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The COVID-19 pandemic evolved rapidly, overwhelming health care systems around the world. The cost to life and socioeconomic burden prompted a search for new treatments and vaccines. Several collaborations developed and could deliver state-of-the-art vaccines with acceptable efficacy and safety in record time. Recently, vaccination with Oxford-AstraZeneca and Johnson and Johnson vaccines was halted due to the reported adverse effects of vaccine-induced immune thrombotic thrombocytopenia (VITT) and cerebral venous sinus thrombosis (CVST). Although a detailed risk-benefit analysis led to their reinstitution, physicians across the world are still trying to understand the pathophysiology and mechanisms of these neurological adverse effects in order to better identify, diagnose, and treat them. One of the mechanisms that have been implicated is related to the adenovirus-based vector of these vaccines. COVISHIELD, which is the most widely administered vaccine in India, also shares the same vector. As India enters the next phase of vaccine distribution for younger adults, there are chances that such adverse effects may emerge. In this review, we analyze the temporary suspension of the administration of the vaccines due to VITT/CVST, summarize the existing guidelines about diagnosis and treatment of these neurological disorders as well as the need for increasing pharmacovigilance and awareness among physicians. Screening for potential risk factors, avoiding aggravating factors like dehydration, and providing choices in vaccinating the high-risk populations could help in avoiding these rare but potentially fatal adverse outcome.

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During the second wave of COVID-19 pandemic, there is a sudden increase in number of cases mucormycosis infection in India. This communication by the Tropical Neurology subsection expert group of the Indian Academy of Neurology (IAN) describes the clinical and diagnostic features, treatment of the disease and gives recommendations about the ways forward.

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Objective: To study impact of COVID-19 pandemic on frequency, clinical/electrophysiological profile and treatment outcomes in pediatric Guillain-Barré syndrome (GBS). Background: GBS is the most frequent cause of pediatric acute flaccid paralysis. The effect of the COVID-19 pandemic on pediatric GBS is unclear in the literature. Methods: We conducted an ambispective, multicentric, cohort study involving 12 of 27 centres in GBS Consortium, during two periods: pre-COVID-19 (March-August 2019) and during COVID-19 (March-August 2020). Children ≤12 years who satisfied National Institute of Neurological Diseases and Stroke criteria for GBS/variants were enrolled. Details pertaining to clinical/laboratory parameters, treatment and outcomes (modified Rankin Scale (mRS) at discharge, GBS Disability score at discharge and 3 months) were analysed. Results: We enrolled 33 children in 2019 and 10 in 2020. Children in 2020 were older (median 10.4 [interquartile range 6.75–11.25] years versus 5 (2.5–8.4) years; P = 0.022) and had more sensory symptoms (50% versus 18.2%; P = 0.043). The 2020 group had relatively favourable mRS at discharge (median 1 (1–3.5) versus 3 (2–4); P = 0.042) and GBS disability score at 3 months (median 0 (0–0.75) versus 2 (0–3); P = 0.009) compared to 2019. Multivariate analysis revealed bowel involvement (P = 0.000) and ventilatory support (P = 0.001) as independent predictors of disability. No child in 2020 had preceding/concurrent SARS-CoV2 infection. Conclusions: The COVID-19 pandemic led to a marked decline in pediatric GBS presenting to hospitals. Antecedent illnesses, clinical and electrophysiological profile of GBS remained largely unchanged from the pre-pandemic era.

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Oromandibular dystonia (OMD) is a clinical problem which is commonly encountered in the practice of movement disorders. OMD results from a variety of genetic and acquired etiologies and can occur as an isolated manifestation, or as part of an isolated generalized or a combined dystonia syndrome. There are only very few systematic reviews on this condition which often causes significant disability. We review here the etiology, clinical features, diagnostic approach and management of OMD.

