Shrinivas Desai

Indian-Subcontinent NBIA: Unusual Phenotypes, Novel PANK2 Mutations, and Undetermined Genetic Forms

Neurodegeneration with brain iron accumulation (NBIA) is etiologically, clinically, and by imaging a heterogeneous group including NBIA types 1 [pantothenate kinase‐associated neurodegeneration (PKAN)] and 2 (PLA2G6‐associated neurodegeneration), neuroferritinopathy, and aceruloplasminaemia. Data on genetically defined Indian‐subcontinent NBIA cases are limited. We report 6 patients from the Indian‐subcontinent with a movement disorder and MRI basal ganglia iron deposition, compatible with diagnosis of an NBIA syndrome. All patients were screened for abnormalities in serum ceruloplasmin and ferritin levels and mutations in NBIA‐associated genes [pantothenate kinase 2 (PANK2), PLA2G6 and ferritin light chain (exon 4)]. We present clinical, imaging and genetic data correlating phenotype–genotype relations. Four patients carried PANK2 mutations, two of these were novel. The clinical phenotype was mainly dystonic with generalized dystonia and marked orobulbar features in the 4 adolescent‐onset cases. One of the four had a late‐onset (age 37) unilateral jerky postural tremor. His mutation, c.1379C>T, appears associated with a milder phenotype. Interestingly, he developed the eye‐of‐the‐tiger sign only 10 years after onset. Two of the six presented with adult‐onset levodopa (L‐dopa)‐responsive asymmetric re‐emergent rest tremor, developing L‐dopa‐induced dyskinesias, and good benefit to deep brain stimulation (in one), thus resembling Parkinsons disease (PD). Both had an eye‐of‐the‐tiger sign on MRI but were negative for known NBIA‐associated genes, suggesting the existence of further genetic or sporadic forms of NBIA syndromes. In conclusion, genetically determined NBIA cases from the Indian subcontinent suggest presence of unusual phenotypes of PANK2 and novel mutations. The phenotype of NBIA of unknown cause includes a PD‐like presentation.

Biotinidase deficiency: a reversible metabolic encephalopathy. Neuroimaging and MR spectroscopic findings in a series of four patients

BackgroundBiotinidase deficiency is a metabolic disorder characterized by inability to recycle biotin with resultant delayed myelination. Clinical findings include seizures, ataxia, alopecia and dermatitis with atypical findings of myoclonic jerks, neuropathy and spastic paraparesis. Neuroradiological findings include cerebral atrophy, encephalopathy and widened extracerebral CSF spaces. Many of the clinical and neuroradiological features are reversible except sensorineural hearing loss and optic atrophy.ObjectiveTo understand and describe the neuroimaging and spectroscopic findings of biotinidase deficiency.Materials and methodsWe evaluated the spectrum of neuroimaging and spectroscopic findings in four patients with biotinidase deficiency with follow-up studies in three patients.ResultsThe imaging findings were encephalopathy, low cerebral volume, ventriculomegaly and widened extracerebral CSF spaces. Uncommon findings were caudate involvement, parieto-occipital cortical abnormalities and one patient with restricted diffusion. Two patients had subdural effusions, which is uncommon in biotinidase deficiency. 1H-MR spectroscopy revealed elevated lactate, reversal of the choline/creatine ratio and decreased NAA peaks. Follow-up studies revealed complete reversal of imaging findings in two patients. ConclusionBiotinidase deficiency is a reversible metabolic encephalopathy. This study highlights the importance of early and prompt cliniconeuroradiological diagnosis of biotinidase deficiency as it has an extremely good clinical outcome if treatment is initiated from early infancy.

Reversible Parkinsonism and T1W pallidal hyperintensities in acute liver failure

We report on a young woman who survived acute liver failure (ALF) without liver transplant. During the ALF, she developed a disabling, levodopa‐unresponsive, symmetrical Parkinsonism. This was characterized by severe bradykinesia, mild rigidity, mutism, and prominent gait impairment. Magnetic resonance imaging (MRI) showed bilateral T1W pallidal hyperintensities. Parkinsonism and MRI changes remitted in parallel with normalization of hepatic function. We implicate excessive pallidal manganese deposition secondary to ALF in the pathogenesis of this neuroradiological syndrome. Though hitherto unreported, we propose that Parkinsonism with T1W pallidal hyperintensities may not be uncommon in ALF.

