Parkinson disease patient with fibromyalgia: a case report

Parkinson's disease (PD) is characterized by motor disturbances such as tremor, slow movement and rigidity. Also, pain is a common symptom in patients with PD. The prevalence of pain is 40-75% in patients with PD. Physicians should pay attention to pain in patient with PD. We report a PD patient who suffered from fibromyalgia (FM). If the amount of pain is not maximal in the side more affected by parkinsonism and pain is not markedly relieved when the patient is in the "on" state, the pain may be due to FM.     

Pain in Parkinson's disease and multiple sclerosis: its relation to the medial and lateral pain systems

Although pain is one of the major clinical symptoms of Parkinson's disease (PD) and multiple sclerosis (MS), it is often neglected and therefore undertreated. The question why the perception of pain in stages without cognitive impairment is not affected by the neuropathology has not been addressed so far. Furthermore, changes in the experience of pain as a result of cognitive impairment have not been clinically studied in PD and MS. These issues which are very relevant for pain assessment and treatment, will be addressed by discussing the neuropathology in the medial and lateral pain systems in cognitively intact versus cognitively impaired patients with PD and MS. Since there are no clinical studies that specifically address pain in cognitively impaired PD and MS patients, hypotheses will be generated about the impact of cognitive impairment on pain experience in these patients. These hypotheses should be a challenge for new research in this important but neglected area.     

Radicular and nonradicular back pain in Parkinson's disease: a controlled study.

Postural abnormalities and increased muscle tone in Parkinson's disease (PD) may cause back pain. In this controlled study, we analyzed features of back pain in PD patients. The prevalence of back pain was 74% in PD patients (n = 101) when compared with 27% in control patients (n = 132; P < 0.0001, fisher's exact test), but did not correlate with disease severity or duration. The mean back pain intensity (visual analog scale of 0-10) was 4.3 for PD patients, and 1.3 for controls. Both radicular and nonradicular types of back pain were more frequent, and back pain caused more impairment in PD patients. However, it is noteworthy that the PD patients in our study did not receive more pain medication than control patients. This suggests that back pain in PD patients is often neglected and insufficiently treated. Our results argue for the routine evaluation of back pain in every patient suffering from PD.     

Pattern of subclinical pulmonary dysfunctions in Parkinson's disease and the effect of levodopa.

We performed a detailed evaluation of pulmonary function in 53 patients with idiopathic Parkinson's disease (PD) who did not have symptoms of pulmonary or cardiac dysfunction. There was a significant pulmonary dysfunction of restrictive type which partially responded to levodopa. Compared to men, women were more severely affected. Pulmonary function assessment is recommended in PD, irrespective of severity of disease.     

Spontaneous pain, pain threshold, and pain tolerance in Parkinson��s disease

The mechanisms underlying pain in Parkinson's disease (PD) are unclear. Although a few studies have reported that PD patients may have low pain threshold and tolerance, none could accurately assess whether there was a correlation between sensory thresholds and demographic/clinical features of PD patients. Thus, tactile threshold, pain threshold, and pain tolerance to electrical stimuli in the hands and feet were assessed in 106 parkinsonian patients (of whom 66 reported chronic pain) and 51 age- and sex-matched healthy subjects. Linear regression models determined relationships between psychophysical parameters and demographic/clinical features. Female gender, severity of disease, medical disease associated with painful symptoms, and dyskinesia were more frequently observed in PD patients experiencing pain, even though dyskinesia did not reach significance. Pain threshold and pain tolerance were significantly lower in PD patients than in control subjects, whereas the tactile threshold yielded comparable values in both groups. Multivariable linear regression analyses yielded significant inverse correlations of pain threshold and pain tolerance with motor symptom severity and Beck depression inventory. Pain threshold and pain tolerance did not differ between PD patients with and without pain. In the former group, there was no relationship between pain threshold and the intensity/type of pain, and number of painful body parts. These findings suggest that pain threshold and pain tolerance tend to decrease as PD progresses, which can predispose to pain development. Female gender, dyskinesia, medical conditions associated with painful symptoms, and postural abnormalities secondary to rigidity/bradikinesia may contribute to the appearance of spontaneous pain in predisposed subjects.     

