2026 American Academy of Neurology Abstract Website

Objective:

Hemophagocytic lymphohistiocytosis is a rare multisystem disorder characterized by proliferation and diffuse infiltration multiple organs with histiocytes, including the central nervous system. To emphasize that IIC with inflammatory cerebrospinal fluid (CSF) indices and EEG abnormalities may represent the earliest manifestation of CNS-HLH, warranting urgent immunochemotherapeutic intervention.

Background:

A previously healthy adult male was hospitalized three times within one month for recurrent pancytopenia, abdominal pain, and transient encephalopathy that resolved spontaneously. On his third admission, he developed neutropenic fever, acute kidney injury, and rapidly progressive encephalopathy with myoclonic jerks. Brain MRI was unremarkable. Continuous EEG showed generalized periodic discharges at 1.5–2 Hz with superimposed sharply contoured morphology, consistent with an ictal–interictal continuum pattern. A trial of IV lorazepam led to attenuation of discharges and transient improvement, but his EEG and clinical status continued to worsen despite antiseizure therapy. CSF demonstrated lymphocytic pleocytosis (687/µL), elevated protein (139 mg/dL), and normal glucose. Infectious, autoimmune, metabolic, and toxicologic workup was negative. In contrast, hemophagocytic markers were markedly elevated (H-score 206, high soluble IL-2 receptor, elevated CXCL9 and CRP, low haptoglobin, positive DAT). Flow cytometry revealed CD4+ T-cell expansion, consistent with secondary hemophagocytic lymphohistiocytosis (HLH) with CNS involvement. Bone marrow biopsy showed normocellular trilineage hematopoiesis with erythroid predominance and no malignancy.

Design/Methods:

none

Results:

Empiric intrathecal methotrexate and systemic dexamethasone/etoposide produced rapid clinical and electrographic improvement, confirming that CNS-HLH encephalopathy. No secondary trigger was identified. Repeat CSF analysis showed marked improvement, highlighting the critical role of early neuro-immunologic detection and intervention in CNS-HLH.

Conclusions:

CNS-HLH may present as inflammatory encephalopathy with IIC patterns. Early EEG recognition and prompt immunochemotherapy can enable rapid neurologic recovery and normalization of CSF markers, emphasizing the need to consider CNS-HLH in patients with hyperinflammatory syndromes and unexplained encephalopathy.