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A Soothing Balm: Healing a Painful Experience

I want to add a postscript to my Personal Journey story that appeared in the July 2017 edition of the HF’s SomnusNooze. Karen BergerIt relates to the traumatic experiences I had due to my idiopathic hypersomnia and being hospitalized. Because of the letter I wrote and sent to the hospital where I had surgery, a care process is being developed for people who are hospitalized with hypersomnia. Amazing! I still get tears of joy when I think of it.

I feel compelled to share with the hypersomnia community the follow-up letter that I sent to the administrative staff at the hospital. I especially want others diagnosed with hypersomnia to know that speaking up and sharing our stories can have a very powerful, positive impact. Our stories serve to help others understand our challenges living with the symptoms of hypersomnia.

Dear XXXXXX,

I want to share how grateful and thankful I am for your response to my letter about my hospital stay at XXXX last November. Receiving the phone call from you and the subsequent letter from XXXX has felt like a soothing balm has been poured over a very painful area of my life; this experience has been incredibly healing. I have shed many tears of joy recently.

Moving from being very confused about the trauma I felt, to finally understanding it, was very difficult work, especially because I was dealing with so many other medical issues as well my idiopathic hypersomnia. Sending the letter to the hospital was difficult as I felt extremely vulnerable; I had no idea of how the hospital would react. Therefore, having the additional closure of knowing the hospital understands what I experienced is absolutely amazing. I do not have adequate words to describe how this feels. Knowing that XXXX Hospital is actually formulating some sort of care plan for when people with hypersomnia arrive at the hospital is exactly what I hoped would happen; I am so thrilled that this is actually happening.

The hospital’s response is even more precious to me because I recognize that that hospital staff conducted a serious, in-depth examination of the issues involved. This response was not a knee-jerk reaction to my letter. I suspect that someone probably examined my hospital records to see if there was evidence noted about the issues I talked about. I know that you talked to all my doctors; I was able to talk to Dr. XXXX briefly about the situation, and she assured me that a care plan was going to be worked on.

I shared my story with the Hypersomnia Foundation (HF) as well. In doing so, I realized that I described an issue that is much larger and more important than my individual experience at XXXX Hospital. Many in the hypersomnia community have not thought about issues relating to hospitalization and IH. As a result of my story being shared in the HF’s SomnusNooze, I have been told that there are many doctors and sleep researchers who now have a higher level of awareness of this issue. I now very seriously doubt that ANY hospital, ever, has identified a care process for people with hypersomnia. I have, however, through social media, connected with people with hypersomnia who have their own stories to tell about hospital visits. Here is the link to my story as presented there. Please note there are 2 articles:

http://www.hypersomniafoundation.org/share-your-journey-hospital-surgery-and-hypersomnia/

http://www.hypersomniafoundation.org/a-letter-to-my-health-care-system-about-hypersomnia/

I believe that your hospital, by choosing to address issues faced by those diagnosed with hypersomnia who are hospitalized, has now become a national leader among hospitals in dealing with patients who have this diagnosis. And for that, again, I am very grateful.

I want you to know that I am very willing to be involved and helpful in whatever way I can in the future.

Thank you,
Karen Berger

Posted in: Awareness, BeyondSleepy, Hypersomnia, idiopathic hypersomna, Share the Journey Stories, SomnusNooze

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Idiopathic Hypersomnia Standard Characteristics

It’s often a struggle to describe to others – sometimes to doctors – the essence of idiopathic hypersomnia.

Now, the Hypersomnia Foundation presents Idiopathic Hypersomnia Standard Characteristics. This one-page document, reviewed and approved by our Medical Advisory Board, summarizes the common characteristics of IH. We hope it will be helpful to the IH community – to read and to share with friends, families, physicians, and others.

Find it here: Idiopathic Hypersomnia Standard Characteristics

Posted in: Awareness, Hypersomnia, idiopathic hypersomna, SomnusNooze

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A LETTER TO MY HEALTH CARE SYSTEM ABOUT HYPERSOMNIA

BY: Karen Berger – MN-USA

I have had idiopathic hypersomnia (IH) since I was 15 and was finally diagnosed 11 years ago.  Since then I have been doing well on medication, although I still have ups and downs. But I can function. Last fall, I experienced severe abdominal pain and spent 12 days in the hospital, diagnosed with diverticulitis, sepsis, and pneumonia. I was very sick.  I had to have emergency surgery and during my stay in the hospital I was not medicated for my sleep disorder.

