SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
A child with acute lymphoblastic leukaemia complicated by prolonged gastrointestinal and skin haemorrhages due to profound thrombocytopenia finally died of thrombotic occlusions of major cerebral arteries due to mucormycosis. Biopsy of any suspect lesion is needed urgently before prolonged therapy with amphotericin B is started. So far there have been no cures in childhood.
Explore the source record for details and available documents.
These 9 cases confirm that tuberose sclerosis, von Recklinghausen's neurofibromatosis, incontinentia pigmenti, linear warty sebaceous naevus and alopecic naevus resulting in a woolly naevus of the scalp may be complicated by flexion spasms with hypsarhythmia. Early diagnosis of hypsarhythmia makes possible specific treatment with ACTH or hydrocortisone.
Explore the source record for details and available documents.
PURPOSE: WWOX-related developmental and epileptic encephalopathy (WOREE) is a rare autosomal recessive disorder caused by biallelic pathogenic WWOX variants, characterized by very early-onset epilepsy, profound developmental delay, and progressive brain abnormalities. Detailed electroclinical descriptions remain limited. METHODS: We conducted a retrospective study of seven patients with pathogenic/likely pathogenic WWOX variants. Clinical features, seizure evolution, EEG findings, brain MRI, and genetic data were reviewed. Epilepsy syndromes were classified according to International League against Epilepsy (ILAE) criteria. Variants were identified through next-generation sequencing and interpreted following American College of Medical Genetics and Genomics (ACMG) guidelines. RESULTS: Median seizure onset was 3 months (range 2-6). Five patients presented with focal seizures evolving to infantile epileptic spasms syndrome (IESS), while two had IESS at onset. Epilepsy was drug-resistant in all. Developmental delay was evident from birth with generalized hypotonia, acquired microcephaly, and impaired visual attention. Four patients had dysmorphic features. During the IESS period, EEG showed hypsarrhythmia in six patients and a severely disorganized encephalopathic background that did not strictly fulfill the criteria for hypsarrhythmia in one. Brain MRI revealed abnormalities in all patients, including frontotemporal atrophy and corpus callosum hypoplasia; delayed myelination was observed in one case. Eight pathogenic/likely pathogenic WWOX variants were found; including one novel variant (NM_016373.4:c.571C>T, p.(Gln191*)). The recurrent splice-site variant NM_016373.4:c.107+1G>A was identified in five patients, suggesting a possible regional founder effect. CONCLUSION: WOREE shows a recognizable electroclinical and neuroimaging profile with early drug-resistant epilepsy and profound developmental delay. Recognition of this pattern may facilitate early diagnosis and targeted genetic testing, particularly in populations with recurrent variants.
A 7-month-old infant had the infantile spasm syndrome, consisting of flexor and extensor spasms, developmental delay, and hypsarrhythmia. Corticotropin produced delay, and hypsarrhythmia. Corticotropin produced improvement in the clinical symptoms and reverted the generalized electroencephalographic abnormalities to more focal ones. Removal of a choroid plexus papilloma of the left lateral ventricle was followed by clinical recovery. One year later the child was normal developmentally and neurologically and was seizure free on anticonvulsant therapy.
The electroencephalographic features and their evolutional changes with age were described in three cases of lissencephaly syndrome diagnosed by CT scan. The case with more severe lissencephaly displayed very similar EEG findings. In early or middle infancy when infantile spasms began, EEG showed very high amplitude (more than 400 microV) slow waves mixed with sharp theta-waves. In their clinical course, they showed extreme spindles and in late infancy, the EEG revealed a tendency towards bilaterally synchronous discharges of high amplitude sharp and slow waves. On the other hand, milder forms of lissencephaly showed hypsarrhythmia in early infancy. In the late infancy the EEG showed bisynchronous sharp and slow waves of more than 200 microV. The anomaly ranging from agyria to pachygyria seems to be closely associated with varying EEG abnormalities from extremely high voltage hypsarrhythmia to focal spikes. The very high voltage of hypsarrhythmic patterns and the very low frequency of sharp wave discharges seem to be typical in the most severe lissencephaly or agyria
This is the first description of a connatal case of adrenoleukodystrophy. The clinical picture consisted of severe psychomotor retardation, convulsions and hypsarrhythmia, but no obvious signs of adrenal insufficiency. Pathologically, the adrenals were small. The entire cortex was largely replaced by large round cells. Ultrastructurally, some cells in the adrenal cortex contained inclusions with electron-lucent clefts surrounded by a membrane. The anterior pituitary lobe could be demonstrated to have produced ACTH. The central nervous system showed extensive zones of demyelination in the brainstem, the cerebellum and the right-sided capsula interna. In the demyelinated areas there was sudanophilic breakdown and an intense gliosis. Ongoing demyelination could also be demonstrated by the chemical analysis. In the gray matter there waere micropolygyria of the insular cortex and swollen nerve cells in the nucleus arcuatus. Ultrastructure revealed the type of inclusions in the microglia of the same type as in the adrenals, and a different type of inclusions in unidentifiable cells, possibly neurons. These latter inclusions consisted of loosely stacked lamellar material. The findings are interpreted as further evidence of storage taking place in this disease.
