Introduction. Clinical manifestations

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1 Polyneuropathy associated with antisulfatide antibodies By Louis H Weimer MD (Dr. Weimer of Columbia University received consulting fees from Roche.) Originally released May 15, 2000; last updated February 18, 2017; expires February 18, 2020 Introduction This article includes discussion of polyneuropathy associated with antisulfatide antibodies and sulfatide neuropathies. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations. Overview Antisulfatide neuropathy is an immune-mediated neuropathic disorder. It presents most commonly as an axonal sensory predominant polyneuropathy. However, demyelination may be seen in some cases. GALOP syndrome, a variant of antisulfatide neuropathy, is a disabling gait disorder in the elderly. Patients typically have gait ataxia and a distal sensory predominant polyneuropathy. This neuropathy is mostly demyelinating. Clinical testing for antisulfatide and anti-galop antibodies is useful in slowly progressive sensory or sensorimotor neuropathies affecting patients older than 50 years of age. Treatment for both involves neuropathic pain management and immunosuppression in the presence of demyelination. Historical note and terminology Antibodies against sulfatide, the major acidic glycosphingolipid in myelin, have been reported in a variety of systemic and neurologic disorders. These antibodies have been found in disorders such as idiopathic thrombocytopenic purpura (van Vliet et al 1987), autoimmune chronic active hepatitis (Toda et al 1990), HIV (Petratos et al 1999b; Lopate 2005), multiple sclerosis (Ryberg 1978), Guillain-Barré syndrome (Fredman et al 1991; Ilyas et al 1991; Van den Berg et al 1993), and chronic inflammatory demyelinating polyradiculoneuropathy (Pestronk et al 1991; Melendez-Vasquez et al 1997). Most studies have shown an association between highly elevated titers of antisulfatide antibodies and peripheral neuropathy (Nemni et al 1993; Latov 1995; Shigeta et al 1997; Ferrari et al 1998; Dabby et al 2000). In the first report describing antibodies to sulfatide in neuropathy, high titers were found in patients with chronic axonal, predominantly sensory neuropathy (Pestronk et al 1991). Other reports followed, but patients did not appear to constitute a single clinical syndrome, and some patients had demyelination, sometimes in association with antibodies against other myelin antigens (Ilyas et al 1992; Fredman et al 1993; Nobile-Orazio et al 1994). Pestronk and colleagues identified extremely high titers of IgM binding to a CNS myelin antigen that co-purified with myelin associated glycoprotein in patients with gait ataxia and sensorimotor polyneuropathy. This clinical syndrome was termed the GALOP syndrome (gait disorder, autoantibody to a neural antigen, late-age onset, and polyneuropathy of mild to moderate severity) (Pestronk et al 1994). The anti-cns myelin antigen antibody was also found to cross react with both sulfatide and myelin associated glycoprotein. Pestronk's studies suggested that titers greater than 1:10,000, with no cross-reactivity to GM1 ganglioside, have specificity for this syndrome. However, since that report, GALOP syndrome is now considered a variant of the antisulfatide syndrome, as the initially unknown antigen that copurified with myelin associated glycoprotein was subsequently determined to be sulfatide (Donofrio 2003; Kornberg and Pestronk 2003). Clinical manifestations Presentation and course Patients with antisulfatide antibodies usually present with an insidious onset, slowly progressive, distal and symmetrical sensory or sensorimotor neuropathy, affecting the legs and arms. Sensory disturbances may involve all modalities (or predominantly the small fibers) and are usually found in a stocking and glove distribution. Muscle weakness is usually mild and affects the distal muscles or is absent (Nemni et al 1993; Lopate et al 1997a; Van den Berg 1998; Erb et al 2000). A few reported patients with elevated antisulfatide antibodies had Guillain-Barré syndrome

