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R D Hadden

Publications and source records attributed to R D Hadden.

12 recordsLinked to original sources
PubMed2001

Guillain-Barré syndrome serum and anti-Campylobacter antibody do not exacerbate experimental autoimmune neuritis.

To investigate whether antibodies are pathogenic in Guillain-Barré syndrome (GBS), we injected pre-treatment serum from 11 GBS patients intraperitoneally into rats in which the blood-nerve barrier had been opened by induction of mild adoptive transfer experimental autoimmune neuritis. There was no significant clinical, neurophysiological or pathological difference between rats receiving GBS serum compared with those receiving control serum, except that GBS serum caused minor excess weight loss. Murine monoclonal antibody to Campylobacter jejuni and gangliosides also did not exacerbate disease. This experiment failed to show antibody-mediated disease exacerbation and so does not support an antibody-mediated mechanism in GBS.

Animals↗
PubMed2001

Preceding infections, immune factors, and outcome in Guillain-Barré syndrome.

OBJECTIVE: To test the hypothesis that different preceding infections influence the neurophysiologic classification and clinical features of Guillain-Barré syndrome (GBS). METHODS: We tested pretreatment sera, 7 +/- 3 (mean +/- SD) days from onset, from 229 patients with GBS in a multicenter trial of plasma exchange and immunoglobulin, for serological markers of infection, adhesion molecules, and cytokine receptors, and compared these with neurophysiologic and clinical features. RESULTS: Recent infection by Campylobacter jejuni was found in 53 patients (23%), cytomegalovirus in 19 (8%), and Epstein-Barr virus in four (2%). Patients with C. jejuni infection were more likely than others to have neurophysiologic criteria of axonal neuropathy or inexcitable nerves, antiganglioside GM(1) antibodies, pure motor GBS, lower CSF protein, and worse outcome. Patients with cytomegalovirus infection were younger and more likely than others to have raised serum concentrations of molecules important in T lymphocyte activation and migration, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble leukocyte selectin, and soluble interleukin-2 receptor (sIL-2R). Concentrations of sICAM-1 and soluble tumor necrosis factor receptor were higher in patients with inexcitable nerves than those with demyelinating neurophysiology. Logistic regression analysis showed death or inability to walk unaided at 48 weeks were associated with diarrhea, inexcitable nerves, severe arm weakness, age over 50, raised sIL-2R concentration and absence of immunoglobulin (Ig) M antiganglioside GM(1) antibodies. CONCLUSIONS: Subtypes of GBS defined by preceding infections were only approximately associated with different patterns of clinical, neurophysiologic, and immunologic features. A single infectious agent caused more than one type of pathology in GBS, implying interaction with additional host factors. Most patients had no identified infection.

Antibodies↗
PubMed2000

Randomized controlled trial of brain-derived neurotrophic factor in Guillain-Barré syndrome: a pilot study.

Brain-derived neurotrophic factor (BDNF) has the theoretical potential to protect neurones from axonal degeneration. The objective of this study was to discover whether brain-derived neurotrophic factor is safe in Guillain-Barré syndrome, and to make preliminary observations of its efficacy. This was a parallel group randomized controlled trial of subcutaneous brain-derived neurotrophic factor 25 microg/kg daily compared with placebo for up to 24 weeks or until patients could walk without aid. Six patients received brain-derived neurotrophic factor, of whom three had serious adverse events including one death. Four patients received placebo, of whom two had serious adverse events including one death. The rate and extent of recovery were similar in the two groups. This pilot study did not detect any serious adverse events attributed to brain-derived neurotrophic factor treatment.

Adolescent↗
PubMed1999

Randomized trial of interferon beta-1a in chronic inflammatory demyelinating polyradiculoneuropathy.

OBJECTIVE: To test the safety and efficacy of interferon beta-1a (IFN-beta) in treatment-resistant chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). BACKGROUND: Current treatment regimens leave 4% to 30% of patients with CIDP with moderate or severe disability. IFN-beta has been reported as beneficial in one treatment-resistant patient. METHODS: Ten consecutive treatment-resistant patients were randomized in a double-blind, crossover design to receive placebo or IFN-beta (3 MIU for 2 weeks and then 6 MIU for 10 weeks) subcutaneously three times weekly, followed by 4 weeks without treatment, and then the opposite treatment for 12 weeks. The primary outcome measure was "clinically important" improvement by specified amounts in any three of eight clinical measures: timed 10-m walk, Ambulation Index, expanded Medical Research Council sum score, nine-hole peg test time, Functional Independence Measure, Hammersmith Motor Ability, a new Guy's Neurological Disability Scale, and the EuroQoL quality-of-life scale. These and motor median nerve conduction studies were measured before and after 12 weeks of each treatment. RESULTS: Clinically important improvement was observed in one patient while taking IFN-beta and two patients while taking placebo. There was no significant difference between IFN-beta and placebo in the change in any of the individual clinical or neurophysiological measures between the beginning and end of treatment. There were no serious adverse events. CONCLUSION: This trial shows that IFN-beta is safe but not efficacious in treatment-resistant CIDP.

