Clinical and laboratory assessment of distal peripheral nerves in Gulf War veterans and spouses.

Background: The prevalence of symptoms suggesting distal symmetric polyneuropathy (DSP) was reported to be higher among deployed veterans (DV) to the Persian Gulf in 1990-1991 than to control non-deployed veterans (NDV). The authors therefore compared the prevalence of DSP by direct examination of DV and their spouses to control NDV and spouses.

Methods: The authors performed standardized neurologic examinations on 1,061 DV and 1,128 NDV selected from a cohort of veterans who previously participated in a national mail and telephone survey.

Immunoglobulin G subclass distribution of autoantibodies to gangliosides in patients with Guillain-Barre syndrome.

IgG anti-ganglioside antibodies are present in a proportion of patients with the Guillain-Barré syndrome (GBS). To determine if antibodies to gangliosides are restricted in IgG subclass distribution, we evaluated IgG subclass antibody responses to gangliosides in sera of patients with GBS. Sera from GBS patients with IgG activity against gangliosides were analyzed for IgG subclass distribution using an enzyme-linked immunosorbent assay.

Antibodies to GT1a ganglioside in patients with Guillain-Barré syndrome.

Serum antibodies from 8 (13%) of 62 patients with the acute Guillain-Barré syndrome (GBS) and 1 of 3 patients with the Miller Fisher syndrome (MFS) recognized a minor ganglioside in bovine and human brain trisialoganglioside fractions. The ganglioside antigen migrated between GD1a and GD1b on thin-layer chromatograms. The structure of this ganglioside was established to be GT1a by thin-layer chromatography blotting and mass spectrometry.

Serologic evidence of previous Campylobacter jejuni infection in patients with the Guillain-Barré syndrome.

Objective: To determine if patients with the Guillain-Barré syndrome are likely to have had Campylobacter jejuni infection before onset of neurologic symptoms.

Design: A case-control study.

Setting: Several university medical centers.

Elevated neopterin levels in Guillain-Barré syndrome. Further evidence of immune activation.

Neopterin is a by-product of guanosine triphosphate metabolism and is produced by macrophages in response to lymphocytic activation. We have studied serum neopterin levels in patients with Guillain-Barré syndrome to obtain further evidence of immune activation in this disease. Serum neopterin levels were significantly elevated in patients with Guillain-Barré syndrome compared with patients with other peripheral neuropathies and multiple sclerosis and with healthy control subjects.

Effects of Guillain-Barré sera containing antibodies against glycolipids in cultures of rat Schwann cells and sensory neurons.

Serum samples from 52 patients with the acute Guillain-Barré syndrome (GBS), 19 patients with other neurological disorders, and 18 healthy volunteers were tested for cytotoxicity in cultures of rat Schwann cells and dorsal root ganglion neurons. The samples were also examined by enzyme-linked immunosorbent assay for IgG and IgM antibodies against various acidic and neutral glycolipids. Samples from 16 of the 52 (31%) acute GBS patients and from 1 of the 6 patients with chronic inflammatory demyelinating polyneuropathy produced myelin breakdown in culture.

Anti-MAG IgM paraproteins from some patients with polyneuropathy associated with IgM paraproteinemia also react with sulfatide.

Sera from five of 11 patients with neuropathy associated with IgM paraproteinemia (NAIgMPP) and reactivity against myelin-associated glycoprotein (MAG) also had elevated levels of IgM against sulfatide. Although three patients had anti-sulfatide IgM titers of less than or equal to 1:1000, two patients had titers of greater than or equal to 1:50,000. Absorption of patient serum with sulfatide revealed that anti-MAG IgM paraproteins in two patients with high titer anti-sulfatide IgM crossreacted with sulfatide.

Anti-GM1 IgA antibodies in Guillain-Barré syndrome.

Serum anti-GM1 IgA antibodies were detected in 15 of 53 (28%) patients with the acute Guillain-Barré syndrome (GBS) and in one of 26 (4%) patients with other neurological diseases. Although nine GBS patients had anti-GM1 IgA titers of 1:200 or less, six patients had titers of 1:800 or more. Some GBS patients with anti-GM1 IgA antibodies also had antibodies against GD1b or GM2 or both.

Antibodies to acidic glycolipids in Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy.

