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Juvenile myoclonic epilepsy is a comparatively benign form of idiopathic generalised epilepsy. Little is known about the prevalence of difficult to treat or drug resistant patients. Among 155 consecutive patients with newly diagnosed juvenile myoclonic epilepsy evaluated between 1981 and 1998 and followed up for at least 1 year (61 men, 94 women; aged 15–70 years, mean 33 (SD 10.3); onset of juvenile myoclonic epilepsy at the age of 14.5 (SD 3.7), range 6–26; follow up 1–52 years, mean 13.5 (SD 9.9)), there were 15 pseudoresistant patients (9.7%: lack of compliance (eight), insufficient treatment (three), abnormal lifestyle (four)) and 24 patients (15.5%) who had persisting seizures despite adequate therapy and lifestyle. Clinical features associated with drug resistance were (1) the presence of psychiatric problems (58.3%v 19%; χ2 p<0.001) and (2) independently, the combination of seizure types (Fischer's exact 2 by 4, p=0.0026). Three types were present in 62.5% of resistant patients versus 23.3% in non-resistant patients (χ2, p=0.0001). None of the resistant patients had myoclonic jerks as the only seizure type or a combination of absences and myoclonic jerks. Family history of epilepsy, age at onset of seizures, sex, presence of photoparoxysmal response, results of conventional neuroimagings (CT and MRI), and delayed diagnosis were not significantly associated with drug resistance. There is thus a significant subgroup of patients with juvenile myoclonic epilepsy who pose difficult therapeutic problems, and the prevalence of resistant cases may be increased in the experience of a referral epilepsy centre.

Novel biomarkers of the risk of sudden unexpected death in epilepsy (SUDEP) are needed to better inform people with epilepsy of their individual risk and identify those at a high risk. The aim of this study was to identify such biomarkers, particularly with the exploration of seizures characteristics that have not been previously investigated, including peri-ictal peripheral oxygen saturation (SpO2) and site of seizure onset. We conducted a nested case–control study of SUDEP within a dedicated nationwide prospective cohort. Eligible participants were adults with drug-resistant focal epilepsy undergoing in-hospital seizure monitoring at 16 epilepsy monitoring units in France. Clinical data, results from presurgical investigations, and raw recordings from video EEG, electrocardiogram (ECG), and SpO2 were collected until the end of the recruitment period. The French National Directory of Natural Persons Identification was queried annually to identify deaths. SUDEP cases were adjudicated on the basis of medical records and interviews documenting the circumstances of death. Each SUDEP case was matched to four controls on the basis of study centre and date of inclusion. SUDEP risk factors were identified using LASSO-penalised conditional logistic regression. From May 18, 2010, to Aug 23, 2015, we enrolled a total of 1074 participants and followed their vital status until the end of 2018, yielding a total of 6828 patient-years of follow-up. 42 participants died during follow-up, including 18 cases of definite or probable SUDEP, resulting in a SUDEP rate of 2·64/1000 patient-years (95% CI 1·36–3·92). Four risk factors were significantly associated with the risk of SUDEP: an extratemporal epileptogenic zone (OR 37·8, 95% CI 3·21–446·2, p=0·0039), a BMI of 30 or higher (26·0, 2·0–339·6, p=0·013), male sex (12·6, 1·5–106·8, p=0·0201), and predominantly nocturnal seizures (6·0, 1·2–28·7, p=0·026). In contrast, the presence of peri-ictal SpO2 of less than 80% during focal seizures, the frequency of focal-to-bilateral tonic–clonic seizures, heart rate variability, age at epilepsy onset, number of antiseizure medications, and history of depression were not significantly associated with SUDEP. Extratemporal epilepsies involving the perisylvian region or frontal lobe appear to be associated with an increased risk of SUDEP. This finding warrants confirmation in larger cohorts and underscores the need to improve the diagnosis and surgical management of extratemporal epilepsies, which might contribute to improved SUDEP risk stratification and prevention. French Ministry of Health (Programme Hospitalier de Recherche Clinique National 2009).

