomalous fenaciones de embarazos avanzados. Métodos: Se obtuvo
tuses in multifetal pregnancies: two hundred
cases at a single center. Am J Obstet Gynecol
información del banco de data de la unidad de anteparto
2002;187:1168–1172.
del Hospital Universitario sobre las pacientes a las cuales
15. Hern WM. Selective termination for fetal
se les realizaron terminaciones de embarazo durante el
anomaly/genetic disorder in twin pregnancy at
segundo trimestre. La indicación para el procedimiento,
32+ menstrual weeks. Report of four cases. Feedad gestacional al momento de la terminación, lugar de
tal Diagn Ther 2004;19:292–295.
16. Lynch L, Berkowitz RL, Chitkara U, Alvainyección, cantidad inyectada, dosis adicionales necesarrez M. First-trimester transabdominal multifetal
ias y las complicaciones maternas fueron tabuladas. Repregnancy reduction: a report of 85 cases. Obsultados: A 54 pacientes se les realizaron terminaciones
stet Gynecol 1990;75:735–738.
de embarazo, luego de haberse utilizado lidocaína como
17. Pasquini L, Pontello V, Kumar S. Intracaragente feticida previo al procedimiento. Cuarenta y seis
diac injection of potassium chloride as method
de los procedimientos fueron realizados debido a malforfor feticide: experience from a single UK tertiary
centre. BJOG 2008;115:528–531.
maciones congénitas letales (85%) y 8 debido a razones
18. Silva LV, Cecatti JG, Pinto e Silva JL, Amaral
maternas (15%). El promedio de edad gestacional fue 22
E, Barini R. Feticide does not modify duration of
semanas ±2.3. La cantidad de lidocaína al 1% inyectado
labor induction in cases of medical termination
fue 10.1 mL (5-40 mL). Se obtuvo asístole fetal en un períoof pregnancy. Fetal Diagn Ther 2008;23:192–
do aproximado de 1 a 2 minutos luego de la inyección. La
197.
administración intracardiaca se logró en 45 de 46 (98%)
19. Elimian A, Verma U, Tejani N. Effect of causing fetal cardiac asystole on second-trimester
casos. La administración intratorácica debido a no lograr
abortion. Obstet Gynecol 1999;94:139-141.
una inyección intratorácica fue efectiva en 5 de 6 casos
20. Coke GA, Baschat AA, Mighty HE, Malinow
(83%). Las 2 pacientes que recibieron inicialmente lidocaíAM. Maternal cardiac arrest associated with atna intraabdominal o intravascular requirieron una dosis
tempted fetal injection of potassium chloride. Int
adicional intracardiaca para producir asístole en el feto.
J Obstet Anesth 2004;13:287–290.
21. Jackson RA, Teplin VL, Drey EA, Thomas
No se registraron complicaciones maternas. Conclusión:
LJ, Darney PD. Digoxin to facilitate late secLa administración intracardiaca de lidocaína es efectiva
ond trimester abortion: a randomized, masked,
en producir asístole en el feto durante terminaciones de
placebo-controlled trial. Obstet Gynecol
embarazo en el segundo trimestre.
2001;97:471–476.
16
Table 1: Termination of pregnancy for fetal abnormalities and maternal indications: gestational age, indication and doses of lidocaine used for procedure.
17
18
HLA Class I &
II Alleles in Multiple
Sclerosis patients
from Puerto Rico
María T. Miranda MDa,b*, Erick Suárez PhDc,
Muneer Abbas PhDd, Ángel Chinea MDe, Rafael
Tosado PhDa, Ida A Mejías PhDa, Nawal Boukli
PhDf, Georgia M Dunston PhDd
Inter American University of Puerto Rico, Metropolitan
Campus, San Juan, Puerto Rico.
b
San Juan Bautista School of Medicine, Caguas, Puerto
Rico.
c
University of Puerto Rico, Medical Sciences Campus,
San Juan, Puerto Rico.
d
National Human Genome Center, Howard University,
Washington, DC.
e
San Juan MS Center, San Juan, Puerto Rico.
f
Biomedical Proteomics Facility, School of Medicine, Universidad Central del Caribe, Bayamón, Puerto Rico.
*Corresponding Author: María T. Miranda, MD - School of
Medical Technology, Inter American University of Puerto
Rico, Metropolitan Campus, San Juan, Puerto Rico. Email: [email protected]
Presented in poster format at the 2010 Latin American
Congress for the Treatment and Research in Multiple
Sclerosis (LACTRIMS), Santiago de Chile, Chile. Awarded the Víctor Rivera’s Prize for best research poster presentation.
Grant P20-RR016470 from the National Center funded
this research for Research Resources
a
INTRODUCTION
Multiple Sclerosis (MS) is considered a complex disease where genetic and environmental
factors have been implicated. Approximately
two million people worldwide and more than
400,000 persons in the United States are living
with MS. Generally, the onset of symptoms occurs in individuals from twenty to fifty years of
age, producing a progressive neurological dysfunction. The most common presenting symptoms are optic neuritis, diplopia, paresthesias,
fatigue, difficulties in motor coordination, and
cognitive dysfunction (1). The incidence and
prevalence of MS is higher in latitudes north
and south of the Equator (2, 3). In Puerto Rico
the estimated prevalence of MS is 42/100,000
habitants, according to the MS Epidemiological Study and more frequent in females than
in males with a ratio of 4:1, in contrast to the
prevalence reported by GEEMAL for Central
America and the Caribbean that range from
4.4 - 30/100,000 habitants (4, 5).
ABSTRACT
Multiple Sclerosis (MS) is a complex disease where genetic and environmental
factors have been implicated. The onset
of symptoms occurs in individuals from
twenty to fifty years of age, producing a
progressive impairment of motor, sensory
and cognitive functions. MS is more frequent in females than in males with a ratio of 4:1. The prevalence of the MS varies
among ethnics groups such as Europeans,
Africans and Caucasians. The estimated
prevalence of MS in Puerto Rico is 42 for
each 100,000 habitants, which is more
than the prevalence reported for Central
America and the Caribbean. In spite of this
prevalence, the genetic component of MS
has not been explored in order to know
the alleles’ expression of Puerto Rican MS
patients and compare it with the allele expression in other ethnic groups. Thirty-five
patients and 31 control subjects were genotyped. The allele frequencies expressed
in this sample were similar to those expressed for Puerto Ricans in the National
Marrow Donor Program Registry (n=3,149).
The most prevalent alleles for MS patients
were HLA-DRB1*01 and *03. HLA-DQB1*04
was the most frequent in the control group
and HLA-A*30, in MS patients. These findings are in agreement with published data.
HLA-DQB1*04 was a marginal protector
in this sample and this role has not been
described before. The accuracy of the results is limited due to the sample size. After
performing a statistical power analysis it
showed that by increasing the sample the
values would be significant.
Index words: HLA, alleles, genotyping, multiple, sclerosis, Puerto Rico
The exact cause of the disease is not known.
Studies analyzing brain necropsies of MS
patients; based on the animal model of the
disease - the Experimental Autoimmune Encephalitis- observing an increase of proinflammatory cytokines and a decrease in the activity
of regulatory T cells and by the identification
of antibodies produced against the components of the myelin in the cerebrospinal fluid
have demonstrated that the immune system is
a major player in the etiology of MS (6-9). MS
produces a severe demyelinization of the central nervous system, with axonal and neuronal
loss (10, 11).
The first reports of associations between
genetic markers and autoimmune diseases
were published in the 1960’s, identifying the
HLA locus as a critical region in the predisposition to the disease (12, 13). Several genes
have been associated to the genetic susceptibility. Such genes interactions, in addition to
environmental factors, could produce the inflammatory response that results in the CNS
white and gray matter lesions. Other genes
involved are TCR, IFN, VDR, TNF, IL-1, IL-2,
IL4R and, the APO4 allele, among others (14,
15). The development of new technologies
such as the genome-wide association studies
(GWAS) have provided an excellent approach
to understanding the relationship of several
genes by genotyping common known single
nucleotide polymorphisms (SNPs) from the
HapMap Project. A comparison between two
large groups is made and expressed in odds
ratio, based on the frequency of the alleles in
both groups. These studies have confirmed
16 loci with genome-wide significance. Several of the common risk variants are present
on genes involved in immunologic functions
and associated to autoimmune diseases (16).
Family studies have confirmed that susceptibility to MS is at least partly familiar (17). The
risk of MS occurrence in monozygotic twins
was 31%, whereas in dizygotic twin was only
5%. The risk of a sibling or a parent of an affected person was 3 to 4%, compared to the
risk of the general population of 0.1% (18).
Sadovnick (1996) showed that not all MS
patients express the HLA-DRB1*15 alleles
associated to MS (19). Studies performed in
other geographical regions showed that alleles described to be present in MS patients
were present in the vast majority of samples
analyzed; they also described differences in
allele expression in other ethnic groups and
geographical regions shown in Table 1: Diversity of HLA Alleles’ Expression in Multiple
Sclerosis.
HLA Class I and Class II alleles’ expression
of a group of Puerto Rican RRMS patients
and control subjects were analyzed and
compared findings to the HLA expression
published for other ethnic groups and geographical regions, in order to: 1) determine
their haplotype and see if it is similar to the
haplotypes described for other ethnic groups
and geographical regions, and 2) seeking for
presence of new specificities that could favor
a predisposition in developing MS in an attempt to understand the higher prevalence of
MS in Puerto Rico.
19
Table 1. Diversity of HLA alleles’ expression for MS patients in different geographical areas and ethnic groups on published
data.
MATERIAL AND METHODS
Patients and control subjects
Patients were recruited between May and November 2007 from a cohort of MS patients, undergoing follow up visit at the San Juan MS
Center. The data set comprised 35 patients diagnosed with definite remitting-relapsing multiple sclerosis (RRMS); self reported as Puerto
Ricans and after a neurologist evaluation, according to McDonald criteria (20) and once
evaluated and met the inclusion criteria. The
31 control subjects were individuals without a
definite MS diagnosis, inflammatory diseases
or malignancies; matched ethnically and geographically, for age, gender, and social background. They were recruited from other patients visiting the San Juan MS Center, clinical
laboratories, and university students. All study
participants were self-reported as Puerto Ricans. IRB approval and informed consent from
all study participants was obtained.
DNA sample collection
Two tubes of peripheral blood from patients
and controls were obtained by phlebotomy,
following the procedures established by accrediting agencies. DNA was extracted from
peripheral blood using commercial methods
(QIAamp, QIAGEN). DNA concentration was
adjusted to 20μg/μl with a purity of OD260/280
of 1.65 to 1.80. The DNA samples were kept
frozen at the PI laboratory, until mailed to the
National Human Genome Center at Howard
University, Washington, DC.
HLA Genotyping
MHC HLA Class I (HLA-A and B) and Class II
(HLA-DR and DQ) genotyping was performed
using a commercial kit (LABType SSO Typing Tests, One Lambda Co. LA, California).
HLA alleles’ detection was done using a nonradioactive PCR-SSOP (polymerase chain
reaction-based sequence specific oligonucleotide probe) reverse line-blot assay, and analyzed in a LABScan™100. Briefly, target DNA
was PCR-amplified using specific primers for
the HLA Class I (HLA-A and B) and Class II
(HLA-DR and DQ) locus. The PCR product
was denatured and allowed to rehybridize
to complementary DNA probes conjugated
to fluorescently coded microspheres. A flow
analyzer identified the fluorescent intensity of
phycoerythrin (PE) on each microsphere. The
assignment of the HLA typing was based on
the reaction pattern compared to patterns associated with published HLA gene sequences.
Statistical Analysis
An epidemiological profile of the participants
was performed using frequencies distributions
and descriptive statistics (mean, standard deviation, and percentiles). Graphs and Box plot
were used to better understand the similarities
and differences in the two study groups. To
describe the frequencies of the alleles by type
of participant (MS and control) a contingency
Table was utilized. To determine significance
difference among the alleles frequency by type
of participants, the odds ratio was estimated
with 95% confidence using a logistic regression model. In three loci some alleles had very
small frequency (<6), so they were grouped in
a category called “others” and this category
was taken as the reference group for computing odds ratio (OR).
RESULTS
Mean age of MS patients was 46.7 years. Females mean age was 46 years SD (9.7) and
males mean age was 49.3 years SD (9.4).
Female to male ratio was 4:1. Mean age of
control subjects was 34.6 years; females
mean age was 41 years SD (18.2) and male
mean age was 34.5 years SD (15.5). Female
to male ratio was 3.43:1 (see Table 2). Sixtysix individuals (35 MS patients and 31 control
subjects) were genotyped for HLA-A, HLA-B,
HLA-DRB1 and HLA-DQB1 locus. Allele frequencies were analyzed at a resolution corresponding to serological specificities and, compared to data for Puerto Ricans provided by
DNA data bank of the National Marrow Donor
Program (NMDP), in order to demonstrate that
alleles found in this research were representative of the Puerto Rican population.
Alleles’ frequencies
Seventeen different HLA-A alleles were observed in the samples genotyped: The most
frequent alleles were *02, *24 and *03. Twenty-six different HLA-B alleles were observed in
the samples genotyped: The most frequent alleles were *44, *35, *15, *41 and *08. Thirteen
different HLA-DRB1 alleles were observed in
the samples analyzed: The most frequent alleles were *13, *04, *03, *07 and *15. Five different alleles were observed in the samples
genotyped for HLA-DQB1 locus: The *03 allele
was the most frequently observed followed by
*02, *06, *05 and *04 (see Table 3).
HLA-A, HLA-B, HLA-DRB1, and HLADRB1 alleles’ frequencies and the
risk for MS
To determine whether the alleles expressed in
the study sample influenced the magnitude of
risk for MS, logistic regression was used to examine the effect of HLA-A, HLA-B, HLA-DRB1,
and HLA-DQB1 alleles compared to controls,
to yield odds ratios with 95% confidence intervals. For HLA-A, the results after the analysis
were: the OR for HLA-A *30 was 7.2 (95%CI:
.74, 70.2) times the odds of having MS in participants classified in the category “others”.
This excess was marginally significant (p-value=0.089). The rest of the alleles did not show
statistical evidence of significant increments
(P-value>0.1). For HLA-B, the results were:
the odds of having MS in participants with allele *15 was 3.17 (95%CI: 0.58, 17.15) times
the odds of having MS in participants classified
in the category “others”. However, this excess
was not significant (p-value=0.181). The odds
of having MS in participants with allele *35
20
Table 2. Epidemiological Data for MS Patients and Control Subjects.
Table 3. Most Frequent Alleles Express in Sample.
Table 4.
Summarizes
the most relevant findings of
the HLA genotyping MS patients as a function of Odds
Ratio (OR) and compare the
numbers to the roles given
by the researchers in other
ethnic groups.
21
was 1.35 (95%CI: .33, 5.55) times the odds of
having MS in participants classified in the category “others”. However, this excess was not
significant (p-value=0.671). The odds of having MS in participants with allele *41 was 1.20
(95%CI: 0.23, 6.09) times the odds of having
MS in participants classified in the category “others”. However, this excess was not significant
(p-value=0.821). The odds of having MS in participants with allele *44 was 0.75 (95%CI: 0.19,
2.87) times the odds of having MS in participants
classified in the category the “others”. However,
this reduction was not significant (p-value=0.697)
(see Table 4).
Some findings of this study are in agreement to
the findings published in literature. Smestad et al.
(2007) were not able to identify a significant contribution of the HLA-A alleles in association to the
clinical phenotypes of MS (21). This group, in an
unpublished data, observed that the presence of
HLA-A*02 decreased the risk of MS, significantly
(22).
DISCUSSION
In this study, most frequent allele observed in the
control group was HLA-A*02. This allele is also
frequent in the data provided by the NMDP. This
study also found that HLA-DRB1*01 was the most
represented allele in MS patients. DeLuca et al.
(2007) provided evidence that HLA-DRB1*01
is not a protective allele, as stated by other researchers (21, 23). This allele acts as an independent modifier of the disease progression because
they found that HLA-DRB1*01 was more frequent
in patients with benign multiple sclerosis than in
patients with the malignant form. Brynedal et al
(2007) and Barcellos et al. (2006), in two studies performed with Sweden, Sicilian and Spanish
families, the authors implicated the HLA-DRB1*03
allele in the risk of MS (24; 25). The HLA-DRB1*03
allele was the second most represented in MS
patients in the present study. Dean et al. (2007)
points to HLA-DRB1*03 and *04 alleles as influencing the risk of the disease in Malta. It is suggested that HLA-DRB1*03 may be involved in
MS as a secondary MS marker (26). The present
study found that HLA-DQB1*04 was the allele less
represented in MS patients. This allele might confer a protective role against the disease. This has
not been described before in literature as an allele
implicated in susceptibility or resistance to MS.
More studies should be done in the Puerto Rican
population to confirm these results, because the
95% confidence intervals were large.
Sixty-six samples from MS patients and control
subjects were successfully genotyped. Mean
age of MS patients and female to male ratio was
similar to results obtained in the Epidemiological
study conducted by the Puerto Rico MS Foundation (4). Analysis of data generated in present
study was performed at low resolution, in order
to compare the results to statistics for Puerto
Ricans, provided by the National Marrow Donor
Program. Most frequent alleles for HLA-A locus
were*02, *24 and *03; for HLA-B locus, most
frequent alleles were *44, *35, *15, *41 and *08;
for HLA-DRB1 locus, most frequent alleles were
*13, *04, *03, *07 and *15, and for HLA-DQB1
locus, *03 allele was most frequently observed,
followed by *02, *06, *05 and *04. Comparison
of alleles’ frequencies reported by the NMDP databank for Puerto Ricans and alleles expressed
in the control group of this study demonstrated
a correspondence of alleles expressed in both
groups for HLA-A, HLA-B and HLA-DRB1 locus.
This study represents the first genetic study performed with a group of MS patients in Puerto
Rico. The prevalence on the disease in Puerto
Rico is four times higher than numbers reported
for the Tropics by the MS International Federation (MSIF) and GEEMAL (5). Although the high
prevalence of MS; there is no information about
the genetics of the disease in Puerto Rico. Other
genetic studies in the Island have shown that rare
genetic conditions are more common in specific
regions of the Island than worldwide. It is necessary to perform more studies to determine the
relationship between HLA alleles, and the clinical presentations and severity of the disease.
This study results show the existence of alleles
that predispose and confer resistance to the
disease in the Puerto Rican MS patients, which
are statistically significant; others are marginally
significant due to the small size of the group. A
Statistical Power Analysis performed showed
that an increase in the sample number would.
In summary, there were not significant differences (p-value>0.05), the higher increments
were observed in the allele *15 with respect to
the category “others”. The odds of having MS in
participants with allele HLA-DRB1 *01 was 11.0
(95%CI: 1.1, 109.7) times the odds of having MS
in participants classified in the category “others”. This excess was statistically significant (pvalue=0.041). The odds of having MS in participants with allele *03 was 4.3 (95%CI: 0.97, 19.1)
times the odds of having MS in participants classified in the category “others”. This excess was
marginally significant (p-value=0.054). The rest
of the alleles did not showed statistical evidence
of significant increments (P-value>0.1). For HLADQB1, the results were: the odds of having MS
in participants with allele *04 was 0.23 (95%CI:
0.05, 1.09) lower than the odds of having MS
in participants with allele *02. This excess was
marginally significant (p-value=0.066). The rest
of the alleles did not show statistical evidence of
significant increments (P-value>0.1).
