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

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus

Neuroradiological images on admission and 3 weeks after steroid therapy and pathological findings from brain biopsy. Representative T1-weighted imaging with gadolinium enhancement (top row) and corresponding T2-weighted imaging (bottom row) on cervical MRI demonstrate changes of MRI features after steroid therapy. The images performed on admission show punctate and nodular enhancing lesions in the bilateral pons, the basal ganglia, the midbrain, the pontine brachium, and extensively in cerebral white matter, with a perivascular enhancement pattern (A1, A2). A decrease in the number and extent of pathology is observed on a cervical MRI scan after steroid treatment (B1, B2). In pathology findings from the parietal lobe specimen, hematoxylin and eosin staining showed lymphocytic inflammatory infiltration with perivascular and parenchymal cells (C; × 100). The lymphocytic infiltrates were mainly composed of CD3+ T lymphocytes (D; ×100). Proliferation rate, detected by Ki67 antigen immunohistochemistry, was about 10% (E; ×100). MRI = magnetic resonance imaging.
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Figure 1: Neuroradiological images on admission and 3 weeks after steroid therapy and pathological findings from brain biopsy. Representative T1-weighted imaging with gadolinium enhancement (top row) and corresponding T2-weighted imaging (bottom row) on cervical MRI demonstrate changes of MRI features after steroid therapy. The images performed on admission show punctate and nodular enhancing lesions in the bilateral pons, the basal ganglia, the midbrain, the pontine brachium, and extensively in cerebral white matter, with a perivascular enhancement pattern (A1, A2). A decrease in the number and extent of pathology is observed on a cervical MRI scan after steroid treatment (B1, B2). In pathology findings from the parietal lobe specimen, hematoxylin and eosin staining showed lymphocytic inflammatory infiltration with perivascular and parenchymal cells (C; × 100). The lymphocytic infiltrates were mainly composed of CD3+ T lymphocytes (D; ×100). Proliferation rate, detected by Ki67 antigen immunohistochemistry, was about 10% (E; ×100). MRI = magnetic resonance imaging.

Mentions: Brain magnetic resonance imaging (MRI) showed hyperintense signal on T2-weighted images, associated with patchy gadolinium enhancement on T1-weighed images in the bilateral pons, the basal ganglia, the midbrain, the pontine brachium, and diffuse white matter (Fig. 1A1, A2). The clinical and MRI findings could suggest other disorders, such as neurosarcoidosis, CNS vasculitis, autoimmune encephalitis, histiocytosis and paraneoplastic disease. These differential diagnoses can be excluded by extensive evaluations and the previously reported cases.[1] Bilateral parietal lobe brain biopsy revealed lymphocytic inflammatory infiltration in perivascular and parenchymal area (Fig. 1C), consisting primarily of CD3+ T lymphocytes (Fig. 1D) and few detected CD1a+ cells, CD30+ cells, CD10+ cells and CD20+ cells. All infiltrated cells were negative for CD56, CD99, TDT, or CD14. The proliferation rates, as detected by Ki67 antigen immunohistochemistry was ∼10% (Fig. 1E). Neuropathology lacked characteristic microglial nodules or neuronophagia. No demyelination, granulomatous inflammatory, or necrotizing vasculitis was observed.


Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) with intracranial Epstein – Barr virus infection
Neuroradiological images on admission and 3 weeks after steroid therapy and pathological findings from brain biopsy. Representative T1-weighted imaging with gadolinium enhancement (top row) and corresponding T2-weighted imaging (bottom row) on cervical MRI demonstrate changes of MRI features after steroid therapy. The images performed on admission show punctate and nodular enhancing lesions in the bilateral pons, the basal ganglia, the midbrain, the pontine brachium, and extensively in cerebral white matter, with a perivascular enhancement pattern (A1, A2). A decrease in the number and extent of pathology is observed on a cervical MRI scan after steroid treatment (B1, B2). In pathology findings from the parietal lobe specimen, hematoxylin and eosin staining showed lymphocytic inflammatory infiltration with perivascular and parenchymal cells (C; × 100). The lymphocytic infiltrates were mainly composed of CD3+ T lymphocytes (D; ×100). Proliferation rate, detected by Ki67 antigen immunohistochemistry, was about 10% (E; ×100). MRI = magnetic resonance imaging.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5120928&req=5

Figure 1: Neuroradiological images on admission and 3 weeks after steroid therapy and pathological findings from brain biopsy. Representative T1-weighted imaging with gadolinium enhancement (top row) and corresponding T2-weighted imaging (bottom row) on cervical MRI demonstrate changes of MRI features after steroid therapy. The images performed on admission show punctate and nodular enhancing lesions in the bilateral pons, the basal ganglia, the midbrain, the pontine brachium, and extensively in cerebral white matter, with a perivascular enhancement pattern (A1, A2). A decrease in the number and extent of pathology is observed on a cervical MRI scan after steroid treatment (B1, B2). In pathology findings from the parietal lobe specimen, hematoxylin and eosin staining showed lymphocytic inflammatory infiltration with perivascular and parenchymal cells (C; × 100). The lymphocytic infiltrates were mainly composed of CD3+ T lymphocytes (D; ×100). Proliferation rate, detected by Ki67 antigen immunohistochemistry, was about 10% (E; ×100). MRI = magnetic resonance imaging.
Mentions: Brain magnetic resonance imaging (MRI) showed hyperintense signal on T2-weighted images, associated with patchy gadolinium enhancement on T1-weighed images in the bilateral pons, the basal ganglia, the midbrain, the pontine brachium, and diffuse white matter (Fig. 1A1, A2). The clinical and MRI findings could suggest other disorders, such as neurosarcoidosis, CNS vasculitis, autoimmune encephalitis, histiocytosis and paraneoplastic disease. These differential diagnoses can be excluded by extensive evaluations and the previously reported cases.[1] Bilateral parietal lobe brain biopsy revealed lymphocytic inflammatory infiltration in perivascular and parenchymal area (Fig. 1C), consisting primarily of CD3+ T lymphocytes (Fig. 1D) and few detected CD1a+ cells, CD30+ cells, CD10+ cells and CD20+ cells. All infiltrated cells were negative for CD56, CD99, TDT, or CD14. The proliferation rates, as detected by Ki67 antigen immunohistochemistry was ∼10% (Fig. 1E). Neuropathology lacked characteristic microglial nodules or neuronophagia. No demyelination, granulomatous inflammatory, or necrotizing vasculitis was observed.

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus