Carotid Health in Patients with Cerebral Venous Thrombosis.

Background: Cerebral venous thrombosis (CVT) is an uncommon cause of stroke and shares common risk factors with arterial strokes such as hyperhomocysteinemia, tobacco, alcohol, drugs, and hypercoagulable state. These risk factors can alter both arterial and venous health leading to the occurrence of atherosclerosis in CVT patients. Aims: To evaluate carotid hemodynamics in CVT patients. Settings and Design: Prospective hospital-based case-control study. Methods: This study included 50 consecutive CVT patients and 50 healthy controls. The demographic data, vascular risk factors, clinical data, biochemical, and radiological parameters were recorded. Carotid sonography was performed in CVT patients within the first 24 h of admission. Statistical Analysis: MedCalc 17. Results: The age of the patients was 35.04 ± 9.48 years and the controls 38.88 ± 10.41 years with male preponderance in both groups. Risk factors for atherosclerosis among patients included hyperhomocysteinemia (40 patients), diabetes mellitus (4 patients), hypertension (9 patients), alcohol (17 patients), and tobacco (21 patients). Eight patients had abnormal carotid sonography. Six had nonflow-limiting plaques, one had carotid occlusion, two had increased intimal-medial thickness, and one had increased peak systolic velocity. Among the controls, three subjects had nonflow-limiting plaques. There was no difference in carotid hemodynamic parameters between controls and patients; and those with normal and elevated homocysteine. Conclusion: This is the first study to our knowledge looking at carotid health in venous strokes. The relative risk for carotid atherosclerosis in CVT patients is higher and requires long-term follow-up for the initiation of preventive measures.

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.

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.

INSTRuCT: Protocol, Infrastructure, and Governance.

Background and Purpose: Very few large scale multicentric stroke clinical trials have been done in India. The Indian Council of Medical Research funded INSTRuCT (Indian Stroke Clinical Trial Network) as a task force project with the objectives to establish a state-of-the-art stroke clinical trial network and to conduct pharmacological and nonpharmacological stroke clinical trials relevant to the nation and globally. The purpose of the article is to enumerate the structure of multicentric stroke network, with emphasis on its scope, challenges and expectations in India. Methods: Multiple expert group meetings were conducted by Indian Council of Medical Research to understand the scope of network to perform stroke clinical trials in the country. Established stroke centers with annual volume of 200 patients with stroke with prior experience of conducting clinical trials were included. Central coordinating center, standard operating procedures, data and safety monitoring board were formed. Discussion: In first phase, 2 trials were initiated namely, SPRINT (Secondary Prevention by Structured Semi-Interactive Stroke Prevention Package in India) and Ayurveda treatment in the rehabilitation of patients with ischemic stroke in India (RESTORE [Rehabilitation of Ischemic stroke Patients in India: A Randomized controlled trial]). In second phase, 4 trials have been approved. SPRINT trial was the first to be initiated. SPRINT trial randomized first patient on April 28, 2018; recruited 3048 patients with an average of 128.5 per month so far. The first follow-up was completed on May 27, 2019. RESTORE trial randomized first patient on May 22, 2019; recruited 49 patients with an average of 3.7 per month so far. The first follow-up was completed on August 30, 2019. Conclusions: In next 5 years, INSTRuCT will be able to complete high-quality large scale stroke trials which are relevant globally. REGISTRATION: URL: http://www.ctri.nic.in/; Unique Identifier: CTRI/2017/05/008507.

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.

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.

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.

Prospective Hospital-Based Clinical and Electrophysiological Evaluation of Acute Organophosphate Poisoning.

