Effect of prednisolone for the treatment of medication-overuse headache: A 3-month result from a multicenter REgistry for Load and management of mEdicAtion overuSE headache (RELEASE) study.

OBJECTIVE: To evaluate the efficacy of prednisolone in the treatment of medication-overuse headache (MOH) using data from a multicenter prospective registry (Registry for Load and Management of Medication Overuse Headache [RELEASE]). BACKGROUND: The treatment of MOH is challenging, especially when withdrawal headache manifests during the cessation of overused medication. Although systemic corticosteroids have been empirically used to reduce withdrawal headaches, their efficacy on the long-term outcomes of MOH has not been documented. METHODS: This was a post hoc analysis of the RELEASE study. The RELEASE is an ongoing multicenter observational cohort study in which patients with MOH have been recruited from seven hospitals in Korea since April 2020. Clinical characteristics, disease profiles, treatments, and outcomes were assessed at baseline and specific time points. We analyzed the effect of prednisolone on MOH reversal at 3 months. RESULTS: Among the 309 patients enrolled during the study period, prednisolone was prescribed to 59/309 (19.1%) patients at a dose ranging from 10 to 40 mg/day for 5-14 days; 228/309 patients (73.8%) completed the 3-month follow-up period. The MOH reversal rates at 3 months after baseline were 76% (31/41) in the prednisolone group and 57.8% (108/187) in the non-prednisolone group (p = 0.034). The effect of steroids remained significant (adjusted odds ratio 2.78, 95% confidence interval 1.27-6.1, p = 0.010) after adjusting for the number of monthly headache days at baseline, mode of discontinuation of overused medication, use of early preventive medications, and the number of preventive medications combined. CONCLUSIONS: Although our observational study could not draw a definitive conclusion, prednisolone may be effective in the treatment of MOH.

A Case Report of Acute Bilateral Mydriasis Induced by Herbal Medication.

Ma Huang (Ephedra), a traditional herbal remedy, which contains pseudoephedrine and ephedrine, has sympathomimetic characteristics. Despite being banned by the Federal Drug Administration in 2004, it is still used for weight loss and energy boosting in some countries. A previous healthy 42-year-old woman experienced sudden blurred vision in both eyes. Her pupils were dilated to 6 mm each, showing diminished light reflex responses, and were not responsive to both 0.1% and 1% pilocarpine. The day before the onset of her symptoms she had taken a herbal supplement. The woman's herbal medicine was believed to contain ephedrine, a component found in Ma Huang. The sympathomimetic effects of this substance could potentially induce mydriasis. After discontinuing the medication, her symptoms improved over 4 days, leading to a suspicion of drug-induced bilateral mydriasis. Herbal products prescribed for weight loss, which may contain potential elements such as Ma Huang, could lead to unforeseen side effects like bilateral mydriasis, and should be appropriately highlighted.

Interim analysis of the Registry for Load and Management of Medication Overuse Headache (RELEASE): A multicenter, comprehensive medication overuse headache registry.

BACKGROUND: Characteristics, disabilities, and optimal management of medication overuse headache remain uncertain. This study aimed to elucidate the clinical characteristics of patients with medication overuse headache enrolled in a medication overuse headache registry in Korea. METHODS: The Registry for Load and Management of MEdicAtion OveruSE Headache (RELEASE), a cross-sectional prospective observational study including seven referral headache centers in Korea, started enrolling adult patients with medication overuse headache in April 2020. Data included information on headache characteristics, burden on daily function, depression, anxiety, history of acute and preventive medications, and treatment strategies. RESULTS: A total of 229 patients (85.6% females; mean age, 45.5 ± 13.5 years) were enrolled by June 2021. The average durations of chronic headaches and medication overuse were 6.5 and 4.3 years, respectively. In the past month before enrollment, patients had headaches for 25 days and severe headaches for 12 days, and used acute medications for 20 days. Patients were disabled in 66.8 days in the past 3 months and had moderate/severe depression and anxiety in 56% and 35%, respectively. The proportion of patients on preventive treatments increased from 38% to 93% during the study period. CONCLUSIONS: RELEASE study reflects the current management status and opportunities to improve the quality of care in patients with medication overuse headache.

Clinical characteristics of medication-overuse headache according to the class of acute medication: A cross-sectional multicenter study.

