Audiovisual cues can enhance sit-to-stand in patients with Parkinson's disease.

We investigated whether preparatory signals, in the form of audiovisual cues, could enhance the performance of sit-to-stand (STS) in Parkinson's disease (PD) patients. Fifteen patients and fifteen control subjects similar in age, gender, weight, and height were examined. All subjects were instructed to carry out STS under self-initiated and cue-initiated conditions. A PEAK Motion Analysis System and two force plates were synchronized to record kinematic and kinetic data. In patients with PD, the addition of audiovisual cues was found to increase hip flexion and knee extension torques and decrease the time-to-peak joint torques, as well as increase peak horizontal and vertical velocities of the body center of mass and decrease the time taken to complete STS. Consequently, the performance of STS in these patients approached that of control subjects. In fact, during cue-initiated STS, no difference was found between the patient and control groups for the time-to-peak of all joint torques, the peak horizontal and vertical velocities, and the time taken to complete STS. Our findings thus demonstrated that audiovisual cues were effective in enhancing STS in patients with PD. These feed-forward signals could have enhanced the defective motor preparatory phase, thus leading to improved performance of the STS task. These findings provide a scientific basis for the use of audiovisual signals to enhance STS performance in patients with PD.     

Planning and realisation of complex intentions in patients with Parkinson's disease

BACKGROUND: There is some evidence that patients with Parkinson's disease may impaired in prospective memory performance (planning and self initiated realisation of delayed intentions). Little is known about the effect of the disease on distinct phases of prospective memory and the potential mechanisms underlying these effects. OBJECTIVE: To investigate intention formation, intention retention, intention initiation, and intention execution of patients with Parkinson's disease and test for the mediating influence of working memory, inhibition, short term retrospective memory, and divided attention. METHODS: 16 patients with Parkinson's disease and 16 age and education matched normal controls were given a complex event based prospective memory task which differentiates four phases of prospective remembering. In addition, participants completed tasks assessing potential cognitive mediators. RESULTS: On the prospective remembering task, Parkinson patients were impaired in the intention formation phase and showed a trend towards impairment in the intention initiation. In contrast, there were no impairments of retrospective intention retention or the fidelity with which the patients executed their previously developed plan. The group effects were related to interindividual differences in working memory span. CONCLUSIONS: The results suggest that the planning phase of prospective remembering is specifically impaired in Parkinson's disease, and that the impairment is related to working memory deficit. In contrast, even when complex intentions have to be remembered, the retrospective storage of intentions to be performed is not impaired.     

Patients with Parkinson''s disease can employ a predictive motor strategy.

We have tested the hypothesis that predictive motor behaviour is abnormal in Parkinson's disease. In the first experiment elbow movements were performed to track a moving spot on an oscilloscope screen. The performance of 12 patients with Parkinson's disease and eight age-matched control subjects was measured when tracking a repeated pattern under two conditions. In the first condition subjects were not aware of the repetitive nature of the tracking task whilst in the second condition they were. For both groups tracking error and tracking lag were less when aware of the repetition. In the second experiment wrist movements were studied. Five age-matched controls were compared with five patients, studied on and off drugs. In this experiment the performance tracking a repeated pattern was compared to that tracking unpredictable patterns. Tracking lags were reduced to very low values (less than 20 ms) in response to the repeated pattern for both groups. This was true even when the patients were relatively immobile off drugs. We conclude that patients with Parkinson's disease are capable of predictive motor behaviour although such a strategy does not always confer as great an advantage in reducing tracking error in patients compared with control subjects.     

The speed of sit-to-stand can be modulated in Parkinson's disease.

OBJECTIVE: To evaluate whether Parkinsonian patients could modify the speed of a sit-to-stand (STS) task to the same extent as that of healthy subjects. METHODS: Twenty Parkinsonian patients and 20 control subjects were instructed to stand up at a natural and fast speed. Kinematic data and kinetic data were recorded. RESULTS: Parkinsonian patients were significantly slower than healthy individuals during STS at a natural speed. When required to perform STS task at a fast speed, these patients could increase both peak horizontal and vertical velocities of the task, by significantly increasing hip and ankle dorsiflexion torques and the rate of torque production, just as the control subjects did. In fact, no difference was found for the percentage changes in both peak velocities and movement time between the two groups, though similar between-group differences during STS at a natural speed still existed at a fast speed. CONCLUSIONS: Parkinsonian patients had problems in generating adequate lower limb joint torques and in the rate of torque production when performing STS at a natural speed. However, these patients were capable of increasing the speed of their STS with the same percentage changes as those of healthy subjects. SIGNIFICANCE: The capability of Parkinsonian patients for increasing movement speed gives new insights to rehabilitation strategy.     

