Report on Electroencephalographic Findings in Critically Ill Patients with COVID-19.

In March 2020, we treated a cohort of 26 critically ill hospitalized SARS-CoV-2-infected patients who underwent electroencephalography to assess unexplained altered mental status, loss of consciousness, or poor arousal and responsiveness. Of the 26 patients studied, 5 patients had electroencephalograms that showed periodic discharges consisting of high-amplitude frontal monomorphic delta waves with absence of epileptic activity. These findings may suggest central nervous system injury potentially related to COVID-19 in these patients. ANN NEUROL 2020;88:626-630.

Correction to: COVID-19-associated acute cerebral venous thrombosis: clinical, CT, MRI and EEG features.

An amendment to this paper has been published and can be accessed via the original article.

Catching the invisible: mesial temporal source contribution to simultaneous EEG and SEEG recordings.

Mesial temporal sources are presumed to escape detection in scalp electroencephalographic recordings. This is attributed to the deep localization and infolded geometry of mesial temporal structures that leads to a cancellation of electrical potentials, and to the blurring effect of the superimposed neocortical background activity. In this study, we analyzed simultaneous scalp and intracerebral electroencephalographic recordings to delineate the contribution of mesial temporal sources to scalp electroencephalogram. Interictal intracerebral spike networks were classified in three distinct categories: solely mesial, mesial as well as neocortical, and solely neocortical. The highest and earliest intracerebral spikes generated by the leader source of each network were marked and the corresponding simultaneous intracerebral and scalp electroencephalograms were averaged and then characterized both in terms of amplitude and spatial distribution. In seven drug-resistant epileptic patients, 21 interictal intracerebral networks were identified: nine mesial, five mesial plus neocortical and seven neocortical. Averaged scalp spikes arising respectively from mesial, mesial plus neocortical and neocortical networks had a 7.1 (n = 1,949), 36.1 (n = 628) and 10 (n = 1,471) µV average amplitude. Their scalp electroencephalogram electrical field presented a negativity in the ipsilateral anterior and basal temporal electrodes in all networks and a significant positivity in the fronto-centro-parietal electrodes solely in the mesial plus neocortical and neocortical networks. Topographic consistency test proved the consistency of these different scalp electroencephalogram maps and hierarchical clustering clearly differentiated them. In our study, we have thus shown for the first time that mesial temporal sources (1) cannot be spontaneously visible (mean signal-to-noise ratio -2.1 dB) on the scalp at the single trial level and (2) contribute to scalp electroencephalogram despite their curved geometry and deep localization.

Intracerebral electrical stimulation of a face-selective area in the right inferior occipital cortex impairs individual face discrimination.

During intracerebral stimulation of the right inferior occipital cortex, a patient with refractory epilepsy was transiently impaired at discriminating two simultaneously presented photographs of unfamiliar faces. The critical electrode contact was located in the most posterior face-selective brain area of the human brain (right "occipital face area", rOFA) as shown both by low- (ERP) and high-frequency (gamma) electrophysiological responses as well as a face localizer in fMRI. At this electrode contact, periodic visual presentation of 6 different faces by second evoked a larger electrophysiological periodic response at 6 Hz than when the same face identity was repeated at the same rate. This intracerebral EEG repetition suppression effect was markedly reduced when face stimuli were presented upside-down, a manipulation that impairs individual face discrimination. These findings provide original evidence for a causal relationship between the face-selective right inferior occipital cortex and individual face discrimination, independently of long-term memory representations. More generally, they support the functional value of electrophysiological repetition suppression effects, indicating that these effects can be used as an index of a necessary neural representation of the changing stimulus property.

Right hemispheric dominance of visual phenomena evoked by intracerebral stimulation of the human visual cortex.

Electrical brain stimulation can provide important information about the functional organization of the human visual cortex. Here, we report the visual phenomena evoked by a large number (562) of intracerebral electrical stimulations performed at low-intensity with depth electrodes implanted in the occipito-parieto-temporal cortex of 22 epileptic patients. Focal electrical stimulation evoked primarily visual hallucinations with various complexities: simple (spot or blob), intermediary (geometric forms), or complex meaningful shapes (faces); visual illusions and impairments of visual recognition were more rarely observed. With the exception of the most posterior cortical sites, the probability of evoking a visual phenomenon was significantly higher in the right than the left hemisphere. Intermediary and complex hallucinations, illusions, and visual recognition impairments were almost exclusively evoked by stimulation in the right hemisphere. The probability of evoking a visual phenomenon decreased substantially from the occipital pole to the most anterior sites of the temporal lobe, and this decrease was more pronounced in the left hemisphere. The greater sensitivity of the right occipito-parieto-temporal regions to intracerebral electrical stimulation to evoke visual phenomena supports a predominant role of right hemispheric visual areas from perception to recognition of visual forms, regardless of visuospatial and attentional factors.

