Ocular Neuromyotonia: Clinical Features, Diagnosis, and Outcomes.

PURPOSE: The purpose of this study was to describe the clinical features, management, outcomes, and diagnostic pitfalls in a large series of patients with ocular neuromyotonia. DESIGN: Retrospective cohort. METHODS: Patients diagnosed with ocular neuromyotonia from January 1, 2004, through January 1, 2023, seen at one of the 3 Mayo Clinic sites in Rochester, MN, Scottsdale, AZ, and Jacksonville, FL, comprised the study population. We ascertained patients with ocular neuromyotonia through a search using the medical records database. Only patients with an observed episode of ocular neuromyotonia were included and the medical records were reviewed. The main outcome measures were clinical features and outcomes of patients with ocular neuromyotonia. RESULTS: Forty-two patients who were diagnosed with ocular neuromyotonia were included. The median age was 58 years (range, 16-80 years). A history of cranial radiation therapy was present in 39 patients (93%). The sixth cranial nerve was involved in 31 patients (74%). Bilateral disease was found in 2 patients (5%). The median time from onset of diplopia to diagnosis was 8 months (range, 1 month-25 years), with a high rate of initial misdiagnosis in 52%. Twenty of 42 patients (48%) were treated with oral medication, of whom 95% had significant improvement or resolution of symptoms. CONCLUSION: Prior cranial irradiation is the most common cause for ocular neuromyotonia, affecting the sixth cranial nerve most often. Although delayed and initial misdiagnosis is common, most patients show improved symptoms on medical treatment.

Characterization and Utility of Remote Interpretation of Visual Field Diagnostic Testing in an Academic Center.

BACKGROUND: The use of remote interpretation of data has risen in neuro-ophthalmology to increase efficiency and maintain social distancing due to the coronavirus disease-19 pandemic. The purpose of this study is to characterize the use and efficiency of remote interpretation of visual fields (VFs) in an academic center and to determine how often the VF interpretation was consistent with the patient's clinical history and imaging at the time of the consult. METHODS: This is a retrospective study at a single academic center that enrolled all patients receiving a remote interpretation of VF from January 1, 2012, through December 31, 2012. Data were collected regarding the referring department, indication for the VF, interpretation of the VF and comparison with any prior VFs, any associated interventions with the VF, and available follow-up VFs. The main outcome measures included 1) characterizing the use of remote VF interpretations and 2) how many remote VF interpretation results were consistent with the referring diagnosis based on the patient's clinical history and imaging. RESULTS: One hundred eighty patients received remote interpretation of VFs. The most frequent referring departments were endocrinology (79; 44%), neurology (51; 28%), and neurosurgery (43; 24%). The VF indications included parasellar lesion (107; 59%), seizure disorder (26; 14%), meningioma (19; 11%), vascular lesion (11; 6%), and others (17; 9%). There were 78 patients (43%) that had an intervention before the VF, whereas 49 (27%) were preoperative VFs. Eighty-seven (48%) of the VFs were interpreted as abnormal. Of all the 180 remote interpretation of VFs, 156 (87%) had VF interpretations that were consistent with the clinical question posed by the referring provider based on clinical history and imaging. Among the other 24 remote VF interpretations (13% of total remote VF interpretations), there was no clear interpretation because of either additional unexpected VF defects (n = 5, 21%), VF defect mismatch (n = 6, 25%), or unreliable VFs (n = 13, 54%). The median wait time for patients receiving remote VF interpretations was 1 day. CONCLUSIONS: Remote interpretation of VFs was most often requested by endocrinology, neurology, and neurosurgery and could be performed very quickly. The most common indications were parasellar lesions, and just less than half of patients receiving remote VF interpretations had a prior intervention. A majority of remote VF interpretations were able to answer the clinical question, given the patient's clinical history and imaging. Remote interpretation of VFs may thus offer referring departments a more efficient method of obtaining VF interpretations than in-office neuro-ophthalmology examinations.

Optical coherence tomography is highly sensitive in detecting prior optic neuritis.

