Efficacy of Intravenous Immunoglobulins against Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids: A Case Report.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory disease of the central nervous system that predominantly affects the brainstem. Apart from corticosteroids, there are few reported treatment options for CLIPPERS, and there is no standard therapy. A 77-year-old man presented with diplopia that had persisted for 5 months. Dysarthria and numbness of the distal right upper extremity and right lips were also observed. Brain magnetic resonance imaging (MRI) revealed a hyperintense area around the brainstem. Symptoms were relieved immediately following intravenous methylprednisolone (IVMP) administration. However, after gradual tapering of oral prednisolone to 5 mg/day, the symptoms relapsed, and brain imaging revealed that the condition had worsened. Intravenous immunoglobulins (IVIg) were administered for recurrence, with no clinical improvement. After each IVMP treatment, the patient recovered promptly. Based on the patient's symptoms and characteristic MRI findings, exclusion of other diseases, and the significant efficacy of corticosteroids, he was diagnosed with CLIPPERS. There was no recurrence at a maintenance prednisolone dose of 8 mg/day. IVIg had a poor effect on the acute phase of CLIPPERS symptoms. Compared with other immunosuppressants, IVIg is less effective in suppressing the relapse of CLIPPERS.

Brain MRI Findings of Hemophagocytic Lymphohistiocytosis With a Heterozygous PRF1 Gene Mutation Masquerading As CLIPPERS: A Case Report.

Familial hemophagocytic lymphohistiocytosis is a rare and potentially life-threatening genetic condition characterized by unsuppressed immune activation and hypercytokinemia. Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS) is a central nervous system inflammatory disorder characterized by punctate and curvilinear gadolinium-enhancing lesions in the brainstem, cerebellum, and spinal cord, which responds well to corticosteroid treatment. Hemophagocytic lymphohistiocytosis has been known to mimic CLIPPERS on neuroimaging, and patients previously diagnosed with CLIPPERS may carry familial hemophagocytic lymphohistiocytosis-related gene mutations that serve as predisposing factors. In this article, we describe a case initially diagnosed with CLIPPERS based on characteristic magnetic resonance imaging features and clinical course, who was later diagnosed with hemophagocytic lymphohistiocytosis based on a heterozygous familial hemophagocytic lymphohistiocytosis-associated PRF1 gene mutation.

MOG antibody associated disease (MOGAD) presenting with extensive brain stem encephalitis: A case report.

Background: Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is a relatively new entity of demyelinating diseases, clinically presenting with optic neuritis, transverse myelitis, or encephalic symptoms. Typical radiological features include demyelinating cerebral and spinal lesions, cortical involvement, leptomeningeal enhancement, or tumefactive lesions. Here we present a rare case of a young patient with extensive brain stem lesion on the MRI while exhibiting nystagmus, singultus and somnolence. Case presentation: A 30-year-old male patient presented initially with fever and impaired consciousness, but furthermore developed nystagmus, singultus and tetraparesis during the following week. Repeated MRI examinations revealed extensive brain stem edema with notable bilateral affection of the cerebellar peduncles and the pons. Antiviral and antibiotic treatment was changed to intravenous corticosteroids and immunoglobulins as soon as the diagnosis of MOGAD was established by testing serum and cerebrospinal fluid positive for MOG specific antibodies. MRI alterations vanished completely over time with a delayed, nearly complete clinical recovery of our patient. Conclusion: Brain stem affection in MOGAD is rare. However, in patients presenting with an unclear brain stem encephalitis the possibility of MOGAD should be considered and tested using MOG antibodies. In case of a positive testing treatment with steroids and immunoglobulins seems recommendable.

Clinical characteristics, management, and outcomes of CLIPPERS: A comprehensive systematic review of 140 patients from 100 studies.

