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Objective: Medulloblastoma (MB) is a heterogenous tumor, and the prognosis is influenced by various clinical, histological, and molecular factors. The aim of the study is to determine the clinical profile and radiologic characteristics among the histo-molecular subgroups, the predictors of surgical outcome, and the pattern of relapse in pediatric and adult MB. Method: An analysis of 118 patients of MB who underwent surgical treatment at National Institute of Mental Health and Neurosciences, India, over a 7-year period (2005–2011) is presented. The clinical profile, radiologic characteristics, surgical nuances, and survival patterns are discussed. The relevant statistical analysis was done using SPSS software, version 22.0. Results: The mean age of the cohort was 12 years (12.3 ± 8.7). The primary manifestation was raised intracranial tension headache in 53 patients (44.9%), which was the predominant symptom in large cell/anaplastic (LCA)- and WNT-activated subgroups. The median preoperative Karnofsky performance score was 60 (60.6 ± 12.9). Vermian and hemispheric location of tumor was most commonly observed in non-WNT/non-SHH (groups 3 and 4; 91.7%) and SHH-activated (42.9%) subgroups, respectively. Ninety-two patients (78%) underwent preoperative ventriculoperitoneal shunts (VPS) for obstructive hydrocephalus (HCP) and 14 patients (11.8%) underwent VPS in the postoperative period. The median overall survival (OS) for the whole group was 82.1 ± 5.7 months and the median recurrence-free survival was 51.0 ± 4.8 months. While radiotherapy had a significant influence on OS, progression-free survival was influenced by radiotherapy as well as chemotherapy in both pediatric and adult cohort. Desmoplastic/nodular subtype and WNT-activated subgroup had the best prognosis; LCA and non-WNT/non-SHH had the worst prognosis. Conclusions: Majority of the patients were pediatric in the study. Age, hemispheric location of tumor, extent of resection, and adjuvant treatment status were the important clinical prognostic factors for survival. Surgery for MB is formidable, and VPS can be considered in persistent symptomatic and progressive HCP. Our study on pediatric and adult MB validates the prognostic significance of various clinical, radiologic, and histo-molecular parameters of MB.

Purpose Transcranial surgery(TCS) for pituitary adenoma(PA) is mostly reserved for lesions with widespread extensions. We sought to analyse the intraoperative challenges, morbidity and the factors associated with morbidity of transcranial approaches, in a large series from a tertiary neurosurgical institute. Methods We retrospectively evaluated 137 patients who underwent TCS for PA in our institute. The details of their clinical features, imaging, operative and peri-operative events and complications were collected and analysed. The factors associated with morbidity were evaluated. Results The mean age of the cohort was 40.86 ± 13.35 years. 21 (15.3%) patients developed significant post-operative hematoma, out of which 7 patients (5.1%) required re-exploration. Post-operative diabetes insipidus was noted in 45 patients (32.84%), while SIADH was noted in 10 patients (7.35%). Other complications were cranial nerve palsy in 14 patients (10.2%), visual deterioration in 7 patients (5.1%). Neither tumour characteristics nor the choice of approach was associated with occurrence of post op hematoma. SIADH was significantly associated with patients with tumours involving cavernous sinus (p = 0.019) and subfrontal extension (p = 0.031). Patients with post-operative hematoma had significantly higher incidence of post-op DI (57.1% vs 28.7%; p = 0.021), while similar correlation was not noticed with SIADH (4.7 vs 7.8%). Conclusion TCS plays a distinct, albeit a small role in surgical management of pituitary adenoma. Tumour related or approach related factors are not significantly associated with the incidence of hematoma. Post-operative hematoma significantly influences the incidence of DI. A proper and judicious selection of approach and meticulous surgical technique should result in a reduction in associated morbidity and mortality.

Ethylmalonic encephalopathy (EE; OMIM #602473) is an autosomal recessive disorder characterized by (1) progressive neurologic impairment, including global developmental delay with periods of regression during illness, progressive pyramidal and extrapyramidal signs, and seizures; and (2) generalized microvascular damage, including petechial purpura and chronic hemorrhagic diarrhea. It leads to premature death. EE is caused by mutations in ethylmalonic encephalopathy protein 1 ( ETHE1 ), and more than 60 different mutations have been reported.1,2 ETHE1 encodes a mitochondrial sulfur dioxygenase involved in the catabolism of hydrogen sulfide (H2S).2 Impairment of sulfur dioxygenase leads to the accumulation of hydrogen sulfide and its derivatives (thiosulphate) in various body fluids and tissues. Higher concentration of H2S is toxic and induces direct damage to cell membranes. It inhibits cytochrome c oxidase (COX), increases lactic acid and short-chain acyl-COA dehydrogenase, and leads to elevation of ethyl malonate and C4/C5 acylcarnitine in muscle and brain.2 We describe the clinical phenotype and MRI, pathologic, and biochemical findings of a patient with EE from India who had a novel homozygous c.493 G>C (p.D165H) variation in ETHE1 .

