Clinical correlates of serum 25-hydroxyvitamin D in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) patients have lower levels of serum 25-hydroxyvitamin D (25(OH)D) than the general population. Previous studies have suggested a negative association between 25(OH)D and clinical features of PD, but the data are inconsistent. MATERIALS AND METHODS: We conducted a cross-sectional, observational study. Serum 25(OH)D, disease (Hoehn-Yahr stage [HY]) and clinical symptom (Unified Parkinson Disease Rating Scale [UPDRS]) severity and global cognitive functions (Mini-Mental State Examination [MMSE]) were studied in 500 consecutive PD patients not using vitamin D supplements. Information on sunlight exposure and dietary intakes (using a 66-item food frequency questionnaire) were also collected. A convenient sample of age and sex-matched community healthy controls (N = 100) was included as a control group. RESULTS: PD patients had lower 25(OH)D serum levels than controls. Deficiency status (<20 ng/mL) was found in 65.6% of patients. 25(OH)D levels were independently correlated to sunlight exposure (P = .002) and vitamin D intake (P = .009). In multivariate models, using a Mendelian randomization approach, lower serum 25(OH)D was associated with more severe disease (HY, P = .035), worse clinical symptoms (UPDRS Part-III total score [P = .006] and dopaminergic [P = .033] and non-dopaminergic subscores [P = .001]) and greater global cognitive function impairment (P = .041). Neither cognitive functions nor clinical features were associated with reduced intake of vitamin D and sunlight exposure. CONCLUSION: : Serum 25(OH)D was negatively correlated with disease and symptoms severity, as well as with global cognitive functions. Our study adds to the evidence that low 25(OH)D may affect the progression of PD negatively. Intervention studies in this area are required.

The VDR FokI (rs2228570) polymorphism is involved in Parkinson's disease.

The etiology of Parkinson's disease (PD) is presumably multifactorial and likely involves interactions between genetic and environmental factors, as well as mitochondrial dysfunction, oxidative stress and inflammation. Among environmental factors, Vitamin D was reported to associate with the risk of PD. Vitamin D activity is mediated by its binding to the vitamin D Receptor (VDR), a transcriptional factor for almost 3% of human genes. We genotyped for ApaI, BsmI, TaqI, FokI and rs1989969 VDR single nucleotide polymorphisms (SNPs) a cohort of 406 PD and 800 healthy controls (HC) and found a strong association between the FokI (rs2228570) VDR SNP and PD. Thus, the TT genotype and the T allele resulted associated with PD in the overall analyzed PD population. Gender-based stratification of data indicated that results were maintained for FokI TT genotype and T allele in male PD patients, whereas the FokI T allele alone was confirmed as a risk factor for PD in females. Co-segregation analyses indicated the TaqI ApaI FokI rs1989969 GCTG as a "risk" haplotype for PD. In a subgroup of patients and controls neural Vitamin D and VDR concentration was analyzed in extravesicles (NDEVs) isolated from peripheral blood: no differences emerged between PD and HC. NDEVs results will need to be validated in ampler cohort but we can speculate that, if at neuronal level the amounts of Vitamin D and of VDR are comparable, than the bioavailability of vitamin D and the efficacy of the vitamin D/VDR axis is differentially modulated in PD by VDR SNPs.

Selegiline reduces daytime sleepiness in patients with Parkinson's disease.

OBJECTIVES: Excessive daytime sleepiness (EDS) affects a large percentage of Parkinson's disease (PD) patients, and it is enhanced by dopamine agonist drugs. Currently, there is no treatment of choice for EDS in PD. Our aim was to check the clinical impression that some patients who were given selegiline, a selective inhibitor of monoamine oxidase B, experienced an improvement in their daytime somnolence. METHODS: In the present study, we retrospectively identified 45 Parkinson's disease patients (21 females and 24 males) among those referred to the PD Center in Varese that (a) showed excessive daytime sleepiness, usually developed after the introduction of a dopamine agonist, (b) were given selegiline 10 mg to improve their treatment schedule independently of excessive sleepiness, and (c) in whom the Epworth Sleepiness Scale (ESS) and the Parkinson's Disease Sleep Scale (PDSS) scores were available both before and 3 months after the introduction of selegiline. RESULTS: We compared the corresponding scores (ESS, PDSS, and UPDRS III) evaluated before and 3 months after the introduction of selegiline by the nonparametric Mann-Whitney U test: The differences showed a statistically significant improvement of somnolence but no change in the UPDRS III scores. CONCLUSION: Despite some limitations, our data suggest that selegiline may be a valuable add-on therapy in PD patients to reduce their daytime somnolence.

Effectiveness of expiratory flow acceleration in patients with Parkinson's disease and swallowing deficiency: A preliminary study.

OBJECTIVES: Parkinson's disease (PD) causes dysfunction both to swallowing and to the cough mechanism. Oropharyngeal dysphagia is the main cause of pneumonia, due to silent aspiration of food and saliva. Pneumonia is the leading cause of death in PD. Different strategies exist to reduce the risk of inhalation and associated lung infections, but evidence of their efficacy is still unclear. The aim of this preliminary study was to investigate if adding an expiratory flow acceleration (EFA®) technique to standard therapy (ST) for dysphagia can reduce the incidence of bronchopulmonary infections and improve quality of life, respiratory function parameters, cough, and airways encumbrance perception. MATERIALS AND METHODS: Twenty-five patients with PD were randomized to two groups: ST vs. ST + EFA. Patients were re-assessed at 30, 180 and 360 days from start of treatment. The primary outcome was the incidence of respiratory exacerbations together with quality of life score (PDQ-39). Secondary outcomes were changes in respiratory function tests, cough capacity (CPEF), perceived health status (Euro-QOL-VAS), cough, and upper airways encumbrance perception evaluated by visual numeric scale (VNS). RESULTS: Twenty patients concluded the study (10 each group). Albeit the difference was not significant, less respiratory infections, symptoms, hospital admissions and medical visits were found in the study group. Furthermore, there was a significant difference in cough effectiveness measured with the peak cough expiratory flow (PCEF) and other spirometry parameters (FEV1, FVC), and also in specific and generic health-related quality of life measures (PDQ-39, Euro-QoL-VAS). CONCLUSION: The results of this preliminary study support the use of EFA® technology in Parkinson's patients with dysphagia to reduce the risk of respiratory complications. Nevertheless, further studies are needed in a larger, more representative sample to definitively confirm the usefulness of this technique in PD patients.

Design and Operation of the Lombardy Parkinson's Disease Network.

Background: Parkinson's disease (PD) is one of the most common chronic neurological conditions leading to disability and social burden. According to the 2016 Italian National Plan on Chronic Diseases, regional health authorities are implementing dedicated networks to manage neurological diseases, including PD. Methods: A panel of experts representing health-care providers in Lombardy reached consensus on the organization of a patient-centered regional PD healthcare network. Results: The panel proposed a structure and organization implementing a hub-and-spoke PD network model. Three levels of neurological services were identified: General Neurologist, PD Clinic, PD Center. This model was applied to health service providers currently accredited in Lombardy, yielding 12 candidate PD Centers, each serving an area of ~1,000-2,000 km2, and not less than 27 PD Clinics. The panel agreed on uniform diagnostic and staging criteria for PD, and on a minimum common clinical data set, on PD patient management by the network at initial and follow-up assessments, on the cadence of follow-up visits, on patient referrals, and on outcome measures for the assessment of network activities. Conclusions: The implementation of disease-centered networks for chronic neurological diseases provides an innovative opportunity to improve patient management, facilitate research and education.

The TANDEM investigation: efficacy and tolerability of levodopa-carbidopa intestinal gel in (LCIG) advanced Parkinson's disease patients.

