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Objectives: 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.

Conclusion: 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.

GLOSSARY: ADEM: acute disseminated encephalomyelitis

CHS: Chediak-Higashi syndrome

CRF: case report form

FHLH: familial hemophagocytic lymphohistiocytosis

FLAIR: fluid-attenuated inversion recovery

GS: Griscelli syndrome

HLH: hemophagocytic lymphohistiocytosis

HPS: Hermansky-Pudlak syndrome

HSCT: hematopoietic stem cell transplantation

MTX: methotrexate

PID: primary immunodeficiencies

SE: spin-echo

WI: weighted image

XLP: X-linked lymphoproliferative syndrome

(C)2012 American Academy of Neurology