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Background: The recovery of the upper-limb (UL) motor function after ischemic stroke (IS) remains a major scientific, clinical, and patient concern and it is hard to predict alone from the clinical symptoms. Objective: To determine the accuracy of the prediction of the recovery of UL motor function in patients with acute ischemic middle cerebral artery (MCA) stroke using individual clinical, transcranial magnetic stimulation (TMS) or diffusion tensor imaging (DTI) parameters or their combination. Methods and Material: The first-ever acute ischemic MCA stroke patients within 7 days of the stroke onset who had an obvious UL motor deficit underwent TMS for the presence of motor-evoked potential (MEP) and DTI to evaluate the integrity of corticospinal tracts. Multivariate logistic regression analysis was done to test for the accuracy of the prediction of the recovery of UL motor function. Results: Twenty-nine acute ischemic MCA stroke patients (21 males and 8 females) with a mean age of 51.45 ± 14.26 years were recruited. Model-I included clinical scales (Fugl-Meyer Assessment [FMA] + Motricity Index [MI]) + TMS (MEP) + DTI (fractional anisotropy [FA]) were found to be the most accurate predictive model, with the overall predictive ability (93.3%; 95% confidence interval [CI]: 0.87–0.99) and sensitivity: 94.9% (95% CI: 0.87–1.0) and specificity: 95.8% (95% CI: 0.89–1.0); respectively. Conclusion: The accuracy of UL motor recovery can be predicted through the clinical battery and their elements as well as TMS (MEP) and DTI (FA) parameters. Further, well-designed prospective studies are needed to confirm our findings.

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Ischemic stroke is a major cause of acute neurological symptoms in children with significant long-term neurological sequelae. Unlike in the adult population, the clinical presentation of strokes in children may not be stereotyped. Hence, many other differential diagnostic possibilities might have to be considered in the emergency setting. Due to this heterogeneous presentation and the resultant clinical dilemma in the early detection, acute thrombolysis even now remains as a very rarely tried therapeutic option in children. Many case reports over these years have shown consistently good results of acute intravenous thrombolysis in children with tissue plasminogen activator (tPA) administered within the time frame. There are also some recent reports of endovascular interventions. However, unlike in the adult population, class 1 clinical studies and good Randomized controlled trials (RCT) are yet to emerge in children. The absence of age-appropriate safety and outcome data for the commonly used thrombolytic agents in children is another major roadblock for developing clinical guidelines and recommendations for this age group. The ambitious Thrombolysis in Pediatric Stroke (TIPS) trial had to be terminated prematurely due to poor patient enrolment. This review critically looks at the current status of the acute management of ischemic strokes in children with a specific emphasis on thrombolytic therapy. Until we have better evidence-based guidelines for this age group, it will be prudent to develop robust institutional pathways to provide this important intervention for all eligible children with acute strokes.

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Background: There has been an increase an alarming rise in invasive mycoses during COVID-19 pandemic, especially during the second wave. Aims: Compare the incidence of invasive mycoses in the last three years and study the risk factors, manifestations and outcomes of mycoses in the COVID era. Methodology: Multicentric study was conducted across 21 centres in a state of western India over 12-months. The clinico-radiological, laboratory and microbiological features, treatment and outcomes of patients were studied. We also analysed yearly incidence of rhino-orbito-cerebral mycosis. Results: There was more than five-times rise in the incidence of invasive mycoses compared to previous two-years. Of the 122 patients analysed, mucor, aspergillus and dual infection were seen in 86.9%, 4.1%, and 7.4% respectively. Fifty-nine percent had simultaneous mycosis and COVID-19 while rest had sequential infection. Common presenting features were headache (91%), facial pain (78.7%), diplopia (66.4%) and vison loss (56.6%). Rhino-orbito-sinusitis was present in 96.7%, meningitis in 6.6%, intracranial mass lesions in 15.6% and strokes in 14.8%. A total of 91.8% patients were diabetic, while 90.2% were treated with steroids during COVID-19 treatment. Mortality was 34.4%. Conclusion: Invasive fungal infections having high mortality and morbidity have increased burden on already overburdened healthcare system. Past illnesses, COVID-19 itself and its treatment and environmental factors seem responsible for the rise of fungal infection. Awareness and preventive strategies are the need of hours and larger studies are needed for better understanding of this deadly disease.

