MRI Changes in Patients with Incontinentia pigmenti

MRI Changes in Patients with Incontinentia pigmenti
Poster No.:
C-1530
Congress:
ECR 2012
Type:
Educational Exhibit
Authors:
E. Golgor, G. Hahn; Dresden/DE
Keywords:
Seizure disorders, Genetic defects, Contrast agent-intravenous,
MR-Diffusion/Perfusion, MR, Neuroradiology brain
DOI:
10.1594/ecr2012/C-1530
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Page 1 of 16
Learning objectives
1.
2.
To reveal the disease pattern of Incontinentia pigmenti.
To demonstrate the MRI findings in our patient population.
Background
Incontinentia pigmenti (IP or Bloch-Sulzberger-Syndrome) is a rare, X-linked,
neuroectodermal disorder with a reported prevalence of 1:40 000 [1]. Most sufferers are
female [1], as there is high in-utero mortality of affected males.
First described by Garod in 1906 the disease name stems from histological melanin
deposits seen in the superficial dermis (supposedly "incontinence" of melanin from the
deep dermis) [2].
The primary cause of IP relates to mutations of the NEMO gene (NF-kappa-B essential
modulator) located on Xq28 [3]. Disturbance of the NF-kappa-B pathway makes IP
cells highly sensitive to apoptosis and impairs cellular adhesion as well as immune and
inflammatory responses [4].
The high variable clinical manifestations of IP in affected persons include abnormalities
of skin, eyes, hair, teeth and the central nervous system (CNS). An erythematous and
vesicular rash along the lines of Blaschko in the perinatal period is characteristic (Fig. 1
on page 2). Approximately thirty percent of IP patients show CNS involvement [5],
manifesting as seizures, developmental delay and spastic cerebral palsy. In newborns,
early onset of seizures is an important sign suggesting IP.
The pathogenesis of neurological involvement is not well understood. However, findings
accordable with cerebral infarction or necrosis [6, 7] support the theory that vascular
disease may play an important role.
Images for this section:
Page 2 of 16
Page 3 of 16
Fig. 1: Vesicular (a) and erythematous (b) skin lesions along the lines of Blaschko
characteristic for the initial IP manifestation. The images were kindly provided by PD
Dr. J. Dinger from Department for Neonatology and Pediatric Intensive Care, Children's
Clinic of the University Hospital Carl Gustav Carus, Dresden, Germany.
Page 4 of 16
Imaging findings OR Procedure details
We reviewed neuroimaging studies obtained on 0.5 T and 1.5 T MRI scanners of four
patients - three infants between the ages of 2-3 weeks, and one 20 year old - diagnosed
or followed up at our institution in the last 10 years. In two cases, diffusion tensor imaging
(DWI) was performed.
All patients were female, had a history of neonatal seizures beginning within their first
five days of life, as well as typical vesicular skin lesions which appeared soon after birth.
In one patient, MRI, performed three weeks after birth, revealed wedged-shaped cortical
lesions, isointense to cerebrospinal fluid, extending into the subcortical white matter
bilaterally, (Fig. 2 on page 6).
MRI of the other two neonates was performed in the first and second week after birth. The
findings in these two patients consisted of scattered blotchy lesions in the basal ganglia,
the deep white matter and subcortical white matter bilaterally.
On T2-weighted images these lesions were inhomogeneous, focally hyperintense (Fig.
3 on page 6), and almost invisible (Fig. 4 on page 7) as a result of physiologic
marginal myelination.
On T1-weighted images the lesions demonstrated either faint hyperintensity (Fig. 5 on
page 8) or were hypointense with slight signal hyperintensity at the margin (Fig. 6 on
page 9). Application of contrast medium revealed considerable lesion enhancement
in one case (Fig. 7 on page 10) but no enhancement in the other case.
On susceptibility weighted images (SWI) the lesions were partly hemorrhagic (Fig. 8 on
page 11).
DWI exposed multiple patchy areas of significantly reduced water diffusion in the
subcortical and periventricular white matter as well as the basal ganglia (Fig. 9 on page
12).
The MRI of the adult patient demonstrated microcephaly, cerebral and corpus callosum
atrophy (Fig. 10 on page 13) as well as extensive white matter demyelination (Fig.
11 on page 14).
