Autoimmune Encephalitis: A Hidden Enigma Demystified.

Autoimmune encephalitis is a condition marked by inflammation in the brain due to an immune system response targeting self-antigens within the central nervous system (CNS). This class of disorders is at least as prevalent as infectious causes of encephalitis and encompasses a wide range of conditions. The field has rapidly expanded thanks to the identification of various pathogenic autoantibodies responsible for varied neurological and neuropsychiatric diseases. These disorders often present with distinct cognitive, seizure, and movement disorder phenotypes, making them clinically identifiable. Swift identification and treatment are pivotal for improving patient outcomes and promptly diagnosing associated tumors. This article zeroes in on autoantibody-mediated encephalitis syndromes involving neuronal cell-surface antigens. It sheds light on practical aspects of diagnosis and treatment, drawing from clinical experiences in managing such cases. Additionally, it underscores the ongoing importance of neuroimmunological advances that will shape the future diagnosis and treatment of these conditions.

SARS-CoV-2-associated haemorrhagic encephalitis mimicking Herpes encephalitis.

Although acute encephalopathy is quite commonly seen in patients of SARS-CoV-2 infection, encephalitis characterised by brain inflammation is relatively rare. Encephalitis caused by Herpes simplex type 1 is the most common cause of identified sporadic encephalitis, and early diagnosis and prompt treatment can prevent the devastating outcome. In this brief communication, we report a case of SARS-CoV-2 associated haemorrhagic encephalitis mimicking herpes encephalitis. In today's pandemic era, it is especially important to distinguish herpes encephalitis from SARS-CoV-2-associated encephalitis as treatment and prognosis of both the conditions differ greatly. This case highlights the importance of suspecting SARS-CoV-2 infection in a patient presenting with clinical symptoms and brain imaging suggestive of Herpes encephalitis.

Stroke Care during the COVID-19 Pandemic: International Expert Panel Review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has placed a tremendous strain on healthcare services. This study, prepared by a large international panel of stroke experts, assesses the rapidly growing research and personal experience with COVID-19 stroke and offers recommendations for stroke management in this challenging new setting: modifications needed for prehospital emergency rescue and hyperacute care; inpatient intensive or stroke units; posthospitalization rehabilitation; follow-up including at-risk family and community; and multispecialty departmental developments in the allied professions. SUMMARY: The severe acute respiratory syndrome coronavirus 2 uses spike proteins binding to tissue angiotensin-converting enzyme (ACE)-2 receptors, most often through the respiratory system by virus inhalation and thence to other susceptible organ systems, leading to COVID-19. Clinicians facing the many etiologies for stroke have been sobered by the unusual incidence of combined etiologies and presentations, prominent among them are vasculitis, cardiomyopathy, hypercoagulable state, and endothelial dysfunction. International standards of acute stroke management remain in force, but COVID-19 adds the burdens of personal protections for the patient, rescue, and hospital staff and for some even into the postdischarge phase. For pending COVID-19 determination and also for those shown to be COVID-19 affected, strict infection control is needed at all times to reduce spread of infection and to protect healthcare staff, using the wealth of well-described methods. For COVID-19 patients with stroke, thrombolysis and thrombectomy should be continued, and the usual early management of hypertension applies, save that recent work suggests continuing ACE inhibitors and ARBs. Prothrombotic states, some acute and severe, encourage prophylactic LMWH unless bleeding risk is high. COVID-19-related cardiomyopathy adds risk of cardioembolic stroke, where heparin or warfarin may be preferable, with experience accumulating with DOACs. As ever, arteritis can prove a difficult diagnosis, especially if not obvious on the acute angiogram done for clot extraction. This field is under rapid development and may generate management recommendations which are as yet unsettled, even undiscovered. Beyond the acute management phase, COVID-19-related stroke also forces rehabilitation services to use protective precautions. As with all stroke patients, health workers should be aware of symptoms of depression, anxiety, insomnia, and/or distress developing in their patients and caregivers. Postdischarge outpatient care currently includes continued secondary prevention measures. Although hoping a COVID-19 stroke patient can be considered cured of the virus, those concerned for contact safety can take comfort in the increasing use of telemedicine, which is itself a growing source of patient-physician contacts. Many online resources are available to patients and physicians. Like prior challenges, stroke care teams will also overcome this one. Key Messages: Evidence-based stroke management should continue to be provided throughout the patient care journey, while strict infection control measures are enforced.

