Anti-NMDA receptor encephalitis in older adults: A systematic review of case reports.

OBJECTIVE: To ascertain the clinical characteristics of anti-NMDA receptor encephalitis (NMDARE) in older patients. METHOD: A systematic literature review using PubMed and Scopus of all published case reports of NMDARE was undertaken, from database inception to June 2020. From this, cases reporting on patients older than 65 years of age and whose diagnosis was confirmed by the presence of anti-NMDAR antibodies in CSF were selected. RESULTS: 23 case reports fulfilling the study's criteria were found. Median age was 70.1 years (range 65-84), fourteen were female (60.9%), and mostly presented with acute behavioral and cognitive changes (95.7%). Atypical psychosis occurred in eleven patients (47.8%) with a sudden onset and fluctuating clinical pattern of delusions (39.1%), hallucinations (30.4%), and motility disturbances (34.8%) including catatonia (17.4%). Nine patients presented with seizures (39.1%). Pleocytosis in CSF (>5 WBC) was described in twelve cases (52.2%). Eleven cases (47.8%) had abnormal brain magnetic resonance imaging (MRI) scans with limbic inflammatory lesions. Thirteen patients had an abnormal EEG (56.5%). CONCLUSION: NMDARE should be included in the differential diagnosis of older patients who present with new psychiatric episodes, especially when characterized by sudden onset psychotic polymorphic symptomatology, fluctuating course with marked cognitive decline, and with catatonic features.

Clinical, Neuroimmunologic, and CSF Investigations in First Episode Psychosis.

OBJECTIVES: To report the neuropsychiatric features and frequency of NMDA receptor (NMDAR) and other neuronal immunoglobulin G antibodies in patients with first episode psychosis (FEP) and to assess the performance of reported warning signs and criteria for autoimmune psychosis (AP). METHODS: This was a prospective observational study of patients with FEP assessed for neuropsychiatric symptoms, serum and CSF neuronal antibodies (brain immunohistochemistry, cell-based assays, live neurons), and warning signs and criteria of AP. Previous autoimmune FEP series were reviewed. RESULTS: One hundred five patients were included; their median age was 30 (range 14-75) years, and 44 (42%) were female. None had neuronal antibodies. Two of 105 (2%) had CSF pleocytosis, 4 of 100 (4%) had brain MRI abnormalities, and 3 of 73 (4%) EEG alterations. Thirty-four (32%) and 39 (37%) patients fulfilled 2 sets of warning signs of AP, and 21 (20%) fulfilled criteria of possible or probable AP, yet none developed AP. The cause of FEP was psychiatric in 101 (96%) and nonpsychiatric in 4 (4%). During this study, 3 patients with psychosis caused by anti-NMDAR encephalitis were transferred to our center; 2 did not meet criteria for possible AP. Of 1,159 reported patients with FEP, only 7 (1%) had CSF studies; 36 (3%) had serum NMDAR antibodies (without definite diagnosis of AP), and 4 had CSF NMDAR antibodies (3 classic anti-NMDAR encephalitis and 1 with isolated psychiatric features). CONCLUSIONS: NMDAR antibodies were not found in patients with FEP unless they had anti-NMDAR encephalitis. Warning signs and criteria for AP have limited utility when neurologic symptoms are absent or paraclinical tests are normal. A diagnostic algorithm for autoimmune FEP is provided.

Cycloid psychosis as a psychiatric expression of anti-NMDAR encephalitis. A systematic review of case reports accomplished with the authors' cooperation.

OBJECTIVE: We reviewed the psychotic symptoms of anti-NMDA receptor encephalitis (NMDARE) to differentiate its presentation from those found in a primary psychiatric disorder. We hypothesized that the cycloid psychosis (CP) phenotype would be a frequent clinical presentation in the psychiatric phase of NMDARE. METHOD: A systematic literature review in PubMed of all case reports published on NMDARE was performed from database inception to March 2020. We included all cases where psychotic symptoms were reported and whose diagnoses were confirmed by the presence of anti-NMDAR antibodies in the cerebrospinal fluid (CSF). An email including a short test (CP phenotype, Perris and Brockington's criteria) was sent to all case report authors asking them to describe the psychotic symptoms. RESULTS: We identified 335 case reports fulfilling our criteria, and the authors of 200 replied. Our analyses were based exclusively on those answers and data extracted from the articles. Median patient age was 25 years (+-11.4), 81% were female, and 39% had an ovarian teratoma. A complete CP phenotype was identified in 175 patients (87%). These were acute psychotic episodes with a sudden onset and a fluctuating clinical pattern mostly characterized by confusion (97%), delusions (75%), hallucinations (69%), motility disturbances (87%), and mood oscillations (80%). CONCLUSION: The complete CP phenotype was frequently the expression of psychotic symptoms in NMDARE. We suggest that patients with a first psychotic episode who initially exhibit the CP phenotype should undergo CSF analysis to determine whether antibodies against neuronal cell surface or synaptic receptors are present to rule out a possible diagnosis of autoimmune encephalitis.

