Progression of motor symptoms in Parkinson’s disease

Parkinson’s disease(PD)is a chronic progressive neurodegenerative disease that is clinically manifested by a triad of cardinal motor symptoms-rigidity,bradykinesia and tremor-due to loss of dopaminergic neurons.The motor symptoms of PD become progressively worse as the disease advances.PD is also a heterogeneous disease since rigidity and bradykinesia are the major complaints in some patients whereas tremor is predominant in others.In recent years,many studies have investigated the progression of the hallmark symptoms over time,and the cardinal motor symptoms have different rates of progression,with the disease usually progressing faster in patients with rigidity and bradykinesia than in those with predominant tremor.The current treatment regime of dopamine-replacement therapy improves motor symptoms and alleviates disability.Increasing the dosage of dopaminergic medication is commonly used to combat the worsening symptoms.However,the drug-induced involuntary body movements and motor complications can significantly contribute to overall disability.Further,none of the currently-available therapies can slow or halt the disease progression.Significant research efforts have been directed towards developing neuroprotective or disease-modifying agents that are intended to slow the progression.In this article,the most recent clinical studies investigating disease progression and current progress on the development of disease-modifying drug trials are reviewed.     

Computerized assessment of goal-directed behavior in Parkinson’s disease

Introduction: Apathy is a syndrome characterized by a reduction in goal-directed behavior. Neurodegenerative diseases frequently exhibit apathy. However, we lack an objective measure of apathy. The Philadelphia Apathy Computerized Task (PACT) measures impairments in goal-directed behavior that contribute to apathy, including initiation, planning, and motivation. We sought to examine these mechanisms in Parkinson’s disease (PD) patients. Method: PD patients and healthy controls with a caregiver were recruited for the study. Participants were administered the PACT, a novel computerized assessment of goal-directed behavior based on reaction times, and the Starkstein Apathy Scale (AS). Care partners completed the Neuropsychiatric Inventory (NPI). Baseline demographic characteristics of PD and control participants were compared using t tests and Wilcoxon rank sum tests. Linear regressions were used to compare PD patients to controls on each of the three PACT subtasks (initiation, planning, and motivation) while controlling for motor slowing. We then compared performance on each PACT subtask between PD subjects defined as apathetic using the NPI and Starkstein Apathy Scale and controls. Results: We included 30 PD and 15 control participants in the analysis. When controlling for motor slowing, both all PD and PD apathetic subjects were significantly slower than controls on the planning task and on the initiation task. There were no significant differences between PD patients and controls on the motivation tasks. Conclusions: PD patients showed specific initiation and planning deficits compared to control participants. After using traditional scales to define apathy, PD apathetic patients still exhibited impaired initiation and planning behaviors. These results suggest that the PACT measures aspects of impaired goal-directed behavior that may contribute to apathy in PD.     

Progression of small vessel disease correlates with cortical thinning in Parkinson’s disease

ObjectiveCerebral small-vessel disease (SVD) is a risk factor for dementia in Parkinson’s disease (PD), however the pathophysiological role of SVD in PD-dementia is unclear. We investigated the impact of baseline and progression of SVD on cortical thickness and the correlation to cognition.MethodsSeventy-three mild PD patients with baseline and follow-up structural MRI scans, serial clinical and neuropsychological assessments were studied. SVD included the load of white matter hyperintensities (WMH), lacunes and perivascular spaces (PVS). WMH progression was assessed using the modified Rotterdam Progression scale, while for lacunes and PVS, development of new lesions was considered as lesion progression. Patients were classified as having SVD-progression and SVD-no-progression based on the longitudinal changes in their SVD measures. Freesurfer was used to measure baseline and follow-up regional cortical thickness and subcortical volumes and correlated to cognitive performance.ResultsFourteen patients were classified as SVD-progression and 59 as SVD-no-progression. Over 18 months, PD SVD-progression demonstrated significant cortical thinning in the left frontal and bilateral parietal regions with associated decline in memory, executive function, and motor functions. PD SVD-progression also had reduced volumes in the nucleus accumbens and amygdala at baseline and greater atrophy in the caudate nucleus over 18 months.DiscussionThe extent and progression of SVD is associated with focal cerebral atrophy and domain-specific cognitive dysfunction. Measures to retard SVD may be potentially useful in preventing dementia in PD.     

