Handgrip and finger flexion strength in children: A cross-sectional assessment of age-related normative data and application as a clinical functional marker in paediatric neuromuscular disorders.

BACKGROUND: The aim of this study was to evaluate handgrip and finger flexion strength (HGFS) as functional marker for disease progression in children with neuromuscular disorders (NMD) and present normative data in a paediatric healthy cohort. METHODS: We applied the fixed hand and finger dynamometer HFD 200 to assess HGFS under standardised, isometric and biomechanical conditions. In our cross-sectional study HGFS was analysed in n = 233 paediatric healthy controls (HC) and a cohort of n = 33 children with NMD between five and 18 years. In seven children with spinal muscular atrophy (SMA), HGFS were assessed prior to and under treatment with nusinersen over a two months period. HGFS of children with NMD was correlated with respiratory parameters, anthropometric data, hand function and motor scores. RESULTS: Patients with NMD exhibited a heterogenous HGFS pattern. HGFS was lower than in HC (p < 0.001). Children with SMA gained a significant increase in strength after two months of treatment (p < 0.05, r = 0.75-0.9). CONCLUSION: HGFS is a sensitive functional marker in paediatric NMD to identify minimal changes in distal muscle strength. HGFS may evolve as a sensitive outcome measure to monitor upcoming therapeutic interventions in particular for non-ambulant patients with NMD.

Acquired sensorimotor polyneuropathy in an adolescent boy with primary intracranial sarcoma.

Acquired polyneuropathies (PN) are rare in childhood and adolescent. We report on a 15-year-old male patient who presented with progressive gait instability, ataxia, neuropathic pain, distal muscle weakness and progressive loss of ambulation. Nerve conduction studies (NCS) revealed a progressive demyelinating sensorimotor polyneuropathy predominantly of the lower limbs. Cerebrospinal fluid (CSF) analyses revealed a cytoalbuminologic dissociation. Extensive diagnostic workup for autoantibodies and inflammatory markers was inconclusive. Corticosteroids and intravenous immunoglobulins did not affect. Cranial MRI revealed leptomeningeal enhancement of the cerebellum and the brainstem. Brain biopsy of the cerebellar lesions revealed an unclassifiable sarcoma. The patient was treated according to the CWS guidance study resulting in a decrease in enhanced lesion size. After two years NCS still revealed a demyelinating sensorimotor PN. This case report describes for the first time the clinical course of a chronic PN, putative paraneoplastic, associated with isolated unclassifiable CNS-sarcoma in an adolescent patient. Paraneoplastic pathogenesis should be considered in an unusual sequence of subacute progressive neurological symptoms even in children and adolescents.

[Evaluation of haemostasis in children treated with valproic acid]. / Untersuchungen zur Hämostase bei Kindern unter Valproatbehandlung.

UNLABELLED: Coagulation parameters were determined in children with valproic acid mono- and valproic acid-lamotrigin combination therapy. PATIENTS, METHODS: Monotherapy group (n = 22; mean age: 10.5 years) was compared to combination therapy (n = 7; 12.9 years) and a control group (n = 22; 8.7 years). The following parameters were measured: aggregation and ATP-release in whole blood (ADP: 20 µmol/l, collagen: 1 µg/ml, thrombin: 0.5 U/ml), PFA-100® closure times (CT), blood cell counts, global tests, VWF:Ag, VWF:CBA, factors VIII and XIII as well as fibrinogen. Bleeding symptoms were evaluated by using a questionnaire. RESULTS: For ADP- and collagen-induced aggregation as well as for ATP release no significant differences between the groups were detected. The combined therapy group showed significantly prolonged CT. Von Willebrand disease was not detected in any of the patients. The platelet count was significantly decreased in the monotherapy group. In six children a mild bleeding tendency was observed, mostly epistaxis. CONCLUSION: A clinically relevant influence of valproic acid on haemostasis was found only in few cases. However, before surgical procedures an extended coagulation diagnostics is recommended in patients with valproic acid therapy.

Facing the genetic heterogeneity in neuromuscular disorders: linkage analysis as an economic diagnostic approach towards the molecular diagnosis.

The identification of an ever increasing number of gene defects in patients with neuromuscular disorders has disclosed both marked phenotype and genotype variability and considerable disease overlap. In order to offer an economic strategy to characterise the molecular defect in patients with unclassified neuromuscular disorders, we designed DNA marker sets for linkage analysis of 62 distinct neuromuscular disorders gene loci, including all known muscular dystrophies, congenital myopathies, congenital myasthenic syndromes and myotonias. Genotyping of marker loci of 140 clinically well-characterised families with unclassified neuromuscular disorders reduced the number of candidates to one or two genes in 49 % of the families. Subsequent mutation analysis and genome-wide scans enabled the determination of the genetic defect in 31 % of the families including the identification of a new gene and a new mutation in an unexpected candidate gene. This highlights the effective application of this approach both for diagnostic strategies as well as for the identification of new loci and genes.