Joong-Seok Kim

Poststroke Restless Legs Syndrome and Lesion location : Anatomical Considerations

Several case studies have reported on restless legs syndrome (RLS) associated with stroke. In this study, we investigated the prevalence and the lesion topography of poststroke RLS. There were 137 patients with ischemic stroke included in this study. The diagnosis of RLS was made 1 month after the index stroke using the criteria established by the International RLS Study Group. All patients enrolled underwent magnetic resonance imaging within 7 days of the onset of the stroke. The prevalence of stroke‐related RLS was calculated, and the topography of the associated ischemic lesions was analyzed. Among 137 patients, 17 patients (12.4%) were diagnosed with RLS after a stroke. Stroke‐related RLS was found in 10 out of 33 patients with a basal ganglia/corona radiata infarct (30.3%), 1 out of 8 patients with an internal capsular infarct (12.5%), and 1 out of 7 patients with a thalamic infarct (14.3%). In addition, one out of 54 with a cortical lesion with/without subcortical involvement (1.9%), and 4 out of 18 patients with a pontine lesion (22.2%) had RLS. The analysis of the lesions in the cortical and subcortical group showed only 1 patient in the cortical group had stroke‐related RLS, whereas 16 in the subcortical group had stroke‐related RLS. The results of this study suggest that lesions of the subcortical brain areas such as the pyramidal tract and the basal ganglia‐brainstem axis, which are involved in motor functions and sleep‐wake cycles, may lead to RLS symptoms in patients after an ischemic stroke.

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 ≤50) recruited from ten movement disorders clinics in South Korea. Gene dosage change of the aforementioned genes was studied using multiple ligation-dependent probe amplification. We found four patients with PARKIN mutations, which were homozygous deletion of exon 4, compound heterozygous deletion of exon 2 and exon 4, heterozygous deletion of exon 4, and heterozygous nonsense mutation (Q40X). Four patients had PINK1 mutations; a compound heterozygous mutation (N367S and K520RfsX522) and three heterozygous mutations (G32R, R279H, and F385L). A missense mutation of SNCA (A53T) was found in a familial PD with autosomal dominant inheritance. Nine patients (12.5%) had heterozygous G2385R polymorphism of LRRK2, whereas none had G2019S mutation. However, no mutations were detected in DJ-1 and UCHL1 in our series. We identified genetic variants in PARKIN, PINK1, LRRK2, and SNCA as a cause or genetic risk factors for PD in 25% of Korean EOPD, and mutation of PARKIN was the most common genetic cause.

Association of Vitamin D Receptor Gene Polymorphism and Parkinson's Disease in Koreans

1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), which is the biologically active form of vitamin D, has anti-inflammatory effects and can prevent experimental Parkinsons disease (PD). 1,25(OH)2D3 exerts most of its actions only after it binds to its specific nuclear receptors. Eighty-five Korean patients with PD and 231 unrelated healthy individuals were evaluated to determine if vitamin D receptor gene (VDRG) BsmI polymorphisms were markers for the susceptibility to PD in Korean patients. Each polymorphism was detected using polymerase chain reaction (PCR)-based restriction analysis. In addition, the relationship between the BsmI polymorphisms and the clinical manifestations of PD was evaluated. Overexpression of the b allele (91.2 vs. 85.7%; p=0.069) and homozygote bb (84.7 vs. 72.7%; p=0.043) was found in the PD patients compared with the controls. These results show for the first time an association between PD and a VDRG polymorphism, which might be involved in the pathogenesis of PD, or in the linkage disequilibrium of the VDRG to another pathogenic gene locus.

