Reduced REM sleep: a potential biomarker for epilepsy - a retrospective case-control study.

OBJECTIVE: Establishing the diagnosis of epilepsy can be challenging if interictal epileptic discharges (IEDs) or seizures are undetectable. Many individuals with epilepsy experience sleep disturbances. A reduced percentage of REM sleep (REM%) has been observed following seizures. We aimed to assess differences of REM% in individuals with epilepsy in comparison with differential diagnoses. METHODS: We performed a retrospective, monocentric, two-armed case-control study with 128 age-matched individuals who underwent ≥72 hours of continuous video-EEG monitoring at our epilepsy monitoring unit (EMU) for diagnostic evaluation. We assessed REM% on the first and last night of EMU admission. Logistic regressions models were used to evaluate the predictive value of REM%. RESULTS: We included 64 individuals diagnosed with epilepsy and 64 with a differential diagnosis. REM% in the epilepsy group was significantly lower [12.2% (±4.7) vs. 17.2% (±5.2), p<0.001]. We found no significant influence of sex, age, anti-seizure, or other medications. A REM%-based and an IED and seizure-based regression model were not significantly different [area under the curve (AUC) 0.791 (95% confidence interval (CI): 0.713-0.870) vs. 0.853 (95% CI: 0.788-0.919), p=0.23]. A combined model, based on IEDs, seizures, and REM%, was superior to the IED model alone [0.933 (0.891-0.975), p<0.01]. INTERPRETATION: Our study shows significantly reduced REM% in individuals with epilepsy. REM%-based models show a good predictive performance. REM% assessment could improve diagnostic accuracy - especially for challenging cases, e.g., when IEDs or seizures are absent and patient history and semiology appear ambiguous. REM% as a biomarker should be evaluated in prospective, multicentric trials.

Long COVID-19: Objectifying most self-reported neurological symptoms.

OBJECTIVES: We aimed to objectify and compare persisting self-reported symptoms in initially hospitalized and non-hospitalized patients after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by applying clinical standardized measures. METHODS: We conducted a cross-sectional study of adult patients with confirmed SARS-CoV-2 infection including medical history, neurological examination, blood markers, neuropsychological testing, patient-reported outcome measures (PROMs), and brain magnetic resonance imaging (MRI). RESULTS: Fifty patients with persisting symptoms for at least 4 weeks were included and classified by initial hospitalization status. Median time from SARS-CoV-2 detection to investigation was 29.3 weeks (range 3.3-57.9). Although individual cognitive performance was generally within the normative range in both groups, mostly mild deficits were found in attention, executive functions, and memory. Hospitalized patients performed worse in global cognition, logical reasoning, and processes of verbal memory. In both groups, fatigue severity was associated with reduced performance in attention and psychomotor speed tasks (rs = -0.40, p < 0.05) and reduced quality of life (EQ5D, rs = 0.57, p < 0.001) and with more persisting symptoms (median 3 vs. 6, p < 0.01). PROMs identified fatigue, reduced sleep quality, and increased anxiety and depression in both groups but more pronounced in non-hospitalized patients. Brain MRI revealed microbleeds exclusively in hospitalized patients (n = 5). INTERPRETATION: Regardless of initial COVID-19 severity, an individuals' mental and physical health can be severely impaired in the long-term limitedly objectified by clinical standard diagnostic with abnormalities primarily found in hospitalized patients. This needs to be considered when planning rehabilitation therapies and should give rise to new biomarker research.

Neurological symptoms in COVID-19: a cross-sectional monocentric study of hospitalized patients.

BACKGROUND: The SARS-Coronavirus-2 (SARS-CoV-2) invades the respiratory system, causing acute and sometimes severe pulmonary symptoms, but turned out to also act multisystematically with substantial impact on the brain. A growing number of studies suggests a diverse spectrum of neurological manifestations. To investigate the spectrum of symptoms, we here describe the neurological manifestations and complications of patients with proven SARS-CoV-2 infection who have been hospitalized at the RWTH University Hospital Aachen, Germany. METHODS: Between March and September 2020, we evaluated common symptoms, clinical characteristics, laboratory (including cerebrospinal fluid (CSF) analysis), radiological, and electroencephalography (EEG) data from 53 patients admitted with a positive SARS-CoV-2 polymerase chain reaction (PCR). We used the Montreal Cognitive Assessment Test (MoCA) to screen for cognitive impairment, when feasible. We compared critically ill and non-critically ill patients categorized according to the presence of Acute Respiratory Distress Syndrome (ARDS). RESULTS: Major clinical neurological features of hospitalized COVID-19 patients were coordination deficits (74%), cognitive impairment (61.5%), paresis (47%), abnormal reflex status (45%), sensory abnormalities (45%), general muscle weakness and pain (32%), hyposmia (26%), and headache (21%). Patients with ARDS were more severely affected than non-ADRS patients. 29.6% of patients with ARDS presented with subarachnoid bleedings, and 11.1% showed ischemic stroke associated with SARS-CoV-2 infection. Cognitive deficits mainly affected executive functions, attention, language, and delayed memory recall. We obtained cerebrospinal fluid (CSF) by lumbar puncture in nine of the 53 patients, none of which had a positive SARS-CoV-2 PCR. CONCLUSIONS: In line with previous findings, our results provide evidence for a range of SARS-CoV-2-associated neurological manifestations. 26% of patients reported hyposmia, emphasizing the neuro-invasive potential of SARS-CoV-2, which can enter the olfactory bulb. It can therefore be speculated that neurological manifestations may be caused by direct invasion of the virus in the CNS; however, PCR did not reveal positive intrathecal SARS-CoV-2. Therefore, we hypothesize it is more likely that the para-infectious severe pro-inflammatory impact of COVID-19 is responsible for the neurological deficits including cognitive impairment. Future studies with comprehensive longitudinal assessment of neurological deficits are required to determine potential long-term complications of COVID-19.

Arousal thresholds during human tonic and phasic REM sleep.

The goal of the present study was to investigate arousal thresholds (ATs) in tonic and phasic episodes of rapid eye movement (REM) sleep, and to compare the frequency spectrum of these sub-states of REM to non-REM (NREM) stages of sleep. We found the two REM stages to differ with regard to behavioural responses to external acoustic stimuli. The AT in tonic REM was indifferent from that in sleep stage 2, and ATs in phasic REM were similar to those in slow-wave sleep (stage 4). NREM and REM stages of similar behavioural thresholds were distinctly different with regard to their frequency pattern. These data provide further evidence that REM sleep should not be regarded a uniform state. Regarding electroencephalogram frequency spectra, we found that the two REM stages were more similar to each other than to NREM stages with similar responsivity. Ocular activity such as ponto-geniculo-occipital-like waves and microsaccades are discussed as likely modulators of behavioural responsiveness and cortical processing of auditory information in the two REM sub-states.