OBJECTIVE: To explore sensitivity of optical coherence tomography (OCT) in detecting prior unilateral optic neuritis. METHODS: This is a retrospective, observational clinical study of all patients who presented from January 1, 2014, to January 6, 2017, with unilateral optic neuritis and OCT available at least 3 months after the attack. We compared OCT retinal nerve fiber layer (RNFL) and ganglion cell inner plexiform layer (GCIPL) thicknesses between affected and unaffected contralateral eyes. We excluded patients with concomitant glaucoma or other optic neuropathies. Based on analysis of normal controls, thinning was considered significant if RNFL was at least 9 µm or GCIPL was at least 6 µm less in the affected eye compared to the unaffected eye. RESULTS: Fifty-one patients (18 male and 33 female) were included in the study. RNFL and GCIPL thicknesses were significantly lower in eyes with optic neuritis compared to unaffected eyes (p < 0.001). RNFL was thinner by ≥9 µm in 73% of optic neuritis eyes compared to the unaffected eye. GCIPL was thinner by ≥6 µm in 96% of optic neuritis eyes, which was more sensitive than using RNFL (p < 0.001). When using a threshold ≤1st percentile of age-matched controls, sensitivities were 37% for RNFL and 76% for GCIPL, each of which was lower than those calculated using the intereye difference as the threshold (p < 0.01). CONCLUSIONS: OCT, especially with GCIPL analysis, is a highly sensitive modality in detecting prior optic neuritis, which is made more robust by using intereye differences to approximate change. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that OCT accurately identifies patients with prior unilateral optic neuritis.

A Population-Based, Case-Control Evaluation of the Association Between Hormonal Contraceptives and Idiopathic Intracranial Hypertension.

PURPOSE: To determine if the use of oral contraceptive pills (OCP) and other hormonal contraceptives are associated with a higher incidence of idiopathic intracranial hypertension (IIH). DESIGN: Retrospective, population-based, case-control study. METHODS: Setting: Female IIH patients evaluated between January 1, 1990, and December 31, 2016 were identified using the Rochester Epidemiology Project (REP), a record-linkage system of medical records for all patient-physician encounters among Olmsted County, Minnesota, residents. STUDY POPULATION: Fifty-three female residents of Olmsted County diagnosed with IIH between 15 and 45 years of age. The use of OCPs and other hormonal contraceptives was compared to controls matched for age, sex, and body mass index. Interventions/Exposures: Hormonal contraceptives. MAIN OUTCOME MEASURE: Odds of developing IIH. RESULTS: Of the 53 women diagnosed with IIH between 15 and 45 years of age, 11 (20.8%) had used hormonal contraceptives within ≤30 days of the date of IIH diagnosis, in contrast to 30 (31.3%) among the control patients. The odds ratio of hormonal contraceptive use and IIH was 0.55 (95% conficence interval [CI]: 0.24-1.23, P = .146). The odds ratio of OCP use was 0.52 (95% CI: 0.20-1.34, P = .174). CONCLUSIONS: OCP and other hormonal contraceptives were not significantly associated with a higher incidence of IIH, arguing against the need for women with IIH to discontinue their use.

Myelin Oligodendrocyte Glycoprotein Antibody-Positive Optic Neuritis: Clinical Characteristics, Radiologic Clues, and Outcome.

PURPOSE: To characterize the clinical phenotype of myelin oligodendrocyte glycoprotein antibody (MOG-IgG) optic neuritis. DESIGN: Observational case series. METHODS: Setting: Multicenter. Patient/Study Population: Subjects meeting inclusion criteria: (1) history of optic neuritis; (2) seropositivity (MOG-IgG binding index > 2.5); 87 MOG-IgG-seropositive patients with optic neuritis were included (Mayo Clinic, 76; other medical centers, 11). MOG-IgG was detected using full-length MOG-transfected live HEK293 cells in a clinically validated flow cytometry assay. MAIN OUTCOME MEASURES: Clinical and radiologic characteristics and visual outcomes. RESULTS: Fifty-seven percent were female and median age at onset was 31 (range 2-79) years. Median number of optic neuritis attacks was 3 (range 1-8), median follow-up 2.9 years (range 0.5-24 years), and annualized relapse rate 0.8. Average visual acuity (VA) at nadir of worst attack was count fingers. Average final VA was 20/30; for 5 patients (6%) it was ≤20/200 in either eye. Optic disc edema and pain each occurred in 86% of patients. Magnetic resonance imaging showed perineural enhancement in 50% and longitudinally extensive involvement in 80%. Twenty-six patients (30%) had recurrent optic neuritis without other neurologic symptoms, 10 (12%) had single optic neuritis, 14 (16%) had chronic relapsing inflammatory optic neuropathy, and 36 (41%) had optic neuritis with other neurologic symptoms (most neuromyelitis optica spectrum disorder-like phenotype or acute disseminated encephalomyelitis). Only 1 patient was diagnosed with MS (MOG-IgG-binding index 2.8; normal range ≤ 2.5). Persistent MOG-IgG seropositivity occurred in 61 of 62 (98%). A total of 61% received long-term immunosuppressant therapy. CONCLUSIONS: Manifestations of MOG-IgG-positive optic neuritis are diverse. Despite recurrent attacks with severe vision loss, the majority of patients have significant recovery and retain functional vision long-term.

