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.

Cerebral Air Embolism Following Pneumopyelography

No abstract available.

Factors Related to Quality of Life in Patients with Parkinson's Disease

BACKGROUND: The goal of therapeutic interventions for Parkinson's Disease (PD) is to improve the symptoms and mitigate the effect on the Quality of Life (QOL) in the individual patient. The purpose of this study was to investigate QOL and related factors in PD patients in Korea. METHODS: Between January 1, 2004 and July 15, 2004, eighty-one PD patients were included. The patients were assessed using Parkinson's Disease Quality of Life (PDQL), Modified Beck Depression Inventory (BDI), and K-MMSE. RESULTS: Twenty-five male and 56 female patients were included in the study. The mean age was 60.7 years and the mean disease duration was 7 years. The male patients (p=0.07) and young age at onset (p=0.07) showed borderline correlation with PDQL score. Medical cost for PD showed significant correlation with PDQL score (p<0.001). The patients working in the daytime or spending the daytime with their spouse showed significantly higher PDQL score than those who did not (p=0.01). Among the disease characteristics, the disease duration, levodopa dosage, UPDRS score, ADL, Hoehn and Yahr stage, the presence of motor fluctuation and dyskinesia, showed that depression had a strong correlation with the PDQL score (p<0.001). On the stepwise regression analysis, the most important factor was presence of depression, disease duration and the UPDRS total score in order of strength. CONCLUSIONS: The QOL in PD patients was strongly associated with depression, disease duration, and the severity of PD. We suggest that the assessment and proper management of depression as well as other PD symptoms is necessary to improve QOL of the PD patients.

Efficacy and Safety of Entacapone in the Patients with Parkinson's Disease Experiencing Wearing-off Phenomenon: Multicenter Randomized Placebo-controlled Double Blind Study

BACKGROUND: The purpose of this study was to assess the efficacy and safety of entacapone, a catechol-O-methyltransferase (COMT) inhibitor in Parkinson's disease (PD) patients with wearing-off phenomenon. METHODS: A total of 197 PD patients were included in this 2-month multi-center, randomized, placebo-controlled, double blind, parallel-group study. After a 2-week screening period, each patient was randomly allocated to receive either entacapone (n=98) or placebo (n=99) as an adjunct to levodopa. The efficacy was evaluated with the changes of "on" and "off" time percentage while awake, the reduction of the levodopa dose, Unified Parkinson's Disease Rating Scale (UPDRS), and the clinical global impression (CGI) by the examiner. RESULTS: The percentage of "on" time increased by 9.4 +/- 18.0% in the entacapone group, 7.4 +/- 15.6% in the placebo group. The percentage of "off" time was reduced by 8.6 +/- 16.9% in the entacapone group, 6.6 +/- 18.2% in the placebo group. These parameters did not show a statistical significance between the two groups. However, the levodopa dose was significantly reduced in the entacapone group (51.6 +/- 154.5 mg/day) compared with the placebo group (0.7 +/- 130.0 mg/day) (p=0.009). The total and motor scores of the UPDRS were significantly decreased in the entacapone group (p=0.039, p=0.017, respectively). The most common adverse drug reactions in the entacapone group were urine discoloration (22%), dyskinesia (13%), dizziness (7%). CONCLUSIONS: Entacapone was a safe and well-tolerated drug. Although the changes of "on" and "off" time were not significant, entacapone showed an overall significant beneficial effect in the PD patients with wearing-off phenomenon.

