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1.
Gait Posture ; 108: 199-207, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37993298

ABSTRACT

BACKGROUND: Freezing of gait (FoG) is an episodic failure of gait exposing people with Parkinson's disease (PD) to a high risk of falling. Despite growing evidence of the interconnection between impaired trunk control and FoG, a detailed description of spinal kinematics during walking is still lacking in this population. RESEARCH QUESTION: Do spinal alterations impact gait performance in individuals with PD and FoG? METHODS: We analyzed kinematic data of 47 PD participants suffering (PD-FOG, N = 24) or not suffering from FoG (PD-NFOG, N = 23) and 15 healthy controls (HCO) during quiet standing and unperturbed walking. We estimated the main spinal variables (i.e., spinal length, lordosis and kyphosis angles, trunk inclination), the pelvis angles, and the shoulder-pelvis angles during gait and standing. We studied differences across conditions and groups and the relationships between postural and gait parameters using linear regression methods. RESULTS: During standing and walking, both PD groups showed increased trunk inclination and decreased lordosis angle with respect to HCO, as well as a decreased range in variation of kyphosis angle, pelvic obliquity, and shoulder-pelvis angles. Only PD-FOG participants showed reduced range of lordosis angle and spinal length compared to HCO. PD-FOG individuals were also not able to straighten their spine during walking compared to standing. Stride length and velocity were decreased in both patient groups compared to HCO, while swing duration was reduced only in the PD-FOG group. In individuals with FoG, trunk inclination and lordosis angle showed moderate but significant positive correlations with all gait alterations. SIGNIFICANCE: Spine alterations impacted gait performance in individuals with PD suffering from FoG. Excessive trunk inclination and poor mastering of the lordosis spinal region may create an unfavourable postural precondition for forward walking. Physical therapy should target combined spinal and stepping alterations in these individuals.


Subject(s)
Gait Disorders, Neurologic , Kyphosis , Lordosis , Parkinson Disease , Humans , Parkinson Disease/complications , Parkinson Disease/therapy , Biomechanical Phenomena , Gait Disorders, Neurologic/etiology , Gait , Walking
2.
Eur J Radiol ; 109: 95-100, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30527319

ABSTRACT

OBJECTIVES: The Nigrosome-1 and putaminal hypointensity depicted on susceptibility-weighted imaging (SWI), and midbrain atrophy assessed on T1-weighted are some of the most common radiological parameters to diagnose Parkinsonism at Magnetic Resonance (MR) imaging. Our aim is to assess the feasibility of these signs in the differentiation of Idiopathic Parkinson's disease (IPD) patients versus disease (DC) and healthy controls (HC) and in the assessment of the Atypical Progressive Parkinsonisms (APPs). METHODS: Presence or loss of the Nigrosome-1 was assessed retrospectively on multiple-echo SWI obtained on a 3 T scan by two neuroradiologists. Results were compared with the 123I-FP-CIT SPECT images. Morphologic diagnostic features suggestive of APPs such as midbrain atrophy and putaminal hypointensity were evaluated by qualitative scores. The midbrain and putaminal scores were summed (combined score) and then added to the Nigrosome-1 score (global score). RESULTS: The study included 126 patients with IPD (n = 56), APPs patients (n = 30; 18 PSP, 3 MSA-C, 9 MSA-P), 16 DC and 24 HC. Sensitivity and specificity of the Nigrosome-1 in discriminating IPD from controls were 96,43% and 85.00%, APPs from controls were 100% and 85%, IPD from APPs were 96,43% and 0% respectively. Combined score for midbrain atrophy and putaminal hypointensity resulted in the most accurate for distinguishing APPs from IPD with a value of ≥ 2 (AUC = 0.98). CONCLUSION: Nigrosome-1 is a valid tool to differentiate IPD-APPs from controls. The combined score of midbrain atrophy and putaminal hypointensity represents a valid diagnostic pointer in the differential diagnosis of APPs from IPD.


