Neuropsychological Rehabilitation for Epilepsy in India: Looking Beyond the Basics.

BACKGROUND: Neuropsychological Rehabilitation (NR) helps manage cognitive deficits in epilepsy. As internationally developed programs have limited applicability to resource-limited countries, we developed a program to bridge this gap. This 6-week caregiver-assisted, culturally suitable program has components of (1) psychoeducation, (2) compensatory training, and, (3) cognitive retraining and is called EMPOWER (Indigenized Home Based Attention and Memory Rehabilitation Program for Adult Patients with Drug Refractory Epilepsy). Its efficacy needs to be determined. METHODS: We carried out an open-label parallel randomized controlled trial. Adults aged 18-45 years with Drug Refractory Epilepsy (DRE), fluency in Hindi and or English, with impaired attention or memory (n = 28) were randomized to Intervention Group (IG) and Control Group (CG). The primary outcomes were objective memory (Auditory Verbal Learning Test), patient and caregiver reported everyday memory difficulties (Everyday Memory Questionnaire-Revised), number of memory aids in use, depression (Hamilton Depression Rating Scale), anxiety (Hamilton Anxiety Rating Scale) and quality of life (Quality of Life in Epilepsy-31). Intention to treat was carried out for group analysis. In the absence of norms necessary for computing Reliable Change Indices (RCIs), a cut-off of +1.0 Standard Deviation (SD) was utilized to identify clinically meaningful changes in the individual analysis of objective memory. A cut-off of 11.8 points was used for quality of life. Feedback and program evaluation responses were noted. RESULTS: The majority of the sample comprised DRE patients with temporal lobe epilepsy who had undergone epilepsy surgery. Group analysis indicated improved learning (p = 0.013), immediate recall (p = 0.001), delayed recall (p < 0.001), long-term retention (p = 0.031), patient-reported everyday memory (p < 0.001), caregiver-reported everyday memory (p < 0.001), anxiety (p = 0.039) and total quality of life (p < 0.001). Individual analysis showed improvement in 50 %, 64 %, 71 %, 57 %, and 64 % of patients on learning, immediate recall, delayed recall, long-term retention, and total quality of life respectively. Despite improvements, themes indicative of a lack of awareness and understanding of cognitive deficits were identified. Overall, the program was rated favorably by patients and caregivers alike. CONCLUSION: NR shows promise for patients with DRE, however larger studies are warranted. The role of cognition in epilepsy needs to be introduced at the time of diagnosis to help lay the foundation for education and acceptance.

MoCA in five Indian languages: A brief screening tool to diagnose dementia and MCI in a linguistically diverse setting.

INTRODUCTION AND OBJECTIVES: Early dementia diagnosis in low and middle-income countries (LMIC) is challenging due to limited availability of brief, culturally appropriate, and psychometrically validated tests. Montreal Cognitive Assessment (MoCA) is one of the most widely used cognitive screening tests in primary and secondary care globally. In the current study, we adapted and validated MoCA in five Indian languages (Hindi, Bengali, Telugu, Kannada, and Malayalam) and determined the optimal cut-off points that correspond to screening for clinical diagnosis of dementia and MCI. METHODS: A systematic process of adaptation and modifications of MoCA was fulfilled. A total of 446 participants: 214 controls, 102 dementia, and 130 MCI were recruited across six centers. RESULTS: Across five languages, the area under the curve for diagnosis of dementia varied from 0.89 to 0.98 and MCI varied from 0.73 to 0.96. The sensitivity, specificity and optimum cut-off scores were established separately for five Indian languages. CONCLUSIONS: The Indian adapted MoCA is standardized and validated in five Indian languages for early diagnosis of dementia and MCI in a linguistically and culturally diverse population.

Picture-naming test for a linguistically diverse population with cognitive impairment and dementia.

