Validity of spiral analysis in early Parkinson's disease

Spiral analysis is an objective, easy to administer noninvasive test that has been proposed to measure motor dysfunction in Parkinson disease (PD). We compared overall Unified Parkinson Disease Rating Scale Part III scores to selected indices derived from spiral analysis in seventy‐four patients with early PD (mean duration of disease 2.4 ± 1.7 years, mean age 61.5 ± 9.7 years). Of the spiral indices, degree of severity, first order zero crossing, second order smoothness, and mean speed were best correlated with total motor Unified Parkinson's Disease Rating Scale (UPDRS) score (all P < 0.01), and these indices showed a gradient across worsening tertiles of UPDRS (P < 0.05). Spiral indices also correlated with UPDRS ratings for the worst side and worst arm scores as well. The domains of bradykinesia, rigidity, and action tremor were correlated with first order crossing, second order smoothness, and mean speed, where as rest tremor was most highly correlated with degree of severity. This suggests that the spiral analysis may supplement motor assessment in PD, although further analysis of spiral metrics, a larger sample and longitudinal data should be evaluated. © 2007 Movement Disorder Society     

Unilateral caudal zona incerta deep brain stimulation for Parkinsonian tremor

BackgroundThe subthalamic nucleus is currently the target of choice in deep brain stimulation (DBS) for Parkinson's disease (PD), while thalamic DBS is used in some cases of tremor-dominant PD. Recently, a number of studies have presented promising results from DBS in the posterior subthalamic area, including the caudal zona incerta (cZi). The aim of the current study was to evaluate cZi DBS in tremor-dominant Parkinson's disease.Methods14 patients with predominately unilateral tremor-dominant PD and insufficient relief from pharmacologic therapy were included and evaluated according to the motor part of the Unified Parkinson Disease Rating Scale (UPDRS). The mean age was 65 ± 6.1 years and the disease duration 7 ± 5.7 years. Thirteen patients were operated on with unilateral cZi DBS and 1 patient with a bilateral staged procedure. Five patients had non-L-dopa responsive symptoms. The patients were evaluated on/off medication before surgery and on/off medication and stimulation after a minimum of 12 months after surgery.ResultsAt the follow-up after a mean of 18.1 months stimulation in the off-medication state improved the contralateral UPDRS III score by 47.7%. Contralateral tremor, rigidity, and bradykinesia were improved by 82.2%, 34.3%, and 26.7%, respectively. Stimulation alone abolished tremor at rest in 10 (66.7%) and action tremor in 8 (53.3%) of the patients.ConclusionUnilateral cZi DBS seems to be safe and effective for patients with severe Parkinsonian tremor. The effects on rigidity and bradykinesia were, however, not as profound as in previous reports of DBS in this area.     

不同运动功能障碍对帕金森病患者日常生活活动能力的影响

目的探讨影响帕金森病(PD)患者日常生活活动(ADL)的运动症状。方法 93例PD患者接受了调查。采用PD统一评分量表第2、3、4部分,分别评估患者的ADL、运动功能障碍和运动并发症。将帕金森病综合评分量表(UPDRS)运动评分分为6部分:震颤、肌强直、动作缓慢、面部表情、语言表达和中轴(步态和姿势)损伤。采用逐步线性回归来评估患者ADL与各具体运动功能障碍之间的相关性。结果中轴损伤是PD患者UPDRS II评分最主要的预测因子,语言表达、动作缓慢和震颤也有一定的预测作用。4项因素相加能够解释72%的UPDRS II评分变化。结论 PD治疗过程中应重视患者的中轴运动损伤症状,加强康复治疗,以提高患者的ADL。     

