Differentiated pattern of complement system activation between MOG-IgG-associated disease and AQP4-IgG-positive neuromyelitis optica spectrum disorder.

Background: Myelin oligodendrocyte glycoprotein antibody (MOG) immunoglobulin G (IgG)-associated disease (MOGAD) has clinical and pathophysiological features that are similar to but distinct from those of aquaporin-4 antibody (AQP4-IgG)-positive neuromyelitis optica spectrum disorders (AQP4-NMOSD). MOG-IgG and AQP4-IgG, mostly of the IgG1 subtype, can both activate the complement system. Therefore, we investigated whether the levels of serum complement components, regulators, and activation products differ between MOGAD and AQP4-NMOSD, and if complement analytes can be utilized to differentiate between these diseases. Methods: The sera of patients with MOGAD (from during an attack and remission; N=19 and N=9, respectively) and AQP4-NMOSD (N=35 and N=17), and healthy controls (N=38) were analyzed for C1q-binding circulating immune complex (CIC-C1q), C1 inhibitor (C1-INH), factor H (FH), C3, iC3b, and soluble terminal complement complex (sC5b-9). Results: In attack samples, the levels of C1-INH, FH, and iC3b were higher in the MOGAD group than in the NMOSD group (all, p<0.001), while the level of sC5b-9 was increased only in the NMOSD group. In MOGAD, there were no differences in the concentrations of complement analytes based on disease status. However, within AQP4-NMOSD, remission samples indicated a higher C1-INH level than attack samples (p=0.003). Notably, AQP4-NMOSD patients on medications during attack showed lower levels of iC3b (p<0.001) and higher levels of C3 (p=0.008), C1-INH (p=0.004), and sC5b-9 (p<0.001) compared to those not on medication. Among patients not on medication at the time of attack sampling, serum MOG-IgG cell-based assay (CBA) score had a positive correlation with iC3b and C1-INH levels (rho=0.764 and p=0.010, and rho=0.629 and p=0.049, respectively), and AQP4-IgG CBA score had a positive correlation with C1-INH level (rho=0.836, p=0.003). Conclusions: This study indicates a higher prominence of complement pathway activation and subsequent C3 degradation in MOGAD compared to AQP4-NMOSD. On the other hand, the production of terminal complement complexes (TCC) was found to be more substantial in AQP4-NMOSD than in MOGAD. These findings suggest a strong regulation of the complement system, implying its potential involvement in the pathogenesis of MOGAD through mechanisms that extend beyond TCC formation.

Clinical characteristics of persistent postural-perceptual dizziness and its visual subtype in Korean patients: A multicenter cross-sectional study.

OBJECTIVES: Persistent postural-perceptual dizziness (PPPD) is a chronic functional vestibular disorder for which the Bárány Society has established diagnostic criteria. This nationwide multicenter study aims to investigate the clinical features of individuals with definite PPPD and clinical variant PPPD who do not fully meet the diagnostic criteria, with a particular focus on visual exaggeration. METHODS: Between September 2020 and September 2021, a total of 76 individuals with definite PPPD and 109 individuals with clinical variant PPPD who did not meet all three exacerbating factors outlined in Criterion B were recruited from 18 medical centers in South Korea. The study gathered information on demographic factors, clinical manifestations, balance scales, and personality assessments. RESULTS: Comparative analysis between groups with definite PPPD and clinical variant with visual exacerbation revealed no significant differences in sociodemographic characteristics, clinical course, dizziness impact, and specific precipitants. Only disease duration was significantly longer in definite PPPD compared with variant with visual exacerbation. However, the variant without visual exacerbation displayed significantly reduced rates of panic disorder, diminished space-motion discomfort, lesser impact of dizziness, and decreased prevalence of depression when compared with the definitive PPPD. CONCLUSION: This is the first comprehensive nationwide study examining clinical features of both definite PPPD patients and its clinical variants, considering visual exacerbating factors. Differences in dizziness and personality traits emerged between definite PPPD and its potential variant without visual issues. Our results highlight the possibility of a distinct clinical variant of PPPD influenced by visual dependency.

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.

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.

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.

Bidirectional association between Parkinson's disease and obstructive sleep apnea: a cohort study.

