Stephan Goedee - Academia.edu (original) (raw)

Papers by Stephan Goedee

Research paper thumbnail of Primary SARS-CoV-2 infection in patients with immune-mediated inflammatory diseases: long-term humoral immune responses and effects on disease activity

BMC Infectious Diseases, May 17, 2023

Background Patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressants (ISP... more Background Patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressants (ISPs) may have impaired long-term humoral immune responses and increased disease activity after SARS-CoV-2 infection. We aimed to investigate long-term humoral immune responses against SARS-CoV-2 and increased disease activity after a primary SARS-CoV-2 infection in unvaccinated IMID patients on ISPs. Methods IMID patients on active treatment with ISPs and controls (i.e. IMID patients not on ISP and healthy controls) with a confirmed SARS-CoV-2 infection before first vaccination were included from an ongoing prospective cohort study (T2B! study). Clinical data on infections and increased disease activity were registered using electronic surveys and health records. A serum sample was collected before first vaccination to measure SARS-CoV-2 anti-receptor-binding domain (RBD) antibodies.

Research paper thumbnail of Nerve ultrasound and magnetic resonance imaging in the diagnosis of neuropathy

Current Opinion in Neurology, Oct 1, 2018

Purpose of review This review summarizes the most relevant developments in the fields of nerve ul... more Purpose of review This review summarizes the most relevant developments in the fields of nerve ultrasound and MRI in the diagnosis of treatable inflammatory neuropathies over the last 18 months. Recent findings MRI and nerve ultrasound can accurately identify potentially treatable neuropathies and thereby help to improve diagnosis. Advanced MRI techniques also show potential to dissect pathophysiology. The apparent mismatch between nerve function and morphology is not surprising and reflects different dimensions of the disease process in neuropathies. Summary MRI and nerve ultrasound have become useful tools in the diagnosis of inflammatory neuropathies.

Research paper thumbnail of High-resolution ultrasound in diagnosis of polyneuropathies

Research paper thumbnail of Randomized double-blind placebo-controlled crossover trial with pyridostigmine in spinal muscular atrophy types 2–4

Brain communications, Dec 9, 2022

Supplementary Table 1. CONSORT Checklist CONSORT 2010 checklist of information to include when re... more Supplementary Table 1. CONSORT Checklist CONSORT 2010 checklist of information to include when reporting a randomised trial* Section/Topic Item No Checklist item Reported on page No Title and abstract 1a Identification as a randomised trial in the title 1 1b Structured summary of trial design, methods, results, and conclusions (for specific guidance see CONSORT for abstracts) 1

Research paper thumbnail of Motor unit integrity in multifocal motor neuropathy: A systematic evaluation with <scp>CMAP</scp> scans

Muscle & Nerve, Dec 16, 2021

Introduction/AimsProgressive axonal loss in multifocal motor neuropathy (MMN) is often assessed w... more Introduction/AimsProgressive axonal loss in multifocal motor neuropathy (MMN) is often assessed with nerve conduction studies (NCS), by recording maximum compound muscle action potentials (CMAPs). However, reinnervation maintains the CMAP amplitude until a significant portion of the motor unit (MU) pool is lost. Therefore, we performed more informative CMAP scans to study MU characteristics in a large cohort of patients with MMN.MethodsWe derived the maximum CMAP amplitude (CMAPmax), an MU number estimate (MUNE), and the largest MU amplitude stimulus current required to elicit 5%, 50%, and 95% of CMAPmax (S5, S50, S95) and relative ranges ([S95 − S5] × 100 / S50) from the scans. These metrics were compared with clinical, laboratory, and NCS results.ResultsForty MMN patients and 24 healthy controls were included in the study. CMAPmax and MUNE were reduced in MMN patients (both P < .001). Largest MU amplitude as a percentage of CMAPmax was increased in MMN patients (P < .001). Disease duration and treatment duration were not associated with MUNE. Relative range was larger in patients with anti‐GM1 antibodies than in those without anti‐GM1 antibodies (P = .016) and controls (P < .001). The largest MU amplitudes were larger in patients without anti‐GM1 antibodies than in patients with anti‐GM1 antibodies (P = .037) and controls (P = .044).DiscussionWe found that MU loss is common in MMN and accompanied by enlarged MUs. Presence of anti‐GM1 antibodies was associated with increased relative range of MU thresholds and reduction in largest MU amplitude. Our findings indicate that CMAP scans complement routine NCS, and may have potential for practical monitoring of treatment efficacy and disease progression.

Research paper thumbnail of Diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy in clinical practice: A survey among Dutch neurologists

Journal of The Peripheral Nervous System, Jul 9, 2020

The diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) i... more The diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is often a challenge. The clinical presentation is diverse, accurate biomarkers are lacking, and the best strategy to initiate and maintain treatment is unclear. The aim of this study was to determine how neurologists diagnose and treat CIDP. We conducted a cross-sectional survey on diagnostic and treatment practices among Dutch neurologists involved in the clinical care of CIDP patients. Forty-four neurologists completed the survey (44/71; 62%). The respondents indicated to use the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) 2010 CIDP guideline for the diagnosis in 77% and for treatment in 50%. Only 57% of respondents indicated that the presence of demyelinating electrophysiological findings was mandatory to confirm the diagnosis of CIDP. Most neurologists used intravenous immunoglobulins (IVIg) as first choice treatment, but the indications to start, optimize, or withdraw IVIg, and the use of other immune-modulatory therapies varied. University-affiliated respondents used the EFNS/PNS 2010 diagnostic criteria, nerve imaging tools, and immunosuppressive drugs more often. Despite the existence of an international guideline, there is considerable variation among neurologists in the strategies employed to diagnose and treat CIDP. More specific recommendations regarding: (a) the minimal set of electrophysiological requirements to diagnose CIDP, (b) the possible added value of nerve imaging, especially in patients not meeting the electrodiagnostic criteria, (c) the most relevant serological examinations, and (d) the clear treatment advice, in the new EFNS/PNS guideline, would likely support its implementation in clinical practice.

