A Genome-Wide Association Study Identifies UTRN Gene Polymorphism for Restless Legs Syndrome in a Korean Population

OBJECTIVE: Restless legs syndrome (RLS) is a highly heritable and common neurological sensorimotor disease disturbing sleep. The objective of study was to investigate significant gene for RLS by performing GWA and replication study in a Korean population. METHODS: We performed a GWA study for RLS symptom group (n=325) and non-RLS group (n=2,603) from the Korea Genome Epidemiology Study. We subsequently performed a replication study in RLS and normal controls (227 RLS and 229 controls) to confirm the present GWA study findings as well as previous GWA study results. RESULTS: In the initial GWA study of RLS, we observed an association of rs11645604 (OR=1.531, p=1.18×10−6) in MPHOSPH6 on chromosome 16q23.3, rs1918752 (OR=0.6582, p=1.93×10−6) and rs9390170 (OR=0.6778, p=7.67×10−6) in UTRN on chromosome 6q24. From the replication samples, we found rs9390170 in UTRN (p=0.036) and rs3923809 and rs9296249 in BTBD9 (p=0.045, p=0.046, respectively) were significantly associated with RLS. Moreover, we found the haplotype polymorphisms of rs9357271, rs3923809, and rs9296249 (overall p=5.69×10−18) in BTBD9 was associated with RLS. CONCLUSION: From our sequential GWA and replication study, we could hypothesize rs9390170 polymorphism in UTRN is a novel genetic marker for susceptibility to RLS. Regarding with utrophin, which is encoded by UTRN, is preferentially expressed in the neuromuscular synapse and myotendinous junctions, we speculate that utrophin is involved in RLS, particularly related to the neuromuscular aspects.

A Case of Severe Obesity-Hypoventilation Syndrome Treated by Bilevel Positive Airway Pressure Therapy

Obesity-Hypoventilation syndrome (OHS) is characterized by morbid obesity, hypoxia, and hypercapnea during wakefulness without parechymal lung disease or severe obstructive sleep apnea. A woman was admitted because of mental deterioration and diagnosed as OHS on the basis of obesity and hypoventilation, while awake, after ruling out other causes. By bilevel positive airway pressure (BiPAP) therapy, hypercapnea and hypoxia were resolved. We report that BiPAP can be an effective treatment for severe hypercapnea and hypoxia in OHS, which obviate the need for invasive endotracheal intubation.

Cerebrovascular Complication in Tuberculous Meningitis

BACKGROUND: Cerebral infarction as a complication of tuberculous meningitis (TBM) is not uncommon, but has been rarely reported. The purposes of this study were to evaluate the clinical characteristics of cerebral infarction secondary to TBM and investigate the predictive values for cerebral infarction in patients with TBM. METHODS: We prospectively collected patients with TBM for 24 months. Patients were divided into two groups, either patients with stroke or without stroke. We compared the demographic features, clinical, laboratory, and neuroradiologic findings between the two groups. We classified the stroke subtype with neuroimaging findings. RESULTS: The 26 patients were diagnosed as TBM, and 6 patients had complications with cerebral infarction. The neutrophil percentage in the cerebrospinal fluid (CSF) leukocyte were significantly higher in patients with stroke than in patients without stroke (p=0.0098). On initial CT scan, meningeal enhancement was found in 9 patients, and 4 of them complicated with stroke. However, there were no significant differences in the other clinical and laboratory features such as demographic features, interval between meningitis onset time and treatment initiation time, peripheral white blood cell count, and CSF findings. In six patients with stroke, lacunar infarctions and non-lacunar territorial infarctions were found in 3 patients, respectively. In territorial non-lacunar infarction patients, one patient died due to herniation. CONCLUSIONS: We suggest that the possibility of cerebral infarction under the treatment of TBM should be considered, when the patient shows focal neurologic signs, meningeal enhancement on the CT scan and sustained polymorphic CSF pleocytosis.

Prevalence of Parkinsonism in Ansan-city

BACKGROUND: The prevalence of neurodegenerative disorders are not well documented in Korea. We assessed the prevalence of Parkinsonism in an elderly population in Ansan-city, which is a newly industrialized community with rural origins. METHODS: Randomly selected individuals were selected from a larger Ansan Cohort Study for this study. The sample in the Ansan cohort represented approximately 1.3% (4, 700) of 362, 625 adults (age >18) in the city registery in 1998. Among this group, 4, 218 subjects (1, 086 subjects, age> 60) agreed to be interviewed and receive physical examination and neuropsychological tests by a neurologist and neuropsychologist. All participants including those who either had bradykinesia and at least one another possible cardinal sign of Parkinsonism at the neurologic screening, those who reported that they had PD, or those who were taking antiparkinsonian drugs were examined. RESULTS: In our study, 16 subjects showed parkinsonism. The prevalence of Parkinsonism in this population was 0.37%. Prevalence increased with age, and the prevalence figures were 1.47% for those aged 60 years and older. Postural instability and gait disturbance type was more common in older age group. The results of the neuropsychological tests were as followings: (1) only 2 subjects showed low scores (< 20) in Korea-version Mini-mental status examination (K-MMSE), (2) 8 subjects showed 0.5 & 2 of clinical dementia rating (CDR) and (3) other 8 subjects showed 0 of CDR. CONCLUSIONS: Age is a risk factor for Parkinsonism. The result of our prevalence study is similar to those studies conducted in western countries.

