Aicardi–Goutières syndrome is an inflammatory disease occurring due to mutations in any of TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR or IFIH1. We report on 374 patients from 299 families with mutations in these seven genes. Most patients conformed to one of two fairly stereotyped clinical profiles; either exhibiting an in utero disease-onset (74 patients; 22.8% of all patients where data were available), or a post-natal presentation, usually within the first year of life (223 patients; 68.6%), characterized by a sub-acute encephalopathy and a loss of previously acquired skills. Other clinically distinct phenotypes were also observed; particularly, bilateral striatal necrosis (13 patients; 3.6%) and non-syndromic spastic paraparesis (12 patients; 3.4%). We recorded 69 deaths (19.3% of patients with follow-up data). Of 285 patients for whom data were available, 210 (73.7%) were profoundly disabled, with no useful motor, speech and intellectual function. Chilblains, glaucoma, hypothyroidism, cardiomyopathy, intracerebral vasculitis, peripheral neuropathy, bowel inflammation and systemic lupus erythematosus were seen frequently enough to be confirmed as real associations with the Aicardi-Goutieres syndrome phenotype. We observed a robust relationship between mutations in all seven genes with increased type I interferon activity in cerebrospinal fluid and serum, and the increased expression of interferon-stimulated gene transcripts in peripheral blood. We recorded a positive correlation between the level of cerebrospinal fluid interferon activity assayed within one year of disease presentation and the degree of subsequent disability. Interferon-stimulated gene transcripts remained high in most patients, indicating an ongoing disease process. On the basis of substantial morbidity and mortality, our data highlight the urgent need to define coherent treatment strategies for the phenotypes associated with mutations in the Aicardi–Goutières syndrome-related genes. Our findings also make it clear that a window of therapeutic opportunity exists relevant to the majority of affected patients and indicate that the assessment of type I interferon activity might serve as a useful biomarker in future clinical trials.

Children with MDEM and persisting MOG antibodies constitute a distinct entity of relapsing demyelinating events and extend the spectrum of MOG antibody-associated diseases.

Objective: Food cues yield different patterns of brain activation in obese compared with normal-weight adults in prefrontal and limbic/paralimbic areas. For children, no mapping studies comparing representation sites for food and other stimuli between obese and normal-weight subjects are available. Design: We used a cross-sectional design of two age-matched subject groups to investigate differences in brain activation in response to visually presented food, pleasant, and neutral pictures between obese/overweight and normal children. Subjects: 22 overweight/obese children were compared with 22 normal-weight children. Measurements: Functional magnetic resonance imaging (of the whole head during perception of visually presented stimuli), psychological testing, and psychophysical measures of heart rate deceleration were assessed. Results: Obese children showed higher activation of the dorsolateral prefrontal cortex (DLPFC) in response to food pictures. In addition, DLPFC activation was negatively correlated with self-esteem. In contrast, normal-weight children showed higher activation of the caudate and hippocampus specific to food pictures, and of the anterior cingulate cortex and thalamus to visual cues in general. In response to food stimuli, obese children showed a heart rate deceleration correlating positively with activation of the ventrolateral prefrontal cortex. Conclusion: Obese children react to food stimuli with increased prefrontal activation, which might be associated with increased inhibitory control.

In this series of patients with SMA I through III who underwent sural nerve biopsy, there was significant sensory nerve pathology in severely affected patients with SMA type I, whereas there were no sensory nerve alterations clinically or morphologically in patients with milder SMA type II or III.

In order to extract and to visualize qualitative information from a high-dimensional time series, we apply ideas from symbolic dynamics. Counting certain ordinal patterns in the given series, we obtain a series of matrices whose entries are symbol frequencies. This matrix series is explored by simple methods from nominal statistics and information theory. The method is applied to detect and visualize qualitative changes of EEG data related to epileptic activity.

Familial hemiplegic migraine (FHM) and alternating hemiplegia of childhood (AHC) are severe neurological disorders that share clinical features. Therefore, FHM genes are candidates for AHC. We performed mutation analysis in the CACNA1A gene in a monozygotic twin pair with clinical features overlapping with both AHC and FHM and identified a novel de novo CACNA1A mutation. We provide the first evidence that a CACNA1A mutation can cause atypical AHC, indicating an overlap of molecular mechanisms causing AHC and FHM. These results also suggest that CACNA1A mutation scanning is indicated in patients with a severe neurological phenotype that includes paroxysmal (alternating) hemiplegia.

No abstract

BAEPs were recorded from 92 healthy children with a gestational age of 35 weeks up to 16 years. The maturation kinetic of I-III and I-V interpeak latency can well be approximated by the exponential regressions I-V : y = 0.9588 x e -0.9215 x x + 3.9728; r = 0.87; I-III : y = 0.6182 x e -1.1737 x x + 2.1759; r = 0.81; Adult values are reached by about two years of life. In contrast to this immaturity of the central auditory pathways the slopes of latency--intensity functions of waves I and V show no significant differences between premature infants and neonates versus older children over three years. Caused by the prolonged I-V IPL wave V latency is about 1 ms longer in the first group, whereas wave I is only slightly prolonged (0.2 ms) within the first three months of life.