Poor Extraocular Movements Linked to Decreased REM Sleep in Huntington Disease

Patients with REM sleep percentage less than 15% were associated with poorer horizontal optokinetic nystagmus grades and more severe illness.

Newly published research highlighted the significant sleep disturbances patients with Huntington disease (HD) face, while establishing an association between poor extraocular movements (EOM) and decreased rapid eye movement (REM) sleep. The findings also show an association between decreased REM sleep and increasing disease severity, which was concordant with the fact that gaze abnormalities continue to worsen as HD continues to worsen.

Senior author Ravi Yadav, MD, DM, professor of neurology, National Institute of Mental Health and Neurosciences, and colleagues used a combination of validated questionnaires complemented with polysomnography (PSG) to evaluate the impact sleep disturbances have on oculomotor abnormalities in a cohort of 29 patients with HD and 15 healthy controls. Based on total functional capacity (TFC) scores, there were 9 (31.03%) cases of mild HD, 16 (55.17%) patients with moderate HD, and 4 (13.79%) with severe HD. Sleep impairment was reported in all patients with severe HD, and 33% (n = 3) of those with mild HD. REM behavior disorder was reported in 5 patients.

Optokinetic nystagmus (OKN), found to be impaired in both vertical and horizontal directions in HD cases, was also affected in all patients who had severe HD. In total, 13% of patients with HD were completely absent of OKN.

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Due to markedly low sleep efficiency, 2 control PSGs and 3 HD PSGs were excluded from the analysis. Those with HD demonstrated higher median wake period and higher wake after sleep onset (WASO) percentage than the control population (P = .005), as well as a significantly higher percentage of patients with narcolepsy type 2 (N2) and a significantly high number of stage transitions in sleep (P = .007). Despite failing to reach statistical significance, investigators also observed slightly more sleep arousals in the HD group compared with controls.

After excluding the 2 patients with HD who lacked REM sleep data, mean REM sleep percentage was recorded at 11.68% (±6.9). Only 2 of the 23 patients with REM had sleep percentages above 20%, while 14 patients had REM sleep percentage less than 15%. Low REM sleep percentage—defined as those with less than 15%—was found to be associated with poor horizontal optokinetic nystagmus (OKN) abnormalities, defined as grades 2 and 3 (P = .02).

"Gaze abnormalities in HD leads to errors in identification of REM sleep and may falsely lead to decreased REM sleep percentage recorded in HD. However, pathological studies in HD patients will be essential to determine the pathological substrate of poor REM sleep,” Yadav et al wrote. "To understand whether REM sleep is indeed low in HD, we will require additional REM sleep parameters to be considered for REM sleep scoring in PSG of patients with EOM abnormalities like that seen in HD."

Investigators also observed that patients with low REM sleep were associated with severe illness, represented by scores of at least 25 on Unified Huntington’s Disease Rating Scale (P = .038). Despite this, low REM sleep had no association with poor vertical OKN, TFC, or CAG repeats.

The major limitations with this study included the small sample size, as well as the fact that all patients and controls underwent only 1 night PSG, which could have led to first night effect, according to the study authors. They also noted that a subjective analysis of eye movements using electro-oculography and details of REM sleep without REMs could have highlighted more details regarding REM sleep abnormalities in HD.

REFERENCE
Annapureddy J, Ray S, Kamble N, et al. The association of saccadic abnormalities with REM sleep in patients with Huntington disease. Sleep Med. Published Online November 12, 2021. Doi:10.1016/j.sleep.2021.10.035