La Société de réanimation de langue française et la Société française de médecine d’urgence ont décidé d’élaborer de nouvelles recommandations sur la prise en charge de l’état mal épileptique (EME) avec l’ambition de répondre le plus possible aux nombreuses questions pratiques que soulèvent les EME : diagnostic, enquête étiologique, traitement non spécifique et spécifique. Vingt-cinq experts ont analysé la littérature scientifique et formulé des recommandations selon la méthodologie GRADE. Les experts se sont accordés sur 96 recommandations. Les recommandations avec le niveau de preuve le plus fort ne concernent que l’EME tonico-clonique généralisé (EMTCG) : l’usage des benzodiazépines en première ligne (clonazépam en intraveineux direct ou midazolam en intramusculaire) est recommandé, répété 5 min après la première injection (à l’exception du midazolam) en cas de persistance clinique. En cas de persistance 5 min après cette seconde injection, il est proposé d’administrer la seconde ligne thérapeutique : valproate de sodium, (fos-)phénytoïne, phénobarbital ou lévétiracétam. La persistance avérée de convulsions 30 min après le début de l’administration du traitement de deuxième ligne signe l’EMETCG réfractaire. Il est alors proposé de recourir à un coma thérapeutique au moyen d’un agent anesthésique intraveineux de type midazolam ou propofol. Des recommandations spécifiques à l’enfant et aux autres EME sont aussi énoncées. Management of status epilepticus (SE) is subject to many difficulties: diagnosis, etiological investigation, non-specific and specific treatment. The French Society of Intensive Care and the French Society of Emergency Medicine, with the French Group for Pediatric Intensive Care and Emergencies, have developed guidelines to respond to the practical questions raised by SE management in the prehospital setting, in the emergency department and in the intensive care unit. Twenty-five experts analyzed the literature and formulated recommendations according to the Grade of Recommendation Assessment, Development and Evaluation methodology. The experts agreed on 96 recommendations. Recommendations with the strongest level of evidence concern only generalized tonic convulsive SE. In this setting, first-line use of benzodiazepines (direct intravenous clonazepam or intramuscular midazolam) was recommended, with a second injection in the case of clinical persistence of SE five minutes after the first injection. In the case of persistence of SE five minutes after this second injection, the recommendation is to administer the second-line treatment: sodium valproate, (fos)phenytoin, phenobarbital or levetiracetam. The confirmed persistence of convulsions 30 min after the beginning of the administration of this second-line treatment defines refractory SE. At this stage, a coma should be rapidly induced by means of a third-line general anesthetic (midazolam and/or propofol). Additional specific recommendations focus on children (except newborns) and on other types of SE.

Objective Evaluating the efficacy of an opioid antagonist, naloxone (NLX), to reduce the severity of post‐ictal hypoxemia and immobility after focal to bilateral tonic–clonic seizures (FBTCS). Methods ENALEPSY is a double‐blind placebo (PCB)‐controlled trial conducted in patients with focal epilepsy undergoing long‐term video‐EEG monitoring (LTM). Patients with a FBTCS during LTM were randomized 1:1 to receive intravenous NLX or PCB within the 2 min following the end of FBTCS. After database lock, a discrepancy between the allocated arm and the received treatment was detected, resulting in a 4:1 NLX:PCB ratio. To further explore the efficacy of NLX, we used historical control (HC) data collected in patients included in the REPO2MSE study whose characteristics matched those of patients randomized in ENALEPSY. The efficacy of NLX was then assessed versus PCB and versus HC. The primary endpoint was the delay between the end of the seizure and recovery of SpO2 ≥ 90%. Secondary efficacy outcomes included desaturation nadir and duration of the post‐ictal immobility. Results 33 patients contributed to the NLX group, 7 to the PCB group, and 43 to the HC group. The proportion of FBTCS type 1 or 3 was 84% in NLX, 100% in PCB, and 84% in HC. NLX did not improve the delay of recovery of SpO2 ≥ 90% or the desaturation nadir. By contrast, the duration of the post‐ictal immobility differed across groups. The time to mobility recovery within the first 5 min post‐ictal was very similar in the PCB (200.3 ± 215.8 s) and HC (194.4 ± 192.0 s) groups, and significantly shorter in the NLX group (128.9 ± 151.1 s) when compared to HC (Hazard Ratio, 1.84; 95% CI, 1.11–3.05; p = 0.021). Significance NLX did not prevent post‐ictal respiratory dysfunction but might reduce the duration of post‐ictal immobility. Confirmation of this effect and its impact on SUDEP risk will require additional studies. Plain Language Summary Release of endogenous opioids might participate in the severity of post‐ictal hypoxemia and immobility after focal to bilateral tonic–clonic seizures (FBTCS). We conducted a multicenter double‐blind randomized placebo‐controlled trial evaluating the efficacy of an opioid antagonist, naloxone (NLX), administered within 2 min following the end of FBTCS. The efficacy of NLX was further explored with a comparison with historical control. NLX did not improve the delay of recovery or the severity of post‐ictal hypoxemia. Post‐ictal immobility was significantly shorter in the NLX group when compared to historical control. The impact of these results on SUDEP prevention will require additional studies.

