Undiagnosed obstructive sleep apnea syndrome as a treatable cause of new-onset sleepiness in some post-COVID patients.

BACKGROUND AND PURPOSE: Infection with COVID-19 can lead to persistent sequelae, such as fatigue, daytime sleepiness or disturbed sleep, that can remain for more than 12 weeks and that are summarized as post-COVID syndrome. The causes remain unclear. The present study investigated the presence of sleep disorders in patients with post-COVID syndrome using polysomnography. METHODS: Thirty-four patients with post-COVID syndrome and new-onset fatigue and sleepiness after a SARS-CoV2 infection underwent polysomnography in accordance with American Association of Sleep Medicine (AASM) standards as part of their clinical workup. Analysis was performed visually based on AASM criteria (scoring manual version 2.6, 2020). RESULTS: Polysomnography revealed a sleep efficiency of <80% in 50% of patients and a mean respiratory disturbance index (RDI) of 9.9 ± 15.4/h. Excluding central apneas, 12 patients (35%) had an RDI of ≥5/h, pointing to obstructive sleep apnea syndrome (OSAS; AASM 2014). Patients with a high RDI were significantly older (p = 0.01) and showed a trend towards a higher body mass index (p = 0.08) than patients with a normal RDI but had no other risk factors for OSAS. Six patients agreed to long-term treatment of their OSAS and all reported discontinuation of daytime symptoms. CONCLUSIONS: Post-COVID symptoms such as daytime sleepiness, fatigue and memory and concentration problems may in part be a result of reduced sleep efficiency and sleep apnea in a relevant percentage of patients. This possibly treatable cause of the symptoms should be kept in mind in patients presenting with post-COVID syndrome.

First epileptic seizure and quality of life - A prospective study.

OBJECTIVE: Impaired QoL and depression are common in patients with chronic epilepsies; however, data on the impact of a first seizure on QoL are sparse. According to the current ILAE-definition of epilepsy, patients may be diagnosed with epilepsy immediately after the first seizure, if EEG and/or imaging findings are abnormal. Patients with normal findings in imaging and EEG are not diagnosed as having epilepsy. We investigated QoL in patients after a first seizure with and without a consecutive diagnosis of epilepsy to detect differences between groups within the first year after seizure. METHODS: We examined patients (n = 152) after a first epileptic seizure and six and 12 months thereafter using demographic, clinical and QoL-related questionnaire data (Short Form-36 Health Survey (SF-36), Quality of Life in Epilepsy Inventory-31 (QOLIE-31), Beck's depression inventory II (BDI-II)). RESULTS: Patients diagnosed with epilepsy after the first seizure showed a tendency of reduced mental health-related QoL six (p =.098) and 12 months (p =.092) after the first seizure compared to patients who were not diagnosed with epilepsy, but were diagnosed as having had a single first seizure. There were no significant differences between the two groups in physical health-related QoL. Multiple regression analyses showed that especially depressive symptoms explained 22.0 - 48.7 % of the variance in mental health-related QoL six (p <.001) and 12 months (p <.001) after the first seizure. Physical health-related QoL was especially predicted by age (p <.001), group (p =.002) and recurrent seizures (p = < 0.001). In PWE, there was a statistical trend with improving QOLIE-31 overall scores from six to 12 months (p =.086). CONCLUSION: Our results suggest that QoL may be impaired in patients diagnosed with epilepsy early, immediately after the onset of disease. Early follow-up monitoring from the beginning of patient career is important for possible interventions and to improve patients' daily life in the long term.

Diffusion magnetic resonance imaging connectome features are predictive of functional lateralization of semantic processing in the anterior temporal lobes.

Assessment of regional language lateralization is crucial in many scenarios, but not all populations are suited for its evaluation via task-functional magnetic resonance imaging (fMRI). In this study, the utility of structural connectome features for the classification of language lateralization in the anterior temporal lobes (ATLs) was investigated. Laterality indices for semantic processing in the ATL were computed from task-fMRI in 1038 subjects from the Human Connectome Project who were labeled as stronger rightward lateralized (RL) or stronger leftward to bilaterally lateralized (LL) in a data-driven approach. Data of unrelated subjects (n = 432) were used for further analyses. Structural connectomes were generated from diffusion-MRI tractography, and graph theoretical metrics (node degree, betweenness centrality) were computed. A neural network (NN) and a random forest (RF) classifier were trained on these metrics to classify subjects as RL or LL. After classification, comparisons of network measures were conducted via permutation testing. Degree-based classifiers produced significant above-chance predictions both during cross-validation (NN: AUC-ROC[CI] = 0.68[0.64-0.73], accuracy[CI] = 68.34%[63-73.2%]; RF: AUC-ROC[CI] = 0.7[0.66-0.73], accuracy[CI] = 64.81%[60.9-68.5]) and testing (NN: AUC-ROC[CI] = 0.69[0.53-0.84], accuracy[CI] = 68.09[53.2-80.9]; RF: AUC-ROC[CI] = 0.68[0.53-0.84], accuracy[CI] = 68.09[55.3-80.9]). Comparison of network metrics revealed small effects of increased node degree within the right posterior middle temporal gyrus (pMTG) in subjects with RL, while degree was decreased in the right posterior cingulate cortex (PCC). Above-chance predictions of functional language lateralization in the ATL are possible based on diffusion-MRI connectomes alone. Increased degree within the right pMTG as a right-sided homologue of a known semantic hub, and decreased hubness of the right PCC may form a structural basis for rightward-lateralized semantic processing.

