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Show Journal of Neuro- Ophthalmology 17( 4): 243- 246, 1997. © 1997 Lippincott- Raven Publishers, Philadelphia Central Nervous System Malignant B- Cell Lymphoma Identified with Standardized Echography of the Optic Nerve Ali A. Kashani, M. D., and Barry M. Kerman, M. D. Ocular- central nervous system malignant B- cell lymphoma initially caused diplopia and morning headaches in a 10- year- old boy. After initial diagnosis of pseudotumor cerebri was made, based on normal findings from magnetic resonance imaging and magnetic resonance angiography elsewhere, he was treated with acetazolamide. Standardized echography demonstrated a combination of solid infiltration and fluid within the optic nerve sheaths. Lumbar puncture showed elevated opening pressure and cerebrospinal diagnostic of central nervous system ( CNS) B- cell lymphoma, which was confirmed by gene rearrangement. Results of peripheral blood study were negative. Aggressive treatment with chemotherapy and external- beam radiation produced complete resolution of solid optic nerve sheath infiltration in both eyes. This report discusses the clinical and ultrasonographic characteristics of CNS malignant B-cell lymphoma with ocular involvement and its differentiation from pseudotumor cerebri. Key Words: Lymphoma- B Cell- Echography- Optic nerve edema. CASE REPORT A 10- year- old Iranian boy was diagnosed with pharyngitis and " abdominal flu" in February 1995. The following month, he developed severe headaches localized over the left ear and occipital area. Two weeks later, he experienced vomiting and developed left lateral rectus paralysis. Magnetic resonance ( MR) angiography and MR imaging scans gave normal results, and a diagnosis of pseudotumor cerebri was made. He was treated with acetazolamide for 5 days with improvement of his symptoms. In April 1995, his headaches became more severe and were associated with numbness of his right hand and transient loss of vision. He was given a 2- week course of acetazolamide, and his symptoms again improved. In May 1995, the headaches returned and acetazolamide treat- Manuscript received September 6, 1996; accepted March 27, 1997. From Cedars- Sinai Medical Center, Los Angeles, California ( A. A. K.) and the Department of Ophthalmology ( B. M. K.), Jules Stein Eye Institute, University of California, Los Angeles, California, U. S. A. Address correspondence and reprint requests to Dr. A. A. Kashani, 436 North Roxbury Dr., Suite 114, Beverly Hills, CA 90210, U. S. A. Presented at the Association for Research in Vision and Ophthalmology ( ARVO) Meeting, Fort Lauderdale, Florida, April 21- 26, 1996. ment was resumed. Family history revealed that the patient's paternal grandmother and maternal aunt had breast cancer. There was a history of familial hypercholesterolemia, which also was present in the child. The patient was an only child, and there was no history of drag toxicity or abnormal skin pigmentation. On physical examination, the patient was somewhat hirsute, intelligent, well- developed ( about 25 kg), and cooperative. Snellen visual acuity was 20/ 25 in either eye. Motility examination showed left lateral rectus paresis. Exophthalmometric study initially gave results of 19 and 20.5 mm, increasing on subsequent examination to 21 and 22 mm in the right and left eyes, respectively. Octopus visual field showed generalized depression. Findings on anterior segment examination were normal. Minimal vitreous cells were present bilaterally in June 1995. The fundi demonstrated extensive optic nerve head elevation despite acetazolamide therapy ( Fig. 1). The nerves were pale, and the elevation appeared to consist of infiltrated cells rather than true papilledema. The vessels overlying the nerves were not engorged, and there was only minimal peripapillary retinal edema. Complete blood count on March 29, 1995, showed the following: segmented neutrophils 39%, lymphocytes 58%, with no atypical cells. Blood lead and vitamin A levels were in the normal range. Cytomegalovirus-specific IgG antibodies suggested recent or past infection. Results of Epstein- Barr body tests indicated current Epstein- Barr virus infection. Three MR imaging studies of the brain yielded normal findings ( Fig. 2). Quantitative standardized orbital echography was