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Brain : a Journal of Neurology Jun 20244-repeat (4R) tauopathies are neurodegenerative diseases characterized by cerebral accumulation of 4R tau pathology. The most prominent 4R-tauopathies are...
4-repeat (4R) tauopathies are neurodegenerative diseases characterized by cerebral accumulation of 4R tau pathology. The most prominent 4R-tauopathies are progressive-supranuclear-palsy (PSP) and corticobasal-degeneration (CBD) characterized by subcortical tau accumulation and cortical neuronal dysfunction, as shown by PET-assessed hypoperfusion and glucose hypometabolism. Yet, there is a spatial mismatch between subcortical tau deposition patterns and cortical neuronal dysfunction, and it is unclear how these two pathological brain changes are interrelated. Here, we hypothesized that subcortical tau pathology induces remote neuronal dysfunction in functionally connected cortical regions to test a pathophysiological model that mechanistically links subcortical tau accumulation to cortical neuronal dysfunction in 4R tauopathies. We included 51 Aβ-negative patients with clinically diagnosed PSP variants (n=26) or Corticobasal Syndrome (CBS; n=25) who underwent structural MRI and 18F-PI-2620 tau-PET. 18F-PI-2620 tau-PET was recorded using a dynamic one-stop-shop acquisition protocol, to determine an early 0.5-2.5 min post-tracer-injection perfusion window for assessing cortical neuronal dysfunction, as well as a 20-40 min post-tracer-injection window to determine 4R-tau load. Perfusion-PET (i.e. early-window) was assessed in 200 cortical regions, and tau-PET was assessed in 32 subcortical regions of established functional brain atlasses. We determined tau epicenters as subcortical regions with highest 18F-PI-2620 tau-PET signal and assessed the connectivity of tau epicenters to cortical ROIs using a resting-state fMRI-based functional connectivity template derived from 69 healthy elderly controls from the ADNI cohort. Using linear regression, we assessed whether i) higher subcortical tau-PET was associated with reduced cortical perfusion and ii) whether cortical perfusion reductions were observed preferentially in regions closely connected to subcortical tau epicenters. As hypothesized, higher subcortical tau-PET was associated with overall lower cortical perfusion, which remained consistent when controlling for cortical tau-PET. Using group-average and subject-level PET data, we found that the seed-based connectivity pattern of subcortical tau epicenters aligned with cortical perfusion patterns, where cortical regions that were more closely connected to the tau epicenter showed lower perfusion. Together, subcortical tau-accumulation is associated with remote perfusion reductions indicative of neuronal dysfunction in functionally connected cortical regions in 4R-tauopathies. This suggests that subcortical tau pathology may induce cortical dysfunction, which may contribute to clinical disease manifestation and clinical heterogeneity.
PubMed: 38842726
DOI: 10.1093/brain/awae174 -
Scientific Reports Jun 2024Dizziness is one of the most prevalent complaints in medicine, and benign paroxysmal positional vertigo (BPPV) accounts for one-third of all cases. The present study was...
Dizziness is one of the most prevalent complaints in medicine, and benign paroxysmal positional vertigo (BPPV) accounts for one-third of all cases. The present study was aimed at identifying differences in the course and prognosis of BPPV depending on the patient's medical condition during hospitalization. Patients in group 1 were hospitalized due to trauma, those in group 2 for scheduled surgery, and those in group 3 for medical treatment. The intervals from admission to symptom onset, surgery to symptom onset, and symptom onset to ENT department referral were compared. The interval from admission to symptom onset was shortest in group 1 (3.1 ± 8.0 days) and differed significantly from that in group 3 (20.0 ± 35.0 days, p < 0.001). The interval from surgery to symptom onset for group 2 was 5.6 ± 5.8 days and was significantly shorter than that from admission to symptom onset for group 3 (p = 0.014). The interval from symptom onset to ENT referral in group 3 (2.0 ± 2.8 days) was significantly shorter than in groups 1 and 2 (4.1 ± 5.1 and 4.0 ± 3.6 days, p = 0.008 and p = 0.002, respectively). The findings imply that the course of BPPV differed according to the patients' medical condition.
