To describe a novel case of multifocal brain lesions and multiple cranial neuropathies associated with lymphocyte variant hypereosinophilic syndrome (L-HES).

Hypereosinophilic syndromes (HES) are characterized by persistent eosinophilia causing end-organ damage in the absence of other explanations. L-HES results from an aberrant clonal T-cell population that over-produces cytokines that promote eosinophilia (particularly interleukin-5), leading to a variety of systemic manifestations, most commonly cutaneous, with neurologic manifestations rarely reported (primarily stroke and aseptic meningitis). 

A 57-year-old female with L-HES on oral prednisone initially presented with focal neurologic symptoms consistent with left cranial nerve V and VII neuropathies and was treated with a prednisone taper and valacyclovir. Eight months later, she developed left optic neuritis and was found to have multiple intracranial T2 FLAIR hyperintense lesions on MRI, some associated with microhemorrhages. Cerebrospinal fluid (CSF) testing revealed a lymphocytic pleocytosis, with normal protein and negative oligoclonal bands. She was treated with pulse dose steroids with partial improvement in symptoms and started on mepolizumab the following month.  Nine months after her presentation with optic neuritis, she presented with cognitive difficulties, headaches, gait disturbance, and recurrent optic neuritis. MRI revealed new T2 hyperintense lesions, some with incomplete ring enhancement, a new microhemorrhage, and left optic nerve enhancement. CSF flow cytometry revealed the same T-cell clonal population in the serum attributed to her L-HES. She was treated with IV methylprednisolone followed by a prolonged prednisone taper, with 1 month interval MRI demonstrating near resolution of lesions.  Peginterferon alfa-2a was added to her regimen with sustained improvement at five month follow up.

This case presents rarely documented neurological manifestations of L-HES. Peginterferon alfa-2a, an activator of JAK-STAT signaling, may also prove useful in medically refractory cases with neurologic disease via its antiproliferative effects.