Journal of Neuro-Ophthalmology, September 2006, Volume 26, Issue 3

Orbital Apex Syndrome From Gnathostomiasis

A 16-year-old Thai girl presented with acute unilateral visual loss, proptosis, and ophthalmoparesis. CT demonstrated thickening and enhancement of orbital tissues including the orbital apex. A history of consumption of raw fish, together with the findings of cutaneous migratory swelling and eosinophilia, made the diagnosis of gnathostomiasis likely. Her serum was positive for Gnathostoma spinigerum using an immunoblotting technique. Parasites removed from the skin lesions revealed the typical head bulbs with 4 circumferential rows of hooklets and fine cuticular spines on their surface. Treatment with an antihelminthic and systemic corticosteroids led to resolution of orbital inflammation but left a persistent optic neuropathy marked by nerve fiber bundle visual field loss with normal visual acuity. Gnathostomiasis should be suspected in patients with an orbital apex syndrome who live or travel in an endemic area, have eaten raw fish, and develop a migratory skin rash.

ORIGINAL CONTRIBUTION Orbital Apex Syndrome From Gnathostomiasis Pisit Preechawat, MD, Pattama Wongwatthana, MD, Anuchit Poonyathalang, MD, and Araya Chusattayanond, PhD Abstract: A 16- year- old Thai girl presented with acute unilateral visual loss, proptosis, and ophthal-moparesis. CT demonstrated thickening and en­hancement of orbital tissues including the orbital apex. A history of consumption of raw fish, together with the findings of cutaneous migratory swelling and eosinophilia, made the diagnosis of gnathosto­miasis likely. Her serum was positive for Gnathos-toma spinigerum using an immunoblotting technique. Parasites removed from the skin lesions revealed the typical head bulbs with 4 circumferential rows of hooklets and fine cuticular spines on their surface. Treatment with an antihelminthic and systemic corticosteroids led to resolution of orbital inflamma­tion but left a persistent optic neuropathy marked by nerve fiber bundle visual field loss with normal visual acuity. Gnathostomiasis should be suspected in patients with an orbital apex syndrome who live or travel in an endemic area, have eaten raw fish, and develop a migratory skin rash. (/ Neuro- Ophthalmol 2006; 26: 184- 186) The orbital apex syndrome results from damage to the third, fourth, or sixth cranial nerves or to the ophthal­mic division of trigeminal nerve in association with optic nerve dysfunction. This syndrome includes the clinical findings of unilateral visual loss, proptosis, ptosis, and ophthalmoplegia. The syndrome may be caused by inflam­matory, infectious, neoplastic, traumatic, or vascular pro­cesses. Infectious diseases reported to cause this syndrome include bacteria, fungi, and spirochetes ( 1). Gnathostomiasis is an important food- borne parasitic disease ( 2). Humans are accidental hosts, acquiring infec­tion by eating third- stage larvae encapsulated in raw fresh­water fish. The disease manifests with migratory swelling or creeping eruption accompanied by visceral symptoms Departments of Ophthalmology ( PP, PW, AP) and Microbiology ( AC), Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. Address correspondence to Pisit Preechawat, MD, 904 Lincoln Court Avenue, Atlanta, GA 30329; E- mail: akepisit@ gmail. com related to larval migration. The parasite may migrate to the central nervous system and cause serious effects such as encephalomyelitis and meningitis with long- term neuro­logic sequelae, even death ( 3,4). Ocular involvement is rare but has been reported to include the eyelid, conjunctiva, cornea, anterior chamber, vitreous cavity, and retina ( 5). We report a rare case of a young girl with gnathostomiasis who presented with a progressive orbital apex syndrome, a phenomenon not previously published to our knowledge. CASE REPORT A 16- year- old girl presented with a 2- day history of pain, swelling, tearing, and minimal blurring of vision in the left eye. Visual acuity was 20/ 20 in the right eye and 20/ 25 in the left eye. There was moderate erythematous eyelid edema with conjunctival hyperemia. Pupillary reac­tions and ocular motility were normal. A diagnosis of preseptal cellulitis was made and oral dicloxacillin was