Guillain–Barré syndrome with unilateral oculomotor nerve palsy and anti-GM3 IgG antibodies

Abstract

Guillain–Barré syndrome (GBS) is a life-threatening acute paralytic neuropathy characterized by rapidly progressive limb weakness and bilateral cranial nerve involvement. We report an early 70s male with no relevant medical history diagnosed with anti-GM3 IgG-positive GBS, who developed unilateral oculomotor nerve palsy and autonomic dysfunction during intravenous immunoglobulin (IVIG) therapy, with spontaneous symptom resolution following IVIG completion. Six-month follow-up assessments confirmed complete remission. This case reinforces the therapeutic value of IVIG in GBS patients with specific autoantibody profiles, even when complicated by transient neurological deterioration during treatment.

Introduction

Guillain–Barré syndrome (GBS) is an immune-mediated polyradiculoneuropathy and the leading cause of acute flaccid paralysis worldwide, exhibiting marked clinical heterogeneity. Its classic presentation consists of symmetric ascending weakness (with or without cranial nerve involvement) and hyporeflexia. ¹ GBS subtypes are associated with specific antiganglioside antibodies; for instance, acute motor axonal neuropathy (AMAN) is linked to IgG antibodies against GM1 and GD1a, whereas Miller Fisher syndrome is characterized by anti-GQ1b reactivity. ^{2 , 3} In contrast, the target antigens in acute inflammatory demyelinating polyneuropathies (AIDP), the most common GBS subtype, are unidentified. Intravenous immunoglobulin (IVIG) and plasma exchange serve as first-line immunotherapeutic therapies that can accelerate recovery in GBS. ⁴ However, GBS remains a potentially disabling disease, with up to 20% of patients unable to walk independently one year after onset despite standard treatment. ¹ Herein, we report a unique case of anti-GM3 IgG-positive AIDP. The patient initially presented with unilateral ophthalmoplegia, which progressed to autonomic dysfunction during IVIG infusion. Notably, significant clinical improvement was observed following therapy completion.

Case report

An elderly male in his early 70s with no relevant medical history developed acute symmetric limb weakness and distal paresthesia one week after an influenza infection and was admitted to Yueyang Central Hospital in mid-2024. Neurological examination revealed symmetrical distal limb weakness (Medical Research Council (MRC) grade 3), ⁵ universal areflexia, and distal superficial sensory impairment. Diagnostic investigations revealed isolated positivity for anti-GM3 IgG antibodies, while neuroimaging (brain and spinal magnetic resonance imaging (MRI)) and serum/cerebrospinal fluid (CSF) virology profiles were normal. Nerve conduction studies demonstrated prolonged motor distal latencies, reduced motor conduction velocities, and absent F-waves, with preserved compound action potential amplitudes (Table 1). CSF analysis on illness day 3 showed albumin-cytologic dissociation (protein 1026.5 mg/L, leucocytes 5 × 10⁶/L). Both serum and CSF antiganglioside antibodies were examined using cell-based assays, which detected isolated anti-GM3 IgG antibody positivity. The patient was diagnosed with AIDP and immediately received IVIG at 400 mg/kg for five consecutive days. On the fourth day of IVIG, he developed persistent diplopia and worsening limb weakness (MRC grade 2 in all limbs), followed by urinary retention and abdominal distension. Repeated neurological examination showed complete right oculomotor nerve palsy. Comprehensive neurovascular imaging (contrast-enhanced brainstem MRI and magnetic resonance angiography) ruled out structural lesions. Repeat CSF analysis revealed progressive abnormalities, with elevated CSF protein (1525.5 mg/L) and mild pleocytosis (26 × 10⁶/L white blood cells). IVIG therapy was continued, and electrocardiographic monitoring was initiated to screen for autonomic arrhythmia. By day 7, adduction and vertical gaze limitations had dramatically improved, and ptosis had resolved completely. One month after admission, the patient was discharged with substantially improved limb strength (MRC grade 5 in upper limbs, grade 5- in lower limbs). At the six-month follow-up, he exhibited complete resolution of ophthalmoplegia with full ocular motility, unassisted ambulation, and normal gait. Repeated serological testing showed negative antiganglioside antibody titers, indicating absence of ongoing autoimmune activity (Figure 1). This study conforms to CARE guidelines. ⁶ Written informed consent for treatment and publication was obtained from the patient, and all identifying information has been removed.

Figure 1.

