Continuous subcutaneous infusion of apomorphine for the treatment of Parkinson's disease

Apomorphine administered by subcutaneous infusion has been used efficiently in parkinsonian patients to treat severe motor fluctuations and levodopa-induced dyskinesias. Despite increasing evidence of its efficacy and its relative safety, apomorphine infusion therapy is still underused. This article reviews pharmacokinetic properties, efficacy, tolerability and indications of apomorphine infusion in Parkinson's disease.     

Advantages and limitations in the assessment of neuroprotective treatment of Parkinson's disease by functional imaging

INTRODUCTION: The development of neuroprotective strategies is a crucial issue for Parkinson's disease, since up to now only symptomatic therapies are available. The clinical evaluation of neuroprotective drugs is difficult considering the long-term effect of anti-Parkinsonian medication that nearly make impossible accurate measurement of the "true" clinical stage of the disease in the early years of progression. BACKGROUND: Two recent functional imaging studies (CALM-PD and REAL-PET) using positron emission tomography (PET) or single photon emission computed tomography (SPECT), suggest that dopamine agonist may have a neuroprotective effect compared to L-Dopa. CONCLUSION: These results are still controversial, notably because of the lack of clinical-imaging correlations, the absence of a placebo group and some important methodological considerations. Nevertheless, these studies are encouraging and give some arguments for the potential neuroprotective role of dopamine agonists. The aim of this work is first to present the pros and cons of these studies and second to propose guidelines in order to improve the design and methodology for future studies designed to assess the neuroprotective properties of new drugs in Parkinson's disease.     

Investigation of set-shifting ability in patients with Parkinson's disease: influence of task sequence type

INTRODUCTION: The aim of the present study was to investigate the origin of set-shifting deficits observed in Parkinson's disease (PD). METHODS: Seventeen patients diagnosed as having idiopathic PD were compared with 15 control subjects. We used a task-switching paradigm, including two tasks (task A and task B) so that subjects were required to switch either immediately after a switch-trial (i.e. alternating switch or ABA task sequence) or following one or two non-switch trials (ABBA or ABBBA task sequences). RESULTS: In both groups, switch cost (SC) in ABA task sequence was larger than SC in ABBA task sequence (p<0.05) and SC was larger in ABBA than ABBBA task sequence (p<0.05). PD patients demonstrated an increased SC compared to controls for alternating switch trials (p<0.01). Alternatively, when required to switch to a task abandoned two or three trials earlier (i.e. ABBA and ABBBA tasks sequences), patients did not demonstrate increased SC compared to controls. DISCUSSION AND CONCLUSION: The fact that SC associated with alternating switch trials was exacerbated in PD patients may reflect difficulties for switching to a recently inhibited task-set. In conclusion, our results indicate that set-shifting deficits in PD patients may depend of the type of task sequence.     

Parkinson's disease, progressive lumbar kyphosis and focal paraspinal myositis

INTRODUCTION: The camptocormia (bent spine) is characterized by a severe forward flexion of the thoracolumbar spine which disappears in the supine position. Clinical case. We describe a typical case observed in a parkinsonian patient. The MRI, electromyogram and biopsy of the paraspinal muscles revealed a typical myositis pattern. DISCUSSION: This case, the sixth published to our knowledge, confirms that focal myositis is associated with the camptocormia in Parkinson's disease. Typically it is observed in male subjects, appearing 4 to 6 years after the onset of Parkinson's disease, in fluctuating patients treated by an association of L-Dopa and agonist. It appears quickly and becomes the most important symptom. Antiparkinsonian drugs are useless. CONCLUSION: This exceptional picture raises original pathophysiological and therapeutic questions. Systematic studies should be performed in order to detail the pathophysiological link between these 3 entities: Parkinson's disease, focal myositis and camptocormia.     

Levodopa modifies pain thresholds in Parkinson's disease patients

OBJECTIVE: To assess levodopa dose effect on pain thresholds in Parkinson's disease (PD) patients using an experimental nociceptive thermal stimulation. PATIENTS AND METHODS: We evaluated pain thresholds in 20 PD patients treated by dopaminergic drugs. We assessed heat and cold pain thresholds by using 2 different methods (method of limits and method of levels), intensity-response curve and tolerance threshold. Each PD patient was evaluated in two conditions: ON (after administration of leovdopa and OFF (after acute levodopa withdrawal). The order was randomized. RESULTS: The mean age of patients was 652+/-9.9 years and the mean duration was 9.3+/-3.3 years. Heat pain thresholds were statistically higher in ON versus OFF condition using both methods (44.1+/-3,6 degrees C versus 42.3+/-3,1 degrees C, method of levels, p=0.02). Cold pain thresholds were statistically higher in ON versus OFF condition only using method of levels (17.9+/-4,4 degrees C versus 19.6+/-4,2 degrees C, p=0.02). Heat pain tolerance was statistically higher in ON versus OFF condition (21.4+/-21.6 seconds versus 14.7+/-20.3 seconds, p=0.02). CONCLUSION: This study showed that levodopa increased heat and cold pain thresholds and heat pain tolrance in PD patients. This suggests that dopaminergic drugs could have an analgesic effects on PD related pain.     

