182 JNS 03569 Journal of the Neurological Sciences, 104 (1991) 182-189 © 1991 Elsevier Science Publishers B.V. 0022-510X/91/$03.50 Muscle mitochondrial DNA deletion and 31p-NMR spectroscopy alterations in a migraine patient N. Bresolin 1, p. Martinelli 2, B. Barbiroli 3, P. Zaniol 4, C. Ausenda l, p. Montagna 2, A. Gallanti 2, G.P. Comi l, G. Scarlato ~ and E. Lugaresi 2 ~Istituto di Clinica Neurologica, Centro Dino Ferrari. Universita' degli Studi di Milano, Milan (Italy), 21stituto di Clinica Neurologica and 3Cattedra di Biologia Molecolare. Facolta' di Medicina e Chirurgia, Universita' degli Studi di Bologna, Bologna (Italy), and 41stituto di Radiologia, Universita" degli Studi di Modena, Modena (Italy) (Received 17 October, 1990) (Revised, received 7 March, 1991) (Accepted 19 March, 1991) Key words: Mitochondrial encephalomyopathy; Migraine; mtDNA deletion; 3~p-NMR spectroscopy; Brain bioenergetics; Muscle energy metabolism Summary A 40-year-old female suffering from recurrent migrainous strokes is reported. She did not show any muscle weakness or wasting. Ragged red and cytochrome c oxidase negative fibers were present in the muscle biopsy. Muscle mitochondrial DNA analysis showed a 5 kb deletion, without a point mutation at nucleotide pair 3243 in the mitochondrial tRNA Leu(UUR) gene. Phosphorus nuclear magnetic resonance spectroscopy of brain and gastrocnemius muscle showed a defective energy metabolism in both organs. An increased inorganic phosphate to phosphocreatine ratio due to a decreased phosphocreatine content was found in the occipital lobes, while an abnormal work-energy cost transfer function and a low rate of phosphocreatine post-exercise recovery were found in the muscle. Introduction Patients with stroke-like episodes related to migraine attacks (migrainous stroke) suffer permanent neurological deficit, most often in the posterior cerebral regions. Migraine-like attacks and stroke-like episodes in the pos- terior cerebral regions are also found in patients with mito- chondrial encephalomyopathies (MELAS syndrome) (Montagna et al. 1988). In this syndrome brain involvement is always present together with muscular signs of deranged mitochondrial function (lactic acidosis, ragged red fibers (RRF) and mitochondrial changes on muscle biopsy). Many such patients had been considered cases of "malig- nant" migraine for years before their mitochondrial defect was discovered (Andermann et al. 1986). In a previous study of 9 patients affected with migraine with prolonged aura (5 with migrainous stroke), we found altered mitochondrial energy metabolism in muscle and platelets (Montagna et al. 1988) and upon 31p-NMR spec- Correspondence to: Nereo Bresolin, MD, Istituto di Clinica Neurologica,Universita'degli Studi, Via F. Sforza35, 20122Milan, Italy. Phone: 0039 2 551 84306; Fax: 0039 2 551 90392. troscopy (3~p-NMR) of muscle and brain (Barbiroli et al. 1990). We describe here the genetic and 31p-NMR studies in one such patient, a 40-year-old woman presenting attacks of headache since the age of 14 without any muscle weakness or increased serum lactate level. In muscle biopsy we found two RRF and scattered cytochrome c oxidase (COX) negative fibers, muscle mitochondrial DNA (mtDNA) analysis showing a clear 5 kb deletion. Materials and methods Case report A 40-year-old woman with a negative family history for neurological disorders had been suffering from recurrent, often premenstrual, attacks of headache since the age of 14. At the age of 29 she experienced a sudden loss of conscious- ness, lasting about one hour, followed by a persistent loss of vision in the right part of her visual field. In the following years she had migrainous attacks once or twice a month, sometimes preceded by blurred vision. On neurological examination there was a right lower quadrantic homon-