Neurology

No evidence of disease activity (NEDA) in multiple sclerosis - Shifting the goal posts Lekha Pandit Annals of Indian Academy of Neurology 2019 22(3):261-263 A combined endpoint measure to define no evidence of disease activity (NEDA) is becoming increasingly appealing in the treatment of multiple sclerosis (MS). Initial efforts using a 3 parameter NEDA monitored disease activity using clinical and MRI lesion data. Later refinements, introduced more recently, include brain atrophy measurement and cognitive function analysis in defining NEDA-4. Using these stringent criteria clearly differentiated the usefulness of different disease modifying agents (DMDs) in achieving and sustaining NEDA over time. This in turn has changed attitudes and strategies in management of MS.

The neurologist and artificial intelligence: Titans at crossroads Venugopalan Y Vishnu, Pulikottil Wilson Vinny Annals of Indian Academy of Neurology 2019 22(3):264-266 Clinical judgment to reach final diagnosis has remained a challenge since time immemorial. The present times are witness to artificial intelligence (AI) and machine learning programs competing to outperform the seasoned physician in arriving at a differential diagnosis. We discuss here the possible roles of AI in neurology.

The Ape's Tail Ajith Cherian Annals of Indian Academy of Neurology 2019 22(3):266-266

Neurodegeneration with brain iron accumulation Amit Batla, Chandana Gaddipati Annals of Indian Academy of Neurology 2019 22(3):267-276 The term NBIA encompasses a heterogeneous group of inherited disorders characterized clinically by progressive extra pyramidal syndrome and pathologically by excessive iron deposition in brain, primarily affecting the basal ganglia (globus pallidus mainly).The hallmark of this syndrome is the age specific phenotypic presentation and intraphenotypic heterogeneity. NBIAs at present include ten subtypes with genes identified in nine subtypes. They form an important differential diagnosis for the phenotype of global developmental delay in infancy/childhood to dystonia-parkinsonism or isolated parkinsonism at all ages and also for the isolated craniocervical dystonia of adult onset. There needs to be a high index of clinical suspicion for this syndrome and the evaluation includes MRI brain T2* weighted imaging which reveal symmetrical iron deposition in bilateral globus pallidi and other basal ganglia. The T2 * imaging pattern of iron deposition varies amongst the different subtypes and the combination of clinical phenotype and MRI signature makes it easier to confidently make a diagnosis of NBIA and to recommend genetic testing. The treatment to date is mostly symptomatic with targeted therapies on the horizon.

Association of serum levels of calcitonin gene-related peptide and cytokines during migraine attacks Dawei Han Annals of Indian Academy of Neurology 2019 22(3):277-281 Background: During a migraine attack, trigeminal activation results in the release of calcitonin gene-related peptide (CGRP), which stimulates the release of inflammatory cytokines playing an important role in migraine. Objective: We analyze the relation between CGRP and cytokines during attacks to explore the possible mechanism of migraine. Materials and Methods: Migraine patients and healthy control were recruited at the Department of Neurology, the Sixth People's Hospital of Fuyang City, between March 2018 and July 2018. The protein levels of interleukin (IL)-1β, IL-2, IL-6, IL-10, tumor necrosis factor-alpha (TNF-α), and CGRP were determined from the sera of patients with migraine and control subjects by enzyme-linked immunosorbent assay kits. Spearman's rank correlation coefficient was also determined to calculate the correlation between CGRP and inflammatory factors levels. Results: The level of IL-1β, IL-6, TNF-α, and CGRP in migraine group were significantly higher than normal group (P < 0.05). The level of CGRP was significantly correlated with IL-1 β (r = 0.30, P < 0.05) and IL-6 (r = 0.94, P < 0.05), but not significantly correlated with IL-2 (r =−0.047, P = 0.75), IL-10 (r = 0.12, P = 0.43), and TNF-α (r = 0.05, P = 0.72). Conclusions: In our study, we found migraine patients had a higher IL-6, IL-1β, and TNF level than healthy controls and the level of CGRP was related significantly with the level of IL-1β and IL-6. In conclusion, our results suggest that IL-1β and IL-6 may be involved in the pathogenesis of migraine attacks and CGRP related with the secretion of cytokines.