Subject(s)
Dopaminergic Neurons/pathology , Parkinsonian Disorders/diagnosis , Aged , Diagnosis, Differential , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Multiple System Atrophy/diagnosis , Parkinson Disease/diagnosis , Parkinson Disease/pathology , Retrospective Studies , Sensitivity and Specificity , Tomography, Emission-Computed, Single-Photon/methods
3.
Eur J Neurol ; 22(8): 1184-91, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25962410

ABSTRACT

BACKGROUND AND PURPOSE: Depressed mood is a common psychiatric problem associated with Parkinson's disease (PD), and studies have suggested a benefit of rasagiline treatment. METHODS: ACCORDO (see the ) was a 12-week, double-blind, placebo-controlled trial to evaluate the effects of rasagiline 1 mg/day on depressive symptoms and cognition in non-demented PD patients with depressive symptoms. The primary efficacy variable was the change from baseline to week 12 in depressive symptoms measured by the Beck Depression Inventory (BDI-IA) total score. Secondary outcomes included change from baseline to week 12 in cognitive function as assessed by a comprehensive neuropsychological battery; Parkinson's disease quality of life questionnaire (PDQ-39) scores; Apathy Scale scores; and Unified Parkinson's Disease Rating Scale (UPDRS) subscores. RESULTS: One hundred and twenty-three patients were randomized. At week 12 there was no significant difference between groups for the reduction in total BDI-IA score (primary efficacy variable). However, analysis at week 4 did show a significant difference in favour of rasagiline (marginal means difference ± SE: rasagiline -5.46 ± 0.73 vs. placebo -3.22 ± 0.67; P = 0.026). There were no significant differences between groups on any cognitive test. Rasagiline significantly improved UPDRS Parts I (P = 0.03) and II (P = 0.003) scores versus placebo at week 12. Post hoc analyses showed the statistical superiority of rasagiline versus placebo in the UPDRS Part I depression item (P = 0.04) and PDQ-39 mobility (P = 0.007) and cognition domains (P = 0.026). CONCLUSIONS: Treatment with rasagiline did not have significant effects versus placebo on depressive symptoms or cognition in PD patients with moderate depressive symptoms. Although limited by lack of correction for multiple comparisons, post hoc analyses signalled some improvement in patient-rated cognitive and depression outcomes.


Subject(s)
Depression/drug therapy , Indans/pharmacology , Neuroprotective Agents/pharmacology , Parkinson Disease/drug therapy , Aged , Depression/etiology , Double-Blind Method , Female , Humans , Indans/administration & dosage , Male , Middle Aged , Neuroprotective Agents/administration & dosage , Parkinson Disease/complications , Treatment Outcome
5.
Parkinsonism Relat Disord ; 20(1): 32-6, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24084382

ABSTRACT

The Movement Disorders Society (MDS) formulated diagnostic criteria and assessment guidelines for the screening of dementia in Parkinson's disease (PD). We carried out a validation of the cognitive measures suggested in the screening algorithm (i.e. the Mini Mental State Examination - MMSE - total score, serial 7s subtraction, 3-word recall, pentagons copy, and one minute letter fluency) in 86 patients with PD. Thirty-six percent of participants were diagnosed with dementia using the MDS algorithm, but with the Dementia Rating Scale instead of the MMSE. The original MDS procedure misclassified 11 patients (12.8%) as false negatives and 3 (3.5%) as false positives, leading to 65% sensitivity and 95% specificity. The main reason for misdiagnoses was insensitivity of the MMSE total score. Three attempts were made to reach a better screening performance, which warrants high sensitivity more than high specificity: 1. exclusion of the MMSE total score as a diagnostic requirement; 2. determination of a better cut off through Receiver Operating Characteristic curve analysis; 3. replacement of the MMSE with the equally undemanding, but more PD-specific, Mini Mental Parkinson. The first two strategies generally yielded high sensitivity, but poor specificity. The best outcome was achieved using a Mini Mental Parkinson total score <27 as cognitive criterion: sensitivity was 87% and negative predictive value was 90%; however, specificity was only 67%. Our findings seem to suggest that MDS practical guidelines are specific, but might benefit from the use of more PD-oriented tools than the MMSE in terms of sensitivity.


Subject(s)
Algorithms , Dementia/diagnosis , Neuropsychological Tests/standards , Parkinson Disease/psychology , Aged , Dementia/etiology , Female , Humans , Male , Parkinson Disease/complications , ROC Curve , Sensitivity and Specificity
6.
Funct Neurol ; 28(2): 121-5, 2013.
Article in English | MEDLINE | ID: mdl-24125562

