Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) with intracranial Epstein–Barr virus infection

Abstract

Background:Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory disorder in the central nervous system (CNS) with distinct clinical, radiological, and pathological features. The pathophysiology of CLIPPERS still remains unclear and the reports are quite few. Although the radiological lesions were reported to be located predominantly in the pons, brachium pontis, and cerebellum, other adjacent structures such as the white matter and spinal cord were very recently reported as involved regions in CLIPPERS. In this study, we report a case of CLIPPERS presenting with intracranial Epstein–Barr virus (EBV) infection and diffuse white matter involvement.Case summary:A 37-year-old male was diagnosed with mediastinal Hodgkin's lymphoma (lymphocyte predominance type) at the age of 26, and then obtained complete remission after treatment and remained free of relapse for 11 years. He was admitted with 7 months’ history of mental disorder, and 20 days’ history of gait and limb ataxia, dysphagia, and cough. The diagnosis of CLIPPERS was established based on the findings of punctate and nodular enhancing lesions in the bilateral pons, the basal ganglia, the mid-brain, the pontine brachium, and diffuse white matter in magnetic resonance imaging (MRI), together with CD3+ T-lymphocytic inflammatory infiltration in perivascular and parenchymal area revealed by bilateral parietal lobe brain biopsy. Also, our patient exhibited a good response to steroid therapy and remained free of relapse for 5 months. Importantly, we found intracranial Epstein–Barr virus infection in this patient.Conclusion:CLIPPERS might be an autoimmune disorder, and intracranial EBV-infection raises the possibility that EBV-associated autoimmunity is associated with CLIPPERS pathogenesis.

Recurrent Epstein-Barr Virus-positive (EBV+) Primary Central Nervous System Lymphoma (PCNSL) in a Patient with Clinical Features of Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS)

“…This parameter usually becomes elevated during EBV reactivation (18). Interestingly, one report described a case of CLIPPERS in which EBV infection led to a dramatic elevation of the EBV DNA level in the CSF, while a PCR failed to detect EBV in the serum and no EBV involvement was detected in a brain biopsy specimen using in situ hybridization of EBER (19). Moreover, several reported cases of CLIPPERS have occurred in patients with immunosuppressive backgrounds, such as patients with history of chemotherapy or steroid use, which may be involved in EBV reactivation (16, 19, 20).…”

“…Interestingly, one report described a case of CLIPPERS in which EBV infection led to a dramatic elevation of the EBV DNA level in the CSF, while a PCR failed to detect EBV in the serum and no EBV involvement was detected in a brain biopsy specimen using in situ hybridization of EBER (19). Moreover, several reported cases of CLIPPERS have occurred in patients with immunosuppressive backgrounds, such as patients with history of chemotherapy or steroid use, which may be involved in EBV reactivation (16, 19, 20). Given the features of our case and the reported cases, EBV infection or reactivation in the CNS may be associated with the core features of CLIPPERS (i.e., punctate “peppering” enhanced lesions or perivascular T-cell infiltration), which are also observed in cases of EBV+ DLBCL or CNS-LYG.…”

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) associated with or without lymphoma: Comparison of clinical features and risk factors suggestive of underlying lymphomas

“…By September 2018, a total of 88 cases had been reported, with 10 of them associated with lymphoma [4][5][6][7][8][9][10][11][12][13]. An upward tendency of CLIPPERS followed since the first description in 2010, indicating the rising awareness of this disease entity.…”

“…As for the aggressiveness of lymphoma, 7 of the 8 patients with Non-Hodgkin's lymphoma were diagnosed as invasive lymphoma, except for the patient with mycosis fungoides-type cutaneous Tcell lymphoma. Few patients had had prior cutaneous, mediastinal or lymphonodal lesions, but all these patients had the disease in remission and no lesions at presentation when CLIPPERS associated with lymphoma was diagnosed [9,11,12].…”

“…Meanwhile, however, more and more reports about lymphoma mimicking the manifestations of CLIPPERS followed. Patients diag-nosed as CLIPPERS associated with lymphoma often had poor prognoses rather than the benign processes in CLIPPERS patients without lymphoma [4][5][6][7][8][9][10][11][12][13]. Different treatment strategies should be adapted against these two different diagnoses.…”