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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., (© 2023 American Academy of Neurology.)

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., (© 2022 American Academy of Neurology.)

Background and Objectives: The clinical course and outcome of the Guillain-Barré syndrome (GBS) are diverse and vary among regions. The modified Erasmus GBS Outcome Score (mEGOS), developed with data from Dutch patients, is a clinical model that predicts the risk of walking inability in patients with GBS. The study objective was to validate the mEGOS in the International GBS Outcome Study (IGOS) cohort and to improve its performance and region specificity., Methods: We used prospective data from the first 1,500 patients included in IGOS, aged ≥6 years and unable to walk independently. We evaluated whether the mEGOS at entry and week 1 could predict the inability to walk unaided at 4 and 26 weeks in the full cohort and in regional subgroups, using 2 measures for model performance: (1) discrimination: area under the receiver operating characteristic curve (AUC) and (2) calibration: observed vs predicted probability of being unable to walk independently. To improve the model predictions, we recalibrated the model containing the overall mEGOS score, without changing the individual predictive factors. Finally, we assessed the predictive ability of the individual factors., Results: For validation of mEGOS at entry, 809 patients were eligible (Europe/North America [n = 677], Asia [n = 76], other [n = 56]), and 671 for validation of mEGOS at week 1 (Europe/North America [n = 563], Asia [n = 65], other [n = 43]). AUC values were >0.7 in all regional subgroups. In the Europe/North America subgroup, observed outcomes were worse than predicted; in Asia, observed outcomes were better than predicted. Recalibration improved model accuracy and enabled the development of a region-specific version for Europe/North America (mEGOS-Eu/NA). Similar to the original mEGOS, severe limb weakness and higher age were the predominant predictors of poor outcome in the IGOS cohort., Discussion: mEGOS is a validated tool to predict the inability to walk unaided at 4 and 26 weeks in patients with GBS, also in countries outside the Netherlands. We developed a region-specific version of mEGOS for patients from Europe/North America., Classification of Evidence: This study provides Class II evidence that the mEGOS accurately predicts the inability to walk unaided at 4 and 26 weeks in patients with GBS., Trial Registration Information: NCT01582763., (© 2021 American Academy of Neurology.)

Objective: The objective of this study was to explore the extent of IV immunoglobulin (IVIG) treatment-related fluctuations (TRFs) by using home collection of daily grip strength in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and to use that information to develop evidence-based treatment optimization strategies., Methods: This prospective observational study included 25 patients with well-defined CIDP. Participants recorded grip strength daily for 6 months. Disability and gait metrics were collected weekly. Serum immunoglobulin G levels were obtained at peak, trough, and midcycle IVIG intervals. Day-to-day grip strength changes <10% were considered random. To identify patients with TRFs, 3-day averaged grip strength was calculated on each consecutive day after an IVIG infusion. TRFs were defined as ≥10% 3-day averaged grip strength difference compared to the pre-IVIG baseline., Results: Participants successfully recorded grip strength on all but 9% of recordable days. Twelve patients (48%) were classified as low/no fluctuaters and 13 (52%) as frequent fluctuaters. In the frequent fluctuating group, grip strength improved over 1 week and thereafter was relatively stable until the third week after infusion. Grip strength was significantly correlated with measures of disability., Conclusions: Grip strength collection by patients at home is reliable, valid, and feasible. A change in grip strength by ≥10% is a useful, practical, and evidence-based approach that may be used to identify clinically meaningful TRFs. From these data, we propose a treatment optimization strategy for patients with CIDP on chronic IVIG that may be applied to routine clinic care during both face-to-face and virtual video or telephone patient encounters., Trial Registration Information: ClinicalTrials.gov Identifier: NCT02414490., (© 2021 American Academy of Neurology.)