The TANDEM investigation was carried out in 17 Italian Movement Disorder centers on behalf of a joint initiative of neurologist members of the Italian Academy for Parkinson's disease and Movement Disorders (LIMPE-DISMOV Academy) and gastroenterologist members of the Italian Society of Digestive Endoscopy (SIED) to evaluate the efficacy and tolerability of levodopa-carbidopa intestinal gel (LCIG) in patients with advanced Parkinson's disease (PD) in routine medical care. Motor scores in "ON" and OFF" state (UPDRS-III), complications of therapy (UPDRS-IV), activities of daily living, sleep disorders and quality of life were evaluated at baseline and at two follow-up assessments (FUV1 and FUV2) within the initial 12-month LCIG treatment. In 159 patients (55% males) with a mean age of 69.1 ± 6.6 years and a diagnosis of PD since 13.6 ± 5.5 years, the UPDRS-III total score (in "OFF") decreased from baseline (45.8 ± 13.2) to FUV1 (41.0 ± 17.4; p < 0.001) and FUV2 (40.5 ± 15.5; p < 0.001), the UPDRS-IV total score decreased from baseline (8.8 ± 2.9) to FUV1 (5.1 ± 3.4; p < 0.001) and FUV2 (5.5 ± 3.2; p < 0.001). The percentage of patients exhibiting freezing, dystonia, gait/walking disturbances, falls, pain and sleep disorders was significantly reduced. Twenty-eight device complications were reported and 11 (6.9%) patients prematurely terminated the study. LCIG after 12-month treatment led to sustained improvement of time spent in "OFF", complications of therapy, PD-associated symptoms and sleep disorders. LCIG tolerability was consistent with the established safety profile of LCIG.

Muscle-targeted nutritional support for rehabilitation in patients with parkinsonian syndrome.

OBJECTIVE: We evaluated the efficacy of muscle-targeted nutritional support on the functional outcomes of multidisciplinary intensive rehabilitation treatment (MIRT) in patients with Parkinson disease (PD) or parkinsonism. METHODS: We conducted a pragmatic, bicentric, randomized (1:1), assessor-blind controlled trial (Protein, Leucine and Vitamin D Enhancing Rehabilitation [PRO-LEADER]; April 2017 to January 2018) in cognitively intact patients with PD or parkinsonism and undergoing a 30-day MIRT. Patients (n = 150) received a standard hospital diet with or without a whey protein-based nutritional supplement enriched with leucine and vitamin D twice daily. The primary efficacy endpoint was the increase in the distance walked during a 6-minute walking test (6MWT). Secondary endpoints were changes in 4-meter walking speed, Timed Up and Go test (TUG), Berg balance scale, handgrip strength, Self-assessment Parkinson's Disease Disability Scale, body weight, and skeletal muscle mass (SMM). RESULTS: Nutritional support resulted in greater increase in the distance walked during 6MWT (mean 69.6 meters [95% confidence interval (CI) 60.7-78.6]) than no support (51.8 meters [95% CI 37.0-66.7]): center-adjusted mean difference, 18.1 meters (95% CI 0.9-35.3) (p = 0.039). Further adjustment for changes in dopaminergic therapy and SMM yielded consistent results: mean difference, 18.0 meters (95% CI 0.7-35.2) (p = 0.043). A meaningful effect was also found for the following secondary endpoints: 4-meter walking speed (p = 0.032), TUG (p = 0.046), SMM, and SMM index (p = 0.029). Six patients discontinued the nutritional therapy due to mild side effects. CONCLUSION: The consumption of a whey protein-based nutritional formula enriched with leucine and vitamin D with MIRT improved lower extremity function and preserved muscle mass in patients with PD or parkinsonism.Clinicaltrials.gov IDENTIFIER: NCT03124277. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients with parkinsonism undergoing intensive rehabilitation, a whey protein-based nutritional formula enriched with leucine and vitamin D increased distance walked on the 6MWT.

SNAP25 Gene Polymorphisms Protect Against Parkinson's Disease and Modulate Disease Severity in Patients.

