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Introduction: Abnormal oro-buccal functions including dysarthria, sialorrhea and dysphagia commonly affect patients with Parkinson's disease (PD). Objectives: To estimate the prevalence of such oro-buccal symptoms at baseline in the first 419 patients with PD included in the COPARK cohort and to analyze their correlations with patients' demographics, clinical characteristics, and drugs consumption. Methods: Patients were assessed using the Unified PD Rating Scale, the Hospital Anxiety and Depression Scale, and the PDQ-39. Dysarthria, sialorrhea, and dysphagia were defined as UPDRS items 5, 6, or 7 ≥ 1. Results: Dysarthria, sialorrhea, or dysphagia were present in 51%, 37%, or 18% out of the 419 patients, respectively. At least one of these symptom was present in 267/419 patients (65%), whilst a combination of symptoms was present in 136/419 (33%). Logistic regression showed that the presence of each of the three oro-buccal symptoms was significantly correlated with that of the two others. Other correlations included male gender, hallucinations, disease severity, levodopa use and lack of opiates consumption for dysarthria; disease severity, orthostatic hypotension and absence of antidepressants consumption for sialorrhea; female gender, motor fluctuations, and depressive symptoms for dysphagia. None of the three oro-buccal symptoms were associated with a reduced PDQ-39 score. Conclusion: Oro-buccal symptoms were present in two of three patients with moderate PD, the presence of each symptoms being significantly correlated with that of the two others. [ABSTRACT FROM AUTHOR]

Background and purpose: Pathological gambling (PG) in Parkinson’s disease (PD) is a frequent impulse control disorder associated mainly with dopamine replacement therapy. As impairments in decision-making were described independently in PG and PD, the objective of this study was to assess decision-making processes in PD patients with and without PG. Methods: Seven PD patients with PG and 13 age, sex, education and disease severity matched PD patients without gambling behavior were enrolled in the study. All patients were assessed with a comprehensive neuropsychiatric and cognitive evaluation, including tasks used to assess decision-making abilities under ambiguous or risky situations, like the Iowa Gambling Task (IGT), the Game of Dice Task and the Investment Task. Results: Compared to PD patients without gambling behavior, those with PG obtained poorer scores in the IGT and in a rating scale of social behavior, but not in other decision-making and cognitive tasks. Conclusions: Low performance in decision-making under ambiguity and abnormal social behavior distinguished PD patients with PG from those without this disorder. Dopamine replacement therapy may induce dysfunction of the ventromedial prefrontal cortex and amygdala-ventral striatum system, thus increasing the risk for developing PG. [ABSTRACT FROM AUTHOR]

Background: There is a clear need for brief, sensitive and specific cognitive screening instruments in Parkinson’s disease (PD). Objectives: To study Addenbrooke’s Cognitive Examination (ACE) validity for cognitive assessment of PD patient’s using the Mattis Dementia Rating Scale (MDRS) as reference method. A specific scale for cognitive evaluation in PD, in this instance the Scales for Outcomes of Parkinson’s disease – Cognition (SCOPA-COG), as well as a general use scale the Mini-mental state examination (MMSE) were also studied for further correlation. Methods: Forty-four PD patients were studied, of these 27 were males (61%), with a mean (SD) age of 69.5 (11.8) years, mean (SD) disease duration of 7.6 (6.4) years (range 1–25), mean (SD) total Unified Parkinson’s Disease Rating Scale (UPDRS) score 37 (24) points, UPDRS III 16.5 (11.3) points. MDRS, ACE and SCOPA-COG scales were administered in random order. All patients remained in on-state during the study. Results: Addenbrooke’s Cognitive Examination correlated with SCOPA-COG ( r = 0.93, P < 0.0001), and MDRS ( r = 0.91 P < 0.0001) and also with MMSE ( r = 0.84, P < 0.001). Area under the receiver-operating curve, taking MDRS as the reference test, was 0.97 [95% confidence interval (CI): 0.92–1.00] for ACE, 0.92 (95% CI: 0.83–1.00) for SCOPA-COG and 0.91 (95% CI: 0.83–1.00) for MMSE. Best cut-off value for ACE was 83 points [Sensitivity (Se) = 92%; Specificity (Sp) = 91%; Kappa concordance (K) = 0.79], 20 points for the SCOPA-COG (Se = 92%; Sp = 87%; K = 0.74) and 26 points for MMSE (Se = 61%; Sp = 100%; K = 0.69). Conclusion: Addenbrooke’s Cognitive Examination appears to be a valid tool for dementia evaluation in PD, with a cut-off point which should probably be set at 83 points, displaying good correlation with both the scale specifically designed for cognitive deficits in PD namely SCOPA-COG, as well as with less specific tests such as MMSE. [ABSTRACT FROM AUTHOR]

