Grigioni Foundation for Parkinson's disease

Deep brain stimulation (DBS) is established for Parkinson's disease (PD), but conventional DBS (cDBS) may yield suboptimal symptom control and side effects, particularly on gait. Adaptive DBS (aDBS), adjusting stimulation to subthalamic beta activity, may offer superior outcomes, though programming remains incompletely defined. Between January and April 2025, we offered dual threshold aDBS to 20 consecutive PD patients with chronic cDBS and a Percept neurostimulator. Nine were eligible; exclusions were due to signal artifacts, absence of a distinct beta peak, or stimulation settings incompatible with aDBS. By July 2025, five remained on chronic aDBS, one reverted to cDBS by preference, and three were still in optimization. In this manuscript, we outline our aDBS programming principles and preliminary clinical efficacy. On unblinded MDS-UPDRS III, aDBS yielded a ~35% greater motor improvement than cDBS, with gait showing the most consistent benefits. Dual threshold aDBS appears clinically advantageous, though current technical and programming constraints may limit widespread adoption.

Background and ObjectiveRecently, RAB32 has been identified as possibly linked to Parkinson's disease. We studied the prevalence and clinical correlates of the p.Ser71Arg variant in the RAB32 gene in a large case series of Italian patients with Parkinson's disease or atypical parkinsonism.MethodsA single‐center cohort with a case‐control component (consecutively collected at the Parkinson Institute of Milan between 2002 and 2023) was screened for the RAB32 p.Ser71Arg variant. Detailed clinical characteristics of carriers were reviewed. Healthy control subjects were partners or unrelated caregivers. The variant was detected by a TaqMan polymerase chain reaction assay.ResultsA total of 4600 patients (3762 with PD and 838 with atypical parkinsonisms) and 1722 healthy control subjects were consecutively included in the study. We identified 20 new variant carriers that, together with the 8 previously identified, had younger age at onset than noncarriers (51.0 ± 10.7 vs. 58.3 ± 11.0 years, respectively; P = 0.01). All carriers had a good response to dopaminergic therapy and device‐aided therapies. Carriers had mild or no cognitive decline and mild or no depressive symptoms; six had impulse control disorders and one a REM behavior disorder. Family history was positive in 55.5% of cases versus 22.0% of patients without the variant (P < 0.001) and was compatible with a dominant pattern of inheritance. The variant was not identified in patients with atypical parkinsonisms.ConclusionsThis study confirms that RAB32 is associated with a relatively young adult‐onset PD with a favorable therapeutic response. This variant should be included in genetic panels used for the diagnosis of familial and/or relatively young‐onset PD. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

BackgroundAnosognosia (unawareness) of choreic movements is relatively common in Huntington’s disease (HD) although its origin is unclear.AimsWe investigated anosognosia of motor deficits in HD.MethodsSeventy-one outpatients with stage I or II HD participated. The motor section of UHDRS, the total functional capacity, a short battery of cognitive tests, the SANS and SAPS scales for negative and positive psychiatric symptoms, and the Hamilton scales for depression and anxiety were administered. A semi-structured four-point questionnaire was also administered to assess extent of motor anosognosia in daily life.ResultsThe patients were divided into 27 (38%) (group 1) aware of their motor symptoms (score zero on questionnaire), and 44 (62%) (group 2) with various degrees of unawareness: 29 (66%) group 2 patients scored 1, 11 (25%) scored 2, and 4 (9%) scored 3. The two groups were compared. Group 2 patients performed worse on visual search test (p = 0.04) and SANS (p = 0.02). Anosognosia correlated directly with UHDRS (r=0.32; p=0.04) and indirectly with anxiety (r=−0.33; p=0.03). When shown their motor impairments, the 4 patients with score 3 retained the delusional belief they had no impairment.ConclusionsTwo thirds of our patients had motor anosognosia, with higher SANS score, indicating more severe apathetic syndrome, and worse visual search test, indicating slower cognitive processing, than non-anosognosic patients. The finding of delusional belief in patients with severe anosognosia suggests that psychiatric changes play a role in generating anosognosia in HD. HD anosognosia appears to have varied origins.

Differences in gut microbiota between Parkinson's disease patients and controls seem to depend on multiple-frequently unmeasured-confounders. Monozygotic twins offer a unique model for controlling several factors responsible for interpersonal variation in gut microbiota. Fecal samples from 20 monozygotic twin pairs (n=40) discordant for Parkinson's disease were studied (metagenomic shotgun analysis). Paired data analysis detected minimal differences in bacterial taxa abundance at species level (Bacteroides pectinophilus [p=0.037], Bifidobacterium pseudocatenulatum [p= 0.050], and Bifidobacterium catenulatum [p=0.025]) and in predicted metabolic pathways (primary bile acid biosynthesis [p=0.037]). Additional studies are warranted to understand the role of gut microbiota in the pathogenesis of Parkinson's disease. ANN NEUROL 2022;92:631-636.

Previous prospective studies highlighted dairy intake as a risk factor for Parkinson's disease (PD), particularly in men. It is unclear whether this association is causal or explained by reverse causation or confounding. The aim is to examine the association between genetically predicted dairy intake and PD using two-sample Mendelian randomization (MR). We genotyped a well-established instrumental variable for dairy intake located in the lactase gene (rs4988235) within the Courage-PD consortium (23 studies; 9823 patients and 8376 controls of European ancestry). Based on a dominant model, there was an association between genetic predisposition toward higher dairy intake and PD (odds ratio [OR] per one serving per day=1.70, 95% confidence interval=1.12-2.60, P=0.013) that was restricted to men (OR=2.50 [1.37-4.56], P=0.003; P-difference with women=0.029). Using MR, our findings provide further support for a causal relationship between dairy intake and higher PD risk, not biased by confounding or reverse causation. Further studies are needed to elucidate the underlying mechanisms. © 2022 International Parkinson and Movement Disorder Society.