performed on June 16, 1995. No evidence for localized orbital mass lesion was seen. In the primary position, the right optic nerve measured 6.14 mm in sheath- to- sheath diameter (> 95th percentile of normals in our laboratory), whereas pia- to- pia diameter was normal at 1.61 mm ( Fig. 3). This is evidence for widening of the optic nerve sheaths. On 30° abduction, sheath- to- sheath diameter decreased to 5.30 mm (> 95th percentile), whereas pia- to- pia diameter remained normal at 1.86 mm ( Fig. 4). Measurement of the left optic nerve showed similar findings. On June 14, 1995, lumbar puncture was performed. Opening pressure was 380 mm H20 ( although the patient was on acetazolamide). Cerebrospinal fluid showed 683 white blood cells/ mm3, mainly immature lymphocytes. Results of two bone marrow aspirates and peripheral 243 244 A. A. KASHANI ETAL. FIG. 1. Grayish pale elevation of left optic nerve. Notice the absence of vascular engorgement, peripapillary edema, or disc hyperemia. blood smear were normal. The diagnosis of central nervous system ( CNS) malignant B- cell lymphoma was confirmed by gene rearrangement on June 6, 1995, and the patient was started on extensive chemotherapy and given 3000 rad of x- radiation. In October 6, 1995, results of funduscopic examination were completely within normal limits in both eyes, with no evidence of residual optic disc edema or infiltration. Repeat echography on October 6, 1995, showed that sheath- to- sheath diameter of the right optic nerve was 4.31 mm, which is within normal limits. Sheath- to- ^*& ^ hk j. i J- \ ^ ' " i * w* i lHt. it/ I * f 11 : / ; 1 1 JSP ? A s- i 11*' J Ml' I! Ten h *. (' M FIG. 3. Standardized A- scan echogram of right optic nerve done June 16, 1995, shows enlarged sheath- to- sheath diameter of 6.14 mm ( long arrows) and normal pia- to- pia diameter of 1.61 mm ( short arrows). sheath diameter of the left optic nerve was 4.74 mm, which is greater than the 95th percentile of normals ( Fig. 5A), decreasing to 3.91 mm on 30 degrees' abduction ( Fig. 5B). This is consistent with the presence of residual fluid in the subarachnoid space. There was no evidence for solid infiltration within or around either optic nerve. The third echogram was done on March 6, 1996, at which time sheath- to- sheath diameter was normal at 3.75 mm OD ( Fig. 6) and 3.97 mm OS. FIG. 2. MR imaging results of brain and orbits on June 20,1995, which were reported to be normal. FIG. 4. On 30 degrees' abduction of right eye ( OD), sheath- to-sheath diameter decreases to 5.30 mm ( long arrow), whereas pia- to- pia diameter remains normal ( short arrows). J Neuro- Ophlhalmol, Vol. 17, No. 4, 1997 MALIGNANT B-FIG. 5. Standardized A- scan echogram of left optic nerve done October 6, 1995. Sheath- to- sheath diameter is 4.74 mm ( A), decreasing to 3.91 mm on 30 degrees' abduction ( B). DISCUSSION Before his being seen by us, this patient was diagnosed with pseudotumor cerebri on the basis of his having headaches, blurred vision, diplopia, signs of left lateral rectus paresis, apparent papilledema, and negative findings on imaging. Initial treatment with acetazolamide produced transient improvement in his symptoms. Pseudotumor cerebri is a diagnosis of exclusion. It is common in women, usually obese, between 30 and 40 years of age, and has been reported in dieting patients ( 1). On lumbar puncture, pseudotumor cerebri shows elevated opening pressure but normal cerebrospinal fluid ( 2). Several factors in the ophthalmic examination findings LYMPHOMA 245 FIG. 6. Standardized A- scan echogram done in March 1996; sheath- to- sheath diameter is now normal at 3.75 mm OD. of our patient were inconsistent with pseudotumor cerebri. Diplopia and left lateral rectus paresis could be caused by this condition, but the progressive proptosis ( left more than right) would be highly unlikely. The presence of vitreous cells is not seen in pseudotumor cerebri and strongly suggests infiltrative neoplasm of the CNS, such as leukemia or lymphoma. The most striking clinical sign that is inconsistent with pseudotumor cerebri was the character of the optic disc elevation. This was extensive bilaterally, but there was minimal surrounding retinal edema. The discs were slightly hyperemic and grayish; however, the amount of elevation was out of proportion to the hyperemia. There