Neuronal Intranuclear Inclusion Disease with Abnormal Peripheral Nerve Conduction

A 70-year-old female presented with progressive gait disturbance. Neurologic examination revealed sensory impairment, hyporeflexia, and sensory ataxia. Nerve conduction study demonstrated mildly decreased velocity in motor nerves. Brain magnetic resonance imaging showed high signal intensities in the corticomedullary junction on diffusion weighted imaging. Neurocognitive function test implied mild cognitive impairment. Based on eosinophilic intranuclear inclusions in pathology, neuronal intranuclear inclusion disease was confirmed. Neuronal intranuclear inclusion needs to be considered when abnormal nerve conduction studies are consistent with abnormal brain imaging findings.

Therapeutic Effect of Levodopa/Carbidopa/Entacapone on Sleep Disturbance in Patients with Parkinson’s Disease

Objective@#To investigate the efficacy of levodopa/carbidopa/entacapone (LCE) at bedtime for treating sleep disturbance in patients with Parkinson’s disease (PD) with motor fluctuations. @*Methods@#Participants included 128 PD patients with motor fluctuations. All patients were assessed for motor, nonmotor, and sleep-specific symptoms using the United Parkinson’s Disease Rating Scale (UPDRS), the Korean version of the Nonmotor Symptom Scale, the Parkinson’s Disease Sleep Scale (PDSS), the Epworth Sleepiness Scale, and the Rapid Eye Movement Sleep Behavior Disorder Screening Questionnaire (RBDSQ). We compared the baseline characteristics of patients with sleep disturbance (PDSS score < 120) and those without sleep disturbance (PDSS score ≥ 120). Thirty-nine patients with sleep disturbance who agreed to take LCE at bedtime completed 3-month follow-ups. We analyzed changes in the scores of motor, nonmotor, and sleep symptom scales over the 3 months. @*Results@#PD patients with sleep disturbance were at more advanced disease stages and had more severe motor, nonmotor, and sleep symptoms than those without sleep disturbance. Patients who took LCE at night showed improvements in motor (UPDRS part III, p = 0.007) and sleep symptoms (total PDSS, p < 0.001). Sleep features that benefitted from LCE included not only nocturnal motor components but also insomnia (PDSS items 2 and 3, p = 0.005 and p < 0.001) and rapid eye movement behavior disorder (PDSS item 6, p = 0.002; and RBDSQ, p < 0.001). @*Conclusion@#The use of LCE at bedtime may be a useful treatment for sleep disturbance in advanced PD patients with motor fluctuations.

A Case of Idiopathic Infratentorial Superficial Siderosis

Superficial siderosis is attributed to hemosiderin deposition in the subpial layers of the nervous system. The clinical features of infratentorial superficial siderosis (ISS) are hearing loss, cerebellar ataxia, and corticospinal tract signs and the most common cause of idiopathic ISS is a dural defect. As magnetic resonance imaging (MRI) has advanced, the diagnosis of infratentorial superficial siderosis can be confirmed by unique radiological findings in MRI. Here, we report on a female patient diagnosed with idiopathic ISS by means of clinical symptoms and radiological findings.

Axonal Charcot-Marie-Tooth case with a novel heterozygous variant in MFN2 assessed by the MutationDistiller

Charcot-Marie-Tooth (CMT) disease can be divided mainly into demyelination and axonopathy based on the results of the electrophysiological study. Mitofusin 2, encoded by MFN2 gene, has a crucial role in the fusion of mitochondria, which is known to associate with CMT type 2A as one of the axonal forms. We describe a 44-year-old man with progressive weakness on bilateral legs after noticing foot drop in his early teen. When we examined him at 45 years of age, he presented atrophy on entire legs and with distal muscle weakness on limbs. The nerve conduction study revealed severely decreased amplitude on motor nerve ranging from 0.2 to 4.5 mV, while conduction velocity remained more than 30.4 m/s. The whole-exome sequencing revealed a novel variant c.2228G>T in MFN2 by efficient genetic analysis tool, MutationDistiller. This report will not only expand the mutation spectrum of CMT2A but also introduce a time-saving genetic analysis tool.

