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OBJECTIVE: To observe the effect of overground gait training with 'Mobility Assisted Robotic System-MARS' on gait parameters in patients with stroke. PATIENTS & METHODS: This prospective pre-post study was conducted in a tertiary teaching research hospital with 29 adult stroke patients, with age up to 65 years. Patients fulfilling the inclusion criteria were divided in 2 groups based on the duration of stroke (≤ 6 months-sub-acute & > 6 months-chronic stroke) and provided overground gait training with MARS robot for 12 sessions (1 h/session) over a period of 2-3 weeks. Primary outcome measures were; 10-Meter walk test-10MWT, 6-min' walk test-6MWT and Timed up & Go-TUG tests. Secondary outcome measures were Functional Ambulation Category-FAC, Modified Rankin Scale-MRS and Scandinavian Stroke Scale-SSS. RESULTS: No adverse events were reported. Twenty-five patients who were able to perform 10-MWT at the beginning of study were included in the final analysis with 12 in sub-acute and 13 in chronic stroke group. All primary and secondary outcome measures showed significant improvement in gait parameters at the end of the training (p < 0.05) barring 10-Meter walk test in sub-acute stroke group (p = 0.255). Chronic stroke group showed significant minimum clinically important difference-MCID difference in endurance (6MWT) at the end of the training and both groups showed better 'minimal detectable change-MDC' in balance (TUG) at the end of the training. CONCLUSIONS: Patients in both the groups showed significant improvement in walking speed, endurance, balance and independence at the end of the training with overground gait training with MARS Robot. CLINICAL TRIAL REGISTRY: National Clinical Trial Registry of India (CTRI/2021/08/035695,16/08/2021).
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Trastornos Neurológicos de la Marcha , Procedimientos Quirúrgicos Robotizados , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Adulto , Humanos , Terapia por Ejercicio , Marcha , Estudios Prospectivos , Accidente Cerebrovascular/complicaciones , Resultado del Tratamiento , CaminataRESUMEN
BACKGROUND: Recently, TANK binding kinase 1 (TBK1) mutation has been reported as a causative gene for overlap frontotemporal dementia (FTD)-amyotrophic lateral sclerosis (ALS) syndrome. However, there are no reports from families of South Asian ethnicity. OBJECTIVE: To report a case study of a family with the proband having overlap FTD-ALS syndrome caused by a novel TBK1 variant. MATERIALS AND METHODS: Clinical, brain imaging, genetic analysis and laboratory data of the patient with FTD-ALS were performed. In addition, family-based segregation analysis of identified novel variants was also done. RESULTS: This study pertains to genetic analysis in 11 members in a family with only one member affected with overlap FTD-ALS syndrome. The whole-exome sequencing analysis in the symptomatic member showed a novel loss-of-function (LoF) variant c.1810G>T(p.E604X) in the TBK1 gene. Neuroimaging showed a pattern of asymmetric frontotemporal atrophy and hypometabolism. Segregation analysis of the variation demonstrated its presence in several family members, although none of the other members was symptomatic. Further, we observed another missense variation in the NEFH gene (p.Pro683Leu) which was seen in the symptomatic and two asymptomatic family members, the pathogenicity of which is unclear. CONCLUSION: This is the first study of a rare novel TBK1 variant associated with FTD-ALS from India. Asymptomatic family members with the variant have important clinical implications and necessitate the genetic evaluation and long-term follow-up of family members of patients detected with TBK1 mutations. Therefore, although infrequent, genetic screening for the TBK1 gene should be considered when encountering overlap FTD syndromes.
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Esclerosis Amiotrófica Lateral , Demencia Frontotemporal , Proteínas Serina-Treonina Quinasas , Esclerosis Amiotrófica Lateral/diagnóstico , Demencia Frontotemporal/diagnóstico por imagen , Demencia Frontotemporal/genética , Pruebas Genéticas , Humanos , Mutación , Proteínas Serina-Treonina Quinasas/genéticaRESUMEN
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.