22
show the same results with a decrease in the CI
(see Table 5). The genetic profile of the Puerto
Rican population provides a unique model to
study the immunobiology of Multiple Sclerosis
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2nd ed. WB Saunders, 2003; Philadelphia, PA. 10601076.
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Corona T Roman, GC. Multiple Sclerosis in Latin
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Kurtzke JF. Epidemiology and Etiology of Multiple Sclerosis. Phys Med Rehabil Clin N Am. 2005;
16(2):327-349.
4. Chinea A, Pérez-Maldonado N, Pérez-Canabal
A. Clinical features of Multiple Sclerosis in Puerto Rico.
2012. NP.
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Melcon M, Melcon C, Bartoloni L et al. Towards establishing MS prevalence in Latin America and
the Caribbean. Mult Scler J. 2012; Vol. 0 (0):1-8.
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Chen SJ, Wang YL, Fan HC et al. Current status
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Kimura A, Kishimoto T. IL-6: regulator of Treg/
Th17 balance. Eur J Immunol. 2010; 40 (7):1830-5.
8.
Goverman JM. Immune tolerance in multiple
sclerosis. Immunol Rev. 2011; 241(1):228-40.
9.
Lourenco P, Shirani A, Saeedi J. et al. Oligoclonal bands and cerebrospinal fluid markers in multiple sclerosis: associations with disease course and progression.
Mult Scler. 2012; Sep 7. [Epub ahead of print].
10.
Hemmer B, Cepok S, Nessler S et al. Pathogenesis of multiple sclerosis: an update in immunology. Curr
Opin Neurol. 2002; 15 (3): 227-231.
11.
Dutta R, McDonough J, Yin X et al. Mitochondrial
dysfunction as a cause of axonal degeneration in multiple
sclerosis patients. Ann Neurol. 2006; 59 (3):478-89.
12.
Gourraud PA, Harbo HF, Hauser SL et al. The
genetics of multiple sclerosis: an up-to-date review. Imm
Rev. 2012; Vol. 248: 87-103.
13.
Alter M, Harshe M, Anderson VE et al. Genetic
association of multiple sclerosis and HL-A determinants.
Neurology 1976; 26(1):31-6.
14.
Favorova O, Favorov A, Boiko A et al. Three allele combination association with Multiple Sclerosis. BMC
Med Gen 2006; 7:63.
15. Sawcer S, Ban M, Maranian M et al. International Multiple Sclerosis Genetic Consortium. A High-Density
Screen for Linkage in Multiple Sclerosis. Am J Hum Genet
2005; 77:454-467.
16. Kemppinen A, Sawcer S, Compston. A Genomewide association studies in multiple sclerosis: lessonsand
future prospects. Brief Funct Genomics 2011; 10 (2):61-70.
17.
Sadovnick AD, Armstrong H, Rice GP et al. A
population-based study of multiple sclerosis in twins: update. Ann Neurol 1993; 33 (3):281-285.
18. Sadovnick AD, Baird PA, Ward RH. Multiple
sclerosis: updated risk for relatives. Am J Med Gen 1988;
(29):533-41.
19. Sadovnick AD. Genetic epidemiology of multiple
sclerosis: a survey. Ann Neurol 1996; 36 Suppl 2:S194203.
20.
McDonald WI, Compston A, Edan G et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 2001; 50 (1):121-127.
21.
Smestad C, Brynedal B, Jonasdottir G et al. The
impact of HLA-A and -DRB1 on age at onset, disease course
and severity in Scandinavian multiple sclerosis patients
23
. Eur J Neurol. 2007; 14(8):835-40.
22.
Bergamaschi L, Leone MA, Fasano ME et al.
HLA-class I markers and multiple sclerosis susceptibility in the Italian population, Genes Immun. 2010; 11(2):
173–180.
23.
DeLuca GC, Ramagopalan SV, Herrera BM et
al. An extreme of outcome strategy provides evidence
that multiple sclerosis severity is determined by alleles
at the HLA-DRB1 locus. Proc Natl Acad Sci USA 2007;
104(52):20896-901.
24.
Brynedal B, Duvefelt K, Jonasdottir G et al. HLAA Confers an HLA-DRB1 Independent Influence on the
Risk of multiple Sclerosis. PLoS One 2007; 2(7):e664.
25.
Barcellos LF, Sawcer S, Ramsay P et al. Heterogeneity at the HLA-DRB1 locus and risk for multiple
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Dean G, Yeo TW, Goris A et al. HLA-DRB1 and
multiple sclerosis in Malta. Neurology 2008; 70:101-105.
Acknowledgements
We thank Dr. Alicia Roe for critical reading of the manuscript and the National Marrow Donor Program (NMDP)
for providing data for Puerto Ricans.
RESUMEN
La Esclerosis Múltiple (EM) es una enfermedad
compleja en la que se implican factores genéticos y ambientales. Afecta a personas entre
las edades de 20 a 50 años, produciendo un
deterioro progresivo de las funciones motoras,
sensoriales y cognitivas. Es más frecuente en
mujeres a razón de 4:1. La prevalencia de la
EM varía en diferentes grupos: europeos, africanos o amerindios. Diferente a lo sucede en
América Central y el Caribe, que presentan una
prevalencia entre 5.5 a 30 casos por 100,000
habitantes, la prevalencia en PR se estima en
42/100,000 habitantes. A pesar de esta prevalencia, el componente genético no se había
explorado para conocer los alelos expresados en los puertorriqueños y compararlos con
otros grupos étnicos. Se hizo el genotipo de
35 pacientes con EM definitiva y a 31 sujetos
control. La frecuencia de los alelos presentes
en esta muestra fue similar a la frecuencia de
los puertorriqueños del registro del National
Marrow Donor Program (n=3,149). Los alelos
predominantes en pacientes con EM fueron el
HLA-DRB1*01 y *03. El alelo HLA-DQB1*04 predominó en los sujetos control y el HLA-A*30,
en pacientes con EM. Estos hallazgos concuerdan con los datos publicados. El alelo HLADQB1*04 fue marginalmente protector en esta
muestra y este rol no se había descrito anteriormente. La precisión de los resultados está
limitada por lo reducido de la muestra; sin embargo, el análisis de poder estadístico reflejó
que, al aumentar la muestra, los valores serán
significativos.
24
EIWA-III measures of
cognitive function in
young Puerto Rico
patients with epilepsy
Karla Narváez Pérez PhDa,b*, Leila Fernández
Crespo PhDa, María Teresa Miranda MDa,b, Frances Boulón Diaz PhDa
Inter-American University, Metropolitan Campus, San
Juan, Puerto Rico.
San Juan Bautista School of Medicine, Caguas, Puerto
Rico.
*Corresponding author: Karla Narváez PhD - Urb. Río
Hondo 1 Calle Río Cañas D-16 Bayamon P.R. 00961. Email: [email protected]
Presented in poster format at the 2012 Neuropsychology
Congress, San German, Puerto Rico.
a
b
INTRODUCTION
Epilepsy is a recurrent paroxysmal disorder of
cerebral function characterized by sudden brief
attacks of loss of consciousness, motor activity, sensory phenomena, psychic phenomena,
and inappropriate behavior as a result of excessive neuronal discharge (1). Epilepsy is the
most common chronic neurological disease effecting approximately 1% to 4% of the population over the life span (1). In the past, clinical
manifestations of seizure led to names of petite mal, grand mal, or psychomotor. Currently,
epileptic seizures are classified by correlation
of path physiological phenomena with clinical
features (1). There are two major divisions of
epileptic seizures: partial seizures and generalized seizures. In partial seizures, the abnormal electrical discharge is limited to one area of
the brain. Many parts of the brain are involved
in generalized seizures. Partial Seizures could
have complex partial seizures (psychomotor
or temporal lobe epilepsy), affect consciousness and originate from the temporal lobes of
the brain. These seizures are characterized by
automatisms, which are involuntary, repetitive
behaviors such as head turning and random
movement that is not remembered by the person after the seizure is over. The person may
appear dazed during the seizure and be unresponsive to others. Simple partial seizures
generally do not affect consciousness and are
the most common type of epilepsy. They may
cause sudden, jerking motions of the body and
affect vision or hearing.
ABSTRACT
Evaluation and measurement of intelligence contributes significantly to the
scientific endeavor of psychology as
a science. This study was exploratory
and descriptive, with twenty young patients with epilepsy from Puerto Rico of
ages between 16-20 years. Compared
the execution of a matched group of
the normative sample and the group
of adults 21 to 64 years with epilepsy
belonging to the standardization sample in Puerto Rico. The data was analyzed using descriptive and inferential
statistical calculations. Survey results
reflect significant differences in the
scores of the subtests that make up the
intelligence scale EIWA-III. In all measures, the group of participants with
epilepsy rate was lower than the reference group. The comparison of scores
on the subtests that measure executive
functions was analyzed by the working
memory index (WMI). Based on the data
obtained, the performance in executive
functions EIWA-III is significantly lower
in participants with epilepsy compared
to the reference groups. Analysis of
variance/ANOVA showed no significant differences between IQ scale for
implementation (F = 8.77) with a probability of 0.001, CI scale (F = 4.35) was
0.01 and verbal scale IQ (F = 2.67) was
0.05 for the group of young patients
from 16 to 20 years with epilepsy, their
IQ score compared with the normative
group on the subscales that comprise
the Verbal Scale, Performance and Total rates of IQ trial EIWA-III. In light of
these results, the statistically significant differences for each subscale: Verbal IQ, Performance, Total and indexes
EIWA-III, suggest that the level of intelligence of sample group, 16 to 20 years
old with epilepsy, was below average in
comparison with the normative group.
The results are consistent with the literature on cognitive neuropsychology
and performance of subjects with epileptic diseases.
Index words: measures, EIWA-III, cognitive, functions, young, Puerto Rico,
epilepsy
While generalized seizures we could have absence seizures (petit mal), typically occur in
childhood and are distinguishable by short periods (5-15 seconds) of staring, blinking, rolling
of the eyes, or arm movements. These brief
lapses of consciousness are followed by a return to full awareness. Tonic-clonic seizures
(grand mal) are characterized by a stiffening
of the body and jerking body movements. A
person sometimes loses consciousness during a tonic-clonic seizure and may also have
shallow breathing and a loss of bowel/bladder
control. The evaluation and measurement of
intelligence are tools used by professionals of
psychology to identify potential needs of individuals. The EIWA-III is a validated instrument
used for such purpose (2). Current studies
show differences in executive functions among
people with epilepsy when compared with normative samples of the tests used.
The concept of psychological measurement is
based on the interest of deepening the knowledge about human beings. This area of psychology is rooted in the need to understand
and analyze the intellectual and psychological
differences between individuals and different
reactions of the same persons. Psychology as
a science requires assessment, exploration,
control, and prediction of human behavior. The
development and management of assessment
instruments are relevant to psychological measurement. Psychologist evaluation instruments
used to obtain a more objective and accurate
measure of those cognitive skills or psychological traits of the individual being evaluated.
For the last twentieth century, the creation
and administration of psychological tests to
measure behavior patterns of persons have
experienced a significant increase in different
parts of the world. The development and use
of more objective tests to measure patterns of
human behavior is a phenomenon observed
with equal increase in Puerto Rico (2).
In Puerto Rico, there is no research on the
applicability, validity, and reliability of psychological measurement instruments (3). In turn,
this lack of research has promoted, according
to the authors, who for years have been using measurement instruments that respond to
a foreign culture, no information about its applicability to the Puerto Rican population. The
problem to study was to evaluate and compare
the Intelligence Quotient (IQ) obtained through
the test to measure intelligence based on
Wechsler Intelligence Scale for Adults (EIWAIII, 2008) for a group of young patients with epilepsy in Puerto Rico between the ages of 16 to
25
20 years using the standard set. Although the
test has been translated, adapted and standardized for Puerto Rico, it does not provide
data about its usefulness for differential diagnosis in young people with epilepsy between
the ages of 16 to 20 years to facilitate the work
of clinical and counseling Psychologist. In
Puerto Rico until 2008 the EIWA was used to
measure adult intelligence (4). However, due
to the specific problems generated by the use
of a foreign instrument it does not respond to
the socio-cultural context of the population in
which it is used, the Department of Psychology
at the Ponce School of Medicine carried out
the translation, adaptation, and standardization of EIWA-III for Puerto Rico.
Studies demonstrate that in the memory area
60% of the population with epilepsy has attention deficits. The literature indicated that individuals with epilepsy, whom are subject to
surgical treatment, tend to function poorly after
surgery (5). Intelligence levels of individuals
with epilepsy may vary according to the location of the epileptogenic focus (6). Also there
was a study conducted with epilepsy patients
between the ages of 21 to 64 years using the
EIWA-III, in order to evaluate the performance
of a sample of the Puerto Rican adult population (7). Studies indicate that there is an increased risk of cognitive impairment in relation
to the high doses of drugs aggravated when
using multiple medications to reduce seizures.
Once a treatment helps reduce or control epileptic seizures it is possible to demonstrate an
improvement in cognitive functions. The localization of epileptic discharges has been identified as another factor that can affect cognition in people diagnosed with epilepsy. It has
been documented that people with epilepsy in
the left lobe neuropsychological suffer greater
problems than those with right lobe epilepsy.
For example, the temporal lobe epilepsy (TLE)
has been associated with attention problems,
memory deficit and learning disabilities also
present in a significantly higher frequency.
Still, trends have emerged across the various
functional domains including intelligence, attention, and executive functioning, language
and memory (8).
Research in psychology serves to renew, improve the teaching-learning strategies and,
in turn, improve the development of the persons targeted by the occupation. The present
study analyze and compare the intellectual
functioning youth group with epilepsy between
the ages of 16 to 20 years, with the group of
21-64 years and the normative group on Adult
Intelligence Scale-Wechsler-III. This study
took into account the absence of clinical instruments for the assessment of intelligence
in people with this neurological disorder in the
Puerto Rican population. The results of this
research meet the study objectives stated in
terms of knowing the IQ, verbal, performance
and total executive functions, mean, and standard deviation in a sample of participants in
an age group between 16 at 20 years, which
provided information about the measurement
of intelligence. The results are consonant with
the purpose that involves evaluative metering
in terms of intelligence tests used to determine
IQ, cognitive functioning in academic settings
as well as the determination of financial assistance under the Federal Americans with Disabilities Act PL110-325 (ADA, 1990) stipulated.
These findings will be useful because they provide and add data to the meter depending on
the age group of clinical populations (epilepsy) not investigated at the time to adjust and
normalize EIWA-III in the adult population of
Puerto Rico (9).
Through the years there is a clear need for
measurement instruments that are valid and
reliable for a full and proper assessment of
the population of Puerto Rico, according to the
terms (10). According to the authors, the lack
of research on the applicability, validity, and reliability of psychological measurement instruments used in Puerto Rico is evident. Through
this study, we proposed an analysis of the differences in IQ of people with epilepsy condition, to be compared with the matched sample
policy group in EIWA-III (Pearson, 2008) and
youth Puerto Ricans between the ages of 16
to 20 years. The information obtained through
this research provides the possibility to measure and identify youth’s between the ages
of interest and compares their performance
with the results of the tests administered to
the normative sample EIWA-III. Therefore, the
professional practice of psychologists as educating professionals has an instrument that includes the youth population between ages 16
to 20 years with epilepsy in Puerto Rico. As
a result, provides objective evidence on Scale
Wechsler Adult Intelligence-III from the sample
population analyzed, which contributed with
useful, relevant, timely, and also contributed to
knowledge advancement, literature and scientific work in the island. Other studies found that
the location, the age of the onset and dominance are the best predictors of the scores for
the scales of Total, Verbal, and Performance.
It was also found that the longer a person had
the condition, the lower the score on the WAISR
and those patients with more education scored
more stable than the rest of the participants
(11). Different epilepsy drugs bring different
cognitive risks such as slowness in processing
information and disturbances such as anomie
and dysphasia (12 and 13). It was also reported that the older the person has the condition;
their performance on the WAIS III tends to be
significantly lower than expected. They also
found that people with epilepsy with lower levels of education tend to perform more poorly in
the test (14)
Based on the literature, the results of this study
will generate new approaches, theories, and
the development of tools for mediation through
the application of the scientific method. The
results of this research in the field of epilepsy
were the basis for expanding knowledge, measuring performance of young people with epilepsy in Puerto Rico, and the benefit of future
researchers with updated information about
the variables related to the condition of epilepsy. These results are useful because they
provide the basis for further studies in the future; develop possible avenues of intervention
and support for persons with epilepsy from the
educational reality of Puerto Rico. In light of
the results, psychologists and other health professionals can plan new intervention programs
for persons with epilepsy and improve their
treatment practices at the end of strengthening
the quality of human life with the condition of
epilepsy (15-17).
METHODS
For the purpose of this study, a quantitative
nature exploratory/descriptive research design
was selected. From the exploratory design
perspective it provided the flexibility to analyze
and discover new information about the phenomenon of the variable under investigation.
It allowed establishing quantitatively possible
relationships or contrasts between the study
variables. From a descriptive perspective, it allowed for an accurate description of the phenomenon of the analyzed variable, which is to
prevent the results from being flawed (18). The
purpose of using this design responded to the
interest of having to explore, introduce and describe the possible differences in performance
IQ of young subjects with epilepsy compared
to the group of 21-64 years and the normative
group.
The target population to participate in this
study were young Puerto Ricans between
26
the ages of 16 to 20 years residing in Puerto
Rico who had been diagnosed the condition of
epilepsy. Among this population, the sample of
participants was selected by combining techniques and availability intentional given the accessibility of participants (18). Therefore, the
intentional selection of participants responded
to the following specific inclusion criteria: 1)
have documented diagnosis of epilepsy such
as: partial seizures or generalized seizures, 2)
be under drug treatment for epilepsy condition
and have controlled crises with medication, 3)
being between the ages of 16 to 20 years, 4)
have resided in Puerto Rico most of their life
or for a minimum of 10 years. The Institutional
Review Board of the Inter-American University
of Puerto Rico approved this research in 2011.
Participation was voluntary and placed a call
for subject’s recruiting in a few neurologists’
office in the San Juan metropolitan area. The
participation of each person, who met the inclusion criteria, was limited, freely and voluntary,
avoiding pressure or force to participate in the
study. On the other hand, the following exclusion criteria was set: 1) persons not diagnosed
with a condition of epilepsy, 2) persons under
16 and over 20 years, 3) persons who have
or had a history of the following conditions:
Specific Learning Problems, Attention Deficit,
Mental Retardation, Sensory or Occupational
Problems, Alzheimer’s, Parkinson’s, Multiple
Sclerosis or Muscular Dystrophy, and 4) persons who were not residents of Puerto Rico or
had less than 10 years residing in the island.
Moreover, the youth group of 16-20 years with
epilepsy was compared with the normalized
group EIWA-III test for Puerto Rico and the
panel study of adults with epilepsy between
21-64 years. One group included 30 Puerto
Rican adults ages 21-64 years diagnosed with
epilepsy. The other group included a total of
330 heterogeneous persons that consisted of
adolescents, young adults and Puerto Ricans
who did not have any condition.
