Cognitive and behavioural assessment of parkinsonian syndromes at onset: a longitudinal study

Background: cognitive impairment is one of the non motor features widely descripted in parkinsonian syndrome, it has been related to the motor characteristics of the parkinsonian syndrome, associated with neuropsychiatric dysfunction and the characteristic sleep and autonomic features. It has been shown to be highly prevalent at all disease stages and to contribute significantly to disability. Objectives: aim of this study is to evaluate longitudinally the cognitive and behavioral characteristics of patients with a parkinsonian syndrome at onset; to describe the cognitive and behavioral characteristics of each parkinsonian syndrome; to define in PD patients at onset the presence of MCI or Parkinson disease dementia; to correlate the cognitive and behavioral characteristics with the features of the parkinsonian syndrome and with the associated sleep and autonomic features. Results: we recruited 55 patients, 22 did not present cognitive impairment both at T0 and at T1. 18 patients presented a progression of cognitive impairment. Progressive cognitively impaired patients were older and presented the worst motor phenotype. Progression of cognitive impairment was not associated to sleep and autonomic features. Conclusion: the evaluation of cognitive impairment could not be useful as a predictor of a correct diagnosis but each non motor domain will help to clarify and characterize the motor syndrome. The diagnosis of parkinsonian disorders lies in building a clinical profile in conjunction with other clinical characteristics such as mode of presentation, disease progression, response to medications, sleep and autonomic features.

Visual hallucinations in the Parkinsonian syndromes

Differential clinical diagnosis of the parkinsonian syndromes,viz., Parkinson's disease (PD), progressive supranuclear palsy (PSP), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and corticobasal degeneration (CBD) can be difficult. Visual hallucinations, however, are a chronic complication of some parkinsonian disorders and their presence may be a useful aid to diagnosis. The visual hallucinations in parkinsonism are often recurrent, well-formed, and detailed and occur in a significant proportion of cases of DLB and PD but are less common in PSP, MSA, and CBD. Hallucinations in PD often occur later in the disease and are complex, with flickering lights, and illusionary misconceptions often preceding the most common manifestation, viz., stereotypical colourful images. Hallucinations in DLB, however, are often present earlier in the disease and are similar to those in the 'misidentification syndromes', 'visual agnosias', and in 'delerium' but differ from those produced by hallucinogenic drugs such as LSD. Most typically in DLB, the hallucinations involve people or animals invading the patient's home but may also include inanimate objects and the appearance of writing on walls or ceilings. Visual hallucinations may involve a number of brain mechanisms including a change in the balance of neurotransmitter activity between the cholinergic and monoaminergic systems and may be a specific consequence of Lewy body (LB) pathology in brain stem nuclei. Ocular and retinal pathology may also contribute to hallucinations by reducing occipital stimulation. Hence, in patients with unclassifiable or with indeterminate parkinsonian symptoms, the presence of visual hallucinations should be regarded as a 'red flag' symptom indicating underlying Lewy body pathology and therefore, supporting a diagnosis of PD or DLB rather than PSP, MSA, or CBD. The presence of early visual hallucinations would support a diagnosis of DLB rather than PD. © 2013 Nova Science Publishers, Inc. All rights reserved.

Eye movement problems and differential diagnosis of the parkinsonian syndromes

Differential clinical diagnosis of the parkinsonian syndromes, viz., Parkinson’s disease (PD), progressive supranuclear palsy (PSP), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) can be difficult. Eye movement problems, however, are a chronic complication of many of these disorders and may be a useful aid to diagnosis. Hence, the presence in PSP of vertical supranuclear gaze palsy, fixation instability, lid retraction, blepharospasm, and apraxia of eyelid opening and closing is useful in separating PD from PSP. Moreover, atypical features of PSP include slowing of upward saccades, moderate slowing of downward saccades, the presence of a full range of voluntary vertical eye movements, a curved trajectory of oblique saccades, and absence of square-wave jerks. Downgaze palsy is probably the most useful diagnostic clinical symptom of PSP. By contrast, DLB patients are specifically impaired in both reflexive and saccadic execution and in the performance of more complex saccadic eye movement tasks. Problems in convergence in DLB are also followed by akinesia and rigidity. Abnormal ocular fixation may occur in a significant proportion of MSA patients along with excessive square-wave jerks, a mild supranuclear gaze palsy, a gaze-evoked nystagmus, a positioning down-beat nystagmus, mild-moderate saccadic hypometria, impaired smooth pursuit movements, and reduced vestibulo-ocular reflex (VOR) suppression. There may be considerable overlap between the eye movement problems characteristic of the various parkinsonian disorders, but taken together with other signs and symptoms, can be a useful aid in differential diagnosis, especially in the separation of PD and PSP.