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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.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Demencia , Enfermedad de Alzheimer/psicología , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/psicología , Estudios Transversales , Demencia/complicaciones , Demencia/diagnóstico , Demencia/psicología , Humanos , Pruebas de Estado Mental y Demencia , Pruebas NeuropsicológicasRESUMEN
OBJECTIVE: In the background of an emerging role for immune dysregulation in neurodegenerative dementias, this study aimed to investigate the relationship between systemic autoimmunity and dementia. The objective was to study the frequency and profile of disease-specific autoantibodies in Alzheimer's dementia (AD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB). METHODS: Immunological testing was performed in a large cohort of neurodegenerative dementia diagnosed based on standard clinical and imaging criteria. Patients were evaluated for the presence of autoantibodies specific for systemic autoimmune diseases that included anti-extractable nuclear antibody profile, rheumatoid factor antibody (RA), perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA), and cytoplasmic anti-neutrophil cytoplasmic antibody (c-ANCA) in serum. RESULTS: Of 174 patients with degenerative dementia (FTD = 114, AD = 53, and DLB = 7) evaluated with immunological testing, 18.9% (n = 33) were seropositive for autoantibodies. The common antibodies detected were anti-Scl-70 (25%), anti-Ro-52 (18.7%), anti-nRNP-Sm (12.5%), and anti-CENP-B (9.3%). There were no significant systemic complaints in the majority of patients. A wider range of antibodies were positive in FTD compared to AD and DLB. While no difference was observed in the mean age, sex, or duration of illness between seropositive and negative patients, family history of dementia was more frequent among seronegative patients. CONCLUSION: Our findings indicate an emerging role for immune dysregulation in patients with classical neurodegenerative dementias, especially those with FTD. These autoantibodies could play a role in immune degradation of protein aggregates that characterize neurodegeneration. Study findings emphasize the need to explore the complex relationship between systemic autoimmunity and neurodegenerative dementia.
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Enfermedad de Alzheimer , Demencia Frontotemporal , Enfermedad por Cuerpos de Lewy , Enfermedad de Pick , Enfermedad de Alzheimer/diagnóstico , Autoanticuerpos , Demencia Frontotemporal/diagnóstico , HumanosRESUMEN
BACKGROUND/AIMS: In a linguistically diverse country such as India, challenges remain with regard to diagnosis of early cognitive decline among the elderly, with no prior attempts made to simultaneously validate a comprehensive battery of tests across domains in multiple languages. This study aimed to determine the utility of the Indian Council of Medical Research-Neurocognitive Tool Box (ICMR-NCTB) in the diagnosis of mild cognitive impairment (MCI) and its vascular subtype (VaMCI) in 5 Indian languages. METHODS: Literate subjects from 5 centers across the country were recruited using a uniform process, and all subjects were classified based on clinical evaluations and a gold standard test protocol into normal cognition, MCI, and VaMCI. Following adaptation and harmonization of the ICMR-NCTB across 5 different Indian languages into a composite Z score, its test performance against standards, including sensitivity and specificity of the instrument as well as of its subcomponents in diagnosis of MCI, was evaluated in age and education unmatched and matched groups. RESULTS: Variability in sensitivity-specificity estimates was noted between languages when a total of 991 controls and 205 patients with MCI (157 MCI and 48 VaMCI) were compared due to a significant impact of age, education, and language. Data from a total of 506 controls, 144 patients with MCI, and 46 patients with VaMCI who were age- and education-matched were compared. Post hoc analysis after correction for multiple comparisons revealed better performance in controls relative to all-cause MCI. An optimum composite Z-score of -0.541 achieved a sensitivity of 81.1% and a specificity of 88.8% for diagnosis of all-cause MCI, with a high specificity for diagnosis of VaMCI. Using combinations of multiple-domain 2 test subcomponents retained a sensitivity and specificity of >80% for diagnosis of MCI. CONCLUSIONS: The ICMR-NCTB is a "first of its kind" approach at harmonizing neuropsychological tests across 5 Indian languages for the diagnosis of MCI due to vascular and other etiologies. Utilizing multiple-domain subcomponents also retains the validity of this instrument, making it a valuable tool in MCI research in multilingual settings.
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Disfunción Cognitiva , Diversidad Cultural , Demencia Vascular , Lenguaje , Pruebas Neuropsicológicas/normas , Anciano , Cognición , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/psicología , Demencia Vascular/diagnóstico , Demencia Vascular/epidemiología , Escolaridad , Femenino , Humanos , India/epidemiología , Masculino , Reproducibilidad de los Resultados , Proyectos de Investigación , Sensibilidad y EspecificidadRESUMEN
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.
