Search

Purpose: Falls are a major problem and cause poor quality of life and reduced life expectancy in people affected by Parkinson's disease (PD). The timed up-and-go (TUG) test is the most popular test of walking ability in patients with PD. However, it carries a risk of falls because patients are told to walk as quickly as possible. The purpose of this study was to characterise issues of safety and reproducibility arising in TUG tests., Methods: Our population was 7 hospitalised patients (4 men, 3 women) with PD and 1 healthy control. We used video capture, Motion Analyser software, and an innovative Yorisoi (snuggling nursing robot) robot., Results: We found the same movements when patients walked in time to a verbal rhythm provided by the physiotherapist and when they used the robot in walking. The TUG times were longest when the therapist provided no intervention. The typical PD patient experienced freezing of gait when rounding the reflective cone marker in the TUG test, and after turning, experienced gait festination. The patient thus encountered difficulty in using the reflective marker. Moreover, because of the characteristic PD shuffling gait, the patient's steps were difficult to count automatically. After the turn, the patient's body leaned heavily; however, if the physiotherapist or the robot applied a light force in the direction of the positive axis, it was possible to prevent a fall., Conclusions: When applied to patients with PD, the TUG test requires modifications for safety and more accurate step counting to improve reproducibility.IMPLICATIONS FOR REHABILITATIONThe presence of a sense of security with the attendant or the robot is related to walking speed.The TUG test must be reproducible in patients with PD, regardless of whether there is a rhythm or an attendant, and must be able to count the steps in a shuffling gait.The TUG test must consider safety in patients with PD, because it is easier to fall after a turn and when sitting on a chair, and it is instructed to be in hurry walk.After making a turn, a patient's body may lean heavily; however, if a physiotherapist or a Yorisoi (snuggling nursing robot) robot applies a light force in the direction of the positive axis, it is possible to prevent a fall.Assertive technology, such as the Yorisoi robot, may be used to improve the safety TUG test in patients with PD.

The differential diagnosis of Parkinson's disease and multiple system atrophy can be challenging, especially in the early stages of the diseases. We developed a proteomic profiling strategy for parkinsonian diseases using mass spectrometry analysis for magnetic-bead-based enrichment of cerebrospinal fluid peptides/proteins and subsequent multivariate statistical analysis. Cerebrospinal fluid was obtained from 37 patients diagnosed with Parkinson's disease, 32 patients diagnosed with multiple system atrophy, and 26 patients diagnosed with other neurological diseases as controls. The samples were from the first cohort and the second cohort. Cerebrospinal fluid peptides/proteins were purified with C8 magnetic beads, and spectra were obtained by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Principal component analysis and support vector machine methods are used to reduce dimension of the data and select features to classify diseases. Cerebrospinal fluid proteomic profiles of Parkinson's disease, multiple system atrophy, and control were differentiated from each other by principal component analysis. By building a support vector machine classifier, 3 groups were classified effectively with good cross-validation accuracy. The model accuracy was well preserved for both cases, training by the first cohort and validated by the second cohort and vice versa. Receiver operating characteristics proved that the peak of m/z 6250 was the most important to differentiate multiple system atrophy from Parkinson's disease, especially in the early stages of the disease. A proteomic pattern classification method can increase the accuracy of clinical diagnosis of Parkinson's disease and multiple system atrophy, especially in the early stages., (Copyright © 2012 Movement Disorder Society.)

Caffeine is a nonselective competitive blockade of adenosine A1 and A2A receptors. In this report, we studied the efficacy of 100 mg of caffeine per day on the freezing of gait (FOG) for patients with Parkinson's disease. Different subtypes of FOG showed different therapeutic responses to caffeine. Caffeine improved "total akinesia" type of FOG, but had no effect on "trembling in place." Tolerance developed to the beneficial effect of caffeine on FOG within a few months, but a 2-week caffeine withdrawal period could restore the effect of caffeine.