OBJECTIVE: To characterize the clinical features of patients with medication-overuse headache (MOH) according to the class of acute medications being overused. BACKGROUND: MOH is a common global health problem, severely disabling the majority of the patients affected. Although various medications can cause MOH, whether clinical features differ according to the overused medication type remains unclear. METHODS: We analyzed data from a multicenter cross-sectional study in neurology clinics in Korea from April 2020 to June 2021. RESULTS: Among 229 eligible patients, MOH was documented in patients who overused multiple drug classes (69/229, 30.1%; most frequent occurrence), triptans (50/229, 21.8%), non-opioid analgesics (48/229, 21.0%), and combination-analgesics (40/229, 17.4%). Patients who overused multiple drug classes reported more frequent use of acute medications (median [25th-75th percentiles]: 25.0 [15.0-30.0] vs. 17.5 [10.0-25.5] days/month, p = 0.029) and fewer crystal-clear days (0.0 [0.0-9.5] vs. 9.0 [0.0-10.0] days/month, p = 0.048) than those who overused triptans. Patients who overused multiple drug classes also reported shorter intervals from chronic daily headache to the onset of MOH than patients who overused combination-analgesics (0.6 [0.2-1.9] vs. 2.4 [0.7-5.4] years, p = 0.001) or non-opioid analgesics (1.5 [0.6-4.3] years, p = 0.004). Patients who overused multiple drug classes reported more emergency room visits (1.0 [0.0-1.0] visits/year) than those who overused combination-analgesics (0.0 [0.0-1.0], p = 0.024) or non-opioid analgesics (0.0 [0.0-1.0], p = 0.030). Patients who overused triptans reported fewer headache days (21.0 [20.0-30.0] vs. 30.0 [20.5-30.0] days/month, p = 0.008) and fewer severe headache days (7.0 [4.0-10.0] vs. 10.0 [5.0-15.0] days/month, p = 0.017) than those who overused non-opioid analgesics. CONCLUSIONS: Some clinical characteristics of MOH significantly differed according to the class of overused medications. The findings from this study may contribute to the understanding of the clinical characteristics and pathophysiology of MOH.

Comparison of clinical and biological differences between patent foramen ovale subtypes in ischemic stroke.

BACKGROUNDS: The patent foramen ovale (PFO) is an atrial septal tunnel with a flap-like opening, causing a right-to-left shunt (RLS) between the atrial chambers. There are few studies on ischemic stroke characteristics based on PFO subtypes. In this study, we investigated whether there are differences in clinical characteristics, RLS amount, and the etiology of stroke defined by the Trial of ORG 10,172 in Acute Stroke Treatment (TOAST) classification between PFO subtypes. METHODS: We retrospectively analyzed consecutive ischemic stroke patients with PFO who were admitted to the Jeonbuk National University Hospital from November 2013 to February 2015, and performed a microbubble test to detect RLS. The patients were divided into two groups according to RLS characteristics: constant RLS group and provoked RLS group. We compared the clinical characteristics and degree of RLS between the PFO subtypes. RESULTS: Out of 144 ischemic patients evaluated in this study, 83 (58%) were classified into the constant RLS group and 61 (42%) into the provoked RLS group. The proportion of microembolic signal (MES) grades 3 and 4 was significantly higher in the constant RLS group than in the provoked RLS group. There were no statistical differences in the distribution of TOAST classification between the two groups. CONCLUSION: The constant RLS group showed a higher proportion of high-grade MES than the provoked RLS group.

Clinical characteristics and otolith dysfunction in presbyvestibulopathy: A retrospective cross-sectional analysis.