Neuropathology of Basal Ganglia and its role in the Parkinsonian syndromes with special reference to the Globus pallidus

The globus pallidus, together with the striatum (caudate nucleus and putamen), substantia nigra, nucleus accumbens, and subthalamic nucleus constitute the basal ganglia, a group of nuclei which act as a single functional unit. The basal ganglia have extensive connections to the cerebral cortex and thalamus and exert control over a variety of functions including voluntary motor control, procedural learning, and motivation. The action of the globus pallidus is primarily inhibitory and balances the excitatory influence of other areas of the brain such as the cerebral cortex and cerebellum. Neuropathological changes affecting the basal ganglia play a significant role in the clinical signs and symptoms observed in the ‘parkinsonian syndromes’ viz., Parkinson’s disease (PD), progressive supranuclear palsy (PSP), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and corticobasal degeneration (CBD). There is increasing evidence that different regions of the basal ganglia are differentially affected in these disorders. Hence, in all parkinsonian disorders and especially PD, there is significant pathology affecting the substantia nigra and its dopamine projection to the striatum. However, in PSP and MSA, the globus pallidus is also frequently affected while in DLB and CBD, whereas the caudate nucleus and/or putamen are affected, the globus pallidus is often spared. This chapter reviews the functional pathways of the basal ganglia, with special reference to the globus pallidus, and the role that differential pathology in these regions may play in the movement disorders characteristic of the parkinsonian syndromes.

Medium-term prognosis of an incident cohort of parkinsonian patients compared to controls

Funding This work was supported by Parkinson's UK (grant numbers G0502, G0914), BMA Doris Hillier Award, the BUPA Foundation, NHS Grampian Endowments, RS MacDonald Trust.

Quantitative diffusion tensor imaging detects dopaminergic neuronal degeneration in a murine model of Parkinson's disease.

Early diagnosis of Parkinson's disease (PD) is required to improve therapeutic responses. Indeed, a clinical diagnosis of resting tremor, rigidity, movement and postural deficiencies usually reflect >50% loss of the nigrostriatal system in disease. In a step to address this, quantitative diffusion tensor magnetic resonance imaging (DTI) was used to assess nigrostriatal degeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication model of dopaminergic nigral degeneration. We now demonstrate increased average diffusion (p<0.005) and decreased fractional anisotropy (p<0.03) in the substantia nigra (SN) of 5- to 7-day MPTP-treated animals when compared to saline controls. Transverse diffusivity demonstrated the most significant differences (p < or = 0.002) and correlated with the numbers of SN dopaminergic neurons (r=-0.75, p=0.012). No differences were found in the striatum, corpus callosum, cerebral cortex, or ventricles. These results demonstrate that DTI may be used as a surrogate biomarker of nigral dopaminergic neuronal degeneration.

Cannabinoids and tremor induced by motor-related disorders: friend or foe?

Tremor arises from an involuntary, rhythmic muscle contraction/relaxation cycle and is a common disabling symptom of many motor-related diseases such as Parkinson disease, multiple sclerosis, Huntington disease, and forms of ataxia. In the wake of anecdotal, largely uncontrolled, observations claiming the amelioration of some symptoms among cannabis smokers, and the high density of cannabinoid receptors in the areas responsible for motor function, including basal ganglia and cerebellum, many researchers have pursued the question of whether cannabinoid-based compounds could be used therapeutically to alleviate tremor associated with central nervous system diseases. In this review, we focus on possible effects of cannabinoid-based medicines, in particular on Parkinsonian and multiple sclerosis-related tremors and the common probable molecular mechanisms. While, at present, inconclusive results have been obtained, future investigations should extend preclinical studies with different cannabinoids to controlled clinical trials to determine potential benefits in tremor.

