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We retrospectively evaluated predictors of conversion to multiple sclerosis (MS) in 357 children with isolated optic neuritis (ON) as a first demyelinating event who had a median follow-up of 4.0 years. Multiple Cox proportional-hazards regressions revealed abnormal cranial magnet resonance imaging (cMRI; HR 5.94; 95% CI: 3.39-10.39; p

Introduction: Deep brain stimulation of the globus pallidus internus (GPi-DBS) can be effective in patients with dyskinetic cerebral palsy (CP), but outcome in terms of dystonia severity is often less pronounced and more variable compared to patients with inherited monogenic dystonia. A few published case series encompassing retrospective data have shown that GPi-DBS is associated with favorable quality of life outcomes, even in patients without changes in the BFMDRS, suggesting that the sole use of clinical rating scales may not reflect the full effects of DBS, especially not in patients with acquired forms of dystonia such as dyskinetic CP. However, there is no prospective data on DBS effects in children. We hypothesize an improvement in quality of life by GPi-DBS. Therefore, the mean change in the CPCHILD questionnaire from baseline to 12 months is chosen as the primary outcome parameter. Secondary outcome parameters encompass dystonia severity, motor function, speech, mood, cognition, pain, and quality of life of the carers before and up to 36 months after implantation. Methods: This is a prospective single-arm study to investigate the effects of GPi-DBS in young patients with dyskinetic CP. 20 patients aged 7-18 years will be recruited in a multicenter setting. 12 months after lead implantation patients are randomized by a double-blind cross-over into two groups: One group starts with ongoing stimulation, in the other group stimulation is turned off. After 24 h they switch stimulation settings. Dystonia severity will be assessed at the end of each phase. We hypothesize an improvement in quality of life by GPi-DBS. Therefore, the mean change in the CPCHILD questionnaire from baseline to 12 months is chosen as the primary outcome parameter. Secondary outcome parameters encompass dystonia severity, motor function, speech, mood, cognition, pain, and quality of life of the carers before and up to 36 months after implantation. Discussion: This is the first prospective trial investigating the effects of GPi-DBS on motor and non-motor outcome in a cohort of exclusively pediatric patients in a multicenter setting. Furthermore, long-term data on effects and side effects of GPi-DBS in young patients with dyskinetic cerebral palsy will be generated.

SUMMARY Data on prevalence, impairments, neuropaediatric and ophthalmologic findings are reported in a population-based study of 239 multihandicapped blind and partially sighted children in South Germany born between 1981 and 1987. With a prevalence of 0.67 per 1000 live births this type of impairment was rare. However, most children in this series were very severly impaired with very low developmental age and several additional impairments. Most children had lesions of the visual pathways without significant involvement of the eyes. Ophthalmological and neuroradiological findings indicated that optic nerve atrophy and lesions of the posterior visual pathways frequently coexisted. RESUME Enfants mitltihandicapes aveugles on malvoyants en Allemagnc du Sud. I: Prevalence, troubles et donnees ophtalmologiques L'article rapporte les donnees sur la prevalence, les troubles et les donnees neuropediatriques et ophtalmologiques dans une etude de population en Allemagnc du Sud de 239 enfants aveugles ou malvoyants multihandicapes nes entre 1981 et 1987. Bien que cette forme de handicap soit rare (prevalence de 0.67 pour 1000 naissances vivantes), la plupart des enfants atteints etaient gravement touches, ayant un âge de developpement tres bas et des troubles graves associes. La plupart avaient des lesions des voies visuelles sans effet direct sur l'oeil. Une atrophie du nerf optique et des lesions des voies visuelles posterieures coexistaient souvent. ZUSAMMENFASSUNG Mehifachbehinderte blinde itnd sehbehinderte Kinder in Suddeutschland. I: Haufigkeit, Behinderungen und opluhalmologische Befunde Von 239 mehrfachbehinderten blinden bzw. sehbehinderten Kindem, die zwischen 1981 und 1987 geboren wurden, werden die im Rahmen einer Bevolkerungsbezogenen Studie in Suddeutschland erhobenen Daten uber Haufigkeit, Behinderungen und neuropadiatrische und ophthalmologische Befunde beschrieben. Obwohl diese Form der Behinderung selten war (Haufigkeit 0.67 pro 1000 Lebendgeburten), waren die meisten betroffenen Kinder sehr schwer behindert, sie hatten ein niedriges Entwicklungsalter und mehrere zusatzliche Behinderungen. Die meisten hatten Lasionen der Sehbahnen ohne signifikante Auswirkungen auf die Augen. Sehnervenatrophie und Lasionen der hinteren Sehbahnen traten haufig gleichzeitig auf. RESUMEN Ninos con multiples deficiencias, ciegos y parcialmente videntes en el sur de Alemania. I: Prevalencia; alteracion. es y ballazgos oftalmologicos Se aportan los datos sobre prevalencia, alteraciones y hallazgos neuropediatricos y oftalmologicos en un estudio de poblacion en el sur de Alemania de 239 ninos con multiples deficiencias, ciegos o parcialmente videntes, nacidos entre 1981 y 1987. Aunque esta forma de deficiencia era rara (prevalencia 0.67 por 1000 nacidos vivos) la mayoria de los ninos afectados lo estaban gravemente con una edad de desarrollo muy baja y diversas alteraciones adicionales. La mayoria tenian lesiones de las vias visuales sin efecto significativo en los ojos. Con frecuencia coexistian atrofia del nervio optico y lesiones de las vias opticas posteriores.

