What are the primary causes of REM (Rapid Eye Movement) behavioral disorder?

From the Guidelines

REM behavioral disorder (RBD) is primarily caused by dysfunction in the brainstem structures that normally paralyze muscles during REM sleep, with the most common causes including neurodegenerative diseases, particularly synucleinopathies like Parkinson's disease, multiple system atrophy, and Lewy body dementia, as well as certain medications and brain lesions. The causes of RBD can be categorized into several key areas, including:

• Neurodegenerative diseases: synucleinopathies like Parkinson's disease, multiple system atrophy, and Lewy body dementia, with RBD often appearing years before other symptoms of these conditions 1
• Medications: antidepressants (especially SSRIs like fluoxetine and sertraline), stimulants, and some beta blockers can trigger RBD 1
• Brain lesions: affecting the brainstem, particularly from strokes or tumors, can disrupt the normal muscle atonia during REM sleep 1
• Withdrawal from substances: like alcohol and sedatives may also precipitate symptoms 1
• Idiopathic RBD: in some cases, RBD occurs without an identifiable cause, though many of these patients eventually develop neurodegenerative disorders 1 It's worth noting that the most recent study on the management of RBD, published in 2023, provides conditional recommendations for the use of certain agents in the treatment of isolated RBD, including clonazepam, immediate-release melatonin, pramipexole, and rivastigmine 1. However, the primary focus of the question is on the causes of RBD, rather than its treatment. Some key points to consider when evaluating the causes of RBD include:
• The association between RBD and neurodegenerative diseases, particularly synucleinopathies
• The potential for certain medications to trigger RBD
• The role of brain lesions and withdrawal from substances in precipitating RBD symptoms
• The existence of idiopathic RBD, and the potential for these patients to eventually develop neurodegenerative disorders.

From the Research

Primary Causes of REM Behavioral Disorder

The primary causes of REM behavioral disorder (RBD) are not fully understood, but research suggests that it is associated with neurodegenerative diseases, particularly synucleinopathies such as Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy 2, 3, 4, 5, 6.

Neurodegenerative Diseases

• Parkinson's disease: RBD is a strong predictor of Parkinson's disease, with up to 40-65% of patients with idiopathic RBD developing the disease 4.
• Dementia with Lewy bodies: RBD is also associated with dementia with Lewy bodies, a neurodegenerative disease characterized by the deposition of alpha-synuclein in neurons 2, 3.
• Multiple system atrophy: RBD is a common feature of multiple system atrophy, a rare neurodegenerative disease 3, 6.

Other Factors

• Brainstem damage: RBD can be caused by damage to the pontomedullary brainstem structures, which can be triggered by pharmacologic agents such as antidepressants 4.
• Traumatic head injury: Repeated traumatic head injury may also contribute to the development of RBD 5.
• Post-traumatic stress disorder: RBD has been linked to post-traumatic stress disorder, although the exact mechanism is unclear 5.
• Antidepressants: Certain antidepressants can trigger RBD, particularly in patients with a history of traumatic head injury or post-traumatic stress disorder 4, 5.