Primary cytomegalovirus infection in patients with Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) is frequently associated with the presence of CMV-specific IgM-antibodies or CMV-DNA in serum. Detection of IgM-antibodies or viremia may indicate primary infection, but also reactivation or reinfection. We identified 46 GBS patients with detectable CMV-specific IgM- or IgG-antibodies, or both. Sera from these patients were tested for the presence of CMV-specific, low-avidity IgG-antibodies, which indicate primary infection that occurred <6 months before sample collection, and for the presence of CMV-DNA by polymerase chain reaction (PCR). Primary infection was identified by the presence of low-avidity IgG-antibodies in 9/46 (20%) or by detection of IgM-antibodies in the absence of IgG-antibodies in 1/46 (2%) patients. CMV-DNA was detectable in 17/46 (37%) sera. In contrast, CMV-DNA was detected in only 2% of sera from 46 age-matched patients with neuroborreliosis. The likelihood of viremia decreased in GBS patients significantly with increasing antibody-avidity (P=0.041). Detection of IgM-antibodies correlated with that of CMV-DNA in patients with low-avidity IgG-antibodies (P=0.048) but not in those with high-avidity IgG-antibodies (P=0.543). In 45 age-matched healthy controls, low-avidity IgG-antibodies and CMV-DNA were detected in only 2% and 0% of sera, respectively. Our findings further strengthen evidence for an association between CMV infection and GBS. Primary CMV infection was identified in almost one-fourth of patients with detectable CMV-specific antibodies. Nevertheless, endogenous reactivation and reinfection have to be considered also as relevant events associated with GBS.     

Factors predicting extubation success in patients with Guillain-Barré syndrome

Introduction  

Accurate prediction of successful extubation in patients with Guillain-Barré syndrome (GBS) is an important clinical problem. We hypothesized that reversal of clinical indices used to intubate a patient (i.e., declining vital capacity [VC]) predict extubation.     

Interleukin-10 promoter polymorphisms in patients with Guillain-Barré syndrome

Interleukin-10 (IL-10) may have both pro- and anti-inflammatory effects in Guillain-Barré syndrome (GBS). The distribution of polymorphisms in the IL-10 gene (-1082 (G/A), -819 (T/C) and -592 (A/C)) was analysed to determine whether they could influence disease susceptibility or clinical course in GBS. The -592 CC and -819 CC genotypes associated with increased IL-10 response were more frequent in the GBS patients than in the controls (P=0.027), but the polymorphisms did not influence the clinical course of the disease.     

Supportive care for patients with Guillain-Barré syndrome

A multidisciplinary consensus group searched MEDLINE from 1966 to May 2003, extracted relevant references, and prepared recommendations on supportive care for Guillain-Barré syndrome. In the absence of randomized controlled trials, we agreed on recommendations by consensus based on observational studies and expert opinion. In the acute phase in bed-bound adult patients, the group recommended the use of heparin and graduated pressure stockings to prevent deep vein thrombosis, monitoring for blood pressure, pulse, autonomic disturbances, and respiratory failure, and the timely institution of artificial ventilation and tracheostomy. Pain management is difficult, but carbamazepine or gabapentin may help. The cautious use of narcotic analgesics may be needed. Disabled patients should be treated by a multidisciplinary rehabilitation team and should receive an assistive exercise program. Persistent fatigue following Guillain-Barré syndrome is common and may be helped by an exercise program. Because of a very small and possibly only theoretical increase in the risk of recurrence following immunization, the need for immunization should be reviewed on an individual basis. More research is needed to identify optimal methods for all aspects of supportive care.     

Long-term outcome in patients with Guillain-Barré syndrome requiring mechanical ventilation

