Journal of Neuro-Ophthalmology, September 1990, Volume 10, Issue 3

Enhanced ptosis in Fisher's syndrome after Epstein-Barr virus infection.

A 20-year-old woman presented with bilateral ptosis, total ophthalmoplegia, cerebellar symptoms, and hyporeflexia, indicating Fisher's syndrome. She had been diagnosed with infectious mononucleosis 2 months previously. Increased Epstein-Barr virus (EBV) titer was noted, and the Epstein-Barr virus-associated nuclear antigen (EBNA) became positive during the clinical course. Apparent light-near dissociation of the pupils was noted and accommodation was intact. During pharmacological tests with topical application to the eye by sympathomimetic or parasympathomimetic drugs, the pupils showed no supersensitivity, indicating possible central disorder. Enhanced ptosis was noted in each eye and this condition was aggravated by manually lifting the eyelids. The recovery latency time of this enhanced ptosis was approximately 180 ms, indicating a central polysynaptic process to possibly be the cause. Although this condition is considered specifically associated with peripheral neural or muscle diseases, the present case would indicate a central disorder as a possible mechanism.

Journal of Clini"' l Neuro- ophthalmology 10( 3): 197- 200, 1990. © 1990 Raven Press, Ltd., New York Enhanced Ptosis in Fisher's Syndrome After Epstein- Barr Virus Infection Hitoshi Ishikawa, M. D., Masato Wakakura, M. D. D. Sc. and Satoshi Ishikawa, M. D. D. Se. A 20- year- old woman presented with bilateral ptosis, total ophthalmoplegia, cerebellar symptoms, and hy­poreflexia, indicating Fisher's syndrome. She had been diagnosed with infectious mononucleosis 2 months pre­viously. Increased Epstein- Barr virus ( EBV) titer was noted, and the Epstein- Barr virus- associated nuclear an­tigen ( EBNA) became positive during the clinical course. Apparent light- near dissociation of the pupils was noted and accommodation was intact. During pharmacological tests with topical application to the eye by sympathomi­metic or parasympathomimetic drugs, the pupils showed no supersensitivity, indicating possible central disorder. Enhanced ptosis was noted in each eye and this condition was aggravated by manually lifting the eyelids. The recovery latency time of this enhanced pto­sis was - 180 ms, indicating a central polysynaptic pro­cess to possibly be the cause. Although this condition is considered specifically associated with peripheral neural or muscle diseases, the present case would indicate a central disorder as a possible mechanism. Key Words: Enhanced ptosis- Fisher's syndrome­Infectious mononucleosis- Epstein- Barr virus­Light- near dissociation- Central disorder. From the Department of Ophthalmology, School of Medi­cine, Kitasato University, Sagamihara, Kanagawa, Japan. Address correspondence and reprint requests to Dr. H. Ishikawa at Department of Ophthalmology, School of MedI­cine, Kitasato University, 1- 15- 1 Kitasato, Sagamihara, Kana­gawa 228, Japan. 197 Fisher's syndrome, possibly a postinfectious dis­ease, is characterized by external ophthalmople­gia, ataxia, and areflexia ( 1). Although the patho­genesis is usually quite difficult to identify, one case associated with Epstein- Barr virus ( EBV) in­fection has been reported ( 2). Peripheral ( 3) or cen­tral ( 4) lesions or both ( 5,6) may possibly be seen in Fisher's syndrome. Recently, abnormal lid move­ment of enhanced ptosis has been reported in pe­ripheral neuromuscular diseases of myasthenia gravis ( 7), senile ptosis ( 8), and ocular myopathy ( 9). Enhanced ptosis is an unusual condition in which ptosis worsens on one side when the oppo­site eyelid is maintained elevated. To date, the Fisher's syndrome has not been found associated with this condition. The various symptoms, in­cluding enhanced ptosis, in the present case indi­cate the possible presence of central lesions. CASE REPORT A 20- year- old woman was admitted to a local hospital on July 20, 1988, where she stayed for 2 weeks, due to sore throat, general malaise, and swollen submandibular lymph nodes. Clinical and hematological diagnosis was infectious mononu­cleosis. Two months later, on September 18, she had a cough, general fatigue, and mild fever. The following morning, double vision in all directions was