Publications by authors named "Bart Jacobs"

256 Publications

Pharmacy Compounded Medicines for Patients With Rare Diseases: Lessons Learned From Chenodeoxycholic Acid and Cholic Acid.

Front Pharmacol 2021 28;12:758210. Epub 2021 Sep 28.

Department of Pharmacy and Clinical Pharmacology, University of Amsterdam, Amsterdam, Netherlands.

Patients with rare diseases are often confronted with the fact that effective medicines are unavailable or simply not being developed. This situation jeopardizes the health of a large population of vulnerable patients with rare diseases. Pharmacy compounded formulations can provide a safe alternative when authorized treatments are unavailable or unsuitable. Practical guidelines on how to develop and implement pharmacy compounded formulations for patients with rare diseases are limited. The aim of this article is to provide guidance for when and how to apply pharmacy compounded formulations for patients with rare diseases. This is illustrated with two challenging examples: the development and implementation of pharmacy compounding of 1) chenodeoxycholic acid (CDCA) capsules for patients with cerebrotendinous xanthomatosis (CTX) and 2) cholic acid (CA) capsules for patients with rare bile acid synthesis defects (BASD). All critical steps of the development of CDCA and CA capsules are explained and summarized in a practical guideline.
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http://dx.doi.org/10.3389/fphar.2021.758210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505773PMC
September 2021

[Evidence based guidelines. Diagnosis and management of Guillain-Barré syndrome in ten steps].

Medicina (B Aires) 2021 ;81(5):817-836

Department of Neurology, Erasmus University Medical Center, Rotterdam, The Netherlands.

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 in 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.
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October 2021

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

Brain 2021 Sep 23. Epub 2021 Sep 23.

Department of Neurology, St. Elisabeth-TweeSteden Hospital, 5022 GC, Tilburg, The Netherlands.

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.
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http://dx.doi.org/10.1093/brain/awab279DOI Listing
September 2021

Antecedent infections in Guillain-Barré syndrome in endemic areas of arbovirus transmission: A multinational case-control study.

J Peripher Nerv Syst 2021 Sep 22. Epub 2021 Sep 22.

Department of Neurology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.

Half of the world's population is at risk of arthropod-borne virus (arbovirus) infections. Several arbovirus infections have been associated with Guillain-Barré syndrome (GBS). We investigated whether arboviruses are driving GBS beyond epidemic phases of transmission and studied the antibody response to glycolipids. The protocol of the International Guillain-Barré syndrome Outcome Study (IGOS), an observational prospective cohort study, was adapted to a case-control design. Serum samples were tested for a recent infection with Zika virus (ZIKV), dengue virus (DENV), chikungunya (CHIKV) virus, hepatitis E virus, Epstein-Barr virus (EBV), cytomegalovirus (CMV), Campylobacter jejuni, and Mycoplasma pneumoniae, and for antibodies to glycolipids. Forty-nine patients were included from Brazil (63%), Argentina (14%), and Malaysia (22%). Evidence of a recent infection was found in 27/49 (55%) patients: C jejuni (n = 15, 31%), M pneumoniae (n = 5, 10%), CHIKV (n = 2, 4%), EBV (n = 1, 2%), C jejuni and M pneumoniae (n = 2, 4%), CMV and DENV (n = 1, 2%), and C jejuni and DENV (n = 1, 2%). In 22 patients, 35 paired controls were collected. Odds ratio for recent infections did not significantly differ between cases and controls. No typical anti-ganglioside antibody binding was associated with recent arbovirus infection. We conclude that arbovirus infections occur in GBS patients outside of epidemic viral transmission, although not significantly more than in controls. Broad infection and anti-ganglioside antibody serology are important to establish the most likely pathogenic trigger in GBS patients. Larger studies are necessary to determine the association between arboviruses and GBS.
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http://dx.doi.org/10.1111/jns.12469DOI Listing
September 2021

Ultrasound Diagnosis of Cardiac Arrest in an 81-Year-Old Postoperative Patient.

Chest 2021 Aug;160(2):e233-e236

Department of Cardiovascular Diseases, University Hospitals Leuven, Leuven, Belgium; Department of Cardiac Intensive Care, University Hospitals Leuven, Leuven, Belgium.

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http://dx.doi.org/10.1016/j.chest.2020.07.105DOI Listing
August 2021

Characterization and Clinical Utility of Mutation Detection Using Cell-Free DNA in Patients with Advanced Melanoma.

Cancers (Basel) 2021 Jul 17;13(14). Epub 2021 Jul 17.

Department of Medical Oncology, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), 1090 Brussels, Belgium.

Tissue-based tests for mutation-positive melanoma involve invasive biopsy procedures, and can lead to an erroneous diagnosis when the tumor samples degrade. Herein, we explored a minimally invasive, cell-free deoxyribonucleic acid (cfDNA)-based platform, to retest patients for mutations. This phase 2 study enrolled adult patients with unresectable/metastatic melanoma. A prescreening testing phase evaluated the concordance between a prior tissue-based mutation test result and a subsequent plasma cfDNA-based test result. A treatment phase evaluated the patients who were confirmed as mutation-positive, and were treated with cobimetinib plus vemurafenib. It was found that 35/54 patients (64.8%) with a mutant status by prior tissue test had a positive  mutation with the cfDNA test. Further, 7/118 patients (5.9%) with a wild-type status had a positive  mutation cfDNA test; tissue retests on archival samples confirmed  mutation positivity in 5/7 patients (71.4%). One of these patients received BRAF pathway-targeted therapy (cobimetinib plus vemurafenib), and had progression-free survival commensurate with previous experience. In the overall cobimetinib plus vemurafenib-treated population, 29/36 patients (80.6%) had an objective response. The median progression-free survival was 13.6 months (95% confidence interval, 9.5-16.5). Cell-free DNA-based tests may be a fast and convenient option to identify mutation status in melanoma patients, and help inform treatment decisions.
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http://dx.doi.org/10.3390/cancers13143591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305047PMC
July 2021

Screening for STIs is one of the main drivers of macrolide consumption in PrEP users.

