chondroitin-sulfates and Peripheral-Nervous-System-Diseases

Approximately 10% of patients with peripheral neuropathy of otherwise unknown etiology have an associated monoclonal gammopathy. Both the neuropathies and the monoclonal gammopathies in these patients are heterogeneous, but several distinct clinical syndromes that may respond to specific therapies can be recognized. It is important to recognize these syndromes because monoclonal gammopathies also occur in 1% of the normal adult population, and in some cases, monoclonal gammopathies are coincidental and unrelated to the neuropathy. In patients with IgM monoclonal gammopathies, IgM M proteins frequently have autoantibody activity and are implicated in the pathogenesis of the neuropathy. IgM M proteins that bind to myelin-associated glycoprotein (MAG) have been shown to cause demyelinating peripheral neuropathy; anti-GM1 antibody activity is associated with predominantly motor neuropathy, and anti-sulfatide or chondroitin sulfate antibodies are associated with sensory neuropathy. The IgM monoclonal gammopathies may be malignant or nonmalignant, and polyclonal antibodies with the same specificities are associated with similar clinical presentations in the absence of monoclonal gammopathy. IgG or IgA monoclonal gammopathies are associated with neuropathy in patients with osteosclerotic myeloma or the POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy myeloma, and skin changes). Amyloidosis or cryoglobulinemic neuropathies can occur with either IgM or IgG and IgA monoclonal gammopathies. Therapeutic intervention depends on the specific clinical syndrome but is generally directed at removing the autoantibodies, reducing the number of monoclonal B cells, and interfering with the effector mechanisms.

Topics: Adult; Aged; Amyloidosis; Antibody Specificity; Antineoplastic Agents; Autoantibodies; Autoantigens; Autoimmune Diseases; Chondroitin Sulfates; Gangliosides; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunoglobulins, Intravenous; Middle Aged; Myelin-Associated Glycoprotein; Paraneoplastic Syndromes; Paraproteinemias; Paraproteins; Peripheral Nervous System Diseases; Plasmapheresis; Sulfoglycosphingolipids

Topics: Back Pain; Balneology; Chondroitin Sulfates; Combined Modality Therapy; Humans; Intervertebral Disc; Nerve Compression Syndromes; Osteochondritis; Papain; Peripheral Nervous System Diseases; Radiography; Spinal Diseases

Bioabsorbable unfilled synthetic nerve conduits have been used in the reconstruction of small segmental nerve defects with variable results, especially in motor nerves. We hypothesized that providing a synthetic mimic of the Schwann cell basal lamina in the form of a collagen-glycosaminoglycan (GAG) matrix would improve the bridging of the nerve gap and functional motor recovery.. A unilateral 10-mm sciatic nerve defect was created in eighty-eight male Lewis rats. Animals were randomly divided into four experimental groups: repair with reversed autograft, reconstruction with collagen nerve conduit (1.5-mm NeuraGen, Integra LifeSciences), reconstruction with collagen nerve conduit filled with collagen matrix, and reconstruction with collagen nerve conduit filled with collagen-GAG (chondroitin-6-sulfate) matrix. Nerve regeneration was evaluated at twelve weeks on the basis of the compound muscle action potential, maximum isometric tetanic force, and wet muscle weight of the tibialis anterior muscle, the ankle contracture angle, and nerve histomorphometry.. The use of autograft resulted in significantly better motor recovery compared with the other experimental methods. Conduit filled with collagen-GAG matrix demonstrated superior results compared with empty conduit or conduit filled with collagen matrix with respect to all experimental parameters. Axon counts in the conduit filled with collagen-GAG matrix were not significantly different from those in the reversed autograft at twelve weeks after repair.. The addition of the synthetic collagen basal-lamina matrix with chondroitin-6-sulfate into the lumen of an entubulation repair significantly improved bridging of the nerve gap and functional motor recovery in a rat model.. Use of a nerve conduit filled with collagen-GAG matrix to bridge a motor or mixed nerve defect may result in superior functional motor recovery compared with commercially available empty collagen conduit. However, nerve autograft remains the gold standard for reconstruction of a segmental motor nerve defect.

Topics: Absorbable Implants; Animals; Chondroitin Sulfates; Collagen; Disease Models, Animal; Electromyography; Glycosaminoglycans; Guided Tissue Regeneration; Male; Motor Skills; Nerve Regeneration; Peripheral Nerves; Peripheral Nervous System Diseases; Random Allocation; Rats; Rats, Inbred Lew; Recovery of Function; Reference Values; Sciatic Nerve; Transplantation, Autologous; Treatment Outcome

