Annals of Indian Academy of Neurology
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   Table of Contents - Current issue
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October-December 2019
Volume 22 | Issue 4
Page Nos. 369-545

Online since Friday, October 25, 2019

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EDITORIAL COMMENTARY  

Seronegative autoimmune encephalitis – A diagnostic and therapeutic dilemma p. 369
M Netravathi
DOI:10.4103/aian.AIAN_485_19  
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Plasmapheresis for NMOSD: Not a rescue therapy anymore!? p. 371
Rohit Bhatia, Radhakrishna Pedapati, Siddharth Chopra
DOI:10.4103/aian.AIAN_498_19  
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VIEW POINT Top

Critical appraisal of guidelines for evaluation and certification of specified neurological disabilities p. 373
Inder Puri, Govind Singh, Rajendra Kumar Acharya, Divya Goswami
DOI:10.4103/aian.AIAN_165_19  
New disability law called “Rights of Persons with Disabilities Act 2016” has been acted in 2016. The United Nations' Convention for Rights of Persons with Disabilities is the sole of this new act. Of the total 21 categories, three new neurological legal disability categories such as chronic neurological conditions, Parkinson disease (PD), and multiple sclerosis have been notified first time in the new act. The new guidelines have been notified in the year 2018 for evaluation and certification of specified disabilities. As a new addition in these guidelines, modified Rankin scale score has been added to measure locomotor disability of stroke. Certainly, newer guidelines have many lacunae also. There are no recommendations of any method of disability measurement associated with movement disorders such as PD, chronic neurological conditions such as migraine, epilepsy, and ataxia. The tables of older guidelines for disability calculation in conditions such as unconsciousness and epileptic fits have been removed in newer guidelines. Professional bodies should come into action immediately and do effort for rectifying these shortcomings and/or fallacies in new guidelines.
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SYSTEMATIC REVIEW Top

Diagnostic utility of human leukocyte antigen B*15:02 screening in severe carbamazepine hypersensitivity syndrome p. 377
Youssef Moutaouakkil, Badr Adouani, Yahia Cherrah, Jamal Lamsaouri, Yassir Bousliman
DOI:10.4103/aian.AIAN_492_18  
Background: Despite many studies suggesting an association between human leukocyte antigen (HLA)-B*15:02 and carbamazepine (CBZ)-induced severe cutaneous adverse drug reactions essentially toxic epidermal necrolysis (TEN) and Stevens–Johnson syndrome (SJS), the evidence of association in different populations and the degree of association remain uncertain. Materials and Methods: The primary analysis was based on population control studies. Data were pooled by means of a random-effects model, and sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR−), diagnostic odds ratios (DOR), and areas under the summary receiver operating characteristic curve (AUC) were calculated. Results: In 23 population control studies, HLA-B*15:02 was measured in 373 patients with CBZ-induced TEN/SJS and 3452 patients without CBZ-induced TEN/SJS. The pooled sensitivity, specificity, LR+, LR−, DOR, and AUC were 0.67 (95% confidence interval [CI] = 0.63–0.72), 0.98 (95% CI = 0.98–0.99), 19.73 (95% CI = 10.54–36.92), 0.34 (95% CI = 0.23–0.49), 71.38 (95% CI = 34.89–146.05), and 0.96 (95% CI = 0.92–0.98), respectively. Subgroup analyses for Han Chinese, Thai, and Malaysian populations yielded similar findings. Specifically, racial/ethnic subgroup analyses revealed similar findings with respect to DOR for Han Chinese (99.28; 95% CI = 22.20–443.88), Thai (61.01; 95% CI = 23.05–161.44), and Malaysian (30; 95% CI = 7.08–126.68) populations, which are similar to the pooled DOR for the relationship between the HLA-B*15:02 allele and CBZ-induced TEN/SJS across all populations (71.38; 95% CI = 34.89–146.05). Conclusions: The present study reveals that CBZ is the leading cause of TEN/SJS in many countries. Screening of HLA-B*15:02 may help patients to prevent the occurrence of CBZ-induced TEN/SJS, especially in populations with a higher (≥5%) risk allele frequency.
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HISTORY OF MEDICINE Top

William osler and harvey williams cushing: Friendship around neurosurgery p. 384
Marleide da Mota Gomes
DOI:10.4103/aian.AIAN_199_19  
William Osler was a mentor for the younger William Harvey Cushing and they intermingled careers and friendship for the rest of their lives. They shared a common interest in the anatomy and pathology of neurological disorders, and in the history of medicine. Their behavior was, however, sharply different: Osler was the revered physician, full of wisdom and good humor, and Cushing, the prestigious surgeon, in a perennial and successful struggle to improve neurosurgery and himself. Both became medical icons, one beloved, and the other admired, each praised at their death centennial and 150 birth anniversary, respectively.
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ORIGINAL ARTICLES Top