The Caregivers' Burden in Parkinson's disease

BACKGROUND: Caring for patients with Parkinson's disease (PD) is a burden to caregivers since currently available treatment modalities for PD depend on symptomatic treatments. However, there have only been a few studies regarding the caregivers of PD patients. The authors investigated the burden, depression, and anxiety of the caregivers of PD patients. METHODS: Fifty-three main caregivers of PD patients were included. The burden, anxiety, and depression of the caregivers were evaluated using the Zarit Burden Inventory (ZBI), the Spielberger State-trait Anxiety Inventory, and the Beck Depression Inventory. RESULTS: Twenty-one male and 32 female patients had a mean age 61.4 years and a mean disease duration of 7.5 years. The caregivers included 29 men and 24 women with a mean age of 55.8 years. The sex of the patients (male) and caregivers (female), the relation to the patient (daughter-in-law), and frequency of hospital visits were all significantly associated with the caregiver's burden. Among the disease characteristics, the duration, severity of PD, presence of motor fluctuation, and levodopa-associated confusion/hallucination affected the caregivers' burden significantly. The level of depression and anxiety was positively correlated with the level of burden. On a stepwise regression analysis, the significant predictors of the caregivers' burden were ADL, UPDRS IV, and state anxiety in order of strength. CONCLUSIONS: The caregivers' burden in PD was affected by various demographic and disease characteristics, which also correlated with the level of depression and anxiety. We suggest that comprehensive treatment strategies for PD should be developed for the caregivers as well as the patients.

A Case of Biopsy-proven Early-onset Alzheimer's Disease with Hemiparkinsonism

Patients with dementia and concomitant parkinsonism are frequently encountered in the elderly population. When it comes to young adults, however, coexistence of Alzheimer's disease (AD) and Parkinson's disease (PD) is rare. We described a case of 47-year old man with presenile onset dementia associated with hemiparkinsonism involving the right extremities. Brain biopsy showed neurofibrillary tangles and neuritic plaques, compatible with Alzheimer's disease. Iodine-123 labelled N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane ([(123)I]IPT) SPECT, dopamine transporter imaging, revealed a decreased uptake in both basal ganglia, more severe on the left side, particularly the caudal putamen, which is consistent with the finding of idiopathic Parkinson's disease. This case is unique in that damage on the nigrostriatal dopaminergic system in a patient with Alzheimer's disease was demonstrated by a functional neuroimaging study and that early-onset AD and early-onset PD, two rare conditions, coexist in the same individual.

A Case of Systemic Lupus Erythematosus Presenting with Chorea: Evidence for Striatal Hypermetabolism

Chorea is an uncommon clinical manifestation of Sytemic lupus erythematosus (SLE). Its pathogenic mechanism has not been clearly clarified. We report a 54-year-old woman with SLE who presented with generalized chorea as an initial manifestation. Fluorine-18-fluorodeoxyglucose (FDG) PET revealed increased metabolism in the bilateral putamen. Intravenous and oral administration of steroid markedly improved chorea. Hypermetabolism of the bilateral putamen diminished on follow-up FDG-PET after the disappearance of chorea. This study suggests that chorea in SLE is associated with striatal hypermetabolism.

Leaked CSF on Spine MRI in a Patient with Syndrome of CSF Hypovolemia

A 34-year-old woman was admitted because of severe orthostatic headache. On CSF examination, the opening pressure was below 30 mmH2O. A spine MRI showed a large collection of extradural fluid indicating that CSF leaked into the extradural space. The headache was resolved by an epidural blood patch. We present a patient with a syndrome of CSF hypovolemia, whose spine MRI showed a large amount of leaked CSF in the epidural space of the spine.

Clinical Outcomes of Simultaneous Bilateral Pallidotomy in Advanced Parkinson's Disease