The most severe parkinsonian patients are most improved with duodenal levodopa infusion

Objectives:To find variables correlated to improvement with intraduodenal levodopa/carbidopa infusion (Duodopa) in order to identify potential candidates for this treatment. Two clinical studies comparing Duodopa with oral treatments in patients with advanced Parkinson’s disease have shown significant improvement in percent on-time on a global treatment response scale (TRS) based on hourly and half-hourly clinical ratings and in median UPDRS scores.Methods:Data from study 1 comparing infusion with Sinemet CR (12 patients, Nyholm et al, Clin Neuropharmacol 2003; 26(3): 156-163) and study 2 comparing infusion with individually optimised conventional combination therapies (18 patients, Nyholm et al, Neurology, in press) were used. Measures of severity were defined as total UPDRS score and scores for sections II and III, percent functional on-time and mean squared error of ratings on the TRS and as mean of diary questions about mobility and satisfaction (only study 2). Absolute improvement was defined as difference in severity, and relative improvement was defined as percent absolute improvement/severity on oral treatment. Pearson correlation coefficients between measures of improvement and other variables were calculated.Results:Correlations (r2>0.28, p<0.05) between severity during oral treatment and absolute improvement on infusion were found for: Total UPDRS, UPDRS III and TRS ratings (studies 1 and 2) and for diary question 1 (mobility) and UPDRS II (study 2). Correlation to relative improvement was found for total UPDRS (study 2, r2=0.47). Figure 1 illustrates absolute improvement in total UPDRS vs. total UPDRS during oral treatment (study 2).Conclusion:Correlating different measures of severity and improvement revealed that patients with more severe symptoms were most improved and that the relation between severity and improvement was linear within the studied groups. The result, which was reproducible between two clinical studies, could be useful when deciding candidates for the treatment.

First-principle data-driven models for assessment of motor disorders in Parkinson’s disease

Parkinson’s disease (PD) is an increasing neurological disorder in an aging society. The motor and non-motor symptoms of PD advance with the disease progression and occur in varying frequency and duration. In order to affirm the full extent of a patient’s condition, repeated assessments are necessary to adjust medical prescription. In clinical studies, symptoms are assessed using the unified Parkinson’s disease rating scale (UPDRS). On one hand, the subjective rating using UPDRS relies on clinical expertise. On the other hand, it requires the physical presence of patients in clinics which implies high logistical costs. Another limitation of clinical assessment is that the observation in hospital may not accurately represent a patient’s situation at home. For such reasons, the practical frequency of tracking PD symptoms may under-represent the true time scale of PD fluctuations and may result in an overall inaccurate assessment. Current technologies for at-home PD treatment are based on data-driven approaches for which the interpretation and reproduction of results are problematic.  The overall objective of this thesis is to develop and evaluate unobtrusive computer methods for enabling remote monitoring of patients with PD. It investigates first-principle data-driven model based novel signal and image processing techniques for extraction of clinically useful information from audio recordings of speech (in texts read aloud) and video recordings of gait and finger-tapping motor examinations. The aim is to map between PD symptoms severities estimated using novel computer methods and the clinical ratings based on UPDRS part-III (motor examination). A web-based test battery system consisting of self-assessment of symptoms and motor function tests was previously constructed for a touch screen mobile device. A comprehensive speech framework has been developed for this device to analyze text-dependent running speech by: (1) extracting novel signal features that are able to represent PD deficits in each individual component of the speech system, (2) mapping between clinical ratings and feature estimates of speech symptom severity, and (3) classifying between UPDRS part-III severity levels using speech features and statistical machine learning tools. A novel speech processing method called cepstral separation difference showed stronger ability to classify between speech symptom severities as compared to existing features of PD speech. In the case of finger tapping, the recorded videos of rapid finger tapping examination were processed using a novel computer-vision (CV) algorithm that extracts symptom information from video-based tapping signals using motion analysis of the index-finger which incorporates a face detection module for signal calibration. This algorithm was able to discriminate between UPDRS part III severity levels of finger tapping with high classification rates. Further analysis was performed on novel CV based gait features constructed using a standard human model to discriminate between a healthy gait and a Parkinsonian gait. The findings of this study suggest that the symptom severity levels in PD can be discriminated with high accuracies by involving a combination of first-principle (features) and data-driven (classification) approaches. The processing of audio and video recordings on one hand allows remote monitoring of speech, gait and finger-tapping examinations by the clinical staff. On the other hand, the first-principles approach eases the understanding of symptom estimates for clinicians. We have demonstrated that the selected features of speech, gait and finger tapping were able to discriminate between symptom severity levels, as well as, between healthy controls and PD patients with high classification rates. The findings support suitability of these methods to be used as decision support tools in the context of PD assessment.