Int J STD AIDS 2021 Jun 17:9564624211025940. Epub 2021 Jun 17.

Department of Clinical Sciences, 37463Institute of Tropical Medicine, Antwerp, Belgium.

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http://dx.doi.org/10.1177/09564624211025940DOI Listing
June 2021

Worse capecitabine treatment outcome in patients with a low skeletal muscle mass is not explained by altered pharmacokinetics.

Cancer Med 2021 07 14;10(14):4781-4789. Epub 2021 Jun 14.

Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam, The Netherlands.

Background: A low skeletal muscle mass (SMM) has been associated with increased toxicity and shorter survival in cancer patients treated with capecitabine, an oral prodrug of 5-fluorouracil (5-FU). Capecitabine and its metabolites are highly water-soluble and, therefore, more likely to distribute to lean tissues. The pharmacokinetics (PK) in patients with a low SMM could be changed, for example, by reaching higher maximum plasma concentrations. In this study, we aimed to examine whether the association between a low SMM and increased toxicity and shorter survival could be explained by altered PK of capecitabine and its metabolites.

Methods: Previously, a population PK model of capecitabine and metabolites in patients with solid tumors was developed. In our analysis, we included patients from this previous analysis for which evaluable abdominal computed tomography (CT)-scans were available. SMM was measured on CT-scans, by single slice evaluation at the third lumbar vertebra, using the Slice-o-Matic software. The previously developed population PK model was extended with SMM as a covariate, to assess the association between SMM and capecitabine and metabolite PK.

Results: PK and SMM data were available from 151 cancer patients with solid tumors. From the included patients, 55% had a low SMM. No relevant relationships were found between SMM and the PK parameters of capecitabine and, the active and toxic metabolite, 5-FU. SMM only correlated with the PK of the, most hydrophilic, but inactive and non-toxic, metabolite α-fluoro-β-alanine (FBAL). Patients with a low SMM had a smaller apparent volume of distribution and lower apparent clearance of FBAL.

Conclusions: No alterations in PK of capecitabine and the active and toxic metabolite 5-FU were observed in patients with a low SMM. Therefore, the previously identified increased toxicity and shorter survival in patients with a low SMM, could not be explained by changes in pharmacokinetic characteristics of capecitabine and metabolites.
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http://dx.doi.org/10.1002/cam4.4038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290233PMC
July 2021

Intravenous immunoglobulin treatment for mild Guillain-Barré syndrome: an international observational study.

J Neurol Neurosurg Psychiatry 2021 Oct 8;92(10):1080-1088. Epub 2021 Jun 8.

Department of Neurology, Erasmus MC, Rotterdam, The Netherlands

Objective: To compare the disease course in patients with mild Guillain-Barré syndrome (GBS) who were treated with intravenous immunoglobulin (IVIg) or supportive care only.

Methods: We selected patients from the prospective observational International GBS Outcome Study (IGOS) who were able to walk independently at study entry (mild GBS), treated with one IVIg course or supportive care. The primary endpoint was the GBS disability score four weeks after study entry, assessed by multivariable ordinal regression analysis.

Results: Of 188 eligible patients, 148 (79%) were treated with IVIg and 40 (21%) with supportive care. The IVIg group was more disabled at baseline. IVIg treatment was not associated with lower GBS disability scores at 4 weeks (adjusted OR (aOR) 1.62, 95% CI 0.63 to 4.13). Nearly all secondary endpoints showed no benefit from IVIg, although the time to regain full muscle strength was shorter (28 vs 56 days, p=0.03) and reported pain at 26 weeks was lower (n=26/121, 22% vs n=12/30, 40%, p=0.04) in the IVIg treated patients. In the subanalysis with persistent mild GBS in the first 2 weeks, the aOR for a lower GBS disability score at 4 weeks was 2.32 (95% CI 0.76 to 7.13). At 1 year, 40% of all patients had residual symptoms.

Conclusion: In patients with mild GBS, one course of IVIg did not improve the overall disease course. The certainty of this conclusion is limited by confounding factors, selection bias and wide confidence limits. Residual symptoms were often present after one year, indicating the need for better treatments in mild GBS.
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http://dx.doi.org/10.1136/jnnp-2020-325815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458059PMC
October 2021

Data Protection Using Polymorphic Pseudonymisation in a Large-Scale Parkinson's Disease Study.

J Parkinsons Dis 2021;11(s1):S19-S25

Interdisciplinary Hub for Security, Privacy and Data Governance, Radboud University, Nijmegen, The Netherlands.

This paper describes an advanced form of pseudonymisation in a large cohort study on Parkinson's disease, called Personalized Parkinson Project (PPP). The study collects various forms of biomedical data of study participants, including data from wearable devices with multiple sensors. The participants are all from the Netherlands, but the data will be usable by research groups worldwide on the basis of a suitable data use agreement. The data are pseudonymised, as required by Europe's General Data Protection Regulation (GDPR). The form of pseudonymisation that is used in this Parkinson project is based on cryptographic techniques and is 'polymorphic': it gives each participating research group its own 'local' pseudonyms. Still, the system is globally consistent, in the sense that if one research group adds data to PPP under its own local pseudonyms, the data become available for other groups under their pseudonyms. The paper gives an overview how this works, without going into the cryptographic details.
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http://dx.doi.org/10.3233/JPD-202431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385496PMC
January 2021

Second intravenous immunoglobulin dose in patients with Guillain-Barré syndrome with poor prognosis (SID-GBS): a double-blind, randomised, placebo-controlled trial.