Research paper thumbnail of Value and pitfalls of imaging and electrodiagnosis in neurogenic thoracic outlet syndrome: Lessons learned from present and past

Muscle & Nerve, Oct 21, 2021

See article on pages 34–42 in this issue.

Research paper thumbnail of Thoracic outlet syndrome (TROTS) registry: A study protocol for the primary upper extremity deep venous thrombosis section

PLOS ONE, Jan 6, 2023

Introduction There is a lack of comprehensive and uniform data on primary upper extremity deep ve... more Introduction There is a lack of comprehensive and uniform data on primary upper extremity deep venous thrombosis (pUEDVT). pUEDVT includes venous thoracic outlet syndrome related upper extremity deep venous thrombosis (UEDVT) and idiopathic UEDVT. Research on these conditions has been hampered by their rarity, lack of uniform diagnostic criteria, and heterogeneity in therapeutic strategies. To improve current research data collection using input of all various pUEDVT treating medical specialists, we initiated the ThoRacic OuTlet Syndrome (TROTS) registry. The aim of the TROTS registry is to a) collect extensive data on all pUEDVT patients through a predefined protocol, b) give insight in the long term outcome using patient reported outcome measures, c) create guidance in the diagnostic and clinical management of these conditions, and thereby d) help provide content for future research. Methods and analysis The TROTS registry was designed as an international prospective longitudinal observational registry for data collection on pUEDVT patients. All pUEDVT patients, regardless of treatment received, can be included in the registry after informed consent is obtained. All relevant data regarding the initial presentation, diagnostics, treatment, and follow-up will be collected prospectively in an electronic case report form. In addition, a survey containing general questions, a Health-related Quality of Life questionnaire (EQ-5D-5L), and Functional Disability questionnaire (Quick-DASH) will be sent periodically (at the time of inclusion, one and two years after inclusion, and every five years after inclusion) to the participant. The registry protocol was approved by the Medical Ethical Review Board and registered in the Netherlands Trial Register under Trial-ID NL9680. The data generated by

Research paper thumbnail of MRI shows thickening and altered diffusion in the median and ulnar nerves in multifocal motor neuropathy

European Radiology, Sep 21, 2016

Objectives To study disease mechanisms in multifocal motor neuropathy (MMN) with magnetic resonan... more Objectives To study disease mechanisms in multifocal motor neuropathy (MMN) with magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) of the median and ulnar nerves. Methods We enrolled ten MMN patients, ten patients with amyotrophic lateral sclerosis (ALS) and ten healthy controls (HCs). Patients underwent MRI (in a prone position) and nerve conduction studies. DTI and fat-suppressed T2-weighted scans of the forearms were performed on a 3.0T MRI scanner. Fibre tractography of the median and ulnar nerves was performed to extract diffusion parameters: fractional anisotropy (FA), mean (MD), axial (AD) and radial (RD) diffusivity. Cross-sectional areas (CSA) were measured on T2-weighted scans. Results Forty-five out of 60 arms were included in the analysis. AD was significantly lower in MMN patients (2.20 ± 0.12 × 10-3 mm 2 /s) compared to ALS patients (2.31 ± 0.17 × 10-3 mm 2 /s; p < 0.05) and HCs (2.31 ± 0.17 × 10-3 mm 2 /s; p < 0.05). Segmental analysis showed significant restriction of AD, RD and MD (p < 0.005) in the proximal third of the nerves. CSA was significantly larger in MMN patients compared to ALS patients and HCs (p < 0.01). Conclusions Thickening of nerves is compatible with changes in the myelin sheath structure, whereas lowered AD values suggest axonal dysfunction. These findings suggest that myelin and axons are diffusely involved in MMN pathogenesis. Key Points • Diffusion magnetic resonance imaging provides quantitative information about multifocal motor neuropathy (MMN). • Diffusion tensor imaging allows non-invasive evaluation of the forearm nerves in MMN. • Nerve thickening and lowered diffusion parameters suggests myelin and axonal changes. • This study can help to provide insight into pathological mechanisms of MMN.

Research paper thumbnail of Sonomorphology of median nerve in relation to function: Important lessons from carpal tunnel but still complex

Clinical Neurophysiology Practice, 2023

Research paper thumbnail of The relation between nerve morphology detected by sonography and electrodiagnostic findings

Clinical Neurophysiology, Jul 1, 2014

Fig. 1. The figure shows a model of different types of mononeuropathies in relation to the presen... more Fig. 1. The figure shows a model of different types of mononeuropathies in relation to the presence and severity of loss of motor or sensory loss (clinically or by electrodiagnostic testing), time and severity of nerve enlargement detected by HRUS.

Research paper thumbnail of Ultrasound scanning in the diagnosis of peripheral neuropathies

Practical Neurology, Feb 4, 2021

Nerve ultrasound scanning has become a valuable diagnostic tool in the routine workup of peripher... more Nerve ultrasound scanning has become a valuable diagnostic tool in the routine workup of peripheral nerve disorders, effectively complementing conventional electrodiagnostic studies. The most relevant sonographic features are nerve size and structural integrity. Several peripheral neuropathies show characteristic and distinct patterns of nerve enlargement, allowing their early and accurate identification, and reducing test-burden and diagnostic delay for patients. In mononeuropathies such as carpal tunnel syndrome and ulnar neuropathy at the elbow, nerve enlargement develops only at specific sites of entrapment, while in polyneuropathy the nerve enlargement may be multifocal, regional or even diffuse. Nerve ultrasound scanning can reliably identify chronic inflammatory neuropathies, even when extensive electrodiagnostic studies fail, and it should therefore be embedded in routine diagnostic workup of peripheral neuropathies. In this paper we describe a potential diagnostic strategy to achieve this.

