Use and Safety of Immunotherapeutic Management of N-Methyl-d-Aspartate Receptor Antibody Encephalitis

Abstract

Key Points Question What are the most effective treatments for N -methyl- d -aspartate receptor (NMDAR) antibody encephalitis? Findings In this meta-analysis of individual patient data including 1550 cases, treatment factors at first event that were significantly associated with good functional outcome 12 months from disease onset included first-line treatment with therapeutic apheresis alone, corticosteroids in combination with intravenous immunoglobulin (IVIG), or corticosteroids in combination with IVIG and therapeutic apheresis, while lack of immunotherapy within 30 days of disease onset was significantly associated with poor outcome. Rituximab and long-term IVIG use were significantly associated with nonrelapsing disease course. Meaning Separate treatment factors are associated with functional outcomes and relapsing disease biology in those with NMDAR antibody encephalitis.

Current Status of Biomarkers in Anti-N-Methyl-D-Aspartate Receptor Encephalitis

“…The majority of patients initially present subacute psychiatric symptoms such as mania, social withdrawal, and psychosis. Subsequently, this initial clinical picture is rapidly followed by neurological abnormalities including short-term memory impairment, seizures, movement disorders, central hypoventilation, and even altered level of consciousness leading to intensive care unit (ICU) in up to 50% of adult patients [ 14 ]. Nonetheless, movement disorders and partial seizures are more frequently the first symptom in children [ 15 , 16 ], while male adults often have isolated focal seizures preceding the full clinical picture [ 17 ].…”

“…Supporting this hypothesis, Chefdeville et al found that ovarian teratomas associated with anti-NMDAR encephalitis contain nervous glial tissue, and among them, 82% express the GluN1 subunit of the NMDAR [ 20 ]. However, a recent meta-analysis showed that paraneoplastic cases account for only 25% of cases [ 14 ], suggesting that other unknown pathogenic mechanisms may lead to the immune tolerance breakdown in anti-NMDAR encephalitis. Likewise, a few viral infections have been reported as triggers of anti-NMDAR encephalitis, especially herpes simplex 1 virus (HSV1) encephalitis [ 13 , 21 , 22 ].…”

“…The most explored subset of outcome predictors in anti-NMDAR encephalitis are based on the initial clinical characterization of this entity in large cohorts. For instance, ages younger than 2 years or older than 65 years and the need of ICU admission have been associated with poor long-term outcomes [ 14 , 15 , 42 ]. Regarding the impact of current treatments, poor outcomes have also been associated with a lack of immunotherapy in the first month after onset, while early instauration of plasma exchange, steroids with intravenous immunoglobulins, or the combination of the three has been associated with good prognosis [ 14 ].…”

“…For instance, ages younger than 2 years or older than 65 years and the need of ICU admission have been associated with poor long-term outcomes [ 14 , 15 , 42 ]. Regarding the impact of current treatments, poor outcomes have also been associated with a lack of immunotherapy in the first month after onset, while early instauration of plasma exchange, steroids with intravenous immunoglobulins, or the combination of the three has been associated with good prognosis [ 14 ]. Interestingly, treatment delay longer than 1 month and ICU admission have been combined with other immunologic and clinical variables (CSF pleocytosis > 20 cells/mm 3 , abnormal magnetic resonance imaging (MRI), and lack of improvement after 1 month from treatment onset) to predict outcomes in a grading score termed the anti-NMDAR encephalitis one-year functional status (NEOS) score [ 12 ].…”

“…Interestingly, treatment delay longer than 1 month and ICU admission have been combined with other immunologic and clinical variables (CSF pleocytosis > 20 cells/mm 3 , abnormal magnetic resonance imaging (MRI), and lack of improvement after 1 month from treatment onset) to predict outcomes in a grading score termed the anti-NMDAR encephalitis one-year functional status (NEOS) score [ 12 ]. Indeed, the accuracy of this score has recently been validated in the aforementioned meta-analysis including 694 patients, although it was modified due to the frequent unavailability of the time to response from treatment onset [ 14 ].…”