Spectrum of Movement Disorders of Late-Onset Niemann-Pick Disease Type C.

Niemann-Pick disease type C (NPC), is a rare lysosomal storage disorder, which has a variable presentation based on the age of onset. We describe five adult/adolescent-onset NPC cases presenting with a range of movement disorders along with vertical supranuclear gaze palsy as part of the clinical presentation. A diagnostic delay of 4-17 years from the symptom onset was found in this case series. A high index of clinical suspicion in adult/adolescent patients presenting with vertical supranuclear gaze palsy along with various movement disorder phenomenology can help in the early diagnosis of NPC.

Diagnostic added value of interictal magnetic source imaging in presurgical evaluation of persons with epilepsy: A prospective blinded study.

BACKGROUND AND PURPOSE: In presurgical evaluation for epilepsy surgery, information is sourced from various imaging modalities to accurately localize the epileptogenic zone. Magnetoencephalography (MEG) is a newer noninvasive technique for localization. However, there is limited literature to evaluate if MEG provides additional advantage over the conventional imaging modalities in clinical decision making. The objective of this study was to assess the diagnostic added value of MEG in decision making before epilepsy surgery. METHOD: This was a prospective observational study. Patients underwent 3 h of recording in a MEG scanner, and the resulting localizations were compared with other complimentary investigations. Added value of MEG (considered separately from high-density electroencephalography) was defined as the frequency of cases in which (i) the information provided by magnetic source imaging (MSI) avoided implantation of intracranial electrodes and the patient was directly cleared for surgery, and (ii) MSI indicated additional substrates for implantation of intracranial electrodes. Postoperative seizure freedom was used as the diagnostic reference by which to measure the localizing accuracy of MSI. RESULTS: A total of 102 patients underwent epilepsy surgery. MEG provided nonredundant information, which contributed to deciding the course of surgery in 33% of the patients, and prevented intracranial recordings in 19%. A total of 76% of the patients underwent surgical resection in sublobes concordant with MSI localization, and the diagnostic odds ratio for good (Engel I) outcome in these patients was 2.3 (95% confidence interval 0.68, 7.86; p = 0.183) after long-term follow-up of 36 months. CONCLUSION: Magnetic source imaging yields additional useful information which can significantly alter as well as improve the surgical strategy for persons with epilepsy.

Movement disorders associated with neuronal antibodies.

Movement disorders are one of the common clinical features of neurological disease associated with neuronal antibodies which is a group of potentially reversible disorder. They can present with hypokinetic or hyperkinetic types of involuntary movements and may have other associated neurological symptoms. The spectrum of abnormal movements associated with neuronal antibodies is widening. Some specific phenomenology of movement disorders are likely to give clue about the type of antibody, for instance, presence of paroxysmal dystonia (facio-brachial dystonic seizures) are a pointer toward presence of LGI-1 antibodies, and orofacial lingual dyskinesia is associated with NMDAR associated encephalitis. The presence of specific type of movement disorder allows high suspicion of testing of certain specific type of antibodies. In this review, we have discussed the various antibodies and the spectrum of movement disorder associated with them, highlighting if any distinct movement disorder allows the clinician to suspect type of antibody in a certain clinical context. We have also reviewed the treatment of the movement disorder associated with the neuronal antibodies. Physicians should have high index of suspicion of these disorders, as early institution of treatment options can lead to better outcome.

Langerhans cell histiocytosis presenting as a rapidly evolving frontotemporal syndrome.

Langerhans cell histiocytosis (LCH) is a rare disorder in adults which usually manifests with involvement of multiple organ systems, including the central nervous system. We describe an unusual case of biopsy-proven LCH presenting with frontotemporal-dominant cognitive impairment with hypothalamic involvement, along with multisystem disease. We propose that the dementia was probably an immune-mediated process triggered by LCH which responded dramatically to high-dose steroids.

Validation of ICH and ICH-GS Scores in an Indian Cohort: Impact of Medical and Surgical Management.