Sonographic pattern of median nerve enlargement in Hansen's neuropathy.

OBJECTIVES: Median nerve enlargement in leprosy seems to be more proximal than in carpal tunnel syndrome (CTS), but this feature has not been studied systematically. The aim of the study was to compare the sites of median nerve enlargement in patients with leprosy with that of patients with CTS. MATERIALS AND METHODS: Transverse sections of the median nerve were recorded from wrist to the mid-forearm (at distal wrist crease and at 2-cm: M1, 4-cm: M2, 6-cm: M3, 8-cm: M4 and 10-cm: M5, proximal to the distal wrist crease in the forearm) in patients with leprosy, CTS and healthy subjects using high-resolution ultrasound. RESULTS: Twenty-six patients each with leprosy and CTS were compared with healthy controls. Patients with leprosy included 6 (23.1%), 7 (26.9%), 7 (26.9%) and 6 (23.1%) patients with borderline tuberculoid, borderline-borderline, borderline lepromatous and lepromatous leprosy, respectively. Cross-sectional area (CSA) of median nerve was increased in all patients with leprosy as compared to healthy controls at all points of measurement. CSA was higher among patients with leprosy as compared to CTS at all points except at the wrist. In patients with leprosy, the maximal enlargement was noted 2-cm (M1) proximal to the wrist crease with gradual tapering of the CSA proximally (p < .05). In contrast, in patients with CTS the median nerve was maximally enlarged at the distal wrist crease (p<.05). CONCLUSIONS: Median nerve enlargement 2-cm proximal to the distal wrist crease distinguishes leprosy from CTS. This important discriminating sign can be used at point-of-care to identify patients with leprosy.

Morbidity and mortality from road injuries: results from the Global Burden of Disease Study 2017.

BACKGROUND: The global burden of road injuries is known to follow complex geographical, temporal and demographic patterns. While health loss from road injuries is a major topic of global importance, there has been no recent comprehensive assessment that includes estimates for every age group, sex and country over recent years. METHODS: We used results from the Global Burden of Disease (GBD) 2017 study to report incidence, prevalence, years lived with disability, deaths, years of life lost and disability-adjusted life years for all locations in the GBD 2017 hierarchy from 1990 to 2017 for road injuries. Second, we measured mortality-to-incidence ratios by location. Third, we assessed the distribution of the natures of injury (eg, traumatic brain injury) that result from each road injury. RESULTS: Globally, 1 243 068 (95% uncertainty interval 1 191 889 to 1 276 940) people died from road injuries in 2017 out of 54 192 330 (47 381 583 to 61 645 891) new cases of road injuries. Age-standardised incidence rates of road injuries increased between 1990 and 2017, while mortality rates decreased. Regionally, age-standardised mortality rates decreased in all but two regions, South Asia and Southern Latin America, where rates did not change significantly. Nine of 21 GBD regions experienced significant increases in age-standardised incidence rates, while 10 experienced significant decreases and two experienced no significant change. CONCLUSIONS: While road injury mortality has improved in recent decades, there are worsening rates of incidence and significant geographical heterogeneity. These findings indicate that more research is needed to better understand how road injuries can be prevented.

Strategies to Improve Stroke Care Services in Low- and Middle-Income Countries: A Systematic Review.