BACKGROUND: Picture-naming tests (PNTs) evaluate linguistic impairment in dementia due to semantic memory impairment, impaired lexical retrieval or perceptual deficits. They also assess the decline in naming impairment at various stages of dementia and mild cognitive impairment (MCI) that occurs due to progressive cognitive impairment. With the increasing numbers of people with dementia globally, it is necessary to have validated naming tests and norms that are culturally and linguistically appropriate. AIMS: In this cross-sectional study we harmonized a set of 30 images applicable to the Indian context across five languages and investigated the picture-naming performance in patients with MCI and dementia. METHODS & PROCEDURES: A multidisciplinary expert group formed by the Indian Council of Medical Research (ICMR) collaborated towards developing and adapting a picture naming test (PNT) known as the ICMR-PNT in five Indian languages: Hindi, Bengali, Telugu, Kannada and Malayalam. Based on cross-cultural adaptation guidelines and item-wise factor analysis and correlations established separately across five languages, the final version of the ICMR-PNT test was developed. A total of 368 controls, 123 dementia and 128 MCI patients were recruited for the study. Psychometric properties of the adapted version of the ICMR-PNT were examined, and sensitivity and specificity were examined. OUTCOMES & RESULTS: The ICMR-PNT scores in all languages combined were higher in controls compared with patients with dementia and MCI (F2, 615 = 139.85; p < 0.001). Furthermore, PNT scores for MCI was higher in comparison with patients with dementia in all languages combined (p < 0.001). The area under the curve across the five languages ranged from 0.81 to 1.00 for detecting dementia. There was a negative correlation between Clinical Dementia Rating (CDR) and ICMR-PNT scores and a positive correlation between Addenbrooke's Cognitive Examination-III (ACE-III) and ICMR-PNT scores in control and patient groups. CONCLUSIONS & IMPLICATIONS: The ICMR-PNT was developed by following cross-cultural adaptation guidelines and establishing correlations using item-wise factor analysis across five languages. This adapted PNT was found to be a reliable tool when assessing naming abilities effectively in mild to moderate dementia in a linguistically diverse context. WHAT THIS PAPER ADDS: What is already known on this subject Picture-naming evaluates language impairment linked to naming difficulties due to semantic memory, lexical retrieval or perceptual disturbances. As a result, picture naming tests (PNTs) play an important role in the diagnosis of dementia. In a heterogeneous population such as India, there is a need for a common PNT that can be used across the wide range of languages. What this study adds to existing knowledge PNTs such as the Boston Naming Test (BNT) were developed for the educated, mostly English-speaking, Western populations and are not appropriate for use in an Indian context. To overcome this challenge, a PNT was harmonized in five Indian languages (Hindi, Bengali, Telugu, Kannada and Malayalam) and we report the patterns of naming difficulty in patients with MCI and dementia. The ICMR-PNT demonstrated good diagnostic accuracy when distinguishing patients with mild to moderate dementia from cognitively normal individuals. What are the potential or actual clinical implications of this work? With the growing number of persons suffering from Alzheimer's disease and other forms of dementia around the world, its critical to have culturally and linguistically relevant naming tests and diagnosis. This validated ICMR-PNT can be used widely as a clinical tool to diagnose dementia and harmonize research efforts across diverse populations.

Suspend or amend? Randomized controlled trial on neuropsychological rehabilitation for epilepsy: A COVID-19 impact.

COVID-19 caused devastating effects of human loss and suffering along with disruption in clinical research, forcing reconceptualization and modification of studies. This paper attempts to outline the steps followed and detail the modifications undertaken to deal with the impacts of the pandemic on the first ongoing randomized controlled trial on effectiveness of neuropsychological rehabilitation in adult patients with drug-resistant epilepsy in India. All modifications were based on evolving guidelines and circumstantial context and were planned, reviewed and approved by important stakeholders. Results obtained from the trial need to be interpreted and analysed within this context. These modifications have implications for wider outreach of neuropsychology services in India.