OBJECTIVE: Prognostic scores help in predicting mortality and functional outcome post intracerebral hemorrhage (ICH). We aimed to validate the ICH and ICH-GS scores in a cohort of Indian patients with ICH and observe the impact of any surgical intervention on prognostication. METHODS: This was an ambispective observational study of primary ICH cases enrolled between January 2014 and April 2018. Observed mortality on ICH and ICH GS scores for the entire cohort and individually for the medically and surgically managed patients was compared to the published mortality in the original derivation cohorts. RESULTS: 617 patients, (464 retrospective and 153 prospective) of ICH were included. In hospital mortality and 30-day mortality was 28.7% and 28.5% respectively. There was a significant association of increasing mortality with increasing ICH and ICH-GS scores. Area under receiver operating characteristic curve for 30-day mortality was 75.9% and 74.1% for ICH and ICH-GS scores respectively. However, mortality observed at individual scores was significantly less than previously reported. Among the surgically intervened patients (n = 265), both the expected mortality at baseline and discriminative ability of ICH and ICH-GS scores for 30-day mortality was significantly reduced following surgical intervention (ROC in surgically intervened groups: 59.9 (52.6-67.2) and 63(56-70) for ICH and ICH-GS scores respectively). CONCLUSIONS: Although ICH and ICH-GS scores are valid in Indian population, mortality at individual scores is lower than previously reported. Mortality prediction using ICH and ICH GS scores is significantly modified by surgical interventions. Thus, newer prognostic tools which incorporate surgical intervention need to be developed and validated in future.

Neuroleptic malignant syndrome as a presenting feature of subacute sclerosing panencephalitis.

Subacute sclerosing panencephalitis (SSPE) is a slowly progressive degenerative disorder caused by measles virus. It is characterised by typical clinical and electrophysiological features in the form of slow myoclonic jerks, with progressive cognitive impairment, visual symptoms, and periodic complexes on EEG, with raised titres of anti-measles antibodies in CSF and serum. Atypical presentations of SSPE have been reported including brainstem involvement, ADEM-like presentation, acute encephalitis, and cerebellar ataxia. Presentation with predominant extrapyramidal features is uncommon. We describe a case of SSPE presenting with extensive rigidity with highly elevated CPK values, mimicking neuroleptic malignant syndrome (NMS) which was most probably due to central dopaminergic blockade induced by the disease process. To our knowledge, this is the first case of SSPE presenting with a NMS-like syndrome.

Randomized controlled study comparing the efficacy of rapid and slow withdrawal of antiepileptic drugs during long-term video-EEG monitoring.

OBJECTIVE: Antiepileptic drugs (AEDs) are routinely withdrawn during long-term video-electroencephalography (EEG) monitoring (LTM), to record sufficient number of seizures. The efficacy of rapid and slow AED taper has never been compared in a randomized control trial (RCT), which was the objective of this study. METHODS: In this open-label RCT, patients aged 2-80 years with drug-resistant epilepsy (DRE) were randomly assigned (1:1) to rapid and slow AED taper groups. Outcome assessor was blinded to the allocation arms. Daily AED dose reduction was 30% to 50% and 15% to <30% in the rapid and slow taper groups, respectively. The primary outcome was difference in mean duration of LTM between the rapid and slow AED taper groups. Secondary outcomes included diagnostic yield, secondary generalized tonic-clonic seizure (GTCS), 4- and 24- hour seizure clusters, status epilepticus, and need for midazolam rescue treatment. The study was registered with Clinical Trial Registry-India (CTRI/2016/08/007207). RESULTS: One hundred forty patients were randomly assigned to rapid (n = 70) or slow taper groups (n = 70), between June 13, 2016 and February 20, 2017. The difference in mean LTM duration between the rapid and slow taper groups was -1.8 days (95% confidence interval [CI] -2.9 to -0.8, P = .0006). Of the secondary outcome measures, time to first seizure (2.9 ± 1.7 and 4.6 ± 3.0 days in the rapid and slow taper groups respectively, P = .0002) and occurrence of 4-hour seizure clusters (11.9% and 2.9% in the rapid and slow taper groups, respectively, P = .04) were statistically significant. None of the other safety variables were different between the 2 groups. LTM diagnostic yield was 95.7% and 97.1%, in rapid and slow taper groups respectively (P = .46). SIGNIFICANCE: Rapid AED tapering has the advantage of significantly reducing LTM duration over slow tapering, without any serious adverse events.

Effect of providing sudden unexpected death in epilepsy (SUDEP) information to persons with epilepsy (PWE) and their caregivers-Experience from a tertiary care hospital.

