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.

Lesion follows function: video-oculography compared with MRI to diagnose internuclear ophthalmoplegia in patients with multiple sclerosis.

BACKGROUND: Video-oculography (VOG) is used to quantify functional deficits in internuclear ophthalmoplegia (INO), whereas MRI can detect the corresponding structural lesions in the medial longitudinal fasciculus (MLF). This study investigates the diagnostic agreement of MRI compared to VOG measurements. METHODS: We prospectively compared structural MRI findings and functional VOG measures of 63 MS patients to assess their diagnostic agreement for INO. RESULTS: MRI detected 12 true-positive and 92 true-negative MLF lesions for INO compared to VOG (12 true-positive and 38 true-negative patients) but identified one-third of the MLF lesions on the wrong side. MRI ratings were specific (92.0%) to detect MLF lesions but not sensitive (46.2%) for diagnosing INO (86.4% and 63.2% by patient). Accordingly, MRI has a high positive likelihood ratio of 5.77 but a modest negative likelihood ratio of 0.59 for the probability of INO (4.63 and 0.43) with an accuracy of 82.5% (79.4%). CONCLUSION: MRI assessments are highly specific but not sensitive for detecting INO compared to VOG. While MRI identifies MLF lesions in INO, VOG quantifies the deficit. As a simple, quick, and non-invasive test for diagnosing and tracking functional INO deficits, it will hopefully find its place in the diagnostic and therapeutic pathways of MS.

[CME: Idiopathic Intracranial Hypertension]. / CME: Idiopathische intrakranielle Hypertension.

CME: Idiopathic Intracranial Hypertension Abstract. Idiopathic intracranial hypertension is a pressure-induced secondary headache disorder and optic neuropathy. It primarily affects obese women of childbearing age and poses an interdisciplinary challenge both diagnostically and therapeutically. The most common symptom of this disorder are headaches frequently accompanied by photo- and/or phonophobia, whose semiology often resembles that of migraine, followed by transient visual obscurations and pulsatile tinnitus. While protection of visual acuity and visual fields are of first therapeutical priority, adequate headache treatment also plays a key role. In the majority of cases, conservative treatment including weight loss and pharmacological therapy is sufficient. In case of a fulminant disease course or loss of visual function, interventional strategies can be applied additionally. Headache treatment is guided by the predominant semiology.

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.

Pre-habilitation Before Vestibular Schwannoma Surgery-Impact of Intratympanal Gentamicin Application on the Vestibulo-Ocular Reflex.

Background: Patients with vestibular schwannoma that show residual peripheral-vestibular function before surgery may experience sudden and substantial vestibular loss of function after surgical resection. To alleviate the sudden loss of peripheral-vestibular function after vestibular-schwannoma (VS) resection, pre-surgical intratympanic gentamicin application was proposed. Objective: We hypothesized that this approach allows for a controlled reduction of peripheral-vestibular function before surgery but that resulting peripheral-vestibular deficits may be canal-specific with anterior-canal sparing as observed previously in systemic gentamicin application. Methods: Thirty-four patients (age-range = 27-70 y) with unilateral VS (size = 2-50 mm) were included in this retrospective single-center trial. The angular vestibulo-ocular reflex (aVOR) was quantified before and after (29.7 ± 18.7 d, mean ± 1SD) a single or two sequential intratympanic gentamicin applications by use of video-head-impulse testing. Both aVOR gains, cumulative saccadic amplitudes, and overall aVOR function were retrieved. Statistical analysis was done using a generalized linear model. Results: At baseline, loss of function of the horizontal (20/34) and posterior (21/34) canal was significantly (p < 0.001) more frequent than that of the anterior canal (5/34). After gentamicin application, loss of function of the horizontal (32/34) or posterior (31/34) canal remained significantly (p ≤ 0.003) more frequent than that of the anterior canal (18/34). For all ipsilesional canals, significant aVOR-gain reductions and cumulative-saccadic-amplitude increases were noted after gentamicin. For the horizontal canal, loss of function was significantly larger (increase in cumulative-saccadic-amplitude: 1.6 ± 2.0 vs. 0.8 ± 1.2, p = 0.007) or showed a trend to larger changes (decrease in aVOR-gain: 0.24 ± 0.22 vs. 0.13 ± 0.29, p = 0.069) than for the anterior canal. Conclusions: Intratympanic gentamicin application resulted in a substantial reduction in peripheral-vestibular function in all three ipsilesional canals. Relative sparing of anterior-canal function noted at baseline was preserved after gentamicin treatment. Thus, pre-surgical intratympanic gentamicin is a suitable preparatory procedure for reducing the drop in peripheral-vestibular function after VS-resection. The reasons for relative sparing of the anterior canal remain unclear.