Validation of ICMR Neurocognitive Toolbox for Dementia in the Linguistically Diverse Context of India.

Objectives: The growing prevalence of dementia, especially in low- and middle-income countries (LMICs), has raised the need for a unified cognitive screening tool that can aid its early detection. The linguistically and educationally diverse population in India contributes to challenges in diagnosis. The present study aimed to assess the validity and diagnostic accuracy of the Indian Council of Medical Research-Neurocognitive Toolbox (ICMR-NCTB), a comprehensive neuropsychological test battery adapted in five languages, for the diagnosis of dementia. Methods: A multidisciplinary group of experts developed the ICMR-NCTB based on reviewing the existing tools and incorporation of culturally appropriate modifications. The finalized tests of the major cognitive domains of attention, executive functions, memory, language, and visuospatial skills were then adapted and translated into five Indian languages: Hindi, Bengali, Telugu, Kannada, and Malayalam. Three hundred fifty-four participants were recruited, including 222 controls and 132 dementia patients. The sensitivity and specificity of the adapted tests were established for the diagnosis of dementia. Results: A significant difference in the mean (median) performance scores between healthy controls and patients with dementia was observed on all tests of ICMR-NCTB. The area under the curve for majority of the tests included in the ICMR-NCTB ranged from 0.73 to 1.00, and the sensitivity and specificity of the ICMR-NCTB tests ranged from 70 to 100% and 70.7 to 100%, respectively, to identify dementia across all five languages. Conclusions: The ICMR-NCTB is a valid instrument to diagnose dementia across five Indian languages, with good diagnostic accuracy. The toolbox was effective in overcoming the challenge of linguistic diversity. The study has wide implications to address the problem of a high disease burden and low diagnostic rate of dementia in LMICs like India.

Clinical Features, Gender Differences, Disease Course, and Outcome in Neuromyelitis Optica Spectrum Disorder.

INTRODUCTION: Neuromyelitis optica spectrum disorder (NMOSD) is an astrocytopathy with a predilection for the optic nerve, spinal cord, and brainstem. In this ambispective study, we evaluate clinical characteristics, responses to therapy, and disability outcomes in patients with NMOSD. METHODS: Patients diagnosed as NMOSD and following up for at least 1 year at a tertiary care center in India were recruited. Patient data were collected ambispectively from January 2012 until December 2018. RESULTS: A total of 106 patients (29M/77F) with NMOSD were evaluated. The mean age of onset was 29 (±11.6) years. About 77 patients (72.64%) were positive for the AQP4 antibody. Age of onset was higher for those presenting with an opticospinal syndrome (34.2 years) as compared to either isolated longitudinally extensive transverse myelitis (LETM) (30 years) or optic neuritis (ON) (25.3 years). The most common syndrome at onset was LETM in 57 patients (53.77%) followed by ON in 31 patients (29.24%). Azathioprine was the most common immunotherapy (83.96%) prescribed followed by rituximab (7.54%) and mycophenolate mofetil (1.88%). There was a significant decrease in the number of relapses post-azathioprine (P < 0.001). Out of 67 patients with ON, 21 (31.34%) had complete recovery while 17 (25.37%) patients had a severe deficit at a 3-month follow-up. Out of 92 patients with a motor deficit, 49 (53.26%) patients had a partial motor deficit at a 6-month follow-up. The severe visual deficit at baseline and female gender predicted poor visual and motor recovery, respectively. CONCLUSION: This is the largest descriptive study on patients with NMOSD from India. Relapse rates were similar irrespective of the clinical presentation, age, gender, and disease course. Treatment with immunosuppressive treatment significantly affected the disease course.

Clinical and laboratory evidence of Lyme disease in North India, 2016-2019.