Progression of parkinsonian signs in Parkinson disease

BACKGROUND: Current knowledge about the rate of progression of extrapyramidal signs (EPSs) in Parkinson disease (PD) is derived largely from cross-sectional studies comparing subjects at various stages of illness rather than longitudinal studies in which the subjects were followed up over time. OBJECTIVE: To longitudinally study the progression of EPSs in PD by quantifying the rate of change of EPSs and by examining each EPS (rigidity, bradykinesia, tremor, and postural instability) separately. METHODS: A community-based cohort of 237 patients with PD living in Washington Heights-Inwood in Manhattan, NY, was evaluated at baseline and at yearly intervals. The EPSs were rated using the motor portion of the Unified Parkinson's Disease Rating Scale Motor Examination. Analyses of longitudinal data were performed by applying generalized estimating equations to regression analyses. RESULTS: The total EPS score increased at an annual rate of 1.5 points (1.5%), but, among those who died, the total EPS score increased at an annual rate of 3.6 points (3.6%). Bradykinesia, rigidity, and gait and balance subscores worsened at similar annual rates of 2.0% to 3.1%, whereas the tremor subscore did not clearly worsen with time. Patients with a shorter disease duration (< or =3 years) may have progressed more rapidly than patients with longer disease duration (annual rate of change, 1.9% vs 1.4%, respectively), although this did not reach statistical significance. A high total EPS score was independently associated with dementia, low Activities of Daily Living score, and long disease duration at baseline. CONCLUSIONS: In this cohort, the progression of EPSs in PD occurred at a rate of 1.5% per year and at twice that rate among those who died. Bradykinesia, rigidity, and gait and balance impairment worsened at similar rates, whereas tremor did not, suggesting that tremor may be relatively independent of these other cardinal manifestations of PD.     

Efficacy of dance for Parkinson’s disease: a pooled analysis of 372 patients

Journal of Neurology - Parkinson’s disease (PD) is a neurodegenerative disorder that presents with motor and nonmotor symptoms such as bradykinesia, resting tremor, postural instability, and...     

Factors related to clinically probable REM sleep behavior disorder in Parkinson disease

Rapid eye movement sleep behavior disorder (RBD) is commonly accompanied in Parkinson disease (PD). However, the underlying mechanism linking RBD to PD remains unclear. We interviewed and examined 447 consecutive patients with PD to investigate factors associated with the presence of RBD in PD patients. Using the minimal diagnostic criteria for parasomnias provided in the International Classification of Sleep Disorders-Revised (ICSD-R), 164 patients (36.5%) were diagnosed with clinically probable RBD (cpRBD). PD patients with cpRBD were older, had a longer duration of PD, a more severe level of disability, a longer duration of antiparkinsonian medication, and a lower proportion of their Unified Parkinson Disease Rating Scale (UPDRS) scores accounted for by tremor than those without RBD. Multivariate and univariate logistic regression analyses revealed that patient age, PD symptom duration (and, accordingly, more severe motor disability), tremor score, and proportion of the UPDRS score accounted for by tremor were significant factors associated with the presence of RBD in PD patients. The results of the present study support previous observations that PD with RBD may result from a different underlying pattern of neurodegeneration than PD without RBD.     

Cerebrospinal Fluid C-Reactive Protein in Parkinson’s Disease: Associations with Motor and Non-motor Symptoms

Parkinson’ disease (PD) is characterized by motor symptoms including bradykinesia, resting tremor, postural instability, and rigidity and non-motor symptoms such as cognitive impairment, sleep disorder, and depression. Neuroinflammation has been recently implicated in pathophysiology of both motor and non-motor symptoms of PD. One of the most notable inflammatory proteins is C-reactive protein (CRP), which is elevated in the conditions of systemic inflammation. Using BioFIND database, we scrutinized the possible association between cerebrospinal fluid (CSF) levels of CRP and severity of PD motor and non-motor symptoms. Eighty-four healthy controls (HCs) and 109 PD subjects were entered into this study. A significant correlation was observed between CSF CRP levels and Movement Disorder Society-Unified Parkinson’s Disease Rating Scale Part III (MDS-UPDRS part III) score and Montreal Cognitive Assessment (MoCA) score in PD patients. We found significant correlations between MoCA score and CSF CRP levels in female patients and between CSF CRP and MDS-UPDRS part III score and MoCA score in male patients. In linear regression, CSF CRP could predict 6.9 and 10% of changes in MDS-UPDRS part III score in all PD patients male PD patients, respectively. In summary, we confirmed that CSF concentrations of CRP are in correlation with motor and non-motor severity in PD subjects. Our findings suggest that neuroinflammation plays an important role in the initiation and probably progression of PD motor and non-motor symptoms, which may give us a better insight into the underlying pathologic mechanisms in PD.     

