Bilateral synchronous gamma range firing of bulbar motor units during tonic seizures.

We present a patient with tonic seizures of the bulbar muscles. Video-EEG recording during the multiple attacks showed no ictal EEG abnormalities. The tonic seizures were clearly visible as EMG artefacts on the EEG recording and consisted of 3-6 symmetric tonic bursts of EMG activity of 2-4 seconds and an interval of 2-6 seconds. Spectral analysis showed a very distinct, bilateral synchronous, dominant gamma peak on the EMG spectra during the seizures with a cross correlation of 0.67 between left and right without a time lag. We discuss whether this peak originates from the firing frequencies of the bulbar motor units, and whether this is consistent with the Piper rhythm described during maximal voluntary contraction in controls and related to firing in the gamma range of the cortical motor neurons. We conclude that the EMG artefacts recorded on EEG during seizures can be informative with regards to the type and pathophysiology of epilepsy.

Exploratory polysomnographic evaluation of pregabalin on sleep disturbance in patients with epilepsy.

OBJECTIVES: To evaluate the effects of adjunctive pregabalin 300 mg/day versus placebo on polysomnographic (PSG) variables in patients with well controlled partial seizures and subjectively reported sleep disturbance. METHODS: An exploratory, 4-week, double-blind, randomized study in patients with well controlled partial seizures on AED monotherapy and subjective sleep disturbance over the previous 6 months. Mean changes from baseline to endpoint in PSG and subjective sleep variables (MOS Sleep Scale, Groningen Sleep Questionnaire) in patients on adjunctive pregabalin 300 mg/day (n=8) were compared with patients on placebo (n=7). RESULTS: Baseline PSGs showed sleep fragmentation. Mean sleep efficiency improved significantly in both treatment groups in the mean baseline to endpoint change; there was no significant between-group difference. Pregabalin treatment was associated with a significant reduction in number of awakenings (p = 0.02), and improvement in wake time after sleep onset approached significance (p = 0.055), suggesting improvement in sleep continuity that was not observed in the placebo group. Pregabalin was also associated with significant improvements in the MOS sleep disturbance and sleep quantity subscales compared with placebo (p < or =0.03). There were no changes in self-reported seizure control. CONCLUSIONS: This exploratory pilot study suggests that pregabalin may improve sleep continuity in patients with clinically relevant sleep disturbance. The effect on disturbed sleep appears independent of seizure control. The effects of pregabalin on disturbed sleep and seizures and their interrelationships warrant further study.

A novel splicing mutation in KCNQ2 in a multigenerational family with BFNC followed for 25 years.

PURPOSE: A large multigenerational family with benign familial neonatal convulsions (BFNC) was revisited to identify the disease-causing mutation and to assess long-term outcome. METHODS: We supplemented the original data with recent clinical and neurophysiologic data on patients and first-degree relatives, including information on seizure recurrence. We conducted linkage analysis at the EBN1 and EBN2 loci, followed by mutation analysis of KCNQ2. We evaluated the qualitative effect of the KCNQ2 mutation at the messenger RNA (mRNA) level by using reverse-transcribed total RNA isolated from leukocytes. RESULTS: Thirteen relatives had a history of neonatal convulsions, 11 of whom showed remission within 2 months. One patient showed an atypical course of neonatal convulsions, developing photosensitive myoclonic epilepsy at age 13 years. We found suggestive linkage of the BFNC phenotype to the 20q13-EBN1 locus (lod score, 2.03) and an intronic mutation IVS14-6 C>A in KCNQ2 segregating with the trait in all affected members, but absent in 100 unrelated control subjects. This mutation creates a new, preferentially used, splice site. Alternative splicing adds 4 nt containing a premature stop codon to the transcript, resulting in a truncated protein after position R588. CONCLUSIONS: We detected and characterized a novel splicing mutation in the brain-specific KCNQ2 gene by using easily accessible blood leukocytes. Aberrant splicing cosegregates with BFNC but not with photosensitivity.

Subjective sleep disturbance in patients with partial epilepsy: a questionnaire-based study on prevalence and impact on quality of life.

PURPOSE: This study was designed to assess whether sleep disturbance is more frequent among patients with partial seizures and what impact on quality of life (QoL) sleep disturbance may have on patients with partial seizures. METHODS: Questionnaire booklets were mailed to 1,183 patients from four Dutch clinics. Each patient was asked to find two age- and gender-matched controls to complete the same set of questionnaires [Sleep Diagnosis List (SDL), Medical Outcomes Study (MOS)-Sleep Scale, Groningen Sleep Questionnaire, Epworth Sleepiness Scale, and the SF-36 Health Survey]. The prevalence of sleep disturbance, based on the SDL, was compared between those with partial epilepsy and controls. Mean scores on sleep and the SF-36 Physical (PCS) and Mental (MCS) Component Summary scales were compared. RESULTS: Responses from 486 patients and 492 controls were analyzed. Respondents with partial epilepsy had a highly significant, twofold higher prevalence of sleep disturbance compared with controls (38.6 vs. 18.0%; p < 0.0001). Most sleep-disorder subscales showed significant abnormalities in respondents with epilepsy, compared with controls. Mean SF-36 MCS and PCS scores were significantly lower in respondents with epilepsy compared with controls in both the strata with sleep disturbance and without (all p values <0.05). The presence of a sleep disturbance in respondents with epilepsy was associated with the greatest impairment in QoL. CONCLUSIONS: Sleep disturbance is more than twice as prevalent in persons with partial epilepsy compared with controls, and most domains of sleep are significantly disturbed. Persons with partial epilepsy have significant QoL impairment, and sleep disturbance further compounds this.