Journal of Neuro-Ophthalmology, March 2001, Volume 21, Issue 1

A Girl Without a Chiasm

An otherwise healthy 15-year-old girl with a congenital nystagmus was evaluated at our department using visual evoked potential recording and magnetic resonance imaging. She appears to have the unique isolated inborn absence of the optic chiasm, described only once before in two unrelated girls. Unlike these previously described cases, our patient does not seem to display a see-saw nystagmus.

Journal of'A] euro- Ophthalmology 21( 1): 26- 29, 2001. © 2001 Lippincott Williams & Wilkins, Inc., Philadelphia A Girl Without a Chiasm: Electrophysiologic and MRI Evidence for the Absence of Crossing Optic Nerve Fibers in a Girl With a Congenital Nystagmus Nomdo M. Jansonius, MD, PhD, Ton ( A) M. van der Vliet, MD, Frans W. Cornelissen, PhD, Jan Willem R. Pott, MD, PhD, and Aart C. Kooijman, PhD An otherwise healthy 15- year- old girl with a congenital nys­tagmus was evaluated at our department using visual evoked potential recording and magnetic resonance imaging. She ap­pears to have the unique isolated inborn absence of the optic chiasm, described only once before in two unrelated girls. Un­like these previously described cases, our patient does not seem to display a see- saw nystagmus. Key Words: Optic chiasm- Congenital nystagmus- See- saw nystagmus- Achiasmatic- Albino. When a nystagmus is recognized shortly after birth, the first concern is the differentiation between a primary congenital nystagmus ( motor defect nystagmus) and a nystagmus secondary to a bilateral afferent defect ( sen­sory defect nystagmus). We present a patient with a con­genital nystagmus, originally classified as a motor defect nystagmus. Fifteen years after birth, the diagnosis had to be reconsidered because of an extremely rare magnetic resonance imaging ( MRI) finding. CASE REPORT An otherwise healthy girl was diagnosed with a con­genital nystagmus 4 months after birth. She did not have any other ocular or neurologic abnormality, and the fam­ily history was negative. The first measurement of visual acuity, at an age of 3 years, yielded values of 20/ 100 OD and 20/ 200 OS. Acuity remained apparently stable in the first decade. A combined myopic astigmatism developed gradually. At the age of 15 years, she returned to our department. Acuity at that time was 20/ 400 OD (- 3.50- 2.00x10°) Manuscript received May 30, 2000; accepted January 3, 2001. From the Department of Ophthalmology ( NMJ, JWRP), Department of Radiology ( AMV), and the Laboratory of Experimental Ophthal­mology ( FWC, ACK) of the University of Groningen, Groningen, the Netherlands. Address correspondence and reprint requests to Dr. Nomdo M. Jansonius, Dept. Ophthalmology, University Hospital Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands; e- mail: n. m. jansonius@ ohk. azg. nl. and less than 1/ 60 OS (- 6.00^. 00x20°). She had not noticed any acuity change herself. She was evaluated along with her 10- year- old sister, who complained of poor vision for the past year. In this girl, acuity measure­ment yielded 20/ 100 OU ( previously documented to be 20/ 20). Both girls performed well in a regular secondary school, the elder with ambulant support of a low- vision rehabilitation service. In both girls, perimetry, electrore-tinogram ( ERG), visual evoked potential ( VEP), exten­sive blood investigations, a neurologic examination, and a MRI were performed in addition to a thorough oph­thalmic examination. In the younger of the two sisters, no abnormalities were found, except for concentrically constricted visual fields. She was diagnosed to have functional visual loss. Currently ( 2 years later), her vi­sual acuity is at least 20/ 25. In the elder sister, ophthalmic examination showed a horizontal nystagmus that remained horizontal in upgaze and downgaze, normal pupillary reactions without a rela­tive afferent defect, no iris transillumination, and a nor­mal fovea and optic nerve head. Fundus examination and photography were hampered by photophobia. No sub­stantial esotropia or exotropia was found. Versions were normal. Prism tests ( base- out prisms for testing the pres­ence of binocular single vision) were inconclusive be­cause of the nystagmus. Perimetry revealed concentrically constricted visual fields, symmetrically around and without any disconti­nuity along the vertical meridian. Figure 1 presents the results. This finding was reproduced at a separate visit. MRI revealed a complete absence of the chiasm: the optic nerves appeared to be headed directly toward the geniculate bodies. There were no signs of a septo- optic dysplasia ( Figs. 2 and 3). This unusual finding has been described only once before ( 1,2). Eye movement registrations performed in primary gaze are shown in Figure 4. As the figure shows, the nystagmus is essentially a horizontal pendular nystagmus with a frequency of approximately 2 to 3 Hz and an amplitude of approximately 10°. Unlike the previously described cases, our patient did not seem to display a see- saw nystagmus. 