ABSTRACT

The Scales for Outcomes in Parkinson's disease-Cognition (SCOPA-Cog) has been shown to be a clinimetrically rigorous and valid instrument for a disease-oriented neuropsychological assessment of Parkinson's disease (PD) patients. In the present study we evaluated the psychometric properties of the Italian version of the SCOPA-Cog in 121 PD patients. The scale explores memory, attention, and executive and visuospatial functions and takes approximately 20 minutes to administer. Data distribution (skewness= -0.23) and internal consistency (Cronbach's alpha= 0.78) were satisfactory. Standard error of measurement was 3.42. The outcome was significantly worse in patients with an abnormal Psychometric properties of the Italian version of the Scales for Outcomes in Parkinson's disease-Cognition (SCOPA-Cog) score on the Dementia Rating Scale (DRS) (SCOPACog mean score 14.6 ± 5.1 out of a total of 43) with respect to cognitively intact subjects (24.2 ± 4.3) (p<0.0001). The DRS showed good convergent validity (Spearman rho= 0.77, p<0.0001), and a high coefficient of variation (= 0.34). These findings support the goodness of the Italian SCOPA-Cog in terms of metrics and validity.


Subject(s)
Cognition Disorders/diagnosis , Neuropsychological Tests , Parkinson Disease/diagnosis , Aged , Aged, 80 and over , Female , Humans , Italy , Male , Middle Aged , Psychometrics
7.
Parkinsonism Relat Disord ; 19(12): 1160-3, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24011719

ABSTRACT

The detection of cognitive decline in Parkinson's disease (PD), at the Mild Cognitive Impairment (MCI) stage, has prognostic and treatment implications. The Movement Disorders Society (MDS) has recently published criteria and guidelines for the diagnosis of possible and probable PD-MCI. In the present study we assessed the ability of the Scales for Outcomes in Parkinson's disease-Cognition (SCOPA-Cog) to discriminate possible PD-MCI cases from patients with PD-dementia (PDD) and from cognitively intact PD subjects. Hundred-and-thirteen consecutive PD patients underwent the MMSE, the Dementia Rating Scale and an interview on independence in daily living, and were classified as cognitively intact (n = 49), or as possible PD-MCI (n = 33) or PDD (n = 31), according to MDS criteria. Logistic regression analysis was carried out with PD-MCI diagnosis (yes/no) as an outcome variable, and age, education and the SCOPA-Cog total score as covariates. Classification of cases according to the regression model was used for constructing Receiver Operating Characteristic (ROC) curves. Area Under the Curve (AUC) was 0.92 [95% CI 0.86-0.98], for the differential diagnosis between PD-MCI and cognitively normal patients, and 0.97 [95% CI 0.80-1.00], for the differential diagnosis between PD-MCI and PDD. Sensitivity and specificity were 90% and 73% for the PD-MCI versus no cognitive impairment differentiation, at the cutpoint ≥24, and 93% and 97% for the PD-MCI versus PDD discrimination, at the cutpoint ≥17. The SCOPA-Cog is a quick and psychometrically sound PD-specific scale. Our findings support its use for the screening of possible PD-MCI.


Subject(s)
Cognitive Dysfunction/diagnosis , Parkinson Disease/psychology , Aged , Area Under Curve , Cognitive Dysfunction/etiology , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Parkinson Disease/complications , ROC Curve
8.
J Neural Transm (Vienna) ; 120(4): 613-8, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23462799

ABSTRACT

Imaging and neuropathology studies have demonstrated significant abnormalities not only in subcortical, but also in cortical regions of patients with multiple system atrophy (MSA). This raises the possibility that cognitive dysfunction may contribute to the clinical spectrum of this disorder to a greater extent than it is currently not widely appreciated. In this cross-sectional multicenter study from the European multiple system atrophy study group ( http://www.emsa-sg.org ), we applied an extensive neuropsychological test battery in a series of 61 clinically diagnosed probable MSA patients. The results demonstrated that general cognitive decline as assessed by MMSE was uncommon (2 out of 61 patients <24). In contrast, frontal lobe-related functions (as measured by FAB) were impaired in 41 % of patients, with abstract reasoning and sustained attention less compromised. This pattern was similar to our control group of 20 patients with Parkinson's disease (matched for disease duration and age at onset). There was no difference in cognitive performance between MSA patients with the parkinsonian versus the cerebellar variant. Behaviourally, MSA patients had greater depression than PD and in the case of MSA of the cerebellar variant significantly lower anxiety. Our data show that cognitive abnormalities are relatively frequent in multiple system atrophy and this involves primarily frontal-executive functions. Their contribution to clinical disability and disease progression needs to be addressed in larger prospective studies.


