Accuracy of Repetitive Ocular Vestibular-Evoked Myogenic Potentials to Diagnose Myasthenia Gravis in Patients With Ptosis or Diplopia.

BACKGROUND AND OBJECTIVES: We developed repetitive ocular vestibular-evoked myogenic potentials (roVEMP) as an electrophysiologic test that allows us to elicit the characteristic decrement of extraocular muscles in patients with ocular myasthenia gravis (OMG). Case-control studies demonstrated that roVEMP reliably differentiates patients with OMG from healthy controls. We now aimed to evaluate the diagnostic accuracy of roVEMP for OMG diagnosis in patients with ptosis and/or diplopia. METHODS: In this blinded prospective diagnostic accuracy trial, we compared roVEMP in 89 consecutive patients presenting with ptosis and/or diplopia suspicious of OMG with a multimodal diagnostic approach, including clinical examination, antibodies, edrophonium testing, repetitive nerve stimulation of accessory and facial nerves, and single-fiber EMG (SFEMG). We calculated the roVEMP decrement as the ratio between the mean of the first 2 responses compared with the mean of the sixth-ninth responses in the train and used cutoff of >9% (unilateral decrement) in a 30 Hz stimulation paradigm. RESULTS: Following a complete diagnostic work-up, 39 patients (44%) were diagnosed with ocular MG, while 50 patients (56%) had various other neuro-ophthalmologic conditions, but not MG (non-MG). roVEMP yielded 88.2% sensitivity, 30.2% specificity, 50% positive predictive value (PPV), and 76.5% negative predictive value (NPV). For comparison, SFEMG resulted in 75% sensitivity, 56% specificity, 55.1% PPV, and 75.7% NPV. All other diagnostic tests (except for the ice pack test) also yielded significantly higher positive results in patients with MG compared with non-MG. DISCUSSION: The study revealed a high sensitivity of 88.2% for roVEMP in OMG, but specificity and PPV were too low to allow for the OMG diagnosis as a single test. Thus, differentiating ocular MG from other neuro-ophthalmologic conditions remains challenging, and the highest diagnostic accuracy is still obtained by a multimodal approach. In this study, roVEMP can complement the diagnostic armamentarium for the diagnosis of MG. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that in patients with diplopia and ptosis, roVEMP alone does not accurately distinguish MG from non-MG disorders. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov: NCT03049956.

Using Smartphone Exophthalmometry to Measure Eyeball Protrusion.

Importance: The current clinical criterion standard for measuring abnormal eyeball protrusion is still the historic Hertel exophthalmometer, which is prone to reading errors. Therefore, a smartphone application has been developed to measure exophthalmos. Objective: To evaluate a relatively simple noninvasive measurement method for exophthalmos using a smartphone. Design, Setting, and Participants: This cross-sectional study compared smartphone exophthalmometry with the existing reference standard, the Hertel exophthalmometer, or a professional high-resolution 3-dimensional scanner. Participants were patients with exophthalmos due to Graves orbitopathy and other intraorbital conditions and healthy volunteers who were recruited between June 2019 and January 2022 from the Department of Ophthalmology, University Hospital Zurich. Interventions: All participants were examined twice by 3 different operators using 3 different methods (smartphone, high-resolution scanner, or Hertel exophthalmometer) at an interval of a minimum of 2 weeks or after exophthalmos-changing treatment. Main Outcome Measures: Accuracy and precision, test-retest reliability, and interoperator reliability of eyeball protrusion measurements obtained with the smartphone compared to the Hertel exophthalmometer and the high-resolution face scanner. Results: Of 39 participants, 23 patients (median [IQR] age, 54 [44-59] years; 15 [65%] female and 8 [35%] male) showed a mean difference in eyeball protrusion of 3.3 mm and 16 healthy volunteers (median [IQR] age, 32 [30-37] years; 11 [69%] female and 5 [31%] male) of 0.8 mm without any significant difference between the 3 methods. Accuracy and precision agreement between exophthalmos measures with the smartphone and the Hertel exophthalmometer showed an intraclass correlation coefficient (ICC) of 0.89 (95% CI, 0.80-0.94) and 0.93 (95% CI, 0.83-0.97) for the high-resolution scanner. Interoperator agreement was highest for the high-resolution scanner (ICC, 0.99 [95% CI, 0.98-0.99]), followed by the smartphone (ICC, 0.95 [95% CI, 0.92-0.97]) and the Hertel exophthalmometer (ICC, 0.91 [95% CI, 0.85-0.95]). Test retest reliability was similarly high for the smartphone (ICC, 0.93 [95% CI, 0.82-0.95]), the Hertel exophthalmometer (ICC, 0.92 [95% CI, 0.83-0.96]), and the high-resolution scanner (ICC, 0.95 [95% CI, 0.89-0.97]). Conclusions and Relevance: The findings of this study demonstrate relatively high accuracy and precision, interoperator reliability, and test-retest reliability for smartphone exophthalmometry. These data support the use of a smartphone in place of a Hertel exophthalmometer for measuring exophthalmos in the future.

