Epidemiology of status epilepticus in adults: A population-based study on incidence, causes, and outcomes.

OBJECTIVE: In 2015, the International League Against Epilepsy (ILAE) proposed a new definition of status epilepticus (SE): 5 minutes of ongoing seizure activity to diagnose convulsive SE (CSE, ie, bilateral tonic-clonic SE) and 10 minutes for focal SE and absence SE, rather than the earlier criterion of 30 minutes. Based on semiology, several types of SE with prominent motor phenomena at any time (including CSE) were distinguished from those without (ie, nonconvulsive SE, NCSE). We present the first population-based incidence study applying the new 2015 ILAE definition and classification of SE and report the impact of the evolution of semiology and level of consciousness (LOC) on outcome. METHODS: We conducted a retrospective population-based incidence study of all adult patients with SE residing in the city of Salzburg between January 2011 and December 2015. Patients with hypoxic encephalopathy were excluded. SE was defined and classified according to the ILAE 2015. RESULTS: We identified 221 patients with a median age of 69 years (range 20-99 years). The age- and sex-adjusted incidence of a first episode of SE, NCSE, and SE with prominent motor phenomena (including CSE) was 36.1 (95% confidence interval [CI] 26.2-48.5), 12.1 (95% CI 6.8-20.0), and 24.0 (95% CI 16.0-34.5; including CSE 15.8 [95% CI 9.4-24.8]) per 100 000 adults per year, respectively. None of the patients whose SE ended with or consisted of only bilateral tonic-clonic activity died. In all other clinical presentations, case fatality was lower in awake patients (8.2%) compared with patients with impaired consciousness (33%). SIGNIFICANCE: This first population-based study using the ILAE 2015 definition and classification of SE found an increase of incidence of 10% compared to previous definitions. We also provide epidemiologic evidence that different patterns of status evolution and LOCs have strong prognostic implications.

Perampanel in patients with refractory and super-refractory status epilepticus in a neurological intensive care unit: A single-center audit of 30 patients.

In refractory status epilepticus (SE), γ-aminobutyric acidergic drugs become less effective and glutamate plays a major role in seizure perpetuation. Data on the efficacy of perampanel (PER) in treatment of refractory SE in humans are limited. Here, we present a single-center case series of patients with refractory SE who received PER orally in an intensive care unit. We retrospectively analyzed treatment response, outcome, and adverse effects of all patients with refractory SE in our Neurological Intensive Care Unit who received add-on PER between September 2012 and February 2018. Thirty patients with refractory SE (median = 72 years, range = 18-91, 77% women) were included. In 14 patients (47%), a high-dose approach was used, with a median initial dose of 24 mg (range = 16-32). In five patients (17%), SE could be terminated after PER administration (median dose = 6 mg, range = 6-20 mg, 2/5 patients in high-dose group). Clinical response was observed after a median of 24 hours (range = 8-48 hours), whereas electroencephalogram resolved after a median of 60 hours (range = 12-72 hours). Time to treatment response tended to be shorter in patients receiving high-dose PER (median clinical response = 16 hours vs 18 hours; electroencephalographic response = 24 hours vs 72 hours), but groups were too small for statistical analysis. Continuous cardiorespiratory monitoring showed no changes in cardiorespiratory function after "standard" and "high-dose" treatment. Elevated liver enzymes without clinical symptoms were observed after a median of 6 days in seven of 30 patients (23%; 57% high dose vs 43% standard dose), of whom six also received treatment with phenytoin (PHT). Outcome was unfavorable (death, persistent vegetative state) in 13 patients (43%; 39% high dose vs 61% standard dose), and good recovery (no significant disability, moderate disability) was achieved in nine patients (56% high dose vs 44% standard dose). Oral PER in loading doses up to 32 mg were well tolerated but could terminate SE only in a few patients (5/30; 17%). Long duration of SE, route of administration, and severe underlying brain dysfunction might be responsible for the modest result. An intravenous formulation is highly desired to explore the full clinical utility in the treatment of refractory SE.

Diagnostic and prognostic value of noninvasive long-term video-electroencephalographic monitoring in epilepsy surgery: A systematic review and meta-analysis from the E-PILEPSY consortium.

