Role of vitamin A metabolism in IIH: Results from the idiopathic intracranial hypertension treatment trial.

INTRODUCTION: Vitamin A and its metabolites (called retinoids) have been thought to play a role in the development of idiopathic intracranial hypertension (IIH). The IIH Treatment Trial (IIHTT) showed the efficacy of acetazolamide (ACZ) in improving visual field function, papilledema grade, quality of life and cerebrospinal fluid (CSF) pressure. We postulated that IIH patients would demonstrate elevated measures of vitamin A metabolites in the serum and CSF. METHODS: Comprehensive measures of serum vitamin A and its metabolites were obtained from 96 IIHTT subjects, randomly assigned to treatment with ACZ or placebo, and 25 controls with similar gender, age and body mass index (BMI). These included retinol, retinol binding protein, all-trans retinoic acid (ATRA), alpha- and beta-carotenes, and beta-cryptoxanthin. The IIHTT subjects also had CSF and serum vitamin A and metabolite measurements obtained at study entry and at six months. RESULTS: At study entry, of the vitamin A metabolites only serum ATRA was significantly different in IIHTT subjects (median 4.33nM) and controls (median 5.04nM, p=0.02). The BMI of IIHTT subjects showed mild significant negative correlations with serum ATRA, alpha- and beta-carotene, and beta-cryptoxanthin. In contrast, the control subject BMI correlated only with serum ATRA. At six months, the serum retinol, alpha-carotene, beta-carotene, and CSF retinol were increased from baseline in the ACZ treated group, but only increases in alpha-carotene (p=0.02) and CSF ATRA (p=0.04) were significantly greater in the ACZ group compared with the placebo group. No other vitamin A measures were significantly altered over the six months in either treatment group. Weight loss correlated with only with the change in serum beta-carotene (r=-0.44, p=0.006) and the change in CSF retinol (r=-0.61, p=0.02). CONCLUSION: Vitamin A toxicity is unlikely a contributory factor in the causation of IIH. Our findings differ from those of prior reports in part because of our use of more accurate quantitative methods and measuring vitamin A metabolites in both serum and CSF. ACZ may alter retinoid metabolism in IIH patients.

Treatment of cerebral aneurysms with hydrogel-coated platinum coils (HydroCoil): early single-center experience.

PURPOSE: The authors report their experience using HydroCoils in the treatment of cerebral aneurysms. METHODS: We performed a retrospective review of the first 100 nonrandomized patients (104 coiled saccular cerebral aneurysms) treated with HydroCoils during a 27-month period. RESULTS: The average percentage of HydroCoil by length detached in treated aneurysms was 45.5% (range, 9.9-100%). Immediate postprocedure angiography demonstrated complete aneurysm occlusion in 34%, neck remnant in 35%, and incomplete occlusion in 32%. Immediate procedure-related morbidity and mortality rates were 5.8% and 0%, respectively. Angiographic follow-up was obtained in 51% (51/100 patients; 53/104 aneurysms; average, 10.3 months; range, 0-31 months). In these 53 angiographically followed aneurysms, the overall recanalization rate was 21%: no recanalization occurred in 23 aneurysms with small size (<10 mm)/small neck (<4 mm) (S/S); 4 recanalizations occurred in 7 aneurysms with small size/wide neck (>4 mm) (S/W); 6 recanalizations (27%) occurred in 22 large (L) aneurysms (>10-25 mm, 70% angiographic follow-up); and 1 giant (G) (>25 mm) aneurysm recanalized. A large proportion of aneurysms that were not initially completely occluded were completely occluded on follow-up (15/43 [35%]). Clinical follow-up was obtained in 73 patients (73%; average, 5.3 months; range, 0-24 months): 93% of these patients were neurologically improved or unchanged. Three patients rehemorrhaged and 3 patients with unruptured aneurysms developed delayed hydrocephalus. CONCLUSIONS: The overall safety profile of HydroCoils appears acceptable. Preliminary midterm observations suggest less coil compaction/aneurysm recanalization in large aneurysms. However, HydroCoil-related delayed hydrocephalus is a concern.

Clinical profile of simultaneous bilateral optic neuritis in adults.