OBJECTIVE: The primary objective of present study was to observe the effect of providing SUDEP (Sudden Unexpected Death in Epilepsy) information on drug adherence in persons with epilepsy (PWE). We also looked at impact of disclosing SUDEP information on patient's quality of life and mood. MATERIAL AND METHODS: This prospective study had a pretest/post-test design. A total of 231 consecutive PWE (>15 years) were enrolled. Of these 121 PWE received information about SUDEP in addition to standard epilepsy care. One hundred and ten PWE (control group) received routine standard epilepsy care but did not receive SUDEP information. Follow up assessment was done at 6 months. The primary outcome was a change in drug adherence (measured by Modified Morisky Medication Adherence Scale, MMAS) in PWE following disclosure of SUDEP information. RESULTS: After 6 months, 116 PWE in the SUDEP information group and 106 in control group were available for follow up. A non-significant higher adherence was observed in the SUDEP information group as compared to the control group (Mean MMAS change 0.51 ± 1.66 vs 0.25 ± 1.26, P value = 0.194). No significant change was perceived in patient's anxiety and depression levels or quality of life in either group. CONCLUSION: The present study suggests that providing information on SUDEP to PWE and their caregivers may increase drug adherence without adverse effect on quality of life or mood. Well-designed studies with high methodological quality are required to determine the precise effect size associated with disclosure of SUDEP information on drug adherence in PWE.

Metabolic topography of autoimmune non-paraneoplastic encephalitis.

PURPOSE: F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) is emerging to be a useful tool in supporting the diagnosis of AIE. In this study, we describe the metabolic patterns on F-18 FDG PET imaging in AIE. METHODS: Twenty-four antibody-positive patients (anti-NMDA-15, anti-VGKC/LGI1-6, and anti-GAD-3), 14 females and 10 males, with an age range of 2-83 years were included in this study. Each PET study was evaluated visually for the presence of hypometabolism or hypermetabolism and semiquantitatively using Cortex ID (GE) and Scenium (Siemens) by measuring regional Z-scores. These patterns were correlated with corresponding antibody positivity once available. RESULTS: Visually, a pattern of hypometabolism, hypermetabolism, or both in various spatial distributions was appreciated in all 24 patients. On quantitative analysis using scenium parietal and occipital lobes showed significant hypometabolism with median Z-score of -3.8 (R) and -3.7 (L) and -2.2 (R) and -2.5 (L) respectively. Two-thirds (16/24) showed significant hypermetabolism involving the basal ganglia with median Z-score of 2.4 (R) and 3.0 (L). Similarly on Cortex ID, the median Z-score for hypometabolism in parietal and occipital lobes was -2.2 (R) and -2.4 (L) and -2.6 (R) and -2.4 (L) respectively, while subcortical regions were not evaluated. MRI showed signal alterations in only 11 of these patients. CONCLUSION: There is heterogeneity in metabolic topography of AIE which is characterized by hypometabolism most commonly involving the parietal and occipital cortices and hypermetabolism most commonly involving the basal ganglia. Scenium analysis using regional Z-scores can complement visual evaluation for demonstration of these metabolic patterns on FDG PET.

Impact of health education on drug adherence and self-care in people with epilepsy with low education.

PURPOSE: This study was conducted to observe the effect of a structured educational program on drug adherence and self-care management in people with epilepsy in a developing country. METHODS: A total of 180 consecutive people with epilepsy were enrolled from the epilepsy clinic of a tertiary care hospital in North India. Out of these, 90 were randomized to the epilepsy health education group and received the educational program and 90 were in the control group and received the standard of care but did not receive any structured educational program. The modified Morisky Medication Adherence Scale (MMAS) and Epilepsy Self-Efficacy Scale (ESES) were administered to assess drug adherence and self-care, respectively, on the day of enrollment. The patients enrolled in the epilepsy health education group received 4 sessions of the structured educational program. The MMAS and ESES questionnaires were again administered to both groups after 6months. STATISTICAL METHODS: Continuous and categorical variables were compared between control and epilepsy health education groups using a chi-square test, with p value less than 0.05 considered significant. A comparison between pretest and posttest MMAS scores and ESES scores was done using a paired t-test. RESULTS: In the epilepsy health education group, the pretest mean MMAS score was 6.58 whereas the posttest mean MMAS score was 7.53; the difference was significant (p=0.001). The mean MMAS scores for the control group's pretest and posttest were 6.46 and 6.58, respectively, which were not significantly different (p=0.224). On comparing the ESES scores at the beginning of the study and after 6months, there was no significant change in both groups. CONCLUSIONS: The present study proves the efficacy of a structured educational program in improving drug adherence in a cohort of people with epilepsy with low educational background.