Sleep motor activity in parkinsonian syndromes at onset: a prospective study to determine potential diagnostic and prognostic markers

Aim of this study is to describe the possible diagnostic value of sleep disturbances in the differential diagnosis of neurodegenerative diseases characterized by parkinsonism at onset. 42 consecutive patients with parkinsonian features and disease duration up to 3 years were included in the BO-ProPark study. Each patient was evaluated twice, at baseline (T0) and 16 months later (T1). Patients were diagnosed as Parkinson disease (PD, 27 patients), PD plus (PD with cognitive impairment/dementia or dysautonomia, 4 patients) and parkinsonian syndrome (PS, 11 patients). All patients underwent a full night video-polysomnography scored by a neurologist blinded to the clinical diagnosis. Sleep efficiency and total sleep time were reduced in all patients; wake after sleep onset was higher in patients with atypical parkinsonisms than in PD patients. No significant differences between groups of patients were detected in other sleep parameters. The mean percentage of epochs with enhanced tonic muscle EMG activity during REM sleep was higher in PD plus and PS than in PD. No difference in phasic muscle EMG activity during REM sleep was seen between the two groups. REM behaviour disorder was more frequent in PD plus and PS than in PD patients. Our data suggest that REM sleep motor control is more frequently impaired at disease onset in patients with PS and PD plus compared to PD patients. The presence of RBD or an enhanced tonic muscle EMG activity in a patient with recent onset parkinsonian features should suggest a diagnosis of atypical parkinsonism, rather than PD. More data are needed to establish the diagnostic value of these features in the differential diagnosis of parkinsonisms. The evaluation of sleep disorders may be a useful tool in the differential diagnosis of parkinsonism at onset.

[Vestibular disorders in Parkinson patients]

Patients suffering from Parkinson's disease frequently complain of dizziness, postural instability and falls. Vestibular tests have been performed in 30 parkinsonian patients and in 28 controls. The results suggest a central vestibular disturbance in Parkinson's disease which correlates with the clinical disability. This vestibular disturbance is assumed to be due to dysfunction of the nigro-striato-collicular tracts.

Upper body musculoskeletal disorders among Australian occupational therapy students

Although upper body musculoskeletal disorders (MSDs) represent an increasingly important issue for university students, few if any studies have targeted the occupational therapy faculty. Given this dearth of information, it was considered necessary to investigate a cross-section of Australian occupational therapy students by means of an established questionnaire survey. Completed replies were obtained from 95.7%, 100% and 97.7% (n = 44, 55 and 48) of students in the first, second and fourth years of a large occupational therapy school in northern Queensland, Australia.---------- The 12-month period prevalence of MSDs was as follows: neck (67.4%), shoulder (46.3%) and upper back (39.5%). Three-quarters of all students (75.5%) reported an MSD occurring in at least one of these body regions. Over half (56.5%) reported an MSD over 2 days' duration in the past year. Almost 40% (39.5%) reported an MSD that had affected their daily life, while one-quarter (25.2%) needed some type of treatment.---------- Logistic regression indicated that students aged over 21 years were almost four times more likely to report shoulder-related MSD (OR 3.7, 95%CI: 1.4-10.2). Year of study in the occupational therapy course was another important MSD correlate, with adjusted odds ratios ranging from 3.3 at the upper back (OR 3.3, 95%CI: 1.2-9.6) to 10.9 at the neck (OR 10.9, 95%CI: 3.2-43.8). Computer usage also incurred a certain degree of risk, with students who spent over 5 hours per week on the computer having an increased risk of MSD at the neck (OR 5.0, 95%CI: 1.3-21.5) and shoulder (OR 4.7, 95%CI: 1.4-18.3).---------- Overall, this study suggests that Australian occupational therapy students have a large burden from MSDs in the upper body region, even more so than other student groups and some working populations. Since the distribution of MSD risk is not uniform among them, interventions to help reduce these conditions need to be carefully targeted. Further longitudinal investigations would also be useful in determining the mechanisms and contributory factors for MSDs among this unique student population.