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ARTICLES: P. Kaufmann, D. C. Shungu, M. C. Sano, S. Jhung, K. Engelstad, E. Mitsis, X. Mao, S. Shanske, M. Hirano, S. DiMauro, and D. C. De Vivo Cerebral lactic acidosis correlates with neurological impairment in MELAS Neurology 2004; 62: 1297-1302 [Abstract] [Full text] [PDF]

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Reply to Abe

Petra Kaufmann, MD, Dikoma C. Shungu PhD, and Darryl C De Vivo, MD   (6 July 2004)

Cerebral lactic acidosis correlates with neurological impairment in MELAS

Kazuo Abe, 2-2 Yamadaoka, Suita, 565-0871 Osaka, Japan   (6 July 2004)

Reply to Abe 6 July 2004
Petra Kaufmann, MD, Department of Neurology, Columbia University , Dikoma C. Shungu PhD, and Darryl C De Vivo, MD Send Correspondence to journal: Re: Reply to Abe kathy_pieper{at}urmc.rochester.edu Petra Kaufmann, MD, et al.	We thank Dr. Abe for his interest in our article and agree that MRS does suffer from limited spatial resolution, but this limitation does not invalidate our central conclusion, namely that clinical severity correlates with cerebral lactic acidosis in MELAS. Also, multi-voxel MRSI has a 10-fold higher spatial resolution than single-voxel MRSI. [1] MELAS is also a diffuse disease rather than a focal disease. [2] We found that the brain lactate concentrations are essentially normal in the control subjects and in the asymptomatic patients, mildly elevated in the oligosymptomatic patients and very elevated in the fully symptomatic patients. Partial volume effect is less problematic as the cerebral ventricles dilate. The fully symptomatic patients have the largest cerebral ventricles. We proposed that the astrocyte is over-producing lactate and the neuron is under-utilizing lactate in MELAS because of the shift in the oxidation reduction potential due to the primary defect in the respiratory chain. This suggestion confirms the Magistretti hypothesis which proposes that astrocyte-derived lactate is the primary oxidizable substrate for neuronal metabolism. [3,4] A final possibility is a defect in the movement of lactate from brain to blood associated with down-regulation of the monocarboxylic acid transporter. References 1. Duyn JH, Gillen J, Sobering G, van zijl PC, Moonen CT. Multisection proton MR spectroscopic imaging of the brain. Radiology 1993; 188:277-825. 2. Shungu DC, Sano M, Millar WS et al. "Metabolic, Structural and Neuropsychological Deficits in Mitochondrial Encephalopathies Assessed by 1H MRSI, MRI and Neuropsychological Testing.” Proceedings of the Seventh Scientific Meeting of the International Society for Magnetic Resonance in Medicine, May 1999, Philadelphia, PA 1999. 3. Magistretti PJ. Cellular bases of functional brain imaging: insights from neuron-glia metabolic coupling. Brain Research 2000; 886:108-112. 4. De Vivo DC. Cerebral energy failure.Current Neurology and Neuroscience Reports 2001;1:203-204.
Cerebral lactic acidosis correlates with neurological impairment in MELAS 6 July 2004
Kazuo Abe, MD Dept.Neurology, Osaka University Grad. Sch.Med, 2-2 Yamadaoka, Suita, 565-0871 Osaka, Japan Send Correspondence to journal: Re: Cerebral lactic acidosis correlates with neurological impairment in MELAS abe{at}neurol.med.osaka-u.ac.jp Kazuo Abe, et al.	I read with interest the article by Kaufmann et al. [1] who report that high levels of ventricular lactate are associated with more severe neurologic impairment using magnetic resonance spectroscopy (MRS). MRS is a promising technique to evaluate brain metabolism in vivo but has drawbacks. Due to the limitation of the sensitivity, it is difficult to position a region of interest (ROI) in one brain tissue (e.g., gray matter, white matter, or CSF). Previous research using MRS could not independently detect metabolic changes in the gray matter and in the white matter. In Figure 1 in the article [1], ROIs in the "gray matter" seemed to include the white matter and the CSF. In the CSF of MELAS proband, peaks were in the "gray matter" and in the CSF, but in the CSF of MELAS oligosymptomatic, a peak was only in the CSF but not in the "gray matter". However, if the "gray matter" includes the CSF, lactate in the CSF should affect a lactate peak in the "gray matter". Using proton chemical shift imaging (1H-CSI), Kizu et al [2] observed lactate peaks in the lateral ventricles for all patients with normal pressure hydrocephalus (NPH). As Bateman [3] queries in his letter, "Ventricular lactate in normal pressure hydrocephalus: from where has it come to where does it go?". My question is: "Ventricular lactate in MELAS: from where has it come to where does it go?". References 1. Kaufmann P, Shungu DC, Sano MC et al. Cerebral lactic acidosis correlates with neurological impairment in MELAS Neurology 2004; 62: 1297-1302. 2. Kizu O, Yamada K, Nishimura T. Proton chemical shift imaging in normal pressure hydrocephalus. Am J Neuroradiol 2001;22:1659-­1664 3. Bateman GA. Ventricular lactate in normal pressure hydrocephalus: from where has it come to where does it go? Am J Neuroradiol 2001;22:1061-1062.