Non-infantile variant of desmoplastic ganglioglioma: a report of 2 cases

Desmoplastic infantile gangliogliomas (DIGs) are uncommon supratentorial brain tumors with a usually good prognosis despite an aggressive radiological appearance. These tumors form part of a spectrum of desmoplastic infantile tumors that includes desmoplastic infantile astrocytomas. DIGs are classified as benign WHO grade I tumors of infancy. Non-infantile variants of this biologically benign intracranial neoplasm are rare, with only four previous case reports in the literature. We report two cases of non-infantile DIG diagnosed at our institution on the basis of clinical features, radiological appearance and histological findings.

Menkes Kinky Hair Syndrome: A Rare Neurodegenerative Disease

Menkes kinky hair disease is a rare X-linked recessive disease nearly exclusively affecting males who present at 2-3 months of age due to abnormal functioning of copper-dependent enzymes due to deficiency of copper. Here, we describe a completely worked-up case of a 4-month-old male infant with very typical history and radiological features confirmed by biochemical and trichoanalysis. The initially seen asymmetric cortical and subcortical T2 hyperintensities in cerebral and cerebellar hemispheres converted into symmetrical diffuse cerebral and predominantly cerebellar atrophy with uniform loss of both white and grey matter on follow-up MRI. Also, subdural hemorrhages of various sizes and different stages and tortuosity of larger proximal intracranial vessels with distal narrowing were identified. Ours is a completely worked-up proven case of Menkes kinky hair disease (MKHD) with history, electroencephalography, biochemical, trichoanalysis, and MRI findings. This is a good teaching case and shows importance of clinical examination and biochemistry as complimentary to MRI. Tortuous intracranial arteries with blocked major vessels are found only in this disease, thus stressing the value of MR Angiography in these patients.

Magnetic Resonance-guided Focused Ultrasound Treatment for Uterine Fibroids: First Study in Indian Women

Objectives: To study the results of magnetic resonance-guided focused ultrasound surgery (MRgFUS) treatment carried out on Indian patients in our Hospital. Materials and Methods: Fifty Indian women (mean age = 36.2 ± 8.3 years) were treated for fibroids as outpatients using the ExAblate MRgFUS system (InSightec). Non-perfused volumes (NPVs) were measured immediately after treatment to calculate the treatment outcomes. A validated symptom-specific questionnaire to record their symptoms prior to treatment and six months following treatment was completed by patients. The size of the fibroids was measured on the day of the treatment and during the 6-month checkup to calculate shrinkage. Adverse events during and following treatment were recorded and monitored. Results: The average NPV ratio measured after the treatment was 88% ± 6%, indicative of high ablated fibroid tissue. Prior to treatment, the mean Symptoms Severity Score was 56.9 ± 4.8 (n = 50), which is indicative of highly symptomatic patients. Six months following treatment, there was an average fibroid shrinkage of 30% ± 11%, and a significant decrease in the mean score to 28.6 ± 6.0 (n = 50) (P < 0.001). There were no reports of serious or unexpected adverse events at any point during treatment or during the follow-up period from any of the 50 women treated in the current study. Conclusions: The current results obtained after 6 months of treatment corroborated previous data on the safety and efficacy of MRgFUS for treating uterine fibroids. This is the first publication that provides such data for a large cohort of Indian women.

Camptodactyly-Arthropathy-Coxa Vara-Pericarditis Syndrome: Important Differential for Juvenile Idiopathic Arthritis

Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome is an inherited disorder characterized by congenital or early-onset flexion camptodactyly, childhood-onset of non-inflammatory arthropathy, often associated with non-inflammatory pericarditis or pericardial effusion and progressive coxa vara. The causative gene is located on chromosome band 1q25-31. This gene encodes for “proteoglycan-4” (PRG-4), which is a surface lubricant for joints and tendons. This syndrome has distinct radiological and histological features, which are important to recognize since it may clinically mimic juvenile idiopathic arthritis and mutation studies may not be easily available. We describe a case of a 3-year 3-month-old female with features of CACP syndrome.

Multiple Cranial Nerve Enhancement: Uncommon Imaging Finding in Early Infantile Krabbe's Disease

Multiple cranial nerve enhancement in early infantile Krabbes disease is an uncommon imaging finding. We present an 8‐month‐old infant with early infantile Krabbes disease with enhancement of multiple cranial nerves and optic nerve hypertrophy.