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P4.64 Clinical experience with l -arginine treatment in MELAS syndrome
678
Abstracts / Neuromuscular Disorders 20 (2010) 596–680
1
Hirosaki University of Health and Welfare, Pathology and Medical Neuroscience, Hirosaki, Japan, 2 Hirosaki University School of Medicine, Pediatrics, Hirosaki, Japan, 3 National Aomori Hospital, Pediatrics, Namioka, Japan, 4 National Musashi Center for Neurology and Psychiatry, Tokyo, Japan, 5 National Center for Neurology and Psychiatry, Tokyo, Japan, 6 National Aomori Hospital, Pediatrics, Japan MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) is a maternally inherited multisystem mitochondrial disorder. The common cause of MELAS is a point mutation of mitochondrial DNA. The brain shows various profiles of infarctlike lesions, whose pathogenesis is still unclear, although the involvement of defective mitochondria in neurons and/or in vascular wall cells (mitochondrial angiopathy) is inferred. A 1-year-old boy showed apnea attacks. At age 5, 5.5 and 6, he developed 1st, 2nd and 3rd stroke-like episodes, respectively. His hemiplegia and difficulty of walking and feeding were deteriorated. There were elevations of lactic acid and pyruvic acid levels. Ragged red fibers were demonstrated by muscle biopsy. The mitochondrial DNA analysis revealed a point mutation (A3243G) of tRNALeu (UUR). Presenting hepatic dysfunction and cardiac failure, he died at age 10. The autopsy revealed marked brain atrophy (800 g) and hypertrophic cardiomyopathy (220 g). Microscopically there were many large and small, old and new infarct-like foci in almost all cerebral cortices with accentuation in the occipital lobes. The deep white matter was diffusely atrophied. Infarct-like lesions were also present in the striatum and thalamus. Pseudocalcium deposition was seen in the globus pallidus.In the cerebellum patchy foci of loss of Purkinje cells and granule cells were seen. In the spinal cord degeneration of the posterior and lateral columns was observed. Electron microscopy revealed degeneration of heart muscle cells, choroid plexus epithelial cells, and medial muscle cells and endothelial cells of small vessels with increased accumulation of abnormal mitochondria. The above observations support the hypothesis that energy deficiency due to mitochondrial dysfunction may be responsible for the selective involvement of the most energy requiring tissues such as brain and muscles. doi:10.1016/j.nmd.2010.07.259
P4.64 Clinical experience with L-arginine treatment in MELAS syndrome A. Ishii 1, A. Shioya 1, A. Hosaka 1, N. Ohkoshi 2, K. Nakamagoe 1, A. Tamaoka 1 1 University of Tsukuba, Neurology, Tsukuba, Japan, 2 Tsukuba University of Technology, Neurology, Tsukuba, Japan
Background: Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a rare mitochondrial disorder with a wide range of multisystemic symptoms. Prevention of stroke-like episode is one of the most important strategies for MELAS treatment. It has reported that L-arginine therapy decreased severity of stroke-like symptoms in MELAS. Here we report the clinical experience with intravenous administration of Larginine to the patients associated with acute stroke-like episode. Patients: We administrated intravenous L-arginine therapy to 4 MELAS patients. All were Japanese and diagnosed with MELAS according to clinical findings, ragged-red fibers in muscle biopsy, and A3243G mutation in the mitochondrial tRNALcu(UUR) gene in peripheral lymphocytes. Ages of onset were 9, 13, 46, and 50-year-
old. Two adult-onset patients had deafness and impaired glucose tolerance. Results: Patient 1 was admitted our hospital due to headache, hemianopsia, and convulsion. His first attack was at 9-year-old and he was diagnosed MELAS at 13-year-old. Since 13-year-old he had six stroke-like episodes and took L-arginine therapy. He has no side effects and L-arginine therapy makes his symptoms recover. Patient 2 had admitted our hospital 12 times because of stroke-like episodes and took L-arginine therapy. Although he has mild hemianopsia and fatigue, he is a student in University. Patient 3 was admitted our hospital because of headache and dysarthria. After L-arginine therapy, she developed hypercloremic acidosis. Patient 4 was admitted our hospital because of convulsion and left hand apraxia. After L-arginine therapy, he developed hypercloremic acidosis. Conclusion: Although administration of L-arginine was decreased severity of stroke-like episode in young-onset patients, hyperchloremic metabolic acidosis was occurred in adult-onset patients. The administration of L-arginine to the adult-onset MELAS patients requires careful attention. doi:10.1016/j.nmd.2010.07.260
