Ocular Motor Deficits Research Articles

A model-based theory on the origin of downbeat nystagmus

The pathomechanism of downbeat nystagmus (DBN), an ocular motor sign typical for vestibulo-cerebellar lesions, remains unclear. Previous hypotheses conjectured various deficits such as an imbalance of central vertical vestibular or smooth pursuit pathways to be causative for the generation of spontaneous upward drift. However, none of the previous theories explains the full range of ocular motor deficits associated with DBN, i.e., impaired vertical smooth pursuit (SP), gaze evoked nystagmus, and gravity dependence of the upward drift. We propose a new hypothesis, which explains the ocular motor signs of DBN by damage of the inhibitory vertical gaze-velocity sensitive Purkinje cells (PCs) in the cerebellar flocculus (FL). These PCs show spontaneous activity and a physiological asymmetry in that most of them exhibit downward on-directions. Accordingly, a loss of vertical floccular PCs will lead to disinhibition of their brainstem target neurons and, consequently, to spontaneous upward drift, i.e., DBN. Since the FL is involved in generation and control of SP and gaze holding, a single lesion, e.g., damage to vertical floccular PCs, may also explain the associated ocular motor deficits. To test our hypothesis, we developed a computational model of vertical eye movements based on known ocular motor anatomy and physiology, which illustrates how cortical, cerebellar, and brainstem regions interact to generate the range of vertical eye movements seen in healthy subjects. Model simulation of the effect of extensive loss of floccular PCs resulted in ocular motor features typically associated with cerebellar DBN: (1) spontaneous upward drift due to decreased spontaneous PC activity, (2) gaze evoked nystagmus corresponding to failure of the cerebellar loop supporting neural integrator function, (3) asymmetric vertical SP deficit due to low gain and asymmetric attenuation of PC firing, and (4) gravity-dependence of DBN caused by an interaction of otolith-ocular pathways with impaired neural integrator function.

Spectrum of infantile esotropia in primates: Behavior, brains, and orbits

Recent studies of human infants have described a spectrum of early-onset esotropia, from small angle to large heterotropias. We report here a similar spectrum of early-onset esotropia in infant monkeys, with emphasis on the relationship between visuomotor deficits, central nervous system circuitry, and orbital anatomy. Eye movements were recorded in macaque monkeys with natural, infantile-onset esotropia (n = 7) and in control monkeys (n = 2) to assess alignment, latent nystagmus, dissociated vertical deviation (DVD), and pursuit/optokinetic nystagmus (OKN) asymmetries. Acuity was measured by preferential-looking technique or spatial sweep visual-evoked potentials. Geniculo-striate pathways were then analyzed with neuroanatomic tracers and ocular dominance column labels. Extraocular muscles were examined by high-resolution magnetic resonance imaging (MRI) and anatomic sectioning of whole orbits. Esotropia ranged from 4 to 13.5 degrees (7-24(Delta)) with fixation preference (if any) varying idiosyncratically (as in human). Severity of ocular motor dysfunction (ie, nystagmus velocity, DVD amplitude, pursuit-OKN nasal bias index) increased as the magnitude of esotropia angle. Animals with greater ocular motor deficits tended to have greater visual area V1 (striate cortex) neuroanatomic deficits, evident as fewer binocular horizontal connections in V1. Orbital MRI/anatomic analysis showed no difference in horizontal rectus cross-sectional areas, muscle paths, innervation densities, or cytoarchitecture compared with normal animals. The infantile esotropia spectrum in nonhuman primates is remarkably similar to that reported in human infants. Concomitant esotropia in these primates cannot be ascribed to abnormalities of the extraocular muscles or orbit. These findings, combined with epidemiologic studies of humans, suggest that perturbations of cerebral binocular pathways in early development are the primary cause of the infantile esotropia syndrome.

