Diffuse Slow Spike-waves Research Articles

Acquired cognitive dysfunction with focal sleep spiking activity

The syndrome of continuous spike-waves during slow sleep (CSWS) is considered an epileptic encephalopathy in which the epileptiform abnormalities may contribute to progressive cognitive dysfunction. The characteristic electroencephalographic feature of the syndrome occurs during non-REM sleep, and takes the form of continuous bilateral and diffuse slow spike-waves that persist through all slow sleep stages. Using a case study design including clinical, neuropsychological, electroencephalographic, and positron emission tomography with 18F-fluorodeoxyglucose (PET-FDG) investigations, we describe the clinical and electroencephalographic findings in two patients who presented with nonsymptomatic epilepsy with unilateral spike-waves during sleep. Both patients presented with a left unilateral motor neglect of the upper limb that was associated with unilateral CSWS activity over the right hemisphere, predominantly in the centrotemporal region. PET-FDG studies during the active phase of CSWS showed right centrotemporal hypermetabolism in both cases. After treatment, a regression of the CSWS activity and an improvement of the cerebral FDG pattern were paralleled by a remission of the motor neglect. These cases demonstrate that the electroencephalographic pattern of CSWS in nonsymptomatic epilepsies is not necessarily diffuse and bilateral, and that focal unilateral CSWS activity can be associated with focal neuropsychological deficits. These findings add further evidence that the spectrum of clinical conditions associated with the electroencephalographic pattern of CSWS can include different forms of acquired cognitive disturbances that may be focal in nature.

Free Communications: Child

Abstract *YokoOhtsuka, *HodakaOhta, *MikiInutsuka, *KatsuhiroKobayashi, *HarumiYoshinaga, and *EijiOka *Department of Child Neurology, Okayama University Medical School, Okayama, Japan Purpose: To investigate the electroclinical characteristics and treatment of generalized nonconvulsive status epilepticus (NCSE) in childhood. Methods: The subjects were 21 children whose clinical manifestations and EEGs during NCSE were thoroughly analyzed by simultaneous video-EEG-EMG polygraphic recordings. They consisted of seven patients with Lennox–Gastaut syndrome or other generalized epilepsies (group A), 10 patients with myoclonic epilepsies such as Doose syndrome (group B), and four patients with partial epilepsies who transiently showed atypical absence status during their clinical course (group C). We excluded NCSE observed in some specific epileptic syndromes such as severe myoclonic epilepsy in infancy, epilepsy with continuous spike–waves during slow-wave sleep, and related epilepsies. Results: During NCSE, all patients showed decreased alertness or reactivity. Disturbance of mental activity and/or ataxia also was seen in many cases. In addition to these persistent symptoms, all patients showed frequent seizures during NCSE, such as atypical absences, myoclonic seizures, and negative myoclonus. Atypical absences were often seen in all groups of patients. Myoclonic seizures were seen in almost all patients in group B but were rarely seen in groups A and C. EEGs during NCSE were classified into three types: (a) diffuse slow spike–waves, diffuse fast spike–waves and/or diffuse polyspikes–waves intermixed with high-voltage slow waves (SPW type); (b) diffuse high-voltage slow waves intermixed with short bursts of spike–waves (HVS type); and (c) an extremely disorganized pattern in which high-voltage slow waves and seizure discharges were haphazardly intermingled (disorganized type). SPW type was often seen in group A, and HVS type was often seen in group B. Disorganized type was sometimes seen in groups A and B, but no patient in group C showed this type. Regarding treatment, intravenous injections of diazepam (DZP) were tried in almost all patients and were effective on most occasions. However, their effect usually was only transient. We investigated treatments that had more persistent effects for the termination of NCSE. Valproate (VPA) was effective in 10 (50%) of 20 patients; ethosuximide (ESM), in seven (87.5%) of eight; benzodiazepines (BZDs) in six (40%) of 15; and synthetic adrenocorticotropic hormone (ACTH) therapy in four of four patients. ESM was used in combination with VPA in all seven ESM-responsive patients. In two of them, both ESM and VPA were indispensable. In the others, ESM was added to the ineffective previously administered antiepileptic drugs (AEDs) including VPA, and VPA could be decreased thereafter. Conversely, in 14 of 21 patients, simplification of AED therapy seemed to have a favorable effect. Discontinuation or decrease of BZDs was effective in five patients, carbamazepine (CBZ) in four, phenobarbital (PB) and phenytoin (PHT) in three each, and primidone (PRM) and acetazolamide in two each. We also analyzed the relation between seizure type and treatment effect and also the relation between EEG type and treatment effect. Among 16 patients who had atypical absences during NCSE, ESM was effective in six of seven, VPA in seven in 15, BZDs in four of 12, and synthetic ACTH in three of three. Among the 12 patients who showed SPW-type EEGs, ESM was effective in six of seven patients, VPA in four of 12, BZDs in three of nine, and synthetic ACTH in three of three. Among the six patients who showed HVS-type EEGs, VPA was effective in five of five patients and BZDs in two of four. Conclusions: Generalized NCSE observed in various types of childhood epilepsies shared similar clinical and EEG manifestations. ESM was often effective in patients who had atypical absences and SPW-type EEGs. VPA was often effective in patients who had HVS-type EEGs. Simplification of AEDs had a favorable effect in all groups of patients.