Family history of hand tremor in patients with early Parkinson’s disease

Some patients with Parkinson’s disease (PD) report hand tremors in their relatives. This study aimed to compare the clinical characteristics of early PD in patients with and without a family history of hand tremor. This study included 337 early and drug-naïve patients with PD. The family history of hand tremor was obtained from the patients and their caregivers. Motor and non-motor symptoms of PD were assessed using the appropriate scales. A family history of hand tremor was present in 27 of 337 patients with PD (8.0%). Patients with a family history of hand tremor had significantly higher scores for rest tremors than those without. No significant differences were found in action tremor, bradykinesia, rigidity, gait, or posture scores between the two groups. The proportion of tremor-dominant subtypes was higher in patients with a family history of hand tremor than in those without (51.8% vs. 28.7%). Patients with PD, with a family history of hand tremor, had significantly lower scores in the urinary and sexual subdomains of the Non-Motor Symptoms Scale for PD than in those without. A family history of hand tremor affects the motor and non-motor symptoms in patients with early PD. It is necessary to investigate the family history of hand tremor in patients with PD.     

Contribution of aging to the severity of different motor signs in Parkinson disease

BACKGROUND: Evidence does not support the view that Parkinson disease (PD) represents an accelerated aging process; however, the additional contribution of aging to the severity of different motor signs in patients with PD is not known. This knowledge may have implications for clinical trials of neuroprotective agents in PD. OBJECTIVE: To investigate the contribution of aging to the severity of the different motor signs of idiopathic PD. SETTING: Center for Parkinson Disease and Other Movement Disorders of the Columbia University Medical Center and a neurology clinic that primarily served individuals from the Washington Heights-Inwood community in New York City. PATIENTS: Sample of patients with a wide range of disease duration and age. DESIGN: Cross-sectional clinic-based study. Patients with PD were evaluated using the Unified Parkinson Disease Rating Scale (UPDRS). The total UPDRS motor score was divided into 6 motor domains (tremor, rigidity, bradykinesia, facial expression, speech, and axial impairment) and 2 subscores that represented predominantly dopaminergic (subscore A: tremor, rigidity, bradykinesia, and facial expression) and nondopaminergic (subscore B: speech and axial impairment) deficiency. Analyses were performed using linear regression models with the UPDRS motor domains and subscores as the outcomes. The variation (adjusted R(2)) of the outcome variables explained by the inclusion of disease duration in the models, adjusting for sex, years of education, levodopa dosage, and use of other antiparkinsonian medications, was calculated. The additional variation explained by adding age at examination to the models was used to gauge the contribution of aging to each motor domain and subscore of the UPDRS. RESULTS: A total of 451 patients participated in the study. Mean age at examination was 62.0 years (SD, 12.6 years; median, 62.0 years; range, 18-93 years), and mean disease duration was 7.2 years (SD, 5.9 years; median, 5.6 years; range, 0.1-41.6 years). The additional variation of the outcome variable explained by including age in the models was higher for subscore B (14.3%; 95% confidence interval [CI], 9.9%-20.4%) than subscore A (4.7%; 95% CI, 2.0%-9.1%). Among the 6 motor domains, the additional variation of the outcome variable explained by including age in the models was highest for axial impairment (13.6%; 95% CI, 9.4%-19.6%). CONCLUSION: Axial (gait and postural) impairment in PD may result from the combined effect of the disease and the aging process on nondopaminergic subcortical structures.     

Application of the Unified Parkinson's Disease Rating Scale in progressive supranuclear palsy: factor analysis of the motor scale.

