Matthew J. Thurtell

Transverse Sinus Stenting for Idiopathic Intracranial Hypertension: A Review of 52 Patients and of Model Predictions

Current thinking is that transverse sinus stenosis with significant pressure gradient across the narrowing may play a role in pseudotumor cerebri and that treatment may improve symptoms. Here, the authors review their experience with 52 patients who were clinically followed for 2–8 months after stenting. During this time all pressure gradients improved and symptoms were abolished. Symptom relapse occurred in 6 patients and all showed sinus restenosis. At the end of the study period, 49 of 52 patients were cured of their headaches and the authors concluded that transverse sinus stenting is beneficial in this clinical setting. 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 H20) with a mean transverse sinus stenosis gradient of 20 mm Hg. The mean lumbar CSF pressure before stent placement was 322 mm H2O. 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.

Pharmacotherapy of vestibular and ocular motor disorders, including nystagmus

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.

Eye movements in amyotrophic lateral sclerosis and its mimics: a review with illustrative cases

Abnormal eye movements are increasingly recognised in patients with amyotrophic lateral sclerosis (ALS) and, when they occur, may provide insights into the pattern and pathogenesis of the disease process. In patients with disorders that mimic ALS, abnormal eye movements may point to the correct diagnosis. In both of these circumstances, systematic examination of eye movements and interpretation of the findings with reference to modern concepts of their neural substrate will aid diagnosis and suggest pathogenesis. Here, key points with illustrative case histories and eye movement records are highlighted.

Crossover trial of gabapentin and memantine as treatment for acquired nystagmus

We conducted a masked, crossover, therapeutic trial of gabapentin (1,200mg/day) versus memantine (40mg/day) for acquired nystagmus in 10 patients (aged 28–61 years; 7 female; 3 multiple sclerosis [MS]; 6 post‐stroke; 1 post‐traumatic). Nystagmus was pendular in 6 patients (4 oculopalatal tremor; 2 MS) and jerk upbeat, hemi‐seesaw, torsional, or upbeat‐diagonal in each of the others. For the group, 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 1 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. ANN NEUROL 2010;67:676–680

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°), high‐velocity (150‐350°/s), high‐acceleration (4000‐6000°/s2), 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.

Neuro-ophthalmology of invasive fungal sinusitis: 14 consecutive patients and a review of the literature

Invasive fungal sinusitis is a rare condition that usually occurs in immunocompromised patients and often presents as an orbital apex syndrome. It is frequently misdiagnosed on presentation and is almost always lethal without early treatment.

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.

The Berlin questionnaire screens for obstructive sleep apnea in idiopathic intracranial hypertension.

Background Obstructive sleep apnea (OSA) may be associated with idiopathic intracranial hypertension (IIH), a disorder most commonly occurring in young obese women. Because polysomnography, the standard test for diagnosing OSA, is expensive and time consuming, questionnaires have been developed to identify persons with OSA. The Berlin questionnaire (BQ) reliably identifies middle-aged and older persons in the community who are at high-risk for OSA. We aimed to validate the BQ as a screening tool for OSA in IIH patients. Methods Patients with newly diagnosed IIH completed the BQ and then underwent diagnostic polysomnography. The BQ was scored as high or low risk for OSA, and the diagnosis of OSA was based on polysomnography findings. OSA was defined as an apnea-hypopnea index of ≥5 on polysomnography. Results Thirty patients were evaluated (24 women; 15 white and 15 black; age, 16–54 years [median, 32 years]; body mass index, 27.3–51.7 kg/m2 [median, 39.8 kg/m2]). Twenty patients (66.7%) had a high-risk BQ score and 18 (60%) exhibited OSA. Fifteen of 20 (75%) with a high-risk BQ score had OSA, while 3 of 10 (30%) with a low-risk score had OSA (Fisher test, P = 0.045). The sensitivity and specificity of the BQ for OSA in IIH patients were 83% and 58%, respectively, whereas the positive predictive value was 75%. Conclusion A low-risk BQ score identifies IIH patients who are unlikely to have OSA. Polysomnography should be considered in those with a high-risk score.

Complete Ophthalmoplegia: An Unusual Sign of Bilateral Paramedian Midbrain-Thalamic Infarction

Background and Purpose— Complete ophthalmoplegia, the combination of bilateral ptosis with loss of all extraocular movements, is rarely a consequence of ischemic stroke. We describe 3 patients who had complete ophthalmoplegia as a manifestation of bilateral paramedian midbrain-thalamic infarction, and we discuss possible pathophysiologic mechanisms. Summary of Cases— Three patients presented with coma. All had complete ophthalmoplegia that initially persisted despite improvement or fluctuation in their other deficits. MRI revealed bilateral paramedian midbrain-thalamic infarction. Two patients died, with the ophthalmoplegia remaining unchanged before death. The surviving patient had a progressive improvement in ocular abduction but persisting third nerve and vertical gaze palsies. Conclusions— Complete ophthalmoplegia is an unusual sign of bilateral paramedian midbrain-thalamic infarction. The ophthalmoplegia could result from combined third nerve, pseudoabducens, and vertical gaze palsies.

Neurological Basis for Eye Movements of the Blind

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.