OBJECTIVE: The European Union-funded E-PILEPSY network (now continuing within the European Reference Network for rare and complex epilepsies [EpiCARE]) aims to harmonize and optimize presurgical diagnostic procedures by creating and implementing evidence-based guidelines across Europe. The present study evaluates the current evidence on the diagnostic accuracy of long-term video-electroencephalographic monitoring (LTM) in identifying the epileptogenic zone in epilepsy surgery candidates. METHODS: MEDLINE, Embase, CENTRAL, and ClinicalTrials.gov were searched for relevant articles. First, we used random-effects meta-analytical models to calculate pooled estimates of sensitivity and specificity with respect to postsurgical seizure freedom. In a second phase, we analyzed individual patient data in an exploratory fashion, assessing diagnostic accuracy within lesional and nonlesional temporal lobe epilepsy (TLE) and extratemporal lobe epilepsy (ETLE) patients. We also evaluated seizure freedom rate in the presence of "localizing" or "nonlocalizing" LTM within each group. The quality of evidence was assessed using the QUADAS-2 tool and the GRADE approach. RESULTS: Ninety-four studies were eligible. Forty-four were included in sensitivity meta-analysis and 34 in specificity meta-analysis. Pooled sensitivity was 0.70 (95% confidence interval [CI] = 0.60-0.80) and specificity was 0.40 (95% CI = 0.27-0.54). Subgroup analysis was based on individual data of 534 patients (41% men). In lesional TLE patients, sensitivity was 0.85 (95% CI = 0.81-0.89) and specificity was -0.19 (95% CI = 0.13-0.28). In lesional ETLE patients, a sensitivity of 0.47 (95% CI = 0.36-0.58) and specificity of 0.35 (95% CI = 0.21-0.53) were observed. In lesional TLE, if LTM was localizing and concordant with resection site, the seizure freedom rate was 247 of 333 (74%), whereas in lesional ETLE it was 34 of 56 (61%). The quality of evidence was assigned as "very low." SIGNIFICANCE: Long-term video-electroencephalographic monitoring is associated with moderate sensitivity and low specificity in identification of the epileptogenic zone. Sensitivity is remarkably higher in lesional TLE compared to lesional ETLE. Substantial heterogeneity across the studies indicates the need for improved design and quality of reporting.

Testing patients during seizures: A European consensus procedure developed by a joint taskforce of the ILAE - Commission on European Affairs and the European Epilepsy Monitoring Unit Association.

There is currently no international consensus procedure for performing comprehensive periictal testing of patients in the epilepsy monitoring units (EMUs). Our primary goal was to develop a standardized procedure for managing and testing patients during and after seizures in EMUs. The secondary goal was to assess whether it could be implemented in clinical practice (feasibility). A taskforce was appointed by the International League Against Epilepsy (ILAE)-Commission on European Affairs and the European Epilepsy Monitoring Unit Association, to develop a standardized ictal testing battery (ITB) based on expert opinion and experience with various local testing protocols. ITB contains a comprehensive set of 10 items that evidence the clinically relevant semiologic features, and it is adaptive to the dynamics of the individual seizures. The feasibility of the ITB was prospectively evaluated on 250 seizures from 152 consecutive patients in 10 centers. ITB was successfully implemented in clinical practice in all 10 participating centers and was considered feasible in 93% of the tested seizures. ITB was not feasible for testing seizures of very short duration.

A randomized, double-blind comparison of antiepileptic drug treatment in the elderly with new-onset focal epilepsy.

OBJECTIVE: To compare the effectiveness of controlled-released carbamazepine (CR-CBZ) to levetiracetam (LEV) and to lamotrigine (LTG) in elderly patients with newly diagnosed focal epilepsy. METHODS: Randomized, double-blind, parallel-group trial conducted between January 2007 and August 2011, in 47 ambulatory or hospital sites in Germany, Austria, or Switzerland. Eligible participants were aged ≥ 60, had new-onset epilepsy, had no acute illness as the cause of their seizures, and had no contraindication to the drugs in the trial. Patients were randomized 1:1:1 to CR-CBZ, LTG, or LEV. Doses were up-titrated for 6 weeks and could be maintained or adjusted depending on seizure relapse or tolerability over an additional period of 52 weeks. Primary outcome was the retention to treatment at week 58; secondary measures related to seizure and adverse event frequency. RESULTS: Of 361 randomized patients, 359 were included (CR-CBZ n = 121, LTG n = 117, LEV n = 122) in the modified intent-to-treat population (mean age [range] 71.4 [60-95] years). At week 58, the retention rate for LEV was significantly higher than for CR-CBZ (61.5% vs. 45.8%, p = 0.02), and similar to LTG (55.6%). Seizure freedom rates at weeks 30 and 58 were not different across the groups. Twice as many patients receiving CR-CBZ discontinued due to adverse events or death compared to those in the LEV group (32.2% vs. 17.2%; odds ratio 2.28, 95% confidence interval [CI] 1.25-4.19, p = 0.007), whereas discontinuation was intermediate for LTG (26.3%). Median daily doses of completers (n = 195) were CR-CBZ 380.0 mg/day (333.0-384.0), LTG 95 mg/day (94.0-97.0), and LEV 950 mg/day (940.0-985.0). SIGNIFICANCE: In the initial monotherapy of focal epilepsy in the elderly, 1-year retention to LEV was higher compared to CR-CBZ due to better tolerability. Retention of LTG was intermediate and close to LEV, but did not differ significantly from either comparators. NCT00438451, www.clinicaltrials.gov.

