Hypersomnia Foundation

There’s A Doctor in the Hypersomnia House

A few weeks ago, we launched our latest Hypersomnia Foundation program – Ask the Doctor. We thank everyone who has sent questions and encourage you to send your questions to atd@hypersomniafoundation.org.

Some of the questions that we received made us think about the language that we use when talking about sleep disorders. I know what I mean when I use a word, and you know what that word means to you, but unless our words mean the same thing to both of us, unless we use a common language, we are not hearing clearly what the other person is saying. I might say I have hypersomnia and mean that I am sleepy, but to you it means that you sleep for a long time. Language in general and the language of sleep disorders not only has changed over the years, but also will continue to change. So, today, thanks to your questions, we will discuss a few of these terms and provide a little background on why there is so much confusion.

Question: What do we mean when we say hypersomnia?
Answer: Hypersomnia means literally too much sleep. The definition of what is “too much” sleep can be debated but has been defined at various times for medical purposes as more than 10 to 11 hours per day. In current medical use, the word hypersomnia is also used to mean simply excessive sleepiness, regardless of sleep time.

Question: What is the difference between hypersomnia and hypersomnolence?
Answer: The Hypersomnia Foundation uses the term hypersomnia to mean the condition of too much sleep. Likewise, the International Classification of Sleep Disorders, third edition, reserves the term hypersomnia to mean the specific syndrome of idiopathic hypersomnia and the term hypersomnolence for the more general condition of excessive sleepiness.

Question: What are the differences between the terms sleepiness and fatigue?
Answer: Doctors have struggled to define and measure what is meant by the word sleepiness, as compared with other commonly used words such as tired, fatigued, and lack of energy. In general, doctors define sleepiness as the experience of being more likely than most people to take naps during the day, sleep for long periods at night, or fall asleep at times that it is problematic to do so (for example, while driving, at work, or during a conversation). In contrast, fatigue is defined as a state of having low energy or having trouble remaining on the same task but not necessarily falling asleep or sleeping too much.

Despite this distinction, it has turned out to be very challenging to measure sleepiness and fatigue in clinical settings. Part of this challenge is reflected in the fact that individuals who have sleep disorders do not necessarily experience these as completely different states (that is, patients with hypersomnolence might experience both sleepiness and fatigue, as defined above). Further, they do not typically use words to describe their symptoms that fit with the above schema.

A classic research study of patients with sleep apnea (who were sleepy because they did not breathe properly at night) showed that patients were sleepy based on their ability to fall asleep quickly during a Multiple Sleep Latency Test (MSLT) but were more likely to say that they had fatigue, tiredness, or lack of energy than sleepiness.1 In this study, when asked to choose only one response to describe their symptom, about 40% of subjects chose lack of energy and only about 22% chose the term sleepiness.

Determining optimal measures of fatigue has not been any easier; researchers use no fewer than 8 different scales to measure fatigue. The Multidimensional Fatigue Inventory attempts to further divide fatigue into distinct parts such as general fatigue, physical fatigue, and mental fatigue, as well as reduced overall activity versus reduced motivation.

1. Chervin RD. Sleepiness, fatigue, tiredness, and lack of energy in obstructive sleep apnea. Chest 2000;118:372-9.

Posted in: Ask The Doctor, SomnusNooze

Leave a Comment: (0) →

Together We WILL Solve The Puzzle of Hypersomnia

Why did the Hypersomnia Foundation Board of Directors and volunteers work for more than two years with physicians and researchers to create a hypersomnia-specific registry?

Because, as David Meeker, President and CEO of Genzyme, has said, “Creating a registry of patients is the single most valuable action a rare disease community can take!”

And this community of which Mr. Meeker speaks is all of us—it’s the young people who have recently been diagnosed with hypersomnia and it’s people who have lived with these conditions for decades. It’s also those of us who support our loved ones who struggle with hypersomnia, helping them in any way that we can to dispel the fog that enshrouds them and crying with frustration that we can’t do more.

Why are registries so important?
Registries provide critical information, particularly about rare diseases. Uncovering that information makes a rare disease easier to study, increasing the probability that a treatment can be developed.

Typically, people with rare disorders are not geographically in the same place, making it difficult for scientists and medical professionals to gather information or samples from enough patients to study a rare disorder. However, a central registry helps to overcome that geography hurdle

Why would I take the time and use my limited energy to enroll in the registry and complete the questionnaires?