Objectives: We performed responsiveness comparison between the patient-reported Inflammatory Rasch-built Overall Disability Scale (I-RODS) and the widely used clinician-reported Inflammatory Neuropathy Cause and Treatment-Overall Neuropathy Limitation Scale (INCAT-ONLS) in patients with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and immunoglobulin M-monoclonal gammopathy of undetermined significance related polyneuropathy (IgM-MGUSP)., Methods: One hundred thirty-seven patients (GBS: 55, CIDP: 59, IgM-MGUSP: 23) with a new diagnosis or clinical relapse assessed both scales. Patients with GBS/CIDP were examined at 0, 1, 3, 6, and 12 months; patients with IgM-MGUSP at 0, 3, and 12. We subjected all data to Rasch analyses, and calculated for each patient the magnitude of change on both scales using the minimal clinically important difference (MCID) related to the individual standard errors (SEs). A responder was defined as having an MCID-SE ≥1.96. Individual scores on both measures were correlated with the EuroQoL thermometer (heuristic responsiveness)., Results: The I-RODS showed a significantly higher proportion of meaningful improvement compared with the INCAT-ONLS findings in GBS/CIDP. For IgM-MGUSP, the lack of responsiveness during the 1-year study did not allow a clear separation. Heuristic responsiveness was consistently higher with the I-RODS., Conclusion: The I-RODS more often captures clinically meaningful changes over time, with a greater magnitude of change, compared with the INCAT-ONLS disability scale in patients with GBS and CIDP. The I-RODS offers promise for being a more sensitive measure and its use is therefore suggested in future trials involving patients with GBS and CIDP., (© 2014 American Academy of Neurology.)

The safety and efficiency of a novel method of rapid-infusion IV immunoglobulin (IVIg) were retrospectively reviewed in 50 patients with neuromuscular disorders. There were 89 adverse events after 341 rapid infusions (26%), 3.5% of which were considered to be major (requiring hospitalization) and 66% minor. All patients recovered without sequelae, and there were no deaths. Fourteen of 17 patients (82%) receiving maintenance therapy preferred rapid IVIg infusion because of its convenience. Rapid-infusion IVIg can be given safely and conveniently in many patients with neuromuscular disorders.

We performed an open-label, prospective, pilot study of interferon (IFN)-alpha 2a treatment for 6 weeks in 16 patients with chronic inflammatory demyelinating polyneuropathy (CIDP). All patients had failed to improve or relapsed after treatment with at least one conventional therapy (steroids, IV gamma globulin, or plasma exchange). Assessment included MRC strength score, leg sensory score, grip dynanometry, Rankin disability score, electrodiagnostic studies, and serum concentration of tumor necrosis factor-alpha. Nine (56%) improved after IFN-alpha therapy. Mean MRC score increased by 4.2 points (p = 0.01), and mean sensory score improved by 2.3 points (p = 0.02). Five patients improved five or more points on the MRC score, nine had slight improvement or were unchanged, and two worsened. We conclude that IFN-alpha may be effective in some patients with CIDP who relapse or fail to respond to conventional immunomodulating therapy.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a progressive or relapsing immune-mediated neuropathy usually responsive to plasma exchange, intravenous gammaglobulin or steroids, with some patients being refractory to these conventional therapies. We report a patient with CIDP who had spontaneous improvement after an episode of sepsis, but subsequently relapsed with severe generalized weakness; he was unresponsive to the conventional treatments for CIDP but had dramatic improvement following treatment with interferon-alpha 2A. Nerve conduction studies following treatment showed improved distal compound muscle action potential amplitudes without change in the degree of conduction block. The mechanism of action of interferon-alpha is unknown, but it may modulate proinflammatory cytokines that have a role in immune-mediated demyelination. Interferon-alpha may be an effective alternative therapy in patients with CIDP who relapse or are refractory to conventional treatments.