INTRODUCTION: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare inflammatory disorder of the central nervous system, characterized by symptoms referable to the brainstem and cerebellum such as, diplopia, gait ataxia and cerebellar dysarthria. The features and outcomes of CLIPPERS remains uncertain. we conducted this comprehensive systematic review to summarize all the existing studies that described CLIPPERS in the literature and to provide a quantitative assessment on the clinical characteristics, management, and outcomes of this rare syndrome. METHODS: A comprehensive search of PubMed and Web of Science databases was conducted from inception until January 15, 2022, was conducted. We only included the cases that clearly reported probable or definite diagnosis of CLIPPERS based on Taieb et al.'s criteria. The quality of the included studies was assessed using the JBI Critical Appraisal Tool. Descriptive statistics were performed to analyze the studies. Data were expressed as mean and standard deviation (SD) for continuous variables and proportions for categorical variables. RESULTS: We identified 100 case reports and series including a total of 140 patients with CLIPPERS (mean age: 46±18 years and males were 60%). The average follow-up duration was 32.27±57.8 months. Ataxia was the most common presenting symptom. Sixteen percent of the cases were associated with malignancy, mostly hematologic malignancies. The overall relapse rate was 59.2%, and the duration of steroid therapy was considerably shorter in the relapsed cases than in the non-relapsed (mean 6.19±7.9 vs. 10.14±12.1 days, respectively, P = 0.04). The overall mortality rate was 10%, but mortality in patients with malignancy was 30% and it was 12% in patients with relapses. In the case of steroid dosing (less than 20 mg/d versus greater than 20 mg/d) there was no significant modification in the risk of relapse. CONCLUSION: CLIPPERS is a rare clinical syndrome that affects mainly middle-aged males. Diagnosis of CLIPPERS is often challenging, and delays in diagnosis and treatment can lead to unfavorable outcomes. Therefore, neurologists should maintain a high index of suspicion for CLIPPERS in any patient presenting with symptoms and signs referrable to the brainstem. These patients should be screened for associated malignancies, especially hematological malignancies. The cases associated with malignancy tend to have worse outcomes. The relapse rate is relatively high. The relapse rate may be associated with worse mortality. Based on our findings, we recommend that CLIPPERS be treated with high-dose steroid therapy for at least ten days during the acute phase with a very slow taper. Prospective studies with a larger sample size are needed to validate our findings and guide the clinical care of these patients.

Punctate Enhancement of Bilateral Basal Ganglia in a Case of Epstein-Barr Virus Encephalitis.

Epstein-Barr virus (EBV) encephalitis is caused by initial infection or reactivation of EBV. In adults, the risk factors of EBV encephalitis include human immunodeficiency virus infection, immunosuppressant drugs, congenital immune deficiencies, post-stem cell transplantation, and post-solid organ transplantation. However, a few cases of adult-onset EBV encephalitis without these risk factors were also reported. The efficacy of steroid or intravenous immunoglobulin remains unclear in the treatment of EBV encephalitis. Herein, we report a case of an 82-year-old man with fever and disturbance of consciousness who was diagnosed as having EBV encephalitis. Gadolinium-enhanced magnetic resonance imaging showed punctate enhancement in the bilateral basal ganglia, which resembled chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). Symptoms and enhanced lesions improved after immunotherapy. Immunotherapy may be effective in the treatment of EBV encephalitis with CLIPPERS-like lesions.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, a mimicker of malignancy: a case report and review of the literature.

BACKGROUND: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids is a clinically and radiographically distinct inflammatory syndrome affecting multiple structures of the brain, including the cerebellum, brainstem, and spinal cord. The clinical presentation can be variable, including ataxia, nystagmus, dysarthria, dysphagia, and other subacute brainstem, cranial nerve, or cerebellar symptoms. These symptoms can be subacute to chronic, episodic, and progressive, making the diagnosis challenging. The hallmark radiographic magnetic resonance imaging findings are gadolinium-enhancing punctate lesions predominantly "peppering" the pons in a perivascular pattern. CASE PRESENTATION: Here, we describe a case and literature review of a 74-year-old Caucasian male who presented with subacute symptoms of ataxia, diplopia, and generalized fatigue. Physical examination was notable for horizontal nystagmus and wide-based gait. Magnetic resonance imaging revealed angiocentric enhancement predominantly in the brainstem and cerebellum, with involvement of the basal ganglia, thalami, and supratentorial white matter. Meanwhile, a screening computed tomography scan demonstrated a right upper lobe mass with biopsy proving primary lung cancer. Biopsy of one of the brain lesions showed perivascular infiltrate primarily composed of CD3+ T cells, scattered CD20+ B cells, and no signs of malignancy. The patient was started on high-dose glucocorticoids followed by a maintenance regimen with rapid improvement clinically and radiographically. Given extensive work-up was negative, these clinical and radiographic findings were consistent with chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids. CONCLUSIONS: This case illustrates the difficulty of diagnosing chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, given its variable presentation, lack of specific laboratory findings, and poorly understood pathogenesis. We demonstrate a case that responded well to oral corticosteroid burst followed by a taper to the lowest corticosteroid dose clinically possible. Failure to recognize this syndrome could result in permanent central nervous system morbidity. Therefore, earlier recognition is crucial for this treatable condition.