Cranial Autonomic symptoms, neck pain: Challenges in pediatric migraine Zeliha Haytoglu, Mihriban Ozlem Herguner Annals of Indian Academy of Neurology 2019 22(3):282-285 Objectives: More than just a headache, migraine attack is a severe, prolonged head pain preceded and/or followed by a constellation of symptoms. Getting a proper diagnosis will be the most challenging step of migraine care. When cranial autonomic symptoms (CASs), and/or neck pain are observed, children are often exposed to advanced tests for additional diseases. The aim of this study was to investigate the frequency of these symptoms in migraine and to compare the clinical characteristics of patients with and without these symptoms. Frequency of the patients that exposed to the additional investigations was searched. Materials and Methods: In this prospective study between February 2016 and March 2017, 170 pediatric patients who were referred to our tertiary teaching hospital with migraine were enrolled. Results: A total of 170 children, 61 male (35.9%) and 109 female (64.1%) were included in the study. CASs were present in 68 patients (40%), single symptom in 31 (45.6%), and multiple symptoms in 37 (54.4%) patients. Of 68 patients with CAS, 24 (35%) patients were referred to allergists and all were tested for inhaler specific IgE and skin tests. Seventy (32.9%) patients had neck pain/stiffness in which 28 (40%) were exposed to radiation. CAS and neck pain were more frequent in patients with frequent attacks (P = 0.04 and P = 0.032, respectively). Neck pain was more frequent in patients with CAS (P = 0.029). Conclusions: It is important for pediatricians and primary care physicians to be aware of the common nature of CASs and neck pain/stiffness in children with migraine to prevent unnecessary procedures. High frequency of migrain attacks was associated with high frequency of CAS and neck pain.

Memantine ameliorates migraine headache Sundar Shanmugam, Kranthi Karunaikadal, Sathyanarayanan Varadarajan, Muthuraj Krishnan Annals of Indian Academy of Neurology 2019 22(3):286-290 Background and Objective: A significant number of migraine patients do not find effective and safe treatment to reduce the frequency and severity of their migraine attacks. Hence, a need for newer therapeutic agent exists. In this study, we examined the efficacy and safety of memantine for the treatment of migraine. Materials and Methods: It was a randomized, placebo-controlled, double-blind study including adult patients with 3–12 migraine headache for the last 6 months conducted in India. Patients received memantine (10 mg/day, once a day) or placebo for the period of 24 weeks after a washout period. Migraine frequency per month, the 50% responder rate, rescue medication use, and adverse events were recorded every 4 weeks. Results: Among 81 patients screened, 60 were enrolled for the study. Thirty patients received memantine and other 30 received placebo. Data were analyzed for 28 patients in memantine group and 29 patients in placebo group. At the baseline, all the parameters were similar in both groups. By 24 weeks, migraine frequency/4 weeks was memantine group versus placebo; 2.57 (±0.38) versus 5.07 (±0.69), P = 0.003 and rescue medication use was 0.75 (±0.23) versus 3.72 (±0.63) P = 0.0001. The 50% responder rate was 85.7% versus 51.7% (P = 0.005). Only a few mild adverse events were recorded in both the groups. No severe adverse events and death were recorded during the study. Conclusion: Memantine (10 mg oral, once daily) is effective, well tolerated, and safe for patients with migraine.

Prevalence and predictors of female sexual dysfunction in migraine R Pradeep, Harsha Sundarmurthy, Vivek Karan, Praveen Kulkarni Annals of Indian Academy of Neurology 2019 22(3):291-294 Background: Migraine is a common cause of primary headache, with women being affected thrice as common as men. Very few studies are available on sexual dysfunction in female migraineurs. There are no published studies done on the same in India till now. This study was done to look for the prevalence and predictors of sexual dysfunction disorder in females suffering from migraine. Materials and Methods: This is a cross-sectional study done to look for the prevalence and predictors of female sexual dysfunction in migraine. Sixty female patients with migraine were studied. The International Headache Society's International Classification of Headache Disorders, 3rd Edition, was followed to diagnose migraine with or without aura. Migraine disability assessment scale was used to assess migraine-related disability, and Female Sexual Function Index (FSFI) score was used to assess female sexual function. Results: Sexual dysfunction was found in 78.3% migraineurs. The mean FSFI score was 23.1 ± 4.76. The FSFI scores in all the domains were lower in the individuals studied. Acute headaches resulted in loss of sexual desire among all the migraineurs. Conclusion: Sexual dysfunction is common in migraine with all domains of sexual function being affected. There is a significant negative correlation of sexual function with duration of acute episodes of headache and increasing frequency of migraine attacks per month.

