ERare diseases’ management guidelines are produced with the primary aim of improving practice and standards of care for patients and may represent a useful framework for clinical practice. The EFNS/PNS (European Federation of Neurological Societies/Peripheral Nerve Society) guidelines for CIDP (chronic inflammatory demyelinating polyneuropathy) and MMN (multifocal motor neuropathy) were last published in 2010 (1, 2). Enthusiasm of the audience for whom they are produced, arguably primarily non‐sub‐specialists, is however largely unexplored. Compliance to these guidelines by neuromuscular and/or peripheral nerve specialists has not been investigated

A. Fowle

A. Uncini

E. Nobile-Orazio

J. Leger

P. van den Bergh

P. van Doorn

Y.A. Rajabally

English

Crossref

Compliance with international guidelines for chronic inflammatory neuropathies

AIR Universita degli studi di Milano

Compliance with international guidelines 
for chronic inflammatory neuropathies 
 
 
Yusuf A. Rajabally,1        Peter van den Bergh,2    for the European Study Group on 
Guidelines for Neuropathy* 
 
1. School of Life & Health Sciences, Aston Brain Centre, Aston University, 
Birmingham, U.K. 
2. Centre Neuromusculaire, Cliniques Universitaires St. Luc, Université Catholique de 
Louvain, Brussels, Belgium. 
 
*Adrian Fowle,3 Jean-Marc Leger,4   Eduardo Nobile-Orazio,5 Antonino Uncini6 and 
Pieter van Doorn.7 
3. Department of Clinical Neurophysiology, St. Peter’s Hospital, Chertsey, U.K. 
4. Neuromuscular and Neuroimmunology Service, University of Milan, Milan, Italy. 
5. National Referral Center for Rare Neuromuscular Diseases, Hospital Pitié-Salpêtrière, 
University Pierre et Marie Curie (Paris VI), Paris, France. 
6. Department of Neuroscience, Imaging and Clinical Sciences, University "G. 
d'Annunzio", Chieti, Italy. 
7. Erasmus MC University Medical Centre, Rotterdam, Netherlands. 
 
EDITORIAL 
Word Count: 1041 
References: 8 
Conflicts of Interest: None for this work 
Abbreviations:  CIDP: chronic inflammatory demyelinating polyneuropathy; EFNS/PNS: 
European Federation of Neurological Societies/Peripheral Nerve Society; MMN: multifocal 
motor neuropathy 
Correspondence to: 
Yusuf A. Rajabally, School of Life & Health Sciences, Aston Brain Centre, Aston 
University, Aston Triangle, Birmingham B4 7ET, U.K.  e-mail: y.rajabally@aston.ac.uk 
 