Parkinson's disease (PD) is a α-synucleinopathy in which intracellular aggregates of α-synuclein (α-syn) result in neurodegeneration and in the impairment of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex-mediated release of neurotransmitters. SNAP25 is a SNARE complex component: its concentration is increased in the cerebrospinal fluid of PD patients and this is related to the severity of cognitive and motor symptoms. Five SNAP25 single-nucleotide polymorphisms (SNPs) that modulate gene expression and were described to play a role in neurologic conditions (rs363050, rs363039, rs363043, rs3746544, and rs1051312) were analyzed in a cohort of 412 sporadic Italian PD patients and 1103 healthy controls (HC) in order to identify possible correlation with the disease. The SNAP25 rs1051312 C allele and CC genotype confer protection against PD onset, in particular in males (p = 0.003, OR(95%CI) = 0.67(0.51-0.88)) (pc = 0.008, OR(95%CI) = 0.28(0.10-0.70)). Co-segregation analyses revealed that the rs1051312 effect was reinforced when present within the rs363043 C-rs3746544 T-rs1051312 C haplotype (p = 3.3 × 10-4, OR = 0.47, 95%CI = 0.31-0.72), once again in males. Finally, rs363039 influenced age at onset (p = 0.02) and MMSE (Mini-Mental State Examination) scores (p = 0.01). The SNAP25 SNPs analyzed herein modulate gene expression at different levels as they are involved in binding miRNA and transcription factors; this suggests a possible synergistic effect of SNAP25 SNPs in the pathogenesis of PD. A replication in a larger and independent sample will help to further explore this hypothesis.

Correction to: Efficacy of safinamide on non-motor symptoms in a cohort of patients affected by idiopathic Parkinson's disease.

The original version of this article contains an error in Table 2. The Authors realized that they submitted the previous version of Table 2. The correct version of Table 2 is shown here.

Efficacy of safinamide on non-motor symptoms in a cohort of patients affected by idiopathic Parkinson's disease.

The primary endpoint of this work was to evaluate the effect of safinamide on non-motor symptoms (NMS) in patients affected by idiopathic Parkinson's disease (PD) complicated by motor fluctuations. We retrospectively collected data from 20 subjects affected by idiopathic PD in treatment with L-dopa alone or in combination with dopamine agonists, who began to be treated with safinamide due to the occurrence of motor fluctuations. Secondary endpoints included SCales for Outcomes in Parkinson's disease (SCOPA) Motor Scale, cognitive assessment, the Hoehn and Yahr stage, Clinical Impression of Severity Index for Parkinson's Disease, Hospital Anxiety And Depression Scale, Physical and Mental Fatigue, Parkinson's disease Sleep Scale, Parkinson's Disease Questionnaire-8 (PDQ-8) and EQ-5D. Each one of these scales/questionnaires was performed at baseline and T1. For efficacy analyses, continuous variables were treated with descriptive statistics, using mean and standard deviations. A non-parametric test (the Friedman test) was carried out to evaluate the statistical significance of the results observed. We found a statistically significant reduction of the total score of NMS, of 6 domains out of 9, and 13 items out of 30. A statistically significant reduction of SCOPA Motor Scale, PDQ-8, and CISI was also detected. In conclusion, our data showed a positive effect of safinamide on NMS and confirm its positive effect on motor symptomatology.

Parkinson's disease patients have a complex phenotypic and functional Th1 bias: cross-sectional studies of CD4+ Th1/Th2/T17 and Treg in drug-naïve and drug-treated patients.

BACKGROUND: Parkinson's disease (PD) affects an estimated 7 to 10 million people worldwide, and only symptomatic treatments are presently available to relieve the consequences of brain dopaminergic neurons loss. Neuronal degeneration in PD is the consequence of neuroinflammation in turn influenced by peripheral adaptive immunity, with CD4+ T lymphocytes playing a key role. CD4+ T cells may however acquire proinflammatory phenotypes, such as T helper (Th) 1 and Th17, as well as anti-inflammatory phenotypes, such as Th2 and the T regulatory (Treg) one, and to what extent the different CD4+ T cell subsets are imbalanced and their functions dysregulated in PD remains largely an unresolved issue. METHODS: We performed two cross-sectional studies in antiparkinson drug-treated and drug-naïve PD patients, and in age- and sex-matched healthy subjects. In the first one, we examined circulating Th1, Th2, Th17, and in the second one circulating Treg. Number and frequency of CD4+ T cell subsets in peripheral blood were assessed by flow cytometry and their functions were studied in ex vivo assays. In both studies, complete clinical assessment, blood count and lineage-specific transcription factors mRNA levels in CD4+ T cells were independently assessed and thereafter compared for their consistency. RESULTS: PD patients have reduced circulating CD4+ T lymphocytes, due to reduced Th2, Th17, and Treg. Naïve CD4+ T cells from peripheral blood of PD patients preferentially differentiate towards the Th1 lineage. Production of interferon-γ and tumor necrosis factor-α by CD4+ T cells from PD patients is increased and maintained in the presence of homologous Treg. This Th1-biased immune signature occurs in both drug-naïve patients and in patients on dopaminergic drugs, suggesting that current antiparkinson drugs do not affect peripheral adaptive immunity. CONCLUSIONS: The complex phenotypic and functional profile of CD4+ T cell subsets in PD patients strengthen the evidence that peripheral adaptive immunity is involved in PD, and represents a target for the preclinical and clinical assessment of novel immunomodulating therapeutics.