OBJECTIVE: To analyze long-term recovery and predictors of outcome in patients with Guillain-Barré syndrome (GBS) requiring mechanical ventilation. METHODS: The clinical and electrophysiologic data of 114 patients with GBS admitted to the intensive care unit between 1976 and 1996 (60 mechanically ventilated, 54 nonventilated) were reviewed. Functional disability and predictors of outcome were determined at 1 year and at maximal recovery using the Hughes scale. Good outcome was defined as ability to ambulate without assistance; poor outcome was defined as inability to ambulate independently. RESULTS: Mechanical ventilation was required in 81% of patients with a poor outcome. Mortality was 20% in patients ventilated for GBS. However, ventilated patients who survived did well, with 79% eventually regaining independent ambulation. Nineteen percent of patients improved at least one functional grade beyond 1 year. Univariate predictors of poor maximal recovery in ventilated GBS patients were increased age (p < 0.001)), upper limb paralysis (p = 0.004), duration of ventilation (p = 0.006), and delay of more than 2 days to transfer to a tertiary center (p < 0.001). However, only age (OR 1.99, p = 0.004) and delayed transfer (OR 19.8, p = 0.002) were independently predictive of poor outcome on multivariate analysis. CONCLUSION: Mechanically ventilated patients constitute the majority of GBS patients with a poor outcome, and mortality remains substantial in this subgroup (20%). Although recovery from severe GBS may be prolonged, most survivors regain independent ambulation.     

Lymphocyte subset proportions in Guillain-Barré syndrome patients treated with plasmapheresis

We examined the changes in the proportions of certain T cell subsets in 18 Guillain-Barré syndrome patients treated with plasmapheresis (PP). PP was performed within 8 days after the onset using a continuous-flow blood cell separator or immunoadsorption. The proportions of CD3+, CD4+ and CD4+CD45RA+ cells at the onset were decreased and that of CD19+ was increased compared with those of 25 normal controls. However, the proportions of CD4+CD45R-, CD4+HLADR+, CD4+CD25+ cells and the CD8+ subpopulations were similar in patients and controls. After PP, the altered subsets tended to normalize, particularly in the group that improved after PP.     

Relationship between clinical activity and lymphocyte subsets in patients with Guillain-Barré syndrome]

T lymphocytes are probably of pathogenic importance in Guillain-Barré syndrome (GBS). Blood samples from 31 patients with GBS and from 25 healthy controls were studied with flow cytometry. Subsets of the CD4 population were determined: CD4+CD29+ (helper-inducer) cells and CD4+CD45RA+ (naive or suppressor-inducer) cells. Recently, deviations of circulating CD8 populations have been noticed. Therefore, subsets of the CD8 population were also determined: CD8+CD11b dull (suppressor-effector) cells and CD8+ CD11b bright (cytotoxic-effector/NK) cells. During the active stage of GBS, significantly increased proportions of CD4+HLA-DR+ (activated CD4+) cells and CD4+CD29+ cells were found compared to those in control samples (p < 0.0005, p < 0.05, respectively). The proportion of CD8+CD11b dull cells was significantly lower than that in the control samples (p < 0.005). Sequential analysis showed a decrease in the proportion of CD4+HLA-DR+ cells and CD4+CD29+ cells from the active to the convalescent stage (p < 0.05, p < 0.005, respectively). The proportion of CD8+CD11b dull cells was low in GBS patients with high disease severity.     

Changes in referral pattern and its effect on outcome in patients with Guillain-Barré syndrome

The authors assessed the referral pattern and outcome in patients with Guillain-Barré syndrome (n = 266) after the introduction of intravenous immunoglobulin (IVIg). Fewer patients were transferred from small to large hospitals after the introduction of IVIg (p = 0.05). This did not result in a worse outcome in patients treated in small centers. The introduction of IVIg has led to a better use of different levels of health care facilities.     

Risk of cancer in patients with Guillain-Barré syndrome (GBS)

