Freezing of gait in postmortem-confirmed atypical parkinsonism.

The frequency and pathophysiology of freezing of gait (FoG) in atypical parkinsonism is unknown. We analysed the frequency of FoG in postmortem-confirmed atypical parkinsonian disorders (APD) comprising corticobasal degeneration (CBD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). Sixty-six patients with pathologically confirmed APD (CBD, n = 13; DLB, n = 14; MSA, n = 15; PSP, n = 24) formed the basis for a multicenter clinicopathological study. Clinical features at first and last clinical visit were abstracted from patient records on standardized forms following strict instructions. At the first visit (median 36 months after symptom onset), 24% of APD had FoG (CBD, 8%; DLB, 21%; PSP, 25%; MSA, 40%). Logistic regression analysis showed a significant association of FoG and urinary incontinence (P = 0.04) at first visit. At last visit, 47% of APD had FoG (CBD, 25%; PSP, 53%; DLB, 54%; MSA, 54%). Clinicopathological correlation based on routine postmortem examination failed to identify a consistent neuropathological substrate of FoG. This study demonstrates that (1) FoG is common in APD, and (2) urinary incontinence is significantly associated with FoG in these disorders. Whether FoG and urinary incontinence share similar neuropathological substrates remains to be determined by future studies.     

Prognostic implications of the motor symptoms of Parkinson's disease with respect to clinical,computertomographic and psychometric parameters

Summary Forty-four Parkinson patients (19 patients of the rigid-akinetic type, 13, of the rigid-akinetic-tremor type, and 12, of the tremor type) were included in a study in order to analyse correlations of the expression of the motor symptoms tremor, rigidity, akinesia, with other clinical parameters, computertomographic aspect of brain atrophy and psychometrically assessed cognitive parameters. Rigidity and akinesia are significantly positively correlated with the severity of motor dysability, stage of the disease, and brain atrophy, as is akinesia with a history of pharmacotoxic psychosis. Tremor is significantly negatively correlated with motor dysability, stage of the disease, and history of pharmacotoxic psychosis. Akinesia is correlated with visuomotor dysfunction (tested with Bender Gestalt Test) and rigidity with the depression score (Zung scale). The tremor type is favorable, the rigid-akinetic type unfavorable with respect to motor disability and psychosis.     

Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Process, format, and clinimetric testing plan.

This article presents the revision process, major innovations, and clinimetric testing program for the Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinson's Disease Rating Scale (UPDRS), known as the MDS-UPDRS. The UPDRS is the most widely used scale for the clinical study of Parkinson's disease (PD). The MDS previously organized a critique of the UPDRS, which cited many strengths, but recommended revision of the scale to accommodate new advances and to resolve problematic areas. An MDS-UPDRS committee prepared the revision using the recommendations of the published critique of the scale. Subcommittees developed new material that was reviewed by the entire committee. A 1-day face-to-face committee meeting was organized to resolve areas of debate and to arrive at a working draft ready for clinimetric testing. The MDS-UPDRS retains the UPDRS structure of four parts with a total summed score, but the parts have been modified to provide a section that integrates nonmotor elements of PD: I, Nonmotor Experiences of Daily Living; II, Motor Experiences of Daily Living; III, Motor Examination; and IV, Motor Complications. All items have five response options with uniform anchors of 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Several questions in Part I and all of Part II are written as a patient/caregiver questionnaire, so that the total rater time should remain approximately 30 minutes. Detailed instructions for testing and data acquisition accompany the MDS-UPDRS in order to increase uniform usage. Multiple language editions are planned. A three-part clinimetric program will provide testing of reliability, validity, and responsiveness to interventions. Although the MDS-UPDRS will not be published until it has successfully passed clinimetric testing, explanation of the process, key changes, and clinimetric programs allow clinicians and researchers to understand and participate in the revision process.     

Role of DAT‐SPECT in the diagnostic work up of Parkinsonism

The diagnosis of idiopathic Parkinson's disease (PD) can be achieved with high degrees of accuracy in cases with full expression of classical clinical features. However, diagnostic uncertainty remains in early disease with subtle or ambiguous signs. Functional imaging has been suggested to increase the diagnostic yield in parkinsonian syndromes with uncertain clinical classification. Loss of striatal dopamine nerve terminal function, a hallmark of neurodegenerative Parkinsonism, is strongly related to decreases of dopamine transporter (DAT) density, which can be measured by single photon emission computed tomography (SPECT). The use of DAT‐SPECT facilitates the differential diagnosis in patients with isolated tremor symptoms not fulfilling PD or essential tremor criteria, drug‐induced, psychogenic and vascular Parkinsonism as well as dementia when associated with Parkinsonism. This review addresses the value of DAT‐SPECT in early differential diagnosis, and its potential as a screening tool for subjects at risk of developing PD as well as issues around the assessment of disease progression. © 2007 Movement Disorder Society     

