Stroke‐related epilepsy

Stroke is the cause of about 10% of all epilepsy and 55% of newly diagnosed seizures among the elderly. Although recent advances in acute stroke therapy have improved longevity, there has been a consequent rise in the prevalence of stroke‐related epilepsy (STRE). Many clinical studies make a distinction between early (within 7 days of onset of stroke) and late (beyond 7 days of onset of stroke) seizures based on presumed pathophysiological differences. Although early seizures are thought to be the consequence of local metabolic disturbances without altered neuronal networks, late seizures are thought to occur when the brain has acquired a predisposition for seizures. Overall, STRE has a good prognosis, being well controlled by antiepileptic drugs. However, up to 25% of cases become drug resistant. STRE can also result in increased morbidity, longer hospitalization, greater disability at discharge and greater resource utilization. Additional controlled trials are needed to explore the primary and secondary prevention of STRE as well as to provide high‐quality evidence on efficacy and tolerability of antiepileptic drugs to guide treatment of STRE. Robust pre‐clinical and clinical prediction models of STRE are also needed to develop treatments to prevent the transformation of infarcted tissue into an epileptic focus.     

Concept of epilepsy surgery and presurgical evaluation

Epilepsy surgery is a well‐accepted treatment for drug‐resistant epilepsy. The success of the epilepsy surgery depends upon an appropriate presurgical evaluation process which should ensure the selection of suitable patients who are likely to become seizure‐free following surgery without any unacceptable deficit. The two basic goals of the presurgical evaluation are the accurate localization and delineation of the extent of the epileptogenic zone, and its complete and safe resection. The process of the presurgical evaluation requires a multimodality approach wherein each modality provides unique and complimentary information which is combined with the information provided by other modalities to generate a hypothesis with regard to the likely epileptogenic zone. The basic modalities for the presurgical evaluation are clinical history, long‐term video‐EEG recording, high‐resolution MRI, and neuropsychological evaluation. The additional modalities include functional imaging studies, electrical and magnetic source imaging, functional MRI, and intracranial monitoring. Each modality has its own limitations and the information provided by none of them is absolute. Hence, a concordance among the different modalities is the key to surgical success. The presurgical evaluation is a step‐wise process starting form the most basic and most reliable tests and progressing to more complex and invasive modalities. The number of tests required varies according to the complexity involved and may include very basic minimum investigations in a given case, to the use of all the available investigations in more complex cases. The proper selection of various investigations and their accurate interpretation at each stage is required to ensure a successful outcome. In this article, we intend to review some of these basic concepts of presurgical evaluation and epilepsy surgery, and try to provide a frame work of the presurgical evaluation process.     

Outcome of vagus nerve stimulation for drug‐resistant epilepsy: the first three years of a prospective Japanese registry

Aims. Vagus nerve stimulation (VNS) is an established option of adjunctive treatment for patients with drug‐resistant epilepsy, however, evidence for long‐term efficacy is still limited. Studies on clinical outcomes of VNS in Asia are also limited. We report the overall outcome of a national, prospective registry that included all patients implanted in Japan. Methods. The registry included patients of all ages with all seizure types who underwent VNS implantation for drug‐resistant epilepsy in the first three years after approval of VNS in 2010. The registry excluded patients who were expected to benefit from resective surgery. Efficacy analysis was assessed based on the change in frequency of all seizure types and the rate of responders. Changes in cognitive, behavioural and social status, quality of life (QOL), antiepileptic drug (AED) use, and overall AED burden were analysed as other efficacy indices. Results. A total of 385 patients were initially registered. Efficacy analyses included data from 362 patients. Age range at the time of VNS implantation was 12 months to 72 years; 21.5% of patients were under 12 years of age and 49.7% had prior epilepsy surgery. Follow‐up rate was >90%, even at 36 months. Seizure control improved over time with median seizure reduction of 25.0%, 40.9%, 53.3%, 60.0%, and 66.2%, and responder rates of 38.9%, 46.8%, 55.8%, 57.7%, and 58.8% at three, six, 12, 24, and 36 months of VNS therapy, respectively. There were no substantial changes in other indices throughout the three years of the study, except for self/family‐accessed QOL which improved over time. No new safety issues were identified. Conclusions. Although this was not a controlled comparative study, this prospective national registry of Japanese patients with drug‐resistant epilepsy, with >90% follow‐up rate, indicates long‐term efficacy of VNS therapy which increased over time, over a period of up to three years. The limits of such trials, in terms of AED modifications and during follow‐up and difficulties in seizure counting are also discussed.     

The impact of epilepsy on sleep architecture during childhood

Purpose: The effect of etiology on the relationship between epilepsy and sleep during childhood has not been studied in detail. The aim of this study was to evaluate differences in sleep structure in drug-resistant epilepsies with different underlying causes. Methods: We studied 31 patients with drug-resistant epilepsies with or without a structural lesion (lesional and nonlesional) and compared their sleep architecture with that of normal controls and with that of a group of children with benign epilepsy with rolandic spikes (BERS). Subjects underwent a single-night polysomnographic recording. Sleep recordings were scored according to the American Academy of Sleep Medicine (AASM) and cyclic alternating pattern (CAP) criteria. Key Findings: Compared to normal controls, patients with drug-resistant epilepsy showed a significant reduction of time in bed, total sleep time, rapid eye movement (REM) sleep, sleep stage N3, and sleep efficiency, and a significant increase in wake after sleep onset. The lesional subgroup showed a reduction in total sleep time and sleep latency and an increase in REM latency and wake after sleep onset. No significant differences, however, were found comparing the lesional and nonlesional subgroups. When compared to BERS, patients with drug-resistant epilepsy showed a significant reduction in sleep stage N3, REM sleep, and sleep efficiency. Regarding CAP analysis, when compared to controls, the drug-resistant group had an increased A1% and a decreased A2%, with a decrease of A1 index in N3 and a global decrease of A2 and A3 indexes. The lesional subgroup showed a slight increase of A1% with a decrease of A1 index in N3 and a global decrease of A2 and A3 indexes. Drug-resistant epilepsy, compared to benign epilepsy showed an increase of CAP rate in N2 and of A1 index in N1 and N2 but not in N3; A2 and A3 indexes were similar in both, but patients with drug-resistant epilepsy showed a significant reduction of A3 index in N1. Significance: Our findings suggest that the presence of structural cerebral abnormalities may play an important role in disrupting sleep architecture.     

Research progress of vagus nerve stimulation in the treatment of epilepsy

The International League Against Epilepsy (ILAE) defined drug‐resistant epilepsy (DRE) that epilepsy seizure symptoms cannot be controlled with two well‐tolerated and appropriately chosen antiepileptic drugs, whether they are given as monotherapy or in combination. According to the WHO reports, there is about 30%‐40% of epilepsy patients belong to DRE. These patients need some treatments other than drugs, such as epilepsy surgery, and neuromodulation treatment. Traditional surgical approaches may be limited by the patient's clinical status, pathological tissue location, or overall prognosis. Thus, neuromodulation is an alternative choice to control their symptoms. Vagus nerve stimulation (VNS) is one of the neuromodulation methods clinically, which have been approved by the Food and Drug Administration (FDA). In this review, we systematically describe the clinical application, clinical effects, possible antiepileptic mechanisms, and future research directions of VNS for epilepsy.     

Expression pattern of Mical-1 in the temporal neocortex of patients with intractable temporal epilepsy and pilocarpine-induced rat model

Mical-1 is a novel F-actin-disassembly factor that is critical in actin reorganization. It provides a molecular conduit through which actin reorganizes-a hallmark of cell morphological changes, including axon navigation. However, whether Mical-1 is involved in the epileptogenesis remains unknown. Here, we investigate Mical-1 expression pattern in patients with intractable temporal lobe epilepsy (TLE) and pilocarpine-induced rat model. We used double-labeled immunoflurescence, immunohistochemistry, and Western blotting to assess the location and expression of Mical-1 in temporal neocortex of patients with intractable TLE, and the expression pattern of Mical-1 at different time point in the hippocampus and temporal lobe cortex of the pilocarpine-induced rat model. Double-labeled immunofluorescence showed that Mical-1 was coexpressed with neuron-specific enolase (NSE) in the cytoplasm of neurons in temporal neocortex of patients with TLE and hippocampus of rat model. Faint and scattered immunoreactivity for Mical-1 in the neuron of temporal neocortex in TLE group, but strong immunoreactivity for Mical-1 was shown in control subjects. To quantitatively evaluate the Mical-1 immunoreactivity, we measured the mean optical density (OD) of Mical-1. In the hippocampus of pilocarpine-induced rat model, the OD values transient increased at 6 h after seizure then decreased from 1 day to 14 days, and returned to a subnormal level at 60 days. The lowest level of Mical-1 expression occurred at 14 days after seizure in the hippocampus. In the temporal lobe cortex of rat model, the OD values decreased at all time point after kindling compared to the normal group. Furthermore, our Western blot analysis confirmed these expression patterns of Mical-1 from latent stage to chronic stage. Our results indicate that in patients with TLE and pilocarpine-induced rat model, the expression of Mical-1 were followed a downtrend from the latent stage to chronic stage after seizure evoke. Thus, as an effect factor participated in F-actin disassemble, Mical-1 may associate with inner pathophysiological modulation in epilepsy.     

