Fig. 1.

Cranial MRI, histochemical and biochemical investigations. MRI of Patient 1 showing bilateral T2 hyperintensities involving supratentorial white matter (yellow arrows), head of caudate nucleus (white arrows), putamen and genu and splenium of the corpus callosum (a) characterised by low T1 signal suggesting irreversible tissue damage (b). MRI of Patient 2 showing extensive T2 hyperintensities associated with volume loss involving bilateral periventricular and central white matter (d, e, yellow arrows) and defects involving both putamina and the head of caudate nucleus on the right (c, d, f, white arrows). Right (R) and left (L) are indicated. (g) Haematoxylin and eosin stain shows normal skeletal muscle morphology. Succinate dehydrogenase (SDH) (h), cytochrome c oxidase (COX) (i) and COX-SDH histochemistry (j) reveal a generalised and widespread COX deficiency. Respiratory chain enzyme activity measurements in skeletal muscle (k) and fibroblasts (l) demonstrate a severe complex IV defect in skeletal muscle and a mild complex I and IV defect in Patient 1 fibroblast cells compared to age-matched controls (red: controls, blue: patient 1)