phosphorylation potential and mitochondrial V/V,, between patients and controls reported are determined solely by the change in calculated [ADP). Furthermore, the calculations of [ADP) and VIV,, assume that the tissue is in a single compartment with respect to oxidative phosphorylation. This assumption is unjustified in the brain (especially in pathological states), as both neurons and glia have active oxidative metabolism which varies regionally and between cell types.
Montreal Neurological Institute Montreal, Quebec, Canada References 1. Eleff SM, Barker PB, Blackband SJ, et al. Phosphorus magnetic
resonance spectroscopy of patients with mitochondrial cytopathies demonstrates decreased levels of brain phosphocreatine. Ann Neurol 1990;27:626-630 2. Luyten PR, Groen JP, Vermeulen JWAH, den Hollander JA. Experimental approaches to image localized human 31P NMR spectroscopy. Magn Reson Med 1989;ll:l-21 3. Matthews PM, Shoubridge EA, Karpati G, et al. In vivo phosphorus magnetic resonance spectroscopy in the evaluation of progressive myoclonus epilepsy with abnormal mitochondria. Neurology (Suppl) 1989;39:257 (Abstr) 4. Berkovic S, Carpenter S, Karpati G, et al. Myoclonus epilepsy and ragged red fibers (MERRF): a clinical, pathological, biochemical, magnetic resonance spectrographic, and positron emission tomographic study with a new hypothesis for the pathogenesis of mitochondrial encephalomyopathies. Brain 1989;112:12311260 5. Bottomley PA, Charles HC, Roemer PB, et al. Human in vivo phosphate metabolite imaging with 31PNMR. Magn Reson Med 1988;7:319-336
mM (mean rfr SD, n = 5) is very close to Bottomley’s most recent value for PCr of 5.18 rfr 0.89 from normal brain [3) but is different from his older data cited by Matthews and Arnold, of 3.2. Matthews and Arnold comment on our choice of MRS technique, possible muscle contamination, and usefulness of [ADP) calculations in our report. We purposely chose a standard surface coil technique available on most clinical scanners 14). This technique does not use a “large static magnetic field gradient.” As stated in our paper, magnetic resonance images confirmed lack of muscle contamination. As to the usefulness of ADP calculations, these depend not only on PCr/ATP but also on pH. We do agree that PCr/ATP is the only directly measured value, which was reflected in the title of the manuscript.
TheJohns Hopkins University School of Medicine Baltimore, M D
References Eleff SM, Barker PB, Blackband SJ, et al. Phosphorus magnetic resonance spectroscopy of patients with mitochondrial cytopathies demonstrates decreased levels of brain phosphocreatine. Ann Neurol 1990;27:626-630 Berkovic S, Carpenter S, Karpati G, et al. Myoclonus epilepsy and ragged red fibers (MERRF): a clinical, pathological, biochemical, magnetic resonance spectrographic, and positron emission tomographic study with a new hypothesis for the pathogenesis of mitochondrial encephalomyopathies. Brain 1989;112:12311260 Bottomley PA, Hardy CJ. Rapid, reliable in vivo assays of human phosphate metabolites by nuclear magnetic resonance. Clin Chem 1989;35:392-395 Welch KMA, Levine SR, DAndrea G, et al. Preliminary observations on brain energy metabolism in migraine studied by in vivo phosphorus 3 1 NMR spectroscopy. Neurology 1989;39: 538-541
Reply Scott M. Eleff, MD, Peter B. Barker, D Phil, Steven J. Blackband, PhD, John C. Chatham, D Phil, R. Nick Bryan, MD, PhD, and Orest Hurko, M D Drs Matthews and Arnold refer to data from certain mitochondrial cytopathy patients in which they apparently observed concentrations of phosphate metabolites, as measured by magnetic resonance spectroscopy (MRS), that were normal. Their patients are thus different from our 5 [I) in which all studies showed abnormalities. As they correctly point out in their letter and in earlier reports [Z), there is considerable heterogeneity in pattern and severity of involvement in mitochondrial cytopathies. Indeed, this variability is a hallmark of mitochondrial diseases and is the reason why we propose that in clinical practice, each patient be considered individually. Another possible source of variance is the regions sampled. Our data were from predominantly gray matter of the frontal lobe; Matthews and Arnold’s data were apparently from different areas of the brain. These sources of variation notwithstanding, it is very interesting that they found certain patients in whom there were abnormalities of glucose and oxygen flux but not of phosphorus metabolites, since the two are thought to be closely coordinated. Absolute quantitation of phosphorus MRS is difficult. However, our control value for phosphocreatine (PCr) of 5.3 rfr 0.96
Sleep-related Focal Motor Seizures in Bilateral Central Macrogyria Giovanni Ambrosetto, MD, and Carlo Albert0 Tassinari, M D We read with interest the paper of Kuzniecky and colleagues [If on bilateral central macrogyria. The epileptic seizures of the 4 reported patients were minor absence episodes, generalized tonic-clonic seizures, atonic drop attacks, and head dropping with or without postictal symptoms. The lack of focal motor seizures was stressed. W e wish to report 2 female patients, aged 20 and 32 years respectively, with bilateral central macrogyria on computed tomography scan and magnetic resonance imaging and sleep-related focal motor seizures involving the lips bilaterally. Both had pseudobulbar palsy with oromotor incoordination, developmental delay, and mild mental retardation. Atonic drop attacks were the predominant epileptic pattern but absence-like seizures and generalized tonic-clonic seizures also occurred. N o focal
