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At present, there is no internationally accepted set of core outcomes or measurement methods for epilepsy clinical practice. Therefore, the International Consortium for Health Outcomes Measurement (ICHOM) convened an international working group of experts in epilepsy, people with epilepsy and their representatives to develop minimum sets of standardized outcomes and outcomes measurement methods for clinical practice that support patient-clinician decision-making and quality improvement. Consensus methods identified 20 core outcomes. Measurement tools were recommended based on their evidence of strong clinical measurement properties, feasibility, and cross-cultural applicability. The essential outcomes included many non-seizure outcomes: anxiety, depression, suicidality, memory and attention, sleep quality, functional status, and the social impact of epilepsy. The proposed set will facilitate the implementation of the use of patient-centered outcomes in daily practice, ensuring holistic care. They also encourage harmonization of outcome measurement, and if widely implemented should reduce the heterogeneity of outcome measurement, accelerate comparative research, and facilitate quality improvement efforts.
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Consenso , Epilepsia , Avaliação de Resultados em Cuidados de Saúde , Humanos , Epilepsia/diagnóstico , Epilepsia/terapia , Avaliação de Resultados em Cuidados de Saúde/normas , Avaliação de Resultados em Cuidados de Saúde/métodos , AdultoRESUMO
At present, there is no internationally accepted set of core outcomes or measurement methods for epilepsy clinical practice. The International Consortium for Health Outcomes Measurement (ICHOM) convened an international working group of experts in epilepsy, people with epilepsy, and their representatives to develop minimum sets of standardized outcomes and outcome measurement methods for clinical practice. Using modified Delphi consensus methods with consecutive rounds of online voting over 12 months, a core set of outcomes and corresponding measurement tool packages to capture the outcomes were identified for infants, children, and adolescents with epilepsy. Consensus methods identified 20 core outcomes. In addition to the outcomes identified for the ICHOM Epilepsy adult standard set, behavioral, motor, and cognitive/language development outcomes were voted as essential for all infants and children with epilepsy. The proposed set of outcomes and measurement methods will facilitate the implementation of the use of patient-centered outcomes in daily practice.
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Consenso , Epilepsia , Avaliação de Resultados em Cuidados de Saúde , Humanos , Epilepsia/diagnóstico , Criança , Adolescente , Lactente , Avaliação de Resultados em Cuidados de Saúde/normas , Avaliação de Resultados em Cuidados de Saúde/métodos , Técnica Delphi , Pré-EscolarRESUMO
BACKGROUND: Tuberculous meningitis is a serious form of tuberculosis (TB) that affects the meninges that cover a person's brain and spinal cord. It is associated with high death rates and with disability in people who survive. Corticosteroids have been used as an adjunct to antituberculous drugs to treat people with tuberculous meningitis, but their role has been controversial. OBJECTIVES: To evaluate the effects of corticosteroids as an adjunct to antituberculous treatment on death and severe disability in people with tuberculous meningitis. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register up to the 18 March 2016; CENTRAL; MEDLINE; EMBASE; LILACS; and Current Controlled Trials. We also contacted researchers and organizations working in the field, and checked reference lists. SELECTION CRITERIA: Randomized controlled trials that compared corticosteroid plus antituberculous treatment with antituberculous treatment alone in people with clinically diagnosed tuberculous meningitis and included death or disability as outcome measures. DATA COLLECTION AND ANALYSIS: We independently assessed search results and methodological quality, and extracted data from the included trials. We analysed the data using risk ratios (RR) with 95% confidence intervals (CIs) and used a fixed-effect model. We performed an intention-to-treat analysis, where we included all participants randomized to treatment in the denominator. This analysis assumes that all participants who were lost to follow-up have good outcomes. We carried out a sensitivity analysis to explore the impact of the missing data. MAIN RESULTS: Nine trials that included 1337 participants (with 469 deaths) met the inclusion criteria.At follow-up from three to 18 months, steroids reduce deaths by almost one quarter (RR 0.75, 95% CI 0.65 to 0.87; nine trials, 1337 participants, high quality evidence). Disabling neurological deficit is not common in survivors, and steroids may have little or no effect on this outcome (RR 0.92, 95% CI 0.71 to 1.20; eight trials, 1314 participants, low quality evidence). There was no difference between groups in the incidence of adverse events, which included gastrointestinal bleeding, invasive bacterial infections, hyperglycaemia, and liver dysfunction.One trial followed up participants for five years. The effect on death was no longer apparent at this time-point (RR 0.93, 95% CI 0.78 to 1.12; one trial, 545 participants, moderate quality evidence); and there was no difference in disabling neurological deficit detected (RR 0.91, 95% CI 0.49 to 1.69; one trial, 545 participants, low quality evidence).One trial included human immunodeficiency virus (HIV)-positive people. The stratified analysis by HIV status in this trial showed no heterogeneity, with point estimates for death (RR 0.90, 95% CI 0.67 to 1.20; one trial, 98 participants) and disability (RR 1.23, 95% CI 0.08 to 19.07; one trial, 98 participants) similar to HIV-negative participants in the same trial. AUTHORS' CONCLUSIONS: Corticosteroids reduce mortality from tuberculous meningitis, at least in the short term.Corticosteroids may have no effect on the number of people who survive tuberculous meningitis with disabling neurological deficit, but this outcome is less common than death, and the CI for the relative effect includes possible harm. However, this small possible harm is unlikely to be quantitatively important when compared to the reduction in mortality.The number of HIV-positive people included in the review is small, so we are not sure if the benefits in terms of reduced mortality are preserved in this group of patients.
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Antituberculosos/uso terapêutico , Glucocorticoides/uso terapêutico , Tuberculose Meníngea/tratamento farmacológico , Adulto , Quimioterapia Adjuvante , Criança , Dexametasona/uso terapêutico , Humanos , Hidrocortisona/uso terapêutico , Análise de Intenção de Tratamento , Prednisolona/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Tuberculose Meníngea/mortalidadeRESUMO
Primary CNS Vasculitis (PCNSV) is a rare, diverse, and polymorphic CNS blood vessel inflammatory condition. Due to its rarity, clinical variability, heterogeneous imaging results, and lack of definitive laboratory markers, PCNSV diagnosis is challenging. This retrospective cohort analysis identified patients with histological diagnosis of PCNSV. Demographic data, clinical presentation, neuroimaging studies, and histopathologic findings were recorded. We enrolled 56 patients with a positive biopsy of CNS vasculitis. Most patients had cerebral hemisphere or brainstem symptoms. Most brain MRI lesions were bilateral, diffuse discrete to confluent white matter lesions. Frontal lobe lesions predominated, followed by inferior cerebellar lesions. Susceptibility-weighted imaging (SWI) hemorrhages in 96.4% (54/56) of patients, either solitary microhemorrhages or a combination of micro and macrohemorrhages. Contrast-enhanced T1-WIs revealed parenchymal enhancement in 96.3% (52/54 patients). The most prevalent pattern of enhancement observed was dot-linear (87%), followed by nodular (61.1%), perivascular (25.9%), and patchy (16.7%). Venulitis was found in 19 of 20 individuals in cerebral DSA. Hemorrhages in SWI and dot-linear enhancement pattern should be incorporated as MINOR diagnostic criteria to diagnose PCNSV accurately within an appropriate clinical context. Microhemorrhages in SWI and venulitis in DSA, should be regarded as a potential marker for PCNSV.
