Sine causa tetraparesis: A pilot study on its possible relationship with interferon signature analysis and Aicardi Goutières syndrome related genes analysis

AGS study group

Research output: Contribution to journalArticle

Abstract

Tetraparesis is usually due to cerebral palsy (CP), inborn errors of metabolism, neurogenetic disorders and spinal cord lesions. However, literature data reported that about 10% of children with tetraparesis show a negative/non-specific neuroradiological findings without a specific etiological cause. Aicardi Goutières Syndrome (AGS) is a genetic encephalopathy that may cause tetraparesis. Interferon signature is a reliable biomarker for AGS and could be performed in sine-causa tetraparesis. The aim of the study was to examine the type I interferon signature and AGS related-genes in children with sine causa tetraparesis, to look for misdiagnosed AGS. A secondary aim was to determine which aspects of the patient history, clinical picture and brain imaging best characterize tetraparesis due to an interferonopathy.Seven out of 78 patients affected by tetraparesis, characterized by unremarkable pre-peri-postnatal history and normal/non-specific brain magnetic resonance imaging (MRI) were selected and underwent anamnestic data collection, clinical examination, brain imaging review, peripheral blood interferon signature and AGS-related genes analysis.At our evaluation time (mean age of 11.9 years), all the 7 patients showed spastic-dystonic tetraparesis. At clinical onset brain MRI was normal in 4 and with non-specific abnormalities in 3; at follow-up 3 patients presented with new white-matter lesions, associated with brain calcification in 1 case. Interferon signature was elevated in one subject who presented also a mutation of the IFIH1 gene.AGS should be considered in sine-causa tetraparesis. Core features of interferonopathy-related tetraparesis are: onset during first year of life, psychomotor regression with tetraparesis evolution, brain white-matter lesions with late calcifications. A positive interferon signature may be a helpful marker to select patients with spastic tetraparesis who should undergo genetic analysis for AGS.

Original languageEnglish
Pages (from-to)e13893
JournalMedicine
Volume97
Issue number52
DOIs
Publication statusPublished - Dec 2018

Fingerprint

Aicardi Syndrome
Interferons
Genes
Muscle Spasticity
Brain
Neuroimaging
Magnetic Resonance Imaging
Inborn Errors Metabolism
Interferon Type I
Spinal Cord Diseases
Brain Diseases
Cerebral Palsy
Diagnostic Errors
Biomarkers
History
Mutation

Keywords

  • Adolescent
  • Autoimmune Diseases of the Nervous System/complications
  • Biomarkers
  • Brain/diagnostic imaging
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Interferon Type I/biosynthesis
  • Magnetic Resonance Imaging
  • Male
  • Nervous System Malformations/complications
  • Paresis/etiology
  • Pilot Projects
  • Young Adult

Cite this

Sine causa tetraparesis : A pilot study on its possible relationship with interferon signature analysis and Aicardi Goutières syndrome related genes analysis. / AGS study group.

In: Medicine, Vol. 97, No. 52, 12.2018, p. e13893.

Research output: Contribution to journalArticle

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title = "Sine causa tetraparesis: A pilot study on its possible relationship with interferon signature analysis and Aicardi Gouti{\`e}res syndrome related genes analysis",
abstract = "Tetraparesis is usually due to cerebral palsy (CP), inborn errors of metabolism, neurogenetic disorders and spinal cord lesions. However, literature data reported that about 10{\%} of children with tetraparesis show a negative/non-specific neuroradiological findings without a specific etiological cause. Aicardi Gouti{\`e}res Syndrome (AGS) is a genetic encephalopathy that may cause tetraparesis. Interferon signature is a reliable biomarker for AGS and could be performed in sine-causa tetraparesis. The aim of the study was to examine the type I interferon signature and AGS related-genes in children with sine causa tetraparesis, to look for misdiagnosed AGS. A secondary aim was to determine which aspects of the patient history, clinical picture and brain imaging best characterize tetraparesis due to an interferonopathy.Seven out of 78 patients affected by tetraparesis, characterized by unremarkable pre-peri-postnatal history and normal/non-specific brain magnetic resonance imaging (MRI) were selected and underwent anamnestic data collection, clinical examination, brain imaging review, peripheral blood interferon signature and AGS-related genes analysis.At our evaluation time (mean age of 11.9 years), all the 7 patients showed spastic-dystonic tetraparesis. At clinical onset brain MRI was normal in 4 and with non-specific abnormalities in 3; at follow-up 3 patients presented with new white-matter lesions, associated with brain calcification in 1 case. Interferon signature was elevated in one subject who presented also a mutation of the IFIH1 gene.AGS should be considered in sine-causa tetraparesis. Core features of interferonopathy-related tetraparesis are: onset during first year of life, psychomotor regression with tetraparesis evolution, brain white-matter lesions with late calcifications. A positive interferon signature may be a helpful marker to select patients with spastic tetraparesis who should undergo genetic analysis for AGS.",
keywords = "Adolescent, Autoimmune Diseases of the Nervous System/complications, Biomarkers, Brain/diagnostic imaging, Child, Child, Preschool, Female, Humans, Interferon Type I/biosynthesis, Magnetic Resonance Imaging, Male, Nervous System Malformations/complications, Paresis/etiology, Pilot Projects, Young Adult",
author = "{AGS study group} and Jessica Galli and Francesco Gavazzi and {De Simone}, Micaela and Silvia Giliani and Jessica Garau and Marialuisa Valente and Donatella Vairo and Marco Cattalini and Marzia Mortilla and Laura Andreoli and Raffaele Badolato and Marika Bianchi and Nice Carabellese and Cristina Cereda and Rosalba Ferraro and Fabio Facchetti and Micaela Fredi and Giulio Gualdi and Luisa Lorenzi and Antonella Meini and Simona Orcesi and Angela Tincani and Alessandra Zanola and Gillian Rice and Elisa Fazzi",
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T2 - A pilot study on its possible relationship with interferon signature analysis and Aicardi Goutières syndrome related genes analysis

