Showing papers in "Movement Disorders in 1999"

Core assessment program for surgical interventional therapies in Parkinson's disease (CAPSIT-PD).

Abstract: In 1992 the Core Assessment Program for Intracerebral Transplantations (CAPIT) was published providing the minimal requirements for a common patient evaluation protocol. Despite the intent, the program was thought to be too laborious to carry out in large scale trials, and it also lacked evaluations of cognitive functions and quality of life. Moreover, the CAPIT was designed for neural transplantation only and has not been revised since. Since then, pallidotomy and deep brain stimulation have emerged as additional treatment modalities but there exists no common tool for evaluation of, and between, the techniques. In 1996, within the framework of NECTAR (Network for European CNS Transplantation and Restoration), a dedicated program entitled "Neurosurgical Interventions in Parkinson's Disease" (NIPD) was funded by the European Union Biomed 2 program to develop a new Core Assessment Program for Surgical Interventional Therapies in PD (CAPSIT-PD) and to establish an European registry for patients with PD subjected to functional neurosurgery. This article presents the recommendations of this new program.

Fatigue in patients with Parkinson's disease

Abstract: OBJECTIVE To compare the prevalence of fatigue in patients with Parkinson's disease (PD) with that in healthy elderly people and to explore the suggestion that fatigue is an independent symptom of PD. DESIGN Questionnaire survey. SETTING Community-based population. PATIENTS AND CONTROL SUBJECTS 233 patients derived from a prevalence study in the county of Rogaland, Norway and 100 healthy elderly people with the same age and sex distribution as the patients with PD. MAIN OUTCOME MEASURE A score for fatigue was obtained by combining the results from the rating scale for low energy in the Nottingham Health Profile (NHP) with the results obtained from a 7-point scale devised to evaluate fatigue. RESULTS 44.2% of the patients with PD and 18% of the healthy elderly control subjects reported fatigue. Fatigue was associated with depression, dementia, disease severity, disease duration, levodopa dose, and the use of sleeping pills. In a multivariate analysis, only depressive symptoms reached statistical significance. The prevalence of fatigue in patients with PD who were not depressed, demented, or had a sleeping disturbance was similar to that found in the total PD population. CONCLUSION Fatigue is a common symptom in PD. Although fatigue correlated with depressive symptoms, patients with PD who did not have depression, dementia, or sleep disturbances also reported a high prevalence of this symptom. This supports the hypothesis that fatigue is an independent symptom of PD overlapping with, but not causally related to, the concurrence of depressive symptoms.

Further studies on periodic limb movement disorder and restless legs syndrome in children with attention-deficit hyperactivity disorder.

Abstract: Fourteen consecutive children who were newly diagnosed with attention-deficit hyperactivity disorder (ADHD) and who had never been exposed to stimulants and 10 control children without ADHD underwent polysomnographic studies to quantify Periodic Limb Movements in Sleep (PLMS) and arousals. Parents commonly gave both false-negative and false-positive reports of PLMS in their children, and a sleep study was necessary to confirm their presence or absence. The prevalence of PLMS on polysomnography was higher in the children with ADHD than in the control subjects. Nine of 14 (64%) children with ADHD had PLMS at a rate of >5 per hour of sleep compared with none of the control children (p 20 per hour of sleep. Many of the PLMS in the children with ADHD were associated with arousals. Historical sleep times were less for children with ADHD. The children with ADHD who had PLMS chronically got 43 minutes less sleep at home than the control subjects (p = 0.0091). All nine children with ADHD who had a PLMS index of >5 per hour of sleep had a long-standing clinical history of sleep onset problems (>30 minutes) and/or maintenance problems (more than two full awakenings nightly) thus meeting the criteria for Periodic Limb Movement Disorder (PLMD). None of the control children had a clinical history of sleep onset or maintenance problems. The parents of the children with ADHD were more likely to have restless legs syndrome (RLS) than the parents of the control children. Twenty-five of 28 biologic parents of the children with ADHD and all of the biologic parents of the control children were reached for interview. Eight of twenty-five parents of the children with ADHD (32%) had symptoms of RLS as opposed to none of the control parents (p = 0.011). PLMS may directly lead to symptoms of ADHD through the mechanism of sleep disruption. Alternative explanations for the association between ADHD and RLS/PLMS are that they are genetically linked, they share a common dopaminergic deficit, or both.

Excessive daytime sleepiness and sleep benefit in Parkinson's disease: a community-based study.