  • Your participation today will provide a brighter future for tomorrow. And don’t forget, it will help to fund research through the Hypersomnia Foundation Board of Director’s $50 contribution for every completed questionnaire. Your participation will also provide concrete help to researchers looking for answers.
  • The information about the central disorders of hypersomnolence will be housed in one location, accessible to any researcher anywhere in the world whose project is valid and approved by the Sanford Institutional Review Board.
  • One of the goals of a registry is to generate a hypothesis (a scientifically based idea) about which treatments might be effective. These hypotheses can assist the pharmaceutical industry (drug companies) to know which treatments to study in clinical trials.
  • Researchers who are interested in studying new treatments for hypersomnia can contact CoRDS, and CoRDS will then contact people who have checked the box during registry enrollment that they are interested in participating in additional research.

Who is paying for the Registry?
The CoRDS registry at Sanford is funded by philanthropy. All costs pertaining to the Hypersomnia Foundation’s hypersomnia-specific registry have been covered by the generosity of a donor who contributed funds restricted to use for the Hypersomnia Foundation Registry.

What can I do?
Go to the new Hypersomnia Foundation Registry page on our website at http://www.hypersomniafoundation.org/registry/. There you will find a variety of resources.

  • A list of frequently asked questions
  • Step-by-step instructions to enroll in the Registry
  • Tips to help you enroll in the Registry and complete the questionnaires
  • A video of Dr. Lynn Marie Trotti’s presentation, INFORMATION IS POWER, at the Hypersomnia Foundation’s regional conference in June 2016.

As Dr. Trotti said, “This Hypersomnia Foundation Registry is the single most important thing people with hypersomnia can do!”

Be counted, help solve the puzzle, and complete the CoRDS questionnaires today!

Posted in: SomnusNooze

Leave a Comment: (0) →

Complete the CoRDS Registry to Raise Funds for Research!

Hypersomnia Australia is designating September 5- 11th as Idiopathic Hypersomnia Awareness Week. Their theme this year is Improving Quality of Life.

We can’t think of a better way to improve the lives of people with Idiopathic Hypersomnia than to make a special push toward research and finding new treatments – and one day, a cure.

Throughout the month of September, YOU can have a big impact on working towards these goals. The Hypersomnia Foundation’s Board will donate $50 to the Foundation’s Restricted Research Fund for every person with hypersomnia (or a related sleep disorder) who completes the patient registry at CoRDS by September 30th!

So, by registering with CoRDS and completing the registry by the end of September, you score a double win: your completed questionnaire gives researchers another piece of the puzzle and you raise $50 towards funding research. (If you began the questionnaire but didn’t finish it, coming back to complete counts!]

Read on for more details and tips for completing the registry, and then click the CoRDS link below to get started today!

What is the Coordination of Rare Diseases at Sanford (CoRDS) registry?
“…CoRDS is a centralized international patient registry for all rare diseases.  The goal of the CoRDS registry is to connect as many patients and researchers as possible to help advance treatments and cures for rare diseases.” Be assured that your identity is completely confidential. Your personal information will be given an ID number, which will then be linked with your responses to questionnaires – no researcher or the Hypersomnia Foundation will ever be able to connect your personal information with your ID number.

Who should participate in the CoRDS hypersomnia-specific registry?
Any person diagnosed with a central disorder of hypersomnolence—idiopathic hypersomnia, narcolepsy type 1 or 2, or Kleine-Levin syndrome—can contribute valuable information. For example, researchers want to know which symptoms are more common to each of these disorders as well as those symptoms that affect everyone with one of these disorders.

If my identity is protected, how will HF know if I have completed the registry?
CoRDS will simply provide the number of registrations on of September 1st and 30th.

OK, I’m ready to make my contributions to research!!  How do I get started??
You can also complete registration via regular mail by calling CoRDS at (877) 658-9192 or sending an email to cords@sanfordhealth.org and requesting paper versions of the Registry materials. If you would like to complete it online, click the link below or copy it into your browser. (It works best with updated versions Internet Explorer, Google Chrome, or Mozilla Firefox.)

https://cordsconnect.sanfordresearch.org/BayaPES/sf/screeningForm?id=SFSFL

OK, I’m on the site – now what?

Step 1: You will be asked to answer some basic questions in a SCREENING FORM.

TIP: Once you have completed the screening form and clicked submit, on the next screen, your first name will become your user name. You will be asked to select a password and set up a security question. Please make note of these responses.