Duration of focal complex, secondarily generalized tonic-clonic, and primarily generalized tonic-clonic seizures--A video-EEG analysis.

INTRODUCTION: Identifying seizures with prolonged duration during video-electroencephalographic (EEG) monitoring is of importance to inform clinicians when to start emergency treatment of seizures to prevent status epilepticus. The aims of this study were to assess the clinical and EEG seizure duration (SD) in consecutive patients with epilepsy who underwent prolonged video-EEG monitoring and to identify a seizure type-dependent time point to start emergency treatment based on the likelihood that seizures will not stop spontaneously. Furthermore, we sought to determine predictors of SD and explored the relationship between antiepileptic drug (AED) serum levels and SD. MATERIAL AND METHODS: We retrospectively analyzed 1796 seizures in 200 patients undergoing video-EEG monitoring between January 2006 and March 2008. RESULTS: Focal simple seizures lasted significantly shorter (clinical SD: 28s, EEG SD: 42 s) compared with focal complex seizures (clinical SD: 64 s, EEG SD: 62 s), and both seizure types lasted significantly shorter compared with secondarily generalized tonic-clonic seizures (GTCSs; clinical SD: 90 s, EEG SD: 96 s). There was no difference between the duration of the convulsive phase of primary GTCSs (defined as nonfocal) and that of secondarily GTCSs (each 65 s). Cumulative clinical SD (99%) was 7 min in focal complex seizures and 11 min in focal simple seizures. Mixed linear regression model demonstrated that history of status epilepticus (P = 0.034), temporal lobe seizure onset (P = 0.040), and MRI lesions (P = 0.013) were significantly associated with logarithmic EEG SD in focal epilepsies recorded with scalp electrodes. We found significant negative correlations between the AED serum level and the EEG SD in patients treated with monotherapy: carbamazepine (P < 0.001), levetiracetam (P = 0.001), oxcarbazepine (P = 0.001), and valproic acid (P = 0.038) but not with lamotrigine monotherapy and EEG SD. DISCUSSION: Based on the results of this study, we propose 2 min of convulsive seizure activity (irrespective of focal or generalized onset) as a prolonged seizure, which could serve as a time point to consider treatment to prevent status epilepticus. In focal complex seizures, we suggest an upper limit of 7 min, and in focal simple seizures 11 min, as definition of prolonged seizures. History of status epilepticus, temporal seizure onset, and lesional MRI findings are factors associated with significantly longer SD. Negative correlations of carbamazepine, levetiracetam, oxcarbazepine, and valproic acid serum levels and SD suggest a prolonging effect on seizures during withdrawal of these AEDs during video-EEG monitoring sessions. This article is part of a Special Issue entitled "Status Epilepticus".

The demise of Archbishop Wolf Dietrich--A historical note on a fatal status epilepticus documented at Salzburg in 1617.

