Pharmacologic Mydriasis Secondary to Topical Glycopyrronium Tosylate Cloths: Clinical Characterization From a Multicenter Analysis.

BACKGROUND: Topical glycopyrronium tosylate (GT) is an anticholinergic medication for treatment of axillary hyperhidrosis. Pharmacologic mydriasis and anisocoria from topical GT has been reported and may be underrecognized. This study aims to clinically characterize patients presenting with pharmacologic mydriasis from exposure to this medication. METHODS: This study is a retrospective observational case series. A multicenter chart review of 16 patients diagnosed with pharmacologic mydriasis secondary to topical GT was performed. RESULTS: Eight patients (50.0%) were age 18 years and younger, and 14 patients (87.5%) were female. Unilateral mydriasis (anisocoria) occurred in 14 patients (87.5%). Fourteen patients (87.5%) did not initially volunteer topical GT as a "medication," and the history of topical GT exposure needed to be elicited with further questioning. Hand hygiene details were known for 12 patients, and all reported that they did not wash their hands after GT application. Six patients (37.5%) were soft contact lens users. One patient had possible exposure through a family member's use of the medication. Ocular symptoms were common (blurry vision [11 patients, 68.8%] and eye dryness [7 patients, 43.8%]), but systemic anticholinergic symptoms were uncommon (such as constipation [1 patient, 6.3%] and urinary symptoms [3 patients, 18.8%]). CONCLUSIONS: Mydriasis associated with topical GT seems to be a consequence of local exposure rather than systemic toxicity. Because patients may not volunteer topical GT as a medication, eliciting a history of exposure often requires further specific questioning. Soft contact lens wear and poor postapplication hand hygiene seem to be associated with mydriasis in GT use.

Report on the Reunión Iberoamericana de Neuro-otologia 2018.

A report on the Reunión Iberoamericana de Neuro-otologia 2018 Fundacion Iberoamericana de Neuro-otologia.

Identification and validation of clinically meaningful benchmarks in the 12-item Multiple Sclerosis Walking Scale.

BACKGROUND: The 12-item Multiple Sclerosis Walking Scale (12-MSWS) is a validated questionnaire which assessed walking function; it has been widely adopted in multiple sclerosis (MS) clinical research. OBJECTIVE: Identify and validate clinically meaningful 12-MSWS benchmarks in MS. METHODS: Cross-sectional study of 159 MS patients permitted identification of clinically meaningful 12-MSWS benchmarks based on their relationship to real-life anchors. Identified 12-MSWS benchmarks were then validated in a second population of 96 subjects using measures of ambulation, cognition, and patient-reported outcomes. RESULTS: 12-MSWS score of 0-24.99 was associated with working outside the home and assistance-free mobility; 25-49.99 was associated with gait disability and difficulty doing housework; 50-74.99 was associated with unemployment, government healthcare, cane use, and difficulty performing instrumental activities of daily living (IADLs); and 75-100 was associated with change in occupation due to walking, mobility impairment requiring bilateral assistance, and inability to perform IADLs. During the validation step, strong linear associations were identified between 12-MSWS benchmarks and other MS-related disability outcome measures, including ambulatory and non-ambulatory measures. CONCLUSION: We have identified clinically meaningful 12-MSWS benchmarks which define four groups differentiated by increasing levels of mobility impairment and associated loss of functional independence. These data provide insight into how 12-MSWS translate to meaningful functional limitations in MS.

Fusiform Left Carotid-Ophthalmic Artery Aneurysm Presenting with Central Retinal Artery Occlusion.

Central retinal artery occlusion (CRAO) is a devastating ocular emergency characterized by acute painless visual loss in the ipsilateral eye. We describe the case of acute non-arteritic CRAO associated fusiform internal carotid-ophthalmic artery aneurysm with intraluminal thrombus. Despite the rarity of this condition, we suggest that carotid-ophthalmic artery aneurysm should be included in the differential diagnosis of CRAO.

Primary Ocular Adnexal Extranodal Marginal Zone Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma Presenting as Orbital Apex Syndrome.

