Interesting Findings Reported in Recent DM Research Studies on Sleep Disturbances

Dr. Katharine Hagerman, Research Associate at Stanford University Neuromuscular Division and Clinics, provides a summary of a recent DM2 sleep survey that has drawn criticism from international DM experts in Italy.

Restless Legs Syndrome and Daytime Sleepiness are Prominent in Myotonic Dystrophy Type 2
EM Lam et al; 2013, Neurology 81(2):157-64

A recent study headed by Dr. Margherita Milone from the Mayo Clinic in Minnesota outlining sleep disturbances in those with myotonic dystrophy type 2 (DM2) has drawn criticism from a group of international experts in Italy headed by Dr. Gabriella Silvestri.

Dr. Milone’s study examined the frequency of sleep disturbances by analyzing surveys filled out by 30 people with DM2, and 43 unaffected individuals. Her study found that those with DM2 had more clinically significant reports of daytime sleepiness, fatigue, altered sleep quality, and restless leg syndrome. Surprisingly, the study also found that obstructive sleep apnea was not a frequent sleep disturbance in DM2, going against previous small studies by Dr. Silvestri and others that estimated the prevalence of obstructive sleep apnea to be between 60% and 67% in DM2. 

Though Dr. Milone’s study was able to assess a larger number of affected individuals than other studies, Dr. Silvestri pointed out that it relied on paper-based surveys instead of more reliable clinical measurements from sleep monitoring.  Overall, studies on sleep disturbance in DM2 highlight the need for overnight and daytime sleep studies when individuals have symptoms that may stem from sleep issues, preferably performed in a sleep clinic that is able to differentiate between obstructive and central sleep apnea, along with assessing for sleepiness, fatigue, other forms of hypoventilation, periodic limb movements of sleep, restless leg syndrome, and REM sleep abnormalities.  

For the article abstract click here. 

Interesting Findings Reported in Recent DM Research Studies on Facial Recognition

A recently published study from Sweden reported impaired facial recognition in people with DM1, and indicated that there are brain differences that affect how faces are perceived and stored by people with DM1. Dr. Katharine Hagerman, Research Associate at Stanford University Neuromuscular Division and Clinics, provides a summary of the Swedish facial recognition study.

Facial Memory Deficits in Myotonic Dystrophy Type 1
J Lundin Kleberg, C Lindberg, and S Winblad (2014) Acta Neruol Scand

Three Swedish researchers recently assessed cognitive differences seen in people with type 1 myotonic dystrophy (DM1). Their previous studies had shown that people with DM1 had a reduced ability to recognize facial emotions, and this correlated with lower sociability. In order to further assess factors affecting sociability in DM1, participants were given pictures of 15 different faces, and were later asked to pick out which faces they had seen before from a set of 30 pictures. Overall, 36% of participants with DM1 had impaired memory of faces, compared to 13% of participants without DM1.

Those with DM1 who had impaired memory of faces tended to falsely recognize faces (false positives), and upon further cognitive testing this group had reduced performance in tests of spatial coordination and motor skills. The researchers believe the impaired facial recognition seen in some people with DM1 indicates deficits in how the information about faces is perceived and stored. They suggest future studies should use eye-tracking to see how people with DM scan pictures to store information. They also recommended conducting MRI studies to see how the brain may differ both in structure and function in those with DM.

For the article abstract click here.  

Dr. Danielle Sheypuk, a licensed psychologist in New York, NY, was the presenter for our most recent webinar—the last for 2013— titled “Coping with Depression Associated with Having a Chronic Health Condition.” Dr. Sheypuk not only share information about the different types of depression but also discussed when those concerns should be escalated.

A variety of options were suggested for coping with depression, including:

• Working with a therapist
• Meditation
• Staying active, both physically and mentally
• Medication
• Socializing
• Practicing a process of exploration, acceptance and integration

Dr. Sheypuk noted that the process of exploration, acceptance and integration may involve skills-oriented training, such as dialectical behavioral therapy (DBT). One of the goals of DBT is the acceptance of one’s situation, finding renewed meaning in life, and integrating chronic illness into daily living.

Additionally, Dr. Sheypuk, who is an expert in the area of dating and relationships, suggested maintaining intimacy in one’s life through dating and romance.

As the inaugural presentation in our Living with DM Webinar series, we discuss the decline of executive function in the CNS due to myotonic dystrophy, as well as strategies for managing this symptom, and an update on current CNS research.