26 A GIRL WITHOUT A CHIASM 27 FIG. 1. Goldmann perimetry. Only the V4 was seen OS. The V4, III4, and 14 were recorded OD, but, for the sake of clarity, only the V4 is displayed in this figure. Both ERG and VEP were recorded. ERG responses were strictly normal. Pattern VEP did not provide con­sistent recordings. Flash VEP, when tested monocularly, yielded a response after approximately 150 to 200 ms, only in the hemisphere on the side of the stimulated eye. This result is shown in Figure 5. Visual evoked potential asymmetry has been mea­sured ( 1,2) in both patients with albinism ( contralateral response exceeds ipsilateral response) and in achiasmatic patients ( ipsilateral response exceeds contralateral re­sponse). We analyzed our VEP data using a method modified from Ver Hoeve et al. ( unpublished; presented at the 1998 meeting of the American Association for Pediatric Ophthalmology and Strabismus, Palm Springs, CA) and Soong et al. ( 3), who studied misrouting in albinism. In short, a chiasm coefficient is calculated from the differences of the recorded signals from the right and left hemispheres. For details, see Table 1. The chiasm coefficient is a number between - 1 and 1. In case of a FIG. 2. Magnetic resonance image showing axial slices as an inversion recovery sequence ( TR/ TE/ TI 6838/ 60/ 350) with a slice thickness of 4 mm and an interslice gap of 0.4 mm. A: Both optic nerves curve to the lateral side of the suprasellar cistern without crossing over as would have been the case in the presence of a chiasm. B: Both nerves continue their course as the optic tract. normal chiasm, the chiasm coefficient is approximately zero. This result also holds if one optic nerve produces a weaker signal than the contralateral one. If a weaker signal is recorded on one hemisphere lead than on the other, a positive coefficient results. A negative chiasm coefficient is consistent with either > 50% crossing of fibers in the chiasm ( as in albinism) ( 4) or with <^ 50% crossing ( as in an achiasmatic visual system). If noise dominates the recorded signal, the chiasm coefficient will head toward zero. We determined the chiasm coef­ficient 13 times in our patient from measurements ob­tained during two separate visits. Values ranged from - 0.89 to - 0.35. In six subjects with a presumed normal chiasm, we found values ranging from - 0.2 to 0.9. In five albino patients studied, the chiasm coefficient varied between - 1.0 and 0. DISCUSSION In this article, we presented an unusual finding in a 15- year- old girl with a congenital nystagmus. The iso­lated absence of the optic chiasm we found is, to our knowledge, the first independent confirmation of Apkar-ians nondecussating retinal- fugal fiber syndrome, origi­nally described in two unrelated girls ( 1,2). Absence or hypoplasia of the chiasm has been described in patients ( male and female) with several other midline abnormali­ties ( 5). Like the previously published isolated cases, our patient displays a reduced visual acuity OU, a congenital nystagmus, no iris transillumination, and no foveal hy­poplasia. Like the others, she has blue irides and blond hair. Blue eyes and blond hair, however, is the default for girls in the Netherlands, and all three girls are Dutch. Unlike the previous findings ( 1,5), our patient does not seem to show a see- saw nystagmus. It must be noted that when recording such a large horizontal nystagmus, a small vertical nystagmus can easily be overlooked. Also, a small vertical nystagmus that is phase locked with the horizontal nystagmus can easily be induced as an artefact. The apparent presence or J Neuro- Ophthalmol, Vol 21, No. 1, 2001 28 N. M. JANSONIUS ET AL. FIG. 3. Magnetic resonance image showing coronal slices as a T-, W SE sequence ( TR/ TE 532/ 15) with a slice thickness of 5 mm and an interslice gap of 0.5 mm. Both optic nerves ( A) maintain their course beside the infundibular stalk and infundibular recess ( B) to the optic tracts ( C). No sign of an optic chiasm in front of the infundibular stalk is present. absence of a vertical nystagmus depends on the defini­tion of the horizontal plane. Changing the horizontal plane a few degrees makes it possible to observe a con­jugate vertical nystagmus, a disconjugate nystagmus ( SSN), or no vertical nystagmus at all. Because of this we can not exclude that there is some vertical conjugate nystagmus or SSN, but the nystagmus of