BACKGROUND: The burden of stroke in low- and middle-income countries (LMICs) is large and increasing, challenging the already stretched health-care services. AIMS AND OBJECTIVES: To determine the quality of existing stroke-care services in LMICs and to highlight indigenous, inexpensive, evidence-based implementable strategies being used in stroke-care. METHODS: A detailed literature search was undertaken using PubMed and Google scholar from January 1966 to October 2015 using a range of search terms. Of 921 publications, 373 papers were shortlisted and 31 articles on existing stroke-services were included. RESULTS: We identified efficient models of ambulance transport and pre-notification. Stroke Units (SU) are available in some countries, but are relatively sparse and mostly provided by the private sector. Very few patients were thrombolysed; this could be increased with telemedicine and governmental subsidies. Adherence to secondary preventive drugs is affected by limited availability and affordability, emphasizing the importance of primary prevention. Training of paramedics, care-givers and nurses in post-stroke care is feasible. CONCLUSION: In this systematic review, we found several reports on evidence-based implementable stroke services in LMICs. Some strategies are economic, feasible and reproducible but remain untested. Data on their outcomes and sustainability is limited. Further research on implementation of locally and regionally adapted stroke-services and cost-effective secondary prevention programs should be a priority.

Corticosteroids for chronic inflammatory demyelinating polyradiculoneuropathy.

BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a progressive or relapsing and remitting paralysing illness, probably due to an autoimmune response, which should benefit from corticosteroid treatment. Non-randomised studies suggest that corticosteroids are beneficial. Two commonly used corticosteroids are prednisone and prednisolone. Both are usually given as oral tablets. Prednisone is converted into prednisolone in the liver so that the effect of the two drugs is usually the same. Another corticosteroid, dexamethasone, is more potent and is used in smaller doses. The review was first published in 2001 and last updated in 2015; we undertook this update to identify any new evidence. OBJECTIVES: To assess the effects of corticosteroid treatment for CIDP compared to placebo or no treatment, and to compare the effects of different corticosteroid regimens. SEARCH METHODS: On 8 November 2016, we searched the Cochrane Neuromuscular Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, and Embase for randomised trials of corticosteroids for CIDP. We searched clinical trials registries for ongoing trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs of treatment with any corticosteroid or adrenocorticotrophic hormone for CIDP, diagnosed by an internationally accepted definition. DATA COLLECTION AND ANALYSIS: Two authors extracted data from included studies and assessed the risk of bias independently. The intended primary outcome was change in disability, with change in impairment after 12 weeks and side effects as secondary outcomes. We assessed strength of evidence using the GRADE approach. MAIN RESULTS: One non-blinded RCT comparing prednisone with no treatment in 35 eligible participants did not measure the primary outcome for this systematic review. The trial had a high risk of bias. Neuropathy Impairment Scale scores after 12 weeks improved in 12 of 19 participants randomised to prednisone, compared with five of 16 participants randomised to no treatment (risk ratio (RR) for improvement 2.02 (95% confidence interval (CI) 0.90 to 4.52; very low-quality evidence). The trial did not report side effects in detail, but one prednisone-treated participant died.A double-blind RCT comparing daily standard-dose oral prednisolone with monthly high-dose oral dexamethasone in 40 participants reported none of the prespecified outcomes for this review. The trial had a low risk of bias, but the quality of evidence was limited as it came from a single small study. There was little or no difference in number of participants who achieved remission (RR 1.11; 95% CI 0.50 to 2.45 in favour of monthly dexamethasone; moderate-quality evidence), or change in disability or impairment after one year (low-quality evidence). Change of grip strength or Medical Research Council (MRC) scores demonstrated little or no difference between groups (moderate-quality to low-quality evidence). Eight of 16 people in the prednisolone group and seven of 24 people in the dexamethasone group deteriorated. Side effects were similar with each regimen, except that sleeplessness was less common with monthly dexamethasone (low-quality evidence) as was moon facies (moon-shaped appearance of the face) (moderate-quality evidence).Experience from large non-randomised studies suggests that corticosteroids are beneficial, but long-term use causes serious side effects. AUTHORS' CONCLUSIONS: We are very uncertain about the effects of oral prednisone compared with no treatment, because the quality of evidence from the only RCT that exists is very low. Nevertheless, corticosteroids are commonly used in practice, supported by very low-quality evidence from observational studies. We also know from observational studies that corticosteroids carry the long-term risk of serious side effects. The efficacy of high-dose monthly oral dexamethasone is probably little different from that of daily standard-dose oral prednisolone. Most side effects occurred with similar frequencies in both groups, but with high-dose monthly oral dexamethasone moon facies is probably less common and sleeplessness may be less common than with oral prednisolone. We need further research to identify factors that predict response.