Association of cognitive dysfunction with neurocirculatory abnormalities in early Parkinson disease

Objective: Cognitive impairment and neurocirculatory abnormalities such as orthostatic hypotension (OH), supine hypertension (SH), and failure to decrease blood pressure at night (nondipping) occur relatively commonly in Parkinson disease (PD); however, whether cognitive dysfunction in early PD is related to neurocirculatory abnormalities has not been established. Cognitive dysfunction in PD is associated with white matter hyperintensities on MRI. We report results of an analysis of neuropsychological and hemodynamic parameters in patients with early PD. Methods: Among 87 patients, 25 had normal cognition, 48 had mild cognitive impairment, and 14 had dementia, based on comprehensive neuropsychological tests. Orthostatic vital signs and ambulatory 24-hour blood pressure monitoring were recorded, and brain magnetic resonance scans were obtained for all patients. Results: Cognitive impairment was associated with OH, SH, and white matter hyperintensities but not with nondipping. Dementia and white matter hyperintensities were common in SH. Of 13 patients with OH + SH, every one had mild cognitive impairment or dementia. Conclusions: Cognitive dysfunction is related to neurocirculatory abnormalities, especially OH + SH, in early PD, raising the possibility that early detection and effective treatment of those abnormalities might slow the rate of cognitive decline.

Detection of Human Herpesvirus 6 Variant A in Peripheral Blood Mononuclear Cells from Multiple Sclerosis Patients

Several authors report that human herpesvirus 6 (HHV-6) variants have different epidemiologies, in vivo tropism and pathogenic potentials. However, it is not well known what pathogenic roles its neurotropism might have in the variant type. As some active plaques of multiple sclerosis (MS) brain tissue harbor HHV-6 DNA divergent from the prototype virus, the possibility that the variant strain may play a role in the pathogenesis of MS has been suggested. Therefore, we tried to investigate the role of HHV-6 variants in the pathogenesis of MS. As HHV-6 is predominantly a T-cell-tropic virus, we examined HHV-6 DNA sequences in peripheral blood mononuclear cells (PBMC) from 34 MS patients, 6 with idiopathic transverse myelitis, 2 with optic neuritis and 20 healthy controls. Nested polymerase chain reaction was used to detect the HHV-6 genome. To discern HHV-6 variants A and B, amplification products were digested by restriction enzyme. We found that 7 of 34 MS patients and 2 of 6 patients with idiopathic transverse myelitis had the HHV-6 genome. On the contrary, there was no HHV-6 genome in the control group. All genomic sequences were of HHV-6 variant A (HHV-6A). Our results suggest that the detection of HHV-6A in the PBMC of patients with MS may raise the possibility of a relationship between latent HHV-6A infection and the pathogenesis of MS.

Influence of white matter hyperintensities on the cognition of patients with Parkinson disease.

BackgroundWhite matter hyperintensities (WMH) have been associated with cognitive impairment in elderly persons and in patients with Alzheimer disease. However, the role of WMH in Parkinson disease (PD) dementia remains to be elucidated. MethodsThe cohort for this study comprised 71 consecutive patients with PD, all of whom completed a clinical assessment, neuropsychologic investigation, and magnetic resonance imaging of brain. WMH were rated using the semiquantitative visual rating system proposed by Scheltens et al. ResultsThe PD dementia group had significantly more WMH than the PD without dementia group in the evaluated brain regions except for the infratentorial area. The WMH showed a significant correlation with age, Unified Parkinsons Disease Rating Scale, Mini-Mental State Examination, sum of the box of Clinical Dementia Rating, and many of the cognitive domains. The linear regression model showed that the WMH was independently associated with cognitive impairment in patients with PD, regardless of age, sex, duration or severity of PD symptoms, and vascular risk factors. ConclusionsThese findings confirm that WMH might be associated with cognitive decline in patients with PD, regardless of age, sex, education status, duration or severity of PD symptoms, and vascular risk factors. This result suggests that other nonvascular factors contribute to the progression of dementia in patients with PD.

