Parkinson's disease is associated with gastrointestinal motility abnormalities favoring the occurrence of local infections. The aim of this study was to investigate whether small intestinal bacterial overgrowth contributes to the pathophysiology of motor fluctuations. Thirty-three patients and 30 controls underwent glucose, lactulose, and urea breath tests to detect small intestinal bacterial overgrowth and Helicobacter pylori infection. Patients also underwent ultrasonography to evaluate gastric emptying. The clinical status and plasma concentration of levodopa were assessed after an acute drug challenge with a standard dose of levodopa, and motor complications were assessed by Unified Parkinson's Disease Rating Scale-IV and by 1-week diaries of motor conditions. Patients with small intestinal bacterial overgrowth were treated with rifaximin and were clinically and instrumentally reevaluated 1 and 6 months later. The prevalence of small intestinal bacterial overgrowth was significantly higher in patients than in controls (54.5% vs. 20.0%; P = .01), whereas the prevalence of Helicobacter pylori infection was not (33.3% vs. 26.7%). Compared with patients without any infection, the prevalence of unpredictable fluctuations was significantly higher in patients with both infections (8.3% vs. 87.5%; P = .008). Gastric half-emptying time was significantly longer in patients than in healthy controls but did not differ in patients based on their infective status. Compared with patients without isolated small intestinal bacterial overgrowth, patients with isolated small intestinal bacterial overgrowth had longer off time daily and more episodes of delayed-on and no-on. The eradication of small intestinal bacterial overgrowth resulted in improvement in motor fluctuations without affecting the pharmacokinetics of levodopa. The relapse rate of small intestinal bacterial overgrowth at 6 months was 43%. © 2013 Movement Disorder Society.

Background: Variants in GBA are the most common genetic risk factor for Parkinson's disease (PD). The impact of different variants on the PD clinical spectrum is still unclear. Objectives: We determined the frequency of GBArelated PD in Italy and correlated GBA variants with motor and nonmotor features and their occurrence over time. Methods: Sanger sequencing of the whole GBA gene was performed. Variants were classified as mild, severe, complex, and risk. β-glucocerebrosidase activity was measured. The Kaplan-Meier method and Cox proportional hazard regression models were performed. Results: Among 874 patients with PD, 36 variants were detected in 14.3%, including 20.4% early onset. Patients with GBA-PD had earlier and more frequent occurrence of several nonmotor symptoms. Patients with severe and complex GBA-PD had the highest burden of symptoms and a higher risk of hallucinations and cognitive impairment. Complex GBA-PD had the lowest β-glucocerebrosidase activity. Conclusions: GBA-PD is highly prevalent in Italy. Different types of mutations underlie distinct phenotypic profiles.

Tremor is one of the clinical manifestations of dystonia; however, there are no specific therapeutic trials evaluating the efficacy of treatments for dystonic tremor (DT), tremor associated with dystonia or primary writing tremor (PWT). We systematically reviewed the literature available up to July 2013 on the treatment of these tremors and retrieved the data of 487 patients published in 43 papers detailing the effects of given interventions on tremor severity. Treatment outcome was highly variable, depending on the specific type of intervention and tremor distribution. No specifically designed studies were available for the treatment of tremor associated with dystonia. As for the other tremors, drug efficacy was generally disappointing and a moderate effect was only found with anticholinergics, tetrabenazine, clonazepam, β-blockers and primidone; levodopa was only efficacious on tremor due to dopa-responsive dystonia. The largest amount of data was available for botulinum toxin injections, which provided a marked improvement, particularly for the management of axial tremors (head or vocal cords). In refractory DTs, deep brain stimulation of several targets was attempted. Deep brain stimulation of globus pallidus internus, thalamus or subthalamic area led to a marked improvement of dystonic axial or appendicular tremors in most cases refractory to other treatments. Few other non-invasive treatments, for example, orthotic device in PWT, have been used with anecdotal success. In conclusion, considering the lack of good-quality studies, future randomised controlled trials are needed. In absence of evidence-based guidelines, we propose an algorithm for the treatment of DT based on currently available data.

Falling is a major clinical problem; especially, in elderly population as it often leads to fractures, immobilization, poor quality of life and life-span reduction. Given the growing body of evidences on the physiopathology of balance disorders in humans, in recent years the approach of research on falls has completely changed and new instruments and new definitions have been formulated. Among them, the definition of "idiopathic faller" (i.e. no overt cause for falling in a given subject) represented a milestone in building the "science of falling". This review deals with the new determinants of the neurobiology of falling: (1) the role of motor impairment and particularly of those "mild parkinsonian signs" frequently detectable in elderly subjects, (2) the role of executive and attentive resources when coping with obstacles, (3) the role of vascular lesions in "highest level gait disorder" (a condition tightly connected with senile gait, cautious gait and frailty), (4) the role of the failure of automaticity or inter-limbs coordination/symmetry during walking and such approach would definitely help the development of screening instrument for subjects at risk (still lacking in present days). This translational approach will lead to the development of specific therapeutic interventions.

Objective:To evaluate the effects of deep brain stimulation of the subthalamic nucleus (STN-DBS) in Parkinson disease (PD) patients on motor complications beyond 15 years after surgery.Methods:Data about motor complications, quality of life (QoL), activities of daily living, the UPDRS motor scores, dopaminergic treatment, stimulation parameters, and side effects of STN-DBS were retrospectively retrieved and compared between before surgery, at 1 year and beyond 15 years after bilateral STN-DBS.Results:Fifty-one patients with 17.06 ± 2.18 years STN-DBS follow-up were recruited. Compared to baseline, the time spent with dyskinesia and the time spent in the off state were reduced by 75% (p<0.001) and by 58.7% (p<0.001), respectively. Moreover, dopaminergic drugs were reduced by 50.6% (p<0.001). The PDQL total score, and the emotional function and social function domains improved of 13.8% (p=0.005), 13.6% (p=0.01) and 29.9% (p<0.001), respectively. Few and mostly manageable device-related adverse events were observed during the follow-up.Conclusions:STN-DBS is still effective beyond 15 years from the intervention, notably with significant improvement in motor complications and stable reduction of dopaminergic drugs. Furthermore, despite the natural continuous progression of PD with worsening of levodopa-resistant motor and non-motor symptoms over the years, STN-DBS patients could maintain an improvement in QoL.Classification of Evidence:This study provides Class IV evidence that, for patients with PD, STN-DBS remains effective at treating motor complications 15 years after surgery.