Journal of Neuro-Ophthalmology, June 1984, Volume 4, Issue 2

Internal ophthalmoplegia resulting from acute orbital phycomycosis.

Phycomycosis is an opportunistic infection occurring in immunocompromised hosts. It is the most acutely fatal fungal disease known. Therefore, early recognition and treatment are essential. Ocular and orbital involvement is part of a rhino-orbital-cerebral form of the disease. The orbital apex syndrome is the hallmark orbital involvement. A case of phycomycosis with internal ophthalmoplegia alone is reported. The internal ophthalmoplegia is probably secondary to involvement at the apex of the orbit, although not sufficiently diffuse to result in the complete orbital apex syndrome.

f. Clin. Neuro-ophthalmol. 4: 105-108, 1984. Internal Ophthalmoplegia Resulting from Acute Orbital Phycomycosis GEORGE MARK SCHWARTZE, M.D. GARY R. KILGO, M.D. e. STEPHEN FORD, M.D. Abstract Phycomycosis is an opportunistic infection occur­ring in immunocompromised hosts. It is the most acutely fatal fungal disease known. Therefore, early recognition and treatment are essential. Ocu­lar and orbital involvement is part of a rhino-or­bital- cerebral form of the disease. The orbital apex syndrome is the hallmark orbital involvement. A case of phycomycosis with internal ophthalmople­gia alone is reported. The internal ophthalmoplegia is probably secondary to involvement at the apex of the orbit, although not sufficiently diffuse to result in the complete orbital apex syndrome. Phycomycosis is an opportunistic fungal infec­tion occurring typically in immunocompromised hosts. Acute orbital phycomycosis is part of a rhino-orbital-cerebral form of the infection. I Other reported forms are pulmonary, gastro­intestinal, disseminated, medullary, cutaneous, brain abscess, and chronic meningitis. 2 - 5 We de­scribe a patient in whom pupillary involvement was an early sign of acute orbital infection. The fulminant nature of this infection coupled with its delayed recognition is partly responsible for poor survival in spite of vigorous therapy.6 Case Report A 19-year-old diabetic woman presented com­atose in ketoacidosis. General exam revealed Kussmaul respirations, tachycardia, and hypo­thermia. Neurologically, the pupils were 6 mm bilaterally and reacted directly and consensually to light. Oculocephalics were intact and the fun- From the Department of Neurology, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina. June 1984 dus was normal. Deep tendon reflexes were dif­fusely hypoactive. There were no pathologic re­flexes and the neck was supple. Laboratory values were as follows: glucose 692 mg%, sodium 136 meg/liter, potassium 1.5 meq/liter, chloride 114 meq/liter, carbon dioxide 6.0 meg/liter, hemo­globin 14.7 g, hematocrit 43%, and leukocytes 21,100 cells/mm3 with a leftward shift. The uri­nalysis showed glycosuria and ketonuria. Treat­ment was started with sodium bicarbonate, nor­mal saline, potassium, and low-dose insulin in­fusion. After 8-10 hours, the serum glucose was decreased to 250 mg%, serum electrolytes had corrected, and the acidemia was almost resolved. The patient remained stuporous, became hyper­thermic, and manifested a stiff neck. A comput­erized cranial tomography with infusion was nor­mal (including sinuses). Lumbar puncture showed an opening pressure at 280 mm, glucose 263 mg%, protein 107 mg%, a leukocytosis of 852 cells/mm3 with 364 neutrophils, and 488 lymphocytes. All stains, cultures, and antigenic assays were negative. On the second hospital day, the mental status improved to the point of responding to simple commands and answering some questions. That evening the right pupil became dilated and fixed to light. The left pupil continued to react directly and consensually to light. The extraocular move­ments remained normal. A second computerized cranial tomography was normal. The next day the mental status worsened. The patient could still be aroused and when