Neuro-ophthalmic Presentation Research Articles

Update on Neuro-ophthalmic Manifestations of Immune Checkpoint Inhibitors.

Immune checkpoint inhibitor (ICI) use has been on the rise for treatment of many different malignancies. Subsequently, more has been learned about immune-related adverse events (irAEs) that occur up to 12months after treatment. This review summarizes the latest findings and management of neuro-ophthalmic associated irAEs. irAEs can affect the afferent and efferent neuro-ophthalmic pathways, thereby targeting central and peripheral nervous systems. As more cases are being reported, it is becoming apparent that neuro-ophthalmic irAEs often present with atypical features when compared to their spontaneous autoimmune counterparts. These neuro-ophthalmic presentations can also be signs of a more extensive inflammatory process that spans other organ systems, such as myopathies, endocrinopathies, and paraneoplastic syndromes. Awareness of neuro-ophthalmic irAEs and their atypical presentations can lead to early detection, termination of ICI treatment, and immunosuppressant therapy initiation.

Simultaneous Neuro-Ophthalmic Presentation and Progression of Idiopathic Intracranial Hypertension and Multiple Sclerosis.

Simultaneous Neuro-Ophthalmic Presentation and Progression of Idiopathic Intracranial Hypertension and Multiple Sclerosis.

Protean Neuroophthalmic Presentations of Common Childhood Malignancies—A Report of Two Cases

AbstractCommon pediatric malignancies often surprise clinicians with unusual presentations. In this narrative, we report two patients with common childhood cancer having unique neuroophthalmic characteristics. In the first case, we have a child with a common childhood solid tumor presenting with blindness without proptosis, while the second case is of a child with a common hematological malignancy presenting with unilateral proptosis without visual impairment. The report highlights that common childhood cancers may present with neuroophthalmic symptoms on rare occasions, creating a diagnostic conundrum.

Effect of vitamin A on recovery from the acute phase of multiple sclerosis-related optic neuritis, double-blind, randomized, placebo-controlled trial.

Optic neuritis (ON) is one of the main neuro-ophthalmic presentations of multiple sclerosis (MS), and it causes optic nerve atrophy and axonal loss. However, so far, there is no effective treatment to improve long-term outcomes. In a double-blind placebo-controlled randomized clinical trial, 50 patients with MS-related ON were allocated into two arms (24 in the control group and 26 in the intervention group) receiving either 25000IU retinyl palmitate or an identical placebo for six months. Visual evoked potential (VEP), visual acuity, and the retinal nerve fiber layer (RNFL) thickness were evaluated and compared before and after the treatment. RNFL thickness reduction in the affected eyes at sixth month compared to the baseline were 14.81 and 19.46 μm, in the intervention and control groups, respectively (P=0.017). However, VitA therapy did not affect visual acuity and VEP. Vitamin A supplementation in the patients with acute ON in MS could lessen optic nerve axonal loss.

Isolated Eight and Half Syndrome, a Rare Neuro-ophthalmic Presentation: A Case Report

Eight and half syndrome is one of the rare neurological disorders, which is usually overlooked in our clinical practice. Here I report 58 years-old hypertensive Indian gentleman presented with horizontal gaze palsy and facial weakness.

Neuro-Ophthalmic Presentations of Common Carotid Artery Occlusion: A Case Series.

Neuro-Ophthalmic Presentations of Common Carotid Artery Occlusion: A Case Series.

Neuro-Ophthalmic Manifestations of Sarcoidosis.