Abstract. The possible relationship between Guillain-Barré syndrome (GBS) and cancer is still controversial and the existence of a paraneoplastic GBS remains unconfirmed. To better define whether there is a relationship between GBS and malignancy, we compared the observed and the expected number of patients with tumours in a population-based cohort of subjects with GBS. Clinical differences between GBS patients with or without malignancies were analysed. Data were obtained from the Piemonte and Valle dAosta Register for GBS (PARGBS) (years 1990–1998). GBS was diagnosed according to NINCDS criteria. The number of expected cases of malignancy in the PARGBS population was calculated using the incidence rate of all types of cancer (ICD codes 140–208) in Piemonte [1985–1987], and in the most important town of this region, that is Turin (years 1993–1997). In the nine-year period, 435 incident patients with GBS were found. Nine of them developed cancer in the six months preceding or following GBS; in seven of them, the diagnosis of cancer and GBS was concomitant. The expected number of malignant tumours was 3.7 (using the incidence in Piemonte) and 3.8 (using the incidence in Turin); therefore, the odds ratios were 2.43 (95 % CI, 1.11–4.62) and 2.37 (95% CI, 1.09–4.50), respectively (p < 0.01). Although the cases with malignancies were clinically similar to the other cases of GBS observed through the Register, the mortality in GBS patients with cancer was higher and was the final cause of death in two patients affected by severe cancer. These results suggest a possible correlation between some cases of GBS and cancer. However, GBS in cancer patients does not meet all the criteria for paraneoplastic diseases.* Piemonte and Valle dAosta Register for GBS (PARGBS): Coordinating center: 2^nd Division of Neurology, Department of Neuroscience, University of Torino, Italy. Project coordinator: A. Chiò, MD. Study monitors: A. Calvo, MD, N. Di Vito, MD, M. Vercellino, MD. Scientific Committee: A. Bertolotto, MD, E. Bottacchi, MD, A. Chiò, MD, D. Cocito, MD, M. T. Giordana, MD, M. Leone, MD, L. Mazzini, MD, G. Mora, MD. Collaborating centers: A. Chiò, MD, A. A. Terreni, MD, D. Schiffer, MD, R. Mutani, MD, D. Cocito, MD, B. Bergamasco, MD, I. Rainero, MD (Department of Neuroscience, Section of Neurology, University of Torino, and Azienda Ospedaliera San Giovanni Battista, Torino), A. Bertolotto, MD, A. Tribolo, MD, R. Sciolla, MD, F. Mondino, MD, M. T. Giordana, MD (Department of Neuroscience, Section of Neurology, University of Torino, and Azienda Ospedaliera San Luigi Gonzaga, Orbassano), M. Leone, MD, P. Gaviani, MD, F. Monaco, MD (Department of Neurology, Amedeo Avogadro University, Novara), M. De Mattei, MD, E. Morgando, MD (Department of Neurology, Azienda Ospedaliera San Giovanni, Torino), L. Sosso, MD, M. Gionco, MD (Department of Neurology, Ospedale Mauriziano, Torino), U. Morino, MD, M. Nobili, MD (Department of Neurology, Ospedale Martini, Torino), L. Appendino, MD (Department of Neurology, Ospedale Maria Vittoria, Torino), D. Piazza, MD (Department of Neurology, Ospedale S. Giovanni Bosco, Torino), E. Oddenino, MD, W. Liboni, MD (Department of Neurology, Ospedale Gradenigo, Torino), G. Vaula, MD, G. Ferrari, MD (Department of Neurology, Ivrea), M. Favero, MD, C. Doriguzzi Bozzo, MD (Department of Neurology, Pinerolo), P. Santamaria, MD (Department of Neurology, Vercelli), U. Massazza, MD, E. Bollani, MD (Department of Neurology, Biella), A. Villani, MD, R. Conti, MD (Department of Neurology, Domodossola), G. Mora, MD, C. Balzarini, MD (Department of Neurological Rehabilitation, Fondazione S. Maugeri, Clinica del Lavoro e della Riabilitazione, IRCCS, Scientific Institute of Veruno), M. Palermo, MD (Department of Neurology, Alessandria), F. Vergnano, MD (Department of Neurology, Casale Monferrato), S. Cordera, MD, C. Buffa, MD (Department of Neurology, Novi Ligure), M. T. Penza, MD (Department of Neurology, Tortona), F. Fassio, MD (Department of Neurology, Asti), P. Meineri, MD (Department of Neurology, Azienda Ospedaliera Santa Croce e Carle, Cuneo), A. Cognazzo, MD, C. Mocellini, MD, A. Dutto, MD, A. Cucatto, MD (Department of Neurology, Savigliano), C. Cavestro, MD, W. Troni, MD (Department of Neurology, Alba), G. Corso, MD, E. Bottacchi, MD (Department of Neurology, Aosta).     