We analyzed two disease model groups with rats infected by Japanese encephalitis virus (JEV), a 90-day group and a 180-day group after JEV infection. The time measured by the modified pole test showed that motor activities in these two groups were slower than those of age-matched control groups. Striatal dopamine (DA) levels were significantly decreased in all JEV-infected rats. Norepinephrine concentration in brain regions in the 180-day group was significantly decreased in the medulla oblongata and hypothalamus as compared with the control and 90-day group. Tyrosine hydroxylase-positive neurons were significantly decreased in both JEV-infected rat groups. These results suggest that DA decrease and pathological changes in JEV-infected model rats persist for a long time, at least up to 180 days, and this model will be useful for the evaluation of new anti-parkinsonian agents.

Objectives: We hypothesize that the regional pattern of blood flow reduction in the brain is different between tremor-dominant Parkinson's disease (PD) and postural instability gait difficulty (PIGD)-dominant PD. We therefore investigated the association of phenotypes in untreated PD with brain perfusion on SPECT using three-dimensional stereotactic surface projection (3D-SSP) technique., Patients and Methods: Thirty-three patients who had PD without dementia (12 men and 21 women with a mean age of 67.1+/-6.4 years) were included in this study. Their symptoms were rated using the Unified Parkinson's Disease Rating Scale (UPDRS). Patients were grouped in two phenotypes: tremor and PIGD-dominant groups based on UPDRS components. Around the same time, all patients were examined by N-isopropyl-p[123I] iodoamphetamine single photon emission computed tomography (123I-IMP SPECT), and obtained images were analyzed with 3D-SSP using an image-analysis software, NEUROSTAT. Data on brain surface perfusion extracted by 3D-SSP analysis were compared between the PD patients and the normal control group. The same comparisons were made for subgroups of PD patients., Results: Cerebral perfusion was decreased at the anterior cingulate cortex and primary visual cortex of the PD patients, and especially by the pixel-by-pixel comparison, perfusion was significantly decreased at the right anterior cingulate cortex compared with the normal controls. In the PIGD-dominant group, more severe hypoperfusion was seen at the same regions. In the tremor-dominant group, significant hypoperfusion was not seen compared with the normal controls., Conclusions: The regional pattern of blood flow reduction in the brain was found to be different between tremor-dominant PD and PIGD-dominant PD. These regional differences were considered to suggest different and disease-specific combinations of underlying pathophysiological and neurochemical processes.

Objective: The aim of the present study is to investigate the association of symptoms in Parkinson's disease (PD) with cerebral perfusion on single photon emission computed tomography (SPECT). The clinical features of PD were compared with SPECT images of the brain obtained by three-dimensional stereotactic surface projection (3D-SSP) analysis., Patients and Methods: Thirty-eight patients who had PD without dementia (17 men and 21 women with a mean age of 68.6 +/- 4.7 years) were enrolled in this study. Their symptoms were rated using the unified Parkinson's disease rating scale (UPDRS). Within a week, all patients were examined by SPECT with 1-123, and reconstructed images were analyzed with 3D-SSP using an image-analysis software, iSSP ver. 3.5. Data on brain surface perfusion extracted by 3D-SSP analysis were compared between the PD patients and the normal control group. The same comparisons were made for subgroups of PD patients with severe symptoms, such as tremor, gait disturbance, bradykinesia, and the UPDRS motor score., Results: Cerebral perfusion was decreased at the anterior cingulate cortex and occipital lobe of the PD patients compared with the normal controls. In the subgroups with severe gait disturbance and severe bradykinesia, additional hypoperfusion was seen at the lateral frontal association and lateral temporal association and the medial frontal gyrus, and by the pixel-by-pixel comparison, perfusion was significantly decreased (p < 0.05) at the medial frontal gyrus and anterior cingulate cortex compared with the normal control group., Conclusion: In PD patients, severe gait disturbance and bradykinesia may be correlated with hypoperfusion of the medial aspect of the frontal lobe. This suggests that functional disturbance of the supplementary motor area and other parts of the frontal lobe are involved in the development of gait disturbance and bradykinesia in PD.

A single dose of isatin (indole-2,3-dione)(i.p.), an endogenous MAO inhibitor, significantly increased norepinephrine and 5-hydroxytryptamine concentrations in the rat brain and also significantly increased acetylcholine and dopamine (DA) levels in the rat striatum. Urinary isatin concentrations in patients with Parkinson's disease tend to increase according to the severity of disease. We have developed a rat model of Parkinson's disease induced by the Japanese encephalitis virus (JEV). The distribution of the pathological lesions of JEV-rats resemble those found in Parkinson's disease. Significant behavioral improvement was observed in JEV-rats after isatin, L-DOPA and selegiline administration using a pole test. Both isatin and selegiline prevented the decrease in striatum DA levels of JEV-rats. The increased turnover of DA (DOPAC/DA) induced by JEV was significantly inhibited by isatin, but not selegiline. These findings suggest that JEV-infected rats may serve as a model of Parkinson's disease and that exogenously administered isatin and selegiline can improve JEV-induced parkinsonism by increasing DA concentrations in the striatum.

Objective: To investigate the efficacy and the rate of adverse events of chronic low-dose levodopa-carbidopa therapy in Japanese patients with Parkinson's disease (PD)., Patients and Methods: A total of 92 Japanese PD patients treated with low doses of levodopa from the outset were studied. Both disease-specific motor disabilities and quality of life (QOL) in the patients were evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) and the Parkinson's Disease 39 Quality of Life Questionnaire (PDQ39), respectively., Results: In the overall patient group, the mean duration of treatment, the mean daily dose of levodopa, the disability scores and the motor scores of UPDRS were 6.2 years, 186.4 mg, 8.0 and 19.2, respectively. The rates of motor fluctuations, dyskinesias and hallucinations were 8.7%, 6.5% and 14.1%, respectively. The mean summary index of PDQ39 scores was 23.1. Patients with motor fluctuations showed a significantly earlier disease onset. Dose of levodopa, age at onset, and treatment duration were not associated with the occurrence of dyskinesias. Patients with hallucination had higher doses of levodopa and dopamine agonist., Conclusions: Our results demonstrate that chronic administration of a low-dose levodopa preparation can provide satisfactory benefit with a low incidence of motor complications, and can result in good QOL in Japanese patients with PD. The concomitant use of a small amount of dopamine agonist and amantadine from the outset has partly contributed to a reduced dose of levodopa and the lesser occurrence of motor complications.

Objectives: Cerebral blood flow was compared among patients with dementia with Lewy bodies (DLB), Parkinson's disease with dementia (PDD), Parkinson's disease without dementia (PD), and Alzheimer's disease (AD) using three-dimensional stereotactic surface projection (3D-SSP) analysis., Purpose: We attempt to clarify the difference of reduction pattern on SPECT among patients having DLB, PDD, PD, AD., Patients and Methods: Six patients with DLB, 7 patients with PDD who were matched with the DLB patients for age, unified Parkinson's disease rating scale-III (UPDRS-III) score, and degree of cognitive function disorders, 21 patients with PD who were matched with the DLB patients for age, UPDRS-III score, 12 patients with AD who were matched with the DLB patients for age and degree of cognitive function disorders, and 12 control subjects. All patients were examined by N-isopropyl-p[123I] iodoamphetamine single photon emission computed tomography (123I-IMP SPECT), and obtained images were analyzed with 3D-SSP using an image-analysis software, iSSP ver. 3.5., Results: Although DLB and PDD showed similar cerebral perfusion reduction pattern at the lateral parietal association and lateral temporal association and precuneus on SPECT by the pixel-by-pixel comparison, greater perfusion reduction was observed in DLB than in PDD. Cerebral perfusion was decreased at the occipital lobe of the DLB patients compared with the AD patients., Conclusions: The regional pattern of blood flow reduction in the brain was found to be different among DLB, PD, and AD. Greater blood flow reduction was observed in DLB, although DLB and PDD showed similar reduction pattern. These regional differences were considered to suggest different and disease-specific combinations of underlying pathological and neurochemical processes.

