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Neurology Oct 2021Endogenous and exogenous female sex hormones are considered important contributors to migraine pathophysiology. Previous studies have cautiously suggested that... (Comparative Study)
Comparative Study
BACKGROUND AND OBJECTIVES
Endogenous and exogenous female sex hormones are considered important contributors to migraine pathophysiology. Previous studies have cautiously suggested that perimenstrual migraine attacks have a longer duration and are associated with higher disability compared to nonperimenstrual attacks, but they showed conflicting results on acute therapy efficacy, pain intensity, and associated symptoms. We compared perimenstrual and nonperimenstrual migraine attack characteristics and assessed premenstrual syndrome (PMS) in women with migraine.
METHODS
Women with migraine were invited to complete a headache e-diary. Characteristics of perimenstrual attacks and nonperimenstrual attacks were compared. The primary outcome was attack duration. Secondary outcomes were headache intensity, accompanying symptoms, acute medication intake, and pain coping. Mixed effects models were used to account for multiple attacks within patients. PMS was assessed in patients without hormonal contraceptives. Subgroup analyses were performed for women with menstrually related migraine (MRM) and nonmenstrually related migraine (non-MRM) and women with a natural menstrual cycle and women using hormonal contraceptives.
RESULTS
A representative group of 500 participants completed the e-diary for at least 1 month. Perimenstrual migraine attacks (n = 998) compared with nonperimenstrual attacks (n = 4097) were associated with longer duration (20.0 vs 16.1 hours, 95% confidence interval 0.2-0.4), higher recurrence risk (odds ratio [OR] 2.4 [2.0-2.9]), increased triptan intake (OR 1.2 [1.1-1.4]), higher headache intensity (OR 1.4 [1.2-1.7]), less pain coping (mean difference -0.2 [-0.3 to -0.1]), more pronounced photophobia (OR 1.3 [1.2-1.4]) and phonophobia (OR 1.2 [1.1-1.4]), and less aura (OR 0.8 [0.6-1.0]). In total, 396/500 women completed the diary for ≥3 consecutive menstrual cycles, of whom 56% (221/396) fulfilled MRM criteria. Differences in attack characteristics became more pronounced when focusing on women with MRM and women using hormonal contraceptives. Prevalence of PMS was not different for women with MRM compared to non-MRM (11% vs 15%).
DISCUSSION
The longer duration of perimenstrual migraine attacks in women (with MRM) is associated with higher recurrence risk and increased triptan use. This may increase the risk of medication overuse and emphasizes the need to develop female-specific prophylactic treatment.
Topics: Adult; Female; Humans; Medical Records; Menstruation; Middle Aged; Migraine Disorders; Prevalence; Tryptamines
PubMed: 34493613
DOI: 10.1212/WNL.0000000000012723 -
International Journal of Environmental... Jun 2022Misophonia is a scarcely known disorder. This systematic review (1) offers a quantitative and qualitative analysis of the literature since 2001, (2) identifies the most... (Review)
Review
Misophonia is a scarcely known disorder. This systematic review (1) offers a quantitative and qualitative analysis of the literature since 2001, (2) identifies the most relevant aspects but also controversies, (3) identifies the theoretical and methodological approaches, and (4) highlights the outstanding advances until May 2022 as well as aspects that remain unknown and deserve future research efforts. Misophonia is characterized by strong physiological, emotional, and behavioral reactions to auditory, visual, and/or kinesthetic stimuli of different nature regardless of their physical characteristics. These misophonic responses include anger, general discomfort, disgust, anxiety, and avoidance and escape behaviors, and decrease the quality of life of the people with the disorder and their relatives. There is no consensus on the diagnostic criteria yet. High comorbidity between misophonia and other psychiatric and auditory disorders is reported. Importantly, the confusion with other disorders contributes to its underdiagnosis. In recent years, assessment systems with good psychometric properties have increased considerably, as have treatment proposals. Although misophonia is not yet included in international classification systems, it is an emerging field of growing scientific and clinical interest.
