Teaching Case

A 32-year-old female was admitted to the Radiology Department by her neurologist with bilateral hearing loss, reduced visual acuity and brainstem and cerebellar dysfunction [ataxia]. Family history was unremarkable. The patient underwent brain MRI and the findings are presented.

The patient had a history of generalized epileptic seizure at the age of 18 for which she had started treatment with Phenobarbital. Three years later she presented reduced acoustic acuity which resulted in bilateral hearing loss. At the same time reduced visual acuity has occurred which was aggravated the following years.
She also suffered from anorexia, incapability of mastication, loss of weight, intense ataxia, myoclonias, psychomotor regression and clinical depression.
Blood and CSF concentration of lactate and red fibers was normal.
Brain MRI showed on T2WI and FLAIR images bilateral hyperintensity of the caudate nuclei, the putamina, the dorsal part of the optic thalami, the periventricular white matter and the semioval centres. There was also a region of hypointensity at the globus pallidi and the posterior limp of the internal capsule. T1WI demonstrated hyperintensity at the caudate nuclei, putamina, globus pallidi and the dorsal parts of the thalami. On T2 STAR images the prementioned areas were hypointense. On the post contrast T1WI there was no enhancement of the lesions. The lesions were bilateral and symmetric.

Leigh’s disease is a rare neurodegenerative disorder of childhood that was first described by Leigh in 1951. It is a subacute necrotizing encephalomyelopathy affecting the gray matter. The metabolic defects are heterogeneous that each causes an impairment in mitochondrial function and hence a chronic energy deprivation syndrome.
About half of the cases show an autosomal inheritance. The other half show X- linked mutations of the E1 subunit puruvate dehydrogenase comlex, maternal mitochondrial DNA point mutations or sporadic inheritance of mitochondrial DNA deletions.
Histopathologic lesions consist of spongiform degeneration, capillary proliferation, and gliosis. The regions affected more are the basal gagglia, the brainstem, the thalami and the dental nuclei. Rarely the lesions are localized at the white matter and the cortex. Characteristically there is bilateral involvement of the putamina and the periaquaductal gray matter.
The disease is most frequently noticed in the first two years of life but rare late onset and adult onset cases are recognized. Clinically, it is characterized by psychomotor retardation, feeding difficulties, hypotonia or weakness and ataxia. Dystonias, tremor, chorea and myoclonus are frequent findings. Disturbance of respiration and abnormal eye movement with or without optic atrophy are common. Death occurs within a few years (usually 1 year) after the onset of symptoms. Acute fulminating illness and prolonged survival have both been reported before.
Most common imaging findings are on NECT the hypodensity of the lesions which do not enhance after contrast administration. On T2WI and FLAIR images the lesions are hyperintense and on T1WI are usually hypointense. On DWI there is restricted diffusion in acute phase and after the contrast administration on T1WI the enhancement is uncommon. On MRS there is usually an increase of choline, a decrease of NAA and lactate is usually positive.
In our case the onset of symptoms was at the age of 18, which is rare as long as the disease is usually noticed until the age of two. Also the findings on T1WI were uncommon considering the affected areas were hyperintense, because of the deposition of degradation products of blood or myelin. The diagnosis of Leigh’s syndrome was established because clinical presentation as well as imaging findings supported the diagnosis. MEERF syndrome, which may have similar presentation, was not confirmed because DNA analysis was negative and lactate concentration was normal in blood and CSF.