BACKGROUND: Lyme disease is endemic to parts of the Americas, Europe and Asia. However, only a handful of sporadic cases have been reported from India. In this study, we systematically evaluated the clinical and epidemiological features of Lyme disease in North India. METHOD: All samples were tested by using the standard two-tiered testing algorithm (STTA). Paired serum and cerebrospinal fluid (CSF) were used for demonstrating Borrelia burgdorferi specific intrathecal IgG antibody synthesis (AI). In addition, a commercial tick-borne bacterial flow chip (TBFC) system and a real-time PCR were also used to detect Borrelia species and Anaplasma phagocytophilum in patients who were positive by STTA. RESULTS: The diagnosis of Lyme disease was confirmed in 18 (7.14%) of the 252 clinically suspected cases by STTA. Neurological involvement was reported in 14 (77.78%) patients, whereas joint and heart involvement was reported in five (27.78%) and three (16.67%) patients, respectively. Lymphocytic pleocytosis (median 37.5 cells/mm3; range 12-175 cells/mm3) in the CSF was seen in 11 of 14 Lyme neuroborreliosis (LNB) patients. Intrathecal production of Borrelia specific IgG antibodies was demonstrated in 9 (64.28%, n = 14) patients, a highly specific finding for neuroborreliosis. Two patients (11.11%) were also found to be co-infected with human granulocytic anaplasmosis. CONCLUSIONS: The results of this study show clinical and laboratory evidence of endemic Lyme disease in North India and thus, highlight the importance for travel medicine practitioners and physicians to evaluate for Lyme disease in patients with compatible symptoms and a history of travel to tick risk areas.

Recurrent Neurocysticercosis: Not So Rare.

BACKGROUND: Solitary cysticercus granuloma (SCG) appearing as a single ring-enhancing lesion (SREL) is the most frequently encountered imaging finding in patients of neurocysticercosis (NCC) in India and during follow-up, most of SCGs resolve with or without calcifications. Recurrent SCG have been rarely reported. OBJECTIVES: The aim of our study is to report the incidence of recurrent SCG in a cohort of patients with SCG and postulate the hypothesis. MATERIALS AND METHODS: This retrospective study included 278 patients with SCG meeting the criteria of NCC. Their medical records and imaging studies were analyzed. RESULTS: Out of 278 patients, 119 patients with SCG meeting the criteria of NCC with follow-up imaging were included. 15 (12.61%) had recurrent NCC and 104 (87.4%) patients did not have any recurrence during a median follow-up of 14.23 months (range; 0.24 - 113.3) and 25.26 months (range; 3.09- 98.11) respectively. Out of 15 recurrent NCC cases, ten patients had documented imaging resolution or partial regression of previous lesion followed by occurrence of new SCG in the same location, three patients had change in morphology of lesion from solitary discrete REL to solitary conglomerate REL secondary to development of new cysticercus granuloma adjacent to old lesion patients had recurrent lesions adjacent to previous lesion and two patients had new SCG in different locations following regression of old SCGs. CONCLUSION: Recurrent SCGs are not uncommon in NCC and recurrence is more likely to occur at the site of initial infection and therefore may be mistaken for persistent infection or other granulomatous lesions.

Bilingualism and Its Implications for Neuropsychological Evaluation.

OBJECTIVE: In the background of a large population of bilinguals globally, the study aimed to develop standards of neuropsychological testing in the context of bilingualism. Because bilingualism is known to affect cognitive processes, bilinguals and monolinguals were compared on their performance on cognitive tests, to investigate the possibility of the need for separate normative data for the two groups. METHOD: A comprehensive neuropsychological test battery, standardized across five Indian languages: the Indian Council of Medical Research-Neuro Cognitive Tool Box (ICMR-NCTB) was administered to 530 participants (267 monolingual and 263 bilinguals matched for age and education). A systematic method of testing cognition in bilinguals was developed; to identify the appropriate language for testing, ensure language proficiency of examiner, and to interpret the bilingual responses. Additionally, the performance of bilinguals on the ICMR-NCTB was compared with monolinguals. RESULTS: Cognitive testing in the bilingual context was performed in the most proficient language of the participants, by examiners well versed with the language. Results from the language-based tests suggested that the frequent occurrence of borrowed- and language-mixed words required consideration while scoring. The reported bilingual effect on cognitive processes did not reflect as differences in the performance between bilinguals and monolinguals. CONCLUSIONS: Observations from the study provide robust recommendations for neuropsychological testing in the context of bilingualism. Results indicate that separate normative data may not be required for bilinguals and monolinguals. The study will be relevant and provide a reference framework to address similar issues in the large population of bilinguals in other societies.

