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BACKGROUND: Cerebral vasospasm can complicate aneurysmal subarachnoid hemorrhage (aSAH), contributing to cerebral ischemia. We explored the role of remote ischemic preconditioning (RIPC) in reducing cerebral vasospasm and ischemia and improving outcomes after aSAH. MATERIALS AND METHODS: Patients with ruptured cerebral aneurysm undergoing surgical clipping and meeting the trial criteria were randomized to true RIPC (n = 13) (inflating upper extremity blood pressure cuff thrice to 30 mmHg above systolic pressure for 5 min) or sham RIPC (n = 12) (inflating blood pressure cuff thrice to 30 mmHg for 5 min) after ethical approval. A blinded observer assessed outcome measures-cerebral vasospasm and biomarkers of cerebral ischemia. We also evaluated the feasibility and safety of RIPC in aSAH and Glasgow Outcome Scale-Extended (GOSE). RESULTS: Angiographic vasospasm was seen in 9/13 (69%) patients; 1/4 patients (25%) in true RIPC group, and 8/9 patients (89%) in sham RIPC group (P = 0.05). Vasospasm on transcranial Doppler study was diagnosed in 5/25 (20%) patients and 1/13 patients (7.7%) in true RIPC and 4/12 patients (33.3%) in sham RIPC group, (P = 0.16). There was no difference in S100B and neuron-specific enolase (NSE) levels over various time-points within groups (P = 0.32 and 0.49 for S100B, P = 0.66 and 0.17 for NSE in true and sham groups, respectively) and between groups (P = 0.56 for S100B and P = 0.31 for NSE). Higher GOSE scores were observed with true RIPC (P = 0.009) unlike sham RIPC (P = 0.847) over 6-month follow-up with significant between group difference (P = 0.003). No side effects were seen with RIPC. CONCLUSIONS: RIPC is feasible and safe in patients with aSAH and results in a lower incidence of vasospasm and better functional outcome.

The problem of immobility of legs leading to a potentially life threatening condition including deep venous thrombosis (DVT) is well known. The reduced mobility of leg affects a large number of patients in a wide range of clinical scenarios spanning from swelling of the legs to pulmonary embolism. In normal human beings, an elegant system of venous return, both active and passive is responsible for prevention of deep venous thrombosis. The paper proposes a prophylaxis and exercise device that mimics the natural principles of venous return to promote the blood flow. The device is based on electromechanical actuation, and simultaneous alternating compression mechanism, that is compact and, suitably form fitted in design and additionally requires no specialised training for the usage. The device was tested on a healthy volunteer on two different days and findings support the efficacy of the prophylaxis and exercise device in significantly improving the blood flow rate in the lower limb. The prototype device is considered as a major step towards designing a clinically validated lower limb device.

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.

Persistent embryological connections between the anterior and posterior circulations are rare entities. Persistent hypoglossal artery is the second most common persistent carotid-basilar anastomosis. As it is often associated with hypoplasia of vertebral arteries, it poses a challenge during endovascular interventions. We present a case of a 32-year-old woman who presented with occipital headache of four weeks’ duration. Magnetic Resonance Angiography showed hypoplastic vertebral arteries with a persistent hypoglossal artery arising from the cervical segment of the left internal carotid artery and supplying the entire posterior circulation, associated with a dissecting aneurysm of the right posterior cerebral artery. Endovascular parent vessel occlusion was performed for the dissecting posterior cerebral artery aneurysm by navigating the guide catheter, microwire, and microcatheter through the persistent hypoglossal artery because the vertebral arteries were hypoplastic. Post-intervention, the patient did not develop any neurological deficit and was discharged in a stable condition.

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 .

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is increasingly being recognised to be associated with protean neuropsychiatric manifestations. Anti-NMDAR encephalitis is considered to be the most common amongst the autoimmune-mediated encephalitic disorders. It is caused by the autoantibodies against GluN1 subunits of N-methyl-D-aspartate (NMDA) receptor and manifests with prominent psychiatric symptoms, especially during the initial phase of illness. Literature anti-NMDAR encephalitis presenting with postpartum psychosis is scant. In this report, we present a 28-year-old lady with postpartum psychosis as presenting manifestation of anti-NMDAR encephalitis and discuss the neuropsychiatric manifestations of this emerging entity.

