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The Journal of Headache and Pain Aug 2023It is unknown whether new daily persistent headache (NDPH) is a single disorder or heterogenous group of disorders, and whether it is a unique disorder from chronic...
BACKGROUND
It is unknown whether new daily persistent headache (NDPH) is a single disorder or heterogenous group of disorders, and whether it is a unique disorder from chronic migraine and chronic tension-type headache. We describe a large group of patients with primary NDPH, compare its phenotype to transformed chronic daily headache (T-CDH), and use cluster analysis to reveal potential sub-phenotypes in the NDPH group.
METHODS
We performed a case-control study using prospectively collected clinical data in patients with primary NDPH and T-CDH (encompassing chronic migraine and chronic tension-type headache). We used logistic regression with propensity score matching to compare demographics, phenotype, comorbidities, and treatment responses between NDPH and T-CDH. We used K-means cluster analysis with Gower distance to identify sub-clusters in the NDPH group based on a combination of demographics, phenotype, and comorbidities.
RESULTS
We identified 366 patients with NDPH and 696 with T-CDH who met inclusion criteria. Patients with NDPH were less likely to be female (62.6% vs. 73.3%, p < 0.001). Nausea, vomiting, photophobia, phonophobia, motion sensitivity, vertigo, and cranial autonomic symptoms were all significantly less frequent in NDPH than T-CDH (p value for all < 0.001). Acute treatments appeared less effective in NDPH than T-CDH, and medication overuse was less common (16% vs. 42%, p < 0.001). Response to most classes of oral preventive treatments was poor in both groups. The most effective treatment in NDPH was doselupin in 45.7% patients (95% CI 34.8-56.5%). Cluster analysis identified three subgroups of NDPH. Cluster 1 was older, had a high proportion of male patients, and less severe headaches. Cluster 2 was predominantly female, had severe headaches, and few associated symptoms. Cluster 3 was predominantly female with a high prevalence of migrainous symptoms and headache triggers.
CONCLUSIONS
Whilst there is overlap in the phenotype of NDPH and T-CDH, the differences in migrainous, cranial autonomic symptoms, and vulnerability to medication overuse suggest that they are not the same disorder. NDPH may be fractionated into three sub-phenotypes, which require further investigation.
Topics: Female; Male; Humans; Tension-Type Headache; Case-Control Studies; Headache Disorders; Headache; Migraine Disorders; Phenotype
PubMed: 37587430
DOI: 10.1186/s10194-023-01639-5 -
Frontiers in Neuroscience 2021
PubMed: 34335173
DOI: 10.3389/fnins.2021.700670 -
Trends in Hearing 2018Acoustic shocks and traumas sometimes result in a cluster of debilitating symptoms, including tinnitus, hyperacusis, ear fullness and tension, dizziness, and pain in and... (Review)
Review
Acoustic shocks and traumas sometimes result in a cluster of debilitating symptoms, including tinnitus, hyperacusis, ear fullness and tension, dizziness, and pain in and outside the ear. The mechanisms underlying this large variety of symptoms remain elusive. In this article, we elaborate on the hypothesis that the tensor tympani muscle (TTM), the trigeminal nerve (TGN), and the trigeminal cervical complex (TCC) play a central role in generating these symptoms. We argue that TTM overuse (due to the acoustic shock), TTM overload (due to muscle tension), and ultimately, TTM injury (due to hypoxia and "energy crisis") lead to inflammation, thereby activating the TGN, TCC, and cortex. The TCC is a crossroad structure integrating sensory inputs coming from the head-neck complex (including the middle ear) and projecting back to it. The multimodal integration of the TCC may then account for referred pain outside the ear when the middle ear is inflamed and activates the TGN. We believe that our model proposes a synthetic and explanatory framework to explain the phenomena occurring postacoustic shock and potentially also after other nonauditory causes. Indeed, due to the bidirectional properties of the TCC, musculoskeletal disorders in the region of the head-neck complex, including neck injury due to whiplash or temporomandibular disorders, may impact the middle ear, thereby leading to otic symptoms. This previously unavailable model type is experimentally testable and must be taken as a starting point for identifying the mechanisms responsible for this particular subtype of tinnitus and its associated symptoms.