Abstract: The objective of this study was to investigate the frequency of excessive daytime sleepiness (EDS) and the beneficial effect of sleep on motor performance in an unselected community-based sample of patients with Parkinson's disease (PD). Furthermore, we wanted to identify possible risk factors to these phenomena. Detailed information on somnolence and sleep during daytime, as well as sleep benefit (SB) on awakening, was collected through a questionnaire among 245 patients with PD. Daytime somnolence was graded in groups of no somnolence, mild daytime sleepiness, and EDS. In addition, the occurrence of somnolence in the patients with PD was compared with the occurrence among control groups of patients with diabetes mellitus and of healthy elderly subjects. The correlations between EDS and SB and various motor- and non-motor symptoms of PD were evaluated. Among the patients with PD, 15.5% experienced EDS, significantly more than in the patients with diabetes mellitus (4%) and the healthy control subjects (1%). The frequency of mild daytime sleepiness was similar (10%) in patients with PD and control subjects. The patients with EDS had significantly higher staging of PD, were more disabled, and showed a higher frequency of cognitive decline compared with the patients without somnolence. They also had been using levodopa for a longer time and had more hallucinations. The occurrence of nocturnal sleeping problems and the use of sleeping pills was similar in the two groups, as was the mean age at examination, duration of PD, and presence of fluctuations and dyskinesias. SB was found in 42.2% of the patients with PD. These patients had been using levodopa for significantly longer and had significantly more fluctuations and dyskinesias compared with the patients without SB. Our results suggest that mild daytime sleepiness may be a result of normal aging, whereas more severe EDS can be explained by the neuropathologic changes of PD. The data from this community-based study confirms the previously reported high frequencies of SB.

Nutritional and occupational factors influencing the risk of Parkinson's disease: a case-control study in southeastern Sweden

Abstract: PURPOSE AND METHODS: To investigate the possible impact of nutritional and environmental risk factors for idiopathic Parkinson's disease (IP), a case-control study was performed in the county of Os ...

Circadian rhythm of periodic limb movements and sensory symptoms of restless legs syndrome

Abstract: The symptoms of restless legs syndrome (RLS) worsen while patients are sitting or lying and also worsen at night. The current study was designed to determine if the periodic limb movements (PLMs) and sensory symptoms of RLS are modulated by an independent circadian factor. We recorded sleeping and waking PLMs and waking sensory symptoms in eight volunteers with RLS for 3 successive nights and days, starting with a polysomnographic recording of 2 nights, followed by a third night of sleep deprivation and the day after sleep deprivation. This study showed that both the PLMs and sensory symptoms were worst at night with a maximum for both between midnight and 1:00 AM and a minimum between 9:00 and 11:00 AM. Sleep and drowsiness had a tendency to worsen PLMs and sensory symptoms after the night of sleep deprivation. Circadian temperature curves were normal in all four patients with adequate data collection. The highest PLM counts occurred on the falling phase of the circadian temperature curve whereas the lowest PLM counts occurred on the rising phase of the curve. We conclude that the PLM and sensory symptoms in RLS are influenced by a circadian rhythm, and that the "worsening at night" criterion of the RLS Definition Criteria is, at least in part, distinct from the "worsening while lying or sitting" criterion.

Melatonin as a therapy in REM sleep behavior disorder patients: an open-labeled pilot study on the possible influence of melatonin on REM-sleep regulation.

Abstract: REM sleep behavior disorder (RBD) is clinically impressive by virtue of its vigorous sleep behaviors usually accompanying vivid, striking dreams. The main feature of the disorder, REM sleep without muscle atonia, has been shown in a variety of diseases; therefore, the disorder might possibly be underestimated. In an open-labeled trial, we treated six consecutive RBD patients over a 6-week period with 3 mg melatonin given within 30 minutes before bedtime. There was a dramatic clinical improvement in five of the six patients within a week which extended beyond the end of treatment for weeks or months. A second polysomnogram performed 6 weeks after the beginning of treatment showed a significant tendency toward normalization of the percentage of REM sleep, a significant reduction of 30-second epochs, scored as REM sleep without muscle atonia, a significant reduction of stage-shifts in REM, and a significant reduction in epochs considered as movement time in REM. All other sleep parameters were not changed consistently. We hypothesize that internal desynchrony might be a part of the underlying pathophysiology in RBD. Our data might give first evidence to the hypothesis that exogenous melatonin, administered to patients with internal desynchrony at the time of the maximal rise of melatonin secretion, might increase the overall amplitude of the circadian pacemaker by reentraining the suprachiasmatic nucleus and thereby restore circadian driven rhythms, one of them being the circadian modulation of REM sleep.

Camptocormia (bent spine) in patients with Parkinson's disease--characterization and possible pathogenesis of an unusual phenomenon.

