The European Huntington's Disease Network (EHDN) commissioned an international task force to provide global evidence-based recommendations for everyday clinical practice for treatment of Huntington's disease (HD). The objectives of such guidelines are to standardize pharmacological, surgical and non-pharmacological treatment regimen and improve care and quality of life of patients. A formalized consensus method, adapted from the French Health Authority recommendations was used. First, national committees (French and English Experts) reviewed all studies published between 1965 and 2015 included dealing with HD symptoms classified in motor, cognitive, psychiatric, and somatic categories. Quality grades were attributed to these studies based on levels of scientific evidence. Provisional recommendations were formulated based on the strength and the accumulation of scientific evidence available. When evidence was not available, recommendations were framed based on professional agreement. A European Steering committee supervised the writing of the final recommendations through a consensus process involving two rounds of online questionnaire completion with international multidisciplinary HD health professionals. Patients' associations were invited to review the guidelines including the HD symptoms. Two hundred and nineteen statements were retained in the final guidelines. We suggest to use this adapted method associating evidence base–medicine and expert consensus to other rare diseases.

The effect of oral N-acetyl-L-cysteine (NAC) on plasma sulphhydryls has been studied in healthy volunteers. Following NAC 30 mg.kg-1, total NAC in plasma (i.e. free NAC and NAC as disulphides) reached a median peak concentration of 67 nmol.ml-1 within 45 to 60 min, and disappeared with an apparent half-life of 1.3 h. Only a fraction of total NAC (AUC 163 nmol.ml-1.h) was in the form of free NAC (AUC 12 nmol.ml-1.h, peak concentration 9 nmol.ml-1). Free cysteine was markedly increased (peak increment 49 nmol.ml-1; AUC 80 nmol.ml-1.h). Total cysteine and free and total glutathione in plasma were unchanged. Following the administration of 2 g paracetamol plasma cysteine and glutathione decreased (median decrement in AUC over 3 h was 5.1 nmol.ml-1.h and 3.8 nmol.ml-1.h, respectively). In contrast, the administration of 2 g NAC together with paracetamol resulted in an increase in the AUC of cysteine (+29.2 nmol.ml-1.h) and glutathione (+4.6 nmol.ml-1.h). The data show that NAC leads to a marked increase in circulating cysteine, in part by reacting with cystine and thereby forming mixed disulphides with cysteine and releasing free cysteine as shown in vitro. NAC had no effect on plasma glutathione in the absence of increased stress on the glutathione pools. However, NAC supports glutathione synthesis when the demand for glutathione is increased, as during the metabolism of paracetamol.

We and others found two polymorphic LRRK2 (leucine-rich repeat kinase 2) variants (rs34778348:G>A; p.G2385R and rs33949390:G>C; p.R1628P) associated with Parkinson disease (PD) among Chinese patients, but the common worldwide rs34637584:G>A; p.G2019S mutation, was absent. Focusing exclusively on Han Chinese, we first sequenced the coding regions in young onset and familial PD patients and identified 59 variants. We then examined these variants in 250 patients and 250 control subjects. Among the 17 polymorphic variants, five demonstrated different frequency in cases versus controls and were considered in a larger sample of 1,363 patients and 1,251 control subjects. The relative risk of an individual with both p.G2385R and p.R1628P is about 1.9, and this is reduced to 1.5-1.6 if the individual also carries rs7133914:G>C; p.R1398H or rs7308720:C>A: p.N551K. The risk of a carrier with p.R1628P is largely negated if the individual also carries p.R1398H or p.N551K. In dopaminergic neuronal lines, p.R1398H had significantly lower kinase activity, whereas p.G2385R and p.R1628P showed higher kinase activity than wild type. We provided the first evidence that multiple LRRK2 variants exert an individual effect and together modulate the risk of PD among Chinese.

Patients with a predominantly choreatic motor phenotype performing better in all areas than patients with a hypokinetic-rigid motor phenotype.