CLIPPERS With Chronic Small Vessel Damage: More Overlap With Small Vessel Vasculitis?

Kleinschmidt‐DeMasters, Bette K.; West, Matthew

doi:10.1097/nen.0000000000000050

Cited by 19 publications

(8 citation statements)

References 28 publications

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“…Several clinical features and one neuroimaging element should be taken into consideration to generate a correct diagnosis: signs and symptoms related to the brainstem, commonly ataxia, dysarthria, and diplopia; an amelioration using steroid treatment and degradation with subsequent of withdrawal of treatment; MRI showing punctate similar to 'salt and pepper', predominantly located in the pons; and contrast enhancement (13,(20)(21)(22)(23).…”

Section: Cases From the Literaturementioning

confidence: 99%

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

et al. 2021

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Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a relatively newly discovered and characterized condition affecting the central nervous system (CNS) that involves the brainstem almost ubiquitously and that focuses primarily on the pons. Characteristically, CLIPPERS represents a combination of clinical symptoms related to the pathology of the brainstem in particular and has a characteristic appearance on magnetic resonance imaging (MRI), with punctate and curvilinear gadolinium enhancement 'peppering' the pons. The lesions can be viewed via neuroimaging with a predominance in the pons and adjacent rhombencephalic structures, such as the cerebellar peduncles, cerebellum, medulla, and middle brain. These lesions may also spread and appear in other areas of the brain such as the thalamus or white matter. As the name suggests, this clinical syndrome responds to immunosuppressive treatment based on glucocorticosteroids (GCSs), expressed as both clinical and radiological improvements. Support for this treatment is required for a long period, since exacerbations may occur without. Thus, the diagnosis of CLIPPERS has garnered increased attention from clinicians and the active exclusion of differential alternative diagnoses is needed. A specific biomarker of serum or cerebrospinal fluid (CSF) for this condition has not been discovered. The pathophysiology of this condition is not fully elucidated, and it is not yet clear whether CLIPPERS is a disease in its own right or is the culmination of several already known syndromes. Clinicians and radiologists should pay close attention to this condition as it is relatively easy to treat and patients can benefit from the early introduction of GCSs, which can produce significant results through long-term immunosuppression. Taking into account previous reports in the literature, which currently include over 50 cases reported as CLIPPERS, this analysis addressed the clinical features, and paraclinical and differential diagnoses of cases described in the literature.

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Section: Cases From the Literaturementioning

confidence: 99%

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

et al. 2021

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“…Taken together, these results show that inflammatory diseases could include particular types of neurological diseases, such as infectious diseases, multiple sclerosis and experimental allergic encephalomyelitis (EAE), but not AD or PD. Chronic lymphocytic inflammation with pontocerebellar perivascular enhancement responsive to steroid (CLIPPERS) may be categorized as an inflammatory disease, although it remains ultimately unclear whether CLIPPERS represents a separate and independent new disease entity or a syndrome with heterogeneous etiologies …”

Section: Microglial Activation and Inflammationmentioning

confidence: 99%

“…Chronic lymphocytic inflammation with pontocerebellar perivascular enhancement responsive to steroid (CLIP-PERS) may be categorized as an inflammatory disease, although it remains ultimately unclear whether CLIPPERS represents a separate and independent new disease entity or a syndrome with heterogeneous etiologies. 49,50…”

Section: Microglial Activation and Inflammationmentioning

confidence: 99%

Microglia and brain macrophages: An update

Sasaki

2016

Neuropathology

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Current immunohistochemical techniques have made the identification of microglia possible in routinely processed tissue sections from human brains. Previous studies have indicated that almost no neurological diseases exist without microglial activation. Activated microglia often secrete inflammatory cytokines in various diseases, including Alzheimer's disease, but microglial activation is not always associated with inflammation. The equation microglial activation means “neuroinflammation” is absurd and misleading. Neuropathologists are in the best position to provide clarity to end the existing confusion. The functions of microglia in the non‐diseased brain probably include a role in synaptic maintenance, but defects in the expression of specific molecules on microglia can also cause leukoencephalopathy, such as Nasu‐Hakola disease (NHD) and hereditary leukoencephalopathy with spheroids (HDLS). “Microgliopathies” is a new term used to designate conditions where microglial dysfunction is primary and at the center of the disease process. The molecules responsible are DAP12 or TREM2 in NHD and CSF1R in HDLS, respectively, but further studies are needed to clarify how exactly these microglial molecules influence the pathogenesis of axonal and myelin loss. Diffusely infiltrating glial tumors showing microglial differentiation (true microglioma) are exceedingly rare but recent evidence suggests that they indeed exist, although their molecular genetic characterization is still lacking. Participation of the expert neuropathology community will be required to identify additional cases and provide the latter. A large number of tumor‐associated macrophages (TAMs), which are partly derived from microglia, have been observed in glioblastomas. In TAMs, the expression of M2‐like molecules is higher than that of M1‐like molecules, but the number and differentiation state of TAMs vary in the intratumoral area and with the type of macrophage markers used. In future studies, we should focus on the morphological and molecular alterations of the microglia that are specific to the disease where they are observed.

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“…Other aetiological possibilities include a pre-malignant state whereby lymphocytic infiltration precedes primary CNS B-cell lymphoma as described in a few case reports originally diagnosed as CLIPPERS [12]- [16]. Additionally, a vascular aetiology has been proposed due to reports of both small [17] and large [18] vessel abnormalities and infarction [19], but vascular changes have not consistently been reported in the literature. Whilst the aetiology of CLIPPERS remains uncertain, advances in immunopathology and radiology have allowed CLIPPERS to be recognised as a distinct entity that differs considerably in its clinical presentation, immunological characteristics, radiological findings and its responsiveness to steroids.…”

Section: Discussionmentioning

confidence: 99%

CLIPPERS: A case report with radiology, three serial biopsies and a literature review

Turnquist¹,

Pretorius²,

DeLuca³

et al. 2020

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Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS) is a rare central nervous system inflammatory disorder primarily affecting the brainstem and cerebellum. We report a case of CLIPPERS in a 45-year-old man presenting with left facial numbness and dizziness. Imaging studies were conducted repeatedly over an 8-year follow up period. Given diagnostic uncertainty in the early stages of the disease, three serial biopsies were obtained, which together with the clinical and radiological findings led to the diagnosis. This case highlights the diagnostic challenges regarding the rare entity of CLIPPERS and discusses the main differential diagnoses that are necessary to consider. Additionally, some of the atypical features of this case, including the presenting finding of a large, solidly enhancing lesion on radiological imaging and prominent plasma cells on pathology, contribute expanding the spectrum of appearances for CLIPPERS.

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CLIPPERS With Chronic Small Vessel Damage: More Overlap With Small Vessel Vasculitis?

Cited by 19 publications

References 28 publications

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

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

Microglia and brain macrophages: An update

CLIPPERS: A case report with radiology, three serial biopsies and a literature review

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