The Science of Sleep

drsolet masscfidspres and eventscomm for article This article is a summary of the lecture by Dr. Jo Solet, Harvard Medical School researcher and sleep expert, presented to the Massachusetts CFIDS/ME & FM Association (MassCFIDS) on April 6, 2013. The event was co-sponsored by the Massachusetts Department of Public Health and held at the Hinton State Laboratory Institute Auditorium in Jamaica Plain, MA.

Photo shows Charmian Proskauer, President of MassCFIDS (on far left) with Nancy Smith and Rita Sanderson, Events Committee Coordinator and Assistant Coordinator on either side of Dr. Jo Solet.

 See also related article: Tips for Sleep and Fatigue Management in CFIDS/ME & FM

 

 

 

 

 

 

 

 

 

 


Identifying interacting drives for sleep

Circadian and diurnal rhythms

Dr. Solet introduced her lecture with a picture of a lunar moth attracted to the light, explaining that the moth has evolved with diurnal rhythms (meaning day/night rhythms). She then displayed a picture of a store open 24 hours and used that as an example of how our changing lifestyle has wreaked havoc on our own diurnal rhythms. In the past, she explained how circadian rhythms were in sync with normal exposure; when it got dark outside, people would go to sleep.

Today, we live in a 24-hour society in which circadian rhythms can be undermined by artificial light and technology, which manifests as disrupted sleep patterns. Dr. Solet listed some of the culprits that we don’t even think about such as: electric lights on all the time, a culture of overwork, open 24/7 technology, insufficient exercise, a café on every corner where people can tank up to stay awake and can be tempted by treats that increase extra calories without realizing it, and the fact that people are limiting their sleep.

She raised the question “What are the drives that are being affected by our changing lifestyle, by this natural experiment we’ve undertaken, where we don’t have the normal exposure to light and balanced circadian rhythms?”

What regulates sleep/wakefulness

Wakefulness is regulated by two processes—Homeostatic and Circadian drives. The homeostatic drive for sleep and waking are neurobehavioral and physiological functions. The longer you are awake, the greater your homeostatic drive for sleep becomes.

The circadian drive, the night day light cycle, also drives sleep. Dr. Solet explained that when it is brighter, we are more alert. As an example, she used the case of someone staying up all night and perhaps at about 3 am getting really tired but then by 8 am getting a burst of energy, but by late afternoon the person wasn’t doing so well. It is just the overlap of circadian rhythms that causes that effect.

She presented a slide that had a graph of the circadian and homeostatic sleep timelines showing where they overlapped.

Individual differences/Chrono-types

In addition to the above processes, sleep is influenced by people’s inclination toward greater alertness in morning or evening; those two types are called Chrono-types. It is believed to be a biological proclivity that people are prone towards one or the other. People who stay up late are frequently called night owls, while those who get up very early are larks.


Understanding the elements of sleep architecture

Sleep cycles through the night

A hypnogram/sleep architecture chart that is color coded, showed the continuous sleep cycles. Each cycle lasts about 90 minutes.

Starting at the wakeful state, a person then goes into progressively deeper sleep known as Delta, then back up toward lighter sleep, closing the 90 minute cycle with REM (rapid eye movement, also called dream sleep).

The color coding shows that the duration of each stage varies as the cycles proceed during the night’s sleep, such that upon falling asleep, a person spends more of the 90 minute cycle in deep sleep, and by morning, much a greater proportion of time is spent in REM.

Dr. Solet mentioned that up until 1929, when the Electroenchephalogram (EEG) was invented, researchers thought when a person went to sleep, there was no brain activity and considered it a dead zone period.  With the results of the EEG, which measured the electrical activity of the brain, researchers discovered that the brain is very active during sleep and that challenged the thinking of the day. Scientists and researchers had to rethink what they thought they knew about sleep. 

What defines the sleep stages  

During sleep studies, the person’s brain is hooked up to an EEG and the brain-wave activity is measured. Each stage produces certain brain-wave activities that define the stage. Therefore, researchers can tell which stage of sleep the person is in by looking at the frequency and amplitude of the waves.

Need for sleep changes during development. A sufficient night of sleep for children should be around 10-12 hours. For adults, somewhere between 7.5 and 9.5 hours is good. Very few people are natural short sleepers. Many adults run on 5-6 hours of sleep and think this is not a problem. Most are really sleep-deficient and not operating at their best, especially if limited sleep has been a lasting behavior.

Muscle paralysis during dreams

Researchers are always studying sleep and there have been many discoveries. Most people, while dreaming, have muscle paralysis, which is normal and prevents people from acting on their dreams.

There are a few conditions that Dr. Solet did not elaborate on where people get up during the dream state. By depriving research subjects of sleep, researchers have learned about the important contributions of sleep and that different sleep stages may serve different restorative requirements.

Positive sleep effects

Sleep produces positive effects on memory, problem-solving and creativity, enhancing integration and extraction. There are many reported cases of a person wrestling with a problem and falling asleep and by morning, waking with a solution.

Research has shown that well-slept people are more likely to produce a creative answer to a problem than those who are not well-slept. Sleep has a consolidating effect and enhances learning.

Dr. Solet stated “It is most efficient to give some of your time to sleep.” Babies are sleeping 18 hours a day, half of which is spent in dream stage. As people get older, sleep changes and the quality of the sleep changes, with the proportion of deep sleep decreasing.


Common sleep terms and acronyms

Commonly used acronyms:

ES= Excessive sleepiness
TIB= Time In Bed
TST= Total Sleep Time
Sleep Efficiency= TST/TIB
Sleep Latency= Period before falling asleep
WASO= Wake After Sleep Onset
SWS= Slow Wave (deep) Sleep
REM= Rapid Eye Movement Sleep
Sleep Inertia= Post-wake “fog” before full alertness
PSG= Polysomnogram, measure brainwaves
Actigraphy= Sleep assessment through motion tracking wrist device
PMR= Progressive Muscle Relaxation


How sleep changes over one's lifetime

Changes in sleep with aging

Dr. Solet explained that with age, sleep becomes lighter with more night awakenings. Sleep latency is how long it takes you to fall asleep—this doesn’t change much with aging. CFS and FM patients complain that they have trouble falling asleep, so that they have increased sleep latency.

What does change in aging is WASO, and as age creeps up, waking becomes more frequent and then it is a question of how the person handles that and how they help themselves get back to sleep. REM only decreases somewhat with aging.

What changes the most dramatically is restorative sleep, the deepest sleep. The proportion of deep sleep lessens with age. Dr. Solet believes the secret to the fountain of youth could be in finding a way to increase this deep slow-wave sleep.

Sleep efficiency is defined as the proportion of Time in Bed (TIB) to Total Sleep Time (TST). Typically activity and morning light exposure are sleep enhancing, but if you stay in because you are ill, you are not getting either of those.

With CFS and FM patients, post-extertional malaise has to be considered and activity measured.

Adulthood effects on sleep

Dr. Solet showed a slide that presented some of the issues effecting sleep in adulthood. It listed the following:

•  Menstrual cycles can effect sleep efficiency
•  By the age of 20-30 years old, deep sleep diminishes by about half and continues to diminish with age
•  Self-care opportunities may decline
•  Family and work responsibilities peak
•  Incidence of sleep disorders increases
•  For women, hot flashes during menopause can disrupt sleep
•  Daily life structure can be lost with illness and/or retirement
•  TIB may increase while TST decreases
•  Physical activity and light exposure may become limited
•  Pain and medications may effect sleep


Sleeping patterns and sleeping conditions

Factors that influence sleep

Dr. Solet explained each of the following, and how it can play a role in sleep issues.

One of her examples was a college student living in a dormitory and how, if she is a morning person, she may have a problem if late night noise in the dorm doesn’t allow her to get to sleep. Some sleep influencing factors cannot be modified such as age, gender and genetics; others can.

Consistency in sleep schedule is helpful; the body actually needs that. The body used to be in sync with nature such that when the sun went down, you went to sleep. With today’s 24/7 cycle, there are no clear lines and a person has to create her own.

It is better to go to bed about the same time each night rather than a different time every night. Social jet lag is the term used to explain Monday morning fatigue for individuals who stay up late on the weekend and drag into work on Monday.

If you are sleeping with a bed partner who disrupts your sleep, or is on a different schedule, it may be better to sleep alone and have visits.

Pets should be trained not to disturb your sleep. It is better to have a pet sleep on the floor and not the bed with you. Many pet owners don’t even think about putting their pets out of their bedroom.

Many substances have effects on sleep. Caffeine is alerting and is sometimes used in combination with a short nap.

Doctors will use this technique where they drink a strong cup of coffee and take a twenty-minute nap. When they get up, the caffeine has taken hold and it acts as a stimulant alone with the rejuvenation from the nap. Caffeine can and does affect sleep and it is not a good idea to drink it especially after noon, except for emergencies.

The majority of CFS and FM patients may have alcohol intolerance and do not drink. Alcohol can initially be a sedative, but it decreases sleep duration and efficiency, suppresses REM, and increases WASO, especially in women.

Benadryl, an over-the-counter antihistamine, is sometimes used as a sedative because it can cause drowsiness, but it inhibits SWS and REM sleep, leading to non- restorative sleep, lasting sleep inertia, rapid tolerance, and rebound insomnia.

Some influences on sleep are under our control, but others are not. The following is a bullet list for a quick check:

• Exercise and activity levels
• Sleep schedule
• Bed partner and pets
• Caffeine, alcohol and medications
• Psychological state
• Sleep disorders
• Age/gender, genetics
• Cultural norms/lifestyle
• Light and circadian drive
• Sleep environment
• Sleep debt
• Sleep disorders

Influences on sleep chart

influencesonsleepchart


The risks of limited sleep

Epidemiological risks of insufficient sleep

In explaining the epidemiological evidence, Dr. Solet showed a slide that had a color-coded map of the United States showing the age-adjusted percentage of adults who reported 30 days of insufficient sleep or rest. Massachusetts has room for improvement.

There are two groups that are at special risk of being under-slept: the under-resourced who may be living in conditions beyond their control and the over-committed and ambitious who may take on more than is possible.

These maps from The Centers for Disease Control and Prevention (CDC) showed an intersection in epidemics in the states of the under-slept with a high incidence of diabetes and obesity. In discussing obesity, insufficient sleep causes the appetite to increase and the satiation level to drop,leading to overeating. When you’ve been up all night, you will be hungrier.

The people who have insufficient sleep will have a sleep debt. Just like having a credit card debt, the balance has to be paid off, in this case with sleep.

Study citation: Jeffrey S. Flier and Joel K. Elmquist, PhD “A Good Night's Sleep: Future Antidote to the Obesity Epidemic?”, Ann Intern Med. [editorial] 141, no. 11 (2004): 885-886. doi:10.7326/0003-4819-141-11-200412070-00014.

Physiological consequences of sleep debt

Leptin is a hormone that signals satiation. With insufficient sleep, Leptin levels drop and levels of ghrelin, which regulates appetite, increase. Ghrelin signals the body to turn on the hunger and fat store. This signals a negative energy balance, which in turn can increase hunger and lead to obesity.

People think if they are up for a longer period of time, they will burn off the extra calories, but research has proven them wrong. When tired, many head for the refrigerator rather than for bed. They gain weight.

There is also the possibility of immune cell activation and increased inflammation as well as irregularities in stress hormone regulation.

Dr. Solet made her point regarding food marketing practices by explaining how the recent analysis of portion sizes in cookbooks over the years shows increases and in general, how the food industry has supersized portions. The proliferation of fast food restaurants has contributed to the problem of obesity and grab and go eating.

Research from the CDC (Obesity data from CDC; Sleep data from Roffwarg in Science, 1966, National Sleep Foundation polls, and from Hale, Lauren in the Journal of Public Health, 2005) showed the increase of obesity from 1960 to 2000, while at the same time the chart showed mean hours of sleep have been dropping between 1960 to 2000. In 1960 the average sleep duration was 8.5 hours.

While the current average may be 7 hours, Dr. Solet said some research seems to indicate we may need closer to 9 hours of sleep.

Another chart showing how much sleep pro athletes get indicates they sleep more than most people do. They are paid to be in their best form, which supplies extra incentive to get enough sleep. The chart makes the point that we need more sleep to maximize our own capacities.

Studies cited: 1)  Roffwarg H.P. et al, “Ontogenetic Development of the Human Sleep-Dream Cycle,” Science 152, no. 3722 (1966): 604-619.           2)  Lauren Hale, “Who has time to sleep?” Journal of Public Health 27, no. 2 (2005): 205–211. doi:10.1093/pubmed/fdi004.

Altered memory and cognition

Restricted sleep impairs vigilance. Lack of sleep causes poor choices, impacts memory and cognition.

In a study (Van Dogen, Sleep, 2003) where the participants were rated on their vigilance after 8, 6 and 4 hours of sleep and then self-reported on how they thought they were doing, the 6 and 4-hour sleep-participants showed they thought they were doing better than their actual performance. They had no insight into the fact that their vigilance was so impaired.

