Transverse sinus stenting for idiopathic intracranial hypertension: a review of 52 patients and of model predictions.

BACKGROUND AND PURPOSE: Transverse sinus stenosis is common in patients with IIH. While the role of transverse sinus stenosis in IIH pathogenesis remains controversial, modeling studies suggest that stent placement within a transverse sinus stenosis with a significant pressure gradient should decrease cerebral venous pressure, improve CSF resorption in the venous system, and thereby reduce intracranial (CSF) pressure, improving the symptoms of IIH and reducing papilledema. We aimed to determine if IIH could be reliably treated by stent placement in transverse sinus stenosis. MATERIALS AND METHODS: We reviewed the clinical, venographic, and intracranial pressure data before and after stent placement in transverse sinus stenosis in 52 of our own patients with IIH unresponsive to maximum acceptable medical treatment, treated since 2001 and followed between 2 months and 9 years. RESULTS: Before stent placement, the mean superior sagittal sinus pressure was 34 mm Hg (462 mm H(2)0) with a mean transverse sinus stenosis gradient of 20 mm Hg. The mean lumbar CSF pressure before stent placement was 322 mm H(2)O. In all 52 patients, stent placement immediately eliminated the TSS pressure gradient, rapidly improved IIH symptoms, and abolished papilledema. In 6 patients, symptom relapse (headache) was associated with increased venous pressure and recurrent stenosis adjacent to the previous stent. In these cases, placement of another stent again removed the transverse sinus stenosis pressure gradient and improved symptoms. Of the 52 patients, 49 have been cured of all IIH symptoms. CONCLUSIONS: These findings indicate a role for transverse sinus stent placement in the management of selected patients with IIH.

Effects of acetazolamide on infantile nystagmus syndrome waveforms: comparisons to contact lenses and convergence in a well-studied subject.

AIM: To determine if acetazolamide, an effective treatment for certain inherited channelopathies, has therapeutic effects on infantile nystagmus syndrome (INS) in a well-studied subject, compare them to other therapies in the same subject and to tenotomy and reattachment (T&R) in other subjects. METHODS: Eye-movement data were taken using a high-speed digital video recording system. Nystagmus waveforms were analyzed by applying an eXpanded Nystagmus Acuity Function (NAFX) at different gaze angles and determining the Longest Foveation Domain (LFD). RESULTS: Acetazolamide improved foveation by both a 59.7% increase in the peak value of the NAFX function (from 0.395 to 0.580) and a 70% broadening of the NAFX vs Gaze Angle curve (the LFD increased from 20° to 34°). The resulting U-shaped improvement in the percent NAFX vs Gaze Angle curve, varied from ~60% near the NAFX peak to over 1000% laterally. The therapeutic improvements in NAFX from acetazolamide (similar to T&R) were intermediate between those of soft contact lenses and convergence, the latter was best; for LFD improvements, acetazolamide and contact lenses were equivalent and less effective than convergence. Computer simulations suggested that damping the central oscillation driving INS was insufficient to produce the foveation improvements and increased NAFX values. CONCLUSION: Acetazolamide resulted in improved-foveation INS waveforms over a broadened range of gaze angles, probably acting at more than one site. This raises the question of whether hereditary INS involves an inherited channelopathy, and whether other agents with known effects on ion channels should be investigated as therapy for this condition.

Evaluation of optic neuropathy in multiple sclerosis using low-contrast visual evoked potentials.

BACKGROUND: Contrast acuity (identification of low-contrast letters on a white background) is frequently reduced in patients with demyelinating optic neuropathy associated with multiple sclerosis (MS), even when high-contrast (Snellen) visual acuity is normal. Since visual evoked potentials (VEPs) induced with high-contrast pattern-reversal stimuli are typically increased in latency in demyelinating optic neuropathy, we asked if VEPs induced with low-contrast stimuli would be more prolonged and thus helpful in identifying demyelinating optic neuropathy in MS. METHODS: We studied 15 patients with clinically definite MS and 15 age-matched normal controls. All subjects underwent a neuro-ophthalmologic assessment, including measurement of high-contrast visual acuity and low-contrast acuities with 25%, 10%, 5%, 2.5%, and 1.25% contrast Sloan charts. In patients with MS, peripapillary retinal nerve fiber layer (RNFL) thickness was determined using optical coherence tomography. Monocular VEPs were induced using pattern-reversal checkerboard stimuli with 100% and 10% contrast between checks, at 5 spatial frequencies (8-130 minutes of arc). RESULTS: VEP latencies were significantly increased in response to low- compared with high-contrast stimuli in both groups. VEP latencies were significantly greater in patients with MS than controls for both high- and low-contrast stimuli. VEP latencies correlated with high- and low-contrast visual acuities and RNFL thickness. VEPs were less likely to be induced with low- than with high-contrast stimuli in eyes with severe residual visual loss. CONCLUSIONS: Visual evoked potentials obtained in patients with multiple sclerosis using low-contrast stimuli are increased in latency or absent when compared with those obtained using high-contrast stimuli and, thus, may prove to be helpful in identifying demyelinating optic neuropathy.

