Pediatric Nephrology

, Volume 29, Issue 9, pp 1607–1615 | Cite as

Neurological involvement in children with E. coli O104:H4-induced hemolytic uremic syndrome

  • Angela Bauer
  • Sebastian Loos
  • Carola Wehrmann
  • Dirk Horstmann
  • Frank Donnerstag
  • Johanna Lemke
  • Georg Hillebrand
  • Ulrike Löbel
  • Lars Pape
  • Dieter Haffner
  • Carola Bindt
  • Thurid Ahlenstiel
  • Anette Melk
  • Anja Lehnhardt
  • Markus J. Kemper
  • Jun Oh
  • Hans Hartmann
Original Article

Abstract

Background

The aim of this study was to analyze the neurological involvement and outcome in pediatric patients with hemolytic uremic syndrome (HUS) during the 2011 epidemic caused by Escherichia coli O104:H4.

Methods

Clinical data and data from magnetic resonance imaging (MRI) scans and electroencephalography (EEG) during the acute phase of the disease and during follow-up at 3 and 6 months were analyzed in 50 patients. Twenty-five of these patients underwent neuropsychological testing (WISC IV) during follow-up.

Results

Neurological involvement (stupor or coma, seizures, visual disturbances, paresis, myocloni) was initially observed in 14/50 (28 %) patients. One patient died. EEG abnormalities were more frequent in patients with neurological involvement than in those without (12/14 vs. 13/25, respectively). Cranial MRI scans were analyzed in nine patients with neurological involvement, of whom five showed abnormal findings. At the 3- and 6-month follow-ups, EEG abnormalities were found in 14/40 (35 %) and 7/36 (19 %) patients, respectively, whereas 28/42 (67 %) and 17/39 (44 %) patients, respectively, complained about on-going reduced performance. Neuropsychological testing showed a slightly lower global intelligence quotient in patients with neurological involvement versus those without (113.4 ± 2.8 vs. 119.4 ± 1.8, respectively).

Conclusions

Neurological involvement was frequent in our cohort. Accordingly, the incidence of pathological EEG findings was high, even in patients without clinical signs of neurological involvement. Nevertheless, major neurological sequelae were rare, and neuropsychological outcome was favorable after 6 months.

Keywords

Hemolytic uremic syndrome E. coli O104:H4 Children Neurology Outcome 

Notes

Acknowledgments

We thank all participating patients and families. We particularly thank all of the nursing, medical staff and colleagues in our hospitals, who worked so hard during the outbreak.

Funding

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Conflicts of interest

Both centers, UKE and MHH, enrolled a total of six patients in a single-arm multicenter trial on eculizumab treatment, which is sponsored by Alexion Pharmaceuticals (Cheshire, CT). Data on the treatment effect in these patients will be published elsewhere.

