Progression of sleep disturbances in Parkinson’s disease: a 5-year longitudinal study

Journal of Neurology - Sleep disorders can occur in early Parkinson’s disease (PD). However, the relationship between different sleep disturbances and their longitudinal evolution has not...     

Switch from selegiline to rasagiline is beneficial in patients with Parkinson’s disease

The objective of this study is to demonstrate that application of rasagiline instead of selegiline with concomitant determination of l-amphetamine and l-methamphetamine in plasma is safe and well tolerated and influences sleep, mood, and motor behavior in patients with Parkinson’s disease on a stable drug therapy. 30 patients, who took 7.5 mg selegiline daily for at least 3 months, were switched to 1 mg rasagiline. Then they were followed over an interval of 4 months. The remaining drug therapy remained stable. This changeover was safe and well tolerated. l-Amphetamine and l-methamphetamine only appeared during selegiline treatment. Motor behavior, motor complications, mood and sleep improved during rasagiline administration. Amphetamine-like derivatives of selegiline could contribute to sleep disturbances, which may be involved in worsening of mood. Motor behavior and motor complications probably became better due to the additional glutamate receptor antagonizing properties of rasagiline in this open label study.     

Long-term duodenal levodopa infusion in Parkinson’s disease: a 3-year motor and cognitive follow-up study

Duodenal infusion of levodopa/carbidopa gel (Duodopa) is an effective treatment option for advanced Parkinson’s disease (PD). Long-term clinical experience up to 16 years suggests that the safety of this procedure is acceptable, while several observational studies showed that Duodopa reduces motor fluctuations and dyskinesias improving patients’ quality of life (QoL). The aim of this study is to investigate the long-term motor and cognitive outcome of Duodopa treatment in advanced PD patients and its’ impact on the QoL. Twenty-five consecutive PD patients were assessed using the Unified PD rating scale (UPDRS), a battery of neuropsychological tests, and the PD questionnaire (PDQ-39) at baseline and after a mean period of three years of Duodopa treatment. Seventeen out of 25 patients reached the follow-up evaluation; five patients discontinued Duodopa and three patients died of causes unrelated to drug infusion. Duodopa improved motor complications (UPDRS-IV) and quality of life (PDQ-39). A sub-group of subjects (41 %) developed a significant deterioration of cognitive functions over time. The most common adverse events were dislocation and the kinking of the intestinal tube. In conclusion, Duodopa therapy is effective in the long-term treatment of advanced PD patients. Continuous enteral levodopa infusion achieves a reduction of motor fluctuations and dyskinesias improving patients’ QoL, despite the progression of PD motor symptoms and a significant decline in cognitive functions in a sub-group of patients.     

Rapid onset of efficacy of rasagiline in early Parkinson’s disease

Rasagiline is a monoamine oxidase type-B inhibitor used as monotherapy or in addition to levodopa in the treatment of Parkinson’s disease (PD). This naturalistic single-blind study was aimed at evaluating the rapidity of onset effect of rasagiline on motor symptoms in a cohort of early relatively elderly PD patients. 102 outpatients (55 males, median age 71 years) have been selected: 26 were PD therapy-naive and 76 received rasagiline as add-on therapy. The third section of the Unified Parkinson’s Disease Rating Scale (UPDRSIII) and the Hoehn–Yahr (HY) scale were assessed at baseline and after 1 and 4 weeks thereafter. The mean UPDRS III total score (?6.7 at week 1 and ?8.9 at week 4) and single items, as well as mean HY score (?0.40 at week 1 and ?0.67 at week 4), significantly decreased from baseline (p < 0.001). Improvements were significant in both therapy-naive and add-on therapy patients: the mean decreases from baseline to week 4 in UPDRSIII and HY score were ?8.8 and ?0.46, and ?9.0 and ?0.74, respectively, in the two subgroups. The mean decrease from baseline in UPDRSIII and HY score did not significantly differ in patients aged > or ≤71 years. Rasagiline had a rapid therapeutic effect from the first week of therapy, which further improved at 4 weeks. The rapid onset of action and the absence of a dose titration are important issues in the management of the PD patient.     

