Journal of Neuro-Ophthalmology, June 1986, Volume 6, Issue 2

Periodic alternating nystagmus associated with albinism.

We examined a 73-year-old woman with the rare association of albinism and (presumably) congenital periodic alternating nystagmus. The mechanism of the nystagmus in this case is uncertain. Anomalous retinogeniculate pathways have been documented in albino animals. Periodic alternating nystagmus might occur in some patients with albinism if there are also anomalies in the pathways conveying visual information to the cerebellum and brainstem.

«) 1986 Raven Press, New York Periodic Alternating Nystagmus Associated with Albinism David R. Guyer, M.D., and Simmons Lessell, M.D. We examined a 73-year-old woman with the rare associ­ation of albinism and (presumably) congenital periodic alternating nystagmus. The mechanism of the nys­tagmus in this case is uncertain. Anomalous retinoge­niculate pathways have been documented in albino an­imals. Periodic alternating nystagmus might occur in some patients with albinism if there are also anomalies in the pathways conveying visual information to the cer­ebellum and brainstem. Key Words: Albinism- Periodic alternating nystagmus. From the [k'partml'nt of Ophthalmology, Harvard Medical School. and thl' Massachusetts Eye and Ear Infirmary, Boston, Massachusetts. Address correspondence and reprint requests to Dr. Simmons Lessell. 243 Charles St., Boston, MA 02114, U.S.A. 82 Periodic alternating nystagmus (PAN) is a hori­zontal or horizontal-torsional jerk-nystagmus in which cyclic changes occur in both direction and velocity. Several pathologic (1-4) and eye move­ment recording studies (5-11) suggest that PAN may be caused by lesions at the vestibular com­missure and in the pathways that convey visual information to the caudal brainstem and cere­bellum (10,12). PAN has been associated with vestibulocere­bellar diseases (1,3-5,11,13-30) and with loss of vision (6,9,13,15,30,31). Congenital cases also have been described (5,6,8,24,30,32), one of which was associated with albinism (6). We report a second case of (presumably) congenital PAN asso­ciated with albinism. CASE REPORT A 73-year-old, right-handed woman was re­ferred because of visual loss. The patient and her sister, who always had had nystagmus and ex­tremely fair skin and hair, were evaluated medi­cally in childhood and told that they were "on the border of albinism." The patient's visual acuity always had been subnormal, but had been suffi­cient for her to read and she was not considered visually handicapped. The details of ophthalmic and medical examinations performed early in her life are unavailable. She alleged that she had pain­less progressive visual impairment in both eyes for 1 year, uncorrectible by lenses. The patient's past medical history was otherwise unremarkable and she was not taking medications. Examination showed an intelligent, cooperative albino woman with a normal neurological exami­nation. Best-correctible visual acuities were 16/100 in each eye. She had normal color vision with Ishi­hara's plates. Visual fields could be tested only by confrontation because of nystagmus, but no defect PAN ASSOCIATED WITH ALBINISM 83 was evident. Both irides transilluminated. She had nuclear sclerosis of both lenses, not dense enough to explain her visual impairment. Pupillary eXilmi­nation was unremarkable. She had coarse, hori­zontal nystagmus which on horizontill gilze to ei­ther side beat in the direction of gaze; however, in the primary position, the direction of the fast phase alternated. Each interval was YO s, with a brief pendular "intermission." There was no ver­tical nystagmus. The patient illso had a small, con­comitant left exotropia. Dilated fundus eXilmina­tion showed an albinotic fundus, but no other ab­normalities. It was difficult to evaluate the maculas because of the adventitious eye move­ments. DISCUSSION In PAN, each cycle usually lasts 60-360 s, with a 4- to 20-s neutral interval (6-8,10,13,33). The amplitude slowly increases over 1 min ar.d then decreases slowly until the neutral period is reached (33). Cross et al. (13) divided cases of PAN among three categories: cases with vestibulocerebellar disease, cases with loss of vision, and congenital cases. Neurological disorders that have been asso­ciated with PAN include Arnold Chiari type 1 malformation (8,11,30), cerebellar degeneration secondary to alcohol and phenytoin (14), cere­bellar cyst (5), vertebrobasilar ischemic disease (15,30), neurosyphilis (1,5,6,16,17), brainstem as­trocytoma (4), toruloma of the floor of the fourth ventricle (19), perinatal hypoxia (8), arachnoid cyst compressing the cerebellum and medulla (2), Frie­dreich's ataxia (18), chronic otitis media (16,20­22), encephalitis (5,6), multiple sclerosis (3.5,8,25), tumor of the corpus callosum (20,22-24), basilar skull fracture (5,22,27-29), acoustic neurinoma (30), and following surgery for a cerebellar tumor (30). The second category consists of patients in which loss of vision is the predominant abnor­mality. PAN may occur in blind patients (6,13), in the darkness only (9), or only with the eyes closed (15,30). If the vision is restored [such as after vit­rectomy for bilateral vitreous hemorrhages (13) or after cataract surgery (31)], the PAN may disap­pear. Patients