The research instrument used was the
Wechsler Intelligence Scale for Adults, tailored
and standardized for Puerto Rico (EIWA-III).
Data collected through the research process
was tabulated including analysis of average,
standard deviation (s), the simple analysis
of variance and analysis of Student-t-test to
establish differences and comparisons. The
simple analysis of variance / ANOVA (F) was
used to compare the values of a set of numerical data to determine whether they were significantly different from the values of other data
sets. The analysis of variance / ANOVA was
used to associate probability to the conclusion
that the average of a set of scores is different
from the mean scores of the other group. The
Student-t-test was used to compare the performance of participants in terms of the total
scores of the scales Verbal, and Total Execution. In addition the mean and standard deviation for the total scale, performance scale and
verbal scale was calculated.
RESULTS
Total participants were 20, ten male and 10 female. All were residents of the San Juan metropolitan area of Puerto Rico. Educational level
of parents ranged from high school graduates
to higher education (45% of parents had completed high school and 55% had college education). Average annual household income was
$ 25,000. Eleven participants had a diagnosis
of partial epilepsy and nine had a diagnosis of
generalized epilepsy. The reported mean age
of onset of seizures was 11 years. In 40% of
the participants, the seizure frequency was less
than 2 times per month and 60% reported a frequency of less than 2 times per year. The reference group in the standard set of the test using
the same age and the group of 21 to 64 years
was the comparison study (5). Refer to Graph 1
and Graph 2.
Analysis of Total Intelligence Quotient (CIT) includes the contrast of the results on the scales
of Verbal IQ and Performance by Puerto Rican
youth group of 16 to 20 years, the adult group
and the normative group. These results show
that there are significant differences between
the reference groups. In light of the results, the
statistically significant differences for IC Implementation Scale (F = 8.77) was with a probability of .001, Scale IQ score (F = 4.35) was .01,
and the scale Verbal IQ (F = 2.67) was 0.05. To
this effect, highlights of the responses significantly between reference groups vary and are
different to Total IQ measure. Refer to Table 1
and Graph 3 for details.
The results evidenced through ANOVA analysis
established that there are statistically significant
differences between rates of verbal comprehension (VC), Perceptual Organization (PO),
working memory (WM) and processing speed
(PS) when comparing scores between executive functioning groups under study. Specifically, WM Index scores (F =5.81) and VP Index
(F =-11.66) showed statistically significant difference of .001. Indices CV (F =1.20 and OP
(F =3.039) .05 showed significant differences.
Based on these data, it is stated that comparison groups for the performance behavior
27
of executive functions in EIWA-III
testis significantly different. Refer
to Table 2 and Graph 4 for details.
DISCUSSION
The research problem was to
evaluate and compare the IQ, obtained through the EIWA-III of a
group of young Puerto Rican epilepsy between the ages of 16-20
years, the second group of 21 to
64 years and the third group the
standard set. Analysis of variance
/ ANOVA showed that there was
a significant difference between
the group of young Puerto Rican
s from 16 to 20 years with epilepsy when compared to their score
in IQ, with the normative group
without the condition, in scales
of theVerbal Scale, Performance,
and Total IQ indexes on EIWAIII test. The apparent differences
between groups arise that the
pattern of performance of Puerto
Rican youths 16 to 20 years with
epilepsy differs from the pattern of
performance of the two comparison groups: the group of adults 21
to 64 years and EIWA-III normative group-III in each subtest included in the verbal scale, Implementation of Total IQ and Index.
The analysis shows that apparently Puerto Rican youth 16 to 20
years of age with epilepsy do not
respond to the same rules as the
two comparison groups (group of
adults 21 to 64 years with epilepsy
28
and without epilepsy normative group).
The group of young people 16 to 20 years
with epilepsy scored lower average scores in
IQ, compared to the average of the two test
groups EIWA-III. Similarly, in Verbal IQ and
Performance IQ and Total IQ, as well as in
the subscales of Verbal Comprehension Index, Perceptual Organization Index, Working
Memory Index and Processing Speed Index
Scale Indexes. The difference in the pattern
of performance demonstrated that the Puerto
Rican youth among the ages of 16 to 20 years
with epilepsy, when compared to the other
two groups, suggests that both groups are not
representative of the typical characteristics of
this group of young persons, given that, they
detract predictive test and its components according to the scientific perspective and literature (18, 19).
CONCLUSION
Epilepsy is associated more with cognitive
dysfunction in persons with early onset of the
condition, suffering from multiple episodes, requiring treatment with multiple drugs to control
their epilepsy condition and is secondary to
neuropathy. Persons with idiopathic epilepsy,
that have no neurological or are without any.
29
other neurological or psychiatric conditions,
often have normal intelligence (19) Many of
the studies reported in the literature are based
on samples from patients with severe epileptic conditions that fail to control the symptoms with harmless medication and sometime
even require surgery to contain their seizures
(20). The sample of person with epilepsy selected for the study of cognitive functioning in
EIWA-III are relatively mild clinical profiles in
that their epilepsy and was kept under control by pharmacological treatment. The operation of the sample in the test was within normal to low, even when compared to a group
that matched in age, gender and educational
level. The study confirms that a high proportion of persons with epilepsy achieve normal
intellectual development to low and maintain
cognitive function as long as their condition is
under control. However, it identifies differences between groups that are not significant but
have relevance to clinical work and reflecting
the sensitivity of EIWA-III. Lower scores were
found in the group of young people with epilepsy in the index associated with executive
functions of working memory and processing
speed, and the perceptual organization index.
Therefore, the information obtained from the
sample of people with epilepsy in Puerto Rico
reveals the need to conduct more specific research with larger samples and segmented
based on types of epilepsy. Further studies
would be useful to include measures of neuropsychological functioning. Future research
could correlate the functioning of people with
epilepsy in measures of intelligence and neuropsychological functioning, especially executive functions. The assessment of executive
functions has been one of the areas of interest
in the evaluation of people with epilepsy and
other neurological disorders. It was also one
of the most studied neuropsychological functions with groups of people with epilepsy. The
EIWA-III provides data on a number of executive functions including working memory and
processing speed. The correlation between
these neuropsychological measures of executive functions would be another type of study
relevant to the understanding of cognitive factors that affect this population.
30
REFERENCES
RESUMEN
1. Annegers, J. Epidemiology of epilepsy. In e. Wylie (Ed.).
The treatment of epilepsy: Principles and Practice 3rd.ed.
2001; Philadelphia: Lippincott, Williams, & Wilkins.
2. Pons, J., Flores, L., Matías, L., et al. Confiabilidad de
la Escala de Inteligencia Wechsler para Adultos Versión
III, Puerto Rico (EIWA-III). Revista Puertorriqueña de Psicología, 2008; 19: 16-26.
3. Laguer, A., Matías, L., Pons, J., et al. Ejecución de una
muestra de personas con diagnóstico de epilepsia en la
Escala de Inteligencia Wechsler para Adultos Versión III
(EIWA-III), normalizada para Puerto Rico. Revista Puertorriqueña de Psicología, 2008; 19: 1-15.
4. Wechsler, D. Manual for the Wechsler Adult Intelligence
Scale. 3rd ed. 1997; Technical Manual. San Antonio, TX:
The Psychological Corporation.
5. Chelune, G. J., Naugle, R. L., Lüders, H., et al. Individual change after epilepsy surgery: Practice effects and
base-rate information Neuropsychology, 1993; 7: 41-52.
6. Guerrero, D., Infante, Y., Palacios, X. Epilepsia: Personalidad, Depresión, Atención y Memoria. Repertorio de
Medicina y Cirugía, 2008; 17 (3): 156-167.
7. Rodríguez, J., Herrans, L., Pons, J., et al. Proceso de traducción y adaptación para Puerto Rico de Wechsler Adult
Inteligence Scale-III: Escala de Inteligencia Wechsler para
Adultos, versión III (EIWA-III). Revista Puertorriqueña de
Psicología, 2008; 19: 58-74Aldenkamp, A. R, & Bodde, N.
Behaviour, cognition and epilepsy. Acta Neurológica Scandinávica, 2005; 112: 19-25.
8. Lezak, M. D., Howieson, D. B., & Loring, D. W. Neuropsychological Assessment 4th ed. 2004; New York: Oxford
University Press.
9. Díaz, W. Diferencias en las puntuaciones del EIWA por
grupos diagnóstico esquizofrénicos, epilépticos y normales. 1972; Tesis inédita de maestría, Departamento de
Psicología. Universidad de Puerto Rico, Río Piedras.
10. Anastasi, A. y Urbina, S. Test psicológicos. 7ma
ed.1998; México: Prentice Hall.
11. Strauss, E., Hunter, M. & Wada, J. Risk factors for cognitive impairment in epilepsy. Neuropsychology, 1995; 9,
(4): 457-463.
12. Bennet, T. L. Cognitive effects of epilepsy and anticonvulsant medication. In T. L. Bennet (Ed.) The neuropsychology of epilepsy, 1992; (pp. 73-95) New York: Plenum
Press.
13. Aldenkamp, A. R, & Bodde, N. Behaviour, cognition
and epilepsy. Acta Neurologica Scandinavica, 2005; 112:
19-25.
14. Oyegbile, T. O., Bhattacharya, A., Seidenberg, M. &
Hermann, B. P. Quantitative MRI biomarkers of cognitive
morbidity in temporal lobe epilepsy. Epilepsia, 2006; 47:
143-152.
15. Lee, P. & Clason, C. Classification of seizure disorder and syndromes, and neuropsychological impairment
in adults with epilepsy. In a Morgan, J. & Ricker, J. (Eds).
2008; Textbook of clinical Neuropsychology (pp.437-465).
New York: Taylor & Francis.
16. Lee, S., Sziklas, V., Andermann, F., et al. The effects
of adjuvant topiramate on cognitive function in patients
with epilepsy. Epilepsy, 2003; 44(3): 339-347.
17. Meador, K. Cognitive outcomes and predictive factors
in epilepsy. Neurology, 2002; 58 (5): S21-S26.
18. Villanueve, M. Manual de práctica. Desarrollo de
destrezas básicas de investigación. 2004; San Juan.
Puerto Rico. Autora.
19. Dodrill, C. Progressive cognitive decline in adolescents
and adults with epilepsy. Progress in Brain Research,
2002; 135: 399-407.
20. Jensen, I. Temporal lobe epilepsy: types of seizures,
age, and surgical results. Epilepsia.1999; 53(5): 335–357.
La evaluación y medición de la inteligencia aporta significativamente al quehacer científico de la psicología como
ciencia. Este estudio fue exploratorio y
descriptivo, realizado en veinte jóvenes
puertorriqueños con epilepsia, entre las
edades de 16 a 20 años. Se compararon
con la ejecución de un grupo pareado
de la muestra normativa y el grupo de
adultos de 21 a 64 años con epilepsia,
pertenecientes a la muestra de estandarización en Puerto Rico. Los datos obtenidos se analizaron mediante cálculos
estadísticos descriptivos e inferenciales. Los resultados del estudio reflejan
diferencias significativas en las puntuaciones de las subpruebas que componen la escala de inteligencia EIWA-III.
En todas las medidas, el grupo de participantes con epilepsia obtuvo una tasa
inferior a la del grupo de referencia. La
comparación de las puntuaciones en
las subpruebas que miden funciones
ejecutivas fue analizada por el índice de
memoria de trabajo (WMI). Basándose
en los datos obtenidos, el rendimiento
en las funciones ejecutivas EIWA-III es
significativamente menor en los participantes con epilepsia, en comparación
con los grupos de referencia. El análisis
de varianza/ANOVA mostró que no había
diferencias significativas entre el CI de
escala para la implementación (F = 8,77)
con una probabilidad de 0.001, escala CI
(F = 4,35) fue de 0,01 y la escala verbal IQ
(F = 2,67) 0,05 para el grupo de jóvenes
puertorriqueños de 16 a 20 años con epilepsia, al comparar su puntuación de CI
con el grupo normativo en las subescalas que componen la Escala verbal, Ejecución e índices totales de CI en EIWA-III
de ensayo. A la luz de estos resultados,
las diferencias estadísticamente significativas para cada sub-escala: CI verbal,
Performance, Total e índices en EIWA-III,
lo que sugiere que el nivel de inteligencia del grupo de jóvenes puertorriqueños de 16 a 20 años con epilepsia era
menor de la media en comparación con
el grupo pareado de la muestra normativa. Los resultados obtenidos están en
consonancia con la literatura acerca de
la neuropsicología cognitiva y el rendimiento de las personas con enfermedades epilépticas.
31
32
Prenatal diagnosis of
a vein of Galen
aneurysmal
malformation using
color Doppler
ultrasound:
A case report
Ronald López-Cepero MDa*, Alberto de la Vega
MDa, Lauren Lynch MDa
a
Case Reports / Reporte de Casos
ABSTRACT
Vein of Galen aneurysms are a rare and
complex vascular malformation of the
brain. Their prevalence is somewhat less
than 1 in 25,000 deliveries. Common associated anomalies include ventriculomegaly,
cardiomegaly secondary to high cardiac
output and enlarged neck vessels, the later
being an almost pathognomonic sign. The
prognosis for these neonates is poor with
a mortality rate of 50% and a high risk for
neurologic sequelae. Color flow Doppler
studies of the fetal brain vasculature are a
reliable method for diagnostic purposes. In
this paper we present a case of a vein of
Galen malformation diagnosed prenatally
at 33 weeks of gestation using both 2D and
color Doppler ultrasound modalities.
Index words: prenatal, diagnosis, vein, Galen, aneurysmal, malformation, ultrasound,
Doppler
INTRODUCTION
Case History
Vein of Galen aneurysms are a rare and complex vascular malformation of the brain. Their
prevalence is somewhat less than 1 in 25,000
deliveries (1,2). These anomalies are characterized by various arteriovenous anastomoses
that drain into a main venous region. This region is not in fact the vein of Galen, but the median prosencephalic vein of Markowski, its embryonic precursor (3). The exact embryological
origin and development of this congenital malformation remains uncertain (4). Common associated anomalies include ventriculomegaly,
cardiomegaly secondary to high cardiac output
and enlarged neck vessels, the later being an
almost pathognomonic sign (5). The prognosis for these neonates is poor with a mortality rate of 50% and a high risk for neurologic
sequelae (6,7). Differential diagnosis has been
thoroughly described, including choroid plexus
cysts, pineal tumors, choroid papillomas and
intracerebral hematomas, among many others (8). Color flow Doppler studies of the fetal brain vasculature are a reliable method for
diagnostic purposes (9,10). In this paper we
present a case of a vein of Galen malformation
diagnosed prenatally at 33 weeks of gestation
using both 2D and color Doppler ultrasound
modalities.
A 31-year-old woman, gravida 4, para 3 with an
otherwise uncomplicated and uneventful pregnancy was referred to our maternal-fetal unit
at 32 weeks for sonographic evaluation due
to suspected hydrocephaly based on a previous sonographic study. We found a singleton male fetus in cephalic position with huge
anomalous vessels within the fetal brain showing marked turbulent flow on color Doppler sonography (Voluson 730 Pro with variable frequency curvilinear transducers) (see Figure 1).
The course of these vessels and their location
were consistent with an aneurysm of the vein
of Galen. Enlargement along with a tortuous
course of the neck arterial vessels was prominent and is shown in Figure 2. There was also
secondary obstructive hydrocephalus caused
by impeded drainage. The lateral ventricular
diameter was 2.2 cm (normal values should be
less than 1.2 cm). Cardiomegaly was present
secondary to the high output caused by this
vascular malformation. There was a normal
amount of amniotic fluid and the placenta was
located in the anterior uterine wall. The estimated fetal weight at the time of evaluation
was 2,188 grams consistent with the70th percentile for this gestational age. The couple was
counseled regarding the variable prognosis
Figure 1: Anomalous vessel within the fetal brain showing marked turbulent flow seen
on color Doppler sonography (Voluson 730 Pro with variable frequency curvilinear transducer).
Figure 2: Enlarged and tortuous neck arterial vessels
33
of this condition and the importance of being
managed at a supra-tertiary hospital. The diagnosis was confirmed after birth.
DISCUSSION
Vein of Galen aneurysmal malformations
(VGAM) are non-hereditary vascular brain disorders that comprise approximately 1% of all
congenital arteriovenous malformations (11,
12). As described by Gailloudet al, the actual
name of Vein of Galen is a misnomer, since
the true nature of this anomaly relies in a vascular system of multiple vessels draining into
a venous collector region, which corresponds
to the embryonic prosencephalic vein of Markowski (1). In this case we document the prenatal diagnosis of a vein of Galen malformation diagnosed at 32 weeks of gestation using
color Doppler flow ultrasound.
Sepulveda et al, described the most common
associated sonographic findings in prenatally
diagnosed cases of VGAM, which include cardiomegaly, enlarged neck vessels, ventriculomegaly and polyhydramnios, among others
(5). In their case series, cardiomegaly was
present in 64% of the cases suggesting that it
constituted a warning sign since etiology was
cardiac failure. In this case, cardiomegaly was
present in association with a large size vascular
cerebral lesion consistent with a poorer prognosis. We concluded that the finding of ventriculomegaly was related to impeded drainage at the level of either the aqueduct or the
posterior fossa fourth ventricle, probably due
to the size of the vascular lesion. A mass effect
as the sole cause for ventricular enlargement
has been challenged by Sepulveda et al. suggesting that abnormalities in the cerebrospinal
fluid flow may play a role in the etiology hydrocephalus, rather than purely a compression
effect. Enlarged neck vessels are an almost
pathognomonic finding and may signal worsening systemic tissue oxygenation (13,14). In
view of these findings, the presented images
are pathognomonic of a VGAM.
The differential diagnosis of such an abnormality includes primarily cystic lesions of the
fetal cerebral tissue. Modern obstetrical sonographic techniques have made prenatal
diagnosis of cerebral vascular abnormalities
easier. Color flow Doppler images provide
a reliable method for diagnosis showing bidirectional turbulent flow (15). This modality
allows us to differentiate among other nonvascular lesions of the brain such as porencephalic cysts and hydrocephaly (16).
2D ultrasonography of a VGAM frequently
shows an anechoic extra-parechymal lesion
located in the cerebral mid-line region (see
Figure 3); however, hyper-echogenic regions
might be seen if clots are formed within it. Different imaging modalities, like magnetic resonance, are currently being used for antenatal
assessment of fetal congenital anomalies, especially those of the brain. Nonetheless, the
main advantage of using MRIs is mainly in differentiating between intra and extra parenchymal arteriovenous malformations (17). More
studies are needed to conclude as to the utility
of this modality.
The antenatal diagnosis of a VGAM renders
the opportunity for an evaluation of a multidisciplinary team before delivering. The early
diagnosis of this malformation permits a neonatal and neurosurgical team assessment of
the fetus in utero and avoidance of late postnatal diagnosis, which could result in fatal consequences. If no signs of fetal cardiac insufficiency are evident, elective vaginal delivery at
a tertiary care center is suggested.
