One hour-post-load plasma glucose ≥155 mg/dl in healthy glucose normotolerant subjects is associated with subcortical brain MRI alterations and impaired cognition. A pilot study

Background: Glucose alterations are associated with impaired cognition. The 1-h-post-load plasma glucose ≥155mg/dl in non-diabetic subjects confers an increased risk of cardiovascular events and diabetes. This pilot study aimed to investigate whether the 1-h-post-load plasma glucose ≥155 mg/dl negatively affects the subcortical regions of the brain and the cognitive functions. Methods: We enrolled 32 non-diabetic subjects. Patients were divided into two groups based on 1-h- post-load plasma glucose value > or < 155 mg/dl: normal glucose tolerance (NGT) 1-h-high and NGT 1-h-low subjects. All subjects underwent 3 Tesla MRI and standard neuropsychological tests. Results: NGT 1-h-high subjects showed significantly lower values of both right (4.9 ± 0.9 vs. 5.1 ± 0.9ml) and left (4.8 ± 1.1 vs. 5.1 ± 1.1ml) hippocampal hemisphere volume, while right hemisphere hippocampal diffusivity was lower in the NGT 1-h-high group (10.0 ± 0.6 vs. 10.6 ± 0.5 10−4 mm2s−1). NGT 1-h-high subjects also showed a poorer memory performance. In particular, for both Rey Auditory Verbal Learning Task (RAVLT)—immediate-recall and Free and Cued Selective Reminding Test (FCSRT)—delayed total recall, we found lower cognitive test scores in the NGT-1 h-high group (26.5 ± 6.3 and 10.4 ± 0.3, respectively). Conclusions: One-hour-post-load hyperglycemia is associated with morpho-functional subcortical brain alterations and poor memory performance tests

REM-Sleep Behavior Disorder in Patients With Essential Tremor: What Is Its Clinical Significance?

Objective: REM sleep behavior disorder (RBD) is an important risk factor for the dementia development and for the deterioration of autonomic functions in patients with Parkinson's Disease. RBD has also been reported in patients with Essential Tremor (ET). However, its clinical significance in ET remains still unknown. We aimed to investigate clinical, neuropsychological and cardiac autonomic scintigraphic differences between ET patients with and without RBD.Methods: To assess RBD symptoms, RBD Single-Question has been administered in a cohort of 55 patients with a clinical diagnosis of ET. Patients with clinical RBD underwent polysomnography (PSG) confirmation. All patients completed a battery of neuropsychological assessment of memory, executive function, attention, language, and visuospatial function. Cardiac MIBG scintigraphy was performed in order to measure the cardiac autonomic innervation.Results: Ten ET patients (18%) had a PSG-confirmed RBD (ETRBD+). Compared to ET patients without RBD (ETRBD−), significantly reduced scores on memory domain tests such as Rey auditory verbal learning test immediate recall (p = 0.015) and Rey auditory verbal learning test delayed recall (p = 0.004) and phonemic fluency test (p = 0.028) were present in ETRBD+. By contrast, no other significant clinical difference has emerged from the comparison between two ET groups. Similarly, ETRBD+ patients have cardiac MIBG tracer uptake in the normal value range as occurred in those with ETRBD−.Conclusions: This study improves the knowledge on clinical significance of RBD symptoms in ET patients. Our preliminary findings demonstrate that presence of RBD in ET is associated with neurocognitive impairment, but not with cardiac autonomic dysfunction. Further longitudinal studies are needed to investigate whether ET patients with RBD will develop a frank dementia over the time

ANXA1 mutation analysis in Italian patients with early onset PD

: Recently, a novel pathogenic variant in Annexin A1 protein (c.4G > A, p.Ala2Thr) has been identified in an Iranian consanguineous family with autosomal recessive parkinsonism. The deficiencies of ANXA1 could lead to extracellular SNCA accumulation, defects in intracellular signaling pathways and synaptic plasticity causing parkinsonism. The aim of this study was to identify rare ANXA1 variants in 95 early-onset PD patients from South Italy. Sequencing analysis of ANXA1 gene revealed only 2 synonymous variants in PD patients (rs1050305, rs149033255). Therefore, we conclude that the recently published ANXA1 mutation is not a common cause of EOPD in Southern Italy

