Annals of Indian Academy of Neurology
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   Table of Contents - Current issue
March-April 2020
Volume 23 | Issue 2
Page Nos. 145-241

Online since Wednesday, February 26, 2020

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National exit test: How will one size fit all? p. 145
Piyush Ranjan, Rajeev Ranjan, Mukul Kumar
Medical education in India is expected to undergo a significant reform after the introduction of the National Medical Commission Act. Single, nationwide National Exit Test (NEXT) is an essential provision under this act, which will be implemented during the next three years. It aims to bring about uniformity in the minimum standard of final MBBS examination, quality control in the licentiate examination and elimination of multiple entrance examinations for admission in postgraduate courses. Since the NEXT has multiple and varied objectives, we suggest a three-step scheme for the conduct of NEXT. Step I (Part A and B) will be equivalent to present-day first and second professional MBBS examinations and step II will act as the final professional MBBS and licentiate examination. Step III will form the basis for admission to the different PG courses. The written exam of Step I and II will consist of structured long, short and multiple choice type questions, whereas practical or clinical examination will consist of structured instruments with lesser inter-rater variability (viz., OSCE, OSPE, OSLER, etc.). This opinion piece is a result of in-depth discussions among major stakeholders such as MBBS students, resident doctors, and faculty of AIIMS, New Delhi. The suggested three-step plan is probably the most feasible way to ensure that the three modalities (final year MBBS, licentiate examination, and PG entrance competitive) are assessed in a valid, reliable, and acceptable manner. Due consideration is given to the fact that an assessment process has a significant impact on learning and teaching. The government may consider these suggestions while formulating the regulations of the NMC Act.
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Editorial commentary on the national exit examination p. 150
Kameshwar Prasad
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What NEXT for neurology education and assessment? p. 151
Apoorva Pauranik
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Phenotypic variability in huntington's disease p. 153
Anjali Chouksey, Sanjay Pandey
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Gut microbiota and stroke p. 155
Benjamin Y. Q. Tan, Prakash R Paliwal, Vijay K Sharma
Ischemic stroke remains a significant health problem, which is expected to increase owing to an aging population. A considerable proportion of stroke patients suffer from gastrointestinal complications, including dysphagia, gastrointestinal hemorrhage, and constipation. Often, these complications adversely affect stroke outcomes. Recent research postulates the role of “brain-gut axis” in causing gut microbiota dysbiosis and various complications and outcomes. In this review, we present our current understanding about the interaction between commensal gut microbiome and brain in determining the course of stroke.
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Idiopathic intracranial hypertension: The monster within p. 159
Aastha Takkar, Vivek Lal
Idiopathic intracranial hypertension (IIH) is defined as a syndrome of raised intracranial pressure with normal imaging of the brain and cerebrospinal fluid (CSF) composition. There are many controversies and myths that surround IIH. Although patients of IIH may present “typical” symptoms and signs of raised intracranial pressure, clinical scenarios often vary. A typical clinical and radiological finding poses significant problems in diagnosis and management of patients with IIH. We have tried to resolve these controversies and provide a comprehensive update on different aspects of IIH. In this article, we review the common problems encountered while dealing with patients of IIH.
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Functional language network connectivity in children of women with epilepsy with selective antenatal antiepileptic drug exposure p. 167
Ruma Madhu Sreedharan, Chandrasekharan Kesavadas, Subramonium Aiyappan, KM Anila, Amitha C Mohan, Sanjeev V Thomas
Purpose: Children of women with epilepsy and antenatal antiepileptic drug (AED) exposure have increased risk of language dysfunction. Our objective was to compare language related functional MRI network connectivity (FC) of children with women with epilepsy with antenatal AED exposure (CAED) with that of healthy children (COAED) for delineating functional basis of the language dysfunction. Methods: CAED under prospective follow up in Kerala Registry of Epilepsy and Pregnancy were consecutively sampled. COAED were identified from volunteers with normal brain MRI. Clinical Evaluation of Language Fundamentals score (CELF) was used to assess language. Functional MRI done using verb generation paradigm to activate language areas and key language network nodes were identified. A multivariate ROI-to-ROI and Seed-to-Voxel based FC was done using the selected seed regions in the language areas located in the right and left hemisphere in all subjects using the CONN functional connectivity toolbox in SPM8 under MATLAB. Results: Strong connectivity was observed within the identified language network between all language nodes bilaterally in CAED compare to controls. The mean connectivity strength of language network (LN) on the left side in CAED was 9.63 ± 4.62 (Mean ± SD) while for COAED it was 6.96 ± 3.67 (p=0.0001). The mean connectivity strength of LN between CAED (4.86 ± 1.07) and COAED (4.32 ±1.2) on the right hemisphere was not statistically significant (p=0.18). Conclusion: CAED with impaired language function had significantly increased functional connectivity which may indicate poor differentiation and localization of language centers.