Comparison of Ocular Ultrasonography and Magnetic Resonance Imaging for Detection of Increased Intracranial Pressure.

BACKGROUND/AIMS: To evaluate and compare the performance of ocular ultrasonography (US) and magnetic resonance imaging (MRI) for detecting increased intracranial pressure (ICP) in patients with idiopathic intracranial hypertension (IIH). METHODS: Twenty-two patients with papilledema from IIH and 22 with pseudopapilledema were prospectively recruited based on funduscopic and clinical findings. Measurements of optic nerve sheath diameters (ONSDs) 3 mm behind the inner sclera were performed on B-scan US and axial T2-weighted MRI examinations. Pituitary-to-sella height ratio (pit/sella) was also calculated from sagittal T1-weighted MRI images. Lumbar puncture was performed in all patients with IIH and in five patients with pseudopapilledema. RESULTS: Average US and MRI ONSD were 4.4 (SD ± 0.7) and 5.2 ± 1.4 mm for the pseudopapilledema group and 5.2 ± 0.6 and 7.2 ± 1.6 mm for the papilledema group (p < 0.001). Average MRI pit/sella ratio was 0.7 ± 0.3 for the pseudopapilledema group and 0.3 ± 0.2 for the papilledema group (p < 0.001). Based on receiver-operator curve analysis, the optimal thresholds for detecting papilledema are US ONSD > 4.8 mm, MRI ONSD > 6.0 mm, and MRI pit/sella < 0.5. Combining a dilated US ONSD or MRI ONSD with a below-threshold MRI pit/sella ratio yielded a sensitivity of 73% and specificity of 96% for detecting IIH. Adding the US ONSD to the MRI ONSD and pit/sella ratio only increased the sensitivity by 5% and did not change specificity. CONCLUSION: US and MRI provide measurements of ONSD that are well-correlated and sensitive markers for increased ICP. The combination of the ONSD and the pit/sella ratio can increase specificity for the diagnosis of IIH.

Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein Autoantibody Status Predict Outcome of Recurrent Optic Neuritis.