Abstract: Camptocormia is characterized by severe forward flexion of the thoracolumbar spine which increases while walking and disappears in the recumbent position. We describe for the first time eight patients with presumed idiopathic Parkinson's disease (mean age 66+/-5 yrs; mean symptom duration 13.1+/-5.1 yrs) who developed camptocormia. This impressive abnormal posture emerged 4-14 years from disease onset, and in some patients stooped posture was the prominent symptom at diagnosis. There was no clear correlation between camptocormia and levodopa treatment. In some patients the camptocormic posture improved, and in others it was unchanged or even aggravated following levodopa administration. Three patients reported worsening of this symptom during "off" periods and also with fatigue. The pathogenesis of this phenomenon is unknown but might represent either a rare type of dystonia or an extreme form of rigidity.

Advantages of a modified scoring method for the Rush Video-Based Tic Rating Scale.

Abstract: Previously, we published a video-based objective rating scale of tics that met reliability and validity criteria for measurement of five domains of tic disability. In the original form, the scale's metric properties did not permit internal comparison of each of the five domains of impairment and did not provide a total score for use as a primary outcome measure. In this study, we retained the original scale and videotape protocol but tested whether a modified scoring system corrected these limitations. The new scoring method rated assigned tic data to ratings of 0-4 on five disability categories: number of body areas, frequency of motor tics, frequency of phonic tics, severity of motor tics, and severity of phonic tics. The sums of these ratings yielded a total score of overall tic disability (0-20). In a series of 31 patients with Gilles de la Tourette syndrome, we assessed Spearman correlation coefficients for the old and new scoring systems as well as the correlation of the new ratings with the objectively derived sections of the Yale Global Tic Severity Scale (YGTSS), another valid and reliable scale used in clinical practice and research. For each domain, the rank order for the scores on the original scale was well retained in the new scores. Likewise, for each domain, ranking with the new scoring system correlated well with scores on the comparable objective item from the YGTSS. The new total score accurately captured the rank order of the combined five domains from the original scale and correlated well with the total objective motor plus phonic tic score from the YGTSS and the YGTSS Tourette Syndrome Overall Impairment Rating. These data demonstrate that the modified videotape-based scoring system retains the essential information gathered in the original Rush scale. The modification provides comparisons among the five assessed domains and a total objectively based disability score that can be used as a single outcome measure for assessing tic disability.

Pathophysiology of chorea and bradykinesia in Huntington's disease

Abstract: This article reviews the neurophysiological abnormalities described in Huntington's disease. Among the typical features of choreic movements are variable and random patterns of electromyographic (EMG) activity, including cocontraction of agonist and antagonist muscles. Studies of premotor potentials show that choreic movements are not preceded by a Bereitschaftspotential, therefore demonstrating that choreic movement is involuntary. Early cortical median-nerve somatosensory-evoked potentials have reduced amplitudes and the reduction correlates with reduced glucose consumption in the caudate nucleus. Long-latency stretch reflexes evoked in the small hand muscles are depressed. These findings may reflect failed thalamocortical relay of sensory information. In Huntington's disease, the R2 response of the blink reflex has prolonged latencies, diminished amplitudes, and greater habituation than normal. These abnormalities correlate with the severity of chorea in the face. Patients with Huntington's disease perform simple voluntary movements more slowly than normal subjects and with an abnormal triphasic EMG pattern. Bradykinesia is also present during their performance of simultaneous and sequential movements. Eye movements show abnormalities similar to those seen in arm movements. In Huntington's disease, arm movement execution is associated with reduced PET activation of cortical frontal areas. Studies using transcranial magnetic stimulation show that patients with Huntington's disease have normal corticospinal conduction but some patients have a prolonged cortical silent period. Bradykinesia results from degeneration of the basal ganglia output to the supplementary motor areas concerned with the initiation and maintenance of sequential movements. The coexisting hyperkinetic and hypokinetic movement disorders in patients with Huntington's disease probably reflect the involvement of direct and indirect pathways in the basal ganglia-thalamus-cortical motor circuit.

