A new method for quantification and assessment of epileptiform activity in EEG with special reference to focal nocturnal epileptiform activity.

Quantification of epileptiform activity in EEG has been applied for decades. This has mainly been done by visual inspection of the recorded EEG. There have been many attempts using computers to quantify the activity, usually with moderate success. In a row of contexts, including Landau-Kleffner syndrome and the syndrome of epilepsy with continuous spike wave during slow sleep, the spike index (SI) has been applied to quantify [Symbol: see text]interictal nocturnal focal epileptiform activity', which is suggested as a general term for the epileptiform activity enhanced by sleep. However, the SI has been implemented differently by different authors and has usually not been well described and never properly defined. This study suggests a definition of SI that gives a semiautomatic and relatively robust algorithm for assessment. The method employs spike detection by means of template matching of the current source density estimate. The percentage of time within an epoch with interspike interval (ISI) below a given limit, usually 3 s, is returned as the SI. This is calculated during daytime and in non-REM sleep. The standard epoch length is 10 min. The parameter selection is discussed in the context of the influence of spikes and bursts on cognition. The described method gives reproducible results in routine use, gives clinical valuable information, and is easily implemented in a clinical setting. There is only a minor added workload for the electroencephalographer.

KCNQ2 and KCNQ3 mutations contribute to different idiopathic epilepsy syndromes.

OBJECTIVE: To explore the involvement of M-type potassium channels KCNQ2, Q3, and Q5 in the pathogenesis of common idiopathic epilepsies. METHODS: Sequence analysis of the KCNQ2, Q3, and Q5 coding regions was performed in a screening sample consisting of 58 nuclear families with rolandic epilepsy. Subsequently, an association study was conducted for all discovered variants in a case-control sample comprising 459 German patients with idiopathic generalized epilepsy (IGE) and 462 population controls. RESULTS: An in-frame deletion of codon 116 in KCNQ2 (p.Lys116del) and a missense mutation in KCNQ3 (p.Glu299Lys) were detected in two index cases exhibiting rolandic epilepsy and benign neonatal convulsions. Both mutations resulted in reduced potassium current amplitude in Xenopus oocytes. Mutation analysis of families with rolandic epilepsy without neonatal seizures discovered three novel missense variations (KCNQ2 p.Ile592Met, KCNQ3 p.Ala381Val, KCNQ3 p.Pro574Ser). The KCNQ2 p.Ile592Met variant displayed a significant reduction of potassium current amplitude in Xenopus oocytes and was present only once in 552 controls. Both missense variants identified in KCNQ3 (p.Ala381Val and p.Pro574Ser) were present in all affected family members and did not occur in controls, but did not show obvious functional abnormalities. The KCNQ3 missense variant p.Pro574Ser was also detected in 8 of 455 IGE patients but not in 454 controls (p = 0.008). In KCNQ2, a silent single nucleotide polymorphism (rs1801545) was found overrepresented in both epilepsy samples (IGE, p = 0.004). CONCLUSION: Sequence variations of the KCNQ2 and KCNQ3 genes may contribute to the etiology of common idiopathic epilepsy syndromes.

Paroxysmal extreme pain disorder (previously familial rectal pain syndrome).

OBJECTIVE: To describe the clinical phenotype of paroxysmal extreme pain disorder (previously called familial rectal pain syndrome), an autosomal dominant condition recently shown to be a sodium channelopathy involving SCN9A. METHODS: An international consortium of clinicians, scientists, and affected families was formed. Clinical details of all accessible families worldwide were collected, including age at onset, features of attacks, problems between attacks, investigational results, treatments tried, and evolution over time. A validated pain questionnaire was completed by 14 affected individuals. RESULTS: Seventy-seven individuals from 15 families were identified. The onset of the disorder is in the neonatal period or infancy and persists throughout life. Autonomic manifestations predominate initially, with skin flushing in all and harlequin color change and tonic attacks in most. Dramatic syncopes with bradycardia and sometimes asystole are common. Later, the disorder is characterized by attacks of excruciating deep burning pain often in the rectal, ocular, or jaw areas, but also diffuse. Attacks are triggered by factors such as defecation, cold wind, eating, and emotion. Carbamazepine is effective in almost all who try it, but the response is often incomplete. CONCLUSIONS: Paroxysmal extreme pain disorder is a highly distinctive sodium channelopathy with incompletely carbamazepine-sensitive bouts of pain and sympathetic nervous system dysfunction. It is most likely to be misdiagnosed as epilepsy and, particularly in infancy, as hyperekplexia and reflex anoxic seizures.

