Mysterious DNA modification important in fly brain

Drosophila, despite being a useful genetic model of development, have very little DNA methylation on C. What they do have is methylation on A (technically, N6-methyladenine), although little was known about what this modification did for Read more

Where it hurts matters in the gut

What part of the intestine is problematic matters more than inflammatory bowel disease subtype (Crohn’s vs ulcerative colitis), when it comes to genetic activity signatures in pediatric Read more

Overcoming cisplatin resistance

Cisplatin was known to damage DNA and to unleash reactive oxygen species, but the interaction between cisplatin and Mek1/cRaf had not been observed Read more

narcolepsy

Measuring sleepiness: alternatives to five naps

In a 2015 episode of The Simpsons, Homer is diagnosed with narcolepsy. Overwhelming sleepiness at the nuclear power plant lands him in the hospital. Sampling his spinal fluid (ouch!), Homer’s chuckling, deep-voiced doctor quickly performs a test for hypocretin, a brain chemical important for staying awake and regulating REM sleep.

Reality check: testing for hypocretin takes time, and is not currently available in the United States. Let’s talk about how sleep disorders such as narcolepsy and idiopathic hypersomnia are actually diagnosed: operationally, rather than biologically. The less flashy, but standard, way to assess patients is to ask them to take a series of five naps and see how fast they doze off, and how fast they go into REM sleep (the rapid eye movement dreaming phase).

This process, known as the Multiple Sleep Latency Test or MSLT, works pretty well for narcolepsy type 1, the more distinctive form of narcolepsy that includes cataplexy. And it’s hard to fake being sleepy enough to zonk out within a few minutes. But it has a bunch of problems, and dissatisfaction with the MSLT has been developing among sleep specialists for the last several years.

Lynn Marie Trotti, MD

At Emory, neurologists Lynn Marie Trotti and David Rye published an analysis of what I will call the “flip flop problem” in 2013, with others in the field following up more recently. The flip flop problem is: someone who takes the MSLT one day will frequently get another result if they take it again on a different day. Read more

Posted on by Quinn Eastman in Neuro 1 Comment

How much does idiopathic hypersomnia overlap with ME/CFS?

In everyday linguistic usage among non-specialists, sleepiness can blend together with tiredness and fatigue. Someone might feel “tired” after climbing a mountain or chopping down a tree, while “sleepiness” is different. Emory sleep scientists explore the pathological distinctions in a paper published in Journal of Sleep Research.

A team led by neurologists Lynn Marie Trotti and David Rye has been studying idiopathic hypersomnia (IH) for several years: people who experience excessive daytime sleepiness and “sleep drunkenness,” not explained by other medical conditions.

IH’s symptoms don’t usually include persistent muscle pain or a severe response to exertion. This separates the disorder from myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS). But there is some overlap, which is what neurology resident Caroline Maness, Trotti and colleagues report in the new paper. The authors use the official term SEID (systemic exertion intolerance disease), which was recommended by an Institute of Medicine panel in 2015, but hasn’t really stuck among those in the ME/CFS field.

Some people with IH have disclosed that they were previously diagnosed with ME/CFS. Outside of the sleepy vs tired issue, some people with IH report symptoms shared with ME/CFS, such as impaired circulation in their extremities in response to cold, or dizziness upon standing. Speculatively, this may point to a possible problem with the autonomic nervous system. Trotti and a collaborator at Stanford, Mitchell Miglis, are now examining this issue further.

ME/CFS has had a history of controversy. Despite its devastating impacts, some have viewed it as psychological or somehow unreal, and sufferers have felt neglected or maligned by mainstream medicine. The National Institutes of Health has made efforts to turn that situation around by investing in ME/CFS research, and there has been a surge of attention recently covering ME/CFS (Amy Maxmen items in Nature, Stanford magazine feature, Unrest documentary).

Trotti, Maness and colleagues didn’t set out to dive into ME/CFS – they explicitly label this paper a pilot study, and the results say more about the “hypersomnolent” group of patients they have been seeing for the last several years, rather than the broader ME/CFS population. Read more

Posted on by Quinn Eastman in Neuro Leave a comment

Momentum at hypersomnia conference

A visitor might not realize this was a meeting devoted to people who experience excessive daytime sleepiness. The 2015 Hypersomnia Foundation Conference on Saturday was full of energy, with:

*more than 245 attendees, about twice as many people as last year’s conference

*medical experts from France, Wisconsin and Louisiana — in addition to Emory

*data from several recent clinical trials

*some signs of industry interest in hypersomnia

Hypersomnia is a sleep disorder in which individuals feel frequent or constant sleepiness and need to sleep for long portions of the day (more than 70 hours per week). It is distinct from other sleep disorders such as narcolepsy and sleep apnea, but its prevalence is still unclear. Conventional stimulants such as amphetamine or modafinil often can be used to treat the sleepiness, but some with hypersomnia find these drugs ineffective or hard to tolerate.

Previous research at Emory has shown that many individuals with hypersomnia have a substance in their spinal fluid that acts like a sleeping pill, enhancing the action of the neurotransmitter GABA. The identity of this mysterious substance is unknown, but Emory researchers report that they are close to identifying it. That could give hypersomnia a “molecular handle” similar to what narcolepsy has, with loss of hypocretin-producing neurons.

The terminology is still up in the air — keynote speaker Isabelle Arnulf from Paris said, “The term ‘idiopathic hypersomnia’ does not mean that you are an idiot.” Rather, she said, it means that even specialists can have trouble distinguishing hypersomnia from other sleep disorders, and “idiopathic” signifies that the detailed cause is still under investigation.

Read more

Posted on by Quinn Eastman in Neuro Leave a comment