The Length of SNCA Rep1 Microsatellite May Influence Cognitive Evolution in Parkinson's Disease.

BACKGROUND: Alpha-synuclein is a constituent of Lewy bodies and mutations of its gene cause familial Parkinson's disease (PD). A previous study showed that a variant of the alpha-synuclein gene (SNCA), namely the 263 bp allele of Rep1 was associated with faster motor progression in PD. On the contrary, a recent report failed to detect a detrimental effect of Rep1 263 on both motor and cognitive outcomes in PD. Aim of this study was to evaluate the influence of the Rep1 variants on disease progression in PD patients. METHODS: We recruited and genotyped for SNCA Rep1 426 PD patients with age at onset ≥40 years and disease duration ≥4 years. We then analyzed frequency and time of occurrence of wearing-off, dyskinesia, freezing of gait, visual hallucinations, and dementia using a multivariate Cox's proportional hazards regression model. RESULTS: SNCA Rep1 263 carriers showed significantly increased risk of both dementia (HR = 3.03) and visual hallucinations (HR = 2.69) compared to 263 non-carriers. Risk of motor complications did not differ in the two groups. CONCLUSION: SNCA Rep1 263 allele is associated with a worse cognitive outcome in PD.

TNF-α -308 G/A and -238 G/A promoter polymorphisms and sporadic Parkinson's disease in an Italian cohort.

The etiology of sporadic Parkinson's disease is (PD) still not understood but it is believed that a complex interplay between environmental and genetic factors could trigger the pathology. Pro-inflammatory TNF-α is released by activated microglia and is up-regulated in the brain and cerebrospinal fluid of PD patients; TNF-α modulates neuroinflammation and can activate the molecular mechanisms that lead to neurotoxicity and neuronal death. We analyzed two functional SNPs within the TNF-α gene promoter (rs361525 and rs1800629) in 354 Italian PD patients and 443 healthy controls (HC). In our cohort of patients, no significant associations could be observed between rs361525 and rs1800629 SNPs and either PD onset risk or PD-associated clinical parameters including age at onset of fluctuations, UPDRS-ME (Unified Parkinson Disease Rating Scale-Motor Examination), Schwab & England, Hohen & Yahr stage scale, and MMSE (Mini-Mental State Examination) score. Conflicting results on the role played by TNF-α rs1800629 SNP on PD onset risk are present in the literature. We could not find any association between TNF-α rs361525 and rs1800629 and PD.

Polymorphisms of Dopamine Receptor Genes and Risk of L-Dopa-Induced Dyskinesia in Parkinson's Disease.

L-dopa-induced dyskinesia (LID) is a frequent motor complication of Parkinson's disease (PD), associated with a negative prognosis. Previous studies showed an association between dopamine receptor (DR) gene (DR) variants and LID, the results of which have not been confirmed. The present study is aimed to determine whether genetic differences of DR are associated with LID in a small but well-characterized cohort of PD patients. To this end we enrolled 100 PD subjects, 50 with and 50 without LID, matched for age, gender, disease duration and dopaminergic medication in a case-control study. We conducted polymerase chain reaction for single nucleotide polymorphisms (SNP) in both D1-like (DRD1A48G; DRD1C62T and DRD5T798C) and D2-like DR (DRD2G2137A, DRD2C957T, DRD3G25A, DRD3G712C, DRD4C616G and DRD4nR VNTR 48bp) analyzed genomic DNA. Our results showed that PD patients carrying allele A at DRD3G3127A had an increased risk of LID (OR 4.9; 95% CI 1.7-13.9; p = 0.004). The present findings may provide valuable information for personalizing pharmacological therapy in PD patients.

