Won Tae Yoon

Prevalence of multiple sclerosis in Korea

Objective: The aim of this study was to estimate the prevalence of multiple sclerosis (MS) in Korea through a nationwide survey. Methods: We estimated the prevalence of MS in Korea using several sources collected between 2000 and 2005: verified cases from 38 major referral hospitals across the nation, the National Health Insurance (NHI) payment request data from NHI Corporation of Korea, and the national mortality dataset from Statistics Korea. We established a network of neurologists from 38 major referral hospitals and performed a nationwide hospital survey for MS cases. The diagnoses of MS were validated according to the McDonald criteria. The diagnostic validity of each hospital was evaluated from hospital survey data to reduce the uncertainty of NHI data and was applied to estimate the prevalence using novel statistical methods. Results: The estimated numbers of MS cases in Korea through 2 different statistical methods which adjust NHI data by the diagnostic validity of each hospital were very similar: 1,681 (95% confidence interval [CI] 1,490–1,902) by the stratification method and 1,640 (95% CI 1,402–1,789) by the linear regression method. The crude MS prevalence was 3.5–3.6 cases per 100,000 individuals. The estimated female-to-male ratio was 1.26. Conclusion: This study is the first nationwide survey for the prevalence of MS in Korea utilizing a national database in complementary way. We found an increase in the prevalence of MS that is consistent with reports from neighboring Asian countries.

Restless legs syndrome in Korean patients with drug-naïve Parkinson's disease: A nation-wide study

BACKGROUNDnRestless legs syndrome is a common neurologic disorder, and there is increasing evidence for a dopaminergic link between Parkinsons disease and restless legs syndrome. However, most previous studies did not take into account the effects of dopaminergic medication. We conducted a nation-wide, cross-sectional study to determine the prevalence and clinical characteristics of restless legs syndrome in Korean drug-naïve Parkinsons disease patients.nnnMETHODSnOne hundred and fifty-one drug-naïve patients with Parkinsons disease were enrolled from 18 centers in South Korea over the course of one year. Clinical profiles of parkinsonism, restless legs syndrome, psychiatric symptoms, and laboratory data were collected. The findings of subjects with and without restless legs syndrome were compared.nnnRESULTSnThe prevalence of restless legs syndrome in drug-naïve patients with Parkinsons disease was 16.5%. Subjects with restless legs syndrome had a higher mean Hoehn and Yahr stage and more severe limb parkinsonism, especially tremor. There was, however, no difference in iron metabolism between patients with and without restless legs syndrome. Analysis demonstrated that Becks depression inventory score was associated with the severity of restless legs syndrome.nnnCONCLUSIONnOur study demonstrated an increased prevalence of restless leg syndrome in drug-naïve patients with Parkinsons disease than in the general population. Based on the association between parkinsonism and restless legs syndrome, and the unique characteristics of restless legs syndrome in patients with Parkinsons disease, we suggest that the pathophysiology of restless legs syndrome in Parkinsons disease differs from that in patients without Parkinsons disease.

Increased Pulsatility Index Is Associated with Intracranial Arterial Calcification

Background/Aims: An increase in the pulsatility index (PI) has been suggested to reflect distal vascular resistance. The purpose of the present study was to investigate the association between intracranial arterial calcification and intracranial PIs. Methods: Consecutive patients with acute ischemic stroke or transient ischemic attack were included. The PIs of both middle cerebral arteries (MCAs) were measured by transcranial Doppler ultrasonography. Intracranial carotid artery calcification (ICAC) was assessed on computed tomography angiography, and then compared with the mean PI of both MCAs. Patients with internal carotid artery steno-occlusion were excluded from this study. Results: A total of 156 patients were finally enrolled. The prevalence of diabetes increased as the PI value increased (p for trends; p = 0.025). PI was correlated with ICAC score (r = 0.413, p < 0.001) and age (r = 0.507, p < 0.001). Multiple linear regression analysis indicated that aging and ICAC were independent determinants of the PI of MCA after adjusting for sex, systolic blood pressure, smoking, and the presence of diabetes. Conclusions: This study shows that an increase in PI was correlated with the severity of ICAC, which suggests calcification-related vascular resistance might have a role in the elevation of PI.