Evidence for three-dimensional cortical control of gaze from epileptic patients.

Electrophysiological studies in primates indicate that the eye fields of the cerebral hemispheres control gaze in three-dimensional space, and contain neurons that encode both conjugate (versive) and vergence eye movements. Two patients with epilepsy who exhibited disconjugate contraversive horizontal eye movements are described, one during electrical stimulation of the frontal eye fields and the other during focal seizures. We postulate that these eye movements resulted from combined contralateral version and vergence, and suggest that human cortical eye fields also govern visual search in a three-dimensional world, shifting the point of fixation between targets lying in different directions and at different depths.

Nonarteritic anterior ischemic optic neuropathy with PDE-5 inhibitors for erectile dysfunction.

Phosphodiesterase type-5 (PDE-5) inhibitors are well tolerated and efficacious treatments for male erectile dysfunction that currently rank among the best-selling drugs worldwide. Since their introduction 10 years ago, there have been a number of reports of patients developing, within hours of PDE-5 inhibitor use, permanent visual loss due to nonarteritic anterior ischemic optic neuropathy (NAION), a common optic neuropathy that results from ischemia of the optic nerve head. In some of the cases, visual loss recurred upon rechallenge with the drug. However, as the bulk of the evidence suggesting a relationship between PDE-5 inhibitor use and NAION comes from case reports and small series, it is difficult to ascertain if a cause-effect relationship truly exists. In this paper, following a review of the transient visual side effects of PDE-5 inhibitors and NAION, we discuss the evidence for and against NAION occurring as a complication of PDE-5 inhibitor use.

Tuberculous cranial pachymeningitis.

We describe two immunocompetent patients with tuberculous cranial pachymeningitis. Both patients underwent biopsy after focal dural thickening was identified on MRI. Histopathologic examination of tissue revealed necrotizing granulomatous inflammation. PCR for Mycobacterium tuberculosis DNA was negative on CSF but positive on tissue. Both patients responded to antituberculous therapy. Although uncommon as a cause of cranial pachymeningitis, tuberculosis should be considered, since it responds well to treatment.

The human horizontal vestibulo-ocular reflex in response to active and passive head impulses after unilateral vestibular deafferentation.

We studied the compensatory eye movements made by subjects with unilateral vestibular deficits in response to passive (unpredictable, manually generated) and active (predictable, self-generated) head impulses. A typical head impulse is a brief, low-amplitude (15-20 degrees ), high-velocity (150-350 degrees /s), high-acceleration (4000-6000 degrees /s(2)), yaw head-on-trunk rotation. In the initial 75 ms of the response, the vestibulo-ocular reflex gain was significantly higher during active head impulses to both ipsilesional and contralesional sides, than during passive impulses. Mean gains were 0.15 (ipsilesional passive), 0.44 (ipsilesional active), 0.5 (contralesional passive), and 0.76 (contralesional active). Differences between active and passive head impulses were present from near the onset of head rotation. The mechanism for producing this behavior is unclear, but the findings could be related to enhanced sensitivity of second-order neurons during active head impulses. However, even with active movements, there is still a large and statistically significant asymmetry in the eye-movement responses for ipsilesional as opposed to contralesional head rotations. After 75 ms, rapid corrective eye movements often were generated to reduce any remaining gaze error.

Role of muscle pulleys in producing eye position-dependence in the angular vestibuloocular reflex: a model-based study.