An important criterion in scale validation is the demonstration of a stable factor structure. The Unified Parkinson's Disease Rating Scale (UPDRS) is widely used to assess Parkinson's disease (PD). The reliability and applicability of the motor subscale of the UPDRS (UPDRSm) when applied to patients diagnosed with progressive supranuclear palsy (PSP) is unknown. In a sample of 175 patients with PSP, factor analysis revealed five clinically distinct factors: two independent bradykinesia factors (axial/gait and extremities), one rigidity factor, and two independent tremor factors (rest and action). Two items (posture and rest head tremor) did not reach criteria for factor loadings. There was a high degree of internal consistency. These results suggest that UPDRSm is a reliable and applicable scale for assessing most aspects of PSP function as well as severity measures of five clinical disability domains.     

Freezing of gait in PD: prospective assessment in the DATATOP cohort.

OBJECTIVE: To study the development of freezing of gait in PD. BACKGROUND: Freezing of gait is a common, disabling, and poorly understood symptom in PD. METHODS: The authors analyzed data from 800 patients with early PD from the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) clinical trial who were assigned either placebo, deprenyl, tocopherol, or the combination of deprenyl and tocopherol. The primary outcome measure was the time from randomization until the freezing of gait score on the Unified Parkinson's Disease Rating Scale (UPDRS) became positive. RESULTS: Fifty-seven patients (7.1%) had freezing of gait at study entry and 193 (26%) of the remaining patients experienced the symptom by the end of the follow-up period. Those with freezing of gait at baseline had significantly more advanced disease than those without the symptom, as measured by total UPDRS and Hoehn and Yahr stage. High baseline risk factors for developing freezing of gait during the follow-up period were the onset of PD with a gait disorder; higher scores of rigidity, postural instability, bradykinesia and speech; and longer disease duration. In contrast, tremor was strongly associated with a decreased risk for freezing of gait. At the end of follow-up, the signs most strongly associated with the freezing phenomenon were gait, balance, and speech disorders, not rigidity or bradykinesia. Deprenyl treatment was strongly associated with a decreased risk for developing freezing of gait; tocopherol had no effect. CONCLUSIONS: Freezing of gait is directly related to duration of PD. Risk factors at onset of disease are the absence of tremor and PD beginning as a gait disorder. The development of freezing of gait in the course of the illness is strongly associated with the development of balance and speech problems, less so with the worsening of bradykinesia, and is not associated with the progression of rigidity. These results support the concept that the freezing phenomenon is distinct from bradykinesia. Deprenyl, in the absence of L-dopa, was found to be an effective prophylactic treatment and should be considered for patients with PD who have an onset of gait difficulty.     

Thalamic stimulation alleviates levodopa-resistant rigidity in a patient with non-Parkinson’s disease parkinsonian syndrome

Deep brain stimulation (DBS) to the thalamic ventrointermediate nucleus (Vim) is a useful treatment in patients with tremor-dominant Parkinson’s disease (PD). Efficacy to alleviate rigidity remains controversial. We report a 65-year-old right-handed man with persistent severe rigidity and bradykinesia on the right side despite daily administration of levodopa/carbidopa (600/60 mg). His right-hand tremor was continuous at rest and present at action. His antiparkinsonian medications appeared ineffective and he reported difficulties with writing and eating. Repeated ¹²³I-meta-iodobenzylguanidine myocardial scintigraphy studies demonstrated a non-PD pattern. He underwent the stereotactic implantation of a DBS electrode into the left Vim. Using contacts 1 and 2 we started continuous unipolar stimulation with a pulse generator implanted in a subclavian pocket. This improved the tremor and the rigidity and bradykinesia of his right hand. Postoperative image analysis revealed the likelihood of simultaneous stimulation of the Vim and the nucleus ventralis oralis posterior. Our findings suggest thalamic stimulation as a therapeutic option for drug-resistant rigidity (and tremor) in patients with parkinsonian syndromes ineligible for DBS targeted at the globus pallidus internus or subthalamic nucleus.     