When people are repeatedly awakened during the night, Dr. Solet explained many will not remember any details because the memory is not fully online during sleep. She made the point that just because you are in bed for eight hours doesn’t mean you sleep for eight hours.

Along with arousals during the night, there is the sleep latency factor—the amount of time needed to fall asleep. Another good example of the sleep-deprived are the doctors who have been up and on call for more than 24 hours and then get into a car to drive home.

A study in which Dr. Solet was a co-author, “Sleep Disruption due to Hospital Noises: A Prospective Evaluation”, found study subjects unable to accurately report how many times they had been awakened by noise during the night. However, Dr. Solet informed us this particular finding of not remembering accurately was not delineated in the findings because it was expected.

Study citation: Buxton O.M. et al, “Sleep Disruption due to Hospital Noises: A Prospective Evaluation”, Ann Intern Med. 157, no. 3 (2012): 170-179. doi:10.7326/0003-4819-156-12-201208070-00472. Author information: Orfeu M. Buxton, PhD, Jeffrey M. Ellenbogen, MD, Wei Wang, PhD, Andy Carballeira, BM, Shawn O'Connor, BS, Dan Cooper, BS, Ankit J. Gordhandas, SB, Scott M. McKinney, BA, Jo M. Solet, PhD.

Review of effects of insufficient sleep

• Impaired attention and reaction time
• Decreased memory and concentration
• Worse mood, depression
• Impaired task completion
• Psychosocial difficulties
• (Higher) Risk of injuries and falls
• (Higher) Incidence of pain and inflammation
• Weight gain
• Diabetes
• Cardiovascular disease
• Increased consumption of healthcare resources


Sleep changes commonly found in CFS and FM

Many CFS and FM patients report experiencing the above complaints and describe specific experiences with sleep. Disordered sleep has been studied in the general population and may shed light on mechanisms useful for improving the situation.

Subjective reports of sleep changes in CFS and FM patients
  - Difficulty falling asleep
  - Difficulty staying asleep
  - Un-refreshing sleep

Complaints by CFS and FM patients that MAY be related to disordered sleep and are elements of the CDC case definition of CFS
  - Post-exertional malaise
  - Fatigue interfering with functioning
  - Pain
  - Impaired short-term memory

Tools for studying sleep

  • PSG = Polysomnogram measures brainwaves EEG + EMG + EOG (Electro-ocular grams) and is done during a sleep study assessing brain wave activity, muscle activity and eye movement activity
  • Actigraphy = Sleep assessment through a motion-tracking wrist device, an accelerometer, which then can be put into an algorithm to interpret
  • Oximetry = Measurement of oxygen in the blood supply with a clip put onto the finger.
  • Video
  • Questionnaires = Self report of sleepiness, for example, have you fallen asleep watching TV or driving?
  • Diaries and Apps = Facilitate tracking activities and behaviors


Sleep research—challenges, findings, and future direction

Challenges in doing CFS and FM sleep research

Dr. Solet laid out a list of why doing sleep research especially with this patient population is difficult. Individuals must be found and be willing to sign on as study subjects.

Diagnostic categories can be difficult to define and the clinical criteria and severity can vary. Pooled data can obscure differences and standard scoring periods of 30 seconds in sleep studies may not detect changes in sleep micro-structure.

Adjustment to sleeping in the lab with equipment can be difficult, especially the first night. Subjects’ awareness that they will be videoed and watched can increase stress. Multiple nights of testing are expensive and stressful for subjects.

Primary sleep problems and other comorbid illnesses complicate conclusions. Dr. Solet said, “We tend to look for our lost keys under the street light because it is brighter there, but that doesn’t mean that’s where the keys are.” Her analogy made clear that although the medical professionals have the tools to study certain issues, patients don’t necessarily have a singular sleep issue to the exclusion of other issues.

Sleep changes in CFS and FM

Dr. Solet made the point that the research findings in studies are inconsistent, possibly due to the small number of people enrolled, a difference in study subjects, or that the study is so small it does not have the statistical power to be convincing.

Dr. Solet cited a study conducted by Melinda L. Jackson and Dorothy Bruck, “Sleep abnormalities in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A Review”, J Clin Sleep Med 8, no. 6 (Dec. 15, 2012): 719-728, http://dx.doi.org/10.5664/jcsm.2276 showing there were alterations in sleep stage transitions and sleep instability in CFS and FM, but not a basic deficit in sleep function.

Based on EEG and Polysomnogram tests, there have been some demonstration of changes in sleep architecture in CFS and FM patients with abnormal findings such as:

• Abnormal sleep stage transitions
• Disruption of duration and distribution patterns
• More arousals and lower sleep efficiency (Time in Bed)
• Alpha waves of 8-12 HZ (cycles per seconds) intrusion in 01-4 HZ Delta sleep, abnormal pattern during non-rem sleep on EEG. This means when in deep (Delta) stage sleep, the Alpha (REM) stage intrudes into the deep sleep and interrupts the deep sleep stage, which suggests you are not getting the true benefit of deep sleep. This can be associated with daytime sleepiness, pain and depression.

In ME/CFS patients:
  - Shorter Total Sleep Time (TST)
  - Shorter total Rapid Eye Movement (REM) and more REM to waking (waking up after dreams instead of moving into a deeper sleep)
  - Shorter spindles* called S1, S2, more S1 to waking
  - Extended sleep latency (prolonged sleep onset)

In FM patients:
  - Decreased spindles* in stage 2 sleep. Spindles are a sign of stage 2 sleep and decreased spindle density in stage 2 mechanisms shows impairment. Spindles come from the thalamus through to the cortex. Currently, researchers are looking into the genetics of spindles.
  - Individuals with FM who had the best sleep in the laboratory, when exposed to noises, in Dr. Solet’s research were those who had the most spindles in stage 2 sleep.

* A spindle is a burst of oscillatory brain activity during stage 2 sleep and consists of 12-14 HZ waves, which occurs for at least 0.5 seconds.

The importance of biomarkers in CFS and FM

Dr. Solet asked, “Why are we looking for biomarkers and what good will they be to us?” If real biomarkers could be identified, it would help improve diagnostic ability as well as the following:

• Help to understand the pathways and mechanisms going forward for patients
• Help to increase funding because it would confirm an organizational treatment direction
• Lead to interventions
• Validate subjective experiences

If biomarkers were identified and available, getting a diagnosis would be easier and reached more quickly; thus, there would be less suffering by the patients. Subjective reports by patients are too easily rejected in the absence of an objective biomarker and many times patients feel invisible.

Role of Heart Rate Variability in CFS

A study recently published in Autonomic Neuroscience that looked at Heart Rate Variability (HRV) in CFS is very promising in Dr. Solet’s opinion. Solet explained that HRV refers to the variation in the time interval between heartbeats (presentation slide New Direction: Heart Rate Variability).

This study found that the parasympathetic component—the “fight or flight” mechanism of the autonomic nervous system—was not functioning properly in CFS patients. Instead, it left patients in a more aroused state than should be the case.

The normal changes in heart rate adjustments are not happening and patients end up feeling “wired but tired.” This was a consistent finding and one that Solet views as being very hopeful because there may be ways to modify it, with neuro-feedback or pharmaceutical interventions.

Study citation: Fumiharu Togo and Benjamin H. Natelson, “Heart rate variability during sleep and subsequent sleepiness in patients with chronic fatigue syndrome,” Autonomic Neuroscience 176, no. 1-2 (March 14, 2013): 85-90. doi: 10.1016/j.autneu.2013.02.015.


Options for sleep management

How to create a sleep-conducive environment

Dr. Solet then spoke about what people can do to take control over the night and create a sleep- conducive environment. Start by evaluating your bedroom environment (e.g., sound, light, temperature, humidity, safety, and technology in the bedroom) and limiting your bedroom activities to sleep and sex only. The recommendations shown below are typically geared for the average person. However, Dr. Solet suggests individuals with CFS or FM try to incorporate those that are reasonable for their special circumstances.

Improving Sleep I

    • Condition yourself to move into a “wind down” routine
    • Use white noise from HEPA filters to help mask noise while cleaning air
    • Negotiate with other people in the house for quiet during the sleep time that you need
    • Use room darkening curtains to prevent bright light from waking you up
    • Keep the bedroom at a cool temperature and with adequate humidity
    • Clear the pathway around the bed from tripping hazards
    • Don’t use electronic devices close to bedtime or while in bed because the type of light they emit blocks melatonin which naturally rises at night
    • Use incandescent light or electronic reading devices that are not back-lit and won’t disrupt melatonin production if reading helps you relax at bedtime
    • Remove TV from the bedroom or put it on a shut off timer so it does not wake you up
    • Use the bedroom for sleep and sex only

 

Improving Sleep II

    • Go along with your chrono-type and respect your natural proclivities—your tendency towards morningness or eveningness
    • Make sure things that you use (e.g., prescriptions, over-the-counter medications, alcohol, substances, supplements, caffeine intake) are not causing side effects or negatively impacting your ability to fall asleep
    • Be mindful about exercise and light exposure—morning light is the most alerting and most beneficial in maintaining circadian entrainment
    • Do your best to maintain a consolidated sleep schedule (i.e., keeping your sleep periods together)
    • Try to get everything under control, like night care responsibilities of elderly parents, partners, children, and pets, before going to bed
    • Negotiate with your partner or other family members to deal with nighttime issues so you don’t have to disrupt your sleep

Improving Sleep III

    • Allow sufficient vertical time after dinner so that you are not going to bed with a full stomach If you have acid reflux, when in bed, elevate your head with a wedge pillow
    • Create a bedtime ritual, like reading or listening to music, but NOT looking at all your emails or other alerting activities when getting ready for bed
    • Taking a warm to hot bath two hours before going to bed, instead of a morning shower, has been found to benefit people with Fibromyalgia by cooling down their body temperature and promoting better sleep
    • Positioning in bed for restful sleep may include placing pillows to support or prop up painful areas and wearing comfortable clothing
    • Prepare for WASO (wake after sleep onset): have water by your bedside for thirst; keep the path clear to the bathroom and set up a small nightlight in case of nocturia; keep eye drops handy for dry eyes; and be prepared to use self-soothing routines to help yourself get back to sleep
    • If your problems with sleep are getting worse, despite all your efforts, then discuss the situation with your doctor and advocate for further screening; it is not uncommon to have multiple health problems and primary sleep disorders become more common with age

 

Additional tips and considerations  

Taking a power nap has many benefits for physical health and memory/concentration. Dr. Solet is a big fan of napping and mentioned advocating for rest areas in hospitals, hoping to create a setting for nurses, who often work 12-hour shifts, to take power naps. These can help to restore mental clarity and promote patient safety.

Short naps of 20-30 minutes, often referred to as “refresher” naps, can make a difference. She encourages these for everyone who can fit these into his/her schedule.

A full cycle nap takes 90 minutes and should be taken earlier in the day, so it does not interfere with the nighttime sleep schedule. Since full cycle naps bring people into deeper sleep, Dr. Solet advised the audience to allow enough time to get through sleep inertia by avoiding immediate activities that requiring high levels of attention until they are fully awake.

Another suggestion offered by Dr. Solet was to look at alternative paths, like meditation and yoga, to add restoration to one’s life. There is medical evidence that these techniques can contribute to neurogenesis and greater preservation of one’s nervous system.

Anticipate, recognize, adapt work-life balance

Dr. Solet concluded this segment with an emphasis on the importance of anticipating and making necessary preparations ahead of time, especially as individuals living with a chronic illness.

She stressed that learning to say a positive “no” can help create balance as part of a work/home/chronic illness strategy.

There may be times when you feel like you are driving on empty and if you are still working, it may be wise to seek advice about whether to disclose your disability/health problems and ask for reasonable accommodations under the protections of the Americans with Disabilities Act (e.g., to be permitted to take rest breaks at work which could help with job performance).

Social support is critical because it provides guidance and positive interaction with others.

Tools for self-awareness are also very important because they can help someone recognize/become aware of details or changes in her health. For example,
    • Using a sleep diary or journal, or even getting an app for the cell phone, can help one keep track of one’s sleep schedule to see patterns that might otherwise be missed.
    • Flexibility and pacing are techniques that help to maintain a healthy balance. Don’t be rigid with yourself. Try to be forgiving.
    • Recognize times when you are well enough to tackle difficult challenges and when it may be better to turn to something less demanding, like sorting the laundry.
    • Develop a contingency plan for things that you do which are important, in order to have an alternative arrangement for when you don’t feel well.
    • Remember, the power of “no” is a critical skill that everyone should learn—knowing how to say no can actually being respectful of yourself and the other person.


Sleep disorders

Overview of common sleep disorders

Next, Dr. Solet described common complaints that patients give and could be indicative of sleep disorders. Individuals may report they can’t fall asleep or can’t stay asleep; they are sleeping too much or at the wrong times; they are moving around during sleep or feel that they are not breathing right during sleep.

