Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0014547 (focal epilepsy)
 1,627 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanisms of the anticonvulsant activity of cannabidiol (CBD) and the central excitation of delta 9-tetrahydrocannabinol (delta 9-THC) were investigated electrophysiologically with conscious, unrestrained cobalt epileptic rats. The well-known antiepileptics, trimethadione (TMO), ethosuximide (ESM), and phenytoin (PHT), were included as reference drugs. Direct measurements were made of spontaneously firing, epileptic potentials from a primary focus on the parietal cortex and convulsions were monitored visually. ESM and TMO decreased the frequency of focal potentials, but PHT and CBD exerted no such effect. Although CBD did not suppress the focal abnormality, it did abolish jaw and limb clonus; in contrast, delta 9-THC markedly increased the frequency of focal potentials, evoked generalized bursts of polyspikes, and produced frank convlusions. 11-OH-delta 9-THC, the major metabolite of delta 9-THC, displayed only one of the excitatory properties of the parent compound: production of bursts of polyspikes. In contrast to delta 9-THC and its 11-OH metabolite, CBD, even in very high doses, did not induce any excitatory effects or convulsions. The present study provides the first evidence that CBD exerts anticonvulsant activity against the motor manifestations of a focal epilepsy, and that the mechanism of the effect may involve a depression of seizure generation or spread in the CNS.
 ...
PMID:The influence of cannabidiol and delta 9-tetrahydrocannabinol on cobalt epilepsy in rats. 11 6

Focal clonic seizures are a frequent epileptic phenomenon. However, there are little data about their pathomechanism. In four patients with focal epilepsy and subdural electrodes, focal clonus was elicited by electrical stimulation of the motor cortex. Three additional patients underwent intraoperative stimulation of the spinal cord. Rhythmic clonic muscle responses were elicited by cortical stimulation with 20-50 Hz. The clonus consisted of simultaneous trains of compound muscle action potentials (CMAP) in agonistic and antagonistic muscles alternating with periods of muscular silence despite continuous stimulation. Clonus frequency decreased from 4.0-8.0 Hz at 50 Hz stimulation to 3.0-3.5 Hz at 20 Hz paralleled by a prolongation of the trains of CMAP. The stimulation frequency correlated with the number of stimuli blocked during relaxation. During the stable stimulation periods, the clonus frequency decreased over time. The number of stimuli which formed a train of CMAP and which were blocked during relaxation increased towards the end of the stimulation periods. Increasing intensity of stimulation at the same frequency converted a clonic to a tonic response. There was always an 1:1 relationship between stimulus and CMAP during spinal cord stimulation. We hypothesize that during cortical stimulation, clonus is elicited by synchronous activation of pyramidal tract (PT) neurons which results in excitation of intracortical GABA(B)ergic interneurons by recurrent axon-collaterals. This leads to stepwise hyperpolarization of PT neurons intermittently suppressing the output of PT neurons despite continuous stimulation. This mechanism can explain our finding that temporal and spatial summation of the stimuli were needed for clonus generation.
 ...
PMID:Focal clonus elicited by electrical stimulation of the motor cortex in humans. 1235 Mar 91

Focal clonic seizures are a frequent epileptic phenomenon. However, there are few data about their pathogenesis. Eleven patients with focal epilepsy who experienced focal clonic seizures during prolonged video-EEG monitoring were included in this study. Nine patients had subdural electrodes on the precentral gyrus and one patient had additional bilateral subthalamic nucleus (STN) depth electrodes. In five patients, the EEG was co-registered with the EMG of muscles which were involved in the clonic seizures. The frequency, pattern and evolution of the ictal EEG were analysed and their relationship to STN and EMG activity was studied. Focal clonic seizures were always associated with a polyspike-wave pattern in the EEG of the primary motor area (frequency range 1.6-3.4 Hz), while neighbouring electrodes not overlying the precentral gyrus showed different EEG patterns. At seizure onset, the ictal EEG derived from the precentral gyrus consisted of repetitive spiking for 8-28 s (median 19.5 s), accompanied by a continuous increase in muscle tone. This evolved to a pattern of polyspike-wave complexes which were associated with clinical clonus and lasted for 14-202 s (median 30.5 s). The clonic muscle contractions consisted of bursts of compound muscle action potentials (CMAPs) which occurred synchronously in agonistic and antagonistic muscles and were separated by periods of complete muscle relaxation. Each series of CMAPs followed the polyspikes in the EEG with a latency of 17-50 ms. The periods of muscle relaxation occurred during the EEG slow waves. Only some of the cortical spikes were followed by ipsilateral STN spikes. CMAPs followed the cortical polyspikes independently of whether or not STN spikes were seen. The study suggests that focal clonic seizures are focal tonic-clonic seizures. The epileptic clonus consisted of simultaneous contractions of agonistic and antagonistic muscles at regular intervals and was generated by localized polyspike-wave activity in cortical primary motor areas. Activation of the STN did not appear to be an essential component of clonic seizures.
 ...
PMID:Electrophysiology of focal clonic seizures in humans: a study using subdural and depth electrodes. 1256 76

Lacosamide, an antiepileptic drug prescribed for children with refractory focal epilepsy, is generally well tolerated, with dose-dependent adverse effects. We describe 4 children who developed a movement disorder in conjunction with the initiation and/or uptitration of lacosamide. Three patients developed dyskinesias involving the face or upper extremity whereas the fourth had substantial worsening of chronic facial tics. The patients all had histories suggestive of opercular dysfunction: 3 had seizure semiologies including hypersalivation, facial and upper extremity clonus while the fourth underwent resection of polymicrogyria involving the opercula. Onset, severity, and resolution of dyskinesias correlated with lacosamide dosing. These cases suggest that pediatric patients with dysfunction of the opercular cortex are at increased risk for developing drug-induced dyskinesias on high-dose lacosamide therapy. Practitioners should be aware of this potential side effect and consider weaning lacosamide or video electroencephalography (EEG) for differential diagnosis, particularly in pediatric patients with underlying opercular dysfunction.
 ...
PMID:Lacosamide-Induced Dyskinesia in Children With Intractable Epilepsy. 3252 76