Abstract
We used phosphorus magnetic resonance spectroscopy (31P MRS) to investigate in vivo the brain and skeletal muscle energy metabolism of 15 children with migraine with aura in interictal periods. Brain 31P MRS disclosed low phosphocreatine and high inorganic phosphate contents, and high intracellular pH in all patients. Calculated [ADP] and the relative rate of mitochondrial oxidation were higher in the brain of patients than in control subjects, whereas the phosphorylation potential was lower. Brain intracellular free Mg2+ concentration was reduced by 25% in patients. Abnormal skeletal muscle mitochondrial respiration was also disclosed in 7 of 15 patients as shown by the slow rate of phosphocreatine postexercise recovery. The multisystem bioenergetic failure found in patients with juvenile migraine is comparable to that found in adults with different types of migraine.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- MRS:
-
magnetic resonance spectroscopy
- PCr:
-
phosphocreatine
- Pi:
-
inorganic phosphate;
- max:
-
relative rate of mitochondrial ATP production
- FID:
-
free induction decay
- TC:
-
time constant
References
Raskin NH 1988; Migraine: clinical aspects. In: Headache, 2nd Ed. Churchill-Livingstone, New York, 41–51.
Billi B 1962; Migraine in school children. Acta Paediatr 51: suppl 136 1–151.
Abu-Arafeh I, Russel G 1995; Prevalence and clinical features of abdominal migraine compared with those of migraine headache. Arch Dis Child 72: 413–417.
Hockaday J 1988; Definition, clinical features, and diagnosis of childhood migraine. In: Hockaday J (ed) Migraine in Childhood. Butterworth, London, 5–24.
Winner P, Martinez W, Mate L, Bello L 1995; Classification of pediatric migraine: proposed revision to the IHS criteria. Headache 35: 407–410.
Silver K, Anderman F 1993; Alterning Hemiplegia of childhood: a study of 10 patients and results of flunarizine treatment. Neurology 43: 36–41.
Abu-Arafeh I, Russel G 1995; Paroxysmal vertigo as a migraine equivalent in children: a population-based study. Cephalalgia 15: 411–414.
Welch KMA, Levine SR, D'Andrea G, Schultz LR, Helpern JA 1989; Preliminary observations on brain energy metabolism in migraine studied by in vivo phosphorus 31 NMR spectroscopy. Neurology 39: 538–541.
Barbiroli B, Montagna P, Cortelli P, Martinelli T, Sacquegna P, Zaniol P, Lugaresi E 1990; Complicated migraine studied by phosphorus magnetic resonance spectroscopy. Cephalalgia 10: 263–272.
Barbiroli B, Montagna P, Funicello R, Iotti S, Monari L, Pierangeli G, Zaniol P, Lugaresi E 1992; Abnormal brain and muscle energy metabolism shown by 31P magnetic resonance spectroscopy in patients affected by migraine with aura. Neurology 42: 1209–1214.
Sacquegna T, Lodi R, DeCarolis P, Tinuper P, Cortelli P, Zaniol P, Funicello R, Montagna P, Barbiroli B 1992; Brain energy metabolism studied by 31P-MR spectroscopy in a case of migraine with prolonged aura. Acta Neurol Scand 86: 376–380.
Montagna P, Cortelli P, Monari L, Pierangeli G, Parchi P, Lodi R, Iotti S, Frassineti C, Zaniol P, Barbiroli B 199431; 31 P-magnetic resonance spectroscopy in migraine without aura. Neurology 44: 666–669.
Uncini A, Lodi R, DiMuzio A, Silvestri G, Servidei S, Lugaresi A, Iotti S, Zaniol P, Barbiroli B 1995; Abnormal brain and muscle energy metabolism shown by 31P-MRS in familial hemiplegic migraine. J Neurol Sci 129: 214–222.
Lodi R, Kemp G, Montagna P, Pierangeli G, Cortelli P, Iotti S, Radda G, Barbiroli B 1997; Quantitative analysis of skeletal muscle bioenergetics and proton efflux in migraine and cluster headache. J Neurol Sci 146: 73–80.
Sangiorgi S, Mochi M, Riva R, Cortelli P, Monari L, Pierangeli G, Montagna P 1994; Abnormal platelet mitochondrial function in patients affected by migraine with and without aura. Cephalalgia 14: 21–23.
