GALOP syndrome: a treatable immune-mediated late-age onset polyneuropathy with gait ataxia.

Various studies have established an association between elevated titers of antibodies against sulfatide (the main acidic glycosphingolipid component of the myelin sheath) and a number of systemic and neurologic disorders. These auto-antibodies have been reported in patients with idiopathic thrombocytopenic purpura, (1) autoimmune chronic active hepatitis, (2) human immunodeficiency virus, (3) Guillain-Barre syndrome, (4) and chronic inflammatory demyelinating polyradiculoneuropathy. (5)

In the past decade, most researchers have focused on the association between these auto-antibodies and peripheral neuropathies. (6) Pestronk et al. (7,8) identified a subgroup of older patients with peripheral neuropathy, gait ataxia, and elevated titers of serum immunoglobulin M (IgM) binding to galopin and used the term GALOP syndrome (Gait disorder, Antibody, Late-age Onset, Polyneuropathy) to delineate common features among these patients. The authors also reported experience with three different treatment modalities in the management of their six patients with GALOP syndrome: 1) plasma exchange, 2) intravenous immunoglobulin (IV Ig), and 3) cyclophosphamide. (6) However, our knowledge of GALOP syndrome remains limited to anecdotal reports. Significant details of this syndrome remain unknown, such as the relationship between IgM auto-antibodies, central nervous system myelin antigens, and clinical features of GALOP syndrome, particularly ataxic gait. In addition, the frequency of occurrence of these auto-antibodies in patients with chronic polyneuropathies is unclear.

In this issue of the Southern Medical Journal, Alpert (9) reports the first case of GALOP syndrome with a 7-year follow-up. This case involves an elderly female patient who initially presented with gait ataxia associated with sensory complaints, weakness of the distal lower extremities, and diffuse hyporeflexia. Electrophysiologic examination showed abnormalities supporting a diagnosis of sensory motor polyneuropathy with primary axonal loss. Serum immunofixation showed a monoclonal IgM kappa protein, and GALOP autoantibody screen revealed very high titers of specific IgM binding to the GALOP antigen. Neuropathologic examination of the sural nerve disclosed a loss of myelinated nerve fibers with segmental demyelination of teased nerve fibers and mild axonal loss. Periodic treatment with IV Ig increased the strength of her distal lower extremities and improved her gait ataxia. Discontinuation of IV Ig therapy was followed by a recurrence of the clinical manifestations of GALOP syndrome as well as a rise in GALOP auto-antibody titers. A thorough seven-year follow-up of this patient has indicated that longterm immunosuppressive therapy is a crucial step in the stabilization of these patients.

Current knowledge is limited concerning the treatment and long-term prognosis of patients with peripheral neuropathies associated with antisulfatide antibodies and GALOP syndrome. Alpert's is the first report which highlights the long-term follow-up of a patient with GALOP syndrome, and which demonstrates the role of IV Ig in the management of this relatively unknown syndrome. The patient's favorable therapeutic response to IV Ig, which was associated with a drop in antisulfatide antibody titers, further emphasizes the role of the immune system in the pathogenesis of GALOP syndrome and the significance of chronic immunosuppression in management of these patients.

In conclusion, a diagnosis of GALOP syndrome should be strongly considered in elderly patients with peripheral neuropathy and otherwise idiopathic gait dysfunction, since it may be treatable with IV Ig.

Accepted November 16, 2003.

Copyright [c] 2004 by The Southern Medical Association

0038-4348/04/9704-0333

Please see "GALOP Syndrome: Case Report with 7-year Follow-up" on page 410 of this issue.

References

1. Van Villet HH, Kappers-Klune MC, van der Hel JW, Abels J. Antibodies against glycosphingolipids in sera of patients with idiopathic thrombocytopenic purpura. Br J Haematol 1987;67:103-108.

2. Toda G, Ikeda Y, Kashiwagi M, Iwamori M, Oka H. Hepatocyte plasma membrane glycosphingolipid reactive with sera from patients with autoimmune chronic active hepatitis; its identification as sulfatide. Hepatology 1990;12:664-670.

3. Petratos S, Turnbull VJ, Papadopoulos R, Ayers M, Gonzales MF. High titer anti-sulfatide antibodies in HIV-infected individuals. NeuroReport 1999;10:2557-2562.

4. Van den Berg LH, Lankamp CL, de Jager AE, et al. Anti-sulphatide antibodies in peripheral neuropathy. J Neurol Neurosurg Psychiatry 1993;56:1164-1168.

5. Pestronk A, Li F, Griffin J, et al. Polyneuropathy syndromes associated with serum antibodies to sulfatide and myelin-associated glycoprotein. Neurology 1991;41:357-362.

6. Latov N. Pathogenesis and therapy of neuropathies associated with monoclonal gammopathies. Ann Neurol 1995;37:S32-S42.

7. Pestronk A, Choksi R, Bieser K, et al. GALOP syndrome: a treatable autoimmune gait disorder with late-age onset. Ann Neurol 1993;34:268-269.

8. Pestronk A, Choksi R, Bieser K, et al. Treatable gait disorder and polyneuropathy associated with high titer serum IgM binding to antigens that copurify with myelin-associated glycoprotein. Muscle Nerve 1994;17:1293-1300.

9. Alpert JN. GALOP syndrome: case report with a 7-year follow-up. South Med J 2004;97;410-412.

Alireza Minagar, MD

From the Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, LA.

Reprint requests to Alireza Minagar, MD, Department of Neurology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130. Email: [e-mail]