Quality of life and pain in Parkinson's disease: a controlled cross-sectional study

PURPOSE: To compare health-related quality of life (HRQL) and pain symptoms in patients with PD with a matched control group. To our knowledge, controlled studies of Parkinson's disease (PD) patients within this area are rare. SCOPE: Fifty-seven patients and 95 controls took part in a self-administered questionnaire study. The instruments were the SF-36, visual analogue scales, pain drawing and pain-specific questions. CONCLUSIONS: Pain problems are common in PD patients but also to a large extent in the normal population. HRQL was reduced (p < or = 0.001) for the PD patients on all the scales on the SF-36 and consequently also in the pain dimension. The study indicates that even PD patients, who are optimally diagnosed and treated by a neurologist, might require additional rehabilitation treatment to improve their HRQL and pain problems.     

帕金森病~(99m)Tc-TRODAT-1多巴胺转运体SPECT初步临床应用研究

目的:评价多巴胺转运体(DTA)显象剂99mTc-2β-[N,N′-双(2-巯乙基)乙撑二氨基]甲基,3β(4-氯苯基)托烷(99mTc-TRODAT-1)诊断帕金森病(PD)及其严重程度(H/Y分级)相关性。方法:PD患者29例(H/Y1-4级),正常对照组22例,静脉注射99mTc-TRODAT-1,2-3hr后行DATSPECT显像,并应用ROI技术计算纹状体/小脑放射性比值(ST/CB),研究ST/CB与H/Y分级的相关性。结果:与正常对照组比较,PD患者纹状体内99mTc-TRODAT-1积聚显著下降,尤以壳核更为明显。早期PD患者(H/Y:1)不仅有病侧肢体对侧纹状体放射性分布减少,同侧纹状体放射性分布也明显减少,但对侧更明显,两侧壳核/小脑放射性比值有显著差异(P<0.05=。ST/CB与PD)的严程度重)(H/Y分级)无显著相关性。结论:99mTc-TRODAT-1DATSPECT显像有助于了解PD患者纹状体内突触前膜的DAT丢失情况,PD患者DAT明显减少,对PD的早期诊断及鉴别诊断有非常重要的意义。     

Prevalence of pain in Parkinson's disease: a systematic review using the modified QUADAS tool

Pain has been studied more intensely as a symptom of Parkinson's disease (PD) in recent years. However, studies on the characteristics and prevalence of pain in PD have yielded conflicting results, prompting us to do a systematic review of the literature. A systematic review of the literature was conducted, using different databases. The last inclusion date was March 15, 2011. The modified Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool was used, which is especially designed for judging prevalence studies on their methodological quality. Only articles that met the predefined criteria were used in this review. We found 18 articles, of which only 8 met the methodological criteria. Prevalence frequency ranges from 40% to 85% with a mean of 67.6%. Pain is most frequently located in the lower limbs, with almost one-half of all PD patients complaining about musculoskeletal pain (46.4%). The pain fluctuates with on-off periods. Surprisingly, only 52.4% of PD patients with pain used analgesics, most often nonopioids. PD patients seem to be predisposed to develop pain and physicians should be aware of pain as a common feature of PD. As many as one-half of PD patients with pain may be missing out on a potentially useful treatment, and proper treatment could increase quality of life in PD patients.     

Pain in Parkinson disease: A review of the literature

Parkinson's disease (PD) is a degenerative neurological disease presenting with motor and non-motor signs and symptoms. Approximately 30–50% of the patients experience pain. There is no consensus regarding the mechanisms and classification of pain in PD. This paper reviews current data on the possible mechanisms, classifications, evaluation and potential risk factors for pain in PD. Literature searches were performed to identify clinical trials and reviews covering patho-physiology, classification, type, evaluation and risk factors associated with pain in PD. Pain in PD could be related to pathologic changes in the anatomic structures involved in nociceptive mechanisms. Studies on pain mechanisms have been mostly conducted in animals. The mechanism of pain is complicated and influenced by different factors. There are several methodological differences between the studies trying to classify pain and to characterize its subtypes. Potential risk factors for pain in PD include: age, gender, and duration of the disease. Although pain is one of the non-motor symptoms most frequency experienced by patients, it is often under recognized and inadequately treated in contrast to motor symptoms Multicenter studies are needed that include a large cohort of subjects evaluated in multiple dimensions including pain in order to obtain more data and to allow improved management of pain in patients with PD.     

