Pontine Perivascular Enhancement Research Articles

A Rare Neurological Presentation of Familial Hemophagocytic Lymphohistiocytosis

AbstractIn this case report, we described a 15-year-old boy who presented with intermittent episodes of ataxia and diplopia since 6.5 years of age. Extensive workup done over several years was negative. Brain biopsy showed a neuroinflammatory disorder, and hence, differential diagnosis of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, central nervous system (CNS) lymphoma, and small vessel CNS vasculitis were considered. A final diagnosis of familial hemophagocytic lymphohistiocytosis was made when the patient developed episodes of prolonged fever with pancytopenia much later in the course of illness and genetic workup revealed pathogenic mutations in the PRF1 gene.

Chronic Lymphocytic inflammation with Pontine perivascular enhancement responsive to steroids (CLIPPERS): A unique pathology and stroke mimic (1100)

Chronic Lymphocytic inflammation with Pontine perivascular enhancement responsive to steroids (CLIPPERS): A unique pathology and stroke mimic (1100)

Clippers the Brain Biter: An Adolescent’s Experience

Introduction: Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids is a rare inflammatory Central Nervous System disorder prominently affecting the brainstem. We present an adolescent’s reflection on this condition complicated with Epstein-Barr virus induced CNS Lymphoma. Case report: A 16-year-old boy presented about 5 years ago with a balance problem. He was diagnosed by MRI after ongoing debate whether this is juvenile multiple sclerosis. He initially responded to methylprednisolone but developed acute deterioration requiring 8 cycles of Infliximab and Methylprednisolone. He then confirmed cerebellar lymphoma 2 years later hence commenced on chemotherapy and radiotherapy after posterior fossa decompression. He gradually losses his motor skills, left hemiparesis and spasticity. He needs tracheostomy and gastrostomy due to poor bulbar function. Now, he is fully dependent and requires chest physiotherapy and suctioning and cystostomy for urinary incontinence. He has multiple PICU admissions due to recurrent aspiration, acute cerebellar oedema and post posterior fossa decompression. He worries about family breakdown as mum is his sole carer and having regular nightmare. He changed school to meet his care demands and unsure how to adapt to new environment. Social experience makes him anxious due to lack of understanding about his condition. He is evidently having low self-esteem and confidence. Discussion: Children palliative care team has been involved since diagnosis to support him and family. He is understandably depressed and clinical psychologist input bear minimal impact. He is fully aware of the current situation and his wish to rap Eminem’s songs like he used to do it before. Conclusion: Early aggressive treatment in CLIPPERS aim to prevent neuroaxonal loss. However, due to bellicose nature of the condition, the prognosis is relatively poor. Managing adolescent expectation after gradual deterioration is challenging especially, he is aware that achieving ‘normality’ is impossible as the treatment advancement still in limbo.

CLIPPERS. Three clinical cases and review

CLIPPERS (Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) is a rare inflammatory disease of the central nervous system, during which the pons of the brain is damaged. This disease was described for the first time in 2010 by S.J. Pittock et.al. At present, there have been around 50 described cases of the disease. Up to the present moment, there are difficulties diagnosing this disease. In the article, a literature review and three clinical cases are presented. Furthermore, the necessity of further research is shown for improving the accuracy and specificity of the diagnostic criteria, as well as for defining biomarkers and developing algorithms of effective therapy.

En mann i 60-årene med gangvansker, dysartri og lett kognitiv svikt

BACKGROUND Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) syndrome is an immune-mediated, treatable and inflammatory CNS disease first reported by Pittock et al. (2010). CASE PRESENTATION We describe a 66-year-old man with previous history of diabetes, atrial fibrillation and hypertension, who was admitted to hospital with reduced general condition. He had experienced dizziness and unstable gait for a year, and had been periodically confused, especially in the previous month. MR imaging showed characteristic punctuate and curvilinear gadolinium enhancements in the pons. Our patient was diagnosed with CLIPPERS and was given corticosteroid treatment, initially methylprednisolone intravenously and then prednisone orally. Other differential diagnoses, such as CNS lymphoma, high-grade glioma, CNS vasculitis, neurosarcoidosis, demyelinating disease, Bickerstaff brainstem encephalitis, and acute disseminated encephalomyelitis were ruled out. The patient's condition improved dramatically after corticosteroid treatment. INTERPRETATION In 2017, the diagnostic criteria for CLIPPERS were published. Based on these criteria we were able to diagnose this patient with possible CLIPPERS, consistent with clinical symptoms, MRI findings, absence of better explanations for the condition, and clinical and radiological improvement after treatment with corticosteroids. An unequivocal diagnosis of CLIPPERS can only be established by characteristic pathological findings.

