Central Retinal Artery Occlusion Associated with Takayasu Arteritis.

Takayasu arteritis is a chronic inflammatory vasculitis with granulomatous panarteritis particularly impacting large vessels including the aorta and its branches, especially the subclavian arteries, with clinical manifestation dependent on the involved artery. Sequelae of the active disease vary, including stenosis, occlusions, or aneurysmal dilatations of the large vessels. The prevalence of Takayasu arteritis is higher in the Asian population and in Japan, but quite low in the United States, varying from 0.9-8.4 per million people. Ocular manifestations are rare and lead to a delay in diagnosis and appropriate treatment. Ocular manifestations include Takayasu retinopathy, anterior ischemic optic neuropathy (AION), retinal artery occlusion (RAO) and retinal vein occlusion (RVO). We present two cases in which central retinal artery occlusion (CRAO) was associated with Takayasu arteritis. CRAO is an ophthalmic emergency with an incidence of 1.9 per 100,000 person years in the United States; only 5% of cases are arteritic, which can be observed with inflammatory vasculitides secondary to the formation of immune deposits.

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.

Lumbar Puncture for Diagnosis of Idiopathic Intracranial Hypertension in Typical Patients.

BACKGROUND: Patients with typical features of pseudotumor cerebri syndrome (PTCS) must undergo lumbar puncture (LP) to demonstrate elevated opening pressure and cerebrospinal fluid (CSF) analysis to rule out alternative diagnoses. As LP may be associated with significant morbidity, this study aims to determine its necessity in diagnosing typical PTCS. METHODS: Retrospective chart review at 3 university-based neuro-ophthalmology practices included women aged 18-45 years with body mass index >25, papilledema, negative neuroimaging, and who met criteria for PTCS or probable PTCS. RESULTS: One hundred fifty-six patients were enrolled. Seven (4.5%) had clinically insignificant CSF abnormalities. No diagnoses or management changed based on LP/CSF results. CONCLUSION: LP may not be routinely required in the initial evaluation of typical patients with PTCS evaluated by experienced clinicians We caution, however, that further prospective study is required to determine potential risks and benefits of LP as a tool in the diagnosis of IIH before recommending general practice changes.

Neuro-Ophthalmic Features of Autoimmune Encephalitides.

BACKGROUND: Over the past decade, there has been a remarkable advancement in the understanding of autoimmune etiologies of encephalitis. The first identified generation of paraneoplastic encephalitis tends to occur in older populations, responds poorly to immunotherapy, and is mediated by T-cell damage with antibodies directed toward intracellular antigens. A new generation of autoimmune encephalitides has been described, which are mediated by antibodies to cell-surface proteins, tend to occur in younger individuals, are less frequently associated with malignancy, and often respond better to treatment compared to their intracellular antigen-related paraneoplastic counterparts. This review will focus on several specific antibody-mediated autoimmune encephalitides with neuro-ophthalmic pertinence. EVIDENCE ACQUISITION: Literature review and personal clinical experience. RESULTS: Several of the antibody-mediated encephalitides, specifically N-methyl-D-aspartate receptor, dipeptidyl-peptidase-like protein 6, glial fibrillary acidic protein, metabotropic glutamate receptor 1 (mGluR1), gamma-aminobutyric acid receptor, glutamic acid decarboxylase 65 (GAD65), collapsing response mediator protein 5 (CRMP5), and kelch-like protein 11 (KLHL11), contain features of neuro-ophthalmic interest. CONCLUSIONS: The novel cell-surface protein-directed autoimmune encephalitis group can present with a wide range of afferent and efferent neuro-ophthalmic manifestations. Neuro-ophthalmologists should be familiar with these antibody-associated syndromes, which are treatable and often require a high index of suspicion for diagnosis.

Disorders of Vergence Eye Movements.

PURPOSE OF REVIEW: The purpose of this review is to summarize current understanding regarding disorders of gaze with comitant ocular misalignment at distance or near and a full range of extraocular movement. Emphasis is placed on clinical features that may be used to differentiate underlying neurologic disease from the more common benign causes. The approach to the diagnostic evaluation and treatment is discussed. RECENT FINDINGS: Randomized controlled trials and Cochrane review suggest the superiority of formal office-based vision therapy in treating convergence insufficiency in children. Divergence insufficiency in older adults is a common disorder caused by involution of connective tissues in the orbit. In contrast, divergence insufficiency in children may be a harbinger of central nervous system disease, particularly intracranial tumors. Disorders of vergence are common in pediatric and aging adult populations. Benign causes are common but appropriate history and exam emphasizing ocular motility is essential to rule out more concerning diagnoses. Atypical presentations should prompt comprehensive evaluation including neuroimaging. Treatment of benign causes of vergence abnormalities should have a stepwise approach, beginning with the least invasive available intervention, though some patients may require surgery.

