Epileptic phenotypes, electroclinical features and clinical characteristics in 17 children with anti-NMDAR encephalitis.

BACKGROUND: Anti-N-methyl d-aspartate receptor (NMDAR) encephalitis is a rare disorder characterized by seizures, neuropsychiatric symptoms, dyskinesia and autonomic instability. OBJECTIVE: Aim of the present study was to evaluate the seizure phenotypes and electroencephalogram (EEG) features in children with anti-NMDAR encephalitis. METHODS: Seizure types, electroclinical features and clinical characteristics of 17 children with anti-NMDAR encephalitis were analysed in a retrospective case series from nine centres in Europe. RESULTS: Nearly half (8/17) of the children presented with psychiatric symptoms, whereas in 4/17 patients seizures were the first symptom and in 5/17 both symptoms occurred at the same time. During the following course seizures were reported in 16/17 children. The first EEG detected generalized slowing in 11/17 patients, focal slowing in 3/17 and normal background activity in only 3/17 children. The extreme delta brush (EDB) pattern was detected in 9/17 (53%) patients. CONCLUSION: In addition to psychiatric symptoms, children with anti-NMDAR encephalitis often show generalized slowing in EEG with or without seizures at initial presentation. EDB is present in half of all children and is potentially a helpful tool for early detection of this immune-mediated disease.

ASPP2 deficiency causes features of 1q41q42 microdeletion syndrome.

Chromosomal abnormalities are implicated in a substantial number of human developmental syndromes, but for many such disorders little is known about the causative genes. The recently described 1q41q42 microdeletion syndrome is characterized by characteristic dysmorphic features, intellectual disability and brain morphological abnormalities, but the precise genetic basis for these abnormalities remains unknown. Here, our detailed analysis of the genetic abnormalities of 1q41q42 microdeletion cases identified TP53BP2, which encodes apoptosis-stimulating protein of p53 2 (ASPP2), as a candidate gene for brain abnormalities. Consistent with this, Trp53bp2-deficient mice show dilation of lateral ventricles resembling the phenotype of 1q41q42 microdeletion patients. Trp53bp2 deficiency causes 100% neonatal lethality in the C57BL/6 background associated with a high incidence of neural tube defects and a range of developmental abnormalities such as congenital heart defects, coloboma, microphthalmia, urogenital and craniofacial abnormalities. Interestingly, abnormalities show a high degree of overlap with 1q41q42 microdeletion-associated abnormalities. These findings identify TP53BP2 as a strong candidate causative gene for central nervous system (CNS) defects in 1q41q42 microdeletion syndrome, and open new avenues for investigation of the mechanisms underlying CNS abnormalities.

Limbic encephalitis in children and adolescents.

OBJECTIVE: Limbic encephalitis is rare in people <18 years of age and rarely given a formal diagnosis. DESIGN: Retrospective study on presentation and outcome of children and adolescents with the clinico-radiological syndrome of limbic encephalitis tested for specific neuronal autoantibodies (Abs) over 3.5 years. SETTING: Assessment, diagnosis, treatment and follow-up at 12 neuropaediatric and neurological departments in Europe, with Abs determined in Bonn, Germany and Oxford, UK. PATIENTS: Ten patients <18 years of age who presented with a disorder mainly affecting the limbic areas of <5 years' duration with MRI evidence of mediotemporal encephalitis (hyperintense T2/FLAIR signal, resolving over time). RESULTS: Median age at disease onset was 14 years (range 3-17). Eight patients had defined Abs: one each with Hu or Ma1/2 Abs, four with high titre glutamic acid decarboxylase (GAD) Abs, two of whom had low voltage-gated potassium channel (VGKC) Abs and two with only low titre VGKC Abs. A tumour was only found in the patient with Hu Abs (a neuroblastoma). After a median follow-up of 15 months with corticosteroid or intravenous immunoglobulin treatment, starting after a median of 4 months, two patients recovered, eight remained impaired and one died. CONCLUSIONS: Limbic encephalitis is a disease that can occur in childhood or adolescence with many of the hallmarks of the adult disorder, suggesting that both result from similar pathogenic processes. Since most of the cases were non-paraneoplastic, as now also recognised in adults, more systematic and aggressive immunotherapies should be evaluated in order to improve outcomes.

Hippocampal abnormalities in malformations of cortical development: MRI study.