Comparison of extrapyramidal signs in dementia with Lewy bodies and Parkinson's disease

Extrapyramidal signs (EPS) were compared in 98 dementia with Lewy bodies (DLB) and 130 medication-responsive Parkinson's disease (PD) patients. DLB patients were older at assessment and at disease onset, were cognitively more impaired, and had a shorter duration of disease than PD patients. Sixty-seven DLB patients (68%) showed EPS. The 58 DLB patients with complete data had more severe action tremor, body bradykinesia, difficulty arising from a chair, and facial expression, gait, and rigidity symptoms than PD patients (all P<0.001). Abnormal posture and tremor at rest did not differ. Severity of EPS correlated with age, duration of disease, and cognitive impairment in PD patients but not in DLB patients. Studies of the clinical significance and management of EPS in DLB patients are needed.     

Benign tremulous Parkinson's disease

OBJECTIVE: To analyze the long-term outcomes of patients presenting with pure parkinsonian tremor and to determine whether or not such patients develop the other features of Parkinson's disease (PD) eventually. METHODS AND MATERIALS: Two hundred fifty-one patients with PD followed at our referral center were examined regularly. In this study, we evaluated the long-term follow up of the the patients with parkinsonian tremor without bradykinesia or rigidity. RESULTS: The mean disease duration was 5 years (range: 2-10 yrs.) at the last follow-up visit. This final group included 7 female and 16 male patients with a mean age of 66.6 +/- 10.8 years. Four groups of patients were identified. First group consisted of 15 patients presenting with rest tremor; most prominently in one upper limb and/or contra-lateral upper limb. In the second group, there were 3 patients who had parkinsonian tremor with greatest severity in one lower limb and ipsilateral upper limb. Group 3 comprised 2 patients who had parkinsonian tremor in only one lower limb. The fourth group comprised 3 patients with isolated jaw tremor. CONCLUSIONS: Some patients with pure parkinsonian tremor may remain without bradykinesia or rigidity for a long time, which may be considered a benign form of Parkinson's disease.     

Cognitive and motor function in patients with Parkinson's disease with and without depression

The objective of this study was to define risk factors for depression in patients with idiopathic Parkinson's disease (PD) and to evaluate the correlation of depression with cognitive function and the primary domains of parkinsonian motor dysfunction tremor, bradykinesia, rigidity, gait and balance impairment. The risk factors for depression in patients with PD remain controversial. Several investigators have demonstrated a significant association between cognitive dysfunction and depression, but motoric and disease variables can confound this evaluation and have shown an inconsistent relation to depression. A consecutive series of 88 patients with PD were examined using the motor subscale of the Unified Parkinson's Disease Rating Scale (UPDRSm), Hoehn-Yahr stage (HY), and Hamilton Rating Scale for Depression (HRSD). Major depression was diagnosed according to the criteria in the Diagnostic and Statistic Manual of Mental Disorders, 4th edition. Gender, age, handedness, PD duration, side of PD onset, motor fluctuations, UPDRSm total score, daily Levodopa dose, and Mini-Mental State Examination score (MMSE) were analyzed using multivariate and univariate logistic regression, Fisher's Exact test, and Pearson correlations. Major depression was diagnosed in 12 patients (7.3%). Low MMSE score, axial bradykinesia, gait and balance impairment were strongly significant predictors of depression. In conclusion, depression and physical function are important factors impairing the quality of life for patients with PD, and regular depression screening and treatment should focus on patients with PD who have cognitive impairment, high axial bradykinesia, gait and balance impairment.     

Diagnosing Parkinson's disease using videotaped neurological examinations: validity and factors that contribute to incorrect diagnoses.

Field work is commonly required in movement disorders research. Sending neurologists into the field can be logistically challenging and costly. Alternatively, neurological examinations may be videotaped and reviewed later. There is little knowledge of the validity of the videotaped neurological examination in the diagnosis of Parkinson's disease (PD). We examined the validity of the videotaped Unified Parkinson's Disease Rating Scale (UPDRS) motor examination in the diagnosis of PD, and sought to determine which factors are associated with incorrect diagnoses. PD patients and controls were enrolled in a familial aggregation study between August of 1998 and June of 2000, and as part of that study each was examined by a physician who performed an in-person UPDRS motor examination. Each also underwent a second, videotaped UPDRS motor examination. Based on the review of this videotape, a neurologist, who was blinded to the previous clinical diagnosis, assigned a diagnosis of PD or normal. A total of 211 of 231 PD patients (sensitivity = 91.3%), and 170 of 172 controls (specificity = 98.8%) were correctly identified based on the videotape. True positives had a higher mean rest tremor score (1.7 vs. 0.3; P < 0.001), action tremor score (0.9 vs. 0.3; P < 0.001), bradykinesia score (11.2 vs. 7.4; P = 0.02), and disease of longer mean duration (8.9 vs. 5.8 years; P = 0.001) than false negatives. False negatives did not differ from true positives in terms of age, total dose of levodopa, Hoehn and Yahr score, or rigidity, gait and posture, or facial masking scores (each assessed during the in-person examination). The videotaped UPDRS motor examination is a useful means of diagnosing PD and provides an alternative approach for the diagnosis of PD in field studies. A limitation is that patients with milder PD of shorter duration may not be recognized as PD.     

