Subject-investigator reproducibility of the Unified Parkinson's Disease Rating Scale

ObjectiveTo evaluate the subject-investigator agreement on the Unified Parkinson’s Disease Rating Scale (UPDRS) subsections I and II.MethodsSubject-investigator agreement was estimated at baseline and endpoint by Kappa statistics for individual items and concordance correlations for subscale totals using data from two NIH Exploratory Trials in Parkinson’s Disease studies.ResultsAll but two questions had moderate subject-investigator agreement at baseline and endpoint. Participants consistently rated their disease activity worse that investigators.ConclusionUPDRS self-administration produces similar results to investigator-administration. Although slightly elevated, UPDRS self-administration can be accommodated in a clinical trial setting.     

Ocular motor abnormalities in progressive supranuclear palsy

Eleven patients, 7 males and 4 females, of progressive supranuclear palsy (PSP) were examined neuro-otologically for the purpose of elucidating the characteristics of ocular motor abnormalities. All cases were admitted to our hospital and age at onset was from 52 to 71 years old, duration of illness was 2 to 11 years. Range of voluntary eye movements and abnormal eye movements including nystagmus were examined on naked eyes and with electronystagmography (ENG). Smooth pursuit movements and saccadic eye movements were tested both horizontally and vertically by using visual tracking method with ENG recordings. Optokinetic nystagmus test and caloric test with visual suppression test were also performed. These neurotological examinations were made repetitively in 5 cases and their progressions were observed. Vertical gaze palsy and convergence palsy were observed in all cases as the initial symptom. In this study downward gaze was more severely disturbed than upward gaze. Using ENG, saccadic eye movements (saccades) were disturbed earlier than smooth pursuit movements. Hypometric saccades and decreased saccadic velocity were common abnormalities. In the later stage of the disease, horizontal eye movements were also disturbed. In four cases bilateral adduction palsy was added to vertical gaze paralysis so that the lesion of the MLF to oculomotor nucleus was suggested to exist. These voluntary eye movements were worsened gradually as the disease progressed. By using ENG we could find so called abnormal eye movements more frequently than the previous reports. Eight patients demonstrated horizontal gaze nystagmus, and rebound nystagmus were observed in four cases.(ABSTRACT TRUNCATED AT 250 WORDS)     

The Dementia Rating Scale in Alzheimer's disease,Huntington's disease and progressive supranuclear palsy

The Dementia Rating Scale (DRS) comprises a series of five subtests which assess attention, memory, initiation/perseveration, construction, and conceptualisation. It can be delivered in full in approximately 30 min, making it a useful test for the detection and estimation of the overall level of dementia. We analysed the pattern of subscale test scores in patients with cortical and subcortical dementias, who were matched for their overall level of dementia on this scale. Patients with dementia of Alzheimer's type were more impaired than patients with Huntington's disease (HD) and progressive supranuclear palsy (PSP) on the memory subtest, whereas patients with HD and PSP were more impaired on the initiation/perseveration subtest. This is evidence in favour of the concept of cortical and subcortical dementias as separate, although overlapping, entities. Qualitative differences in the pattern of cognitive impairment in these disorders can be detected with a brief cognitive status examination.     

Co-occurrence of Parkinson's disease with progressive supranuclear palsy

Parkinson's disease (PD) and progressive supranuclear palsy (PSP) are distinct neurodegenerative disorders. We describe an 81-year-old woman with 3 years of progressive gait unsteadiness, frequent falls, and mild cognitive dysfunction, all considered clinically to be an early fronto-temporal neurodegenerative disorder. She died of an acute myocardial infarction. Examination of her brain revealed alpha-synuclein- and tau-positive inclusions diagnostic of PD and PSP. Immunoelectron microscopy and Western blot analysis confirmed combined PD/PSP. This case provides strategies for the reliable molecular validation of concomitant PD and PSP, and demonstrates the utility of these techniques in patients with atypical clinical presentations.     