A 75-year-old female with a past medical history significant for prior stroke and atrial fibrillation presented with acute onset of orbital apex syndrome with chemosis and periorbital ecchymosis. Following initial treatment to relieve intraocular pressure, she began spontaneously haemorrhaging retro-orbitally. Preliminary investigation with neuroimaging demonstrated a left orbital mass with extension into the orbital apex. A provisional diagnosis of cavernous haemangioma was made. She was treated with transorbital resection of the orbital mass. Subsequent histopathology revealed a diagnosis of ocular adnexal non-Hodgkin lymphoma of histologic type extranodal marginal zone of mucosa-associated lymphoid tissue (MALT lymphoma). MALT lymphoma should be considered in cases of orbital apex syndrome.

A Rare Case of Unilateral Progressive Vision Loss and Pachymeningitis.

We describe a 32-year-old man with presumed Vogt-Koyanagi Harada (VKH) syndrome, whose presenting symptoms were headache and progressive loss of vision in the right eye. Neuro-ophthalmic examination showed anterior and posterior uveitis, and retinal detachment in the right eye. Ocular coherence tomography (OCT) showed extensive submacular fluid in the right eye, while the fundus fluorescein angiogram (FFA) confirmed perifoveal retinal pigment epithelium (RPE) disruption and multifocal fluorescein leakage in the right eye. The brain MRI showed a small crescent of dependent fluid layering in the right posterior globe adjacent to the right optic nerve head, and pachymeningeal enhancement of the skull base dura along the clivus.This case demonstrates the utility of brain MRI and OCT findings in the early diagnosis of VKH syndrome, in the absence of prominent clinical signs of meningitis. Aggressive treatment is critical to preserve vision and prevent development of other systemic complications of the disease.

Using the Theories of Joseph Babinski to Manage Functional Vision Loss.

OBJECTIVE: To report our use of persuasion to treat patients with functional vision loss and to place them in the context of both Joseph Babinski's theories on hysteria and the current literature on management of functional vision loss. BACKGROUND: Conversion disorders, such as functional vision loss, can develop in response to a traumatic event. Recent functional imaging studies have found that, rather than being malingerers, patients with conversion disorders show changes within neuromodulatory pathways, suggesting organic dysfunction rather than a purely psychological disorder. METHODS: We conducted a retrospective analysis of 8 consecutive patients (7 female, 1 male; mean age 16 years) who had presented to a university-based neuro-ophthalmology clinic with vision loss from a conversion disorder. The patients had been given a lengthy visual task to perform at home, with the suggestion that their vision would improve by the time they completed the task. RESULTS: All 8 patients had evidence of a dissociation between real and perceived visual acuity and fields. All the patients performed the assigned visual task at home, and all either reported improvement or showed improved visual function at follow-up. CONCLUSIONS: A century after Joseph Babinski proposed using persuasion in managing patients with vision loss from a conversion disorder, we report that his method remains a viable and pathophysiologically sound option. Future case-controlled studies that include functional magnetic resonance imaging, other neurophysiologic imaging, and neuroradiographic evaluation may strengthen the correlation between persuasion therapy and recovery of normal vision.

Silent sinus syndrome.

PURPOSE OF REVIEW: Symptoms of diplopia, abnormal eyelid signs (retraction, ptosis, absent crease), ocular asymmetry (hypoglobus, enophthalmos), and dry eyes from lagophthalmos could all indicate the diagnosis of silent sinus syndrome. It is important for the physician to be updated on this relatively rare clinical entity. RECENT FINDINGS: Silent sinus syndrome lies on a spectrum of other forms of sinus-related orbitopathy. Uncommon presentations and descriptions of sinus involvement other than the maxillary sinus add to the variability of presentation. Radiographic features of disease include an opacified and hypoplastic sinus, a lateralized uncinate process, depression of the orbital floor, and a blocked osteomeatal complex. Management of silent sinus syndrome may include a single or multistage surgical approach, or a nonsurgical approach. SUMMARY: This review discusses silent sinus syndrome from a neuro-ophthalmological perspective.

The heidenhain variant of Creutzfeldt-Jakob disease--a case series.

