Sang-Myung Cheon

Changes in platelet P-selectin and in plasma C-reactive protein in acute atherosclerotic ischemic Stroke treated with a loading dose of clopidogrel

AbstractBackground: The surface expression of P-selectin on platelets contributes to the progression of inflammatory processes and thrombosis in atherothrombosis. In this study, we showed that the combination regimen of clopidogrel with aspirin could downregulate the P-selectin expression on platelets and the plasma concentration of C-reactive protein (CRP) in acute stage of atherosclerotic ischemic stroke. Methods: Patients with acute ischemic stroke (<24 hours) were randomized for 7 days to combined regimen of clopidogrel and aspirin (n = 24) or intravenous heparin with aspirin (n = 28). We measured the changes of National Institute of Health Stroke Scale (NIHSS) scores, CRP concentration, and surface expressions of P-selectin on platelets during 7 days. Results: The combined regimen of clopidogrel and aspirin significantly reduced platelet P-selectin expression (93.6 ± 16.6, p < 0.01) and plasma concentration of CRP (1.2 ± 1.5 mg/dl, p < 0.01) after 7 days of stroke onset compared with the values (P-selectin; 115.5 ± 20.7, CRP; 2.5 ± 2.8 mg/dl) of initial 24 hr. Also, the clinical improvement, as measured by NIHSS score, was significant in the clopidogrel loading group at 7 days (6.2 ± 5.5, p < 0.05) compared to the initial 24 hrs (10.1 ± 7.6). Conclusion: Our results indicate that the combined regimen of clopidogrel and aspirin has beneficial effects on regulating platelet activation and inflammatory processes in acute atherosclerotic ischemic stroke. Thus, this combination regimen deserves further evaluation in clinical trial for the treatment of acute atherosclerotic ischemic stroke.

A Case of Gerstmann-Sträussler-Scheinker Disease

Background Gerstmann-Sträussler-Scheinker disease (GSS) is a type of human transmissible spongiform encephalopathy (TSE) that is determined genetically. Case Report A 46-year-old woman presented with a slowly progressive ataxic gait and cognitive decline. She was alert but did not cooperate well due to severe dementia and dysarthria. High signal intensities in the cerebral cortices were evident in MRI, especially in diffusion-weighted images (DWI). A prion protein gene (PRNP) analysis revealed a P102L (proline-to-leucine) mutation in codon 102. Conclusions This is the first reported case of GSS (confirmed by PRNP analysis) in Korea. Distinctive MRI findings are also presented.

Selective Susceptibility of Human Dopaminergic Neural Stem Cells to Dopamine-Induced Apoptosis

Dysfunctions of ubiquitin-proteasome system and toxicity of dopamine have been known as the key mechanisms in the pathogenesis of Parkinsons disease (PD) and proteasome inhibitors are widely used in experimental models of PD to reproduce cell death of dopaminergic neurons. In the present study, immortalized human neural stem cells (HB1.F3, F3) and those transfected with human aromatic acid decarboxylase gene (F3.AADC), were used to investigate the mechanism of selective dopaminergic neuronal cell death mediated by dopamine or proteasome inhibitors. Flow cytometric analysis revealed that F3.AADC was more susceptible to dopamine than parental F3 cell which does not carry dopaminergic phenotype. The dopamine-induced apoptosis was mediated by activation of caspases 3 and 9 and cleavage of PARP. Proteasome inhibitors also induced apoptosis in dose-dependent manner but there was no difference between cell types. Prolonged exposure to subtoxic dose of proteasome inhibitors further enhanced dopamine-induced apoptosis in the F3.AADC, and increased presence of alpha-synuclein and ubiquitin-positive inclusions was noted in the cytoplasm of apoptotic cells by immunocytochemistry. These findings indicate that dopaminergic cells are selectively susceptible to dopamine toxicity and prolonged suppression of proteasome system further enhances selective sensitivity to dopamine toxicity. Chronic subtoxic proteasomal dysfunction of dopaminergic cells might contribute to selective cell death of dopaminergic neurons during the pathogenesis of Parkinsons disease.