Plasma exchange as a first line therapy in acute attacks of neuromyelitis optica spectrum disorders p. 389
BL Kumawat, Reenu Choudhary, CM Sharma, Deepak Jain, Ashwini Hiremath
DOI:10.4103/aian.AIAN_365_19  
Background and Aims: Neuromyelitis optica spectrum disorder (NMOSD) is a demyelinating disorder of central nervous system with deleterious effects. At present Intravenous corticosteroids are used for the relapse as the first line of treatment, but with only a class evidence III-IV. Having an underlying humoral immune mechanism in the pathogenesis of NMOSD and as it is rightly said that “Time is Cord and Eyes”, delaying the time to start plasma exchange (PLEX) awaiting favorable outcome in response to corticosteroids is detrimental for the patient. Hence, PLEX may be a promising first line therapeutic approach in the management of severe attacks of NMOSD. The aim of this study is to evaluate the efficacy of PLEX as the first line of treatment for the acute attacks in patients with NMOSD that is being largely used as an add-on therapy for more than 10 years, and also to define the time opportunity window for the starting of PLEX. Methods: The study analysed the therapeutic efficacy and safety profile of PLEX as a first line therapy in 30 patients diagnosed with NMOSD over a period of 30 months. PLEX was performed using a Hemonetics Mobile Collection System plus machine with due written consent including the risks and benefits of the treatment that is being proposed to the patient/relative in their own language. Results: A total of 30 patients were analysed, out of which 16 were females and rest males. 85% of the patients were in the age group of 25-35 years. All the patients had severe Expanded Disability Status Scale (EDSS) scores at the baseline, and 73.33% showed significant improvement following PLEX. The only predictor of good outcome was the time to PLEX i.e shorter delay betters the outcome. Conclusion: The study ascertained the importance of early PLEX as a therapeutic intervention in severe attacks of NMOSD irrespective of their Anti-Aquaporin 4 (AQP4) antibody status.
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Epidemiologic features, risk factors, and outcomes of respiratory infection in patients with acute stroke p. 395
Lunlin Mao, Xiaobo Liu, Peng Zheng, Saiping Wu
DOI:10.4103/aian.AIAN_212_18  
Objective: The objective of this study is to explore risk factors for stroke-associated pneumonia (SAP) and their impact on prognosis. Materials and Methods: The data collected from a retrospective review of 257 patients with acute cerebral infarction between January 2014 and December 2016 were included in this study. Data were collected for clinical, demographic, and coexisting parameters. Univariate and multivariate logistic regression analyses were performed. Results: Elderly age (odds ratio [OR]: 1.096, 95% confidence interval [CI]: 1.023–1.174), dysphagia (OR: 2.805, 95% CI: 1.614–4.875), and long-term bedridden status (OR: 120.425, 95% CI: 29.689–488.466) were significantly associated with SAP. Among these risk factors, long-term bedridden status had the highest prognostic value (area under the curve = 0.908) for developing SAP. Furthermore, pneumonia, in turn, strongly predicted poor prognosis at discharge and after 3 years. Conclusions: Pneumonia seems to be a major complication in stroke patients. A better understanding of its risk factors is important for prevention and early recognition. Further studies are needed to clarify the optimal preventive treatment for SAP patients.
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Antibody negative autoimmune encephalitis- Does it differ from definite one? Highly accessed article p. 401
Sunil Pradhan, Animesh Das, Ananya Das, Madhura Mulmuley
DOI:10.4103/aian.AIAN_206_19  
Context: Autoimmune encephalitis (AE) is an emerging cause of non-infective encephalitis, presentations of which vary widely. Traditionally the diagnosis of AE is based on detection of antibodies in a patient with clinical picture suggestive of AE. Aim: To evaluate the clinical characteristics and response to immunotherapy in patients with antibody negative autoimmune encephalitis and to compare them with definite cases. Settings and Design: A prospective follow-up study was done in patients presenting with presumptive symptoms of AE from January 2017 to January 2019. The study was done in a tertiary care institute of Northern India. Patients and Methods: Demographic and clinical parameters were noted and relevant investigations for management were done according to well-defined protocol. The patients were treated with immunomodulatory therapy in the form of steroids and/or intravenous immunoglobulins (IVIg). They were followed up for treatment response and relapse at 2 monthly intervals. Statistical Analysis Used: The data was expressed as either proportions or mean/median. Chi-square test/Independent T test was used to compare antibody positive and antibody negative group. Results: Out of 31 patients with presumptive AE, 16 patients tested positive for autoimmune antibodies (definite AE). Incidences of seizure, behavioral abnormalities, dementia and altered sensorium were similar between the 2 groups (p > 0.05). Complete or partial response was seen in all treated patients in both groups with no significant difference (p 0.716). CSF protein concentration and cellularity were higher in the definite group although only high protein concentration could reach statistical significance (p 0.002). Malignancy could be confirmed after extensive search in 2 out of 16 patients with definite AE and in 1 out of 15 antibody negative AE patients. Conclusions: Clinical presentation of antibody negative cases does not differ significantly from definite ones. Since treatment response is also similar in both the groups, starting immunotherapy in a patient presenting with presumptive symptoms of AE, while ruling out other common mimickers, seems to be the need of the hour in the management of this evolving entity.
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Is dementia in Parkinson' disease related to chronic stress, anxiety, and depression? p. 409
Anita Pal, Nishi Pegwal, Madhuri Behari, Ratna Sharma
DOI:10.4103/aian.AIAN_341_18  
Objectives: Stress, anxiety, and depression are known to be associated with the development of neurodegenerative disorders through interactions with the underlying pathophysiology. We hypothesized that the presence of these symptoms contributes to cognitive disturbances and dementia in Parkinson's disease (PD). The present study aimed to investigate the levels of stress, anxiety, and depression in PD patients relative to healthy individuals. Materials and Methods: Anxiety, stress, and depression levels were assessed using standardized questionnaires in PD without dementia (PDND, n = 30), PD with dementia (PDD, n = 28), and healthy controls (HC, n = 26). Arithmetic subtraction task was used as a stressor. Galvanic skin response, heart rate and salivary cortisol, and alpha-amylase were measured during baseline and after induced stress (arithmetic task). Results: Acute anxiety, acute stress, and depression levels were significantly higher in PDND compared to HC, whereas both acute and chronic anxiety, stress, and depression levels were significantly higher in PDD compared to PDND and HC. Cortisol and alpha-amylase levels were significantly higher in PDND compared to HC during both baseline and postarithmetic task. Posttask levels of cortisol were lower in PDD compared to PDND. Conclusion: This study concludes that higher levels of salivary cortisol and alpha-amylase at baseline and poststress task with normal levels of chronic stress and anxiety were associated with no dementia in PD. Presence of higher levels of acute, chronic anxiety, and stress along with depression with lower cortisol reactivity to stressor suggests onset of dementia in Parkinson's patients.
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Lateralized periodic discharges are predictive of seizures in patients with intracerebral hemorrhage p. 414
Sushma Yerram, Nakul Katyal, Aarti Sarwal, Pravin George, Christopher R Newey
DOI:10.4103/aian.AIAN_154_18  