Sarcoidosis is an idiopathic, multisystem, inflammatory disease that has central nervous system involvement in 5%-15% of cases. The presentation of neurosarcoidosis is highly variable, and the MRI findings often mimic the appearance of other central nervous system diseases. Therefore, the diagnosis can be challenging. About one-third of neurosarcoidosis cases have neuro-ophthalmic manifestations and, thus, may be evaluated by a neuro-ophthalmologist early in the disease course. We performed a retrospective review of 22 cases of biopsy-proven sarcoidosis with neuro-ophthalmic manifestations, seen at the Wilmer Eye Institute from January 2013 to September 2019, in which we described the demographic information, clinical presentations, neuroimaging findings, and diagnostic evaluations. Twenty-two patients were included. Fifteen patients identified as black and 7 as white. Fifteen were women, and 7 men. Mean age at sarcoidosis diagnosis was 45.9 years (range 26-66). Neuro-ophthalmic findings included optic neuropathy in 11 (50%); proptosis/orbital inflammation in 5 (23%); abducens palsy in 5 (23%); trochlear palsy, trigeminal distribution numbness, and bitemporal hemianopia in 2 each (9%); and oculomotor palsy, facial palsy, optic perineuritis, dorsal midbrain syndrome, central vestibular nystagmus, and papilledema in 1 each (5%). Eight (36%) had a pre-existing diagnosis of sarcoidosis; however, in 14 (64%), the neuro-ophthalmic presentation led to the sarcoidosis diagnosis. Patients with a pre-existing sarcoidosis diagnosis were younger than those without this diagnosis (38.5 vs 50.1 years, P = 0.035). Brain MRI was abnormal in all but 1 case (95%). In patients without a pre-existing sarcoidosis diagnosis, all 7 tested for angiotensin converting enzyme (ACE) had normal values, and 75% of the 12 who had computed tomography (CT) chest had findings suggestive of sarcoidosis (86% of black patients vs 50% of white patients). Patients with neurosarcoidosis may present initially with a neuro-ophthalmic manifestation, and this presentation may be more common in older patients. MRI usually is abnormal, although findings may be nonspecific. Serum testing for ACE is not helpful. Normal CT chest does not rule out underlying sarcoidosis, particularly in white patients.

Neuro-Ophthalmic Manifestations of Acute Leukemia.

Ophthalmic involvement in acute leukemia is common, with 36% of patients having ophthalmic involvement at the time of diagnosis. However, neuro-ophthalmic involvement is relatively rare. We present a characterization of neuro-ophthalmic findings in patients with acute leukemia and discuss the implications of these findings on patient management and prognosis. We performed a retrospective review of cases of acute leukemia with central nervous system (CNS) involvement and neuro-ophthalmic manifestations that were evaluated at the Wilmer Eye Institute between January 2013 and September 2019. Data collected included demographic information, leukemia details, results of diagnostic testing, and features of associated neuro-ophthalmic manifestations. Twelve patients with mean age 42 years (range 9-65, median 39) were included. Seven (58%) patients were men and 5 (42%) women. Eight (67%) were diagnosed with acute myeloid leukemia and 4 (33%) with acute lymphoid leukemia. Neuro-ophthalmic findings included 4 patients with isolated sixth nerve palsies, 2 with multiple cranial nerve palsies, 2 with orbital lesions with proptosis, 4 with optic disc swelling, and 1 with isolated fourth nerve palsy. Five (42%) neuro-ophthalmic presentations were associated with known CNS disease, 3 (25%) were associated with active disease but heralded the discovery of CNS involvement, 3 (25%) were the presenting features of relapse, and 1 (8%) led to the original leukemia diagnosis. Neuroimaging showed 4 with leptomeningeal enhancement, 4 with cranial nerve enhancement/thickening, 3 with optic nerve/sheath enhancement, 1 with lytic lesion of bone, 1 with soft tissue mass, and 1 with cytotoxic brain edema. One case had normal neuroimaging. Overall, patients had a poor prognosis, with 7 patients dying from leukemia or its complications and only 1 achieving a sustained remission. In 58% of the cases in our series, the discovery of neuro-ophthalmic leukemic involvement directly led to a change in leukemia treatment. Neuro-ophthalmic manifestations of leukemia may occur as presenting features of diagnosis, relapse, or CNS involvement, and portend a poor prognosis. Detection of neuro-ophthalmic involvement often triggers a prompt change in management. Therefore, familiarity with potential neuro-ophthalmic presentations of acute leukemia may avoid delayed diagnosis, and resultant inadequate treatment, of primary disease, relapse, or CNS involvement.

