SUMMARYPurpose: Current treatments for epilepsy may control seizures, but have no known effects on the underlying disease. We sought to determine whether early treatment in a model of genetic epilepsy would reduce the severity of the epilepsy phenotype in adulthood. Methods: We used Wistar albino Glaxo rats of Rijswijk (WAG/Rij) rats, an established model of human absence epilepsy. Oral ethosuximide was given from age p21 to 5 months, covering the usual period in which seizures develop in this model (age ∼3 months). Two experiments were performed: (1) cortical expression of ion channels Nav1.1, Nav1.6, and HCN1 (previously shown to be dysregulated in WAG/Rij) measured by immunocytochemistry in adult treated rats; and (2) electroencephalogram (EEG) recordings to measure seizure severity at serial time points after stopping the treatment.Results: Early treatment with ethosuximide blocked changes in the expression of ion channels Nav1.1, Nav1.6, and HCN1 normally associated with epilepsy in this model. In addition, the treatment led to a persistent suppression of seizures, even after therapy was discontinued. Thus, animals treated with ethosuximide from age p21 to 5 months still had a marked suppression of seizures at age 8 months. Discussion: These findings suggest that early treatment during development may provide a new strategy for preventing epilepsy in susceptible individuals. If confirmed with other drugs and epilepsy paradigms, the availability of a model in which epileptogenesis can be controlled has important implications both for future basic studies, and human therapeutic trials.

Overall, the beneficial effect from chronic stimulation in our series persisted in more than half of the patients for whom procedure was considered and in 80% of those who significantly improved during the trial and proceeded with internalization. Thus, chronic PNS may be a safe and relatively effective method for long-term treatment of chronic pain syndrome in patients with medically intractable ON.

Summary:Generalized epileptic seizures produce widespread physiological changes in the brain. Recent studies suggest that "generalized" seizures may not involve the whole brain homogeneously. For example, electrophysiological recordings in WAG/Rij rats, an established model of human absence seizures, have shown that spike-and-wave discharges are most intense in the perioral somatosensory cortex and thalamus, but spare the occipital cortex. Is this heterogeneous increased neuronal activity matched by changes in local cerebral blood flow sufficient to meet or exceed cerebral oxygen consumption? To investigate this, we performed blood oxygen level-dependent functional magnetic resonance imaging (fMRI) measurements at 7T with simultaneous electroencephalogram recordings. During spontaneous spike-wave seizures in WAG/Rij rats under fentanyl-haloperidol anesthesia, we found increased fMRI signals in focal regions including the perioral somatosensory cortex, known to be intensely involved during seizures, whereas the occipital cortex was spared. For comparison, we also studied bicuculline-induced generalized tonic-clonic seizures under the same conditions, and found fMRI increases to be larger and more widespread than during spike-and-wave seizures. These findings suggest that even in regions with intense neuronal activity during epileptic seizures, oxygen delivery exceeds metabolic needs, enabling fMRI to be used for investigation of dynamic cortical and subcortical network involvement in this disorder.

Object Treatment of chronic neuropathic pain in the region of the head and face presents a challenge for pain specialists; patients who do not respond to conventional treatment modalities usually continue to suffer from pain due to the lack of reliable medical and surgical approaches. Peripheral nerve stimulation (PNS) has been used to treat neuropathic pain for many decades, but only recently has it been applied systematically to the craniofacial region. To advance the study of this treatment option, the authors present their initial experience with this approach, summarize published data on the use of PNS in treatment of craniofacial pain, and discuss some technical details of the craniofacial PNS procedure. Methods A review of prospectively collected data in 30 patients who underwent PNS surgery for craniofacial pain was performed. The pain location, duration, cause, and previous treatments were analyzed, along with the surgical details, initial and long-term results, complications, and repeated operations. Stimulated nerves in this group included supraorbital (seven patients), infraorbital (six), and occipital (21); in 19 patients more than one nerve was stimulated. Twenty-two patients proceeded with implantation of a permanent system after the trial. Of these, at the time of the latest evaluation (mean follow-up duration 35 months), in two patients the devices had been removed because of pain improvement over time, in three the devices were removed due to loss of effectiveness (two cases) or late infection (one), and the rest are enjoying either complete (15 patients) or partial (two patients) pain relief. Three patients underwent repeated operation due to lead erosion, infection, or migration. Conclusions Peripheral nerve stimulation appears to be a safe and effective approach in the treatment of craniofacial neuropathic pain. The growing body of literature supports a wider acceptance of this approach in the field of pain surgery.