Topiramate in the catastrophic epilepsies of childhood.

Several epileptic syndromes that occur during childhood are characterized by severe treatment-resistant seizures, progressive loss of higher intellectual functions, and characteristic electroencephalographic abnormalities. These catastrophic epileptic syndromes include epileptic encephalopathy with diffuse slow spike waves (Lennox-Gastaut syndrome), West syndrome, progressive myoclonic epilepsies, and electrical status epilepticus during sleep. This article summarizes each syndrome and reviews the most recent information concerning the effectiveness of topiramate with respect to each condition. Suggestions are offered to help clinicians maximize topiramate's efficacy and tolerability in patients suffering with these syndromes. Overall, topiramate is a valuable antiepileptic medication in the treatment of catastrophic pediatric epileptic syndromes.

Combination Treatment of High‐Dose Pyridoxal Phosphate and Low‐Dose ACTH in Children with West Syndrome and Related Disorders

Combination therapy of high-dose pyridoxal phosphate (PAL-P, 40-50 mg/kg/day) and low-dose ACTH beta 1-24-Z (tetracosactide acetate-Zn, Cortrosyn Z, 0.01 mg/kg/day) was instituted in 26 children suffering from West syndrome and related disorders--pretreated without success with high-dose PAL-P alone; 18 with West syndrome (14 with symptomatic and 4 with cryptogenic types), 2 with symptomatic Lennox-Gastaut syndrome, 5 with cerebral palsy with hypsarhythmia or diffuse slow spike-waves and one with myoclonic seizures (secondary generalized epilepsy). Clinical, electroencephalographic and neurochemical investigations were carried out. The results were summarized as follows. 1) Only one of 27 children with West syndrome and related disorders pretreated using high-dose PAL-P alone before ACTH showed a clinically excellent response. 2) Clinical seizures were completely suppressed in 19 of 21 children who initially had seizures (90%) after this combination therapy. 3) Twenty-one of the total 26 children (80%) had disappearance of hypsarhythmia or diffuse slow spike-waves in EEG after this therapy. 4) During PAL-P treatment alone transient increases in liver enzymes occurred in 37 percent. The brain shrinkage of CT and the significant rise in CSF NSE were seen in 95% and 78% after ACTH, respectively. 5) Twenty-three children have been followed for one to 29 months after tapering off of ACTH. No relapses were experienced in 11 of 18 who initially had seizures (61%) and 13 of 23 with hypsarhythmia or diffuse slow spike-waves (57%). 6) Postictal PRL elevations were suppressed during high-dose PAL-P. 7) No significant changes in the CSF levels of HVA and 5-HIAA were seen during this combination therapy. The CSF levels of HVA were significantly lower than the controls. 8) Daily ACTH therapy transiently suppressed the secretion of anterior pituitary hormones (GH, TSH, PRL, LH and FSH) and thyroid hormones (T3 free T3, T4 and free T4). It is recommended that the combination therapy of high-dose PAL-P and low-dose ACTH is a promising new method and should be tried in children with West syndrome and related disorders. The mechanism of action of this combination therapy remains obscure although some information has been obtained from our investigations.

Long‐Term Prognosis of the Lennox‐Gastaut Syndrome

A long-term follow-up study of 89 patients of Lennox-Gastaut syndrome (LGS) disclosed the persistent occurrence of seizures in 68 patients (76.4%) and severe mental defect in 48 (53.9%). An analysis of the correlation between the mental and seizure prognoses confirmed that the persistence of minor seizures could result in mental deterioration. An examination of the evolutional changes in EEG demonstrated that diffuse slow spike-waves characteristic of LGS gradually disappeared, while focal epileptic discharges, especially multifocal spikes, appeared in spite of the persistence of minor seizures. The diagnostic criteria were satisfied in only 31 (47.0%) of 66 patients with the persistence of minor seizures. Patients with multiple independent spike foci and minor seizures were considered to belong to a specific type of epilepsy, namely the severe epilepsy with multiple independent spike foci (the severe epilepsy with MISF). The seizure and mental prognoses were poorer in patients who evolved into the severe epilepsy with MISF than others.