Perception of memory performance after first seizure in patients with and without an epilepsy diagnosis.

OBJECTIVES: Memory complaints in patients with epilepsy have been well-studied. Although memory complaints are commonly reported by patients with chronic epilepsy, to date, few studies exist on memory complaints at the onset of epilepsy. The present study investigated the presence of memory complaints and their relation to mood and memory performance in patients after their first seizure. Thereby, we examined differences between individuals who received a diagnosis of epilepsy immediately with the occurrence of their first seizure and those who were diagnosed as having the first epileptic seizure, without fulfilling the ILAE criteria for the diagnosis of epilepsy. METHODS: Sixty-one patients participated in the study and completed, among others, a memory task and questionnaires on memory complaints and depression after their first epileptic seizure. We investigated the level of memory complaints and their correlation and accuracy in classification with a memory measure. We compared patients who received an epilepsy diagnosis after the first seizure with those who did not. RESULTS: Memory complaints did not correlate with objective memory performance. Classification into impaired/unimpaired showed low concordance between memory complaints and neuropsychological memory measures. After their first epileptic seizure, patients reported few memory complaints overall (10%), and there were no differences in memory complaints between patients with and without an epilepsy diagnosis. CONCLUSION: At epilepsy onset, in contrast to established epilepsies, memory complaints are rare. Although influences of anticonvulsant drugs and seizures are not present at the beginning of epilepsy, this substantial absence of memory complaints at epilepsy onset emphasizes the need for comprehensive neurological and psychological treatment early with the given diagnosis. Treatment should focus on anticonvulsant drug regimens, patients' concerns and convey realistic expectations.

Examination of the Flynn effect in German patients with epilepsy assessed with the Wechsler Adult Intelligence Scale (WAIS) III and IV.

The Flynn effect describes an increase in intelligence quotient (IQ) in the general population of about 3 points per decade. While this effect is well established in healthy individuals, research exploring the link to brain pathologies is scarce. We investigated the Flynn effect in a German sample of 203 patients with epilepsy with left, right, and bilateral lesions. Intelligence quotient values were obtained using the Wechsler Adult Intelligence Scales (WAIS) III and IV. Our results showed a stable Flynn effect with nearly no difference in adjusted full scale IQ (FSIQ) scores (0.02 IQ points) between the WAIS-III and WAIS-IV samples. There were no significant interactions between the side of pathology and corrected IQ values. Our sample showed a tendency towards performing worse in the WAIS-IV in three out of four subscales independently of the Flynn effect, pointing out methodological differences between the newer Wechsler editions. However, although patients with bilateral lesions performed worst across all subscales, they exhibited a similar pattern as patients with lesions in the left or right hemisphere, indicating that also more severe forms of brain pathologies can profit from the mechanisms behind the Flynn effect.

Morphometric correlates in patients with functional seizures with and without comorbid epilepsy.

OBJECTIVE: Functional seizures (FS) or psychogenic, non-epileptic seizures (PNES) are episodic alterations of behaviour with similar semiology to epileptic seizures but which are not caused by epileptic brain activity. Epilepsy patients show a high risk in developing FS; therefore, the purpose of this study is to examine morphometric correlates in patients with FS as well as in epilepsy patients with FS by comparing them separately to healthy controls (HC). METHODS: Twenty-one clinical three-dimensional (3D) T1-magnetic resonance imaging (MRI) scans of patients with FS (FS group) and 15 patients with FS and epilepsy (EFS group) were retrospectively compared with one control group of 21 age- and gender-matched HC. Two separate general linear model analyses were conducted via FreeSurfer version 6.0. RESULTS: The study population consisted of 21 FS patients (66.7% females, n = 14) with a median age at the time of the scan of 24 years (range 17-44 years); 15 EFS patients (80% females, n = 12) with a median age at the time of the scan of 27 years (range 16-43 years); and 21 healthy subjects (66.7% females, n = 14) with a median age at the time of the scan of 24 years (range 19-38 years). Both patient groups showed an increased Cth in the right prefrontal lobe: in the FS group in the right superior frontal, rostral middle frontal gyri and the right orbitofrontal cortex and, in the EFS group, in the right superior frontal gyrus and the right orbitofrontal cortex. Decreases in Cth were present in the right lateral occipital lobe in the FS group, while also in both hemispheres in the EFS group, namely the left paracentral, superior frontal, caudal middle frontal, lateral occipital and right superior frontal gyri. Neither group showed changes in curvature. CONCLUSION: These results suggest alterations in regions of emotional processing and executive control in patients with FS regardless of the presence of epilepsy.