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.

Corrective Saccades in Unilateral and Bilateral Vestibular Hypofunction During Slow Rotation Expressed by Visually Enhanced VOR and VOR Suppression: Role of the Cerebellum.

In clinical practice, the head impulse test paradigm (HIMP) and the suppression head impulse paradigm (SHIMP) stimulate high-frequency head movements so that the visual system is temporarily suppressed. The two tests could also be useful tools for vestibular assessment at low frequencies: VVOR (visually enhanced vestibulo-ocular reflex) and VORS (vestibulo-ocular reflex suppression). The aim of this study is to analyze the eye movements typically found during VVOR and VORS testing in patients with unilateral and bilateral vestibular hypofunction. Twenty patients with unilateral vestibular hypofunction, three patients with bilateral vestibular hypofunction, and ten patients with normal vestibular function (control group) were analyzed through VVOR and VORS testing with an Otometrics ICS Impulse system. During the VVOR test, patients with unilateral vestibular hypofunction exhibited corrective saccades to the same direction of the nystagmus fast phase toward the healthy side when the head rotates toward the affected side, while patients with bilateral vestibular hypofunction exhibited corrective saccades to the opposite side of head movements to each side. During the VORS test, patients with unilateral vestibular hypofunction seem to exhibit larger corrective saccades to the healthy side when the head was moved to this side, while patients with bilateral vestibular hypofunction did not exhibit corrective saccades during head movements to either side. Our data suggest that the VVOR and VORS tests yield the same diagnostic information as the HIMP and SHIMP tests in unilateral and bilateral vestibular hypofunction, and can contribute to the diagnosis of a peripheral vestibular loss as well as the affected side.

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.

Vestibular mapping in patients with unilateral peripheral-vestibular deficits.

OBJECTIVE: To test the hypothesis that patterns of semicircular canal (SCC) and otolith impairment in unilateral vestibular loss depend on the underlying disorders, we analyzed peripheral-vestibular function of all 5 vestibular sensors. METHODS: For this retrospective case series, we screened the hospital video-head-impulse test database (n = 4,983) for patients with unilaterally impaired SCC function who also received ocular vestibular-evoked myogenic potentials and cervical vestibular-evoked myogenic potentials (n = 302). Frequency of impairment of vestibular end organs (horizontal/anterior/posterior SCC, utriculus/sacculus) was analyzed with hierarchical cluster analysis and correlated with the underlying etiology. RESULTS: Acute vestibular neuropathy (AVN) (37.4%, 113 of 302), vestibular schwannoma (18.2%, 55 of 302), and acute cochleovestibular neuropathy (6.6%, 20 of 302) were most frequent. Horizontal SCC impairment (87.4%, 264 of 302) was more frequent (p < 0.001) than posterior (47.4%, 143 of 302) and anterior (37.8%, 114 of 302) SCC impairment. Utricular damage (58%, 175 of 302) was noted more often (p = 0.003) than saccular impairment (32%, 98 of 302). On average, 2.6 (95% confidence interval 2.48-2.78) vestibular sensors were deficient, with higher numbers (p ≤ 0.017) for acute cochleovestibular neuropathy and vestibular schwannoma than for AVN, Menière disease, and episodic vestibular syndrome. In hierarchical cluster analysis, early mergers (posterior SCC/sacculus; anterior SCC/utriculus) pointed to closer pathophysiologic association of these sensors, whereas the late merger of the horizontal canal indicated a more distinct state. CONCLUSIONS: While the extent and pattern of vestibular impairment critically depended on the underlying disorder, more limited damage in AVN and Menière disease was noted, emphasizing the individual range of loss of function and the value of vestibular mapping. Likely, both the anatomic properties of the different vestibular end organs and their vulnerability to external factors contribute to the relative sparing of the vertical canals and the sacculus.