Rare diseases’ management guidelines are produced with the primary aim of improving 
practice and standards of care for patients and may represent a useful framework for clinical 
practice. The EFNS/PNS (European Federation of Neurological Societies/Peripheral Nerve 
Society) guidelines for CIDP (chronic inflammatory demyelinating polyneuropathy) and 
MMN (multifocal motor neuropathy) were last published in 2010 (1, 2).  Enthusiasm of the 
audience for whom they are produced, arguably primarily non-sub-specialists, is however 
largely unexplored. Compliance to these guidelines by neuromuscular and/or peripheral nerve 
specialists has not been investigated. 
In this issue of the journal, Rosier et al. describe the findings of their study specifically in 
relation to intravenous immunoglobulin (IVIg) treatment (3). They aimed, through a survey, 
to evaluate French daily neurological practice in relation to the above-mentioned published 
guidelines. They performed a retrospective observational study based on a pilot questionnaire 
validated by expert neurologists in the field. Four hundred and eleven neurologists were 
invited by e-mail to fill a general questionnaire and 4 patient case reports concerning recently 
seen or soon to be seen subjects. Of the 70 responders, 49 met pre-defined criteria for 
inclusion in the analysis. A minority (26.6%) worked in neuromuscular reference centres 
(NRCs), coming from most (10 of the 13 existing) of the French NRCs, thereby offering an 
adequate global view of subspecialist practice. The authors mainly ascertained that initial 
treatment procedures for both CIDP and MMN conformed to existing guidelines. However, 
in greater detail, this essentially concerns the dose of 2g/kg used over 5 days, the 4-weekly 
administration frequency with dose maintenance for the first 3 courses. In contrast, in relation 
to longer term therapy and guideline recommendations, some major and interesting 
discrepancies were observed, notably with non-NRC neurologist decreasing significantly 
more frequently the dose of IVIg than NRC neurologists (83% vs. 51%; p<0.05) and using 
immunosuppressants significantly less frequently (39% vs. 92%; p<0.05). 
Immunosuppressants were used for nearly 40% of cases by neurologists and although the 
details are not provided, it would be likely this practice was more common in NRCs. Dose 
reductions are recommended in the guidelines and implementation of this appears from the 
reported findings of Rosier et al., less widespread amongst subspecialists. One may argue that 
NRCs see more severely affected subjects, although how this may justify sustained high dose 
therapy, presumably in circumstances of stability or progressive and possibly treatment-
unrelated improvement, for over a quarter of subspecialists for the first 12 courses, is 
somewhat mystifying. This is compounded by the two-fold and four-fold higher follow-up 
frequencies of CIDP and MMN patients respectively, in NRCs compared to the general 
neurology setting, which one would have expected making dose reduction decisions easier. 
On the other hand, the use of immunosuppressants, for which there is no current evidence 
base, is not recommended by the existing guidelines neither for CIDP nor for MMN. Despite 
this lack of justification, subspecialists appear to widely diverge from the recommendations 
in their practice, as opposed to generalists. Also, of note, and in relation to published data on 
the usually fixed frequency requirements particularly in CIDP (4, 5), all neurologists in 
contrast, more frequently altered treatment interval rather than dose (97% vs. 65% for CIDP 
and 98% vs. 51% for MMN).   
These findings in themselves clearly therefore suggest poor longer-term compliance to the 
guidelines, which importantly, but also perplexingly, appears to predominate in NRCs. That 
nearly a third of patients with CIDP and nearly half of those with MMN were referred by 
general neurologists to NRCs suggests that cases managed by subspecialists do not majorly 
differ in presentation or progression to those whose treatment remained in the hands of 
general neurologists. It is clear however that subsequent patient management differs 
significantly within as compared to outside NRCs, this in itself, irrespective of hypothetical 
underlying reasons, being inconsistent with the aim and objectives of guideline generation 
and dissemination. 
Our group conducted an international web-based audit on compliance to EFNS/PNS 
Guidelines on CIDP and MMN between 2012 and 2015 in 9 countries in total: Italy, 
Belgium, Serbia, Moldova, France, Hungary, Portugal, the United Kingdom and the state of 
Kerala in India. The main finding of our audit was the low response rate (globally 4.2% of all 
contacted potential participants). Nearly 60% of non-neuromuscular neurologists stated that 
they used EFNS/PNS Guidelines to establish their therapeutic decision-making for CIDP and 
MMN. Nearly a sixth had however no knowledge of the Guidelines, the electrophysiological 
features being as expected, less commonly known than the clinical aspects. A large majority 
of neuromuscular neurologists preferred using EFNS/PNS criteria in clinical practice than 
any other criteria. Intravenous immunoglobulin dose reduction trials were, in contrast to 
Rosier et al.’s findings, reported as common practice for the majority of neuromuscular 
neurologists, for long-term patients. Although in lower proportions as compared to the French 
study, over 50% of neuromuscular neurologists declared feeling immunosuppression may be 
justified in CIDP, irrespective of the response to steroids, immunoglobulins or plasma 
exchange.  
Our analysis, through the poor responder rate from a large, similarly sampled, e-mailed 
invited, international neurological cohort, demonstrates a low level of interest in guidelines 
for rare diseases such as CIDP and MMN, particularly amongst general neurologists. 
Furthermore, a selection bias is likely to have occurred, as illustrated by the contrasting high 
level of guideline awareness in the surveyed sample. A similar selection bias is also likely in 
Rosier et al.’s study. Our results indicate that the surveyed sample was aware of the 
guidelines, but similarly to the French cohort, behaved variably in relation to the 
recommendations within them.  
Current EFNS/PNS guidelines represent very useful research tools as we have shown in a 
previous analysis (6). Awareness and compliance to these guidelines appear however, both 
from the data from Rosier et al. and from our international analysis, much more doubtful. In 
the French study, the poor long-term compliance amongst NRC neurologists enhances the 
concerns, indicating the need for greater coherence in the subspecialist arena, so as to 
improve newer versions and updates for all practitioners at large. New guidelines will be 
necessarily and rightly focused on the evidence base (7, 8). However, consideration of factors 
impacting on dissemination and uptake will equally require careful consideration. It may be 
hoped this will ultimately allow the improvement and harmonisation of standards of care of 
all affected patients.  
 
