Key-words:
Dandy-Walker variant - hydrocephalus - neurocutaneous melanosis - tuberculous meningitis
Introduction
Neurocutaneous melanosis (NCM) is one of the rare phakomatoses. NCM is a childhood
disorder which has varied presentations and is associated with other Neurocutaneous
syndromes like Sturge-Weber syndrome, Neurofibromatosis type 1, Dandy-Walker syndrome.
The prognosis of NCM is dismal, more so when it presented in adults and associated
with Dandy-Walker syndrome, like our case.
Case Report
A 28-year-old male patient presented with history of repeated episodes of convulsion
for over a year, and altered sensorium, headache, vomiting and diminished vision since
a month prior to his admission. He was initially treated elsewhere with broad spectrum
antibiotics and anticonvulsants. On evaluation at Emergency, his heart rate was 114/min,
blood pressure was 154/110 mm of Hg, Glasgow Coma Score was E4V1M5, and pupils were
sluggishly reacting to light. Fundoscopy showed bilateral post-papilloedema optic
atrophy. His vision could not be assessed properly. On general examination, he was
found to have congenital giant cutaneous hairy melanocytic nevus over trunk in “bathing
suit” distribution associated with multiple hairy satellite cutaneous nevi over the
rest of the body [[Figure 1]]a,[[Figure 1]]b,[[Figure 1]]c,[[Figure 1]]d,[[Figure 1]]e. There was no family history of similar skin lesion.
Figure 1: (a-e) Congenital giant cutaneous hairy melanocytic nevus over trunk in “bathing suit”
distribution associated with multiple hairy satellite cutaneous nevi over the rest
of the body
Contrast-enhanced computerized tomography (CECT) of brain revealed dural based hyperdense
lesions in both frontal lobes with diffuse leptomeningeal thickening and enhancement,
communicating hydrocephalus with posterior fossa cyst and partial agenesis of cerebellar
vermis [[Figure 2]]. Lumbar cerebrospinal fluid (CSF) examination showed xanthochromia, very high protein
(749.4 mg %), cell count of 16 with lymphocytes of 56%, normal sugar and elevated
adenosine deaminase (ADA) of 20.18. Liver function tests were deranged with more than
300 of all hepatic enzymes and mild elevation of bilirubin. He was also found to be
hypothyroid (T3-0.79 ng/ml, T4-6.63 ug/dL, and thyroid stimulating hormone - 6.77
uIU/ml). CECT of chest and abdomen were normal.
Figure 2: Contrast enhanced computerized tomography of brain revealed dural based hyperdense
lesions in both frontal lobes with diffuse leptomeningeal thickening and enhancement,
communicating hydrocephalus with posterior fossa cyst and partial agenesis of cerebellar
vermis
Based on CSF study, modified anti-tubercular drugs (ATD) started along with dexamethasone
and broad-spectrum antibiotics (injection meropenem and injection amikacin, both having
some anti-tubercular actions). His sensorium improved. MRI of brain with contrast
subsequently showed lesions which were cortical based and showed T1W and T2W hyper-intensity
were enhancing with contrast along with extensive leptomeningeal enhancement, obstructive
hydrocephalus and a large posterior fossa extra-axial cyst, communicating with the
4th ventricle [[Figure 3]]a,[[Figure 3]]b,[[Figure 3]]c. MRI of spine showed multiple extramedullary intra-dural septations and loculations
in the dorsal spine and thickened cauda equine nerve roots [[Figure 4]]a and [[Figure 4]]b. A Ventriculo-Peritoneal shunt (VP shunt) was done after a week of the above treatment.
Ventricular CSF showed protein of 98 mg%, 6 cells and ADA of 1.54. Acid Fast Bacillus
was not found in the smear. Gene Xpert for MTB/RIF from CSF did not detect tubercle
bacilli. CSF cytology from cytocentrifuge deposit showing atypical melanocytes with
brown pigment and vesicular nuclei with prominent eosinophilic nucleoli. Cell block
from CSF centrifuged deposit showed many cells with vesicular nuclei having prominent
nucleoli and brown pigment [[Figure 5]]a and [[Figure 5]]b. Presence of melanocytes confirmed by immunohistochemicalstains specific melanocytes
HMB45 and Melan A which target proteins gp100 and Melan A on the cells.
Figure 3: (a) MRI of brain showing linear cortical based (b) T1 hyperintense and (c) T2 hypointense
signal in bilateral cerebral hemisphere showing no obvious enhancement or any other
abnormal enhancing focus in post contrast
Figure 4: MRI of spine showing (a) T1 hyperintense and (b) T2 hypointense linear extramedullary
intradural septations and loculations in the dorsal spine and thickened cauda equina
nerve roots.