STUDY OBJECTIVES: Chronic intermittent hypoxia due to obstructive sleep apnea (OSA) causes oxidative stress, which may contribute to the pathophysiology of Parkinson's disease (PD). However, the bidirectional relationship between PD and OSA has not been satisfactorily established. The objective of this study was to try to estimate whether there is a bidirectional relationship between PD and OSA through a retrospective cohort study in the South Korean population. METHODS: This study used data from the Korean National Health Information Database of the National Health Insurance Service, which contains data from 3.5 million individuals evenly distributed. In study 1, patients with OSA were matched in a 1:2 ratio with non-OSA controls. In study 2, patients with PD were matched in a 1:2 ratio with non-PD controls. A stratified Cox proportional hazards model was used to calculate hazard ratios. RESULTS: In study 1, which included 6,396 patients with OSA and 12,792 non-OSA controls, the incidence of PD per 10,000 person-years was 11.59 in the OSA group and 8.46 in the non-OSA group. The OSA group demonstrated a 1.54-fold higher incidence of PD than the non-OSA group (95% confidence interval, 1.14-2.07; P < .05). In study 2, which included 3,427 patients with PD and 6,854 non-PD controls, the incidence of OSA per 10,000 person-years was 14.97 in the PD group and 7.72 in the non-PD group. The PD group demonstrated a 1.92-fold higher incidence of OSA than the non-PD group (95% confidence interval, 1.32-2.78; P < .05). CONCLUSIONS: This study supports a possible bidirectional relationship between PD and OSA. CITATION: Jeon S-H, Hwang YS, Oh S-Y, et al. Bidirectional association between Parkinson's disease and obstructive sleep apnea: a cohort study. J Clin Sleep Med. 2023;19(9):1615-1623.

A pilot study to explore the effect of udenafil on cerebral hemodynamics in older adults.

OBJECTIVE: Phosphodiesterase-5 inhibitors (PDE5Is) enhance vasodilation. We investigated the effects of PDE5I on cerebral hemodynamics during cognitive tasks using functional near-infrared spectroscopy (fNIRS). METHODS: This study used a crossover design. Twelve cognitively healthy men participants (mean age, 59 ± 3 years; range, 55-65 years) were recruited and randomly assigned to the experimental or control arm, then the experimental and control arm were exchanged after 1 week. Udenafil 100 mg was administered to participants in the experimental arm once daily for 3 days. We measured the fNIRS signal during the resting state and four cognitive tasks three times for each participant: at baseline, in the experimental arm, and in the control arm. RESULTS: Behavioral data did not show a significant difference between the experimental and control arms. The fNIRS signal showed significant decreases in the experimental arm compared to the control arm during several cognitive tests: verbal fluency test (left dorsolateral prefrontal cortex, T = -3.02, p = 0.014; left frontopolar cortex, T = -4.37, p = 0.002; right dorsolateral prefrontal cortex, T = -2.59, p = 0.027), Korean-color word Stroop test (left orbitofrontal cortex, T = -3.61, p = 0.009), and social event memory test (left dorsolateral prefrontal cortex, T = -2.35, p = 0.043; left frontopolar cortex, T = -3.35, p = 0.01). INTERPRETATION: Our results showed a paradoxical effect of udenafil on cerebral hemodynamics in older adults. This contradicts our hypothesis, but it suggests that fNIRS is sensitive to changes in cerebral hemodynamics in response to PDE5Is.

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.

Evaluation of Alisertib Alone or Combined With Fulvestrant in Patients With Endocrine-Resistant Advanced Breast Cancer: The Phase 2 TBCRC041 Randomized Clinical Trial.

