The Commission on Classification and Terminology and the Commission on Epidemiology of the International League Against Epilepsy (ILAE) have charged a Task Force to revise concepts, definition, and classification of status epilepticus (SE). The proposed new definition of SE is as follows: Status epilepticus is a condition resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms, which lead to abnormally, prolonged seizures (after time point t1 ). It is a condition, which can have long-term consequences (after time point t2 ), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures. This definition is conceptual, with two operational dimensions: the first is the length of the seizure and the time point (t1 ) beyond which the seizure should be regarded as "continuous seizure activity." The second time point (t2 ) is the time of ongoing seizure activity after which there is a risk of long-term consequences. In the case of convulsive (tonic-clonic) SE, both time points (t1 at 5 min and t2 at 30 min) are based on animal experiments and clinical research. This evidence is incomplete, and there is furthermore considerable variation, so these time points should be considered as the best estimates currently available. Data are not yet available for other forms of SE, but as knowledge and understanding increase, time points can be defined for specific forms of SE based on scientific evidence and incorporated into the definition, without changing the underlying concepts. A new diagnostic classification system of SE is proposed, which will provide a framework for clinical diagnosis, investigation, and therapeutic approaches for each patient. There are four axes: (1) semiology; (2) etiology; (3) electroencephalography (EEG) correlates; and (4) age. Axis 1 (semiology) lists different forms of SE divided into those with prominent motor systems, those without prominent motor systems, and currently indeterminate conditions (such as acute confusional states with epileptiform EEG patterns). Axis 2 (etiology) is divided into subcategories of known and unknown causes. Axis 3 (EEG correlates) adopts the latest recommendations by consensus panels to use the following descriptors for the EEG: name of pattern, morphology, location, time-related features, modulation, and effect of intervention. Finally, axis 4 divides age groups into neonatal, infancy, childhood, adolescent and adulthood, and elderly.

Super-refractory status epilepticus is defined as status epilepticus that continues or recurs 24 h or more after the onset of anaesthetic therapy, including those cases where status epilepticus recurs on the reduction or withdrawal of anaesthesia. It is an uncommon but important clinical problem with high mortality and morbidity rates. This article reviews the treatment approaches. There are no controlled or randomized studies, and so therapy has to be based on clinical reports and opinion. The published world literature on the following treatments was critically evaluated: anaesthetic agents, anti-epileptic drugs, magnesium infusion, pyridoxine, steroids and immunotherapy, ketogenic diet, hypothermia, emergency resective neurosurgery and multiple subpial transection, transcranial magnetic stimulation, vagal nerve stimulation, deep brain stimulation, electroconvulsive therapy, drainage of the cerebrospinal fluid and other older drug therapies. The importance of treating the identifying cause is stressed. A protocol and flowchart for managing super-refractory status epilepticus is suggested. In view of the small number of published reports, there is an urgent need for the establishment of a database of outcomes of individual therapies.

Over an 18-month period, all incident cases of neurological disorders were ascertained prospectively in an unselected urban population based in 13 general practices in the London area by a General Practice Linkage Scheme with the National Hospital for Neurology and Neurosurgery. In three of these practices, the lifetime prevalence of neurological disorders was also assessed. A population of 100 230 patients registered with participating general practices was followed prospectively for the onset of neurological disorders. Multiple methods of case finding were used to maintain accuracy. The age- and sex-adjusted incidence rates of neurological disorders were calculated. The lifetime prevalence of neurological disorders was surveyed in 27 658 of the patients. The age- and sex-adjusted incidence rates were calculated for major neurological conditions. [These are expressed as rates per 100 000 persons per annum, with 95% confidence intervals (CI) in parentheses]. The commonest of these were first cerebrovascular events, 205 (CI: 183, 230); shingles, 140 (CI: 104, 184); diabetic polyneuropathy, 54 (CI: 33, 83); compressive neuropathies, 49 (CI: 39, 61); epilepsy, 46 (CI: 36, 60); Parkinson's disease, 19 (CI: 12, 27); peripheral neuropathies, 15 (CI: 9, 23); CNS infections, 12 (CI: 5, 13); post-herpetic neuralgia, 11 (CI: 6, 17); and major neurological injuries, 10 (CI: 4, 11). Lifetime prevalence rates are also reported (expressed as rate per 1000 persons with 95% CI). The most prevalent conditions were: completed stroke, 9 (CI: 8, 11); transient ischaemic attacks, 5 (CI: 4, 6); active epilepsy, 4 (CI: 4, 5); congenital neurological deficit, 3 (CI: 3, 4); Parkinson's disease, 2 (CI: 1, 3); multiple sclerosis, 2 (CI: 2, 3); diabetic polyneuropathy, 2 (CI: 1, 3); compressive mononeuropathies, 2 (CI: 2, 3); and sub-arachnoid haemorrhage, 1 (CI: 0.8, 2). Overall, the onset of 625 neurological disorders was observed per 100 000 population annually. Six percent of the population had at some time had a neurological disorder. This is the first study of the incidence and lifetime prevalence of neurological disorders in recent times; we found that these disorders give rise to significant morbidity in the community.