Subject(s)
Attention/physiology , Cerebellum/physiopathology , Cognition/physiology , Multiple System Atrophy/psychology , Parkinsonian Disorders/psychology , Aged , Anxiety/psychology , Cross-Sectional Studies , Depression/psychology , Disease Progression , Female , Humans , Male , Middle Aged , Multiple System Atrophy/physiopathology , Neuropsychological Tests , Parkinsonian Disorders/physiopathology
9.
Neurol Sci ; 34(10): 1751-8, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23423464

ABSTRACT

The MiniMental Parkinson (MMP) has been derived from the MiniMental State Examination (MMSE) for the screening of cognitive impairment in Parkinson's disease by adding subtests that were focused on executive and visuo-spatial impairment more than on memory or language deficits. In this multicenter study, the psychometric and validity properties of the MMP have been evaluated in 69 cognitively intact and 52 cognitively impaired patients with Parkinson's disease, classified according to their performance at the Dementia Rating Scale. The MMP showed better metrics and convergent validity, and higher screening ability. However, its performance was not fully satisfying in terms of data distribution, coefficient of variation and specificity, and Receiver Operating Characteristic curves did not show clear cut superiority of either scale at their best sensitivity-specificity trade off. The MMP seems to be slightly preferable to the MMSE only at a cut off that favours sensitivity with respect to specificity, for screening purposes. The test is simple and quick, but has limitations in terms of validity.


Subject(s)
Cognition Disorders/diagnosis , Executive Function/physiology , Mental Status Schedule , Parkinson Disease/diagnosis , Perceptual Disorders/diagnosis , Space Perception/physiology , Aged , Aged, 80 and over , Analysis of Variance , Cognition Disorders/etiology , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Parkinson Disease/complications , Perceptual Disorders/etiology , Psychometrics , ROC Curve , Reproducibility of Results
10.
Nutr Metab Cardiovasc Dis ; 23(3): 264-71, 2013 Mar.
Article in English | MEDLINE | ID: mdl-21906920

ABSTRACT

BACKGROUND & AIMS: To investigate the association between anthropometric indices of body fat distribution and cardiometabolic risk factors in a population of Parkinson's disease (PD) patients. METHODS & RESULTS: One hundred and fifty-seven PD patients (57.3% males) were studied measuring: waist circumference (WC), waist-hip ratio (WHR), waist-to-height ratio (WtHR), body fat percentage (BF%) by impedance, fasting glucose, serum lipids. Information was collected also on diabetes, hypertension and metabolic syndrome (MetS). Increased cardiometabolic risk was defined by ≥2 MetS component traits other than abdominal adiposity. In the whole population, prevalence of overweight and obesity were 35.0% and 19.2%, respectively. However, prevalence of MetS and elevated cardiometabolic risk were 14.6% and 18.5%, respectively. Prevalence was similar between genders, with one exception: adverse fat distribution according to WC and WHR was more common in females (P < 0.001). Using a multivariable model (adjustments: age, smoking status and disease duration), indices were highly correlated with BF% in both genders. WC and WtHR were associated with the number of MetS criteria and elevated risk. The only cardiometabolic parameters associated with anthropometric indices were HDL in men and triglycerides in women. After adjusting also for BMI all the associations found with anthropometric indices disappeared. CONCLUSIONS: Despite their correlation with BF%, anthropometric indices of body fat distribution appear to poorly account for the reduced cardiometabolic risk of the PD patient. This finding suggests a low metabolic activity within the adipose tissue. The implications of fat distribution on the cardiometabolic risk of PD patients clearly deserves further investigation.


Subject(s)
Body Fat Distribution/adverse effects , Hypertension/epidemiology , Metabolic Syndrome/epidemiology , Obesity/epidemiology , Parkinson Disease/epidemiology , Adipose Tissue/metabolism , Adiposity , Aged , Anthropometry , Blood Glucose/analysis , Body Mass Index , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Female , Humans , Hypertension/etiology , Male , Metabolic Syndrome/complications , Middle Aged , Nutrition Assessment , Obesity/complications , Parkinson Disease/complications , Prevalence , Risk Factors , Triglycerides/blood
11.
Neurology ; 78(19): 1507-11, 2012 May 08.
Article in English | MEDLINE | ID: mdl-22539572

