Sleep Disorder May Signal Neuro Conditions to Come

Posted on Aug 31, 2010 in Chronic Disease

by Todd Neale

REM sleep behavior disorder — in which dreams are accompanied by excessive movement — may be a sign of neurodegenerative conditions like Parkinson’s disease that manifest several decades later, a case series showed.

Among 27 patients with Parkinson’s disease, multiple system atrophy, or dementia with Lewy bodies, the median time between the onset of REM sleep behavior disorder and symptom onset of the neurodegenerative condition was 25 years, according to Bradley Boeve, MD, of the Mayo Clinic in Rochester, Minn., and colleagues.

In one case, the time span reached 50 years, they reported in the Aug. 10 issue of Neurology. 

Previous studies have found that REM sleep behavior disorder precedes Parkinson’s disease and related conditions by about a decade in most cases, although there were occasional cases with a wider interval.  

“These cases illustrate that [the synucleinopathies] may have extremely long courses, with preclinical periods extending back decades in at least some cases,” the researchers wrote.

A long preclinical phase has important implications for epidemiologic studies, as well as for “the development of therapies that might slow or halt alpha-synucleinopathy progression, which could be implemented well before the cognitive and motor features are manifest,” they wrote.

In an accompanying editorial, Mark Mahowald, MD, of the Minnesota Regional Sleep Disorders Center in Minneapolis, and colleagues noted that new treatments — including pharmacologic, mechanical, and cell-based and gene therapies — hold promise for the synucleinopathies.

“In order to employ most effectively the promising new treatments … new quantitative assessments of both motor and nonmotor symptoms are needed,” they wrote. “The subtle and protean early nonmotor manifestations of the synucleinopathies must be identified early, allowing the use of effective neuroprotective treatments as they become available.”

The researchers used Mayo Clinic records to identify 27 patients with some form of synucleinopathy who had onset of REM sleep behavior disorder at least 15 years before neurodegenerative symptoms arose. The patients’ mean age at onset of the sleep disorder was 49 and at onset of neurologic symptoms was 72.

Among the patients, 13 had Parkinson’s disease with or without mild cognitive impairment or Parkinson’s disease dementia, 13 had dementia with Lewy bodies/mild cognitive impairment plus parkinsonism, and one had multiple system atrophy.

Most — 89% — were male.

REM sleep behavior disorder manifested itself for most of the patients through dreams in which the patients were defending themselves or running away from an attacking person or animal. The rest of the patients could not remember the details of their dreams.

Movements during sleep included punching, shouting, getting out of bed, or flailing arm movements.

The patients were evenly split between presentation of their neurologic condition through motor symptoms or cognitive impairment, with the exception of one patient who presented with autonomic symptoms.

At the latest follow-up, nearly two-thirds of the patients (63%) had developed either Parkinson’s disease dementia or dementia with Lewy bodies.

About three-quarters (74%) had concomitant autonomic dysfunction, which was mostly expressed as postural related lightheadedness but also included urinary incontinence or retention and constipation.

The researchers noted that in previous studies not all patients with REM sleep behavior disorder have eventually developed a synucleinopathy.

“However,” they wrote, “the current series documenting very long latencies raises a question whether all patients with REM sleep behavior disorder would later develop such neurodegenerative syndromes if they lived long enough.”

The authors acknowledged that the study — using a convenience sample of patients — cannot establish the incidence or prevalence of long intervals between REM sleep behavior disorder and the synucleinopathies.