Paramedical treatment in primary dystonia: a systematic review

Dystonia is a disabling movement disorder with a significant impact on quality of life. The current therapeutic armamentarium includes various drugs, botulinum toxin injections, and occasionally (neuro)surgery. In addition, many patients are referred for paramedical (including allied health care) interventions. An enormous variation in the paramedical treatment is provided, largely because evidence-based, accepted treatment regimes are not available. We have conducted a systematic review of studies that explored the effect of various paramedical interventions in primary dystonia. Only studies that have used clinical outcome measures were included. There were no class A1 or A2 studies and therefore, level 1 or 2 practice recommendations for a specific intervention could not be deducted. Many papers were case reports, mostly with a very limited number of patients and a clear publication bias for beneficial effects of a particular paramedical intervention. Some potentially interesting interventions come from class B studies, which include physical therapy in addition to botulinum toxin injections (BoNT-A) in cervical dystonia; sensorimotor training and transcutaneous electrical nerve stimulation (TENS) in writer's cramp; and speech therapy added to BoNT-A injections in laryngeal dystonia. Good quality clinical studies are therefore warranted, which should have the aim to be generally applicable. A design in which the paramedical intervention is added to a current gold standard, for example, BoNT-A injections in cervical dystonia, is recommende

Origin of the mutations in the parkin gene in Europe: Exon rearrangements are independent recurrent events, whereas point mutations may result from founder effects

A wide variety of mutations in the parkin gene, including exon deletions and duplications, as well as point mutations, result in autosomal recessive early-onset parkinsonism. Interestingly, several of these anomalies were found repeatedly in unrelated patients and may therefore result from recurrent, de novo mutational events or from founder effects. In the present study, haplotype analysis, using 10 microsatellite markers covering a 4.7-cM region known to contain the parkin gene, was performed in 48 families, mostly from European countries, with early-onset autosomal recessive parkinsonism. The patients carried 14 distinct mutations in the parkin gene, and each mutation was detected in more than one family. Our results support the hypothesis that exon rearrangements occurred independently, whereas some point mutations, found in families from different geographic origins, may have been transmitted by a common founder

Gender differences in Parkinson's disease

Contains fulltext : 53439.pdf (publisher's version ) (Closed access)OBJECTIVE: To investigate gender differences in basic disease characteristics, motor deterioration and nigrostriatal degeneration in Parkinson's disease (PD). METHODS: We studied 253 consecutive PD patients who were not receiving levodopa or dopamine agonists (disease duration < or = 10 years). We investigated the influence of gender and oestrogen status on: (1) age at onset, (2) presenting symptom, (3) severity and progression of motor symptoms (Unified Parkinson's Disease Rating Scale III (UPDRS-III) scores) and (4) amount and progression of nigrostriatal degeneration ([123I]FP-CIT single photon emission computed tomography measurements). RESULTS: Age at onset was 2.1 years later in women (53.4 years) than in men (51.3 years). In women, age at onset correlated positively with parity, age at menopause and fertile life span. Women more often presented with tremor (67%) than men (48%). Overall, patients presenting with tremor had a 3.6 year higher age at onset and a 38% slower UPDRS-III deterioration. Mean UPDRS-III scores at disease onset were equal for both genders, as was the rate of deterioration. Women had a 16% higher striatal [123I]FP-CIT binding than men at symptom onset and throughout the course of PD. CONCLUSIONS: Our results suggest that, in women, the development of symptomatic PD may be delayed by higher physiological striatal dopamine levels, possibly due to the activity of oestrogens. This could explain the epidemiological observations of a lower incidence and higher age at onset in women. Women also presented more often with tremor which, in turn, is associated with milder motor deterioration and striatal degeneration. Taken together, these findings suggest a more benign phenotype in women with PD

Origin of the Mutations in the parkin Gene in Europe: Exon Rearrangements Are Independent Recurrent Events, whereas Point Mutations May Result from Founder Effects

A wide variety of mutations in the parkin gene, including exon deletions and duplications, as well as point mutations, result in autosomal recessive early-onset parkinsonism. Interestingly, several of these anomalies were found repeatedly in unrelated patients and may therefore result from recurrent, de novo mutational events or from founder effects. In the present study, haplotype analysis, using 10 microsatellite markers covering a 4.7-cM region known to contain the parkin gene, was performed in 48 families, mostly from European countries, with early-onset autosomal recessive parkinsonism. The patients carried 14 distinct mutations in the parkin gene, and each mutation was detected in more than one family. Our results support the hypothesis that exon rearrangements occurred independently, whereas some point mutations, found in families from different geographic origins, may have been transmitted by a common founder