Long-Term Course of Childhood Epilepsy with Intractable Grand Mal Seizures

Abstract: Twenty-nine children with childhood epilepsy characterized by frequent grand mal (generalized tonic-clonic) seizures in spite of maximal doses of antiepileptic drugs and by an early onset of seizures (before 1 :year of age) were followed up for more than 5 :years. The children were divided into 3 :groups: severe myoclonic epilepsy in infancy (SME), no SME, and intractable childhood epilepsy with generalized tonic-clonic seizures (GTC). In all the 3 :groups, the grand mal seizures persisted, whereas the other types of seizures tended to disappear as the patients aged, and the prognosis for mental development was poor. In the majority of cases in all the 3 :groups, the waking grand mal seizures altered to sleep grand mal seizures with aging. Two pairs of monozygotic twins with SME suggested that genetic factors play a role in this epileptic syndrome. Intractable childhood epilepsy with GTC is distinguished by the absence of other types of generalized seizures. It cannot be regarded as an epileptic syndrome, but its pathogenesis and treatment require further studies.     

Gene Mapping in the Idiopathic Generalized Epilepsies: Juvenile Myoclonic Epilepsy, Childhood Absence Epilepsy, Epilepsy with Grand Mai Seizures, and Early Childhood Myoclonic Epilepsy

Summary: Idiopathic generalized epilepsies, i.e., juvenile myoclonic epilepsy (JME), childhood absence epilepsy, and epilepsy with grand mal [generalized tonic-clonic seizures (GTCS)], are the most common genetic epilepsies. Linkage studies using Bf, HLA serologic, and DNA markers by three independent investigators, one from Los Angeles and two from Berlin, have localized the JME locus to the short arm of chromosome 6 (6p). Because members of the same JME family have the same JME phenotype of childhood absence epilepsy, epilepsy with grand mal (GTCS) seizures, or early childhood myoclonic epilepsy (ECME), our observations give evidence for a single-locus etiology in 6p for JME and for at least some of the childhood absence seizures, epilepsy with grand mal (GTCS) seizures, and ECME. Studies should now address whether locus heterogeneity exists within childhood absence epilepsy, epilepsy with grand mal (GTCS) seizures, or ECME. Markers linked to JME (Bf, HLA serologic, and DNA markers in the DQ region) can be used to resolve etiologic heterogeneity. Using such markers, both linked and unlinked forms of phenotypes that are clinically indistinguishable may be detected and provide evidence for etiologic heterogeneity. Studies should also concentrate on narrowing the JME locus to 2 to 3 cm by screening families with recombinant events using RFLPs, candidate genes, and new expressed sequences on chromosome 6.     

Epilepsies with astatic seizures of late onset.

In 17 patients with a long course of epilepsy astatic seizures became apparent after the age of 14 years. In the patients' childhood astatic seizures had not been observed. The patients suffered from epilepsies with absences and awakening grand mal or psychomotor fits and sleeping grand mal. The EEG revealed spike-wave variant and spike-and-wave complexes as in the Lennox-Gastaut syndrome. Age dependency of Lennox-Gastaut syndrome is discussed. The described type of epilepsy can be understood as a "Lennox-Gastaut syndrome of late onset".     

TEMPORAL LOBE EPILEPSY

Types of seizures, age, at onset of epilepsy, preoperative duration of epilepsy, and age at operation were studied in the literature and in 74 patients who underwent unilateral temporal lobe resection in 1960–1969 in Denmark. the medical and surgical series were compared. the age at onset was significantly lower in the surgical series. Prognostically favourable factors were: i) preoperative presence of a single type of seizure; ii) duration of epilepsy of less than 4 years, and in grand mal epilepsy of less than 1 year; iii) operation for epilepsy in or before early adulthood. Prognostically unfavourable factors were: i) preoperative presence of grand mal; ii) age at onset of epilepsy or of the first grand mal seizure between 5 and 20 years; iii) preoperative duration of psychomotor epilepsy over 10 years.     

Longterm follow-up of childhood epilepsy with absences. II. Absence-epilepsy with initial grand mal

The study deals with 83 patients with absence epilepsy which had started with generalized tonic clonic seizures. Only those patients were included, who could be followed up to an age older than eighteen years. The patient population is heterogeneous; it includes numerous older patients in whom therapy had been instituted at a time when the present standard medication with ethosuximide and valproate was not available. Therefore the data cannot be used as a basis for global statements concerning the prognosis of absence epilepsy with grand mal onset. About 80% of the patients treated with standard therapy became seizure free. An unfavourable course was mainly preceded by incorrect, irregular and quantitatively inadequate therapy. Standard therapy cannot prevent singular generalised tonic clonic seizures in the late course. The social status of adult patients is mainly favourable if they are seizure free. Sporadic attacks usually will not impair social integration. In all, absence epilepsy starting with grand mal responds not as well to therapy and has a more unfavourable social prognosis than epilepsy starting with absences.     