Importance: Aurora A kinase (AURKA) activation, related in part to AURKA amplification and variants, is associated with downregulation of estrogen receptor (ER) α expression, endocrine resistance, and implicated in cyclin-dependent kinase 4/6 inhibitor (CDK 4/6i) resistance. Alisertib, a selective AURKA inhibitor, upregulates ERα and restores endocrine sensitivity in preclinical metastatic breast cancer (MBC) models. The safety and preliminary efficacy of alisertib was demonstrated in early-phase trials; however, its activity in CDK 4/6i-resistant MBC is unknown. Objective: To assess the effect of adding fulvestrant to alisertib on objective tumor response rates (ORRs) in endocrine-resistant MBC. Design, Setting, and Participants: This phase 2 randomized clinical trial was conducted through the Translational Breast Cancer Research Consortium, which enrolled participants from July 2017 to November 2019. Postmenopausal women with endocrine-resistant, ERBB2 (formerly HER2)-negative MBC who were previously treated with fulvestrant were eligible. Stratification factors included prior treatment with CDK 4/6i, baseline metastatic tumor ERα level measurement (<10%, ≥10%), and primary or secondary endocrine resistance. Among 114 preregistered patients, 96 (84.2%) registered and 91 (79.8%) were evaluable for the primary end point. Data analysis began after January 10, 2022. Interventions: Alisertib, 50 mg, oral, daily on days 1 to 3, 8 to 10, and 15 to 17 of a 28-day cycle (arm 1) or alisertib same dose/schedule with standard-dose fulvestrant (arm 2). Main Outcomes and Measures: Improvement in ORR in arm 2 of at least 20% greater than arm 1 when the expected ORR for arm 1 was 20%. Results: All 91 evaluable patients (mean [SD] age, 58.5 [11.3] years; 1 American Indian/Alaskan Native [1.1%], 2 Asian [2.2%], 6 Black/African American [6.6%], 5 Hispanic [5.5%], and 79 [86.8%] White individuals; arm 1, 46 [50.5%]; arm 2, 45 [49.5%]) had received prior treatment with CDK 4/6i. The ORR was 19.6%; (90% CI, 10.6%-31.7%) for arm 1 and 20.0% (90% CI, 10.9%-32.3%) for arm 2. In arm 1, the 24-week clinical benefit rate and median progression-free survival time were 41.3% (90% CI, 29.0%-54.5%) and 5.6 months (95% CI, 3.9-10.0), respectively, and in arm 2 they were 28.9% (90% CI, 18.0%-42.0%) and 5.4 months (95% CI, 3.9-7.8), respectively. The most common grade 3 or higher adverse events attributed to alisertib were neutropenia (41.8%) and anemia (13.2%). Reasons for discontinuing treatment were disease progression (arm 1, 38 [82.6%]; arm 2, 31 [68.9%]) and toxic effects or refusal (arm 1, 5 [10.9%]; arm 2, 12 [26.7%]). Conclusions and Relevance: This randomized clinical trial found that adding fulvestrant to treatment with alisertib did not increase ORR or PFS; however, promising clinical activity was observed with alisertib monotherapy among patients with endocrine-resistant and CDK 4/6i-resistant MBC. The overall safety profile was tolerable. Trial Registration: ClinicalTrials.gov Identifier: NCT02860000.

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.

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.

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.

The Effect of Galvanic Vestibular Stimulation on Visuospatial Cognition in an Incomplete Bilateral Vestibular Deafferentation Mouse Model.

Objectives: To evaluate the efficacy of galvanic vestibular stimulation (GVS) for recovering from the locomotor and spatial memory deficits of a murine bilateral vestibular deafferentation (BVD) model. Methods: Male C57BL/6 mice (n = 36) were assigned to three groups: bilateral labyrinthectomy with (BVD_GVS group) and without (BVD_non-GVS group) the GVS intervention, and a control group with the sham operation. We used the open field and Y maze, and Morris water maze (MWM) tests to assess locomotor and visuospatial cognitive performance before (baseline) and 3, 7, and 14 days after surgical bilateral labyrinthectomy. For the GVS group, a sinusoidal current at the frequency at 1 Hz and amplitude 0.1 mA was delivered for 30 min daily from the postoperative day (POD) 0 to 4 via electrodes inserted subcutaneously close to both the bony labyrinths. Results: Short-term spatial memory was significantly impaired in bilaterally labyrinthectomized mice (BVD_non-GVS group), as reflected by decreased spontaneous alternation performance in the place recognition test and time spent in the novel arm and increased same arm return in the Y-maze test, compared with the control. Long-term spatial memory was also impaired, as indicated by a longer escape latency in the hidden platform trial and a lower percentage of time spent in the target quadrant in the probe trial of the MWM. GVS application significantly accelerated the recovery of locomotion and short-term and long-term spatial memory deficits in the BVD mice. Conclusions: Our data demonstrate that locomotion, short-term, and long-term (at least 2 weeks) spatial memory were impaired in BVD mice. The early administration of sinusoidal GVS accelerated the recovery of those locomotion and spatial memory deficiencies. GVS could be applied to patients with BVD to improve their locomotion and vestibular cognitive functioning.

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.

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.