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Levosulpiride-induced neurological adverse effects: A prospective study from a tertiary care center Highly accessed article p. 174
Jacob Joe
Background: Levosulpiride (LS) is a prokinetic drug increasingly used for the gastric motility disorders. Despite its common use for the gastric motility disorder, the tendency to cause parkinsonism and acute dystonias are under-recognized as the major adverse effects. This study was aimed to evaluate the adverse effects of this drug in patients attending neurology clinics. Methods: Patients presenting with new-onset extrapyramidal symptoms with respect to LS therapy were selected for the study. A detailed history had been taken using a questionnaire. All the patients were tested for neurological manifestations. The number of cases was then statistically analyzed. Results: A total of 30 patients were diagnosed with LS-induced movement disorders. The average age of patients was 65 ± 12 years with 17 males and remaining females. Major presentations were tremor, stiffness, dystonia, neck or back pain, dysarthria, and abnormal feelings. Stiffness, tremor, or both were among the most common signs. A statistically significant (P = 0.0154) positive correlation (r = 0.8295) was found between the duration of LS treatment and incidence of tremor/stiffness. Among them, 19 patients were started with dopaminergic drugs and five were given symptomatic measures. Six patients had no follow-up. Conclusion: The LS treatment was found to produce adverse effects such as tremor and stiffness. Early recognition of this condition is essential for its complete cure and better prognosis. Therefore, one should be cautious about the LS as one of the etiologies for acute recent-onset extrapyramidal syndromes while working up patients.
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Neuro-developmental and epilepsy outcomes of children with west syndrome: A cross-sectional study from North India p. 177
Juhi Gupta, Suvasini Sharma, Sharmila B Mukherjee, Puneet Jain, Satinder Aneja
Objectives: To assess the neurodevelopmental outcome of West syndrome (WS) in Indian children, who differ in their clinical profile from the western population. Materials and Methods: This cross-sectional study enrolled children aged 2--5 years with prior diagnosis of WS between November 2013 and March 2015. They were assessed for epilepsy outcome and developmental outcome using developmental profile 3 (DP3) and vineland adaptive behavioral scale II (VABS II). Results: Sixty-one children were enrolled. Perinatal asphyxia (40.9%), neonatal hypoglycemia (14.8%), and neonatal meningitis (9.8%) were predominant causes among the children with known etiology. Favorable epilepsy outcome (seizure freedom for >6 months) was observed in 29/61 patients (47.5%). Moderate to severe developmental delay was observed in 55/61 children (91.8%). Favorable developmental outcome (GDS by DP3 >70) was observed in just 5/61 (8%) patients. Conclusions: This study highlights the high prevalence of developmental delay in this population of children with WS, with adverse perinatal events being the most common etiology.
