Staged treatment response in status epilepticus: Lessons from the SENSE registry.

OBJECTIVES: Although in epilepsy patients the likelihood of becoming seizure-free decreases substantially with each unsuccessful treatment, to our knowledge this has been poorly investigated in status epilepticus (SE). We aimed to evaluate the proportion of SE cessation and functional outcome after successive treatment steps. METHODS: We conducted a post hoc analysis of a prospective, observational, multicenter cohort (Sustained Effort Network for treatment of Status Epilepticus [SENSE]), in which 1049 incident adult SE episodes were prospectively recorded at nine European centers. We analyzed 996 SE episodes without coma induction before the third treatment step. Rates of SE cessation, mortality (in ongoing SE or after SE control), and favorable functional outcome (assessed with modified Rankin scale) were evaluated after each step. RESULTS: SE was treated successfully in 838 patients (84.1%), 147 (14.8%) had a fatal outcome (36% of them died while still in SE), and 11 patients were transferred to palliative care while still in SE. Patients were treated with a median of three treatment steps (range 1-13), with 540 (54.2%) receiving more than two steps (refractory SE [RSE]) and 95 (9.5%) more than five steps. SE was controlled after the first two steps in 45%, with an additional 21% treated after the third, and 14% after the fourth step. Likelihood of SE cessation (p < 0.001), survival (p = 0.003), and reaching good functional outcome (p < 0.001) decreased significantly between the first two treatment lines and the third, especially in patients not experiencing generalized convulsive SE, but remained relatively stable afterwards. SIGNIFICANCE: The significant worsening of SE prognosis after the second step clinically supports the concept of RSE. However, and differing from findings in human epilepsy, RSE remains treatable in about one third of patients, even after several failed treatment steps. Clinical judgment remains essential to determine the aggressiveness and duration of SE treatment, and to avoid premature treatment cessation in patients with SE.

[Neurology: what's new in 2023]. / Neurologie: ce qui a changé en 2023.

The year 2023 is marked by the arrival on the market of lecanemab for the treatment of Alzheimer's disease. New biomarkers have demonstrated their usefulness in monitoring peripheral neuropathies and diagnosing synucleinopathies. A genetic study has highlighted the role of nervous system cells in the risk of progression of multiple sclerosis (MS). The adverse effects of anticonvulsant treatments after prenatal exposure and on lipid metabolism have been clarified. New anti-CGRP treatments have demonstrated their efficacy in migraine attacks and chronic migraines. The criteria for thrombectomy have been further broadened. And finally, rehabilitation is refining the management of cerebrovascular patients and those with secondary progressive MS.

L'année 2023 est marquée par l'arrivée sur le marché du lécanémab pour le traitement de la maladie d'Alzheimer. De nouveaux biomarqueurs ont démontré leur utilité dans le suivi des neuropathies périphériques ou dans le diagnostic des synucléinopathies. Une étude génétique a mis en évidence le rôle des cellules du système nerveux dans le risque de progression de la sclérose en plaques (SEP). Les effets indésirables des traitements anticonvulsivants lors d'exposition prénatale ou sur le métabolisme des lipides ont été précisés. De nouveaux traitements anti-CGRP ont démontré leur efficacité dans les crises migraineuses et les migraines chroniques. Les critères de thrombectomie se sont encore élargis. Et enfin, la réhabilitation affine la prise en charge des patients cérébrovasculaires et de ceux atteints d'une SEP secondaire progressive.

Multimodal Prediction of Favorable Outcome After Cardiac Arrest: A Cohort Study.

