Defective Brain Energy Metabolism Shown by in vivo³¹P MR Spectroscopy in 28 Patients with Mitochondrial Cytopathies

Abstract

Summary:We studied brain energy metabolism by phos phorus magnetic resonance spectroscopy e1p MRS) in 28 patients with mitochondrial cytopathies, and 20 normal control subjects. Fourteen patients had myopathy alone, six had only mild brain symptoms, and eight showed dif ferent degrees of brain involvement. Brain 31p MRS showed a low phosphocreatine content in all patients, accompanied by a high inorganic phosphate in 14 of 28 patients. The average value of the Pi concentration in the patient group was significantly (p = 0.009) different from the control group. The cytosolic pH was normal. From these data were derived a high concentration of ADP (calMitochondrial cytopathies are a heterogeneous group of diseases thought to be due to inherited disorders of mitochondrial function (Schneck et aI., 1973; Berenberg et aI., 1977; Di Mauro et aI., 1985), and characterized by a wide variety of clinical phe notypes (Schneck et aI., 1973; Berenberg et aI., 1977; Pavlakis et aI., 1984; Di Mauro et aI., 1985; Hurko and McKann, 1985; Bourd et aI., 1987; Frackowiak et aI., 1988;Wallace et at., 1988; Berk ovic et aI., 1989). Many patients show symptoms and signs involving multiple organs as in Kearns Sayre syndrome (KSS), in myoclonic epilepsy and Received July 30, 1992; final revision received December 9, 1992; accepted December 9, 1992.Address correspondence and reprint requests to Prof. B. Barbiroli at Istituto di Clinic a N eurologica, via U. Foscolo 7, 40123 Bologna, Italy.Abbreviations used: CPEO, chronic progressive external oph thalmoplegia; DRESS, depth-resolved surface-coil spectros copy; FID, free induction decay; KSS, Kearns-Sayre syndrome; LHON, Leber's hereditary optic neuropathy; MELAS, mito chondrial encephalomyopathy, lactic acidosis, and stroke-like episodes; MERRF, myoclonic epilepsy and ragged-red fibers; MRS, magnetic resonance spectroscopy; PCr, phosphocreatine; PP, phosphorylation potential. 469culated from the creatine kinase equilibrium), a high per cent value of V/V max for ATP biosynthesis, and a low phosphorylation potential, all features showing a de rangement of brain energy metabolism, in all patients with mitochondrial cytopathies. 31p MRS proved to be sensitive enough to disclose a deficit of mitochondrial functionality not only in the affected patients, but also in those without clinically evident brain symptoms. Key Words: Brain bioenergetics-Impaired brain energy me tabolism-Mitochondrial cytopathies-Brain MR spec troscopy.

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