Journal of Neuro-Ophthalmology, September 1995, Volume 15, Issue 3

Ocular Motor Systems

journal of Neuro- Ophllitilmotog}/ 15( 3): 191- 201, 1995. (& 1995 Lippincott- Raven Publishers, Philadelphia Annual Review Ocular Motor Systems Part 2: Nuclear and Supranuclear Systems Barry Skarf, Ph. D., M. D. This review covers selected articles dealing with the physiology of eye movements and their disor­ders. The articles appeared in the world medical and scientific literature during 1993. The subject matter and the review are divided into two parts. Part 1, which appeared in a previous issue of this journal, reviewed those articles concerned with in­tranuclear systems. Part 2, presented here, re­views those articles that deal with brainstem and cerebral processes mediating supranuclear and nu­clear control of eye movements. BRAINSTEM Nuclear Palsies Physiological and anatomical evidence has dem­onstrated that the abducens nucleus contains in-terneurons that project to the contralateral medial rectus subnucleus and that localized lesions of the abducens nucleus result in an ipsilateral gaze palsy. Hirose and co- workers presented a clinical/ neuro- radiological correlation of this phenomenon ( 1). Their patient developed an acute left gaze palsy and a partial left internuclear ophthalmople­gia ( INO; actually, an incomplete one- and- a- half syndrome, although they did not point this out) along with left lower motor neuron facial weak­ness. Magnetic resonance imaging ( MRI) demon­strated a discrete lesion in the left pons involving the abducens nucleus, medial longitudinal fascic- Manuscript received April 14, 1995. From the Neuro- ophthalmology Unit, Henry Ford Health Sci­ences Center, Detroit, Michigan, U. S. A. Address correspondence and reprint requests to Dr. B. Skarf, Neuro- ophthalmology Unit, Henry Ford Health Sciences Cen­ter, 2799 West Grand Boulevard, Detroit, Ml 48202, U. S. A. ulus ( MLF), and genu of the seventh nerve, spar­ing the paramedian pontine reticular formation ( PPRF). Acute, isolated cranial nerve palsies in vasculo-pathic patients are usually considered to be due to microvascular infarction along the affected nerve. A collection of seven cases of isolated or predom­inant ocular motor palsies due to brainstem stroke features five patients with oculomotor palsies, one superior oblique, and one abducens palsy ( 2). In each case, the clinical findings are well correlated with the neuroradiological findings. Function tended to improve within a few months. In most cases, there were other signs of a brainstem lesion, such as decreased supraduction of the contralater­al eye ( in three of the five oculomotor palsies) or trigeminal sensory loss. Such findings should raise the suspicion of brainstem stroke and lead to ap­propriate diagnostic investigations, including brainstem MRI. Truly isolated brainstem ocular motor palsies that cannot be distinguished from peripheral nerve lesions are rare. Some controversy exists concerning the extent to which eye movements are affected in amyotrophic lateral sclerosis ( ALS). In a recent article, Gizzi et al. ( 3) reported that ocular motor function is spared in ALS and that ALS patients who have significant eye- movement abnormalities must have additional pathology, such as Parkinson's disease, affecting other systems. These findings were disputed in the correspondence that followed ( 4,5). Taking a different approach to understanding ophthal­moplegia in ALS, Okamoto et al. ( 6) examined third and fourth nerve motor nuclei in 27 patients with ALS using histological and immunohistolog-ical techniques. In all cases, ocular motor neurons were relatively well preserved. In 11 of the 27 ALS patients, there were some rare but definite mor­phological changes similar to those in the anterior 191 192 B. SKARF horns. The abnormalities were more frequent in those patients who also had dementia and were seen in all three patients who had ophthalmople­gia. The authors concluded that by the terminal stage of ALS, the third and fourth motor nuclei can be slightly affected in a manner similar to that of the anterior horns, but that in most cases, the de­gree is less than required for the development of ophthalmoplegia. They concluded that the major­ity of abnormal eye movements seen in ALS are supranuclear in origin. A number of single- case reports described syn­dromes involving nuclear and intranuclear brain­stem loci. A patient seen with " divergence paral­ysis" who was found initially to have a concomi­tant esotropia at distance, progressed to show clear evidence of bilateral abducens and unilateral facial palsies ( 7). The patient also developed uni­lateral gaze- evoked nystagmus. All studies were negative except for increased cerebrospinal fluid ( CSF) protein, which returned to normal when the clinical findings resolved, prompting the authors to make a presumed diagnosis of incomplete Miller- Fisher syndrome. Another unusual case of Miller- Fisher syn­drome, requiring endotracheal intubation for 1 month, was described in a 2- year- old boy who ini­tially was seen with left esotropia ( 8). The child progressed to develop complete external and inter­nal ophthalmoplegia associated with limb ataxia and hyporeflexia and then developed a flaccid, areflexic quadriparesis over 3 days. The patient ap­peared to respond to treatment with plasmapher­esis and immunoglobulin therapy, but full recov­ery took place over several months. Ali findings were attributed to a severe polyradiculoparhy. No evidence of a central process was found, but MRI was not performed. An article in Polish reviewed the pathological mechanism and clinical aspects of Fisher syndrome, and concluded that both periph­eral and central structures are probably involved ( 9). One- and- a- half syndrome was described in a 45- year- old man with allergic granulomatosis and an­giitis { AGA) who was in remission on maintenance prednisolone ( 10). Ocular findings improved on cyclophosphamide and increased prednisolone. Microangiopathy due to the AGA was thought to be the cause of the one- and- a- half syndrome, and its development suggests that long- term treatment with prednisolone and cyclophosphamide along with close monitoring of symptoms and peripheral blood eosinophilia might be indicated in severe AGA. Another patient was described who developed one- and- a- half syndrome after surgery to resect a cavernous angioma from the floor of his fourth ventricle ( 11). This case was reported because the patient also described hallucinations after surgery, but these disappeared while the one- and- a- half syndrome persisted. Mobius syndrome consists of facial diplegia and bilateral horizontal gaze palsies, with convergence used for cross- fixation by some patients. It can be associated with a diverse spectrum of develop­mental anomalies, such as deafness and supranu-merary digits, and with a wide variety of inheri­tance patterns. An infant was described with Mo­bius syndrome and Poland syndrome, cleft palate, dextrocardia, mandibular hypoplasia, and multi­ple areas of diffuse brain- volume loss associated with a t( l; ll)( p22; pl3) translocation ( 12). Because the translocation was present in his phenotypically normal father and brother, it may be coincidental or it may indicate the possibility of genetic hetero­geneity for the Mobius