OBJECTIVES: Prognostic guidelines after cardiac arrest (CA) focus on unfavorable outcome prediction; favorable outcome prognostication received less attention. Our aim was to identify favorable outcome predictors and combine them into a multimodal model. DESIGN: Retrospective analysis of prospectively collected data (January 2016 to June 2021). SETTING: Two academic hospitals (Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Brigham and Women's Hospital, Boston, MA). PATIENTS: Four hundred ninety-nine consecutive comatose adults admitted after CA. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: CA variables (initial rhythm, time to return of spontaneous circulation), clinical examination (Full Outline of UnResponsiveness [FOUR] score at 72 hr, early myoclonus), electroencephalography (EEG) (reactivity, continuity, epileptiform features, and prespecified highly malignant patterns), somatosensory-evoked potentials, quantified pupillometry, and serum neuron-specific enolase (NSE) were retrieved. Neurologic outcome was assessed at 3 months using Cerebral Performance Category (CPC); 1 and 2 were considered as favorable outcome. Predictive performance of each variable toward favorable outcomes were calculated, and most discriminant items were combined to obtain a multimodal prognostic score, using multivariable ordinal logistic regression, receiving operator characteristic curves, and cross-validation. Our analysis identified a prognostic score including six modalities (1 point each): 1) early (12-36 hr) EEG not highly malignant, 2) early EEG background reactivity, 3) late (36-72 hr) EEG background reactivity and 4) continuity, 5) peak serum NSE within 48 hours less than or equal to 41 µg/L, and 6) FOUR score greater than or equal to 5 at 72 hours. At greater than or equal to 4 out of 6 points, sensitivity for CPC 1-2 was 97.5% (95% CI, 92.9-99.5%) and accuracy was 77.5% (95% CI, 72.7-81.8%); area under the curve was 0.88 (95% CI, 0.85-0.91). The score showed similar performances in the validation cohort. CONCLUSIONS: This study describes and externally validates a multimodal score, including clinical, EEG and biological items available within 72 hours, showing a high performance in identifying early comatose CA survivors who will reach functional independence at 3 months.

Status epilepticus prognosis following levetiracetam administration: Analysis of loading doses.

BACKGROUND AND PURPOSE: Recommended loading doses of levetiracetam (LEV) for status epilepticus (SE) treatment have increased over time. However, this was not evidence-based, and the benefit of the increase remains unclear. The effect of different LEV loading doses on SE prognosis was explored. METHODS: This is a retrospective analysis of an SE adult registry (January 2016-December 2021), including patients receiving LEV as a second-line SE treatment. Patients were stratified according to LEV loading doses (threshold 35 mg/kg). Main outcomes were global mortality, LEV use as last SE treatment, and return to baseline conditions at discharge, exploring LEV as a dichotomized or continuous dose. RESULTS: Among 202 patients, 44 received LEV at ≥35 mg/kg and 158 below it. Global mortality, adjusted for SE severity and potentially fatal aetiology, was more frequent in the high LEV dose group (27.2% vs. 17.1%, odds ratio 3.14, 95% confidence interval 1.23-8.06; p = 0.017), whilst LEV prescription as last treatment and return to baseline conditions were comparable. Considering continuous LEV dosages or mortality in ongoing SE, however, no outcome reached statistical significance. CONCLUSIONS: Lower LEV loading doses do not seem to correlate with worse clinical outcome, challenging current guidelines. Further studies, ideally prospective, are needed on this topic.

[Neurology: what's new in 2022]. / Neurologie : ce qui a changé en 2022.

The year 2022 was marked by the development of numerous new treatments for refractory myasthenia gravis. The link between epilepsy and cerebrovascular disorder was studied and lamotrigine discovered to be the optimal treatment choice for epilepsy secondary to stroke to prevent mortality on patient of 45 years and older. New randomized study finally demonstrated the utility of thrombectomy in selected patients with basilar artery occlusion. The causal relationship between Epstein-Barr infection and multiple sclerosis has been proved thanks to a large cohort study. A new possibility of subcutaneous continuous levodopa administration gave promising result. Finally, numerous studies confirmed the efficacy and excellent tolerability of anti-CGRP antibodies.

L'année 2022 a été marquée par l'arrivée de nombreux traitements pour la myasthénie réfractaire. Le lien entre l'épilepsie et le risque cérébro-vasculaire a été bien étudié, démontrant que la lamotrigine semble être le meilleur traitement pour prévenir la mortalité chez les patients de 45 ans et plus. De nouvelles études ont enfin pu établir l'utilité de la thrombectomie dans les occlusions basilaires. Le lien entre le virus d'Epstein-Barr et la sclérose en plaques a pu être prouvé à la suite d'une importante étude de cohorte. Une nouvelle technique d'administration sous-cutanée de la lévodopa semble prometteuse. Enfin, de nombreuses études confirment l'efficacité et l'excellente tolérance des anticorps anti-CGRP (Calcitonine Gene Related Protein).

