Idiopathic intracranial hypertension (IIH, pseudotumor cerebri) is a syndrome of elevated intracranial pressure of unknown cause that occurs predominantly in obese women of childbearing age. It is a diagnosis of exclusion and, therefore, other causes of increased intracranial pressure must be sought with history, imaging, and cerebrospinal fluid examination before the diagnosis can be made. IIH produces symptoms and signs of increased intracranial pressure, including papilledema. If untreated, papilledema can cause progressive irreversible visual loss and optic atrophy. The treatment approach depends on the severity and time course of symptoms and visual loss, as determined by formal visual field testing. The main goals of treatment are alleviation of symptoms, including headache, and preservation of vision. All overweight IIH patients should be encouraged to enter a weight-management program with a goal of 5% to 10% weight loss, along with a low-salt diet. When there is mild visual loss, medical treatment with acetazolamide should be initiated. Other medical treatments can be added or substituted when acetazolamide is insufficient as monotherapy or poorly tolerated. When visual loss is more severe or rapidly progressive, surgical interventions, such as optic nerve sheath fenestration or cerebrospinal fluid shunting, may be required to prevent further irreversible visual loss. The choice of intervention depends on the relative severity of symptoms and visual loss, as well as local expertise. At present, the role of transverse venous sinus stenting remains unclear. Although there are no evidence-based data to guide therapy, there is an ongoing randomized double-blind placebo-controlled treatment trial, investigating diet and acetazolamide therapy for IIH.
Idiopathic intracranial hypertension; Treatment; Recognition; Management; Pseudotumor cerebri; Papilledema; Vision loss; Acetazolamide; Topiramate; Optic nerve sheath fenestration; Cerebrospinal fluid shunting
Miller Fisher syndrome (MFS) is a rare immune-mediated neuropathy that commonly presents with diplopia following the acute onset of complete bilateral external ophthalmoplegia. Ophthalmoplegia is often accompanied by other neurological deficits such as ataxia and areflexia that characterize MFS. Although MFS is a clinical diagnosis, serological confirmation is possible by identifying the anti-GQ1b antibody found in a majority of affected patients. We report a patient with MFS who presented with clinical signs suggestive of ocular myasthenia gravis, but in whom the correct diagnosis was made on the basis of serological testing for the anti-GQ1b antibody.
An 81-year-old white man presented with an acute onset of diplopia following a mild gastrointestinal illness. Clinical examination revealed complete bilateral external ophthalmoplegia and left-sided ptosis. He developed more marked bilateral ptosis, left greater than right, with prolonged attempted upgaze. He was also noted to have a Cogan’s lid twitch. Same day evaluation by a neuro-ophthalmologist revealed mild left-sided facial and bilateral orbicularis oculi weakness. He had no limb ataxia, but exhibited a slightly wide-based gait with difficulty walking heel-to-toe. A provisional diagnosis of ocular myasthenia gravis was made and anticholinesterase inhibitor therapy was initiated. However, his symptoms did not improve and serological testing was positive for the anti-GQ1b IgG antibody, supporting a diagnosis of MFS.
Although the predominant ophthalmic feature of MFS is complete bilateral external ophthalmoplegia, it should be recognized that MFS has variable associations with lid and pupillary dysfunction. Such confounding neuro-ophthalmic features require a thorough history, neurological examination, neuroimaging, and serological testing for the anti-GQ1b antibody to arrive at a diagnosis of MFS.
Miller Fisher syndrome; anti-ganglioside antibody; ophthalmoplegia; diplopia; cranial neuropathies; multiple; myasthenia gravis; ocular
Idiopathic intracranial hypertension (IIH) is a condition of unknown etiology often encountered in neurologic practice. It produces non-localizing symptoms and signs of raised intracranial pressure and, when left untreated, can result in severe irreversible visual loss. It most commonly occurs in obese women of childbearing age, but it can also occur in children, men, non-obese adults, and older adults. While it is frequently associated with obesity, it can be associated with other conditions, such as obstructive sleep apnea and transverse cerebral venous sinus stenoses. Recent identification of subgroups at high risk for irreversible visual loss, including black patients, men, and patients with fulminant forms of IIH, help guide the optimal management and follow-up. Ongoing studies of venous anatomy and physiology in IIH patients, as well as a recently begun randomized clinical treatment trial, should provide more insights into this common yet poorly understood syndrome of isolated intracranial hypertension.
