Chapter 29

Cranial Nerve III, IV, and VI Palsies

in the Cancer Patient

Meghan S. Flemmons and Jade S. Schiffman

Abstract Cranial nerve III, IV, and VI palsies in cancer patients can be caused by primary cranial nerve neoplasms, direct extension from brain, brain stem and skull base tumors, direct extension or perineural spread from head and neck tumors, metastases from tumors at distant sites, leptomeningeal disease, and other conditions, including raised intracranial pressure, radiation effect, infection, paraneoplastic syndromes, and certain medications. Ophthalmologic findings in patients with cranial neuropathies depend on the cranial nerve III, IV and VI involved and the location of involvement. Primary cranial nerve neoplasms are most commonly schwannomas. Skull base tumors often result in cranial nerve involvement as well as primary tumors of the breast, lung, and prostate that metastasize to the skull base. Head and neck cancers travel through the skull base and result in cranial nerve involvement. Leptomeningeal disease is a common cause of deficits of cranial nerves II–VII. Other conditions–from treatment of the primary tumor to complications of chemotherapy and immunosuppression–can result in cranial neuropathies.

29.1 Introduction

The presence of cranial nerve (CN) III, IV, and VI paresis in a cancer patient is concerning and requires careful evaluation to determine which nerve is involved, the location of the lesion, and determination if the cranial neuropathy is in fact related to the cancer. Cranial neuropathies in cancer patients can be caused by primary cranial nerve neoplasms, direct extension from brain or brain stem tumors, direct extension or perineural spread from head and neck tumors, metastases from tumors at distant sites, leptomeningeal disease, and other conditions. Neuropathies of cranial nerves III, IV, and VI often present to the neuro-ophthalmology practice.

M.S. Flemmons (B)

Department of Ophthalmology and Visual Sciences, The University of Texas Medical Branch, Galveston, TX, USA

e-mail: meghan.flemmons@duke.edu

Oncology Series 6, DOI 10.1007/978-1-4419-0374-7_29,

C Springer Science+Business Media, LLC 2011

The various mechanisms of these cranial neuropathies in patients with cancer are discussed herein.

29.2 Ophthalmologic Findings with CN III, IV, and VI Palsies

Ophthalmologic findings in patients with cranial neuropathies depend on the cranial nerve involved and the location of involvement. New-onset binocular diplopia is an important symptom indicating the potential of a new cranial neuropathy. An isolated cranial nerve III palsy presents with ptosis, pupil dilation, and an eye that is “down and out”—i.e., an eye with limited motility in elevation, adduction, and depression. A cranial nerve IV palsy presents with subjective torsion, vertical diplopia, and a head tilt. A cranial nerve VI palsy causes horizontal diplopia, a head turn toward the side of the involved nerve, and limited abduction. If multiple cranial nerves are involved, a cavernous sinus lesion is likely, especially if there is involvement of the trigeminal nerve first and second divisions. Proptosis or chemosis may indicate a process involving the orbit or cavernous sinus. Table 29.1 summarizes the various causes of CN III, IV, VI palsies in cancer patients from direct effects of primary and secondary tumors, to those related to the side effects of treatment, immunologic and hypercoagulable states.

Table 29.1 Differential Diagnoses of CN III, IV, VI in cancer patients

and are most often benign, slow-growing tumors. Although the nerves most often affected are the vestibulocochlear, trigeminal, vagal, hypoglossal, and facial nerves, schwannomas may also affect CN III, IV, or VI. Neurofibromas are composed of axons, Schwann cells, and fibroblasts. Hemangiomas are rare lesions that do not often involve CN III, IV, and VI but most commonly affect the vestibulocochlear nerve–facial nerve and optic nerve–optic chiasm complexes.

Supratentorial brain lesions, if confined in this space, will normally not be associated with CN III, IV, or VI paresis unless there is raised ICP causing a false localizing VI nerve paresis. Similarly obstructive hydrocephalus from a supratentorial lesion as in the III ventricle can lead to increased intracranial pressure and CN VI paresis. If the tumor is associated with mass effect it could result in uncal herniation, which may be associated with an ipsilateral CN III paresis, which is usually but not always associated with alteration in consciousness.

Some supratentorial tumors straddle between the supratentorial space and the skull base/brainstem region (eg thalamic tumor and hypothalamic tumors). Thalamic tumors may grow into the infratentorial space by growing directly into the mesodiencephalon and be associated with CN III and IV paresis in addition to components of Parinauds syndrome. Hypothalamic tumors may grow in the suprasellar/retrosellar region and may reach CN III and IV via involvement of the cisterns around the midbrain as well as occasional involvement of the cavernous sinus region.

Infratentorial lesions, intraaxial lesions (e.g., gliomas) can lead to paresis of CN III, IV, and VI nerves and other associated signs.

Skull base tumors often result in cranial nerve involvement (see Chapter 30). Lesions in the petrous portion of the temporal bone and clivus most often manifest with cranial nerve VI palsy [2]. Chordomas are often found in this location and may cause bilateral cranial nerve VI palsies [3]. Sellar and parasellar lesions, such as pituitary tumors, meningiomas or craniopharyngiomas may be associated with neuropathies involving cranial nerves III, IV, V, and VI. Cavernous sinus lesions (e.g., meningiomas) may affect cranial nerves III and IV, the ophthalmic division of cranial nerve V, and cranial nerve VI.

29.4CN III, IV, and VI Palsies due to Metastasis to the Brain, Brain, Stem and Skull Base from Distant Sites

Metastases to brain, brainstem and skull base result in CN palsies may also result in cranial neuropathies. The primary solid tumors that most commonly metastasize to the brain and brainstem include breast, lung, melanoma among others mentioned below. These later tumors may also metastasize to the skull base along with the following tumor types which may have a predilection to the skull base, including prostate,colon, renal, thyroid, lymphoma, leukemias, plasmacytoma, Ewings, osteosarcoma, neuroblastoma and others skull base are breast, lung, and prostate tumors [5, 6].