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.

Background Large studies analyzing magnetic resonance imaging correlates in different genotypes of mitochondrial disorders are far and few. This study sought to analyze the pattern of magnetic resonance imaging findings in a cohort of genetically characterized patients with mitochondrial disorders. Methods The study cohort included 33 patients (age range 18 months–50 years, M:F — 0.9:1) with definite mitochondrial disorders seen over a period of 8 yrs. (2006–2013). Their MR imaging findings were analyzed retrospectively. Results The patients were classified into three groups according to the genotype, Mitochondrial point mutations and deletions (n = 21), SURF1 mutations (n = 7) and POLG1 (n = 5). The major findings included cerebellar atrophy (51.4%), cerebral atrophy (24.2%), signal changes in basal ganglia (45.7%), brainstem (34.2%) & white matter (18.1%) and stroke like lesions (25.7%). Spinal cord imaging showed signal changes in 4/6 patients. Analysis of the special sequences revealed, basal ganglia mineralization (7/22), lactate peak on magnetic resonance spectrometry (10/15), and diffusion restriction (6/22). Follow-up images in six patients showed that the findings are dynamic. Comparison of the magnetic resonance imaging findings in the three groups showed that cerebral atrophy and cerebellar atrophy, cortical signal changes and basal ganglia mineralization were seen mostly in patients with mitochondrial mutation. Brainstem signal changes with or without striatal lesions were characteristically noted in SURF1 group. There was no consistent imaging pattern in POLG1 group. Conclusion Magnetic resonance imaging findings in mitochondrial disorders are heterogeneous. Definite differences were noted in the frequency of anatomical involvement in the three groups. Familiarity with the imaging findings in different genotypes of mitochondrial disorders along with careful analysis of the family history, clinical presentation, biochemical findings, histochemical and structural analysis will help the physician for targeted metabolic and genetic testing.

Objective The aim of this study is to share our experience in per-operative embolization of aggressive vertebral haemangioma and to compare the surgical outcome with existing modalities of management. Background Vertebral haemangioma accounts for 12% of benign lesions of the vertebral column detected incidentally. Rarely they may enlarge, cause pain and neurological deficit because of spinal cord compression, vertebral body or arch expansion, or pathological fracture. Treatment options for symptomatic vertebral haemangioma include pre-operative transarterial embolization, surgical excision, radiotherapy, and percutaneous injection of alcohol or methyl methacrylate. We present our experience of per-operative glue embolization for aggressive (Enneking stage 3) vertebral haemangiomas. Materials and methods We describe five patients with symptomatic vertebral haemangioma at the dorsal level who underwent per-operative glue embolization. After initial laminectomy, a tumorogram was obtained under fluoroscopic guidance through direct contrast injection via spinal needle inserted through the pedicles of vertebra at the involved level. Varied concentration of glue was injected via the same spinal needle. All patients underwent surgical decompression of the intraspinal epidural component in the same sitting along with posterior spinal stabilization of the adjacent levels in two patients. Results In all five patients, complete embolization of the tumour was possible per-operatively through the transpedicular approach along with adjunctive surgical decompression, and the blood loss was significantly less. Clinical follow-up of these patients at 12–48 months showed reduction in size of the epidural component, relief of cord compression, and significant improvement in their neurological deficits with no recurrence. Conclusion We conclude that per-operative embolization is a safe and efficacious adjunctive procedure with surgical decompression with or without spinal stabilization for the treatment of symptomatic vertebral haemangiomas.

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.