Semantic priming in Parkinson's disease: evidence for delayed spreading activation.

Nineteen persons with Parkinson's disease (PD) and 19 matched control participants completed a battery of online lexical decision tasks designed to isolate the automatic and attentional aspects of semantic activation within the semantic priming paradigm. Results highlighted key processing abnormalities in PD. Specifically, persons with PD exhibited a delayed time course of semantic activation. In addition, results suggest that experimental participants were unable to implicitly process prime information and, therefore, failed to engage strategic processing mechanisms in response to manipulations of the relatedness proportion. Results are discussed in terms of the 'Gain/Decay' hypothesis (Milberg, McGlinchey-Berroth, Duncan, & Higgins, 1999) and the dopaminergic modulation of signal to noise ratios in semantic networks.     

Selective delayed response deficits in Parkinson's and Alzheimer's disease

Experimental paradigms adopted from animal models were used to contrast the functional anatomy of frontal systems involved in Alzheimer's disease and the dementia of Parkinson's disease. Patients with Parkinson's disease with dementia were compared with patients with Alzheimer's disease, and nondemented patients with Parkinson's disease, and normal controls. The tasks administered, delayed alternation and delayed response (DR), are sensitive to frontal system damage. Different aspects of each task are mediated by separate frontosubcortical neuronal networks. Patients with Parkinson's disease with dementia were significantly impaired only on DR, whereas patients with Alzheimer's disease were impaired on DR and delayed alternation, even though both groups were equated for severity of dementia. Although dysfunction in the frontal lobes, and/or their subcortical connections, is implicated in both Parkinson's and Alzheimer's disease, dorsolateral frontal systems appear primarily impaired in Parkinson's disease, whereas dorsolateral frontal impairment combined with other regions, possibly orbitofrontal, are prominent in Alzheimer's disease.     

Cognitive processes involved in delayed non-matching-to-sample performance in Parkinson's disease

Visual recognition memory was assessed in terms of delay duration, memory load and amount of interference(s) in non-demented patients with Parkinson's disease (PD) using an automated delayed non-matching-to-sample (DNMS) task with trial-unique stimuli. Special attention was focused on the different cognitive functions engaged by these patients in solving this recognition memory task. Thirteen patients with PD, carefully selected according to their stable regimen and anticholinergic medication, were compared to 12 controls matched by age and educational level. Besides the DNMS task, a neuropsychological battery that included tasks carefully selected according to processes potentially required to perform the DNMS task (e.g. attention, executive functions, visual discrimination and motor speed) was administered to the subjects. As compared with controls, patients with PD showed a deficit on most DNMS subscores, except those requiring the least cognitive load. The correlative analysis between the DNMS and other neuropsychological tasks suggests involvement of long-term memory mainly in the DNMS performance for the control group, contrasting with a major involvement of executive functions for the patients with PD. These data indicate that visual recognition memory impairment in non-demented patients with PD is largely due to an executive dysfunction, notably in working memory. Several hypotheses are proposed concerning the neuronal substrates underlying the impairment on the visual DNMS task in PD.     

Fatigue in patients with Parkinson's disease.

OBJECTIVE: To compare the prevalence of fatigue in patients with Parkinson's disease (PD) with that in healthy elderly people and to explore the suggestion that fatigue is an independent symptom of PD. DESIGN: Questionnaire survey. SETTING: Community-based population. PATIENTS AND CONTROL SUBJECTS: 233 patients derived from a prevalence study in the county of Rogaland, Norway and 100 healthy elderly people with the same age and sex distribution as the patients with PD. MAIN OUTCOME MEASURE: A score for fatigue was obtained by combining the results from the rating scale for low energy in the Nottingham Health Profile (NHP) with the results obtained from a 7-point scale devised to evaluate fatigue. RESULTS: 44.2% of the patients with PD and 18% of the healthy elderly control subjects reported fatigue. Fatigue was associated with depression, dementia, disease severity, disease duration, levodopa dose, and the use of sleeping pills. In a multivariate analysis, only depressive symptoms reached statistical significance. The prevalence of fatigue in patients with PD who were not depressed, demented, or had a sleeping disturbance was similar to that found in the total PD population. CONCLUSION: Fatigue is a common symptom in PD. Although fatigue correlated with depressive symptoms, patients with PD who did not have depression, dementia, or sleep disturbances also reported a high prevalence of this symptom. This supports the hypothesis that fatigue is an independent symptom of PD overlapping with, but not causally related to, the concurrence of depressive symptoms.     