The next screen confirms that you have submitted your screening form, but you are not yet enrolled.

Step 2: : Click the button at the top of the screen that says, Start Questionnaire.

TIP:  click on the SAVE & NEXT button in the upper right-hand corner of the screen to proceed to the next set of questions. Some people had a hard time finding how to proceed.

TIP: A question requires you to calculate your age at time your symptoms began. Here is a link to an online calculator to help determine age: http://images.pearsonclinical.com/images/ageCalculator/ageCalculator.htm

Step 3 – the most important part!: The final piece is the Hypersomnia Questionnaire. Please be as complete as possible in answering these questions. Although none of the questions are required, researchers may not be able to use your responses in their work if you do not answer all of the questions.

TIP: Take your time. Take a breather. You can save the questionnaire at any point, close out and log back into the registry at a later date in (if you remember your user name and password). Even if you have clicked SUBMIT at the end of the questionnaire, you can go back at any time and update your answers.

TIP: The questions do not get harder as you go along! In other words, if you come across a couple of tough questions, don’t assume that the rest of the questions will be difficult. Some people find it easier to go through the entire questionnaire to answer all the “easy” questions first, taking note of which questions they need to come back to and complete.

TIP: Because you can move onto the next page even if you have not answered all of the questions on your current page, please review your answers or make note of those questions that you have not answered before saving and clicking to the next page.

TIP: Some of the “pages” are long. Please scroll to the bottom of each page to “submit.”

TIP: Depending on your diagnosis, you might be invited to participate in additional questionnaires from other organizations. It is entirely up to you if you complete those questionnaires.

ONCE YOU HAVE COMPLETED EVERYTHING AND CLICKED SUBMIT – CONGRATULATIONS!

You’ve made a very valuable contribution to solving the puzzle of Hypersomnia. And if you have completed your questionnaire by September 30th, you’ve also earned $50 for research!

We are most grateful to the members of the PAAC (People with hypersomnia And Advocates Council), who have completed the Registry and provided these valuable tips. If you have any questions about the enrollment process or how to complete the three steps, please contact CoRDS at (877) 658-9192 or cords@sanfordhealth.org

If you have already completed the CoRDS registry, fantastic! Please help get the word out to the hypersomnia community and encourage others to take part and complete it. If not, please enroll in the Hypersomnia Registry at CoRDS today. Your enrollment during the month of September will provide answers and simultaneously fund research. Together we can solve the puzzle of hypersomnia one piece at a time!

Posted in: CoRDS Registry

Leave a Comment: (0) →

Ask the Doctor

Is There a Doctor in the House?

Yes!

The Doctor Is in and Here for YOU!

The Hypersomnia Foundation is pleased to announce the launch of a new resource for readers of SomnusNooze called Ask the Doctor.

The Nuts ‘n Bolts of Ask the Doctor

What is an Ask the Doctor column?
Ask the Doctor columns, or some form thereof, typically appear in medical newsletters for public consumption and address medical matters of interest to the readership.

How will the Hypersomnia Foundation’s Ask the Doctor column work?
Readers will submit their questions to atd@hypersomniafoundation.org. We reserve the right to modify your questions so that they apply to a broad audience and for grammar and clarity.  Members of the Foundations Medical Advisory Board will answer the questions, which we will then publish in SomnusNooze.

What kinds of questions can be submitted?
Questions that will be accepted for the column are those that are of general interest to the readers. However, they must be related to one of the three central disorders of hypersomnolence: idiopathic hypersomnia, Kleine-Levin syndrome, or narcolepsy. We cannot take questions that are related to a personal diagnosis or personal treatment. In other words, questions that seek medical advice will NOT be considered.

Who are the physicians behind Ask the Doctor?
As mentioned previously, members of the Hypersomnia Foundation’s Medical Advisory Board will be responding to these questions. You can see a complete list of our Medical Advisory Board on the Hypersomnia Foundation’s website at http://www.hypersomniafoundation.org/about-us/medical-advisory-board/.

We thank the members of our Medical Advisory Board for their willingness to be available to our readers and support the Hypersomnia Foundation in yet another way.  And, we thank YOU, our readers, for making this resource as robust and helpful as possible.

