Leigh syndrome: serial MR imaging and clinical follow-up

Abstract

Background and purpose: Subacute necrotizing encephalomyelopathy, or Leigh syndrome (LS), is a progressive neurodegenerative disorder characterized by symmetrical spongiform lesions in the brain with onset usually in infancy or early childhood. Little is known of the developing process of the brain lesions in LS that are particularly relevant to the occurrence of fatal respiratory failure. Our purpose was to determine whether fatal respiratory failure can be predicted before death on the basis of clinical characteristics or findings on longitudinal MR images of the brain.

Methods: Clinical records and serial MR studies of eight patients with LS aged 3 months to 12 years who met the diagnostic criteria for LS were reviewed retrospectively, with special reference to a correlation between loss of respiratory control and MR abnormalities. Both T1- and T2-weighted images were obtained at the onset of disease or when clinical symptoms worsened.

Results: Serial MR images were divided into three groups on the basis of the following findings: 1) symmetrical basal ganglia lesions before brain stem involvement (n = 4); 2) initial involvement of the brain stem (n = 2); and 3) cerebral white matter lesions followed by brain stem lesions (n = 2). Lesions of the lower brain stem were always present when patients had near fatal respiratory failure. However, upper brain stem lesions were transient and were found in parallel to reversible respiratory disorder. Fatal respiratory failure was unpredictable from clinical or neuroradiologic findings.

Conclusion: Brain stem lesions are associated with the loss of respiratory control in patients with LS, but the time at which fatal respiratory failure will occur is unpredictable.

fig 1.

Patient 1: group BG lesion pattern. Axial T2-weighted image (2000/80/2) at the age of 7 months during an acute strokelike episode shows a hyperintense lesion in the right parietotemporal region (arrowheads)

fig 2.

Patient 2: group BG lesion pattern. A, Axial T2-weighted image (2000/80/2) at the age of 3 years shows increased signal intensity in the bilateral putamina and caudate heads, but no detectable brain stem lesion. Clinical findings included mental retardation, muscle weakness, and failure to thrive. B and C, Axial (B) and sagittal (C) T2-weighted images (2000/80/2) at the age of 9 years show static and atrophic lesions in the bilateral putamina and progressive lesions in the cerebral white matter, corpus callosum, and medial medulla oblongata (arrow, C). Clinical findings included irregular breathing, lethargy, and inability to feed.

fig 3.

Patient 6: group BS lesion pattern. A–C, Axial T2-weighted images (2000/80/2) at the age of 11 months show lesions in the substantia nigra (arrows, B) and periaqueductal region (arrowheads, B), and subtle increased signal intensity within the medullary reticular formation (arrow, C) but not in the basal ganglia. Clinically, the patient had episodic unexplained tachypnea.

fig 4.

Patient 8: group WM lesion pattern. A and B, Coronal (A) and axial (B) T2-weighted images (2000/80/2) at the age of 12 years show symmetrical hyperintensity in the cerebral white matter (arrows, A), thalamus, basal ganglia, and medullary tegmentum (arrowheads, B). Clinically, the patient had acute respiratory failure.

fig 5.

Brain stem lesions on MR images and abnormal respiration. Patient numbers correspond to those in Table 1. L indicates lower brain stem lesion; U, upper brain stem lesion; BG, basal ganglia lesion; WM, cerebral white matter lesion; solid line, duration of the disease; solid circle, acute respiratory failure; dotted line, permanent mechanical ventilation; cross, death