Factors predicting response to dopaminergic treatment for resting tremor of Parkinson's disease

We aimed to evaluate the clinical factors predicting response to dopaminergic treatment for resting tremor in patients with Parkinson's disease (PD). Eighty‐five PD patients with prominent resting tremor, defined as tremors of score greater than 3 in at least one limb on the Unified Parkinson's Disease Rating Scale (UPDRS), were divided into those responsive or nonresponsive to dopaminergic treatment. Responsiveness was defined as a reduction of at least two points for more than 3 months in the UPDRS tremor score. Of the 85 patients, 36 (42.4%) were responsive and 49 (57.6%) were nonresponsive to dopaminergic treatment. Initial UPDRS III score (P = 0.015) and Hoehn and Yahr stage (P = 0.010) were each significantly higher in the RG than in the NRG. UPDRS subscores for rigidity (P = 0.012), bradykinesia (P = 0.021) and postural impairment (P = 0.018) also correlated with responsiveness to dopaminergic treatment. Resting tremor in PD patients was more responsive to dopaminergic treatment when accompanied by moderate degrees of bradykinesia and rigidity than in patients without other prominent parkinsonian features. © 2007 Movement Disorder Society     

Premotor symptoms and early diagnosis of Parkinson's disease

Parkinson's disease is a disorder characterized by the motor findings of bradykinesia, rest tremor, cogwheel rigidity, and postural instability. As the disease progresses, most patients develop numerous nonmotor signs and symptoms, many of which play a major role in reducing quality of life. What is becoming increasingly clear is that nonmotor findings, including hyposmia, sleep disorders, autonomic abnormalities, cognitive changes, and neurobehavioral changes, often precede the motor findings.     

Gaucher's disease with Parkinson's disease: clinical and pathological aspects

The association between type 1 Gaucher disease and PD has been reported in the literature. The clinical picture is characterized by the predominance of bilateral akinetic-rigid signs and poor response to levodopa therapy. The authors describe four patients (two siblings) with type 1 Gaucher disease presenting with the following signs of typical PD: asymmetric onset of rigidity, resting tremor, bradykinesia, and a favorable response to Parkinson therapies.     

Factor structure of parkinsonian signs in the community-dwelling elderly.

Parkinsonian signs are present in 40% of older people. Factor analysis of the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS) in patients with Parkinson's disease (PD) has identified several principal domains, including rigidity, axial function, and rest tremor. We hypothesized that if Parkinsonian signs in the elderly were due to basal ganglia dysfunction that this same constellation of factors (rigidity, axial function, rest tremor) would emerge in a factor analysis. We carried out factor analysis, using the principal component method with orthogonal (varimax) rotation, on motor UPDRS scores in community-dwelling elderly without PD. A modified (10-item) version of the motor portion of the UPDRS was administered to 1,339 older adults living in the Washington Heights-Inwood community and it was found that Parkinsonian signs were present in 537 (40.1%). Three factors (rigidity, axial function. and rest tremor) were obtained from the factor analysis and, together, explained 67.4% of the variance. A second factor analysis was carried out excluding the 26 participants with rest tremor, and two factors (rigidity, axial function) emerged. These data support the view that Parkinsonian signs in older adults might be due to basal ganglia dysfunction, a possibility that requires further exploration.