Dopamine D4 receptor polymorphism and idiopathic Parkinson's disease

Patients with idiopathic Parkinson's disease (IPD) are described as having markedly decreased novelty seeking characteristics. Since recent publications suggest an association between the dopamine D4 receptor polymorphism and novelty seeking, we investigated this polymorphism in a group of 122 patients with IPD and 127 healthy control subjects. We found similar allele and genotype frequencies in both groups and no association with the age of onset of symptoms. Therefore, the dopamine D4 receptor polymorphism does not confer genetic susceptibility to IPD and cannot explain the decreased novelty seeking in IPD patients.     

Ischemic stress induces deposition of amyloid β immunoreactivity in human brain

The histoblot immunostaining technique for locating and characterizing amyloidogenic proteins was used to obtain information about the relationship of cerebral ischemia/hypoxia to the accumulation of amyloid protein (Aß). We investigated brains of 131 subjects (ages 25–94 years, mean 72 years). Three distribution patterns of A immunoreactivity were identified: (1) colocalization with diffuse and neuritic plaques of Alzheimer's disease (AD) and aging; (2) diffuse punctate deposits in the cerebral cortex in association with small vessel cerebral vascular disease; and (3) cerebral cortical accumulation localized to arterial boundary zones and other regions susceptible to ischemic/hypoxic injury designated stress-induced deposits (SID). SID were not identified in tissue sections by immunohistochemical, Congo red or Bielschowsky silver techniques; no histological abnormalities were present in adjacent formalin-fixed tissue sections. SID occurred in subjects with histories of cerebral ischemia, and severe orthostatic hypotension. There was also an association with aging in general and with the incidence of neuritic plaques specifically. These latter findings are consistent with the hypothesis that brain ischemia/hypoxia plays a role in the pathogenesis of AD.     

Repetitive speech phenomena in Parkinson's disease

OBJECTIVES: Repetitive speech phenomena are morphologically heterogeneous iterations of speech which have been described in several neurological disorders such as vascular dementia, progressive supranuclear palsy, Wilson's disease, and Parkinson's disease, and which are presently only poorly understood. The present, prospective study investigated repetitive speech phenomena in Parkinson's disease to describe their morphology, assess their prevalence, and to establish their relation with neuropsychological and clinical background data. METHODS: Twenty four patients with advanced Parkinson's disease and 29 subjects with mid-stage, stable idiopathic disease were screened for appearance, forms, and frequency of repetitive speech phenomena, and underwent a neuropsychological screening procedure comprising tests of general mental functioning, divergent thinking and memory. Patients with advanced Parkinson's disease had a significantly higher disease impairment, longer disease duration, and an unstable motor response to levodopa with frequent on-off fluctuations. Both groups were well matched as to their demographical, clinical, and cognitive background. Perceptual speech evaluation was used to count and differentiate forms of repetitive speech phenomena in different speech tasks. To compare the effect of the motor state, the appearance of repetitive speech phenomena was also assessed in a subgroup of patients with advanced Parkinson's disease during the on versus the off state. RESULTS: Speech repetitions emerged mainly in two variants, one hyperfluent, formally resembling palilalia, and one dysfluent, stuttering-like. Both forms were present in each patient producing repetitive speech phenomena. The repetitive speech phenomena appeared in 15 patients (28.3 %), 13 of whom belonged to the advanced disease group, indicating a significant preponderance of repetitive speech phenomena in patients with a long term, fluctuating disease course. Repetitive speech phenomena appeared with almost equal frequency during the on and the off state of patients with advanced Parkinson's disease. Their distribution among different variants of speech was disproportional, with effort demanding speech tasks producing a significantly higher number of repetitive speech phenomena over semiautomatic forms of speech. CONCLUSIONS: In idiopathic Parkinson's disease repetitive speech phenomena seem to emerge predominantly in a subgroup of patients with advanced disease impairment; manifest dementia is not a necessary prerequisite. They seem to represent a deficit of motor speech control; however, linguistic factors may also contribute to their generation. It is suggested that repetitions of speech in Parkinson's disease represent a distinctive speech disorder, which is caused by changes related to the progression of Parkinson's disease.