Continuous Versus Routine Standardized Electroencephalogram for Outcome Prediction in Critically Ill Adults: Analysis From a Randomized Trial.

OBJECTIVES: To investigate electroencephalogram (EEG) features' relation with mortality or functional outcome after disorder of consciousness, stratifying patients between continuous EEG and routine EEG. DESIGN: Retrospective analysis of data from a randomized controlled trial. SETTING: Multiple adult ICUs. PATIENTS: Data from 364 adults with acute disorder of consciousness, randomized to continuous EEG (30-48 hr; n = 182) or repeated 20-minute routine electroencephalogram (n = 182). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Correlations between electrographic features and mortality and modified Rankin scale at 6 months (good 0-2) were assessed. Background continuity, higher frequency, and reactivity correlated with survival and good modified Rankin scale. Rhythmic and periodic patterns carried dual prognostic information: lateralized periodic discharges were associated with mortality and bad modified Rankin scale. Generalized rhythmic delta activity correlated with survival, good modified Rankin scale, and lower occurrence of status epilepticus. Presence of sleep-spindles and continuous EEG background was associated with good outcome in the continuous EEG subgroup. In the routine EEG group, a model combining background frequency, continuity, reactivity, sleep-spindles, and lateralized periodic discharges was associated with mortality at 70.91% (95% CI, 59.62-80.10%) positive predictive value and 63.93% (95% CI, 58.67-68.89%) negative predictive value. In the continuous EEG group, a model combining background continuity, reactivity, generalized rhythmic delta activity, and lateralized periodic discharges was associated with mortality at 84.62% (95%CI, 75.02-90.97) positive predictive value and 74.77% (95% CI, 68.50-80.16) negative predictive value. CONCLUSIONS: Standardized EEG interpretation provides reliable prognostic information. Continuous EEG provides more information than routine EEG.

Valproate in status epilepticus: Correlation between loading dose, serum levels, and clinical response.

BACKGROUND AND PURPOSE: Intravenous valproate (VPA) is an established treatment of status epilepticus (SE), but optimal loading dose was not fully assessed. We aimed at analyzing the correlation between VPA loading dose and subsequent plasma levels with clinical response in SE. METHODS: This was a retrospective study in one referral center of all consecutive VPA-naïve SE episodes treated with VPA between January 2013 and June 2019, in which total VPA trough plasma levels after intravenous loading dose were available. Response to VPA, defined as last antiseizure medication introduced before SE resolution (without the need for additional treatment), was correlated with VPA loading dose and trough level. Correlations were adjusted for other SE characteristics. RESULTS: Among 128 SE episodes, 53 (41%) responded to VPA. Median VPA loading dose was 25.2 mg/kg (range, 7-58 mg/kg). Loading doses and total plasma levels were not associated with the probability of response or mortality. Correcting for other possible confounders (number of previously tried treatment, demographics, SE severity) did not alter these findings. Only 3.8% of SE episodes that responded to VPA received >30 mg/kg. CONCLUSIONS: A high loading dose (>30 mg/kg) is not associated with a greater response rate in patients with SE. Therefore, it seems to bring little benefit. If confirmed in further studies, a dosage of 25-30 mg/kg appears adequate in SE.

Ketamine in adult super-refractory status epilepticus: Efficacy analysis on a prospective registry.

BACKGROUND: Status epilepticus (SE) persisting despite two anti-seizures medications (ASM) and anesthetics is labeled super refractory (SRSE), correlating with important morbidity and mortality. Its treatment relies on expert opinions. Due to its pharmacological properties, ketamine (KET) has received increasing attention, but data are essentially retrospective. AIMS: To describe an unselected cohort of adults receiving KET for SRSE. METHODS: Analysis of a prospective registry of consecutive SE episodes, identifying SRSE patients receiving ketamine (KET). Comparison with recent adult series including more than 10 patients. RESULTS: Eleven patients received KET after a median of 4 days (range: 2-20); median dose was 5 mg/kg/h (range: 2.5-15). KET provided permanent SE control in three (27%). Previous series, using KET administration delays and doses similar to our cohort, report KET efficacy in 28-96% of cases. CONCLUSIONS: We found a lower SE control rate than existing literature, whose data are, however, often retrospective, potentially selecting patients with less severe SE forms or responding to KET. This might explain outcome differences, as KET administration modalities were comparable with our cohort. Since randomized controlled studies are lacking on this subject, the analysis of this prospective, unselected cohort, if confirmed, suggests a current overestimation of KET efficacy in SRSE.