awake there was right ptosis as well as a dilated and fixed right pupil. In addition periorbital edema was noted. A pu­rulosanguinous nasal discharge appeared on the fourth hospital day. Sinus tomography revealed minimal mucous membrane thickening in the maxillary sinuses. Nasal cultures were obtained. On the fifth hospital day, a palatal lesion was noted. Biopsy revealed nonseptate branching hy­phae. The patient was started on Amphotericin B and improved rapidly. The nasal cultures grew 105 Internal Ophthalmoplegia phycomycosis. She received 1.5 g of Amphoteri­cin B over the next 6 weeks and was discharged. Follow-up 3112 years later reveals a 21f2-3-mm ptosis of the right upper lid with excellent levator function (15 mm). Palpebral fissures were about 8 mm on the right and 10112-11 mm on the left. Extraocular movements are normal and the right pupil remains dilated at 6 mm and fixed to light. Comment The prolonged altered mental status, fever, meningismus, and marked cerebrospinal fluid leukocytosis all implied something more than di­abetic ketoacidosis coma. The first clue was on day 2, a unilateral dilated and fixed pupil. The differential diagnosis to be considered included innoculation with a mydriatic or cycloplegic agent, Hutchinson pupil, Adie's tonic pupil, and internal ophthalmoplegia. Because of the occur­rence of the dilated and fixed pupil while under surveillance in the intensive care unit, innocula­tion with a mydriatic or cycloplegic agent was considered unlikely. Herniation was strongly con­sidered at first because of the possibility of cere­bral edema which can complicate the treatment of diabetic ketoacidosis. The second computerized cranial tomography was normal, however. An Adie's tonic pupil was considered since the pa­tient was a young female with hypoactive deep tendon reflexes. Internal ophthalmoplegia was also considered. The periorbital edema with prop­tosis and the purulosanquinous nasal discharge suggested phycomycosis; therefore, cultures on Sabouraud agar were done. The biopsy of a pal­atal lesion revealed the nonseptate hyphae char­acteristic of phycomycosis. Discussion Phycomycosis is the most acutely fatal fungal disease in man. 7 Typically, the patient presents in diabetic ketoacidosis coma. After treatment there may be clearing of the sensorium and in a few days the patient will develop rhinitis or sinusitis and rapidly become unresponsive. Another com­mon scenario is the diabetic in good control who presents with complaints of sinusitis, rhinitis, or facial pain. The patient may become obtunded within hours. H Other states which cause an aci­dosis such as dehydration or renal disease have also been associated with phycomycosis. Leuke­mias, lymphomas, and other nonsolid neoplasms also predispose to opportunistic infections such as phycomycosis. ~ There is also belief that anti­biotics, steroids, and antineoplastic agents in­crease the risk of contracting phycomycosis.H Whichever predisposing risks are present, the clinical triad of proptosis (with orbital cellulitis), acidosis (especially in the diabetic), and total ophthalmoplegia in the proper setti~g i~ ~aid t~ be sufficient to diagnose phycomycosls chmcally. Of the several clinical variations of acute phy­comycosis, ocular manifestations a.re ~een i~ th~se who develop a fulminant mycotic mfectIon in­volving the nose, paranasal sinuses, orbit, and central nervous system. The nose is the portal of entry. The infection spreads, if con?itions are adequate, directly to the paranasal Sinuses and through the cribriform plate into t~e .leptomen­inges and the frontal lobes. The orbit IS Involved by spread from the sinuses. 