Maya Bhat

Isolated Cerebellitis in Scrub Typhus.

To the Editor: A 6-y-old girl presented to the emergency of a pediatric hospital with five day history of fever, difficulty in walking, slurring of speech of three day duration and one episode of generalized tonic-clonic seizures. On admission, the patient was afebrile and had enlarged cervical lymph nodes. Cerebrospinal fluid (CSF) analysis was normal. Neurological examination revealed scanning type of speech with positive cerebellar signs. The power in all the limbs was 4/5 with decreased tone. There were no meningeal signs. Blood examination revealed a total WBC count of 10, 500 cells/mm, an erythrocyte sedimentation rate of 25 mm/h and elevated C-reactive protein of 26.9 mg/L. CT scan of the brain performed on the eighth day of illness revealed effacement of the cerebellar folia with early hydrocephalus. Weil Felix test was positive, OXK titre of 1:320 was suggestive of scrub typhus. MRI of the brain revealed, diffuse increased signal intensity in the cerebellar cortex on T2 and FLAIR images, suggesting an inflammatory process confined to the cerebellum (Fig. 1). Furthermore, the cerebellar cortex appeared swollen, a finding consistent with diffuse cerebellitis. No enhancement was evident on post contrast scans. The central nervous system manifestations of scrub typhus range from aseptic meningitis to encephalomyelitis [1, 2]. Aseptic meningitis has been reported in about 11 % of patients with scrub typhus [1]. The authors attributed it to involvement of the small vessels in the brain [3]. Others have proposed an

Giant melanocytic nevi with neurocutaneous melanosis masquerading as neurofibromas.

Neurocutaneous melanosis is congenital melanocytic nevus with neurological manifestations. We report a 4-year-old female child presenting with hyperpigmented and nodular skin lesion associated with developmental delay and convulsions. The child had multiple brownish-black nevi on the face and chest and giant melanocytic nevi on thoraco-abdomen, back, and gluteal region. Computed tomography scan of the brain showed calcification in the pons, right cerebellar hemisphere, and left medial temporal lobe. Skin biopsy done from nodular hyperpigmented site was suggestive of melanocytic nevi. Electroencephalogram showed multifocal epileptiform discharges.

Novel imaging findings in two cases of biotinidase deficiency-a treatable metabolic disorder

Biotinidase deficiency is one of the few treatable inborn errors of metabolism. We describe unique MRI features in two patients with biotinidase deficiency. Brain MRI in case one demonstrated symmetrical diffusion restriction in bilateral hippocampi, parahippocampal gyri, central tegmental tracts, and cerebellar white matter besides other structures that have been reported previously. The second patient was noted to have bilateral symmetrical T2 hyperintensities involving the anterior, lateral and posterior columns of the entire spinal cord on MRI. Knowledge of the varied MRI features of biotinidase deficiency will aid the prompt diagnosis and treatment of a potentially disabling illness, especially in countries where newborn screening is not routinely performed.

Ohtahara syndrome associated with hemimegalencephaly and intracranial lipoma

Hemimegalencephaly is a disorder of cortical malformation and is associated with various disorders including various neurocutaneous syndromes and many seizure types. We present a case of hemimegalencephaly associated with Ohtahara syndrome and intracranial and facial lipoma.

Diffusion restriction in ethylmalonic encephalopathy – An imaging evidence of the pathophysiology of the disease

Ethylmalonic encephalopathy is an inborn error of metabolism characterized by encephalopathy, petechiae chronic diarrhea and acrocyanosis. Imaging findings include patchy signal changes in the basal ganglia, periaqueductal region, subcortical white matter and cerebellum. We describe the novel finding of diffusion restriction in brain lesions, in a proven case of ethylmalonic encephalopathy.

Tay-Sachs Disease Presenting as Refractory Epilepsy with Autistic Regression Secondary to a Novel Mutation in HEXA Gene