Using an enzyme-linked immunosorbent assay and a thin-layer chromatography-immunostaining procedure, we detected serum antibodies against acidic glycolipids in 36 of 53 patients with Guillain-Barré syndrome (GBS) and 8 of 16 patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Although we also found anti-acidic glycolipid antibodies in 4 of 13 patients with other neurological diseases; 2 of 10 patients with multiple sclerosis; 8 of 33 patients with inflammatory, infectious, allergic or autoimmune disorders and 3 of 32 healthy subjects, the levels of antibodies in these controls were much lower than in GBS patients. There were several patterns of reactivity of GBS sera including antibodies to LM1 and HexLM1, GM1 or GD1b or both, various other gangliosides, sulfated glycolipids, and as yet unidentified glycolipids.

Antibodies to sulfated glycolipids in Guillain-Barré syndrome.

Sera from 53 patients with acute Guillain-Barré syndrome (GBS), 15 patients with chronic inflammatory demyelinating polyneuropathy (CIDP), 13 patients with other neurological diseases (OND) and 31 healthy controls were tested for IgM and IgG antibodies to sulfoglucuronyl paragloboside (SGPG) and sulfatide by both an ELISA and a thin-layer chromatogram-overlay technique. Although the mean levels of anti-SGPG or anti-sulfatide antibodies in GBS patients were not elevated compared to controls, the occurrence of anti-SGPG antibodies was more frequent in GBS patients than in controls (P less than 0.02).

Clinical correlation with serum-soluble interleukin-2 receptor levels in Guillain-Barré syndrome.

In patients with Guillain-Barré syndrome (GBS) soluble interleukin-2 receptor (sIL-2R) levels were elevated compared with those of patients with other neurologic diseases (OND), and of healthy controls. Smaller increases in sIL-2R levels occurred in OND patients compared to healthy subjects. Monitoring of GBS patients clearly demonstrated that decreases in sIL-2R levels correlated with clinical recovery.

Search for antibodies to neutral glycolipids in sera of patients with Guillain-Barré syndrome.

Sera from 54 patients with Guillain-Barré syndrome (GBS), 34 patients with other neurological diseases (OND) and 32 healthy controls were tested for antibodies to total lipid fractions and higher neutral glycolipid fractions isolated from human and dog nerves, purified Forssman glycolipid and a panel of purified neutral glycolipids by both an enzyme-linked immunosorbent assay (ELISA) and a thin-layer chromatogram (TLC)-overlay technique. IgM and IgG antibodies to total lipid fractions, as well as to galactocerebroside, ceramide dihexoside, ceramide trihexoside, and globoside were not significantly elevated in the sera of GBS patients as compared to controls. High levels of anti-asialo-GM1 IgG antibodies, however, were detected in 6 of 54 (11%) GBS patients and 1 of 30 (3%) OND patients.

Human alpha tumor necrosis factor does not damage cultures containing rat Schwann cells and sensory neurons.

The effects of recombinant human alpha tumor necrosis factor (alpha-TNF) were compared with those of cytotoxic serum from patients with the acute Guillain-Barré syndrome (GBS) in myelinated cultures containing only rat Schwann cells and dorsal root ganglion neurons. Alpha-TNF did not damage rat peripheral nervous system tissue in culture. These observations suggest that alpha-TNF is not responsible for the cytotoxic activity of acute GBS serum in culture.

Effects of A23187 in cultures containing only rat Schwann cells and sensory neurons.

Serum from approximately 40% of patients with the acute Guillain-Barré syndrome (GBS) selectively destroys myelin and myelin-related Schwann cells in cultures containing only rat dorsal root ganglion neurons and Schwann cells. To determine if the effects of GBS serum on myelin and myelin-related Schwann cells could be mediated through elevations in the intracellular concentration of calcium ions, we compared the effects of cytotoxic serum to A23187, a divalent cation ionophore. Both myelin- and nonmyelin-related Schwann cells were killed along with neurons in the presence of A23187 and extracellular calcium ions.

Effects of ethanol on rat Schwann cell proliferation and myelination in culture.

It is possible to treat dissociated embryonic rat dorsal root ganglia in culture to inhibit proliferation of all nonneuronal cells except Schwann cells. Neurons have been shown to produce a mitogenic stimulus for Schwann cells under these conditions. Additionally, myelin-competent neurons induce Schwann cells to elaborate myelin sheaths.

Ultrastructural effects of Guillain-Barré serum in cultures containing only rat Schwann cells and dorsal root ganglion neurons.