Lancet Neurol 2021 04 17;20(4):275-283. Epub 2021 Mar 17.

Department of Neurology, Leiden University Medical Center, Leiden, Netherlands.

Background: Treatment with one standard dose (2 g/kg) of intravenous immunoglobulin is insufficient in a proportion of patients with severe Guillain-Barré syndrome. Worldwide, around 25% of patients severely affected with the syndrome are given a second intravenous immunoglobulin dose (SID), although it has not been proven effective. We aimed to investigate whether a SID is effective in patients with Guillain-Barré syndrome with a predicted poor outcome.

Methods: In this randomised, double-blind, placebo-controlled trial (SID-GBS), we included patients (≥12 years) with Guillain-Barré syndrome admitted to one of 59 participating hospitals in the Netherlands. Patients were included on the first day of standard intravenous immunoglobulin treatment (2 g/kg over 5 days). Only patients with a poor prognosis (score of ≥6) according to the modified Erasmus Guillain-Barré syndrome Outcome Score were randomly assigned, via block randomisation stratified by centre, to SID (2 g/kg over 5 days) or to placebo, 7-9 days after inclusion. Patients, outcome adjudicators, monitors, and the steering committee were masked to treatment allocation. The primary outcome measure was the Guillain-Barré syndrome disability score 4 weeks after inclusion. All patients in whom allocated trial medication was started were included in the modified intention-to-treat analysis. This study is registered with the Netherlands Trial Register, NTR 2224/NL2107.

Findings: Between Feb 16, 2010, and June 5, 2018, 327 of 339 patients assessed for eligibility were included. 112 had a poor prognosis. Of those, 93 patients with a poor prognosis were included in the modified intention-to-treat analysis: 49 (53%) received SID and 44 (47%) received placebo. The adjusted common odds ratio for improvement on the Guillain-Barré syndrome disability score at 4 weeks was 1·4 (95% CI 0·6-3·3; p=0·45). Patients given SID had more serious adverse events (35% vs 16% in the first 30 days), including thromboembolic events, than those in the placebo group. Four patients died in the intervention group (13-24 weeks after randomisation).

Interpretation: Our study does not provide evidence that patients with Guillain-Barré syndrome with a poor prognosis benefit from a second intravenous immunoglobulin course; moreover, it entails a risk of serious adverse events. Therefore, a second intravenous immunoglobulin course should not be considered for treatment of Guillain-Barre syndrome because of a poor prognosis. The results indicate the need for treatment trials with other immune modulators in patients severely affected by Guillain-Barré syndrome.

Funding: Prinses Beatrix Spierfonds and Sanquin Plasma Products.
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http://dx.doi.org/10.1016/S1474-4422(20)30494-4DOI Listing
April 2021

Misdiagnosis and diagnostic pitfalls of chronic inflammatory demyelinating polyradiculoneuropathy.

Eur J Neurol 2021 06 9;28(6):2065-2073. Epub 2021 Apr 9.

Department of Neurology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Background And Purpose: The aim of this study was to determine the frequency of over- and underdiagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and to identify related diagnostic pitfalls.

Methods: We conducted a retrospective study in Dutch patients referred to the Erasmus University Medical Centre Rotterdam between 2011 and 2017 with either a diagnosis of CIDP or another diagnosis that was revised to CIDP. We used the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) 2010 diagnostic criteria for CIDP to classify patients into three groups: overdiagnosis, underdiagnosis, or confirmed diagnosis of CIDP. Clinical and laboratory features and treatment history were compared between groups.

Results: A referral diagnosis of CIDP was revised in 32% of patients (31/96; overdiagnosis). Of 81 patients diagnosed with CIDP, 16 (20%) were referred with another diagnosis (underdiagnosis). In the overdiagnosed patients, 20% of muscle weakness was asymmetric, 48% lacked proximal muscle weakness, 29% only had distal muscle weakness, 65% did not fulfil the electrodiagnostic criteria for CIDP, 74% had an elevated cerebrospinal fluid (CSF) protein level, and 97% had another type of neuropathy. In the underdiagnosed patients, all had proximal muscle weakness, 50% had a clinically atypical CIDP, all fulfilled the electrodiagnostic criteria for CIDP, and 25% had an increased CSF protein level.

Conclusion: Over- and underdiagnosis of CIDP is common. Diagnostic pitfalls include lack of attention to proximal muscle weakness as a diagnostic hallmark of CIDP, insufficient recognition of clinical atypical phenotypes, overreliance on CSF protein levels, misinterpretation of nerve conduction studies and poor adherence to electrodiagnostic criteria, and failure to exclude other causes of polyneuropathy.
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http://dx.doi.org/10.1111/ene.14796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252611PMC
June 2021

Guillain-Barré syndrome in low-income and middle-income countries: challenges and prospects.

Nat Rev Neurol 2021 May 1;17(5):285-296. Epub 2021 Mar 1.

Department of Neurology, Erasmus MC, University Medical Center, Rotterdam, Netherlands.

The epidemiology, clinical characteristics, management and outcome of Guillain-Barré syndrome (GBS) differ between low-income and middle-income countries (LMIC) and high-income countries (HIC). At present, limited data are available on GBS in LMIC and the true incidence of GBS in many LMIC remains unknown. Increased understanding of GBS in LMIC is needed because poor hygiene and high exposure to infections render populations in LMIC vulnerable to GBS outbreaks. Furthermore, insufficient diagnostic and health-care facilities in LMIC contribute to delayed diagnosis in patients with severe presentations of GBS. In addition, the lack of national clinical guidelines and absence of affordable, effective treatments contribute to worse outcomes and higher mortality in LMIC than HIC. Systematic population-based surveillance studies, cohort and case-control studies are required to understand the incidence and risk factors for GBS. Novel, targeted and cost-effective treatment strategies need to be developed in the context of health system challenges in LMIC. To ensure integrative rehabilitation services in LMIC, existing prognostic models must be validated, and responsive outcome measures that are cross-culturally applicable must be developed. Therefore, fundamental and applied research to improve the clinical management of GBS in LMIC should become a critical focus of future research programmes.
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http://dx.doi.org/10.1038/s41582-021-00467-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920001PMC
May 2021

Guillain-Barré Syndrome in Suriname; Clinical Presentation and Identification of Preceding Infections.

