Fluorescein Angiography Findings in Susac Syndrome: A Multicenter Retrospective Case Series.

BACKGROUND: Susac syndrome is a vasculopathy, resulting in the classic triad of branch retinal artery occlusion (BRAO), inner ear ischemia, and brain ischemia. In this retrospective chart review, we characterize fluorescein angiography (FA) findings and other ancillary studies in Susac syndrome, including the appearance of persistent disease activity and the occurrence of new subclinical disease on FA. METHODS: This multicenter, retrospective case series was institutional review board-approved and included patients with the complete triad of Susac syndrome evaluated with FA, contrasted MRI of the brain, and audiometry from 2010 to 2020. The medical records were reviewed for these ancillary tests, along with demographics, symptoms, visual acuity, visual field defects, and findings on fundoscopy. Clinical relapse was defined as any objective evidence of disease activity during the follow-up period after initial induction of clinical quiescence. The main outcome measure was the sensitivity of ancillary testing, including FA, MRI, and audiometry, to detect relapse. RESULTS: Twenty of the 31 (64%) patients had the complete triad of brain, retinal, and vestibulocochlear involvement from Susac syndrome and were included. Median age at diagnosis was 43.5 years (range 21-63), and 14 (70%) were women. Hearing loss occurred in 20 (100%), encephalopathy in 13 (65%), vertigo in 15 (75%), and headaches in 19 (95%) throughout the course of follow-up. Median visual acuity at both onset and final visit was 20/20 in both eyes. Seventeen (85%) had BRAO at baseline, and 10 (50%) experienced subsequent BRAO during follow-up. FA revealed nonspecific leakage from previous arteriolar damage in 20 (100%), including in patients who were otherwise in remission. Of the 11 episodes of disease activity in which all testing modalities were performed, visual field testing/fundoscopy was abnormal in 4 (36.4%), MRI brain in 2 (18.2%), audiogram in 8 (72.7%), and FA in 9 (81.8%). CONCLUSIONS: New leakage on FA is the most sensitive marker of active disease. Persistent leakage represents previous damage, whereas new areas of leakage suggest ongoing disease activity that requires consideration of modifying immunosuppressive therapy.

Splenium of the Corpus Callosum Infarct Associated With COVID-19: Case Report.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has been recently associated with infarction of the central splenium of the corpus callosum. These are described as cytotoxic lesions, and imaging rarely reveals enhancement. They have not been described in the body or head of the corpus callosum. Few diseases affect the corpus callosum, but the most common include multiple sclerosis, aquaporin-4 disease, and Susac syndrome. There is also emerging literature on Mild Encephalopathy with Reversible Splenial lesions associated with central and not basal lesions. The reason for the location of these lesions in acute COVID-19 infection is unknown. CASE REPORT: A 22-year-old female presented to the ED for altered mental status after being found down. A brief history review indicated that the patient had been altered for 2-3 days before being found naked and covered in her own feces and urine by her family after they had not heard from her. As she lived alone, a clear history of the events preceding her admission remains unclear. On initial assessment, the patient was found to be somnolent and nonverbal, though she could follow simple commands. On admission, testing for SARS CoV-2 RNA PCR was positive. Patient was admitted to the hospital for further work up to determine the cause of the altered mental status. CONCLUSION: We present a new case of a young woman who developed a central splenium lesion during acute COVID-19 infection and explain the predilection for the callosum in these patients, as well as literature to show that COVID-19 was most likely the cause.

Posterior Cortical Atrophy: Characteristics From a Clinical Data Registry.