2 or chronic inflammatory demyelinating polyradiculoneuropathy. Some patients with IgM anti-sulfatide antibodies and accompanying IgM paraproteinemia may have an ataxic gait disorder or tremor. Presence of high titers (greater than 1:4000) of IgM antisulfatide antibodies has an 80% to 90% specificity for a sensory rather than motor neuropathy syndrome (Kornberg and Pestronk 2003). In a study of 23 patients with significantly elevated antisulfatide antibodies (greater than 1:25,600) and polyneuropathy, 8 patients had predominantly small fiber neuropathy; 5 had mixed smalland large-fiber axonal sensory neuropathy; 7 had sensorimotor axonal neuropathy; and 3 had chronic inflammatory demyelinating polyradiculoneuropathy. Pain was a prominent symptom in 10 patients (Dabby et al 2000). In a series of 9 neuropathy patients with high antisulfatide titers, 1 patient had an asymmetric predominantly motor neuropathy (Erb et al 2000). Some have questioned the diagnostic utility of this test. Giannotta and colleagues reviewed 39 cases that had both high sulfatide antibodies and neuropathy (Giannotta et al 2015). Thirty-three (85%) had coincident myelin-associated glycoprotein antibodies (MAG), and the authors concluded that the sulfatide added questionable value. However, there were 6 others that had elevated sulfatide titers and various forms of neuropathy, including 1 with very high sulfatide titer, IgM gammopathy, demyelinating neuropathy, and negative anti-mag. Similarly, Campagnolo and colleagues reported 23 patients with chronic, distal, symmetric, slowly progressive polyneuropathy and predominant sensory impairment; most had underlying hematological disorders (Campagnolo et al 2015). Most patients had IgM monoclonal gammopathy of undetermined significance, 4 had Waldenstrom, 1 had non-hodgkin lymphoma, and 2 had no underlying disease. Of this group, 15 had high MAG antibody titers, 4 had isolated high antisulfatide titers, and 4 had high titers to both antibodies. Response to rituximab did not appear to correlate with the antibody pattern. GALOP syndrome is a progressive disabling gait disorder in the elderly (Pestronk et al 1993). In a study of 9 patients, Pestronk and colleagues reported gait ataxia and a distal sensory-predominant sensorimotor polyneuropathy. All sensory modalities may be impaired. Weakness is mild and mainly involves distal leg musculature (Pestronk et al 1994). Sulfatide measures, mainly in urine, are an important marker of metachromatic leukodystrophy. Neuropathy is a common manifestation. Dali and colleagues studied 13 children in Denmark with metachromatic leukodystrophy, 11 of which had evidence of neuropathy (Dali et al 2015). Sural nerve and CSF sulfatide levels were studied. Nerve levels correlated with peripheral but CSF levels did not correlate with central disease severity. Prognosis and complications The neuropathy associated with antisulfatide antibodies is usually slowly progressive. Pain can be a disabling symptom (Van den Berg 1998; Dabby et al 2000). If an IgM monoclonal gammopathy is present, then Waldenstrom macroglobulinemia or chronic lymphocytic leukemia should be considered, although most of the monoclonal gammopathies are classified as monoclonal gammopathy of uncertain significance. Biological basis Etiology and pathogenesis The cause for the development of antisulfatide antibodies and their role in the pathogenesis of the neuropathy are unknown. The role of antisulfatide antibodies in the pathogenesis of neuropathy is not yet understood. It seems unlikely that these antibodies are simply a secondary response to axonal damage; sulfatide is a major component of myelin. Patients with widespread axonal degeneration do not generally have high titers of these antibodies. The specificity of the antibody reactivity and the occurrence of monoclonal antibodies in a substantial number of patients suggest that humoral processes play a role in the pathogenesis. Mice deficient in sulfatide by knockout of cerebroside sulfotransferase enzyme develop severe neurologic abnormalities and disruption of both central and peripheral myelin, especially in paranodal regions; the mice have slow sciatic nerve conduction velocity (Hayashi et al 2013). Antisulfatide antibodies have been reported in a variety of neurologic disorders; however, significantly elevated titers (greater than 1:12,800) were closely associated with neuropathy (Quattrini et al 1992). A 1:4,000 titer for IgM antisulfatide antibodies was found to be the threshold titer for autoimmune peripheral neuropathy (Isoardo et al 2001). These antibodies have been reported to bind to the surface of dorsal root ganglia neurons and peripheral nerve myelin and axons, where they might exert their effect (Quattrini et al 1992; Lopate et al 1997b; Petratos et al 1999a). The

