Eugene Lai

Accuracy of clinical criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome)

We assessed the validity and interrater reliability of neurologists who, using four different sets of previously published criteria for the clinical diagnosis of progressive supranuclear palsy (PSP), also called Steele-Richardson-Olszewski syndrome, rated 105 autopsy-proven cases of PSP (n equals 24), Lewy body disease (n equals 29), corticobasal ganglionic degeneration (n equals 10), postencephalitic parkinsonism (n equals 7), multiple system atrophy (n equals 16), Picks disease (n equals 7), and other parkinsonian or dementia disorders (n equals 12). Cases were presented in random order to six neurologists. Information from each patients first and last visits to the medical center supplying the case was presented sequentially to the rater, and the raters diagnosis was compared with the neuropathologic diagnosis of each case. Interrater agreement for the diagnosis of PSP varied from substantial to near perfect, but none of the criteria had both high sensitivity and high predictive value. Because of these limitations, we used a logistic regression analysis to identify the variables from the data set that would best predict the diagnosis. This analysis identified vertical supranuclear palsy with downward gaze abnormalities and postural instability with unexplained falls as the best features for predicting the diagnosis. From the results of the regression analysis and the addition of exclusionary features, we propose optimal criteria for the clinical diagnosis of PSP. NEUROLOGY 1996;46: 922-930. TX.- In 1964, Steele, Richardson, and Olszewski described progressive supranuclear palsy (PSP), a brain neuro-degenerative disorder characterized by postural instability, parkinsonism, vertical supranuclear palsy, pseudobulbar palsy, and mild dementia. [1,2] However, the first clinical report on PSP [3,4] (also called Steele-Richardson-Olszewski syndrome) was published in 1904 and was soon followed by others. [5-7] When fully expressed, the clinical signs and symptoms of PSP are usually reliable for making the correct diagnosis, but cardinal signs, such as ophthalmoplegia, may be absent, or the only symptoms may be dementia or akinesia. [7-13] Neuropathologic examination remains the ``gold standard for the diagnosis of PSP. A clinical diagnosis can be mistakenly applied to pathologically determined diffuse Lewy body disease, corticobasal ganglionic degeneration (CBGD), cerebrovascular disease, Picks disease, or subcortical gliosis. [14-20] Conversely, neuropathologically confirmed PSP may be clinically mistaken for idiopathic Parkinsons disease (PD), pallidonigroluysial atrophy, cerebrovascular disease, Alzheimers disease (AD), or CBGD. [20-26]

Assessment of motor function after stereotactic pallidotomy

Despite a paucity of controlled data, stereotactic pallidotomy is increasingly used for the treatment of advanced Parkinsons disease (PD). To study the efficacy of the procedure on the cardinal PD features of rigidity, tremor, bradykinesia, and postural instability, we blindly rated randomized videos of 34 patients recorded in the off state immediately before and 3 months after unilateral stereotactic lesioning of the globus pallidus internus. Total off time Unified Parkinsons Disease Rating Scale motor scores improved 13.6% from 28.9 ± 7.5 to 25.0 ± 7.0(p < 0.001). Particularly robust improvement was seen in contralateral tremor, gait, and arising from a chair (p < 0.001). Significant improvement was also seen in ipsilateral tremor, contralateral and some ipsilateral dexterity measures, and body bradykinesia. Most other features tended toward improvement but did not reach statistical significance. We conclude that pallidotomy is a safe and effective treatment of parkinsonian symptoms, many of which improve bilaterally.

What are the obstacles for an accurate clinical diagnosis of Pick's disease? A clinicopathologic study

Several studies have evaluated the reliability and validity of the clinical diagnosis of Alzheimers disease (AD) using well-defined neuropathologic criteria, but none has attempted to evaluate the diagnostic accuracy of Picks disease. We determined the accuracy of the clinical diagnosis of Picks by presenting 105 autopsy-confirmed cases of Picks (n = 7) and related disorders (non-Picks, n = 98) as clinical vignettes in randomized order to six neurologists who were unaware of the autopsy findings. The group of raters had moderate to fair agreement for the diagnosis of Picks as measured by the κ statistics. The sensitivity for the diagnosis of Picks for the first visit (mean, 53 months after onset) and last visit (mean, 78 months after onset) was low (range, 0 to 71%), but specificity was near-perfect. Median positive predictive values at both visits were 83 to 85%. False-negative misdiagnoses mainly involved AD. False-positive diagnoses were rare and occurred with corticobasal degeneration (first visit) and with dementia with Lewy bodies (last visit). Picks was also misdiagnosed by primary neurologists. The best clinical predictors for the early diagnosis of Picks included frontal dementia, early cortical dementia with severe frontal lobe disturbances, absence of apraxia, and absence of gait disturbance at onset. However, the first neurologic evaluation in some of the Picks cases took place in advanced stages of the disease. Our findings suggest that this disorder is underdiagnosed in clinical practice. Although the low sensitivity for the clinical diagnosis of Picks is disappointing, our data suggest that when clinicians suspect Picks, their diagnosis is almost always correct. Absence of awareness of the main features of this disorder and of specificity of the frontal lobe syndrome may partially explain the low detection of Picks disease.