Objective: The Bárány Society recently established diagnostic criteria for presbyvestibulopathy, an age-related bilateral vestibular impairments in older individuals. Drawing upon a cross-sectional database, this study delves into the demographic and clinical features of presbyvestibulopathy patients and investigates the implications of otolith dysfunction. Methods: The study retrospectively analyzed 1218 patients aged 60 years or older who visited the tertiary dizziness clinic in 2020, due to symptoms of dizziness or instability. By reviewing medical records, we gathered clinical information and laboratory vestibular test results, such as cervical and ocular vestibular evoked myogenic potentials, and subjective visual vertical. Results: Out of 1218 patients aged 60 and above who reported dizziness or unsteadiness, 33 patients (2.7 %, with an average age of 74.2 ± 9.2 years) were diagnosed with presbyvestibulopathy. Deficiencies in horizontal angular vestibulo-ocular reflex were found in caloric tests (75 %), video head impulse tests (51.7 %), and rotatory chair tests (47.8 %), respectively. Otolith dysfunction was also observed, as shown by abnormal ocular and cervical vestibular evoked myogenic potentials in 62.96 % and 51.85 % of patients, and abnormal subjective visual vertical in 45.8 % of the cases. Conclusions: Among elderly patients experiencing consistent dizziness or instability, the incidence of presbyvestibulopathy was approximately 2.7 % over one year. Alongside the abnormalities detected in the horizontal angular vestibulo-ocular reflex, significant changes were also noted in the ocular and cervical vestibular evoked myogenic potentials, as well as in the subjective visual vertical tests. As a result, it's vital to underscore the significance of both otolithic function and vestibulo-ocular reflex in the fundamental mechanisms of presbyvestibulopathy.

Optimal Design of Galvanic Vestibular Stimulation for Patients with Vestibulopathy and Cerebellar Disorders.

OBJECTIVES: Galvanic vestibular stimulation (GVS) has shown positive outcomes in various neurological and psychiatric disorders, such as enhancing postural balance and cognitive functions. In order to expedite the practical application of GVS in clinical settings, our objective was to determine the best GVS parameters for patients with vestibulopathy and cerebellar disorders using optimal design calculation. METHODS: A total of 31 patients (26 males, mean age 57.03 ± 14.75 years, age range 22-82 years) with either unilateral or bilateral vestibulopathy (n = 18) or cerebellar ataxia (n = 13) were enrolled in the study. The GVS intervention included three parameters, waveform (sinusoidal, direct current [DC], and noisy), amplitude (0.4, 0.8, and 1.2 mA), and duration of stimulation (5 and 30 min), resulting in a total of 18 GVS intervention modes as input variables. To evaluate the effectiveness of GVS, clinical vertigo and gait assessments were conducted using the Dizziness Visual Analogue Scale (D-VAS), Activities-specific Balance Confidence Scale (ABC), and Scale for Assessment and Rating of Ataxia (SARA) as output variables. Optimal design and local sensitivity analysis were employed to determine the most optimal GVS modes. RESULTS: Patients with unilateral vestibulopathy experienced the most favorable results with either noisy or sinusoidal GVS at 0.4 mA amplitude for 30 min, followed by DC GVS at 0.8 mA amplitude for 5 min. Noisy GVS at 0.8 or 0.4 mA amplitude for 30 min demonstrated the most beneficial effects in patients with bilateral vestibulopathy. For patients with cerebellar ataxia, the optimal choices were noisy GVS with 0.8 or 0.4 mA amplitude for 5 or 30 min. CONCLUSIONS: This study is the first to utilize design optimization methods to identify the GVS stimulation parameters that are tailored to individual-specific characteristics of dizziness and imbalance. A sensitivity analysis was carried out along with the optimal design to offset the constraints of a limited sample size, resulting in the identification of the most efficient GVS modes for patients suffering from vestibular and cerebellar disorders.

Oculomotor fatigability with decrements of saccade and smooth pursuit for diagnosis of myasthenia gravis.

BACKGROUND AND OBJECTIVES: As the efficacy of current diagnostic methods for myasthenia gravis (MG) remains suboptimal, there is ongoing interest in developing more effective diagnostic models. As oculomotor fatigability is one of the most common and diagnostic symptoms in MG, we aimed to investigate whether quantitative saccadic and smooth-pursuit fatigability analyses with video-oculography (VOG) are useful for diagnosis of MG. METHODS: A convenience cohort of 46 MG patients was recruited prospectively, including 35 with ocular and 11 with generalized MG (mean age, 50.9 ± 14.5 years; 17 females); 24 healthy controls (HCs) (mean age, 50.6 ± 16.3 years; 13 females) also were enrolled. Seventy-five repetitive saccades and smooth pursuits were recorded in ranges of 20° (horizontal plane) and 15° (vertical plane) using a three-dimensional VOG system. Based on the oculomotor range of the second saccade and smooth pursuit and the mean ranges of the last five of each, the estimated decrements (%) reflecting oculomotor fatigability were calculated. RESULTS: The baseline oculomotor ranges did not show significant difference between the MG and HCs groups. However, following repetitive saccades and pursuits, the oculomotor ranges were decreased substantially during the last five cycles compared to baseline in the MG group. No such decrements were observed in the HC group (p < 0.01, Mann-Whitney U test). Receiver operating characteristic (ROC) analysis revealed that repetitive vertical saccades yielded the best differentiation between the MG and HC groups, with a sensitivity of 78.3% and specificity of 95.8% when using a decrement with an amplitude of 6.4% as the cutoff. CONCLUSION: This study presents an objective and reproducible method for measuring decrements of oculomotor ranges after repetitive saccadic and pursuit movements. Quantification of oculomotor fatigability using VOG could be a sensitive and specific diagnostic tool for MG and allows easy, cost-effective, accurate, and non-invasive measurements. CLASSIFICATION OF EVIDENCE: This study provides class III evidence that VOG-based quantification of saccadic and pursuit fatigability accurately identifies patients with MG.