Neuro-Ophthalmic Manifestations of Intracranial Malignancies.

To describe the various neuro-ophthalmic presentations, key exam features, and clinical findings associated with 5 common primary and secondary intracranial malignancies. Retrospective PubMed search and review of published case reports, case series, observational studies, book chapters, and review articles examining the neuro-ophthalmic features of intracranial malignancies including primary glial neoplasms (e.g., glioblastoma multiforme), primary and secondary lymphoma, intracranial metastases, carcinomatous/lymphomatous meningitis, and intracranial germ cell tumors. The search strategy used to perform the retrospective review included the aforementioned tumor type (e.g., glioblastoma multiforme) and the following terms and Boolean operators: AND ("visual loss" OR "papilledema" OR "diplopia" OR "ophthalmoplegia" or "neuro-ophthalmology" OR "proptosis"). The rate of growth and the location of an intracranial tumor are essential factors in determining the neuro-ophthalmic presentation of certain intracranial malignancies. Primary malignant brain glial neoplasms commonly present with visual afferent complaints (e.g., unilateral or bilateral visual acuity or visual field defects, bitemporal or homonymous hemianopsia), pupil abnormalities (relative afferent pupillary defect), and optic atrophy or papilledema. Primary intraocular lymphoma (with or without central nervous system lymphoma) typically presents as a painless bilateral vitritis. Secondary intracranial malignancies have variable afferent and efferent visual pathway presentations. Carcinomatous/lymphomatous meningitis is associated with diplopia (e.g., multiple ocular motor cranial neuropathies with or without vision loss from papilledema or compressive/infiltrative optic neuropathy). Intracranial germ cell tumors can present with a chiasmal syndrome or dorsal midbrain syndrome. Intracranial malignancies can present with neuro-ophthalmic symptoms or signs depending on topographical localization. Specific neuro-ophthalmic presentations are associated with different malignant intracranial tumors. Clinicians should be aware of the common malignant intracranial tumors and their associated clinical presentations in neuro-ophthalmology.

Should Tocilizumab Be Used Routinely in New Patients With a Diagnosis of Giant Cell Arteritis?

Should Tocilizumab Be Used Routinely in New Patients With a Diagnosis of Giant Cell Arteritis?

Isolated unilateral sixth nerve palsy in a patient with nasopharyngeal carcinoma

Objective: To describe an isolated unilateral sixth nerve palsy, as a rare neuro-ophthalmic presentation of nasopharyngeal carcinoma. Methods: We report a 54-year-old female, known case of nasopharyngeal carcinoma who was treated with chemo-radiotherapy, and presented with isolated right sixth nerve palsy. Magnetic resonance imaging (MRI) indicated extension of tumor to intracranial fossa with clival involvement. Results: The patient was referred to an otolaryngologist for further evaluation and necessary intervention due to invasion of the cancer to intracranial fossa with involvement of right abducens nerve. Conclusions: Although, isolated sixth nerve palsies in adults over the age of 50 are usually ischemic; but in enduring cases, neoplastic processes should be considered.

Vertebrobasilar ischemia (VBI) related neuro-ophthalmic syndromes after routine activities involving hyperextension or rotation of the neck (hairdresser syndrome).

