Journal of Medicine Vol 11 (July - December 2015)

ISSN - 0975 - 9662
Vol. 11, NO: 2
July - Dec 2015, Page 1- 44
Mechanism of Stroke Progression
PET Imaging In Epilepsy
Chronic Pancreatitis
Malignant Hyperthermia
www.adwa.in
Vol. 11, NO: 2
July - Dec 2015, Page 1 - 44
Editorial
02 Gift of Healing
H. Kumar
26 A Study on Obstetric and Ultrasonographic
Parameters in Patients with Early Miscarriage
Parvathy Ganesan, Deepthi Sharma, Sudha.S,
Radhamany.K
03 Spiritual Message
Review Article
04 An Insight into Mechanism of Stroke Progression
Ajith Kumar.J, Vivek Nambiar, Gireesh Kumar,
Sreekrishnan T. P, Ajith.V, Naveen Mohan
08 SPECT & PET Imaging In Epilepsy – An Overview
S.Padma, P. Shanmuga Sundaram
Original Article
12 A Prospective Study to Determine the Efficacy of
CIMT in Infants with Erb's Palsy
Ravi Sankaran, Surendran.K, K.R Sundaram,
Priyavadhana.R
18 Mid-term follow up and Functional outcome after
Surgical fixation of Displaced Acetabular
Fractures – An Institutional experience
Melvin J George, Druvan.S.P, K.K.Chandrababu,
V.K.Bhaskaran
23 Predicting Clinical Outcome In Acute Ischemic
Stroke Based On TOAST Classification
Ajith Kumar J, Vivek Nambiar, Gireesh Kumar,
Sreekrishnan T. P., Ajith V, Naveen Mohan
31 Chronic Pancreatitis: Experience of the last 15
years in the Pancreas Clinic at AIMS
G. Rajesh, V. Balakrishnan
Case Report
34 Escape From Disseminated Melioidosis Of
Tropics: A Case Report And Literature Review
Naveen Mohan, Priya R. Menon, Gireesh
Kumar K.P, . Sreekrishnan T.P, Ajith Kumar J,
Bharath Prasad S, Ajith V, Krupanidhi
Karunanithi, Arun Kumar K.
38 A Rare Case of Malignant Hyperthermia
Shyam Sundar.P, Suresh Kumar.R, Anand
Kumar.A
41 Inadvertent Insertion of Ryle's Tube into the
Trachea Following Endotracheal Intubation
Mohammed kutty K, Deepa Mirium Varghese,
Mathew George, Gokuldas Menon
43 Titanium Elastic Nailing in Paediatric Fracture
Femur - A Case Report
S. Ravi Subramaniam, Krishna Kumar R.
Vol. 11, NO: 2
July - Dec 2015, Page 1 - 44
Editorial Board
Gift of Healing
H. Kumar
Patrons
Swami Amrita Swaroopananda Puri
Dr.Prem Nair
Dr.P.Prathapan Nair
Chief Editor
Dr.Harish Kumar
Editorial Board Members
Dr.Anand Kumar
Dr.Sudhindran
Dr.Unnikrishnan K.Menon
Dr.Ramakrishna P Venugopal
Dr.P.Sasidharan
Dr.Sheela Nampoothiri
Dr.Sanjeev K Singh
Dr.D.M.Vasudevan
Publicity Officer
Mrs. Gita Rajagopal
Design & Artwork
Varghese MM
Copyright
Although every possible care has been taken to
avoid any mistake and this publication is being sold on
condition and understanding that the information it
contains are merely for guidance and reference and
must not be taken as having the complete authority.
The Institution and The Editors do not owe any
responsibility for any loss or distress to any person, on
account of any action taken on the basis of this
publication. The copy rights on the material and its
contents vests exclusively with the publisher. Nobody
can reproduce or copy the prints in any manner.
2
In an era where technology is becoming increasingly dominant, the approach of physicians appears
to be changing. The availability of very sophisticated
imaging techniques, laboratory tests and genetic tests
had made diagnosis very precise. Newer designer drugs
with more specific actions are now available to target
each disease. Robotic surgery and other new less
invasive interventions have made surgical procedures
very precise reducing blood loss and complications
during surgery. All in all the new medical technology
available for patient care is really impressive and
effective.
However, there is still no substitute for a careful
history and a detailed physical examination by the
physician to elicit symptoms and signs which will lead
to a diagnosis. The scans and investigations should only
be used to compliment the physician's diagnosis. Even
in the matter of providing treatment, the compassion
and healing touch of the physician, though now greatly
undervalued, is far superior to any drug or therapy that
we can conjure up. Many patients feel that the mere
presence of the physician lifts their mood and reassures
them. A firm and kind “don't worry, we will get you
better” will work wonders if the physician is genuinely
compassionate. Unfortunately many young doctors
nowadays are slaves of technology to the point where
they will see the patient only after a battery of tests have
been done. How one can order an Echocardiogram or
MRI brain or CT chest even without seeing the patient,
let alone examining him, is beyond comprehension.
But unfortunately such an approach to practising medicine is on the increase.
We must be patient-centric in our approach. First
and foremost we must form a bond with the patients
through proper communication and examination and
only then must we unleash all the sophisticated technology at our disposal and that must be done judiciously to better the health of our patients.
Vol. 11, NO: 2
July - Dec 2015, Page 1 - 44
SPIRITUAL MESSAGE
Broaden Your Vision
As physicians we must be kind
and compassionate to our patients. Since this caring attitude is a
part of our job, it should be easy
for us to extend this compassion
to all other people with whom we
interact. Indeed, we should extend this attitude of love and compassion to all creatures around us
and to all of Nature. But very often
we get caught up in our own
private world and then we only
have concern for our own needs
and may be the needs of our
family. This makes our thinking
and outlook very restricted. We
may be nice people, but yet we
often tend to narrow down and
zone in an only ourselves and
hence miss the larger picture.
The following parable narrated
by Amma is a simple example of
this.
One day a lady was waiting for
her flight at an airport. She sat
down on a bench and began to
read a book. She had a packet of
biscuits in her handbag and was
thinking of having a few biscuits,
but she got immersed in reading
her book. She noticed that a pleasant young man sat down on the
same bench. The lady then saw that
the young man was helping himself
from her packet of biscuits which
was lying on the bench beside her.
She looked out of the corner of her
eyes and saw the young man help
himself to another biscuit. She was
irritated that he was helping himself
to her biscuits without her permission or invitation.
She kept glancing out of the
corner of her eye to see what he was
up to, and she became more and
more agitated each time the young
man took another biscuit. Her
peace of mind was gone. She was
unable to concentrate on her book.
Suddenly she saw that the young
man had picked up the biscuit
packet and held it up to her and
asked with a smile, “Would you like
to have one?”
The lady was furious. “He has
coolly helped himself to my biscuits
and now he has the cheek to ask me
if I want one” she thought. She
didn't reply to his enquiry, but
snorted in disgust and gave him a
dirty look and got up and went away,
thinking, “This fellow has no manners. Let the greedy pig have the rest
of my biscuits as well.”
Later on, after she had calmed
down and boarded her flight, she
opened her handbag and found her
packet of biscuits inside the bag–
unopened. Only then did she realise
that all along the young man was
eating his own biscuits and she needlessly got agitated thinking that they
were her biscuits. She felt ashamed at
her behaviour, especially when she
recollected how the young man had
offered her his biscuits and she got up
rudely and went away with-out
replying. “Wouldn't it have been a
much more pleasant experience if I
had shared the biscuits with him,
without worrying about whom they
belonged to?” she thought regretfully. After all they were only biscuits.
This is how our attachment to
objects and people that we think
belongs to us results in unnecessary
and endless stress and problems.
We should always concentrate on
giving, instead of accumulating.
3
Vol. 11, NO: 2
July - Dec 2015, Page 1 - 44
REVIEW ARTICLE
An Insight into Mechanism of Stroke Progression
Ajith Kumar.J, *Vivek Nambiar, Gireesh Kumar,
Sreekrishnan T. P, Ajith.V, Naveen Mohan
ABSTRACT
Early neurological deterioration following stroke is quiet common and is associated with significant mortality and morbidity.
Etiology of stroke is very well understood, whereas that of neurological worsening is different and not as clear. Vascular occlusion,
reocclusion of recanalised artery, rapid rise in intracranial pressure, hemorrhagic transformation are the various mechanisms for
stroke progression whereas good recruitment of collaterals is associated with recovery from an ischemic stroke. Earlier, clot
progression was attributed to neurological worsening but with the advent of MRI, it is now understood that failure of collaterals is
responsible for stroke progression.
Keywords: Stroke Progression, Early Neurological Deterioration, Mechanism of stroke progression.
INTRODUCTION
It is estimated that, annually, 15
million people worldwide suffer a
stroke. Of these, 5 million deaths
occur and another 5 million are left
permanently disabled1. Various studies have shown that early neurological worsening in acute ischemic
stroke is common; ranging from 20
– 40%2-5.
Various risk factors for stroke
have been well established. These
include high blood pressure, disorders of heart rhythm, smoking, high
blood cholesterol, physical inactivity, diabetes mellitus, end stage
renal disease & chronic kidney
disease6,7 .
Early neurological deterioration
following stroke is quiet common
and is associated with significant
mortality and morbidity. Etiology
for stroke is very well understood,
whereas etiology behind neurological worsening is not clear and is
different.
MECHANISM OF STROKE PROGRESSION
Several mechanisms have been
proposed for progression of stroke.
Various factors include failure of collaterals, occlusion of large arteries,
raised intracranial pressure, seizures and hemorrhagic transformation and inflammation.
Failure of collaterals
Occlusion of a major blood vessel
is one of the most important independent predictors of early neuroDepts. of Emergency Medicine and *Neurology,
AIMS, Kochi.
4
logical deterioration. Vascular occlusion leads to hypoperfusion of the
affected region, unless effective collateral circulation develops. Collaterals are native blood vessels connecting different arterial territories.
Initial clinical worsening is due to
synaptic dysfunction with preserved cell membrane integrity and is
potentially reversible with vessel
recanalisation8. Good recruitment
of collaterals helps in the rapid
recovery8,9.
Collateral status at baseline is an
independent determinant of clinical
outcome amongst patients with
acute ischemic stroke10.Studies
have shown that good collaterals at
baseline have small baseline infarcts when compared with patients
with intermediate and poor collaterals11. The rate of infarct growth
is also quicker in patients with intermediate collaterals and outcome is
improved in patients achieving
recanalization following thrombolysis11.
Diabetic microangiopathy and
chronic hypertension impair microvascular function, reducing the
potential for collateral development. Insufficient collaterals leads
to reduced oxygen delivery and
metabolic disturbance, aggravates
cellular damage by enhancing brain
edema and free radical injury9,12.
Cerebral oedema
Davalos et al demonstrated that
brain edema is an independent
factor for early neurological worse-
ning13. Raised ICP accounts for 19%
of cases of early deterioration in
ischemic stroke14. It is usually a complication of large intracranial artery
occlusion and large multilobar
infarction. Brain edema spreads in
concentric fashion and progressively reduces clinical function
without extension of the original
area of infarction15.
Life-threatening middle cerebral
artery infarction occurs in upto 10%
of all stroke patients. Werner et al
demonstrated that complete middle
cerebral artery territory stroke leads
to rapid development of space
occupying mass effect and most of
these patients developed herniation16. Derk et al & Scott et al also
demonstrated that patients with ≥
50% of middle cerebral artery territory stroke are at a high risk for developing fatal brain swelling17,18.
Hemorrhagic transformation
Hemorrhagic transformation in
ischemic stroke is common and ranges from small asymptomatic petechiae to a large hematoma with pressure effects8. Large parenchymal
hematoma is considered to be associated with adverse effects. As the
ischemia prolongs, there will be uncoupling of the astrocyte foot process from the endothelium and
blood brain barrier becomes porous.
Hence, the duration of ischemia is a
crucial factor in hemorrhagic transformation of infarcts.
Vincent et al demonstrated that the
risk of hemorrhagic transformation is
related to extent of cerebral ischemia19. They found that
patients with hypoattenuation in >33% of the middle
cerebral artery territory on baseline CT scan had higher
risk for hemorrhagic transformation19. Vincent et al also
analyzed the relationship of hemorrhagic transformation
and cardio-embolic stroke, and found that congestive
heart failure was associated with increased hemorrhagic
transformation, whereas atrial fibrillation and myocardial
infarction were not19. Lodder et al demonstrated that
confluent hemorrhages where more common in patients
with cardio-embolic stroke20 .
Vincet et al also demonstrated that risk for hemorrhagic transformation is higher in older patients
following rtPA19. There is higher incidence of hemorrhagic transformation in rtPA treated patients who had
aspirin before stroke19,21.
Re-occlusion of re-canalized artery
Early re-occlusion accounts for two thirds of deterioration following improvement in patients treated with
tPA22. Alexandrov demonstrated that occlusion occurs
in upto 34% of tPA treated patients with any initial recanalisation. He also found that re-occlusion occurs
more often in patients with earlier and partial re-canalization, leading to neurologic deterioration and high inhospital mortality22. However, he also observed that
patients with re-occlusion have better outcomes than
patient without any re-canalization22. A single cohort
study of acute tPA given in stroke patients showed an
early recurrent ischemia of 6%. Most of these patients
were having atrial fibrillation23.
Marta, et al demonstrated that clinical worsening
occurs in upto 12% of middle cerebral artery stroke
treated with tPA24. They demonstrated that stroke
severity at the time of admission and presence of extracranial carotid artery disease represent independent
predictors of early arterial re-occlusion after tPA induced re-canalization24. They also observed that stroke
severity represents the clinical surrogate of clot
burden24.
Experimental studies have demonstrated that effective delivery and distribution of tPA into the clot
accelerates fibrinolysis and that the fibrinolysis rate is
dependent on the pressure gradient to which the clot is
exposed25,26. Presence of an extracranial severe carotid
stenosis or occlusion leads to a regional decrease of
cerebral perfusion pressure, which may not only hamper MCA clot dissolution but also favor blood stasis,
increasing the likelihood of rethrombosis after incomplete re-canalization27. Furthermore, in vitro and animal
models had demonstrated that clots formed under
variety of biochemical and physical conditions exhibit a
differential susceptibility to lysis25,26. This could be one
of the possible mechanisms for re-occlusion following
re-canalisation with tPA.
Clots formed in arterial bifurcations had usually been
considered as platelet rich clots. The latter are resistant
to lysis and more prone for rethrombosis24. It is known
that the tPA itself promotes thrombosis by stimulating
the plasmin production, which activates platelets and
transform prothrombin to its active form. Thrombin has
also been demonstrated to mediate platelet activation
and to convert fibrinogen to fibrin. The activated
platelets secrete native plasminogen inhibitor 1, which
opposes the intrinsic fibrinolytic cascade and administrated tPA24. The presence of a platelet-rich clot probably enhances this mechanism as demonstrated in
patients with acute MI in whom an augmented platelet
aggregation was a powerful predictor of re-occlusion
after thrombolysis28. This could be another probable
reason for re-occlusion.
Seizures
Seizures account for neurological deterioration in
3% of patients with ischemic stroke with large cortical
infarct29. They lead to transient neurological worsening,
though prolonged partial seizures can lead to persistent
worsening30.
Inflammation
The cause for early neurological deterioration in
patients with lacunar infract is still unclear. Study done
by M. Castellanos, et al in a large series of patients with
lacunar infraction demonstrated that high levels of
inflammation is an independent risk factor for early
neurological deterioration and poor outcome31. Plasma
levels of inflammatory mediators interleukin-1,632,
Tumor necrosis alpha33 and Intercellular adhesion molecule-137 have been observed to increase after experimental brain ischemia.
They observed higher levels of inflammatory
molecules in patients with lacunar infractions located in
basal ganglia and brainstem than in those with white
matter infarctions31, so it was hypothesized that excitotoxicity and inflammation might represent sequential
and interacting processes in the progression of lacunar
stroke, particularly in areas in with high density of glutaminergic neurons31,34. This theory is supported by an
animal study done by Chaco, who demonstrated that
exposure of human fetal neuronal cells to the excitatory
aminoacid neurotransmitter, glutamate, for 6 days, resulted in a dose-dependent cell loss. Moreover they
demonstrated that TNF-alpha potentiating glutamate
toxicity was blocked by administering glutamate receptor antagonist35.
Interleukin synthesis in the brain is stimulated by
mechanical injury and it was demonstrated by Relton in
animal studies that neuronal death resulting from focal
ischemia is significantly inhibited in rats injected with a
recombinant interleukin-1 receptor antagonist, indicating that endogenous IL-1 is a mediator of ischemia and
excitotoxic brain36.
Recently, studies have shown that patients on aspirin
have less severe stroke38. De Cristobal et al demonstrated that aspirin has neuroprotective effect also, apart
5
An Insight into Mechanism of Stroke Progression
from the antiplatelet effect in animal studies39. The
former effect is due to inhibition of glutamate. Later,
they confirmed these findings in human studies. They
studied the levels of glutamate in patients presenting
with acute ischemic stroke and found that patients on
aspirin had lesser levels of glutamate and also treatment with aspirin at stroke onset has 97% risk reduction
for early neurological deterioration40 .
Recurrent Stroke
Patients with acute ischemic stroke were associated
with recurrent stroke during initial first week and were
associated with early neurological worsening41,42. Kang
et al demonstrated that recurrent stroke was most
frequently seen among patients with large artery
atherosclerosis42.
Clot Progression
Early neurological deterioration in acute ischemic
stroke had been attributed to clot progression in the
past44,15. But studies of early MRI in acute stroke have
shown large vessel occlusion and failure of collaterals
rather than clot progression as the main mechanism of
occlusion of early neurological deterioration43,44.
Cortical Spreading Depression
These are small depolarization waves at the periinfarct and injury areas which continue for a varying
period of time and causes progressive damage45. It is
very common in massive hemispheric infarcts. Further
research is ongoing to tap the potential therapeutic
option in this aspect.
CONCLUSION
Vascular occlusion, re-occlusion of a re-canalised
artery, rapid rise in intracranial pressure, hemorrhagic
transformation are all associated with stroke progression whereas good recruitment of collaterals is
associated with recovery from an ischemic stroke.
Further research is needed in this field to identify the
factors responsible for stroke progression and to develop therapeutic options to prevent stroke progression.
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28. Nordt TK, Moser M, Kohler B, et al. Augmented platelet
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29. Johnston KC, Li JY, Lyden PD, et al. Medical and neurological
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31. Mar castellanos, Jose Castillo, Maria M. Garcia, et al. Inflamamtion-mediated damage in progressing lacunar infractions:A potential
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32. T. Liu, PC McDonnell, P R Young, et al. Interleukin-1 beta mRNA
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38. James C. Grotta, Noreen A. Lemak, Howard Gary, et al. Does
platelet antiaggregant therapy lessen the severity of stroke ?.
Neurology May. 1985;35:632-6.
39. De Cristobal J, Moro MA, Davalos A, et al. Neuroprotective effect
of aspirin by inhibition of glutamate release after permanent focal
cerebral ischaemia in rats. J Neurochem. 2001 Oct; 79(2):456-9.
40. Castillo J, Leira R, Moro MA, et al. Neuroprotective effects of
aspirin in patients with acute cerebral infraction. Neurosci Lett. 2003
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41. Weimar C., Mieck T, Buchthal, et al., German Stroke Study
Collabration. Neurologic worsening during the acute phase of
ischemic stroke. Arch Neurol. 2005 Mar,62(3):393-7.
42. Kang DW, Latour L.L., Chalela JA, et al. Early ischemic lesion
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7
Vol. 11, NO: 2
July - Dec 2015, Page 1 - 44
SPECT & PET Imaging In Epilepsy – An Overview
S.Padma, P. Shanmuga Sundaram
ABSTRACT:
Epilepsy is one of the most prevalent neurological disorders worldwide. There are more than 10 million epileptic patients in India
alone. Antiepileptic drugs are used to control seizures, but in about 30% of patients, they are refractory. These medically
intractable patients are candidates for surgical treatment in order to achieve better seizure control. The single most important
determinant of a successful surgical outcome is patient selection. This requires detailed pre-surgical evaluation to characterize
seizure type, frequency, localization of seizure focus, psychosocial functioning and degree of disability in order to select the most
appropriate treatment from a variety of surgical options. Molecular imaging with ictal and interictal single-photon emission
computed tomography (SPECT) as well as positron emission tomography (PET) rank among the established functional imaging
tests for the pre-surgical evaluation of patients especially with temporal lobe epilepsy (TLE). In TLE, the sensitivity of these methods
is found to be excellent, in particular if a multimodality platform is used, which integrates the functional imaging with
morphological information of magnetic resonance imaging (MRI), but is lower in extra-temporal lobe epilepsy. Functional
imaging with SPECT and PET actually reflects the seizure-related changes of cerebral perfusion, glucose metabolism and
neuroreceptor status.
Key words: Cerebral perfusion; SPECT; PET; Ictal; interictal study.
INTRODUCTION
Patients unresponsive to anticonvulsant therapy may be candidates for surgical treatment. The
pre-surgical evaluation of epilepsy
patients1 is a multiphase process,
involving noninvasive tests such as
Electroencephalogram (EEG), neuropsychology assessments of verbal
and non-verbal memory, MR, and
ictal / interictal SPECT/PET.
Most partial complex seizures
originate in the temporal lobe. Unfortunately scalp EEG often fails to
accurately localize the seizure
focus. Depth EEG is much more
accurate, but it is invasive, requiring
a craniotomy. Also, it suffers from
regional under-sampling. Patients
are said to be medically intractable
when seizures remain uncontrolled
despite an adequate trial with two
of the first-line antiepileptics. This
group consists of 0.1 to 0.5 % of the
general population2. Usually, refractory epilepsy is focal in origin, and
mostly involve the temporal lobe. In
fact, 50% of patients with TLE cannot be controlled completely with
medication. Introduction of new
imaging technologies like PET,
SPECT and MRI in clinical practice
Dept. of Nuclear Medicine & PET CT, AIMS,
Kochi, Kerala.
8
has greatly reduced the need for
invasive monitoring. They also
help to avoid associated postoperative complications like hemorrhage and infection. Brain MRI
demonstrates morphologic changes
in approximately 80% of patients
with epilepsy. However, structural
lesions may not always correlate
with clinical, EEG and pathologic
localization of epileptogenic foci.
Therefore, functional information
provides a better road map to delineate the extent of epileptogenic
zone.
SPECT provides information on
neuronal uptake while PET displays
the cerebral metabolism. Seizures
are associated with pronounced
changes in regional cerebral blood
flow. SPECT imaging unfolds significant hyperperfusion at the site
corresponding to ictal focus as
there occurs a 300 percent increase
in cerebral blood flow during an
ictal episode. An interictal study
should show a hypoperfusion on
SPECT or a hypometabolism on PET
in the epileptogenic zone (Fig 1). So
the real power of SPECT lies in the
opportunity of ictal examinations,
with a sensitivity ranging from 90 to
97%. However, as interictal SPECT
has shown low sensitivity (43% to
44%)2 nowadays it is largely replaced with 18F-FDG (18 Fluorine labeled Flurodeoxyglucose) PET. These
images have higher spatial resolution (sharper images) and provide
a direct measure of regional glucose
metabolism. FDG PET ictal study
cannot be performed as FDG injection has to be given within 30 sec
of an ictal episode (FDG half life is
110 min) and the uptake of FDG into
the cerebral tissue post injection is
variable and occurs over a period of
time which may not represent the
actual site of ictal focus. FDG PET is
typically positive in patients with
hippocampal sclerosis on MRI. It
also reveals hypometabolism in a
majority of patients with nonlesional
temporal lobe epilepsy, even in the
absence of hippocampal atrophy.
The most common pathologic
finding in patients with partial seizures is mesial temporal sclerosis
which is thought to represent a gliotic scar3. Excision of this focus can
lead to elimination of the seizures or
significantly improved pharmacologic control in 80% of patients.
CT and MRI have low sensitivity for
seizure foci detection, 17% and
34% respectively4.
99m
Tc ECD cerebral ictal SPECT transaxial images - Show Hyperfusion in Rt temporal lobe (arrow)
FDG interictal PET - Hypometabolism in Rt temporal lobe
corresponding to ictal site.(arrow)
99m
Fig 1 : Tc ECD cerebral ictal SPECT interictal FDG PET (transaxial)
images in a classical case of Right Temporal lobe epilepsy.
CEREBRAL PERFUSION SPECT IMAGING
Most common cerebral perfusion agent used is 99mTc
ECD(99mTechnetium N, N’-1,2-ethylenediylbis-L-cysteine diethylester), marketed as Neurolite. It is a lipophilic agent that crosses the intact blood-brain barrier
with a rapid first-pass uptake. Once in the brain, it is
metabolized into a polar complex that gets retained
within the brain. The brain uptake of the Neurolite is
proportional to the cerebral blood flow (CBF) at the time
of the injection of the tracer3. 99mTc labeled Hexamethyl
Propyleneamine oxime (HMPAO) is another lipophilic
compound similar to ECD but more expensive in Indian
setting and serves as a good alternate for cerebral
perfusion imaging. Patients are prepared prior to the
study. Euglycemic state of patient is essential at the time
of FDG injection. So patients are advised over night
fasting. An indwelling intravenous cannula is secured
and patients are injected in a dimly lit quiet room with
their eyes open. This is done to avoid hyperperfusion to
unwarranted areas in brain which may be stimulated by
pain, noise and light stimuli.
After intravenous injection of HMPAO, it distributes in
brain substantially on first pass. Once inside the neuron,
it is converted into a hydrophilic compound, which is
trapped inside the cell membrane. Therefore, the
distribution of the compound and radiotracer remains
stable for many hours after injection. Effectively, this
means that an image acquisition carried out at some
time after the injection will show the pattern of
perfusion that existed at the time of the injection. All that
requires to be done at the time of the seizure is to give
the injection within 30 seconds of an ictal episode (as
patient will be under video EEG coverage). The acquisition can then wait until the patient has recovered and
imaging can be performed after stabilization of patient.
The mechanism of uptake using both HMPAO or ECD
tracers are similar; subtle variations exist as far as brain
uptake and stability of compound are concerned.
In pre PET era, the interictal ECD imaging was followed by an ictal ECD SPECT. Usually, the interictal scan
is done first. While the patient is on antiepileptics which
is then followed by tapering of antiepileptic drugs to
elicit seizure. And once patient has documented
epilepsy by continuous video EEG monitoring, the
tracer would be injected within 30 seconds of a
documented seizure episode. Timing of the injection is
very crucial as it reflects the cerebral activity at the time
of injection. In a patient with temporal lobe epilepsy
during the seizure, the ictal focus will show
hyperperfusion. This hyperperfusion persists until the
siezure discharge stops, and probably for a short time
after, if the discharge is of short duration. If timing of
injection is delayed and given at the early postictal
phase, the hyperperfused ictal zone loses its intensity
and may become variable.
As the postictal phase progresses, the perfusion drops,
and the zone becomes hypoperfused. This gradually
recovers back to baseline, over a period that may be as
long as several hours but is more typically for several
minutes.If the seizure discharge is prolonged, the change from the ictal to the postictal pattern takes place before the termination of the ictal discharge, probably
around 90 seconds from seizure onset.
While ictal SPECT has high sensitivity and specificity
in temporal lobe seizures, both parameters diminish
with time into the postictal period. Hence for a successful identification of an ictal focus, timing of
9
SPECT & PET Imaging In Epilepsy – An Overview
injection is very crucial and video EEG should to
document that these patients are not under subclinical
phases of seizure.
SPECT images are no matter 60 min post injection or
whenever patient gets stabilized in their next 3 hours.
Images are acquired using a variable angle dual or
triple head Gamma Camera with ultra high resolution/
fan beam collimators. Image reconstruction is done to
obtain Transaxial, Sagittal and coronal slices. SPECT/
PET images can be coregistrated with MRI using a
vendor provided fusion software. Both ictal and
interictal scans are essencially compared to localise the
ictal focus accurately.
FINDINGS
SPECT /PET scans are helpful in patients with normal
MRI or in patients with abnormal MRI findings and a
nonlocalizing EEG5. Since seizures are associated with
increased glucose metabolism (meta-bolism is closely
coupled to cerebral blood flow), ictal SPECT scans show
increased perfusion in the region of seizure onset.
However, obtaining a true ictal injection is important as
has been mentioned earlier, particularly for extratemporal lobe seizures, since with late injections, the
areas of increased perfusion may represent seizure
spread rather than seizure onset.
In patients with temporal lobe epilepsy, during ictal
phase thus is increased perfusion in both the medial and
the lateral temporal lobes. While in the immediate
postictal period (60 seconds), hyperperfusion of the
medial temporal lobe with hypoperfusion of the lateral
temporal lobe are noted. When injected is the late
postictal period (up to 20 minutes postictally), perfusion
in both the medial and lateral temporal lobes may be
decreased3, 6.
Ictal SPECT is not helpful in localizing seizures in
patients with bilaterally independent temporal lobe
seizures, since the procedure samples only one seizure
at a time. Moreover, false lateralization with ictal SPECT
may occur if the seizure ceases in the temporal lobe of
origin while continuing in the contralateral temporal
lobe at the time of tracer injection. For extratemporal
lobe seizure, such as frontal and parietal lobe seizures,
ictal SPECT has sensitivity as high as 90% in localizing
seizures if ictal injection occurs shortly after ictal onset
(i.e, within 20 seconds).
PET scans use18F tracers tagged to FDG (Fluoro deoxyglucose) or 13N ammonia for imaging the brain. It is
useful for demonstrating hypoperfusion and hypometabolism involving the temporal lobe, which
contains the seizure focus. While the degree of hypometabolism can vary greatly from person to person, the
condition is present in the affected lobe in more than
80% of patients with refractory TLE7. A 10% or greater
relative reduction in metabolism in the left temporal
lobe on preoperative FDG-PET is associated with a
lower risk of postsurgical, verbal memory impairment.
In addition, for TLE patients with normal MR results,
PET scans will reveal temporal lobe hypometabolism in
60% of the cases.
10
DISCUSSION
Surgically correctable epilepsies4 are temporal and
extratemporal but with localized focus.
Temporal lobe epilepsy
The syndrome of medial TLE is associated with
hippocampal sclerosis. Approximately 40-67% of these
patients have a history of a complicated febrile
convulsion (a febrile seizure lasting >30 min). These
patients typically present with seizures in late childhood, at which time seizures are well controlled with
drugs. As the child enters adolescence and early
adulthood, the seizures recur and become refractory to
multiple medication trials.
Extratemporal lobe epilepsy
Extratemporal lobe epilepsy also may be treated
effectively with epilepsy surgery, particularly when a
clearly defined lesion is present on high-resolution MRI.
In fact, surgical outcome improves from 20% seizure
free in patients without a lesion to 70% seizure free in
patients with a lesion. Extratemporal seizures may have
variable seizure semiologies that represent seizure
propagation patterns rather than the region of onset;
however, these regions usually have selected pathways
of propagation that may help to narrowly define the
potential epileptogenic region.
Nuclear medicine techniques help by demonstrating
good correlation of the regional cerebral blood flow
exemblified by the uptake of HMPAO and ECD / FDG
PET tracers.
Quantitation software, like SISCOM i.e Subtraction
ictal SPECT co-registered to MRI8,9 increase the sensitivity and specificity of ictal SPECT significantly. In this,
the ictal and interictal images are subtracted and the
subtracted image which actually highlights the ictal
focus site is then superimposed on high resolution MRI.
Surgical outcomes in patients whose seizure focus is
localized with this quantitative technique are well
established. The other method that has been tried as a
localization tool for identifying epileptogenic focus is
using postictal subtraction SPECT co-registered to MRI.
Surgical management is based on anatomical and
functional imaging modalities. Anterior temporal lobectomy provides seizure freedom in 70% or more of
patients with intractable TLE9 Resection elsewhere in
the brain is less successful and more risky while
resection of the extratemporal foci, renders only 4050% of patients free of seizures10.
Advances in neurosciences are foreseen with the
availability of 11C Flumazenil PET (Carbon labeled FMZ
positron emission tomography) to study the status in
epilepsy benzodiazepine receptor. Unlike the
hypometabolic changes seen on FDG-PET studies,
FMZ-PET reveals reduced tracer binding in the mesial
temporal lobe, which may make it a more sensitive test
for patients with TLE arising from the amygdala/
hippocampal regions.
CONCLUSION
In TLE, ictal SPECT has 90% sensitivity in localizing
seizures, with good inter-observer reliability. In medial
temporal lobe epilepsy, the reported sensitivity of 18FFDG PET for localizing the seizure focus is 85%–90%,
with false lateralization being extremely rare. Thus an
ictal SPECT intelictal FDG can accurately localise an
ictal focus.
There are studies on PET/SPECT procedures in
ascertaining the usefulness in frontal lobe epilepsies
and neocortical seizures also.
References
4. Patrella at al : Neuroimaging and early diagnosis of Alzheimer
disease: a look to the future. Radiology 2003. 226: 315-36.
5. Williamson PD, French JA, Thadani VM: Characteristics of medial
temporal lobe epilepsy: II. Interictal and ictal scalp electroencephalography, neuropsychological testing, neuroimaging, surgical results, and pathology. Ann Neurol 1993; 34(6): 781-7.
6. Newton MR, Berkovic SF, Austin MC: Postictal switch in blood flow
distribution temporal lobe seizures. J Neurol Neurosurg Psychiatry
1992; 55(10): 891-4.
7. Drzezga et al :18F-FDG PET studies in patients with extratemporal
and temporal epilepsy: evaluation of an observer-independent
analysis.J. Nucl. Med. 1999 40: 737-46.
1. Kwan P, Brodie MJ: Early identification of refractory epilepsy. N
Engl J Med 2000 . 3; 342(5): 314-9.
8. Petra J. Lewis, Alan Siegel et al :Does Performing Image Registration and Subtraction in Ictal Brain SPECT Help Localize
Neocortical Seizures? J. Nucl. Med. 2000. 41: 1619-26.
2. S. Lavy, E. Melamed, Z. Portnoy,et al., “Interictal regional cerebral
blood flow in patients with partial seizures,” Neurology, 1976; 26,
418–22.
9. Boussion, Houzardi et al :Automated Detection of Local Normalization Areas for Ictal-Interictal Subtraction Brain SPECT.J.
Nucl. Med. 2002; 43(11): 1419 - 25.
3. Saha GB, Maclntyre WJ and Go RT. Seminars in Nuclear Medicine
1994; XXIV(4):324-49.
10. Engel J Jr: Surgery for seizures. N Engl J Med 1996 Mar 7; 334(10):
647-52.
11
Vol. 11, NO: 2
July - Dec 2015, Page 1 - 44
ORIGINAL ARTICLE
A Prospective Study to Determine the Efficacy of CIMT in
Infants with Erb's Palsy
*Ravi Sankaran, *Surendran.K, **K.R Sundaram, *Priyavadhana.R
ABSTRACT
Objective: To test the efficacy of Constraint Induced Movement Therapy (CIMT) in patients with Erb's Palsy.
Method: In this study we followed the effects of mCIMT(modified CIMT) on infants up to their first year. We measured active Range
of motion in the affected limb and Compound Motor Action Potentials, to see if there is a difference in the rate of recovery/
improvement in these parameters.
Result: We found that patients who received mCIMT improved faster than the group that did not both in clinical parameters and
electrophysiological parameters.
Conclusion: mCIMT may be of benefit in helping infants with Erb's palsy recover faster.
Key words: OBPI, Erb's palsy, CIMT, Botulinum toxin, LMN lesion.
INTRODUCTION
Obstetric lesions of the brachial
plexus are not uncommon. The
effects range from temporary functional impairment to a lifelong total
paralysis of one arm. Though this
has been studied in depth by many
clinicians over time acceptable
comprehensive treatment plans
have not emerged. Some prefer
early surgical intervention whereas
others are more conservative and
reserve surgery for infants in whom
spontaneous repair is deemed insufficient after a certain period.
Unfortunately that certain period is
not fully agreed upon either.
Part of this uncertainty is due to a
lack of appropriately designed outcome studies. Another major difficulty is the lack of reliable indicators
of prognosis. Nerve Conduction
Studies (NCS) would seem an ideal
tool for this purpose, but it has been
seen that even with normal NCS
deformities and impaired function
exist.
With respect to non-surgical
interventions the treatment plan is
even less clear. The majority of clinicians will refer the patient to Physical Therapy, but what is done from
there is highly variable. Some therapists promote only passive range of
motion, whereas others may suppleDept. of *Physical Medicine and Rehabilitation,
**Neurology, AIMS, Kochi.
12
ment the same with electric stimulation. As the majority of therapies
are not directly aimed at functional
goals this results in developmental
disuse. Attempts to make the developing brain aware of the affected
limb, and its potential is critical to
good outcomes.
Taub introduced the therapeutic
intervention called Constraint Induced Movement Therapy (CIMT)
which was later applied to children
with cerebral palsy. Significant improvements have been seen when
used in patients with Upper Motor
Neuron problems. While it can be
argued that the prior patients have a
relatively intact peripheral nervous
system, and brachial plexus injury
infants do not we felt it warranted
testing.
bined with Constraint Induced Movement Therapy(CIMT) a pilot study
was done to calculate sample size.
Based on the results using 99%
Confidence Intervals and 90%
Power a sample size of less than 10
was calculated for each group.
Total no. of Infants: 52
Group A- (HEP +/- Botulinum toxin) - 30
Group B-(HEP with mCIMT+/- Botulinum
toxin) - 22
Study Period: 18 months
Study Setting: Amrita Insitute of
Medical Sciences.
Patient selection criteria
Definition of OBPI
Trauma to the Brachial plexus in the
perinatal period as per the Louisiana
State University (LSU) classification
of OBPI.
In this study we follow the effects
of mCIMT(modified CIMT) on infants up to their first year. We will
measure active Range of motion in
the affected limb and Compound
Motor Action Potentials, and see if
there is a difference in the rate of
recovery/improvement in these
parameters.
Erb's Palsy- C5, 6, root with or without upper trunk involvement.
Erb's Plus- same with C7 root involvement.
Klumpke- C8, T1 root with or without Lower trunk involvement.
Erb- Klumpke- all involved.
MATERIALS AND METHODS
Study Design: Prospective Study.
Sample size: Since no prior study
has been done comparing the effects of Home Exercise Program
(HEP) with Home exercise com-
Inclusion criteria
Patients with unilateral Erb's
palsy.
Palsy per the Lousiana State University Classification.
Infants up to 2 months age.
Exclusion criteria
Other Neurological disorders in the perinatal period.
Birth related and subsequent bony trauma to infant
skeletal system.
Bilateral Obstetric Brachial Plexus Injury.
Traumatic Brachial Plexus Injury.
Malnutrition.
Con-commitant UMN injury.
Parents not willing for study,follow up or not giving
written consent.
MEASURES
1. Electrodiagnostic variable NCS/ EMG machine.
Axonal Viability index. This is a measure used to
determine the rate of recovery in injured nerves by
comparing the Compound Motor Action Potential
(CMAP) amplitude of the affected side to that of the
normal side. The patient must have only one limb
affected. This is used in children as acceptable range for
CMAP amplitude varies. After obtaining bilateral
CMAPs we divide the CMAP of the affected side by that
of the normal side. This gives the value in percentage.
