CSF Findings in Relation to Clinical Characteristics, Subtype, and Disease Course in Patients With Guillain-Barré Syndrome.

BACKGROUND AND OBJECTIVES: To investigate CSF findings in relation to clinical and electrodiagnostic subtypes, severity, and outcome of Guillain-Barré syndrome (GBS) based on 1,500 patients in the International GBS Outcome Study. METHODS: Albuminocytologic dissociation (ACD) was defined as an increased protein level (>0.45 g/L) in the absence of elevated white cell count (<50 cells/µL). We excluded 124 (8%) patients because of other diagnoses, protocol violation, or insufficient data. The CSF was examined in 1,231 patients (89%). RESULTS: In 846 (70%) patients, CSF examination showed ACD, which increased with time from weakness onset: ≤4 days 57%, >4 days 84%. High CSF protein levels were associated with a demyelinating subtype, proximal or global muscle weakness, and a reduced likelihood of being able to run at week 2 (odds ratio [OR] 0.42, 95% CI 0.25-0.70; p = 0.001) and week 4 (OR 0.44, 95% CI 0.27-0.72; p = 0.001). Patients with the Miller Fisher syndrome, distal predominant weakness, and normal or equivocal nerve conduction studies were more likely to have lower CSF protein levels. CSF cell count was <5 cells/µL in 1,005 patients (83%), 5-49 cells/µL in 200 patients (16%), and ≥50 cells/µL in 13 patients (1%). DISCUSSION: ACD is a common finding in GBS, but normal protein levels do not exclude this diagnosis. High CSF protein level is associated with an early severe disease course and a demyelinating subtype. Elevated CSF cell count, rarely ≥50 cells/µL, is compatible with GBS after a thorough exclusion of alternative diagnoses. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that CSF ACD (defined by the Brighton Collaboration) is common in patients with GBS.

Modified Erasmus GBS Respiratory Insufficiency Score: a simplified clinical tool to predict the risk of mechanical ventilation in Guillain-Barré syndrome.

BACKGROUND: This study aimed to determine the clinical and diagnostic factors associated with mechanical ventilation (MV) in Guillain-Barré syndrome (GBS) and to simplify the existing Erasmus GBS Respiratory Insufficiency Score (EGRIS) for predicting the risk of MV. METHODS: Data from the first 1500 patients included in the prospective International GBS Outcome Study (IGOS) were used. Patients were included across five continents. Patients <6 years and patients from Bangladesh were excluded. Univariable logistic and multivariable Cox regression were used to determine which prespecified clinical and diagnostic characteristics were associated with MV and to predict the risk of MV at multiple time points during disease course. RESULTS: 1133 (76%) patients met the study criteria. Independent predictors of MV were a shorter time from onset of weakness until admission, the presence of bulbar palsy and weakness of neck flexion and hip flexion. The modified EGRIS (mEGRIS) was based on these factors and accurately predicts the risk of MV with an area under the curve (AUC) of 0.84 (0.80-0.88). We internally validated the model within the full IGOS cohort and within separate regional subgroups, which showed AUC values of 0.83 (0.81-0.88) and 0.85 (0.72-0.98), respectively. CONCLUSIONS: The mEGRIS is a simple and accurate tool for predicting the risk of MV in GBS. Compared with the original model, the mEGRIS requires less information for predictions with equal accuracy, can be used to predict MV at multiple time points and is also applicable in less severely affected patients and GBS variants. Model performance was consistent across different regions.

SARS-CoV-2 Vaccination Safety in Guillain-Barré Syndrome, Chronic Inflammatory Demyelinating Polyneuropathy, and Multifocal Motor Neuropathy.

BACKGROUND AND OBJECTIVES: There are concerns on the safety of SARS-CoV-2 vaccination in patients with a history of Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), and multifocal motor neuropathy (MMN). The aim of this study was to determine the risk of recurrence of GBS and exacerbations of CIDP or MMN after SARS-CoV-2 vaccination. METHODS: We conducted a prospective, multicenter cohort study from January 2021 to August 2021. Patients known in 1 of 3 Dutch University Medical Centers with research focus on immune-mediated neuropathy and members of the Dutch Patient Association for Neuromuscular Diseases were invited to participate if they were 18 years or older and diagnosed with GBS, CIDP, or MMN. Participants completed a series of questionnaires at 4 different time points: study baseline (1), within 48 hours before any SARS-CoV-2 vaccination (2 and 3, if applicable), and 6 weeks after their last vaccination (4). Participants unwilling to get vaccinated completed the last questionnaire (4) 4 months after study baseline. We assessed recurrences of GBS, any worsening of CIDP or MMN-related symptoms, treatment alterations, and hospitalization. RESULTS: Of 1,152 individuals to whom we sent the questionnaires, 674 (59%) signed informed consent. We excluded 153 individuals, most often because they had already received a SARS-CoV-2 vaccination or had had the infection (84%) before study baseline. Of 521 participants included in analyses, 403 (81%) completed the last questionnaire (time point 4). None of 162 participants with a history of GBS had a recurrence after vaccination. Of 188 participants with CIDP, 10 participants (5%) reported a worsening of symptoms within 6 weeks after vaccination. In 5 (3%) of these patients, maintenance treatment was modified. Two of 53 participants with MMN (4%) reported a worsening of symptoms, and treatment modification was reported by 1 participant. DISCUSSION: We found no increased risk of GBS recurrence and a low to negligible risk of worsening of CIDP or MMN-related symptoms after SARS-CoV-2 vaccination. Based on our data, SARS-CoV-2 vaccination in patients with these immune-mediated neuropathies seems to be safe.