It has taken me months to unravel and process what happened during my hospital stay in November, 2016. I was inspired to write a letter to the patient advocate of the health system, and the doctors who treated me, describing my hospital experience. 

One problem with the first hospital visit was that there was no one to speak up for me when I could not.  But even if I had told them, the second problem was that I did not know how IH would express itself during my hospital stay, nor did I know about the problems with drug interactions. This is why I think hospitals need to have a way of flagging patients who appear with a hypersomnia diagnosis.

The following letter is a sample of one written to the hospital patient advocate, sleep doctors, primary doctor, general surgeon and hospitalists who treated me in the hospital because I felt it is very important for them to know what happened to me after surgery while in the hospital and during my post-op recovery.

 

Dear XXXXXXXXXXXXXXXXX,

I was hospitalized at XXXXXXXX Hospital from XXXXXXXX to XXXXXXXX, 2016.    I had wonderful care while at XXXXXXX.  Dr. XXXXXX is my hero for moving away from what I felt to be an unsafe situation, as well as doing an excellent job of saving my life.  The nurses cared for me really well, and I will always remember the soothing voice of the nurse when I woke up from surgery.  

However, while having major surgery would not be a pleasant experience for anyone, my experience at XXXXXX became emotionally traumatic.  I have idiopathic hypersomnia (IH), a sleep disorder that causes “sleep drunkenness,” excessive sleepiness, and varied levels of alertness, as well as anxiety, if not treated.   Of course, all these symptoms were present in full force while I was at XXXXXXX, as I was not taking my IH medication.  As I reflect upon my experience in the hospital, it was the additional interaction of the hypersomnia with everything else that was going on that turned my experience at XXXXXXX from a very unpleasant one to into a traumatic one.

I had never considered how a sleep disorder would affect a hospital stay.  While I was in XXXXXX, I was unable to process how it was affecting me.  It took me a while after I got home before I understood what had happened.  I am pretty sure everyone thought I was just really sick from the sepsis, which I was.  I recognize that there was no way for anyone to recognize the presence of the sleep disorder as a separate factor from the infection.  But I know how I feel when I am not on my medication, and thus, I was able to recognize the effects of the sleep disorder while in the hospital.  

While at XXXXXXX, there were several times that I felt trapped in my body, and totally unable to communicate.  I would go for hours in a state of barely being awake, and barely able to think.  I was having difficulty processing information; my friends noticed that I was really anxious because I working so hard trying to understand the surgery and other things that were going on.  I was reacting in panic to things that were happening elsewhere because I was not in control, and I was sobbing in my bed because I could not get help or figure out how things worked.   I was very agitated because I could not process things well, and I had several tearful conversations with the nurses.   I was being given instructions from the nurses, for example, to blow into the incentive spirometer, and I didn’t do it because I could not remember.   

Then there were the side effects to the medications I was being given.  The first one (to help with hot flashes) caused ocular migraines and insomnia, and then I was given a sleep drug to help me sleep.  I could not wake up the next day.  Thank goodness that I was able to get off the narcotic medication 2 days after surgery because my sleep doctor later told me that patients with idiopathic hypersomnia should not take a sleeping medication with a narcotic.  I was unable to communicate most of this to anybody while I was in the hospital.

I would like to propose a solution to prevent what happened to me from happening to others.  Obviously the primary consideration of the hospitalists and surgeons was to save my life, not to worry about my sleep disorder.  However, they need to be aware of the presence of this additional disorder when a patient presents themselves for care.  

What I would like to propose is this:

  1. When a patient comes in and has a diagnosis of some kind of hypersomnia an alert warning is activated. 
  2. Everyone treating a patient with hypersomnia would be informed that until the patient can be back on their medication(s) the symptoms associated with hypersomnia will be fully active.                   
  3. Even though the patient presents with another condition(s), special care must be taken with a patient having hypersomnia knowing that the patient cannot be assumed to be awake, competent, or remember anything until they are back on their medication(s).  
  4. An alert warning that medications may affect someone with a sleep disorder differently than expected with a list of known medications available.  
  5. The patient needs to be assured that the hospital is aware of their hypersomnia diagnosis and they are committed to take care and use precaution until the patient with IH can be back on their medication(s).  (I think had I been told that the nurses and doctors recognized that I had a sleep disorder, and that they understood the symptoms, it would have made all the difference in the world).  