Adjuvants, Immunologic↗
PubMed1999

Pathogenesis of Guillain-Barré syndrome.

Recent neurophysiological and pathological studies have led to a reclassification of the diseases that underlie Guillain-Barré syndrome (GBS) into acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor and sensory axonal neuropathy (AMSAN) and acute motor axonal neuropathy (AMAN). The Fisher syndrome of ophthalmoplegia, ataxia and areflexia is the most striking of several related conditions. Significant antecedent events include Campylobacter jejuni (4-66%), cytomegalovirus (5-15%), Epstein-Barr virus (2-10%), and Mycoplasma pneumoniae (1-5%) infections. These infections are not uniquely associated with any clinical subtype but severe axonal degeneration is more common following C. jejuni and severe sensory impairment following cytomegalovirus. Strong evidence supports an important role for antibodies to gangliosides in pathogenesis. In particular antibodies to ganglioside GM1 are present in 14-50% of patients with GBS, and are more common in cases with severe axonal degeneration associated with any subtype. Antibodies to ganglioside GQ1b are very closely associated with Fisher syndrome, its formes frustes and related syndromes. Ganglioside-like epitopes exist in the bacterial wall of C. jejuni. Infection by this and other organisms triggers an antibody response in patients with GBS but not in those with uncomplicated enteritis. The development of GBS is likely to be a consequence of special properties of the infecting organism, since some strains such as Penner 0:19 and 0:41 are particularly associated with GBS but not with enteritis. It is also likely to be a consequence of the immunogenetic background of the patient since few patients develop GBS after infection even with one of these strains. Attempts to match the subtypes of GBS to the fine specificity of anti-ganglioside antibodies and to functional effects in experimental models continue but have not yet fully explained the pathogenesis. T cells are also involved in the pathogenesis of most or perhaps all forms of GBS. T cell responses to any of three myelin proteins, P2, PO and PMP22, are sufficient to induce experimental autoimmune neuritis. Activated T cells are present in the circulation in the acute stage, up-regulate matrix metalloproteinases, cross the blood-nerve barrier and encounter their cognate antigens. Identification of the specificity of these T cell responses is still at a preliminary stage. The invasion of intact myelin sheaths by activated macrophages is difficult to explain according to a purely T cell mediated mechanism. The different patterns of GBS are probably due to the diverse interplay between antibodies and T cells of differing specificities.

Animals↗
PubMed1999

Treatment of immune-mediated inflammatory neuropathies.

Experimental models have suggested potential new treatments for human inflammatory neuropathy, but current practice is largely based on empirical trials. Evidence from randomized trials supports the use of intravenous immunoglobulin in Guillain-Barré syndrome, chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy with conduction block (MMNCB). In Guillain-Barré syndrome and CIDP intravenous immunoglobulin is equivalent to but more convenient than plasma exchange. In MMNCB adequate comparative studies of intravenous immunoglobulin and plasma exchange have not been performed. Corticosteroid treatment is beneficial in CIDP, but not in Guillain-Barré syndrome and may worsen MMNCB. More randomized trials and systematic reviews are needed to improve the evidence base for clinical practice.

Adrenal Cortex Hormones↗
PubMed1998

Electrophysiological classification of Guillain-Barré syndrome: clinical associations and outcome. Plasma Exchange/Sandoglobulin Guillain-Barré Syndrome Trial Group.

We performed electrophysiological and serological testing within 15 days of symptom onset on 369 patients with Guillain-Barré Syndrome (GBS) enrolled in a trial comparing plasma exchange, intravenous immunoglobulin, and both treatments. Patients were classified into five groups by motor nerve conduction criteria; 69% were demyelinating, 3% axonal, 3% inexcitable, 2% normal, and 23% equivocal. Six of 10 (60%) patients with axonal neurophysiology had had a preceding diarrheal illness compared with 71 of 359 (20%) in other groups. Antiganglioside GM1 antibodies were present in a higher proportion of patients with axonal physiology or inexcitable nerves than other patients. The number dead or unable to walk unaided at 48 weeks was greater in the group with initially inexcitable nerves (6 of 12, 50%) compared with the rest (52 of 357, 15%), but was not significantly different between the axonal (1 of 10, 10%) and demyelinating (44 of 254, 17%) groups. Sensory action potentials and clinical sensory examination were both normal in 53 of 342 (16%) patients, and these "pure motor GBS" patients were more likely than other GBS patients to have IgG antiganglioside GM1 antibodies and to have had preceding diarrhea but had a similar outcome. The axonal group was more likely than other groups to have normal sensory action potentials. The outcomes in response to the three treatments did not differ in any subgroup (including patients with pure motor GBS or preceding diarrhea) or any neurophysiological category.

Autoantibodies↗
PubMed1998

Guillain-Barré syndrome: recent advances.

Guillain-Barré syndrome is an autoimmune disease of peripheral nerves. Sufferers may require prolonged intensive care and may be permanently disabled. New understanding of the aetiology is revealing different pathological subtypes and helping predict the outcome. Recent advances have improved immunomodulatory and general treatment.

Critical Care↗