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.

Pain in ischaemic ocular motor cranial nerve palsies.

AIM: Pain is a common feature of microvascular ischaemic ocular motor cranial nerve palsies (MP). The natural history of pain in this condition has not been studied. The purpose of this report is to define the spectrum of pain in isolated MP, with special reference to diabetic versus non-diabetic patients. DESIGN AND METHODS: Retrospective and prospective chart review was performed on 87 patients with acute-onset MP of a single cranial nerve (CN III, oculomotor; CN IV, trochlear; CN VI, abducens) that progressively improved or resolved over 6 months. RESULTS: Five of the 87 patients had two events, making the total number events 92. There were 39 (42.4%) CN III palsies, five (5.4%) CN IV palsies and 48 (52.2%) CN VI palsies. Thirty-six (41%) patients had diabetes. Pain was present in 57 (62%) events. The majority of diabetic and non-diabetic patients had pain. Pain preceded diplopia by 5.8 (SD 5.5) days in one-third of events. There was a trend towards greater pain with CN III palsies, but this was not statistically significant. Patients who experienced severe pain tended to have pain for a longer duration (26.4 (SD 21.7) days compared with 10.8 (SD 8.3) and 9.5 (SD 9) days for mild and moderate pain, respectively). There was no correlation between having diabetes and experiencing pain. CONCLUSIONS: The majority of MP are painful, regardless of the presence or absence of diabetes. Pain may occur prior to or concurrent with the onset of diplopia. Non-diabetic and diabetic patients presented with similar pain characteristics, contrary to the belief that diabetic patients have more pain associated with MP.

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.

Chronic ataxic neuropathy mimicking dorsal midbrain syndrome.

We describe the clinical course, with special attention to the disturbance of eye movements, of a 29-year-old man with chronic ataxic neuropathy with ophthalmoplegia, IgM paraprotein, cold agglutinins and anti-GD1b disialosyl antibodies (CANOMAD). Using the magnetic search coil technique, we documented convergence during upward saccades and other features suggestive of dorsal midbrain syndrome. Thus, in common with Miller Fisher syndrome, CANOMAD may present with clinical findings implicating involvement of the central nervous system, which contains ganglioside antigens to anti-GD1b antibodies.

Nonarteritic anterior ischemic optic neuropathy with macular edema: visual improvement and fluorescein angiographic characteristics.

The objective of the study was to assess visual outcomes in patients who have nonarteritic anterior ischemic optic neuropathy (NAION) with macular edema (ME). Thirteen eyes (12 patients) with NAION and ME were observed for an average of 5.3 months after onset of visual loss. Intravenous fluorescein angiography was performed on 10 eyes. Fluorescein leakage was observed in 8 of 10 (80%) eyes. Leakage was nonfocal, minimal, and diffuse. Eleven of 13 (85%) eyes with ME improved. The average improvement was 2.3 Snellen lines. The presence of ME in patients with NAION may confer a better visual prognosis than reported in patients with NAION alone.

An approach to acquired visual loss in adults.

This article has covered the fundamentals of evaluating visual loss. These include a careful history and attention to the "vital signs" of neuro-ophthalmology: visual acuities, visual field results, and pupillary reactions.

Unsatisfactory treatment of acquired nystagmus with retrobulbar injection of botulinum toxin.

PURPOSE: We quantified the effects of botulinum toxin injected into the retrobulbar space of patients with acquired nystagmus with prominent vertical or torsional components. METHODS: We measured binocular eye rotations in three planes before and after injection of botulinum toxin (10, 12.5, or 25 units) into the retrobulbar space of one eye of each of three patients, ages 28 to 37 years, with acquired pendular nystagmus. RESULTS: Retrobulbar injection of botulinum toxin abolished or reduced all components of the nystagmus in the treated eye in all three patients for about two to three months. The patient who received 25 units developed complete external ophthalmoplegia and blepharoptosis. The other two patients retained some voluntary movements but developed diplopia. In one patient, visual acuity improved from Jaeger 5 to Jaeger 1. In a second patient, filamentary keratitis developed, and visual acuity declined from Jaeger 2 to Jaeger 7; keratitis was a recurrent problem one year after the botulinum toxin injection. In the third patient with predominantly torsional nystagmus, visual acuity was unchanged at Jaeger 2. No patient was pleased with the results, because of blepharoptosis, diplopia, or discomfort (from keratitis), and none elected to repeat the procedure. CONCLUSIONS: The side effects of botulinum toxin administered by retrobulbar injection limit its therapeutic value in the treatment of acquired nystagmus. Even smaller doses that do not abolish nystagmus may produce troublesome diplopia.

Dynamic properties of the human vestibulo-ocular reflex during head rotations in roll.

We investigated the dynamic properties of the human vestibulo-ocular reflex (VOR) during roll head rotations in three human subjects using the magnetic search coil technique. In the first of two experiments, we quantify the behavior of the ocular motor plant in the torsional plane. The subject's eye was mechanically displaced into intorsion, extorsion or abduction, and the dynamic course of return of the eye to its resting position was measured. The mean predominant time constants of return were 210 msec from intorsion, 83 msec from extorsion, and 217 msec from abduction, although there was considerable variability of results from different trials and subjects. In the second experiment, we quantify the efficacy of velocity-to-position integration of the vestibular signal. Position-step stimuli were used to test the torsional or horizontal VOR, being applied with subjects heads erect or supine. After a torsional position-step, the eye drifted back to its resting position, but after a horizontal position-step the eye held its new horizontal position. To interpret these responses we used a simple model of the VOR with parameters of the ocular motor plant set to values determined during Exp 1. The time constant of the velocity-to-position neural integrator was smaller (typically 2 sec) in the torsional plane than in the horizontal plane (> 20 sec). No disconjugacy of torsional eye movements was observed. Thus, the dynamic properties of the VOR in roll differ significantly from those of the VOR in yaw, reflecting different visual demands placed on this reflex in these two planes.

Treatment of abnormal eye movements that impair vision: strategies based on current concepts of physiology and pharmacology.

Certain abnormal eye movements, especially pathological nystagmus, degrade vision and cause illusory motion of the seen environment. These symptoms are due to excessive movement of images of stationary objects on the retina. Recently, the pathophysiology underlying several types of nystagmus and saccadic oscillations was better defined by the development of animal models and by experimental pharmacological studies. Despite this, few reliable therapies are currently available for these abnormal eye movements. In clinical studies, a number of drugs reportedly helped individual patients, but few drugs have been subjected to double-blind trials. An alternative approach to pharmacological suppression of abnormal eye movements is optical stabilization of images on the retina, which is helpful in selected patients. Weakening of the extraocular muscles, using botulinum toxin or surgery, is prone to cause diplopia and may induce plastic-adaptive changes that render the effect temporary. In some patients, treatment of an underlying condition, such as the Arnold-Chiari malformation, reduces nystagmus and improves vision. There is a need for multicenter trials to evaluate systematically potential treatments of abnormal eye movements that impair vision.

Effectiveness of botulinum toxin administered to abolish acquired nystagmus.

We injected botulinum toxin into the horizontal rectus muscles of the right eyes of 2 patients who had acquired pendular nystagmus with horizontal, vertical, and torsional components. This treatment successfully abolished the horizontal component of the nystagmus in the injected eye in both patients for approximately 2 months. Both patients showed a small but measurable improvement of vision in the injected eye that may have been limited by coexistent disease of the visual pathways. The vertical and torsional components of the nystagmus persisted in both patients. In 1 patient, the horizontal component of nystagmus in the noninjected eye increased; we ascribe this finding to plastic-adaptive changes in response to paresis caused by the botulinum toxin. Such plastic-adaptive changes and direct side effects of the injections--such as diplopia and ptosis--may limit the effectiveness of botulinum toxin in the treatment of acquired nystagmus. Neither patient elected to repeat the botulinum treatment.

Absence of the relative afferent pupillary defect with monocular temporal visual field loss.

We report five patients with monocular temporal visual field abnormalities who did not have clinically detectable relative afferent pupillary defects. The causes for the field defects were posterior ischemic optic neuropathy, craniopharyngioma, pituitary adenoma, pseudotumor cerebri, and traumatic optic neuropathy. We discuss the possible explanations for our observations, considering the known anatomy of the pregeniculate visual pathways and the afferent pupillary pathways.

Rapid response of syphilitic optic neuritis to posterior sub-tenon's steroid injection.

An HIV-positive man with subacute syphilitic meningitis developed severe bilateral visual loss from optic neuritis. His visual acuity improved remarkably within 24 hours after single posterior sub-Tenon's injections of triamcinolone (Kenalog) were given. Periocular steroid injections should be considered as an adjunctive treatment of syphilitic optic neuritis.

Superior oblique myokymia. Quantitative characteristics of the eye movements in three patients.

Using the magnetic search coil technique, we measured horizontal, vertical, and torsional rotations of both eyes of two patients with idiopathic superior oblique myokymia, and of the affected eye in a third patient. Superior oblique myokymia was strictly monocular and consisted of an initial intorsion and depression of the affected eye and subsequent oscillations with torsional and vertical components. The peak-to-peak torsional and vertical amplitudes of the oscillations were less than 1 degree, but peak velocities frequently exceeded 4 degrees/sec in both planes. Fourier analysis indicated two features: (1) a broad range of frequencies up to about 50 Hz, indicating irregular oscillations; and (2) a superimposed larger-amplitude oscillation in the range from 1.5 to 6 Hz. Taken with electromyographic data from other studies, these results indicate that superior oblique myokymia reflects spontaneous discharge of trochlear motor neurons that have undergone regenerative changes.

Superficial temporal artery biopsy. A simplified technique.

A simplification of the method for superficial temporal artery biopsy is presented. The main trunk of the artery is taken preferentially because of its more constant anatomic location. An improvement in the technique for performing the subcutaneous dissection is also discussed.

Alternating sequential intracarotid BCNU and cisplatin in recurrent malignant glioma.

The authors entered 43 patients with recurrent malignant glioma in a trial of alternating sequential intracarotid BCNU and cisplatin. Protocol design was alternating courses of BCNU (2 doses, 300 to 400 mg each) and cisplatin (2 doses, 150 to 200 mg each) each at 4-week to 6-week intervals. Eight of 40 patients (20%) evaluable after the first course of BCNU showed partial or minor response. Only 18 patients were evaluable after the first course of cisplatin, and 5 were evaluable after the second course of BCNU. Median survival was 9 months (range, 2 weeks to 6 years). Cerebral or ocular toxicity unique to this method of chemotherapy administration and failure to show clinical improvement were the most common reasons for removal from study. Because of the high attrition rate, the authors were unable to determine a meaningful response to alternating sequential BCNU and cisplatin or to test the clinical degree of cross-resistance to these agents in human malignant glioma.

Ophthalmologic aspects of headache.

Pain around the eye can be caused by local ophthalmic disorders or by disease of other structures sharing trigeminal nerve sensory innervation. In general, most ocular causes for pain also cause the eye to be red, thus alerting the examiner to the focality of the problem. However, conditions like eyestrain, intermittent angleclosure glaucoma or neovascular glaucoma, and low-grade intraocular inflammation can be painful and not be associated with obvious redness. Ocular signs and symptoms also occur with numerous other causes of headache. Double vision in association with periocular pain can result from orbital lesions, isolated cranial neuropathies, and cavernous sinus lesions. Pupillary abnormalities like Horner's syndrome may result from a variety of painful conditions, including cluster headache, parasellar neoplasms or aneurysms, internal carotid dissection or occlusion, and Tolosa-Hunt syndrome. Pain with a dilated and unreactive pupil may reflect a benign condition like Adie's syndrome or ophthalmoplegic migraine, or it may herald the presence of a life-threatening posterior communicating artery aneurysm. Headache and transient visual loss can be manifestations of classic migraine, or be symptoms of ocular hypoperfusion from ipsilateral internal carotid occlusion or increased intracranial pressure from pseudotumor cerebri. In a young patient, head pain with a fixed visual deficit may result from optic neuritis, in an older adult, temporal arteritis may be the culprit. Ophthalmologic aspects of headache thus encompass problems that range from simple and benign to complex and formidable.