Atypical Pediatric Demyelinating Diseases of the Central Nervous System

Pediatric central nervous system demyelinating diseases include multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and acute disseminated encephalomyelitis (ADEM). As diagnostic criteria become more inclusive, the risk of misdiagnosis of atypical demyelinating diseases of rheumatologic, infectious, and autoimmune etiology increases. We review mimics of multiple sclerosis, neuromyelitis optica spectrum disorder, and acute disseminated encephalomyelitis, including rheumatologic diseases: systemic lupus erythematosus and neuro-Behçet disease; infectious diseases: human immunodeficiency virus, progressive multifocal leukoencephalopathy, and subacute sclerosis panencephalitis; and autoimmune diseases including X-linked Charcot-Marie-Tooth disease, chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) and autoimmune glial fibrillary acidic protein (GFAP) encephalopathy. Atypical demyelinating disease may mimic classic neuroinflammatory diseases of the central nervous system. Imaging may meet criteria for a diagnosis of multiple sclerosis, or patients may present with optic neuritis and transverse myelitis consistent with neuromyelitis optica spectrum or myelin oligodendrocyte glycoprotein (MOG) antibody disorders. Through careful history-taking and review of atypical MRI findings, we may avoid misdiagnosis and mistreatment.

Peripheral T cell lymphoma after chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): a case report

BackgroundChronic 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 characteristics. The pathophysiology of CLIPPERS still remains unclear. Because a few cases about lymphoma mimicking the manifestations of CLIPPERS were reported and the prognosis of lymphoma is much worse, early identification of lymphoma is very important.Case presentationA 31-year-old woman was admitted with 3 months’ history of diplopia, dizziness, gait ataxia, and right facial numbness. The diagnosis of CLIPPERS was established based on the finding of punctate enhancing lesions in the cerebellum, thalamus, pons, medulla, and midbrain region in magnetic resonance imaging (MRI), together with the favorable clinical and radiological responses to corticosteroids. However, she was diagnosed as peripheral T cell lymphoma, not otherwise specified (PTCL-NOS) by the pulmonary nodular and the skin biopsy almost 10 years later, and she got complete remission within 1 year after chemotherapy.ConclusionWe report the first case of CLIPPERS developing PTCL-NOS. This case proposes that when brain biopsy was difficult to achieve, biopsies in extra-cerebral lesions under the assisting examination of positron emission tomography-computed tomography (PET-CT) can be helpful in further identification.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) – a case report

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) – a case report

A case of clippers with spinal cord presentation

Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids is an inflammatory condition primarily involving the pons and adjacent structures and presents with cerebellar and brainstem signs such as dysarthria, ataxia, cranial nerve palsies and long tract signs. It has characteristic MRI findings and clinico-radiologic responsiveness to steroids. It is a diagnosis of exclusion. 53 years male patient presented with 1-month history of subacute progressive paraparesis with sensory level at T10, with urinary urgency and constipation. However, there were no signs or symptoms referable to the brainstem. MRI revealed characteristic gadolinium enhancing punctate lesions without any mass effect in brainstem and cerebellum as well as the cervicothoracic cord and cerebral white matter. Autoimmune, malignancy and infection workup were negative. CSF analysis revealed 30 cells/cu.mm,92% lymphocytes along with protein 90 mg%.PET-CT of whole body revealed hypometabolism in the brainstem and cerebellum. Patient was started on intravenous Methylprednisolone 1 g/day for 5 days followed by Prednisolone 60 mg per day and Methotrexate. He showed significant improvement and follow up MRI scan at 2 months revealed clearing of all lesions. Typically, CLIPPERS patients present with symptoms and signs referable to the brainstem and cerebellum, however here we present a case with a predominant spinal cord presentation. Our patient was extensively worked up for alternate causes and showed typical clinical and radiologic responsiveness to steroids.

A case of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) syndrome: clinical-radiological correlation and potential role of diffusion tensor imaging

A case of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) syndrome: clinical-radiological correlation and potential role of diffusion tensor imaging

The spectrum of immune-mediated and inflammatory lesions of the brainstem: Clues to diagnosis.

The presentation of a patient with brainstem symptoms and signs invokes a number of common and less common differential diagnoses, and accurate diagnosis can be challenging. We review the major immune-mediated and inflammatory syndromes that can affect the brainstem including multiple sclerosis, neuromyelitis optica spectrum disorder, neuro-Behçet disease, chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, neurosarcoidosis, Susac syndrome, and the histiocytic disorders. We focus on clinical features and MRI clues that help to distinguish among the different brainstem conditions. Accurate diagnosis is important to guide appropriate treatment and limit neurologic disability.