Background: Patients with intracerebral hemorrhages (ICHs) have higher incidence of seizures. Previous studies have suggested that location and size of hemorrhage may increase epileptogenicity. We aim to evaluate seizure development risk factors from clinical examination, imaging, and continuous electroencephalography (cEEG) in critically ill patients with ICH. Methods: We reviewed 57 consecutive patients with ICH admitted to a neurocritical intensive care unit over a 24-month period who were monitored on cEEG. Their demographic and examination data, ICH score, Glasgow Coma Scale (GCS), location of bleed, cEEG patterns, and discharge status were analyzed. Results: Sixteen (28%) patients from our study cohort had seizures at a mean duration of 7.46 h from cEEG hookup. Fifteen (93%) of those patients had only electrographic seizures. The finding of lateralized periodic discharges (LPDs) was significantly (P = 0.019) associated with seizures. Other variables, such as ICH score, size and location of hemorrhage, GCS, mental status, and other cEEG patterns, were not significantly associated with seizures. Conclusion: We found that LPDs were predictive of seizures in ICH patients. cEEG for longer than 24 h is preferred for detection of seizures as they occurred at a mean later than 7 h and most were without clinical signs.
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Evaluation of symptoms of depression and anxiety in adolescents with epilepsy in a tertiary-level medical center in Serbia p. 419
Ksenija Ervin Gebauer-Bukurov, Zeljka Dragomir Nikolasevic, Dragica Stevan Hajder, Zeljko Dragan Zivanovic, Vojislava Vojislav Bugarski Ignjatovic
DOI:10.4103/aian.AIAN_239_18  
Backgrounds: Even though epilepsy is the most common neurological disorder in adolescence; studies of adolescents with epilepsy are scarce. Objective: To evaluate whether adolescents with epilepsy are more likely to develop anxiety and depressive symptoms than their healthy peers and to determine the relationship of depression and anxiety scores to epilepsy-related variables. Settings and Design: Cross-sectional observational study. Methods and Procedures: Ninety adolescents with epilepsy aged 13-19 years were compared with healthy controls using the Beck Depression Inventory II (BDI II) and the Stait Trait Anxiety Inventory (STAI) for assessment of depressive and anxiety symptoms. Within the study group, epilepsy-related variables were also determined using the stated measures. Statistical Analysis Used: The independent sample t-test, One-Way ANOVA, Pearson's correlation coefficient. Outcomes and Results: 23.3% of the study group and 8.3% of the control group had mild to moderate depression. The mean BDI II score was significantly higher in the group of adolescents with epilepsy. Comparing the STAI scores, results on both STAI scales were higher in the study group. Regarding the epilepsy-related variables, a high frequency of seizures, symptomatic etiology and polytherapy showed strong associations with high depression and anxiety scores. Conclusion and Implications: Symptoms of depression and anxiety are not uncommon among adolescents with epilepsy. BDI II and STAI may be used as screening tools to provide useful information to clinicians when assessing adolescents' mental status.
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Abnormal subcortical volumes and cortical thickness in Parkinson's disease with impulse control disorders p. 426
Shweta Prasad, Venkateswara Reddy Reddam, Albert Stezin, Ravi Yadav, Jitender Saini, Pramod Kumar Pal
DOI:10.4103/aian.AIAN_325_18  
Background: The occurrence of impulse control disorders (ICDs) in Parkinson's disease (PD) is frequently attributed to dopamine replacement therapy. However, not all patients who receive medication develop ICDs. Recent imaging studies have suggested specific neuroanatomical abnormalities in patients with PD and ICD. Objectives: This study aims to identify changes in volumes of subcortical structures and cortical thickness specific to patients with PD and ICDs. Methodology: A total of 11 patients with PD and ICD (PDICD(+)), 15 patients with PD without ICD (PDICD(−)), and 15 healthy controls were analyzed in this study. ICDs were diagnosed and quantified using the Questionnaire for Impulsive-Compulsive Disorders in PD-Rating Scale (QUIP-RS). Structural imaging was performed on a 3T scanner; volumes of subcortical structures and cortical thickness were obtained using first in FSL and FreeSurfer. Results: Significant volume loss of the nucleus accumbens was observed in the PDICD(+) group. Several areas of significant cortical thinning were observed in the PDICD(+) group in comparison PDICD(−) group. Thinning of the left middle temporal gyrus, transverse temporal gyrus, and bilateral temporal poles was observed in the PDICD(+) group. No correlations were observed between QUIP-RS scores and areas of cortical thinning. Conclusions: The PDICD(+) group has specific neuroanatomical variations in the nucleus accumbens and temporal lobes, which may contribute to the development of ICD and perhaps predispose a patient to ICDs on exposure to dopamine replacement therapy.
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Urinary symptoms in patients with Parkinson's disease and progressive supranuclear palsy: Urodynamic findings and management of bladder dysfunction p. 432
Anupam Gupta, UK Rashmi Krishnan, Sushruth Nageshkumar, Pramod Kumar Pal, Meeka Khanna, Arun B Taly
DOI:10.4103/aian.AIAN_6_18  
Objective: The objective of this study is to observe urinary symptoms in patients with Parkinson's disease (PD) and progressive supranuclear palsy (PSP) and advice bladder dysfunction management based on urodynamic study (UDS) findings. Patients and Methods: Twenty-two patients (12 males) with PD and PSP (15 and 7, respectively) with urinary symptoms were included in this study. All patients except one were on levodopa and carbidopa medication. UDS was performed, and bladder management determined. Results: Mean age was 60.4 years (range 41–73 years, standard deviation [SD] 8.4). Mean illness duration was 31.9 months (range 9–146 months, SD 31.0) and mean duration of urinary symptoms was 14.8 months (range 1–61 months, SD 15.8). Eighteen patients reported nocturia and 16 patients had urgency with or without urge incontinence. Three patients had retention and straining to void and 3 had mixed urinary complaints. Twelve out of 22 patients had absence of voluntary anal contraction on per-rectal examination. UDS was suggestive of 12 patients with neurogenic detrusor overactivity with or without sphincter dyssynergy. Six patients had normal detrusor pressure, and four patients were found to have contractile detrusor. Ten patients had significant postvoid residual. Bladder management included pharmacotherapy, supportive, and behavioral management as appropriate. Conclusions: Patients with PD/PSP are known to develop urinary symptoms during illness. Clinical complaints and UDS findings do not necessarily match. UDS is required to manage urinary symptoms. Most of the patients respond to oral antimuscarinic medications along with behavioral and supportive therapy.
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Pregabalin and amitriptyline as monotherapy or as low-dose combination in patients of neuropathic pain: A randomized, controlled trial to evaluate efficacy and safety in an Eastern India teaching hospital p. 437
Sourav Chakrabarty, Samar Biswas, Tamoghna Maiti, Abhijit Das, Ananya Mandal, Prasun Banerjee
DOI:10.4103/aian.AIAN_144_18  
