Immune-mediated Polyradiculoneuropathy Research Articles

Guillain–Barré syndrome related to pandemic influenza A (H1N1) infection

Dear Editor, Since April 2009, the world has been experiencing a pandemic influenza caused by the reasserting virus A (H1N1). Little information about neurological complications induced by this virus is available in the literature. We report the case of a 37-year-old woman who was admitted to our intensive care unit for respiratory distress associated with flaccid tetraplegia. Two weeks ago, she had fever, asthenia, and cough. A nasopharyngeal swab was performed, and reverse-transcription polymerase chain reaction (RT-PCR) confirmed infection with pandemic flu virus A (H1N1). Ten days later, she suffered muscular weakness of the lower limb, then the upper limb. At admission, she had normal consciousness, flaccid tetraplegia with complete areflexia, and symmetric paresthesia of the lower limb. A few hours later, she developed severe dyspnea with impaired coughing, accumulation of airway secretions, nasal voice, swallowing difficulties, and severe hypoxemia (SpO2 at 85% under 10 l oxygen/min) requiring mechanical ventilation. During the first 2 days, episodes of bradycardia and hypertension were recorded on hemodynamic monitoring. Diagnosis of Guillain–Barre syndrome was considered and confirmed by electromyography showing reduction in motor conduction velocity and prolonged distal latencies, which were more severe in the lower limb. On analysis of cerebrospinal fluid, there was no albuminocytologic dissociation. Investigations performed in order to identify another triggering factor were negative. Five consecutive plasma exchanges were performed, and the patient improved progressively. Repeated and prolonged weaning tests were successful, and the patient had a vigorous cough. She was free from mechanical ventilation within 2 weeks, and neither swallowing problems nor dysautonomia abnormalities were reported. The patient was discharged from our intensive care unit within 45 days. Guillain–Barre syndrome is an acute, immune-mediated polyradiculoneuropathy. In 66% of patients, history of respiratory or gastrointestinal infection within 6 weeks preceding onset of the disease is found [1]. Some infectious agents are particularly known as triggering factors of Guillain–Barre syndrome [2]. Sivadon-Tardy et al. [3] reported that influenza virus can also induce Guillain–Barre syndrome, but the majority of infections were due to virus A (H3N2), and clinical course was less severe compared with other infectious agents. For our patient, acute respiratory failure and bulbar dysfunction were the main causes leading to intensive care admission. Bulbar dysfunction can be responsible for autonomic instability and aspiration that worsens respiratory distress [4]. Determining the best time for mechanical ventilation is crucial, and up to 25% of patients with Guillain–Barre syndrome may need mechanical ventilation [1]. Delayed intubation, especially when bulbar dysfunction is considered, may increase the risk of early-onset pneumonia related to aspiration [4]. In adults, plasmapheresis is considered the gold standard for treatment of the most severe cases of Guillain– Barre syndrome. In five randomized trials, plasma exchange reduced the need for prolonged ventilation from 27% to 4% [2]. To the best of our knowledge, there are no available data concerning clinical severity and prognosis of Guillain–Barre syndrome related to pandemic flu virus A (H1N1). Further studies are needed to clarify the incidence of this complication and its prognostic impact.

Epidemiologic Investigation of Immune-Mediated Polyradiculoneuropathy among Abattoir Workers Exposed to Porcine Brain

BackgroundIn October 2007, a cluster of patients experiencing a novel polyradiculoneuropathy was identified at a pork abattoir (Plant A). Patients worked in the primary carcass processing area (warm room); the majority processed severed heads (head-table). An investigation was initiated to determine risk factors for illness.Methods and ResultsSymptoms of the reported patients were unlike previously described occupational associated illnesses. A case-control study was conducted at Plant A. A case was defined as evidence of symptoms of peripheral neuropathy and compatible electrodiagnostic testing in a pork abattoir worker. Two control groups were used - randomly selected non-ill warm-room workers (n = 49), and all non-ill head-table workers (n = 56). Consenting cases and controls were interviewed and blood and throat swabs were collected. The 26 largest U.S. pork abattoirs were surveyed to identify additional cases. Fifteen cases were identified at Plant A; illness onsets occurred during May 2004–November 2007. Median age was 32 years (range, 21–55 years). Cases were more likely than warm-room controls to have ever worked at the head-table (adjusted odds ratio [AOR], 6.6; 95% confidence interval [CI], 1.6–26.7), removed brains or removed muscle from the backs of heads (AOR, 10.3; 95% CI, 1.5–68.5), and worked within 0–10 feet of the brain removal operation (AOR, 9.9; 95% CI, 1.2–80.0). Associations remained when comparing head-table cases and head-table controls. Workers removed brains by using compressed air that liquefied brain and generated aerosolized droplets, exposing themselves and nearby workers. Eight additional cases were identified in the only two other abattoirs using this technique. The three abattoirs that used this technique have stopped brain removal, and no new cases have been reported after 24 months of follow up. Cases compared to controls had higher median interferon-gamma (IFNγ) levels (21.7 pg/ml; vs 14.8 pg/ml, P<0.001).DiscussionThis novel polyradiculoneuropathy was associated with removing porcine brains with compressed air. An autoimmune mechanism is supported by higher levels of IFNγ in cases than in controls consistent with other immune mediated illnesses occurring in association with neural tissue exposure. Abattoirs should not use compressed air to remove brains and should avoid procedures that aerosolize CNS tissue. This outbreak highlights the potential for respiratory or mucosal exposure to cause an immune-mediated illness in an occupational setting.