Visuospatial cognition in acute unilateral peripheral vestibulopathy.

Background: This study aims to investigate the presence of spatial cognitive impairments in patients with acute unilateral peripheral vestibulopathy (vestibular neuritis, AUPV) during both the acute phase and the recovery phase. Methods: A total of 72 AUPV patients (37 with right-sided AUPV and 35 with left-sided AUPV; aged 34-80 years, median 60.5; 39 males, 54.2%) and 35 healthy controls (HCs; aged 43-75 years, median 59; 20 males, 57.1%) participated in the study. Patients underwent comprehensive neurotological assessments, including video-oculography, video head impulse and caloric tests, ocular and cervical vestibular-evoked myogenic potentials, and pure-tone audiometry. Additionally, the Visual Object and Space Perception (VOSP) battery was used to evaluate visuospatial perception, while the Block design test and Corsi block-tapping test assessed visuospatial memory within the first 2 days (acute phase) and 4 weeks after symptom onset (recovery phase). Results: Although AUPV patients were able to successfully perform visuospatial perception tasks within normal parameters, they demonstrated statistically worse performance on the visuospatial memory tests compared to HCs during the acute phase. When comparing right versus left AUPV groups, significant decreased scores in visuospatial perception and memory were observed in the right AUPV group relative to the left AUPV group. In the recovery phase, patients showed substantial improvements even in these previously diminished visuospatial cognitive performances. Conclusion: AUPV patients showed different spatial cognition responses, like spatial memory, depending on the affected ear, improving with vestibular compensation over time. We advocate both objective and subjective visuospatial assessments and the development of tests to detect potential cognitive deficits after unilateral vestibular impairments.

Thresholds for vestibular and cutaneous perception and oculomotor response induced by galvanic vestibular stimulation.

Objectives: In this study, the specific threshold intensities and response characteristics of galvanic vestibular stimulation (GVS) on vestibular (conscious) and cutaneous (detrimental) perception as well as oculomotor nystagmus (reflex) were determined. Methods: The threshold intensities for vestibular and cutaneous perception and oculomotor response induced by GVS were determined in 25 right-handed healthy subjects (32.6 ± 7.2 years of age; 56% female). The subjects were seated upright, and eye movements were recorded while a direct GVS current was applied with paradigms of cathode on the right and anode on the left (CRAL) and also cathode on the left and anode on the right (CLAR). Results: Subjects experienced dizziness, sense of spinning, or fall tendency, which was more frequently directed to the cathode (76%) than the anode (24%, p < 0.001, chi-square one-variable test) at mean current greater than 0.98 ± 0.29 mA (mean vestibular threshold). The current also triggered a more frequent mild tingling sensation at the cathode (56%) than the anode (30%) or on both sides (14%; p = 0.001, chi-square one-variable test) when above the mean cutaneous threshold of 0.9 ± 0.29 mA. Above the mean oculomotor threshold of 1.61 ± 0.35 mA, combined horizontal and torsional nystagmus was more frequent toward the cathode (86%) than toward the anode (p < 0.001, chi-square one-variable test). The mean oculomotor threshold was significantly higher than both the vestibular (p < 0.001, Mann-Whitney U-test) and cutaneous (p < 0.001, Mann-Whitney U-test) thresholds, which were comparable (p = 0.317, Mann-Whitney U-test). There was no significant disparity in these specific thresholds between the two GVS paradigms. The vestibular threshold was significantly higher in males than in females [1 (0.5-1.25) mA vs. 0.75 (0.625-1.125) mA, Z = -2.241, p = 0.025, Mann-Whitney U-test]. However, the thresholds of cutaneous perception and oculomotor response did not differ by sex. Conclusion: The findings indicate that thresholds for vestibular and somatosensory perception are lower than the oculomotor threshold. Therefore, a strategy to reduce GVS current intensity to the level of vestibular or somatosensory perception threshold could elicit beneficial vestibular effects while avoiding undesirable effects such as oculomotor consequences.

