ARTICLE IN BRIEF
An international committee of movement disorders experts arrived, by consensus, at a new classification system of diagnosing dystonia — including clinical characteristics and etiology.
More than a hundred years after Hermann Oppenheim, MD, examined four young patients presenting with hypotonic muscle tone and tonic muscle spasm and coined the term “dystonia musculorum deformans,” and 30 years after neurologists arrived at a formal definition and means of diagnosing the disease, an international team of dystonia experts revamped the classification system and created a more inclusive description of the movement disorder. The group published the new guidelines in the July issue of Movement Disorders.
“The previous definition was not completely satisfying and we felt it needed expanding and other phenomenological aspects of the syndrome had to be mapped out,” said Anthony E. Lang, MD, professor and director of neurology at the University of Toronto. Dr. Lang is also director of the Edmond J. Safra Program in Parkinson's Disease at University of Toronto, and director of the Morton and Gloria Shulman Movement Disorders Centre at Toronto Western Hospital. “The new classification is designed to help clinicians go down the right diagnostic path.”
As with any consensus paper, not everyone agreed on the changes, he added. He said that clinicians who have been diagnosing dystonia may be more comfortable with the old terminology; but, he added, the new changes will help clinicians who don't know or understand the movement disorder “make a more definitive diagnosis. It will take experience in the clinic to see whether the new classification system falls short and needs further refining.”
The problem is this: Dystonia is classified as a syndrome and a symptom, and that has been confusing for the clinician, said Jonathan W. Mink, MD, PhD, professor of neurology, neurobiology & anatomy, brain & cognitive sciences, and pediatrics chief in the Division of Child Neurology and vice chair of neurology at University of Rochester Medical Center. What's more, he added, “the first formal classification in 1984 was in the pre-genetic era and a lot more information has come forward about dystonia. Nothing is ever permanent and there will be further refinements as we learn more.”
THE ORIGINAL DEFINITION
In 1911, when Dr. Oppenheim named the condition in his young patients he thought that it was partly a disease of muscle tone, hence the name dys (abnormal) and tonia (“hypotonic at one occasion and in tonic muscle spasm at another, usually, but not exclusively, elicited upon voluntary movements”).
It is not a disease of muscle tone, Dr. Lang explained. It is a movement disorder with some features that are shared among patients and some that vary. So how do clinicians lump all the features that are part of what neurologists call dystonia by a common phenomenon — involuntary, repetitive, and abnormal movements that can be triggered or worsened by voluntary actions? To make things more challenging, the symptoms can begin at any age and in different areas of the body — and the etiology has been linked to more than a dozen genetic mutations and other non-genetic causes. “It is a difficult disease to diagnose,” said Dr. Lang.
Involuntary, repetitive movements can include many independent conditions, such as blepharospasm, oromandibular dystonia, spasmodic dysphonia, and writer's cramp (hand dystonia), and it was at the first international symposium meeting in 1975 that clinicians advised lumping them altogether. Almost a decade later, in 1984, the Dystonia Medical Research Foundation brought together experts to develop a definition that clinicians could use to diagnose the condition. The definition was simple: a syndrome consisting “of sustained muscle contractions, frequently causing twisting and repetitive movements, or abnormal postures.”
As clinicians began to diagnose more cases, a classification system took hold. Stanley Fahn, MD, and Roswell Eldridge, MD, put together a classification system and published it in 1976. They split primary dystonia (with and without a familial pattern) and secondary dystonia, which meant that there were symptoms of dystonia as well as another neurological condition.
Drs. Fahn, C. David Marsden, and Donald B. Calne, went on to classify the condition into three axes: age of onset, distribution, and etiology. Changes continued as clinicians learned more about the disease. But it was confusing, which is why Alberto Albanese, MD, of the National Neurological Institute and the Catholic University in Milan, Italy, and colleagues spearheaded this latest level of changes.
“A classification system must be clinically useful and take into account what we know about the biological mechanisms so that researchers could also benefit from using it,” said Dr. Lang. “In recent years, a lot of genetic information has come forward, and trying to link it to the phenotypes seen in practice is challenging.”
