Clinical Significance of Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio in Acute Unilateral Vestibulopathy.

BACKGROUND AND PURPOSE: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been identified as useful biomarkers for assessing the inflammatory response and for predicting the prognosis of various diseases. This study aimed to determine the clinical significance and effects on prognostic prediction of NLR and PLR in acute unilateral vestibulopathy (AUV). METHODS: We retrospectively recruited 128 patients who were diagnosed with AUV from July 2016 to April 2021, and compared NLR and PLR values between these patients with AUV and age- and sex-matched healthy subjects. We also analyzed the correlations of various clinical parameters with NLR and PLR. RESULTS: NLR and PLR in the AUV group were 3.41±2.80 (mean±standard deviation) and 128.86±67.06, respectively, with only NLR being significantly higher than that in the control group (1.55±0.60, p<0.001). The gain asymmetry of the horizontal vestibulo-ocular reflex (VOR) was slightly larger in patients with high NLR (n=52) than in those with normal NLR (n=76) (41.9%±20.2% vs. 33.6%±17.4%, p=0.048). However, the hospitalization period, preceding infection, canal paresis, and absolute horizontal VOR gain did not differ between patients with high and normal NLR and PLR values. The correlation analyses also revealed that none of the clinical parameters were significantly correlated with NLR or PLR. At 3-month follow-up examinations, NLR and PLR did not differ significantly between patients with and without function recovery of the horizontal VOR. CONCLUSIONS: This study found a high NLR in AUV, suggesting an acute inflammatory status in the vestibular organ. However, the usefulness of NLR and PLR as prognostic markers remains unclear.

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.

Ocular motor and vestibular dysfunction in central nervous system lymphoma.

BACKGROUND AND PURPOSE: Diagnosis of lymphoma involving the central nervous system (CNS) is challenging. This study aimed to explore the abnormal vestibular and ocular motor findings in CNS lymphoma. METHODS: A retrospective search of the medical records identified 30 patients with CNS lymphoma presenting ocular motor and vestibular abnormalities from four neurology clinics of university hospitals in South Korea (22 men, age range 14-81 years, mean 60.6 ± 15.2). The demographic and clinical features and the results of laboratory, radiological and pathological evaluation were analyzed. RESULTS: Patients presented with diplopia (13/30, 43%), vestibular symptoms (15/30, 50%) or both (2/30, 7%). In 15 patients with diplopia, abnormal ocular motor findings included ocular motor nerve palsy (n = 10, 67%), internuclear ophthalmoplegia (n = 2, 13%), external ophthalmoplegia (n = 2, 13%) and exophoria (n = 1, 7%). The vestibular abnormalities were isolated in 14 (82%) of 17 patients with vestibular symptoms and included combined unilateral peripheral and central vestibulopathy in three from lesions involving the vestibular nuclei. CNS lymphoma involved the brainstem (53%), cerebellum (33%), leptomeninges (30%), deep gray nuclei (23%) or cranial nerves (17%). Two patients showed the "double-panda" sign by involving the midbrain. CONCLUSIONS: This study expands the clinical and radiological spectra of CNS lymphoma. Neuro-ophthalmological and neuro-otological evaluation may guide the early diagnosis of CNS lymphoma.

Abnormal vestibular-evoked myogenic potentials as a risk factor for unpredicted falls in spinocerebellar ataxia: a preliminary study.

OBJECTIVE: This study aimed to correlate the symptoms and signs with the findings of laboratory vestibular function tests in patients with spinocerebellar ataxia (SCA). METHOD: We retrospectively recruited 26 patients with SCA (9 men, median age: 52, age range: 21-67). Assessments included Dizziness Handicap Inventory, EuroQoL Five-Dimension, symptom questionnaires manifesting during walking in daily life, the Scale for the Assessment and Rating of Ataxia (SARA), and vestibular function tests including 3D video-oculography, video head impulse test, subjective visual vertical, and cervical and ocular vestibular evoked myogenic potentials (VEMP). RESULTS: Cross-analyses revealed that the patients with VEMP abnormalities showed higher SARA (p = 0.014) and prevalence of unpredictable falls (p = 0.046). The patients with SCA1 more frequently had unpredictable falls (75%, p = 0.038) and VEMP abnormalities (88%, p = 0.001) compared to SCA2 (29% falls, 17% VEMP abnormalities) and SCA6 (no falls or VEMP abnormalities). CONCLUSION: Abnormal VEMPs are strongly associated with unpredicted falls in patients with SCA, particularly in those with SCA1. Impaired processing of otolithic information may contribute to falls in SCAs, and VEMP may help identifying the patients with a risk for unpredicted falls and preventing fall-related injuries in SCA. Limited number of patients with lower SARA scores warrant further confirmatory studies.