PURPOSE: To determine the aquaporin-4 and myelin oligodendrocyte glycoprotein (MOG) immunoglobulin G (IgG) serostatus and visual outcomes in patients with recurrent optic neuritis (rON) initially seeking treatment. DESIGN: Cross-sectional cohort study. PARTICIPANTS: The study identified patients by searching the Mayo Clinic computerized central diagnostic index (January 2000-March 2017). The 246 eligible patients fulfilled the following criteria: (1) initially seeking treatment for at least 2 consecutive episodes of optic neuritis (ON) and (2) serum available for testing. METHODS: Serum was tested for aquaporin-4 IgG and MOG IgG1 using an in-house validated flow cytometric assay using live HEK293 cells transfected with M1 aquaporin-4 or full-length MOG. MAIN OUTCOMES MEASURES: Aquaporin-4 IgG and MOG IgG1 serostatus, clinical characteristics, and visual outcomes. RESULTS: Among 246 patients with rON at presentation, glial autoantibodies were detected in 32% (aquaporin-4 IgG, 19%; MOG IgG1, 13%); 186 patients had rON only and 60 patients had rON with subsequent additional inflammatory demyelinating attacks (rON-plus group). The rON-only cohort comprised the following: double seronegative (idiopathic), 110 patients (59%); MOG IgG1 positive, 27 patients (15%; 4 with chronic relapsing inflammatory optic neuropathy); multiple sclerosis (MS), 25 patients (13%); and aquaporin-4 IgG positive, 24 patients (13%). The rON-plus cohort comprised the following: aquaporin-4 IgG positive, 23 patients (38%); MS, 22 patients (37%); double seronegative, 11 patients (18%); and MOG IgG1 positive, 4 patients (7%). The annualized relapse rate for the rON-only group was 1.2 for MOG IgG1-positive patients, 0.7 for double-seronegative patients, 0.6 for aquaporin-4 IgG-positive patients, and 0.4 for MS patients (P = 0.005). The median visual acuity (VA) of patients with the worst rON-only attack at nadir were hand movements in aquaporin-4 IgG-positive patients, between counting fingers and hand movements in MOG IgG1-positive patients, 20/800 in idiopathic patients, and 20/100 in MS patients (P = 0.02). The median VA at last follow-up for affected eyes of the rON-only cohort were counting fingers for aquaporin-4 IgG-positive patients, 20/40 for idiopathic patients, 20/25 for MS patients and MOG IgG1-positive patients (P = 0.006). At 5 years after ON onset, 59% of aquaporin-4 IgG-positive patients, 22% of idiopathic patients, 12% of MOG IgG1-positive patients, and 8% of MS patients were estimated to have severe visual loss. CONCLUSIONS: Glial autoantibodies (MOG IgG1 or aquaporin-4 IgG) are found in one third of all patients with rON. Aquaporin-4 IgG seropositivity predicts a worse visual outcome than MOG IgG1 seropositivity, double seronegativity, or MS diagnosis. Myelin oligodendrocyte glycoprotein IgG1 is associated with a greater relapse rate but better visual outcomes.

Papilloedema and Autoimmune Retinopathy from Systemic Lupus Erythematosus.

A 33-year-old female presented with bilateral papilloedema and constricted visual fields from autoimmune retinopathy. She then developed a painful peripheral neuropathy that led to further work-up and the diagnosis of systemic lupus erythematosus. Papilloedema and autoimmune retinopathy from systemic lupus erythematosus is a unique presentation.

Prevalence of Myelin Oligodendrocyte Glycoprotein and Aquaporin-4-IgG in Patients in the Optic Neuritis Treatment Trial.

Importance: Autoantibodies to aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) are recently established biomarkers of autoimmune optic neuritis whose frequency and accompanying phenotype, especially for MOG-IgG, are still being characterized. The Optic Neuritis Treatment Trial (ONTT) was a well-known randomized clinical trial in optic neuritis; therefore, knowledge of the serostatus and accompanying phenotype of these patients would be useful to determine the frequency of these antibodies in patients presenting with typical monocular optic neuritis and their outcomes. Objectives: To determine the AQP4-IgG and MOG-IgG serostatus of patients within the ONTT and describe the clinical features of seropositive patients. Design, Setting, and Participants: In this follow-up study of the randomized clinical trial, ONTT, conducted between July 1, 1988, and June 30, 1991, analysis of serum for AQP4-IgG and MOG-IgG was performed from January 1 to April 30, 2017. A total of 177 patients from the ONTT with acute optic neuritis and serum available for analysis were enrolled from 13 academic referral centers. Interventions: Analysis of serum for AQP4-IgG and MOG-IgG was performed at Mayo Clinic Neuroimmunology Laboratory in 2017 with a flow cytometry, live cell, AQP4- and MOG-transfected cell-based assay. Main Outcomes and Measures: Aquaporin-4-IgG and MOG-IgG serostatus. Results: Of the 177 patients in the study (135 women and 42 men; mean [SD] age, 32.8 [6.9] years), 3 were positive for MOG-IgG (1.7%) and none were positive for AQP4-IgG. All 3 patients positive for MOG-IgG had disc edema at presentation. Two patients later had a single episode of recurrent optic neuritis. All 3 patients had complete recovery of visual acuity, and none were corticosteroid dependent, although peripheral visual field loss persisted in 1 patient. None of the 3 patients positive for MOG-IgG had demyelinating lesions on magnetic resonance imaging scans, and none had developed multiple sclerosis at the 15-year follow-up. Conclusions and Relevance: Frequency of MOG-IgG was rare in the ONTT, and AQP4-IgG was not found in patients in the ONTT. Characteristics of patients positive for MOG-IgG in the ONTT support the previously described phenotype of MOG-IgG optic neuritis. Myelin oligodendrocyte glycoprotein-related disease appears to be a different entity than multiple sclerosis. Overall, AQP4-IgG and MOG-IgG may be less common in isolated optic neuritis than previously reported.