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Clinical, etiological and imaging profile of posterior reversible encephalopathy syndrome: A prospective and follow-up study p. 182
Saurabh Bansal, Ramandeep Bansal, Manoj Kumar Goyal, Aastha Takkar, Ramandeep Singh, Paramjeet Singh, Vivek Lal
Background: Although first described more than two decades ago, posterior reversible encephalopathy syndrome (PRES) continues to be enigmatic. We prospectively followed consecutive patients of PRES both clinically and radiologically for a better understanding of natural history, symptomatology, and prognosis of this not so uncommon entity. Patients and Methods: The current study included 22 consecutive patients of PRES who were followed both clinically as well as radiologically at a tertiary care institute in Northern India from December 2014 to June 2016. Results: Mean age was 30.68 ± 12.68 years. The most common symptoms included altered sensorium (77.3%), headache (72.7%), seizures (63.6%), vomiting (36.4%), and visual disturbances (22.7%). About 94.5% of patients had parieto-occipital signal changes on neuroimaging. Magnetic resonance imaging (MRI) (n = 20) revealed involvement of sites considered atypical for PRES in 95% (frontal [55%], temporal [40%], cerebellum [40%], basal ganglia [15%], deep white matter [10%] and brainstem [10%]). Diffusion restriction, haemorrhage, and contrast enhancement were seen in 30%, 22.2%, and 25% of patients. At 3 months follow-up, modified Rankin scale was 0 in 19 patients and 1 in 1 patient. Two (9.1%) patients died. Eight (36.4%) patients had eclampsia, 5 (22.7%) each had chronic kidney disease and essential hypertension whereas 2 (9.1%) each had immune-mediated disorders and drug-induced PRES. None of the clinical or imaging features predicted outcome in PRES. Conclusion: Atypical MRI presentations of PRES are common, and there is a need to keep a strong index of suspicion for the diagnosis of PRES. The prognosis of PRES is good, and most cases show excellent recovery, particularly if underlying etiology can be treated satisfactorily.
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Effect of age on arterial recanalization and clinical outcome in thrombolyzed acute ischemic stroke in CLOTBUST cohort p. 189
Arvind Sharma, Vijay K Sharma, Aftab Ahmad, Deepak Gupta, Khursheed Khan, Ashfaq Shuaib, Andrei V Alexandrov, Maher Saqqur
Background and Aims: Despite the evidence from randomized clinical trials, the effectiveness of intravenous tissue recombinant plasminogen activator (IV-tPA) for elderly patients (≥80 yrs) with acute ischemic stroke (AIS) is often an important consideration in clinical practice. We evaluated the effect of older age on arterial recanalization, timing of recanalization and outcome in thrombolysed AIS patients. Methods: Consecutive AIS patients treated with IV-tPA and transcranial Doppler (TCD) examination within 3 hours of symptom-onset were included. Thrombolysis in Brain Ischemia (TIBI) flow-grading system was used to interpret TCD findings of persistent occlusion, re-occlusion and complete recanalization within 2 hours of IV-tPA bolus. Poor functional outcome was defined by modified Rankin score of 3 or more. Univariate and multiple logistic regression analyses were performed to assess the effect of age on clinical and TCD outcome measures. Results: The study included 361 patients (elderly = 85, <80 yrs = 276). Median age was 68 years (range 18-91 years). Compared to the elderly, younger patients (<80 years) were more females (63.5% versus 41.3%), had higher baseline National Institute of Health Stroke Scale score (17.5 versus 16.0 points) and shorter time from symptom-onset to IV-tPA bolus (median 136.6 versus 139.7 minutes). No significant differences were noted between the site of arterial occlusion, TCD outcome measures or time of complete recanalization between the 2 groups. More patients aged < 80 years achieved good functional outcome (51.9% versus 31.8% in the older age group; P = 0.004). IV-tPA induced recanalization and symptomatic intracranial hemorrhage were similar in the 2 groups. Multivariate logistic regression showed elderly age as an independent predictor of poor outcome (adjusted OR 2.5, 95%CI 1.26-4.95; P = 0.008). Conclusion: Elderly AIS patients achieve relatively poor functional outcome after IV-tPA despite similar rates of arterial recanalization. However, there is no increase in the hemorrhagic risk. Perhaps, decision for IV thrombolysis in elderly patients should be made cautiously.