Ocular Manifestations in Korean Patients with Multiple Sclerosis

Objective: The overall influence of race on ocular manifestations in multiple sclerosis (MS) is unknown. Methods: This study reviewed ocular manifestations in Korean MS patients from 1996 to 2004. Results: Of the 121 patients, 62 (51%) showed ocular manifestations that comprised optic neuritis (ON) in 52 (42.9%), ocular motor deficits in 11 (9.1%), and visual field defects in 2 (1.7%). Of the 27 patients (45 eyes) with ON whose medical records were available for results of the ophthalmologic tests, 19 patients (70%) experienced painless visual loss and 8 eyes (17.8%) showed severe disc edema. Twenty-nine of 37 patients (78.4%) with isolated ON as an initial manifestation showed normal brain MRI and twenty-seven (73%) negative oligoclonal band (OCB). Of the ocular motor findings, unilateral internuclear ophthalmoplegia (6 patients) was the most common. Conclusions: Korean MS patients showed lower frequencies of ON and ocular motor deficits than Caucasian and Japanese patients. The known risk factors associated with increased risk of developing MS in several western studies did not apply to Korean ON. Our study suggests that ocular manifestations of MS may differ among the races.

One-and-a-Half Syndrome in Neuromyelitis Optica

The authors describe a rare case of bilateral, sequential optic neuritis and one-and-a-half syndrome, with correlated magnetic resonance imaging of the brain. Intravenous corticosteroid was administrated as treatment of the ocular motor deficit; however, partial resolution and subsequent recurrence of optic neuritis with transverse myelitis were observed. After re-treatment, neurological deficits were remedied, but visual loss remained.

Long-term Outcomes of Pediatric Ocular Myasthenia Gravis

To review the presenting signs, therapeutic interventions, and clinical outcomes of purely ocular myasthenia gravis in a preadolescent population treated primarily with pyridostigmine bromide. Retrospective case series. Twenty-one consecutive patients younger than 12 years with purely ocular myasthenia gravis at initial presentation. The clinical charts were reviewed retrospectively. Time to generalization, stabilization, or resolution; prism cover test results; and visual acuity. Median age at onset was 26 months. The mean duration of follow-up was 6.5 years (range, 2-15). Presenting signs included ptosis (95%), strabismus (76%), limitation of ductions (17%), and Cogan's lid twitch (76%). The most common form of strabismus was exotropia. Pyridostigmine monotherapy was the initial treatment for all patients. Corticosteroids were added to the therapy for 6 patients. Generalization to systemic disease occurred in 3 patients. Two of those required intravenous immunoglobulin and thymectomy. Complete resolution off of medical therapy occurred in 4 patients. All patients had stabilization of the ocular motor deficits regardless of treatment. Eleven patients were treated for amblyopia; 2 had residual amblyopia. Ocular myasthenia in preadolescent children generally presents before age 5 and is clinically distinguished from the disease as it affects adults. Although the presenting signs of strabismus, ptosis, and Cogan's lid twitch are common in children or adults, the response to treatment and eventual outcomes differ. Most children can be safely treated with pyridostigmine alone. Generalization to systemic disease occurs at a much lower rate than in adults. Ocular manifestations stabilize in all children and completely resolve in some.

Gaze Control and Foot Kinematics During Stair Climbing: Characteristics Leading to Fall Risk in Progressive Supranuclear Palsy

Does gaze control influence lower-extremity motor coordination in people with neurological deficits? The purpose of this study was to determine whether foot kinematics during stair climbing are influenced by gaze shifts prior to stair step initiation. Twelve subjects with gaze palsy (mild versus severe) secondary to progressive supranuclear palsy were evaluated during a stair-climbing task in a cross-sectional study of mechanisms influencing eye-foot coordination. Infrared oculography and electromagnetic tracking sensors measured eye and foot kinematics, respectively. The primary outcome measures were vertical gaze fixation scores, foot lift asymmetries, and sagittal-plane foot trajectories. The subjects with severe gaze palsy had significantly lower lag foot lift relative to lead foot lift than those with a mild form of gaze palsy. The lag foot trajectory for the subjects with severe gaze palsy tended to be low, with a heading toward contact with the edge of the stair. with severe gaze palsy were 28 times more likely to experience "fixation intrusion" (high vertical gaze fixation score) during an attempted shift of gaze downward than those with mild ocular motor deficits (odds ratio [OR]=28.3, 95% confidence interval [CI]=6.4-124.8). Subjects with severe gaze shift deficits also were 4 times more likely to have lower lag foot lift with respect to lead foot lift than those with mild ocular motor dysfunction (OR=4.0, 95% CI=1.7-9.7). The small number of subjects and the variation in symptom profiles make the generalization of findings preliminary. Deficits in gaze control may influence stepping behaviors and increase the risk of trips or falls during stair climbing. Neural and kinematic hypotheses are discussed as possible contributing mechanisms.