Introducing New Members of the Hypersomnia Foundation Medical Advisory Board

The Board of Directors of the Hypersomnia Foundation is thrilled to announce two additions to the Medical Advisory Board: Dr. Jason Ong and Dr. Michel Lecendreux. If you attended the 2016 Beyond Sleepy Regional Conference in Denver, or watched the Livestream, you have already “met” these two sleep clinicians. This month, we will formally introduce you to Dr. Ong and, next month, to Dr. Lecendreux.

Dr. Jason Ong is an Associate Professor of Neurology at Northwestern University Feinberg School of Medicine. He received his PhD in clinical psychology from Virginia Commonwealth University and completed a fellowship in Behavioral Sleep Medicine at Stanford University Medical Center. His primary research interest involves demonstrating the effectiveness and value of behavioral treatments for sleep disorders, including cognitive-behavioral therapy and mindfulness meditation. Specifically, Dr. Ong is interested in the psychosocial impact of hypersomnia, and his lab has been developing an intervention to aid in coping with chronic hypersomnia. Additional research interests include the impact of sleep disturbance on chronic health conditions. His clinical interest is aimed at delivering empirically supported behavioral treatments to patients with sleep disorders, which complements and informs his clinical research. Dr. Ong is currently the president-elect of the Society for Behavioral Sleep Medicine.

Posted in: SomnusNooze

Leave a Comment: (0) →

Service and Therapy Animals — Part 1: Getting Started

We begin this three-part series with a basic overview of the different types of service, emotional support and therapy animals.

therapydogSo, you’re thinking about getting, or someone has recommended that you get, a service dog, therapy animal, or emotional support animal (ESA). Or perhaps you have reached the decision that you need a service animal to help with your disability. Whether you self-train your animal, work with a professional trainer, or obtain an animal that has already been trained, ask a million questions to make sure that you have all the information you need. Getting an animal is at least a 10-year commitment for you and a lifetime commitment for your animal.  There are differences among the three main types of “working” animals. The following information will help you distinguish among these three types.

  • A service dog (can also be a miniature horse with some stipulations) is any dog that has been individually trained to do work or perform tasks for the benefit of an individual with a disability that they cannot do for themselves because of their disability. There are many types of service dogs and many different types of tasks that they might be asked to perform. A service dog does not have to be tested, registered, or insured and has access to most places where the general public is allowed.
  • A therapy dog (or other therapy animal) is tested, registered, and insured to go with its owner to visit facilities, such as hospitals, nursing homes, and schools, and to participate in reading-to-children programs. These animals are only permitted where they have been invited, and permission has to be obtained from the organization the animals are visiting. In addition, documentation of training of the animal by a reputable organization must be provided to the organization.
  • An ESA is a dog or other common domestic animal that provides therapeutic support to a disabled or elderly owner through companionship, nonjudgmental positive affection, and a focus in life. If a doctor determines that a person with a disabling mental illness would benefit from the companionship of an ESA, the doctor writes a letter supporting the person’s request to keep the ESA in “No Pet” housing or to travel with the ESA in the cabin of an aircraft. ESAs are not task-trained service animals. ESAs do not have to be tested, registered, or insured, but people who have an ESA require a letter from a doctor stating their need.

Only a judge can truly determine whether a person is legally disabled. Should the case arise in which a person with a service animal is brought to task, that person must be able to show that they are indeed disabled and that their service animal performs tasks to help with their disability—tasks that the person cannot do.

To begin, you should discuss getting a service dog or with your medical caregivers and think about your living arrangements and whether you have the financial resources to have a service dog. To find a service dog program or trainer, you can begin your search on the Internet, but remember, just because the program or trainer appears on a list on the Internet, it does not mean that the program or trainer is qualified. You still need to do more research.

Kimberly Brenowitz is a volunteer with Animals Deserve Better, Inc., and Paws for Life in Marietta GA. She can be reached at adb@animalsdeservebetter.com.

Posted in: SomnusNooze

Leave a Comment: (0) →

What’s New in the Diagnosis and Treatment of Hypersomnia in 2016?

Rather than writing our own article for this week’s edition of SomnusNooze, we are bringing you information from Dr. David Cunnington in Melbourne, Australia. Dr. Cunnington has agreed to share with us a recent post from his website (sleephub.com.au) that covers hypersomnia-related topics from the SLEEP2016 meeting in Denver. A podcast, which covers hypersomnia and other SLEEP2016-related topics, is available at sleephub.com.au/podcast (click on Sleep 2016 Update).