REFERENCES
1. Gailloud P, O’Riordan DP, Burger I, Levrier O, Jallo G, Tamargo
RJ et al.
Diagnosis and management of vein of Galen aneurysmal malformations.
J Perinatol 2005; 25:542-551.
2. Lasjaunias P, Hui F, Zerah M, Garcia-Monaco R, Malherbe V,
Rodesch G et
al. Cerebral arteriovenous malformations in children. Management of
179 consecutive cases and review of the literature. Childs Nerv
Syst 1995; 11:66-79.
3. Raybaud CA, Strother CM. Persisting abnormal embryonic
vessels in
intracranial arteriovenous malformations. Acta Radiol Suppl 1986;
369:
136-138.
4. Mullan S, Mojtahedi S, Johnson DL, Macdonald RL. Embryological basis of
some aspects of cerebral vascular fistulas and malformations. J
Neurosurg 1996; 85:1-8.
5. Sepulveda W, Plat CC, Fisk NM. Prenatal diagnosis of cerebral
arteriovenous malformations using color Doppler ultrasonography: case report and review of the literature. Ultrasound Obstet
Gynecol 1996; 6: 282-286.
6. Chevret L, Durand P, Alvarez H, Lambert V, Caeymax L,
Rodesch G et al.
Severe cardiac failure in newborns with VGAM. Prognosis significance of hemodynamic parameters in neonates presenting with
severe heart failure owing to vein of Galen arteriovenous malformation. Intensive Care Med 2002 ; 28:1126-1130.
7. Jones BV, Ball WS, Tomsick TA, Millard J, Crone KR. Vein of
Galen
aneurysmal malformation: diagnosis and treatment of 13 children
with extended clinical follow-up. Am J Neuroradiol 2002; 23:17171724.
8. Jeanty P, Kepple D, Roussis P, Shah D. In utero detection of
cardiac failure
from an aneurysm of the vein of Galen. Am J Obstet Gynecol
1990; 163:50-51.
9. Evans AJ, Twinning, P. Case report: in utero diagnosis of a vein
of Galen
aneurysm using color flow Doppler. Clin Radiol 1991 ; 44:281282.
34
Figure 3: 2D ultrasonography showing an anechoic extra-parencgymal lesion located in the cerebral mid-line region. 10. Ballester MJ, Raga F, Serra-Serra V, Bonilla-Musoles F. Early
prenatal
diagnosis of an ominous of the vein of Galen by color Doppler
ultrasound. Acta Obstet Gynecol Scand 1994; 73:592-595.
11. Comstock CH, Kirk JS. Arteriovenous malformations. Locations and
evolution in the fetal brain. J Ultrasound Med 1991; 10:361-365.
12. Maheut J, Santini JJ, Barthez MA, Billard C. Symptomatologie
Clinique de
l’anévrysme de l’ampoule de Galien. Résultats d’une enquête
nationale.
Neurochirurgie 1987; 33:285-290.
13. Koven M, Cohen HL, Goldman MA. Fetal intracranial AVM
presenting as
enlarged cardiac chamber. J Ultrasound Med 1992; 12:177.
14. Lee W, Kirk JS, Pryde P, Romero R, Qureshi F. Atypical presentation of
fetal arteriovenous malformation. J Ultrasound Med 1994; 13:645647.
15. Ishimatsu J, Yoshimura O, Tetsuou M, Hamada T. Evaluation
of an
aneurysm of the vein of Galen in utero by pulsed and color Doppler ultrasonography. Am J Obstet Gynecol 1991; 164:743-744.
16. Pilu G, Falco P, Perolo A, Sandri F, Cocchi G, Ancora G et al.
Differential
diagnosis and outcomes of fetal intracranial hypoechoic lesions:
report of 21 cases. Ultrasound Obstet Gynecol 1997; 9:229-236.
17. Beucher G, Fossey C, Belloy F, Richter B, Herlicoviez M,
Dreyfus M.
Diagnostic anténatal et prise en charge d’un anévrysme de la veine de Galien. J Gynecol Obstet Biol Reprod 2005; 34:613-619.
35
RESUMEN
El aneurisma de la vena de Galeno es una
malformación arteriovenosa del cerebro
rara y compleja. La prevalencia de la misma es alrededor de 1 entre 25,000 recién
nacidos. Entre los hallazgos más comunes
se encuentra la ventriculomegalia, la cardiomegalia secundaria al fallo cardiaco y
el agrandamiento de los vasos sanguíneos
del cuello, siendo este último un signo
casi patognomónico de esta identidad. El
pronóstico de estos neonatos es muy pobre y la secuela de defectos neurológicos
muy alta. El estudio con ultrasonido Doppler de color de la vasculatura del cerebro durante el período prenatal permite un
diagnóstico certero de esta malformación.
Se presenta el caso del diagnóstico a las
33 semanas de gestación de una vena de
Galeno utilizando 2D y color Doppler como
métodos diagnósticos.
36
Chorioangioma:
An uncommon cause of
hydramnios and
consequent preterm
labor in second
trimester of pregnancy
Gianni Rodríguez-Ayala MDa*, Alberto de la
Vega MDa, María Correa-Rivas MDb, Alexandra
Jímenez MDb
Puerto Rico-School of Medicine, San Juan PR
b
Department of Pathology and Laboratory Medicine, University of Puerto Rico-School of Medicine, San Juan PR
*Corresponding Author: Gianni Rodríguez-Ayala MD Ob-Gyn Residency Program, University of Puerto Rico
SOM, San Juan, Puerto Rico, 00936. E-mail: grodz08@
gmail.com
a
INTRODUCTION
Placental chorioangiomas are relatively common benign placental tumors occurring with an
incidence of approximately 1% of histologically
studied placentas (1). However, they show
clinical manifestations in only approximately 1
in 9,000 to 1 in 50,000 pregnancies (2). These
lesions have a close resemblance to the blood
vessels and stroma of the chorionic villi. Their
etiology is unknown but there is a strong relationship with gestations occurring at high altitudes, suggesting that hypoxia induced vascular growth factors may be involved (4).
We report a case of a large placental chorioangioma that produced fetal and maternal complications soon after its initial clinical presentation.
Case History
This is a case of a 25 years old female patient
P0A1 with 264/7 weeks of gestation confirmed
by a first trimester ultrasound. The patient had
no history of systemic illnesses. She smoked
since age 15 approximately one pack per week
but had quit during the early first trimester. Her
prenatal care was unremarkable except for a
borderline elevated maternal serum alpha-fetoprotein of 1.99 MOM done at 175/7 weeks
of gestation. A level II obstetric ultrasound performed at 19 weeks was reported negative for
ABSTRACT
Placental chorioangiomas are relatively
common benign placental tumors occurring with an incidence of approximately 1%
of histologically studied placentas. However, they show clinical manifestations in
very rare pregnancies usually at a median
gestational age of 28 weeks. Our report
presents an interesting and rare case of severe hydramnios with consequent preterm
labor and delivery in the second trimester
leading to neonatal death due to placental
chorioangioma. An earlier diagnosis could
have led to closer monitoring and prevention of the development of severe hydramnios with resultant preterm labor.
Index words: chorioangioma, hydramnios,
preterm , labor, pregnancy
fetal or placental anomalies and identified a
normal amniotic fluid volume.
The patient had an uneventful pregnancy until
253/7 weeks of gestation when she presented
with a bloody vaginal discharge not associated to pelvic pain. She eventually developed
pelvic pain and continued bloody discharge
for which she was admitted at a regional hospital for management of preterm labor. While
there, she was treated with magnesium sulfate
and single doses of terbutaline and nifedipine
for tocolysis. After receiving 24 hours of magnesium and two doses of betamethasone 24
hours apart she was discharged home as asymptomatic with a closed cervix.
The patient returned to the hospital the next
day with recurrent symptoms and was found
with a pelvic exam of 3 cm dilatation and 90%
effacement. She was again admitted with a
diagnosis of preterm labor. On sonographic
examination, severe hydramnios was identified with an amniotic fluid index (AFI) of 39.
No placental or fetal lesions were described
at that time. Transfer to our institution, a tertiary hospital, for further evaluation and fetal
benefit was performed. At the time of admission to our hospital, the physical examination
was unremarkable except for a fundal height
of 39 cm. No further change in the cervix was
documented at that moment. A level II obstetric
sonogram was performed which confirmed the
presence of severe hydramnios and identified a
large 5.6 x 6.5 x 5.5 cm hypoechoic lesion near
the fetal surface of an anterior implanted placenta. It contained areas of significant vascular
flow as documented by color Doppler. These
findings were consistent with a chorioangioma
(see Figures 1 & 2).
At 265/7 weeks of gestation, under sonographic guidance, an amnioreduction was
performed with removal of two liters of clear
amniotic fluid. An AFI of 24 was measured immediately after the procedure
that was well tolerated by both fetus and
mother.
Two days later, the patient developed
regular uterine contractions and was
found with a cervical exam of 8 cm dilatation, 90% effacement and bulging
membranes. She delivered vaginally
a single living baby boy at 27 weeks of
gestation, birth weight of 1,244 gm, and
Apgar scores 3, 5 and 7 at 1, 5, and 10
minutes respectively. He did not survive
the neonatal period due to complications
of prematurity.
Figures 1. Figure 1A (Left): Ultrasound image of Chorioangioma (arrows). Figure 1B
(Right): Ultrasound image of Chorioangioma shows color Doppler enhancement of
the lesion (arrow).
The placenta was delivered, and examined grossly showing a large wellcircumscribed raised mass covered by
membranes on the fetal surface at 1.5
cm from cord insertion (see Figures 3 &
4). The patient developed a post partum
hemorrhage secondary to uterine atony
that responded to oxytocin and uterine
massage.
3
Figure 2. Placenta
after
delivery with
chorioangioma
visible
as a well-circumscribed
large mass in
the fetal surface at 1.5cm
from the from
cord
insertion
(arrow).
37
37
The placenta was sent to Pathology
for histologic examination, which confirmed the presence of a chorioangioma.
The placenta was received in formalin,
weighed 390 g, and measured 19.2 x
14.5 x 4.5 cm after trimming of both cord
and membranes. Externally, it presented
a bulging mass in the fetal surface, located 1.5 cm from the cord insertion. Upon
serial sectioning through the disc, a 4.5
x 3.7 x 3.0 cm well-circumscribed single
mass was observed beneath the chorionic plate abutting the fetal surface. The
cut surface was homogeneously tan with
tiny hemorrhagic areas. On microscopy,
the mass revealed multiple capillary type
vascular channels within a loose fibrous
stroma consistent with a chorioangioma
(see Figures 5 & 6). The adjacent chorionic villi had villous stromal fibrosis.
DISCUSSION
The majority of chorioangiomas present as encapsulated intra-placental single lesions projecting towards the fetal surface usually near the cord
insertion (2). They can show various histopathologic characteristics, ranging from vascular to cellular, and can present degenerative changes (5).
Prenatal diagnosis is possible with the help of
Color Doppler and magnetic resonance (5). Sonographically, these tumors present as well circumscribed, rounded, predominantly hypoechoic
lesion near the chorionic surface and protruding
into the amniotic cavity. Color Doppler will show
increased blood flow among the ones that are
clinically significant (1).
Commonly, small lesions remain asymptomatic
and go undetected until pathologic examination
of the placenta is performed after delivery. Large
chorioangiomas (usually greater than 4-5 cm) frequently cause both maternal and fetal complications such as those described in Table 1 (2,3).
A high perinatal death rate (30-40%) is associated with these lesions mostly secondary to either excess amniotic fluid accumulation due to
leakage through the abnormal vessels causing
preterm labor (6), thrombocytopenia or severe
anemia. Fetal anemia and thrombocytopenia can
occur secondary to either sequestration of blood
or damage to erythrocytes associated with turbulent flow. Blood sequestration may also produce
fetal hypovolemia that can cause decreased somatic flow to fetal tissues and increase the risk of
growth retardation. Congestive heart failure, hydrops, and fetal death can be secondary to high
output failure and severe anemia (7). Elevations
of both maternal serum and amniotic fluid alphafetoprotein have been reported in the presence of
placental chorioangiomas (8, 9). An increase in
membrane permeability through the lesion is the
most likely cause.
Hydramnios has been reported to occur in 15
to 35% of large chorioangiomas even in the absence of other signs of fetal compromise (5).
Leakage of fluid through the chorioangioma
into the amniotic fluid could explain the high incidence of hydramnios in some of these cases. Such a condition would not be expected to
respond to treatments that reduce fetal urine
output such as Indomethacin. A greater risk of
preeclampsia has also been suggested and
can be attributed to areas of hypoxic trophoblast caused by defective vascularization (7).
Zanardini et al, found that the median gestational
age at presentation was 28 + 4 (range 23 + 2
to 35 + 1) weeks and delivery 37 + 1 (range, 31
+ 6 to 41 + 2) weeks (2). A number of treatments
have been attempted with limited success mainly directed to prolong pregnancy (2). These have
included amnioreduction, fetal blood transfusion
if anemia is present, or vessel occlusion or ablation using laser therapy in an attempt to reduce
blood flow to the tumor. Ultimately delivery may
be needed in the presence of severe fetal compromise (1,2).
This patient’s clinical presentation is characteristic of a large placental chorioangioma. She
developed complications associated to large tumors: elevated MSAFP, preterm labor, and hydramnios. Our report presents an interesting and
rare case of severe hydramnios with consequent
preterm labor and delivery in the second trimester leading to neonatal death. The first two level
II sonographic studies done at 18 and 27 weeks
failed to identify this placental lesion. An earlier
diagnosis could have led to closer monitoring
and prevention of the development of severe hydramnios with resultant preterm labor by timely
performing serial amnioreductions. Obstetricians and perinatologists should be aware of the
possible diagnosis of chorioangioma when hydramnios or fetal hydrops is present since early
diagnosis may be the key to prevention of fetal
complications and neonatal survival.
REFERENCES
1. Cunningham et al. Abnormalities of the Placenta, Umbilical Cord and Membranes. Williams Obstetrics 2010;
23: 580-581.
2. Zanardini et al. Giant Placental chorioangioma: natural
history and pregnancy outcome. Ultrasound Obstet Gynecol 2010; 35: 332–336.
3. Harigaya et al. Premature Infant With Severe Periventricular Leukomalacia Associated With a Large Placental
Chorioangioma: A Case Report. Journal of Perinatology
2002; 22, 252–254.
4. Benirschke, K. Recent trends in chorangiomas, especially those of multiple and recurrent chorangiomas.
Pediatric Developmental Pathology 1999; 2(3):264-269.
5. Amer et al. Chorangioma and related vascular lesions
of the placenta-a review. Fetal Pediatric Pathology 2010;
29(4):199-206.
6. Shalev E. Prenatal diagnosis of placental hemangioma
and clinical implication; a case report. Int J Gynecol Obstet. 1984, 22:291.
7. de la Vega A. Case Files in Obstetric Sonography.
Case 77, Placental Chorioangioma. Medical Books in
Print. P.R. 1999, p155-6.
8. Willard DA, Moeschler JB. Placental chorioangioma: a
rare cause of elevated amniotic fluid alpha feto protein. J
Ultrasound Med. 1986, 5:221.
9. Schnittger A, et al. Raised maternal serum and amniotic fluid alpha feto protein levels associated with a placental hemangioma-case report. Br J Obstet Gynaecol.
1980, 87:824.
38
Figures 3. Figure 3A (Left):
Note vascular mass (upper
area), adjacent to a group
of fibrotic villi (below). H &
E, 10 X. Figure 3B (Right):
At higher magnification,
numerous vascular capillary-type vessels are seen
within a loose fibrous stroma. H & E, 20X.
RESUMEN
Table 1. Complications associated with large placental
chorioangiomas.
39
Los corioangiomas placentarios son tumores de
la placenta relativamente
comunes que ocurren en
aproximadamente un 1%
de las placentas estudiadas histológicamente.
Estos tumores solo dan
manifestaciones clínicas
en embarazos raros a una
edad gestacional media
de 28 semanas. Nuestro
artículo presenta un caso
interesante y muy raro de
un caso de hidramnios
severo que tiene como
consecuencia un parto
prematuro en el segundo
trimestre que culminó en
una muerte neonatal. Un
diagnóstico más temprano
de la condición pudo haber
llevado a un monitoreo
más cercano y por lo tanto
prevenir el desarrollo de hidramnios severo llevando
a parto prematuro.
40
Laparoscopic
management of an
adnexal torsion with
transabdominal
oophoropexy
performed in a first
trimester pregnant
woman: A case report
Omar Pérez-Rodriguez MDa*, Alexandra OrtizOramas MDa, Brayan Stuart- Vazquez MDa
Departments of Obstetrics and Gynecology; St. Luke’s
Episcopal Hospital, Ponce, Puerto Rico.
*Corresponding author: Omar Perez Rodriguez MD Condominio Estancias del Oriol, 1010 calle Julia de
Burgos Apto. 410, Ponce, Puerto Rico 00728. E-mail:
[email protected]
a
INTRODUCTION
Ovarian torsion during pregnancy is a rare
event that can be managed conservatively
though the risk of recurrence increase using
this approach. Laparoscopic oophoropexy using different techniques has been recommended to increase adnexal salvage and prevent recurrence. An innovative technique performing
a laparoscopic transabdominal oophoropexy
was done in a first trimester pregnancy and it
showed to be a surgically feasible procedure
preventing ovarian torsion recurrence with no
obstetrical complications.
Case History
A 27-year-old primigravid female patient with
an intrauterine pregnancy of 11 5/7 weeks of
gestation is hospitalized due to acute onset
abdominal pain at the right lower quadrant of
one day of evolution. The physical examination
was suggestive of acute appendicitis but abdominopelvic sonogram findings were not conclusive. The transvaginal ultrasound revealed
an intrauterine pregnancy of 12 weeks of gestation, a non-specific small amount of free fluid
in the right adnexa, and a normal gray-scale
and color Doppler study of the adnexa. An exploratory laparoscopy was performed, which
showed a right non-cystic adnexal torsion,
which immediately recurred after uncoiled
ABSTRACT
This is a case of a unilateral ovarian torsion
in a 27-year-old female with 11 5/7 weeks of
gestation who underwent laparoscopic detorsion and transabdominally oophoropexy
using an innovative surgical technique.
The patient continued with her prenatal
care and vaginal delivery at term without
complications.
Index words: laparoscopic, management,
adnexal, torsion, transabdominal, oophoropexy
(see Figure 1). A transabdominal oophoropexy was performed using a straight needle
Prolene 3-0 suture. The suture was inserted
transabdominally from the external abdomen
into the abdominal cavity, through the ovary in
its uncoiled position, and then back out the
abdominal cavity proximal to the insertion site.
The ovary was then fixated transabdominally
to the right anterolateral abdomino-pelvic wall
(see Figure 2). The oophoropexy suture was
removed three days later in the follow-up office
visit. The patient continued with her prenatal
care without further complications. She was
admitted to antepartum ward at 38 5/7 weeks
of gestation in the active phase of labor and
had a vaginal delivery without complications.
DISCUSSION
Adnexal torsion has a general prevalence of
2.7% (1). Approximately one in 1800 pregnancies are complicated by adnexal torsion, most
commonly between six and 14 weeks of gestation, and these compose 20 to 25 % of all torsion
cases (2). As conservative management has
evolved, the incidence of repeated torsion will
likely increase as well. The risk of recurrence
is increased when torsion involves a non-cystic
adnexa (3). Laparoscopy is well suited for the
diagnosis and treatment of adnexal torsion occurring during the first trimester of pregnancy
(4). Laparoscopic oophoropexy is recommended in emergency situations to increase
adnexal salvage and to prevent a recurrence
(5). In a reported case series of eight woman
who underwent oophoropexy via different approaches, one patient had a recurrence after
oophoropexy and it was attributed to the surgical technique; fixation to the abdominal wall
using an absorbable suture (6). The case presented here shows non-recurrence of adnexal
torsion in a pregnancy delivered at term without
further complications, after trans-abdominal
oophoropexy, with the use
of non-absorbable suture.
Attention should be given
to this innovative technique
because it is surgically feasible, providing access to
the adnexal structures for
transabdominal oophoropexy. In addition, the suture
can easily be removed due
to the trans-abdominal approach. Furthermore, the
procedure prevented an
ovarian torsion recurrence,
which could necessitate further interventions, such as
laparotomy.
REFERENCES
1. Sunita Tandulwadkar, Amit
Shah, Bhavana Agarwal. Detorsion and conservative therapy for
twisted adnexa: Our experience.
Journal of gynecological endoscopy and surgery 2009; 1(1):21-26.
2. Courtney A. Woodfield, Elizabeth Lazarus, Karen C. Chen, William W. Mayo-Smith. Abdominal
Pain in Pregnancy: Diagnoses
and Imaging Unique to Pregnancy—Review. American Journal of
Roentgeneology June 2010; 194:
14-30.
3. Pansky M.,Smorgick N., Herman A., Schneider D, Halperin
R. Torsion of normal adnexa in
postmenarchal woman and risk
of recurrence. Obstet Gynecol.
2007;109:355-359.
4. Morice P, Louis-Sylvestre C,
Chapron C, Dubuisson JB. Laparoscopy for adnexal torsion in
pregnant women. J Reprod Med.
1997; 42: 435-439.
5. Djavadian D, Braendle W, Jaenicke F. Laparoscopic oophoropexy for the treatment of recurrent
torsion of the adnexa in pregnancy: case report and review.
Fertil Steril. 2004 ;82(4):933-6.
Fuchs N., Smorgick N., Tovbin Y.,
et al. Oophoropexy to prevent adnexal torsion:how, when, and for
whom? J minim Invasive Gynecol.
2010;17:205-208.
Figure 1. Image of the torsioned adnexa.
Figure 2. Image of transabdominal oophoropex
RESUMEN
Este es el caso de una torsión ovárica unilateral, en una paciente de 27 años con un
embarazo intrauterino de 11 5/7 semanas de gestación, el cual fue laparoscópicamente
destorcido y fijado a través del abdomen usando una técnica quirúrgica novedosa. Luego
del procedimiento la paciente continuo con su cuidado prenatal y tuvo un parto vaginal a
termino sin complicaciones.
41
42
Chylous jejunal cyst
causing volvulus in a
child:
Case report and
literature review
Liliana Guzmán MDa, Eittel Oppenheimer MDb,
Humberto Lugo-Vicente MDc*, Maria Correa MDd
Department of Pediatrics and Residency Program, San
Juan City Hospital, San Juan, Puerto Rico.
Department of Surgery, UPR School of Medicine.
c
Section of Pediatric Surgery, Department of Surgery,
UPR School of Medicine.
d
Department of Pathology, UPR School of Medicine.
*Corresponding author: Humberto Lugo-Vicente MD
– PO Box 10426, Caparra Heights Station, San Juan,
Puerto Rico 00922. E-mail: [email protected]
Poster presentation at the 60th Annual Puerto Rico Pediatric Society Congress, February 15, 2013, Sheraton
Puerto Rico Convention Center Hotel, San Juan, Puerto
Rico.
a
b
ABSTRACT
Chylous jejunal cysts are extremely rare
entities and if not diagnosed promptly may
lead to severe complications like bowel
obstruction, loss of small bowel and even
death. We present the case of a 4 year-oldmale referred to our institution with severe
abdominal pain, constipation, abdominal distention and radiological findings of
large amount of fluid in the lower abdomen
with associated bowel obstruction. Operative findings were that of large chylous jejunal cyst causing segmental volvulus. Resection of the involved jejunal segment and
cyst along with bowel detorsion was undertaken. Literature review on the subject follows.
Index words: chylous, jejunal, cyst, volvulus, child, case, report
INTRODUCTION
Chylous mesenteric cysts are rare intraabdominal lesions mostly found in children. Their
lack of specific or pathognomonic signs makes
them difficult to diagnose early (1). Although
often asymptomatic, they can sometimes
reach such size and volume as to cause pain,
bowel obstruction and other specific symptoms
(2). Clinical presentation of chylous mesenteric cysts varies and may be misleading due
to unawareness of the condition. Occasionally, the diagnosis is made during surgery performed for unrelated reasons. If not promptly
diagnosed and managed these lymphatic
malformations can lead to severe complications including death. A case of volvulus and
small bowel obstruction due to a large chylous
mesenteric jejunal cyst in a child is presented.
Literature review on the subject follows.
Case History
A 4 year-old-male with past medical history of
chronic gastritis and eosinophilic esophagitis
was in his usual state of health until December
6, 2012 when he began with the acute onset
of abdominal periumbilical pain and toward
the left side of the abdomen, constant, nonradiating, associated with three episodes of
projectile vomiting of gastric contents, obstipation and poor oral intake. Mother denied fever,
diarrhea or any other associated symptom.
Patient was taken to ER at Saint Luke’s Hospital where pain increased in intensity. An abdominal CT-Scan was performed with radiological findings suggestive of a large amount
of fluid in the lower abdomen, likely loculated
that may represent ascites; however the possibility of a cystic mass such as lymphocele was
also entertained. There was associated small
bowel obstruction (see Figure 1). Patient was
transferred to our institution for pediatric surgical evaluation.
Upon arrival to the University Pediatric Hospital patient physical examination demonstrated
blood pressure of 101/53, pulse 105, respiratory rate 24, temperature 37°C and oxygen
saturation 99%. The child was alert, active
and oriented with nasogastric tube in place
draining bilious content. The abdominal exam
revealed bowel sounds present, distended
abdomen, periumbilical and epigastric tenderness to palpation and no hepatosplenomegaly.
Laboratory workup can be appreciate in Table
1. A simple abdominal film was performed (see
Figure 2). It revealed air distended, elongated
small bowel in the left upper quadrant with distal air. Findings were worrisome for an obstructive process/inflammatory process.
Patient was taken for surgery. Under general anesthesia using a midline incision a large chylous
Figure 1: Abdominal CT-Scan with a large loculated ascites or cyst.
Table 1: Laboratory and Diagnostic workup.
43
cyst of jejunum measuring 20 x 16 x 4 cm
was delivered from
the abdominal cavity
associated with volvulus of the involved
segment of bowel
(see Figure 3). The
chylous cyst along
with the involved section of proximal jejunum was resected
and a side-to-side
mechanical
anastomosis performed.
Following resection
it was possible to derotate the volvulus
270-degree counterclockwise helping a
segment of distal ileum recover viability.
Since Treitz was in its
normal anatomic position the cecum was
returned to the right
lower quadrant and
an incidental appendectomy performed.
The child tolerated
feedings 48 hours after surgery and was
later discharged from
the hospital in his 5th
postoperative
day.
The chylous nature
of the cyst was confirmed on histopathology.
Pathology
Gross
examination
of the mass revealed
a cyst adhered to
a segment of small
bowel (See Figure 4).
The cyst measured
20 x 16 x 4 cm and
weighed 1,100 g. The
external surface was
tan and smooth with
vasculature pattern.
On opening, it contained light tan milky
fluid. The internal lining was smooth and
glistening and the wall
Figure 2: KUB with air distended, elongated small
bowel loops are visualized
in the left upper quadrant
with distal air.
44
Figure 3: Large jejunal chylous cyst causing segmental volvulus of the involved segment
of bowel.
Figure 4: Gross examination of the mass revealed a
cyst adhered to a segment
of small bowel. The cyst
measured 20 x 16 x 4 cm
and weighed 1,100
45
measured up to 0.1 cm in thickness. It had no
communication with the bowel lumen. The 8
cm segment of small bowel presented a patent
lumen and an unremarkable mucosa. Sections
of the cyst revealed a single layered cuboidal
epithelium lining (See Figure 5).
Figure 5: Cyst adjacent to bowel wall, seen
at right side of image. The cyst is lined by
a single layer of low cuboidal to flat epithelium (H & E 10x).
Patients with mesenteric lymphatic malformations may present with non-specific signs and
symptoms like an asymptomatic mass discovered incidentally. Alternatively, the presentation
may consist of abdominal pain, an increase in
abdominal girth, nausea, vomiting, anorexia,
diarrhea or constipation (5). The small bowel
mesentery is a common site of origin for mesenteric cysts, some of which contain chylous
fluid (6).
Chylous mesenteric cysts can gradually enlarge
DISCUSSION
Mesenteric lymphatic malformations are rare
intraabdominal tumors that usually present in
childhood and are more commonly seen in
males (3). Lymphatic malformations are uncommon abdominal masses thought to represent congenital disorders of the lymphatic
system. They are thought to arise from the
embryonic retroperitoneal lymph sac (4). Collection of chyle in this portion of the lymphatic
system may lead to cyst formation creating an
abdominal mass effect. The precise cause is
still not clear. Therefore presentation and diagnosis may be difficult.
46
and start to compress the intestines when
they have no more room to grow. If not treated promptly they can even rupture and cause
chylous ascites. It is difficult to explain these
phenomena as few reports provide details. In
our case the large cyst was filling the abdominal cavity and mimicked loculated ascites on
abdominal CT scan. Abdominal ultrasound
and CT scan are considered to be quite diagnostic of this condition (7). In very rare occasion mesenteric chylous cyst can cause bowel
obstruction from direct impinging in the bowel
wall or torsion like in this case. The patient
may be at risk of bowel strangulation, necrosis, infection and even death.
Review of literature shows scarcity of cases
of chylous mesenteric cyst causing volvulus
in a child. While volvulus is an uncommon
complication, it should be considered in any
child with sonographic findings of an abdominal lymphatic malformation who present with
acute abdominal pain (5). The definitive treatment for chylous mesenteric cyst is complete
surgical excision. Complete excision of cyst
with or without bowel resection is the procedure of choice in various reported cases (8).
During surgery it is often necessary to perform
a bowel resection because of the close relation
between the cyst and the intestinal wall.
In summary, chylous mesenteric cysts are rare
entities that should be included in the differential diagnosis in a child with acute abdominal
pain, vomiting and abdominal distention. The
clinical presentation may be associated with its
location. Although rare they can cause severe
life threatening complications. Good prognosis
follows with surgical excision and early diagnosis.
RESUMEN
Los quistes mesentéricos de yeyuno son
entidades extremadamente raras y si no
son diagnosticadas rápidamente, pueden
llevar a complicaciones severas como obstrucción intestinal, perdida de intestino y
hasta muerte. Presentamos el caso de un
varón de 4 años de edad referido a nuestra institución con dolor abdominal severo,
distención, constipación y hallazgos radiológicos de gran cantidad de fluido en
abdomen inferior además de obstrucción
intestinal
distal.
Hallazgos operatorios consistieron de un enorme
quiste de contenido quiloso en el
yeyuno causando
vólvulo del intestino.
Resección
del segmento afectado y corrección de la torsión
fue curativa para el
paciente. Repasamos la literatura
actualizada de esta
condición.
REFERENCES
(1) Chen HP, Liu WY, Tang YM, Ma BY, Xu B, Yang
G, Wang XJ (March 1, 2011) Chylous mesenteric
cysts in children. Surgery Today.Volume 41,Issue 3,
pp 358-362.
(2) Domenico Tebala, G MD, Camperchioli, I MD,
Tognoni, V MD, Noia,M MD, Lucio Gaspari, A MD.
(July-September 2010) Laparoscopic Treatment
of a Huge Mesenteric Chylous Cyst. Journal of the
Society of Laparoendoscopic Surgeons, Volume
14, Number 3. pp. 436-438(3)
(3) Daniel J. Kirzeder and J. Herman Kan.(August
2007) Mesenteric lymphatic malformation. Pediatric
Radiology. Volume 37, Issue 8, p 845. [Available online] http://link.springer.com/article/10.1007/s00247007-0521-2/fulltext.html
(4) Chung JH, Suh YL, Park IA, et al (1999) A pathologic study of abdominal lymphatic malformations.
Journal of Korean Medical Science. 14:257–262
(5) Traubici,J, Daneman,A,Wales, P, Gibbs,D,
Fecteau,A, Kim,P. (2002) Mesenteric lymphatic malformation associated with small-bowel volvulus: two
cases and a review of the literature. Pediatric Radiology. 32: 362–365 DOI 10.1007/s00247-002-0658-y
(6) Haney PJ, Whitley NO. (June 1,1984) CT of benign cystic abdominal masses in children. American
Journal of Roentgenology.Volume 142, no. 6 12791281.
(7) Fujita N, Noda Y, Kobayashi G, Kimura K, Watanabe H, Masu K, Nagano M, Mochizuki F, Yusa S,
Yamazaki T. Chylous cyst of the mesentery: US and
CT diagnosis. Abdominal Imaging. 1995;20(3):259–
261. doi: 10.1007/BF00200410. [PubMed] [Cross
Ref]
(8) Prakash A, Agrawal A, Gupta RK, Sanghvi B,
Parelkar S. Early management of mesenteric cyst
prevents catastrophes: A single centre analysis of
17 cases. Afr J Paediatric Surgery [serial online]
2010;7:140-3.Available from: http://www.afrjpaedsurg.org/text.asp?2010/7/3/140/7041
47
48
An unusual
presentation of
Herpes Simplex
in an immunocompromised
patient
Francisco Fernández González MDa*, José Betancourt MDa, Juan C. Malpica MDa, Iván Laboy
MDa, Miguel Colón MDb
Department of Internal Medicine, San Juan City Hospital.
b
Department of Infectious Diseases, San Juan City Hospital and Hospital Auxilio Mutuo.
*Corresponding author: Francisco Fernández-González
MD - Internal Medicine Department, San Juan City Hospital, CMMS #79 P.O. BOX 70344, San Juan, Puerto
Rico 00936-8344. E-mail: [email protected].
a
INTRODUCTION
Herpes simplex virus (HSV) belongs to
the herpesviridae family. It is responsible for
multiple common conditions such as oral and
genital lesions, encephalitis, Bell’s palsy, and
herpes ophtalmicus (1). Once it is diagnosed,
the clinician should be aware of any immunosuppressive disorder, which is common when
HSV is present. Rarely, a disseminated presentation of HSV can present, which is more
common on immunosuppressed patients. It is
unusual and could be a challenge for recognition. We present a case of disseminated HSV
with emphasis on the clinical presentation,
biochemical findings, and dermopathologic
description.
Case History
A 73 years-old-male with history of non-Hodgkin lymphoma and of chemotherapy 10 years
ago arrived to the emergency room complaining of a one week evolution with diffuse vesicular painful rash throughout his body, associated with constitutional symptoms including
fever, chills, malaise, and generalized weakness. In addition, he referred non-bloody watery diarrhea without abdominal pain. He was
recently discharged home from a previous
admission two weeks before due to a pneumonic process. Upon physical examination he
was found oriented in 3 spheres. Vital signs
revealed a pulse 93 per minutes, arterial blood
pressure 130/86 mmHg, respiratory rate at 20
per minutes, and an adequate temperature of
ABSTRACT
Herpes simplex virus (HSV) is a hostadapted human pathogen. HSV-I usually
infects non-genital sites at a variety of
locations. HSV-2 primarily involves genitalia. Both types can cause genital and
orofacial infections, which are clinically
indistinguishable. Initial HSV infection
is usually asymptomatic or mild and
self-limited, but instead of disappearing
from the body during convalescence,
the virus establishes a latent infection
that persists for life. Rarely, there is severe visceral dissemination. This is a
case report of an unusual presentation
of herpes simplex in an immunocompromised adult patient with generalized
skin lesions on the entire body. To our
knowledge, this is the first case reported in the literature of a disseminated
herpes simplex in a patient with history
of non-Hodgkin Lymphoma. Generalized HSV infection in immunodeficient
adult patients could be fatal in spite of
antiviral therapy. Early recognition of
this entity is essential to expedite appropriate treatment and avoid future
complications.
Index words: herpes, simplex, immunocompromised, patient
36.6 Celsius. He exhibited dry oral mucosa
and painless bilateral cervical lymphadenopathy. The heart examination revealed a regular
rate without murmurs and the lungs had mild
bibasilar rales. No organomegaly palpated.
The skin showed multiple vesicles on an erythematous base, without suppuration, tender,
in the abdomen, thorax, abdomen, extremities,
earlobes, and genitals (see Figures 1 and 2).
No ulcerations or urethral secretions identified
on genital area.
Significant laboratory results showed a negative varicella-zoster antibody of less than 0.91
AU (0-0.9). Herpes simplex 1/2 immunoglobulin’s IGG was remarkably high with 29 index (00.8). While Herpes simplex immunoglobulin’s
IGM was low in less than 0.91 ratio (0-0.9).
The complete blood count showed normocyticnormochromic anemia with hemoglobin level
at 10 g/dl, mean corpuscular hemoglobin at
90.7, white blood cells slightly decreased at 3.9
103/µl (4.8-10.8 103/µl). No electrolyte disturbances identified on blood chemistry. A punch
biopsy of skin lesions showed intra-epidermal
vesicles with ballooning consistent with herpes
virus (see Figure 3).
Figure 2: Vesicles on erythematous base
seen on ears.
The patient was hospitalized due to volume depletion, acute gastroenteritis and disseminated herpes simplex virus. The volume
depletion resolved with copious intravenous
fluids with normal saline solution. The viral infection was treated with intravenous acyclovir
10mg per kilogram every 8 hours for ten days,
which completely resolved the skin vesicles.
The patient was also evaluated by hematology
and oncology services due to relapse of nonHodgkin lymphoma. Patient was discharged
home with follow up on clinics of hematology
and oncology.
Figure 1: Disseminated cuteanous herpes
on thorax and abdomen.
DISCUSSION
Figure 3: Punch biopsy of skin lesion
showed an intra-epidermal vesicle with ballooning, consistent with herpes virus.
Disseminated cutaneous herpes simplex is
rare, but it may occur in immunocompromised
patients, including those with hematological malignancies and following bone and organ transplants (2). It is caused by either HSV-1, which
usually affects oral area, or HSV-2, being more
frequent on genital area. This virus is typically
transmitted from direct contact with the lesion
or body fluid of an infected person with HSV.
The remarkable capacity of the HSV to persist
for life in its natural host, as well as its longterm persistence in human population, depends on its capacity to establish and maintain
latent infection and periodically reactivates.
The clinical manifestations are determined by
the prior experience of the host with HSV, and
host factor such as age, nutrition status and
immunocompetence (3). Disseminated forms
49
can affect skin as well as multiple target organs
such as brain, liver, adrenal glands, and eyes.