The "Eyelet Sign" as an MRI Clue for Inflammatory Brown Syndrome.

BACKGROUND: Brown syndrome is characterized by a restrictive elevation deficit of the affected eye in adduction. Besides the well-known congenital form, different acquired etiologies including inflammation, trauma, and surgery may prevent the superior oblique (SO) tendon from gliding freely through the trochlea on attempted upgaze. We present MRI findings in pediatric and adult patients with inflammatory acquired Brown syndrome. METHODS: Retrospective review of clinical and MRI findings of 6 patients (4 children: median age 8.4 years [range 6.1-8.7]; 2 adults: age 46.4 and 51.1 years). Median follow-up was 23 months (range 1-52). RESULTS: In all 6 patients, orbital MRI demonstrated inflammatory changes of the SO tendon-trochlea complex. A striking feature was circumferential contrast enhancement of the trochlea with central sparing where the tendon passes, reminiscent of an eyelet. In all cases, the motility restriction improved either spontaneously or with systemic anti-inflammatory treatment. Although both adult patients had a history of known seronegative spondyloarthritis, there was no associated systemic condition in the children in our series. CONCLUSIONS: Both in children and in adults, MRI can provide evidence of inflammatory changes located at the trochlea-tendon complex in acquired Brown syndrome here referred to as the "eyelet sign," which may be helpful in confirming the clinical diagnosis and guide appropriate treatment.

Widespread White Matter Alterations in Patients With Visual Snow Syndrome.

Background: Visual snow is considered a disorder of central visual processing resulting in a perturbed perception of constant binocular flickering or pixilation of the whole visual field. The underlying neurophysiological and structural alterations remain elusive. Methods: In this study, we included patients (final n = 14, five dropouts; five females, mean age: 32 years) with visual snow syndrome (VSS) and age- and sex-matched controls (final n = 20, 6 dropouts, 13 females, mean age: 28.2 years). We applied diffusion tensor imaging to examine possible white matter (WM) alterations in patients with VSS. Results: The patient group demonstrated higher (p-corrected < 0.05, adjusted for age and sex) fractional anisotropy (FA) and lower mean diffusivity (MD) and radial diffusivity (RD) compared to controls. These changes were seen in the prefrontal WM (including the inferior fronto-occipital fascicle), temporal and occipital WM, superior and middle longitudinal fascicle, and sagittal stratum. When additionally corrected for migraine or tinnitus-dominant comorbidities in VSS-similar group differences were seen for FA and RD, but less pronounced. Conclusions: Our results indicate that patients with VSS present WM alterations in parts of the visual cortex and outside the visual cortex. As parts of the inferior fronto-occipital fascicle and sagittal stratum are associated with visual processing and visual conceptualisation, our results suggest that the WM alterations in these regions may indicate atypical visual processing in patients with VSS. Yet, the frequent presence of migraine and other comorbidities such as tinnitus in VSS makes it difficult to attribute WM disruptions solely to VSS.

