帕金森病运动症状偏侧化的研究进展

帕金森病(PD)是一种以运动症状为主要表现的神经退行性疾病,常单侧起病,不同侧别的运动症状在疾病发展速度、非运动症状类型和治疗反应等方面存在差异。本文现围绕PD运动症状偏侧化的临床特点、潜在机制、影像表现及治疗差异等内容综述如下,以期为PD临床诊疗提供一定依据。     

Sound lateralization in Parkinson's disease

The symptoms primarily associated with Parkinson's disease (PD) are of a motor and cognitive nature, but sensory deficits may also be involved. Previous studies have reported disturbed spatial perception in visual and tactile tasks. We have investigated whether PD patients show deficits in auditory spatial perception. For this purpose, we employed a simple task involving left/right judgments about dichotic stimuli presented with various interaural time differences (ITD). The acuity of sound lateralization was significantly reduced in PD: the just noticeable difference (JND) in interaural time seen in PD patients was about twice that seen for age-matched healthy controls. We propose that this deficit may be related to a potential role of the basal ganglia in spatial hearing functions, as has been suggested by neurophysiological and neuroanatomical studies on animals.     

Novel nondopaminergic targets for motor features of Parkinson's disease: Review of recent trials

Neurotransmitters other than dopamine are recognized as having modulatory roles within the basal ganglia and can influence the basal ganglia dopaminergic system to alter activity of the direct and indirect pathways. Many nondopaminergic neurotransmitter systems have been implicated in the mechanisms contributing to the motor features of Parkinson's disease (PD). Thus, it is now well established that neurotransmitter systems, including glutamatergic, GABAergic, cholinergic, noradrenergic, serotonergic, opioidergic, histaminergic, and adenosinergic systems, are affected in the pathogenesis of PD. Nondopaminergic neurotransmitter systems are thus targets for the development of novel therapies for motor symptoms and motor complications in PD. Over the last 5 years, more than 20 randomized, control trials (RCTs) in PD investigating drugs that target several of these nondopaminergic neurotransmitter systems for the treatment of motor features have been completed. There are at least 15 additional RCTs that are ongoing or planned. Here, we review these RCTs to highlight the potential nondopaminergic pharmacological therapies for treatment of motor features of PD. Nondopaminergic drugs are not expected to replace dopaminergic strategies, but further development of these drugs will likely yield novel approaches with positive clinical implications. © 2012 Movement Disorder Society     

Survival in Parkinson's disease. Relation with motor and non-motor features

BackgroundSurvival in patients with Parkinson's disease is reduced as compared to the general population. We aimed to identify motor and non-motor features that predict mortality in Parkinson's disease.MethodsA broad range of motor and non-motor features were assessed in a hospital-based cohort of 414 patients with Parkinson's disease, who underwent five annual follow-up examinations including vital status assessment. Multivariable Cox's proportional hazards regression analysis was used to evaluate the association between baseline characteristics and mortality risk. Stepwise regression with backward elimination was carried out to determine the best model to predict mortality in Parkinson's disease.ResultsAfter a mean follow-up period of 4.3 years, 49 (11.8%) patients had died. In the stepwise regression model, predictors of mortality in Parkinson's disease were higher age, male sex, cognitive impairment, higher postural instability gait disorder score, and the presence of psychotic symptoms.ConclusionsHigher age, male sex, cognitive impairment, higher postural instability gait disorder score, and the presence of psychotic symptoms are independent predictors of decreased survival in Parkinson's disease. Mortality in Parkinson's disease thus seems to be affected mainly by non-dopaminergic and non-motor features.     

Prevalence of non motor features in a cohort of Parkinson's disease patients

Background

There is a lack of awareness among physicians of the considerable disability caused by non-motor symptoms (NMS) in PD. The aim of this work is to estimate the prevalence of NMS in a series of patients with Parkinson's disease (PD).

