X-linked Charcot-Marie-Tooth Patient with a Novel Cys168Arg Missense Mutation in the Connexin32 Gene

X-linked Charcot-Marie-Tooth (CMTX) disease is a clinically heterogeneous hereditary motor and sensory neuropathy. The X-linked inheritance showed an absence of male-to-male transmission and a more severe disease phenotype in affected males compared to that in affected female. A missense mutation, Cys168Arg, was found in connexin 32 gene (Cx32/GJB1) from a patient with CMTX neuropathy. The familial history of this patient also suggested that the disease is X-linked CMT. Thus, we report a CMTX family having the novel Cys168Arg mutation in the Cx32 gene.ope

X-linked Charcot-Marie-Tooth Disease Type 1 Harboring Unusual Electrophysiological Features

Charcot-Marie-Tooth X type 1 (CMTX1) is caused by mutations in the connexin 32 gene (Cx32) on the X chromosome. Electrophysiologically, CMTX1 is usually associated with intermediate slowing of conduction velocities and severe impairments in male patients. In addition, patients with CMTX1 rarely present conduction block and temporal dispersion, which are characteristic findings in acquired demyelinating neuropathy. We report herein, for the first time in Korea, two patients with Cx32 mutations who exhibited unusual electrophysiological findings. Key Words: Charcot-Marie-Tooth disease, Connexin 32 (Cx32), Nerve conduction studyope

Clinical and Genetic Aspects in Twelve Korean Patients with Adrenomyeloneuropathy

PURPOSE: This study was designed to investigate the characteristics of Korean adrenomyeloneuropathy (AMN) patients. MATERIALS AND METHODS: We retrospectively selected 12 Korean AMN patients diagnosed by clinical analysis and increased plasma content of very long chain fatty acids. RESULTS: All 12 patients were men. Patient ages at symptom onset ranged from 18 to 55 years. Family history was positive in two patients. The phenotype distributions consisted of AMN without cerebral involvement in seven patients, AMN with cerebral involvement in two patients, and the spinocerebellar phenotype in three patients. Nerve conduction studies revealed abnormalities in four patients and visual evoked tests revealed abnormalities in three patients. Somatosensory evoked potential tests revealed central conduction defects in all of the tested patients. Spinal MRI showed diffuse cord atrophy or subtle signal changes in all 12 patients. Brain MRI findings were abnormal in six of the nine tested patients. These brain abnormalities reflected the clinical phenotypes. Mutational analysis identified nine different ABCD1 mutations in 10 of 11 tested patients. Among them, nine have been previously reported and shown to be associated with various phenotypes; one was a novel mutation. CONCLUSION: In conclusion, the present study is the first to report on the clinical and mutational spectrum of Korean AMN patients, and confirms various clinical presentations and the usefulness of brain MRI scan.ope

SRAM weak cell detection method and failure analysis

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Comparison between the sympathetic skin response and the cardiovascular autonomic function tests in Parkinson's disease