The ocular motor defects in progressive supranuclear palsy

The results of quantitative infrared horizontal eye movement recordings in 8 patients with progressive supranuclear palsy are presented. Some of the patients had total paralysis of vertical movements, but none had completely lost the ability to perform horizontal eye movements. All patients had a defect in ocular fixation previously undescribed in this condition: the universal presence of square-wave jerks. Analysis of refixation sacades demonstrated hypometria, slow velocity/amplitude relationships, and profound prolongation of duration. The pursuit abnormality, characterized clinically by “cogwheel” eye movements, represented the inability to match eye velocity to target velocity. The ratio of peak eye velocity to peak target velocity (pursuit gain) was 0.2 to 0.5. Defects in the vestibuloocular reflex included inability to increase the gain of the reflex (ratio of peak eye velocity to head velocity) during viewing of a visible, stationary target and failure to suppress the reflex when viewing a target rotating with the head.     

The Unified Parkinson's Disease Rating Scale (UPDRS): Status and recommendations

The Movement Disorder Society Task Force for Rating Scales for Parkinson's Disease prepared a critique of the Unified Parkinson's Disease Rating Scale (UPDRS). Strengths of the UPDRS include its wide utilization, its application across the clinical spectrum of PD, its nearly comprehensive coverage of motor symptoms, and its clinimetric properties, including reliability and validity. Weaknesses include several ambiguities in the written text, inadequate instructions for raters, some metric flaws, and the absence of screening questions on several important non‐motor aspects of PD. The Task Force recommends that the MDS sponsor the development of a new version of the UPDRS and encourage efforts to establish its clinimetric properties, especially addressing the need to define a Minimal Clinically Relevant Difference and a Minimal Clinically Relevant Incremental Difference, as well as testing its correlation with the current UPDRS. If developed, the new scale should be culturally unbiased and be tested in different racial, gender, and age‐groups. Future goals should include the definition of UPDRS scores with confidence intervals that correlate with clinically pertinent designations, “minimal,” “mild,” “moderate,” and “severe” PD. Whereas the presence of non‐motor components of PD can be identified with screening questions, a new version of the UPDRS should include an official appendix that includes other, more detailed, and optionally used scales to determine severity of these impairments. © 2003 Movement Disorder Society     

Comparison of motor, cognitive, and behavioral features in progressive supranuclear palsy and Parkinson's disease.

Major clinical features and global measures were systematically evaluated and compared in progressive supranuclear palsy (PSP) and Parkinson's disease (PD). In addition to gaze palsy and early postural instability in PSP, absence of levodopa-induced dyskinesia, frontalis muscle overactivity, primitive reflexes, visuospatial impairment, and substantial frontal behavioral disturbances differentiated almost all patients with this disorder from PD. For PSP, behavioral changes related to severity of general disability, thereby challenging previous models of relationships between behavior, motor, and cognitive disturbance for this disorder.     

Comparison of the Unified Parkinson's Disease Rating Scale and the Short Parkinson's Evaluation Scale in patients with Parkinson's disease after levodopa loading

The Short Parkinson's Evaluation Scale has been compiled and validated previously (Clinical Neuropharmacology, 1997). In the present study, we have assessed and compared the motor scoring of the Unified Parkinson's Disease Rating Scale and the Short Parkinson's Evaluation Scale in 23 patients (mean age, 61.8 years) with Parkinson's disease. Patients were 12 hours off medication at the beginning of the series. They were then given levodopa, 125 mg and 250 mg, on different days and were evaluated each 30 minutes for 2 hours. In addition, patients' motor skills (finger tapping and walking velocity) were measured at each time. Analysis of variance with repeated measures was applied. The results presented show that both scales have the same ability to measure levodopa-dose effect within time. In addition, Spearman's correlation coefficients showed a negative correlation between finger tapping and upper-limb impairment and a positive correlation between walking velocity and lower-limb impairment in both scales.In summary, the present results suggest that Short Parkinson's Evaluation Scale is a useful tool in assessing the effect of medication, having the advantage of being easier and quicker.     

Cerebellar rTMS for motor control in progressive supranuclear palsy

BackgroundStimulatory cerebellar TMS is a promising tool to improve motor control in neurodegenerative disorders.Objective/hypothesis: Our goal was to use 10Hz cerebellar rTMS to augment cerebellar-brain inhibition (CBI) for improved postural stability and speech in patients with progressive supranuclear palsy (PSP).MethodsWe performed CBI assessments with neuronavigation before and after high frequency cerebellar rTMS or sham TMS in two patients with PSP, using a double cone coil for the conditioning pulse and a figure-of-eight coil for the test pulse and treatments. We collected posturography data and speech samples before and after treatment.ResultsAfter treatment, CBI increased by 50% in subject 1 and by 32% in subject 2, and postural stability and speech improved. The protocol was well tolerated, but the sham was not consistently believable.ConclusionCerebellar rTMS may improve postural stability and speech in PSP, but cooled coils with vibrotactile sham capability are needed for larger future studies.     