was no peripapillary hemorrhage. All of these signs are consistent with infiltration of the nerve sheaths rather than true papilledema. Spontaneous remission of papilledema and sixth nerve palsy is rare but has been reported in acute lymphoblastic leukemia ( 3). The possibility of other infiltrative diseases such as tuberculosis or sarcoid or toxic neuropathy caused by excessive ingestion of vitamin A or lead was ruled out by chest x- ray and medical investigation. Results of MR imaging and MR angiography were normal, leading to a delay in diagnosis and institution of the appropriate therapy. Findings of standardized orbital echography were positive, demonstrating bilateral enlargement of the sheath- to- sheath optic nerve diameter with normal widths of the optic nerves themselves. The widening was shown to result from a combination of solid infiltration with tumor cells and subarachnoid fluid from the elevated intracranial pressure, which was found on lumbar puncture. Thus, ultrasonography and lumbar puncture were the definitive diagnostic tests. The acute lymphoblastic leukemia seen in this child was confined to the CNS and eyes. CNS malignant lymphoma with ocular involvement has a predilection for invasion to the meninges, optic nerve, sub- J Neuro- Ophthalmol, Vol. 17, No. 4, 1997 246 A. A. KASHANIETAL. retinal pigment epithelial space, neurosensory retina, and vitreous cavities and can be mistaken for a variety of conditions, including acute retinitis and vitritis ( 4). Laboratory tests gave positive findings for Epstein- Barr body ( EBV) in this child. As has been shown, EBV is linked to several neoplastic processes including Burkitt's lymphoma, nasopharyngeal carcinoma, posttransplantation lymphoproliferative disease, and non- Hodgkin's lymphoma ( 5). In addition to ocular- CNS lymphoma, systemic leukemia may affect the eye and optic nerve ( 6) or uveal tract ( 7). Central retinal artery occlusion has been described in T- cell lymphoma ( 8). Intravitreal interleukin- 10 levels have been reported to be elevated in a patient with primary ocular lymphoma ( 9). This boy had vitreous cells, but we did not perform vitreous biopsy. Treatment of CNS lymphoma and leukemic conditions is difficult, but extensive radiation therapy and chemotherapy produced remission in our patient. Successfully treated optic nerve infiltration has been previously reported with T- cell lymphoma ( 10). However, there are ophthalmic and CNS complications associated with the treatment of this devastating disease; 13 survivors of childhood acute lymphoblastic leukemia have shown cerebellar hypoplasia and visual- motor deficits in coordination and memory ( 11). REFERENCES 1. Sirdofsky M, Kattah J, Macedo P. Intracranial hypertension in a dieting patient. J Neuroophthalmol 1994; 14: 9- 11. 2. Wall M, George D. Idiopathic intracranial hypertension: a prospective study of 50 patients. Brain 1991; 114: 155- 80. 3. Wolfe GI, Galetta SL, Mollman JE. Spontaneous remission of papilledema and sixth nerve palsy in acute lymphoblastic leukemia. J Neuroophthalmol 1994; 14: 91^ t. 4. Gass DJ, Trattler HL. Retinal artery obstruction and atheromas associated with non- Hodgkin's large cell lymphoma ( reticulum cell sarcoma). Arch Ophthalmol 1991; 109: 1134- 9. 5. Liebowitz D. Epstein- Barr virus: an old dog with new tricks. N Engl J Med 1995; 332: 55- 7. 6. Wallace RT, Shields JA, Shields CL, Ehya H, Ewing M. Leukemic infiltration of the optic nerve. Arch Ophthalmol 1991; 109: 1027. 7. Britt JM, Karr DJ, Kalina RE. Leukemic iris infiltration in recurrent acute lymphocytic leukemia. Arch Ophthalmol 1991; 109: 1456- 7. 8. Cohen RG, Hedges TR in, Duker JS. Central retinal artery occlusion in a child with T- cell lymphoma. Am J Ophthalmol 1995; 120: 118- 20. 9. Chan C, Whitcup SM, Solomon D, Nussenblatt RB. Interleukin- 10 in the vitreous of patients with primary intraocular lymphoma. Am J Ophthalmol 1995; 120: 671- 3. 10. Yamamoto N, Kiyosawa M, Kawasaki T, Miki T, Fujino T, Tokoro T. Successfully treated optic nerve infiltration with adult T- cell lymphoma. J Neuroophthalmol 1994; 14: 81- 3. 11. Ciesielski KT, Yanofsky R, Ludwig RN, et al. Hypoplasia of the cerebellar vermis and cognitive deficits in survivors of childhood leukemia. Arch Neurol 1994; 51: 985- 93. J Neuro- Ophthalmol, Vol. 17, No. 4, 1997 |
