European Academy of Neurology guideline on the diagnosis of coma and other disorders of consciousness.

BACKGROUND AND PURPOSE: Patients with acquired brain injury and acute or prolonged disorders of consciousness (DoC) are challenging. Evidence to support diagnostic decisions on coma and other DoC is limited but accumulating. This guideline provides the state-of-the-art evidence regarding the diagnosis of DoC, summarizing data from bedside examination techniques, functional neuroimaging and electroencephalography (EEG). METHODS: Sixteen members of the European Academy of Neurology (EAN) Scientific Panel on Coma and Chronic Disorders of Consciousness, representing 10 European countries, reviewed the scientific evidence for the evaluation of coma and other DoC using standard bibliographic measures. Recommendations followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The guideline was endorsed by the EAN. RESULTS: Besides a comprehensive neurological examination, the following suggestions are made: probe for voluntary eye movements using a mirror; repeat clinical assessments in the subacute and chronic setting, using the Coma Recovery Scale - Revised; use the Full Outline of Unresponsiveness score instead of the Glasgow Coma Scale in the acute setting; obtain clinical standard EEG; search for sleep patterns on EEG, particularly rapid eye movement sleep and slow-wave sleep; and, whenever feasible, consider positron emission tomography, resting state functional magnetic resonance imaging (fMRI), active fMRI or EEG paradigms and quantitative analysis of high-density EEG to complement behavioral assessment in patients without command following at the bedside. CONCLUSIONS: Standardized clinical evaluation, EEG-based techniques and functional neuroimaging should be integrated for multimodal evaluation of patients with DoC. The state of consciousness should be classified according to the highest level revealed by any of these three approaches.

[Use of antiepileptic drugs during breastfeeding : What do we tell the mother?] / Antiepileptika in der Stillzeit : Wie beraten wir die Mütter?

BACKGROUND: Knowledge about the passage of various antiepileptic drugs into breast milk and its consequences for the infant is limited. Faced with this uncertainty, breastfeeding is often discouraged for these patients. The aim of this study was to comprehensively review the available data regarding antiepileptic drugs during breastfeeding, to compare these data with information provided by the summary of product characteristics (SmPCs), and to provide recommendations for the use of these drugs in breastfeeding women. MATERIAL AND METHODS: We performed a systematic literature review on breastfeeding data for 23 antiepileptic drugs. A breastfeeding compatibility score was developed and validated. The estimated score based on the literature review was compared with the estimated score based on recommendations provided by the SmPCs. RESULTS: We identified 75 articles containing exposure and safety data for 15 antiepileptic agents during breastfeeding. The comparison between the score values based on the literature review and on the SmPCs revealed a very low degree of concordance (weighted kappa: 0.08). CONCLUSION: Phenobarbital, primidone, carbamazepine, valproate and levetiracetam are probably compatible with breastfeeding. Treatment with phenytoin, ethosuximide, clonazepam, oxcarbazepine, vigabatrin, topiramate, gabapentin, pregabalin, lamotrigine and zonisamide can be authorized during breastfeeding, provided breastfed infants are carefully monitored for side effects. Since data on the use of mesuximide, clobazam, rufinamide, felbamate, lacosamide, sultiame, perampanel and retigabine are insufficient to adequately assess the risk for breastfed infants, use in breastfeeding women is in principle not recommended and should be carefully evaluated on a case by case basis. In practice, a risk-benefit analysis should be performed for each mother under antiepileptic treatment wishing to breastfeed her child, so that individual risk factors can adequately be taken into account when counseling the patient.

Extended EEG and non-convulsive status epilepticus: Benefit over routine EEG?