A 3-year follow-up of headache diagnoses and symptoms in Swedish schoolchildren.

Information is sparse concerning the incidence and prognosis of headache in children from the general population, especially of tension-type headache. In this study, headache diagnoses and symptoms were reassessed in 122 out of 130 schoolchildren after 3 years. Nearly 80% of those with headache at first evaluation still reported headache at follow-up. Although the likelihood of experiencing the same headache diagnosis and symptoms was high, about one-fifth of children with tension-type headache developed migraine and vice versa. Female gender predicted migraine and frequent headache episodes predicted overall headache at follow-up. The estimated average annual incidence was 81 and 65 per 1000 children, for tension-type headache and migraine, respectively. We conclude that there is a considerable risk of developing and maintaining headache during childhood. Headache diagnoses should be reassessed regularly and treatment adjusted. Girls and children with frequent headache have a poorer prognosis and therefore intervention is particularly important in these groups.

Prevalence of headache in Swedish schoolchildren, with a focus on tension-type headache.

To estimate the prevalence of tension-type headache, migraine and other headaches, 1850 schoolchildren, age 7-15 years, from the city of Uppsala, were invited to complete a questionnaire. The response rate was 74.1%. To validate the information from the questionnaires, 131 children and their parents were interviewed. Using the criteria of the International Headache Society, the 1-year prevalence of tension-type headache and migraine was 9.8 and 11.0%, respectively. However, these prevalence rates increased considerably, to 23.0 and 17.0%, respectively, when excluding the criteria defining the number of earlier episodes and duration of headache. The prevalence of headache increased with age, similarly in girls and boys up to 11 years, and thereafter only in girls. The preponderance in teenage girls was even more pronounced for tension-type headache than for migraine. Our results indicate an increase over time in headache prevalence when compared with findings in a study conducted in the same city in 1955.

Herpesviral DNA in brain tissue from patients with temporal lobe epilepsy.

OBJECTIVES: Presence of DNA from six herpesviruses were examined in brain tissue from patients operated for temporal lobe epilepsy. MATERIAL AND METHODS: A total of 19 Canadian patients (I) with a median age of 22 years, 17 Swedish patients (II) with a median age of 14 years and a reference group comprising 12 individuals were studied. Presence of herpesviral DNA was detected by nested polymerase chain reaction. RESULTS: Of three children with Rasmussen's encephalitis, Cytomegalovirus (CMV) DNA was found in two, and human herpesvirus type 6 DNA in two. In six children with ganglioglioma, Epstein-Barr virus (EBV) was detected in four. CMV DNA was found significantly more in group I compared with II, while the reverse occurred with EBV DNA. Malformations of cortical development were found significantly more in group II compared with I. CONCLUSION: Detection of DNA from some herpesviruses in epileptic brain tissue may possibly be associated with distinct clinical conditions, but factors such as age and malformations of cortical development should also be considered.

Headache in schoolchildren: agreement between different sources of information.

The level of agreement between different sources of information, i.e. questionnaires, interviews and diaries, was evaluated in a sample of 129 schoolchildren, 69 girls and 60 boys, ranging in age from 7 to 17 years. Headache diagnoses and headache features showed high agreement between questionnaires and subsequent interviews. The concordance between questionnaires and interviews for headache diagnoses increased, and the number of unclassified headaches decreased, when the International Headache Society (IHS) duration criterion was excluded. When comparing headache frequency reported in questionnaires and interviews with diary recordings, the agreement was low and the frequency higher in the diaries. Overall, the agreement between questionnaires, interviews and diaries was not related to age or gender. The questionnaire may serve as a valid source of information in studies of headache in schoolchildren. Prospective recordings in diaries provide additional information, in particular of low-intensity headache. In children, the IHS duration criterion should be modified or excluded.

Non-neoplastic brain abnormalities on MRI in children and adolescents with neurofibromatosis type 1.