From Dr. Cunnington
In clinical practice it can be difficult accurately diagnosing people with hypersomnia and excessive sleepiness. Apart from narcolepsy with cataplexy, or type 1 narcolepsy, where there are distinct symptoms, and the possibility of testing orexin levels in cerebrospinal fluid, it can be hard to make an accurate diagnosis. Managing people with hypersomnia can also be difficult, as a substantial proportion of people are refractory to treatment with currently available wake-promoting medication.
Issues around diagnosing and treating hypersomnia were discussed at the recent Sleep2016 meeting in Denver, and I’ve tried to summarise some of the main issues that were covered.

Issues With Diagnosing Hypersomnia
The International Classification of Sleep Disorders 3rd Edition (ICSD-3), divides central disorders of hypersomnolence into narcolepsy type 1 (with cataplexy), narcolepsy type 2 (without cataplexy), idiopathic hypersomnia (IH) and then a range of other hypersomnias secondary to medical or psychiatric conditions or medications and the rare condition, Kleine-Levin syndrome.
The criteria for the diagnosis of IH listed in ICSD-3 are:

  • The patient has daily periods of irrepressible need to sleep or daytime lapses into sleep occurring for at least three months.
  • Cataplexy is absent.
  • A Multiple Sleep Latency Test (MSLT) performed according to standard techniques shows fewer than two sleep-onset REM periods or no sleep-onset REM periods if the REM latency on the preceding polysomnogram was less than or equal to 15 minutes.
  • The presence of at least one of the following:
    • The MSLT shows a mean sleep latency (MSL) of ≤ 8 minutes.
    • Total 24-hour sleep time is ≥ 660 minutes (typically 12–14 hours) on 24-hour polysomnographic monitoring (performed after correction of chronic sleep deprivation) or by wrist actigraphy in association with a sleep log (averaged over at least seven days with unrestricted sleep).
  • Insufficient sleep syndrome is ruled out (if deemed necessary, by lack of improvement of sleepiness after an adequate trial of increased nocturnal time in bed (preferably confirmed by at least a week of wrist actigraphy).
  • The hypersomnolence and/or MSLT findings are not better explained by another sleep disorder, other medical or psychiatric disorder, or use of drugs or medications

Whilst people with narcolepsy type 1 can usually be differentiated from these criteria, narcolepsy type 2 and hypersomnia associated with medical or psychiatric disorders can often overlap significantly with these symptoms. In addition, I often see people with most, but not all, of these symptoms. What do they have? They clearly have a problem, as they have been severely impacted by their symptoms and sleepiness. How much sleep and sleepiness is normal? Some surveys suggest around 8% of people sleep for more than 9 hours per day, and 1.6% of people report sleepiness intruding on their waking activities. One of the tests we commonly use, the MSLT, whilst helpful, can be negative in people with all the other symptoms of IH. In one study, 71% of people with long sleep times and other symptoms of IH had a mean sleep latency of > 8 minutes. In addition, unpublished data from Emory University has shown that around 50% of people with chronic fatigue syndrome meet the MSLT criteria for IH. Other studies have shown that 25% of people with hypersomnia due to psychiatric conditions have an MSL of < 8 minutes.

There really wasn’t any clear consensus on how exactly to define hypersomnias and IH. Unfortunately there are not good biological markers, and trying to make a definite diagnosis based on symptoms is fraught with difficulty. So an approach put forward by the team from Emory and that seems to make sense is to try to exclude other factors that can add to sleepiness symptoms, such as depression and circadian rhythm disorders, as well as getting a number of objective measurements of sleepiness and it’s impact. They do this by performing the below tests and assessments:

  • Multidimensional Fatigue Inventory – measure of fatigue
  • Short-form Beck Depression Inventory – measure of depression
  • Horne-Östberg Scale – measure of circadian phase
  • Psychomotor Vigilance Test – measure of alertness and response times
  • Sleep study and MSLT
  • CSF orexin / hypocretin – absent in narcolepsy with cataplexy
  • CSF GABA potentiation – significance of this is unclear

Although the team at Emory were testing cerebrospinal fluid levels of GABA potentiation in everyone with hypersomnia at one point, they are not doing this routinely at the moment and have found that people with sleepiness due to other causes such as sleep apnea can also have GABA potentiation, meaning that what they had previously described as a “somnogen” may not be specific for IH, but may in fact be a mediator of sleepiness symptoms in a range of conditions.

