Gait freezing and speech disturbance in Parkinson's disease.

Gait freezing and speech disturbance are disabling axial features of Parkinson's disease (PD). However, the pathogenesis of these features remains unclear. We investigated the relation between changes in gait freezing and speech disturbance using visual and auditory cues in PD. 18 PD patients, comprising of 9 patients with freezing (PDGF) and 9 without gait freezing were studied. Patients performed a 7-m back-and-forth walk in a baseline state and with visual and auditory cues. Gait velocity, stride length and cadence were evaluated using a three-dimensional gait analysis system. For speech evaluation, patients read ten sentences in a baseline state and with visual and auditory cues. The time delay of speech initiation, speech rate and the number of repetitions per sentence were quantified. In PDGF patients, the increase in gait velocity positively correlated with the decrease in the time delay of the speech initiation. Also, the increase in the gait velocity and cadence positively correlated with the decrease in the number of repetitions per sentence. The increase in the stride length positively correlated with the increase in speech rate. Lastly, the increase in stride length positively correlated with the decrease in the number of repetitions per sentence. These findings suggest that there is a common pathomechanism of gait freezing and speech disturbance in PD.

Visual hallucinations and cognitive impairment in Parkinson's disease.

BACKGROUND: Visual hallucination (VH) is a common psychotic symptom in patients with Parkinson's disease (PD) and may be a significant predictor of cognitive impairment (CI) in such patients. OBJECTIVE: This study aimed to investigate the pattern of glucose metabolism of VH and the relationship between VH and CI in PD. METHODS: We studied 28 PD patients, including 15 with VH (PD-VH) and 13 without VH (PD-NVH). Of the 15 PD-VH patients, 8 patients had cognitive impairment (PD-VHCI) whereas 7 did not (PD-VHNCI). All patients underwent [18F] fluorodeoxyglucose positron emission tomography ([18F] FDG PET) followed by statistical parametric mapping (SPM) analyses. RESULTS: Compared to the patients with PDNVH, PD-VHNCI patients showed glucose hypometabolism in the inferior and middle temporal cortices, fusiform gyri, and frontal areas, suggesting the involvement of the ventral visual pathway. Compared to the patients with PDNVH, PD-VHCI patients showed glucose hypometabolism in the temporoparietal association cortices with scattered frontal areas. CONCLUSION: Dysfunction of ventral visual pathway involving the temporal lobe may play a key role in VH development in PD patients. The evolving distribution from the ventral visual pathway to more extensive posterior cortices in PD-VHCI patients suggests that VH may be a prodromal symptom occurring prior to CI in PD patients.

Levosulpiride-induced movement disorders.

Levosulpiride is a substituted benzamide that is widely used for the management of dyspepsia and emesis. However, little is known about levosulpiride-induced movement disorders (LIM). The aim of this study was to investigate the clinical characteristics of patients with LIM. Among 132 consecutive patients who were diagnosed with drug-induced movement disorders between January 2002 and March 2008, 91 patients with LIM were identified and their medical records reviewed. Seventy-eight (85.7%) patients were aged more than 60 years. The most common LIM was parkinsonism (LIP) (n = 85, 93.4%), followed by tardive dyskinesia (n = 9, 9.9%) and isolated tremor (n = 3, 3.3%). Twenty-one (24.7%) of the 85 patients with LIP were rated as Hoehn and Yahr stage III-V. The oro-lingual area was the only body part that was involved by tardive dyskinesia. LIM persisted after withdrawal of levosulpiride in 48.1% of patients with LIP, 66.7% with dyskinesia, and none with isolated tremor. None of clinical and MRI features predicted the reversibility of LIP. Levosulpiride frequently causes drug-induced movement disorders, presenting mainly with LIP followed by lower face dyskinesia. The symptoms are often severe, and irreversible even after the withdrawal of levosulpiride. Physicians should be cautious in using levosulpiride, especially in elderly patients.

Functional brain imaging in pure akinesia with gait freezing: [18F] FDG PET and [18F] FP-CIT PET analyses.

Pure akinesia with gait freezing (PAGF) has characteristic features, including freezing of gait and prominent speech disturbance without rigidity or tremor. The purpose of this study was to investigate changes in brain glucose metabolism and presynaptic dopaminergic function in PAGF. By using [(18)F] fluorodeoxyglucose (FDG) PET, 11 patients with PAGF were compared with 14 patients with probable progressive supranuclear palsy (PSP), 13 patients with Parkinson's disease (PD), and 11 normal controls. [(18)F] N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane (FP-CIT) PET was performed in 11 patients with PAGF and with 10 normal controls. The PAGF patients showed decreased glucose metabolism in the midbrain when compared with normal controls. PSP patients showed a similar topographic distribution of glucose hypometabolism with additional areas, including the frontal cortex, when compared with normal controls. The FP-CIT PET findings in patients with PAGF revealed severely decreased uptake bilaterally in the basal ganglia. These findings suggest that both PAGF and PSP may be part of the same pathophysiologic spectrum of disease. However, the reason why PAGF manifests clinically in a different manner needs to be further elucidated.

