Inflammatory Polyneuropathy Research Articles

Encephalomyeloneuritis simulating Guillain-Barré syndrome.

A patient with encephalomyeloneuritis (EMN) had clinical and laboratory features consistent with severe acute inflammatory polyneuropathy (Guillain-Barré syndrome). CNS involvement was suggested clinically only by transient downbeat nystagmus and by contraction of tensor fascia lata on plantar stimulation. Postmortem examination revealed pathologic changes typical of EMN without systemic neoplasm. Clinical manifestations of the profound central pathology were largely obscured by severe radiculoneuropathy. Pathologic verification of clinically diagnosed inflammatory polyneuropathy is unusual, and CNS disease, therefore, may be more frequent than appreciated, especially in clinical "variants."

Neurological manifestations of the acquired immunodeficiency syndrome (AIDS): experience at UCSF and review of the literature.

In this review of the acquired immunodeficiency syndrome (AIDS), the authors have evaluated a total of 352 homosexual patients with AIDS or generalized lymphadenopathy managed at the University of California, San Francisco (UCSF), between 1979 and 1984. Of an initial unselected group of 318 patients, 124 (39%) were neurologically symptomatic, and one-third already had their neurological complaints at the time of presentation. An additional 210 AIDS patients with neurological symptoms have been reported in the literature. Thus, a total of 366 neurologically symptomatic patients with AIDS or lymphadenopathy are reviewed. Central nervous system (CNS) complications, encountered in 315 patients, included the following viral syndromes: subacute encephalitis (54), atypical aseptic meningitis (21), herpes simplex encephalitis (nine), progressive multifocal leukoencephalopathy (six), viral myelitis (three), and varicella-zoster encephalitis (one). Non-viral infections were caused by Toxoplasma gondii (103), Cryptococcus neoformans (41), Candida albicans (six), Mycobacteria (six), Treponema pallidum (two), coccidioidomycosis (one), Mycobacterium tuberculosis (one), Aspergillus fumigatus (one), and Escherichia coli (one). Neoplasms included primary CNS lymphoma (15), systemic lymphoma with CNS involvement (12), and metastatic Kaposi's sarcoma (three). Cerebrovascular complications were seen in four patients with hemorrhage and five with infarction. Five patients in the UCSF series had multiple intracranial pathologies, including two cases of simultaneous Toxoplasma gondii infections and primary CNS lymphoma, two cases of coexistent Toxoplasma gondii and viral infections, and one case of combined Toxoplasma gondii and atypical mycobacterial infection. Cranial or peripheral nerve complications, seen in 51 patients, included cranial nerve syndromes secondary to chronic inflammatory polyneuropathy (five), lymphoma (five), and Bell's palsy (five). Peripheral nerve syndromes included chronic inflammatory polyneuropathy (12), distal symmetrical neuropathy (13), herpes zoster radiculitis (six), persistent myalgias (two), myopathy (two), and polymyositis (one). In light of the protean behavior of AIDS and the problems related to the clinical, radiological, and serological diagnosis of the unusual and varied associated nervous system diseases, patients with AIDS and neurological complaints require a rigorous and detailed evaluation. The authors' experience suggests that biopsy of all CNS space-occupying lesions should be performed for tissue diagnosis prior to the institution of other therapies.

Quantitative Surface Electromyography for Monitoring Patients with Inflammatory Polyneuropathy

Quantitative Surface Electromyography for Monitoring Patients with Inflammatory Polyneuropathy

Effects of glucocorticoids on experimental allergic neuritis

Corticosteroids were administered to rats and guinea pigs with experimental allergic neuritis, from the time of inoculation with antigen or from the onset of signs of disease. No statistically significant effects were observed in guinea pigs. In rats, to which large doses of corticosteroids were administered, disease severity was slightly but significantly reduced in both groups and recovery was more rapid in the animals treated from the time of induction of disease. These results were comparable with those obtained in trials of corticosteroids in acute inflammatory polyneuropathy in man, which have also not demonstrated any striking effects.

Chronic inflammatory polyneuropathy: Reduction of nerve conduction velocities in monkeys by systemic passive transfer of immunoglobulin G

In chronic (relapsing) inflammatory polyneuropathy (CRIP), successful treatment with plasma exchange has led to the concept of pathogenic humoral factors. In 6 patients with CRIP, 5 of whom improved after plasma exchange, the potential pathogenic role of circulating immunoglobulin (Ig) fractions was tested by applying the systemic passive transfer model to marmoset monkeys. After continuous treatment with intramuscular injections for 2–8 weeks, monkeys injected with the crude immunoglobulin fractions or with purified IgG from 5 of the 6 patients showed a significant and partially reversible reduction of the motor nerve conduction velocity (mean 34%, P < 0.001) when compared with pre-treatment values. In control animals the reduction was 4%. Morphological examination revealed only minor ultrastructural changes of the myelin sheath. Immunocytochemistry revealed that human IgG was able to cross the blood-nerve barrier. It is concluded that the circulating IgG-fraction of patients with CRIP contains a factor that may contribute to the disordered nerve function after crossing the blood-nerve barrier. It may be the removal of this particular factor which is responsible for the rapid recovery of nerve conduction in patients after plasma exchange.

