A Psychosocial Approach to Epileptic Patients

Summary: A psychoeducational approach was taken with 174 epileptic patients. Using this approach, no family problems were recognized among patients with idiopathic generalized epilepsy (IGE) or among those with symptomatic generalized epilepsy (SGE). However, 11 patients with temporal lobe epilepsy (TLE) and 1 patient with non-temporal lobe epilepsy (non-TLE) did exhibit family problems indicating that such problems involving IGE or SGE cases can be prevented through educational programs using a psychoeducational approach. This fails, however, to prevent such problems for TLE or non-TLE cases. Furthermore, small group psychotherapy was given to 10 patients with intractable TLE. They were directed to make self-evaluations regarding therapeutic factors originally introduced by Yalom but specially modified for these particular patients. Relatively high evaluations were given on every factor when compared with the results of individual psychotherapy. These results point out the importance of providing such psychotherapeutic approaches as group psychotherapy and self-help groups in addition to educational programs in order to enhance the quality of life (QOL) of epileptic patients and their families.     

苯妥英治疗癫痫发作的有效血浓度的探讨

本文用紫外分光亮度法测定了５８例癫痫病人的苯妥英的有效血浓度，并进行了随访观察。结果显示：苯妥英的有效血浓度为９．６６±６．１１ｍｇ／Ｌ。本文讨论了发作类型对苯妥英的有效血浓度的影响以及成年患者口服苯妥英的起始剂量、有效血浓度与发作间期脑电图和癫痫复发的关系等问题，并提出了建立稳态警界值浓度的可行性。     

Natural History of Epileptic Seizures

Since 1963 a continuous registration of patients with epileptic seizures has been carried out in Greater Aarhus, Denmark. This registration has been attempted by means of medical records dating back to 1940. On the basis of the established prevalence and the calculated cumulated incidence, we have tried to describe the natural history of the different types of epilepsy. The prevalence of all types of epileptic seizures (including febrile convulsions) has been found to be 2,441/100,000, whereas for patients with the diagnosis of epilepsy the rate is 1,274/100,000. The study describes the natural history of the different types of epilepsy. In addition, the risk-increasing effect of a febrile convulsive seizure on the development of epilepsy is analyzed.     

Somatostatin-Positive Interneurons Contribute to Seizures in SCN8A Epileptic Encephalopathy

SCN8A epileptic encephalopathy is a devastating epilepsy syndrome caused by mutant SCN8A, which encodes the voltage-gated sodium channel Na_V1.6. To date, it is unclear if and how inhibitory interneurons, which express Na_V1.6, influence disease pathology. Using both sexes of a transgenic mouse model of SCN8A epileptic encephalopathy, we found that selective expression of the R1872W SCN8A mutation in somatostatin (SST) interneurons was sufficient to convey susceptibility to audiogenic seizures. Patch-clamp electrophysiology experiments revealed that SST interneurons from mutant mice were hyperexcitable but hypersensitive to action potential failure via depolarization block under normal and seizure-like conditions. Remarkably, GqDREADD-mediated activation of WT SST interneurons resulted in prolonged electrographic seizures and was accompanied by SST hyperexcitability and depolarization block. Aberrantly large persistent sodium currents, a hallmark of SCN8A mutations, were observed and were found to contribute directly to aberrant SST physiology in computational modeling and pharmacological experiments. These novel findings demonstrate a critical and previously unidentified contribution of SST interneurons to seizure generation not only in SCN8A epileptic encephalopathy, but epilepsy in general.SIGNIFICANCE STATEMENT SCN8A epileptic encephalopathy is a devastating neurological disorder that results from de novo mutations in the sodium channel isoform Na_v1.6. Inhibitory neurons express Na_V1.6, yet their contribution to seizure generation in SCN8A epileptic encephalopathy has not been determined. We show that mice expressing a human-derived SCN8A variant (R1872W) selectively in somatostatin (SST) interneurons have audiogenic seizures. Physiological recordings from SST interneurons show that SCN8A mutations lead to an elevated persistent sodium current which drives initial hyperexcitability, followed by premature action potential failure because of depolarization block. Furthermore, chemogenetic activation of WT SST interneurons leads to audiogenic seizure activity. These findings provide new insight into the importance of SST inhibitory interneurons in seizure initiation, not only in SCN8A epileptic encephalopathy, but for epilepsy broadly.     