References

  1. 1.
    Tarr PI, Gordon CA, Chandler WL (2005) Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet 365:1073–1086PubMedGoogle Scholar
  2. 2.
    Pennington H (2010) Escherichia coli O157. Lancet 376:1428–1435PubMedCrossRefGoogle Scholar
  3. 3.
    Scheiring J, Rosales A, Zimmerhackl LB (2010) Clinical practice. Today's understanding of the haemolytic uraemic syndrome. Eur J Pediatr 169:7–13PubMedCrossRefGoogle Scholar
  4. 4.
    Trachtman H, Austin C, Lewinski M, Stahl RA (2012) Renal and neurological involvement in typical Shiga toxin-associated HUS. Nat Rev Nephrol 8:658–669PubMedCrossRefGoogle Scholar
  5. 5.
    Meuth SG, Gobel K, Kanyshkova T, Ehling P, Ritter MA, Schwindt W, Bielaszewska M, Lebiedz P, Coulon P, Herrmann AM, Storck W, Kohmann D, Muthing J, Pavenstadt H, Kuhlmann T, Karch H, Peters G, Budde T, Wiendl H, Pape HC (2013) Thalamic involvement in patients with neurologic impairment due to Shiga toxin 2. Ann Neurol 73:419–429PubMedCrossRefGoogle Scholar
  6. 6.
    Eriksson KJ, Boyd SG, Tasker RC (2001) Acute neurology and neurophysiology of haemolytic-uraemic syndrome. Arch Dis Child 84:434–435PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Otukesh H, Hoseini R, Golnari P, Fereshtehnejad SM, Zamanfar D, Hooman N, Tabarroki A (2008) Short-term and long-term outcome of hemolytic uremic syndrome in Iranian children. J Nephrol 21:694–703PubMedGoogle Scholar
  8. 8.
    Rooney JC, Anderson RM, Hopkins IJ (1971) Clinical and pathologic aspects of central nervous system involvement in the haemolytic uraemic syndrome. Proc Aust Assoc Neurol 8:67–75PubMedGoogle Scholar
  9. 9.
    Sheth KJ, Swick HM, Haworth N (1986) Neurological involvement in hemolytic-uremic syndrome. Ann Neurol 19:90–93PubMedCrossRefGoogle Scholar
  10. 10.
    Hahn JS, Havens PL, Higgins JJ, O'Rourke PP, Estroff JA, Strand R (1989) Neurological complications of hemolytic-uremic syndrome. J Child Neurol 4:108–113PubMedCrossRefGoogle Scholar
  11. 11.
    Nathanson S, Kwon T, Elmaleh M, Charbit M, Launay EA, Harambat J, Brun M, Ranchin B, Bandin F, Cloarec S, Bourdat-Michel G, Pietrement C, Champion G, Ulinski T, Deschenes G (2010) Acute neurological involvement in diarrhea-associated hemolytic uremic syndrome. Clin J Am Soc Nephrol 5:1218–1228PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Schlieper A, Orrbine E, Wells GA, Clulow M, McLaine PN, Rowe PC (1999) Neuropsychological sequelae of haemolytic uraemic syndrome. Investigators of the HUS Cognitive Study. Arch Dis Child 80:214–220PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Gitiaux C, Krug P, Grevent D, Kossorotoff M, Poncet S, Eisermann M, Oualha M, Boddaert N, Salomon R, Desguerre I (2013) Brain magnetic resonance imaging pattern and outcome in children with haemolytic-uraemic syndrome and neurological impairment treated with eculizumab. Dev Med Child Neurol 55:758–765PubMedGoogle Scholar
  14. 14.
    Loos S, Ahlenstiel T, Kranz B, Staude H, Pape L, Hartel C, Vester U, Buchtala L, Benz K, Hoppe B, Beringer O, Krause M, Muller D, Pohl M, Lemke J, Hillebrand G, Kreuzer M, Konig J, Wigger M, Konrad M, Haffner D, Oh J, Kemper MJ (2012) An outbreak of Shiga toxin-producing Escherichia coli O104:H4 hemolytic uremic syndrome in Germany: Presentation and short-term outcome in children. Clin Infect Dis 55:753–759PubMedCrossRefGoogle Scholar
  15. 15.
    Kemper MJ (2012) Outbreak of hemolytic uremic syndrome caused by E. coli O104:H4 in Germany: a pediatric perspective. Pediatr Nephrol 27:161–164PubMedCrossRefGoogle Scholar
  16. 16.
    Ruggenenti P, Remuzzi G (2011) A German outbreak of haemolytic uraemic syndrome. Lancet 378:1057–1058PubMedCrossRefGoogle Scholar
  17. 17.
    Frank C, Werber D, Cramer JP, Askar M, Faber M, van der Heiden M, Bernard H, Fruth A, Prager R, Spode A, Wadl M, Zoufaly A, Jordan S, Kemper MJ, Follin P, Muller L, King LA, Rosner B, Buchholz U, Stark K, Krause G (2011) Epidemic profile of Shiga-toxin-producing Escherichia coli O104:H4 outbreak in Germany. N Engl J Med 365:1771–1780PubMedCrossRefGoogle Scholar
  18. 18.
    Bielaszewska M, Mellmann A, Zhang W, Kock R, Fruth A, Bauwens A, Peters G, Karch H (2011) Characterisation of the Escherichia coli strain associated with an outbreak of haemolytic uraemic syndrome in Germany, 2011: a microbiological study. Lancet Infect Dis 11:671–676PubMedCrossRefGoogle Scholar
  19. 19.
    Karch H, Denamur E, Dobrindt U, Finlay BB, Hengge R, Johannes L, Ron EZ, Tonjum T, Sansonetti PJ, Vicente M (2012) The enemy within us: lessons from the 2011 European Escherichia coli O104:H4 outbreak. EMBO Mol Med 4:841–848PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Magnus T, Rother J, Simova O, Meier-Cillien M, Repenthin J, Moller F, Gbadamosi J, Panzer U, Wengenroth M, Hagel C, Kluge S, Stahl RK, Wegscheider K, Urban P, Eckert B, Glatzel M, Fiehler J, Gerloff C (2012) The neurological syndrome in adults during the 2011 northern German E. coli serotype O104:H4 outbreak. Brain 135:1850–1859PubMedCrossRefGoogle Scholar
  21. 21.
    International Federation of Clinical Neurophysiology (1999) Recommendations for the practice of clinical neurophysiology: guidelines of the International Federation of Clinical Neurophysiology. Electroencephalogr Clin Neurophysiol Suppl 52:1–304Google Scholar
  22. 22.
    Donnerstag F, Ding X, Pape L, Bultmann E, Lucke T, Zajaczek J, Hoy L, Das AM, Lanfermann H, Ehrich J, Hartmann H (2012) Patterns in early diffusion-weighted MRI in children with haemolytic uraemic syndrome and CNS involvement. Eur Radiol 22:506–513PubMedCrossRefGoogle Scholar
  23. 23.
    Gallo EG, Gianantonio CA (1995) Extrarenal involvement in diarrhoea-associated haemolytic-uraemic syndrome. Pediatr Nephrol 9:117–119PubMedCrossRefGoogle Scholar
  24. 24.
    Gunzer F, Hennig-Pauka I, Waldmann KH, Sandhoff R, Grone HJ, Kreipe HH, Matussek A, Mengel M (2002) Gnotobiotic piglets develop thrombotic microangiopathy after oral infection with enterohemorrhagic Escherichia coli. Am J Clin Pathol 118:364–375PubMedCrossRefGoogle Scholar
  25. 25.
    Bale JF Jr, Brasher C, Siegler RL (1980) CNS manifestations of the hemolytic-uremic syndrome. Relationship to metabolic alterations and prognosis. Am J Dis Child 134:869–872PubMedCrossRefGoogle Scholar
  26. 26.
    Cimolai N, Morrison BJ, Carter JE (1992) Risk factors for the central nervous system manifestations of gastroenteritis-associated hemolytic-uremic syndrome. Pediatrics 90:616–621PubMedGoogle Scholar
  27. 27.
    Gerber A, Karch H, Allerberger F, Verweyen HM, Zimmerhackl LB (2002) Clinical course and the role of shiga toxin-producing Escherichia coli infection in the hemolytic-uremic syndrome in pediatric patients, 1997–2000, in Germany and Austria: a prospective study. J Infect Dis 186:493–500PubMedCrossRefGoogle Scholar
  28. 28.
    Scheiring J, Andreoli SP, Zimmerhackl LB (2008) Treatment and outcome of Shiga-toxin-associated hemolytic uremic syndrome (HUS). Pediatr Nephrol 23:1749–1760PubMedCrossRefGoogle Scholar
  29. 29.
    Weissenborn K, Donnerstag F, Kielstein JT, Heeren M, Worthmann H, Hecker H, Schmitt R, Schiffer M, Pasedag T, Schuppner R, Tryc AB, Raab P, Hartmann H, Ding XQ, Hafer C, Menne J, Schmidt BM, Bultmann E, Haller H, Dengler R, Lanfermann H, Giesemann AM (2012) Neurologic manifestations of E. coli infection-induced hemolytic-uremic syndrome in adults. Neurology 79:1466–1473PubMedCrossRefGoogle Scholar
  30. 30.
    Schlieper A, Rowe PC, Orrbine E, Zoubek M, Clark W, Wolfish N, McLaine PN (1992) Sequelae of haemolytic uraemic syndrome. Arch Dis Child 67:930–934PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© IPNA 2014