Parkinson's disease with late Pick's dementia.

We report a case in which typical clinical features of idiopathic Parkinson's disease existed for seven years prior to the development of significant behavioral and cognitive changes and severe dementia. The patient presented with right-sided resting tremor, bradykinesia, and rigidity, which were highly responsive to levodopa. Serial neuropsychological evaluation revealed no evidence of dementia until late in the disease. The patient deteriorated rapidly eight years into the disease, requiring full care. She died 16 years after symptom onset and post-mortem neuropathological analysis revealed Lewy body Parkinson's disease and Pick's disease. To our knowledge, this is the first non-familial case with this combination of clinical history and pathologically confirmed disease to be reported in the literature. The absence of a family history of any neurological disease sets this case apart from the recently described genetic cases of frontotemporal dementia with Parkinsonism linked to chromosome 17. In addition, the relatively late onset of dementia in frontotemporal dementia is atypical. While there is considerable debate regarding the cause of dementia in idiopathic Parkinson's disease, our case illustrates that Pick's disease is one such cause.     

Comparison of dementia with Lewy bodies to Alzheimer's disease and Parkinson's disease with dementia.

We compared the clinical and neuropsychological pattern of dementia with Lewy bodies (DLB) to Alzheimer's disease (AD) and Parkinson's disease with dementia (PD-d). Sixteen patients clinically diagnosed with DLB were compared with two groups of patients with PD-d (n = 15) and AD (n = 16) matched for level of dementia. Isolated cognitive impairment was the most common form of presentation in AD (93.8%) and DLB (31.3%) groups, while parkinsonism was in 100% of PD-d subjects. Psychoses associated with cognitive impairment at the beginning of the disease were more frequent in DLB patients (31.3%) than in AD (6.3%) and PD-d (0%) groups. There were no significant differences in Unified Parkinson Disease Rating Scale motor-subscale scores between DLB and PD-d patients. DLB and PD-d patients performed significantly worse on attentional functions and better on memory tests than AD. DLB patients also showed lower scores than AD subjects on visual memory, visuoperceptive, and visuoconstructive tests. No significant differences were found between PD-d group and DLB subjects on any neuropsychological test. We were unable to find any differences in cognitive tasks between PD-d and DLB subjects. Clinical features and neuropsychological deficiencies of DLB (attentional, visuoperceptive, and visuoconstructive deficits) and PD (attentional deficits) compared to AD (amnesic syndrome) can contribute to accurate identification of these entities and to the understanding of the neuropathological and neurochemical substrate underlying these diseases.     

Depression in patients with Parkinson's disease.

Parkinson's disease (PD) is a disabling neurodegenerative condition commonly complicated by the existence of comorbid depression. The prevalence rates of depression in this patient group have been reported to be as high as 40%. Currently, depression in PD is undertreated; there have been few controlled clinical trials of antidepressants in this patient group. Patients with PD are usually elderly and often administered a range of medication, therefore the choice of antidepressant must be undertaken with care. Tricyclic antidepressants (TCAs) have been studied in patients with PD and comorbid depression; however, the risk of anticholinergic side-effects means that their use is largely avoided. Selective serotonin reuptake inhibitors have comparable efficacy to the TCAs and a better tolerability profile in patients with depression; they are rapidly being considered as first-line therapy for PD patients with depression. Clinical studies in this patient group are warranted. This article reviews the characteristics of comorbid depression in patients with PD and discusses the treatment options available.     

Cerebrospinal fluid antibodies to coronavirus in patients with Parkinson's disease.

The etiology of Parkinson's disease remains unknown, and a search for environmental agents continues. In 1985, Fishman induced infection of the basal ganglia by a coronavirus in mice. Although coronavirus is recognized primarily as a respiratory pathogen in humans, its affinity for the basal ganglia led us to investigate its possible role in human Parkinson's disease. The cerebrospinal fluid of normal controls (CTL) (n = 18), and patients with Parkinson's disease (PD (n = 20) and other neurological disease (OND) (n = 29) was analyzed in a blinded manner by enzyme-linked immunosorbent assay [measurements in optical density (OD) units] for antibody response to four coronavirus antigens: mouse hepatitis virus JHM (J) and A59 (A), and human coronavirus 229E (E) and OC43 (O). When compared with CTL, PD patients had an elevated (p less than 0.05) mean OD response to J (0.0856 vs. 0.0207) and A (0.1722 vs. 0.0636). Response (p greater than 0.05) to O (0.0839 vs. 0.0071) was greater than that to E (0.1261 vs. 0.0743). When compared to OND, PD patients had an elevated mean OD response to J (0.0856 vs. 0.0267, p less than 0.05). Responses (p greater than 0.05) to A (0.1722 vs. 0.0929) and O (0.0839 vs. 0.0446) were greater than that to E (0.1261 vs. 0.0946). These results suggest that there may be an association between coronavirus and PD.     