Preserved Visual Acuity in Anterior Ischemic Optic Neuropathy Secondary to Giant Cell (temporal) Arteritis.

OBJECTIVE: To evaluate the prevalence and clinical profile of patients with biopsy-proven arteritic anterior ischemic optic neuropathy presenting with preserved visual acuity of 20/40 or better and those with an initial poor visual acuity of 20/50 or worse through a retrospective chart review. RESULTS: Nine of 37 patients with arteritic anterior ischemic optic neuropathy presented with a preserved visual acuity of 20/40 or better in the affected eye. All patients with preserved visual acuity had initial visual field defects that spared the central field. All 37 patients immediately received high-dose corticosteroid therapy. Visual acuity worsened by > 2 lines in one of nine patients (11%) with preserved visual acuity, with a corresponding progression of visual field constriction. CONCLUSION: Although preserved visual acuity of 20/40 or better has traditionally been associated with the nonarteritic form of anterior ischemic optic neuropathy, giant cell arteritis should still be strongly considered, especially if they have giant cell arteritis systemic symptoms.

Clinical Utility of Acetylcholine Receptor Antibody Testing in Ocular Myasthenia Gravis.

IMPORTANCE: The sensitivity of acetylcholine receptor (AChR) antibody testing is thought to be lower in ocular myasthenia gravis (OMG) compared with generalized disease, although estimates in small-scale studies vary. There is little information in the literature about the implications of AChR antibody levels and progression from OMG to generalized myasthenia gravis. OBJECTIVES: To test the hypothesis that serum AChR antibody testing is more sensitive in OMG than previously reported and to examine the association between AChR antibody levels and progression from OMG to generalized myasthenia gravis. DESIGN, SETTING, AND PARTICIPANTS: A retrospective, observational cohort study was conducted of 223 patients (mean [SD] age, 59.2 [16.4] years; 139 [62.3%] male) diagnosed with OMG between July 1, 1986, and May 31, 2013, at 2 large, academic medical centers. MAIN OUTCOMES AND MEASURES: Baseline characteristics, OMG symptoms, results of AChR antibody testing, and progression time to generalized myasthenia gravis (if this occurred) were recorded for each patient. Multiple logistic regression was used to measure the association between all clinical variables and antibody result. Kaplan-Meier survival analysis was performed to examine time to generalization. RESULTS: Among the 223 participants, AChR antibody testing results were positive in 158 participants (70.9%). In an adjusted model, increased age at diagnosis (odds ratio [OR], 1.03; 95% CI, 1.01-1.04; P = .007) and progression to generalized myasthenia gravis (OR, 2.92; 95% CI, 1.18-7.26; P = .02) were significantly associated with positive antibody test results. Women were less likely to have a positive antibody test result (OR, 0.36; 95% CI, 0.19-0.68; P = .002). Patients who developed symptoms of generalized myasthenia gravis had a significantly higher mean (SD) antibody level than those who did not develop symptoms of generalized myasthenia gravis (12.7 [16.5] nmol/L vs 4.2 [7.9] nmol/L; P = .002). CONCLUSIONS AND RELEVANCE: We demonstrate a higher sensitivity of AChR antibody testing than previously reported in the largest cohort of patients with OMG available to date. Older age, male sex, and progression to generalized myasthenia gravis were significantly associated with a positive antibody test result. In addition, to our knowledge, this is the first report of an association between high AChR antibody levels and progression from OMG to generalized disease.

Prognosis of Ocular Myasthenia Gravis: Retrospective Multicenter Analysis.