Divergence bias in Hess compared to Harms screen strabismus testing.

The Hess and the Harms screen test each have different testing distances. While the Harms screen test is usually performed at 2.5 m, the Hess screen test is performed at 0.5 m. The geometry of the closer testing distance of the Hess screen test requires an increase of the convergence angle by 6°. This study investigates the quantitative differences between the two frequently employed screen tests. Ocular deviation of 18 normal subjects and 36 patients with congenital or acquired paralytic or concomitant strabismus were assessed with a complete orthoptic examination including alternate prism cover testing at near (nPCT) and far (fPCT), as well as Hess and Harms screen testing. One-way ANOVA was used for statistical analysis. The Hess test recorded more overall exodeviation compared to the Harms test for patients (mean difference -3.50°, 95% limits of agreement (CI) = [-4.79, -2.21], p < .001), and controls (mean difference -1.78°, CI = [-2.99, -0.56], p = .004). For vertical deviations, there was no statistically significant difference between the two tests for patients (mean difference +0.75°, CI = [-0.41, +1.91], p = .251), and controls (mean difference -0.28°, CI = [-0.68, -0.11], p = 0.231). This study emphasizes the importance to consider the divergence bias when comparing the Hess to the Harms screen test, which is likely explained by the greater vergence demand dependent on the closer testing distance. The exodeviation shift tended to be more pronounced in patients than controls, which may imply that patients with strabismus have an impaired convergence drive.

Abnormal Connectivity and Brain Structure in Patients With Visual Snow.

OBJECTIVE: Visual snow (VS) is a distressing, life-impacting condition with persistent visual phenomena. VS patients show cerebral hypermetabolism within the visual cortex, resulting in altered neuronal excitability. We hypothesized to see disease-dependent alterations in functional connectivity and gray matter volume (GMV) in regions associated with visual perception. METHODS: Nineteen patients with VS and 16 sex- and age-matched controls were recruited. Functional magnetic resonance imaging (fMRI) was applied to examine resting-state functional connectivity (rsFC). Volume changes were assessed by means of voxel-based morphometry (VBM). Finally, we assessed associations between MRI indices and clinical parameters. RESULTS: Patients with VS showed hyperconnectivity between extrastriate visual and inferior temporal brain regions and also between prefrontal and parietal (angular cortex) brain regions (p < 0.05, corrected for age and migraine occurrence). In addition, patients showed increased GMV in the right lingual gyrus (p < 0.05 corrected). Symptom duration positively correlated with GMV in both lingual gyri (p < 0.01 corrected). CONCLUSION: This study found VS to be associated with both functional and structural changes in the early and higher visual cortex, as well as the temporal cortex. These brain regions are involved in visual processing, memory, spatial attention, and cognitive control. We conclude that VS is not just confined to the visual system and that both functional and structural changes arise in VS patients, be it as an epiphenomenon or a direct contributor to the pathomechanism of VS. These in vivo neuroimaging biomarkers may hold potential as objective outcome measures of this so far purely subjective condition.

Diagnosing Myasthenia Gravis With Repetitive Ocular Vestibular Evoked Myogenic Potentials.

Timely and accurate diagnosis of myasthenia gravis, particularly in patients with fluctuating, isolated ocular involvement, remains challenging. Serological antibody testing and repetitive nerve stimulation of peripheral muscles usually have low sensitivity in these patients. Edrophonium testing may cause adverse events, single-fiber electromyography (SFEMG) is time-consuming and both tests are often unavailable outside specialized institutions. Repetitive ocular vestibular evoked myogenic potential (roVEMP) stimulation has recently been introduced to facilitate the diagnosis of myasthenia gravis. Similar to repetitive nerve stimulation, roVEMPs detect muscle decrements with the benefit of being non-invasive and allowing for direct measurement of the extraocular muscles. This review summarizes the clinical evidence of the diagnostic value of roVEMP for myasthenia. Prospective clinical trials have demonstrated high sensitivity and specificity. RoVEMPs are of particular interest in challenging myasthenia subgroups with isolated ocular involvement, negative serology, and/or negative conventional electrophysiological results. Optimal roVEMP repetition rates of 20-30 Hz have been identified. This promising novel diagnostic tool merits further attention and investigation to establish its value as a clinical test for myasthenia.