Prevalence of Parkinsonism in Ansan-city

BACKGROUND: The prevalence of neurodegenerative disorders are not well documented in Korea. We assessed the prevalence of Parkinsonism in an elderly population in Ansan-city, which is a newly industrialized community with rural origins. METHODS: Randomly selected individuals were selected from a larger Ansan Cohort Study for this study. The sample in the Ansan cohort represented approximately 1.3% (4, 700) of 362, 625 adults (age >18) in the city registery in 1998. Among this group, 4, 218 subjects (1, 086 subjects, age> 60) agreed to be interviewed and receive physical examination and neuropsychological tests by a neurologist and neuropsychologist. All participants including those who either had bradykinesia and at least one another possible cardinal sign of Parkinsonism at the neurologic screening, those who reported that they had PD, or those who were taking antiparkinsonian drugs were examined. RESULTS: In our study, 16 subjects showed parkinsonism. The prevalence of Parkinsonism in this population was 0.37%. Prevalence increased with age, and the prevalence figures were 1.47% for those aged 60 years and older. Postural instability and gait disturbance type was more common in older age group. The results of the neuropsychological tests were as followings: (1) only 2 subjects showed low scores (< 20) in Korea-version Mini-mental status examination (K-MMSE), (2) 8 subjects showed 0.5 & 2 of clinical dementia rating (CDR) and (3) other 8 subjects showed 0 of CDR. CONCLUSIONS: Age is a risk factor for Parkinsonism. The result of our prevalence study is similar to those studies conducted in western countries.

The Actions of Sodium Valproate in Headache model Evoked by Substance-P in rats

BACKGROUND AND PURPOSE: Valproic acid (2-propylpentanoic acid) which enhances GABA synthesis and blocks it's degradation has been useful treatment of migraine and may activate GABA receptors to modulate trigeminal nociceptive neurons innervating the meninges. But the mechanism and action of sodium valproate in headache is not clear. To investigate the mechanism of valproic acid action in headache model, we compared the change of dural plasma protein extravasation in both substance-P neurogenic inflammation rats with valproic acid pretreatment and without valproic acid pretreatment. METHOD: Sprague-Dawely rats were pretreated with valproate 30 minutes prior to substance-P administration in order to test the effects of sodium valproate on dural plasma protein extravasation by detecting the amount of extravasated Evans blue in the dura matter. To examine the abilities of either bicuculine (GABAA antagonist) and phaclofen (GABAB antagonist) to reverse the effect of valproate, they were administered 5 min before valproate administration. After then we also test the effect of muscimol (GABAA agonist) and bicuculine (GABAA antagonist) in substance-P induced neurogenic inflammation rats. RESULTS: Intraperitoneal injection of sodium valproate and muscimol reduced dural plasma protein extravasation after intravenous substance-P administration. The GABAA antagonist bicuculine completely reversed the effect of valproate and muscimol on plasma extravasation following substance-P administration, whereas the GABAB receptor antagonist, phaclofen, did not. CONCLUSION: We concluded that the attenuation of dural plasma protein extravasation by valproate and muscimol is mediated by via GABAA receptors within the meninges. Agonists and modulators at the GABAA receptor may become useful for the development of selective therapeutic agents for migraine headache.

A Case of Incontinentia Pigmenti with Destructive Encephalopathy

Becker muscular dystrophy is a X-linked recessive disease with the affected gene at locus Xp21, characterized by progressive muscular weakness. Without the definite family history, it has been known that the diagnosis of this disease is almost impossible on clinical grounds alone. We reviewed the muscle pathology of two casses of genetically confirmed Becker muscular dystrophy to know the diagnositc significances of this study. The first case, a 20 year old man, is the classical one with definite family history of X-linked recessive heredity. The muscle pathology of the biceps showed dystrophic muscular changes, including increased internal nuclei, marked variation of fiber sizes and mild endomysial fibrosis. The dystrophin stain of the muscle was also confirmative for the diagnosis. The second case was a 32 year old man who has been biopsied his left vastus lateralis 5 years before this genetic diagnosis. This case is a sporadic one without the family history. The diagnosis at the time of muscle biopsy was limb-girdle muscular dystorphy or inclusion body myositis because of the typical rimmed vacuoles and marked variation of fiber sizes. The dystophin stain was not available at that time. Our conclusion is that the molecular genetic study and/or dystrophin protein test of muscle biopsy should be done in every clinically suspected patient, including limb-girdle muscular dystorphy, inclusion body myositis or rimmed vacuolar myopathies.

An Autopsy Case of the AIDS Presented with Disseminated Cryptococcosis / 감염

Central nervous system cryptococcosis is common in the AIDS patients with reported incidences ranging from 1.9% to 11.0%. Cryptococcosis may be the initial manifestation of HIV infection or occur simultaneously with other opportunistic infections. HIV-infected patients with central nervous system cryptococcosis complain of fever, headache, nausea and vomiting, and cognitive dysfunction. Meningeal signs and photophobia are less common than in HIV-negative patients. Focal neurologic signs and seizures are uncommon. Disseminated cryptococcosis is often concomitantly found at the time of central nervous system cryptococcosis. We report a case of 49 year-old Korean female with HIV infection who died of disseminated cryptococcosis with autopsy findings.