AVI = CMAP abnormal limb/ CMAP normal limb.
Nerves for comparison
Axillary Nerve studied on Deltoid
Musculocutaneous studied on Biceps
Suprascapular studied on Infraspinatus
2. Qualitiative Upper Extremity Skills Test (QUEST
Score)
The QUEST score (Qualitative Upper Extremity Skills
Test) is a scale validated for neurological conditions in
children. Considering that our patients do not have
proper proximal power it was not possible to scale them
using all the measurements this includes. We focused
on using the Dissociative Movements sub-scale only.
The value it provides is a total for the limb and is a single
composite value. This made it easier to monitor the
progress patients were making.
3. Goniometric measurement of Range of Motion
4. Botlinum toxin
Botulinum toxin is injected into the co-contracting
muscle groups to prevent contracture. Co-contracting
muscles are antagonist muscle groups that contract when
the agonist attempts to contract. It is found by palpating
both groups simultaneously as we monitor for the agonist
activity. For example, if we are checking for Triceps cocontraction, during elbow flexion by biceps we monitor
Triceps activity also. Normally contraction would not be
expected in Triceps, but it will get tensed if it is cocontracting. This increases the chance of contracture
formation. There are a few expected co-contracting
muscle group patterns that are looked for in OBPI.
Triceps with Biceps induced elbow flexion
Lattisimus and Pectoralis Major with Deltoid/Supraspinatus induced shoulder abduction.
The patients in this study were assessed for cocontracting muscles at every appointment. This was
found in the 6th month usually and the overactive
muscles were injected. As they were all nearly the same
weight the same number of units were administered to
them. Then they were instructed to continue along their
treatment plan.
5. Arm gator
This was used as a constraint in the study. This is a soft
lined leather sheet that can be rolled into a cylinder and
can be closed with 3 velcro straps. A fourth strap would
encircle the waist and keep the limb fixed to the trunk.
Fig 1: Arm gator
METHODOLOGY
All infants satisfying the inclusion and exclusion
criteria were included in the study after getting written
informed consent from their parents. Each infant then
underwent a baseline Electrodiagnostic study and
Axonal Viability Index (AVI) was assessed. A baseline
Dissociated movements Subscore of QUEST was also
done. The parents were then given training on Home
Exercise Program at entry.
Home Exercise Program (HEP). This consists of a
simple program that the parents can carry out on the
child. The exercises stretch the affected arm in the
shoulder abduction and external rotation, elbow
flexion, forearm supination, with wrist and finger
extension.
At 3 months of age, the infants were reassesed again.
QUEST score was done. Degree of contractures was
then assessed. Contractures in shoulder adduction,
internal rotation, elbow extension, forearm pronation,
and wrist flexion were noted and scaled accordingly:
0= no contracture
1= < 25% contracture
2= 26 - 50% contracture
3= 51 - 75% contracture
4= 76 - 100% contracture
Matching was done for children who showed
development of co-contraction. These subsets were
given additional treatment with Botulinum toxin for the
co-contracting muscle.
They were separated into groups as follows:
Group A– HEP with or without Botulinum toxin
Group B– HEP and CIMT with or without Botulinum toxin
Group A was taken as the control group and Group B
was taken as the Study group.
13
A Prospective Study to Determine the Efficacy of CIMT in Infants with Erb's Palsy
Constraint Induced Movement Therapy
The protocol was as follows:
Introduction of CIMT at age 3 months to those in the
appropriate groups. CIMT was given in addition to the
ongoing HEP. Parents were given the arm gator and told
to apply it for 5 minutes daily for the first 2 days and in
that time keep the infant engaged in play. At the start,
the parents were expected to show colorful and noisemaking toys to distract the infant. On the third day they
were to increase it to 5 minutes twice daily, then thrice
daily by day 5. By the begining of the next week they
had to make the first session 10 minutes and the
reminder 5, and then by day ten make it 10 minutes
twice daily. By day 13, they would be doing 10 minutes
thrice daily. Thus on a weekly basis they would increase
the duration up to a maximum of 1 hour thrice daily
with play. In that interval the infant would be expected
to be developing reaching and start grasping such that
the CIMT would be ensuring they use the affected limb
daily. By 4 months, the parents were educated on how
to produce voluntary movements to strengthen selected
muscle groups. As the child would already be reaching
by this point of time the parents were told to keep the
toys near the head on the affected side inducing
shoulder abduction, then to keep it alongside the trunk
at arm level to induce external rotation, and just above
the arm to induce elbow flexion. At 6 months follow-up,
the child would be manipulating objects to some
degree and the parents were told to offer things to the
child so as to keep the forearm in supination. Aside from
teaching the parents, live videos of the sessions were
made on their mobile phones for their reference. They
were asked to make a video of their therapeutic play
sessions at home for follow-up. The control group was
managed in the same way with the exception of not
following the CIMT protocol. The infants were then
assessed periodically at ages 6 months and 12 months
with QUEST scores and AVI. Any contractures present
were also noted.
STATISTICAL ANALYSIS
The data collected was entered in MS excel and then
analysed using SPSS software. The statisitical significance of the differences in mean change of parameters
between the different treatment groups was done using
One way Non-parametric Analysis of Variance. We had
planned for Parametric studies, but due to attrition from
non-compliance with CIMT we had to option for NonParametric studies. Significance of pairs of the groups
was identified by multiple comparison test. Statistical
significance of the mean change in study parameters
after treatment in different groups was tested by
applying Wilcoxon's signed rank test.
OBSERVATIONS
The study consisted of total of 52 infants with OBPI,
of which 30 were included in Group 1 (Controls) and 22
in Group 2 (CIMT group). 8 patients from the CIMT
group failed to comply nwith protocols and were exclu14
ded prior to statistical testing. Out of the total 52, 29
were males and 23 females. The present study showed a
slighly more prevalence in males which is slightly
contrary to the literature which suggests a prevalence of
OBPI in female gender. Most of the infants were recruited into the study in first month of age (group A 70%,
group B 86%). Right sided brachial plexus injury was
more compared to left (group A 70%, group B 68%).
The test group had more apparent Pre-ganglionic
lesions at baseline (group A 56%, group B 90%).
Though the difference was significant we ignored the
baseline data as studies in this age may not be reliable.
The majority of patients who needed Bo-Tox were in
group A (group A 47%, group B 32%). Though there was
a difference between the groups it was not significant
(p-value 0.077). A statistically significant difference was
found in this at 12 months. With respect to the QUEST
score there was a significant difference between the
groups at 6 and 12 months. For the AVI-MCN a statistically significant difference were found between the
2 groups at 12 months. At the start the test group had
slightly worse scores, but began improving faster by
6 months. The test group had an overall better outcome.
For the AVI-MCN the mean change was significant. For
the Axillary AVI the difference was significant at 12
months. The Mean change was also significant. For the
SSN AVI the difference was significant at 12 months,
and with the mean change at that time. (Ref table 1 for all
p values).
Table 1: Primary variables
Variable
QUEST
0 months
3 months
6 months
12 months
MCN
0 months
6 months
12 months
Axillary
0 months
6 months
12 months
SSN
0 months
6 months
12 months
Group 1
(30)
0.75±0
0.7883±
0.02437
0.8403±
0.0452
0.906±
0.0662
0.3613±
0.2839
0.6610±
0.2162
0.9713±
0.0658
0.4010±
0.3417
0.7067±
0.2481
0.9530±
0.1001
0.4577±
0.3025
0.6907±
0.2283
0.9750±
0.0383
Group 2
(22)
0.75±0
0.7736±
0.0173
0.8786±
0.0375
0.963±
0.0196
0.2073±
0.2292
0.5864±
0.2250
1.00±0
p value
0.2877±
0.2526
0.6559±
0.1603
0.9991±
0.0029
0.2759±
0.2111
0.6991±
0.1423
1.0 ± 0
0.307
1
0.24
0.002
0.003
0.02
0.349
<0.001
0.262
<0.001
0.38
0.993
0.002
Shoulder adduction contractures were present in both
groups more in group 1 than group 2 at 3 months of age
but this was not statistically significant. After the
initiation of CIMT, shoulder adduction contractures
were significantly less in the CIMT group (Group B) at
both 6 months and 12 months. Shoulder internal
rotation contractures were present in both groups more
the group 1 than 2 from the start and throughout. A statistically significant difference was found in this at 6
months in favor of the CIMT group. Forearm pronation
contractures were present in both groups more in group
1 than 2 from the start.
RESULTS
Overall a trend towards faster improvement was
noted in group B once the CIMT was added. This was
seen in QUEST scores and the AVI for all 3 nerves at 12
months. Though many other NCS values were significant in favor of the same group they were not given
value as the baseline NCS data was not taken as reliable
at that age.
DISCUSSION
When a nerve is injured the fibers degenerate.
Regeneration occurs at the nerve cell body, the proximal stump, the distal stump and the end organ1. While
PNS repairs itself after injury the CNS uses plasticity to
compensate for the loss2. The success of nerve regeneration depends on the distance from the injury site. Even
when good motor recovery occurs deficits in proprioception may impair functional outcome3. Reinnervation
must occur within approximately 12–18 months to
provide a functional outcome. If the muscle is not
reinnervated, fibrosis gradually progresses and will
replace the muscle completely within about 2 years4.
With respect to neuroplasticity, thinking, learning,
and acting actually change both the brain structure and
organization5. Adjacent areas in the sensory cortex (the
arm and face) will substitute for the area whose function
is lost6.
Obstetric plexopathy has a mean incidence of 0.38
to 3 per 1000 live births in industrialized countries7.
Vertex presentation with shoulder dystocia (often secondary to maternal Diabetes Mellitus) is a common cause.
Other related factors may be method of delivery, multiparity, and ethnic background8.
Electrophysiology studies are usually done at 3
months as this is when surgery is decided on. Interestingly sometimes EMG may contradict the NCS findings9.
In patients with paralysis Motor Unit Potentials (MUP)
may be present, and denervation activity may be
absent10-13.
Paradiso et al. described 100 EMG studies in 78
children with obstetric plexopathy of Erb's type, aged
between 5 days and 15 months. Denervation was seen
from day 10 through to week 19. Abnormal MUPs was
seen week 13 onwards14.
The Axonal Viability Index (AVI) is defined as the
amplitude of the affected side expressed as a percentage
of the corresponding value of the healthy side. Also it is
seen that the ratio between the amplitude of the compound muscle action potential of the affected side and
that of the healthy side is related to clinical recovery15.
Some patients present with weakness despite NCS
normalization. This may be due to either developmental
disuse, or co-contraction. Developmental disuse is a
CNS problem due to poor sensory-motor stimulation of
the brain during maturation. In aberrant reinnervation
due to abnormal motor branching, one motor neuron is
responsible for innervation of muscles with antagonist
function. The mechanisms involved in co-contractions
are probably not mutually excluding16.
While changes happen in the PNS during recovery,
there are also changes in the CNS simultaneously. The
developing brain has never made an effort to include
the affected limb in the developing stages of 'executive
function'. In an infant these functions are as basic as
reaching and grasp but they are critical to use of the limb
later. As the limb is not used in such a fashion developmental disuse/learned non-use develops. The cortical centers for producing these effects may not mature.
Though 80-90% of patients with OBPI have a favorable prognosis, this does not directly translate into
normal function for the involved limb though. There are
three reasons for this: The first reason is assessing the
functional end stage. The second is due to immature
motor control. Lastly, co-contraction has been shown to
affect the functional end stage.
Co-contraction refers to activation of antagonistic
muscles or muscles not normally involved in the
intended movement, along with contraction of an
agonist. Recurring patterns of cocontraction in obstetric
plexopathy include: activation of the triceps when
elbow flexion is intended; activation of shoulder
adductors when abduction is intended. Recent therapeutic interventions aim to abolish this counterproductive effect of nerve regeneration with botulinum
toxin or muscle transposition17. All these factors suggest
that a functional end stage in obstetric plexopathy can
only be assessed reliably in children of about 4 years or
older.
Constraint-Induced Movement Therapy (CIMT) aims
to reverse the behavioral suppression of movement in
the affected upper limb by constraining the use of
nonaffected limb and providing massed practice of
activities with the affected limb with specific functional
goals as outcomes18. The concept of constraining the
normal limb to improve the activities of the affected
upper limb was first put forward by Taub. Very few
studies have been done with CIMT in Obstetric Brachial
Plexus palsies19. Promoting early use can enhance
motor development20.
Taub required the children to don the restraint for 24
hours per day. Despite the emerging popularity of
CIMT, a review identified a significant treatment effect
in only a single trial which adopted a less intensive
modified form of CIMT21. The modified CIMT (mCIMT)
involved the application of a restraint on the unaffected
upper limb and less than three hours per day of therapy
provided to the affected limb22. While a positive trend
was found favoring CIMT no significant treatment effect
was demonstrated for these interventions when compared with traditional services23.
15
A Prospective Study to Determine the Efficacy of CIMT in Infants with Erb's Palsy
Concerns have been mentioned with respect to CIMT
in younger children (0–18 months) with hemiplegia.
There are relatively few accounts of adverse events that
have been reported in pediatric CIMT literature that
support these concerns24. The mCIMT protocol incorporates the two fundamental components of CIMT as
described by Taub et al; the use of a restraint device and
the provision of massed practice but limited to 3 hours
of therapy25.
CIMT effects change by making a situation where the
patient receives positive reinforcement for use of the
weaker arm, and negative reinforcement for efforts to
use the constrained stronger arm26. At the same time, it
increases use of the more impaired arm and induces
cortical reorganization27,28. Slowly the patient reaches a
''critical mass'' of intensity and the impaired limb will
regain cortical space to maintain its use29,30. Sunderland
and Tuke label this as “compensatory learning31.”
A pilot study of CIMT on two children with OBPI has
shown a certain degree of improvements for both
patients. A functional improvement observed by the
parents and the participant was reported, which was in
accordance to improvements of motor functions
observed in neurological assessment32.
Overall the test group was worse than the control
group at baseline for the primary NCS variables. The test
group showed rapid improvement once the intervention was added. The recovery speed increase was
evident in the QUEST score, Musculocutaneous, Axillary, and Suprascapular nerve AVIs at 12 months. Contractures were noted as more promininent in the control
group and overall this did not improve as well compared to the test group. There were statistically significant difference noted for: Shoulder Adduction contractures at 6 and 12 months, Shoulder Internal Rotation
contractures at 6 months, and Forearm pronation contractures at 12 months.
With the addition of mCIMT the baby was more
likely to move the affected limb more frequently. Once
mCIMT was started volitional tendency to use the limb
would start earlier. This likely prevented developmental disuse from occurring, compared to the control
group which only got passive stretching.
The 2 groups were not comparable at baseline for
the AVI. This is explainable in that NCS at that time is
not accurate. Regardless the QUEST score was comparable hence overall the groups were similar.
Many parents were concerned that constraint
would damage the normal limb. Despite allaying their
fears we still had 8 patients fail to comply with the
treatment protocol. Follow-up was done per protocol
using home recordings of therapy sessions made in
smarthphones, as many of the children who came were
uncooperative on arrival.
CONCLUSION
mCIMT added to the rehabilitation plan allows for:
More recovery of volitional motor activity in the
16
affected limb.
better electrophysiological recovery in Musculocutaneous, Axillary, and Suprascapular nerves.
less contractures.
Considering the data gathered we can conclude that
those patients who did not receive mCIMT:
did not improve as well as those who did.
had more co-contracting muscles that required Botox
injections.
despite Botox still did not improve as well overall as
the group with mCIMT.
We cannot clearly say if Bo-Tox had a role in the
outcomes we found.
This study is unique as no other study has looked this in
depth into the conservative treatment of Erb's palsy
using a multi-modal approach.
Limitations:
High attrition rate
Due to attrition we had to use non-parametric studies
for statistics
Inability to intensely monitor therapy
No control on stimulating devices used by parents
References
1. Burnett MG, Pathophysiology of peripheral nerve injury: a brief
review. Neurosurg Focus 2004; 16:1–7.
2. Burnett MG, Pathophysiology of peripheral nerve injury: a brief
review. Neurosurg Focus 2004; 16:1–7.
3. Pollock M, Nerve regeneration. Curr Opin Neurol 1995;8:354–8,
Thomas P.K., Peripheral neuropathy. 3rd ed. Philadelphia: W.B.
Saunders; 1993. p. 990.
4. Sumner AJ, Aberrant reinnervation. Muscle Nerve 1990; 13:801–3.
5. Konorski J, Conditioned reflexes and neuron organization Cambridge University Press;1948. page 89.
6. Ramachandran VS, Can mirrors alleviate visual hemineglect ?
Medical Hypotheses 1999;52:303-5.
7. Adler JB, Patterson RL Jr. Erb's palsy: long-term results of treatment
in eighty-eight cases. J Bone Joint Surg Am 1967;49:1052-6.
8. Gilbert A, Obstetrical brachial plexus lesions. J Hand Surg Br. 1991
Dec;16(5):489-91.
9. Van Dijk JG, Why is the EMG in obstetric brachial plexus lesions
overly optimistic? Muscle Nerve 1998;21:260–1.
10. Vredeveld JW, The electromyogram in obstetric brachial palsy is
too optimistic: fiber size or another explanation? Muscle Nerve
1999;22:427–8.
11. Zalis OS, Motor patterning following transitory sensory-motor
deprivations. Arch Neurol 1965;13:487–94.
12. Salafsky B, Development of fibrillation potentials in denervated
fast and slow skeletal muscle. Am J Physiol 1968;215:637–43.
13. Arancio O, Fibrillatory activity and other membrane changes in
partially denervated muscles. Muscle Nerve 1989;12:149–53.
14. Paradiso G, Prenatal brachial plexus paralysis. Neurology 1997;
49:261–2.
15. CO Heise, Motor Nerve-Conduction Studies in Obstetric Brachial
Plexopathy for a Selection of Patients with a Poor Outcome.J Bone
Joint Surg Am. 2009 Jul;91(7):1729-37.
16. Heise CO, LR Gonçalves, ER Barbosa, et al, Botulinum toxin for
treatment of cocontractions related to obstetrical brachial plexopathy
Arq Neuropsiquiatr 2005;63(3-A):588-91.
17. Hoare BJ,. Modified constraint-induced movement therapy or
bimanual occupational therapy following injection of Botulinum
toxin-A to improve bimanual performance in young children with
hemiplegic cerebral palsy: a randomised controlled trial BMC
Neurology 2010, 10:58.
18. Sunderland A, Neuroplasticity, learning and recovery after stroke:
a critical evaluation of constraint-induced therapy. Neuropsychol
Rehabil. 2005;15:81–98. Copyright 2005, Psychology Press.
19. Glover JE, 2002. The effectiveness of constraint induced movement therapy in two young children with hemiplegia. Ped Rehab
5:125-31.
20. Taub E. Somatosensory deafferentation research with monkeys:
implications for rehabilitation medicine. Neuroscience Letters Vol
250, Issue 1, 26 June 1998, Pg 5–8.
magnetic stimulation support hypothesis of coexisting central
mechanism in obstetric brachial palsy. J Clin Neurophysiol (2007).
24, 48-51.
26. Sutcliffe TL, Cortical reorganization after modified constraintinduced movement therapy in pediatric hemiplegic cerebral palsy. J
Child Neurol (2007 22, 1281-7).
27. Wolf S, Elements of training revisiting constraint-induced
movement therapy: are we too smitten with the mitten: is all nonuse
learned and other quandaries. Physical Therapy September 2007 vol.
87 no. 9, 1212-23.