Combined myoclonic-astatic and "benign" focal epilepsy of childhood ("atypical benign partial epilepsy of childhood"). A separate syndrome?

The authors have followed six children with atypical epilepsies but a favorable evolution, consisting in minor motor seizures of the myoclonic-astatic type (with diffuse slow spike-waves on the electroencephalogram) together with clinical and EEG features seen in benign focal epilepsy of childhood (BFEC), an association recently reported by Aicardi and Chevrie (1982). The maintenance of a normal neurological function despite severe epilepsy, the absence of tonic seizures and the marked activation of the spike discharges during sleep were described by these authors as important characteristics suggesting a good prognosis. The purpose of this study was to see if these children indeed represent a particular subgroup of idiopathic epilepsy and to draw attention to a special clinical and EEG combination indicating a possibly favorable ultimate outcome, in children usually diagnosed as suffering from Lennox-Gastaut syndrome. The six cases closely resembled the group described by Aicardi and Chevrie (1982), although the clinical and EEG features of BFEC were not as striking as in their cases. Also transient mental deterioration occurred during the active seizure periods. The therapeutic benefit of the various drugs tried was difficult to assess, but the behavior was often perturbed by medication. Although it is not possible to decide at the present time if these cases represent a particular epileptic syndrome, the special combination of clinical and EEG features seems characteristic enough to justify prospective studies of similar cases in the future.

Complex partial seizures in childhood.

A clinical and electroencephalographic study was undertaken on 215 children with complex partial seizures as selected on the basis of the International Classification of Epileptic Seizures (1981). Complex partial seizures were noted in 7.8% of the epileptic children. The ictal symptoms of complex partial seizures closely resembled those of psychomotor triad described by Lennox. Interictal EEG revealed seizure discharges from the temporal or frontal focus in 57.2%. There existed a group with automatism as a main symptom having both diffuse slow spike-waves and focal temporal spikes. This type should be interpreted to be one of secondary generalized epilepsies and be a variant of the Lennox syndrome.

Seizure disorders in infancy and childhood

Of various topics concerning convulsive disorders in children, long-term prognosis of childhood epilepsy and developmental aspects of age-dependent epileptic encephalopathy (ADEE) were described. Recent progress in epileptology and introduction of effective antiepileptic drugs has allowed marked improvement in the prognosis of epilepsy. According to our long-term observation of epileptic children over 10 years, the remission rate for over three years was as high as 81.7%. Intractable cases were notably high in the West and Lennox syndromes. One of the main targets of child epileptology is ADEE, i.e. the West and Lennox syndromes in addition to early-infantile epileptic encephalopathy with suppression-burst (EIEE). The concept and categorization of ADEE were outlined with special reference to the developmental aspects of EIEE by a long-term follow-up study. Six of 10 cases of EIEE evolved into the West syndrome at two to six months of age, and two cases showed further transition to the Lennox syndrome at one year one month and three years one month of age. In accordance with the evolutional change in clinical seizure pattern, EEG showed an evolutional change from suppression-burst to hypsarhythmia and further development to diffuse slow spike-waves. These facts suggest a close relationship among these three types of ADEE and the significance of developmental aspects in the study of epilepsy.

Psychotic Symptoms in Childhood Epilepsy –An Electroencephalographic Study–

To investigate the significance of EEG findings relating to the appearance of psychic symptoms in epileptic children, a clinicoelectroencephalographic study was undertaken on 15 cases with psychotic episodes. 1) Psychotic episodes with hallucination and/or illusion were observed, though rarely, in childhood epilepsy. These seemed liable to occur in temporal lobe epilepsy. 2) Three of four patients in the hallucination and illusion group showed frequent epileptic discharges. However, no distinct relation existed between seizure discharges and psychotic episodes. 3) Eight of 11 patients in the dysphoria and excitement group were secondary generalized epilepsy. 4) In the dysphoria and excitement group, psychotic episodes occurred either as a result of the increase in epileptic discharges or conversely as a result of the suppression of epileptic discharges. The former was more frequent. Epileptic discharges tended to be suppressed in the Lennox syndrome and allied conditions relating to psychotic episodes. 5) A forced normalization-like phenomenon mostly resulted from the marked suppression of diffuse slow spike-waves. However, a complete suppression of epileptic discharges was not always noted.