Electrical source imaging in cortical malformation-related epilepsy: a prospective EEG-SEEG concordance study.

OBJECTIVE: Delineation of the epileptogenic zone (EZ) in refractory epilepsy related to malformations of cortical development (MCDs) often requires intracranial electroencephalography (EEG) recordings, especially in cases of negative magnetic resonance imaging (MRI) or discordant MRI and video-EEG findings. It is therefore crucial to promote the development of noninvasive methods such as electrical source imaging (ESI). We aimed to (1) analyze the localization concordance of ESI derived from interictal discharges and EZ estimated by stereo-EEG (SEEG); (2) compare the concordance of ESI, MRI, and electroclinical correlations (ECCs) with SEEG-EZ; and (3) assess ESI added value in the EZ localization. METHODS: We prospectively analyzed 28 consecutive patients undergoing presurgical investigation for MCD-related refractory epilepsy in 2009-2012. ESI derived from 64-channel scalp EEG was interpreted with blinding to, and subsequently compared with, SEEG-estimated EZ. Anatomic concordance of ESI with SEEG-EZ was compared with that of video-EEG and MRI. We further assessed ESI added value to ECC and MRI. RESULTS: Twelve patients (43%) had temporal and 16 (57%) had extratemporal epilepsy. MRI was negative in 11 (39%) and revealed a cortical malformation in 17 (61%). ESI was fully concordant with the EZ in 10 (36%) and partly concordant in 15 (53%). ECC presented a full and partial concordance with EZ in 11% and 82% of cases, respectively, and MRI in 11% and 46%, respectively. Of 11 patients with negative MRI, ESI was fully concordant with the EZ in 7 (64%) and partly concordant in 4 (36%). ESI correctly confirmed restricted or added localizations to ECC and MRI in 12 (43%) of 28 patients and in 8 (73%) of 11 patients with negative MRI. SIGNIFICANCE: ESI contributes to estimating the EZ in MCD-related epilepsy. The added value of ESI to ECC is particularly high in patients with MCD and negative MRI, who represent the most challenging cases for epilepsy surgery. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Direct evidence of nonadherence to antiepileptic medication in refractory focal epilepsy.

The adherence to medication in drug-resistant focal epilepsy (RFE) remains largely unknown. The present work aimed to assess the frequency of recent adherence to antiepileptic drugs (AEDs) in patients with RFE. This prospective observational study screened all patients with RFE, admitted to the Nancy University Hospital between April 2006 and September 2008, for a 5-day hospitalization without AED tapering. The adherence to AEDs was assessed by measuring serum drug levels on day 1 (reflecting the recent "at home" adherence) and day 5 (reflecting the individual reference concentration when drug ingestion was supervised). A patient was considered nonadherent if at least one of their serum drug levels was different between days 1 and 5. The day-1 value was considered different from day 5 when it was at least 30% lower (underdosed) or 30% higher (overdosed). Nonadherent patients were classified as under-consumers in the case of one or more underdosed day-1 values, over-consumers in the case of one or more overdosed day-1 values, or undefined if they exhibited both underdosed and overdosed day-1 values. Forty-four of the 48 screened patients were included. Eighteen (40.9%) of 44 patients were nonadherent. Among them, 12 (66.7%) were over-consumers, 4 (22.2%) were under-consumers, and 2 (11.1%) were undefined nonadherents. The study indicates that recent adherence to antiepileptic medication in this group of patients with RFE is poor. Overconsumption is the most frequent form of nonadherence in this population and should be specifically assessed to prevent its possible consequences in terms of AEDs dose-dependent adverse events.

[Adherence to medication and epilepsy: a current issue]. / Adhésion au traitement médicamenteux et épilepsie : un enjeu d'actualité

As in other chronic diseases, adherence to medication in epilepsy is critical for seizure control. Its assessment remains challenging in research as in clinical practice. Recent evidences showed another face of nonadherence: the overconsumption of antiepileptic drugs. Some educational interventions with easy implementation were found to be effective in improving adherence and should be therefore more used in everyday practice.

ESPERA study: applicability of the new ILAE criteria for antiepileptic drug resistance of focal epilepsies in current clinical practice.