Animal models of tremor

Abstract: Animal models of tremor have been widely used in experimental neurology, because they are an indispensable requirement for understanding the pathophysiology of human tremor disorders and the development of new therapeutic agents. This review focuses on three approaches to produce tremor in animals (application of tremorgenic drugs, experimental central nervous system lesions, study of genetic mutants) and their use in simulating tremor syndromes of humans. Whereas harmaline induces a postural/kinetic tremor in animals that shares some features with human essential tremor/enhanced physiological tremor, MPTP tremor is the best model available for rest tremor in people. The tremor following experimental lesion of the ventromedial tegmentum in primates closely resembles Holmes tremor in humans, whereas cerebellar intention tremor is mimicked by cooling of the lateral cerebellar nuclei. The "campus syndrome," discovered in a breed of Pietrain pigs, might be a useful model of human orthostatic tremor. However, no animal model has yet been generated that exactly recreates all features of any of the known tremor disorders in humans. Problems encountered when comparing tremor in animals and humans include differing tremor frequencies and the uncertainty, if specific transmitter abnormalities/central nervous system lesions seen in animal tremor models are characteristic for their human counterparts. The search for adequate tremor models continues.

Hallucinations, sleep fragmentation, and altered dream phenomena in Parkinson's disease

Abstract: In a series of consecutively randomized outpatients who had Parkinson's disease (PD), we examined the association of three behaviors: sleep fragmentation, altered dream phenomena, and hallucinations/illusions. Using a log-linear model methodology, we tested the independence of each behavior. Sixty-two percent of the subjects had sleep fragmentation, 48% had altered dream phenomena, and 26% had hallucinations/illusions. Eighty-two percent of the patients with hallucinations/illusions experienced some form of sleep disorder. The three phenomena were not independent. The interaction between sleep fragmentation and altered dream phenomena was strongly statistically significant. Likewise, a significant interaction existed between altered dream phenomena and hallucinations/illusions. No interaction occurred between sleep fragmentation and hallucinations/illusions. Sleep fragmentation, altered dream phenomena, and hallucinations/illusions in PD should be considered distinct but often overlapping behaviors. The close association between altered dream phenomena and hallucinations suggests that therapeutic interventions aimed at diminishing dream-related activities may have a specific positive impact on hallucinatory behavior.

Quetiapine for the treatment of drug-induced psychosis in Parkinson's disease.

Abstract: Quetiapine is an atypical antipsychotic with clozapine-like pharmacology but without associated agranulocytosis. We report our complete experience with quetiapine for the treatment of drug-induced psychosis (DIP) in Parkinson's disease (PD). Thirty-five patients with PD and DIP aged 75 years (range, 58-89) with a mean PD duration of 8.4 years on an average of 427 mg levodopa per day received a mean dose of 40.6 mg quetiapine daily. Twenty of 24 neuroleptic-naive patients reported marked improvement of psychosis without a decline in motor function as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS-motor). Ten patients had a baseline and 4-week follow-up assessment using the Mini-Mental Status Examination (MMSE) and Brief Psychiatric Rating Scale (BPRS). The improvement in BPRS score (32.6 versus 22.8) was clinically and statistically significant (p = 0.024). Three of 24 were unable to tolerate quetiapine because of orthostatic hypotension, headache, nausea, and persistence of hallucinations. One patient died of an unrelated cause. We also tried to switch 11 psychiatrically stable patients on clozapine (eight) and olanzapine (three). Five patients made this transition without a loss of effect as measured on BPRS and MMSE. Six did not (five on clozapine, one on olanzapine) because of confusion, erratic behavior, and increased hallucinations. No crossover failure had worsened PD except for increased tremor in one. Quetiapine is useful and well-tolerated as a first drug to treat DIP in PD but must be used cautiously to replace other atypical antipsychotic drugs.

Positron emission tomographic studies in restless legs syndrome.

Abstract: We studied six restless legs syndrome (RLS) patients with [F18]fluorodeoxyglucose (FDG) positron emission tomography (PET). We also studied four of these same patients with [F18]fluorodopa (FDOPA) PET. The patients' FDG and FDOPA PET scans were compared with those from age-matched healthy control subjects. No significant differences between the two groups were found for any regional blood flow values derived from the FDG scans or for any binding constants derived from the FDOPA scans. These results suggest that any abnormal resting brain metabolic activity or putative presynaptic dopaminergic defect in RLS is likely either to be so subtle that it is below the threshold for ready detection by PET or that it is located in an area of neural tissue inaccessible to the current scanner. No substantial defect is likely to involve the dopaminergic nigrostriatal axis.

Catatonia as a psychomotor syndrome: a rating scale and extrapyramidal motor symptoms.

