Neuropathy patients have variable sensory disturbance (loss or exaggerated sensation including with pain), weakness, and autonomic involvements (sweat abnormalities, gastrointestinal dysfunction, and lightheadedness on standing). These symptoms are a result of injury to the distal nerves, roots, and ganglia or their gathering points (nerve plexus in the thighs and arms). Patients may have symmetric or asymmetric involvement of the extremities, trunk, and head, including extraocular muscles. Subacute onsets and asymmetric involvements favor inflammatory or immune causes over inherited or metabolic forms. Depending on the specific inflammatory or immune-mediated causes, other parts of the nervous system may also be affected (brain, cerebellum, spinal cord). Nerve conduction studies and needle electromyography can help classify the neuropathy as primary axonal, primary demyelinating, or mixed axonal and demyelinating.
Among the immune-mediated peripheral neuropathies, autoantibodies to gangliosides represent an important class of noncancer-associated autoimmune peripheral neuropathies. Gangliosides are glycosphingolipids that contain sialic acid and are present in many cell types, most abundantly within neural tissues along their linings (myelin). Depending on the specific ganglioside autoantibody found and the antibody titer, in the appropriate clinical context these findings may be supportive of a specific clinical diagnosis and may also be prognostic for treatment response.(1,2)
Specifically, in multifocal motor neuropathy (MMN) and multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy, also known as Lewis-Sumner syndrome or multifocal chronic immune demyelinating polyradiculoneuropathy, the presence ganglioside autoantibodies, particularly high-titer GM1 IgM autoantibodies, may be supportive of the diagnosis in the correct clinical context. Furthermore, ganglioside seropositivity has been associated with favorable response to immunotherapy among patients suspected to have MMN during the initial clinical evaluation.(1)
Additionally, the presence of ganglioside antibodies may support a diagnosis of Guillain-Barre syndrome (GBS) in the appropriate clinical context.(3) GBS is a class of autoimmune peripheral neuropathies that comprises a spectrum of disorders, including acute inflammatory demyelinating polyradiculoneuropathy, acute motor axonal neuropathy, and acute motor and sensory axonal neuropathy. This class of autoimmune neuropathies is generally characterized by an acute onset. Although the diagnosis of these disorders is dependent on clinical evaluation and electrophysiologic studies, assessment of ganglioside antibodies can further support the diagnosis.