Migrainous Vertigo: Clinical, Oculographic and Posturographic Findings

Migrainous vertigo (MV) is accepted as a common cause of episodic vertigo. The peripheral or central vestibular localization of the deficit as well as the pathophysiology is unclear. This prospective study was designed to assess the clinical features of MV and to search for the localization of the vestibular pathology. Thirty-five patients with MV, 20 patients with migraine and 20 healthy volunteers were studied. Comprehensive neurotological tests were performed between attacks. None of the normal controls or the patients with migraine had ocular motor deficits or caloric test abnormalities. Three patients in the MV group showed saccadic pursuit (8.6%), in one of whom saccadic hypometria was also present. Caloric test results revealed unilateral caloric hypofunction in seven patients (20%). Static posturography results revealed increased sway velocity when the eyes were closed or the platform was distorted in patients with MV. These findings during the symptom-free period revealed that peripheral vestibular dysfunction was more common than a central deficit.

Evidence for Ocular Motor Deficits in Developmental Dyslexia: Application of the Double-Step Paradigm

Dyslexia is a language-based learning disability characterized by difficulties with reading, spelling, and writing. Persons with dyslexia often have deficits in processing rapid temporal sensory information. There is also evidence of sensorimotor deficits in persons with dyslexia. Whether these deficits include ocular motor problems is still an open question. Some previous studies have shown an increased saccadic latency in dyslexics, whereas others have not reproduced this finding. The purpose of the present study was to investigate saccadic latency in young adults with dyslexia during the double-step paradigm, a task that requires rapid sequential visual information processing and saccade generation. The study hypothesis was that dyslexics have a longer saccadic latency in the second orthogonal saccade, a task that nondyslexics parallel process and perform rapidly. Eight students with dyslexia and eight age-matched control subjects participated in the study. Their eye movements were monitored with the scleral search coil technique in simple saccade trials and in the double-step paradigm. The second saccade was either orthogonal or colinear to the first. Intersaccadic interval and latency were calculated for the second saccade. No difference in saccadic latency was found for colinear second saccades; however, dyslexics had significantly longer latencies for orthogonal second saccades. This included a subset of subjects who had longer latencies for orthogonal than for colinear saccades. The findings indicate that under certain conditions, when the demand for rapid visual information processing is high and a rapid saccade sequence is required, some persons with dyslexia show ocular motor deficits manifested by longer saccadic latencies.

Depth perception in cerebellar and basal ganglia disease

There is increasing evidence that the cerebellum and the basal ganglia serve not only a role in motor control but also in visual perception. Patients with Parkinson's disease (PD) as well as patients with cerebellar lesions exhibit impairments of vision that are not fully explained by ocular motor deficits. It is less clear to which extent these visual deficits contribute to an impaired control of visually guided movements. This study examined whether a dysfunction of the cerebellum or the basal ganglia induces impairments in depth perception, which affect action. We employed an illusionary display, the Ames trapezoidal window, to determine the ability of PD patients (n=10) and patients with spinocerebellar ataxia (SCA) (n=6) to process depth cues when estimating object slant. Participants either pointed to the edges of the window (motor judgement) or verbally indicated the perceived orientation of the display (verbal judgement). To control for ocular and limb motor deficits, participants judged the slant of a non-illusionary display in a second task. Slant estimation of the non-illusionary window was not impaired in either patient group when compared to control subjects (all P>0.2). In contrast, SCA as well as PD patients exhibited significantly greater slant estimation errors than controls when pointing to the illusionary window (P=0.005). In addition, both patient groups made larger errors than controls in their verbal judgements during binocular viewing of the illusion (P=0.005), but not during monocular viewing (P>0.2). In sum, the present findings point towards a role for both the basal ganglia and cerebellum for the processing of visual information about depth. Since the deficits were seen both in the context of action and perception and were only partially reconciled by the availability of binocular depth cues, we conclude that basal ganglia as well as cerebellar disease may affect the visual perception of depth.

