Background: The interindividual variability in motor response to DAergic drugs is a critical factor conditioning the long-term outcome of PD patients. This is particularly relevant for DA receptor agonists, which are commnonly prescribed as initial treatment in early PD. As yet, the genetic determinants of the response to ropinirole have not been investigated in PD patients.

The aim of the study was to determine the clinical frequency and features of REM sleep behaviour disorder (RBD) in a large population of Parkinson's disease (PD) patients using defined diagnostic criteria both for RBD and PD. Six trained neurologists used a semistructured questionnaire based on ICSD-R diagnostic criteria for RBD to evaluate 200 PD patients and their caregivers. Interobserver reliability for the diagnosis of RBD was "substantial" (Kappa 0.65). Five patients were excluded from the study because of an MMSE lower than 25. The demographic and PD clinical features were compared in the clinically defined RBD group and in those without RBD (NRBD). Then the RBD features during the last year were analysed in the affected group. Out of 195 patients, 66 fulfilled the ICSD-R criteria for RBD; 62 patients reported RBD during the last year (frequency 31.8%). RBD features: two or more episodes per week in 35.5%; upper limb movements in 87%; lower limb movements in 79%; vocalisations during events in 85%. RBD onset was before PD in 27% of patients; 69% of the RBD group had injured themselves or their caregivers during sleep. According to multivariate analysis, RBD was associated with male gender, age and PD duration. Brief training and the use of a semistructured questionnaire may help the neurologist in dealing with sleep disturbances in PD patients. The search for RBD symptoms in PD is highly recommended, especially in patients with a long disease duration, the risk of sleep-related injuries being high.

The present study aimed to determine whether the bradykinesia of Parkinson's disease (PD) patients during the execution of reaching-grasping movements (i) is related to an impaired implementation of movement parameters and (ii) selectively involves the control of reach and/or grasp movements. We compared the kinematics of reaching to grasp of differently sized objects placed at different positions, among PD patients in the early stage of disease (ESPD), in the advanced stage of disease (ASPD) without L-dopa medication (off-state), and in healthy controls. In addition, we analysed the effects of L-dopa replacement therapy by comparing the kinematics of the patients in the advanced stage of disease after L-dopa administration with those of the other groups. Bradykinesia increased with disease progression, but only in the initial phases of the reach and grasp components. However at both stages of the disease, the kinematics of reaching and grasping responded to extrinsic and intrinsic object properties just as in controls. L-dopa administration improved the performance of PD patients, though this was more evident for the reach than for the grasp. We suggest that the basal ganglia (BG) are involved in implementing kinematic parameters, but neither (or only marginally) in the initial movement parameterization itself, nor in the on-line control of movement. Specifically, the BG dysfunction in PD induces a slowed implementation of movement parameters. The lack of effect of L-dopa administration on grasp kinematics may be because the motor control of distal effectors is less represented in the motor circuitry formed by the supplementary motor area (SMA), thalamus and BG.

We estimated the interobserver reliability (IR) of the diagnosis of rapid eye movement (REM) Sleep Behaviour Disorder (RBD) among trained neurologists, with the application of International Classification of Sleep Disorders Revised (ICSD-R), by means of videotaped interviews of people with motor sleep behaviour disorders of different nature. IR of clinical judgement for the diagnosis of RBD was "substantial" (Kappa 0.65); nevertheless, some criteria ('limb or body movement associated with dream mentation', criterion B, and 'sleep behaviours (that) disrupt sleep continuity', criterion C3) showed a 'moderate' IR, resulting from the intrinsic limitations of the patient report and terminological ambiguity. Further clarification of terminology of the ICSD-R criteria would be useful to improve the reliability.