Research paper thumbnail of The use and misuse of sonographic reference values in neuromuscular disease

Muscle & Nerve, Apr 27, 2023

Research paper thumbnail of Correlates of Fatigability in Patients With Spinal Muscular Atrophy

Neurology, Nov 20, 2020

Disclosure Statement Bart Bartels obtained research grants from Prinses Beatrix Spierfonds and St... more Disclosure Statement Bart Bartels obtained research grants from Prinses Beatrix Spierfonds and Stichting Spieren voor Spieren, both non-profit foundations. His employer receives fees for SMA-related consultancy activities Janke F. de Groot reports no disclosure Laura E. Habets reports no disclosure Fay-Lynn Asselman reports no disclosure Rense I. Wadman obtained research grant from Stichting Spieren voor Spieren, a non-profit foundation. Edward E. S. Nieuwenhuis reports no disclosure Ruben P.A. van Eijk reports no disclosure H. Stephan Goedee obtained research grants from Prinses Beatrix Spierfonds, a non-profit foundation and received travel grants and speaker fees from Shire/Takeda. W. Ludo van der Pol obtained research grants from Prinses Beatrix Spierfonds and Stichting Spieren voor Spieren, both non-profit foundations. His employer receives fees for SMA-related consultancy activities

Research paper thumbnail of Nerve ultrasound

Neurology, Dec 28, 2018

ObjectiveTo determine interobserver variability of nerve ultrasound in peripheral neuropathy in a... more ObjectiveTo determine interobserver variability of nerve ultrasound in peripheral neuropathy in a prospective, systematic, multicenter study.MethodsWe enrolled 20 patients with an acquired chronic demyelinating or axonal polyneuropathy and 10 healthy controls in 3 different centers. All participants underwent an extensive nerve ultrasound protocol, including cross-sectional area measurements of median, ulnar, fibular, tibial, and sural nerves, and brachial plexus. Real-time image acquisition was performed blind by a local and a visiting investigator (reference). Five patients were investigated using different types of sonographic devices. Intraclass correlation coefficients were calculated, and a random-effects model was fitted to identify factors with significant effect on interobserver variability.ResultsSystematic differences between measurements made by different investigators were small (mean difference 0.11 mm2 [95% confidence interval 0.00–0.23 mm2]). Intraclass correlation coefficients were generally higher in arm nerves (0.48–0.96) than leg nerves (0.46–0.61). The hospital site and sonographic device did not contribute significantly to interobserver variability in the random-effects model.ConclusionsInterobserver variability of nerve ultrasound in peripheral neuropathy is generally limited, especially in arm nerves. Different devices and a multicenter setting have no effect on interobserver variability. Therefore, nerve ultrasound is a reproducible tool for diagnostics in routine clinical practice and (multicenter) research.

Research paper thumbnail of Diagnostic accuracy of MRI and ultrasound in chronic immune-mediated neuropathies

Neurology, Dec 11, 2019

Objective To assess and compare the diagnostic performance of qualitative and (semi-)quantitative... more Objective To assess and compare the diagnostic performance of qualitative and (semi-)quantitative MRI and ultrasound for distinguishing chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN) from segmental spinal muscular atrophy (sSMA). Methods Patients with CIDP (n = 13), MMN (n = 10), or sSMA (n = 12) and healthy volunteers (n = 30) were included. MRI of the brachial plexus, using short tau inversion recovery (STIR), nervespecific T2-weighted (magnetic resonance neurography [MRN]), and diffusion tensor imaging (DTI) sequences, was evaluated. Furthermore, with ultrasound, cross-sectional areas of the nerves were evaluated. Three radiologists blinded for diagnosis qualitatively scored hypertrophy and increased signal intensity (STIR and MRN), and intraobserver and interobserver agreement was assessed. For the (semi-)quantitative modalities, group differences and receiver operator characteristics were calculated. Results Hypertrophy and increased signal intensity were found in all groups including healthy controls. Intraobserver and interobserver agreements varied considerably (intraclass correlation coefficients 0.00-0.811 and 0.101-0.491, respectively). DTI showed significant differences (p < 0.05) among CIDP, MMN, sSMA, and controls for fractional anisotropy, axial diffusivity, and radial diffusivity in the brachial plexus. Ultrasound showed significant differences in crosssectional area (p < 0.05) among CIDP, MMN, and sSMA in upper arm and brachial plexus. For distinguishing immune-mediated neuropathies (CIDP and MMN) from sSMA, ultrasound yielded the highest area under the curve (0.870). Conclusion Qualitative assessment of hypertrophy and signal hyperintensity on STIR or MRN is of limited value. DTI measures may discriminate among CIDP, MMN, and sSMA. Currently, ultrasound may be the most appropriate diagnostic imaging aid in the clinical setting.

Research paper thumbnail of To treat or not to treat mild Guillain-Barré syndrome: limited evidence for but still none against