Clinical phenotype and risk of levodopa-induced dyskinesia in Parkinson’s disease

It is unclear whether patients with different clinical phenotypes of Parkinson’s disease (PD) differ in their risk of developing levodopa-induced dyskinesia. We evaluated the possible association between clinical phenotypes and risk of levodopa-induced dyskinesia in PD patients using a case–control design. The FRAGAMP study is a large Italian multicenter study. Patients affected by PD diagnosed according to the Gelb’s criteria were enrolled and underwent a face-to-face interview. Clinical scales were used to evaluate motor and cognitive impairment. Presence of dyskinesia was assessed by the item 32 of the UPDRS section IV. On the basis of the most prominent motor symptoms at onset PD, patients were classified as tremor-dominant, akinetic-rigid, or mixed type. 485 PD patients (292 men; mean age 65.6 ± 9.8) were enrolled in the study of whom 128 (26.4 %) presented levodopa-induced dyskinesia. Of the 485 patients, 311 (64.1 %) were classified as tremor-dominant, 104 (21.4 %) as Akinetic-Rigid and 70 (14.4 %) as mixed type. Multivariate logistic regression analysis showed a significant negative association between tremor-dominant phenotype and levodopa-induced dyskinesia (adjusted OR 0.48; 95 % CI 0.23–1.00; p value 0.05). When analysis was stratified by age at onset a stronger negative association was found among the late onset (>50 years) PD patients (OR 0.28; 95 % CI 0.11–0.70; p value 0.007) while no association was found among patients with an early onset. Our findings support the hypothesis that the occurrence of resting tremor as an initial manifestation of PD may predict a lower probability of developing levodopa-induced dyskinesia

Diffusivity of Cerebellar Hemispheres Enables Discrimination of Cerebellar or Parkinsonian Multiple System Atrophy from Progressive Supranuclear Palsy–Richardson Syndrome and Parkinson Disease

PURPOSE: To explore the usefulness of histogram analysis of mean diffusivity (MD) derived from diffusion-weighted imaging of large infratentorial structures to distinguish parkinsonian syndromes. MATERIALS AND METHODS: Local research ethics committee approval and informed consent were obtained. Ten patients with Parkinson disease (PD), nine with the parkinsonian variant of multiple system atrophy (MSA-P), seven with the cerebellar variant of MSA (MSA-C), 17 with progressive supranuclear palsy-Richardson syndrome (PSP-RS), and 10 healthy subjects were recruited. Histograms of MD values were generated for all pixels in the whole infratentorial compartment and separately for the whole brainstem, vermis, and cerebellar hemispheres. To assess the differences in MD values among groups, the Kruskal-Wallis test was used, followed by the Mann-Whitney U test for pairwise comparisons. All P values resulting from pairwise comparisons were corrected with the Bonferroni method. RESULTS: MSA-P and MSA-C groups had higher median MD values (P < .01) in the brainstem and cerebellum when compared with other groups; this finding was in line with the known consistent neurodegenerative damage in posterior cranial fossa structures in these diseases. Median MD values from cerebellar hemispheres were used to discriminate patients with MSA-C and those with MSA-P from patients with PD and those with PSP-RS (P < .01; sensitivity, specificity, and positive predictive value equaled 100%). Furthermore, patients with PSP-RS had significantly higher MD values in the vermis than did healthy subjects (P < .05) and patients with PD (P < .001). CONCLUSION: These findings support the clinical usefulness of diffusion imaging in the differential diagnosis of parkinsonism, suggesting that the minimally operator-dependent histogram analysis of the infratentorial structures and particularly of the whole cerebellar hemispheres can be used to distinguish patients with MSA-P and those with MSA-C from patients with PSP-RS and those with PD

Head trauma and Parkinsonâ\u80\u99s disease: results from an Italian case-control study

