Title : Cognitive crossroads: Navigating autoimmune limbic encephalitis amidst neuropsychiatric complexity
Abstract:
Autoimmune limbic encephalitis (AILE) is a rare form of encephalitis that manifests with atypical neuropsychiatric symptoms. Anti-NMDA receptor, anti-LGI1, and anti-GAD65 antibodies are associated with abnormal inflammation of the limbic system, leading to focal neurological deficits, altered mental status, fevers, seizures, and mood disturbances not explained by another disorder. Diagnosing AILE requires a comprehensive evaluation to rule out common organic causes, which can be challenging due to the difficulty in distinguishing between infectious and autoimmune etiologies, often prolonging diagnosis and treatment. Imaging studies and electroencephalograms (EEGs) may reveal temporal lobe abnormalities, and results are often nonspecific. Testing typically involves identifying elevated auto-antibody titers in CSF and blood, though results can be inconclusive. Treatment includes primary immunosuppressive interventions such as intravenous immunoglobulin (IVIG) and corticosteroids, with potential escalation to long-term agents like cyclophosphamide and rituximab. Swift recognition and appropriate treatment are critical to optimize therapeutic outcomes, minimize neurological sequelae, and identify potential comorbidities.
We present a case of a 44-year-old female admitted for refractory seizures secondary to autoimmune limbic encephalitis (AILE). Since her initial diagnosis of AILE in 2016, which was delayed for many years due to inadequate diagnostic testing, she experienced recurrent breakthrough seizures and unexplained mood symptoms. Following a COVID-19 infection in 2021, her symptoms worsened and required nine infusions of IVIG, with clinical improvement. During the current admission, the patient exhibited new neuropsychiatric manifestations, including labile mood, facial dystonia, and pain upon tactile stimulation. EEG revealed moderate encephalopathy with frequent bitemporal epileptiform discharges but no distinct electrographic seizures. Magnetic resonance imaging of the head indicated moderate cerebral atrophy with ventricular dilation and gliosis in the right frontal lobe, consistent with prior infarct or trauma. An infectious and metabolic workup was negative for alternative causes. She was resumed on her usual extensive medical regimen consisting of five antiepileptic agents, an antipsychotic, and as-needed benzodiazepines. Adjustments to these medications were ineffective in controlling the symptoms; therefore, IVIG treatment was re-initiated. Throughout her course, she experienced numerous musculoskeletal contractures, resulting in significant pain throughout her body, and multiple rapid responses were called for these concerns. Additionally, she failed multiple attempts at swallowing, necessitating nutrition via a nasojejunal tube, and she eventually received a percutaneous endoscopic gastrostomy (PEG) tube placement. The patient is improving minimally and will be transferred to a long-term care facility for further management and care.
Emerging studies have identified a link between COVID-19 and an increased prevalence of autoimmune encephalitis, potentially caused by mechanisms such as molecular mimicry, cytokine storms, direct viral invasion, and autoantibody production. Currently, the precise cause of this presentation remains unclear, highlighting the necessity for further research to differentiate it from other neurological, infectious, or psychiatric conditions. This case illustrates the complexities in diagnosing and managing AILE, especially in patients with preexisting medical conditions. Despite multiple IVIG courses, persistent seizures and neuropsychiatric manifestations underscore therapeutic challenges. Timely recognition, aggressive treatment, and continuous monitoring are crucial for managing AILE to minimize neurological sequelae and improve overall quality of life.