Factors predicting response to dopaminergic treatment for resting tremor of Parkinson's disease.

We aimed to evaluate the clinical factors predicting response to dopaminergic treatment for resting tremor in patients with Parkinson's disease (PD). Eighty-five PD patients with prominent resting tremor, defined as tremors of score greater than 3 in at least one limb on the Unified Parkinson's Disease Rating Scale (UPDRS), were divided into those responsive or nonresponsive to dopaminergic treatment. Responsiveness was defined as a reduction of at least two points for more than 3 months in the UPDRS tremor score. Of the 85 patients, 36 (42.4%) were responsive and 49 (57.6%) were nonresponsive to dopaminergic treatment. Initial UPDRS III score (P = 0.015) and Hoehn and Yahr stage (P = 0.010) were each significantly higher in the RG than in the NRG. UPDRS subscores for rigidity (P = 0.012), bradykinesia (P = 0.021) and postural impairment (P = 0.018) also correlated with responsiveness to dopaminergic treatment. Resting tremor in PD patients was more responsive to dopaminergic treatment when accompanied by moderate degrees of bradykinesia and rigidity than in patients without other prominent parkinsonian features.

Effect of thalamotomy on focal hand dystonia in a family with DYT1 mutation.

We report the clinical and molecular features of a family with focal hand dystonia caused by DYT1 mutation. Four members of a family who underwent thalamotomy showed a marked and sustained therapeutic benefit that lasted for up to 12 years without recurrence of dystonia or any significant surgical complication. The hand dystonia caused by DYT1 mutation may be successfully managed by thalamotomy.

Differential patterns of dopamine transporter loss in the basal ganglia of progressive supranuclear palsy and Parkinson's disease: analysis with [(123)I]IPT single photon emission computed tomography.

We evaluated the patterns of dopamine transporter loss in the striatum of ten controls, twenty patients with Parkinson's disease (PD), and nine with progressive supranuclear palsy (PSP) using (123)I-IPT single photon emission tomography (SPECT). Four ROIs in the striatum correspond to the head of caudate nucleus (ROI 1), a transitional region between head of caudate and putamen (ROI 2), anterior putamen (ROI 3), and posterior putamen (ROI 4). A striatal ratio of specific to nondisplaceable uptake (V3'') was calculated normalizing the activity of the ROIs to that of occipital cortex. V3'' values were significantly reduced in all ROIs of PD and PSP patients, compared with controls (p=0.001). V3'' value in ROI 2 was significantly lower in PSP group, compared with PD group (p=0.02). The percent reductions of striatal uptake in ROI 1, ROI 2, ROI 3 and ROI 4 were 56%, 53%, 64% and 78% in PD patients, whereas 75%, 72%, 75% and 77% in PSP patients, respectively. The reduction patterns of uptake were significantly different between PD and PSP groups (p=0.001). In PD patients, the percent reductions of (123)I-IPT uptake were significantly greater in ROI 3 and 4 compared with ROI 1 or 2, whereas those were similar in all ROIs of PSP patients. In addition, PD patients showed a significantly higher posterior putamen/caudate ratio of reduced (123)I-IPT uptake than the anterior putamen/caudate ratio (p=0.005). Our results implicate that (123)I-IPT SPECT is a relatively simple and reliable technique that may be useful in differentiating PD from PSP.

Hemichorea after stroke: clinical-radiological correlation.

Post-stroke hemichorea is an uncommon involuntary hyperkinetic disorder involving unilateral body parts. The incidence and precise lesion location of post-stroke hemichorea remain unclear. The authors describe 27 consecutive patients with hemichorea after stroke. The incidence of post-stroke hemichorea was 0.54 % (27 out of 5,009 patients). The lesions were located in the caudate and putamen (n = 6), cortex (n = 6), thalamus and subthalamic area (n = 4), subthalamus (n = 4), putamen (n = 3), caudate (n = 2), and the globus pallidus (n = 2). Over the mean follow-up period of 22 months, the hemichorea disappeared in 56% of the patients, while it persisted in others. The rate of disappearance of hemichorea was significantly higher in patients with cortical strokes than in those with subthalamic lesions (P < 0.05). We conclude that hemichorea is a rare manifestation of stroke and most often produced by lenticular lesions followed by subthalamic and cortical lesions. The functional prognosis is better in patients with cortical lesions than those with subthalamic strokes.