P4.65 Clinical, pathological and radiological survey of two patients in a Chinese family with Leigh syndrome J. Hu, H.R. Shen The Third Hospital of Hebei Medical University, Neuromuscular Department, Shijiazhuang, Hebei, China We studied the characteristics of clinical, pathological and radiological survey of two patients in a Chinese family with Leigh syndrome. The common clinical characteristic was motor retardation. Two patients had elevated lactate in the blood. One patient had subacute loss of vision in two eyes. The muscle biopsy of two patients showed cytocrome-c oxidase deficiency. Brain magnetic resonance imaging revealed abnormal symmetrical lesions in the Semi-oval center and cerebellar dentate nucleus and revealed increased signal in diffusion-weighted imaging in the parietal white matter, bilaterally and symmetrically not respecting vascular territory or boundaries. Brain magnetic resonance spectroscopy revealed abnormal lactate peak in two patients. In the radiological survey studied, we found that the range of abnormal signal in brain magnetic resonance imaging and diffusion-weighted imaging, when lactate peaks decreased in brain magnetic resonance spectroscopy during improvement of the disease course. The study showed the changes of neuroimaging maybe associated with the course and the state of Leigh syndrome. doi:10.1016/j.nmd.2010.07.261
P4.66 Childhood-onset progressive dystonia associated with m.14459G>A mutation in the mitochondrial DNA: a case report and review of the literature A. Koide 1, H. Ozawa 2, M. Kubota 3, Y. Goto 4 1
Tokyo Metropolitan Children’s Medical Center, Division of Neurology, Tokyo, Japan, 2 Shimada Center for Rehabilitation and Neurodevelopmental Intervention, Department of Regional Medical Support, Tokyo, Japan, 3 National Center for Child Development and Healt, Division of Neurology, Tokyo, Japan, 4 National Institute of Neuroscience, NCNP, Department of Mental Retardation and Birth Defect Research, Tokyo, Japan
Abstracts / Neuromuscular Disorders 20 (2010) 596–680
1
Hirosaki University of Health and Welfare, Pathology and Medical Neuroscience, Hirosaki, Japan, 2 Hirosaki University School of Medicine, Pediatrics, Hirosaki, Japan, 3 National Aomori Hospital, Pediatrics, Namioka, Japan, 4 National Musashi Center for Neurology and Psychiatry, Tokyo, Japan, 5 National Center for Neurology and Psychiatry, Tokyo, Japan, 6 National Aomori Hospital, Pediatrics, Japan MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) is a maternally inherited multisystem mitochondrial disorder. The common cause of MELAS is a point mutation of mitochondrial DNA. The brain shows various profiles of infarctlike lesions, whose pathogenesis is still unclear, although the involvement of defective mitochondria in neurons and/or in vascular wall cells (mitochondrial angiopathy) is inferred. A 1-year-old boy showed apnea attacks. At age 5, 5.5 and 6, he developed 1st, 2nd and 3rd stroke-like episodes, respectively. His hemiplegia and difficulty of walking and feeding were deteriorated. There were elevations of lactic acid and pyruvic acid levels. Ragged red fibers were demonstrated by muscle biopsy. The mitochondrial DNA analysis revealed a point mutation (A3243G) of tRNALeu (UUR). Presenting hepatic dysfunction and cardiac failure, he died at age 10. The autopsy revealed marked brain atrophy (800 g) and hypertrophic cardiomyopathy (220 g). Microscopically there were many large and small, old and new infarct-like foci in almost all cerebral cortices with accentuation in the occipital lobes. The deep white matter was diffusely atrophied. Infarct-like lesions were also present in the striatum and thalamus. Pseudocalcium deposition was seen in the globus pallidus.In the cerebellum patchy foci of loss of Purkinje cells and granule cells were seen. In the spinal cord degeneration of the posterior and lateral columns was observed. Electron microscopy revealed degeneration of heart muscle cells, choroid plexus epithelial cells, and medial muscle cells and endothelial cells of small vessels with increased accumulation of abnormal mitochondria. The above observations support the hypothesis that energy deficiency due to mitochondrial dysfunction may be responsible for the selective involvement of the most energy requiring tissues such as brain and muscles. doi:10.1016/j.nmd.2010.07.259