Options For People Refractory To Available Treatments

With regard to treatment, we often find people with IH are refectory to treatment, and some groups report around 50% of people on modafinil not persisting with treatment because of a lack of efficacy, and only 30% to 60% of people on dexamphetamine continuing with treatment. Given this, other treatments to address symptoms of sleepiness symptoms are needed.

Clarithromycin – has been used by the team at Emory who published their research in Annals of Neurology in 2015. In that study, they treated 23 people with clarithromycin, and they reported the results on 20 cases using clarithromycin 500 mg twice daily. They did not show changes in reaction time but did show subjective measures of sleepiness were significantly improved. People did get gastrointestinal side effects and changes in taste, so it was not well blinded, so it is a little hard to know exactly how to interpret that, but, nonetheless, this may be a helpful agent.

Flumazenil – has also been used at Emory. At the meeting, they presented their experience with 153 patients they treated between 2013 and early 2015. They administered flumazenil as sublingual lozenges or transcutaneous lotion. Overall, 63% of people felt flumazenil had helped their sleepiness, dropping the mean Epworth Sleepiness Score in the group from 15 to 10.3, and 39% of people remained on treatment at the end of the observation period, which was an average of 7.8 months. Interestingly, one of the predictors of clinical response was the presence of significant sleep inertia, with 72% of those with sleep inertia getting a good response versus 42% of those without sleep inertia.

Sodium oxybate (Xyrem) – is another treatment that was discussed for sleep inertia, which can be one of the most difficult symptoms to manage in people I see with hypersomnias. Whilst Xyrem is most commonly used in treating narcolepsy, Isabelle Arnulf from Paris has treated a number of people with IH with sodium oxybate. Their results, published in Sleep Medicine in 2016, showed that it can reduce morning sleep inertia and probably had a greater effect on this than on overall sleepiness symptoms.

JZP-110 – is a compound being developed by Jazz Pharmaceuticals that has both dopaminergic and noradrenergic activity. In two small clinical trials with a total of 126 subjects, it has been shown to increase the MSL on a Maintenance of Wakefulness Test by 8.9 minutes. This may not sound like much, but, in comparison, in the sentinel modafinil studies, MSL increased by 2.3 minutes, and, for dexamphetamine, there is a 5.6-minute change. So, at this stage, results for JZP-110 look promising, and it appears to be significantly more effective than modafinil or dexamphetamine. Larger phase 3 trials, aiming to enroll more than 800 subjects with sleepiness started in mid 2015, and results are expected at the end of 2016.

Non-drug treatments – There is increasing acknowledgement that medications only partially address symptoms of sleepiness and that there is a role for psychological and behavioural treatments to reduce the impact of symptoms in people with hypersomnias and other conditions that cause sleepiness. For people with narcolepsy with cataplexy, napping has long been used as a strategy, but for people with IH, napping as a strategy often doesn’t work, as they can’t have short naps and have significant sleep inertia on waking from naps. Research on behavioural strategies to help manage symptoms of sleepiness is now being undertaken, and I had a chance to talk with Assistant Professor Jason Ong about it at the meeting in the following interview: Sleep Talk: Episode 8 – Sleep 2016 Update.

Posted in: SomnusNooze

Leave a Comment: (0) →

Together, We Can Solve the Puzzle of Hypersomnia

Together, We Can Solve the Puzzle of Hypersomnia

Together, We Can Solve the Puzzle of Hypersomnia

What is a Patient-Powered Registry? Simply put, a patient registry is a collection—for one or more purposes—of standardized information about a group of patients who share a condition or experience. According to a publication from the Agency for Healthcare Research and Quality Research, "Patient-powered registries and patient-powered research networks offer new directions for patient-centered outcomes research, and contribute to translational science in important ways. Experts agree that these registries are transforming patient/caregiver support and advocacy groups into research organizations. They also provide patients and family members another way to become engaged in research beyond the role of advisor or informant to researcher-generated studies." In 2015, Dr. Michael Twery, Director of the National Center on Sleep Disorders Research at the National Institutes of Health, told the Hypersomnia Foundation that establishing a patient-powered  registry was the most important thing that we could do. Therefore, a group of volunteers, including Board members, CoRDS (Coordination of Rare Diseases at Sanford), and the Medical and Scientific Advisory Boards of the Hypersomnia Foundation spent the past two years developing questionnaires to collect standardized information from people who have been diagnosed with one of the central disorders of hypersomnolence: idiopathic hypersomnia, Kleine-Levin syndrome, or narcolepsy (type 1 or 2).   What is an IRB? The purpose of an Institutional Review Board (IRB) is to weigh the risks and benefits of participating in research and to protect the rights and welfare of the research participants. The IRB must review and approve all “research” that involves human participants before beginning the research. Only when the answer is to all of the following questions is “yes,” to all of the following questions, you are conducting research: Was information collected in a systematic manner (that is, according to a predetermined set of rules)? Will information be used to draw conclusions about a general principle or question?  Will the information be distributed beyond the immediate setting in which it was collected?