Objective: To determine the efficacy and safety of unilateral deep brain stimulation on the posterior subthalamic white matter, including the zona incerta (ZI) and the prelemniscal radiation (PRL), for tremor-dominant parkinsonian patients and to determine the exact location of electrodes that were most effective., Methods: Eight parkinsonian patients with severe resting tremor underwent unilateral stimulation of the ZI/PRL by use of stereotactic guidance. Electrophysiological targeting was obtained by macrostimulation and by somatosensory evoked potentials recorded directly through a quadripolar deep brain stimulation lead. Postoperative computed tomographic scans and magnetic resonance images were performed to confirm anatomic location of the electrode. Parkinsonian motor disabilities were evaluated by use of the Unified Parkinson's Disease Rating Scale in the medication-off state before surgery and every 6 months after electrode implantations., Results: The mean location of the clinically effective contacts was in the posterior subthalamic white matter, including the ZI and the PRL (mean, 5.6 +/- 1.2 mm posterior to the midcommissural point, 3.2 +/- 1.1 mm inferior to the anterior commissure-posterior commissure line, and 10.5 +/- 1.2 mm lateral to the midline). At 24 months after operation, ZI/PRL stimulation resulted in significant improvement in mean Unified Parkinson's Disease Rating Scale motor score by 44.3%, contralateral tremor by 78.3%, contralateral rigidity by 92.7%, and contralateral akinesia by 65.7% above the "off-stimulation" scores. Handwriting, posture, and gait were also improved. There were no or only mild adverse events., Conclusion: Unilateral ZI/PRL stimulation is a reliable and long-term therapeutic modality and can be considered another surgical target for the treatment of tremor-dominant Parkinson's disease.

We previously reported that exogenously administered isatin, an endogenous monoamine oxidase (MAO) inhibitor, significantly increased acetylcholine (ACh) and dopamine (DA) levels in the rat striatum. Selegiline [(-)-deprenil] was developed as a MAO-B inhibitor more than 30 years ago and widely used in the treatment of Parkinson's disease. Effects of isatin or selegiline were investigated in Japanese encephalitis virus (JEV)-induced post-encephalitic parkinsonism rats by a pole test for detecting motor activity and by the determination of biogenic amine levels. Motor activity of JEV-induced rats receiving isatin (100 mg/kg per day for 1 week, i.p.) or selegiline (0.2 mg/kg per day for 1 week, i.p.) was significantly improved compared with that of untreated JEV-infected rats. Both isatin and selegiline prevented the decrease in striatal DA levels in JEV-rats. The increased turnover of DA (DOPAC/DA) induced by JEV was significantly inhibited by isatin, but not by selegiline. These results suggested that exogenously administered isatin and selegiline can improve JEV-induced parkinsonism by increasing DA concentrations in the striatum.

Using the dual task paradigm, previous studies have suggested that working memory (WM) deficit is due to depleted attention resources in patients with Parkinson's disease (PD). The aim of this study is to establish whether the WM problems in PD are due to reduced attentional set-shifting resources rather than depletion of attention resources. The task design attempts to eliminate confounding of the deficits in dealing with novel material, a problem documented in PD, by concentrating on WM tasks of mental calculation that are familiar to subjects in daily living. We also administered attention tasks, the Trail Making Test (TMT) that relies primarily on attentional set-shifting and the Kana (Japanese syllabogram) Pick-out Test instead primarily depending on depleted attention resources for allocation. A total of 24 patients with PD and 24 normal controls participated in this study. The PD group showed deficits in mental calculation span and in attentional set-shifting in the TMT-b.Considering the common deficits in alternating processing of mental calculation and TMT-b in PD, the results suggested that the central executive dysfunction in PD during mental calculations was due to reduced attentional set-shifting resources for rapidly alternating operations, rather than the depletion of attentional resources.

