Cerebellar degeneration associated with Sjögren's syndrome.

BACKGROUND: Neurologic manifestations of primary Sjögren's syndrome (PSS) have been reported to vary from sensory polyneuropathy to encephalopathy or psychiatric problems. However, marked cerebellar degeneration associated with PSS has rarely been reported. CASE REPORT: We describe a patient with Sjögren's syndrome who exhibited rapidly progressive cerebellar ataxia, nystagmus, cognitive decline, and psychiatric problems. Brain magnetic resonance imaging revealed marked atrophy of the cerebellum, and (18)F-fluorodeoxyglucose positron-emission tomography demonstrated glucose hypometabolism of the cerebellum. CONCLUSIONS: Our PSS patient exhibited a progressive course of cerebellar syndrome, as evidenced by cerebellar atrophy on serial brain images.

Overnight switch from ropinirole to transdermal rotigotine patch in patients with Parkinson disease.

BACKGROUND: A recent trial involving predominantly Caucasian subjects with Parkinson Disease (PD) showed switching overnight from an oral dopaminergic agonist to the rotigotine patch was well tolerated without loss of efficacy. However, no such data have been generated for Korean patients. METHODS: This open-label multicenter trial investigated PD patients whose symptoms were not satisfactorily controlled by ropinirole, at a total daily dose of 3 mg to 12 mg, taken as monotherapy or as an adjunct to levodopa. Switching treatment from oral ropinirole to transdermal rotigotine was carried out overnight, with a dosage ratio of 1.5:1. After a 28-day treatment period, the safety and tolerability of switching was evaluated. Due to the exploratory nature of this trial, the effects of rotigotine on motor and nonmotor symptoms of PD were analyzed in a descriptive manner. RESULTS: Of the 116 subjects who received at least one treatment, 99 (85%) completed the 28-day trial period. Dose adjustments were required for 11 subjects who completed the treatment period. A total of 76 treatment-emergent adverse events (AEs) occurred in 45 subjects. No subject experienced a serious AE. Thirteen subjects discontinued rotigotine prematurely due to AEs. Efficacy results suggested improvements in both motor and nonmotor symptoms and quality of life after switching. Fifty-two subjects (46%) agreed that they preferred using the patch over oral medications, while 31 (28%) disagreed. CONCLUSIONS: Switching treatment overnight from oral ropinirole to transdermal rotigotine patch, using a dosage ratio of 1.5:1, was well tolerated in Korean patients with no loss of efficacy. TRIAL REGISTRATION: This trial is registered with the ClincalTrails.gov Registry (NCT00593606).

Hyperhomocysteinemia due to levodopa treatment as a risk factor for osteoporosis in patients with Parkinson's disease.

Parkinson's disease (PD) patients have been reported to have lower bone mineral density (BMD) and higher fracture risk than individuals without PD. We assessed the association between hyperhomocysteinemia due to levodopa intake and BMD in PD patients. We measured serum homocysteine (Hcy) concentrations and BMD in the proximal femur and lumbar spine of PD patients aged 55 years or older (n = 95) and three age-/gender-matched control subjects (n = 285). The prevalence of osteoporosis was higher in both men (2.5-fold) and women (1.7-fold) with PD than in controls, and adjusted odds ratios for osteoporosis were 3.57 (95% confidence interval [CI], 1.25-10.20) for men and 2.54 for women (95% CI, 1.31-4.93) with PD. Serum Hcy concentrations were significantly higher in PD patients (median = 13.0 micromol/l) than controls (median = 11.5 micromol/l) (P = 0.005). Serum Hcy concentrations were independently associated with BMD values at all proximal femur sites in all subjects (P = 0.005 to 0.012). In PD patients, higher serum Hcy concentrations were independently associated with higher fracture risk (P = 0.029). PD patients taking higher doses of levodopa had significantly higher serum Hcy concentrations (P = 0.013), and greater levodopa intake was associated with lower BMD values in some areas (P = 0.008 to 0.029). In conclusion, these findings indicate that hyperhomocysteinemia due to levodopa intake may be one additional risk factor for osteoporosis and fracture in PD patients. Reducing Hcy may be a therapeutic modality for treating osteoporosis in PD patients taking levodopa.

Homocysteine-lowering therapy or antioxidant therapy for bone loss in Parkinson's disease.

We investigated whether homocysteine (Hcy)- lowering therapy or an antioxidant prevented bone loss in Parkinson's disease (PD) patients taking levodopa. Forty-two PD patients with low bone mineral density (BMD) taking levodopa were randomly assigned to Hcy-lowering therapy (5 mg folate and 1500 microg vitamin B(12) daily), alpha-lipoic acid (alpha-LA) therapy (1200 mg daily), or control groups. Primary outcomes were BMD changes from baseline to 12 months. Secondary outcomes were changes in Hcy level, and C-telopeptide (CTX) levels at 12 months. Forty-one patients completed the study. Hcy-lowering therapy resulted in significantly greater BMD changes at the lumbar spine (4.4%), total femur (2.8%), and femur shaft (2.8%) than control (P = 0.005-0.023). BMD changes in the alpha-LA therapy group were similar to those of the control group, but changes at the trochanter (4.6%) were significantly greater in the alpha-LA therapy group than in the control group after adjustment for body mass index changes. Hcy concentrations decreased to 35.2% +/- 13.4% in the Hcy-lowering therapy group, but increased in other groups. Serum CTX levels at 12 months tended to be lower in the Hcy-lowering group (0.442 +/- 0.024 ng/mL) than control group (0.628 +/- 0.039 ng/mL) (P = 0.159). This small trial suggests that Hcy-lowering therapy may prevent bone loss in PD patients taking levodopa.