AU - AGS study group

AU - Galli, Jessica

AU - Gavazzi, Francesco

AU - De Simone, Micaela

AU - Giliani, Silvia

AU - Garau, Jessica

AU - Valente, Marialuisa

AU - Vairo, Donatella

AU - Cattalini, Marco

AU - Mortilla, Marzia

AU - Andreoli, Laura

AU - Badolato, Raffaele

AU - Bianchi, Marika

AU - Carabellese, Nice

AU - Cereda, Cristina

AU - Ferraro, Rosalba

AU - Facchetti, Fabio

AU - Fredi, Micaela

AU - Gualdi, Giulio

AU - Lorenzi, Luisa

AU - Meini, Antonella

AU - Orcesi, Simona

AU - Tincani, Angela

AU - Zanola, Alessandra

AU - Rice, Gillian

AU - Fazzi, Elisa

PY - 2018/12

Y1 - 2018/12

N2 - Tetraparesis is usually due to cerebral palsy (CP), inborn errors of metabolism, neurogenetic disorders and spinal cord lesions. However, literature data reported that about 10% of children with tetraparesis show a negative/non-specific neuroradiological findings without a specific etiological cause. Aicardi Goutières Syndrome (AGS) is a genetic encephalopathy that may cause tetraparesis. Interferon signature is a reliable biomarker for AGS and could be performed in sine-causa tetraparesis. The aim of the study was to examine the type I interferon signature and AGS related-genes in children with sine causa tetraparesis, to look for misdiagnosed AGS. A secondary aim was to determine which aspects of the patient history, clinical picture and brain imaging best characterize tetraparesis due to an interferonopathy.Seven out of 78 patients affected by tetraparesis, characterized by unremarkable pre-peri-postnatal history and normal/non-specific brain magnetic resonance imaging (MRI) were selected and underwent anamnestic data collection, clinical examination, brain imaging review, peripheral blood interferon signature and AGS-related genes analysis.At our evaluation time (mean age of 11.9 years), all the 7 patients showed spastic-dystonic tetraparesis. At clinical onset brain MRI was normal in 4 and with non-specific abnormalities in 3; at follow-up 3 patients presented with new white-matter lesions, associated with brain calcification in 1 case. Interferon signature was elevated in one subject who presented also a mutation of the IFIH1 gene.AGS should be considered in sine-causa tetraparesis. Core features of interferonopathy-related tetraparesis are: onset during first year of life, psychomotor regression with tetraparesis evolution, brain white-matter lesions with late calcifications. A positive interferon signature may be a helpful marker to select patients with spastic tetraparesis who should undergo genetic analysis for AGS.

AB - Tetraparesis is usually due to cerebral palsy (CP), inborn errors of metabolism, neurogenetic disorders and spinal cord lesions. However, literature data reported that about 10% of children with tetraparesis show a negative/non-specific neuroradiological findings without a specific etiological cause. Aicardi Goutières Syndrome (AGS) is a genetic encephalopathy that may cause tetraparesis. Interferon signature is a reliable biomarker for AGS and could be performed in sine-causa tetraparesis. The aim of the study was to examine the type I interferon signature and AGS related-genes in children with sine causa tetraparesis, to look for misdiagnosed AGS. A secondary aim was to determine which aspects of the patient history, clinical picture and brain imaging best characterize tetraparesis due to an interferonopathy.Seven out of 78 patients affected by tetraparesis, characterized by unremarkable pre-peri-postnatal history and normal/non-specific brain magnetic resonance imaging (MRI) were selected and underwent anamnestic data collection, clinical examination, brain imaging review, peripheral blood interferon signature and AGS-related genes analysis.At our evaluation time (mean age of 11.9 years), all the 7 patients showed spastic-dystonic tetraparesis. At clinical onset brain MRI was normal in 4 and with non-specific abnormalities in 3; at follow-up 3 patients presented with new white-matter lesions, associated with brain calcification in 1 case. Interferon signature was elevated in one subject who presented also a mutation of the IFIH1 gene.AGS should be considered in sine-causa tetraparesis. Core features of interferonopathy-related tetraparesis are: onset during first year of life, psychomotor regression with tetraparesis evolution, brain white-matter lesions with late calcifications. A positive interferon signature may be a helpful marker to select patients with spastic tetraparesis who should undergo genetic analysis for AGS.

KW - Adolescent

KW - Autoimmune Diseases of the Nervous System/complications

KW - Biomarkers

KW - Brain/diagnostic imaging

KW - Child

KW - Child, Preschool

KW - Female

KW - Humans

KW - Interferon Type I/biosynthesis

KW - Magnetic Resonance Imaging

KW - Male

KW - Nervous System Malformations/complications

KW - Paresis/etiology

KW - Pilot Projects

KW - Young Adult

U2 - 10.1097/MD.0000000000013893

DO - 10.1097/MD.0000000000013893

M3 - Article

C2 - 30593198

VL - 97

SP - e13893

JO - Medicine; analytical reviews of general medicine, neurology, psychiatry, dermatology, and pediatries

JF - Medicine; analytical reviews of general medicine, neurology, psychiatry, dermatology, and pediatries

SN - 0025-7974

IS - 52

ER -