Front Neurol 2021 10;12:635753. Epub 2021 Feb 10.

Department of Viroscience, Erasmus Medical Center, Rotterdam, Netherlands.

Guillain-Barré syndrome (GBS) is associated with various types of preceding infections including and cytomegalovirus, but there is also an association with arthropod borne viruses (arboviruses), such as Zika virus, that are endemic in tropical regions. Here we present the clinical characteristics of 12 GBS patients from Suriname that were hospitalized between the beginning of 2016 and half 2018. Extensive diagnostic testing was performed for pathogens that are commonly associated with GBS, but also for arboviruses, in order to identify the preceding infection that might have led to GBS. With this extensive testing algorithm, we could identify a recent infection in six patients of which four of them had evidence of a recent Zika virus or dengue virus infection. These results suggest that arboviruses, specifically Zika virus but possibly also dengue virus, might be important causative agents of GBS in Suriname. Furthermore, we found that more accessibility of intravenous immunoglobulins or plasma exchange could improve the treatment of GBS in Suriname.
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http://dx.doi.org/10.3389/fneur.2021.635753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902883PMC
February 2021

Case Report: Therapeutic Threshold for Rifampicin-Resistant Tuberculosis: A Case Report from Maputo, Mozambique.

Am J Trop Med Hyg 2021 Feb 8. Epub 2021 Feb 8.

2Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.

We present a case of a patient in Mozambique, who initiated treatment for rifampicin-resistant tuberculosis (RR-TB) without proof of resistance. For this patient, we estimated the probability of RR-TB using likelihood ratios of clinical arguments. The probability of RR-TB in Mozambique, positive HIV status, and treatment failure after a first treatment and after retreatment were included as confirming arguments, and a rapid molecular test showing rifampicin susceptibility as excluding argument. The therapeutic threshold to start treatment for RR-TB is unknown, but probably lower than 47% and should be calculated to guide clinical decisions.
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http://dx.doi.org/10.4269/ajtmh.20-0959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045612PMC
February 2021

Guillain-Barré Syndrome Outbreak in Peru 2019 Associated With Infection.

Neurol Neuroimmunol Neuroinflamm 2021 03 5;8(2). Epub 2021 Feb 5.

From the Departamento de Medicina (A.P.R., M.A.C., C.C.C., J.A.D., M.A.T., J.T.A., H.F.U.), Servicio de Neurología y Neuropsiquiatría, Hospital Cayetano Heredia, Lima, Perú; Department of Neurology (S.E.L.) and Department of Neurology and Department of Immunology (B.C.J.), Erasmus MC, University Medical Center Rotterdam, Netherlands; Institute of Infection, Immunity and Inflammation (S.K.H., D.G., H.J.W.), University of Glasgow, United Kingdom; Departamento de Enfermedades Infecciosas Tropicales y Dermatológicas (A.L.), Hospital Cayetano Heredia, Lima, Perú; U.S. Naval Medical Research Unit-6 (M.G., M.R., J.D.R., R.M.), Lima, Peru; Center for Computational Biology (D.P., R.M.S., S.L.S.), Department of Computer Science, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD; and Department of Pathology (P.J.S.), Department of Neurology (D.R.C.), and Department of Neurology and Department of Pathology (C.A.P.), Johns Hopkins University School of Medicine, Baltimore, MD.

Objective: To identify the clinical phenotypes and infectious triggers in the 2019 Peruvian Guillain-Barré syndrome (GBS) outbreak.

Methods: We prospectively collected clinical and neurophysiologic data of patients with GBS admitted to a tertiary hospital in Lima, Peru, between May and August 2019. Molecular, immunologic, and microbiological methods were used to identify causative infectious agents. Sera from 41 controls were compared with cases for antibodies to and gangliosides. Genomic analysis was performed on 4 isolates.

Results: The 49 included patients had a median age of 44 years (interquartile range [IQR] 30-54 years), and 28 (57%) were male. Thirty-two (65%) had symptoms of a preceding infection: 24 (49%) diarrhea and 13 (27%) upper respiratory tract infection. The median time between infectious to neurologic symptoms was 3 days (IQR 2-9 days). Eighty percent had a pure motor form of GBS, 21 (43%) had the axonal electrophysiologic subtype, and 18% the demyelinating subtype. Evidence of recent infection was found in 28/43 (65%). No evidence of recent arbovirus infection was found. Twenty-three cases vs 11 controls (OR 3.3, confidence interval [CI] 95% 1.2-9.2, < 0.01) had IgM and/or IgA antibodies against . Anti-GM1:phosphatidylserine and/or anti-GT1a:GM1 heteromeric complex antibodies were strongly positive in cases (92.9% sensitivity and 68.3% specificity). Genomic analysis showed that the strains were closely related and had the Asn51 polymorphism at gene.

Conclusions: Our study indicates that the 2019 Peruvian GBS outbreak was associated with infection and that the strains linked to GBS circulate widely in different parts of the world.
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http://dx.doi.org/10.1212/NXI.0000000000000952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057064PMC
March 2021

Genetic biomarkers for intravenous immunoglobulin response in chronic inflammatory demyelinating polyradiculoneuropathy.

Eur J Neurol 2021 05 6;28(5):1677-1683. Epub 2021 Feb 6.