Axonal Charcot-Marie-Tooth case with a novel heterozygous variant in MFN2 assessed by the MutationDistiller

Charcot-Marie-Tooth (CMT) disease can be divided mainly into demyelination and axonopathy based on the results of the electrophysiological study. Mitofusin 2, encoded by MFN2 gene, has a crucial role in the fusion of mitochondria, which is known to associate with CMT type 2A as one of the axonal forms. We describe a 44-year-old man with progressive weakness on bilateral legs after noticing foot drop in his early teen. When we examined him at 45 years of age, he presented atrophy on entire legs and with distal muscle weakness on limbs. The nerve conduction study revealed severely decreased amplitude on motor nerve ranging from 0.2 to 4.5 mV, while conduction velocity remained more than 30.4 m/s. The whole-exome sequencing revealed a novel variant c.2228G>T in MFN2 by efficient genetic analysis tool, MutationDistiller. This report will not only expand the mutation spectrum of CMT2A but also introduce a time-saving genetic analysis tool.

New Classification of Tremors: 2018 International Parkinson and Movement Disorder Society

Tremor is one of the most common movement disorders. The classification of tremor disorders was originally proposed in 1998, but subsequent advances have highlighted the limitations of the original criteria. A task force on tremor was convened by the International Parkinson and Movement Disorders Society to review the previous criteria and to develop a revised classification scheme that will allow a more-comprehensive phenotype, thereby facilitating the discovery of specific etiologies. In this review we provide an overview of how to classify tremor disorders according to the new classification of tremors.

Fragile X-Associated Tremor/Ataxia Syndrome: An Illustrative Case

No abstract available.

Delayed Anoxic Encephalopathy after Carbon Monoxide Poisoning: Evaluation of Therapeutic Effect by Serial Diffusion-Tensor Magnetic Resonance Imaging and Neurocognitive Test

Delayed anoxic encephalopathy after carbon monoxide (CO) poisoning is characterized by neurological deterioration that occurs after recovery from acute CO intoxication. There has been no established therapy. We report a patient recovered from acute CO intoxication developed various neurological symptoms. After the administration of high dose prednisolone and anticholinesterase inhibitor, the therapeutic effect was remarkable and confirmed by quantitative analysis of diffusion-tensor imaging (DTI). DTI could be used to evaluate the therapeutic effect for delayed anoxic encephalopathy after CO poisoning.

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 0.05). 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.

Hand Tremor Questionnaire: A Useful Screening Tool for Differentiating Patients with Hand Tremor between Parkinson's Disease and Essential Tremor

BACKGROUND AND PURPOSE: Hand tremor is one of the most frequent symptoms in movement disorders, and differential diagnoses for hand tremor include Parkinson's disease (PD) and essential tremor (ET). However, accurately differentiating between PD and ET in clinical practice remains challenging in patients presenting with hand tremor. We investigated whether a questionnaire-based survey could be useful as a screening tool in patients with hand tremor. METHODS: A questionnaire related to hand tremor consisting of 12 items was prospectively applied to patients with PD or ET in three movement-disorder clinics. Each question was analyzed, and a query-based scoring system was evaluated for differentiating hand tremors between PD and ET. RESULTS: This study enrolled 24 patients with PD and 25 patients with ET. Nine of the 12 questions differed significantly between PD and ET: 1 about resting tremor, 4 questions about action tremor, and 4 about asymmetry. A receiver operating characteristics curve analysis revealed that the 9-item questionnaire showed a good discrimination ability, with a sensitivity of 88% and a specificity of 84%. CONCLUSIONS: The developed Hand Tremor Questionnaire might be a good screening tool for hand tremors in patients with PD and ET.

