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Background Neurological COVID-19 disease has been reported widely, but published studies often lack information on neurological outcomes and prognostic risk factors. We aimed to describe the spectrum of neurological disease in hospitalised COVID-19 patients; characterise clinical outcomes; and investigate factors associated with a poor outcome. Methods We conducted an individual patient data (IPD) meta-analysis of hospitalised patients with neurological COVID-19 disease, using standard case definitions. We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute. We analysed features associated with poor outcome (moderate to severe disability or death, 3 to 6 on the modified Rankin Scale) using multivariable models. Results We included 83 studies (31 unpublished) providing IPD for 1979 patients with COVID-19 and acute new-onset neurological disease. Encephalopathy (978 [49%] patients) and cerebrovascular events (506 [26%]) were the most common diagnoses. Respiratory and systemic symptoms preceded neurological features in 93% of patients; one third developed neurological disease after hospital admission. A poor outcome was more common in patients with cerebrovascular events (76% [95% CI 67–82]), than encephalopathy (54% [42–65]). Intensive care use was high (38% [35–41]) overall, and also greater in the cerebrovascular patients. In the cerebrovascular, but not encephalopathic patients, risk factors for poor outcome included breathlessness on admission and elevated D-dimer. Overall, 30-day mortality was 30% [27–32]. The hazard of death was comparatively lower for patients in the WHO European region. Interpretation Neurological COVID-19 disease poses a considerable burden in terms of disease outcomes and use of hospital resources from prolonged intensive care and inpatient admission; preliminary data suggest these may differ according to WHO regions and country income levels. The different risk factors for encephalopathy and stroke suggest different disease mechanisms which may be amenable to intervention, especially in those who develop neurological symptoms after hospital admission.

Background Actigraphs are wrist-worn devices that record tri-axial accelerometry data used clinically and in research studies. The expense of research-grade actigraphs, however, limit their widespread adoption, especially in clinical settings. Tri-axial accelerometer-based consumer wearable devices have gained worldwide popularity and hold potential for a cost-effective alternative. The lack of independent validation of minute-to-minute accelerometer data with polysomnographic data or even research-grade actigraphs, as well as access to raw data has hindered the utility and acceptance of consumer-grade actigraphs. Methods Sleep clinic patients wore a consumer-grade wearable (Huami Arc) on their non-dominant wrist while undergoing an overnight polysomnography (PSG) study. The sample was split into two, 20 in a training group and 21 in a testing group. In addition to the Arc, the testing group also wore a research-grade actigraph (Philips Actiwatch Spectrum). Sleep was scored for each 60-s epoch on both devices using the Cole-Kripke algorithm. Results Based on analysis of our training group, Arc and PSG data were aligned best when a threshold of 10 units was used to examine the Arc data. Using this threshold value in our testing group, the Arc has an accuracy of 90.3%±4.3%, sleep sensitivity (or wake specificity) of 95.5%±3.5%, and sleep specificity (wake sensitivity) of 55.6%±22.7%. Compared to PSG, Actiwatch has an accuracy of 88.7%±4.5%, sleep sensitivity of 92.6%±5.2%, and sleep specificity of 60.5%±20.2%, comparable to that observed in the Arc. Conclusions An optimized sleep/wake threshold value was identified for a consumer-grade wearable Arc trained by PSG data. By applying this sleep/wake threshold value for Arc generated accelerometer data, when compared to PSG, sleep and wake estimates were adequate and comparable to those generated by a clinical-grade actigraph. As with other actigraphs, sleep specificity plateaus due to limitations in distinguishing wake without movement from sleep. Further studies are needed to evaluate the Arc’s ability to differentiate between sleep and wake using other sources of data available from the Arc, such as high resolution accelerometry and photoplethysmography.

Objectives To evaluate the effects of nonadherence to antiseizure medications (ASMs) and clinical characteristics on seizure control, we employed a prospective cohort cross-sectional study using self-reports and medical records of patients with epilepsy (PWEs). Methods Eight hundred and fifty-five PWEs taking ASMs were enrolled from fourteen collaborative outpatient clinics from January 2018 to March 2019. Questions from the Morisky Medication Adherence Scale were used as adherence self-reports. If a PWE’s questionnaire indicated that they had missed doses of their ASMs, outpatient physicians asked them directly about the details of their compliance, including the timing of intentionally or unintentionally missed doses. The association between lack of seizure control and utilization outcomes, such as missed doses, demographics, and clinical characteristics of the PWEs, were assessed by univariate and multivariate analyses. Results Multivariate analysis revealed that forgetting to take ASMs was associated with lack of seizure control and the existence of focal to bilateral tonic–clonic seizures. Dementia, younger age, use of three or more antiepileptic agents, and living in a one-person household were associated with the risk of forgetting to take ASMs. Significance For PWEs with poor drug management or a high incidence of missed doses of ASMs, efforts to improve adherence could facilitate better seizure control and decrease focal to bilateral tonic–clonic propagation.

In Parkinson's disease (PD), several studies have detected an impaired serotonin (5-HT) pathway, likely affecting both motor and non-motor domains. However, the precise impact of 5-HT impairment is far from established. Here, we have used a HPLC chromatographic method, in a homogenous cohort (n = 35) of non fluctuating, non dyskinetic PD patients, to assess the concentration of 5-HT and its metabolite 5-HIAA in peripheral cerebrospinal fluid (CSF) obtained from lumbar puncture (LP). LP was performed following three days of therapy withdrawal, in order to vanish the effects of prolonged released dopamine agonists (DA), and in absence of any serotonergic agent. The PD patient group showed a significantly reduced CSF level of both 5-HT and 5-HIAA compared to either age-matched control subjects (n = 18), or Alzheimer's disease patients (n = 20). However, no correlation emerged between 5-HT/5-HIAA concentrations and UPDRS-III (r = -0.12), disease duration (r = -0.1), age (r = -0.27) and MMSE (r = 0.11). Intriguingly, low CSF 5-HT levels did not differ for gender or for motor phenotype (in terms of non-tremor dominant subtype and tremor dominant subtype). Further, low CSF 5-HT levels did not correlate with the presence of depression, apathy or sleep disturbance. Our findings support the contention that 5-HT impairment is a cardinal feature of stable PD, probably representing a hallmark of diffuse Lewy bodies deposition in the brainstem. However, clinical relevance remains uncertain. Given these findings, an add-on therapy with serotonergic agents seems questionable in PD patients, or should be individually tailored, unless severe depression is present.