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Show Journal of Clinical Neuro- opl1tlwlmo[ ogy 12( 4): 245- 249, 1992. © 1992 Raven Press, Ltd., New York Indolent Orbital Apex Syndrome Caused by Occult Mucormycosis David P. Dooley, M. D., F. A. C. P., Donald A. Hollsten, M. D., Steven R. Grimes, M. D., and Jesse Moss, Jr., M. D. The chronic or indolent presentation of rhino- orbital mucormycosis, as defined by the presence of symptoms for more than 1 month before diagnosis, is extremely unusual. A 45- year- old man with stable diabetes presented with a right orbital apex syndrome and minimal ethmoid and sphenoid sinusitis. Progression was indolent, and the diagnosis was not made until 7 weeks after admission, when a third biopsy was prompted by new cavernous sinus and carotid artery thromboses. Mucormycosis was found. The patient improved on amphotericin B ( 2 g) and strict blood glucose control. A remarkable aberrant regeneration of the right oculomotor nerve was seen following treatment. He remains free of active disease 4 years later. Orbital symptoms in well- controlled diabetics, which may even remain stable for weeks and lack direct signs of tissue invasion, should raise the suspicion of mucormycosiS. From the Departments of Medicine ( D. P. D.), Ophthalmology ( D. A. H., S. R. G.), and Otolaryngology ( J. M.), Brooke Army Medical Center, Fort Sam Houston, Texas, U. S. A. Dr. Jesse Moss Jr. is now at the Toepperwein Medical Center, San Antonio, TX 78233. The opinions or assertions herein are the private views of the authors and are not to be construed as reflecting the views of the Department of the Army or the Department of Defense. Address correspondence and reprint requests to Dr. David P. Dooley, U. S. Army Medical Corps SGHMMI, Wilford Han Medical Center, Lackland AFB, IX 78236, U. S. A. 245 The dramatic presentation of the patient with rhino- orbital mucormycosis generally allows a rapid diagnosis to be made. When symptoms of pain, local tissue invasion, and sudden craniofacial neurological deficits progress over a period of hours to days in a poorly controlled diabetic, and are associated with compatible physical and radiographic findings, the diagnosis is almost certain ( 1- 3). Carotid artery involvement is usually a preterminal event ( 4,5). The very rare patient, however, presents with a relatively benign, indolent disease ( 4,6,7). We recently treated a patient who developed an indolent orbital apex syndrome ( 8) caused by mucormycosis that progressed over 7 weeks before the diagnosis was made. Despite eventual cavernous sinus, carotid artery, and ophthalmic artery thromboses, he was eventually cured by medical therapy alone; ultimately, aberrant regeneration of the right third cranial nerve occurred. CASE REPORT A 45- year- old man was admitted with a 4- day history of right retrobulbar pain, decreasing visual acuity in the right eye, ptosis of the right upper lid, diplopia, and 2 days of nausea and vomiting. Physical examination revealed an afebrile, obese man with a nontoxic appearance and slight ptosis and proptosis on the right. The visual acuity was 20/ 50 in the right eye and 20/ 20 in the left eye. A slight deficit of downgaze and trace conjunctival injection were apparent in the right eye. The pupils were 4 mm bilaterally; confrontational visual fields, intraocular pressures, orbital resilience, and the rest of the eye examination were normal in both eyes. The remainder of the physical examination was unremarkable. Diabetes had been diagnosed 18 months previously, and blood sugars had uniformly run below 150 mgldl on oral hypoglycemic agents. 246 D. P. DOOLEY ET AL. The white cell count was 9,000/ mm3 , and never exceeded II, 000/ mm3 during the hospital stay. The random blood sugar was 319 mg/ dl, and the creatinine and BUN were normal. He was never acidotic. A computed tomographic ( CT) scan revealed only slight exophthalmos on the right and slight mucosal thickening in the right sphenoid and ethmoid sinuses, which magnetic resonance imaging ( MRI) confirmed. A carotid arteriogram and an I133- tagged white cell scan were normal. A preliminary diagnosis of an orbital inflammatory syndrome was made, and steroids ( dexamethasone 30 mg i. v., followed by prednisone 100 mg a day orally) were started immediately after admission. Insulin was required to maintain tight blood sugar control once the steroids were added. Marked but transient