BACKGROUND: Epilepsy of infancy with migrating focal seizures (EIMFS) is among the most severe developmental and epileptic encephalopathies (DEEs), marked by intractable multifocal seizures migrating across both hemispheres, profound developmental arrest, and high early mortality. Advances in next-generation sequencing have revealed a heterogeneous genetic architecture dominated by KCNT1 gain-of-function variants across more than 30 implicated genes, creating opportunities for precision therapeutics. OBJECTIVE: To systematically map published evidence on the clinical, electrophysiological, neuroimaging, genetic, and therapeutic landscape of EIMFS, and to delineate critical knowledge gaps and future research priorities. METHODS: A scoping review was conducted following the Arksey and O'Malley framework, searching PubMed, Ovid MEDLINE, Embase, Cochrane Library/CENTRAL, and ClinicalTrials.gov. RESULTS: Of 643 articles screened, 89 met inclusion criteria. Beyond confirmation of the canonical electroclinical phenotype, several gaps emerged: neonatal versus post-neonatal onset stratification by genetic etiology remains largely uncharacterized; genotype-specific EEG biomarkers are lacking except for a single small KCNT1 study; and the clinical significance of atypical EEG features-including burst suppression and hypsarrhythmia-is undefined. Neuroimaging literature documents progressive cerebral atrophy and myelination abnormalities without quantitative volumetry, diffusion tractography markers, or attribution to seizure burden, medication effects, or underlying etiology. Genetic diagnostic yield was 70-80%, with KCNT1 accounting for 30-50% of solved cases; however, genotype-outcome stratification is limited. Seizures were broadly refractory; potassium bromide, ketogenic diet, cannabidiol, and quinidine (in KCNT1-confirmed cases) showed partial efficacy. Emerging precision approaches include sodium channel blockers for SCN2A gain-of-function variants, novel small molecules, fluoxetine, antisense oligonucleotides, and divalent siRNA targeting KCNT1. Systemic-to-pulmonary collateral circulation causing severe cardiopulmonary complications was reported across multiple cases, yet no consensus screening protocol exists. CONCLUSIONS: EIMFS remains one of the most refractory epilepsy syndromes of infancy. Precision genetic diagnosis is essential to guide targeted therapy. International collaborative registries, standardized outcome measures, genotype-stratified biomarker studies, and rapid point-of-care genomic testing are urgently needed to advance evidence-based care for this highly vulnerable population.
Late-onset epileptic spasms (LOES) are epileptic spasms (ES) commencing after age 12 months, often misdiagnosed and having uncertain relationship to infantile spasms. Previous studies of mostly small LOES cohorts frequently reported 'cryptogenic' aetiologies. We studied the presentations, aetiologies, treatment responses and outcomes in a large LOES cohort, evaluated with modern neuroimaging and genomic testing. In this retrospective cohort study, 62 children with video-confirmed epileptic spasms, diagnosed between 2011 and 2021, were included. All had epileptiform activity on EEG, but none had hypsarrhythmia. Median age at epileptic spasms onset was 23 months (range 1-15 years) and median delay to diagnosis was 8 months (interquartile range: 3-15). Only 24% children were correctly diagnosed at presentation, common misdiagnoses being myoclonic epilepsies and non-epileptic phenomenon. Aetiology was identified in 95%. Structural-malformative aetiologies were present in 63% (most commonly focal cortical dysplasia and mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy). Other aetiologies were structural-acquired in 13% (mostly postnatal stroke and CNS infections), genetic in 13% (mostly intragenic variants and chromosomopathies) and oncological in 6% (history of leukaemia, two with CNS involvement). Children with structural aetiologies often had normal development prior to onset of epileptic spasms, a later median age of epileptic spasms onset and were more likely to have asymmetric or subtle epileptic spasms and additional seizures prior to epileptic spasms. Epileptic spasms ceased in 29% children treated with prednisolone, most having genetic aetiologies and in 35% treated with vigabatrin, all having structural-malformative aetiologies. Apart from clobazam, which was effective in 17% of children, all other antiseizure medications, vagus nerve stimulation and ketogenic diet therapy were ineffective. Epileptic spasms ceased in 86% (18/21) of children who underwent epilepsy surgery. At median follow-up of 10.3 years, 53% children were free of all seizures and 76% were free of epileptic spasms. More children with unilateral structural-malformative aetiologies achieved seizure freedom than other aetiologies, most commonly following surgery but occasionally following treatment with vigabatrin or clobazam. Impairment of cognitive function or adaptive behaviour (formally assessed in 90%) was significantly more common in children with genetic than structural aetiologies, and in children with ongoing seizures than seizure freedom. Among children who underwent epilepsy surgery, 62% achieved average or low-average adaptive functioning or normal intellectual capacity. This study highlights the importance of prompt recognition of epileptic spasms in older children for improved seizure and developmental outcomes. Brain malformations and insults are the predominant causes of LOES, and when unilateral, respond best to epilepsy surgery.
