INTRODUCTION: We present a rare case of acute immune-mediated polyradiculoneuritis, a Guillain-Barré Syndrome (GBS) variant, manifesting as ophthalmoparesis-ataxia, facial diplegia, and acute bulbar palsy, accompanied by a unique autoimmune profile. CLINICAL CASE: A 75-year-old female developed rapidly progressive symptoms, including bilateral non-reactive mydriasis, ptosis, complete ophthalmoplegia, bilateral facial weakness, tongue immobility, palatal paralysis, limb dysmetria, ataxia, and brisk generalized tendon reflexes, all while maintaining a preserved mental state. Symptoms emerged 10 days after a probable gastrointestinal infection. Severe bulbar dysfunction necessitated orotracheal intubation and a tracheotomy. Extensive cranial nerve involvement initially suggested a brainstem lesion, with oculomotor and acute bulbar palsy as prominent signs. However, brainstem and spinal magnetic resonance imaging along with cerebrospinal fluid analysis yielded negative results. Electromyography reveled a sensorimotor demyelinating polyradiculoneuropathy, and serum testing identified IgG antibodies targeting multiple gangliosides, including the disialosyl group and terminal NeuNAc(α2-3)Gal. Treatment with intravenous immunoglobulin (IVIG) led to gradual clinical improvement. CONCLUSIONS: This case highlights a rare and severe GBS phenotype characterized by reactivity to multiple gangliosides. It highlights the role of shared ganglioside epitopes in antibody-mediated neurological damage and expands the clinical spectrum of GBS variants.