Untreated sleep disorders may explain and contribute to fatigue and must be carefully excluded. A summary of common sleep disorders may include:

- Insomnias or hypersomnias (i.e., can’t sleep or sleeping too much)
- Restless leg syndrome (RLS) and periodic limb movements disorder (PLMD)
- Sleep apnea: two types, one is associated with an obstruction of the respiratory system and the other, central apnea, is a neurological problem
- Parasomnia: sleep-walking, talking, bruxism
- REM sleep behavior disorder (i.e, acting out what the individual is dreaming)
- Psychiatric: depression/dysthymia, anxiety, post-traumatic stress disorder (PTSD)
- As mentioned earlier, the sleep environment including partners, pets, environmental disruptions should also be evaluated

Sleep screening considerations

  Life cycle stage—Different problems that people have with sleep, in part, relate to their life cycle and developmental stage: adolescence, pregnancy, menopause, and aging.
  Health Status—Check for other health problems that could impact sleep, like fatigue, pain, allergies, depression, anxiety, PTSD, diabetes, weight, and medications.
•  Special Stressors— Find out if the patient is going through a difficult situation (e.g., grief, job loss, relocation, divorce, or an existential crisis) that could affect sleep.
  Personal and family sleep history issues—Assess a patient’s heritage or family history, which may provide evidence of a predisposition for certain problems.
•  Sleep hygiene and habits—Ask patients about their exercise, eating, activities in bed, erratic schedule, caffeine and/or alcohol consumption.
•  Sleep environment—Review sleep setting/disturbances (e.g., partners, noise, light).
  History of accidents—Inquire about patient being drowsy while driving or having excessive daytime sleepiness, which may suggest sleep apnea or other sleep disorders.
  Sleep apnea—Evaluate for sleep apnea. There are two types: obstructive, which is associated with an obstruction of the respiratory system and central apnea, which is a neurological problem. Snoring, choking, and gasping during sleep are signposts of obstructive sleep apnea. Often, a sleep partner will report these problems while the patient might be unaware of their numerous arousals of interrupted breathing. Treatments may include the use of a CPAP machine, dental prosthesis, surgery to correct structural problems, and weight loss.
  Restless Legs Syndrome (RLS)—Tingly, abnormal sensations in the legs is indicative of RLS. It is found to be more prevalent in individuals of northern European heritage and to have an association with low iron reserves.
  Periodic Limb Movements Disorder (PMLD)—PMLD presents with movement of limbs during sleep.


Questions and Answers

Q: Do you know what the apnea-hypopnea index number needs to be before Medicare /Medicaid will consider it treatable?

A: I don’t know what number triggers insurance coverage. However, it depends on a number of things: who you see, your age, your symptoms, and additional problems you might have that could be exacerbated by the apnea. Young people who have a low index, 5-15, may not get treated, but as you get older, especially if you have low oxygenation, chances for treatment increase. Someone in the audience has that information for Medicare/Medicaid and it is 5 wake-ups per hour.

Q: Can you catch up on sleep on weekends?

A: It is better than not catching up but it is best to have a consistent schedule and that will make Monday mornings easier if you have to get up for work. It is best to have as little sleep debt as possible. If you let your sleep debt go for too long, it is possible you won’t be able to pay it off and it will cause physiological changes that may be difficult to reverse.

Q: How do you approach daytime hypersomnia?

A: It would be important to find out the cause of the daytime hypersomnia and rule out disorders like narcolepsy. Anyone who is really conking out during the day and sleeping at night needs a full sleep screening. It is also important that people do not assume that ongoing daytime sleepiness and conking out in a sitting position is typically part of CFS or FM. These could be signs of a separate sleep disorder or other medical problem.

Q: Why did you not mention use of medications for sleep problems?

A: I am not an MD and I don’t give out prescriptions. I think there are more hype and advertisements for sleeping medicines than is necessarily good for us. The data on the number of Americans who are self-medicating themselves to sleep and then again to stay wake and alert is alarming versus sleeping in a normal way. In CFS, if we can begin to unravel an indication of what is going wrong, we may be able to come up with a medication that enhances sleep, perhaps by increasing spindles in stage 2 sleep. It would need to be tested and proven. There are many risky, undesirable side effects of sleep medications such that they can induce a hypnotic like state of memory-loss during which a person can do activities such as eating, driving or walking around and not remember it. Individuals who cut their sleep short but use sleep medication, there is the potential that when they arise to go to work, they are not fully alert, but they are getting in their car and driving. Many of these medications are not benign, especially if you already have medical problems. The decision to use them should be made in a careful consultation with your doctor or even better, with a medical sleep specialist.

Q: Do most insurance plans allow for sleep studies?

A: This situation is evolving right now and some people think perhaps not in the best direction. In recent years, when there is reasonable justification for it based on symptoms and history, there has been support for in-lab testing. Testing would include a full polysomnogram and results would be read to look carefully at your sleep architecture and oxygenation during the night. These tests are very expensive and insurance companies have begun backing away from them and are asking people to do home studies. The home study equipment technology is advancing. One argument for home studies is if you’re testing someone in their own bed you’re testing the way they really sleep with whatever external interruptions: i.e. light, pets, sleep partner. If a home study is difficult to read or suggests more serious problems, you can ask your doctor to advocate for you to get a sleep study done in the lab.

Q: What would you recommend for someone who is wide-awake at 3 am?

A: A newspaper route. There is a belief in the U.S. that people are supposed to sleep uninterrupted for 8 hours. But in a natural setting, indigenous people have had what was known as a first sleep and a second sleep. They would wake up and share dreams, pour over their meaning, and then go back to sleep. So, if you wake up at 3 in the morning, it doesn’t mean something is wrong with you. The real question is if you wake up and haven’t had sufficient sleep, what kind of things can you do to put yourself back to sleep? There are calming methods such as breathing exercises, soothing music, etc. If you keep a sleep diary, it may help you see a pattern or figure out what works or doesn’t work to help you fall asleep. Dr. Solet’s concluding remarks, “I encourage you to be scientists.”


 

About Dr. Solet

Jo M. Solet, MS EdM, PhD, OTR/L is a Clinical Instructor in Medicine at Harvard Medical School, a member of the Harvard Medical School Division of Sleep Medicine and the Department of Medicine at Cambridge Health Alliance. She holds basic science, clinical, education, and research degrees; her HMS post-doctoral training was in behavioral medicine.

Dr. Solet is uniquely qualified to coordinate and contribute to interdisciplinary efforts. Bringing together evidence-based medicine with evidence-based design, she served as Principal Investigator for a multiple grant study of noise and patient sleep disruption in hospitals with the results published in the Annals of Internal Medicine.

She is a voting member of the Health Care Guidelines Revision Committee (HGRC) that develops construction guidelines for healthcare facilities that become law in the majority of the United States. She has also served as the elected Faculty Chair of the Harvard Medical School/Harvard School of Dental Medicine, Joint Committee on the Status of Women (JCSW), and on The Harvard University Task Force on Women in Science and Engineering. Dr. Solet is a science advisor to Lark Technologies, an MIT/Stanford start-up health technology company and has a small private practice near Harvard Square. More information about Dr. Solet’s research interests and publications is provided in For more information.


For more information

Learn more about Dr. Solet’s research interests and publications at the Division of Sleep Medicine, Harvard Medical School website: 
https://sleep.med.harvard.edu/people/faculty/899/Jo+M+Solet+MS+EdM+PhD+OTR+L

Dr. Solet recommends Sleep and Health Education, a resource provided by the Division of Sleep Medicine, Harvard Medical School:  http://healthysleep.med.harvard.edu/portal

Tips for living with ME/CFS and FM—in real life and online communities

Life for most patients diagnosed with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) or Fibromyalgia (FM) will become different from how it was prior to illness.

Different means that patients will have tested their limits and made changes to previous norms or expectations, to help them achieve a better quality of life.

While no one can completely escape negative or stressful situations, people with chronic illnesses may find that stress, pain and illness can become intertwined. Even getting through activities of daily living, an easy task for someone in good health, will usually pose a significant challenge for individuals with chronic illness.

So, it becomes essential that patients learn how to manage their time and energy as efficiently as they can, within the constraints of their illness. Patients will also need to examine and recalibrate their expectations.


Expectations

The first step is to determine which situations they can control or change from those they cannot; then, decide on how to best respond to these. Some things may be worth fighting for while others will need to be let go (e.g., much like the timeless message in the Serenity Prayer by Reinhold Niebuhr).

When it comes to expectations, patients need to consider the role of outside sources on their own expectations and personal assumptions, fears or beliefs which they themselves could be attaching to these. For instance, patients might be trying to live up to their pre-illness level or they might be doing more than they can realistically handle, for the sake of gaining approval.

It is important to remember that no one can be everything to everyone; people who push themselves and attempt to do this will only further jeopardize their health and self-esteem.

Realistic expectations are linked to time—the period of time when a patient tends to feel or function at their best. This window of time should be spent on high priority tasks or something meaningful to the patient—time is a precious commodity which needs to be used judiciously.


Making livable choices

Initially, patients may be quite concerned about their public persona, especially while they are learning to adjust to life with a chronic illness. They may struggle to redefine themselves because many were recognized primarily for their line of work—now what?

Therapists who coach people with chronic illnesses advise that patients make livable choices, seek a healthy medium and avoid going to extremes, like longing for ideal health or viewing themselves as hopelessly ill.

It is understandable that someone's situation can become very discouraging and when that happens, professional counseling or intervention could be very helpful. The choices that patients make will most likely be reviewed and readjusted to accommodate changes in the illness.


Growing beyond the illness

Another word of caution to patients has to do with patient's dependence on others. There is absolutely nothing wrong with asking for help with things that a person can no longer do and the amount of help needed will depend on the severity of the patient's condition.

On the other hand, relying on others too much may impose more limits and restrictions on the patient. Sefra Kobrin Pitzele, now deceased, wrote about dependence in her first book, We Are Not Alone: Learning to Live with Chronic Illness (Workman Publishing Company; 1st edition (January 9, 1986)), "If we allow it [dependence] to happen, we can let our spouse and children and parents and friends put us into a very small box in their minds and hearts—the box they reserve for pity. Sooner or later, we all want more love and respect than that. To get it, we must grow beyond our illness and relearn how to live with risks, anger, discomfort, challenges and everything else in life."

Ms. Pitzele used her own experiences (as a person living with lupus) to teach others with chronic illness how they could redesign their lives, so they could live them better. She encouraged patients to take pride in things they could still do and discouraged them from making excuses, getting angry or feeling apologetic about things they could no longer do.


Pick your battles

Nowadays, many people don't think twice about making snap judgments or remarks that are inappropriate or impolite—sometimes, even compliments are meted out without discretion or understanding.

There is a difference between telling someone that they look nice today or they are glad to see them and putting undue emphasis on "but you look so great" or "you don't look sick." It may be easier and better to overlook these sorts of remarks from strangers, by chalking it up to their ignorance or ill manners; however, people who are closer to a patient might do the same thing.

Anyone who bears the burden of illness on a daily basis will need to pick their battles wisely and not feed more energy or emotions into situations than they warrant. A simple honest reply may do, or using a little humor or creating a couple of clever quips can help patients end the situation in a way that can also let the other person know they made a faux pas.


When others cross the line

But there will be times when what is said by another person will be unacceptable, totally unfair or inaccurate—these should be addressed, to the best of the patient's ability.

People who are ill will typically become flabbergasted by these unexpected remarks and many won't be able to say anything on the spur of the moment. Depending on the individual, this can be turned into an opportunity to educate the other person, by responding in an honest and unapologetic way that speaks to the heart of the matter.

If the other person still does not get it, then it would be reasonable for the patient to remove themselves. Sometimes the other person could be someone's doctor whose remarks or conduct was very dismissive or in some way, offensive.

One option is to send a letter to the doctor about the incident after the patient has had a chance to quietly digest and reflect over the details of the incident. [But the patient shuld be aware that the letter will be made part of his/her record.]

The worst thing that patients or anyone can do is to respond by lashing out with their offensive remarks and/or stooping to the level of the offender.


Unspoken etiquette on social media

Since many people with chronic illnesses are involved in various online communities, it is important to address the need to be internet savvy. The internet is a wonderful resource for information, support, one's leisure and entertainment.

Social media allows housebound people to stay in touch with friends and family, but few might be aware of the "unspoken etiquette", especially on places like Facebook. Take parents, for example, who might be accepted as "friends" by their adult children on Facebook and assume this is a "warm welcome" for ongoing interaction with their kids on Facebook; well, it really is not (in most cases).

Adult children want to maintain their privacy, even on a social networking site, and use it as a place to primarily "hang out" with their peers. They won't be too thrilled to have their comings and goings be followed and "liked" by their parents.

Some things are implicitly viewed as being taboo, which include too many comments being posted by the parents on their kids' Facebook wall; clicking too often on the "like" button (which leaves the impression that Mom or Dad are watching their activity a bit too closely); "tagging" their adult children (or anyone else, for that matter) in photos without permission; and posting private family plans, news or other information on Facebook.

These features, "like", "tagging" and "share" are just some of the built-in tools on Facebook, which actually help to broadcast and/or further circulate a post or picture—in other words, these highlight activity on timelines, profiles, and in news feeds by the links that are automatically created and travel with the post or image.