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Background: Governments have imposed lockdowns in the wake of the COVID-19 pandemic. Hospitals have restricted outpatient clinics and elective services meant for non-COVID illnesses. This has led to patients facing unprecedented challenges and uncertainties. This study was carried out to assess patients' concerns and apprehensions about the effect of the lockdown on their treatments. Materials and Methods: An ambispective, observational cross-sectional single centre study was conducted. Patients were contacted telephonically and requested to answer a structured questionnaire. Their responses were documented and summarized as frequency and proportions. Results: A total of 727 patients were interviewed. Epilepsy (32%) was the most common neurological illness in our cohort followed by stroke (18%). About half the patients and/or their caregivers reported health-related concerns during the lockdown. The primary concern was how to connect with their treating neurologist if need arose. Forty-seven patients (6.4%) had drug default. Among patients on immunomodulatory treatments, only eight patients had drug default. High compliance rates were also observed in the stroke and epilepsy cohorts. Of the 71 patients who required emergency care during the lockdown, 24 could reach our hospital emergency. Fourteen patients either had a delay or could not seek emergency care. Two-thirds of our patients found the telemedicine experience satisfactory. Conclusion: The ongoing pandemic will continue to pose challenges to both physicians and patients. Patients in follow-up may need to be contacted regularly and counselled regarding the importance of maintaining drug compliance. Telemedicine can be used to strengthen the healthcare delivery to patients with non-COVID illnesses.

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Wilson's disease (WD) is an autosomal recessive disorder due to ATP7B gene mutation, resulting in defective copper metabolism, with liver and brain being primarily affected. Being a treatable disorder, early diagnosis and proper management of WD may result in near complete recovery. It has received significant attention over the past 50 years, with several Indian contributions. This study collates published Indian studies on WD in Pubmed and Embase databases and puts them in perspective. Several Indian case series suggest that WD may be more prevalent than thought. Commonly detected ATP7B mutation in India is p.C271X. Although initial Indian series reported significant osseomuscular presentation, neuropsychiatric and hepatic manifestations dominated the later reports. A significant male predominance is observed in Indian series. Pure hepatic presentation starts earlier than neurological or osseomuscular WD. A positive family history may be seen in nearly 50% of Indian WD cases with a high rate of consanguinity. Up to two-third of Indian cases may be initially misdiagnosed, with a mean diagnostic delay of up to 2 years. Abnormalities in serum ceruloplasmin and 24-hour urinary copper has been reported in more than four-fifth cases. Brain MRI is abnormal in nearly all neurological WD cases. Copper chelation remains the mainstay of therapy, with D-penicillamine being the most widely used chelator in India. Global Assessment Scale for WD is a comprehensive tool for clinical monitoring. Hepatic presentation carries a five-time higher mortality risk than neurological, with up to 90% Indian neurological WD cases recovering to pre-morbid functionality with adequate therapy.

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Idiopathic generalized epilepsies (IGEs) are a group of epilepsies characterized by an underlying genetic predisposition and a good response to antiseizure medicines (ASMs) in the majority of the patients. Of the various broad-spectrum ASMs, valproate is the most effective medicine for the control of seizures in IGEs. However, with the availability of many newer ASMs and evidence showing the high teratogenic potential of valproate, the choice of ASMs for IGEs has become increasingly difficult, especially in women of the child-bearing age group. In this article, we review the current evidence regarding the efficacy and safety of various ASMs in patients with IGEs and provide practical guidelines for choosing appropriate ASMs in various subgroups of patients with IGEs.

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Deep brain stimulation (DBS) can lead to psychosocial and functional improvement in medically refractory cervical, segmental, or generalized moderate to severe dystonia. After treatment with DBS in women with dystonia, pregnancy can be planned. However, in the literature, there are no standardized clinical guidelines for the management of movement disorder treated with DBS during pregnancy. Herein, we report a 24-year-old female patient with cervical dystonia (CD) who have an implanted bilateral globus pallidus interna (GPi)-DBS. The patient got pregnant during the 5-year follow-up period after DBS surgery and then delivered a healthy baby via cesarean section under general anesthesia. A patient with CD who have a DBS system with a rechargeable battery could be managed safely during pregnancy and childbirth.