Familial aggregation in atypical Parkinson’s disease: a case control study in multiple system atrophy and progressive supranuclear palsy

Familial aggregation has been consistently found in PD, but it is unclear whether there is a familial aggregation in families of patients with multiple system atrophy (MSA) or progressive supranuclear palsy (PSP). MSA and PSP cases were recruited from a two-arm case control study. One control was matched to each case for age, gender and living area. Medical history of first-degree relatives was obtained through a face-to-face questionnaire. Age-specific cumulative incidence of Parkinsonism and dementia in first-degree relatives of cases and controls was compared for MSA and PSP separately. Seventy-one pairs for MSA and their controls and 79 pairs for PSP and their controls were included. No significant familial aggregation was found in PSP. MSA cases reported Parkinsonism more often, but not dementia in their first-degree relatives than controls. MSA patients, but not those with PSP, have Parkinsonism more often in their first-degree relatives than controls.     

Comorbid disorders and hospitalisation in Parkinson’s disease: a prospective study

Abstract. Parkinsons disease (PD) is often associated with other disorders, typical of the disease or of the age of PD patients, that can lead to hospitalisation, sometimes as emergencies. In this one-year prospective, longitudinal study, we investigated the comorbid events prompting the hospitalisation, or occurring during the planned hospitalisation, of an unselected group of 180 PD patients, admitted to 9 general hospitals in the course of the study. The most frequent acute comorbid events were trauma (30.5%), mostly due to falls, and vascular disorders (29.3%). Comorbidities were closely related to PD in 50% of cases. More than 50% of patients did not require (in addition to PD therapy) specific treatment for the acute comorbid event. Older age was associated with increased risk of complications. The setting up of multidisciplinary networks covering entire territories could help to improve the way in which we tackle the clinical and social problems generated by PD and its comorbidities. *Members of the Parkinsons Disease Comorbidity Study Group D. Porazzi, F. Reverberi, Department of Neurology, Hospital of Busto Arsizio; G. Chiodelli, G. Guarneri, Department of Neurology, Hospital of Cremona; M. B. Zappacosta, Department of Neurology, Hospital of Gallarate; G. Mariani, R. Freschi, Department of Neurology, Hospital of Legnano; F. Sasanelli, G. Molini, Department of Neurology, Hospital of Melegnano; F. Schieroni, M. Di Costanzo, Department of Neurology, Hospital of Merate; G. Bargnani, E. Donati, Department of Neurology, Hospital of Rovato; G. Bono, Department of Neurology, Hospital of Varese; E. Magrotti, Department of Neurology, Hospital of Voghera.     

Case–control study of blink rate in Parkinson’s disease under different conditions

Standard neurology texts list a reduced blink rate as one of the clinical features of Parkinson's disease. However, there are few clinical studies which have quantified this clinical sign. Here we present the results of a quantified study in a cohort of cases and controls using a standard protocol. Cases meeting standard criteria for a diagnosis of Parkinson's disease were studied together with age- and sex-matched controls. Baseline data included age, sex, duration of disease, Hoehn and Yahr stage, mini-mental state examination and treatment. Subjects were videoed undertaking three different tasks: being interviewed, watching a video, and reading from a book. Blink rates were calculated as a mean 'per minute' figure for each of the three tasks. A meta-analysis of previous studies of blink rate was undertaken. A total of 20 cases and 41 controls were studied. A decline in blink rate with increasing age was seen for cases but not controls. A significant reduction in blink rate was seen in cases when compared with controls for each of the test conditions. Blink rates were highest in subjects when being interviewed and were lowest whilst reading a passage in both cases and controls. No effect of disease duration, severity or treatment was observed. We have quantified the reduction in blink rate which has long been recognised as a feature of Parkinson's disease. We have identified factors which determine blink rate within individuals. We have also been able to define normal and abnormal levels for blink rate which may be of value clinically and for future research.     

Sleep attacks in Parkinson’s disease: a clinical and polysomnographic study

Abstract. The objective of the study was to evaluate daytime sleepiness, (the features of episodes of sudden sleep onset), i. e., so-called sleep attacks (SAs), in three male Parkinsons disease (PD) patients (mean age 66 years) on chronic therapy with ropirinole or pramipexole. A structured clinical interview, the Epworth Sleepiness Scale, and continuous 24-h ambulatory polysomnography were used to assess the features of SAs occurring in the patients in their normal home environments. The polysomnographic patterns characterizing SAs (sleep occurring against a background of wakefulness, and not preceded by a feeling of sleepiness or by other heralding symptoms) were analyzed. The results showed that SAs can be clearly documented through polysomnographic monitoring and really, but rarely, occur in PD. SAs seem to represent the extreme of the continuum of daytime sleepiness observed in PD patients.     