Treatment-emergent adverse events and antiseizure medication actual drug load.

OBJECTIVE: The correlation between treatment-emergent adverse events (TEAE) and antiseizure medication (ASM) drug load is a controversial topic. Previous studies used daily defined dosage (DDD) to measure drug load. We aim to assess if ASM adjusted to body weight and plasma levels were associated with TEAE. METHODS: We analyzed clinical visits of a trial on therapeutic drug monitoring in outpatients with epilepsy. TEAE, treatment, and its changes, as well as ASM plasma levels, were recorded at each visit. Each medication level was stratified according to its position in relation to its proposed reference range (below, in the lower half, upper half, or above). RESULTS: We analyzed 424 visits (151 participants). Treatment-emergent adverse events were reported in 84 (20%) visits. There was no significant difference when comparing visits with TEAE with those without TEAE in terms of ASM drug load (calculated with DDD), corrected for body weight, their changes since the last visit, as well as summed plasma levels compared to reference ranges. SIGNIFICANCE: Actual drug load seems not to represent a major determinant of TEAE recorded during routine visits, even when accounting thoroughly for the patient's exposure to the treatment. The use of structured questionnaires and neuropsychometric tests may assess more accurately the potential consequences of drug loads.

Neuroprognostication Under ECMO After Cardiac Arrest: Are Classical Tools Still Performant?

BACKGROUND: According to international guidelines, neuroprognostication in comatose patients after cardiac arrest (CA) is performed using a multimodal approach. However, patients undergoing extracorporeal membrane oxygenation (ECMO) may have longer pharmacological sedation and show alteration in biological markers, potentially challenging prognostication. Here, we aimed to assess whether routinely used predictors of poor neurological outcome also exert an acceptable performance in patients undergoing ECMO after CA. METHODS: This observational retrospective study of our registry includes consecutive comatose adults after CA. Patients deceased within 36 h and not undergoing prognostic tests were excluded. Veno-arterial ECMO was initiated in patients < 80 years old presenting a refractory CA, with a no flow < 5 min and a low flow ≤ 60 min on admission. Neuroprognostication test performance (including pupillary reflex, electroencephalogram, somatosensory-evoked potentials, neuron-specific enolase) toward mortality and poor functional outcome (Cerebral Performance Categories [CPC] score 3-5) was compared between patients undergoing ECMO and those without ECMO. RESULTS: We analyzed 397 patients without ECMO and 50 undergoing ECMO. The median age was 65 (interquartile range 54-74), and 69.8% of patients were men. Most had a cardiac etiology (67.6%); 52% of the patients had a shockable rhythm, and the median time to return of an effective circulation was 20 (interquartile range 10-28) minutes. Compared with those without ECMO, patients receiving ECMO had worse functional outcome (74% with CPC scores 3-5 vs. 59%, p = 0.040) and a nonsignificant higher mortality (60% vs. 47%, p = 0.080). Apart from the neuron-specific enolase level (higher in patients with ECMO, p < 0.001), the presence of prognostic items (pupillary reflex, electroencephalogram background and reactivity, somatosensory-evoked potentials, and myoclonus) related to unfavorable outcome (CPC score 3-5) in both groups was similar, as was the prevalence of at least any two such items concomitantly. The specificity of each these variables toward poor outcome was between 92 and 100% in both groups, and of the combination of at least two items, it was 99.3% in patients without ECMO and 100% in those with ECMO. The predictive performance (receiver operating characteristic curve) of their combination toward poor outcome was 0.822 (patients without ECMO) and 0.681 (patients with ECMO) (p = 0.134). CONCLUSIONS: Pending a prospective assessment on a larger cohort, in comatose patients after CA, the performance of prognostic factors seems comparable in patients with ECMO and those without ECMO. In particular, the combination of at least two poor outcome criteria appears valid across these two groups.