It is well established that the head and eye velocity axes do not always align during compensatory vestibular slow phases. It has been shown that the eye velocity axis systematically tilts away from the head velocity axis in a manner that is dependent on eye-in-head position. The mechanisms responsible for producing these axis tilts are unclear. In this model-based study, we aimed to determine whether muscle pulleys could be involved in bringing about these phenomena. The model presented incorporates semicircular canals, central vestibular pathways, and an ocular motor plant with pulleys. The pulleys were modeled so that they brought about a rotation of the torque axes of the extraocular muscles that was a fraction of the angle of eye deviation from primary position. The degree to which the pulleys rotated the torque axes was altered by means of a pulley coefficient. Model input was head velocity and initial eye position data from passive and active yaw head impulses with fixation at 0 degrees, 20 degrees up and 20 degrees down, obtained from a previous experiment. The optimal pulley coefficient required to fit the data was determined by calculating the mean square error between data and model predictions of torsional eye velocity. For active head impulses, the optimal pulley coefficient varied considerably between subjects. The median optimal pulley coefficient was found to be 0.5, the pulley coefficient required for producing saccades that perfectly obey Listing's law when using a two-dimensional saccadic pulse signal. The model predicted the direction of the axis tilts observed in response to passive head impulses from 50 ms after onset. During passive head impulses, the median optimal pulley coefficient was found to be 0.21, when roll gain was fixed at 0.7. The model did not accurately predict the alignment of the eye and head velocity axes that was observed early in the response to passive head impulses. We found that this alignment could be well predicted if the roll gain of the angular vestibuloocular reflex was modified during the initial period of the response, while pulley coefficient was maintained at 0.5. Hence a roll gain modification allows stabilization of the retinal image without requiring a change in the pulley effect. Our results therefore indicate that the eye position-dependent velocity axis tilts could arise due to the effects of the pulleys and that a roll gain modification in the central vestibular structures may be responsible for countering the pulley effect.

Vertical eye position-dependence of the human vestibuloocular reflex during passive and active yaw head rotations.

Vertical eye position-dependence of the human vestibuloocular reflex during passive and active yaw head rotations. The effect of vertical eye-in-head position on the compensatory eye rotation response to passive and active high acceleration yaw head rotations was examined in eight normal human subjects. The stimuli consisted of brief, low amplitude (15-25 degrees ), high acceleration (4,000-6,000 degrees /s2) yaw head rotations with respect to the trunk (peak velocity was 150-350 degrees /s). Eye and head rotations were recorded in three-dimensional space using the magnetic search coil technique. The input-output kinematics of the three-dimensional vestibuloocular reflex (VOR) were assessed by finding the difference between the inverted eye velocity vector and the head velocity vector (both referenced to a head-fixed coordinate system) as a time series. During passive head impulses, the head and eye velocity axes aligned well with each other for the first 47 ms after the onset of the stimulus, regardless of vertical eye-in-head position. After the initial 47-ms period, the degree of alignment of the eye and head velocity axes was modulated by vertical eye-in-head position. When fixation was on a target 20 degrees up, the eye and head velocity axes remained well aligned with each other. However, when fixation was on targets at 0 and 20 degrees down, the eye velocity axis tilted forward relative to the head velocity axis. During active head impulses, the axis tilt became apparent within 5 ms of the onset of the stimulus. When fixation was on a target at 0 degrees, the velocity axes remained well aligned with each other. When fixation was on a target 20 degrees up, the eye velocity axis tilted backward, when fixation was on a target 20 degrees down, the eye velocity axis tilted forward. The findings show that the VOR compensates very well for head motion in the early part of the response to unpredictable high acceleration stimuli-the eye position- dependence of the VOR does not become apparent until 47 ms after the onset of the stimulus. In contrast, the response to active high acceleration stimuli shows eye position-dependence from within 5 ms of the onset of the stimulus. A model using a VOR-Listing's law compromise strategy did not accurately predict the patterns observed in the data, raising questions about how the eye position-dependence of the VOR is generated. We suggest, in view of recent findings, that the phenomenon could arise due to the effects of fibromuscular pulleys on the functional pulling directions of the rectus muscles.

Unilateral vestibular deafferentation produces no long-term effects on human active eye-head coordination.

We tested the hypothesis that the reason some patients compensate well after unilateral vestibular deafferentation (uVD) and others do not could be due to differences in eye-head coordination or in blink characteristics during natural, active head movements. Patients with well-compensated uVDs do not report distressing postural unsteadiness or an aversive sensation of apparent motion of a visual scene (oscillopsia) or "visual confusion" upon rapid head rotation as do those patients with poorly compensated uVDs. It has been suggested that well-compensated subjects eliminate the subjective sensations associated with retinal slip, which must occur as a result of an inadequate vestibuloocular reflex (VOR), either by restricting head movement to the lesioned side or by blinking during head turns. To test this, subjects stood at the curbside of a busy road with a 180 degrees view of regular, fast-moving traffic, which they scanned in preparation of crossing the road, and their eye and head movements and blinks were measured in this natural situation. Both normals and uVDs generated similar ranges of head position, head velocity and gaze magnitude, and all subjects performed a blink during the gaze saccade. Contrary to the hypothesis, no systematic differences were found between normals and either group of uVDs.