Increased Number of Perivascular CD20-Positive B Lymphocytes in the Neuropathology of CLIPPERS: Findings of 6 Patients from Mainland China.

INTRODUCTION: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) syndrome is a recently described chronic inflammatory disease of the central nervous system. There are few reports of CLIPPERS in the Chinese population to date. We summarized the clinical characteristics of 6 CLIPPERS patients to deepen the understanding of this disease. METHODS: The clinical manifestations and treatment of 6 CLIPPERS patients confirmed by pathology or clinical diagnosis in our hospital were retrospectively analyzed. RESULTS: The common clinical manifestations included ataxia, dysarthria, diplopia, dysphagia, dizziness, cognitive impairment, facial paresthesia, and paralysis. Most of the lesions showed typical symmetric "pepper powder"-like dot and nodular enhancement centered in the pontine and cerebellum except 1 patient with unilateral nodular enhancement. The brain histopathological examination of the 5 biopsied patients indicated that, with the exception of patient 4 with no lymphocyte infiltration, a large amount of perivascular lymphocytic infiltration was found in the other 4 patients, among whom only 1 patient was dominated by CD3+ T cell infiltration and the other 3 patients were dominated by CD20+ B cell infiltration. After treatment with intravenous methylprednisolone, all patients had significant clinical recovery associated with complete or significant MRI recovery, but they were prone to relapse after withdrawal or reduction of the corticosteroid. CONCLUSION: Our reports highlight the importance of neuropathological examinations when encountering atypical imaging manifestations, such as unilateral and large nodular Gd+ lesions, in order to establish a final diagnosis of CLIPPERS. In addition, the lymphocytic infiltration in the lesions of CLIPPERS may be dominated by CD20+ B cells instead of CD3+ T cells.

The external carotid artery as a rare feeder of a spinal dural arteriovenous fistula causing cervical myelopathy: A review of the literature.

Introduction: A causal relationship between SDAVF's and cervical myelopathy is exceedingly rare. 1-2% of these lesions are located at the craniocervical junction of which 12% are caused by arterial feeders from the external carotid artery. A correct diagnosis can be challenging with a high rate of initial misdiagnosis. Research question: Which aspects constitute the most important potential pitfalls in the diagnostic workup and treatment of SDAVF's with feeders from the external carotid artery causing cervical myelopathy? Material and methods: We performed a PRISMA-guided review of the literature in which fourteen articles were included. We illustrate the diagnostic hazards through one of our own cases. Results: SDAVF's at the cervical segment contain unique clinical and radiographic characteristics which differ from those elsewhere. Cervical myelopathy is caused by a SDAVF in 2.3% of cases. Pitfalls are numerous and diagnosis can be challenging, due to a broad differential diagnosis, potential isolated lower extremity involvement and absence of spinal cord edema on MRI. MR-alterations not always correlate with fistula localization. Discussion and conclusion: A SDAVF should be part of the differential diagnosis in patients with subacute tetraparesis. When MRI shows signal alterations in combination with enlarged perimedullary vessels, a SDAVF should be suspected. Spinal angiography should include the vertebrobasilar system, as well as the internal and external carotid arteries. Early and adequate occlusion by means of an endovascular or neurosurgical approach of the draining radicular veins should be pursued. A multidisciplinary approach is key in the diagnostic workup and treatment of these patients.

Asymptomatic brainstem lesions and pachymeningeal enhancement after anti-PD-1 therapy.