의학과/석사[한글] 자율신경 중상은 파킨슨병에서 흔히 나타난다고 알려져 있으나, 아직까지 이에 대한 연구들은 주로 심혈관계 자율신경 기능에 대한 것으로써 팔다리의 자율신경 장애에 대한 연구들은 상대적으로 미흡하였다. 연구자는 팔다리의 자율신경 장애를 교감신경 피부반응 검사로 측정하고 기존의 심혈관계 자율신경 검사 결과와 비교 분석하여 파킨슨병에서의 자율신경 장애가 심혈관계통 뿐만 아니라 팔다리에도 있는지, 알아보고자 하였다. 또한 팔다리에서 자율신경 장애가 있을 경우, 파킨슨 증상이 있는 부위와 없는 부위에 차이가 있는지 여부 및 자율신경 장애가 levodopa 치료에 의해 영향을 받는지 규명하고자 하였다. 이를 위하여 교감신경 피부반응 검사와 심혈관계 자율신경 기능검사 - 30 : 15 ratio, E : I ratio, Valsalva ratio, isometric exercise test - 를 37명의 파킨슨병 환자와 나이 및 성비가 비슷한 33명의 대조군에서 시행하였는데, 파킨슨병 환자들은 검사를 시행하기 12시간 전부터 투약을 중지하였다. 교감신경 피부반응은 우측의정중 신경과 후경골 신경을 자극하고 우측 손과 발에서 측정하였는데 어느 한쪽에서도 검출되지 않는 경우를 비정상으로 하였다. 파킨슨병에서의 자율신경 장애 중, 교감신경 피부반응에 이상소견을 보인 예는 전체환자의 59%로서 심혈관계 자율신경 검사상 비정상을 보인 빈도인 32%∼81%의 범위에 속하였다. 파킨슨병에서 심혈관계 자율신경 장애가 심하면 교감신경 피부반응 검사에서도 이상 소견을 보이는 경우가 많았는데, 특히 교감신경기능을 측정하는 등장성 운동검사와 교감신경 피부반응 검사간에 높은 연관성을 보였다. 또한 교감신경 피부반응은 levodopa/benserazide (200mg/50mg) 투여에 의하여 크게 영향을 받지 않았으며, 장애가 한쪽 팔다리에 국한된 Stage I 파킨슨병 환자에서도 중상이 있는 부위와 증상이 없는 부위간에 유의한 차이가 없었다. 따라서, 파킨슨병 환자의 자율신경 장애는 심혈관계통 뿐만 아니라 팔다리에서도 비슷한 빈도로 나타나며, 심혈관계 교감신경 기능검사인 등장성 운동검사와 높은 관련을 보인 점으로 보아 주로 중추신경계 교감신경의 기능 이상에 기인할 가능성이 높은 것으로 추정된다. 또한 증상이 없는 팔다리에서도 교감신경 피부반응에서 이상이 나타난 것으로 보아 교감신경의 장애는 운동장애와는 다른 병리병인에 의해 발생하며 특징적인 운동장애 증상이 나타나기 전에도 발현될 수 있는 것으로 보인다. [영문] Autonomic dysfunction commonly occurs in Parkinson's disease, but the pathogenesis of the autonomic dysregulation remains uncertain. Autonomic functions regulating cardiovascular system have been usually investigated in Parkinson's disease, but those involving extremities are not well demonstrated. To compare autonomic dysfunctions of cardiovascular system with those of extremities, we performed sympathetic skin response(SSR) and cardiovascular autonomic function tests(CAFT) - 30 : 15 ratio, E : I ratio, Valsalva ratio, isometric exercise test(IET - in 37 patients with Parkinson's disease and 33 age- and sex- matched healthy controls. The patients were asked to stop antiparkinaonian medications for at least 12 hours prior to tests. SSR was measured at right hand and foot after the electrical stimulation of right median and posterior tibial nerves. Absent SSR at either one or both extremities and CAFT beyond normal ranges were regarded as abnormal. Abnormal SSR was observed in 57% of patients, while abnormal CAFT were found in the range of 32% ∼81%. Patients with abnormal SSR showed more frequent and severe CAFT abnormalities than the patients with normal SSR. Among the CAFT, IET were correlated well with the SSR. SSR abnormality observed in patients were not altered by single dose of levodopa/benserazide (200mg/50mg). There was no significant differences in the incidence of abnormal SSR between symptomatic and asymptomatic extremities in hemi-parkinsonian patients. The results suggest that Parkinsonian sympathetic dysfunction involving either cardiovascular system or extremities may have the same pathophysiology, which is probably the central nervous system origin, and sympathetic dysfunction may be developed before cardinal motor symptoms of Parkinson's disease.restrictio

1H-MR Spectroscopic and SPECT Findings in a Patient with MELAS Syndrome Confirmed by Molecular Genetic Analysis

An eighteen-year-old girl presented recurrent partial and generalized seizures associated with the T-2 high signal intensities of MR brain imaging. Serum and CSF lactate levels were elevated. Muscle biopsy revealed 'ragged red fiber'. The diagnozed proton MR spectroscopy was performed on a GE 1.5 T SIGNA MRI/MRS system and analyzed by STEAM (Stimulated Echo Acquistition Method). 1H-MR spectrocopy demonstrated elevation of lactate contents and decrease of N-acetyl aspartate contents in the involved area. The Tc99m-ECD SPECT revealed multifocal decrease of perfusion in bilateral parietal, temporal and occipital lobe, especially right temporal and left occipital lobe. These features suggest that the pathology of brain lesions of MELAS syndrome may be sub-necrotic incomplete ischemic changes caused by metabolic derangement.ope

Effects of adrenergic antagonists on sympathetically maintained pain in model rats

