Early initiation of ambroxol treatment diminishes neurological manifestations of type 3 Gaucher disease: A long-term outcome of two siblings.

Gaucher disease type 3 (GD3) is a severely debilitating disorder characterized by multisystemic manifestations and neurodegeneration. Enzyme replacement therapy alleviates visceral signs and symptoms but has no effect on neurological features. Ambroxol has been suggested as an enzyme enhancement agent. Some studies have confirmed its effectiveness in preventing the progression of neurological manifestations of neuronopathic Gaucher disease. In this study, we report two GD3 siblings in whom ambroxol combined with enzyme replacement therapy was initiated at different stages of the disease. We demonstrate the enzyme enhancement effect of ambroxol on L444P/H225Q;D409H glucocerebrosidase activity through results of fibroblast studies and long-term clinical outcomes of the two patients. The sibling diagnosed at the age of four-and-a-half years with significant neurological involvement manifested relatively rapid improvement on ambroxol treatment, followed by stabilization of further course. The younger sibling, in whom the treatment was started at seven weeks, displayed attention deficit and low average cognitive functioning at the age of seven years, but did not manifest other neurological symptoms. The difference in neurological outcomes indicates that ambroxol delayed or even halted the evolution of neurological manifestations in the younger sibling. This observation suggests that early initiation of ambroxol treatment may arrest neurological involvement in some GD3 patients.

Prognostic value of cranial ultrasonography in comparison with magnetic resonance imaging in children with cerebral palsy: a population-based study.

The aim of this population-based study was to evaluate the characteristics of cerebral palsy (CP) in relation to the predominant pattern of the Magnetic Resonance Imaging Classification System (MRICS) that was analogously applied to the neonatal/early infant cranial ultrasound (CUS). The study included children born during the 2004-2007 period from the Croatian part (C28 RCP-HR) of the Surveillance of Cerebral Palsy in Europe (SCPE) CP register. Motor functions, accompanying impairments and brain MRI were evaluated in 227 children, 185 of which also had CUS. Concerning CP types, 56% of children had bilateral spastic, 34% unilateral spastic, 9% dyskinetic and 1% ataxic CP type. Gross Motor Function Classification System (GMFCS) revealed that 62.05% had mild (GMFCS I-III) and 37.85% had severe motor impairment (GMFCS IV-V). CUS showed white matter injury in 60%, gray matter injury in 12%, maldevelopments in 8%, miscellaneous changes in 14%, while 6% were normal; MRI showed significant agreement (κ=0.675, p<0.001). Neuroimaging findings of maldevelopments and predominant gray matter injury were associated with more severe CP, but 7% of children with CP had normal MRI. As we found very good agreement between CUS and MRI findings, CUS is recommended in children at an increased risk of CP if MRI is not available.

Neurologic parameters in the perinatal period in children with neurodevelopmental disorders.

UNLABELLED: Cerebral palsy (CP) is a term encompassing a group of nonprogressive, noncontagious conditions causing mild, moderate or severe disorders of neurodevelopment. OBJECTIVE: Objective of this study was to analyze the possible prenatal etiological factors for the emergence of neurodevelopmental disorders (NDs) and CP from the medical records of 100 children with neuromotor disabilities who were treated in Special Hospital for Children with Neuro-developmental and Movement Disorders, Goljak, Croatia. RESULTS: ND and CP were more often diagnosed in children with birth weight below 2500 g which was statistically proved at the level of significance reaching 0.05, although significant correlation was low for both parameters reaching 0.21. There are both statistically significant differences and the statistically significant correlation between the three gestational age categories within ND and CP. There were more children with the birth weight below 2500 g in the CP than in the ND group and the difference was statistically significant. In the CP group, there were more children with the lower gestational age than in the ND group, which was statistically highly significant. This difference, together with correlation is significant at the level of 0.01. CONCLUSION: Further studies on the etiology of NDs are needed, with particular focus on the intrauterine risk factors.