Cavernous sinus syndrome Rakul Nambiar, MD, and Sreejith G. Nair, DM
Cavernous sinus syndrome (CSS) is a condition characterized by multiple cranial nerve palsies manifesting with ophthalmoplegia, ptosis, and facial sensory loss due to involvement of adjacent cranial nerves. Tumors, trauma, and vascular, infectious, and noninfectious inflammatory disorders have all been described as causes. Lymphomas have been reported to involve the cavernous sinus, both as primary cavernous sinus lymphomas or as secondary lesions. Here, we describe the case of a 63-year-old-man with untreated chronic lymphocytic leukemia (CLL), diagnosed 4 years earlier, who presented with CSS. Our patient underwent standard chemotherapy, but he succumbed to infection during the neutropenic period.
eoplastic B-cell inﬁltration in chronic lymphocytic leukemia (CLL) has been described in skin, lung, pleura, kidney, and gastrointestinal tract tissues. However, involvement of the central nervous system (CNS) is very rare (1), and symptomatic CNS involvement in CLL is known to be rarer (1). Reported cases of CNS involvement in CLL have demonstrated a diverse and nonspeciﬁc spectrum of symptoms: headaches, mental status changes, cerebellar signs, cranial nerve abnormalities, and weakness of extremities (1). Here we report an unusual case of a patient with untreated CLL who presented with cavernous sinus syndrome (CSS). To the best of our knowledge, CLL causing CSS has not been reported previously. CASE REPORT A 63-year-old man presented with double vision. He ﬁrst noticed diplopia 2 months prior to evaluation, stating it waxed and waned in intensity. One month later, he had recurrent severe diplopia, most prominent on leftward gaze, accompanied by nausea, headache, and photophobia. His symptoms persisted and progressed to include left-sided eyelid heaviness 1 month after presentation. He had a 4-year history of asymptomatic Rai stage I CLL (lymphocytosis with lymphadenopathy, without organomegaly or cytopenia). He was on regular follow-up during the 4 years with blood counts, along with clinical examination at 3-month intervals. On examination, his Eastern Cooperative Oncology Group performance score was 2. Neurological exam revealed left ptosis, sluggish pupillary reﬂex, lateral gaze palsy, diminished medial Proc (Bayl Univ Med Cent) 2017;30(4):455–456
gaze, and limited intorsion of the left eye. Visual acuities were 6/6 in the right eye and 6/9 in the left eye. Dilated fundus examination was normal. The left corneal reﬂex was absent, and he also had hypoesthesia in the territory of the ﬁrst and second divisions of the right trigeminal nerve. In addition, multiple cervical lymph and axillary nodes were palpable, and the spleen was palpated 2 cm below the left costal margin. The rest of the neurological and physical examination was unremarkable. The white blood cell count was 108,000/μL, and a peripheral blood smear revealed 60% atypical lymphocytes. His hemoglobin level was 11.5 g/dL and platelet count, 163,000/μL. His lactate dehydrogenase level was 736 IU/L (normal range, 313–618 IU/L). Peripheral blood ﬂow cytometric analysis was diagnostic of CLL. Bone marrow aspiration revealed 60% small atypical lymphoid cells, and bone marrow biopsy showed interstitial and nodular inﬁltration by atypical lymphoid cells, having clumped chromatin among normal hematopoietic elements. Fluorescence in situ hybridization (deletion 11q, deletion 13q, and deletion 17p) and conventional cytogenetic analysis of the peripheral blood did not reveal any abnormalities. Magnetic resonance imaging (MRI) of the patient’s brain revealed an asymmetric enhancing lesion in the left cavernous sinus, encasing the carotid artery and extending to the trigeminal cave (Meckel’s cave) (Figure). These ﬁndings were suggestive of neoplastic inﬁltration of the left cavernous sinus. A diagnostic lumbar puncture was performed, and cerebrospinal ﬂuid (CSF) revealed a white blood cell count of 20 leukocytes/mm3 (lymphocytes, 80%; neutrophils, 20%), glucose of 80 mg/dL, and total protein of 54 mg/dL. Cytological examination demonstrated the presence of small monomorphic lymphocytes in the CSF suggestive of CLL cells. The patient received high-dose methylprednisolone and was started on ﬂudarabine (25 mg/m2/day intravenously for the ﬁrst 3 days), cyclophosphamide (250 mg/m2/day intravenously for the ﬁrst 3 days), and rituximab (375 mg/m2/day intravenously on day 1) (FCR regimen). He improved symptomatically after steroids; however, his status worsened after chemotherapy and he From Regional Cancer Centre, Trivandrum, India. Corresponding author: Sreejith G. Nair, DM, Department of Medical Oncology, Regional Cancer Centre, Trivandrum 695011, India (e-mail: [email protected]