who develop PAN from loss of vi­sion might be harboring a congenital lesion of the brainstem or cerebellum that is "silent" until there is a reduction in retinal input (13,33). Although our patient's visual impairment was slight com­pared to patients who have been reported as de-veloping PAN after losing vision, it is still possible that her PAN was acquired rather than congenital, the recent decline in vision presumably sufficient to precipitate PAN in a susceptible individual. Un­fortunately, there were no descriptions of her ear­lier eye findings to help settle this issue. Cross et al.'s third group of patients consists of those with congenital PAN (13). In comparison with cases of acquired PAN, these cases have normal hearing and neurological examinations and their nystagmus is augmented by fixation (8,30). While most of these congenital cases are free of other defects (5,6,8,24,30,32), Davis and Smith (6) have described one patient with congen­ital PAN associated with albinism. In an analysis of eye movements in 16 human albinos, Collewijn et al. found two patients with horizontal jerk nys­tagmus that reversed direction spontaneously or with visual stimulation during binocular viewing (34). These cases were not described clinically and there was no regular periodicity to the nystagmus. Our patient appears to be only the second re­ported case of congenital PAN in an albino, but the concurrence of two rare abnormalities in each of two patients indicates that this is unlikely to be a chance association. How might albinism cause PAN? One possi­bility is that the nystagmus is consequent to sub­normal vision. Boylan and Harding (35) have sug­gested that the nystagmus seen in albinos might be the result of poor central fixation from lack of foveal differentiation. Fulton et al. have demon­strated that the fovea as such is absent in albinos (36). However, Collewijn et al. (34) have mar­shalled evidence showing that poor acuity does not cause the nystagmus in human albinos. They point out that albinos first manifest nystagmus ~t an age when normals lack foveal differentiation and that while all albinos lack foveal differentia­tion, some do not have nystagmus. An alternative explanation for the PAN in albinos (and perhaps even for the more common forms of nystagmus encountered in albinos) is that congenital brain anomalies contribute. The existence of anomalous visual pathways in albinos are well documented in the literature. Al­though the view is still controversial, most author­ities believe that the anomalies are related to hy­popigmentation of the retinal pigment epithelium. Several albino mammals (including humans) have been shown to have misrouted retinogeniculate projections (38-40) in which most of the temporal retinal fibers project information to the contralat­eral hemisphere! In the albino cat, fewer than 5% of the temporal retinal ganglion cells project ipsi- I Gill NCllnhll'"t1mlll"'l, Vol. 6. No.2. 1986 8-1 D. R. GUYER AND S. LESSELL laterally (41). Guillery l't al. (40) documented misrouting in a Ilt'llropathological study of a human with oculocutal1l'ous albinism. They found a small wtalt.'d latl'ral gl'niculatl' nuclt'us and ab­normal fusions L1l'twl'l'n the layers of the genicu­late nuclt>us. Abnormal fusions in this area are SUggl'StiW of miswuting. These findings are con­sistent with the rl'sldts of several studil's of the vi­su, ll-evokt'd potenti,ll in albino subjl'cts (3Y,42­44). Boylan ,1Ild Harding (35) have suggested that abnorn~al p,lthways to the midbrain also might playa role in the pathogenesis of nystagmus in albinos. There are several pathways that convey visual information to the brainstem and cerebellum. At least in nonhuman mammals, visual information reaches the cerebellum from the visual cortex (45) and the superior colliculus (46), in both cases via the pons. There also may be contributions from the accessory optic tract through the inferior olive (47,48). Although albino rabbits were used in some of these investigations, there is no informa­tion on the occurrence of such abnormalities in human albinos. Is it possible that some human al­binos have nystagmus on the basis of misrouting of these or other visual inputs to the brainstem or cerebellum? Opticokinetic nystagmus has been studied ex­tensively in albino animals (49,50), and the results of those investigations may provide insight into how misrouted fibers might produce nystagmus. Winterson and Collewijn (51) comment that ocular instability in the albino rabbit (brought out by re­stricting visual stimuli to their nasal fields) is con­sequent to an abnormality in opticokinetic pursuit. In the normal, opticokinetics act as a negative feedback system that stabilizes the eye with re­spect to the surround. The nucleus of the optic tract plays an important role in mediating the opti­cokinetic response in rabbits. In the albino rabbit, anomalous retinal innervation inverts the direc­tional selectivity of those cells in the nucleus of the optic tract that have receptive fields in the nasal visual fields. This inversion in effect creates posi­tive feedback, causing the opticokinetic system to destabilize rather than stabilize the eye. "Once the eye moves, it continues to move" (51). Leigh et al. 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