I know that other patients with hypersomnia will be very grateful if, in the future, their unique needs are recognized as a part of their care while in the hospital.  I hope this will be informative and helpful so that a process can be developed for people with hypersomnia while in hospital.

 

Thank you,

Karen Berger

 

Posted in: Hypersomnia, idiopathic hypersomna, Share the Journey Stories, SomnusNooze

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SHARE YOUR JOURNEY

Your Story Matters

Everyone has a story to tell that will resonate, educate or motivate.

Coming to terms with having a rare, chronic condition can feel like a long and sometimes lonely process. Knowing others have walked a similar road as you, however, can help lessen the burden. Understanding another’s’ experiences, coping strategies, and challenges or successes can help people who are currently struggling.

A feature of the Hypersomnia Foundation’s SomnusNooze is the “Share Your Journey” segment—told from the perspective of a person with hypersomnia, a supporter, or healthcare professional. Will you share your struggles, triumphs, diagnostic journey, or coping strategies?

Sharing your journey is like extending a hand of support.

Did you find the words that made a doctor finally listen? Have you developed specific coping techniques that help at work, school or for social events? Do you recall how you felt when you realized that you are not alone in your struggles with the symptoms of hypersomnia; as a patient, supporter or healthcare professional? Possibly you identified a new career or hobby that maximize your potential.

footsteps 
Sharing a specific story or personal experience about living with hypersomnia can be extremely powerful and healing, not only for the storyteller but also for readers. Your journey may be the key to someone dealing with hypersomnia, or a family member or friend, to say, “That could be me!” “I’m not just lazy!” “He’s/She’s telling my story!” “He/She gets exactly what I’m feeling!” or “I finally understand what my child is going through.”

Please share your journey by submitting approximately 500 words, or a series of stories/experiences, and if you are inclined, a picture (not necessary but it does tell 1,000 words) through: 

http://www.hypersomniafoundation.org/understanding-hypersomnia/share-your-journey/

 

If you would like to submit a video to tell your story/experience please contact us at:

 info@hypersomniafoundation.org

 

Posted in: Hypersomnia, idiopathic hypersomna, Journey, Share the Journey Stories, SomnusNooze

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Arise Clinical Trial

CLINICAL TRIAL ENROLLING PATIENTS WITH IDIOPATHIC HYPERSOMNIA AND NARCOLEPSY TYPE 2

Arise Clinical StudyBalance Therapeutics is evaluating an investigational new drug BTD-001, to treat excessive daytime sleepiness in individuals diagnosed with Idiopathic Hypersomnia (IH) or Narcolepsy Type 2 (Na-2).  A Phase 2 clinical trial is currently enrolling Na-2 subjects at 26 investigational centers in the United States.  Individuals currently diagnosed as “IH” who may have previously been diagnosed as narcolepsy may also qualify.  For more information regarding the study and participating site locations, and if you are interested in participating in this trial, please visit the website: www.arisestudies.com

Background:

Recent research published by a research team from Emory University in Atlanta, Georgia has demonstrated that the excessive daytime sleepiness in many individuals diagnosed with Idiopathic Hypersomnia (IH) and Narcolepsy Type 2 (narcolepsy without cataplexy; Na-2) is driven by accumulation of a naturally occurring substance, yet to be identified, that increases the function of the sleep promoting neurotransmitter γ (gamma)-amino-butyric acid (i.e., GABA) in the brain. 

The investigational drug BTD-001 is known to suppress GABA activity.  BTD-001 is therefore targeted more directly at emerging mechanisms thought to cause the excessive sleepiness of many patients diagnosed with IH and Na-2.  It is also unique from current FDA approved therapeutic approaches for alleviating the excessive daytime sleepiness in   individuals diagnosed with IH and Na-2.

