IMPDH2: a new gene associated with dominant juvenile-onset dystonia-tremor disorder.

The aetiology of dystonia disorders is complex, and next-generation sequencing has become a useful tool in elucidating the variable genetic background of these diseases. Here we report a deleterious heterozygous truncating variant in the inosine monophosphate dehydrogenase gene (IMPDH2) by whole-exome sequencing, co-segregating with a dominantly inherited dystonia-tremor disease in a large Finnish family. We show that the defect results in degradation of the gene product, causing IMPDH2 deficiency in patient cells. IMPDH2 is the first and rate-limiting enzyme in the de novo biosynthesis of guanine nucleotides, a dopamine synthetic pathway previously linked to childhood or adolescence-onset dystonia disorders. We report IMPDH2 as a new gene to the dystonia disease entity. The evidence underlines the important link between guanine metabolism, dopamine biosynthesis and dystonia.

Effects of intensive therapy using gait trainer or floor walking exercises early after stroke.

OBJECTIVE: To analyse the effects of gait therapy for patients after acute stroke in a randomized controlled trial. METHODS: Fifty-six patients with a mean of 8 days post-stroke participated in: (i) gait trainer exercise; (ii) walking training over ground; or (iii) conventional treatment. Patients in the gait trainer exercise and walking groups practiced gait for 15 sessions over 3 weeks and received additional physiotherapy. Functional Ambulatory Category and several secondary outcome measures assessing gait and mobility were administered before and after rehabilitation and at 6-month follow-up. Patients also evaluated their own effort. RESULTS: Walking ability improved more with intensive walk training compared with conventional treatment; median Functional Ambulatory Category was zero in all patients at the start of the study, but it was 3 in both walk-training groups and 0.5 in the conventional treatment group at the end of the therapy. Median Functional Ambulatory Category was 4 in both walk-training groups and 2.5 in conventional treatment group at 6-month follow-up. Mean accomplished walking distance was not different between the gait trainer exercise and over ground walking groups. Borg scale indicated more effort in over ground walking. Secondary outcomes also indicated improvements. CONCLUSION: Exercise therapy with walking training improved gait function irrespective of the method used, but the time and effort required to achieve the results favour the gait trainer exercise. Early intensive gait training resulted in better walking ability than did conventional treatment.