21. Behavioral Psychology in Rehabilitation medicine: Clinical Applications. Williams and Wilkens. 371-401.
28. Korak KJ, Tam SL, Gordon T, et al. Aszmann OC Changes in
spinal cord architecture after brachial plexus injury in the newborn.
Brain (2004). 127, 1488-97
22. Taub E. Diminution of early environmental control through
perinatal and prenatal somatosensory deafferentation. Biol Psychiatry
1975. 10: 609-26.
29. Evidence-Based Care Guideline Pediatric Constraint Induced
Movement Therapy (CIMT) Original Publication Date: 02-16-2009
Cincinatti children's hospital.
23. Taub E, Technique to improve chronic motor deficit after stroke.
Arch Phys Med Rehabil 1993. 74: 347-54.
30. Eliasson AC: The Manual Ability Classification System (MACS) for
children with cerebral palsy: scale development and evidence of
validity and reliability. Dev Med Child Neurol, 48(7): 549-54, 2006.
24. Taub E, Crago JE, Burgio LD, et al. An operant approach to
rehabilitation medicine: overcoming learned nonuse by shaping. J
Exp Anal Behav. 1994. 61" 281-93.
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with obstetric brachial plexus palsy; Winterthurerstr. 190 CH-8057
Zurich.
17
Vol. 11, NO: 2
July - Dec 2015, Page 1 - 44
ORIGINAL ARTICLE
Mid-term follow up and Functional outcome after Surgical
fixation of Displaced Acetabular Fractures
– An Institutional experience
Melvin J George, Druvan.S.P, K.K.Chandrababu, V.K.Bhaskaran
ABSTRACT
Incidence of acetabular fractures are on the rise now due to increased high velocity injuries. Management of these complex
fractures needs accurate knowledge of anatomy, approach and the potential complications. We studied patients with displaced
acetabular fractures treated surgically over a period of 10 years with minimum follow up of 3 years to evaluate the functional
outcome. Fractures were classified according to Letournel and Judet classification. Radiographic imaging was done to assess the
reduction and clinical scoring was done with Modified Merle D'Aubigne Score and Harris Hip Score. Out of the 54 patients whom
we identified, 20 turned up for follow up studies. 75 - 82.5% of patients had excellent – good scores. Poor function was obtained in
3 patients. Two of them had rather simple fractures and had achieved perfect anatomical reduction in the follow up radiograph.
Also some patients with comminuted associated fractures have shown excellent scores in spite of near anatomical reduction in
radiographs. This points to the fact that apart from the reduction, severity of articular cartilage injury, labral and soft tissue injuries
also need to be assessed and addressed to obtain optimal functional outcome.
INTRODUCTION
Acetabular fractures usually occur in younger age group due to high
velocity injury. These injuries are
most often associated with other
serious injuries or polytrauma. But
over recent years, the incidence of
acetabular fractures has increased,
especially in elderly population due
to increased longevity of life, as also
an increase in their involvement in
high velocity injuries. If left untreated, displaced acetabular fractures
can lead to early onset osteoarthritis
of the hip. Acetabular fractures are
commonly classified by the “Letournel and Judet” system12. It was in
the late 1960s that Letournel and
Judet proposed the importance of
surgical fixation of acetabular fractures and congruent reduction for
better functional outcome. But, initially, surgical fixation was a challenge to the orthopaedic surgeons
due to difficult exposure, frequent
complications, difficulty in obtaining anatomical reduction and joint
congruency and ultimately poor
functional outcome. The outcome is
potentially dependent on personal
characteristics of the patient and
circumstances of the accident13,
type of fracture, displacement and
comminution as well as concomitant diseases have been said to
affect clinical outcome14. The funDept. of Orthopaedics, AIMS, Kochi.
18
ctional outcome is influenced by
many factors, including fracture
pattern, surgeon's expertise, patient's age, associated chondral damage and neurovascular injury and
patient's co-morbidities and functional expectations. With the advent of CT, expert surgical training
and other intra operative radiographic facilities, and greater functional demands for the patients,
surgical fixation has become the
standard treatment in acetabular
fractures. We present the mid term
follow up and evaluation of functional outcome of 20 patients with
acetabular fractures surgically fixed
in our Institution between 2002 and
2012.
MATERIALS AND METHODS
Aims and Objectives
To evaluate and determine the
functional outcome of patients with
acetabular fractures surgically
treated in our Institute.
Inclusion Criteriae
Those patients admitted with
acetabular fractures and surgically
treated in our Institute between
2002 to 2012 who have given valid
informed consent to take part in the
study.
Exclusion Criteriae
Those patients with open fracture, those lost to follow up and
patients managed non surgically.
We identified 54 patients who
had acetabular fractures and underwent Open Reduction and Internal
Fixation in our Institute during the
period 2002 to 2012. Of these, 20
patients turned up for functional
evaluation and follow up studies.
The relevant clinical and radiological findings, mechanism of injury,
fracture pattern and classification
were noted at the time of admission.
Fracture classification was done
according to Letournel and Judet
Classification. We classified the data
according to sex, age, fracture pattern and the associated complications. Operative indications for
acetabular fractures are unstable or
incongruence of the hip, posterior
wall or anterior wall fractures with
column displacement29.
On admission, all the patients
were evaluated with three radiological views – AP Pelvis and 45*
oblique views of Judet and CT scan.
The indications for surgery were
instability of the hip, displacement
of a fragment by > 2 mm, dislocation with a posterior wall fracture,
and articular impaction or depression as seen on the pre-operative
CT scan. All patients were operated
using single approach (Kocher-Langenbeck, ilioinguinal, or extended
ilioinguinal). Open reduction with
internal fixation was attempted to achieve anatomical
reduction of the articular surface of the acetabulum.
Suction drain was used routinely and was removed after
48 hours. Post-operatively skin traction was applied and
no prophylaxis for heterotopic ossification and DVT was
used in any patient. Immediate post operatively, ankle
mobilization was started.
We retrieved the post operative images (AP Pelvis)
of these patients and evaluated for reduction and
comparison with the latest radiographs. In all cases,
immediate post operative complications were noted.
Mobilisation was done as early as possible with the aid
of physiotherapist. Toe touch weight bearing was
allowed till around 6 weeks, partial weight bearing for
next 6 weeks and full weight bearing from thereafter.
Clinical and radiological assessment was undertaken at
six and 12 weeks, four, six and 12 months post-operatively and annually thereafter. For the purpose of the
study, all these patients were called back for repeat
radiological and clinical evaluation and scoring (Modified Merle D'Aubigne Score and Harris Hip Score).
Heterotopic ossification, Avascular Necrosis and Osteoarthritis were diagnosed based on clinical and X ray
findings.
RESULTS
Altogether we obtained 54 patients who underwent
Acetabulumn ORIF during the study period. One patient
had bilateral acetabuli fracture, one sustained open
fracture injuring the rectum, 24 were lost to follow up
and 8 patients died due to age related poor health.
Overall, we had total cases of 20. Majority of them were
males (78%). Age of the patients ranged from 14 years to
70 years. Mean age was 42.6. The follow up period
ranged from 13 years to 3 years and the mean follow up
period was 7.53 years. Right hip was involved in 15
cases and left hip in 5 cases. Clinically the subjects were
graded according to Modified Merle D'Aubigne Scoring
and Harris hip Scoring as Excellent, Good, Fair, and
Poor.
Table No:1 showing the frequency of each fracture classes in the
study group.
Type
Fig. No: 1, 2 - X ray images showing a posterior wall fracture – AP
view and iliac oblique
Fig. No: 3 - Obturator oblique view.
Fig.No: 4 - CT image of posterior wall fracture
n
Anterior column
1
Both Columns
3
Posterior Column
4
Posterior wall
6
Posterior wall and column
3
Posterio Wall, Transverse
T type
Transverse fracture
1
Total
The most common fracture noticed in our study
group was posterior wall fracture (30%). Our study results with regard to the incidence of fracture types were
comparable with that of Magu NK et al.1 and Letournel
et al2.
1
1
20
Fig. No: 5 - Immediate post op X ray image
19
Mid-term follow up and Functional outcome after Surgical fixation of
Displaced Acetabular Fractures – An Institutional experience
Fig. No: 6 - 3 months post op X ray
Fig. No: 10 - 10 years post operative X ray showing extensive HO
formation and OA changes.
Fig. No: 8, 9 - X ray image of bilateral acetabulumn fracture with
open book injujry to pelvis and post op image after ORIF.
Table No: 2 showing the various complications associated with each
fracture classes.
Complication
Type of fracture
HO
Sciatic
palsy
AVN
Dislocation
OA
Infection
Anterior column
1
0
0
1
2
0
Both Columns
0
2
0
0
1
0
Posterior Column
0
1
1
1
0
0
Posterior wall
0
0
0
2
1
0
Posterior wall
and column
2
0
1
1
2
0
Posterior wall,
Tranverse
0
0
0
0
1
1
T type
0
0
1
0
0
0
Transverse
fracture
0
0
0
0
1
1
Total (20)
3
3
3
5
8
2
The most common complication we encountered
among the patients in our study group was osteoarthritis
(40%). Avascular necrosis occured in 15% of patients.
Most of these patients had a follow up period of more
than 6 years. The incidence may rise with further follow
up period. No specific fracture pattern was found to be
associated with osteoarthritis and avascular necrosis. In
our study group, heterotopic ossification was found in
15%, sciatic nerve palsy in 15% and 5 patients had
dislocated their hip at the time of presentation. 60% of
these patients developed AVN on follow up of at least 4
years. Infection was found in 2 patients (10%) in which
extensile approach was used for fixation. The incidence
of infection in our study is comparable to similar
20
Fig. No: 11,12,13 - Pre op X ray, Post operative X ray image at 5 years
follow up showing OA changes, for which THR was done.
Table No: 3 showing the clinical grades obtained with the two scoring
systems.
MMDA
Score
Harris
Hip Score
Excellent
3
2
Good
14
13
Fair
2
3
Poor
1
2
Clinical
grade
studies15,16. Three patients ( 15%) underwent THR 2,5
and 7 years after the acetabular surgery due to post
traumatic arthritis. The conversion rate to THR is
comparable with similar studies17,18.
85% and 75% of patients made it into the Excellent
– Good group according to the MMDA score and Harris
Hip Score respectively. Fair - Poor function was obtained in 1 patient ( MMDA ) and 2 patients (HHS). Of these,
one patient had an ipsilateral shaft of femur fracture, and
the other had post operative infection requiring surgical
debridement 3 times after the surgery. In the same
group, two patients had perfect anatomical reduction, in
the follow up radiograph. Clinical scoring not comparable with the radiological scoring can be due to
multiple reasons of which the most likely is the severity
of the cartilage, labral or other soft tissue injury at the
time of insult or intra-operative.
Table No: 4 showing the frequency distribution of mechanism of
injury
Mechanism
Frequency
Percent
Bike
9
45.0
Fall
2
10.0
MVA
7
35.5
Pedestrian
injury
Total
2
10.0
20
100.0
As evidenced from the table, the most common
mechanism of injury is bike accident. (45%). The relative number of elderly and younger generation using
bicycles and the increased traffic may be the cause.
DISCUSSION
Fractures of acetabulum and pelvis constitute only
2% of all fractures3,4 but they are associated with significant morbidity and mortality due to associated
injuries5. Several studies report that accurate reduction
and rigid internal fixation can decrease the incidence of
post-traumatic arthritis and improve functional outcome
6-8
. Clinical outcome after acetabular fracture surgery is
difficult to predict. Poor bone stock in older patients,
comminuted articular surface fractures and poly-trauma
patients with multiple co-morbidities are adverse factors
influencing outcome9. Current trends in the treatment of
these fractures include open reduction and internal
fixation10 according to the principles that apply to all
inta-articular injuries. Judet et al. in 1960s classified
these fractures and established the principles of
operative management10. Elementary fractures are
1) Posterior column, 2) Posterior wall 3) Anterior column, 4) Anterior wall and 5) Transverse fracture. Associated fractures are 1) Both columns, 2) T shaped,
3) Transverse + Posterior wall, 4) Anterior column +
posterior hemitransverse and 5) Posterior coulumn +
posterior wall.
and internal fixation of acetabular fractures is to return
the patient to pre fracture level of activities. This goal
can be achieved by properly planned approaches.
However, despite the appearance of an anatomical
reduction on radiographs, there may still be imperfections on areas of the articular surface that are
invisible on standard plain radiographs or are hidden by
plates and screws. In some of our patients with anatomical reduction, functional scoring does not correlate.
It must therefore be concluded that clinical results
depend mostly on the severity of articular cartilage
injury happened at the time of insult and the capability
of the acetabulum in an adult to tolerate changes in the
distribution of pressure and perhaps to reshape itself
over time. Detailed study in this regard using cartilage
mapping or arthroscopic evaluation may be warranted.
The results of our treatment could be improved by
more experience in the surgical group. Complications
can occur from the injury per se or can be the result of
surgical treatment. Early complications include
thrombo-embolism (30% to 50%), neurologic injury
(16 % to 30%), infection (3% to 9%), malreduction, loss
of reduction, intra-articular hardware and vascular
injury. Late complications include avascular necrosis
(2% to 25%) heterotrophic ossification (1% to 60%),
post traumatic arthritis (12% to 57%). Despite perfect
reduction, osteoarthritic changes are expected to
develop in the long term for which most common procedures done are hip arthrodesis or total hip replacement.
CONCLUSION
The acetabular fractures are seen in younger age
group following high velocity injuries. Proper radiological assessment of fracture type is necessary to
decide the proper line of management, which is mandatory for better outcome. The operating surgeon
should have thorough knowledge of this region. An
appropriate pre-operative planning, intra-operative
execution and careful post-operative monitoring help to
get good outcome in this set of fractures. An increase in
the rate of anatomical reduction and decrease in the rate
of operative complications should be the goal of
surgeons who treat these fractures, even though set
backs do occur due to associated injuries and inappropriate rehabilitation.
Incidence of acetabular fracture is on the rise in every
part of the world. Road traffic accidents are the main
cause of these injuries in young adult males between 20
to 40 years of age group. The outcome of open methods
can be improved with more surgical experience in
treating acetabular fractures which will enable us to
minimise the complications with appropriate and
innovative treatment methods. Finally, even if the
prognosis for the restoration of normal joint function is
not good, restoring normal anatomy will enable the
patient to have a better quality of life and makes it easy
for future reconstructive procedures.
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24(5):759-67.
Vol. 11, NO: 2
July - Dec 2015, Page 1 - 44
ORIGINAL ARTICLE
Predicting Clinical Outcome In Acute Ischemic Stroke Based
On TOAST Classification
Ajith Kumar J, *Vivek Nambiar, Gireesh Kumar,
Sreekrishnan T. P., Ajith V, Naveen Mohan
INTRODUCTION
The classification of stroke was
traditionally based on risk factors,
clinical features and findings on
brain imaging studies1. The physician would usually determine
subtypes of ischemic stroke based
on clinical features and results of
diagnostic studies. This non-standardized approach may be acceptable in clinical practice but not for
studies.
TOAST (Trial of Org 10172 in
Acute Stroke Treatment) classification of subtype of acute ischemic
stroke was introduced to produce
uniformity. The TOAST classification (Table 1) system is straight
forward and follows a logical progression1. There are only a few studies evaluating the usefulness of
TOAST classification in predicting
the clinical outcome following an
acute ischemic stroke. Hence, we
planned to evaluate its use in
predicting clinical outcome, in this
study.
Table 1
TOAST CLASSIFICATION
1. Large artery atherosclerosis
2. Cardioembolism
3. Small artery occlusion
4. Stroke of other determined
etiology
5. Stroke of undetermined
etiology
METHOD OF STUDY
Patients presenting to Emergency
Medicine Department of Amrita Institute of Medical Science during
2012–2013 with acute ischemic stroke were studied. Those presenting
within 7 days of onset of stroke and
age>18years were included. Those
Dept. of Emergency Medicine, *Neurology, AIMS,
Kochi.
patients with intracranial hemorrhages were excluded from the
study.
Patients included in the study
were evaluated and initial NIHSS
Score was noted. All patients were
subjected to CT/MRI to diagnose
acute ischemic stroke. MRA/CTA
was done to look for any large
vessel disease. Patients were subjected to electrocardiogram, echocardiography and Holter monitoring for evaluation of any potential
cardio-embolic focus for stroke.
Patients were reassessed for
neurological worsening after 48 hrs
and by the end of 5th day. This was
defined as an increase in NIHSS
score by 2 points from the baseline,
as used in various other studies2,3,4.
This scoring system has been shown
to have good reliability5,6. Patients
were then divided into two groups.
1) Neurological worsening group or
Progressive group.
2) Stable group.
All patients were classified
according to TOAST classification
system. Statistical analysis was then
done between the progressive and
stable group.
STATISTICAL ANALYSIS
1. Percentage of stroke cases with
neurological worsening was computed.
2. To compare categorical variables
Chi square test was applied. The pValue <0.05 was considered as
statistically significant.
Statistical analysis was done using
IBM SPSS Statistics 20.
RESULTS
Total study population was 66,
composed of 52 males (78.8%) and
14 females (21.2%). Neurological
worsening was seen in 16(24.2%)
patients. The study population was
categorized based on the TOAST
classification system.
In our study population of 66
patients, we found that 22 patients
had large vessel disease, 11 had
cardio-embolic source, 9 had small
vessel disease and etiology of 24
patients where unknown. 8 patients
(36.3%) with large vessel disease, 5
(45.4%) patients with cardioembolic source, 2(22.5%) patients
with small vessel disease and 1
patient with unknown etiology had
neurological worsening (Table 2).
The p-value was 0.021, which is
statistically significant.
DISCUSSION
In our prospective study, neurological deterioration was seen in
24.2% of total patients which is comparable to other studies2,3,10 .
Our study also showed that patients with large vessel disease (36.3%)
and cardio-embolic source (45.4%)
are at a great risk for early neurological deterioration when compared to stroke due to small vessel
disease (22.5%) and unknown etiology (4.1%). The p value of classification stroke subtypes based on
TOAST classification was 0.021,
which shows the statistical significance.
Our study clearly shows that
patients with large vessel disease
and cardio-embolic source are at a
greater risk of neurological worsening warranting the need for intravenous thrombolysis or endovascular intervention. Intravenous fibronolytic therapy for acute stroke is
now widely accepted and approved
23
Predicting Clinical Outcome In Acute Ischemic Stroke Based On TOAST Classification
Table 2
Graph 1: TOAST classification among progressive group
worsening, stressing the importance of thrombolysis in
patients with large vessel disease even when they
present with minor stroke (NIHSS≤ 4) with disabling
symptoms. The actual percentage of patients developing neurological worsening is even higher than
demonstrated by us, since our center is tertiary care
where most of our patients are referred at a later stage.
Further studies are required to understand the benefits
of thrombolysis in minor stroke.
CONCLUSION
by US FDA7. AHA Stroke Guidelines recommends to
thrombolyse patients with only measurable neurological deficits; also to avoid thrombolysis in patients
with minor stroke (NIHSS ≤4)7.
But patients with gait disturbance, isolated aphasia or
isolated hemianopia may have potentially disabling
symptoms although their NIHSS score is 2. Eric et al has
shown that in patients with mild or improving stroke in
whom IV tPA was not administrated was associated with
poor outcome8. Steven et al have demonstrated that the
term RISS should be reserved for those who improve to
mild deficit, specifically in whom it is perceived to be
non-disabling9. They have also shown that large artery
occlusion on imaging, despite minor symptoms or
clinical improvement, may identify patients at high risk
of neurological deterioration9.