OBJECTIVE: EEG monitoring is increasingly used in critically ill patients, but impact on clinical outcome remains unclear. We aimed to investigate the benefit of repeated extended EEG in the prognosis of patients with non-convulsive status epilepticus (SE). MATERIALS & METHODS: We retrospectively collected 29 consecutive patients with non-convulsive SE without coma, who underwent repeated extended EEG between 2013 and 2015. We compared these patients with an historical age-matched group of 58 patients managed between 2011 and 2013 with routine EEG only. We excluded patients treated with therapeutic coma for SE treatment. Outcome at hospital discharge was categorized as return to baseline conditions, new disability, and death. RESULTS: Severity of SE was similar in the two groups, with similar proportion of potential fatal etiologies (58% in the extended EEG group vs 60%, P=.529), similar STESS scores (median was three in both groups, P=.714), and comparable acute hospitalization duration (median of 15 vs 11 days, P=.131). The extended EEG group received slightly more anti-epileptic drugs (median was three in both groups, P=.026). Distribution of the outcome categories at hospital discharge was similar (P=.129). CONCLUSIONS: Extended EEG used for the management of non-convulsive status epilepticus does not seem to improve clinical outcome, but is associated with a higher number of prescribed anti-epileptic drugs. The benefit of continuous EEG monitoring in non-convulsive SE without coma SE should be addressed through a randomized trial.

Refractory and super-refractory status epilepticus in adults: a 9-year cohort study.

OBJECTIVE: While status epilepticus (SE) persisting after two antiseizure agents is called refractory (RSE), super-refractory status epilepticus (SRSE) defines SE continuing after general anaesthesia. Its prevalence and related clinical profiles have received limited attention, and most studies were restricted to intensive care facilities. We therefore aimed at describing RSE and SRSE frequencies and identifying associated clinical variables. METHODS: Between 2006 and 2015, consecutive adult SE episodes were prospectively recorded in a registry. Occurrence of RSE and SRSE and their relationship to clinical variables of interest, including outcome, were analysed. RESULTS: Of 804 SE episodes, 268 (33.3%) were RSE and 33 (4%) SRSE. Coma induction for SE treatment occurred in 79 (9.8%) episodes. Severe consciousness impairment (OR 1.67; 95% CI 1.24-2.46; P = 0.001), increasing age (OR 1.01, 95% CI 1.01-1.02), and lack of remote symptomatic SE aetiology (OR 0.48; 95% CI 0.32-0.72) were independently associated with RSE, while severe consciousness impairment (OR 4.26; 95% CI 1.44-12.60) and younger age (OR 0.96; 95% CI 0.95-0.99) correlated with SRSE; however, most SRSE episodes were not predicted by these variables. Mortality was 15.5% overall, higher in RSE (24.5%) and SRSE (37.9%) than in non-refractory SE (9.8%) (P < 0.001). SIGNIFICANCE: Super-refractory status epilepticus appears clearly less prevalent in this cohort than previously reported, probably as it is not restricted to intensive care unit. SRSE emerges in younger patients with marked consciousness impairment, pointing to the underlying severe clinical background, but these variables do not predict most SRSE developments. There is currently a knowledge gap for prediction of SRSE occurrence that needs to be filled.

Statins are associated with decreased mortality risk after status epilepticus.

BACKGROUND AND PURPOSE: Statins display anti-inflammatory and anti-epileptogenic properties in animal models, and may reduce the epilepsy risk in elderly humans; however, a possible modulating role on outcome in patients with status epilepticus (SE) has not been assessed. METHODS: This cohort study was based on a prospective registry including all consecutive adults with incident SE treated in our center between April 2006 and September 2012. SE outcome was categorized at hospital discharge into 'return to baseline', 'new disability' and 'mortality'. The role of potential predictors, including statins treatment on admission, was evaluated using a multinomial logistic regression model. RESULTS: Amongst 427 patients identified, information on statins was available in 413 (97%). Mean age was 60.9 (±17.8) years; 201 (49%) were women; 211 (51%) had a potentially fatal SE etiology; and 191 (46%) experienced generalized-convulsive or non-convulsive SE in coma. Statins (simvastatin, atorvastatin or pravastatin) were prescribed prior to admission in 76 (18%) subjects, mostly elderly. Whilst 208 (50.4%) patients returned to baseline, 58 (14%) died. After adjustment for established SE outcome predictors (age, etiology, SE severity score), statins correlated significantly with lower mortality (relative risk ratio 0.38, P = 0.046). CONCLUSION: This study suggests for the first time that exposure to statins before an SE episode is related to its outcome, involving a possible anti-epileptogenic role. Other studies are needed to confirm this intriguing finding.