disorder. A constellation of congenital ocular motor defi­cits is described in a patient with bifacial diplegia, right- sided ptosis, complete lack of vertical and ro­tatory movements, large esotropia with defective adduction, bilateral optic disc colobomas, and a retinal detachment in the right eye ( 13). She devel­oped simultaneous bilateral abduction with Bell's phenomenon ( i. e., both eyes abducted on forced eye closure). MRI scan demonstrated the fifth, sev­enth, and eighth nerves but failed to reveal the third nerve. The authors concluded that this pa­tient has congenital defects involving bilateral sec­ond, third, fourth, and seventh nerves. Although the patient had evidence of bilateral abducens function, the authors maintained that their patient falls within the spectrum of Mobius syndrome. Whereas it is clear to this reviewer that the patient has a syndrome involving congenital cranial nerve palsies, her findings suggest a variant of bilateral synergistic divergence, a congenital condition in which there is defective adduction associated with bilateral abduction on attempted gaze to either side, or, alternatively, a variant of Duane's syn­drome. Internuclear Ophthalmoplegia ( INO) An electrooculogram ( EOG) study of 18 patients ( 14) with INO demonstrated that the occurrence, in the abducting eye, of overshoot dysmetria and dissociated nystagmus was often concomitant and related to the degree of interocular dissociation in saccadic velocities as measured by the Versions] Disconjugacy Index ( VDI) = ( peak velocity of ad- } Neitrv- Ophihiilwol, Vol. 15, No. 3, 1995 ANNUAL REVIEW- EYE MOVEMENTS: 2 m ducting eye)/( peak velocity of adducting eye). Thus overshoot amplitude was found to be quan­titatively correlated to the seventy of adduction slowing. The authors concluded that the abduction abnonnalities seen in INO are an expression of adaptive mechanisms that occur in this disorder. Head trauma is an unusual cause of INO, al­though INO after severe brainstem concussion has been described ( 14a). A case of traumatic bilateral INO was described in an 18- year- old man who was in a traffic accident and suffered occipital skull fracture, subdural and subarachnoid hemor­rhages, and transient loss of consciousness ( 15). His condition gradually resolved with conservative management. A more unusual case of isolated, bi­lateral INO after minor head trauma was reported in a 6- year- old boy who fell and hit his occiput hard enough to produce a hematoma but no frac­ture ( 16). There were no other neurologic findings, and CT, MRI, EEG, and CSF studies were nega­tive. The clinical findings were unambiguous, and the patient was monitored longitudinally using EOGs. Diplopia resolved by day 4, but the evi­dence of unilateral INO was present at 6 months and had resolved by 1 year. The authors specu­lated that shear forces within the brainstem pro­duced by head injury may stretch the MLF, caus­ing nerve fiber damage ( 16). A more plausible ex­planation may be that the trauma resulted in focal brainstem ischemia affecting the MLF. The combination of unilateral INO associated with an ipsilateral Horner's syndrome was ob­served in an 84- year- old patient with giant cell ar­teritis ( 17). Another patient, 57 years old, devel­oped bilateral INO, ataxia, and tremor from a focal infarction in the paramedian midbrain tegmentum ( 18). The authors suggested that the lesion could involve the MLF bilaterally and the decussation of the superior cerebellar peduncle, which would re­sult in bilateral INO and ataxia, respectively. Five weeks later, the patient developed a coarse, rhyth­mic, bilaterally symmetrical rubral tremor of the head and limbs, which was attributed to combined involvement of the nigrostriatal pathway and the myoclonic triangle. Premotor ( Supranuclear) Brainstem Lesions Several articles describing thalamic- midbrain le­sions appeared this year, whereas relatively few articles dealt with lesions in the pons. Lesions at both brainstem levels were found in a 22- year- old man with migraine, who developed sudden onset of a pupil- sparing third nerve palsy, hemiparesis, and paraesthesia around the corner of the mouth and in the thumb and index finger on his left side ( 19). MRI showed infarcts in the midbrain tegmen­tum bilaterally and in the right pons, which were attributed to basilar artery migraine. There were no lesions in the cerebral or cerebellar hemi­spheres. The ophthalmoplegia resolved within 12 h, and all symptoms disappeared within 10 days. Basilar artery migraine is a most unusual cause for an infarction in this region. Two cases of selective downgaze palsy with dis­crete bilateral lesions in the region of the rostral interstitial nucleus of the MLF ( riMLF) demon­strated by MRI were described by Green et al. ( 20). One patient was a 9- year- old girl who developed a bilateral midbrain- thalamic infarction after severe pneumococcal meningitis, whereas the second, a 64- year- old man, suffered a midbrain stroke with well- demarcated bilateral lesions just rostral to the red nuclei and anterolateral to the cerebral aque­duct. In both cases, the infarctions were in the ter­ritory of the posterior thalamic paramedian artery, a branch of the basilar communicating artery. This article supported the considerable body of experi­mental and pathological data that assign control of downgaze to both rostral interstitial nuclei of the MLF and that require bilateral lesions of the riMLF to produce selective downgaze palsies. The au­thors pointed out that both patients also had mild slowing of upgaze saccades and concluded that ar­eas critical for upgaze lie just dorsal to the riMLF and are rarely spared completely with bilateral midbrain lesions ( 20). Thalamic- midbrain lesions can cause other ocu­lar motor mischief: Galetta et al. ( 21) described a 48- year- old man who developed a right third nerve palsy and contralateral paralysis of supraduction with eyelid retraction, MRI demonstrated an in­farct in the region of the nucleus of the posterior commissure ( NPC) and third nerve fasciculus. The patient also had left fifth, sixth, seventh, and eighth cranial nerve palsies due to a lesion in the left pons. He also had dysarthria, decreased gag, tongue protrusion to the left, left flaccid hemipa­resis, hemisensory loss, hyperreflexia, and plantar extensor response. Unilateral lesions of the NPC have been implicated in the development of bilat­eral lid retraction ( 22). The ipsilateral third nerve palsy masked the lid retraction that presumably would be present in the right eye, resulting in this " plus- minus" lid syndrome ( 23). The left supra­duction deficit is presumably due to involvement of the right third nerve nucleus or to a lesion in the midbrain producing an upgaze palsy. Although midbrain lesions clearly can cause ver­tical gaze palsies, similar vertical gaze deficits have / Nenro- Opl » l « il » > ol, Vtil. 15, No. 3, 1995 194 B. SKARF been erroneously attributed to exclusively thalamic lesions. Siatkowski et ai. ( 24) argued convincingly that, in these cases, thalamic lesions ( usually in­farctions) must coexist with midbrain pathology, and it is the midbrain lesion that is directly respon­sible for the ocular motor disturbance. This conclu­sion is based on the fact that both thalamus and mesencephalon share a common blood