The occurrence, localization and longitudinal course of non-neoplastic MRI abnormalities in children and adolescents with neurofibromatosis type 1 (NF 1) were studied. Thirty-five patients who satisfied the criteria for NF 1 underwent 114 MRI examinations. They were 9 months to 18 years old at their first examination, and 23 were examined more than once (2 - 11 times). The follow-up time varied from 3 months to 10 years (mean 4 years). Thirty-one patients (89%) showed focal high signal intensities on T2-weighted images in the cerebellum, brain stem, deep cerebral gray matter and, less frequently, in the cerebral white matter. Changes were also seen in 80% and 50% of the proton density-weighted and T1-weighted images, respectively. Newly appearing, growing, decreasing and disappearing lesions occurred contemporaneously and in all ages. New lesions still developed in the late teens. Three lesions showed temporary contrast enhancement. Five expansive lesions were found in four individuals without related clinical symptoms. Four of them receded during follow-up. These cases indicate that the differential diagnosis between neoplastic and non-neoplastic lesions is not clear. The results support the view that high T2-signal lesions are so common in NF 1 that they should be included as another criterion for the diagnosis.

Atypical focal non-neoplastic brain changes in neurofibromatosis type 1: mass effect and contrast enhancement.

Children and young adults with neurofibromatosis type 1 often have small high-signal foci on T2-weighted images of the brain. We describe follow-up of two patients in whom one of the foci had atypical features, commonly regarded as signs of a neoplasm. In the first, one lesion showed temporary contrast enhancement and decreasing mass effect. The second developed an expanding lesion that increased minimally in size over 4.5 year's follow-up. The borderline between neoplastic and non-neoplastic lesions seems to be indistinct.

D-2-hydroxyglutaric aciduria with cerebral, vascular, and muscular abnormalities in a 14-year-old boy.

D-2-Hydroxyglutaric Aciduria is a rare metabolic disorder that can cause injury to the brain and other organs. This case report concerns a 14-year-old boy showing irritability and typical signs of pyloric stenosis early postnatally. From the age of 3 months he had epilepsy. He was mentally retarded, hypotonic with preserved reflexes, and dystonic. The features were dysmorphic with elongated head and high arched palate. Cardiomegaly with aortic insufficiency was diagnosed. Magnetic resonance imaging of the brain revealed atrophy, reduced periventricular white matter, and multiple bilateral aneurysms of the middle cerebral arteries. The boy died at the age of 14 years. Autopsy confirmed the white-matter reduction of the cerebral hemispheres as well as the arterial aneurysms of the middle cerebral arteries. Lesions of a few leptomeningeal and cerebral microvessels and of the renal and pulmonary arteries were also found. There were bilateral infarcts of the kidneys and signs of cardiomyopathy with noncompensated left ventricular failure. Signs of myopathy were evident. The clinical and postmortem findings imply a disseminated mesenchymal process.

MRI in rolandic epilepsy.

Hippocampal and/or white matter abnormalities have been found on the MRIs in 10/18 children with typical rolandic epilepsy. The etiology of the first-mentioned is not evident, whereas the latter may be a result of a maturational delay involving a defective myelination. Both abnormalities may cause cognitive dysfunction. In order to get a better understanding of rolandic epilepsy both MRI and neuropsychological studies are wanted in groups of children with typical rolandic seizures with and without rolandic sharp waves, as well as in groups of children with typical rolandic sharp waves and atypical seizures.

Hippocampal asymmetries and white matter abnormalities on MRI in benign childhood epilepsy with centrotemporal spikes.

PURPOSE: To look for brain abnormalities by using magnetic resonance imaging (MRI) in patients with benign childhood epilepsy with centrotemporal spikes (BCECTS), which is the most common epilepsy syndrome in children. METHODS: Eighteen children, aged 6-12 years, with typical BCECTS were examined with MRI, six of them twice. RESULTS: Some hippocampal abnormality was found in six (33%) of the children, all with the syndrome's typical electroencephalogram (EEG) pattern ipsilaterally. Hippocampal size asymmetry was found in five (28%) children (right side < left in two and left < right in three), and high signal intensities on T2-weighted images were found in three (17%). Two children also had other abnormalities; one had a heterotopic nodule near the contralateral frontal horn, and one had an Arnold-Chiari malformation. The hippocampal asymmetry remained unchanged in three of the children who were reexamined after 2 years. High signal intensities on T2-weighted images were seen beneath the cortex-white matter junction in the frontal and temporal lobes of five (28%) children, one of whom also had a hippocampal asymmetry. MRIs were normal in eight (44%) children. CONCLUSION: For the first time, hippocampal asymmetries and white-matter abnormalities have been detectable on the MRIs of children with typical BCECTS. The etiology of the former is unclear, whereas the latter may be a result of a maturational delay involving a defective myelination. Long-term follow-up studies are needed to evaluate the relation between these findings and the clinical course of BCECTS.

