Basal Ganglia Atrophy as a Marker for Prodromal X-Linked Dystonia-Parkinsonism.

In neurodegenerative diseases, the characterization of the prodromal phase is essential for the future application of disease-modifying therapies. X-linked dystonia-parkinsonism is a hereditary neurodegenerative movement disorder characterized by severe adult-onset dystonia accompanied by parkinsonism. Distinct striatal and pallidal atrophy is present already in early disease stages indicating a long-lasting presymptomatic degenerative process. To gain insight into the prodromal phase of X-linked dystonia-parkinsonism, structural and iron-sensitive magnetic resonance imaging (MRI) was performed in 10 non-manifesting carriers and 24 healthy controls in a double-blind fashion. Seventeen patients with X-linked dystonia-parkinsonism were recruited to replicate previous findings of basal ganglia pathology and iron accumulation. Age at onset was estimated in non-manifesting carriers and patients using the repeat length of the hexanucleotide expansion and 3 single-nucleotide polymorphisms associated with age at onset. Voxel-based morphometry and subcortical volumetry showed striatal and pallidal atrophy in non-manifesting carriers (~10%) and patients (~40%). Substantia nigra volume was similarly reduced in patients (~40%). Caudate volume correlated with time to estimated onset in non-manifesting carriers. Susceptibility-weighted imaging confirmed iron deposition in the anteromedial putamen in patients. Non-manifesting carriers also showed small clusters of iron accumulation in the same area after lowering the statistical threshold. In conclusion, basal ganglia atrophy and iron accumulation precede the clinical onset of X-linked dystonia-parkinsonism and can be detected years before the estimated disease manifestation. It thereby highlights the potential of multimodal imaging to identify clinically unaffected mutation carriers with incipient neurodegeneration and to monitor disease progression independent of clinical measures. Longitudinal studies are needed to further elucidate the onset and progression rate of neurodegeneration in prodromal X-linked dystonia-parkinsonism. ANN NEUROL 2023;93:999-1011.

Both thalamic and pallidal deep brain stimulation for myoclonic dystonia.

Myoclonic dystonia is poorly managed with medication and may be severe enough to warrant surgical intervention. Surgery has targeted either the globus pallidus pars interna (GPi) or the thalamus, but there is no accepted target for this condition. The authors present the case of a 23-year-old man treated with unilateral deep brain stimulation in both the thalamus and GPi. His movement disorder improved dramatically with stimulation. Two years postoperatively, the authors performed a double-blind assessment of the effects of each stimulator together, separately, and off stimulation. Videotape assessment, using tremor, dystonia, and myoclonus rating scales, showed that most of the benefit could be attributed to pallidal stimulation, although there was some advantage to stimulation at both sites. These results suggest that while GPi stimulation may be the better target for this condition, thalamic stimulation may be added in cases in which the benefit is insufficient.