A preliminary trial of botulinum toxin type A in patients with vestibular migraine: A longitudinal fMRI study.

Objective: This study aims to investigate the efficacy of botulinum toxin type A (BTX-A) in the prophylactic management of vestibular migraine (VM) and to determine whether this treatment modulates intrinsic functional brain network. Methods: Vestibular migraine patients (n = 20, mean age 45.4 years) who were resistant to conventional prophylactic therapies had BTX-A injection and rs-fMRI before and 2 months after the injection. We also measured the changes in the frequency of vertigo and migraine attacks, symptomatic functional disability scores, and neuropsychiatric inventories. Results: After BTX-A injection, the mean monthly frequencies of migraine and vertigo episodes decreased significantly compared with the baseline (p < 0.01, paired t-test). The Headache Impact Test-6 score and the Migraine Disability Assessment, and the vertigo parameters, measured by the Dizziness Handicap Inventory and the Vertigo Symptom Scale, showed an improvement, as did the anxiety and depression scores 2 months after BTX-A treatment. The low-frequency fluctuation analysis of the rs-fMRI data found significant changes in the functional connectivity of the right superior temporal gyrus. Adoption of this cluster as the seed region increased the functional connectivity with the left post-central gyrus, right supramarginal gyrus, and right middle temporal gyrus after BTX-A treatment. Conclusion: This prospective study suggests that BTX-A treatment is effective at ameliorating migraine and vertigo symptoms in VM patients who were resistant to conventional therapies. Along with symptomatic improvements, changes in the functional connectivity within the multisensory vestibular and pain networks suggest a dysmodulation of multimodal sensory integration and abnormal cortical processing of the vestibular and pain signals in VM patients.

Case report: Bilateral posterior ischemic optic neuropathy in a patient with atrial fibrillation and multifocal embolic stroke.

An 80-year-old female with a history of diabetes mellitus (DM) and hypertension presented with sudden onset of sequential bilateral visual loss. The best visual acuity was light perception in the right eye and finger counting in the left eye, however, bilateral fundus did not reveal optic disc edema. Diffusion-weighted magnetic resonance imaging (MRI) of the brain revealed acute embolic stroke and diffusion restriction in the posterior portion of both optic nerves. The 24-h Holter monitor showed persistent atrial fibrillation (AF) with rapid ventricular response. The presence of painless and severe visual loss at onset unaccompanied by optic disc edema in the patient with newly detected uncontrolled AF and multiple embolic infarctions favored a diagnosis of non-arteritic posterior ischemic optic neuropathy (PION). The current case contributes to better understanding of PION pathophysiology and associated risk factors, indicating a possible relationship between non-arteritic PION and uncontrolled AF and embolic cerebral infarction.

Effects of Galvanic Vestibular Stimulation on Vestibular Compensation in Unilaterally Labyrinthectomized Mice.

Objectives: To investigate the ameliorating effects of sinusoidal galvanic vestibular stimulation (GVS) on vestibular compensation from unilateral vestibular deafferentation (UVD) using a mouse model of unilateral labyrinthectomy (UL). Methods: Sixteen male C57BL/6 mice were allocated into two groups that comprise UL groups with GVS (GVS group, n = 9) and without GVS intervention (non-GVS group, n = 7). In the experimental groups, we assessed vestibulo-ocular reflex (VOR) recovery before (baseline) and at 3, 7, and 14 days after surgical unilateral labyrinthectomy. In the GVS group, stimulation was applied for 30 min daily from postoperative days (PODs) 0-4 via electrodes inserted subcutaneously next to both bony labyrinths. Results: Locomotion and VOR were significantly impaired in the non-GVS group compared to baseline. The mean VOR gain of the non-GVS group was attenuated to 0.23 at POD 3 and recovered continuously to the value of 0.54 at POD 14, but did not reach the baseline values at any frequency. GVS intervention significantly accelerated recovery of locomotion, as assessed by the amount of circling and total path length in the open field tasks compared to the non-GVS groups on PODs 3 (p < 0.001 in both amount of circling and total path length) and 7 (p < 0.01 in amount of circling and p < 0.001 in total path length, Mann-Whitney U-test). GVS also significantly improved VOR gain compared to the non-GVS groups at PODs 3 (p < 0.001), 7 (p < 0.001), and 14 (p < 0.001, independent t-tests) during sinusoidal rotations. In addition, the recovery of the phase responses and asymmetry of the VOR was significantly better in the GVS group than in the non-GVS group until 2 weeks after UVD (phase, p = 0.001; symmetry, p < 0.001 at POD 14). Conclusion: Recoveries for UVD-induced locomotion and VOR deficits were accelerated by an early intervention with GVS, which implies that GVS has the potential to improve vestibular compensation in patients with acute unilateral vestibular failure.

