Mobile application as a complementary tool for differential diagnosis in Neuro-ophthalmology: A multicenter cross-sectional study.

Purpose: Drawing differential diagnoses to a Neuro-ophthalmology clinical scenario is a difficult task for a neurology trainee. The authors conducted a study to determine if a mobile application specialized in suggesting differential diagnoses from clinical scenarios can complement clinical reasoning of a neurologist in training. Methods: A cross-sectional multicenter study was conducted to compare the accuracy of neurology residents versus a mobile medical app (Neurology Dx) in drawing a comprehensive list of differential diagnoses from Neuro-ophthalmology clinical vignettes. The differentials generated by residents and the App were compared with the Gold standard differential diagnoses adjudicated by experts. The prespecified primary outcome was the proportion of correctly identified high likely gold standard differential diagnosis by residents and App. Results: Neurology residents (n = 100) attempted 1500 Neuro-ophthalmology clinical vignettes. Frequency of correctly identified high likely differential diagnosis by residents was 19.42% versus 53.71% by the App (P < 0.0001). The first listed differential diagnosis by the residents matched with that of the first differential diagnosis adjudicated by experts (gold standard differential diagnosis) with a frequency of 26.5% versus 28.3% by the App, whereas the combined output of residents and App scored a frequency of 41.2% in identifying the first gold standard differential correctly. The residents correctly identified the first three and first five gold standard differential diagnosis with a frequency of 17.83% and 19.2%, respectively, as against 22.26% and 30.39% (P < 0.0001) by the App. Conclusion: A ruled based app in Neuro-ophthalmology has the potential to complement a neurology resident in drawing a comprehensive list of differential diagnoses.

Quality of Life and Its Determinants in Adult Drug Refractory Epilepsy Patients Who Were Not Candidates for Epilepsy Surgery: A Correlational Study.

BACKGROUND AND PURPOSE: This study was performed to elucidate quality of life (QOL) and its determinants in adult drug refractory epilepsy (DRE) patients who were not candidates for epilepsy surgery. METHODS: A correlational study was performed at the center of excellence, epilepsy between July 2014 to June 2016. All consecutive DRE patients who were not candidates for epilepsy surgery were enrolled. The outcomes were QOL, assessed using the quality of life inventory in epilepsy-31 items (QOLIE-31) inventory and the correlation of QOL with epilepsy-related variables like seizure severity and frequency. We also compared current QOL with QOL during the pre-surgical evaluation to strengthen our study outcome. RESULTS: A total of 129 adult patients were enrolled over two years. The mean age was 26.5 ± 6.7 years and male: female ratio was 3: 1. The mean age at epilepsy onset was 9.6 ± 6.6 years and mean duration of epilepsy was 14.9 ± 7.5 years. There was lower seizure frequency than during pre-surgical evaluation in 37.2% of patients, while in 62.8% the seizure frequency remained the same or was higher. Nine (6.98%) patients became seizure free. In comparison to QOL status during the pre-surgical evaluation, there was statistically significant worsening of QOL in all domains (p < 0.01). Seizure severity significantly correlated with almost all QOL domains (p ≤ 0.01), while seizure frequency significantly correlated with only the single domain of overall QOL (p = 0.03). CONCLUSIONS: The QOL of DRE patients who were not candidates for epilepsy surgery worsened relative to the QOL during the pre-surgical evaluation period. Seizure severity significantly correlated with QOL, but seizure frequency did not.

Utility of a questionnaire tool (QUARAS) for localizing and lateralizing seizures in the epilepsy monitoring unit (EMU).

OBJECTIVES: An accurate description of the seizure semiology improves the recognition of the ictal onset zone and helps in hypothesizing the possible epileptogenic zone (EZ). Semiology based on a reliable description of seizures may be as good as investigative modalities, as has been shown by numerous studies. The main objective of this study was to apply a questionnaire-tool for auras and semiology (QUARAS) in refractory epilepsy cohort and compare its yield to that of standard history-taking. METHODS: A drug refractory epilepsy cohort of 139 subjects was selected, based on inclusion and exclusion criteria. All subjects underwent routine history-taking, and a structured interview with QUARAS (in Hindi language) about 3-6 months later when they were admitted for pre-surgical work-up (Video-EEG, MRI, SPECT and PET), by an epilepsy nurse. Seizures were localised and lateralised at the each step separately, in a blinded manner; concordance with the final hypothesis was checked, after the epilepsy-surgery case-conference, and statistical significance of the difference calculated. RESULTS: Auras were reported in significantly more number of patients after administration of QUARAS (p<0.001); there was also higher concordance between the final hypothesis and the localization and lateralization based on QUARAS than an unstructured history (p<0.001). CONCLUSION: Administering a structured questionnaire in the native language of patients by trained personnel leads to better localisation and lateralisation and may help arrive at a hypothesis about the EZ.