Objectives: The main objective is to compare efficacy and safety of pregabalin and amitriptyline monotherapy with their low-dose combination in patients of neuropathic pain (NeuP). Methodology: In this parallel-group, open-label interventional study at the Neurology Outpatient Department of Bankura Sammilani Medical College, a total of 147 patients were randomly allocated into three groups and were prescribed the following drugs – Group P (n = 42) pregabalin 150 mg once daily, Group A (n = 34), amitriptyline 25 mg once daily, and Group Z (n = 37) = pregabalin (75 mg) + amitriptyline (10 mg) as combination once daily. They were followed up after 4, 8, and 12 weeks. Efficacy was assessed by NeuP symptom inventory score (NPSI) and safety was assessed by treatment-emergent adverse events. Results: Final assessment was done on 92 patients (P = 31, A = 31, Z = 30). Males were predominant (71.7%). NPSI score significantly decreased in every group from baseline (P < 0.0001). There was no difference of NPSI score between groups at any level of follow-up. Percentage of adverse drug reactions were maximum (44.9%) in amitriptyline monotherapy group and lowest in combined group. However, amitriptyline monotherapy was the cheapest treatment option among these three. Conclusion: Combining pregabalin and amitriptyline at low doses proved to be equally effective but more tolerable compared to individual higher dosage monotherapy. However, if tolerability is good, amitriptyline monotherapy can be an attractive choice in economically challenged group of patients.
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Central disorders of hypersomnolence in children and adults: A comparative study from South India p. 442
Madhukar Trivedi, Sapna Erat Sreedharan, Shana N Nair, CA Anees, JP Unnikrishnan, PS Sarma, Ashalatha Radhakrishnan
DOI:10.4103/aian.AIAN_293_18  
Background: Narcolepsy and idiopathic hypersomnolence (IHS) are rare disorders. In Western populations, the reported prevalence of narcolepsy is 0.02%–0.05%. In Indian subcontinent, there are few reports on narcolepsy and none on IHS so far. Here, we compared the clinical and polysomnographic profile of narcolepsy/IHS among the pediatric and adult groups. Materials and Methods: The patients presenting with excessive daytime sleepiness (EDS) attending sleep clinic from January 2010 to December 2015 were included. Patients were diagnosed with narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and IHS based on the International Classification for Sleep Disorders criteria. Patients with secondary causes of EDS were excluded from the study. Results: A total of 56 patients were included in the study (29 males and 27 females). The mean age of symptom onset was 29 years (males – 34 years and females – 24 years). Twelve (21%) patients had NT1, five (9%) patients had NT2, whereas 38 (68%) patients had IHS compared to narcolepsy, the IHS had an older mean age at presentation. The average time from symptom onset to diagnosis was 71 months. Classical tetrad of narcolepsy was rarely found in pediatric cohort, but they had more behavioral problems and weight gain. Pediatric cohort of IHS also reported behavioral problems. The mean sleep-onset latency was 3.1 min, while the mean rapid eye movement latency was 7.2 min. Conclusion: The pediatric narcolepsy patients tend to have less classical symptoms and more behavioral/eating problems as compared to adult cohort. There is significant delay in diagnosing narcolepsy, indicating the need to increase awareness among the physicians about this rare treatable disorder.
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Prevalence of malnutrition in Parkinson's disease and correlation with gastrointestinal symptoms p. 447
Birinder Singh Paul, Tejinder Singh, Gunchan Paul, Dinesh Jain, Gagandeep Singh, Sandeep Kaushal, Rajoo Singh Chhina
DOI:10.4103/aian.AIAN_349_18  
Background: Parkinson's disease (PD) patients are at a higher risk of malnutrition with the overall prevalence estimated to be 3%–60%, but there are limited data in India regarding nutritional assessment of PD. Aim: This study aims to assess nutritional status of PD patients and correlate the disease factors and gastrointestinal tract (GIT) symptoms with nutritional status. Materials and Methods: The PD cohort was assessed for demographic factors, nutritional assessment was done by Mini-Nutritional Assessment (MNA) Scale, and GI symptoms were assessed by validated scales. Age- and gender-matched cohort controls were randomly selected to correlate the GIT symptoms influencing nutritional status. The study population was divided into two groups according to the MNA score; Group I malnourished/at risk of malnutrition (score <23.5) or Group II normal nutrition (>23.5). The two subgroups were then compared. Results: We assessed 75 patients of PD and 35 age- and gender-matched controls. According to anthropometric criteria, 23% of the PD population was underweight, and according to biochemical assessment, 17.3% had hypoalbuminemia along with anemia. According to MNA scale, 12% were malnourished and 45.3% were at risk of malnutrition. Hence, a total of 57.3% patients in Group I (with abnormal nutrition) as compared to 14% of the controls were at risk of malnutrition while none was found to be malnourished. In our study, GIT symptoms, such as sialorrhea and dysphagia was reported by 29.3% each and constipation by 41.3% patients. While comparing GI symptoms within the two MNA groups, there was statistically significant relationship of all GI manifestations, sialorrhea (P = 0.041), dysphagia (P = 0.00081), and constipation (P = 0.0042) with malnutrition. There was no statistical significant difference between groups for age (P = 0.54), gender (P = 0.903), and duration of disease (P = 0.743). Conclusions: The data suggest that about 45% of PD patients are at risk of malnourishment. MNA Score is a validated nutritional assessment tool and anthropometric or biochemical measures alone cannot identify all the malnourished population. PD patients at risk of malnutrition or malnourished do have symptoms of dysphagia, sialorrhea, and constipation as compared to PD patients with normal nutrition.
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Long-term mortality risk of people with epilepsy who underwent seizure monitoring p. 453
Shishir N Duble, VS Nandini, Ashalatha Radhakrishnan, Ramshekhar Menon, Ajith Cherian, P Sankara Sarma, Sanjeev V Thomas
DOI:10.4103/aian.AIAN_134_18  
Aim: The aim is to study survival outcome and sudden unexpected death in epilepsy (SUDEP) of people with epilepsy who underwent epilepsy monitoring. Subjects and Methods: Between 2000 and 2004, 558 persons were admitted to the epilepsy monitoring unit of SCTIMST who fulfilled the selection criteria. Their survival status as on December 31, 2013, was ascertained by clinic attendance record and by mail or telephone contact. Results: Five hundred and fifty-eight persons with epilepsy (males 319, 6408 person-years) were included in this study. There had been 20 deaths till December 31, 2013, and 5 additional deaths were reported when followed up till May 2016. The standardized mortality ratio was 5.35 and higher for males (6.25) than for females (3.52). Those with generalized seizures (tonic and myoclonic seizures), electroencephalography (EEG) showing multifocal and generalized interictal discharges, and polypharmacy had a higher risk of mortality. SUDEP accounted for 5 deaths. Conclusion: People with refractory epilepsy who had undergone presurgical video EEG monitoring had higher mortality risk. Generalized or myoclonic seizures, multifocal or generalized interictal discharges, and polypharmacy independently increased their risk of mortality. SUDEP is an important cause of death.
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Familial Creutzfeldt-Jakob disease in an Indian kindred p. 458
Sarosh M Katrak, Apoorva Pauranik, Shrinivas B Desai, Simon Mead, Jon Beck, Sebastian Brandner, John Collinge
DOI:10.4103/aian.AIAN_214_19  
It is now known that the inherited prion disease is caused by over 60 different mutations in the Prion protein (PRNP) gene. Four missense mutations at codons 102, 178, 200 and 210, account for over 95% of these cases. In this study we describe, a large Indian family with familial Creutzfeldt Jakob Disease (fCJD). One affected member presented with a presenile dementia, a protracted clinical course and characateristic MRI features. Genetic analysis revealed a D178N mutation in the 2 affected individuals and 7 unaffected members. The neuropathological examination of the brain of one of the affected member was conspicuous by spongiform degeneration, neuronal loss and gliosis. This is a detailed report of a genetically and neuropathologically proven fCJD from India.
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EDITORIAL COMMENTARY Top