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“Clinical profile of genetically proven huntington's disease patients from Eastern India” p. 195
Zakir Hussain, Adreesh Mukherjee, Goutam Ganguly, Anindita Joardar, Sarnava Roy, Deb Sankar Guin, Uma Sinharoy, Atanu Biswas, Shyamal Kumar Das
Background and Aims: To study the clinical profile of genetically proven Huntington's disease (HD) patients from eastern India. Methods: This cross sectional study selected patients of HD after genetic confirmation of expanded CAG repeats in Huntingtin (HTT) gene. We performed detail clinical evaluation including cognitive and neuropsychological assessment, and imaging of brain. Results: This study included 75 patients (male: 57.3%; female: 42.7%). Mean age at onset was 37.12 (range 16-62) years; juvenile variety (onset below 20 years) was detected in 5.3%. Paternal transmission was commoner. Manifestations at onset were motor in 81.3% patients, behavioral in 10.7% and cognitive impairment in 8%. After chorea, next common movement disorder was dystonia. Frontal lobe dysfunction was found in 77.3% patients. Behavioral disturbances were observed in 77.3% patients and commonly manifested as depression, irritable behavior and anxiety. Among the three onset groups (motor/behavioral/cognitive), there was no significant difference regarding age at onset, gender distribution, pattern of inheritance (paternal/maternal), and at the time of evaluation, all groups had essentially similar pattern of clinical features. Mean CAG repeat of the patients was 48.25 (range 40-79). Our study showed some differing clinical characteristics compared to previous studies from the Indian subcontinent. Conclusion: Clinical features in our study showed differences from previous studies from the Indian subcontinent. We had more cognitive-onset patients. However, behavioral onset was lower in our study. Motor, behavioral and cognitive onset groups of HD were comparable regarding demographics, family history, CAG repeat lengths and major clinical features at the time of evaluation.
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Tolosa–Hunt syndrome: Long-term outcome and role of steroid-sparing agents p. 201
Anupriya Arthur, Ajith Sivadasan, Pavitra Mannam, AT Prabakhar, Sanjith Aaron, Vivek Mathew, M Karthik, Rohith Ninan Benjamin, Shaikh Atif Iqbalahmed, Gideon Lyngsyun Rynjah, Mathew Alexander
Background: Tolosa-Hunt Syndrome (THS) is one of the causes of cavernous sinus syndrome causing painful ophthalmoplegia. Literature on long-term outcome of this rare condition is scarce. Aims and Objectives: The aim is to study the recurrence and role of steroid-sparing agents in THS. Methodology: All cases of THS treated at a tertiary-level teaching hospital during a 10-year period were studied. Clinical and radiological profile, response to treatment and recurrences were noted. Results: A total of 44 cases were studied. The mean age was 49.5 years, Males constituted 23/44 (52%). The first symptom was pain in 90%. Ptosis with ophthalmoplegia was the most common deficit 29/44 (66%). Lesions confined to cavernous sinus 27/44 (61%) was the most frequent magnetic resonance imaging finding. All patients received steroids as the initial treatment and 15/44 (34%) received steroid-sparing agents. Follow-up ranged from 6 to 120 months (Mean 39 months). Two patients had alternative diagnosis of leptomeningeal malignancy and hypertrophic pachymeningitis on follow-up. Recurrences occurred in 18/37 (48.6%). Time for recurrence varied from 8 months to 7 years. (Mean 18 months). No clinical or radiological predictors for recurrence were identified. Patients who received steroid-sparing agents had a significantly lower recurrence 3/15 (20%) versus 14/26 (53.8%)P < 0.034. Conclusions: Around 50% of patients with THS can have recurrence. Steroid-sparing agents appear to prevent recurrence. A prospective multicenter randomized controlled trial may help to evaluate the risk and benefits of steroid-sparing therapy and to identify any possible predictors for recurrence.
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Identification of PCDH19 gene mutations/deletions in patients with early onset epilepsy p. 206
Semra Gursoy, Esra Ataman, Bahar Toklu Baysal, Berk Özyılmaz, Pınar Gençpınar, Ayşe Semra Hız, Uluç Yiş, Aycan Ünalp, Nihal Olgaç Dündar, Ayfer Ülgenalp, Derya Erçal
Background and Aims:PCDH19 gene, which encodes protocadherin 19, is associated with epilepsy and intellectual disability, mainly in affected females. The clinical manifestations are heterogeneous and the main features include early onset seizure, generalized or focal seizures sensitive to fever, and brief seizures occurring in clusters. The disorders exhibit a unique and unusual X-linked pattern of expression. We aimed to investigate PCDH19 mutations/deletions in patients with epilepsy and describe the clinical/molecular features. Methods: PCDH19 gene was analyzed in 35 Turkish female patients from 34 families with early-onset epilepsy via direct sequencing and multiplex ligation-dependent probe amplification analysis. Additionally, array comparative genomic hybridization analysis was performed in patients with whole gene deletion. Results: We identified 2 different heterozygous mutations in 2 unrelated probands (5. 7%) which were located in exon 1. Additionally, whole gene deletions were detected in dizygotic twin girls (5. 7%), who had distinct clinical features and the deletion was inherited from the unaffected father. The second twin suffered more severe clinical manifestations including autistic features, behavioral problems, mild-moderate mental retardation and seizures, which were under control with multidrug regimen when compared with the first twin. Conclusion: PCDH19 is a major causative gene in patients with epilepsy and further data is required to gain a better understanding of phenotype-genotype correlation. In addition to gene sequencing, deletion/duplication analysis will improve the molecular diagnosis in patients with clinical findings.
