Annals of Indian Academy of Neurology
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April-June 2017
Volume 20 | Issue 2
Page Nos. 87-172

Online since Monday, May 8, 2017

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REVIEW ARTICLE  

Limb-girdle muscular dystrophies in India: A review Highly accessed article p. 87
Satish V Khadilkar, Hinaben Dayalal Faldu, Sarika Bapuso Patil, Rakesh Singh
DOI:10.4103/aian.AIAN_81_17  
Limb-girdle muscular dystrophies (LGMDs) are common in India. Information on LGMDs has been gradually evolving in the recent years. This information is scattered in case series and case studies. The aim of this study is to collate available Indian information on LGMDs and put it in perspective. PubMed search using keywords such as limb-girdle muscular dystrophies in India, sarcoglycanopathies, dysferlinopathy, calpainopathy, and GNE myopathy was carried out. The published information on LGMDs in Indian context suggests that dysferlinopathy, calpainopathy, sarcoglycanopathies, and other myopathies such as GNE myopathy are frequently seen in India. Besides these, anecdotal reports of many other forms are available, some with genetic support and others showing immunocytochemical defects. The genotypic information on LGMDs is gradually evolving and founder mutations have been detected in selected populations. Further multicenter studies are necessary to document the incidence and prevalence of these common conditions in India.
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REVIEW: PROGRESS IN MEDICINE (UPDATE ON ADVANCES IN PATHOPHYSIOLOGY) Top

Molecular genetics of epilepsy: A clinician's perspective p. 96
Vikas Dhiman
DOI:10.4103/aian.AIAN_447_16  
Epilepsy is a common neurological problem, and there is a genetic basis in almost 50% of people with epilepsy. The diagnosis of genetic epilepsies makes the patient assured of the reasons of his/her seizures and avoids unnecessary, expensive, and invasive investigations. Last decade has shown tremendous growth in gene sequencing technologies, which have made genetic tests available at the bedside. Whole exome sequencing is now being routinely used in the clinical setting for making a genetic diagnosis. Genetic testing not only makes the diagnosis but also has an effect on the management of the patients, for example, the role of sodium channels blockers in SCN1A+ Dravet syndrome patients and usefulness of ketogenic diet therapy in SLC2A1+ generalized epilepsy patients. Many clinicians in our country have no or limited knowledge about the molecular genetics of epilepsies, types of genetic tests available, how to access them and how to interpret the results. The purpose of this review is to give an overview in this direction and encourage the clinicians to start considering genetic testing as an important investigation along with electroencephalogram and magnetic resonance imaging for better understanding and management of epilepsy in their patients.
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HISTORY OF MEDICINE Top

Frederic Andrews Gibbs and the assassination of John Fitzgerald Kennedy p. 103
Kalyan B Bhattacharyya
DOI:10.4103/aian.AIAN_439_16  
Frederic Gibbs, the peerless expert on electroencephalogrphy was summoned to provide opinion on the EEG tracing of Jack Ruby, who murdered Lee Harvey Oswald, the assassin of John Fitzgerald Kennedy, the American President, in 1963. Gibbs pleaded that the tracing suggested features indicative of psychomotor epilepsy and Ruby killed Oswald in a state of fugue. His view was not agreed upon but Gibbs stood his ground unflinchingly. Subsequent appeals to the higher court spared Ruby from imminent execution and finally he died a natural death from metastatic complications of carcinoma of the lung in 1967.