Neurological immune-related adverse events (irAEs) are rare toxicities that occur following immune checkpoint inhibitor therapy. We propose that patients with thymic malignancies and graft-versus-host disease (GVHD) are predisposed to irAEs. We present two asymptomatic patients, one with thymoma and another with GVHD, who developed abnormal brain MRIs after treatment with programmed cell death protein 1 inhibitors. The first patient, with thymic cancer and thymoma, developed pontine enhancing MRI lesions following treatment with pembrolizumab. The second patient, with prior GVHD, developed pachymeningeal enhancement following treatment with nivolumab. IrAEs with abnormal MRI studies, despite asymptomatology, have significant impact on the treatment strategy for these patients.

A Case Report of Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy Diagnosed After Long Term Diagnosis of Chronic Lymphocytic Inflammation With Pontine Perivascular Enhancement Responsive to Steroids.

Cases of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy who were initially diagnosed with chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) were rarely reported. Herein, we reported a 31-year-old woman who presented with 7 years of recurrent headache. Her clinical history, symptoms, brain MRI enhancement features, and response to treatment during each attack were reviewed. Her brain MRI 7 years ago demonstrated characteristic pepper-like enhancement of pontine and cerebellum and her symptoms resolved completely after taking a high-dose of steroids. She was suspected with the diagnosis of CLIPPERS, and she experienced five relapses once the oral steroid was tapered below 20 mg/day. During her last relapse, she experienced fever and psychosis, and GFAPα-antibodies were detected in her serum and cerebrospinal fluid by antigen-transfected HEK293 cell-based assay (indirect immunofluorescence assay). She obtained relief again after steroid therapy, and her diagnosis converted to autoimmune GFAP astrocytopathy. Autoimmune GFAP astrocytopathy may mimic CLIPPERS, both clinically and radiologically. Long-term follow-up is essential for necessary diagnosis revision at each new attack in patients with a diagnosis of CLIPPERS.

Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS): A Rare Treatable Neuroradiological Spectrum.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare CNS inflammatory disorder involving the pons and other parts of the brainstem. It is characterised by a combination of brainstem symptoms and classical magnetic resonance imaging (MRI) features of bilateral, symmetrical punctate, perivascular enhancement of pontine lesions. Another hallmark feature of this rare disease is the responsiveness to corticosteroid treatment. As the corticosteroid treatment is tapered, the symptoms exacerbate and worsen the clinical outcome. Clinicians and radiologists should be aware of this infrequent inflammatory disorder and should always be considered as a differential diagnosis. Herein, we report the case of a 17-year-old female with a similar clinicoradiological spectrum as CLIPPERS.

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

Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids syndrome (CLIPPERS) is a newly described, underestimated CNS inflammatory disorder involving predominantly the midbrain and the cerebellum. CLIPPERS pathogenesis is largely unknown, and its clinical manifestations are polymorphic and sometimes confounding. Recently clinical, radiological and pathological diagnostic criteria have been proposed to discriminate CLIPPERS from potential mimickers, but the diagnosis still remains challenging. Here we present the case of a patient with radiological findings consistent with CLIPPERS but with atypical clinical presentation, highlighting the importance of a proper diagnostic assessment.

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.

BACKGROUND: We studied patients with chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) associated with or without lymphoma and measured risk factors suggestive of an underlying lymphoma and follow-up outcomes. METHODS: CLIPPERS patients associated with or without lymphoma were included into this study. Clinical presentations were documented, risk factors suggestive of an underlying lymphoma were tested, and prognostic differences in terms of death were compared. RESULTS: Ten patients had a diagnosis of CLIPPERS associated with lymphoma, with 6 B-cell non-Hodgkin lymphoma, 2 T-cell non-Hodgkin lymphoma and 2 Hodgkin lymphoma. Using multivariate logistic analysis, the following 3 independent risk factors were found to be related to a final diagnosis of lymphoma: hyperreflexia (HR 16.56; 95% CI 1.03-265.29; p = 0.032), elevated protein in CSF (HR 11.59; 95% CI 1.24-108.39; p = 0.047), and recurrences between 2 months and 1 year after treatment (HR 29.27; 95% CI 2.09-409.58; p = 0.012). The model calibration was satisfactory (p = 0.392 with the Hosmer-Lemeshow test), and the discrimination power was good (area under the receiver operating characteristic curve 0.921; p < 0.001, 95% CI 0.826-1.000). Patients with CLIPPERS associated with lymphoma had higher mortality rate and lymphoma was a significant predictor of total mortality (HR 0.040; 95% CI 0.006-0.262; p = 0.001). CONCLUSIONS: Hyperreflexia, elevated protein in CSF and recurrences between 2 months and 1 year after treatment are risk factors suggesting an underlying lymphoma. Relapses during high-dose steroids maintenance therapy can be indicative of lymphoma, too. Patients having CLIPPERS associated with lymphoma have a worse prognosis than those without lymphoma.