To learn more information about the clinical trial and see if you might qualify, please visit the website: arisestudies.com

 

arise

 

Posted in: Action, Hypersomnia, idiopathic hypersomna, narcolepsy, Research, SomnusNooze

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Share Your Journey | Hospital, Surgery, and Hypersomnia

MY PERSONAL JOURNEY: Hospital, Surgery, and Hypersomnia

I want to shHospital and IH Journeyare my story because a recent experience has had a profound impact on me.  I am still processing it, and I think it is something anyone with hypersomnia needs to think about.  I never had.  I have had idiopathic hypersomnia (IH) since I was 15 and was finally diagnosed 11 years ago.  Since then I have been doing well on medication, although I still have ups and downs. But I can function. Last fall, I experienced severe abdominal pain, and spent 12 days in the hospital, diagnosed with diverticulitis, sepsis, and pneumonia. I was very sick.  I had emergency surgery and needed a colostomy.  

During my stay in the hospital I was not medicated for the sleep disorder, nor was I given other usual medications.  Imagine the impact of being very sick plus having sleep drunkenness, and being in and out of various states of awareness. The hospital stay became a traumatic event for me.  There were times I felt trapped inside my body, unable to communicate.  I felt terror and fear because I felt very unsafe.  I experienced severe anxiety because I was trying so hard to follow instructions, and understand what was going on.  Nurses were giving me instructions that I was unable to follow.  My friends were concerned because they did not think I understood the instructions for going home.  I was overwhelmed learning to care for the colostomy.  I was given new medications, which caused insomnia and scrambled my body’s circadian rhythm.  Then to help me sleep, they gave me Ambien, which left me unable to wake up for an entire day.  When I came home, I had severe insomnia for months, and my sleep/wake cycle was severely disturbed.  I was terrified of having the takedown operation.  It took me months to process what had happened.  

By the time I saw the colon surgeon for the takedown procedure, I had figured out what had happened.  I was able to inform her very clearly of my diagnosis of idiopathic hypersomnia, and how I function when I am not medicated.  I told all my friends about my sleep disorder.  Things went much better for the second surgery.  I was back on my medication the day after surgery.  The problem I am having this time is that I have realized that I am hypersensitive to opioid painkillers. One side effect is insomnia, so I am struggling to get back on an even keel.  But overall the experience was much better.

Doctors in the hospital do not understand hypersomnia, nor do they understand the impact of the treatments they are providing on a person with hypersomnia.  And who plans to spend 12 days in the hospital for an emergency visit that is out of their control?  

I have no idea of where to go with this, but sharing my story with other people who understand hypersomnia seems like a good place to start.  

Karen B – MN, USA

Posted in: Hypersomnia, idiopathic hypersomna, Journey, Share the Journey Stories, SomnusNooze

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Dr. Trotti Answers Questions on Diagnostics Relating to Hypersomnia

Dr. Lynn Marie Trotti answers questions about diagnostics relating to hypersomnia and concludes…

Q – What is the “gold-standard” for diagnosis of narcolepsy?  What about IH?

A – For narcolepsy type 1 (or narcolepsy with cataplexy), measurement of hypocretin levels in cerebrospinal fluid is the most specific, most definitive diagnostic test available.  It is a true “gold-standard” in that it measures the problem that is causing the symptoms (that is, patients with narcolepsy type 1 have symptoms because their brain can no longer produce hypocretin).  However, this requires a lumbar puncture, and not all sleep physicians perform this procedure.  Furthermore, clinical testing of hypocretin levels is not commercially available.  In contrast, the multiple sleep latency test (MSLT) is a widely available test.  Over time, MSLT diagnostic cut-offs have been changed to improve the ability of the MSLT to correctly diagnose cases of narcolepsy with cataplexy, and so this is the most widely used test for narcolepsy.  

Although diagnostic criteria for narcolepsy without cataplexy require a multiple sleep latency test and diagnostic criteria for IH can include results from a multiple sleep latency test, research suggests that the MSLT may not be ideal for diagnosing these conditions.  However, an optimal diagnostic test to replace the MSLT has not yet been developed and validated.

Q – Why is an 8-minute cut-off of mean sleep latency used for diagnosing Idiopathic Hypersomnia on the MSLT?

A – The use of an 8-minute sleep latency was an consensus decision made by the authors of the American Academy of Sleep Medicine’s International Classification of Sleep Disorders (ICSD).  In the 2001 revision to the original ICSD, a mean sleep latency less than 10 minutes was reported as typically present in patients with IH but was not a mandatory part of the diagnosis.  

