Showing papers by "William G. Ondo published in 2000"
TL;DR: These behaviors are consistent, although not specific, with what would be expected in an animal model of RLS, and despite a large number of observations, the small number of lesioned animals precluded formal statistical analysis.
Abstract: Pursuant to the clinical suspicion that restless legs syndrome (RLS) may involve dopaminergic diencephalic spinal neurons (A11), we performed stereotaxic bilateral 6-hydroxydopamine (6-OHDA) lesions into the A11 nucleus to observe for any behavioral correlates similar to this clinical condition. Pathologic examination demonstrated a 54% reduction in A11 tyrosine hydroxylase staining cells in rats injected with 6-OHDA versus sham treatment. Multiple blindly rated 90-120-minute video epochs demonstrated an increased average number of standing episodes (14.4+/-11.7 versus 7.3+/-5.5 episodes/epoch) and increased total standing time (38.9+/-20.5 versus 25.3+/-12.2 minutes/epoch) but similar total sleep time in four lesioned rats when compared with two sham rats. Treatment of the lesioned rats with intramuscular pramipexole subsequently resulted in fewer standing episodes (4.4+/-3.3 versus 14.4+/-11.7 episodes/epoch) and less total standing time (20.9+/-12.3 versus 38.9+/-20.5 minutes/epoch) when compared with untreated lesioned rats. Despite a large number of observations, the small number of lesioned animals precluded formal statistical analysis. These behaviors are consistent, although not specific, with what would be expected in an animal model of RLS.
272 citations
TL;DR: To better understand genetic characteristics of restless legs syndrome (RLS) and identify nongenetic factors that may influence phenotype, the authors studied 12 identical twins in which at least one member expressed RLS.
Abstract: To better understand genetic characteristics of restless legs syndrome (RLS) and identify nongenetic factors that may influence phenotype, the authors studied 12 identical twins in which at least one member expressed RLS. Ten of the 12 twin pairs were concordant for RLS symptoms. Despite the high concordance rate, the disease severity, age at onset, and symptom descriptions often varied between twins. Birth order, birth weight, and serum ferritin levels did not predict RLS severity or age at onset.
197 citations
TL;DR: Gabapentin may be effective in some cases of ET and statistical regression models did not demonstrate any significant predictors for response, but the results were similar for high and low doses.
Abstract: Essential tremor (ET) is a common movement disorder that often becomes refractory to conventional pharmacologic management. Open-label studies suggest that gabapentin is efficacious for ET, but the results of controlled trials have been mixed. To determine the efficacy and tolerability of gabapentin in ET, we conducted a double-blind, placebo-controlled, cross-over trial evaluating two doses (1800 mg per day and 3600 mg per day; N = 25). Patients on other ET medications were maintained on their concurrent medications for 3 months prior to study initiation and throughout the study. Twenty patients (mean age, 69.9 +/- 6.1 yrs) completed the study. Overall, patient global assessments (p <0.05), observed tremor scores (p <0.005), water pouring scores (p <0.05), and activities of daily living scores (p <0.005) significantly improved. Accelerometry scores, spirographs, and investigator global impression scores did not improve. The results were similar for high and low doses. Statistical regression models did not demonstrate any significant predictors for response. Gabapentin may be effective in some cases of ET.
123 citations
TL;DR: Computerized posturography testing reliably differentiated early PSP from early PD and age-matched controls, and suggested a vestibular pattern and overreliance on visual cues, even when incorrect.
Abstract: Background Progressive supranuclear palsy (PSP) is a neurodegenerative disorder that is frequently mistaken for Parkinson's disease (PD) in its early stages. Objective To compare balance measures using computerized posturography in patients with early PSP and early PD. Methods We performed computerized posturography (SMART Balance Master; NeuroCom International, Inc, Clackamas, Ore) in 20 patients with clinically diagnosed mild to moderate PSP (ambulatory) and compared results with those from 20 patients with PD of similar age and disease duration who were not receiving medications, and from 20 healthy age- and sex-matched controls. Sensory organization testing (SOT), limits of stability (LOS), and toes-up perturbations (4° at 50° per second) were tested while receiving and not receiving a combination of oral carbidopa (25 mg) and levodopa (250 mg) in the PSP group. Clinical assessment included Unified Parkinson's Disease Rating Scale, Performance-oriented assessments, and functional reach. Results When compared with the PD and control groups, total LOS time ( P P 2,57 = 29.6; P P = .003), eyes open and platform sway ( P = .003), eyes closed and platform sway ( P P 2 = 11.3; P = .002). Levodopa administration did not significantly improve any aspect of posturography testing in PSP. In differentiating PSP from PD, LOS time and SOT condition of eyes open and platform and visual sway were nearly 100% sensitive and 100% specific (canonical correlation, 0.91). Conclusions Computerized posturography testing reliably differentiated early PSP from early PD and age-matched controls. The PSP group demonstrated severely contracted limits of stability with probable deficits in motor programming. Results of SOT in PSP suggested a vestibular pattern and overreliance on visual cues, even when incorrect. The absence of short-latency responses (monosynaptic reflex arch) suggests an additional disturbance in the spinal cord or peripheral nervous system.
