Focus on Functional Neurological Disorders

Within the behavioral neurology division at the Massachusetts General Hospital, Dr. David Perez, a board certified neurologist and psychiatrist, cognitive-affective neuroscientist and neuroimaging researcher, has established a new clinical and research initiative in Functional Neurological Disorders (FND). Patients with FND come to the clinic experiencing seizure-like events, abnormal movements, limb weakness and/or gait difficulties, yet traditional neurologic investigations don’t find a medical explanation for these symptoms. Doctors don’t see primary disruptions in motor brain pathways in these patients, nor do they uncover evidence of electrical seizures. Patients with these poorly understood functional neurological symptoms make up approximately 16 percent of referrals to neurology clinics. “These conditions are not rare. There’s a real unmet need,” says Dr. Perez. “By and large, experts in other neurologic and psychiatric conditions are ill-equipped as to how to help this group of patients.”

During an initial consultation at the FND clinic, Dr. Perez provides patients with concurrent neurological and psychiatric consultations. Working closely with colleagues in neuropsychiatry, neuropsychology, psychology, physical therapy, social work and the comprehensive neurology, epilepsy and movement disorder divisions, he develops an integrated and individualized “patient-centered” treatment plan that may involve physical therapy, cognitive behavioral therapy, or pharmacology, particularly if the patient is experiencing mood or anxiety symptoms. “Many patients come in worried that they will not be heard,” says Dr. Perez. “At our clinic, they learn that FND is a real neuropsychiatric condition, and if they meet the criteria, we provide a clear diagnosis.”

In parallel with the founding of the FND clinic, Dr. Perez established the Mass General Functional Neurology Research Group with a goal to use psychometric and other clinical characterization tools alongside advanced structural and functional magnetic resonance imaging (MRI) methods to identify clinical and neuroimaging biomarkers of symptom severity, prognosis and treatment response across the spectrum of FND. Patients who join the Mass General FND Clinical Research Cohort participate in longitudinal follow-up visits to collect additional psychometric data that will help the researchers learn who is responding to treatment and who is not.

The clinic and research group are unique in that they welcome patients with a wide range of functional symptoms. Traditionally, patients with psychogenic non-epileptic seizures would see an expert in epilepsy, while a patient with functional movement disorders might see a different specialist, and patients with limb weakness or gait troubles still other experts. The FND clinic’s novel, comprehensive approach pools resources for these patients and also recognizes that patients with FND may have commonalities despite their range of symptoms.

For instance, early research suggests that cortical hubs, regions of the brain where emotional, sensory, cognitive and motor information converge, may be the seat of disruptions that result in FND symptoms. More research is necessary, so Dr. Perez and his research group are following up with comprehensive neuroimaging in collaboration with colleagues at the Mass General/ Harvard-MIT Division of Health Sciences and Technology (HST) Athinoula A. Martinos Center for Biomedical Imaging. “Our research group is dedicated to understanding the biology of this very poorly understood neuropsychiatric condition,” says Dr. Perez.

The neuroimaging research includes the application of quantitative structural neuroimaging techniques to characterize brain structure alterations across the spectrum of FND. Imaging methods include cortical thickness, voxel-based morphometry and diffusion tensor imaging analyses. In parallel, the ongoing collection of Blood-Oxygen-Level-Dependent resting-state functional connectivity data will reveal functional alterations that may contribute to the understanding of FND. Future investigations will couple clinical and neuroimaging characterizations with treatment modalities to specifically investigate neural mechanisms and biomarkers of treatment response.