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Background: Previous researchers have used a 30-min eutectic mixture of local anesthetic (EMLA) test, which assesses the sympathetically mediated vasomotor function, in diagnosing carpal tunnel syndrome (CTS). However, its specificity was low, limiting its clinical diagnostic utility. In this study, we assessed the efficiency of 90-min extended EMLA-induced stimulated skin-wrinkling (SSW) test in CTS diagnosis. Methods: A cross-sectional study was designed among patients clinically diagnosed with CTS. Hands of healthy volunteers and the asymptomatic hands of selected patients served as control. The Boston symptom severity scale (SSS) and the neuropathic pain severity inventory (NPSI) were used to assess symptom severity, and nerve conduction study (NCS) was used to assess electrophysiological severity. EMLA-induced SSW was visually graded after 90 min of application and correlated with symptom and NCS severities. Results: Forty-two symptomatic hands and 30 asymptomatic hands were enrolled as cases and controls, respectively. The diagnostic efficiency of the extended EMLA test was found to be 83.4% for digit 2 and 87.3% for the lateral 4 digits (mean), whereas the diagnostic efficiency of standard NCS was 88.1%. Boston SSS and NPSI were better correlated with EMLA positivity than NCS positivity. A linear regression analysis showed negative correlation of wrinkling grade with NCS grade. Conclusion: With its improved diagnostic efficiency, the 90-min extended EMLA test can feasibly be used as an alternative to NCS, especially in general practice settings. Its potential clinical utility should be explored in a large population of CTS patients showing varying clinical and electrophysiological severities.

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Background: PON1 is an High Density Lipoprotein (HDL)-associated esterase. Two common polymorphisms in the PON1 gene, Q192R and L55M substitutions, determine the inter-individual variation in PON1 activity. The association of these polymorphisms with the risk of ischemic stroke remains controversial. In the present study, the role of PON1 Q192R gene polymorphism in ischemic stroke was studied in the Indian population. Design and Methods: In the present case-control study, the PON1 Q192R gene polymorphism was screened in ischemic stroke patients (n: 63) and age, sex-matched controls (n: 63) using the Polymerase Chain Reaction-Restriction Segment Length Polymorphism (PCR-RFLP) method. Results: The mean age of stroke presentation was 58.11 ± 15.4 years. A total of 17.4% cases presented with young stroke (<45 years age) and 9.52% cases were seen to have a recurrent stroke. The distribution of -192Q/R PON1 gene polymorphism was not seen to differ between cases and controls. The traditional stroke risk factors did not have any effect on the PON1 genotype expression. A multivariate logistic regression analysis was done in order to assess an independent association of age, gender, traditional stroke risk factors, and PON1 polymorphism with acute ischemic stroke. However, neither the RR genotype nor the presence of the R allele was associated with an increase in the risk of acute ischemic stroke (OR [RR genotype]-4.76, P value: 0.24, 95% CI: 0.3497–64.8531; OR [R allele]-0.94, P value: 0.90, 95% CI: 0.3516–2.4989). Conclusion: PON1 Q192R gene polymorphism is not associated with an increased risk of acute ischemic stroke in the North Indian population. Further studies with a larger sample size are needed before PON1 Q192R gene polymorphism can be considered as a genetic risk factor for ischemic stroke.

