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Disease Mechanisms

Structural Gray Matter Abnormalities Identified Patients with Functional Movement Disorders Is It Reason Enough to Treat in Neurology?

Shaw, Gina

doi: 10.1097/01.NT.0000549646.17747.7b
Disease Mechanisms
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ARTICLE IN BRIEF

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Researchers found that patients with functional movement disorders had structural gray matter abnormalities in components of the limbic and sensorimotor circuitry.

Functional movement disorders (FMDs) — abnormalities of movement such as spasms, shaking, or jerks of the face, neck, trunk, or limbs that are not attributable to known neurologic disease — are among the most common presenting conditions in neurologic practice. A 2010 study in Clinical Neurology and Neurosurgery suggests that they make up approximately 15 percent of new referrals to neurologists, second only to headache.

And yet, because they are apparently not associated with alterations in the nervous system that can be recognized by standard testing, functional movement disorders have long been a condition in search of a clinical home.

“Because there has been no identifiable brain abnormality or other clear localization for these patients' problems, neurologists have tended to categorize them as psychological,” said Michele Tagliati, MD, FAAN, Caron and Steven D. Broidy Chair for Movement Disorders at Cedars-Sinai Medical Center in Los Angeles. “Psychiatrists are not that interested in these conditions because the patient is not usually severely depressed or an immediate threat to himself, and not amenable to typical psychiatric therapies. So these poor people often fall through the cracks between two specialties.”

Indeed, functional movement disorders have a generally poor prognosis, with one 2014 systematic review in the Journal of Neurology, Neurosurgery, and Psychiatry finding that 39 percent of patients are the same or worse on long-term follow-up, with high levels of physical disability and psychological distress.

“All neurologists have seen these cases, and they take up a tremendous amount of time and energy, because they are hard to treat and cause a lot of distress,” said David Standaert, MD, PhD, FAAN, John N. Whitaker professor and chairman of neurology at University of Alabama at Birmingham.

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EVIDENCE OF GRAY MATTER ABNORMALITIES

In recent years, however, functional neuroimaging studies have identified neural network abnormalities in patients with these conditions. Tracing these abnormalities to structural abnormalities in the brain has proven more difficult. But in a new paper appearing in the October 10 online edition of Neurology, a multicenter group of researchers has, for the first time, identified specific gray matter changes in a group of such individuals.

“These abnormalities may represent a premorbid trait rendering patients more susceptible to disease, the disease itself, or a compensatory response to disease,” wrote the authors, led by Carine Maurer, MD, PhD, clinical assistant professor of neurology at Stony Brook University School of Medicine and including investigators from the National Institute of Neurological Disorders and Stroke, the National Institute of Mental Health, Georgetown University, and the University of Louisville. The study is the largest to date examining gray matter structural changes in patients with functional movement disorders.

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The observational study included a group of 48 patients with FMDs along with 55 matched healthy controls. The study authors hypothesized that patients would exhibit altered gray matter volume when compared with controls. The average disease duration was 5.9 years, and patients' self-reported abnormal movements included tremor (75 percent), jerking movements (65 percent), abnormal gait/balance (71 percent), abnormal speech (50 percent), abnormal posturing/dystonia (35 percent), and paresis (35 percent). The majority of patients (77 percent) had bilateral or non-lateralizing symptoms, while 17 percent had right-lateralizing symptoms, and 6 percent had left-lateralizing symptoms.

All study participants underwent T1-weighted structural magnetic resonance imaging (MRI), as well as a thorough neuropsychological battery, including the Hamilton Anxiety and Depression scales and the Childhood Trauma Questionnaire. The investigators found differences in gray matter volume in critical components of the limbic and motor circuitry. Specifically, patients with functional movement disorders exhibited greater gray matter volume in the left amygdala, left caudate, left putamen, left cerebellum, left fusiform gyrus, and bilateral thalami, while gray matter volume in the left sensorimotor cortex was reduced.

“These findings are noteworthy as they provide important evidence that FMD patients possess not only altered functional brain connectivity, as previously described, but also structural alterations that are not readily identifiable on routine clinical brain MRI,” the authors note.

The study also provided evidence that differences in gray matter volume in FMDs are not linked to underlying psychiatric conditions. “With the exception of two weak correlations between volumetric differences and psychometric scores, our analysis failed to detect significant associations between anxious or depressive symptoms and alterations in GMV [gray matter volume],” the authors noted.

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EXPERT COMMENTARY

“This really is the first paper to clearly tell us that the term ‘functional’ is not entirely representative of these disorders, that the brain itself may have structural alterations,” said Alberto Espay, MD, FAAN, professor and endowed chair of the James J. and Joan A. Gardner Center for Parkinson's Disease at the University of Cincinnati. “What it doesn't tell us, of course, because it's a cross-sectional study, is whether the structural brain changes preceded the onset of the abnormal movements, have developed as part of treatment, or are indeed a result of the overall progression of the disease. We don't know which is the chicken and which is the egg here.”

While the study opens up new possibilities for research, however, he noted that it will not necessarily lead to immediate major changes in how FMD patients are diagnosed in clinical practice. “Their findings are a composite of multiple measures, and because of the nature of the analysis, rely on a lot of patient data,” he said. “That is not particularly useful on an individual level to tease out what might be going on with a specific patient.”

“This technology is not something that can be readily used for differential diagnosis in Dr. Smith's office tomorrow,” Dr. Tagliati agreed. “And at the end of the day, even if someone comes to your office with something they have been told is psychogenic and you find abnormalities on these fancy imaging studies, I'm not sure what you're going to do with that.”

But he added that while the study does not provide an immediate new treatment or strategy from the clinician, it does help to move the field away from older, paternalistic psychoanalytic explanations. “I am certain that these authors will follow up with more in-depth research on an even larger population. This is an important first step toward the understanding of what has been in some cases a very mysterious phenomenon.”

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It also provides strong evidence to neurologists that treating these disorders does lie within their purview. “FMDs are associated with structural abnormalities in the brain, which leads you to the idea that you can't dismiss these, even though they are not in the conventional neurologic disease model,” Dr. Standaert said.

“Clinically definite functional movement disorders can really only be identified in the rearview mirror — if you approach them as such, and they get better. We do know that these disorders respond to physical therapy, rehabilitation measures and in some cases cognitive behavioral therapy. You don't necessarily need to reach for the prescription pad, but if you can refer the patient to a therapist who will approach their condition as a disorder of movement, treatment can often be very successful.”

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LINK UP FOR MORE INFORMATION:

•. Maurer CW, LaFaver K, Limachia GS, et al Gray matter differences in patients with functional movement disorders http://n.neurology.org/content/early/2018/10/10/WNL.0000000000006514.full.pdf. Neurology 2018; Epub 2018 Oct 10.
    •. Stone J, Carson A, Duncan R. Who is referred to neurology clinics? The diagnoses made in 3781 new patients https://linkinghub.elsevier.com/retrieve/pii/S0303-8467(10)00171-X. Clin Neurol Neurosurg 2010; 112(9):747–751.
    •. Gelauff J, Stone J, Edwards M, Carson A. The prognosis of functional (psychogenic) motor symptoms: A systematic review https://jnnp.bmj.com/content/85/2/220.long. J Neurol Neurosurg Psychiatry 2014;85 (2):220–226.
    © 2018 American Academy of Neurology