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Levodopa-responsive chorea: A review p. 211
Mark Farrenburg, Harsh V Gupta
Background: Chorea is one of the disabling movement disorders, and the number of drugs which can treat this disorder effectively is limited. Tetrabenazine and deutetrabenazine are the two drugs approved by the US-FDA for the treatment of chorea associated with HD. Levodopa can improve chorea in some disorders, and this review aims to provide information on the use of levodopa in chorea. Methods: A literature search was performed in February 2019 using the following terms “levodopa chorea,” “levodopa TITF-1,” levodopa brain-lung-thyroid syndrome,” and “levodopa Huntington's Disease.” The information regarding the etiology, outcome, and dose of levodopa was collected. Results: We found a total of 18 cases in the literature where the benefit was reported with levodopa. Majority of the cases were brain-thyroid-lung (BTL) syndrome (50%). Another 5 cases were HD (Huntington's Disease), one with PCH type 2 (Pontocerebellar hypoplasia type 2), one with meningovascular syphilis, and two patients with Sydenham chorea. The patients with BTL syndrome responded to a very low dose of levodopa. Discussion: This review suggests that levodopa has the potential to improve chorea in BTL syndrome while its use in chorea due to other disorders requires further study. BTL syndrome due to NKX2-1 mutation responded to levodopa while we did not find any case of chorea due to ADCY-5 mutation responding to levodopa.
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Disease severity assessment and short-term outcome in patients with myasthenia gravis p. 215
Deepthi Vemuri, Butchi Raju Garuda, S Gopi, T Sateesh Kumar, U Aruna Kumari
Background: Myasthenia gravis (MG) is an autoimmune disorder with a chronic fluctuating course. The outcome measures encapsulate disease severity, functional impact at diagnosis, and objective evaluation of clinical benefit from therapeutic interventions.Aims and Objective: To assess the disease severity, correlation between various outcome measures, and to evaluate the short-term outcome at 3 months and 6 months in a cohort of MG patients.Materials and Methods: Quantitative myasthenia gravis (QMG) score, myasthenia gravis composite (MGC) score, and myasthenia gravis quality of life-15 (MG-QoL-15) score were applied to 54 patients at first visit, 3 months and 6 months follow-up.Results: Mean quality of life-15 (QoL-15) score at base line was 15.241. Mean QMG and MGC scores at baseline were 14.63 ± 8.37 and 15.87 ± 9.14, respectively. QMG score showed a strong positive correlation with both MGC and MG-QoL-15 scores. QMG and MGC scores showed a moderate correlation with acetylcholine receptor antibody (AChR Ab) titers. Mean QMG at follow-up was 9.95 ± 5.49 at 3 months and 6.74 ± 4.74 at 6 months. Mean MGC at follow-up was 10.75 ± 5.58 at 3 months and 6.51 ± 4.36 at 6 months. Conclusion: The combination of physician-evaluated and patient-reported outcome measures provided a more discerning picture of patient status and response to treatment. Incorporating MG outcome measures into clinical practice would aid in modulating therapies.