Serum from patients with the acute form of the Guillain-Barré syndrome was applied to cultures containing only rat dorsal root ganglion neurons and Schwann cells. Serum taken from 4 of 10 patients during the first 1-3 weeks of clinical onset had previously been shown to have significant demyelinating activity in this culture system when observed at the light microscopic level. More detailed assessment made at the ultrastructural level showed that: (1) wide-spread myelin-related Schwann cell lysis occurred in concert with vesicular myelin breakdown; (2) non-myelin-related Schwann cells avidly phagocytized necrotic cell debris and fragments of compact myelin; and (3) neurites and non-myelin-related Schwann cells remained structurally undamaged.

Immunohistochemical study of myelin sheaths formed by oligodendrocytes interacting with dissociated dorsal root ganglion neurons in culture.

The addition of central nervous system (CNS) glial cells to dissociated networks of rat dorsal root ganglion neurons in tissue culture provided a useful system for the study of CNS myelin sheath formation. The CNS myelin basic proteins (BP) and proteolipid protein (PLP) were demonstrable in these cultures by immunoperoxidase techniques. Both BP and PLP were detectable in myelinating oligodendrocytes and CNS myelin sheaths.

Factors affecting schwann cell basal lamina formation in cultures of dorsal root ganglia from mice with muscular dystrophy.

Pure populations of sensory neurons (N), Schwann cells (S) and fibroblasts (Fb) were established in culture from normal and dystrophic (dy) mice in order to investigate the cellular origin(s) of the peripheral nervous system abnormalities present in murine muscular dystrophy. These cell types were placed together in various combinations and their subsequent interactions were monitored with the light and electron microscope. The formation of the basal lamina (BL) which in normal tissue, completely surrounds the external aspect of the Schwann cell (when in contact with axons) was documented by morphometric analysis of electron micrographs.

Studies with antisera against peripheral nervous system myelin and myelin basic proteins. II. Immunohistochemical studies in cultures of rat dorsal root ganglion neurons and Schwann cells.

Antiserum against rat peripheral nervous system (PNS) myelin contained immunoglobulins which bound preferentially to the extracellular surfaces of myelin-related Schwann cells in intact cultures of dorsal root ganglion (DRG) neurons and Schwann cells, while antiserum against basic protein (BP) from central nervous system myelin or the PNS basic protein P2 did not. We demonstrate the presence of PNS myelin proteins P1 (identical to BP) and P2 by immunoperoxidase techniques in DRG cultures that had been treated to disrupt cellular membranes. These observations suggest that P1 and P2 are not exposed on the extracellular surfaces of myelin-related Schwann cells in culture.

Studies with antisera against peripheral nervous system myelin and myelin basic proteins. I. Effects of antiserum upon living cultures of nervous tissue.

We studied the effects of antiserum against rat peripheral nervous system (PNS) myelin, rat or chicken central nervous system myelin basic protein (BP), or rabbit P2 protein from PNS myelin on myelinated cultures containing only rat dorsal root ganglion neurons and Schwann cells. While anti-PNS myelin serum consistently produced segmental PNS demyelination, anti-BP serum and anti-P2 serum did not. The culture results suggest that the myelin PNS proteins P1 (identical to basic protein from central nervous system myelin) and P2 are not exposed on the extracellular surfaces of myelin-related Schwann cells in tissue culture.

Expression of the trembler mouse mutation in organotypic cultures of dorsal root ganglia.

Organotypic dorsal root ganglion (DRG) cultures were established from all the embryos of two trembler (Tr/+) female mice mated to normal (+/+) males to determine if the trembler mutation would be expressed in nerve tissue culture. Dorsal root ganglia from normal mice maintained in our culture system exhibit substantial myelination after 6 weeks of growth. This normal pattern was observed in approximately one half of the cultures in the present series.

Proteolipid protein antiserum does not affect CNS myelin in rat spinal cord culture.

Sera from 3 rabbits and 1 goat which contained precipitating antibodies to highly purified rat CNS myelin proteolipid protein (PLP) did not inhibit CNS myelin formation nor destroy intact CNS myelin in cultures of rat spinal cord. CNS myelin which formed in the presence of antiPLP serum and complement appears ultrastructurally identical to myelin formed in normal control cultures. The lack of demyelinating and myelin formation inhibiting activities in antisera to PLP suggests either: (1) PLP is not exposed on the external surface of the myelin membrane; or (2) the externally exposed portions of PLP were rendered nonantigenic during the purification of PLP.