Skin lesions are present as eruption of vesicles,
pustules or erosions. It is usually accompanied
with constitutional symptoms such as fever and
lymphadenopathy. The condition may resolve
spontaneously but sometimes it could worsen
progressively. The mortality rate is high if disseminated, especially in neonates, which reach
85% if untreated (4)
Acknowledgments
We are grateful to our residency programattending physicians in internal medicine at
San Juan City Hospital for their daily efforts in
strengthening our education.
The present case showed a patient with a relapse of non-Hodgkin lymphoma who had disseminated cutaneous lesions caused by HSV.
He had elevated herpes simplex 1/2 immunoglobulin’s IGG with a skin biopsy revealing an
intra-epidermal vesicle with ballooning, which
is consistent with HSV. Herpes zoster infection
was ruled out due to negative serum antibodies. Patient’s skin lesions appeared scattered,
rather than following a dermatomal distribution
as seen on Herpes zoster. Although vesicle’s
fluid for polymerase chain reaction (PCR) was
not available for distinguishing whether HSV 1
or 2 caused it, there was clear evidence that
HSV was the etiologic pathogen. Viral cultures
were neither performed. Fortunately, he didn’t
present dissemination to other organs.
Prompt treatment with intravenous acyclovir on
disseminated HSV is imperative to avoid serious complications and is associated with improved outcomes (5). Our patient responded
well with intravenous acyclovir, resolving all
cutaneous lesions. Antivirals such as acyclovir
reduce the viral shedding and hence could decrease symptom duration.
In conclusion, this case serves us to be alert
for early management in any cutaneous lesion
that could be an atypical presentation of an infectious process in an immunocompromised
patient.
REFERENCES
1. Xu F, Sternberg MR, Kottiri BJ et al.: Trends in herpes
simplex virus type 1 and type 2 seroprevalence in the
United States; JAMA 2006, 296(8): 964-73.
2. Justice E, Khan S, Logan S et al.: Disseminated cutaneous herpes simplex virus-1 in a woman with rheumatoid arthritis receiving Infliximab: A case report; Journal of
Medical Case Reports, 2008, 2: 282.
3. Herget GW, Riede UN, Schmitt-Gräff A et.al: Generalized herpes simplex virus infection in an immunocompromised patient-report of a case and review of the literature.
Pathology-Research and Practice, 2005: 201, 123-29.
4. Kimberlin D: Herpes simplex virus, meningitis and encephalitis in neonates. Herpes. 2004; 11:65A-76A.
5. Czartoski T, Liu C, Koelle D et al: Fulminant, acyclovirresistant, herpes simplex virus type 2 hepatitis in an immunocompetent woman; Journal of Clinical Microbiology,
2006, 44, (4): 1584-86.
50
RESUMEN
El virus del herpes simple es un
patógeno que se adapta al ser humano como huésped. El virus del herpes simple tipo 1 usualmente afecta
aéreas no genitales así como diferentes partes del cuerpo. El tipo 2 afecta
principalmente los genitales. Ambos
tipos pueden causar infecciones en
la región genital y orofacial, los cuales son clínicamente indistinguibles.
Usualmente la infección por el virus
del herpes simple es asintomática,
leve y resuelve por si misma, sin embargo en vez de desaparecer del cuerpo durante el periodo de convalecencia el virus se mantiene latente y
persiste toda la vida. Rara vez hay diseminación visceral. Este es un caso de
una presentación inusual del herpes
simple en un paciente inmunocomprometido, con lesiones diseminada
por todo el cuerpo. Hasta el momento
este es el primer caso reportado en la
literatura de herpes simple diseminado en un paciente con historial médico de linfoma no-Hodgkin. Infección
de herpes simple diseminado usualmente es fatal en el paciente adulto
inmunodeficiente a pesar de la terapia
antiviral existente. El reconocimiento
temprano de esta entidad es esencial
para poder dar un tratamiento apropiado y evitar futuras complicaciones.
51
ABSTRACT
Endometriosis is defined as the presence of endometrial tissue in extra uterine sites. It affects 5-15% of females during their reproductive years. Thoracic
endometriosis syndrome is characterized by the presence of functional endometrial tissue within the pleura, the lung
parenchyma or the airway. The overall
prevalence of this condition is unknown
due to a lack of epidemiological studies,
variety of symptoms, signs and locations. We present the first reported case
of recurrent catamenial pneumothorax
in Puerto Rico and a review of recent literature.
Index words: thoracic, endometriosis,
Puerto Rico
Thoracic
Endometriosis:
first reported case in
Puerto Rico and
review of literature
Carlos García Gubern MDa*, Lissandra Colon Rolón MDa, Orlando Vazquez Torres MDb,
Gretchen Martinez Alayón MDb, Alexis Santos
Santiago MDa, Eugenio Mulero Portela MDc
Department of Emergency Medicine, Hospital San Lucas Ponce, Ponce School of Medicine and Health Sciences.
b
Department of Internal Medicine, Hospital San Lucas and Ponce School of Medicine and Health Sciences.
c
Section of Cardiothoracic Surgery, Department of Surgery, Hospital San Lucas Ponce and Ponce School of
Medicine and Health Sciences.
*Carlos Garcia Gubern MD – PO Box 195504, San Juan
Puerto Rico 00919. E-mail: [email protected]
a
INTRODUCTION
Endometriosis is defined as the presence of
endometrial tissue in extra uterine sites like
ovaries, uterosacral ligaments, cul-de-sac and
peritoneum. It affects 5-15% of females during
their reproductive years (1). Other reported extra uterine sites are the uterine tubes, uterus
serosal surface, sigmoid colon, small intestine
and rectovaginal septum. Ectopic endometrium is referred when endometriosis is found
in extra pelvic organs like the umbilicus, in abdominal scars, in the breast, the extremities,
the pleural cavity and the lung (2, 3).
Extra pelvic endometriosis has many histologic patterns; they vary from typical endometrial
glands to an abundance of fibrous tissue (4).
The prevalence of this rare condition is unknown due to a lack of epidemiological studies
based on the fact that a wide variety of symptoms, signs and locations made even harder
to establish this already difficult diagnosis (3,
4, 5,).
The location of extra pelvic endometriosis is
defined by anatomical regions: urinary tract
endometriosis, bowel-omental endometriosis,
pulmonary endometriosis and endometriosis
of other sites.
Thoracic endometriosis syndrome (TES) is a
rare and uncommon disorder characterized by
the presence of functioning endometrial tissue
within the pleura, the lung parenchyma or the
airways with an incidence less than 1% (6).
Catamenial pneumothorax (CPT) is the most
frequent presentation of thoracic endometriosis syndrome (2, 3, 6, 7). Other reported
clinical presentations are: catamenial hemothorax (14%), catamenial hemoptysis (7%),
and endometriotic lung nodules (6%). The
most common presenting symptoms of TES
are chest pain (90%) and dyspnea (31%) (6).
The term Catamenial is derived from a Greek
word meaning monthly; it was first described
by Maurer and colleagues’ in 1958 (2, 3, 6, 7).
Since then, 229 cases of this unique entity of
spontaneous recurring pneumothorax have
been reported (2). We present the first reported case of recurrent catamenial pneumothorax
in Puerto Rico and review current literature of
thoracic endometriosis.
Case History
A 40 years-old-female G4P3A1 with past
medical history of bronchial asthma, cardiac
arrhythmias, pelvic endometriosis, systemic
lupus erythematosus and recurrent spontaneous pneumothorax, present to our institution
complaining of non radiating aching chest pain
in the right side with intensity 10/10, associated to shortness of breath, dry cough (traces of
blood) and pink colored nasal secretions, since
2-3 weeks prior to our evaluation. Patient denied palpitations, diaphoresis, dizziness, fever
or chills. Two years prior to evaluation patient
had an episode of right-sided pneumothorax;
that was treated with chest tube and elicited a
negative workup for pulmonary embolism.
Patient referred both episodes occurred about
24-36 hours after the onset of menses. She
reported several unsuccessful treatments for
her endometriosis too. Upon examination, patient was found pale, with dry cough and short
of breath complaining of chest pain. Chest Xray demonstrated a right-sided pneumothorax
that resolved with a tube thoracostomy. Patient was then admitted and consulted with the
cardiothoracic surgery service for a video assisted thoracoscopy (VAT)
During VAT, multiple diaphragmatic perforations (0.2-0.5 cm) in the tendinous part were
visualized and an open thoracotomy was performed. Diaphragmatic perforations were sutured and biopsy was taken for histopathologic
report. Histologic examination revealed chronic pleuritis with marked pleural thickening and
focal changes consistent with pleural endometriosis. She was consulted to OB/GYN service
and treated with leuprolide. Nine months after
discharge patient has been free symptoms.
DISCUSSION
The diagnosis of TES is challenging, and it is
often delayed until the recurrence of symptoms
establishes its relationship with menses, therefore, made on the basis of the clinical history
virtually a diagnosis of exclusion. (8-12). Neither CT nor endoscopy is diagnostic specific
for TES, the crucial issue for establishing the
diagnosis is the recurrence of the symptoms
which occur along the menstrual cycle (3). A
definitive diagnosis is achieved by histopathologic confirmation of biopsy (3, 6-8).
Patients are of reproductive age, often nulliparous with long standing symptoms that occur
along with the menstrual cycle. The symptoms
usually present within 24 to 72 hours of the beginning of menstruation. The mean age is 34.2
+ 6.9 years (15-47 years), with age 36.1 + 6.4
years at time of intervention (7, 10, 13, and 14).
The pathogenesis of TES remains uncertain
but three different theories have been proposed (9, 10):
1. Migration of air through the uterus and fallopian tubes into the abdomen and through
diaphragmatic fenestrations into the thorax.
This theory is supported by the fact that plication of diaphragmatic perforations and tubal
ligation have cured CPT (7).
2. Endometrial tissue microembolization.
3. High levels of serum prostaglandins in the
perimenstrual period might sensitize pulmonary blebs and make them more prone to
rupture thus causing vasospasm and bronchospasm, resulting in pneumothorax and alveolar rupture.
Medical approaches focus on the suppression of endometrial tissue by blocking the action of estrogen (15). Hormonal medication
with contraceptive drugs, GnRH analogue,
danazol and progesterone is the first choice
of treatment for CPT (5,7,15). However, hormonotherapy is found to require long-term
administration; side effects, liver injury, genital bleeding and reproduction are severely
impaired during this treatment (8,9). Hysterectomy with bilateral salpingoophorectomy
remains the definitive treatment for TES (6),
but it may be ineffective for patients receiving
estrogen replacement therapy, which may reactivate thoracic endometrial tissue (17).
CONCLUSIONS
There has been reported a diverse and a great
variety of complaints and symptoms associated with thoracic endometriosis. It is known
that it is usually related to the physiologic
function of the ectopic endometrium. The diagnosis of thoracic endometriosis should be
suspected in any woman of reproductive age
who present or has a history of spontaneous
recurrent pneumothorax or hymoptysis. It is
worth mentioning that to establish this diagnosis; the patient does not require pelvic endometriosis symptoms simultaneously. The
clinical symptoms of thoracic endometriosis
establish the diagnosis; the fundamentals of
treatment are two: surgical and medical.
The medical options consist of GN-RH Analogues. When medical options fails several
surgical procedures are described. Bilateral
ophrorectomy should be considered if multifocal pulmonary involvement is present.
52
REFERENCES
1. Gaudice LC, Kao LC: Endometriosis. Lancet 2004;
364: 1789-1799
2. Rock JA, Markham SM: Extra pelvic endometriosis: in Wilson EA (Ed): Endometriosis, New York, Alan
Liss, 1987, pp 185-206.
3. Thoracic Endometriosis Syndrome Areti Augoulea,
Irene Lambrinoudaki, George Christodoulakos, Respiration 2008; 75: 113-119.
4. D’Hooghe T. Debrock S, Meuleman C, and Hill
J, Mwenda J: Future directions in endometriosis research. Obstetric Gynecol Clin North Am 2003, 30:
221-244.
5. Joseph J. Sahn SA: Thoracic endometriosis syndrome: new observations from an analysis of 110
cases. Am J. Med 1996; 100: 164-170
6. Ziedalski, T.M., Sankaranarayanan, V., Chitkara,
R.K. Thoracic Endometriosis: A case report and literature review. J. Thoracic Cardiovascular Surg 2004;
127: 1513-1514.
7. Korom, S., Canyurt, H. Missbach, A. Schneiter, D.,
Kurrer, M.O. Haller, U., Keller, P.J. Furrer, M., Weder
W. Catamenial pneumothorax revisited: Clinical approach and systematic review of the literature J. Thorac Cardiovascular Surg 2004: 128: 502-508
8. Martinez, S., Marmol, E.E. Serra, J. Value of Thoracoscopy in the Diagnosis and Treatment of Complicated Thoracic Endometriosis in 2 patients. Arch
Bronconeumol. 2008: 44 (4): 224-5.
9. Tzunezuka, Y., Sato, H. Kodama, I., Shimizu, H.,
Kuramaya, H. Expression of CA125 in Thoracic Endometriosis in a Patient with Catamenial Pneumothorax.
Respiration 1999; 66: 470-472.
10. Chung SY, Kim SJ, Kim TH, Ryu WG, Park SJ,
Lee DY, Paik HC, Kim HJ, Cho SH, Kim JK, Park KJ,
Ryu YH: Computed tomography findings of pathologically confirmed pulmonary paenchymal endometriosis
J. Commput Assist Tomogr 2005; 29; 815-818.
11. Puma F, Carloni A, Casucci G, Puligheddu C, Urbani M, Porcaro G: Successful endoscopic Nd-YAG
laser treatment of endobronchial endometriosis, Chest
2003; 124: 1168-1170.
12.
Inoue T, Kurokawa Y, Kaiwa Y, Abo M,
Takayama T, Ansai M, Satomi S: Video assisted thoracoscopic surgery for catamenial hymoptysis, Chest
2001; 120: 655-658
13.
Wood DJ, Krishnan K, Stocks P, Morgan E,
Ward MJ: Catamenial hymoptysis: a rare cause. Thorax 1993; 48: 1048-1049
14.
Espaulella J, Armengol J, Bella F, Lain JM,
Calaf J: Pulmonary endometriosis: conservative treatment with GnRH agonists. Obstetric Gynecol 1991;
78: 535-537.
15.
Madanes AE, Farber M: Danazol, Ann Intern
Med 1982; 96: 625-630.
16. Cassina PC, Hauser M, Kael G, Imthurn B, Schroder S, Weder W: Catamenial hymoptysis: diagnosis with MRI. Chest 1997; 111: 1447 – 1450.
17.
Korom S, Canyurt H. Missbach A, Schneider
D, Kurrer MO, Haller U, Keller P, Furrer M, Weder W:
Catamenial pneumothorax revisited: clinical approach
and systematic review of the literature. J Thorac Cardiovas Surg 2004; 128: 502-508.
53
RESUMEN
Endometriosis se define como la presencia de tejido del endometrio en
lugares extrauterinos. Esta condición
afecta 5 a 15% de la población femenina en edad reproductiva. El síndrome
de endometriosis torácica es caracterizado y se define por la presencia
de tejido funcional del endometrio en
la pleura, parénquima pulmonar y la
vía aérea. Actualmente se desconoce
la prevalencia de esta condición debido a la falta de estudios y reportes
epidemiológicos, a la gran variedad de
signos, síntomas y localización. Presentamos el primer caso reportado en
Puerto Rico con diagnostico de neumotórax catamenial recurrente junto a
un repaso de la literatura actual sobre
esta condición.
La Asociación Médica vuelve
al Dorado, a la búsqueda de la
excelencia en Educación Médica,
en pautas de investigación
científica, en desarrollo de
líderes para el futuro.
Acérquese y únase a nuestro
esfuerzo por el bienestar de la
salud y del Pueblo de
Puerto Rico
54
Agenesia congénita de
huesos craneales
asociada a
hidrocefalia:
Reporte de caso
Luis Rafael Moscote-Salazara*, Sandra Milena
Castellar-Leonesb, Gabriel Alcalá-Cerraa, Juan
José Gutiérrez-Paterninab
Departamento de Neurocirugía, Universidad de Cartagena, Colombia.
b
Departamento de Medicina, Universidad de Cartagena,
Colombia.
*Autor Correspondiente: Dr. Luis Rafael Moscote - Universidad de Cartagena, Cartagena de Indias, Colombia.
E-mail: [email protected]
a
RESUMEN
Agenesia de huesos craneales son
entidades poco comunes, usualmente
incompatible con la vida. La agenesia de huesos parietales ha sido muy
pocas veces reportada en la literatura.
Se presenta el caso de un neonato con
agenesia de huesos craneales asociado a hidrocefalia. El defecto craneal fue
manejado de manera conservadora. A
nuestro conocimiento presentamos el
primer caso de la literatura de agenesia congénita de huesos craneales e
hidrocefalia.
Palabras Claves: agenesia, huesos,
craneales, hidrocefalia
INTRODUCCION
La agenesia de los huesos craneales es un
evento raro e incompatible con la vida en la
mayoría de los casos. Hay muy pocos casos
reportados en la literatura comprometiendo la
región parietal (1). Reportamos un caso de
agenesia de huesos parietal bilateral, en un
neonato saludable. En los anteriores casos reportados en la literatura se presentaron agenesia de parietales exclusivamente y en un caso
un paciente con malformaciones múltiples.
Reporte de Caso
Recién nacido de sexo masculino, nacido por
parto por cesárea motivada por diagnostico
prenatal de hidrocefalia congénita. Madre de
24 años, producto de tercer embarazo. Control
prenatal por ginecólogo. No hay antecedentes
de utilización de drogas ni exposición a sustancias teratógenas. Parto por cesárea a las 37
semanas. Al nacer APGAR al minuto de 9/10
y a los 5 minutos de 10/10. 3.500 gramos. Activo, reactivo, se observo en región occipital
gran encefalocele, exoftalmos. Se realizo TAC
cerebral con reconstrucción 3D que evidencio
agenesia de huesos craneales, frontal parietal,
temporal y parcialmente occipital (ver Imagen
1). El paciente permaneció 7 días en la unidad
de cuidados intensivos neonatales, posteriormente al 10 día en TAC cerebral control se
evidencia fontanela hipertensa y se decide en
junta médica colocación de sistema de derivación ventrículo peritoneal de presión media
neonatal, (Biomed) Evolución pospoperatoria
satisfactoria (ver Imagen 2). El paciente ha
sido evaluado mensualmente por neurocirugía
sin datos de disfunción valvular.
DISCUSION
Los defectos congénitos craneales en la calvaria y los huesos parietales son condiciones
raras.
La comprensión de las anomalías en la formación del cráneo requieren la comprensión
del desarrollo normal del cráneo y su morfología. El crecimiento del cráneo es determinado en parte por el crecimiento del cerebro.
Al año, el cerebro alcanza a lograr el 90% de
su crecimiento y el 95% a los 6 años, cesando
prácticamente el crecimiento del mismo a los
7 años.