History of neurology at All India Institute of Medical Sciences.

All India Institute of Medical Sciences (AIIMS), New Delhi is considered as the apex healthcare institute of the country. The Department of Neurology was established in the 1960's and continues to be a leader in the country, in providing quality health care, in teaching, and also in conducting cutting edge research. The article traces the history of the Department of Neurology at AIIMS from its inception to the present day.

Cerebral venous thrombosis: An Indian perspective.

Cerebral venous thrombosis (CVT) is an uncommon cause of stroke with extremely varied clinical presentations, predisposing factors, imaging findings, and outcomes, and thus can be extremely challenging to diagnose. Accurate and prompt diagnosis of CVT is crucial because timely and appropriate therapy can reverse the disease process and significantly reduce the risk of acute complications and long-term squel. In this article, we have reviewed the epidemiology, causative factors, clinical features, diagnosis and treatment of CVT from an Indian perspective. Over the last decade, a change in trends in the causative factors has been noted from India.

The role of susceptibility-weighted imaging & contrast-enhanced MRI in the diagnosis of primary CNS vasculitis: a large case series.

Primary CNS Vasculitis (PCNSV) is a rare, diverse, and polymorphic CNS blood vessel inflammatory condition. Due to its rarity, clinical variability, heterogeneous imaging results, and lack of definitive laboratory markers, PCNSV diagnosis is challenging. This retrospective cohort analysis identified patients with histological diagnosis of PCNSV. Demographic data, clinical presentation, neuroimaging studies, and histopathologic findings were recorded. We enrolled 56 patients with a positive biopsy of CNS vasculitis. Most patients had cerebral hemisphere or brainstem symptoms. Most brain MRI lesions were bilateral, diffuse discrete to confluent white matter lesions. Frontal lobe lesions predominated, followed by inferior cerebellar lesions. Susceptibility-weighted imaging (SWI) hemorrhages in 96.4% (54/56) of patients, either solitary microhemorrhages or a combination of micro and macrohemorrhages. Contrast-enhanced T1-WIs revealed parenchymal enhancement in 96.3% (52/54 patients). The most prevalent pattern of enhancement observed was dot-linear (87%), followed by nodular (61.1%), perivascular (25.9%), and patchy (16.7%). Venulitis was found in 19 of 20 individuals in cerebral DSA. Hemorrhages in SWI and dot-linear enhancement pattern should be incorporated as MINOR diagnostic criteria to diagnose PCNSV accurately within an appropriate clinical context. Microhemorrhages in SWI and venulitis in DSA, should be regarded as a potential marker for PCNSV.

Motor band sign in a Huntington disease phenocopy.

We report a 68-year-old lady who presented with Huntington phenocopy with generalized chorea and was genetically proven to have Spinocerebellar ataxia (SCA)17. MRI Brain demonstrated motor band sign, which is most commonly reported in motor neuron disease. This is the first case of motor band sign with SCA 17 and highlights the widening spectrum of radiological signs in SCA 17.

Validation of the Hindi version of National Institute of Health Stroke Scale.

