Ji Seon Kim

Inhibition of inducible nitric oxide synthase expression and cell death by (−)-epigallocatechin-3-gallate, a green tea catechin, in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease

The aim of this study was to investigate the involvement of inducible nitric oxide synthase (iNOS) in the action of (-)-epigallocatechin-3-gallate (EGCG), a potential neuroprotective agent against Parkinsons disease (PD), and to test for toxicity resulting from high doses of EGCG. EGCG was administered to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mice at two different doses (10mg/kg and 50mg/kg). EGCG treatment reduced the neuronal death rate to less than 50%. The level of iNOS expression in the MPTP group was 20% higher than that seen in the control group, but in the EGCG groups, iNOS expression was reduced to the level observed in the negative control group. The two doses of EGCG were equally beneficial for cell rescue, and no toxicity was observed with the higher dose. Inhibition of iNOS may be an important mechanism underlying the prevention of MPTP toxicity, and EGCG may potentially be a neuroprotective agent against PD.

Loss of Nigral Hyperintensity on 3 Tesla MRI of Parkinsonism: Comparison With 123I‐FP‐CIT SPECT

The aim of this study was to investigate whether 3 Tesla susceptibility‐weighted imaging can detect the alteration of substantia nigra hyperintensity in Parkinsons disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) and to assess the concordance between the loss of nigral hyperintensity on 3 Tesla susceptibility‐weighted imaging and the nigrostriatal dopaminergic degeneration indicated by 123I‐2β‐carbomethoxy‐3β‐(4‐iodophenyl)‐N‐(3‐fluoropropyl)‐nortropane single photon emission computerized tomography.

Dopaminergic neuronal integrity in parkinsonism associated with liver cirrhosis.

OBJECTIVE To investigate the nature of parkinsonism associated with liver cirrhosis, which entails examination of the integrity of the nigrostriatal dopaminergic system. METHODS Consecutive patients who had concurrent liver cirrhosis and parkinsonism were investigated with MRI and dopamine transporter (DAT) single-photon emission computerized tomography (SPECT) using iodine I 123 [(123)I]-radiolabeled fluoropropyl (FP) 2-carbomethoxy-3-(4-iodophenyl) tropane (CIT). RESULTS Five patients with liver cirrhosis were identified and confirmed to have concurrent parkinsonism. In all patients, MRI showed increased T1 signals, affecting basal ganglia bilaterally. DAT density was normal in four patients, and these patients had relatively non-progressive, levodopa-unresponsive parkinsonism. In one patient, striatal [(123)I]FP-CIT uptake was reduced, similar to the pattern of idiopathic Parkinsons disease (PD). This patient showed sustained response to levodopa treatment. CONCLUSIONS Our patients showed two different patterns of clinical and neuroradiological features, that is, atypical parkinsonism with normal DAT density, which is clearly differentiated from PD versus levodopa-responsive parkinsonism with reduced DAT density (classical PD). Further investigations using other markers of dopaminergic transmission and histopathological studies should be conducted to elucidate whether damage to the nigrostriatal dopaminergic system occurs in parkinsonism associated with liver cirrhosis.

Relative contribution of SCA2, SCA3 and SCA17 in Korean patients with parkinsonism and ataxia

We examined the relative significance of SCA2, SCA3 and SCA17 in Koreans patients with parkinsonism and ataxia. We recruited patients with either parkinsonism (n = 524; PD = 386 and MSA = 138) or ataxia (n = 44) as their main clinical feature for two years. These patients were screened for SCA2, SCA3 and SCA17. Six cases carried SCA2; one, SCA3; and eight, SCA17. In SCA2 patients, one patient exhibited MSA-P phenotype, and the other five exhibited ataxia. The single patient with SCA3 showed ataxia. In SCA17 patients, one patient presented ataxia, the other seven patients showed parkinsonism (three PD and four MSA-P). Dopamine transporter (DAT) imaging was performed in a subset of ataxic or parkinsonian SCA2 or SCA17, all of whom showed decreased DAT binding. In Korean population, the mutation frequencies of SCA2 and SCA17 were similar. SCA2 was a more significant cause of ataxia, whereas SCA17 was a more significant cause of parkinsonism. Contribution of SCA3 to parkinsonism was insignificant.

SNPs in axon guidance pathway genes and susceptibility for Parkinson's disease in the Korean population

Single-nucleotide polymorphisms (SNPs) in genes of the axon guidance pathway have been reported to be a possible susceptibility factor for Parkinson’s disease (PD). This study investigated whether the genetic variability in the axon guidance pathway is a susceptibility factor in PD patients in the Korean population. A total of 373 patients and 384 healthy subjects were included. A set of 22 SNPs was analyzed, and the risk of PD was evaluated using odds ratios in an unconditional and conditional logistic regression models of age- and gender-matched subsets. A multidimensionality reduction (MDR) analysis was performed to explore potential gene–gene interactions. SNPs in the DCC, CHP, RRAS2 and EPHB1 genes of the axon guidance pathway showed significant associations with PD. The DCC rs17468382 and EPHB1 rs2030737 SNPs may be associated with increased PD risk, and the CHP rs6492998 and RRAS2 rs2970332 SNPs may be associated with reduced PD risk. However, no significant interactions for PD risk were found in the MDR analysis and logistic regression analysis using SNP interaction terms. This study supports that only four of the selected 22 SNPs are regulating factors associated with PD in the Korean population. However, no interactions were found among the SNPs, suggesting that the effect for the pathway as a whole is not greater than that for single genes in the Korean population. Further investigations involving populations of various ethnicities and other genetic markers and models are warranted.