improvement was followed by rapid deterioration on the third hospital day. An examination revealed paresis of all branches of the third cranial nerve and a right eye visual acuity of 20/ 25. Steroids were discontinued. A lumbar puncture was normal except for a protein of 0.65 gIL ( 65 mg/ dl). Over the ensuing 6 weeks, a complete right orbital apex syndrome developed ( complete involve-ment of cranial nerves II, III, IV, VI, and V. I.). He continually felt well, except for occasional orbital headache, and remained afebrile. An initial sphenoidotomy, performed on the 10th hospital day, and follow- up sphenoidotomy, performed 3 weeks after admission when the maxillary branch of the right trigeminal nerve became involved, were not diagnostic, with all appropriate stains and cultures negative. A routine follow- up MRl performed in the sixth hospital week ( Fig. 1) showed a suggestion of right internal carotid artery thrombosis, the presence of a soft tissue fullness in the area of the right superior orbital fissure, and a thrombosed cavernous sinus. Angiography revealed occlusion of the right internal carotid artery from the carotid bulb to the circle of Willis, with filling of the anterior and middle cerebral arteries from the left internal carotid. Computed tomography revealed new bony destruction of the posterior lateral wall of the right sphenoid sinus. A third sphenoidotomy found the lateral wall of the sinus to be destroyed, with cheesy, necrotic tissue extending into the adjacent cavernous sinus. Cultures were negative, but wide ( 20~ 0 IJ.. m) hyphaI elements were seen on all FIG. 1. ( A) Transverse magnetic resonance image demonstrating soft tissue fullness In area of nght superior orbital fissure and cavernous sinus ( black arrow). Note loss ~ f surrounding flow Signal [ compared to left cavernous sinus ( arrowhead » ). indicating nght cavernous SinUS thrombosis. ( B) Coronal images suggest loss of right internal carotrd flow [ black arrows; compared to intact flow signal in left internal carotid ( arrowheads)]; nght Internal carotid thrombosis was confirmed by arteriography. I Cl111 NClirv- opfllhafm( i!, \' 0/. 12, Nl), 4, 1992 INDOLENT MUCORMYCOSIS AND ORBITAL APEX SYNDROME 247 pathological sections ( Fig. 2), diagnostic of invasive tissue disease caused by a member of the Mucoraceae family. The patient refused further debridement, and was treated with a 6- week course of amphotericin B ( 2 g). The headache resolved, no symptomatic or radiographic progression occurred, and by the end of therapy there was improved function of the fourth and VI cranial nerves. He continued to improve, and by 18 months later a CT scan confirmed regeneration of bone in the lateral wall of the sphenoid sinus and the absence of soft tissue involvement. By this time a near- total return of sixth nerve function, an incomplete regeneration of VI, and aberrant regeneration of the third nerve on the right were apparent ( Fig. 3). Isolated sectors of the pupillary sphincter would constrict with attempted change in gaze position; a slight elevation of the upper lid on attempted downgaze and a more significant elevation of the upper lid on attempted left gaze occurred; and a slight depression of the right eye on attempted upgaze was seen. His condition remains stable 4 years after presentation. COMMENT Classically, rhinocerebral mucormycosis presents as a subacute ( progressing over days) to ful-minant ( over hours), invasive, necrotizing process which begins in the nasal mucosa, progresses through the sinuses to the orbit, and may eventually invade or infarct the brain. Most patients are diabetic, in poor blood sugar control, and frankly acidotic ( 1- 3). Although the disease is not uniformly fatal as previously described ( 3), the development of carotid artery occlusion indicates a miserable prognosis ( 5). In the century since the first report of rhinocerebral mucormycosis ( 9), only three patients have been reported with indolent presentations ( symptoms for more than 1 month before diagnosis) ( 4,6,7). Between 6 weeks and 6 months elapsed before the correct diagnosis was made in these patients, although each patient possessed additional features that suggested mucormycosis ( diabetic ketoacidosis in two, and foul nasal discharge with retinal artery occlusion in the other). Our patient presented and lingered with no such suggestive findings; neither did he demonstrate the obvious