The dilemma of arranged marriages in people with epilepsy. An expert group appraisal.

INTRODUCTION: Matrimony remains a challenging psychosocial problem confronting people with epilepsy (PWE). People with epilepsy are less likely to marry; however, their marital prospects are most seriously compromised in arranged marriages. AIMS: The aim of this study was to document marital prospects and outcomes in PWE going through arranged marriage and to propose optimal practices for counseling PWE contemplating arranged marriage. METHODS: A MEDLINE search and literature review were conducted, followed by a cross-disciplinary meeting of experts to generate consensus. RESULTS: People with epilepsy experience high levels of felt and enacted stigma in arranged marriages, but the repercussions are heavily biased against women. Hiding epilepsy is common during marital negotiations but may be associated with poor medication adherence, reduced physician visits, and poor marital outcome. Although divorce rates are generally insubstantial in PWE, divorce rates appear to be higher in PWE undergoing arranged marriages. In these marriages, hiding epilepsy during marital negotiations is a risk factor for divorce. CONCLUSIONS: In communities in which arranged marriages are common, physicians caring for PWE are best-equipped to counsel them about their marital prospects. Marital plans and aspirations should be discussed with the family of the person with epilepsy in a timely and proactive manner. The benefits of disclosing epilepsy during marital negotiations should be underscored.

Implications of female sex on stroke risk factors, care, outcome and rehabilitation: an Asian perspective.

BACKGROUND: Stroke affects 16.9 million people annually and the greatest burden of stroke is in low- and middle-income countries, where 69% of all strokes occur. Stroke risk factors, mortality and outcomes differ in developing countries as compared to the developed world. We performed a literature review of 28 articles pertaining to epidemiology of stroke in Asian women, stroke risk factors, gender-related differences, and stroke outcomes. SUMMARY: Asian women differ from women worldwide due to differences in stroke awareness, risk factor profile, stroke subtypes, and social issues that impact stroke care. While Asian men have a higher incidence of stroke as compared to women overall, the long- and short-term outcomes in Asian women tend to be poorer. Both conventional and gender-specific risk factors contribute to stroke risk. Oral contraceptive use and addictions such as tobacco and alcohol are less prevalent among Asian women due to socio cultural differences. There is however, a much higher preponderance of pregnancy-related stroke and cardio-embolic stroke secondary to rheumatic heart disease and heavy use of chewing tobacco. The overall outcome is poor due to poor access to health care and lack of resources. Key Messages: Our review exposed the gaps in our knowledge about stroke risk factors and differences in stroke care provided to Asian women. While there are sociocultural barriers that impede the provision of immediate care to these stroke patients, much needs to be done by way of prevention of recurrent stroke and treatment of risk factors.

Plasma exchange for chronic inflammatory demyelinating polyradiculoneuropathy.

BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an uncommon progressive or relapsing paralysing disease caused by inflammation of the peripheral nerves. If the hypothesis that it is due to autoimmunity is correct, removal of autoantibodies in the blood by plasma exchange should be beneficial. OBJECTIVES: To assess the effects of plasma exchange for treating CIDP. SEARCH METHODS: On 30 June 2015, we searched the Cochrane Neuromuscular Disease Group Specialized Register, the Cochrane Central Register for Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL Plus, and LILACS. We also scrutinised the bibliographies of the trials, contacted the trial authors and other disease experts, and searched trials registries for ongoing studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs in participants of any age comparing plasma exchange with sham treatment or no treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the trials, extracted the data, and assessed risk of bias. Where possible the review authors combined data according to the methods of the Cochrane Neuromuscular Disease Review Group. PRIMARY OUTCOME MEASURE: one cross-over trial including 18 participants showed after four weeks, 2 (95% confidence interval (CI) 0.8 to 3.0) points more improvement on an 11-point disability scale with plasma exchange (10 exchanges over four weeks) than with sham exchange. Rapid deterioration after plasma exchange occurred in eight of 12 who had improved. SECONDARY OUTCOME MEASURES: when we combined the results of this cross-over trial and a trial with 29 participants treated in a parallel-group design, there were 31 points (95% CI 16 to 45) more improvement on an impairment scale (maximum score 280) after plasma exchange (six exchanges over three weeks) than after sham exchange. There were significant improvements in both trials in an electrophysiological measure, the proximally evoked compound muscle action potential, after three or four weeks. Nonrandomised evidence indicates that plasma exchange induces adverse events in 3% to 17% of procedures. These events are sometimes serious. Both trials had a low risk of bias. A trial that showed no significant difference in the benefit between plasma exchange and intravenous immunoglobulin is included in the Cochrane review of intravenous immunoglobulin for this condition. AUTHORS' CONCLUSIONS: Moderate- to high-quality evidence from two small trials shows that plasma exchange provides significant short-term improvement in disability, clinical impairment, and motor nerve conduction velocity in CIDP but rapid deterioration may occur afterwards. Adverse events related to difficulty with venous access, use of citrate, and haemodynamic changes are not uncommon. We need more research to identify agents that will prolong the beneficial action of plasma exchange.