We report the clinical and EMG details of 67 consecutive patients with strictly defined chronic inflammatory demyelinating polyneuropathy (CIDP) during a 4-year period and compare responses to treatment in patients with idiopathic CIDP (CIDP-I) and CIDP with monoclonal gammopathy of uncertain significance (CIDP-MGUS). Patients were examined an average of 28 months after first symptoms. There were several variant presentations that still conformed to the clinical and electrophysiologic definitions of CIDP, including a pure motor syndrome (10%), sensory ataxic variant (12%), mononeuritis multiplex pattern (9%), paraparetic pattern (4%), and relapsing acute Guillain-Barré syndrome (16%). Pain was more frequent than in previous studies (42%). Conduction block was the commonest EMG abnormality (detected in at least one nerve in 73% of patients), but only 31% had a pure demyelinating neuropathy and the majority had some degree of axonal change. Patients with CIDP-MGUS had less severe weakness, greater imbalance, leg ataxia, vibration loss in the hands, and absent median and ulnar sensory potentials, but were as likely as CIDP-I patients to respond to plasma exchange. Seventeen of 44 patients (39%) with idiopathic CIDP improved for at least 2 months with an initial therapy. Although the response rates among plasma exchange, IVIG, and steroids were similar, functional improvement (Rankin score) was greatest with plasma exchange. Of 26 patients who failed to respond to an initial therapy, 9 (35%) benefited from an alternative treatment, and of the 11 who required a third modality 3 (27%) improved. Overall, 66% responded to one of the three main therapies for CIDP.

Nerve root enhancement of the cauda equina occurs in Guillain-Barré syndrome (GBS), but the frequency, diagnostic value, and meaning of this finding is unknown. We prospectively obtained gadolinium-enhanced lumbosacral spine MRIs in 24 consecutive patients with acute GBS and blindly rated nerve root enhancement as absent, mild, or prominent. The MRIs were obtained 13 days, mean, after onset of symptoms (range 2 to 42 days). Twenty of 24 patients had cauda equina nerve root enhancement, which was mild in 6 and prominent in 14. Eighteen of 19 with "typical" GBS had enhancement, compared with 2 of 5 with a variant presentation. Sixty percent of patients with prominent enhancement had severe back or leg pain in contrast to 10% of patients with mild or no enhancement. The GBS disability grade (0 to 5 scale) was higher in patients with prominent enhancement, and significantly fewer patients with prominent nerve root enhancement could walk independently by 2 months. There was no relationship between nerve root enhancement and the timing of the MRI, CSF protein, any of several EMG abnormalities, duration of hospitalization, mean disability grade at 2 months, or the time required for patients to improve to grade 2. In two patients, the EMGs at 11 and 20 days, respectively, were normal except for slightly prolonged F-responses and neurogenic recruitment, but there were prominent nerve root enhancement and an elevated CSF protein. Enhancement of the cauda equina nerve roots with gadolinium on lumbosacral MRI is 83% sensitive of acute GBS and was present in 95% of typical cases. This finding may be useful when electrophysiologic abnormalities are equivocal. In addition, conspicuous nerve root enhancement correlates with pain, GBS disability grade, and duration of recovery.

Objective: To report five stroke patients with sensory deficits including prominent chest discomfort mimicking angina., Background: Chest wall sensory discomfort, as a part of unilateral sensory dysfunction, has seldom been recognized as a potential imitator of cardiac ischemia., Methods: A retrospective review of stroke patients with sensory symptoms from the New England Medical Center Stroke Registry., Results: As a part of an acute stroke that included unilateral sensory symptoms and signs, five patients had chest pain or discomfort, which prompted cardiac evaluation for potential coronary artery disease. In two patients, the primary presentation was chest discomfort. In the other three, chest discomfort was part of a more extensive stroke syndrome. The symptoms were described as "burning," "hot feeling," "flashes," "tightness," and "cold." In three patients, an MRI or CT scan showed an infarct in the thalamus, corona radiata, or lateral medulla. Cardiac evaluation was negative in all but one patient who had single vessel percutaneous transluminal coronary angioplasty without resolution of sensory symptoms. Chest discomfort fluctuated but persisted for months or years after presentation., Conclusion: Chest discomfort mimicking cardiac ischemia may be a prominent sensory symptom in acute stroke.