One of the first things that required adjusting was the use of “primary” in describing pure cases of dystonia. It is now clear that many primary dystonia patients also have tremor and associated neurological and psychiatric problems beyond just the motor abnormalities. Clinicians have used “dystonia plus” when the patient has parkinsonism or myoclonus. Many clinicians are also confused when they should use “secondary dystonia.” There is also another term called heredodegenerative that is used to label a degenerative illness that may or may not have a familial link. The committee agreed that it has “limited value for understanding biological mechanisms and their potential relationships.”
Also, at issue with the older classification system was that it is not based on etiology but more phenomenology. Making more sense of these two lines of evidence, the experts said, would help in the diagnosis and in their decisions on what tests to order. Also, the new genetic findings — more than a dozen genes — add another complex layer to the diagnostic classification system.
The study authors thus redefine dystonia as “a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. Dystonic movements are typically patterned, twisting, and may be tremulous. Dystonia is often initiated or worsened by voluntary action and association with overflow muscle activation.”
Classification is important to figure out what kind of diagnostic testing needs to be ordered, and in determining prognosis and what types of therapy to use. The committee decided to cut the three axes into two, separating the list into clinical features and etiology. Under clinical characteristics, the clinician has a menu that includes age of onset, body distribution, temporal pattern, coexistence of other movement disorders, and other neurological symptoms. (See “Proposed Classification of Dystonia.”)
The second axis is etiology. To get a good handle on the cause, a detailed family history is essential and brain MRI scans to identify any anatomical changes, Dr. Lang said. (Genetic problems can also manifest in anatomical changes or acquired dystonia.) The classification system provides clinicians with a breakdown of genes that are known to cause dystonia and all possible causes of acquired dystonia. Genetic causes can be sporadic or familial.
The committee members know that the “loss of the traditional terms such as ‘primary,’ ‘plus,’ ‘heredodegenerative,’ etc., will inevitably lead to some discomfort,” they wrote in the Movement Disorders paper. “However, keeping these older terms for the sake of comfort will lead to a situation in which clinicians are left behind speaking an archaic language, while the scientific community making the inroads into advancing our knowledge moves on and adopts a language more suited for its purposes.”
“This will improve our approach to diagnosis and perhaps therapy too,” added Dr. Lang.
Mark Hallett, MD, chief of the Human Motor Control Section at the National Institute of Neurological Disorders and Stroke, another expert on the panel, agreed. “The old definition and classification were not adequate to deal with all of the new information on dystonia. The amount of information is enormous and it makes it difficult to understand what is going on. It helps the clinician and researchers organize knowledge better.”
“It used to be thought that if you had a phenomenology you could say what the etiology was,” Dr. Hallett added. “But a single etiology can produce multiple syndromes. It is not a one-to-one match.”
“I do think that clinicians will use it,” said Mahlon R. DeLong, MD, professor of neurology at Emory University in Atlanta, and another member of the consensus committee. “It doesn't break new ground but it is un-muddying the waters. We'll have to wait and see.”
Cynthia L. Comella, professor in the department of neurological services at Rush University Medical Center, was not involved with the panel, said that, as a dystonia expert, the classification system “will solidify the way we look at dystonia. Right now, a lot of clinicians in the field use their own terms. This provides us with a framework to communicate using the same terms. We need this type of consistency. It will certainly be modified in the future but it is a great start.”
C. Warren Olanow, MD, a professor of neurology and neuroscience at Mount Sinai School of Medicine in New York, said that he is not sure whether the new classification will ultimately help clinicians. He is the co-editor of MovementDisorders and was not involved in the consensus plan either. “In the future, classification will not be phenomenological. We will define disease by the causes. There is tremendous variability between genotype and phenotype. The days of description that add to medicine are largely over.”
Dr. Lang counters: “Etiological diagnosis is clearly critical to advances in the future, however, accurate clinical classification and recognition will be equally important. If the clinical characterization and diagnosis is erroneous, interpretation of abnormal test results or research findings, for example a genetic test or novel imaging or electrophysiological study, could be extremely misleading and potentially damaging to both the individual patient and to scientific advancement.”
LISTEN IN: Experts on dystonia teamed up to bring an old definition and a classification system up to date. Anthony Lang, MD, a movement disorders specialist at the University of Toronto, talks to Neurology Today about the new consensus report — what they changed, what they kept in, and why — to make the diagnosis of dystonia more accurate: http://bit.ly/rCBryX.