Idiopathic Intracranial Hypertension; Venous Sinus Stenosis; Ventriculoperitoneal Shunting; Lumboperitoneal Shunting; Optic Nerve Sheath Fenestration; Venous Sinus Stenting
For Listing’s law to be obeyed during eye movements, the “half-angle rule” must be satisfied: the eye velocity axis must tilt away from Listing’s plane by half the angle of eye position eccentricity from primary position. We aimed to determine if this rule is satisfied during horizontal and vertical pursuit compared with saccades. Three-dimensional (3-d) eye rotation data were acquired from five normal head-fixed humans using the search coil technique. Saccades were recorded in response to 40° horizontal or vertical steps in target position, at different elevations and azimuths. Pursuit was recorded while tracking a target moving horizontally or vertically at 20°/s, with peak-to-peak amplitude of 40°, at the same elevations and azimuths. First- and second-order surfaces were fitted to 3-d eye position data from periods of fixation. In all subjects, eye positions did not lie on a planar surface, but on a twisted surface in 3-d space. The tilt-angle coefficient (TAC) during saccades and pursuit was calculated as the ratio of the angle of eye velocity axis tilt to the angle of eye position eccentricity. During horizontal saccades and pursuit, mean TACs were 0.58 and 0.64, respectively. During vertical saccades and pursuit, mean TACs were 0.35 and 0.43, respectively, and lower than their horizontal counterparts (p<0.05). These findings suggest that Listing’s law is not perfectly satisfied during saccades or pursuit. On the basis of model simulations, we propose that the discrepancy in horizontal and vertical TACs causes eye positions to lie on a twisted rather than a planar surface.
Saccades; Smooth Pursuit; Kinematics; Listing’s Law; Donders’ Law
Several studies have suggested racial differences in the prevalence of optic nerve head drusen (ONHD). We aimed to determine the percentage of patients with ONHD who are black, and to describe the clinical, ophthalmoscopic, and perimetry findings in these patients.
We conducted a retrospective chart review of all patients with ONHD seen at our institution between 1989 and 2010. Only black patients with ONHD confirmed on either funduscopy or B-scan ultrasonography were included. Demographic and clinical findings in these patients were recorded and analyzed.
Of 196 patients with confirmed ONHD, 10 (5.1%) were black (7 women; ages 8–61 years). Six of the 10 patients had bilateral ONHD. The ONHD were buried in 11 of 16 eyes with ONHD, and exposed in 5 of 16 eyes. Fifteen of 16 eyes with ONHD had small cupless optic nerve heads. Visual fields were normal in 4 of 16 eyes with ONHD. In the other eyes, visual field defects included an enlarged blind spot (5 eyes), constricted field (5 eyes), nasal defect (2 eyes), central defect (1 eye), and generalized depression (1 eye). Visual field defects were present in 4 of 5 eyes (80%) with exposed ONHD and 8 of 11 eyes (72.7%) with buried ONHD. None of the patients were related and none of their examined family members had exposed ONHD on funduscopic examination.
ONHD are rare in blacks, possibly due to the presence of a larger cup-to-disc ratio or a lack of predisposing genetic factors. Visual field defects are common in black patients with both exposed and buried ONHD.
Optic Nerve; Drusen; Ethnicity
When normal subjects fix their eyes upon a stationary target, their gaze is not perfectly still, due to small movements that prevent visual fading. Visual loss is known to cause greater instability of gaze, but reported comparisons with normal subjects using reliable measurement techniques are few. We measured binocular gaze using the magnetic search coil technique during attempted fixation (monocular or binocular viewing) of 4 individuals with childhood-onset of monocular visual loss, 2 individuals with late-onset monocular visual loss due to age-related macular degeneration, 2 individuals with bilateral visual loss, and 20 healthy control subjects. We also measured saccades to visual or somatosensory cues. We tested the hypothesis that gaze instability following visual impairment is caused by loss of inputs that normally optimize the performance of the neural network (integrator), which ensures both monocular and conjugate gaze stability. During binocular viewing, patients with early-onset monocular loss of vision showed greater instability of vertical gaze in the eye with visual loss and, to a lesser extent, in the normal eye, compared with control subjects. These vertical eye drifts were much more disjunctive than upward saccades. In individuals with late monocular visual loss, gaze stability was more similar to control subjects. Bilateral visual loss caused eye drifts that were larger than following monocular visual loss or in control subjects. Accurate saccades could be made to somatosensory cues by an individual with acquired blindness, but voluntary saccades were absent in an individual with congenital blindness. We conclude that the neural gaze-stabilizing network, which contains neurons with both binocular and monocular discharge preferences, is under adaptive visual control. Whereas monocular visual loss causes disjunctive gaze instability, binocular blindness causes both disjunctive and conjugate gaze instability (drifts and nystagmus). Inputs that bypass this neural network, such as projections to motoneurons for upward saccades, remain conjugate.