Ropinirole as an adjunct to levodopa in the treatment of Parkinson's disease: a 16-week bromocriptine controlled study.

BACKGROUND: and objectives Ropinirole is a non-ergoline, selective dopamine D(2) agonist. The aim of this study was to evaluate the efficacy and safety of ropinirole as an adjunct to levodopa in the treatment of Parkinson's disease (PD) complicated by motor fluctuations. METHODS: A total of 76 patients with PD (Hoehn and Yahr stage II to IV) were included in this trial. Each patient was randomly allocated to receive either ropinirole (n = 37) or bromocriptine (n = 39) as an adjunct to levodopa over a 16-week period. Ropinirole and bromocriptine were titrated for optimal efficacy and tolerability. This optimal dose was then maintained for the rest of the study. Response rate was defined as the percentage of patients who achieved at least a 20 % reduction in levodopa dose. Clinical status was also assessed using the Unified Parkinson's Disease Rating Scale (UPDRS), Clinical Global Impression (CGI), and reduction in time spent 'off'. RESULTS: Ropinirole produced a significantly greater response rate than bromocriptine (odds ratio 2.995, 95 % C. I. (1.157, 7.751) p < 0.05). There was also a statistically significant difference between the groups in the proportion of patients who were 'improved' on the CGI improvement scale (91.9 % for ropinirole, 74.3 % for bromocriptine, p = 0.046). Other measures, including at least a 20 % improvement in the UPDRS motor score (70 % for ropinirole and 63.3 % for bromocriptine), and a 20 % reduction in 'off' duration (81 % for ropinirole and 52.4 % for bromocriptine) showed a trend in favour of ropinirole. There was no significant difference between the two groups in the overall incidence of adverse effects (ropinirole, 59.5 %; bromocriptine, 59 %). In each group, the most common side-effects were dizziness, dyskinesia and nausea/vomiting. No patients were withdrawn from the study because of side-effects. CONCLUSION: Ropinirole was found to be safe and well-tolerated. Ropinirole as an adjunct to levodopa in the treatment of PD with motor fluctuation was associated with more significant reduction of levodopa dose and, on one form of analysis, with significantly greater improvement in CGI ratings than bromocriptine. On the other efficacy measures the two drugs were comparable.

Lateralized effects of unilateral thalamotomy and thalamic stimulation in patients with essential tremor.

BACKGROUND AND PURPOSE: Stereotactic thalamotomy has been an effective surgical procedure in the treatment of medically refractory essential tremor (ET), however, little is known about the bilateral effects of unilateral ventralis intermedius (Vim) thalamotomy and Vim deep brain stimulation (DBS). We studied the lateralized effects of unilateral Vim thalamotomy and Vim DBS in ET patients. METHODS: Vim thalamotomy was performed in 6 patients and Vim DBS in 6. Patients were evaluated preoperatively and at 3 and 6 months postoperatively using the Clinical Rating Scale for Tremor (CRST). RESULTS: The contralateral Part A (tremor localization/severity rating) and Part B (specific motor tasks/function rating) subscores, and axial subscores of CRST significantly improved after unilateral Vim thalamotomy or Vim DBS. On the side ipsilateral to surgery, ET patients demonstrated no significant improvements in the Part A and Part B subscores of CRST. The Part C (functional disabilities resulting from tremor) subscores and total scores of CRST were significantly improved after surgery. CONCLUSIONS: Vim thalamotomy and DBS may be equally effective for the management of contralateral and axial tremor in ET patients, but both interventions may not improve tremor on the side ipsilateral to surgery.

Nigrostriatal dysfunction in patients with amyotrophic lateral sclerosis and parkinsonism.

The pathomechanism of amyotrophic lateral sclerosis (ALS) with parkinsonism (ALS-P) has not been clarified. We report two patients with ALS-P who showed dysfunction of the nigrostriatal system. The first patient showed tremor dominant, asymmetric parkinsonism which was more severe on the right side, while the second patient exhibited predominant freezing of gait. Both patients showed reduced uptake of [¹8F] N-(3-fluoropropyl)-2ß-carbon ethoxy-3ß-(4-iodophenyl) nortropane (¹8F-FP-CIT) in the posterior parts of bilateral putamina on positron emission tomography (PET). Based on our PET findings, we suggest that presynaptic nigrostriatal dysfunction may be involved in the pathomechanism of parkinsonism combined with ALS.

Use of complementary and alternative medicine by Korean patients with Parkinson's disease.