Eye Movements of the Murine P/Q Calcium Channel Mutant Tottering, and the Impact of Aging

Mice carrying mutations of the gene encoding the ion pore of the P/Q calcium channel (Cacna1a) are an instance in which cerebellar dysfunction may be attributable to altered electrophysiology and thus provide an opportunity to study how neuronal intrinsic properties dictate signal processing in the ocular motor system. P/Q channel mutations can engender multiple effects at the single neuron, circuit, and behavioral levels; correlating physiological and behavioral abnormalities in multiple allelic strains will ultimately facilitate determining which alterations of physiology are responsible for specific behavioral aberrations. We used videooculography to quantify ocular motor behavior in tottering mutants aged 3 mo to 2 yr and compared their performance to data previously obtained in the allelic mutant rocker and C57BL/6 controls. Tottering mutants shared numerous abnormalities with rocker, including upward deviation of the eyes at rest, increased vestibuloocular reflex (VOR) phase lead at low stimulus frequencies, reduced VOR gain at high stimulus frequencies, reduced gain of the horizontal and vertical optokinetic reflex, reduced time constants of the neural integrator, and reduced plasticity of the VOR as assessed in a cross-axis training paradigm. Unlike rocker, young tottering mutants exhibited normal peak velocities of nystagmus fast phases, arguing against a role for neuromuscular transmission defects in the attenuation of compensatory eye movements. Tottering also differed by exhibiting directional asymmetries of the gains of optokinetic reflexes. The data suggest at least four pathophysiological mechanisms (two congenital and two acquired) are required to explain the ocular motor deficits in the two Cacna1a mutant strains.

Cerebral Palsy for the Pediatric Eye Care Team—Part II: Diagnosis and Treatment of Ocular Motor Deficits

IntroductionCerebral palsy is a term used to describe a spectrum of neurological deficits resulting from damage to the developing nervous system. This paper, the second in a series of three articles, will present frequency, diagnosis, and management of the ocular motor deficits associated with CP. Topics for discussion will include the prevalence and type of strabismus, the effect of CP on eye movement systems, the efficacy of vision therapy for eye movement deficits, and strabismus surgery.MethodsIn 2002, a retrospective chart review of all cases of cerebral palsy referred to the St. Louis Children's Hospital Eye Center was done. Detailed data on the sensory and motor deficits documented in these children was collected. Also recorded was the management strategy and response to treatment.ResultsOf the 131 cases reviewed (mean age 5.2 years at presentation), 84 (64%) had strabismus: 55% esotropia and 27% exotropia. Of those patients tested for eye movement disorders 67 (61%) had evidence of instability of fixation; 85% of the patients had a pursuit deficit; and 80% had some type of deficit in performing saccades. Vergence was affected in 45% of our patients. Of the patients who underwent strabismus surgery, 67% achieved success after a mean number of 2.1 surgeries. Surgical success was associated with mild or moderate CP (P < .0005), and a stable preoperative angle. Six percent of our patients underwent vision therapy for strabismus or eye movement anomalies under the direction of an outside optometrist.ConclusionInfantile strabismus is significantly more common in children with CP than in the general pediatric population. Disorders of eye movements are also very common. Based on our experience and review of the literature there is no convincing evidence that vision therapy significantly improves eye movements or visual functioning. Approximately 2 of every 3 cases of nonaccommodative strabismus associated with CP can be successfully managed with conventional strabismus surgery, though most children will require at least two surgeries to achieve alignment.

