Permanent loss of independence in adult febrile-infection-related epilepsy syndrome survivors: an underestimated and unsolved challenge.

BACKGROUND AND PURPOSE: Febrile-infection-related epilepsy syndrome (FIRES) is an exceedingly rare and devastating subtype of new-onset refractory status epilepticus, which causes refractory epilepsy and permanent neurocognitive impairment. METHODS: This was a long-term follow-up of adult FIRES survivors treated between 2005 and 2018 as part of the EpiCARE initiative, a European Reference Network for rare and complex epilepsies. Clinical, electroencephalography, imaging and functional outcome measures are described using the Scores of Independence for Neurologic and Geriatric Rehabilitation, the modified Rankin Scale and the Global Assessment of Severity of Epilepsy Scale. RESULTS: Six patients with refractory epilepsy following FIRES were evaluated. Despite general improvement after intensive care unit discharge, disease severity was still high at follow-up in all patients. The functional outcome, as assessed by the modified Rankin Scale, was moderately impaired in 2/6 patients. In contrast, the Scores of Independence for Neurologic and Geriatric Rehabilitation indicated a loss of independence in 5/6, serious problems in memory and planning/problem-solving in 4/6 and serious attentional problems in 3/6 patients. CONCLUSIONS: Febrile-infection-related epilepsy syndrome survivors may regain vital functions and mobility but experience a significant loss of independence and participation due to recurring seizures, structural brain damage and neurocognitive decline. Minimization of disastrous outcomes through the systematic evaluation of rescue therapies within a network of specialized centres is crucial.

Can commercially available wearable EEG devices be used for diagnostic purposes? An explorative pilot study.

Electroencephalography (EEG) is a core element in the diagnosis of epilepsy syndromes and can help to monitor antiseizure treatment. Mobile EEG (mEEG) devices are increasingly available on the consumer market and may offer easier access to EEG recordings especially in rural or resource-poor areas. The usefulness of consumer-grade devices for clinical purposes is still underinvestigated. Here, we compared EEG traces of a commercially available mEEG device (Emotiv EPOC) to a simultaneously recorded clinical video EEG (vEEG). Twenty-two adult patients (11 female, mean age 40.2 years) undergoing noninvasive vEEG monitoring for clinical purposes were prospectively enrolled. The EEG recordings were evaluated by 10 independent raters with unmodifiable view settings. The individual evaluations were compared with respect to the presence of abnormal EEG findings (regional slowing, epileptiform potentials, seizure pattern). Video EEG yielded a sensitivity of 56% and specificity of 88% for abnormal EEG findings, whereas mEEG reached 39% and 85%, respectively. Interrater reliability coefficients were better in vEEG as compared to mEEG (ϰ = 0.50 vs. 0.30), corresponding to a moderate and fair agreement. Intrarater reliability between mEEG and vEEG evaluations of simultaneous recordings of a given participant was moderate (ϰ = 0.48). Given the limitations of our exploratory pilot study, our results suggest that vEEG is superior to mEEG, but that mEEG can be helpful for diagnostic purposes. We present the first quantitative comparison of simultaneously acquired clinical and mobile consumer-grade EEG for a clinical use-case.

Serum biomarkers of cerebral cellular stress after self-limiting tonic clonic seizures: An exploratory study.

OBJECTIVE: It has been debated for decades whether single, self-limited seizures damage cerebral cells. Meanwhile, very sensitive measurements of biomarkers have become available, i.e. tau, neurofilament protein light (NFL), glial fibrillary acidic protein (GFAP) and ubiquitin carboxyterminate hydrolase L1 (UCHL-1), which we explored in this study. METHODS: Adult patients of the epilepsy monitoring unit were admitted to the study after written consent. Blood samples were drawn at baseline, immediately after a TCS and after two, six and 24 h. The markers were measured from frozen samples with a single-molecule array (SIMOA). RESULTS: 20 patients and 20 seizures were included. All markers showed subtle but significant postictal increases and returned to normal within the next few hours (p < 0.05). An increase of at least 100 % from baseline was noted in 30 % of patients for tau, 25 % for UCHL-1 and 15 % for GFAP, while NFL levels never increased above 100 %. Lactate was slightly correlated with the tau increase (r = 0.47, p = 0.037), leukocytes were correlated with postictal changes of GFAP (r = 0.68 p = 0.001). CONCLUSION: Our data supports the assumption that significant cerebral stress occurs in some but not all self-limited TCS. The postictal inflammatory response in particular seems to play an important role.

CSF and Serum Biomarkers of Cerebral Damage in Autoimmune Epilepsy.