AIM: To establish the clinical profile of simultaneous bilateral optic neuritis in adults, the efficacy of steroid therapy, extent of visual recovery, and neurological outcome. METHODS: The authors performed a retrospective review of records of patients referred to a neuro-ophthalmology service with acute bilateral optic neuritis from 2000-4. Exclusion criteria included previous multiple sclerosis or myelopathy, known systemic disorders or medications associated with optic neuropathy, uveitis, or neoplasm. Patients received intravenous methylprednisolone followed by oral prednisone. Visual acuity (logMAR conversion), mean deviation (dB) for visual fields, percentage of Ishihara plates seen, ophthalmoscopy, and neurological evaluation were recorded at baseline and at 6 months or 12 months. Owing to strong correlation for visual loss between eyes, the results for the worse eye in each patient were analysed. RESULTS: 11 men and four women, with an age range of 18-64 years, had bilateral decreased vision, 12 with pain on eye movement. Except for one patient, no aetiology was found. All patients had normal neurological evaluations, average visual acuity 1.71 (SD 0.55), colour vision 2.7% (SD 9.9%), and mean deviation -25.35 dB (SD -7.95 dB). Both optic nerves showed abnormal signal on magnetic resonance imaging. 14 patients improved and their last average visual acuity, colour vision, and mean deviation were 0.36 (SD 0.54), 69% (SD 46%), and -7.05 dB (SD 8.40 dB), respectively. No patient developed a neurological problem during the follow up with a mean of 11 months. CONCLUSION: Idiopathic acute bilateral optic neuritis without myelopathy occasionally occurs in adults. Vision recovers with corticosteroid therapy and during the first year neurological dysfunction will frequently not occur.

Ocular motor dysfunction and ptosis in ocular myasthenia gravis: effects of treatment.

AIM: The optimal treatment of ocular myasthenia gravis (OMG) remains unknown. The authors evaluated the efficacy of prednisone and pyridostigmine in reducing diplopia, ocular motor dysfunction, and ptosis in patients with OMG. METHODS: Review of records from a clinical database from one neuro-ophthalmology service of patients presenting with OMG between 1990 and 2002, excluding those who developed generalised MG within the first month after diagnosis. Institutional review board approval was obtained for this study. PARTICIPANTS/INTERVENTIONS: Non-randomised, unmasked, therapy was given. 55 patients with diplopia in primary or downward gaze and clinically demonstrable extraocular muscle dysfunction received prednisone. 34 patients who had contraindications to steroids or who refused treatment with prednisone received pyridostigmine only. Over 5 days the daily prednisone dose was increased to 50-60 mg and then gradually reduced to 10 mg, followed by further reduction as tolerated. The pyridostigmine dose was begun at 180 mg daily and increased as tolerated. MAIN OUTCOME MEASURES: Follow up evaluations, performed at 1, 3-6, 12, and 24 months, detailed the frequency of ptosis and diplopia and the amount of ocular motor deviation in primary and downward gaze. RESULTS: The prednisone and pyridostigmine groups were similar for age, sex, acetylcholine receptor antibody level, prism cover test results for primary and downward gaze, diplopia in primary and downward gaze, and unilateral ptosis. Bilateral ptosis was present in 32.4% of the pyridostigmine group and 10.9% of the prednisone group (p = 0.02). The prednisone group showed resolution in primary gaze diplopia, downgaze diplopia, unilateral ptosis, and bilateral ptosis in 73.5%, 75.5%, 85.7%, and 98%, respectively at 1 month. The benefit persisted at 3-6, 12, and 24 months except for the bilateral ptosis. The pyridostigmine group showed resolution in primary gaze diplopia, downgaze diplopia, unilateral ptosis, and bilateral ptosis in 6.9%, 17.2%, 50%, and 76.7% of patients after 1 month of treatment. The prism cover results improved (p = 0.003) in the prednisone group only. In the prednisone group, four patients had no response to therapy. Among the 51 prednisone responsive patients, there were 33 recurrences in 26 patients. 12 patients, all prednisone treated, had remissions. Except for three patients who developed diabetes, no patient developed a clinically significant systemic corticosteroid complication. CONCLUSION: These results suggest that 50-60 mg daily prednisone followed by lower doses (10 mg or less) has the benefit of resolving ptosis and diplopia that lasts for at least 2 years in approximately 70% of patients.

Visual system abnormalities in patients with Parkinson's disease.

Visual evoked potentials (VEPs) and contrast sensitivity measurements were determined in normally sighted patients with Parkinson's disease (PD). Prolonged latencies of the first major positive (P100) wave of the VEP elicited by an alternating vertical grating were noted. The delay in latency was positively correlated with the severity of the movement disability. Subjective testing of contrast thresholds demonstrated significant elevation of thresholds in PD. Electroretinographic oscillatory potentials were elicited to determine if the delay in P100 latency was of retinal origin. No specific lesion could be identified to account for the abnormality in VEP or in contrast testing results.

Beneficial effects of corticosteroids on ocular myasthenia gravis.