PURPOSE: To calculate the rate and timing of conversion from ocular myasthenia gravis to generalized myasthenia gravis. DESIGN: Retrospective multicenter analysis. SUBJECTS: Patients included in the study were diagnosed with ocular myasthenia gravis without the presence of generalized disease at onset. METHODS: We conducted a retrospective multicenter analysis. We reviewed charts of 158 patients who met diagnostic criteria for ocular myasthenia gravis. Patients were divided into 2 subgroups: an immunosuppressant treatment group and a nonimmunosuppressant treatment group. Timing of conversion to generalized disease and duration of follow-up also was evaluated. Additional data such as clinical symptoms at presentation, laboratory test results, and chest imaging results also were recorded. MAIN OUTCOME MEASURES: Conversion rates to generalized myasthenia at 2 years, effect of immunosuppression on conversion, and timing of conversion. RESULTS: The 158-patient cohort included 76 patients who received immunosuppressant therapy; the remaining 82 patients did not. The overall conversion rate to generalized disease was 20.9%. At 2 years, generalized myasthenia developed in 8 of 76 patients in the treated group and in 15 of 82 patients in the nonimmunotherapy group (odds ratio, 0.52; 95% confidence interval, 0.20-1.32). Median time for conversion to generalized disease was 20 months in the nonimmunosuppressant group and 24 months in the immunosuppressant group. Conversion occurred after 2 years of symptom onset in 30% of patients. CONCLUSIONS: Conversion rates from ocular to generalized myasthenia gravis may be lower than previously reported both in immunosuppressed and nonimmunosuppressed patients. A subset of patients may continue to convert to generalized disease beyond 2 years from onset of symptoms, and close monitoring should be continued.

Persistent diplopia and superior oblique muscle dysfunction following dissection of the orbital periosteum in cranial base surgery.

BACKGROUND/AIMS: Persistent diplopia secondary to a fourth cranial nerve palsy is poorly documented after open cranial base surgery. METHODS: Six cases of fourth cranial nerve palsy after cranial base surgery were drawn from the Neuro-Ophthalmology and Head and Neck Surgery Clinics at the University of Michigan from 2004 to 2012. RESULTS: Six patients developed diplopia and ocular misalignment in a pattern suggestive of superior oblique palsy following dissection of the medial orbital periosteum as part of a surgical approach to the anterior cranial base. Among the four patients in whom follow-up examination was available, the misalignment improved spontaneously in three patients and was stable in the fourth patient, but did not completely resolve in any patient. CONCLUSIONS: This sparsely documented phenomenon is likely caused by dysfunction of the superior oblique muscle, possibly the result of malposition of the trochlea after spontaneous reattachment of the periosteum. Special factors such as invasive tumours, repeated surgeries of this nature, prior radiation, or chemical cementing material that adversely affects wound healing may be contributory.

Neuro-ophthalmic sarcoidosis.

PURPOSE OF REVIEW: Almost 100 years after its original description, sarcoidosis remains an enigmatic disease with unclear etiology and capricious symptomology, as well as a diagnostic challenge. This review coalesces current literature on the neuro-ophthalmic manifestations of sarcoidosis and discusses the epidemiology, etiology, clinical presentation, diagnosis, and management of this disease. RECENT FINDINGS: Recent investigations strongly identify a genetic component as well as a host of candidate antigenic triggers. Certain human leukocyte antigen polymorphisms may influence not only the susceptibility of individuals to sarcoidosis but also the course of the disease. Diagnostic advances include the finding of two additional potential biomarkers of sarcoidosis as well as the use of positron emission tomography technology in localization of disease sites for biopsy. In addition to the concomitant and alternative use of immunosuppressive agents to steroid therapy, disease remission in refractory neuro-ophthalmic sarcoidosis with tumor necrosis factor alpha inhibitors has also been reported. SUMMARY: Sarcoidosis can affect any part of the visual system; the most common neuro-ophthalmic presentation is optic neuropathy. Diagnosing the disease is problematic as the clinical presentation is nonspecific which may be associated with many other pathologies and no diagnostic finding is pathognomonic. In recent years, progress has been made in identifying new biomarkers and developing imaging techniques. Although corticosteroids remain the mainstay of therapy, many new pharmacological agents have been added to the treatment arsenal.

Optical coherence tomography: another useful tool in a neuro-ophthalmologist's armamentarium.

PURPOSE OF REVIEW: Optical coherence tomography (OCT) affords clinicians the ability to quantify the thickness of the retinal nerve fiber layer (RNFL), which is useful in managing diseases of the optic nerve. The purpose of this review is to coalesce the current literature on the use of OCT in neuro-ophthalmology to enhance its use in clinical practice. RECENT FINDINGS: OCT's advancement into spectral domain refined its ability to measure the RNFL by increasing scanner speed. Although OCT was shown to be superior to other instruments in measuring the RNFL in certain conditions, it lacks laser polarimetry's ability to detect microtubule changes. Moreover, OCT's measurements cannot be used interchangeably with other instruments' assessments of the RNFL. OCT has been studied in several neuro-ophthalmic conditions, including anterior ischemic optic neuropathy, optic neuritis/multiple sclerosis, neuromyelitis optica, pseudotumor cerebri, migraine, optic nerve head drusen, compressive optic neuropathy, and Leber's hereditary optic neuropathy. SUMMARY: OCT's wide use in evaluating the optic nerve and the visual system has revolutionized our assessment, management, research, and understanding of neuro-ophthalmic diseases.