ABSTRACT

OBJECTIVE: Recent literature suggests that diabetes is a risk factor for Parkinson disease (PD). We investigated the clinical features of patients with idiopathic PD (IPD) in whom the onset of diabetes came first. METHODS: We designed a case-control study. From the cohort of all new patients with IPD free of vascular disease (n = 783) admitted and evaluated at our institute over a 3-year period (2007-2010), we included all the patients with a diagnosis of diabetes prior to PD onset (n = 89) and a control group (n = 89) matched (1:1) for gender, body mass index (± 1 kg/m(2)), and duration of PD (± 1 year). The Unified Parkinson's Disease Rating Scale (UPDRS) motor score was the primary endpoint. RESULTS: At study entry, patients with diabetes were similar to controls in terms of most demographic, lifestyle, and general medical features with exception of statins (18% vs 3.4%; p = 0.003). However, diabetes was associated with higher UPDRS motor (22.3 ± 9.0 vs 19.3 ± 7.9; p = 0.019) and activities of daily living (9.7 ± 5.1 vs 8.3 ± 4.3; p = 0.049) scores, more severe Hoehn & Yahr staging (p = 0.009), and higher treatment doses of levodopa (mg/day, 448 ± 265 vs 300 ± 213; p < 0.0001; mg/kg/day, 5.8 ± 4.0 vs 3.8 ± 2.9; p < 0.0001). CONCLUSIONS: Onset of diabetes before the onset of PD appears to be a risk factor for more severe PD symptoms. These findings support the hypothesis that diabetes has a role in the etiopathogenesis of PD. Neurologists should be aware of the potential impact of diabetes on overall PD management.


Subject(s)
Diabetes Mellitus, Type 2/complications , Parkinson Disease/complications , Parkinson Disease/diagnosis , Aged , Aged, 80 and over , Case-Control Studies , Diabetes Mellitus, Type 2/physiopathology , Disease Progression , Female , Humans , Male , Middle Aged , Parkinson Disease/physiopathology , Risk Factors , Severity of Illness Index
12.
Eur J Neurol ; 19(3): 468-72, 2012 Mar.
Article in English | MEDLINE | ID: mdl-21981324

ABSTRACT

BACKGROUND AND PURPOSE: Creative drive and enhanced artistic-like production may emerge in patients with Parkinson's disease (PD) during dopaminergic therapy. However, it has not been described to date whether this artistic-like production results from dopaminergic drugs triggering innate skills or it could be considered as a repeated behavior possibly associated with impulse control disorders (ICDs). METHODS: We investigated creative drive in a cohort of cognitively preserved patients with PD by means of the Torrance Test of Creative Thinking (TTCT). We also investigated a putative association between creative drive and ICDs in 36 PD patients with (PD-c) or without (PD-nc) increased artistic-like production and 36 healthy controls (HC). We considered artistic-like productivity to be enhanced if patients reported working on any form of art more than 2h per day after the introduction of dopaminergic treatment. The TTCT, the Barratt Impulsiveness Scale (BIS-11A), the Minnesota Impulsive Disorders Interview (MIDI), and the Punding Rating Scale were applied. RESULTS: Mean TTCT score of PD-c was found to be similar to HC (169.4±51.6 vs. 170.2±69.7, respectively), and both PD-c and HC had significantly higher TTCT scores than patients with PD-nc (125.4±46.1 P<0.05). TTCT did not correlate with any demographic or clinical data in both PD subgroups. No correlation was found between TTCT, BIS-11A, and MIDI. CONCLUSIONS: Our study suggests that newly acquired artistic-like production in patients with PD is not associated with impulsivity or ICDs. Artistic-like production might represent the emerging of innate skills in a subset of predisposed patients with PD on dopaminergic therapy.


Subject(s)
Antiparkinson Agents/therapeutic use , Creativity , Parkinson Disease/complications , Parkinson Disease/psychology , Disruptive, Impulse Control, and Conduct Disorders/etiology , Dopamine Agents/therapeutic use , Humans , Impulsive Behavior , Middle Aged , Parkinson Disease/drug therapy
14.
Minerva Gastroenterol Dietol ; 57(2): 117-21, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21587143

ABSTRACT

AIM: The aim of this paper was to assess the effects of milk fermented with the probiotic strain Lactobacillus casei Shirota on constipation in Parkinson's disease patients. Constipation is a common secondary symptom in patients suffering from Parkinson's Disease (PD), generally treated with dietary therapy, soluble fiber supplements and macrogol laxatives without sodium sulfate. There are no studies on the use of probiotics in the treatment of constipation in these patients. The effects of the administration of Lactobacillus casei Shirota on gastrointestinal symptoms have been assessed in two randomized controlled trials on patients suffering from chronic constipation. METHODS: Forty PD patients suffering from constipation according to Rome III criteria were recruited. We compared the characteristic of intestinal function during two periods with different treatments: in the first week the patients treated constipation only with dietetic therapy; in the following 5 weeks the patients treated constipation not only with dietetic therapy, but also taking a 65 mL fermented milk drink containing 6.5×109 CFU of Lactobacilus casei Shirota daily.They completed a daily diary for 6 weeks, recording details related to their intestinal function. RESULTS: After probiotic intake we observed a statistically significant increase in the number of days per week in which stools were of normal consistency (P<0.01) and significant reductions in the number of days per week in which patients felt bloated (P<0.01), experienced abdominal pain (P<0.01) and sensation of incomplete emptying (P<0.01). CONCLUSION: This pilot study showed that a regular intake of probiotics can significantly improve stool consistency and bowel habits in Parkinson's disease patients.