Background: Posterior cortical atrophy (PCA) is a neurodegenerative syndrome that presents with higher-order visual dysfunction with relative sparing of memory and other cognitive domains, and it is most commonly associated with Alzheimer's disease pathology. There is a lack of data regarding the presentation of PCA to non-cognitive specialists. Therefore, we collected clinical data from neuro-ophthalmologists regarding the presentation of PCA to their practices and compared data to published cohorts and a published survey of cognitive specialists. Methods: Members of the North American Neuro-Ophthalmology Society Listserv (NANOSnet) were invited to complete an online, retrospective, chart-review data-entry survey regarding their patients with PCA, and REDCap was used for data collection. Results: Data for 38 patients were entered by 12 neuro-ophthalmologists. Patient mean age at presentation was 67.8 years, and 74% of patients were women. Difficulty reading was reported at presentation by 91% of patients, and poor performance on color vision, stereopsis, and visual field testing (performed reliably by 36/38 patients) were common findings. Most patients who were treated were treated with donepezil and/or memantine. Conclusions: Compared to published data from cognitive specialists, patients presenting to neuro-ophthalmology with PCA were more likely to be older and female and have a reading complaint. Reliable visual field testing was the norm with homonymous defects in the majority of patients. The neuro-ophthalmologist plays an important role in diagnosing PCA in older adults with unexplained visual signs and symptoms, and future studies of PCA should involve multiple specialists in order to advance our understanding of PCA and develop effective treatments.

Asymmetric Inferior Predilection of Lisch Nodules With Unilateral Ptosis.

Lisch nodules are melanocytic hamartomas that have been hypothesized to grow larger in the presence of sunlight. A 17-year-old boy with neurofibromatosis Type 1 and congenital ptosis in one eye presented and was found to have a distinct asymmetry of Lisch nodules between eyes with less under the ptotic lid. This case supports the theory that Lisch nodules form at least partially due to a direct trophic effect of sunlight.

Prevalence of Retinal Emboli and Acute Retinal Artery Occlusion in Acute Ischemic Stroke.

OBJECTIVE: In population-based studies asymptomatic retinal emboli occur in .32%-2.9% of people. Retinal artery occlusion (RAO) may occur concurrently with cerebral stroke but the frequency is unknown. No study has examined how commonly retinal emboli occur in the acute stroke population. We aimed to assess the prevalence of retinal emboli and RAO at the time of carotid territory ischemic stroke. METHODS: Patients were enrolled prospectively after onset of symptoms consistent with the diagnosis of carotid territory ischemic stroke. Every participant underwent pharmacologic dilation of both pupils and bedside funduscopic examination. Emboli were classified as cholesterol, calcific, platelet/fibrin, or other and categorized by the side of occurrence. Stroke was classified as atheroembolic, cardioembolic, embolic stroke of undetermined source, lacunar, or other. Acute RAO was diagnosed by direct visualization of ischemic retinal whitening. RESULTS: Sixty-five patients were enrolled with a mean age of 59.2 years; 23 were female (35.4%). Eleven of 65 subjects (16.9%) had retinal emboli visible on funduscopy; all were cholesterol emboli except a single platelet/fibrin embolus in a patient with atheroembolic source. Six patients (9%) had acute RAO and no RAO was seen in the lacunar or undetermined source subgroups. CONCLUSIONS: Retinal emboli occurred more than 10 times more frequently in the acute stroke patient than in large population-based studies. RAOs also occurred concurrently with ischemic stroke. Although emboli were seen in patients with atheroembolic and cardioembolic sources, all patients with carotid disease had emboli in the ipsilateral eye. Future studies are required to determine if the presence of retinal emboli or RAO may help elucidate an etiology in patients suffering from embolic stroke of undetermined source.

Diagnostic Criteria and Treatment Algorithm for Susac Syndrome.

BACKGROUND: Susac syndrome (SS) classically presents with the clinical triad of retinal artery occlusion, sensorineural hearing loss, and encephalopathy and the neuroimaging triad of white matter lesions, deep gray matter lesions, and leptomeningeal disease. However, patients can present with an incomplete clinical or neuroimaging triads making diagnosis difficult in certain situations. A standard treatment paradigm also is lacking in this illness. It is important for neuro-ophthalmologists to recognize clinical and radiographic findings that are pathognomonic for this syndrome and have a basic understanding of the available treatment options. EVIDENCE ACQUISITION: Review of medical literature. RESULTS: A definite diagnosis of SS is made when the clinical triad or the neuroimaging triad is present. There are numerous reports of 2 other imaging findings in this condition: arteriolar wall hyperfluorescence (AWH) on fluorescein angiography in retinal arterioles remote from retinal ischemia and central callosal lesions on MRI. Both of these imaging findings are diagnostic of SS. Gass plaques in retinal arterioles are almost always seen in the acute phase of the illness but are not pathognomonic for SS. The most common medications used in this syndrome are corticosteroids and intravenous immunoglobulin. A number of other medications have been used including mycopheolate, rituximab, azathioprine, and cyclophosphamide. CONCLUSIONS: In the absence of the clinical triad or magnetic resonance imaging triad for SS, AWH remote from retinal vascular injury and central callosal lesions are confirmatory of the diagnosis because they have never been described in any other condition. The presence of Gass plaques in retinal arterioles should strongly suggest the diagnosis. Despite the lack of clinical trial data, patients with SS must be treated promptly and aggressively. In more fulminant cases, addition of mycophenolate mofetil or rituximab is required, followed by cyclophosphamide when disease is refractory to other medications.