Dynamics of impulsive–compulsive behaviors in early Parkinson’s disease: a prospective study

Journal of Neurology - Impulsive compulsive behaviors (ICBs) in Parkinson’s disease (PD) are debilitating disorders of repetitive, excessive, and compulsive nature affecting up to one third...     

Efficacy of budipine and placebo in untreated patients with Parkinson’s disease

Summary. Previous studies demonstrated the efficacy of budipine on motor symptoms of treated patients with Parkinson’s disease (PD) with rating scales. However rating procedures may be subjective and variable. Therefore additional use of instrumental motor tests are helpful to reflect therapeutic benefits. Objective was to test the efficacy of 20 mg budipine (t.i.d.) in 51 previously untreated idiopathic PD patients in a monocenter, double-blind, placebo-controlled trial with a 2:1 randomisation over a three month interval. Budipine was not superior to placebo application. However a detailed analysis of rating results shows, that budipine but not placebo treated patients significantly improved. Budipine caused significant better outcomes of motor tests with execution of complex movements, but did not change results of tasks, which demand for simple motions. Placebo significantly improved dopamine sensitive motor test results. These outcomes may result from improved non dopaminergic neurotransmission due to budipine. Placebo caused better results of dopamine sensitive tests, since placebo may release endogenous dopamine.     

Non-motor symptoms in Huntington’s disease: a comparative study with Parkinson’s disease

Journal of Neurology - The presence of non-motor symptoms in Huntington’s disease (HD) has not been systematically assessed so far. Our objective was to know their prevalence and to compare...     

Genetics of impulse control disorders in Parkinson’s disease

Impulse control disorders (ICD) have been recognised in Parkinson’s disease (PD) as adverse effects of dopamine replacement therapy, particularly with dopamine agonists. Although virtually all PD patients are treated with dopaminergic drugs, only a minority will develop hyperdopaminergic states, suggesting predisposing and/or protecting factors. The age at onset, the sex and the dose or type of dopaminergic drugs have been identified as clinical predictive factors. Recent genetic studies have investigated associations between ICD and polymorphisms of genes involved in the dopamine metabolism pathway (COMT, DAT), dopamine receptors (DRD1, DRD2, DRD3, DRD4), serotonin receptors and its transporter (HTR2A, 5HTT), and glutamate receptors (GRIN2B). Although validation in larger and independent cohorts is needed, the results from these studies give us some insights into the pathophysiology of hyperdopaminergic states and may be useful, at term, in personalising antiparkinsonian treatment in clinical practice.     

Hallucinations in Parkinson’s disease: cross-sectional study

The aim of this study was to estimate the prevalence and risk factors for the development of hallucinations in patients with Parkinson's disease (PD). This cross-sectional study included 180 consecutive, non-demented patients with PD. Out of them, 24 patients (13%) experienced some kind of hallucinations. Visual hallucinations were present in 22/24 (90%) subjects. Univariate logistic regression analysis has shown relationship between presence of hallucinations and the following variables: age of patients (p?=?0.025), PD duration (p?=?0.001), duration of levodopa treatment (p?=?0.001), total daily dose of levodopa (p?=?0.033), presence of levodopa-induced dyskinesia (p?=?0.002) and their duration (p?=?0.021), and experience of nightmares (p?=?0.042). Hallucinations were also associated with higher scores of the UPDRS (p?=?0.001), HDRS (p?=?0.001) and the NPI total score (p?=?0.001), and higher H-Y stages of the disease (p?=?0.001). Multivariate regression analysis has demonstrated that the duration of PD (p?=?0.024) as well as NPI total score (p?=?0.002) was significant independent risk factors for hallucinations in PD.     

