Diagnostic Odyssey of Patients with Myotonic Dystrophy, Journal of Neurology, 2013

Published on Thu, 08/22/2013

Researchers from the University of Rochester recently summarized the “diagnostic odyssey” experienced by a group of 814 individuals with myotonic dystrophy enrolled in their national registry.  They focused on individuals with a confirmed diagnosis and with first symptoms starting after more than 4 weeks of age, and collected the age when the first symptom was observed, the type of symptom first experienced, any misdiagnoses, the age when a correct diagnosis was made, and the diagnostic tests administered.

This study found that members with myotonic dystrophy type 1 (DM1) experienced an average of 7 years delay to diagnosis, and members with myotonic dystrophy type 2 (DM2) had an even more stunning delay of 14 years to get a correct diagnosis.  On average, DM1 individuals experienced their first symptoms at age 26, whereas DM2 individuals had a later average age of onset at 34 years old.  In general, one quarter of the study’s myotonic dystrophy population experienced their first symptom before the age of 18.

Researchers determined that the type of symptom that manifests first can help dictate how quickly it will take for a correct diagnosis for DM1.  In DM1, members who reported weakness as their first symptom waited on average 6.6 years for their diagnosis, whereas a significantly longer delay in diagnosis was found when the first symptom was myotonia (7.6 years), fatigue (11.5 years), and sleep disturbance (15.6 years).  In DM2, a proper diagnosis was delayed on average 7 years, and was not significantly changed based on the type of symptom first observed.  The most common first symptom in DM1 was grip myotonia, followed by arm weakness, general weakness and leg weakness.  The most common first symptom in DM2 was leg weakness, followed by grip myotonia, general weakness and arm weakness.

Given that members with DM2 waited much longer for a correct diagnosis, the researchers further examined what caused the delay.  One quarter of DM2 members had an incorrect diagnosis, most often originating from a neurologist.  The most common misdiagnosis was limb-girdle muscular dystrophy, but others included chronic fatigue, fibromyalgia, arthritis, and multiple sclerosis.  DM2 members also underwent significantly more testing than DM1 members, having more EMGs, muscle biopsies and genetic testing.  Overall, 71% of DM2 members in this study had a confirmed genetic diagnosis, compared to 58% of DM1 members.

The authors stressed the need for a timely diagnosis to facilitate addressing the short term medical needs of people with DM, because many of the symptoms are disabling and reduce quality of life.  They also note that it is “imperative to diagnose patients earlier in the disease course if promising experimental therapies can reverse or delay onset of symptoms and potentially ward off the progression of many disabling manifestations”.  Now that genetic diagnoses have been available for DM1 and DM2 since 1992 and 2001, respectively, and much effort is being put into educating the community and medical trainees about DM, hopefully the diagnostic odyssey for people with DM will be improved.

An abstract of the original article can be found here.



Key DM Research Discoveries

Published on Fri, 07/26/2013

Timeline of key discoveries in myotonic dystrophy research since DM was first described in 1909. Click on the corresponding timeline entry for links to research abstracts or reviews. 

Abstracts not available for: Greenfield and Fleischer, 1911/1918; Bell, 1947; Vanier, 1960.



Impact of Childhood and Congenital DM on Quality of Life

Published on Tue, 06/25/2013

Nicholas Johnson, MD, and researchers at the University of Rochester recently published an article in The Journal of Child Neurology that describes the impact of childhood and congenital myotonic dystrophy on quality of life. The authors interviewed 21 children with childhood and congenital myotonic dystrophy and 13 parents. After recording these interviews, the authors reviewed transcripts to identify the most important symptoms to parents and children. Overall, participants reported 189 different symptoms. 

Dr. Johnson and his colleagues found that many of the parents and children identified trouble speaking (dysarthria) as the primary symptom that impacted the children’s lives. Other participants identified learning difficulties and problems concentrating as life altering symptoms. Although many of the study participants did not identify a diagnosis of autism specifically, autistic traits, such as a narrow scope of interest, repetitive speech, inappropriate social responses, and inflexibility were reported. 