We evaluated the possible association between head trauma and Parkinsonâ\u80\u99s disease (PD). The FRAGAMP (Fattori di Rischio Ambientali e Genetici Associati alla Malattia di Parkinson) study is a large Italian multicenter case-control study carried out to evaluate the possible role of environmental and genetic factors in PD. Cases and controls were enrolled from six movement disorders centers located in the Central-Southern Italy. A standardized questionnaire was administered to record demographic, epidemiological, and clinical data. Positive history of head trauma was considered only if the head trauma preceded the onset of PD. All cases and controls underwent a standard neurological examination. Adjusted ORs and 95% CI were estimated using multivariate analysis (logistic regression). Four hundred ninety-two PD patients (292 men and 200 women) and 459 controls (160 men and 299 women) were enrolled in the study. A positive history for head trauma was reported by 106 (21.5%) PD patients and by 62 (13.5%) healthy controls. Multivariate analysis (OR adjusted by age, sex, family history, coffee smoking, and alcohol consumption) showed a significant positive association between PD and head trauma with an adjusted OR of 1.50 (95%CI 1.04â\u80\u932.17; p value 0.03). In agreement with literature data, our study supports the positive association between head trauma and PD

Increased risk of depressive and anxiety disorders in relatives of patients with Parkinson disease

Context: Relatives of patients with Parkinson disease (PD) have an increased risk of PD and other neurologic disorders; however, their risk of psychiatric disorders remains uncertain. Objective: To study the risk of depressive disorders and anxiety disorders among first-degree relatives of patients with PD compared with first-degree relatives of controls. Design, Setting, and Participants: In a population-based, historical cohort study, we included 1000 first-degree relatives of 162 patients with PD and 850 first-degree relatives of 147 controls. Both patients with PD and controls were representative of the population of Olmsted County, Minnesota. Main Outcome Measures: Documentation of psychiatric disorders was obtained for each relative separately through a combination of telephone interviews with the relatives (or their proxies) and review of their medical records from a records-linkage system (family study method). Psychiatric disorders were defined using clinical criteria from the DSM-IV or routine diagnoses. Results: We found an increased risk of several psychiatric disorders in first-degree relatives of patients with PD compared with first-degree relatives of controls (hazard ratio [HR], 1.54; 95% confidence interval [CI], 1.21-1.95; P\u3c.001). In particular, we found an increased risk of depressive disorders (HR, 1.45; 95% CI, 1.11-1.89; P=.006) and anxiety disorders (HR, 1.55; 95% CI, 1.05-2.28; P=.03). The results were consistent in analyses that adjusted for type of interview, excluded relatives who developed parkinsonism, or excluded relatives who developed both a depressive disorder and an anxiety disorder. Conclusion: These findings suggest that depressive disorders and anxiety disorders may share familial susceptibility factors with PD. ©2007 American Medical Association. All rights reserved

MR parkinsonism index predicts vertical supranuclear gaze palsy in patients with PSP-parkinsonism

OBJECTIVE: To identify a biomarker for predicting the appearance of vertical supranuclear gaze palsy (VSGP) in patients affected by progressive supranuclear palsy–parkinsonism (PSP-P). METHODS: Twenty-four patients with PSP-P were enrolled in the current study. Patients were clinically followed up every 6 months until the appearance of VSGP or the end of the follow-up (4 years). Participants underwent MRI at baseline and at the end of follow-up. Magnetic resonance parkinsonism index (MRPI), an imaging measure useful for diagnosing PSP, was calculated. RESULTS: Twenty-one patients with PSP-P completed follow-up, and 3 patients dropped out. Eleven of 21 patients with PSP-P developed VSGP after a mean follow-up period of 28.5 months (range 6–48 months), while the remaining 10 patients with PSP-P did not develop VSGP during the 4-year follow-up period. At baseline, patients with PSP-P who later developed VSGP had MRPI values significantly higher than those of patients not developing VSGP without overlapping values between the 2 groups. MRPI showed a higher accuracy (100%) in predicting VSGP than vertical ocular slowness (accuracy 33.3%) or postural instability with or without vertical ocular slowness (accuracy 71.4% and 42.9%, respectively). CONCLUSIONS: Our study demonstrates that MRPI accurately predicted, on an individual basis, the appearance of VSGP in patients with PSP-P, thus confirming clinical diagnosis in vivo