Krasen et al in his study demonstrated that patients
with persisting proximal vessel occlusion were 7 times
more likely to have an unfavourable outcome at 3
months11. He has also demonstrated that thrombolysis in
a selected group of patients with mild or rapidly
improving stroke is justified and has a favorable
outcome11. This warrants the need for early neurovascular (CTA/MRA) imaging in the emergency department itself and consideration of IV thrombolysis in all
patients with large vessel disease even when the NIHSS
score ≤4 with disabling symptoms. Further studies are
needed regarding the use of IV tPA in patients with
minor stroke.
In our study, we demonstrated that patients with large
vessel disease has greater chance of early neurological
24
TOAST classification is a simple tool which classifies
the stroke patient based on etiology. It is not only a
useful classification system for studies, but also for
predicting the prognosis of patients presenting with
acute ischemic stroke. We found that patients with large
vessel disease and cardio-embolic source tend to have
early neurological deterioration. We suggest
considering IV tPA even in patients with minor stroke
with disabling symptoms.
LIMITATION
The sample size of our study is small, even though we
could demonstrate with statistical significance that
TOAST classification is a simple classification based on
etiology and can predict the prognosis based on the
TOAST sub category.
Those patients who worsened prior to presenting to
our center were not excluded from the study, implying
that the actual number of patients developing neurological worsening is even more.
ABBREVIATIONS
TOAST : Trial of Org 10172 in Acute Stroke Treatment
NIHSS : National Institute of Health Science Score
CT
: Computerised Tomography
MRI
: Magnetic Resonance Imaging
CTA
: Computerised Tomography Angiography
MRA
: Magnetic Resonance Angiography
ASA
: American Stroke Association
tPA
: Tissue Plasminogen Activator
RISS
: Rapidly Improving Stroke Symptoms
ACKNOWLEDGEMENTS
1. All the staff of Department of Emergency Medicine
and Critical Care, Amrita Institute of Medical Sciences,
Kochi. Special Thanks to Dr. Elson.
2. Department of Biostatistics, Amrita Institute of
Medical Sciences, Kochi.
References
1. Harold P. Adams Jr, Birgitte H. Bendixen, et al and TOAST Investigators. Classification of subtype of acute ischemic stroke: Definitions
for use in multicentric clinical trial. Stroke 1993; 24:35 -41.
2. J. Kwan & P. Hand. Early neurological deterioration in acute stroke:
Clinical characteristics and impact on outcome. QJ Med 2006;
99:625-33.
3. Cheung-Ter ong & Chi shan wu. Neurological deterioration in
patients with first ever ischemic stroke. Acta Neurol Taiwan. 2007;
16(3):143-9.
4. L.E. Craig O. Wu H. Gilmour M. Barber P. Langhorne. Developing
and Validating a Predictive Model for StrokeProgression. Cerebrovasc
Dis Extra. 2011;1:105-14.
5. Lyden N, Raman R, Liu L, et al. National Institutes of Health Stroke
Scale certification is reliable across multiple venues. Stroke.2009
Jul;40(7):2507-11.
6. Goldstein LB, Samsa GP. Reliability of the national institutes of
health stroke scale. Extension to non-neurologist in the context of a
clinical trial. Stroke. 1997 Feb;28(2):307-10.
7. Edward C. Jauch, Jeffrey L. Saver, Harold P. Adams Jr, et al.
Guidelines for the Early Management of Patients With Acute Ischemic
Stroke: A Guideline for Healthcare Professionals From the American
Heart Association / American Stroke Association. Stroke. 2013 Mar;
44(3):870-947.
8. Smith EE, Abdullah AR, Petkovska I, et al. Poor outcomes in patients
who do not receive intravenous tissue plasminogen activator because of
mild or improving ischemic stroke. Stroke. 2005 Nov;36(11):2497-9.
9. Steven R. Levine, Pooja Khatri, Joseph P. Broderick, et al. Review,
Historical Context, and Clarifications of the NINDS rt-PA Stroke Trials
Exclusion Criteria: Part 1:Rapidly Improving Stroke Symptoms. Stroke.
2013 Sep;44(9):2500-5.
10. Yousry Abo El- Naga. Predictors of early progression in ischemic
stroke. Egypt J. Neurol. Psychiat. Neurosurg. 2007;44(1):207-23.
11. Krassen Nedeltchev, Benjamin Schwegler, Tobias Haefeli, et al.
Outcome of Stroke With Mild or Rapidly Improving Symptoms.
Stroke. 2007;38:2531-5.
25
Vol. 11, NO: 2
July - Dec 2015, Page 1 - 44
ORIGINAL ARTICLE
A Study on Obstetric and Ultrasonographic Parameters
in Patients with Early Miscarriage
Parvathy Ganesan, Deepthi Sharma, Sudha.S, Radhamany.K
ABSTRACT
Aim: To assess factors including yolk sac diameter and morphology associated with miscarriage.
Materials and Methods: This was an observational study carried out in the Department of Obstetrics and Gynaecology, Amrita
Institute of Medical Sciences, Kochi from September 2013 to August 2014. A total of 50 subjects who had miscarriage were
analyzed for factors associated with it including age, parity, duration of married life, co-existing medical disease, gestational age
(assessed by last menstrual period, mean gestational sac diameter and crown-rump length), gestational sac (GS) morphology, yolk
sac (YS) diameter and morphology.
Results: The mean age was 27.48+/- 4.2 years and mean duration of married life was 4.3+/- 3.4 years. Fetal pole was absent in
44%. GS and YS morphology was normal in 64% and 68% respectively. Echogenic YS was seen in 4%. YS diameter was <2mm in
2%, 2-6 mm in 58% and > 6mm in 24%. Mean gestational age assessed by last menstrual period (LMP) and mean gestational sac
diameter (MSD) was 8w 4d ± 1w4d and 7w3d ± 1w1d respectively.
Conclusion: Abnormalities in diameter and morphology of YS and GS are seen to be associated more with miscarriages. Disparity
between LMP GA, CRL GA and MSD GA may point towards a possible miscarriage. It may be stressed that routine assessment and
documentation of YS and GS diameter and morphology in all early pregnancy scans might help in predicting chances of
miscarriage.
Key words: Gestational age, Yolk sac, Gestational sac, Miscarriage
INTRODUCTION AND
BACKGROUND
Accurate differentiation between
normal pregnancy and pregnancy
loss in early gestation remains a clinical challenge1. Previous studies
have described the association between embryonic well-being and the
characteristics of gestational sac
(GS), yolk sac (YS), amniotic cavity,
and embryonic heart beat2 .Two
dimensional USG remains a simple
and convenient way to assess pregnancy status. There are discriminatory criteria in predicting spontaneous pregnancy loss. These include 8 mm mean sac diameter
(MSD) without YS, 16- 20 mm MSD
without fetal cardiac activity etc.
However, variations and exceptions
exist in these3.The transvaginal
probe has revolutionized the assessment of early pregnancy providing
better spatial resolution and improved diagnostic accuracy4.
The first definitive sonographic
finding to suggest early pregnancy is
the GS. First embryonic structure
seen in a GS is the YS. It may be
visible as early as 5th week when
the MSD is around 5mm5. During
Dept. of Obstetrics & Gynaecology, AIMS, Kochi.
26
embryonic development, the yolk
sac is the primary route of exchange
between the embryo and the mother. Yolk sac supplies iron, calcium, cholesterol and folic acid and
that is the reason why maternal
nutrition and folic acid supplementation has a role in early organogenesis. During the process of
neuralization, nutrients are absorbed by endocytosis in the endoderm
derived cell layer of yolk sac. Aberrations in this is said to be one of the
etiologic factors contributing to
development of Neural Tube defects (NTDs)6. Therefore, the yolk
sac is crucial in early embryonic
life.
YS is always seen by 5.5 weeks
of GA when the MSD is around
8mm. If not seen, pregnancy is not
viable in most of the cases. Its
diameter increases steadily between 5-10 weeks of gestation to a
maximum of 5-6mm. By the end of
first trimester, YS is no longer seen
and it gets absorbed into the umbilical cord7. Much debate has occurred regarding abnormalities of YS
including abnormal size and shape,
calcification, echogenic YS etc. Calcified YS is reported in dead em-
bryo, echogenic YS is seen associated with poor prognosis. Abnormally large YS was found to be
associated with trisomy 21, partial
As shown in Table 1, the observed
diameter of the yolk sac with relation to gestational age was described
by Faye et al.8
Table 1 - Yolk sac diameter in various gestational ages
Gestational
Age (weeks)
Sonographic mean
diameter of yolk sac
(Mean ±Standard Deviation)
6
3.01± 0.75
7
3.99± 0.86
8
4.72± 0.64
9
5.22± 0.63
10
5.89± 0.56
YS diameter 2-6 mm is a favorable
marker for viable pregnancy. The
ongoing pregnancy rate when YS
diameter ranged 2-6 mm was
85.3%. Only 20% had ongoing pregnancy when YS diameter was <
2mm or > 6mm. There is also an
association between MSD and early
pregnancy loss (EPL) 9.
Systematic review by Tom Bourne
et al (2012) looked at the evidence
behind existing standards in definition of EPL. But
findings were limited by small number and poor quality
of studies. The study concluded that we urgently require
further studies before setting future standards for
accurate diagnosis of early embryonic demise10.
AIM
To assess factors including yolk sac diameter and
morphology associated with miscarriage.
MATERIALS AND METHODS
This was an observational study conducted on 50
subjects coming for early pregnancy scan and was
diagnosed as having miscarriage. This was done in the
Department of Obstetrics and Gynecology, Amrita Institute of Medical Sciences, Kochi from September 2013
to August 2014.
Approval from the institutional review board was
obtained prior to the recruitment of subjects. The history
and demographic data were obtained from the subjects.
Ultrasonography was done for all subjects using transvaginal probe with frequency of 8MHz. The standard
guidelines for obtaining the sonographic measurements
and observations were strictly followed.
Yolk sac was visualized and the diameter was
measured using electronic calipers taking inner to inner
diameter and it was recorded as normal (< 6mm), large
(> 6mm) or small (< 2mm). The morphology of the
yolk sac was also assessed; whether its outline was
normally rounded and regular or irregular. If irregular,
its mean diameter and largest diameter were recorded.
Any abnormal changes like echogenicity or calcifications were also noted.
The mean gestational sac diameter was calculated by
measuring three orthogonal dimensions of the chorionic
cavity (excluding the surrounding rim of echogenic
tissue) and taking the mean. The morphology of the
gestational sac was also noted.
The crown rump length (by Hadlock's formula) and
other essential sonographic features like choriodecidual
reaction, presence and size of any subchorionic hematoma was also recorded.
The measurements were taken by operators trained
in doing ultrasonography. All the measurements were
recorded in the computer during the sonography.
Majority of the recordings were done by or in the
presence of the principal investigator. If done by a
second person in the absence of the principal
investigator, the findings recorded in computer were
assessed by the principal investigator afterwards. This
method helped in reducing the inter-observer
variations. The measurements recorded were also
randomly assessed by a second investigator and this
helped in reducing the bias. All the data including the
follow up were recorded against the patient's
identification number.
We took the sample size of fifty as this was the
number of subjects available with miscarriage during
the time period. We aimed to take all cases of
miscarriage during the period, a method of convenient
sampling.
All the data collection was done using Microsoft
office excel spread sheet and analysed for factors
influencing miscarriage. Descriptive statistics like
frequency and percentage was used whenever
applicable. Mean and standard deviation was
calculated under measures of central tendency for
certain variables. Statistical software used was SPSS
version 20.0
RESULTS
Majority of the patients were primi gravidas (62%). A
total of 19 patients (38%) had associated medical comorbidities. These included hypothyroidism (16%),
PCOS (8%), epilepsy (2%), congenital heart disease
(2%), overt diabetes (2%), hypertension (2%), APLA
syndrome (2%), anaemia (2%) and Nephrotic
syndrome (2%). (Table 2 & 3)
Table 2 - Parity and medical co morbidities
Parameter
Number
Percentage
Parity Primi
31
62
Multi
19
38
Medical
Present
19
38
Co morbidities
Absent
38
62
Table 3 - Details of Medical co morbidities associated
Disease
Number
Percentage
Hypothyroidism
8
16
PCOS
4
1
2
Cong. Heart
Disease
1
2
Overt DM
1
2
Hypertension
1
2
APLA
1
2
Anaemia
1
2
Nephrotic
Syndrome
1
2
Epilepsy
8
The mean age of the patients in the group was 27.5
±4.2 years. The mean duration of married life was
4.3± 3.4 years. The mean gestational age (GA) as
calculated from last menstrual period (LMP) was 8
weeks + 4 days and that calculated from mean sac
diameter (MSD) was 7weeks + 3 days. (Table 4)
Table 5 shows the GA distribution as calculated from
LMP, MSD and crown rump length (CRL). Majority had
GA between 8 and 9 weeks (34%) as calculated by
LMP. However, when calculated by CRL and MSD
showed that majority had GA between 6 and 7 weeks
27
A Study on Obstetric and Ultrasonographic Parameters
in Patients with Early Miscarriage
(30% and 42% respectively). There were 22 patients
who didn't have a visible fetal pole at diagnosis of
miscarriage.
Table 4 - Age, Duration of Married Life and Gestational Age
Parameter
Standard
deviation
Mean
Age
27.5yrs
4.2yrs
Married Life
4.3yrs
3.4yrs
LMP GA
8w+ 4 d
1w + 4d
MSD GA
7w +3d
1w+1d
Table 6 - Sonographic parameters
GS morphology
Regular
32
64
Irregular
18
36
YS diameter
<2mm
01
02
2 - 6mm
29
58
>6mm
12
24
NA
08
16
YS morphology
Table 5 - Comparison of GA assessed by different methods
Parameter LMP GA CRL
No %
<6 wks
02 04
GA MSD GA
No
%
02 04
No
6w - 6w 6d
07 14
15 30
21 42
7w - 7w 6d
07 14
06 12
06 12
8w - 8w 6d
17 34
03 06
04 08
9w - 9w 6d
08 16
01 02
02 04
≥ 10 w
09 32
01 02
01 02
22 44
-
NA
Mean±SD
-
-
8w 4d ±
1w4d
__
-
7w3d ±
1w1d
LMP - Last menstrual period, CRL - Crown rump length, MSD - mean
sac diameter, GA - Gestational age, NA - Not applicable.
The data is demonstrated in figure 1.
25
20
15
LMP GA
10
MSD GA
CRL GA
5
0
<6w
6w-6w6d 7w-7w6d
8w-8w6d 9w-9w6d
>10w
NA
LMP - Last menstrual period, CRL - Crown rump length, MSD - mean
sac diameter, GA - Gestational age, NA - Not applicable.
Other sonographic parameters are shown in table 6.
The morphology of the gestational sac (GS) and that of
the yolk sac (YS) was regular in 64% and 68% respectively. YS was irregular in 12% and was echogenic
in 4%. YS diameter was < 2 mm in 2% (Small YS), 2-6
mm in 58% and > 6 mm (large YS) in 24%. YS diameter
and morphology was not applicable in 16% as these
patients didn't have a visible YS.
The presence of a subchorionic hematoma was
identified in only 6% of the patients. The choriodecidual reaction was good in 40%, average in 44%
and poor in only 16%.
28
SCH
%
16 32
Number Percentage
Parameter
CDR
Regular
34
68
Irregular
06
12
Echogenic
02
04
NA
08
16
Present
03
06
Absent
47
94
Good
20
40
Average
22
44
Poor
08
16
GS - Gestational Sac, YS - Yolk sac, SCH - Sub chorionic Hematoma,
CDR - Chorio decidual reaction
DISCUSSION
During the first trimester of pregnancy, a unique and
dramatic sequence of events occur defining the most
critical and tenuous period of human development, the
transformation of a single cell into a recognizable
human being. Because of the complex events that
accompany first trimester development, it is not unusual
for complications to occur. Approximately 15% of
clinically recognized pregnancies are miscarried. The
loss rate is stipulated as 2-3 times higher with very early
and clinically unrecognized pregnancy8.
This was an observational study done in 50 patients
with early pregnancy and was diagnosed as having miscarriage. Majority of the patients in the group were
primigravidas (62%). Remaining 38% were multigravidas. The miscarriage rate was higher in primigravidas.
A total of 19 patients (38%) were having some co
existing medical illness. Majority had hypothyroidism
(16%) and PCOS (8%). It may be prudent to give special
attention in the preconceptional counselling of patients
presenting with such medical illnesses.
The mean age was 27.5±4.2 years. The mean
duration of married life was 4.3±3.4 years. This shows
that advanced age and prolonged duration of married
life, even though might be contributing to miscarriage,
were not found to be significantly associated in our
group.
Gestational age (GA) was calculated from LMP, MSD
and CRL. The GA was different when calculated from
CRL and MSD as compared to that calculated from LMP.
GA calculated from MSD was less than that from LMP in
the group (7W 3d ± 1W 1d vs 8W4d±1W 4d respectively). Fetal pole was absent in 44% and out of the
remaining 56% in whom CRL GA was obtained, it was
consistently less than that calculated from LMP.
However, the disparity was more pronounced between
LMP GA and MSD GA than that between LMP GA and
CRL GA. Hence, even if CRL GA is corresponding to
LMP GA, small MSD may independently predict
miscarriage. Similarly even if MSD is corresponding,
small CRL might be indicative of miscarriage.
In 2011, the first systematic review of the evidence
behind the diagnostic criteria for miscarriage was
published. It states, "Findings were limited by the small
number and poor quality of the studies," and concluded
that further studies were, “urgently required before
setting future standards for the accurate diagnosis of
early embryonic demise.” This implies that data used to
define criteria to diagnose miscarriage are unreliable.
The 2011 Irish Health Service executive review into
miscarriage misdiagnosis highlighted this issue. So it is
surprising how little evidence exists to support previous
guidance10.
Irregular GS morphology was seen in 32% of
miscarriages. Remaining 68% had regular GS morphology. Even though the incidence of irregular GS was
only 32%, its presence might be a marker to predict
miscarriage. Irregular GS is sometimes associated with
adenomyosis or leiomyoma or uterine abnormalities,
the conditions which are usually attributed to cause
increased incidence of miscarriage. Hence, it can be
recommended that GS morphology need to be mentioned in all routine early pregnancy scans as it might be
contributory in predicting or diagnosing miscarriage.
Yolk sacs with mainly wrinkled margins, indented
walls, or both are usually identified as having an
irregular shape11. The clinical importance of an abnormal yolk sac shape is controversial and thus, still under
debate. There are a number of clinical studies that have
declared that the persistence of an irregular yolk sac
shape may be used to indicate an adverse gestational
outcome. There is one study reporting that an echogenic
yolk sac can be associated with fetal death or abnormalities12. However, an echogenic yolk sac is not associated with anomalies or a poor pregnancy outcome
according to Sinan Tan et al5. It has also been anecdotally emphasized that an echogenic yolk sac does not
predict an embryonic anomaly or death.
In their review, Sinan Tan et al concluded that largescale prospective studies are anticipated to clarify the
prognostic importance of echogenic yolk sacs5. We got
irregular yolk sac in 12% of miscarriages. YS was absent
in 16%, echogenic in 4% and with normal morphology
in remaining 68%. Our findings don't support a significant role of YS morphology in predicting miscarriage.
However, presence of irregular or echogenic YS may
warrant careful follow up with serial sonograms.