Recessive Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disease caused by loss of dopaminergic neurons in the substantia nigra pars compacta. Although the etiology of PD remains unclear, it is now clear that genetic factors contribute to the pathogenesis of the disease. Recently, several causative genes have been identified in monogenic forms of PD. Accumulating evidence indicates that their gene products play important roles in mitochondrial function, oxidative stress response, and the ubiquitin-proteasome system, which are also implicated in sporadic PD, suggesting that these gene products share a common pathway to nigral degeneration in both familial and sporadic PD. Here, we review recent advances in knowledge about genes associated with recessive PD, including parkin, PINK1, and DJ-1.     

Parkinson's disease with camptocormia

Background

Camptocormia is defined as an abnormal flexion of the trunk that appears when standing or walking and disappears in the supine position. The origin of the disorder is unknown, but it is usually attributed either to a primary or a secondary paravertebral muscle myopathy or a motor neurone disorder. Camptocormia is also observed in a minority of patients with parkinsonism.

Objective

To characterise the clinical and electrophysiological features of camptocormia and parkinsonian symptoms in patients with Parkinson''s disease and camptocormia compared with patients with Parkinson''s disease without camptocormia.

Methods

Patients with parkinsonism and camptocormia (excluding patients with multiple system atrophy) prospectively underwent a multidisciplinary clinical (neurological, neuropsychological, psychological, rheumatological) and neurophysiological (electromyogram, ocular movement recording) examination and were compared with age‐matched patients with Parkinson''s disease without camptocormia.

Results

The camptocormia developed after 8.5 (SD 5.3) years of parkinsonism, responded poorly to levodopa treatment (20%) and displayed features consistent with axial dystonia. Patients with camptocormia were characterised by prominent levodopa‐unresponsive axial symptoms (ie, axial rigidity, gait disorder and postural instability), along with a tendency for greater error in the antisaccade paradigm.

Conclusion

We suggest that (1) the salient features of parkinsonism observed in patients with camptocormia are likely to represent a specific form of Parkinson''s disease and camptocormia is an axial dystonia and (2) both camptocormia and parkinsonism in these patients might result from additional, non‐dopaminergic neuronal dysfunction in the basal ganglia.Camptocormia is defined as an abnormal flexion of the trunk that appears when standing or walking and disappears in the supine position (fig 1​1).). This rare symptom, usually found in patients >65 years of age, is often attributed to normal ageing and is not diagnosed. The term “camptocormia” is derived from the Greek words “kamptos” (to bend) and “kormos” (trunk), and was coined by the French neurologist Souques.¹ The authors reported a soldier, who had a forced posture with a bent‐forward trunk after a gunshot wound. The patient was reportedly cured after a psychotherapeutic interview and subsequent application, in narcosis, of a plaster jacket that was removed after 2 days. Souques even suggested that the disorder could be cured completely and permanently by means of a persuasive galvanisation or faradisation of the dorsolumbar region, and termed the condition “cyphose hystérique” (“hysterical kyphosis”). Although a few authors pointed out that patients with an organic condition such as spondylitis should be differentiated from those with hysterical kyphosis, a psychogenic explanation for the disorder prevailed, owing to the many cases similar to those of Souques that were reported during the First and Second World Wars.^2,3,4,5,6Open in a separate windowFigure 1 Drawing of a patient with Parkinson''s disease and camptocormia (Bibliothèque Charcot, Hôpital de la Salpêtrière; left) and photographs of one of the patients studied (camptocormia appears when the patient is standing or walking and disappears in the supine position; right). Patient consent was obtained for publication of this figure.In 1995, Laroche et al⁷ reported 37 patients with camptocormia who were compared with 15 age‐matched patients without camptocormia but with posterior interapophysial osteoarthritis and elderly patients surgically treated for narrowing of the lumbar canal. In patients with camptocormia, magnetic resonance imaging (MRI) showed features consistent with circumscribed myopathy in the paravertebral muscles, and it was stated that camptocormia might be ascribed to a primary paravertebral myopathy.⁸ The spectrum of these neuromuscular disorders was subsequently extended to myasthenia gravis, nemaline myopathy,^9,10 amyotrophic lateral sclerosis,¹¹ inclusion body myositis, polymyositis^9,12 and miscellaneous causes such as paraneoplastic disorder¹³ and valproate toxicity¹⁴ (see also review by Azher and Jankovic¹⁵). None of the above studies, however, mentioned the presence of parkinsonism. Indeed, in the few studies that have dealt with the issue of camptocormia and parkinsonism, the coexistence of these disorders was thought to result from the incidental occurrence of Parkinson''s disease and neuromuscular disorders,^9,15,16 features of multiple systemic atrophy (MSA),^9,15 or a rare type of dystonia peripherally induced¹⁵ or of unknown origin.^9,15,17 Although some studies were the first to draw attention to the disorder,¹⁷ the nosological position and the origin of this unusual symptom in association with parkinsonism remain unclear, as do the precise clinical features of this entity.The aim of the present prospective study was to characterise a selected sample of patients with parkinsonism and camptocormia and to compare them with age‐matched patients with Parkinson''s disease without camptocormia.     