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ORIGINAL ARTICLES Top

Neurological outcomes following suicidal hanging: A prospective study of 101 patients p. 106
Mohammed Turab Jawaid, S Deepak Amalnath, D. K. S. Subrahmanyam
DOI:10.4103/0972-2327.205773  
Context: Survivors of suicidal hanging can have variable neurological outcomes – from complete recovery to irreversible brain damage. Literature on the neurological outcomes in these patients is confined to retrospective studies and case series. Hence, this prospective study was carried out. Aims: The aim is to study the neurological outcomes in suicidal hanging. Settings and Design: This was a prospective observational study carried out from July 2014 to July 2016. Subjects and Methods: Consecutive patients admitted to the emergency and medicine wards were included in the study. Details of the clinical and radiological findings, course in hospital and at 1 month postdischarge were analyzed. Statistical Analysis Used: Statistical analysis was performed using IBM SPSS advanced statistics 20.0 (SPSS Inc., Chicago, USA). Univariate analysis was performed using Chi-square test for significance and Odd's ratio was calculated. Results: Of the 101 patients, 6 died and 4 had residual neuro deficits. Cervical spine injury was seen in 3 patients. Interestingly, 39 patients could not remember the act of hanging (retrograde amnesia). Hypotension, pulmonary edema, Glasgow coma scale (GCS) score <8 at admission, need for mechanical ventilation, and cerebral edema on plain computed tomography were more in those with amnesia as compared to those with normal memory and these findings were statistically significant. Conclusions: Majority of patients recovered without any sequelae. Routine imaging of cervical spine may not be warranted in all patients, even in those with poor GCS. Retrograde amnesia might be more common than previously believed and further studies are needed to analyze this peculiar feature.
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Unknown patients and neurology casualty services in an Indian metropolitan city: A decades experience p. 109
Achary Umesh, Guru S Gowda, Channaveerachari Naveen Kumar, Dwarakanath Srinivas, Bharath Rose Dawn, Ragasudha Botta, Ravi Yadav, Suresh Bada Math
DOI:10.4103/0972-2327.205764  
Objectives: A large number of unknown patients without any personal, family, or other identification details represent a unique problem in the neurological emergency services of developing countries like India in a context of legal, humanitarian, and treatment issues. These patients pose a diagnostic and management challenge to treating physicians and staff. There are sparse data on these patients. The objective of this study was to know the clinical, socio-demographic, and investigational profile of “unknown” patients. Materials and Methods: We did retrospective chart review of all “Unknown” patients from January 2002 to December 2011, who was admitted under Neurology Emergency Service at a Tertiary Care Neuropsychiatry Center in South Indian Metropolitan City. Clinical and sociodemographic characteristics and clinical outcome of the sample were analyzed. Results: A total of 151 unknown patients were admitted during the 10 years. Out of these, 134 (88.7%) were males with the mean age of 43.8 ± 14.8 years and 95 (63%) were aged >40 years. Among them, 147 (97.4%) were from the urban vicinity, 126 (83.6%) were brought by police and 75 (49.7%) were registered as medico-legal cases. Out of these, only 3 (2%) patients had normal sensorium, whereas 101 (66.9%) presented with loss of consciousness. Forty-one (27.2%) unknown patients had a seizure disorder, 37 (24.5%) had metabolic encephalopathy, 26 (17.2%) had a stroke, 9 (6%) had neuro-infection, and 17 (11.3%) had a head injury. Deranged liver functions were seen in 65 (43%), renal derangement in 37 (24.5%), dyselectrolytemia in 42 (27.8%), and abnormal brain imaging finding in 95 (62.9%) patients. Furthermore, there were 14 (9.3%) deaths. Conclusions: Our findings demonstrate seizures, metabolic causes, and neuro-infections were the primary reasons for admission of unknown patients to neuro-emergency service. This novel Indian study data show the common causes of admission of unknown patients in neurology. This pattern can be useful to guide the approach of healthcare providers in India.