[Neurology : what's new in 2021]. / Neurologie.

In 2021, we assisted to the publication of new diagnostic criteria, classifications, and guidelines (CIDP, brain tumors, auto-immune encephalitis). Several studies helped to define the pharmacological management of focal and generalized epileptic seizures and epilepsy in pregnant women. The availability of biomarkers and the approval of immunotherapies are modifying the landscape of dementia management. Endovascular interventions without previous thrombolysis seems to be effective in anterior circulation acute ischemic stroke (AIS) and severe posterior circulation AIS. Neurologic complications of Sars-CoV-2 infection were further studied, as well as the efficacy of vaccines in immunosuppressed patients. New molecules and techniques show promising results for the treatment of migraine and cluster headache.

L'année 2021 a été marquée par la publication des nouveaux critères diagnostiques, classifications et guidelines (polyradiculonévrite inflammatoire démyélinisante chronique, tumeurs cérébrales, encéphalites autoimmunes). L'attitude thérapeutique dans les épilepsies focales ou généralisées et l'épilepsie chez la femme enceinte a été mieux définie. Les marqueurs biologiques et les immunothérapies modifient le paysage de la prise en charge des démences. Le traitement endovasculaire des AVC de la circulation antérieure semble efficace indépendamment d'une thrombolyse préalable, ainsi qu'en cas d'AVC sévère de la circulation postérieure. Les complications neurologiques du SARS-CoV-2 ont été éclaircies et l'efficacité des vaccins étudiée chez les patients immunosupprimés. Plusieurs nouvelles molécules et techniques montrent des résultats prometteurs pour les migraines et céphalées en grappe.

Therapeutic Drug Monitoring of Newer Antiepileptic Drugs: A Randomized Trial for Dosage Adjustment.

OBJECTIVE: Therapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) is widely established for older generation AEDs, whereas there is limited evidence about newer AEDs. Our aim is to assess the benefit of TDM of newer generation AEDs in epilepsy. METHODS: We performed a randomized, controlled trial comparing systematic with rescue TDM of lamotrigine, levetiracetam, oxcarbazepine, topiramate, brivaracetam, zonisamide, or pregabalin. Participants were adults with epilepsy, in whom treatment with newer generation AEDs was initiated or needed adjustment. In the systematic TDM arm, AED plasma levels were available at each appointment, whereas in the rescue TDM arm, levels were known only if a study endpoint was reached (inefficacy or adverse events). The primary outcome was the proportion of participants followed 1 year without reaching one of the predefined endpoints. RESULTS: A total of 151 participants were enrolled; global retention in the study was similar in both arms (56% overall, 58% in the systematic, and 53% in the rescue TDM arm, p = 0.6, Cox regression). There was no difference in terms of outcome regarding treatment efficacy or tolerability. Partial adherence of clinicians to TDM (adjusting or not AED dosage based on blood levels) did not explain this lack of benefit. INTERPRETATION: This study provides class A evidence that systematic drug level monitoring of newer generation AEDs does not bring tangible benefits in the management of patients with epilepsy. Poor correlation between clinical effects and drug levels likely accounts for this finding. However, TDM is useful in several situations, such as pregnancy, as well as when there are compliance issues. ANN NEUROL 2020;87:22-29.

EEG spindles integrity in critical care adults. Analysis of a randomized trial.