A Comparison of the Condyle and Articular Eminence in Asian Juvenile Idiopathic Osteoarthritis Patients with Unilateral and Bilateral TMJ Involvement: A Retrospective Case-Control Study.

This study compared the condylar volume, length, and articular eminence (AE) characteristics of normal individuals to those with unilateral and bilateral juvenile idiopathic osteoarthritis (JOA). The 116 patients were divided into four groups: Control (n = 16), affected condyle of unilateral JOA (Aff-Uni) (n = 36), non-affected condyle of JOA (NonAff-uni) (n = 36), and bilateral JOA (Bilateral) (n = 28). The differences in condyle volume and length and AE were analyzed using ANOVA and Bonferroni post-hoc tests. The results showed that Bilateral had a significantly different condylar volume, especially in the condylar head (p < 0.01), specifically the middle, anterior, and medial parts (p < 0.05). Condylar length also differed among the groups, with differences observed between the control group and the other three groups, as well as between the bilateral group and the other three groups (p < 0.01). AE total volume differed between the control group and Aff-Uni. In the detailed comparison, Aff-Uni and NonAff-Uni were smaller than the control group in the posterior, lateral, and medial sections (p < 0.05). In conclusion, depending on the involvement of unilateral or bilateral JOA, there were differences in condylar volume and AE when compared to the normal control group. Therefore, a prognosis should be evaluated by distinguishing between patients with unilateral and bilateral JOA.

Gene expression analysis in recurrent benign paroxysmal positional vertigo: a preliminary study.

Objectives: This study aimed to determine the pathophysiology of recurrent benign paroxysmal positional vertigo (BPPV) in young patients using gene expression profiling combined with bioinformatics analysis. Methods: Total RNA was extracted from the whole blood of four young patients with recurrent BPPV and four controls. The differentially expressed genes (DEGs) between the groups were screened using a microarray analysis based on the cutoff criteria of |log2 fold change| > 1 and an adjusted p-value of < 0.05. Functional enrichment analysis of DEGs was performed using Gene Ontology analysis, and the protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of the Interacting Genes database. Results: A total of 39 DEGs were detected between the BPPV and control samples, comprising 33 upregulated DEGs and six downregulated DEGs in the BPPV group. Functional enrichment analysis indicated that the upregulated DEGs were significantly enriched in terms related to metabolic processes and the immune system. Two main pathways were extracted from the PPI network: one was associated with oxidative phosphorylation and stress and the other with the adaptive immune system and extracellular matrix degradation. Conclusion: The findings of our bioinformatics analysis indicated that oxidative stress or extracellular matrix degradation due to immune-mediated inflammatory responses may contribute to the development of recurrent BPPV in young patients.

Sequential orbital apex syndrome following the COVID-19 vaccination: A case report.

Background: Many kinds of vaccines have been developed worldwide to bring the coronavirus disease 2019 (COVID-19) to an end. We report a case of recurrent orbital apex syndrome following the first and third doses of SARS-CoV-2 vaccination. Case presentation: A 71-year-old woman presented with acute painless diplopia and visual disturbance for two days. She had received the first dose of the COVID-19 vaccine two weeks before. She showed decreased visual acuity and ophthalmoplegia in the right eye. An orbital magnetic resonance image (MRI) revealed a hyperintense lesion with enhanced bulging in the right cavernous sinus. Following the steroid pulse therapy, she fully recovered. However, six months after the first attack, painful ophthalmoplegia with decreased visual acuity recurred in her left eye after the booster vaccination for COVID-19. MRI also showed a well-enhanced hyperintense lesion in the left orbital apex. Fortunately, her visual acuity and ocular motility returned to normal after the steroid therapy. Conclusions: Immunologic reactions from COVID-19 vaccines may cause multiple cranial neuropathies. Diverse individual immunologic states should be considered before any kind of vaccine.

