Case Report: A case of paraneoplastic autoimmune encephalitis with concurrent anti-GABABR and anti-SOX1 antibody positivity

Abstract

Background Paraneoplastic autoimmune encephalitis (PAE) is most commonly associated with small cell lung cancer (SCLC). Anti–γ-aminobutyric acid B receptor (GABABR) antibodies underlie a treatable limbic syndrome, whereas anti–SRY-box transcription factor 1 (SOX1) antibodies serve as high-specificity onconeural biomarkers of SCLC-driven autoimmunity. The sequential emergence of these two antibodies during the longitudinal course of a single patient has rarely been documented. Case presentation A 75-year-old man presented with episodic impaired consciousness, behavioural disturbance and rapid cognitive decline. Brain MRI showed bilateral hippocampal signal abnormalities. A cell-based assay (CBA) detected anti-GABABR antibodies at high titre in serum (1:3200) and cerebrospinal fluid (CSF; 1:1000), while a tissue-based assay (TBA) on rat brain confirmed a neuronal cell-surface staining pattern; the full paraneoplastic panel, including anti-SOX1, was negative, and initial tumour screening was unrevealing. A diagnosis of anti-GABABR encephalitis (initially regarded as non-paraneoplastic) was made and the patient improved with intravenous immunoglobulin (IVIG), high-dose corticosteroids and maintenance mycophenolate mofetil. During a refractory second relapse 5 months later, repeat CBA showed rising anti-GABABR titres (serum 1:10,000; CSF 1:1000) and newly positive anti-SOX1 antibodies (serum 1:100; CSF 1:1); a previously occult right superior mediastinal mass radiologically compatible with SCLC was identified on repeat chest CT. The diagnosis was revised to anti-GABABR/anti-SOX1 dual-antibody PAE (probable PNS by 2021 PNS-Care criteria). The family declined biopsy, PET/CT and antitumour therapy because of advanced age and frailty; repeated IVIG with continued immunosuppression achieved partial clinical stabilisation with persistent cognitive impairment. Conclusion Apparently isolated anti-GABABR encephalitis can evolve into dual anti-GABABR/anti-SOX1 paraneoplastic disease, with the second antibody heralding an occult SCLC. Repeating both CBA-based and intracellular antibody panels at every clinical relapse, together with repeat thoracic imaging, is essential to avoid missing an evolving paraneoplastic aetiology.