supply and that reports describing the localization of respon­sible lesions to the thalamus have always been based on CT scans, which cannot adequately dis­tinguish lesions of the upper midbrain from tha­lamic lesions. The true extent of these lesions can be demonstrated only with MR1 of the mesenceph­alon, which is recommended in all patients with vertical gaze dysfunction. As if to emphasize this point, four cases of " dor­sal midbrain syndrome" due to unilateral vascular lesions of the posterior medial thalamus and mid­brain were presented in another study ( 25). How­ever, the pretectal area and posterior commissure were involved in all cases. Supporting the diagno­sis, each patient had vertical gaze paresis, conver­gence- retraction nystagmus ( documented by EOG), lid retraction, and pupillary abnormalities. However, in two of the cases, the gaze deficit was for downward movements only, and conver­gence- retraction nystagmus was evoked only with attempted downgaze or convergence. The authors did not explain how patients with lesions of the posterior commissure were spared upgaze palsies. AH four patients improved with time. Rarely, upward- gaze palsy can be a sign of transtentorial upward herniation due to a large cerebellar infarction. A 63- year- old man with mas­sive left cerebellar infarction was seen with ver­tigo, headache, and upgaze palsy; he also had right ptosis, left facial weakness, left- sided hearing loss, and ataxia of the left upper and lower extrem­ities ( 26). He proceeded to lose consciousness over a few hours but improved after decompression of the posterior fossa. The authors pointed out that upward- gaze palsy can be an initial sign of massive cerebellar infarction that, in this setting, must be considered an indication for urgent surgical de­compression. Saad and Sanders described a most unusual pa­tient with loss of infraduction in one eye and of supraductiort in the other ( 27), They found an ar­teriovenous malformation in the rostral midbrain and claimed that this rare ocular motor abnormal­ity should be attributed to interruption of supra­nuclear pathways for vertical gaze and not to a subnuclear lesion of the oculomotor nerve nuclear complex. In a brief review article, Imai et al. ( 28) described the clinical spectrum and differentiating features of Do pa- unresponsive pure akinesia or freezing. This condition bears some similarity to parkinsonism but is different in that marked akinesia or freezing occurs without rigidity or tremor, and it is com­pletely unresponsive to treatment with L- Dopa. The freezing symptoms affect gait, writing, and speech, and there is no dementia. One third of patients have apraxia of eyelid opening, and other ocular motor signs were usually present, including vertical- gaze palsy, convergence palsy, horizontal-gaze nystagmus, square- wave jerks, saccadic pur­suit, and ocular flutter. Vertical optokinetic nystag­mus ( OKN), especially downward, was markedly decreased in all cases. Several patients were either diagnosed as or suspected of having progressive supranuclear palsy ( PSP). Autopsy reports are available on only three patients, also diagnosed clinically as having PSP. Two had pallidonigroluy-sian atrophy ( PNLA), whereas the third had PSP. The authors noted the clinical similarity of these two conditions. They concluded that Dopa-unresponsive pure akinesia is closely related to the " PSP group" of syndromes including PSP, atypical PSP, forme fruste of PSP, and PNLA, but clearly more information is required to define these rela­tionships and the underlying pathology. Two articles ( 29,30) appeared this year dealing with benign paroxysmal tonic upgaze of childhood with ataxia. This benign, self- limited condition is characterized by bouts of tonic upward deviation of the eyes associated with ataxia in infants and young children ( 31). There is no actual ophthal­moplegia, and the patients make downward sac­cadic movements to compensate for the conju­gated upward deviation of their eyes. During the episodes of tonic upward deviation, which occur daily, the patients are unsteady with ataxia and frequent falls. All laboratory, neuroradiological, and neuropathologies ( one case) studies have been normal. Three patients were described ( 29) who had definite family histories of this condition, suggesting that there is an autosomal dominant mode of inheritance, at least in some families. This was not mentioned in any of the previously re­ported cases. These three patients also had motor clumsiness between episodes and delayed acquisi­tion of independent gait. Two of the cases showed improvement when treated with levodopa and car-bidopa, and the authors recommended a therapeu­tic trial in all patients with this condition. Another single case of this condition was reported in a 9- month- old boy who also had cystic fibrosis ( 30). Moving down the brainstem, two new cases of ) Nemo- Of> ltfM » wl, Vol. 15, No. 3, 1995 ANNUAL REVIEW- EYE MOVEMENTS: 2 195 paretic (" unilateral") ocular bobbing were de­scribed ( 32). Movement of the fellow eye was lim­ited to intorsion. In each case, autopsy confirmed the coexistence of a pontine tegmental infarction with a lesion of the third nerve fascicule. The mod­ified bobbing pattern is explained by a unilateral third nerve palsy and an intact fourth nerve at the side of the intorting eye. The neuroanatomic substrate responsible for al­ternating skew deviation on lateral gaze was ex­plored in seven children with brain tumors who had this finding ( 33). In each instance, the ad-ducted eye was hypotropic. Neuroimaging studies showed all seven children had neoplastic involve­ment at the cervicomedullary junction or in the cerebellum or both. The authors argued that other articles on alternating skew that localized the caus­ative lesion to the midbrain pretectum predomi­nantly studied patients with diseases that are not easily localized, such as multiple sclerosis ( MS), trauma, or drug toxicity. They do not, however, mention how many patients with midbrain tumors were reviewed for this study. They believed that their tumor patients had more precise and, there­fore, more accurate topographic locations of the lesions responsible for their skew deviations. Be­cause alternating skew on lateral gaze resembles bilateral superior oblique overaction, the authors speculated that these two conditions may have similar neuroanatomic substrates, especially in pa­tients with known brainstem disease, such as my­elomeningocele, which also includes cerebellar and cervicomedullary region abnormalities. The ocular tilt reaction ( OTR) is the clinical triad of head tilt, conjugate ocular torsion, and skew deviation produced by damage to the utricle and its brainstem projections. Although animal and human studies indicate that the labyrinth, lateral vestibular nucleus, and interstitial nucleus of Cajal all contribute to the OTR, most reported cases have involved brainstem lesions [ for an exception, see Halmagyi et al. ( 34)]. It is of interest, therefore, that two recent articles described the development of OTR after vestibular neurectomy or labyrinthec-tomy or both to treat acoustic neuroma or Me­niere's disease ( 35,36). Four patients, reported by Wolfe and co- workers ( 35), experienced vertical diplopia after this surgery, and their double vision prompted