Highlights
- •PINS appears as myelitis (44%), encephalomyelitis (44%) or encephalitis (12%).
- •PINS involve the peripheral nervous system in 41% of cases.
- •The new set of MS risk alleles does not increase the risk of developing PINS.
- •MS and PINS have a different etiology, and they need to be treated differently.
ABSTRACT
Background
The genetic component of multiple sclerosis (MS) is now set to 200 autosomal common
variants. However, it is unclear how genetic knowledge be clinically used in the differential
diagnosis between MS and other inflammatory conditions like adult-onset postinfectious
neurological syndromes (PINS). The aim of this study was to investigate whether PINS
and MS have a shared genetic background using an updated polygenic risk scores.
Methods
Eighty-eight PINS patients have been consecutively recruited between 1996 and 2016
at Mondino Foundation of Pavia, diagnosed according to clinical, MRI and CSF findings
and followed-up for several years. Patients were typed using Illumina array, and genotypes
imputed using the 1000 Genomes Project reference panel. A weighted genetic risk score
(wGRS) has been calculated based on autosomal MS risk loci derived from large-scale
studies, and an HLA genetic burden (HLAGB) was also calculated on loci associated
to MS.
Results
PINS occurred as an episode of myelitis in 44% of patients, encephalomyelitis in 44%,
and encephalitis in remaining cases, with an involvement of peripheral nervous system
in 41% of patients. Mean age of onset was 50.1 years, and female:male ratio was 1.4.
Patients were followed-up for a mean of 7.2 years, and at last visit 55% had a low
disability grade (mRS 0–1). Disease was monophasic in 67% of patients, relapsing in
18% and chronic-progressive in 15%.
The wGRS of PINS cases was comparable to 370 healthy controls, while significantly
lower compared to 907 bout-onset MS (BOMS) cases (wGRS= 20.9 vs 21.2; p<0.0001). The difference was even larger for PINS with peripheral nervous system involvement
(wGRS=20.6) vs BOMS.
Conclusion
The distinction between MS and PINS is not easy to make in clinical practice. However,
our study shows that the new set of MS risk alleles does not confer increased susceptibility
to PINS. These data support the importance to discriminate these cases from MS with
pathophysiological and therapeutic implications.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Multiple Sclerosis and Related DisordersAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Acute disseminated encephalomyelitis: clinical features, HLA DRB1×1501, HLA DRB1×1503, HLA DQA1×0102, HLA DQB1×0602, and HLA DPA1×0301 allelic association study.Arq Neuropsiquiatr. 2009; 67: 643-651
- The spectrum of disseminated encephalomyelitis.Clin Neurol Neurosurg. 2006; 108: 295-310
- Acute disseminated encephalomyelitis, multiphasic disseminated encephalomyelitis and multiple sclerosis in children.Brain 123 Pt. 2000; 12: 2407-2422
- Next-generation genotype imputation service and methods.Nat Genet. 2016; 48: 1284-1287
- Integration of genetic risk factors into a clinical algorithm for multiple sclerosis susceptibility: a weighted genetic risk score.Lancet Neurol. 2009; 8: 1111-1119
- Improved whole-chromosome phasing for disease and population genetic studies.Nat Methods. 2013; 10: 5-6
- Acute disseminated encephalomyelitis in children: clinical features and HLA-DR linkage.Eur J Neurol. 2003; 10: 537-546
- Does HLA Class II haplotype play a role in adult acute disseminated encephalomyelitis? Preliminary findings from a Southern Italy hospital-based study.Arch Ital Biol. 2012; 150: 1-4
- Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility.Science. 2019; 365
- Low-Frequency and Rare-Coding Variation Contributes to Multiple Sclerosis Risk.Cell. 2018; 175 (1679-1687 e1677)
- Imputing amino acid polymorphisms in human leukocyte antigens.PLoS ONE. 2013; 8: e64683
- Genetic risk prediction in complex disease.Hum Mol Genet. 2011; 20: R182-R188
- Acute disseminated encephalomyelitis in 228 patients: a retrospective, multicenter US study.Neurology. 2016; 86: 2085-2093
- LDlink: a web-based application for exploring population-specific haplotype structure and linking correlated alleles of possible functional variants.Bioinformatics. 2015; 31: 3555-3557
- Postinfectious neurologic syndromes: a prospective cohort study.Neurology. 2013; 80: 882-889
- Postinfectious inflammatory disorders: subgroups based on prospective follow-up.Neurology. 2005; 65: 1057-1065
- Class II HLA interactions modulate genetic risk for multiple sclerosis.Nat Genet. 2015; 47: 1107-1113
- Molecular analysis of HLA class II-associated susceptibility to neuroinflammatory diseases in Korean children.J Korean Med Sci. 2004; 19: 426-430
- Acute disseminated encephalomyelitis: updates on an inflammatory CNS syndrome.Neurology. 2016; 87: S38-S45
- PLINK: a tool set for whole-genome association and population-based linkage analyses.Am J Hum Genet. 2007; 81: 559-575
- ROCR: visualizing classifier performance in R.Bioinformatics. 2005; 21: 3940-3941
- Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria.Lancet Neurol. 2018; 17: 162-173
- Multiple sclerosis.Lancet. 2018; 391: 1622-1636
- Risk genes associated with pediatric-onset MS but not with monophasic acquired CNS demyelination.Neurology. 2013; 81: 1996-2001
- Environmental and genetic factors in pediatric inflammatory demyelinating diseases.Neurology. 2016; 87: S20-S27
- Acute disseminated encephalomyelitis: current understanding and controversies.Semin Neurol. 2008; 28: 84-94
Article info
Publication history
Published online: June 23, 2020
Accepted:
June 21,
2020
Received in revised form:
May 22,
2020
Received:
March 27,
2020
Identification
Copyright
© 2020 Elsevier B.V. All rights reserved.