Familial CJD- A brief commentary p. 462
Satish Chandra, Anita Mahadevan, SK Shankar
DOI:10.4103/aian.AIAN_508_19  
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ORIGINAL ARTICLES Top

Comorbidities and long-term outcomes in a cohort with myasthenic crisis: Experiences from a tertiary care center p. 464
Ajith Sivadasan, Mathew Alexander, Sanjith Aaron, Vivek Mathew, Shalini Nair, Karthik Muthusamy, AT Prabhakar, Rohit N Benjamin, Atif Shaikh, Gideon Rynjah
DOI:10.4103/aian.AIAN_197_19  
Introduction: There is scarce literature regarding the clinical course, comorbidities and long-term outcomes after myasthenic crisis (MC). The natural history of myasthenia gravis (MG) in this subset remains uncertain. Methods: The study included a cohort admitted with MC (2007–2017) in a tertiary care hospital. The comorbidities, outcomes after discharge, and prognostic factors were analyzed. Results: Sixty-two patients (89 episodes of MC) were included. Demographic data was comparable between the early- (<50 years) and late-onset (≥50 years) groups. Comorbidities included stress cardiomyopathy (14.5%), arrhythmias (6.4%), neuropathy (17.7%), pancytopenia (12.9%), encephalopathy (11.2%), neuromyotonia (4.8%), myelopathy (3.2%), and myositis (3.2%). Pulmonary embolism (P < 0.008), dysautonomia (P < 0.002), sepsis (P < 0.008), neuropathy (P < 0.002), and phrenic dysfunction (P < 0.016) were associated with prolonged ventilation. Majority of the patients (42, 67.7%) had a favorable outcome (disease status) as defined by remission/minimal manifestations at the time of last follow-up (median 36 months, IQR 15–66). Persistent bulbar weakness (P < 0.001), neuropsychiatric illness (P < 0.001), and comorbidities (P < 0.017) were associated with refractory MG. Eighteen patients (29%) had recurrent crisis. Eleven patients succumbed in the cohort. The main predictors of mortality were tumor progression (P < 0.001) and cardiac illness (P < 0.004). Discussion: A comprehensive treatment approach in MC will translate to good short- and long-term outcomes. The main cornerstones of therapy will include (1) Identification of refractory MG with the implementation of phenotype-based therapy; (2) Addressing comorbidities including cardiac autonomic neuropathy, bulbar weakness, phrenic dysfunction; and (3) Meticulous tumor surveillance.
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EDITORIAL COMMENTARY Top