Topics: Anger; Anxiety Disorders; Emotions; Humans; Hyperacusis; Quality of Life
PubMed: 35682372
DOI: 10.3390/ijerph19116790 -
The Journal of International Advanced... Apr 2020Air-bone gaps (ABGs) are commonly found in patients with conductive or mixed hearing loss generally due to outer- and/or middle-ear diseases such as otitis externa,... (Review)
Review
Air-bone gaps (ABGs) are commonly found in patients with conductive or mixed hearing loss generally due to outer- and/or middle-ear diseases such as otitis externa, tympanic membrane perforation, interruption or fixation of the ossicular chain, and chronic suppurative otitis media. ABGs can also be found in correlation with inner-ear disorders, such as endolymphatic hydrops, enlarged vestibular aqueduct syndrome, semicircular canal dehiscence, gusher syndrome, cochlear dehiscence, and Paget disease's as well cerebral vascular anomalies including dural arteriovenous fistula. The typical clinical presentation of inner-ear conditions or cerebral vascular anomalies causing ABGs includes audiological and vestibular symptoms like vertigo, oscillopsia, dizziness, imbalance, spinning sensation, pulsatile or continuous tinnitus, hyperacusis, autophony, auricular fullness, Tullio's phenomenon, and Hennebert's sign. Establishing a definitive diagnosis of the underlying condition in patients presenting with an ABG is often challenging to do and, in many patients, the condition may remain undefined. Results from an accurate clinical, audiological, and vestibular evaluation can be suggestive for the underlying condition; however, radiological assessment by computed tomography and/or magnetic resonance imaging is mandatory to confirm any diagnostic suspicion. In this review, we describe and discuss the most recent updates available regarding the clinical presentation and diagnostic workup of inner-ear conditions that may present together with ABGs.
Topics: Air; Bone Conduction; Bone and Bones; Central Nervous System Vascular Malformations; Child; Cochlea; Ear Ossicles; Endolymphatic Hydrops; Female; Hearing Loss; Hearing Loss, Conductive; Hearing Loss, Mixed Conductive-Sensorineural; Hearing Loss, Sensorineural; Humans; Labyrinth Diseases; Magnetic Resonance Imaging; Male; Meniere Disease; Middle Aged; Osteitis Deformans; Semicircular Canal Dehiscence; Tomography, X-Ray Computed; Vestibular Aqueduct
PubMed: 32401207
DOI: 10.5152/iao.2020.7764 -
Frontiers in Neuroscience 2022
PubMed: 36685217
DOI: 10.3389/fnins.2022.1077097 -
The Journal of Neuroscience : the... Oct 2022Dysfunction of the peripheral auditory nerve (AN) contributes to dynamic changes throughout the central auditory system, resulting in abnormal auditory processing,...
Dysfunction of the peripheral auditory nerve (AN) contributes to dynamic changes throughout the central auditory system, resulting in abnormal auditory processing, including hypersensitivity. Altered sound sensitivity is frequently observed in autism spectrum disorder (ASD), suggesting that AN deficits and changes in auditory information processing may contribute to ASD-associated symptoms, including social communication deficits and hyperacusis. The MEF2C transcription factor is associated with risk for several neurodevelopmental disorders, and mutations or deletions of produce a haploinsufficiency syndrome characterized by ASD, language, and cognitive deficits. A mouse model of this syndromic ASD (-Het) recapitulates many of the haploinsufficiency syndrome-linked behaviors, including communication deficits. We show here that -Het mice of both sexes exhibit functional impairment of the peripheral AN and a modest reduction in hearing sensitivity. We find that MEF2C is expressed during development in multiple AN and cochlear cell types; and in -Het mice, we observe multiple cellular and molecular alterations associated with the AN, including abnormal myelination, neuronal degeneration, neuronal mitochondria dysfunction, and increased macrophage activation and cochlear inflammation. These results reveal the importance of MEF2C function in inner ear development and function and the engagement of immune cells and other non-neuronal cells, which suggests that microglia/macrophages and other non-neuronal cells might contribute, directly or indirectly, to AN dysfunction and ASD-related phenotypes. Finally, our study establishes a comprehensive approach for characterizing AN function at the physiological, cellular, and molecular levels in mice, which can be applied to animal models with a wide range of human auditory processing impairments. This is the first report of peripheral auditory nerve (AN) impairment in a mouse model of human haploinsufficiency syndrome that has well-characterized ASD-related behaviors, including communication deficits, hyperactivity, repetitive behavior, and social deficits. We identify multiple underlying cellular, subcellular, and molecular abnormalities that may contribute to peripheral AN impairment. Our findings also highlight the important roles of immune cells (e.g., cochlear macrophages) and other non-neuronal elements (e.g., glial cells and cells in the stria vascularis) in auditory impairment in ASD. The methodological significance of the study is the establishment of a comprehensive approach for evaluating peripheral AN function and impact of peripheral AN deficits with minimal hearing loss.