Olfaction in Parkinson’s disease: methods of assessment and clinical relevance

Several neurological conditions have been reported to be associated with peripheral or central deficits of olfactory system. In recent years particular emphasis has been placed on the early and severe olfactory impairment in Parkinson’s disease (PD), in which limited neuropathological studies have revealed a marked dopaminergic deficit in the olfactory tubercles. Moreover, indirect evidence suggests that dysfunction of the dopaminergic pathways from mesencephalon to the piriform cortex may play a role in olfactory impairment in PD. A large number of clinical studies have reported that olfactory loss in idiopathic PD is bilateral, present in hemiparkinsonism, unrelated to the stage or clinical subtype of the disease, and independent of antiparkinsonian medication. In addition, major olfactory alterations have been reported in familial PD and dementia with Lewy bodies but not in progressive supranuclear palsy and essential tremor. These findings might stimulate further research targeted to determine the biological substrate of dissimilar olfactory performances in these movement disorders. The present review summarizes standardized procedures for the assessment of olfactory acuity (detection threshold), identification (multiple choice odor naming), discrimination (differentiation between similar/dissimilar odorants), and memory (recognition of a substance previously smelled). Specific suggestions concerning the psychometric and neuropsychological evaluation of PD patients are provided. Received: 17 April 1999/Received in revised form: /29 September 1999/Accepted: 1 October 1999     

Instruments for holistic assessment of Parkinson’s disease

Assessment of Parkinson’s disease is a complex matter as a consequence of the variety of manifestations and complications that can be present in a patient. Although a really holistic assessment is probably a utopia, a comprehensive evaluation is possible using a combination of measures completed by health professionals, patients and/or caregivers. In PD, main domains requiring assessment include motor impairment, motor complications, non-motor symptoms, disability, and patient-reported outcomes. Such scales like the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale and the battery of Scales for Outcomes in Parkinson’s disease (SCOPA) provide a wide information on the most relevant aspects of the disease. Hoehn and Yahr staging, global impression, and quality of life measures furnish summarized whole evaluations and comprehensive non-motor symptom assessments help to identify and evaluate this kind of manifestations. This article shows a pragmatic review of common instruments (rating scales and questionnaires) usable for a comprehensive assessment of PD and provides information about sources for guiding the selection of measures and outcome analyses.     

Axial perturbations evoke increased postural reflexes in Parkinson’s disease with postural instability

ObjectiveTo measure axially-evoked postural reflexes in 11 Parkinson’s disease (PD) subjects, both stable and unstable, and to compare these with 13 age-matched controls. Methods: We measured the short-latency electromyography (EMG) reflex effects of brief impulsive displacements applied to the upper sternum or C7 for tibialis anterior (TA) and soleus. Our subjects were studied standing normally and when leaning both forwards and backwards.ResultsThe initial mechanical effects of the stimuli were similar but the reflex responses for the unstable PD group were increased, even after allowing for the increased levels of tonic activation. For TA, unstable PD subjects had significantly larger responses than the stable PD group whose responses were in turn significantly larger than controls. For soleus, unstable PD subjects had significantly greater responses than controls.ConclusionsThese findings are consistent with previous evidence that exaggerated postural responses are characteristic of unstable PD subjects.SignificanceIncreased postural reflexes are characteristic of unstable PD subjects and may contribute to the instability seen for these patients in response to larger perturbations.     

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...     

Fatigue assessment of Parkinson’s disease patient in clinic: specific versus holistic

Fatigue is a frequently encountered non-motor symptom in Parkinson’s disease (PD). Being a subjective definition, with no biological markers, it is difficult to describe. Its definition is influenced by the background and culture of the patient. Subtypes of fatigue are peripheral fatigue and mental fatigue. The co-existence of other non-motor symptoms in PD complicates its assessment. Fatigue could be present before, at the time of diagnosis of PD in untreated patients or during the course of the disease. Scales that can be used for evaluation include generic one for a holistic manner and those specifically designed for PD. A scale designed for fatigue should differentiate between PD patients with fatigue and those without fatigue. The next step is to choose between unidimensional which evaluate one dimension and multidimensional scales. We present the main scales which can be used for fatigue assessment and their properties. The scales are presented with some psychometric properties in non-PD population and those properties through validation in PD population. Scales have some properties which could be recommended for screening and/or rating of severity of fatigue in PD.     

Impact of infection on risk of Parkinson’s disease: a quantitative assessment of case-control and cohort studies

Journal of NeuroVirology - Identifying modifiable risk factors for Parkinson’s disease (PD) to help prevent this disease has attracted increasing interest in recent years for the limited...     