Medical technology assessment photic stimulation--standardization of screening methods.

RATIONALE: In many EEG laboratories in Europe, intermittent photic stimulation (IPS) is not performed routinely, and consequently, great variation exists in the type of photo stimulator used, the methodology employed, and the interpretation of the EEG curves, thus leading to different outcomes. METHODOLOGY: It was decided to hold a consensus meeting with experts in the field of photic stimulation from various European countries. This meeting was held at the Stichting Epilepsie Instellingen Nederland, Heemstede, the Netherlands. The consensus reached was presented and discussed at the 9th European Congress of Clinical Neurophysiology in Ljubjana in June 1998. RESULTS: Patients should be positioned at a distance of 30 cm from the photic stimulator (nasion to lamp) with dim surrounding lights, just enough to see the patient. Flashes should be delivered in separate trains of 10 s for each frequency, with intervals of 7 s minimum. First stimulation occurs with eyes open followed after 5 s by eye closure, while starting at 1 Hz progressing to 20 Hz, unless generalised epileptiform discharges are evoked at a lower frequency. Then, frequencies should start at 60 Hz decreasing to 25 Hz. The following frequencies should be used: 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 60, 50, 40, 30 and 25 Hz. The total duration is a maximum of 6 min (patients without a reaction to IPS). In interpreting the evoked responses, a clear distinction should be made between epileptiform responses confined to the occipital area (OSW), starting occipitally and spreading to frontal regions (OGSW), or generalised from the start (GSW). Other responses include generalised spikes (OR). CONCLUSION: This standard is safe, relatively quick, simple and reliable. Comparison of data within patients and between patients of various laboratories will also be possible. This will improve the quality of the care of the individual patient and make collaborative research possible.

D-2-hydroxyglutaric aciduria: further clinical delineation.

It has recently been recognized that D-2-hydroxyglutaric aciduria is a distinct neurometabolic disorder with a severe and a mild phenotype. Whereas the clinical and neuroimaging findings of the severe phenotype were homogeneous among the patients, the findings in the mild phenotype were much more variable, leaving the clinical picture poorly defined. We were able to collect the clinical, biochemical and neuroimaging data on an additional 8 patients with D-2-hydroxyglutaric aciduria, 4 with the severe and 4 with the mild phenotype. With the new information, it becomes clear that the mild phenotype shares the essential characteristics of the severe phenotype. The most frequent findings, regardless of the clinical phenotype, are epilepsy, hypotonia and psychomotor retardation. Additional findings, mainly occurring in the severe phenotype, are episodic vomiting, cardiomyopathy, inspiratory stridor and apnoeas. The most consistent MRI finding is enlargement of the lateral ventricles, occipital more than frontal. Regardless of the clinical phenotype, early MRI shows in addition subependymal cysts and signs of delayed cerebral maturation. Later MRI may reveal multifocal cerebral white-matter abnormalities. Two patients had vascular abnormalities, but it is as yet unclear whether these are related to D-2-hydroxyglutaric aciduria or are incidental findings.

Neuropsychological findings in children with benign childhood epilepsy with centrotemporal spikes.

