Man presents with headache, ptosis and abnormal eye movements

Multiple cranial nerve palsies were seen on the patient's third admission to the hospital.

Issue: September 25, 2016

ByErica Liu, MD

ByThomas R. Hedges III, MD

A 49-year-old Brazilian man with no known medical history was admitted to the hospital for headache, ptosis of the right upper eyelid and abnormal eye movements. He had been discharged from the hospital recently with a working diagnosis of migraine, only to be admitted again with worsening symptoms. The admitting team ordered an MRI of the brain that showed a possible cavernous sinus thrombosis. At this point, Ophthalmology was urgently consulted. On review of systems, the patient complained of a bifrontal headache but denied any ocular pain or changes in his vision.

Examination

Uncorrected visual acuity was 20/20 in both eyes. Both pupils were equally round, but the right pupil was sluggish to constriction while the left pupil constricted briskly. There was no afferent pupillary defect in either eye. IOP was within normal limits in both eyes. Confrontation visual fields were full. Extraocular motility was full in the left eye. However, the right eye had significantly limited motility; the patient had limited adduction, elevation and depression in the right eye. The anterior and posterior segments were completely unremarkable in both eyes.

Clinical course

The patient was discharged without a definitive diagnosis but was started on anticoagulation due to the unusual cavernous sinus findings on the MRI. He was also started on steroids for possible Tolosa-Hunt syndrome. His laboratory workup was notable for weakly positive RPR (negative CSF VLDR and treponemal antibody), negative QuantiFERON, normal ACEI and negative HIV. During this time, he missed his follow-up appointment with Ophthalmology. He initially improved on this empiric treatment. However, he began developing worsening headaches and bilateral ptosis. He was admitted 2 weeks later for the third time, and Ophthalmology was consulted again. On exam, both pupils were fixed and mid-dilated. He had a complete third, fourth and partial sixth nerve palsy of the right eye, and the left eye also became involved with a partial third, fourth and partial sixth nerve palsy.

Figure 1. During the patient’s third admission on right, primary and left gaze, there was some abduction in both eyes, exotropia in primary gaze and limited adduction in the right eye more than the left.

Figure 2. Repeat MRI brain post-contrast showing slightly increased and symmetric expansion of both cavernous sinuses.

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Multiple cranial nerve palsies

The differential diagnosis for a patient with multiple cranial nerve palsies and abnormal cavernous sinus findings on MRI (cavernous sinus syndrome) includes cavernous sinus thrombosis, an infiltrative process including lymphoma, metastasis or a granulomatous process. There have been rare reports of neurosyphilis causing multiple cranial nerve palsies. However, he was treated with anticoagulation and did not have any evidence of CNS involvement. Our patient’s history and clinical presentation did not fit with a cavernous sinus thrombosis because he was not acutely ill and did not have risk factors for fungal infection. His visual acuity was good. Also, the globes themselves were white and quiet without additional radiologic findings such as superior ophthalmic vein distension. Granulomatous processes rarely can involve the cavernous sinus. However, his ACEI level was normal, making sarcoid unlikely, and QuantiFERON was negative, ruling out tuberculosis.

Diagnosis and management

Oncology was consulted during this third admission. A CT of the chest, abdomen and pelvis showed multiple soft tissue masses and lymphadenopathy consistent with lymphomatous involvement. At this time, the patient also developed abdominal discomfort and diarrhea. A para-aortic lymph node biopsy was performed and was consistent with Burkitt lymphoma. He also had a lumbar puncture and bone marrow biopsy that confirmed this diagnosis. He was treated with radiation to the base of the skull, intrathecal methotrexate and EPOCH chemotherapy through an Ommaya reservoir. The bilateral ptosis improved, and he regained full extraocular motility of his right eye. Fortunately, his vision remained excellent and unaffected by the disease.

Discussion

Burkitt lymphoma is a non-Hodgkin B-cell lymphoma that is rapidly progressive and fatal if not treated. There are three forms of Burkitt lymphoma: endemic, sporadic and immunodeficiency associated. Sporadic forms typically arise as abdominal masses, presenting with signs of abdominal pain, bowel obstruction, nausea and vomiting. Multiple additional organ systems can be involved, including the kidneys, ovaries, pancreas and bone marrow. Rarely, as in our case, the presenting symptom can be a manifestation of CNS involvement. Workup includes biopsy of the least invasive site. Bone marrow biopsy and lumbar puncture should be performed as involvement may affect treatment decisions. Additional laboratory studies include CBC, CMP (looking specifically for electrolyte abnormalities and liver involvement) and elevated LDH. Imaging studies help stage and assess tumor burden. Patients should be admitted to the hospital for expedited workup and treatment due to the rapid progressive nature of the disease. Tumor lysis syndrome and neutropenic fever are common complications of treatment, and patients should be monitored carefully.

A few cases of Burkitt lymphoma presenting as cavernous sinus syndrome have been reported. As with our patient, these other cases were also treated with steroids initially. In all of these cases, steroids prompted initial regression, which is typical for lymphoma. Symptoms inevitably recur when steroid taper is started, prompting further workup. The prognosis is guarded based on the few case reports; the disease is often recurrent and fatal, although there are reports of near full recovery.

References:
Chang CS, et al. Acta Neurol Taiwan. 2009;18(1):37-41.
Demirkaya M, et al. Pediatr Neurol. 2010;doi:10.1016/j.pediatrneurol.2009.12.008.
Huisman TA, et al. Pediatr Radiol. 2003;doi:10.1007/s00247-003-1010-x.
Kapadia S, et al. IDCases. 2014;doi:10.1016/j.idcr.2014.10.010.
Rasper M, et al. Arch Neurol. 2008;doi:10.1001/archneur.65.12.1668.
Vaphiades MS, et al. J Neuroophthalmol. 2005;25(3):249-250.

For more information:
Erica Liu, MD, and Thomas R. Hedges III, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.
Edited by Jessica Moon, MD, and Emily C. Wright, MD. They can be reached at the New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.