orbital CT findings which most patients will have on or shortly after presentation ( 10). An additional extremely unusual feature of this presentation of mucormycosis was the development of aberrant regeneration of the right oculomotor nerve after what typically is an irreversible ischemic insult. A vasotropic infection, mucormycosis invades arterial walls, resulting in thrombo- FIG. 2. Branching, nonseptate, wide (> 20 IJom) hyphal elements of mucormycosis ( arrow) in necrotic debris from sphenoid wall and cavernous sinus biopsy. ( Hematoxylin and eosin, x 1000.) I Clin NeuTo- aphtha/ mol. Vol. 12, No. 4, 1992 248 A D. P. DOOLEY ET AL. FIG. 3. lA) t-> atlent In primary gaze. Note ptosis 00 and slight hypotropia of right globe. ( B) Attempted upgaze. Note adduction of right globe, indicating medial rectus contraction. ( C) Attempted left gaze. Note aberrant levator activity in the right upper lid, slightly raising lid. ( D) Attempted downgaze. Note slight elevation of right upper lid and adduction of right globe. INDOLENT MUCORMYCOSIS AND ORBITAL APEX SYNDROME 249 sis, necrosis, and infarction of those areas supplied by involved vessels. Propagation of vascular invasion into the internal carotid artery, as seen in our patient, is an extremely ominous sign ( 5). It was a surprise, then, to observe the extent of aberrant regeneration of the oculomotor nerve in this case. This phenomenon is generally seen following less severe mechanical insults, which, although initially causing axonal disruption, will subsequently allow regrowth from residual neurons into intact but incorrect myelin sheaths to ultimately innervate incorrect structures. Nevertheless, medical therapy resulted not only in halting the progression of disease in our patient, but sufficiently eradicated the infection such that a remarkable degree of aberrant regeneration occurred. Although Ferstenfeld's case suggests that mucormycosis in the well- controlled diabetic may remain quiescent for years ( 7), we believe that our patient's prolonged disease- free survival together with the aberrant regeneration portend an excellent prognosis for a complete cure of the disease. We are unable to explain with certainty the reason for our patient's indolent presentation, eventual survival despite delayed therapy, and even significant neuronal regeneration. It is possible that a critical mass of devascularized tissue, in which the fungus could escape host defenses and proliferate, was never reached. Alternatively, the absence of the ketoacidotic milieu present in most cases of rhino- orbital mucormycosis, known to enhance the proliferation of this fungus in vitro ( 10), may have inhibited disease progression in our patient, or he may have differed from other patients in the amount or efficacy of innate serum fungicidal activity ( 12,13). In summary, a diabetic man presented with an orbital apex syndrome and internal carotid artery thrombosis caused by mucormycosis occurring in a remarkably indolent fashion. Aberrant regeneration of the right third cranial nerve was seen following antifungal therapy, suggesting that even the severe neurophthalmologic events that characterize this disease may be, to an extent, reversible. Acknowledgments: The authors wish to thank Dr. e. K. McAllister for reviewing the manuscript, Dr. Bruce Brown for preparation of Figure 2, and Mr. David Amthauer and Mrs. Bettye J. Hairston for editorial assistance. REFERENCES 1. Benbow EW, Stoddart RW. Systemic zygomycosis. Postgrad Med J1986; 62: 982. 2. Rangel- Guerra R, Martinez HR, Saenz C. Mucormycosis: report of 11 cases. Arch Neural 1985; 42: 578-- 81. 3. Parfrey NA. Improved diagnosis and prognosis of mucormycosis. Medicine 1986; 65: 113- 23. 4. Bentwich Z, Rosen A. Ganor S, Herman G. Chronic rhinocerebral mucormycosis ( phycomycosis) with occlusion of left internal carotid artery. Isr JMed Sci 1968; 4: 977- 81. 5. Anaissie IF, Shikhani AH. 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A mechanism of susceptibility to mucormycosis in diabetic ketoacidosis: transferrin and iron availability. Diabetes 1982; 31: 1109- 14. 13. Artis WM, Patrusky E, Rastinefad F, Duncan RL. Fungistatic mechanism of human transferrin for Rhizopus orywe and Trichophyton mentagrophytes: alternative to simple iron deprivation. Infect Immun 1983; 41: 1269- 78. I Clin Neuro- ophthalmoI. Vol. 12, No. 4, 1992 [CLcavernoussinusthrombosis] [CLorbitalinfections] |
