Liselotte Ruts

Clinical features, pathogenesis, and treatment of Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) is an important cause of acute neuromuscular paralysis. Molecular mimicry and a cross-reactive immune response play a crucial part in its pathogenesis, at least in those cases with a preceding Campylobacter jejuni infection and with antibodies to gangliosides. The type of preceding infection and patient-related host factors seem to determine the form and severity of the disease. Intravenous immunoglobulin (IVIg) and plasma exchange are effective treatments in GBS; mainly for practical reasons, IVIg is the preferred treatment. Whether mildly affected patients or patients with Miller Fisher syndrome also benefit from IVIg is unclear. Despite medical treatment, GBS often remains a severe disease; 3-10% of patients die and 20% are still unable to walk after 6 months. In addition, many patients have pain and fatigue that can persist for months or years. Advances in prognostic modelling have resulted in the development of a new and simple prognostic outcome scale that might also help to guide new treatment options, particularly in patients with GBS who have a poor prognosis.

Distinguishing acute-onset CIDP from fluctuating guillain-barré syndrome: A prospective study

Objective: The aim of the study was to provide criteria that can help to distinguish between GBS-TRF and A-CIDP in the early phase of disease. Background: The distinction between Guillain-Barré syndrome (GBS) with fluctuations shortly after start of treatment (treatment-related fluctuations, or GBS-TRF) and chronic inflammatory demyelinating polyneuropathy with acute onset (A-CIDP) is difficult but important because prognosis and treatment strategy largely differ. Methods: Patients with GBS (n = 170) were included in a prospective longitudinal study. Patients with GBS-TRF (n = 16) and patients with A-CIDP (n = 8) were analyzed and compared. Extended clinical data, biologic material, and electrophysiologic data were collected during 1 year follow-up. Results: The first TRF in the GBS-TRF group always occurred within 8 weeks (median 18 days; range 10–54 days) from onset of weakness. In the GBS-TRF group, 5 (31%) patients had a second TRF and none had more TRFs. At all timepoints, patients in the A-CIDP group were less severely affected than patients with GBS-TRF, did not need artificial ventilation, rarely had cranial nerve dysfunction, and tended to have more CIDP-like electrophysiologic abnormalities. More GBS-TRF patients were severely affected and more patients had sensory disturbances when compared to the GBS group without fluctuations. Conclusions: The diagnosis of acute-onset chronic inflammatory demyelinating polyneuropathy (CIDP) should be considered when a patient thought to have Guillain-Barré syndrome deteriorates again after 8 weeks from onset or when deterioration occurs 3 times or more. Especially when the patient remains able to walk independently and has no cranial nerve dysfunction or electrophysiologic features likely to be compatible with CIDP, maintenance treatment for CIDP should be considered.

Distinguishing acute-onset CIDP from Guillain-Barré syndrome with treatment related fluctuations.

Guillain–Barré syndrome (GBS) patients may worsen after initial treatment (treatment-related fluctuation [TRF]). It is difficult to distinguish GBS-TRF from chronic inflammatory demyelinating polyneuropathy with acute onset (A-CIDP). The authors compared 13 patients with A-CIDP with 11 patients with GBS-TRF and concluded that A-CIDP should be suspected when a patient with GBS deteriorates after 9 weeks from onset or when deterioration occurs three times or more. Maintenance treatment should then be considered.

Early recognition of poor prognosis in Guillain-Barré syndrome

Background: Guillain-Barré syndrome (GBS) has a highly diverse clinical course and outcome, yet patients are treated with a standard therapy. Patients with poor prognosis may benefit from additional treatment, provided they can be identified early, when nerve degeneration is potentially reversible and treatment is most effective. We developed a clinical prognostic model for early prediction of outcome in GBS, applicable for clinical practice and future therapeutic trials. Methods: Data collected prospectively from a derivation cohort of 397 patients with GBS were used to identify risk factors of being unable to walk at 4 weeks, 3 months, and 6 months. Potential predictors of poor outcome (unable to walk unaided) were considered in univariable and multivariable logistic regression models. The clinical model was based on the multivariable logistic regression coefficients of selected predictors and externally validated in an independent cohort of 158 patients with GBS. Results: High age, preceding diarrhea, and low Medical Research Council sumscore at hospital admission and at 1 week were independently associated with being unable to walk at 4 weeks, 3 months, and 6 months (all p 0.05–0.001). The model can be used at hospital admission and at day 7 of admission, the latter having a better predictive ability for the 3 endpoints; the area under the receiver operating characteristic curve (AUC) is 0.84–0.87 and at admission the AUC is 0.73–0.77. The model proved to be valid in the validation cohort. Conclusions: A clinical prediction model applicable early in the course of disease accurately predicts the first 6 months outcome in GBS.