Maurice Swanson, Ph.D., Professor of Molecular Genetics and Microbiology at University of Florida, Gainesville, and a team of researchers have found that the muscleblind-like 2 (MBNL2) protein in the central nervous system (CNS) may be responsible for the neurological impacts of myotonic dystrophy (DM), providing hope for new treatments. Muscleblind is a type of protein that plays an important role in switching proteins typically found only in babies to proteins found in adults. If this switch isn’t made, an imbalance exists that leads to myotonic dystrophy.

Dr. Swanson states that the team’s work seeks to understand what causes myotonic dystrophy beyond the mutations in the DM1 and DM2 genes.

Dr. Swanson examined which genes were affected by loss of MBNL2 in the brain and found more than 800 affected genes. Many of them had one thing in common: the encoded protein could be made in both fetal and adult forms and MBNL2 appeared to regulate which version was created, according to an article in Neurology Today. One persistent concern that people living with DM1 and DM2 have is the effects of this disease on the brain. “People who don’t have DM usually feel refreshed after a night’s sleep. Myotonic dystrophy patients do not routinely achieve a normal sleep pattern; instead, they have an interrupted series of sleep-wake patterns that do not allow for deep, restful sleep cycles”.

Dr. Swanson created a mouse that lacks the MBNL2 protein as an animal model for DM effects on the CNS. These mice showed normal skeletal muscle structure and function. However, the mice did have DM-related sleep issues, such as a higher number of REM sleep episodes and more REM sleep in general, leading to less restful sleep. In mice lacking MBNL1, another member of the MBNL protein family, the skeletal muscle effects were similar to what is seen in DM. But the central nervous system was not affected, according to Dr. Swanson. 

“What we would like to do now is identify the specific cellular events that are abnormal in the DM brain and see if there is something we can do to treat these disease manifestations with focused therapy development. We would also like to understand the heart and muscle problems in DM. We have developed mice with DM-associated problems and we want to use these mouse models to develop effective drug treatments. Also, we want to understand what is so different about the congenital form of DM. Why does it manifest in babies and children? If we can develop animal models for congenital DM, then we can begin to address the important question of what goes wrong during fetal life,” explains Dr. Swanson.

Recently, therapy development for DM has accelerated and treatments based on anti-sense oligonucleotides will hopefully enter clinical trials in the near future. These new studies focused on the roles of MBNL proteins in CNS function should lead to alternative therapeutic strategies designed to reverse effects caused by expression of the mutant DM1 and DM2 genes.

04/16/2013

Methylphenidate, a psycho-stimulant drug, also known by its 1948 trademarked name of Ritalin, could be useful in the treatment of excessive daytime sleepiness (EDS) for DM1 patients, according to a recent study conducted by The Department of Human Genetics at the Centre Hospitalier Universitaire de Quebec in Quebec City, Canada.  

A total of 24 French-Canadian patients who had DM1 and an Epworth Sleepiness Scale score of more than 10 (0-9: normal, 10-24: sleepy and medical advice should be sought) were invited to participate in the 3-week crossover trial of 20-mg/d of methylphenidate versus a placebo. There were two groups in the study; one group took the drug for 3 weeks, followed by a 2-week washout period, followed by 3 weeks of placebo, and the other group took placebo for 3 weeks, followed by a 2-week washout period, followed by 3 weeks of drug. Of the 24 patients (12 men; 12 women; median age 46 years), 17 completed the study. 

Patients’ Daytime Sleepiness Scale and the Epworth Sleepiness Scale, measured at the end of each 3-week period, were used to measure the effectiveness of methylphenidate as a treatment for EDS. The drug’s effectiveness was also determined by a mean sleep latency test, patients’ energy and vitality after the study, and patients’ moods. Tolerability to treatment was monitored by blood pressure, the results of an echocardiogram, and other lab tests. Adverse reactions to the treatment were based on patients’ reporting and were recorded at each visit to the clinic. 

The study concluded that a single 20-mg/d dose of methylphenidate significantly reduced daytime sleepiness in this small group of patients with DM1. The median scores on the Epworth Sleepiness Scale and the Daytime Sleepiness Scale showed a significant change. However, measurements of patients’ moods, energy, and vitality showed no changes, and the mean sleep latency test showed no significant changes. The most common adverse effects included nausea, loss of appetite, and palpitations, as reported by more patients who were treated with methylphenidate than by those receiving the placebo. Three patients stopped taking methylphenidate due to adverse effects that arose during treatment, which included diarrhea, nervousness and irritability. One patient died during the trial, but the autopsy results eliminated methylphenidate as the cause of death. 

01/23/2013