Central nervous system (CNS) involvement is a critical prognostic factor for hemophagocytic lymphohistiocytosis

Abstract

BackgroundHemophagocytic lymphohistiocytosis (HLH) is a rare multisystem disorder that frequently involves the central nervous system (CNS). We compared the clinical characteristics, treatment, and prognosis of patients with HLH according to the degree of CNS involvement.MethodsThe clinical manifestations, initial laboratory data, treatment, and outcomes for 50 patients diagnosed with HLH and treated at Asan Medical Center between January 1995 and August 2011 were retrospectively reviewed and analyzed. CNS involvement was defined as the presence of neurological symptoms or an elevated white blood cell (WBC) count in the cerebrospinal fluid (CSF).ResultsAmong these 50 patients, 23 (46%) developed CNS disease. Among patients with CNS disease, 19 had neurological symptoms, including seizures, altered consciousness, facial palsy, dysarthria, and dysphagia. Four patients had elevated CSF WBC counts without neurological symptoms. Twelve patients had abnormal brain imaging results, including high signal intensity lesions on T2-weighted magnetic resonance imaging (MRI) findings, ventriculomegaly, hemorrhage, atrophy, and leptomeningeal enhancement. Patients with CNS disease had lower ferritin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels as well as reduced 5-year survival as compared to those without CNS disease.ConclusionCNS involvement is common among patients with HLH. Overall, patients with CNS disease achieve poorer outcomes than patients without CNS involvement. To improve outcomes, physicians must carefully monitor the neurological manifestations in patients with HLH and administer the appropriate course of intensified chemotherapy to patients with CNS disease.

Successful treatment of recurrent CNS disease post‐bone marrow transplant in children with familial hemophagocytic lymphohistiocytosis

“…HLH is a rare, but serious hyperinflammatory syndrome characterized by a pattern of abnormal clinical findings. CNS involvement occurs in 37–73% of patients and must be controlled in order for successful disease resolution . It may present at diagnosis or any time throughout the course of treatment.…”

“…Known mutations affecting the perforin/granzyme pathway of NK cell cytotoxicity include PRF1 (perforin), SNTX 11, MUNC 13–4, and MUNC 18–2. 3 Central nervous system (CNS) involvement ranges from 37 to 73% of patients at diagnosis or during the course of HLH and is associated with higher mortality rates . CNS disease manifests by neurological symptoms, abnormal cerebrospinal fluid (CSF), abnormal neuroradiological imaging, or a combination of these.…”

“…3 Central nervous system (CNS) involvement ranges from 37 to 73% of patients at diagnosis or during the course of HLH and is associated with higher mortality rates. [4][5][6][7][8] CNS disease manifests by neurological symptoms, abnormal cerebrospinal fluid (CSF), abnormal neuroradiological imaging, or a combination of these. Abnormal CSF at diagnosis is associated with higher rates of mortality and more severe neurological outcomes Pediatr Blood Cancer 2016;63: 2154-2158 c 2016 Wiley Periodicals, Inc. 2154 wileyonlinelibrary.com/journal/pbc (18-21%) in surviving patients.…”

Neuroimaging Findings in Pediatric Genetic Skeletal Disorders: A Review

“…In the majority of cases, GSDs are multisystem diseases with multiple associated complications in the gastrointestinal, endocrine, cardiopulmonary, or central nervous systems (CNSs). In the evaluation of GSDs, CNS abnormalities play a key role in determining an overall prognosis . In GSDs, CNS abnormalities may be caused by the same underlying genetic defect (primary abnormalities) or the skeletal dysplasia itself (secondary abnormalities).…”

Between a rock and a hard place

“…The history of lymphoma, age of the patient, rare atypical cells in the bone marrow biopsy and hypermetabolic enlarged spleen on PET-CT were highly suggestive of either a de novo or relapsed splenic lymphoma, however a definitive tissue diagnosis, which is required for initiation and selection of the chemotherapy regimen was lacking. The progression of the neurologic symptoms has been reported to portend a poor prognosis [14], and prompted the initiation of systemic and intrathecal therapy for HLH. CNS involvement by HLH is common ( 50%) and the manifestations are varied, so that any neurologic, radiologic or CSF abnormalities are considered evidence of involvement until proven otherwise.…”