 
  
 
 
 
 
 
 
 
 
 
References 
 
1. European Federation of Neurological Societies/Peripheral Nerve Society guideline on 
management of multifocal motor neuropathy. Report of a joint task force of the European 
Federation of Neurological Societies and the Peripheral Nerve Society--first revision. Journal of the 
peripheral nervous system : JPNS. 2010;15(4):295-301. 
2. Van den Bergh PY, Hadden RD, Bouche P, Cornblath DR, Hahn A, Illa I, et al. European 
Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic 
inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European 
Federation of Neurological Societies and the Peripheral Nerve Society - first revision. European 
journal of neurology. 2010;17(3):356-63. 
3. Rosier C, Graveline N, Lacour A, Antoine JC, Camdessanche JP. IGIV for chronic inflammatory 
demyelinating polyneuropathies and multifocal motor neuropathies treatment in France: are daily 
practices in accordance with guidelines? European journal of neurology. 2018. 
4. Lunn MP, Ellis L, Hadden RD, Rajabally YA, Winer JB, Reilly MM. A proposed dosing algorithm 
for the individualized dosing of human immunoglobulin in chronic inflammatory neuropathies. 
Journal of the peripheral nervous system : JPNS. 2016;21(1):33-7. 
5. Rajabally YA, Seow H, Wilson P. Dose of intravenous immunoglobulins in chronic 
inflammatory demyelinating polyneuropathy. Journal of the peripheral nervous system : JPNS. 
2006;11(4):325-9. 
6. Rajabally YA, Fowle AJ, Van den Bergh PY. Which criteria for research in chronic 
inflammatory demyelinating polyradiculoneuropathy? an analysis of current practice. Muscle & 
nerve. 2015;51(6):932-3. 
7. Guyatt GH, Oxman AD, Schunemann HJ, Tugwell P, Knottnerus A. GRADE guidelines: a new 
series of articles in the Journal of Clinical Epidemiology. Journal of clinical epidemiology. 
2011;64(4):380-2. 
8. Malmivaara A. Methodological considerations of the GRADE method. Annals of medicine. 
2015;47(1):1-5. 
 


Rare diseases’ management guidelines are produced with the primary aim of improving practice and standards of care for patients and may represent a useful framework for clinical practice. The EFNS/PNS (European Federation of Neurological Societies/Peripheral Nerve Society) guidelines for CIDP (chronic inflammatory demyelinating polyneuropathy) and MMN (multifocal motor neuropathy) were last published in 2010 (1, 2). Enthusiasm of the 
audience for whom they are produced, arguably primarily non-sub-specialists, is however largely unexplored. Compliance to these guidelines by neuromuscular and/or peripheral nerve specialists has not been investigated. [...

Rajabally, Yusuf A

Van den Bergh, Peter

European Study Group on Guidelines for Neuropathy

DIAL UCLouvain

Compliance with international guidelines for chronic inflammatory neuropathies.