Ocular manifestations of multiple sclerosis

Multiple sclerosis is an autoimmune demyelinating disorder of the nervous system that is commonly manifested by visual system involvement and that may initially present with ophthalmologic symptoms. This paper reviews recent findings regarding the ocular manifestations in multiple sclerosis. Manifestations of multiple sclerosis in the eye include both the afferent and efferent visual pathways. Optic neuritis, the most common ocular manifestation of multiple sclerosis, may be the initial clinical disease manifestation. Recent long-term follow-up data show that most patients with demyelinating optic neuritis have an excellent prognosis for recovery of central visual acuity. Evidence is emerging, however, for significant and broad reduction in both contrast sensitivity and color perception in multiple sclerosis patients despite near-normal visual acuities. Ocular motor deficits in multiple sclerosis include internuclear ophthalmoplegia and nystagmus, resulting in diplopia, oscillopsia, blurred visual, loss of stereopsis, and reading fatigue. Multiple sclerosis also may be associated with ocular inflammatory diseases, in particular pars planitis and retinal periphlebitis. Ocular findings may be initial manifestations of multiple sclerosis and may predict additional demyelinating events. Recognizing these syndromes and signs will help clinicians to properly evaluate the patient, formulate an appropriate differential diagnosis, be able to discuss the prognosis with the patient, and help develop an effective therapeutic plan.

Long-Term Follow-up and Prognosis of Orbital Apex Syndrome Resulting From Nasopharyngeal Rhabdomyosarcoma

Nasopharyngeal rhabdomyosarcoma may present with a variety of ophthalmic symptoms. Direct extension of the tumor into the orbital apex can lead to ophthalmoplegia and loss of vision. The prognosis for recovery of vision and ocular motility in patients with an orbital apex syndrome due to nasopharyngeal rhabdomyosarcoma is examined. Retrospective case series. Six eyes from four patients with nasopharyngeal rhabdomyosarcoma who presented to the Children';s Hospital of Philadelphia with a clinical orbital apex syndrome were identified. Complete ophthalmic examination, including visual acuity and extraocular motility at the time of presentation, was reviewed. Tumor extension into the orbital apex was confirmed radiographically. Follow-up ophthalmic evaluations were reviewed for all patients with an average follow-up of 5.5 +/- 3.1 years (range 1 to 8 years). Six eyes of four patients had limited ocular ductions along with marked loss of vision at presentation. All patients were treated with chemotherapy and radiation, with reduction of tumor mass. Ocular motility recovered in all patients, occurring by an average of 2.2 +/- 1.8 months after initiation of therapy. Four of six eyes had little or no recovery of visual acuity detected at long-term follow-up. Patients with ocular motor deficits in orbital apex syndromes caused by extension of nasopharyngeal rhabdomyosarcoma have an excellent prognosis for recovery after treatment of the tumor. The long-term prognosis for visual recovery, however, is poor.

Relative Atrophy of the Flocculus and Ocular Motor Dysfunction in SCA2 and SCA6

Two hereditary ataxia syndromes show distinct profiles of region-specific atrophy and ocular motor deficits. Selective pontine atrophy is associated with slowed saccades in ataxin-2 mutations, and selective floccular atrophy is associated with impaired pursuit and gaze-holding abnormalities in Ca(V)2.1 mutations. Although the flocculus seems to be spared relative to the pons in ataxin-2 mutations, and pursuit and gaze-holding appear to be relatively normal, these can be difficult to assess at the bedside, as corrective saccades are also slow and hard to discern. Here, we show the presence of significant floccular atrophy compared with controls in both ataxin-2 and Ca(V)2.1 mutations, which raises the possibility that abnormalities of smooth pursuit or gaze-holding are present in both conditions.

