Spectrum of neuroradiological manifestations in primary hemophagocytic lymphohistiocytosis: a comparative study of EBV-induced versus non-EBV-induced forms in 75 genetically confirmed pediatric cases.
Basal ganglia
Epstein-Barr virus infections
Hemophagocytic lymphohistiocytosis
Magnetic resonance imaging
Mutation
Journal
European radiology
ISSN: 1432-1084
Titre abrégé: Eur Radiol
Pays: Germany
ID NLM: 9114774
Informations de publication
Date de publication:
Oct 2023
Oct 2023
Historique:
received:
03
07
2022
accepted:
09
02
2023
revised:
23
12
2022
medline:
21
9
2023
pubmed:
12
5
2023
entrez:
12
5
2023
Statut:
ppublish
Résumé
Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening condition affecting young children. It is potentially triggered by Epstein-Barr virus (EBV). This study describes the neuroradiological features observed in 75 children with genetically confirmed primary HLH, comparing EBV-induced with non-EBV-induced HLH forms. Brain MRIs between 2007 and 2021 from 75 children with HLH according to the 2004 Histiocyte Society criteria and with a confirmed HLH-related mutation, were retrospectively reviewed by two pediatric neuroradiologists blinded to EBV status and to mutation status. At diagnosis, 17 children with EBV viremia above a threshold of 1000 copies/mL were included in the EBV-induced HLH group. The remaining 58 patients were included in the non-EBV-induced HLH group. Of the 75 children initially included, 21 had abnormal MRI (21/75 (28%); 9/17 in the EBV-induced HLH group and 12/58 in the non-EBV-induced HLH group). All patients with abnormal MRI had neurological symptoms. Abnormal MRIs showed white matter lesions; the posterior fossa was affected in all but one case. There was no significant difference between groups regarding the localization or morphology of white matter lesions. The striatum was more frequently affected in the EBV-induced HLH group (8/9 (89%) versus 1/12 (8%), p = 0.00037). All lesions, whether in the white matter or in the basal ganglia, presented increased ADC values on diffusion weighted imaging (DWI). In this study of 75 children with genetically confirmed HLH, only children with neurological signs had abnormal brain MRI. Bilateral striatum involvement suggested an EBV-induced form of HLH. • In children with genetically proven HLH, only those with neurological signs did have brain abnormalities at MRI. • All patients with abnormal brain MRI had multiple white matter lesions with increased ADC values, including in the posterior fossa in almost all cases. • Basal ganglia and in particular the striatum were bilaterally and symmetrically affected in almost all EBV-induced HLH patients, in contrast to the non-EBV-induced HLH patients.
Identifiants
pubmed: 37171488
doi: 10.1007/s00330-023-09649-2
pii: 10.1007/s00330-023-09649-2
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7149-7159Informations de copyright
© 2023. The Author(s), under exclusive licence to European Society of Radiology.
Références
Esteban YM, de Jong JLO, Tesher MS (2017) An overview of hemophagocytic lymphohistiocytosis. Pediatr Ann 46:e309–e313. https://doi.org/10.3928/19382359-20170717-01
doi: 10.3928/19382359-20170717-01
pubmed: 28806468
Skinner J, Yankey B, Shelton BK (2019) Hemophagocytic lymphohistiocytosis. AACN Adv. Crit Care 30:151–164. https://doi.org/10.4037/aacnacc2019463
doi: 10.4037/aacnacc2019463
Gonzalez F, Vincent F, Cohen Y (2009) Infectious macrophagic activation syndrome: etiologies and management. Reanimation 18:284–290. https://doi.org/10.1016/j.reaurg.2009.03.002
doi: 10.1016/j.reaurg.2009.03.002
Germi R, Baccard M, Seigneyrin JM et al (2011) Epstein-Barr virus infections. In: EM-Consulte. https://www.em-consulte.com/article/663237/infections-a-virus-epstein-barr . Accessed 19 Aug 2021
Kamila Ż-W, Teresa R, Patrycja M-G, Andrzej S (2015) Neurological presentation of hemophagocytic lymphohistiocytosis. Neurol Neurochir Pol 49:329–331. https://doi.org/10.1016/j.pjnns.2015.07.001
doi: 10.1016/j.pjnns.2015.07.001
pubmed: 26377985
Cheng H, Chen D, Peng X et al (2020) Clinical characteristics of Epstein-Barr virus infection in the pediatric nervous system. BMC Infect Dis 20:886. https://doi.org/10.1186/s12879-020-05623-1
doi: 10.1186/s12879-020-05623-1
pubmed: 33238935
pmcid: 7691062