Dopaminergic Receptors on CD4+ T Naive and Memory Lymphocytes Correlate with Motor Impairment in Patients with Parkinson's Disease.

Parkinson's disease (PD) is characterized by loss of dopaminergic neurons in substantia nigra pars compacta, α-synuclein (α-syn)-rich intraneuronal inclusions (Lewy bodies), and microglial activation. Emerging evidence suggests that CD4+ T lymphocytes contribute to neuroinflammation in PD. Since the mainstay of PD treatment is dopaminergic substitution therapy and dopamine is an established transmitter connecting nervous and immune systems, we examined CD4+ T naive and memory lymphocytes in PD patients and in healthy subjects (HS), with specific regard to dopaminergic receptor (DR) expression. In addition, the in vitro effects of α-syn were assessed on CD4+ T naive and memory cells. Results showed extensive association between DR expression in T lymphocytes and motor dysfunction, as assessed by UPDRS Part III score. In total and CD4+ T naive cells expression of D1-like DR decrease, while in T memory cells D2-like DR increase with increasing score. In vitro, α-syn increased CD4+ T memory cells, possibly to a different extent in PD patients and in HS, and affected DR expression with cell subset-specific patterns. The present results support the involvement of peripheral adaptive immunity in PD, and may contribute to develop novel immunotherapies for PD, as well as to better use of current dopaminergic antiparkinson drugs.

Intensive rehabilitation treatment in early Parkinson's disease: a randomized pilot study with a 2-year follow-up.

BACKGROUND: Although physical exercise improves motor aspects of Parkinson's disease (PD), it is not clear whether it may also have a neuroprotective effect. Objective. In this 2-year follow-up study, we determined whether intensive exercise in the early stages of the disease slows down PD progression. METHODS: Forty newly diagnosed patients with PD were treated with rasagiline and randomly assigned to 2 groups: MIRT Group (two 28-day multidisciplinary intensive rehabilitation treatments [MIRT], at 1-year interval) and Control Group (only drug). In both groups, Unified Parkinson's Disease Rating Scale Section II (UPDRS II), UPDRS III, 6-minute walking test (6MWT), Timed Up-and-Go test (TUG); PD Disability Scale (PDDS), and l-dopa equivalents were assessed at baseline (T0), 6 months (T1), 1 year (T2), 18 months (T3), and 2 years (T4) later. RESULTS: Over 2 years, UPDRS II, UPDRS III, TUG, and PDDS differentially progressed in the 2 groups: In the MIRT Group, all scores at T4 were better than at T0 (all Ps < .03). No changes were noted in the Control Group. l-dopa equivalent dosages increased significantly only in the Control Group (P = .0015), with a decrease in the percentages of patients in monotherapy (T1 40%; T2, T3, and T4 20%). In the MIRT Group, the percentages of such patients remained higher (T1 and T2 100%; T3 89%; T4 75%). CONCLUSIONS: These results suggest that MIRT might slow down the progression of motor decay, it might delay the need for increasing drug treatment, and thus, it might have a neuroprotective effect.

Multidisciplinary intensive rehabilitation treatment improves sleep quality in Parkinson's disease.