Multilocus Sequence Typing of Clinical Isolates of Cryptococcus from India.

Cryptococcosis is a life-threatening infection caused by Cryptococcus neoformans and C. gattii species complex. In the present study, to understand the molecular epidemiology of 208 clinical isolates of Cryptococcus from different parts of India, multilocus sequence typing (MLST) using ISHAM MLST consensus scheme for C. neoformans/C. gattii species complex was used. MLST analysis yielded a total of 10 Sequence Types (STs)-7 STs for C. neoformans and 3 for C. gattii species complex. The majority of isolates identified as C. neoformans belonged to molecular type VNI with predominant STs 31 and 93. Only 3 isolates of C. gattii species complex were obtained, belonging to ST58 and ST215 of VGI and ST69 of VGIV. Phylogenetic analysis revealed less diversity among the clinical Indian isolates compared to the global MLST database. No association between prevalent STs and HIV status, geographical origin or minimum inhibitory concentration (MIC) could be established.

A Screening Tool to Detect Stroke Aphasia: Adaptation of Frenchay Aphasia Screening Test (FAST) to the Indian Context.

BACKGROUND: Aphasia is a common consequence of stroke. To optimize recovery, it becomes critical as there are early identification and treatment of language deficits. The rising burden of stroke aphasia and lack of screening tools in the Indian context necessitates the need for a screening tool. OBJECTIVE: We aimed to adapt and validate the Frenchay Aphasia Screening Test (FAST) to the Indian context in two widely spoken Indian languages, Telugu and Kannada, for the literate and illiterate population. METHODS: A systematic process of adaptation and culturally appropriate modifications of the original FAST were done in 116 healthy controls and 115 patients. The validity of the adapted test was established. RESULTS: The optimum cut-off values for detecting aphasia in our sample ranged from 25 to 25.5 (literate) and 13.5 to 15.5 (illiterate) with high sensitivity and specificity. There was also a significant correlation between aphasia scores for adapted FAST and the Western Aphasia Battery (WAB), establishing good convergent validity. DISCUSSION: Results of the adaptation and validation of two Indian versions of FAST, suggest that it is an easy-to-use screening measure for detecting stroke-related language disabilities. The psychometric properties of the Indian version of FAST met the standardised requirements for adaptation and validation. CONCLUSIONS: The Indian version of FAST was found to be a reliable and valid bedside screening tool for aphasia in stroke patients. We aim that this study will facilitate the use of the test across other Indian languages and a large clinical population in the future.

Seizure-related injuries in inadequately treated epilepsy patients: A case-control study.

PURPOSE: To compare epilepsy-related injuries in untreated or inadequately treated patients and patients on adequate treatment. METHODS: In a cross-sectional case-control study, seizure-related injuries in patients who were either on no treatment or inadequate treatment were compared with another group of patients receiving appropriate evidence-based epilepsy treatment. The inadequately treated patients or 'cases' were drawn from an outreach epilepsy clinic while the adequately treated patients or 'controls' were recruited from a tertiary care facility providing comprehensive epilepsy management. RESULTS: The odds of injury were eight times higher in inadequately treated patients or cases compared to the adequately treated patients or controls. After adjusting for gender, epilepsy duration, seizure frequency, current medication, and number of AEDs, the odds of injury were 15. 8 times higher in the cases. Major injuries such as burns, fractures, and tooth injuries were also higher in the cases. CONCLUSION: Untreated or inadequately treated epilepsy patients have a significantly higher risk of injuries. With adequate treatment, some of the risks of injury can be mitigated.