Corticosteroids for chronic inflammatory demyelinating polyradiculoneuropathy.

BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a progressive or relapsing and remitting paralysing illness probably due to an autoimmune response which should benefit from corticosteroids. Non-randomised studies suggest that corticosteroids are beneficial. Two commonly used corticosteroids are prednisone and prednisolone. Both are usually given as oral tablets. Prednisone is converted into prednisolone in the liver so that the effect of the two drugs is usually the same. Another corticosteroid, called dexamethasone, is more potent and is used in smaller doses. OBJECTIVES: To assess the effects of corticosteroid treatment compared to placebo or no treatment for CIDP and to compare the effects of different corticosteroid regimes. SEARCH METHODS: On 27 October 2014 we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, and EMBASE for randomised trials of corticosteroids for CIDP. We searched three other databases for information to include in the Discussion, and clinical trials registries for ongoing trials. SELECTION CRITERIA: We included randomised or quasi-randomised trials of treatment with any form of corticosteroids or adrenocorticotrophic hormone for CIDP, diagnosed by an internationally accepted definition. DATA COLLECTION AND ANALYSIS: Two authors extracted the data and assessed risk of bias independently. The primary outcome was intended to be change in disability, with change in impairment after 12 weeks as a secondary outcome, and adverse events. MAIN RESULTS: In one non-blinded randomised controlled trial (RCT) with 35 eligible participants, the primary outcome for this review was not available. The trial had a high risk of bias. Twelve of 19 participants treated with prednisone, compared with five of 16 participants randomised to no treatment, had improved neuropathy impairment scores after 12 weeks; the risk ratio (RR) for improvement was 2.02 (95% confidence interval (CI) 0.90 to 4.52). Adverse events were not reported in detail, but one prednisone-treated participant died.In a double-blind RCT comparing daily standard-dose oral prednisolone with monthly high-dose oral dexamethasone in 40 participants, none of the outcomes for this review were available. The trial had a low risk of bias. There were no significant differences in remission (RR 1.11; 95% CI 0.50 to 2.45 in favour of monthly dexamethasone) or change in disability or impairment after one year. Eight of 16 in the prednisolone, and seven of 24 in the dexamethasone group deteriorated. Adverse events were similar with each regimen, except that sleeplessness and moon facies (moon-shaped appearance of the face) were significantly less common with monthly dexamethasone.Experience from large non-randomised studies suggests that corticosteroids are beneficial, but long-term use causes serious side effects. AUTHORS' CONCLUSIONS: Very low quality evidence from one small, randomised trial did not show a statistically significant benefit from oral prednisone compared with no treatment. Nevertheless, corticosteroids are commonly used in practice. According to moderate quality evidence from one RCT, the efficacy of high-dose monthly oral dexamethasone was not statistically different from that of daily standard-dose oral prednisolone. Most adverse events occurred with similar frequencies in both groups, but sleeplessness and moon facies were significantly less common with monthly dexamethasone. Further research is needed to identify factors which predict response.