INTRODUCTION: Acute organophosphate (OP) poisoning is one of the most common poisoning causing significant morbidity and mortality in developing countries. Acute cholinergic manifestations predominate with many patients requiring intensive care management and ventilator support. Nerve conduction studies including repetitive nerve stimulation can evaluate the altered neuromuscular transmission and peripheral nerve function by OPs. OBJECTIVE: To evaluate the electrophysiological abnormalities in patients with acute OP poisoning and correlate with clinical status. MATERIALS AND METHODS: Patients with acute OP poisoning admitted from August 2016 to August 2017 were prospectively studied. Nerve conduction studies including phrenic nerve conduction were performed within 24 h of admission. Repetitive nerve stimulation was performed at 3 and 30 Hz. Nerve conduction findings were compared with data from age-matched healthy controls. RESULTS: Thirty patients were included (18 men and 12 women) in the study. Their age ranged from 16 to 47 years (30 ± 9.2). The first assessment revealed a mild reduction of compound muscle action potential (CMAP) amplitude and reduced F-wave persistence. Eleven patients had repetitive CMAPs suggesting cholinergic excess. Seven among the 11 patients requiring mechanical ventilation had decrement-increment response with 30 Hz stimulation and reduced diaphragmatic CMAP amplitude (P = 0.02). CONCLUSION: The presence of repetitive CMAPs, decrement-increment response to tetanic stimulation and reduced diaphragmatic CMAP amplitude in OP poisoning patients correlate with neuromuscular paralysis and need for mechanical ventilation.

Hospital-based Retrospective Study of Cryptococcal Meningitis in a Large Cohort from India.

BACKGROUND: Cryptococcal meningitis is an important and a fatal neuroinfection. Early diagnosis and treatment is of utmost importance in reducing morbidity and mortality. MATERIALS AND METHODS: Data of patients with laboratory-confirmed cryptococcal meningitis seen in tertiary care hospital were reviewed. Details of demographic profile, clinical data, laboratory parameters, complications, and in-hospital mortality were studied. RESULTS: Among 97 patients with cryptococcal meningitis (79 men, 18 women), 88 were HIV-positive, two were diabetic, and seven were sporadic. Their age ranged from 23 to 67 years (39.16 ± 9.49). Additional pathogens for meningitis were identified in 24 patients. Headache was the most common symptom (91%) followed by fever (66%), vomiting (51%), altered sensorium (31%), and seizures (20%). Neurological deficits included cranial nerve palsies (28), motor deficits (11), sphincter disturbances (5), and sensory involvement in four patients. Complications included renal dysfunction (20%), dyselectrolytemia (20%), seizures (16%), hypersensitivity (7%), and hepatic dysfunction (5%). Favorable outcome was seen in 72 patients, 13 remained unchanged, and 12 died. Rapid clinical progression, low cerebrospinal fluid (CSF) cell count and protein were associated with higher mortality. CSF cell count and protein were lower in patients who had isolated cryptococcal meningitis compared to those with additional pathogen. Mean sugar levels were higher and duration of illness was shorter in HIV-negative individuals. CONCLUSION: Cryptococcal meningitis is common in patients with AIDS. Effective and early antifungal treatment carries a good prognosis. On rapid evolution of the disease, decreased CSF cell count and protein heralds poor prognosis and warrants initiation of early specific treatment.

Intact thumb reflex in areflexic Guillain Barré syndrome: A novel phenomenon.

INTRODUCTION: Areflexia is one of the cardinal clinical features for the diagnosis of Guillain Barré syndrome. However, some patients may have sluggish proximal muscle stretch reflexes. Presence of thumb reflex, a distal stretch muscle reflex has not been documented in Guillain Barré syndrome. MATERIALS AND METHODS: We prospectively evaluated thumb reflex in Guillain Barré syndrome patients and age matched controls from April to September 2013. RESULTS: There were 31 patients with Guillain Barré syndrome in whom thumb reflex could be elicited in all (24 brisk, 7 sluggish), whereas all the other muscle stretch reflexes were absent in 29 patients at presentation and the remaining two had sluggish biceps and quadriceps reflexes (P = 0.001). Serial examination revealed gradual diminution of the thumb reflex (P < 0.001). Rapid progression of weakness was associated with early loss of the thumb reflex. CONCLUSION: Thumb reflex, a distal stretch reflex is preserved in the early phase of Guillain Barré syndrome.