Journal of Neurology, Neurosurgery, and Psychiatry, Jun 8, 2021

There are several caveats to the use of terminology ‘mild GuillainBarré syndrome (GBS)’ in clinic... more There are several caveats to the use of terminology ‘mild GuillainBarré syndrome (GBS)’ in clinical settings, as this is at present mainly based on motor function of legs and does not include weakness of arms nor other disabling dysfunctions such as ataxia. Moreover, some patients may progress beyond mild, but accurate biomarkers to timely identify this subset are lacking. Corroborating with the shift to less conservative ischaemic stroke treatment, where progression is no longer awaited and disabling symptoms such as exclusively aphasia may be considered appropriate thresholds for treatment with intravenous alteplase, the ‘inflammatory penumbra’ in GBS could be considered to benefit from timely and appropriate treatment (figure 1). In practice, treatment of GBS will often not be delayed when progression is suspected clinically, or dysfunction is still considered sufficiently disabling. Nevertheless, treatment of mild GBS remains a difficult decision in clinical practice. Only plasma exchange (PE) has been studied in this setting with a single randomised controlled trial. This trial performed over two decades ago, showed the benefit of two PE sessions in subjects with GBS still able to walk, in shortening time of onset of motor recovery. No trials of intravenous immunoglobulins (Ig) have been performed in mild GBS, but equivalence of PE and intravenous Ig is generally assumed, supported by data from five comparative studies. Hence, intravenous Ig is often used in this setting, mainly for practical reasons (ie, access route and availability of PE service) (figure 1). Verboon reports the findings of an analysis on a multicentre observational study from a sample of patients with mild GBS, derived from the prospective observational international GBS outcome study, and defined as being able to walk independently, comparing treated with intravenous Ig with receiving supportive care only. The effect of intravenous Ig was evaluated at 4 and 26 weeks by the GBS disability scale. However, floor effect hampered responsiveness as the maximal range of change on this scale was only two points with mild GBS already at lower end. Corrections were performed for a number of known prognostic factors, as well as for early improvement. After one course of intravenous Ig, no differences on GBS disability score were detected at 4 (primary endpoint) and 26 weeks (first secondary endpoint). However, the lack of response on GBS disability scale does not necessarily imply no effect, but may also indicate inaccuracy of this outcome measure to detect smaller changes that could still be clinically relevant. Of note, the time needed to reach full muscle strength was shortened in the intravenous Igtreated group from 56 to 28 days (p=0.03). Pain was otherwise less common in the intravenous Igtreated group at 26 weeks (22% vs 40%, p=0.04). In summary, both intravenous Ig and PE may shorten

Research paper thumbnail of MRI of the intraspinal nerve roots in patients with chronic inflammatory neuropathies: abnormalities correlate with clinical phenotypes

Journal of Neurology, Jan 6, 2022

Chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN) ar... more Chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN) are caused by inflammatory changes of peripheral nerves. It is unknown if the intra-spinal roots are also affected. This MRI study systematically visualized intra-spinal nerve roots, i.e., the ventral and dorsal roots, in patients with CIDP, MMN and motor neuron disease (MND). We performed a cross-sectional study in 40 patients with CIDP, 27 with MMN and 34 with MND. All patients underwent an MRI scan of the cervical intra-spinal roots. We systematically measured intra-spinal nerve root sizes bilaterally in the transversal plane at C5, C6 and C7 level. We calculated mean nerve root sizes and compared them between study groups and between different clinical phenotypes using a univariate general linear model. Patients with MMN and CIDP with a motor phenotype had thicker ventral roots compared to patients with CIDP with a sensorimotor phenotype (p = 0.012), while patients with CIDP with a sensory phenotype had thicker dorsal roots compared to patients with a sensorimotor phenotype (p = 0.001) and with MND (p = 0.004). We here show changes in the morphology of intra-spinal nerve roots in patients with chronic inflammatory neuropathies, compatible with their clinical phenotype.

Research paper thumbnail of High-resolution mapping identifies HLA class II associations with multifocal motor neuropathy

Neurobiology of Aging, May 1, 2021

OBJECTIVE To gain further insight in the immunopathology underlying multifocal motor neuropathy (... more OBJECTIVE To gain further insight in the immunopathology underlying multifocal motor neuropathy (MMN) by exploring the association between MMN and the human leukocyte antigen (HLA) class II DRB1, DQB1, and DQA loci in depth and by correlating associated haplotypes to detailed clinical and anti-ganglioside antibody data. METHODS We performed high-resolution HLA-class II typing for the DRB1, DQB1, and DQA1 loci in 126 well-characterized MMN patients and assessed disease associations with haplotypes. We used a cohort of 1305 random individuals as a reference for haplotype distribution in the Dutch population. RESULTS The DRB1*15:01-DQB1*06:02 haplotype (OR 1.6 [95% CI 1.1-2.2], p < 0.05) and the DRB1*12:01-DQB1*03:01 haplotype (OR 2.7 [95% CI 1.2-5.5], p < 0.05) were more frequent in patients with MMN than in controls. These haplotypes were not associated with disease course, response to treatment or anti-ganglioside antibodies. CONCLUSIONS MMN is associated with the DRB1*15:01-DQB1*06:02 and DRB1*12:01-DQB1*03:01 haplotypes. These HLA molecules or gene variants in their immediate vicinity may promote the specific inflammatory processes underlying MMN.

Research paper thumbnail of Iatrogenic immune-mediated neuropathies: diagnostic, epidemiological and mechanistic uncertainties for causality and implications for clinical practice

Journal of Neurology, Neurosurgery, and Psychiatry, Jun 8, 2021

Acute and chronic immune-mediated neuropathies have been widely reported with medical interventio... more Acute and chronic immune-mediated neuropathies have been widely reported with medical intervention. Although causal relationship may be uncertain in many cases, a variety of drugs, several vaccination types, surgical procedures and bone marrow transplants have been reported as possible cause or trigger of a putative immune-mediated response resulting in acute and chronic neuropathies. We conducted a systematic review of the literature from 1966 to 2020 on reported cases of possible iatrogenic immune-mediated neuropathies. We determined in each case the likelihood of causality based on frequency of the association, focusing primarily on clinical presentation and disease course as well as available ancillary investigations (electrophysiology, blood and cerebrospinal fluid and neuropathology). The response to immunotherapy and issue of re-exposure were also evaluated. We also considered hypothesised mechanisms of onset of immune-mediated neuropathy in the specific iatrogenic context. We believe that a likely causal relationship exists for only few drugs, mainly antitumour necrosis factor alpha agents and immune checkpoint inhibitors, but remains largely unsubstantiated for most other suggested iatrogenic causes. Unfortunately, given the lack of an accurate diagnostic biomarker for most immune-mediated neuropathies, clinical assessment will often override ancillary investigations, resulting in lower levels of certainty that may continue to cast serious doubts on reliability of their diagnosis. Consequently, future reports of suspected cases should collect and exhaustively assess all relevant data. At the current time, besides lack of evidence for causality, the practical implications on management of suspected cases is extremely limited and therapeutic decisions appear likely no different to those made in non-iatrogenic cases.