OBJECTIVE: To determine if moderate-or low-dose corticosteroid therapy can reduce the diplopia and frequency of deterioration to generalized disease in ocular myasthenia gravis. DESIGN: Retrospective record review. SETTING: Two university-based neuro-ophthalmology services. PATIENTS: All 32 patients with ocular myasthenia gravis, treated with prednisone, followed up for a minimum of 2 years were included. Patients were treated with 1 or more courses of daily prednisone (highest initial dose, 40-80 mg) gradually withdrawn over 4 to 6 weeks. Subsequently, in 6 patients, 2.5 to 20 mg of prednisone was given on alternate day. OUTCOME MEASURES: Diplopia in the primary position or downgaze diplopia and generalized myasthenia gravis after 2 years of follow-up. RESULTS: Diplopia, which was initially found in the primary position in 29 patients and in the downgaze position in 26 patients, was absent in 21 patients at 2 years. Generalized myasthenia gravis occurred in 3 patients at 2 years. Elevated serum acetylcholine receptor antibody levels and abnormal electromyography findings were not predictive of worsening. No patient experienced a major steroid complication. CONCLUSIONS: Moderate-dose daily prednisone for 4 to 6 weeks, followed by low-dose alternate-day therapy as needed, can control the diplopia in patients with ocular myasthenia gravis. The frequency of deterioration to generalized myasthenia gravis at 2 years may be reduced; 9.4% in this study compared with more than 40% previously reported frequency. Corticosteroids may be useful even when ocular motor dysfunction is not normalized.

Visual evoked potentials in chiasmal gliomas in four adults.

Visual evoked potentials (VEPs) were recorded from four patients with surgically verified chiasmal gliomas. Despite good visual acuity, 6/12(20/40) or better in each eye, these patients showed substantially reduced VEP amplitudes to a diffuse flash stimulus and hardly detectable responses to a highly textured checkerboard-pattern stimulus. The dissociation between evoked electrical activity and visual acuity is noteworthy; this differs from previously reported findings in patients with extrinsic compressing lesions of the chiasm or with lesions of demyelinating disease, which usually reduce VEP amplitude and increase conduction time in rough proportion to a loss of visual acuity.

Neuropathy with susceptibility to compression aggravated by herniated disk. Early pathological and electrodiagnostic studies.

We describe a patient with a foot drop attributable to both herniated disk and peripheral neuropathy susceptible to external compression. Early electrodiagnostic studies and sural nerve biopsy indicated a role for myelin dysfunction in this disorder.

Reduced contrast sensitivity in compressive lesions of the anterior visual pathway.

A clinical procedure for determining contrast sensitivity was performed on patients with suspected sella area masses. The test consisted of a series of six plates, each containing a bar pattern of fixed sinusoidal spatial frequency in which contrast varies along the length of the bar. Patients with compressive lesions of the chiasm of optic nerve showed loss of contrast sensitivity over the whole range of spatial frequencies. The general loss in contrast was evident even in patients with 20/20 Snellen acuity. After surgery, contrast sensitivity improved, as did other measures of vision, but significant contrast deficits remained. Contrast sensitivity is a sensitive indicator for the diagnosis and evaluation of compressive lesions of the chiasm.

Optic tract atrophy with cerebral arteriovenous malformations: direct and transsynaptic degeneration.

Three patients with postgeniculate cerebral arteriovenous malformations (AVM) had band atrophy of the contralateral optic nerve. One patient had homonymous hemioptic hypoplasia. These cases might have been construed as demonstrating transsynaptic degeneration across the lateral geniculate nucleus to the anterior visual pathway. However, neuroimaging studies revealed abnormal deep venous drainage remote from the AVM nidus that directly involved the lateral geniculate nucleus and posterior optic tract.

Percutaneous transvascular treatment of giant carotid aneurysms: neuro-ophthalmologic findings.

Twelve of 17 patients with cavernous carotid aneurysms had balloon embolization directed through a percutaneous double lumen catheter for progressive pain, ophthalmoplegia, or visual loss. Functional angiography was carried out with systemic heparinization and double-lumen balloon catheters to test tolerance to carotid occlusion. Eleven were successfully treated, though two patients with initial preservation of the ipsilateral carotid artery had unplanned deflation of the balloon, necessitating re-embolization. No serious permanent neurologic complications occurred. All patients had complete resolution of pain, and nine had improvement in the extraocular eye muscle and lid function. Balloon trapping of the cavernous carotid artery, rather than placing the balloon directly into the aneurysm, resulted in involution of the aneurysm and decompression of the involved cranial nerves.

The 20/20 eye in multiple sclerosis.

