Patients with chronic inflammatory demyelinating polyneuropathy initially diagnosed as Guillain-Barré syndrome

Progression periods for Guillain-Barré syndrome (GBS) differ from those of chronic inflammatory demyelinating polyneuropathy (CIDP), but physicians could classify patients with CIDP within 4 weeks of onset as GBS. We studied and report the frequency of GBS patients who were later diagnosed as CIDP (11/663, 2%). Plasmapheresis or intravenous immunoglobulin transiently improved all the 11 patients, who 11 progressed slowly or had a relapse beyond the 8 weeks, and the other 2 suffered a relapse between 4 and 8 weeks from the onset. Three patients had had an antecedent infectious illness. CSF albumino-cytological dissociation was detected in 6 patients within 2 weeks of onset. Recognition of the existence of such patients is important for the early diagnosis and treatment of those patients with CIDP for whom GBS has been diagnosed at onset.     

Treatment approaches for Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy

GBS and CIDP are important treatable forms of acquired peripheral neuropathies. GBS is a heterogeneous disorder representing at least five different entities. Three are predominantly motor: AIDP, AMSAN, and AMAN. Fisher syndrome and acute panautonomic neuropathy are other variants. Treatment for all of these conditions is the same and includes either plasma exchange or intravenous immunoglobulin. There is no indication that Guillain-Barré patients respond to corticosteroids. At the present time, it is uncertain if CIDP represents one or more disorders. Evidence favors a syndrome composed of more than one entity accounting for (1) clinical variations from subject-to-subject, ranging from symmetrical to focal neurologic deficits; (2) course variations from slowly progressive to step-wise, to relapsing; and, (3) laboratory variations in nerve conduction studies, spinal fluid protein, and nerve biopsy findings. CIDP patients respond to corticosteroids in contrast to those with GBS. CIDP improves with intravenous immunoglobulin and plasma exchange, paralleling the findings in GBS. Specific regimens of treatment for both GBS and CIDP are presented in this article and considerations that might influence one treatment regimen over another are discussed.     

Antibodies to LM1 and LM1-containing ganglioside complexes in Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy

LM1 is localized in human peripheral nerve myelin. Antibodies to ganglioside complexes (GSCs) have been reported in Guillain-Barré syndrome (GBS). We investigated IgG antibodies to LM1 and two GSCs (GM1 and LMI, or GD1b and LM1) in the sera of each 40 patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and GBS, using ELISA. We detected anti-LM1 antibody in five with GBS and seven with CIDP; anti-GM1/LM1 antibody in three with GBS and one with CIDP; and anti-GD1b/LM1 antibody in two with CIDP. Antibodies to LM1 and LM1-containing GSCs may be among the targets for autoimmunity in GBS and CIDP.     

Altered cerebrospinal fluid index of prealbumin, fibrinogen, and haptoglobin in patients with Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy

Zhang H‐L, Zhang X‐M, Mao X‐J, Deng H, Li H‐F, Press R, Fredrikson S, Zhu J. Altered cerebrospinal fluid index of prealbumin, fibrinogen, and haptoglobin in patients with Guillain–Barré syndrome and chronic inflammatory demyelinating polyneuropathy.
Acta Neurol Scand: 2012: 125: 129–135.
© 2011 John Wiley & Sons A/S. Objectives – Guillain–Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are autoimmune diseases of the peripheral nervous system. A clinical hallmark of GBS and CIDP is the albumino‐cytologic dissociation in the cerebrospinal fluid (CSF). Changes in the CSF levels of proteins other than albumin in patients with GBS and CIDP are not as well studied. If altered, aberrant levels of CSF proteins may render it possible to establish useful biomarkers for GBS and CIDP. Materials and methods – Enzyme‐linked immunosorbent assay (ELISA) was used to measure the levels of prealbumin, fibrinogen, haptoglobin, apolipoprotein E, apolipoprotein A4 in both CSF and plasma samples from 19 patients with GBS and eight with CIDP, 24 controls with multiple sclerosis (MS) as well as 20 patients with other non‐inflammatory neurological disorders (OND). Results – The levels of prealbumin in both the plasma and the CSF were elevated in patients with GBS and MS compared with the controls. The higher levels of fibrinogen were seen in the CSF of patients with GBS and CIDP, but not in the plasma. The levels of CSF prealbumin and fibrinogen, measured by the CSF index of these proteins, were lower in patients with GBS and that of fibrinogen in patients with CIDP compared with controls with OND. Haptoglobin levels in the CSF rather than in the plasma were higher in patients with GBS and CIDP than in controls. The CSF haptoglobin index was higher in patients with CIDP and MS, but not in those with GBS. No correlation was found between levels of CSF proteins and clinical parameters in patients with GBS and CIDP. Conclusions – Our data provide preliminary evidence that GBS is associated with low CSF index levels of prealbumin and fibrinogen, but normal levels of haptoglobin, whereas CIDP is associated with normal CSF index levels of prealbumin, low fibrinogen, and high levels of haptoglobin. Further studies are needed to identify the underlying mechanisms behind these CSF protein alterations and to clarify whether prealbumin, fibrinogen, and haptoglobin can serve as useful biomarkers for GBS and CIDP.     