Exergaming With Integrated Head Turn Tasks Improves Compensatory Saccade Pattern in Some Patients With Chronic Peripheral Unilateral Vestibular Hypofunction.

Background: This study aimed to determine whether vestibular rehabilitation using active video games (Exergames), including promoted head turns and unsupported locomotion, may facilitate vestibular compensation and gait in subjects with one-sided chronic peripheral vestibular hypofunction (cPVH). Methods: 12 patients with cPVH (mean age of 65 ± 12 years, 8 male) were recruited for this study. The study consisted of a four-week baseline control period T1-T2 followed by a four-week intervention period T2-T3. The intervention included exergames that required physical tasks such as steps, weight shifts or balance control to cognitive challenges, in a virtual environment to play the game. The subjects participated in a total of 176 min of exergaming in eight sessions. Because of the changing projection direction of the game to the wall, the subjects had to turn their heads constantly while playing the game. Dynamic visual acuity (DVA) was assessed. Vestibulo-Ocular reflex (VOR) gain deficit and cumulative overt saccade amplitude (COSA) were measured with the video head-impulse test. Additionally, the functional gait assessment (FGA), Extended Timed Get-Up-and-Go (ETGUG), and the Dizziness handicap inventory (DHI), were assessed. Results: DVA showed no significant group level change (p = 0.475, z = -0.714, d = 0.295) with a small effect size and improvements in five out of 12 subjects. Ipsilesional VOR gain did not improve (p = 0.157, z = -1.414, d = 0.481) on group level while there was an intermediate effect size and improvements in six out of 12 subjects. COSA got significant smaller (p = 0.006, z = -2.746, d = 1.354) with improvements in seven out of 12 subjects. The contralesional sides did not change. The FGA for the group significantly improved with an intermediate effect size (p < 0.001, z = -3.08, d = 1.617) and five individuals showed clinically relevant improvements. The ETGUG group value improved significantly with a strong effect size (p < 0.001, z = -2.67, d = 1.030), with seven individuals contributing to this change. The DHI showed no change (p = 0.172, z = -1.381, d = 0.592) neither on the group nor on the individuals' level. The game scores of the subjects improved during the intervention period of the intervention for every game. Conclusion: The results of this study demonstrate that exergaming with promoted head turns facilitates vestibular compensation in some subjects with cPVH. This is the first study that shows an improvement in cumulative overt saccade amplitude after exergaming in chronic vestibular subjects.

Repetitive ocular vestibular evoked myogenic potentials in myasthenia gravis.

OBJECTIVE: To validate the repetitive ocular vestibular evoked myogenic potentials (RoVEMP) test for diagnostic use in myasthenia gravis (MG) and to investigate its value in diagnostically challenging subgroups. METHODS: The RoVEMP test was performed in 92 patients with MG, 22 healthy controls, 33 patients with a neuromuscular disease other than MG (neuromuscular controls), 4 patients with Lambert-Eaton myasthenic syndrome, and 2 patients with congenital myasthenic syndrome. RESULTS: Mean decrement was significantly higher in patients with MG (28.4% ± 32.2) than in healthy controls (3.2% ± 13.9; p < 0.001) or neuromuscular controls (3.8% ± 26.9; p < 0.001). With neuromuscular controls as reference, a cutoff of ≥14.3% resulted in a sensitivity of 67% and a specificity of 82%. The sensitivity of the RoVEMP test was 80% in ocular MG and 63% in generalized MG. The RoVEMP test was positive in 6 of 7 patients with seronegative MG (SNMG) with isolated ocular weakness. Of 10 patients with SNMG with negative repetitive nerve stimulation (RNS) results, 73% had an abnormal RoVEMP test. The magnitude of decrement was correlated with the time since the last intake of pyridostigmine (B = 5.40; p = 0.019). CONCLUSIONS: The RoVEMP test is a new neurophysiologic test that, in contrast to RNS and single-fiber EMG, is able to measure neuromuscular transmission of extraocular muscles, which are the most affected muscles in MG. Especially in diagnostically challenging patients with negative antibody tests, negative RNS results, and isolated ocular muscle weakness, the RoVEMP test has a clear added value in supporting the diagnosis of MG. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that RoVEMP distinguishes MG from other neuromuscular diseases.

