Rinske van Koningsveld

A clinical prognostic scoring system for Guillain-Barré syndrome.

BACKGROUND Guillain-Barré syndrome (GBS) is an acute post-infectious immune-mediated peripheral neuropathy with a highly variable clinical course and outcome. We aimed to develop and validate a scoring system based on clinical characteristics in the acute phase of GBS to predict outcome at 6 months. METHODS We studied patients with GBS who were unable to walk independently. A derivation set included 388 patients from two randomised controlled trials and one pilot study. Potential predictors were assessed for their association with the inability to walk independently at 6 months. A simple clinical scoring system was developed on the basis of regression coefficients of predictors in a multivariable logistic regression model. Model performance was quantified with respect to discrimination (area under receiver operating characteristics curve, AUC) and calibration (graphically). We validated our scoring system in a set of 374 patients from another randomised trial. FINDINGS We included three variables that were predictive of poor outcome at 6 months in our model: age, preceding diarrhoea, and GBS disability score at 2 weeks after entry. Scores ranged from 1 to 7, with three categories for age, two for diarrhoea, and five for GBS disability score at 2 weeks. Predictions corresponding to these prognostic scores ranged from 1% to 83% for the inability to walk independently at 6 months. Predictions agreed well with observed outcome frequencies (adequate calibration) and showed a very good discriminative ability (AUC 0.85) in both data sets. INTERPRETATION A simple scoring system for patients with GBS, based on three clinical characteristics, accurately predicts outcome at 6 months. The system could be used to counsel individual patients and identify high-risk groups to guide future trials.

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.

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.

Modifying the Medical Research Council grading system through Rasch analyses

The Medical Research Council grading system has served through decades for the evaluation of muscle strength and has been recognized as a cardinal feature of daily neurological, rehabilitation and general medicine examination of patients, despite being respectfully criticized due to the unequal width of its response options. No study has systematically examined, through modern psychometric approach, whether physicians are able to properly use the Medical Research Council grades. The objectives of this study were: (i) to investigate physicians’ ability to discriminate among the Medical Research Council categories in patients with different neuromuscular disorders and with various degrees of weakness through thresholds examination using Rasch analysis as a modern psychometric method; (ii) to examine possible factors influencing physicians’ ability to apply the Medical Research Council categories through differential item function analyses; and (iii) to examine whether the widely used Medical Research Council 12 muscles sum score in patients with Guillain–Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy would meet Rasch models expectations. A total of 1065 patients were included from nine cohorts with the following diseases: Guillain–Barré syndrome (n = 480); myotonic dystrophy type-1 (n = 169); chronic inflammatory demyelinating polyradiculoneuropathy (n = 139); limb-girdle muscular dystrophy (n = 105); multifocal motor neuropathy (n = 102); Pompes disease (n = 62) and monoclonal gammopathy of undetermined related polyneuropathy (n = 8). Medical Research Council data of 72 muscles were collected. Rasch analyses were performed on Medical Research Council data for each cohort separately and after pooling data at the muscle level to increase category frequencies, and on the Medical Research Council sum score in patients with Guillain–Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy. Disordered thresholds were demonstrated in 74–79% of the muscles examined, indicating physicians’ inability to discriminate between most Medical Research Council categories. Factors such as physicians’ experience or illness type did not influence these findings. Thresholds were restored after rescoring the Medical Research Council grades from six to four options (0, paralysis; 1, severe weakness; 2, slight weakness; 3, normal strength). The Medical Research Council sum score acceptably fulfilled Rasch model expectations after rescoring the response options and creating subsets to resolve local dependency and item bias on diagnosis. In conclusion, a modified, Rasch-built four response category Medical Research Council grading system is proposed, resolving clinicians’ inability to differentiate among its original response categories and improving clinical applicability. A modified Medical Research Council sum score at the interval level is presented and is recommended for future studies in Guillain–Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy.

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.

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.

Pain accompanies pure motor Guillain-Barré syndrome

Dear Editor, In Guillain-Barré syndrome (GBS), pain is frequently present and can even be misleading in making the diagnosis (Ropper and Shahani, 1984; Pentland and Donald, 1994; Moulin et al., 1997; Ruts et al., 2007). Clinicians generally associate pain with affected sensory nerves and not with a pure motor neuropathy. We investigated whether pain also occurs in the pure motor variant of GBS in a large group of GBS patients from Europe and Curacxao because this could increase awareness and ultimately improve insight into mechanisms of pain in GBS. The European GBS patients (predominantly Dutch; GBS disability score 3) were recruited from a doubleblind, placebo-controlled randomized, multicenter study between 1994 and 2000 (van Koningsveld et al., 2004). The presence and severity of pain were prospectively collected. In Curacxao, where we previously described the predominant occurrence of pure motor GBS, we retrospectively screened the medical records of all GBS cases who had been admitted to the island’s only neurological department between 1987 and 2006 (van Koningsveld et al., 2001). In all cases, the presence of pain had been collected from the period ranging from hospital admission until 4 weeks later. The clinical differentiation between the motor and the sensory-motor variant was made on the presence of sensory signs or symptoms by standard neurological examination. On the basis of electromyographic (EMG) studies, performed within 4 weeks after admission, we also tried to classify the patients as demyelinating [acute inflammatory demyelinating polyneuropathy (AIDP)] or axonal [acute motor axonal neuropathy (AMAN)] (Ho et al., 1995; Hadden et al., 1998). When the EMG was not conclusive, the patient was classified as ‘not conclusive.’ Because we were primarily interested in whether pain also occurs in GBS patients with pure motor neuropathy, only the clinical pure motor neuropathy and AMAN patients were further specified in this study. We studied 225 European and 83 GBS patients from Curacxao. Age, sex, maximum GBS disability score, and the percentage of patients reporting pain were not significantly different between the two groups (Table 1). The percentage of patients with a clinically pure motor neuropathy (72 vs. 8%) and AMAN based on the available EMG data (16 vs. 2%) was higher in the GBS population from Curacxao comparable with an earlier study, suggesting a probable relationship with an increased percentage of preceding gastroenteritis (van Koningsveld et al., 2001). Also in the present study, the percentage of preceding diarrhea was higher in the GBS patients from Curacxao. Of the total group of 77 patients from Europe and

Immunotherapy for Guillain-Barrè syndrome

1it is characterised by rapid and progressive weakness in the extremities and sensory deficit in most patients. The cause of GBS is unknown but about three-quarters of patients report an infection in the 3 weeks before disease onset. Weakness peaks within 4 weeks, and recovery begins within several weeks or months. GBS can be severe and, despite treatment, about 25% of patients need artificial ventilation for some time, and about 20% of patients are still unable to walk unaided after 6 months. Many patients remain severely fatigued for many years. Treatments for GBS include intravenous immunoglobulin (IVIg) and plasma exchange (PE). A practical guideline on immunotherapy for GBS was recently published to help physicians manage patients with this disorder. Hughes and colleagues, 2 as part of the Quality Standards Subcommittee of the American Academy of Neurology, have assesssed all the treatment trials in GBS that had been published up to March, 2002. Data on treatment with PE, IVIg, and steroids were mainly obtained from the Cochrane Database of systematic reviews. 3–5 Most of these trials have used improvement on the GBS disability scale 4 weeks after start of treatment as an outcome measure. However, the success of this criterion is dependent on the assumption that large functional improvements occur during the first few weeks of treatment. In a Cochrane systematic review, 3