Monday, November 26, 2018

An anatomical locus for functional movement disorders

Maurer CW, LaFaver K, Limachia GS, Capitan G, Ameli R, Sinclair S, Epstein SA, Hallett M, Horovitz SG. Gray matter differences in patients with functional movement disorders. Neurology. 2018 Nov 13;91(20):e1870-e1879.


To explore alterations in gray matter volume in patients with functional movement disorders.

We obtained T1-weighted MRI on 48 patients with clinically definite functional movement disorders, a subset of functional neurologic symptom disorder characterized by abnormal involuntary movements, and on 55 age- and sex-matched healthy controls. We compared between-group differences in gray matter volume using voxel-based morphometry across the whole brain. All participants in addition underwent a thorough neuropsychological battery, including the Hamilton Anxiety and Depression Scales and the Childhood Trauma Questionnaire. To determine whether confounding factors such as comorbid depression, anxiety, or childhood trauma exposure contributed to the observed structural changes, nonparametric correlation analysis was performed.

Patients with functional movement disorders exhibited increased volume of the left amygdala, left striatum, left cerebellum, left fusiform gyrus, and bilateral thalamus, and decreased volume of the left sensorimotor cortex (whole-brain corrected p ≤ 0.05). Volumetric differences did not correlate with measures of disease duration or patient-rated disease severity.

This study demonstrates that patients with functional movement disorders exhibit structural gray matter abnormalities in critical components of the limbic and sensorimotor circuitry. These abnormalities may represent a premorbid trait rendering patients more susceptible to disease, the disease itself, or a compensatory response to disease.

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…

“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.”

t 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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