A case control study on bone mineral density in Chinese patients with Parkinson’s disease

Although previous studies showed that patients with Parkinson’s disease (PD) have low bone mineral density (BMD), there is little data on factors predisposing PD patients to low BMD. We compared the BMD of 108 PD patients (58 females) with an average age of 68 (range 42–83) years with that of 216 sex- and age-matched controls, adjusting for other covariate factors (exercise levels, estrogen status, dietary calcium intake, smoking, drinking, body mass index, and percentage of body fat). The mean BMD in the hip and lumbar spine of male PD patients did not differ significantly from those of male controls. On the other hand, the mean BMD in femoral neck was significantly lower in female PD patients than in controls (0.53 ± 0.11 g/cm² versus 0.58 ± 0.10 g/cm², P = 0.005). Compared with controls, female PD patients experienced menopause much earlier (47 years versus 50 years, P = 0.028). The percentage of body fat was also lower in female PD patients (33% versus 36%, P = 0.02). A lower BMD in the hip in female PD patients was associated with an increased number of months after menopause (P = 0.004) and lower percentage of body fat (P = 0.025). We concluded that female patients with PD have lower hip BMD, but this association appears largely attributable to differences in percentage body fat and years since menopause. After multivariate adjustment, PD no longer remained independently associated with reduced BMD in female patients.     

Efficacy of dance for Parkinson’s disease: a pooled analysis of 372 patients

Journal of Neurology - Parkinson’s disease (PD) is a neurodegenerative disorder that presents with motor and nonmotor symptoms such as bradykinesia, resting tremor, postural instability, and...     

Gait dysfunction in Parkinson’s disease and normal pressure hydrocephalus: a comparative study

Our objectives were to characterize gait dysfunction in Parkinson’s disease (PD) and normal pressure hydrocephalus (NPH) patients, in a comparative analysis. We used a walking test to determine gait velocity (GV), stride length (SL), stride cadence and the presence of frontal (FG) and sub-cortical hypokinetic gait (SHG) features. Equilibrium was tested with the shoulder tug test (STT). These variables were used in cluster analysis, to classify subjects according to gait dysfunction. PD patients were assessed with the Unified Parkinson’s Disease Rating Scale (UPDRS) and Hoehn and Yahr (HY) scale. NPH patients were reassessed after high volume lumbar puncture (LP). NPH (n = 35) and PD (n = 40) patients had lower SL, GV and STT scores than controls (n = 30). NPH patients had worse results in SL, GV and STT than PD and a higher frequency of both FG and SHG features, compared to PD and the control groups. We found a severe/moderate gait dysfunction cluster, formed by 33 NPH patients and 11 PD patients, and a normal/mild dysfunction cluster, comprising 2 NPH, 29 PD patients and all control subjects. PD patients in the first cluster had worse UPDRS (except for tremor) and HY scores. In NPH patients, all gait variables improved after LP, although not to the controls level. PD and NPH gait was similarly characterized by loss of balance, slowness and small steps, although NPH patients performed worse. In PD patients, gait dysfunction comparable to that of NPH patients was associated with worse motor stage and the akinetic-rigid variant.     

Rehabilitation of hypomimia in Parkinson’s disease: a feasibility study of two different approaches

Parkinson’s disease (PD) patients frequently have an impairment of facial expression both in voluntary and spontaneous emotional expression. Aim of this study was to evaluate the feasibility of a rehabilitation program for hypomimia in patients with PD, comparing two different approaches. Thirty-six patients with PD were included: 20 patients received a rehabilitative intervention for hypomimia either with a DVD showing exercises focused on facial muscles (PD-group-A) or with a therapist-guided facial rehabilitation with a proprioceptive/recognition approach (PD-group-B). Sixteen patients (PD-Ctrl group) did not receive any treatment and served as control group. The feasibility of the proposed rehabilitation techniques was the main focus of this evaluation. We also evaluate the efficacy of the treatments by means of the sub-item 19 of the Unified Parkinson’s disease Rating Scale motor score (UPDRS-III) and by a computerized analysis of facial expression (E-Motion), which was assessed prior to (T0) and after therapy (T1). The proposed rehabilitative program for the treatment of hypomimia was shown to be feasible. Our data show a significant improvement in UPDRS-III sub-item 19 in PD-group-B compared to PD-group-A, (p = 0.005) and to PD-Ctrl (p = 0.003) and in expressivity of fear in PD-group-B compared to PD-Ctrl (p = 0.01). The proposed rehabilitative program showed to be feasible. A larger multi-center trial is now warranted to establish its efficacy to improve facial expression over long time period.