BACKGROUND: To study the neuro-ophthalmologic characteristics of patients with the visual variant of Creuztfeldt-Jakob disease (CJD) predominantly affecting the occipital and parietal lobes, known as the Heidenhain variant (HvCJD). The initial symptoms and findings may overlap with other posterior cerebral degenerative disorders. We reviewed our experience with HvCJD including clinical course and results of neuroimaging, electroencephalography (EEG), and cerebrospinal fluid (CSF) studies. Neuropathological postmortem findings were reviewed when available to confirm the clinical impression. METHODS: Retrospective study of HvCJD patients examined in the past 15 years at a single tertiary referral university hospital. Rapid rate of visual and neurological deterioration and abnormal diffusion-weighted imaging (DWI) were characteristic for HvCJD. RESULTS: Three patients displayed abnormalities in DWI, EEG, and CSF and had rapid clinical progression, leading to a clinical diagnosis of HvCJD. None underwent diagnostic cerebral biopsy. In 2 patients, the diagnosis of sporadic CJD was confirmed by postmortem neuropathologic, immunohistochemical, and genetic studies. CONCLUSIONS: The gold standard for establishing the diagnosis of HvCJD is based on the characteristic histopathologic findings and molecular confirmation. Concern with potential iatrogenic CJD, related to surgical instrumentation or operating room prion contamination, has limited the availability of confirmatory brain biopsy. Our case series illustrates how the combination of clinical neuroimaging and EEG studies and 14:3:3 protein and other neuronal protein marker levels can lead to the diagnosis of HvCJD. Immunohistochemical analysis and genetic testing at a specialized prion research center will assist in identifying the sporadic variant and genetic forms of CJD.

Quantitative video-oculography to help diagnose stroke in acute vertigo and dizziness: toward an ECG for the eyes.

BACKGROUND AND PURPOSE: Strokes can be distinguished from benign peripheral causes of acute vestibular syndrome using bedside oculomotor tests (head impulse test, nystagmus, test-of-skew). Using head impulse test, nystagmus, test-of-skew is more sensitive and less costly than early magnetic resonance imaging for stroke diagnosis in acute vestibular syndrome but requires expertise not routinely available in emergency departments. We sought to begin standardizing the head impulse test, nystagmus, test-of-skew diagnostic approach for eventual emergency department use through the novel application of a portable video-oculography device measuring vestibular physiology in real time. This approach is conceptually similar to ECG to diagnose acute cardiac ischemia. METHODS: Proof-of-concept study (August 2011 to June 2012). We recruited adult emergency department patients with acute vestibular syndrome defined as new, persistent vertigo/dizziness, nystagmus, and (1) nausea/vomiting, (2) head motion intolerance, or (3) new gait unsteadiness. We recorded eye movements, including quantitative horizontal head impulse testing of vestibulo-ocular-reflex function. Two masked vestibular experts rated vestibular findings, which were compared with final radiographic gold-standard diagnoses. Masked neuroimaging raters determined stroke or no stroke using magnetic resonance imaging of the brain with diffusion-weighted imaging obtained 48 hours to 7 days after symptom onset. RESULTS: We enrolled 12 consecutive patients who underwent confirmatory magnetic resonance imaging. Mean age was 61 years (range 30-73), and 10 were men. Expert-rated video-oculography-based head impulse test, nystagmus, test-of-skew examination was 100% accurate (6 strokes, 6 peripheral vestibular). CONCLUSIONS: Device-based physiological diagnosis of vertebrobasilar stroke in acute vestibular syndrome should soon be possible. If confirmed in a larger sample, this bedside eye ECG approach could eventually help fulfill a critical need for timely, accurate, efficient diagnosis in emergency department patients with vertigo or dizziness who are at high risk for stroke.

Validation of patient determined disease steps (PDDS) scale scores in persons with multiple sclerosis.

BACKGROUND: The Patient Determined Disease Steps (PDDS) is a promising patient-reported outcome (PRO) of disability in multiple sclerosis (MS). To date, there is limited evidence regarding the validity of PDDS scores, despite its sound conceptual development and broad inclusion in MS research. This study examined the validity of the PDDS based on (1) the association with Expanded Disability Status Scale (EDSS) scores and (2) the pattern of associations between PDDS and EDSS scores with Functional System (FS) scores as well as ambulatory and other outcomes. METHODS: 96 persons with MS provided demographic/clinical information, completed the PDDS and other PROs including the Multiple Sclerosis Walking Scale-12 (MSWS-12), and underwent a neurological examination for generating FS and EDSS scores. Participants completed assessments of cognition, ambulation including the 6-minute walk (6 MW), and wore an accelerometer during waking hours over seven days. RESULTS: There was a strong correlation between EDSS and PDDS scores (ρ = .783). PDDS and EDSS scores were strongly correlated with Pyramidal (ρ = .578 &ρ = .647, respectively) and Cerebellar (ρ = .501 &ρ = .528, respectively) FS scores as well as 6 MW distance (ρ = .704 &ρ = .805, respectively), MSWS-12 scores (ρ = .801 &ρ = .729, respectively), and accelerometer steps/day (ρ = -.740 &ρ = -.717, respectively). CONCLUSION: This study provides novel evidence supporting the PDDS as valid PRO of disability in MS.