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Imageamento por Ressonância Magnética , Vasculite do Sistema Nervoso Central , Humanos , Estudos Retrospectivos , Estudos de Coortes , Vasculite do Sistema Nervoso Central/diagnóstico por imagem , Vasculite do Sistema Nervoso Central/patologia , HemorragiaRESUMO
PURPOSE: To test the applicability of the new International League Against Epilepsy (ILAE) 2010 classification for epilepsies and to compare it with the ILAE 1989 classification and the ILAE 2001 diagnostic scheme in developing countries with limited resources such as India. METHODS: Prospective data of 500 consecutive patients with epilepsy, presenting in neurology department of All India Institute of Medical Sciences, was collected from January 2011 to June 2012 and analyzed according to the three systems proposed by ILAE in 1989, 2001, and 2010. KEY FINDINGS: All 500 patients could be classified in the ILAE 1989 classification system, but only 413 in the ILAE 2001 diagnostic scheme (in axes 3 and 4) and 420 in the ILAE 2010 classification system. Leading categories were localization-related epilepsies, symptomatic focal epilepsies, perinatal insult, and epilepsies attributed to structural and metabolic cause in ILAE 1989, 2001 axis 3, 2001 axis 4, and 2010 systems, respectively. The ILAE 1989 classification system could categorize significantly greater numbers of patients compared to the 2001 and 2010 systems, whereas the latter two remained similar. SIGNIFICANCE: A large group of patients remained unclassified in the new classification system despite our tremendous gain in knowledge through improved imaging, genomics, and molecular biology, and so on, which could be attributed to lack of availability of facilities in developing countries. Dichotomy of localization-related and generalized epilepsy still makes for a fundamental and pragmatic working diagnosis and guides the physician about the extent of investigations and treatment especially in "epilepsies of unknown cause."
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Epilepsia/classificação , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Coleta de Dados , Eletroencefalografia , Epilepsia/diagnóstico , Epilepsia/terapia , Feminino , Genômica , Humanos , Índia , Lactente , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
The World Health Assembly approved the Intersectoral Global Action Plan for epilepsy and neurological disorders. Member states, including those in Southeast Asia, must now prepare to achieve IGAP's strategic targets by embracing novel approaches and strengthening existing policies and practices. We propose and present evidence to support four such processes. The opening course should engage all stakeholders to develop people-centric instead of outcome-centric approaches. Rather than caring for convulsive epilepsy alone, as currently done, primary care providers should also be skilled in diagnosing and treating focal and non-motor seizures. This could reduce the diagnostic gap as over half of epilepsies present with focal seizures. Currently, primary care providers lack knowledge and skills to manage focal seizures. Technology-enabled aids can help overcome this limitation. Lastly, there is need to add newer "easy to use" epilepsy medicines to Essential Medicines lists in light of emerging evidence for better tolerability, safety and user-friendliness.
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Background and Purpose: We aimed to explore the characteristics, clinical features, predictors of seizure, and associated clinical outcomes in patients with cerebral venous thrombosis (CVT). Methods: We enrolled patients with CVT from January 2014 to July 2020. Prospectively patients were recruited from December 2018. We analyzed predictors of seizures and associated good functional outcomes (modified Rankin Scale, mRS: 0-2) using multivariable logistic regression. Results: We enrolled 153 patients with CVT in which 77 (50%) had presented with a seizure. The median age was 31 years (IQR 16-46), and the majority were men (73.2%). Focal to bilateral tonic-clonic was the most common seizure type (27%), followed by generalized seizures (22%). None of the patients had status epilepticus. Antiseizure medications (ASM) were used in 71% of patients at diagnosis, 42% having received them prophylactically. Supratentorial parenchymal involvement was seen in 72% of seizure patients compared to 38% in those without, and superior sagittal sinus was most commonly involved. Percentage of patients who achieved good clinical outcome (mRS 0-2) at 3 months did not vary significantly between both groups. The only predictor for seizures with CVT was the presence of a parenchymal lesion (OR-3.75, 95% CI 1.79-7.85), whereas seizure occurrence (OR- 12.55, 95% CI- 1.53-102.59) was associated with statistically significant risk for recurrent seizures, by multiple logistic regression analysis. Seizure occurrence was not associated with adverse functional outcomes. Conclusion: Seizures at presentation occurred in 50% of patients with CVT which was associated with a parenchymal lesion in the brain. There was no association between seizure at presentation and clinical outcome.
