Recurrent Panic Attack and Bilateral Hippocampus Lesions as Main Manifestation in an Autoimmune Encephalitis Associated with Primary Biliary Cirrhosis
Autoimmune encephalitis (AE) is a group of central nervous system (CNS) inflammatory diseases mediated by autoantibodies, characterized by a wide spectrum of neuropsychiatric symptoms. Common manifestations include cognitive impairment, epileptic seizures, and mental behavior disorders, often accompanied by lesions in both limbic and extra-limbic brain structures visible on radiologic imaging. While AE has been increasingly recognized in recent years and is often associated with multiple autoimmune diseases, there is limited literature on its co-existence with primary biliary cirrhosis (PBC). This case report presents a rare instance of AE in a patient with PBC, highlighting the clinical presentation, diagnostic challenges, and therapeutic outcomes.
The patient, a 27-year-old woman, was admitted to the hospital in February 2019 with a one-month history of memory deterioration and recurrent panic attacks. One month prior to her admission, she had gradually developed short-term memory loss and experienced sudden, transient episodes of panic. These episodes were accompanied by nausea, dizziness, chest congestion, and limb tremors. Initially, she sought treatment at a local hospital, where she was assessed using the Hamilton Depression (HAMD) and Anxiety (HAMA) scales and diagnosed with moderate depression and significant anxiety. Seeking further evaluation and treatment, she was referred to our hospital.
The patient’s medical history revealed a diagnosis of autoimmune hepatopathy (AIHT) in May 2018 during her mid-trimester pregnancy. At that time, she was treated with ursodeoxycholic acid (250 mg, once daily) for one month. She later gave birth to a healthy baby boy via natural labor in September 2018. Her personal and family history was otherwise unremarkable. Upon neurological examination, significant impairment in short-term memory was noted, while other cognitive functions appeared normal.
Laboratory tests revealed moderately elevated levels of alanine aminotransferase (ALT) at 75 U/L (normal range: 7–10 U/L), aspartate aminotransferase (AST) at 54 U/L (normal range: 13–35 U/L), and markedly increased alkaline phosphatase (ALP) at 295 U/L (normal range: 35–100 U/L) and gamma-glutamyltransferase (GGT) at 677 U/L (normal range: 7–45 U/L). Blood ammonia levels were within the normal range at 19 mmol/L (normal range: 18–72 mmol/L). Serum autoantibody analysis detected strongly positive anti-mitochondrial antibody M2 (AMAM2) and positive anti-nuclear antibody (ANA). Anti-neutrophil cytoplasmic antibodies (ANCA), including pANCA and cANCA, were within normal limits. Additional blood and urine tests for amino acid and acyl carnitine spectra were unremarkable. Cerebrospinal fluid (CSF) analysis showed no evidence of bacterial, fungal, or viral infections, and no autoantibodies were detected.
Electroencephalogram (EEG) recordings, both short-term and long-term, did not reveal epileptic waves. However, T2-weighted and flair magnetic resonance imaging (MRI) demonstrated symmetric swelling changes and high-intensity signals in the bilateral hippocampus regions. Based on the laboratory findings, a diagnosis of PBC was confirmed, and treatment with ursodeoxycholic acid (500 mg, twice daily) was initiated, leading to improvement in liver function. Despite anti-anxiety and antidepressant therapy with paroxetine (20 mg, once daily), estazolam (0.5 mg, three times daily), and olanzapine (2.5 mg, once daily), the patient’s symptoms persisted.
Given the clinical presentation and imaging findings consistent with AE, and after ruling out other possible CNS diseases, a diagnosis of AE was established. The patient was treated with intravenous immunoglobulin (0.4 g/kg, once daily for five days), followed by oral methylprednisolone (44 mg, once daily, with a gradual taper of 8 mg every two weeks). This treatment regimen resulted in significant alleviation of her panic attacks. At a three-month follow-up, the patient reported resolution of both panic attacks and memory loss. However, she declined further testing for AMAM2 levels or repeat MRI due to personal reasons.
This case represents a rare instance of AE associated with PBC. The patient exhibited atypical clinical symptoms for hepatopathy, presenting primarily with mental behavior disorders, short-term memory loss, and panic attacks, alongside bilateral hippocampus lesions and the presence of AMAM2. While no previously established AE-associated antibodies were detected in the CSF, the strong positivity of AMAM2 in the serum raises questions about its potential role in CNS involvement. Previous studies have reported AMAM2 in patients with systemic lupus erythematosus (SLE) and CNS involvement, suggesting a possible link between AMAM2 and CNS diseases. However, the exact role of AMAM2 in AE remains unclear, and further research is needed to determine whether it is a novel AE-related autoantibody or a marker for other CNS-involved diseases.
The co-occurrence of AE and PBC in this patient suggests a potential overlap between the two conditions. Previous case reports have described PBC patients with limbic encephalitis and bilateral hippocampal involvement, with immunosuppressive therapy leading to symptom resolution and imaging improvements. While the existence of a PBC/AE overlap syndrome remains unproven, the coexistence of these two autoimmune conditions in the same patient suggests a possible relationship between them.
In conclusion, this case report highlights a novel clinical entity of AE associated with PBC, characterized by the presence of AMAM2 and symmetric high-intensity lesions in the bilateral hippocampus, manifesting as short-term memory loss and panic attacks. Whether this represents a true PBC/AE overlap syndrome or whether AMAM2 plays a direct role in AE requires further investigation. Future research should focus on elucidating the mechanisms underlying this association and exploring potential therapeutic targets.
doi.org/10.1097/CM9.0000000000000611
Was this helpful?
0 / 0