Abstract: BACKGROUND Catatonia was first described by Kahlbaum as a psychomotor disease with motor, behavioral, and affective symptoms. In keeping with this concept, we developed a rating scale for catatonia (Northoff Catatonia Scale [NCS]) with three different categories of symptoms (i.e., motor, behavioral, affective). Furthermore, the question of the relationship among catatonic symptoms, extrapyramidal motor symptoms, and neuroleptics was addressed in the present study. METHOD 34 acute catatonic patients and 68 age-, sex-, diagnosis-, and medication-matched psychiatric control subjects were investigated on days 0, 1, 3, 7, and 21 with the NCS, with other already validated catatonia rating scales by Rosebush, Bush (BFCRS), and Rogers (MRS), as well as with scales for hypokinetic (SEPS) and dyskinetic (AIMS) extrapyramidal motor features. Validity and reliability of the new scale, factor analysis, correlational analysis, and differences between catatonic patients and psychiatric control subjects were statistically calculated. RESULTS NCS showed high validity (i.e., significant positive correlations [p <0.0001] with the other scales, significant differences between catatonic and control subjects), high intra- and interrater reliabilities (r = 0.80–0.96), and high affective subscores. Factor analysis revealed four factors best characterized as affective, hypoactive, hyperactive, and behavioral. Catatonic scores in NCS correlated significantly with AIMS on day 0 and SEPS on days 7 and 21. There were no significant differences in catatonic (i.e., NCS, MRS, BFCRS) and extrapyramidal (i.e., AIMS, SEPS) scores between neuroleptically treated and untreated catatonic subjects. CONCLUSIONS The following conclusions were drawn: (1) the NCS has to be considered as a valid and reliable rating instrument for catatonia; (2) catatonia can be characterized by psychomotor symptoms encompassing motor, affective, and behavioral alterations; and (3) extrapyramidal hyperkinesias like dyskinesias are apparently closely related to catatonic symptoms which, in general, seem to be relatively independent of previous neuroleptic medication.

Progression of falls in postmortem-confirmed parkinsonian disorders.

Abstract: Although falls are known to occur in several parkinsonian disorders, such as Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy bodies (DLB), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP), differences in the evolution of this feature have not been studied systematically in pathologically confirmed cases. Seventy-seven cases with pathologically confirmed parkinsonian disorders (PD: n = 11, MSA: n = 15, DLB: n = 14, CBD: n = 13, PSP: n = 24), collected up to 1994, formed the basis for a multicenter clinicopathologic study organized by the National Institute of Neurological Disorders and Stroke to improve differential diagnosis of parkinsonian disorders. In the present study, we determined the time course, that is, the duration from first symptom to onset (latency) and duration from onset to death, of recurrent falls. Furthermore, we analyzed the diagnostic validity of a predefined latency to onset of recurrent falls within 1 year of symptom onset. Significant group differences for latency, but not duration, of recurrent falls were observed. Latencies to onset of falls were short in PSP patients, intermediate in MSA, DLB, and CBD, and long in PD. Recurrent falls occurring within the first year after disease onset predicted PSP in 68% of the patients. Our study demonstrates for the first time that latency to onset, but not duration, of recurrent falls differentiates PD from other parkinsonian disorders. Whereas early falls are important for the diagnosis of PSP, the addition of other features increases its diagnostic predictive value.

Dietary factors in Parkinson's disease: The role of food groups and specific foods

Abstract: PURPOSE The association between self-reported past food intake and Parkinson's disease (PD) was investigated in a case-control study of men and women aged 40–89 years METHODS Newly diagnosed idiopathic PD cases were ascertained from neurologists, and from outpatient and pharmacy computerized databases, at the Group Health Cooperative (GHC) clinics in the Puget Sound region of Washington state Control subjects were chosen from the GHC patient roster and had no reported history of diagnosed neurodegenerative disease Dietary data were obtained from structured questionnaires RESULTS An increase in PD risk with increasing intake was noted for foods that contain animal fat and foods containing vitamin D Intake of fruits, vegetables, meats, bread and cereals, or foods containing vitamins A, C, E, or iron was not significantly related to PD risk Vitamin use, in general, was also not found to be related to PD risk, although a significant trend of increasing risk of PD was noted for intake of vitamin A supplements CONCLUSIONS Although these data support previous findings of no association of past intake with most food groups and PD risk, they confirm an increased risk of PD associated with foods containing animal fat

A data-driven approach to the study of heterogeneity in idiopathic Parkinson's disease: identification of three distinct subtypes.

Abstract: Idiopathic Parkinson's disease (IPD) has been subclassified on the basis of predominant motor symptomatology, age at disease onset, depressive affect, and cognitive performance. However, subgroups are usually arbitrarily defined and not reliably based on qualitatively distinct neuropathology. We explored heterogeneity in IPD in a data-driven manner using comprehensive demographic, motor, mood, and cognitive information collected from 176 patients with IPD. Cluster analysis revealed three subgroups of patients at a disease duration of 5.6 years and two subgroups at 13.4 years. The subgroups may represent the clinical progression of three distinct subtypes of IPD. The "motor only" subtype was characterized by motor symptom progression in the absence of intellectual impairment. Equivalent motor symptom progression was shown by the "motor and cognitive" subtype which was accompanied by executive function deficits progressing to global cognitive impairment. The "rapid progression" subtype was characterized by an older age at disease onset and rapidly progressive motor and cognitive disability. There was no relationship between the motor and cognitive symptoms in any subtype of IPD. We conclude that the clinical heterogeneity of IPD is governed by distinct neuropathologic processes with independent etiologic influences.