Although there is no clearly identified consensus,
most authors accept either 5 or 6 mm as the upper limit
for the size of a normal yolk sac in pregnancies with a
Possible Predictors of Miscarriage
Disparity between LMP GA, CRL GA and MSD GA YS
diameter >6mm
Irregular YS morphology
Irregular GS morphology
Small YS, echogenic YS, Presence of SCH, Poor/Average CDR were not good predictors
Age, parity and duration of married life are not much
predictive of possible.
gestational age from the 5th to the 10th weeks13. In our
series, YS was large (> 6 mm) in 24%, small (< 2 mm)
in 2% and normal (2-6 mm) in 58%. YS was absent in
remaining 16%. In those who had a yolk sac (42 patients), it was large in 12, small in one patient and normal
in remaining 29. It may be concluded that large YS is a
significant predictor of miscarriage and small yolk sac
may not be having much clinical significance. However, a few authors have mentioned the existence of a
very large yolk sac in a normal live pregnancy14. Generally, it has been suggested that an abnormally large
yolk sac may indicate a poor obstetric outcome; therefore, close follow-up with sonography is recommended
for these pregnancies5.
The presence of subchorionic hematoma was found
in only 6% of the patients. The choriodecidual reaction
was poor in only 16% of the cases with miscarriage.
These were not having much predictive significance.
CONCLUSION
Abnormalities in diameter and morphology of yolk
sac and gestational sac are seen to have more association with miscarriages. Routine assessment and
documentation of yolk sac and gestational sac diameter
and morphology in all early pregnancy scans might help
to predict chances of miscarriage. With the advent of
high resolution ultrasound, the conventional cutoffs of
MSD and CRL in diagnosing miscarriage needs reappraisal.
Acknowledgement
We sincerely thank Dr. Sarala Sreedhar, Professor,
Obstetrics and Gynecology & Dr. Jayashree, Professor,
Obstetrics and Gynecology for their encouragement &
support. We are also thankful to Dr. Sundaram K.R,
Professor and Head, Department of Biostatistics, Amrita
institute of medical sciences, Kochi for his constant
support during the statistical analysis and study design.
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without a demonstrable embryo; Ultrasound Obstet Gynecol.
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4. Susan E. Rowling, Beverly G.Coleman, Jill E. Langer, et al. Radiology Dec 1997; 203: 211-7.
29
A Study on Obstetric and Ultrasonographic Parameters
in Patients with Early Miscarriage
5. Tan S, Pektaş MK, Arslan H. Sonographic evaluation of the yolk sac;
J Ultrasound Med. 2012 Jan;31 (1):87-95.
6. Daniel J.Lindsay, Ian S. Lovett, Edward A. Lyons, et al. Radiology
1992 Dec; 183: 115-8.
7. Nyberg DA, Mack L, Laing FC : Distinguishing normal from abnormal gestational sac growth in early pregnancy. J ultrasound med, 6;
23, 1987.
8. Faye C. Liang, Mary C. Frates, Carol B Benson; ultrasound evaluation during first trimester of pregnancy, Text book of Ultrasonography in Obstetrics and Gynecology, Saunders: 5th edition;
2008
9. Soyoung Bae, Joseph Karnitis; Triple ultrasound markers including
fetal cardiac activity are related to miscarriage risk. Fertil Steril 2011
Nov; 96 (5):1145- 8.
30
10.Tom Bourne and Cecilia Bottomley; When is a pregnancy
nonviable and what criteria should be used to define
miscarriage?Fert Steril Nov 2012;98 (5):1091- 7
11. Tan S, Ipek A, Pektas MK, et al. Irregular yolk sac shape: is it really
associated with an increased risk of spontaneous abortion? J
ultrasound Med 2011; 30: 31-6.
12. Szabo J, Gellén J, Szemere G, et al. Significance of hyperechogenic yolk sac in first-trimester screening for chromosome
aneuploidy [in Hungarian].Orv Hetil 1996; 137: 2313–5.
13. Levi CS, Lyons EA, Dashefsky SM, et al. Yolk sac number, size and
morphologic features in monochorionic monoamniotic twin
pregnancy. Can Assoc Radiol J 1996; 47:98–100.
14. Cho FN, Chen SN, Tai MH, et al. The quality and size of yolk sac in
early pregnancy loss; Aust NZ J Obstet Gynecol 2006; 46: 413-8.
Vol. 11, NO: 2
July - Dec 2015, Page 1 - 44
ORIGINAL ARTICLE
Chronic Pancreatitis: Experience of the last 15 years in the
Pancreas Clinic at AIMS.
G. Rajesh, V. Balakrishnan
INTRODUCTION
Chronic pancreatitis (CP) is a
progressive inflammatory disease of
the pancreas characterized by irreversible morphological changes
typically causing pain and/or permanent loss of function. Tropical
pancreatitis was considered the
dominant etiology in Kerala unlike
Western countries and Japan where
alcohol is the most common cause
of CP1. Tropical pancreatitis is characterized by abdominal pain, large
intraductal calculi, diabetes mellitus, complicated by a high incidence of pancreatic cancer seen in
young, non-alcoholic subjects2.
While the traditional risk factors
implicated in TCP included malnutrition, dietary toxins and environmental agents, there is increasingly
emerging evidence about the role of
genetic factors3,4. However, patients
similar to those described as tropical
pancreatitis comprised only 3.8% in
a large multicentre study comprising 33 centres in India where
AIMS, Kochi was the lead centre5.
There has been a rising trend in
alcohol consumption in Kerala
which has the highest per capita
consumption of alcohol among
Indian states4,6,7. We report our experience in managing chronic pancreatitis over the last 15 years at the
Pancreas clinic at Amrita Institute of
Medical Sciences(AIMS), Kochi.
PATIENTS AND METHODS
The Pancreas clinic at AIMS,
Kochi has been managing patients
with pancreatic diseases including
chronic pancreatitis from all over
the state of Kerala. We have prospectively followed up the patients
and maintained an electronic
database. Chronic pancreatitis is
Dept. of Gastroenterology, AIMS, Kochi.
diagnosed on basis of standard criteria in patients with typical clinical
and imaging (US/CT/ERCP/MRCP/EUS). A detailed assessment of alcohol intake and smoking habits is
performed using a standard proforma administered by a trained
medical social worker. Alcoholic
chronic pancreatitis (ACP) is diagnosed in CP patients who have been
consuming >80 g alcohol/day for
at least 5 years. Idiopathic chronic
pancreatitis (ICP) is diagnosed if
pre-existing conditions likely to
cause CP (primary hyperparathyroidism, hypertriglyceridemia, hereditary pancreatitis, and other rare
causes as well as excess alcohol
consumption) were ruled out. Autoimmune pancreatitis is diagnosed
as per previously reported criteria.
RESULTS
A total of 1157 patients (822
males, 335 females) with chronic
pancreatitis were enrolled in our
Pancreas clinic between 1999 and
2014. The mean age of diagnosis
was 41.4+/- 13.9 years.
The most common form of CP
was ICP (720 patients) which comprised nearly 2/3 of patients with
CP. ACP (412 patients) comprised
nearly one-third of the patients and
prevalence was seen to be increasing over the years. In recent years,
there has been increased detection
of rare causes of CP like hypercalcemia related CP(11patients),
hypertriglyceridemia related CP(2
patients), and autoimmune pancreatitis (3 patients). However, these
entities comprised less than 2% of
CP patients. Cases of CP where viral
infections8, drugs and medications
possibly had a role were also noted
in our series. Genetic factors were
studied in some of our patients and
common mutations which were
detected included SPINK1, CFTR
and CASR gene mutations9. Familial
aggregation was not uncommon in
TCP10.
The most common and predominant symptom was pain, seen in
1041 (89.9%) patients. Calcification
was seen 1040 (89.8%) patients.
Diabetes was seen in 665 (57.4%)
patients while steatorrhea, in 390
(33.7%) patients. Our findings
corroborate the value of using fecal
elastase1 estimation by polyclonal
ELISA kit as a valuable method for
testing for pancreatic exocrine
insufficieincy11. The nutritional status
was evaluated by anthropometric,
biochemical, clinical assessment and
a detailed dietary assessment was
done. We found that severe
malnutrition was less common than
in previously reported series12,13.
Cassava was not found to be a significant dietary factor as was previously
considered14. Selective deficiencies
in branched-chain amino acids were
seen15. Significantly, we noted deficiencies in micronutrients especially
zinc and folic acid in both ACP and
TCP patients16-18.
Diabetes could be managed
purely by dietary measures in a
minority. Most needed use of OHAs
or insulin. Pancreatic exocrine insufficieincy (PEI) responded to pancreatic enzyme supplements (pancrealipase/pancreatin) and dietary
measures. Use of minimicrosphere
pancrealipase preparations was
especially useful in cases of severe
PEI (fecal elastase1 levels <100mg/g stool) and following pancreatico-duodenectomy. Pancreatic
pain could be managed with medical management in the majority.
31
Chronic Pancreatitis: Experience of the last 15 years in the Pancreas Clinic at AIMS
Common interventions for pain included endotherapy
with ERCP , ESWL, and celiac plexus block (fluoroscopy or EUS guided).
Common local complications noted included
pancreatic pseudocysts, pancreatic ascites, and benign
biliary strictures. Endoscopic pseudocyst drainage
(transgastric and transpapillary approaches) was
successful in most patients with pseudocysts but needs
proper case selection to identify cases likely to resolve
without need for subsequent surgical drainage.
However, endoscopic management was successful in
most cases of pancreatic ascites corroborating use of
endotherapy as a first line of management in this
complication. Splenic and SMA pseudoaneurysms
with GI bleed were most common vascular
complications.
Pancreatic cancer complicating CP was seen in
patients and was diagnosed late in most patients. Early
diagnosis of pancreatic cancer in setting of CP and
differentiation of benign and malignant mass in CP
remain formidable clinical challenges despite medical
advances. We found serum CA 19-9 was a valuable
adjunct in diagnosis and management of pancreatic
cancer and may possibly be used for screening. EUS
was useful in evaluation of CP. However, the dense
calculi burden in our CP patients, unlike in the West,
appeared to reduce its value in differentiating a benign
from malignant mass on a basis of sonographic
morphology alone and in detecting very small lesions
which are not seen on CT scan. EUS guided FNA was
used in patients and was useful when a positive result
was obtained. However, a negative FNA result could
not conclusively exclude malignancy.
We have previously reported differences in drinking
patterns between alcoholic liver cirrhosis(ALC) and
alcoholic chronic pancreatitis (ACP). Older age of onset
of disease, longer duration of drinking, and higher
cumulative alcohol intake were seen in ALC. ALC
patients were more often continuous drinkers and
alcohol dependents whereas ACP patients were more
often binge drinkers and tended to abstain more often.
ACP patients were also more often smokers than ALC
patients20.
Regular 3-6 monthly counselling sessions in our
clinic helped achieve significant reductions in cessation
of alcohol and smoking.
DISCUSSION
TCP had been the dominant type of CP in Kerala and
typically had a clinical presenation of “pain in childhood, diabetes in adolescence and death during prime
of life”. A significant finding in our experience over the
last 15 years has been a delay in age of onset of CP.
Overall, the reasons behind this seem related to
increase in prevalence in ACP (which is known to
present later after several years of alcohol abuse); as
well as change in the natural history of ICP patients who
32
now appear to present later and have a seemingly
milder course. The possible reasons for the latter
include better socioeconomic conditions, improvements in health facilities, and diet of the people in
Kerala. There is still lack of a definite understanding of
the etiopathogenesis of TCP. It is likely that there is an
interaction of multiple genetic and environmental
factors. Oxidative stress and antioxidant depletion
appear to be a common pathogenetic mechanism in
chronic tissue inflammation and injury. Micronutrient
deficiency could impact pancreatic function as some of
these do appear to play a vital though often not well
characterized role in pancreatic function. Alternatively,
micronutrient deficiency could be implicated in production of oxidative stress which is well known to be
implicated in pathogenesis of CP. Supplementation of
folic acid and zinc could be useful additions to
traditional antioxidant preparations used for medical
management of CP.
Moreover, the etiologies of CP are getting blurred
with increase in alcohol use in the population. Unlike
previously where ICP patients were mostly patients
who never consumed alcohol, now many of them
imbibe alcohol in small amounts. Thus, there is a mixed
picture. The classical tropical pancreatitis is seldom
seen now. A rise in prevalence of smoking has also been
noted which is a risk factor in progression of disease
especially in development of early calcification and is
also an independent risk factor for pancreatic cancer.
We observed a rise in proportion of ACP cases
which now comprise about one-third of CP cases with
increasing prevalence over the last few years. The rise in
ACP reflects an increase in alcoholism in Kerala. This
disturbing trend needs to be addressed by appropriate
interventional measures.
Apart from alcohol abuse and smoking, there is also
an increased consumption of high fat, high caloric foods
associated with increased prevalence of metabolic
syndrome. Hence,high BMI and related metabolic
factors appear to form the background in a subset of CP
cases today21. Lifestyle interventions are likely to be
beneficial and may find a place in the management of
CP in this setting.
We also feel that our approach of health care delivery
through a Pancreas clinic22 with dedicated personnel
capable of offering clinical care, patient education,
regular follow-up and documentation is useful in
providing comprehensive care resulting in a significant
improvement in quality of life for this chronic disease.
This clinic includes a gastroenterologist with special
interest in pancreatic diseases (pancreatologist) along
with a team comprising of clinic coordinator, social
worker, and dietician working in close collaboration,
and a diabetologist. Our clinic has managed to achieve
substantial improvements in alcohol and smoking
cessation and decreased need for interventions for pain.
References
1. Balakrishnan V. Tropical chronic pancreatitis: a historical
perspective. Gut. 2011 Oct;60(10):1441.
2. Balakrishnan V (ed). Chronic Pancreatitis in India. Tri-vandrum:
Indian Society of Pancreatology, 1987.
3. Balakrishnan V, Kumar H, Sudhindran S, et al . Chronic Pancreatitis
and Pancreatic Diabetes in India. Kochi: Indian Pancreatitis Study
Group, 2005.
4. Balakrishnan V, Nair P, Radhakrishnan L, Narayanan VA. Tropical
pancreatitis - a distinct entity, or merely a type of chronic pancreatitis?
Indian J Gastroenterol 2006; 25:74–81.
5. Balakrishnan V, Unnikrishnan AG, Thomas V, et al. Chronic
pancreatitis. A prospective nationwide study of 1,086 subjects from
India. JOP 2008; 2:593–600.
6. Rajesh G, Girish BN, Panicker S, et al. Time trends in etiology of
chronic pancreatitis in South India. Tropical Gastroenterology
2014;35(3):164-7.
7. Rajesh G, Veena AB, Saumya M, et al. Clinical profile of early-onset
and late-onset idiopathic chronic pancreatitis in Southern India.
Indian J Gastroenterol. 2014;. 33(3):231-6.
8. Rajesh G, Nair AS, Narayanan VA, et al. Acute pancreatitis in viral
infections woth possible progression to chronic pancreatitis. Indian J
Gastroenterol. 2008 Jul-Aug; 27(4):162-4
9. Rajesh G, Elango EM, Vidya V, et al. Genotype phenotype
correlations in 9 patients with tropical pancreatitis and identified gene
mutations. Indian J. Gastroenterol. 2009; 28:68–71.
10. Rajesh G, Nair AS, Narayanan V, et al. Tropical pancreatitis and
fibrocalculous pancreatic diabetes – two sides of the same coin?
Tropical Gastroenterol. 2008; 29:175–6.
11. Girish BN, Rajesh G, Vaidyanathan K, et al. Fecal elastase 1 and
acid steatrocrit estimation in chronic pancreatitis. Indian J of
Gastroenterol 2009; 28:201–5.
12. Balakrishnan V, Sauniere JF, Hariharan M, et al. Diet, pancreatic
function, and chronic pancreatitis in Southern India and in France.
Pancreas 1988; 3:30–5.
13. Tinju J, Reshmi S, Rajesh G, et al. Anthropometric, biochemical,
clinical and dietary assessment of malnutrition in chronic pancreatitis.
Trop. Gastroenterol. 2010;31(4):285-90.
14. Girish BN, Rajesh G, Vaidyanathan K, et al. Assessment of cassava
toxicity in patients with tropical pancreatitis. Trop. Gastroenterol.
2011; 32(2):112-6.
15. Girish BN, Rajesh G, Vaidyanathan K, et al. Alterations in amino
acid levels in chronic pancreatitis. JOP. 2011; 12(1):11-8.
16. Girish BN, Vaidyanathan K, Rao AN, et al. Chronic pancreatitis is
associated with hyperhomocysteinemia and derangements in
transsulfuration and transmethylation pathways. Pancreas. 2009;
10:651–6.
17. Rajesh G, Girish BN, Vaidynathan K, et al. Folate deficiency in
chronic pancreatitis. JOP.2010; 11(4):409-10.
18. Girish BN, Rajesh G, Vaidyanathan K, et al. Zinc status in chronic
pancreatitis and its relation with exocrine and endocrine
insufficiency. JOP 2009; 10:651–6.
19. Girish BN, Rajesh G, Vaidyanathan K, et al. Assessment of
oxidative stress in chronic pancreatitis and its relation with zinc status.
Indian J Gastroenterol. 2011;30(2):84-8.
20. Veena AB, Rajesh G, Varghese J, et al. Alcoholic chronic
pancreatitis and alcoholic liver cirrhosis: differences in alcohol use
habits and patterns in Indian subjects. Pancreas 2012;41:703-6.
21. Rajesh G, Kumar H, Menon S, et al. Pancreatitis in the setting of
the metabolic syndrome. Indian J Gastroenterol. 2012;31(2):79-82.
22. Balakrishnan V, Rajesh G, Lakshmi R, et al. The impact of a
multidisciplinary, comprehensive care model in chronic pancreatitis
on patient perceptions and quality of life. Amrita Journal of Medicine.
2013.
33
Vol. 11, NO: 2
July - Dec 2015, Page 1 - 44
CASE REPORT
Escape From Disseminated Melioidosis Of Tropics: A Case
Report And Literature Review
Naveen Mohan, Priya R. Menon, Gireesh Kumar K.P, . Sreekrishnan T.P,
Ajith Kumar J, Bharath Prasad S, Ajith V, Krupanidhi Karunanithi, Arun Kumar K.
ABSTRACT
Melioidosis is an uncommon environmental disease prevalent in South-east Asia, caused by Burkholderia pseudomallei. It has
been reported very rarely from Kerala. We report the case of a 39-year-old male Indian farmer diagnosed with this infection.
Accurate early microbiological diagnosis, septic foci drainage and effective antibiotic treatment of melioidosis with ceftazidime
salvaged the patient's life and he was discharged totally cured. Presenting clinical features, diagnosis, management and relevant
literature are discussed.
Key words: Burkholderia pseudomallei; water borne; septic arthritis; acute disseminated melioidosis; ceftazidime.
INTRODUCTION
The facultative intracellular aerobic motile non spore-forming Gram
negative bacterium Burkholderia
pseudomallei (formerly known as
Pseudomonas pseudomallei, Bacillus pseudomallei , Bacillus whitmorii or Bacille de Whitmore, Malleomyces pseudomallei) is an environmental saprophyte found in soil
and fresh surface water of endemic
areas and was first isolated in 1911
by Captain A. Whitmore, a British
pathologist at Rangoon General
Hospital1. The diseases caused by
the organism were first known as
Whitmore's disease and in 1921,
the term melioidosis was coined.
The disease resembles glanders, a
pulmonary disease in asses caused
by Pseudomonas mallei. Synonyms
include Pseudoglanders, Vietnamese time bomb, Whitmore's disease
and Rangoon beggar's disease2.
Melioidosis has been a major cause
of morbidity and mortality resulting
in serious public health hazards and
has significant economic consequences3-5. It is prevalent in southeastern Asia and northern Australia6,7
and is the most common cause of
community-acquired bacteremia
pneumonia8. The bacterium is
resistant to penicillin, ampicillin,
first and second-generation cephalosporins, gentamicin, tobramycin,
and streptomycin. Infection is either through inhalation of contamiDept. of Emergency Medicine & Critical Care,
AIMS, Kochi.
