Clinical Predictors of Pulsatile Tinnitus in Patients With Idiopathic Intracranial Hypertension: An Age-Matched Cohort Study.

INTRODUCTION: Pulsatile tinnitus (PT) occurs in many but not all patients with idiopathic intracranial hypertension (IIH). It is poorly understood why some patients with IIH develop PT, yet others do not. The purpose of this study was to determine if any clinical findings differ between those with and without PT in IIH, potentially shedding light on a pathophysiologic mechanism. METHODS: Age-matched cohort analysis of patients with documented IIH and presence or absence of PT was performed, collecting data including body mass index (BMI), blood pressure, visual acuity, cerebrospinal fluid (CSF) opening pressure, sleep apnea, migraines, and transient visual obscurations, among others. Independent-sample t test and χ2 test were used to analyze continuous and binary variables, respectively, with multivariate analysis conducted including variables statistically significant on univariate analysis. RESULTS: Eighty subjects with IIH met the inclusion criteria (40 PT+, 40 PT-). CSF opening pressure showed no significant difference between the two groups. The PT+ cohort was found to have an average BMI of 45.1 kg/m 2 , which was significantly higher than the PT- group (37.7 kg/m 2 ; p = 0.0023). PT+ pulse pressure (60.1 mm Hg) was also significantly higher than the PT- group (51.6 mm Hg; p = 0.019). PT+ patients were also significantly more likely to have sleep apnea ( p < 0.001) and migraines ( p = 0.0036). Multiple logistic regression revealed an adjusted odds ratio of 13.9 for sleep apnea, 4.1 for migraines, and 1.01 for every increase in unit of BMI. CONCLUSION: Among patients with IIH, presence of PT is associated with higher BMI and pulse pressure, and increased incidence of sleep apnea and migraines. Given no significant difference in CSF pressures between the two groups, PT may not be a product of increased disease severity but may be related to sequelae of obesity, such as increased pulse pressure and sleep apnea.

Neuro-Ophthalmic Complications in Patients Treated With CTLA-4 and PD-1/PD-L1 Checkpoint Blockade.

BACKGROUND: In recent years, CTLA-4 and PD-1/PD-L1 checkpoint inhibitors have proven to be effective and have become increasingly popular treatment options for metastatic melanoma and other cancers. These agents work by enhancing autologous antitumor immune responses. Immune-related ophthalmologic complications have been reported in association with checkpoint inhibitor use but remain incompletely characterized. This study seeks to investigate and further characterize the neuro-ophthalmic and ocular complications of immune checkpoint blockade treatment. METHODS: A survey was distributed through the secure electronic data collection tool REDCap to neuro-ophthalmology specialists in the North American Neuro-Ophthalmology Society listserv. The study received human subjects approval through the University of California at Los Angeles Institutional Review Board. The survey identified patients sent for neuro-ophthalmic consultation while receiving one or more of a PD-1 inhibitor (pembrolizumab, nivolumab, or cemiplimab); PD-L1 inhibitor (atezolizumab, avelumab, or durvalumab); or the CTLA-4 inhibitor ipilimumab. Thirty-one patients from 14 institutions were identified. Patient demographics, neuro-ophthalmic diagnosis, diagnostic testing, severity, treatment, clinical response, checkpoint inhibitor drug used, and cancer diagnosis was obtained. RESULTS: The checkpoint inhibitors used in these patients included pembrolizumab (12/31), nivolumab (6/31), combined ipilimumab with nivolumab (7/31, one of whom also received pembrolizumab during their course of treatment), durvalumab (3/31), ipilimumab (2/31), and cemiplimab (1/31). Malignant melanoma (16/31) or nonsmall cell lung carcinoma (6/31) were the most common malignancies. The median time between first drug administration and the time of ophthalmological symptom onset was 14.5 weeks. Eleven patients had involvement of the optic nerve, 7 patients had inflammatory orbital or extraocular muscle involvement, 6 patients had ocular involvement from neuromuscular junction dysfunction, 4 patients had cranial nerve palsy, and 4 patients had non neuro-ophthalmic complications. Use of systemic corticosteroids with or without stopping the checkpoint inhibitor resulted in improvement of most patients with optic neuropathy, and variable improvement for the other ophthalmic conditions. CONCLUSION: This study describes the variable neuro-ophthalmic adverse events associated with use of immune checkpoint inhibitors and contributes a more thorough understanding of their clinical presentations and treatment outcomes. We expect this will increase awareness of these drug complications and guide specialists in the care of these patients.

A Chromosomal Deletion and New Frameshift Mutation Cause ARSACS in an African-American.

Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) is a rare, progressive, neurodegenerative disease characterized by ataxia, spasticity and polyneuropathy. First described in the French-Canadian population of Quebec in 1978, ARSACS has since been identified in multiple patients worldwide. In this clinical case report, we describe the evaluation of an 11-years-old African-American male who presented to neuromuscular clinic for assessment of a gait abnormality. He had a history of gross motor delay since early childhood, frequent falls and a below average IQ. Chromosomal microarray revealed a 1.422 megabase loss in the 13q12.12 region, which includes the SACS gene. Next Generation Sequencing then showed a novel, predicted to be pathogenic missense mutation (c.11824dup) of this gene. His clinical presentation and neurological imaging further confirmed the diagnosis of ARSACS. To our knowledge, this is the first reported case of this disease in the African-American population of the United States. This case report further highlights the growing trend of identifying genetic diseases previously restricted to single, ethnically isolated regions in many different ethnic groups worldwide.

Critical flicker fusion frequency in demyelinating and ischemic optic neuropathies.

PURPOSE: Critical flicker fusion (CFF) frequency is a well-studied test for evaluating demyelinating optic neuritis (ON). Its use in evaluating other optic neuropathies is not well established. The purpose of this study was to compare CFF in ON and non-arteritic anterior ischemic optic neuropathy (NAION). METHODS: We performed a retrospective review to compare multiple variables for eyes with ON or NAION using two-sided T tests and Chi-square tests. A multivariate linear regression was performed for the dependent variable CFF. A receiver operating characteristic (ROC) curve was used to define a CFF threshold for distinguishing these entities. RESULTS: Unaffected eyes had an average CFF value of 31.5 Hz. CFF values for ON (20.7 Hz ± 7.36) and NAION (24.3 Hz ± 9.03) were not significantly different from each other (P = 0.06). However, the CFF for ON, 18.27 Hz ± 9.29, was significantly lower than for NAION, 23.92 Hz ± 7.02, P = 0.02 when limiting the comparison to moderate and severe disease. An ROC curve demonstrates that a CFF value of ≤24 Hz is 71% sensitive for ON and that a value >24 Hz is 74% specific for excluding ON. A multivariate linear regression model demonstrated that ON contributed to approximately an 8 Hz decrease in CFF compared to NAION. Patients with a CFF of ≤24 Hz have a 2.89 odds ratio (95% CI 1.76-4.01) of having ON. CONCLUSION: CFF values in eyes with ON were significantly lower compared to eyes with NAION when evaluating moderate and severe disease. Twenty-four hertz may be a useful CFF threshold value when trying to distinguish between these two entities.

Treatment of ocular myasthenia gravis.

OPINION STATEMENT: Myasthenia gravis (MG) is an autoimmune disorder that is characterized by variable weakness and fatigability. Often, MG presents with only ocular symptoms such as ptosis and diplopia. Treatment of ocular MG is aimed at relieving the symptoms of ptosis and diplopia, as well as preventing the development of generalized MG symptoms. Immune suppression with steroids is often the main therapy. Steroid doses must be increased slowly because of a risk of precipitating myasthenic crisis. After achieving the highest target dose, steroids are then slowly tapered down to the lowest effective dose. Often, acetylcholinesterase inhibitors such as pyridostigmine and neostigmine are also employed to help control symptoms. When steroids are contraindicated, acetylcholinesterase inhibitors can be tried as the primary therapy. Steroid-sparing agents such as azathioprine and mycophenolate may also have a role in treating ocular MG. Other treatments for MG include plasmapheresis, intravenous immunoglobulin, and other immunosuppressive agents, but these are rarely required for ocular MG. Patients should also be evaluated for thymoma. Thymoma should be resected surgically. Ocular MG without thymoma is not usually treated with thymectomy. Topical agents may be useful as additional therapy for mild or moderate ptosis. Nonpharmacologic treatments include occlusive devices, prisms, eyelid supports, contact lenses, and (in long-standing, stable cases) strabismus surgery or eyelid elevation surgery.

Novel resorcinarene-based pH-triggered gelator.

Iminodiacetate resorc[4]arene is shown to produce gels that are pH-reversible. The gels formed are clear and stable to inversion. (The gels are not stable above a certain temperature, which varies with concentration.) When the pH of an iminodiacetate resorc[4]arene solution (concentration > 7.6 mM) is lowered to below 2.5, which is near one of the Ka values of the molecule, the dissolved molecules aggregate and cause gelation of water. 1H NMR showed that at the pH of gelation a change occurs in the chemical environment of the iminodiacetate group. Scanning electron microscopy showed that the gel is composed of long strands that interweave and create a molecular mesh.