Depression in myasthenia gravis: a heterogeneous and intriguing entity.

BACKGROUND: Depressive symptoms in myasthenia gravis (MG) are common, may mimic other disease features, and contribute to misdiagnosis and diagnostic delay. Nevertheless, the clinical determinants of depressive symptoms in MG remain poorly studied, in particular their overlap with fatigue. Moreover, studies in MG have rarely looked at distinct depression phenotypes. METHODS: In 68 consecutive MG patients, we ascertained cognitive-affective and somatic depression with the Beck Depression Inventory (BDI), and also assessed age at disease onset, education, marital state, work ability, sleepiness, fatigue, and treatment modalities. Disease severity was graded according to the Myasthenia Gravis Foundation of America (MGFA) classification. RESULTS: The prevalence of moderate-severe depression was 20.5%. While depression and fatigue showed large overlap (n = 37, 54.4%), only fatigue increased with disease severity, while BDI scores did not. Thymectomy was independently associated with lower BDI scores, but had no impact on fatigue. Total BDI scores were similar in patients with predominantly cognitive-affective and with predominantly somatic depression. However, ESS correlated only with cognitive-affective BDI, and younger age was independently associated with cognitive-affective BDI. Conversely, female sex and thymectomy were independently associated with somatic BDI. CONCLUSIONS: Depression and fatigue are highly prevalent and largely overlapping comorbidities in MG, but only fatigue increased with disease severity, and only depression was milder in thymectomized patients. Comparative use of BDI subscales in MG reveals distinct depression phenotypes with distinct correlations to other disease features.

The eyes wake up: Screening for benign paroxysmal positional vertigo with polysomnography.

OBJECTIVE: While positional nystagmus of benign paroxysmal positional vertigo (BPPV) has been shown to be detectable in electrooculography (EOG) tracings of polysomnography (PSG), the frequency of undiagnosed BPPV in patients referred for sleep-wake examination has never been investigated. METHODS: Prospective evaluation of positional nystagmus in 129 patients, referred to a neurological sleep laboratory for sleep-wake examination with PSG. Both in the evening and morning, patients had diagnostic positioning maneuvers under ongoing EOG-PSG registration, followed by visual inspection of EOG for positional nystagmus. RESULTS: In 19 patients (14.7%), we found patterns of positional nystagmus, typically appearing few seconds after changes in head position. In 9 of these patients (47%), the nystagmus was also provoked by the positioning maneuvers. Nystagmus only occurred during wakefulness, not during sleep. In a patient with severe cupulolithiasis, we observed disappearance of nystagmus while entering N1 sleep stage. Nocturnal positional nystagmus was independently associated with positive positioning maneuvers. CONCLUSIONS: Inspection of EOG-PSG demonstrated that positional nystagmus is common, occurring only when wake, and independently associated with positive positioning maneuvers. SIGNIFICANCE: By routinely searching for positional nystagmus in PSG, sleep physicians may substantially contribute to the identification of patients with so-far undiagnosed BPPV.

Distinct Vestibular Evoked Myogenic Potentials in Patients With Parkinson Disease and Progressive Supranuclear Palsy.

Background: Early brainstem neurodegeneration is common in Parkinson's disease (PD) and progressive supranuclear palsy (PSP). While previous work showed abnormalities in vestibular evoked myogenic potentials (VEMPs) in patients with either disorder as compared to healthy humans, it remains unclear whether ocular and cervical VEMPs differ between PD and PSP patients. Methods: We prospectively included 12 PD and 11 PSP patients, performed ocular and cervical VEMPs, and calculated specific VEMP scores (0 = normal, 12 = most pathological) based on latencies, amplitude, and absent responses. In addition, we assessed disease duration, presence of imbalance, motor asymmetry, and motor disability using the Movement Disorder Society Unified Parkinson's Disease Rating Scale, part III (MDS-UPDRS III). Moreover, we ascertained various sleep parameters by video-polysomnography. Results: PSP and PD patients had similar oVEMP scores (6 [3-6] vs. 3 [1.3-6], p = 0.06), but PSP patients had higher cVEMP scores (3 [0-6] vs. 0 [0-2.8], p = 0.03) and total VEMP scores (9 [5-12] vs. 4 [2-7.5], p = 0.01). Moreover, total VEMP scores >10 were only observed in PSP patients (45%, p = 0.01). MDS-UPDRS III correlated with cVEMP scores (rho = 0.77, p = 0.01) in PSP, but not in PD. In PD, but not in PSP, polysomnographic markers of disturbed sleep, including decreased rapid eye movement sleep, showed significant correlations with VEMP scores. Conclusions: Our findings suggest that central vestibular pathways are more severely damaged in PSP than in PD, as indicated by higher cervical and total VEMP scores in PSP than PD in a between-groups analysis. Meaningful correlations between VEMPs and motor and non-motor symptoms further encourage its use in neurodegenerative Parkinsonian syndromes.