Long-Term Follow-Up in Children with Anisocoria: Cocaine Test Results and Patient Outcome.

BACKGROUND: Evaluation of anisocoria including pharmacological testing for Horner's syndrome in the pediatric population is challenging in view of potential serious underlying disease. We describe cocaine test results, outcome of systemic investigation, and long-term follow-up in children with anisocoria. METHODS: Retrospective review of medical records and phone interview of consecutive pediatric patients (<18 years old) who underwent cocaine testing from August 2007 to July 2015 at a tertiary referral centre. RESULTS: A total of 35 patients were included with a positive, negative, or inconclusive cocaine test in 12/35, 19/35, and 4/35, respectively. Systemic investigation was performed in 11 of the patients with a positive and in 2 of the patients with an inconclusive cocaine test result. Mediastinal Hodgkin lymphoma was found in one patient with an inconclusive cocaine test result. Two other cases were presumably related to birth trauma and surgical trauma. None of the other children further developed any pathology during the follow-up period of 34.8 months (range 0-106.6). CONCLUSIONS: In most children with anisocoria and a positive cocaine test result, systemic investigation did not reveal any underlying etiology. The only malignant disease was diagnosed in a patient with a suspicion of Horner's syndrome but with an inconclusive cocaine test result in our cohort.

Treatment of esophageal variceal hemorrhage with self-expanding metal stents as a rescue maneuver in a swiss multicentric cohort.

Acute esophageal variceal bleeding in patients with portal hypertension remains a complication with a high mortality today. In cases refractory to standard therapy including endoscopic band ligation and pharmacological therapy, traditionally balloon tamponade has been used as salvage therapy. However, these techniques show several important limitations. Self-expanding metal stents (SEMS) have been proposed as an alternative rescue treatment. The use of variceal stenting in 7 patients with a total of 9 bleeding episodes in three different Swiss hospitals is demonstrated. While immediate bleeding control is achieved in a high percentage of cases, the 5-day and 6-week mortality rate remain high. Mortality is strongly influenced by the severity of the underlying liver disease. Accordingly, our data represent a high-risk patient collective. Thanks to their safety and easy handling, SEMS are an interesting alternative to balloon tamponade as a bridging intervention to definitive therapy including the pre-hospital setting.

The morphology of anisotropic 3D-printed hydroxyapatite scaffolds.

Three-dimensional (3D) scaffolds with tailored pores ranging from the nanometer to millimeter scale can support the reconstruction of centimeter-sized osseous defects. Three-dimensional-printing processes permit the voxel-wise fabrication of scaffolds. The present study rests upon 3D-printing with nano-porous hydroxyapatite granulates. The cylindrical design refers to a hollow bone with higher density at the periphery. The millimeter-wide central channel follows the symmetry axis and connects the perpendicularly arranged micro-pores. Synchrotron radiation-based micro computed tomography has served for the non-destructive characterization of the scaffolds. The 3D data treatment is essential, since, for example, the two-dimensional distance maps overestimate the mean distances to the material by 33-50% with respect to the 3D analysis. The scaffolds contain 70% micrometer-wide pores that are interconnected. Using virtual spheres, which might be related to the cells migrating along the pores, the central channel remains accessible through the micro-pores for spheres with a diameter of up to (350+/-35)mum. Registering the tomograms with their 3D-printing matrices has yielded the almost isotropic shrinking of (27+/-2)% owing to the sintering process. This registration also allows comparing the design and tomographic data in a quantitative manner to extract the quality of the fabricated scaffolds. Histological analysis of the scaffolds seeded with osteogenic-stimulated progenitor cells has confirmed the suitability of the 3D-printed scaffolds for potential clinical applications.