Lower motor neuron syndromes defined by patterns of weakness, nerve conduction abnormalities, and high titers of antiglycolipid antibodies

Abstract

We studied 74 patients with progressive, asymmetrical lower motor neuron syndromes. Clinical features of these patients, including age, sex, disease duration, patterns of weakness, and reflex changes, were evaluated by review of records. In each patient the clinical features were compared to the type of nerve conduction abnormalities and to the specificities of high-titer serum antiglycolipid antibodies. Antibody specificities were determined by an enzyme-linked immunosorbent assay using purified glycolipids and carbohydrates as substrates. Our results show that high titers of antibodies to glycolipids are common in sera of patients with lower motor neuron syndromes. Selective patterns of reactivity indicate that specific carbohydrate epitopes on the glycolipids are the targets of the high-titer antibodies in individual patients with lower motor neuron syndromes. Several distinct lower motor neuron syndromes can be identified based on clinical, physiological, and antiglycolipid antibody characteristics. These syndromes include multifocal motor neuropathy with evidence of multifocal conduction block on motor, but not sensory, axons and frequent (84%) high titers of anti-GM1 ganglioside antibodies; a lower motor neuron syndrome with predominantly distal weakness early in the disease course, no conduction block, and a high incidence (64%) of anti-GM1 antibodies; and a lower motor neuron syndrome with predominant early weakness in proximal muscles and serum antibodies to asialo-GM1 that do not cross-react with GM1 ganglioside.

Application of Liposome Immune Lysis Assay for Studies on Anti-Ganglioside Antibodies.

“…In the serum from patients with certain neurological diseases, antibodies against GMl ganglioside (GM1), one of the most common gangliosides in the nervous system, are detected in high titers by the enzyme-linked immunosorbent assay (ELISA) [3][4][5][6][7]. The ELISA is commonly used for determination of anti-ganglioside antibodies with gangliosides fixed on surface of plastic wells, and the titers of anti-IgM or anti-IgG antibodies are assessed for the quantification of the antibodies.…”

Anti-Ganglioside Antibodies in Patients With Rheumatoid Arthritis Complicated by Peripheral Neuropathy

“…IgM anti-GMl antibodies are found in 60-80% of patients with multifocal motor neuropathy [23] and IgM anti-sulphatide antibodies have been described in chronic axonal sensory neuropathy [24], while IgG anti-GQlb antibodies are detected in patients with Miller Fisher syndrome [25]. In the present study, seven of the 12 patients (58%) with anti-ganglioside antibodies had antibodies to both gangliosides, with significant correlations between the IgM and IgG antibodies to both gangliosides.…”

Antiganglioside GM1 Antibodies and Their Complement Activating Capacity in Central and Peripheral Nervous System Disorders and in Controls

“…The variance in the literature in types and frequency of clinical syndromes associated with anti-GM1 antibodies [8,9,15,18,22,[48][49][50][51] may result in part from discrepancies in patient classification (e.g. the 1 patient who revealed the lowest IgM and IgG anti-GM1 levels in the MMN group in our study might have been classified dif-Uetz-von Allmen/Sturzenegger/Rieben/ Rihs/Frauenfelder/Nydegger ferently by another center) or from differences in the assay systems used [52]; the specificity of our assay depends on indications provided by the kit producer and we cannot exclude cross-reactivity with epitopes other than those associated with GM1.…”

“…The three immunoglobulin isotypes IgM, IgG, and IgA did participate to various extents in the anti-GM1 elevation [24]. The selective association of high titers of IgM anti-GM1 with chronic demyelinating motor neuropathies like MMN is now well established [15,17]. High titers of IgG anti-GM1 are found in individuals with axonal motor neuropathies, either acute such as the Chinese paralysis syndrome, or acute axonal motor neuropathy often associated with Campylobacter jejuni enteritis [11,25] or chronic asymmetric LMN [7].…”

“…Syndromes associated with high titers of antiganglioside GM1 (anti-GM1) antibodies are predominantly motor diseases that affect the lower motor neurons and their processes [15]. These can be acute motor axonal neuropathies, considered a special variant of GBS [7,11,16] or chronic asymmetric lower motor neuron syndromes (LMN) such as multifocal motor neuropathy (MMN) [15,[17][18][19][20][21], or chronic asymmetric lower motor neuron syndromes without conduction block [7,17].…”