Chronic Lymphocytic Inflammation Research Articles

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) – a case report and a review of the latest scientific reports

The paper presents a case of a 61-year-old patient with chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS), along with a detailed description of the diagnostic and therapeutic process, as well as radiological records reflecting the evolution of lesions depending on the steroid therapy used. We also refer to the latest literature reports on the aetiology, pathogenesis, diagnosis and treatment of this clinical entity, including its potential relationship with lymphoproliferative and lymphohistiocytic processes. Furthermore, we present a spectrum of diseases that can clinically and radiologically mimic CLIPPERS (CLIPPERS-mimics), along with the proposed differential diagnosis. Finally, the paper presents the recommended treatment strategy for both acute disease and a maintenance therapy, with particular emphasis on the role of steroid therapy.

CLIPPERS

We present the clinical case of a woman suffering from CLIPPERS syndrome (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids). The images obtained from the brain magnetic resonance...

What is chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids?

What is chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids?

Area postrema involvement in chronic lymphocytic inflammation with pontine perivascular enhancement

Area postrema involvement in chronic lymphocytic inflammation with pontine perivascular enhancement

NEUROPSYCHOLOGICAL CHARACTERISTIC OF COGNITIVE DISORDERS IN PATIENT WITH CLIPPERS SYNDROME

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a novel inflammatory central nervous system disorder. The diagnosis is made on the basis of the radiological, neurological, neuropathological data and responsiveness to steroids treatment. The aim of this paper is to present a neuropsychological characteristic of cognitive, executive and linguistic symptoms characteristic for patient with CLIPPERS disease. In this paper we present the case of a 42-year-old woman with hyperintense punctate foci in the pons, cerebellum, midbrain, thalamus, white matter of occipital lobes, with a short-term verbal memory deficits, mild deficiency in verbal and procedural learning, executive dysfunctions, hand-eye coordination impairment, psychomotor speed disabilities and dysarthria, associated with a chronic lymphocytic inflammation. In this challenging diagnosis of CLIPPERS, neuropsychological analysis of cognitive functions can be important to optimize the diagnosis and treatment.

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.

Palpebral Pleomorphic Adenomas of the Lacrimal Gland.

To report the characteristics and management for patients with palpebral pleomorphic adenoma of the lacrimal gland. The records for patients with palpebral pleomorphic adenoma seen at Moorfields Eye Hospital between 1978 and 2019 were reviewed for demographics, presentation, imaging, histopathology, management, and outcome. Forty-three patients (25 male; 58%) with palpebral pleomorphic adenoma were identified, presenting at a mean age of 46 years (median 46.4 years; range 24-81 years) with symptoms for an average of 31 months (median 18.0 months; range 1 month to 17 years). The commonest symptom was a painless upper lid lump (37 patients; 86%), although 4 patients (9%) had a localized ache, and 1 (2%) had episodic epiphora. A moderately-mobile, firm round mass (like a "chick-pea") was readily palpable in 39/43 (91%) patients, and significant ptosis and upper lid swelling was noted in 6 cases (14%). Imaging was reviewed in 35 patients, 28 (80%) having a well-defined homogeneous mass in front of the orbital rim, on the anterior pole of the lacrimal gland. With the exception of 8 tumors removed from the actual palpebral lobe using a conjunctival incision, all others were excised intact through an upper eyelid skin-crease incision. Histopathology confirmed an intact pseudocapsule in 39/43 (91%) and 10 (23%) had a mild chronic lymphocytic inflammation within the tumor and/or neighboring lacrimal gland. There were no tumor recurrences at an average follow-up of 40 months (median 9.1; range 2 weeks to 230 years). Most palpebral pleomorphic adenomas are discovered as an upper lid lump and a few first become manifest as upper lid swelling with ptosis. To avoid inadvertent incisional biopsy, they should be recognized preoperatively-especially as most are readily palpable as a hard lump superotemporally, often freely mobile in the suborbicularis plane (anterior to the tarsus and main lacrimal gland). Excision, generally easiest through a transcutaneous route, was judged intact in all cases and confirmed in 91% of histological reports, with no recurrent tumors.

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.

Nasal and Lacrimal Sac Histopathology in Patients With Granulomatous Polyangiitis Undergoing Lacrimal Drainage Surgery.

To examine histological changes within nasal and lacrimal sac mucosa harvested from patients with granulomatous polyangiitis (GPA) who required lacrimal drainage surgery. As these patients were considered quiescent on clinical and serological grounds, particular attention was paid to the presence of active vasculitis. Retrospective noncomparative case series. Patients with GPA who had open lacrimal drainage surgery under the care of a single surgeon between 1991 and 2017. All patients had paired biopsies of both nasal and ipsilateral lacrimal sac mucosa. Biopsies of the nasal and lacrimal sac mucosa, taken from the operative site during either primary or revisional open dacryocystorhinostomy, were reported by experienced ophthalmic histopathologists. Outcome measures were the surgical appearance of the tissues and the proportion of each tissue showing histological evidence of active vasculitis, chronic inflammation with or without fibrosis, marked fibrosis without inflammation, or acute-on-chronic inflammatory changes. Paired tissues were available from 47 patients (25 females; 53%) who had undergone 64 procedures (57 primary, 7 revisional). All patients had systemic disease, this being known prior to surgery in 43 patients (with 41/43 on long-established systemic immunosuppression) and suspected clinically after the initial lacrimal examination in 4/47. Most lacrimal sacs and nasal spaces showed a variety of abnormalities, this commonly being extensive scarring. Despite most patients being considered to have inactive systemic GPA, active vasculitis was evident in 23/64 (36%) lacrimal sac biopsies and 32/64 (50%) nasal mucosal biopsies-suggesting that serological markers may not be reliable guide to disease activity where disease is of limited volume (as, for example, with limited sino-nasal disease). Chronic lymphocytic inflammation was present in a further 35/64 (55%) sacs-associated with marked fibrosis in 5-and a further 25/64 (41%) nasal biopsies (with fibrosis in 2). The lacrimal sac and nasal space are highly abnormal in most patients with GPA undergoing lacrimal drainage surgery. Despite having clinically and serologically inactive disease on established systemic immunotherapy, histological examination often shows unrecognized active vasculitis, which might indicate inadequate systemic immunosuppression for the underlying condition.Lacrimal sac and nasal mucosa from patients with granulomatous polyangiitis undergoing dacryocystorhinostomy usually show chronic lymphocytic inflammation with marked fibrosis, but up to half reveal active vasculitis despite long-established systemic immunosuppression and apparently "quiescent" disease.

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.