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Successful treatment of human immunodeficiency virus-associated highly active antiretroviral therapy-resistant vacuolar myelopathy with intravenous immunoglobulin p. 220
Lidiia N Prakhova, Aleksandr G Ilves, Svetlana N Kizhlo, Zhanna I Savintseva
For the first time, human immunodeficiency virus (HIV)-associated vacuolar myelopathy (VM) was detailed in an autopsy-based study of 89 cases in 1985. This condition is the most common cause for spinal cord lesions in HIV patients. VM's pathogenic mechanism remains unclear; however, it is assumed that the disease can be related to both, the direct neurotoxic impact of the HIV and HIV-induced activation of immunopathological processes in the central nervous system (CNS). Reviewed in this paper is a case where the VM presentation deteriorated drastically when treated with highly active antiretroviral therapy, and almost completely regressed after the patient received the intravenous immunoglobulin (IVIg) treatment. The considered case demonstrates the viability of IVIg treatment in patients with HIV-associated CNS pathology, particularly when autoimmune reactions are suspected. The results of placebo-controlled studies of IVIg in patients with HIV-associated myelopathy may give a reliable evaluation of IVIg use in this context.
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Chorea and parkinsonism with elevated striational antibody p. 223
Harsh V Gupta, Heather Barnes, Fatma A Radhi, Yasir Jassam
Subacute onset of a mixed movement disorder should alert the clinician to the possibility of an autoimmune or paraneoplastic cause of symptoms. Striational antibodies have been associated with myasthenia gravis but a mixed movement disorder has been rarely reported with this antibody. We report a 90-year-old female who presented with generalized chorea, blepharospasm, and parkinsonism. Extensive evaluation was done which showed an elevation in striational antibody and there was no evidence of malignancy. The patient responded dramatically to intravenous steroids. We suggest that striational antibody should be routinely tested as a part of the work-up for autoimmune or paraneo lastic movement disorder. The presence of chorea in a very elderly patient should not be dismissed as “senile chorea” and a search for treatabl etiology should always be performed.
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Anti-N-methyl-D-aspartate receptor encephalitis: Case series of psychiatric presentations p. 225
Arpit Koolwal, Supriya Agrawal, Ghanshyam Das Koolwal, Kaveri Saxena, Ankit Daral
Anti-NMDAR encephalitis is an autoimmune encephalitis with a typical clinical progression. Patients can often present to psychiatric outpatient departments (OPDs) mimicking psychiatric illnesses. In this case series, we have described two cases of adolescent age group that were eventually diagnosed with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. They had presented to psychiatry OPD and were admitted to the psychiatry ward. Both cases had predominantly, although varied, psychiatric symptoms with a variable course, response to treatment and prognosis. We have tried to speculate if initial presentation in anti-NMDAR encephalitis can be suggestive or can predict response to treatment and prognosis in a patient. We advocate a high degree of suspicion for psychiatrists toward patients presenting acutely in the first episode of mania or psychosis, particularly in adolescent age group.
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Kawasaki disease complicated with cerebral vasculitis and severe encephalitis p. 228
Vesna D Stojanovic, Tanja D Radovanović, Katarina M Koprivšek, Gordana V Vijatov Ðurić, Aleksandra D Doronjski
We report a case of a 7-year-old boy with Kawasaki disease (KD) complicated with cerebral vasculitis and encephalitis. The patient was admitted with signs of encephalopathy, seizures, and coma. The diagnosis of KD was made on the 2nd day of hospitalization based on the clinical features (fever >5 days, maculopapular rash, nonpurulent conjunctivitis, fissured lips, and cervical adenopathy). Brain magnetic resonance imaging findings suggested cerebral vasculitis. Treatment with intravenous immunoglobulin was followed by mild improvement. After a single dose of immunoglobulin, pulse methylprednisolone therapy was started resulting in gradual improvement of consciousness and eventual complete motor and cognitive function recovery with regression of brain magnetic resonance lesions. KD can present with marked neurological symptomatology. Therefore, it should be considered in the differential diagnosis of encephalitis and encephalopathy etiologies in children.
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Vitamin D deficiency and its correlates in migraine patients p. 233
Jong-Geun Seo, Sung-Pa Park
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Bilateral INO in PSP p. 235
Harsh V Gupta, Kayla Karlowski, Thomas J Whittaker
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Acute flaccid myelitis caused by Japanese encephalitis virus: A rare association Highly accessed article p. 237
Nishanth Dev, Rahul Kumar, Ashok Kumawat, Mithu Bhowmick
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Epilepsy and hydrocephalus: Should pyridoxine-dependent epilepsy cross our minds? p. 239
Shivan Kesavan, Bhanudeep Singanamalla, Dangudubiyyam Sri Krishna Sahitya, Arushi Gahlot Saini, Sameer Vyas
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