The purpose of this study was to investigate the age-related working memory(WM) decline in patients with Parkinson's disease(PD) using Baddeley's WM model. This model consists of the central executive (CE) and two slave systems, the phonological loop (PL) for the storage of verbal materials, and the visuospatial sketchpad(VSSP) for the storage of visuospatial information. The participants of this study were 22 PD, 11 old (age of 68-78, mean age, 70.5) and age of onset, duration of illness, medication time, and Yahr stage, global cognitive status-matched 11 young(age of 39-58, mean age, 51.5) PD, age- and educational years, global cognitive status-matched 22 normal control (NC), 11 old(age of 65-78, mean age, 70.4) and 11 young(age of 45-57, mean age, 52.4). Mental calculation span of digit sequences, digit forward and backward span, visual memory span were carried out. Age related decline of WM was found in both groups, but processing related differences were revealed between the two groups. NC group showed significant decline with aging in digit backward span. In contrast, in mental calculation span, PD groups showed significant deficit revealed in young PD group and declined significantly with aging and significant decline was not found in digit backward span. In term of the processing and difficulty of WM tasks, digit backward span that needs maintenance of digit sequences and re-ordering, was more difficult than mental calculation that needs maintenance of digit sequences, summation of the digit and updating of the results. There were not significant differences between four groups in digit forward span, visual memory span. The results indicated that the WM span in normal aging declined as task difficulty increased. Their performance decline may be caused by the CE dysfunction. On the other hand, PD showed a characteristic CE deficit observed in mental calculation even in young age and decline with aging. Such decline may be caused by peculiar processing related dysfunction of CE that assumes to be essential deficit of PD.

Diagnostic criteria for Parkinson's disease is used in all clinical studies concerning this disease. For supplying meaningful data to the evidence-based medicine, the diagnostic criteria must be clearly defined in such studies. In the setting and usage of diagnostic criteria, it is indispensable to clarify the aim and the population for which the criteria is used. Then, as for the contents of the criteria, 1) additional criteria, 2) exclusion criteria, and 3) levels of confidence must be considered. For the future re-evaluation, diagnostic criteria must be logic. Final references are also necessary for judging the accuracy of the criteria.

Isatin, an endogenous monoamine oxidase (MAO) inhibitor, has been found in mammalian tissues. We previously reported that exogenously administered isatin significantly increased acetylcholine (ACh) and dopamine (DA) levels in the rat striatum. In order to elucidate the relationship between isatin and Parkinson's disease, we measured urinary isatin excretions in patients with Parkinson's disease using a newly developed HPLC-UV method. The recovery of this assay was approximately 102.3% at a range from 2 to 50 nmol/ml. The Coefficient of Variance (CV) for the determination at this range was approximately 2.5% for intra-assay and 6.2% for inter-assay, respectively. There was no significant difference in urinary isatin excretion between data from men and women in healthy control. The value in young age group (19-35 years old) was not significantly different compared with that of the older age group (54-84 years old). Urinary isatin levels in patients with Parkinson's disease tended to increase in accordance to the Hoehn and Yahr criteria. This is the first study in which a significant increase in urinary isatin excretion was observed at Stage III, IV and V in patients with Parkinson's disease. Urinary isatin concentrations in drug-treated patients with Parkinson's disease (at Stage I and II) tended to decrease compared with those of patients without medication. These results demonstrated that urinary isatin excretion may serve as an endogenous diagnostic marker for the clinical severity of Parkinson's disease.

The clinical, pathophysiological and therapeutic approaches to the representative involuntary movements encountered in the aged are described. The prevalence rates of Parkinson disease and essential tremor are very high, and their diagnoses and treatments are quite important. Recent advances in treating Parkinson disease with anti-parkinsonian medications and essential tremor with beta-adrenergic blockers were presented. Blepharospasms, though uncommon, but occasionally seen in the aged persons, are disabled conditions. The botulinus toxin injections to the orbicularis oculi muscles proved to show dramatic therapeutic effects, greatly contributing to these patients' ADL. The importance of neuroscience in the coming 21st century is also stressed.