El neurocráneo es embriológicamente dividido en la bóveda (Calvaria) formada desde
hueso membranoso y el basicráneo originado
de cartílago. El desarrollo inicial del neurocráneo depende de la formación del cerebro
y las membranas que lo rodean incluyendo la
duramadre. La ausencia de cerebro resulta en
acalvaria. Las capas que rodean al cerebro son
derivados del mesodermo y el ectomesenquima de la cresta neural y se subdivide en una
capa interna endomeninx y en una externa ectomeninx. El ectomeninx se subdivide en capa
osteogenica externa en la cual los centros de
osificación forman los huesos craneales y la
Imagen 1. TAC con reconstruccion tridimensional que evidencia agenesia parietal bilater
Imagen 2. Paciente en posoperatorio de
derivación ventriculoperitoneal (2 meses),
se evidencia forma irregular de cráneo
elongado.
capa interna que constituye la duramadre. La
capa de endomeninx interna se convertirá en
su porción externa la aracnoides y la interna la
piamadre. Los centros de osificación formaran
los huesos frontal, parietal, porción escamosa
del occipital y porción escamosa del temporal, otras áreas se encargaran de formar las
suturas fibrosas y las fontanelas. La agenesia
de los huesos craneales es incompatible con
la vida, pues usualmente este tipo de anomalías se acompaña de alteraciones cerebrales.
Por otro lado defectos craneales asociados a
aplasia cutis congénita han sido reportados.
La etiología exacta no es conocida, pero se
ha sugerido que alteraciones en el gen MSX-2
pueden tener participación en las anomalías
relacionas con agenesia de parietales. Se ha
descrito también la agenesia de hueso frontal
en pacientes con mielomeningocele (2).
55
También hay reporte de agenesia de huesos
parietales (3). También agenesia de huesos
craneales asociados a síndromes craneofaciales. (4). Se han reportado agenesia de
huesos craneales en familias (5). El tratamiento de tal defecto puede ser quirúrgico o
conservador, en nuestro caso decidimos realizar manejo conservador. (6). Por otro lado defectos de huesos craneales se han asociado
a aplasia cutis congénita, donde la característica es la ausencia craneal bilateralmente y
localizado entre las fontanelas anterior y posterior (7). Para la resolución de la hidrocefalia
asociada al defecto craneal decidimos colocar
un sistema derivativo con respuesta favorable.
Nuestro caso es el primero que reporta la asociación de Agenesia bilateral de parietales e
hidrocefalia.
ABSTRACT
The absence of the cranial bones is a
rare entity usually incompatible with
life. Agenesis of parietal bones has
been rarely reported in the literature. A
case of a neonate with bilateral parietal
agenesis associated hydrocephalus is
reported. The cranial defect was managed conservatively. To our knowledge
we present the first case of congenital
agenesis of the parietal bone associated with hydrocephalus.
CONCLUSION
La agenesia de huesos parietales congénita
es un evento raro. La asociación de agenesia
de huesos parietales con otras malformaciones pocas veces ha sido descrita en la literatura. Los mecanismos moleculares que son
el sustrato de esta inusual entidad son pocos
conocidos. Por su rareza y complejidad estos
casos se constituyen en un reto para los pediatras y los neurocirujanos pediátricos.
http://www.youtube.com/AMPRTube
y
http://asocmedpr.org/TV.aspx
los canales de video de la
BIBLIOGRAFIA
Asociación Médica de
1. A K Sharma, S K Kothari, L D Agarwal and A Sharma
Agenesis of the skull bones Pediatr Surg Int 17(5-6):4524 (2001)
2. Nayak PK, Mahapatra AK Frontal Bone Agenesis
in a Patient of Spinal Dysraphism Pediatr Neurosurg
2006;42:171–173
3. Sela M, Sahar A, Lewin-Epstein J.Agenesis of parietal
bones with restoration of the cranial vault. Case report. J
Neurosurg. 1979 May;50(5):674-6.
4. Spear GS.Parietal bone agenesis with gracile bones
and splenic hypoplasia/aplasia: clinico-pathologic report
and differential diagnosis with review of cranio-gracile
bone syndromes, "osteocraniostenosis" and Kleeblattschädel. Am J Med Genet A. 2006 Nov 1;140(21):2341-8.
5. Zabek M. Congenital absence of the parietal bones in
a family.Wiad Lek. 1987 Jan 1;40(1):33-8.
6. De Heer IM, Van Nesselrooij BP, Spliet W, VermeijKeers C. Parietal bone agenesis and associated multiple
congenital anomalies. J Craniofac Surg 2003; 14(2): 1926
7. Leboucq N, Montoya y Mártínez P, Montoya-Vigo F,
Catan P.Aplasia cutis congenita of the scalp with large
underlying skull defect: a case report. Neuroradiology.
1994 Aug;36(6):480-2
56
Puerto Rico orientados a los
profesionales de salud
con material educativo y de
investigación.
Suscríbase gratis
Publique sus trabajos
Estudie en su oficina u hogar
Review Article/Artículo de Reseña
57
ABSTRACT
Hashimoto’s encephalopathy (HE) is a rarely recognized neurocognitive syndrome
that is associated with thyroid autoimmunity. It is more common in women. HE is diagnosed when patients present with nonspecific neurological symptoms associated to
elevated titers of antithyroid antibodies and
normal or abnormal thyroid function tests.
Other neurologic disorders must be ruled
out before diagnosis can be established.
HE is associated to nonspecific EEG abnormalities as well as elevated cerebrospinal
fluid proteins and nonspecific white matter changes. The pathophysiology of HE
is unknown but an autoimmune etiology is
strongly supported. HE responds to corticosteroids and immunosuppressive therapy, further supporting an autoimmune etiology. A high index of clinical suspicion must
be present in order to promptly recognize
and treat this disease.
Index words: Hashimoto, encephalopathy,
underdiagosed, clinical
Hashimoto’s
Encephalopathy:
An underdiagnosed
clinical entity
José Hernán Martínez MDa, Oberto Torres MDa,
Michelle M. Mangual MDb*, Coromoto Palermo MDa, Carlos Figueroa MDa, Mónica Santiago MDa, María de Lourdes Miranda MDa, Eva
González MDa
Endocrinology Department, San Juan City Hospital, San
Juan Puerto Rico.
b
Internal Medicine Department, San Juan City Hospital,
San Juan, Puerto Rico.
*Corresponding author: Michelle M. Mangual MD - Caminos Verdes 6501 Carr 844 Apto 310 San Juan, Puerto
Rico 00926. Email: [email protected]
a
INTRODUCTION
The encephalopathy associated with autoimmune thyroid disease (EAATD), also named
Hashimoto's encephalopathy (HE) is an uncommon syndrome usually associated with
Hashimoto's thyroiditis, although fourteen
EAATD patients with Graves' disease (GD)
have also been reported (1). Originally described in 1966 by Brain et al., who reported
a case of a 63-year-old man with hypothyroidism, multiple episodes of encephalopathy, stroke-like symptoms, and Hashimoto’s
thyroiditis confirmed by elevated antithyroid
antibodies (2), it remains a somewhat controversial disorder that is characterized by neurological and psychiatric symptoms, high levels
of anti-thyroid antibodies, increased cerebrospinal fluid protein concentration, non-specific
electroencephalogram abnormalities, and responsiveness to the corticosteroid treatment in
patients with an autoimmune thyroid disease.
PATHOPHYSIOLOGY
The exact mechanism of Hashimoto's encephalopathy is not established. It does not seem to
be directly related to thyroid functional status.
Several mechanisms, like cerebral autoimmune
vasculitis disrupting the cerebral microvasculature with focal or global brain hypoperfusion, cerebral tissue-specific autoimmunity
with immune complex deposition with or without demyelination, and neuronal dysfunction
secondary to brain edema have been thought
to be involved in the pathogenesis (3,4,5,8).
Some facts that point toward an autoimmune
vasculitis are the identification of antigens
like α-enolase and a 36-kDa protein present
in biopsies of cerebral cortex in patients with
EAATD but their direct relationship is still not
established with the pathogenesis of this entity
(9,10) (see Table 1). Most patients with EAATD
respond to corticosteroids or other immunosuppressive therapies (11). Anti-thyroperoxidase (TPO) and anti-thyroglobulin (TG) antibodies have been often detected in the CSF
of EAATD patients but their possible role in
the pathogenesis has not been defined (1,8).
A higher frequency in women has been found.
A series identified that seven of eight patients
had HLA B8 DRw3 haplotypes compared with
30 percent of a control population (14). Associations with other autoimmune disorders (myasthenia gravis, glomerulonephritis, primary
biliary cirrhosis, splenic atrophy, pernicious
anemia, and rheumatoid arthritis) have been
reported (15). A review has suggested that
EAATD is a recurrent form of acute disseminated encephalomyelitis (ADEM) with a presumed
T-cell mediated lymphocytic vasculopathy
accompanied by blood-brain barrier breakdown (14).
A toxic effect of increased thyrotropin-releasing hormone (TRH) on the central nervous system has been proposed, as some patients appear to improve with thyroid supplementation
despite being euthyroid, but this is usually not
the rule (6,7).
The relationship between Hashimoto's thyroiditis and EAATD is unclear because elevated
titers of antibodies are prevalent in the general
healthy population, occurring in 2 to 10 percent
of young adults and 5 to 20 percent of older
adults. Nevertheless, anti-TPO antibodies are
present in 95 to 100% of cases of EAATD, and
anti-Thyroglobulin antibodies in 73% without
a significant relationship between the type of
antibody present and the neurological finding
(see Table 1).
EPIDEMIOLOGY
The estimated prevalence of HE was found to
be 2.1 per 100,000 as demonstrated in an epidemiologic study (15). Nevertheless, a review
published in 2006 showed that there were only
121 published cases of Hashimoto's encephalopathy (16). Thus, this syndrome may be under recognized. Women are more commonly
affected than men, at a ratio of approximately
four to one (7).
CLINICAL MANIFESTATIONS
The initial presentation of EAATD may be
acute or sub-acute (3,11) and the course could
be progressive or relapsing (17,18).
Approximately 25 percent of patients follow a
pattern of multiple, recurrent, focal stroke-like
neurologic deficits with cognitive dysfunction
and alteration in consciousness (3). Other
Table 1: Facts supporting a posible autoinmune vasculitis.
Table 2: Clinical Manifestations
58
symptoms that could be present are: psychosis with paranoid delusions, visual hallucinations, behavioral changes (16), seizures
that could be focal or generalized, myoclonus, language impairment (8,19). Less frequently, symptoms of cerebellar dysfunction,
extrapyramidal alterations like chorea, isolated myelopathy, polyneuropathy and amyotrophy can be found (20,21,22) (see Table 2).
Criteria for diagnosis
Presence of encephalopathy and elevated antithyroid antibodies in the absence of a central nervous system (CNS) infection, tumor, or
stroke (3) (refer to Figure 1)
Table 3: Differential Diagnosis.
Figure 1: Diagnostic Criteria.
59
DIFFERENTIAL DIAGNOSIS
Clinical entities that should be differentiated
from EAATD are illustrated in Table 3. A condition that might resemble some of the clinical
manifestations for EAATD is Creutzfeldt-Jacob disease (CJD). The presence of behavioral abnormality, myoclonic jerk, and walking difficulty may simulate CJD in which the
EEG reveals periodic discharges as compared with EAATD that presents a pattern of
diffuse slowing. The dramatic improvement
in clinical symptoms and normalization of
EEG following corticosteroid further rules out
the possibility of CJD. Any disease associated with a syndrome of delirium or rapidly
progressive dementia may be confused with
Hashimoto’s encephalopathy (see Table 3).
LABORATORY FINDINGS
As stated above antithyroid antibodies are an
essential laboratory feature of EAATD. Anti(TPO) antibodies are present in 95-100% of
cases and anti-Tg in 73%. Antibodies against
NH2-Terminal of α-enolase also has been
found in 44% of a series of 84 cases, but a
direct relationship has not been established
between the type of antibody present and the
neurological findings (3,16,33).
Anti TPO and anti Tg antibodies were also
found in a case series in the cerebrospinal
fluid in 9 of 12 patients with EAATD (15), but
in other study antithyroid antibodies were not
present (8). Thyroid functional status ranges
from hypothyroidism to hyperthyroidism and
euthyroidism (3,16).
Cerebrospinal fluid could present elevated
protein levels ranging from 48 to 298 mg/dl in
75% of patients. A mild lymphocytic pleocytosis is present in 10 to 25 percent of patients;
less common findings are Elevated 14-3-3
protein, and the presence of oligoclonal bands
(1,3,16). Nonspecific slow wave activity has
been found on electroencephalogram in 90%
of patients (1,3,23). Magnetic resonance imaging (MRI) is usually normal, but may show
nonspecific hyperintense non enhanced white
matter changes that have been reported to
have regression after treatment (1,3). Meningeal enhancement has been reported (11,
34). Cerebral angiography, when performed is
normal (6). Single photon emission computed
tomography (SPECT) may show focal, multifocal, or global hypoperfusion (3).
C-reactive protein, erythrocyte sedimentation
rate, and mild elevations of liver enzymes have
been found in some patients (23).
TREATMENT
The mainstay treatment of EAATD is corticosteroid therapy but optimal doses have not been
established because case’s paucity. Intravenous high methylprednisolone (1 gram/day)
doses have been used without proved benefit
when compared with oral steroids whose doses have ranged from 50 to 150 mg per day (6,
24). Ninety to ninety eight percent of patients
respond to steroid therapy over a few months
from which 90 percent of cases stay in remission after discontinuation of treatment. The duration of this syndrome has been reported from
2 to 25 years, but the length of treatment and
the rate of titration are usually made following
clinical response (25). There is a better evolution for cases of relapsing-remitting type compared to the progressive type with a few cases
of irreversible cognitive deficit in the later (6).
Residual cognitive impairment occurs in about
25 percent of patients with long-standing untreated disease (14,26).
Patients that do not respond to steroids relapse after discontinuation or tapering down
these agents. Those patients that do not tolerate steroid therapy have been treated with
other immunosuppressive agents like azathioprine, cyclophosphamide and methotrexate (8,
14, 24, 27). There are also reports of clinical
improvement with intravenous immunoglobulin
and plasmapheresis (28, 29, 30, 31, 32).
Treatment should also address thyroid dysfunction and control of seizures (14).
CONCLUSION
Hashimoto’s encephalopathy is an unusual
neurologic disorder. The etiology, pathogenesis and histologic characteristics remain
unclear. EAATD frequently presents with a
myriad of neurocognitive symptoms and normal findings in several different examinations.
It is an important diagnosis to be considered
in a patient with encephalopathy of unknown
origin, especially in patients with associated
autoimmune thyroiditis. A high index of clinical suspicion must be present in order to adequately identify and treat this steroid responsive disease without delay. It is essential for
general internal medicine, family medicine and
general physicians to recognize this uncommon disease given that usually they have the
initial encounter with these patients. An autoimmune etiology should be considered in a
patient with encephalopathy. Once a patient is
found with antithyroid antibody positivity, subclinical hypothyroidism or clinical hypothyroidism the diagnosis can be made and treatment
should be started immediately.
60
REFERENCES
1. Tamagno G., Celik Y., Simó R., et al. Encephalopathy
associated with autoimmune thyroid disease in patients
with Graves’ disease: Clinical manifestations, follow-up,
and outcomes. BMC Neurol. 2010; 10: 27.
2. Brain L., Jellinek EH., and Ball K. Hashimoto’s disease
and encephalopathy. Lancet 1966; 2:512.
3. Chong JY., Rowland LP., and Utiger RD. Hashimoto encephalopathy: syndrome or myth? Arch Neurol
2003;60:164.
4. Forchetti CM., Katsamakis G., and Garron DC. Autoimmune thyroiditis and rapidily progressive dementia:
Global hypoperfusion on SPECT scanning suggest a
possible mechanism. Neurology 1997; 49:623.
5. Caselli RJ., Boeve BF., Scheithauer BW., et al. Nonvasculitic autoimmune inflammatory meningoencephalitis (NAIM): a reversible form of encephalopathy. Neurology 1999; 53:157.
6. Kothbauer-Margreiter I., Sturzenegger M., Komor J.,
et al. Encephalopathy associated with Hashimoto Thyroiditis: diagnosis and treatment. J Neurol 1996;243: 585.
7. Peschen-Rosin R., Scahebet M., and Dichgans J.
Manifestation of Hashimoto’s encephalopathy years before onset of Thyroid disease. Eur Neurol 1999;41:79.
8. Shaw PJ., Walls TJ., Newman PK., et al. Hashimoto’s
encephalopathy: a steroid-responsive disorder associated with high anti-thyroid antibody titers-report of five
cases. Neurology, 1991; 41: 228-233.
9. Ochi H., Horiuchi I., Araki N., et al. Proteomic analysis of human brain identifies alpha- enolases as novel
auto antigen in Hashimoto’s encephalopathy. FEBS Lett,
2002; 528:197-202.
10. Oide T., Tokuda T., yazaki M., et al. Antineuronal autoantibody in Hashimoto Encephalopathy: Neuropathological, immunohistochemical, and biochemical analysis of
two patients. J Neurol Sci 2004: 217:7-12.
11. Castillo P., Woodruff B., Caselli R., et al. Steroid-responsive encephalopathy associated with autoimmune
thyroiditis. Arch Neurol.2006;63 :197–202.
12. Cantón A., deFàbregas O., Tintoré M., et al. Encephalopathy associated to autoimmune thyroid disease: a
more appropriate term for an underestimated condition?
J Neurol Sci. 2000; 176:65–69.
13. Nolte KW., Unbehaun A., Sieker H., et al. Hashimoto encephalopathy: a brainstem vasculitis? Neurology.
2000; 54:769–770.
14. Chaudhuri A., and Behan Po. The clinical spectrum,
diagnosis, pathogenesis and treatment of Hashimoto’s
Encephalopathy (recurrent acute disseminated encephalomyelitis). Curr Med Chem 2003; 10:1945.
15. Ferracci F., Bertiato G., and Moretto G. Hashimoto’s
encephalopathy: epidemiologic data and pathogenetic
considerations. J Neurol Sci 2004; 217:165–168.
16. Feracci F., and Caenevale A. The neurological disorder associated with thyroid autoimmunity. J Neurol 2006;
253:975.
17. Marshall GA., and Doyle JJ. Long-term treatment
of Hashimoto’s encephalopathy. J Neuropsychiatry Clin
Neurosci. 2006; 18:14.
18. Vander T., Hallevy C., Alsaed I., et al. 14-3-3 protein
in the CSF of a patient with Hashimoto’s encephalopathy.
J Neurol 2004; 251:1273.
19. Sawka AM., Fatourechi V., Boeve BF., et al. Rarity of
encephalopathy associated with autoimmune thyroiditis:
a case series from Mayo Clinic from 1950 to 1996. Thyroid. 2002; 12:393–398.
20. Passarella B., Negro C., Nozzoli C., et al. Cerebellar subacute syndrome due to corticosteroid-responsive
encephalopathy associated with autoimmune thyroiditis (also called “Hashimoto’s encephalopathy”).Clin Ter
2005;156:13.
21. Selim M., and Drachman DA. Ataxia associated with
Hashimoto’s disease: progressive non-familial adult onset cerebellar degeneration with autoimmune thyroiditis.