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Background: Headache is a frequently encountered symptom among patients undergoing hemodialysis. Aim: The aim of this study was to elucidate the prevalence of hemodialysis associated headache (HDH), its possible etiology, its effect on the patients and steps taken in the management of the condition in Indian patients with end-stage renal disease (ESRD). Methods and Materials: A cross-sectional study was carried out amongst 128 consenting patients with ESRD on regular hemodialysis at a tertiary care medical teaching hospital over a period of 3 months to assess for prevalence of HDH and factors related to it. The pre hemodialysis serum electrolytes level, pre and post hemodialysis systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded. Visual analogue scale (VAS) and patient health questionnaire-9 (PHQ9) was administered to the patients. t Test and Chi-square test were applied to find the association between HDH and various postulated factors and a regression analysis was performed. Results: Among 128 patients, 48 (37.5%) (men 18 [37.5%], women 30 [62.5%]) were found to have HDH. The mean headache severity scores on (VAS) was 4.5 ± 1.74. Patients having HDH had their mean PHQ9 scores 7.56 ± 4.51. Most patients had headaches in the first hour of dialysis and were located in the frontal and temporal part of the head. No statistically significant difference was found in the electrolyte levels between patients having HDH and without HDH. The headache was moderate in most but needed a paracetamol tablet to relieve the headache. Conclusion: Nearly one-third of patients undergoing dialysis have HDH, and it is associated with mild to moderate depression. The factors leading to HDH and its management need to be evaluated further to improve the quality of life of patients with ESRD on dialysis.

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Objective: The objective of the study was to determine incidence, risk factors, and short-term outcomes of young stroke in Ludhiana city, Northwest India. Methods: Data were collected on first-ever stroke in patients of age ≥18 years, from hospitals, diagnostic imaging centers, general practitioners, and municipal corporation during March 2011–March 2013 in Ludhiana city, using the World Health Organization Stepwise Approach to Surveillance (WHO STEPS). Outcome was documented using the modified Rankin Scale at 28 days. Results: Of 2948 patients, 700 (24%) were in the age group 18–49 years. Annual incidence in this age group was 46/100,000 person-years (95% confidence interval [CI], 41–51/100,000). Hypertension (84%), diabetes mellitus (48%), and atrial fibrillation (AF) (12%) were found more common in >49 years age group, as compared with 18–49 years age group. Drug abuse (8.7% vs. 6% in age >49 years; P = 0.04) and tobacco intake (8.7% vs. 5.6% in age >49 years; P = 0.02) was more common in young people, that is, 18–49 years age group in comparison to older patients, >49 years age group. Recovery was better in younger subjects (60% vs. 46% in age >49 years P < 0.001). In a multivariable analysis, younger people were more often literate (odds ratio [OR] 2.52; 95% CI, 1.68–3.77; P < 0.001), employed (OR 3.92; 95% CI, 2.20–5.21; P < 0.001), and 374 (60%) had good clinical outcome, modified Rankin Scale <2 at 28 days follow-up as compared with 938 (46%) older patients (OR 1.52; 95% CI, 1.15–2.00; P = 0.003). Conclusion: Hypertension, diabetes mellitus, drug addiction, and tobacco intake were significantly associated with young stroke. Outcome was also better in younger people.

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Levodopa (L-dopa) is the gold standard in the management of Parkinson's disease (PD). It dates back to 1500 to 1000 BC when it was used in the Indian Ayurvedic and Chinese system of medicine. Certain beans such as velvet beans and broad beans contain L-dopa. The plant Mucuna pruriens (Mp) or velvet bean, cultivated in Eastern India and Southern China, contains L-dopa at a concentration of 5% and was used for the management of PD. Later, workers have documented the neuroprotective, neurorestorative, and immunomodulatory properties of Mp. Double-blind studies conducted in the Western world have proved the efficacy of Mp and reported some toxic side effects as well. In the Western world, the credit for isolating L-dopa from the seeds of Vicia faba or broad bean goes to Markus Guggenheim, a biochemist from Sweden in 1913. However, it has been used with success ever since Arvid Carlsson established the reversibility of reserpine-induced akinesia in rabbits in the late 1950s with the use of intravenous dopamine, and Oleh Hornykiewicz demonstrated its deficiency in the striatum in 1960–1961. George Cotzias used it in patients in a low and slow incremental fashion in 1967, and Melvin Yahr and his colleagues performed double-blind study on in-patients with success in 1969. Complications with its long-term use, particularly the on-off phenomenon, and dyskinesias appeared soon, and measures have been undertaken to reduce their incidence. Researches on alternative modes of delivery are carried out in various centers, and others are under investigation in the laboratories.

