By Hai H. Hoang, MD
Lee SU, Kim HJ, Choi JY, et al. Expanding clinical spectrum of anti-GQ1b antibody syndrome: A review. JAMA Neurol 2024;81:762-770.
Antibodies targeting gangliosides, glycosphingolipids that play a role in synaptic plasticity, neurotransmission derangements, and axonal growth all are implicated in many autoimmune peripheral neuropathies. Miller Fisher syndrome (MFS) is the clinical triad of external ophthalmoplegia, ataxia, and areflexia classically associated with anti-GQ1b. However, there are other subtypes that present with only one or two clinical features of the clinical triad.
Typical anti-GQ1b antibody syndrome with ophthalmoplegia includes classic MFS but may overlap with Guillain-Barré syndrome, Bickerstaff brainstem encephalitis, and acute ophthalmoplegia without ataxia. The ophthalmoplegia associated with these syndromes includes, most commonly, bilateral abduction failure or total oculomotor paresis, and, to a lesser degree, iridoplegia or multiple asymmetrical ocular motor palsies.
Atypical anti-GQ1b syndrome without ophthalmoplegia includes acute vestibular syndrome, optic neuropathy with disc swelling, and acute sensory ataxic neuropathy. In patients with optic disc swelling who do not fit typical optic neuritis or papilledema, this anti-GQ1b syndrome should be considered.
Detection of the serum antibody within one or two days of the onset of neurologic deficits implies that the antibody indeed is involved in the pathogenesis and not an epiphenomenon caused by tissue destruction. Measurement of antibodies in the cerebrospinal fluid confer no further diagnostic benefit.
Anti-GQ1b antibody should be considered when developing a differential diagnosis for patients who may have been given a diagnosis of Wernicke encephalopathy, multiple sclerosis, neuro-Behçet disease, myasthenia gravis, pituitary apoplexy, and Tolosa-Hunt syndrome.
Intravenous immunoglobulin (IVIG) inhibits the binding of antibodies to GQ1b, thereby preventing complement activation. Clinical data suggest IVIG may hasten recovery of ophthalmoplegia and ataxia, while plasmapheresis does not. Unfortunately, observational clinical data are not supported by randomized clinical trials.
Recovery from neurological deficits may take between four and 12 weeks depending on severity. Relapses occur in 14% of cases, mostly in patients with underlying human immunodeficiency virus infections or cancers. Ganglioside antibodies are associated with certain cancers, including thyroid cancer.
Commentary
This clinical review expands the range of clinical disorders associated with anti-GQ1b and helps to provide more definitive diagnoses to patients in whom an autoimmune process is suspected. Although we commonly give IVIG to patients with these types of presentations, often we struggle when discussing prognosis or disease surveillance. Detection of anti-GQ1b antibody can provide clinicians and patients with information regarding long-term prognosis and guidance that often is not available in rare neurologic syndromes.
Hai H. Hoang, MD, is Assistant Professor of Clinical Neurology, Weill Cornell Medical College.
