Analysis of Semiology, Lesion Topography and Treatment Outcomes: A Prospective Study on Post Thalamic Stroke Holmes Tremor.

OBJECTIVE: Holmes tremor (HT) comprises rest, postural and intention tremor subtypes, usually involving both proximal and distal musculature. Perturbations of nigro-striatal pathways might be fundamental in the pathogenesis of HT along with cerebello-thalamic connections. METHODS: Nine patients with an HT phenotype secondary to thalamic stroke were included. Epidemiological and clinical records were obtained. Structural and functional brain imaging were performed with magnetic resonance imaging (MRI) or computed tomography (CT) and positron emission tomography (PET), respectively. Levodopa was administered in sequentially increasing dosage, with various other drugs in case of inadequate response. Longitudinal follow-up was performed for at least three months. The essential tremor rating assessment scale (TETRAS) was used for assessment. RESULTS: The mean latency from stroke to tremor onset was 50.4 ± 30.60 days (range 21-90 days). Dystonia was the most frequently associated hyperkinetic movement (88.8%). Tremor was bilateral in 22.2% of participants. Clinical response was judged based on a reduction in the TETRAS score by a prefixed value (≥ 30%), pertaining to which 55.5% (n = 5) of subjects were classified as responders and the rest as non-responders. The responders showed improvement with significantly lower doses of levodopa than the remaining nonresponders (240 ± 54.7 mg vs. 400 ± 40.8 mg; p = 0.012). CONCLUSION: Although levodopa is useful in HT, augmenting the dosage of levodopa beyond a certain point might not benefit patients clinically. Topography of vascular lesions within the thalamus might additionally influence the phenomenology of HT.

Parakinesia Brachialis Oscitans - a Rare Post-Stroke Phenomenon.

Background: Abnormal involuntary movement of paralyzed upper limb during yawning is a rare phenomenon termed as parakinesia brachialis oscitans. Case Report: We describe a 59-year-old gentleman with abnormal involuntary movement of paralyzed right upper limb during yawning 2 weeks following ischemic stroke of left middle cerebral artery territory. Discussion: This is a rare post-stroke phenomenon and its pathophysiological mechanism is poorly understood but this entity highlights possible preserved extrapyramidal pathway which might help in rehabilitating stroke survivors.

A video-based discussion of movement disorders in paediatric anti NMDAR encephalitis: A case series from Eastern India.

PURPOSE: The spectrum of movement disorders associated with anti N-Methyl-d-Aspartate-Receptor (NMDAR) encephalitis is myriad, particularly in children, possibilities of which were investigated from two tertiary care centres. METHODS: A retrospective study was conducted in two tertiary referral centres in Eastern India, analysing data of 8 paediatric patients diagnosed as anti NMDAR encephalitis, presenting with one or more movement disorders (MDs). RESULTS: All the patients were of Bengali ethnicity with a median age of 9 years (3-16 years) and with female predilection (62.5%). CSF pleocytosis was a common feature in all. Seizures were described in 62.5%% of patients with a solitary patient exhibiting abnormalities on brain imaging. 3 out of 8 (37.5%) of patients presented with a single MD while the remaining had more than one type. Oro-linguo-facial dyskinesias and dystonia (37.5% each) were the most common movement type followed by chorea (12.5%). Complex stereotypies, myoclonus and facial tics were noted in one patient each. All patients received pulse methyl prednisolone. Escalation to second line therapy in form of rituximab was done for 5 patients (62.5%). Following immunotherapy, hyperkinetic movements resolved in 50% of patients, with persistence of movements in one (12.5%). A mortality of 37.5% was noted. Median duration of follow up was 26 months, during which none of the patients had evidence of systemic neoplasm. CONCLUSION: MDs are a core feature of anti NMDAR encephalitis, particularly in the paediatric age group, understanding and characterization of which, is the key to early diagnosis and effective therapy.

Correlation of ATP7B gene mutations with clinical phenotype and radiological features in Indian Wilson disease patients.