Weight gain following unilateral pallidotomy in Parkinson's disease

Objective: To determine the clinical correlates and infer pathogenesis of weight gain following pallidotomy in patients with Parkinsons disease (PD). Background: Surgical ablation of the globus pallidus internus (GPi) improves levodopa induced dyskinesias, moderately improves most other “cardinal” manifestations of PD, and has been noted to result in increased weight. Methods: We incorporated Unified Parkinsons Disease Rating Scales (UPDRS) subscales, the Beck depression inventory and feeding questionnaire data into a linear regression model in order to determine which post‐surgical change(s) may lead to weight gain over the first year following pallidotomy, n=60. Results: The mean weight gain 1 year after pallidotomy was 4.0±4.1 kg. Improvement in ‘off’ motor scores (P<0.005), especially gait subscores (P<0.0001), and to a lesser extent improvement in ‘on’ motor scores (P<0.05) predicted weight gain. Changes in dyskinesia ratings, mood, food intake, dysphagia, levodopa dose, weight loss in the year prior to pallidotomy, age, and duration of PD did not correlate with subsequent weight gain. Conclusion: The high correlation between post‐pallidotomy weight gain and ‘off’ motor scores, suggests that this phenomenon is related to some change in underlying homeostasis associated with changes in the cardinal manifestations of PD itself, rather than secondary changes resultant from the surgery.

Cognitive rehabilitation for executive dysfunction in Parkinson's disease: application and current directions.

Cognitive dysfunction in Parkinsons disease contributes to disability, caregiver strain, and diminished quality of life. Cognitive rehabilitation, a behavioral approach to improve cognitive skills, has potential as a treatment option to improve and maintain cognitive skills and increase quality of life for those with Parkinsons disease-related cognitive dysfunction. Four cognitive rehabilitation programs in individuals with PD are identified from the literature. Characteristics of the programs and outcomes are reviewed and critiqued. Current studies on cognitive rehabilitation in PD demonstrate feasibility and acceptability of a cognitive rehabilitation program for patients with PD, but are limited by their small sample size and data regarding generalization of effects over the long term. Because PD involves progressive heterogeneous physical, neurological, and affective difficulties, future cognitive rehabilitation programs should aim for flexibility and individualization, according to each patients strengths and deficits.

Retrospective application of a set of clinical diagnostic criteria for the diagnosis of multiple system atrophy

Summary. We estimated the accuracy of a modified commonly used set of clinical diagnostic criteria for the diagnosis of multiple system atrophy (MSA) by retrospectively applying the criteria to the features recorded by six neurologists who had evaluated 105 autopsy-confirmed cases (16 MSA and 89 non-MSA disorders). Cases were abstracted from the records of the patients first visit to an academic center, and were presented as clinical vignettes to six neurologists, each of whom recorded the main clinical features of the presented clinical vignette on a standardized form. Sensitivity and positive predictive values were chosen as validity outcome measures and were calculated by comparing the applied diagnostic criteria to the neuropathologic information. Of note, most MSA patients in this study (mainly those with Shy-Drager type) had not received levodopa therapy since the primary neurologists often had not perceived a need to administer this treatment. The validity of the retrospectively applied criteria for the diagnosis of possible MSA (sensitivity: median, 53%, range, 50–69%; positive predictive value: 30%, 28–39%) and probable MSA (sensitivity: 44%, 31–60%; positive predictive value: 68%, 54–80%) at the first visit was suboptimal. The best, still not perfect, accuracy for this set of diagnostic criteria was obtained when six out of eight features (sporadic adult onset, dysautonomia, parkinsonism, pyramidal signs, cerebellar signs, no levodopa response, no cognitive dysfunction, or no downward gaze supranuclear palsy) were present (median sensitivity, 59%; range, 50–75%; positive predictive value: 67%, 53–83%). This is the first study to validate criteria for the clinical diagnosis of MSA. Our data suggest that it is difficult to achieve an early and accurate clinical diagnosis of this disorder. The probability of correctly diagnosing MSA increases when at least six features of this modified set of criteria are present or when requiring the set for probable MSA.