IL-1β Induction and IL-6 Suppression Are Associated with Aggravated Neuronal Damage in a Lipopolysaccharide-Pretreated Kainic Acid-Induced Rat Pup Seizure Model

Objectives: Reportedly, hippocampal neuronal degeneration by kainic acid (KA)-induced seizures in rats <14 days old was enhanced by lipopolysaccharide (LPS). This study was to test the hypothesis that cytokines such as interleukin (IL)-1β, IL-6 and tumor necrosis factor-α are associated with aggravated neuronal damage. Materials and Methods: Sixty male Sprague-Dawley, 14-day-old rats were used. Experiments were conducted in saline, LPS + saline, saline + KA and LPS + KA groups. Intraperitoneal LPS injections (0.04 mg/kg) were administered 3 h prior to KA injection (3 mg/kg). Results: The LPS + KA group showed a tendency toward shorter latency to seizure onset (p = 0.086) and significantly longer seizure duration (p < 0.05) compared with the KA group. Induction of the proconvulsant cytokine IL-1β in rat pup brains was significantly greater in the LPS + KA group compared to the KA group (38.8 ± 5.5 vs. 9.2 ± 1.0 pg/µg; p < 0.05); however, IL-6 levels were higher in the KA group than in the LPS + KA group (108.7 ± 6.8 vs. 60.9 ± 4.7 pg/µg; p < 0.05). The difference in tumor necrosis factor-α between the LPS + KA group and the KA group was insignificant (12.1 ± 0.6 vs. 10.9 ± 2.3 pg/µg; p = 0.64). Conclusions: Our results showed an increase in the proconvulsant cytokine IL-1β and a decrease in a potentially neuroprotective cytokine, IL-6, in rat pups treated with LPS + KA. These results warrant further investigation into the possible role of IL-1β induction and IL-6 suppression in LPS-promoted neuronal damage.

Post-interventional microembolism: cortical border zone is a preferential site for ischemia.

Background: Previous diffusion-weighted MRI (DWI) studies have indicated that 10–40% of patients have silent embolism during neurointerventional procedures. However, lesion patterns of the embolisms have not been adequately investigated. Methods: DWI was taken within 7 days before and 48 h after cerebral angioplasty and stent procedures. New lesions on the follow-up DWI were analyzed in the non-treated arterial territories. Based on the arterial territories, supratentorial lesions were classified into cortical lesions and subcortical lesions. Cortical lesions were subdivided into cortical border zone and cortical proper lesions. Subcortical lesions were divided into deep perforator and internal border zone lesions. Infratentorial lesions were divided into brainstem and cerebellar lesions. Results: 72 patients were included in this study. There were 223 new DWI lesions (1–23 lesions) in the non-treated arterial territories of 37 patients. There were 154 cortical lesions, 45 cerebellar lesions, 21 subcortical lesions and 3 brainstem lesions. Analysis of the distribution pattern of cortical lesions showed that 88 of 154 lesions were located at the cortical border zone. Of the subcortical lesions, 13 of 21 lesions were located at the internal border zone area, within the corona radiata and centrum ovale. Only 4 lesions were located at the deep perforator territory. Infratentorial lesions were mostly located at the cerebellar hemisphere (45/48). Most lesions were tiny infarcts (<5 mm diameter); 7 of 223 lesions were >10 mm in diameter. Conclusions: Interventional-angiography-related microembolisms mostly lodge in the cerebral cortical border zone area and cerebellar hemisphere. Microembolisms to the deep perforating artery territory are distinctly rare.

Small Deep Infarction in Patients with Atrial Fibrillation: Evidence of Lacunar Pathogenesis

Background: It is difficult to clarify whether small deep infarction is caused by cardioembolism or intrinsic small vessel disease in patients with atrial fibrillation (AF). The purpose of this study was to determine whether preexisting small vessel disease would differ according to the presenting infarct pattern and to determine the factors associated with acute single small deep infarction in stroke patients with AF. Methods: Between January 2008 and August 2012, 1,592 consecutive patients with acute ischemic stroke presenting within 7 days of symptom onset were entered in a prospectively maintained stroke registry. For the present study, 231 stroke patients with AF were enrolled irrespective of the stroke subtype. We divided these patients into 2 groups (lacunar infarct pattern, n = 20, vs. nonlacunar infarct pattern, n = 211) according to the acute infarct pattern on diffusion-weighted imaging. Patients with acute single small deep infarction on diffusion-weighted imaging were assigned to the lacunar infarct pattern group. We assessed the severity of preexisting small vessel disease by grading white matter lesions (WMLs) according to the Fazekas scale (periventricular WML score ranging from 0 to 3 and deep WML score ranging from 0 to 3 were added to give a total WML score ranging from 0 to 6), multilacunar state (number of chronic lacunes ≥2) and the presence of microbleeds. Demographic characteristics, vascular risk factors and neuroimaging data were compared between the two groups. Results: Patients with a lacunar infarct pattern showed more severe WMLs than those with a nonlacunar pattern [median total WML score 2.5 (range 2-4) vs. 1.0 (0-2); p < 0.001]. A multilacunar state was more prevalent in the lacunar infarct pattern group compared with the nonlacunar pattern group (65 vs. 28.9%; p = 0.001). However, the presence of microbleeds did not differ between the groups. Multiple logistic regression analyses revealed periventricular WMLs [odds ratio (OR) 4.12, 95% confidence interval (CI) 2.14-7.92], deep WMLs (OR 3.42, 95% CI 1.75-6.66) and multilacunar state (OR 7.85, 95% CI 2.45-25.6) as the predictors of a lacunar infarct pattern. Conclusions: The severity of WMLs and chronic lacunes were independent predictors of the incident infarct pattern, which suggested that acute single small deep infarction might be caused by intrinsic small vessel disease despite the presence of concomitant AF.

