Case Presentation:

A 60–year–old woman with no past medical history presented with sudden onset of confusion, mutism, agitation, and behavioral changes that were precipitated by a stressful family event. On initial presentation, she had no focal neurologic deficits but was completely non–verbal. She was noted to be restless, pacing around the room, and engaging in repetitive movements. Laboratory evaluation, including serum TSH, B12, folate and lactate, were normal. MRI of the brain suggested multiple areas of acute infarct in the right temporal lobe and bilateral T2 signal abnormalities in the basal ganglia with a normal MRA. A lumbar puncture demonstrated an elevated lactic and pyruvic acid. Additional family history revealed the patient’s daughter had been diagnosed with Leigh syndrome. Analysis of the patient’s blood revealed the same point mutation as her daughter (tRNA (Val) G1644A mutation) known to cause Adult Leigh Syndrome.

Discussion:

Leigh syndrome is a neurodegenerative disease that typically presents within the first month of life. However, it can present in adulthood due to the heteroplasmy of mitochondrial DNA. Leigh syndrome is often exacerbated by increased metabolic demand (fever, illness, stress). Leigh Syndrome is a heterogeneous disorder ranging from epilepsy to acute respiratory failure. The central nervous system is most commonly affected with psychomotor retardation, along with decline in cognitive function and psychiatric abnormalities. Most patients will have characteristic MRI findings of symmetric, bilateral lesions in the basal ganglia, thalamus, and brainstem. Evaluation for mitochondrial disorders includes genetic analysis, serum and CSF lactate and pyruvate levels, muscle biopsy and brain MRI. In one study, elevated serum lactate had a sensitivity of 62% for mitochondrial disorders; however, it is considered to be a non–specific marker. CSF lactate is more consistently elevated than serum lactate. Treatment is limited and is directed towards symptomatic treatment and replacing respiratory chain cofactors. Patients presenting with catatonia may benefit from a benzodiazepine trial. Antioxidants and exercise have also been shown to slightly reduce disease burden.

Conclusions:

Leigh Syndrome is a rare mitochondrial disorder, with onset usually brought on by increased metabolic demand or emotional stress. Although thought of as a childhood disorder, Leigh Syndrome can present in adulthood. This case reinforces the need for hospitalists to obtain a thorough family history and entertain a broad differential for unusual cases.