Prediction of respiratory insufficiency in Guillain-Barré syndrome

Respiratory insufficiency is a frequent and serious complication of the Guillain‐Barré syndrome (GBS). We aimed to develop a simple but accurate model to predict the chance of respiratory insufficiency in the acute stage of the disease based on clinical characteristics available at hospital admission.

Pain in Guillain-Barre syndrome: a long-term follow-up study.

Background: Pain in Guillain-Barré syndrome (GBS) may be pronounced and is often overlooked. Objectives: To obtain detailed information about pain in GBS and its clinical variants. Methods: This was a prospective cohort study in 156 patients with GBS (including 18 patients with Miller Fisher syndrome [MFS]). We assessed the location, type, and intensity of pain using questionnaires at standard time points during a 1-year follow-up. Pain data were compared to other clinical features and serology. Results: Pain was reported in the 2 weeks preceding weakness in 36% of patients, 66% reported pain in the acute phase (first 3 weeks after inclusion), and 38% reported pain after 1 year. In the majority of patients, the intensity of pain was moderate to severe. Longitudinal analysis showed high mean pain intensity scores during the entire follow-up. Pain occurred in the whole spectrum of GBS. The mean pain intensity was predominantly high in patients with GBS (non-MFS), patients with sensory disturbances, and severely affected patients. Only during later stages of disease, severity of weakness and disability were significantly correlated with intensity of pain. Conclusions: Pain is a common and often severe symptom in the whole spectrum of GBS (including MFS, mildly affected, and pure motor patients). As it frequently occurs as the first symptom, but may even last for at least 1 year, pain in GBS requires full attention. It is likely that sensory nerve fiber involvement results in more severe pain.

Recurrent Guillain–Barré syndrome

Background: Guillain–Barré syndrome (GBS) is generally considered to be monophasic, but recurrences do occur in a presently undefined subgroup of patients. Objectives: To determine which subgroup of patients develops a recurrence and to establish whether preceding infections and neurological symptoms are similar in subsequent episodes. Methods: A recurrence was defined as two or more episodes that fulfilled the NINCDS criteria for GBS, with a minimum time between episodes of 2 months (when fully recovered in between) or 4 months (when only partially recovered). Patients with a treatment-related fluctuation or chronic inflammatory demyelinating polyneuropathy with acute onset were excluded. The clinical characteristics of recurrent GBS patients were compared with those of 476 non-recurrent patients. Results: 32 recurrent GBS patients, who had a total of 81 episodes, were identified. The clinical symptoms in a first episode were similar to the following episodes in individual patients, being GBS or its variant Miller Fisher syndrome (MFS) but never both. While neurological symptoms in subsequent episodes were often similar, the severity of the symptoms and the nature of the preceding infections varied. Recurrent patients (mean age 34.2 years) were younger than non-recurrent patients (mean age 46.9; p = 0.001) and more often had MFS (p = 0.049) or milder symptoms (p = 0.011). Conclusions: Genetic or immunological host factors may play an important role in recurrent GBS, since these patients can develop similar symptoms after different preceding infections. Recurrences occur more frequently in patients under 30, with milder symptoms and in MFS.