Prediction of motor Unified Parkinson's Disease Rating Scale scores in patients with Parkinson’s disease using surface electromyography

ObjectiveParkinson's disease (PD) is a chronic neurodegenerative disorder with increasing prevalence in the elderly. Especially patients with advanced PD often require complex medication regimens due to fluctuations, that is abrupt transitions from ON to OFF or vice versa. Current gold standard to quantify PD-patients’ motor symptoms is the assessment of the Unified Parkinson's Disease Rating Scale (UPDRS), which, however, is cumbersome and may depend upon investigators. This work aimed at developing a mobile, objective and unobtrusive measurement of motor symptoms in PD.MethodsData from 45 PD-patients was recorded using surface electromyography (sEMG) electrodes attached to a wristband. The motor paradigm consisted of a tapping task performed with and without dopaminergic medication. Our aim was to predict UPDRS scores from the sEMG characteristics with distinct regression models and machine learning techniques.ResultsA random forest regression model outnumbered other regression models resulting in a correlation of 0.739 between true and predicted UPDRS values.ConclusionsPD-patients’ motor affection can be extrapolated from sEMG data during a simple tapping task. In the future, such records could help determine the need for medication changes in telemedicine applications.SignificanceOur findings support the utility of wearables to detect Parkinson's symptoms and could help in developing tailored therapies in the future.     

Dystonia in progressive supranuclear palsy.

OBJECTIVES: To document the nature, distribution, and frequency of dystonic symptoms in progressive supranuclear palsy (PSP). METHODS: Charts and videotapes of all clinically diagnosed patients with PSP seen between 1983 and 1993 were reviewed and the occurrence, nature, and distribution of all dystonic symptoms were recorded. RESULTS: Of 83 identified cases 38 had some dystonic features. Twenty (24%) had blepharospasm (one was induced by levodopa), 22 (27%) had limb dystonia (one was induced by electroconvulsive therapy and another by levodopa), 14 (17%) had axial dystonia in extension, one had oromandibular dystonia induced by levodopa, and two had other cranial dystonias. Six patients had limb dystonia as an early or presenting feature, sometimes leading to misdiagnosis of cortical-basal ganglionic degeneration. All three patients who had postmortem confirmation of the diagnosis had other concurrent disease. One patient with bilateral limb dystonia and blepharospasm had evidence of previous hydrocephalus and severe arteriosclerotic changes. One with arm dystonia also had cerebrovascular disease and one with hemidystonia also had rare swollen chromatolytic neurons in the frontotemporal cortex. CONCLUSIONS: Dystonia is a common manifestation of PSP. Limb dystonia is particularly common and may indicate the presence of concurrent disease. When dystonia occurs in PSP, dopaminergic medication should be cautiously reduced or discontinued to rule out the possibility of treatment induced symptoms.     

Elementary motor perseveration in early diagnosis of progressive supranuclear palsy

Three patients with progressive supranuclear palsy (PSP) with different symptoms at onset presented intense elementary motor perseveration before the appearance of the distinctive features of the illness. In elementary motor perseveration once an element of a movement has begun it is no longer inhibited at the right time and continues unchecked. Perseverations were observed in these patients during tests for dysdiadochokinesia, for reproduction of rhythmic structures and during the drawing of simple geometric shapes. Though this sign has not yet been described in PSP it is possible that an adequate search for its occurrence may show it to be an important sign for early diagnosis and an element for the clinical characterization of PSP.     

Mutational analysis of the tau gene in progressive supranuclear palsy.