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).

Primary central nervous system lymphoma (PCNSL) and chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) can share clinical features and may be indistinguishable, even after brain biopsy. We encountered a case of Epstein-Barr virus-positive (EBV+) PCNSL recurrence in a patient with clinical features of CLIPPERS, and repeat brain biopsy was required to reach the correct diagnosis. Four years after the initial diagnosis and treatment of PCNSL, "peppering" punctate enhanced lesions with transient steroid responsiveness were detected during brain magnetic resonance imaging (MRI). A second brain biopsy supported a diagnosis of CLIPPERS, while a third biopsy confirmed the diagnosis of recurrent PCNSL.

Idiopathic Central Nervous System Inflammatory Disease in the Setting of HLA-B27 Uveitis.

Purpose: The purpose of the article is to describe a novel case of idiopathic central nervous system inflammatory disease with bilateral human leukocyte antigen (HLA)-B27-positive anterior uveitis. Methods/Results: A 15-year-old African American boy with bilateral HLA-B27-positive anterior uveitis controlled with topical and oral steroids for 8 months acutely developed headaches, left eyelid ptosis, and binocular diplopia. Imaging showed lesions in the right midbrain, superior colliculus, cerebellar peduncles, and cerebellar vermis and leptomeningeal enhancement along the vermian foliae. Cerebral spinal fluid tests showed mild lymphohistiocytic pleocytosis with negative cytology; inflammatory and infectious workup were negative. He received intravenous methylprednisolone without initial symptomatic improvement; repeat magnetic resonance imaging (MRI) showed reduced lesion burden. Oral steroids were continued; his symptoms resolved in 1 month. Repeat MRI 2 months after presentation showed almost complete lesion resolution. Conclusions: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) was diagnosed. HLA-B27 positivity may represent a novel association with CLIPPERS.

Isolated painful trigeminal neuropathy as an unusual presentation of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids: A case report.

BACKGROUND: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory central nervous system disorder, typically presenting with subacute symptoms referable to brainstem and cerebellar pathology. This is the first report of CLIPPERS presenting with a painful trigeminal neuropathy. CASE REPORT: We report an unusual case of CLIPPERS presenting with facial pain and sensory symptoms, in the absence of other brainstem or cerebellar signs. Perivascular enhancement of peri-pontine structures on neuroimaging, lymphocytic infiltrate on histopathology and rapid clinical and radiological responsiveness to glucocorticosteroids were key to diagnosis. Extensive investigations excluded various differential aetiologies. CONCLUSION: The pathogenesis of CLIPPERS is poorly understood, and the diagnostic criteria are yet to be validated. In this case, facial pain was not associated with other brainstem or cerebellar signs, broadening current understanding of how CLIPPERS may present. This has clinical implications in guiding future investigations for patients presenting with painful trigeminal neuropathy.

Comparison of costs and outcomes of patients presenting with a rare brainstem syndrome.

