In 2016, we have seen a rapid emergence of Zika virus-associated Guillain-Barré syndrome (GBS) since its first description in a French-Polynesian patient in 2014. Current evidence estimates the ...incidence of GBS at 24 cases per 100 000 persons infected by Zika virus. This will result in a sharp rise in the number of GBS cases worldwide with the anticipated global spread of Zika virus. A better understanding of the pathogenesis of Zika-associated GBS is crucial to prepare us for the current epidemic. In this review, we evaluate the existing literature on GBS in association with Zika and other flavivirus to better define its clinical subtypes and electrophysiological characteristics, demonstrating a demyelinating subtype of GBS in most cases. We also recommend measures that will help reduce the gaps in knowledge that currently exist.
Highlights • Up to 38% of Guillain-Barré syndrome patients change electrodiagnostic classification after serial studies. • To optimize electrodiagnosis at first study we employed three different ...criteria sets and sparse linear discriminant analysis (LDA). • Sparse LDA showed the highest electrodiagnostic accuracy and should be introduced in practice.
Guillain-Barré syndrome (GBS) is a rare, but potentially fatal, immune-mediated disease of the peripheral nerves and nerve roots that is usually triggered by infections. The incidence of GBS can ...therefore increase during outbreaks of infectious diseases, as was seen during the Zika virus epidemics in 2013 in French Polynesia and 2015 in Latin America. Diagnosis and management of GBS can be complicated as its clinical presentation and disease course are heterogeneous, and no international clinical guidelines are currently available. To support clinicians, especially in the context of an outbreak, we have developed a globally applicable guideline for the diagnosis and management of GBS. The guideline is based on current literature and expert consensus, and has a ten-step structure to facilitate its use in clinical practice. We first provide an introduction to the diagnostic criteria, clinical variants and differential diagnoses of GBS. The ten steps then cover early recognition and diagnosis of GBS, admission to the intensive care unit, treatment indication and selection, monitoring and treatment of disease progression, prediction of clinical course and outcome, and management of complications and sequelae.
Signaling through the store-operated Ca2+ release-activated Ca2+ (CRAC) channel regulates critical cellular functions, including gene expression, cell growth and differentiation, and Ca2+ ...homeostasis. Loss-of-function mutations in the CRAC channel pore-forming protein ORAI1 or the Ca2+ sensing protein stromal interaction molecule 1 (STIM1) result in severe immune dysfunction and nonprogressive myopathy. Here, we identify gain-of-function mutations in the cytoplasmic domain of STIM1 (p.R304W) associated with thrombocytopenia, bleeding diathesis, miosis, and tubular myopathy in patients with Stormorken syndrome, and in ORAI1 (p.P245L), associated with a Stormorken-like syndrome of congenital miosis and tubular aggregate myopathy but without hematological abnormalities. Heterologous expression of STIM1 p.R304W results in constitutive activation of the CRAC channel in vitro, and spontaneous bleeding accompanied by reduced numbers of thrombocytes in zebrafish embryos, recapitulating key aspects of Stormorken syndrome. p.P245L in ORAI1 does not make a constitutively active CRAC channel, but suppresses the slow Ca2+-dependent inactivation of the CRAC channel, thus also functioning as a gain-of-function mutation. These data expand our understanding of the phenotypic spectrum of dysregulated CRAC channel signaling, advance our knowledge of the molecular function of the CRAC channel, and suggest new therapies aiming at attenuating store-operated Ca2+ entry in the treatment of patients with Stormorken syndrome and related pathologic conditions.
: Studies have suggested that, by applying certain nerve ultrasound scores, demyelinating and axonal polyneuropathies can be differentiated. In the current study, we investigated the utility of ...ultrasound pattern sub-score A (UPSA) and intra- and internerve cross-sectional area (CSA) variability in the diagnostic evaluation of demyelinating neuropathies.
: Nerve ultrasound was performed in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and acute inflammatory demyelinating polyneuropathy (AIDP) and compared to patients with axonal neuropathies. The UPSA, i.e., the sum of ultrasound scores at eight predefined measurement points in the median (forearm, elbow and mid-arm), ulnar (forearm and mid-arm), tibial (popliteal fossa and ankle) and fibular (lateral popliteal fossa) nerves, was applied. Intra- and internerve CSA variability were defined as maximal CSA/minimal CSA for each nerve and each subject, respectively.