OBJECTIVE: To identify genetic mutations in the coding regions and the splice-donor sites of the tau gene on chromosome 17q in individuals with progressive supranuclear palsy (PSP). BACKGROUND: Several studies provide evidence for linkage disequilibrium between a PSP disease gene and allelic variants of the tau gene. However, a causative mutation has not been identified. METHODS: We designed a study to search for genetic mutations in 15 coding regions of the tau gene including the splice-donor sites in 22 patients with PSP by comparing the mobility shifts on single-strand conformation analysis with those of age-matched controls. Fragments with altered migration were sequenced directly and compared for differences in nucleotide composition. Restriction enzyme digests were used to confirm single base-pair substitutions. RESULTS: Significant differences in mobility shifts were found in exons 1, 4A, and 8 between affected individuals and age-matched controls. All individuals with PSP had a common extended haplotype characterized by a homozygous polymorphism in the 5' splice site untranslated region of exon 1, two missense mutations in exon 4A (Asp285Asn, Ala289Val), and a nonsense mutation in the 5' splice site of exon 8. CONCLUSIONS: This study demonstrates that 22 unrelated progressive supranuclear palsy (PSP) patients have four identical sequence variants within the tau gene that are not present in 24 age-matched controls. Although the functional significance of these results on tau protein expression is unknown, the presence of this "susceptibility" haplotype in individuals may place them at risk for developing PSP.     

Brain iron deposition fingerprints in Parkinson's disease and progressive supranuclear palsy

It can be difficult to clinically distinguish between classical Parkinson's disease (PD) and progressive supranuclear palsy. Previously, there have been no biomarkers that reliably allow this distinction to be made. We report that an abnormal brain iron accumulation is a marker for ongoing neurodegeneration in both conditions, but the conditions differ with respect to the anatomical distribution of these accumulations. We analyzed quantitative T2' maps as markers of regional brain iron content from PD and progressive supranuclear palsy patients and compared them to age-matched control subjects. T2-weighted and T2*-weighted images were acquired in 30 PD patients, 12 progressive supranuclear palsy patients, and 24 control subjects at 1.5 Tesla. Mean T2' values were determined in regions-of-interest in the basal ganglia, thalamus, and white matter within each hemisphere. The main findings were shortened T2' values in the caudate nucleus, globus pallidus, and putamen in progressive supranuclear palsy compared to PD patients and controls. A stepwise linear discriminant analysis allowed progressive supranuclear palsy patients to be distinguished from PD patients and the healthy controls. All progressive supranuclear palsy patients were correctly classified. No progressive supranuclear palsy patient was classified as a healthy control, no healthy controls were incorrectly classified as having progressive supranuclear palsy, and only 6.7% of the PD patients were incorrectly classified as progressive supranuclear palsy. Regional decreases of T2' relaxation times in parts of the basal ganglia reflecting increased brain iron load in these areas are characteristic for progressive supranuclear palsy but not PD patients.     

The Unified Parkinson's Disease Rating Scale: validation study of the mentation, behavior, and mood section.

The objective of this study was to examine the validity of the mentation, behavior, and mood items included in Part I of the Unified Parkinson's Disease Rating Scale (UPDRS) and to assess its usefulness to screen for dementia, psychosis, depression, and apathy. A consecutive series of 168 patients with PD were assessed by neurologists with the UPDRS, and by psychiatrists using a comprehensive neuropsychiatric evaluation blind to each other's ratings. ROC analysis demonstrated that a score of 2 or greater on the intellectual impairment item of the UPDRS had 60% sensitivity and 92% specificity to detect dementia, as diagnosed with DSM-IV criteria. When a score of 23 or lower on the MMSE was included as an additional classification variable, the sensitivity increased to 85%. A score of 2 or greater on the thought disorder item had 43% sensitivity and 92% specificity to detect psychotic symptoms (delusions or hallucinations). A score of 2 or greater on the depression item had 77% sensitivity and 82% specificity to detect major depression as diagnosed with DSM-IV criteria. Finally, a score of 2 or greater on the motivation/initiative item had 73% sensitivity and 65% specificity to detect apathy, as diagnosed with a standardized criteria. When the sample was divided into mild (i.e. Hohen-Yahr stages I and II) versus moderate-severe PD (i.e. Hohen-Yahr stages III-V), findings remained unchanged, except that the UPDRS show unacceptably low accuracy to detect psychosis in mild PD. The mentation, behavior, and mood section of the UPDRS is an adequate screen for depression and apathy, and has adequate sensitivity to detect dementia when combined with the Mini-Mental State Exam, but has low sensitivity to detect psychosis.