INTRODUCTION: Wolf Dietrich of Raitenau (WD) ruled the archiepiscopal Salzburg from March 2nd 1587 to December 17th 1611. He was condemned by his successor Archbishop Markus Sittikus of Hohenems to spend his last years imprisoned at the Fortress Hohensalzburg, where he died on January 16th 1617. This historical note describes the causes of his death. MATERIALS AND METHODS: The original Latin handwriting, including the detailed medical history and the autopsy of the Archbishop's body performed by his personal physician, was analyzed in conjunction with historical handwritings provided by St. Peter's Abbey, Salzburg handwriting assigned to Markus Sittikus. RESULTS: Wolf Dietrich of Raitenau had his first well-documented left hemispheric stroke in winter 1604/05. He had palsy of his right arm, was unable to write, and, therefore, used a stamp instead of his signature until October 1605. After another stroke, right hemispheric in origin with persisting palsy of his left arm ["leva corporis pars iam pridem simili ex apoplectico assultu in paralysin resoluta"], he developed symptomatic epilepsy with recurring seizures ["epileptico insultu quo etiam alias correptus est"]. On January 15th 1617, he suffered from a secondarily generalized convulsive status epilepticus ["toto corpore convellitur epileptico insultu"] with stertorous breathing and distortion of his face ["spuma stertore insigni faciei perversione"] and was unconscious for 8h. He recovered from coma and showed dysphagia, buccofacial apraxia ["abolitam diglutiendi facultatem"], reversible speech disturbance ["accisa etiam verba loqui"], and left-sided hemiplegia ["leva corporis pars… immobilis prorsus est reddita"]. The following day, he had speech disturbances, and he died at noon. His autopsy showed large but intact liver ["hepar magnum sanum"] and heart ["cor magnum in quo lapsus nullus"]. There was intrapulmonal mucus ["pituita imbutus"], and part of the lungs adhered to its pleura. He had five kidney stones and a partly cirrhotic spleen. The cause of his death was assumed to be intracerebral ["causa mortis in capite requienda fuisset"]. DISCUSSION: The terminal suffering of Wolf Dietrich of Raitenau is the first witnessed case report on a fatal status epilepticus in Salzburg. Most likely, he suffered from vascular epilepsy due to a right hemispheric stroke, leading to status epilepticus with left-sided Todd's palsy and speech disturbances. An acute symptomatic etiology of this disease cannot be ruled out, as for religious reasons, the Archbishop's brain was not autopsied. CONCLUSION: Meticulous medical reporting including autopsy was already available in Salzburg in 1617, and the symptomatic etiology of epilepsy was diagnosed correctly. This article is part of a Special Issue entitled "Status Epilepticus".

Standardized computer-based organized reporting of EEG: SCORE.

The electroencephalography (EEG) signal has a high complexity, and the process of extracting clinically relevant features is achieved by visual analysis of the recordings. The interobserver agreement in EEG interpretation is only moderate. This is partly due to the method of reporting the findings in free-text format. The purpose of our endeavor was to create a computer-based system for EEG assessment and reporting, where the physicians would construct the reports by choosing from predefined elements for each relevant EEG feature, as well as the clinical phenomena (for video-EEG recordings). A working group of EEG experts took part in consensus workshops in Dianalund, Denmark, in 2010 and 2011. The faculty was approved by the Commission on European Affairs of the International League Against Epilepsy (ILAE). The working group produced a consensus proposal that went through a pan-European review process, organized by the European Chapter of the International Federation of Clinical Neurophysiology. The Standardised Computer-based Organised Reporting of EEG (SCORE) software was constructed based on the terms and features of the consensus statement and it was tested in the clinical practice. The main elements of SCORE are the following: personal data of the patient, referral data, recording conditions, modulators, background activity, drowsiness and sleep, interictal findings, "episodes" (clinical or subclinical events), physiologic patterns, patterns of uncertain significance, artifacts, polygraphic channels, and diagnostic significance. The following specific aspects of the neonatal EEGs are scored: alertness, temporal organization, and spatial organization. For each EEG finding, relevant features are scored using predefined terms. Definitions are provided for all EEG terms and features. SCORE can potentially improve the quality of EEG assessment and reporting; it will help incorporate the results of computer-assisted analysis into the report, it will make possible the build-up of a multinational database, and it will help in training young neurophysiologists.

On the recovery of disorders of consciousness under intrathecal baclofen administration for severe spasticity-An observational study.