Topics: Cluster Analysis; Ear, Middle; Earache; Female; Humans; Hyperacusis; Male; Shock; Temporomandibular Joint Disorders; Tensor Tympani; Tinnitus; Trigeminal Nerve
PubMed: 30249168
DOI: 10.1177/2331216518801725 -
Journal of the Association For Research... Feb 2024To assess the available evidence to support a genetic contribution and define the role of common and rare variants in tinnitus.
PURPOSE
To assess the available evidence to support a genetic contribution and define the role of common and rare variants in tinnitus.
METHODS
After a systematic search and quality assessment, 31 records including 383,063 patients were selected (14 epidemiological studies and 17 genetic association studies). General information on the sample size, age, sex, tinnitus prevalence, severe tinnitus distribution, and sensorineural hearing loss was retrieved. Studies that did not include data on hearing assessment were excluded. Relative frequencies were used for qualitative variables to compare different studies and to obtain average values. Genetic variants and genes were listed and clustered according to their potential role in tinnitus development.
RESULTS
The average prevalence of tinnitus estimated from population-based studies was 26.3% for any tinnitus, and 20% of patients with tinnitus reported it as an annoying symptom. One study has reported population-specific differences in the prevalence of tinnitus, the white ancestry being the population with a higher prevalence. Genome-wide association studies have identified and replicated two common variants in the Chinese population (rs2846071; rs4149577) in the intron of TNFRSF1A, associated with noise-induced tinnitus. Moreover, gene burden analyses in sequencing data from Spanish and Swede patients with severe tinnitus have identified and replicated ANK2, AKAP9, and TSC2 genes.
CONCLUSIONS
The genetic contribution to tinnitus is starting to be revealed and it shows population-specific effects in European and Asian populations. The common allelic variants associated with tinnitus that showed replication are associated with noise-induced tinnitus. Although severe tinnitus has been associated with rare variants with large effect, their role on hearing or hyperacusis has not been established.
Topics: Humans; Tinnitus; Genome-Wide Association Study; Hearing; Hearing Loss, Sensorineural; Hyperacusis
PubMed: 38334885
DOI: 10.1007/s10162-024-00925-6 -
Frontiers in Neurology 2017Superior semicircular canal dehiscence syndrome was first reported by Lloyd Minor and colleagues in 1998. Patients with a dehiscence in the bone overlying the superior... (Review)
Review
Superior semicircular canal dehiscence syndrome was first reported by Lloyd Minor and colleagues in 1998. Patients with a dehiscence in the bone overlying the superior semicircular canal experience symptoms of pressure or sound-induced vertigo, bone conduction hyperacusis, and pulsatile tinnitus. The initial series of patients were diagnosed based on common symptoms, a physical examination finding of eye movements in the plane of the superior semicircular canal when ear canal pressure or loud tones were applied to the ear, and high-resolution computed tomography imaging demonstrating a dehiscence in the bone over the superior semicircular canal. Research productivity directed at understanding better methods for diagnosing and treating this condition has substantially increased over the last two decades. We now have a sound understanding of the pathophysiology of third mobile window syndromes, higher resolution imaging protocols, and several sensitive and specific diagnostic tests. Furthermore, we have a treatment (surgical occlusion of the superior semicircular canal) that has demonstrated efficacy. This review will highlight some of the fundamental insights gained in SCDS, propose diagnostic criteria, and discuss future research directions.
PubMed: 28503164
DOI: 10.3389/fneur.2017.00177 -
PloS One 2023Recently, the most bothersome symptom has been recommended as a co-primary endpoint in clinical trials on the acute treatment of migraine. Probable migraine is a subtype...