In Fischer rats infected with Japanese encephalitis virus (JEV) at 13 days after birth and sacrificed 12 weeks later, the major pathological changes resembled those found in Parkinson's disease. Specifically there was neuronal loss with gliosis which was confined mainly to the zona compacta of the substantia nigra, with a notable absence of lesions in the cerebral cortex and cerebellum. Changes were bilateral being most severe in the central part of the zona compacta. Immunohistochemical studies with anti-tyrosine hydroxylase (TH) demonstrated that the number of TH-positive neurons was significantly decreased in the substantia nigra compared to controls, while comparable numbers of TH-positive neurons were found in the basal ganglia in both JEV-treated rats and age-matched controls. JEV-infected rats showed marked bradykinesia, with significant behavioral improvement being observed following administration of L-DOPA. Immunohistochemical studies failed to detect JEV antigens in any region of the rat brain and the JEV genome was undetectable in the substantia nigra and the cerebral cortex using the reverse transcription-polymerase chain reaction (RT-PCR). The findings suggest that JEV infection of rats under the conditions described may serve as a model of virus induced Parkinson's Disease.

A 10-year nationwide multicenter prospective study on the long-term efficacy of bromocriptine for Parkinson's disease is reported. Six patients remained on bromocriptine monotherapy for 10 years, while 22 patients achieved good disease control with bromocriptine plus levodopa (added during the course of the study). In the 6 patients on bromocriptine alone, the disease remained in Hoehn and Yahr stage I or II for 10 years. In the other 22 patients on bromocriptine plus levodopa therapy, disease progression was very slow for 7-8 years. None of the 6 patients remaining on bromocriptine monotherapy experienced adverse reactions like the wearing-off phenomenon, dyskinesia, or the on-off phenomenon. Among the 22 patients who started levodopa therapy during the course of the study, these adverse reactions to levodopa were infrequent (10, 3, and 3 patients, respectively). Thus, early introduction and long continuation of bromocriptine therapy with restricted concomitant use of levodopa may have led to very slow disease progression and the suppression of adverse reactions. Although the patients who could be maintained long-term on bromocriptine monotherapy might represent a population who have very slowly progressive disease, their adequate disease control and the low incidence of adverse reactions in the patients who later started concomitant levodopa suggest that the unwanted effects of levodopa may be reduced by early and sustained treatment with bromocriptine. Introduction of bromocriptine monotherapy at an early stage of Parkinson's disease or with restricted use of additional levodopa therapy to bromocriptine when necessary may be a useful strategy for achieving adequate and sustained disease control.

A 9-year nationwide study of bromocriptine monotherapy and combination therapy with bromocriptine and levodopa in Parkinson's disease is reported. Eleven patients were on bromocriptine monotherapy, 35 patients were on combined treatment of bromocriptine and levodopa for a certain time during a 9-year period. Maintenance doses of bromocriptine at the end of the 9th year in the two groups were 11.1 mg/day in the monotherapy and 12.7 mg/day in the combination therapy group with levodopa. Changes in Hoehn and Yahr's grading between the time of trial start and the end of 108 months' treatment revealed that 5 of 11 cases in the monotherapy group remained in the same stages, the other 2 cases improved in condition from stage II to I, and another 4 deteriorated compared with pretreatment grade. On the other hand, 20 of 35 cases in the combination-therapy group reached more advanced stages, 3 patients moving to stage V. Four of them, however, improved, and 11 did not change at the end of 9 years of treatment. Although it is difficult to prove the neuroprotective effect of a dopamine receptor agonist, our long-term nation-wide collaborative studies will help us to answer the question of how bromocriptine works in pharmacokinetic aspects.