Clinical Implication of Corrective Saccades in the Video Head Impulse Test for the Diagnosis of Posterior Inferior Cerebellar Artery Infarction.

Objective: In the present study, we characterized the vestibulo-ocular reflex (VOR) gain and properties of corrective saccades (CS) in patients with posterior inferior cerebellar artery (PICA) stroke and determined the best parameter to differentiate PICA stroke from benign peripheral vestibular neuritis (VN). In particular, we studied CS amplitude and asymmetry in video head impulse tests (vHITs) to discriminate these two less-studied disease conditions. Methods: The vHITs were performed within 1 week from symptom onset in patients with PICA stroke (n = 17), patients with VN (n = 17), and healthy subjects (HS, n = 17). Results: PICA stroke patients had bilaterally reduced VOR gains in the horizontal semicircular canal (HC) and the posterior semicircular canal (PC) compared with HSs. When compared with VN patients, PICA stroke patients showed preserved gains in the HC and anterior semicircular canal (AC) bilaterally (i.e., symmetric VOR gain). Similar to VOR gain, smaller but bilaterally symmetric CS in the HC and AC were observed in PICA stroke patients compared with VN patients; the mean amplitude of CS for the ipsilesional HC was reduced (p < 0.001, Mann-Whitney U-test), but the mean amplitude of CS for the contralesional HC was increased (p < 0.03, Mann-Whitney U-test) in PICA stroke compared with VN. The receiver operating characteristic (ROC) curve showed that CS amplitude asymmetry (CSs) and VOR gain asymmetry (Gs) of HC are excellent parameters to distinguish PICA stroke from VN. Conclusion: In the current study, we quantitatively investigated the VOR gain and CS using vHITs for three semicircular canals in PICA stroke and VN patients. In addition to VOR gain, quantitative assessments of CS using vHITs can provide sensitive and objective parameters to distinguish between peripheral and central vestibulopathies.

The Differential Effects of Acute Right- vs. Left-Sided Vestibular Deafferentation on Spatial Cognition in Unilateral Labyrinthectomized Mice.

This study aimed to investigate the disparity in locomotor and spatial memory deficits caused by left- or right-sided unilateral vestibular deafferentation (UVD) using a mouse model of unilateral labyrinthectomy (UL) and to examine the effects of galvanic vestibular stimulation (GVS) on the deficits over 14 days. Five experimental groups were established: the left-sided and right-sided UL (Lt.-UL and Rt.-UL) groups, left-sided and right-sided UL with bipolar GVS with the cathode on the lesion side (Lt.-GVS and Rt.-GVS) groups, and a control group with sham surgery. We assessed the locomotor and cognitive-behavioral functions using the open field (OF), Y maze, and Morris water maze (MWM) tests before (baseline) and 3, 7, and 14 days after surgical UL in each group. On postoperative day (POD) 3, locomotion and spatial working memory were more impaired in the Lt.-UL group compared with the Rt.-UL group (p < 0.01, Tamhane test). On POD 7, there was a substantial difference between the groups; the locomotion and spatial navigation of the Lt.-UL group recovered significantly more slowly compared with those of the Rt.-UL group. Although the differences in the short-term spatial cognition and motor coordination were resolved by POD 14, the long-term spatial navigation deficits assessed by the MWM were significantly worse in the Lt.-UL group compared with the Rt.-UL group. GVS intervention accelerated the vestibular compensation in both the Lt.-GVS and Rt.-GVS groups in terms of improvement of locomotion and spatial cognition. The current data imply that right- and left-sided UVD impair spatial cognition and locomotion differently and result in different compensatory patterns. Sequential bipolar GVS when the cathode (stimulating) was assigned to the lesion side accelerated recovery for UVD-induced spatial cognition, which may have implications for managing the patients with spatial cognitive impairment, especially that induced by unilateral peripheral vestibular damage on the dominant side.