Stroke in Asia: geographical variations and temporal trends.

Asian countries are in various stages of epidemiological transition and therefore exhibit a great diversity in disease patterns. Collectively, they comprise almost two-third of the world's total mortality due to stroke. The purpose of this review is to explore existing epidemiological data on stroke, highlight the temporal trends in stroke epidemiology in various regions of Asia and predict future patterns based on these observations. Our search revealed that there is a lack of good epidemiological data from most Asian countries. Whatever data exist are not comparable due to lack of standardised methodology for ascertaining stroke and its subtypes. For this and other reasons, these estimates exhibit country-to-country variation and also within-country variability. We have also reviewed temporal trends in stroke incidence and prevalence in 12 Asian countries and the evolution of stroke subtypes over the past two decades. Important observations include a rise in stroke incidence in most Asian countries, an earlier age at onset compared with the West, a relative increase in the proportion of ischaemic strokes and a decline in haemorrhagic strokes. Among ischaemic stroke subtypes, lacunar strokes, which were once the commonest variety, are now declining. Emerging data suggest that large artery atherosclerosis and in particular that of intracranial vessels is the predominant aetiology in most Asian countries. The review also identified important gender differences in terms of stroke risk factors, prevalence and outcomes. There is need for sound epidemiological data from most countries to understand the disease better and plan policy-level interventions to decrease the burden. We identify a need for standard format or guidelines for conducting stroke epidemiological studies especially in developing Asian countries. This region must be identified as a priority region for stroke-related interventions and preventive strategies by global healthcare authorities and organisations.

Cerebral infarction and tuberculoma in central nervous system tuberculosis: frequency and prognostic implications.

BACKGROUND: Tuberculoma and cerebral infarctions are serious complications of central nervous system (CNS) tuberculosis. However, there are no studies comparing prognostic value of tuberculoma and infarcts alone and in patients diagnosed with CNS tuberculosis. OBJECTIVE: The objective of this study was to identify frequency and prognostic value of tuberculoma and cerebral infarcts in a large sample of CNS tuberculosis patients. METHODS: Retrospective chart review of patients diagnosed with CNS tuberculosis in a tertiary care hospital in Pakistan over 10-year period was carried out. RESULTS: There were 404 patients included in this study (mean age of 43 years). There were 209 (52%) men and 195 (48%) women. Tuberculoma were present in 202 subjects (50%) while infarcts were present in 25% patients. 147 (36%) had tuberculous meningitis (TBM) without tuberculoma or infarction on CT or MRI, 158 (39%) had TBM with intracranial tuberculomas, 60 (15%) had TBM with cerebral infarction while 39 (10%) had TBM with both tuberculoma and infarction. At discharge, 249 patients (62%) were either normal (Modified Rankin Score (MRS)=0) or mild to moderately disabled (MRS=1-3) while 82 patients (20%) had severe disability (MRS=4-5). 73 (18%) patients died (MRS=6) during hospitalisation. Using logistic regression analysis, significant predictors of poor outcome included old age, high TBM grading, presence of infarction and presence of hydrocephalus. CONCLUSIONS: Tuberculomas were present in 50% of patients, while infarcts were present in 25%. Old age, TBM grading, presence of infarction and hydrocephalus were all predictors of poor outcome.

Acetylcholinesterase inhibitor treatment for myasthenia gravis.