Persistent Sydenham's chorea.

Abstract: BACKGROUND Sydenham's chorea (SC) occurs in 26% of patients with rheumatic fever (RF). Despite usually being described as a self-limited condition, few reports indicate that SC may persist in rare subjects. OBJECTIVE To investigate the proportion of subjects with SC lasting more than 2 years and if clinical features differentiate patients with SC with a duration of less than 2 years (Group 1) from those with SC lasting more than 2 years (Group 2). METHODS Prospective assessment of all patients with SC seen at our service from July 1993 through March 1998 analyzing the following: gender; age at onset; frequency of arthritis, carditis, family history of RF and SC; topographic distribution; and chorea severity on a 0–4 scale. RESULTS Thirty-two patients (19 female, 13 male) were studied. In Group 1 (16 subjects, 50%) the follow-up period was 36.2 ± 20.0 months; 50% were female; age at onset was 10.9 ± 2.6 years; arthritis and carditis were present in 37.5% and 31.2%, respectively; family history of SC was reported by 18.7%; hemichorea was seen in 25.8% of subjects; and the mean intensity of chorea was 2.60.8. In Group 2, with a follow-up period of 34.1 ± 18.9 months, 68.8% were female; age at onset was 9.3 ± 3.9 years; arthritis and carditis were diagnosed in 18.7% and 50%, respectively; no patient reported a family history of SC; hemichorea was observed in 6.2% of subjects; and the mean intensity of chorea was 2.8 ± 0.5. No difference was statistically significant. CONCLUSIONS SC persists in half of our patients. Female gender, possibly related to endocrine factors, as well as the presence of carditis, indicating a more severe disease, may be risk factors for a longer duration of SC.

The α2‐adrenergic receptor antagonist idazoxan reduces dyskinesia and enhances anti‐parkinsonian actions of L‐dopa in the MPTP‐lesioned primate model of Parkinson's disease

Abstract: Dopamine replacement therapy in patients with Parkinson's disease is plagued by the emergence of abnormal involuntary movements known as L-dopa-induced dyskinesias. It has been demonstrated that yohimbine can reduce L-dopa-induced dyskinesia in the MPTP-lesioned primate model of Parkinson's disease. Yohimbine is, among other things, an alpha-adrenergic receptor antagonist. In this study, we demonstrate that the selective and potent alpha2-adrenergic receptor antagonist idazoxan reduces L-dopa-induced dyskinesia in the MPTP-lesioned marmoset model of Parkinson's disease. The alpha2-adrenergic receptor antagonists rauwolscine and yohimbine also reduce L-dopa-induced dyskinesia. Furthermore, we demonstrate that coadministration of idazoxan with L-dopa can provide an anti-parkinsonian action more than twice the length of that seen with L-dopa alone. However, idazoxan as a monotherapy displayed no anti-parkinsonian actions. We propose that idazoxan in combination with L-dopa may provide a novel approach to the treatment of Parkinson's disease that will not only reduce the dyskinetic side effects, but extend the anti-parkinsonian actions of L-dopa. Idazoxan, as an adjunct to dopamine replacement, may prove useful in the treatment of parkinsonian patients at all stages of disease progression.

Efficacy of unilateral deep brain stimulation of the VIM nucleus of the thalamus for essential head tremor.

Abstract: Essential tremor is a common movement disorder. Deep brain stimulation of the VIM nucleus of the thalamus has been reported to be efficacious for reducing essential hand tremor. The effect of deep brain stimulation of the thalamus on essential head tremor has not been well studied. Therefore, we evaluated the effect of DBS of the thalamus in 38 patients with essential head tremor. Head tremor scores prior to surgery were compared with scores at 3, 6, and 12 months postimplant with stimulation "on" and "off." The 3-month evaluations were blinded for 24 patients and all others were open-label. There was a significant improvement in head tremor at all postimplant evaluations compared with baseline. Essential head tremor can be reduced with deep brain stimulation of the VIM nucleus of the thalamus and, pending the results of other controlled trials, should be considered as a treatment option for patients with disabling essential head tremor unresponsive to medication.