Horner''s syndrome associated with Guillain-Barré syndrome

Autonomic dysfunctions are classically described during the acute phase of Guillain-Barré syndrome (GBS). This involvement concerns visceral afferent, parasympathetic and/or sympathetic efferent fibers and is closely related to sudden deaths in the acute phase of the disease. We report a case of a patient suffering from a GBS associated with a transient Horner syndrome without extraocular muscle involvement. Pharmacological tests of the pupils pointed to an orthosympathetic pre-ganglionic disturbance. Neither clinical nor electrophysiological parameter suggested a broader involvement of the autonomic nervous system.     

Inflammatory infiltrates in the spinal cord of patients with Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) is defined as an acute inflammatory demyelinating polyradiculoneuropathy (AIDP) of the peripheral nervous system. Reports on central nervous system involvement in patients with GBS are rare and the histopathological analysis was usually restricted to conventional staining techniques. We were able to investigate four cases with GBS at autopsy in respect to the inflammatory infiltrates and histopathological changes in the spinal cord by immunohistochemistry using a panel of antibodies recognizing lymphocytes and different macrophage-activation antigens. There were increased inflammatory cell infiltrates comprising lymphocytes and macrophages in the spinal cord of two cases. In one of these two cases, GBS predominantly affecting the motor system similar to acute motor axonal neuropathy (AMAN) developed following hepatitis B vaccination; in the second one, GBS developed rapidly 4 days after onset of intravenous purified GM1-ganglioside application affecting the motor as well as the sensory system, resembling acute motor sensory axonal neuropathy (AMSAN). Impairment of the spinal anterior horn cells with their axons was suggested to be responsible for prolonged motor symptoms and the predominantly axonal type of neuropathy at least as a late-stage feature in these two cases with fatal outcome. Insignificant cellular infiltrates in the spinal cord were noted in the other two GBS cases. Focal cellular infiltration of spinal nerve roots and meninges was similar in all cases.     

Intravenous immunoglobulin in children with Guillain-Barré syndrome

We report our experience with intravenous immunoglobulin (IVIG), plasmapheresis and supportive care in 13 patients with the Guillain-Barré syndrome. Seven of 13 patients received IVIG, 2 plasmapheresis and 4 supportive care. At 15th day after IVIG administration, all patients in this group had improved at least one disability grade. In the plasmapheresis group, 1 improved at 5th day after the procedure. Two of the 4 patients that received supportive care improved at 20th day of evaluation. In the IVIG group, the final scores were lower and had no relapses. These results suggest faster clinical improvement with IVIG when compared with supportive measures.     

Guillain-Barré syndrome in a patient with primary sicca syndrome

At the age of 23 the patient showed the first signs of dryness syndrome. Those symptoms developed progressively and during a few years primary Sj?gren syndrome was noted. In the 37th year of life suddenly the patient developed very severe Gullian-Barré syndrome with involvement of the peripheral and central nervous system and with a considerable autonomic component. After treatment the patient improved, however mild symptoms of central and peripheral nervous system destruction remained. Those symptoms are still present and the patient is under the care of the Neurology and Rheumatology Clinic.     

Guillain-Barré syndrome in children

In industrialized nations with widespread immunization programs, Guillain-Barré syndrome is the most common cause of acute paralytic illness in children and adults. The incidence of the disease has been estimated to range from 0.5 to 1.5 in 100,000 in individuals less than 18 years of age. Approximately 15% of children with Guillain-Barré syndrome develop respiratory failure and require mechanical ventilatory support. Prospective randomized treatment trials in childhood Guillain-Barré syndrome are wanting; however, smaller case series studies using historical controls suggest that both plasmapheresis and administration of human immunoglobulin could be helpful in reducing morbidity in children with Guillain-Barré syndrome. The prognosis for recovery in children is generally excellent, with the majority of children achieving a complete functional recovery within 6 months from the onset of illness. Studies using an animal model of human Guillain-Barré syndrome, experimental allergic neuritis, have expanded our understanding of the pathogenesis of the disease and suggest new directions for exploration in the treatment of this disorder.     

Progress in Guillain-Barré syndrome

This editorial review summarizes and critically analyses reports published in the preceding 18 months on the pathogenesis of Guillain-Barré syndrome, with particular emphasis on the role of ganglioside antibodies, antecedent infections, and the concept of molecular mimicry. It concludes with an appraisal of currently available and proposed therapies.