our patient appears to have at least a remarkably small vertical com­ponent as compared to the previously published data in which the vertical amplitude seems to exceed the hori­zontal amplitude ( 2). In addition to the achiasmatic humans, a congenital absence of the chiasm has been described in Belgian sheepdogs ( 6). The achiasmatic dogs do present a hori­zontal nystagmus, and at least some of them also have a see- saw nystagmus ( 7,8). CD c o ' • ^ CO o Q_ I 20deg OS horizontal OD horizontal Time ( s) FIG. 4. Eye movement recordings. Recordings OD and OS, hori­zontally and vertically, were all performed simultaneously. Eye movements were registered using an EyeLink Gaze tracker ( Sen-soMotoric Instruments, Teltow, Germany). The EyeLink is an in­frared video- based pupil tracker that samples eye position 250 times per second. It is equipped with head position compensa­tion- although this feature was not critical in our experiment, because we used a chinrest. Technically, the EyeLink's spatial resolution is better than 0.1 degrees. Eye- position accuracy with a chinrest, in healthy subjects, is typically approximately 0.5 degrees average error ( measured by calibration- accuracy valida­tion). Because of the large nystagmus in our subject, the Eye- Link's normal automated calibration procedure failed and was replaced by a manual posthoc procedure: the subject had to look at four different positions ( left, right, above, and below the central fixation point), and the signals obtained by this procedure were used to scale the horizontal and vertical eye- movement traces. 50 > Q_ LU > RH- ODH JL 100 200 Time ( ms) 300 400 FIG. 5. Flash VEP recordings. Stimulus is given at t = 0 ms. Offset is set to 5,15, 25, and 35 uV, respectively. Electrode position was 3 cm above and lateral with respect to the inion. Reference elec­trode was at the ipsilateral ear, common at the forehead. RH- OD is the signal recorded from the right hemisphere while stimulating OD; LH- OD the signal from the left hemisphere while stimulating OD; RH- OS the signal from the right hemisphere while stimulat­ing OS; and LH- OS the signal from the left hemisphere while stimulating OS. J Neuro- Ophthalmol, Vol 21, No. 1, 2001 A GIRL WITHOUT A CHIASM 29 TABLE 1. Calculation of the chiasm coefficient To cope with drift and offset, the calculation starts with a high- pass filtering of the recorded signal. This filtering is established by subtract­ing the average of the previous T ms of the recorded signal from the recorded signal: V( t) = VJt) - ( 1/ T) f Vh') dt' where V( i) is the filtered signal and Vr( f) the recorded signal. Calcula­tions were performed with T = 60 ms. Subsequently the chiasm coef­ficient ( cc) is calculated: fVRH, ODW " ^ LH. ODW] • [ VRH, osW " VLH, OSW] dt cc = fj[ yRH, ODM - VLH, ODW] • [ VRH. OSW - VLH, OSW] I dt where VRH- OD is m e signal recorded from the right hemisphere while stimulating OD, VLH- OD m e signal from the left hemisphere while stimulating OD, VRHOS the signal from the right hemisphere while stimulating OS, and VLH- os m e signal from the left hemisphere while stimulating OS. Calculations were performed with tx = 60 ms and t2 = 300 ms; stimulus is given at t = 0 ms. In dogs, achiasmatism has an autosomal recessive mode of inheritance ( 6). In humans, only unrelated cases of achiasmatism have been described. Our patient has an unaffected brother and sister. One of the patients de­scribed by Apkarian ( 2) is a fraternal twin ( both girls) and has an unaffected twin sister and an unaffected older brother and sister. Five normal brothers and sisters does not exclude an autosomal recessive mode of inheritance ( p = 0.29, Poisson distribution with 0 observed and 5/ 4 = 1.25 expected). An autosomal dominant mode of inheritance could be considered less likely because of the absence of either nystagmus or visual impairment in the family history. Three female and no male patients with isolated achiasmatism makes an X- linked mode of inheritance less likely and suggests that achiasmatism affects women more frequently than men. However, this difference is not significant ( p = 0.13, Poisson distribu­tion with 3 observed and 3/ 2 = 1.5 expected). Finally, achiasmatism found at age 15 can be a true agenesis or a secondary degeneration. In our case, perimetry provides a major argument against a degen­eration. A degeneration of the chiasm should yield a bitemporal hemianopsia. Visual fields symmetrically around and without any discontinuity along the vertical meridian, as found in our patient, suggest a true agenesis. Comparable visual fields were found by Apkarian et al. ( 1). REFERENCES 1. Apkarian P, Bour LJ, Barth PG. 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