neuro- ophthalmological consultation. These authors emphasized that diplopia may be the only symptom in patients with OTR. In all four cases, diplopia resolved within 3 months. In con­trast, Vibert et al. ( 36), who described a single pa­tient, argued that OTR caused by peripheral nerve lesions is probably underrecognized because the diplopia and other subjective components are masked by oscillopsia and nystagmus resulting from vestibular neurectomy. The evanescent na­ture of the vertical and cyclotorsional deviations produced by peripheral lesions make their pres­ence hard to recognize. In the case described, dip­lopia and skew deviation resolved within a few days, but conjugate eye cyclotorsion lasted weeks ( 36). In the same theme, monocular and binocular oc­ular torsion and tilt in subjective visual vertical were studied in 111 patients with either acute vas­cular brainstem lesions or MS. Measures were compared with those observed in 110 normal con­trols ( 37). Of 86 patients, 83% exhibited patholog­ical ocular torsion of one ( 47%) or both ( 36%) eyes. Of 111 patients, 94% showed a pathological tilt of the subjective visual vertical. Most patients recov­ered gradually over 1 month. All unilateral brain­stem lesions caudal to the upper pons were found to cause ipsiversive ocular torsion of one or both eyes, with concurrent ipsiversive tilts of the sub­jective visual vertical. All lesions rostral to this pontine level produced contraversive tilts in both measures. This finding supports the concept that ascending projections from the vestibular nuclei to the interstitial nucleus of Cajal decussate in the pons or caudal midbrain ( 35). For those who can read German, an extensive and well- illustrated review of basic physiology and disorders of the vestibulo- ocular reflex, optokinetic nystagmus, and smooth pursuit eye movements is available ( 38). Cerebellar Lesions Cerebellar infarction is relatively uncommon, representing - 1.5% of strokes. A clinical and ra­diological review of 66 patients with cerebellar in­farcts revealed that lesions in the posterior inferior cerebellar artery ( PICA), and superior cerebellar artery ( SCA) distributions have distinct differences in clinical presentation, course, and prognosis ( 39). Infarcts in the PICA distribution are seen with ver­tigo, headache, and gait imbalance and had a ten­dency to be life threatening because of brainstem compression from postinfarct swelling. Patients with SCA infarcts had gait and limb ataxia at onset with much less vertigo and headache and gener­ally had a benign clinical course. Of interest to neuro- ophthalmologists, 75% of patients with PICA infarcts had nystagmus, whereas only 50% of patients with SCA infarcts had nystagmus. In both groups, the nystagmus was predominantly hori­zontal and beat either ipsilaterally or bilaterally. ; Nmro- Ofiltfliatinot, Vol. 15, Mi. 3, 1995 196 B. SKARF Fewer than 6% of the patients in each group man­ifested horizontal contralateral nystagmus exclu­sively. Of PICA infarcts, 11%, and 7% of SCA in­farcts were associated with vertical nystagmus. The authors pointed out that no elements in the bedside analysis of the nystagmus allowed a dis­tinction to be made between the two vascular ter­ritories. In particular, they noted that vertical up-beating nystagmus, thought to be associated with vermian lesions, was not a feature of SCA cases, although those cases frequently involved the su­perior vermis. In concluding, this article empha­sized the importance of monitoring brainstem signs during the early stages of cerebellar swelling. The onset of ipsilateral sixth nerve palsy or hori­zontal gaze palsy is likely to indicate direct lateral pontine compression as a result of postinfarction cerebellar swelling, requiring emergency posterior fossa decompression ( 39). In a single case, ocular flutter- like oscillations occurring on refixation were observed and re­corded with EOG for the first time in a patient with a chronic history of human T- cell lymphoma virus type I ( HTLV- I)- associated myelopathy ( 40). A benign, presumably autosomal dominant, vestibulocerebellar disorder with prominent ocular motor abnormalities, seen in early childhood ( but not congenitally), was described in 10 family mem­bers ( 41). Impairment or absence of smooth pur­suit and vestibulo- ocular reflex ( VOR) suppression associated with gaze- evoked and rebound nystag­mus, slow build- up of OKN, mildly hyperactive VOR, and a high incidence of strabismus were noted in affected individuals. Most patients were asymptomatic, except for strabismus, and the con­dition was remarkable for the absence of other cer­ebellar signs. CEREBRAL HEMISPHERES Eye movements were recorded in 10 individuals who developed conjugate eye deviation ( CED) af­ter hemispheric stroke ( 42). These patients were part of a larger group of 74 cases of CED who were observed clinically. All 74 patients had at least some difficulty making saccadic and smooth pur­suit movements in the contralateral direction. Re­covery of clinically evident CED occurred in all pa­tients who survived. The duration of the recovery period varied between 1 and 65 days. Some pa­tients with prolonged recovery periods had preex­isting lesions of the contralateral hemisphere, and generally the responsible lesions in these patients were larger than the lesions of the entire group. Eye movement were recorded serially for 6 months after recovery of CED. These studies demonstrated that contralateral saccades had prolonged latencies and hypometric amplitudes and that ipsilateral saccades also had slightly prolonged latencies, compared to controls. After recovery of CED, smooth pursuit movements were disturbed to both sides but were generally worse in the ipsilateral direction. Subtle abnormalities were still present at 6 months in most patients. Based on the observa­tions that during CED, smooth pursuit movements are more limited in a contralateral direction but that after the disappearance of CED, there was asym­metry symmetry of smooth pursuit in the ipsilateral direction, the authors postulated that during CED, a spatial defect must predominate, prohibiting contralateral smooth pursuits. To support this, they noted that nearly all patients with CED show one or more manifestations of neglect. They con­cluded that the pattern of abnormal eye move­ments seen in their patients implies an important influence from the parietal lobe and from hemis-patial neglect ( 42). A selective contralateral saccadic palsy associ­ated with contralateral supranuclear facio-palatopharyngeal paresis resulted from a small he­matoma in the corona radiata adjacent to the genu of the internal capsule ( 43). On CT, the lesion was only 7 mm in diameter. This correlation suggests that the descending pathway from the frontal eye field in humans may pass through the genu along with the corticobulbar tract. An infant born at 27 weeks of gestation was eval­uated at 5 months of age with electro- oculography and VEPs when he was noted to be visually unre­sponsive ( 44). Smooth pursuit and OKN could be elicited only with movement of the target or sur­round to the left. In contrast, saccades were sym­metrical in both directions. This finding, coupled with an asymmetrical occipital distribution of the flash and pattern VEPs, strongly suggested a right-sided