title: CNS involvement at the onset of primary hemophagocytic lymphohistiocytosis.
abstract: OBJECTIVE
  To differentiate onset of CNS involvement in primary hemophagocytic lymphohistiocytosis (HLH) from that of other CNS inflammatory diseases and to identify early symptoms linked to abnormal cognitive outcome.
  
  
  METHODS
  Forty-six children with primary HLH who had neurologic evaluation within 2 weeks and brain MRI within 6 months of diagnosis were included. Initial symptoms, CSF study, brain MRI, and neurologic outcome were assessed. Brain MRIs were compared with those of 44 children with acute disseminated encephalomyelitis (ADEM).
  
  
  RESULTS
  At disease onset, 29 children (63%) had neurologic symptoms and 7 (15%) had microcephaly. Twenty-three (50%) children had abnormal CSF study, but only 15 (33%) had abnormal brain MRI. The latter showed that patients with HLH, unlike patients with ADEM, had symmetric periventricular lesions, without thalamic and brainstem involvement and with infrequent hyposignal intensity on T1. At the end of follow-up (3.6 ± 3.6 years), 17 of the 28 (61%) surviving patients had normal neurologic status, 5 (18%) had a severe neurologic outcome, and 6 (21%) had mild cognitive difficulties. Abnormal neurologic outcome was not influenced by age or type of genetic defect, but by the presence of neurologic symptoms, MRI lesions, or abnormal CSF study at onset. Early clinical and MRI symptoms may regress after treatment.
  
  
  CONCLUSIONS
  Neurologic symptoms are frequent at the onset of primary HLH and are mostly associated with abnormal CSF findings, but with normal brain MRI. In cases of abnormal brain MRI, the observed lesions differ from those of ADEM.
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Pediatric Neurology Department, National Referral Center for Neuro-Inflammatory Diseases in Children, and University Paris Sud, Le Kremlin-Bicêtre, Paris, France. kumaran.deiva@bct.aphp.fr
authors.forename: K
authors.initials: K
authors.lastname: Deiva
authors.forename: N
authors.initials: N
authors.lastname: Mahlaoui
authors.forename: F
authors.initials: F
authors.lastname: Beaudonnet
authors.forename: G
authors.initials: G
authors.lastname: de Saint Basile
authors.forename: G
authors.initials: G
authors.lastname: Caridade
authors.forename: D
authors.initials: D
authors.lastname: Moshous
authors.forename: Y
authors.initials: Y
authors.lastname: Mikaeloff
authors.forename: S
authors.initials: S
authors.lastname: Blanche
authors.forename: A
authors.initials: A
authors.lastname: Fischer
authors.forename: M
authors.initials: M
authors.lastname: Tardieu
mesh_terms: D000293:Adolescent; D001921:Brain / Q000473:pathology* / Q000503:physiopathology*; D002555:Cerebrospinal Fluid / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003244:Consciousness Disorders / Q000209:etiology; D003937:Diagnosis, Differential; D004673:Encephalomyelitis, Acute Disseminated / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D051359:Lymphohistiocytosis, Hemophagocytic / Q000134:cerebrospinal fluid / Q000150:complications / Q000473:pathology* / Q000503:physiopathology* / Q000523:psychology; D008279:Magnetic Resonance Imaging; D008297:Male; D008499:Medical Records; D008580:Meningism / Q000209:etiology; D008831:Microcephaly / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D012189:Retrospective Studies; D012640:Seizures / Q000209:etiology; D016896:Treatment Outcome