Investigation of mitochondrial DNA variations among Indian Friedreich's ataxia (FRDA) patients.

OBJECTIVE: The loss of function mutations (biallelic) in frataxin (FXN) has primarily been implicated in Friedreich's ataxia (FRDA), an autosomal recessive cerebellar ataxia. The protein product of FXN is a nuclear-encoded mitochondrial protein required for the biogenesis of iron- clusters (Fe-S). FRDA is characterized by neurological and non-neurological features which show variable expression in affected individuals. An inverse relationship has been demonstrated between GAA repeat size and age at onset and explains 50% variability of the age at onset. MtDNA variations and haplogroups could be one of the contributory factors to explain the remaining heterogeneity in FRDA, since mitochondrial oxidative stress is thought to be involved in the pathogenesis of FRDA. METHODS: In our study, targeted resequencing of the D-loop and coding region of mitochondrial genes (ND1-6 and ATP) was conducted in 30 genetically confirmed FRDA patients and 62 ethnicity-matched unrelated healthy controls to identify the functionally important mtDNA variations and to trace the mitochondrial lineage of Indian FRDA patients. Cumulative mitochondrial SNP scores were computed for the identified variations in the functional region and haplogroups were determined by Haplogrep. RESULTS: A significantly higher load of overall mitochondrial variations (with a trend toward the coding region) per individual was noted among FRDA cases rather than controls (p-value<0.03). A non-synonymous variation (p. L237M) in ND2 was over-represented among FRDA cases (p-value 0.04). This variation has a reported association with longevity and myocardial infarction. We also observed over-representation of H haplogroup (Caucasian mitochondrial haplogroup) among FRDA patients. We have not observed the influence of mitochondrial variations and haplogroup upon age at onset of FRDA. CONCLUSIONS: Overall, our study identifies the functionally important variations and mitochondrial lineage of Indian FRDA cases and, that underscores the importance of studying the role of mitochondrial genome variations in FRDA.

Effect of reduction of antiepileptic drugs in patients with drug-refractory epilepsy.

PURPOSE: The present study was conducted with the aim of evaluating the effects of reducing the number of antiepileptic drugs (AEDs) administered to patients with drug-refractory epilepsy (DRE) during their admission and document any change in seizure frequency in subsequent follow up. METHODS: A total of 962 patients with DRE who were admitted to the neurology wards waiting for connection to video EEG were recruited for this prospective study. After their admission to the neurology ward, modifications in the number and dosage of AEDs were done with a target of a maximum of three AEDs in every patient. Drug tapering was done using a standardized protocol. The primary outcome was the change in seizure frequency in the follow-up period of 6 months. Secondary outcome measures were the adverse event profile (AEP) and the quality of life (QOL). RESULTS: Of the 1134 patients screened, 962 patients gave consent to participate in the study. The mean number of AEDs received by each patient was 4.24. After the tapering following a standardized protocol each patient received a mean of 2.65 AEDs per patient. In 82.70% patients with DRE, there was either a reduction or no change in seizure frequency in the subsequent 6 months follow up. There was a significant reduction in the AEP score after the reduction in the number of AEDs (P = 0. 001). CONCLUSION: Our study proves that optimization of reduction of the number of AED's in patients with DRE leads to reduction or no change in seizure frequency with a significant decrease in adverse effects.

Risk factors and etiologies of ischemic strokes in young patients: a tertiary hospital study in north India.

BACKGROUND AND PURPOSE: Stroke in young adults has a special significance in developing countries, as it affects the most economically productive group of the society. We identified the risk factors and etiologies of young patients who suffered ischemic strokes and were admitted to a tertiary referral hospital in North India. METHODS: A retrospective review of case records from patients with ischemic stroke in the age range of 18-45 years was conducted from 2005 to 2010. Data regarding patients' clinical profiles, medical histories, diagnostic test results, and modified Rankin Scale scores at hospital discharge were examined. Stroke subtyping was conducted in accordance with the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. RESULTS: Of the 2,634 patients admitted for ischemic stroke, 440 (16.7%) were in the 18-45 year age range and the majority (83.4%) were male. The most common risk factors were hypertension (34.4%) and dyslipidemia (26.5%). The most common subtype of stroke was undetermined (57%), followed by other determined causes (17.3%). Among the category of undetermined etiology, incomplete evaluation was the most common. Most of the patients demonstrated good functional outcomes. CONCLUSIONS: Young adults account for 16.7% of all stroke patients in North India. Risk factors are relatively prevalent, and a high proportion of the patients are categorized under undetermined and other determined causes. The results highlight the needs for aggressive management of traditional risk factors and extensive patient work-ups to identify stroke etiology in India.