Chronic pain in Parkinson's disease: The cross‐sectional French DoPaMiP survey

Pain is a frequent, but poorly studied symptom of Parkinson's disease (PD). DoPaMiP survey aimed to assess the prevalence of chronic pain in PD, to describe PD patients with chronic pain, and to record analgesic consumption. About 450 parkinsonian patients underwent structured standardized clinical examination and completed self‐reported questionnaires in a cross sectional survey. Pains related or unrelated to PD were identified according to predefined criteria. About 98 patients with other chronic disorders than PD were examined to assess if pain was more frequent in PD than in this population. Two thirds parkinsonian patients (278 of 450) had chronic pain. Twenty‐five patients with non‐chronic pain (<3‐month duration) were excluded from subsequent analysis. Twenty six percent (111 of 425) parkinsonian patients had pain unrelated to PD (“non‐PD‐pain”, caused mainly by osteoarthritis), while 39.3% (167 of 425) had chronic pain related to PD (“PD‐pain”). In this last group, PD was the sole cause of pain in 103 and indirectly aggravated pain of another origin (mainly osteoarthritis) in 64. Parkinsonian patients with “PD‐pain” were younger at PD onset, had more motor complications, more severe depressive symptoms than those without pain or with “non‐PD pain.” “PD‐pain” was more intense (P = 0.03), but was less frequently reported to doctors (P = 0.02), and was associated with less frequent analgesic consumption than “non‐PD‐pain.” Pain was twice more frequent in PD patients than in patients without PD after adjustment for osteo‐articular comorbidities (OR = 1.9; 95% CI 1.2–3.2). Chronic pain is frequent but underreported in PD. Awareness of this problem should be increased and the assessment of analgesic strategies improved. © 2008 Movement Disorder Society     

Etiology and pathogenesis of Parkinson's disease: from mitochondrial dysfunctions to familial Parkinson's disease]

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. It is urgently needed to elucidate the cause of the disease and to establish neuroprotective treatment. We have been working on the etiology and pathogenesis of PD for many years and we found selective loss of mitochondrial complex I and the alpha-ketoglutarate dehydrogenase complex in the nigral neurons of patients with PD. Our observation firmly established mitochondrial defects in PD. Mitochondrial respiratory failure induces oxidative damage in neurons, and we found increase in hydroxynonenal and 8-oxo-deoxyguanine, indices of oxidative damage, in the nigral neurons of PD. These abnormalities can trigger apoptotic cell death. The primary events which induce mitochondrial failure and oxidative damage are not known, however, it has been postulated that the interaction of genetic risk factors and environmental factors would initiate the degenerative process. Based on this assumption, we conducted genetic association studies by the candidate gene methods. We found that polymorphic mutations of superoxide dismutase-2 and 24-kDa subunit of mitochondrial complex I were associated increased risk of developing Parkinson's disease. While we were doing this genetic association study, we found a family, in which parkinsonian phenotype completely segregated with a polymorphic mutation of the superoxide dismutase-2 gene. In this family, 4 out of 6 siblings were affected with early onset parkinsonism and the parents were apparently normal. Thus the mode of inheritance appeared to be autosomal recessive and this type is now called as AR-JP or Park2. We confirmed the linkage of this type of familial Parkinson's disease to the superoxide dismutase loci that is located in the telomeric region of chromosome 6 by the linkage analysis using microsatellite markers in this region. Then we found another family, in which an affected patient showed lack of one of the microsatellite markers (D6S315), which we were using in the linkage analysis. This observation prompted us to initiate the molecular cloning of the disease gene utilizing D6S315 as the initial probe. The molecular cloning was done with the collaboration with Professor Nobuyoshi Shimizu of Keio University. We identified a novel gene and confirmed that mutations of this novel gene were found only in the patients with autosomal recessive Parkinson's disease. The novel gene was named parkin. We conducted mutational analysis on more than 700 families with Parkinson's disease. We also established a method to detect compound heterozygotes of parkin mutations. Mutinous of the parkin gene were found in approximately 50% of autosomal recessive families. Many kinds of exonic deletions and point mutations were found. This type of familial Parkinson's disease had been considered to be unique among Japanese, but since we started mutational analysis of the parkin gene, we confirmed the world wide distribution of parkin gene mutations. Then we analyzed functions of parkin protein with the collaboration with Dr. Keiji Tanaka of Tokyo Metropolitan Institute of Medical Sciences. We found that parkin protein was a ubiquitin-protein ligase of the ubiquitin system. Now we are working on the candidate substrates of parkin protein as a ubiquitin ligase. We found that CDCrel-1, a synaptic vesicle protein, was a candidate substrate of parkin protein. In addition, we found two additional candidate proteins, i.e., alpha-synuclein 22 and PAEL receptor, with the collaboration of Professor Denis Selkoe of Harvard Medical School and Dr. Ryosuke Takahashi of RIKEN, respectively. Accumulation of PAEL receptor in the endoplasmic reticulum causes endoplasmic reticulum stress and apoptotic cell death. We found evidence to indicate accumulation of PAEL receptor and the presence of endoplasmic reticulum stress in a patient with AR-JP (Park2). Thus our studies firmly established that a genetic defect of an enzyme in the ubiquitin-proteasome system induces selective nigral neuronal death. We indicated the important role of the ubiquitin-proteasome system in neurodegeneration in general. In many other neurodegenerative disorders, such as Alzheimer's disease, Huntington's disease, Machado-Joseph disease, dentatorubral-pallidoluysian atrophy, and ALS, ubiquitinated proteins are accumulated in neurons. Thus protein handling in the ubiquitin-proteasome system appears to be affected in these neurodegenerative disorders despite the difference in the primary defects. Our studies also suggest many potential approaches for the discovery of neuroprotective treatment for not only Parkinson's disease but also other neurodegenerative disorders.     