Benign childhood epilepsy with centrotemporal spikes (BCECTS) is a well-known idiopathic age- and localization-related epileptic syndrome with characteristic clinical and EEG manifestations. Due to the reported benign evolution of this epilepsy syndrome, neuropsychological assessment has been considered unnecessary. However, the benign nature of BCECTS has recently been challenged: verbal dysfunction as well as impaired visuomotor coordination, specific learning disabilities, and attention deficit have been noticed. These findings prompted this research study in which all children with BCECTS attending our epilepsy clinic underwent neuropsychological assessment. Seventeen children (10 boys and seven girls) aged 7 to 14 years were investigated with a neuropsychological test battery focusing on immediate and delayed recall of auditory-verbal and visual material, verbal fluency, problem-solving ability, and visuospatial constructional ability. Raven's coloured matrices and questionnaires regarding school functioning and behaviour were also administered. The children were matched with control subjects for age, sex, and school. Children with BCECTS had significantly lower scores than their control subject partners on the neuropsychological items. Intellectual abilities did not differ and neither did school functioning or behaviour according to teachers. Parents, however, recognized greater difficulties with concentration, temperament, and impulsiveness in children with BCECTS.

Centrotemporal spikes in families with rolandic epilepsy: linkage to chromosome 15q14.

OBJECTIVE: To localize a gene predisposing to benign epilepsy of childhood with centrotemporal spikes (BECTS). BACKGROUND: BECTS, or rolandic epilepsy, is the most prevalent idiopathic epilepsy syndrome in childhood. Functional relevant defects in the alpha 4 subunit of the neuronal nicotinic acetylcholine receptor (AChR) have been demonstrated in autosomal dominant nocturnal frontal lobe epilepsy, which, like BECTS, is an idiopathic partial epilepsy. METHODS: A DNA linkage study was conducted screening all chromosomal regions known to harbor neuronal nicotinic AChR subunit genes. Twenty-two nuclear families with BECTS were analyzed. RESULTS: In an "affected-only" study, best p values and lod scores were reached between D15S165 and D15S1010 on chromosome 15q14. In multipoint nonparametric linkage analysis a nominal p value of 0.000494 was calculated by GENEHUNTER. Best parametric results were obtained under an autosomal recessive model with heterogeneity (multipoint lod score 3.56 with 70% of families linked to the locus). These markers are localized in direct vicinity to the alpha 7 subunit gene of the AChR. CONCLUSIONS: We found evidence for linkage of BECTS to a region on chromosome 15q14. Either the alpha 7 AChR subunit gene or a closely linked gene are implicated in pedigrees with BECTS. The disorder is genetically heterogeneous. Surprisingly, the same chromosomal area has been reported to be linked to the phenotype in families with an auditory neurophysiologic deficit as well as in families with juvenile myoclonic epilepsy, another idiopathic but generalized epilepsy syndrome.

Autosomal dominant nocturnal frontal-lobe epilepsy: genetic heterogeneity and evidence for a second locus at 15q24.

Autosomal dominant nocturnal frontal-lobe epilepsy (ADNFLE) is a recently identified partial epilepsy in which two different mutations have been described in the alpha4 subunit of the neuronal nicotinic acetylcholine receptor (CHRNA4). An additional seven families are presented in which ADNFLE is unlinked to the CHRNA4 region on chromosome 20q13.2. Seven additional sporadic cases showed no evidence of defective CHRNA4. One of the families showed evidence of linkage to 15q24, close to the CHRNA3/CHRNA5/CHRNB4 cluster (maximum LOD score of 3.01 with D15S152). Recombination between ADNFLE and CHRNA4, linkage to 15q24 in one family, and exclusion from 15q24 and 20q13.2 in others demonstrate genetic heterogeneity with at least three different genes for ADNFLE. The CHRNA4 gene and the two known CHRNA4 mutations are responsible for only a minority of ADNFLE. Although the ADNFLE phenotype is clinically homogeneous, there appear to be a variety of molecular defects responsible for this disorder, which will provide a challenge to the understanding of the basic mechanism of epileptogenesis.

[Moyamoya disease. A rare case of stroke in children?]. / Sykdommen moyamoya. En sjelden årsak til hjerneslag hos barn?

Moyamoya disease is a rare cerebrovascular disease with a wide variety of clinical outcomes. The main signs of the disease are progressive occlusion of the main intracerebral arteries and development of a special network of collateral vessels, Symptomatology can be intermittent, with light neurologic symptoms, or the disease can progress step-wise, with eventual physical and mental deterioration. Several operative methods have been evolved to improve cerebral bloodflow in this disease. We describe three children with Moyamoya disease. Two of them were the first patients offered operation for their disease in Norway. The article describes diagnostic measures, possible pathogenic mechanisms, and treatment.