Item does not contain fulltext Tyrosine hydroxylase (TH) is the key enzyme in the biosynthesis of the catecholamines dopamine, epinephrine, and norepinephrine. Recessively inherited deficiency of TH was recently identified and incorporated into recent concepts of genetic dystonias as the cause of recessive Dopa-responsive dystonia or Segawa's syndrome in analogy to dominantly inherited GTP cyclohydrolase I deficiency. We report four patients with TH deficiency and two with GTP cyclohydrolase I deficiency. Patients with TH deficiency suffer from progressive infantile encephalopathy dominated by motor retardation similar to a primary neuromuscular disorder, fluctuating extrapyramidal, and ocular and vegetative symptoms. Intellectual functions are mostly compromised. Prenatally disturbed brain development and postnatal growth failure were observed. Treatment with levodopa ameliorates but usually does not normalize symptoms. Compared with patients with dominantly inherited GTP cyclohydrolase I deficiency, catecholaminergic neurotransmission is severely and constantly impaired in TH deficiency. In most patients, this results not in predominating dystonia, a largely nondegenerative condition, but in a progressive often lethal neurometabolic disorder, which can be improved but not cured by L-dopa. Investigations of neurotransmitter defects by specific cerebrospinal fluid determinations should be included in the diagnostic evaluation of children with progressive infantile encephalopathy.

We retrospectively evaluated predictors of conversion to multiple sclerosis (MS) in 357 children with isolated optic neuritis (ON) as a first demyelinating event who had a median follow-up of 4.0 years. Multiple Cox proportional-hazards regressions revealed abnormal cranial magnet resonance imaging (cMRI; hazard ratio [HR] = 5.94, 95% confidence interval [CI] = 3.39-10.39, p 0.001), presence of cerebrospinal fluid immunoglobulin G oligoclonal bands (OCB; HR = 3.69, 95% CI = 2.32-5.86, p 0.001), and age (HR = 1.08 per year of age, 95% CI = 1.02-1.13, p = 0.003) as independent predictors of conversion, whereas sex and laterality (unilateral vs bilateral) had no influence. Combined cMRI and OCB positivity indicated a 26.84-fold higher HR for developing MS compared to double negativity (95% CI = 12.26-58.74, p 0.001). Accordingly, cerebrospinal fluid analysis may supplement cMRI to determine the risk of MS in children with isolated ON.

We report a branch site mutation in the gene of the enzyme tyrosine hydroxylase (TH): a −24t > a substitution two bases upstream of the adenosine in the branchpoint sequence (BPS) of intron 11. As normal lariat formation is therefore prevented, alternative splicing takes place: use of the BPS of intron 12 results in skipping of exon 12, whereas the use of a cryptic branch site in intron 11 leads to partial retention of this intron in the mRNA. This leads in both cases to an aberrant protein product. In the one case, skipping of exon 12 results in the absence of 32 amino acids. In the other, retention of 36 nucleotides of intron 11 in the mRNA results in the incorporation of twelve additional amino acids. The functional consequences of this mutation for the patient, who is also heterozygous for another previously identified mutation, become apparent in a severe clinical phenotype.

Marinesco-Sjogren syndrome is a rare autosomal recessive multisystem disorder featuring cerebellar ataxia, early-onset cataracts, chronic myopathy, variable intellectual disability and delayed motor development. More recently, mutations in the SIL1 gene, which encodes an endoplasmic reticulum resident co-chaperone, were identified as the main cause of Marinesco-Sjogren syndrome. Here we describe the results of SIL1 mutation analysis in 62 patients presenting with early-onset ataxia, cataracts and myopathy or combinations of at least two of these. We obtained a mutation detection rate of 60% (15/25) among patients with the characteristic Marinesco-Sjogren syndrome triad (ataxia, cataracts, myopathy) whereas the detection rate in the group of patients with more variable phenotypic presentation was below 3% (1/37). We report 16 unrelated families with a total of 19 different SIL1 mutations. Among these mutations are 15 previously unreported changes, including single- and multi-exon deletions. Based on data from our screening cohort and data compiled from the literature we found that SIL1 mutations are invariably associated with the combination of a cerebellar syndrome and chronic myopathy. Cataracts were observed in all patients beyond the age of 7 years, but might be missing in infants. Six patients with SIL1 mutations had no intellectual disability, extending the known wide range of cognitive capabilities in Marinesco-Sjogren syndrome to include normal intelligence. Modestly constant features were somatic growth retardation, skeletal abnormalities and pyramidal tract signs. Examination of mutant SIL1 expression in cultured patient lymphoblasts suggested that SIL1 mutations result in severely reduced SIL1 protein levels irrespective of the type and position of mutations. Our data broaden the SIL1 mutation spectrum and confirm that SIL1 is the major Marinesco-Sjogren syndrome gene. SIL1 patients usually present with the characteristic triad but cataracts might be missing in young children. As cognitive impairment is not obligatory, patients without intellectual disability but a Marinesco-Sjogren syndrome-compatible phenotype should receive SIL1 mutation analysis. Despite allelic heterogeneity and many families with private mutations, the phenotype related to SIL1 mutations is relatively homogenous. Based on SIL1 expression studies we speculate that this may arise from a uniform effect of different mutations on protein expression.