OBJECTIVES: Occurrence of EEG spindles has been recently associated with favorable outcome in ICU patients. Available data mostly rely on relatively small patients' samples, particular etiologies, and limited variables ascertainment. We aimed to expand previous findings on a larger dataset, to identify clinical and EEG patterns correlated with spindle occurrence, and explore its prognostic implications. METHODS: Retrospective observational study of prospectively collected data from a randomized trial (CERTA, NCT03129438) assessing the relationship of continuous (cEEG) versus repeated routine EEG (rEEG) with outcome in adults with acute consciousness impairment. Spindles were prospectively assessed visually as 12-16Hz activity on fronto-central midline regions, at any time during EEG interventions. Uni- and multivariable analyses explored correlations between spindles occurrence, clinical and EEG variables, and outcome (modified Rankin Scale, mRS; mortality) at 6 months. RESULTS: Among the analyzed 364 patients, spindles were independently associated with EEG background reactivity (OR 13.2, 95% CI: 3.11-56.26), and cEEG recording (OR 4.35, 95% CI: 2.5 - 7.69). In the cEEG subgroup (n=182), 33.5% had spindles. They had better FOUR scores (p=0.004), fewer seizures or status epilepticus (p=0.02), and lower mRS (p=0.02). Mortality was reduced (p=0.002), and independently inversely associated with spindle occurrence (OR 0.50, CI 95% 0.25-0.99) and increased EEG background continuity (OR 0.16, 95% CI: 0.07 - 0.41). CONCLUSIONS: Besides confirming that spindle activity occurs in up to one third of acutely ill patients and is associated with better outcome, this study shows that cEEG has a higher yield than rEEG in identifying them. Furthermore, it unravels associations with several clinical and EEG features in this clinical setting.

Seizure freedom and plasma levels of newer generation antiseizure medications.

OBJECTIVES: Contrary to older antiseizure medications (ASM), correlation between plasma levels and seizure freedom is not well defined for newer generation ASM. We assessed correlations between efficacy and newer generation ASM plasma levels in patients with epilepsy. MATERIALS AND METHODS: Plasma medication levels were measured over two years in consecutive patients taking lamotrigine, levetiracetam, oxcarbazepine, topiramate, zonisamide, lacosamide, perampanel or pregabalin. Seizure freedom was defined as three times the longest inter-seizure pre-treatment interval, or at least one year. Each medication level was stratified according to its position in relation to its proposed reference range (below or in lower half vs upper half or above). RESULTS: 168 patients on stable therapy were included. ASM plasma levels of seizure-free patients were lower than those with ongoing seizures; 45/48 (93.7%) were in the lower half or below the reference ranges, compared to 86/106 (81.1%; p = .004). Lamotrigine plasma levels were significantly lower in seizure-free patients (median 2.4 mg/L range 0.4-6.5 mg/L, none above 6.5 mg/L) compared with those with ongoing seizures (5 mg/L, 0.5-14.2 mg/L; p < .0001). Levetiracetam showed similar results (7.2 mg/L, 1.6-15.1 mg/L; none above 15.1 mg/L in seizure-free patients vs 16.4 mg/L, 0.6-47.7 mg/L; p = .005). Demographics, epilepsy type and polytherapy did not influence the results. CONCLUSIONS: Efficacy of newer generation ASMs seems to be reached at the lower part or at times even below the reference ranges in drug responsive patients; this could inform regarding titrations of these treatments.

[Recent Advances in Neurology]. / Neurologie.

Significant developments were published in 2020 in the field of blood biomarkers in Alzheimer's disease. Several studies helped to define more accurately the management of status epilepticus and of epilepsy in women of childbearing age. The new Swiss guidelines for the pre-hospital management of acute stroke were issued, as are new targets for stroke prevention. Numerous advances concerning the management of NMO-SD (NeuroMyelitis Optica Spectrum Disorder) were published. Different neurological presentations linked to the COVID-19 pandemic were described (central and peripheral). Several studies confirmed the effectiveness of new migraine treatments (including anti-CGRP). New pharmacological therapies are available for Parkinson's disease.

L'année 2020 a vu d'importantes avancées dans le domaine des biomarqueurs sanguins pour le diagnostic biologique de la maladie d'Alzheimer. Plusieurs études permettent de mieux définir la prise en charge de l'épilepsie chez la femme en âge de procréer et de l'état de mal épileptique. Les nouvelles recommandations suisses pour la prise en charge préhospitalière de l'AVC aigu sont en cours de publication, tout comme de nouvelles cibles pour leur prévention secondaire. De nombreuses avancées concernant la prise en charge des Neuromyelitis Optica Spectrum Disorder ont été publiées. Divers tableaux neurologiques (centraux et périphériques) liés à la pandémie de Covid-19 ont été décrits. Plusieurs études ont permis de confirmer l'efficacité des nouveaux traitements de la migraine (notamment les anti-Calcitonin Gene-Related Peptide). Enfin, de nouvelles thérapies pharmacologiques sont disponibles pour la maladie de Parkinson.