However, by the time of the 2005 publication of the second edition (ICSD-2), this had been shortened to 8 minutes (and the 8 minute cut-off remains as one potential diagnostic criteria for IH in the current ICSD-3).  The authors of the ICSD-2 decided to use an 8 minute cutoff “to define sleepiness for diagnostic purposes” based on the fact that this cutoff appeared to be the best cutoff for diagnosing narcolepsy.  The underlying assumption they made was that an 8 minute cutoff should work well for IH diagnosis if it worked well for narcolepsy diagnosis.  

At the same time, however, they cited data that the average mean sleep latency in IH patients was 6.2 minutes, with a standard deviation of 3.0 minutes.  This implies that NOT all patients with IH have a mean sleep latency less than 8 minutes.  The apparent discrepancy between these two ideas was not explicitly addressed in the ICSD-2, although the authors did state in the text accompanying the diagnostic criteria that the mean sleep latency is “usually” less than 8 minutes in IH, and that sometimes additional diagnostic testing would be needed.  

This became more explicit in the ICSD-3, which now allows documentation of long sleep times to establish a diagnosis of IH in patients with a mean sleep latency > 8 minutes.  Whether the revised criteria are fully optimized for the diagnosis of IH remains to be determined.

Posted in: Hypersomnia, SomnusNooze

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BeyondSleepy in Boston 2017 a Success!

Saturday’s social gatherings kicked off with the Old Town Trolley Ride and ended the day with a casual Meet and Greet.  “This is the first time in my life I have ever met anyone else with hypersomnia let alone be able to sit and talk to them and share stories.  This has truly been life changing for me,” said one attendee.

 

Sunday’s HF Conference (#HFconf) welcomed all attendees and livestream viewers, both national and international.  The “Advocacy and Empowerment” theme presented through each speaker, addressed the various challenges for people with hypersomnia. One comment post-conference comment, “Thank you for your hard work.  I spent (many years) hiding my condition from the world and friends.  It was so difficult pretending.  Now I don’t have to.”

Our June 4th “Advocacy and Empowerment” conference video (unedited) is now available for a limited time on our YouTube channel, in 2 parts. #beyondsleepy #HFconf

https://m.youtube.com/channel/UCQyK93W4lilnzyVKeadzoug

 

We are sincerely grateful to our 2017 Boston conference sponsors.  Thanks to their support we were able, once again, to livestream as well as professionally record audio/video of this conference.  On behalf of the entire hypersomnia community we wish to thank Balance Therapeutics, Pavilion Compounding Pharmacy, Village Pharmacy of Lynnfield, and E. Matthew Steinberg, AIF – Oppenheimer.  

Posted in: Conference, Hypersomnia, SomnusNooze

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Flumazenil for the Treatment of Refractory Hypersomnolence

Background

In 2012, researchers from Emory University published a paper on their finding of a substance that increases the effectiveness of GABA in people with central disorders of hypersomnolence, particularly idiopathic hypersomnia. In that paper, they discussed their findings in seven patients who were treated with flumazenil. In 2014, Kelty et al published a case report on the use of flumazenil given intravenously to a single patient for 96 hours and then implanted under the skin. The current paper from the group of Emory researchers includes information from additional patients who were treated with a compounded version of flumazenil.

What kind of a study was this?

This was a retrospective study, meaning that the researchers did not set out ahead of time to perform a research study with predetermined goals and questions. Instead, two neurologists prescribed the medication, flumazenil, as part of their routine practice to all appropriate patients who came to their clinic. Then, at a later date, they formulated their questions.

Who were the patients and what did they do?

One hundred fifty-three patients (92 women) were prescribed flumazenil by the physicians at Emory.
sleepy
Their average age was 35.5 years. All of the patients completed the Epworth Sleepiness Scale (ESS) before starting treatment with flumazenil, and some patients completed a second ESS after starting treatments.

Who were the researchers and what did they do?

Dr. Trotti and her colleagues at Emory University reviewed the charts of their patients with hypersomnolence for whom they had prescribed flumazenil. They also reviewed the patients’ electronic correspondence and pharmacy records.

What were the results of the study?

Ninety-six of the 153 (63%) patients reported that they were less sleepy after taking flumazenil. On the other hand, 19 people reported that they were more sleepy after taking flumazenil. Among these 19 patients, nine continued taking flumazenil because the increased sleepiness was only temporarily worse right away after taking the medication or the sleepiness improved after the flumazenil dose was changed.