Delayed diagnosis of juvenile myoclonic epilepsy.

Fifteen cases of juvenile myoclonic epilepsy (JME) were identified from one hundred and eighty consecutive patients referred to a new epilepsy clinic at St Thomas' Hospital between April 1989 and December 1990, a prevalence of 8.3%. Of these, only one was referred with a putative diagnosis of JME. Diagnosis of the other patients on referral included "epilepsy", "grand mal", "temporal lobe epilepsy", "photoconvulsive epilepsy" and "alcohol-induced epilepsy". At least 11 of the 15 patients had been seen by a neurologist in the United Kingdom before referral. Definitive diagnosis was delayed by a mean of 14.5 years. In seven patients inappropriate anticonvulsants had been prescribed. Control of seizures was improved in most patients after diagnosis. Factors responsible for the delay in diagnosis include lack of familiarity with the syndrome, failure to elicit a history of myoclonic jerking and high prevalence of focal abnormalities on the EEG. Precipitation of fits by alcohol and sleep deprivation may not be recognised by the physician as part of the syndrome of JME. Diagnosis may also be delayed in patients whose absence and generalised tonic-clonic seizures pre-date myoclonic jerks.     

Conversion of photosensitive to scotosensitive epilepsy: report of a case

A 13-year-old girl had had two grand mal attacks induced by viewing television when she was aged 10 and 11 years, and again a year later. Clinical and electroencephalographic (EEG) findings were typical of photosensitive television epilepsy. However, a further grand mal seizure when the patient was age 13 years occurred in darkness. Two additional EEG studies showed continuous paroxysmal activity during darkness. The epileptiform discharges were abolished by light and eye opening.     

Partial Epilepsy with Seizures Appearing in the First Three Years of Life

We reviewed records of 5,000 epileptic patients and identified 154 cases of partial epilepsy with seizure onset in the first 3 years of life. Of these, 35 patients had initial partial seizures. In 57 patients, partial seizures were preceded by a hemiclonic seizure, which manifested as status epilepticus in 70%. Generalized seizures were the initial manifestation in 62 patients: 17 grand mal, 14 clonic or myoclonic, and 31 tonic or atonic seizures. Of the 119 patients, 31 showed a seizure free-interval of several years between the initial seizure and the occurrence of partial epilepsy. The atypical initial clinical presentation and the seizure-free interval before occurrence of more characteristic partial seizures raise the possibility that the diagnosis of partial epilepsies in the first years of life may be missed.     

The use of relaxation training and a conditioned stimulus in the elimination of epileptic seizures in a child: A case study

Following systematic desensitization treatment for anxiety associated with recurrent seizures, a combination of relaxation training and association of a cue word with the calm body state was employed to eliminate seizures in a 12-yr-old boy with epilepsy. Following relaxation, the child was instructed to repeat the cue word several times so as to create a conditioned stimulus. After repeated pairings he was directed to verbalize the cue word to himself whenever he felt the aura of an approaching seizure. This resulted in avoidance of the onset of seizures and complete elimination of both grand mal and petit mal seizures. Long term follow-up showed no recurrence of seizures.     

Epilepsy in Ehlers-Danlos syndrome

PURPOSE: Ehlers-Danlos syndrome (EDS) is a complex hereditary connective tissue disorder infrequently reported in association with epilepsy. Seven patients with ages ranging from 28 to 70 years with EDS and epilepsy are described. METHODS: Case review of clinical and diagnostic data. RESULTS: Two patients had occipital horn syndrome (EDS type IX) and partial seizures of probable supplementary motor area origin. Of these two, one had an area of frontal gliosis and was able to abate his seizures by hyperextending his neck; the other had a Dandy Walker malformation and also had pseudoseizures. The third patient of the series had complex partial seizures, pain asymbolia, and basilar artery hypoplasia. The fourth had ictal aphasia, left hemispheric hypotrophy, and distal right arm and left leg atrophy. The fifth patient had focal seizures, a venous parietal angioma, hyperekplexia, nocturnal head oscillations (jactatio capitis nocturna), monoclonal gammopathy-associated neuropathy, and Tourette syndrome. The sixth had affective illness, chronic fatigue, and complex partial seizures with autoscopic phenomena after intracranial bleed. The seventh patient had a previous stroke, peripheral neuropathy, and grand mal seizures. CONCLUSIONS: EDS may be accompanied by congenital or acquired central nervous system disorders and epilepsy. Additional neurologic conditions that are unrelated to EDS may be present.     

