- Email: [email protected]
Accommodation Defect in Wilson's Disease
ACCOMMODATION DEFECT IN WILSON'S DISEASE TERENCE
G.
KLINGELE, M.D., STEVEN A. NEWMAN, M.D., AND RONALD M. BURDE, M.D. St. Louis, Missouri
Wilson's disease is a hereditary disor- mus, cranial nerve palsies, and other der of copper metabolism, characterized movement disorders). One of their paby a progressive degeneration of the tients had "paralysis of accommodation central nervous system, and associated and ataxic movements of the eyes." with hepatic cirrhosis. The neurologic We describe a patient with Wilson's syndrome frequently includes difficulty disease who complained of difficulty speaking, swallowing, and chewing. A reading and who had markedly reduced characteristic tremor of the wrists and amplitude of accommodation. shoulders is increased on voluntary action. Rigidity is common. Inappropriate CASE REPORT laughing or crying is seen. A 22-year-old man was referred here for evaluation Ocular findings include a pigmented suspected Wilson's disease. He had noted the corneal ring, which is almost always of onset of upper extremity tremor in October 1977. He present in cases with neurologic involve- had a one-year history of mild dysarthria, and ment (97%), and pigment under the lens personality and behavioral changes. There was a family history of psychiatric disorders. The patient capsule (17%).1 Wilson.! Goldberg, and was receiving no medications at the time of examinavon Noorden," and Walsh and Hoyt' all tion and had received no tranquilizers, sedatives, commented on the absence of involve- antidepressants, or any other medications during the preceding several weeks. Physical examination in ment of ocular muscles. Walsh and Hoyt' April 1978 showed slurred, ataxic speech, mild stated that this was "most remarkable in "wing-beating" tremor, some coarsening in the view of the nature of the pathologic finger-to-nose testing and difficulty with tandem gait. Liver scan showed an enlarged liver, the serum changes. " Occasional references have ceruloplasmin was less than 5 mg/dl (normal, 21 to been made to jerky oscillations of the 43 mg/dl), serum copper was 40 jLgldl (normal, 80 to eyes, involuntary upgaze, paresis of up- 100 jLgldl); and 24-hour urine copper was 476 jLg < 30). At the time of his first ophthalmic gaze, and slowed saccadic move- (normal examination in April 1978, he described a two-year ments.P? history of blurred near vision. Uncorrected visual Wiebers, Hollenhorst, and Coldstein! acuity was 6/6 (20/20) in both eyes, but the patient only read 6/30 (201100) near equivalent (J 10) at recently reported ophthalmologic abnor- could 32 to 44 em. Manifest refraction showed the patient malities in 53 patients with Wilson's to be slightly hyperopic in both eyes: R.E.: + 1.00 + disease and emphasized the presence of 0.25 X 90 degrees; and L.E.: +1.00 + 0.25 X 90 degrees. This was later confirmed with cycloplegic corneal rings and the absence of other examination using 1% tropicamide.) Accommodative ophthalmologic signs (such as nystag- range measured by Prince rule was 2.5 diopters in
From the Departments of Ophthalmology (Drs. Kltngele, Newman, and Burde) and Neurology (Dr. Burde), Washington University School of Medicine, St. Louis, Missouri. This study was supported in part by a grant from Research to Prevent Blindness, Inc., New York, New York. Reprint requests to Ronald M. Burde, M.D., Department of Ophthalmology, Box 8096, 660 S. Euclid Ave., St. Louis, MO 63110.
22
the right eye and 3.0 diopters in the left eye with correction. Pupillary reactions to light and near stimulus were normal. The patient was orthophoric at distance, but there was a five-prism diopter exophoria at near with a near point of convergence measured at 25 em. Saccadic movements were mildly hypometric, and there was microsaceadic pursuit and upbeating nystagmus on upgaze. Slit-lamp examination confirmed the presence of a Kayser-Fleischer ring. There was no cataract. Results of examination of the retina were normal. Therapy was initiated with penicillamine, a low copper diet, potassium sulfide, and pyridoxine HCI.
