Nasopharyngeal Carcinoma Presenting as Third Nerve Palsy

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1University of Tennessee Health Science Center, School of Medicine, Memphis, Tennessee
2Department of Neurology, University of Tennessee Health Science Center, Memphis, Tennessee

Anderson-Quiñones C, Khan K, Khedkar S, Patel J, Wilner A. Nasopharyngeal carcinoma presents as a tertiary nerve palsy. consultant. Published online January 30, 2023. doi:XX

Accepted May 23, 2022. Accepted November 16, 2022.

The authors report no relevant financial relationships.


Catherine Anderson-Quiñones, BM, University of Tennessee Health Science Center, College of Medicine, 920 Madison Avenue, Memphis, TN 38163 ([email protected])

case presentationOur patient was a 48-year-old man who complained of headache, left eye ptosis, dilated pupils, and tooth pain for 10 days.

Medical historyOur patient had a history of hypertension and poorly controlled type 2 diabetes.

Physical examination. Physical examination revealed only cachexia and elevated blood pressure of 181/104 mm Hg. The best corrected visual acuity was 20/30 in both eyes on the Snellen chart. Intraocular pressure was within normal limits. Cranial nerve examination revealed ptosis and anisocoria in the left eye. The right pupil was responsive at 2 mm and the left pupil was minimally responsive at 3 mm. There was no relative afferent pupillary defect. The left eye had medial and inferior gaze limitation.

diagnostic test. Consultation with an ophthalmologist confirmed left third nerve palsy, raising the possibility of concomitant fourth nerve palsy. Other neurological examinations were within normal limits, including speech and swallowing. Notable laboratory abnormalities were platelets 86,000 mcL, glucose 358 mg/dL, and HbA1C 13.4%.

Because the differential diagnosis of isolated cranial nerve palsy differs significantly from multiple cranial nerve palsy, it is possible that the 4th cranial nerve was involved in complex medical decision-making. Initial brain computed tomography (CT), brain CT angiography, brain CT venography, non-contrast magnetic resonance imaging (MRI), and magnetic resonance venography were interpreted to be within normal limits. His CT angiography of the neck showed a 50% narrowing of the cone of the left internal carotid artery. This stenosis was initially thought to result from atherosclerosis, which was plausible given the patient’s risk factors for atherosclerosis, hypertension and uncontrolled diabetes. . Isolated third cranial neuropathy is the most common symptom of diabetic cranial neuropathy.1

A lumbar puncture was performed to look for evidence of carcinomatosis, infection, or subarachnoid hemorrhage. The patient’s cerebrospinal fluid was clear and colorless, with 1 white blood cell, 1 red blood cell, glucose 127 mg/dL, protein 50 mg/dL, and bacterial culture negative.

Initial neuroimaging studies were reported negative. However, a later review of the CT images revealed erosion of the left carotid canal consistent with an invasive tumor (Figure 1).

Figure 1. The patient’s initial head CT scan showed enlargement of the left carotid canal (arrow), which was initially interpreted by radiography as within normal limits.

Identification of this invasive malignancy required both CT and MRI scans, including the use of contrast agents. A contrast-enhanced brain MRI eventually showed a mass lesion in the cavernous sinus (Figure 2).

Figure 2

Figure 2. This axial T1 MRI post-enhancement shows more clearly the suspicious soft-tissue mass in the left cavernous sinus (arrow).

A fine-needle aspiration biopsy of enlarged left cervical lymph nodes was performed in consultation with an otorhinolaryngology specialist. Histopathological diagnosis was metastatic nonkeratinizing squamous Epstein-Barr virus-positive carcinoma.

treatment and managementThe patient was treated with induction chemotherapy followed by concurrent chemoradiation in an outpatient setting.

Patient Outcomes and Follow-upAfter treatment, the patient’s symptoms and cranial nerve palsy resolved. Follow-up brain MRI and positron emission tomography scans showed no evidence of disease. Had neoplasms not been considered as the cause of this third nerve palsy, this patient might have had a poor prognosis, rather than a full recovery, due to the lack of definitive treatment. .