Using clinical and electrophysiologic measures, we evaluated the visual pathway of patients who had multiple sclerosis, 20/20 Snellen acuity, and no history of optic neuritis. Delayed latencies were found in the transient visual evoked potentials (VEPs) of 38% of the patients, and interocular latency differences were abnormal in 67%. Contrast VEPs were abnormal in 46%. Psychophysical determinations of contrast sensitivity were abnormal in 78%. Only 17% of the patients had dyschromatopsia, 36% had afferent pupillary abnormalities, and 59% had optic nerve pallor or nerve fiber layer loss. Psychophysical contrast evaluations and VEP studies were superior to other clinical evaluations in demonstrating visual dysfunction in these patients.

Bilateral orbital signs predict cortical venous drainage in cavernous sinus dural AVMs.

BACKGROUND: Most cavernous sinus dural arteriovenous malformations (CSdAVM) have a benign clinical course. Those CSdAVM that drain into cortical veins have an increased risk for neurologic complications. OBJECTIVE: To find whether a specific clinical sign predicts cortical venous drainage (CVD) in CSdAVM. METHODS: The records of 118 patients with CSdAVM were evaluated for the clinical features of the disorder and tested for predictive value of CVD demonstrated angiographically or suggested by MRI using logistic regression and odds ratio (OR) analysis. RESULTS: Clinical signs that predicted the presence of CVD included bilateral orbital signs (p = 0.004, OR = 23.84) and presence of a postauricular bruit (p = 0.035, OR = 23.8). No other clinical sign predicted the presence of CVD, including extraocular muscle dysfunction, abducens or oculomotor dysfunction, increased intraocular pressure, venous stasis retinopathy, choroidal effusion, optic neuropathy, subjective bruit, and objective orbital bruit. CONCLUSION: Patients who present with or develop bilateral orbital congestion should be recognized as being at increased risk for CVD.

Unilateral swollen disc due to increased intracranial pressure.

Truly unilateral papilledema is rare and poses a diagnostic problem. The authors have prospectively looked for patients with truly unilateral papilledema and found 15 patients, 10 of whom had idiopathic intracranial hypertension. Neuroimaging did not indicate a reason for the lack of swelling in the other nerve. The visual deficits and outcomes were similar to those of patients with bilateral papilledema. Although monocular papilledema is uncommon, a lumbar puncture with opening pressure measurement should be considered.

Effects of weight loss on the course of idiopathic intracranial hypertension in women.

OBJECTIVE: To determine the role of weight loss in the treatment of idiopathic intracranial hypertension (IIH) in obese women. METHODS: Chart review of 250 patients with suspected IIH revealed 58 women who met our criteria, did not undergo early surgical intervention, and had adequate documentation of visual status, papilledema, and weight at the baseline evaluation and at 6 months or longer. Patients were divided into two groups based on whether weight loss > or = 2.5 kg occurred during any 3-month interval. Papilledema grade, visual acuity, and visual field grade at 6 months or longer and the time to improve each were recorded. RESULTS: Mean time in months to improve one grade for papilledema and visual field in one eye was 4.0 versus 6.7 (p = 0.013) and 4.6 versus 12.2 (p = 0.032), respectively, for the 38 patients with weight loss compared with the 20 patients with no weight loss. Papilledema resolved in 28/38 with weight loss (mean, 7.6 months) and 8/20 without weight loss (mean, 10.2 months; p = 0.352). There were no differences in final visual acuity or visual field between the two groups, but the papilledema grade was slightly better in the worst eye in each patient at baseline in the weight loss group (p = 0.03). CONCLUSIONS: Weight reduction is associated with more rapid recovery of both papilledema and visual field dysfunction in patients with IIH compared with those who do not lose weight.

Visual symptoms with dural arteriovenous malformations draining into occipital veins.

OBJECTIVE: To determine the cause of the visual dysfunction and effect of treatment on dural arteriovenous malformations (DAVMs) that secondarily involve the occipital lobe. BACKGROUND: DAVMs are an infrequent cause of visual dysfunction that should be amenable to treatment if diagnosed before permanent visual field loss. METHODS: The records of seven patients with cerebral visual disturbances associated with DAVMs were analyzed with attention to visual symptoms, visual field testing, and vascular anatomy. RESULTS: Sudden visual loss occurred in five patients, two with a hemorrhage and one with a venous infarct in the occipital lobe. Fortification images occurred in three patients, two of whom had palinopsia (one with de novo formed visual hallucinations). Homonymous quadrantic or hemianoptic field defects, some fluctuating, were found in six patients. Angiography revealed each DAVM was supplied solely by dural arteries and drained into occipital pial veins due to retrograde blood flow through the sites near or in the wall or lumen of the dural venous channels that normally drain the occipital lobe. Unlike DAVMs in other locations, only two patients had occlusion of an adjacent venous sinus. These patients, particularly the two with posterior fossa DAVMs remote to the occipital lobe, clearly demonstrate the visual and neurologic dysfunction resulting from venous hypertension. In six patients, intra-arterial embolization of the arterial feeders and nidus (one patient required additional surgery) resulted in resumption of normal occipital venous emptying. No further visual episodes occurred in five of these six patients. The visual fields normalized in three patients and improved in one with venous infarct but were unchanged in both patients with a hemorrhage. CONCLUSIONS: DAVMs that drain into occipital veins cause field loss and other visual disturbances because of venous hypertension in the occipital lobe, which can be reversed by occluding the DAVM nidus. If a venous infarct or hemorrhage has not caused irreversible damage, visual recovery should be complete.

