Neuroparalytic Keratopathy As the First Sign of a Cerebral Meningioma

NEUROPARALYTIC KERATOPATHY AS THE FIRST SIGN OF A CEREBRAL MENINGIOMA

VANTIEGHEM G.*, MAUDGAL P.C.*

ABSTRACT RÉSUMÉ We report a case of a cavernous sinus meningioma Nous présentons une patiente avec une kératite neu- in a young woman presenting with a neuroparalytic roparalytique comme premier signe d’un méningio- corneal ulcer as the only sign of the tumour. Clinical me cérébral. Nous avons constaté un ulcère cor- ophthalmic examination revealed a trophic corneal néen à l’oeil gauche, une cornée insensible et la per- ulcer in the left eye of the patient accompanied by te de la sensibilité au contact et à la douleur dans corneal anaesthesia and loss of sensation to touch les dermatomes du nerf ophtalmique et du nerf maxil- and pain stimuli in the ipsilateral dermatomes sup- laire. L’examen neurologique et l’IRM ont montré un plied by the ophthalmic and maxillary divisions of méningiome du sinus caverneux gauche. Étant don- the trigeminal nerve. A MRI scan of the head re- né la basse prévalence d’un ulcère cornéen neuro- vealed a left cavernous sinus meningioma. Neuro- paralytique comme premier signe d’une pathologie paralytic keratopathy or corneal ulcer is an infre- cérébrale, ce diagnostic est souvent ignoré. Une anam- quent presenting sign of intracranial pathology. The nèse détaillée et un examen ophtalmologique et neu- diagnosis can be missed if the neuroparalytic na- rologique rigoureux révèlent quand même le diagnos- ture of corneal condition is not detected by the oph- tic. thalmologist. KEY WORDS SAMENVATTING Neuroparalytic keratopathy - meningioma We stellen een patiënte voor bij wie een neuropara- MOTS-CLÉS lytisch ulcus het eerste teken was van een cerebraal meningioom. We stelden een cornea ulcus vast in Kératite neuroparalytique - méningiome het linker oog met een gevoelloze cornea en verlies van gevoeligheid en pijnsensatie in de dermatomen bezenuwd door nervus ophthalmicus en maxillaris. Neurologisch onderzoek en NMR-beeldvorming toon- den een meningioom in de linker sinus cavernosus. Aangezien een neuroparalytisch cornea ulcus zel- den als eerste teken van een cerebrale pathologie voorkomt, wordt deze diagnose snel over het hoofd gezien. Een uitgebreide anamnese en een grondig kli- nisch oftalmologisch en neurologisch onderzoek bren- gen echter de diagnose aan het licht.

zzzzzz * Dept. of Ophthalmology, UZ Leuven Kapucijnenvoer 33, 3000 Leuven.