posterior hemispheric lesion involving the occipital and parietal areas. A large hemispheric cyst was confirmed on imaging studies. The au­thors pointed out the usefulness of noninvasive techniques in neuro- ophthalmological investiga­tions of preverbal children and infants. To evaluate the lateralizing significance of head and eye deviation associated with seizures, 29 pa­tients were studied with generalized tonio- clonic seizures that had a clearly defined lateralized focus ( 45). The traditional dictum that head- or eye-turning is produced by an irritating lesion in the contralateral hemisphere, was found in > 90% of seizures, but only when the movement occurred within 10 s of generalization or continued as the ; Neuto- Ophlhaluiot, Vol. " 15, No. 3, 1935 ANNUAL REVIEW- EYE MOVEMENTS: 2 197 seizure generalized. In contrast, the direction of the deviation was ipsilateral in more than 90% of seizures when the movement ended more than 10 s before the seizure began to generalize. Oculogyric crisis and retrocollis are described in a 50- year- old man with bilateral putaminal hemor­rhages ( 46), supporting the association between fo­cal dystonia and bilateral lesions of the putamen. NYSTAGMUS Congenital Nystagmus Persons with congenital nystagmus ( CN) rarely experience oscillopsia. To investigate whether ex-traretinal signals ( efference copy and propriocep­tion) can contribute to the cancellation of retinal image motion produced during CN, Bedell and Currie tested four subjects by having them point in the perceived direction of targets that were flashed for 2 ms in total darkness ( 47). The pointing errors made by the subjects varied systematically accord­ing to the phase of the nystagmus waveform dur­ing which the target was presented, but were only 25% of the amplitude that would be expected if there were no extraretinal signals available. There­fore, the authors concluded that extraretinal sig­nals can compensate for 75% of the changes in eye position that occur during the nystagmus cycle and that they may play a role in preventing oscil­lopsia. Retinal image motion is increased in patients with nystagmus, and whereas it frequently de­grades visual acuity, it also tends to degrade ac­commodative function ( 48). Patients with CN were found to exhibit marked variability in their accom­modative function and abnormal depth of focus. There was no significant difference in accommoda­tive function between albinotic or idiopathic groups of CN patients. In another study, however, there was a differ­ence between the VEPs recorded from the single albino member of a family with idiopathic CN and other family members ( 49). Only the albino patient exhibited the contralateral VEP asymmetry, which is a marker for the visual fiber misrouting charac­teristic of albinos. Conversely, then, idiopathic CN cannot be attributed to the same structural or func­tional abnormality in retinostriate projections evinced by the contralateral asymmetry in the VEP seen in albinos. Horizontal jerk nystagmus recorded using EOG from a single patient with oculocutaneous albinism was noted to reverse in direction when the patient was exposed to any extraneous light stimulation ( 50). The authors speculated that this phenome­non is probably related to sensory pathway abnor­mality found in albinism. Idiopathic congenital motor nystagmus may have a variety of different etiologies and, if inher­ited, may show X- iinked, autosomal dominant or recessive inheritance. A family with autosomal dominant CN and no significant loss of visual function was described in which the nystagmus cosegregates with a balanced 7; 15 translocation, suggesting a possible localization for autosomal dominant CN ( 51). Two affected members of the family who were examined demonstrated horizon­tal nystagmus with a small rotatory component. The presence of a null zone of nystagmus and a dampening of nystagmus with convergence are two features of CN that can be exploited surgically to give better visual acuity and to alleviate anom­alous head posture. Preoperative and postopera­tive binocular visual acuities and eye- movement recordings were compared in 18 patients with CN with head turn who underwent eye muscle sur­gery consisting of the Anderson- Kestenbaum pro­cedure ( seven patients) or the artificial divergence procedure ( six) or both ( five) ( 52). In all three groups, the null zone shifted toward the primary position. EOGs demonstrated a broadening of the null zone in the artificial divergence and combined groups, with only a modest enlargement in the Anderson- Kestenbaum group. There was also in­crease in foveation time for three of the patients in the artificial divergence group and for two patients in the combined group. One of six patients in the artificial divergence group and four of five in the combined treatment group had improvement in binocular visual acuity of two or more Snellen lines, and this can be attributed to increased fove­ation times. The authors recommended the artifi­cial divergence procedure for all patients with CN and head turn with good binocular function and suggested using a combined procedure if fusional convergence is not capable of fully alleviating the head turn. They reserved the Anderson- Kes­tenbaum procedure for patients with poor binocu­lar fusion. Kommerell and Zee described two patients with esotropia and typical latent nystagmus who were able to release and suppress their nystagmus at will, when neither eye was occluded ( 53). The nystagmus evoked always beat toward the ambly­opic eye but could be as strong as that which de­veloped when the amblyopic eye was occluded. The authors speculated that these patients exerted voluntary control on their nystagmus by varying the suppression of visual input from their ambly- / Ncvro- Ophtliiiliiiol, Vol. 15, No. Z, ' 1395 198 B. SKARF opic eye at will; the more they suppressed one eye, the greater the release of nystagmus. A review of nystagmus in childhood, including CN, latent, and acquired forms appeared as part of a larger survey of pediatric neuro- ophthalmologic disease ( 54). Acquired Nystagmus Two patients with acquired pendular nystagmus and oscillopsia were shown to obtain relief of their symptoms with improved visual acuity after alco­hol ingestion ( 55). One patient had MS with brain­stem and cerebellar involvement. The second pa­tient had developmental anomalies and congenital severe myopia; pendular nystagmus was noted to increase gradually as his retinal function deterio­rated with progressive retinal disease ( detach­ment, hemorrhage, and degeneration). No other drugs were found that could mimic the beneficial effect of alcohol. The authors speculated that ac­quired pendular nystagmus might arise from deaf-ferentation of the inferior olive, either from lack of visual input or from structural interruption of af­ferent pathways or both. Another study of 37 patients with pendular nystagmus and optic neuropathy due to MS sup­ports the view that afferent visual input to brain­stem centers may play an important role in the generation of acquired pendular nystagmus ( 56). In 18 patients with dissociated nystagmus, the side with larger oscillations was always the one with evidence of the more severe optic neuropathy, when optic neuropathy was also asymmetric. In contrast, asymmetries in 1NO or cerebellar