. The accuracy of the clinical diagnosis of dementia with Lewy bodies (DLB) remains poor, especially in early phases of the disease, in spite of applying current consensus diagnostic criteria. The need for supportive diagnostic tools is therefore warranted. In this study EEG recordings showed a main pattern of bilateral frontal intermittent rhythmic delta activity (FIRDA) in 7 of 10 patients, aged 58–83 years, 8 of whom were diagnosed as affected by “probable” and 2 by “possible” DLB. Conversely, the same EEG abnormality was found only in 2 of 9 age-matched patients, 8 of whom had “probable” and 1 “possible” Alzheimer's disease, according to NINCDS-ADRDA criteria, taken as controls. The degree of cognitive impairment was comparable among the two groups of patients. If these findings will be confirmed in a larger series, FIRDA, even though an aspecific EEG pattern, could be of value in improving the diagnostic accuracy of DLB.

Following a two-months of placebo-controlled withdrawal, the MAO-B inhibitor selegiline was found to maintain a long term significant mild to moderate symptomatic effect on bradykinesia and tremor at rest in nine patients with Parkinson's disease (stage II and III of H&Y), whose functional impairment had also required a dopaminergic therapy with low-dose bromocriptine. Both motor signs found worsened during the wash-out showed a full recovery to pre-withdrawal condition within two months after reinstitution of the drug.

Neuroimaging studies of the striatal dopamine transporter (DAT) are useful in the assessment of the dopaminergic system in Parkinson's disease (PD). We used positron emisson tomography (PET) and the tracer [11-C]FE-CIT to measure DAT binding in the caudate nucleus and putamen of 31 patients with PD, 5 with essential tremor and 8 healthy control subjects. Of the patients with PD, 17 were drug naive, while the others were either on levodopa or dopamine agonist monotherapy. DAT binding was significantly reduced in the caudate nucleus and to a greater extent in the putamen of PD patients compared to both healthy controls and essential tremor individuals. No overlap was observed between putamen values in PD and normals. No differences were found between controls and essential tremor subjects. These data confirm that measurements of DAT binding can provide an accurate and highly sensitive measure of degeneration in the dopamine system in PD.

The kinematics of the action formed by reaching–grasping an object and placing it on a second target was studied in a patient who suffered from an acute vascular left brain lesion, which affected the Supplementary Motor Area proper (SMA-proper) (Matelli M, Luppino G. Thalamic input to mesial and superior area 6 in the macaque monkey. Journal of Comparative Neurology 1996;372:59–87, Matelli M, Luppino G, Fogassi L, Rizzolatti G. Thalamic input to inferior area 6 and area 4 in the macaque monkey. Journal of Comparative Neurology 1989;280:468–488), and in five healthy control subjects. The reach kinematics of the controls was affected by the positions of both the reaching–grasping and the placing targets (Gentilucci M, Negrotti A, Gangitano M. Planning an action. Experimental Brain Research 1997;115:116–28). In contrast, the reach kinematics of the patient was affected only by the position of the reaching–grasping target. By comparing these results with those previously found in Parkinson’s disease patients executing the same action (Gentilucci M, Negrotti A. Planning and executing an action in Parkinson’s disease patients. Movement Disorders 1999;1:69–79, Gentilucci M, Negrotti A. The control of an action in Parkinson’s disease. Experimental Brain Research 1999;129:269–277), we suggest that the anatomical “motor” circuit formed by SMA-proper (see above), Basal Ganglia (BG) and Thalamus (Alexander GE, Crutcher MD. Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends in the Neurosciences 1990;13:266–271, Hoover JE, Strick PL. Multiple output channels in the basal ganglia. Nature 1993;259:819–821) may be involved in the control of actions: SMA-proper assembles the sequence of the action, whereas BG updates its parameters and stores them.