Acquired pendular nystagmus (APN) occurs with multiple sclerosis (MS) and oculopalatal tremor (OPT); distinct features of the nystagmus have led to the development of separate models for the pathogenesis. APN in MS has been attributed to instability in the neural integrator, which normally ensures steady gaze. APN in OPT may result from electrotonic coupling between neurons in the hypertrophied inferior olivary nucleus, which induces maladaptive learning in cerebellar cortex. We tested these two hypotheses by analyzing the effects of gabapentin, memantine, and baclofen on both forms of nystagmus. No drug changed the dominant frequency of either form of APN, but the variability of frequency was affected with gabapentin and memantine in patients with OPT. The amplitude of APN in both MS and OPT was reduced with gabapentin and memantine, but not baclofen. Analyzing the effects of drug therapies on ocular oscillations provides a novel approach to test models of nystagmus.
cerebellum; inferior olive; plasticity; learning; Guillain–Mollaret triangle; multiple sclerosis
We studied the dynamics and kinematics of saccades in a patient with severe ocular myasthenia before and after treatment with intravenous immunoglobulin (IVIG). Before therapy, horizontal saccades were hypometric, but faster than similar-sized saccades made by normal subjects. During a 5-minute test period, saccades decreased in size (fatigue effect), but remained faster than those of controls. Listing’s plane of the eye with greater ophthalmoplegia was increased in thickness. After IVIG treatment, the range of eye movements improved, but saccades remained faster than those of controls. Also, no fatigue was observed and the thickness of Listing’s plane was reduced towards the normal range. Increased peak velocity, despite progressive hypometria due to fatigue, supports the hypothesis that the pale global extraocular muscle fibers are relatively spared in myasthenia. Involvement of other extraocular muscle fiber types leads to limited range of eye movements and an increase in the thickness of Listing’s plane.
saccades; fatigue; pale extraocular muscle fibers; Listing’s plane
Hemi-seesaw nystagmus (hemi-SSN) is a jerk-waveform nystagmus with conjugate torsional and disjunctive vertical components. Halmagyi et al. in Brain 117(Pt 4):789–803 (1994), reported hemi-SSN in patients with unilateral lesions in the vicinity of the Interstitial Nucleus of Cajal (INC) and suggested that an imbalance in projections from the vestibular nuclei to the INC was the source of the nystagmus. However, this hypothesis was called into question by Helmchen et al. in Exp Brain Res 119(4):436–452 (1998), who inactivated INC in monkeys with muscimol (a GABAA agonist) and induced failure of vertical gaze-holding (neural integrator) function but not hemi-SSN. We injected 0.1–0.2 μl of 2% muscimol into the supraoculomotor area, 1–2 mm dorso-lateral to the right oculomotor nucleus and caudal to the right INC. A total of seven injections in two juvenile rhesus monkeys were performed. Hemi-SSN was noted within 5–10 min after injection for six of the injections. Around the time the hemi-SSN began, a small skew deviation also developed. However, there was no limitation of horizontal or vertical eye movements, suggesting that the nearby oculomotor nucleus was not initially compromised. Limitations in eye movement range developed about ½–1 h following the injections. Clinical signs that were observed after the animal was released to his cage included a moderate to marked head tilt toward the left (contralesional) side, consistent with an ocular tilt reaction. We conclude that hemi-SSN can be caused by lesions just caudal to the INC, whereas lesions of the INC itself cause down-beat nystagmus and vertical gaze-holding failure, as demonstrated by Helmchen et al. Combined deficits may be encountered with lesions that involve several midbrain structures.
Hemi-seesaw nystagmus; Rhesus; Muscimol; Oculomotor
We review current pharmacological treatments for peripheral and central vestibular disorders, and ocular motor disorders that impair vision, especially pathological nystagmus. The prerequisites for successful pharmacotherapy of vertigo, dizziness, and abnormal eye movements are the “4 D’s”: correct diagnosis, correct drug, appropriate dosage, and sufficient duration. There are seven groups of drugs (the “7 A’s”) that can be used: antiemetics; anti-inflammatory, anti-Ménière’s, and anti-migrainous medications; anti-depressants, anti-convulsants, and aminopyridines. A recovery from acute vestibular neuritis can be promoted by treatment with oral corticosteroids. Betahistine may reduce the frequency of attacks of Ménière’s disease. The aminopyridines constitute a novel treatment approach for downbeat and upbeat nystagmus, as well as episodic ataxia type 2 (EA 2); these drugs may restore normal “pacemaker” activity to the Purkinje cells that govern vestibular and cerebellar nuclei. A limited number of trials indicate that baclofen improves periodic alternating nystagmus, and that gabapentin and memantine improve acquired pendular and infantile (congenital) nystagmus. Preliminary reports suggest suppression of square-wave saccadic intrusions by memantine, and ocular flutter by beta-blockers. Thus, although progress has been made in the treatment of vestibular neuritis, some forms of pathological nystagmus, and EA 2, controlled, masked trials are still needed to evaluate treatments for many vestibular and ocular motor disorders, including betahistine for Ménière’s disease, oxcarbazepine for vestibular paroxysmia, or metoprolol for vestibular migraine.
Vertigo; Dizziness; Vestibular neuritis; Ménière’s disease; Vestibular paroxysmia; Vestibular migraine; Episodic ataxia type 2; Downbeat nystagmus; Upbeat nystagmus; Pendular nystagmus; Periodic alternating nystagmus; Infantile nystagmus; Square-wave saccadic intrusion; Ocular flutter; Opsoclonus
We conducted a masked, cross-over, therapeutic trial of gabapentin (1200mg/day) versus memantine (40mg/day) for acquired nystagmus in 10 patients (28–61 years; 7 female; MS: 3, post-stroke: 6, post-traumatic: 1). Nystagmus was pendular in 6 patients (oculopalatal tremor: 4, MS: 2) and jerk upbeat, hemi-seesaw, torsional, or upbeat-diagonal in each of the others. Both drugs reduced median eye speed (p<0.001), gabapentin by 32.8% and memantine by 27.8%, and improved visual acuity (p<0.05). Each patient improved with one or both drugs. Side-effects included unsteadiness with gabapentin and lethargy with memantine. Both drugs should be considered as treatment for acquired forms of nystagmus.
nystagmus; oscillopsia; multiple sclerosis; oculopalatal tremor
We report two patients with genetically-confirmed spinocerebellar ataxia type 7 (SCA-7), who presented with progressive central visual loss and dyschromatopsia. Ocular funduscopic changes were subtle, with only mild retinal artery attenuation and subtle macular changes. Despite this, the electroretinogram (ERG) was abnormal in both patients. Both patients also had slowing of saccades and partially limited ductions, although neither reported diplopia. Although the older patient had cerebellar ataxia, the younger only had an unsteady tandem gait. This constellation of signs should indicate SCA-7 as a diagnostic possibility, and prompt further investigation with ERG and genetic studies.
Spinocerebellar Ataxia Type-7; Retinopathy; Ophthalmoplegia; Electroretinography
The central projections of the anterior semicircular canals are thought to be conveyed from the vestibular nuclei to the ocular motor nuclei in the midbrain by three distinct brainstem pathways: the medial longitudinal fasciculus, crossing ventral tegmental tract, and brachium conjunctivum. There is controversy as to whether upbeat nystagmus could result from lesions involving each of these pathways. We report a 52-year-old man who presented with a contralesional fourth nerve palsy and primary position upbeat-torsional nystagmus due to a small unilateral dorsal ponto-mesencephalic lymphomatous deposit. We postulate that the upbeat-torsional nystagmus was caused by involvement of the brachium conjunctivum, which lies adjacent to the fourth nerve fascicles at the dorsal ponto-mesencephalic junction, but we cannot exclude involvement of the crossing ventral tegmental tract. Our observations suggest that, in humans, excitatory upward-torsional eye movement signals from the anterior semicircular canals could be partly conveyed to the midbrain by the brachium conjunctivum.
Upbeat Nystagmus; Torsional Nystagmus; Fourth Nerve Palsy; Pons; Mesencephalon; Brachium Conjunctivum