Vertebrobasilar insufficiency (VBI) after rotation or hyperextension of the neck during otherwise routine activities is uncommon "hairdresser syndrome" (HDS). We report three such cases presenting with neuro-ophthalmic complaints (Horner syndrome, ophthalmoplegia, and transient vision loss). A retrospective review was performed of the electronic health records of three patients seen in the neuro-ophthalmology clinic of Houston Methodist Hospital with acute neuro-ophthalmological signs after neck hyperextension. A literature review was also performed. While various ischemic signs of VBI have been previously documented, to our knowledge, these are the first cases in the English ophthalmic literature to describe the presenting neuro-ophthalmologic signs of HDS. Clinicians should consider the possibility of neck hyperextension as a potential mechanism and precipitating event for acute neuro-ophthalmic presentations of VBI. Patients with a history of occupational (e.g., carpenter), recreational (e.g., bow hunter), or cosmetic (hairdresser) neck hyperextension (i.e., possible HDS) should undergo structural and vascular neuroimaging of both the head and neck (e.g., CT/CTA or MRI/MRA) to look for evidence of posterior fossa ischemia and/or vertebrobasilar lesion (e.g., occlusion, dissection, FMD, and pseudoaneurysm).

The Neuro-ophthalmic Presentation of Intracranial Aneurysms

The Neuro-ophthalmic Presentation of Intracranial Aneurysms

Unique neuro-ophthalmic presentation of gun pellet injury.

We describe a unique case of orbital gunshot injury with isolated intraorbital pellets lodged symmetrically in the two apices, causing identical clinical presentation, and absence of any associated globe or cerebral injury. He developed bilateral complete third nerve palsy with bilateral traumatic optic neuropathy. The optic nerve strut prevented the pellets from going into the brain on both the sides.

Neuro-ophthalmic presentations and treatment of Cryptococcal meningitis-related increased intracranial pressure

ObjectiveTo illustrate three different ophthalmic presentations of cryptococcal meningitis (CM). IntroductionCM is the most common manifestation of extra-pulmonary cryptococcosis. Intracranial hypertension occurs in up to 75% of patients with CM and is associated with increased mortality. CM can present to the ophthalmologist as vision loss, papilledema, abducens palsy, and/or other cranial neuropathies. Participants and MethodsWe report three cases, two C. neoformans and one C. gattii, highlighting the various CM presentations. The first was a woman immunosuppressed following kidney transplantation in whom idiopathic intracranial hypertension (IIH) was initially suspected. The second was a man immunocompromised by previously undiagnosed HIV/AIDS who presented with signs and symptoms of increased intracranial pressure. The third case is an immunocompetent man with bilateral disc edema and an incomplete macular star diagnosed with presumed neuroretinitis. Further evaluation revealed positive CSF cryptococcal antigen with culture positive for C. gattii. ConclusionsOphthalmologists should be aware that cryptococcosis can mimic more benign etiologies including IIH and neuroretinitis. Additionally, C. gattii, an emerging organism, can infect immunocompetent patients. In contrast to the typical treatment of increased ICP, serial lumbar punctures are recommended while acetazolamide and surgical CSF shunting may be harmful.

Mitochondrial dysfunction affecting visual pathways

Mitochondrial dysfunction leads to cellular energetic impairment, which may affect the visual pathways, from the retina to retrochiasmal structures. The most common mitochondrial optic neuropathies include Leber's hereditary optic neuropathy and autosomal dominant optic atrophy, but the optic nerve can be affected in other syndromic conditions, such as Wolfram syndrome and Friedreich's ataxia. These disorders may result from mutations in either the mitochondrial DNA or in the nuclear genes encoding mitochondrial proteins. Despite the inconstant genotype-phenotype correlations, a clinical classification of mitochondrial disorders may be made on the basis of distinct neuro-ophthalmic presentations such as optic neuropathy, pigmentary retinopathy and retrochiasmal visual loss. Although no curative treatments are available at present, recent advances throw new light on the pathophysiology of mitochondrial disorders. Current research raises hopes for novel treatment of hereditary optic neuropathies, particularly through the use of new drugs and mitochondrial gene therapy.

