A pediatric neurologic assessment score may drive the eculizumab-based treatment of Escherichia coli-related hemolytic uremic syndrome with neurological involvement.
Antibodies, Monoclonal, Humanized
/ therapeutic use
Brain
/ diagnostic imaging
Brain Diseases
/ diagnosis
Child, Preschool
Clinical Decision-Making
Complement Inactivating Agents
/ therapeutic use
Electroencephalography
Feasibility Studies
Female
Hemolytic-Uremic Syndrome
/ complications
Humans
Infant
Italy
/ epidemiology
Magnetic Resonance Imaging
Male
Neuroimaging
/ methods
Patient Selection
Retrospective Studies
Shiga-Toxigenic Escherichia coli
/ isolation & purification
Tomography, X-Ray Computed
Treatment Outcome
Eculizumab
Hemolytic uremic syndrome
Magnetic resonance imaging
Neurological involvement
Journal
Pediatric nephrology (Berlin, Germany)
ISSN: 1432-198X
Titre abrégé: Pediatr Nephrol
Pays: Germany
ID NLM: 8708728
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
14
03
2018
accepted:
04
10
2018
revised:
02
10
2018
pubmed:
27
10
2018
medline:
6
5
2020
entrez:
27
10
2018
Statut:
ppublish
Résumé
Thrombotic microangiopathy (TMA) is a clinical syndrome encompassing a large group of rare but severe disorders including thrombotic thrombocytopenic purpura (TTP) and both typical and atypical forms of hemolytic uremic syndrome (HUS). The key role of the complement system is well known in TTP and atypical HUS, but recent reports describe its involvement in the pathogenesis of HUS secondary to gastrointestinal infections due to Shiga toxin-producing Escherichia coli (STEC). TMA mainly affects the kidney, but extra-renal complications are frequently described. The involvement of the central nervous system (CNS) represents often a life-threatening condition and it can result in serious long-term disability in HUS patients who overcome the acute phase of illness. In the present study, we retrospectively analyzed a pediatric cohort of a single tertiary pediatric hospital in Southern Italy, in which this complication occurred in 12/54 children (22% of cases), of whom five with severe neurological involvement had been successfully treated with eculizumab. The great clinical variability of brain injury in our cohort has led us to retrospectively build a "neurological score" useful to assess the clinical severity of neurologic involvement. Subjects with higher neurologic score due to the most severe CNS involvement resulted in the group of patients early treated with eculizumab, obtaining a good clinical response (four out five patients). In conclusion, the early treatment with eculizumab in children with severe neurological involvement during STEC-HUS was associated with complete regression of both acute kidney injury (AKI) and neurological lesions observed at magnetic resonance imaging (MRI). A "neurological score" may be a useful tool to drive the early treatment of CNS complications in STEC-HUS with eculizumab, although future perspective controlled studies are urgently needed to validate this therapeutic approach.
Sections du résumé
BACKGROUND
Thrombotic microangiopathy (TMA) is a clinical syndrome encompassing a large group of rare but severe disorders including thrombotic thrombocytopenic purpura (TTP) and both typical and atypical forms of hemolytic uremic syndrome (HUS). The key role of the complement system is well known in TTP and atypical HUS, but recent reports describe its involvement in the pathogenesis of HUS secondary to gastrointestinal infections due to Shiga toxin-producing Escherichia coli (STEC).
METHODS
TMA mainly affects the kidney, but extra-renal complications are frequently described. The involvement of the central nervous system (CNS) represents often a life-threatening condition and it can result in serious long-term disability in HUS patients who overcome the acute phase of illness. In the present study, we retrospectively analyzed a pediatric cohort of a single tertiary pediatric hospital in Southern Italy, in which this complication occurred in 12/54 children (22% of cases), of whom five with severe neurological involvement had been successfully treated with eculizumab.
RESULTS
The great clinical variability of brain injury in our cohort has led us to retrospectively build a "neurological score" useful to assess the clinical severity of neurologic involvement. Subjects with higher neurologic score due to the most severe CNS involvement resulted in the group of patients early treated with eculizumab, obtaining a good clinical response (four out five patients). In conclusion, the early treatment with eculizumab in children with severe neurological involvement during STEC-HUS was associated with complete regression of both acute kidney injury (AKI) and neurological lesions observed at magnetic resonance imaging (MRI).
CONCLUSIONS
A "neurological score" may be a useful tool to drive the early treatment of CNS complications in STEC-HUS with eculizumab, although future perspective controlled studies are urgently needed to validate this therapeutic approach.
Identifiants
pubmed: 30362078
doi: 10.1007/s00467-018-4112-2
pii: 10.1007/s00467-018-4112-2
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Complement Inactivating Agents
0
eculizumab
A3ULP0F556
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
517-527Références
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