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Background: Governments have imposed lockdowns in the wake of the COVID-19 pandemic. Hospitals have restricted outpatient clinics and elective services meant for non-COVID illnesses. This has led to patients facing unprecedented challenges and uncertainties. This study was carried out to assess patients' concerns and apprehensions about the effect of the lockdown on their treatments. Materials and Methods: An ambispective, observational cross-sectional single centre study was conducted. Patients were contacted telephonically and requested to answer a structured questionnaire. Their responses were documented and summarized as frequency and proportions. Results: A total of 727 patients were interviewed. Epilepsy (32%) was the most common neurological illness in our cohort followed by stroke (18%). About half the patients and/or their caregivers reported health-related concerns during the lockdown. The primary concern was how to connect with their treating neurologist if need arose. Forty-seven patients (6.4%) had drug default. Among patients on immunomodulatory treatments, only eight patients had drug default. High compliance rates were also observed in the stroke and epilepsy cohorts. Of the 71 patients who required emergency care during the lockdown, 24 could reach our hospital emergency. Fourteen patients either had a delay or could not seek emergency care. Two-thirds of our patients found the telemedicine experience satisfactory. Conclusion: The ongoing pandemic will continue to pose challenges to both physicians and patients. Patients in follow-up may need to be contacted regularly and counselled regarding the importance of maintaining drug compliance. Telemedicine can be used to strengthen the healthcare delivery to patients with non-COVID illnesses.
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Primary CNS Vasculitis (PCNSV) is a rare inflammatory disorder affecting the blood vessels of the central nervous system. Patients present with a combination of headaches, seizures, and focal neurological deficits. There is usually a diagnostic delay. Treatment is based on observational studies and expert opinion. Our objective was to identify clinical, laboratory, neuroimaging, pathologic or management-related associations with 2 year outcome in patients with primary CNS vasculitis. We conducted a cohort study at a single tertiary care referral centre of prospectively (2018-2019) and retrospectively (2010-2018) identified individuals with primary CNS vasculitis (diagnosis was proven by either brain biopsy or cerebral digital subtraction angiography). Clinical, imaging and histopathologic findings, treatment, and functional outcomes were recorded. Univariate and stepwise multiple logistic regression were applied. P-value<0.05 was considered statistically significant. The main outcome measures were documentation of clinical improvement or worsening (defined by mRS scores) and identification of independent predictors of good functional outcome (mRS 0-2) at 2 years. We enrolled eighty-two biopsy and/or angiographically proven PCNSV cases. The median age at presentation was 34 years with a male predilection and a median diagnostic delay of 23 months. Most patients presented with seizures (70.7%). All patients had haemorrhages on MRI. Histologically lymphocytic subtype was the commonest. Corticosteroids with cyclophosphamide was the commonest medication used. The median mRS at follow-up of 2 years was 2 (0-3), and 65.2% of patients achieved a good functional outcome. Myelitis and longer duration of illness before diagnosis were associated with poorer outcomes. The presence of hemorrhages on SWI sequence of MRI might be a sensitive imaging marker. Treatment with steroids and another immunosuppressant probably reduced relapse rates in our cohort. We have described the third largest PCNSV cohort and multi-centre randomised controlled trials are required to study the relative efficacy of various immunosuppressants.Study registration: CTRI/2018/03/012721.