INTRODUCTION: Wilson disease (WD) is characterized by a wide variety of clinical manifestations. Our study aimed to correlate genotype with clinical and radiological features in Indian WD patients. METHODS: We conducted a descriptive observational study in a tertiary care neurology referral center of eastern India over a period of 2 years. Demographic data collection, clinical examination and relevant investigations were done for all WD patients meeting the inclusion criteria. Based on previous reports of mutation hotspots for WD in Eastern India, we performed PCR-Sanger sequencing of selected exons of ATP7B gene. To understand the role of each of these covariates on the occurrence of common mutation, we applied a logistic regression as well as random forest in a supervised learning framework. RESULTS: Fifty-two WD patients were included in the study. c.813C > A (p.C271X) was the commonest identified mutation. The statistical methods applied to our data-set reveal the most important features for predicting common mutation or its absence. We also found that the state-of-the-art classification algorithms are good at predicting the absence of common mutation (with true positive rates being 0.7647 and 0.8823 for logistic classifier and random forest, respectively), but predicting the occurrence remains a harder modeling challenge. CONCLUSIONS: WD patients in eastern India have significant genotypic and phenotypic diversity. Statistical methods for binary classification show some early promise of detecting common mutations and suggest important covariates, but further studies with larger samples and screening of remaining exons are warranted for understanding the full genetic landscape of Wilson disease.

Recurrent ataxia and dysarthria in myelin oligodendrocyte glycoprotein antibody-associated disorder.

The spectrum of central nervous system demyelinating disorders is vast and heterogeneous and, often, with overlapping clinical presentations. Misdiagnosis might occur in some cases with serious therapeutic repercussions. However, introduction of several new biomarkers such as aquaporin-4 IgG and myelin oligodendrocyte glycoprotein IgG has made distinction between diseases such as multiple sclerosis and myelin oligodendrocyte glycoprotein antibody-associated disorder easier. Here, we report a case of a 15-year-old male patient with subacute multifocal neurological presentation without encephalopathy, eventually diagnosed as myelin oligodendrocyte glycoprotein antibody-associated disorder.

Not the Stereotypical Wilson Disease: A Case Report.

Background: Wilson disease (WD), a potentially treatable genetic disorder with perturbations in copper metabolism, presents with hepatic and neuropsychiatric manifestations. Both hyper and hypokinetic movements predominate the latter spectrum. Motor stereotypies, however, are exceedingly rare. Case Report: We present a case of a 12-year-old girl, with progressive behavioural alterations and cognitive impairment, with motor stereotypies involving the upper limbs, as the dominant movement semiology. She was diagnosed as WD with evidence of striatal involvement on brain imaging. Her motor symptoms partially responded to chelation therapy. Discussion: There are about five documented cases of motor stereotypies in WD worldwide, with only one being previously reported from India.

Spectrum of Anti-NMDA Receptor Antibody Encephalitis: Clinical Profile, Management and Outcomes.

BACKGROUND: Anti-N-methyl D-aspartate receptor (anti NMDAR) antibody encephalitis is an immune-mediated entity characterised by a constellation of neuro-psychiatric symptoms. OBJECTIVE: To describe clinical profile and treatment outcomes of patients with anti NMDAR antibody encephalitis. SETTINGS AND DESIGN: Subjects were selected by screening for all patients satisfying Graus et al.'s criteria for probable anti NMDAR antibody encephalitis, admitted in neurology department of a tertiary care centre in Eastern India. MATERIALS AND METHODS: A prospective, longitudinal study was conducted by identifying 25 patients with anti NMDAR antibodies in CSF and or serum, between September 2018 to February 2020. STATISTICAL ANALYSIS: Chi square test was used to compare variables. RESULTS: Out of 98 patients screened, 25 subjects (14 females: 11 male) were positive for anti NMDAR autoantibodies, with a mean age of 17 years. 13 subjects belonged to paediatric age group. Most common presenting feature was memory/learning deficit (88%) followed by behavioural abnormalities (84%) and seizures (68%). 11 patients (44%) patients needed escalation to second line therapy, rituximab. Seven (28%) and twelve (48%) patients underwent complete (mRS 0-1) and partial recovery (mRS 2-3) respectively, while 4 (16%) became disabled (mRS 4-5). Mortality was 8%. Paediatric population had a better outcome in terms of disability (p = 0.043). CONCLUSION: Anti NMDAR-Ab encephalitis is the most common cause of antibody positive autoimmune encephalitis worldwide. There are important clinical markers and investigational profiles which carry prognostic significance.

Anti-MOG antibody associated long segment myelitis presenting as anterior cord syndrome.