Perioperative management of Parkinson's disease

One of the particular characteristics of Parkinson's disease (PD) is the wide clinical variation as regards the treatment that can be found in the same patient. This occurs with specific treatment for PD, as well as with other drug groups that can make motor function worse. For this reason, the perioperative management of PD requires experience and above all appropriate planning. In this article, the peculiarities of PD and its treatment are reviewed, and a strategy is set out for the perioperative management of these patients.     

Pathophysiological mechanisms implicated by high-frequency stimulation in Parkinson's disease: the restoration of high and low frequency oscillatory systems

INTRODUCTION: Increased neuronal activity in the internal pallidum (GPi) and the subthalamic nucleus (STN) has been clearly demonstrated in Parkinsonian models, and the two structures have thus been selected as therapeutic targets for functional neurosurgery. High-frequency electrical stimulation of the GPi or the STN improves the parkinsonian symptoms but also dyskinesias directly by GPi stimulation or indirectly by reduction of L-Dopa associated with STN stimulation. According to Alexander's model of the organisation of the basal ganglia, electrical stimulation of GPi or STN should have led to uncontrolled hyperkinesia. This apparent paradox could be explained on one hand by the involvement of different anatomo-functional areas within these structures and on the other by spatial and temporal changes in neuronal discharge patterns in the basal ganglia which in turn produce variations in synchronisation. RESULTS: Event-related (de)synchronisation (ERD) has enabled us to study variations in subcortico-cortical oscillatory activity: it has been shown that high-frequency electrical stimulation of the GPi/STN increases desynchronisation of low frequency rhythms (mu and beta,<30 Hz) during movement preparation and execution and augments post-movement synchronisation. Stimulation also decreases the abnormal frontocentral spreading of desynchronisation during movement preparation. CONCLUSIONS: In accordance with previous coherence analyses, electrical stimulation of STN is likely to restore the activity of high-frequency and low-frequency systems, as evidenced by a decrease in the hypersynchronisation of low-frequency rhythms at rest and restoral of a high-frequency rhythm during movement. Stimulation may improve spatial selectivity by activating the selected programs in conjunction with the primary sensorimotor cortex, whilst inhibiting competitive programs represented by abnormal spreading outside the primary sensorimotor cortex.     

Survival in Parkinson's disease: the effect of dementia

In order to evaluate the effect of dementia on survival in Parkinson ’s disease (PD), we followed a series of 250 PD over a period of 5 years. Dementia was determined according to DSM-III-R criteria. Survival analysis of PD patients with dementia vs. without dementia was performed using entry date as starting point. Cox model was used for evaluation of variables associated with mortality in this sample. Upon inclusion to the study, dementia was diagnosed in 38% of our patients. At the end of the follow-up period, the cumulative death rates were 39% among the demented patients and 34% among the non-demented ones (χ²=3.2, df=1, p=0.07). Advanced age and, but marginally, cognitive deterioration were associated with reduced survival [Exp(β)=3.4, p=0.005 and Exp(β)=1.3, p=0.06, respectively].     

Krabbe病诊疗中国专家共识《Krabbe病诊疗中国专家共识》制订组

Krabbe病（KD）是一种罕见的常染色体隐性遗传性溶酶体贮积病,其病因为半乳糖脑苷脂酶的功能不足,导致半乳糖基鞘氨醇等有毒代谢产物在中枢和周围神经系统中积聚,引起神经脱髓鞘病变。KD在不同年龄段的发病特征和临床表现不同,其中婴儿型起病年龄早,病情进展快,常导致早期死亡。成人型表现出极大异质性,易于漏诊和误诊,给临床管理带来巨大挑战。为协助临床医生在KD的诊断和治疗中做出合理的决策,综合考虑国内外相关研究和指南,制定了适合我国具体情况的KD诊疗中国专家共识,旨在提高我国对KD的诊疗水平。 [国际神经病学神经外科学杂志, 2024, 51(2): 1-6]     

Clinical criteria for the switch of treatment strategies in Parkinson's disease

Along the years the treatment of Parkinson's disease with L-dopa has revealed unfavorable effects in general after 5–10 years. This has led to the present criteria for treatment of de novo patients that mainly relay on the age, the general strategy being to delay the use of L-dopa as long as possible. However, this practical approach lacks a scientific basis. In a retrospective study data of 155 patients with Parkinson's disease were analyzed with the goal of finding a clinical marker for the critical time point when L-dopa needs to be administrated. The clinical stage of the patients was assessed using the Hoehn and Yahr (H&Y) scale and the severity of the symptoms was measured using the UPDRS score. The results show that there was no relationship between the age of the patients and the therapy (L-dopa vs. no L-dopa) with regard to the clinical outcome. A significant interaction was found however, between the clinical stage (H&Y) and the therapy. Further analysis of this interaction showed that in the H&Y Stages 1–2.5 the UPDRS scores were lower in the patient groups treated without L-dopa. Remarkably, in the H&Y stages 3 and higher the UPDRS scores were lower in the patient groups treated with L-dopa. These results suggest that the clinical stage of the disease (H&Y) might be a better criterion than the age for the time point when L-dopa needs to be administered in de novo patients.     