Orthostatic Hypotension and Cognitive Impairment in De Novo Patients with Parkinson’s Disease

A relationship between orthostatic hypotension (OH) and cognitive dysfunction in Parkinson’s disease (PD) has been recently investigated[1-3]. Most of the previous studies were performed with patients taking anti-parkinsonian medications, and one study was performed in patients before medication included patients with dementia. The authors studied OH in drug-naive and non-demented patients with PD[4]. To find the relationship between cognitive dysfunction and OH, we performed an additional analysis of the association between cognitive function and OH in our cohort of PD patients[4]. The clinical characteristics of the subjects (45 drug-naive PD patients, 17 men and 28 women, age of 63.8 ± 10.1 years, disease duration of 1.3 ± 1.1 years) and assessment of OH were described in a previous report[4]. Briefly, OH was measured by monitoring systolic and diastolic blood pressure (BP) using a tilt table. After a 10 minute period of lying down, the table was tilted to 60° upright, and the BP was recorded at the first, third, and fifth minutes after tilting. OH was defined as a drop in systolic BP ≥ 20 mm Hg or in diastolic BP ≥ 10 mm Hg at any time following being uprighted[2]. A detailed cognitive assessment was performed using the Seoul Neuropsychological Screening Battery (SNSB)[5]. Abnormal results of the SNSB were determined by a comparison with the results of a standard control group (less than 1 standard deviation) in each of six domains (attention, language, calculation, visuospatial function, memory, and frontal/executive function). SPSS version 19 for Windows (SPSS Inc., Chicago, IL, USA) was used for the statistical calculations. The Mann-Whitney and chi tests were employed to analyze intergroup difference. Statistical significance was declared at the p < 0.05 level. The results showed that nearly all patients (43/45, 95.6%) had an abnormality in at least one cognitive domain. Thirty five patients (77.8%) showed multiple domain abnormalities. Because all the participants did not show any impairment in the activities of daily living due to cognitive dysfunction, those patients with abnormal results could be classified as having mild cognitive impairment (MCI). Frontal/executive function was the most frequent abnormal domain (71.1%), followed by memory (66.7%), calculation (51.1%), and attention (44.4%). Abnormal results in patients with OH were more common in attention, memory, and frontal/executive function tests compared with those in patients without OH, but the differences were not significant. The overall performance of the patients showed no differences in terms of OH, but in the memory domain, the OH group showed significantly poorer performance in the recognition test of verbal memory than the normotensive group (Table 1). A similar non-significant trend was observed in the recognition test of visual memory. Discrimination tasks of recognition were also decreased in the OH group, and those differences became clear when the values were switched to percentiles of the general population (data not shown). There was no difference in the results of the cognitive function tests for those patients without any other comorbid disorders (data not shown). Table 1. Results of cognitive function tests in drug-naive and non-demented PD patients Several cognitive domains were reported to be associated with OH in PD, such as attention, visuospatial function and verbal memory. Memory was the most consistent domain throughout the reports, and in particular, verbal memory was the only domain associated with OH in the patients before medication[2]. Our results also revealed an association between OH and verbal memory dysfunction, but with respect to recognition rather than recall. Because recognition has been known to be preserved in PD patients, the poor performance in the recognition task by PD patients with OH would suggest that OH could contribute to temporal cortical dysfunction[6]. OH results in transient or sustained cerebral hypoperfusion and is associated with the presence of white matter lesions[2]. However, another study failed to find any difference in white matter lesions between patients with and without OH[3]. Although the role of ischemic burdens in OH has still not been established, OH could be a potential therapeutic target for the prevention of dementia in PD patients and warrants early detection and appropriate management. However, cognitive dysfunction and autonomic dysfunction, such as OH, can be a clinical marker for more extensive Lewy body pathology. Further studies should allocate the OH in the pathological context of PD and the clinical implications. There are several limitations in this report. We excluded PD patients with dementia, but detailed cognitive assessment revealed cognitive dysfunction in nearly all PD patients (43/45) compared with the age- and education-matched standard population. Although the prevalence of MCI in PD patients varies considerably depending on the report, there could be a selection bias in the setting of a tertiary referral hospital[7]. Another limitation is the clinical diagnosis of the patients. For diagnostic accuracy of PD, we enrolled PD patients who were followed up more than six months after the diagnosis of the patients. However, patients with atypical parkinsonism, especially multiple system atrophy and diffuse Lewy body disease, may have been included in our study. We did not control the medication for comorbid disorders, such as hypertension and benign prostate hypertrophy, which might have influenced the BP results. In conclusion, we found that OH was associated with cognitive dysfunction, especially the verbal memory task. The early detection and appropriate management of OH could have potential for the prevention of cognitive deterioration in patients with PD.