Autoimmune encephalitis: A potentially reversible cause of status epilepticus, epilepsy, and cognitive decline.

OBJECTIVES: To review clinical characteristics and response to immunomodulation therapy in autoimmune encephalitis presenting with status epilepticus (SE), epilepsy, and cognitive decline. DESIGN: Observational, prospective case series. SETTING: All India Institute of Medical Sciences, New Delhi, India. MATERIALS AND METHODS: Prospective analysis of 15 patients, who presented with SE, epilepsy, cognitive decline, and other neurological symptoms with positive autoantibodies. Demographic and clinical characteristics were recorded. Brain magnetic resonance imaging (MRI), cerebrospinal-fluid analysis (CSF), and tumor screening were done periodically. Treatment received and responses (categorized as per patients and treating doctor's information) were noted. RESULTS: There were 15 (males = 10) patients of autoimmune encephalitis. The mean age of presentation was 24 years (range: 2-64 years). The most common onset was subacute (64%) and four (29%) patients presented as SE. Predominant clinical presentations were seizures (100%) almost of every semiology. CSF was done in 10 patients; it was normal in 60%. Brain MRI was done in all patients, in six (40%) it was normal, six (40%) showed T2W and FLAIR hyperintensities in bilateral limbic areas. Antibodies found were the N-methyl-D-aspartate receptor antibody in seven (50%), voltage-gated potassium channel antibody in five (36%), two of antiglutamic acid decarboxylase, and one patient with double stranded DNA (dsDNA) antibodies. None showed evidence of malignancy. Patients received immunotherapy, either steroids, intravenous immunoglobulin, or both. Follow-up showed significant improvement in majority of cases, neither further seizures nor relapse in nine (67%) cases. One death occurred, due to delayed presentation. CONCLUSIONS: Uncommon but potentially reversible causes of SE, epilepsy, and cognitive decline may be immune-related and high index of suspicion will prevent missing the diagnosis.

Premorbid nutrition and short term outcome of stroke: a multicentre study from India.

BACKGROUND: Little is known about the impact of premorbid undernutrition on stroke outcome in developing countries. AIM: To study the impact of premorbid undernutrition status, measured by the Subjective Global Assessment (SGA) tool, on short term stroke outcome. METHODS: First ever stroke patients admitted to six major hospitals in North and South India participated in this study from 1 March 2008 to 30 September 2009. The SGA tool was administered within 48 h of stroke onset, and 6 months premorbid nutritional status was rated as well nourished (A rating) and undernourished (B and C ratings) using this tool. Stroke outcome was assessed after 30 days using the modified Rankin scale (mRs), and a mRs score >3 was defined as a poor outcome. Statistical analyses were performed using SPSS Statistics V.17.0. RESULTS: Of 477 patients enrolled, 448 patients were included in the analyses. Mean age was 58.1±13.7 years (range 16-96) and 281 (62.7%) patients were men. At admission, premorbid undernutrition was found in 121 (27.2%) patients. Older age (OR 4.99, CI 1.26 to 19.64, p=0.021), hypertension (OR 1.99, CI 1.04 to 3.79, p=0.037) and patients from Andhra Pradesh State (OR 1.87, CI 1.05 to 3.32, p=0.032) were predictors of undernutrition in multiple logistic regression analysis. Premorbid undernutrition (OR 1.99, CI 1.20 to 3.31, p=0.007) and length of hospital stay (OR 3.41, CI 1.91 to 6.06, p<0.0001) were the independent predictors of poor outcome in the multiple logistic regression model. CONCLUSIONS: High rates of premorbid undernutrition in stroke patients were found. Age, hypertension and patients from Andhra Pradesh State were predictors of premorbid undernutrition. Premorbid undernutrition was associated with poor stroke outcome. The results provide opportunities for primary prevention and improving stroke outcome.