Pharmacokinetics of Intravenous Immunoglobulin in Guillain-Barré Syndrome

Guillain-Barre syndrome (GBS), an immune-mediated inflammatory polyradiculoneuropathy, is the most common cause of rapidly progressive generalized

Axonal variant of Guillain-Barré syndrome associated with Campylobacter infection in Bangladesh

Campylobacter jejuni enteritis is the predominant bacterial infection preceding Guillain-Barré syndrome (GBS), an acute postinfectious immune-mediated polyradiculoneuropathy. The purpose of this study was to define the clinical phenotype of GBS and the relation with preceding C jejuni infections in Bangladesh. We performed a prospective matched case-control hospital surveillance including 100 patients fulfilling the National Institute of Neurological Disorders and Stroke criteria for GBS from 2006 to 2007 in the Dhaka area of Bangladesh. Detailed clinical, electrophysiologic, serologic, and microbiologic data were obtained with a follow-up of 6 months. GBS affected predominantly young adult males living in rural areas. Sixty-nine percent of the patients had clinical evidence of a preceding infection. The most frequent symptom was diarrhea (36%). The majority of patients had a pure motor variant of GBS (92%) with relatively infrequent cranial nerve involvement (30%). Twenty-five percent of patients required respiratory support. Electrophysiologic studies showed that 67% of patients had an axonal variant of GBS. Eleven patients (14%) died, and 23 (29%) remained severely disabled during the follow-up. Positive C jejuni serology was found in an unprecedented high frequency of 57% as compared with 8% in family controls and 3% in control patients with other neurologic diseases (p < 0.001). C jejuni infection was significantly associated with serum antibodies to the gangliosides GM1 and GD1a, axonal neuropathy, and greater disability. We report an unusually high frequency of the axonal variant of Guillain-Barré syndrome in Bangladesh, associated with preceding Campylobacter jejuni infection, severe residual disability, and high mortality.

A Clustering of Immune-mediated Polyradiculoneuropathy among Swine Abattoir Workers Exposed to Aerosolized Porcine Brains, Indiana, United States

In November 2007 a novel neuropathy, immune-mediated polyradiculoneuropathy (IP), was identified among workers at a Minnesota swine abattoir where a unique compressed air technique was used to remove porcine brains. An epidemiologic investigation at another abattoir in Indiana that also uses this process was launched to evaluate workers self-reporting neurologic illness compatible with IP. A nested case-control study was performed to identify cases and risk factors. Six confirmed, one probable, and three possible IP cases were detected. IP cases were 28-52 years old, of Latino origin, and 62.5% female. Onset dates ranged from April 2005-December 2007; 60% were hospitalized. IP cases at this plant were similar in clinical presentation and exposure risks to those detected in Minnesota. Swine abattoirs using similar brain extraction methods should discontinue this process.

