The contribution of genes to etiology is variable for different movement disorders. Some diseases are by definition genetic, such as Huntington’s disease. Other disorders such as Parkinson’s disease may have monogenic causes but are largely the result of nongenetic factors. Dystonia and the atypical parkinsonisms have high genetic burdens in their etiologies, with reduced penetrance being a common feature. I review the clinical and molecular features and genotype-phenotype correlations in monogenic causes of autosomal dominant (SNCA, LRRK2, VPS35) and recessive (PARKIN, PINK1, DJ-1) Parkinson disease, and of isolated (TOR1A, THAP1, GNAL) and combined (GCH1, TH, ATP1A3, PRKRA, TAF1, SGCE) dystonia. Because the genetics of movement disorders is complex, genetic testing in aid of clinical diagnosis can only be recommended for genes that are unequivocally disease causing. However, gene panel testing is slowly transitioning into clinical utility, heralding the transition of movement disorder genetics from bench to bedside. This is a shortened version of a book chapter on movement disorder genetics.

BACKGROUND: Several trials have raised the possibility that specific antihypertensives give protection against stroke beyond the effect seen with blood pressure reduction. In previous studies, ACE inhibitors have been shown to reduce both first and recurrent strokes. Angiotensin receptor blockers have shown benefit in the primary prevention, but evidence for secondary prevention is lacking.

OBJECTIVES: The primary objective is to determine if antihypertensive treatment with ARBs compared with other antihypertensive therapy decreases the risk of vascular events in patients with previous stroke. Secondary outcomes include risk for cerebrovascular events, for cardiovascular events, and overall mortality.

METHODS: Data from randomised controlled comparisons an ARB-based antihypertensive regimen with non-ARB-based treatment, administered to patients with previous cerebrovascular event, and where outcomes include stroke recurrence, were included. Meta-analysis was performed using the fixed effects model. Treatment effect was measured using the Mantel Haenszel Risk Ratio using a 95% confidence interval.

RESULTS: Five studies met the inclusion criteria. Two studies were primarily trials of antihypertensive therapy on patients with previous stroke, two studies were subgroup analyses, and one study was a Phase II trial of hypertension treatment in acute stroke. Treatment with ARBs was associated with statistically significant reductions in the risk for vascular events (RR 0.90, 95% CI 0.85 to 0.96), recurrent stroke (RR 0.91, 95% CI 0.84 to 0.98), and cardiovascular events (RR 0.90, 95% CI 0.82 to 0.98). There was no effect on mortality.

CONCLUSIONS: The evidence from this review supports the use of antihypertensive therapy using ARBs in patients with previous cerebrovascular events. Treatment with such is shown to significantly reduce all vascular events post-stroke, and spear reduce the risk of recurrent stroke and the occurrence of cardiovascular morbidity, although there is no effect on mortality.

 

Human ; Humans ; Antihypertensive Agents ; Angiotensin Receptor Antagonists ; Angiotensin-converting Enzyme Inhibitors ; Odds Ratio ; Secondary Prevention ; Confidence Intervals ; Blood Pressure ; Stroke ; Hypotension ; Risk ; Primary Prevention ; Hypertension