Considerations of psychotic symptomatology in anti-NMDA encephalitis: Similarity to cycloid psychosis.

Most patients with anti-NMDA receptor (NMDAR) encephalitis present with acute psychosis which is difficult to differentiate from psychotic episodes related to a primarily psychiatric disease. A precise description of the psychiatric phenotype of this disease would greatly facilitate the early diagnosis of these patients. We provide here a detailed description of three of these patients and the similarity of the clinical features with cycloid psychosis. All three patients met Perris and Brockington's criteria for cycloid psychosis in the initial phase of the autoimmune process, including among other an acute and polysymptomatic onset, polymorphous psychotic symptomatology, mood swings, and changes in psychomotricity. In addition, none of the patients had experienced an extended psychiatric prodromal phase. External stress factors preceded symptom onset in the three patients, who also showed common base personality traits and intolerance to a range of antipsychotic treatments. Complementary studies disclosed that the three patients had ovarian teratoma as well as abnormal EEG, and CSF antibodies against NMDAR. Patients with anti-NMDAR encephalitis may present with clinical features that resemble cycloid psychosis. In addition, our patients did not have prodromal history of psychiatric symptoms and showed intolerance to antipsychotic medication, which all should raise concern for anti-NMDAR encephalitis, prompting CSF antibody testing.

El déficit cognitivo en lupus eritematoso: a propósito de un caso / Cognitive impairment in lupus erythematosus: a case report

RESUMEN El lupus eritematoso es una enfermedad autoinmune sistémica de etiología desconocida, que afecta principalmente a mujeres entre 20 y 50 años de edad, puede manifestarse de diversas maneras clínicas. El déficit cognitivo es uno de los síndromes neuropsiquiátricos más prevalentes en dicha enfermedad, pero no se ha descrito un perfil específico del deterioro. Existen dificultades en el proceso de detección del déficit cognitivo, debido a la propia variabilidad de la clínica y a las limitaciones de los instrumentos de valoración existentes. Se recomienda el uso de pruebas de neuroimagen y la exploración neuropsicológica como formas de evaluación. La evolución y el tratamiento, tanto farmacológico como la rehabilitación cognitiva, están influidos por la etiología del deterioro. Paciente mujer de 54 años diagnosticada de lupus eritematoso, se deriva para estudio neuropsicológico por problemas de concentración y de memoria reciente, presentó alteración en pruebas de neuroimagen, pero no se presentó repercusión en la autonomía personal. Las pruebas de cribado de déficit cognitivo presentan una controvertida fiabilidad para personas con lupus eritematoso. Es necesario realizar una exploración neuropsicológica exhaustiva que incluya la valoración del rendimiento cognitivo y de la funcionalidad. Los déficits (cognitivos) son variados y el curso y el tratamiento dependerán de la etiología del déficit (primario vs. secundario).

SUMMARY Lupus erythematosus is a systemic autoimmune disease with unknown etiology that mainly affects women aged 20-50 years and it can have very different clinical manifestations. Cognitive deficit is one of the most prevalent neuropsychiatric syndromes in lupus erythematosus, but a specific profile was never described for it. There are difficulties in the assessment process due to the variability of clinical symptoms and tools limitations. Neuroi-maging and neuropsychological examination are recommended to assess cognitive impairment. The evolution and treatment (pharmacological and cognitive rehabilitation) are influenced by etiology. Case: Woman (54 years) diagnosed with lupus erythematosus who was sent to a neuropsychological study due to her concentration and short-term memory problems. She showed alteration in neuroimaging studies, but she maintains personal autonomy. Conclusion: screening tests of cognitive impairment present reliability controversial for people with lupus erythematosus. An extensive neuropsychological assessment is necessary, including cognitive performance and functionality. Cognitive Impairment are varied, and the course and treatment depend on the etiology (primary vs. secondary).