CLL are heterogeneous and include headache, cranial nerve palsies, cerebellar signs, visual problems, and motor and/or sensory deﬁcits. Imaging studies are neither speciﬁc nor sensitive in the detection of CNS involvement; the diagnosis is usually conﬁrmed by lumbar puncture. At present, there are no established guidelines for treatment of CLL patients with CNS involvement. Most patients have been treated with intrathecal chemotherapy with or without radiation therapy or systemic chemotherapy (1). Intrathecal rituximab has been found Figure. MRI of the brain with contrast, (a) axial view and (b) coronal view, showing asymmetric enhancing thickening to be eﬀective in aggressive B-cell lymphomas; however, its eﬃcacy in in the left cavernous sinus (arrow). CLL has not been assessed (9). For CLL patients with leptomeningeal disease, ﬂudarabine-based developed sepsis during the neutropenic period. He died on therapy has been found to be eﬀective and may be a favorable postchemotherapy day 12. therapeutic option (10). In our patient, a combination of ﬂudarabine, cyclophosphamide, and rituximab (FCR regimen) was DISCUSSION very toxic, and he succumbed to sepsis during the neutropenic Cavernous sinus syndrome is characterized by ophthalperiod. moplegia and sensory deﬁcits over the head due to combined deﬁcits of the three cranial nerves (third, fourth, and sixth) 1. Lopes da Silva R. Spectrum of neurologic complications in chronic lymresponsible for eye movements and pupil function, and at least phocytic leukemia. Clin Lymphoma Myeloma Leuk 2012;12(3):164–179. one branch of the trigeminal nerve. The wide-ranging types of 2. Nakatomi H, Sasaki T, Kawamoto S, Fujimaki T, Furuya K, Kirino T. pathologies that involve the cavernous sinus can be classiﬁed as Primary cavernous sinus malignant lymphoma treated by gamma knife tumoral, congenital, infectious, inﬂammatory, granulomatous, radiosurgery: case report and review of the literature. Surg Neurol and vascular. 1996;46(3):272–278. 3. Arimoto H, Shirotani T, Nakau H, Hashizume K, Sakai Y, Matsukuma S. Among the tumors involving the cavernous sinus, head and Primary malignant lymphoma of the cavernous sinus—case report. Neurol neck tumors are the most likely to metastasize to the cavernous Med Chir (Tokyo) 2000;40(5):275–279. sinus. The other common primary sites in patients with cavern4. Sadruddin S, Medeiros LJ, DeMonte F. Primary T-cell lymphoblastic ous sinus metastases are breast, lung, and prostate. Lymphomas lymphoma of the cavernous sinus. J Neurosurg Pediatr 2010;5(1):94–97. have been reported to involve the cavernous sinus, as primary 5. Ceyhan M, Erdem G, Kanra G, Kaya S, Onerci M. Lymphoma with bilateral cavernous sinus involvement in early childhood. Pediatr Neurol lymphomas (2–4) or as secondary lesions, and may occur as 1994;10(1):67–69. unilateral or bilateral lesions (5, 6). Lymphomas may involve 6. Huisman TA, Tschirch F, Schneider JF, Niggli F, Martin-Fiori E, Willi the cavernous sinus as a result of invasion or metastasis origiUV. Burkitt’s lymphoma with bilateral cavernous sinus and mediastinal nating in the head and neck region, or metastasis of systemic involvement in a child. Pediatr Radiol 2003;33(10):719–721. origin. Burkitt lymphoma (6), diﬀuse large B-cell lymphoma 7. Hirano H, Tashiro Y, Fujio S, Goto M, Arita K. Diﬀuse large B-cell lymphoma within a cavernous hemangioma of the cavernous sinus. Brain (7), T-cell lymphoblastic lymphoma (4), and diﬀuse small B-cell Tumor Pathol 2011;28(4):353–358. lymphoma (8) have all been reported as primary lymphoma and 8. Delpassand ES, Kirkpatrick JB. Cavernous sinus syndrome as the presenas metastases in the cavernous sinus, but to our knowledge CLL tation of malignant lymphoma: case report and review of the literature. involvement has never been reported in the literature. Infectious Neurosurgery 1988;23(4):501–504. causes such as fungus and tuberculosis were considered because 9. Rubenstein JL, Fridlyand J, Abrey L, Shen A, Karch J, Wang E, Issa S, of the immunocompromised status of our patient. However, Damon L, Prados M, McDermott M, O’Brien J, Haqq C, Shuman M. Phase I study of intraventricular administration of rituximab in paan infectious cause was less likely in our patient, in view of the tients with recurrent CNS and intraocular lymphoma. J Clin Oncol presence of CLL cells in the CSF. Moreover, the CSF culture 2007;25(11):1350–1356. was negative. 10. Knop S, Herrlinger U, Ernemann U, Kanz L, Hebart H. Fludarabine may CNS involvement of CLL remains a poorly studied pheinduce durable remission in patients with leptomeningeal involvement of nomenon. The clinical manifestations of CNS involvement in chronic lymphocytic leukemia. Leuk Lymphoma 2005;46(11):1593–1598. a
Baylor University Medical Center Proceedings
Volume 30, Number 4