3 pattern of binding has been found to correlate with the type of neuropathy (Lopate et al 1997b). It seems that antibodies against sulfatide, which is expressed in myelin and axonal membranes, bind to various antigenic epitopes, producing different types of neuropathy. Axonal, demyelinating, or mixed neuropathies have all been described with antisulfatide antibodies. However, axonal predominantly sensory neuropathy is most common. In 1 study of patients with antisulfatide antibodies and demyelinating neuropathy, deposits of IgM and complement were seen on myelin sheaths in peripheral nerve biopsies; in another study passive transfer of antisulfatide antibodies was reported to induce demyelination in experimental rabbits (Nardelli et al 1995; Ferrari et al 1998). However, similar findings have not been reported in nerves or sera from patients with axonal neuropathies. Sera from patients with antisulfatide antibodies can cross react with or contain antibodies to myelin-associated glycoprotein or possibly unidentified nerve antigens (Pestronk et al 1991; Ilyas et al 1992). In a series of 25 patients with antisulfatide antibody titers greater than 1:25,600, two patients with axonal neuropathy had pathological findings of primary demyelination in addition to axonal degeneration, suggesting that both processes can occur in the same nerves. However, neither had detectable deposits of IgM or complement proteins (Dabby et al 2000). Antisulfatide antibodies (IgM and IgG) show increased titers in some rheumatological conditions, including systemic lupus erythematosus, antineutrophil cytoplasmic antibody-related small vessel vasculitis, mixed cryoglobulinemia, and Sjögren's syndrome; these increases may be nondiagnostic or associated with neuropathy (Alpa et al 2007). Monoclonal proteins are detected in some patients. Dabby and colleagues found a monoclonal gammopathy in 30% of patients (Dabby et al 2000). Interestingly, monoclonal antibodies were detected in patients with axonal sensory, sensorimotor and demyelinating neuropathies, but not in patients with small fiber neuropathy. Total IgM was elevated in one-half of the patients. In another published study of patients with antisulfatide antibodies, monoclonal gammopathy was closely associated with demyelination rather than axonal degeneration (Lopate et al 1997a). Demyelinating neuropathy with antisulfatide antibodies and monoclonal gammopathy was also reported in other small series (Carpo et al 2000; Petratos et al 2000). Eurelings and colleagues analyzed whether the presence of antisulfatide antibodies influences the outcome of polyneuropathy associated with IgM monoclonal gammopathy (Eurelings et al 2001). This study involved 65 patients in whom known causes of neuropathy were excluded. Although antisulfatide titers were elevated in 25 patients, the antibodies did not impact the clinical course, leading the authors to conclude that antisulfatide activity in IgM paraprotein-associated neuropathies does not have prognostic value. Farhad and colleagues analyzed a large series of patients diagnosed to have idiopathic neuropathy and assessed for overlooked underlying causes (Farhad et al 2016). One case out of 284 (0.3%) was found to have associated high antisulfatide titers. Epidemiology" Early studies detected antisulfatide antibodies in approximately one-quarter of patients with predominantly sensory polyneuropathy that otherwise would have been classified as idiopathic (Pestronk et al 1991; Nemni et al 1993). However, later studies did not duplicate such a high frequency of antisulfatide activity in this common patient population, suggesting that no more than 1% to 2% of patients with chronic unclassified sensory or sensorimotor polyneuropathies had antisulfatide antibodies (Wolfe and Nations 2001). The gender ratio for antisulfatide associated neuropathies remains unclear. Dabby has reported a male to female ratio of 1:1.3 (Dabby et al 2000). In Erb's series the male to female ratio was 7:4 (Erb et al 2000). Differential diagnosis Antisulfatide associated neuropathy shares common features with other types