Application of Stem Cells in Stroke: A Multifactorial Approach.

Stroke has a debilitating effect on the human body and a serious negative effect on society, with a global incidence of one in every six people. According to the World Health Organization, 15 million people suffer stroke worldwide each year. Of these, 5 million die and another 5 million are permanently disabled. Motor and cognitive deficits like hemiparesis, paralysis, chronic pain, and psychomotor and behavioral symptoms can persist long term and prevent the patient from fully reintegrating into society, therefore continuing to add to the costly healthcare burden of stroke. Regenerative medicine using stem cells seems to be a panacea for sequelae after stroke. Stem cell-based therapy aids neuro-regeneration and neuroprotection for neurological recovery in patients. However, the use of stem cells as a therapy in stroke patients still needs a lot of research at both basic and translational levels. As well as the mode of action of stem cells in reversing the symptoms not being clear, there are several clinical parameters that need to be addressed before establishing stem cell therapy in stroke, such as the type of stem cells to be administered, the number of stem cells, the timing of dosage, whether dose-boosters are required, the route of administration, etc. There are upcoming prospects of cell-free therapy also by using exosomes derived from stem cells. There are several ongoing pre-clinical studies aiming to answer these questions. Despite still being in the development stage, stem cell therapy holds great potential for neurological rehabilitation in patients suffering from stroke.

Systematic Development of Structured Semi-interactive Stroke Prevention Package for Secondary Stroke Prevention.

BACKGROUND: Lack of compliance to medication and uncontrolled risk factors are associated with increased risk of recurrent stroke and acute coronary syndrome in patients with recent stroke. Multimodal patient education may be a strategy to improve the compliance to medication and early adoption of nonpharmacological measures to reduce the vascular risk factor burden in patients with stroke. We thus aim to develop multilingual short messaging services (SMS), print, and audio-visual secondary stroke prevention patient education package. The efficacy of the package will be tested in a randomized control trial to prevent major cardiovascular and cerebrovascular events. METHODS: In the formative stage, intervention materials (SMS, video, and workbook) were developed. In the acceptability stage, the package was independently assessed and modified by the stakeholders involved in the stroke patient care and local language experts. The modified stroke prevention package was tested for implementation issues (implementation stage). RESULTS: Sixty-nine SMS, six videos, and workbook with 11 chapters with 15 activities were developed in English language with a mean ± SD SMOG index of 9.1 ± 0.4. A total of 355 stakeholders including patients (24.8%), caregivers (24.8%), doctors (10.4%), nurses (14.1%), local language experts (2.8%), physiotherapists (13.2%), and research coordinators (9.8%) participated in 10 acceptability stage meetings. The mean Patient Education Material Assessment Tool understandability score in all languages for SMS, video scripts, and workbook was 95.2 ± 2.6%, 95.2 ± 4.4%, and 95.3 ± 3.6%, respectively. The patients [n = 20, mean age of 70.3 ± 10.6 years and median interquartile range (IQR) baseline NIHSS 1 (0-3)] or the research coordinators (n = 2) noted no implementation issues at the end of 1 month. CONCLUSION: An implementable complex multilingual patient education material could be developed in a stepwise manner. The efficacy of the package to prevent major adverse cardiovascular events is being tested in the SPRINT INDIA study.

Standardising Dementia Diagnosis Across Linguistic and Educational Diversity: Study Design of the Indian Council of Medical Research-Neurocognitive Tool Box (ICMR-NCTB).