34
nated dust or water droplets,
ingestion of contaminated water, or
contact with contaminated soil,
through skin abrasions. The bacterium can survive in a variety of
hostile conditions, including nutrient deficiency, acidic and alkaline
environment, disinfectant and antiseptic solutions, antibiotic exposure and extremes of temperatures9,10. The glycocalyx polysaccharide capsule of the bacterium is an
important virulence determinant11.
The incubation period may range
from one day to many years. Symptoms appear two to four weeks after
exposure. The infection is classified
as acute, subacute, chronic, and
subclinical septicemia. Acute melioidosis is life threatening, accounting for up to 60% of all the infections of its kind. Mortality rate can
reach as high as 90% in the absence
of effective intervention, and 50%,
even after antibiotic therapy8.
Melioidosis can manifest as
localized infection, acute pulmonary infection, acute bloodstream
infection, or disseminated infection. Sub-clinical infections are also
observed. Localized infection manifests as an ulcer, nodule, or skin
abscess with associated fever and
myalgia and may progress rapidly
through the bloodstream. Mild
bronchitis to severe pneumonia is
the commonest presentation of pulmonary melioidosis which is chara-
cterized by high fever, headache,
anorexia, and myalgia. Chest pain is
common, but a nonproductive or
productive cough with normal sputum is the hallmark of this form of
melioidosis. Cavitary lesions on
chest X-ray resemble pulmonary
tuberculosis. Diabetes and renal insufficiency make patients vulnerable
for blood stream infection, which
usually results in septic shock. Symptoms include fever, headache, respiratory distress, abdominal discomfort, joint pain, muscle tenderness,
and disorientation. Disseminated
melioidosis may be acute or chronic
and presents with abscess formation
in various organs of the body, and
may or may not be associated with
sepsis. Liver, lung, spleen, prostate,
joints, bones, viscera, lymph nodes,
skin, or even brain may be affected.
Besides fever, patient may have
weight loss, stomach or chest pain,
muscle or joint pain, headache or
seizure12.
Current interventions are early
intravenous administration of antibiotics, ceftazidime or carbapenems, for 10 to 14 days, followed by
oral administration of co-trimoxazole or doxycycline for 3-6 months.
Although ceftazidime was reported
to be the most effective antibiotic for
melioidosis, its therapeutic response
is disappointingly slow in most
cases, probably because its efficacy
is multifactorial and dependent on
the properties of the organism and the clinical symptoms and immune status of the host . Carbapenem, the
MIC of which was found to be relatively low in an in
vitro experiment10, is currently considered a preferred
antibiotic. This, combined with one or more other antibiotics, yield a better therapeutic outcome. Melioidosis
in India has been reported in a child by Raghavan et al in
199113. A series of 28 patients of septicemic melioidosis
over 10 years has been reported from Vellore14.
Major risk factors for contracting this disease are
diabetes, liver disease, renal disease, thalassemia,
cancer or other immune-suppressing conditions not
related to HIV, chronic lung disease (such as cystic
fibrosis, chronic obstructive pulmonary disease, and
bronchiectasis)15. We had the rare opportunity to cure a
39 year old male patient who had been referred to our
tertiary care centre at Kochi, due to septicemia caused
by Burkholderia pseudomallei infection.
CASE REPORT
A 39-year-old male farmer hailing from Kozhenchery
(Pathanamthitta district), a place inundated by the rivers
Manimala and Pamba, was admitted on February 2012,
at a Medical College hospital (Thiruvalla) with 5 days
history of fever, chills, rigors and painful inflammation
of left ankle and elbow joints. He was on regular treatment for type 2 diabetes mellitus, systemic hypertension and dyslipidemia, for the last 8 years. He was in
the habit of consuming around 90-150 ml of alcohol per
day for the last 10 years, which he stopped 25 days prior
to hospitalization. Upon admission in the local hospital,
he was conscious, febrile, tachycardic, normotensive
and lab reports showed TC 14400/ ESR 131/ Hemoglobin 10.9/ Creatinine 0.86/ SGOT 109/SGPT 165/ALP
512/ fT4 17.21. He was provisionally diagnosed to have
septic arthritis and treatment was initiated with intra
articular aminoglycoside injection after sending the
blood and joint pus aspirate for culture & sensitivity.
Gram staining of joint aspirate revealed plenty of pus
cells and few GNB. Cultures, provisionally were suggestive of non-fermenting Gram negative bacilli suspicious of Burkholderia species sensitive to ceftazidime
and imipenem, but resistant to polymixin B. However,
there was no therapeutic efficacy and his symptoms of
fever and cough continued, chest X ray worsened and he
developed type 1 respiratory failure. Subsequently, he
was admitted in our Emergency room ICU at Kochi.
His vital signs upon arrival were: temperature 100
degree F; pulse 107 beats/min; respiratory rate 22
breaths/min; blood pressure 130/90 mmHg; peripheral
oxygen saturation 96%(on 2 litre O2 nasal prongs). He
was conscious, with coarse breathing sounds from both
lungs. ABG showed pH 7.513/pCO2 23.6/pO2 89.6/sO2 95.3/ lac 1.7/ HCO3- 19.1 on 2 litre O2 nasal
prongs. Abdominal examination was normal. The skin
overlying medial aspect of left ankle showed erythema
with diffuse tenderness around entire ankle joint with
mild restriction of movements. The left elbow dorsal
aspect had a minor swelling with associated painful
restriction of elbow movements. The patient denied a
history of trauma, but had a habit of walking barefoot in
his farm. He had never been to any South East Asian
countries or Australia in his lifetime.
The subsequent laboratory tests performed showed :
white blood cells, 17x109/L; ratio of neutrophils to
white blood cells 85.9%; ESR 60 mm/h; C-reactive
protein 261.6 mg/L; Albumin 2.12; Globulin 3.6;
Serum Creatinine 0.65; Serum Urea 20.6. A chest
radiograph showed minimal infiltrates in bilateral hilar
areas (Figure 1) .
Fig 1
Ultrasound scan showed hepatomegaly with mild
coarsening of echotexture with splenomegaly and
cholelithiasis. Transthoracic echocardiography revealed a good left ventricular systolic and diastolic
function and 50% of ejection fraction with no RWMA,
valves normal, no effusion/clot. Aerobic & anaerobic
blood culture samples were sent to lab for analysis. Left
elbow and ankle synovial fluid was sent for culture and
sensitivity after performing arthrotomy & drainage
(under regional block) in Feb 2012. After admission, the
following diagnoses were made: (I) Septic arthritis
(II) Early pneumonia (III) Melioidosis. Subsequently i.v
vancomycin, i.v piperacillin sodium USP and tazobactam sodium combination, doxycycline tablets & i.v
clindamycin were initiated and later on the antibiotic
regime were changed to imipenem i.v, clindamycin i.v,
ceftazidime i.v, vancomycin i.v and trimethoprim
160mg+ sulfamethoxazole 800mg combination
double strength tablets. Sugars were managed with
insulin according to sliding scale.
Fig 2
35
Escape From Disseminated Melioidosis Of Tropics: A Case Report And Literature Review
Serum latex agglutination test for rheumatoid factor
was negative. His aerobic blood culture came out to be
positive for Gram-negative bacterium Burkholderia
pseudomallei (Figure 2), which was subsequently
confirmed in the ankle and elbow synovial fluid culture
reports in late Feb 2012 .
DISCUSSION
Literature review showed a predominance of
meloidosis cases in southern coastal belts of India, but
very few cases were reported from Kerala.
Our patient was diabetic, which can be compared
with the study done by Vidyalaxmi et al which showed
The bacterium showed sensitivity to imipenem,
76% correlation of Melioidosis with diabetes mellitus17.
ceftazidime, chloramphenicol, cotrimoxazole, tigecyPatient was an alcohol consumer and was also incidcline and doxycycline. From day eight onwards, patient
entally detected to have features suggestive of chronic
remained afebrile, joint pains subsided and he imliver disease in abdominal ultrasonography. Alcohol
proved symptomatically, blood counts normalized,
consumption is yet another proven risk factor for
CRP decreased and he was shifted to ward. With
melioidosis. Bone involvement in our subject was also
adequate physiotherapy, joint mobility dramatically
favourable to a diagnosis of melioidosis as it has been
improved and he was discharged from the hospital on
earlier reported by Morse LP et al18. Septic arthritis cases
March 2012 with Inj. Imipenem 2 g iv BD, Inj. Ceftasimilar to our subject, reported from Mangalore during
zidime 2 g iv BD and Trimethoprim 160mg+ Sulfa2005-2006, have ended up in 100% mortality16. There
methoxazole 800mg combination double strength
could be several possible factors that might have
tablets 2 tablets thrice daily, all for a week and was
salvaged our patient's life. First, the causative Burksubsequently followed up for next 6 months with no
holderia pseudomallei was detected at a very early
relapse.
stage. Second, timely administration of appropriate
antibiotics and initiation of early
TABLE 1 : Review of cases in India
goal directed therapy for sepsis.
Clinical presentation
Year
Outcome
Place
Treatment
Ceftazidime i.v was initiated as per
globally
proven studies along with
Ceftazidime &
1996
Tamil Nadu
Fever with insulin dependent DM
Treated
carbapenem, that might have
cotrimoxazole
improved the overall prognosis of
28 patients, 30 isolates from blood,
Tamil Nadu
2003
the patient, which has earlier been
Ceftazidime&
Death
8 from pus, 3 from synovial fluid,
Cotrimoxazole
confirmed by Cheng et al9. Third,
2 from sputum
prompt and early surgical debrideTreated
ment of the joints removed one foci
Septicemia
Imipenem
2003 Hyderabad
of sepsis. Fourth, apart from a mild
Death
25 cases
2005- Mangalore
Ceftazidime &
degree
of liver dysfunction (prob2006
cotrimoxazole for
3 septic arthritis with DM
ably secondary to chronic alcoholic
6 months
2 supraclavicular mass with DM
liver disease), other systems were
1 pericardial effusion with DM
not affected, and he never went into
1 scalp abscess with DM
septic shock, which might have
2 psoas abscess with DM
contributed to his early recovery.
16
2 gluteal abscess with interstitial lung
disease and COPD on steroids
Based on overall data, we suspect
that the septicemia caused by acute
septicemic melioidosis in this victim
might have been triggered by the
invasion of Burkholderia pseudomallei through water borne routes,
as he had a habit of walking barefoot
in his farm and also was actively
involved in cattle breeding and agricultural activities.
5 pneumonia
3 renal disease with DM and chronic
renal failure
1 pancreatic pseudocyst with alcoholic
liver disease
1 pneumonia/septic arthritis with DM
3 PUO with malnutrition
1 pneumonia without septicemia with
DM
2007
Tamil Nadu
Genitourinary infection with DM type 1
Genitourinary infection with DM type 2
Death
2007
Tamil Nadu
Liver abscess- 2 cases
Ceftazidime &
cotrimoxazole
Treated
2008
Pondicherry
Diabetes with splenic abscess & foot
abscess
Ceftazidime
Treated
Tamil Nadu
2009
36
Treatment could
not be started
Pondicherry
HIV positive
Ceftazidime &
cotrimoxazole
Pre-term neonate
Meropenem
Treated
CONCLUSION
The medical community should
be highly alert to the possibility of
melioidosis in areas where the B.
Pseudomallei is endemic. It may
resemble TB clinically and radiologically. Therefore, B. pseudomallei
has been called the 'great mimicker'
of other infectious diseases such as
TB, syphilis and typhoid fever19-22. Careful investigations
into the patient's history of exposure to polluted water or
soil, and early bacterial examination of clinical samples
are crucial for correct and timely diagnosis. Persons with
exposed skin wounds with risk factors like diabetes,
alcohol consumption or chronic renal disease are at
increased risk for melioidosis, and should avoid direct
contact with soil, excreta and standing water. Those
performing agricultural activities should wear boots to
prevent infection through the feet and lower legs.
Standard contact precautions (like mask, gloves, and
gown) should be used by healthcare workers to prevent
infection.
At the same time, once diagnosed, timely administration of effective antibiotics and adequate fluid
resuscitation to counteract hypovolemia at the early
stage of therapy also help to save life. Eradication of the
organism following infection is difficult, with a slow
fever-clearance time, the need for prolonged antibiotic
therapy and a high rate of relapse, if therapy is not
completed. Mortality from melioidosis septic shock
remains high despite appropriate antimicrobial therapy.
The vast paddy fields and monsoons with heavy rains13
and waterlogged areas of Kerala serve as an ideal habitat
for B.pseudomallei. The diagnosis of melioidosis requires clinical vigilance and an intensive microbiological
support. By presenting this rare case, we hope to raise
the awareness of clinicians to the existence of melioidosis in India. Presently, no effective vaccine is
available against B. pseudomallei infection. Current
approaches under evaluation include conjugate DNA,
attenuated and heterologous vaccines, attenuated
mutants with invasive capacity having reduced ability to
produce a fatal infection23. Before recommending
prophylactic measures, studies to identify the prevalence of the etiological organism in the environment
are urgently warranted24. Prevention of disease and a
reduction in mortality and the rate of relapse are the
priority areas for future research studies.
Acknowledgements
All the staff of Department of Emergency Medicine,
Amrita Institute Of Medical Sciences (Kochi), India.
References
1. Whitmore A, Krishnaswami CS (1912) An account of the discovery
of a hitherto undescribed infective disease occurring among the
population of Rangoon. Indian Med Gaz 47: 262–7.
2. Jain V, Jain D, Kataria H, et al. (2007) Melioidosis: A review of
orthopedic manifestations, clinical features, diagnosis and management. Indian Journal of Medical Sciences 61: 580.
3. Dance DA (1991) Melioidosis: the tip of the iceberg? Clin Microbiol
Rev 4: 52–60.
4. Chaowagul W, White NJ, Dance DAB, et al. (1989) Melioidosis: A
Major Cause of Community-Acquired Septicemia in Northeastern
Thailand. J Infect Dis 159: 890–9.
5. Leelarasamee A, Bovornkitti S (1989) Melioidosis: Review and
Update. Clin Infect Dis 11: 413–25.
6. Pibalpakdee P, Wongratanacheewin S, Taweechaisupapong S, et
al. (2012) Diffusion and activity of antibiotics against Burkholderia
pseudomallei biofilms. International Journal of Antimicrobial Agents
39: 356–9.
7. Currie B , Anstey N (2015) Treatment and prognosis of melioidosis
http://www.uptodate.com/contents/treatment-and-prognosis-ofmelioidosis.
8. Jin J-L, Ning Y-X (2014) Septicemic melioidosis: a case report and
literature review. J Thorac Dis 6: E1–E4.
9. Cheng AC, Currie BJ (2005) Melioidosis: epidemiology, pathophysiology, and management. Clin Microbiol Rev 18: 383–416.
10. White NJ (2003) Melioidosis. The Lancet 361: 1715–22.
11. Steinmetz I, Rohde M, Brenneke B (1995) Purification and
characterization of an exopolysaccharide of Burkholderia (Pseudomonas) pseudomallei. Infect Immun 63: 3959–65.
12. CDC - Symptoms - Melioidosis (n.d.). Available: http://www.cdc.gov/melioidosis/symptoms/. Accessed 25 March 2015.
13. Saravu K, Mukhopadhyay C, Vishwanath S, et al. (2010) Melioidosis in southern India: epidemiological and clinical profile.
Southeast Asian J Trop Med Public Health 41: 407.
14. Saravu K, Mukhopadhyay C, Vishwanath S, et al. (2010) Melioidosis in southern India: epidemiological and clinical profile.
Southeast Asian J Trop Med Public Health 41: 404.
15. CDC - Information for Health Care Workers - Melioidosis (n.d.).
Available: http://www.cdc.gov/melioidosis/health-care-workers/.
Accessed 25 March 2015.
16. Barman P, Sidhwa H, Shirkhande PA (2011) Melioidosis: A Case
Report. J Glob Infect Dis 3: 183–6.
17. Vidyalakshmi K, Shrikala B, Bharathi B, et al. (2007) Melioidosis:
an under-diagnosed entity in western coastal India: a clinicomicrobiological analysis. Indian J Med Microbiol 25: 245–8.
18. Morse LP, Smith J, Mehta J, et al. (2013) Osteomyelitis and septic
arthritis from infection with Burkholderia pseudomallei: A 20-year
prospective melioidosis study from northern Australia. J Orthop 10:
86–91.
19. Kosuwon W, Saengnipanthkul S, Mahaisavariya B, et al.(1993)
Musculoskeletal melioidosis. J Bone Joint Surg Am 75: 1811–5.
20. Saengnipanthkul S, Laupattarakasem W, Kowsuwon W,et al.
(1991) Isolated articular melioidosis. Clin Orthop Relat Res: 182–5.
21. Sirikulchayanonta V, Subhadrabandhu T (1994) Melioidosis.
Another etiology of granulomatous osteomyelitis. Report of 2 cases.
Clin Orthop Relat Res: 183–6.
22. Wilairatana P, Wilairatana V (1994) Melioidotic spondylitis mimicking tuberculous spondylitis. Southeast Asian J Trop Med Public
Health 25: 603–4.
23. Warawa J, Woods DE (2002) Melioidosis vaccines. Expert Rev
Vaccines 1: 477–82.
24. Mukhopadhyay C, Chawla K, Krishna S, et al. (2008) Emergence
of Burkholderia pseudomallei and pandrug-resistant non-fermenters
from southern Karnataka, India. Trans R Soc Trop Med Hyg 102 Suppl
1: S12–S17.
37
Vol. 11, NO: 2
July - Dec 2015, Page 1 - 44
CASE REPORT
A Rare Case of Malignant Hyperthermia
*Shyam Sundar.P, **Suresh Kumar.R, **Anand Kumar.A
ABSTRACT
Malignant Hyperthermia (MH) is a rare disorder which is usually precipitated by inhalational anaesthetic agents and succinylcholine. We present a case of Malignant Hyperthermia that occurred in a young male patient. After induction with propofol and
succinylcholine, the patient had a cardiac event. There was an elevation in temperature and end-tidal carbon dioxide. His
creatinine kinase levels also were elevated significantly. The genetic testing for MH was inconclusive. There was response to
dantrolene, but the patient expired subsequently.
Keywords: Malignant hyperthermia, Succinylcholine, Dantrolene, Genetic Testing.
INTRODUCTION
Malignant Hyperthermia (MH) is a
rare disorder, especially in the Indian population. MH was first reported by Denborough and Lovell from
Australia in 1960. There are only
three cases1-3 of MH that have been
reported from India following
exposure to anaesthetic drugs. We
are reporting a case of MH that we
encountered.
CASE REPORT
Our patient was an 18 year old
boy scheduled to undergo removal
of implant of the olecranon process
in a peripheral hospital. The details
of the initial surgery, which was
done four years earlier for the fixation of the olecranon process, were
not available.
The patient was premedicated
with glycopyrrolate and morphine.
He was induced with propofol and
succinylcholine. Laryngeal mask
airway (LMA) was introduced and
anaesthesia was maintained with
isoflurane. The patient was placed
in the lateral decubitus position. At
this point of time, absence of peripheral pulse was noted. Hence the
patient was turned back to the
supine position and cardiopulmonary resuscitation (CPR) started.
During CPR, patient had to be defibrillated for ventricular fibrillation
(VF). After return of spontaneous
circulation (ROSC), the patient had
tachycardia. The LMA was removed when patient was breathing
normally an hour later. Ten minutes
Depts. of *Anaesthesiology & Critical Care
and **Neurology, AIMS, Kochi.
38
after this the patient developed respiratory distress. He was intubated
and ventilation maintained manually. There was worsening of tachycardia (~200/min). In spite of hyperventilation, the end tidal carbon dioxide concentration (ETCO2) was rising (> 55mmHg). A
rapid rise in temperature was noted
(39.5o C). The supportive measures
including cooling were continued
and the patient was transported to
our hospital.