In this case report we compare two patients presenting with similar symptoms of a brainstem syndrome including ataxia, dysarthria, and diplopia. Their MRIs showed hyperintense FLAIR signal changes with patchy areas of contrast enhancement within the brainstem particularly the pons and cerebellum. The broad differential diagnosis of this brainstem pathology included rhomboencephalitis, neurosarcoidosis, lymphoma, vasculitis, infection, and paraneoplastic or autoimmune process. Patient 1 had an extensive work up including CSF cytology, MRI brain spectroscopy, full body CT, cerebral angiogram, and ultimately brainstem biopsy. None of these studies were diagnostic of a specific etiology and total cost was $176,069. After months of declining medical condition without a clear diagnosis, chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) was considered and the patient began steroid therapy resulting in clinical and radiographic improvement. Patient 2 had serum and CSF studies that were negative for infectious, paraneoplastic, and other inflammatory processes. The team diagnosed CLIPPERS and initiated steroid therapy within days resulting in dramatic clinical and radiographic resolution. The workup cost $12,905. Comparison of these cases shows how early awareness of CLIPPERS and a directed diagnostic work up can limit invasive diagnostic testing, expedite initiation of effective therapy, improve patient outcomes, and reduce cost.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): A lymphocytic reactive response of the central nervous system? A case report.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroid (CLIPPERS) was first described in 2010. The characteristic clinical picture, radiological distribution and steroid response have been well-described in previous reports. However, the underlying pathogenesis and nosological position of CLIPPERS in the CNS require further investigation for the primary CNS lymphoma have been identified by autopsy subsequently. Here, we report a 51-year-old woman who was diagnosed with CLIPPERS but progressed to primary CNS lymphomatoid granulomatosis, which supports that CLIPPERS is not just an inflammatory CNS disorder.

CLIPPERS and the need for long-term immunosuppression.

Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS) is a rare chronic inflammatory disorder of the central nervous system. Herein, we describe the case of a 62-year-old female who presented with right sided facial tingling, gait ataxia and diplopia. Neuroimaging revealed pontine curvilinear enhancing lesions with extension into cerebellar peduncles, characteristic of CLIPPERS. This report discusses the differential diagnosis and the importance of prolonged immunomodulatory treatment for this rare neuro-inflammatory disorder. Long-term immunosuppression appears to be mandatory in order to achieve sustained remission and prevent disability related to atrophy of the structures involved in repeated attacks.

Clinical and pathological analysis of recurrent chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids：one case report / 中华神经科杂志

Objective To report a case presented with atypical clinical and radiological appearance in the early stage and finally pathologically confirmed as chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids ( CLIPPERS) , aiming to improve the understanding of the disorder. Methods The clinical, imaging, laboratory and pathological features as well as treatment and prognosis of a pathologically confirmed CLIPPERS patient with repeated relapsing-remitting course and stepwise progression in nine years were retrospectively analyzed. Results There were five relapsing-remitting processes in total clinical course of nine years. The clinical and radiological appearance was atypical in the early stage. At the first attack, the patient presented with fever, headache, altered consciousness and epileptic seizure. In the following courses, the patient presented with ataxia, blurred vision and limb weakness. Brain MRI (2006-2009) showed multiple abnormal signals including supratentorial white matter, pons and cerebellum with patchy gadolinium enhancement. Treatment with steroids resulted in a favorable clinical and radiological improvement. The symptoms of this attack included limb weakness, blurred vision, dysdipsia and dysarthria. Physical examination showed cognitive dysfunction, multiple cranial nerves injuries and bilateral pyramidal signs. Brain MRI showed multiple abnormal signals involved pons and cerebellum predominantly as well as supratentorial white matter with punctate gadolinium enhancement peppering the pons and cerebellum. A characteristic predominantly T lymphocytic perivascular infiltration was seen on brain biopsy. Both the imaging and histological findings were consistent with the CLIPPERS features. High-dose steroids treatment was given and obvious clinical and radiological improvements were observed. After discharge, steroids were reduced slowly combined with the use of immunosuppressant to avoid relapse of the disorder. Conclusions There is heterogeneity in clinical manifestations of CLIPPERS with repeated relapsing-remitting course and imaging presentations are sometimes atypical in the early stage, which leads to the misdiagonsis and missed diagnosis. Distinctive pathology is the “gold standard” for definite diagnosis. The nosological position of CLIPPERS is still unclear. Repeated relapse-remitting leads to secondary cerebral atrophy and degeneration, with the risk of progressing to primary central nervous system lymphoma. Early and vigorous steroids treatment with continuing maintenance immunotherapy results in the decreased relapse and best long-term prognosis. The neurologist should strengthen the understanding of CLIPPERS for early correct diagnosis and treatment aiming to reduce the functional disability.