Myasthenic crisis – Comorbidities, complications, long-term outcomes: The challenges p. 472
Jagarlapudi M. K. Murthy
DOI:10.4103/aian.AIAN_472_19  
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SHORT COMMUNICATIONS Top

Interleukin 18 polymorphisms and its serum level in patients with multiple sclerosis p. 474
Hamidreza Jahanbani-Ardakani, Fereshteh Alsahebfosoul, Masoud Etemadifar, Seyed-Hossein Abtahi
DOI:10.4103/aian.AIAN_515_18  
Background: Multiple sclerosis (MS) is a chronic demyelinating disorder of central nervous system. Although the definite pathogenesis of MS has not been understood, crucial role of environmental and genetic risk factors has been proposed. Propose: To determine the serum level of interleukin-18 (IL-18) as well as gene polymorphisms of IL-18 (rs1946518, rs360719, and rs187238). Methods: In this case–control study, 110 MS patients diagnosed according to the McDonald criteria and 110 healthy individuals were recruited. IL-18 gene polymorphisms were genotyped by polymerase chain reaction high-resolution melt test, and IL-18 serum level was determined by enzyme-linked immunosorbent assay technique. Results: The mean age of the MS patients (89 females and 21 males) and the control group (89 females and 21 males) was 30.3 ± 9.25 and 30.28 ± 9.13 years, respectively. The mean serum levels of IL-18 in MS patients and healthy individuals were 341.56 ± 39.22 Pg/Ml and 146.52 ± 29.30 Pg/Ml, respectively (P < 0.001). The genotype of rs1946518 (but not rs360719 and rs187238) was significantly different between groups (P = 0.037 and P = 0.069, respectively). Conclusion: In this study, we showed the significant higher IL-18 serum level and significant different frequencies of two polymorphisms of IL-18 in MS patients. These results show the important roles of IL-18 in MS pathogenesis. However, more studies are needed to verify our results in larger sample size.
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Errors in the diagnosis of stroke-tales of common stroke mimics and strokes in hiding p. 477
Sucharita Ray, Kamalesh Chakravarty, Heena Kathuria, Vivek Lal
DOI:10.4103/aian.AIAN_80_19  
Introduction: Stroke mimics are some of the common causes of misdiagnosis of stroke, with an attendant surfeit of finances and resources. Aim: We attempt to discuss some of the common neurological conditions mimicking stroke in the emergency. Methods: We reviewed the articles in English discussing stroke mimics in the last 5 years of publication. Purpose of the Review: We discuss the most common causes of stroke mimics encountered in neurological practice. In this short communication, we shall focus on the discussion of the diagnostic pitfalls and clinical clues that will help distinguish mimics from a true stroke.
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Count of fasciculation in ultrasound can predict the prognosis of amyotrophic lateral sclerosis p. 482
Hiroyuki Todo, Katsuya Nishida, Ryuki Ando, Hiroshi Yamasaki, Naonobu Futamura, Itaru Funakawa
DOI:10.4103/aian.AIAN_429_18  
Background: Although muscle ultrasound (MUS) is known to facilitate the diagnosis and evaluation of the severity of amyotrophic lateral sclerosis (ALS), the number of fasciculation has been scarcely examined as a predictive marker of the prognosis in ALS. Objective: The objective of this study was to examine the predictive value of fasciculation number for the prognosis of ALS. Materials and Methods: We examined fasciculation count (FasC), defined as the number of fasciculation per unit of time and area in MUS, of 11 patients with clinically probable or definite ALS. Thereafter, they were observed for maximally 2 years, unless they reached the endpoint of decease or receiving tracheostomy. Results: Six patients, who thereafter reached the endpoint within 2 years, had significantly higher FasC (223 [49.3] vs. 34 [13], P = 0.0043) and shorter disease duration (7 [2.3] vs. 33 [17], P = 0.0022) at MUS than the remaining five patients without reaching the endpoint. Discussion and Conclusion: Our study suggested that high FasC in MUS can predict rapid progression in ALS. Due to the limitations such as small sample size, suboptimal length of the observational period, and confounding factor of disease duration, further investigations are required.
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Patients with disorders of consciousness in India: Preliminary results from a pilot survey p. 485
Davide Sattin, Nirmal Surya, Caterina Pistarini, Paolo Tonin, Hitav Someshwar, Milena Caputo, Matilde Leonardi
DOI:10.4103/aian.AIAN_355_18  
The epidemiological data of Indian patients with disorders of consciousness (DOC), specifically vegetative state and minimally conscious state, have not been investigated. The present study sought to explore the current state of the art in India for patients with DOC promoting a pilot survey. An ad hoc questionnaire was sent to a total of 400 Indian professionals who are affiliated to various centers; 59 professionals completed the questionnaire and 52 of them declared that their centers hospitalized patients with DOC in the last year for rehabilitation/medical treatments. The majority of the professionals were from Maharashtra region. The main preliminary findings showed that the prevalence rates of traumatic and nontraumatic etiologies were equally distributed, that the rate of use of the coma recovery scale-revised was low, and that the rehospitalization was always or frequently possible in neurological and rehabilitation units. The extrapolated estimated rate of patients with DOC hospitalized in the centers involved in 2017 was equal to 4 per million of population in Maharashtra region. More than 50% of the professionals declared that there were neither sufficient nor adequate services for caregivers' support. Even if the present pilot survey has some limitations, the present article offers the first preliminary data on patients with DOC in Indian country.
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IMAGES IN NEUROLOGY Top

Isolated and asymmetric basal ganglia involvement in early subacute sclerosing panencephalitis p. 488
Mahesh Kamate, Mayank Detroja
DOI:10.4103/aian.AIAN_249_18  
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TEACHING NEUROIMAGE Top

Vertical diplopia: Skew deviation and medullary lesion p. 490
Arunmozhimaran Elavarasi, Balachandran Mani
DOI:10.4103/aian.AIAN_46_19  
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CASE REPORTS Top