Dendritic cells in the cerebrospinal fluid and peripheral nerves in Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy

The role of antigen-presenting cells (APC) involved in induction of T and B cell mediated autoaggressive immunity in Guillain-Barre syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is poorly understood. We studied the numbers and phenotype of dendritic cells (DC) in blood and cerebrospinal fluid (CSF) over the course of GBS and CIDP before and after immunomodulatory treatment. Four out of seven GBS patients examined prior to treatment with high-dose intravenous immunoglobulins (IvIg) had elevated numbers of CD123(+) plasmacytoid DC in the CSF, while both GBS and CIDP patients examined prior to treatment had elevated numbers of CD11c(+) myeloid DC in the CSF, as compared to patients with noninflammatory neurological diseases (OND). The percentages of blood DC expressing the cell surface marker CD1a, co-stimulatory molecules CD80 and CD86, adhesion molecule CD54, and chemokine receptors CCR1, CCR2, CCR5, and CXCR4 were not affected in GBS or CIDP. The immunohistochemistry of sural nerve biopsies revealed CD11c(+)CD83(-)CD14(-)CD16(-) immature myeloid DC at low numbers, mostly in the perineurium, without difference between CIDP patients and controls. In contrast, the numbers of CD11c(+)CD14(+)/CD16(+) macrophages were higher within the endoneurium in CIDP patients compared with the controls. The recruitment of DC to CSF in GBS and CIDP may be important in capturing antigens released from inflamed spinal nerve roots into CSF and in transferring these antigens from CSF to local lymph nodes, where naive T and B cells may be activated.     

Autonomic function in demyelinating and axonal subtypes of Guillain-Barré syndrome

OBJECTIVES: To investigate whether or not the pattern and extent of autonomic involvement differ between the two subtypes of Guillain-Barré syndrome (GBS), namely acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). METHODS: Head-up tilt test, R-R interval variation, plasma noradrenaline concentration, skin vasomotor reflex (SVR) and sympathetic sweat response (SSwR) were used to estimate autonomic function in seven AIDP and eight AMAN patients. RESULTS: Heart rate and plasma noradrenaline concentration were significantly high in the AIDP group but not in the AMAN group. Skin vasomotor reflexes were generally preserved and SSwRs were impaired in patients with severe neurological deficits for both AIDP and AMAN groups. CONCLUSION: The patterns of autonomic involvement are qualitatively different between AIDP and AMAN. Acute inflammatory demyelinating polyneuropathy is characterized by cardio-sympathetic hyperactivity, excessive or reduced sudomotor function and preserved skin vasomotor function, while AMAN is not necessarily generally associated with marked autonomic dysfunction except for the sudomotor hypofunction seen in patients with severe neurological deficits.     

Outcome of axonal and demyelinating forms of Guillain-Barré syndrome in children

Previous reports have suggested that outcome is worse in the axonal compared with the demyelinating form of Guillain-Barré syndrome (GBS). We performed a retrospective study of 23 children with electrophysiologically confirmed cases of predominant subtypes of GBS to investigate this issue. The patients were classified based on the electrodiagnostic features: Ten (44%) had acute inflammatory demyelinating polyradiculoneuropathy, eight (35%) had acute motor axonal neuropathy, and five (21%) had acute motor-sensory axonal neuropathy. All patients received a standard intravenous immunoglobulin therapy (0.4 g /kg /day for 5 consecutive days). In the acute phase of the disease, patients with the axonal forms of GBS were more disabled than were those with the demyelinating GBS, as measured by GBS scores. Mechanical ventilation was required in five (38%) patients in the axonal group compared with one (10%) patient in the demyelinating group. There was no significant difference at 6 months in GBS scores between demyelinating and axonal forms of GBS. All 20 survivors recovered completely by 12 months. After standard intravenous immunoglobulin therapy, children with axonal forms of GBS recover more slowly than those with the demyelinating form, but outcome at 12 months appears to be equally favorable in two groups.     