The prevalence and patterns of pharyngoesophageal dysmotility in patients with early stage Parkinson's disease†

Dysphagia occurs in the majority of patients with Parkinsons disease (PD) and is known to correlate with abnormalities of oropharyngeal function. The aim of this study was to evaluate pharyngoesophageal activity in patients with early‐stage PD. Newly diagnosed PD patients with a symptom duration not exceeding 3 years were included. All PD patients were questioned about symptoms of dysphagia and underwent combined multichannel intraluminal impedance manometry and multiple rapid swallow tests. Fifty‐four patients (22 men and 32 women, 67.1 ± 10.3 years) were enrolled. The duration of Parkinsonian motor symptoms was 11.5 ± 8.8 months, the Hoehn and Yahr stage was 1.6 ± 0.4, and the total Unified Parkinsons Disease Rating Scale was 25.1 ± 18.6. Esophageal manometry in the liquid swallow and viscous swallow tests was abnormal in 22 (40.7%) and 31 (67.4%) patients, respectively. Although manometric abnormalities were more common in patients with more severe dysphagia symptoms, many patients with no or minimal symptoms also had manometric abnormalities. Repetitive deglutition significantly correlated with failed peristalsis and incomplete bolus transit. Abnormal responses to multiple rapid swallow tests were found in 33 out of 54 patients; 29 with incomplete inhibition (repetitive contraction) and 4 with failed peristalsis. These results suggest that the majority of patients with early‐stage PD showed pharyngeal and esophageal dysfunction even before clinical manifestations of dysphagia, which may reflect selective involvement of either the brain stem or the esophageal myenteric plexus in early‐stage PD.

A randomized crossover comparative study of aspirin, cilostazol and clopidogrel in normal controls: analysis with quantitative bleeding time and platelet aggregation test

The effects of three antiplatelet drugs, aspirin, clopidogrel and cilostazol, were examined and compared using a quantitative bleeding time (QBT) test apparatus. In 12 healthy adult male subjects, a QBT test and platelet aggregation test were performed before and after medication. Cilostazol was found to be as effective as aspirin and clopidogrel in inhibiting platelet aggregation. Following the oral administration of aspirin and clopidogrel for 7 days, the bleeding time was significantly prolonged. In contrast, none of these QBT parameters were altered by the cilostazol treatment. This suggests that cilostazol has potent efficacy in inhibiting platelet aggregation without prolonging the bleeding time and changing the bleeding pattern.

Relationship between High-Sensitivity C-Reactive Protein and Clinical Functional Outcome after Acute Ischemic Stroke in a Korean Population

Background: High-sensitivity C-reactive protein (hs-CRP) has been shown to be a powerful predictor of coronary ischemic events. However, the prognosis of functional disability in patients with cerebrovascular disease has not been well established. Therefore, we performed this study to determine the prognostic significance of hs-CRP levels in patients with functional disability after acute ischemic stroke. Methods: A total of 417 Korean patients with ischemic stroke were examined within 24 h after symptom onset. hs-CRP measurements were obtained on admission and on the seventhhospital day. The correlations between the concentration of hs-CRP and functional disability duration 12 months after stroke onset were analyzed. Results: The present study showed that hs-CRP levels on admission and on the seventh hospital day were significantly correlated with the modified Rankin Scale (mRS) score 12 months after stroke onset. These results also demonstrated that mRS scores are more closely associated with hs-CRP levels on the seventh hospital day than hs-CRP levels on admission. Conclusion: This study demonstrated that elevated hs-CRP levels on the seventh hospital day, rather than within 24 h after stroke onset, could strongly predict the prognosis of functional disability. These results supported that hs-CRP is a useful marker of ischemic stroke in the Korean population.

Cardiac 123I-MIBG scintigraphy in patients with drug induced parkinsonism

Cardiac sympathetic dysfunction was investigated using 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy in 20 patients with drug induced parkinsonism (DIP). The mean heart to mediastinum ratio was significantly greater in patients with DIP than in those with Parkinson’s disease (mean (SD): 2.07 (0.39) v 1.28 (0.15), p<0.001). MIBG uptake was not different between the DIP patients and controls. Two DIP patients whose MIBG uptake was significantly reduced showed persistent parkinsonism and responded dramatically to levodopa.