Repetitive ocular vestibular evoked myogenic potential stimulation for the diagnosis of myasthenia gravis: Optimization of stimulation parameters.

OBJECTIVE: To determine the most effective stimulation parameters for the diagnosis of ocular myasthenia gravis (MG) using repetitive ocular vestibular evoked myogenic potentials (oVEMP) for quantification of the extraocular muscle response decrement. METHODS: Repetitive bone-conducted oVEMPs were elicited in 18 MG patients and 20 healthy subjects. We compared four different stimulus repetition rates (20 Hz, 30 Hz, 40 Hz, 50 Hz) and 100 Hz continuous stimulation, as well as recordings from the inferior oblique muscles and the lateral rectus muscles to determine the most sensitive and specific oVEMP parameters for decrement detection. RESULTS: Repetitive stimulation at all tested repetition rates with recordings from inferior oblique muscles allowed for effective differentiation between MG patients and healthy subjects. Among all repetition rates, 30 Hz showed a trend towards superiority, with a sensitivity of 71% and a specificity of 94% (area under the curve (AUC) 0.88) when using the smaller decrement of the two eyes and -10% as cutoff. Considering the larger decrement for analysis (-9% as cutoff), sensitivity increased to 82%, but specificity decreased to 78% (AUC 0.81). CONCLUSIONS: Our study demonstrates, that repetitive oVEMP stimulation elicits a robust decrement in the inferior oblique muscles of MG patients at repetition rates between 20 Hz and 50 Hz, with a probable optimum at 30 Hz. SIGNIFICANCE: Repetitive inferior oblique oVEMP stimulation with optimal stimulus parameters facilitates early and accurate diagnosis of ocular MG.

Sound-evoked vestibular projections to the splenius capitis in humans: comparison with the sternocleidomastoid muscle.

The short-latency vestibulo-collic reflex in humans is well defined for only the sternocleidomastoid (SCM) neck muscle. However, other neck muscles also receive input from the balance organs and participate in neck stabilization. We therefore investigated the sound-evoked vestibular projection to the splenius capitis (SC) muscles by comparing surface and single motor unit responses in the SC and SCM muscles in 10 normal volunteers. We also recorded surface responses in patients with unilateral vestibular loss but preserved hearing and hearing loss but preserved vestibular function. The single motor unit responses were predominantly inhibitory, and the strongest responses were recorded in the contralateral SC and ipsilateral SCM. In both cases there was a significant decrease or gap in single motor unit activity, in SC at 11.7 ms for 46/66 units and in SCM at 12.7 ms for 51/58 motor units. There were fewer significant responses in the ipsilateral SC and contralateral SCM muscles, and they consisted primarily of weak increases in activity. Surface responses recorded over the contralateral SC were positive-negative during neck rotation, similar to the ipsilateral cervical vestibular evoked myogenic potential in SCM. Responses in SC were present in the patients with hearing loss and absent in the patient with vestibular loss, confirming their vestibular origin. The results describe a pattern of inhibition consistent with the synergistic relationship between these muscles for axial head rotation, with the crossed vestibular projection to the contralateral SC being weaker than the ipsilateral projection to the SCM. NEW & NOTEWORTHY We used acoustic vestibular stimulation to investigate the saccular projections to the splenius capitis (SC) and sternocleidomastoid (SCM) muscles in humans. Single motor unit recordings from within the muscles demonstrated strong inhibitory projections to the contralateral SC and ipsilateral SCM muscles and weak excitatory projections to the opposite muscle pair. This synergistic pattern of activation is consistent with a role for the reflex in axial rotation of the head.