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.

Functional Vision Disorder.

Functional vision disorder (FVD) is a common problem seen in many neurologic and ophthalmologic practitioners' offices and may occur in isolation or in the presence of medical illness. This disorder presents with visual or oculomotor symptoms and manifests as vision loss in one or both eyes, visual field loss, double vision, oscillopsia, anisocoria, blepharospasm, or ptosis. Manual perimetry is the most effective method for determining functional visual loss, and the presence of a central scotoma in a functional visual field signifies that a neuropathophysiologic process is almost certainly present. The exact neuropathophysiologic mechanism of this disorder is unknown; however, information can be drawn from the small studies of FVD samples and studies examining neuropsychiatric factors in other conversion disorder semiologies. Psychological and psychiatric interventions can be useful in treating these patients.

Cauda equina involvement in Susac's syndrome.

Susac's syndrome is a rare autoimmune microangiopathy characterized by the clinical triad of encephalopathy, branch retinal artery occlusions, and sensorineural hearing loss. In many cases, the clinical triad is not fully present at the onset of symptoms. MRI studies often show characteristic punched out lesions of the central fibers of the corpus callosum, and leptomeningeal enhancement and deep gray matter lesions may also be seen. Here we present a case of Susac's syndrome in a middle aged man with the unique clinical finding of cauda equina syndrome and spinal MRI showing diffuse lumbosacral nerve root enhancement. Biopsy specimens of the brain, leptomeninges, and skin showed evidence of a pauci-immune endotheliopathy, consistent with pathology described in previous cases of Susac's syndrome. This case is important not only because it expands the clinical features of Susac's syndrome but also because it clarifies the mechanism of a disorder of the endothelium, an important target for many disorders of the nervous system.

Tadpole pupil.

Editors' Note: Dr. Egan inquires about the possibility of Tournay phenomenon in Kawasaki and Mayer's "Tadpole pupil." Dr. Charles, in reference to "Disease-modifying drugs for multiple sclerosis in pregnancy: A systematic review," suggests that it might be appropriate to continue glatiramer acetate in women trying to conceive given the lack of evidence of fetal risk. Authors Tremlett et al. advise that, at this point, each case should continue to be assessed individually.

Gass plaques and fluorescein leakage in Susac Syndrome.

INTRODUCTION: Susac Syndrome (SS) consists of the triad of encephalopathy, branch retinal artery occlusion, and hearing loss. It is an autoimmune endotheliopathy that primarily affects young women. Two funduscopic findings, Gass plaques (GP) and arteriolar wall hyperfluorescence (AWH), have recently been described and are not only useful in making the SS diagnosis but also point to the endothelium as the site of autoimmune injury. In this report we wish to raise awareness of GP and AWH with this disorder. METHODS: Four selected SS cases are presented with fundus photographs revealing GP. Fluorescein angiographic photographs are shown describing AWH. RESULTS: GP are shown in several cases. These GP are unique in that they are yellow, sometimes refractile, and located distant from retinal arteriolar bifurcations unlike Hollenhorst plaques which are orange and located at retinal arteriolar bifurcations. Fluorescein angiography displays AWH of the retinal arterioles of patients with SS distant from affected vessels which has not been demonstrated in other retinal vasculitides. CONCLUSION: Small punctuate yellow GP are almost unique to this disorder and their characteristic location and color should assist in confirming the diagnosis. Fluorescein angiography should be performed in all patients with an unexplained encephalopathy to look for the characteristic AWH pattern that occurs in this illness.