Occipital arteriovenous malformations: visual disturbances and presentation.

BACKGROUND: Occipital arteriovenous malformations (AVMs) cause a variety of visual disturbances and headaches. Early diagnosis may lead to treatment that reduces the risk of hemorrhages, visual field loss and other neurologic deficits, and death. METHODS: We reviewed the records of the 70 patients with occipital AVMs referred to New York University Medical Center to investigate the mode of presentation and the outcome of treatment. RESULTS: Sixty-eight patients presented with one or more symptoms, including homonymous visual disturbances in 39, headache in 39, seizures in 20, and hemorrhage in twenty-six. Visual field loss was more common (p = 0.0007) and more severe (p = 0.0002) in patients who bled than in those with unruptured AVMs (16/44). The frequency of visual field loss was not associated with calcarine artery supply to the AVM. Prior to treatment, the fields improved in five patients with visual loss associated with a hemorrhage. Forty-six patients were treated with embolization, surgery, radiosurgery, or a combination of therapies. The AVM was eliminated in 19 of 20 patients (nine with preoperative partial embolization) treated with surgery versus in 4 of 27 patients treated only with embolization. There were two AVM-associated deaths, two subarachnoid hemorrhages, and four new neurologic deficits after treatment. Visual fields were worse in 15 patients, unchanged in 22, and improved in eight. CONCLUSIONS: Whereas some features of headache and visual symptoms are similar for occipital AVMs and migraine, the two disorders are usually distinguishable. Visual field improvement can spontaneously occur in patients who have had loss secondary to an intracerebral bleed. Treatment with embolization or surgery, particularly with surgical excision of the AVM, can result in new or worse visual field loss.

Visual system toxicity following intra-arterial chemotherapy.

We studied the effects of intra-arterial chemotherapy on the visual system of 29 consecutive patients with gliomas. As expected, infra-ophthalmic carotid infusion of cisplatin or carmustine (BCNU) was associated with clinically apparent anterior visual pathway lesions. Electroretinography revealed retinal dysfunction in patients without clinical abnormalities. Supra-ophthalmic carotid infusion of cisplatin or BCNU caused no retinal or optic nerve lesions. Electroretinography was abnormal in only one of these patients. Our results indicated that BCNU and cisplatin cause ischemic damage and are toxic to both retinal and neural tissue in patients with gliomas.

The assessment of evoked potential contrast thresholds using real-time retrieval.

Electrophysiologic contrast sensitivity functions (CSF) have been estimated using lock-in amplifier signal retrieval of the visually evoked response (VER). These CSFs were compared with CSFs obtained psychophysically using the same stimulus conditions. The two measures of contrast sensitivity behave similarly in response to variations of temporal and spatial frequency. The major advantage of using real-time retrieval is speed. Threshold for a single spatiotemporal condition can be estimated in as little as 20 sec, making the application of electrophysiologic contrast sensitivity testing feasible for clinical populations.

Contrast sensitivity loss in multiple sclerosis. Selectivity by eye, orientation, and spatial frequency measured with the evoked potential.

Multiple sclerosis can produce highly selective losses in visual function. Psychophysical studies have demonstrated contrast sensitivity deficits for spatial frequencies or for stimulus orientations. Using real-time lock-in retrieval of the visual evoked potential, the authors measured contrast sensitivity in 15 cases with probable or definite multiple sclerosis and acuities of 20/40 or better. Sine-wave grating contrast threshold determinations for three spatial frequencies (1, 4, and 8 cycles/deg) and four orientations (0, 45, 90, and 135 deg) revealed contrast deficits in at least one spatial frequency and orientation in every case. In most cases the visual losses were spotty or multifocal, and not the same in both eyes. Some cases with highly selective patterns of orientation or spatial frequency losses were observed and are discussed in terms of involvement of cortical functional architecture in the disease.