BACKGROUND: Occasionally, patients show dramatic recovery from disorders of consciousness (DOC) under intrathecal baclofen (ITB), an established treatment option for severe supraspinal spasticity. Anecdotal explanations for ITB-related recovery of cognition include modulation of afferent impulses at the spinal level, thereby reducing spasticity-related proprioceptive information overload within cortico-thalamo-cortical connections. OBJECTIVE: In this retrospective patient chart analysis, we assessed whether a reduction in spasticity would be associated with an increase in Coma Recovery Scale revised (CRS-R) scores in a larger sample of patients than previously published. METHODS: From a hospital-based ITB treatment register, we extracted data from 26 patients with DOC and severe supraspinal spasticity who improved by >2 points on the Coma Recovery Scale revised (CRS-R) within 6 months after ITB treatment initiation. We assessed Modified Ashworth scale (MAS) scores and CRS-R scores on admission (PRE) and 3 and 6 months after initiation of ITB treatment (3M, 6M). We performed correlation analysis of the scores and their respective changes (PRE to 3M, 3M to 6M). We also correlated the time from acute event until ITB initiation to CRS-R scores at 3M and 6M. RESULTS: ITB led to significant improvement in spasticity based on MAS scores, which did not correlate to the improvements seen in CRS-R total and subscale scores. Daily ITB dose did neither correlate to MAS scores nor to CRS-total scores in the whole patient group, but after 3 months, ITB dose correlated to some CRS-R subscale scores in some patient subgroups. Time until ITB treatment did not correlate to CRS-R scores later on. CONCLUSIONS: Our data confirm that ITB may exert beneficial effects in selected DOC patients with respect to improved cognitive functions, which, however, do not correlate to its antispastic effect. The lack of correlation between time to ITB and CRS-R outcome, but significant CRS-R improvements following pump implantation, renders spontaneous remissions unlikely and leaves room for alternative pharmacological mechanisms.

Intravenous lacosamide in status epilepticus and seizure clusters.

Status epilepticus (SE) and seizure clusters (SC) represent neurologic emergencies with a case fatality rate up to 34%, depending on cause and comorbidity. As SE becomes more refractory to treatment over time, appropriate medication is important. This study aimed to investigate efficacy and tolerability of intravenous (IV) lacosamide (LCM) in treatment of SC and SE. Data of patients with SE or SC who were treated with IV LCM between December 2009 and February 2011 in two Austrian centers were analyzed retrospectively. Clinical information was extracted from patients' charts. Forty-eight patients (26f/22m) aged median 62 years (range 17-95 years) were identified. Thirty-five percent of patients (17 of 48) had SC and 65% (31 of 48) had SE. SE was nonconvulsive in 10 (32%), convulsive in 11 (36%), and focal in 10 (32%) patients. SE was acute symptomatic in six (20%) and remote symptomatic in 11 (35%) patients. Fourteen (45%) had preexisting epilepsy. Median initial bolus dose was 200 mg (range 200-400 mg) in patients with SE and 200 mg in patients with SC. Maximum infusion rate was 60 mg/min. Cessation was observed in 42 patients (88%). Success rate in patients with SE receiving LCM as first or second drug was 100% (8 of 8), as third drug 81% (11 of 15), and as fourth or later drug 75% (6 of 8). There were no side effects observed except for pruritus and skin rash in two patients. These data support use of IV LCM as a potential alternative to standard antiepileptic drugs for acute treatment of seizure emergency situations, although randomized controlled studies are needed.

Video-EEG monitoring: safety and adverse events in 507 consecutive patients.

PURPOSE: Video-electroencephalography (EEG) monitoring plays a central role in the presurgical evaluation of medically refractory epilepsies and the diagnosis of nonepileptic attack disorders (NEADs). The aim of this study was to analyze safety and adverse events (AEs) during video-EEG monitoring. METHODS: We retrospectively evaluated 596 video-EEG sessions in 507 patients (233 men, mean age 36 years, standard deviation = 14, range 9-80 years) within a 6-year period. AEs were examined in detail and their risk factors were assessed using multiple logistic regression analysis. KEY FINDINGS: Forty-four patients (9%) experienced 53 AEs: 20 had psychiatric events (17 postictal psychosis, 2 panic attacks, 1 interictal psychosis), 15 had injuries (14 falls with minor injuries, 2 falls with fractures, 2 fractures without fall, 1 fall with epidural hematoma), 10 patients had 13 episodes of status epilepticus (SE), and one AE was treatment-related (valproic acid--induced encephalopathy). Patients with AEs were older (p = 0.036) and had a longer duration of epilepsy (p = 0.019). All AEs resulted in a prolonged hospital stay (p < 0.001). Ninety-one percent of the AEs occurred within the first 4 days of monitoring. Independent risk factors were duration of epilepsy >17 years [odds ratio (OR) 3.096; 95% confidence interval (CI) 1.548-6.189], a previous history of psychiatric illness (OR 16.882; 95% CI 5.469-52.110), a history of seizure-related injuries (OR 3.542; 95% CI 1.069-11.739), or a history of SE (OR 3.334; 95% CI 1.297-8.565). SIGNIFICANCE: The most common AEs were postictal psychosis, falls, and SE. Patients with an older age, long disease duration, psychiatric comorbidity, history of injuries, and SE have a higher risk.

Complications After Dual Placement of a Baclofen Pump and Ventricular Shunt in Individuals With Severe Brain Injury.