Summary:Purpose: To evaluate the efficacy and tolerability of levetiracetam (LEV, Keppra) as add-on therapy in patients with refractory partial seizures.Methods: In this European multicenter, double-blind, randomized, placebo-controlled trial, LEV (500 or 1,000 mg twice daily) was compared with placebo as add-on therapy in 324 patients with uncontrolled simple or complex partial seizures, or both, with or without secondary generalization. After enrollment, three parallel groups were assessed during a baseline period of 8 or 12 weeks, followed by a 4-week titration interval and a 12-week evaluation period.Results: LEV significantly decreased partial seizure frequency compared with placebo. A reduction in seizure frequency of 250% occurred in 22.8% of patients in the 1,000-mg group and 3 1.6% of patients in the 2,000-mg group, compared with 10.4% of patients in the placebo group. Administration of LEV did not affect plasma concentrations of concomitant antiepileptic drugs or alter vital signs or laboratory parameters. No significant difference in the incidence of adverse events was observed between treatment groups (70.8% for the 1,000-mg group and 75.5% for the 2,000-mg group), or between the LEV and placebo groups (73.2% for placebo group). The most commonly reported adverse effects in the LEV group were asthenia, headache, and somnolence.Conclusions: The antiepileptic efficacy and tolerability of LEV (1,000 mg/d and 2,000 mg/d, administered in two divided doses) as add-on therapy was established in patients with refractory partial seizures in this clinical study.

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[NCT00700310]) evaluated perampanel, an a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, as adjunctive therapy for refractory partial seizures. We report post hoc analyses of pooled study data by randomized dose. Methods: Patients with partial seizures despite receiving 1-3 antiepileptic drugs were randomized to once-daily placebo, perampanel 8 or 12 mg (studies 304, 305), or placebo, perampanel 2, 4, or 8 mg (study 306). Studies included a 6-week baseline period and double-blind treatment phase (6-week titration; 13-week maintenance). Primary end points were median change in partial seizure frequency (baseline vs. double-blind phase) and percentage of patients achieving ! 50% reduction in seizure frequency (baseline vs. maintenance). Here, these end points, together with secondary, exploratory, and safety end points, were assessed using pooled study data. Key Findings: The pooled intent-to-treat analysis set (randomized, treated patients with any seizure data) included 1,478 patients. Median changes in partial seizure frequency were greater with perampanel than placebo (perampanel 4 mg, À23.3%; 8 mg, À28.8%; 12 mg, À27.2%; placebo, À12.8%; p < 0.01, each dose vs. placebo), as were 50% responder rates (perampanel 4 mg, 28.5%; 8 mg, 35.3%; 12 mg, 35.0%; placebo, 19.3%; p < 0.05, each dose vs. placebo). In addition, median changes in complex partial plus secondary generalized seizure frequency were also greater with perampanel than placebo (perampanel 4 mg, À31.2%; 8 mg, À35.6%; 12 mg, À28.6%; placebo, À13.9%). Perampanel was generally well tolerated. The most frequent treatment-emergent adverse events (TEAEs) were dizziness, somnolence, and headache. Most TEAEs were mild/moderate; relatively few patients experienced severe TEAEs (placebo, 5.4%; perampanel, 8.9%) or serious TEAEs (placebo, 5.0%; perampanel, 5.5%). There were no deaths and no clinically important mean changes in laboratory values, electrocardiography (ECG) findings, or vital signs. Significance: Perampanel reduced partial seizure frequency and improved responder rates compared with placebo, with an acceptable tolerability profile.

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The objective of the current article was to review the literature and discuss the degree of evidence for various treatment strategies for status epilepticus (SE) in adults. We searched MEDLINE and EMBASE for relevant literature from 1966 to January 2005 and in the current updated version all pertinent publications from January 2005 to January 2009. Furthermore, the Cochrane Central Register of Controlled Trials (CENTRAL) was sought. Recommendations are based on this literature and on our judgement of the relevance of the references to the subject. Recommendations were reached by informative consensus approach. Where there was a lack of evidence but consensus was clear, we have stated our opinion as good practice points. The preferred treatment pathway for generalised convulsive status epilepticus (GCSE) is intravenous (i.v.) administration of 4-8 mg lorazepam or 10 mg diazepam directly followed by 18 mg/kg phenytoin. If seizures continue more than 10 min after first injection, another 4 mg lorazepam or 10 mg diazepam is recommended. Refractory GCSE is treated by anaesthetic doses of barbiturates, midazolam or propofol; the anaesthetics are titrated against an electroencephalogram burst suppression pattern for at least 24 h. The initial therapy of non-convulsive SE depends on type and cause. Complex partial SE is initially treated in the same manner as GCSE. However, if it turns out to be refractory, further non-anaesthetising i.v. substances such levetiracetam, phenobarbital or valproic acid should be given instead of anaesthetics. In subtle SE, in most patients, i.v. anaesthesia is required.