Myoclonus is a phenomenon which cuts through a considerable number of neurological conditions. It occurs in a variety of epileptic conditions (Primary generalized epilepsy, hypsarrhythmia, Lennox-Gastaut syndrome, also known as "petit mal variant"), in inborn errors of metabolism (Tay-Sachs disease, forms of ceroid lipofuscinosis), in neurobiochemically still poorly understood forms of degenerative processes such as Essential hereditary myoclonus epilepsy (Lafora-Unverricht-Lundborg), in benign heredo-degenerative disorders (Hartung's syndrome), in CNS infections (SSPE, Jakob-Creutzfeldt disease), in metabolic encephalopathies (renal failure, hypoglycemia), in CNS poisoning, in acute cerebral anoxia and in post-anoxic states. The EEG plays a crucial role in the differential diagnosis of these conditions by the demonstration of a) presence or absence of typical inter-ictal abnormalities, and b) various correlates of the myoclonic ictal event.
Clinical features were studied in 83 patients with slow spike-wave activity in the EEG. Epileptic seizures, usually intractable, occurred in 82 patients. The majority had the onset of seizures during the first 2 years of life. Minor motor seizures alone or in combination with other types of seizures occurred in 80 percent, and most had more than one type of seizure. The combination of tonic-clonic, minor motor, and absence seizures was the commonest, occurring in 37 percent. Sixty-six patients were definitely retarded and 49 showed definite motor impairment. Etiologic factors responsible for cerebral insult were identified in 53 patients. Serial EEG studies showed a close relationship between the EEG patterns of hypsarrhythmia, independent multifocal spike discharges, and slow spike-wave activity. The eponym "Lennox-Gastaut" syndrome is appropriate for a patient who has slow spike-wave activity in the EEG, exhibits mental retardation, and has intractable seizures of various types. However, the syndrome does not imply a pathologic entity because many diverse processes, both static and progressive, can produce this syndrome.
In a hypouricemic and mentally retarded infant due to a defect of 5-phosphoribosylpyrophosphate synthetase, electroencephalograms were recorded at the age of 4, 7, 10 and 11 months. Hypsarrhythmia was first observed at the age of 10 months, and markedly improved after ACTH therapy with concomitant increase in the enzyme activity of erythrocytes.