A European observational cross-sectional study, ESPERA, was conducted in France and Spain in 2010. A random sample of neurologists, including specialists in epilepsy, prospectively enrolled adult patients treated for focal epilepsy with at least two antiepileptic drugs (AEDs) in combination. Investigators were asked to classify AED responsiveness of each enrolled patient according to the new 2009 ILAE criteria. These classifications were then reviewed by three experts. Potential factors of misclassification were then analyzed in order to evaluate the applicability of the new ILAE criteria for antiepileptic drug resistance in current clinical practice. Because of their complexity, use of the new ILAE criteria needs to be supported by relevant information and training to be adequately applied by neurologists in everyday practice.

Seizure freedom is not adversely affected by early discontinuation of concomitant anti-epileptic drugs in the EULEV cohort of levetiracetam users.

PURPOSE: Fear of discontinuing concomitant anti-epileptic drugs (AEDs) may lead to potentially unnecessary and perhaps unsafe polypharmacy. The effect of withdrawing concomitant AEDs on epilepsy control was therefore studied in long-term users of levetiracetam. METHODS: The EULEV cohort followed patients initiating levetiracetam in France in 2005 or 2006 for one year. In those maintaining levetiracetam throughout the study period, the association of a reduction in the number of concomitant AEDs during the first six months with seizure-freedom during the last six months of follow-up was investigated using logistic regression. RESULTS: Of the 356 patients continuing levetiracetam for at least 1 year, 140 (39.3%) were seizure-free during the last six months of follow-up. Partial symptomatic or generalised idiopathic epilepsy were associated with greater seizure-freedom than partial cryptogenic disease. Factors associated with seizures were: longer disease duration, initial incapacity, increased number of seizures in the six months preceding levetiracetam initiation, and number of consultations for epilepsy in the six months preceding levetiracetam initiation. There was a trend for the association between the early reduction in the number of concomitant AEDs and seizure-free status later during follow-up, which however did not reach statistical significance in the final propensity score-adjusted multivariate model (OR = 1.8, 95%CI [0.8;4.0]). CONCLUSIONS: Taking into account the various risk factors for seizures, the early reduction of concomitant AEDs was not associated with worse seizure rates during follow-up in real-life users of levetiracetam.

Clinical classification of psychogenic non-epileptic seizures based on video-EEG analysis and automatic clustering.

BACKGROUND: Psychogenic non-epileptic seizures (PNES) or attacks consist of paroxysmal behavioural changes that resemble an epileptic seizure but are not associated with electrophysiological epileptic changes. They are caused by a psychopathological process and are primarily diagnosed on history and video-EEG. Clinical presentation comprises a wide range of symptoms and signs, which are individually neither totally specific nor sensitive, making positive diagnosis of PNES difficult. Consequently, PNES are often misdiagnosed as epilepsy. The aim of this study was to identify homogeneous groups of PNES based on specific combinations of clinical signs with a view to improving timely diagnosis. METHODS: The authors first retrospectively analysed 22 clinical signs of 145 PNES recorded by video-EEG in 52 patients and then conducted a multiple correspondence analysis and hierarchical cluster analysis. RESULTS: Five clusters of signs were identified and named according to their main clinical features: dystonic attack with primitive gestural activity (31.6%); pauci-kinetic attack with preserved responsiveness (23.4%); pseudosyncope (16.9%); hyperkinetic prolonged attack with hyperventilation and auras (11.7%); axial dystonic prolonged attack (16.4%). When several attacks were recorded in the same patient, they were automatically classified in the same subtype in 61.5% of patients. CONCLUSION: This study proposes an objective clinical classification of PNES based on automatic clustering of clinical signs observed on video-EEG. It also suggests that PNES are stereotyped in the same patient. Application of these findings could help provide an objective diagnosis of patients with PNES.

Effect of hyperventilation on seizure activation: potentiation by antiepileptic drug tapering.

OBJECTIVE: To determine prospectively the efficacy of hyperventilation (HV) to activate epileptic seizures and the contribution of antiepileptic drug tapering. METHODS: Eighty patients with proven epilepsy and referred for long-term video-EEG monitoring were consecutively enrolled from November 2007 to December 2008. A seizure was considered as 'activated' if it occurred during HV or within 5 min after completion. The rate of activated seizures (number of seizures/h) was compared with the rate of spontaneous seizure. The authors finally compared the effect of HV before and during antiepileptic drug (AED) tapering. RESULTS: The authors analysed 247 days of monitoring. Among 52 recorded seizures, 18 were activated by HV. The rate of activated seizure was nine times higher than the rate of control seizures (p=0.001). In the subgroup of patients with no AED tapering, there was no significant activating effect of HV on seizures. In the subgroup undergoing AED tapering, the effect of HV was not significant before (p=0.257) but very significant during AED tapering (p<0.004). DISCUSSION: The findings confirm that hyperventilation is efficient to activate epileptic seizures in epileptic patients referred for long-term video-EEG monitoring and that this activating effect is mainly related to the potentiating effect of AED tapering. Repeated HVs combined with AED tapering increase the rate of recorded seizures and the diagnostic yield of daytime video-EEG monitoring.