Research paper thumbnail of Primary SARS-CoV-2 infection in patients with immune-mediated inflammatory diseases: long-term humoral immune responses and effects on disease activity

BMC Infectious Diseases, May 17, 2023

Background Patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressants (ISP... more Background Patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressants (ISPs) may have impaired long-term humoral immune responses and increased disease activity after SARS-CoV-2 infection. We aimed to investigate long-term humoral immune responses against SARS-CoV-2 and increased disease activity after a primary SARS-CoV-2 infection in unvaccinated IMID patients on ISPs. Methods IMID patients on active treatment with ISPs and controls (i.e. IMID patients not on ISP and healthy controls) with a confirmed SARS-CoV-2 infection before first vaccination were included from an ongoing prospective cohort study (T2B! study). Clinical data on infections and increased disease activity were registered using electronic surveys and health records. A serum sample was collected before first vaccination to measure SARS-CoV-2 anti-receptor-binding domain (RBD) antibodies.

Research paper thumbnail of Nerve ultrasound and magnetic resonance imaging in the diagnosis of neuropathy

Current Opinion in Neurology, Oct 1, 2018

Purpose of review This review summarizes the most relevant developments in the fields of nerve ul... more Purpose of review This review summarizes the most relevant developments in the fields of nerve ultrasound and MRI in the diagnosis of treatable inflammatory neuropathies over the last 18 months. Recent findings MRI and nerve ultrasound can accurately identify potentially treatable neuropathies and thereby help to improve diagnosis. Advanced MRI techniques also show potential to dissect pathophysiology. The apparent mismatch between nerve function and morphology is not surprising and reflects different dimensions of the disease process in neuropathies. Summary MRI and nerve ultrasound have become useful tools in the diagnosis of inflammatory neuropathies.

Research paper thumbnail of High-resolution ultrasound in diagnosis of polyneuropathies

Research paper thumbnail of Randomized double-blind placebo-controlled crossover trial with pyridostigmine in spinal muscular atrophy types 2–4

Brain communications, Dec 9, 2022

Supplementary Table 1. CONSORT Checklist CONSORT 2010 checklist of information to include when re... more Supplementary Table 1. CONSORT Checklist CONSORT 2010 checklist of information to include when reporting a randomised trial* Section/Topic Item No Checklist item Reported on page No Title and abstract 1a Identification as a randomised trial in the title 1 1b Structured summary of trial design, methods, results, and conclusions (for specific guidance see CONSORT for abstracts) 1

Research paper thumbnail of Motor unit integrity in multifocal motor neuropathy: A systematic evaluation with <scp>CMAP</scp> scans

Muscle & Nerve, Dec 16, 2021

Introduction/AimsProgressive axonal loss in multifocal motor neuropathy (MMN) is often assessed w... more Introduction/AimsProgressive axonal loss in multifocal motor neuropathy (MMN) is often assessed with nerve conduction studies (NCS), by recording maximum compound muscle action potentials (CMAPs). However, reinnervation maintains the CMAP amplitude until a significant portion of the motor unit (MU) pool is lost. Therefore, we performed more informative CMAP scans to study MU characteristics in a large cohort of patients with MMN.MethodsWe derived the maximum CMAP amplitude (CMAPmax), an MU number estimate (MUNE), and the largest MU amplitude stimulus current required to elicit 5%, 50%, and 95% of CMAPmax (S5, S50, S95) and relative ranges ([S95 − S5] × 100 / S50) from the scans. These metrics were compared with clinical, laboratory, and NCS results.ResultsForty MMN patients and 24 healthy controls were included in the study. CMAPmax and MUNE were reduced in MMN patients (both P < .001). Largest MU amplitude as a percentage of CMAPmax was increased in MMN patients (P < .001). Disease duration and treatment duration were not associated with MUNE. Relative range was larger in patients with anti‐GM1 antibodies than in those without anti‐GM1 antibodies (P = .016) and controls (P < .001). The largest MU amplitudes were larger in patients without anti‐GM1 antibodies than in patients with anti‐GM1 antibodies (P = .037) and controls (P = .044).DiscussionWe found that MU loss is common in MMN and accompanied by enlarged MUs. Presence of anti‐GM1 antibodies was associated with increased relative range of MU thresholds and reduction in largest MU amplitude. Our findings indicate that CMAP scans complement routine NCS, and may have potential for practical monitoring of treatment efficacy and disease progression.

Research paper thumbnail of Diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy in clinical practice: A survey among Dutch neurologists

Journal of The Peripheral Nervous System, Jul 9, 2020

The diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) i... more The diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is often a challenge. The clinical presentation is diverse, accurate biomarkers are lacking, and the best strategy to initiate and maintain treatment is unclear. The aim of this study was to determine how neurologists diagnose and treat CIDP. We conducted a cross-sectional survey on diagnostic and treatment practices among Dutch neurologists involved in the clinical care of CIDP patients. Forty-four neurologists completed the survey (44/71; 62%). The respondents indicated to use the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) 2010 CIDP guideline for the diagnosis in 77% and for treatment in 50%. Only 57% of respondents indicated that the presence of demyelinating electrophysiological findings was mandatory to confirm the diagnosis of CIDP. Most neurologists used intravenous immunoglobulins (IVIg) as first choice treatment, but the indications to start, optimize, or withdraw IVIg, and the use of other immune-modulatory therapies varied. University-affiliated respondents used the EFNS/PNS 2010 diagnostic criteria, nerve imaging tools, and immunosuppressive drugs more often. Despite the existence of an international guideline, there is considerable variation among neurologists in the strategies employed to diagnose and treat CIDP. More specific recommendations regarding: (a) the minimal set of electrophysiological requirements to diagnose CIDP, (b) the possible added value of nerve imaging, especially in patients not meeting the electrodiagnostic criteria, (c) the most relevant serological examinations, and (d) the clear treatment advice, in the new EFNS/PNS guideline, would likely support its implementation in clinical practice.

