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Journal of Clinical Medicine Aug 2023Ramsay Hunt syndrome (RHS) has a poor prognosis because of varicella-zoster virus (VZV) infection. This is most closely related to severe inflammation in the geniculate...
Ramsay Hunt syndrome (RHS) has a poor prognosis because of varicella-zoster virus (VZV) infection. This is most closely related to severe inflammation in the geniculate ganglion of the facial nerve due to VZV infection or reactivation. This study investigated whether there were differences in the prognosis and accompanying symptoms of facial paralysis based on the presence or absence of VZV IgM and IgG antibodies. This study was conducted as a retrospective chart analysis of 105 patients with RHS who were admitted to our hospital between 2015 and 2021. The House-Brackmann (HB) grade and electroneurography (ENoG) was used to evaluate the degree of facial paralysis. Patients' subjective symptoms were evaluated by dividing them into dizziness, tinnitus, hyperacusis, and hearing loss. No difference was observed in the initial HB grade with or without IgM; however, the final HB grade was significantly higher in IgM-positive patients than in IgM-negative patients ( < 0.05). Further, when IgM was positive, the value of the orbicularis oculi muscle in the ENoG test results was significantly higher ( < 0.05), and symptoms of tinnitus and hyperacusis occurred more frequently ( < 0.05). The initial and final HB grades were significantly higher in IgG-positive patients than in IgG-negative patients ( < 0.05). When IgG was positive, the values of nasalis and oris muscles in the ENoG test results were significantly higher ( < 0.05), and symptoms of dizziness occurred more frequently ( < 0.05). This study confirmed that the more active the immunological action of the VZV in the body, the greater the damage to the facial and vestibulocochlear nerves, which are associated with the degree of facial paralysis and the accompanying otologic symptoms.
PubMed: 37568565
DOI: 10.3390/jcm12155164 -
Cephalalgia : An International Journal... Aug 2023Clinical trials on anti-calcitonin gene-related peptide monoclonal antibodies poorly investigated their impact on migraine accompanying symptoms.
BACKGROUND
Clinical trials on anti-calcitonin gene-related peptide monoclonal antibodies poorly investigated their impact on migraine accompanying symptoms.
OBJECTIVE
To evaluate the impact of basal accompanying symptoms on anti-CGRP monoclonal antibodies treatment response and their evolution after six months of treatment in migraine patients.
METHODS
Patients with migraine diagnosis seen in the Headache Clinic and treated with erenumab, galcanezumab or fremanezumab were prospectively recruited. They completed a daily eDiary which provided data on headache frequency and the following accompanying symptoms of each day: photophobia, phonophobia, nausea, dizziness, and aura. Patients were classified as responders or non-responders based on 50% or greater reduction in headache days per month at month 6 (≥50% response rate). Accompanying symptoms ratios based on headache days per month were assessed per patient at baseline and after three and six months. Comparisons for basal characteristics, basal accompanying symptoms ratios and their evolution after six months between responders and non-responders were performed.
RESULTS
One hundred and fifty-eight patients were included, 44% (69/158) showed ≥50% response rate after six months. A significant reduction in headache days per month in both groups was found at month 6 (-9.4 days/month in ≥50% response rate group; p < 0.001, -2.2 days/month in <50% response rate group; p = 0.004). Additionally, significant decreases in photophobia (-19.5%, p < 0.001), phonophobia (-12.1%, p = 0.010) and aura ratios (-25.1%, p = 0.008) were found in ≥50% response rate group. No statistically significant reductions were found in nausea and dizziness in any group since their reduction was correlated with the decrease in headache days per month. Higher photophobia ratios at baseline were predictive of an increased response between months 3 and 6 (Incidence Risk Ratio = 0.928, p = 0.040).
CONCLUSIONS
The days per month with photophobia, phonophobia and aura decreased at a higher rate than headache days per month after six months in the ≥50% response group. Higher photophobia ratios were associated with higher response rates between three and six months. It could indicate an involvement of peripheral CGRP in photophobia as well as a central modulation of migraine through these treatments which mainly act on the periphery.
