Paolo Giordano1, Giuseppe Stefano Netti2, Luisa Santangelo1, Giuseppe Castellano3, Vincenza Carbone1, Diletta Domenica Torres1, Marida Martino1, Michela Sesta4, Franca Di Cuonzo5, Maria Chiara Resta5, Alberto Gaeta6, Leonardo Milella7, Maria Chironna8, Cinzia Germinario8, Gaia Scavia9, Loreto Gesualdo3, Mario Giordano10. 1. Pediatric Nephrology and Dialysis Unit, Pediatric Hospital "Giovanni XXIII", Bari, Italy. 2. Clinical Pathology Unit and Center for Molecular Medicine, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy. 3. Nephrology, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari "Aldo Moro", Bari, Italy. 4. Pediatric Neurology Unit, Pediatric Hospital "Giovanni XXIII", Bari, Italy. 5. Department of Neuroradiology, University of Bari "Aldo Moro", Bari, Italy. 6. Pediatric Radiology Unit, Pediatric Hospital "Giovanni XXIII", Bari, Italy. 7. Intensive Care Unit, Pediatric Hospital "Giovanni XXIII", Bari, Italy. 8. Department of Biomedical Science and Human Oncology, University of Bari "Aldo Moro", Bari, Italy. 9. Food Safety, Nutrition and Veterinary Public Health Department, National Institute of Health, Rome, Italy. 10. Pediatric Nephrology and Dialysis Unit, Pediatric Hospital "Giovanni XXIII", Bari, Italy. mariogiordanobari@fastwebnet.it.
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.
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 HUSpatients 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.
Entities:
Keywords:
Eculizumab; Hemolytic uremic syndrome; Magnetic resonance imaging; Neurological involvement
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