Retinal Arterio-Arterial Collaterals in Susac Syndrome.

BACKGROUND: The ophthalmic findings of Susac syndrome (SS) consist of visual field defects related to branch retinal artery occlusion (BRAO), and fluorescein angiography (FA) reveals a unique staining pattern. To date, retinal arterial collateral development has been described only in a single patient. Given that the immunopathological process in SS induces retinal ischemia, it is conceivable that abnormal blood vessel development may occur in affected individuals. METHODS: This is a retrospective observational study. The medical records including fundus photography and FA of all patients with SS were reviewed, and those with any type of retinal arterial collateral were identified. RESULTS: A total of 11 patients were identified with retinal collaterals. Five were men. Age ranged from 20 to 50 years. Ten patients had arterio-arterial (A-A) collaterals and 1 had arterio-venous (A-V) collaterals, and all had collaterals remote from the optic disc. No collaterals were present at onset of illness and the first developed at 9 months. CONCLUSIONS: The literature reveals scant evidence for the association between BRAO and retinal arterial collaterals. Our findings indicate that retinal arterial collaterals in SS are usually A-A and not A-V and may be more common in this disorder than previously believed. Collaterals do not develop early in the disease, and there may be a predilection toward development in men. The chronic inflammatory state of SS may be the stimulus for the development of these arterial collaterals.

Optic Disc Edema in Glial Fibrillary Acidic Protein Autoantibody-Positive Meningoencephalitis.

BACKGROUND: Glial fibrillary acidic protein (GFAP) autoantibody-positive meningoencephalitis is a newly described entity characterized by a corticosteroid-responsive meningoencephalomyelitis. Some patients with GFAP autoantibody-positive meningoencephalitis have been found to have optic disc edema, which has previously not been well characterized. METHODS: We performed a retrospective, observational case series of Mayo Clinic patients found to have GFAP-IgG and optic disc edema from January 1, 2000, to December 31, 2016. We identified 40 patients with GFAP-IgG seropositivity by tissue-based immunofluorescence and cell-based assay. Patients were screened for the following inclusion criteria: 1) serum, cerebrospinal fluid, or both that yielded a characteristic astrocytic pattern of mouse tissue immunostaining with confirmation of IgG reactive with specific GFAPα isoform by cell-based assay; 2) meningoencephalitis or encephalitis; and 3) optic disc edema. We excluded those with coexisting aquaporin-4-IgG or insufficient clinical information. RESULTS: Ten patients had optic disc edema and met inclusion criteria. The median age was 39.5 years and 60% were men. Visual acuity was unaffected and disc edema was bilateral in all cases. Mild vitreous cell was noted in 3 patients. The optic disc edema resolved with corticosteroid treatment but resulted in mild optic atrophy in 2 patients. The median lumbar puncture opening pressure was 144 mm H2O (range, 84-298 mm H2O). Brain MRI revealed radial perivascular enhancement in all except 1 patient. Fluorescein angiography was available for 1 patient with optic disc edema, which showed leakage from the venules. CONCLUSIONS: Patients with GFAP autoantibody-positive meningoencephalitis can have optic disc edema that can mimic papilledema. The cause of the optic disc edema remains uncertain, but most patients did not have raised intracranial pressure.

Optical Coherence Angiographic Demonstration of Retinal Changes From Chronic Optic Neuropathies.

Glaucoma causes a decrease in peripapillary perfused capillary density on optical coherence tomography (OCT) angiography. However, other chronic optic neuropathies have not been explored with OCT angiography to see if these changes were specific to glaucoma. The authors evaluated OCT angiography in 10 patients who suffered various kinds of chronic optic neuropathies, including optic neuritis and ischaemic optic neuropathy, and found that all optic neuropathies showed a decrease in peripapillary vessel density on OCT angiography, regardless of the aetiology of the optic neuropathy. The peripapillary vessel loss on OCT angiography correlated well with the areas of retinal nerve fibre layer thinning seen on OCT.