A Clustering of Immune-mediated Polyradiculoneuropathy among Swine Abattoir Workers Exposed to Aerosolized Porcine Brains, Indiana, United States

A Clustering of Immune-mediated Polyradiculoneuropathy among Swine Abattoir Workers Exposed to Aerosolized Porcine Brains, Indiana, United States

Antiganglioside antibodies and their pathophysiological effects on Guillain-Barre syndrome and related disorders--A review

Guillain-Barré syndrome (GBS) is an acute immune-mediated polyradiculoneuropathy which can cause acute quadriplegia. Infection with micro-organisms, including Campylobacter jejuni (C. jejuni), Haemophilus influenzae, and Cytomegalovirus (CMV), is recognized as a main triggering event for the disease. Lipooligosaccharide (LOS) genes are responsible for the formation of human ganglioside-like LOS structures in infectious micro-organisms that can induce GBS. Molecular mimicry of LOSs on the surface of infectious agents and of ganglioside antigens on neural cells is thought to induce cross-reactive humoral and cellular immune responses. Patients with GBS develop antibodies against those gangliosides, resulting in autoimmune targeting of peripheral nerve sites, leading to neural damage. Heterogeneity of ganglioside expression in the peripheral nervous system (PNS) may underlie the differential clinical manifestation of the GBS variants. Recent studies demonstrate that some GBS sera react with ganglioside complexes consisting of two different gangliosides, such as GD1a and GD1b, or GM1 and GD1a, but not with each constituent ganglioside alone. The discovery of antiganglioside complex antibodies not only improves the detection rate of autoantibodies in GBS, but also provides a new concept in the antibody-antigen interaction through clustered carbohydrate epitopes. Although ganglioside mimicry is one of the possible etiological causes of GBS, unidentified factors may also contribute to the pathogenesis of GBS. While GBS is not considered a genetic disease, host factors, particularly human lymphocyte antigen type, appear to have a role in the pathogenesis of GBS following C. jejuni infection.

Polyethylene Glycol Interferon .ALPHA.-2b-induced Immune-mediated Polyradiculoneuropathy

Polyethylene glycol-interferon alpha (PEG-IFNalpha) has been used as the standard treatment for hepatitis C virus (HCV) infection. There have been no previous reports of polyradiculoneuropathy with anti-ganglioside antibodies induced by PEG-IFNalpha-2b. We report a 59-year-old man who developed polyradiculoneuropathy during treatment with PEG-IFN alpha-2b for chronic HCV infection. Serum levels of anti-asialo-GM1 (GA1) and anti-GM1 antibodies were elevated. Cessation of therapy with double filtration plasmapheresis resulted in marked improvement in his symptoms accompanied by a reduction in the antibody level. PEG-IFN alpha-2b may induce peripheral neuropathy mediated by anti-GA1 and anti-GM1 antibodies.

Intravenous Immunoglobulin Treatment Successfully Improved Subacute Progressive Polyradiculoneuropathy with Polyclonal Gammopathy

The present case was an elderly man with a history of gastric cancer, diffuse biliary duct stenosis and liver cirrhosis. He had markedly elevated IgG, suggesting chronic infection or inflammatory changes in the biliary duct. He developed weakness in his arms and became unable to use his hands within one month and 2 weeks later, he had difficulty walking. Based on his progressive disease course, elevated serum IgG, nerve conduction study and enhanced MRI findings, we diagnosed him as suffering from immune-mediated subacute polyradiculoneuropathy with polyclonal gammopathy, which might be related to Guillain-Barré syndrome. Intravenous immunoglobulin (IVIg) was dramatically effective in this patient. In the follow-up 6 months later he was stable and could walk without a cane. Even in patients with polyclonal gammopathy in chronic inflammatory disease of another organ, IVIg may be effective and beneficial for the patients's quality of life.

Tumor necrosis factor‐α‐converting enzyme is expressed in the inflamed peripheral nervous system

Tumor necrosis factor-alpha (TNF-alpha) is considered to play a critical role in the pathogenesis of immune-mediated inflammatory demyelinating disorders of the peripheral nervous system (PNS). Processing of membrane-bound inactive pro-TNF-alpha into the active soluble cytokine is mediated by a sheddase, the so-called TNF-alpha-converting enzyme (TACE), a member of the A Disintegrin and Metalloproteinase (ADAM) family. We explored the expression of TACE (ADAM-17) in sciatic nerves from Lewis rats with experimental autoimmune neuritis (EAN), an animal model of the Guillain-Barré syndrome (GBS), an immune-mediated polyradiculoneuropathy. To extend our study to human disease, sural nerve biopsies from GBS patients were investigated by immunohistochemistry. In EAN, T lymphocytes could be defined as the cellular source of ADAM-17 with peak expression levels at maximum clinical disease severity. Similarly, in human sural nerves, ADAM-17-expressing T cells could be localized primarily within the epi- and perineurium, whereas in control sections from patients with non-inflammatory neuropathies, no expression could be depicted. Our findings indicate that ADAM-17 is upregulated during EAN and expressed in nerves of GBS patients and thus may contribute to the pathogenesis of inflammatory demyelination of the PNS.