OBJECTIVE: Pallidotomy is known to improve the symptoms of idiopathic Parkinson, s disease (PD), motor fluctuations and dyskinesia related to levodopa therapy. Previous studies reported significantly higher complication rates associated with bilateral pallidotomy than unilateral pallidotomy. The authors assess the safety and clinical outcomes of bilateral pallidotomy for advanced PD. METHODS: Simultaneous bilateral pallidotomy was performed in eight patients with advanced PD between January 1, 2001 and December 31, 2001. All patients underwent lesion making in posteroventral site of internal globus pallidus. The target was localized using macroelectrode stimulation and MRI guided stereotactic technique. The lesions were made by radiofrequency currents. RESULTS: Among eight cases, seven had severe disabling dyskinesias. Compared with baseline scores, the values of dyskinesia after surgery was significantly decreased (P<0.05) for up to 1 year. The mean score changed from 4.4+/-2.1 to 0.3+/-0.5. According to Unified Parkinson's Disease Rating Scale (UPDRS), the mean motor score in off period, which was 38.3+/-13.8 was significantly decreased for 6 months (P<0.05). The ADL (on/off) scores and motor "on" scores of UPDRS were unchanged or deteriorated to 12 months after surgery. There was no apparent adverse effect after surgery in all patients. Only transient mild dysphagia happened in one patient. CONCLUSION: Simultaneous bilateral pallidotomy in advanced PD appears to be effective and safe, particularly in reducing the dyskinesia; in our experience, the side effects are not as high as reported by other groups.

Penicillamine Induced Breast Enlargement in a Patient with Wilson's Disease

No abstract available.

Chorea in Systemic Lupus Erythematosus: Evidence for Bilateral Putaminal Hypermetabolism on F-18 FDG PET / 대한핵의학회잡지

PURPOSE: We describe a 54-year-old woman with systemic lupus erythematosus (SLE) who suddenly presented with chorea and had positive antiphospholipid antibodies. F-18 FDG PET showed abnormally increased glucose metabolism in bilateral putamen and primary motor cotex. Tc-99m ECD SPECT also showed abnormally increased regional cerebral blood flow in bilateral putamen. She was treated with corticosteroid and aspirin after which the symptoms improved. Four months later, follow up F-18 FDG PET showed improvement with resolution of hypermetabolism in bilateral putamen. This case suggests that striatal hypermetabolism is associated with chorea in SLE.

The DYT1 Gene Mutation in Primary Torsion Dystonia without Familial Background

BACKGROUND: The DYT1 dystonia is primary torsion dystonia (PTD) caused by a GAG deletion in DYT1 gene on chromosome 9 and transmits as autosomal dominant trait. It usually begins as limb-onset dystonia in childhood and tends to spread to other sites and has been reported as the most common cause of early onset PTD in Ashkenazi Jews. However, the frequency of DYT1 mutation in Korean patients with sporadic PTD has not been reported. METHODS: We examined dystonia patients who visited the Neurologic Clinic of Asan Medical Center between Jan 2001 and March 2002. The sporadic PTD patients of them were screened by genotyping with their peripheral blood samples. RESULTS: The 66 patients with sporadic PTD were recruited and two of them showed DYT1 mutation on Chromosome 9. One patient had segmental dystonia with cervical onset; the other had generalized dystonia with left leg onset. None of the patients with focal dystonia showed a DYT1 mutation. CONCLUSIONS: The DYT1 dystonia comprise a small portion of PTD without familial history in Korea. The DYT1 gene test should be considered in the early-onset or spreading type dystonia despite the absence of familial background in primary dystonia patient.

A Case of Dementia related to AIDS

We report a patient with AIDS, who initially presented with progressive cognitive impairment and gait disturbance. A T2-weighted brain MRI demonstrated multiple hyperintensities in bilateral periventricular white matter, thalami, brainstem, cerebellum, and left temporo-occipital white matter. Enzyme-linked immunosorbent assay and Western blot for HIV were positive. The CD4+ T-cell count was 158 cells/mm3 and the plasma HIV RNA level was 65, 000 copies/mL. Highly active antiretroviral therapy was administered.