Management of status epilepticus (SE) is subject to many difficulties: diagnosis, etiological investigation, non-specific and specific treatment. The French Society of Intensive Care and the French Society of Emergency Medicine, with the French Group for Pediatric Intensive Care and Emergencies, have developed guidelines to respond to the practical questions raised by SE management in the prehospital setting, in the emergency department and in the intensive care unit. Twenty-five experts analyzed the literature and formulated recommendations according to the Grade of Recommendation Assessment, Development and Evaluation methodology. The experts agreed on 96 recommendations. Recommendations with the strongest level of evidence concern only generalized tonic convulsive SE. In this setting, first-line use of benzodiazepines (direct intravenous clonazepam or intramuscular midazolam) was recommended, with a second injection in the case of clinical persistence of SE five minutes after the first injection. In the case of persistence of SE five minutes after this second injection, the recommendation is to administer the second-line treatment: sodium valproate, (fos)phenytoin, phenobarbital or levetiracetam. The confirmed persistence of convulsions 30 min after the beginning of the administration of this second-line treatment defines refractory SE. At this stage, a coma should be rapidly induced by means of a third-line general anesthetic (midazolam and/or propofol). Additional specific recommendations focus on children (except newborns) and on other types of SE. La Société de réanimation de langue française et la Société française de médecine d’urgence ont décidé d’élaborer de nouvelles recommandations sur la prise en charge de l’état mal épileptique (EME) avec l’ambition de répondre le plus possible aux nombreuses questions pratiques que soulèvent les EME : diagnostic, enquête étiologique, traitement non spécifique et spécifique. Vingt-cinq experts ont analysé la littérature scientifique et formulé des recommandations selon la méthodologie GRADE. Les experts se sont accordés sur 96 recommandations. Les recommandations avec le niveau de preuve le plus fort ne concernent que l’EME tonico-clonique généralisé (EMTCG) : l’usage des benzodiazépines en première ligne (clonazépam en intraveineux direct ou midazolam en intramusculaire) est recommandé, répété 5 min après la première injection (à l’exception du midazolam) en cas de persistance clinique. En cas de persistance 5 min après cette seconde injection, il est proposé d’administrer la seconde ligne thérapeutique : valproate de sodium, (fos-)phénytoïne, phénobarbital ou lévétiracétam. La persistance avérée de convulsions 30 min après le début de l’administration du traitement de deuxième ligne signe l’EMETCG réfractaire. Il est alors proposé de recourir à un coma thérapeutique au moyen d’un agent anesthésique intraveineux de type midazolam ou propofol. Des recommandations spécifiques à l’enfant et aux autres EME sont aussi énoncées.