Disorders of Peripheral Nerves

Disorders of the peripheral nerves are one of the most difficult and often frustrating parts of neurology. This is amply shown by the amount of new research on diseases of the peripheral nervous system in the past ten years. This complex, and what might be considered tedious subject, has been brought into clear focus by Schaumburg, Spencer, and Thomas in the latest addition to the<i>Contemporary Neurology</i>Series library. Using a terse style, these authors have managed to reduce an overwhelming amount of material to a manageable form. The first two of 20 chapters present an up-to-date review of basic concepts and the new terminology and anatomic classification of disorders of peripheral nerves. Clear diagrams and charts aid the reader's understanding of recent developments. Following a concise review of the Gullain-Barré syndrome and related disorders (the inflammatory polyneuropathies) are six chapters devoted to the metabolic and nutritional neuropathies. An important

The “Bodelye syeknes” of Julian of Norwich

In 1373 Julian of Norwich fell ill and experienced a series of visions which she later described in writings well known to students of English mysticism. Her account of the illness, though relatively rich in detail, has received little systematic attention. This paper examines the passages in Julian's writings which bear on her sickness and attempts to identify diseases known today which answer to her description. The central feature of her compliants was a paralysis which began in her legs and ascended to her trunk, arms and neck. Four disorders causing ascending paralysis are advanced as leading candidates for the diagnosis: diphtheria, inflammatory polyneuropathy, tick paralysis and botulism. Of the four, it is argued, botulism seems the most likely to have been responsible for Julian's illness.

The treatment of experimental allergic neuritis by plasma exchange

Experimental allergic neuritis (EAN) is a demyelinating disease of the peripheral nervous system that can be induced in laboratory animals. This disorder has been considered to show many similarities to acute inflammatory polyneuropathy (Guillain-Barré syndrome, GBS). Reports that plasma exchange may benefit patients with GBS prompted the investigation of the effect of plasma exchange in EAN. A controlled study was performed on New Zealand White rabbits. Sixteen animals were allocated to control or treatment groups at the onset of the disease. Clinical assessment on days 7 and 14 showed that treated animals were less severely affected neurologically ( P = 0.05, day 7; P < 0.001 day 14), with a commensurate reduction in the severity of the histological lesions in peripheral nerves.

Immune reactions to P2 protein in human inflammatory demyelinative neuropathies.

The significance of immune reactions against peripheral nervous system antigens in the human inflammatory polyneuropathies is still uncertain. Using a very sensitive assay, we found greatly increased levels of anti-P2 antibodies in sera of animals with experimental allergic neuritis (EAN) but no increases in humans with acute Guillain-Barré syndrome (GBS), chronic relapsing polyneuritis (CRIP), axonal neuropathy, or normals. P2 protein and CNS basic protein did not induce any increased proliferation in lymphocytes of GBS or CRIP patients. We conclude that P2 and BP appear unlikely to be targets for humoral or cellular immune reactivity in GBS or CRIP.

Chronic idiopathic polyneuropathy treated with azathioprine.

The results of azathioprine therapy in five patients with chronic progressive or relapsing idiopathic inflammatory polyneuropathy are described. In four patients a sustained improvement followed treatment and in the other patient azathioprine successfully replaced corticosteroid therapy. The improvement was often delayed for up to three months. The literature on the use of azathioprine in chronic polyneuropathy is reviewed. We suggest that there is a place for azathioprine treatment in patients with chronic idiopathic polyneuropathy resistant or intolerant to corticosteroid treatment.

Neuroimmunology I: Immunoregulation in neurological disease.

Aberrations in immune function that ultimately result in disease states may involve three aspects of immune regulation: (1) regulatory T cells, which both suppress and induce immune responses; (2) idiotype-antiidiotype networks, which serve as internal regulatory networks during generation of an immune response; and (3) immune response genes, which determine genetic differences in an individual's immune response. Three major diseases of the nervous system, multiple sclerosis, myasthenia gravis, and acute inflammatory polyneuropathy (Guillain-Barré syndrome), are classified as "autoimmune" in nature and may be due to underlying disorders of immunoregulation. In multiple sclerosis there is a loss of suppressor T cells in the peripheral blood during attacks, in myasthenia gravis there are thymic abnormalities and antibodies against the acetylcholine receptor, and in acute inflammatory polyneuropathy, macrophage-mediated destruction of peripheral nerve myelin occurs in the context of sensitized T cells and is usually associated with a preceding viral illness. In each of these diseases the following central questions must be answered: (1) against what antigen (or antigens) of the nervous system is the autoimmune response directed? (2) what is the mechanism of immune damage? and (3) what initiates, or triggers, the autoimmune response?