Department of Immunology, Erasmus MC, University Medical Centre, Rotterdam, the Netherlands.

Background And Purpose: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a clinical and electrophysiological heterogeneous immune-mediated polyneuropathy. Intravenous immunoglobulin (IVIg), corticosteroids, and plasma exchange are proven effective treatments for CIDP. The clinical response to IVIg is variable between patients and currently unexplained. Finding biomarkers related to treatment response can help to understand the diversity of CIDP and personalise treatment choice.

Methods: We investigated whether genetic variation between patients may explain some of these differences in treatment response. Based on previous publications, we selected six candidate genes that might affect immune and axonal functions, IVIg metabolism, and treatment response in CIDP. Genetic variants were assessed in 172 CIDP patients treated with at least one course of IVIg (2 g/kg). A response to IVIg was defined by ≥1 grade improvement on the modified Rankin Scale. Blood samples were tested for variations in CNTN2, PRF1, FCGRT, FCGR2B, GJB1, and SH2D2A genes.

Results: In univariate analysis, patients with the FCGR2B promoter variant 2B.4/2B.1 responded more often to IVIg than patients with the 2B.1/2B.1 variant (odds ratio [OR] = 6.9, 95% confidence interval [CI] = 1.6-30; p = 0.003). Patients with the p.(Ala91Val) variant of PRF1 were less often IVIg responsive (OR = 0.34, 95% CI = 0.13-0.91; p = 0.038). In multivariate analysis, both PRF1 and FCGR2B showed discriminative ability to predict the chance of IVIg response (area under the curve = 0.67).

Conclusions: Variations in PRF1 and the promoter region of FCGR2B are associated with the response to IVIg in CIDP. These findings, which require validation, are a first step towards the understanding of the heterogeneity in the treatment response in CIDP.
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http://dx.doi.org/10.1111/ene.14742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247870PMC
May 2021

Changes in motor nerve excitability in acute phase Guillain-Barré syndrome.

Muscle Nerve 2021 04 2;63(4):546-552. Epub 2021 Feb 2.

Neurology, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Background: The most common subtypes of Guillain-Barré syndrome (GBS) are acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). In the first days after the onset of weakness, standard nerve conduction studies (NCS) may not distinguish GBS subtypes. Reduced nerve excitability may be an early symptom of nerve dysfunction, which can be determined with the compound muscle action potential (CMAP) scan. The aim of this study was to explore whether early changes in motor nerve excitability in GBS patients are related to various subtypes.

Methods: Prospective case-control study in 19 GBS patients from The Netherlands and 22 from Bangladesh. CMAP scans were performed within 2 days of hospital admission and NCS 7-14 days after onset of weakness. CMAP scans were also performed in age- and country-matched controls.

Results: CMAP scan patterns of patients who were classified as AMAN were distinctly different compared to the CMAP scan patterns of the patients who were classified as AIDP. The most pronounced differences were found in the stimulus intensity parameters.

Conclusions: CMAP scans made at hospital admission demonstrate several characteristics that can be used as an early indicator of GBS subtype.
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http://dx.doi.org/10.1002/mus.27172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049016PMC
April 2021

Evaluation of conventional and four real-time PCR methods for the detection of Leishmania on field-collected samples in Ethiopia.

PLoS Negl Trop Dis 2021 01 12;15(1):e0008903. Epub 2021 Jan 12.

Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.

In most low-resource settings, microscopy still is the standard method for diagnosis of cutaneous leishmaniasis, despite its limited sensitivity. In Ethiopia, the more sensitive molecular methods are not yet routinely used. This study compared five PCR methods with microscopy on two sample types collected from patients with a suspected lesion to advise on optimal diagnosis of Leishmania aethiopica. Between May and July 2018, skin scrapings (SS) and blood exudate from the lesion spotted on filter paper (dry blood spot, DBS) were collected for PCR from 111 patients of four zones in Southern Ethiopia. DNA and RNA were simultaneously extracted from both sample types. DNA was evaluated by a conventional PCR targeting ITS-1 and three probe-based real-time PCRs: one targeting the SSU 18S rRNA and two targeting the kDNA minicircle sequence (the 'Mary kDNA PCR' and a newly designed 'LC kDNA PCR' for improved L. aethiopica detection). RNAs were tested with a SYBR Green-based RT-PCR targeting spliced leader (SL) RNA. Giemsa-stained SS smears were examined by microscopy. Of the 111 SS, 100 were positive with at least two methods. Sensitivity of microscopy, ITS PCR, SSU PCR, Mary kDNA PCR, LC kDNA PCR and SL RNA PCR were respectively 52%, 22%, 64%, 99%, 100% and 94%. Microscopy-based parasite load correlated well with real-time PCR Ct-values. Despite suboptimal sample storage for RNA detection, the SL RNA PCR resulted in congruent results with low Ct-values. DBS collected from the same lesion showed lower PCR positivity rates compared to SS. The kDNA PCRs showed excellent performance for diagnosis of L. aethiopica on SS. Lower-cost SL RNA detection can be a complementary high-throughput tool. DBS can be used for PCR in case microscopy is negative, the SS sample can be sent to the referral health facility where kDNA PCR method is available.
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http://dx.doi.org/10.1371/journal.pntd.0008903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802924PMC
January 2021

Population Pharmacokinetics of Intracellular 5-Fluorouridine 5'-Triphosphate and its Relationship with Hand-and-Foot Syndrome in Patients Treated with Capecitabine.

AAPS J 2021 01 8;23(1):23. Epub 2021 Jan 8.

Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.