To the Editor: Tay-Sachs disease (TSD) is an autosomal recessive lysosomal storage disorder due to deficiency of beta hexosaminidase A enzyme. It is caused by mutations in HEXA gene [1]. The prevalence of TSD in general population is 1 in 3,20,000 [2]. We report a child with TSD presenting as autistic regression and refractory epilepsy due to novel mutation. A 3-y-old boy born out of s degree consanguineous marriage with normal birth history, presented with loss of attained social and language milestones following febrile episode. Patient subsequently developed myoclonic jerks. On examination, normal head size, no hepatosplenomegaly and no cherry red spot were found. On investigations, complete blood count, liver function, renal function, serum ammonia, serum lactate, arterial blood gases were normal. MRI brain showed hypointensity in bilateral thalamus (Fig. 1a) and peri-ventricular white matter signal changes (Fig. 1b). EEG was suggestive of diffuse slowing. Tandem mass spectrometry and urine for abnormal metabolites was normal. Leukocyte enzyme analysis for hexosaminidase Awas low [1.5 (normal 62–310)]. HEXA gene analysis revealed a novel homozygous missense mutation c. 1219G > T (p.V407F) in exon11. Parental testing reveled a heterozygous missense mutation on HEXA gene. Myoclonic jerks partially controlled with anti-epileptic drugs. The child succumbed to his illness at the age of 5 y due to aspiration pneumonia. Prenatal genetic testing for next pregnancy is advised. In the current case, the possible differential diagnosis considered were, Neuronal ceroid lipofuscinosis (NCL), Lafora body disease, mitochondrial disorders and gangliosidosis. Enzyme assay for NCL1 and 2 were normal. Axillary skin biopsy for negative inclusion bodies ruled out Lafora body disease. Mitochondrial disorders were ruled out as serum lactate and tandem mass spectrometry was normal. Enzyme assay showed deficiency of Beta Hexosaminidase A level; hence diagnosed as TSD. The usual presentation of TSD is developmental delay followed by regression in the later part of the infancy. Examination usually shows large head with cherry red spot in the fundus. In this child regression started after 3 y of age predominantly the social interaction with refractory epilepsy, normal head size and without cherry red spot. There are more than 130 mutations identified in the HEXA gene [2]. This phenotype has not been described previously in the literature. In the genetic testing, the novel mutation was found. In conclusion TSD should be considered as a differential diagnosis in a patient who present as autistic regression with epilepsy. * Vykuntaraju K. Gowda drknvraju@hotmail.com; drknvraju@yahoo.co.in

Sandhoff disease without hepatosplenomegaly due to hexosaminidase B gene mutation

Sandhoff disease is a neurodegenerative disease caused due to deficiency of hexosaminidase (HEX) A and B. A 1-year-old male child presented with regression of milestones, exaggerated startle response, decreased vision, and seizures from 6 months of age. The child had coarse facies without hepatosplenomegaly. Serum levels of β hexosaminidase total (A + B) were low. Genetic testing for Sandhoff disease revealed a homozygous missense variant on HEXB gene. The case is presented to highlight that the absence of hepatosplenomegaly should not restrain in suspecting Sandhoff disease.

A case of Canavan disease with microcephaly

BACKGROUND Canavan disease is an autosomal recessive disorder with spongy degeneration of white matter of the brain. It presents with developmental delay, visual problems and macrocephaly. PATIENT DESCRIPTION We report a ten-month old boy with Canavan disease who presented with global developmental delay, seizures, abnormal eye movements and microcephaly. RESULTS MRI brain revealed diffuse involvement of the supra tentorial white matter, globus pallidi, thalami, dentate nuclei and brainstem with sparing of the corpus callosum. The genetic testing revealed homozygous mutation of aspartoacylase gene [c.859 G>A (p.Ala287Thr)] in Exon 6. CONCLUSION Possibility of Canavan disease should be considered even in the presence of microcephaly.

Unusual Imaging Findings in Brain and Spinal Cord in Two Siblings With Maple Syrup Urine Disease

Maple syrup urine disease (MSUD) is a rare metabolic disease affecting the neural tissue. While the brain abnormalities present on MRI are well known, spinal imaging features have not been studied. We herewith report an unusual finding of enlarged Virchow Robin spaces in brain and novel spinal cord changes in two biochemically diagnosed cases of MSUD. To the best of our knowledge, spinal MRI findings in cases of MSUD have not been previously reported. Knowledge of spinal MRI findings may be useful in diagnosis of this rare disorder.

Liquid chromatography-tandem mass spectrometry method for estimation of a panel of lysophosphatidylcholines in dried blood spots for screening of X-linked adrenoleukodystrophy

BACKGROUND Elevated C26:0-lysophosphatidylcholine (LPC) is used as a biomarker to screen newborns for X-linked adrenoleukodystrophy (X-ALD), an inherited peroxisomal disorder. Our aim was to develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based assay for estimating a panel of LPCs (C20:0, C22:0, C24:0 and C26:0) from dried blood spots (DBS) and to evaluate its sensitivity and specificity for identification of X-ALD in clinically suspected cases. METHODS LPCs (C20:0 - C26:0) were extracted from 3.2 mm DBS, spiked with an isotopically labelled internal standard (C26:0-d4-LPC) in a 96-well plate, and measured by LC-MS/MS in electrospray ionization positive, multiple reaction monitoring mode. The sensitivity and specificity of the method was evaluated in 21 patients diagnosed with X-ALD and 375 healthy controls. RESULTS Elevated C26:0 and C24:0-LPCs were 100% sensitive and specific for identification of X-ALD. The sensitivity and specificity of elevated C26:0/C20:0, C26/C22:0, C24:0/C20:0 and C24/C22:0-LPCs were > 80% and 70%, respectively. CONCLUSION The LC-MS/MS method for estimating LPCs in DBS can be used to identify X-ALD in clinically suspected patients. Further large-scale studies to determine the pre-analytical variables and to define age- and gender-specific reference ranges in various ethnic groups are warranted before introducing this method for high-risk screening in India.