When one stops and thinks about it, Facebook provides a window into the lives of adult children, relatives, friends, neighbors and other people which, in real life, does not readily exist. How much does it really matter to know what one's friends or neighbors are having for supper?


Leaving digital footprints

Some other things to consider is the amount of time spent in online communities, social media sites, or playing games. Whenever someone posts a comment or photo online, they may be hit with a slew of responses.

A lot of time can slip away, looking at the feedback and keeping the virtual dialogue going. It might be a good idea to monitor this and determine if some of this time should go to more essential things. Patients might also consider taking a social media sabbatical every couple of weeks.

People tend to be less reserved in what they blurt out on the internet than what they might say in person and this also applies to patients.

What one does online, stays online!

Social media is not a good place to vent one's personal issues, to post ongoing complaints or frantic comments, and to reveal too much information. Everyone's internet activity leaves digital footprints and a trail that others can easily follow, track someone's activity or interests, and/or end up in unknown destinations.

For instance, when someone "likes" a product or a business, the web browser will send information about that person's visit to a website. That person becomes automatically linked to that site and they might be displayed on that site or in their news feed.

People may not realize how a click here and there, has the potential of making them quite visible and getting targeted for a lot of unsolicited ads.

Overall, social media, message boards and blogs are "good things" providing people use these with a basic understanding of how things work as well as discretion and moderation.

IACFS/ME Conference 2014 Summary - Rosamund Vallings

by Rosamund Vallings MB BS
March 20-23rd, 2014

The day before the main scientific conference there was a joint session with those attending the patient conference, followed by professional workshops. There was a brief introduction by Prof Jose Montoya (Stanford, USA) when he emphasized the importance of a multidisciplinary approach to the illness and complimented the Chronic Fatigue Initiative on their collaborative approach. Focus should be on clinical and translational research using strict methodology.


Dr. Lipkin and the search for microbes in CFS/ME

Prof Ian Lipkin (New York, USA) was the special guest speaker and his talk was entitled “Small Game Hunting”. He said they were still able to use the earlier XMRV samples. He explained how one started with a hunt for “possible” microbes and then moved onto the “probable” when one could consider treatment options, followed by the “confirmed” when one looked at drugs and vaccines.

He told us how emerging diseases usually came from animal sources. He explained how micro-array techniques moved onto unbiased sequencing. There are 24 million peptide micro-arrays needed to investigate the vertebrate organism. He discussed as an example Kawasaki Disease, an autoimmune condition in children. Often diseases are due to an immunological response to an environmental trigger.

He then went on to discuss the human microbiome—abnormalities of which can create gastrointestinal symptoms, which in children are sometimes predictors for autism. He is interested in this relation to autism. There maybe reduced enzyme and transporter RNA. The organism suterella is increased in autism and there may be an antibiotic cause, and a lack of the gene affecting gastrointestinal metabolism.

He then talked about his involvement with the Chronic Fatigue Initiative, who are doing multiplex assays. He is working closely with Montoya looking at viruses. HHV-6 has been found in the plasma of 4 out of 6 cases. Looking for HHV-6 in PBMCs, 13% were positive in patients and 11% positive in controls. Annellovirus was found in 75% of the samples—this may not be useful, but negative findings are as important as positive.

Looking immunologically at CFS/ME, IL-17 was elevated in the first 3 years and then decreased. Lower levels were found in the CFS/ME patients’ cerebrospinal fluid. They are doing RNA sequencing looking at biomarkers in 100 cases compared to 100 controls. This equates to 117million reads divided into 3 “libraries”. But there is a need to control for library effects, as the “library” construction reflected the results—i.e., processing may be different.

They are also looking for chemicals produced by bacteria which may have systemic effects. He confirmed that there was zero evidence now for XMRV. Contamination is always a problem and contaminants must be eliminated prior to any analysis.

Eight professional workshops were then held throughout the first day. I attended the immunology workshop outlined below.


How do we recognize autoimmune disease?

The main scientific conference opened with the plenary address by Dr Noel Rose (Johns Hopkins, USA) with his discussion on how we recognize auto-immune disease. The main complaint in all autoimmune diseases is fatigue. Autoimmunity is an immune response to the normal antigens of the host.

Autoimmune disease is disease caused or significantly promoted by autoimmunity—with production of self-reactive T and B-cells. We are in fact developing lymphocytes and are “auto-immune” all the time, but we have mechanisms which recognize and control them. Disease occurs as a result of an uncontrolled response. Having antibodies is normal and not “disease”. A cause of disease by autoimmunity is hard to prove, but may be promoted by existing disease or make it worse.

There is prevalence of 80 diseases affecting every organ system. These diseases are among the 10 leading causes of death in women under 65. These diseases equate to up to 23 million people in the USA. They are diseases which share common features, are expensive and lifelong, and for which there are no cures. They are diseases which are on the rise. Systems affected most commonly include blood, connective tissue, endocrine, neuroloic, gastrointestinal, skin, kidneys and heart.

Evidence for autoimmune disease includes:

  • Direct transmission—e.g., via serum or maternal/foetal (lupus).
  • Indirect transmission when the antigen is defined and introduced to replicate the disease using animal models.
  • Circumstantial—no evidence of causation, but much evidence of disease—e.g., auto-antibodies, clustering, sex bias (75% female), HLA association, response to immunosuppression.

Some diseases look autoimmune but there is no evidence of self-reactive T-cells. They are more likely “auto-inflammatory” (caused by an innate immune response).

Factors leading to autoimmune disease

A combination of genetic predisposition, environmental factors and endocrine effect lead to autoimmune disease.

Genetic predisposition includes:

  • Evidence from family history. There may be evidence of multiple autoimmune diseases in a family. There is 30% identical twin concordance.
  • Major histocompatibility complex
  • Immunoregulatory genes. There are gene changes due to insertion of methyl groups etc. leading to changes in CD4, T-cell and B-cell changes.

Environmental factors include:

  • Viruses (e.g., EBV and MS), bacteria (e.g., B haem strep and rheumatic fever)
  • Food (e.g., iodine and its effect on the thyroid)
  • Pollutants (e.g., mercury)

Other effects include:

  • Hormones
  • Stress
  • Drugs

Pregnancy has a profound effect on autoimmune disease—some types become better, some worse.

We should use autoantibody presence in the blood with caution. This is NOT proof of autoimmune disease. Autoimmune diseases develop very slowly and a patient may have multiple antibodies over time.

The main conference papers were then presented, and the first session covered the latest research in immunology.


Immunology

Allergy-related immune signatures and duration of CFS/ME

Susan Levine (Columbia, USA) discussed allergy-related immune signatures and the duration of illness in CFS/ME. She discussed the importance of allergy mediators and links between IL-4 and IL-13 (both produced by TH-2 cells), and IL-17 produced by TH-17 cells, IL-10 produced by CD4 TH-2 cells and eoxtaxin produced in asthmatics.

For her study, she divided patients into groups with recent and longer lasting illness (less than or greater than 3 years). Unique immune signatures were found in short duration patients. Higher levels of cytokines associated with the allergic response were found in short duration patients compared to the longer duration patients. A TH-2 shift was supported. She stressed the need for future studies to include measures of histamine levels, total and specific IgE, prostaglandin E2, tryptophan and serotonin.

Plasma cytokines and exercise in CFS/ME

Ludovic Giloteaux (New York, USA) reported on his study of plasma cytokines in patients before and after a cardiopulmonary exercise test. Tests were done 24 hours apart. Baseline VO2-max was compared with healthy controls. There was a significant difference. The difference was also more significant after the 2nd test. Cytokines were measured at baseline and after exercise. There were no significant differences in cytokines between CFS/ME and healthy controls, but the chemokine IP-10 decreased significantly after exercise in the CFS/ME group. Results implied an abnormal immune response with immune suppression.

NK-cell degranulated related to release of lytic proteins?

Tellah Huth (Gold Coast, Australia) presented on Natural Killer (NK) cell degranulation and lytic proteins in CFS/ME. She looked at 2 natural killer cells: CD-56 and CD-16, both involved in cytotoxic lysis. She explained how granzymes and perforin are involved in the secretory pathway to the target cell. In CFS/ME there is significant reduction in Granzyme B, which when elevated inhibits the pathogenic activation signals. When down, there is delayed target cell apoptosis. Her results showed decrease in Granzyme B is CFS/ME patients. This may contribute to reduced NK-cell activity seen in CFS/ME. Further studies are needed to determine if there is a link between dysfunctional NK cell degranulation and release of lytic proteins.

Shorter telomere lenght in CFS/ME

Mangalathu Rajeevan (Atlanta, USA) then discussed a genome-wide analysis of differential methylation associated with CFS/ME. His results concluded that this differentiation was identified in CFS/ME, but only TERT was correlated with a corresponding change in gene expression. There was decreased methylation in CFS/ME, and increased expression of TERT, with shorter telomere length. Telomeres (the ends of chromosomes) are shorter in CFS/ME than in controls. Short telomeres are a marker for aging.


Virology

Chronic pelvic pain and enterovirus infection of ovarian tubes

This session started with a presentation by John Chia (Lomita, USA). His study was looking to see if chronic pelvic pain in ME/CFS patients was associated with chronic enterovirus infection of the ovarian tubes. Chronic pelvic pain has to have been present for at least 6 months and not necessarily associated with menstruation before a diagnosis is made. Enterovirus VP-1 (enteroviral protein) was found in the tubes of most patients with ME/CFS, but not in controls. Furthermore, injection of the lysate into SCID mice caused infection. Enterovirus was also detected in the vaginal secretions of 2 women. It should be noted that as the egg travels down the tube, there is a possibility of vertical transmission.

Human parvo-virus B-19

Human parvo-virus B-19 was discussed by Santa Rasa (Riga, Latvia) in relation to typical symptoms and markers in ME/CFS. Patients who have suffered infection with this virus can end up with the characteristic symptoms for a diagnosis of ME/CFS. A large study of 190 patients compared to controls was reviewed, and B-19 genomic sequence was detected more frequently (41/190) in the patients’ DNA isolated from plasma (a marker for active infection) than from whole blood (15/190) (a marker for latent infection), and this was more frequent than in controls. Most symptoms were slightly less frequent in the patients in the latent phase of their illness, apart from muscle and joint pain, which was worse in the latent group. Activation and reactivation of this virus may be a risk factor for ME/CFS. It should be noted, too, that there was increased incidence of infertility.

Chronic enterovirus infection of the stomach tissues

John Chia (Lomita, USA) then spoke again about the pathogenesis of chronic enterovirus infection in ME/CFS looking at stomach tissues. Patients with enterovirus in the gastro-intestinal tract usually have functional dyspepsia, and irritable bowel symptoms in the lower G.I. tract. 82% and 63% of the stomach biopsies stained positive for VP-1 and dsRNA respectively (significantly higher than controls). 24 mice were injected with the VP-1+,RNA+ stomach biopsies , and 66% of their spleen biopsies tested positive for VP-1. Other organs were also involved. Only one control specimen tested positive.Enteroviral dsRNA was frequently demonstrated in the stomach biopsies, and as it may play a central role in pathogenesis, it should be targeted for anti-viral therapy. (It was noted that there are over 150 enteroviruses and the Chia lab can only test for 11.)


Treatment studies

Orthostatic intolerance and midodrine

Treatment of Orthostatic Intolerance (O.I) using midodrine was addressed by Nicole Baldwin (Salt Lake City, USA). She described O.I. as treatable with midodrine and there are 2 FDA trials happening. Hours of vertical activity (HVA) was used as a measure to assess effectiveness. A pilot study of 23 patients was undertaken, but 12 never started the medication, 5 did not continue (lack of compliance) and 6 ended up taking it at the full therapeutic dose (10mg 3-4 hourly during hours of being upright). Those taking the full dose showed a small but meaningfully useful increase in HVA. Those who continued the medication tended to be those who were worse at baseline. There were improved symptom scores particularly for headaches. Lack of compliance was due to side effects and rebound effects. The drug has a short half life, so frequent dosing is needed. The benefits were small but significant and outweighed the side effects.

Effect of Baduanjin qigong exercises on fatigue

A presentation then followed by Tian-fang Wang (Beijing, China)—the first time we had had attendees from mainland China. She talked about the intervention effect of Baduanjin on the fatigue state in fatigue-predominant sub-health. Baduanjin is a set of qigong exercises. She showed a video to begin with to demonstrate the technique. The exercises were very gentle and simple, and were undertaken for 2 periods of 15 minutes each day. 129 subjects were assessed (62 in the treatment group and 52 controls). Symptom scores declined significantly in the treated group.

Isometric yoga

Takakazu Oka (Kyushu, Japan) then discussed the use of isometric yoga in CFS/ME. The technique consists of 6 slow and simple poses with associated breathing exercises. It is done in a sitting position (mainly because space is very limited in the hospital.) The study had to be designed to avoid post-exertional malaise, bearing in mind also that these patients are deconditioned. The technique also needed to be “mentally” simple. The exercises lasted 20 minutes, and the study was done over 8 weeks. Of the 24 patients studied (in 2 groups—one using yoga and one with conventional pharmacotherapy), one yoga patient complained of dizziness. No one’s fatigue was exacerbated by the yoga. All said their bodies became lighter and warmer and severity of pain decreased. DHEA-S increased and prolactin levels decreased significantly in the yoga group.