Deiva K, Mahlaoui N, Beaudonnet F et al (2012) CNS involvement at the onset of primary hemophagocytic lymphohistiocytosis. Neurology 78:1150–1156. https://doi.org/10.1212/WNL.0b013e31824f800a
doi: 10.1212/WNL.0b013e31824f800a
pubmed: 22422896
Horne A, Trottestam H, Aricò M et al (2008) Frequency and spectrum of central nervous system involvement in 193 children with haemophagocytic lymphohistiocytosis. Br J Haematol 140:327–335. https://doi.org/10.1111/j.1365-2141.2007.06922.x
doi: 10.1111/j.1365-2141.2007.06922.x
pubmed: 18076710
Boutin B, Routon MC, Rocchiccioli F et al (1988) Peripheral neuropathy associated with erythrophagocytic lymphohistiocytosis. J Neurol Neurosurg Psychiatry 51:291–294. https://doi.org/10.1136/jnnp.51.2.291
doi: 10.1136/jnnp.51.2.291
pubmed: 3346698
pmcid: 1031548
Blincoe A, Heeg M, Campbell PK et al (2020) Neuroinflammatory disease as an isolated manifestation of hemophagocytic lymphohistiocytosis. J Clin Immunol 40:901–916. https://doi.org/10.1007/s10875-020-00814-6
doi: 10.1007/s10875-020-00814-6
pubmed: 32638196
Benson LA, Li H, Henderson LA et al (2019) Pediatric CNS-isolated hemophagocytic lymphohistiocytosis. Neurol Neuroimmunol Neuroinflamm 6:e560. https://doi.org/10.1212/NXI.0000000000000560
Ozgen B, Karli-Oguz K, Sarikaya B et al (2006) Diffusion-weighted cranial MR imaging findings in a patient with hemophagocytic syndrome. AJNR Am J Neuroradiol 27:1312–1314
pubmed: 16775287
pmcid: 8133932
Henter JI, Nennesmo I (1997) Neuropathologic findings and neurologic symptoms in twenty-three children with hemophagocytic lymphohistiocytosis. J Pediatr 130:358–365. https://doi.org/10.1016/s0022-3476(97)70196-3
doi: 10.1016/s0022-3476(97)70196-3
pubmed: 9063409
Tong KA, Ashwal S, Obenaus A et al (2008) Susceptibility-weighted MR imaging: a review of clinical applications in children. AJNR Am J Neuroradiol 29:9–17. https://doi.org/10.3174/ajnr.A0786
doi: 10.3174/ajnr.A0786
pubmed: 17925363
pmcid: 8119104
Pak N, Selehnia A, Hunfeld MAW et al (2021) Atypical neuroimaging characteristics of hemophagocytic lymphohistiocytosis in infants: a case series of hemorrhagic brain lesions in the deep grey matter. Neuroradiology 63:285–288. https://doi.org/10.1007/s00234-020-02595-6
doi: 10.1007/s00234-020-02595-6
pubmed: 33156371
Forbes KPN, Collie DA, Parker A (2000) CNS involvement of virus-associated hemophagocytic syndrome: MR imaging appearance. AJNR Am J Neuroradiol 21:1248–1250
pubmed: 10954276
pmcid: 8174911
Pachlopnik Schmid J, Canioni D, Moshous D et al (2011) Clinical similarities and differences of patients with X-linked lymphoproliferative syndrome type 1 (XLP-1/SAP deficiency) versus type 2 (XLP-2/XIAP deficiency). Blood 117:1522–1529. https://doi.org/10.1182/blood-2010-07-298372
doi: 10.1182/blood-2010-07-298372
pubmed: 21119115
Nehme N, Pachlopnik-Schmid J, Basile G de S (2010) Hemophagocytic syndromes of genetic origin. Rev Med Genet Hum 1:34-44
Koeller KK, Shih RY (2017) Viral and prion infections of the central nervous system: radiologic-pathologic correlation: from the radiologic pathology archives. Radiographics 37:199–233. https://doi.org/10.1148/rg.2017160149
doi: 10.1148/rg.2017160149
pubmed: 28076019
Pinto J, Carvalho S, Pereira C et al (2015) A case of Epstein-Barr encephalitis with some curiosities. Neuroradiol J 28:559–561. https://doi.org/10.1177/1971400915602802
doi: 10.1177/1971400915602802
pubmed: 26481185
pmcid: 4757136
Whitehead MT, Lee B, Gropman A (2016) Lesional perfusion abnormalities in Leigh disease demonstrated by arterial spin labeling correlate with disease activity. Pediatr Radiol 46:1309–1316. https://doi.org/10.1007/s00247-016-3616-9
doi: 10.1007/s00247-016-3616-9
pubmed: 27043731
Alves CAPF, Teixeira SR, Martin-Saavedra JS et al (2020) Pediatric Leigh syndrome: neuroimaging features and genetic correlations. Ann Neurol 88:218–232. https://doi.org/10.1002/ana.25789
doi: 10.1002/ana.25789
pubmed: 32445240
Loiselet K, Ruzzenente B, Roux C-J et al (2021) Cerebral blood flow and acute episodes of Leigh syndrome in neurometabolic disorders. Dev Med Child Neurol 63:705–711. https://doi.org/10.1111/dmcn.14814
doi: 10.1111/dmcn.14814
pubmed: 33511646
Ma W, Li XJ, Li W et al (2021) MRI findings of central nervous system involvement in children with haemophagocytic lymphohistiocytosis: correlation with clinical biochemical tests. Clin Radiol 76:159.e9-159.e17. https://doi.org/10.1016/j.crad.2020.09.009
doi: 10.1016/j.crad.2020.09.009
pubmed: 33036779