noted. There was transient numbness in the distal portions of all the extremities, and this may have been a factor in the difficulty experienced by the patient in walking. The double vision became gradually worse, prompting her to come to our department on September 20 for examination. She was admitted to Kitasato University Hospital. Ophthalmologically, her corrected visual acuity was 20/ 20 in each eye. Bilateral mild ptosis was present. Eye position indicated orthophoria, but 198 H. ISHIKAWA ET AI. the movement of each eye showed total ophthal­moplegia on September 20. There was no pupillary reaction to light, but the near point of pupillary response was intact. The near point of conver­gence was at - 10 cm. Bell's phenomenon was pos­itive in each eye. Bilateral enhanced ptosis was noted and is described below in detail. The ptosis was not enhanced by sustained upward gaze. Pto­sis and ophthalmoplegia did not improve in re­sponse to an intravenous injection of 10 mg edro­phonium chloride. Several cerebellar signs were noted to be posi­tive. The nose- finger- nose test could only be poorly performed on either side. Heel- to- knee test results were also poor on each side. Staggered gait towards the right and inability to stand on one foot were noted. Gastrocnemius and anterior tibial muscle force were reduced. Knee and achilles ten­don reflexes were diminished on each side. No marked sensory abnormality could be found. Thus, the clinical diagnosis was Fisher's syndrome even though cerebrospinal fluid showed no change. Serodiagnostic Examination EBV titers by immunofluorescence with viral capsid antigen ( VCA) testing were as follows: on September 21, VCA- IgG was 1: 320 and on October 1, 1: 320, and on October 5, it was also 1: 320. VCA­IgM had also increased to 1: 40 on October 5. EBV­associated nuclear antigen ( EBNA) was negative on September 21, but on both October 1 and 5, the EBNA titer was a high 1: 40. It was thus evident that the patient had recently become infected with EBV. Blood analysis of other viruses showed nor­mal findings. Serum thyroid function tests such as thyroid- stimulating hormone, triiodothyronine, and thyroxine were also normal. Neuro- ophthalmological Examination 1. Eye movement Ophthalmoplegia slightly regressed 2 weeks af­ter admission. An electrooculography test indi­cated a defective smooth pursuit in both vertical and horizontal directions. However, saccadic movement showed improvement particularly in the horizontal direction. Doll's eye phenomenon, initially absent, was normal by September 30. 2. Pupil and Accommodation An infrared video- pupillography ( Iriscorder, C­2515, Hamamatsu) conducted on September 23 JClin Neuro- ophthalmol. Vol. 10. No, 3. 1990 confirmed each pupil diameter to be largE: ill a dark room, 8.6 mm in the right and 9.0 mm in the left. Neither eye showed light reflex. Supersensitivity of the pupil could be detected neither by a para­sympathomimetic eye drop with 0.125% pilo­carpine hydrochloride nor a sympathomimetic eye drop with 1.25% I- epinephrine. A quasi- static recording ( 10) of accommodation using a modification of a commercially available automated refractometer ( Autorefractometer, AR­2000, Nidek) was made to examine the dynamic functions of accommodation. The attached iris­corder was able to register simultaneously pupil­lary response during an accommodative stimulus. The target stimulus was moved at a velocity of 0.2 diopters ( O)/ s. The amplitude of accommodation was 10.2 0 in the right eye and 10.5 0 in the left eye ( Fig. 1). Quasi- static accommodative response was completely normal for the age of the patient. Throughout the full range of accommodative stim­uli, each pupil constricted well, from 8.0 to 4.1 mm in diameter for the right, and from 8.5 to 3.9 mm for the left eye ( Fig. 1). These results clearly show dissociation between pupillary light reflex and pu­pillary accommodative response. 3. Enhanced ptosis Fig. 2 shows enhanced ptosis on September 20. Contralateral ptosis became aggravated on manu­ally lifting either eyelid in either the light or dark, with or without fixation. An attempt was made to determine the time sequence of this abnormal eye lid movement using the solid state image sensor described by Niida et al. ( 11). The results are shown in Fig. 3. Since the trigger point of this movement could not be easily determined, the la­tency time required for recovery from enhanced ptosis was measured following the release of an elevated eyelid and found to be about 180 ms. En­hanced ptosis completely disappeared with regres­sion of upward gaze palsy. DISCUSSION EBV is a herpes- like virus that causes infectious mononucleosis. The course of this disease may be complicated by various neurological disorders, such as Guillain- Barre's syndrome, meningitis, and transverse myelitis ( 12). Papilledema ( 13) and optic neuritis ( 1:>-- 15) have also been reported. Slavic and Shapiro ( 2) found one case of Fisher's syndrome apparently accompanied by EBV infec­tion but without indication of infectious mononu­cleosis. In the present case, infectious mononucle- ENHANCED PTOSIS IN FISHER'S SYNDROME 199 5 10 FIG. 1. Quasi- static accommodative re­sponse of the right and left eyes and pu­pillary response to the same stimulus. ( top) Accommodative response; ( bottom) Pupillary response. AR, Accommodative response; AS, Accommodative stimulus; PO, Pupillary diameter. 1(. AS ( 0) ; 0 AS( O) 5 PO ( mm) o Lett aye AR ( 0) 5 10 AS ( 0) ( I PO ( mm) o osis was diagnosed clinically 2 months before the appearance of ocular and neurological symptoms. Positive viral capsid antigen IgM, implying an ac­tive or persistent EBV infection ( 16), was evident after the manifestation of neurological symptoms. That the EBNA titer became positive during the clinical course of the patient is also a significant finding. Although the pupils of the patient were incapable of response to light, near- response ap­peared normal, and this was confirmed quantita­tively. Light- near dissociation is a complication seen in Fisher's syndrome ( 17), but the accommo­dation system in Fisher's syndrome has not been quantitatively shown to be normal, except in the present study. Light- near dissociation may gener­ally be interpreted as either a peripheral mecha­nism or central mechanism. However, the com-plete dissociation noted here would rather indicate the type of central disorder quite often observed in the dorsal midbrain syndrome. The absence of pharmacological supersensitivity in the pupillary system should exclude the possibility of a periph­erallesion. " Enhanced ptosis," as termed by Gorelick et a1. ( 7) was another symptom of interest in the present patient. While the condition of upward gaze palsy persisted, enhanced ptosis could be seen in both eyes. This was initially considered to be due to a peripheral lesion, and in fact, all reported cases to date indicate peripheral neural or muscular disor­ders for this condition ( 7- 9). The mechanism for enhanced ptosis can perhaps be explained by Her­ing's law of equal innervation ( 18), assuming pe­ripheral diseases are the cause. However, en- FIG. 2. Photograph of en­hanced ptosis on September 22, 1988. As indicated by the position of eyebrow, her mild ptosis of both eyes was com­pensated with use of the frontal muscle ( top). The condition worsened on one side when the eyelid on the other side was maintained elevated ( bottom). Compare the aperture of the lid at the primary position without elevation. J Gin Neuro- ophthalmol, Vol. 10. No. 3. 1990 200 1 H. ISHIKAWA ET AL. 1000msec RE--__....!..~ Forced open ~ : '-------- Normal aperture of the lid LE -----.,.....:"' 7-:~ ormal aperture of the lid Enhanced ptosis ~ "" 2 Latency time 180msec FIG. 3. Recording of upper eyelid movement showing the recovery phase of enhanced ptosis. Arrow 1 indicates the point from which the finger was re­moved from the right upperlid. Arrow 2 indicates the point from which left eye­lid movement started. The latency time was 180 ms. hanced ptosis was evident in the present Fisher's syndrome characterized by greater involvement of central disorders. Moreover, the latency time was 180 ms. These features would thus appear to arise from a polysynaptic process rather than a simple reflex arc. Two types of enhanced ptosis have been indicated by electromyographic study ( 18). One in­dicates abnormal interaction between the oculo­motor nerve and facial nerve, possibly through central control. The type may be essentiaUy the same as in our case report. 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