Early phase of a seronegative autoimmune psychosis with increased kappa free light chains

Introduction: Autoimmune psychosis is often misinterpreted as schizophrenia. Intrathecal immunoglobulin G (IgG) synthesis is regarded as an important link to an inflammatory process within the central nervous system (CNS). We describe here a case in which a patient with seronegative autoimmune psychosis was diagnosed with increased local kappa free light chains (FKLC) in his cerebrospinal fluid (CSF) indicating an early manifestation of autoinflammation within the CNS.

Methods: A 20-year-old student presented with acoustic hallucinations as dialogical and imperative voices as well as fatigue, difficulty concentrating and memory problems for the last two to three years but experiencing acute exacerbation in the few weeks prior to admission. He also reported sensory phenomena such as heightened smell sensitivity and déja-vu-sensations. We carried out these examinations: laboratory testing, cranial magnetic resonance imaging (cMRI), neuropsychological testing, electroencephalographic (EEG) and sleep deprivation EEG, CSF analysis assessing FKLC, and cranial fluorodesoxyglucose emission tomography (FDG-PET-CT).

Results: The laboratory tests and cMRI revealed nothing remarkable. Neuropsychological testing, however, revealed increased distractibility, deficits in attention and executive functions and significant verbal memory impairments. An EEG and sleep deprivation EEG revealed bifrontotemporal Theta and Delta wave slowing. CSF analysis revealed no autoantibodies, but an increased FKLC synthesis (41,7%). A cerebral FDG-PET showed a bilateral mesiotemporal hypometabolism. We diagnosed autoimmune psychosis and started methylprednisolone intravenously in addition to antipsychotic treatment with olanzapine. Our patient exhibited a reduction in psychotic symptoms several weeks later.

Conclusions: We assumed a seronegative autoimmune psychosis due to a subacute deterioration of psychotic symptoms in conjunction with memory disturbances and sensory phenomena. Furthermore, the bitemporal hypometabolism in FDG-PET and increased FKLC in the CSF support an early phase of an autoimmune process. Immunotherapy led to an alleviation of symptoms, supporting our diagnosis of an autoimmune psychosis. To our knowledge this is the first case providing evidence of a seronegative autoimmune psychosis, thus highlighting need for CSF analysis in conjunction with psychotic disorders as a crucial diagnostic approach.