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Show Journal of Clinical Neuro-ophthalmology 13(4): 250-253, 1993. Herpes Zoster Ophthalmicus as a Cause of Horner Syndrome Edward F. Smith, M.D., Leo Santamarina, M.D., and Arthur H. Wolintz, M.D. © 1993 Raven Press, Ltd., New York Herpes zoster ophthalmicus is a disease in which the varicella-zoster virus replicates and produces inflammation in the skin of the face supplied by the sensory branches of the ophthalmic division of the trigeminal nerve. It can also cause a conjunctivitis, keratitis, uveitis, extraocular muscle paralysis, and acute retinal necrosis. We found only a single report of this disease as a cause of Horner syndrome. Here we report a case of herpes zoster ophthalmicus that progressed to a sixth nerve palsy and, subsequently, a Horner syndrome. We discuss how the anatomic relationship of the fifth, sixth, and sympathetic nerves in the cavernous sinus provides a route whereby the varicella-zoster virus may produce a Horner syndrome. To our knowledge this is the first fully documented case of Horner syndrome caused by herpes zoster ophthalmicus. Key Words: Varicella-zoster virus-Cranial nervesSympathetic nerves-Miosis. From the Department of Ophthalmology, State University of New York, Health Science Center at Brooklyn, Brooklyn, New York, U.S.A. Each author states that he has no financial or proprietary interest in any of the pharmaceutical products mentioned in the article. Address correspondence and reprint requests to Dr. Edward F. Smith, Downstate Ophthalmology Associates, 11 Plaza Street, Brooklyn, New York 11217, U.s.A. 250 The varicella-zoster virus is a DNA virus that causes chickenpox during primary infection. The virus remains latent for years in the sensory ganglia, becomes reactivated by unknown mechanisms, and travels peripherally via the sensory nerves subserving the ganglion in which reactivation has taken place. The first division of the trigeminal nerve is frequently involved. The lids, conjunctiva, sclera, cornea, uvea, and retina have been reported to be affected by the virus (1,2). Impairment of extraocular motility has been documented, as well (3). Horner Syndrome, however, has only been reported once before in association with herpes zoster ophthalmicus (4). CASE REPORT A 53-year-old man presented with a 5-day history of a vesicular rash about the right periorbital region and eyelid. He denied any significant medical problems or drug allergies and acknowledged an episode of varicella during childhood. A diagnosis of herpes zoster ophthalmicus was made and he was started on acyclovir 200 mg by mouth five times a day. Within 2 days he had developed three dendritic corneal lesions, which stained with fluorescein. He did not have a Hutchinson's sign and the remainder of his ocular examination was unremarkable. The acyclovir was increased to 800 mg five times a day, and bacitracin and cyclopentolate four times a day were started as well. At 14 days later his skin and corneal lesions had resolved considerably, but he now manifested a right abduction deficit. Prednisone 60 mg daily and cimetidine 300 mg four times a day were started in addition to the above medications. Computed tomography (CT) sc~n with contrast of the head and orbits was negative. At 21 days later the prednisone was tapered, the acyclovir had been stopped, and the right sixth HERPES ZOSTER OPHTHALMICUS 251 nerve palsy was improving. The pupil examination at this time revealed miosis of the right eye (Fig. 1) with increased disparity in pupillary size during dark adaptation. Cocaine 4% was instilled in both eyes; however, the right pupil failed to dilate after 1 hour (Fig. 2). Hydroxyamphetamine testing performed on a subsequent visit 1 week later revealed the same pupillary findings as the cocaine testing, thus a third-order neuron lesion was documented. The triad of true Horner syndrome was confirmed by placing a bright light in front of the patient's face for a few minutes and noting the right side to be objectively and subjectively anhydrotic compared to the left side. One month later the patient had discontinued all medications and, although the ptosis and miosis persisted, the skin, cornea, and sixth nerve lesions had resolved. DISCUSSION Although herpes zoster commonly affects the trigeminal nerve and, less commonly, the third and sixth nerves, it rarely causes a Horner syndrome. A recent and thorough review of herpes zoster did not mention Horner syndrome as a complication (1). In 1958 a retrospective analysis of 216 cases of Horner syndrome revealed only one case in which ophthalmic zoster was found to be the cause (4). This case was mentioned as one in a long list of other causes but was not described in any detail. Our search of the literature revealed only two other case reports of zoster which had resulted in a Horner syndrome, neither of these involving the ophthalmic division of the fifth nerve. In the first case the sensory