Ceftiaxone-Induced Neurotoxicity: Case Report, Pharmacokinetic Considerations, and Literature Review

Ceftriaxone is widely used in patients for the treatment of serious gram-negative infections. Ceftriaxone can induce some potential side effects, including neurotoxicity, however, nonconvulsive status epilepticus has rarely been reported. We report a case of acute reversible neurotoxicity associated with ceftriaxone. A 65-yr-old woman with chronic kidney disease developed altered consciousness during ceftriaxone treatment for urinary tract infection. The electroencephalogram demonstrated continuous bursts of generalized, high-voltage, 1 to 2 Hz sharp wave activity. Neurologic symptoms disappeared following withdrawal of ceftriaxone. The possibility of ceftriaxone-induced neurotoxicity should be considered in patients developing neurological impairment during ceftriaxone use, and the discontinuation of the drug could lead to complete neurological improvement.

Hyperspectral fluorescence imaging for cellular iron mapping in the in vitro model of Parkinson’s disease

Abstract. Parkinson’s disease (PD) is characterized by progressive dopaminergic cell loss in the substantia nigra (SN) and elevated iron levels demonstrated by autopsy. Direct visualization of iron with live imaging techniques has not yet been successful. The aim of this study is to visualize and quantify the distribution of cellular iron using an intrinsic iron hyperspectral fluorescence signal. The 1-methyl-4-phenylpyridinium (MPP+)-induced cellular model of PD was established in SHSY5Y cells exposed to iron with ferric ammonium citrate (FAC, 100 μM). The hyperspectral fluorescence signal of iron was examined using a high-resolution dark-field optical microscope system with signal absorption for the visible/near infrared spectral range. The 6-h group showed heavy cellular iron deposition compared with the 1-h group. The cellular iron was dispersed in a small particulate form, whereas the extracellular iron was aggregated. In addition, iron particles were found to be concentrated on the cell membrane/edge of shrunken cells. The iron accumulation readily occurred in MPP+-induced cells, which is consistent with previous studies demonstrating elevated iron levels in the SN. This direct iron imaging could be applied to analyze the physiological role of iron, and its application might be expanded to various neurological disorders involving metals, such as copper, manganese, or zinc.

Study of the prevalence of Parkinson's disease using dopamine transporter imaging

Abstract Introduction: To investigate the prevalence of Parkinsons disease (PD), a three-phase study was conducted. Methods: In phase 1, standardized interviews were performed in a random sample of elderly aged 65 years or older using a questionnaire. In phase 2, neurological examinations were performed to clinically diagnose PD. In phase 3, dopamine transporter (DAT) imaging was performed to support the clinical diagnosis. After the three-phase study, longitudinal clinical observation was performed. Results: A total of 714 subjects participated in the phase-1. Two hundred and twenty-two subjects, scored more than two points, were referred to the movement disorder specialist. Eighteen of these subjects showed overt or equivocal Parkinsonian features. Three subjects were clinically diagnosed with possible PD: five with essential tremor with equivocal extrapyramidal signs, eight with frontal-subcortical gait disorder and two with drug-induced Parkinsonism. The three subjects with possible PD showed a typical PD pattern of reduced DAT density. DAT density was normal in the other 15 subjects. Results of long-term follow-up supported the diagnoses. The crude prevalence of PD was 0·42 per 100 persons. Conclusion: During the clinical evaluation, we encountered a very large proportion of subjects with equivocal Parkinsonian features, who posed a diagnostic challenge and a substantial risk of misestimating the prevalence of PD. The combination of DAT imaging and longitudinal clinical observation of equivocal cases enabled us to differentiate PD from other conditions. We suspect that the variation in estimates of the prevalence of PD may be attributable to a considerable proportion of subjects with equivocal Parkinsonian features and how they are evaluated.

Recurrent optic neuritis and neuromyelitis optica-IgG following first and second human papillomavirus vaccinations

Human papillomavirus (HPV) vaccine is widely used to prevent cervical cancer caused by certain types of HPV in girls and young women. Demyelinating disorders within months following HPV innoculation have been reported, but the causal link between HPV vaccination and the onset of demyelinating disorders have not been certain. We report a case of neuromyelitis optica spectrum disorder (NMOSD) that was noteworthy because optic neuritis (ON) occurred in a very close temporal association with both the first and second HPV vaccinations, which might suggest an association between HPV vaccination and the development of NMO-IgG and recurrent ON. This emphasizes the necessity for continuing surveillance for adverse events after HPV vaccination.

Unusual Case of Cerebral Venous Thrombosis in Patient with Crohn's Disease

The development of cerebral venous thrombosis (CVT) as a secondary complication of Crohns disease (CD) seems to be rare, but it is generally accepted that the disease activity of CD contributes to the establishment of a hypercoagulable state. Here, we describe a case of CVT that developed outside the active phase of CD. A 17-year-old male visited the emergency room because of a sudden onset of right-sided weakness and right-sided hypesthesia. He had been diagnosed with CD 1 year before and was on a maintenance regimen of mesalazine and azathioprine. He did not exhibit any symptoms indicating a CD flare-up (bloody stools, abdominal pain, complications, or weight loss). A brain MRI scan revealed an acute infarction of the left frontal cortex and a cortical subarachnoid hemorrhage. Additionally, a magnetic resonance venography revealed a segmental filling defect in the superior sagittal sinus and also the non-visualizability of some bilateral cortical veins. The characteristics of the present case suggest that the risk of CVT is most likely related to CD per se rather than disease activity associated with CD.