Before starting treatment, the average ESS score was 15.1, even among those who were taking wake-promoting agents. After starting treatment with flumazenil, the average ESS score dropped to 10.3 among the 40 people who reported improved sleepiness and who completed a second ESS.

awakeOf the 96 patients who reported that their sleepiness improved in response to treatment with flumazenil, 59 continued to take the drug long term (average, 7.8 months at follow-up). Interestingly, 72% of women reported a positive response to the drug, whereas only 48% of men had a positive response. Similarly, people who reported having sleep inertia (difficulty waking up, including grogginess or disorientation immediately upon awakening) were more likely to respond to flumazenil, as compared with those without sleep inertia (72% vs 42%).

Seventy-nine participants (52%) reported experiencing an adverse event (the most common being dizziness, anxiety, and headache), with 17 people stopping the medicine because of adverse events. Two patients had serious adverse events, and another had changes in liver function tests that resolved after stopping the drug.

What were the researchers’ conclusions?

According to the authors of this study, “In summary, our clinical experience in a large group of patients with treatment-refractory hypersomnolence demonstrates meaningful and sustained clinical response in a substantial fraction of patients. Important questions remain about optimal formulation, dosing, long-term safety, and effectiveness. Prospective, controlled studies, ideally with measurement of plasma or cerebrospinal fluid flumazenil levels, are clearly needed. However, our experience suggests the possibility of clinical use of flumazenil in carefully selected, severely affected patients lacking other treatment options.”

Trotti LM, Saini P, Koola C, LaBarbera V, Bliwise DL, Rye DB.  Flumazenil for the treatment of refractory hypersomnolence. J Clin Sleep Med 2016;ePub ahead of print.

Posted in: Flumazenil, Hypersomnia, idiopathic hypersomna, Research

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Hypersomnia Research-Where We Are And Where We Are Headed

During the presentation by David Rye, MD, PhD titled “What are the latest developments in research on idiopathic hypersomnia?” at the Beyond Sleepy in the Mile-High City Hypersomnia Conference, he pointed out that, while on the one hand without a known biological biomarker there is a large unmet clinical need for people with idiopathic hypersomnia, on the other hand a growing awareness garnering increasing interest and recognition within the medical community is gaining momentum.

Following is an abbreviated summary of his talk prepared by Dr. Michelle Emrich.  As Dr. Rye had mentioned this is not an all-inclusive list but specific highlights of recent development in research, collaboration, and treatments of idiopathic hypersomnia:

  • In the fall of 2016 The Emory University sleep research team and collaborators anticipate applying for a newly announced FDA orphan products natural history grant that has the possibility to yield $400,000/yr of additional financial support for up to 5 years.
  • Nearly half of chronic fatigue syndrome patients meet MSLT criteria for IH. Data not yet published. Population based control MSLTs (n=1019) summarized courtesy of E. Mignot vs. CFS (n=46) from Wichita, KS (Reeves WC, et al BMC Neurol (2006); 6:41).
  • Studies of non-sleepy controls indicate that nearly ¼ (22%) are asleep by 8 minutes, which demonstrates that MSLT based criteria of ≤ 8 minutes put forward by the International Classification of Sleep Disorders (ICSD) is poor at discriminating IH from controls (i.e., it is a “poor” test in lacking specificity).
  • 71% of IH with long sleep have MSLT > 8 min (i.e. considered to be normal), showing that MSLT based criteria also have poor sensitivity for rendering a diagnosis of IH (C Vernet and I Arnulf, Sleep (2009)).
  • A “cluster analysis” (i.e., unbiased probing for the degree of commonality ofsymptoms) by Sonka, Susta and Billiard suggests that IH and Narcolepsy Type 2 (NT-2) share more similarities than differences. (Narcolepsy with and without cataplexy, idiopathic Hypersomnia with and without long sleep time: a cluster analysis.  Sleep Medicine 16(2):225-31).
  • Dr. David Plante (U. Wisconsin) is continuing his work looking at hypersomnia in affective disorders (e.g., depression and bipolar disease). Sleep propensity in psychiatric hypersomnolence: a systematic review and meta-analysis of MSLT findings.  Sleep Medicine Reviews – in press (2016).
  • Dr. Plante has a five-year K23 training grant from the National Institutes of Health (NIH). Research
    • Aim #1: to probe for deficits in slow wave electroencephalogram (EEG) activity in depression with hypersomnolence as standard sleep variables demonstrate increased sleep duration with normal efficiency in major depressive disorder (MDD) with comorbid hypersomnolence.
    • Aim #2: increased EEG slowing during wakefulness. Global reductions in pre/post sleep waking theta frequency band in MDD without hypersomnolence (relative to controls and hypersomnolent group).
    • Aim #3: Investigate slow wave induction as a treatment strategy. Subject recruitment is planned for Fall 2016.
  • Dr. Plante has also been successful in getting a strategic research award from the American Sleep Medicine Foundation (ASMF) to test the usefulness of a multidimensional assessment in improving the evaluation and treatment of hypersomnolence. Questions he’ll be looking at with this research award:
  1. Do novel objective hypersomnolence measures incorporated into routine MSLT workflows capture aspects of hypersomnolence not quantified by current standards?
  2. Is the Hypersomnia Severity Index a valid subjective measure in patients referred for evaluation of suspected CNS disorders of hypersomnolence? This is a new index he’s developed.
  3. Do novel objective measures of sleepiness and the Hypersomnia Severity Index faithfully capture improvement with treatment?
  • Dr. Lynn Marie Trotti (Emory University) also has been awarded a K23 training grant from the NIH relevant to IH and hypersomnia.
    • Aim 1: Define functional neuroimaging signatures of pathological sleepiness of different etiologies (IH vs. Narcolepsy Type 1 during WAKE). She anticipates unique signatures by disease state diagnosis in FDG-PET regional hypo- metabolism. She hypothesizes that in the resting state functional magnetic resonance imaging (fMRI) will reveal increased connectivity within what has been termed the brain’s “default mode network” (DMN) whereas portions of this brain circuit will deactivate when subjects perform a simple cognitive task (N-back). Diffusion Tensor Imaging (DTI) – decreased fractional anisotropy will also be explored. Aim 2: Brain circuits underlying the symptoms of sleep drunkenness in IH will be explored with similar imaging modalities.
  • Dr. Andy Jenkins’ (Emory University Depts. of Anesthesia and Pharmacology) research continues to move forward. Midazolam and other drugs in the benzodiazepine class exert their sedative actions via gamma-amino-butyric acid (GABA) by binding between the alpha and gamma subunits of the GABA-A receptor. Dr Jenkins and his team are attempting to decipher precisely the presumptive somnogen that contributes to hypersomnia in many IH and NT2 patients that is acting on the GABA-A receptor. They are methodically exploring the % change in small, GABA-mediated current results after making single amino acid substitutions on the alpha2 subunit of the GABA-A receptor. So far they have successfully identified how small changes dramatically influence how well GABA does its job.
  • Is somnogen bioactivity specific to IH or might it be a biomarker for other origins of hypersomnia/hypersomnolence?  The large NIH R01 grant awarded to Emory University and Dr. Rye supports studying this by comparing IH & NT2 and their spinal fluids with clinical features and spinal fluids collected from sleepy and non-sleepy sleep apnea patients, and non-sleepy controls. They are also anticipating assessing Kleine-Levin-Syndrome (KLS) patients both when in and out of their episodes of hypersomnia.

In order to help discover/define the biological pathways in which the somnogen calls “home” as well as, ultimately, the very nature/structure/chemical identity of the somnogen itself, the Emory University sleep research team is collaborating with:

  1. Dr. Nicholas Seyfried – Assistant Professor in the Emory Dept. of Biochemistry is the lead investigator applying proteomic methods to spinal fluid samples.
  2. Dr. Art Edison – A University of Georgia (U) Georgia Research Alliance scholar is the lead investigator applying metabolomics methods to spinal fluid samples.
  3. Dr. Mark Bouzyk – Founder and Chief Scientific Officer of AKESOgen – is studying genetics
  4. Dr. Gary Bassell – Chairman of Emory’s Dept. of Cell Biology – is especially interested in studying myotonic dystrophy patients (in whom hypersomnia is a prominent symptom). RNA splicing abnormalities in myotonic dystrophy cause problems with proteins derived from RNA. The GABA 2γ receptor subunit in myotonic dystrophy because of this altered splicing yields a receptor more sensitive to the effects of the sedating benzodiazepine midazolam (see above).

