Neurologic Disorders

Ptosis, Anisocoria Point Toward Horner's, Lung Tumor

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A 65-year-old black male was diagnosed with Horner's syndrome, an interruption of the oculosympathetic nerve supply. He also was diagnosed with a Pancoast tumor in the right lung apex. The patient underwent surgery and radiation to eradicate the tumor, but has been lost to follow-up.

History and Findings
The patient presented for an automated visual field. As we updated his history, he complained of pain and burning in the right eye and a right "droopy" lid that seemed to worsen over the last 6 weeks.

The patient denied a history of trauma or surgery, and his general medical and ocular histories were noncontributory. Social history was remarkable for smoking 2-3 packs of cigarettes a week for 45 years.

Best-corrected visual acuity was 20/25 O.U. at distance and near. External examination revealed an anisocoria (2mm OD, 3mm O.S.) that was noticeably worse in dim illumination (2.5mm OD, 4mm O.S.). There was no afferent pupillary defect.

The interpalpebral fissure of the right eye measured less than that of the left (6mm OD, 11mm O.S.). Extraocular muscles, color vision and cover testing were normal.

Refraction revealed hyperopia with astigmatism correctable to 20/25 at distance and near. The slit lamp exam was normal in both eyes. IOPs were 14mm Hg O.U. The dilated fundus examination revealed cup-to-disc ratios of .45/.45 OD, 50/.50 O.S.

We referred the patient to a neuro-ophthalmology clinic to rule out Horner's syndrome.

Diagnosis
The neuro-ophthalmologist confirmed our suspicion of Horner's syndrome with the 10% cocaine test. Since the patient had a history of smoking and a worsening raspy voice, the neuro-ophthalmologist ordered a CT-scan of his chest to rule out a lung apex lesion. The CT disclosed a Pancoast tumor at the right lung apex.

Treatment and Follow-up
The neuro-ophthalmologist referred the patient to an oncology team for treatment. The patient underwent surgery and radiation to eradicate the tumor. We initially followed him at 4-month intervals, but he has since been lost to follow-up.

Discussion

Horner's syndrome is characterized by an interruption of the oculosympathetic nerve supply somewhere between its origin in the hypothalamus and the eye. Claude Bernard first noted the condition experimentally in 1852, followed by Swiss ophthalmologist Johann Friedrich Horner in 1869.^1-4

Horner's syndrome has no predilection for age, race or gender. The syndrome may be congenital or present later in life. Congenital cases present around age 2 with heterochromia and absence of a horizontal eyelid fold or crease in the ptotic eye. Iris pigmentation, which is under sympathetic control during early childhood development, is completed by age 2. For this reason, heterochromia is an uncommon finding in Horner's syndrome acquired later in life.^1,2 Old photographs can help you distinguish congenital Horner's by documenting heterochromia that was present at birth.

If a patient presents with recent onset ptosis, your first suspicion should include cranial third-nerve palsy. Even if there is no complaint of diplopia, this entity should be considered. In some instances, the ptotic eyelid can block vision sufficiently to prevent the perception of diplopia. If palsy is not present and you observe anisocoria that's exaggerated in dim illumination, then Horner's syndrome is the likely cause.

Pharmacological testing is then necessary to confirm the diagnosis and localize the lesion.^5-12 To confirm the presence of Horner's, apply one drop of a topical 10% cocaine solution to both eyes. This solution acts as an indirect sympathomimetic agent. It causes the normally innervated pupil to dilate by inhibit- ing the re-uptake of norepinephrine at the nerve ending.

Evaluate the test 15-30 minutes after instilling the drops to ensure accuracy. Eyes that fail to dilate or that dilate poorly have Horner's syndrome.

Next, you should determine whether the lesion is pre- or postganglionic using Paredrine 1% (hydroxyamphetamine) or Pholedrine 5% (n-methyl derivative of hydroxyamphetamine). Since cocaine can inhibit the uptake of these two medicines and reduce accuracy, you should wait 24-48 hours after the cocaine test before instilling either of these two agents. These agents release the endogenous neurotransmitter norepinephrine from the presynaptic vesicles. At the end of each neuron you need some sort of action; it's where electrical impulse is converted to a chemical impulse, which makes something happen. If there's third-neuron damage, the pupil will not dilate, indicating a postganglionic lesion.

Most researchers agree that preganglionic lesions are less common but more ominous, because they are often indicative of infarct, cancer, infection or stroke.^1,2,10,13

Etiologies of Horner's syndrome include cluster migraines, trauma, cerebral vascular accident, cavernous sinus lesion, infections, aortic dissection, carotid dissection and (as in this patient) Pancoast tumor. (For other causes, see table of causes.)

Pancoast tumor, or superior pulmonary sulcus carcinoma, was first described in 1924 by H.K. Pancoast. A true Pancoast tumor usually extends through the visceral pleura into the parietal pleura and chest wall. It's histopathology is epithelial in nature, but its exact origin remains uncertain.^13-16

Signs and symptoms of Pancoast tumor include shoulder pain, loss of limb function, atrophy of the hand muscles, Horner's syndrome, and hypoesthesia in the upper chest.^13-16

Despite its small size and general lack of metastasis, Pancoast tumor has a rapid and almost universal mortality rate. Risk factors include smoking and exposure to various contaminants (asbestos, radon gas, uranium, arsenic fumes, isopropyl oil, nickel, metallic iron, iron oxide, and beryllium).^13-16

A combination of radiation followed by surgical resection of the tumor is the preferred treatment of Pancoast tumor. One study found that patients treated with this method did not survive significantly longer than patients who underwent radiation alone, but the authors say that only a small number of patients underwent both radiation and surgery.¹⁷ Yet another study found that median survival was 21.6 months, and another found that 5-year survival rates ranged from 30-50%.^18-19

This case presents some valuable lessons. Never make hasty assumptions. Use the knowledge you've accumulated to fully investigate clinical presentations. This patient's condition may have been mistaken for a cranial nerve palsy. Additional findings, however, warranted further testing, leading to the diagnosis of Horner's syndrome. Once testing confirmed this diagnosis, we needed further assessment to determine any systemic causes. We can only hope the patient sought treatment elsewhere after he was lost to follow-up.