Ramadan NM, Halvorson H, Vande-Linde A, Levine H, Low brain magnesium in migraine. Headache 29: 590–593.
Sarchielli P, Costa G, Firerize C, Morucci P, Abritti G, Galla V 1992; Serum and salivary magnesium levels in migraine and tension-type headaches. Results in a group of adult patients. Cephalalgia 12: 21–27.
Thomas, Tomb E, Thomas E, Faure G 1994; Migraine treatment by oral magnesium intake and correction of the irritation of buccofacial and cervical muscles as a side effect of mandibular imbalance. Magn Res 7: 123–127.
Soriani S, Arnaldi C, DeCarlo L, Arcudi D. Mazzotta D, Battistella PA, Sartori S, Abbasciano V 1995; Serum and red blood cell magnesium levels in juvenile migraine patients. Headache 35: 14–16.
Welch KMA, Ramadan NM 1995; Mitochondria, magnesium and migraine. J Neurol Sci 134: 9–14.
Headache Classification Committee of the International Headache Society 1988; Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia 8: 1–96.
EEC Concerted Research Project 1995; Quality Assessment in in vivo NMR spectroscopy. Results of a concerted Research Project of the European Economic Community (6 papers). Magn Reson Imaging 13: 115–176.
Barbiroli B, Montagna P, Martinelli P, Lodi R, Iotti S, Cortelli P, Funicello R, Zaniol P 1993; Defective brain energy metabolism shown by in vivo31P MR spectroscopy in 28 patients with mitochondrial cytopathies. J Cereb Blood Flow Metab 13: 469–474.
Bottomly PA, Foster TH, Darrow RD 1984; Depth-resolved surface-coil spectroscopy (DRESS) for in vivo1H, 31P, and 13C NMR. J Magn Reson 59: 338–342.
Barbiroli B. Lodi R, Iotti S 1996; Phosphorus MR spectroscopy of human brain. An overview after several years' experience studying some 1,200 patients. In: Podo F. Bovée WMMJ, de Certaines J, Henriksen O, Leach M. Leibfritz D (eds) Eurospin Annual. Istituto Superiore di Sanitá, Rome, 385–396.
Bottomly PA, Hardy CJ 1989; Rapid, reliable in vivo assay of human phosphate metabolites by nuclear magnetic resonance. Clin Chem 59: 392–395.
Degani H, Alger J, Shulman R, Petroff O, Prichard J 1987; 31P magnetization transfer studies of creatine kinase kinetics in living rabbit brain. Magn Reson Med 5: 1–12.
Chance B Willams GR 1955; Respiratory enzymes in oxidative phosphorylation. III. The steady state. J Biol Chem 217: 409–427.
Veech RL, Lawson JWR, Cornell NW, Krebs HA 1979; Cytosolic phosphorylation potential. J Biol Chem 254: 6538–6547.
Nioka S, Chance B, Hilberman M, Subramanian H, Leigh J, Veech R. Forster R 1987; Relationship between intracellular pH and energy metabolism in dog brain as measured by 31P-NMR. J Appl Physiol 62: 2094–2102.
Iotti S, Frassineti C, Alderighi L, Sabatini A, Vacca A, Barbiroli B 1996; In vivo assessment of free magnesium concentration in human brain by 31P-MRS. A new calibration curve based on a mathematical algorithm. NMR Biomed 9: 24–32.
Sabatini A, Vacca A, Gans P 1992; Mathematical algorithms and computer programs for the determination of equilibrium constants from potentiometric and spectrophotometric measurements. Coord Chem Rev 120: 389–405.
Iotti S, Lodi R, Frassineti C, Zaniol P, Barbiroli B 1993; In vivo assessment of mitochondrial functionality in human gastrocnemius muscle by 31P MRS. The role of pH in the evaluation of phosphocreatine and inorganic phosphate recoveries from exercise. NMR Biomed 6: 248–253.
Zaniol P, Serafini M, Ferraresi M, Golinelli R, Bassoli P, Canossi I, Aprilesi GC Barbiroli B 1992; Muscle 31P-MR spectroscopy performed routinely in a clinical environment by a whole-body imager/spectrometer. Phys Med 8: 87–91.