received: 15.01.07 accepted: 07.02.07

Bull. Soc. belge Ophtalmol., 303, 81-86, 2007. 81 INTRODUCTION an ophthalmologist. She had suffered from fi- bromyalgia in the past. In July 2003 her first The cornea is richly supplied by sensory nerve full term healthy child was born by caesarean fibres derived from the ophthalmic division of section. The gestation period was uneventful. the trigeminal nerve and axons from the sym- At the first consultation the best-corrected vi- pathetic ganglion (4, 21). Corneal sensory de- sual acuity was 10/10 RE and 5/10 LE. Ocu- nervation results in decreased epithelium lar examination of the right eye was normal, thickness, poor epithelial wound healing, and and it remained so during the follow-up pe- decreased mitosis of epithelial cells (2, 12, 20, riod. Slitlamp examination of the left eye sho- 25). Similarly, sensory denervation of the con- wed a paracentral corneal ulcer with undermi- junctiva in monkey eyes induces an inflamma- ned edges, but without conjunctival hyperae- tory response characterized by infiltration of the mia or aqueous flare. The left cornea was in- epithelium by neutrophils and macrophages, sensitive to touch by a cotton tip applicator. The and conjunctival tissue disorganization (22). skin dermatome supplied by the first branch of Degenerative changes in the corneal epithe- the left trigeminal nerve was insensitive to touch lium and conjunctiva after traumatic or surgi- and pain stimuli, and hypoesthesic in the der- cal lesions of the trigeminal nerve (11, 23) ma- matome supplied by the second branch of the nifest in a clinical condition known as neuro- trigeminal nerve. Explicit questioning revealed trophic keratitis or keratopathy. Other condi- that epilation of the left eyebrow was painless tions commonly associated with neurotrophic for about one year, and that she had noticed a keratitis are infections by herpes simplex virus transient painless redness of the left eye, and or varicella-zoster virus, diabetes mellitus, mul- a smaller left palpebral fissure, soon after her tiple sclerosis, contact lens wear, chemical burns, child was born. The ocular motility, pupil size trauma, corneal surgery, radiotherapy, leprosy, and pupil reflexes, anterior chamber structu- tumours of the nerve (neurofibroma and me- res and the ocular fundus were normal. The ningioma), aneurysms and cerebrovascular ac- central and peripheral visual fields were in- cidents (1, 10) . tact. A tentative diagnosis of neuroparalytic keratitis was made. Since the patient declined im- In most patients the general medical history mediate admission to the hospital and further and associated systemic signs and symptoms investigations, she was put on DeIcolt eye drops are helpful in the diagnosis of neurotrophic na- 3 times a day and VitA-post ointment twice a ture of the corneal condition. However, in the day. During the following month the corneal ul- absence of any relevant medical antecedents, cer persisted (Figure 1) with deterioration of vi- neurotrophic keratitis can be a major diagnos- sion to 25/100. The left eye had also become tic challenge to the ophthalmologist. A meti- slightly red but there was no discharge. Our pa- culous medical history and a thorough oph- tient now agreed for admission to the hospital thalmic examination, followed by a neurologi- and the topical treatment was changed to Traf- cal and neuroradiologic evaluation, are neces- loxalt ointment once a day, Hylo-comodt eye sary to detect the causative lesion. In this re- drops 5 to 6 times a day and an eye patch. The port we describe a patient with neurotrophic keratitis caused by a cerebral meningioma of the cavernous sinus. This young patient had no other systemic symptoms or signs. CASE REPORT A young woman, 26-years of age, with a history of corneal ulcer in the left eye for one month, was referred to us by an ophthalmologist in the last week of October 2003. The only relevant ophthalmic history was slight redness of the left Figure 1: Slit lamp photograph of the neuroparalytic ulcer eye without any irritation which was treated by on the left eye of our patient.

82 corneal ulcer healed in 6 days with vision im- proving to 7/10. The topical treatment was further continued to protect the ocular surface. In the meantime, clinical neurological examination suggested a partial sinus cavernous syndrome with anaesthesia of V1, hypoesthesia of V2. Nuclear magnetic resonance imaging confirmed the presence of an intracranial mass, measuring 3,1 x 2,9 x 1,9 cm, in the left cavernous sinus suspected to be a meningioma, (Figure 2). The patient was transferred to the department of neurosurgery. In the first week of December 2003 a partial resection of the intracranial mass was carried out. The tumour was not removed in toto because this would have involved sacrificing the left trochlear and the ophthalmic nerves. Histopathological examination confirmed the mass to be a WHO stage 1 fibrous meningioma. Our patient was discharged from the hospital on 9 December 2003 with topical Trafloxalt ointment once dai- ly and Hylo-comodt eye drops 4 times and a Figure 2: NMR of the brains showing a meningioma in the day. Two weeks later the patient reported a wor- left cavernous sinus. sening of the vision of the left eye for a couple of days which was again reduced to 3/10 with recurrence of the corneal ulcer at the same site vember 2004 the patient was not wearing the where the ulcer had been previously. The eye bandage lenses anymore. The corneal ulcer had was now red. Patching of the eye was restar- increased in size with peripheral neovasculari- ted and the frequency of Hylo-comodt instil- sation. The patient insisted upon some kind of lation was raised to 6 times a day. This treat- permanent solution to her problem. On 1 De- ment was successful in healing the ulcer again cember 2004 a conjunctivoplasty by Gunder- quickly. On 19 January 2004, a fluoresceine- son flap was done to cover the left cornea be- positive epithelial defect was detected again on cause of the uncertainty of results by the ne- the previous ulcer site. We decided to induce wer treatment options. There has been no cor- upper eyelid ptosis by botulinum A toxin injec- neal ulceration since then. The vision is hand tion. It was done on 9 February 2004. The pto- movements nearby. Regular neurological and sis induction was incomplete and short lived neuroradiological checkups have not shown tu- but it lead to the healing of the ulcer rapidly mour growth. with visual recovery to 6/10. To achieve longer protection of the corneal surface, a second bo- DISCUSSION tulin injection was given in March, but there was hardly any response in terms of ptosis in- The characteristic clinical feature of neurotrophic duction and the corneal lesion again started to keratopathy is a breakdown of the corneal epi- stain with fluoresceine. The patient started to thelium resulting in an epithelial defect sur- become fed up with patching. In the middle of rounded by a rim of loose epithelium with rolled June 2004 a bandage soft contact lens was ap- up edges and oedema. The defect usually per- plied with Predmycine Pt eye drops 3 times a sists despite of treatment and becomes oval or day. Initially this therapy was effective but the circular in shape. With continued progression patient reported intolerance to the lens. She necrosis, stromal melting and perforation may started taking the lens out before retiring to bed ensue. Lack of redness, pain, discharge, and at night. Several lenses were lost. By mid No- in early stages, absence of stromal infiltration