Levodopa-induced dyskinesias treated by pallidotomy

Pallidotomy has been reported to improve parkinsonian symptoms, but its effects on levodopa-induced dyskinesia (LID) have not been thoroughly examined. We describe here the results of stereotactic, unilateral, posteroventral pallidotomy on LID in 42 patients (22 women), who were followed for up to 9 months. Their mean age was 60. 6+/-9.3 (range: 40-74), age at onset was 46.1+/-9.1 (range: 24-46), and duration of symptoms was 14.5+/-5.3 (range: 4-25) years. Three months following pallidotomy, the percent time with dyskinesia decreased from 37.0 to 17.3 (P<0.0001) and the percent time the patients were on with dyskinesias decreased even more, from 71.0 to 22.9 (P<0.0001). Furthermore, the number of patients with troublesome (moderate to violent) dyskinesia had decreased from 36 (86%) prior to surgery to only 5 (12%) after surgery. The mean unified Parkinson disease rating scale (UPDRS) scores for LID-related disability and pain decreased from 1.95 to 0.74 (P<0. 0001) and from 1.02 to 0.17 (P<0.0001), respectively. Since the pre- and post-pallidotomy daily levodopa dosage remained essentially the same, the improvement in LID could not be attributed to a reduction in levodopa. Surgery-related complications occurred in eight (19%) patients, but none of them had persistent disability as a result of these complications. We conclude that pallidotomy is an effective and safe procedure in the treatment of medically intractable LID.

Short and long-term motor and cognitive outcome of staged bilateral pallidotomy: a retrospective analysis.

SummaryBackground. We investigated retrospectively the short and long-term motor and cognitive functioning of staged bilateral pallidotomy using motor testing and a comprehensive neuropsychological battery before and after each procedure.n Methods. Fifteen patients with idiopathic Parkinson’s disease were assessed at baseline and at least 3 months after each of their two staged surgeries. Motor and neuropsychological results were compared to 15 non-surgical Parkinson’s disease patients matched for disease stage and mental status. In addition, nine bilateral pallidotomy patients were evaluated for long-term cognitive changes (>2 years).n Findings. Bilateral pallidotomy patients demonstrated significant improvements in motor functioning in the “on” and “off” states and with dyskinesias after the first surgery, with an additional improvement reported for dyskinesias after the second procedure. On long-term follow-up, dyskinesia improvements were maintained. Bilateral pallidotomy patients did not show significant cognitive declines following both procedures on the short-term follow-up and when compared to the Parkinson’s disease group. However, significant cognitive declines were found on the long-term follow-up evaluation.n Conclusions. Parkinson’s disease patients received significant short- and long-term motor benefits, particularly reduced dyskinesias, following staged bilateral pallidotomy without significant short-term cognitive consequences. Two years following the second procedure, bilateral pallidotomy patients tended to show an increase in both motor and non-motor symptoms of Parkinson’s disease, particularly cognitive decline.

Alleviation of drenching sweats following subthalamic deep brain stimulation in a patient with Parkinson's disease — A case report

We report a patient with Parkinsons disease whose whole body drenching sweats were completely alleviated by stimulation of the subthalamic nucleus and/or adjacent structures. Sweating reappeared 4h after the pulse generator (stimulation) was turned off and ceased when stimulation was resumed. Imaging studies with reconstruction indicated that stimulation of, or spread of stimulation from, the caudal medial aspect of the right subthalamic nucleus and/or the caudal aspect of the ventral thalamus/zona incerta may be responsible for alleviating the drenching sweats.

Effect of Subthalamic Nucleus or Globus Pallidus Interna Stimulation on Oculomotor Function in Patients with Parkinson’s Disease

Background: Deep brain stimulation (DBS) of either the globus pallidus interna (GPi) or subthalamic nucleus (STN) is similarly effective for treating somatomotor manifestations of Parkinson’s disease (PD), but differences in how stimulation of each target affects oculomotor function are poorly understood. Objective: We sought to determine if stimulation of the STN, but not the GPi, affects oculomotor function in PD patients. Methods: Nineteen PD patients with DBS implants (8 bilateral GPi, 9 bilateral STN and 2 unilateral STN) were studied. Testing was performed with stimulation on, then off. Somatomotor function was tested using the Unified Parkinson’s Disease Rating Scale (UPDRS) motor exam. For oculomotor testing, patients performed pro- and antisaccade tasks while monitored with an infrared eye tracker. Saccadic latency, saccadic intrusions, and square-wave jerks (SWJs) were measured for each trial. Results: As expected, UPDRS motor scores improved with both GPi and STN stimulation. With GPi stimulation, there was no significant difference in oculomotor function with stimulation on or off. However, with STN stimulation on, there was a significant increase in the mean number of SWJs/s, as well as a significant decrease in latency for both pro- and antisaccade tasks. Conclusion: Stimulation of either GPi or STN had similar effects on somatomotor function, but only STN stimulation significantly altered oculomotor function.