Research paper thumbnail of Value and pitfalls of imaging and electrodiagnosis in neurogenic thoracic outlet syndrome: Lessons learned from present and past

Muscle & Nerve, Oct 21, 2021

See article on pages 34–42 in this issue.

Research paper thumbnail of Thoracic outlet syndrome (TROTS) registry: A study protocol for the primary upper extremity deep venous thrombosis section

PLOS ONE, Jan 6, 2023

Introduction There is a lack of comprehensive and uniform data on primary upper extremity deep ve... more Introduction There is a lack of comprehensive and uniform data on primary upper extremity deep venous thrombosis (pUEDVT). pUEDVT includes venous thoracic outlet syndrome related upper extremity deep venous thrombosis (UEDVT) and idiopathic UEDVT. Research on these conditions has been hampered by their rarity, lack of uniform diagnostic criteria, and heterogeneity in therapeutic strategies. To improve current research data collection using input of all various pUEDVT treating medical specialists, we initiated the ThoRacic OuTlet Syndrome (TROTS) registry. The aim of the TROTS registry is to a) collect extensive data on all pUEDVT patients through a predefined protocol, b) give insight in the long term outcome using patient reported outcome measures, c) create guidance in the diagnostic and clinical management of these conditions, and thereby d) help provide content for future research. Methods and analysis The TROTS registry was designed as an international prospective longitudinal observational registry for data collection on pUEDVT patients. All pUEDVT patients, regardless of treatment received, can be included in the registry after informed consent is obtained. All relevant data regarding the initial presentation, diagnostics, treatment, and follow-up will be collected prospectively in an electronic case report form. In addition, a survey containing general questions, a Health-related Quality of Life questionnaire (EQ-5D-5L), and Functional Disability questionnaire (Quick-DASH) will be sent periodically (at the time of inclusion, one and two years after inclusion, and every five years after inclusion) to the participant. The registry protocol was approved by the Medical Ethical Review Board and registered in the Netherlands Trial Register under Trial-ID NL9680. The data generated by

Research paper thumbnail of MRI shows thickening and altered diffusion in the median and ulnar nerves in multifocal motor neuropathy

European Radiology, Sep 21, 2016

Objectives To study disease mechanisms in multifocal motor neuropathy (MMN) with magnetic resonan... more Objectives To study disease mechanisms in multifocal motor neuropathy (MMN) with magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) of the median and ulnar nerves. Methods We enrolled ten MMN patients, ten patients with amyotrophic lateral sclerosis (ALS) and ten healthy controls (HCs). Patients underwent MRI (in a prone position) and nerve conduction studies. DTI and fat-suppressed T2-weighted scans of the forearms were performed on a 3.0T MRI scanner. Fibre tractography of the median and ulnar nerves was performed to extract diffusion parameters: fractional anisotropy (FA), mean (MD), axial (AD) and radial (RD) diffusivity. Cross-sectional areas (CSA) were measured on T2-weighted scans. Results Forty-five out of 60 arms were included in the analysis. AD was significantly lower in MMN patients (2.20 ± 0.12 × 10-3 mm 2 /s) compared to ALS patients (2.31 ± 0.17 × 10-3 mm 2 /s; p < 0.05) and HCs (2.31 ± 0.17 × 10-3 mm 2 /s; p < 0.05). Segmental analysis showed significant restriction of AD, RD and MD (p < 0.005) in the proximal third of the nerves. CSA was significantly larger in MMN patients compared to ALS patients and HCs (p < 0.01). Conclusions Thickening of nerves is compatible with changes in the myelin sheath structure, whereas lowered AD values suggest axonal dysfunction. These findings suggest that myelin and axons are diffusely involved in MMN pathogenesis. Key Points • Diffusion magnetic resonance imaging provides quantitative information about multifocal motor neuropathy (MMN). • Diffusion tensor imaging allows non-invasive evaluation of the forearm nerves in MMN. • Nerve thickening and lowered diffusion parameters suggests myelin and axonal changes. • This study can help to provide insight into pathological mechanisms of MMN.

Research paper thumbnail of Sonomorphology of median nerve in relation to function: Important lessons from carpal tunnel but still complex

Clinical Neurophysiology Practice, 2023

Research paper thumbnail of The relation between nerve morphology detected by sonography and electrodiagnostic findings

Clinical Neurophysiology, Jul 1, 2014

Fig. 1. The figure shows a model of different types of mononeuropathies in relation to the presen... more Fig. 1. The figure shows a model of different types of mononeuropathies in relation to the presence and severity of loss of motor or sensory loss (clinically or by electrodiagnostic testing), time and severity of nerve enlargement detected by HRUS.

Research paper thumbnail of Ultrasound scanning in the diagnosis of peripheral neuropathies

Practical Neurology, Feb 4, 2021

Nerve ultrasound scanning has become a valuable diagnostic tool in the routine workup of peripher... more Nerve ultrasound scanning has become a valuable diagnostic tool in the routine workup of peripheral nerve disorders, effectively complementing conventional electrodiagnostic studies. The most relevant sonographic features are nerve size and structural integrity. Several peripheral neuropathies show characteristic and distinct patterns of nerve enlargement, allowing their early and accurate identification, and reducing test-burden and diagnostic delay for patients. In mononeuropathies such as carpal tunnel syndrome and ulnar neuropathy at the elbow, nerve enlargement develops only at specific sites of entrapment, while in polyneuropathy the nerve enlargement may be multifocal, regional or even diffuse. Nerve ultrasound scanning can reliably identify chronic inflammatory neuropathies, even when extensive electrodiagnostic studies fail, and it should therefore be embedded in routine diagnostic workup of peripheral neuropathies. In this paper we describe a potential diagnostic strategy to achieve this.