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Study of refractory status epilepticus from a tertiary care center p. 116
Sahil Kohli, Suresh Babu Pasangulapati, Sangeetha Yoganathan, Gideon Lyngsyun Rynjah, AT Prabhakar, Sanjith Aaron, Mathew Alexander, Vivek Mathew
DOI:10.4103/aian.AIAN_385_16  
Objectives: To determine the proportion of refractory status epilepticus (RSE) and super-RSE (SRSE) among patients with status epilepticus (SE) and to analyze RSE and non-RSE (NRSE) in terms of etiology and predictors for RSE. Materials and Methods: Patients were identified from discharge summaries database with keywords of SE and records of the portable electroencephalogram (EEG) machine from January 2011 to March 2016. Results: Two hundred and eighteen events were included in the study with 114 (52.3%) males, bimodal age preponderance age <5 years 30%, and second peak in age 15–65 years 52.8%, preexisting seizures were present in 34.4% (n = 75). Nearly 77.1% had NRSE (n = 168) and 22.9% had RSE (n = 50). This included 17 patients with SRSE (n = 17, 7.8% of all SE). Central nervous system (CNS) infection was a single largest etiological group in SE (69/218, 31.7%). In RSE, autoimmune encephalitis (17/50) and CNS infection (13/50) were the largest groups. De novo seizures (P = 0.007), low sensorium at admission (P = 0.001), low albumin at admission (P = 0.002), and first EEG being abnormal (P = 0.001) were risk factors on bivariate analysis. An unfavorable status epilepticus severity score (STESS) was predictive for RSE (P = 0.001). On multivariate analysis, de novo seizures (P = 0.009) and abnormal EEG at admission (P = 0.03) were predictive for RSE. Conclusions: Fifty patients had RSE (22.9%), of which 17 went on to become SRSE (7.8%). Unfavorable STESS score was predictive for RSE on bivariate analysis. On multivariate analysis, de novo seizures and abnormal initial EEG were predictors of RSE.
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Maintenance of normoglycemia may improve outcome in acute ischemic stroke p. 122
Sruthi S Nair, PN Sylaja, Sapna Erat Sreedharan, Sankara Sarma
DOI:10.4103/0972-2327.194301  
Introduction: Several studies have shown that high admission glucose is associated with poor outcomes after stroke, but the impact of maintenance of normoglycemia on functional outcome during hospitalization for acute ischemic stroke is less well established. Aims: The aim of this study was to examine the independent association of postadmission glycemic status in the 1st week with 3-month functional outcome in patients with acute ischemic stroke. Methods: Patients with acute ischemic stroke admitted within 48 h of symptom onset with National Institutes of Health Stroke Scale (NIHSS) of ≥4 were selected from a prospectively maintained database by chart review. Demographic data, risk factors, NIHSS, and blood glucose values in the 1st week were collected. The primary outcome was Modified Rankin Scale (mRS) score at 3 months (good outcome-mRS ≤2). Results: Over 3 years, 342 patients were enrolled with 220 (64.32%) males. Mean age was 60.5 ± 13.4 years, and median admission score on NIHSS was 10 (interquartile range: 6–16). Blood glucose values persistently <140 mg/dl in the 1st week were associated with a good 3-month functional outcome in univariate analysis (P = 0.036). Hypoglycemic episodes occurred only in 11 (3.22%) patients. Conclusions: Blood glucose values persistently below 140 mg/dl in the 1st week after acute ischemic stroke were associated with a favorable outcome in our study. Future clinical trials are needed to confirm these findings.
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Dorsal sural sensory nerve action potential: A study for reference values p. 127
Sweta Chetan Chaudhari, Khushnuma Anil Mansukhani, Alika Sharma, Lajita Balakrishnan, Aarthika Sreenivasan
DOI:10.4103/0972-2327.194313  
Background: Dorsal sural sensory nerve action potential (SNAP) could help diagnose early or subclinical peripheral neuropathy. Objectives: To establish reference data for dorsal sural SNAP amplitude, latency, and velocity in healthy participants. Materials and Methods: A prospective study was conducted in 45 nerves from healthy participants between 18 and 90 years and stratified into three age groups (a = 18–40 years, b = 41–60 years, and c≥60 years). StataCorp 12.2 statistical program was used for all statistical analyses. Mean-2 standard deviation was used to generate reference values for the lower limit of amplitude and velocity in each age group. ANOVA with Bonferroni correction was used for intergroup comparisons of amplitude and velocity. Regression analysis was used to compute an equation for the predicted amplitude with age, height, and weight as the covariates. Results: The lower limit for amplitude (uv) in Groups a, b, and c was 2.57, 1.97, and 1.01, respectively. The lower limit for velocity (m/s) was 33.6, 32, and 22.8, respectively. Statistical significance was noted between the amplitudes of participants in Groups b and c (P = 0.039) and a and c (P = 0.001). Similarly, velocity was significantly different between Groups b and c (P = 0.04) and a and c (P = 0.008). Age was the covariate with maximum effect on the dorsal sural amplitude. Gender and side-to-side comparison did not show statistical significance for amplitude and velocity measurements. Linear regression analysis of the transformed amplitude gave the predictive equation as (y) =3.338 + age (−0.0167) + height in meters (−0.209) + weight (0.001). Conclusion: This study provides reference data for dorsal sural SNAP in Indian population stratified by age.