Topics: Humans; Antibodies, Monoclonal; Dizziness; Headache; Hyperacusis; Migraine Disorders; Nausea; Photophobia; Treatment Outcome
PubMed: 37555331
DOI: 10.1177/03331024231177636 -
The Laryngoscope Mar 2024Fragile X Syndrome (FXS) is a hereditary form of autism spectrum disorder. It is caused by a trinucleotide repeat expansion in the Fmr1 gene, leading to a loss of...
OBJECTIVE
Fragile X Syndrome (FXS) is a hereditary form of autism spectrum disorder. It is caused by a trinucleotide repeat expansion in the Fmr1 gene, leading to a loss of Fragile X Protein (FMRP) expression. The loss of FMRP causes auditory hypersensitivity: FXS patients display hyperacusis and the Fmr1- knock-out (KO) mouse model for FXS exhibits auditory seizures. FMRP is strongly expressed in the cochlear nucleus and other auditory brainstem nuclei. We hypothesize that the Fmr1-KO mouse has altered gene expression in the cochlear nucleus that may contribute to auditory hypersensitivity.
METHODS
RNA was isolated from cochlear nuclei of Fmr1-KO and WT mice. Using next-generation sequencing (RNA-seq), the transcriptomes of Fmr1-KO mice and WT mice (n = 3 each) were compared and analyzed using gene ontology programs.
RESULTS
We identified 270 unique, differentially expressed genes between Fmr1-KO and WT cochlear nuclei. Upregulated genes (67%) are enriched in those encoding secreted molecules. Downregulated genes (33%) are enriched in neuronal function, including synaptic pathways, some of which are ideal candidate genes that may contribute to hyperacusis.
CONCLUSION
The loss of FMRP can affect the expression of genes in the cochlear nucleus that are important for neuronal signaling. One of these, Kcnab2, which encodes a subunit of the Shaker voltage-gated potassium channel, is expressed at an abnormally low level in the Fmr1-KO cochlear nucleus. Kcnab2 and other differentially expressed genes may represent pathways for the development of hyperacusis. Future studies will be aimed at investigating the effects of these altered genes on hyperacusis.
LEVEL OF EVIDENCE
N/A Laryngoscope, 134:1363-1371, 2024.
Topics: Humans; Mice; Animals; Cochlear Nucleus; Hyperacusis; Autism Spectrum Disorder; Transcriptome; Fragile X Mental Retardation Protein; Fragile X Syndrome; Mice, Knockout; Disease Models, Animal; Shaker Superfamily of Potassium Channels
PubMed: 37551886
DOI: 10.1002/lary.30936 -
PloS One 2023We attempted to replicate a potential tinnitus biomarker in humans based on the Sensory Precision Integrative Model of Tinnitus called the Intensity Mismatch Asymmetry....
We attempted to replicate a potential tinnitus biomarker in humans based on the Sensory Precision Integrative Model of Tinnitus called the Intensity Mismatch Asymmetry. A few advances on the design were also included, including tighter matching of participants for gender, and a control stimulus frequency of 1 kHz to investigate whether any differences between control and tinnitus groups are specific to the tinnitus frequency or domain-general. The expectation was that there would be asymmetry in the MMN responses between tinnitus and control groups at the tinnitus frequency, but not at the control frequency, where the tinnitus group would have larger, more negative responses to upward deviants than downward deviants, and the control group would have the opposite pattern or lack of a deviant direction effect. However, no significant group differences were found. There was a striking difference in response amplitude to control frequency stimuli compared to tinnitus frequency stimuli, which could be an intrinsic quality of responses to these frequencies or could reflect high frequency hearing loss in the sample. Additionally, the upward deviants elicited stronger MMN responses in both groups at tinnitus frequency, but not at the control frequency. Factors contributing to these discrepant results at the tinnitus frequency could include hyperacusis, attention, and wider contextual effects of other frequencies used in the experiment (i.e. the control frequency in other blocks).
Topics: Humans; Evoked Potentials, Auditory; Acoustic Stimulation; Electroencephalography; Tinnitus; Attention
PubMed: 37549154
DOI: 10.1371/journal.pone.0289062 -
The Journal of Headache and Pain Aug 2023Given the similar presentation of migraine aura and acute ischemic stroke, advancing patient age might change the characteristics of migraine with aura (MA) and be...
