A 72-year-old, previously healthy man is brought to the office by his wife due to unusual movements and behavior during sleep that have occurred with increasing frequency over the past 3 months. She says, "Lately, he's been waking me up in the middle of the night, moaning and thrashing around like he's having a bad dream. Sometimes, he becomes so violent in his sleep that he'll kick and punch me. I can easily wake him up, but he's often confused for a few seconds. Then he usually describes a dream in which he was defending himself from an attack." Physical examination is unremarkable. Neurodegeneration due to accumulation of which of the following is the most likely etiology of this patient's condition?
This patient's repeated nocturnal episodes of complex motor behaviors that reflect dream enactment are consistent with REM sleep behavior disorder (RBD). RBD is a parasomnia characterized by dream enactment that occurs because the muscle atonia usually accompanying REM sleep is absent or incomplete. When awakened, patients may be transiently confused but very quickly become fully alert. They may not recall their movements during sleep but can frequently remember their dreams.
RBD is more likely to occur in men age >50 and is strongly associated with alpha-synuclein neurodegenerative disorders. Alpha-synuclein is a synaptic protein that accumulates in neurodegenerative conditions such as Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. Spontaneous (ie, not associated with medications) RBD is considered a prodromal syndrome of alpha-synuclein neurodegeneration because up to 90% of patients with idiopathic RBD eventually develop one of these conditions.
(Choices B and D) Extracellular accumulation of beta-amyloid and/or tau proteins occurs in Alzheimer dementia, which typically presents with early and prominent memory impairment with language deficits and spatial disorientation. Although sleep disturbances commonly occur in patients with Alzheimer dementia, they usually impact sleep initiation and continuity and occur later in the disease process.
(Choice C) Excessive accumulation of misfolded, infectious proteins (ie, prions) causes Creutzfeldt-Jakob disease, a fatal disease that most commonly presents with rapid mental deterioration, behavioral abnormalities, and myoclonus.
(Choice E) Accumulation of abnormally ubiquitinated TAR DNA-binding protein-43 (TDP-43), which normally functions as a transcription inhibitor and DNA repair protein, is associated with both amyotrophic lateral sclerosis and frontotemporal dementia. Patients with amyotrophic lateral sclerosis frequently have sleep difficulty, which is usually related to an inability to change position due to muscle weakness, pain due to muscle cramps, and comorbid anxiety.
Educational objective:
REM sleep behavior disorder (RBD) is a parasomnia characterized by dream-enactment behaviors due to a loss of atonia during REM sleep. Most patients with idiopathic RBD eventually develop a disorder of alpha-synuclein neurodegeneration, most commonly Parkinson disease.