An Atypical Case Presentation of Adult-Onset Leigh's Disease (P07.206)

Abstract

OBJECTIVE: To report a case of an unusual adult-onset presentation of Leigh's disease with autopsy confirmation.

BACKGROUND: Leigh's disease, or subacute necrotizing encephalopathy, is a rare, progressive neurometabolic disorder that results primarily from abnormalities in mitochondrial DNA. Most often, Leigh's disease presents in infants and children. Adult-onset cases are uncommon. Neurological features include movement disorders (e.g. chorea, dystonia, ataxia), hypotonia, spasticity, peripheral neuropathy, ophthalmoplegia, and basal ganglia hyperintensities on magnetic resonance imaging brain scans. Few adult-onset cases have been reported in the literature, and of those, atypical clinical and imaging presentations may be more likely. Thus, these patients may pose diagnostic dilemmas in the clinical setting.

DESIGN/METHODS: A 51-year-old male with no significant family history of movement disorders, was seen in our Movement Disorders clinic for rapidly progressive neurologic abnormalities including ophthalmoparesis, nystagmus, ataxia, and left sided weakness (VIDEO). He developed insomnia, confusion, fluctuating cognition, and hallucinations. Routine blood and cerebrospinal fluid analysis including lactic acid and pyruvate were normal. Brain MRI (IMAGES) revealed right middle cerebral peduncle asymmetry and increased T2 signal in bilateral inferior olives. Brain PET scan showed symmetric activity in bilateral hemispheres with slightly decreased metabolic activity in the right thalamus compared to the left. His atypical neurologic findings in conjunction with marked inability to achieve sleep raised concern for the rare prion disease, sporadic fatal insomnia. Genetic analysis for fatal familial insomnia was negative, though there was homozygosity for the methionine-methionine polymorphism at codon 129.

RESULTS: Brain autopsy confirmed a diagnosis of Leigh's disease based on neuropathologic findings and morphology.

CONCLUSIONS: This case illustrates instructive clinical, imaging, and pathologic features of adult-onset Leigh's disease. Furthermore, it highlights that Leigh's disease should be included in the differential diagnosis of adult patients presenting with rapidly progressive encephalopathies and movement disorders for whom prion disease is considered.

Disclosure: Dr. Pal has nothing to disclose. Dr. Goldman has received personal compensation for activities with American Academy of Neurology, Movement Disorder Society, Johns Hopkins Dystonia and Spasticity Practicum, and Teva. Dr. Goldman has received research support from NIH/NINDS and the Parkinson's Disease Foundation.