Age-dependent epileptic encephalopathy: a longitudinal study.

A longitudinal clinico-electroencephalographic study was conducted on 484 cases of age-dependent epileptic encephalopathy; early-infantile epileptic encephalopathy with suppression-burst (Ohtahara) (EIEE), the West and Lennox syndromes. 1) The three types had the same kind of etiologic heterogeneity. 2) An evolutional change with age was noted from EIEE to the West and from the West to the Lennox syndromes, with the change from suppression-burst to hypsarhythmia, and from hypsarhythmia to the diffuse slow spike-waves. 3) The core ictal EEG pattern of tonic spasms was the desynchronization in EIEE and the West syndrome, with the rapid synchronization and recruiting rhythm in the Lennox syndrome. In the same cases, the changes from desynchronization to hypersynchronization were observed with age. These facts suggest that the three syndromes are based on the same pathophysiology, strongly related to the subcortical mechanism, and that their clinico-electrical manifestations are modified by the degree of brain maturation.

Treatment of the lennox syndrome with ACTH: A clinical and electroencephalographic study

In 45 cases of Lennox syndrome treated with ACTH, the immediate and long-term effects and the various factors affecting them were investigated by a follow-up study. 1) Regarding the immediate effect, 23 (51.1%) of the 45 cases became "seizure free" for over 10 days. 2) As to the long-term prognosis of these 23 cases, 10 cases relapsed into Lennox syndrome within 6 months and in the remaining 13 cases, seizures were suppressed for over 6 months; out of these 13, seizure relapse was observed in eight cases from 9 months to 7 years later, and the other five cases followed a very favorable course without relapse. 3) The favorable factors related to the effect of ACTH for Lennox syndrome are: a) age at ACTH treatment: up to 4 years old, b) time lag between onset of Lennox syndrome and initiation of ACTH treatment: the shorter the better; at least within 1 year, preferably within 3 months, c) presumptive causes and underlying diseases: idiopathic cases are best, d) mental defects before treatment: the slighter the better, e) seizure patterns: without tonic seizures, and f) EEG findings: disorganized diffuse slow spike-waves without asymmetry. 4) It is desirable to continue the ACTH treatment as long as possible, with the goal of the disappearance of seizure discharges, or at least the disappearance of diffuse seizure discharges.

Bissincronia secundária na síndrome de Lennox

Foram estudadas as relações entre lesões convulsiógenas focais não temporais e encefalopatías epilépticas da criança com ponta-ondas lentas difusas. De 32 pacientes com características clínicas e/ou EEG de síndrome de Lennox submetidos a seguimentos clínico-terapéuticos e EEG longitudinais foram selecionados 11 (3 com sinais clínicos e EEG de comprometimento cortical mesial e 8 com sinais de lesão difusa num dos hemisférios). A história clínica, os achados do exame neurológico e anormalidades EEG focais têm importância quanto à localização primitiva da agressão cerebral. Não há dados fisiopatogênicos seguros para excluir da síndrome de Lennox as seqüelas de encefalopatia mioclônica infantil com hipsarritmia, os casos com sinais clínicos e/ou EEG de localização cortical ou hemisférica, desde que sejam observadas as alterações EEG bissíncronas secundárias e clínicas características bem como a peculiar resposta terapêutica.

Emprego de mogadon endovenoso em pacientes epilépticos: estudo clínico e eletrencefalográfico

Mogadon endovenoso foi administrado a 12 pacientes com manifestações epilépticas freqüentes e/ou prolongadas, a 6 pacientes com encefalopatía epiléptica infantil com ponta-ondas difusas e a dois com epilepsia fotossensível. A droga mostrou-se eficaz no controle clínico e eletrencefalográfico dos diferentes tipos de crises em 11 dos 12 primeiros doentes, no controle clínico e eletrencefalográfico de 3 dos 6 pacientes com síndrome de Lennox e no controle das manifestações clínicas e eletrencefalográficas espontâneas e desencadeadas pela SLI nos dois últimos. O estudo limitou-se a pacientes com afecção cerebral crônica, desde que o mais freqüente efeito colateral da droga foi soñolencia. Os efeitos clínicos e eletrencefalográficos foram semelhantes àqueles obtidos com a administração parenteral do Valium. Aspectos particulares quanto à ação desta substância na síndrome de Lennox foram discutidos.