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Disfunción Cognitiva/diagnóstico , Diversidad Cultural , Demencia/diagnóstico , Pruebas Neuropsicológicas/normas , Guías de Práctica Clínica como Asunto/normas , Psicometría/normas , Demencia/etiología , Humanos , India , Enfermedades Neurodegenerativas/complicaciones , Psicometría/instrumentación , Psicometría/métodos , Accidente Cerebrovascular/complicaciones , TraducciónRESUMEN
BACKGROUND: Increasing evidence suggests that life course factors such as education and bilingualism may have a protective role against dementia due to Alzheimer disease. This study aimed to compare the effects of education and bilingualism on the onset of cognitive decline at the stage of mild cognitive impairment (MCI). METHODS: A total of 115 patients with MCI evaluated in a specialty memory clinic in Hyderabad, India, formed the cohort. MCI was diagnosed according to Petersen's criteria following clinical evaluation and brain imaging. Age at onset of MCI was compared between bilinguals and monolinguals, and across subjects with high and low levels of education, adjusting for possible confounding variables. RESULTS: The bilingual MCI patients were found to have a clinical onset of cognitive complaints 7.4 years later than monolinguals (65.2 vs. 58.1 years; p = 0.004), while years of education was not associated with delayed onset (1-10 years of education, 59.1 years; 11-15 years of education, 62.6 years; >15 years of education, 62.2 years; p = 0.426). CONCLUSION: The effect of bilingualism is protective against cognitive decline, and lies along a continuum from normal to pathological states. In comparison, the role of years of education is less robust.
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Disfunción Cognitiva/psicología , Escolaridad , Multilingüismo , Adulto , Edad de Inicio , Anciano , Disfunción Cognitiva/epidemiología , Estudios de Cohortes , Femenino , Humanos , India/epidemiología , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Factores de Riesgo , Factores SocioeconómicosRESUMEN
Subcutaneous unfractionated heparin (SCUFH) has been proved effective in puerperal cerebral venous thrombosis (CVT), but its efficacy in the more serious form of the disease such as deep CVT patients (DCVT) unreported. We describe the outcomes of 37 (isolated:combined: 11:26) patients of DCVT diagnosed by MRI, treated with SCUFH in a tertiary care stroke unit. It was a prospective observational cohort study using 5000 U of SCUFH every 6 hourly for 10 days with oral Acenocoumarol started on day 7, with monitoring. The outcome was assessed by modified Rankin scale (mRS), National Institute of Health Stroke Scale (NIHSS) and Barthel's activities of daily life (BADL) at 3 months. The mean age of the cohort was 27.9 ± 9.7 years, females (n = 24) outnumbering the males (n = 13). Mean duration of symptoms being 10.2 ± 15.9 days. MRI showed vein of Galen and straight sinus involvement in 36 (97.3%) patients, with sparing of the basal vein of Rosenthal in 28 (75%). Thalamus 27 (73%) basal ganglia 21 (56.7%) were commonly involved areas with hemorrhagic lesions in 18 (48.6%) patients. The median NIHSS score at presentation was 11 (1-21). Mean duration of SCUFH treatment was 9.3 ± 1.3 days and the mean aPTT on day 7 was 49.3 ± 9.8 s (control 32-39 s), mean PT INR on day 13 was 1.5 ± 0.45. All the patients improved with no mortality in the study group. At 3 months, good functional outcome (mRS: 0-2) was observed in 94.6% (n = 35) of patients. Two patients had mRS-3. The median mRS (3{1-5} to 0{0-3}) and BADL (8{0-20} to 20{8-20}) improved at 3 months. Complications seen were thrombocytopenia-1, infection-6 and deep vein thrombosis of leg-4. Our preliminary data suggests that SCUFH is safe, effective treatment option in patients with DCVT in a stroke unit with minimal monitoring.