Delayed propriospinal myoclonus following dorsal spinal cord surgery p. 491
Vijay Sardana, Sunil Kumar Sharma
DOI:10.4103/aian.AIAN_195_18  
Cerebral disorders are known to be associated with myoclonus, but spinal pathologies have received little attention as a causative factor in movement disorders. Propriospinal myoclonus (PSM) is a rare hyperkinetic movement disorder caused by activity of a spinal pattern generator localized in a few segments of the spinal cord, spreading to other intraspinal segments via propriospinal pathways. Majority of cases of PSM are reported as functional movement disorders. Structural lesions were found in only a small number of reported cases. We present this rare case report of a patient who developed PSM 2 years following spinal surgery, done 5 years ago for D6–D7 vertebral body collapse. To the best of our knowledge, only few cases of PSM have been reported after spinal surgery and none from India.
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A preventable ataxia: Cerebrotendinous xanthomatosis p. 493
Bhagya Shaji, B Srikumar, Dileep Ramachandran
DOI:10.4103/aian.AIAN_126_18  
Cerebrotendinous xanthomatosis is an autosomal recessive inborn error of metabolism that is an often missed but treatable cause of hereditary ataxia. We report a case of cerebrotendinous xanthomatosis (CTX) that was diagnosed only after the development of cognitive decline and adult onset ataxia in a 35-year-old man. He had poor scholastic performance in childhood followed by gradually progressive cognitive decline. He presented to us with severe cerebellar ataxia and oculomotor apraxia. The key features that led to the diagnosis of CTX were the history of cataracts in childhood and Achilles tendon xanthoma. His brain magnetic resonance imaging showed characteristic features of CTX, and the diagnosis was confirmed by demonstrating the mutation in exon 2 of the CYP27A1 gene. The recognition of CTX earlier could have prevented his significant disabilities. The definitive treatment is oral chenodeoxycholic acid, which will prevent the accumulation of the cholestanol, which is thought to be responsible for the neurotoxicity.
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Adult-onset isolated hemichorea revealing iatrogenic hypoparathyroidism and bilateral basal ganglia calcification p. 496
Karan Desai, Priyanka Walzade, Sangeeta Hasmukh Ravat, Pankaj A Agarwal
DOI:10.4103/aian.AIAN_123_18  
Isolated hemichorea (HC) in adults has a relatively restricted differential diagnosis including stroke of contralateral basal ganglia nuclei, nonketotic hyperglycemia, and basal ganglia toxoplasmosis in HIV infection. Hypoparathyroidism-related basal ganglia calcification can potentially cause neurological problems, including movement disorders, that are usually bilateral in keeping with bilateral symmetric lesions. We report a patient with video-documented isolated, adult-onset HC due to iatrogenic hypoparathyroidism and bilateral basal ganglia calcification. A 47-year-old woman presented with isolated adult-onset HC of 2 years' duration as the presenting and only neurological feature of hypoparathyroidism and bilateral extensive basal ganglia calcification, 20 years after thyroidectomy-induced hypoparathyroidism. Significant improvement in the unilateral hyperkinesia was noted after correction of hypocalcemia and hypoparathyroidism at 3 months. Isolated HC in adults is a rare presenting feature of hypoparathyroidism with bilateral basal ganglia calcification and is treatable with correction of the underlying metabolic abnormality. In all cases with a movement disorder and brain calcification, hypoparathyroidism should be actively sought as this treatable condition must not be missed.
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Risperidone-induced tardive akathisia: A rare antipsychotic side effect with management issues p. 499
Biswa Ranjan Mishra, Rajeev Ranjan, Debadatta Mohapatra, Santanu Nath
DOI:10.4103/aian.AIAN_111_18  
Akathisia is a movement disorder, a common extrapyramidal side effect that has been reported to occur primarily with antipsychotics and some neurological conditions. It is manifested by a subjective feeling of inner restlessness along with objective evidence of motoric restlessness. Tardive akathisia (TA) is rare, and there is very sparse literature available as regards to its phenomenology and management. We report a case of TA that occurred after 10 months of starting atypical antipsychotic, risperidone, and challenges faced in management.
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Treatment of catatonia in Parkinson's disease with electroconvulsive therapy p. 501
Vinutha Ramesh, Ashish Sharma, Veenita Sharma, Aditya Somani
DOI:10.4103/aian.AIAN_308_18  
Parkinson's disease (PD) is known to have associated nonmotor manifestations including psychiatric symptoms such as depression and psychosis. Catatonia has been reported extremely rarely in patients of PD. The case described here is a rare example of catatonia in a patient with PD with psychosis. Treatment with electroconvulsive therapy (ECT) brought improvement in symptoms of both PD and catatonia. ECT appears to be an effective treatment option in patients of PD, especially with psychiatric manifestations.
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Phencyclidine: A rare cause of saccadic intrusions p. 503
MN Shameer Nijam, Narmathey Thambirajah, Dhanushka Vithanawasam, Kumarangie Vithanage, Damith S Liyanage, I Kishara Gooneratne, Sunethra Senanayake
DOI:10.4103/aian.AIAN_174_18  
Saccadic intrusions such as opsoclonus and ocular flutter are often due to a paraneoplastic or a parainfectious condition. Toxins/drugs may rarely cause them. Herein, we report a rare case of ocular flutter/opsoclonus due to phencyclidine (PCP) toxicity. Our patient is a 21-year-old male who presented with a 3-day history of headache, generalized ill health, and aggressive behavior. He was admitted with reduced level of consciousness following generalized seizures. He had features of sympathetic overactivity with ocular flutter and opsoclonus. Urine toxicology was positive for PCP. Despite supportive care, he succumbed to complications of rhabdomyolysis. Several drugs including cocaine, phenytoin, lithium, and amitriptyline are known to cause ocular flutter/opsoclonus rarely. It is poorly described with PCP. This case highlights PCP as a rare cause of toxin-induced saccadic intrusions and attempts to postulate its pathogenesis. Moreover, our report is the first case of PCP intoxication in Sri Lanka and one of the few documented reports in the South Asian region. Therefore, it represents a significant worrisome alarm about the spread of this substance in this region.
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CLINICOPATHOLOGICAL CONFERENCE Top