[Antiepileptics in women of childbearing age and during pregnancy: comparison of specialized information with the current state of knowledge in Germany and Switzerland]. / Antiepileptika bei Frauen im gebärfähigen Alter und in der Schwangerschaft : Vergleich der Fachinformationen in Deutschland und der Schweiz mit dem aktuellen Wissensstand.

BACKGROUND: Healthcare professionals regularly read the summary of product characteristics (SmPC) as one of the various sources of information on the risks of drug use in women of childbearing age and during pregnancy. The aim of this article is to present an overview of the teratogenic potential of various antiepileptic drugs and to compare these data with the information provided by the SmPCs. METHODS: A literature search on the teratogenic risks of 19 antiepileptic agents was conducted and the results were compared with the information on the use in women of childbearing age and during pregnancy provided by the SmPCs of 38 commercial products available in Switzerland and Germany. RESULTS: The teratogenic risk is discussed in all available SmPCs. Quantification of the risk for birth defects and the numbers of documented pregnancies are mostly missing. Reproductive safety information in SmPCs showed poor concordance with risk levels reported in the literature. Recommendations concerning the need to monitor plasma levels and possibly perform dose adjustments during pregnancy to prevent treatment failure were missing in five Swiss and two German SmPCs. DISCUSSION: The information regarding use in women of childbearing age and during pregnancy provided by the SmPCs is heterogeneous and poorly reflects the current state of knowledge. Regular updates of SmPCs are warranted in order for these documents to be of reliable use for health care professionals.

[Multimodal neuromonitoring for the critical care management of acute coma]. / Neuromonitorage après coma aigu aux soins intensifs.

Management of neurocritical care patients is focused on the prevention and treatment of secondary brain injury, i.e. the number of pathophysiological intracerebral (edema, ischemia, energy dysfunction, seizures) and systemic (hyperthermia, disorders of glucose homeostasis) events that occur following the initial insult (stroke, hemorrhage, head trauma, brain anoxia) that may aggravate patient outcome. The current therapeutic paradigm is based on multimodal neuromonitoring, including invasive (intracranial pressure, brain oxygen, cerebral microdialysis) and non-invasive (transcranial doppler, near-infrared spectroscopy, EEG) tools that allows targeted individualized management of acute coma in the early phase. The aim of this review is to describe the utility of multimodal neuromonitoring for the critical care management of acute coma.

The impact of a history of status epilepticus for epilepsy surgery outcome.

OBJECTIVE: Patients with focal drug resistant epilepsy are excellent candidates for epilepsy surgery. Status epilepticus (SE) and seizure clusters (SC), described in a subset of patients, have both been associated with extended epileptogenic cerebral networks within one or both hemispheres. In this retrospective study, we were interested to determine if a history of SE or SC is associated with a worse surgical outcome. METHODS: Data of 244 patients operated between 2000 to 2018 were reviewed, with a follow-up of at least 2 years. Patients with a previous history of SE or SC were compared to operated patients without these conditions (control group, CG). RESULTS: We identified 27 (11%) and 38 (15.5%) patients with history of SE or SC, respectively. No difference in post-operative outcome was found for SE and SC patients. Compared to the control group, patients with a history of SE were diagnosed and operated significantly at earlier age(p = 0.01), and after a shorter duration of the disease (p = 0.027), but with a similar age of onset. SIGNIFICANCE: A history of SE or SC was not associated with a worse post-operative prognosis. Earlier referral of SE patients for surgery suggests a heightened awareness regarding serious complications of recurrent SE by the referring neurologist or neuropediatrician. While the danger of SE is evident, policies to underline the impact for SC or very frequent seizures might be an efficient approach to accelerate patient referral also for this patient group.

[Anti-neuronal antibodies: a rapidly developing field]. / Anticorps antineuronaux: un domaine en plein développement.

