Case 36-2005: A Woman with Seizure, Disturbed Gait, and Altered Mental Status
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《新英格兰医药杂志》
To the Editor: In the discussion of the clinical syndromes of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (the MELAS syndrome), Dickerson et al. (Nov. 24 issue)1 do not mention L-arginine therapy. This option should be considered in the treatment of patients with stroke-like episodes. Although no randomized trial of L-arginine therapy for the MELAS syndrome has been performed, observational data support its use, particularly in the acute phase of the disorder.2,3 Improvement has been reported in stroke-like symptoms within 24 hours after the use of this therapy. Improvements in both blood chemistry and magnetic resonance spectroscopy have also been reported.3,4 In our experience, a child with the MELAS syndrome who received daily treatment over a six-month period with L-arginine (at a dose of 0.5 mg per kilogram of body weight) had a reduced frequency of major stroke-like attacks.
We believe that L-arginine therapy should be considered as a treatment option for all patients with the MELAS syndrome.
Tarekegn Geberhiwot, M.D., Ph.D.
Anupam Chakrapani, M.D.
Chris Hendriksz, M.B.Ch.B.
Birmingham Children's Hospital
Birmingham B4 6NH, United Kingdom
References
Case Records of the Massachusetts General Hospital (Case 36-2005). N Engl J Med 2005;353:2271-2280.
Koga Y, Akita Y, Nishioka J, et al. L-arginine improves the symptoms of strokelike episodes in MELAS. Neurology 2005;64:710-712.
Kubota M, Sakakihara Y, Mori M, Yamagata T, Momoi-Yoshida M. Beneficial effect of L-arginine for stroke-like episode in MELAS. Brain Dev 2004;26:481-483.
Koga Y, Ishibashi M, Ueki I, et al. Effects of L-arginine on the acute phase of strokes in three patients with MELAS. Neurology 2002;58:827-828.
The discussants reply: Geberhiwot et al. point out recent experience with the use of L-arginine in the treatment of an acute stroke-like episode or as prophylaxis in the long-term care of patients with the MELAS syndrome. They acknowledge that no systematic trial of the use of L-arginine in the MELAS syndrome or other mitochondrial encephalopathies has been published. The stroke-like episodes in the MELAS syndrome are variable in their frequency, severity, rate and degree of recovery, and recurrence. Improvements in the results of blood chemistry tests and brain chemistry as seen by magnetic resonance spectroscopy are expected during the recovery from an acute episode.
We agree that L-arginine may be considered as a treatment option for the MELAS syndrome. The rationale for its use is that arginine is a substrate for synthesis of nitric oxide, a vasodilator, and for creatine, which is important in the regulation of oxidative phosphorylation in the brain.1,2 Before its use is sanctioned, evaluation of the potential risks and benefits of L-arginine therapy should be performed in a prospective, blinded study and include both clinical outcome measures and noninvasive metabolic imaging of the brain.
David Holtzman, M.D., Ph.D.
Bradford C. Dickerson, M.D.
Massachusetts General Hospital
Boston, MA 02114
References
Braissant O, Gotoh T, Loup M, Mori M, Bachmann C. L-arginine uptake, the citrulline-NO cycle and arginase II in the rat brain: an in situ hybridization study. Brain Res Mol Brain Res 1999;70:231-241.
Hemmer W, Wallimann T. Functional aspects of creatine kinase in brain. Dev Neurosci 1993;15:249-260.
We believe that L-arginine therapy should be considered as a treatment option for all patients with the MELAS syndrome.
Tarekegn Geberhiwot, M.D., Ph.D.
Anupam Chakrapani, M.D.
Chris Hendriksz, M.B.Ch.B.
Birmingham Children's Hospital
Birmingham B4 6NH, United Kingdom
References
Case Records of the Massachusetts General Hospital (Case 36-2005). N Engl J Med 2005;353:2271-2280.
Koga Y, Akita Y, Nishioka J, et al. L-arginine improves the symptoms of strokelike episodes in MELAS. Neurology 2005;64:710-712.
Kubota M, Sakakihara Y, Mori M, Yamagata T, Momoi-Yoshida M. Beneficial effect of L-arginine for stroke-like episode in MELAS. Brain Dev 2004;26:481-483.
Koga Y, Ishibashi M, Ueki I, et al. Effects of L-arginine on the acute phase of strokes in three patients with MELAS. Neurology 2002;58:827-828.
The discussants reply: Geberhiwot et al. point out recent experience with the use of L-arginine in the treatment of an acute stroke-like episode or as prophylaxis in the long-term care of patients with the MELAS syndrome. They acknowledge that no systematic trial of the use of L-arginine in the MELAS syndrome or other mitochondrial encephalopathies has been published. The stroke-like episodes in the MELAS syndrome are variable in their frequency, severity, rate and degree of recovery, and recurrence. Improvements in the results of blood chemistry tests and brain chemistry as seen by magnetic resonance spectroscopy are expected during the recovery from an acute episode.
We agree that L-arginine may be considered as a treatment option for the MELAS syndrome. The rationale for its use is that arginine is a substrate for synthesis of nitric oxide, a vasodilator, and for creatine, which is important in the regulation of oxidative phosphorylation in the brain.1,2 Before its use is sanctioned, evaluation of the potential risks and benefits of L-arginine therapy should be performed in a prospective, blinded study and include both clinical outcome measures and noninvasive metabolic imaging of the brain.
David Holtzman, M.D., Ph.D.
Bradford C. Dickerson, M.D.
Massachusetts General Hospital
Boston, MA 02114
References
Braissant O, Gotoh T, Loup M, Mori M, Bachmann C. L-arginine uptake, the citrulline-NO cycle and arginase II in the rat brain: an in situ hybridization study. Brain Res Mol Brain Res 1999;70:231-241.
Hemmer W, Wallimann T. Functional aspects of creatine kinase in brain. Dev Neurosci 1993;15:249-260.