Delivering patient-centered care in Parkinson's disease: Challenges and consensus from an international panel

An international panel of movement disorders specialists explored the views and perceptions of people with Parkinson's disease (PD) about their condition and its treatment, including the potential mismatch between the clinician's view of the patient's condition and their own view of what aspects of the disease most affect their daily lives. The initiative was focused on Asian countries, so participants comprised experts in the management of PD from key centers in Asia, with additional insight provided by European and the North American movement disorders experts. Analysis of peer-reviewed publications on patient perceptions of PD and the factors that they consider important to their wellbeing identified several contributing factors to the mismatch of views, including gaps in knowledge of PD and its treatment, an understanding of the clinical heterogeneity of PD, and the importance of a multidisciplinary approach to patient care. The faculty proposed options to bridge these gaps to ensure that PD patients receive the personalized treatment they need to achieve the best possible outcomes. It was considered essential to improve patient knowledge about PD and its treatment, as well as increasing the awareness of clinicians of PD heterogeneity in presentation and treatment response. A multidisciplinary and shared-care approach to PD was needed alongside the use of patient-centered outcome measures in clinical trials and clinical practice to better capture the patient experience and improve the delivery of individualized therapy.     

Discordance between measured postural instability and absence of clinical symptoms in Parkinson's disease patients in the early stages of the disease

We compared postural performances in early stage Parkinson's disease (PD) patients and healthy subjects, and to determine if PD patients have infraclinical postural instability. Nine PD patients and 18 age‐ and sex‐matched control subjects were recorded with open eyes (OE) and closed eyes (CE) using a force platform in static and dynamic conditions with a mobile platform allowing antero posterior and medio lateral oscillations. Oscillations of the mobile platform and balance strategy were quantified using both a force platform and the Vicon system. Under static conditions with both OE and CE, PD patients had a larger center foot pressure sway area than the control subjects (P = 0.007 and P = 0.04, respectively). Under dynamic conditions, the PD patients' sway area was greater than that of the control subjects in the CE antero posterior position (P = 0.04). Oscillations of the mobile platform were not different between the two groups. Lastly, all subjects used an ankle strategy, but PD patients had larger head oscillations than the control subjects. Early stage PD patients have an infraclinical postural instability which is compensated when it is more difficult to maintain good balance, suggesting that the neurological mechanisms of balance are partially still operating at this stage of the disease. © 2007 Movement Disorder Society     

Ropinirole for the treatment of tremor in early Parkinson's disease.

The effect of Ropinirole on tremor in early Parkinson's disease (PD) was assessed. The results of three multicentre, randomized, double-blind trials comparing ropinirole monotherapy with levodopa, bromocriptine and placebo treatment were analysed retrospectively with respect to improvement of resting tremor and postural/action tremor as measured by items 20 and 21 of the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS). Improvements in resting tremor were significantly better with ropinirole than placebo. There were no significant differences between the effect of ropinirole and those of levodopa (L-dopa) or bromocriptine on resting tremor. Postural/action tremor was mild in these early therapy studies, and there were no significant differences between treatment groups. These results suggest that ropinirole monotherapy is effective in treating resting tremor in early PD. On the other hand, response of postural/action tremor to dopaminergic treatment in early PD was not significantly better than to placebo at the dosages used in these trials.     

Prevalence, etiology, and treatment of depression in Parkinson's disease.

Parkinson's disease (PD) is primarily a disease of elderly individuals with a peak age at onset of 55 to 66 years. It is characterized by bradykinesia, rigidity, tremor, and postural instability; and affects approximately 1 million individuals in the US and is the second most common neurodegenerative disease next to Alzheimer's disease. The motor symptoms of PD are the focus of pharmacotherapy, yet the nonmotor symptoms (e.g., dementia, psychosis, anxiety, insomnia, autonomic dysfunction, and mood disturbances) can be the most disturbing, disabling, and misunderstood aspects of the disease. Depressive symptoms occur in approximately half of PD patients and are a significant cause of functional impairment for PD patients. There is accumulating evidence suggesting that depression in PD is secondary to the underlying neuroanatomical degeneration, rather than simply a reaction to the psychosocial stress and disability. The incidence of depression is correlated with changes in central serotonergic function and neurodegeneration of specific cortical and subcortical pathways. Understanding comorbid depression in PD may therefore add to the understanding of the neuroanatomical basis of melancholia.     

高度关注帕金森病非运动症状的早期识别与治疗

帕金森病以经典的四大运动症状,即静止性震颤、肌强直、运动迟缓和姿势平衡障碍为主要临床表现。根据帕金森病患者的症状主诉和临床医师的观察总结,发现在帕金森病患者经典运动症状外,还伴随诸多非运动症状,在疾病的发生发展过程中给患者带来较为严重的影响,加重运动障碍、缩短寿命、降低生活质量[1]。然而,Shulman等[2]认为,相对于运动症状,专科医师对帕金森病非运动症状的识别率和确诊率均低于50%。