| OCR Text |
Show Journal of Neuro- Ophthalmology 17( 1): 44- 46, 1997. © 1997 Lippincott- Raven Publishers, Philadelphia Chronic Internuclear Ophthalmoplegia A Manifestation of D- penicillamine Cerebral Vasculitis Misha Pless, M. D., and Thomas Sandson, M. D. Key Words: Cerebral vasculitis- D- penicillamine- Eye movements- Internuclear ophthalmoplegia. Chronic eye movement disorders may occur in allergic cerebral vasculitis ( 1,2). To the best of our knowledge, we report the first case of a patient in whom an internuclear ophthalmoplegia ( INO) heralded widespread central and peripheral nervous system hypersensitivity to D- penicillamine. A lupus- like necrotizing vasculitis closely resembling periarteritis nodosa is a feared but rare complication of D- penicillamine therapy. Treatment should be halted if stroke- like events supervene. CASE REPORT A 33- year- old woman was admitted because of nausea and oscillopsia. At age 26 years, she was diagnosed as having Wilson's disease when Kayser- Fleisher rings were discovered during an evaluation for dysarthria and ataxia. A brother had been diagnosed with Wilson's disease earlier. She was started on D- penicillamine, which reversed her symptoms; the corneal rings disappeared. She was treated from age 26 until 4 weeks before admission, when it was discontinued because of nausea, headaches, intermittent diplopia, and tinnitus. A neurological examination was normal. Brain magnetic Manuscript received February 5, 1996; accepted March 15, 1996. From the Neurology Division, Ncuro- Ophlhalmology Division, Harvard Medical School and Brigham and Women's Hospital ( M. P.), and the Department of Neurology, Harvard Medical School and Beth Israel Hospital ( T. S.), Boston, Massachusetts. Address correspondence and reprint requests to Dr. Misha Pless, Neurology Division, 75 Francis St., Brigham and Women's Hospital, Boston, MA 02115, U. S. A. resonance imaging ( MRI) showed no lesions. Trien-tine was substituted, and her symptoms resolved. Consideration was given to a D- penicillamine-induced myasthenic syndrome; however, electromyography with repetitive stimulation and acetylcholine receptor antibody titers were normal. Shortly after the reinstitution of penicillamine therapy 2 weeks before admission, she noticed oscillations of the environment. On examination the patient looked frail. She had a right INO, upbeat nystagmus, limitation of up-gaze, and light- near dissociation of the pupils. Her cerebrospinal fluid contained 62 red blood cells and 15 white blood cells per mm3 ( mostly polymorphonuclear leukocytes), 52 mg% glucose, and 81 mg% protein. The next day she became confused and for 12 h she had a right hemiparesis, but the ocular motor abnormalities had vanished. Three days later she became febrile to 104° F. The right hemiparesis and eye movement disturbances reappeared. Reexamination of the cerebrospinal fluid showed a similar cellular formula and an increase in protein content to 364 mg%. Bacterial and viral cultures were negative on both spinal fluid examinations. Brain MRI with the i. v. administration of Gadolinium showed widespread bilateral deep hemispheric and brainstem foci of areas with increased T2- weighted signal ( Figs. 1 and 2). These lesions enhanced on T r weighted sequences. Magnetic resonance angiography of the intracranial circulation showed multiple areas of narrowing in the left middle cerebral artery. Over the next week she developed severe bilateral sciatic and ulnar neuropathies. A sural nerve biopsy showed multifocal, interstitial, perivascular, and intramural inflammatory infiltrates. At least one of the areas sampled contained necrotizing inflammatory and thrombosing 44 CHRONIC FIG. 1. T2- weighted ( TR = 3,500/ TE = 85) brain magnetic resonance image at the level of the mid pons. An area of heterogeneous high signal abnormality is noticed in the centromedial