prescribed. Twelve hours later, the patient returned to the hospital reporting progressive painful eyelid swelling in her left eye. She now had left proptosis and chemosis and diminished abduction of the left eye. Visual acuity had fallen to 20/ 200 in the left eye with a relative afferent pupillary defect. Ante­rior segment and funduscopic examinations were normal in both eyes. The patient was hospitalized with a provisional diagnosis of left orbital celluUtis and started on intravenous vancomycin, ceftriaxone, and metronidazole. Twelve hours after admission, visual acuity in the left eye had decreased to light perception associated with increased proptosis and chemosis. In addition, left eye ductions had diminished to less than 10% in all directions of gaze. Mydriasis and diminished corneal sensation in the left eye were also noted. The remainder of the patient's neuro- ophthalmologic examination was unremarkable. Pyrexia was absent. Laboratory results included hemo­globin 12.3 g/ dL, white blood count 16,200/ mm3 ( 49% polymorphonuclear cells, 14% lymphocytes, 31% eosino­phils, and 6% monocytes), platelets 276,000/ mm3, and normal erythrocyte sedimentation rate. CT of the orbits and cavernous sinuses demonstrated diffuse thickening and enhancement along the wall of the left globe, optic nerve, and extraocular muscles ( Fig. 1 A). Enhancing lesions at the 184 J Neuro- Ophthalmol, Vol. 26, No. 3, 2006 Gnathostomiasis J Neuro- Ophthalmol, Vol. 26, No. 3, 2006 FIG. 1. A. Postcontrast axial CT at presentation shows left proptosis, an enlarged left optic nerve, and an enhancing mass in the left orbital apex. B. Postcontrast fat- suppressed T1 axial MRI 1 week after starting therapy shows improvement in proptosis and less evidence of orbital inflammation. left orbital apex and superior orbital fissure were also seen. The paranasal sinuses were normal. There was no evidence of cavernous sinus thrombosis. The patient recalled an additional history of migra­tory erythematous swelling in her ankle, waist, back, and neck approximately 1 month earlier. A differential diagno­sis of parasitic larva migrans was considered. Intravenous dexamethasone at a dosage of 5 mg four times per day and 400 mg oral albendazole twice per day were initiated. Cerebrospinal fluid examination revealed no cells, normal protein and sugar, and negative staining for organisms. After 24 hours of corticosteroid therapy, the patient showed remarkable improvement with decreased lid swell­ing, chemosis, and proptosis, and resolution of pain. Visual acuity had improved to hand movements. During the next several days, the patient showed further improvement of visual acuity and ocular motility. Hemoculrure and cerebro­spinal fluid culture for bacteria was negative, but serum was positive for Gnathostoma spinigerum using an immuno-blotting technique ( 24- kDa diagnostic band). Intravenous antibiotic and dexamethasone were discontinued after 3 days and the patient was treated with 1 mg/ kg oral prednis­olone per day in addition to albendazole. By 1 week after treatment, the patient had resolution of proptosis and ocular motility was significantly improved in all directions except for a mild abduction deficit. Visual acuity had improved to 20/ 50; kinetic perimetry revealed an inferior altirudinal defect. MRI showed marked improve­ment of periorbital and orbital inflammation ( Fig. IB). The patient was discharged on oral prednisolone and albenda­zole for 2 weeks. One week later, visual acuity was 20/ 40; there was minimal subconjunctival hemorrhage, resolution of conjunc­tival edema, full ocular motility, and no proptosis. Creeping eruptions were now found on her left leg and right shoulder. Parasites were removed from the lesions and identified microscopically as third- stage larvae of the Gnathostoma species. Microscopic study of the parasites revealed a typical head bulb with 4 circumferential rows of hooklets and fine cuticular spines on its surface ( Fig. 2). Visual acuity had recovered to 20/ 20 by 6 months. Visual field examination showed a persistent inferior arcuate- altirudinal defect that corresponded to supero-temporal sectoral pallor of the left optic disc ( Fig. 3). Over 2 years of follow- up, she has had no further ocular or neurologic symptoms. FIG. 2. Microphotograph of the parasite under a coverslip in wet preparation shows the head bulb with 4 rows of hooklets ( short arrow) and multiple cuticular spines on the body ( long arrow). These features indicate a third- stage larva of the Gnathostoma species. 