Olivary hypertrophy improved by steroid treatment: Two case reports with unique presentations

Olivary hypertrophy (OH) is the secondary degeneration of the inferior olivary nucleus (ION). It is observed one month after the onset of a primary lesion within the dento-rubro-olivary pathway and is usually associated with oculopalatal tremors. Here, we report two unique cases with rare autoimmune diseases leading to OH development with progressive cerebellar ataxia, both of which improved with steroid treatment. The first patient was a 59-year-old man with slowly progressive dysarthria and ataxic gait without palatal tremor. Anti-N-methyl-d-aspartate (NMDA) receptor antibody was positive in the CSF, supporting a diagnosis of anti-NMDA receptor encephalitis. The second patient was a 56-year-old man who developed dysarthria, ataxia, gait disturbance, and palatal tremor. He was diagnosed with chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS), based on presence of a punctate contrast-enhancing lesion in the middle cerebellar peduncle, pons, and cerebellum on magnetic resonance imaging (MRI). Brain MRI in both patients demonstrated high signal intensity regions in the bilateral IONs. Semi-quantitative volume analysis of MRI revealed significant reduction in ION volume after steroid treatment and accordingly cerebellar ataxia was improved in both cases. Clinical and radiological features of the two cases were unique, indicating potential novel etiologies in the pathophysiology of OH associated with cerebellar ataxia.

Clinical spectrum of central nervous system myelin oligodendrocyte glycoprotein autoimmunity in adults.

The clinical interest for auto-antibodies against myelin oligodendrocyte glycoprotein (MOG) has recently reemerged, with the use of more specific detection methods. Large national cohorts have allowed characterizing a more precise clinical spectrum delineated by the presence of human MOG-antibodies. In adults with MOG-antibodies, optic neuritis is the most frequent clinical presentation, with features different from multiple sclerosis (MS), including bilateral involvement and predilection for the anterior part of the optic nerve. Myelitis and brainstem syndrome are also frequent, and may clinically mimic neuromyelitis optica spectrum disorders (NMOSD). Despite the frequently severe clinical presentation, most of patients recover quickly after steroids initiation. Other less typical presentations include encephalitis with seizures, cranial nerve involvement, and chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids-like. Although the majority of adult patients follow a relapsing course, long-term prognosis differs from aquaporin-4-antibodies NMOSD, with only a small proportion of patients with a poor outcome. MOG-antibodies-associated disease is a new entity in the spectrum of inflammatory demyelinating diseases, distinct from both MS and NMOSD. There is a crucial need to identify factors associated to the risk of relapse or poor outcome, to seek patient subgroups in which immunoactive treatments could be beneficial.

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

BackgroundWe 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. MethodsCLIPPERS 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. ResultsTen 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). ConclusionsHyperreflexia, 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.

CLIPPERS and its mimics: evaluation of new criteria for the diagnosis of CLIPPERS

ObjectiveTo evaluate the accuracy of the recently proposed diagnostic criteria for chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS).MethodsWe enrolled 42 patients with hindbrain punctate and/or linear...

Diffuse white matter alteration in CLIPPERS: Advanced MRI findings from two cases

Advanced MRI findings in two patients with probable chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) are presented. Diffusion tensor imaging indices (fractional anisotropy and mean diffusivity), evaluated in both patients at baseline MRI examination before treatment and during follow-up, indicated white matter structural changes not only affecting the brainstem, which represents the primary site of inflammatory damage, but also projection (corona radiata) and associative tracts in both patients, while alterations within the corpus callosum were detected in patient 1# at follow-up. Susceptibility weighted imaging (SWI) revealed hypointense lesions in both patients, MRI spectroscopy (MRS) indicated a mildly increased Cho/NAA ratio with no evidence of lipids/lactate peaks, indicating that it may be used as a non-invasive marker to identify CLIPPERS cases suspected for progression to lymphoma.

Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement not Responsive to Steroids – Management Decisions in a Situation of Diagnostic Uncertainty (P2.2-047)

Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement not Responsive to Steroids – Management Decisions in a Situation of Diagnostic Uncertainty (P2.2-047)

Progressive Parkinsonism and Cognitive Changes: A Rare Presentation of Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS) (P1.7-007)

Progressive Parkinsonism and Cognitive Changes: A Rare Presentation of Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS) (P1.7-007)

Is there a role for B cells in chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids? A case report

AbstractBackgroundChronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently defined inflammatory disorder of the central nervous system, prominently involving the brainstem. This condition is diagnosed based on clinical presentation, imaging findings and robust response to steroids, along with histopathology.Case presentationHere, we describe a case of a 47‐year‐old woman who presented with gait ataxia, bilateral leg weakness and urinary retention. Initial imaging studies were unremarkable, but on follow up she was found to have multiple enhancing lesions in the left cerebellar peduncle associated with a clinical relapse. Several weeks later, and after being treated with ocrelizumab, a B‐cell targeted therapy, she developed new neurological symptoms and was found to have new lesions on brain imaging. She was diagnosed with probable CLIPPERS. She was started on azathioprine and remained asymptomatic with normal brain imaging for several months.ConclusionsDespite adequate depletion of circulating B cells, the patient continued to have relapses associated with CLIPPERS. This supports the notion that targeted peripheral B‐cell therapy does not stop the progression of CLIPPERS.

A Case of Rare Inflammatory Brainstem Syndrome: Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids.

A Case of Rare Inflammatory Brainstem Syndrome: Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids.