Ira Goodman, MD, an Adult Neurologist also associated with Compass Research Bioclinica Research, talks about REM Sleep Disorder.
Interview conducted by Ivanhoe Broadcast News in April 2017.
First off, what is Compass?
Dr. Goodman: Compass Research is a clinical research organization started over a decade ago that contracts with pharmaceutical companies to conduct their clinical trials. These clinical trials range from early stage development that confirms safety and drug metabolism all the way to phases 3 and 4 which determine if the medication works and how well it works.
But you also you split it between research and clinic. So you do see patients?
Dr. Goodman: Correct.
Let’s start it by asking you about Lewy Body Dementia. Could you give our viewers an idea about what this is?
Dr. Goodman: Lewy body dementia is the second most common cause of dementia in the United States second only to Alzheimer’s disease. It consists of a combination of cognitive impairment and a movement disorder which has Parkinson’s disease features. The pathology of Lewy body dementia is different than seen in Alzheimer’s disease, with the primary pathology in Lewy body dementia being that of a misfolded protein called alpha synuclein. Both Lewy body dementia and Alzheimer’s disease are clinical diagnoses and frequently are difficult to clinically separate, particularly early in the disease process and in fact almost a quarter of people who have Lewy body dementia are initially misdiagnosed. In addition, the nomenclature for “Lewy body dementia” is a bit confusing. Under the umbrella of “Lewy body dementia” there are two separate types, 1 termed “dementia with Lewy bodies” and the second termed “Parkinson’s disease dementia”. These two subtypes are distinguished by the sequence of onset of symptoms, though both are characterized by the same pathologic changes i.e. alpha synuclein.
So a patient with this disease could have let’s say several forms, it could mimic that Parkinson’s-like symptoms too? Could you just explain that again for me please?
Dr. Goodman: Absolutely because these disorders in general are clinical diagnoses, the diagnosis is based primarily on signs and symptoms. Many of the signs and symptoms overlap in these various disorders that we term “dementia”. Dementia itself is not a disease but a syndrome characterized by cognitive impairment that is severe enough to interfere with a patient’s function. As mentioned Lewy body dementia is the second most common cause of dementia in the United States being second only to Alzheimer’s disease.
Let’s talk a little bit about REM sleep disorder, did the signs show up first if it’s an early potential indicator or Lewy Body?
Dr. Goodman: REM sleep behavior disorder is a very interesting disorder, first described about 30 years ago and characterized by abnormal vocalizations and movements during dreaming. Typically when we are asleep and dreaming we lose muscle tone and don’t move. We dream during what is termed “REM sleep” which we experience about 2 hours per night and nature was very clever, not allowing us to move during our dreaming to avoid injury to ourselves or others. People however with REM sleep behavior disorder lose this loss of muscle tone and literally act out their dreams. The movements can vary, sometimes represented by only a small arm movement or a vocalization. However sometimes the movements can be very drastic involving the patient falling out of bed and hurting themselves as well as literally attacking the bed partner during the dream enactment behavior. There have been several injuries associated with REM sleep behavior disorder including head trauma/brain bleeds as well as bone fractures. It has been reported that up to two thirds of bed partner have been injured during an episode of REM sleep behavior disorder by the bed partner. It is not a benign condition.
Will the patient wake up and remember for the most part?
Dr. Goodman: Most people in REM Sleep Disorder when they wake up, they will remember their dream. The dreams are very, very challenging. They are very violent frequently. The patient feels that somebody’s chasing them or hurting them, this is why they fight back and they kick. It’s more common in men and we’re not sure why. It’s interesting it seems like that when women have REM Sleep Disorder the dreams seem a little less violent. That’s not clear. But REM Sleep Behavior Disorder is a disorder of older people, 50 or over and is basically divided into two parts. There’s what they call idiopathic REM Sleep Behavior Disorder where it’s just isolated. But there’s a secondary which is more common and people who develop REM Sleep Behavior Disorder have a very significant risk down the road of developing Parkinson’s disease or Lewy Body Dementia. Parkinson’s disease and Lewy Body Dementia have the same pathology that misfolded Alpha-synuclein protein. It just depends where that misfolded protein is, how it manifests.
Do we know why the higher risks of developing Lewy Body or Parkinson disease?
Dr. Goodman: It’s probably related to alpha synuclein. In fact if you look at a person who has REM sleep behavior disorder, many of these patients will actually show other early nonmotor manifestations such as loss of sense of smell or constipation. These signs and symptoms are very common and taken in isolation probably have no significance with regards to future development of Lewy body dementia, but in retrospect these nonmotor manifestations can occur years before the full clinical manifestations of the disorder. There are reports of people with REM sleep behavior disorder who have the misfolded alpha synuclein protein deposited in their colon and salivary glands.