CONTEXT: Medical Education in Private Medical Colleges is a great contributor to stress among the medical students & possibly even in developing syndromic depression among medical students which is an area of concern worldwide. The objective of this study is to assess the prevalence of depressive symptoms and its associate factors among medical students. MATERIALS AND METHODS: A cross sectional survey was conducted among 400 medical students from first to fourth year in Private Medical College of South India. Beck Depression Inventory-II was used to assess the level of depression with score of 10 or higher considered depressive. Association between depression and sex, year of study, medium of teaching in 10+2, social factors like alcohol & other substance abuse, family history of depression & family problems, hostel-stay etc. were analyzed by EPI info version 7. RESULTS: A total of 400 medical students participated in the study and the overall prevalence was found to be 64%. The prevalence of depression was higher (79%) among newly entered students (1st year) as compared to 2nd, 3rd and 4th year which was 60%, 57% and 53%, respectively. It was statistically significant (X 2 =38.54, p=0.001252 with Yate's correction). Students who were facing language problem in their MBBS course, because English was not the medium of teaching in their 10+2, reported symptoms suggestive of depression (X 2 =9.2091, p=0.0024). On the other hand students who undertook regular physical exercise were likely to suffer less depression (statistically significant, X2=34, p=0.000). Students taking alcohol (X2=8.315, p=0.00392) and with other substance abuse (X2=6.277, p=0.01233) reported more symptoms suggestive of depression. There was no statistically significant difference in the prevalence of depression among students with family history and staying in hostel. CONCLUSIONS: Prevalence of depression is quite high in students of Private Medical College as revealed by this study. It is recommended that a screening may be carried out based on BDI-II scale at the end of first year and group counseling facilities by the Department of Psychiatry within the medical college should be made available to affected medical students to lead a healthier life.

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.

INTRODUCTION: Cerebral vasospasm is a dreaded complication of aneurysmal subarachnoid hemorrhage (aSAH) predisposing to delayed cerebral ischemia. We intend to study the cerebroprotective effects of remote ischemic preconditioning (RIPC) in patients with aSAH. MATERIALS AND METHODS: This is a single-center, prospective, parallel group, randomized, pilot trial, approved by the Institutional Ethics Committee. Patients with aSAH admitted to our hospital for surgical clipping; fulfilling the trial inclusion criteria will be randomized to true RIPC (n = 12) (inflating upper extremity blood pressure cuff thrice for 5 min to 30 mmHg above systolic blood pressure) or sham RIPC (n = 12) (inflating blood pressure cuff thrice for 5 min to 30 mmHg) in 1:1 allocation ratio using a computerized random allocation sequence and block randomization. RESULTS: Our primary outcome measure is vasospasm on cerebral angiography and transcranial Doppler study, and concentration of serum S100B and neuron-specific enolase at 24 h after RIPC and on day 7 of ictus. Our secondary outcomes are safety of RIPC, cerebral oxygen saturation, and Glasgow coma score, and extended Glasgow outcome scale scores at discharge and at 1, 3, and 6 months following discharge. Outcome measures will be assessed by an observer blinded to the study intervention. CONCLUSION: If our preliminary results demonstrate a beneficial effect of RIPC, this would serve as a clinically applicable and safe preemptive method of protection against cerebral ischemia.

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.

Mitochondrial oxidative phosphorylation (OXPHOS) disorders account for a variety of neuromuscular disorders in children. In this study mitochondrial respiratory chain enzymes were assayed in muscle tissue in a large cohort of children with varied neuromuscular presentations from June 2011 to December 2013. The biochemical enzyme deficiencies were correlated with the phenotypes, magnetic resonance imaging, histopathology and genetic findings to reach a final diagnosis. There were 85 children (mean age: 6.9±4.7years, M:F:2:1) with respiratory chain enzyme deficiency which included: isolated complex I (n=50, 60%), multiple complexes (n=24, 27%), complex IV (n=8, 9%) and complex III deficiencies (n=3, 4%). The most common neurological findings were ataxia (59%), hypotonia (59%) and involuntary movements (49%). A known mitochondrial syndrome was diagnosed in 27 (29%) and non-syndromic presentations in 57 (71%). Genetic analysis included complete sequencing of mitochondrial genome, SURF1, POLG1&2. It revealed variations in mitochondrial DNA (n=8), SURF1 (n=5), and POLG1 (n=3). This study, the first of its kind from India, highlights the wide range of clinical and imaging phenotypes and genetic heterogeneity in children with mitochondrial oxidative phosphorylation disorders.

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.