What is a Patient-Powered Registry?
Simply put, a patient registry is a collection—for one or more purposes—of standardized information about a group of patients who share a condition or experience. According to a publication from the Agency for Healthcare Research and Quality Research, “Patient-powered registries and patient-powered research networks offer new directions for patient-centered outcomes research, and contribute to translational science in important ways. Experts agree that these registries are transforming patient/caregiver support and advocacy groups into research organizations. They also provide patients and family members another way to become engaged in research beyond the role of advisor or informant to researcher-generated studies.”
In 2015, Dr. Michael Twery, Director of the National Center on Sleep Disorders Research at the National Institutes of Health, told the Hypersomnia Foundation that establishing a patient-powered  registry was the most important thing that we could do. Therefore, a group of volunteers, including Board members, CoRDS (Coordination of Rare Diseases at Sanford), and the Medical and Scientific Advisory Boards of the Hypersomnia Foundation spent the past two years developing questionnaires to collect standardized information from people who have been diagnosed with one of the central disorders of hypersomnolence: idiopathic hypersomnia, Kleine-Levin syndrome, or narcolepsy (type 1 or 2).  
What is an IRB?
The purpose of an Institutional Review Board (IRB) is to weigh the risks and benefits of participating in research and to protect the rights and welfare of the research participants. The IRB must review and approve all “research” that involves human participants before beginning the research. Only when the answer is to all of the following questions is “yes,” to all of the following questions, you are conducting research:
Was information collected in a systematic manner (that is, according to a predetermined set of rules)?
Will information be used to draw conclusions about a general principle or question? 
Will the information be distributed beyond the immediate setting in which it was collected?

Wouldn’t you like to do something to help solve the puzzle of hypersomnia? Well you can! Sharing information about your symptoms, your previous treatments, and your diagnostic journey as part of the Hypersomnia Registry at CoRDS (Coordination of Rare Diseases at Sanford) holds the key to solving this complicated puzzle called hypersomnia.

Anyone can gather information on the Internet through polls, questionnaires, or surveys, but, to publish their results in a medical journal, researchers can use only information that has been obtained in a very specific manner that incorporates legal informed consent and privacy regulations. Therefore, CoRDS has put many safeguards into place to ensure that researchers can use the information you provide.

The first step is called Institutional Review Board (IRB) approval. (Take a look at the side bar accompanying this article to learn more about IRBs). The IRB at Sanford Research approved not only the CoRDS registry questionnaire, but also the hypersomnia-specific questionnaire that is part of the registry. Any researchers who want to use the information in the registry also have to obtain a first approval from their own IRBs and then a second approval from the Sanford IRB.

The second step in safeguarding your information is informed consent. This means that, in the process of signing  up to participate in CoRDS, you are given a chance to read information about the registry and you then sign a form that indicates you understand what you are doing. You can sign this form either electronically, if you are filling out the questionnaires on line, or with a pen, if you are completing the paper version of the registry. If you have any questions, you can call or send an email to CoRDS before you sign the consent form.

Thirdly, the information you provide is kept strictly confidential. The questionnaires that you complete will never be associated with your name—a computer generates an ID number that is assigned to your identifiable information (name, address, etc.) and to your responses to the questionnaires. Your identifiable information is then kept in one database and your questionnaire responses, tagged only with the ID number, are in a separate database (this is called de-identified data). Once researchers receive approval to look at the registry or questionnaire responses, they will be given only the de-identified data. The Hypersomnia Foundation does not have access to any of the information at any time.

Your privacy is also protected even if you indicate on your questionnaire that you are willing to be contacted to participate in additional research projects. For example, researchers might contact CoRDS and tell them that they want to send an additional questionnaire to all participants who have a specific symptom, such as long sleep time (> 11 hours/24 hours). CoRDs personnel would then contact everyone in the registry who indicated that they sleep for more than 11 hours per day and would like to participate in additional studies. CoRDS would provide these people with the researchers’ contact information, and it would be up to the individual people whether they contact the researchers to participate in the additional research.