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Heparina/uso terapéutico , Trombosis Intracraneal/tratamiento farmacológico , Trombosis de la Vena/tratamiento farmacológico , Acenocumarol/administración & dosificación , Adolescente , Adulto , Estudios de Cohortes , Monitoreo de Drogas , Femenino , Heparina/administración & dosificación , Heparina/efectos adversos , Humanos , Inyecciones Subcutáneas , Trombosis Intracraneal/complicaciones , Imagen por Resonancia Magnética , Masculino , Tiempo de Tromboplastina Parcial , Estudios Prospectivos , Resultado del Tratamiento , Trombosis de la Vena/complicaciones , Adulto JovenRESUMEN
Acute toxic leukoencephalopathy and serotonin syndrome are rare neurological complications associated with various drugs and toxins, some of which overlap. However, the co-occurrence of these conditions is poorly documented. We present the case of a 14-year-old boy who suddenly developed altered consciousness and autonomic dysfunction after consuming excessive quantities of cough remedies containing dextromethorphan, chlorphenamine, dichlorobenzyl alcohol, and amylmetacreson. Magnetic resonance imaging of the brain revealed distinct white matter lesions. With supportive care, the patient rapidly improved, and the magnetic resonance imaging abnormalities disappeared. The swift resolution, typical magnetic resonance imaging findings, and a history of exposure to drugs affecting the central nervous system's serotonergic system suggested concurrent acute toxic leukoencephalopathy and serotonin syndrome. The components of cough medications can be hazardous in overdose due to their potential to enhance serotonin toxicity and cause direct or indirect central nervous system white matter damage. Early recognition and appropriate treatment are essential for recovery.
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Sobredosis de Droga , Leucoencefalopatías , Síndrome de la Serotonina , Masculino , Humanos , Adolescente , Síndrome de la Serotonina/inducido químicamente , Síndrome de la Serotonina/diagnóstico , Síndrome de la Serotonina/patología , Sobredosis de Droga/complicaciones , Sobredosis de Droga/patología , Leucoencefalopatías/diagnóstico , Leucoencefalopatías/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Imagen por Resonancia Magnética , TosRESUMEN
Background: Idiopathic intracranial hypertension (IIH) typically manifests with headache, accompanied by papilledema and visual loss, and has a higher prevalence in females. In recent years, ocular sonography, particularly, measurement of optic nerve sheath diameter (ONSD), is being investigated for diagnosis of IIH. Methods: A total of 35 patients over the age of 18 years, fulfilling the modified Dandy's criteria for diagnosis of IIH were included. Patients underwent assessment with magnetic resonance imaging, lumbar puncture, and ocular sonography to measure ONSD and ocular arterial indices. Results: The mean ONSD values (in centimeters) in the right eye of patients with IIH was 0.57 ± 0.13, while it was 0.48 ± 0.03 in controls. In the left eye, the mean ONSD value (cm) was 0.59 ± 0.13 in patients with IIH and 0.48 ± 0.03 in controls. ONSD was significantly higher in cases compared to controls (P < 0.001, Welch test). Pulsatility index of the central retinal artery was significantly higher in cases compared to controls (P < 0.001, Welch test). Resistance index of the ophthalmic artery was statistically significant (P < 0.005, Welch test). Receiver operating characteristic curve analysis revealed a cutoff value of 5.1 mm on the right side and 5 mm on the left side had a sensitivity and specificity of more than 80% for IIH diagnosis. Conclusion: Our study provides insights into the utility of optic nerve sheath measurements and arterial indices in the diagnosis of IIH in a South Indian cohort. Further research is needed to fully understand the longitudinal relationship of these parameters and treatment outcomes in IIH.
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OBJECTIVE: Motor imagery-based brain-computer interface (MI-BCI) is a promising novel mode of stroke rehabilitation. The current study aims to investigate the feasibility of MI-BCI in upper limb rehabilitation of chronic stroke survivors and also to study the early event-related desynchronization after MI-BCI intervention. METHODS: Changes in the characteristics of sensorimotor rhythm modulations in response to a short brain-computer interface (BCI) intervention for upper limb rehabilitation of stroke-disabled hand and normal hand were examined. The participants were trained to modulate their brain rhythms through motor imagery or execution during calibration, and they played a virtual marble game during the feedback session, where the movement of the marble was controlled by their sensorimotor rhythm. RESULTS: Ipsilesional and contralesional activities were observed in the brain during the upper limb rehabilitation using BCI intervention. All the participants were able to successfully control the position of the virtual marble using their sensorimotor rhythm. CONCLUSIONS: The preliminary results support the feasibility of BCI in upper limb rehabilitation and unveil the capability of MI-BCI as a promising medical intervention. This study provides a strong platform for clinicians to build upon new strategies for stroke rehabilitation by integrating MI-BCI with various therapeutic options to induce neural plasticity and recovery.