We evaluated the possible impairment in planning and executing an action in patients with Parkinson's disease (PD). The action considered in the present study was formed by two successive motor acts: reaching-grasping an object (first target) and placing it on a second target of the same shape and size. We examined the effects of extrinsic properties of the second target (that is, distance) on the various kinematic phases of reaching-grasping movements. Distance, position, and size of both stimuli were randomly varied across the experimental session. Movements were executed with and without visual control of both targets and arm. The performance of six patients with PD was compared with an age-matched control group. The kinematics of the initial phase of reaching was influenced by position and size of the first target and by distance of the second target in both patients and control subjects. In particular, peak acceleration was higher for farther position of the second target. However, in the subsequent phase patients, differently from control subjects, removed the effects of the second target distance by modifying their reaching kinematics. This was obtained by varying the duration of the acceleration phase. In summary, the patients reprogrammed the reaching component by taking into account only the properties of the first target. The decreasing influence of second-target distance on reaching kinematics of patients was more evident during movements executed under visual control. Moreover, their movements executed without visual control were slowed down from the beginning. The second target affected the grasping kinematics only of the control subjects. Globally, these results indicate that PD patients are able to compute the general program of an action that takes into account extrinsic properties of the final target. However, the finding that PD patients reprogrammed the movement during its execution suggests a decay of the program during its time course, that is, basal ganglia can be involved in storing the plan of an action and in controlling its correct execution.

We studied, in Parkinson's disease (PD) patients and healthy control subjects, the kinematics of the action formed by two successive motor acts: reaching-grasping an object (first target) and placing it on a second target. We examined the effects of extrinsic (i.e., distance) and intrinsic (i.e., size) properties of the second target on the various kinematic phases of reaching-grasping. We randomly varied distance and size of both stimuli across the experimental session. The kinematics of the reach initial phase of both patients and controls was influenced by the distance of both the first and the second target. In particular, peak acceleration increased for farther position of the second target. However, in the subsequent phase, patients, differently from controls, modified their reaching kinematics, removing the effects of second target position. These results were due neither to a visual interference effect of the second target on reaching-grasping nor to the complexity of movement sequence. Finally, the size of the second target did not affect grasp kinematics of both patients and controls. The results of the present study support the hypothesis that PD patients are able to compute the general program of an action in which extrinsic properties of both the actual and the final target are computed. However, PD patients re-program movement during its execution. This suggests a decay of the motor program. That is, basal ganglia can be involved in storing the plan of an action and in controlling its correct execution.

We report a family affected by autosomal dominant ataxia, in which numerous members also showed microcytosis. Genetic analysis demonstrated a CAG expansion in the SCA1 locus in five members, while all subjects with microcytosis revealed a C-T substitution at codon 39 of the beta-globin gene. A pure cerebellar syndrome with prominent gait ataxia characterized the first stages of the neurological disease. The fully developed disease included additional clinical findings such as dysarthria and dysphagia, and instrumental signs of axonal involvement of the peripheral nerves. Ophthalmoplegia was not observed. The coexistence of hereditary spinocerebellar degeneration and erythropathies or hemoglobinopathies has been previously described. We discuss the possible linkages between these two pathologies.

Several environmental risk factors and some allelic variants of polymorphic drug-metabolising enzymes have been associated with sporadic Parkinson's disease. No study has to date explored the possible interaction between individual susceptibility and exposure to chemical pollutants.

A questionnaire-based case-control study was carried out on 86 patients with neurologist-confirmed idiopathic Parkinson's disease (PD) and 86 controls similar in sex and age. The control group was recruited in outpatient specialist centers of the same University Hospital (glaucoma, psoriasis vulgaris, essential arterial hypertension and renal diseases). Exposure was defined as occupational or residential contact with a given factor for at least 10 consecutive years prior to the onset of PD. Smoking habits were defined by exclusion of those subjects who never smoked. The following risk factors were identified: cranial trauma (OR: 2.88; 95% CI: 0.98-8.49), well water use (OR: 2.78; 95% CI: 1.46-5.28) and occupational exposure to industrial chemicals (OR: 2.13; 95% CI: 1.16-3.91). Among industrial chemicals, only organic solvents were identified as significant risk factors for PD (O.R. : 2.78, 95% C.I. : 1.23-6.26). Whereas no exposure to neurotoxic metals occurred among controls, making the assessment of the O.R. impossible, exposure pesticides and herbicides was similar in the two groups (O.R. : 1.15; 95% C. : 0.56-2-36). Smoking habits was negatively associated with PD (OR: 0.41; 95% CI: 0.22-0.75), confirming the "protective" role of tobacco smoking suggested by many studies. As a whole, these results support the role of environmental factors in the etiology of PD.