Recently, the most bothersome symptom has been recommended as a co-primary endpoint in clinical trials on the acute treatment of migraine. Probable migraine is a subtype of migraine that fulfills all but one criterion for migraine diagnosis. We aimed to compare the most bothersome symptom between probable migraine and migraine. This study analyzed data from a nationwide study conducted in Korea, and the most bothersome symptom was assessed by requesting the participants to select one of the four typical accompanying symptoms of migraine. Responses to acute treatment were evaluated using the migraine Treatment Optimization Questionnaire-6. Nausea was the most bothersome symptom, followed by phonophobia and vomiting in the migraine group (nausea, 61.8%; phonophobia, 25.3%; vomiting, 10.0%; and photophobia, 2.9%) and the probable migraine group (nausea, 82.2%; phonophobia, 9.5%; vomiting, 5.6%; and photophobia, 2.7%). In participants with migraine, vomiting (adjusted odds ratio = 6.513; 95% confidence interval, 1.763-24.057) and phonophobia (adjusted odds ratio = 0.437; 95% confidence interval, 0.206-0.929) were significantly associated with severe headache intensity and nausea was significantly associated with >3 headache days per 30 days (adjusted odds ratio = 0.441; 95% confidence, 0.210-0.927). Different patterns of associations were observed in probable migraine.
Topics: Humans; Photophobia; Hyperacusis; Migraine Disorders; Nausea; Vomiting; Headache; Surveys and Questionnaires; Double-Blind Method
PubMed: 38019845
DOI: 10.1371/journal.pone.0289729 -
Ideggyogyaszati Szemle Sep 2023
Migraine as a common primary headache disorder has a significant negative effect on quality of life of the patients. Its pharmacotreatment includes acute and... (Review)
Review
Migraine as a common primary headache disorder has a significant negative effect on quality of life of the patients. Its pharmacotreatment includes acute and preventative therapies. Based on the shared therapeutic guideline of the European Headache Federation and the European Academy of Neurology for acute migraine treatment a combination of triptans and non-steroidal anti-inflammatory drugs is recommended for acute migraine treatment in triptan-nonresponders. In this short review we summarized the results of the randomized controlled clinical trials evaluating the effectiveness and safety of sumatriptan (85 mg)/naproxen sodium (500 mg) fix-dose combination. It was revealed that the fix-dose combination was better than placebo for the primary outcomes of exemption of pain and headache relief at 2 hours. Furthermore the combination showed beneficial effect on accompanying symptoms of migraine attack (i.e. nausea, photo- and phonophobia). Adverse events were mild or moderate in severity and rarely led to withdrawal of the drug.
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It can be concluded that sumatriptan (85 mg)/naproxen sodium (500 mg) fix-dose combination is effective, safe and well-tolerated in the acute treatment of migraine.Topics: Humans; Double-Blind Method; Drug Therapy, Combination; Headache; Migraine Disorders; Naproxen; Quality of Life; Sodium; Sumatriptan; Tryptamines
PubMed: 37782065
DOI: 10.18071/isz.76.0293 -
The Journal of the American Osteopathic... Jan 2019Autism spectrum disorder (ASD) is a neurodevelopmental condition associated with difficulties in the social, communicative, and behavioral domains. Most cases of ASD... (Review)
Review
Autism spectrum disorder (ASD) is a neurodevelopmental condition associated with difficulties in the social, communicative, and behavioral domains. Most cases of ASD arise from an unknown etiologic process, but there are numerous risk factors, including comorbidities and maternal exposures. Although it is not part of the diagnostic criteria, hearing difficulties ranging from deafness to hyperacusis are present in the majority of persons with ASD. High-functioning children with ASD have been found to have significantly slower and asymmetric auditory brainstem reflexes. Additionally, histopathological studies of postmortem brainstems in decedents who had ASD have consistently revealed significantly fewer neurons in auditory nuclei compared with those in people who did not have ASD. The authors review the literature implicating auditory dysfunction in ASD along with results from human study participants and postmortem human brain tissue. Together, these results implicate significant structural and functional abnormalities in the auditory brainstem in ASD and support the utility of auditory testing to screen for ASD.