J Neurol Neurosur Psychiatry 2001; 71:81.
22. Kastrup O., Masche M., Schlamann K., et al. Hashimoto encephalopathy and neuralgic amyotrophy-causal
link or chance association? Eur Neurol 2005; 53:98.
23. Gayatri NA., and Whitehouse WP. Pilot survey of
Hashimoto’s encephalopathy in children. Dev Med Child
Neurol. 2005; 47:556.
24. Boeve BF., Castillo PR., Caselli JR., et al. Steroidresponsive encephalopathy associated with thyroid autoimmunity: outcome with immunomodulatory therapy. J
Neurol Sciences 2001; 187:S441.
25. Henderson LM., Behan PO., Aarli J., et al. Hashimoto’s
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26. Castillo P., Weoodruff B., Caselli R., et al. Steroidresponsive encephalopathy associated with autoimmune
Thyroiditis. Arch Neurol. 2006; 63:197.
27. Thrush DC., and Boddie HG. Episodic encephalopathy associated with thyroid disorders. J Neurol Neurosurg Psychyatry. 1974; 37:696.
28. Jacob S., and Rajabally YA. Hashimoto’s encephalopathy: steroid resistance and response to intravenous
immunoglobulins. J Neurol Neurosurg Psychiatry. 2005;
76:455.
29. Nieuwenhuis L., Santens P., and Vanwalleghem P.
Subacute Hashimoto’s encephalopathy, treated with
plasmapheresis. Acta Neurol Belg. 2004; 104:80.
30. Nagpal T., and Pande S. Hashimoto’s encephalopathy: response to plasma exchange. Neurol India. 2004;
52:245.
31. Boers PM., and Colebatch JG. Hashimoto’s encephalopathy responding to plasmapheresis. J Neurol Neurosurg Psychiatry. 2001; 70:132.
32. Drulovic J., Andrevic S., Bonaci-Nikolic B., et al.
Hashimoto’s encephalopathy: a long lasting remission
induced by immunoglobulins. Voinosanit Pregl. 2011;
68(5):452-4.
33. Mocellin R., Walterfang M., and Velakoulis D. Hashimoto’s encephalopathy. Epidemiology, pathogenesis and
management. CNS Drugs.2007; 21:10:799-811.
34. Ramalho J., and Castillo M. Hashimoto's encephalopathy. Radiology Case Reports. 2011; 6:445.
RESUMEN
Encefalopatía por Hashimoto (EH) es un
desorden neuro-cognocitivo raramente
conocido que se asocia a tiroiditis autoinmune. Este desorden es más común
en féminas. EH es diagnosticado cuando
los pacientes se presentan con síntomas
neurológicos no específicos asociado
con niveles elevados de anticuerpos antitiroideos y prueba de función tiroidea normal o anormal. Otros trastornos neurológicos se deben descartar antes de establecer
el diagnóstico. EH está asociado con cambios no específicos en el electroencefalograma y en la materia blanca del cerebro,
además de proteínas elevadas en el líquido cefalorraquídeo. La patofisiología de la
encefalopatía por Hashimoto es desconocida pero estudios sostienen que puede
estar asociado a un origen autoinmune.
La EH responde a la terapia con esteroides y agentes inmunosupresores lo cual
sostiene aún más la etiología autoinmune.
Se debe tener un alto índice de sospecha
clínica en lugar de reconocer y tratar esta
condición con prontitud.
61
62
Epidemiology of
coronary heart disease:
The Puerto Rico heart
health program
Mario R. García-Palmieri MDa*
Department of Cardiology, School of Medicine, University of Puerto Rico.
*Corresponding author: Mario R. Garcia Palmieri MD
– Department of Cardiology, UPR School of Medicine,
Puerto Rico Medical Center, Rio Piedras, Puerto Rico
00936. E-mail: [email protected]
Presented on July 2012 at the XIX Puerto Rican Congress of Cardiology sponsored by the PR Society of Cardiology at the Gran Melia Resort in Rio Grande. This
study was supported by contracts No. PH43-63-620 and
NOHV-42902 of the National Heart Institute of the U.S.
Public Health Service.
a
INTRODUCTION
Coronary Heart Disease (CHD) has been
the main cause of death in Puerto Rico and
most countries of the world for over the past
50 years. The study of factors that might predispose to the development of CHD has been
studied since the beginning of the 20th century.
Clinical observations revealed that male sex,
increase in age, elevated serum cholesterol,
elevated blood pressures were possible factors in subjects with CHD when compared with
those free of disease. A possible association
of physical inactivity, obesity and presence of
diabetes with the illness were also mentioned
in early publications.
It was considered that it was essential to conduct studies with an epidemiological focus in
specific populations in which all subjects would
be examined. Those individuals found to be
free of disease would be evaluated periodically for a period of years to identify which factors
were present in those that developed CHD that
were not present in those that did not develop
CHD to help identify risk factors.
The first prospective epidemiological study related to coronary heart disease was conducted in Framingham. It included the male residents of Framingham, Massachusetts in the
years 1949-1950 that were in the age group
45-64 years and were born between 1890 and
1920 that agreed to serve as volunteers for
the study. Over 60% of the males enumerated
Editorial Article/Artículo Editorial
ABSTRACT
Coronary heart disease (CHD) remains
as the main cause of death in most
countries of the world including Puerto
Rico. Due to the importance of gathering knowledge regarding the harmful
effects and risk factors associated with
the development of CHD some basic information is reviewed to stimulate the
institution of measures for reduction of
the prevalence of clinical CHD and its ultimate consequences. Special attention
is given in the manuscript of the Puerto
Rico Heart Health Program conducted
in men aged 45-64 residing in four rural
and three urban areas. The Puerto Rico
and the Honolulu Study confirmed the
initial publication on the epidemiology
of coronary heart disease by the Framingham study. The presentation of some
data collected among the three studies
strengthen the message of avoiding the
development of CHD by installing preventive measures for control and reduction
of the risk factors. Concurrent data obtained in the three studies is presented.
Although the degree of the involvement
of the populations is higher in Framingham than in Puerto Rico and Honolulu,
the deleterious effects of specific risk
factors are harmful in all the three populations. Difference in the prevalence of
risk factors among the urban and rural
males in Puerto Rico is also illustrated. It
is our hope that more intense measures
be instituted in Puerto Rico at all levels
in order to control risk factors and reduce the incidence of coronary disease
in Puerto Rico.
Index words: epidemiology, coronary,
heart, disease, Puerto Rico
collaborated. The description and details of
such study have been extensively described
in multiple scientific publications (1-4). Only
some aspects related to this study will be presented here.
Findings pointing to a significant relationship of
elevated serum cholesterol, high blood pressure, cigarette smoking, advancing age and
other possible factors were established by the
Framingham Study. As the study included
only a North American population the NIH was
interested in receiving proposals for conducting similar prospective epidemiological studies
in other populations.
The Faculty of the Department of Medicine
of the School of Medicine of the University of
Puerto Rico made a proposal including Puerto
Rican Hispanic men born between 1900 and
1919. Another proposal came from the Honolulu Study including men of Japanese ancestry
residing on the island of Oahu, Hawaii born between 1900 and 1919.
The Puerto Rico Heart Health Program (5,6,7)
This was a prospective epidemiological study
on coronary heart disease (CHD) and its risk
factors conducted in 9724 rural and urban
males by the Department of Medicine of the
School of Medicine of the UPR at the North
East Medical Region under the administration
of our School of Medicine and supported by
the National Institute of Health. It started in
1965 and lasted till 1985. Besides the initial
examination, which lasted almost 3 years, all
subjects were subsequently examined at 2.5,
5.25 and 8.25 years intervals. Each examination cycle lasted 3 years.
The census authorities in the selected areas,
in order to identify and enumerate all male
residents, conducted a house-to-house census. A total of 12,154 men were enumerated
with the goal of examining 80% of all enumerated subjects in all study areas. A total of 9824
males, representing over 80% in each one of
the seven selected areas were included and
examined. The census in 1965 had revealed
that in Puerto Rico there were about two urban residents per each rural one. The sample
for the study followed that distribution and was
designed to include two urban versus one rural male. It was conducted in four rural areas
of the towns of Barranquitas, Comerio, Corozal and Naranjito and three urban areas in the
towns of Bayamón, Carolina and Guaynabo
(5,6,7) (See Figure 1).
Of the 9724 males enumerated and examined
8793 were confirmed on a thorough initial examination to be in the 45-64 age group. All
were completely examined and 8254 were
found to be free of CHD (6). The number of rural and urban males by age groups 45-54 and
55-64 found to be free of CHD in the Puerto
Rico Heart Health Program is illustrated in Table 1.
The information obtained consisted of 255 different variables in all the subjects. It included:
•
Social interview, education, occupation,
smoking habits, physical activity (8).
63
Table 1. PUERTO RICO HEART HEALTH
PROGRAM MALES AGED 45-64 FREE OF
CHD
•
•
•
•
•
•
•
Medical history and physical examination.
Twelve lead electrocardiogram (9).
Pulmonary vital capacity.
Urine for sugar and albumin.
Hematocrit.
Blood serology, blood sugar.
Serum cholesterol, triglycerides and lipoprotein electrophoresis.
All the information obtained in each individual
was entered in pre-coded forms to be analyzed by computers (10). The specific procedures followed in all the determinations have
been included in multiple references published
on the study. Multiple quality control measures
of the laboratory procedures were maintained
including periodic exchange of samples with
the National Communicable Disease Center
(NCDC) in Atlanta, Georgia and interchange
of samples with NIH laboratories. All the study
personnel including physicians, nurses, dietitians, social workers, secretaries and laboratory technician had special training on the jobs
to be performed in order to insure internal consistency in the data obtained.
The findings of the PRHHP from 1965 to 1985
lead to 56 different scientific publications that
were published in 26 different recognized medical scientific journals listed in the Index Medicus.
In this article we will not enter into all specific
details of the study in which voluminous information was obtained and published. The main
purpose of this review is to present some of the
salient features of the study. In the included
references of publications related to the study
included the readers would find further specific
details.
An age-adjusted mean value of specific findings
of urban and rural males free of CHD at the initial examination (6, 11) is illustrated in Table 2.
The table obtained illustrates some factors that
are more frequent in urban residents and other
that are more frequent in the rural males.
Cigarette smoking intensity, relative weight,
blood pressure, prevalence of diabetes, serum
cholesterol and triglycerides levels were higher
in urban males. Physical activity, higher pulmonary vital capacity and bradycardia were most
frequently encountered in rural men.
Figure 2 shows the prevalence of systolic blood
pressure of 160 mm Hg or above and diastolic
blood pressure of 95 mm or above as well as
heart rate of less than 60 beats per minute in
both age groups in the urban and rural men (12,
13). Irrespective of age in both groups blood
pressure were higher in the urban and bradycardia of < 60 was most frequent in rural men.
In both age groups the prevalence of diabetes
was higher in the urban group (12, 13) (See Figure 3).
A very thorough follow-up of all study subjects
was conducted including mortality rates for a
period of 12 years. The mortality rate in the
initial age groups 45-54 and 55 to 64 of urban
and rural men was established at 2.5, 5¾, 8.5
and 12 years (14). This is illustrated in Figure 4.
64
Table 2 Age-adjusted mean values of characterics by residence at the initial examination on subjects free of CHD ( 6,11 ).
As shown in the figure the occurrence of coronary deaths per 1000 increased as the follow
up time increased. In each of the corresponding residential areas (urban or rural) the older
subjects had a higher mortality rate. The higher mortality rate due to CHD observed in urban
versus rural males was present in both the 45
to 54 age group as well as in the 55-64 group.
An important item, among the many included
in the study, was the inclusion of a dietary interview using the 24-hour recall method. Specially trained dietitians did it in all subjects.
This led to multiple publications (15). This also
helped in the study of differences and similarities among the urban and rural males and also
in the conduction of comparisons with other
studies such as Framingham and Honolulu
(16).
External Comparisons
Baseline 24-hour dietary recalls form men
aged 45 to 64 who had no evidence of CHD
were obtained in Framingham, Puerto Rico
and Honolulu (16). It included 859 men from
Framingham, 8218 from Puerto Rico, and
7272 from Honolulu. These men were followed
up for 6 years for CHD appearance. Important information concerning starch and alcohol
consumption revealed by this study has been
published (16).
In the dietary study of the three populations a
higher caloric intake correlated to less CHD
deaths. In Puerto Rico and Honolulu a higher
intake of starch was related to less CHD death.
A higher relative weight was related to more
CHD deaths and more alcohol intake was associated to less CHD deaths (16).
In another study we compared the data obtained
in the Framingham study, the PRHHP and the Honolulu Study (18). For this study we used quality control by standardized procedures such as
a common set of serum pools supplied by the
Communicable Disease Center in Atlanta in order to have comparable data. In all laboratory
procedures performed at the Puerto Rico Heart
Health Program multiple laboratory quality control
measures were maintained (19). Identical criteria
were used for diagnosis of CHD, EKG interpretation etc., in order to have valid comparisons.
Serum cholesterol was related to CHD in the three
studies as well as systolic blood pressure but at
corresponding levels of systolic blood pressure
and serum cholesterol the probability of CHD in 2
yr/1000 was higher in Framingham than in Puerto
Rico and Honolulu (18). Among the data collected
in different studies addressing the relation of risk
factors with the development of CHD, elevation of
systolic blood pressure and elevated serum cholesterol have been consistently present. Such factors were risk factors strongly related to the development of CHD in the Framingham, PRHHP and
Honolulu studies (6). See Figures 6 and 7.
In the autopsies performed in the PRHHP
study subjects the pathological material was
evaluated in a very rigorous form by multiple pathologists specially trained for detailed
analysis of coronary arteries. The studies
conducted in 139 autopsies of study subjects
demonstrated that the percentage of elevated
coronary lesions in the coronary arteries was
higher in those subjects with higher systolic
blood pressures (17). Figure 5 demonstrates
the percentage of involvement of elevated lesions in the coronaries according to systolic
blood pressure levels of the subjects prior to
their death. Higher percentage of involvement
of the coronaries by elevated lesions means a
more advanced involvement of the coronaries
by the atherosclerotic process.
65
Figure 6 shows the probability of CHD in 2
years /1000 in the three studies in subject’s
aged 55 from the three studies is illustrated
(6). The probability of CHD development in 2
years in presence of a higher systolic pressure
occurred in the three studies although it was
most prominent in Framingham.
Figure 7 depict the probability of developing
CHD in 2 years /1000 in 55 year-old subjects in
the three studies according to the serum cholesterol level (6). The probability of development of CHD with a higher serum cholesterol
level occurred in the three studies. The deleterious effects of the two risk factors illustrated
in figures 6 and 7 especially in Framingham
and Puerto Rico were greater in the older men
than in the younger ones (6). The prevalence
of CHD was twice as great in Framingham, as
in Honolulu and Puerto Rico. CHD incidence
by ECG alone, by CHD death, or by both was
from 2 to 4 times as high in Framingham as in
Honolulu and Puerto Rico (6).
DISCUSSION
In spite of the significant advancements in the
diagnosis and management of CHD it is the
main worldwide cause of death including Puerto Rico. The Puerto Rico Heart health Program
conducted at the School of Medicine of the
University of Puerto Rico from 1965 to 1985
in the urban and rural areas of seven towns of
the Northeast Medical Region of our island revealed important findings concerning risk factors for CHD in Puerto Rico. It is important to
make all possible efforts to prevent the occurrence of CHD prior to its onset and complications.
of the world including some rich and prosperous countries such as the United States.
In order to prevent the development of CHD
a global effort worldwide, national and local,
including familiar, educational as well as and
medical measures must be instituted since
birth to control the risk factors that may precipitate the development of CHD and its deleterious effects.
In this manuscript we have included some salient features of the studies in Framingham,
Puerto Rico and Honolulu re-emphasizing the
need to maintain the awareness of the danger of risk factors in the development of CHD.
Basic references that can help the readers in
participating in efforts to prevent the development of coronary artery disease have been
presented. Once coronary artery disease has
developed it is mandatory to diagnose it early
and manage it accordingly.
Prospective epidemiological studies designed
to include subjects without CHD followed up
for years until the disease develops have
identified a series of risk factors whose presence favors the development of the disease.
Among these are elevated serum cholesterol,
elevated systolic or diastolic blood pressure,
increase in age, cigarette smoking, physical
inactivity and obesity. Unfortunately preventive
measures to control these risk factors have not
been successfully developed in each country
The Framingham Study was the first epidemiological study that confirmed the danger of the
risk factors. The Puerto Heart Health Program
in Puerto Rico and the Honolulu Study provided confirmatory evidence of the relationship of
risk factors to the development of CHD. Subsequent interventional limited studies have
demonstrated the beneficial effect of the control and avoidance of risk factors in reducing
CHD occurrence.
Today, the most important approach to this
dangerous illness is to prevent the development of coronary artery disease. In order to do
so, early measures must instituted at all levels
to reduce, control and avoid those factors that
have been identified with the development of
CHD. All of us need to be involved in this effort.
66
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Risk Factors and Prevalence of coronary heart disease in
Puerto Rico Circulation 1970; 42: 541-549
14- García-Palmieri MR, Sorlie PD, Havlick RJ et al Urban-Rural differences in 12 year coronary heart disease
mortality: The Puerto Rico Heart Health Program. J Clin
Epidemiol 1988; 41: 285-292
15- García-Palmieri MR, Sorlie P, Tillotson MA. et al. Relationship of dietary intake to subsequent coronary heart
disease incidence: the Puerto Rico Heart Health Program.
Am J Clin Nutr 1980; 33: 1818 – 1827
RESUMEN
La enfermedad de las arterias coronarias
se mantiene como la causa número uno
de muerte en la mayoría de los países del
mundo incluyendo a Puerto Rico. Debido a
la importancia de conocer la relación de los
factores de riesgo con el desarrollo de la
enfermedad coronaria se presenta alguna
información básica sobre el tema para estimular el uso de medidas para reducir la
prevalencia de la enfermedad. Los tres estudios epidemiológicos principales relacionando factores de riesgo y la enfermedad
coronaria se llevaron a cabo en Framingham, Puerto Rico y Honolulu. Se presenta
atención especial a los resultados obtenidos en el Programa de Salud del Corazón
de Puerto Rico realizado del 1965 al 1985
en varones de 45-64 años de edad en cuatro áreas rurales y tres urbanas de nuestro
país. Se presentan además datos obtenidos concurrentemente en los tres estudios.
Los factores de riesgo son dañinos en los
tres estudios pero su severidad es mayor
en Framingham. Se presenta además diferencias en la prevalencia de factores de
riesgo entre el puertorriqueño urbano y el
rural. Esperamos que este artículo de reseña ayude a que se tomen las medidas en
Puerto Rico para controlar o disminuir a los
factores de riesgo para lograr reducir la enfermedad coronaria en nuestra isla.
67
La Asociación Médica
de Puerto Rico
abre sus puertas a:
Investigadores
Estudiantes
Escritores
y
profesionales de la
salud
que quieran
presentar sus
proyectos y
publicarlos
Comuníquese con la
División de Informática
[email protected]

Untitled - Asociacion Medica de Puerto Rico

Transcription

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