Topics: Humans; Benign Paroxysmal Positional Vertigo; Male; Female; Middle Aged; Aged; Adult; Hospitalization; Prognosis; Dizziness; Aged, 80 and over
PubMed: 38839867
DOI: 10.1038/s41598-024-63882-3 -
Journal of Neurology Jun 2024Video head impulse tests (video-HITs) are commonly used for vestibular evaluation; however, the results can be contaminated by various artifacts, including technical...
Video head impulse tests (video-HITs) are commonly used for vestibular evaluation; however, the results can be contaminated by various artifacts, including technical errors, recording problems, and participant factors. Although video-HITs can be used in patients with Parkinson's disease (PD), the effect of neck rigidity has not been systematically investigated. This study aimed to investigate the effect of neck rigidity on video-HIT results in patients with PD. We prospectively recruited 140 consecutive patients with PD (mean age ± standard deviation = 68 ± 10 years, 69 men) between September 2021 and April 2024 at Korea University Medical Center. The video-HIT results were compared with those of 19 age- and sex-matched healthy participants. Neck rigidity was stratified as a subdomain of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale motor part (MDS-UPDRS-III). In 59 patients, the vestibulo-ocular reflex (VOR) gain was overestimated in at least one canal plane (58/140, 41%), mostly in the anterior canal (AC, n = 44), followed by the horizontal (HC, n = 15) and posterior canals (PC, n = 7). VOR gain overestimation was also observed in patients with no (18/58, 35%), subtle (20/58, 34%), or mild (17/58, 29%) neck rigidity. Multivariable logistic regression analysis showed that VOR overestimation was positively associated with neck rigidity (odds ratio [OR] [95% confidence interval] = 1.51 [1.01-2.25], p = 0.043). The head velocities of patients decreased during head impulses for the AC (p = 0.033 for the right AC; p = 0.014 for the left AC), whereas eye velocities were similar to those of healthy participants. Our findings suggest that neck rigidity may be a confounder that can contaminate video-HIT results. Thus, the results of video-HITs, especially for the AC, should be interpreted with the context of head velocity during head impulses in patients with neck rigidity.
PubMed: 38839639
DOI: 10.1007/s00415-024-12488-w -
Auris, Nasus, Larynx Jun 2024In Japan, intravenous injection of a 7 % solution of sodium bicarbonate (NaHCO) had been originally developed to inhibit motion sickness and then have long been used to...
OBJECTIVE
In Japan, intravenous injection of a 7 % solution of sodium bicarbonate (NaHCO) had been originally developed to inhibit motion sickness and then have long been used to treat vertigo. Previously, we reported that Fos-positive neurons appear in the amygdala after hypergravity stimulation in rats. In the present study, we examined whether injection of 7 % NaHCO inhibits hypergravity-induced Fos expression in the neurons in the central nucleus of the amygdala in rats.
METHODS
Rats were exposed to 2 G hypergravity in an animal centrifuge device for 3 h. A solution of 7 % NaHCO at a dose of 4 mM/kg was injected intraperitoneally before 2 G hypergraviy. Fos-positive neurons in the amygdala were stained immunohistochemically.
RESULTS
The number of Fos-positive neurons in the central nucleus of the amygdala was significantly increased after 2 G hypergravity in rats that received no drugs or saline, compared to that in rats exposed only to the noise of the centrifuge and received 7 % NaHCO solution. The number of Fos-positive neurons in the central nucleus of the amygdala after 2 G hypergravity was significantly decreased in rats that received 7 % NaHCO solution, compared to that in rats that received no drugs or saline.
