Frequency and spectrum of central nervous system involvement in 193 children with haemophagocytic lymphohistiocytosis.

TY - JOUR

T1 - Frequency and spectrum of central nervous system involvement in 193 children with haemophagocytic lymphohistiocytosis.

AU - Horne, AnnaCarin

AU - Trottestam, Helena

AU - Aricò, Maurizio

AU - Egeler, R Maarten

AU - Filipovich, Alexandra H

AU - Gadner, Helmut

AU - Imashuku, Shinsaku

AU - Ladisch, Stephan

AU - Webb, David

AU - Janka-Schaub, Gritta

AU - Henter, Jan-Inge

PY - 2008

Y1 - 2008

N2 - Haemophagocytic lymphohistiocytosis (HLH) may cause meningoencephalitis and significant neurological sequelae. We examined the relationship between neurological symptoms and cerebrospinal fluid (CSF) at diagnosis, and long-term outcome, in all children enroled in the HLH-94-study prior to July 1, 2003, for whom information on CSF at diagnosis was available (n = 193). Patients were divided into four groups: (i) normal CSF (cells/protein) and no neurological symptoms (n = 71); (ii) normal CSF but neurological symptoms (n = 21); (iii) abnormal CSF but no symptoms (n = 50); and (iv) abnormal CSF with neurological symptoms (n = 51). At diagnosis, neurological symptoms were reported in 72/193 (37%) (seizures = 23); abnormal CSF in 101/193 (52%), and either or both in 122/193 (63%). Altogether 16/107 (15%) survivors had neurological sequelae at follow-up (median 5.3 years). Multivariate hazard ratios (HR) for mortality were 0.98 [95% confidence interval (CI) = 0.42-2.31], 1.52 (0.82-2.82) and 2.05 (1.13-3.72) for groups 2-4, compared with group 1. Moreover, sequelae were more frequent in group 4 (7/21, 33%) compared to groups 1-3 (9/86, 10%) (P = 0.015). Patients with abnormal CSF at diagnosis had significantly increased mortality [HR = 1.78 (95% CI = 1.08-2.92), P = 0.023]. Thus, a substantial proportion of HLH survivors suffer neurological sequelae, and children with abnormal CSF have increased risk of mortality and neurological sequelae. Prompt treatment of HLH at onset or relapse may reduce these complications.

AB - Haemophagocytic lymphohistiocytosis (HLH) may cause meningoencephalitis and significant neurological sequelae. We examined the relationship between neurological symptoms and cerebrospinal fluid (CSF) at diagnosis, and long-term outcome, in all children enroled in the HLH-94-study prior to July 1, 2003, for whom information on CSF at diagnosis was available (n = 193). Patients were divided into four groups: (i) normal CSF (cells/protein) and no neurological symptoms (n = 71); (ii) normal CSF but neurological symptoms (n = 21); (iii) abnormal CSF but no symptoms (n = 50); and (iv) abnormal CSF with neurological symptoms (n = 51). At diagnosis, neurological symptoms were reported in 72/193 (37%) (seizures = 23); abnormal CSF in 101/193 (52%), and either or both in 122/193 (63%). Altogether 16/107 (15%) survivors had neurological sequelae at follow-up (median 5.3 years). Multivariate hazard ratios (HR) for mortality were 0.98 [95% confidence interval (CI) = 0.42-2.31], 1.52 (0.82-2.82) and 2.05 (1.13-3.72) for groups 2-4, compared with group 1. Moreover, sequelae were more frequent in group 4 (7/21, 33%) compared to groups 1-3 (9/86, 10%) (P = 0.015). Patients with abnormal CSF at diagnosis had significantly increased mortality [HR = 1.78 (95% CI = 1.08-2.92), P = 0.023]. Thus, a substantial proportion of HLH survivors suffer neurological sequelae, and children with abnormal CSF have increased risk of mortality and neurological sequelae. Prompt treatment of HLH at onset or relapse may reduce these complications.

M3 - SCORING: Zeitschriftenaufsatz

VL - 140

SP - 327

EP - 335

JO - BRIT J HAEMATOL

JF - BRIT J HAEMATOL

SN - 0007-1048

IS - 3

M1 - 3

ER -