Dr. Gurwood is associate professor of clinical sciences at Pennsylvania College of Optometry. Dr. Terrigno is completing a residency there. Dr. Tran serves in the U.S. Air Force.

Posted: Oct. 20, 2000. Originally published March 2000.

Pathophysiology of Horner's Syndrome

Sympathetic innervation to the eye consists of a three-neuron arc:10-12,20 First neuron. This originates in the dorsolateral hypothalamus, descends through the reticular formation of the brainstem and travels to the spinal chord. It synapses with second-order neurons between the eighth cervical and fourth thoracic vertebrae.

Second-order neurons. Axons from these exit the spinal cord, pass over the apex of the lung and synapse in the superior cervical ganglion of the sympathetic chain in the neck.

Third-order neurons. The postganglionic axons from these course from the neck to the eye with the internal carotid artery via the cavernous sinus. Fibers from these axons form the long and short posterior ciliary nerves of the eye. Interruption anywhere along this pathway-preganlionic (first or second neurons before synapse in the superior cervical ganglion) or postganglionic (after exiting the superior cervical ganglion)-will induce an ipsilateral Horner's syndrome.

Pharmacological Diagnosis and Localization of Horner's

Causes of Horner's Syndrome

Footnotes

1. Giles CL, Henderson JW. Horner's syndrome: an analysis of 216 cases. Am J Ophthalmol 1958;46(3):289-96.
2. Wilkins RH, Brody IA, Durham NC. Horner's syndrome. Arch Neurol 1968;19:540-2.
3.Tantum LA. Pupil anomalies. In: Onofrey BE, ed. Clinical Optometric Pharmacology and Therapeutics. Philadelphia: J.B. Lippincott Co. 1991;13:1-13.
4. Burde RM, Savino RJ, Trobe JD. Anisocoria and abnormal pupillary light reaction. In: Burder, RM, Savino PJ, Trobe JD, eds. Clinical Decisions in Neuro-ophthalmology. 2nd ed. St. Louis: Mosby Year Book Inc. 1992:321-46.
5. Oosterhuis HJGH. Acquired blepharoptosis. Clinical Neurology and Neurosurgery 1996;98:1-7.
6. Maloney WF, Younge BR, Moyer NJ. Evaluation of the causes and accuracy of pharmacologic localization in Horner's syndrome. Am J Ophthalmol 1980;90:394-402.
7. Bates AT, Chamberlain S, Champion M, et. al. Pholedrine: a substitute for hydroxyamphetamine as a diagnosis eye drop test in Horner's syndrome. J Neurology, Neurosurgery and Psychiatry 1995;58:215-7.
8. Thompson HS, Pilley SFJ. Unequal pupils: a flow chart for sorting out the anisocorias. Survey Ophthalmol 1976;21(1):45-8. Isn't this common knowledge now??)
9. Kanski JJ. Neuro-ophthalmology. In: Kanski, JJ ed. Clinical Ophthalmology. A Systemic Approach. 3rd ed. Oxford, England: Butterworth-Heinemann Ltd. 1994:466-7.
10. Cullom RD, Chang B. Neuro-ophthalmology. In: Cullom RD, Chang, B, eds. The Wills Eye Manual. 2nd ed. Philadelphia: J.B. Lippincott Co. 1993:241-6. (later edition available!)
11. Wilhem H, Wilhem B, Kriegbaum C. Interaction of the indirectly acting topical sympathomimetics cocaine and pholedrine. German J Ophthalmol 1996;5:168-70.
12. Donahue SP, Lavin PJM, Digre K. False-negative hydroxyamphetamine (Paradrine) test in acute Horner's syndrome. Am J Ophthalmol 1996;121(6):900-1.
13. Pancoast HK. Superior pulmonary sulcus tumor. JAMA 1932;99:1391-6
14. Urschel HC. New approaches to Pancoast and chest wall tumors. Chest 1993;103:360S-361S.
15. Sartori F, Rea F, Calabro F, et. al. Carcinoma of the superior pulmonary sulcus. J ThoracCardiovasc Surg 1992;104:679-83.
16. Taylor LQ, Williams AJ, Santiago SM. Survival in patients with superior pulmonary sulcus tumors. Respiration 1992;59:27-9.
17. Millar J, Ball D, Worotniuk V, Smith J., et. al. Radiation treatment of superior sulcus lung carcinoma. Australas Radiol 1996;40(1):55-60.
18. Attar S., Krasna MJ, Sonnett JR, et. al. Superior sulcus (Pancoast) tumor: experience with 105 patients. Ann Thorac Surg 1998;66(1):193-8.
19. Johnson DE, Goldberg M. Management of carcinoma of the superior pulmonary sulcus. Oncology (Huntingt) 1997;11(6):781-6.
20. Polinsky RJ, Martin JB. Disorders of the autonomic nervous system. In: Isselbacher KJ, Braunwald E, Wilson JD, et. al., eds. Harrison's Principles of Internal Medicine. 3rd ed. Vol.2. New York: McGraw-Hill Inc. 1994:2344-52.