Sleep disturbances in chronic progressive external ophthalmoplegia

Chronic progressive external ophthalmoplegia (CPEO) is a relatively common mitochondrial disorder. In addition to extraocular muscle weakness, various other organs can typically be affected, including laryngeal and limb muscles, cerebrum, cerebellum, and peripheral nerves. Given this multi-organ involvement, patients are likely to be prone to sleep disturbances. Here, we determined the nature, prevalence, and determinants of sleep disturbances in CPEO.

We used validated questionnaires for various sleep disorders and possible determinants such as mood and anxiety, and we performed ambulant polysomnography (PSG) in 20 patients with genetically confirmed CPEO.

Three quarters of patients reported nocturnal sleep dysfunction. Thirty-five percent of patients fulfilled the criteria for restless legs syndrome, 30% excessive daytime sleepiness, and 70% significant periodic limb movements. PSG recordings revealed several indicators of a disrupted sleep architecture. Obstructive sleep disordered breathing was present in only one patient. However, four patients had an increased central sleep apnea index, all of whom had a polymerase gamma-1 mutation and a SANDO phenotype (sensoric atactic neuropathy, dysarthria, ophthalmoplegia). Physical examination and questionnaire outcomes were poor predictors of PSG results.

Several specific sleep disturbances are part of the phenotype of CPEO. Given that the disease is otherwise incurable, symptomatic treatment of sleep disturbances may be an important tool to improve quality of life. Therefore, patients with CPEO should be actively screened for sleep disorders, with a low threshold to perform PSG.