AMERICAN JOURNAL OF OPHTHALMOLOGY 90:22-24, 1980
VOL. 90, NO. 1
ACCOMMODATION DEFECT IN WILSON'S DISEASE
DISCUSSION
Goldberg and von Noorden" emphasized the "remarkable normality of complex oculomotor functions in patients with Wilson's disease." However, they did not report any attempts to measure accommodative amplitude in their patients. Wiebers, Hollenhorst, and Goldstein! found one of their patients, who complained of inability to read, to have "paralysis of accommodation," but apparently did not test accommodation in any of the other patients. Heine'' reported a case of internal ophthalmoplegia but did not measure accommodation. The neurologic pathways subs erving accommodation begin in the retina and afferent fibers and travel up the optic nerve, chiasm, and tracts. They are relayed in the lateral geniculate body where a further neuron travels to the calcarine cortex; there, a relay is made to the prestriate area. From this region, the reflex pathways travel down the internal corticotectal tract to the diencephalic region, where a connection is made with the caudal portion of the parasympathetic component of the oculomotor nuclear complex, the Edinger-Westphal nucleus. From the Edinger-Westphal nucleus the afferent path travels down the oculomotor nerve, and relays in the ciliary ganglion from which fibers reach the pupillary sphincter and ciliary muscles. 9 Many diseases diminish accommodation. 9,10 Ocular problems such as iridocyclitis, congenital glaucoma, and trauma may do so by injuring the ciliary body. A variety of drugs and toxic chemicals cause cycloplegia. Myotonic dystrophy and myasthenia gravis may have a minimal effect on accommodation. Botulism, syphilis, tuberculosis, and leprosy can cause paralysis of accommodation by injury to the oculomotor nerve or nucleus. Viral disease such as mumps, hepatitis, herpes zoster, poliomyelitis, and
23
encephalitis occasionally disturb accommodation, as do diabetic and alcoholic neuropathy. Pupillary and ciliary musculature may be paretic in the ophthalmoplegic form of acute idiopathic polyneuritis. Lesions of the tectal region, such as pinealomas and astrocytomas, commonly cause supranuclear vertical eye movement problems and may interfere with accommodation. Acute hemorrhagic anterior polio encephalitis of Wernicke is sometimes associated with accommodative paralysis. Finally, cerebral concussion and craniocervical extension injuries may be followed by symptoms of accommodative disturbance. Pathologic changes in Wilson's disease are most prominent in the corpus striatum. However, degeneration may be present in the diencephalon and upper brainstem. The thalamus, red nucleus, and dentate nucleus are occasionally involved." Greenfield" described shrinkage of the corpus striatum involving the putamen and caudate nucleus bilaterally. Microscopic examination also showed degeneration in the tracts leading from the putamen to the red nucleus and the corpus luysii, and to the posterior longitudinal bundles and superior cerebellar peduncles. In a normal individual, accommodative amplitude decreases with age from about 12 diopters at age 8 years to 2 diopters at age 50 years." Emmetropic individuals usually develop symptoms of accommodative weakness between the ages of 40 and 45 years. Our patient, at age 22 years, would be expected to have an amplitude of accommodation between 8 and 12 diopters," but he had only 2.5 to 3 diopters. He had had symptoms of deficient accommodation lasting several months. There was no evidence of any other disorder that might explain his accommodative weakness, and he had not received any known cycloplegic agents before our examination.
24
AMERICAN JOURNAL OF OPHTHALMOLOGY
However, primary insufficiency of accommodation is occasionally seen in young adults and cannot be absolutely excluded here, although we consider it quite unlikely. Our patient had signs of extensive disease in the mesencephalon and brainstem tegmentum. These included the characteristic tremor, dysarthria, gait disturbance, hypometric saccades, microsaccadic pursuit movements, and diminished convergence in addition to a reduced amplitude of accommodation. However, normal ductions and normal pupillary reactions suggest that the oculomotor nuclear complex was spared. Other authors' have suggested that disturbance of ocular motility and the near reflex might be found in Wilson's disease where descending pathways from the occipital cortex could be interrupted in the diencephalon or mesencephalon. We agree, and we believe that the clinical findings in our patient point to a supranuclear defect in accommodation. To the best of our knowledge there are no previous published reports of measurements of accommodation in Wilson's disease. We believe a significant percentage of patients with Wilson's disease may have a disturbance of accommodation, which is overlooked because the patient is young enough to have a large accommodative reserve or is so neurologically disabled that a careful visual system examination is not possible. We suggest that measurements of accommodation should be part of the evaluation of sus-
JULY, 1980
pected Wilson's disease whenever clinically possible. SUMMARY