The clinical timeline of the patient. The clinical timeline documented the patient's disease course and corresponding time points.

Table 1.

Nerve conduction study of peripheral nerves.

Nerve	Amplitude (mV)	DML (ms)	NCV (s)	F-wave latency (ms)
R. tibial motor	15.3 (≥5)	7.7↓ (range ≤ 6）	48 (≥40)	NR
L. tibial motor	16 (≥5)	6 (range ≤ 6）	47 (≥40)	NR
R. median motor	7.8 (≥5)	4.1↓ (range ≤ 4）	48↓ (≥50)	NR
L. median motor	8.8 (≥5)	3.9 (range ≤ 4）	48↓ (≥50)	NR
R. median sensory	8.1 (≥5)	—	33↓ (≥55)	NR
L. median sensory	8.4 (≥5)	—	27↓ (≥55)	NR

DML: distal motor latency; NCV: nerve conduction velocity.

Nerve conduction studies revealed prolonged motor distal latencies, reduced motor conduction velocities, and absent F-waves, with preserved compound muscle action potential amplitudes, consistent with demyelinating polyneuropathy.

Discussion

AIDP, the most common subtype of GBS, typically presents as monophasic symmetrical limb weakness with universal areflexia. ⁷ Although ophthalmoplegia in GBS is classically associated with anti-GQ1b antibodies targeting gangliosides enriched in cranial nerves III, IV, and VI, we report the first case of AIDP featuring unilateral oculomotor palsy with exclusive anti-GM3 IgG antibody positivity.^8,9 GM3, a structurally simple monosialoganglioside composed of a terminal sialic acid residue, lactose moiety, and ceramide backbone, functions as a key modulator of cell growth and differentiation in the central nervous system. ¹⁰ Anti-GM3 IgG antibody was initially identified in children with AMAN and subsequently linked to facial nerve palsy and sensory impairment in a Chinese cohort.^11,12 It has also been associated with the pharyngeal–cervical–brachial variant of GBS, characterized by predominant bulbar palsy, ⁸ and rare cases of acute-onset chronic inflammatory demyelinating polyneuropathy presenting with rapidly progressive bilateral weakness and distal numbness responsive to IVIG. ¹³ Moreover, co-occurrence of anti-GM3 and anti-GM4 antibodies in glial fibrillary acidic protein astrocytopathy may mimic Brown–Sequard syndrome, ¹⁴ while anti-GM3 antibodies have also been implicated in atypical Miller Fisher syndrome ¹⁵ and virus-triggered neurological disorders, including herpes simplex encephalitis and H1N1 vaccination-associated narcolepsy–cataplexy.^16,17 In contrast to these established associations, our case exhibited a distinct clinical course: initial AIDP symptoms were followed by progression to unilateral oculomotor palsy and autonomic dysfunction during IVIG treatment, with subsequent remission after therapy completion.

This novel presentation may expand the clinical spectrum of anti-GM3 IgG antibodies, which previously included narcolepsy–cataplexy, facial neuropathy, Miller Fisher syndrome, and sensory ganglionopathy. IVIG, the first-line therapy for GBS, exerts its effects through neutralization of pathogenic antiganglioside antibodies via formation of dimeric immune complexes. ¹ Approximately 10% of patients experience treatment-related fluctuation (TRF), defined as clinical deterioration after initial improvement or stabilization, which typically responds to IVIG retreatment. ¹⁸ Similarly, our patient developed transient unilateral ophthalmoparesis and autonomic dysfunction during IVIG treatment. Given the prolonged half-life of IVIG and the absence of life-threatening cardiorespiratory involvement, we continued IVIG treatment, and subsequent clinical improvement confirmed both the therapeutic efficacy of IVIG and the accuracy of the AIDP diagnosis.

Conclusion

GBS exhibits marked clinical heterogeneity in clinical presentations, severity of cranial nerve deficits, degree of autonomic dysfunction, and disease progression. Lumbar puncture and electrophysiological studies are crucial for subtype identification. Although IVIG is a well-established, effective therapy, residual deficits may persist in some patients. This case may expand the clinical spectrum of anti-GM3 IgG antibody-associated neurological manifestations and reinforces the fundamental role of IVIG in GBS management. However, this special association warrants further investigation. Furthermore, the observed transient neurological deterioration during treatment underscores the importance of differentiation between disease progression and TRF in therapeutic decision-making, highlighting that timely and targeted intervention is essential for optimizing prognosis in GBS.