Objectives Studies exploring the outcome of epilepsy in patients with mitochondrial disorders are limited. This study examined the outcome of epilepsy in patients with mitochondrial disorders and its relation with the clinical phenotype, genotype and magnetic resonance imaging findings. Patients and methods The cohort was derived from the database of 67 patients with definite genetic diagnosis of mitochondrial disorders evaluated over a period of 11years (2006–2016). Among this, 27 had epilepsy and were included in final analysis. Data were analyzed with special reference to clinical phenotypes, genotypes, epilepsy characteristics, EEG findings, anti epileptic drugs used, therapeutic response, and magnetic resonance imaging findings. Patients were divided into three groups according to the seizure frequency at the time of last follow up: Group I- Seizure free; Group II- Infrequent seizures; Group III- uncontrolled seizures. For each group the clinical phenotype, genotype, magnetic resonance imaging and duration of epilepsy were compared. Results The phenotypes & genotypes included Mitochondrial Encephalopathy Lactic Acidosis and Stroke like episodes (MELAS) & m.3243A>G mutation (n = 10), Myoclonic Epilepsy Ragged Red Fiber syndrome (MERRF) & m.8344A>G mutation (n = 4), Chronic Progressive External Ophthalmoplegia plus & POLG1 mutation (CPEO, n = 6), episodic neuroregression due to nuclear mutations (n = 6; NDUFV1 (n = 3), NDUFA1, NDUFS2, MPV17-1 one each), and one patient with infantile basal ganglia stroke syndrome, mineralizing angiopathy & MT-ND5 mutations. Seven patients (25.9%) were seizure free; seven had infrequent seizures (25.9%), while thirteen (48.1%) had frequent uncontrolled seizures. Majority of the subjects in seizure free group had episodic neuroregression & leukoencephalopathy due to nuclear mutations (85.7%). Patients in group II with infrequent seizures had CPEO, POLG1 mutation and a normal MRI (71%) while 62% of the subjects in group III had MELAS, m.3243A>G mutation and stroke like lesions on MRI. Conclusions A fair correlation exists between the outcome of epilepsy, clinical phenotypes, genotypes and magnetic resonance imaging findings in patients with mitochondrial disorders. The recognition of these patterns is important clinically because of the therapeutic and prognostic implications.

Mutations in the mitochondrial-encoded nicotinamide adenine dinucleotide dehydrogenase 5 gene ( MT-ND5 ) has been implicated as an important genetic cause of childhood mitochondrial encephalomyopathies. This study reports the clinical and magnetic resonance imaging findings in two pediatric patients with mutations in the ND5 gene of mitochondrial DNA. The 8-month-old boy with m.13513 G > A mutation presented with infantile basal ganglia stroke syndrome secondary to mineralizing angiopathy. The 7-year-old girl with the m.13514A > G mutation had episodic regression, progressive ataxia, optic atrophy, and hyperactivity. Magnetic resonance imaging of the brain showed bilateral symmetrical signal intensity changes in the thalamus, tectal plate, and inferior olivary nucleus, which subsided on follow-up image. Both the patients had a stable course. Familiarity with the various phenotypic and magnetic resonance imaging findings and the clinical course in childhood mitochondrial encephalomyopathies may help the physician in targeted metabolic–genetic testing and prognostication.

Systemic complications following liquid glue embolisation of intracranial pial arteriovenous fistulae (AVF) are uncommonly reported. We report a patient who had a pulmonary embolism of a liquid glue during endovascular treatment of a pial AVF. The patient had haemodynamic instability, pulmonary hypertension, increased alveolar dead space and increased brain natriuretic peptide levels. In addition to other supportive measures, her pulmonary hypertension was controlled with sildenafil. Ten months after the event, the patient had a considerable improvement of the clinical and laboratory variables and a significant radiographic resolution of the glue from the pulmonary circulation.