A Case of Metastatic Non-small Cell Lung Cancer Presenting with Numb Chin Syndrome / 결핵

Numb chin syndrome is a rare clinical manifestation, characterized by focal sensory loss and paresthesia of the chin. It is more often associated with cancer than with benign disorders, and can be the first manifestation of a cancer. A 60-year-old man presented with focal numbness of right chin and gingiva for 10 days. Chest computed tomography showed a 3 cm sized mass on the distal left main-stem bronchus. Squamous cell carcinoma was diagnosed on bronchoscopic biopsy. However, bony metastasis of mandible was not evident on reontgenogram, CT scan, bone scintigram and positron emission tomography. Despite the chemotherapy with three cycles of paclitaxel and cisplatinum, the cancer was progressed and pain on the right chin was developed 4 months .later. Bone scintigram showed multiple bony metastasis including mandible. Here we report this case with a brief review of the appropriate literature.

Treatment of Parkinson's Disease

No abstract available.

Ropinirole as an Adjunct to Levodopa in the Treatment of Parkinson's Disease

BACKGROUND: Ropinirole is a non-ergoline D2 agonist which has a highly selective affinity to D2 receptor. The aim of this study was to evaluate the efficacy and safety of ropinirole in the treatment of Parkinson's disease (PD). METHODS: Seventy-six cases 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) over a 16-week period. All subjects were not optimally controlled on levodopa due to motor fluctuations. The response rate was defined as the percentage of patients who had at least 20% reduction of levodopa doses. The clinical status was also assessed using the Unified Parkinson's Disease Rating Scale (UPDRS), Clinical Global Impression (CGI), and reduction of off durations. RESULTS: The end-point analysis, on an intention-to-treat basis, revealed significantly higher response rate in the ropinirole group compared with the bromocriptine group (odds ratio 2.995, 95% C.I. (1.157, 7.751)). A statistically significant improvement in CGI was also observed in the ropinirole group (p=0.046). The mean off duration was significantly reduced in the ropinirole group (p=0.0001). Other parameters using the UPDRS motor score or off duration did not show significant differences between the two groups. The overall incidence of adverse effects was not significantly different between the two groups. The most common side effects were dizziness, dyskinesia, and nausea/vomiting. No subjects were withdrawn from the study due to side effects. CONCLUSION: Ropinirole is a safe and well-tolerated drug and provides superior overall efficacy compared with bromocriptine as an adjunct to levodopa. (J Korean Neurol Assoc 19(2):102~109, 2001)

Ropinirole as an Adjunct to Levodopa in the Treatment of Parkinson's Disease

BACKGROUND: Ropinirole is a non-ergoline D2 agonist which has a highly selective affinity to D2 receptor. The aim of this study was to evaluate the efficacy and safety of ropinirole in the treatment of Parkinson's disease (PD). METHODS: Seventy-six cases 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) over a 16-week period. All subjects were not optimally controlled on levodopa due to motor fluctuations. The response rate was defined as the percentage of patients who had at least 20% reduction of levodopa doses. The clinical status was also assessed using the Unified Parkinson's Disease Rating Scale (UPDRS), Clinical Global Impression (CGI), and reduction of off durations. RESULTS: The end-point analysis, on an intention-to-treat basis, revealed significantly higher response rate in the ropinirole group compared with the bromocriptine group (odds ratio 2.995, 95% C.I. (1.157, 7.751)). A statistically significant improvement in CGI was also observed in the ropinirole group (p=0.046). The mean off duration was significantly reduced in the ropinirole group (p=0.0001). Other parameters using the UPDRS motor score or off duration did not show significant differences between the two groups. The overall incidence of adverse effects was not significantly different between the two groups. The most common side effects were dizziness, dyskinesia, and nausea/vomiting. No subjects were withdrawn from the study due to side effects. CONCLUSION: Ropinirole is a safe and well-tolerated drug and provides superior overall efficacy compared with bromocriptine as an adjunct to levodopa. (J Korean Neurol Assoc 19(2):102~109, 2001)

Familial Writer's Cramp with DYT1 Mutation: A Clinical and Genetic Analysis of a New Kindred