: A total of 34 CIDP, 15 AIDP and 16 axonal neuropathies (including eight axonal Guillain-Barré syndrome (GBS), four hereditary transthyretin amyloidosis, three diabetic polyneuropathy and one vasculitic neuropathy) were included. A total of 30 age- and sex-matched healthy controls were recruited for comparison. Significantly enlarged nerve CSA was observed in CIDP and AIDP with significantly higher UPSA in CIDP compared to the other groups (9.9 ± 2.9 vs. 5.9 ± 2.0 vs. 4.6 ± 1.9 in AIDP vs. axonal neuropathies,
< 0.001). A total of 89.3% of the patients with CIDP had an UPSA score ≥7 compared to the patients with AIDP (33.3%) and axonal neuropathies (25.0%) (
< 0.001). Using this cut-off, the performance of UPSA in differentiating CIDP from other neuropathies including AIDP was excellent (area under the curve of 0.943) with high sensitivity (89.3%), specificity (85.2%) and positive predictive value (73.5%). There were no significant differences in intra- and internerve CSA variability between the three groups.
: The UPSA ultrasound score was useful in distinguishing CIDP from other neuropathies compared to nerve CSA alone.
Highlights ► The existing electrodiagnostic criteria in Guillain–Barré syndrome are unreliable when applied at the initial stages of disease onset. ► Nerve conduction studies performed at two time ...courses, within 2 weeks and 3–8 weeks, may better reflect the final electrodiagnosis of Guillain–Barré syndrome. ► The pattern of recovery in Guillain–Barré syndrome is heterogeneous and validation of the current Erasmus Guillain–Barré syndrome outcome score in different patient populations is required.
There is increasing evidence that the anterior visual pathways are involved in neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD). This study ...investigated longitudinal changes in retinal nerve fiber layer (RNFL) thickness in patients with ALS and PD with the aim of better understanding their roles as biomarkers of disease progression.
This study recruited 21 ALS patients, 19 age-matched PD patients, and 21 agematched healthy controls. Patient demographics and clinical scores relating to the respective diseases were documented. The RNFL thickness was measured using optical coherence tomography at baseline and after 6 months.
At baseline, the RNFL in the superior quadrant was significantly thinner in the patients with ALS than in healthy controls (109.90±22.41 µm vs. 127.81±17.05 µm mean±standard deviation,
=0.008). The RNFL thickness did not differ significantly between the ALS and PD patients or between the PD patients and healthy controls. At 6 months, there was further significant RNFL thinning in patients with ALS, for both the overall thickness (baseline: median=94.5 µm, range=83.0-106.0 µm; follow-up: median=93.5 µm, range=82.5-104.5 µm,
=0.043) and the thickness in the inferior quadrant (median=126 µm, range=109.5-142.5 µm; and median=117.5 µm, range=98.5-136.5 µm; respectively,
=0.032). However, these changes were not correlated with the ALS functional scores. In contrast, the patients with PD did not demonstrate a significant change in RNFL thickness between the two time points.
The RNFL thickness is a promising biomarker of disease progression in patients with ALS but not in those with PD, which has a slower disease progression.
•The current model is simple and can predict AIDP based on NCS done within 8 weeks.•Median MCV, ulnar DML and sural sparing were independently associated with AIDP.•The positive predictive values ...were comparable to other single study criteria.
We aimed to develop a model that can predict the probabilities of acute inflammatory demyelinating polyneuropathy (AIDP) based on nerve conduction studies (NCS) done within eight weeks.
The derivation cohort included 90 Malaysian GBS patients with two sets of NCS performed early (1–20days) and late (3–8 weeks). Potential predictors of AIDP were considered in univariate and multivariate logistic regression models to develop a predictive model. The model was externally validated in 102 Japanese GBS patients.
Median motor conduction velocity (MCV), ulnar distal motor latency (DML) and abnormal ulnar/normal sural pattern were independently associated with AIDP at both timepoints (median MCV: p = 0.038, p = 0.014; ulnar DML: p = 0.002, p = 0.003; sural sparing: p = 0.033, p = 0.009). There was good discrimination of AIDP (area under the curve (AUC) 0.86–0.89) and this was valid in the validation cohort (AUC 0.74–0.94). Scores ranged from 0 to 6, and corresponded to AIDP probabilities of 15–98% at early NCS and 6–100% at late NCS.
The probabilities of AIDP could be reliably predicted based on median MCV, ulnar DML and ulnar/sural sparing pattern that were determined at early and late stages of GBS.
A simple and valid model was developed which can accurately predict the probability of AIDP.
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