Anti-neuronal antibodies are implicated in various neurological syndromes that are sometimes associated with tumors. Depending on the antigenic target (nuclear, cytoplasmic or extracellular cell-surface or synaptic) the clinical presentation is different. In neurological syndromes associated with antibodies specific for intracellular antigens, the T-cell mediated immunological response predominates as pathogenic effector and the response to treatment is typically poor. In contrast, in syndromes related to antibodies against extracellular targets, the role of the antibodies is pathogenic and the neurological syndrome often responds better to immunomodulatory treatment, associated or not with an anti-tumoral treatment. We review the spectrum of anti-neuronal antibodies and their corresponding clinical and therapeutic characteristics.

[2012: news in neurology]. / Neurologie.

In 2012, intramuscular midazolam appears as effective as intravenous lorezepam for the first line treatment of convulsive status epilepticus. Perampanel, a new anti-epileptic drug, will be soon available. Two oral treatments are now available for stroke prevention in atrial fibrillation setting. The methylphenidate and the Tai Chi could increase the walk capacity of patients suffering from Parkinson disease. A comprehensive cardiac work-up is essential for some congenital myopathy. A new drug against migraine seems free from vasoconstrictive effect. Antioxidants are harmful in Alzheimer disease. Some oral medication will be available for multiple sclerosis.

Oral topiramate as an add-on treatment for refractory status epilepticus.

OBJECTIVES: Oral anti-epileptic drugs (AED) represent possible add-on options in refractory status epilepticus (SE). We report our experience in using topiramate (TPM) to treat SE unresponsive to sequential trials of multiple agents. MATERIALS AND METHODS: Over 57 months, we identified 11 SE patients treated with TPM in our hospital, all of them suffered from SE refractory to at least two treatments, and six had generalized SE. Nine patients were managed in the ICU and required intubation. RESULTS: We found a definite electro-clinical response in 2/11 patients, already evident after 12-96 h after TPM introduction, and a possible response in 2/11 patients (concomitantly with other AEDs); 7/11 did not respond. Partial-complex SE appeared to better respond than generalized-convulsive SE. One patient developed a severe nephrolithiasis. CONCLUSIONS: As compared to previous small series describing only patients responding to TPM, this unselected observation underscores the difficulty of treating refractory SE, regardless of the agent.

Intravenous lacosamide for treatment of status epilepticus.

OBJECTIVES: Treatment of established status epilepticus (SE) requires immediate intravenous anticonvulsant therapy. Currently used first-line drugs may cause potentially hazardous side effects. We aimed to assess the efficacy and safety of intravenous lacosamide (LCM) in SE after failure of standard treatment. METHODS: We retrospectively analyzed 39 patients (21 women, 18 men, median age 62 years) from the hospital databases of five neurological departments in Germany, Austria and Switzerland between September 2008 and January 2010 who were admitted in SE and received at least one dose of intravenous LCM. RESULTS: Types of SE were generalized convulsive (n = 6), complex partial (n = 17) and simple partial (n = 16). LCM was administered after failure of benzodiazepins or other standard drugs in all but one case. Median bolus dose of LCM was 400 mg (range 200-400 mg), which was administered at 40-80 mg/min in those patients where infusion rate was documented. SE stopped after LCM in 17 patients, while 22 patients needed further anticonvulsant treatment. The success rate in patients receiving LCM as first or second drug was 3/5, as third drug 11/19, and as fourth or later drug 3/15. In five subjects, SE could not be terminated at all. No serious adverse events attributed to LCM were documented. CONCLUSIONS: Intravenous LCM may be an alternative treatment for established SE after failure of standard therapy, or when standard agents are considered unsuitable.

[Narcolepsy with cataplexy associated with H1N1 vaccination]. / Narcolepsie avec cataplexie après vaccination anti-H1N1.