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Teratogenic effects of carbamazepine in mice p. 132
Manna Jose, Harikrishnan Vijayakumar Sreelatha, Manjula Valiyamattathil James, Sabareeswaran Arumughan, Sanjeev Varghese Thomas
DOI:10.4103/aian.AIAN_492_16  
Objectives: The aim of this study was to determine the teratogenic effects of carbamazepine (CBZ) in BALB/c mice. Materials and Methods: Mature female and male BALB/c mice (25–30 g) were used for all experiments. After standardization of administration and dose of CBZ, animals in the CBZ-treated groups (CBZ 450 mg/kg and 600 mg/kg) were fed on medicinal diet. The dams in the control group were mated on the same day as that of the CBZ-treated dams. After cesarean section (CS), fetal viability status and weights were recorded. Gross histopathological examination of fetuses was conducted to identify alterations in morphology and external or internal organs due to in utero exposure of CBZ. Results: Out of the nine female animals (three treated on CBZ 450 mg/kg, three treated on CBZ 600 mg/kg and three controls), seven were pregnant, and two (one each from the two CBZ-treated groups) were nonpregnant. All fetuses of the control group (n = 31) and CBZ 450 mg/kg treated group (n = 24) were live, but eight out of the twenty fetuses (40%) of CBZ 600 mg/kg treated group were dead at CS. The birth weight of the fetuses antenatally exposed to CBZ was drastically reduced (0.71 ± 0.06) when compared to control fetuses (1.67 ± 0.12) (P < 0.0001). All the fetuses of the CBZ-treated groups showed stunted physical development. Conclusion: Although oral administration of CBZ to mice is a convenient model to study the effect of CBZ to pregnancy, higher oral dose was associated with increased fetal loss. Some of the fetuses exposed to CBZ demonstrated structural abnormalities and low body weight.
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Clinical and imaging study of isolated and mixed rest and action tremor-essential tremor versus Parkinson's disease p. 138
Sandro Zambito Marsala, Michele Pistacchi, Manuela Gioulis, Franco Ferracci, Livio Capus
DOI:10.4103/aian.AIAN_497_16  
Background: Some patients present an unusual association of both action tremor (AT) and rest tremor (RT) making the differential diagnosis between essential tremor (ET) and Parkinson's disease (PD) difficult. Aim: To investigate this particular clinical picture trying to focus on possible peculiar clinical inferences. Patients and Methods: Twenty-three patients with atypical tremor syndrome were selected for the study. They underwent neurological examination, neuroimaging study, and brain DaTSCAN single-photon emission computed tomography. Results: Twenty-three patients were evaluated; 17 presented mixed-tremor syndrome, while six patients showed only isolated AT or RT. DaTSCAN was pathological in 19 patients and normal in 3 patients. The emerging statistical data highlighted a positive correlation between disease duration and DaTSCAN abnormalities; Fisher's exact test showed a marked difference in evolution toward a dysfunction of dopaminergic pathways in patients with both AT and RT phenotype. Conclusion: The possible correlation between PD and ET has often been discussed without any clear findings. Are these patients suffering from ET prone to develop PD? Or are they the expression of a specific clinical phenotype? Our clinical survey has not led to absolute considerations; however, it seeks to highlight the clinical markers that might arouse the suspicion of extrapyramidal disease in patients with atypical tremor syndrome.