BACKGROUND: In myasthenia gravis, antibody-mediated blockade of acetylcholine receptors at the neuromuscular junction abolishes the naturally occurring 'safety factor' of synaptic transmission. Acetylcholinesterase inhibitors provide temporary symptomatic treatment of muscle weakness but there is controversy about their long-term efficacy, dosage and side effects. This is the second update of a review published in The Cochrane Library Issue 2, 2011. OBJECTIVES: To evaluate the efficacy of acetylcholinesterase inhibitors in all forms of myasthenia gravis. SEARCH METHODS: On 8 July 2014 we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE and EMBASE for randomised controlled trials and quasi-randomised controlled trials regarding usage of acetylcholinesterase inhibitors in myasthenia gravis. Two authors scanned the articles for any study eligible for inclusion. We also contacted the authors and known experts in the field to identify additional published or unpublished data and searched clinical trials registries for ongoing trials. SELECTION CRITERIA: The types of studies were randomised or quasi-randomised trials. Participants were myasthenia gravis patients diagnosed by an internationally accepted definition. The intervention was treatment with any form of acetylcholinesterase inhibitor. Types of outcome measures Primary outcome measureImprovement in the presenting symptoms within one to 14 days of the start of treatment. Secondary outcome measures(1) Improvement in the presenting symptoms more than 14 days after the start of treatment.(2) Change in impairment measured by a recognised and preferably validated scale, such as the quantitative myasthenia gravis score, within one to 14 days and more than 14 days after the start of treatment.(3) Myasthenia Gravis Association of America post-intervention status more than 14 days after start of treatment.(4) Adverse events including muscarinic side effects. DATA COLLECTION AND ANALYSIS: One author (MMM) extracted the data, which were checked by a second author. We contacted study authors for extra information and collected data on adverse effects from the trials. MAIN RESULTS: We did not find any large randomised or quasi-randomised trials of acetylcholinesterase inhibitors in generalised myasthenia gravis either for the first version of this review or this update. One cross-over randomised trial using intranasal neostigmine in a total of 10 participants was only available as an abstract. It included three participants with ocular myasthenia gravis and seven with generalised myasthenia gravis. Symptoms of myasthenia gravis (measured as improvement in at least one muscle function) improved in nine of the 10 participants after the two-week neostigmine treatment phase. No participant improved after the placebo phase. Lack of detail in the report meant that the risk of bias was unclear. Adverse events were minor. AUTHORS' CONCLUSIONS: Except for one small and inconclusive trial of intranasal neostigmine, no other randomised controlled trials have been conducted on the use of acetylcholinesterase inhibitors in myasthenia gravis. The response to acetylcholinesterase inhibitors in observational studies is so clear that a randomised controlled trial depriving participants in a placebo arm of treatment would be difficult to justify.

The international league against epilepsy primary healthcare educational curriculum: Assessment of educational needs.

OBJECTIVE: To assess the need for an epilepsy educational curriculum for primary healthcare providers formulated by the International League Against Epilepsy (ILAE) and the importance attributed to its competencies by epilepsy specialists and primary care providers and across country-income settings. METHODS: The ILAE primary care epilepsy curriculum was translated to five languages. A structured questionnaire assessing the importance of its 26 curricular competencies was posted online and publicized widely to an international community. Respondents included epilepsy specialists, primary care providers, and others from three World Bank country-income categories. Responses from different groups were compared with univariate and ordinal logistic regression analyses. RESULTS: Of 785 respondents, 60% noted that a primary care epilepsy curriculum did not exist or they were unaware of one in their country. Median ranks of importance for all competencies were high (very important to extremely important) in the entire sample and across different groups. Fewer primary care providers than specialists rated the following competencies as extremely important: definition of epilepsy (p = .03), recognition of seizure mimics (p = .02), interpretation of test results for epilepsy care (p = .001), identification of drug-resistant epilepsy (0.005) and management of psychiatric comorbidities (0.05). Likewise, fewer respondents from LMICs in comparison to UMICs rated 15 competencies as extremely important. SIGNIFICANCE: The survey underscores the unmet need for an epilepsy curriculum in primary care and the relevance of its competencies across different vocational and socioeconomic settings. Differences across vocational and country income groups indicate that educational packages should be developed and adapted to needs in different settings.

Comparative Study of Cerebral Venous Thrombosis-Risk Factors, Clinical Course, and Outcome in Subjects with and without COVID-19 Infection.