OBJECTIVE: To assess the complications of dual placement of an intrathecal baclofen (ITB) pump and a ventriculoperitoneal shunt (VPS) in people with severe brain injury. DESIGN: Case series. SETTING: Referral center, ambulatory, and hospitalized care. PARTICIPANTS: Referred sample (N=9) composed of 5 men and 4 women with severe brain injuries (5 traumatic brain injuries, 3 subarachnoid hemorrhages, 1 intracerebral hemorrhage) and a mean disease duration of 6±4.5 years (range, 0.5-11.4y). INTERVENTION: Both systems (ie, an ITB device and a VPS system) were implanted in all participants. MAIN OUTCOME MEASURES: We assessed the number and type of complications that occurred after implantation of the second system, as well as subsequent interventions. RESULTS: The ITB delivery system was implanted after the VPS system in 5 patients (ITB group), and the VPS system was the second implanted system in 4 groups (VPS group). Seven complications occurred in 7 patients after implantation of the second system, 4 in the ITB group and 3 in the VPS group. Three of the complications were drug-related, 2 were procedure-related, and 2 were device-related. The complication occurred within 4 days after implantation of the second system in 6 patients. CONCLUSIONS: Complications are frequent in patients who undergo implantation of both an ITB delivery device and a VPS system. Drug-related complications were more common. Complications occurred more often when an ITB device was implanted as the second system. The critical period is the first 4 days.

Asymmetric seizure termination in primary and secondary generalized tonic-clonic seizures.

PURPOSE: In temporal lobe epilepsies an asymmetric termination (AST) of the clonic phase of secondary generalized tonic-clonic seizures (sGTCS) reliably lateralizes the side of seizure onset. The last clonic activity occurs ipsilateral to the side of the seizure onset zone. We compared the prevalence and lateralizing value of AST in sGTCS of frontal and temporal lobe origin as well as in primary generalized tonic-clonic seizures (pGTCS). METHODS: We analyzed 177 seizures in 84 consecutive patients. Forty-one patients had temporal lobe epilepsy (TLE), 24 frontal lobe epilepsy (FLE), and 19 had nonfocal (primary) generalized epilepsies (GE). All patients underwent intensive video-EEG (electroencephalography) monitoring, high-resolution magnetic resonance imaging (MRI), neuropsychological testing, and single photon emission computed tomography/positron emission tomography (SPECT/PET) when feasible. Two investigators blinded for diagnosis, EEG, and imaging data assessed frequency and side of the last clonic jerk. RESULTS: AST occurred in 63% of patients with TLE (47% of seizures), in 71% with FLE (60% of seizures), and in 42% with GE (21% of seizures). These results were not significant for patients, but significant for seizures in TLE versus GE and in FLE versus GE (p < 0.001). The positive predictive value (PPV) for the side of seizure onset was 74% (p = 0.003) in TLE and 75% (p = 0.008) in FLE. DISCUSSION: AST in sGTCS lateralizes the side of seizure onset in TLE and in FLE to the ipsilateral hemisphere with a high PPV. However, AST was also observed in GE. Therefore, asymmetric clinical signs should not inevitably lead to the assumption of focal epilepsy syndromes.

Successful surgery in late onset epilepsy with tuberous sclerosis complex.

[Case records of Epileptic Disorders. Anatomo-electro clinical correlations. Case 01-2009]. Tuberous sclerosis complex (TSC) is a multisystem genetic disorder with variable phenotypic expression, caused by mutations in one of the two tumor suppressor genes, TSC1 or TSC2. Epilepsy is the most common neurological presentation and seizures are often medically intractable. Definition of the epileptogenic zone during presurgical evaluation is challenging given the multiple potentially epileptogenic lesions visible on MRI. However, TSC patients may nevertheless achieve seizure freedom, when preoperative evaluation yields concordant results. The strategies used in these patients vary substantially among different epilepsy surgery centres. We present a 21-year-old right-handed, intellectually not impaired woman with TSC and medically intractable seizures since the age of 15 years. Careful multi-stage presurgical evaluation, including prolonged video-EEG-monitoring, cerebral high resolution MRI, ictal and interictal [99m Tc]HMPAO-SPECT, [18 F]FDG-PET and further invasive recordings with subdural and depth electrodes led to the identification of an epileptogenic tuber with concordant seizure onset zone in the right neocortical temporal lobe. A tailored resection was performed leading to excellent surgical outcome (follow-up 12 months, Engel class I).