185 J Neuro- Ophthalmol, Vol. 26, No. 3, 2006 Preechawat et al FIG. 3. Kinetic perimetry of left eye ( left) shows an inferonasal arcuate-altitudinal visual field defect that corresponds to superotemporal sec­toral pallor of the left optic disc ( right). DISCUSSION Gnathostomiasis, caused by Gnathostoma spinigerum, is commonly seen in Thailand and many Asian countries. The clinical symptoms are related to the mechanical disruption caused by third- stage larval migration and the inflammatory reaction provoked by this parasite. Any organ system can be involved, but the most common manifes­tation of infection is localized, intermittent migratory swelling in skin and subcutaneous tissues. Lid swelling and intraocular parasites are the two most common ocular manifestations ( 6). The parasite may be found in either the anterior or posterior ocular segment and can cause uveitis, secondary glaucoma, and hemorrhage in the vitreous, ret­ina, or choroid ( 5). The larvae may migrate along the optic nerve before entering the eye, causing orbital inflammation. Sen et al ( 7) reported a case of orbital inflammation mimicking orbital cellulitis followed by vitreoretinal hem­orrhage associated with intraocular gnathostomiasis. Ocular motor nerve palsy, pupillary disorders, visual field defects, and optic neuropathy can be seen but usually develop in pa­tients with central nervous system involvement, including meningitis, encephalitis, and subarachnoid or intracranial hemorrhage ( 3,4). The key to diagnosis of gnathostomiasis is recogni­tion of the highly suggestive clinical history. Recurrent migratory swelling and eosinophilia in a patient who is living or has traveled in an endemic area make the diagno­sis likely. Many tests are available for the detection of Gnathostoma antigens and anti- Gnathostoma antibodies ( 8). The serologic test using the immunoblotting technique with a polypeptide marker weight of 24 kDa of Gnathostoma spinigerum has nearly 100% specificity ( 9,10). Our case of gnathostomiasis was confirmed with this test and by recovery of the migrating larvae from the patient's skin lesions. Albendazone and ivermectin have been used to treat subcutaneous gnathostomiasis but no effective drugs are yet available for the treatment of intracranial or intraocular involvement. Immediate treatment with systemic cortico­steroids in our patient improved the condition, resulting in significant recovery. REFERENCES 1. Yeh S, Foroozan R. Orbital apex syndrome. Curr Opin Ophthalmol 2004; 15: 490- 8. 2. Magana M, Messina M, Bustamante F, et al. Gnathostomiasis: clinicopathologic study. Am JDermatopathol 2004; 26: 91- 5. 3. Boongird P, Phuapradit P, Siridej N, et al. Neurological manifes­tations of gnathostomiasis. J Neurol Set 1977; 31: 279- 91. 4. Punyagupta S, Bunnag T, Juttijudata P. Eosinophilic meningitis in Thailand. Clinical and epidemiological characteristic of 162 patients with myeloencephalitis probably caused by Gnathostoma spinige­rum. J Neurol Sci 1990; 96: 241- 56. 5. Biswas J, Gopal L, Sharma T, et al. Intraocular Gnathostoma spinigerum: clinicopathologic study of two cases with review of literature. Retina 1994; 14: 438^ 14. 6. Teekhasaenee C, Ritch R, Kanchanaranya C. Ocular parasitic infection in Thailand. Rev Infect Dis 1986; 8: 350- 6. 7. Sen K, Ghose N. Ocular gnathostomiasis. Br J Ophthalmol 1945; 29: 618- 26. 8. Tapchaisri P, Nopparatana C, Chaicumpa W, et al. Specific antigen of Gnathostoma spinigerum for immunodiagnosis of human gnathos­tomiasis. IntJParsitol 1991; 21: 315- 9. 9. Tuntipopipat S, Chawengkirttikul R, Sirisinha S. A simplified method for the fractionation of Gnathostoma- specific antigens for serodiag-nosis of human gnathostomiasis. J Helminthol 1993; 67: 297- 304. 10. Nopparatana C, Setasuban P, Chaicumpa W, et al. Purification of Gnathostoma spinigerum specific antigen and immunodiagnosis of human gnathostomiasis. Tnt J Parasitol 1991; 21: 677- 87. 186 © 2006 Lippincott Williams & Wilkins [CLorbitalinfections]