distribution of the seventh nerve along with the maxillary and mandibular branches of the fifth nerve displayed the typical weeping vesicular eruption of herpes zoster, but the ophthalmic division was spared (5). This patient had miosis and ptosis but no anhydrosis on the af-fected side of the face. The second report involves a patient with zoster of the second and third thoracic dermatomes who also manifested the full Horner's triad (6). In this patient also the zoster spared the ophthalmic nerve. Parkinson postulated that there are two as yet unrecognized syndromes, which he was surprised had never been documented given the intimate relationship between the fifth nerve, sixth nerve, and sympathetic nerves within the cavernous sinus (7). The first involved a lesion along the sixth nerve where it is accompanied by the sympathetic nerves, and the second involved a lesion in the first division of the fifth cranial nerve beyond where it is joined by the sympathetic nerves. Each lesion would result in all or part of a Horner syndrome in addition to a sixth nerve palsy in the first case and a sensory deficit within the distribution of the first division of the fifth cranial nerve in the second case. We have identified a patient in whom herpes zoster ophthalmicus has resulted in a syndrome involving the sympathetic nerves, the sixth nerve, and the first division of the fifth cranial nerve. We postulate that the anatomic relationship of the trigeminal, abducens, and sympathetic nerve fibers as they course through the cavernous sinus (8,9) accounts for the progression of our patient's illness. As the sympathetic nerve runs with the carotid artery, it lies just medial to the sixth nerve, which in turn is medial to the fifth nerve as it travels along the lateral wall of the cavernous sinus. In the cavernous sinus the sympathetic nerve joins the abducens nerve briefly before joining the ophthalmic branch of the trigeminal nerve (10,11). Hence it is not difficult to account for the order in which the nerves were affected in our patient. Ocular pathologic studies of eyes infected by the varicella-zoster virus have shown severe granulomatous and nongranulomatous inflammation of virtually every ocular tissue, including the blood FIG. 1. Healing herpetic lesions on the right forehead as well as ptosis and miosis of the right eye. J Clin Neuro-ophthalmol. Vol. 13. No.4. 1993 252 E. F. SMITH ET AI. FIG. 2. The same patient shown in Fig. 1 after administration of cocaine drops to each eye. vessels (12). The pathologic changes range from a mild inflammatory response limited to one tissue to a severely destructive process affecting multiple tissues with hemorrhage and necrosis. While the varicella-zoster virus typically replicates and travels peripherally via the sensory nerves, it is also capable of lateral spread from one inflammed nerve or satellite cell to adjacent tissues (13). This lateral spread has been postulated to occur within the sensory ganglia. If this process occurred in the peripheral nerve fibers, then the replicating virus would be capable of spreading from the fifth nerve to the adjacent sixth and sympathetic nerves. Given that the replicating virus and the subsequent inflammatory response is responsible for such severe complications, treatment must be directed first at the virus and second at the symptoms. Different treatments of herpes zoster and its ocular complications have received much attention in the ophthalmic literature, owing to the increased frequency with which we are seeing the disease both in the younger immunocompromised patients and in the growing geriatric population. Our patient experienced successful resolution of his lesions with concomitant disappearance of pain while using acyclovir, prednisone, and cimetidine. These three medications have been the mainstay of therapy for the acute manifestations of ophthalmic zoster for the past several years. Oral acyclovir, in a prospective, randomized placebo- controlled trial, shortened the duration of viral shedding, resulted in more prompt resolution of signs and symptoms, and reduced the incidence and severity of secondary ocular inflammatory disease. It had its most significant effect if given within 72 hours after the onset of the skin rash (14). Patients presenting with acute herpes zoster ophthalmicus should probably be started on acyclovir, since it is the safest and most effective antiviral agent available for the disease; a dose of 800 mg five times a day is now recommended (15). J Clin Neuro-ophlhalmol, Vol. 13, No.4, 1993 Although topical acyclovir is not available in the United States, the 3% ophthalmic ointment has been compared with topical steroids in British studies (16,17). In a prospective randomized study comparing topical acyclovir to betamethasone, the acyclovir did result in slightly faster resolution of corneal disease, but, generally, the two were equally effective in the initial treatment of the disease (18). However, when the medications were discontinued after several months of treatment there was a significant recurrence of keratouveitis in the steroid-treated group but not in the acyclovir- treated group. The use of systemic steroids is still controversial (1,15). The rationale for their use is that they are felt to decrease the duration of the rash and the associated pain, in addition to reducing the incidence of postherpetic neuralgia. The rationale against their use is the exact opposite of the foregoing, that is, at best, they slightly reduce the duration of the lesions and the acute pain while having no effect upon the incidence or severity of postherpetic neuralgia. The possible benefits of this therapy must be weighed against the potentially serious systemic complications of steroids. This treatment modality should be considered only for immunocompetent patients, owing to the risk of disseminated herpes in the immunocompromised host. Steroids do, nonetheless, have an established role in the treatment of conditions such as the orbital apex syndrome and several scleritis (15). When given, steroids should be combined with acyclovir. Although the efficacy of cimetidine is also controversial, its side effect profile makes it a relatively safe drug to use. Some authors feel that it reduces pain and accelerates healing in the acute phase (18). It may exert its immunomodulatory effect via histamine (H2) receptors on supressor T-cells, and it may alter pain perception via an endorphinlike effect on the central nervous system. A random- HERPES ZOSTER OPHTHALMICUS 253 ized, prospective placebo-controlled study, however, demonstrated neither pain relief nor accelerated healing of lesions (19). Since antiviral therapy does not prevent or cure the pain of postherpetic neuralgia, several modes of therapy have been directed at this problem. Stellate ganglion blocks and other anesthetic/ neurosurgical procedures have met with limited success. Low doses of amitriptyline, up to 25-75 mg nightly, have been moderately helpful (15). Capsaicin cream, a substance P inhibitor, has been found to mollify the pain of both acute and postherpetic neuralgia. It has a specificity for nociceptive, type C nerve fibers without affecting sensations of touch, pressure, or vibration. It is applied topically four times a day (15). We have discussed the pathophysiology, anatomic correlates, and the treatment of herpes zoster ophthalmicus. To our knowledge this is the first fully documented report of herpes zoster ophthalmicus causing a Horner syndrome. REFERENCES 1. Karbassi M, Raizman MB, Schuman JS. Herpes zoster ophthalmicus. Surv Ophthalmol 1992;36:395-410. 2. Harding SP, Lipton JR, Wells JCD. Natural history of herpes zoster ophthalmicus: predictors of postherpetic neuralgia and ocular involvement. Br JOphthalmoI1987;71: 353--8. 3. Marsh RJ, Dulley B, Kelly V. External ocular motor palsies in ophthalmic zoster: a review. Br JOphthalmoI1977;61:67782. 4. Giles CL, Henderson JW. Homer's syndrome: an analysis of 216 cases. Am J Ophthalmol 1958;46:289-96. 5. Jarret WHo Homer's syndrome with geniculate zoster. Am J OphthalmoI1967;63:326--9. 6. Wimlararatna HSK, Capildeo R, Lee HY. Herpes zoster of second and third segments causing ipsilateral Horner's syndrome. Br Med J1987;294:1463. 7. Parkinson D. Bernard, Mitchell, Homer syndrome and others? Surg Neurol 1979;11:221-3. 8. Hartman B, Kremer I, Gutman I, Krakowski D, Kam J. Cavernous sinus infection manifested by Homer's syndrome and ipsilateral sixth nerve palsy. J Clin Neuro-ophthalmol 1987;7:223. 9. Stuph GG, Burde RM. Abducens nerve palsy and Horner's syndrome revisited. J Clin Neuro-ophthalmoI1988;8:13. 10. Parkinson D, Johnston J, Chaudlau A. Sympathetic connections of the fifth and sixth cranial nerves. Anat Rec 1978; 191:221. 11. Miller NR. Walsh and Hoyt's clinical neuro-ophthalmology, 4th Ed. Baltimore: Williams & Wilkins; 1985:425-8, 703--5, 1012-5. 12. Hedges TR III, Albert DM. The progression of the ocular abnormalities of herpes zoster. Opthalmology 1982;89:16577. 13. Liesang TJ. Biology and molecular aspects of herpes simplex and varicella-zoster virus infections. Ophthalmology 1992;99:781-99. 14. Cobo LM, Foulks GN, Liesegang TM, et aI. Oral acyvlovir in the therapy of acute herpes zoster ophthalmicus. Ophthalmology 1985;92:1574-83. 15. Liesegang TJ. Diagnosis and therapy of herpes zoster ophthalmicus. Ophthalmology 1991;98:1216--29. 16. McGill J. Topical acyclovir in herpes zoster ocular involvement. Br J Ophthalmol 1981;65:542-5. 17. McGill J, Chapman C. A comparison of topical acyclovir with steroids in the treatment of herpes keratouveitis. Br J OphthalmoI1983;67:746--50. 18. Van der Spuy S, Levy DW, Levin W. Cimetidine in the treatment of herpesvirus infections. 5 Afr Med J 1980;58: 112-16. 19. Levy DW, Banerjee AK, Glenny HP. Cimetidine in the treatment of herpes zoster. J R Coll Physicians Lond 1985;19: 96--8. JClin Neuro-ophthalmol, Vol. 13, No.4, 1993 |