It has been suggested that potential risk of hemiballismus after subthalamotomy makes DBS preferable to ablation for IPD treatment; however, cost and the need for regular electrode control have also been observed as disadvantages to stimulation. The objective was to compare efficacy and safety of different surgical approaches to STN, in a prospective randomized pilot study. Sixteen consecutive IPD patients randomized to receive either: bilateral STN-DBS, bilateral subthalamotomy or unilateral subthalamotomy plus contralateral STN-DBS implantation, and followed for 12 months after surgery. One patient died and was excluded from the analysis. Total and motor UPDRS scores, as well as drug-induced dyskinesias improved significantly at 1 year follow-up, regardless of the procedure administered and without statistically significant differences between treatment modalities. Discrete changes were observed on ACE and MMSE scores. Psychiatric examination of patients subjected to bilateral stimulation and lesion, revealed slight increment in apathy and irritability scores, coinciding with significant deterioration of mentation, behaviour and mood as measured using the UPDRS. One patient presented persistent hemiballismus and required ulterior posteroventral pallidotomy. In this small group of patients, overall motor performance significantly improved after all three procedures, without major differences in outcome. Adverse events were, nevertheless, observed after both ablation and stimulation. The role of bilateral subthalamotomy in patients unable to receive a DBS electrode-implant merits further exploration in a larger series of patients with longer follow-up. [ABSTRACT FROM AUTHOR]

Two patients with severe Parkinson’s disease undergoing partial or complete ablative interruption of basal ganglia (BG) output are presented. One patient who underwent bilateral subthalamotomy, and a second who underwent unilateral posteroventral pallidotomy, followed 7 years later by a bilateral subthalamotomy because of contralateral disease progression, were studied. In addition to the usual clinical evaluation, changes in joint kinematics observed during unconstrained, skilled multi-joint movement and repetitive single joint (RSJ) movement of the wrist were studied. Clinical UPDRS items referred to hand movements contralateral to the procedure, and instrumental measurement of RSJ improved in both patients after either pallidotomy or subthalamotomy. When both BG outflow paths were interrupted as was the case in the second patient (bilateral subthalamotomy after the initial pallidotomy), no added clinical improvement was observed, RSJ even deteriorated slightly. Instrument-based studies for movement alteration detection after simultaneous ablation of the globus pallidus and the subthalamic nucleus of these two patients showed greater sensitivity than clinical evaluation alone. Complex gestural movement performance remained unaffected after partial (subthalamotomy or pallidotomy) or complete interruption of BG outflow (case 2), indicating BG compensatory capacity after total outflow interruption remained intact. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyse and compare published data during the last decade on the different approaches to Parkinson's disease surgery. Eighty-eight papers published between 1990 and 2001 fulfilled the inclusion criteria. Full-text and prospective papers on lesion and stimulation of GPi or STN were assessed. Descriptive analysis of surgery procedure and population under study was performed, as well as a meta-analysis of the most consistently reported variables. A total of 1702 patients underwent surgery with a mean age of 58.75 years (range 46.5 - 72.5), mean duration of illness 13.6 years (8.1 - 18.1) and a male:female ratio 1.5:1. Mean postoperative follow-up was 9 months (1 - 52). Single blind assessment was performed in two papers, while double blind evaluation was used in 6. In the GPi group, no difference was found between the pre- and postoperative levodopa equivalent daily dose (960.39 v . 943.13; p  > 0.05), while the STN group showed a marked reduction (1104.8 v . 483.04; p < 0.05) of this dosage. Meta-analysis of the most consistently reported variables (UPDRS total score, UPDRS motor score, UPDRS ADL score and Schwab & England score showed that Nucleus, Bilaterality of Approach and Surgical Procedure were the best moderators for defining outcome. Bilateral DBS STN procedures proved to be associated with better outcome. Microelectrode recording was not found to be a moderator that influenced outcome. Although there was a significant improvement of dyskinesias among the different approaches described in the papers, the heterogeneity of data makes it impossible to perform a structured analysis on this item. [ABSTRACT FROM AUTHOR]