Capecitabine is an oral pro-drug of 5-fluorouracil. Patients with solid tumours who are treated with capecitabine may develop hand-and-foot syndrome (HFS) as side effect. This might be a result of accumulation of intracellular metabolites. We characterised the pharmacokinetics (PK) of 5-fluorouridine 5'-triphosphate (FUTP) in peripheral blood mononuclear cells (PBMCs) and assessed the relationship between exposure to capecitabine or its metabolites and the development of HFS. Plasma and intracellular capecitabine PK data and ordered categorical HFS data was available. A previously developed model describing the PK of capecitabine and metabolites was extended to describe the intracellular FUTP concentrations. Subsequently, a continuous-time Markov model was developed to describe the development of HFS during treatment with capecitabine. The influences of capecitabine and metabolite concentrations on the development of HFS were evaluated. The PK of intracellular FUTP was described by an one-compartment model with first-order elimination (k was 0.028 h (95% confidence interval 0.022-0.039)) where the FUTP influx rate was proportional to the 5-FU plasma concentrations. The predicted individual intracellular FUTP concentration was identified as a significant predictor for the development and severity of HFS. Simulations demonstrated a clear exposure-response relationship. The intracellular FUTP concentrations were successfully described and a significant relationship between these intracellular concentrations and the development and severity of HFS was identified. This model can be used to simulate future dosing regimens and thereby optimise treatment with capecitabine.
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http://dx.doi.org/10.1208/s12248-020-00533-1DOI Listing
January 2021

Antiglycolipid antibodies in Guillain-Barré and Fisher syndromes: discovery, current status and future perspective.

J Neurol Neurosurg Psychiatry 2021 03 29;92(3):311-318. Epub 2020 Dec 29.

Department of Neurology and Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Guillain-Barré syndrome (GBS) and Fisher syndrome (FS) are acute autoimmune neuropathies, often preceded by an infection. Antiglycolipid antibody titres are frequently elevated in sera from the acute-phase patients. Particularly, IgG anti-GQ1b antibodies are positive in as high as 90% of FS cases and thus useful for diagnosis. The development of animal models of antiglycolipid antibody-mediated neuropathies proved that some of these antibodies are directly involved in the pathogenetic mechanisms by binding to the regions where the respective target glycolipid is specifically localised. Discovery of the presence of the antibodies that specifically recognise a new conformational epitope formed by two different gangliosides (ganglioside complex) in the acute-phase sera of some patients with GBS suggested the carbohydrate-carbohydrate interaction between glycolipids. This finding indicated the need for further research in basic glycobiological science. Antiglycolipid antibodies, in particular antigangliosides antibodies, are mostly detected in acute motor axonal neuropathy type of GBS and in FS, and less frequently in the acute inflammatory demyelinating polyneuropathy (AIDP) type of GBS or in central nervous system (CNS) diseases. In the future, the search for the putative antibodies in AIDP and those that might be present in CNS diseases should continue. In addition, more efficient standardisation of antiglycolipid antibody detection methods and use as biomarkers in daily clinical practice in neurology is needed.
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http://dx.doi.org/10.1136/jnnp-2020-325053DOI Listing
March 2021

Guillain-Barré syndrome during the Zika virus outbreak in Northeast Brazil: An observational cohort study.

J Neurol Sci 2021 01 14;420:117272. Epub 2020 Dec 14.

Department of Neurology, Hospital da Restauração, Recife, Brazil.

Objective: To determine the clinical phenotype of Guillain-Barré syndrome (GBS) after Zika virus (ZIKV) infection, the anti-glycolipid antibody signature, and the role of other circulating arthropod-borne viruses, we describe a cohort of GBS patients identified during ZIKV and chikungunya virus (CHIKV) outbreaks in Northeast Brazil.

Methods: We prospectively recruited GBS patients from a regional neurology center in Northeast Brazil between December 2014 and February 2017. Serum and CSF were tested for ZIKV, CHIKV, and dengue virus (DENV), by RT-PCR and antibodies, and serum was tested for GBS-associated antibodies to glycolipids.

Results: Seventy-one patients were identified. Forty-eight (68%) had laboratory evidence of a recent arbovirus infection; 25 (52%) ZIKV, 8 (17%) CHIKV, 1 (2%) DENV, and 14 (29%) ZIKV and CHIKV. Most patients with a recent arbovirus infection had motor and sensory symptoms (72%), a demyelinating electrophysiological subtype (67%) and a facial palsy (58%). Patients with a recent infection with ZIKV and CHIKV had a longer hospital admission and more frequent mechanical ventilation compared to the other patients. No specific anti-glycolipid antibody signature was identified in association with arbovirus infection, although significant antibody titres to GM1, GalC, LM1, and GalNAc-GD1a were found infrequently.

Conclusion: A large proportion of cases had laboratory evidence of a recent infection with ZIKV or CHIKV, and recent infection with both viruses was found in almost one third of patients. Most patients with a recent arbovirus infection had a sensorimotor, demyelinating GBS. We did not find a specific anti-glycolipid antibody signature in association with arbovirus-related GBS.
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http://dx.doi.org/10.1016/j.jns.2020.117272DOI Listing
January 2021

Chemoenzymatic Synthesis of Lipo-oligosaccharide Core Domains to Examine Guillain-Barré Syndrome Serum Antibody Specificities.

J Am Chem Soc 2020 11 9;142(46):19611-19621. Epub 2020 Nov 9.

Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602-4712, United States.