Postictal blindness in adults.

Cortical blindness following grand mal seizures occurred in five adult patients. The causes of seizures included idiopathic epilepsy, vascular accident, brain cyst, acute encephalitis and chronic encephalitis. Blindness was permanent in one patients, but the others recovered within several days. Since most of the patients were either unaware of or denied their blindness, it is possible that this event often goes unrecognised. Cerebral hypoxia is considered the most likely mechanism.     

Serum prolactin and cortisol concentrations after grand mal seizures

Serial serum prolactin and cortisol levels were measured in five patients after a grand mal seizure and in four volunteers with simulated seizures. Single levels were measured after a witnessed seizure in 26 patients and in a matched control group. Significant increase in both prolactin and cortisol levels occurred after seizures. The change in cortisol level may reflect a non-specific stress response, but the increase in prolactin levels could not be accounted for on this basis, and probably indicates an alteration in hypothalamic neurotransmitter activity during the seizure. These findings may have clinical value in the diagnosis of epilepsy.     

Longterm follow-up of childhood epilepsy with absences. I. Epilepsy with absences at onset

The purpose of the follow-up study was to determine whether modern therapy with ethosuximide and/or valproate with/without phenobarbitone and its derivatives improves the longterm prognosis of absence epilepsy as compared to formerly used treatments. The patient population consisted of 194 cases (88 boys, 106 girls) with spike wave epilepsy starting with absences. In each case the diagnosis was confirmed by clinical observation and the typical EEG pattern. Only those patients were included who could be followed beyond the eighteenth year of life (up to age 45). The sample includes also older patients diagnosed during the fifties, before the present standard therapy was available. Because of the heterogeneity of the material and its selection, the data obtained are not suited to make a general statement about the ultimate prognosis of absences. The results demonstrate the effectiveness of regularly applied modern treatment. 72 out of 194 patients (37%) manifested generalized tonic clonic seizures (gtcs) during the course: 20 of these patients showed only incidental generalized tonic clonic seizures, which were not dependent on therapy. In 52 cases gtcs appeared without relation to precipitating factors. None of these patients received regular standard therapy before onset of gtcs. In 31 cases absence statuses were observed. These patients did not have an unfavourable outcome provided the standard therapy was instituted early and consequently. A change from absence epilepsy into an epilepsy with complex partial seizures sensu strictiori could not be observed. At final investigation 42 of 194 patients still had seizures: 7 with absences, 35 with grand mal with or without absences.(ABSTRACT TRUNCATED AT 250 WORDS)     

Psychogenic and physiological sequelae to hypnosis: two case reports

Two cases of hypnotic sequelae occurring in a research context (with a non-clinical college population) are reported. Case 1 was a male who experienced retroactive amnesia following hypnosis: He was unable to recall familiar telephone numbers later that day. This was not a continuation of an earlier confusion or drowsiness (as is often found) since he indicated he was wide awake following hypnosis. Two parallels exist with previous reports: unpleasant childhood experiences with chemical anesthesia and a conflict involving a wish to experience hypnosis but a reluctance to relinquish control. Case 2 was a female who, while in hypnosis, experienced an apparent epileptic seizure that had characteristics of both petit mal and grand mal seizures. Although having a history of epilepsy, she had not had a seizure in 7 years. We suspect that the seizure was psychogenic and may have been triggered by wording used in the hypnotic scale or other similarities. Possible mechanisms are discussed and preventative recommendations are made.     

PLASMA LEVEL AND EFFECT OF CARBAMAZEPINE IN GRAND MAL AND PSYCHOMOTOR EPILEPSY

In 117 patients with grand mal and psychomotor epilepsy the effect of carbamazepine alone or in combination with phenobarbital and diphenylhydantoin was registered and correlated to the plasma level of carbamazepine.
Carbamazepine was found to be an effective anticonvulsant in the treatment of grand mal epilepsy. The therapeutic level was higher than 4 mg/l.
Carbamazepine given alone was rather ineffective in the treatment of psychomotor seizures.
The concentration of plasma carbamazepine epoxide, one of the metabolites of carbamazepine, was increased when the patients were treated with carbamazepine, in combination with phenobarbital or diphenylhydantoin or both. This may explain the better clinical effect of this combined medication, as the epoxide has an independent antiepileptic effect. The side-effects may be partly caused by the epoxide.     