Eight of the first 15 patients with advanced Parkinson's disease who underwent microelectrode guided posteroventral pallidotomy developed transient abnormal involuntary movements during thermolesion, four of whom also did so during high frequency macrostimulation. Abnormal involuntary movements found before thermolesion were choreic, ballistic, or choreoathetoid in nature, usually persisted less than 60 minutes, and were contralateral to the site of thermolesion in six and bilateral in two of them. The appearance of abnormal involuntary movements during macrostimulation or thermolesion of the internal globus pallidus correlated with better surgical outcome as measured by UPDRS motor items and CAPIT timed test, so that they seem to be of prognostic value. [ABSTRACT FROM AUTHOR]

Objective: To examine neuropsychological and neuropsychiatric differences between patients with probable Alzheimer's disease and patients with Parkinson's disease and dementia.Methods: Thirty three patients with probable Alzheimer's disease and 33 patients with Parkinson's disease and dementia were matched for age, sex, and mini mental state examination scores and given a battery of neuropsychological and neuropsychiatric tests.Results: Patients with Parkinson's disease with dementia had a significantly higher prevalence of major depression than patients with Alzheimer's disease; patients with Alzheimer's disease showed more severe anosognosia and disinhibition than patients with Parkinson's disease. Whereas no significant between group differences were found on tests of memory and language, demented patients with Parkinson's disease had a significantly greater impairment on a test of visual reasoning than patients with Alzheimer's disease.Conclusion: There were significant psychiatric differences between patients with Alzheimer's disease and demented patients with Parkinson's disease, but neuropsychological differences were restricted to a single cognitive domain. [ABSTRACT FROM AUTHOR]

The prevalence and clinical correlates of extrapyramidal signs in a consecutive series of 78 patients with Alzheimer's disease attending a neurology clinic, and 20 age comparable normal controls, were examined. Based on the unified Parkinson's disease rating scale (UPDRS) findings, 18 patients (23%) met criteria for parkinsonism, 44 (56%) had isolated extrapyramidal signs, and 16 (21%) had no extrapyramidal signs. Whereas the control group showed a similar prevalence of isolated extrapyramidal signs (57%), none of them showed parkinsonism. No significant differences were found for age, sex, duration of illness, and severity of dementia among the three Alzheimer's disease groups. Patients with Alzheimer's disease-parkinsonism, however, showed a significantly higher frequency of major depression and dysthymia and significantly higher Hamilton depression scores than patients with isolated or no extrapyramidal signs. Patients with Alzheimer's disease-parkinsonism also showed significantly more deficits on frontal lobe related tasks such as the Wisconsin card sorting test, trail making test, and verbal fluency, as well as on tests of constructional praxis and abstract reasoning than patients with Alzheimer's disease but no extrapyramidal signs. In conclusion, the study showed a specific association between Alzheimer's disease and parkinsonism, as well as significant relations between parkinsonism, deficits in executive functions, and depression among patients with Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Background: Dyskinesias are a transient but severe complication of subthalamotomy in some patients. Patients and methods: Three patients with Parkinson's disease undergoing bilateral micro-recording guided surgery of the subthalamic nucleus (STN) are described; deep brain stimulation (DBS) was used in one case, and subthalamotomy in the other two. Prior to surgery, levodopa induced dyskinesia had improved (⩽50%) under treatment with amantadine (400 mg/day, po) in all three patients. The patient treated with DBS developed severe dyskinesia a few days after discharge and began self medication with amantadine but showed no improvement. This suggested a possible lack of response to amantadine for treatment of dyskinesias induced by surgery of the STN. Results: Both patients treated with bilateral subthalamotomy developed unilateral choreoballistic movements immediately after surgery, despite not taking levodopa (L-dopa). Patients were scored using the dyskinesia scale and started treatment with 400 mg amantadine (po) for 4 days within the first postoperative week with no effect on dyskinesia score or its phenomenology. Amantadine was therefore discontinued. One month after surgery both patients were free of involuntary movements with an improvement of about 60% in the ‘off’ state UPDRS motor score. Six month follow up showed maintained antiparkinsonian benefit, without need for levodopa treatment and complete absence of dyskinesia. Conclusion: The present findings suggest that: (i) amantadine probably exerts its anti-dyskinetic effect by acting on the ‘indirect’ pathway; (ii) the pathophysiological mechanisms of subthalamotomy induced dyskinesias may differ from those involved in L-dopa induced dyskinesias; (iii) dyskinesias induced by STN surgery resolve spontaneously as compensatory mechanisms develop. [ABSTRACT FROM AUTHOR]