Home-based self-management for severe ME/CFS

Fred Friedberg (New York, USA) spoke of the results of a randomized trial looking at home-based self-management for severe CFS/ME. The 137 patients studied were mostly disabled and unemployed. They were assigned to 3 categories: 1. Wait list, 2. Home self-management using web diaries and activity monitors and 3. Home self management using paper diaries and step counters. Fatigue, functioning and depression improved in both of the 2 self management strategies, compared to wait-list controls, and were not significantly different from each other. There is therefore a role for home self management activities in generating improved outcomes.


Chronic Fatigue Initiative

Over lunch on that day, we had a group presentation from the Chronic Fatigue Initiative (CFI). This was introduced by Scott Carlsson. Several sites are involved and with a strong group of research scientists and clinicians. Nancy Klimas talked about the already 200 strong patient database with 200 controls for obtaining biosamples. A detailed assessment is done and there will be a biorepository for blood, urine, tears, saliva and rectal swabs. Very sick debilitated patients are included. Already it is evident that acute onset patients have a higher level of inflammatory symptoms. Females are more severely ill than males.

Gail Ironson talked about subgrouping with 4000 variables giving 18 factors associated with the main sets of symptoms. Symptom sets include: fatigue, neuroinflammation, gastrointestinal, FM, POTS, hyperlipidaemia, hypertensive, fever, NMH, increased weight. Other factors include: age/total cholesterol ratio, stress, unsteadiness/dizziness, past infection, asthma, abnormal potassium, no evidence of recent infection, hypothyroidism.

Dana March discussed clinical epidemiological aspects and the aims of the study. There are 4 main sites. They need 1000 completed surveys. They will look at changes over time. 60% patients are of sudden onset. Fibromyalgia is the commonest co-morbid condition. Deaths have been reviewed and so far cancers account for 37.8%, heart disease for 18.9% and suicide for 18.9%. Rate of cancer is higher than norms. Helpful treatments include: self-help 65%, traditional medicine 53% and alternative medicine 17%.

Mady Hornig is involved in pathogen discovery. She is collecting faecal samples to look at the microbiome. Repeat immunological profiling will be used for longitudinal analysis. She will be looking at spinal fluid etc.

Overall future directions of the CFI will include: metabolomics, proteomics, the entire microbiome, sequencing PBMCs and longitudinal analysis of immune signatures.

Tony Komaroff summarized this meeting by saying collection of data is 85% of the “sweat” and analysis about 15%. He reiterated how in such a short period of time, so much has already been achieved.

The afternoon session was interactive with case presentations by Drs C Lapp, L Bateman, R Vallings and D Peterson, chaired by Dr Klimas.


Case definitions

Leonard Jason (Chicago, USA) led this discussion and compared the various case definitons and their evolution over the past 25 years. The main variation in the definitions is the number of symptoms required for making a diagnosis. Case definitions that do not require the cardinal symptoms may not accurately identify the illness. However defintions requiring larger numbers of symptoms may include more psychiatric morbidity. Current consensus based definitions may lack construct validity, resulting in inaccurate diagnosis of CFS/ME.

A study to determine whether immunological, physical and social functioning varies in CFS/ME was presented by Sharni Hardcastle, (Gold Coast, Australia). Findings suggest that the ICC case definition [Canadian] identifies a group within the 1994 Fukuda defined patients with more severe impairment to their physical and social functioning. The ICC may also be more effective at identifying differences in the immune system found in CFS/ME. The presence of immune abnormalities combined with clear clinical measures could potentially serve as an important diagnostic tool in this illness.

Leonard Jason (Chicago, USA) then looked at diagnostic and criterion issues. Studies included looking at the prevalence of chronic fatigue in the general population. In order to progress the search for biologic markers and effective treatments, essential features of the illness might be empirically identified, so that individuals included in samples have the same underlying illness. Advanced statistical techniques, such as data mining are promising methods for identifying these features.


Public health research

Differential diagnosis between CFS/ME and fatiguing illness

Nicolette Carlo-Stella (Pavia, Italy) looked at the differential diagnosis of CFS/ME and fatiguing illnesses from a community-based sample. 89 patients were self referred complaining of post-exertional neuro-immune exhaustion to a specialized CFS/ME clinic. 40% of them were diagnosed as suffering from CFS/ME while 60% were not. The non-CFS/ME patients were suffering from a variety of illnesses: rheumatological 43%, endocrine 4.6%, psychiatric 5.6%, gastrointestinal 4.5%, haematological cancer 2.3% and bladder cancer 1.1%. Caution is therefor warranted before making a final diagnosis of CFS/ME.

Increasing the knowledge of physicians

Increasing medical knowledge about CFS/ME and related diseases was addressed by Tina Tidmore (Alabama, USA). The aim was also to set up a speciality centre. A local politician showed interest as he had a personal interest in Lyme disease. As a result a CME course was set up for medical professionals. The new Primer for clinicians was distributed. Further CME on Fibromyalgia and Tick-borne diseases was planned. Efforts continue to recruit physicians to run a specialized clinic. The long time needed for patient visits can be a barrier, as insurance companies do not re-imburse. First steps in creating a centre are to attract a physician willing to work in this somewhat difficult area.

Family aggregation studies in Spain

Family aggregation studies in CFS/ME were discussed by Jesus Castro-Marrero (Barcelona, Spain). The objective of their study was to know the family history and familial aggregation of Spanish CFS/ME patients. 1140 CFS/ME patients were included in the DNA databank. 36% patients had first degree relatives with CFS/ME and/or related conditions, such as fibromyalgia, immune-mediated diseases or rheumatological conditions.

UK CFS/ME biobank

Eliana Laerdo and Erinna Bowman (London, UK) talked about 2 years’ experience with the UK CFS/ME biobank. This is based at the London School of Hygiene and Tropical Medicine. They first discussed how the lay-scientific partnership had shaped and developed the biobank. A consultation process involved discussion between those with CFS/ME and carers, clinicians, researchers and experts in the field of human tissue banks. Those with CFS/ME were overwhelmingly willing to contribute with blood donations. A robust protocol has been developed. Samples are collected from patients with CFS/ME and controls (without fatigue or with MS). Several diagnostic criteria are being used to provide comparison. Regular follow-ups are planned. Blood samples need to be collected and processed within 6 hours. The biobank infrastructure and procedures were presented. The samples will provide an open resource for research, with the potential to lead to biomarker discovery and work that could translate into treatment. Collaboration with other international biobanks is planned.

Epidemiological study in Canada

Margaret Parlor (Ontario, Canada) presented the results quantifying and interpreting a broad range of health characteristics associated with CFS/ME, FM, and Environmental Sensitivities (ES)/MCS. This was to support health care planning in the area. Results were taken from the 2005 and 2010 Canadian Community Health Study (CCHS). 411,500 Canadians have been diagnosed with CFS/ME, 439,000 with FM and 800,500 with ES/MCS. This equates to a prevalence of 4.9% in 2010, which had increased from 4.2% in 2005. These illnesses were shown to have significant impact on individuals and families with many unmet healthcare needs. The information has been forwarded to health system planners, along with clinical and academic information.

Remissions in CFS/ME 

The group headed by Dana March (New York, USA) determined the natural course of CFS/ME in a multi-site epidemiology study, compared to other studies undertaken. 4 clinical sites were chosen and patients had had to have been in treatment for at least 5 years. The study was conducted by telephone interview by trained interviewers. The survey comprised mainly middle aged educated white women, born in the USA. Approximately 1/3 had experienced at least one remission. Viral type symptoms showed the most improvement over time. Many reported co-morbid conditions such as FM, depression, anxiety and hypothyroidism. Relatively few were engaged in work, school or equivalent activity. There was some variation across sites. The odds for permanent remission seemed low.

Treatments patients find effective

Lucinda Bateman (Salt Lake City, USA) examined the types of treatment which alter the course of CFS/ME in another similar multi-site epidemiology study. The most effective treatments were self-help strategies (65.2%) such as rest, diet and exercise, followed by traditional medicine (53.3%) such as prescription drugs and vitamins. A small percentage reported benefits from alternative/complementary medicine (16.9%) such as herbal remedies, massage, acupuncture. There was variation between sites.

Consequent conditions to CFS/ME and cancer prevalance

The prevalence of CFS/ME and co-morbid and consequent conditions was examined by Salima Darakjy (New York, USA). 84% of the CFS/ME patients reported at least one significant diagnosis after CFS/ME onset. These included FM, depression, anxiety and hypothyroidism. 16.4% reported malignancies, which is 4 times the prevalence in the normal adult US population. Further research is warranted looking at whether some CFS/ME patients are most at risk of cancers particularly in relation to shared pathophysiological mechanisms.


Provocation studies

Aerobic exercise testing

Betsy Keller (New York, USA) talked about the superior ability of a 2-day CPET (cardiopulmonary exercise test) protocol to detect functional impairment in ME/CFS compared to either a single CPET, submaximal exercise test or a VO2 prediction equation. The single CPET failed to identify functional impairment in 20% patients, and diminished functional capacity due to post-exertional malaise (PEM) could not be detected, yet occurred in 55% of subjects. Two serial CPET tests however did identify functional impairment in 98% subjects. Submaximal exercise tests were poor predictors of VO2-max in CFS/ME as was using the predicted VO2 equation. The results demonstrated the superiority of using two serial CPETs to delineate functional impairment in CFS/ME.

J Mark Van Ness (Stockton, USA) showed diminished pulmonary ventilation in CFS/ME patients during graded exercise tests. He postulated that this could be due to deconditioning. A second study showed that post-exertional effects seem to reduce the ventilator response further in CF/MES. These effects may be due to diminished ventilator muscle function during PEM or reduced ventilator neural “drive”.

Mitochondrial dysfunction

David Patrick (Vancouver, Canada) addressed the issue of whether screening for mitochondrial dysfunction and other metabolic disorders was important in CFS/ME. CPET often leads to symptom flare, and so alternative approaches were discussed. Changes in haemoglobin and oxyhaemoglobin in wrist extensors using grip tests were measured. Response to the test was compared between cases and controls by calculating the area under the curve of HHb over time. Submaximal exercise procedure did not distinguish between cases and controls, but HHb levels did vary between the cases and a subset of 19% met criteria that prompted further testing for mitochondrial disease. 3 cases had particularly low levels of HHb and 2 had adverse physical reactions. There was a greater level of self-assessed exertion in the ME/CFS group. Even submaximal testing was intolerable for a subset of ME/CFS patients and we should be mindful of using exercise for testing or treatment.

Oxygen extraction and lactate were found to be low in patients assessed by Ruud Vermeulen (Amsterdam, Holland). This would indicate a metabolic cause for exercise intolerance in the majority of 178 women with CFS/ME studied. The low lactate after exercise in the majority of these patients suggests that physical impairment in this group is caused by downregulation of carbohydrate metabolism.


Advances in paediatric practice

Diagnosis and management of paediatric practice in Australia

Almost a whole morning was devoted to paediatric research. Diagnosis and management of paediatric CFS/ME in Australia was discussed by Sarah Knight (Melbourne, Australia). An online survey was sent to registered paediatricians. She pointed out that there are more challenges in adolescence and most with this illness miss on average a year of school. 39% of the National Network of Paediatricians see patients with CFS/ME. A large number of comorbidities were diagnosed. There was wide variation is diagnostic and management practices, which may reflect a lack of knowledge of diagnostic criteria and a paucity of management guidelines.

Impaired range of motion

Peter Rowe (Baltimore, USA) presented work on the impaired range of motion (ROM) in adolescent CFS/ME. 55 patients and 48 matched “flexible” controls were studied. Impaired ROM was more common in CFS/ME than controls. There was wide overlap with Ehlers Danlos Syndrome (EDS) with a number of postural abnormalities such as slumping. There was abnormal range of movements in the limbs and spine, which were worse for 1-2 days after longitudinal strain therapy in a subset, but there was eventually overall improvement in CFS/ME symptoms after the therapy.

Tracking post-infectious fatigue

Tracking post-infectious fatigue in a clinic using routine lab testing was addressed by Gordon Broderick (Florida, USA). 301 adolescents following diagnosis on infectious mononucleosis were studied and followed over 24 months. Incidence of CFS/ME at 6, 12 and 24 months was 13%, 7% and 4% respectively. Standard lab tests were performed at each point. 13 patients (all female) had a diagnosis of CFS/ME at 24 months. At 6 months, ACTH was lower and glucose was higher in those that were still ill at 24 months. Estradiol was lower and T4 was higher at 12 months. At 24 months neutrophils were above normal and basophils decreased. These results help to support early assessment of those who may go on to develop CFS/ME over time.