Intrathecal Baclofen in Hereditary Spastic Paraparesis.

Introduction: Treatment with intrathecal baclofen (ITB) is a therapeutic option in the management of severe spasticity in patients with hereditary spastic paraparesis (HSP). However, information on the impact of ITB on the natural course of disease, especially the effect of ITB on functional parameters over time is limited. Materials and Methods: We evaluated seven patients with HSP retrospectively who were treated with an ITB device. The following parameters were measured before (pre-implantation) and after implantation (post-implantation) of the ITB device at steady state dosage of ITB and annually until last follow-up: modified Ashworth Scale, Reflex Scale, modified Rankin Scale, and Rivermead Mobility Index. The ITB dosages were assessed after reaching steady state as well as annually until last follow-up. Results: The ITB device was implanted 13 ± 6 (range 9-16) years after diagnosis of HSP on average. Severe spasticity was controlled in all patients by a mean baclofen dosage of 188 ± 60 (range 145-230) µg per day at steady state post-implantation. The modified Ashworth Scale improved significantly from 3 (interquartile range [IQR] 3-3.25) to 1 (IQR 1-1.25; p = 0.046), as did the Reflex Scale from 5 (IQR 4.75-5) to 3 (IQR 2.75-3; p = 0.046) at steady state dosage of ITB. The modified Rankin Scale improved from 2 (IQR 2-2) to 1 (IQR 1-1.5; p = 0.083) and the Rivermead Mobility Index remained 14 (IQR 13.5-14 pre-implantation, IQR 14-14 post-implantation; p = 0.18). Post-implantation, spasticity improved for 2-3 years, followed by a stable phase of ambulatory and other mobility functions for 4-5 years. Thereafter, the maintenance or progressive loss of mobility depended on individual courses of the disease. No ITB-related severe side effects occurred. Discussion: Our data further support the role of ITB in the treatment of severe spasticity in patients with deteriorated walking performance suffering HSP. ITB therapy may initially improve spasticity and stabilize mobility functions for the first 6-8 years in patients with HSP.

A further case of familial ring chromosome 20 mosaicism - molecular characterization of the ring and review of the literature.

Ring chromosome 20 syndrome is a rare chromosomal disorder characterized by childhood-onset drug-resistant epilepsy, behavioral problems and variable cognitive impairment. While most cases occur sporadically, parent-to-child transmission of ring 20 mosaicism has only been reported in a few exceptional families. We identified a further family with mother-to-child transmission of ring 20 mosaicism. Detailed characterization of the ring chromosome showed a complete ring with preserved telomere repetitive sequences. SNP genotyping excluded mosaic uniparental disomy and indicated that the chromosome was transmitted without recombination from mother to child. These results corroborate the findings of a previous study and support the hypothesis that inherited mosaicism is due to transmission of an unstable chromosome either prone to ring opening or to ring re-formation.

Absence status in the elderly as a late complication of idiopathic generalized epilepsies.

The main categories of nonconvulsive status epilepticus are: complex partial and absence status. Absence status was reported to occur de novo in later life as a situation-related, single event. We report four cases of absence status with presentation after the age of 60 years. At admission, no history of epilepsy had been mentioned. The preliminary diagnosis of absence status occurring de novo in later life had to be changed on completion of case histories. All patients had suffered from idiopathic generalized epilepsy with absence seizures, which had resolved after puberty. A second peak of IGE, with repeated episodes of absence status after the menopause and without identifiable triggering factors is assumed.

Personalized safety measures reduce the adverse event rate of long-term video EEG.