OBJECTIVES: Hippocampal abnormalities may coexist with malformations of cortical development (MCD). This cross-sectional MRI study aimed at categorizing hippocampal abnormalities in a large group of MCD and comparing MCD patients with (group W) and without (group W/O) hippocampal abnormalities. METHODS: Hippocampal anatomy, rotation, size, internal structure, and MRI signal alterations were assessed visually by 3 independent raters in patients with MCD and epilepsy. Four types of hippocampal abnormalities were examined in 220 patients (116 women, mean age 31 +/- 16.6, range 2-76 years): partially infolded/hypoplastic hippocampus (HH), hippocampal sclerosis (HS), malrotated hippocampus (MH), and enlarged hippocampus (EH). The commonest MCD in the cohort were focal cortical dysplasia (27%), polymicrogyria (PMG) (21%), developmental tumors (15%), and periventricular nodular heterotopia (PNH) (14%). RESULTS: Hippocampal abnormalities were seen in 69/220 (31%) patients: HH in 34/69 (49%); HS in 18/69 (26%); MH in 15/69 (22%); and EH in 2/69 (3%). PNH (21/30 [70%]) and PMG (22/47 [47%]) were most commonly associated with hippocampal abnormalities. Compared to the W/O group, patients in the W group had a higher rate of learning disability (W 41/69 [59%] vs W/O 56/151 [37%]; p = 0.003) and delayed developmental milestones (W 36/69 [52%] vs W/O 53/151 [35%]; p = 0.025); groups did not differ otherwise with regard to clinical presentation. HH was associated with symptomatic generalized epilepsies (11/34 [32%]) and high rate of learning disability (27/34 [79%]), neurologic deficits (25/34 [73%]), and delayed developmental milestones (23/34 [68%]). CONCLUSIONS: About a third of patients with malformations of cortical development had hippocampal abnormalities. Patients with hypoplastic hippocampus had the most severe clinical phenotype.

Electroclinical and imaging findings in ulegyria and epilepsy: a study on 25 patients.

PURPOSE: Ulegyria refers to cerebral cortex scarring, which results from a perinatal ischaemic brain injury. It presents with a characteristic gyral pattern: small circumvolutions with atrophy at sulci bottom and spared apex. Ulegyria is frequently associated with epilepsy, cerebral palsy and mental disability. We analysed electroclinical and MRI features in patients with ulegyria and epilepsy. PATIENTS AND METHODS: We reviewed 25 patients (14 males/11 females) with ulegyria and epilepsy from the database (about 5000 patients with epilepsy) of our unit. Patients were examined clinically, underwent high resolution MRI, EEG recordings, positron emission tomography, single photon emission computed tomography and neuropsychological testing. Two patients with refractory seizures underwent epilepsy surgery. RESULTS: Mean age of patients was 34 years (5-66) at the reassessment time. The majority (16/25, 64%) had a history of perinatal asphyxia. 15 patients had delayed developmental milestones; 20 had learning disabilities and five patients were severely disabled. Mean age at seizure onset was 4.2 years (1-18). 17 patients (68%) had medically intractable epilepsy. 11 patients (44%) had occipital lobe seizures. The majority (n = 24, 96%) had parieto-occipital lesions on MRI. In 13 patients (52%), ulegyria was bilateral. 12 patients (48%) had hippocampal sclerosis. Two patients underwent epilepsy surgery with an excellent postoperative outcome (Engel class IA and IC). CONCLUSION: Patients with ulegyria often have a history of perinatal asphyxia and present with pharmacoresistant seizures. Their presurgical assessment is complicated because of frequent dual pathology (hippocampal sclerosis) and bilateral lesions.

[SIDS prevention program in Tyrol]. / Das SIDS-Vorsorgeprogramm Tirol.

In April 1994, an intervention campaign to reduce the incidence of sudden infant death syndrome (SIDS) was established in the Tyrol. The campaign was intended to increase knowledge concerning risk factors for SIDS in the general community and to improve individual care for infants at risk. In contrast to interventional programmes in other federal states of Austria (i.e. Vorarlberg, Styria), this programme did not utilise polysomnography for identifying infants at risk. A part of the intervention programme was the "Styrian risk questionnaire", a standardised questionnaire concerning risk factors for SIDS. Individual instructions for health care of children at risk (risk score > or = 7) were provided and, if necessary, subscription of home monitoring was performed at the out-patient department (SIDS out-patient service) of the Department of Paediatrics in Innsbruck and other paediatric departments throughout the Tyrol. The educational programme also included information concerning basic life support. Psychological support was offered to parents of SIDS infants. Risk factors for SIDS in the Tyrol before the campaign were assessed in a retrospective case-control study (time period 1984-1994; 99 SIDS infants, 136 controls). The risk of SIDS was markedly reduced when parents had detailed knowledge of the risk factors of SIDS (odds ratio (OR) 0.03; p < 0.001), which emphasises the importance of information and educational programmes. The incidence of SIDS declined after the beginning of the intervention campaign from 1.83/1000 live births (average incidence from 1984-1994) to 0.4/1000 live births and remained at this level thereafter. Post-neonatal mortality also declined from 3.9 to 1.3/1000 live births. The prevalence of the prone sleeping position declined immediately after the campaign (53.7% vs. 5.4%, p < 0.001), as did the frequency of maternal smoking during pregnancy (22.9% vs. 14.5%, p < 0.01). Breast feeding became more popular. In all, the low-cost intervention programme in the Tyrol proved to be highly efficient in reducing the risk of SIDS and in maintaining this effect for several years.