Delayed hypersensitivty reactions to foods

A further presentation by Peter Rowe (Baltimore, USA) concerned the prevalence of delayed milk-protein hypersensitivity in young adults with CFS/ME. Children who were “picky” eaters were associated with non-IgE mediated food allergies. Characteristic symptoms were epigastric pain and other gastro-intestinal symptoms. There was no mast cell activiation. There was a higher than expected prevalence in those with CFS/ME. Strict dietary avoidance led to clinical and histological response. The diet needs to be rigid, and supplements with multivitamins and calcium is needed.

Impact of CFS/ME on adolescence

Peter Rowe then looked at the impact of CFS/ME in adolescence. Self-reported quality of life is significantly lower for adolescents and young adults with CFS/ME compared to healthy controls, and lower than scores reported for adolescents with other chronic health conditions, such as cystic fibrosis, epilepsy, diabetes and renal transplants, and comparable to scores for those with fibromyalgia and paraplegic cerebral palsy.

What Australians adolescents find helpful in managing CFS/ME

Katherine Rowe (Melbourne, Australia) had looked at what young people find helpful in managing their chronic illness. She had studied 788 people over 18 years. 1200 questionnaires were returned. An individualized plan of their own allowed them control over their lives again and was very important. Included in this should be a pleasurable out-of-home activity each week. Not being believed was the most difficult thing to handle. “Quacks” saying they could cure the illness was very upsetting and a lot of money was wasted by parents in this way. Loss of social contacts often led to depression, but this is a healthy response. SSRIs were used. Engagement in education was the best predictor of functional outcome.

Her further paper looked at whether functional outcomes were associated with depression at presentation. Average duration of illness prior to first visit was 15 months. 25% were significantly depressed compared to base rate of depression in adolescents of 20%. Not being believed, difficulty remaining engaged with school and severity of symptoms were contributing and perpetuating factors. Functional ratings at follow up were less good than the non-depressed group, but the overall duration of the illness was not significantly different.

Sleep education in Japan

Japanese are one of the most sleep-deprived groups of people, and Seiki Tajima (Hyogo, Japan) talked about sleep education carried out since 2007, to help prevent school non-attendence in junior high school and to help prevent risk of paediatric CFS/ME. Teachers and lifestyle educators were involved. 83% of patients (66) with school non-attendence fitted the criteria for CFS/ME. Incidence of school non-attendence decreased year by year, with all of the group attending regularly by 2012.


Advances in brain research

PET scanning

Neuroscience of fatigue and CFS/ME using PET was presented by Yasuyoshi Watanabe (Osaka, Japan). PET molecular and functional imaging is used to demonstrate brain dysfunction. Results of large studies in Japan showed reduced binding potential of 5HTT in CFS/ME patients, and this correlated with the pain scores. PET scanning could also be used for differential diagnosis. There were correlations between gastrointestinal symptoms and binding potential of 5HTT, and PET studies on neuroinflammation corresponded to activated microglia. fMRIs showed changes or reversible atrophy in the prefrontal cortex and a mirror system of fatigue (MEG). There were also changes in circulation from acute to chronic phases. Watanabe stressed now the need to look more at what is happening in healthy people.

EEG peak alpha frequency

Marcie and Mark Zinn (California, USA) then discussed their work on EEG peak alpha frequency associated with CFS/ME, as disabling fatigue and cognitive impairment are cardinal symptoms. The first presentation was to evaluate the relationship between EEG peak alpha frequency in CFS/ME compared to matched controls. Findings were consistent with reduced efficiency of thalamo-cortical connections in CFS/ME patients. And this correlated with reduced ability to coordinate cognitive symptoms. There may be prognostic value to facilitate the evaluation of CFS/ME as part of the diagnostic regimen. The second presentation looked at cortical hypoactivation during resting EEG in those with CFS/ME, and suggested central nervous system pathology. Exact low resolution electromagnetic tomography (ELORETA) could be applied to the understanding of brain fog. There were elevated delta sources in CFS/ME, with the highest percentage of voxel activations mainly in the left hemisphere regions of interest. Implications of abnormal delta sources can include speech difficulties, as Broca’s area is involved, and a possible indication of limbic encephalitis. No patients with psychiatric comorbidity were included in these studies.

Meta-analysis of cognitive functioning

Susan Cockshell (Adelaide, Australia) had investigated cognitive functioning in CFS/ME, using meta-analysis of previous studies and using that information to study a group of those with CFS/ME. Out of 4000 abstracts, 50 reported cognitive symptoms. She then studied 50 patients and matched controls. The main cognitive deficit found in those with CFS/ME appears to be a slowing in information processing speed. All were motivated to perform well. After testing it took 2-3 days for the CFS/ME patients to recover from the resultant fatigue.


Revision of the IACFS/ME physician's primer

This panel session highlighted the changes that have been made to the new edition of this manual for physicians. Most of the authoring committee were present and Ken Friedman (Vermont, USA) summarized the changes. Particular important changes included a section on the Severely Ill, and a comprehensive index.

There was much discussion from the floor including a plea from Dr Lily Chu (California, USA) to include more issues relating to mortality in the next revision.

The conference was summarized by Dr Anthony Komaroff and that summary is available on line.


Immunology workshop

Eight professional workshops were then held throughout the first day. I attended the immunology workshop outlined below:

Dr Dan Peterson chaired this and introduced the session with a brief discussion about our body defences, such as the skin, mucus membranes, stomach enzymes, bacterial toxins in GI tract, phagocytes and natural killer (NK) cells. He explained the innate and adaptive immune systems which interact via the cytokines. A number of presentations by immunology experts then followed.

1. Sonya Marshall-Gradisnik (Gold Coast, Australia) who gave an overview of her work and the establishment of the $150million building attached to Griffith University—the National Centre for Neuro-immunology and Emerging Diseases. She discussed the role of NK-cells, residing in the immune system. They influence the adaptive immune response and kill abnormal cells. An envelope in the cell contains granzymes, which pass through a protein via perforin pores. The abnormal cell is lysed through a cell-death pathway. LAMP (membrane proteins) encapsulate granzymes and perforin. NK-cells bind to target cells. Chemokine receptors (KIRs) sneak out infected cells. There are 2 types of KIRs (killer immunoglobulin-like receptors): inhibitory and activating. MicroRNAs control the function of the NK-cells. There are two NK phenotypes—“ dim” and “bright”.

The current status of CFS/ME is that there is no diagnostic test, pathology is unknown but there is consistency of NK-cell lysis. A snapshot analysis of moderately ill CFS/ME patients was done looking at lytic proteins, to see if lysis and phenotypes are consistent over time. NK-cells are found to be down in function over time, and there is a significant reduction in “bright” over time. The question was asked “Do lytic proteins play a role in CFS/ME?” Granzyme B decreases over time. Impaired degranulation is suggested. There was significant reduction in lysis in the severely ill groups. There were significant differences between severely ill and controls in NK phenotypes (CD158b+ and CD158a/h+) with reduced activation. A number of microRNAs were significantly reduced on NK cells, which influence efficiency.

2. Sharni Hardcastle (Gold Coast, Australia) looked at their severe cohort. And the adaptive immune system. There were alterations in T-regulatory cells and increased B-cell activation. There were some cytotoxic cross-over cells. In the severely ill patients there was an increase in plasma dendritic cells, increased naïve and plasma B-cells, decrease in transitory and regulating B-cells and a decrease in ɣɗ1 phenotypes. Regulatory NKT-cells were increased in the severe patients. CD8a and CD4 were changed in the severely ill.

3. Nancy Klimas talked about cytotoxic T-cells and the immune system in CFS/ME. This is part of the acquired system. NK-cells evolve first and the acquired immune system develops over time. 5% of the immune system is in the blood, the rest is everywhere else, particularly in the gut. The cells need to be close together (e.g., in lymph nodes) to be efficient. There are more glial cells (white blood cells) than neurons in the brain. There is duality of the immune system: a) humoral (NK-cells) and b) cell-mediated (T-cells). T cells only recognize antigen associated with MHC (major histocompatibility complex ) molecules on the cell. This is very specific. Perforin and granzymes poke holes in the cells leading to death. Networks of communication may get severed. Ways to reconnect need to be modelled. Perforin has been found to be down in T-cells.

Biomarkers can be treatment targets. E.g., Neuropeptide-Y connects the immune system and the nervous system. IN CFS/ME there is high NPY and low CD-26.

4. Paula Waziry (Miami, USA) discussed gene regulation. There are variable symptoms in CFS/ME. Viral reactivation may occur due to genetic, environmental and epigenetic effects on gene expression. PBMCs are involved (B and T). Mononuclear cells have a nucleus! And everything is regulated at many levels by gene expression. Data shows decreased levels of human microRNAs in CFS/ME. In EBV there may be impaired NPC function, but interferon will “undo” the reaction.

5. Konstance Knox (Wisconsin, USA) had looked at B-cell function and the pathogenesis of CFS/ME. B-cells are produced in the marrow and travel to lymphoid organs. They are part of the adaptive immune system. 2-5% of serum IgM/IgG is not directed at specific pathogens. They are naturally occurring antibodies. Work has been done on mice (Jay Levy).

Regulatory B-cells (0.5% of B-cells): a) secrete IL-10 (anti-inflammatory) which restores TH-1/TH-2 balance and b) secrete TGF-β1 which induces apoptosis. B-cells receive and present the antigen. She mentioned the rituxin studies. The drug is directed at CD20. She questioned whether there may be an increased risk of lymphoma in CFS/ME. The B-cell may be a very important component of CFS/ME.

6. David Baewer (Wisconsin, USA) Talked about the role of serology in the diagnosis of the herpes virus, and how to order diagnostic studies. There are limitations in serology in CFS/ME, but there is a body of literature and a need to rule out a herpes diagnosis in CFS/ME. There are billions of herpes viruses in our systems, and we will all have viral antibodies. Positive IgM equates to active infection leading to latency for life. Reactivation to IgM response is rare. Therefore IgM will be of little use. Immune dysregulation means tests are unreliable. Molecular testing for herpes is more reliable. Qualitative tests for virus DNA is 85% positive in the population. Virus replication needs to be tested using reverse transcriptase PCR. Late transcript viral RNA is more reliable. The virus actively transcribes active gene products. There may be a smouldering herpes infection going on.

7. Troy Querec (Atlanta, USA) discussed cytotoxicity in a multicenter trial looking at impaired NK-cells. e.g. CD107a functional assay. He stressed the point that shipping time decreases cell viability, and discussed methods of shipping. Impaired NK function is a promising biomarker. Functional assays are not always available. A pilot study is planned to assess design variables.

8. Isabel Barao-Sylvestre (Nevada, USA) had looked at NK-cells and cytokines. Cytokines are LMW proteins. There is no single organ source. Lymphokines come from lymphocytes, chemokines are functional, interleukins are messengers between leucocytes. There are chains of cytokine action. They are potentially useful markers. She talked about therapeutic antibodies being used in autoimmune diseases, and IgG subclasses, with deficiencies in some patients in CFS/ME.

9. Mary Ann Fletcher (Miami, USA) – was described as having much wisdom after 35 years of research into this illness. In 1990 she found reduced NK function with elevated pro-inflammatory cytokines. These findings have been confirmed around the world and are potential biomarkers. Age of sample, technique used, and identified diagnosis of the patient are all important factors. Their team is ready to go ahead.

10. Dennis Mangan (California, USA) is a communications expert, which seems apt in the field of immunology . He describes communication as having a sender and receiver with a message flowing between them. Modification and sensitization is possible.

11. Beth Unger (Atlanta, USA) describing herself as a “non-immunologist” summed up the workshop. She described it as a very complex situation. There needs to be very good laboratories. With a focus on methods, there are excellent prospects. A lab has the potential to do almost “anything” if it is deemed important enough. The immune system seems crucial to understanding this illness.

Poster presentations

89 posters were displayed and will be summarized later.

Oral Complications in Sjögren's Syndrome and Chronic Dry Mouth

By R. Sanderson

Dry mouth and various oral and dental complications are problematic for many people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), or Fibromyalgia (FM). Persistent dryness of the mouth could indicate an autoimmune illness like Sjögren's, linked to poorly functioning or damaged salivary glands, or be the result of side effects associated with many medications. Either way, it is a problem that warrants prompt medical or dental attention.

Dental caries, which refers to localized disease that causes decay and cavities in teeth, and oral problems have a tendency to progress much more rapidly when there is poor salivation and ongoing dryness. The goal of this article is to provide information about the serious and often devastating consequences of persistent dry mouth and treatments that can help to protect teeth and restore oral health.

Ed. Note: This article features information about oral complications, research highlights, and guidelines for people living with Sjögren's Syndrome and chronic dry mouth. Most of the information used in this article is based on a lecture given by Dr. Athena Papas for the Greater Boston Sjögren's Syndrome Support Group held on December 5, 2013 at Tufts Medical Center, Sackler Building, in Boston, MA. Additional data is included in order to provide some background information and more resources for our readers.

This material was researched and prepared by a layperson with ME/CFS and Sjögren's. Every effort has been made to accurately convey the information delivered by Dr. Papas and represent the research of other scientists brought up in this material. As always, consult with your health care provider for advice and further evaluation of new or worsening symptoms. Please see our Disclaimer

The first part of the article discusses issues around diagnosing Sjogren's Syndrome. If you suffer from dry mouth and are more interested in issues/treatments for this general condition, you may want to skip to the part of the article beginning with "How to minimize oral complications and maximize oral health and comfort."