Effect of Self-treatment of Recurrent Benign Paroxysmal Positional Vertigo: A Randomized Clinical Trial.

Importance: Benign paroxysmal positional vertigo (BPPV) is the most common cause of vertigo with frequent recurrences. Objective: To determine the efficacy of a web-based diagnosis and treatment of BPPV when it recurs in patients with confirmed and treated BPPV. Design, Setting, and Participants: This randomized, controlled, parallel-group, double-blind trial took place in multiple referral-based university hospitals in South Korea between July 2017 and February 2020. Of 728 patients (age ≥20 years) with diagnosed and treated BPPV, 585 were enrolled after excluding 143 who declined participation, could not use the internet, or had spinal problems, multicanal BPPV, or cognitive dysfunction. Patients were followed up for recurrence at least for 2 years until February 2022. Interventions: Patients were randomly assigned (1:1) to the treatment or control group. The patients in the treatment group completed a questionnaire for diagnosis and received a video clip for self-administration of canalith repositioning maneuver (CRM) according to the type of BPPV diagnosed when they experienced positional vertigo again. Patients in the control group received a video clip for self-administration of CRM according to the type of BPPV that had been diagnosed on enrollment. Main Outcomes and Measures: The primary outcome was self-reported resolution of positional vertigo post-CRM. Secondary outcomes included difficulties and requirement for assistance when using the program and any falls or other adverse events related to CRM. The primary outcome was analyzed using both intention-to-treat and per-protocol methods. Results: Of 585 patients enrolled, 292 were randomized to the treatment group (mean [SD] age, 60.3 [12.8] years, 37 [64%] women) and 293 were randomized to the control group (mean [SD] age, 61.1 [13.2] years; 50 [71%] women). Overall, 128 (21.9%) had recurrence (58 in the treatment group and 70 in the control group), and 109 (85.2%) successfully used the web-based system. In the intention-to-treat analysis, 42 of 58 individuals (72.4%) in the treatment group and 30 of 70 individuals (42.9%) in the control group reported vertigo resolution (χ2 test: 95% CI, 0.13-0.46; P < .001). Conclusions and Relevance: This trial proved the efficacy of a web-based system for the diagnosis and treatment of recurrent BPPV. Use of this system may play an important role in telemedicine for vestibular disorders. Trial Registration: Clinical Research Information Service Identifier: KCT0002364.

Incidence, characteristics, and neuroanatomical substrates of vestibular symptoms in supratentorial stroke.

The incidence and characteristics of acute vestibular symptoms, responsible structures, and lateralization of the causative lesions in supratentorial stroke remain unknown. This study aimed to determine the incidence, clinical features, and anatomical correlation of acute vestibular symptoms in supratentorial stroke. We performed a prospective, multicenter, observational study that had recruited patients with supratentorial stroke from the neurology clinics of referral-based four university hospitals in Korea. All patients received a constructed neuro-otological evaluations, and neuroimaging. We analyzed the incidence of acute vestibular symptoms, abnormal ocular motor and vestibular function tests, and stroke lesions. Of 1301 patients with supratentorial stroke, 48 (3.7%) presented with acute vestibular symptoms, and 13 of them (1%) had the vestibular symptoms in isolation. In patients with acute vestibular symptoms, abnormal findings included spontaneous nystagmus (5%), impaired horizontal smooth pursuit (41%), and abnormal tilt of the subjective visual vertical (SVV) (20%). Video head impulse and caloric tests were normal in all the patients. There was no clear correlation between acute vestibular symptoms and involvement of specific vestibular cortex. In patients with unilateral stroke, there was also no lateralization of the causative lesions of acute vestibular symptoms (left vs. right; 52 vs. 48%), even in patients with vertigo (left vs. right; 58 vs. 42%). This study demonstrates that the incidence of acute vestibular symptoms in supratentorial stroke is 3.7%, with being isolated in 1%. The widespread lesions responsible for acute vestibular symptoms implicate diffuse multisensory cortical-subcortical networks in the cerebral hemispheres without a lateralization.