Determinants of quality of life in adults with epilepsy: a multicenter, cross-sectional study from Germany.

BACKGROUND: Assessment of quality of life (QoL) has become an important indicator for chronic neurological diseases. While these conditions often limit personal independence and autonomy, they are also associated with treatment-related problems and reduced life expectancy. Epilepsy has a tremendous impact on the QoL of patients and their families, which is often underestimated by practitioners. The aim of this work was to identify relevant factors affecting QoL in adults with epilepsy. METHODS: This cross-sectional, multicenter study was conducted at four specialized epilepsy centers in Germany. Patients diagnosed with epilepsy completed a standardized questionnaire focusing on QoL and aspects of healthcare in epilepsy. Univariate regression analyses and pairwise comparisons were performed to identify variables of decreased QoL represented by the overall Quality of Life in Epilepsy Inventory (QOLIE-31) score. The variables were then considered in a multivariate regression analysis after multicollinearity analysis. RESULTS: Complete datasets for the QOLIE-31 were available for 476 patients (279 [58.6%] female, 197 [41.4%] male, mean age 40.3 years [range 18-83 years]). Multivariate regression analysis revealed significant associations between low QoL and a high score on the Liverpool Adverse Events Profile (LAEP; beta=-0.28, p < 0.001), Hospital Anxiety and Depression Scale - depression subscale (HADS-D; beta=-0.27, p < 0.001), Neurological Disorders Depression Inventory in Epilepsy (NDDI-E; beta=-0.19, p < 0.001), revised Epilepsy Stigma Scale (beta=-0.09, p = 0.027), or Seizure Worry Scale (beta=-0.18, p < 0.001) and high seizure frequency (beta = 0.14, p < 0.001). CONCLUSION: Epilepsy patients had reduced QoL, with a variety of associated factors. In addition to disease severity, as measured by seizure frequency, the patient's tolerability of anti-seizure medications and the presence of depression, stigma, and worry about new seizures were strongly associated with poor QoL. Diagnosed comorbid depression was underrepresented in the cohort; therefore, therapeutic decisions should always consider individual psychobehavioral and disease-specific aspects. Signs of drug-related adverse events, depression, fear, or stigmatization should be actively sought to ensure that patients receive personalized and optimized treatment. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00022024; Universal Trial Number: U1111-1252-5331).

Validation of automatic MRI hippocampal subfield segmentation by histopathological evaluation in patients with temporal lobe epilepsy.

OBJECTIVE: The present study validates the results of automated hippocampal subfield segmentation with histopathology in epilepsy patients undergoing epilepsy surgery. METHODS: We performed an automated hippocampal subfield segmentation on presurgical three-dimensional, T1-weighted magnetization Prepared Rapid Acquisition of Gradient Echoes Magnetic Resonance Imaging (MRI) data of 25 patients with unilateral mesial temporal lobe epilepsy due to hippocampal sclerosis (HS), using Freesurfer Version 6.0. The resulting volumes of cornu ammonis (CA) subfields CA1, CA2/3, CA4 and the dentate gyrus (DG) were compared to the histopathological cell count. RESULTS: We found a significant correlation between histopathology in subregion CA2 and automated segmentation of subregion CA1 (p = 0.0062), CA2/3 (p = 0.004), CA4 (p = 0.0062) and the DG (p = 0.0054), between histopathology in CA3 and automated segmentation of CA1 (p = 0.0132), CA2/3 (p = 0.0004), CA4 (p = 0.0032) and the DG (p = 0.0037), as well as between histopathology in the DG and automated segmentation of CA1 (p = 0.0115), CA2/3 (p < 0.0001), CA4 (p < 0.0001) and the DG (p = 0.0001). The histopathological finding of HS type 1 could correctly be classified in all cases on MRI. SIGNIFICANCE: The present study shows significant correlations between histopathological evaluation and results of the automated segmentation of the hippocampus, thereby validating the automated segmentation method. As the differential involvement of different hippocampal subfields may be associated with clinical parameters and the outcome after epilepsy surgery, the automated segmentation is also promising for prognostic purposes.

Transcutaneous auricular vagus nerve stimulation influences gastric motility: A randomized, double-blind trial in healthy individuals.