BACKGROUND/OBJECTIVE: Cerebral venous thrombosis (CVT) has been increasingly reported in patients with COVID-19. Most published literature is descriptive and focuses only on CVT in COVID-19 patients. The objective of our study was to compare CVT patients' characteristics with and without an associated COVID-19 infection. MATERIALS AND METHODS: This is a retrospective cross-sectional study. All adult patients with a confirmed diagnosis of CVT admitted to our hospital over a period of 30 months, from January 2019 to June 2021, were included. They were further divided into two groups, with and without COVID-19 infection. RESULTS: A total of 115 CVT patients were included, 93 in non-COVID-CVT and 22 in COVID-CVT group. COVID-CVT patients were male predominant and of older age, with longer hospital stay, and higher inpatient mortality. COVID-CVT patients presented with a higher frequency of headache (82% vs. 63%), seizures (64% vs. 37%, p = 0.03), hemiparesis (41% vs. 24%), and visual changes (36% vs. 19%) as compared to non-COVID-CVT patients. Venogram showed a higher frequency of superior sagittal sinus (64% vs. 42%) and internal jugular vein (23% vs. 12%) involvement in the COVID-CVT cohort. More than 90% of patients in both groups received therapeutic anticoagulation. Mortality rates were higher in COVID-CVT group (18% vs. 11%). CONCLUSION: COVID-CVT patients were male predominant and of older age, with higher hospital stay, and higher inpatient mortality as compared to non-COVID-CVT patients.

Corticosteroids for chronic inflammatory demyelinating polyradiculoneuropathy.

BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a progressive or relapsing and remitting paralysing illness probably due to an autoimmune response which should benefit from corticosteroids. Non-randomised studies suggest that corticosteroids are beneficial. Two commonly used corticosteroids are prednisone and prednisolone. Both are usually given as oral tablets. Prednisone is converted into prednisolone in the liver so that the effect of the two drugs is usually the same. Another corticosteroid, called dexamethasone, is more potent and is used in smaller doses. OBJECTIVES: To evaluate the efficacy of corticosteroid treatment compared to placebo or no treatment for CIDP and to compare the efficacy of different corticosteroid regimes. SEARCH METHODS: We searched the Cochrane Neuromuscular Disease Group Specialized Register (20 February 2012), CENTRAL (2012, Issue 2), MEDLINE (January 1966 to February 2012), and EMBASE (January 1980 to February 2012) for randomised trials of corticosteroids for CIDP. SELECTION CRITERIA: We included randomised or quasi-randomised trials of treatment with any form of corticosteroids or adrenocorticotrophic hormone for CIDP, diagnosed by an internationally accepted definition. DATA COLLECTION AND ANALYSIS: Two authors extracted the data and assessed risk of bias independently. The primary outcome was intended to be change in disability, with secondary outcomes of change in impairment, maximum motor nerve conduction velocity, or compound muscle action potential amplitude after 12 weeks, and adverse events. MAIN RESULTS: In one non-blinded randomised controlled trial (RCT) with 35 eligible participants, the primary outcome for this review was not available. Twelve of 19 participants treated with prednisone, compared with five of 16 participants randomised to no treatment, had improved neuropathy impairment scores after 12 weeks; the risk ratio (RR) for improvement was 2.02 (95% confidence interval (CI) 0.90 to 4.52). Adverse events were not reported in detail, but one prednisone-treated participant died.In a double-blind RCT comparing daily standard-dose oral prednisolone with monthly high-dose oral dexamethasone in 40 participants, none of the outcomes for this review were available. There were no significant differences in remission (RR 1.11; 95% CI 0.50 to 2.45 in favour of monthly dexamethasone) or change in disability or impairment after one year. Eight of 16 in the prednisolone, and seven of 24 in the dexamethasone group deteriorated. Adverse events were similar with each regimen, except that sleeplessness and moon facies (moon-shaped appearance of the face) were significantly less common with monthly dexamethasone.Experience from large non-randomised studies suggests that corticosteroids are beneficial, but long-term use causes serious side effects. AUTHORS' CONCLUSIONS: Very low quality evidence from one small, randomised trial did not show a statistically significant benefit from oral prednisone compared with no treatment. Nevertheless, corticosteroids are commonly used in practice. According to moderate quality evidence from one RCT, the efficacy of high-dose monthly oral dexamethasone was not statistically different from that of daily standard-dose oral prednisolone. Most adverse events occurred with similar frequencies in both groups, but sleeplessness and moon facies were significantly less common with monthly dexamethasone. Further research is needed to identify factors which predict response.