Unmyelinated and myelinated skin nerve damage in Guillain–Barré syndrome: Correlation with pain and recovery

Summary Unmyelinated and myelinated skin nerves are diffusely affected in Guillain–Barré syndrome and its variants. Intraepidermal nerve fiber density declines early, remains low over time, correlates with pain severity in the acute phase, and may predict long‐term disability. Abstract We performed a prospective study in 32 patients with Guillain–Barré syndrome (GBS) or its variants to correlate intraepidermal nerve fiber density (IENFD) at the distal leg and lumbar region with pain, autonomic dysfunction, and outcome. In the acute phase, IENFD was reduced in 60% and 61.9% of patients at the distal leg and lumbar region, respectively. In the acute phase, 43.7% of patients complained of neuropathic pain. Their IENFD at the distal leg was significantly lower than in patients without pain (P < .001) and correlated with pain intensity (rs = −0.51; P = .003). Intriguingly, also patients with the pure motor variant of GBS and pain had low IENFD. At 6‐month follow‐up, only 3 patients complained of persisting neuropathic pain, whereas 3 patients reported late‐onset pain symptoms. IENFD in the acute phase did not predict presence or intensity of pain at 6‐month follow‐up. IENFD in the acute phase did not correlate with clinical dysautonomia or GBS severity at nadir. However, it correlated with poorer GBS disability score at 6 months (P = .04), GBS score at nadir (P = .03), and clinically probable dysautonomia (P = .004). At 6‐month follow‐up, median IENFD remained significantly low both at the distal leg (P = .024) and lumbar region (P = .005). Double and triple staining confocal microscope studies showed diffuse damage of myelinated dermal nerves along with axonal degeneration, and mononuclear cell infiltration. Unmyelinated and myelinated skin nerves are diffusely affected in GBS and its variants, including the pure motor form. IENFD declines early, remains low over time, correlates with pain severity in the acute phase, and may predict long‐term disability.

Determination of pain and response to methylprednisolone in Guillain-Barré syndrome

Pain can be a serious problem in patients with Guillain-Barré syndrome (GBS). Different pain symptoms and the effect of methylprednisolone on pain are evaluated.MethodsGBS patients were recruited from a randomized placebo-controlled study comparing intravenous immunoglobulin (IVIg) + methylprednisolone (500 mg for 5 days) versus IVIg + placebo. Presence and severity of pain were prospectively scored at randomization and after 4 weeks. Efficacy of methylprednisolone was evaluated using endpoints: percentage of patients with pain and percentage of patients improving in pain-severity level. Medical records of the subgroup of patients treated in the Erasmus MC were screened retrospectively for different pain symptoms and course. Pain was scored at different time intervals: within 4 weeks before randomization and 0–2, 2–4, 4–24, 24–52 weeks after randomization.Results123 (55%) of 223 patients had pain at randomization. In 70%, pain already started before onset of weakness. Methylprednisolone did not show a positive effect on the presence and reduction of pain. In the subgroup of 39 patients, backache (33%), interscapular (28%), muscle (24%), radicular pain (18%) and painful par-/dysaesthesiae (18%) were most frequently present within the period of 4 weeks before randomization. Twenty-six percent had extreme pain 0–2 weeks after randomization. Most symptoms of pain decreased after this period, but painful par-/dysaesthesiae and muscle pain often remained present during at least 6 months.ConclusionsPain frequently occurs, often starts before onset of weakness and may cause severe complaints. Especially painful par-/dysaesthesiae and muscle pain may persist for months. Methylprednisolone seems to have no significant effect on the presence and intensity of pain.

Treatment of chronic inflammatory demyelinating polyneuropathy

Purpose of reviewChronic inflammatory demyelinating poly(radiculo)neuropathy (CIDP) is a treatable disorder. There are three proven effective treatments available. Randomized controlled trials have only focused on short-term effects, but most patients need long-term therapy. The most up-to-date treatment options are discussed. Attention is also paid to the use of appropriate assessment scales and treatment of residual findings. Recent findingsA Cochrane review is available indicating that intravenous immunoglobulin is an effective treatment. Equal efficacy of intravenous immunoglobulin and steroids was shown during a 6-week treatment period. New open studies indicated possible efficacy for mycophenolate, interferon-β and etanercept. Combinations of treatment are scarcely studied yet. Some CIDP patients may have a more acute onset of disease since maximum severity is reached within 4-8 weeks, resulting in confusion about the diagnosis. It was shown that severe fatigue can be a major complaint in CIDP patients; a training regimen might partially resolve these problems. SummaryCIDP is a treatable disorder, but most patients need long-term treatment. Intravenous immunoglobulin, steroids and plasma exchange are shown to be effective. It is suggested that other immunomodulatory agents can also be effective, but randomized trials are needed to confirm these benefits. General measures to rehabilitate patients and to manage symptoms like fatigue and other residual findings are important.