The European Study Group on Guidelines for Neuropathy

Aston Publications Explorer

Accepted ArticleThis article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/ene.13873 This article is protected by copyright. All rights reserved. DR. YUSUF A. RAJABALLY (Orcid ID : 0000-0002-7170-8343)  Article type      : Editorials  Compliance with international guidelines for chronic inflammatory neuropathies  Yusuf A. Rajabally,1        Peter van den Bergh,2    for the European Study Group on Guidelines for Neuropathy*  1. School of Life & Health Sciences, Aston Brain Centre, Aston University, Birmingham, U.K. 2. Centre Neuromusculaire, Cliniques Universitaires St. Luc, Université Catholique de Louvain, Brussels, Belgium.  *Adrian Fowle,3 Jean-Marc Leger,4   Eduardo Nobile-Orazio,5 Antonino Uncini6 and Pieter van Doorn.7 3. Department of Clinical Neurophysiology, St. Peter’s Hospital, Chertsey, U.K. 4. National Referral Center for Rare Neuromuscular Diseases, Hospital Pitié-Salpêtrière, University Pierre et Marie Curie (Paris VI), Paris, France. Accepted ArticleThis article is protected by copyright. All rights reserved. 5. Neuromuscular and Neuroimmunology Service, University of Milan, Milan, Italy. 6. Department of Neuroscience, Imaging and Clinical Sciences, University "G. d'Annunzio", Chieti, Italy. 7. Erasmus MC University Medical Centre, Rotterdam, Netherlands.  Conflicts of Interest: None for this work  Abbreviations:  CIDP: chronic inflammatory demyelinating polyneuropathy; EFNS/PNS: European Federation of Neurological Societies/Peripheral Nerve Society; MMN: multifocal motor neuropathy  Correspondence to: Yusuf A. Rajabally, School of Life & Health Sciences, Aston Brain Centre, Aston University, Aston Triangle, Birmingham B4 7ET, U.K.  e-mail: y.rajabally@aston.ac.uk  ERare diseases’ management guidelines are produced with the primary aim of improving practice and standards of care for patients and may represent a useful framework for clinical practice. The EFNS/PNS (European Federation of Neurological Societies/Peripheral Nerve Society) guidelines for CIDP (chronic inflammatory demyelinating polyneuropathy) and MMN (multifocal motor neuropathy) were last published in 2010 (1, 2).  Enthusiasm of the audience for whom they are produced, arguably primarily non-sub-specialists, is however Accepted ArticleThis article is protected by copyright. All rights reserved. largely unexplored. Compliance to these guidelines by neuromuscular and/or peripheral nerve specialists has not been investigated. In this issue of the journal, Rosier et al. describe the findings of their study specifically in relation to intravenous immunoglobulin (IVIg) treatment for these disorders (3). They aimed, through a survey, to evaluate French daily neurological practice in relation to the above-mentioned published guidelines. They performed a retrospective observational study based on a pilot questionnaire validated by expert neurologists in the field. Four hundred and eleven neurologists were invited by e-mail to fill a general questionnaire and 4 patient case reports concerning recently seen or soon to be seen subjects. Of the 70 responders, 49 met pre-defined criteria for inclusion in the analysis. A minority (26.6%) worked in neuromuscular reference centres (NRCs), coming from most (10 of the 13 existing) of the French NRCs, thereby offering an adequate global view of subspecialist practice. The authors mainly ascertained that initial treatment procedures for both CIDP and MMN conformed to existing guidelines. However, in greater detail, this essentially concerns the dose of 2g/kg used over 5 days, the 4-weekly administration frequency with dose maintenance for the first 3 courses. In contrast, in relation to longer term therapy and guideline recommendations, some major and interesting discrepancies were observed, notably with non-NRC neurologist decreasing significantly more frequently the dose of IVIg than NRC neurologists (83% vs. 51%; p<0.05) and using immunosuppressants significantly less frequently (39% vs. 92%; p<0.05). Immunosuppressants were used for nearly 40% of cases by neurologists and although the details are not provided, it would be likely this practice was more common in NRCs. Dose reductions are recommended in the guidelines and implementation of this, appears from the reported findings of Rosier et al., less widespread amongst subspecialists. One may argue that NRCs see more severely affected subjects, although how this may justify sustained high dose therapy, presumably in circumstances of stability or progressive and possibly treatment-Accepted ArticleThis article is protected by copyright. All rights reserved. unrelated improvement, for over a quarter of subspecialists for the first 12 treatment courses, is somewhat mystifying. This is compounded by the two-fold and four-fold higher follow-up frequencies of CIDP and MMN patients respectively, in NRCs compared to the general neurology setting, which one would have expected making dose reduction decisions easier. On the other hand, the use of immunosuppressants, for which there is no current evidence base, is not recommended by the existing guidelines neither for CIDP nor for MMN. Despite this lack of justification, subspecialists appear to widely diverge from the recommendations in their practice, as opposed to generalists. Also, of note, and in relation to published data on the usually fixed frequency requirements particularly in CIDP (4, 5), all neurologists in contrast, more frequently altered treatment interval rather than dose (97% vs. 65% for CIDP and 98% vs. 51% for MMN).   