Background: Mutation in the SURF1 is one of the most common nuclear mutations associated with Leigh syndrome and cytochrome c oxidase deficiency. This study aims to describe the phenotypic and imaging features in four patients with Leigh syndrome and novel SURF1 mutation. Methods: The study included four patients with Leigh syndrome and SURF1 mutations identified from a cohort of 25 children with Leigh syndrome seen over a period of six years (2006–2012). All the patients underwent a detailed neurological assessment, muscle biopsy, and sequencing of the complete mitochondrial genome and SURF1. Results: Three patients had classical presentation of Leigh syndrome. The fourth patient had a later age of onset with ataxia as the presenting manifestation and a stable course. Hypertrichosis, facial dysmorphism and hypopigmentation were the additional phenotypic features noted. On magnetic resonance imaging all patients had brainstem and cerebellar involvement and two had basal ganglia involvement in addition. The bilateral symmetrical hypertrophic olivary degeneration in these patients was striking. The SURF1 analysis identified previously unreported mutations in all the patients. On follow-up three patients expired and one had a stable course. Conclusions: Patients with Leigh syndrome and SURF1 mutation often have skin and hair abnormalities. Bilateral symmetrical hypertrophic olivary degeneration was a consistent finding on magnetic resonance imaging in these patients.

Background: Pediatric thoracolumbar (TL) spinal injuries are uncommon entities with an incidence of 5–34% of all pediatric spinal injuries. There is a scarcity of studies done on the pediatric population in the developing countries like India. This study aims to review our experience with TL spine injuries in children over a 12-year period. Materials and Methods: We retrospectively reviewed the epidemiology, risk factors, mechanisms, patterns of injury and management of pediatric TL injuries in our population. Results: There were 90 children with TL spine injuries comprising 2% of all the spine injuries treated in our institute. The mean age was 15.9 ± 3.2 years (range: 2–18 years) with a male predominance (3:1). The most common mode of injury was fall from height. 64/90 (71.1%) children sustained injury due to fall from height, 18/90 (20%) children sustained injury following motor vehicle accident and rest of the children sustained injury due to the fall of a heavy object over the neck. Most of the patients (27.8%) sustained Grade A injury. Lumbar spine was the most common spinal level injured (53.3%), and fractures were the most common type of injury (93.3%). Surgical fixation was performed in 18/90 (20%) children. Follow-up was available for 21 children of which 13 (62%) were ambulant at follow-up. Conclusion: TL injuries are rare and are most common in children older than 10 years and mainly involve the lumbar region. When indicated, surgical fusion of the involved vertebrae is safe and effective.

Reports on magnetic resonance imaging findings in patients with short chain acyl –Coenzyme A dehydrogenase (SCAD) deficiency, an autosomal recessive disorder caused by mutations in the acyl-Coenzyme A dehydrogenase (ACADS), are limited. Many asymptomatic carriers of ACAD variants have also been described necessitating careful evaluation of clinical and biochemical findings for an accurate diagnosis. Here we report a an infant with short chain acyl –Coenzyme A dehydrogenase (SCAD) deficiency diagnosed based on the characteristic biochemical findings and confirmed by genetic testing. He presented with refractory seizures and neuro regression at 4 months of age. His metabolic work up revealed elevated butyryl carnitine in plasma and ethyl malonic acid in urine. Magnetic resonance imaging of the brain showed cortical and basal ganglia signal changes with cortical swelling. Serial scans showed progression of the lesions resulting in cystic leukomalacia with brain atrophy. Exome sequencing revealed a novel homozygous nonsense variation, c.1146C > G (p.Y382Ter) in exon ten of ACADS which was further validated by Sanger sequencing. Both parents were heterozygous carriers. Follow up at 15 months showed gross psychomotor retardation and refractory seizures despite being on optimal doses of anti-epileptic medications, carnitine and multivitamin supplementation. This report expands the phenotypic and genotypic spectrum of SCAD deficiency.

Background Complications after gamma knife radiosurgery (GKRS) have been attributed most commonly to radiation-induced damage to the brain. Early occlusion of the draining veins has been postulated as one of the rare causes of complications after GKRS, which often occurs at or beyond 6 months after GKRS. Clinical Presentation We present a very rare incidence of acute onset of hemiparesis caused by a draining vein occlusion within 24 hours after GKRS for arteriovenous malformation. The patient developed hemiparesis within one day after GKRS, which partially improved with steroids. Radiologic investigations revealed an early occlusion of a draining vein, resulting in occlusive hyperemia and neurologic deficit. Conclusion Early draining vein occlusion is an important cause of postradiosurgery complications, and it can rarely occur within days.