P4.64 Clinical experience with L-arginine treatment in MELAS syndrome A. Ishii 1, A. Shioya 1, A. Hosaka 1, N. Ohkoshi 2, K. Nakamagoe 1, A. Tamaoka 1 1 University of Tsukuba, Neurology, Tsukuba, Japan, 2 Tsukuba University of Technology, Neurology, Tsukuba, Japan
Background: Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a rare mitochondrial disorder with a wide range of multisystemic symptoms. Prevention of stroke-like episode is one of the most important strategies for MELAS treatment. It has reported that L-arginine therapy decreased severity of stroke-like symptoms in MELAS. Here we report the clinical experience with intravenous administration of Larginine to the patients associated with acute stroke-like episode. Patients: We administrated intravenous L-arginine therapy to 4 MELAS patients. All were Japanese and diagnosed with MELAS according to clinical findings, ragged-red fibers in muscle biopsy, and A3243G mutation in the mitochondrial tRNALcu(UUR) gene in peripheral lymphocytes. Ages of onset were 9, 13, 46, and 50-year-
old. Two adult-onset patients had deafness and impaired glucose tolerance. Results: Patient 1 was admitted our hospital due to headache, hemianopsia, and convulsion. His first attack was at 9-year-old and he was diagnosed MELAS at 13-year-old. Since 13-year-old he had six stroke-like episodes and took L-arginine therapy. He has no side effects and L-arginine therapy makes his symptoms recover. Patient 2 had admitted our hospital 12 times because of stroke-like episodes and took L-arginine therapy. Although he has mild hemianopsia and fatigue, he is a student in University. Patient 3 was admitted our hospital because of headache and dysarthria. After L-arginine therapy, she developed hypercloremic acidosis. Patient 4 was admitted our hospital because of convulsion and left hand apraxia. After L-arginine therapy, he developed hypercloremic acidosis. Conclusion: Although administration of L-arginine was decreased severity of stroke-like episode in young-onset patients, hyperchloremic metabolic acidosis was occurred in adult-onset patients. The administration of L-arginine to the adult-onset MELAS patients requires careful attention. doi:10.1016/j.nmd.2010.07.260
P4.65 Clinical, pathological and radiological survey of two patients in a Chinese family with Leigh syndrome J. Hu, H.R. Shen The Third Hospital of Hebei Medical University, Neuromuscular Department, Shijiazhuang, Hebei, China We studied the characteristics of clinical, pathological and radiological survey of two patients in a Chinese family with Leigh syndrome. The common clinical characteristic was motor retardation. Two patients had elevated lactate in the blood. One patient had subacute loss of vision in two eyes. The muscle biopsy of two patients showed cytocrome-c oxidase deficiency. Brain magnetic resonance imaging revealed abnormal symmetrical lesions in the Semi-oval center and cerebellar dentate nucleus and revealed increased signal in diffusion-weighted imaging in the parietal white matter, bilaterally and symmetrically not respecting vascular territory or boundaries. Brain magnetic resonance spectroscopy revealed abnormal lactate peak in two patients. In the radiological survey studied, we found that the range of abnormal signal in brain magnetic resonance imaging and diffusion-weighted imaging, when lactate peaks decreased in brain magnetic resonance spectroscopy during improvement of the disease course. The study showed the changes of neuroimaging maybe associated with the course and the state of Leigh syndrome. doi:10.1016/j.nmd.2010.07.261
P4.66 Childhood-onset progressive dystonia associated with m.14459G>A mutation in the mitochondrial DNA: a case report and review of the literature A. Koide 1, H. Ozawa 2, M. Kubota 3, Y. Goto 4 1
Tokyo Metropolitan Children’s Medical Center, Division of Neurology, Tokyo, Japan, 2 Shimada Center for Rehabilitation and Neurodevelopmental Intervention, Department of Regional Medical Support, Tokyo, Japan, 3 National Center for Child Development and Healt, Division of Neurology, Tokyo, Japan, 4 National Institute of Neuroscience, NCNP, Department of Mental Retardation and Birth Defect Research, Tokyo, Japan