A Large-Scale Full GBA1 Gene Screening in Parkinson's Disease in the Netherlands.

BACKGROUND: The most common genetic risk factor for Parkinson's disease known is a damaging variant in the GBA1 gene. The entire GBA1 gene has rarely been studied in a large cohort from a single population. The objective of this study was to assess the entire GBA1 gene in Parkinson's disease from a single large population. METHODS: The GBA1 gene was assessed in 3402 Dutch Parkinson's disease patients using next-generation sequencing. Frequencies were compared with Dutch controls (n = 655). Family history of Parkinson's disease was compared in carriers and noncarriers. RESULTS: Fifteen percent of patients had a GBA1 nonsynonymous variant (including missense, frameshift, and recombinant alleles), compared with 6.4% of controls (OR, 2.6; P < 0.001). Eighteen novel variants were detected. Variants previously associated with Gaucher's disease were identified in 5.0% of patients compared with 1.5% of controls (OR, 3.4; P < 0.001). The rarely reported complex allele p.D140H + p.E326K appears to likely be a Dutch founder variant, found in 2.4% of patients and 0.9% of controls (OR, 2.7; P = 0.012). The number of first-degree relatives (excluding children) with Parkinson's disease was higher in p.D140H + p.E326K carriers (5.6%, 21 of 376) compared with p.E326K carriers (2.9%, 29 of 1014); OR, 2.0; P = 0.022, suggestive of a dose effect for different GBA1 variants. CONCLUSIONS: Dutch Parkinson's disease patients display one of the largest frequencies of GBA1 variants reported so far, consisting in large part of the mild p.E326K variant and the more severe Dutch p.D140H + p.E326K founder allele. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC. on behalf of International Parkinson and Movement Disorder Society.

Depressive symptoms in Parkinson's disease are related to decreased hippocampus and amygdala volume.

Depression and anxiety are common in Parkinson's disease (PD), and are among the non-motor symptoms that interfere with quality of life dramatically. Motor, cognitive, and affective features overlap in PD, hampering diagnosis. To shed more light on the contribution of structural brain changes to the presence of PD-related depressive symptoms, we conducted a Voxel-Based Morphometry (VBM) study. We hypothesized that depressive symptoms in PD are related to regional gray matter (GM) volume loss within the limbic circuit. We analyzed the T1-weigthed magnetic resonance imaging (MRI) images of 67 PD patients with a mean disease duration of 2.95 (±3.39) years. Scores on the Beck Depression Inventory (BDI) and GM probability maps were analyzed by regression analysis to study the association between GM volume and severity of depressive symptoms. Results are reported at both the uncorrected and the family-wise error (FWE) corrected level for multiple comparisons. The BDI scores correlated negatively with bilateral hippocampus and right amygdala volume and positively with the volume of the anterior cingulate cortex. These findings confirm the hypothesized involvement of the limbic circuit in PD-related depressive symptoms. We speculate that non-dopaminergic changes are essential in the pathophysiology of depressive symptoms in PD, because our findings suggest the involvement of extra-striatal brain regions.

Rivastigmine for minor visual hallucinations in Parkinson's disease: A randomized controlled trial with 24 months follow-up.

BACKGROUND: Visual hallucinations are common in patients with Parkinson's disease and represent probably the major independent predictor for cognitive deterioration and nursing home placement. OBJECTIVE: To investigate if treatment of minor visual hallucinations in Parkinson's disease with rivastigmine delays the progression to psychosis. METHODS: A multicenter, randomized, double-blind, placebo-controlled trial was conducted which aimed to recruit 168 patients with Parkinson's disease reporting minor visual hallucinations 4 weeks before it. Important exclusion criteria were Parkinson's disease dementia, current delirium, and treatment with antipsychotics or drugs that have significant anti-cholinergic side effects. Subjects were randomized to rivastigmine capsules, 3-6 mg twice a day, or placebo for 24 months. The primary outcome was the time to Parkinson's disease psychosis, which was defined as the need to start with antipsychotics. RESULTS: The trial was stopped prematurely because of slow recruitment. Ninety-one patients were randomized: 46 patients were assigned to rivastigmine and 45 patients to placebo. No effect of rivastigmine could be demonstrated on the transition time to psychosis or dementia during the 24-month follow-up period. After 6 months of study treatment, cognition, mood, motor performance, and non-motor performance did not differ significantly between the rivastigmine-group and the placebo-group. CONCLUSIONS: Because the study was terminated early, it was insufficiently powered to properly evaluate the primary outcome. The limited data of the study favor a wait and see approach instead of early treatment with rivastigmine in PD patients with minor VH.

The Active Recovery Triad Model: A New Approach in Dutch Long-Term Mental Health Care.

Unlike developments in short-term clinical and community care, the recovery movement has not yet gained foothold in long-term mental health services. In the Netherlands, approximately 21,000 people are dependent on long-term mental health care and support. To date, these people have benefited little from recovery-oriented care, rather traditional problem-oriented care has remained the dominant approach. Based on the view that recovery is within reach, also for people with complex needs, a new care model for long-term mental health care was developed, the active recovery triad (ART) model. In a period of 2.5 years, several meetings with a large group of stakeholders in the field of Dutch long-term mental health care took place in order to develop the ART model. Stakeholders involved in the development process were mental health workers, policy advisors, managers, directors, researchers, peer workers, and family representatives. The ART model combines an active role for professionals, service users, and significant others, with focus on recovery and cooperation between service users, family, and professionals in the triad. The principles of ART are translated into seven crucial steps in care and a model fidelity scale in order to provide practical guidelines for teams implementing the ART model in practice. The ART model provides guidance for tailored recovery-oriented care and support to this "low-volume high-need" group of service users in long-term mental health care, aiming to alter their perspective and take steps in the recovery process. Further research should investigate the effects of the ART model on quality of care, recovery, and autonomy of service users and cooperation in the triad.

[Swallowing and suffocating: respiratory consequences of chlorine and hydrocarbons]. / Slikken en stikken?

Several toxic substances, inhaled or swallowed, can cause similar respiratory symptoms. We present two young patients with respiratory symptoms, one after inhaling chlorine gas and the other after ingesting lamp oil. Pathophysiology and clinical effects of these two substances differ. No specific antidotes exist for most toxic substances. Inhalation of respiratory irritants, such as chlorine gas, can lead to wheezing or bronchial obstruction, which can generally be handled by the family physician. In mild cases, administration of a bronchodilator is sufficient. Hydrocarbons such as lamp oil, however, can cause severe respiratory problems which develop over days, even when only small amounts are ingested. Hospitalization is therefore warranted in these cases, even when initial symptoms appear to be mild.

[Iodine deficiency due to an abnormal diet]. / Jodiumdeficiëntie door afwijkend voedingspatroon.

BACKGROUND: In the past, iodine deficiency was an important cause of goitre and mental retardation. Since the introduction of iodised salt the incidence of iodine deficiency has declined enormously. CASE DESCRIPTION: An 8-year old girl had goitre for several months. Her diet was modified to take into account supposed food allergies. She never ate bread products and no salt was added to the food on the assumption that salt is harmful. The thyroid stimulating hormone (TSH) level was not abnormal, the free T4 value was reduced and the T3 value high to normal. Urine investigation indicated reduced iodine excretion. Echography demonstrated a diffusely enlarged thyroid. The iodine deficiency was successfully treated with oral iodine supplementation. CONCLUSION: This case report shows that iodine deficiency based on an inadequate iodine intake still occurs in the Netherlands. An increase in supposed allergies and subsequent decrease of iodine supplementation in the diet may lead to a higher frequency of this "forgotten" disease.