Topics: Male; Female; Mice; Animals; Humans; Autistic Disorder; Autism Spectrum Disorder; MEF2 Transcription Factors; Cochlear Nerve; Disease Models, Animal
PubMed: 36180228
DOI: 10.1523/JNEUROSCI.0253-22.2022 -
American Journal of Audiology Oct 2021Purpose Tinnitus and hyperacusis are debilitating conditions often associated with age-, noise-, and drug-induced hearing loss. Because of their subjective nature, the... (Review)
Review
Purpose Tinnitus and hyperacusis are debilitating conditions often associated with age-, noise-, and drug-induced hearing loss. Because of their subjective nature, the neural mechanisms that give rise to tinnitus and hyperacusis are poorly understood. Over the past few decades, considerable progress has been made in deciphering the biological bases for these disorders using animal models. Method Important advances in understanding the biological bases of tinnitus and hyperacusis have come from studies in which tinnitus and hyperacusis are consistently induced with a high dose of salicylate, the active ingredient in aspirin. Results Salicylate induced a transient hearing loss characterized by a reduction in otoacoustic emissions, a moderate cochlear threshold shift, and a large reduction in the neural output of the cochlea. As the weak cochlear neural signals were relayed up the auditory pathway, they were progressively amplified so that the suprathreshold neural responses in the auditory cortex were much larger than normal. Excessive central gain (neural amplification), presumably resulting from diminished inhibition, is believed to contribute to hyperacusis and tinnitus. Salicylate also increased corticosterone stress hormone levels. Functional imaging studies indicated that salicylate increased spontaneous activity and enhanced functional connectivity between structures in the central auditory pathway and regions of the brain associated with arousal (reticular formation), emotion (amygdala), memory/spatial navigation (hippocampus), motor planning (cerebellum), and motor control (caudate/putamen). Conclusion These results suggest that tinnitus and hyperacusis arise from aberrant neural signaling in a complex neural network that includes both auditory and nonauditory structures.
Topics: Animals; Auditory Cortex; Auditory Pathways; Humans; Hyperacusis; Ototoxicity; Tinnitus
PubMed: 33465315
DOI: 10.1044/2020_AJA-20-00023 -
Cephalalgia : An International Journal... Dec 2020For future experimental studies or the development of targeted pharmaceutical agents, a deeper insight into the pathophysiology of migraine is of utmost interest....
BACKGROUND
For future experimental studies or the development of targeted pharmaceutical agents, a deeper insight into the pathophysiology of migraine is of utmost interest. Reliable methods to trigger migraine attacks including aura are desirable to study this complex disease .
METHODS
To investigate hypoxia as a trigger for migraine and aura, we exposed volunteers diagnosed with migraine, with (n = 16) and without aura (n = 14), to hypoxia utilizing a hypoxic chamber adjusted to a FiO of 12.6%. The occurrence of headache, migraine, aura, and accompanying symptoms were registered and vital signs were collected for 6 hours under hypoxia and 2 hours of follow-up. A binary logistic regression analysis examined the probability of triggering headaches, migraines, aura, photo- and phonophobia.
FINDINGS
Of 30 participants, 24 (80.0%) developed headaches and 19 (63.3%) migraine, five (16.7%) reported aura. Two patients that developed aura never experienced aura symptoms before in their life. The increase of mean heart frequency was higher in patients developing headaches or migraine. Mean SpO during hypoxia was 83.39%.
CONCLUSION
Hypoxia was able to trigger migraine attacks and aura independently of any pharmacological agent.
