Psychiatric phenomena as initial manifestation of encephalitis by anti‐NMDAR antibodies

Abstract

Objective: Autoimmune encephalitis associated with autoantibodies against the N -methyl-d-aspartate receptor (NMDAR) often presents with behavioural change. Our objective was to describe in detail the psychiatric presentation and pathways to care in order to aid the early diagnosis of NMDAR encephalitis. Methods: Sera and cerebrospinal fluid (CSF) from patients with suspected NMDAR encephalitis were tested on HEK 293 cells transfected with the NR1 subunit of the NMDAR. Clinical information was obtained from the referring psychiatrists and neurologists and by review of the clinical records. Results: Samples from 15 patients (13 female, 2 male, mean age 24 years, range 5-56 years) tested anti-NMDAR positive. Twelve of the 15 patients (80%) presented with prominent psychiatric symptoms and 8 were initially referred to a psychiatric service. The most prominent initial psychiatric symptoms were anxiety in seven (47%), behavioural change (often bizarre) in six (40%) and agitation in five (33%). All patients developed psychiatric symptoms in the first 6 weeks of illness. Thirteen patients received psychotropic medications: antipsychotics in 12 and benzodiazepines in 11. Treating physicians considered the psychotropic medication not effective in 11 patients resulting in many drug switches. At nadir, all patients were in a very poor condition. However, eight patients (53%) recovered (almost) completely. Outcome tended to be better in patients who had received early immunotherapy or tumour removal. Conclusions: Autoimmune encephalitis and anti-NMDAR testing in serum and CSF should be considered in patients, especially young females, presenting with atypical psychiatric phenomena. Early diagnosis and treatment will likely improve the prognosis of NMDAR encephalitis. Significant outcomes• In this first Dutch cohort of patients with N -methyl-d-aspartate receptor (NMDAR) encephalitis, 80%presented with psychiatric symptoms while 62% were initially referred to a psychiatric service.• Apart from testing for anti-NMDAR antibodies in serum and/or cerebrospinal fluid (CSF) the most sensitive ancillary investigations were electroencephalography (EEG) (abnormal in 100% of tested patients), CSF routine examination (abnormal in 93%) and magnetic resonance imaging (MRI) (abnormal in 40%).• This study supports the idea that early recognition and treatment of NMDAR encephalitis results in better outcome.• Symptomatic antipsychotic therapy was generally ineffective on its own and required many drug switches until the inflammatory process was treated.

An Atypical Case of Anti-NMDA Receptor Encephalitis: Predominant Parkinsonism and Persisting Micrographia without Oro-facial Dyskinesia

“…We should investigate the presence of anti-NMDAR antibodies in patients with acute or subacute encephalitis of unknown etiology, even if the clinical course is atypical, as reported previously (6). We considered basal ganglia lesions as the probable cause of parkinsonism in our case, and the severity of parkinsonism seemed to correlate with the degree of abnormal radiological findings in the basal ganglia.…”

The Psychiatric Phenotype of Anti-NMDA Receptor Encephalitis

“…3 Indeed, prominent psychiatric symptoms in anti-NMDAR encephalitis result in up to 60% of patients being initially admitted to psychiatric units. 4 This can delay diagnosis and appropriate treatment significantly. While there is hope that with increasing recognition of the disease this number is decreasing, it remains an important differential for patients under psychiatric care.…”

Psychiatric Manifestation of Anti-NMDA Receptor Autoimmune Encephalitis

“…In 2013, Maat et al [7] reported samples from 15 patients (13 female, 2 male, mean age 24 years, range 5-56 years) who tested anti-NMDA receptor antibody posi- tive. Twelve of the 15 patients (80%) presented with prominent psychiatric symptoms and 8 were initially referred to a psychiatric service.…”