An International Perspective on Preceding Infections in Guillain-Barré Syndrome: The IGOS-1000 Cohort.

BACKGROUND AND OBJECTIVES: Infections play a key role in the development of Guillain-Barré syndrome (GBS) and have been associated with specific clinical features and disease severity. The clinical variation of GBS across geographical regions has been suggested to be related to differences in the distribution of preceding infections, but this has not been studied on a large scale. METHODS: We analyzed the first 1,000 patients included in the International GBS Outcome Study with available biosamples (n = 768) for the presence of a recent infection with Campylobacter jejuni, hepatitis E virus, Mycoplasma pneumoniae, cytomegalovirus, and Epstein-Barr virus. RESULTS: Serologic evidence of a recent infection with C. jejuni was found in 228 (30%), M. pneumoniae in 77 (10%), hepatitis E virus in 23 (3%), cytomegalovirus in 30 (4%), and Epstein-Barr virus in 7 (1%) patients. Evidence of more than 1 recent infection was found in 49 (6%) of these patients. Symptoms of antecedent infections were reported in 556 patients (72%), and this proportion did not significantly differ between those testing positive or negative for a recent infection. The proportions of infections were similar across continents. The sensorimotor variant and the demyelinating electrophysiologic subtype were most frequent across all infection groups, although proportions were significantly higher in patients with a cytomegalovirus and significantly lower in those with a C. jejuni infection. C. jejuni-positive patients were more severely affected, indicated by a lower Medical Research Council sum score at nadir (p = 0.004) and a longer time to regain the ability to walk independently (p = 0.005). The pure motor variant and axonal electrophysiologic subtype were more frequent in Asian compared with American or European C. jejuni-positive patients (p < 0.001, resp. p = 0.001). Time to nadir was longer in the cytomegalovirus-positive patients (p = 0.004). DISCUSSION: Across geographical regions, the distribution of infections was similar, but the association between infection and clinical phenotype differed. A mismatch between symptom reporting and serologic results and the high frequency of coinfections demonstrate the importance of broad serologic testing in identifying the most likely infectious trigger. The association between infections and outcome indicates their value for future prognostic models.

Guillain-Barré syndrome after SARS-CoV-2 infection in an international prospective cohort study.

In the wake of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, an increasing number of patients with neurological disorders, including Guillain-Barré syndrome (GBS), have been reported following this infection. It remains unclear, however, if these cases are coincidental or not, as most publications were case reports or small regional retrospective cohort studies. The International GBS Outcome Study is an ongoing prospective observational cohort study enrolling patients with GBS within 2 weeks from onset of weakness. Data from patients included in this study, between 30 January 2020 and 30 May 2020, were used to investigate clinical and laboratory signs of a preceding or concurrent SARS-CoV-2 infection and to describe the associated clinical phenotype and disease course. Patients were classified according to the SARS-CoV-2 case definitions of the European Centre for Disease Prevention and Control and laboratory recommendations of the World Health Organization. Forty-nine patients with GBS were included, of whom eight (16%) had a confirmed and three (6%) a probable SARS-CoV-2 infection. Nine of these 11 patients had no serological evidence of other recent preceding infections associated with GBS, whereas two had serological evidence of a recent Campylobacter jejuni infection. Patients with a confirmed or probable SARS-CoV-2 infection frequently had a sensorimotor variant 8/11 (73%) and facial palsy 7/11 (64%). The eight patients who underwent electrophysiological examination all had a demyelinating subtype, which was more prevalent than the other patients included in the same time window [14/30 (47%), P = 0.012] as well as historical region and age-matched control subjects included in the International GBS Outcome Study before the pandemic [23/44 (52%), P = 0.016]. The median time from the onset of infection to neurological symptoms was 16 days (interquartile range 12-22). Patients with SARS-CoV-2 infection shared uniform neurological features, similar to those previously described in other post-viral GBS patients. The frequency (22%) of a preceding SARS-CoV-2 infection in our study population was higher than estimates of the contemporaneous background prevalence of SARS-CoV-2, which may be a result of recruitment bias during the pandemic, but could also indicate that GBS may rarely follow a recent SARS-CoV-2 infection. Consistent with previous studies, we found no increase in patient recruitment during the pandemic for our ongoing International GBS Outcome Study compared to previous years, making a strong relationship of GBS with SARS-CoV-2 unlikely. A case-control study is required to determine if there is a causative link or not.