Chrysanthemum boreale Makino Inhibits Oxidative Stress-Induced Neuronal Damage in Human Neuroblastoma SH-SY5Y Cells by Suppressing MAPK-Regulated Apoptosis.

Oxidative stress has been demonstrated to play a pivotal role in the pathological processes of many neurodegenerative diseases. In the present study, we demonstrated that Chrysanthemum boreale Makino extract (CBME) suppresses oxidative stress-induced neurotoxicity in human neuroblastoma SH-SY5Y cells and elucidated the underlying molecular mechanism. Our observations revealed that CBME effectively protected neuronal cells against H2O2-induced cell death by preventing caspase-3 activation, Bax upregulation, Bcl-2 downregulation, activation of three mitogen-activated protein kinases (MAPKs), cAMP response element-binding protein (CREB) and NF-κB phosphorylation, and iNOS induction. These results provide evidence that CBME has remarkable neuroprotective properties in SH-SY5Y cells against oxidative damage, suggesting that the complementary or even alternative role of CBME in preventing and treating neurodegenerative diseases is worth further studies.

Transcriptional Down-Regulation of Major Histocompatibility Complex as a Possible Pathogenesis for Meniere's Disease.

Objectives: This study aimed to determine the underlying pathogenesis of Meniere's disease (MD) using transcriptome analysis. Methods: Total RNA was extracted from the peripheral blood mononuclear cells of 39 patients with MD and 39 controls. Through microarray analysis for nine patients and controls, the differentially expressed genes (DEGs) of those two groups were screened based on cut-off criteria (|fold changes| > 2.0 and adjusted p-value < 0.05). The functional enrichment analysis of DEGs was performed using Gene Ontology (GO). Results: There were 996 DEGs identified in the MD group: 415 were upregulated and 581 were downregulated. A functional enrichment analysis indicated that the downregulated DEGs were significantly enriched in terms related to immune system processes. Among them, 17 genes were enriched in terms for the major histocompatibility complex (MHC) protein complex, and the relative messenger RNA (mRNA) levels of three markedly downregulated DEGs [fold changes < -5: human leukocyte antigen (HLA)-DMA, HLA-DRB1, and HLA-DPB1] were significantly decreased in another 30 patients with MD compared with normal controls by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). However, there were no correlations between the expression levels of these three genes and clinical data, such as age, onset age, time course, or hearing threshold. Conclusions: Our transcriptome analysis showed that the downregulated DEGs in MD were mainly associated with the immune system pathways including the MHC protein complex in MD. Remarkably, a breakdown in immunological tolerance mediated by MHC class II may contribute to the MD development, which has implications for targeted treatment.

Initial Healing Effects of Platelet-Rich Plasma (PRP) Gel and Platelet-Rich Fibrin (PRF) in the Deep Corneal Wound in Rabbits.

Platelet concentrates (PCs), including platelet-rich plasma (PRP) gel and platelet-rich fibrin (PRF), are autologous blood-derived biomaterials containing numerous growth factors. This study aimed to evaluate the initial healing effects of PRP gel and PRF on deep corneal wounds. Thirty-three eyes from New Zealand white rabbits were divided into four groups: group 1, lamellar keratectomy (LK); group 2, LK + commercial porcine small intestinal submucosal membrane (SIS); group 3, LK + SIS + PRP gel; and group 4, LK + SIS + PRF. Postoperative clinical and histological findings were observed for eight weeks. Group 1 showed no neovascularization during the observation period, and incompletely recovered with a thin cornea. Group 2 showed active healing through neovascularization, and a thick cornea was regenerated through the sufficient generation of myofibroblasts. Although group 3 showed a healing effect similar to that of group 2, angiogenesis and subsequent vessel regression were promoted, and corneal opacity improved more rapidly. In group 4, angiogenesis was promoted during initial healing; however, the incidence of complications, such as inflammation, was high, and myofibroblasts were hardly generated in the corneal stroma, which adversely affected remodeling. In conclusion, while PRP gel is a safe surgical material for promoting remodeling through vascular healing and myofibroblast production in deep corneal wounds, the use of PRF is not recommended.