Skin biopsy for assessment of autonomic denervation in Parkinson’s disease

Summary. Autonomic dysfunction in Parkinson’s disease (PD) is considered a late complication of the disease or an adverse effect of anti-parkinsonian medications. Morphological changes are demonstrated only by postmortem examination. The study objective was to evaluate peripheral autonomic neural involvement in PD using punch skin biopsy. The study sample included 22 patients (mean age 50 ± 7.7 years, mean disease duration 5.3 ± 3.8 years) and 19 controls. Four-millimeter skin biopsies were immunohistochemically stained with anti-PGP 9.5 antibody. Autonomic innervation of the blood vessels, sweat glands, and erector pili muscles was assessed and rated from 0 (normal) to 2 (severe). Cutaneous autonomic innervation was decreased in patients compared to controls. Semi quantitative analysis demonstrated reduced autonomic innervation of the blood vessels (1.0 ± 0.8 vs. 0.42 ± 0.8 in controls; p < 0.02), of sweat glands (0.95 ± 0.67 vs. 0.47 ± 0.61; p < 0.02) and of the erector pili muscles (1.06 ± 0.55 vs 0.21 ± 0.42; p < 0.001). This method demonstrates that the peripheral autonomic system is affected in PD at early stage of the disease and that autonomic involvement in PD may be more prevalent than previously thought. R. Dabby and R. Djaldetti contributed equally to this work     

Imaging and genetics in Parkinson’s disease: assessment of the GBA1 mutation

Journal of Neurology - Several genetic variants are associated with an increased risk for developing Parkinson’s Disease (PD) and limited genotype/phenotype correlation. Specifically,...     

Impact of drooling in Parkinson’s disease

Drooling is a well known problem in patients with Parkinson's disease (PD). The aim of this study was to investigate the severity and consequences of drooling in PD. A comprehensive drooling questionnaire was sent to 105 PD outpatients, who had volunteered drooling during a previous questionnaire (n = 216). Among 63 patients who responded and confirmed drooling, 27% experienced severe saliva loss. Social and emotional consequences were reported by 17% to 77% of patients, and significantly more often by those with severe drooling. We conclude that drooling is a frequent, disabling and apparently undertreated symptom of PD. History taking ought to be detailed and specific to understand the full impact of drooling for an individual patient. Therapeutic options should be evaluated more intensively.     

Pharmacotherapy of Parkinson’s disease in Germany

Treatment standards or guidelines have been developed for most features of Parkinson’s disease (PD). However, data on the actual treatment that is put into practice are scarce. In 2000, a nationwide survey on the topic of sudden onset of sleep (SOS) in PD was initiated among the members of the German patient support group (deutsche Parkinson–Vereinigung, dPV). A part of this mailed questionnaire survey covering the antiparkinsonian and concomitant medication of the participants is presented here. This study analyses data sets from more than 6,500 PD patients. The mean dopaminergic dose was equivalent to 599 ± 387 mg levodopa/die. The most frequently administered drugs were levodopa (94.2 %), dopamine agonists (DA) (71.7 %), amantadine (40.1 %), selegiline (27.6 %), entacapone (20.4 %), budipine (12.3 %), and anticholinergics (11.8 %). Costs of pharmacotherapy were estimated to be approximately € 399 million/year in Germany. PD drug therapy in general strongly depended on age, disease duration, and the level of care. The treatment guidelines were apparently not consistently followed underlining the need for their continuous propagation throughout the medical community. In addition our data suggest that non–motor symptoms in PD are not adequately treated and that concomitant sedative medication contributes to the occurrence of SOS.     

Romberg ratio coefficient in quiet stance and postural control in Parkinson’s disease

The aim of this study was to determine the function of visual afference in postural control in Parkinson patients. We enrolled 29 patients and 30 healthy controls. The stabilometry test was performed for posture and balance and Romberg ratio coefficients were calculated. In addition, the Berg Balance Scale and the 6-Minute Walking Test were administered to assess balance and functional exercise capacity; the Unified Parkinson’s Disease Rating Scale was used to determine the stage of the disease; and the Short Form (SF)-36 Health Survey was given to collect information on quality of life. Results: significantly longer Center of Pressure (CoP) sway lengths were observed in the parkinson group. The Romberg index for CoP length of sway in parkinson patients was 94.3?±?19.3%, versus 147.4?±?120.6% for the control group. (p?=?0.025). Conclusion: Parkinson patients use the increase in CoP sway length and ellipse area to stabilize their balance and sight does not facilitate static postural control as in healthy subjects.     

Neuroimaging in Parkinson’s disease

In this review, the potential role of positron emission tomography and single photon emission computed tomography as biological markers for diagnosing and following the progression of Parkinson’s disease (PD) is discussed. Their value for assessing the efficacy of putative neuroprotective agents in PD and for revealing the pharmacological changes underlying the symptomatology and complications of this disorder is also considered. It is concluded that in the future functional imaging will provide a valuable adjunct to clinical assessment when judging the efficacy of putative neuroprotective approaches to PD.     

Depression in Parkinson’s disease

Among the recently well appreciated non-motor symptoms in Parkinson’s disease (PD), depression plays a prominent role due to its frequency and impact on quality of life. However, depression may be confounded by motor symptoms, especially akinesia and other non-motor symptoms such as apathy, anxiety and dementia. Data on specific diagnostic tools or treatment for depressive symptoms in PD patients are still sparse. Here we summarize an expert opinion based on available data and clinical experience.