Adverse health effects of fungal bioaerosols on occupants of water-damaged homes and other buildings have been reported. Recently, it has been suggested that mold exposure causes neurological injury. The authors investigated neurological antibodies and neurophysiological abnormalities in patients exposed to molds at home who developed symptoms of peripheral neuropathy (i.e., numbness, tingling, tremors, and muscle weakness in the extremities). Serum samples were collected and analyzed with the enzyme-linked immunosorbent assay (ELISA) technique for antibodies to myelin basic protein, myelin-associated glycoprotein, ganglioside GM1, sulfatide, myelin oligodendrocyte glycoprotein, alpha-B-crystallin, chondroitin sulfate, tubulin, and neurofilament. Antibodies to molds and mycotoxins were also determined with ELISA, as reported previously. Neurophysiologic evaluations for latency, amplitude, and velocity were performed on 4 motor nerves (median, ulnar, peroneal, and tibial), and for latency and amplitude on 3 sensory nerves (median, ulnar, and sural). Patients with documented, measured exposure to molds had elevated titers of antibodies (immunoglobulin [Ig]A, IgM, and IgG) to neural-specific antigens. Nerve conduction studies revealed 4 patient groupings: (1) mixed sensory-motor polyneuropathy (n = 55, abnormal), (2) motor neuropathy (n = 17, abnormal), (3) sensory neuropathy (n = 27, abnormal), and (4) those with symptoms but no neurophysiological abnormalities (n = 20, normal controls). All groups showed significantly increased autoantibody titers for all isotypes (IgA, IgM, and IgG) of antibodies to neural antigens when compared with 500 healthy controls. Groups 1 through 3 also exhibited abnormal neurophysiologic findings. The authors concluded that exposure to molds in water-damaged buildings increased the risk for development of neural autoantibodies, peripheral neuropathy, and neurophysiologic abnormalities in exposed individuals.

Topics: Adult; Autoantibodies; Case-Control Studies; Chondroitin Sulfates; Environmental Exposure; Enzyme-Linked Immunosorbent Assay; Female; Fungi; G(M1) Ganglioside; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Male; Middle Aged; Mycotoxins; Myelin Proteins; Nerve Tissue Proteins; Neural Conduction; Neurofilament Proteins; Neuropsychological Tests; Peripheral Nervous System Diseases; Sick Building Syndrome; Sulfoglycosphingolipids; Surveys and Questionnaires; Tubulin; Water Microbiology

Sera from eight of 25 patients with chronic sensory neuropathy had high titers of antibodies to sulfatide and chondroitin sulfate C or both. Preclearing of patients' sera with either sulfatide or chondroitin sulfate C revealed that in four patients the antisulfatide antibodies crossreacted with chondroitin sulfate C. By indirect immunohistochemistry sera reactive to sulfatide only had a different staining pattern from those reactive to both sulfatide and chondroitin sulfate C. By direct immunohistochemistry we found immunoglobulins bound to nerve fibers only in patients with serum antibodies against both sulfatide and chondroitin sulfate C. Our study provides evidence that antibodies to sulfatide and to chondroitin sulfate C differ in their fine specificity and are present in 30% of patients with chronic sensory neuropathy.

Topics: Adult; Aged; Antibodies; Chondroitin Sulfates; Chronic Disease; Female; Humans; Immunohistochemistry; Male; Middle Aged; Neurons, Afferent; Peripheral Nervous System Diseases; Sulfoglycosphingolipids

We report a patient with a progressive, predominantly sensory neuropathy and a IgM kappa M-protein that binds to Schmidt-Lantermann incisures. A sural nerve biopsy showed primary axonal damage and IgM deposits at Schmidt-Lantermann incisures were seen by direct immunoperoxidase. Serum from the patient injected into rat sciatic nerve reacts with the incisures as with those in the patient's nerve. The IgM kappa M-protein reacts with chondroitin sulfate C and binds to a broad nerve protein band with a mobility of between 170 and 118 kDa. Peripheral neuropathy may be related to the M-protein, which had immunocytochemical reactivity not previously described for patients with polyneuropathy and IgM monoclonal gammopathy.

Topics: Axons; Blood Proteins; Chondroitin Sulfates; Humans; Immunoblotting; Immunoglobulin kappa-Chains; Immunoglobulin M; Immunoglobulins; Male; Middle Aged; Nerve Fibers, Myelinated; Peripheral Nervous System Diseases; Sural Nerve

In axonal neuropathies associated with IgM paraproteinemia, reports of antigen specificity of the M-protein are few. A patient with IgM paraproteinemia presented with progressive mononeuritis multiplex. IgM was found deposited in striking amounts in endoneurium and shown to bind specifically to neural proteins and chondroitin sulfates. Direct immune mechanisms, as well as the physical effects of IgM deposition, likely contributed to the development of the neuropathy.

Topics: Aged; Chondroitin Sulfates; Electrophoresis, Polyacrylamide Gel; Fluorescent Antibody Technique; Humans; Immunoglobulin M; Immunohistochemistry; Male; Microscopy, Electron; Nerve Tissue Proteins; Paraproteinemias; Peripheral Nerves; Peripheral Nervous System Diseases; Reference Values

We studied two patients with an axonal type of polyneuropathy, epidermolysis, and IgM kappa plasma cell dyscrasia. The IgM kappa was deposited in the dermis, was absorbed from the serum by axonal micelle preparations, and was precipitated with chondroitin sulfate in highly purified agarose in 0.15 M NaCl with 0.01 M phosphate buffer, pH 7.8. In contrast, we found none of these abnormalities in three patients with IgM plasma cell dyscrasia and demyelinating neuropathy. Of 78 other macroglobulinemic serum samples from patients without neuropathy, 7 precipitated with a sulfated polysaccharide. This reaction occurred at low ionic strength, 0.05 M barbital buffer, pH 8.1, but did not occur in the higher ionic strength of 0.01 M phosphate with 0.15 M NaCl (PBS). The interaction of the IgM with chondroitin sulfate at relatively high ionic strength could cause both the axonal polyneuropathy and the epidermolysis.

Topics: Absorption; Antibodies, Monoclonal; Axons; Chondroitin; Chondroitin Sulfates; Epidermolysis Bullosa; Female; Humans; Immunoglobulin kappa-Chains; Immunoglobulin M; Male; Middle Aged; Peripheral Nervous System Diseases; Sural Nerve