Multiple neurologic deficits and cognitive decline in a young woman p. 506
Arunmozhimaran Elavarasi, Jacob George, Mehar Chand Sharma, Kalpana Kumari, Ajay Garg, Awadh Kishor Pandit, Abhishek Satapathy, Vinay Goyal
DOI:10.4103/aian.AIAN_293_19  
We present the clinicopathologic conference of a 34-year-old lady with history of facial palsy 14 years ago who developed new deficits of mononeuritis multiplex, maculopapular rash, pancytopenia, splenomegaly, lung involvement and cognitive decline rapidly over three years. Investigations revealed pancytopenia, reversal of albumin globulin ratio, mediastinal adenopathy, ANA positivity, low C3 levels with the CSF being inflammatory and MRI showing extensive hemorrhagic lesions with mass effect. She had a rapidly progressive fatal course over three years with the disease being undiagnosed. This case was presented in the annual meeting of the Indian Academy of Neurology in September 2018.
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LETTERS TO THE EDITOR Top

Extensor plantar response: The examination technique makes a crucial difference p. 513
Sarma R. K. Gosala
DOI:10.4103/aian.AIAN_425_18  
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Differential diagnoses of amyotrophic lateral sclerosis are more variegated than anticipated p. 513
Josef Finsterer
DOI:10.4103/aian.AIAN_467_18  
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Infection and epilepsy: Current dilemma p. 514
Deepti Vibha
DOI:10.4103/aian.AIAN_519_18  
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Reversal of anticoagulation effect of dabigatran with idarucizumab, for thrombolysis in acute ischemic stroke: Inimicus inimico amicus p. 515
Boby V Maramattom, Joe Thomas
DOI:10.4103/aian.AIAN_536_18  
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Dengue fever with facial palsy: A rare neurological manifestation p. 517
Vijay Sardana, Rahi Kiran Bhattiprolu
DOI:10.4103/aian.AIAN_462_18  
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Hypokalemic quadriparesis: A rare manifestation of dengue fever p. 519
Veer Bahadur Singh, Harish Kumar
DOI:10.4103/aian.AIAN_512_18  
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Myotonic dystrophy type 1 complicated by colonic obstruction due to a bezoar p. 520
Aaron de Souza, Sanjeev Gupta
DOI:10.4103/aian.AIAN_529_18  
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Identification and in Silico characterization of a novel CASK c.2546T>C (p.V849A) mutation in a male infant with pontocerebellar hypoplasia p. 523
Akella Radha Rama Devi, Lokesh Lingappa, Shaik Mohammad Naushad
DOI:10.4103/aian.AIAN_2_19  
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Expanding the spectrum of polymerase gamma-related ataxia p. 525
Harsh Vardhan Gupta, Kayla Karlowski, Tekalign Burka
DOI:10.4103/aian.AIAN_3_19  
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Nonarteritic anterior ischemic optic neuropathy and stroke in young p. 526
Nataraja Pillai Venugopal, Sherin Kummararaj, Govindaraj Kummararaj
DOI:10.4103/aian.AIAN_407_18  
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Tuberculous encephalitis with aphemia detected only by 18F-fluorodeoxyglucose-positron emission tomography p. 527
Boby Varkey Maramattom, Joe Thomas, Surya Joseph
DOI:10.4103/aian.AIAN_468_18  
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Lacosamide associated complete heart block in elderly p. 529
Indu Ghanshyam Bhana, Mahendra Chourasiya, Soaham Dilip Desai
DOI:10.4103/aian.AIAN_473_18  
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Neuromyelitis optica spectrum disorder with vertical gaze palsy and hypersomnolence p. 530
Jomal Mathew, Madhukar Mohan, Ashok Menon
DOI:10.4103/aian.AIAN_496_18  
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Prevalence of epilepsy and its association with exposure to Toxocara canis: A community-based, case–control study from rural Northern India p. 533
Manish Modi, Rajveer Singh, Manoj Kumar Goyal, Jitender Gairolla, Gagandeep Singh, Vivek Rishi, JS Thakur, RK Sehgal, Vivek Kumar Garg, Niranjan Khandelwal, Parampreet S Kharbanda, S Prabhakar, Vivek Lal
DOI:10.4103/aian.AIAN_32_19  
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Management of benign paroxysmal positional vertigo not attributed to the posterior semicircular canal: A case series p. 533
Petros V Vlastarakos, John Plioutas, Nikolaos S Tsilis, Thomas P Nikolopoulos
DOI:10.4103/aian.AIAN_437_18  
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Partial status epilepticus in cerebral venous sinus thrombosis, initial manifestation of polycythemia vera p. 536
Sinan Eliaçik, Ömer Önder Savas, Erdal Komut, Funda Uysal Tan
DOI:10.4103/aian.AIAN_532_18  
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Secondary narcolepsy masquerading as obstructive sleep apnea p. 537
Sachin Sureshbabu, Ajay Asranna, Sudhir Peter, Sobhana Chindripu, Gaurav K Mittal
DOI:10.4103/aian.AIAN_19_19  
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Juvenile onset niemann-pick type C disease with refractory seizures p. 539
Banshi Lal Kumawat, Pankaj Kumar Saini, Chandra Mohan Sharma, Manisha Sharma, LS Manu
DOI:10.4103/aian.AIAN_292_19  
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Subacute myelopathy: Think beyond neuromyelitis optica spectrum disorder p. 541
Ananthanarayanan Kasinathan, Renu Suthar, Sameer Vyas, Arushi Gahlot Saini, Naveen Sankhyan, Savita Attri
DOI:10.4103/aian.AIAN_4_19  
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Short-course self-medication of metronidazole leading to acute toxic encephalopathy and ataxia p. 543
Yatin Sagvekar, Virti Shah, Anshu Rohatgi, Neha Pandita, Rahul Sharma, Rajeswari Rajan, Dhrumil Shah
DOI:10.4103/aian.AIAN_43_19  
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