EEG patterns associated with present cortical SSEP after cardiac arrest.

BACKGROUND: After cardiac arrest (CA), present cortical somatosensory evoked potentials (N20 response of SSEPs) have low predictive value for good outcome and might be redundant with EEG. AIMS: To determine whether specific features, or rather global, standardized EEG assessments, are reliably associated with cortical SSEP occurrence after cardiac arrest (CA). METHODS: In a prospective CA registry, EEGs recorded within 72 hours were scored according to the ACNS nomenclature, and also categorized into "benign," "malignant," and "highly malignant." Correlations between EEGs and SSEPs (bilaterally absent vs present), and between EEGs/SSEPs and outcome (good: CPC 1-2) were assessed. RESULTS: Among 709 CA episodes, 532 had present N20 and 366 "benign EEGs." While EEG categories as well as background, epileptiform features, and reactivity differed significantly between patients with and without N20 (each P < .001), only "benign EEG" was almost universally associated with present N20: 99.5% (95%CI: 97.9%-99.9%) PPV. The combination of "benign EEG" and present N20 showed similar PPV for good outcome as "benign" EEG alone: 69.0% (95% CI: 65.2-72.4) vs 68.6% (95% CI: 64.9-72.0). CONCLUSION: Global EEG ("benign") assessment, rather than single EEG features, can reliably predict cortical SSEP occurrence. SSEP adjunction does not increase EEG prognostic performance toward good outcome. SSEP could therefore be omitted in patients with "benign EEG."

[Neurology 2019]. / Neurologie.

New studies confirm the possibility of late thrombolysis. Meta-analyses have confirmed that CGRP inhibitors are efficacious for migraines. Cladribine is a new oral treatment for relapsing-remitting multiple sclerosis. Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a new clinical entity accounting for cognitive decline in old patients. The timing of levodopa introduction has no effect on the long-term course of idiopathic Parkinson's disease. Hypophosphatemia helps distinguish between seizures and syncopes in the emergency department. A second course of intravenous immunoglobulins provides no benefit for severe Guillain Barre syndrome. Outdoor therapy improves clinical scales in patients with disorder of consciousness. Ultrasound guided lumbar puncture improves the yield of the procedure.

De nouvelles études confirment la possibilité de thrombolyse tardive. Les méta-analyses confirment l'effet bénéfique des inhibiteurs du CGRP (calcitonin gene-related peptide) pour la migraine. La cladribine est un nouveau traitement oral pour la sclérose en plaque de type poussée-rémission. L'encéphalopathie à TDP-43 à prédominance limbique est une nouvelle entité en lien avec des troubles cognitifs de la personne âgée. Le délai d'introduction de la lévodopa n'a pas d'influence sur l'évolution à long terme de la maladie de Parkinson. L'hypophosphatémie aide à différencier les crises d'épilepsie des syncopes. Une deuxième cure d'immunoglobulines n'apporte pas de bénéfice dans le traitement du syndrome de Guillain-Barré. Les patients avec troubles de l'état de conscience bénéficient des thérapies à l'air libre. L'ultrason améliore le rendement de la ponction lombaire.

A potential role of hypophosphatemia for diagnosing convulsive seizures: A case-control study.