CONCLUSION
Since Fos expression is a marker of activated neurons, the present findings suggest that hypergravity activates the amygdala and that administration of 7 % NaHCO suppresses hypergravity-induced activation of the amygdala. Hypergravity disturbs spatial orientation to produce motion sickness and the amygdala is involved in fear response. Recently, Ziemann et al. suggested that fear-evoking stimuli reduce the pH in the amygdala to activate it, leading to induction of fear behavior and that administering HCO attenuates fear behavior [Cell 2009; 139: 1012-1021]. Therefore, it is possible that hypergravity reduces the pH in the amygdala to activate it, thereby inducing the fear associated with motion sickness and that administration of 7 % NaHCO increases the brain pH thereby suppressing hypergravity-induced activation of the amygdala and inhibiting the fear associated with motion sickness. In patients with vertigo, 7 % NaHCO therapy may increase the brain pH thereby suppressing the activation of the amygdala and inhibiting the fear associated with vertigo to elicit a beneficial clinical effect.
PubMed: 38838426
DOI: 10.1016/j.anl.2024.05.006 -
Brazilian Journal of Otorhinolaryngology May 2024Dizziness or vertigo in older population frequently presents in clinical settings, yet its etiology remains elusive. The objective of this study was to delineate global... (Review)
Review
OBJECTIVE
Dizziness or vertigo in older population frequently presents in clinical settings, yet its etiology remains elusive. The objective of this study was to delineate global trends and identify frontiers in research concerning dizziness or vertigo among older population.
METHODS
We searched the research literature published from 2003 to 2022 on older population with dizziness or vertigo using two databases from the Web of Science Core Collection. A bibliometric and visualization analysis was conducted. Bibliometric tools facilitated co-authorship, co-citation, and keyword co-occurrence analyses, encompassing countries or regions, institutions, authors, journals, and references.
RESULTS
The analysis included 1322 publications authored by 6524 individuals from 2244 institutions across 67 countries or regions, spanning 92 subject categories. A steady increase in publications was noted from 2003 to 2022. The University of Munich, Harvard University, and the University of California System emerged as leading institutions with the highest publication outputs. The United States, Germany, and China were predominant in publication counts. Eva Grill was identified as the most prolific author. Otology & Neurotology and Geriatrics & Gerontology emerged as the most prolific journal and subject category, respectively. The most prevalent keywords were "dizziness", "vertigo", "falls", and "geriatric", with "management", "gait", and "association" recognized as the principal research hotspots.
CONCLUSION
This study provides a systematic analysis of global scientific research on older population dizziness/vertigo, revealing significant advancements in understanding over the past two decades. Management, gait, and association have emerged as the primary research focuses on recent years. These findings offer valuable insights for directing current research efforts to capture prevailing trends and explore new frontiers in this field.
PubMed: 38834014
DOI: 10.1016/j.bjorl.2024.101441 -
JMIR Formative Research Jun 2024The subjective visual vertical (SVV) test can evaluate otolith function and spatial awareness and is performed in dedicated vertigo centers using specialized equipment;...
BACKGROUND
The subjective visual vertical (SVV) test can evaluate otolith function and spatial awareness and is performed in dedicated vertigo centers using specialized equipment; however, it is not otherwise widely used because of the specific equipment and space requirements. An SVV test smartphone app was developed to easily perform assessments in outpatient facilities.
OBJECTIVE
This study aimed to verify whether the SVV test smartphone app with commercially available virtual reality goggles can be used in a clinical setting.
METHODS
The reference range was calculated for 15 healthy participants. We included 14 adult patients with unilateral vestibular neuritis, sudden sensorineural hearing loss with vertigo, and Meniere disease and investigated the correlation between the SVV test results and vestibular evoked myogenic potential (VEMP) results.
