Relationship of white matter hyperintensities with clinical features of seizures in patients with epilepsy / A relação das hiperintensidades da substância branca com as características clínicas das crises em pacientes com epilepsia

ABSTRACT Background: Although epilepsy is primarily known as a cortical disorder, there is growing body of research demonstrating white matter alterations in patients with epilepsy. Objective: To investigate the prevalence of white matter hyperintensities (WMH) and its association with seizure characteristics in patients with epilepsy. Methods: The prevalence of WMH in 94 patients with epilepsy and 41 healthy controls were compared. Within the patient sample, the relationship between the presence of WMH and type of epilepsy, frequency of seizures, duration of disease and the number of antiepileptic medications were investigated. Results: The mean age and sex were not different between patients and healthy controls (p>0.2). WMH was present in 27.7% of patients and in 14.6% of healthy controls. Diagnosis of epilepsy was independently associated with the presence of WMH (ß=3.09, 95%CI 1.06-9.0, p=0.039). Patients with focal epilepsy had higher prevalence of WMH (35.5%) than patients with generalized epilepsy (14.7%). The presence of WMH was associated with older age but not with seizure characteristics. Conclusions: WMH is more common in patients with focal epilepsy than healthy controls. The presence of WMH is associated with older age, but not with seizure characteristics.

RESUMO Antecedentes: Embora a epilepsia seja principalmente conhecida como um distúrbio cortical, há um crescente corpo de pesquisas que demonstra alterações na substância branca em pacientes com epilepsia. Objetivo: Investigar a prevalência de hiperintensidades da substância branca (WMH) e sua associação com características das crises em pacientes com epilepsia. Métodos: A prevalência de WMH em 94 pacientes com epilepsia e 41 controles saudáveis ​​foi comparada. Na amostra de pacientes, foi investigada a relação entre a presença de WMH e o tipo de epilepsia, a frequência das crises, a duração da doença e o número de medicamentos antiepilépticos. Resultados: A média de idade e o sexo não diferiram entre pacientes e controles saudáveis ​​(p>0,2). WMH estava presente em 27,7% dos pacientes, enquanto em 14,6% dos controles saudáveis. O diagnóstico de epilepsia foi independentemente associado à presença de WMH (ß=3,09, IC95% 1,06-9,0, p=0,039). Pacientes com epilepsia focal apresentaram maior prevalência de WMH (35,5%) do que pacientes com epilepsia generalizada (14,7%). A presença de WMH foi associada à idade avançada, mas não a características das crises. Conclusões: Pacientes com epilepsia focal têm WMH mais comum do que controles saudáveis. A presença de WMH está associada à idade avançada, mas não a características das crises epilépticas.

[Diagnosis and treatment of status epilepticus in the intensive care unit]. / Diagnose und Behandlung des Status epilepticus auf der Intensivstation.

Both convulsive and nonconvulsive status epilepticus are associated with a high risk of morbidity and mortality. To limit brain damage, emergency investigation of etiology and treatment must be done synchronously. This review presents the general rules for treatment. The steps of pharmacologic escalation with benzodiazepines, antiepileptics, and anesthetics are discussed together with their advantages and disadvantages.

Perampanel: Does it have broad-spectrum potential?

This article reviews the profile of perampanel, a novel noncompetitive α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor antagonist, and its role as a potential broad-spectrum antiepileptic drug in the treatment of epilepsy. For this narrative review, data were collected using specified search criteria. Articles reporting the evidence for perampanel's efficacy from preclinical models, phase 3 clinical studies, observational studies, and descriptive evidence were included. AMPA receptors play a key role in mediating the action of glutamate at the excitatory synapse. Preclinical research showed the AMPA receptor blockade to constitute a promising target for antiepileptic drug therapy. In animal models, perampanel proved to be protective against seizures and reduce seizure severity and duration. Four phase-3 randomized controlled trials (3 in patients with focal seizures and one in primary generalized tonic-clonic seizures in idiopathic generalized epilepsy) have been completed. In focal (partial) onset seizures, perampanel (4, 8, and 12 mg) significantly reduced seizure frequency per 28 days (23.3%-28.8% vs 12.8%; P < .01) and responder rates (≥50% reduction in seizures) (28.5%-35.3% vs 19.3%; P < .05) compared with placebo. In primary generalized tonic-clonic seizures, perampanel 8 mg resulted in greater reduction in seizure frequency per 28 days (-76.5% vs -38.4%; P < .0001) and responder rate (64.2% vs 39.5%; P = .0019) than placebo. The efficacy, safety, and tolerability of perampanel have been reproduced in real-world clinical practice, and the agent has been shown to be effective in other epilepsy syndromes. Perampanel is a potentially broad-spectrum antiepileptic drug with a novel mechanism of action that may be a useful addition for patients with epilepsy with various seizure types. The availability of novel antiepileptic drugs for epilepsy treatment enables more individualized treatment for these patients.

Lacosamide for uncontrolled primary generalized tonic-clonic seizures: An open-label pilot study with 59-week extension.