Neuro-ophthalmologic side-effects of systemic medications.

PURPOSE OF REVIEW: Systemic medications may cause side-effects manifesting primarily as neuro-ophthalmologic problems. It is paramount for the physician to be updated on both well recognized and novel associations between drugs and their potential adverse reactions. RECENT FINDINGS: There is a growing list of medications that can cause pupil dilation, pupil constriction, dyschromatopsia, worsening of ocular myasthenia gravis, posterior reversible leukoencephalopathy syndrome, pseudotumor cerebri, disturbances in eye movements, accommodation problems, or optic neuropathy. This is partly due to the increasing number of drugs available in each class, but also to the increased recognition of neuro-ophthalmological disorders. SUMMARY: This review discusses neuro-ophthalmological problems and the medications that may precipitate them.

Further validation of multiple sclerosis walking scale-12 scores based on spatiotemporal gait parameters.

OBJECTIVE: To examine the association between Multiple Sclerosis Walking Scale-12 (MSWS-12) scores and spatiotemporal parameters of gait as indicators of gait quality among ambulatory persons with multiple sclerosis (MS). DESIGN: Cross-sectional study. SETTING: University research laboratory. PARTICIPANTS: Community-residing persons with MS (N=268). INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Main outcome measures included the MSWS-12 and spatial and temporal gait parameters (walking speed, cadence, step length, step time, base of support [ie, the distance between 1 footfall and the line of progression of the opposing foot], and percentage of gait cycle spent in double support). Secondary outcomes included the timed 25-foot walk (T25FW), 6-minute walk (6MW), and Patient-Determined Disease Steps scale. RESULTS: MSWS-12 scores were significantly correlated with walking speed (r=-.59), cadence (r=-.50), step length (r=-.53), step time (r=.46), base of support (r=.29), and percentage of the gait cycle spent in double support (r=.54). MSWS-12 scores further were significantly correlated with T25FW (r=.57) and 6MW (r=-.75) scores. CONCLUSIONS: Such findings suggest that the MSWS-12 captures aspects of walking quality, assessed as spatiotemporal parameters of gait, in addition to walking speed and endurance in persons with MS.

Cortical vision loss as a prominent feature of H1N1 encephalopathy.

A 20-year-old woman infected with the 2009 H1N1 strain of influenza A developed bilateral visual loss. Brain MRI showed restricted diffusion of the parietal and occipital lobes, and her spinal fluid did not contain inflammatory cells. This report describes an unusual case of H1N1 influenza A virus infection primarily affecting the posterior visual pathways.

Radiology update in neuro-ophthalmology.

PURPOSE OF REVIEW: Radiologic imaging is indispensible for the diagnosis and management of many neuro-ophthalmologic conditions. Advances in the radioimaging of neuro-ophthalmologic disorders may evolve from the clinical or the radiological side, meaning there is a constant stream of new information for the clinician. RECENT FINDINGS: Functional MRI, diffusion tensor MRI, magnetization transfer imaging, and magnetic resonance spectroscopy are examples of nonstandard radiographic techniques, which have expanded the knowledge of neuro-ophthalmologic conditions. Studies using conventional MRI have also led to advances in understanding optic neuropathies, the ocular motor system, pseudotumor cerebri, posterior reversible encephalopathy syndrome and migraine. SUMMARY: This article discusses recent radiologic advances relevant to neuro-ophthalmology.

Walking and thinking in persons with multiple sclerosis who vary in disability.