Effect of treatment with L‐dopa/carbidopa or L‐selegiline on striatal dopamine transporter SPECT imaging with [123I]β‐CIT

Abstract: The effect of subchronic treatment with L-dopa/carbidopa or L-selegiline on striatal dopamine transporters (DAT) was examined in patients with idiopathic Parkinson's disease with SPECT (single photon emission computed tomography) using [123I]beta-CIT (2beta-carbomethoxy-3beta-[4-iodophenyl]tropane) as the radiotracer. Patients who were not currently being treated with these medications were given either 750 mg L-dopa/carbidopa per day (n = 8) or 10 mg L-selegiline per day (n = 8). [123I]beta-CIT imaging was performed three times in each patient: at baseline before treatment, while on medication and after 4-6 weeks of drug treatment, and following withdrawal from medication (approximately 1 week for L-dopa/carbidopa and 9 weeks for L-selegiline). Comparison of scans 2 and 3 provided a measure of drug occupancy of the [123I]beta-CIT binding site; comparison of scans 1 and 2 provided a measure of both up- or downregulation of DAT levels and drug occupancy following subchronic drug treatment. DAT levels were assessed from an image acquired approximately 22 hours after radiotracer injection as a ratio of regional brain activities: (striatum - occipital)/occipital. Striatal DAT levels were not significantly different when any two of the three scans were compared for both drug treatments. These results suggest that typical clinical doses of L-dopa/carbidopa and L-selegiline do not induce significant occupancy of the [123I]beta-CIT binding site and that 4-6 weeks of treatment causes no significant modulation of DAT levels. These results support the validity of measuring DAT levels with [123I]beta-CIT without the need to withdraw patients from medication treatment.

Riluzole therapy in Huntington's disease (HD).

Abstract: We conducted a 6-week open-label trial of riluzole (50 mg twice a day) in eight subjects with Huntington's disease. Subjects were evaluated before riluzole treatment, on treatment, and off treatment with the chorea, dystonia, and total functional capacity (TFC) scores from the Unified Huntington's Disease Rating Scale and magnetic resonance spectroscopy measurements of occipital cortex and basal ganglia lactate levels. Adverse events and safety blood and urine tests were assessed throughout the study. All subjects completed the study and riluzole was well tolerated. The age was 45+/-10.2 years (mean +/- standard deviation) and the disease duration was 6.1+/-4.1 years. The chorea rating score improved by 35% on treatment (p = 0.013) and worsened after discontinuation of treatment (p = 0.026). There were no significant treatment effects on the dystonia or TFC scores. The baseline occipital and basal ganglia lactate levels were elevated in all subjects; there was a trend toward lower lactate/creatine ratios during riluzole treatment in the basal ganglia spectra but not in occipital cortex spectra. Additional clinical studies of riluzole for both symptomatic and neuroprotective benefit in Huntington's disease are warranted.

Ropinirole for restless legs syndrome.

Abstract: Restless legs syndrome (RLS) is a common and underdiagnosed condition that results in a desire to move the extremities often associated with paresthesia/dysesthesia, motor restlessness, worsening of symptoms at rest with at least temporary relief by activity, and worsening of symptoms in the evening or night. We tested the new dopamine agonist ropinirole in 16 patients with RLS in an open-label trial. The mean daily dose was 2.8+/-2.3 mg (range, 0.5-12.0). The 13 patients who completed the study reported a 58.7% improvement (p = 1.08 x 10(-8)) as judged by the abbreviated International Restless Legs Study Group questionnaire. Three patients discontinued the medication secondary to adverse events (rash and nervousness) and other extenuating circumstances. These encouraging preliminary results justify larger and more controlled trials of ropinirole in patients with RLS.

Velocity modulation and rhythmic synchronization of gait in Huntington's disease

Abstract: This study analyzed the ability of patients with Huntington's disease (HD) to modulate gait velocity without external sensory cues and in response to an auditory rhythmic cue within a frequency entrainment design. Uncued gait patterns of 27 patients were first assessed during normal, slower, and faster self-paced walking. During rhythmic trials, metronome and musical beat patterns were delivered at rates 10% slower and 10-20% faster than baseline cadence to cue gait patterns. After the rhythmic trials, patients were retested at normal gait speed without rhythm. Gait velocities in the patients with HD were below normal reference values in all ranges. Patients were able to significantly (p <0.05) modulate their gait velocity during self-paced and rhythmic metronome cueing but not during music. The ability to modulate gait velocity was retained regardless of the severity of the disease. Gait velocity declined with an increase in disability and chorea score. The disability score differentiated better between gait velocity of moderately and severe patients than chorea score. Slowness of gait was significantly correlated only with disability score and not with chorea. Patients had more difficulty producing adequate step rates than stride lengths during normal and fast walking speeds. After the rhythmic trials, unpaced gait velocity remained significantly (p <0.05) higher than baseline. This carry-over effect was not seen after the uncued trials. Synchronization ability was deficient in all patients, deteriorated with severity of disease, and was already compromised in patients with soft disease signs. Rhythmic tracking of music declined more with severity of disease than metronome tracking. In summary, patients were able to modulate velocity with and without external cues. Velocity adaptations to the external rhythm in music and metronome were achieved without exact synchronization between step cadence and rhythmic stimulus.