无神经系统定位体征的癲癇大发作患者的EEG和CT分析

目的探讨无神经系统定位体征的癲癇大发作患者的脑电图(EEG)和脑CT变化.方法 68例无神经系统定位体征的癲癇大发作患者作EEG 及脑CT检查.结果 EEG异常率为82.35%,CT异常率为32.35%.CT正常组和异常组中,EEG异常率无明显差异.CT异常率与病程关系不大,但有发病诱因的继发性癲癇CT异常率较无明显原因者显著增高.结论 EEG为癲癇诊断的重要电生理检查方法,且有粗略定位意义,而CT能显示脑结构方面的病理改变,有利于查找病因及病变部位.     

Epileptic seizures in the 4p- syndrome: report of two cases.

We report ictal phenomena in two patients with the 4p- syndrome captured on simultaneous video-EEG monitor. One patient, diagnosed as having partial epilepsy, had complex partial seizures and hemiconvulsive status epilepticus. This was associated with more severe mental retardation. The second patient was diagnosed as having the West syndrome and exhibited tonic spasms with a cluster formation. We conclude that various types of epileptic seizures may occur in patients with the 4p- syndrome, including grand mal and myoclonic seizures.     

Epileptic Seizures in the 4p- Syndrome: Report of Two Cases

Abstract: We report ictal phenomena in two patients with the 4p – syndrome captured on simultaneous video-EEG monitor. One patient, diagnosed as having partial epilepsy, had complex partial seizures and hemiconvulsive status epilepticus. This was associated with more severe mental retardation. The second patient was diagnosed as having the West syndrome and exhibited tonic spasms with a cluster formation. We conclude that various types of epileptic seizures may occur in patients with the 4p - syndrome, including grand mal and myoclonic seizures.     

Electroencephalographic Manifestations of Grand Mai Epilepsy in Africans: Observation of Relative Rarity of Interictal Abnormalities

Interictal EEG records of Nigerian epileptic patients living in Lagos and clearly diagnosed as having grand mal epilepsy were compared with those of British epileptic patients with a similar diagnosis. Interictal EEG abnormalities (spike and wave discharges, (SW), photoparoxysmal discharges (PPD), and nonspecific changes) were significantly less common in Nigerian patients (incidence 15.7%) compared with British patients (incidence 52.9%) irrespective of age or sex of the patients. These findings may be related to ethnic or geographical factors. Rarity of PPD in Africans has previously been attributed to ethnic factors. Other studies have demonstrated an influence of geographical factors, specifically sunshine. In papio papio, such a geographical factor was shown to influence occurrence of PPD. In human epileptic subjects, environmental sunshine has been found to inversely influence the occurrence of PPD as well as SW. Besides possible ethnic factors, the relative rarity of interictal EEG abnormalities in Africans with grand mal epilepsy may be related to the larger amount of sunshine in the tropics.     

Molecular genetics of epilepsy]

Recent identifications of genes responsible for epilepsies are now contributing to diagnosis and treatment. Mutations of voltage-gated sodium channel genes SCN1A and SCN2A have been reported in epilepsies with a variety of phenotypes including generalized epilepsy with febrile seizures plus (GEFS +), severe myoclonic epilepsy in infancy (SMEI), intractable childhood epilepsy with generalized tonic-clonic seizures (ICEGTC), and benign familial neonatal-infantile seizures (BFNIS). We also identified a sporadic nonsense mutation of SCN2A in a patient with intractable epilepsy with severe mental decline. Lafora's disease (LD) is a fatal autosomal recessive epilepsy characterized by stimuli sensitive myoclonus, grand mal seizures, and progressive intellectual and neurological deterioration. The EPM2A gene has been reported to be responsible for LD. We found multiple disease mutations of EPM2A in LD patients, and also identified a subclass of LD who shows an early onset cognitive defect and correlated with EPM2A exon 1 mutations. We reported that the laforin protein encoded by the EPM2A gene has a dual-specificity phosphatase activity, associates with polyribosome, and interacts with the HIRIP5 protein with NifU-like domain. We recently generated and reported the EPM2A KO mice those develop neurodegeneration and other features similar to those of LD patients.