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Vasculite do Sistema Nervoso Central , Angiografia Cerebral , Estudos de Coortes , Diagnóstico Tardio , Humanos , Imunossupressores/uso terapêutico , Masculino , Estudos Retrospectivos , Convulsões/complicações , Vasculite do Sistema Nervoso Central/diagnóstico por imagem , Vasculite do Sistema Nervoso Central/tratamento farmacológicoRESUMO
The ongoing COVID-19 pandemic has precipitated a global health crisis. Non-COVID diseases across specialties have been significantly compromised. The greatest challenge has been to continue providing care to non-COVID cases with minimum transmission risk to health care workers, patients, and caregivers. In this specter, better described as a medical holocaust, we present our experiences of dealing with acute neurological patients who could access our facility. We attempted to work on three key areas - initial screening using a more inclusive, dynamic checklist for COVID suspicion over and above the emergency triage, a mandatory initial holding on a separate floor of our inpatient service equipped with infection control strategies similar to a COVID-designated area, and daily screening of health care workers and caregivers for symptoms and possible exposures. It was a steep learning curve, a couple of close shaves, and many more lessons that went into the development of an algorithm that seems to be working well.
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Importance: There is an unmet need for safe and efficacious treatments for upper-extremity dystonic tremor (DT). To date, only uncontrolled retrospective case series have reported the effect of botulinum neurotoxin (BoNT) injections on upper-extremity DT. Objective: To assess the effect of BoNT injections on tremor in patients with upper-extremity DT. Design, Setting, and Participants: In this placebo-controlled, parallel-group randomized clinical trial, 30 adult patients with upper-extremity DT treated at a movement disorder clinic in a tertiary care university hospital were randomized in a 1:1 ratio to BoNT or saline injection, 0.9%, using a computer-generated randomization sequence. Randomization was masked using opaque envelopes. The participant, injector, outcome assessor, and statistician were blinded to the randomization. Participants were recruited between November 20, 2018, and December 12, 2019, and the last follow-up was completed in March 2020. Interventions: Participants received electromyographically guided intramuscular injections of BoNT or placebo into the tremulous muscles of the upper extremity. Injection patterns and doses were individualized according to tremor phenomenologic findings. Main Outcomes and Measures: The primary outcome was the total score on the Fahn-Tolosa-Marin Tremor Rating Scale 6 weeks after the intervention. Outcomes were assessed at baseline, 6 weeks, and 12 weeks. All patients were offered open-label BoNT injections after 12 weeks and reassessed 6 weeks later. Results: A total of 48 adult patients with a diagnosis of brachial dystonia with DT were screened. Fifteen were ineligible and 3 refused consent; therefore, 30 patients (mean [SD] age, 46.0 [18.6] years; 26 [86.7%] male) were recruited, with 15 randomized to receive BoNT and 15 to receive placebo. In the intention-to-treat group, the Fahn-Tolosa-Marin Tremor Rating Scale total score was significantly lower in the BoNT group at 6 weeks (adjusted mean difference, -10.9; 95% CI, -15.4 to -6.5; P < .001) and 12 weeks (adjusted mean difference, -5.7; 95% CI, -11.0 to -0.5; P = .03). More participants in the BoNT group reported global improvement on the Global Impression of Change (PGIC) assessment (PGIC 1, 2, and 3: BoNT: 4 [26.7%], 6 [40.0%], and 5 [33.3%]; placebo: 5 [33.3%], 10 [66.7%], and 0, respectively; P = .047). Subjective hand weakness (BoNT: 6 [40.0%]; placebo: 4 [28.6%], P = .52) and dynamometer-assessed grip strength (mean difference, -0.2 log10[kgf/m2]2/Hz-Hz; 95% CI, -0.9 to 0.4 log10[kgf/m2]2/Hz-Hz; P = .45) were similar in both groups. Conclusions and Relevance: In this randomized clinical trial, botulinum neurotoxin injections were superior to placebo in reducing tremor severity in upper-extremity DT. An individualized approach to muscle selection and dosing was beneficial without unacceptable adverse effects. Trial Registration: Clinical Trials Registry of India (http://ctri.nic.in) Identifier: CTRI/2018/02/011721.