Clinical profile, prognostic indicators, and therapeutic outcomes of pediatric opsoclonus-myoclonus-ataxia syndrome: A single-center experience from South India Karthik Muthusamy, Maya Thomas, Sangeetha Yoganathan, Sniya Valsa Sudhakar Annals of Indian Academy of Neurology 2019 22(3):295-301 Background: Opsoclonus myoclonus syndrome (OMS) is a neuroinflammatory disorder. Indian literature on its clinical profile and outcome is sparse. Objectives: The objective of this study is to describe the clinical profile and analyze outcomes and prognostic predictors in a cohort of children with OMS. Materials and Methods: This was a retrospective study of children with OMS between 2007 and 2017. Results: Twenty-two children were included in the study. The mean age at onset of symptom was 20.9 months (standard deviation [SD]: 7.5). The mean duration of delay in diagnosis was 8.4 months (SD 1.26) with acute cerebellitis being the most common misdiagnosis. Eleven children (50%) were diagnosed with tumor during evaluation and follow-up and 11 children (50%) belonged to idiopathic/postinfectious group. Magnetic resonance imaging brain was normal in all children except for one revealing cerebellar atrophy on follow-up. One child in the paraneoplastic group (neuroblastoma) had a positive PNMA2/Ta onconeural antibody. Children in the tumor group had an earlier age of onset (mean 15.5 vs. 26.3 months), shorter time to onset of opsoclonus from initial symptom (2.54 vs. 7.27 weeks), and higher severity score at presentation (13.7 vs. 11.3) compared to the nontumor group. Children in the nontumor group attained their first remission with treatment earlier (10.9 weeks, SD: 4.5) than the children with tumor (18.72 weeks, SD: 5.8). There was no significant difference in the outcome between the groups. Children with multiple relapses (>3) and late surgical intervention for tumor (>6 months after symptom onset) had a poor outcome. Discussion: A high index of suspicion coupled with early diagnosis and periodic tumor surveillance (even in the initially negative cases) along with aggressive combined multimechanistic immunotherapies is the key in improving outcomes. Conclusion: A high index of suspicion in appropriate clinical circumstances and early aggressive immunomodulation might lead to a better outcome.

Increasing number of therapy sessions of repetitive transcranial magnetic stimulation improves motor development by reducing muscle spasticity in cerebral palsy children Bablu Lal Rajak, Meena Gupta, Dinesh Bhatia, Arun Mukherjee Annals of Indian Academy of Neurology 2019 22(3):302-307 Background: Repetitive TMS (rTMS), a non-invasive neuro-stimulation tool based on the principle of electromagnetic induction is recently being employed both for investigational and interventional purposes. The stimulating effect of rTMS on motor cortex areas of the brain leads to increased motor activity and decreased muscle tone in spastic cerebral palsy (CP) patients. Objective: This modulatory effect of rTMS is used in this study to evaluate its effect on motor function and spasticity by increasing the number of therapy session and keeping frequency of 10Hz and pulse train of 2500 constant. Methods: Total thirty spastic CP patients participated in this study after written informed consent from their parents/guardians. The participants were equally divided into three groups, namely, S-20, S-30 and S-40 depending on the number of therapy sessions. The mean age±SD of participants in different groups were 8.9±3.6, 9.5±2.9 and 8.4±3.5 in S-20, S-30 and S-40 respectively. Participants in S-20, S-30 and S-40 were provided 20, 30 and 40 sessions of rTMS therapy respectively followed by physical therapy of 30 minutes daily. Each rTMS session was of 25 minutes duration and was administered once daily for 5 days a week. Prior to start and after completion of the therapy, pre and post assessment of gross motor function measure (GMFM) for motor function and modified Ashworth scale (MAS) for muscle spasticity was performed on all the participants. Outcomes: The result of pre-versus-post GMFM score showed that 4.27%, 3.12% and 2.36% motor gain was obtained after 40, 30 and 20 sessions of therapy respectively. In addition, significant reduction in spasticity in both upper and limb muscles was also observed in all the three groups.

Alexandros Sfakianakis
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