의과학사업단/박사[한글]말초의 신경손상은 작열통과 같은 만성적 신경병증성 통증을 유발하곤 한다. 작열통환자 중 많은 경우에 교감신경성통증이 나타나며 이에는 자발성통증과 냉자극유발통증이 포함된다. 이러한 교감신경성 의존도가 있는 통증에 관여하는 아드레날린 수용체에 관해서는 아직 알려지지 않고 있다. 본 연구는 말초신경손상 후 생성되는 자발성통증과 냉자극유발통증을 매개하는데 관여하는 아드레날린 수용체 아형을 밝히고자 실시하였다. 신경병증을 유도하기 위하여 L5와 L6 요척수 신경을 결찰하였다. 수술 후 동물을 실온이나 냉온도(5℃)의 금속판에 올려놓고 각 판으로부터 발을 도피하는 시간을 5분간 측정하여 전자의 경우를 자발성통증 그리고 후자의 경우를 냉자극유발통증을 대변하는 행동으로 간주하였다. 각 통증행동이 어떤 아드레날린 수용체 길항제에 의하여 영향을 받는지는 길항제를 신경결찰 하기 전이나 후에 복강내로 투여해준 군과 신경결찰만 가해준 군을 비교하여 조사하였다. 단일신경섬유 기록법을 이용하여 결찰을 시행한 신경(L5)이나 결찰을 하지 않은 신경(L4) 내의 일차 구심성섬유로부터 신경활동을 기록하고 이들 섬유의 아드레날린에 대한 감수성을 조사하였다. 신경결찰 후 실온이나 냉온도의 금속판으로부터 발의 도피기간은 결찰 전에 비하여 증가하였다. 이러한 증가는 40일간의 조사기간 동안 지속되었으며, 알파 수용체의 길항제인 phentolamine에 의하여 그 증가가 억제되었다. 자발성통증 행동은 알파-1 길항제인 prazosin이나 알파-2 길항제인 yohimbine을 신경결찰 전이나 후에 투여했을 때 부분적으로 억제되었다. 냉자극유발통증 행동은 prazosin에 의하여 억제되었으며 yohimbine에 의해서는 영향을 받지 않았다. L5 척수신경 내 손상 받은 구심성 신경섬유 중 자발성방전을 보이는 Aβ-섬유의 반 정도에서 prazosin이 아니라 yohimbine에 의한 흥분반응을 관찰하였다. 한편 L4 척수신경 내 손상 받지 않은 구심성 신경섬유 중 약 12% 정도는 yohimbine이 아니라 prazosin에 의하여 흥분성 반응을 보였다. 본 연구결과는 말초신경 손상 후 나타나는 자발성통증과 냉자극유발통증이 교감신경성 의존적임을 보여주었고, 자발성통증의 생성에는 Aβ-섬유에서의 알파-2 수용체와 C-섬유에서의 알파-1 수용체 모두가 중요한 역할을 할 것이며 냉자극유발통증의 생성에는 C-섬유의 알파-1 수용체가 주로 관여할 것임을 시사한다. [영문]Peripheral nerve injury often leads to chronic neuropathic pain such as causalgia. A subset of patients with causalgia has a sympathetically maintained pain, which is sometimes spontaneous and is often evoked by cooling stimuli. However, our knowledge on adrenergic receptor types responsible for mediating this type of pain is lacking. The present study was conducted to investigate subtypes of adrenoceptors involved in mediating spontaneous pain and cold-evoked pain that developed following peripheral nerve injury. Neuropathic lesion was performed by a unilateral ligation of L5 and L6 spinal nerves of rats. Behavioral signs of cold-evoked pain and spontaneous pain were examined for 5 minutes by measuring cumulative duration of time that the rat lifted its foot off a metal plate held at cold(5℃) or room temperatures. Whether each pain behavior was affected by antagonists of various subtypes of adrenoceptors, which were administered intraperitoneally before and after the ligation, was investigated. Neuronal activity was recorded from primary afferent fibers in L4 non-ligated or L5 ligated spinal nerves using a single fiber recording technique and adrenergic sensitivity of these fibers was examined. After ligation, duration of foot lifting on the ligated side at both cold and room temperatures increased as compared to the pre-operative period. These increases maintained for the entire 40-day test period and were suppressed by treatment with alpha antagonist phentolamine. Pain behavior at room temperature (spontaneous pain) was partially depressed by either alpha-1 antagonist prazosin or alpha-2 antagonist yohimbine when each drug was treated before or after ligation. Pain behavior at cold temperature (cold-evoked pain) was suppressed by prazosin, but not by yohimbine. Of injured afferent fibers in L5 ligated spinal nerves, about half of Aβ-fibers showing spontaneous discharges were excited by yohimbine, not by prazosin. Of uninjured afferent fibers in L4 non-ligated spinal nerves, about 12% of C-fibers were excited by prazosin, but not by yohimbine. The results suggest that peripheral nerve injury develops spontaneous pain and cold-evoked pain that are sympathetically dependent, and that both alpha-1 receptors expressed in C-fibers and alpha-2 receptors expressed in Aβ-fibers may play a critical role for the generation of spontaneous pain whereas alpha-1 receptors expressed in C-fibers are primarily important for the generation of cold-evoked pain.ope

SRAM Defective Cell Model at Subthreshold Retention Fail

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