OBJECTIVES: While the burden of dementia is increasing in low- and middle-income countries, there is a low rate of diagnosis and paucity of research in these regions. A major challenge to study dementia is the limited availability of standardised diagnostic tools for use in populations with linguistic and educational diversity. The objectives of the study were to develop a standardised and comprehensive neurocognitive test battery to diagnose dementia and mild cognitive impairment (MCI) due to varied etiologies, across different languages and educational levels in India, to facilitate research efforts in diverse settings. METHODS: A multidisciplinary expert group formed by Indian Council of Medical Research (ICMR) collaborated towards adapting and validating a neurocognitive test battery, that is, the ICMR Neurocognitive Tool Box (ICMR-NCTB) in five Indian languages (Hindi, Bengali, Telugu, Kannada, and Malayalam), for illiterates and literates, to standardise diagnosis of dementia and MCI in India. RESULTS: Following a review of existing international and national efforts at standardising dementia diagnosis, the ICMR-NCTB was developed and adapted to the Indian setting of sociolinguistic diversity. The battery consisted of tests of cognition, behaviour, and functional activities. A uniform protocol for diagnosis of normal cognition, MCI, and dementia due to neurodegenerative diseases and stroke was followed in six centres. A systematic plan for validating the ICMR-NCTB and establishing cut-off values in a diverse multicentric cohort was developed. CONCLUSIONS: A key outcome was the development of a comprehensive diagnostic tool for diagnosis of dementia and MCI due to varied etiologies, in the diverse socio-demographic setting of India.

Quantitative Proteomic and Network Analysis of Differentially Expressed Proteins in PBMC of Friedreich's Ataxia (FRDA) Patients.

Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disorder caused by an expanded (GAA) trinucleotide repeat in the FXN gene. The extended repeats expansion results in reduced transcription and, thereby, decreased expression of the mitochondrial protein, frataxin. Given the ongoing drug trials, identification of reliable and easily accessible biomarkers for monitoring disease progression and therapeutic intervention is a foremost requirement. In this study, comparative proteomic profiling of PBMC proteins from FRDA patients and age- and gender-matched healthy controls was done using 2D-Differential in-Gel Electrophoresis (2D-DIGE). Protein-protein interaction (PPI) was analyzed using BioGRID and STRING pathway analysis tools. Using biological variance analysis (BVA) and LC/MS, we found eight differentially expressed proteins with fold change ≥1.5; p ≤ 0.05. Based on their cellular function, the identified proteins showed a strong pathological role in neuroinflammation, cardiomyopathy, compromised glucose metabolism, and iron transport, which are the major clinical manifestations of FRDA. Protein-protein network analysis of differentially expressed proteins with frataxin further supports their involvement in the pathophysiology of FRDA. Considering their crucial role in the cardiac and neurological complications, respectively, the two down-regulated proteins, actin α cardiac muscle 1 (ACTC1) and pyruvate dehydrogenase E1 component subunit ß (PDHE1), are suggested as potential prognostic markers for FRDA.

POEMS Syndrome: Indian Experience From a Tertiary-Care Institute.

INTRODUCTION: POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes) syndrome is a rare multisystem paraneoplastic syndrome characterized by peripheral neuropathy and monoclonal plasmacytosis. Retrospective institutional experiences from the Mayo Clinic as well as Chinese, European, and Japanese series have provided important insights into the characteristics and treatment of this disease, but Indian data are extremely limited. We retrospectively analyzed 49 cases from our institute including 10 patients who underwent autologous stem-cell transplantation (ASCT). PATIENTS AND METHODS: We analyzed clinical and laboratory characteristics, treatment details and outcome of all patients diagnosed with POEMS syndrome between 1993 and 2017. RESULTS: Complete medical records were available for 49 patients with a median age of 44 years. Male/female ratio was 38:11. Twenty patients (40.8%) had Eastern Cooperative Oncology Group performance status of 4. Before 2012, melphalan/prednisolone was the most common regimen provided, while bortezomib/dexamethasone and lenalidomide/dexamethasone were used later. Hematologic response was available for 40 patients, 15 (37.5%) of whom experienced complete response, 13 (32.5%) partial response, and 11 (27.5%) stable disease. The median modified Rankin score at baseline was 4 (range, 1-5), which improved to 3 (range, 1-5). Ten patients underwent consolidation ASCT after a median of 4 cycles of induction. Median melphalan dose was 140 mg/m2. Engraftment syndrome was observed in 4. After ASCT, all 10 patients experienced hematologic complete response and clinical improvement. CONCLUSION: This retrospective analysis provides important information on the clinical characteristics of POEMS syndrome in Indian patients, which will help the clinician's decision-making process.