Epileptic Seizures in AD Patients

Epileptic seizures have long been recognised as a complication of the clinical syndrome of Alzheimer’s disease, particularly in advanced disease, but have hitherto been viewed essentially as epiphenomena of the neurodegenerative process. Progress with animal models of Alzheimer’s disease has suggested that this view may be incorrect, and that seizures may be a reflection of pathophysiological processes similar to or overlapping with those responsible for cognitive decline. This overlap between neuropsychological and neurophysiological changes suggests that seizures in Alzheimer’s disease may be a valid therapeutic target, over and above symptomatic treatment. This article reviews data on the prevalence of seizures in Alzheimer’s disease, seizure types, pathophysiology and treatment. Seizure prevalence increases with disease duration, but early-onset disease is associated with a greater risk of seizures, in part related to the frequency of presenilin-1 gene mutations in early-onset disease. Seizures are mostly of partial origin, with both complex partial and secondary generalised seizures. Seizure pathophysiology may relate to increased amyloid beta-peptide production, structural alterations in neurones related to cytoskeletal dysfunction, cerebrovascular changes, neurotransmitter dysfunction or combinations thereof. Through modification of these pathophysiological pathways, there may be possible roles for anti-epileptic drugs such as sodium valproate and lacosamide in the treatment of Alzheimer’s disease. In summary, epileptic seizures are part of the AD phenotype, and merit further investigation.     

Compulsive Somatosensory Self-Stimulation Inducing Epileptic Seizures

Three children who had been diagnosed as having infantile spasms with major psychomotor retardation were referred for the persistence of series of spasm-like seizures, which were resistant to antiepileptic drug treatment, beyond infancy. Serial seizures were elicited by a compulsive self-stimulating behavior that was documented by long-term video-polygraphy. These behaviors implicated proprioceptive inputs: tapping on the chin in one case, flexion and external rotation of the leg with dislocation of the femur in one case, a particular posturing of the body followed by rhythmic shaking of the head in the last case. This clinical picture seems to constitute a particular type of outcome for infantile spasms and is particularly resistant to therapy.     

A Tautology in the Classification of Generalized Non-Convulsive Epileptic Seizures

Five patients with the Lennox-Gastaut syndrome who have shown generalized non-convulsive seizures were presented. The seizure manifestations which occurred spontaneously were documented by simultaneous recording and analyzed in terms of clinical and electroencephalographic correlates. According to the diagnostic criteria of the International Classification,² it was possible, on the one hand, to regard them as "atypical complex absences" in which the impairment of consciousness is accompanied by other symptoms, which tend to dominate the clinical picture. They were: hypotonic, hepertonic, myoclonic and akinetic components, respectively.
On the other hand, if we give a special weight to the accompanying symptoms, it is entirely possible that they are at the same time diagnosed atonic, axial tonic, bilateral myoclonic and akinetic seizures. The initial impairment of consciousness is common to all the seizure manifestations, and the ictal and interictal EEG expressions are not of diagnostic significance.
A question arises as to whether two different nomenclatures were arbitrarily given to a unique ictal manifestation or not as far as the generalized non-convulsive seizures were concerned.     

Postictal SPECT in Epileptic Versus Nonepileptic Seizures

Despite advances in video-electroencephalogram (EEG) technology, in many patients distinguishing epileptic seizures from nonepileptic seizures (NES) remains a challenge. Reliable methods to make this distinction are needed. In a pilot study, we performed postictal and interictal single photon emission computed tomography (SPECT) in 22 patients undergoing video-EEG monitoring who had altered responsiveness during an episode. Eleven had seizures, defined as episodes associated with EEG seizure patterns or postictal prolactin (PRL) elevations greater than 1.5 times the highest interictal baseline PRL; 11 had NES. Among the 11 seizures, postictal SPECT was abnormal in seven (regions of hypoperfusion in six and hyperperfusion in one) and normal in four. In six cases (55%), the interictal and postictal SPECT changed. Among the 11 NES cases, postictal SPECT was abnormal in three cases (all hypoperfusion abnormalities) and normal in eight cases. In no case did the interictal and postictal SPECT change. This small sample revealed a trend toward greater hypometabolism (postictal versus interictal) on SPECT for epileptic seizures compared to NES (p < 0.12). There were postictal SPECT changes in two of five seizures unassociated with postictal PRL elevation. Prolactin was elevated in two cases unassociated with change on SPECT. Comparision of postictal to interictal SPECT may help distinguish epileptic seizures from NES. Results from SPECT may also help identify epileptic seizures unassociated with PRL elevation.     

Epileptic Seizures in Elderly Patients with Dementia

All inpatients aged greater than 55 years with dementia in the Dundee Psychiatric Service were surveyed for seizure occurrence by interviewing staff and reviewing records. Of 208 patients, 19 (9.1%) were recorded as having seizures. The seizures were major in 92% and occurred at a rate of approximately 2.3 seizures per patient per year. Patients with epilepsy were significantly younger than a control group of dementia inpatients and were significantly more cognitively impaired on the survey Clifton Assessment Procedure for the Elderly (CAPE), but not on the Mini Mental State Examination. Of 111 reported accidents, only 5 appeared to be associated with epilepsy. Although epileptic seizures are relatively common in patients with severe dementia, they rarely caused severe problems.