signs did not correlate with the side of nystagmus asym­metry. Because of this finding, it was suggested that the dissociation in pendular nystagmus might be due to the asymmetries in the optic neuropathy rather than to asymmetries in cerebellar or brain­stem disease. In this study, all 37 patients also had cerebellar eye signs and other ocuiar motor abnor­malities, including INO ( 24) saccadic dysmetria ( 15), macrosaccadic oscillations ( six) and ocular flutter ( one), gaze- evoked nystagmus ( 26), re­bound nystagmus ( four), convergence- evoked up­beat lid nystagmus ( two), and convergence-evoked upbeat ocular nystagmus ( four). The MRI findings were also of interest: seven of eight pa­tients who underwent MRI had cerebellar or brain­stem lesions, and the most consistent finding was a lesion in the dorsal pontine tegmentum ( 56). Vegetative state is a clinical condition resulting from serious organic brain damage, characterized by " unaware wakefulness," typically alternating with sleep stages that can be indistinguishable from those occurring in normals ( 57). Spontaneous CNS nystagmus in six vegetative- state patients was documented across the sleep- wake cycle ( 58). During stage 1 of sleep, nystagmus decreased to between 37.5 and 75% of the amplitude observed in the " awake" state. Nystagmus was abolished in stage 2 and in slow- wave sleep, but episodes of nystagmus were observed during rapid eye move­ment ( REM) sleep in all patients. The clinical sig­nificance of these findings is unclear because, in this limited sample, there appears to be no rela­tionship between nystagmus density during REM sleep and patient outcome. A mother and daughter with familial congenital cerebellar ataxia were found to have periodic alter­nating nystagmus ( PAN; 59). The responses of both patients to vestibular stimulation with rota­tory and caloric tests were studied, disclosing en­hanced VORs, changes in direction, and prolonga­tion of the cycles of PAN. A number of single- case reports described dif­ferent types of nystagmus developing as a conse­quence of a variety of neurological lesions. In­verted Bruns' nystagmus ( coarse nystagmus to the side opposite the lesion, fine nystagmus to the same side as the lesion) was noted in a 9- year- old girl after a shunting procedure to drain two large arachnoid cysts at the cerebellopontine angle ( 60). It is suggested that the Bruns' nystagmus in this case was caused by asymmetrical function within the vestibular nuclei or flocculus or both, A 49- year- old woman who was seen with acute onset of vertigo and spontaneous horizontal-rotatory nystagmus to the left was diagnosed with MS ( 61). Abnormalities in the left- sided auditory brainstem responses were demonstrated 2 days before the patient progressed to develop total hearing loss and persisted for at least 10 months, although hearing returned to normal by 10 weeks. Downbeating nystagmus should always suggest a diagnosis of Chiari malformation and requires MRI of the posterior fossa. Two single case reports of patients with Arnold- Chiari malformation doc­ument other etiologies that contributed to the de­velopment of nystagmus and oscillopsia in these patients ( 62,63). The first case report described the development of horizontal- torsional nystagmus with oscillopsia in a previously asymptomatic woman with Arnold- Chiari malformation 2 weeks after lumbar puncture ( 62). The nystagmus almost disappeared by 3 months after decompressive sur­gery. The authors cautioned that lumbar puncture may accentuate craniospinal pressure dissociation and precipitate neurological signs in patients with f Neitro- Ophlhabnol, Vol. 15. No. 3, 1995 ANNUAL REVIEW- EYE MOVEMENTS: 2 199 Arnold- Chiari malformation and also pointed out that horizontal or torsional nystagmus ( or both) can be a feature of this condition. Another patient with Arnold- Chiari malformation developed lith­ium- induced downbeat nystagmus and oscillopsia 1 year after starting the drug ( 63). The nystagmus resolved spontaneously when lithium was discon­tinued, and surgical decompression was not re­quired. Although lithium toxicity can cause down-beating nystagmus on its own, the authors specu­lated that toxicity may have had an additive effect when combined with the mechanical compression resulting from the Arnold- Chiari malformation, and they advised neuroimaging of all patients with downbeating nystagmus, even when the nystag­mus seems to be temporally related to the intro­duction of lithium therapy. A patient with intermittent, reproducible down­beat nystagmus that developed when he turned his head to his left side was described ( 64). The episodes were attributed to transient occlusion of a dominant vertebral artery by an osteophyte at C- 6 and were relieved with surgical removal of this osteophyte. Keane ( 65) described a group of 14 patients with cysticercosis ( from among his series of 224 cases) who exhibited severe and unusual ocular motor disturbances, including upbeat nystagmus, PAN, bilateral fourth nerve palsies, and oculopalatal my­oclonus. Although the presence of papilledema and pretectal signs ( in 78 and 134 patients, respec­tively) is much more common in cysticercosis, this diagnosis should be considered in all patients from areas in which it is endemic who have evidence of posterior fossa disease. GENERALIZED NEUROLOGIC AND SYSTEMIC DISEASES A number of articles described different charac­teristics of ocular motor function in patients with a variety of neurological conditions, such as MS. An oculographic study of reflex horizontal saccades in 65 patients with MS and in 50 normal subjects demonstrated that the saccadic duration to small-angle saccades was more sensitive than saccadic velocity or latency in detecting clinical and subclin­ical ocular motor abnormalities ( 66). Creutzfeldt- Jakob disease ( QD) typically is seen with subacute dementia; abnormalities of eye movements are not usually prominent, except in a small group of patients who have a " cerebellar form," Three patients were described who were seen, early in the course of their disease, with ab­normal eye movements that included PAN and slow vertical saccades ( 67). Gradually, all saccades and quick phases of nystagmus were lost, but pe­riodic alternating gaze deviation persisted. At au­topsy, two of the three patients had pronounced involvement of the cerebellum, especially of the midline structures. The patients who lost saccades also had involvement of the saccade- generating re­gions in the pons and midbrain. The authors ad­vised that QD should be considered in patients with subacute progressive neurological disease, even when dementia is overshadowed by ataxia and oculomotor finding ( particularly PAN). Eye movements were evaluated in 53 insulin-dependent diabetics and compared to those of 42 nondiabetic controls ( 68). Saccades made by dia­betics had longer reaction times and decreased ac­curacy when compared to normals. Maximum pur­suit velocities were also reduced at all target veloc­ities in diabetic patients. An extensive historical and scientific review of eye- movement abnormalities in schizophrenics ap­peared in German ( 69). Disorders of smooth pur­suit and saccadic systems were described, illus­trated, and copiously referenced. A prospective study of 70 patients in their first episode of