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Table of Contents    
LETTER TO EDITOR
Year : 2018  |  Volume : 66  |  Issue : 4  |  Page : 1160-1162

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids and human leukocyte antigen


1 Department of Neurology, Osaka Red Cross Hospital, Osaka, Japan
2 Department of Neurology, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan

Date of Web Publication18-Jul-2018

Correspondence Address:
Dr. Rie Tohge
Department of Neurology, Osaka Red Cross Hospital, Osaka
Japan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.237020

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How to cite this article:
Tohge R, Nagao M. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids and human leukocyte antigen. Neurol India 2018;66:1160-2

How to cite this URL:
Tohge R, Nagao M. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids and human leukocyte antigen. Neurol India [serial online] 2018 [cited 2018 Nov 18];66:1160-2. Available from: http://www.neurologyindia.com/text.asp?2018/66/4/1160/237020




Sir,

A 62-year old man developed low-grade fever and anorexia 5 months prior to admission. He presented with progressive intellectual decline and delirium lasting for 3 months. He also complained of ataxic intentional tremors. On neurological examination, his Mini–Mental State Examination score was 17/30. Saccadic eye movements were observed. Deep tendon reflexes were brisk in all four limbs. Bilateral ankle clonus and pathological reflexes were positive. Vibratory and proprioceptive deficits in both legs, spastic and wide-based gait, and mild neck stiffness were observed. Tandem gait was impossible to carry out.

Brain magnetic resonance imaging (MRI) revealed punctate gadolinium enhancement of the pons [Figure 1]a and [Figure 1]b. Fluid-attenuated inversion recovery (FLAIR) images demonstrated high-intensity lesions and swelling of bilateral uncus and amygdala [Figure 1]c and [Figure 1]d. Cervical and thoracic spinal cord T2-weighted MRI revealed high-intensity lesions extending continuously from the medulla to the conus [Figure 2]a, with scattered punctate gadolinium enhancement within this region [Figure 2]b. Laboratory investigations revealed elevated serum immunoglobulin (Ig) E (201 IU/mL [normal: <170 IU/mL]) and antithyroglobulin antibody (191 IU/mL [normal: <27 IU/mL]) levels. Ultrasonography revealed diffuse thyroid enlargement, although the patient was euthyroid. The patient was seronegative for anti-NH2-terminal of alpha-enolase and other antineuronal antibodies including anti-Hu, anti-Ri, anti-Yo, anti-Tr, anti-myelin-associated glycoprotein, anti-myelin, anti-Ma/Ta, anti-glutamic acid decarboxylase, anti-amphiphysin, anti-aquaporin 4, anti-glutamate receptor, anti-GABA-b receptor, anti-LGI1, anti-CASPR2, and anti-glycine receptor antibodies. Antibodies associated with collagen disorders and tumor markers were also absent. He was seronegative for herpes simplex virus, human herpes virus-6, varicella-zoster virus, Epstein–Barr virus, and cytomegalovirus IgM. Serum lactic acid, pyruvic acid, vitamin B12, and angiotensin-converting enzyme levels were within normal range. Soluble interleukin-2 receptor level was mildly elevated (729 IU/mL). Cerebrospinal fluid (CSF) analysis revealed pleocytosis (101 white blood cells/mm 3, 100% lymphocytes) and elevated total protein (151 mg/mL). IgE level was undetectable. Oligoclonal bands were absent. Cytological analysis revealed no malignant cells. Truncal computed tomography was unremarkable. Human leukocyte antigen (HLA) typing was A2, A26, B62, and B54.
Figure 1: (a and b) Brain magnetic resonance imaging (MRI) revealed punctate gadolinium enhancement of the pons. (c and d) Fluid-attenuated inversion recovery (FLAIR) images demonstrated high-intensity lesions and swelling of bilateral uncus and amygdala

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Figure 2: (a) Cervical and thoracic spinal cord T2-weighted MRI revealed high-intensity lesions extending continuously from the medulla to the conus; and, (b) scattered punctate gadolinium enhancement is seen within this region

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His symptoms improved by the administration of intravenous methylprednisolone (1,000 mg daily for the first 3 days), followed by oral prednisolone (PSL, 1 mg/kg daily). High-intensity lesions were absent on follow-up FLAIR images acquired 12 months later, with no brain or spinal cord atrophy. After 48 months of follow-up, treatment with oral PSL was stopped. No recurrence occurred.

Pittock et al., in 2010, advocated clinical, radiological, and pathological features of a treatable condition characterized by punctate and curvilinear enhancement peppering the pons and nonspecific perivascular infiltration of T lymphocytes. The condition is now referred to as chronic lymphocytic inflammation, with pontine perivascular enhancement responsive to steroids (CLIPPERS).[1] The characteristic features in CLIPPERS are as follows: (1) It occurs in middle-aged adults; (2) it has a subacute or chronic disease course; (3) ataxia and diplopia are the initial and predominant symptoms; (4) punctate and curvilinear gadolinium-enhanced lesions are seen on imaging; (5) the CSF abnormalities include pleocytosis, elevated total protein, detection of oligoclonal bands, and a high CD4/CD8 ratio; (6) autoantibodies are present in some cases; (7) CD4-positive perivascular lymphocytic infiltration is seen on biopsy; and, (8) there is evidence of clinical and radiological response to corticosteroids.[1],[2] Compared with the radiological presentation in previously reported cases with CLIPPERS, in our patient, the punctuate-enhanced lesions of the pons were relatively mild, and the spinal cord lesions revealed typical findings of the disease. High-intensity lesions in the limbic system on T2-weighted images were also detected. Although a diagnosis of CLIPPERS requires exclusion of other diseases that share similar lesions, such as neuromyelitis optica, neurosarcoidosis, neuro-Behçet's disease, limbic encephalitis (LE) by virus infection, LE with autoimmune diseases, autoantibody-mediated LE, and malignant lymphoma, these disorders were excluded on examination. The lesions resolved with steroid therapy. The patient was cured as evidenced by the gradual tapering of his steroid dose over 4 years.

Furthermore, three Japanese cases of CLIPPERS, including our case, showed HLA typing.[3],[4] All were positive for HLA-B62. Although it is not known if the occurrence rate of HLA-B62 in the patients with CLIPPERS is significantly higher than that in the standard population, HLA typing is needed to confirm HLA-associated T-lymphocytopathy and to fully characterize CLIPPERS as a distinct disease entity.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Pittock SJ, Debruyne J, Krecke KN, Giannini C, van den Ameele J, De Herdt V, et al. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). Brain 2010;133:2626-34.  Back to cited text no. 1
    
2.
Taieb G, Duflos C, Renard D, Audoin B, Kaphan E, Pelletier J, et al. Long-term outcomes of CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) in a consecutive series of 12 patients. Arch Neurol 2012;69:847-55.  Back to cited text no. 2
    
3.
Tohge R, Nagao M, Yagishita A, Matsubara S. A case of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) in East Asia. Intern Med 2012;51:1115-9.  Back to cited text no. 3
    
4.
Kawabe M, Maekawa R, Tsuchiya K, Hideyama T, Shiio Y. A case suspected of CLIPPERS syndrome with cerebral white matter lesions. Nihon Naika Gakkai Zasshi 2015;104:2193-200.  Back to cited text no. 4
    


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