C-reactive protein and seizures in focal epilepsy: a video-electroencephalographic study

Purpose: C‐reactive protein (CRP) has been studied extensively in many noninflammatory neurologic conditions, but there has been little study of CRP in the context of seizures or epilepsy. The purpose of this study was to examine CRP concentrations in patients with refractory focal epilepsy who were undergoing video‐electroencephalography (EEG) monitoring compared with healthy controls, and CRP change during 24 h after a seizure. Methods: CRP levels were measured in serum at the onset of video‐EEG recording (CRP‐0h) and at 3, 6, 12, and 24 h after index seizure (the first verified localized‐onset seizure) in 31 patients during inpatient video‐EEG monitoring by using high sensitivity measurement of CRP concentration. The patients were categorized into two groups: temporal lobe epilepsy (TLE; n = 15) and extratemporal lobe epilepsy (XLE; n = 16). Eighty healthy volunteers served as controls. Key Findings: CRP‐0h concentration was significantly higher in patients with refractory focal epilepsy than in controls (3.5 vs. 0.7 mg/ml, p < 0.001). All five patients with elevated CRP‐0h (>mean + 2 standard deviations in controls) had TLE (vs. none in XLE; p = 0.018). Index seizure type was associated with CRP increase from baseline to maximum level after index seizure (p = 0.005). The most important predictor of increase in CRP level was secondarily generalized tonic–clonic seizure (SGTCS; p = 0.030). Significance: The higher baseline levels in patients with epilepsy compared with healthy controls demonstrates that CRP concentrations are also affected in refractory epilepsy. Our data suggest that SGTCS stimulates CRP production. These results emphasize the association between inflammation and refractory epilepsy.     

Long‐term employment of adults with childhood‐onset epilepsy: A prospective population‐based study

Purpose: Our aim was to determine the long‐term employment and predictive factors in adults with childhood‐onset epilepsy living in the community. Methods: A population‐based incidence cohort of 144 children prospectively followed since their first unprovoked seizure before the age of 16 years up to a mean age of 48. Results: At a mean age of 23 years (range 18–35 years) 85 (71%) of 119 patients living in the community were employed. Predictive of employment at a mean age of 23 were normal intelligence [odds ratio (OR) 14.5, 95% confidence interval (CI) 4.5–46.8, p < 0.01], vocational education (OR 15.2, 95% CI 2.9–79.9, p < 0.01), and age at onset of epilepsy older than 6 years (OR 4.9, 95% CI 1.3–19.2, p = 0.02). At the mean age of 48 years (range 43–59 years), 45 (59%) of 76 patients living in the community were employed, as were 63 (78%) of 81 controls (patients vs. controls, p = 0.01). In 40 (53%) of 76 surviving patients employed between age 23 and 48, four factors were found to predict employment: normal intelligence (OR 15.8; 95% CI 2.4–102.4, p < 0.01), having offspring (OR 6.1; 1.5–25.0, p = 0.01), uninterrupted 5‐year terminal remission (5YTR) from age 23 to age 48 (OR 4.8; 1.1–19.9, p = 0.03), and no history of status epilepticus (OR 12.8; 1.8–90.9, p = 0.01). Conclusions: Normal intelligence, onset of epilepsy at age older than 6, and good vocational education appear to predict employment in early adulthood. Normal intelligence, having offspring, uninterrupted remission, and no history of status epilepticus appear to predict lasting employment into middle age.     

Review: Molecular characteristics of long‐term epilepsy‐associated tumours (LEATs) and mechanisms for tumour‐related epilepsy (TRE)

Brain tumours are the second most common cause of seizures identified in epilepsy surgical series. While any tumour involving the brain has the potential to cause seizures, specific subtypes are more frequently associated with epilepsy. Tumour‐related epilepsy (TRE) has a profound impact on patients with brain tumours and these seizures are often refractory to anti‐epileptic treatments, resulting in long‐term disability and patient morbidity. Despite the drastic impact of epilepsy‐associated tumours on patients, they have not traditionally enjoyed as much attention as more malignant neoplasms. However, recently a number of developments have been achieved towards further understanding of the molecular and developmental backgrounds of specific epilepsy‐associated tumours. In addition, the past decade has seen an expansion in the literature on the pathophysiology of TRE. In this review, we aim to summarize the mechanisms by which tumours may cause seizures and detail recent data regarding the pathogenesis of specific developmental epilepsy‐associated tumours.     

Intraoperative ElectroCorticoGraphy (ECog): indications,techniques, and utility in epilepsy surgery

Aims. To describe the technique, indications, and utility of intraoperative ECoG monitoring during various surgeries for medically intractable epilepsy. Methods. Literature was reviewed to obtain published results on using intraoperative ECoG techniques for the surgical treatment of medically intractable epilepsy of various underlying aetiologies. Results. General intraoperative ECoG techniques were described, including effects of anaesthetic agents on intraoperative ECoG signals. Use of intraoperative ECoG in temporal lobe epilepsy with mesial temporal sclerosis (MTS) is generally considered not necessary, whereas intraoperative ECoG in temporal lobe epilepsy without mesial temporal sclerosis may provide useful information. Intraoperative ECoG in extra‐temporal epilepsy with structural lesions may facilitate resection, whereas the use of intraoperative ECoG in extra‐temporal epilepsy without a structural lesion is more controversial. Conclusions. Intraoperative ECoG is a useful technique to be employed in surgical treatment of medically intractable epilepsy. However, its effectiveness may vary depending on the underlying pathological causes of the seizures.