Cortical excitability correlates with seizure control and epilepsy duration in chronic epilepsy

OBJECTIVE: Cortical excitability differs between treatment responders and nonresponders in new‐onset epilepsy. Moreover, during the first 3 years of epilepsy, cortical excitability becomes more abnormal in nonresponders but normalizes in responders. Here, we study chronic active epilepsy, to examine whether cortical excitability continues to evolve over time, in association with epilepsy duration and treatment response. METHODS: We studied 28 normal subjects, 28 patients with moderately controlled epilepsy (≤4 seizures per year) and 40 patients with poorly controlled epilepsy (≥20 or more seizures per year). Resting motor threshold (RMT), active motor threshold (AMT), short‐interval intracortical inhibition (SICI), intracortical facilitation (ICF) and cortical silent period (CSP) were measured, using transcranial magnetic stimulation (TMS). Disease and treatment covariates were collected (age at onset of epilepsy, epilepsy duration, number of drugs prescribed, total drug load, sodium channel drug load). RESULTS: RMT and AMT were higher in patients than in normal subjects; RMT and AMT were higher in poorly controlled than moderately controlled patients. ICF at 12 msec and 15 msec were lower in poorly controlled patients than in normal subjects. Long‐interval intracortical inhibition (LICI) at 50 msec was higher in poorly controlled compared to moderately controlled patients. These differences were not explained by antiepileptic drug (AED) treatment or duration of epilepsy. RMT and AMT increased with duration in the poorly controlled group, but did not increase with duration in the moderately controlled group. INTERPRETATION: Cortical excitability differs markedly between moderately controlled and poorly controlled patients with chronic epilepsy, not explained by disease or treatment variables. Moreover, the evolution of cortical excitability over time differs, becoming more abnormal in the poorly controlled group

Revealing a brain network endophenotype in families with idiopathic generalised epilepsy

Idiopathic generalised epilepsy (IGE) has a genetic basis. The mechanism of seizure expression is not fully known, but is assumed to involve large-scale brain networks. We hypothesised that abnormal brain network properties would be detected using EEG in patients with IGE, and would be manifest as a familial endophenotype in their unaffected first-degree relatives. We studied 117 participants: 35 patients with IGE, 42 unaffected first-degree relatives, and 40 normal controls, using scalp EEG. Graph theory was used to describe brain network topology in five frequency bands for each subject. Frequency bands were chosen based on a published Spectral Factor Analysis study which demonstrated these bands to be optimally robust and independent. Groups were compared, using Bonferroni correction to account for nonindependent measures and multiple groups. Degree distribution variance was greater in patients and relatives than controls in the 6-9 Hz band (p = 0.0005, p = 0.0009 respectively). Mean degree was greater in patients than healthy controls in the 6-9 Hz band (p = 0.0064). Clustering coefficient was higher in patients and relatives than controls in the 6-9 Hz band (p = 0.0025, p = 0.0013). Characteristic path length did not differ between groups. No differences were found between patients and unaffected relatives. These findings suggest brain network topology differs between patients with IGE and normal controls, and that some of these network measures show similar deviations in patients and in unaffected relatives who do not have epilepsy. This suggests brain network topology may be an inherited endophenotype of IGE, present in unaffected relatives who do not have epilepsy, as well as in affected patients. We propose that abnormal brain network topology may be an endophenotype of IGE, though not in itself sufficient to cause epilepsy

Cingulate gyrus epilepsy

The cingulate gyrus is located above the corpus callosum and forms part of the limbic system. Cingulate gyrus epilepsy poses a diagnostic challenge, given its diverse and variable seizure semiology. We present two patients with seizures arising in the cingulate gyrus that highlight the electroclinical and imaging features of this rare form of epilepsy. Cingulate seizures can give a wide range of clinical manifestations, which relate to the underlying neuroanatomy and subdivisions of the cingulate cortex. Here, we review the semiology of cingulate epilepsy and how this relates to the location of seizure onset and patterns of propagation

Motor evoked potential polyphasia:A novel endophenotype of idiopathic generalized epilepsy

OBJECTIVE: We compared the motor evoked potential (MEP) phases using transcranial magnetic stimulation in patients with idiopathic generalized epilepsy (IGE), their relatives, and healthy controls, hypothesizing that patients and their unaffected relatives may share a subtle pathophysiologic abnormality. METHODS: In a cross-sectional study, we investigated 23 patients with IGE, 34 first-degree relatives, and 30 matched healthy controls. Transcranial magnetic stimulation was performed to produce a series of suprathreshold single-pulse MEPs. A semiautomated method was used to count phases. We compared between groups the mean number of MEP phases, the stimulus-to-stimulus variability in MEP phases, and the proportion of polyphasic MEPs within subjects. RESULTS: Patients with IGE and their relatives had a significantly increased number of MEP phases (median for patients 2.24, relatives 2.17, controls 2.01) and a significantly higher proportion of MEPs with more than 2 phases than controls (median for patients 0.118, relatives 0.088, controls 0.013). Patients had a greater stimulus-to-stimulus variability in number of MEP phases than controls. There were no differences between patients and relatives. CONCLUSION: Increased MEP polyphasia in patients with IGE and their first-degree relatives may reflect transient abnormal evoked oscillations. The presence of polyphasic MEPs in relatives as well as patients suggests that MEP polyphasia is not related to treatment, and is in isolation insufficient to predispose to epilepsy. Polyphasic MEP may be a novel endophenotype in IGE

Long-term outcomes after epilepsy surgery, a retrospective cohort study linking patient-reported outcomes and routine healthcare data

Objective: The objective of the study was to assess the long-term outcomes of epilepsy surgery between 1995 and 2015 in South Wales, UK, linking case note review, postal questionnaire, and routinely collected healthcare data.Method: We identified patients from a departmental database and collected outcome data from patient case notes, a postal questionnaire, and the QOLIE-31-P and linked with Welsh routinely collected data in the Secure Anonymised Information Linkage (SAIL) databank.Results: Fifty-seven patients were included. Median age at surgery was 34 years (11-70), median: 24 years (2-56) after onset of habitual seizures. Median follow-up was 7 years (2-19). Twenty-eight (49%) patients were free from disabling seizures (Engel Class 1), 9 (16%) experienced rare disabling seizures (Class 2), 13 (23%) had worthwhile improvements (Class 3), and 7 (12%) had no improvement (Class 4). There was a 30% mean reduction in total antiepileptic drug (AED) load at five years postsurgery. Thirty-eight (66.7%) patients experienced tonic-clonic seizures presurgery verses 8 (14%) at last review. Seizure-free patients self-reported a greater overall quality of life (QOL; QOLIE-31-P) when compared with those not achieving seizure freedom. Seizure-free individuals scored a mean of 67.6/100 (100 is best), whereas those with continuing seizures scored 46.0/100 (p < 0.006). There was a significant decrease in the median rate of hospital admissions for any cause after epilepsy surgery (9.8 days per 1000 patient days before surgery compared with 3.9 after p < 0.005).Significance: Epilepsy surgery was associated with significant improvements in seizures, a reduced AED load, and an improved QOL that closely correlated with seizure outcomes and reduced hospital admission rates following surgery. Despite this, there was a long delay from onset of habitual seizures to surgery. The importance of long-term follow-up is emphasized in terms of evolving medical needs and health and social care outcomes