Chronic relapsing polyneuropathy associated with immunoblastic lymphadenopathy

Two episodes of severe, relapsing sensorimotor polyneuropathy closely paralleled the course of systemic illness in a patient with immunoblastic lymphadenopathy. A review of the literature shows three other cases, although none with documented pathologic changes in muscles and nerves. Based on the pathologic findings in this patient, the peripheral neuropathy associated with immunoblastic lymphadenopathy can be classified under the group of relapsing inflammatory polyneuropathies associated with systemic disorders. Whether prednisone therapy helped this condition is uncertain.

Complement-fixing antiperipheral nerve myelin antibodies in patients with inflammatory polyneuritis and with polyneuropathy and paraproteinemia.

Serum from patients with peripheral neuropathies was tested for antiperipheral nerve myelin antibodies by complement fixation. Antibody activity was detected in 5 of 20 patients with acute or chronic remitting polyneuritis and in 4 of 20 patients with polyneuropathy and paraproteinemia but not in patients with other types of neuropathy, neurologic disease, or immunologic disease. In three patients with IgM paraproteinemia, the complement-fixing activity resided in the IgM fraction; in one patient with chronic inflammatory polyneuritis, antibody activity resided in the IgG fraction. In the inflammatory polyneuropathies, antibody titers did not always correlate with disease activity. Sera from patients with remitting polyneuropathies reacted with either human or rabbit peripheral nerve myelin, but sera from patients with paraproteinemia reacted only with human myelin.

The treatment of chronic relapsing and chronic progressive idiopathic inflammatory polyneuropathy by plasma exchange

Observations are reported on the effects of plasma exchange on three patients with chronic relapsing idiopathic inflammatory polyneuropathy and three with the chronic progressive form of this disorder. Substantial temporary improvement occurred in two of the chronic relapsing cases in relation to repeated plasma exchanges, but only slight improvement in the remainder. A striking feature was the rapidity of the effect in the patients that improved. The significance of these observations in relation to pathogenesis and to clinical management of the disorder is discussed.

Treatment of acute inflammatory polyneuropathy.

Most patients with acute inflammatory polyneuropathy (AIP) recover spontaneously, but the time course of the illness is unpredictable so that the results of treatment are difficult to assess. Three decades of retrospective reports of steroid treatment fail to demonstrate any striking beneficial effect. In a randomized trial of prednisolone, starting dose 60 mg daily, 21 treated patients improved more slowly than 19 untreated patients. By contrast, in rats immunized with bovine nerve root myelin, prednisolone at 10 mg/kg reduced the severity and duration of experimental allergic neuritis (EAN), the putative animal model for AIP. This discrepancy might reflect the greater difficulty of clinical as opposed to animal therapeutic trials or indicate that EAN is not the appropriate model for the human disease. Immunosuppressive drugs, plasmapheresis and other agents have also been employed, but their efficacy cannot be decided from the available case report. The role of similar agents in chronic progressive and relapsing inflammatory neuropathy cannot yet be resolved, but in some patients steroids do appear to be valuable.

HLA antigens in chronic relapsing idiopathic inflammatory polyneuropathy

Observations are reported on 14 patients with a clinical diagnosis of recurrent or chronic relapsing idiopathic inflammatory polyneuropathy of Guillain-Barré type. The results suggest the possibility of a disease susceptibility gene for this disorder associated with the HLA-A1, -B8, -DRw3, and -Dw3 haplotype.

Identification of the neuritogen for experimental allergic neuritis

EXPERIMENTAL ALLERGIC NEURITIS (EAN) is a model of human acute inflammatory polyneuropathy, Guillain–Barre syndrome. It can be produced in several species of laboratory animal by immunisation with homologous or heterologous peripheral nerve emulsified in Freund's complete adjuvant1,2. After about two weeks the animals may develop signs varying from ataxia to paralysis and death. EAN has been produced using crude acid extracts of peripheral nerve3,4, but investigations into the neuritogenic properties of the component proteins of peripheral nerve myelin have yielded inconclusive results5–10. In experimental allergic encephalomyelitis (EAE), the central nervous system (CNS) counterpart of EAN, the encephalitogenic antigen has been shown to be a CNS myelin basic protein of molecular weight 18,000 (ref. 11). The three major proteins of peripheral nerve myelin, which together account for about 75% of the myelin protein, are usually referred to as P0, P1 and P2 (ref. 12). P0 is a glycoprotein of molecular weight 30,000 and P1 and P2 are both basic proteins with molecular weights of 18,000 and 12,000–14,000, respectively12–13. We describe here a reliable method for producing severe EAN in inbred Lewis rats with bovine intradural root material, and show that intact P2, the major basic protein of peripheral nerve myelin, is the responsible neuritogen.