Abrupt Termination of Severe Treatment Refractory Neuropsychiatric Symptoms in a Patient Treated With Rituximab-A...

A 65-year-old woman presented to a joint rheumatology, neurology, and psychiatry clinic with subacute onset of severe neuropsychiatric symptoms that began 2 years prior. The symptomatology had been dominated by paranoid ideation, withdrawal from family, and cognitive changes. Over the previous 2-year period the patient required inpatient psychiatric care three times with provisional diagnoses, including major depressive disorder with psychotic features, schizophrenia, and late-onset schizophrenia. Pharmacologic treatments consisted of multiple trials of different antidepressants and antipsychotics, eventually with a trial of clozapine without notable benefit and further worsening of symptoms. Ultimately the patient was unable to perform her activities of daily living (ADL) independently. Past medical history was notable for pernicious anemia. An extensive evaluation was notable for antibodies to intrinsic factor consistent with pernicious anemia and low-titer antiphospholipid antibodies. Magnetic resonance imaging (MRI), electroencephalography (EEG), and cerebrospinal fluid (CSF) evaluations were all unrevealing. Neuropsychologic testing demonstrated difficulties with executive function and semantic retrieval along with ADL deficits meeting criteria for major neurocognitive disorder (MNCD) of uncertain etiology. A multidisciplinary evaluation ultimately identified a possible systemic lupus erythematosus (SLE)-related process. The patient received two 1-g infusions of rituximab. Approximately 3 weeks later she experienced a substantial reduction in her complex neuropsychiatric symptoms, and within 6 months she almost completely returned to her premorbid level of functioning. This case illustrates an atypical presentation of treatment-resistant neuropsychiatric and neurocognitive symptoms that benefitted from comprehensive, multidisciplinary evaluation and treatment. When frank antibody-positive autoimmune encephalitis and antibody-negative autoimmune encephalitis have been excluded, clinicians should consider underlying emerging systemic autoimmune disease, for example, SLE as a potential cause of psychosis and other severe neuropsychiatric manifestations, prompting further diagnostic workup and treatment strategies, including immunotherapy.