K Weigt-Usinger

Pediatric Herpes Simplex Virus Encephalitis A Retrospective Multicenter Experience

Knowledge on pediatric herpes simplex virus encephalitis is limited. Here we summarize 6 neonates and 32 children diagnosed by polymerase chain reaction (n = 37) or serological studies (n = 1), respectively. Diagnosis was difficult, as only 15 patients presented neurologic symptoms. Moreover, cerebrospinal fluid glucose, protein, and leukocytes were normal in 6 patients. Subsequently, all but 2 showed neurologic symptoms. Diffusion-weighted neuroimaging was the most sensitive early imaging method. Despite acyclovir treatment, 8 patients experienced early relapses, showing movement abnormalities, impaired vigilance, and seizures. Diffuse white matter changes, found in 3 of 5 relapse patients on neuroimaging, and a negative cerebrospinal fluid herpes simplex virus polymerase chain reaction suggested inflammatory processes. All relapse patients were again treated with acyclovir, and 3 responded to additional corticosteroid treatment. Whereas outcome after relapses was poor, overall outcome was good. No child died; 14 were asymptomatic at discharge, and neuroimaging remained normal in 7 of 30 patients studied.

Long Survival in Leigh Syndrome: New Cases and Review of Literature

Leigh syndrome (MIM 25600), also known as infantile subacute necrotizing encephalomyelopathy, is a neurodegenerative disorder with characteristic bilateral symmetric lesions in basal ganglia and subcortical brain regions. It is commonly associated with systemic cytochrome c oxidase (COX) deficiency and mutations in the SURF1 gene (MIM 185620), encoding a putative assembly or maintenance factor of COX. The clinical course is dominated by neurodevelopmental regression, brain stem, and basal ganglia involvement (e.g., dystonia, apnea) with death often occurring before the age of 10 years. Herein, we present three sisters carrying a previously reported homozygous SURF1 mutation (c.868_869insT) that is predicted to result in a truncated protein with loss of function. Our patients show heterogeneous clinical findings with different distribution patterns of metabolic lesions in brain magnetic resonance imaging (MRI) as well as a Chiari malformation with hydrocephalus in one patient. However, all three siblings show an unusual long survival (12 years and>16 years). COX activity was not detectable in one patient and strongly reduced in the other two. We discuss these findings with respect to a review of the literature. A total of 15 additional patients with survival>14 years have been reported so far. Overall, no clear genotype-phenotype correlations are detectable among these patients.

Impact of Hippotherapy on Gross Motor Function and Quality of Life in Children with Bilateral Cerebral Palsy: A Randomized Open-Label Crossover Study

Abstract This study investigated the effect of hippotherapy on gross motor function (Gross Motor Function Measure [GMFM]‐66, GMFM dimension E and D) and quality of life (Child Health Questionnaire [CHQ 28], KIDSCREEN‐27 parental versions) in children with bilateral spastic cerebral palsy. Seventy‐three children (age: 9.1 ± 3.3 years; male = 44; GMFCS levels II = 27; III = 17; IV = 29) were randomized to an early (n = 35) or late (n = 38) treatment group. Data from 66 probands were available for further analysis. Probands received hippotherapy once to twice weekly during a period of 16 to 20 weeks (mean: 17 treatments) in a crossover approach. Whereas no significant changes were found for total GMFM scores and quality of life parameters, a significant increase in GMFM dimension E was found. Children terminating the study early showed lower mean psychosocial quality of life scores than children who completed the whole study (CHQ‐28 “psychosocial dimension”; KIDSCREEN‐27 “mood and emotional dimension”). Our data are in line with previous reports and suggest that hippotherapy shows distinct therapeutic strengths with regard to promoting upright stand and gait in children with cerebral palsy. Children with higher psychosocial burden of disease may need special support to get access to and benefit from intensified physiotherapy programs.

CNS findings in congenital muscular dystrophy 1A (with laminin alpha-2-deficiency)

Congenital muscular dystrophy (MDC) is a group of rare hereditary myopathies with an early onset of progressive muscle weakness and dystrophic changes as evidenced by muscle biopsy. Some forms are associated with severe malformations of the brain. This study presented 2 pediatric patients with genetically diagnosed congenital muscular dystrophy 1A. The patients exhibited a typical combination of muscular hypotonia, joint contractures and elevated creatine kinase levels. Characteristic white matter lesions were not present in an early MRI scan of one patient, but could be detected at the age of 18 months. The second patient showed both severe white and grey matter abnormalities (pachy microgyria) in the MRI scan. In both cases, MRI findings did not correlate with the mental development of the patients.

Muscular hypotonia, joint contractures and elevated creatin kinase level as main symptoms for Congenital muscular dystrophy 1A (MDC 1A/congenital muscular dystrophy with laminin α 2 (merosin) deficiency)

Introduction: congenital muscular dystrophies (MDC) are hereditary myopathies characterized by congenital muscular hypotonia, delayed motor development and early onset of progressive muscle weakness. Dystrophic patterns are found in muscular biopsy. Some forms are associated with affections of the brain or eyes. Incidental rate is ca. 2.5–4.5×(10–5). The congenital muscular dystrophy with laminin α 2 -deficiency (MDC1A) counts ca. 30 to 40% of all MDC in Europe. A defect of laminin α 2 affects primarily the basement membrane of the muscular cell. Case report 1: We describe a girl with muscular hypotonia, delayed motor development, proximal muscular weakness, lacking of head control, joint conctractures and absence of muscular reflexes at the age of 10 weeks. Creatine kinase was markedly elevated (3510U/l). Echocardiography and electrocardiogram were normal. The MRI of brain was normal, muscle MRI showed substantial edematous changes. Active dystrophic patterns were found in muscular biopsy. Immunohistochemical analysis of laminin α-2 showed absence of expression. Analysis of the laminin α 2-gene on chromosome 6q2 could detect a homozygous mutation (Exon 36: IVS36+1G>A), which was heterozygous found at the consanguinous parents. Now 9 month old, the girls grows well, no significant motor development is seen, one respiratory infection due to RS-virus with need of oxygene supply. Case report 2: Second patient showed a postnatal muscular hypotonia without breathing oder feeding problems. At age of 5 months no significant motor development, proximal muscular weakness, joint contractures und no muscular reflexes. Elevation of creatine kinase was significant (2604U/l). Normal echocardiography an electrocardiogram. In the laminin α 2 -gene 2 different mutations Heterozygotie (Exon 32: c.4645C>T p,ARg1549X, Exon 4: c.498G>A p,Trp166X) were found, each of came from 1 parent, who were not consanguinous. Now 15 month old minimal progress in motoric function can be seen (turn from supine position to the side is possible, playing with toys in supine position), no problems concerning respiration and as far no delay in speech an cognitive development. In comparison to the presented girl seems the muscular fonction to be slightly better. Conclusion: We present 2 children with genetically diagnosed congenital muscular dystrophy 1A with typical combination of muscular hypotonia, joint contractures and elevates creatin kinase level.