Beau B. Bruce

Update on the pathophysiology and management of idiopathic intracranial hypertension.

Idiopathic intracranial hypertension is a disease of unknown aetiology, typically affecting young obese women, producing a syndrome of increased intracranial pressure without identifiable cause. Despite a large number of hypotheses and publications over the past decade, the aetiology is still unknown. Vitamin A metabolism, adipose tissue as an actively secreting endocrine tissue and cerebral venous abnormalities are areas of active study regarding the pathophysiology of idiopathic intracranial hypertension. There continues to be no evidence based consensus or formal guidelines regarding management and treatment of the disease. Treatment studies show that the diagnostic lumbar puncture is a valuable intervention beyond its diagnostic importance, and that weight management is critical. However, many questions remain regarding the efficacy of acetazolamide, CSF shunting procedures and cerebral transverse venous sinus stenting.

Idiopathic intracranial hypertension in men

Objective: To compare the characteristics of idiopathic intracranial hypertension (IIH) in men vs women in a multicenter study. Methods: Medical records of all consecutive patients with definite IIH seen at three university hospitals were reviewed. Demographics, associated factors, and visual function at presentation and follow-up were collected. Patients were divided into two groups based on sex for statistical comparisons. Results: We included 721 consecutive patients, including 66 men (9%) and 655 women (91%). Men were more likely to have sleep apnea (24% vs 4%, p < 0.001) and were older (37 vs 28 years, p = 0.02). As their first symptom of IIH, men were less likely to report headache (55% vs 75%, p < 0.001) but more likely to report visual disturbances (35% vs 20%, p = 0.005). Men continued to have less headache (79% vs 89%, p = 0.01) at initial neuro-ophthalmologic assessment. Visual acuity and visual fields at presentation and last follow-up were significantly worse among men. The relative risk of severe visual loss for men compared with women was 2.1 (95% CI 1.4–3.3, p = 0.002) for at least one eye and 2.1 (95% CI 1.1–3.7, p = 0.03) for both eyes. Logistic regression supported sex as an independent risk factor for severe visual loss. Conclusion: Men with idiopathic intracranial hypertension (IIH) are twice as likely as women to develop severe visual loss. Men and women have different symptom profiles, which could represent differences in symptom expression or symptom thresholds between the sexes. Men with IIH likely need to be followed more closely regarding visual function because they may not reliably experience or report other symptoms of increased intracranial pressure.

Treatment of Nonarteritic Anterior Ischemic Optic Neuropathy

Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common clinical presentation of acute ischemic damage to the optic nerve. Most treatments proposed for NAION are empirical and include a wide range of agents presumed to act on thrombosis, on the blood vessels, or on the disk edema itself. Others are presumed to have a neuroprotective effect. Although there have been multiple therapies attempted, most have not been adequately studied, and animal models of NAION have only recently emerged. The Ischemic Optic Neuropathy Decompression Trial, the only class I large multicenter prospective treatment trial for nonarteritic anterior ischemic optic neuropathy, found no benefit from surgical intervention. One recent large, nonrandomized controlled study suggested that oral steroids might be helpful for acute NAION. Others recently proposed interventions are intravitreal injections of steroids or anti-vascular endothelial growth factor (anti-VEGF) agents. There are no class I studies showing benefit from either medical or surgical treatments. Most of the literature on the treatment of NAION consists of retrospective or prospective case series and anecdotal case reports. Similarly, therapies aimed at secondary prevention of fellow eye involvement in NAION remain of unproven benefit.

Clinical course of idiopathic intracranial hypertension with transverse sinus stenosis

Objective: Transverse sinus stenosis (TSS) is common in idiopathic intracranial hypertension (IIH), but its effect on the course and outcome of IIH is unknown. We evaluated differences in TSS characteristics between patients with IIH with “good” vs “poor” clinical courses. Methods: All patients with IIH seen in our institution after September 2009 who underwent a high-quality standardized brain magnetic resonance venogram (MRV) were included. Patients were categorized as having a good or poor clinical course based on medical record review. The location and percent of each TSS were determined for each patient, and were correlated to the clinical outcome. Results: We included 51 patients. Forty-six patients had bilateral TSS. The median average percent stenosis was 56%. Seventy-one percent of patients had stenoses >50%. Thirty-five of the 51 patients (69%) had no final visual field loss. Eight patients (16%) had a clinical course classified as poor. There was no difference in the average percent stenosis between those with good clinical courses vs those with poor courses (62% vs 56%, p = 0.44). There was no difference in the percent stenosis based on the visual field grade (p = 0.38). CSF opening pressure was not associated with either location or degree of TSS. Conclusion: TSS is common, if not universal, among patients with IIH, and is almost always bilateral. There is no correlation between the degree of TSS and the clinical course, including visual field loss, among patients with IIH, suggesting that clinical features, not the degree of TSS, should be used to determine management in IIH.