Guillain-Barré syndrome is often caused by infection that has induced antibodies to the lipo-oligosaccharide (LOS) that cross-react with gangliosides at peripheral nerves causing polyneuropathy. To examine fine specificities of anti-ganglioside antibodies and develop a more robust platform for diagnosis and disease monitoring, we developed a chemoenzymatic approach that provided an unprecedented panel of oligosaccharides composed of the inner-core of the LOS of extended by various ganglioside mimics. The compounds and corresponding ganglio-oligosaccharides were printed as a microarray to examine binding specificities of lectins, anti-ganglioside antibodies, and serum antibodies of GBS patients. Although lectins and anti-ganglioside antibodies did not differentiate the ganglio-oligosaccharides and mimics, the patient serum samples bound much more strongly to the ganglioside mimics. The data indicate that antibodies have been elicited to a foreign epitope that includes a heptosyl residue unique of bacterial LOS and that these antibodies subsequently cross-react with lower affinity to gangliosides. The microarray detected anti-GM1a antibodies with high sensitivity and will be attractive for diagnosis, disease monitoring, and immunological research.
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http://dx.doi.org/10.1021/jacs.0c08583DOI Listing
November 2020

Neurofilament light chain as biomarker for axonal damage in Guillain-Barré syndrome.

Authors:
Bart C Jacobs

J Neurol Neurosurg Psychiatry 2020 Nov 5. Epub 2020 Nov 5.

Neurology and Immunology, Erasmus Medical Center, Rotterdam, The Netherlands

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http://dx.doi.org/10.1136/jnnp-2020-324308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803883PMC
November 2020

Costing of Cesarean Sections in a Government and a Non-Governmental Hospital in Cambodia-A Prerequisite for Efficient and Fair Comprehensive Obstetric Care.

Int J Environ Res Public Health 2020 11 2;17(21). Epub 2020 Nov 2.

Department of General Business Administration and Health Care Management, University of Greifswald, 17489 Greifswald, Germany.

Knowing the cost of health care services is a prerequisite for evidence-based management and decision making. However, only limited costing data is available in many low- and middle-income countries. With a substantially increasing number of facility-based births in Cambodia, costing data for efficient and fair resource allocation is required. This paper evaluates the costs for cesarean section (CS) at a public and a Non-Governmental (NGO) hospital in Cambodia in the year 2018. We performed a full and a marginal cost analysis, i.e., we developed a cost function and calculated the respective unit costs from the provider's perspective. We distinguished fixed, step-fixed, and variable costs and followed an activity-based costing approach. The processes were determined by personal observation of CS-patients and all procedures; the resource consumption was calculated based on the existing accounting documentation, observations, and time-studies. Afterwards, we did a comparative analysis between the two hospitals and performed a sensitivity analysis, i.e., parameters were changed to cater for uncertainty. The public hospital performed 54 monthly CS with an average length of stay (ALOS) of 7.4 days, compared to 18 monthly CS with an ALOS of 3.4 days at the NGO hospital. Staff members at the NGO hospital invest more time per patient. The cost per CS at the current patient numbers is US$470.03 at the public and US$683.23 at the NGO hospital. However, the unit cost at the NGO hospital would be less than at the public hospital if the patient numbers were the same. The study provides detailed costing data to inform decisionmakers and can be seen as a steppingstone for further costing exercises.
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http://dx.doi.org/10.3390/ijerph17218085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663741PMC
November 2020

Cross-border medical travels from Cambodia: pathways to care, associated costs and equity implications.

Health Policy Plan 2020 Oct;35(8):1011-1020

Department of Global Health and Development, London School of Hygiene and Tropical Medicine, London, UK.

In low- and middle-income countries, patients may travel abroad to seek better health services or treatments that are not available at home, especially in regions where great disparities exist between the standard of care in neighbouring countries. While awareness of South-South medical travels has increased, only a few studies investigated this phenomenon in depth from the perspective of sending countries. This article aims to contribute to these studies by reporting findings from a qualitative study of medical travels from Cambodia and associated costs. Data collection primarily involved interviews with Cambodian patients returning from Thailand and Vietnam, conducted in 2017 in the capital Phnom Penh and two provinces, and interviews with key informants in the local health sector. The research findings show that medical travels from Cambodia are driven and shaped by an interplay of socio-economic, cultural and health system factors at different levels, from the effects of regional trade liberalization to perceptions about the quality of care and the pressure of relatives and other advisers in local communities. Furthermore, there is a diversity of medical travels from Cambodia, ranging from first class travels to international hospitals in Bangkok and cross-border 'medical tourism' to perilous overland journeys of poor patients, who regularly resort to borrowing or liquidating assets to cover costs. The implications of the research findings for health sector development and equitable access to care for Cambodians deserve particular attention. To some extent, the increase in medical travels can stimulate improvements in the quality of local health services. However, concerns remain that these developments will mainly affect high-cost private services, widening disparities in access to care between population groups.
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http://dx.doi.org/10.1093/heapol/czaa061DOI Listing
October 2020

Towards a seamful ethics of Covid-19 contact tracing apps?

Ethics Inf Technol 2020 Sep 28:1-11. Epub 2020 Sep 28.

Interdisciplinary Hub for Security, Privacy and Data Governance (iHub), Radboud University, Nijmegen, the Netherlands.

In the early months of 2020, the deadly Covid-19 disease spread rapidly around the world. In response, national and regional governments implemented a range of emergency lockdown measures, curtailing citizens' movements and greatly limiting economic activity. More recently, as restrictions begin to be loosened or lifted entirely, the use of so-called contact tracing apps has figured prominently in many jurisdictions' plans to reopen society. Critics have questioned the utility of such technologies on a number of fronts, both practical and ethical. However, little has been said about the ways in which the normative design choices of app developers, and the products that result therefrom, might contribute to ethical reflection and wider political debate. Drawing from scholarship in critical design and human-computer interaction, this paper examines the development of a QR code-based tracking app called Zwaai ('Wave' in Dutch), where its designers explicitly positioned the app as an alternative to the predominant Bluetooth and GPS-based approaches. Through analyzing these designers' choices, this paper argues that QR code infrastructures can work to surface a set of , two of which are discussed here- and -that more 'seamless' protocols like Bluetooth actively aim to bypass, and which may go otherwise unnoticed by existing ethical frameworks.
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http://dx.doi.org/10.1007/s10676-020-09559-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521862PMC
September 2020

Neurological disease in adults with Zika and chikungunya virus infection in Northeast Brazil: a prospective observational study.