OBJECTIVE: Assess the safety of adjunctive lacosamide for the treatment of uncontrolled primary generalized tonic-clonic seizures in patients (16-65 years) with primary generalized (genetic) epilepsy (PGE). METHODS: An open-label pilot safety study (SP0961; NCT01118949), comprising 12 weeks' historical baseline, 4 weeks' prospective baseline, 3 weeks' titration (target: 400mg/day adjunctive lacosamide) and 6 weeks' maintenance. Patients who continued to the extension study (SP0962; NCT01118962) then received ≤59 weeks of flexible treatment (100-800mg/day lacosamide with flexible dosing of concomitant antiepileptic drugs). The primary outcomes for SP0961 were the mean change (±standard deviation) in absence seizure or myoclonic seizure days per 28days from prospective baseline to maintenance; for SP0962, the incidence of treatment-emergent adverse events (TEAEs) and withdrawals because of TEAEs. RESULTS: Of the 49 patients who enrolled, 40 (82%) completed the pilot study and 9 discontinued (5 because of adverse events). Of the 39 patients who continued to the extension study, 10 discontinued (2 owing to TEAEs) and 29 (74%) completed the study. During the pilot study, patients reported a reduction in mean (±standard deviation) absence and myoclonic seizure days per 28days (-0.37±4.80, -2.19±5.80). Reductions were also observed during the extension study (-2.38±5.54, -2.78±6.43). Five patients in SP0961 and 2 patients in SP0962 experienced TEAEs of new or increased frequency of absence seizures or myoclonic seizures. The most common TEAEs during SP0961 were dizziness (39%) and nausea (27%), and during SP0962 were dizziness (26%) and upper respiratory tract infection (26%). CONCLUSIONS: The safety profile of adjunctive lacosamide was similar to that previously published. Adjunctive lacosamide did not systematically worsen absence or myoclonic seizures, and appears to be well tolerated in patients with PGE.

Voxel-based morphology study of idiopathic generalized epilepsy patients with typical absence seizure / 中华实用儿科临床杂志

Objective To observe the alterations in brain gray matter volume(GMV)in idiopathic generalized epilepsy(IGE)patients with typical absence seizure. Methods Nine IGE patients with typical absence seizure and 16 healthy volunteers were prospectively recruited from People's Hospital of Zhengzhou University from September 2012 to January 2014. By using a 3. 0T magnetic resonance imaging(MRI)and voxel - based morphometry(VBM)method, their whole brain structures and their brain GMV were scanned and analyzed,respectively,then the changes in GMV were observed. Results Compared with healthy control group,brain GMV extensively decreased in IGE patients with typical absence seizure. Thirteen regions with significant differences were as follows:the right rectal gyrus(t = 3. 13,P ﹤0. 01),the left rectal gyrus(t = 4. 82,P ﹤ 0. 01),the right calcarine/ cuneus/ gyrus lingualis/ occipital gyrus/ inferior oc-cipital gyrus(t = 6. 86,P ﹤ 0. 01),right gyrus lingualis(t = 4. 01,P ﹤ 0. 01),the left gyrus lingualis/ inferior occipital gyrus(t = 3. 73,P ﹤ 0. 01),the left inferior occipital gyrus/ gyrus lingualis(t = 5. 42,P ﹤ 0. 01),the left middle occipi-tal gyrus(t = 3. 76,P ﹤ 0. 01),the right middle occipital gyrus/ superior occipital gyrus/ middle temporal gyrus( t =3. 85,P ﹤ 0. 01),left middle temporal gyrus/ superior temporal gyrus(t = 5. 06,P ﹤ 0. 01),the right precuneus/ cuneus (t = 3. 33,P ﹤ 0. 01),and the right superior parietal lo-bule(t = 3. 66,P ﹤ 0. 01),right precentral gyrus(t = 3. 44,P ﹤0. 01),right superior frontal gyrus/ paracentral lobule/ supplementary motor area(t = 3. 50,P ﹤ 0. 01). However,GMV increase was not found. Conclusions Brain GMV extensively decreased in 13 brain regions of IGE patients with typical absence seizure,and among them occipital lobe is the most significant.

The clinical-electroencephalographic features of the 6 patients with idiopathic generalized epilepsy in adults with phantom absences / 中华神经科杂志

Objective To investigate the clinical and electroencephalogram (EEG) features of patients with idiopathic generalized epilepsy in adults with phantom absences.Methods Six patients were referred to the clinic of epilepsy from April,2007 to December,2011.They all had clinical assessment,EEG,or video EEG confirming absences seizure.Results Six patients showed the following similar clinical-EEG features:(1) mild ictal impairment of consciousness associated with generalized 3.0-3.5 Hz spike and slow wave discharges; (2) late-onset generalized tonic-clonic seizures; (3) absence status epilepticus with or without secondary generalized tonic-clonic seizures; (4) generalized discharges were mostly seen in three types in the awaking stage:fragmented discharge (＜4 s),brief discharge (4-10s) and long-time discharge (＞ 10 s).None of the patients had myoclonic jerks or photosensitivity.One patient' s mother had a history of generalized tonic clonic seizures.One patient had a history of children absence epilepsy and one patient had a history of febrile convulsion in the age of 1-3.Conclusion Idiopathic generalized epilepsy with phantom absences has distinct clinical and EEG features and may become a new idiopathic generalized epilepsy syndrome in adults.