Background There are relatively few studies, which focus on peripheral neuropathy in large cohorts of genetically characterized patients with mitochondrial disorders. This study sought to analyze the pattern of peripheral neuropathy in a cohort of patients with mitochondrial disorders. Methods The study subjects were derived from a cohort of 52 patients with a genetic diagnosis of mitochondrial disorders seen over a period of 8 years (2006–2013). All patients underwent nerve conduction studies and those patients with abnormalities suggestive of peripheral neuropathy were included in the study. Their phenotypic features, genotype, pattern of peripheral neuropathy and nerve conduction abnormalities were analyzed retrospectively. Results The study cohort included 18 patients (age range: 18 months–50 years, M:F- 1.2:1).The genotype included mitochondrial DNA point mutations (n = 11), SURF1 mutations (n = 4) and POLG1(n = 3). Axonal neuropathy was noted in 12 patients (sensori-motor:n = 4; sensory:n = 4; motor:n = 4) and demyelinating neuropathy in 6. Phenotype-genotype correlations revealed predominant axonal neuropathy in mtDNA point mutations and demyelinating neuropathy in SURF1. Patients with POLG related disorders had both sensory ataxic neuropathy and axonal neuropathy. Conclusion A careful analysis of the family history, clinical presentation, biochemical, histochemical and structural analysis may help to bring out the mitochondrial etiology in patients with peripheral neuropathy and may facilitate targeted gene testing. Presence of demyelinating neuropathy in Leigh's syndrome may suggest underlying SURF1 mutations. Sensory ataxic neuropathy with other mitochondrial signatures should raise the possibility of POLG related disorder.

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.

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.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.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 mm(2)/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 (P0.0001).Combining PWI and DWI with conventional MR imaging increases the accuracy of pre-operative imaging grading of glial neoplasms. The rCBV measurements had the most superior diagnostic performance in predicting glioma grade. Absolute ADC values or ADC ratios were also helpful in preoperative grading of gliomas. Threshold values can be used in a clinical setting to evaluate tumors preoperatively for histologic grade and provide a means for guiding treatment and predicting postoperative patient outcome.

The magnetic resonance imaging (MRI) in a female patient who presented with headache and hearing loss revealed aberrant course of the petrous segment of internal carotid artery (ICA). Computed tomography (CT) of the temporal bone done to confirm the findings of MRI revealed aberrant course of right ICA, a persistent stapedial artery (PSA) and absent foramen spinosum on the same side. In addition patient had a cystic cochleovestibular anomaly on the right side with both conditions may probably be contributing to her hearing loss.

Bilateral hypertrophic olivary degeneration on brain MRI has been reported in a few metabolic, genetic and neurodegenerative disorders, including mitochondrial disorders. In this report, we sought to analyse whether bilateral symmetrical inferior olivary nucleus hypertrophy is specifically associated with mitochondrial disorders in children.This retrospective study included 125 children (mean age, 7.6 ± 5 years; male:female, 2.6:1) diagnosed with various metabolic and genetic disorders during 2005-2012. The routine MRI sequences (T1 weighted, T2 weighted and fluid-attenuated inversion-recovery sequences) were analysed for the presence of bilateral symmetrical olivary hypertrophy and central tegmental tract or dentate nuclei signal changes. The other imaging findings and the final diagnoses were noted.The cohort included patients with Leigh and Leigh-like syndrome (n = 25), other mitochondrial diseases (n = 25), Wilson disease (n = 40), Type 1 glutaric aciduria (n = 14), maple syrup urine disease (n = 13), giant axonal neuropathy (n = 5) and L-2 hydroxy glutaric aciduria (n = 3). Bilateral inferior olivary nucleus hypertrophy was noted in 10 patients, all of whom belonged to the Leigh and Leigh-like syndrome group.Bilateral hypertrophic olivary degeneration on MRI is relatively often, but not routinely, seen in children with Leigh and Leigh-like syndrome. Early detection of this finding by radiologists and physicians may facilitate targeted metabolic testing in these children.This article highlights the occurrence of bilateral hypertrophic olivary nucleus degeneration on MRI in children with Leigh and Leigh-like syndrome, compared with other metabolic disorders.

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 …