Re-evaluating the Incidence of Idiopathic Intracranial Hypertension in an Era of Increasing Obesity.

PURPOSE: To re-evaluate the population-based incidence of idiopathic intracranial hypertension (IIH) and to determine if it mirrors the rise in obesity. DESIGN: Retrospective, population-based cohort. PARTICIPANTS: All residents of Olmsted County, Minnesota, diagnosed with IIH between January 1, 1990, and December 31, 2014. METHODS: All cases of IIH were identified using the Rochester Epidemiology Project, which is a record-linkage system of medical records for all patient-physician encounters among Olmsted County, Minnesota, residents. All medical records were reviewed to confirm a diagnosis of IIH. The incidence rates of IIH were compared against the incidence of obesity in Minnesota over the same period. MAIN OUTCOME MEASURES: Incidence of IIH, lumbar puncture opening pressures, and body mass index. RESULTS: There were 63 new cases of IIH, yielding an overall age- and gender-adjusted annual incidence of 1.8 per 100 000 (95% confidence interval, 1.3-2.2) between 1990 and 2014. It increased from 1.0 per 100 000 (1990-2001) to 2.4 per 100 000 (2002-2014; P = 0.007). The incidence of IIH was 3.3 per 100 000 in women and 0.3 per 100 000 in men (P ≤ 0.001). In obese women 15 to 44 years of age, the incidence was 22.0 per 100 000 compared with 6.8 per 100 000 among all women in the same age group. A strong correlation was observed between IIH incidence rates and obesity rates in Minnesota (R2 = 0.70, P = 0.008). CONCLUSIONS: The incidence of IIH has increased since 1990, which is highly correlated with the rise in obesity during the same period.

Incidence and Etiologies of Acquired Third Nerve Palsy Using a Population-Based Method.

IMPORTANCE: Among cranial nerve palsies, a third nerve palsy is important because a subset is caused by life-threatening aneurysms. However, there is significant disagreement regarding its incidence and the reported etiologies. OBJECTIVE: To determine the incidence and etiologies of acquired third nerve palsy using a population-based method. DESIGN, SETTING, AND PARTICIPANTS: All newly diagnosed cases of acquired third nerve palsy from January 1, 1978, through December 31, 2014, in Olmsted County, Minnesota, were identified using the Rochester Epidemiology Project, a record-linkage system of medical records for all patient-physician encounters among Olmsted County residents. All medical records were reviewed to confirm a diagnosis of acquired third nerve palsy and determine the etiologies, presenting signs, and symptoms. Incidence rates were adjusted to the age and sex distribution of the 2010 US white population. MAIN OUTCOMES AND MEASURES: Incidence and etiologies of acquired third nerve palsies. The secondary outcome was incidence of pupil involvement in acquired third nerve palsies. RESULTS: We identified 145 newly diagnosed cases of acquired third nerve palsy in Olmsted County, Minnesota, over the 37-year period. The age- and sex-adjusted annual incidence of acquired third nerve palsy was 4.0 per 100 000 (95% CI, 3.3-4.7 per 100 000). The annual incidence in patients older than 60 was greater than patients younger than 60 (12.5 vs 1.7 per 100 000; difference, 10.8 per 100 000; 95% CI, 4.7-16.9; P < .001). The most common causes of acquired third nerve palsy were presumed microvascular (42%), trauma (12%), compression from neoplasm (11%), postneurosurgery (10%), and compression from aneurysm (6%). Ten patients (17%) with microvascular third nerve palsies had pupil involvement, while pupil involvement was seen in 16 patients (64%) with compressive third nerve palsies. CONCLUSIONS AND RELEVANCE: This population-based cohort demonstrates a higher incidence of presumed microvascular third nerve palsies and a lower incidence of aneurysmal compression than previously reported in non-population-based studies. While compressive lesions had a higher likelihood of pupil involvement, pupil involvement did not exclude microvascular third nerve palsy and lack of pupil involvement did not rule out compressive third nerve palsy.