Challenges of current diagnostic criteria and future screening methods

Athena Papas, DMD, PhD, is the Erling Johansen Professor of Research, the Co-Head of Geriatric Dentistry, and the Director of the Oral Medicine Department at Tufts University School of Dental Medicine. Dr. Papas has published numerous research papers based on her extensive clinical experience in Geriatric Dentistry, Sjögren's Syndrome, medically compromised patients, and xerostomia. At the December 2013 meeting, Dr. Papas discussed research updates and oral concerns and challenges of Sjögren's in her presentation titled, "Living with the Oral Complications of Sjögren's Syndrome."

Dr. Papas began her presentation with a short, educational video, "Does your patient have Sjögren's Syndrome?" released for dentists. The following is a brief description of Sjögren's taken from this video:

"Although hallmark symptoms are dry eyes and dry mouth, Sjögren's may also cause dysfunction of other organs such as kidneys, gastrointestinal system, blood vessels, lungs, liver, pancreas, and the central nervous system. Patients may also experience extreme fatigue and joint pain and about ten percent of patients develop lymphoma of their salivary glands. All instances of Sjögren's are systemic, affecting the entire body."

Sjögren's can exist alone, as a primary condition, or with another connective or autoimmune tissue disease such as rheumatoid arthritis, systemic lupus erythematosus, scleroderma, and other conditions.


Early diagnosis of Sjögren's remains a challenge

Sjögren's is one of the most commonly under-diagnosed autoimmune diseases, often taking 5 to 8 years before a diagnosis is made.

While there are several techniques to assess salivary gland and ocular involvement, tests for certain autoantibodies in serum, and methods to demonstrate tissue changes, no single test is specific and sensitive enough to make a diagnosis.

Lack of international consensus regarding what defined positive evidence of the illness and ways to differentiate the two variants of the illness were some of the reasons for revision of the classification criteria for Sjögren's.

In April 2012, the latest version of the classification criteria was released by a group of international experts which included new details, rules and thresholds for tests and how these need to performed and interpreted. (Source: The Kelley's Textbook of Rheumatology, 9th edition).

The new criteria was intended, in part, to help ensure uniformity in participants selected for research.

To meet the classification criteria, there must be objective evidence in 2 out of 3 tests. For example, one of these tests must show one or more sites of inflammation per 4 mm squared area of glandular tissue for a positive result, according to the National Institutes of Health's release of April 2012, "New classification criteria released for research on Sjögren's Syndrome."

Clinicians and researchers who treat Sjögren's patients find these criteria can only detect patients with an established disease, that is, when their glands have already become damaged.

Patients will typically need to consult with at least two clinical specialties for evaluation and testing before a diagnosis can be made. The high cost of diagnostic tests, risks and discomfort associated with some of the procedures, and amount of time required to complete the testing/diagnostic process causes significant delay in diagnosis.

Continued disagreement and proposed changes to the 2012 classification criteria has gotten in the way of research for new treatments. All of the aforementioned issues underscore the importance of finding new ways to diagnose Sjögren's at an early stage of the illness.


Turning to saliva as a diagnostic tool

Saliva is often described by researchers and doctors as a mirror of the body and its well-being. It contains valuable diagnostic biomarkers which can help to screen for periodontal and other oral diseases, various cancers, systemic illnesses, and other conditions.

Other benefits of saliva-based tests are that they are less invasive and are rapid and cost-effective ways to screen for illness or detect early signs of illness.

Saliva analysis has been used, in some capacity, over the past 20 years to evaluate various medical problems; however, the field of research specifically devoted to disease detection and surveillance is called salivary diagnostics.

An investment made by the National Institute of Dental and Craniofacial Research (NIDCR) in saliva analysis over ten years ago, has generated significant advancement in salivary diagnostics. The NIDCR research initiative funded salivary diagnostic technology development at several research centers across the United States.

This research has led to discovery and development of a "diagnostic toolbox"— identification of components in human saliva, with biomarker profiles which can be used in the diagnosis of disease. (Source: A Primer on Salivary Diagnostics, published by the American Dental Association).


The future of salivary diagnostics

One of pioneers in salivary diagnostics is David T.W. Wong, D.M.D., D.M.Sc., the Associate Dean of Research at the University of California-Los Angeles (UCLA). Dr. Wong is also the Director at the UCLA Center for Oral/Head & Neck Oncology Research and Director of the Dental Research Institute at UCLA. Dr. Wong and the UCLA Dental Research Institute group have been instrumental in the development of salivary diagnostic biomarker profiles, which include: proteome, transcriptome, microRNA, metabolome and microbe. The Wong Lab/UCLA has established a research base that can serve as the scientific foundation for future dental and biomedical studies.

The UCLA research group has also developed statistical and informatics tools for salivary biomarker detection and validation. A prototype of this technology is a portable, integrated system that can rapidly detect multiple salivary proteins and other substances. This is an example of "point-of-care" technology that can be used at a healthcare provider's office to analyze oral fluid samples for disease or early signs of disease, eventually leading to chairside screening. Before this becomes common practice, scientists need to further investigate the potential diagnostic value of saliva and develop reliable and feasible technologies with high detection sensitivity. The future use and integration of salivary diagnostic technology may strengthen interdisciplinary patient care by changing the role that dentists and dental practitioners will play in healthcare. (Sources: A Primer on Salivary Diagnostics, American Dental Association. Salivary Diagnostics, The Wong Lab/UCLA School of Dentistry, The Dental Research Institute website).


Potential salivary biomarkers for Sjögren's

Research at the Department of General Dentistry at Tufts University School of Dental Medicine, Boston, MA has focused on both biomarkers and treatment of Sjögren's.

Dr. Athena Papas and Dr. Mabi Singh, who both treat high risk patients at the Tufts Dry Mouth Clinic, were two of several researchers from the Tufts University School of Dental Medicine to partake in a multi-center research study on salivary biomarkers. The aim of this study was to determine if biomarkers that could be used for diagnosis of Sjögren's are present in saliva.

"Discovery of putative salivary biomarkers for Sjögren's Syndrome using high resolution mass spectrometry and bioinformatics," published in the Journal of Oral Science, January 2012, found a biomarker that is unique to Sjögren's. They describe this biomarker as a "proteolytic peptide originating from human basic salivary proline-rich protein 3 precursor."

The research group concluded that the salivary biomarkers which they discovered, using the methods of detection and analysis detailed in the study, have the potential of serving as diagnostic/prognostic tools for Sjögren's Syndrome. A link to the full text of this research paper is provided at the end of this article.


How to minimize oral complications and maximize oral health and comfort

Dr. Papas has served as the principal investigator of numerous clinical trials and co-investigator of many research studies. She also possesses clinical expertise in the oral healthcare of geriatric patients, patients who are medically compromised as well as those with Sjögren's Syndrome and chronic dry mouth. Her combined and extensive research and clinical knowledge is evident in Dr. Papas' appreciation for the difficulties and complications that patients experience with Sjögren's/chronic dry mouth.


Common causes of tooth decay, dental problems, and oral pain

Saliva is essential for oral health. Once patients lose their saliva, they are at risk of losing their teeth. The effect of persistent dryness in the mouth may not always be understood by healthcare providers. Some, simply lacking knowledge in how to properly care for dry mouth, have given patients very poor advice. It is so important, but often very difficult, for patients to receive expert assistance at the early stages of their dental and oral complications. Many arrive at the Tufts Dry Mouth Clinic with teeth so eroded or broken that only jagged pieces protrude from the gums—the alarming discovery is many of these patients had extensive dental work, but it was no longer working. Dr. Papas tried to explained how this could happen.

Saliva is what keeps the enamel of teeth hard. Low amount of saliva production or loss of saliva leaves tooth enamel much more vulnerable to a wide range of dental problems. It is the weakening and erosion of tooth enamel which leads to many devastating complications.

The following list is a summary of the recognized as well as lesser known causes of tooth decay, deterioration, and erosion:

Acid in foods and beverages can affect teeth by accelerating demineralization of teeth (i.e., removing vital minerals). Frequency of consumption also matters—it is better to drink an acidic beverage all at once, rather than to keep sipping on it.

Acid reflux, found in at least half of Sjögren's patients, can cause stomach acids to backflow into the mouth, eat away at enamel, and even get at the pulp. Indications of acid backflow are soreness at the back of the throat, shiny amalgams, or signs of the enamel becoming eaten away around the amalgam. This acid can sometimes be so severe that it has completely worn away a person's teeth.

Brushing too hard can wear the teeth down (referred to as toothbrush abrasion) and brushing immediately after consuming acidic foods or drinks can make matters worse, by stripping away enamel.

Dryness cause teeth to dry out; when teeth dry out, they are much more likely to crack. Dryness can be the result of an underlying disease, like Sjögren's, or as a side effect from many drugs. Every effort needs to be made towards restoring moisture to the mouth.

Failed dental work, even in patients who have undergone a lot of dental work, is greatly due to inadequate preventative care. Work done on teeth that are already weakened or in an unhealthy condition or in a mouth with chronic dryness will simply not hold!

Fillings falling out of teeth often happens in teeth that are not hard enough. In most cases, it is not the filling but the teeth which have changed or deteriorated. This problem points back to causes of failed dental work. Getting a root canal or getting a tooth crowned does not eliminate future problems nor the need to continue protective therapy. In fact, teeth that have been worked on require even more attention and ongoing fluoride treatments or preventative measures. A tiny gap can easily develop along the edge of a crown and allow debris or bacteria to seep in.

Inflammation can occur in salivary glands as well as in the gingival margins of the teeth. In Sjögren's, it usually does not go below the gum line, like in periodontal disease.

Thick saliva; the watery part of saliva is the first to go in Sjögren's. Advanced dryness caused by the lack of saliva or damaged glands in Sjögren's can be so profound that a wooden tongue depressor will remain stuck on a patient's tongue.

Tooth Decay, particularly in Sjögren's, often occurs at the gum line, especially as gums start to recede. The root is much more sensitive to decay than the crown of the tooth. When there is a lot of tooth decay along the gum line, the tooth can shear right off.

Triggers of oral pain, sensitivity, and burning sensations

- Candidiasis: As saliva decreases, the development of candidiasis increases. A significant percentage (60%) of Sjögren's patients have candidiasis, especially the erythematous variant. This will present as red, irritated oral tissues and a red, raw tongue. It causes a lot of soreness and sensitivity inside the mouth. It can also develop as cracks at the corners of the mouth.

- Burning tongue/burning mouth: The lack of lubrication in the mouth can make the tongue become dry and rough due to friction against teeth and causes burning sensations. An interesting finding is that women have more taste buds than men. This difference may point to early means of survival that women were born with as they were the ones to determine if plants or foods were safe to eat by tasting them for their bitterness. When nerve endings on all of these extra taste buds become dry, irritated or inflamed, the patient will experience a burning mouth.


Treatments that make a difference and reduce tooth decay

Dr. Papas reviewed many treatment options which can help to minimize oral complications and maximize overall comfort and well-being. While there are many over-the-counter products advertised for dry mouth, she cautioned these products are primarily for comfort. They can be used, but they will not treat or protect the mouth or teeth. Treatments that make a difference, many times a prescription product, will help to stimulate salivation, restore moisture, protect and restore tooth enamel, and prevent anticipated complications.

The most important treatments and techniques for patients to start with are listed below:

Fluoride toothpaste – prescription-strength: Daily use of prescription-strength fluoride toothpaste is recommended (brand name, Colgate PreviDent). Research has shown that Sjögren's /dry mouth patients had less tooth decay with regular use of fluoride (i.e., as toothpaste, oral rinses, treatments provided by the dentist).

Fluoride varnishes: New ways to deliver fluoride, as a clear film that gets brushed on by the dentist. Discuss this option with your dentist.

Brushing techniques: Be sure to brush your teeth correctly. Don't scrub. Power toothbrushes with sonic technology are recommended for Sjögren's /dry mouth patients. These are found to more thoroughly remove plaque from teeth and gums.

Night-time routine: This should include brushing teeth with a prescription-strength toothpaste, followed by an application of MI Paste™ over the teeth, and then going to sleep (without rinsing). This regimen serves as an overnight treatment that will help remineralize and protect teeth.

Remineralize teeth by using a topical cream like MI Paste™ that contains calcium and phosphate. Place a small dab on a fingertip and spread it over teeth. Note: MI Paste contains RECALDENT™, a special milk-derived protein which helps to release the active ingredients. It may not be suitable for people with milk protein allergies. It is usually provided or sold by a dentist or an oral specialist, although it is sold at several online stores. Discuss this treatment option with your dentist.

Increase salivation with use of sialogogues: Sialogogues are agents or drugs that help to increase/stimulate salivation. Two of the most commonly used systemic sialogogues are pilocarpine (brand name, Salagen) and cevimeline (brand name, Evoxac). These are prescription drugs and may cause side effects in some patients. Research has shown that patients who had used Salagen for 4 years had much less tooth decay.