Galvanic Vestibular Stimulation Improves Spatial Cognition After Unilateral Labyrinthectomy in Mice.

Objectives: To investigate the deficits of spatial memory and navigation from unilateral vestibular deafferentation (UVD) and to determine the efficacy of galvanic vestibular stimulation (GVS) for recovery from these deficits using a mouse model of unilateral labyrinthectomy (UL). Methods: Thirty-six male C57BL/6 mice were allocated into three groups that comprise a control group and two experimental groups, UVD with (GVS group) and without GVS intervention (non-GVS group). In the experimental groups, we assessed the locomotor and cognitive behavioral function before (baseline) and 3, 7, and 14 days after surgical UL, using the open field (OF), Y maze, and Morris water maze (MWM) tests. In the GVS group, the stimulations were applied for 30 min daily from postoperative day (POD) 0-4 via the electrodes inserted subcutaneously close to both bony labyrinths. Results: Locomotion and spatial cognition were significantly impaired in the mice with UVD non-GVS group compared to the control group. GVS significantly accelerated recovery of locomotion compared to the control and non-GVS groups on PODs 3 (p < 0.001) and 7 (p < 0.05, Kruskal-Wallis and Mann-Whitney U tests) in the OF and Y maze tests. The mice in the GVS group were better in spatial working memory assessed with spontaneous alternation performance and spatial reference memory assessed with place recognition during the Y maze test than those in the non-GVS group on POD 3 (p < 0.001). In addition, the recovery of long-term spatial navigation deficits during the MWM, as indicated by the escape latency and the probe trial, was significantly better in the GVS group than in the non-GVS group 2 weeks after UVD (p < 0.01). Conclusions: UVD impairs spatial memory, navigation, and motor coordination. GVS accelerated recoveries in short- and long-term spatial memory and navigation, as well as locomotor function in mice with UVD, and may be applied to the patients with acute unilateral vestibular failure.

Endolymphatic Hydrops in Patients With Vestibular Migraine and Concurrent Meniere's Disease.

Objective: Intravenous contrast agent enhanced, high-resolution magnetic resonance imaging of the inner ear (iMRI) confirmed that patients with Menière's disease (MD) and vestibular migraine (VM) could present with endolymphatic hydrops (EH). The present study aimed to investigate EH characteristics and their interrelation to neurotologic testing in patients with VM, MD, or VM with concurrent MD (VM-MD). Methods: Sixty-two patients (45 females, aged 23-81 years) with definite or probable VM (n = 25, 19 definite), MD (n = 29, 17 definite), or showing characteristics of both diseases (n = 8) were included in this study. Diagnostic workup included neurotologic assessments including video-oculography (VOG) during caloric stimulation and head-impulse test (HIT), ocular and cervical vestibular evoked myogenic potentials (o/cVEMP), pure tone audiometry (PTA), as well as iMRI. EH's degree was assessed visually and via volumetric quantification using a probabilistic atlas-based segmentation of the bony labyrinth and volumetric local thresholding (VOLT). Results: Although a relevant number of VM patients reported varying auditory symptoms (13 of 25, 52.0%), EH in VM was only observed twice. In contrast, EH in VM-MD was prevalent (2/8, 25%) and in MD frequent [23/29, 79.3%; χ2(2) = 29.1, p < 0.001, φ = 0.7]. Location and laterality of EH and neurophysiological testing classifications were highly associated (Fisher exact test, p < 0.005). In MD, visual semi-quantitative grading and volumetric quantification correlated highly to each other (r S = 0.8, p < 0.005, two-sided) and to side differences in VOG during caloric irrigation (vestibular EH ipsilateral: r S = 0.6, p < 0.05, two-sided). In VM, correlations were less pronounced. VM-MD assumed an intermediate position between VM and MD. Conclusion: Cochlear and vestibular hydrops can occur in MD and VM patients with auditory symptoms; this suggests inner ear damage irrespective of the diagnosis of MD or VM. The EH grades often correlated with auditory symptoms such as hearing impairment and tinnitus. Further research is required to uncover whether migraine is one causative factor of EH or whether EH in VM patients with auditory symptoms suggests an additional pathology due to MD.