Acute vertical pendular nystagmus: eye-movement analysis and review of the literature.

Vertical pendular nystagmus (PN) rarely occurs with acute pontine lesions. To hypothesize a pathophysiology for acute vertical PN, we analyzed the clinical characteristics and quantitative eye-movement recordings of one new case with acute vertical PN and an additional 11 patients from the literature. Most patients had extensive pontine lesions causing either the locked-in syndrome or unresponsiveness, but two conscious patients had focal lesions restricted to the paramedian caudal pontine tegmentum. All patients presented a complete or partial horizontal gaze palsy, and about half showed ocular bobbing before or during the appearance of vertical PN. The vertical oscillations were conjugate at a frequency of 1-5 Hz, and the amplitudes were variable, ranging from 0.2° to 40°. The peak velocities were asymmetric in some patients, faster with downward movements. About half of the patients developed palatal tremor several weeks or months after presenting with acute vertical PN. Based on the location of the lesions and results of eye-movement recordings, we suggest two possible mechanisms for acute vertical PN; oscillations originating in the inferior olives due to disruption of the central tegmental tract or low-velocity saccadic oscillations caused by omnipause neuron damage.

Discordant vestibulo-ocular reflex function according to the frequency and mode of stimulation.

This study aimed to determine the incidence, pattern, and etiology of dissociated vestibulo-ocular reflex (VOR) function according to the stimulus frequency in dizzy patients. We retrospectively evaluated the results of bithermal caloric tests and video-head impulse tests (vHITs) in 1022 patients with dizziness or vertigo between July 2016 and April 2021. Patients were classified into concordant group (normal or abnormal results on both tests) and discordant group (dissociated results between two tests). Of 1022 patients, discordant group had 159 (16%), comprising abnormal horizontal vHITs with normal caloric responses (n = 36, 23%) and abnormal caloric tests with normal horizontal vHITs (n = 123, 77%). The former group showed similar frequency of peripheral (44%) and central (42%) causes, and more common involvement of bilateral horizontal semicircular canals in central than peripheral causes (86.7 vs 37.5%, p = 0.005). The most common peripheral causes were Meniere's disease and chronic vestibular neuritis, while central causes were variable, but mainly affecting the cerebellum. In the latter group, peripheral causes were common (67%), with the main etiologies being Meniere's disease and vestibular neuritis, whereas central causes were found in only 5%. The degree of canal paresis did not differ significantly between patients with central and peripheral causes. Discordant VOR function according to the stimulus frequency was not uncommon in dizzy patients. Specific patterns of VOR dissociation according to the disease etiologies may offer insight into underlying pathophysiology.

Erratum: Isolated Vestibular Syndrome With "Double-Panda" Sign in CNS Lymphoma.

This corrects the article on p. 111 in vol. 18, PMID: 35021288.

Vestibular impairments in episodic ataxia type 2.

Episodic ataxia type 2 (EA2) can present diverse ocular motor abnormalities, but few studies have systematically evaluated vestibular function during the interictal periods. This study aimed to determine vestibular impairments in patients with EA2 during the interictal periods. We recruited 17 patients with genetically confirmed EA2 (10 men, age range = 16-85 years, median = 32 years). We systematically evaluated the vestibular function by measuring the semicircular canals (SCCs) function with bithermal caloric tests, rotatory chair test, and video head impulse test (vHIT), and the otolith function with subjective visual vertical (SVV) tilt and variability, and cervical and ocular vestibular-evoked myogenic potentials (VEMPs). Patients with EA2 commonly showed abnormal VOR responses at least for one SCC with high-acceleration, high-frequency head impulses (14/16, 88%), and impaired visual-vestibular interaction (7/12, 58%). In response to low acceleration and frequency stimuli, the VOR gains were generally normal. The majority of EA2 patients had impairments in at least one of the otolith function tests (13/16, 81%): SVV tilt or variability (7/14, 50%), oVEMP (8/15, 53%), and cVEMP (4/16, 25%). Vestibular impairments are common in EA2 even during the interictal periods. Selective decrease in the VOR responses during higher acceleration stimuli along with impaired visual-vestibular interaction and otolith function suggests degeneration of the vestibulocerebellum or vestibular nuclei.