We studied regional cerebral blood flow (rCBF) in 8 patients with non-demented Parkinson's disease (PD). 1 patient with progressive supranuclear palsy (PSP), 1 patient with multiple system atrophy (MSA), and 7 normal control subjects using single photon emission computed tomography (SPECT) with the IMP-ARG method. Regions of interest were studied in the cerebral cortex (upper frontal, lower frontal, temporal, occipital, parietal), thalamus, basal ganglia, and cerebellum. In patients with PD, rCBF was normal in 4/8, and decreased in occipital lobe in 4/8. In patient with PSP, rCBF was decreased in the upper and lower frontal lobes, and in the cerebellum. In patient with MSA, rCBF was diminished in the cerebellum. The results of our study were almost compatible with the conventional rCBF study by positron emission tomography (PET), however, the decrease of rCBF in occipital lobe had rarely been reported, suggesting that might be related to visuospatial dysfunction in Parkinson's disease.

The prevalence of Parkinson's disease (PD) was investigated in Hokkaido, the northernmost island of Japan. A pilot case-finding study was carried out to estimate the prevalence in the entire island of Hokkaido (population = 5,643,647) initially, then we surveyed the prevalence at one of the smaller cities, Iwamizawa City (population = 80,417). We ascertained 5,342 cases with PD in Hokkaido and 77 cases in Iwamizawa City, estimating the crude prevalence of 94.7/100,000 in Hokkaido (June 30, 1993) and 95.8/100,000 in Iwamizawa City (April 1, 1994), respectively. We calculated that the crude prevalence rate of PD in Japan in currently close to 100/100,000, but the age-adjusted prevalence is still low, compared with those in Europe and North America.

An 8-year nationwide study of bromocriptine monotherapy and combination therapy with bromocriptine and levodopa in Parkinson's disease is reported. Fifteen patients were on bromocriptine monotherapy, and 44 patients on bromocriptine combined with levodopa for a certain time during an 8-year period. By judging from Hoehn and Yahr's grading, 4 of the 15 patients in the monotherapy group were in a better condition than before treatment, while 7 cases remained in the same grading, and only 4 showed deterioration. On the other hand, 26 of 44 patients on combination therapy showed more advanced grading at the end of 8 years compared to the stage at the onset of the trial. Maintenance doses of bromocriptine in the two groups were 12-13 mg per day, and levodopa doses were kept at a relatively low level (310-370 mg per day) during this study period. Whether dopamine receptor agonists have neuroprotective effect or not is extremely difficult to prove in human subjects, but this type of long-term follow-up study might give some clues as to these important questions.

We studied voluntary control of saccadic eye movement in 32 parkinsonian patients using the antisaccade task (the subjects were instructed not to look at the target but to look in the opposite direction). Mean latencies and error rates in the antisaccade task were significantly increased in advanced parkinsonian patients. The latencies of the antisaccades correlated with the severity of bradykinesia as well as the results of the Wisconsin Card Sorting Test. Patients taking anticholinergics showed significantly higher error rates. These results suggest that disturbance in the initiation of voluntary saccades in advanced patients may be associated with frontal lobe dysfunction, while anticholinergics may affect the inhibitory control of reflexive saccades.

A 7-year nationwide study of bromocriptine monotherapy and combination therapy with bromocriptine and levodopa in Parkinson's disease is reported. Of 22 patients who had been on bromocriptine monotherapy for 7 years (group B), 16 remained improved or remained in the same stages of Hoehn and Yahr, and no wearing-off phenomenon or dyskinesia was observed. In another 56 patients who were started on bromocriptine alone, but in whom combination therapy with levodopa was instituted at some time in the 7 years (group BL), disease progressed faster than in group B. A wearing-off phenomenon and dyskinesia occurred in 34% and 5.4% of the patients, respectively. These manifestations appeared only after initiation of levodopa. The favorable course of group B suggests possible neuroprotective effects of bromocriptine or may be due to the inevitable selection of patients who had a favorable course originally.