As expected, many of the symptoms affecting those with congenital and childhood myotonic dystrophy are different from the symptoms of adult-onset myotonic dystrophy type-1. Prior work by Chad Heatwole, MD, MS-CI, the senior author on this study, identified fatigue, hand and finger weakness, and difficulty walking as significantly impacting the quality of life of those with adult-onset myotonic dystrophy type-1. While these symptoms were also reported in children with myotonic dystrophy, their presentation and significance were different. 

Importantly, many symptoms of congenital and childhood myotonic dystrophy, such as communication difficulties, already have available treatments. The authors hope that by identifying the wide range of symptoms affecting children with myotonic dystrophy, doctors will be able to identify critical symptoms earlier and initiate timely treatment strategies.

Dr. Johnson and University of Rochester researchers, with the support of MDF, have used information from this study to develop a survey, which was distributed to US, Canadian and Swedish patients with congenital and childhood myotonic dystrophy. Results from this international group of patients will be used to further define and prioritize the most important symptoms to patients with congenital and childhood myotonic dystrophy. Ultimately this data will be used to help guide researchers in designing future therapeutic trials for these populations. 


Ritalin Could Curb Excessive Daytime Sleepiness

Published on Wed, 01/23/2013

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. 

For more information about this study, click here


Mexiletine for Myotonia: A New Use for an Old Heart Drug?

Published on Tue, 10/23/2012

A generic cardiovascular drug called mexiletine, initially developed to treat heart rhythm abnormalities, appears to hold some potential for treating muscle stiffness and other symptoms of non-dystrophic myotonias (NDMs), a rare group of disorders without progressive muscle wasting and weakness, that have abnormalities in the function of ion channels in the muscle cells (chloride or sodium channels).  The abnormal ion channel function leads to stiffness and delayed relaxation of muscle following grip or tight closing of the eyes (myotonia).  Myotonic dystrophy (DM) has as one of its alterations abnormal function of the chloride channel.  This causes myotonia and stiffness, and, like the patients with non-dystrophic myotonia, DM patients show a beneficial response to treatment with mexiletine.

A study published in the Journal of the American Medical Association (JAMA) in early October evaluated the drug in 59 people with NDMs. The study, sponsored by the National Institutes of Health’s Rare Disease Clinical Research Network, randomized patients with one of the rare forms of non-dystrophic myotonia to either the study drug (one capsule of mexiletine three times a day for four weeks) or placebo. After four weeks, patients stopped taking either for a week then switched to the opposite treatment for four weeks. 
When patients took the study drug, their muscle stiffness improved up to 40 percent and their pain scores fell by 17%. Objective tests also found that mexiletine reduced abnormal electrical activity (myotonic discharges) in the muscles that led to the spasms and stiffness. Patients also experienced significant improvements in their overall quality of life. The most common side effects were gastrointestinal, such as diarrhea, nausea, and heartburn. Click here to read an abstract of the article.
This study echoes findings on mexiletine and its beneficial effects on myotonia published in 2010 by Drs. Moxley, Logigian, Martens, Thornton et al.  The 2010 study, conducted at the University of Rochester with a group of 20 DM1 patients, found that grip relaxation time improved by 50% and muscle stiffness decreased when patients took mexiletine compared to placebo. Click here to read an abstract on the 2010 Rochester study.
Mexiletine works by slowing the rate of movement of sodium ions into muscle cells, reducing or eliminating the tendency of the muscle to maintain a prolonged contraction.  This enables the muscle cell to relax properly and be ready for the next contraction.  Mexiletine works for several hours and it needs to be taken two or three times daily to exert continued beneficial effects.
The drug is not approved for treating either NDM or DM, but doctors can prescribe it “off label.” However, as with any drug, there are risks and benefits and only your doctor, with your input, can decide if it might work for you.