These findings in themselves clearly therefore suggest poor longer-term compliance to the guidelines, which importantly, but also perplexingly, appears to predominate in NRCs. That nearly a third of patients with CIDP and nearly half of those with MMN were referred by general neurologists to NRCs suggests that cases managed by subspecialists do not majorly differ in presentation or progression to those whose treatment remained in the hands of general neurologists. It is clear however that subsequent patient management differs significantly within as compared to outside NRCs, this in itself, irrespective of hypothetical underlying reasons, being inconsistent with the aim and objectives of guideline generation and dissemination. Our group conducted an international web-based audit on compliance to EFNS/PNS Guidelines on CIDP and MMN between 2012 and 2015 in 9 countries in total: Italy, Belgium, Serbia, Moldova, France, Hungary, Portugal, the United Kingdom and the state of Kerala in India. The main finding of our audit was the low response rate (globally 4.2% of all contacted potential participants). Nearly 60% of non-neuromuscular neurologists stated that Accepted ArticleThis article is protected by copyright. All rights reserved. they used EFNS/PNS Guidelines to establish their therapeutic decision-making for CIDP and MMN. Nearly a sixth had however no knowledge of the Guidelines, the electrophysiological features being as expected, less commonly known than the clinical aspects. A large majority of neuromuscular neurologists preferred using EFNS/PNS criteria in clinical practice than any other criteria. Intravenous immunoglobulin dose reduction trials were, in contrast to Rosier et al.’s findings, reported as common practice for the majority of neuromuscular neurologists, for long-term patients. Although in lower proportions as compared to the French study, over 50% of neuromuscular neurologists declared feeling immunosuppression may be justified in CIDP, irrespective of the response to steroids, immunoglobulins or plasma exchange.  Our analysis, through the poor responder rate from a large, similarly sampled, e-mailed invited, international neurological cohort, demonstrates a low level of interest in guidelines for rare diseases such as CIDP and MMN, particularly amongst general neurologists. Furthermore, a selection bias is likely to have occurred, as illustrated by the contrasting high level of guideline awareness in the surveyed sample. A similar selection bias is also likely in Rosier et al.’s study. Our results indicate that the surveyed sample was aware of the guidelines, but similarly to the French cohort, behaved variably in relation to the recommendations within them.  Current EFNS/PNS guidelines represent very useful research tools as we have shown in a previous analysis (6). Awareness and compliance to these guidelines appear however, both from the data from Rosier et al. and from our international analysis, much more doubtful. In the French study, the poor long-term compliance amongst NRC neurologists enhances the concerns, indicating the need for greater coherence in the subspecialist arena, so as to improve newer versions and updates for all practitioners at large. New guidelines will be necessarily and rightly focused on the evidence base (7, 8). However, consideration of factors Accepted ArticleThis article is protected by copyright. All rights reserved. impacting on dissemination and uptake will equally require careful consideration. It may be hoped this will ultimately allow the improvement and harmonisation of standards of care of all affected patients.   References  1. European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of multifocal motor neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society--first revision. Journal of the peripheral nervous system : JPNS. 2010;15(4):295-301. 2. Van den Bergh PY, Hadden RD, Bouche P, Cornblath DR, Hahn A, Illa I, et al. European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society - first revision. European journal of neurology. 2010;17(3):356-63. 3. Rosier C, Graveline N, Lacour A, Antoine JC, Camdessanche JP. IGIV for chronic inflammatory demyelinating polyneuropathies and multifocal motor neuropathies treatment in France: are daily practices in accordance with guidelines? European journal of neurology. 2018. 4. Lunn MP, Ellis L, Hadden RD, Rajabally YA, Winer JB, Reilly MM. A proposed dosing algorithm for the individualized dosing of human immunoglobulin in chronic inflammatory neuropathies. Journal of the peripheral nervous system : JPNS. 2016;21(1):33-7. Accepted ArticleThis article is protected by copyright. All rights reserved. 5. Rajabally YA, Seow H, Wilson P. Dose of intravenous immunoglobulins in chronic inflammatory demyelinating polyneuropathy. Journal of the peripheral nervous system : JPNS. 2006;11(4):325-9. 6. Rajabally YA, Fowle AJ, Van den Bergh PY. Which criteria for research in chronic inflammatory demyelinating polyradiculoneuropathy? an analysis of current practice. Muscle & nerve. 2015;51(6):932-3. 7. Guyatt GH, Oxman AD, Schunemann HJ, Tugwell P, Knottnerus A. GRADE guidelines: a new series of articles in the Journal of Clinical Epidemiology. Journal of clinical epidemiology. 2011;64(4):380-2. 8. Malmivaara A. Methodological considerations of the GRADE method. Annals of medicine. 2015;47(1):1-5.   

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Compliance with international guidelines for chronic inflammatory neuropathies

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