A 22-year-old man with Wilson's disease had blurred vision caused by a defect of accommodation that we believed to be supranuclear in origin. REFERENCES 1. Wiebers, D. 0., Hollenhorst, R. W., and Goldstein, N. P.: The ophthalmologic manifestations of Wilson's disease. Mayo Clin. Proc. 52:409, 1977. 2. Wilson, S. A. K.: Progressive lenticular degeneration. A familial nervous disease associated with cirrhosis of the liver. Brain 34:295, 1912. 3. Goldberg, M. F., and von Noorden, G. K.: Ophthalmologic findings in Wilson's hepatolenticular degeneration with emphasis on ocular motility. Arch. Ophthalmol. 75:162, 1966. 4. Walsh, F. B., and Hoyt, W. F.: Clinical Neuro-Ophthalmology, vol. 2, 3rd ed. Baltimore, Williams and Wilkins Co., 1969, p. 1038. 5. Segal, P., Ruszkowski, M., Berger, S., and Masiak, M.: Abortive form of Wilson's syndrome. With dark adaptation disturbances. Am. J. Ophthalmol. 44:623, 1957. 6. Ruder, W.: Seltene Augen Veriinderrungen. Beim Hepatolentikularen Syndrome. Klin. Monatsbl. Augenheilkd. 125:472, 1954. 7. Kirkham, T. H., and Kamin, D. F.: Slow saccades in Wilson's disease. J. Neurol. Neurosurg. Psychiatr. 37:191, 1974. 8. Heine, L.: Ueber Augenveriinderungen bel Pseudosklerose. (Kayser-Fleischer Ring, Pupillenund Akkomodationsstorung, Blickhebungslihmung). Klin. Monatsbl. Augenheilkd. 31:433, 1933. 9. Duke-Elder, S., and Scott, G. I.: NeuroOphthalmology. In System of Ophthalmology, vol. 12. St. Louis, C. V. Mosby Co., 1971, p. 698. 10. Walsh, F. G., and Hoyt, W. F.: Clinical Neuro-Ophthalmology, vol. 1, 3rd ed. Baltimore, Williams and Wilkins Co., 1969, p. 549. 11. Robbins, S. L.: Pathology, 3rd ed. Philadelphia, W. B. Saunders, 1967, p. 1428. 12. Greenfield, J. G.: On progressive lenticular degeneration. Q. J. Med. 17:385, 1923. 13. Duane, A.: Are the current theories of accommodation correct? Am. J. Ophthalmol. 8:196, 1925.
G.
KLINGELE, M.D., STEVEN A. NEWMAN, M.D., AND RONALD M. BURDE, M.D. St. Louis, Missouri
Wilson's disease is a hereditary disor- mus, cranial nerve palsies, and other der of copper metabolism, characterized movement disorders). One of their paby a progressive degeneration of the tients had "paralysis of accommodation central nervous system, and associated and ataxic movements of the eyes." with hepatic cirrhosis. The neurologic We describe a patient with Wilson's syndrome frequently includes difficulty disease who complained of difficulty speaking, swallowing, and chewing. A reading and who had markedly reduced characteristic tremor of the wrists and amplitude of accommodation. shoulders is increased on voluntary action. Rigidity is common. Inappropriate CASE REPORT laughing or crying is seen. A 22-year-old man was referred here for evaluation Ocular findings include a pigmented suspected Wilson's disease. He had noted the corneal ring, which is almost always of onset of upper extremity tremor in October 1977. He present in cases with neurologic involve- had a one-year history of mild dysarthria, and ment (97%), and pigment under the lens personality and behavioral changes. There was a family history of psychiatric disorders. The patient capsule (17%).1 Wilson.! Goldberg, and was receiving no medications at the time of examinavon Noorden," and Walsh and Hoyt' all tion and had received no tranquilizers, sedatives, commented on the absence of involve- antidepressants, or any other medications during the preceding several weeks. Physical examination in ment of ocular muscles. Walsh and Hoyt' April 1978 showed slurred, ataxic speech, mild stated that this was "most remarkable in "wing-beating" tremor, some coarsening in the view of the nature of the pathologic finger-to-nose testing and difficulty with tandem gait. Liver scan showed an enlarged liver, the serum changes. " Occasional references have ceruloplasmin was less than 5 mg/dl (normal, 21 to been made to jerky oscillations of the 43 mg/dl), serum copper was 40 jLgldl (normal, 80 to eyes, involuntary upgaze, paresis of up- 100 jLgldl); and 24-hour urine copper was 476 jLg < 30). At the time of his first ophthalmic gaze, and slowed saccadic move- (normal examination in April 1978, he described a two-year ments.P? history of blurred near vision. Uncorrected visual Wiebers, Hollenhorst, and Coldstein! acuity was 6/6 (20/20) in both eyes, but the patient only read 6/30 (201100) near equivalent (J 10) at recently reported ophthalmologic abnor- could 32 to 44 em. Manifest refraction showed the patient malities in 53 patients with Wilson's to be slightly hyperopic in both eyes: R.E.: + 1.00 + disease and emphasized the presence of 0.25 X 90 degrees; and L.E.: +1.00 + 0.25 X 90 degrees. This was later confirmed with cycloplegic corneal rings and the absence of other examination using 1% tropicamide.) Accommodative ophthalmologic signs (such as nystag- range measured by Prince rule was 2.5 diopters in
From the Departments of Ophthalmology (Drs. Kltngele, Newman, and Burde) and Neurology (Dr. Burde), Washington University School of Medicine, St. Louis, Missouri. This study was supported in part by a grant from Research to Prevent Blindness, Inc., New York, New York. Reprint requests to Ronald M. Burde, M.D., Department of Ophthalmology, Box 8096, 660 S. Euclid Ave., St. Louis, MO 63110.