Subject(s)
Constipation/diet therapy , Lacticaseibacillus casei , Parkinson Disease/diet therapy , Probiotics/administration & dosage , Aged , Constipation/etiology , Female , Humans , Male , Parkinson Disease/complications , Pilot Projects , Treatment Outcome
15.
Eur J Neurol ; 18(1): 195-7, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20482608

ABSTRACT

BACKGROUND: Studies on familial aggregation might be of help to evaluate whether the genetic background has a key role in Progressive Supranuclar Palsy (PSP) and Corticobasal Syndrome (CBS). Only a few studies are available. OBJECTIVE: To evaluate the prevalence of positive family history (FH) in PSP and CBS in a large sample of patients. METHODS: Two hundred and thirty patients and 110 controls entered the study. Patients underwent an extensive clinical, neurological and neuropsychological assessment as well as a structural brain imaging study. A clinical follow-up further confirmed the diagnosis. Familial aggregation was carefully recorded by a standardised questionnaire. RESULTS: One hundred and twenty-nine PSP (age at onset = 66.6 +/- 7.3, female = 46.1%) and 101 CBS (age at onset = 62.8 +/- 8.9, female = 41.6%) were consecutively enrolled. Positive FH was found in 31.8% of PSP (n = 41) and in 31.7% of CBS (n = 32). Familial aggregation was lower in the age-matched control group compared to patient group (21.8%, P = 0.05). Patients with PSP had higher positive FH for Parkinsonism (63.4%) when compared to FH for dementia (36.6%). In CBS, FH was equally distributed between Parkinsonism (53.1%) and dementia (46.9%). In addition, FH was not associated with age at disease onset in PSP (FH+ versus FH-, 67.0 +/- 7.3 vs. 66.7 +/- 7.1, P = 0.788) and in CBS (62.6 +/- 7.9 vs. 62.9 +/- 9.5, P= 0.877). CONCLUSIONS: These results argue for familial aggregation in PSP and CBS, further underlying the importance of genetic background in these disorders. Further studies on possible genetic modulators or genetic epistasis contributing to PSP and CBS development are warranted.


Subject(s)
Basal Ganglia Diseases/genetics , Supranuclear Palsy, Progressive/genetics , Aged , Basal Ganglia Diseases/epidemiology , Female , Humans , Italy/epidemiology , Male , Middle Aged , Supranuclear Palsy, Progressive/epidemiology , Syndrome
16.
Neurology ; 71(1): 28-34, 2008 Jul 01.
Article in English | MEDLINE | ID: mdl-18509094

ABSTRACT

BACKGROUND: Microtubule-associated protein tau (MAPT) has been associated with several neurodegenerative disorders including forms of parkinsonism and Parkinson disease (PD). We evaluated the association of the MAPT region with PD in a large cohort of familial PD cases recruited by the GenePD Study. In addition, postmortem brain samples from patients with PD and neurologically normal controls were used to evaluate whether the expression of the 3-repeat and 4-repeat isoforms of MAPT, and neighboring genes Saitohin (STH) and KIAA1267, are altered in PD cerebellum. METHODS: Twenty-one single-nucleotide polymorphisms (SNPs) in the region of MAPT on chromosome 17q21 were genotyped in the GenePD Study. Single SNPs and haplotypes, including the H1 haplotype, were evaluated for association to PD. Relative quantification of gene expression was performed using real-time RT-PCR. RESULTS: After adjusting for multiple comparisons, SNP rs1800547 was significantly associated with PD affection. While the H1 haplotype was associated with a significantly increased risk for PD, a novel H1 subhaplotype was identified that predicted a greater increased risk for PD. The expression of 4-repeat MAPT, STH, and KIAA1267 was significantly increased in PD brains relative to controls. No difference in expression was observed for 3-repeat MAPT. CONCLUSIONS: This study supports a role for MAPT in the pathogenesis of familial and idiopathic Parkinson disease (PD). Interestingly, the results of the gene expression studies suggest that other genes in the vicinity of MAPT, specifically STH and KIAA1267, may also have a role in PD and suggest complex effects for the genes in this region on PD risk.