Topics: Epilepsy; Headache; Humans; Hypoxia; Migraine Disorders; Migraine with Aura
PubMed: 32791920
DOI: 10.1177/0333102420949202 -
FASEB Journal : Official Publication of... Mar 2020Autism spectrum disorders (ASD) are strongly associated with auditory hypersensitivity or hyperacusis (difficulty tolerating sounds). Fragile X syndrome (FXS), the most... (Review)
Review
Autism spectrum disorders (ASD) are strongly associated with auditory hypersensitivity or hyperacusis (difficulty tolerating sounds). Fragile X syndrome (FXS), the most common monogenetic cause of ASD, has emerged as a powerful gateway for exploring underlying mechanisms of hyperacusis and auditory dysfunction in ASD. This review discusses examples of disruption of the auditory pathways in FXS at molecular, synaptic, and circuit levels in animal models as well as in FXS individuals. These examples highlight the involvement of multiple mechanisms, from aberrant synaptic development and ion channel deregulation of auditory brainstem circuits, to impaired neuronal plasticity and network hyperexcitability in the auditory cortex. Though a relatively new area of research, recent discoveries have increased interest in auditory dysfunction and mechanisms underlying hyperacusis in this disorder. This rapidly growing body of data has yielded novel research directions addressing critical questions regarding the timing and possible outcomes of human therapies for auditory dysfunction in ASD.
Topics: Animals; Auditory Perception; Autism Spectrum Disorder; Fragile X Syndrome; Humans; Models, Biological
PubMed: 32039504
DOI: 10.1096/fj.201902435R -
Frontiers in Pain Research (Lausanne,... 2022This study aimed to assess the prevalence and clinical characteristics of headaches, in particular secondary headaches.
INTRODUCTION
This study aimed to assess the prevalence and clinical characteristics of headaches, in particular secondary headaches.
MATERIALS AND METHODS
This observational study was performed at the ASST Spedali Civili of Brescia, Italy. Visits to the Emergency Department (ED) and subsequent hospitalizations regarding a new or worsening headache in the 16 days following the administration of the COVID-19 vaccine between January 2021 and January 2022 were recorded and compared with those of January 2019-January 2020.
RESULTS
The ratio between ED admissions due to headaches and total ED admissions was significantly higher in 2021 compared with 2019 (4.84% vs. 4.27%; < 0.0001). Two-hundred and eighty-nine ED headache admissions (10.8% of all ED headache admissions) were time-correlated to the COVID-19 vaccination, of which 40 were hospitalized in order to exclude a symptomatic etiology. At discharge, 32 patients had a diagnosis of benign headache not attributed to any cranial/extracranial disorder and eight patients of secondary headache, whose diagnoses were the following: Headache attributed to cranial and/or cervical vascular disorder ( = 4); headache attributed to nonvascular intracranial disorder ( = 2); headache or facial pain attributed to disorder of the cranium, neck, eyes, ears, nose, sinuses, teeth, mouth, or other facial or cervical structure ( = 1); and painful lesions of the cranial nerves ( = 1). The headache most frequently reported by patients had migraine-like characteristics: the localization was predominantly frontal or temporal, the pain was described as throbbing and severe in intensity and it was frequently accompanied by nausea/vomit, and photo-phonophobia. Over half-regardless of the final diagnosis-of hospitalized patients had a history of primary headaches.
CONCLUSIONS
Following the spread of COVID-19 vaccination, the number of ED admissions due to headaches significantly increased. However, less than 14% of all the ED visits due to a headache time-correlated to the COVID-19 vaccination were actually hospitalized, with most patients documenting a benign headache, possibly related to the generic side effects of the vaccination. Only 8/40 hospitalized patients were diagnosed with a secondary headache. These benign headaches would actually fulfill diagnostic criteria for 8.1 Headaches attributed to the use of or exposure to a substance (ICHD-3), although, at the time being, it does not include vaccines as possible substances.The headache migraine-like characteristics' reported by most patients could suggest activation of the trigeminovascular pathway by all the cytokines and other pro-inflammatory molecules released following the vaccination.
PubMed: 36425358
DOI: 10.3389/fpain.2022.994140 -
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