Treatment of the Guillain-Barré syndrome by plasmapheresis.

Treatment by plasmapheresis was performed in eight adult patients with the Guillain-Barré syndrome. One patient with a chronic relapsing form underwent four separate courses of plasmapheresis and her condition improved rapidly each time. Of seven patients with acute Guillain-Barré syndrome, the condition of three improved markedly, in one partially, and in three it did not improve in association with treatment. There were no apparent differences concerning clinical and neurophysiologic parameters between those whose conditions improved and those whose conditions did not.

Antibodies to myelin-associated glycoprotein are found in cerebrospinal fluid in polyneuropathy associated with monoclonal serum IgM.

Antibodies to myelin-associated glycoprotein (MAG) have been demonstrated in the serum samples from about half the patients with polyneuropathy associated with serum IgM monoclonal component. We examined cerebrospinal fluid (CSF) and serum samples from 13 patients with this disease by enzyme-linked immunosorbent assay for anti-MAG IgM antibodies. We detected these antibodies in both CSF and serum samples in 10 of the patients; in three of them the antibodies were at higher levels in the CSF. The remaining three patients had anti-MAG IgM antibodies in the CSF only. Intrathecal production of anti-MAG IgM antibodies is thus common in polyneuropathy associated with IgM monoclonal component. In three patients, examined on two occasions from 1 to 7 years, high anti-MAG IgM antibody levels persisted in CSF and serum samples. Among 165 patients with other neurologic diseases, including 60 with multiple sclerosis and 60 control subjects with tension headache, anti-MAG IgM antibodies were detected in the CSF from three patients (two with multiple sclerosis, one with aseptic meningitis), and in the serum sample of one patient with multiple sclerosis. Whether the frequent occurrence of anti-MAG IgM antibodies in CSF and their intrathecal synthesis has pathogenetic relevance for the development of polyneuropathy associated with IgM monoclonal component is unsure.

Newborn infants to myasthenic mothers: a clinical study and an investigation of acetylcholine receptor antibodies in 17 children.

We studied 17 children born to 15 myasthenic mothers; 2 of the infants had neonatal myasthenia gravis. Pyridostigmine was transferred to the child and accumulated in the amniotic fluid. Sixteen children had receptor antibodies at birth. In the affected infants, the half-life of the receptor antibody concentration was longer than it was in the others. Using an anti-idiotypic antibody, we found marked differences between the idiotypes in the mother and in affected children. Transient synthesis of receptor antibodies in the child seems to be a factor in the pathogenesis of neonatal myasthenia gravis.

No association with HLA-DR, -DQ or -DP alleles in Guillain-Barré syndrome.

The distribution of HLA class II alleles in Guillain-Barré syndrome (GBS) has previously been reported only for HLA-DR. We report here the results of genomic typing for HLA-DR, -DQ and -DP allelic variability by restriction fragment length polymorphism analysis in 49 patients with a history of GBS. No association was found to HLA-DR, -DQ or -DP alleles or HLA-DR-DQ haplotypes. Subgrouping of patients according to severity of disease, as measured by disability or muscular weakness, or response to plasmapheresis treatment, also failed to reveal significant associations. These data suggest that HLA class II genes do not confer susceptibility to GBS.

Augmented interferon-gamma, interleukin-4 and transforming growth factor-beta mRNA expression in blood mononuclear cells in myasthenia gravis.

The abnormal T lymphocyte-dependent production of antibodies to the nicotinic acetylcholine receptor (AChR) in myasthenia gravis (MG) suggests a role for immunoregulatory cytokines. We examined the T helper type 1 (Th1) cell-associated interferon-gamma (IFN-gamma) that promotes cell-mediated immunity, the Th2 cell-related interleukin-4 (IL-4) that augments B cell immunity, and transforming growth factor-beta (TGF-beta) that downregulates immune responses but enhances isotype switching. Blood mononuclear cells (MNC) expressing cytokine mRNA were enumerated after in situ hybridization with labelled complementary DNA oligonucleotide probes for IFN-gamma, IL-4 and TGF-beta. MG patients had elevated numbers of cells expressing IFN-gamma and IL-4 compared to patients with non-inflammatory neurological diseases and healthy controls, implying that both Th1- and Th2-like cells are involved in MG. TGF-beta-positive cells were also elevated in MG. The levels of cytokine-positive MNC were similar in MG and in control patients with other inflammatory neurological diseases. There were no associations between numbers of cytokine-positive blood MNC and clinical variables of MG, but individual patients need to be studied over the course of MG to clarify a relation between the cytokines under study and clinical or laboratory variables of MG.

Serum antibodies to peripheral nerve tissue in acute Guillain-Barré syndrome in relation to outcome of plasma exchange.

Mixed haemagglutination and complement fixation tests were used to detect serum antibodies to peripheral nerve in 36 patients with acute Guillain-Barré syndrome. Twenty patients were treated with plasma exchange, 16 served as controls. A significant antibody titre was found in 19 patients with the haemagglutination test; 30 had complement-fixing antibodies. Patients lacking complement-fixing antibodies were less disabled at entry (P less than 0.01). However, there was no correlation between the course of the disease and any of the antibodies in the two patient groups. The two tests were therefore not able to select patients for treatment by plasma exchange.