Huppke -Brendel syndrome is a new addition to the evolving spectrum of copper metabolism defects. It is an autosomal recessive disorder characterized by congenital cataract, impaired hearing, and developmental delay with low copper and ceruloplasmin. It is caused by defects in SLC33A1 that codes for acetyl CoA transporter protein. Reports on variation in this gene causing human disease is extremely scarce and the metabolic link between this gene and copper metabolism is yet to be identified. Here we report a seven months old infant with Huppke-Brendel Syndrome. In addition to the already reported features, he also had hypo pigmented hair and hypogonadism. His magnetic resonance imaging revealed hypo myelination and cerebellar hypoplasia. Clinical exome sequencing revealed a homozygous two base pair deletion, c.542_543delTG (p.Val181GlyfsTer6) in exon 1 of the SLC33A1. This report expands the phenotypic and genotypic spectrum of Huppke Brendel syndrome.

Deficiency of gamma-amino-butyrate aminotransferase (ABAT) is a rare inherited disorder. A six-month-old girl presented with hyper-somnolence, hyperkinetic movements of distal extremities during wakefulness, hypotonia, bi-pyramidal signs, and impaired response to sound and visual stimuli. Brain MRI at five months showed restricted diffusion along the internal capsule and genu of corpus callosum. A follow up MRI at 18months, showed hyperintensities in brainstem, external and internal capsule, 'trilaminated' appearance of posterior limb of internal capsule and dysmyelination of sub-cortical white matter. MRS showed a peak between 2.2ppm and 2.4ppm, corresponding to glutamine, glutamate and GABA. EEG was normal at six months but showed multifocal epileptiform discharges at 18months. Targeted exome sequencing revealed compound heterozygous missense variations in ABAT resulting in its reduced function. We report the novel association of hypersomnolence and hyperkinetic movement disorder with ABAT variations thus expanding the clinical spectrum of this uncommon neuro-metabolic disorder and discuss the emerging role of GABA in pathways regulating sleep-wake cycle and movement disorders.

Objectives Reports of audiological manifestations in specific subgroups of mitochondrial disorders are limited. This study aims to describe the audiological findings in patients with MELAS syndrome and m.3243A>G mutation. Patients & methods Audiological evaluation was carried out in eight patients with confirmed MELAS syndrome and m.3243A>G mutation. The evaluation included a complete neurological evaluation, pure tone audiometry (n = 8), otoacoustic emissions (n = 8) and brainstem evoked response audiometry (n = 6), magnetic resonance imaging (n = 8) and muscle biospy (n = 6). Results Eight patients (Age range: 5–45 years; M:F-1:3) including six children and two adults underwent formal audiological evaluation. Five patients had hearing loss; of these two had “subclinical hearing loss”, one had moderate and two had severe hearing loss. The abnormalities included abnormal audiometry (n = 5), otoacoustic emission testing (n = 7) and absent brainstem auditory evoked responses (n = 1). The findings were suggestive of cochlear involvement in four and retrocochlear in one. Conclusions This study shows that hearing loss of both cochlear and retrocochlear origin occurs in patients with MELAS and may be subclinical. Early referrals for audiological evaluation is warranted to recognize the subclinical hearing loss in these patients. The therapeutic implications include early interventions in the form of hearing aids, cochlear implants and cautioning the physicians for avoidance of aminoglycosides.

Background: Stereotactic biopsy of brainstem lesions have been performed with varying indications, with most of the literature reporting on children. Materials and Methods: The present study retrospectively analyzed all cases that underwent stereotactic biopsy for brainstem lesion in both adult and pediatric population between 1994 and 2009 in a single tertiary neurosurgical center. The clinical and radiological features, technique of the procedure, morbidity, diagnostic accuracy, spectrum of diagnosis, and variations in adult and pediatric population were analyzed. Results: Eighty-two patients were included in the study. Computed tomography (CT) was used as guidance in 73 (38 children and 35 adults) patients and magnetic resonance imaging (MRI) in 9 (3 children and 6 adults). The biopsy was performed in a procedure room under local anesthesia in most adults, while children required sedation. Glioblastoma comprised 29.3% of all pathologies in children, compared with only 4.9% of the pathologies in adult population (P = 0.007). Tuberculosis was the next major diagnosis (9.8%). In 12 patients, initial biopsy was inconclusive. Following a repeat biopsy in 5 of these patients, a diagnosis was possible for 75/82 (91.5%) patients by STB. The location of the target, the choice of entry, the radiological characteristic of the lesion, enhancement pattern, and age group did not significantly correlate with the occurrence of inconclusive biopsy. Permanent complications occurred in two patients (2.4%). There was no mortality in this series. Conclusion: Stereotactic biopsy has an important role in brainstem lesions, more significantly in adults, due to wider pathological spectrum. It can be performed safely under local anesthesia through a twist drill craniostomy in most of the adults.