INTRODUCTION: It has been suggested that the H1N1 vaccine may be a trigger for the onset of narcolepsy-cataplexy, a rare disease whose autoimmune origin is suspected. OBSERVATIONS: We report two patients (a 9-year-old boy and an 18-year-old man) with severe narcolepsy-cataplexy, in whom the illness appeared within 3-4 weeks after H1N1 vaccination. In both cases, symptoms developed unusually abruptly and they presented with severe daytime sleepiness and multiple daily cataplexy attacks. Other similar cases have been recently reported associated with H1N1 vaccine. CONCLUSION: Although no formal link can be established, the unusual characteristics of the reported cases and the striking temporal relationship suggests that narcolepsy may be the result of an autoimmune reaction triggered by H1N1 vaccination in susceptible individuals.

[Therapeutic advances in neurology]. / Neurologie.

This article summarizes the main therapeutic advances of 2010 in the field of neurology. It focuses on aspects that are likely to change the care of patients in clinical practice. Among these, we discuss the new oral treatments that have proved to be effective in multiple sclerosis, the results of two large studies comparing endarterectomy and stenting in carotid stenosis, novel therapeutic approaches for the treatment of non-motor symptoms in Parkinson's disease as well as the results of several pharmacological studies in the field of epilepsy.

[Current drug treatment for epilepsy]. / Traitement médicamenteux actuel de l'épiepsie.

If one patient is diagnosed with epilepsy, the first treatment line is represented by medications, which allow a seizure control in at least 2/3 of patients. Following the steady development of new compounds, there are currently more than 20 antiepileptic agents on the market, and several more will appear in the near future. This review, focusing on the indications and pitfalls of the most used drugs, with a particular attention to the new ones, aims at improving the orientation among this multitude of options. Since there is almost no difference regarding the efficacy on seizures, it is rather the profile of comorbidities and possible (positive and negative) side effects that will allow to select the best antiepileptic drug for each specific clinical situation, permitting a patient-tailored approach.

[Autoimmune epilepsy]. / Epilepsies d'origine auto-immune.

There is increasing recognition of an autoimmune origin of pharmacoresistant epileptic disorders. Besides the paraneoplastic limbic encephalopathies (LE), reports of syndromes of non-paraneoplastic LE are increasingly reported in the last 5-10 years. Three antibodies are now relatively well described: Voltage-gated potassium channels (VGKC), glutamic acid decarboxylase (GAD) and N-methyl-D-aspartate receptor-(NMDA) antibodies. We review clinical syndromes, associated imaging and laboratory findings. While most reports arise from adult populations, children and adolescents are also concerned as evidenced by increasing observations. Early recognition is mandatory, since early immunomodulatory treatment appears to be related to significantly better outcome.

Clinical and advanced neurophysiology in the prognostic and diagnostic evaluation of disorders of consciousness: review of an IFCN-endorsed expert group.

The analysis of spontaneous EEG activity and evoked potentialsis a cornerstone of the instrumental evaluation of patients with disorders of consciousness (DoC). Thepast few years have witnessed an unprecedented surge in EEG-related research applied to the prediction and detection of recovery of consciousness after severe brain injury,opening up the prospect that new concepts and tools may be available at the bedside. This paper provides a comprehensive, critical overview of bothconsolidated and investigational electrophysiological techniquesfor the prognostic and diagnostic assessment of DoC.We describe conventional clinical EEG approaches, then focus on evoked and event-related potentials, and finally we analyze the potential of novel research findings. In doing so, we (i) draw a distinction between acute, prolonged and chronic phases of DoC, (ii) attempt to relate both clinical and research findings to the underlying neuronal processes and (iii) discuss technical and conceptual caveats.The primary aim of this narrative review is to bridge the gap between standard and emerging electrophysiological measures for the detection and prediction of recovery of consciousness. The ultimate scope is to provide a reference and common ground for academic researchers active in the field of neurophysiology and clinicians engaged in intensive care unit and rehabilitation.

[Status epilepticus prognosis in adults]. / Pronostic de l'état de mal chez l'adulte.

Most investigations on prognosis of status epilepticus (SE) have focused on mortality, and suggest that outcome basically depends on the etiological and biological background. However, some recent studies also suggest that SE itself could be an independent predictor of death. Conversely, very little work has been published concerning the impact of SE on cognition. As compared with a first brief epileptic seizure, an incident SE episode seems to increase the risk of developing epilepsy.