Ho-Sung Ryu

Alpha-synuclein in gastric and colonic mucosa in Parkinson's disease: Limited role as a biomarker

Gastric and colonic alpha‐synuclein immunoreactivity has been reported in patients with Parkinsons disease (PD). However, enteric alpha‐synuclein also has been reported in healthy individuals.

Clinical Heterogeneity of Atypical Pantothenate Kinase-Associated Neurodegeneration in Koreans

Objective Neurodegeneration with brain iron accumulation (NBIA) represents a group of inherited movement disorders characterized by iron accumulation in the basal ganglia. Recent advances have included the identification of new causative genes and highlighted the wide phenotypic variation between and within the specific NBIA subtypes. This study aimed to investigate the current status of NBIA in Korea. Methods We collected genetically confirmed NBIA patients from twelve nationwide referral hospitals and from a review of the literature. We conducted a study to describe the phenotypic and genotypic characteristics of Korean adults with atypical pantothenate kinase-associated neurodegeneration (PKAN). Results Four subtypes of NBIA including PKAN (n = 30), PLA2G6-related neurodegeneration (n = 2), beta-propeller protein-associated neurodegeneration (n = 1), and aceruloplasminemia (n = 1) have been identified in the Korean population. The clinical features of fifteen adults with atypical PKAN included early focal limb dystonia, parkinsonism-predominant feature, oromandibular dystonia, and isolated freezing of gait (FOG). Patients with a higher age of onset tended to present with parkinsonism and FOG. The p.R440P and p.D378G mutations are two major mutations that represent approximately 50% of the mutated alleles. Although there were no specific genotype-phenotype correlations, most patients carrying the p.D378G mutation had a late-onset, atypical form of PKAN. Conclusions We found considerable phenotypic heterogeneity in Korean adults with atypical PKAN. The age of onset may influence the presentation of extrapyramidal symptoms.

Mortality of advanced Parkinson's disease patients treated with deep brain stimulation surgery

OBJECTIVE Despite the widespread use of deep brain stimulation (DBS) for patients with Parkinsons disease (PD), long-term outcomes remain unclear. We aimed to analyze the mortality of advanced PD patients who received DBS surgery. METHODS We assessed the survival rate of 158 consecutive advanced PD patients who underwent DBS surgery between April 2002 and May 2014. Kaplan-Meier survival curves were constructed using death as the endpoint. Cox proportional hazards regression models were used to assess the association of clinical risk factors with survival. RESULTS Twenty-seven (17.1%) PD patients (13 men and 14 women) died during the mean follow-up period of 5.3±3.1years. The survival rate was 97% at 3years and 85% at 5years after DBS surgery. Pneumonia (n=7) was the most common specific cause of death. Orthostatic hypotension was more frequent in deceased patients than in survivors (P=0.026). In a step-wise Cox regression analysis, male sex (hazard ratio (HR) = 2.58; 95% confidence interval (CI) = 1.19–5.60; P = 0.016), visual hallucination (HR = 9.53; 95% CI = 3.50–26.01; P < 0.001), and nursing home admission (HR = 6.76; 95% CI = 2.40–18.99; P < 0.001) predicted poor survival. CONCLUSION The poor survival of advanced PD patients who underwent DBS surgery was associated with male sex, orthostatic hypotension, visual hallucination, and nursing home admission.

Psychiatric symptoms in myoclonus-dystonia syndrome are just concomitant features regardless of the SGCE gene mutation

INTRODUCTION Among myoclonus-dystonia syndrome (MD) patients, psychiatric disorders including depression, anxiety, alcohol dependence, obsessive-compulsive disorder (OCD) and panic disorder have been frequently reported to be related with the epsilon-sarcoglycan gene (SGCE) mutation. However, the rate of psychiatric disorders has not been compared between MD patients with the SGCE mutation (SGCE (+)) and without the SGCE mutation (SGCE (-)). We analyzed the psychiatric data in both SGCE (+) and SGCE (-) MD patients to determine the association of the SGCE mutation with psychiatric disorders in MD. METHODS Twenty-six MD patients who fulfilled the Grunewalds criteria and underwent a SGCE gene study were enrolled. Patients were divided into two groups according to their SGCE status (SGCE (+) and SGCE (-) group). They were systematically assessed using a standardized protocol including motor severity scales and psychiatric questionnaires for depression, anxiety, alcohol dependence, OCD and panic disorder. RESULTS Fifteen SGCE (+) and eleven SGCE (-) patients were enrolled. Mean age at onset, disease duration, family history, alcohol responsiveness and motor severity were not different between the SGCE (+) and SGCE (-) group. Although more than half (53.8%) of all the MD patients had psychiatric symptoms, there were no significant differences between the SGCE (+) and SGCE (-) group in terms of their psychiatric questionnaire scores and rate of psychiatric disorders. CONCLUSIONS Psychiatric features are not likely to be related with the SGCE mutation itself but just bespeak disability in clinical MD syndrome regardless of the SGCE mutation.

Sensory Tricks for Cervical Levodopa-induced Dyskinesia in Patients with Parkinson's Disease

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Infection related to deep brain stimulation in patients with Parkinson disease: Clinical characteristics and risk factors

OBJECTIVE Risk factors of infection after deep brain stimulation (DBS) surgery in patients with Parkinson disease (PD) have been controversial. We aimed to investigate the clinical characteristics and risk factors of infection after DBS surgery in PD patients. METHODS We retrospectively investigated 246 consecutive DBS surgeries in 169 advanced PD patients. Clinical data were collected and analyzed to clarify the clinical characteristics associated with infection after DBS surgery. Multivariate logistic regression analysis was used to assess risk factors for infection after DBS surgery. RESULTS Infection occurred in 5% of all DBS surgeries and in 7% of all PD patients who received DBS surgery. Most infections (75%) occurred within 3months after DBS surgery but it also occurred 21months after DBS surgery. Gram-positive bacteria were the most common pathogens (75%). Infection after DBS surgery was associated with short period of prophylactic antibiotic therapy (OR=0.62, 95% CI=0.45-0.85, P=0.002) and intensive care unit (ICU) management immediate after DBS surgery (OR=5.43, 95% CI=1.12-26.45, P=0.036). CONCLUSION Our study suggests that short period of prophylactic antibiotic therapy and ICU management after surgery may increase the risk of infection in PD patients who received DBS surgery.