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Predictors of outcome in children with status epilepticus during resuscitation in pediatric emergency department: A retrospective observational study p. 142
Indumathy Santhanam, Sangeetha Yoganathan, V Akila Sivakumar, Rubini Ramakrishnamurugan, Sharada Sathish, Murali Thandavarayan
DOI:10.4103/aian.AIAN_369_16  
Objectives: To study the clinical profile and predictors of outcome in children with status epilepticus (SE) during resuscitation in pediatric emergency department. Materials and Methods: This retrospective study was carried out in a tertiary care teaching hospital. Admission and resuscitation data of children, aged between 1 month and 12 years, treated for SE, between September 2013 and August 2014, were extracted using a standard data collection form. Our SE management protocol had employed a modified pediatric assessment triangle to recognize and treat acute respiratory failure, cardiovascular dysfunction (CD), and subtle SE until all parameters resolved. Continuous positive airway pressure, fluid boluses based on shock etiology, inotropes, and cardiac safe anticonvulsants were the other modifications. Risk factors predicting mortality during resuscitation were analyzed using univariate and penalized logistic regression. Results: Among 610 who were enrolled, 582 (95.4%) survived and 28 (4.6%) succumbed. Grunt odds ratio (OR): 3.747 (95% confidence interval [CI]: 1.035−13.560), retractions OR: 2.429 (95% CI: 1.036−5.698), rales OR: 10.145 (95% CI: 4.027−25.560), prolonged capillary refill time OR: 3.352 (95% CI: 1.339−8.388), and shock requiring >60 mL/kg fluids OR: 2.439 (95% CI 1.040−5.721) were associated with 2−3 times rise in mortality. Inappropriate prehospital treatment and CD were the significant predictors of mortality OR: 7.82 (95% CI 2.10−29.06) and 738.71 (95% CI: 97.11−999), respectively. Resolution of CD was associated with improved survival OR: 0.02 (95% CI: 0.003−0.17). Conclusion: Appropriate prehospital management and treatment protocol targeting resolution of CD during resuscitation could reduce mortality in children with SE.
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Varicella zoster virus infection of the central nervous system – 10 year experience from a tertiary hospital in South India p. 149
Ronald Albert Benton Carey, Vignesh Kumar Chandiraseharan, Anitha Jasper, Tunny Sebastian, Chrusolitha Gujjarlamudi, Sowmya Sathyendra, Anand Zachariah, Asha Mary Abraham, Thambu David Sudarsanam
DOI:10.4103/aian.AIAN_484_16  
Introduction: Varicella zoster virus is an exclusively human neurotrophic virus. The primary infection with the virus causes varicella. The virus remains latent in nervous tissue and upon secondary activation causes a variety of syndromes involving the central nervous system (CNS) including meningoencephalitis and cerebellitis. Materials and Methods: In this study, we looked at the epidemiology, clinical and laboratory features, and outcomes of patients who were admitted with varicella zoster of the CNS from 2005 to 2014. Results: There were 17 patients. Fever was present in 13 patients, seizures in 9 patients and headache and vomiting in 4 patients each. A generalized varicella rash was present in 8 out of 17 patients. A single dermatomal herpes zoster was present in seven patients. Two patients had no rash. Varicella zoster polymerase chain reaction (PCR) in cerebrospinal fluid (CSF) was done in 5 patients of which 4 were positive and 1 was negative. Nine patients had diabetes with an average glycated hemoglobin of 8.6%. Total number of deaths was five. Conclusions: Patients with diabetes who develop varicella or herpes zoster may be at risk for CNS complications. The diagnosis of varicella encephalitis has to rest on a combination of clinical findings and CSF PCR, as neither the rash nor the PCR is sensitive enough to diagnose all the cases with varicella encephalitis.