Sleepiness and Depression in Parkinson's Disease Patients Treated with Ropinirole and Levodopa

OBJECTIVE: We aimed to investigate the effect of ropinirole on excessive daytime sleepiness (EDS) and depression in Parkinson’s disease (PD) with a large population. METHODS: We conducted a cross-sectional observational study at nine hospitals in Korea between April 24, 2013, and April 22, 2015. We analyzed the demographic and clinical features, other medical history, history of antiparkinsonian medication within 6 months, Hoehn and Yahr stage (HY stage), Unified Parkinson’s Disease Rating Scale (UPDRS) part II and III, Epworth Sleepiness Scale (ESS), and 30-item Geriatric Depression Scale (GDS-30). RESULTS: Four-hundred-thirteen patients with PD (mean age: 65.2 ± 9.0 years; men: 227 patients) were analyzed. Multivariate logistic regression analysis showed that age at examination, UPDRS II, and GDS-30 were independent risk factors for EDS and that sex, UPDRS II, and ESS were independent risk factors for depression. CONCLUSION: Our large group study did not find any significant associations of ropinirole with EDS and depression in Korean PD patients.

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.

Comparison of Pallidal and Subthalamic Deep Brain Stimulation in Parkinson's Disease: Therapeutic and Adverse Effects

OBJECTIVE: To compare the therapeutic and adverse effects of globus pallidus interna (GPi) and subthalamic nucleus (STN) deep brain stimulation (DBS) for the treatment of advanced Parkinson's disease (PD). METHODS: We retrospectively analyzed the clinical data of patients with PD who underwent GPi (n = 14) or STN (n = 28) DBS surgery between April 2002 and May 2014. The subjects were matched for age at surgery and disease duration. The Unified Parkinson's Disease Rating Scale (UPDRS) scores and levodopa equivalent dose (LED) at baseline and 12 months after surgery were used to assess the therapeutic effects of DBS. Adverse effects were also compared between the two groups. RESULTS: At 12 months, the mean changes in the UPDRS total and part I–IV scores did not differ significantly between the two groups. However, the subscores for gait disturbance/postural instability and dyskinesia were significantly more improved after GPi DBS than those after STN DBS (p = 0.024 and 0.016, respectively). The LED was significantly more reduced in patients after STN DBS than that after GPi DBS (p = 0.004). Serious adverse effects did not differ between the two groups (p = 0.697). CONCLUSION: The patients with PD showed greater improvement in gait disturbance/postural instability and dyskinesia after GPi DBS compared with those after STN DBS, although the patients had a greater reduction in LED after STN DBS. These results may provide useful information for optimal target selection for DBS in PD.

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.

The First Reported Case of West Nile Encephalitis in Korea

West Nile encephalitis was first identified in 1937, but until now, it was never diagnosed in Korea. A 58-yr-old Korean man was admitted with headache and cognitive dysfunction. The patient had been on a business trip in Guinea. Cerebrospinal fluid (CSF) showed pleocytosis. The patient complained of both leg weakness,and arachnoiditis and myelitis were observed on lumbar magnetic resonance imaging (MRI). A specific neutralizing antibody for West Nile virus was positive in serum. After a treatment with interferon-alpha 3mu, follow up CSF findings recovered completely after 3 months later. The first case of West Nile encephalitis in Korea was imported from Guinea, and was cured successfully.

The First Reported Case of West Nile Encephalitis in Korea

West Nile encephalitis was first identified in 1937, but until now, it was never diagnosed in Korea. A 58-yr-old Korean man was admitted with headache and cognitive dysfunction. The patient had been on a business trip in Guinea. Cerebrospinal fluid (CSF) showed pleocytosis. The patient complained of both leg weakness,and arachnoiditis and myelitis were observed on lumbar magnetic resonance imaging (MRI). A specific neutralizing antibody for West Nile virus was positive in serum. After a treatment with interferon-alpha 3mu, follow up CSF findings recovered completely after 3 months later. The first case of West Nile encephalitis in Korea was imported from Guinea, and was cured successfully.