What symptoms should people look for and partners look for if your spouse is having a violent dream once, okay it happens. But if this is repeated is that cause for concern?
Dr. Goodman: Well it is important to get a sleep study performed because there are mimickers of REM sleep behavior disorder. For example people who have obstructive sleep apnea may stop breathing and are jolted awake can have agitated behavior on awakening. In younger patients movements during sleep could represent certain types of seizures. The only way to distinguish what is causing the movements is to obtain a formal sleep study.
Once doctors if they do diagnose this disorder what are the treatments, what’s available?
Dr. Goodman: There is no FDA-approved treatment for REM sleep behavior disorder. A medication that frequently is used effectively is Klonopin. This is in the class of the benzodiazepines like Valium Ativan and Xanax. In this class of medication Klonopin seems to work the best. The problem with Klonopin and these other agents is that they are frequently needed in older patients who are more prone to the side effects of these drugs and can have significant side effects such as worsening cognition, sedation, increased falling risks as well as even possibly paradoxical agitation. Likewise if these agents are used long-term, they must be gradually tapered to avoid withdrawal symptoms. Melatonin at doses of 2-3 mg may be effective in some patients for REM sleep behavior disorder. Sometimes melatonin is used in conjunction with Klonopin.
There is a trial ongoing?
Dr. Goodman: There is an ongoing clinical trial with an investigational drug called Nelotanserin. This medication blocks a certain receptor (5HT2A) which we feel plays a role in the pathogenesis of REM sleep behavior disorder. There may be a link between the dreams noted in REM sleep behavior disorder and the very prominent daytime visual hallucinations seen in Lewy body dementia and in fact Nelotanserin is being studied to also treat the visual hallucinations seen in Lewy body dementia.
Can you talk to me about Orvis?
Dr. Goodman: Orvis is a patient of mine who I’ve known for about five or six years. When he first came in I was very certain he had probably Alzheimer’s disease, the way he presented, he presented with cognitive impairment. But then when I looked at him, he seemed like he was developing a mild movement disorder. And actually I initially referred him for a clinical trial for Alzheimer’s disease but right before he entered I changed my mind. I said, I don’t really feel comfortable. And it turns out that with longitudinally following him it turns out he did have Lewy Body Dementia. And his dementia has progressed to a point where he’s very impaired but the REM Sleep Behavior Disorder has been an issue, an ongoing issue for years and it’s very distressing to his wife who we worked with for many years as well.
What can she do?
Dr. Goodman: Well number one she can protect Orvis and she can protect herself. People who have REM Sleep Disorder have side rails up, you move furniture away from the bed on the chance that, it’s a very high chance, they’re going to jump out of bed or try to get out of bed and like I said prevent herself from getting injury. There have been reports of people acting out dreams, actually trying to strangle their bed partner, or help them and protect them.
This drug is not helpful at the stage that Orvis is at?
Dr. Goodman: Unfortunately he could not enter the trial due to his advanced cognitive impairment.
How critical is it that there be more tools in the toolbox for doctors like yourself?
Dr. Goodman: Alzheimer’s disease is the #1 cause dementia in the United States with Lewy body dementia being the #2 cause. We currently have only symptomatic treatments available for Alzheimer’s. For Lewy body dementia we currently have no FDA approved treatments. There is a pharmaceutical company, Axovant which is dedicated to addressing the underserved area of Lewy body dementia. They are in fact the sponsors of three clinical trials for the treatment of Lewy body dementia.
Is there anything I didn’t ask you that you want to make sure people know?
Dr. Goodman: We are now on the cusp of developing treatments that address diseases that in the past have been untreatable. We have several symptomatic therapies for Alzheimer’s disease and now are encouraged that we may soon have effective symptomatic treatments for Lewy body dementia. We also now are optimistic that we will soon have treatments that can actually treat/modify the diseases themselves, not just mask the symptoms. For potential “disease modifying treatments”, it is important to begin treatment (if they are effective) as early as possible as these neurodegenerative disorders have been pathologically present for many years. As previously mentioned REM sleep behavior disorder is a very common frequently very early manifestation in patients who down the road will develop Lewy body dementia or Parkinson’s disease and if we can determine whether or not the REM sleep behavior disorder is indeed a signal for the later development of Lewy body dementia or Parkinson’s disease in that individual patient, we could potentially begin treatment at that very early “preclinical stage” when a disease modifying treatment is available. There are ongoing efforts to develop “biomarkers” that could help predict if the patient with REM sleep behavior disorder will later develop Lewy body dementia or Parkinson’s disease.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
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