Background: Primary hemophagocytic lymphohistiocytosis (HLH) is an autosomal recessive disorder with very high mortality rates, mainly affecting infants and young children, which is characterized by fever, hepatosplenomegaly, and cytopenias. Of great clinical importance are the neurologic symptoms, which are common and may even dominate the clinical picture and precede the systemic presentation. These symptoms are extremely variable, ranging from irritability, bulging fontanelle, and neck stiffness, to convulsions, cranial nerve palsies, ataxia, hemiplegia/tetraplegia, and unconsciousness.
Methods: To elucidate this neurologic involvement further, we reviewed the neuropathologic postmortem findings from 23 children and their neurologic symptoms.
Results: Macroscopically, edema was present in many cases, and in some with advanced disease, softening and destruction of the tissue were conspicuous. The microscopic picture was exceedingly variable, ranging from almost normal to very advanced changes. In the mildest form of HLH, only the meninges were involved with infiltration of lymphocytes and macrophages (stage I), whereas more advanced cases in addition also showed perivascular infiltrates (stage II). In even more advanced disease there was also a diffuse infiltration in the tissue (stage III), as well as a multifocal necrosis. A prominent astrogliosis was present in such cases. Hemophagocytosis was seen in most patients, most commonly in the leptomeninges.
Conclusions: HLH affecting the central nervous system imitates several neurologic disorders and may be misdiagnosed. A staging system for the neuropathologic findings is presented. In children with obscure central nervous systems symptoms and a progressive encephalopathy, the diagnosis of HLH may be considered, in particular because treatments are available.