Comparison of Cerebral Glucose Metabolism between Possible and Probable Multiple System Atrophy.

BACKGROUND: To investigate the relationship between presenting clinical manifestations and imaging features of multisystem neuronal dysfunction in MSA patients, using (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET). METHODS: We studied 50 consecutive MSA patients with characteristic brain MRI findings of MSA, including 34 patients with early MSA-parkinsonian (MSA-P) and 16 with early MSA-cerebellar (MSA-C). The cerebral glucose metabolism of all MSA patients was evaluated in comparison with 25 age-matched controls. (18)F-FDG PET results were assessed by the Statistic Parametric Mapping (SPM) analysis and the regions of interest (ROI) method. RESULTS: The mean time from disease onset to (18)F-FDG PET was 25.9±13.0 months in 34 MSA-P patients and 20.1±11.1 months in 16 MSA-C patients. Glucose metabolism of the putamen showed a greater decrease in possible MSA-P than in probable MSA-P (p=0.031). Although the Unified Multiple System Atrophy Rating Scale (UMSARS) score did not differ between possible MSA-P and probable MSA-P, the subscores of rigidity (p=0.04) and bradykinesia (p= 0.008) were significantly higher in possible MSA-P than in probable MSA-P. Possible MSA-C showed a greater decrease in glucose metabolism of the cerebellum than probable MSA-C (p=0.016). CONCLUSIONS: Our results may suggest that the early neuropathological pattern of possible MSA with a predilection for the striatonigral or olivopontocerebellar system differs from that of probable MSA, which has prominent involvement of the autonomic nervous system in addition to the striatonigral or olivopontocerebellar system.

Analysis of PARK genes in a Korean cohort of early-onset Parkinson disease.

Mutations in five PARK genes (SNCA, PARKIN, DJ-1, PINK1, and LRRK2) are well-established genetic causes of Parkinson disease (PD). Recently, G2385R substitution in LRRK2 has been determined as a susceptibility allele in Asian PD. The objective of this study is to determine the frequency of mutations in these PARK genes in a Korean early-onset Parkinson disease (EOPD) cohort. The authors sequenced 35 exons in SNCA, PARKIN, DJ-1, PINK1, and LRRK2 in 72 unrelated EOPD (age-at-onset

One-year open-label study of entacapone in patients with advanced Parkinson disease.

BACKGROUND AND PURPOSE: A carboxy-O-methyl transferase inhibitor entacapone has been introduced as an adjuvant drug for Parkinson disease (PD) patients. Although clinical trials reported beneficial role of entacapone, a long-term trial over 3 years failed to show significant effect. The goals of this study were to evaluate the clinical benefit and the efficacy of entacapone in an open clinical practice. METHODS: After the completion of a double-blind placebo-controlled entacapone study, 149 patients from 4 centers were included. Antiparkinsonian medications were optimized by the judgment of the neurologists in charge. The clinical global impression (CGI) scale was obtained at 6 months and 1 year after the initiation of entacapone treatment. RESULTS: Of the 149 patients, 117 patients chose to try entacapone in an open-label fashion. Sixty-nine (59%) patients completed the 1-year trial. Twenty-nine patients discontinued entacpaone before 6 months, and 19 between 6 months and 1 year during trial. Twelve patients out of 48 patients discontinued entacapone because of its poor efficacy. The CGI scale was 3.9 (+/-1.5) at the beginning of the trial, 4.3 (+/-1.1) at 6 month, and 3.8 (+/-1.3) at 1 year, respectively. The CGI scale of those who discontinued between 6 month and 1 year was 3.4 (+/-1.7), which was worse, but insignificantly, than that of the continuer. CONCLUSIONS: The dropout at 1 year of our study was very high at 41%. Even though entacapone is indicated for advanced PD patients with motor fluctuation, the fluctuators commonly have dyskinesia and mental symptoms, which can become more troublesome with entacapone. In the patients with advanced PD, the clinical efficacy and side effects should be carefully considered in a long-term use of entacapone.

A novel missense mutation of the GTP cyclohydrolase I gene in a Korean family with hereditary progressive dystonia/dopa-responsive dystonia.

Hereditary progressive dystonia with marked diurnal fluctuation/dopa-responsive dystonia (HPD/DRD) shows the considerable heterogeneity of clinical phenotypic expression and a dramatic sustained response to levodopa. The autosomal dominant HPD/DRD is caused by mutations in the gene coding GTP cyclohydrolase I (GCH I), the enzyme that catalyzes the first step in the biosynthesis of tetrahydrobiopterin. Previous studies suggested that normal [18F]Dopa positron emission tomography or [123I]beta-CIT single-photon emission computed tomography (SPECT) imaging, indicating intact structural integrity of nigrostriatal neurons, may be useful for differentiating HPD/DRD from clinically similar conditions such as juvenile Parkinson's disease with dystonia that have a considerably poorer prognosis. We here report a Korean family affected with HPD/DRD due to a novel missense mutation of the GCH I gene (T-->G mutation in exon 2), Met 137 Arg, which may change the conformation of the binding site of GCH I. The clinical features are considerably variable within the family. We documented normal striatal uptake of [123I]IPT, a dopamine transporter ligand with fast washout kinetics, in our patients by using SPECT. This method can be helpful in diagnosing HPD/DRD in uncertain cases.