AIM
Given the similar presentation of migraine aura and acute ischemic stroke, advancing patient age might change the characteristics of migraine with aura (MA) and be clinically important. Clinical data, however, are limited. Experimental studies indicate a decrease in the magnitude of cortical spreading depression (CSD), the pathophysiological correlate of migraine aura, with advancing age. Our study aimed to assess the influence of age on the clinical features of MA.
METHODS
Three hundred and forty-three patients were interviewed using a structured questionnaire. The questions covered the headache characteristics and symptom types including the characteristics of the C-criterion, as defined by the International Classification of Headache Disorders 3 Edition. The association of age with MA characteristics was assessed.
RESULTS
The median age was 29 (IQR 28-52) and 235 of the 343 patients were women (69%). Individual symptoms of the C-criterion such as gradual aura spreading over longer than 5 min (P < 0.001), two or more aura symptoms occurring in succession (P = 0.005), duration of at least one MA symptom for longer than 60 min (P = 0.004), and associated headache (P = 0.01) were more frequent in younger patients. The number of symptoms including the C-characteristics decreased with increasing age (P < 0.001). Patients with sensory (P < 0.001), motor (P = 0.004) and speech disturbance (P = 0.02) were younger, and older patients with headache had less photophobia (P = 0.04) and phonophobia (P = 0.03). Sensitivity analyses yielded similar results.
CONCLUSION
The frequency of typical characteristics of migraine aura and migraine headache including photophobia and phonophobia decreases with advancing patient age. This might have potentially difficult implications for the diagnosis of MA in the elderly.
Topics: Humans; Female; Aged; Adult; Male; Migraine with Aura; Ischemic Stroke; Hyperacusis; Photophobia; Migraine Disorders; Epilepsy; Headache
PubMed: 37528414
DOI: 10.1186/s10194-023-01642-w -
International Journal of Molecular... Jul 2023Hyperacusis, i.e., an increased sensitivity to sounds, is described in several neurodevelopmental disorders (NDDs), including Fragile X Syndrome (FXS). The mechanisms...
Hyperacusis, i.e., an increased sensitivity to sounds, is described in several neurodevelopmental disorders (NDDs), including Fragile X Syndrome (FXS). The mechanisms underlying hyperacusis in FXS are still largely unknown and effective therapies are lacking. Big conductance calcium-activated potassium (BKCa) channels were proposed as a therapeutic target to treat several behavioral disturbances in FXS preclinical models, but their role in mediating their auditory alterations was not specifically addressed. Furthermore, studies on the acoustic phenotypes of FXS animal models mostly focused on central rather than peripheral auditory pathways. Here, we provided an extensive characterization of the peripheral auditory phenotype of the -knockout (KO) mouse model of FXS at adulthood. We also assessed whether the acute administration of Chlorzoxazone, a BKCa agonist, could rescue the auditory abnormalities of adult mutant mice. -KO mice both at 3 and 6 months showed a hyperacusis-like startle phenotype with paradoxically reduced auditory brainstem responses associated with a loss of ribbon synapses in the inner hair cells (IHCs) compared to their wild-type (WT) littermates. BKCa expression was markedly reduced in the IHCs of KOs compared to WT mice, but only at 6 months, when Chlorzoxazone rescued mutant auditory dysfunction. Our findings highlight the age-dependent and progressive contribution of peripheral mechanisms and BKCa channels to adult hyperacusis in FXS, suggesting a novel therapeutic target to treat auditory dysfunction in NDDs.
Topics: Animals; Mice; Auditory Pathways; Chlorzoxazone; Disease Models, Animal; Fragile X Mental Retardation Protein; Fragile X Syndrome; Hyperacusis; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; Mice, Knockout
PubMed: 37511622
DOI: 10.3390/ijms241411863 -
Brain Sciences Jul 2023Background noise elicits listening effort. What else is tinnitus if not an endogenous background noise? From such reasoning, we hypothesized the occurrence of increased...
Listening Effort in Tinnitus: A Pilot Study Employing a Light EEG Headset and Skin Conductance Assessment during the Listening to a Continuous Speech Stimulus under Different SNR Conditions.