106
250,000
104
104
102
101
101
100
100
2
3
4
98.6
99
5
6
7
161,980
150,000
100
99
98
244,240
239,470
200,000
103
1
nificant rise in the serum concentration of CPK. It reached a maximum of 244,240 IU on the 3rd postoperative day. Initially, he was maintaining a good urine output
(>100mL/h). However this dropped drastically. Hence, haemodialysis was initiated from 2nd postoperative day onwards. On the 3rd
postoperative day, parenteral Dantrolene Sodium was given. Subsequently, the CPK levels and body
temperature decreased.
8
9
Post op days
Fig. 1 - Body temperature
100,000
95,430
67,780
50,000
19,290
28,135
2,488
0
1
2
3
4
5
6
7
8
18,040
5,733
9
10
Post op days
On arrival here, the patient was
sedated, haemodynamically unstable and on ventilatory support.
There was rigidity of both upper and
lower limbs. Considering the possibility of MH, we hydrated him well
aiming at a urine output of 200–
300 mL/h. Other supportive measures were continued. As his temperature was rising, apart from
normal cooling measures, the Haemostat® (cooling device used for
cardiac surgery) was also used. The
initial blood analysis revealed a
serum creatinine of 1.7 mg/dL, potassium of 3.5 mmol/L, creatine
kinase (CPK) of 2488 IU, and blood
gas analysis showed a pH of 7.29,
PaCO2–47mmHg, HCO3– 19mmol/L. Subsequently, there was a sig-
Fig. 2 - Serum concentration of Creatine
Phosphokinase (CPK)
In spite of all these measures,
there was no improvement in the
patient's neurological or renal status. From the 4th postoperative day
onwards, the brainstem reflexes
were absent clinically. But all supportive measures were continued.
Haemodialysis was continued till
the 9th postoperative day, as he remained anuric. An EEG was done on
the 8th postoperative day, which
showed electro-cerebral silence. An
apnoea test was done on the 11th
postoperative day which was
positive for brain death. We continued the ventilatory support till his
cardiac death.
DISCUSSION
The three main differential diag-noses that we
considered were Neurolept Malignant Syndrome
(NMS), Hypoxic Ischaemic Encephalopathy (HIE) and
Malignant Hyperthermia (MH).
Rigidity and elevated levels of CPK can be seen in
NMS. However, he had not received any of the drugs
that precipitate NMS. Otherwise it is clinically difficult
to differentiate between MH and NMS as the symptoms
and signs in both these conditions can be very similar.
The patient had a cardiac arrest during induction. It
was a witnessed arrest in an operative theatre setting
under the careful observation of an anaesthetist and
hence the patient was resuscitated immediately. So the
possibility of HIE would be unlikely. Also such extreme
levels of CPK are unusual following a CPR. The hyperpyrexia also can't be explained solely based on HIE.
So our working diagnosis was that of MH. The specific treatment for MH is giving Dantrolene. Dantrolene
was not immediately available. We continued supportive care including good hydration, aggressive cooling
and haemodialysis. We preserved blood samples for
genetic studies. Caffeine Halothane contracture test
(CHCT) which is considered the gold standard for
diagnosing MH is not yet available in India, though
Saxena2 has reported the first ever CHCT from our
country.
We also graded our patient for MH based on the
clinical grading scale suggested by Larach4. A score of
more than 50 is almost certain of MH. Our patient's
score was 63. This confirmed our diagnosis of MH on
clinical grounds. The score is described in Table 1.
Table 1 - MH scoring of our patient
brainstem reflexes but later developed brainstem
dysfunction. This could probably be due to the uncontrolled hyperpyrexia during the initial 72 hours.
The genetic testing was done in the Division of
Molecular Genetics at the University of Pittsburgh
Medical Centre, USA with the help of our paediatric
geneticist. The patient's blood samples were sent for
analysis. The RYR gene hotspot screening studies were
done on the patient's samples. The screening did not
show any deleterious changes. So the test was
inconclusive for MH. The MHAUS5 guidelines for
testing for MH have suggested that absence of a
causative mutation does not rule out MH susceptibility.
MH is a rare genetic disorder that usually occurs
following exposure to inhalational anaesthetic agents
and/or succinylcholine. There are many case reports of
MH following anaesthetic exposure in the western
literature since the early 1960s'. However there are
only three reports of MH that have been published from
India. The general belief has been that the Indian
population is not predisposed to MH. Gupta PK and
Hopkins PM6 have described how the Indian population
could be susceptible to MH, contrary to what was
believed earlier. There are recent case reports of MH
from East Asian countries as well7. Thus, the Indian
population could be susceptible to MH. Anaesthesiologists need to have a high index of suspicion to
diagnose MH. In the absence of muscle testing facilities
and the problems with genetic testing, the clinical
grading scale4 is a useful tool to diagnose MH.
In our opinion, family members of patients with MH
should also be carefully screened before any surgery.
Hence asking for family history of immediate relatives
with minor anaesthetic complications or MH should be
done as a part of pre anaesthetic check up to avoid this
fatal complication.
CONCLUSION
Subsequently we managed to get Dantrolene and
the patient's temperature and CPK levels decreased
significantly afterwards. The patient initially had intact
We have reported a case of MH based on clinical and
laboratory parameters. The genetic test was inconclusive. MH is definitely a rare situation which an
anaesthetist may face once in his lifetime. The lesson
learnt from this case is that mortality in MH is high. In
our case, even though the CPK and other metabolic
parameters improved significantly after starting
dantrolene, there was a delay in initiation because of
non availability. We need to have centres where the
muscle biopsy and testing can be undertaken. Also we
would like to suggest setting up an MH registry in our
country so that in future, all suspected cases of MH can
be reported. Dantrolene sodium, which has helped to
decrease the mortality of this disorder to a great extent,
should be easily available to anaesthesiologists in India.
Maybe an MH hotline would probably help in
achieving this.
39
A Rare Case of Malignant Hyperthermia
ACKNOWLEDGEMENTS
Anaesth 2007; 51 (6): 534-5.
We thank Dr.Sheela Nampoothiri, head of Paediatric
Genetics, who helped us in doing the genetic testing.
We also thank the Division of Molecular Genetics at the
University of Pittsburgh Medical Centre for doing the
genetic testing.
3. Gopalakrishnan CV, Suparna B, Arun V. A rare case of malignant
hyperthermia in the Indian subcontinent. Anaesthesia 2010; 65:
1141-52.
4. Larach MG, Localio AR, Allen GC, et al. A clinical grading scale to
predict malignant hyperthermia susceptibility. Anesthesiology
1994; 80: 771-9.
References
5. http://www.mhaus.org (accessed 29/11/2012).
1.http://www.ispub.com/journal/the-internet-journal-of-pharmacology/volume-1-number-1/malignant-hyperthermia-in-theindian-subcontinent-non-availability-of-dantrolene-a-cause-forconcern-1.html (accessed 29/11/2012).
6. Gupta PK, Hopkins PM. Malignant Hyperthermia in India. Anaesthesia 2010; 65: 1059-68.
2. Saxena KN, Dua CK. Malignant Hyperthermia-A Case Report. Ind J
40
7. Wang YL, Luo AL, Tan G et al. Clinical features and diagnosis for
Chinese cases with malignant hyperthermia: a case cluster from
2005 to 2007. Chinese Medical Journal 2010; 123 (10): 1241-5.
Vol. 11, NO: 2
July - Dec 2015, Page 1 - 44
CASE REPORT
Inadvertent Insertion of Ryle's Tube into the Trachea
Following Endotracheal Intubation
Mohammed kutty K, Deepa Mirium Varghese,
Mathew George, Gokuldas Menon
ABSTRACT
Insertion of nasogastric tubes are done routinely and commonly but complications of this procedure are under-reported. The
traditional method of air insufflation and epigastric auscultation may not be a reliable indicator of gastric placement. It can very
well miss a malposition. Radiological evidence is the gold standard for correct placement, and the NG tube position should be
confirmed by an X-ray before any feeds are initiated through it. We report the case of a faulty insertion of NGT post-operatively on
table, which was detected later, and corrected before any complications ensued.
Key words: Nasogastric tube, malposition, pneumothorax, pleural effusion, epigastric insufflation, X-ray chest and abdomen.
CASE REPORT
Insertion of feeding tubes although widely considered to be easy is
not without complications, but the
problems are under-reported. The
rate of malposition of feeding tubes
into the trachea and distal airways
ranges from 2-2.5%. Sorokin &
Gottlieb reported 50 cases of nasogastric tube malposition into the
right or left bronchus out of 2000
tube insertions over a period of 4
yrs, with 2 mortalities.
We report the case of a 32 yr old
man, diagnosed as a case of
falcotentorial meningioma for occipital craniotomy and excision. He
had no comorbidities. All the preoperative blood and radiological investigations were within normal
limits. Craniotomy was panned
under GA with invasive arterial and
CVP monitoring. He had a standard
IV induction with vecuronium for
neuromuscular blockade. The patient was intubated with a cuffed oral
endotracheal tube of 8.5mm internal diameter fixed at 22cm. The
patient was connected to the
anaesthesia workstation and ventilated in volume control mode with
the following settings - FiO2 40%,
TV-450ml, RR 15bpm, FGF 2l. A 16
F ryles tube was inserted via the
right nostril. It went in without much
difficulty, fixed at 60cm mark on the
nose and its position was confirmed
by auscultation of epigastrium after
Dept. of Anaesthesiology (Neuro-Ortho Division) ,
AIMS, Kochi, Kerala.
insufflating air via the RT. The patient was positioned in a semi-prone
decubitus and the surgery proceeded uneventfully. Intra-operatively
it was noticed that the set tidal
volume of 450 ml was not getting
delivered, showing a leak of 100120 ml. There was a steady increase
in the end-tidal carbon dioxide
levels, which remained persistently
above 36 mm of Hg despite increasing the respiratory rate to 20/
minute. An examination for obvious circuit or cuff leak did not
reveal any gross leak and we
assumed that the anaesthesia
workstation had developed an error
in flow-meter calibration. Hence
the TV was increased to 600ml to
increase the minute ventilation,
despite which no rise in peak airway pressures were noted. There
were no episodes of desaturation.
The rest of the surgery proceeded uneventfully and it was decided
to electively ventilate the patient
because of long duration of surgery
(nearly 15hrs). Patient was ventilated in the ICU in SIMV/PS mode
with FIO240%, TV 500 ml (delivering 380-400ml), RR-15/mt. Morning chest x-ray in the ICU revealed a
malpositioned RT, with its tip in the
right mainstem bronchus. The tracheal position was further proved
by demonstration of air bubbles
from RT when placed under water,
synchronous with breathing.
Fortunately for the patient there was
no pneumothorax or pleural effusion and we hadn't started any feeds
via NG tube.
The Ryles tube was removed
without any delay and the patient
was extubated within a few hrs once
he met the extubation criteria.The
rest of his ICU stay was uneventful
and he was shifted out of the ICU on
second postoperative day.
DISCUSSION
Failure to recognize a malpositioned feeding tube may lead to
serious injuries to the tracheobronchial pleural tract such as pneumothorax, pleural effusions and
even death. Intravascular penetration although rare is also mentioned
–erosion into the retroesophageal
aberrant right subclavian artery, right
internal jugular vein to right atrium.
Tube knotting and impaction, tube
breakage, enteric perforation, tube
double backing and kinking are a
few non-thoracic complications.
Thus this relatively easy procedure is not without complications.
Reporting such events will make the
clinicians aware about the potential
morbidity and mortality associated
with such a simple procedure often
done unsupervised by junior staff
and nurses. Further, this may lead to
formulation of a plan to contain this
problem, and thus enhance the
safety.
41
Inadvertent Insertion of Ryle's Tube into the Trachea Following Endotracheal Intubation
Below described are a few points to enhance the
chances of a successful nasogastric tube insertion1. The traditional air insufflation and epigastric
auscultation may not be a reliable indicator of
gastric placement, as good thoraco-abdominal
sound transmission can lead to misinterpretation.
An NG aspirate with pH <5 may not always be
from stomach – it could be from an infected pleural
or respiratory secretion.
2. The X-ray remains the gold standard to verify the
correct placement. The 2 step insertion is the best
way to prevent complications. Initial 30 cm is the
crucial damage limiting distance, as it is at the
trachea-esophageal transition zone. Verify the
position by an X-ray and introduce further to 50 cm
and confirm by a 2nd X-ray.
3. Insertion of excess tubing is to be avoided.
4. Tracheal entry can be detected using small, disposable capnometers.
5. Newer nasoendoscopes with guidewire exchange,
are very useful in difficult, prior failed or complicated attempts.
42
6. A few high risk groups are identified- Intubated and sedated
- elderly
- mentally obtunded
- following lung transplantation
-repeated attempts after earlier pulmonary
misadsventures.
Reference
1. Sorokin R,Gottlieb J E- Enhancing patient safety during feeding tube
insertion- a review of more than 2000 insertions. JPEN J Parenter
Enteral Nutr 2006;30:440-5[pubmed].
2. Sweta, Uma Srivastava, Archana Agarwal-Inadvertent insertion of
nasogastric tube into the trachea of a conscious patient IJCCM 2012
Apr- Jun 16(2):116-7.
3. Jain Bhaskara Pillai, Annette Vegas& Stephanie Brister- Thoracic
complications of NG tube: review of safe practice Oxford Journals>
Interactive Cardiovasc Thoracic, isSurgery> volume 4,issue 5>Pp
429-33.
4. Rassias A J, Ball P A, Corwin H L- A prospective study of tracheopulmonary complications associated with the placement of narrow
bore enteral feeding tubes Crit Care 1998; 2: 25-8 [ pubmed].
5. Thomas B, Cummin D, Falcone R E- Accidental pneumothorax
from a nasogastric tube N.Engl J Med 1996; 335: 1325[ pubmed].
Vol. 11, NO: 2
July - Dec 2015, Page 1 - 44
CASE REPORT
Titanium Elastic Nailing in Paediatric Fracture Femur
- A Case Report
S. Ravi Subramaniam, Krishnakumar.R
ABSTRACT
In a majority of patients of the paediatric age group who sustain a femur shaft fracture, the management is usually conservative with
the help of casting. However in some cases where the reduction cannot be maintained, a surgical intervention maybe required.
This is a case of a 5 year old boy with a shaft of femur fracture who was managed with the help of a titanium elastic nail. Post
operatively he was non weight bearing for 2 months. He started weight bearing after 2 months with no complications. The implant
was removed one year later. Titanium elastic nailing is a good and stable method of fixation of fracture shaft of femur in the
paediatric age group, with minimal complications.
INTRODUCTION
In a majority of pediatric patients,
femoral shaft fractures are managed
with closed reduction and casting.
But in some cases where the reduction cannot be maintained a surgical intervention may be required.
There are many complications seen
with other methods of fixation,
which can be avoided with titanium
elastic nailing, like infection and refracture . Titanium elastic nails have
become more popular in the fixation of femur shaft fractures in
children.
CASE REPORT
A 5 year old boy came to our
casualty with a history of fall from a
bike with direct injury to his right
thigh, after which he developed
pain and swelling over the right
thigh. He was unable to weight
bear. He had no external wounds.
He had no other injuries. His distal
pulses were well felt. X-ray of the
femur (Fig 1a and 1b) AP and Lateral
views were done which showed a
displaced fracture of the shaft of the
right femur, AO classification 31A2.
The patient was stabilized with
an above knee slab and was planned for a closed reduction and internal fixation with a titanium elastic
nail the next day (Fig 2).
Fig 4
Fig 2 - Intra-operatively-Pre reduction
Two 3mm Titanium elastic nails
were inserted through the entry
point which held the fracture in
place (Fig 5). The reduction was reconfirmed with the help of an image
intensifier. The haemostasis was checked and the wound was closed.
Pre-op X-ray
Fig 3 - Post reduction
During the procedure the fracture
was reduced and checked (Fig 3)
with the help of an image intensifier. A 4 cm incision was made
over the anteromedial and anterolateral aspect of distal femur.
Fib 1a
Fib 1b
Dept. of Orthopedics, AIMS, Kochi.
The entry point (Fig 4) was made
with the help of a drill bit above the
level of the femoral physis on both
sides.
Fig 5
The patient was kept non weight
bearing for 2 months following the
surgery.
X-rays showed good callus formation and healing at serial followups post operatively, with a well
united fracture of the right shaft of
femur with the TENS nail insitu. The
43
Titanium Elastic Nailing in Paediatric Fracture Femur - A Case Report
implant was removed under general anaesthesia after 1
year.
Fig 6
Post operative X-ray
Fib 7a
Fib 7b
creates six points of fixation to achieve biomechanical
stability.Elder nails act differently, through nail stacking
and from canal fill. Healing is by external callus as
titanium nails provide an elastic and stable fixation
which allows controlled motion at the site of fracture.
In our case, the fixation was done with the help of a
pair of TENS nails, as the fracture was unstable without
fixation. The reduction was good with a varus angle of
less than 3 degrees (upto 10 degrees is the acceptable
varus)1. The patient was kept non weight bearing for 2
months. Wound healing was good. The patient mobilized well post operatively. He did not complain of pain
post operatively over the nail entry site which has been
found to be the commonest complication post
operatively-11%2,5,6.
There were no ulcerations or bursa formation present. On follow up there was no proximal migration of
the nail.
Titanium nails give good elastic and stable fixation,
and allow healing by callus formation from controlled
movement at the fracture site. The use of a titanium
elastic nail in the fixation of the fracture helps avoid
complications like pin tract infections, non-union and
long term plaster application. There were no signs of
compartment syndrome7. It has also been proven that
the time of healing has been reduced with the use of
TENS nailing as opposed to other methods of fixation. It
is a closed method of fixation and has a low rate of
infection.
Fib 8a
Fib 8b
Post op X-ray- after implant removal.
CONCLUSION
TENS nailing provides good stability in young patients with fracture shaft of femur and is preferable over
other methods of fixation in the paediatric age group
due to the decreased rate of side effects.
References
1. Titanium elastic nails for pediatric tibial shaft fractures, J Child
Orthop. 2007 Nov; 1(5): 281–6.
2. Kubiak EN, Egol KA, Scher D, et al. (2005). Operative treatment of
tibial shaft fractures in children: are elastic stable intramedullary nails
an improvement over external fixation? J Bone Joint Surg Am
87:1761– 8 [PubMed].
3. Ligier JN, Metaizeau JP, Prevot J, et al. (1985). Elastic stable intramedullary pinning of long bone fractures in children. Z Kinderchir
40:209–12 [PubMed].
4. Flynn JM, Hresko T, Reynolds RA, et al. (2001). Titanium elastic
nails for pediatric femur fractures–a multicenter study of early results
with analysis of complications. J PediatrOrthop 21(1):4–8 [PubMed].
Fib 9a
Fib 9b
The patient is mobilizing well with no discomfort.
DISCUSSION
A Titanium elastic nail, acts like an internal splint
owing to the divergent “ C ” like configuration. This
44
5. Luhmann S, Schootman M, Schoenecker PL, et al. (2003). Complications of titanium elastic nails for pediatric femoral shaft fractures.
J PediatrOrthop 23:443–7 [PubMed].
6. Sink E, Gralla J, Repine M (2005). Complications of pediatric femur
fractures treated with titanium elastic nails: a comparison of fracture
types. J PediatrOrthop 25:577–80 [PubMed].
7. Goodwin RC, Gaynor T, Mahar A, et al. (2005). Intramedullary flexible nail fixation of unstable pediatric tibialdiaphyseal fractures.
J PediatrOrthop 25(4):570–6 [PubMed].