Long-term follow-up after transatrial-transpulmonary repair of tetralogy of Fallot: influence of timing on outcome.

OBJECTIVES: Our goal was to report the long-term serial follow-up after transatrial-transpulmonary repair of tetralogy of Fallot (TOF) and to describe the influence of the timing of the repair on outcome. METHODS: We included all patients with TOF who had undergone transatrial-transpulmonary repair between 1970 and 2012. Records were reviewed for patient demographics, operative details and events during the follow-up period (death, pulmonary valve replacement, cardiac reinterventions and hospitalization/intervention for arrhythmias). In patients with elective early primary repair of TOF after 1990, a subanalysis of the optimal timing of TOF repair was performed. RESULTS: A total of 453 patients were included (63% male patients; 65% had transannular patch); 261 patients underwent primary elective repair after 1990. The median age at TOF repair was 0.7 years (25th-75th percentile 0.3-1.3) and decreased from 1.7 to 0.4 years from before 1990 to after 2000, respectively (P < 0.001). The median follow-up duration after TOF repair was 16.8 years (9.6-24.7). Events developed in 182 (40%) patients. In multivariable analysis, early repair of TOF (<6 months) [hazard ratio (HR) 3.06; P < 0.001] and complications after TOF repair (HR 2.18; P = 0.006) were found to be predictive for an event. In a subanalysis of the primary repair of TOF after 1990, the patients (n = 125) with elective early repair (<6 months) experienced significantly worse event-free survival compared to patients who had elective repair later (n = 136). In multivariable analysis, early repair (HR 3.00; P = 0.001) and postoperative complications (HR 2.12; P = 0.010) were associated with events in electively repaired patients with TOF. CONCLUSIONS: Transatrial-transpulmonary repair of TOF before the age of 6 months may be associated with more events during the long-term follow-up period.

Long-term outcomes of transatrial-transpulmonary repair of tetralogy of Fallot.

OBJECTIVES: The surgical approach to repair of tetralogy of Fallot (ToF) has shifted over the years. We aimed to report the long-term follow-up after ToF repair with the transatrial-transpulmonary approach and to determine predictors of long-term outcomes. METHODS: Retrospective analysis of patients operated on in two tertiary referral centres. Primary outcome measures were: death, pulmonary valve replacement (PVR), reintervention for other reasons, internal cardiodefibrillator and/or pacemaker placement. Kaplan-Meier assessment of overall and event-free survival as well as uni- and multivariate analyses of risk factors for outcomes were performed. RESULTS: Four hundred and fifty-three patients were included. Median age at operation was: 0.6 years (range 0-19.6) and median age at the last follow-up was 14.3 years (range 0.1-42.1). Median age at repair decreased from 1.2 years (range 0.6-5.8) (1970-80) to 0.3 years (range 0-4.7) (2000-12). A transannular patch (TP) was used in 65% of all patients. The use of a TP showed a decline from 89% in the initial years of the cohort to 64% in 2000-12. Early mortality was 1.1% (5 patients) for the entire cohort and late mortality 2.4% (11 patients). Overall survival for the entire cohort was 97.3% (95% CI 95.7-98.8) and 91.8% (95% CI 85.9-97.7) at 10 and 25 years, respectively. For patients with a TP (n = 294) vs non-TP (n = 159), this was 97.2% (95% CI 95.2-99.2) vs 97.5% (95% CI 95.1-99.9) at 10-year and 91.0% (95% CI 83.9-98.1) vs 96.3% (95% CI 93.0-99.6) at 25-year follow-up (P = 0.958). Fifty-two patients underwent PVR, and in 5 a pacemaker was inserted. Event-free survival for TP versus non-TP patients was 80.2% (95 CI% 75.5-84.9) vs 81.7% (95% CI 75.2-88.2) at 10-year and 27.9% (95% CI 17.7-38.1) vs 78.5% (95% CI 71.4-85.6) at 25-year follow-up (P = 0.016). In multivariate analysis, both the use of a TP (HR 1.705, 95% CI 1.023-2.842) and the year of surgical repair of tetralogy of Fallot (HR 1.039, 95% CI 1.006-1.073) were associated with a higher probability of an event. CONCLUSIONS: ToF patients corrected with the transatrial-transpulmonary approach have good long-term survival. PVR is a frequent event at longer follow-up, and other events are limited. The use of a TP is a predictor for poorer event-free outcomes, increasing the risk of the composite endpoint 1.7 times.