Authors and Affiliations

  • Angela Bauer
    • 1
  • Sebastian Loos
    • 1
  • Carola Wehrmann
    • 3
  • Dirk Horstmann
    • 2
  • Frank Donnerstag
    • 4
  • Johanna Lemke
    • 1
  • Georg Hillebrand
    • 1
  • Ulrike Löbel
    • 5
  • Lars Pape
    • 2
  • Dieter Haffner
    • 2
  • Carola Bindt
    • 3
  • Thurid Ahlenstiel
    • 2
  • Anette Melk
    • 2
  • Anja Lehnhardt
    • 1
  • Markus J. Kemper
    • 1
  • Jun Oh
    • 1
    • 6
  • Hans Hartmann
    • 2
  1. 1.Department of PediatricsUniversity Medical Center HamburgHamburgGermany
  2. 2.Department of Pediatric Kidney, Liver, and Metabolic DiseasesHannover Medical SchoolHannoverGermany
  3. 3.Department of Child and Adolescent Psychiatry and PsychotherapyUniversity Medical Center HamburgHamburgGermany
  4. 4.Institute of Diagnostic and Therapeutic Neuroradiology, Hannover Medical SchoolHannoverGermany
  5. 5.Department of NeuroradiologyUniversity Medical Center HamburgHamburgGermany
  6. 6.Pediatric Nephrology, Department of PediatricsUniversity Medical Center HamburgHamburgGermany

Personalised recommendations