Miller Fisher and Pharyngeal–cervical–brachial Variants of Guillain–Barré Syndrome following Jellyfish Sting

Dear Editor, Guillain–Barré syndrome (GBS) is an acute immune-mediated polyradiculoneuropathy that causes sensory, motor, and autonomic dysfunction. It is often triggered by infections, trauma, or vaccinations, with Campylobacter jejuni, influenza, COVID-19, and Zika virus as common causes.[1,2] GBS includes variants such as acute inflammatory demyelinating polyneuropathy, the most common form, and Miller Fisher syndrome (MFS), characterized by ataxia, ophthalmoparesis, and areflexia, comprising 5%–10% of cases.[3] The rare PCB variant affects oropharyngeal, cervical, and brachial muscles, causing significant weakness and accounting for 2%–3% of GBS cases.[4] MFS and PCB share pathophysiology, with autoantibodies such as anti-TT01a and anti-GQ1b targeting neuronal gangliosides and driving symptoms.[5] Cases featuring an overlap between MFS and PCB have been documented, as well as associations with Bickerstaff brainstem encephalitis (BBE), suggesting a spectrum of overlapping immune-mediated neuropathies.[2,5] This report presents a unique case of GBS with overlapping MFS and PCB variants following a jellyfish sting, highlighting a rare and previously unrecognized potential trigger for GBS. A 68-year-old male with a history of coronary artery disease and hypertension developed slurred speech, loss of balance, and blurred vision 3 weeks after experiencing jellyfish venom exposure during a trip to San Francisco, located on the Pacific Ocean. On the day of the sting, he experienced an immediate allergic reaction, presenting with redness and itching at the contact site [Figure 1]. He was evaluated in the emergency department where he was informed about the potential toxicity of jellyfish venom and received symptomatic treatment for allergic manifestations. He was discharged the same day without any neurologic symptoms because his symptoms were effectively managed.Figure 1: Skin lesions observed on the patient’s arm and shoulder following jellyfish contactThe patient’s neurologic symptoms gradually worsened, peaking by week 3. On the 3rd day after symptom onset, he sought medical attention due to worsening symptoms. An examination showed normal mental status, bilateral facial weakness, nasal speech, ophthalmoplegia, and upper limb weakness; his lower limb strength was preserved. The patient had neck and bilateral upper limb weakness (MRC: 3/5 in deltoids and biceps, 5/5 in hand muscles) with limb hyporeflexia. A sensory examination revealed sensory loss in the hands and feet. His plantar reflexes were flexor, and his gait was ataxic. Neurophysiologic findings related to the symptoms were obtained on the 3rd and 6th days, showing axonal injury characterized by conduction loss or low amplitudes in sensory nerve studies, with a sural sparing pattern. H-reflex and blink reflex responses could not be obtained [Figure 2]. On day 21, some sensory conductions were absent, but sural sparing persisted, with no significant motor conduction changes. At 6 months, sensory conduction partially recovered. Needle electromyography showed no denervation, and motor conduction remained intact. Table 1 presents nerve conduction studies for days 3, 6, and 21.Figure 2: Loss of H-reflex studyTable 1: Nerve conduction studies (sensory conduction loss and sural sparing observed on days 3, 6, and 21)A lumbar puncture on day 3 revealed elevated protein (887 mg/dL; normal: 150–400 mg/dL), normal glucose (71 mg/dL; normal: 40–70 mg/dL), and no detected cells (white blood cells: 0–5/mm3). Cerebrospinal fluid antibody tests for anti-GM1 to sulfatide immunoglobulin G (IgG) were all negative. However, serum anti-GQ1b IgG was not tested, limiting the immunologic assessment. The patient was diagnosed as having overlapping MFS and PCB variants of GBS. After five sessions of plasmapheresis with no significant improvement, intravenous immunoglobulin (IVIG) (0.4 g/kg/day for 5 days) was initiated. Post-IVIG, his bulbar symptoms improved, neck and facial muscle strength returned, and ataxia and eye movement restrictions partially resolved. The patient was then transferred to rehabilitation for further recovery. A few cases of GBS after jellyfish contact have been reported. Devere described a similar case of acute flaccid paralysis, confirmed by clinical and electrophysiologic findings.[6] Another report by Pang and Schwartz highlighted the role of jellyfish venom in inducing immune-mediated peripheral neuropathy.[7] These cases suggest that jellyfish venom may act as an immunologic trigger, potentially through a molecular mimicry mechanism or direct toxin-mediated nerve injury.[6,7] Jellyfish belonging to the phylum Cnidaria have stinging nematocysts that inject venom into the skin, which can enter the bloodstream. Composed of polypeptides and enzymes, this venom may cause direct toxicity or trigger an autoimmune response.[8] In 1986, Ropper et al. reported that PCB caused rapid weakness in the oropharyngeal and shoulder muscles, sparing the lower limbs. It accounts for ~3% of GBS cases, mainly in males.[9] As described by Charles Miller Fisher in 1956, MFS presents with ophthalmoplegia, ataxia, and areflexia. Unlike classic GBS, it may follow a descending weakness pattern.[10] Both PCB and MFS are associated with specific ganglioside antibodies, particularly anti-TT01a and anti-GQ1b.[11,12] These autoantibodies disrupt peripheral nerve function, causing variant-specific symptoms. Their structural similarity may explain the PCB and MFS overlap in some cases.[13] Incomplete PCB cases may present as isolated oropharyngeal weakness; isolated bulbar palsy following C. jejuni infection further highlights the MFS-PCB spectrum.[14] PCB typically shows axonal involvement over demyelination; as in our case, sensory nerve action potential loss indicated axonal degeneration.[15] Differentiating MFS-PCB overlap from neuromuscular junction diseases and brainstem lesions is challenging. Repetitive nerve stimulation (RNS) showed no significant decremental or incremental responses, and the patient tested negative for acetylcholine and muscle-specific kinase antibodies, ruling out myasthenia gravis and botulism [Figure 3: RNS]. The absence of diurnal variation or botulinum toxin exposure further supported this. Normal cranial magnetic resonance imaging excluded brainstem ischemia, and electroencephalography ruled out BBE. Advanced imaging and electrophysiologic studies are crucial for accurate diagnosis. Despite their distinct features, GBS variants share a common treatment approach, with plasmapheresis and IVIG as standard therapies to improve outcomes.Figure 3: Repetitive nerve stimulation study at 2, 3, 5, and 50 Hz with recording from the abductor digiti minimi muscle. RNS: Repetitive nerve stimulationOur case underscores the need for awareness of the rare link between jellyfish envenomation and GBS variants, including the coexistence of PCB and MFS. Although the exact pathophysiology remains unclear, such cases highlight the importance of considering jellyfish venom exposure and other rare potential triggers in acute neurologic syndromes. Author contribution N.T. conceived and designed the study. N.T. and O.F.T. performed data collection and drafted the manuscript. G.V. conducted the literature review and contributed to data analysis and interpretation. H.B. supervised the research process and provided critical revisions to the manuscript. All authors reviewed and approved the final manuscript. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.