schizo­phrenia examined smooth pursuit eye move­ments, among other parameters, and found that 51% of patients had eye- tracking dysfunction ( 70). The rate in this sample of patients with first-episode disease is consistent with the prevalence in other samples of acutely ill, chronic, and remit­ted schizophrenics. Because these abnormalities appear early in the course of the disease, before treatment with neuroleptics in most cases, the au­thors concluded that the abnormalities are a con­sequence of the disease rather than the effects of chronicity, drug treatment, or institutionalization. Opsoclonus- myoclonus ( OM) syndrome is a paraneoplastic condition most frequently associ­ated with neuroblastoma in children. Case reports that appeared this year provided the first descrip­tion of a patient with Hodgkin's disease who de­veloped severe opsoclonus and myoclonic move­ments of the head and limbs 7 weeks after she was treated with high dose BEAM chemotherapy ( BCNU, etoposide, cytarabine, melphalan; 71). At that time, she still had a persistent mediastinal mass, which was treated with localized radiother­apy. She also received i. v. methylprednisolone, and her symptoms gradually resolved. The au­thors discounted the possible role of the cytotoxics in producing this clinical picture, because this ef­fect has not been reported and because 8 weeks elapsed between the last course of treatment and the onset of neurological symptoms. } Ncuro- Oytithatmtf, Vol. 15, No. .1, 1995 200 B. SKARF A 21- month- old child was described with OM of unknown etiology ( 72). Extensive investigation was negative, but this child initially responded to prednisolone but later relapsed. The authors pointed out that in this case, treatment with hu­man immunoglobulin ( Sandoglobulin) failed to benefit the patient. After 9 months, a course of prednisolone combined with low- dose azathio-prine resulted in significant improvement. Ste­roids were tapered after 4 weeks, but the azathio-prine was maintained with continued good effect. Adrenocorticotropic hormone ( ACTH) can also be used in the treatment of OM. Some OM pa­tients, however, may develop antibodies to exog­enous ACTH ( 73). This may explain the loss of efficacy of ACTH with chronic use in this syn­drome. It is suggested that antibodies to ACTH should be sought in patients with OM who fail an ACTH trial, exhibit tolerance to ACTH, or who have undergone prolonged ACTH treatment. The article also pointed out that direct assays of ACTH may not measure ACTH that is bound to antibody and that an indirect assay of ACTH may be re­quired to uncover true serum levels. A patient with an occult malignant lymphoma of the brain had findings suggestive of OM ( 74). She had a lesion in the left dentate nucleus, which ini­tially responded to oral prenisolone. When she re­lapsed, brain biopsy disclosed the true diagnosis, and she was treated with radiation therapy with subsequent disappearance of her opsoclonus, my­oclonus, and ataxia. REFERENCES 1. Hirose G, Furui K, Yoshioka A, Sakai K. Unilateral conju­gate gaze palsy due to a lesion of the abducens nucleus. Clinical and neuroradiological correlations. ] Clin Ncuro Ophthalmol 1993; 13: 54- 8. 2. Kim JS, Kang JK, Lee SA, Lee MC, Isolated or predominant ocular motor nerve palsy as a manifestation of brainstem stroke. Stroke 1993; 24: 581- 6. 3. Gizzi M, DiRocco A, Sivak M, Cohen B. Ocular motor func­tion jn motor neuron disease. Neurology 1992; 43: 1037- 46. 4. Okuda B. ALS and eye movements. Neurology 1993; 43: 4- 51. 5. Norris FH. ALS and eye movements. Neurology I993; 43: 450- 1. 6. Oka mo to K, Hirai 5, Amari M, et al. Oculomotor nuclear pathology in amyotrophic lateral sclerosis. Acta Neuropalhol 1993; 85: 458- 62. 7. Friling R, Yassur Y, Merkin L, Herishanu YO. Divergence paralysis versus bilateral sixth nerve palsy in an incomplete Miller- Fisher syndrome. Neuro- ophthalinology 1993; 13: 215- 17. 8. Eggenberger ER, Coker S, Menezes M. Pediatric Miller- - Fisher syndrome requiring intubation: a case report. Clin Pediatr 1993; 32: 372- 5. 9. Azcaepanska- Szerej A. Pathogenetic and clinical aspects of Fisher syndrome. Neurol Neurochir Pol 1993; 27: 239- 46, 10. Amano A, Miyagi K, Sakata M, et al. Allergic granuloma­tosis and angiitis associated with intestinal perforation and eye movement disorder. Ryumacni 1993; 33: 255- 9. 11. FujiiT, Park C, Koide K, Uno E, Tsuchiya Y. Appearance of hallucinations and one- and- a- half syndrome after resection of a cavernous angioma located in the fourth ventricle floor. Mo Skmkei Geka 1993; 21: 157- 61, 12. Donahue SP, Wenger SL, Steele MW, Gorin MB. Broad-spectrum Mobius syndrome associated with a 1; 11 chromo­some translocation. Arch Neurol 1993; 50: 799- 802. 13. Tusscher MPMT, Houtman AC, Oostenbrugge RJV, Wil-mink ) T. Oculofacial paralysis with simultaneous bilateral abduction in Bell's phenomenon and bilateral disc colobo-mas. Neurophthalmology 1993; 13: 297- 302. 14. Getenet JC, Ventre ], Vighetto A, Tadary B. Saccades in internuclear ophthalmoplegia; are abduction disorders re­lated to interocular disconjugacy? / Neurol Sci 1993; 114; 160- 4. 14a, Keane JR. Traumatic internuclear ophthalmoplegia. ] Clin Neuro Ophthalmol 1987; 7: 1162- 5. 15. Kuroiwa T, Tanabe H, Takatsuka H, et a). Traumatic bilat­eral MLF svndrome- a case report. No To Shinkei I993; 45: 377- 80. 16. Mueller C, Koch S, Toifl K. Transient bilateral internuclear ophthalmoplegia after minor head trauma. Dev Med Child Neurol 1993; 35: 163- 6, 17. Askari A, ( olobe OM, Shepherd DI. Internuclear ophthal­moplegia and Horner's syndrome due to presumed giant cell arteritis. / R Soc Med 1993; 86: 362. 18. Okuda B, Tachibana H, Sugita M, Maeda Y. Bilateral inter­nuclear ophthalmoplegia, ataxia, and tremor from a mid­brain infarction. Stroke 1993; 24: 481- 2. 19. Yasuda Y, Matsuda I, Namura S, Morita T. Ophthalmople­gia, hemiparesis and cheiro- oral syndrome in basilar artery migraine. Eur Neurol 1993; 33: 185- 7. 20. Green JP, Newman N), Winterkorn JS. Paralysis of down-gaze in two patients with clinical- radiologic correlation. Arch Ophthalmol 1993; 111: 219- 22, 21. Galetta SL, Gray LG, Raps EC, Grossman RI, Schatz NJ, Unilateral ptosis and contralateral eyelid retraction from a thalamic- midbrain infarction. Magnetic resonance imaging correlation, f Clin Ncuro Ophthalmol 1993; 13: 22H, 22. SchmidtkeK, Biittner- Ennever JA. Nervous control o/ eye­lid function: a review of clinical, experimental and patho­logical data. Brain 1992; 115: 227- 47. 23. Gaymrd B, Lafitte C, Gelot A, de Toffol B. Plus- minus lid syndrome. / Neurol Neurosurg Psychiatry 1992; 30: 128- 31. 24. Siatkowski RM, Schata NJ, Sellitti TP, Galetta SL, Glaser JS, Do thalamic lesions really cause vertical gaze palsies? / Clin Neuro Ophthalmol 1993; 13: 190- 3. 25. Albera R, Magnano M, Lacilla M, Luda E, Sicuro L, de Lucchi R. Vascular dorsal midbrain syndrome. Clinical and oculography findings in four cases. Neuro- ophlhalmology 1993; 13: 207- 13. 26. Yamazaki M, Hashimoto T, Haruta S, Yanagisawa N. A case of transtentorial upward herniation due to cerebellar infarction manifesting upward gaze palsy as an initial sign. No To Shinkei 1993; 454: 183- 7. 27. Saad N, Sanders MD. Midbrain angioma with disconjugate vertical gaze palsy, Aust NZ ] Ophthalmol 1993; 21,123- 6, 28. Imai H, Nakamura T, Kondo T, Narabayashi H, Dopa-unresponsive pure akinesia or freezing. A condition within a wide spectrum of PSP? Adv Neuro! 