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

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.

Development and reliability of a classification system for gross motor function in children with metachromatic leucodystrophy.

AIM: Motor deterioration is a key feature of late infantile and juvenile metachromatic leucodystrophy (MLD). Assessment of the disease course implies the need for a standardized description of motor decline. The aim of this study was to establish a classification system for gross motor function in MLD and to assess its interrater reliability. METHOD: The Gross Motor Function Classification in MLD (GMFC-MLD) was modelled analogous to the Gross Motor Function Classification System in cerebral palsy. Motor data from 59 individuals (27 male; 32 female) with MLD (21 late infantile; 38 juvenile) born between 1970 and 2007 were gathered from a nationwide survey and classified by six independent raters. Median age at onset was 17 months (range 9-27 mo) for the late infantile group and 74 months (35-168 mo) for the juvenile group. RESULTS: The GMFC-MLD consists of seven levels and is applicable from the age of 18 months. It represents all clinically relevant stages from normal (level 0) to loss of all gross motor function (level 6). The kappa coefficient was 0.90 for overall rater agreement. There were no significant differences between level-specific kappa coefficients. INTERPRETATION: The GMFC-MLD is a highly reliable, feasible tool for standardized assessment of gross motor function in MLD which can be used for the description of the natural course of the disease and for evaluation of therapeutic options such as stem cell transplantation and enzyme replacement, both of which are topics of current research.

Association of Age at Onset and First Symptoms With Disease Progression in Patients With Metachromatic Leukodystrophy.

OBJECTIVE: To compare disease progression between different onset forms of metachromatic leukodystrophy (MLD) and to investigate the influence of the type of first symptoms on the natural course and dynamic of disease progression. METHODS: Clinical, genetic, and biochemical parameters were analyzed within a nationwide study of patients with late-infantile (LI; onset age ≤2.5 years), early-juvenile (EJ; onset age 2.6 to <6 years), late-juvenile (LJ; onset age 6 to <16 years), and adult (onset age ≥16 years) forms of MLD. First symptoms were categorized as motor symptoms only, cognitive symptoms only, or both. Standardized clinical endpoints included loss of motor and language functions, as well as dysphagia/tube feeding. RESULTS: Ninety-seven patients with MLD were enrolled. Patients with LI (n = 35) and EJ (n = 18) MLD exhibited similarly rapid disease progression, all starting with motor symptoms (with or without additional cognitive symptoms). In LJ (n = 38) and adult-onset (n = 6) patients, the course of the disease was as rapid as in the early-onset forms, when motor symptoms were present at disease onset, while patients with only cognitive symptoms at disease onset exhibited significantly milder disease progression, independently of their age at onset. A certain genotype-phenotype correlation was observed. CONCLUSIONS: In addition to age at onset, the type of first symptoms predicts the rate of disease progression in MLD. These findings are important for counseling and therapy. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with MLD, age at onset and the type of first symptoms predict the rate of disease progression.

Early clinical course after hematopoietic stem cell transplantation in children with juvenile metachromatic leukodystrophy.

BACKGROUND: Long-term outcomes of hematopoietic stem cell transplantation (HSCT) in children with juvenile metachromatic leukodystrophy (MLD) have been investigated systematically, while short-term effects of HSCT on the course of the disease remain to be elucidated. RESULTS: In this study, the clinical course was evaluated over the first 24 months following HSCT, conducted at our center in 12 children with juvenile MLD (mean follow-up 6.75 years, range 3-13.5) and compared with 35 non-transplanted children with juvenile MLD. Motor function (GMFM-88 and GMFC-MLD), cognitive function (FSIQ), peripheral neuropathy (tibial nerve conduction velocity), and cerebral changes (MLD-MR severity score) were tested prospectively. Seven children remained neurologically stable over a long period, five exhibited rapid disease progression over the first 12 to 18 months after transplantation. In the latter, time from first gross motor symptoms to loss of independent walking was significantly shorter compared with non-transplanted patients at the same stage of disease (p < 0.02). Positive prognostic factors were good motor function (GMFM = 100%, GMFC-MLD = 0) and a low MR severity score (≤ 17) at the time of HSCT. CONCLUSIONS: Our results show that if disease progression occurs, this happens early on after HSCT and proceeds faster than in non-transplanted children with juvenile MLD, indicating that HSCT may trigger disease progression.