Association between Pulse Wave Velocity and Nerve Conduction Study in Diabetic Patients

Background/Aims: Brachial-ankle pulse wave velocity (baPWV) is a marker of vascular stiffness and is reported to be associated with diabetic neuropathy; however, the relationship between baPWV and nerve conduction study (NCS) has yet to be examined. Methods: Between January 2006 and December 2008, we investigated this relationship in diabetic patients. To this end, we reviewed the medical records of 100 diabetic patients for whom both baPWV and NCS had been examined. Results: The mean age of patients was 55.4 ± 10.6 years, and the mean duration of diabetes mellitus was 6.3 ± 7.3 years. A statistically significant inverse correlation between baPWV and NCS was observed, especially in the lower extremity sensory NCS [superficial peroneal sensory nerve action potential (SNAP), r = –0.466, p <0.05; sural SNAP, r = –0.384, p <0.01]. A multiple linear regression analysis also demonstrated a significant association between baPWV and some parameters of NCS (SNAP of sural nerve, and nerve conduction velocity of peroneal and sural nerves). Conclusion: These results indicate that the degree of systemic arterial stiffness is associated with peripheral nerve status in diabetic patients, but it is unclear what this signifies and further study is needed.

The Usefulness of Proximal Radial Motor Conduction in Acute Compressive Radial Neuropathy

Background and Purpose The objective of this study was to determine diagnostic and prognostic values of proximal radial motor conduction in acute compressive radial neuropathy. Methods Thirty-nine consecutive cases of acute compressive radial neuropathy with radial conduction studies-including stimulation at Erbs point-performed within 14 days from clinical onset were reviewed. The radial conduction data of 39 control subjects were used as reference data. Results Thirty-one men and eight women (age, 45.2±12.7 years, mean±SD) were enrolled. All 33 patients in whom clinical follow-up data were available experienced complete recovery, with a recovery time of 46.8±34.3 days. Partial conduction block was found frequently (17 patients) on radial conduction studies. The decrease in the compound muscle action potential area between the arm and Erbs point was an independent predictor for recovery time. Conclusions Proximal radial motor conduction appears to be a useful method for the early detection and prediction of prognosis of acute compressive radial neuropathy.

Is cerebral white matter involvement helpful in the diagnosis of dentatorubral-pallidoluysian atrophy?

Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disease clinically characterized by the presence of cerebellar ataxia in combination with variable neurological symptoms. Cerebral white matter involvement of DRPLA is rare and reported mainly in severe, progressed cases of old-aged or juvenile-onset DRPLA. We describe three cases of genetically confirmed DRPLA that developed changes in cerebral white matter in the early stage of middle-aged patients. Our results of our study indicate that cerebral white matter changes are not rare in DRPLA and might be helpful for differentiation in ataxia patients with brainstem and cerebellum atrophy.

Behavioural and trait changes in parkinsonian patients with impulse control disorder after switching from dopamine agonist to levodopa therapy: results of REIN-PD trial

Objective In this multicentre open-label trial, we compared behavioural and neuropsychiatric symptoms in Parkinson’s disease (PD) patients with impulse control disorders (ICD) treated with dopamine agonists before and 12 weeks after substituting dopamine agonists with an equivalent dose of levodopa/carbidopa slow-release formulation. Methods Baseline characteristics of 50 PD patients with ICD were compared with those of 60 medicated and 40 drug-naive PD control groups. Neuropsychiatric trait changes in the PD-ICD group were investigated 12 weeks after the intervention. ICD behaviours were assessed via modified Minnesota Impulsive Disorders Interview (mMIDI), whereas parkinsonian severity and neuropsychiatric characters were systematically assessed with the Unified PD Rating Scale (UPDRS) and a predefined neuropsychological assessment battery. Results At baseline, ICD patients showed higher scores in the Neuropsychiatric Inventory and anxiety, anger and obsessive-compulsive traits compared with both PD control groups. In contrast, the three PD groups showed indifference in the impulsivity scales. At 12 weeks post intervention, ICD behaviours significantly improved (p<0.001, Δ modified MIDI score=‒5.27 ± 5.75) along with the UPDRS II daily activity scores (p=0.02, Δ=‒2.07 ± 4.53). Behavioural disinhibition tended to improve (p=0.06), although no significant changes were observed in the Neuropsychiatric Inventory and personality trait scores. Dopamine agonist withdrawal syndrome developed in 5.3% of the PD-ICD group. Conclusions This study provides class IV evidence suggesting that switching from dopamine agonists to levodopa/carbidopa slow-release formulations alleviated ICD behaviours in PD patients leading to improvement in daily activities whereas neuropsychiatric traits associated with ICD persisted after the 12-week therapy. Trial registration number NCT01683253.