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Toxinas Botulínicas Tipo A/administração & dosagem , Distonia/diagnóstico , Distonia/tratamento farmacológico , Mãos/patologia , Fármacos Neuromusculares/administração & dosagem , Tremor/diagnóstico , Tremor/tratamento farmacológico , Adulto , Idoso , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Injeções Intramusculares/métodos , Masculino , Pessoa de Meia-Idade , Extremidade SuperiorRESUMO
OBJECTIVES: Patients with muscle-specific kinase (MuSK)-positive myasthenia are generally considered to have a grave prognosis. We present our experience of patients with myasthenia with different antibody status. This is followed by a short discourse on previous studies and the current view on MuSK-positive myasthenia, focusing on the associated prejudice. MATERIALS AND METHODS: This study compares 23 patients with MuSK-positive myasthenia with 55 patients with acetylcholine receptor-positive myasthenia and 9 patients with double-seronegative myasthenia at a tertiary level center. RESULTS: We did not find any significant difference in terms of clinical characteristics, treatment response to immunosuppressants, long-term prognosis, and quality of life. CONCLUSION: Seropositivity for antibodies should not be used in isolation to guide the management or predict the prognosis. Undue negative prognostication may affect the morale of patient. Clinical features and response to therapy in addition to antibody status must be considered before planning therapy.
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Antiparasitic treatment improves the prognosis for neurocysticercosis (NCC)-induced seizures. However, patients with high lesion loads are typically denied the possible benefit of cysticidal therapy because of fear of complications, and such patients are not represented in clinical trials involving cysticidal therapy. We provide proof of concept for combination treatment with dual antiparasitic therapy and corticosteroids in patients with diffuse lesions, including starry sky patterns, or calcific NCC. The safety and efficacy of treating patients with high lesion loads or calcific NCC should be tested in a randomized controlled trial.
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Antiparasitários/uso terapêutico , Calcificação Fisiológica/efeitos dos fármacos , Neurocisticercose/diagnóstico por imagem , Neurocisticercose/tratamento farmacológico , Taenia solium/efeitos dos fármacos , Adolescente , Corticosteroides/uso terapêutico , Adulto , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Neurocisticercose/parasitologia , Prognóstico , Convulsões/etiologia , Taenia solium/patogenicidade , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
BACKGROUND: Anticholinergic drugs are associated with significant cognitive and other adverse events in older adults, including those with Parkinson's disease (PD). Anticholinergic effects are considered lesser in younger individuals and the burden and outcomes in younger patients with PD are unknown. OBJECTIVES: To determine the cumulative anticholinergic burden in a cohort of younger of patients with PD and to correlate the same with cognitive impairment and freezing of gait (FOG). METHODS: We conducted a cross-sectional study to identify the cumulative anticholinergic burden from medications prescribed to patients with PD. Two standard scales, the Anticholinergic Cognitive Burden (ACB) scale and the ACB score, were used to calculate the anticholinergic burden from prescriptions. We identified commonly prescribed drugs contributing to anticholinergic effects and correlated the cumulative ACB score with cognitive impairment (Movement Disorder Society-Unified Parkinson's Disease Rating Scale item 1.1) and FOG (Movement Disorder Society-Unified Parkinson's Disease Rating Scale items 2.13 and 3.11). RESULTS: We recruited 287 patients with PD (68.9% male) with a mean age of 56.9 ± 11.8 years and a duration of symptoms 6.3 ± 6.9 years. Median ACB score was 4 (range 0-12). A total of 164 (58.4%) patients had total ACB score > 3. ACB score > 3 was independently associated with cognitive impairment (Odds Ratio, 2.55; 95% confidence interval, 1.43-4.53; P < 0.001) and FOG using patient-reported measures (Odds Ratio, 3.192; 95% Confidence Interval, 1.68-6.07; P < 0.001) and objective measures (odds ratio, 2.41; 95% confidence interval, 1.27-4.6, P = 0.007). CONCLUSION: Patients with PD are exposed to significant anticholinergic burden from drugs prescribed for PD and non-PD indications. Higher anticholinergic burden is associated with cognitive impairment and FOG even in younger patients with PD.