of chronic neuropathies. Diabetic polyneuropathy, which is typically slowly progressive, predominantly sensory, and often painful, may resemble antisulfatide neuropathy. In rare cases, patients with diabetes and neuropathy have been reported to have antisulfatide antibodies, but measured titers were low (Shigeta et al 1997). Toxic or drug-induced polyneuropathies can be distinguished from antisulfatide neuropathy by a careful medical history, and improvement or stabilization after withdrawal of the offending agent. Neuropathies associated with vitamin deficiencies or metabolic disorders such as renal, hepatic, or thyroid dysfunction can be reliably diagnosed with laboratory testing. Other immune-associated neuropathies can closely resemble antisulfatide neuropathy. Antimyelin associated glycoprotein neuropathy is characterized by markedly slow nerve conduction velocities, prolonged distal latencies, and an IgM monoclonal gammopathy in most patients. Chronic inflammatory demyelinating neuropathy usually involves both motor and sensory nerves and commonly presents with distal and proximal weakness. CSF protein is

4 characteristically high in chronic inflammatory demyelinating polyradiculoneuropathy and electrodiagnostic studies show a demyelinating pattern. Paraneoplastic neuropathies can be secondary to solid tumors such as small cell lung carcinoma. Identifying the primary tumor or detection of humoral factors such as anti-hu antibodies leads to the correct diagnosis. Study of autoantibodies in patients with active celiac disease found low levels of various IgG and IgM ganglioside antibodies. Sulfatide IgG (36%) and IgA (19%) were found. On a strict gluten-free diet the IgG antibodies resolved whereas IgA persisted in 2 cases, although correlation with neurologic symptoms was not clearly established (Saccomanno et al 2017). This link also reinforces the utility of screening neuropathy patients for celiac disease. Diagnostic workup Nerve conduction studies usually show features of axonal sensory or sensorimotor neuropathy (Nemni et al 1993; Van den Berg 1998). In some patients there is a predominantly demyelinating neuropathy with slow conduction velocities and dispersed potentials (Nardelli et al 1995; Lopate et al 1997a; Melendez-Vasquez et al 1997; Carpo et al 2000; Petratos et al 2000). In patients with predominantly small fiber neuropathy, conduction studies may be normal. In those patients, quantitative sensory testing may show selective small fiber involvement (Pestronk et al 1991; Quattrini et al 1992; Dabby et al 2000). The neuropathy associated with the GALOP syndrome appears to be heterogeneous. Some features suggesting demyelination are found in 80% of patients. Prolonged distal latencies and slow conduction velocities are commonly seen, although conduction block is not evident. Information about the pathological changes in the nerves of patients with neuropathy and elevated antisulfatide antibodies is limited. Biopsy studies can reveal normal histology, axonal degeneration, or demyelination (Quattrini et al 1992; Nemni et al 1993; Lopate et al 1997b; Ferrari et al 1998). In 1 series, 2 patients with axonal neuropathy had pathological findings of primary demyelination (ie, thinly myelinated fibers and small onion bulbs). These findings were superimposed over evidence of axonal degeneration (Dabby et al 2000). Antisulfatide antibodies are most reliably detected by enzyme-linked immunosorbent assay, using sulfatide as the antigen. Several factors increase the likelihood of a positive test such as age greater than 50 years, disability from neuropathic symptoms, gait disorder, tremor, electrophysiologic evidence of demyelination, and IgM monoclonal gammopathy (Pestronk 2002). Detection of the monoclonal protein, which occurs in a substantial number of patients, is best done by serum protein immunoelectrophoresis or immunofixation electrophoresis. If a monoclonal protein is present, then a bone marrow biopsy is indicated to rule out Waldenstrom macroglobulinemia. Management There is little information to guide the management of neuropathies associated with antisulfatide antibodies or the GALOP syndrome. Patients with demyelinating features are treated similarly to those with chronic inflammatory demyelinating polyradiculopathy. Pain management is often the focus for