BACKGROUND: Recently a non-Jewish German family with writer's cramp was reported to have DYT1 mutation, expanding the phenotypic spectrum of DYT1. Although functional brain surgery has been tried for generalized dystonia, surgical outcome in focal dystonia patients with DYT1 mutation has not yet been reported. We investigated the clinical features and response to thalamotomy in familial writer's cramp with DYT1 mutation. METHODS: Family members were examined and clinically affected cases were video-taped. For the detection of DYT1 mutation, PCR-RFLP(restriction fragment length polymorphism) and heteroduplex analyses were performed as screening tests. Additional DNA sequencing was performed for the proband case to confirm the GAG deletion. RESULTS: Among this clinically homogeneous non-Jewish Korean family, five members in three generations were affected. Age of onset ranged from 7 to 20 years. Writing difficulty was the initial and the main disabling problem for all the affected individuals. All had the bilateral writer's cramp in succession. Dystonia remained focal and task-specific for the entire period after onset. Unilateral thalamotomy was performed in three patients, with remarkable improvement. Surgical benefit remained unchanged during the follow-up period of 6-8 years. DYT1 mutation cosegregated with the affected members. CONCLUSIONS: This study adds another evidence that DYT1 phenotype can present with purely focal and task-specific dystonia in all the affected members of a family. Marked and sustained improvement following thalamotomy in three of our patients suggests that stereotaxic thalamotomy is beneficial in familial focal dystonia with DYT1 mutation. (J Korean Neurol Assoc 19(2):110~115, 2001)

Familial Writer's Cramp with DYT1 Mutation: A Clinical and Genetic Analysis of a New Kindred

BACKGROUND: Recently a non-Jewish German family with writer's cramp was reported to have DYT1 mutation, expanding the phenotypic spectrum of DYT1. Although functional brain surgery has been tried for generalized dystonia, surgical outcome in focal dystonia patients with DYT1 mutation has not yet been reported. We investigated the clinical features and response to thalamotomy in familial writer's cramp with DYT1 mutation. METHODS: Family members were examined and clinically affected cases were video-taped. For the detection of DYT1 mutation, PCR-RFLP(restriction fragment length polymorphism) and heteroduplex analyses were performed as screening tests. Additional DNA sequencing was performed for the proband case to confirm the GAG deletion. RESULTS: Among this clinically homogeneous non-Jewish Korean family, five members in three generations were affected. Age of onset ranged from 7 to 20 years. Writing difficulty was the initial and the main disabling problem for all the affected individuals. All had the bilateral writer's cramp in succession. Dystonia remained focal and task-specific for the entire period after onset. Unilateral thalamotomy was performed in three patients, with remarkable improvement. Surgical benefit remained unchanged during the follow-up period of 6-8 years. DYT1 mutation cosegregated with the affected members. CONCLUSIONS: This study adds another evidence that DYT1 phenotype can present with purely focal and task-specific dystonia in all the affected members of a family. Marked and sustained improvement following thalamotomy in three of our patients suggests that stereotaxic thalamotomy is beneficial in familial focal dystonia with DYT1 mutation. (J Korean Neurol Assoc 19(2):110~115, 2001)

Dentatorubro-pallidoluysian Atrophy: The Clinical and Molecular Genetic Study of Three Korean Families

Dentatorubro-pallidoluysian atrophy (DRPLA) is a rare neurodegenerative disorder with various clinical phenotypes and has a cytosine-adenine-guanine (CAG) trinucleotide repeat in a gene on chromosome 12. It has been known that trinucleotide repeat disorders show strong inverse correlations between the CAG repeat number and the age of onset and genetic anticipation. The purpose of this study was to investigate whether these observations are applicable to Korean patients. This report involved three Korean families and had on file the history of the 15 affected family mem-bers .Seven of the affected members had the diagnosis of DRPLA which was confirmed by a gene study. We observed inverse correlations between the CAG repeat number and the age of onset and genetic anticipation with high intra- and interfamilial variations. Although our study was in general agreement with previously documented features of DRPLA, some features could not be explained by currently understood pathophysiologic mechanisms.