The clinical effect and the effect on serum IgG antibodies to peripheral nerve tissue of plasma exchange in patients wit Guillain-Barré syndrome.

The mixed haemagglutination technique was used to demonstrate IgG antibodies to peripheral nerve tissue in sera from patients with the Guillain-Barré syndrome. The clinical effect and the effect on the antibodies of plasma exchange were examined in 18 patients. Neurological examination with muscle testing and neurophysiological examination of the patients were performed before and immediately after plasma exchange. Before the exchange antibodies were detected in sera from 11 of the patients. These patients showed clinical improvement during the treatment. After plasma exchange, antibodies were detected in sera from only two of the patients. The seven patients without detectable antibodies showed no clinical improvement.

Serum carbonic anhydrase III in neuromuscular disorders and in healthy persons after a long-distance run.

A radioimmunosorbent technique was used for the assay of the skeletal muscle specific enzyme, carbonic anhydrase III (CA III). The usefulness of serum CA III determinations for detecting skeletal muscle damage was evaluated by comparing the serum levels of this enzyme and of myoglobin and creatine kinase in 64 patients with neuromuscular disorders and in 13 healthy volunteers before and after a long-distance run. Increased serum CA III levels were found in all patients with muscular dystrophy, chronic polymyositis and amyotrophic lateral sclerosis and in many with myasthenia gravis. In patients with polymyositis who were followed up with repeated blood sampling, the time courses of serum CA III levels, myoglobin levels and clinical symptoms were closely related. In all the runners the serum CA III level immediately after the run was increased. In the present study serum CA III and myoglobin seemed to be equally sensitive as biochemical markers of muscular damage and more sensitive than creatine kinase.

Serum prolactin in patients with hypothalamus and pituitary disorders.

Serum prolactin concentrations were studied in 115 patients with anatomically defined disorders in the hypothalamo-pituitary region. Fifty of the patients had expansively growing pituitary adenomas; in 17 of them (13 females and four males) the prolactin values were slightly raised (15 to 100 microgram/liter), and in 13 (11 females and two males) they were over 100 microgram/liter. The frequency of elevated prolactin values was higher for females than for males. Fifteen patients with invasively growing pituitary adenomas had very high serum prolactin levels (range 1230 to 31,500 microgram/liter). In a single case of malignant pituitary adenoma, the serum prolactin was at the lower level of detection. Of 49 further patients with suprasellar meningiomas, craniopharyngiomas, or other expansive or destructive lesions of the hypothalamus and sellar region, 15 had slightly raised prolactin values (maximum 114 microgram/liter). Eight of these 49 patients had sellar destruction, with a roentgenological picture similar to that in patients with invasive pituitary adenomas. Among these eight patients, the maximum prolactin value was 67 microgram/liter. It is concluded that moderately raised serum prolactin values (up to 100 microgram/liter) in a patient with a sellar tumor does not prove that the tumor is a prolactinoma. A serum prolactin value of 100 to 1000 microgram/liter strongly indicates a prolactin-producing tumor. In a patient with sellar destruction, a serum prolactin value of over 1000 microgram/liter is proof that the destruction is caused by an invasive pituitary adenoma.

Follow-up study of muscle function in children of mothers with myasthenia gravis during pregnancy.

Most infants whose mothers have myasthenia gravis are healthy at birth, but 10% to 15% have a transient neonatal form of myasthenia gravis. In this study, the muscular function and neuromuscular transmission were examined in 31 children, aged 3 months to 31 years (median, 10 years), of 15 myasthenic mothers. Eleven of these children had had the neonatal form of myasthenia gravis. The children were examined clinically and with neurophysiologic methods. Blood samples were taken for HLA typing, creatine kinase levels, and myoglobin and acetylcholine receptor antibody studies. Twenty-nine of the 31 children had no signs of neuromuscular disease. Two children (who had had neonatal myasthenia gravis) had a moderate stationary myopathy, probably unrelated to the myasthenia gravis of their mother. Creatine kinase levels were normal for all subjects. Acetylcholine receptor antibody levels were similar to those of a control population. The HLA type B8 antigen was not significantly more prevalent in the children who had had neonatal myasthenia gravis than in the healthy children. Neonatal myasthenia gravis in a previous sibling was the only factor in the material that predicted the occurrence of myasthenic symptoms in the neonatal period.

Plasma exchange in patients with Guillain-Barré syndrome: clinical improvement in patients with serum IgG antibodies to peripheral nerve tissue.

The mixed hemagglutination technique was used to demonstrate IgG antibodies to peripheral nerve tissue in sera from patients with Guillain-Barré syndrome. The clinical effect and the effect on the antibodies of plasma exchange (PE) were examined in 24 patients, 16 patients with acute form and 8 patients with the chronic form of the disease. Neurological examination with muscle testing and neurophysiological examination of the patients were performed before and immediately after the PE. Before PE antibodies were detected in sera from 15 of the patients. These patients showed clinical improvement during the treatment, however in one of the patients only after a time interval of 2 weeks. After PE, antibodies were detected in sera from only 3 of the patients. The 9 patients without detectable antibodies showed no clinical improvement.