patients with painful, small fiber presentations; they may respond to antidepressants or anticonvulsants used for other causes of neuropathic pain. Patients with monoclonal gammopathies should be evaluated for the presence of a B-cell lymphoproliferative disorder. Pestronk and colleagues treated a few patients with GALOP syndrome successfully using immunomodulators such as intravenous gammaglobulin, plasmapheresis, and cyclophosphamide (Pestronk et al 1993). References cited Alpa M, Ferrero B, Cavallo R, et al. Anti-GM1 and anti-sulfatide antibodies in patients with systemic lupus erythematosus, Sjögren's syndrome, mixed cryoglobulinemia and idiopathic systemic vasculitis. Clin Exp Rheumatol 2007;25(4): PMID Campagnolo M, Ferrari S, Dalla Torre C, et al. Polyneuropathy with anti-sulfatide and anti-mag antibodies: clinical, neurophysiological, pathological features and response to treatment. J Neuroimmunol 2015;281:1-4. PMID Carpo M, Meucci N, Allaria S, et al. Anti-sulfatide antibodies in peripheral neuropathy. J Neurol Sci 2000;176: PMID

5 Dabby R, Weimer LH, Hays AP, Olarte M, Latov N. Anti-sulfatide antibodies in neuropathy: clinical and electrophysiologic correlates. Neurology 2000;54: PMID Dali CÍ, Barton NW, Farah MH, et al. Sulfatide levels correlate with severity of neuropathy in metachromatic leukodystrophy. Ann Clin Transl Neurol 2015;2(5): PMID Donofrio PD. Immunotherapy of idiopathic inflammatory neuropathies. Muscle Nerve 2003;28(3): PMID Erb S, Ferracin F, Fuhr P, et al. Polyneuropathy attributes: a comparison between patients with anti-mag and antisulfatide antibodies. J Neurol 2000;247: PMID Eurelings M, Moons KG, Notermans NC, et al. Neuropathy and IgM M-proteins. Prognostic value of antibodies to MAG, SGPG, and sulfatide. Neurology 2001;56: PMID Farhad K, Traub R, Ruzhansky KM, Brannagan TH 3rd. Causes of neuropathy in patients referred as "idiopathic neuropathy". Muscle Nerve 2016;53(6): PMID Ferrari S, Morbin M, Nobile-Orazio E, et al. Antisulfatide polyneuropathy: antibody- mediated complement attack on peripheral myelin. Acta Neuropathol 1998;96(6): PMID Fredman P, Lycke J, Andersen O, Vrethem M, Ernerudh J, Svennerholm L. Peripheral neuropathy associated with monoclonal IgM antibody to glycolipids with a terminal glucuronyl-3-sulfate epitope. J Neurol 1993;240: PMID Fredman P, Vedeler CA, Nyland H, Aarli JA, Svennerholm L. Antibodies in sera from patients with inflammatory demyelinating polyradiculoneuropathy react with ganglioside LM1 and sulphatide of peripheral nerve myelin. J Neurol 1991;238:75-9. PMID Giannotta C, Di Pietro D, Gallia F, Nobile-Orazio E. Anti-sulfatide IgM antibodies in peripheral neuropathy: to test or not to test? Eur J Neurol 2015;22(5): PMID Hayashi A, Kaneko N, Tomihira C, Baba H. Sulfatide decrease in myelin influences formation of the paranodal axo-glial junction and conduction velocity in the sciatic nerve. Glia 2013;61(4): PMID Ilyas AA, Cook SD, Dalakas MC, Mithen FA. Anti-MAG IgM paraproteins from some patients with polyneuropathy associated with IgM paraproteinemia also react with sulfatide. J Neuroimmunol 1992;37: PMID Ilyas AA, Mithen FA, Dalakas MC, et al. Antibodies to sulfated glycolipids in Guillain-Barre syndrome. J Neurol Sci 1991;105: PMID Isoardo G, Ferrero B, Barbero P, et al. Anti-GM1 and anti-sulfatide antibodies in polyneuropathies. Acta Neurol Scand 2001;103: PMID Kornberg AJ, Pestronk A. Antibody-associated polyneuropathy syndromes: principles and treatment. Semin Neurol 2003;23(2): PMID Latov N. Pathogenesis and therapy of neuropathies associated with monoclonal gammopathies. Ann Neurol 1995;37:S PMID Lopate G, Parks BJ, Goldstein JM, Yee WC, Friesenhahn GM, Pestronk A. Polyneuropathies associated with high titre antisulfatide antibodies: Characteristics of patients with and without serum monoclonal proteins. J Neurol Neurosurg Psychiatry 1997a;62: PMID Lopate G, Pestronk A, Evans S, Li L, Clifford D. Anti-sulfatide antibodies in HIV-infected individuals with sensory neuropathy. Neurology 2005;64(9): PMID Lopate G, Pestronk A, Kornberg AJ, Yue J, Choksi R. IgM anti-sulfatide autoantibodies: patterns of binding to cerebellum, dorsal root ganglion and peripheral nerve. J Neurol Sci 1997b;151: PMID

