Central nervous system involvement of hypereosinophilic syndrome: a report of 10 cases and a literature review

Background: The central nervous system (CNS) may be affected in those cases of peripheral eosinophila without a secondary cause (hypereosinophilic syndrome, HES). The pathomechanism of CNS involvement in HES remained uncertain.

Methods: We included those with CNS symptoms and peripheral eosinophilia (>1500/μl) at the time of presentation. Those with identifiable causes of eosinophilia were excluded. In addition to data analysis of our cases, we reviewed the literature using the Medline database.

Results: Ten patients were recruited. Half of them presented with altered mental status. None of the patients had significant risk factors such as endomyocardial disease (EMD). Their brain magnetic resonance imaging (MRI) showed multiple ischemic lesions in the border zone (BZ) and other cortical areas. In addition to our 10 cases we included 67 cases from a literature review. The total 77 cases were systemically analyzed. We found that the most common type of CNS involvement was cerebrovascular disease (CVD, 63.6%), multifocal lesions in BZ were the most common feature on MRI (45.5%), many patients presented with altered mental status (40.3%), and direct eosinophil infiltration into brain parenchyma was rare in pathologic studies and not found in the patients with CVD. Furthermore, although EMD was one of the major cardiac abnormalities (26.0%), cardiac workup more frequently showed non-EMD or normal findings. Cardiac abnormalities, altered mental status, and higher eosinophil counts were more common in those with poor outcomes, whereas an isolated CNS manifestation was more frequent in those with favorable outcomes. Finally, the presence of altered mental status was the most significant predictor of poor clinical outcomes, whereas isolated CNS involvement and corticosteroid treatment were significant predictors for favorable outcomes.

Conclusions: Multiple lesions on MRI were suggestive of an embolic mechanism, but diagnostic workup failed to find significant risk factors such as EMD in the most cases. Impaired anticoagulation by eosinophilic cationic proteins could be an alternative mechanism. Direct invasion of eosinophils into the CNS was rare and those cases with isolated CNS manifestations showed a better prognosis. The preferential indirect involvement of CNS by eosinophils ("CNS-tropism") may underlie the neurological manifestations of HES. Early administration of corticosteroid after ruling out secondary causes can be beneficial in HES with CNS manifestation.