OBJECTIVE: To report the clinical manifestations, genetic features, diagnosis, treatment, and prognosis of a child with bilateral open-lip schizencephaly complicated by West syndrome due to a variant of PAFAH1B1 gene, and review the relevant literature. METHODS: Clinical data of a 4-month-old boy were retrospectively analyzed, and 35 previously reported cases were systematically reviewed. This study was approved by the Medical Ethics Committee of Gansu Provincial People's Hospital (Ethics No.: 2025-871). RESULTS: The 4-month-old boy presented with clustered flexor spasms, hypsarrhythmia on electroencephalography, and developmental regression. Brain magnetic resonance imaging revealed bilateral pachygyria, schizencephaly, and dysgenesis of the corpus callosum. Trio whole-exome sequencing identified a de novo heterozygous NM_000430.4: c.703_704delAG (p.Glu235Metfs*20) frameshift variant in the PAFAH1B1 gene. Sanger sequencing confirmed that neither parent carried this variant. Based on the guidelines from American College of Medical Genetics and Genomics (ACMG), the variant has met the criteria for PVS1+PS2_Moderate+PM2_Supporting, and was classified as pathogenic. After treatment with adrenocorticotropic hormone combined with vigabatrin and other antiseizure medications, the epileptic spasms were controlled and the electroencephalographic abnormalities had improved. However, global developmental delay persisted at the 12-month follow-up. Analysis of the present case and 35 previously reported cases showed that PAFAH1B1-related phenotypes were highly consistent, mainly including infantile spasms (28/36), developmental delay/intellectual disability (29/36), and abnormal brain MRI findings (30/36), predominantly cortical malformations. The reported variant types included deletions, frameshift variants, nonsense variants, missense variants, and splice-site variants. CONCLUSION: PAFAH1B1 gene variants are an important cause for cortical malformations, including schizencephaly, and may lead to secondary West syndrome. This study has systematically summarized the genotypic and phenotypic features of bilateral open-lip schizencephaly complicated by West syndrome associated with a frameshift variant of the PAFAH1B1 gene. For infants with epileptic spasms or early-onset epilepsy accompanied by structural brain abnormalities, early genetic evaluation should be performed, and antiseizure treatment should be integrated with neurodevelopmental rehabilitation to facilitate long-term management.
Looking for long-term prognostic value of the neonatal EEG, 545 records from 125 children in the pre-term and full-term period have been checked for special criterias: 1. Periods of electrocerebral inactivity (with usual amplifier gain) 2. Relative amplitude reduction over one of the hemispheres or localized 3. Focal changes 4. Epileptic activity: focal, multifocal and generalized. 5. Unspecific rhythm of alpha- and epsilon-frequency, which can not be classified as epileptic seizure pattern. According to the pronounciation of these criterias the EEG records were classified as severely, medium, severely, moderately abnormal and as normal. Comparison was done with the results of the last control EEG and the last clinical control examination. The principal results are: 1. Children with severe EEG abnormalities have a high mortality rate (about 70%). Long periods of electrocerebral inactivity are more unfavourable quoad vitam than epileptic discharges. 2. Late sequelae as cerebral palsy, psychomotor retardation and epilepsy are to be expected in all children with severe EEG abnormalities remaining alive and in many children with medium severe EEG abnormalities. 3. The rate of normal psychomotor development increases with the decrease of EEG abnormalities. It is important to mention: 1. EEG records in the first hours and days after birth give the best information regarding a long-term prognosis. 2. In children remaining alive and not developing hypsarrhythmia the observation interval must be more than one year for an estimation of probable electroencephalographic and clinical outcome.
Interrupting petit-mal status in infantile myoclonic seizures (n = 11), Lennox syndrom (n = 32), and in myoclonicastatic petit mal (n = 13) diazepame (Valium) and clonazepame (Rivotril) have been injected intraveneously in 56 patients during continuous EEG monitoring (38 patients with diazepame, 18 patients with clonazepame) (Table 1). A judgement according to the EEG findings and the apparent vigilance was performed thirty minutes after the injection was completed (Fig. 1 und 2; Table 3). Following results are presented: 1) There are no significant differences between clonazepame and diazepame with respect to therapeutic success (Table 3). 2. There are almost no differences concerning therapeutic success in the three forms of petit-mal status listed above (Table 3). 3) The initial success was 57%: 46% in infantile myoclonic seizures, 56% in Lennox syndrome, 70% in myoclonic-astatic petit-mal. The number of relapses for all forms was high: On the day following the injection only 18% of all patients did not show continued petit-mal-status: 18% in infantile myoclonic seizures, 15% in Lennox syndrome, 23% in myoclonicastatic petit mal (Table 3). 4) 13 patients were no longer in a status on the following day. 3 children were out of status spontaneously, independent from the intravenous application, 4 patients, one with infantile myoclonic seizures and 3 with Lennox syndrome, showed a focal EEG, 6 patients, 2 with infantile myoclonic seizures, 3 with Lennox syndrome, 4 with myoclonic-astatic petit mal, were further demonstrating generalised paroxysms (Fig. 1 und 2). 5) In infantile myoclonic seizures and in the Lennox syndrome almost always a focal EEG could be seen that accompanied the decrease of generalised paroxysms (hypsarrhythmia or 2/sec slow wave and spike). This finding has not been seen in the myoclonic-astatic petit mal, another sign that the latter is of primary generalised, "centrencephal" origin in contrast to the first two forms of convulsive disorders (Fig. 1, 2).