Lancet Neurol 2020 10 16;19(10):826-839. Epub 2020 Sep 16.

National Institute for Health Research Health Protection Research Unit on Emerging and Zoonotic Infections, Institute of Infection, Veterinary & Ecological Sciences, University of Liverpool, Liverpool, UK; The Walton Centre NHS Foundation Trust, Liverpool, UK; Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK. Electronic address:

Background: Since 2015, the arthropod-borne viruses (arboviruses) Zika and chikungunya have spread across the Americas causing outbreaks, accompanied by increases in immune-mediated and infectious neurological disease. The spectrum of neurological manifestations linked to these viruses, and the importance of dual infection, are not known fully. We aimed to investigate whether neurological presentations differed according to the infecting arbovirus, and whether patients with dual infection had a different disease spectrum or severity.

Methods: We report a prospective observational study done during epidemics of Zika and chikungunya viruses in Recife, Pernambuco, a dengue-endemic area of Brazil. We recruited adults aged 18 years or older referred to Hospital da Restauração, a secondary-level and tertiary-level hospital, with suspected acute neurological disease and a history of suspected arboviral infection. We looked for evidence of Zika, chikungunya, or dengue infection by viral RNA or specific IgM antibodies in serum or CSF. We grouped patients according to their arbovirus laboratory diagnosis and then compared demographic and clinical characteristics.

Findings: Between Dec 4, 2014, and Dec 4, 2016, 1410 patients were admitted to the hospital neurology service; 201 (14%) had symptoms consistent with arbovirus infection and sufficient samples for diagnostic testing and were included in the study. The median age was 48 years (IQR 34-60), and 106 (53%) were women. 148 (74%) of 201 patients had laboratory evidence of arboviral infection. 98 (49%) of them had a single viral infection (41 [20%] had Zika, 55 [27%] had chikungunya, and two [1%] had dengue infection), whereas 50 (25%) had evidence of dual infection, mostly with Zika and chikungunya viruses (46 [23%] patients). Patients positive for arbovirus infection presented with a broad range of CNS and peripheral nervous system (PNS) disease. Chikungunya infection was more often associated with CNS disease (26 [47%] of 55 patients with chikungunya infection vs six [15%] of 41 with Zika infection; p=0·0008), especially myelitis (12 [22%] patients). Zika infection was more often associated with PNS disease (26 [63%] of 41 patients with Zika infection vs nine [16%] of 55 with chikungunya infection; p≤0·0001), particularly Guillain-Barré syndrome (25 [61%] patients). Patients with Guillain-Barré syndrome who had Zika and chikungunya dual infection had more aggressive disease, requiring intensive care support and longer hospital stays, than those with mono-infection (median 24 days [IQR 20-30] vs 17 days [10-20]; p=0·0028). Eight (17%) of 46 patients with Zika and chikungunya dual infection had a stroke or transient ischaemic attack, compared with five (6%) of 96 patients with Zika or chikungunya mono-infection (p=0·047).

Interpretation: There is a wide and overlapping spectrum of neurological manifestations caused by Zika or chikungunya mono-infection and by dual infections. The possible increased risk of acute cerebrovascular disease in patients with dual infection merits further investigation.

Funding: Fundação do Amparo a Ciência e Tecnologia de Pernambuco (FACEPE), EU's Horizon 2020 research and innovation programme, National Institute for Health Research.

Translations: For the Portuguese and Spanish translations of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S1474-4422(20)30232-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494308PMC
October 2020

Guillain-Barré syndrome in SARS-CoV-2 infection: an instant systematic review of the first six months of pandemic.

J Neurol Neurosurg Psychiatry 2020 10 27;91(10):1105-1110. Epub 2020 Aug 27.

Departments of Neurology and Immunology, Erasmus MC, Rotterdam, The Netherlands.

A systematic review from 1 January to 30 June 2020 revealed 42 patients with Guillain-Barré syndrome (GBS) associated with SARS-CoV-2 infection. Single cases and small series were reported from 13 countries, the majority from Europe (79.4%) and especially from Italy (30.9%). SARS-CoV-2 infection was demonstrated by nasopharyngeal swab (85.7%) and serology (14.3%). Median time between COVID-19 and GBS onset in 36 patients was 11.5 days (IQR: 7.7-16). The most common clinical features were: limb weakness (76.2%), hypoareflexia (80.9 %), sensory disturbances (66.7 %) and facial palsy (38.1%). Dysautonomia occurred in 19%, respiratory failure in 33.3% and 40.5% of patients were admitted in intensive care unit. Most patients (71.4%) had the classical clinical presentation but virtually all GBS variants and subtypes were reported. Cerebrospinal fluid (CSF) albumin-cytological dissociation was found in 28/36 (77.8%) and PCR for SARS-CoV-2 was negative in 25/25 patients. Electrodiagnosis was demyelinating in 80.5% and levels 1 and 2 of Brighton criteria of diagnostic certainty, when applicable, were fulfilled in 94.5% patients. Antiganglioside antibodies were positive in only 1/22 patients. Treatments were intravenous immunoglobulin and/or plasma exchange (92.8%) with, at short-time follow-up, definite improvement or recovery in 62.1% of patients. One patient died. In conclusion, the most frequent phenotype of GBS in SARS-CoV-2 infection is the classical sensorimotor demyelinating GBS responding to the usual treatments. The time interval between infectious and neuropathic symptoms, absence of CSF pleocytosis and negative PCR support a postinfectious mechanism. The abundance of reports suggests a pathogenic link between SARS-CoV-2 infection and GBS but a case-control study is greatly needed.
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http://dx.doi.org/10.1136/jnnp-2020-324491DOI Listing
October 2020
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