AIMS: To determine the reliability and validity of the National Institute of Health Stroke Scale (NIHSS) with the Hindi and Indian adaptation of items 9 and 10. MATERIALS AND METHODS: NIHSS items 9 and 10 were modified and culturally adapted at All India Institute of Medical Sciences (AIIMS) and the resulting version was termed as Hindi version (HV-NIHSS). HV-NIHSS was applied by two independent investigators on 107 patients with stroke. Inter-observer agreement and intra-class correlation coefficients were calculated. The predictive validity of the HV-NIHSS was calculated using functional outcome after three months in the form of modified Rankin Scale (mRS) and Barthel Index (BI). RESULTS: The study included 107 patients of stroke recruited from a tertiary referral hospital at Delhi between November 1, 2009, and October 1, 2010; the mean age of these patients was 56.26±13.84 years and 65.4% of them had suffered ischemic stroke. Inter-rater reliability was high between the two examiners, with Pearson's r ranging from 0.72 to 0.99 for the 15 items on the Scale. Intra-class correlation coefficient for the total score was 0.995 (95% CI-0.993-0.997). Concurrent construct validity was established between HV-NIHSS and baseline Glasgow Coma Scale, with a high correlation (Spearman coefficient = -0.863, P<.001). Predictive validity was also established with BI at three months (Spearman's rho: -0.829, P<.001) and with mRS at three months (Spearman's rho: 0.851, P<0.001). CONCLUSIONS: This study shows that a Hindi language version of the NIHSS developed at AIIMS appears reliable and valid when applied to a Hindi-speaking population.

Evaluation of the Impact of Integrated Care and Self-Management After Deep Brain Stimulation in Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder with a myriad of motor and non-motor symptoms. Although deep brain stimulation (DBS) has a dramatic impact in the lives of people with PD, care delivery remains complex. There is a lack of evidence on the implementation and role of integrated care and self-management support in people with PD with chronic DBS. OBJECTIVE: To evaluate care needs, implementation and impact of a pragmatic network for PD care, the Integrated Parkinson Care Network (IPCN). METHODS: This is a subgroup analyses of a 6-month, pre-post design, single-centre, phase 2 study to assess a patient-centred care model based on integrated care, self-management support (IPCN) in PD, focusing on those participants with chronic DBS. RESULTS: We included 22 people with PD and chronic DBS (median time since DBS - 30 months). The mean age was 63.9 (7.6) years and mean disease duration was 15.2 (6.9) years. The top three care priorities were speech (54.5%), mobility (40.9%) and mood (31.8%). After the IPCN program, there was a positive change in the perception of support for chronic care (Patient Assessment of Chronic Illness Case: 0.85; 95% CI: 1.2 to -0.4) and self-management (5As: 0.77; 95% CI: 0.39 -1.15), along with quality of life (PDQ8 : 7.1, 95% CI:1.8 -12.4). CONCLUSION: The IPCN is a care delivery model that addresses specific care needs of people with PD and chronic DBS. The current study showed its feasibility and warrants further evaluation.

Primary CNS vasculitis (PCNSV): a cohort study.

Primary CNS Vasculitis (PCNSV) is a rare inflammatory disorder affecting the blood vessels of the central nervous system. Patients present with a combination of headaches, seizures, and focal neurological deficits. There is usually a diagnostic delay. Treatment is based on observational studies and expert opinion. Our objective was to identify clinical, laboratory, neuroimaging, pathologic or management-related associations with 2 year outcome in patients with primary CNS vasculitis. We conducted a cohort study at a single tertiary care referral centre of prospectively (2018-2019) and retrospectively (2010-2018) identified individuals with primary CNS vasculitis (diagnosis was proven by either brain biopsy or cerebral digital subtraction angiography). Clinical, imaging and histopathologic findings, treatment, and functional outcomes were recorded. Univariate and stepwise multiple logistic regression were applied. P-value<0.05 was considered statistically significant. The main outcome measures were documentation of clinical improvement or worsening (defined by mRS scores) and identification of independent predictors of good functional outcome (mRS 0-2) at 2 years. We enrolled eighty-two biopsy and/or angiographically proven PCNSV cases. The median age at presentation was 34 years with a male predilection and a median diagnostic delay of 23 months. Most patients presented with seizures (70.7%). All patients had haemorrhages on MRI. Histologically lymphocytic subtype was the commonest. Corticosteroids with cyclophosphamide was the commonest medication used. The median mRS at follow-up of 2 years was 2 (0-3), and 65.2% of patients achieved a good functional outcome. Myelitis and longer duration of illness before diagnosis were associated with poorer outcomes. The presence of hemorrhages on SWI sequence of MRI might be a sensitive imaging marker. Treatment with steroids and another immunosuppressant probably reduced relapse rates in our cohort. We have described the third largest PCNSV cohort and multi-centre randomised controlled trials are required to study the relative efficacy of various immunosuppressants.Study registration: CTRI/2018/03/012721.