RESULTS
The SVV reference range of healthy participants for the sitting front-facing position was small, ranging from -2.6º to 2.3º. Among the 14 patients, 6 (43%) exceeded the reference range for healthy participants. The SVV of patients with vestibular neuritis and sudden sensorineural hearing loss tended to deviate to the affected side. A total of 9 (64%) had abnormal cervical VEMP (cVEMP) values and 6 (43%) had abnormal ocular VEMP (oVEMP) values. No significant difference was found between the presence or absence of abnormal SVV values and the presence or absence of abnormal cVEMP and oVEMP values; however, the odds ratios (ORs) suggested a higher likelihood of abnormal SVV values among those with abnormal cVEMP and oVEMP responses (OR 2.40, 95% CI 0.18-32.88; P>.99; and OR 2, 95% CI 0.90-4.45; P=.46, respectively).
CONCLUSIONS
The SVV app can be used anywhere and in a short period while reducing directional bias by using virtual reality goggles, thus making it highly versatile and useful as a practical otolith dysfunction screening tool.
PubMed: 38833295
DOI: 10.2196/53642 -
Journal of the American College of... Jun 2024Diagnostic evaluation of a patient with dizziness or vertigo is complicated by a lack of standardized nomenclature, significant overlap in symptom descriptions, and the...
Diagnostic evaluation of a patient with dizziness or vertigo is complicated by a lack of standardized nomenclature, significant overlap in symptom descriptions, and the subjective nature of the patient's symptoms. Although dizziness is an imprecise term often used by patients to describe a feeling of being off-balance, in many cases dizziness can be subcategorized based on symptomatology as vertigo (false sense of motion or spinning), disequilibrium (imbalance with gait instability), presyncope (nearly fainting or blacking out), or lightheadedness (nonspecific). As such, current diagnostic paradigms focus on timing, triggers, and associated symptoms rather than subjective descriptions of dizziness type. Regardless, these factors complicate the selection of appropriate diagnostic imaging in patients presenting with dizziness or vertigo. This document serves to aid providers in this selection by using a framework of definable clinical variants. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.
Topics: Dizziness; Humans; United States; Societies, Medical; Ataxia; Evidence-Based Medicine; Diagnosis, Differential
PubMed: 38823940
DOI: 10.1016/j.jacr.2024.02.018 -
Journal of Translational Medicine May 2024Dizziness and vertigo rank among the top 10 reasons for emergency and clinical referrals to neurologists. Chronic dizziness and imbalance not only reduce quality of...
BACKGROUND
Dizziness and vertigo rank among the top 10 reasons for emergency and clinical referrals to neurologists. Chronic dizziness and imbalance not only reduce quality of life, but also increase mortality. While the Mediterranean diet has long been considered beneficial for human and planetary health, its effects on chronic dizziness or imbalance are understudied. We investigated the associations of adherence to the Mediterranean diet with chronic dizziness and imbalance.
METHODS
This study used data from the Korea National Health and Nutrition Examination Survey 2019-2021 and included 4,183 adults aged 40 years and older with complete information from diet, dizziness, and neurotology questionnaires. The alternate Mediterranean diet score (aMed) for nine food groups was calculated from 24-hour dietary recall data. Based on questionnaire responses, chronic dizziness was categorized as either isolated or chronic dizziness with imbalance, characterized by a cluster of difficulties maintaining a standing position, walking, or falling.
RESULTS
In a multivariable-adjusted model, the prevalence of chronic imbalance was lower in the top aMed tertile than in the bottom tertile (OR 0.37; 95% CI, 0.18-0.74; p-trend = 0.01). Among the individual aMed components, the intake of whole grains and nuts exhibited an inverse relationship with chronic imbalance (OR 0.50; 95% CI, 0.27-0.93 for whole grains; OR 0.55; 95% CI, 0.31-1.01 for nuts). The aMed score was not associated with isolated chronic dizziness.
CONCLUSIONS
Greater adherence to the Mediterranean diet may reduce chronic imbalance, particularly with an adequate intake of whole grains and nuts.
