Dentatorubro-pallidoluysian Atrophy: The Clinical and Molecular Genetic Study of Three Korean Families

Dentatorubro-pallidoluysian atrophy (DRPLA) is a rare neurodegenerative disorder with various clinical phenotypes and has a cytosine-adenine-guanine (CAG) trinucleotide repeat in a gene on chromosome 12. It has been known that trinucleotide repeat disorders show strong inverse correlations between the CAG repeat number and the age of onset and genetic anticipation. The purpose of this study was to investigate whether these observations are applicable to Korean patients. This report involved three Korean families and had on file the history of the 15 affected family mem-bers .Seven of the affected members had the diagnosis of DRPLA which was confirmed by a gene study. We observed inverse correlations between the CAG repeat number and the age of onset and genetic anticipation with high intra- and interfamilial variations. Although our study was in general agreement with previously documented features of DRPLA, some features could not be explained by currently understood pathophysiologic mechanisms.

Anti-oxidative neuroprotection by estrogens in mouse cortical cultures

Estrogen replacement therapy in postmenopausal women may reduce the risk of Alzheimer's disease, possibly by ameliorating neuronal degeneration. In the present study, we examined the neuroprotective spectrum of estrogen against excitotoxicity, oxidative stress, and serum-deprivation-induced apoptosis of neurons in mouse cortical cultures. 17beta-estradiol as well as 17alpha-estradiol and estrone attenuated oxidative neuronal death induced by 24 hr exposure to 100 microM FeCl2, excitotoxic neuronal death induced by 24 hr of exposure to 30 microM N-methyl-D-aspartate (NMDA) and serum-deprivation induced neuronal apoptosis. Furthermore, estradiol attenuated neuronal death induced by Abeta25-35. However, all these neuroprotective effects were mediated by the anti-oxidative action of estrogens. When oxidative stress was blocked by an antioxidant trolox, estrogens did not show any additional protection. Addition of a specific estrogen receptor antagonist ICI182,780 did not reverse the protection offered by estrogens. These findings suggest that high concentrations of estrogen protect against various neuronal injuries mainly by its anti-oxidative effects as previously shown by Behl et al. Our results do not support the view that classical estrogen receptors mediate neuroprotection.

Anti-oxidative neuroprotection by estrogens in mouse cortical cultures

Estrogen replacement therapy in postmenopausal women may reduce the risk of Alzheimer's disease, possibly by ameliorating neuronal degeneration. In the present study, we examined the neuroprotective spectrum of estrogen against excitotoxicity, oxidative stress, and serum-deprivation-induced apoptosis of neurons in mouse cortical cultures. 17beta-estradiol as well as 17alpha-estradiol and estrone attenuated oxidative neuronal death induced by 24 hr exposure to 100 microM FeCl2, excitotoxic neuronal death induced by 24 hr of exposure to 30 microM N-methyl-D-aspartate (NMDA) and serum-deprivation induced neuronal apoptosis. Furthermore, estradiol attenuated neuronal death induced by Abeta25-35. However, all these neuroprotective effects were mediated by the anti-oxidative action of estrogens. When oxidative stress was blocked by an antioxidant trolox, estrogens did not show any additional protection. Addition of a specific estrogen receptor antagonist ICI182,780 did not reverse the protection offered by estrogens. These findings suggest that high concentrations of estrogen protect against various neuronal injuries mainly by its anti-oxidative effects as previously shown by Behl et al. Our results do not support the view that classical estrogen receptors mediate neuroprotection.

Dentatorubropallidoluysian atrophy in a korean family

Dentatorubropallidoluysian atrophy (DRPLA) is a rare neurodegenerative disorder usually inherited with autosomal dominant pattern, which has been mostly described in reports from Japan. Recently, DRPLA proved to be associated with an expanded CAG nucleotide report in a gene on chromosome 12p. We report the first Korean family with this mutation, which was confirmed by genetic analysis. Case History : A 34 year-old man present ad with a 5 year history of clumsiness, seizures, and gait ataxia. He had dysarthria, clumsiness of hands, gait ataxia and intermittent choreic movements in both arms. There was mild cognitive impairment. EEG showed intermittent generalized slowing, and brain MRI revealed diffuse cerebral and cerebellar atrophy with enlarged 4th ventricle. There were three other affected family members; his 37-year old sister presented with choreiform movements developed at the age of 31. His father and uncle were reported to have been ataxic during the late period of their life, who died at age of 65 and 40 respectively. DNA studies of the prebend and his sister confirmed CAG repeat expansiom in the DRPLA gene, the size of which was 64 and 66, respectively. CONCLUSION: This is the first Korean family with DRPLA, and it should be considered in any patients with inherited neurodegenerative disorder with the above-mentioned clinical features

Pure sensory stroke due to brainstem lesion

BACKGROUND & OBJECTIVES: Although thalamic stroke is the most frequent cause of pure sensory stroke, non-thalamic strokes have been also occasionally reported to produce pure sensory stroke(PSS). We attempt to characterize the clinical and radiological features of 11 patients with PSS due to brainstem stroke. SUBJECTS AND METHODS: There were eight men and three women and their age ranged from 50 to 71 years. Their risk factors included hypertension in 10, diabetes mellitus in 2, hyperlipidemia in 3, alcohol drinking in 3 and cigarette smoking in 2. All underwent brain computed tomography(n=11) and/or magnetic resonance imaging(n=8). RESULTS: Five patients presented with pure lemniscal sensory deficits(position and vibration sensation); two presented with abnormalities in all sensory modalities but dominantly involving lemniscal sensation; remaining 4 presented with numbness only. Four patients had cheiro-oral syndrome with bilateral perioral involvement. Imaging studies showed that 6 patients had a small infarct in the paramedian pontine tegmentum, which was thought to be caused by small vessel(lacunar) inclusion. One patient had a small infarct in the lateral part of the midbrain which was probably caused by artery-to-artery embolism originated from mid-basilar stenosis. In addition, four patients had small hypertensive hemorrhage affecting the pontine tegmentum. CONCLUSION: Our result confirms that PSS can be caused by small brainstem stroke of various etiopathology, frequently involving the paramedian pontine tegmentum PSS due to braimtem stroke may be characterized by predom inant lemniscal sensory involvement and occasional bilateral perioral symptoms.