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Background: Deep cerebral venous thrombosis (DCVT) can have long-term functional and cognitive sequelae. Although literature exists on cognitive impairment after arterial stroke, cognitive sequelae after cerebral venous thrombosis (CVT) are much less studied. Methods: Clinical records of 29 patients diagnosed with DCVT were reviewed. The Modified Telephonic Interview for Cognitive Status (TICS-M) was adapted and validated in the regional language (Kannada) and applied to 18 patients with DCVT, at a mean follow-up duration of 5.32 years. Screening for depression was done via telephonic Patient Health Questionnaire-9 (PHQ-9)-Kannada version, and functional status was screened by applying the modified Rankin Scale (mRS). Results: DCVT had a mortality rate of 10.34% due to acute complications. mRS scores of 0-1 were achieved at follow-up in all patients who survived. Receiver operating characteristic (ROC) analysis revealed a cutoff of ≤44.5 (maximum score of 49) for the diagnosis of cognitive impairment via TICS-M (Kannada version) in DCVT patients. Evidence of cognitive dysfunction was seen in eight patients (42.10%), and three patients (16.66%) had evidence of depression. Conclusions: Survivors of acute DCVT can potentially have long-term cognitive sequelae. Screening for cognitive dysfunction, depression, and functional status can be effectively done using telephonically applied scales that are adapted to the local language. Neuropsychological evaluation and early cognitive rehabilitation can be initiated for patients in whom deficits are identified on cognitive screening.
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Introduction: Microglia exert a crucial role in homeostasis of white matter integrity, and several studies highlight the role of microglial dysfunctions in neurodegeneration. Primary microgliopathy is a disorder where the pathogenic abnormality of the microglia causes white matter disorder and leads to a neuropsychiatric disease. Triggering receptor expressed on myeloid cells (TREM2), TYRO protein tyrosine kinase binding protein (TYROBP) and colony-stimulating factor 1 receptor (CSF1R) are genes implicated in primary microgliopathy. The clinical manifestations of primary microgliopathy are myriad ranging from neuropsychiatric syndrome, motor disability, gait dysfunction, ataxia, pure dementia, frontotemporal dementia (FTD), Alzheimer's dementia (AD), and so on. It becomes imperative to establish the diagnosis of microgliopathy masquerading as degenerative dementia, especially with promising therapies on horizon for the same. We aimed to describe a case series of subjects with dementia harbouring novel genes of primary microgliopathy, along with their clinical, neuropsychological, cognitive profile and radiological patterns. Methods: The prospective study was conducted in a university referral hospital in South India, as a part of an ongoing clinico-genetic research on dementia subjects, and was approved by the Institutional Ethics Committee. All patients underwent detailed assessment including sociodemographic profile, clinical and cognitive assessment, pedigree analysis and comprehensive neurological examination. Subjects consenting for blood sampling underwent genetic testing by whole-exome sequencing (WES). Results: A total of 100 patients with dementia underwent genetic analysis using WES and three pathogenic variants, one each of TREM2, TYROBP, and CSF1R and two variants of uncertain significance in CSF1R were identified as cause of primary microgliopathy. TREM2 and TYROBP presented as frontotemporal syndrome whereas CSF1R presented as frontotemporal syndrome and as AD. Conclusion: WES has widened the spectrum of underlying neuropathology of degenerative dementias, and diagnosing primary microglial dysfunction with emerging therapeutic options is of paramount importance. The cases of primary microgliopathy due to novel mutations in TREM2, TYROBP, and CSF1R with the phenotype of degenerative dementia are being first time reported from Indian cohort. Our study enriches the spectrum of genetic variants implicated in degenerative dementia and provides the basis for exploring complex molecular mechanisms like microglial dysfunction, as underlying cause for neurodegeneration.