Isolated Third, Fourth and Sixth Cranial Nerve Palsies From Presumed Microvascular Versus Other Causes: A Prospective Study

PURPOSE To estimate the proportion of patients presenting with isolated third, fourth, or sixth cranial nerve palsy of presumed microvascular origin versus other causes. DESIGN Prospective, multicenter, observational case series. PARTICIPANTS A total of 109 patients aged 50 years or older with acute isolated ocular motor nerve palsy. TESTING Magnetic resonance imaging (MRI) of the brain. MAIN OUTCOME MEASURES Causes of acute isolated ocular motor nerve palsy (presumed microvascular or other) as determined with early MRI and clinical assessment. RESULTS Among 109 patients enrolled in the study, 22 had cranial nerve III palsy, 25 had cranial nerve IV palsy, and 62 had cranial nerve VI palsy. A cause other than presumed microvascular ischemia was identified in 18 patients (16.5%; 95% confidence interval, 10.7-24.6). The presence of 1 or more vasculopathic risk factors (diabetes, hypertension, hypercholesterolemia, coronary artery disease, myocardial infarction, stroke, and smoking) was significantly associated with a presumed microvascular cause (P = 0.003, Fisher exact test). Vasculopathic risk factors were also present in 61% of patients (11/18) with other causes. In the group of patients who had vasculopathic risk factors only, with no other significant medical condition, 10% of patients (8/80) were found to have other causes, including midbrain infarction, neoplasms, inflammation, pituitary apoplexy, and giant cell arteritis (GCA). By excluding patients with third cranial nerve palsies and those with GCA, the incidence of other causes for isolated fourth and sixth cranial nerve palsies was 4.7% (3/64). CONCLUSIONS In our series of patients with acute isolated ocular motor nerve palsies, a substantial proportion of patients had other causes, including neoplasm, GCA, and brain stem infarction. Brain MRI and laboratory workup have a role in the initial evaluation of older patients with isolated acute ocular motor nerve palsies regardless of whether vascular risk factors are present.

Racial Differences in Idiopathic Intracranial Hypertension

Objective: To evaluate racial differences in idiopathic intracranial hypertension (IIH). Methods: Medical records of all consecutive patients with definite IIH seen between 1989 and 2006 were reviewed. Demographics, associated factors, and visual function at presentation and follow-up were collected. Black patients were compared to non-black patients. Results: We included 450 patients (197 black, 253 non-black). Obesity, systemic hypertension, anemia, and sleep apnea were more common in black patients than in non-black patients (p ≤ 0.01). CSF opening pressure was higher in black patients (40 vs 34 cm CSF, p < 0.001). Visual acuity, visual field loss, and degree of papilledema at presentation and follow-up were worse in black patients (p ≤ 0.01). Diagnostic and therapeutic measures were similar between black patients and non-black patients, except for optic nerve sheath fenestration (p = 0.01) and lumbar puncture (p = 0.03), both more commonly performed on black patients. The relative risk of severe visual loss for black patients compared with non-black patients was 3.5 (95% CI 2.0 to 5.8, p < 0.001) in at least one eye and 4.8 (95% CI 2.1 to 10.9, p < 0.001) in both eyes. Logistic regression analysis supported race, anemia, body mass index, and male gender as independent risk factors for severe visual loss and suggested that racial differences may be partially accounted for by differences in CSF opening pressure, body mass index, and frequency of anemia. Conclusion: Black patients with idiopathic intracranial hypertension (IIH) were more likely than non-black patients with IIH to have severe visual loss in at least one eye. This difference did not appear to result from diagnosis, treatment, or access to care, but may partially relate to differences in other risk factors. Black patients have a more aggressive disease and may need closer follow-up and lower thresholds for early intervention. GLOSSARY: BMI = body mass index; IIH = idiopathic intracranial hypertension.

Nonmydriatic digital ocular fundus photography on the iPhone 3G: the FOTO-ED study.

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Feasibility of nonmydriatic ocular fundus photography in the emergency department: Phase I of the FOTO-ED study.