Apathy: a complex symptom specific to the clinical pattern of presentation of Parkinson's disease?

There is currently no consensus on the nosological position of apathy in clinical practice, although many different articles indicate that apathy is a common, behavioral disturbance in the general Parkinson's disease (PD) population, often related to severe motor symptoms, hypothesizing that the dysfunction of the nigrostriatal pathway may play an important role in its pathophysiology. However, not all patients with PD become apathetic, indicating that apathy should not entirely be considered a dopamine-dependent syndrome in PD. The aim of this study was to examine the prevalence and clinical correlates of apathy in a representative community-based sample of patients within 2 variants of the PD: akinetic-rigid type and tremor-dominant type. Specifically, we wanted to investigate whether these 2 variants of PD would present with apathy as a primary behavioral disorder and whether apathy could be associated with different cognitive and behavioral disorders. Apathy is present in both the groups but significantly more evident in the akinetic-rigid group associated with frontal impairment but not related to motor impairment or depression. We discuss the results, starting with anatomical and physiological brain studies.     

Neurofilament M gene in a French-Canadian population with Parkinson's disease

BACKGROUND: Recently, a single base pair substitution (G1747A) mutation of the neurofilament M (NF-M) gene was reported in a French-Canadian patient with early onset Parkinson's disease (PD). Three unaffected siblings were found to be heterozygotes for the NF-M Gly336Ser mutation but, to date, no other affected PD individuals have been found with a similar mutation. No other individuals with Parkinson's disease and of similar ethnic background have been screened for this mutation. METHODS: We screened 102 French-Canadian patients with definite PD and 45 French-Canadian controls for this substitution in the NF-M gene using a PCR-restriction enzyme digestion method. RESULTS: None of the patients or controls carried this mutation. CONCLUSION: Our results would indicate that this mutation is not common even in a PD population of similar ethnic background and suggest this change represents a rare variant. However, these results do not exclude the possibility that other mutations in this gene could be present.     