Materials and methods

We studied 112 patients with Parkinson's disease. Motor symptoms were scored on the Unified Parkinson's Disease Rating Scale (UPDRS) part III and the Hoehn and Yahr (HY) Scale. Other symptoms were quantified with the Non-Motor Symptom Questionnaire and Scale (NMSQuest and NMSS) as well as Minimental State Examination (MNSE).

Results

Analysis of the data from the NMSS showed that mood/cognition was the most commonly affected domain (prevalence rate = 87.5%), followed by sleep disturbance/fatigue second (78.6%). However, all other non-motor symptoms scored highly: gastrointestinal and urinary (76.8% for both), sexual dysfunction (73%), cardiovascular (70.5%) with significantly higher percentage in predominantly akinetic/rigid patients. Perceptual problems/hallucinations (9.9%) were infrequent in this population. Dementia was recorded in 22.3% of patients, most of them having a mild degree of dementia. UPDRS scores were correlated with total scores in both NMSQuest and NMSS.

Conclusions

Mood/cognition, sleep disorders, GIT, and sexual disorders were common non motor manifestations in this population of PD patients.     

Long-duration response to levodopa influences the pharmacodynamics of short-duration response in Parkinson's disease

The long duration response (LDR) to chronic levodopa treatment may mask the short-duration response (SDR) to a single dose of the drug in Parkinson's disease (PD). As a result, the measurement of SDR may be inaccurate for establishing levodopa dosing regimen in individual patients. To evaluate the possible contamination of SDR by LDR, we investigated in 16 patients with PD the characteristics of SDR to a single dose of levodopa administered after a prolonged washout from chronic therapy and after a 15-day treatment period with levodopa. Levodopa treatment produced a sustained LDR, and the SDR, measured on the 15th day of treatment, had lower magnitude and shorter duration than the response recorded after washout. Moreover, after treatment, SDR did not vary between patients with mild and severe PD, whereas, after washout, severely affected patients had larger but shorter SDR than mildly affected patients. The evaluation of SDR without the interference of LDR is critical in defining the characteristics of the therapeutic response to levodopa.     

Neurodegenerative 'overlap' syndrome: Clinical and pathological features of Parkinson's disease, motor neuron disease, and Alzheimer's disease

Parkinson's disease (PD), Alzheimer's disease (AD), and motor neuron disease (MND) share epidemiological, clinical, and pathological features. Few studies have reported comprehensively on individuals who demonstrate a neurodegenerative 'overlap' syndrome, comprising idiopathic parkinsonism, dementia, and motor neuron dysfunction. We describe clinical, electrophysiological, and pathological features in six patients with neurodegenerative 'overlap' syndrome. All had cardinal features of PD (duration 6-26 years), and any mixture of dementia (slowly advancing), fasciculations, hyperreflexia, Babinski signs and mild atrophy and weakness of distal muscles (slowly progressive). EMG often demonstrated a lack of denervation in conjunction with abnormal MEPs (high thresholds). Patients had either 6FD-PET or pathological studies consistent with PD. Pathological studies also demonstrated moderate numbers of neurofibrillary tangles and plaque formation, typically with sparing of motor neurons in the spinal cord. We conclude that neurodegenerative 'overlap' syndrome may represent forme frustes of traditionally accepted diagnostic categories. Patients with parkinsonism, fasciculations, hyperreflexia and mild atrophy are unlikely to demonstrate active denervation on EMG; their prognosis is better than for classical MND. Neurodegenerative overlap syndrome (clinicopathological mixtures of PD, AD, and MND) may develop in some individuals as a reflection of common etiology, pathogenesis or susceptibility.     

Treatment of motor and non-motor features of Parkinson's disease with deep brain stimulation

Deep brain stimulation (DBS) is an established procedure for the symptomatic treatment of Parkinson's disease. Several deep brain nuclei have been stimulated, producing a wide range of effects on the motor and non-motor symptoms of Parkinson's disease. Long-term, high-quality evidence is available for stimulation of the subthalamic nucleus and globus pallidus internus, both of which uniformly improve motor features, and for stimulation of the thalamic ventralis intermedius, which improves tremor. Short-term data are available for stimulation of other deep brain targets, such as the pedunculopontine nucleus and the centremedian/parafascicular thalamic complex. Some non-motor symptoms improve after DBS, partly because of motor benefit or reduction of drug treatment, and partly as a direct effect of stimulation. More evidence on the effects of DBS on non-motor symptoms is needed and specifically designed studies are warranted.     