Participating in the Hypersomnia Foundation Registry at CoRDS is a simple way for you to take part in research into the causes and treatments of hypersomnia. When we all complete the questionnaires, researchers will be able to compare our answers with those of hundreds, if not thousands, of others. The researchers will then be able to detect patterns, identify common symptoms, better define the disorders, and gain insights into what treatments work and those that don’t.

If every person with hypersomnia completed these simple questionnaires, researchers would be able to perform a crucial first step in research: to map the natural history of the disorder. Later this year, the Food and Drug Administration will be accepting applications for up to $400,000 in funding per year over the next five years to conduct natural history studies in rare diseases. To be competitive in the grant process, hypersomnia researchers will need your help. They will need a large database of information on patients with idiopathic hypersomnia, KLS, and narcolepsy, all of which are rare diseases. This is the first of many reasons why your participation in the Hypersomnia Foundation Registry at CoRDS is so vital.

Becoming part of the registry is easy. Won’t you take an hour of your time to help solve the puzzle of hypersomnia? Simply go to http://www.sanfordresearch.org/cords/ and click on the ENROLL NOW button to become a part of the Hypersomnia Registry at CoRDS. And feel free to download the new CoRDS/Hypersomnia Registry logo and make it your photo on Facebook.

Posted in: SomnusNooze

Leave a Comment: (0) →

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

Leave a Comment: (0) →

The Blight on My Daughter’s Life

I gave birth to my daughter at 7:28 pm after 33 hours of labor. I was worn out, so I relinquished my baby to the care of the nurses within a couple hours to get some sleep. I didn’t see Cait again till 6:00 am. And, for the first year and a half of her life, if I put her down at 7:00 pm I knew I wouldn’t hear from her again till 8:00 the next morning. In retrospect, I wonder if it was an omen of what was to come.

Cait settled into normal sleep-wake patterns as a toddler. Toward the end of grade school, though, I remember that, if I took us out to dinner, she would invariably complain of being tired. I kept having to tell her not to lay her head on the table in restaurants.HPIM0292.JPG

Through her adolescence, I learned the hard way that it was best not to say anything to her early in the morning. “Not a morning person” was the understatement of the decade.

Cait completed her first bachelor’s degree on schedule and stayed on to get another BA and earn a teacher’s certificate, having settled on a career path late. It was during that program that the wheels came off. She lost motivation. Her sunny disposition disappeared. She earned the BA but couldn’t complete the certificate. After about 5 months living with a friend and making no headway with a job hunt, she moved in with her step-dad and me.

She landed a job. I thought she’d gotten her feet under her. But then she just tanked—spent all her time in bed except for when she had to work. It looked like depression to me. She found a counselor. Eventually she agreed to take antidepressants. Her mood lifted, but the fatigue didn’t go away. Her doctor checked her B-12 and her thyroid and screened for Lyme disease. She was sent for a sleep study and diagnosed with mild sleep apnea. She invested in a CPAP machine and used it faithfully. It didn’t help. She kept going back to the sleep study site asking why, and they would ask, “Do you meditate? Do you exercise? How much protein are you eating?”

Five months later, she thought she might have had a mini seizure. She was referred to a neurologist who happened to be a sleep specialist. The pre-appointment questionnaire drilled down on questions about sleep, and Cait answered them fervently. On her first visit, this doctor quickly resolved the question she came with and then said, “But I think you have another problem and it isn’t sleep apnea.” It was another month before a sleep study with MSLT confirmed it, but, when we did the Internet search that night, we knew he was right. Idiopathic Hypersomnia.

I hate this blight on my daughter’s life. I’m her alarm clock. I pack her lunch daily and make sure she has a good dinner every night. She doesn’t have energy for anything except her job. What kind of life is this? She’s planning now to move back to Illinois where she has a cadre of friends and a beloved church community within a 15-minute drive radius. I want her to have a life of her own, but I wonder, “Can she pull this off? Will she have the support she needs?” How I hate this blight on my daughter’s life!!

Ellen Swinford

Germantown, MD

Posted in: Awareness, idiopathic hypersomna, Journey, Share the Journey Stories

Leave a Comment: (0) →

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

Leave a Comment: (0) →
Page 5 of 14 «...34567...»