Increase salivation by chewing: Chewing gum can also help to stimulate production of saliva. Xylitol gum is preferred because it helps to generate moisture in the mouth. Too much xylitol can cause diarrhea; therefore, the recommended consumption is no more 8 pieces per day.

Improve salivation by massaging glands: See massage techniques to relieve painful or swollen salivary glands, described in detail, at the end of this list.

Chlorhexidine: an antimicrobial oral rinse, available by prescription (brand name, Peridex, Periogard) is used to treat swollen or infected gums.

Anti-inflammatories, like Celebrex, have been shown to reduce inflammation in periodontal disease. A short course may help Sjögren's/dry mouth during a flare.

Omega 3 fatty acids can help to reduce inflammation and improve salivation.

Lubricate the inside of your mouth with extra virgin olive oil or vitamin E capsules.

Increase dental cleanings/exams plus fluoride treatments—ideally, four times per year to effectively manage and care for Sjögren's /chronic dry mouth.

Check for early signs of lymphoma, very important to do in Sjögren's as lymphoma is detected in about 10% of patients— don't ignore little things—a warning by Dr. Papas.

Dental implants, consider implants if all else fails. There have been 200 implants done at the Tufts Dental Specialty Clinic with a 97% success rate. Implants can also serve as a base for dentures.


Massage techniques to relieve painful or swollen salivary glands

The parotid glands are located in the upper part of each cheek, close to the ear, and secretions from the glands have to pass through a complex pattern of ductwork. The parotid glands are encapsulated and have a thick fibrous coating. These glands can become obstructed with a mucus plug or stones in the ducts and cause swelling, pain and damage to the ducts.

Therefore, it is very important to keep the flow of saliva moving and good way to encourage flow of saliva is by massaging the glands.

For parotid glands, place two fingers behind the ear and slide them forward along cheek, while applying gentle pressure.

For the submandibular/sublingual glands, place two fingers under the jaw and slide them forward, along the edge of the jaw line to promote flow of saliva into floor of the mouth.

These are self-applied massage techniques that can help to keep saliva flowing. Warm compresses can be used to soothe painful glands.


 A promising treatment for dry mouth is in the pipeline

Dr. Papas ended her presentation with encouraging news about her work with Dr. Howard Green, at Harvard Medical School, who had developed artificial skin for severely burned patients. They have conceived a treatment plan for a moisturizing agent that would be delivered by way of a mucoadhesive film (attached to the mucosa) into the oral cavity. They have asked the Forsyth Institute in Cambridge, MA to help them create this product, and it has shown an interest in it.


References

"A Primer on Salivary Diagnostics", American Dental Association, 2009. 

"New classification criteria released for research on Sjögren's Syndrome," National Institutes of Health's New & Events, Release of April 11, 2012: http://www.nih.gov/news/health/apr2012/nidcr-11.htm.

Shiboski SC et al, "American College of Rheumatology classification criteria for Sjögren's syndrome: A data-driven, expert consensus approach in the Sjögren's International Collaborative Clinical Alliance Cohort", Arthritis Care & Research 64, no. 4 (2012): 475–487, doi: 10.1002/acr.21591. Full text of this article (Wiley Online Library) as PDF: http://onlinelibrary.wiley.com/doi/10.1002/acr.21591/pdf.

Spielmann N and Wong DT, "Saliva: diagnostics and therapeutic perspectives," Oral Disease 17, no. 4 (2011): 345–354, doi:10.1111/j.1601-0825.2010.01773.x. Full text of article as NIH Public Access Author Manuscript: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3056919/

St. Clair, EW. "Sjögren's Syndrome," in The Kelley's Textbook of Rheumatology, 9th ed. Gary S. Firestein, M.D., et al (Philadelphia: Elsevier/Saunders, 2012), Ch. 73.

Zoukhri D  et al, "Discovery of putative salivary biomarkers for Sjögren's syndrome using high resolution mass spectrometry and bioinformatics," Journal of Oral Science 54, no. 1 (2012). Full text of this article: https://www.jstage.jst.go.jp/article/josnusd/54/1/54_1_61/_pdf.

 

For additional information on salivary diagnostics/salivaomics

Dr. David T. Wong extends an invitation to anyone who would like to explore more of research done by the UCLA School of Dentistry, Dental Research Institute to visit their website, Salivary Diagnostics

A chart that illustrates the scientific development of salivary diagnostic toolboxes can be seen at: Salivaomics Knowledge Base (The Wong Lab, at the UCLA School of Dentistry, Dental Research Institute).

Listen to an informative Podcast by the American Association for Clinical Chemistry, September 2012 issue, that features Dr. David T. Wong. In this 15 minute interview, Dr. Wong reviews one of his recent research papers and explains how the evaluation of RNA in saliva has the potential of becoming an emerging diagnostic technology in disease detection: "The Human Salivary RNA Transcriptome Revealed by Massively Parallel Sequencing." The link for this podcast can also be accessed on the Home page of The Wong Lab /UCLA Dental Research website.

Books about Pain and Pain Management

 

The Massachusetts CFIDS/ME & FM Association does not assume any responsibility for the outcome of treatments or other self-care strategies described in any of the listed books, that might be undertaken by readers and we recommend individuals always consult with their healthcare providers before trying any new treatment, supplement, or healthcare product.


 Pain Free 1-2-3: A Proven Program for Eliminating Chronic Pain Now, by Jacob Teitelbaum, MD, 2005, ISBN: 0071464573.   


Pain Free 1-2-3 is another informative and engaging book to come from Dr. Jacob Teitelbaum, author of the well-known guide for ME/CFS and Fibromyalgia (FM), From Fatigued to Fantastic (now in its 3rd edition). The target audience for this particular book consists of individuals with FM, myofascial pain or chronic pain. Though Dr. Teitelbaum touched on the importance of decreasing or eliminating pain when someone has ME/CFS and/or FM in all the editions of his first book, this book allows him to expand on this topic and it nicely complements the first series. 

Dr. Teitelbaum starts out by explaining what sorts of things can help to promote healing and repair tissues as well as what sort of things may put stress on one’s body and cause pain. The treatment strategy formulated by Dr. Teitelbaum (which he claims can eliminate chronic pain) includes recommendations such as: striving to get the best possible nutrition and quality sleep, correcting one’s hormonal deficiencies, learning how to identify and eliminate pain triggers (including getting treated for any persistent infections since they put a strain on the immune system), and learning about the many types of pain and how to deal with each of these. [N.B. There is no solution to the pain from lactic acid build-up due to mitochondrial dysfunction except time and bed rest. Your body has to break down the lactic acid to dispel the pain.—Ed.]

The second half of the book summarizes numerous treatment options, including herbal /natural remedies and alternative therapies, prescription therapies, and/or a combination of both approaches. He also states the best order in which to try these and how they will be most beneficial. (It is understood that treatments should be pursued while under the care of one’s doctor.)       

Though this book offers a lot of practical information, the way it is marketed (i.e., the flashy titles, making things sound so easy to do, or making rather incredible claims) is a negative and may actually discourage interest in this book. It is not clear why Dr. Teitelbaum has chosen this type of delivery style considering his extensive knowledge about ME/CFS and FM and chronic pain as the medical director of the Center for Effective CFS/Fibromyalgia Therapies in Maryland. On the positive side, if readers can get past the packaging, they will appreciate the value of the information in this book and will sense the author’s optimism and desire to enlighten readers.


Trigger Point Therapy for Low Back Pain: A Self-treatment Workbook (New Harbinger Self-Help Workbook), by Sharon Sauer, CMTPT, LMT and Mary Biancalana, MS, CMTPT, LMT, 2009, ISBN: 1572245638.   


As the title implies, this book is intended for individuals who suffer from low back pain and who would like to learn more about what is causing their pain and find out what they could do to alleviate some of the pain. The type of pain discussed in this book is muscle pain, more specifically, pain coming from the tightening of the myofascia—the thin, fibrous tissue that encloses layers of muscles and supports the musculature of the body. Changes within this tissue present as “trigger points” which are painful knots that develop in the muscle fiber and cause constriction of nerves and blood vessels and this in turn, causes pain and referred pain.

Myofascial trigger point therapy is a type of bodywork done by medical practitioners and/or trained therapists using manual and physical techniques to find (through palpation) and reduce these knots and myofascial constriction, but considerable relief can be also achieved at home though various self-applied methods. Therefore, this book contains what two knowledgeable therapists in this field and members of the International Myopain Society, Sharon Sauer and Mary Biancalana, want to share with readers.

The authors write from personal and professional experience and are very careful and sensible in how they communicate with readers. Their first recommendation is that anyone with low back pain be thoroughly evaluated by a primary care physician and/or specialist for all possible causes. Patients are also urged to get their doctors’ approval before participating in any of the home exercises and/or seeking therapy from licensed practitioners using this discipline.

This is a very user-friendly book, which is not overly long (as it concentrates only on muscle groups involved in lower back muscle pain), and in which the information is conveniently broken down into 17 small chapters. Once the basics are covered, a chapter is devoted to each of the ten specific muscle groups associated with low back and/or buttock pain, as well as trigger points that are activated and causing pain.

Symptoms and patterns of muscle pain/referred pain for each group are well explained and in many cases, accompanied by illustrations and diagrams. One chapter, in particular, seems very helpful because it provides a reference chart listing general problems and the muscle groups associated with these, including a notation as to which chapter discusses this particular muscle group.

Treatment recommendations, within each chapter for each muscle group, consist mainly of helpful stretches, ways to apply pressure against painful areas and promote release of knots, range of motion exercises with easy to follow diagrams, and instructions for how to use self-care tools and other therapies (i.e., backnobber, therapy balls, pillows, use of heat, etc.).

This book is effective in enlightening readers about myofascial pain and trigger point therapy. As mentioned before, content is limited to the lower back muscle groups.  It is important to note this book solely concentrates on trigger point therapy and this type of pain and it does not include any information on fibromyalgia in particular. We do not think this is a problem because the at-home techniques and tips could be beneficial and this type of intervention has been included in recent fibromyalgia publications.


 Sciatica Solutions: Diagnosis, Treatment, and Cure of Spinal and Piriformis Problems, by Loren Fishman, MD and Carol Ardman, 2006, ISBN: 0393330419.

Dr. Loren Fishman, a specialist in rehabilitation medicine, researcher and professor at Columbia College of Physicians and Surgeons, and his wife, Carol Ardman, a freelance writer and editor, wrote this book because of the misunderstanding that surrounds sciatica and associated problems. This is a genuine problem noticed by Dr. Fishman himself, who has over thirty years of clinical experience. Therefore, they wanted to provide a book which clarifies this type of pain, explains how to better recognize it, reviews the kind of tests or care one might consider getting for it, and explains the wide range of treatment options, both conventional and alternative.

This is not a book about general back pain, which is often muscular in nature, but one that focuses on sciatica—a pain, neurological in origin, that typically runs along the sciatic nerve and causes distinct set of symptoms and pain patterns in the buttocks and the legs (i.e., numbness, “electric shocks”, and other peculiar sensations).

The book is divided into two parts. In the first part, Dr. Fishman goes over the multiple causes of sciatic-type pain and describes how it feels, but also differentiates it from other conditions which are often mistaken for it.

One chapter reviews basic components and functions of the nervous system (i.e., the interaction of the brain, spinal cord, the nerve fibers and nerve roots). Of particular interest are the illustrations of the spine, nerve root patterns and diagnostic diagrams.

Another chapter is dedicated to the diagnostic and nerve function tests used to diagnose sciatica-related problems or to evaluate nerve damage.

The last chapter in the first part offers an extensive review of the conditions associated with sciatica. Here too, the in-depth explanation of the Piriformis Syndrome—a condition affecting the buttocks when the sciatic nerve becomes entrapped and compressed, was found to be especially informative and unique to this book.

The second part of the book deals with treatment options and many things that patients can do on their own. It is understood that patients will have first sought appropriate medical care and evaluation from their primary care providers or specialists.

Recommendations include such things as strengthening abdominal, torso and core muscles, becoming educated about different exercise/movement techniques, and paying attention to daily routines, posture, and even one’s clothing, handbags and footwear.

Medical treatments, such as physical therapy, medical devices, and various mechanical techniques are reviewed.

An overview is provided on frequently used medications, injections and other invasive treatments, as well as various surgical procedures (including brief descriptions and reasons for these surgeries).

The book concludes with many types of nonmedical alternative techniques and the importance of nutrition and lifestyle changes. Dr. Fishman is a strong proponent of alternative treatments, like yoga, and promoting patient education.

This book is easy to read and comprehend, even though it contains some technical information. The authors have done a good job in how they have explained or illustrated this information. Their writing style is friendly and speaks to the readers.

This book would be especially beneficial for individuals who are just starting out with sciatica, because it provides them with the knowledge they need to make informed decisions. Individuals who might already be receiving medical care for this problem will find parts of this book helpful because it provides a better understanding about the mechanisms driving the pain and offers additional ways to manage it.