Objective: Safety in epilepsy monitoring units (EMUs) has become an increasing concern because adverse events occur in up to 10% of patients undergoing long-term video EEG in EMUs. The aim of this study was to assess the effectiveness of a specific safety protocol in an EMU. Methods: We retrospectively assessed the adverse event rates in a group without (group 1, 84-month period, Innsbruck, Austria) and a group with (group 2, 33-month period, Salzburg, Austria) personalized safety measures utilizing a standardized protocol for long-term epilepsy monitoring in high-risk patients. Differences in adverse event rates during and after long-term video EEG between the two groups were calculated and compared. Results: In group 1, 44/507 (9%, 95% confidence interval [CI] 6.5-11.5%) patients experienced 53 adverse events: 20/507 (4%, 95% CI 2.6-6.0%) patients had psychiatric events, 15/507 (3%, 95% CI 1.8-4.8%) patients sustained a total of 19 injuries during seizures, and 10/507 (2%, 95% CI 1.1-3.6%) patients had 13 episodes of status epilepticus; one adverse event was treatment-related (valproic acid-induced encephalopathy; 1/507, 0.2%, 95% CI 0.0-1.1%). By using the new safety protocol in group 2, the adverse event rate was only 5% (95% CI 3.4-7.6%; 30 adverse events in 26/491; 45% reduction; p = 0.036), in contrast. These events included 13 psychiatric complications in 13/491 (2%, 95% CI 1.6-4.5%, p = 0.252) patients, 12 seizure-related injuries in 9/491 (2%, 95% CI 1.0-3.4%, p = 0.250) patients, and 5 episodes of status epilepticus in 4/491 (1%, 95% CI 0.3-2.1%, p = 0.120) patients. Significance: Implementation of personalized safety measures in high-risk patients resulted in a clinically relevant reduction of adverse events in the EMU. Safety protocols are a valid tool to reduce the occurrence of adverse events in EMUs.

(S)-Ketamine in Refractory and Super-Refractory Status Epilepticus: A Retrospective Study.

OBJECTIVE: The aim was to describe the safety and efficacy of (S)-ketamine [(S)-KET] in a series of patients with refractory and super-refractory status epilepticus (RSE and SRSE) in a specialized neurological intensive care unit (NICU). METHODS: We retrospectively analyzed the data of patients with RSE and SRSE treated with (S)-KET in the NICU, Salzburg, Austria, from 2011 to 2015. Data collection included demographic features, clinical presentation, diagnosis, electroencephalogram (EEG) data, anticonvulsant treatment, timing, and duration of treatment with (S)-KET. Outcomes were seizure control and death. RESULTS: A total of 42 patients (14 women) with RSE and SRSE were treated with (S)-KET. The median duration of status epilepticus (SE) was 10 days [first quartile (Q1) 5.0, Q3 21.0]; the median latency from SE onset to the first administration of (S)-KET was 3 days (Q1 2.0, Q3 6.8). Prior to (S)-KET administration, patients had received a median of two (Q1 2.0, Q3 3.0) anesthetics and three (Q1 2.0, Q3 4.0) antiepileptic drugs. Forty percent of patients (17/42) received propofol: 65 % prior to (S)-KET; 35 % at the same time with (S)-KET. Seven patients received a median bolus of (S)-KET of 200 mg (Q1 200, Q3 250) followed by a continuous infusion, while 35 started with a continuous infusion (maximum rate median 2.55 mg/kg/h; Q1 2.09, Q3 3.22). In 64 % of patients (27/42), (S)-KET was the last drug before SE cessation; in five patients, it was given with propofol at the same time. Median duration of administration was 4 days (Q1 2.0, Q3 6.8). Overall (S)-KET treatment was well tolerated, adverse effects were not observed, and overall mortality was 45.2 %. CONCLUSIONS: Treatment of SRSE in adult patients with (S)-KET led to resolution of status in 64 %. No adverse events were found, indicating a favorable safety profile.

Perampanel for the treatment of primary generalized tonic-clonic seizures in idiopathic generalized epilepsy.

INTRODUCTION: The non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) - receptor antagonist perampanel (PER) was approved in 2015 for treatment of primary generalized tonic-clonic seizures (pGTCS). The aim of this narrative review is to summarize available data on pharmacological properties, efficacy and tolerability of PER in pGTCs. AREAS COVERED: Data sources included MEDLINE, EMBASE, Google Scholar and ClinicalTrials.gov, conference proceedings of the ILAE congresses and the most recent conference proceedings of the American Epilepsy Society (2013 to 2015). EXPERT OPINION: A placebo-controlled clinical phase III study including 164 patients (≥ 12 years) with pGTCS in idiopathic generalized epilepsies (IGE) demonstrated efficacy of PER in reducing pGTCS with good tolerability profile, and without aggravating absence seizures or myoclonic seizures. Dizziness, the main adverse event (AE), can be avoided by bedtime administration. Psychiatric AEs ranging from mild depression to aggression and suicidal attempts should be especially monitored in patients with a history of psychiatric disorders. Co-administration of enzyme inducing antiepileptic drugs (AEDs) might decrease PER plasma levels and make dose adjustment necessary. A reduced efficacy of progesterone-containing oral contraceptives should be considered when administering PER to young women. There is lack of evidence on PER treatment in pregnancy. Although no teratogenic effects were observed in animal models, PER is not recommended for women of childbearing age without contraception.