Challenging implications of CLIPPERS syndrome with atypical presentation: report of two cases

Background: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an increasingly recognized neuroinflammatory syndrome that predominantly affects pontine and cerebellar brain structures. Characteristically, patients develop glucocorticoid-responsive brainstem disorders, demonstrate pontocerebellar contrast-enhancement (CE) on magnetic resonance imaging (MRI) and exhibit an angiocentric, lymphocytic infiltrate in brain biopsies. In this report, the authors present and discuss two novel and challenging cases of CLIPPERS to highlight the clinical and radiological diversity of the syndrome.

Case description: The first case describes a 66-year-old male patient with dizziness, headaches, gait disturbances, mild cognitive impairment and visual field loss to the left side. MRI revealed 1 cerebellar and 2 occipital CE lesions, suspicious for intracerebral metastases. The second case describes a 53-year-old male patient with temporal lobe epilepsy, anomic aphasia and mild cognitive impairment. MRI examination demonstrated 4 CE lesions in the pons, the temporal lobe and the thalamus, suspicious for intracerebral lymphoma. Due to the radiological presentation, neoplastic diseases were the most plausible differential diagnoses in both patients. However, repeated biopsies ruled out tumor manifestation but were finally consistent with CLIPPERS. Significant and long-lasting response to immunosuppressive treatment approved this diagnosis.

Conclusions: In both case reports, CLIPPERS imitated malignant tumor growth. This scenario can challenge clinicians and necessitates an implementation of this neuroinflammatory syndrome as a differential diagnosis in neuro-oncology.

Keywords: CLIPPERS; biopsy; case series; pons; steroids.