Subject(s)
Gene Expression/genetics , Genetic Predisposition to Disease/genetics , Genetic Variation/genetics , Parkinson Disease/genetics , tau Proteins/genetics , Aged , Brain/metabolism , Brain/pathology , Chromosomes, Human, Pair 17/genetics , Cohort Studies , DNA Mutational Analysis , DNA Repeat Expansion/genetics , Female , Genetic Testing , Genotype , Haplotypes/genetics , Humans , Male , Middle Aged , Parkinson Disease/metabolism , Parkinson Disease/pathology , Polymorphism, Single Nucleotide/genetics
17.
J Neural Transm (Vienna) ; 115(5): 721-9, 2008 May.
Article in English | MEDLINE | ID: mdl-18335163

ABSTRACT

In vitro studies revealed serotonin transporter (5-HTT) decline in Parkinson's disease (PD). Yet, few studies investigated thalamic 5-HTT in vivo and its effect on PD heterogeneity. We analyzed thalamic [(123)I]beta-CIT binding (mainly reflecting 5-HTT binding) in 32 drug-naïve PD patients and 13 controls with SPECT. Twenty-six patients were examined twice (17 months apart). Based on UPDRS scores, we identified subgroups of patients with moderate/severe tremor (PD(T)) and without tremor (PD(WT)) at the time of clinical diagnosis. Additionally, depressive symptoms were evaluated using the Beck Depression Inventory (BDI) at baseline. Mean thalamic specific to non-specific [(123)I]beta-CIT binding ratio was lower in patients when compared to controls, and further decreased during follow-up. At baseline, average thalamic ratio was significantly lower in the PD(T) than in the PD(WT) subgroup. No correlation was found between BDI scores and thalamic binding ratios. Our findings show decline of [(123)I]beta-CIT binding to thalamic 5-HTT in PD and its possible contribution to tremor onset.


Subject(s)
Cocaine/analogs & derivatives , Parkinson Disease , Radiopharmaceuticals/pharmacokinetics , Serotonin Plasma Membrane Transport Proteins/metabolism , Thalamus/diagnostic imaging , Tremor , Adult , Aged , Analysis of Variance , Cocaine/pharmacokinetics , Female , Follow-Up Studies , Humans , Male , Middle Aged , Parkinson Disease/complications , Parkinson Disease/diagnostic imaging , Parkinson Disease/pathology , Thalamus/drug effects , Tomography, Emission-Computed, Single-Photon/methods , Tremor/diagnostic imaging , Tremor/etiology , Tremor/pathology
18.
Neurodegener Dis ; 5(3-4): 244-6, 2008.
Article in English | MEDLINE | ID: mdl-18322402

ABSTRACT

BACKGROUND: A significant percentage of patients with Parkinson's disease (PD) continue to experience motor fluctuations and dyskinesias despite the association of dopamine agonists and levodopa with COMT or MAO-B inhibitors. The use of apomorphine infusion is limited by compliance while deep brain stimulation is feasible only for a small number of patients mostly because of age constraints. OBJECTIVE: To assess prospectively the effectiveness of duodenal levodopa infusion on quality of life as well as motor features in patients with advanced PD. In all but 1 case levodopa infusion was stopped at nighttime. METHODS: We report the outcome of 22 PD patients, followed for up to 2 years, who were on continuous duodenal levodopa/carbidopa infusion through percutaneous endoscopic gastrostomy. RESULTS: We found a significant reduction in 'off' period duration as well as dyskinesia severity (Unified Parkinson's Disease Rating Scale part IV, items 33 and 39). There was significant improvement in the 39-item Parkinson's Disease Quality of Life Questionnaire as well as in the Unified Parkinson's Disease Rating Scale part II up to the 2-year follow-up. Five patients withdrew: 2 for poor compliance and 3 for adverse events (1 was related to percutaneous endoscopic gastrostomy). CONCLUSIONS: These results demonstrate significant clinical improvements in quality of life and activities of daily living consistent with the occurrence of a satisfactory therapeutic response and a reduction in dyskinesia severity.