A 68-year-old woman with parkinsonism showed cortical myoclonus and seizures under antiparkinsonian medication. Myoclonus was induced and enhanced by L-dopa, developing into generalized seizures. EEG was abnormal and somatosensory-evoked potentials (SEPs) showed giant SEPs, transcortical reflex (C reflex) and jerk locked potentials. Myoclonus and seizures disappeared after discontinuation of L-dopa and the introduction of valproate sodium (VPA). We described the occurrence of L-dopa-induced myoclonus and seizures in a case of parkinsonism with its SEPs findings.

The width of substantia nigra (SN) in 59 cases with idiopathic Parkinson's disease as well as 21 normal controls was analyzed by T2 weighted image (T2WI) of 1.5 Tesla high-field magnetic resonance image (MRI). All patients and controls underwent MRI with the spin-echo sequences used TR/TE: 3000/30 (short TE), and TR/TE:3000/80 (long TE), in 5-mm-thick volumes. The width between the red nucleus and the cerebral peduncle showing low signal intensity areas was measured as that of SN and its ratio to the distance from the aqueduct to the midline of the cerebral peduncle was also measured. The calculated values of the width of SN and its ratio were analyzed by Mann-Whitney test. The significant reduction in the width of SN and its ratio in Parkinson's disease were disclosed as below; the mean calculated values of the width of SN were 2.95 +/- 0.51 mm in controls, 2.68 +/- 0.99 mm in Parkinson's diseases on long TE images (P less than 0.01), and the mean ratio of the width of SN were 13.58 +/- 4.21% in controls, 10.52 +/- 3.07% in Parkinson's diseases on long TE images (P = 0.0002). The narrowing of SN in Parkinson's disease was more prominent in men, and advanced cases with Yahr stage III and IV. Considering that the pars reticulata, which is normally containing iron, shows low signal intensity on long TE images, the width of pars compacta could be measured more precisely on this sequences. The evaluation of the ratio of SN in midbrain on long TE images seemed to be more sensitive than the calculated values in detecting the narrowing of SN and pars compacta in Parkinson's disease.

We report on the clinical efficacy of a slow-release formulation of bromocriptine studied in a multi-center, double-blind trial using standard bromocriptine as the control. We randomly allocated enrolled patients (N = 243) to either the slow-release or normal bromocriptine group. Sixty of them were de novo patients. The maintenance dose of slow-release bromocriptine was 14.2 +/- 0.7 mg/d and that of standard bromocriptine 13.5 +/- 0.7 mg/d (mean +/- SE). The slow-release formulation was taken twice and the standard three times a day. Forty-one percent of the patients treated with the slow-release bromocriptine and 32% of the patients treated with the standard bromocriptine showed moderate or marked improvement in the global improvement rating. There were no serious side effects, and the frequency of vomiting and epigastric discomfort was lower in the patients treated with the slow-release bromocriptine. Clinical efficacies for tremor, rigidity, akinesia, and gait disturbance were comparable between the two drugs tested. The slow-release bromocriptine seems to be a valuable drug for the treatment of Parkinson's disease with less severe side effects than regular bromocriptine.

Changes in coordinated eye and hand movements associated with the progress of bradykinesia were studied in 31 parkinsonian patients and 8 age-matched healthy subjects. Among the parameters expressing the changes in motor behaviour, the interval between the onset of eye and hand movements was most sensitive. This parameter reflected the difference in the progress of the symptom in the two motor systems. An increase in the reaction time of the hand response appeared in patients of grade II bradykinesia; this was observed for eye movements only in patients with grade III (severe) bradykinesia. While the changes in ocular reaction time remained within the physiological range, a lengthening of the reaction time, a reduction in peak velocity, a decrease in the open-loop gain, a prolongation of movement duration, and a slow build-up in EMG activity, appeared from an early stage in hand movement. These signs of motor disturbance may appear eventually in every motor system at an advanced stage, but their development is not synchronous in different motor systems. An analysis of the responses recorded simultaneously from the two motor systems examined made it possible to evaluate the changes in the sensorimotor processes with different grades of bradykinesia. A comparison between reaction times for eye and hand movements may be useful for assessing the degree of bradykinesia in parkinsonian patients.