Oculodentodigital Dysplasia Presenting as Spastic Paraparesis: The First Genetically Confirmed Korean Case and a Literature Review.

Oculodentodigital dysplasia (ODDD) is a rare autosomal dominant inherited disease caused by mutations of the human gap junction alpha 1 gene, which encodes the protein Connexin-43. Patients with ODDD may present with neurological deficits with a typical pleiotropic combination of characteristic craniofacial, ophthalmological, phalangeal, and dental anomalies. In this report, we describe the first genetically confirmed Korean ODDD patient, who presented with spastic paraparesis. We will also review the neurological aspects of ODDD as reported in the literature.

Association of metals with the risk and clinical characteristics of Parkinson's disease

INTRODUCTION While metals have been implicated in the pathophysiology of Parkinsons disease (PD), the clinical evidence is scarce. Further, the contribution of metals for the risk or clinical presentation of PD remains to be explored. METHODS To investigate the associations between the level of metals in blood serum and PD risk or clinical presentation, including sex-related differences, we studied 325 PD patients and age- and sex-matched 304 controls. We collected clinical data of the PD patients, including age at onset, PD duration, levodopa-equivalent dose (LED), Hoehn and Yahr stage (H-Y stage), presence of motor fluctuation, levodopa-induced dyskinesia (LID), freezing of gait, hallucination, and Mini-Mental State Examination (MMSE) score. Iron, copper, and zinc levels in serum were assayed by inductively coupled plasma mass spectrometry. Statistical analyses were performed to determine the sex-related differences in metal levels. RESULTS Among the three metal elements tested, serum copper levels showed significant correlations with PD risk or clinical presentation. Higher copper levels were associated with a decreased PD risk. Higher copper or lower iron levels were associated with the risk of LID in women. Serum copper levels were negatively correlated with MMSE scores in PD patients. CONCLUSIONS This clinical study suggests significant associations between serum metal levels and PD risk or essential clinical features, demonstrating the possible roles of metals in PD pathogenesis or symptom development.

Association of SNCA variants with α-synuclein of gastric and colonic mucosa in Parkinson's disease

BACKGROUND Alpha-synuclein (α-Syn) immunostaining in the enteric nervous system (ENS) has been investigated to determine the role of diagnostic biomarker of Parkinsons disease (PD). However, determining factors for alpha-synuclein (α-Syn) deposition in the ENS of humans are still unclear. We aimed to investigate a possible association between SNCA variants and the presence of α-Syn immunostaining in the ENS in patients with PD and healthy individuals. METHODS The study subjects consisted of 38 patients with PD and 46 healthy individuals. α-Syn immunohistochemistry was performed for gastric and colonic mucosal tissues of patients with PD and controls. Mucosal biopsy tissues of the ENS were obtained using standard biopsy forceps by endoscopic gastroduodenoscopy or colonoscopy. Two variants within the SNCA gene (the single nucleotide polymorphism [SNP] rs11931074 and the microsatellite REP1) were genotyped. RESULTS In patients with PD, the rs11931074 (G allele) was significantly associated with the presence of α-Syn immunostaining in the ENS (OR = 5.96, 95% CI = 1.70-20.97, P = 0.01). In an interaction analysis, SNP rs11931074-PD status interaction was significantly associated with positive α-Syn immunostaining in the ENS (OR = 7.33, 95% CI = 1.58-33.88, P = 0.01). Longer SNCA REP1 alleles were not associated with positive α-Syn immunostaining in the ENS. CONCLUSION This exploratory study demonstrated that α-Syn deposition in the ENS may be associated with SNCA variants in patients with PD.

Relation of Enteric α-Synuclein to Gastrointestinal Dysfunction in Patients With Parkinson's Disease and in Neurologically Intact Subjects

Background/Aims α-Synucleinopathy in the brain is the neuropathological hallmark of Parkinson’s disease (PD). However, the functional impact of α-synucleinopathy in the enteric nervous system remains unknown. We aim to evaluate the association between gastrointestinal (GI) dysfunction and α-synuclein (αSYN) pathology in the stomach and colon of PD patients and controls, as well as to investigate the association between the αSYN pathology in GI tract and future PD risk. Methods A total of 35 PD patients and 52 neurologically intact subjects were enrolled in this study. Endoscopic biopsies were performed, and then immunohistochemical staining for αSYN was performed. All subjects completed the validated Rome III questionnaire for the assessment of GI symptoms. The association between GI symptoms and the αSYN pathology in GI mucosa was evaluated. Incident PD cases were assessed during a median follow-up of 46 months. Results The proportion of self-reported constipation and functional constipation through the Rome III questionnaire was significantly higher in PD patients than in controls (P < 0.001 and P = 0.015). However, no significant association was found between the αSYN pathology in the stomach and colon mucosa and constipation, as well as other GI symptoms including dyspepsia symptoms and abdominal discomfort or pain, regardless of the presence or absence of clinical PD (P > 0.05). No incident PD cases were diagnosed during study period. Conclusions Our present study suggests that the deposition of αSYN in the mucosal enteric nervous system may not be reflected by functional impairment of the affected segment of the gut.