Cerebral Palsy for the Pediatric Eye Care Team—Part 1: Epidemiology, Pathogenesis, and Systemic Findings

Cerebral palsy (CP) is a term used to describe a spectrum of neurological deficits resulting from damage to the immature brain. It is a chronic, nonprogressive motor disorder that affects posture, muscle tone, and movement, and therefore commonly results in ophthalmologic abnormalities such as strabismus and eye movement disorders. A basic understanding of CP and its effects will assist the clinician in the diagnosis, prognosis, and management of associated ophthalmologic disorders. This first, in a series of three articles, reviews the definition, epidemiology, pathogenesis, and classification of CP, as well as current management of the postural and motor effects. Results include a retrospective review of 131 consecutive cases of cerebral palsy referred to the Department of Ophthalmology by the Cerebral Palsy Center at the St. Louis Children's Hospital. The second article in the series will present the frequency, diagnosis, and management of the ocular motor deficits associated with CP. Article three will discuss the evaluation of visual acuity, management of decreased vision, and the frequency and type of binocular vision deficits associated with CP.

Acute migrainous vertigo: clinical and oculographic findings

Migrainous vertigo (MV) is an increasingly recognized cause of episodic vertigo. However, the pathophysiology of MV is still a matter of speculation and it is not known to what extent the dysfunction is located in the central or peripheral vestibular system. The aim of this prospective study was to describe the clinical spectrum of acute MV and to clarify which structures of the vestibular system are involved. Testing of 20 patients with acute MV included neuro-otological examination, recording of spontaneous and positional nystagmus with 3D video-oculography, and audiometry. Pathological nystagmus was observed in 70% of patients during acute MV: six had isolated spontaneous nystagmus, five had isolated positional nystagmus and three had a combination of the two. Only a few patients showed additional ocular motor deficits. Imbalance was observed in all patients except one. Hearing was not affected in any patient during the attack. The findings during acute MV point to central-vestibular dysfunction in 10 patients (50%) and to peripheral vestibular dysfunction in three patients (15%). In the remaining seven patients (35%) the site of involvement could not be determined with certainty. MV should be considered in the differential diagnosis of vertigo with spontaneous and positional nystagmus and can present both as a central and a peripheral vestibular disorder.

Paucity of horizontal connections for binocular vision in V1 of naturally strabismic macaques: Cytochrome oxidase compartment specificity

To describe the structural basis for lack of binocular fusion in strabismic primates, we investigated intrinsic horizontal connections within striate cortex (area V1) of normal and strabismic, adult macaque monkeys. The strabismic animals had early-onset natural esotropia (the visual axes deviated nasally), normal visual acuity in each eye, and the constellation of ocular motor deficits that typify human infantile strabismus. Horizontal patchy connections and synaptic boutons were labeled by injections of the neuronal tracer biotinylated dextran amine. Ocular dominance columns (ODCs), and blob vs. interblob compartments, were revealed by using cytochrome oxidase (CO). In layers 2/3 and 4B of the strabismic monkeys, patchy projections and boutons terminated much more frequently in same-eye (73%) as opposed to opposite-eye (27%) ODCs (normal monkeys 58% and 42%, respectively). The deficiency of binocular connections in the strabismic cortex was evident qualitatively as a "skip" pattern, in which every other row of ODCs had labeled patches. Analysis of V1 in normal monkeys revealed that the deficits in strabismic V1 were due mainly to a loss of binocular connections between neurons in CO-interblob compartments. In both normal and strabismic monkeys: (1) CO-blob compartment neurons showed a more pronounced bias for monocular connectivity, and (2) commitment of connections to the same CO-compartment as the injection site (blob-to-blob, or interblob-to-interblob) was moderately strong (64%) but far from absolute. These findings help elucidate the relative roles of visual experience vs. innate mechanisms in the development of axonal connections between ocular dominance domains and compartments within macaque V1. They also provide the first detailed description of the V1 maldevelopments associated with unrepaired natural, infantile-onset strabismus in primates.

Chiasmal syndromes.

This review of the more recent literature and testing strategies in patients with chiasmal syndromes focuses on the clinical evaluation and management of these patients. Visual loss is often the initial manifestation of disorders involving the optic chiasm. Hemianopic defects and preferential involvement of the temporal visual field are the earliest and most common visual deficits. Progression of the lesion may cause compression of adjacent structures, including the optic nerves and cavernous sinuses, and may result in more profound visual loss, ocular motor deficits, and hypopituitarism. Although a number of modalities have been used to assess visual function in patients with chiasmal disorders, perimetry remains the most effective means of detecting and following the visual deficit. Most chiasmal syndromes can be categorized as intrinsic (thickening of the chiasm itself) or extrinsic (compression of the chiasm from an adjacent structure). Magnetic resonance imaging is the best mode of neuroimaging for most chiasmal lesions and may also provide clues to the etiology of an isolated chiasmal syndrome.