The Threshold of Pain and Neurotransmitter's Change on Pain in Parkinson's Disease

Abstract: Among Parkinson's disease (PD) patients complaining of pain, 10 with pain not associated with a motor fluctuation or L-dopa therapy were evaluated. The controls were 14 PD without pain and eight with thalamic pain syndrome. The threshold of pain and neurotransmitters in CSF were measured in the three groups. In PD with pain, the maximum tolerance level and tourniquet pain ratio decreased significantly. In PD with pain, the score on the self-depression scale increased significantly and S-hydroxy-indole acetic acid (5-HIAA) among the neurotransmitters decreased significantly. These results suggest that decreases in the threshold of pain and changes of serotonin in CSF are involved in the development of specific pain in PD who do not respond to L-dopa.     

Pain in Parkinson's disease: analysis of 50 cases in a clinic of movement disorders

INTRODUCTION: Pain is a common symptom in Parkinson's disease (PD), and is often related to the illness itself. OBJECTIVE: To prospectively establish the occurrence of pain in PD patients. METHOD: This study was conducted within a population composed of 50 patients with PD to evaluate the presence of pain. RESULTS: Twenty-eight patients reported pain; comparing the group with pain and the group without pain, there were no differences related to the beginning of the illness and the motor symptoms of PD. However, many patients related an improvement of pain when antiparkinsonian therapy was initiated or adjusted. CONCLUSION: The use of techniques for analgesia and the adjustment of PD medication contribute to improve the manifestations of pain and the life quality of patients with PD.     

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.     

Analgesic action of methylphenidate on parkinsonian sensory symptoms. Mechanisms and pathophysiological implications

Intravenous administration of methylphenidate hydrochloride, a central stimulant, was unexpectedly found to exert a potent analgesic effect on primary sensory symptoms in a group of patients with Parkinson's disease. This effect, which has now been studied in a short-term, double-blind, placebo-controlled experiment, subsequently disappeared if patients were pretreated with a beta-blocker or with a serotonin antagonist. Cerebrospinal fluid monoamine metabolites were determined in some of these patients, and the 5-hydroxyindoleacetic acid level was found to be significantly lower than in parkinsonian patients without pain and in normal volunteers. Given the mechanism of action of methylphenidate on the central nervous system, the adrenergic and serotoninergic mediation of its analgesic effect, and the demonstration of impaired central serotonin metabolism in the patient group, it is concluded that not only central dopaminergic deficiency but also altered noradrenergic and serotoninergic transmission in the spinal cord are quite likely to play a role in the pathophysiology of pain in Parkinson's disease.     

Cognitive impairment in nondemented Parkinson's disease

A substantial percentage of patients with newly diagnosed Parkinson's disease without dementia are reported to be affected by cognitive impairment (CI). In practice, however, CI is underrecognized, as the signs may not be apparent in early-stage disease and many routine assessment tools lack the sensitivity to detect subtle cognitive dysfunction. Patients with PD and mild CI (MCI) may have a higher risk of developing dementia than cognitively intact PD patients; however, it is not currently known which patients with CI are at increased risk of developing dementia. This review summarizes current knowledge about CI in nondemented PD; it discusses the structural and functional changes associated with CI and addresses areas of unmet needs. We focus on questions that should be addressed in future studies to achieve consensus on its characteristics and definition, pathophysiology, epidemiology, diagnosis and assessment, and treatment and management.     

How common are complications of Parkinson's disease?

Background Parkinson's disease (PD) can be associated with a wide range of complications of advancing disease and treatment. However, it is unclear how often these occur in the overall population of patients with PD. Objective To assess the prevalence of disease and treatment complications and their clinical correlates in a community-based sample of 124 patients with PD. Results Average current age was 72 (SD 10.9) and mean disease duration 6 (SD 4.3) years. Falls with postural instability and other axial features were among the most common complications of advancing disease in this population (64 %). Motor fluctuations and dyskinesias affected approximately 30 and 20 % of the overall sample respectively, and changes in mental state such as dementia, depression and hallucinations each affected approximately one fifth of patients. Symptoms of autonomic nervous system dysfunction occurred in the great majority of patients, but were not associated with greater disease severity, disease duration or overall disability. Conclusion In contrast to clinic-based samples, the most frequently occurring complications of PD in this community-based sample were axial features such as postural instability with falls. These factors should be more taken into account in the allocation of health care resources and the treatment of symptoms of patients with PD in the community. Received: 31 January 2001, Received in revised form: 8 August 2001, Accepted: 21 August 2001