aspect of the mid pons. More superior images showed a similar but smaller and discrete lesion at the level of the right medial longitudinal fasciculus. vasculitis, involving medium and small arteries. Findings were histologically consistent with a periarteritis nodosa type of vasculitis. The patient's medication was switched to trian-tene and high- dose i. v. methylprednisolone was begun, but no clinical improvement was seen. She then had multiple courses of plasmapheresis for 2 weeks and was begun on cyclophosphamide. Her symptoms and signs improved slowly, and 18 months after the onset of vasculitis, she continues to have occasional diplopia and a right INO. There has been modest improvement in her neuropathy. COMMENTS Necrotizing vasculitis has been described as resulting from D- penicillamine therapy ( 1- 4). Our patient had central and peripheral nervous system vasculitic manifestations. Her fluctuating INO may have occurred as a result of vasculitic inflammation or demyelination inflammation along the medial longitudinal fasciculus. D- penicillamine- associated vasculitis may occur late in the course of treatment. Donnelly and colleagues reported a patient who developed lupus serology and immune- mediated glomerulonephritis 4 years after beginning D- penicillamine treatment ( 5). OPHTHALMOPLEGIA 45 FIG. 2. T2- weighted ( TR = 3,500/ TE = 85) brain magnetic resonance imaging demonstrating an increase in signal at the level of the right basal ganglia, right internal capsule, and the right periatrial area. Although a rcintroduction of D- penicillamine treatment may have precipitated vasculitis, our patient's symptoms began before the initial drug interruption. Neurological symptoms, such as early diplopia, a manifestation of incipient INO, and oscillop-sia, should alert the clinician of the dangers of reintroducing treatment. Other complications of D- penicillamine therapy include glomerulonephritis, Churg- Strauss syndrome, a myasthenic syndrome, polymyositis, and a lupus- like syndrome ( 6- 8). Paradoxically, penicillamine, along with corticosteroids, has been employed as a form of treatment in rheumatoid arthritis with vasculitis ( 9). Vasculitis should be suspected in patients on D- penicillamine who develop ophthalmoplegia. A myasthenic syndrome should also be considered. Such patients should have discontinuation of treatment. Immunosuppressive therapy and plasma exchange may be appropriate. REFERENCES 1. Curran JJ, Mcdof ME. Necrotizing vasculitis in association with D- penicillamine therapy: report of a case [ Letter]. J Rheumatol 1983; 10: 344- 7. 2. Thorvaldsen J. Penicillamine- induced lupus- like reaction in rheumatoid arthritis and vasculitis. Dermatologica 1981 ; I62: 277- 80. 3. Abe C, Koyama A, Nishimura T. Interleukin- 2 induction, response and therapy on murine lupus lesions in the MRL/ I strain. Prog Clin Biol Res 1987; 229: 147- 56. 4. Bacon PA. Drug therapy and circulating immune complexes in rheumatoid arthritis. Rheumatol Rehahil 1978: 53- 8. J Neuro- Ophthalmol, Vol. 17, No. I. 1997 46 M. PLESS AND T. SANDSON 5. Donnelly S, Levison DA, Doyle DV. Systemic lupus erythe-matosus- like syndrome with focal proliferative glomerulonephritis during D- penicillamine therapy. Br J Rheumatol 1993; 32: 251- 3. 6. Kalina P, Piochazkova L, Hauftova D. | A syndrome similar to systemic lupus erythematosus caused by penicillamine in patients with Wilson's disease]. Bratisl Lek Listy 1985; 84: 336- 40. 7. Stockmann G. | The status of Churg- Strauss syndrome among other hypereosinophilic, granulomatous and vascu-litic diseases]. Z Rheumatol 1988; 47: 388- 96. 8. Jaffe IA. The treatment of rheumatoid arthritis and necrotizing vasculitis with penicillamine. Arthritis Rheum 1970; 13: 436- 43. 9. Stratton MA. Drug- induced systemic lupus erythematosus. Clin Pharmacol 1985; 4: 657- 63. J Nemo- Ophthalmol. Vol. 17, No. I. 1997 |