Medical treatment options for ocular myasthenia gravis.

PURPOSE OF REVIEW: To update our current concepts of ocular myasthenia gravis medical management and to provide a short overview of upcoming treatments. RECENT FINDINGS: Cholinesterase inhibitors and corticosteroids have been the first-line treatment for ocular myasthenia gravis. Several studies on other immunosuppressants, either as a steroid-sparer, steroid adjuvant or initial monotherapy, have demonstrated significant clinical efficacy. Preventing progression to generalized myasthenia gravis is still under debate and needs to be further studied. Novel techniques that target specific components of the autoimmune cascade are forthcoming. SUMMARY: Currently, limited evidence favors the use of corticosteroids, azathioprine, and mycophenolate mofetil in ocular myasthenia gravis. There is a need for rigorous clinical trials on the efficacy and safety of these medical therapeutic options in improving ocular symptoms and decreasing the risk of developing generalized myasthenia gravis. Studies on emerging immunomodulators that dampen autoreactivity without affecting general immunity should be pursued.

Asaccadia and ataxia after repair of ascending aortic aneurysm.

Absent saccades is a rare complication of cardiovascular procedures. We present a patient who developed absent volitional saccades and reflex fast eye movements, low gain pursuit, and intact oculocephalic slow phases, dysphagia, dysarthria and progressive gait instability following repair of an ascending aortic aneurysm. Postulated pathophysiologies and prognosis for this syndrome are discussed.

Treatment of recalcitrant idiopathic orbital inflammation (chronic orbital myositis) with infliximab.

PURPOSE: To report results of treatment with a monoclonal antibody (infliximab) directed against tumor necrosis factor alpha in seven patients with chronic and difficult-to-control idiopathic orbital inflammation (orbital myositis). DESIGN: Observational case series. METHODS: Retrospective data were collected from seven patients who had idiopathic orbital inflammation and who were evaluated at three medical centers. All patients were treated with infliximab after the failure of traditional therapy, which included corticosteroids, radiotherapy, or anti-inflammatory chemotherapeutic agents. RESULTS: All seven patients had a favorable response to treatment with infliximab. One patient with Behcet disease required supplemental oral corticosteroids. Pain, swelling, and need for concomitant corticosteroids were the primary measures of treatment success. Symptoms of comorbid disease in four patients also improved (Crohn disease in two, Behcet disease in one, and psoriasis in one). There were no untoward effects of treatment after a mean follow-up of 15.7 months (range, 4 to 31 months). CONCLUSIONS: Treatment with infliximab appears to offer another therapeutic option in cases of recalcitrant or recurrent idiopathic orbital inflammation in which conventional treatment fails.

Paraneoplastic neurological autoimmunity associated with ANNA-1 autoantibody and thymoma.

Neurologic autoimmunity frequently occurs with thymoma, particularly myasthenia gravis and skeletal muscle-specific autoantibodies. Type 1 antineuronal nuclear antibody (ANNA-1/"anti-Hu"), which is recognized as an immunoglobulin G marker of small-cell lung carcinoma, has not been reported with thymoma. The authors identified four patients (three under age 40) with ANNA-1 and a paraneoplastic neurologic complication of thymoma. Retrospective testing of stored serum from 172 patients with thymoma revealed ANNA-1 in 3%. This report extends the oncologic implications of ANNA-1 seropositivity.

Resolution of papilledema after neurosurgical decompression for primary Chiari I malformation.

PURPOSE: To report a causal relationship between Chiari I malformation and its rare, but recognized manifestation of bilateral papilledema. DESIGN: Interventional case series. METHODS: Four adult female patients (mean age, 48, age range 25-59 years) with bilateral papilledema, signs and symptoms of increased intracranial pressure, and cranial magnetic resonance imaging (MRI) evidence of a Chiari I malformation ranging from 7 to 22 mm of tonsillar herniation underwent suboccipital decompression. RESULTS: In all four patients, suboccipital decompression was followed by resolution of bilateral papilledema and signs and symptoms of increased intracranial pressure. CONCLUSION: Patients with bilateral papilledema and presumed pseudotumor cerebri require a cranial MRI to determine if they have a Chiari I malformation, because patients with increased intracranial pressure and papilledema from a Chiari I malformation may benefit from suboccipital decompression.