Studies of HLA associations in male and female patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)

HLA associations are found to differ with the gender of the patient in some autoimmune diseases. Here we have investigated whether there are gender-related HLA associations in Guillain–Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), both of which occur more frequently in male patients than in females. In GBS, no particular HLA associations were noted, except for a slight negative association in both males and females for carriage of HLA-DR5. In CIDP, the gene frequency and the frequency of individuals positive for HLA-DR2 were greater in female patients than female controls, although this was statistically significant only for the gene frequency. Furthermore more female CIDP patients were homozygous for DR2, than male CIDP patients, or male or female controls and patients with GBS. This suggests that sex-related factors may interact with the risk associated with carriage of HLA-DR2 for development of CIDP.     

Treatment of Guillain-Barré syndrome and CIDP

Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating poly-(radiculo)neuropathy (CIDP) are immune-mediated disorders with a variable duration of progression and a range in severity of weakness. Infections can trigger GBS and exacerbate CIDP. Anti-ganglioside antibodies are important, but there is debate on the role of genetic factors in the pathogenesis of these disorders. Randomized controlled trials (RCT) have shown that intravenous immunoglobulin (IVIg) and plasma exchange (PE) are effective in both GBS and CIDP. Most CIDP patients also improve after steroid therapy. Despite current treatment options, many patients have residual deficits or need to be treated for a long period of time. Therefore, new treatment trials are highly indicated. This review focuses on the current and possible new treatment options that could be guided by recent results from laboratory experiments.     

Chronic progressive axonal polyneuropathy simulating Guillain-Barré syndrome.

Six cases of chronic progressive and/or relapsing polyneuropathy are reported. All cases were idiopathic at the beginning of observation. Electrophysiological examination and biopsy of sural nerve in all cases as well as autopsy of spinal roots S1 in case 6 showed loss of fibers and axonal degeneration of myelinated fibers but neither active demyelination nor inflammatory cells were observed. Chronic progressive or relapsing idiopathic axonal polyneuropathy appear to be a distinct entity different from GBS. The term "axonal GBS" seems to be questionable.     

Motor and sensory demyelinating mononeuropathy multiplex (multifocal motor and sensory demyelinating neuropathy): a separate entity or a variant of chronic inflammatory demyelinating polyneuropathy?

We report 16 patients with motor and sensory demyelinating mononeuropathy multiplex (MSDMM) or multifocal motor and sensory demyelinating neuropathy (MMSDN). These patients had the clinical pattern of motor and sensory mononeuropathy multiplex, electrophysiological evidence of demyelination including conduction block, and segmental demyelination in the sural nerve biopsy. Sixty per cent of patients had high CSF protein. Eighty per cent of patients showed good responsiveness to steroid treatment. Unlike multifocal motor neuropathy (MMN), MSDMM is characterized by a shorter course, sensory deficits and sensory nerve conduction abnormalities, absence of GM1 antibody in most patients tested, and a good response to steroid therapy. We believe that MSDMM represents a variant of chronic inflammatory demyelinating polyneuropathy (CIDP) and an intermediate link between CIDP and MMN.     

History of Guillain-Barré syndrome

1916: birth in Paris of a modest syndrome presented to a weekly meeting of the Société Médicale by Georges Guillain, Jean-Alexandre Barré and André Strohl. 1981: glorification of the syndrome as a world event in Santa Inez Valley at the International Conference held under the auspices of the Kroc Foundation. This is indeed a long way from a few clinicians and internists to the representatives of all branches of the Neurological Sciences for "la radiculo-névrite avec dissociation albumino-cytologique à évolution spontanément régressive "studied in two soldiers of the Vth French Army. Every neurologist from clinician to researcher currently knows this model of inflammatory and demyelinating diseases of the peripheral nervous system and the pros and cons of cellular vs humeral immunity which are presumed to be its pathophysiological process. What is less known is "la petite histoire" i.e. that of men and events which surrounded its birth and growth to being an entity. Why did André Strohl disappear? Who were L. Duménil and O. Landry? Should we say Guillain-Barré?, Landry-Guillain-Barré?, Duménil-Landry-Guillain-Barré? Unexpected or poorly known facts are not lacking in this story the last of which being that most references to that most French syndrome are to be found in English and American books.