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A pediatric neurologic assessment score may drive the eculizumab-based treatment of Escherichia coli-related hemolytic uremic syndrome with neurological involvement

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Abstract

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.

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Author notes

  1. Paolo Giordano and Giuseppe Stefano Netti contributed equally to this work.

Authors and Affiliations

  1. Pediatric Nephrology and Dialysis Unit, Pediatric Hospital “Giovanni XXIII”, Bari, Italy

    Paolo Giordano, Luisa Santangelo, Vincenza Carbone, Diletta Domenica Torres, Marida Martino & Mario Giordano

  2. Clinical Pathology Unit and Center for Molecular Medicine, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy

    Giuseppe Stefano Netti

  3. Nephrology, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari “Aldo Moro”, Bari, Italy

    Giuseppe Castellano & Loreto Gesualdo

  4. Pediatric Neurology Unit, Pediatric Hospital “Giovanni XXIII”, Bari, Italy

    Michela Sesta

  5. Department of Neuroradiology, University of Bari “Aldo Moro”, Bari, Italy

    Franca Di Cuonzo & Maria Chiara Resta

  6. Pediatric Radiology Unit, Pediatric Hospital “Giovanni XXIII”, Bari, Italy

    Alberto Gaeta

  7. Intensive Care Unit, Pediatric Hospital “Giovanni XXIII”, Bari, Italy

    Leonardo Milella

  8. Department of Biomedical Science and Human Oncology, University of Bari “Aldo Moro”, Bari, Italy

    Maria Chironna & Cinzia Germinario

  9. Food Safety, Nutrition and Veterinary Public Health Department, National Institute of Health, Rome, Italy

    Gaia Scavia

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  1. Paolo Giordano
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  2. Giuseppe Stefano Netti
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Correspondence to Mario Giordano.

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Informed consent

We carried out a retrospective study based on registry data and no ethics approval was required. Nevertheless, all the children’s parents signed a written informed consent to collect their clinical data at time of hospital access.

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The authors declare that they have no conflict of interest.

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Giordano, P., Netti, G.S., Santangelo, L. et al. A pediatric neurologic assessment score may drive the eculizumab-based treatment of Escherichia coli-related hemolytic uremic syndrome with neurological involvement. Pediatr Nephrol 34, 517–527 (2019). https://doi.org/10.1007/s00467-018-4112-2

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