OBJECTIVE: To examine the effect of a cognitive task on spatiotemporal parameters of gait in persons with multiple sclerosis (MS) with varying disability. DESIGN: Cohort. SETTING: Testing occurred at a local hospital. PARTICIPANTS: Community-living persons (N=78) with MS participated in this investigation. They were divided into 3 groups based on Expanded Disability Status Scale (EDSS) scores: mild (2.0-3.5 EDSS; n=21); moderate (4.0-5.5 EDSS; n=25); and severe (6.0-6.5 EDSS; n=32). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Participants walked at a self-selected pace on an electronic pathway, which recorded spatiotemporal parameters of gait, in 4 separate trials and completed a cognitive task in the last 2 trials. The effect of the cognitive task was quantified as the change in spatiotemporal parameters of gait. RESULTS: There was an overall decline in gait with the additive cognitive task. The magnitude of the adverse changes ranged from 1.8% for step length (P=.02) to 12% for gait velocity (P<.001). Moreover, adverse changes in gait function were greatest in the severe and moderate disability group (P<.05). CONCLUSIONS: Persons with MS have impaired walking while doing a cognitive task, and the adverse effect of a cognitive task on walking function is greatest in persons with severe and moderate disability. Difficulty walking while thinking has implications for everyday life and may be related to the risk of falls. Further work is needed to determine whether the adverse effect of an additive cognitive task can be minimized with rehabilitative interventions.

Clinical course of patients with ophthalmoplegia caused by radiographically detectable brainstem demyelination occurring as a clinically isolated demyelinating syndrome.

BACKGROUND: Demyelinating brainstem lesions often causing ophthalmoplegia may occur as the first manifestation of a clinically isolated demyelinating syndrome (CIS). CIS could be the initial attack of clinically definite multiple sclerosis (CDMS) should a second symptomatic attack occur. We report a series of patients with ophthalmoplegia occurring as CIS and assess potential factors affecting the clinical course and final outcome. METHODS: A computer search was performed for patients evaluated in a university academic neurology practice to identify those with the diagnosis of diplopia. Selection was then made of patients who met the criteria for CIS, and these individuals formed the basis of this study. RESULTS: Ten of 327 patients presenting with diplopia fulfilled inclusion criteria. Of these, all had ophthalmoplegia in primary position of gaze or symptomatic internuclear ophthalmoplegia, and all recovered irrespective of brain MRI findings, steroid use, presence of oligoclonal bands, or progression to CDMS. CONCLUSION: The ophthalmoplegia of CIS tends to improve with time, regardless of later progression to CDMS. More analysis is needed to fully understand this unique presentation of demyelination.

Retinal Nerve Fibre Layer and Macular Thinning in Spinocerebellar Ataxia and Cerebellar Multisystem Atrophy.

The spinocerebellar ataxias, like all neurodegenerative diseases, lack objective disease- and stage-specific biomarkers. Based on reports of clinically evident optic disc atrophy or retinal disease in some ataxia patients, and the discovery that pre-symptomatic retinal thinning occurs in other neurologic diseases such as multiple sclerosis, we tested the hypothesis that subclinical neuronal or axonal loss in the retina could occur in the degenerative ataxias. Spectral domain optical coherence tomography was performed on 29 ataxia patients with genetically proven spinocerebellar ataxia (SCA) 1, 2, 3, or 6, or multisystem atrophy type C (MSA-C) and 27 age-matched normal subjects. Ataxia patients were assessed using the scale for assessment and rating of ataxia. Compared with normal control subjects, retinal nerve fibre layer (RNFL) thickness was reduced for patients with SCA2 and SCA3, and thickness in the macular region was reduced for all SCAs but SCA2.

Ophthalmologic features of the common spinocerebellar ataxias.

PURPOSE OF REVIEW: The spinocerebellar ataxias (SCAs) are a phenotypically and genetically diverse group of autosomal dominant disorders that cause pathological degeneration in the cerebellum, brainstem, and retina, resulting in a wide variety of ophthalmologic signs and symptoms. RECENT FINDINGS: The genetic discrimination of the SCAs has advanced dramatically over the past decade. The most common genetic (mutational) mechanism for the SCAs is an abnormal expansion to a stretch of glutamine amino acid residues (polyglutamine tract) encoded by any of several SCA-causing genes. Knowledge regarding the pathophysiology of polyglutamine-expansion-induced protein dysfunction is an area of intense investigation. SUMMARY: The ophthalmologist may be the first to encounter a patient with SCA, and a review of the most common genetic subtypes of this disorder is helpful in diagnosis and management.