Research paper thumbnail of The use and misuse of sonographic reference values in neuromuscular disease

Muscle & Nerve, Apr 27, 2023

Research paper thumbnail of Correlates of Fatigability in Patients With Spinal Muscular Atrophy

Neurology, Nov 20, 2020

Disclosure Statement Bart Bartels obtained research grants from Prinses Beatrix Spierfonds and St... more Disclosure Statement Bart Bartels obtained research grants from Prinses Beatrix Spierfonds and Stichting Spieren voor Spieren, both non-profit foundations. His employer receives fees for SMA-related consultancy activities Janke F. de Groot reports no disclosure Laura E. Habets reports no disclosure Fay-Lynn Asselman reports no disclosure Rense I. Wadman obtained research grant from Stichting Spieren voor Spieren, a non-profit foundation. Edward E. S. Nieuwenhuis reports no disclosure Ruben P.A. van Eijk reports no disclosure H. Stephan Goedee obtained research grants from Prinses Beatrix Spierfonds, a non-profit foundation and received travel grants and speaker fees from Shire/Takeda. W. Ludo van der Pol obtained research grants from Prinses Beatrix Spierfonds and Stichting Spieren voor Spieren, both non-profit foundations. His employer receives fees for SMA-related consultancy activities

Research paper thumbnail of Nerve ultrasound

Neurology, Dec 28, 2018

ObjectiveTo determine interobserver variability of nerve ultrasound in peripheral neuropathy in a... more ObjectiveTo determine interobserver variability of nerve ultrasound in peripheral neuropathy in a prospective, systematic, multicenter study.MethodsWe enrolled 20 patients with an acquired chronic demyelinating or axonal polyneuropathy and 10 healthy controls in 3 different centers. All participants underwent an extensive nerve ultrasound protocol, including cross-sectional area measurements of median, ulnar, fibular, tibial, and sural nerves, and brachial plexus. Real-time image acquisition was performed blind by a local and a visiting investigator (reference). Five patients were investigated using different types of sonographic devices. Intraclass correlation coefficients were calculated, and a random-effects model was fitted to identify factors with significant effect on interobserver variability.ResultsSystematic differences between measurements made by different investigators were small (mean difference 0.11 mm2 [95% confidence interval 0.00–0.23 mm2]). Intraclass correlation coefficients were generally higher in arm nerves (0.48–0.96) than leg nerves (0.46–0.61). The hospital site and sonographic device did not contribute significantly to interobserver variability in the random-effects model.ConclusionsInterobserver variability of nerve ultrasound in peripheral neuropathy is generally limited, especially in arm nerves. Different devices and a multicenter setting have no effect on interobserver variability. Therefore, nerve ultrasound is a reproducible tool for diagnostics in routine clinical practice and (multicenter) research.

Research paper thumbnail of Diagnostic accuracy of MRI and ultrasound in chronic immune-mediated neuropathies

Neurology, Dec 11, 2019

Objective To assess and compare the diagnostic performance of qualitative and (semi-)quantitative... more Objective To assess and compare the diagnostic performance of qualitative and (semi-)quantitative MRI and ultrasound for distinguishing chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN) from segmental spinal muscular atrophy (sSMA). Methods Patients with CIDP (n = 13), MMN (n = 10), or sSMA (n = 12) and healthy volunteers (n = 30) were included. MRI of the brachial plexus, using short tau inversion recovery (STIR), nervespecific T2-weighted (magnetic resonance neurography [MRN]), and diffusion tensor imaging (DTI) sequences, was evaluated. Furthermore, with ultrasound, cross-sectional areas of the nerves were evaluated. Three radiologists blinded for diagnosis qualitatively scored hypertrophy and increased signal intensity (STIR and MRN), and intraobserver and interobserver agreement was assessed. For the (semi-)quantitative modalities, group differences and receiver operator characteristics were calculated. Results Hypertrophy and increased signal intensity were found in all groups including healthy controls. Intraobserver and interobserver agreements varied considerably (intraclass correlation coefficients 0.00-0.811 and 0.101-0.491, respectively). DTI showed significant differences (p < 0.05) among CIDP, MMN, sSMA, and controls for fractional anisotropy, axial diffusivity, and radial diffusivity in the brachial plexus. Ultrasound showed significant differences in crosssectional area (p < 0.05) among CIDP, MMN, and sSMA in upper arm and brachial plexus. For distinguishing immune-mediated neuropathies (CIDP and MMN) from sSMA, ultrasound yielded the highest area under the curve (0.870). Conclusion Qualitative assessment of hypertrophy and signal hyperintensity on STIR or MRN is of limited value. DTI measures may discriminate among CIDP, MMN, and sSMA. Currently, ultrasound may be the most appropriate diagnostic imaging aid in the clinical setting.

Research paper thumbnail of To treat or not to treat mild Guillain-Barré syndrome: limited evidence for but still none against