Body weight in patients with Parkinson's disease.

There is some evidence suggesting that Parkinson's disease (PD) patients exhibit lower body weight when compared to age-matched healthy subjects. Low body mass index (BMI) is correlated with low bone mineral density, both of which are major risk factors for hip fractures. Possible determinants of weight loss in PD patients include hyposmia, impaired hand-mouth coordination, difficulty chewing, dysphagia, intestinal hypomotility, depression, decreased reward processing of dopaminergic mesolimbic regions, nausea, and anorexia as the side effects of medication, and increased energy requirements due to muscular rigidity and involuntary movements. It is unclear whether PD patients in general, or only a subgroup of those affected, definitely show lower BMI in the advanced stages of the disease. We therefore recommend that the body weight of PD patients be monitored monthly as the disease progresses, and that a patient's nutrition should be supplemented with sufficient amounts of vitamin D and calcium to reduce the risk of hip fractures and strengthen bone density. Because meal times may coincide with unpredictable off periods associated with akinesia and impaired hand-mouth coordination, PD patients also need flexible food schedules that accommodate the associated symptoms of this disease.     

Assessing comorbidity in patients with Parkinson's disease.

The aim of this study was to assess the accuracy of an interview-based assessment of comorbidity, in patients with Parkinson's disease (PD). The Cumulative Illness Rating Scale-Geriatric (CIRS-G) was completed (1) in an interview with 31 PD patients and their caregivers, and (2) by reviewing the patient's medical charts from their general practitioners. Based on the interview, all patients had some comorbidity, 84% had one or more moderate comorbid diseases. The most frequently affected organ systems were "lower gastrointestinal" and "genitourinary". The mean +/- SD total score of the interview-based (chart-based) CIRS-G was 6.9 +/- 3.8 (7.6 +/- 3.5) with a mean of 4.3 +/- 1.9 (5.0 +/- 1.9) affected organ systems and a mean of 2.1 +/- 1.7 (2.3 +/- 1.6) organ systems with at least moderate comorbidity per patient. The agreement (intraclass correlation coefficients) between the interview-based and chart-based assessments for the six summary scores ranged from 0.69 to 0.81. The agreement for the 14 organ systems ranged from 0.13 to 1.00 (weighted kappa); 12 had a K(w) above 0.40 (moderate agreement). The comorbidity summary scores had a moderate correlation with age and disability. The interview-based assessment of the CIRS-G is easy to apply and is an accurate method to assess comorbidity in patients with PD.     

Autonomic dysfunction in men with Parkinson's disease.

Forty-eight men with Parkinson's disease (PD) were interviewed utilizing a questionnaire which evaluated autonomic function. The study population included PD patients (mean age: 65.8 years, mean duration of PD: 8 years) and 32 elderly healthy nonparkinsonian males (mean age: 70.4 years). We found a significantly higher prevalence of the following symptoms of autonomic dysfunction in the parkinsonian patients: erectile dysfunction (60.4 vs. 37.5%), sensation of incomplete bladder emptying (41.6 vs. 15.6%), urgency (45.8 vs. 3.125%), constipation (43.9 vs. 6.25%), dysphagia (22.9 vs. 6.25%) and orthostatic dizziness (21.95 vs. 0%). Eighty-nine percent of parkinsonian patients had at least one of these autonomic symptoms, compared to 43% of control subjects (p less than 0.05). This study is the first comprehensive survey of autonomic symptomatology in PD compared to elderly healthy controls and confirms that autonomic nervous system dysfunction is a pervasive problem in PD. Erectile dysfunction is a significant problem in this patient group and contributes to deterioration in the quality of life.