63 citations
TL;DR: The condition seemed to be dose dependent but also idiosyncratic, as it resulted in extensive medical evaluation in some patients and was only minimally responsive to diuretic therapy.
Abstract: Background Pramipexole, a new dopamine agonist, effectively treats early and advanced Parkinson disease and restless legs syndrome. Objectives To report the clinical features of and to investigate the predisposing factors and eventual outcomes in patients who developed peripheral edema (PE) following treatment with pramipexole. Design Retrospective case series in a tertiary referral center. Results Of the 300 patients who were receiving pramipexole therapy, 17 patients had mild to severe PE, which was attributable to the medication. Fifteen patients had Parkinson disease and 2 patients had restless legs syndrome. The mean (±SD) time of onset of PE after pramipexole therapy was started was 2.6 ± 3.6 months (range, 0.25-11 months). The mean (±SD) dose at onset of PE was 1.7 ± 1.0 mg/d (dose range, 0.75-3 mg/d) and the mean (±SD) dose when PE was at its maximum was 2.6 ± 0.7 mg/d (dose range, 1.5-3 mg/d). In all cases, the PE rapidly abated with discontinuation of therapy, and in all cases that we rechallenged, it rapidly returned. The condition seemed to be dose dependent but also idiosyncratic, as we could not identify any predisposing features. It resulted in extensive medical evaluation in some patients and was only minimally responsive to diuretic therapy. Conclusion Peripheral edema should be included among the potential adverse events associated with pramipexole therapy.
55 citations
TL;DR: 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.
Abstract: Objective - To determine the clinical correlates and infer pathogenesis of weight gain following pallidotomy in patients with Parkinson's 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 Parkinson's 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.
54 citations
TL;DR: Improvements in parkinsonian symptoms were maintained in both “off” and “on” states in 62 patients at 12 months after PVP and in 41 patients who were followed for 18 months or longer.
Abstract: The authors describe results of unilateral posteroventral pallidotomy (PVP) in 89 patients with PD. At 3 months after surgery, 81.9% of the patients reported marked or moderate improvement in their parkinsonian symptoms. Postoperative Unified PD Rating Scale "off" state mean total motor score improved by 35.5% and the mean activities of daily living score by 33.7% (p <0.001). Improvements in parkinsonian symptoms were maintained in both"off" and "on" states in 62 patients at 12 months after PVP and in 41 patients who were followed for 18 months or longer (mean 26.6 months).
52 citations
50 citations
TL;DR: It is suggested that neuropathy and serum iron deficiency do represent secondary forms of RLS, and serologic investigation unless there are overt clinical signs is not recommended.
Abstract: Diagnostic criteria for restless legs syndrome (RLS) have been established; however, the pathophysiology of this common condition remains elusive. Several secondary forms of RLS potentially include renal failure, iron deficiency, pregnancy, and neuropathy. RLS has also been reported in approximately 25% of patients diagnosed with rheumatoid arthritis and Sjogren's syndrome. We performed clinical and serologic evaluations on 68 patients diagnosed with RLS to determine how many may have concurrent rheumatologic disease that could be causing their RLS symptoms. We compared these with other postulated secondary causes of RLS. No patient had clinical evidence of rheumatologic disease, and only four had any positive serologic evaluations (two positive SSA/SSB and two mildly elevated RF titers). Three of these had a positive family history for RLS. Patients without a family history of RLS did have lower ferritin levels, more cases of neuropathy, and an older age at symptom onset. We do not think rheumatologic disease represents a significant secondary cause of RLS and do not recommend serologic investigation unless there are overt clinical signs. In contrast, our study suggests that neuropathy and serum iron deficiency do represent secondary forms of RLS.
49 citations
TL;DR: Additional research is needed to further elucidate the pathophysiology of RLS, through obtaining post-mortem specimens and refinement of neuroimaging and neurophysiologic techniques, to result in better understanding of this disease at the molecular level.
46 citations
TL;DR: Clinical measures suggested improvement during the APO "on" period after the addition of tolcapone, but neither reached statistical significance, and further trials, involving larger samples are needed to clearly establish the pharmacokinetic and clinical effect of to lcapone in PD patients taking APO.