Background noise elicits listening effort. What else is tinnitus if not an endogenous background noise? From such reasoning, we hypothesized the occurrence of increased listening effort in tinnitus patients during listening tasks. Such a hypothesis was tested by investigating some indices of listening effort through electroencephalographic and skin conductance, particularly parietal and frontal alpha and electrodermal activity (EDA). Furthermore, tinnitus distress questionnaires (THI and TQ12-I) were employed. Parietal alpha values were positively correlated to TQ12-I scores, and both were negatively correlated to EDA; Pre-stimulus frontal alpha correlated with the THI score in our pilot study; finally, results showed a general trend of increased frontal alpha activity in the tinnitus group in comparison to the control group. Parietal alpha during the listening to stimuli, positively correlated to the TQ12-I, appears to reflect a higher listening effort in tinnitus patients and the perception of tinnitus symptoms. The negative correlation between both listening effort (parietal alpha) and tinnitus symptoms perception (TQ12-I scores) with EDA levels could be explained by a less responsive sympathetic nervous system to prepare the body to expend increased energy during the "fight or flight" response, due to pauperization of energy from tinnitus perception.
PubMed: 37509014
DOI: 10.3390/brainsci13071084 -
Audiology Research Jul 2023Migraine is a chronic neurological disorder that frequently coexists with different vestibular and cochlear symptoms (sudden hearing loss, tinnitus, otalgia, aural... (Review)
Review
Migraine is a chronic neurological disorder that frequently coexists with different vestibular and cochlear symptoms (sudden hearing loss, tinnitus, otalgia, aural fullness, hyperacusis, dizziness, imbalance, and vertigo) and disorders (recurrent benign positional vertigo, persistent postural perceptual dizziness, mal de debarquement, and Menière's disease). Despite evidence of an epidemiological association and similar pathophysiology between migraine and these vestibulocochlear disorders, patients suffering from migraine-related symptoms are usually underdiagnosed and undertreated. Current migraine treatment options have shown success in treating vestibulocochlear symptoms. Lifestyle and dietary modifications (reducing stress, restful sleep, avoiding migraine dietary triggers, and avoiding starvation and dehydration) and supplements (vitamin B2 and magnesium) offer effective first-line treatments. Treatment with migraine prophylactic medications such as tricyclic antidepressants (e.g., nortriptyline), anticonvulsants (e.g., topiramate), and calcium channel blockers (e.g., verapamil) is implemented when lifestyle and dietary modifications are not sufficient in improving a patient's symptoms. We have included an algorithm that outlines a suggested approach for addressing these symptoms, taking into account our clinical observations. Greater recognition and understanding of migraine and its related vestibular and cochlear symptoms are needed to ensure the appropriate diagnosis and treatment of affected patients.
PubMed: 37489383
DOI: 10.3390/audiolres13040047 -
Audiology Research Jul 2023Identifying a vestibular source of pathology in patients complaining of post-traumatic brain injury (TBI) dizziness can be difficult. We describe a possible new method...
Identifying a vestibular source of pathology in patients complaining of post-traumatic brain injury (TBI) dizziness can be difficult. We describe a possible new method utilizing a reduction in post-TBI symptoms (including dizziness) with the use of a noise cancellation device (NCD). This retrospective case series included patients with TBI and dizziness presenting to a binocular vision specialty clinic, who were diagnosed with a vertical heterophoria (VH). If they did not respond adequately to microprism lenses and/or if they experienced hyperacusis, they were evaluated with an NCD. If there was marked reduction in TBI symptoms (including dizziness), the patients were referred to a neuro-otologist for vestibular diagnostic evaluation and treatment. Fourteen patients were identified and found to have abnormalities on vestibular testing consistent with third mobile window disorder (TMWD). All were treated with a 6-week medical protocol (diuretics, no straining, low sodium/no caffeine diet). Five responded positively, requiring no further treatment. Nine required surgical intervention and responded positively. In conclusion, in 14 patients with post-concussive dizziness and VH, a positive response to NCD was associated with abnormal vestibular testing, a diagnosis of TMWD, and symptom reduction/resolution with a medical or surgical approach. The removal of sound resulting in reduction or resolution of vestibular symptoms represents an inverse Tullio phenomenon.
PubMed: 37489382
DOI: 10.3390/audiolres13040046