Background: Epidemiology of primary central nervous system lymphoma (PCNSL) world-wide shows an increase in incidence linked to human immunodeficiency virus (HIV) pandemic. Materials and Methods: This retrospective review of case records analyzed the trends of hospital-based incidence of PCNSL over two decades (1991-2010), relation to immune status and effect of steroids on yield of stereotactic biopsy (STB). Results: A total of 76 cases of PCNSL were diagnosed over a period of two decades. Incidence of lymphomas amongst all biopsied lesions showed a gradual increase from 0.18% at the beginning of study period to 0.41% at the end of study period. Only 8.6% (3 of 35 tested) of the PCNSL patients were positive for HIV. The mean age of patients with HIV infection (31.3 ± 3.5 years) was significantly lower compared with those without HIV infection (44.7 ± 10.9 years) (P = 0.033). Diagnosis was obtained by open biopsy in 32 patients (42.1%) and STB in 44 patients (57.9%). Open biopsy yielded a histological confirmation of PCNSL in all cases. Among those who underwent STB, the incidence of negative biopsy with short duration of steroids (≤1 week) was 33.3% and increased to 57.1% with increasing duration of steroid treatment (>1 week). Conclusions: This study documented an increase in hospital based incidence of PCNSL in our institute, independent of HIV association. Steroid intake administration for more than a week prior to biopsy adversely affected the yield of STB in PCNSL.

Summary Background and purpose As both tuberculoma and metastasis can manifest as solitary or multiple ring-enhancing intra-axial lesions that are difficult to differentiate by conventional magnetic resonance imaging (MRI), we hypothesized that the use of diffusion and perfusion MRI would make differentiation of these pathologies possible. Materials and methods Diffusion and T2*-weighted dynamic contrast-enhanced perfusion MRI scans from 11 patients with histologically proven tuberculoma or metastasis were retrospectively reviewed by two radiologists who were blinded to the pathology. All patients had a ring-enhancing lesion on conventional MRI. Apparent diffusion coefficient (ADC) values and regional cerebral blood volume (rCBV) were calculated from the walls of the lesions. Results Lesions showed different perfusion characteristics depending on whether they were due to tuberculosis or metastasis. The mean rCBV ratio between the lesion periphery and normal white matter was inferior to one for tubercular lesions and greater than five for metastases. However, ADC values were similar. Conclusion Measuring rCBV obtained by T2*-weighted dynamic contrast-enhanced perfusion MRI can help in differentiating intracranial tubercular mass lesions and metastases.

Purpose The purpose of our study was to determine the statistical significance of thresholds of relative cerebral blood volume (rCBV), apparent diffusion coefficient (ADC) and ADC ratios in grading cerebral gliomas. Materials and methods In this retrospective study, 51 patients with histopathologically confirmed primary cerebral gliomas who had undergone conventional MR imaging, dynamic contrast-enhanced T2*-weighted perfusion MR imaging and diffusion MR imaging were included. A retrospective blinded analysis of the imaging findings including the perfusion and diffusion parameters was done. The rCBV measurements were obtained from regions of maximum perfusion. Minimum ADC values were obtained from the region of maximum hypointensity within the tumor and from the corresponding opposite white matter. Tumor grade determined with the two methods were then compared with the histopathologic grade. Mann–Whitney tests were performed to compare the DWI and PWI between tumor types. Receiver operating characteristic analyses were performed to determine optimum thresholds for tumor grading and also to calculate the sensitivity, specificity, PPV, and NPV for identifying high-grade gliomas. Results Statistical analysis demonstrated a threshold value of 2.91 for rCBV to provide sensitivity, specificity, PPV, and NPV of 94.7, 93.75, 90.0, and 96.8%, respectively, in determining high-grade gliomas. An ADC value of 98.50 mm2/s was defined as a threshold below which tumors were classified as high-grade gliomas and a sensitivity, specificity, PPV, and NPV of 90, 87.1, 81.81 and 93.10% respectively, were obtained. Significant differences were noted in the rCBV ratios, ADC and ADC ratios between low- and high-grade gliomas (P

A 1-year-old girl, whose parents were second cousins, presented with developmental delay and regression of milestones. She had macrocephaly, generalized hypotonia, brisk reflexes, and hepatosplenomegaly. Ophthalmoscopic examination revealed bilateral macular cherry-red spots. MRI of the brain (figure) demonstrated …