22
the right eye and 3.0 diopters in the left eye with correction. Pupillary reactions to light and near stimulus were normal. The patient was orthophoric at distance, but there was a five-prism diopter exophoria at near with a near point of convergence measured at 25 em. Saccadic movements were mildly hypometric, and there was microsaceadic pursuit and upbeating nystagmus on upgaze. Slit-lamp examination confirmed the presence of a Kayser-Fleischer ring. There was no cataract. Results of examination of the retina were normal. Therapy was initiated with penicillamine, a low copper diet, potassium sulfide, and pyridoxine HCI.
AMERICAN JOURNAL OF OPHTHALMOLOGY 90:22-24, 1980
VOL. 90, NO. 1
ACCOMMODATION DEFECT IN WILSON'S DISEASE
DISCUSSION
Goldberg and von Noorden" emphasized the "remarkable normality of complex oculomotor functions in patients with Wilson's disease." However, they did not report any attempts to measure accommodative amplitude in their patients. Wiebers, Hollenhorst, and Goldstein! found one of their patients, who complained of inability to read, to have "paralysis of accommodation," but apparently did not test accommodation in any of the other patients. Heine'' reported a case of internal ophthalmoplegia but did not measure accommodation. The neurologic pathways subs erving accommodation begin in the retina and afferent fibers and travel up the optic nerve, chiasm, and tracts. They are relayed in the lateral geniculate body where a further neuron travels to the calcarine cortex; there, a relay is made to the prestriate area. From this region, the reflex pathways travel down the internal corticotectal tract to the diencephalic region, where a connection is made with the caudal portion of the parasympathetic component of the oculomotor nuclear complex, the Edinger-Westphal nucleus. From the Edinger-Westphal nucleus the afferent path travels down the oculomotor nerve, and relays in the ciliary ganglion from which fibers reach the pupillary sphincter and ciliary muscles. 9 Many diseases diminish accommodation. 9,10 Ocular problems such as iridocyclitis, congenital glaucoma, and trauma may do so by injuring the ciliary body. A variety of drugs and toxic chemicals cause cycloplegia. Myotonic dystrophy and myasthenia gravis may have a minimal effect on accommodation. Botulism, syphilis, tuberculosis, and leprosy can cause paralysis of accommodation by injury to the oculomotor nerve or nucleus. Viral disease such as mumps, hepatitis, herpes zoster, poliomyelitis, and
23
encephalitis occasionally disturb accommodation, as do diabetic and alcoholic neuropathy. Pupillary and ciliary musculature may be paretic in the ophthalmoplegic form of acute idiopathic polyneuritis. Lesions of the tectal region, such as pinealomas and astrocytomas, commonly cause supranuclear vertical eye movement problems and may interfere with accommodation. Acute hemorrhagic anterior polio encephalitis of Wernicke is sometimes associated with accommodative paralysis. Finally, cerebral concussion and craniocervical extension injuries may be followed by symptoms of accommodative disturbance. Pathologic changes in Wilson's disease are most prominent in the corpus striatum. However, degeneration may be present in the diencephalon and upper brainstem. The thalamus, red nucleus, and dentate nucleus are occasionally involved." Greenfield" described shrinkage of the corpus striatum involving the putamen and caudate nucleus bilaterally. Microscopic examination also showed degeneration in the tracts leading from the putamen to the red nucleus and the corpus luysii, and to the posterior longitudinal bundles and superior cerebellar peduncles. In a normal individual, accommodative amplitude decreases with age from about 12 diopters at age 8 years to 2 diopters at age 50 years." Emmetropic individuals usually develop symptoms of accommodative weakness between the ages of 40 and 45 years. Our patient, at age 22 years, would be expected to have an amplitude of accommodation between 8 and 12 diopters," but he had only 2.5 to 3 diopters. He had had symptoms of deficient accommodation lasting several months. There was no evidence of any other disorder that might explain his accommodative weakness, and he had not received any known cycloplegic agents before our examination.
