Chronic hepatitis B infection presenting with chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): a case report

Abstract

IntroductionChronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids is a brainstem disorder characterized by perivascular pathologic reaction with lymphocyte infiltration and leading to diplopia, facial palsy, dysarthria, and gait ataxia. It was thought to be an autoimmune disorder without distinct pathogenesis. Chronic hepatitis B virus infection has been proposed in correlation with autoimmune diseases, including central nervous system demyelinating disease. Patients with chronic hepatitis B infection may develop the syndrome of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids.Case presentationA 34-year-old Taiwanese man who had been a hepatitis B virus carrier for a decade presented to our emergency room. He had influenza symptoms and progressive symptoms of left hemifacial numbness, double vision, and an unsteady gait of 2 days’ duration. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids was diagnosed, with increased hepatitis B viral load at the same time. He had no past history of similar neurologic deficits, and his liver function tests had been within normal limits before this episode. After corticosteroid and entecavir treatments, his neurological deficits and neuroimaging anomalies improved and his serum hepatitis B virus DNA viral load normalized.ConclusionsHepatitis B virus infection may induce central nervous system autoimmune reactions, including chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids. In such cases, concomitant administration of corticosteroids and antiviral agent was helpful. We suggest further investigations in patients with regulatory T cell dysfunction, which may assist in clarifying a loss of immune tolerance in patients with such disorders.

CLIPPERS, chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids: A challenge in neurological practice, clinical landmarks (Review)

“…This factor may also contribute to long-term neurological morbidity. Although the exact pathophysiological mechanisms of the disease are unclear, there appear to be clinical overlaps with other predominant autoimmune encephalitis of the brainstem (35,36). Neurologists should be aware of the typical conditions and manifestations, as prompt and appropriate treatment may limit the permanent neurological effects.…”

“…The pathogenesis of CLIPPERS has not yet been elucidated. The slightly elevated levels of CSF proteins without significant pleocytosis, the increased contrast in MRI lesions, a good response to steroids, and the T cell infiltrates observed in pathological studies suggest that it is an immune-mediated disease (35,36). Although there is no specific biomarker, careful exclusion of other conditions is needed to diagnose CLIPPERS.…”

Unusual CLIPPERS presentation and role of MRI examination in the proper diagnostic assessment: A case report

“…CLIPPERS was initially considered an immune-mediated CNS disorder, associated to specific trigger events responsible for transient or permanent immunologic derangement, including vaccination, HBV infection, or long-term natalizumab treatment [3,5,14]. Nevertheless, the search for possible causative events of CLIPPERS is often difficult and inconclusive.…”

The pathogenesis hypothesis and research progress of CLIPPERS: A literature review

“…At the same time, abnormal expression of Tregs will lead to autoimmune diseases. The first case of CLIPPERS connected to persistent hepatitis B virus (HBV) infection was reported by Weng et al [9] Since the prevalence of circulating CD4 + CD25 + Tregs in peripheral blood was significantly correlated with high serum HBV-DNA viral load, viral clearance function was compromised as Treg numbers rose. [10] Thus, it is proposed that immunological and regulatory T cell (Treg) dysfunction brought on by HBV may contribute to the pathology of CLIPPERS.…”

“…[47] It can also help prevent spinal cord injury. [48] Because of the viral infection hypothesis and the close relationship between nervous system diseases and high viral load, Weng et al [9] suggested that anti-HBV drugs should be added to treat CLIPPERS and closely monitor the activity of the HBV. Hou et al [40] reported a case of CLIPPERS whose symptoms were successfully relieved by hydroxychloroquine for 4 years.…”