Motor and non-motor features in Parkinson's Disease patients carrying GBA gene mutations.

BACKGROUND: Mutations of the Glucocerebrosidase (GBA) gene are the most common genetic risk factor yet discovered for Parkinson's Disease (PD), being found in about 5-14% of Caucasian patients. OBJECTIVE: We aimed to assess motor and non-motor symptoms (NMS) in patients with GBA-related PD (GBA-PD) in comparison with idiopathic PD (iPD) subjects using standardized and validated scales. METHODS: Eleven (4 M, 7 F) patients with GBA-PD and 22 iPD patients, selected from the same cohort and matched for gender, age, and disease duration, were enrolled. The disease severity was assessed by Unified Parkinson's Disease Rating Scale-section III, gait disorder and falls by Freezing of Gait Questionnaire, and motor fluctuations by Wearing off questionnaire. NMS were evaluated using the following scales: Mini-Mental State Examination and extended neuropsychological battery, if required, Non-Motor Symptoms Scale, SCOPA-AUT Questionnaire, Apathy Evaluation Scale, Beck Depression Inventory, Epworth Sleepiness Scale, Restless Legs Syndrome Rating Scale, REM Sleep Behavior Disorder Screening Questionnaire, and Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease. RESULTS: GBA-PD patients showed a more severe and rapidly progressive disease, and more frequent positive family history for PD, akinetic-rigid phenotype, postural instability, dementia, and psychosis in comparison to iPD. Two of three subjects carrying L444P mutation presented with early dementia. We also found a higher occurrence of fatigue, diurnal sleepiness, and intolerance to heat/cold in the carriers group. CONCLUSIONS: Our results confirm that NMS and a more severe and faster disease course more frequently occur among GBA-PD patients in comparison to iPD.

Screening for Fabry disease in a series of Parkinson's disease patients and literature review.

BACKGROUND: So far, mutations in genes encoding lysosomal enzymes have been associated with Parkinson's disease (PD). Fabry disease (FD) is an X-linked lysosomal storage disease caused by alpha-galactosidase A (α-GAL) deficiency, leading to deposition of globotriaosylceramide in the nervous system and other organs. We aimed to screen for FD a case series of PD patients from Southern Italy and to review the literature. METHODS: One hundred and forty-four consecutive unrelated PD subjects were enrolled. The α-GAL activity was measured in all men and, in case of pathological values, subsequent determination of globotriaosylsphingosine (lyso-Gb3) and GLA gene sequencing were also performed. All the women underwent GLA gene sequencing. RESULTS: α-GAL levels resulted low in fifteen men, whereas lyso-Gb3 testing showed values within the reference range in all of them. GLA gene variants were not detected in any tested subjects. One pathological study, six case series, and five case reports are currently reported in literature. CONCLUSIONS: The few studies reviewed are heterogeneous, and the results are controversial. An unknown significance variant in GLA gene was detected in PD patients in one large study, whereas decreased α-GAL activity was observed in PD subjects in two other researches, but without confirmation by lyso-Gb3 assessment or genetic analysis. Vascular parkinsonism was associated to FD in five case reports. We found no association between PD and FD in our population. However, it is not possible to draw definitive conclusions due to limited sample size. Furthermore, controls would have been missing in case of a positive finding.

Prevalence and features of non-motor symptoms in Wilson's disease.

INTRODUCTION: Wilson's Disease (WD) is an autosomal recessive disorder caused by excessive copper deposition in liver, brain and other organs. The clinical picture is characterized by hepatic, psychiatric and neurological dysfunction. Movement disorders are the core neurological features, although non-motor symptoms (NMS), as cognitive/affective, autonomic and sleep disorders, may occur over time. We aimed to assess the frequency of NMS in WD patients compared with healthy subjects. METHODS: Twenty-seven patients affected with genetically proven WD (12 F, 15 M) and 35 healthy controls (Ctrl; 17 F, 18 M), comparable for age and education, were enrolled. Eighteen patients presented with the neurological form of the disease (NV) and nine with the non-neurological variant (NNV). NMS were assessed in all subjects by the following clinical scales: Mini-Mental State Examination (MMSE), Non-Motor Symptoms Scale (NMSS), SCOPA-AUT Questionnaire, Apathy Evaluation Scale (AES), Beck Depression Inventory (BDI), Epworth Sleepiness Scale (ESS), Restless Legs Syndrome Rating Scale (RLSRS), REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ), Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease (QUIP-RS). RESULTS: We found that the patients showed more severe and frequent NMS and daytime sleepiness, and lower MMSE than Ctrl. In comparison to healthy subjects, NV subjects showed statistically significant higher ESS, NMSS, and RLSRS scores, and a lower MMSE score. Subtle and subclinical extrapyramidal/pyramidal signs and brain MRI signal abnormalities were detected in patients considered as asymptomatic for neurological disturbances. CONCLUSIONS: NMS are common among WD patient, in particular those with NV, likely due to the widespread pathological changes throughout the central nervous system.

Autonomic disorders and myocardial 123I-metaiodobenzylguanidine scintigraphy in Huntington's disease.

BACKGROUND: Huntington's disease (HD) patients often present with abnormal modulation of blood pressure and heart rate. We investigated whether cardiac autonomic innervation assessed by 123I-metaiodobenzylguanidine (MIBG) imaging is impaired in HD patients, in comparison with controls (Ctrl). METHODS: Fifteen patients (6 F and 9 M) were assessed by the motor section of the Unified HD Rating Scale, the Total Function Capacity, and the scale for outcomes in Parkinson's disease-autonomic (SCOPA-AUT) questionnaire. All patients and 10 Ctrl (5 F and 5 M) underwent 123I-MIBG imaging. From planar images, the early and late heart-to-mediastinum (H/M) ratios and myocardial washout rates (WR) were calculated. RESULTS: We did not find significant differences in early and late H/M ratios and WR between the two groups. At individual level, three patients showed reduced early and/or late H/M ratios. The most common autonomic complaints were gastrointestinal and genitourinary disorders. SCOPA-AUT questionnaire score results positively correlated with the disease duration and WR. CONCLUSIONS: Our study indicates that myocardial postganglionic sympathetic innervation is essentially preserved or only minimally involved in HD. These findings suggest that the cardiovascular dysfunction might be mainly due to the impairment of brain areas associated with the regulation and modulation of the heart function.

Othello syndrome in Parkinson's disease: a systematic review and report of a case series.

INTRODUCTION: Psychosis in Parkinson's disease (PD) is common and consists of hallucinations, illusions, and delusions. Among the latter, delusional jealousy, also named Othello syndrome (OS), might impair the quality of life of both patients and their partners. We aimed to perform a systematic review and report a series of PD patients presenting with OS. METHODS: A systematic review research was performed in PubMed database, excluding non-English articles, single case reports, reviews and neuropathology articles, comments, and articles concerning OS associated with deep brain stimulation (DBS) and levodopa-carbidopa intestinal gel infusion. We also described eleven PD patients (9 M and 2 F) with OS, identified in a cohort of consecutive 153 patients, comparing them with eleven matched no OS (nOS) PD subjects taken from the same cohort. RESULTS: We included eight articles (four case series and four cross-sectional studies). OS resulted more common among males than females. We did not find higher levodopa dose and levodopa equivalent dose for dopamine agonists and for all anti-parkinsonian drugs in our OS group. In our case series, OS patients showed visual hallucinations (p=0.001) and a trend to have depression (p=0.080) more frequently than nOS ones. CONCLUSIONS: OS is not a rare disorder in PD, probably due not only to abnormal dopaminergic stimulation but also to serotonergic dysfunction in biologically predisposed subjects. Visual hallucinations and other concomitant psychiatric diseases, in particular depression, might represent a risk factor for the OS development.