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Background: Lipid storage myopathies (LSM) constitute an important group of treatable myopathies. Genetic testing is essential for confirming the diagnosis and also helps in explaining phenotypic heterogeneity. The objective of this study was to describe the clinical features and genetic spectrum of LSM seen in a quaternary referral center in India. Methods: Eleven cases of suspected LSM underwent clinical, biochemical, histopathological and genetic evaluation. Tandem Mass Spectrometry and clinical exome sequencing with Sanger validation were performed. Results: All patients had exertion induced myalgia and either progressive or episodic limb girdle muscle weakness (LGMW). The age of onset ranged 10 to 31 years (mean- 21 ± 6.7y), age at presentation- 14 to 49 years (mean- 26.5 ± 9.5y). Mutations identified: ETFDH = 5, CPT2 = 3, FLAD1 = 1, ACADVL = 1, PNPLA2 = 1. Dropped head syndrome was seen in two patients with ETFDH mutations. Bulbar symptoms and Beevor's sign were noted in a patient with FLAD1 variant. Novel variants were identified in seven patients. Conclusions: This is the first report on the genetic spectrum of LSM from India. LSM should be considered in patients with exertion induced myalgias, LGMW, cranial nerve involvement or dropped head syndrome. Genetic testing is essential for identification of these treatable disorders.

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Background: Headache is one of the commonly reported symptoms of coronavirus disease-2019 (COVID-19) illness. A number of studies have been done so far focusing on headache associated with COVID-19 with variable incidence and characteristics. Material and Methods: This study is a prospective study conducted on 120 patients with confirmed COVID-19 illness. Critically ill and ventilated patients were excluded. Demographic data, COVID illness symptom profile, headache characteristics were documented. Patients were followed up at 2 weeks and 4 weeks. For the statistical analysis, Statistical Package for the Social Sciences (SPSS), version 24.0 was used. Results: 120 COVID-19 positive cases were included in the study with a mean age of 54.59 ± 14.89 years (range 21-84 years) with male-to-female ratio of 3:2. 78.33% (94) of patients had various comorbidities. 43.33% (52) cases were diabetic. The presenting symptoms were fever (65%), cough (53.33%), shortness of breath (35%) and myalgia (31.66%). 26 (21.66%) patients reported headache during the COVID illness. 18 (15%) cases had headache attributed as secondary to COVID-19 illness. Out of them, 12 cases were new onset with no past history of headache and 6 cases had a significant change in previous headache episodes. COVID-19 illness precipitated headache episodes similar to past headache type in 8 cases. Headache was the presenting symptom in 8 (6.66%) patients with COVID-19 being detected in the regular hospital screening protocol. Conclusion: Headache was a common symptom in COVID-19 patients. New onset headaches or change in past headache type in patients in the setting of ongoing pandemic should be screened for COVID-19.

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Atherosclerosis at the carotid bifurcation in the neck is common and the result of turbulent hemodynamics in the bulb. Carotid bulb plaques cause disabling strokes. Carotid vessel wall imaging characterizes the atherosclerotic plaque, documents disease progression, and assesses lesion severity by plaque morphology in addition to the degree of stenosis. This in turn optimizes treatment selection for the individual patient. The aim of vessel wall imaging in patients of stroke is to distinguish stable plaques that may be conserved with best medical management from unstable or vulnerable plaques that require more aggressive medical treatment, carotid stenting, or carotid endarterectomy. Growing evidence suggests that depending on luminal stenosis measurements alone for management decisions will result in underestimating a number of plaques whose size may be small, but where the plaque morphology is unstable, there is a high likelihood of the patient developing a thromboembolic stroke in the near future. In today's context of aggressive management of even transient ischemic attacks and minor strokes, vessel wall imaging should be particularly performed in cryptogenic strokes without significant luminal narrowing on angiography to identify a subset of patients with nonstenotic but unstable atherosclerotic plaques that may be covert etiologies of stroke. If patients receiving the best medical management have recurrent strokes on the same side as a carotid plaque with “vulnerable” plaque features, they may deserve surgical or endovascular intervention even if they do not meet the conventional stenosis thresholds. Improved techniques for stroke imaging and consequent management have a remarkable effect in decreasing individual and public health burdens.

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