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SHORT COMMUNICATION Top

Translation and adaptation of stroke aphasia depression questionnaire-10 to Hindi p. 153
Harsimarpreet Kaur, Sakshi Chopra, RM Pandey, Rohit Bhatia, Ashima Nehra
DOI:10.4103/aian.AIAN_456_16  
Background: Depression is one of the most researched emotional responses after stroke and shows that the emotional impact of aphasia can have a marked negative impact on recovery, response to rehabilitation, and psychosocial adjustment. There is an evident dearth of validated instruments to assess depression in people with aphasia including Hindi, the national language of the country. Aims: The aim of this study was to translate and adapt the original English version of widely used hospital version of Stroke Aphasia Depression Questionnaire (SADQ-10) to Hindi. Subjects and Methods: English version of SADQ-10 was translated and adapted for the use in Hindi-speaking population in concordance to the WHO guidelines. Statistical Analysis Used: The intraclass correlation coefficient (ICC) analysis of the data was performed using SPSS, version 16, to compute the test–retest reliability. Results: The Hindi version of SADQ-10 yielded an overall high test–retest reliability (ICC = 0.91) as well as internal consistency (α = 0.98), which in turn were comparable to the original instrument in English. Conclusions: SADQ10-Hindi may assist the identification of depressed mood in patients with speech and language impairment in an Indian population as well. It is an easy to administer and quick test which can be used by health-care professionals in a hospital- or community-based settings.
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LETTERS TO THE EDITOR Top

Turf wars in stroke medicine: Why should patients suffer p. 156
Shriram Varadharajan
DOI:10.4103/0972-2327.205777  
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Endovascular stroke treatment: Is it “everybody's cup of tea?” p. 157
Kamble Rajeev, Moudgil Sandeep, Gupta Vivek
DOI:10.4103/0972-2327.205781  
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Paradigm shift in stroke prevention: Need of the hour p. 158
Pushpendra Nath Renjen
DOI:10.4103/aian.AIAN_18_17  
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Direct mechanical thrombectomy with thromboaspiration in cerebral venous sinus thrombosis p. 160
Vikram Bohra, Romnesh deSouza, Vivek Karan, Vikram Huded
DOI:10.4103/0972-2327.205767  
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Successful revascularization of acute middle cerebral artery occlusion by intravenous thrombolysis while on apixaban p. 161
Vivek K Nambiar, TS Dhanya, Amrutha V Ajai
DOI:10.4103/aian.AIAN_422_16  
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Right- versus left-onset Parkinson's disease: Other psychometric parameters p. 162
Yassar Abdullah S Alamri
DOI:10.4103/aian.AIAN_62_17  
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A case of Kennedy's disease from India p. 163
Ayush Dubey, Rahul Jain, Ajoy Sodani, Dinesh Chouksey
DOI:10.4103/0972-2327.205778  
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Molecular diagnosis of limb-girdle muscular dystrophy type 2A by next-generation sequencing p. 164
Clara Gómez-González, Maria Isabel Esteban-Rodríguez, Yolanda Ruano, Elena Vallespín, Pablo Lapunzina, Paloma Martínez, Samuel I Pascual, Jesús Molano, Carmen Prior
DOI:10.4103/aian.AIAN_432_16  
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Carbamazepine: A symptomatic treatment of the paresthesiae associated with Lhermitte's sign p. 166
Karl Ekbom
DOI:10.4103/aian.AIAN_21_17  
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Bupropion and iron for restless leg syndrome: Do they have efficacy similar to ropinirole? p. 166
Samir Kumar Praharaj
DOI:10.4103/0972-2327.205775  
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Response to reader's queries p. 167
Kirti Vishwakarma, Juhi Kalra, Ravi Gupta, Mukesh Sharma, Taruna Sharma
DOI:10.4103/aian.AIAN_12_17  
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Piloerection: A rare ictal phenomenon – Case report and review of literature p. 169
Samhita Panda, Chandrashekhar Agarwal, Ankkita Sharma
DOI:10.4103/aian.AIAN_427_16  
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An eminently treatable dropped head syndrome p. 172
Jacob George, L Vinitha, V Beena
DOI:10.4103/aian.AIAN_476_16  
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