Seronegative autoimmune encephalitis – A diagnostic and therapeutic dilemma M Netravathi Annals of Indian Academy of Neurology 2019 22(4):369-370

Plasmapheresis for NMOSD: Not a rescue therapy anymore!? Rohit Bhatia, Radhakrishna Pedapati, Siddharth Chopra Annals of Indian Academy of Neurology 2019 22(4):371-372

Critical appraisal of guidelines for evaluation and certification of specified neurological disabilities Inder Puri, Govind Singh, Rajendra Kumar Acharya, Divya Goswami Annals of Indian Academy of Neurology 2019 22(4):373-376 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.

Diagnostic utility of human leukocyte antigen B*15:02 screening in severe carbamazepine hypersensitivity syndrome Youssef Moutaouakkil, Badr Adouani, Yahia Cherrah, Jamal Lamsaouri, Yassir Bousliman Annals of Indian Academy of Neurology 2019 22(4):377-383 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.

William osler and harvey williams cushing: Friendship around neurosurgery Marleide da Mota Gomes Annals of Indian Academy of Neurology 2019 22(4):384-388 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.

Plasma exchange as a first line therapy in acute attacks of neuromyelitis optica spectrum disorders BL Kumawat, Reenu Choudhary, CM Sharma, Deepak Jain, Ashwini Hiremath Annals of Indian Academy of Neurology 2019 22(4):389-394 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.

Epidemiologic features, risk factors, and outcomes of respiratory infection in patients with acute stroke Lunlin Mao, Xiaobo Liu, Peng Zheng, Saiping Wu Annals of Indian Academy of Neurology 2019 22(4):395-400 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.

Antibody negative autoimmune encephalitis- Does it differ from definite one? Sunil Pradhan, Animesh Das, Ananya Das, Madhura Mulmuley Annals of Indian Academy of Neurology 2019 22(4):401-408 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.

Is dementia in Parkinson' disease related to chronic stress, anxiety, and depression? Anita Pal, Nishi Pegwal, Madhuri Behari, Ratna Sharma Annals of Indian Academy of Neurology 2019 22(4):409-413 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.

Lateralized periodic discharges are predictive of seizures in patients with intracerebral hemorrhage Sushma Yerram, Nakul Katyal, Aarti Sarwal, Pravin George, Christopher R Newey Annals of Indian Academy of Neurology 2019 22(4):414-418 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.