1993; 60: 622- 5. 29. Campistol], Prats JM, Garaizar C. Benign paroxysmal tonic upgaze of childhood with ataxia. A neuro- oph-thalmological syndrome of familial origin? Dev Med Child Neurol 1993; 35: 436- 9. 30. Gieron MA, Korthals JK. Benign paroxysmal tonic upward gaze. Pcdiatr Neurol 1993; 9: 159. 31. Ouvrier RA, Billson F, Benign paroxysmal tonic upgaze of childhood, | Child Neurol 1988; 3: 177- 80. 32. Dehaene I, Lammens M, Marchau M, Paretic ocular bob­bing. A clinicopathological study of two cases. Neuro­phthalmology 1993; 13: 143- 6. / Nettro- Ofiltliwlitiui, Vol. 15. No. J, 1995 ANNUAL REVIEW- EYE MOVEMENTS: 2 201 33. Harried LM, Maria BL, Quisling RG, Mickle JP, Alternating skew on lateral gaze. Neuroanatomic pathway and rela­tionship to superior oblique overaction. Ophthalmology 1993; 100: 281- 6. 34. Halmagi GM, Gresty MA, Gibson WPR. Ocular tilt reaction with peripheral vestibular lesion. Ann Neurol 1979; 6: 80- 3. 35. Wolfe Gl, Taylor CL, Flamm ES, Gray LG, Raps EC, Galetta SL. Ocular tilt reaction resulting from vestibuloacoustic nerve surgery. Neurosurgery 1993; 32: 417- 20, 36. Viberl D, Safran AB, Hausler R. Clinical evaluation of oto­lithic function by the measurement of ocular cyclotorsion and skew deviation. Ann Otolaryngol Chir Ccrvkofac 1993; 110: 87- 91. 37. Dieterich M, Brandt T. Ocular torsion and tilt ot subjective visual vertical are sensitive brainstem signs. Ann Neurol 1993; 33: 292- 9. 38. Mehdorn E, Supranuclear ocular motility disorders. II, Dis­orders of the vestibulo- ocular reflex, optokinetic nystagmus and pursuit movements. Opthalmology 1993: 90: 296- 312. 39. Kase CS, Norrving B, Levine SR, et a). Cerebellar infarc­tion. Clinical and anatomic observations in 66 cases. Stroke 1993; 24: 76- 83. 40. Iwanaga K, Mori K. A case of HTLV- I associated myelop­athy with flutter- like oscillation, Rinsho Shiiikeigaku 1993; 33: 83- 5. 41. Harris CM, Walker], Shawkat F, Wilson], Russell- Eggitt I. Eye movements in a familial vestibulocerebellar disorder. Neu roped ia tries 1993; 24: 117- 22, 42. Tijssen CC, van Gisbergen JAM. Conjugate eye deviation after hemispheric stroke. A contralateral saccadic palsy? Neuro- ophthalmolog\ f 1993; 13: 107- 18. 43. Fukutake T, Hirayama K, Sakakibara R. Contralateral se­lective saccadic palsy after a small haematoma in the corona radiata adjacent to the genu of the internal capsule. ] Neurol Neurosurg Psychiatry 1993; 56: 221. 44. Jacobs M, Shawkat F, Harris CM, Kriss A, Taylor D. Eye movement and electrophysiological findings in an infant with hemispheric pathology. Dev Med Chilli Neurol 1993; 35: 431- 5. 45. Kernan JC, Devinsky O, Luciano DJ, Vazquez, B, Perrine K. Lateralizing significance of head and eye deviation in sec­ondary generalized tonic- clonic seizures. Neurology 1993; 43: 1308- 10. 46. Shimpo T, Fuse S, Yoshizawa A, Retrocollis and oculogyric crisis in association with bilateral putaminal hemorrhages. Rinsho Shiiikeigaku 1993; 33: 40- 4. 47. Bedell HE, Currie DC, Extraretinal signals for congenital nystagmus. Invest Ophthalmol Vis Sei 1993; 34: 2325- 32. 48. Ong E, Ciuffreda KJ, Tannen B. Static accommodation in congenital nystagmus. Invest Ophthalmol Vis Set 1993; 34: 194- 204. 49. Shallo- Hoffman (, Apkarian P. Visual evoked response asymmetry only in the albino member of a family with congenital nystagmus. Invest Ophthalmol Vis Sei 1993; 34: 682- 9. 50. Choi YC, Kim SK, Lee SH, Lee MS, Choi IS, Chung UK, Eye movement changes in albinism- a case report with electronystagmographic findings. Yonsei Med j 1993; 34: 195- 200. 51. Patton MA, Jeffery S, Lee N, Hogg C. Congenital nystag­mus cosegregating with a balanced 7; 15 translocation. / Med Genet 1993; 30: 526- 8. 52. Aubcov AA, Stark N, Weber A, Wizov SS, Reinecke RD, Improvement of visual acuity after surgery for nystagmus. Ophthalmology 1993; 100: 1488- 97, 53. Kommerell G, Zee DS. Latent nystagmus. Release and sup­pression at will. Invest Ophthalmol Vis Sei 1993; 34: 1785- 92. 54. Repka MX. Common pediatric neuro- ophthalmologic con­ditions. Pediatr Clin North Am 1993; 40: 777- 88. 55. Mossman SS, Bronstein AM, Rudge P, Gresty MA. Ac­quired pendular nystagmus suppressed by alcohol. Neur­ophthalmology 1993; 13: 99- 106. 56. Barton JJ, Cox TA. Acquired pendular nystagmus in mul­tiple sclerosis: clinical observations and the role of optic neuropathy. / Neurol Neurosurg Psychiatry 1993; 56: 262- 7. 57. Jennett B, Plum F. Persistent vegetative state after brain damage, lancet 1972; 1: 734- 7. 58. Gordon CR, Oksenberg A. Spontaneous nystagmus across the sleep- wake cycle in vegetative state patients. Eieetroen-cephahgr Clin Neurophysiol 1993; 86: 132- 7. 59. Sakakibara R, Hirayama K, Takaya Y, Shinoto H, Hat tori T. Periodic alternating nystagmus in familial congenital cere­bellar ataxia. Rinsho Shiiikeigaku 1993; 33: 1- 7. 60. YokotaJ, ImaiH, Okuda O, SatoK. Inverted Brun's nystag­mus in arachnoid cysts of the cerebellopontine angle, Eur Neurol 1993; 33: 62- 4. 61. Gstoettner S, Swoboda H, Muller C, Burian M. Preclinical detection of initial vestibulocochlear abnormalities in a pa­tient with multiple sclerosis. Eur Arch Otorhinoltnyngol 1993; 250: 40- 3. 62. Barton JJ, Sharpe JA, Oscillopsia and horizontal nystagmus with accelerating slow phases following lumbar puncture in the Arnold- Chiari malformation. Ann Neurol 1993; 33: 418- 21, 63. Monteiro MLR, Sampaio CM. Lithium- induced downbeat nystagmus in a patient with Arnold- Chiari malformation. Am ! Ophthalmol 1993; 116: 648- 9. 64. Rosengart A, Hedges TR 10, Teal PA, et at. Intermittent downbeat nystagmus due to vertebral artery compression. Neurology 1993; 43: 216- 18. 65. Keane JR. Cysticercosis: unusual neuro- ophthalmic signs. / Clin Neuro Ophthalmol 1993; 13: 194- 9. 66. Gibson JM, Ritouret I, Collins AD. Reflex horizontal sac-cades in multiple sclerosis. A clinically robust quantitative approach, Neuro- ophlhalmology 1993; 13: 289- 96. 67. Grant MP, Cohen M, Petersen RB, et al. Abnormal eye movements in Creutzfeldt- jakob disease. Ann Neurol 1993; 34: 192- 7. 68. Virtaniemi J, Laakso M, Nuutinen J, Karjalainen S, Vartiainen E. Voluntary eye movement tests in patients with insulin- dependent diabetes mellitus. Acta Otolaryngol 1993; 113: 123- 7. 69. Arolt V, Steege D, Nolte A. Disorders of eye movements in schizophrenia.- a critical review and future perspectives. Fortschr Neurol Psychiatr 1993; 61: 90- 105. 70. Lieberman JA, Jody D, Alvir JM, et al. Brain morphology, dopamine, and eye- tracking abnormalities in first- episode schizophrenia. Prevalence and clinical correlates. Arch Gen Psychiatry 1993; 50: 357- 68. 71. Kay CL,' Davjes- Joiies GA, Singal R, Winfield DA. Parane­oplastic opsoclonus- myoclonus in Hodgkins's disease. / Neurol Neurosurg Psychiatry 1993; 56: 831- 2. 72. Penaien JM, Speck S, Vassella F. Opsoclonus polymyoclo-nia syndrome. Acta Paedialr 1993; 82: 319- 20. 73. Pranzatelli MR, Kao PC, Tate ED, et al. Antibodies to ACTH in opsoclonus- myoclonus. Neuropediatrics 1993; 24: 131- 3, 74. Tsuzaka K, Aimoto Y, Minami N, Moriwaka F, Tashiro K. A case of primary intracranial malignant lymphoma pre­senting opsoclonus- myoclonia syndrome, Rinsho Shiiikeigaku 1993; 33: 194- 8. j NaiivOphtlmlmd, Vol. 15, No. .3, 1.995