Ptosis in patients with hemispheric strokes. Averbuch-Heller L. Leigh RJ. Mermelstein V. Zagalsky L. Streifler JY. Neurology 2002;58:620–624

Ptosis caused by lesions of the cerebral hemispheres without involvement of the third cranial nerves or oculosympathetic pathways is considered rare. So-called cerebral ptosis has been most often reported with unilateral, usually right hemispheric lesions. However, the frequency of cerebral ptosis in patients with strokes has not received systematic study. The purpose of this study was to determine the frequency of ptosis in patients with acute hemispheric stroke and to identify stroke features associated with ptosis. Eyelid function was studied in 64 consecutive patients with acute hemispheric stroke and 40 age-matched subjects with no known neurologic disease. All underwent comprehensive neuroophthalmologic and general neurologic examination within 48 hours of admission, including measurement of palpebral fissures, marginal reflex distance, and range of upper lid movement. Only patients who could cooperate with eyelid testing were included Brain CT scans were obtained for all patients. Neurogenic ptosis was found in 24 patients (37.5%) with stroke, which was bilateral in 10 patients and unilateral in 14. None of the control subjects had neurogenic ptosis. All patients with stroke with ptosis had a hemiparesis, most often contralateral to the side of the ptosis in those patients with unilateral or highly asymmetric ptosis. CT evidence of right-sided hemispheric cortical infarction was more common in patients with strokes with ptosis. Rightward gaze deviation and upgaze paresis were more common (P < .05) in the patients with ptosis compared with others who had had strokes. In five patients with large hemispheric infarction, complete bilateral or asymmetric ptosis was the first sign of imminent herniation, preceding pupillary dilatation and ocular motor deficits. The authors conclude that ptosis occurs frequently in patients with hemispheric strokes, especially in association with right hemispheric lesions. Complete bilateral ptosis is usually caused by large infarctions and may be a premonitory sign of an impending herniation.—Nancy J. Newman

Ocular Abnormalities in Neurofibromatosis 2

Purpose To evaluate the ocular abnormalities in patients with clinically diagnosed neurofibromatosis 2 and asymptomatic gene carriers. Methods Probands were ascertained through a surgical otolaryngology practice. In a cross-sectional study, we examined 49 patients with neurofibromatosis 2, 30 offspring of patients, and, as a comparison group, 18 parents and siblings of patients with sporadic neurofibromatosis 2. The examination included a complete neuro-ophthalmic assessment, physical examination, and, for patients and first-degree relatives at risk, cranial and spinal magnetic resonance imaging with gadolinium enhancement, if not previously performed. Results The most common ocular abnormalities were posterior subcapsular or capsular, cortical, or mixed lens opacities in 33 (67%) of 49 patients with neurofibromatosis 2 and retinal hamartomas in 11 (22%). We used segregation analysis to determine the mutation carrier status of six at-risk offspring who were 30 years old or younger in two multigeneration families. Three asymptomatic mutation carriers had cataracts, whereas those who were predicted not to carry the mutation did not have cataracts. Asymptomatic mutation carriers may have developmental abnormalities of the eye that are detectable in childhood or adolescence, a finding that may assist in early diagnosis of the disease. Conclusions A variety of ocular abnormalities are present in neurofibromatosis 2, including cataracts, retinal hamartomas, and ocular motor deficits. Many of these are developmental or acquired early in life and may assist in presymptomatic diagnosis. For screening at-risk relatives of patients with neurofibromatosis 2, the types of cataract that are most suggestive of neurofibromatosis 2 are plaque-like posterior subcapsular or capsular cataract and cortical cataract with onset under the age of 30 years.