Brain lateralization of motor imagery: motor planning asymmetry as a cause of movement lateralization

Movement asymmetry in humans and animals is often considered as being induced by the brain lateralization of the motor system. In the present work, the hemispheric asymmetry for motor planning as a cause of behavioral lateralization was examined. This study was carried out on normal volunteers and patients suffering unilateral brain damage caused by a stroke. Motor planning was evaluated by using the motor imagery of hand movement, a mental representation of a motor pattern that includes its internal simulation but not its real execution. The present study shows marked similarities between virtual movement executed during motor imagery and real movements. Thus, performance time showed a high correlation between real and virtual movements in the following conditions: (1) during dominant and non-dominant hand movements; (2) in simple and complex motor tasks; (3) in young control subjects; (4) in stroke patients; and (5) control subjects aged-matched to stroke patients. Brain strokes increased the performance time in both real and virtual movements. Left-brain strokes decreased the velocity of the real movements in both hands, whereas right-brain strokes mainly disturbed movements in the left hand. A similar effect was observed for virtual movements, suggesting a left-brain dominance for motor planning in humans. However, two-handed movement tasks suggest a complex interaction during motor planning, an interaction that facilitates motor performance during mirror movements and delays motor execution during non-mirror movements.     

Ophthalmologic features of Parkinson's disease

Patients with Parkinson's disease (PD) commonly complain of impaired visual function and difficulty reading, despite normal visual acuity. Although previous studies have evaluated contrast sensitivity, color vision, visuospatial processing, visual hallucinations, and ocular movements, none has systematically evaluated the ocular complaints and ocular findings of PD patients. Thirty patients with early untreated PD and 31 control subjects without neurologic or known ocular diseases were ophthalmologically evaluated for the frequency of visual complaints, dry eyes, blepharitis, visual hallucinations, reduced blink rate, blepharospasm, and convergence insufficiency. Ocular complaints suggesting ocular surface irritation, altered tear film, visual hallucinations, blepharospasm, decreased blink rate, and decreased convergence amplitudes were more common in PD patients than in control subjects. These findings likely account for many of the visual difficulties commonly encountered by PD patients. These ocular abnormalities frequently respond to treatment.     

Plasma antioxidant status and motor features in de novo Chinese Parkinson's disease patients

Purpose: This study aimed to explore plasma antioxidant status in de novo Chinese Parkinson's disease (PD) patients and investigate its relationship with specific motor features of PD. Patients and methods: Sixty-four de novo Chinese PD patients and 40 age- and sex-matched healthy controls were recruited. Each motor feature of PD patients was assessed by unified Parkinson's disease rating scale. Plasma antioxidant status, including plasma level of glutathione (GSH) and plasma activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), was detected using enzyme-linked immunosorbent assay. The relationship between the plasma antioxidant status and motor features of PD was evaluated by Spearman's coefficient. Results: Plasma GSH level and plasma activities of GSH-Px, CAT and SOD of PD patients were lower than those of healthy controls. Moreover, the declining activity of plasma CAT was related with the increasing mean postural instability and gait disorder (PIGD) score and growing age. In contrast, the severity of tremor was positively correlated with plasma SOD activity. Conclusion: Our study demonstrates that the plasma antioxidant status is impaired in de novo Chinese PD patients. The complex relationship between the plasma antioxidant status and different motor features indicates that the antioxidant mechanisms underlying tremor and PIGD of PD may be different.     

