Case Reports and Comments Clippers Syndrome

Background Steroid-responsive chronic lymphocytic inflammation with ponto-cerebellar perivascular enhancement syndrome (Clippers syndrome) is a rare inflammatory disorder of the central nervous system that primarily affects the brainstem, especially the pons and adjacent regions such as the cerebellum
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Studies have shown that to characterize a case as Clippers syndrome, two main features are essential; one is the typical magnetic resonance imaging (MRI) appearance of these areas as "pepper-like" and curvilinear lesions on gadolinium enhancement, and corresponding clinical manifestations
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The second hallmark of a correct diagnosis is a marked clinical and radiographic response to glucocorticoid (GCS)-based immunosuppressants
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Therefore, the diagnosis of Clippers syndrome is based on clinical presentation, imaging findings, steroid response, and exclusion of other diagnoses by imaging, serum, and CSF laboratory tests
.

Although the underlying pathogenesis of this condition is unclear and neuropathological studies are far from clear, we have reason to believe that this manifests as a pathological feature of immune-mediated inflammatory diseases with marked vascular and perivascular tropism primarily Occurs in the pons and peripontine area
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However, 7.
0T ultra-high-field MRI showed perivascular inflammation not only in the brainstem and cerebellum, but also in normal brain regions on 3.
0T MRI
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The immunological nature of Clippers syndrome has recently been demonstrated
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The results showed that CD45+ lymphocytes, mainly CD3+ T cells and CD4+ T cells, accumulated in the brainstem, cerebellar vessel wall and surrounding blood vessels of patients with Clippers syndrome
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CD4+ T cells also infiltrated the brainstem parenchyma
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The presence of CD8+ T cells was not evident, with only a few CD20+ B cells
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An omics-based approach revealed upregulation of cell adhesion molecules (VCAM-1, ICAM-1), interleukins (IFN-γ, TNF-β, IL-1, IL-6, IL-10) and deposition of IgG Important in the pathogenesis of Clippers syndrome, but its central role is of course the activation of complement
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This makes them considered potential targets for the treatment of Clippers syndrome
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Monoclonal antibodies are very promising in this regard, and the first positive results have been published
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In this case report, we demonstrate that early identification of the syndrome and targeted diagnostic approaches allow for more effective treatment, earlier patient prognosis, and limit or avoid unnecessary complications
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The content of this article comes from the sharing of clinical cases abroad.
Compiler: Li Lin, Deputy Chief Physician of the Department of Neurology, Zhengzhou Central Hospital Affiliated to Zhengzhou University
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Case Report History and Physical Examination: A 40-year-old man was admitted to the Neurological Infectious Diseases Center with complaints of persistent dizziness, vertigo, unsteady gait, blurred vision, weakness, fatigue, and decreased work capacity for more than a month
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There is no relevant medical or family history
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General clinical examination was normal
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Clinical neurological examination revealed left-sided diplopia, left-sided facial hypoesthesia, slight left deviation of the tongue, and slight tremor in the complex bare-probe hand
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Nery, Stryumpel, Sharapov, and Chaddok were positive on one or both sides
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No meningeal sign was found
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Intentional coordination test and shaking with Romberg sign
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Related examinations: lumbar puncture was performed on admission, cerebrospinal fluid analysis showed an increase in lymphocytes of 16/L, and protein and glucose were normal.

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Serological tests for HSV1/2, CMV, EBV, VZV, mumps, adenovirus and enterovirus were all negative
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Cerebrospinal fluid PCR detection of herpes virus, Mycobacterium tuberculosis, Toxoplasma gondii DNA were all negative, and no oligoclonal band was found
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MRI showed a small lesion in the subtentorial cerebellum with inflammatory manifestations in the pons that spread to the upper and lower cerebellar peduncles without a clear outline
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The T2 image signal was significantly enhanced, the total size of the T1 weakened area was 22x47x28mm, and after gadolinium-enhanced scanning, the structure of the displayed area retained the uneven accumulation of contrast agent (Figures 1 and 2)
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Figure 1 Figure 2 Diagnosis and Treatment: The patient did not have a brainstem biopsy for a neuropathological diagnosis, but met the clinical and MRI criteria for Clippers syndrome proposed by Tobin et al.
Extensive examination did not yield an alternative diagnosis
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Oral steroid therapy was initiated with methylprednisolone at a daily i/v dose of 12 mg, tapering to 4 mg per day over a month, with multiple steroid abstinence therapy
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We observed significant improvement in clinical symptoms and partial remission of MRI lesions with methylprednisolone
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Analysis and discussion Clippers syndrome is a syndrome of chronic inflammatory pontine lesions, peripontine enhancement on MRI scans, and a good response to steroids
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The disease is extremely rare, and its etiology and pathogenesis remain unclear
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Although a full set of diagnostic criteria has not been established, MRI findings of pepper-like punctate enhancement in the center of the pons are considered a hallmark of Clippers syndrome
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However, new data show inflammatory processes involving distant regions of the brain and spinal cord, which reduce the diagnostic value of neuroimaging
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In addition, such clinical and neuroimaging findings can also occur in other pathological processes and therefore cannot be considered specific to this disease
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The diagnostic value of the second important criterion - a good response to steroids appears to be more controversial
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In fact, almost all diseases with overt inflammatory conditions respond to immunosuppressants, including steroids
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Not surprisingly, corticosteroid treatment was often associated with resolution of neurological symptoms and resolution on magnetic resonance imaging with gadolinium enhancement
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Therefore, successful steroid therapy is a key criterion for confirming the diagnosis of Clippers syndrome
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However, the clinical effects of steroids are usually temporary and rarely curative
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Disease progression is accompanied by a reduction and attenuation of remission
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In fact, some patients were initially diagnosed with Clippers syndrome due to its characteristic clinical and radiological symptoms, which later turned out to be atypical presentations of malignant lymphoma and other inflammatory and non-inflammatory diseases
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Therefore, exclusion of other possible causes of abnormality is a necessary condition for correct diagnosis
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Conclusions Clippers syndrome appears to be a mysterious and rare variant of encephalitis involving parenchymal inflammation and vasculitis, which presents a real challenge for physicians to make a definitive diagnosis
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Despite efforts to elucidate its pathogenesis, Clippers syndrome remains a controversial disease classification
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Therefore, it is necessary to make a diagnosis in any case of unknown etiology of encephalitis, especially in recurrent and elderly patients
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Early diagnosis and appropriate treatment can improve the prognosis of the disease
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However, the previously mentioned diagnoses cannot clearly differentiate Clippers syndrome due to low specificity and unclear symptoms, which requires us to search for new diagnostic tools that are highly correlated with symptoms
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Original source: dol: 10.
36740/WLek202101131.
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