OBJECTIVES Examination of the ocular fundus is imperative in many acute medical and neurologic conditions, but direct ophthalmoscopy by nonophthalmologists is underutilized, poorly performed, and difficult without pharmacologic pupillary dilation. The objective was to examine the feasibility of nonmydriatic fundus photography as a clinical alternative to direct ophthalmoscopy by emergency physicians (EPs). METHODS Adult patients presenting to the emergency department (ED) with headache, acute focal neurologic deficit, diastolic blood pressure ≥ 120 mm Hg, or acute visual change had ocular fundus photographs taken by nurse practitioners using a nonmydriatic fundus camera. Photographs were reviewed by a neuroophthalmologist within 24 hours for findings relevant to acute ED patient care. Nurse practitioners and patients rated ease, comfort, and speed of nonmydriatic fundus photography on a 10-point Likert scale (10 best). Timing of visit and photography were recorded by automated electronic systems. RESULTS A total of 350 patients were enrolled. There were 1,734 photographs taken during 230 nurse practitioner shifts. Eighty-three percent of the 350 patients had at least one eye with a high-quality photograph, while only 3% of patients had no photographs of diagnostic value. Mean ratings were ≥ 8.7 (standard deviation [SD] ≤ 1.9) for all measures. The median photography session lasted 1.9 minutes (interquartile range [IQR] = 1.3 to 2.9 minutes), typically accounting for less that 0.5% of the patients total ED visit. CONCLUSIONS Nonmydriatic fundus photography taken by nurse practitioners is a feasible alternative to direct ophthalmoscopy in the ED. It is performed well by nonphysician staff, is well-received by staff and patients, and requires a trivial amount of time to perform.

Idiopathic Intracranial Hypertension: Relation Between Obesity and Visual Outcomes

Background:Increased body mass index (BMI) has been associated with increased risk of idiopathic intracranial hypertension (IIH), but the relationship of BMI to visual outcomes in IIH is unclear. Methods:A retrospective chart review of all adult cases of IIH satisfying the modified Dandy criteria seen at our institution between 1989 and 2010 was performed. Demographics, diagnostic evaluations, baseline visit and last follow-up examination data, treatment, and visual outcome data were collected in a standardized fashion. Groups were compared, and logistic regression was used to evaluate the relationship of BMI to severe visual loss, evaluating for interaction and controlling for potential confounders. Results:Among 414 consecutive IIH patients, 158 had BMI ≥40 (World Health Organization Obese Class III) and 172 had BMI 30–39.9. Patients with BMI ≥40 were more likely to have severe papilledema at first neuro-ophthalmology encounter than those with a lower BMI (P = 0.02). There was a trend toward more severe visual loss in 1 or both eyes at last follow-up among those patients with BMI ≥40 (18% vs 11%, P = 0.067). Logistic regression modeling found that 10-unit (kilogram per square meter) increases in BMI increased the odds of severe visual loss by 1.4 times (95% confidence interval, 1.03–1.91, P = 0.03) after controlling for sex, race, diagnosed hypertension, and diagnosed sleep apnea. Conclusion:Our finding of a trend for severe papilledema and visual loss associated with increasing BMI suggests that very obese IIH patients should be closely monitored for progression of visual field loss.

Brain Imaging in Idiopathic Intracranial Hypertension.

Background: The primary role of brain imaging in idiopathic intracranial hypertension (IIH) is to exclude other pathologies causing intracranial hypertension. However, subtle radiologic findings suggestive of IIH have emerged with modern neuroimaging. This review provides a detailed description of the imaging findings reported in IIH and discusses their possible roles in the pathophysiology and the diagnosis of IIH. Evidence Acquisition: References were identified by searches of PubMed from 1955 to January 2015, with the terms “idiopathic intracranial hypertension,” “pseudotumor cerebri,” “intracranial hypertension,” “benign intracranial hypertension,” “magnetic resonance imaging,” “magnetic resonance venography,” “computed tomography (CT),” “CT venography,” “imaging,” and “cerebrospinal fluid (CSF) leak.” Additional references were identified by hand search of relevant articles. When possible, we extracted the number of patients and control subjects from each study for each radiological finding. When at least 2 studies used the same criteria to define a radiological finding, all patients from these studies were pooled to obtain a mean sensitivity and specificity with 95% confidence interval. Results: Specific neuroimaging findings may suggest long-standing IIH, including empty sella, flattening of the posterior globes, optic nerve head protrusion, distention of the optic nerve sheaths, tortuosity of the optic nerve, cerebellar tonsillar herniation, meningoceles, CSF leaks, and transverse venous sinus stenosis. Conclusion: Although IIH remains a diagnosis of exclusion, the most recently proposed diagnostic criteria have included neuroimaging findings to suggest IIH when major diagnostic criteria are not fulfilled. However, these findings are not diagnostic of IIH, and their presence is not required for the diagnosis of definite IIH. Their incidental discovery on brain imaging should not prompt invasive procedures, unless other signs of IIH, such as papilledema, are present.