Objective The aim of our study was to investigate the effects of carbamazepine (CBZ) and oxcarbazepine (OXCBZ) on aminothiol levels, including homocysteine (Hcy), cysteine, and cysteinylglycine, in chronically treated patients. Methods Epileptic patients receiving CBZ or OXCBZ were recruited as part of routine clinical practice. Demographic data and concomitant medications were recorded from the patient medical file. Results Sixty patients were included in the study; 30 patients were treated with CBZ and 30 with OXCBZ. Median Hcy level was significantly higher in CBZ-treated patients (20.6 μmol/l) than in OXCBZ-treated patients (14.0 μmol/l, p  < 0.0001). No correlation was evidenced between antiepileptic drugs or metabolite levels and Hcy levels for each group. Conclusions Less change observed with OXCBZ compared with CBZ on aminothiol levels could constitute an advantage for OXCBZ treatment in patients with other factors influencing Hcy levels and/or at high risk for cardiovascular diseases.

Animal studies have revealed seasonal patterns in cerebrospinal fluid (CSF) monoamine (MA) turnover. In humans, no study had systematically assessed seasonal patterns in CSF MA turnover in a large set of healthy adults. Standardized amounts of CSF were prospectively collected from 223 healthy individuals undergoing spinal anesthesia for minor surgical procedures. The metabolites of serotonin (5-hydroxyindoleacetic acid, 5-HIAA), dopamine (homovanillic acid, HVA) and norepinephrine (3-methoxy-4-hydroxyphenylglycol, MPHG) were measured using high performance liquid chromatography (HPLC). Concentration measurements by sampling and birth dates were modeled using a non-linear quantile cosine function and locally weighted scatterplot smoothing (LOESS, span = 0.75). The cosine model showed a unimodal season of sampling 5-HIAA zenith in April and a nadir in October (p-value of the amplitude of the cosine = 0.00050), with predicted maximum (PC(max)) and minimum (PC(min)) concentrations of 173 and 108 nmol/L, respectively, implying a 60% increase from trough to peak. Season of birth showed a unimodal 5-HIAA zenith in May and a nadir in November (p = 0.00339; PC(max) = 172 and PC(min) = 126). The non-parametric LOESS showed a similar pattern to the cosine in both season of sampling and season of birth models, validating the cosine model. A final model including both sampling and birth months demonstrated that both sampling and birth seasons were independent predictors of 5-HIAA concentrations. In subjects without mental illness, 5-HT turnover shows circannual variation by season of sampling as well as season of birth, with peaks in spring and troughs in fall.

Long-term health-related quality of life (HR-QOL) of patients surviving the acute phase of purpura fulminans (PF) has not been evaluated.METHODS : This was a French multicenter exposed-unexposed cohort study enrolling patients admitted in 55 intensive care units (ICUs) for PF from 2010 to 2016. Adult patients surviving the acute phase of PF (exposed group) were matched 1:1 for age, sex, and Simplified Acute Physiology Score II with septic shock survivors (unexposed group). HR-QOL was assessed during a phone interview using the 36-Item Short-Form Health Survey (SF-36) questionnaire, the Hospital Anxiety and Depression (HAD) scale, the Impact of Event Scale-Revised (IES-R), and the activity of daily living (ADL) and instrumental ADL (IADL) scales. The primary outcome measure was the physical component summary (PCS) of the SF-36 questionnaire.RESULTS : Thirty-seven survivors of PF and 37 of septic shock were phone-interviewed at 55 (interquartile range [IQR], 35-83) months and 44 (IQR, 35-72) months, respectively, of ICU discharge (P = .23). The PCS of the SF-36 was not significantly different between exposed and unexposed patients (median, 47 [IQR, 36-53] vs 54 [IQR, 36-57]; P = .18). There was also no significant difference between groups regarding the mental component summary of the SF-36, and the HAD, IES-R, ADL and IADL scales. Among the 37 exposed patients, those who required limb amputation (n = 12/37 [32%]) exhibited lower PCS (34 [IQR, 24-38] vs 52 [IQR, 42-56]; P = .001) and IADL scores (7 [IQR, 4-8] vs 8 [IQR, 7-8]; P = .021) compared with nonamputated patients.CONCLUSIONS : Long-term HR-QOL does not differ between patients surviving PF and those surviving septic shock unrelated to PF. Amputated patients have an impaired physical HR-QOL but a preserved mental health