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.
To evaluate the effects of corticosteroids as an adjunct to antituberculous treatment on death and severe disability in people with tuberculous meningitis.
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.
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.
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.
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.
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.
Abstract
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.
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.
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.
Abstract Background: Acute kidney injury (AKI) is prevalent in patients with acute stroke. Although AKI is linked to poor clinical outcomes, data about its incidence and effect on stroke outcomes is ...limited. Methods: This was a prospective observational study carried out at a single tertiary care center that analyzed the data of 204 consecutive subjects with acute ischemic stroke and intracerebral hemorrhage. Considering serum creatinine at admission as the baseline, AKI was defined as a rise in serum creatinine value of 0.3 mg/dl over 48 h or a percentage increase of at least 50% from baseline over 7 days during hospitalization. The primary outcome was to measure the prevalence of AKI in patients with acute stroke. Secondary outcome measures were all-cause mortality, duration of hospital stay, need for dialysis, and comparison of outcomes in ischemic and hemorrhagic stroke. For both the stroke subtypes, we employed a multivariate logistic regression model, with AKI and hospital mortality being the outcomes. Covariates included gender, age, ventilatory requirement, duration of hospital stay, and National Institutes of Health Stroke Scale score at admission. Results: There were 144 cases of ischemic stroke with 12 deaths (8.3%) and 60 cases of intracranial hemorrhage (ICH) with 22 deaths (36.7%). The mean age was 55 years, 72.6% were males, and AKI complicated 34% of ischemic stroke and 66.7% of ICH hospitalizations. AKI was linked to increased hospital mortality from ischemic stroke (odds ratio OR 27.21, 95% CI 3.39–218.13) and hemorrhagic stroke (OR 5.12, 95% CI 1.29–20.28) in multivariate analysis stratified by stroke type. Conclusions: AKI complicates stroke frequently and increases hospital mortality. Additional studies are required to assess if the association is causal and if remedies to prevent AKI would decrease mortality.
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.
To assess the effect of BoNT injections on tremor in patients with upper-extremity DT.
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.
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.
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.
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 log10kgf/m22/Hz-Hz; 95% CI, -0.9 to 0.4 log10kgf/m22/Hz-Hz; P = .45) were similar in both groups.
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.
Clinical Trials Registry of India (http://ctri.nic.in) Identifier: CTRI/2018/02/011721.
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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