83 should make one suspect the presence of cor- sometimes be seen for 8 to 10 months, wheth- neal anaesthesia (9) as the cause of the cor- er or not associated with iritis (9). A transient neal changes. painless red eye soon after the delivery report- Reviewing the literature on the pathogenesis of ed by our patient probably corresponded to this neurotrophic keratopathy, Müller et al (21) up- stage. Conjunctival hyperemia should be re- held mainly three hypotheses that may explain garded as a forewarning of future trouble in pa- the corneal changes after corneal denervation. tients with trigeminal nerve lesions. Corneal al- Firstly, corneal desiccation may ensue due to terations may start within 24 hours after the decreased lacrimal secretions and diminished ophthalmic or trigeminal nerve lesions. The blink reflex (14, 16) resulting from impaired clinical picture may resemble one of the fol- corneal sensitivity. Secondly, an abnormal epi- lowing three stages. (1) The first stage is a sig- thelial cell metabolism may be responsible for nificant lack of the corneal luster and the ap- the failure of epithelial cells to resist the ef- pearance of punctate keratopathy (6, 7, 9). Oc- fects of trauma, drying and infection, as epi- casionally the process does not progress fur- thelial cell metabolic activity decreases after ther and resolves into a picture resembling a corneal denervation (26). Finally, the absence diffuse vesicular keratitis or recurrent erosions. of the trophic influence of sensory nerves me- When there is progression, a persistent epithe- diated by neuropeptides like substance-P or va- lial defect appears without (Stage 2) or with sointestinal protein (VIP) may initiate neu- corneal ulceration (stage 3). The areas of de- rotrophic changes. It is believed that the neu- generation are sometimes sharply circum- rotrophic deficit plays the main role in destroy- scribed, known as Gaule’s spots or Dellen when ing the denervated cornea, the cellular meta- in the periphery. Otherwise a rapid and mas- bolic change and increased desiccation having sive exfoliation of the epithelium occurs start- a less important deleterious effect (9, 15, 17, ing in the central cornea, and spreading to in- 21). volve the entire corneal surface apart from a Morphological and metabolic epithelial chang- small rim of epithelium near to the limbus. The es after corneal denervation have been studied denuded surface appears dry, milky and hazy. in a large number of experimental animals (3, It is surrounded by a slightly raised grey ring of 5, 16, 24). The first change to occur is the loss proliferating epithelium. This is the typical pic- of cytoskeletal structures in the superficial squa- ture of neuroparalytic keratitis. In untreated or meous epithelial cells accompanied by the loss neglected cases the entire cornea becomes of cellular adhesions and the loss of cell mi- opaque or a secondary infection may cause ul- gration direction, and intercellular oedema (3, ceration which may hasten perforation of the 5). Consequently increased cell desquamation cornea. The course of disease is slow and chron- occurs due to the weakened cellular attach- ic with many relapses. Because of associated ments which result in a stippled corneal sur- anesthesia it is characterized by the absence face with multiple punctuate epithelial defects, of acute symptoms (9). and the accumulated epithelial defects may contribute to the tendency to form recurrent The management of neuroparalytic keratitis is erosions (3, 5). Interruption of the epithelial one of the most difficult and challenging among nerve supply causes a reduction in the meta- all corneal diseases, because of the lack of spe- bolic activity of the cells (26) with subsequent cific treatment. The best options are preserva- decreased oxygen uptake rate and altered hy- tive-free artificial tears, prophylactic topical an- poxic swelling response (13, 21). All these fac- tibiotic drops and eyelid closure. After a suc- tors contribute to a decreased repair capability cessful lid closure, a rapid improvement fol- following a standardized epithelial abrasion. In lows almost immediately (9, 18). Currently, addition, exposure and drying may enhance the ptosis induction by botulinum A toxin for tem- chances of corneal ulceration (5). porary eyelid closure is preferred to a tarsorra- The corneal degenerative changes generally de- phy because the later is more disfiguring. Re- velop within the first 6 months after lesions of peated botulinum A toxin injections in our pa- the trigeminal nerve. As an immediate response tient failed to induce adequate ptosis. There- to the nerve injury, conjunctival hyperaemia can fore, we had to resort to other management mo-

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