Punding on L-dopa.

Abstract: "Punding" is a stereotypical motor behavior in which there is an intense fascination with repetitive handling and examining of mechanical objects, such as picking at oneself or taking apart watches and radios or sorting and arranging of common objects, such as lining up pebbles, rocks, or other small objects. It is thought to be dopamine-related although only a single report of punding in a patient with Parkinson's disease (PD) resulting from L-dopa has been reported. We describe three additional cases. All were women aged 65-72 years with a PD duration between 10 and 20 years, on 500-1900 mg L-dopa per day. One spent hours in the market fascinated by cans. At home she endlessly examined and catalogued her jewelry. Another picked threads in rugs indoors and weeded her garden compulsively to the point of wetting herself rather than stopping. The third hoarded flashlights taking them apart and reassembling them. All improved with reduction of their anti-PD medications. We think punding is an uncommon but overlooked complication of dopaminergic drugs.

Studies of penetrance and anticipation in five autosomal-dominant restless legs syndrome pedigrees.

Abstract: Restless legs syndrome (RLS) can occur with an autosomal-dominant mode of inheritance. To determine if there are distinguishing features of RLS pedigrees which might clarify molecular mechanisms of pathogenesis, five pedigrees with 81 affected members were analyzed for age of onset, sex ratio, and transmission pattern. One-factor analysis of variance of ages of onset between generations was carried out, and segregation ratios were calculated for each generation. These kindreds showed an autosomal-dominant mode of inheritance and a male:female ratio of 1:1.4 (p = 0.15). One of the five analyzed pedigrees shows some evidence of reduced penetrance. In two of the five analyzed pedigrees, there is statistical support for anticipation (p<0.05). These variations in penetrance and anticipation suggest possible genetic heterogeneity.

Movement-related potentials in Parkinson's disease: external cues and attentional strategies.

Abstract: Hypokinetic movement can be greatly improved in Parkinson's disease patients by the provision of external cues to guide movement. It has recently been reported, however, that movement performance in parkinsonian patients can be similarly improved in the absence of external cues by using attentional strategies, whereby patients are instructed to consciously attend to particular aspects of the movement which would normally be controlled automatically. To study the neurophysiological basis of such improvements in performance associated with the use of attentional strategies, movement-related cortical potentials were examined in Parkinson's disease and control subjects using a reaction time paradigm. One group of subjects were explicitly instructed to concentrate on internally timed responses to anticipate the presentation of a predictably timed go signal. Other subjects were given no such instruction regarding attentional strategies. Early-stage premovement activity of movement-related potentials was significantly increased in amplitude and reaction times were significantly faster for Parkinson's disease subjects when instructed to direct their attention toward internally generating responses rather than relying on external cues. It is therefore suggested that the use of attentional strategies may allow movement to be mediated by less automatic and more conscious attentional motor control processes which may be less impaired by basal ganglia dysfunction, and thereby improve movement performance in Parkinson's disease.

Apomorphine protects against MPTP-induced neurotoxicity in mice.

Abstract: R-apomorphine is a potent radical scavenger and iron chelator. The neuroprotective property of R-apomorphine, a dopamine D1-D2 receptor agonist, has been studied in the MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) model of Parkinson's disease. Pretreatment with 5-10 mg/kg R-apomorphine administered subcutaneously in C57BL mice protects against MPTP (24 mg/kg administered intraperitoneally) induced loss of nigrostriatal dopamine neurons as indicated by striatal dopamine content, tyrosine hydroxylase content, and tyrosine hydroxylase activity. In vitro, R-apomorphine inhibited mice striatal MAO-A and MAO-B activities with IC50 values of 93 microM and 241 microM. It is suggested that the neuroprotective effect of R-apomorphine against MPTP neurotoxicity derives from its radical scavenging and MAO inhibitory actions and not from its agonistic activity because the mechanism of MPTP dopaminergic neurotoxicity involves the generation of oxygen radical species-induced oxidative stress.