Our understanding of dysfunction of the gastrointestinal system in patients with Parkinson's disease has increased substantially in the past decade. The entire gastrointestinal tract is affected in these patients, causing complications that range from oral issues, including drooling and swallowing problems, to delays in gastric emptying and constipation. Additionally, small intestinal bacterial overgrowth and Helicobacter pylori infection affect motor fluctuations by interfering with the absorption of antiparkinsonian drugs. The multifaceted role of the gastrointestinal system in Parkinson's disease necessitates a specific and detailed assessment and treatment plan. The presence of pervasive α-synuclein deposition in the gastrointestinal tract strongly implicates this system in the pathogenesis of Parkinson's disease. Future studies elucidating the role of the gastrointestinal tract in the pathological progression of Parkinson's disease might hold potential for early disease detection and development of neuroprotective approaches.

Deep brain stimulation of the subthalamic nucleus represents the most important innovation for treatment of advanced Parkinson's disease. Prospective studies have shown that although the beneficial effects of this procedure are maintained at 5 years, axial motor features and cognitive decline may occur in the long term after the implants. In order to address some unsolved questions raised by previous studies, we evaluated a series of 20 consecutive patients who received continuous stimulation for 8 years. The overall motor improvement reported at 5 years (55.5% at Unified Parkinson's Disease Rating Scale-motor part, P < 0.001 compared with baseline) was only partly retained 3 years later (39%, P < 0.001, compared with baseline; -16.5%, P < 0.01, compared with 5 years), with differential effects on motor features: speech did not improve and postural stability worsened (P < 0.05). The preoperative levodopa equivalent daily dose was reduced by 58.2% at 5 years and by 60.3% at 8 years. In spite of subtle worsening of motor features, a dramatic impairment in functional state (-56.6% at Unified Parkinson's Disease Rating Scale-Activities of Daily Living, P < 0.01) emerged after the fifth year of stimulation. The present study did not reveal a predictive value of preoperative levodopa response, whereas few single features at baseline (such as gait and postural stability motor scores and the preoperative levodopa equivalent daily dose) could predict long-term motor outcome. A decline in verbal fluency (slightly more pronounced than after 5 years) was detected after 8 years. A significant but slight decline in tasks of abstract reasoning, episodic memory and executive function was also found. One patient had developed dementia at 5 years with further progression at 8 years. Executive dysfunction correlated significantly with postural stability, suggesting interplay between axial motor deterioration and cognition. Eight years after surgery, no significant change was observed on scales assessing depression or anxiety when compared with baseline. At 8 years, there was no significant increase of side-effects when compared with 5-year follow-up. In conclusion, deep brain stimulation of the subthalamic nucleus is a safe procedure with regard to cognitive and behavioural morbidity over long-term follow-up. However, the global benefit partly decreases later in the course of the disease, due to progression of Parkinson's disease and the appearance of medication- and stimulation-resistant symptoms.

Acute necrotizing encephalopathy (ANE) is a rapidly progressive encephalopathy that can occur in otherwise healthy children after common viral infections such as influenza and parainfluenza. Most ANE is sporadic and nonrecurrent (isolated ANE). However, we identified a 7 Mb interval containing a susceptibility locus (ANE1) in a family segregating recurrent ANE as an incompletely penetrant, autosomal-dominant trait. We now report that all affected individuals and obligate carriers in this family are heterozygous for a missense mutation (c.1880C-->T, p.Thr585Met) in the gene encoding the nuclear pore protein Ran Binding Protein 2 (RANBP2). To determine whether this mutation is the susceptibility allele, we screened controls and other patients with ANE who are unrelated to the index family. Patients from 9 of 15 additional kindreds with familial or recurrent ANE had the identical mutation. It arose de novo in two families and independently in several other families. Two other patients with familial ANE had different RANBP2 missense mutations that altered conserved residues. None of the three RANBP2 missense mutations were found in 19 patients with isolated ANE or in unaffected controls. We conclude that missense mutations in RANBP2 are susceptibility alleles for familial and recurrent cases of ANE.