The EULEV cohort study: rates of and factors associated with continuation of levetiracetam after 1 year.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Levetiracetam has shown good safety/tolerability and efficacy in regulatory trials. This was confirmed in observational investigations performed soon after marketing by using continuation or retention rates as a composite measure. When an anti-epileptic drug first becomes available; however, there is evidence of channelling to more severe patients than thereafter. WHAT THIS STUDY ADDS: This study was performed several years after marketing of levetiracetam and found high rates of continuation. It also further explores this measure by determining the continuation in the absence of initiation of additional anti-epileptic drugs. AIMS: To investigate real-life effectiveness of levetiracetam in patients initiating treatment in a stable market situation. METHODS: Epileptic adults who had initiated levetiracetam between 1 January and 31 August in 2005 or 2006 were included and followed for 1 year by hospital or nonhospital neurologists practising in France. One-year continuation rates were estimated using Kaplan-Meier analysis. Among those still treated at end of study, treatment goals were investigated. Factors associated with discontinuation were investigated using Cox proportional hazards regression. RESULTS: A total of 794 subjects were included in the cohort, and 753 subjects were followed up and included in the analysis. Among these, mean (SD) age was 42.6 (±17.0) years, 51.1% were female, 76.6% had partial epilepsy, 93.5% had seizures in the 6 months preceding levetiracetam initiation and 82.9% had at least one concomitant anti-epileptic drug when starting levetiracetam. One-year levetiracetam continuation rate was 83.5% (95% confidence interval, 80.5-86.0%). Of the 579 patients still using levetiracetam at end of study, 46.8% were seizure free during the last 6 months, and 24% were on levetiracetam monotherapy. Reasons for discontinuation (n= 122) were adverse events (45%), lack of efficacy (38%) or both (9%). Levetiracetam discontinuation was most strongly associated with previous exposure to more than four anti-epileptic drugs, whereas continuation was most strongly associated with presence of seizure-related falls in the 6 months preceding levetiracetam initiation. CONCLUSIONS: This population-based cohort study in a stable market situation found a high 1 year levetiracetam continuation rate compared with previous studies done sooner after market introduction.

Bitemporal form of partial reading epilepsy: further evidence for an idiopathic localization-related syndrome.

Idiopathic partial reading epilepsy (RE) is a rare syndrome. We report the clinical and electroencephalographic characteristics of two right-handed patients with the following: reading-induced independent bilateral temporal lobe seizures, accompanied by alexia in left (dominant) sided seizures recorded on video-EEG (electroencephalography); subclinical activation over left posterior temporal and occipital electrodes during reading; no spontaneous seizure and no other trigger than reading; onset in adolescence; and history of varying resistance to treatment. Bilateral independent temporal lobe reflex seizures are part of the clinical spectrum of RE. It may result from hyperexcitability of bilateral cortical networks involved in the early steps of the reading process.

Posterior glucose hypometabolism in Lafora disease: early and late FDG-PET assessment.

Establishing an early diagnosis of Lafora disease (LD) is often challenging. We describe two cases of LD presenting as myoclonus and tonic-clonic seizures, initially suggesting idiopathic generalized epilepsy. The subsequent course of the disease was characterized by drug-resistant myoclonic epilepsy, cognitive decline, and visual symptoms, which oriented the diagnosis toward progressive myoclonic epilepsy and, more specifically, LD. Early in the evolution in the first case, and before histopathologic and genetic confirmation of LD in both cases, [18]Fluorodeoxyglucose positron emission tomography (FDG-PET) revealed posterior hypometabolism, consistent with the well-known posterior impairment in this disease. This suggests that FDG-PET could help to differentiate LD in early stages from other progressive myoclonic epilepsies, but confirmation is required by a longitudinal study of FDG-PET in progressive myoclonic epilepsy.

[Impact of group therapeutic education in the management of adult sleep disorders. Prospective study conducted from September 2007 to March 2008 by a group of general practitioners]. / Impact d'une démarche d'éducation thérapeutique de groupe dans la prise en charge des troubles du sommeil de l'adulte. Etude prospective réalisée de septembre 2007 a mars 2008 par un groupe de médecins généralistes.