Page 5 of 16
Images for this section:
Fig. 2: Sagittal T1w MRI showing wedged-shaped regions, isointense to cerebral spinal
fluid, with involvement of subcortical white matter
Page 6 of 16
Fig. 3: Axial T2w MRI image showing patchy predominantly hyperintense lesion of the
right basal ganglia
Page 7 of 16
Fig. 4: Axial T2w MRI image showing predominant hypointense lesions in the left frontal
white matter
Page 8 of 16
Fig. 5: Axial T1w MRI image of the same patient as in Fig. 3 revealing faint hyperintense
lesions localized to the left frontal white matter
Page 9 of 16
Fig. 6: Axial T1w MRI image of the same patient as in Fig. 2 demonstrating scattered,
predominantly hypointense lesions with a slightly hyperintense signal at the border,
localized to the subcortical white matter
Page 10 of 16
Fig. 7: Parasagittal T1w MRI image after application of contrast agent showing enhancing
areas in the deep and subcortical white matter
Page 11 of 16
Fig. 8: MRI SWI image demonstrating punctuate haemorrhage in the left subcortical white
matter corresponding to the lesion seen in Fig. 5
Page 12 of 16
Fig. 9: MRI DWI (a) of the same patient as in Figs. 2, 5, 7 showing patchy high signal
changes in the supratentorial frontal and parietal white matter bilaterally, particularly in
the periventricular white matter and right basal ganglia with corresponding MR ADC map
(b) demonstrating low signal in the same areas confirming restrictive diffusion
Page 13 of 16
Fig. 10: Coronal (a) and sagittal (b) T1w MRI images of a 20 year old female IP patient
revealing cerebral atrophy, microcephaly and hypoplasia of the corpus callosum
Fig. 11: Axial T2w (a) and FLAIR (b) MRI images of the same patient as in Fig. 9 showing
large lateral ventrikels with hyperintense periventricular signal
Page 14 of 16
Conclusion
The initial brain abnormalities on MRI of neonates with CNS manifestation of IP are
consistent.
We observed patchy lesions of periventricular and subcortical white matter in all of our
patients. In one case the basal ganglia were also involved. The signal changes on the T1-,
T2-, and contrast enhanced images varied between patients, most likely as a result of the
different timings of the examinations. However, DWI revealed the entire extent of brain
damage by exposing the presence of multiple lesions with significantly reduced water
diffusion. These findings support the hypothesis that cytotoxic edema is characteristic for
the acute, infarction-like CNS lesions of patients with IP.
In contrast, the brain changes in an adult patient were non-specific, showing cerebral and
corpus callosum atrophy and expanded demyelination of white matter similar to what can
be seen in periventricular leukomalacia.
IP should be included in the differential diagnosis in cases of neonatal seizures with
characteristic skin lesions, especially in female patients, as its presentation can mimic
encephalopathy of hypoxic-ischemic or viral origin.
Personal Information
References
1. Carney, R. G. (1976) Incontinentia pigmenti. A world statistical analysis. Arch Dermatol
112(4): 535-542.
2. Garrod, A. E. (1906) Peculiar pigmentation of the skin in an infant. Trans Clin Soc
London 39: 216-217.
3. Fusco F., Bardaro T., Fimiani G., Mercadante V,. Miano M. G., Falco G., Israel A.,
Courtois G., D'Urso M., Ursini M.V. (2004) Molecular analysis of the genetic defect in a
large cohort of IP patients and identification of novel NEMO mutations interfering with
NF-kappaB activation. Hum Mol Genet 13(16): 1763-1773.
4. Sebban H., Coutrois G. (2006) NFkB and inflammation in genetic disease. Biochem
Pharmacol 72: 1153-1160.
Page 15 of 16
5. Landy S. J., Donnai D. (1993) Incontinentia pigmenti (Bloch-Sulzberger syndrome). J
Med Genet 30: 53-59.
6. Shah S. N., Gibbs S., Upton C. J,. Pickworth F. E., Garioh J. J. (2003) Incontinentia
pigmenti associated with cerebral palsy and cerebral leukomalacia: a case report and
literature review. Pediatr Dermatol 20(6): 491-494.
7. Wolf N. I., Kramer N., Harting I., Seitz A,. Ebinger F., Poschl J,. Rating D. (2005)
Diffuse cortical necrosis in a neonate with incontinentia pigmenti and an encephalitis-like
presentation. AJNR Am J Neuroradiol 26(6): 1580-1582.
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