Obsessive-compulsive symptoms and inflammatory brain changes detected using an innovative multimodal diagnostic work-up.

INTRODUCTION: Obsessive-compulsive disorder (OCD) is associated with a dysfunction of the cortico-striato-thalamo-cortical loops and overarching functional networks as well as with disturbances in serotonin, dopamine, and glutamate neurotransmission. In rare individual cases, the underlying cause is an autoimmune OCD. Innovative multimodal diagnostic work-ups can support the identification of mild neuroinflammation in clinical practice as shown in the present paradigmatic case.

CASE STUDY: Susceptibility-weighted magnetic resonance imaging (MRI) of a 28-year-old female patient with severe OCD revealed a left thalamic microbleed. Subsequent diffusion tensor imaging tractography showed that the thalamus microbleed involved centro-thalamic and some fronto-thalamic fibers. A comparison of the patient's diffusion microstructure imaging (DMI) results with those of a matched healthy control group revealed widespread alterations in cerebral microstructure. Elevated free fluid in left temporal regions and relative cortical cellular loss were observed, compatible with an inflammatory process in terms of edematous changes. The frontal regions displayed an increase in the extracellular compartment accompanied by a decrease of the dendritic structures. [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) showed a slightly lower cortical FDG metabolism of the right hemisphere, most likely within the physiologic range. Electroencephalography identified electrophysiological abnormalities with intermittent rhythmic slowing, and a tissue-based assay on unfixed mouse brain slices found finely dotted binding of cerebrospinal fluid immunoglobulin G autoantibodies against nuclear antigens (ANAs). With guideline-compliant treatment and vitamin D supplementation, great clinical improvement and markedly reduced microstructural DMI alterations in MRI were achieved in the follow-up after about half a year.

DISCUSSION: This case study illustrates how advanced multimodal diagnostics can contribute to a better pathophysiological understanding of OCD with a frontal disconnection and further mild neuroinflammatory changes. An underlying autoimmune cause was supported by the detection of intrathecal autoantibodies against nuclear antigens. ANA-associated diseases, such as neuropsychiatric lupus, have previously been associated with microbleeds. Deep clinical phenotyping approaches could assist in establishing precision medicine approaches for OCD.