Differential diagnosisThe differential diagnosis of acute third nerve palsy is broad and includes aneurysm, diabetes (microvascular), migraine, Miller-Fischer syndrome, stroke, surgery, trauma, tumors, and many others.2 Differential diagnosis of the third nerve palsy depends on whether it is isolated. A practical diagnostic algorithm is presented by Bruce and his colleagues.3

Careful evaluation of symptoms may suggest localization of the lesion. For example, oculomotor nerve palsy with isolated muscle involvement is most likely due to ischemic microvascular lesions. In contrast, those with pupillary lesions suggest a compressive lesion such as an aneurysm.Four Aneurysms that cause third nerve palsy rarely leave the pupil. For example, in a series of 143 third nerve palsies due to aneurysm, only 2% spared the pupil.2 The presence or absence of other cranial nerve dysfunction also guides the investigation.3

Ischemic microvascular etiology is the most common cause of oculomotor nerve palsy.3 This etiology is not surprising in this patient with known hypertension and poorly controlled diabetes.Five The patient complained of headache and tooth pain, but no eye pain. MRI may show nerve thickening and enhancement in diabetic oculomotor palsy, but this only occurs in about two-thirds of cases.6 It was unclear whether the secondary cranial neuropathy resided in the trochlear nerve. If so, ischemic microvascular etiology is unlikely, as multiple simultaneous acute diabetic neuropathies are rare. In the largest review article to date, the most common etiology of multiple cranial nerve palsy was tumors, responsible for approximately 30% of cases.7 Therefore, timely work-up to confirm or rule out a tumor diagnosis should be considered in patients with multiple cranial nerve palsy.

Nasopharyngeal cancer is a relatively common tumor of the head and neck. They are more likely to cause cranial nerve palsy than other tumors in this region, with up to 29% of cases of neuropalsy.8,9 When cranial nerves are involved, cranial nerves V (38%), VI (26%), and XII (11%) are most commonly affected. A third neuropathy has been reported, but is unusual.9 In fact, Leung and colleagues8 reported that cranial nerve III lesions never appear alone. As a result, nasopharyngeal carcinoma was not high in the initial differential diagnosis.

discussion. The oculomotor nerve controls lens accommodation, pupil contraction, and the simplest eye movements.Four Oculomotor nerve lesions can affect some or all of these functions, depending on their severity and location. Due to the location of our patient’s tumor and its subtle appearance on CT images, it was initially overlooked. Physical examination features such as left eye ptosis, anisocoria, and cachexia were essential to identify the site of cranial nerve involvement and etiology.

Acute third nerve palsy increases the likelihood of a neurological emergency. Third nerve palsy must be diagnosed accurately because it can be a sign of intracranial aneurysm, pituitary stroke, or temporal arteritis.3 Third nerve palsy with headache and pupillary defect increases the likelihood of cerebral aneurysm. This is because an aneurysm can compress the ipsilateral 3rd nerve superficial pupillary motor fiber and its blood supply.3 Although aneurysms cause only a minority (6-10%) of third nerve palsy, such aneurysms are life-threatening and prone to rupture, requiring immediate diagnosis and treatment.2,5 In our case, neuroimaging, including digital angiography, the gold standard of diagnosis,Ten did not reveal signs of aneurysm.

This patient’s presentation is unusual because there was isolated third cranial nerve involvement in the cavernous sinus without orbital involvement. To our knowledge, the only other case reported in the literature is unilateral isolated third cranial nerve palsy and one reported with similar presentation of anatomical involvement.11

ConclusionPhysicians must consider a wide range of diagnoses when faced with a patient presenting with headache and acute third nerve palsy. Our case is a rare example of oculomotor nerve palsy secondary to locally invasive nonkeratinizing nasopharyngeal carcinoma. In our patient, acute third nerve palsy was caused by invasive nasopharyngeal carcinoma, a rare manifestation of this tumor. Diagnosis was largely overlooked despite adequate brain CT scan, MRI, digital angiography, and phlebography. Reporting this case highlights how locally invasive carcinoma should be maintained in the differential diagnosis of patients presenting with isolated third nerve palsy. If the diagnosis is not clear, it may be beneficial to reexamine the radiology for subtle abnormalities that may have been overlooked or misunderstood. In this case, the stenosis of the left carotid artery was incorrectly attributed to atherosclerosis rather than tumor compression. The diagnosis of microvascular third nerve palsy suggested by routine neuroimaging should not be made until less common and potentially life-threatening etiologies, such as invasive tumors, are considered. .

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