The Urgency of Neuroimaging Among UK Neuro-Ophthalmologists: Consensus and Disagreement

The timing of imaging in neuro-ophthalmology is critical. There are few published studies, however, that address the question of how urgently to request imaging for neuro-ophthalmic clinical scenarios. We therefore conducted a national survey of expert opinion on the urgency of neuroimaging in neuro-ophthalmology. We devised a list of 40 clinical scenarios, reflecting a wide range of neuro-ophthalmic presentations. For each scenario, respondents were asked to state how urgently they would obtain neuroimaging in day-to-day NHS (National Health Service) practice. There were five response options: “Emergency” (i.e., within 1 d), “Urgent” (i.e., within 1 week), “Semi-urgent” (i.e., within 1 month), “Observation” (only if not resolving after a period of observation [greater than 1 month]), and “Not normally scanned unless new features appear.” Respondents were recruited by e-mailing individuals who were on the UKNOSIG (UK Neuro-Ophthalmology Special Interest Group) mailing list. All were Consultant Ophthalmologists or Neurologists specialising in neuro-ophthalmology. Consensus was set at an a priori level of 80% agreement. Only 17 out of 40 scenarios met the criterion for consensus. Nine of these were for emergency/urgent imaging, three were for not imaging, and five were for semi-urgent imaging. For the remaining 23 scenarios, consensus was not reached. Unanimity (100% agreement) was not reached for any scenario. Agreement between neuro-ophthalmologists on the urgency of neuroimaging is patchy, with consensus for some clinical scenarios and disagreement for many. There is a need for a prospective study of neuroimaging in neuro-ophthalmology to determine whether timing of imaging influences outcomes.

Neuro-ophthalmic sarcoidosis

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 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. 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.

Neuro-ophthalmologic Manifestations of Primary Headache Disorders

Headaches are the most common disorders of the central nervous system affecting 46% of the adult population worldwide. Headaches may be lifelong illnesses, often associated with substantial disability for the individual and the population as a whole. The International Classification of Headache Disorders (ICHD-II) codifies headache disorders into fourteen categories, predominantly primary headaches and secondary headache disorders. Primary headache disorders, mainly migraine and trigeminal autonomic cephalgias (TACs), are frequently associated with neuro-ophthalmologic manifestations. Ophthalmologists are often the first physicians to be involved in the deciphering of headache-related visual disturbances. This article reviews two major primary headache disorders, migraine and trigeminal autonomic cephalgias, and discusses their neuro-ophthalmic complications, clinical presentation, and treatment.

Presentation, Natural History, and Management of Carotid Cavernous Aneurysms

We present the largest reported cohort of carotid cavernous aneurysms (CCA), comparing the neuro-ophthalmic presentation, complications, and outcome with and without endovascular treatment. Retrospective review of 185 patients with 206 CCAs examined between 1980 and 2001 at a tertiary neuro-ophthalmology and neurovascular service. Patients' symptoms and findings at presentation were recorded and compared with those at outcome. The effect of treatment on outcome and on complication rate was analyzed using the chi test, multivariate analysis of covariance, model-selection log-linear analysis, and multinomial logistic regression. Long-term follow-up was available for 189 of 206 CCAs. Seventy-four CCAs underwent treatment (endovascular, 67 [91%]; surgical treatment, 6 [9%]), and 115 were followed for an average of 4 years, two of which required later treatment. Treatment reduced the incidence and severity of pain, even after adjusting for the severity of initial pain (F(1,192 = 9.59, P = 0.002). Treatment did not significantly affect the patient's final diplopia after adjusting for their initial diplopia (F(1, 182 = 2.01, P = 0.158). Statistical examination revealed that the treated group had a higher proportion of neurological and visual complications than people who were not treated (2(2). = 25.26, P = 0.0003). Endovascular treatment of carotid cavernous aneurysms leads to a significantly higher rate of pain resolution compared with untreated patients, even after adjusting for initial pain severity. Diplopia may not resolve after treatment. The results of this study underscore our approach indicating treatment only in cases of debilitating pain, visual loss from compression, or diplopia in primary gaze or in patients with risk factors for major complications such as pre-existing coagulopathy or sphenoid sinus erosion.