Introduction: Our goal was to investigate whether biomarkers of cerebral damage are found in autoimmune-mediated epilepsy (AIE) and whether these can differentiate AIE from other seizure disorders. Methods: We retrospectively searched our cerebrospinal fluid (CSF) database for patients with definite AIE, hippocampal sclerosis due to other causes (HS), genetic generalized epilepsy (GGE), and psychogenic, non-epileptic seizures (PNES). We measured serum and CSF tau, neurofilament 1 (NFL), glial fibrillary acid protein (GFAP), and ubiquitin-carboxy-terminal hydrolase L1 with a single-molecule array. Results: We identified suitable samples from patients with AIE (n = 13) with different antibodies and compared them to HS (n = 13), GGE (n = 7), and PNES (n = 8). The NFL levels were significantly elevated in the serum (p = 0.0009) and CSF (p < 0.0019) of AIE patients. The AIE group was significantly older, while the disease duration was significantly shorter than in the control groups. NFL correlated significantly with age in all groups, and the NFL levels of AIE patients were hardly higher than those of healthy elderly people published elsewhere. Conclusions: Our data indicate that the elevated NFL levels in AIE patients are most likely due to the higher age in this group and not due to the underlying inflammation. Unless larger prospective studies with intra-individual, longitudinal analyses and treatment responses would contradict our findings, NFL in serum might yet become a biomarker for disease activity and differential diagnosis.

Prevention of sudden unexpected death in epilepsy: current status and future perspectives.

Introduction: Sudden unexpected death in epilepsy (SUDEP) affects about 1 in 1000 people with epilepsy, and even more in medically refractory epilepsy. As most people are between 20 and 40 years when dying suddenly, SUDEP leads to a considerable loss of potential life years. The most important risk factors are nocturnal and tonic-clonic seizures, underscoring that supervision and effective seizure control are key elements for SUDEP prevention. The question of whether specific antiepileptic drugs are linked to SUDEP is still controversially discussed. Knowledge and education about SUDEP among health-care professionals, patients, and relatives are of outstanding importance for preventive measures to be taken, but still poor and widely neglected.Areas covered: This article reviews epidemiology, pathophysiology, risk factors, assessment of individual SUDEP risk and available measures for SUDEP prevention. Literature search was done using Medline and Pubmed in October 2019.Expert opinion: Significant advances in the understanding of SUDEP were made in the last decade which allow testing of novel strategies to prevent SUDEP. Promising current strategies target neuronal mechanisms of brain stem dysfunction, cardiac susceptibility for fatal arrhythmias, and reliable detection of tonic-clonic seizures using mobile health technologies.Abbreviations: AED, antiepileptic drug; CBZ, carbamazepine; cLQTS, congenital long QT syndrome; EMU, epilepsy monitoring unit; FBTCS, focal to bilateral tonic-clonic seizures; GTCS, generalized tonic-clonic seizures; ICA, ictal central apnea; LTG, lamotrigine; PCCA, postconvulsive central apnea; PGES, postictal generalized EEG suppression; SRI, serotonin reuptake inhibitor; SUDEP, sudden unexpected death in epilepsy; TCS, tonic-clonic seizures.

Rare mutations of CACNB2 found in autism spectrum disease-affected families alter calcium channel function.

Autism Spectrum Disorders (ASD) are complex neurodevelopmental diseases clinically defined by dysfunction of social interaction. Dysregulation of cellular calcium homeostasis might be involved in ASD pathogenesis, and genes coding for the L-type calcium channel subunits CaV1.2 (CACNA1C) and CaVß2 (CACNB2) were recently identified as risk loci for psychiatric diseases. Here, we present three rare missense mutations of CACNB2 (G167S, S197F, and F240L) found in ASD-affected families, two of them described here for the first time (G167S and F240L). All these mutations affect highly conserved regions while being absent in a sample of ethnically matched controls. We suggest the mutations to be of physiological relevance since they modulate whole-cell Ba2+ currents through calcium channels when expressed in a recombinant system (HEK-293 cells). Two mutations displayed significantly decelerated time-dependent inactivation as well as increased sensitivity of voltage-dependent inactivation. In contrast, the third mutation (F240L) showed significantly accelerated time-dependent inactivation. By altering the kinetic parameters, the mutations are reminiscent of the CACNA1C mutation causing Timothy Syndrome, a Mendelian disease presenting with ASD. In conclusion, the results of our first-time biophysical characterization of these three rare CACNB2 missense mutations identified in ASD patients support the hypothesis that calcium channel dysfunction may contribute to autism.

Actigraphic evidence for night-time hyperkinesia in Parkinson's disease.

Parkinson's disease is a common motor disorder that not only leads to motor symptoms but also autonomic dysregulation, mental changes, sensory disturbances, and sleep disorders such as increased daytime sleepiness and sleep fragmentation. The aim of this study was to find out how the daytime and night-time motor activity levels in individuals without motor disorders differ from patients with Parkinson's disease. Daytime and night-time motor activity levels in 17 PD patients and 69 controls were measured for three consecutive days and nights via actigraphy, a method of continuous long-term assessment of activity levels. A ratio between night-time and daytime motor activity was calculated. PD patients had a 1.5-2-fold lower daytime motor activity but also showed 1.5-2-fold higher motor activity at night time. Older controls showed a lower daytime but similar night-time motor activity when compared to younger controls. A ratio of night-time to daytime motor activity could clearly distinguish controls and patients. The possibility to distinguish patients and controls by the ratio of night-time to daytime motor activity is worth further investigation.