BACKGROUND: Transcutaneous auricular vagus nerve stimulation (taVNS) has been investigated regarding its therapeutic properties in several several conditions such as epilepsy, migraine and major depressive disorder and was shown to access similar neural pathways as invasive vagus nerve stimulation. While the vagus nerve's role in gut motility is physiologically established, the effect of taVNS has scarcely been investigated in humans and yielded conflicting results. Real-time gastric magnetic resonance imaging (rtMRI) is an established reproducible method to investigate gastric motility non-invasively. OBJECTIVE: To investigate the influence of taVNS on gastric motility of healthy participants using rtMRI. METHODS: We conducted a randomized, double-blind study using high-frequency (HF) stimulation at 25Hz or low-frequency (LF) taVNS at 1Hz after ingestions of a standardized meal in 57 healthy participants. The gastric motility index (GMI) was determined by measuring the amplitude and velocity of the peristaltic waves using rtMRI. RESULTS: After HF taVNS, GMI was significantly higher than after LF stimulation (p = 0.005), which was mainly attributable to a higher amplitude of the peristaltic waves (p = 0.003). CONCLUSION: We provide evidence that 4-h of taVNS influences gastric motility in healthy human participants for the first time using rtMRI. HF stimulation is associated with higher amplitudes of peristaltic waves in the gastric antrum compared to LF stimulation. Further studies are needed to investigate the effect of different frequencies of taVNS and its therapeutic properties in conditions with impaired gastric motility.

First clinical postmarketing experiences in the treatment of epilepsies with brivaracetam: a retrospective observational multicentre study.

OBJECTIVES: Brivaracetam (BRV) is the latest approved antiepileptic drug and acts as a synaptic vesicle protein 2A ligand. The aim of the present study was to evaluate the efficacy and tolerability of BRV in the clinical setting. DESIGN: Retrospective, observational multicentre study. SETTING: We retrospectively collected clinical data of patients who received BRV in 10 epilepsy centres using a questionnaire that was answered by the reporting neurologist. PARTICIPANTS: Data of 615 epilepsy patients treated with BRV were included in the study. PRIMARY AND SECONDARY OUTCOME MEASURES: Efficacy regarding seizure frequency and tolerability of BRV were evaluated. Descriptive statistics complemented by X2 contingency tests and effect sizes were performed. RESULTS: Overall, 44% of the patients had a decreased, 38% a stable and 18% an increased seizure frequency. 17% of patients achieved seizure freedom after initiation of BRV. The seizure frequency decreased in 63% of 19 patients with BRV monotherapy. 27% reported adverse effects, but only 10% of patients with monotherapy. Brivaracetam was significantly more often associated with decreased seizure frequency in levetiracetam (LEV) naïve patients (p=0.012), but BRV also led to a decreased seizure frequency in 42% of patients who had been treated with LEV before, including 17% of patients who were completely seizure free. Adverse effects under LEV improved in 62% and deteriorated in 2% of patients after the switch to BRV. At latest follow-up (mean±SD = 26.3±6.5 months), 68% were still on BRV. CONCLUSIONS: The present study shows that results of the phase III studies on BRV match data from real life clinical settings. Brivaracetam seems to be a useful alternative in patients who have suffered adverse effects while taking LEV.

Brivaracetam in the Treatment of Patients with Epilepsy-First Clinical Experiences.

OBJECTIVES: To assess first clinical experiences with brivaracetam (BRV) in the treatment of epilepsies. METHODS: Data on patients treated with BRV from February to December 2016 and with at least one clinical follow-up were collected from electronic patient records. Data on safety and efficacy were evaluated retrospectively. RESULTS: In total, 93 patients were analyzed; 12 (12.9%) received BRV in monotherapy. The mean duration to follow-up was 4.85 months (MD = 4 months; SD = 3.63). Fifty-seven patients had more than one seizure per month at baseline and had a follow-up of more than 4 weeks; the rate of ≥50% responders was 35.1% (n = 20) in this group, of which five (8.8%) patients were newly seizure-free. In 50.5% (47/93), patients were switched from levetiracetam (LEV) to BRV, of which 43 (46.2%) were switched immediately. Adverse events (AE) occurred in 39.8%, with 22.6% experiencing behavioral and 25.8% experiencing non-behavioral AE. LEV-related AE (LEV-AE) were significantly reduced by switching to BRV. The discontinuation of BRV was reported in 26/93 patients (28%); 10 of those were switched back to LEV with an observed reduction of AE in 70%. For clinical reasons, 12 patients received BRV in monotherapy, 75% were seizure-free, and previous LEV-AE improved in 6/9 patients. BRV-related AE occurred in 5/12 cases, and five patients discontinued BRV. CONCLUSION: BRV seems to be a safe, easy, and effective option in the treatment of patients with epilepsy, especially in the treatment of patients who have psychiatric comorbidities and might not be good candidates for LEV treatment. BRV broadens the therapeutic spectrum and facilitates personalized treatment.