Whether there may be any relationship between stressful or traumatic life events (LE) and the subsequent motor symptoms onset in Parkinson's disease (PD) is still controversial. To explore whether a subjectively perceived as stressful or traumatic LE were more frequently present in a group of recent motor onset parkinsonian patients (Recent Onset Parkinsonism - ROP) compared with healthy controls (HC) and a group of patients already diagnosed as PD. A consecutive series of 139 ROP patients, 138 matched PD patients and 138 HC were pooled through a validated LE exposure questionnaire evaluating the number of patients affected by LE and the amount of LE per group occurred in the last year, segregating by subjective severity in total and severe LE. There was no significant difference in the percentage of patients affected by total (p = 0.134) nor by severe (p = 0.133) LE within the 3 groups. No significant difference was observed in the number of total LE between ROP and HC (p = 0.063), ROP and PD (p = 0.688), nor in severe LE (ROP vs. HC, p = 0.637. ROP vs. PD, p = 0.500). During the year of parkinsonian motor symptoms onset, the number of ROP patients exposed to total or severe LE or the amount of total or severe LE suffered by ROP were not significantly different to the group of PD patients or HC. A casual relationship between LE and the onset of motor symptoms in parkinsonian patients may be suggested. • Whether Parkinson's disease (PD) manifests initial motor symptoms or these are recognized after life events (LE) is unresolved. • The number of recent onset parkinsonism (ROP) patients exposed to LE was not different to PD patients or Healthy Controls (HC). • The number of LE per group was not different between ROP and PD nor ROP and HC, beyond their severity. • Our results suggest a random relationship between the onset of motor parkinsonian symptoms and exposure to LE. [ABSTRACT FROM AUTHOR]

Objective: To determine whether brain white matter hyperintensities (WMH) influence l-dopa response in Parkinson's disease (PD) patients. Methods: We prospectively evaluated 60 PD patients with an acute l-dopa challenge test, and assessed motor performance with the Movement Disorders Society revised Unified Parkinson's Disease Rating Scale (MDS-UPDRS) during "ON" and "OFF" medication states. Magnetic resonance images were examined using a visual semi-quantitative rating scale for quantification and distribution analysis of WMH. l-dopa challenge test response was correlated to extent and location of WMH, to determine a potential association between them. Results: Subjects with greater deep WMH burden, showed less response to l-dopa on axial motor symptoms (R = -0.35; p < 0.027), when tested with Part III of the MDS-UPDRS before and after acute levodopa challenge. Conclusions: Results suggest WMH may affect response to l-dopa on axial function of PD patients, which could be due to either non-dopaminergic (cortico-basal ganglia) motor pathway disruption, or postsynaptic nigrostriatal pathway involvement. [ABSTRACT FROM AUTHOR]

Parkinson's disease is marked by neurodegenerative processes that affect the pattern of discharge of basal ganglia neurons. The main features observed in the parkinsonian globus pallidus pars interna (GPi), a subdomain of the basal ganglia that is involved in the regulation of voluntary movement, are pathologically increased and synchronized neuronal activity. How these changes affect the implemented neuronal code is not well understood. Our experimental temporal structure-function analysis shows that in parkinsonian animals the rate-coding window of GPi neurons needed for the proper performance of voluntary actions is reduced. The model of the GPi network that we develop and discuss here reveals indeed that the size of the rate-coding window shrinks as the network activity increases and is expanded if the coupling strength among the neurons is increased. This leads to the novel interpretation that the pathological neuronal synchronization in Parkinson's disease in the GPi is the result of a collective attempt to counterbalance the shrinking of the rate-coding window due to increased activity in GPi neurons. [ABSTRACT FROM AUTHOR]