OBJECTIVE: Transient loss of consciousness (TLOC) is a common presentation in the emergency room, where patient history can usually differentiate syncope from generalized tonic-clonic (GTC) seizures. Several serum markers, such as creatine kinase and lactate, can be helpful, especially when history is unreliable. Here, we explore a potential supporting role of electrolyte plasma levels in a case-control study. METHODS: In our electroencephalographic database, we retrospectively identified consecutive episodes of loss of consciousness in adults seen over 3 years in our hospital emergency department for a case-control study. We investigated plasma levels of several electrolytes (sodium, potassium, phosphate, calcium, magnesium) at the emergency visit, as well as demographics, diagnosis, blood-sample delay time, and history of alcohol abuse. RESULTS: Of the 126 patients identified, 75 had GTC seizures and 46 had other TLOC causes. Among electrolyte levels, only hypophosphatemia was associated with GTC seizures (median = 0.79 mmol·L-1 , range = 0.34-1.37 in GTC seizures vs 0.93 mmol·L-1 , range = 0.52-1.56, P = 0.001 in TLOC). After adjusting for blood sampling delay, alcohol abuse, and other electrolyte levels, only hypophosphatemia was associated with GTC seizures, occurring in 37 (51%) of GTC seizures and 12 (22%) of other TLOC (odds ratio = 3.5, 95% confidence interval = 1.5-8.3, P = 0.003). Hypophosphatemia < 0.6 mmol·L-1 was 93% specific and 20% sensitive for GTC seizure occurrence. In follow-ups, hypophosphatemia was transitory. SIGNIFICANCE: Transient hypophosphatemia is common after GTC seizures and could represent an additional biological marker to help differentiate GTC seizures from other TLOC, especially when history is unclear. This hypothesis needs to be tested prospectively.

[The follow-up of antiepileptic drug therapy]. / Suivi du traitement médicamenteux de l'épilepsie†: à quoi penser†?

Treatment of epilepsy with medication is a major part of the overall management of patients with epilepsy. We will discuss here three aspects of the follow-up of those patients; adverse events of treatment, assessment of response to treatment and biological follow-up. Adverse events associated with the therapy are not infrequent since they are reported by half of the patients. Since seizures occur mostly in an aleatory way, it is important to consider the duration observed in the assessment. A relative decrease of the seizure frequency must be interpreted cautiously as regression to the mean is frequent in the spontaneous fluctuations of the seizure frequency. Biologic follow-up is mostly helpful with older generation antiepileptic drugs.

Le traitement médicamenteux constitue la majeure partie de la prise en charge des patients souffrant d'épilepsie. Nous abordons trois aspects du suivi de ces patients ; les effets indésirables de la thérapie, l'évaluation de la réponse au traitement et le suivi biologique. Les effets indésirables ne sont pas rares puisque la moitié des patients en rapportent sous thérapie. Les crises survenant le plus souvent de manière aléatoire, il est important de considérer la durée d'observation pour pouvoir statuer sur l'efficacité du traitement. Il faut être prudent dans l'interprétation des changements relatifs à la fréquence des crises, car un phénomène de retour à la fréquence moyenne des crises (par rapport à une exacerbation) peut survenir de manière spontanée. Le suivi biologique est surtout nécessaire avec les médicaments d'anciennes générations.

[Driving rules†: first seizure and epilepsy]. / Règlements concernant la conduite†: première crise et épilepsie.

For patients with epilepsy, the occurrence of a traffic accident due to an epileptic seizure is a major problem. In order to reduce the risk of an accident, the Road Traffic Commission of the Swiss League against Epilepsy has issued guidelines concerning the driving ability of a vehicle in case of epilepsy. These directives were last modified in 2015. According to these directives, the waiting period differs according to the category of the vehicle concerned and the origin of the event (first crisis provoked or not provoked). At the occurrence of the first episode, an exhaustive evaluation is mandatory in order to avoid unnecessarily prolonged restrictions. These directives are available on : www.epi.ch/wp-content/uploads/flyer-Epilepsie_fuehrerschein-licence-conduire-2016.pdf.

Pour les patients souffrant d'épilepsie, la survenue d'un accident de la circulation à cause d'une crise d'épilepsie est une problématique majeure. Afin de réduire le risque d'accident, la Commission de la circulation routière de la Ligue suisse contre l'épilepsie a publié des directives concernant la capacité de conduite d'un véhicule en cas d'épilepsie. Ces directives ont été modifiées, la dernière fois, en 2015. Selon elles, la durée de carence est différente selon la catégorie du véhicule concernée et l'origine de l'événement comitial (première crise provoquée ou non provoquée). Une évaluation approfondie après la survenue du premier épisode est obligatoire afin d'éviter des restrictions inutilement prolongées. Les directives dont disponibles sur : www.epi.ch/wp-content/uploads/flyer-Epilepsie_fuehrerschein-licence-conduire-2016.pdf.