Topics: Auditory Cortex; Autism Spectrum Disorder; Brain Stem; Hearing Disorders; Humans
PubMed: 30615041
DOI: 10.7556/jaoa.2019.007 -
Otolaryngologic Clinics of North America Aug 2020Tinnitus is commonly experienced by military Service Members and Veterans, especially by the newest generation who served in Iraq and Afghanistan. When patients seek... (Review)
Review
Tinnitus is commonly experienced by military Service Members and Veterans, especially by the newest generation who served in Iraq and Afghanistan. When patients seek health care for tinnitus, it is important to determine its type, check for comorbid conditions that might be triggering or exacerbating the condition, and to address its functional and psychosocial effects. Otolaryngologists are usually the first health care professional to evaluate a patient with tinnitus, and it is essential to provide appropriate referrals for this high-burden condition. Noise-induced tinnitus is multifaceted; by performing a thorough assessment, appropriate action can be taken to best meet the needs of patients.
Topics: Afghan Campaign 2001-; Hearing Loss, Noise-Induced; Humans; Hyperacusis; Iraq War, 2003-2011; Military Personnel; Noise; Ototoxicity; Practice Guidelines as Topic; Quality of Life; Risk Factors; Tinnitus; United States
PubMed: 32334867
DOI: 10.1016/j.otc.2020.03.004 -
Journal of the Association For Research... Dec 2023Tinnitus would benefit from an objective biomarker. The goal of this study is to identify plasma biomarkers of constant and chronic tinnitus among selected circulating... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
Tinnitus would benefit from an objective biomarker. The goal of this study is to identify plasma biomarkers of constant and chronic tinnitus among selected circulating inflammatory proteins.
METHODS
A case-control retrospective study on 548 cases with constant tinnitus and 548 matched controls from the Swedish Tinnitus Outreach Project (STOP), whose plasma samples were examined using Olink's Inflammatory panel. Replication and meta-analysis were performed using the same method on samples from the TwinsUK cohort. Participants from LifeGene, whose blood was collected in Stockholm and Umeå, were recruited to STOP for a tinnitus subtyping study. An age and sex matching was performed at the individual level. TwinsUK participants (n = 928) were selected based on self-reported tinnitus status over 2 to 10 years. Primary outcomes include normalized levels for 96 circulating proteins, which were used as an index test. No reference standard was available in this study.
RESULTS
After adjustment for age, sex, BMI, smoking, hearing loss, and laboratory site, the top proteins identified were FGF-21, MCP4, GDNF, CXCL9, and MCP-1; however, these were no longer statistically significant after correction for multiple testing. Stratification by sex did not yield any significant associations. Similarly, associations with hearing loss or other tinnitus-related comorbidities such as stress, anxiety, depression, hyperacusis, temporomandibular joint disorders, and headache did not yield any significant associations. Analysis in the TwinsUK failed in replicating the top candidates. Meta-analysis of STOP and TwinsUK did not reveal any significant association. Using elastic net regularization, models exhibited poor predictive capacity tinnitus based on inflammatory markers [sensitivity = 0.52 (95% CI 0.47-0.57), specificity = 0.53 (0.48-0.58), positive predictive value = 0.52 (0.47-0.56), negative predictive values = 0.53 (0.49-0.58), and AUC = 0.53 (0.49-0.56)].
DISCUSSION
Our results did not identify significant associations of the selected inflammatory proteins with constant tinnitus. Future studies examining longitudinal relations among those with more severe tinnitus and using more recent expanded proteomics platforms and sampling of cerebrospinal fluid could increase the likelihood of identifying relevant molecular biomarkers.
Topics: Humans; Tinnitus; Retrospective Studies; Hearing Loss; Hyperacusis; Biomarkers
PubMed: 38079022
DOI: 10.1007/s10162-023-00920-3