Journal of Neurology, Neurosurgery, and Psychiatry, Jun 8, 2021

There are several caveats to the use of terminology ‘mild GuillainBarré syndrome (GBS)’ in clinic... more There are several caveats to the use of terminology ‘mild GuillainBarré syndrome (GBS)’ in clinical settings, as this is at present mainly based on motor function of legs and does not include weakness of arms nor other disabling dysfunctions such as ataxia. Moreover, some patients may progress beyond mild, but accurate biomarkers to timely identify this subset are lacking. Corroborating with the shift to less conservative ischaemic stroke treatment, where progression is no longer awaited and disabling symptoms such as exclusively aphasia may be considered appropriate thresholds for treatment with intravenous alteplase, the ‘inflammatory penumbra’ in GBS could be considered to benefit from timely and appropriate treatment (figure 1). In practice, treatment of GBS will often not be delayed when progression is suspected clinically, or dysfunction is still considered sufficiently disabling. Nevertheless, treatment of mild GBS remains a difficult decision in clinical practice. Only plasma exchange (PE) has been studied in this setting with a single randomised controlled trial. This trial performed over two decades ago, showed the benefit of two PE sessions in subjects with GBS still able to walk, in shortening time of onset of motor recovery. No trials of intravenous immunoglobulins (Ig) have been performed in mild GBS, but equivalence of PE and intravenous Ig is generally assumed, supported by data from five comparative studies. Hence, intravenous Ig is often used in this setting, mainly for practical reasons (ie, access route and availability of PE service) (figure 1). Verboon reports the findings of an analysis on a multicentre observational study from a sample of patients with mild GBS, derived from the prospective observational international GBS outcome study, and defined as being able to walk independently, comparing treated with intravenous Ig with receiving supportive care only. The effect of intravenous Ig was evaluated at 4 and 26 weeks by the GBS disability scale. However, floor effect hampered responsiveness as the maximal range of change on this scale was only two points with mild GBS already at lower end. Corrections were performed for a number of known prognostic factors, as well as for early improvement. After one course of intravenous Ig, no differences on GBS disability score were detected at 4 (primary endpoint) and 26 weeks (first secondary endpoint). However, the lack of response on GBS disability scale does not necessarily imply no effect, but may also indicate inaccuracy of this outcome measure to detect smaller changes that could still be clinically relevant. Of note, the time needed to reach full muscle strength was shortened in the intravenous Igtreated group from 56 to 28 days (p=0.03). Pain was otherwise less common in the intravenous Igtreated group at 26 weeks (22% vs 40%, p=0.04). In summary, both intravenous Ig and PE may shorten

Research paper thumbnail of MRI of the intraspinal nerve roots in patients with chronic inflammatory neuropathies: abnormalities correlate with clinical phenotypes

Journal of Neurology, Jan 6, 2022

Chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN) ar... more Chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN) are caused by inflammatory changes of peripheral nerves. It is unknown if the intra-spinal roots are also affected. This MRI study systematically visualized intra-spinal nerve roots, i.e., the ventral and dorsal roots, in patients with CIDP, MMN and motor neuron disease (MND). We performed a cross-sectional study in 40 patients with CIDP, 27 with MMN and 34 with MND. All patients underwent an MRI scan of the cervical intra-spinal roots. We systematically measured intra-spinal nerve root sizes bilaterally in the transversal plane at C5, C6 and C7 level. We calculated mean nerve root sizes and compared them between study groups and between different clinical phenotypes using a univariate general linear model. Patients with MMN and CIDP with a motor phenotype had thicker ventral roots compared to patients with CIDP with a sensorimotor phenotype (p = 0.012), while patients with CIDP with a sensory phenotype had thicker dorsal roots compared to patients with a sensorimotor phenotype (p = 0.001) and with MND (p = 0.004). We here show changes in the morphology of intra-spinal nerve roots in patients with chronic inflammatory neuropathies, compatible with their clinical phenotype.

Research paper thumbnail of High-resolution mapping identifies HLA class II associations with multifocal motor neuropathy

Neurobiology of Aging, May 1, 2021

OBJECTIVE To gain further insight in the immunopathology underlying multifocal motor neuropathy (... more OBJECTIVE To gain further insight in the immunopathology underlying multifocal motor neuropathy (MMN) by exploring the association between MMN and the human leukocyte antigen (HLA) class II DRB1, DQB1, and DQA loci in depth and by correlating associated haplotypes to detailed clinical and anti-ganglioside antibody data. METHODS We performed high-resolution HLA-class II typing for the DRB1, DQB1, and DQA1 loci in 126 well-characterized MMN patients and assessed disease associations with haplotypes. We used a cohort of 1305 random individuals as a reference for haplotype distribution in the Dutch population. RESULTS The DRB1*15:01-DQB1*06:02 haplotype (OR 1.6 [95% CI 1.1-2.2], p < 0.05) and the DRB1*12:01-DQB1*03:01 haplotype (OR 2.7 [95% CI 1.2-5.5], p < 0.05) were more frequent in patients with MMN than in controls. These haplotypes were not associated with disease course, response to treatment or anti-ganglioside antibodies. CONCLUSIONS MMN is associated with the DRB1*15:01-DQB1*06:02 and DRB1*12:01-DQB1*03:01 haplotypes. These HLA molecules or gene variants in their immediate vicinity may promote the specific inflammatory processes underlying MMN.

Research paper thumbnail of Iatrogenic immune-mediated neuropathies: diagnostic, epidemiological and mechanistic uncertainties for causality and implications for clinical practice

Journal of Neurology, Neurosurgery, and Psychiatry, Jun 8, 2021

Acute and chronic immune-mediated neuropathies have been widely reported with medical interventio... more Acute and chronic immune-mediated neuropathies have been widely reported with medical intervention. Although causal relationship may be uncertain in many cases, a variety of drugs, several vaccination types, surgical procedures and bone marrow transplants have been reported as possible cause or trigger of a putative immune-mediated response resulting in acute and chronic neuropathies. We conducted a systematic review of the literature from 1966 to 2020 on reported cases of possible iatrogenic immune-mediated neuropathies. We determined in each case the likelihood of causality based on frequency of the association, focusing primarily on clinical presentation and disease course as well as available ancillary investigations (electrophysiology, blood and cerebrospinal fluid and neuropathology). The response to immunotherapy and issue of re-exposure were also evaluated. We also considered hypothesised mechanisms of onset of immune-mediated neuropathy in the specific iatrogenic context. We believe that a likely causal relationship exists for only few drugs, mainly antitumour necrosis factor alpha agents and immune checkpoint inhibitors, but remains largely unsubstantiated for most other suggested iatrogenic causes. Unfortunately, given the lack of an accurate diagnostic biomarker for most immune-mediated neuropathies, clinical assessment will often override ancillary investigations, resulting in lower levels of certainty that may continue to cast serious doubts on reliability of their diagnosis. Consequently, future reports of suspected cases should collect and exhaustively assess all relevant data. At the current time, besides lack of evidence for causality, the practical implications on management of suspected cases is extremely limited and therapeutic decisions appear likely no different to those made in non-iatrogenic cases.