24
AMERICAN JOURNAL OF OPHTHALMOLOGY
However, primary insufficiency of accommodation is occasionally seen in young adults and cannot be absolutely excluded here, although we consider it quite unlikely. Our patient had signs of extensive disease in the mesencephalon and brainstem tegmentum. These included the characteristic tremor, dysarthria, gait disturbance, hypometric saccades, microsaccadic pursuit movements, and diminished convergence in addition to a reduced amplitude of accommodation. However, normal ductions and normal pupillary reactions suggest that the oculomotor nuclear complex was spared. Other authors' have suggested that disturbance of ocular motility and the near reflex might be found in Wilson's disease where descending pathways from the occipital cortex could be interrupted in the diencephalon or mesencephalon. We agree, and we believe that the clinical findings in our patient point to a supranuclear defect in accommodation. To the best of our knowledge there are no previous published reports of measurements of accommodation in Wilson's disease. We believe a significant percentage of patients with Wilson's disease may have a disturbance of accommodation, which is overlooked because the patient is young enough to have a large accommodative reserve or is so neurologically disabled that a careful visual system examination is not possible. We suggest that measurements of accommodation should be part of the evaluation of sus-
JULY, 1980
pected Wilson's disease whenever clinically possible. SUMMARY
A 22-year-old man with Wilson's disease had blurred vision caused by a defect of accommodation that we believed to be supranuclear in origin. REFERENCES 1. Wiebers, D. 0., Hollenhorst, R. W., and Goldstein, N. P.: The ophthalmologic manifestations of Wilson's disease. Mayo Clin. Proc. 52:409, 1977. 2. Wilson, S. A. K.: Progressive lenticular degeneration. A familial nervous disease associated with cirrhosis of the liver. Brain 34:295, 1912. 3. Goldberg, M. F., and von Noorden, G. K.: Ophthalmologic findings in Wilson's hepatolenticular degeneration with emphasis on ocular motility. Arch. Ophthalmol. 75:162, 1966. 4. Walsh, F. B., and Hoyt, W. F.: Clinical Neuro-Ophthalmology, vol. 2, 3rd ed. Baltimore, Williams and Wilkins Co., 1969, p. 1038. 5. Segal, P., Ruszkowski, M., Berger, S., and Masiak, M.: Abortive form of Wilson's syndrome. With dark adaptation disturbances. Am. J. Ophthalmol. 44:623, 1957. 6. Ruder, W.: Seltene Augen Veriinderrungen. Beim Hepatolentikularen Syndrome. Klin. Monatsbl. Augenheilkd. 125:472, 1954. 7. Kirkham, T. H., and Kamin, D. F.: Slow saccades in Wilson's disease. J. Neurol. Neurosurg. Psychiatr. 37:191, 1974. 8. Heine, L.: Ueber Augenveriinderungen bel Pseudosklerose. (Kayser-Fleischer Ring, Pupillenund Akkomodationsstorung, Blickhebungslihmung). Klin. Monatsbl. Augenheilkd. 31:433, 1933. 9. Duke-Elder, S., and Scott, G. I.: NeuroOphthalmology. In System of Ophthalmology, vol. 12. St. Louis, C. V. Mosby Co., 1971, p. 698. 10. Walsh, F. G., and Hoyt, W. F.: Clinical Neuro-Ophthalmology, vol. 1, 3rd ed. Baltimore, Williams and Wilkins Co., 1969, p. 549. 11. Robbins, S. L.: Pathology, 3rd ed. Philadelphia, W. B. Saunders, 1967, p. 1428. 12. Greenfield, J. G.: On progressive lenticular degeneration. Q. J. Med. 17:385, 1923. 13. Duane, A.: Are the current theories of accommodation correct? Am. J. Ophthalmol. 8:196, 1925.