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Aberrant alterations in any of the two dimensions of consciousness, namely awareness and arousal, can lead to the emergence of disorders of consciousness (DOC). The development of DOC may arise from more severe or targeted lesions in the brain, resulting in widespread functional abnormalities. However, when it comes to classifying patients with disorders of consciousness, particularly utilizing resting-state electroencephalogram (EEG) signals through machine learning methods, several challenges surface. The non-stationarity and intricacy of EEG data present obstacles in understanding neuronal activities and achieving precise classification. To address these challenges, this study proposes variational mode decomposition (VMD) of EEG before feature extraction along with machine learning models. By decomposing preprocessed EEG signals into specified modes using VMD, features such as sample entropy, spectral entropy, kurtosis, and skewness are extracted across these modes. The study compares the performance of the features extracted from VMD-based approach with the frequency band-based approach and also the approach with features extracted from raw-EEG. The classification process involves binary classification between unresponsive wakefulness syndrome (UWS) and the minimally conscious state (MCS), as well as multi-class classification (coma vs. UWS vs. MCS). Kruskal-Wallis test was applied to determine the statistical significance of the features and features with a significance of p < 0.05 were chosen for a second round of classification experiments. Results indicate that the VMD-based features outperform the features of other two approaches, with the ensemble bagged tree (EBT) achieving the highest accuracy of 80.5% for multi-class classification (the best in the literature) and 86.7% for binary classification. This approach underscores the potential of integrating advanced signal processing techniques and machine learning in improving the classification of patients with disorders of consciousness, thereby enhancing patient care and facilitating informed treatment decision-making.
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Diagnosis and treatment of cerebral venous sinus thrombosis (CVT) associated with subdural hematoma (SDH) is challenging with an increased risk of rebleeding on using anticoagulation. There are no guidelines at present due to its rare presentation. In this report we describe three patients who presented with non-traumatic SDH and CVT over the last 3 years. Clinical assessment, investigations including neuroimaging, and management were reviewed both at time of admission and follow-up. These patients presented with varied CVT syndromes -isolated raised intracranial pressure (ICP), focal and diffuse encephalopathy. Neuroimaging helped in diagnosing CVT and SDH. Cases 1 and 3 had SDH alone, while case 2 had SDH along with intraparenchymal hemorrhage. Management of these patients was tailored individually as per mechanism of CVT. Case 1 was clinically stable, however, she had rebleeding after starting anticoagulation, requiring its discontinuation. Cases 2 and 3 underwent immediate neurosurgical intervention in view of deteriorated sensorium. Although CVT manifesting as SDH is rare, clinicians should have a high index of suspicion to accurately diagnose and manage these challenging cases. The decision regarding use of anticoagulation and apt time for neurosurgical intervention needs to be individualized depending on patients condition and response to treatment.
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Background: Due to effective treatment of middle ear infections there is a change in etiologies causing lateral sinus thrombosis (LST) and outcome. There is a paucity of literature describing homogenous group of patients with nonseptic LST (NS-LST). Objective: To describe the clinical profile, risk factors, outcome of patients of NS-LST seen at a single center from South India. Methods and Materials: Prospective, observational study of 100 patients of NS-LST patients, diagnosed by magnetic resonance imaging (MRI) seen at the stroke unit. Results: During 2 years, 100 patients of NS-LST (isolated: combined: 27:73) (male: female: 44:56), mean age: 31.45 ± 11.13 years, were seen. Subacute presentation (74%) with headache, seizures, focal deficits, and features of raised intracranial pressure were presenting features. Hyperhomocysteinemia (61%), anemia (57%), postpartum state (41%), OCP use (37%), and low VitB12 (32%) were commonly seen risk factors. Imaging with MRI compared withcomputerized tomography (CT) had better diagnostic sensitivity (100% vs. 67%), detection of parenchymal (81% vs. 67%)/hemorrhagic (79% vs. 74%) lesions, and cortical vein thrombosis (31% vs. 15.46%). Treatment with anticoagulation and supportive therapy resulted in good outcome (mRS (0-2)) at 3 months in 81%.There were four deaths, all during admission (one - isolated, three - combined) and 11 patients underwent decompressive surgery. Patients with low GCS level of sensoriumat admission, hemiparesis, combined LST, cerebellar involvement, and decompressive craniectomy had a poor outcome. Conclusion: This single-center large cohort study of NS-LST patients brings out the clinical features, risk factors (peculiar to developing countries), and the superiority of MRI in the diagnosis. Majority of patients have good outcome, with low mortality with 10% requiring decompressive surgery.