OBJECTIVES: Many patients with Parkinson's disease (PD) often utilize complementary and alternative medicine (CAM). We aimed to survey the prevalence, spectrum of use, and factors related to utilization of CAM in patients with PD in Korea. PATIENTS AND METHODS: Between 15 December 2005 and 30 April 2006, we studied 123 patients with PD who volunteered to be interviewed using semi-structured questionnaires. RESULTS: Ninety-four (76%) patients had used CAM. The mean cost of CAM paid by patients (out-of-pocket costs) was 102.3 US Dollars (USD) per month, while medical costs of treatment for PD paid by patients (out-of-pocket costs) averaged 72.8 USD per month. Patients using CAM sought to improve motor symptoms (57.6%), fatigue (19.6%), pain (4.3%), constipation (5.4%) or specified no single reason (13.0%). The spectrum of CAM use included oriental medicines (76.6%), traditional food (44.7%), non-prescribed drugs (31.9%), traditional therapies (7.4%), massage (7.4%) and behavioral therapy (7.4%). Factors related to current use of CAM were disease duration, degree of education, and daily levodopa equivalent dose. In a logistic regression analysis, the duration of PD was a significant factor for CAM use. CONCLUSIONS: These results suggest that a high proportion of Korean PD patients employed CAM, associated with high costs and serious side effects in some patients.

Fibrillin-1 gene analysis of Korean patients with spontaneous CSF hypovolemia.

BACKGROUND: Mutations in different domains of the Fibrillin-1 (FBN1) gene may be responsible for the variable phenotypic expression of Marfan's syndrome that may present with CSF hypovolemia. OBJECTIVES: To evaluate the association between mutations in the Fibrillin-1 (FBN1) gene and spontaneous CSF hypovolemia (SCH) in a Korean population. METHODS: We studied 10 consecutive patients with SCH without clinical characteristics of Marfan's syndrome. The genetic analysis was performed. RESULTS: Direct sequencing analysis of the FBN1 gene identified 15 genetic variations, of which 5 coding (3 synonymous, 2 nonsynonymous) and 8 intronic variations were listed in the single nucleotide polymorphism database (dbSNP). The other 2 variations, c.2728 - 12T > C in intron 21 and c.4582 - 19A > G in intron 35, were also observed in normal controls with estimated frequencies of 0.06 and 0.15, respectively. CONCLUSIONS: We could not identify any FBN1 variations possibly associated with SCH in our study population.

Comparison of brain MRI and 18F-FDG PET in the differential diagnosis of multiple system atrophy from Parkinson's disease.

To investigate the diagnostic value of brain magnetic resonance image (MRI) and (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) in the differentiation of multiple system atrophy (MSA) from Parkinson's disease (PD). Thirty-five patients with MSA (23 MSA-P and 12 MSA-C) and 17 patients with PD were included in this study. Overall correct diagnosis rates between clinical and imaging diagnosis among MSA-P, MSA-C, and PD patients were 80% for visual MRI analysis, 88.5% for visual (18)F-FDG PET analysis, and 84.3% for SPM-supported analysis of (18)F-FDG PET. The sensitivity of brain MRI, and visual and SPM analysis of (18)F-FDG PET in differentiating MSA from PD was 72.7%, 90.9%, and 95.5%, respectively, the specificity was 100% for each imaging analysis, the positive predictive value was 100% for each imaging analysis, and the negative predictive value was 60%, 81.8%, and 90%, respectively. Our results suggest that brain MRI and (18)F-FDG PET are diagnostically useful in differentiating MSA (MSA-P and MSA-C) from PD, and indicate that (18)F-FDG PET has a tendency toward higher sensitivity compared to brain MRI, but a larger longitudinal study including pathological data will be required to confirm our findings.

Efficacy and safety of simultaneous bilateral pallidotomy in advanced Parkinson's disease.

BACKGROUND: Although unilateral pallidotomy is generally considered a safe and effective neurosurgical treatment for advanced Parkinson's disease (PD), controversies concerning efficacy and adverse effects of bilateral posteroventral pallidotomy (PVP) exist and need to be resolved. METHODS: We studied 8 patients with advanced PD who underwent simultaneous bilateral PVP. The patients were assessed preoperatively, immediately after surgery, and 6 and 12 months later. RESULTS: Dyskinesia was almost entirely abolished immediately after surgery, as well as being significantly lower 1 year later (p < 0.05). The 'off' medication score of the Unified Parkinson's Disease Rating Scale motor part (UPDRS III) was significantly improved after surgery (p < 0.05) but increased gradually after 6 months. The off medication score of activities of daily living tended to improve immediately after surgery, but it returned to preoperative levels at 12 months. There were no major complications of surgery. CONCLUSIONS: Simultaneous bilateral PVP may be a safe and highly effective method of reducing levodopa-induced dyskinesia. Our results suggest that simultaneous bilateral PVP may be a reasonable therapeutic option for advanced PD with severe levodopa-induced dyskinesia.