UNLABELLED: The prescription of hypnotic drugs in the management of adult insomnia is a public health issue. The implementation of a non-pharmacological, therapeutic approach is a daily problem for primary physicians. OBJECTIVE: This study aimed at assessing the impact of a group therapeutic education approach in the non-medical management of adult insomnia by general practitioners. METHOD: Prospective study conducted from September 2007 to March 2008. Two conferences were held in a two-month period by 5 general practitioners from Laxou, Meurthe-et-Moselle (France). Volunteers were recruited by general practitioners, through local press, posters displayed in pharmacies, leaflet distribution and local radio announcements. A questionnaire was provided at the beginning and the end of the conferences. A phone interview was conducted 1 month and 3 months after the conferences were held, to assess their impact. RESULTS: Seventy-six participants completed the questionnaire during both conferences, and 55 adults were followed-up at 1 and 3 months; 58% (n = 43) were aged over 60, and women represented 65% (n = 48) of the participants; 63% (n = 46) reported insomnia, out of which 89% complained of chronic insomnia (26%, 40% and 34% reported mild insomnia, moderate insomnia and severe insomnia, respectively). At 3 months, 20% of the participants had completed the sleep diary and specifically seen their general practitioner; 56% of the participants taking hypnotic drugs had initiated a dose reduction or a discontinuation of their treatment; 84% of the participants who followed recommendations and initiated cognitive behavioral therapies noted a partial or complete improvement in their sleep disorder. CONCLUSION: Group therapeutic education in the form of cognitive behavioral therapy performed during a conference results in a change in behaviors and a mid-term improvement in sleep quality in participants.

Herpes simplex encephalitis: A new type of "ICU-acquired infection"?

PURPOSE: Although it is a well-known disease, the occurrence of Herpes simplex encephalitis (HSE) during a hospital stay may render the diagnosis particularly challenging. The objective of this report is to alert clinicians about the diagnostic pitfalls arising from hospital-developed HSE. MATERIALS AND METHODS: Clinical observation of one patient. CASE REPORT: An 87-year-old male was admitted to the Intensive Care Unit (ICU) because of respiratory failure due to an exacerbation of myasthenia gravis. After corticoids and azathioprine treatment, his clinical condition improved, allowing weaning from mechanical ventilation. One month after admission, while still hospitalized in the ICU, the patient developed fever and confusion. In the context of confounding factors, HSE was not suspected before a convulsive status epilepticus occurred, resulting in a significant delay in treatment. Diagnosis was confirmed by PCR-analysis in the cerebrospinal fluid. Serological status confirmed reactivation of prior herpes simplex infection. The patient died one week after the onset of confusion. CONCLUSIONS: Hospital-"acquired" HSE must be suspected in case of new neurologic symptoms associated with fever, even in ICU-hospitalized patients. The diagnosis is made even more difficult by nonspecific symptoms due to previous diseases, leading to an even more severe prognosis in those vulnerable patients.

Reference values of aortic pulse wave velocity in the elderly.

BACKGROUND: Increased aortic pulse wave velocity (AoPWV) is an independent predictor of cardiovascular morbidity and mortality. There are, however, no generally accepted limits for defining the normal or reference values. The aim of the present study was to define reference values for AoPWV. PATIENTS AND METHODS: AoPWV was assessed using applanation tonometry (PulsePen device) in a community living ambulatory population of 455 individuals aged 60-75 years. AoPWV was studied in a group of 206 individuals without hypertension or diabetes, called the 'reference-values group' (RVG), and in a group of 249 individuals with hypertension or diabetes, called the hypertension-diabetes group (HDG). The 95th percentile of the samples was used to determine the upper limit of AoPWV reference values. RESULTS: Mean AoPWV was 8.7+/-2.3 m/s in the RVG and 10.2+/-2.5 m/s in the hypertension-diabetes group (P<0.0001). In the RVG, median AoPWV in the three age subgroups was 8.0 m/s (7.6-8.5) in the 60-64-, 8.0 m/s (7.5-9.0) in the 65-69- and 9.0 m/s (7.9-9.5) in the 70-75-year-old group (NS among groups). In the entire RVG, the upper bounds of the 75th and the 95th percentile of the sample's AoPWV were 10 and 13 m/s, respectively, with no difference between sexes. CONCLUSION: In elderly individuals of 60-75 years, an AoPWV value below 10 m/s, measured with the PulsePen device, can be considered as a normal value. Values of 10-13 m/s can be considered as 'high normal' or 'borderline', whereas an AoPWV above 13 m/s is frankly elevated. This study provides, for the first time in the elderly, reference values of AoPWV.