6 Melendez-Vasquez C, Redford J, Choudhary PP, et al. Immunological investigation of chronic inflammatory demyelinating polyradiculoneuropathy. J Neuroimmunol 1997;73: PMID Nardelli E, Bassi A, Mazzi G, Anzini P, Rizzuto N. Systemic passive transfer studies using IgM monoclonal antibodies to sulfatide. J Neuroimmunol 1995;63: PMID Nemni R, Fazio R, Quattrini A, Lorenzetti I, Mamoli D, Canal N. Antibodies to sulfatide and chondroitin sulfate C in patients with chronic sensory neuropathy. J Neuroimmunol 1993;43: PMID Nobile-Orazio E, Manfredini E, Carpo M. et al. Frequency and clinical correlates of anti-neural IgM antibodies in neuropathy associated with IgM monoclonal gammopathy. Ann Neurol 1994;36: PMID Pestronk A. Autoantibodies and immune polyneuropathies. In: Katirji B, Kaminski HJ, Preston DC, Ruff RL, Shapiro BE, editors. Neuromuscular disorders in clinical practice. Woburn: Butterworth-Heinemann, 2002: Pestronk A, Choksi R, Bieser K, et al. GALOP syndrome: a treatable autoimmune gait disorder with late-age onset. Ann Neurol 1993;34: 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: PMID Pestronk A, Li F, Griffin J, et al. Polyneuropathy syndromes associated with serum antibodies to sulfatide and myelinassociated glycoprotein. Neurology 1991;41: PMID Petratos S, Turnbull VJ, Papadopoulos R, Ayers M, Gonzales MF. Peripheral nerve binding pattern of anti-sulfatide antibodies in HIV-infected individuals. NeuroReport 1999a;10: PMID Petratos S, Turnbull VJ, Papadopoulos R, Ayers M, Gonzales MF. High titer anti-sulfatide antibodies in HIV-infected individuals. NeuroReport 1999b;10: PMID Petratos S, Turnbull VJ, Papadopoulos R, Ayers M, Gonzales MF. High-titre IgM anti-sulfatide antibodies in individuals with IgM paraproteinemia and associated peripheral neuropathy. Immunol Cell Biol 2000;78(2): PMID Quattrini A, Corbo M, Dhaliwal SK, et al. Anti-sulfatide antibodies in neurological disease: binding to rat dorsal root ganglia neurons. J Neurol Sci 1992;112: PMID Ryberg B. Multiple specificities of antibrain antibodies in multiple sclerosis and chronic myelopathy. J Neurol Sci 1978;38: PMID Saccomanno D, Tomba C, Magri F, et al. Anti-sulfatide reactivity in patients with celiac disease. Scand J Gastroenterol 2017;52(4): PMID Shigeta H, Yamaguchi M, Nakano K, et al. Serum antibodies against sulfatide and phospholipid in NIDDM patients with diabetic neuropathy. Diabetes Care 1997;20: PMID 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: PMID Van den Berg LH. Neuropathies associated with anti-sulfatide and other glycoconjugate antibodies. In: Latov N, Wokke JH, Kelly Jr JJ, editors. Immunological and infectious diseases of the peripheral nerves. Cambridge : Cambridge University Press, 1998: Van den Berg LH, Lankamp CL, de Jager AE, et al. Anti-sulphatide antibodies in peripheral neuropathy. J Neurol Neurosurg Psychiatry 1993;56: PMID van Vliet 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(1): PMID Wolfe GI, Nations SP. Guide to autoantibody testing in peripheral neuropathies. Neurologist 2001;7:

7 **References especially recommended by the author or editor for general reading. Former authors Ron A Dabby MD and Norman Latov MD PhD (original authors), Jaya R Trivedi MD, Gil I Wolfe MD ICD and OMIM codes ICD codes ICD-9: Unspecified idiopathic peripheral neuropathy: ICD-10: Hereditary and idiopathic neuropathy, unspecified: G60.9 Profile Age range of presentation years years 65+ years Sex preponderance male=female Family history none Heredity none Population groups selectively affected none selectively affected Occupation groups selectively affected none selectively affected Differential diagnosis list diabetic polyneuropathy diabetes toxic polyneuropathies drug-induced polyneuropathies neuropathies associated with vitamin deficiencies neuropathies associated with metabolic disorders immune-associated neuropathies antimyelin associated glycoprotein neuropathies chronic inflammatory demyelinating neuropathies cancer small lung cell carcinoma anti-hu antibodies celiac disease

8 Associated disorders GALOP syndrome Neuropathy associated with antimyelin associated glycoprotein antibodies Other topics to consider Chronic inflammatory demyelinating polyradiculoneuropathy Idiopathic sensory and sensorimotor neuropathies Neuropathies associated with monoclonal gammopathies Polyneuropathy associated with anti-mag IgM antibodies Copyright MedLink Corporation. All rights reserved.