Analysis of trinucleotide repetitive sequences for Korean patients with spinocerebellar ataxia types 8, 12, and 17

PURPOSE: Spinocerebellar ataxias (SCAs) are progressive neurodegenerative disorders with diverse modes of inheritance. There are several subtypes of SCAs. SCA 8, SCA 12, and SCA 17 are the less common forms of SCAs with limited information available on their epidemiological profiles in Korea. The purpose of this study was to investigate the prevalence of SCA8, SCA12, and SCA17 in Korea. MATERIALS AND METHODS: Ninety-six unrelated Korean patients were enrolled and showed normal trinucleotide repeats through polymerase-chain reaction (PCR) for the genes ATXN1, ATXN2, ATXN3, CACNA1A , and ATXN7, which correspond to SCA1, SCA2, SCA3, SCA6, and SCA7, respectively. PCR products from patients were further analyzed by capillary electrophoresis using fluorescence labeled primers for the genes ATXN8OS, PPP2R2B, and TBP, which correspond to SCA8, SCA12, and SCA17. RESULTS: Three patients had 104, 97, and 75 abnormal expanded repeats in the ATXN8OS gene, the causative gene for SCA8. None of the patients exhibited abnormal repeats in SCA12 and SCA17. Normal trinucleotide repeat ranges of the cohort in this study were estimated to be 17-34 copies (average, 24+/-4 copies) for SCA8, 7-18 copies (average, 13+/-3 copies) for SCA12, and 26-43 copies (average, 35+/-2 copies) for SCA17. CONCLUSION: This study demonstrated that SCA8, SCA12, and SCA17 are rare in Korean patients with SCA, and further genetic studies are warranted to enhance the mutation detection rate in the Korean SCA population.

Intracranial Langerhans Cell Histiocytosis Presenting with Dysarthria and Gait Disturbance

Langerhans cell histiocytosis (LCH) is a rare disease of the monocyte-macrophage system involving clonal proliferation of Langerhans cells. Central nervous system (CNS) involvement of LCH occurs in 10-57% of all LCH cases. This disease is known to present in two ways in the CNS: intracranial tumorous lesions or intracranial nontumorous lesions (neurodegeneration). We report here an LCH patient who developed gait disturbance and dysarthria due to neurodegenerative lesions associated with LCH.

The Effect of COX-2 Inhibitor on the Expression of MMP-13 during Early Fracture Healing Phase in Rats

PURPOSE: This study investigated the effect of COX-2 inhibitor on the expression of MMP-13 in the healing process of fracture. MATERIAL AND METHODS: Adult Sprague-Dawley rats were divided into two groups of twenty five rats each. Unilateral femoral shaft fractures were created artificially under displacement in all two groups. COX-2 inhibitor was only given to the experimental group from the postoperative day 1. At 2 weeks after fracture the rats were sacrificed and the callus from each group was used for histologic examination and real time RT-PCR for MMP-13 expression. RESULTS: Histologically, proliferation of osteoblasts and formation of osteoid was less abundant in the experimental group. In real time RT-PCR, the mean expression of MMP-13 is 2.84+/-2.50 in the control group compared with 1.16+/-1.05 in the experimental group. CONCLUSION: In the early stage of fracture healing, COX-2 inhibitor suppress the expression of MMP-13.

A Biomechanical Study of Two Kinds of Tapered Pedicle Screws in Osteoporotic Lumber Spine / 대한정형외과학회잡지

PURPOSE: To compare the pullout strength and insertion torque of proximally tapered screw (PT) with fully tapered screw (FT) and to investigate the correlation between the pullout strength and bone mineral density, morphology of pedicle, and insertion torque of the screw in osteoporotic lumbar spine. MATERIALS AND METHODS: Fifteen osteoporotic lumbar vertebrae from four white human cadavers were used. Bone mineral density, pullout strength and insertion torque were measured by dual energy x-ray absorptiometry, MTS and torque screw driver individually. RESULTS: The FT screw provided greater pullout force and insertion torque than the PT screw in 12 of 15 vertebrae tested (p<0.01). Pullout strength was correlated with insertion torque in PT (r=0.666, P=0.0006) and FT (r=0.464, P=0.19) screws. CONCLUSIONS: Results of this study indicate that the FT screws provide higher pullout strength and insertion torque than PT screws in osteoporotic lumbar spine and suggest that the development of tapered minor diameter may lead to an improved pedicle screw with high pullout strength and insertion torque. Nevertheless, further study is needed to investigate the effect of tapering the minor diameter on the mechanical bending strength of the screw.