Effect of Carotid Artery Stenting on Cognitive Function in Patients with Carotid Artery Stenosis: A Prospective, 3-Month-Follow-Up Study

Background and Purpose Carotid artery stenting (CAS) is emerging as an alternative to carotid endarterectomy for the treatment of carotid artery stenosis (CS), but the effect of CAS on the cognitive function of patients with severe CS has not been fully investigated. The aim of this study was to use comprehensive neuropsychological tests to determine the effect of CAS on cognitive function from baseline to 3 months postprocedure in patients with severe CS. Methods Thirty-one patients due to undergo CAS due to high-grade CS (≥70%) and 11 control subjects who were diagnosed with CS, but who did not undergo CAS, and who visited the clinic or emergency room between February 2009 and February 2012 were recruited consecutively at baseline (i.e., pre-CAS). Follow-up neuropsychological evaluations after 3 months were completed by 23 of the 31 patients who underwent CAS, and by 10 of the 11 control subjects. The primary cognitive outcome was assessed using a neuropsychological test containing subcategories designed to test general cognitive function, attention, visuospatial function, language and related functions, memory, and frontal lobe/executive function. Results Of the 23 patients undergoing CAS who completed the 3-month follow-up tests, 12 had asymptomatic CS. During the 3-month follow-up period, the patients who underwent CAS and those with asymptomatic CS achieved similar results to the control group on all cognitive tests. However, symptomatic CS patients (n=11) who underwent CAS exhibited improvements in visuospatial function (p=0.046) and total Seoul Neuropsychological Screening Battery-Dementia Version scores (p=0.010) in comparison with both the asymptomatic CS patients and the control group. Conclusions The findings of this study suggest that CAS has a positive effect on cognitive function in patients with symptomatic CS over a 3-month follow-up period. A long-term, multicenter, prospective case-control study would be helpful to predict quality of life and prognoses for patients undergoing CAS.

Orthostatic hypotension in drug-naive patients with Parkinson's disease.

Background and Purpose Orthostatic hypotension (OH) is known to be present even in patients with early Parkinson’s disease (PD). To affirm the presence of OH and find correlation between OH and other dysautonomic symptoms in PD, this study has done in newly-diagnosed PD patients. Methods Forty-five non-demented patients with no prior history of treatment for PD were recruited (17 men, 63.8 ± 10.1 years of age). All the patients were evaluated for OH before starting medications. Autonomic symptoms were evaluated with structured questionnaires. Clinical characteristics of PD were evaluated (median Hoehn and Yahr stage 2.0 (1–3), 1.3 ± 1.1 years of disease duration), and comorbid medical conditions that could affect blood pressure were also recorded. Results OH was prevalent, and eighteen patients (40%) showed orthostatic hypotension, and twenty-seven (60%) did not (normotensive group). There was no significant difference in demographic and clinical characteristics between groups. The presence or severity of symptoms of autonomic dysfunction in the OH group also not differed from those of the normotensive group. Conclusions OH was prevalent even in the early stage of PD, and was not related to presence or severity of any other symptoms of autonomic dysfunction. Our findings suggest that clinicians should pay attention to OH from the early stage of disease.

Evaluation of the turning characteristics according to the severity of Parkinson disease during the timed up and go test

BackgroundPatients with Parkinson disease (PD) experience problems such as falls and freezing of gait during walking and turning in daily activities. However, few studies have examined the relationship between simultaneous turning tasks and the severity of PD.AimTo investigate turning characteristics in patients with PD using three-dimensional (3D) analysis during the timed up and go (TUG) test.MethodsThirty individuals performed the TUG test under 3D motion analysis: 10 patients with Hoehn and Yahr (H&Y) stages 2.5 and 3.0 PD (group I), 10 patients with H&Y stage 2.0 PD (group II), and 10 healthy older adult controls. Spatiotemporal and kinematic variables were analyzed during the TUG test with a Vicon 3-D motion analysis system.ResultsThe walking speed, step length, step length asymmetry index, range of motion of the hip, knee, and shoulder joints, and foot clearance height significantly differed between patients with PD and the controls. The step length and foot clearance height were significantly different between groups I and II.DiscussionThe step length and foot clearance are different between the severity levels of PD, and the TUG test may be useful for identifying turning characteristics in patients with PD.ConclusionsPatients with PD exhibited significant differences in all variables of interest compared to the controls. The step length and foot clearance height as well as the TUG test during the turning phase may be helpful for measuring turning in patients with different severity levels of PD.

