Neurobiology of Psychogenic Movement Disorder and Non-Epileptic Seizures

This study is part of a series of studies that will explore how the mind and the brain work to cause episodes of uncontrollable shaking in people who have no known underlying brain or medical disorder. The study is conducted at NIH and at the Brown University Rhode Island Hospital.

Healthy volunteers and people with psychogenic movement disorders (PMD) or non-epileptic seizures (NES) who are 18 years of age or older may be eligible for this study.

Patients with NES have 3 teaspoons of blood drawn. The blood is tested for two genes that are normally found in healthy individuals to see if they are found more frequently in patients with uncontrolled shaking.

Patients with PMD have blood drawn for testing and also undergo functional magnetic resonance imaging (fMRI) to look at how the brain functions while the subject performs a specific task. MRI uses a strong magnetic field and radio waves to obtain images of body organs and tissues. During the scan, the subject lies on a table that can slide in and out of the scanner, a metal cylinder. The scan lasts about 60 to 90 minutes, during which the subject may be asked to lie still for up to 10 minutes at a time and to perform tasks, such as identifying the gender of faces shown on a screen.

Healthy volunteers may have blood drawn for genetic testing or fMRI or both.

Objectives:

The study investigates the neurobiological correlates of conversion disorder (CD). The primary objectives are to investigate in CD patients:

• The role of emotional valence in an implicit emotional processing task (COMPLETE)
• The frequency of the 5HTTLPR S/S genotype
• Structural differences in grey matter of the brain as detected by voxel-based morphometry (VBM)

Exploratory objectives are to investigate in CD patients:

• The frequency of several gene polymorphisms that are implicated in stress and affective disorder, including 5HTTLPR S/S (serotonin receptor), COMT (catechol-o-methyltransferase enzyme), and Val/Met BDNF (brain-derived neurotrophic factor) genotypes, as well as other polymorphisms or mutations to be determined later.
• The levels of salivary cortisol as a measure of stress.
• The heart rate variability, as a measure of autonomic nervous system function.
• Structural differences in white matter of the brain as detected by diffusion tensor imaging (DTI)
• The resting state BOLD fMRI signal

Study population:

We intend to study adult patients with diagnoses of psychogenic movement disorders (PMD) seen by the Human Motor Control Section clinic (HMCS), patients with diagnoses of psychogenic non-epileptic seizures (PNES) seen by the Epilepsy clinic and healthy volunteers. The PNES patient group will include patients seen at Rhode Island Hospital.

Design:

An assessment for psychiatric diagnoses and measurement scales will be administered to the PMD and PNES patients, and healthy volunteer controls.

• Functional MRI (fMRI): emotional processing will be studied using a gender identification task with differing emotional valences. (COMPLETE) Resting state BOLD fMRI signal will also be obtained.
• Anatomical MRI: VBM and DTI will be performed using anatomical MRI sequences collected during the fMRI scanning or subsequent dedicated anatomical MRI sessions
• Genetics: blood will be collected for testing.
• Stress biomarkers: saliva will be collected for testing.
• Autonomic nervous system function: electrocardiogram (EKG) will be obtained to determine heart rate variability.

Outcome measures:

• fMRI study: blood oxygenation level dependent (BOLD) signal in the regions of interest during a gender identification task (primary) [COMPLETE] as well as resting state BOLD signal (exploratory)
• Anatomical MRI: VBM (primary) and DTI (exploratory)
• Genetics: (a) S/S genotype of the serotonin transporter promoter region polymorphism. (primary) (b) Polymorphism frequency of several genes related to affective disorders and/or stress (exploratory)
• Stress biomarkers: salivary cortisol levels (exploratory)
• Autonomic nervous system function: heart rate variability as measured by EKG (exploratory)
• Psychological profile scales: scores exploratory

• Psycogenic Movement Disorders
• Non-Epileptic Seizures

• Williams DT, Ford B, Fahn S. Phenomenology and psychopathology related to psychogenic movement disorders. Adv Neurol. 1995;65:231-57. Review. No abstract available.
• Carson AJ, Ringbauer B, Stone J, McKenzie L, Warlow C, Sharpe M. Do medically unexplained symptoms matter? A prospective cohort study of 300 new referrals to neurology outpatient clinics. J Neurol Neurosurg Psychiatry. 2000 Feb;68(2):207-10.
• Feinstein A, Stergiopoulos V, Fine J, Lang AE. Psychiatric outcome in patients with a psychogenic movement disorder: a prospective study. Neuropsychiatry Neuropsychol Behav Neurol. 2001 Jul-Sep;14(3):169-76.

• INCLUSION AND EXCLUSION CRITERIA:

Inclusion and exclusion criteria

General inclusion criteria for PMD patients:

• Diagnosis of clinically definite PMD utilizing Fahn and Williams criteria. The diagnosis must be made by a neurologist
• Able to give informed consent
• Age 18 or older

General inclusion criteria for PNES patients:

• Diagnosis of PNES based on recording of patient's typical episode during 24 h video-EEG without concomitant EEG changes. The diagnosis must be made by a neurologist.
• Able to give informed consent
• Age 18 or older

General exclusion criteria for PMD patients:

• Significant neurological disorders (primary or comorbid) such as neurodegenerative disorders, stroke, movement disorders or epilepsy
• Inflammatory disorders or autoimmune disorders active within the last 6 months
• Patients with psychotic disorders or manic depression or active substance abuse within the last 6 months
• Current suicidal ideation
• Disease severity requiring inpatient treatment

Additional exclusion criteria for PMD patients for MRI:

• Patients with movement symptoms at rest that may substantially inhibit resolution, comfort, or safety of MRI
• Previous history of or MRI findings consistent with brain tumors, strokes, trauma or arterial venous malformations
• History of traumatic brain injury with loss of consciousness or amnesia lasting greater than a few seconds
• Contraindication to MRI
• Pregnancy
• Significant medical illness
• Patients with current post-traumatic stress disorder, panic disorder or obsessive compulsive disorder
• Patients on tricyclic antidepressants or antiepileptic medications 2 weeks prior to testing

General exclusion criteria for PNES patients:

• Significant neurological disorders (primary or comorbid) such as neurodegenerative disorders, stroke, movement disorders or epilepsy
• Inflammatory disorders or autoimmune disorders active within the last 6 months
• Patients with psychotic disorders or active substance abuse within the last 6 months
• Current suicidal ideation
• Disease severity requiring inpatient treatment

Inclusion criteria for healthy volunteers:

• Able to give informed consent
• Age 18 or older

Exclusion criteria for healthy volunteers:

-General exclusion criteria for healthy volunteers:

• Significant neurological disorders (primary or comorbid) such as neurodegenerative disorders, stroke, movement disorders or epilepsy
• History of DSM IV-defined schizophrenia, schizoaffective disorder, bipolar disorder or major depression with psychosis
• History of psychotic disorders or manic depression or active substance abuse within the last 6 months
• Subjects with post-traumatic stress disorder, obsessive compulsive disorder or panic disorder
• Subjects on antidepressants or antiepileptic medications
• Inflammatory disorders or autoimmune disorders active within the last 6 months

Additional exclusion criteria for healthy volunteers for MRI:

• Previous history of or MRI findings consistent with brain tumors, strokes, trauma or arterial venous malformations
• Contraindication to MRI
• Pregnancy
• Significant medical illness

Specific Exclusion Criteria for all subjects for HRV:

• You take medications that affect your heart rate or rhythm
• You have a history of heart disease