Stroke-related education to emergency department staff: An acute stroke care quality improvement initiative.

BACKGROUND: Acute ischemic stroke therapy is time sensitive, and optimum treatment is missed due to pre-hospital and/or in-hospital delay. MATERIALS AND METHODS: A prospective observational (before and after) study was conducted for 1 year.The study period was defined as phase-I or pre-education phase, phase-II or immediate post-education phase, and phase-III or delayed post-education phase, with each phase lasting for 4months. All consecutive stroke patients presenting within 12 hours of stroke onset were enrolled. Baseline and outcome data including acute stroke care quality matrices and functional outcomes were collected. RESULTS: A total of 264 patients were enrolled. All acute stroke care quality matrices improved significantly (P ≤ 0.01) with a median door to imaging time (DTI) of 114, 35, and 47 minutes in the three phases consecutively. In phase-II, proportions of patients imaged within 25 minutes of arrival increased by 35%. Mean door to needle (DTN) time were 142 ± 49.7,63.7 ± 25.1, and 83.9 ± 38.1 minutes in the three consecutive phases. Patients with DTN < 60 minutes of arrival increased by 63%. Modified Rankin score (mRS) at 3 months improved significantly in all ischemic stroke patients (P = 0.04) and patients with mRS of 0-2 increased by 22%. CONCLUSIONS: Stroke education to emergency department (ED) staff is an effective method to improve acute stroke care.

Regional differences in ischemic stroke in India (north vs. south).

BACKGROUND: India is a large country with geographically diverse populations and varying risk factors. Identification of regional differences can improve healthcare policy decisions. AIM: To study regional differences in stroke between North and South India. METHODS: We analyzed data from the Indo-US Collaborative Stroke Project, a National Institute of Health-funded multicentre prospective study conducted in five academic centers in India with a US-based coordinating center. Risk factors, severity, mechanisms, management, complications, and outcomes among ischemic stroke patients were compared between North and South Indian centers. RESULTS: Of the 2066 patients enrolled from North (n = 1060) and South India (n = 1006), North Indian patients were significantly older with fewer men and had lower rates of diabetes (32.8% vs. 38.7%, p < 0.01), dyslipidemia (3.5% vs. 25.7%, p < 0.01), tobacco use (27% vs. 38%, p < 0.001), and alcohol use (30.1% vs. 38.6%, p < 0.01). North Indian patients had higher median National Institute of Health stroke scale scores (10 vs. 9, p < 0.01), more frequent large-artery atherosclerosis mechanism (34% vs. 25.6%, p < 0.001), intravenous thrombolysis (14.0% vs. 6.1%, p < 0.001), and lower rates of pneumonia (10.5% vs. 15.1%, p = 0.02). The three-month outcome (modified Rankin Scale score 0-2, 45.8% vs. 50.3%, p = 0.08) did not differ; however, North Indian patients had higher 90-day mortality (23.5% vs. 13.5%, p < 0.0001). CONCLUSIONS: The substantial regional differences in stroke risk factors and mechanisms may be partly explained by factors such as differing dietary habits and lifestyle, which can be addressed at a national level. Differences in acute and inpatient stroke care suggest a need for better adoption of national stroke management guidelines.