1 Therefore, it is useful to distinguish three developmental stages and turn attention initially to the nose and sinuses. Characteristically, there is a purulosanginous ex­udate and an unpleasant odor. There is often facial swelling and tenderness over affected sin­uses. Intranasal exam may reveal necrotic turbi­nates and a gray-black discoloration resembling dried blood. When this gray-black discoloration is removed, one will find that this is an area of gangrene. Ischemic necrosis and perforation can involve the bone and cartilage of the nose and palate.H The hallmark of orbital involvement is the or­bital apex syndrome. This includes visual loss, internal and external ophthalmoplegia, ptosis, corneal anesthesia and anesthesia, and anhidrosis over the first and occasionally the second trigem­inal nerve distribution on that side. 1 The fundus­copic exam is initially normal, but later there is usually some venous engorgement and often manifestations of central retinal artery or vein occlusion.H Orbital cellulitis may be accompanied by infarction of the lids and orbital contents.8 From the orbit the infection often spreads poste­riorly to invade the internal carotid artery, basal meninges, pons, medulla, and cerebellum.! For a definitive diagnosis of the disease, the combination of a positive culture and microscopic evidence of phycomycosis is needed.8 All exudate and biopsy material should be cultured on Sa­bouraud's media. Because the organism is a fre­quent laboratory contaminant, a positive culture alone does not prove the diagnosis. 1 A biopsy is examined with hematoxylin and eosin, Schiff's periodic acid, or methenamine silver stains for nonseptate branching hyphae. The tissue changes are necrosis, polymorphonuclear leukocyte infil­tration, and colonization of the micro-organisms. The tissue necrosis is due to both local suppura­tion caused by the fungus, but mainly infarction caused by vascular thrombosis.8 One of the main characteristics of phycomycosis is their tendency to invade blood vessels. They destroy the elastic tissue of the vessels and are able to proliferate in the lumen where they produce fungoid thrombi.2 Journal of Clinical Neuro-ophthalmology Sites of common occlusion are the internal carotid artery, ophthalmic artery, ciliary artery, and the cavernous sinus.1.B· 9 Neuro-anatomic Considerations The pupillary abnormalities of dilatation and nonreactivity to light in phycomycosis are due to sympathetic and parasympathetic involvement.' The location of this involvement is most likely at the orbital apex. Parasympathetic innervation to the eye is supplied via the third cranial nerve. The third cranial nerve enters the orbit through the lower part of the superior orbital fissure it subdivides into the a superior branch and an inferior branch. The inferior branch gives off short twigs to the inferior and medial rectus mus­cles and a longer twig to the inferior oblique muscle. From this longer twig, a short, thick di­vision containing parasympathetic fibers passes to the lower part of the ciliary ganRlion which is situated near the apex of the orbit. 0 Postsynaptic neurons originating in the ciliary ganglion supply the sphincter of the pupil and the ciliary body via the short ciliary nerves. II Sympathetic innervation of the eye travels with the third and fifth cranial nerves. Along the seg­ment of the internal carotid artery between the carotid canal and the anterior clinoid apophysis the ocular sympathetic innervation leaves the internal carotid plexus at various levels. The fibers traveling with the ophthalmic division of V ini­tially have a retrograde course, but then turn forward and join the medial border of the Gas­serian ganglion and then follow the ophthalmic nerve and its nasociliary branch. 