Genetics/Molecular Biology– Daly DD and Yoss RE A family with narcolepsy (Mayo Clinic Proceedings (1959) 34:313-319). Dr Rye spoke about this during this conference as well as at the 2015 Hypersomnia Foundation Conference.   Four generations of this family were identified. Narcolepsy Type 1 is now known not to be as heritable as the sleepiness described in this family. Only 3 of 13 (16) of these family members exhibited cataplexy. So hypersomnia/hypersomnolence, not Narcolepsy Type 1, appears to be what’s being inherited in this family. Dr Rye also showed several smaller family trees collected at Emory, in which IH, Narcolepsy Type 2, and long sleepers cluster together in families.

Toward genetic research Dr. Rye/Emory has collected $187,500 in donation commitments to begin studies of the genetic components underlying IH and related disorders.  The overall goal is to raise $250,000 to fund these preliminary studies, and using this data to position themselves to apply for larger streams of NIH or foundation funding. They are in the process of collating samples and deciding how to best assign diagnoses given the diagnostic challenges alluded to above (e.g,  IH vs. Narcolepsy Type 2 vs. long sleepers).  The team is also discussing internally and with external collaborators what best first strategies to employ (Genome Wide Association Studies (GWAS) vs. whole exome sequencing [which would be feasible and possibly more fruitful with larger families inclusive of affected and unaffected individuals]).
Most comparable GWAS studies require  ~ 1000 samples. The Emory sleep program has 825 plasma samples, 783+ DNA samples, 473 CSF samples. Including DNA samples collected since November 2015 waiting cataloging into their larger biorepository.
Also, 11 patients with repeat CSF samples have been collected under different clinical conditions, which should be very useful for determining what features are unique to wellness vs. hypersomnia by way of proteomic and metabolomics comparisons.
Very recently skin biopsies h=are being collected to derive fibroblasts from which they are then able to morph into immature brain cells to study more intensively, and in a repeated manner.

Clinical Trials & Treatments:  Pentylenetetrazol (PTZ; aka BTD-001). This is an anti-GABA-A receptor study drug with mechanism action similar to that of clarithromycin.  It is being further developed/studied by Balance Therapeutics for the treatment of cognition and memory deficits in Down’s Syndrome as well as hypersomnia/hypersomnolence in IH and Narcolepsy Type 2.  Interestingly, PTZ is still available as one ingredient (viz., cardiazol) of a cough syrup available in Italy. This is the ongoing clinical trial with the acronym of ARISE. Www.arisestudies.com is the first industry sponsored clinical trial of any treatment seeking FDA approval for treatment of IH. This trial is testing the efficacy of Pentylenetetrazol (PTZ) in a rigorous, controlled, crossover, and blinded design.  ARISE is actively enrolling patients at > 20 centers including Emory University (see the website for participating centers). This drug has a long and substantial safety record (i.e,. Phase 1 requirement of safety in humans has already been established). A small, unblinded Phase IIa study – 5 subjects (3 IH and 2 Narcolepsy Type 2) each with hypersomnia responsive to clarithromycin and/or flumazenil demonstrated very promising results. So much so that the much larger Phase IIb study is moving forward necessitating recruitment of 120 subjects (60 each with IH and Narcolepsy Type 2).

Emory’s open label experience with flumazenil continues to be promising and publication of their “open-label” experience in an initial 153 treated patients is forthcoming. The paper was accepted June 27, 2016 publication in the Journal of Clinical Sleep Medicine. Beyond this experience which is limited to those patients seen and treated by Drs. Rye or Trotti prior to January 1, 2015, it is estimated that nearly 300 patients with hypersomnia resistant to traditional treatments with wake promoting drugs have been empirically treated with flumazenil through Emory’s outpatient sleep clinic alone.  Many additional physicians outside of Emory are increasingly prescribing flumazenil to their patients.

Much has transpired since the 1950’s when Dr. Bedrich Roth coined the term “idiopathic hypersomnia” and progress will continue as we work together and tease out understanding of the causes of idiopathic hypersomnia.

Posted in: BeyondSleepy, Conference, Education, Hypersomnia, Research, SomnusNooze

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