Genetics of Parkinson's disease - a clinical perspective.

Discovering genes following Medelian inheritance, such as autosomal dominant-synuclein and leucine-rich repeat kinase 2 gene, or autosomal recessive Parkin, P-TEN-induced putative kinase 1 gene and Daisuke-Junko 1 gene, has provided great insights into the pathogenesis of Parkinson’s disease (PD). Genes found to be associated with PD through investigating genetic polymorphisms or via the whole genome association studies suggest that such genes could also contribute to an increased risk of PD in the general population. Some environmental factors have been found to be associated with genetic factors in at-risk patients, further implicating the role of gene-environment interactions in sporadic PD. There may be confusion for clinicians facing rapid progresses of genetic understanding in PD. After a brief review of PD genetics, we will discuss the insight of new genetic discoveries to clinicians, the implications of ethnic differences in PD genetics and the role of genetic testing for general clinicians managing PD patients.

Autonomic Dysfunctions in Parkinsonian Disorders

Background and Purpose: Symptoms of autonomic dysfunctions are common in the patients with parkinsonian disorders. Because clinical features of autonomic dysfunctions are diverse, the comprehensive evaluation is essential for the appropriate management. For the appreciation of autonomic dysfunctions and the identification of differences, patients with degenerative parkinsonisms are evaluated using structured questionnaire for autonomic dysfunction (ADQ). Methods: Total 259 patients, including 192 patients with [idiopathic Parkinson’s disease (IPD, age 64.6 ± 9.6 years)], 37 with [multiple system atrophy (MSA, 62.8 ± 9.1)], 9 with [dementia with Lewy body (DLB, 73.9 ± 4.3)], and 21 with [progressive supranuclear palsy (PSP, 69.4 ± 9.6)]. The ADQ was structured for evaluation of the presence of symptoms and its severity due to autonomic dysfunction, covering gastrointestinal, urinary, sexual, cardiovascular and thermoregulatory domains. Patients were also evaluated for the orthostatic hypotension. Results: Although dementia with Lewy body (DLB) patients were oldest and duration of disease was longest in IPD, total ADQ scores of MSA and PSP (23.9 ± 12.6 and 21.1 ± 7.8) were significantly increased than that of IPD (15.1 ± 10.6). Urinary and cardiovascular symptom scores of MSA and gastrointestinal symptom score of PSP were significantly worse than those of IPD. The ratio of patient with orthostatic hypotension in IPD was 31.2% and not differed between groups (35.1% in MSA, 33.3% in DLB and 33.3% in PSP). But the systolic blood pressure dropped drastically after standing in patients with MSA and DLB than in patients with IPD and PSP. Conclusions: Patients with degenerative parkinsonism showed widespread symptoms of autonomic dysfunctions. The severity of those symptoms in patients with PSP were comparing to that of MSA patients and worse than that of IPD.

Development of the Korean Version of the Sleep Apnea Quality of Life Index

Objectives Obstructive sleep apnea (OSA) is a disorder characterized by repetitive partial or complete occlusion of the upper airway during sleep that affects quality of life. The aim of this study was to develop the Korean version of the sleep apnea quality of life index (K-SAQLI) and apply it in Korean patients with OSA. Methods Ninety-three patients with OSA completed the K-SAQLI. Its construct validity and responsiveness were tested by comparing the baseline and change scores obtained in each domain (i.e., daily functioning, social interactions, emotional functioning, and symptoms) using the medical outcome survey-short form 36 (SF-36). Results The Cronbach α coefficients of internal reliability exceeded 0.60 in all the domains (daily functioning, 0.89; social interactions, 0.88; emotional functioning, 0.92; symptoms, 0.67; and total, 0.94). The K-SAQLI had a high test-retest correlation coefficient of 0.73 in the 20 randomized selected patients. The construct validity was confirmed by significant correlations with SF-36 subscale scores. Conclusion The results of this study demonstrate that the K-SAQLI may be applicable for clinical purposes.