12 The nasociliary nerve communicates with the ciliary ganglion; also it gives off the long ciliary nerve. IO There are also filaments from the internal carotid plexus which travel with the third cranial nerve which arise from the cavernous sympathetic plexus. They travel to the ciliary ganglion with parasym­pathetic third nerve fibers, but they do not syn­apse there. They enter the globe by way of the short ciliary nerves. I I Involvement at the ciliary ganglion, therefore, affects both sympathetic and parasympathetic fi­bers. Moreover, sympathetic fibers other than pupillary fibers traverse or are near the ciliary ganglion at the orbital apex. In the present case, the internal ophthalmoplegia and ptosis probably represent interruption of sympathetic and para­sympathetic fibers at or near the ciliary ganglion near the orbital apex. In an earlier review of 34 cases, there were eight cases which manifested internal ophthalmoplegia without external ophthalmoplegia. I 3 Some of these cases do report orbital and globe pathologx at autopsy, but do not mention specific detail. 4-19 June 1984 Schwartze, Kilgo, Ford Because of the fulminant and frequently fatal results of this infection, early diagnosis and treat­ment must be emphasized. The pupillary findings in the present case were early signs of phyco­mycosis and could be considered a forme fruste of the more commonly seen orbital apex syn­drome. References 1. Gass, ].D.M.: Ocular manifestations of acute mu­cormycosis. Arch. Ophthamol. 65: 226-237, 1961. 2. Dhermy, P.: Phycomycosis (mucormycosis). In The Handbook of Clinical Neurology, Vol. 27, P.J. Vinken, G.W. Bruyn, and H.L. Klawans, Eds. North Hol­land Publ. Co., Amsterdam, 1978, pp. 541-555. 3. Edwards, J.E.: Clinical aspects of mucormycosis. [pp. 98-99 in Lehrer KI. (moderator): Mucormy­cosis.] Ann. Intem. Med. 93 (part 1): 93-108,1980. 4. Jones, P.C., Gilman, KM., Medeiros, AA, et al.: Focal intracranial mucormycosis presenting as chronic meningitis. f.A.M.A. 246: 2063-2064, 1981. 5. Weber, P.A, Makley, T.A, and Werling, K.: Cer­ebrorhino- orbital phycomycosis: A case report. AllIZ. Ophthalmol. 12: 459-463, 1980. 6. Pillsbury, H.C., and Fischer, N.D.: Rhinocerebral mucormycosis. Arch. Otolaryngol. 103: 600-604, 1977. 7. Abramson, E., Wilson, D., and Arky, KA: Rhino­cerebral phycomycosis in association with diabetic ketoacidosis. Ann. Intern. Med. 66: 735-742, 1967. 8. Schwartz, ].N., Donnelly, E.H., and Klintworth, G.K.: Ocular and orbital phycomycosis. Sun>. Ophthaill/oi. 22: 3-28,1977. 9. Walsh, F.B., and Hoyt, W.E.: Clinical Neuro-oph­thaill/ olo~y, Vol. 2, (3rd ed.). Williams and Wilkins Co., Baltimore, 1969, pp. 1486-1490. 10. Warwick, R., and Williams, P.L.: GraIl's Anatoml/, (35th Brit. ed.). W.B. Saunders Co., Philadelphia, 1973,pp. 999-1000; 1002-1004. 11. Burde, R.M.: Clinician's guide to the pupil. Int. Ophthalmol. Clill. 17(1): 139-155, 1977. 12. Toussaint, D.: Raeders syndrome. In The Handbook of Clinical Neurology, Vol. 5, P.]. Vinken and C.W. Bruyn, Eds. North Holland Pub!. Co., Amsterdam, 1968, pp. 334-335. 13. Ferry, AP.: Cerebral mucormycosis (phycomy­cosis). Ocular findings and review of the literature. Sum Ophthalmol. 6: 1-24, 1961. 14. Smith, H.W., and Kirchner, ].A: Cerebral mucor­mycosis: A report of three cases. Arch. Otolaryngol. 68: 715-726,1958. 15. Dolman, c.L.A., and Herd, ].A.: Acute pancreatitis in pregnancy complicated by renal cortical necrosis and cerebral mucormycosis. Cal1. Med. Assoc. f. 81: 852-856,1959. 16. Gregory, ].E., Golden, A., and Haymaker, W.: Mu­cormycosis of the central nervous system. A report of three cases. Bull. Johns Hopkins Hosp. 73: 405­419,1943. 107 Internal Ophthalmoplegia 17. Bauer, H., Ajello, L., Adams, E., et al.: Cerebral mucormycosis: Pathogenesis of the disease. De­scription of the fungus, rhizopus oryzae, isolated from a fatal case. Am. f. Med. 18: 822-831, 1955. 18. Smith, M.E., Burnham, O.K., and Black, M.B.: Ce­rebral mucormycosis. Report of a case. Arch. Pathol. 6~ 468-473, 1958. 19. LeCompte, P.M., and Meissner, W.A.: Mucormy- 108 cosis of the central nervous system associated with hemochromatosis. Am. f. Pathol. 23: 673-677, 1947. Write for reprints to: George M. Schwartze, M.D., Department of Neurology, Bowman Gray Medical School, 300 South Hawthorne Road, Winston-Salem, North Carolina 27103. Journal of Clinical Neuro-ophthalmology [CLorbitalinfections]