Association of ADHD symptoms, pain, and tics with anti-thalamus antibodies in cerebrospinal fluid

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Introduction Complex mixed presentations of severe mental disorders (SMD) with treatment resistance pose major challenges in clinical practice. The role of novel neuronal antibodies in cerebrospinal fluid (CSF) is largely unexamined in this context. Methods A well-studied paradigmatic case of a 36-year-old female patient is reported. Results She presented with attention-deficit/hyperactivity disorder-like symptoms (including frequent sensory overload), severe pain (pre-diagnosed as fibromyalgia and somatoform pain disorder), and motor tics. In addition, she developed secondary depressive symptoms. Various psychopharmacological treatment attempts were unsuccessful or not tolerated. The diagnostic routine work-up with a wide range of blood tests, electroencephalography (EEG), routine magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analyses, and [18F]fluorodeoxyglucose positron emission tomography revealed no clear pathological findings. Tissue-based assays using CSF material found strong immunoglobulin G antibody staining specifically directed against a cell population in the thalamus. Neurotransmitter measurements detected low GABA, glutamate and serotonin concentrations as well as high dopamine levels in the CSF. Different MRI-based analyses indicated no neurostructural alterations in the thalamus; however, left mesiotemporal volume loss was identified. The independent component analysis of the EEG showed left temporal theta waves, partly resembling spike-wave-complexes. Immunotherapy using high-dose steroids resulted in a partial improvement with subjectively reduced stimulus overload, intermediate disappearance of pain, and fewer tics. The improvement could not be objectified psychometrically/neuropsychologically. The mesiotemporal volume loss was no longer present. There were no relevant changes in further research MRI measurements of the thalamus including arterial spin labeling, diffusion tensor imaging, and diffusion microstructure imaging from pre to post-immunotherapy. Discussion Novel antibodies against strategic brain structures, such as the thalamus, might be associated with some complex SMD. Further immunopsychiatric research in this direction holds promise for a better understanding of similar patients.

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