Subject(s)
Duodenum/drug effects , Levodopa/administration & dosage , Parkinson Disease/drug therapy , Parkinson Disease/psychology , Quality of Life/psychology , Disease Progression , Duodenum/physiology , Female , Humans , Infusions, Parenteral , Male , Parkinson Disease/physiopathology , Prospective Studies
19.
Eur J Neurol ; 15(1): 22-8, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18042244

ABSTRACT

Extradural motor cortex stimulation (EMCS) has been proposed as alternative to deep brain stimulation (DBS) in the treatment of Parkinson's disease (PD). Its mechanisms of action are still unclear. Neuroimaging evidenced motor cortical dysfunction in PD that can be reversed by therapy. We performed left hemisphere EMCS surgery in six advanced PD patients fulfilling CAPSIT criteria for DBS with the exception of age >70 years. After 6 months, we measured regional cerebral blood flow (rCBF) at rest with SPECT and Tc-99m cysteinate dimer bicisate off-medication with stimulator off and on. Clinical assessment included Unified Parkinson's Disease Rating Scale part II and III, Abnormal Involuntary Movement Scale and mean dopaminergic medication dosage. We used statistical parametric mapping for imaging data analysis. Clinically we observed no mean changes in motor scales, although blinded evaluation revealed some benefit in individual patients. We found significant rCBF decrements in the pre-central gyrus, pre-motor cortex and caudate nucleus bilaterally, left prefrontal areas and right thalamus. Perfusion increments were found in cerebellum bilaterally. EMCS determined significant modulation of neuronal activity within the cortico-basal ganglia-thalamo-cortical motor loop in our cohort of advanced PD patients. However, these effects were paralleled by mild and variable clinical efficacy.


Subject(s)
Electric Stimulation Therapy/methods , Motor Cortex/diagnostic imaging , Motor Cortex/physiopathology , Parkinson Disease/diagnostic imaging , Parkinson Disease/therapy , Tomography, Emission-Computed, Single-Photon/methods , Aged , Brain/anatomy & histology , Brain/diagnostic imaging , Brain/physiopathology , Cerebrovascular Circulation/physiology , Cohort Studies , Cysteine/analogs & derivatives , Electrodes, Implanted , Female , Humans , Image Processing, Computer-Assisted , Male , Neural Pathways/anatomy & histology , Neural Pathways/diagnostic imaging , Neural Pathways/physiopathology , Organotechnetium Compounds , Parkinson Disease/physiopathology , Treatment Outcome
20.
Eur J Neurol ; 14(8): 944-6, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17662021

ABSTRACT

We describe clinical and imaging features of a patient with sporadic progressive ataxia and palatal tremor (PAPT) of unknown etiology. There was hypertrophy of bilateral inferior olivary nuclei with hyperintense T2-weighted signal and mild cerebellar atrophy at brain magnetic resonance imaging. 18F-fluoro-2-desoxy-d-glucose positron emission tomography scanning (FDG-PET) showed hypometabolism in the red nucleus, external globus pallidus and precuneus while FP-CIT-SPECT imaging revealed mild and progressive loss of striatal dopaminergic terminals. Our findings suggest that in idiopathic PAPT involvement of the dentato-rubro-olivary pathway occurs along with some dopaminergic dysfunction.


Subject(s)
Basal Ganglia Diseases/physiopathology , Cerebellar Ataxia/physiopathology , Dopamine/deficiency , Myoclonic Cerebellar Dyssynergia/physiopathology , Myoclonus/physiopathology , Basal Ganglia/metabolism , Basal Ganglia/pathology , Basal Ganglia/physiopathology , Basal Ganglia Diseases/diagnostic imaging , Basal Ganglia Diseases/pathology , Cerebellar Ataxia/diagnostic imaging , Cerebellar Ataxia/pathology , Cerebellar Diseases/diagnostic imaging , Cerebellar Diseases/pathology , Cerebellar Diseases/physiopathology , Cerebellar Nuclei/metabolism , Cerebellar Nuclei/pathology , Cerebellar Nuclei/physiopathology , Diagnosis, Differential , Dopamine Plasma Membrane Transport Proteins/metabolism , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Myoclonic Cerebellar Dyssynergia/diagnostic imaging , Myoclonic Cerebellar Dyssynergia/pathology , Myoclonus/diagnostic imaging , Myoclonus/pathology , Neural Pathways/metabolism , Neural Pathways/pathology , Neural Pathways/physiopathology , Olivary Nucleus/metabolism , Olivary Nucleus/pathology , Olivary Nucleus/physiopathology , Parkinson Disease/metabolism , Parkinson Disease/pathology , Positron-Emission Tomography , Red Nucleus/metabolism , Red Nucleus/pathology , Red Nucleus/physiopathology , Tomography, Emission-Computed, Single-Photon
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