BACKGROUND: Sleep disturbances are among the most common non-motor symptoms of Parkinson's disease (PD), greatly interfering with daily activities and diminishing life quality. Pharmacological treatments have not been satisfactory because of side effects and interactions with anti-parkinsonian drugs. While studies have shown that regular exercise improves sleep quality in normal aging, there is no definitive evidence in PD. METHODS: In a retrospective study, we determined whether an intense physical and multidisciplinary exercise program improves sleep quality in a large group of patients with PD. We analyzed the scores of PD Sleep Scale (PDSS), which was administered twice, 28 days apart, to two groups of patients with PD of comparable age, gender, disease duration and pharmacological treatment. The control group (49 patients) did not receive rehabilitation, The treated group (89 patients) underwent a 28-day multidisciplinary intensive rehabilitation program (three one-hour daily sessions comprising cardiovascular warm-up, relaxation, muscle-stretching, balance and gait training, occupational therapy to improve daily living activities). RESULTS: At enrolment, control and treated groups had similar UPDRS and PDSS scores. At re-test, 28 days later, UPDRS and total PDSS scores improved in the treated (p < 0.0001) but not in the control group. In particular, the treated group showed significant improvement in PDSS scores for sleep quality, motor symptoms and daytime somnolence. The control group did not show improvement for any item. CONCLUSIONS: These results suggest that multidisciplinary intensive rehabilitation treatment may have a positive impact on many aspects of sleep in PD.

Intensive rehabilitation increases BDNF serum levels in parkinsonian patients: a randomized study.

BACKGROUND: Exercise may decrease the risk of Parkinson's disease (PD) in humans and reduce PD symptoms in animal models. The beneficial effects have been linked to increased levels of neurotrophic factors. OBJECTIVE: We examined whether intensive rehabilitation treatment reduces motor disability in patients in the early stages of PD and increases brain-derived neurotrophic factor (BDNF) serum levels. METHODS: Thirty participants in the early stages of PD treated with rasagiline were randomly assigned to 3 hours of rehabilitation treatment that included aerobic exercise for 28 days (Group 1) or to not therapy (control; Group 2). BDNF serum levels were assessed at time T0 (baseline, before treatment), T1 (10 days), T2 (20 days), and T3 (28 days). At T0 and T3, we assessed the Unified Parkinson's Disease Rating Scale (UPDRS) III in both groups, as well as the UPDRS II and total, Berg Balance Scale, and 6-minute walking test only in Group 1. RESULTS: BDNF levels significantly increased at T1 in Group 1, an increase that was maintained throughout the treatment period. At T3 compared to T0, UPDRS III scores significantly improved in Group 1 along with scores for UPDRS II, total, Berg Balance Scale, and 6-minute walking test. CONCLUSIONS: Intensive rehabilitation treatment increases the BDNF levels and improves PD signs in patients in the early stages of the disease. These results are in line with studies on animal models of PD and healthy subjects.

Rehabilitation improves dyskinesias in Parkinsonian patients: a pilot study comparing two different rehabilitative treatments.

GOAL AND OBJECTIVES: The present study was devised: (a) to test whether an intensive (60 hours in 4 weeks) multidisciplinary rehabilitation treatment (involving physiotherapy, exercises to improve gait and balance using treadmill and stabilometric platform, occupational therapy) for Parkinsonian patients is effective in improving dyskinesia and motor performance compared to a control group undergoing a non-intensive non multidisciplinary rehabilitation treatment (30 hours in 4 weeks involving physiotherapy only); and (b) to verify whether rehabilitation may lead to a reduction in levodopa dosage. MATERIAL AND METHODS: Forty Parkinsonian patients suffering from dyskinesias were admitted to study: 20 for an intensive multidisciplinary (Group1) and 20 for a non-intensive non multidisciplinary rehabilitation treatment (Group2). The rating scales used for the clinical evaluation were: Unified Parkinson's Disease Rating Scales (UPDRS) II, III, IV, Parkinson's disease disability scale (PDDS), Abnormal Involuntary Movement Scale (AIMS). RESULTS: All outcome measurements improved in both groups of patients, but patients Group1 presented better results: UPDRS II was reduced by 33% in Group1 and by 22% in Group2, UPDRS III 29% vs. 22%, UPDRS IV 74% vs. 10%, PDDS 18% vs. 12%, and AIMS 71% vs. 8%. A different behaviour was observed for levodopa dosage at baseline and after treatment: dosage decreased by an average value of 210 mg (p< 0.0001) in Group1 and was virtually unchanged (30 mg reduction, p=0.08) in Group2. CONCLUSION: Our findings suggest that a rehabilitation protocol should be considered as a valid non-invasive therapeutic support for patients who show dyskinesias and that there are better results when the treatment is intensive.