J Korean Neurosurg Soc.  2015 Nov;58(5):487-490. 10.3340/jkns.2015.58.5.487.

Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids with a Significant Elevation of beta-2 Microglobulin Levels

• Fujisawa N
• Oya S
• Mori H
• Matsui T

• KMID: 2191418
• DOI: http://doi.org/10.3340/jkns.2015.58.5.487

Abstract

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a relapsing-remitting disorder for which steroid administration is a key to control the progression. CLIPPERS can exhibit radiological features similar to malignant lymphoma, whose diagnosis is confounded by prior steroid administration. We report a case of CLIPPERS accompanied by abnormal elevation of beta-2 microglobulin in the cerebrospinal fluid (CSF). A 62-year-old man started to experience numbness in all fingers of his left hand one year ago, which gradually extended to his body trunk and legs on both sides. Magnetic resonance imaging demonstrated numerous small enhancing spots scattered in his brain and spinal cord. CSF levels of beta-2 microglobulin were elevated; although this often indicates central nervous system involvement in leukemia and lymphoma, the lesions were diagnosed as CLIPPERS based on the pathological findings from a biopsy specimen. We emphasize the importance of biopsy to differentiate between CLIPPERS and malignant lymphoma because the temporary radiological response to steroid might be the same in both diseases but the treatment strategies regarding the use of steroid are quite different.

Keyword

Biopsy; beta-2 microglobulin; Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids; Diagnosis; malignant lymphoma

MeSH Terms

Biopsy
Brain
Central Nervous System
Cerebrospinal Fluid
Diagnosis
Fingers
Hand
Humans
Hypesthesia
Inflammation*
Leg
Leukemia
Lymphoma
Magnetic Resonance Imaging
Middle Aged
Spinal Cord
Steroids*
Steroids

Figure

• 

  Fig. 1 A series of brain MR images demonstrating enhancing lesions. The lesions were hypointense on T1-weighted images (A) and hyperintense on T2-weighted images (B). Small enhancing spots were distributed in the pons and cerebellum (C), temporal (D), and frontal (E) lobes, and spinal cord (F). Biopsy specimen was obtained from the lesions in the right cerebellum (G, arrow).

• 

  Fig. 2 Photomicrographs of sections from the biopsy specimen. A : Small lymphocytes invaded all layers of the blood vessels in the white matter. B : The invasion of CD3-positive cells was noted. C : CD20-positive cells were dominantly distributed in the perivascular areas. D and E : CD4-positive T cells (D) were more prominent than CD8-positive T cells (E). Original magnifications are ×100 (A) and ×200 (B-E).

• 

  Fig. 3 MR images one year after the initiation of steroid therapy. Signal changes remained on T1- (A) and T2- (B) weighted images, but enhancing lesions disappeared (C).

Reference

1. Bagnato F, Zivadinov R, Cecchinelli D, Tancredi A, Grop A, Pierallini A, et al. beta2-microglobulin serum level is not a marker of disease activity in multiple sclerosis. Eur J Neurol. 2004; 11:455–460. PMID: 15257683.

2. Baraniskin A, Kuhnhenn J, Schlegel U, Chan A, Deckert M, Gold R, et al. Identification of microRNAs in the cerebrospinal fluid as marker for primary diffuse large B-cell lymphoma of the central nervous system. Blood. 2011; 117:3140–3146. PMID: 21200023.

3. Buttmann M, Metz I, Brecht I, Brück W, Warmuth-Metz M. Atypical chronic lymphocytic inflammation with pontocerebellar perivascular enhancement responsive to steroids (CLIPPERS), primary angiitis of the CNS mimicking CLIPPERS or overlap syndrome? A case report. J Neurol Sci. 2013; 324:183–186. PMID: 23149266.

4. Mavlight GM, Stuckey SE, Cabanillas FF, Keating MJ, Tourtellotte WW, Schold SC, et al. Diagnosis of leukemia or lymphoma in the central nervous system by beta 2-microglobulin determination. N Engl J Med. 1980; 303:718–722. PMID: 6157089.

5. Oksanen V, Grönhagen-Riska C, Tikanoja S, Somer H, Fyhrquist F. Cerebrospinal fluid lysozyme and beta 2-microglobulin in neurosarcoidosis. J Neurol Sci. 1986; 73:79–87. PMID: 3517236.

6. Peterslund NA, Black FT, Geil JP, Mogensen CE. Beta-2-microglobulin in the cerebrospinal fluid of patients with infections of the central nervous system. Acta Neurol Scand. 1989; 80:579–583. PMID: 2694728.

7. 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; 133:2626–2634. PMID: 20639547.

8. Roy S, Josephson SA, Fridlyand J, Karch J, Kadoch C, Karrim J, et al. Protein biomarker identification in the CSF of patients with CNS lymphoma. J Clin Oncol. 2008; 26:96–105. PMID: 18056677.

9. Scott BJ, Douglas VC, Tihan T, Rubenstein JL, Josephson SA. A systematic approach to the diagnosis of suspected central nervous system lymphoma. JAMA Neurol. 2013; 70:311–319. PMID: 23319132.

10. Simon NG, Parratt JD, Barnett MH, Buckland ME, Gupta R, Hayes MW, et al. Expanding the clinical, radiological and neuropathological phenotype of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). J Neurol Neurosurg Psychiatry. 2012; 83:15–22. PMID: 22056964.

11. 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; 69:847–855. PMID: 22777259.

12. Taieb G, Wacongne A, Renard D, Figarella-Branger D, Castelnovo G, Labauge P. A new case of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids with initial normal magnetic resonance imaging. Brain. 2011; 134(Pt 8):e182. author reply e183. PMID: 21303857.