Prospective Cohort Study

Secret History: Return of the Black Death Channel 4, 7-8pm In 1348 the Black Death swept through London, killing people within days of the appearance of their first symptoms. Exactly how many died, and why, has long been a mystery. This Secret History documentary follows experts as they pick through the evidence and reveal why the plague killed on such a scale. And they ask, what might be coming next?

Medscape

The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

Integrative analysis of 111 reference human epigenomes

Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

BACKGROUND: More than 30 percent of patients with epilepsy have inadequate control of seizures with drug therapy, but why this happens and whether it can be predicted are unknown. We studied the response to antiepileptic drugs in patients with newly diagnosed epilepsy to identify factors associated with subsequent poor control of seizures. METHODS: We prospectively studied 525 patients (age, 9 to 93 years) who were given a diagnosis, treated, and followed up at a single center between 1984 and 1997. Epilepsy was classified as idiopathic (with a presumed genetic basis), symptomatic (resulting from a structural abnormality), or cryptogenic (resulting from an unknown underlying cause). Patients were considered to be seizure-free if they had not had any seizures for at least one year. RESULTS: Among the 525 patients, 333 (63 percent) remained seizure-free during antiepileptic-drug treatment or after treatment was stopped. The prevalence of persistent seizures was higher in patients with symptomatic or cryptogenic epilepsy than in those with idiopathic epilepsy (40 percent vs. 26 percent, P=0.004) and in patients who had had more than 20 seizures before starting treatment than in those who had had fewer (51 percent vs. 29 percent, P<0.001). The seizure-free rate was similar in patients who were treated with a single established drug (67 percent) and patients who were treated with a single new drug (69 percent). Among 470 previously untreated patients, 222 (47 percent) became seizure-free during treatment with their first antiepileptic drug and 67 (14 percent) became seizure-free during treatment with a second or third drug. In 12 patients (3 percent) epilepsy was controlled by treatment with two drugs. Among patients who had no response to the first drug, the percentage who subsequently became seizure-free was smaller (11 percent) when treatment failure was due to lack of efficacy than when it was due to intolerable side effects (41 percent) or an idiosyncratic reaction (55 percent). CONCLUSIONS: Patients who have many seizures before therapy or who have an inadequate response to initial treatment with antiepileptic drugs are likely to have refractory epilepsy.

Early Identification of Refractory Epilepsy

PURPOSE OF THE REVIEW: Malaria, Chagas Disease and Human African Trypanosomiasis are vector-borne protozoan illnesses, frequently associated with neurological manifestations. Intriguing but ignored, limited mainly to resource-limited, tropical settings, these disorders are now coming to light because of globalisation and improved diagnosis and treatment. Enhanced understanding of these illnesses has prompted this review. RECENT FINDINGS: Methods of diagnosis have currently transitioned from blood smear examinations to immunological assays and molecular methods. Tools to assess neurological involvement, such as magnetic resonance imaging, are now increasingly available in regions and countries with high infection loads. Sleep and other electrophysiological technologies (electroencephalography, actigraphy) are also promising diagnostic tools but requiring field-validation. Access to treatments was formerly limited, even as limitations of agents used in the treatment are increasingly recognised. Newer agents are now being developed and trialled, encouraged by improved understanding of the disorders' molecular underpinnings. SUMMARY: Prompt diagnosis and treatment are crucial in ensuring cure from the infections. Attention should also be due to the development of globally applicable treatment guidelines, the burden of neurological sequelae and elimination of the zoonoses from currently endemic regions.

Vector-borne protozoal infections of the CNS: cerebral malaria, sleeping sickness and Chagas disease

A 61-year-old woman, who lived alone, presented with severe problems with her sleep pattern. She had a history of cryptogenic partial epilepsy since she was 8 years old. Her epilepsy consisted of complex partial seizures, starting with vocalisation, followed by unresponsiveness and oro-alimentary automatisms. For 38 years she had taken phenytoin (300 mg/day) on which she had suffered no daytime seizures but one or two nocturnal seizures per year. At age 50 years she developed right foot numbness, which progressed over a few months to both feet and both legs. Following investigation she was diagnosed with a peripheral neuropathy secondary to long term phenytoin. She was therefore converted first to sodium valproate (on which she had daytime complex partial seizures, weight gain and bruising) and then to carbamazepine (which was stopped due to slurred speech). The patient decided to restart phenytoin, despite the neuropathy. At age 55 years she fractured both ankles; a dual energy x-ray absorptiometry scan revealed osteopaenia, probably due to long term phenytoin. She started alendronic acid and calcium, and lamotrigine was gradually substituted—increasing up to 150 mg daily—for the phenytoin. After this she developed sleep complaints, mood instability and extreme daytime tiredness. She reported only one nocturnal seizure while on lamotrigine but after she had her first ever daytime generalised tonic—clonic seizure it was stopped and phenytoin restarted, increasing to 200 mg daily; the sleep disturbance settled.

At age 57 years the patient was referred to our epilepsy clinic. She had been on phenytoin for over 45 years. A 24 h ambulatory electroencephalogram (EEG) revealed left temporal interictal epileptiform discharges and one nocturnal seizure with left hemisphere EEG onset. MR brain scan showed focal …

https://pn.bmj.com/content/practneurol/10/4/233.full.pdf

A fitful night's sleep.

http://www.epilepsybehavior.com/article/S1525505022003171/pdf

Josemir W. Sander

Papers

Vector-borne protozoal infections of the CNS: cerebral malaria, sleeping sickness and Chagas disease

A fitful night's sleep.

Retention of brivaracetam in adults with drug-resistant epilepsy at a single tertiary care center

Antiepileptic Drugs in Clinical Trials

Tropical spastic paraparesis.