Topics: Humans; Dizziness; Diet, Mediterranean; Male; Female; Middle Aged; Chronic Disease; Adult; Republic of Korea; Independent Living; Aged; Nutrition Surveys; Postural Balance; Patient Compliance; Surveys and Questionnaires
PubMed: 38822335
DOI: 10.1186/s12967-024-05295-4 -
Neurology and Therapy May 2024Vestibular migraine (VM) is a prevalent vestibular disorder characterized by episodic vertigo. However, the relationship between photophobia and visual triggers in VM...
INTRODUCTION
Vestibular migraine (VM) is a prevalent vestibular disorder characterized by episodic vertigo. However, the relationship between photophobia and visual triggers in VM remains unexplored. We investigated the correlation of photophobia during the VM attack with interictal photosensitivity and visually triggering dizziness in patients with VM.
METHODS
We enrolled patients diagnosed with VM, with or without photophobia, across seven specialized vertigo and headache clinics in China. Healthy individuals were also included as a control group. Using a cross-sectional survey design, we collected data related to light intensity and dizziness frequency triggered by flicker, glare, and eyestrain using the Headache Triggers Sensitivity and Avoidance Questionnaire.
RESULTS
A total of 366 patients were recruited. The photosensitivity and frequency of dizziness induced by flicker, glare, and eyestrain observed in patients with VM and photophobia were significantly elevated compared with those in patients without photophobia and control participants (P < 0.001). A significant positive correlation was observed between photosensitivity levels and dizziness frequency triggered by flicker, glare, and eyestrain in patients with VM and photophobia (P < 0.001).
CONCLUSIONS
This study unequivocally established a positive association of ictal photophobia with interictal photosensitivity and visually triggering dizziness, strongly advocating the need for further research on exposure-based therapies for managing VM.
CLINICAL TRIALS REGISTRATION
ClinicalTrial.gov Identifier, NCT04939922, retrospectively registered, 14th June 2021.
PubMed: 38819614
DOI: 10.1007/s40120-024-00631-8 -
Biomolecules & Biomedicine May 2024Dimenhydrinate (DMH), used to alleviate motion sickness symptoms such as nausea, vomiting, dizziness, and vertigo, encounters limitations in oral pharmaceutical...
Dimenhydrinate (DMH), used to alleviate motion sickness symptoms such as nausea, vomiting, dizziness, and vertigo, encounters limitations in oral pharmaceutical formulations due to its poor water solubility and bitter taste. Our research hypothesized that inclusion complexation with β-cyclodextrin (β-CD) might address these drawbacks while ensuring that the newly formed complexes exhibit no cytotoxic or genotoxic effects on peripheral blood mononuclear cells (PBMCs). Inclusion complexes were prepared using the kneading method and the solvent evaporation method. The phase solubility analysis, attenuated total reflectance-fourier transform infrared spectroscopy (ATR-FTIR), and differential scanning calorimetry (DSC) were conducted to evaluate the complexation efficacy and stability constant of the new binary systems. The results demonstrated that both methods provided complete and efficient complexation. Cytogenotoxic analysis, including the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay, alkaline comet assay, and cytokinesis-block micronucleus cytome (CBMN-cyt) assay, was conducted to assess the cytogenotoxic potential of DMH-β-CD inclusion complexes, a topic previously unexamined. No cytotoxic or genotoxic effects were observed within the concentration range of 36.36 to 109.09 ng/mL. Cell viability of treated PBMCs exceeded 85% for all tested concentrations. No significant increases in DNA strand breaks were observed at any dose, and tail intensity of all complexes remained lower or up to 2.2% higher than the negative control. Parameters indicating genotoxic effects, as well as cytotoxic and cytostatic potential in the CBMN-cyt assay, did not significantly differ from untreated controls. These results suggest that inclusion complexation with β-CD might be a safe and promising solution to overcome the limitations of poor solubility and unpleasant taste of DMH, potentially providing opportunities for new and improved oral pharmaceutical dosage forms.
PubMed: 38819319
DOI: 10.17305/bb.2024.10507