Kemp GJ, Taylor DJ, Radda GK 1993; Control of phosphocreatine resynthesis during recovery from exercise in human skeletal muscle. NMR Biomed 6: 66–72.
Petroff OAC, Prichard JW, Behar KL, Alger JR, Shulman T 1985; Cerebral metabolism in hyper- and hypocarbia: 31P and 1H nuclear magnetic resonance studies. Neurology 35: 1681–1688.
Taylor JS, Vigneron DB, Murphy-Boesch J, Nelson SJ, Kessler HB, Coia L, Curran W, Brown TR 1991; Free magnesium levels in normal human brain and brain tumours: 31P chemical-shift imaging measurements at 1.5 T. Proc Natl Acad Sci USA 88: 6810–6814.
Halvorson HR, Vande-Linde AMQ, Helpern JA, Welch KMA 1992; Assessment of magnesium concentration by 31P NMR in vivo. NMR Biomed 5: 53–58.
Barker PB, Boska MD, Butterworth EJ, Hearshen D, Aurora TK, Norris L, Duyn JH, Mooen CTW, Welch KMA 1995; Phosphorus and proton MR spectroscopic imaging in migraine. 3rd Annual Meeting, Society for Magnetic Resonance, Nice, France, 139
Lawson JWR, Veech RL 1979; Effects of pH and free Mg2+ on the Keq of the creatine kinase reaction and other phosphate hydrolyses and phosphate transfer reactions. J Biol Chem 254: 6528–6537.
Ophoff R, Terwindt G, Vergouwe M, vanEijk R, Oefner P, Hoffman S, Lamerdin J, Mohrenweiser H, Bulman D, Ferrari M, Haan J, Eindhout D, vanOmmen G, Hofker M, Ferrari M. Frants R 1996; Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNLIA4. Cell 87: 543–552
May A, Ophoff R, Terwindt G, Urban C, vanEijk R, Haan J, Diener H, Lindhout D, Frants R, Sandkuijl L, Ferrari M 1995; Familial hemiplegic migraine locus on 19p13 is involved in the common forms of migraine with and without aura. Hum Genet 96: 604–608.
Altura B 1985; Calcium antagonist properties of magnesium: implications for antimigraine actions. Magnesium 4: 169–175.
Arnold DL, Matthews PM, Radda GK 1984; Metabolic recovery after exercise and the assessment of mitochondrial function in vivo in human skeletal muscle by means of P-31 NMR. Mag Reson Med 1: 307–315.
Taylor DJ, Bore PJ, Gadian DG, Radda GK 1983; Bioenergetics of intact human muscle. A 31P nuclear magnet resonance study. Mol Biol Med 1: 77–94.
Montagna P, Cortelli P, Barbiroli B 1994; Magnetic resonance spectroscopy studies in migraine. Cephalalgia 14: 184–193.
DiMauro S, Moraes CT 1993; Mitochondrial Encephalomyopathies. Arch Neurol 50: 1197–1208.
Author information
Authors and Affiliations
Additional information
Supported by Telethon-Italy (R.L.).
Rights and permissions
About this article
Cite this article
Lodi, R., Montagna, P., Soriani, S. et al. Deficit of Brain and Skeletal Muscle Bioenergetics and Low Brain Magnesium in Juvenile Migraine: An in Vivo 31P Magnetic Resonance Spectroscopy Interictal Study. Pediatr Res 42, 866–871 (1997). https://doi.org/10.1203/00006450-199712000-00024
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/00006450-199712000-00024
This article is cited by
-
Proteomics profiling reveals mitochondrial damage in the thalamus in a mouse model of chronic migraine
The Journal of Headache and Pain (2023)
-
Defining metabolic migraine with a distinct subgroup of patients with suboptimal inflammatory and metabolic markers
Scientific Reports (2023)
-
Migraine signaling pathways: purine metabolites that regulate migraine and predispose migraineurs to headache
Molecular and Cellular Biochemistry (2023)
-
Mitochondrial function and oxidative stress markers in higher-frequency episodic migraine
Scientific Reports (2021)
-
Structural and Functional Brain Changes in Migraine
Pain and Therapy (2021)