Electromyographic and histological features of postpartum hypernatremic rhabdomyolysis.

INTRODUCTION: Rhabdomyolysis results from many causes including hypernatremia. Postpartum hypernatremia with osmotic cerebral demyelination is a rare cause of reversible rhabdomyolysis. Electromyographic studies in postpartum hypernatremia have not been reported. MATERIALS AND METHODS: Electromyography (EMG) was performed in five women with postpartum hypernatremia and muscle biopsy was performed in one of them. RESULTS: Among the five women presenting with postpartum hypernatremia associated with marked elevation of serum creatine kinase, four had quadriparesis. All had varying degrees of encephalopathy at admission and recovered without residual deficits after gradual correction of hypernatremia. Needle EMG revealed fibrillations with positive sharp waves in five patients and myotonic discharges in three patients. Serial EMG in one patient revealed the occurrence of transient fibrillations, positive sharp waves and myotonic discharges. Muscle biopsy revealed extensive rhabdomyolysis in one patient. CONCLUSION: EMG in hypernatremic rhabdomyolysis revealed spontaneous activity including fibrillations, positive sharp waves and myotonic discharges along with myopathic potentials. Electromyographic findings depend on the interval from the onset and the degree of rhabdomyolysis.

Bethlem myopathy: An autosomal dominant myopathy with flexion contractures, keloids, and follicular hyperkeratosis.

Bethlem myopathy and Ullrich congenital muscular dystrophy form a spectrum of collagenopathies caused by genetic mutations encoding for any of the three subunits of collagen VI. Bethlem phenotype is relatively benign and is characterized by proximal dominant myopathy, keloids, contractures, distal hyperextensibility, and follicular hyperkeratosis. Three patients from a single family were diagnosed to have Bethlem myopathy based on European Neuromuscular Centre Bethlem Consortium criteria. Affected father and his both sons had slowly progressive proximal dominant weakness and recurrent falls from the first decade. Both children aged 18 and 20 years were ambulant at presentation. All had flexion contractures, keloids, and follicular hyperkeratosis without muscle hypertrophy. Creatinine kinase was mildly elevated and electromyography revealed myopathic features. Muscle imaging revealed severe involvement of glutei and vasti with "central shadow" in rectus femoris. Muscle biopsy in the father showed dystrophic changes with normal immmunostaining for collagen VI, sarcoglycans, and dysferlin.

Uncommon dyselectrolytemia complicating Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) and hypokalemic paralysis are common causes of acute flaccid quadriparesis and specific therapeutic interventions differ. Simultaneous occurrence of severe hypokalemia in patients with GBS at the time of presentation can cause diagnostic and therapeutic dilemma. Presence of hypomagnesemia with hypokalemia in patients with GBS can be perplexing and pose further challenges. Evaluation for preexisting inherited or other associated metabolic disturbances is needed in the presence of such complex dyselectrolytemia. We report the rare association of GBS with severe hypokalemia and hypomagnesemia in a 41-year-old male presenting with acute flaccid quadriparesis and the therapeutic challenges faced.

Familial Guillain-Barré syndrome: First Indian report.

Guillain-Barré syndrome (GBS) is the commonest acute immune-mediated peripheral neuropathy. Specific human leukocyte antigen types have been found in patients with axonal and demyelinating subtypes of GBS suggesting genetic susceptibility in the generation of GBS. However, familial occurrence of GBS is rare and 42 patients from 20 families have been reported. Majority of them are from European countries and two families have been documented from Asian countries, while none have been reported from India. Electrophysiological characterization in familial GBS has been limited. We report the clinical and detailed electrophysiological findings in two affected brothers with familial GBS from India who had GBS five years apart. Both of them had mixed axonal and demyelinating features in nerve conductions and had complete clinical recovery. Our report documents the first Indian familial occurrence of GBS. Detailed genetic and epidemiological studies are required to find the true prevalence of familial GBS.