Workshop III: late motor complications of Parkinson's disease

The aim in the current treatment of Parkinson's disease is to delay L-Dopa administration and to keep the L-Dopa dosage as low as possible. Such a treatment strategy can delay the onset of late motor complications and reduce their severity. L-Dopa remains the most potent anti-parkinsonian medication, but its use for the initial therapy of Parkinson's disease is limited to elderly patients. In all other cases, dopamine agonists, budipine, amantadine and selegiline are primarily used. With the occurrence of late motor complications continuous dopamine receptor stimulation becomes essential. In this situation, combination therapy has to be individualized, with dopamine agonists playing a key role. In addition, COMT inhibitors, budipine, amantadine and selegiline may be used. Anticholinergic drugs are of very limited importance in the current treatment of Parkinson's disease.     

Workshop III: Late motor complications of Parkinson's disease

Journal of Neurology - The aim in the current treatment of Parkinson's disease is to delay L-Dopa administration and to keep the L-Dopa dosage as low as possible. Such a treatment strategy can...     

Parkinson's disease motor subtypes and mood

Parkinson's disease is heterogeneous, both in terms of motor symptoms and mood. Identifying associations between phenotypic variants of motor and mood subtypes may provide clues to understand mechanisms underlying mood disorder and symptoms in Parkinson's disease. A total of 513 patients were assessed using the Hospital Anxiety and Depression Scale, and separately classified into anxious, depressed, and anxious-depressed mood classes based on latent class analysis of a semistructured interview. Motor subtypes assessed related to age-of-onset, rate of progression, presence of motor fluctuations, lateralization of motor symptoms, tremor dominance, and the presence of postural instability and gait symptoms and falls. The directions of observed associations tended to support previous findings with the exception of lateralization of symptoms, for which there were no consistent or significant results. Regression models examining a range of motor subtypes together indicated increased risk of anxiety in patients with younger age-of-onset and motor fluctuations. In contrast, depression was most strongly related to axial motor symptoms. Different risk factors were observed for depressed patients with and without anxiety, suggesting heterogeneity within Parkinson's disease depression. Such association data may suggest possible underlying common risk factors for motor subtype and mood. Combined with convergent evidence from other sources, possible mechanisms may include cholinergic system damage and white matter changes contributing to non-anxious depression in Parkinson's disease, while situational factors related to threat and unpredictability may contribute to the exacerbation and maintenance of anxiety in susceptible individuals.     

Nonmotor features of Parkinson's disease subtypes

Parkinson's disease is highly heterogeneous in early clinical features and later outcomes. This makes classifying subgroups of PD relevant to clinical research and practice, particularly if they are prognostically relevant. Subgroups have been defined both on the basis of motor and nonmotor features, and subgroups have been determined either empirically, based on clinical observation, or using data‐driven analytic techniques. Previous studies have examined both the overall number and the nature of nonmotor symptoms and signs in tremor‐dominant compared with non‐tremor‐dominant subtypes, and longitudinal studies identify nonmotor symptoms as important markers of prognosis and important defining features of PD subtypes. Autonomic features seem to preferentially affect individuals with non‐tremor‐dominant PD subtype early in the disease. Later in the disease cognitive disturbance distinguishes this phenotype. Pathological and neuroimaging studies provide substantial evidence for fundamental biological differences between tremor‐dominant and postural instability gait disorder/akinetic‐rigid subtypes. Biomarker studies point toward non‐tremor‐dominant PD as representing more advanced and diffuse neurodegeneration than tremor‐dominant PD, encompassing dopaminergic and nondopaminergic as well as synuclein and nonsynuclein (Abeta) pathologies. This aligns with clinical studies that find a higher burden of nonmotor symptoms in non‐tremor‐dominant PD. The mounting evidence for the relevance of nonmotor features in PD subtypes behooves us to begin to investigate the biological underpinnings of subtypes defined by both motor and nonmotor features. This may be challenging, as PD subtypes are unlikely to be distinct nonoverlapping entities but are more likely to represent typical phenotypes within a multidimensional spectrum resulting from variable contributions of a number of simultaneous pathological processes. © 2016 International Parkinson and Movement Disorder Society