Neural Correlates of Transient Mal de Debarquement Syndrome: Activation of Prefrontal and Deactivation of Cerebellar Networks Correlate With Neuropsychological Assessment.

Background: Mal de debarquement syndrome (MdDS) is characterized by a subjective perception of self-motion after exposure to passive motion, mostly after sea travel. A transient form of MdDS (t-MdDS) is common in healthy individuals without pathophysiological certainty. In the present cross-sectional study, the possible neuropsychiatric and functional neuroimaging changes in local fishermen with t-MdDS were evaluated. Methods: The present study included 28 fishermen from Buan County in South Korea; 15 (15/28, 53.6%) participants experienced t-MdDS for 1-6 h, and 13 were asymptomatic (13/28, 46.4%). Vestibular function tests were performed using video-oculography, the video head impulse test, and ocular and cervical vestibular-evoked myogenic potentials. Visuospatial function was also assessed by the Corsi block test. Brain imaging comprised structural MRI, resting-state functional MRI, and [18F]FDG PET scans. Results: The results of vestibular function tests did not differ between the fishermen with and those without t-MdDS. However, participants with t-MdDS showed better performance in visuospatial memory function than those without t-MdDS (6.40 vs. 5.31, p-value = 0.016) as determined by the Corsi block test. Structural brain MRIs were normal in both groups. [18F]FDG PET showed a relative hypermetabolism in the bilateral occipital and prefrontal cortices and hypometabolism in the vestibulocerebellum (nodulus and uvula) in participants with t-MdDS compared to those without t-MdDS. Resting-state functional connectivities were significantly decreased between the vestibular regions of the flocculus, superior temporal gyrus, and parietal operculum and the visual association areas of the middle occipital gyrus, fusiform gyrus, and cuneus in participants with t-MdDS. Analysis of functional connectivity of the significant regions in the PET scans revealed decreased connectivity between the prefrontal cortex and visual processing areas in the t-MdDS group. Conclusion: Increased visuospatial memory, altered metabolism in the prefrontal cortex, visual cognition cortices, and the vestibulocerebellum, and decreased functional connectivity between these two functional areas might indicate reductions in the integration of vestibular input and enhancement of visuospatial attention in subjects with t-MdDS. Current functional neuroimaging similarities from transient MdDS via chronic MdDS to functional dizziness and anxiety disorders suggest a shared mechanism of enhanced self-awareness as a kind of continuum or as overlap disorders.

Altered Resting-State Functional Connectivity in Wernicke's Encephalopathy With Vestibular Impairment.

Objectives: To reveal the neural basis of Wernicke's encephalopathy (WE) with impaired vestibulo-ocular reflex (VOR), we evaluated resting-state functional connectivity (rs-fc) in the vestibular processing brain regions. Methods: Rs-fc between the vestibular regions and the rest of the brain were compared with neurotological features including the head-impulse tests (vHIT) and caloric responses in patients with WE (n = 5, mean age 53.4 ± 10 years) and healthy controls (n = 20, mean age 55.0 ± 9.2 years). Rs-fc analyses employed a region of interest (ROI)-based approach using regions selected a priori that participate in vestibular processing including the cerebellar vermis, insula, parietal operculum, and calcarine cortex. Results: The main neurologic findings for patients with WE were mental changes; gait ataxia; spontaneous and gaze-evoked nystagmus (GEN); and bilaterally positive HIT for the horizontal canals. Video HIT documented bilateral horizontal canal dysfunction with decreased gain and corrective saccades. Caloric irrigation and rotation chair testing revealed prominent bilateral horizontal canal paresis. Patients with WE also had decreased spatial memory, which substantially recovered after treatments. Functional connections at the predefined seed regions, including the insular cortex and parietal operculum, were attenuated in the WE group compared to healthy controls. Conclusions: WE is related to impaired VOR and visuospatial dysfunction, and fMRI documented changes in the rs-fc of multisensory vestibular processing regions including the insula, parietal operculum, and superior temporal gyrus, which participate in integration of vestibular perception.