Figure 5: (a) cerebrospinal fluid cytology from cytocentrifuge deposit showing atypical melanocytes
with brown pigment and vesicular nuclei with prominent eosinophilic nucleoli. (b)
Cell block from cerebrospinal fluid centrifuged deposit showed many cells with vesicular
nuclei having prominent nucleoli and brown pigment
Discussion
NCM is a rare, congenital, noninheritable disorder characterized by the presence of
multiple and or large congenital melanocytic nevi and are associated with benign and
or malignant melanocytic tumors of the leptomeninges.[[1]] First case of NCM was described and reported by Rokitansky in 1861 in 14 years
old boy with a congenital nevus and mental retardation and hydrocephalus.[[2]] Since then over 300 cases have been reported in literature.[[3]] Most cases are sporadic, with an equal gender predilection and they usually present
before the age of 2 years.[[4]],[[5]],[[6]] Rarely NCM presents in adulthood. Some remain asymptomatic.[[7]]
Pathogenesis of NCM has been stated as a neuro-ectodermal defect during morphogenesis
involving melanoblasts of skin and pia mater originating from neural crest cells.
Two-thirds of patients of NCM have giant congenital melanocytic nevus. A third shows
multiple small lesions. Our case had features of both.
Clinical presentations are usually with signs of intracranial hypertension, focal
seizures, motor deficits or aphasia. Hydrocephalus is present in two-thirds of patients
due to obstruction of CSF flow or reduced absorption as a result of thickened leptomeninges.
NCM has been reported to be associated with other neuro-cutaneous syndromes such as
Sturge-Weber Syndrome and von Recklinghausen's neurofibromatosis 1. NCM has also been
reported to be associated with posterior fossa cystic malformations like Dandy Walker
malformation (DWM), like in our case, in about 10% cases.[[8]],[[9]],[[10]] The prognosis of patients of NCM with DWM is extremely poor. Children die early
in life from malignant transformation of the melanosis. NCM and DWM concurrence also
suggests common etio-pathogenesis. There are case reports of NCM masquerading as neurofibromas.[[11]] NCM with multiple intracranial calcifications are also described in literature.
The diagnostic criteria were first given by Fox[[12]] in 1972, and later modified by Kadonaga and Frieden[[13]] in 1991, which were as follows: (1) large nevus (>20 cm in adults and lesions which
are approximately 9 cm of diameter on the head or 6 cm on the body in infants), (2)
multiple (≥3) nevi, (3) no evidence of cutaneous melanoma, except in cases where meningeal
lesions are histologically benign, (4) no evidence of meningeal melanoma, except in
cases where the cutaneous lesions are benign. Our case was compatible with the diagnosis
of NCM (large nevus, multiple nevi, no evidence of cutaneous or meningeal melanoma).
The treatment with radiation therapy or chemotherapy is dismal if there is the benign
melanocytic proliferation of the leptomeninges. Patients of NCM may develop malignant
melanoma in 40%–60% of cases, and malignant transformation is heralded by development
of intra-parenchymal invasion or intracranial or intraspinal masses.[[14]]
Increased CSF ADA level is an important diagnostic clue in tubercular meningitis (TBM).
It has sensitivity of 82.14% and specificity of 90.91% in diagnosing TBM.[[15]] Raised CSF ADA level has been reported in cryptococcal meningitis,[[16]] listeria meningitis,[[17]] sarcoid meningitis,[[18]] meningeal involvement with leukemia or lymphoma,[[19]] toxoplasmosis, cerebral infarction, neurosyphilis, and other aseptic meningitis.
Among these, TBM has highest ADA activities (median 21.3 U/l, range 20.0–23.0), followed
by lymphoma (median 13.0, range 4.0–25.0). The sensitivity and specificity of the
test for diagnosing TBM is 100% and 99% respectively when a cut-off value of 20.0
is used. In our case, as the CSF ADA as well as the protein was very high and suggestive
of TBM and after a week of treatment with ATD and steroids, both values came down
significantly, we proposed a full course of ATD (12 months).
We may also postulate that the high ADA and high CSF protein are associated with NCM
because of the CSF flow obstruction by the melanin pigments which could have been
resolved so quickly with Dexamethasone rather than associated TBM (in the absence
of tubercle bacillus isolation). However, there are no such references in the available
literature. We tend to regularly follow-up the patient regarding the neurological
outcome as well as cutaneous lesions at 3–6 months interval.
Conclusion
Our case is unique because of adult presentation, with giant as well as multiple nevi,
extensive intracerebral and spinal cord involvement, hydrocephalus, Dandy-Walker Variant
complicated by possible TBM.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms.
In the form, the patient has given his consent for his images and other clinical information
to be reported in the journal. The patient understand that name and initials will
not be published and due efforts will be made to conceal identity, but anonymity cannot
be guaranteed.
