The Diagnostic Challenge of Seronegative Autoimmune Encephalitis With Super-Refractory Status Epilepticus

Abstract

Autoimmune encephalitis is an immune-mediated syndrome, with sub-acute to chronic presentations, such as memory impairment, altered sensorium, behavioral abnormality, psychosis, and seizures. It poses a twofold diagnostic challenge: firstly, because of its variable clinical presentation and secondly, due to the wide variety of autoimmune antibodies causing it, which makes it difficult to identify the underlying etiology. Treatment should not be delayed due to pending laboratory workup, as early recognition and initiation of therapy prevents long term neurological sequelae. This is a case report of a 59-year-old female who presented with neuropsychiatric symptoms, which evolved into refractory status epilepticus and autonomic dysfunction, requiring anesthesia induced coma. While her MRI had positive findings of encephalitis, she tested negative for infectious diseases and antibody panels.

Diagnostic Challenges and Treatment Approach to Seronegative Autoimmune Encephalitis

“…Current guidelines to definitively diagnose autoimmune encephalitis require confirmation of autoantibody presence or absence obtained from paraneoplastic, NMDA receptor, and other autoantibody panels that often cause significant delays in diagnosis and treatment [ 2 , 3 ]. Early recognition and initiation of treatment of seronegative encephalitis has been associated with improved patient outcomes, decreased mortality, and fewer cases of disease relapse [ 9 , 11 , 12 ]. It is our recommendation for clinicians suspicious of seronegative AE to utilize the criteria for ANPRA proposed by Graus et al which state that ANPRA diagnosis can be confirmed when the following four criteria are all met: (1) a patient experiences rapid progression of memory deficits, AMS, or psychiatric symptoms within three months, (2) exclusion of well-defined syndromes of autoimmune encephalitis, (3) absence of defined autoantibodies in serum or CSF, and (4) reasonable exclusion of alternative causes [ 2 ].…”

“…Seronegative autoimmune encephalitis is a rare subtype of autoimmune encephalitis that occurs when there is no identifiable, pathologic autoantibody in either the cerebrospinal fluid (CSF) or serum of the patient. At present, the lack of identifiable autoantibodies in seronegative AE is hypothesized to be caused by unidentified autoantibodies that have not currently been discovered [ 8 , 9 ]. Ultimately, the lack of diagnostic testing to confirm seronegative AE results in diagnostic challenges and delayed treatment.…”

Movement disorders in cell surface antibody mediated autoimmune encephalitis: a meta-analysis

“…An important though problematic area in this field is the entity of seronegative AE, which may account for up to 50% of all AE (74). A 2016 consensus paper proposed a set of diagnostic guidelines that do not rely on antibody status, providing a basis for identification of seronegative cases (75).…”