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Montreal Neurological Institute Montreal, Quebec, Canada References 1. Eleff SM, Barker PB, Blackband SJ, et al. Phosphorus magnetic
resonance spectroscopy of patients with mitochondrial cytopathies demonstrates decreased levels of brain phosphocreatine. Ann Neurol 1990;27:626-630 2. Luyten PR, Groen JP, Vermeulen JWAH, den Hollander JA. Experimental approaches to image localized human 31P NMR spectroscopy. Magn Reson Med 1989;ll:l-21 3. Matthews PM, Shoubridge EA, Karpati G, et al. In vivo phosphorus magnetic resonance spectroscopy in the evaluation of progressive myoclonus epilepsy with abnormal mitochondria. Neurology (Suppl) 1989;39:257 (Abstr) 4. Berkovic S, Carpenter S, Karpati G, et al. Myoclonus epilepsy and ragged red fibers (MERRF): a clinical, pathological, biochemical, magnetic resonance spectrographic, and positron emission tomographic study with a new hypothesis for the pathogenesis of mitochondrial encephalomyopathies. Brain 1989;112:12311260 5. Bottomley PA, Charles HC, Roemer PB, et al. Human in vivo phosphate metabolite imaging with 31PNMR. Magn Reson Med 1988;7:319-336
mM (mean rfr SD, n = 5) is very close to Bottomley’s most recent value for PCr of 5.18 rfr 0.89 from normal brain [3) but is different from his older data cited by Matthews and Arnold, of 3.2. Matthews and Arnold comment on our choice of MRS technique, possible muscle contamination, and usefulness of [ADP) calculations in our report. We purposely chose a standard surface coil technique available on most clinical scanners 14). This technique does not use a “large static magnetic field gradient.” As stated in our paper, magnetic resonance images confirmed lack of muscle contamination. As to the usefulness of ADP calculations, these depend not only on PCr/ATP but also on pH. We do agree that PCr/ATP is the only directly measured value, which was reflected in the title of the manuscript.
TheJohns Hopkins University School of Medicine Baltimore, M D
References Eleff SM, Barker PB, Blackband SJ, et al. Phosphorus magnetic resonance spectroscopy of patients with mitochondrial cytopathies demonstrates decreased levels of brain phosphocreatine. Ann Neurol 1990;27:626-630 Berkovic S, Carpenter S, Karpati G, et al. Myoclonus epilepsy and ragged red fibers (MERRF): a clinical, pathological, biochemical, magnetic resonance spectrographic, and positron emission tomographic study with a new hypothesis for the pathogenesis of mitochondrial encephalomyopathies. Brain 1989;112:12311260 Bottomley PA, Hardy CJ. Rapid, reliable in vivo assays of human phosphate metabolites by nuclear magnetic resonance. Clin Chem 1989;35:392-395 Welch KMA, Levine SR, DAndrea G, et al. Preliminary observations on brain energy metabolism in migraine studied by in vivo phosphorus 3 1 NMR spectroscopy. Neurology 1989;39: 538-541
Reply Scott M. Eleff, MD, Peter B. Barker, D Phil, Steven J. Blackband, PhD, John C. Chatham, D Phil, R. Nick Bryan, MD, PhD, and Orest Hurko, M D Drs Matthews and Arnold refer to data from certain mitochondrial cytopathy patients in which they apparently observed concentrations of phosphate metabolites, as measured by magnetic resonance spectroscopy (MRS), that were normal. Their patients are thus different from our 5 [I) in which all studies showed abnormalities. As they correctly point out in their letter and in earlier reports [Z), there is considerable heterogeneity in pattern and severity of involvement in mitochondrial cytopathies. Indeed, this variability is a hallmark of mitochondrial diseases and is the reason why we propose that in clinical practice, each patient be considered individually. Another possible source of variance is the regions sampled. Our data were from predominantly gray matter of the frontal lobe; Matthews and Arnold’s data were apparently from different areas of the brain. These sources of variation notwithstanding, it is very interesting that they found certain patients in whom there were abnormalities of glucose and oxygen flux but not of phosphorus metabolites, since the two are thought to be closely coordinated. Absolute quantitation of phosphorus MRS is difficult. However, our control value for phosphocreatine (PCr) of 5.3 rfr 0.96
Sleep-related Focal Motor Seizures in Bilateral Central Macrogyria Giovanni Ambrosetto, MD, and Carlo Albert0 Tassinari, M D We read with interest the paper of Kuzniecky and colleagues [If on bilateral central macrogyria. The epileptic seizures of the 4 reported patients were minor absence episodes, generalized tonic-clonic seizures, atonic drop attacks, and head dropping with or without postictal symptoms. The lack of focal motor seizures was stressed. W e wish to report 2 female patients, aged 20 and 32 years respectively, with bilateral central macrogyria on computed tomography scan and magnetic resonance imaging and sleep-related focal motor seizures involving the lips bilaterally. Both had pseudobulbar palsy with oromotor incoordination, developmental delay, and mild mental retardation. Atonic drop attacks were the predominant epileptic pattern but absence-like seizures and generalized tonic-clonic seizures also occurred. N o focal
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