A patient having clinical features reminiscent of anterior cord syndrome (ACS) was found to have long segment myelitis on MRI. Investigations revealed serum anti-myelin oligodendrocyte glycoprotein (MOG) antibody positivity. He was treated with pulse methylprednisolone followed by immunosuppressant therapy with mycophenolate mofetil, which led to clinical recovery. Anterior cord syndrome has so far not been reported in the context of anti-MOG antibody associated disease.

Adult-onset Kawasaki disease: A great masquerader.

Kawasaki disease is a necrotising small-to-medium vessel vasculitis affecting children between age groups of 6 months and 5 years. Following the first description in Japanese infants, it has been recognised as the single most common cause of non-infectious vasculitis in children worldwide. Presentation in adult age groups, although described, is rare. Herein, we report a case about a 19-year-old female Indian patient diagnosed with Kawasaki disease and managed with antiplatelets and intravenous immunoglobulin, without further sequalae. We aim to highlight the importance of recognising this entity in adult age groups in day-to-day clinical practice.

Moyamoya disease: a spectrum of clinical and radiological findings in a series of eight paediatric patients.

Moyamoya disease (MMD) is a progressive steno-occlusive vasculopathy at the circle of Willis, characteristically involving the supra-clinoid segment of internal carotid arteries and their proximal branches with prominent collateral artery formation. Here we present, a series of imaging findings and varied clinical presentation of eight cases (n = 8) of MMD in the pediatric population (aged 0-18 years) after a retrospective review and detailed clinical evaluation. Detailed clinical history and examination were performed of eight pediatric patients of MMD with varied presentations. Magnetic resonance imaging (MRI) of the brain along with time of flight (TOF) sequence magnetic resonance angiography (MRA) was performed for all patients with a 3 T ((T) SEIMENS MRI scanner. Three out of eight cases (37.5%) presented with imaging findings of acute parenchymal infarction involving one or more major vascular territories showing diffusion restriction on DWI (diffusion-weighted image) sequence. Two of the patients (25%) showed chronic infarction with areas of gliosis and encephalomalacia. One child presented with watershed areas of infarction involving bilateral parieto-occipital region. In one of the patients (12.5%) being evaluated for dystonia, the only parenchymal finding detected was that of asymmetric ventriculomegaly. A solitary patient being evaluated for intermittent focal seizure followed by Todd's hemiparesis had normal parenchymal brain imaging. Leptomeningeal pattern of enhancement was noted in one patient (12.5%). Although predominantly an intracranial vasculopathy, MMD may have myriad presentations apart from stroke, some of which are highlighted in this series.

Acute viral hepatitis E complicated with acute pancreatitis in an immunocompetent adult.

Acute viral hepatitis has been associated with several extrahepatic complications. Fulminant liver failure secondary to acute viral hepatitis may be complicated by acute pancreatitis. However, in the setting of benign viral hepatitis, in the absence of liver failure, association of pancreatitis is uncommon, that too in an otherwise immunocompetent individual. The exact mechanism of hepatitis-related pancreatitis remains elusive. Proposed mechanisms include immune-mediated injury against infected pancreatic acinar cells, oedema of the ampulla of Vater and release of lysosomal enzymes from the liver. A high index of clinical suspicion is needed in any case of viral hepatitis with severe abdominal pain to recognise acute pancreatitis as a possible complication, which may increase both morbidity and mortality if unrecognised. Herein, we report a case of a young man presenting with acute viral hepatitis due to hepatitis E infection, complicated by acute pancreatitis.

Clostridioides difficile-induced diarrhoea following dasatinib therapy.

Dasatinib, an oral tyrosine kinase inhibitor, is approved for therapy of chronic myeloid leukaemia (CML). Common adverse effects of this therapy include myelosuppression, fluid retention and diarrhoea. However, Clostridioides difficile infections (CDIs) in the context of dasatinib therapy, without a history of antecedent antibiotic use, has not been reported previously. We present here a case of a 36-year-old man diagnosed with accelerated phase of CML, who was started on treatment with dasatinib. Two months into therapy, he experienced profuse diarrhoea and abdominal pain. Colonoscopy revealed multiple confluent colonic mucosal ulcerations. Immunoassay study of stool revealed positive C. difficile toxin. The patient was started on oral metronidazole, with discontinuation of all other drugs, including dasatinib. He made a complete uneventful recovery following 2 weeks of antibiotic therapy. Chemotherapeutic agents, such as dasatinib, should be considered as possible etiological agents in the pathogenesis of CDI, even in absence of antibiotic use.