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Journal of Clinical Medicine Jan 2024To investigate whether the incidence of triggers, prodromal symptoms, hypersensitivity symptoms accompanying headache and responses to triptans were modified during a...
Nine-Month Continuous Fremanezumab Prophylaxis on the Response to Triptans and Also on the Incidence of Triggers, Hypersensitivity and Prodromal Symptoms of Patients with High-Frequency Episodic Migraine.
To investigate whether the incidence of triggers, prodromal symptoms, hypersensitivity symptoms accompanying headache and responses to triptans were modified during a continuous 9-month fremanezumab therapy for migraine prophylaxis. We studied 63 patients with high-frequency episodic migraine (HFEM). Enrolled patients received fremanezumab for nine consecutive months before defining the response rates and being stratified into treatment responders (≥50-74% reduction in monthly headache days (MHDs)), super responders (≥75%), partial non-responders (<50%) and super non-responders (<30%). Through headache diaries, patients provided data in order to document the impact of fremanezumab on the incidence of triggers, associated symptoms followed by headache and response to triptans (the use of the migraine treatment optimization questionnaire-4 (mTOQ-4)) during the 9-month treatment period. Fremanezumab had early (after 3 monthly cycles) beneficial effects on the response to triptans in the majority of responders with relevant increases in mTOQ-4 scoring, but also in half of partial non-responders. A significant reduction in median days with migraine-associated symptoms was seen in responders after 6 months of therapy with fremanezumab, mostly for osmophobia, photophobia, phonophobia and nausea/vomiting, but partial non-responders also benefited. Likewise, the incidence of self-reported prodromal symptoms was significantly reduced in responders and was modestly diminished in partial non-responders. Triggers remained unaffected in both responders and non-responders. Fremanezumab given for at least 6-9 months may exert neuromodulatory effects in the migraine brain. These effects could result both in the inhibition of migraine chronification, but also in the diminishing of the magnitude of migraine-associated symptoms, mostly in responders and in partial non-responders.
PubMed: 38256516
DOI: 10.3390/jcm13020386 -
Medicina (Kaunas, Lithuania) Jan 2024The study of migraine is based on the complexity of the pathology, both at the pathophysiological and epidemiological levels. Although it affects more than a billion... (Review)
Review
The study of migraine is based on the complexity of the pathology, both at the pathophysiological and epidemiological levels. Although it affects more than a billion people worldwide, it is often underestimated and underreported by patients. Migraine must not be confused with a simple headache; it is a serious and disabling disease that causes considerable limitations in the daily life of afflicted people, including social, work, and emotional effects. Therefore, it causes a daily state of suffering and discomfort. It is important to point out that this pathology not only has a decisive impact on the quality of life of those who suffer from it but also on their families and, more generally, on society as a whole. The clinical picture of migraine is complex, with debilitating unilateral or bilateral head pain, and is often associated with characteristic symptoms such as nausea, vomiting, photophobia, and phonophobia. Hormonal, environmental, psychological, dietary, or other factors can trigger it. The present review focuses on the analysis of the physiopathological and pharmacological aspects of migraine, up to the correct dietary approach, with specific nutritional interventions aimed at modulating the symptoms. Based on the symptoms that the patient experiences, targeted and specific therapy is chosen to reduce the frequency and severity of migraine attacks. Specifically, the role of calcitonin gene-related peptide (CGRP) in the pathogenesis of migraine is analyzed, along with the drugs that effectively target the corresponding receptor. Particularly, CGRP receptor antagonists (gepants) are very effective drugs in the treatment of migraine, given their high diffusion in the brain. Moreover, following a ketogenic diet for only one or two months has been demonstrated to reduce migraine attacks. In this review, we highlight the diverse facets of migraine, from its physiopathological and pharmacological aspects to prevention and therapy.
Topics: Humans; Calcitonin Gene-Related Peptide; Diet, Ketogenic; Headache; Migraine Disorders; Quality of Life; Calcitonin Gene-Related Peptide Receptor Antagonists
PubMed: 38256423
DOI: 10.3390/medicina60010163 -
International Journal of Clinical... Apr 2024Teprotumumab was approved by the US Food and Drug Administration (FDA) for the treatment of thyroid eye disease in 2020. However, its adverse events (AEs) have not been...
BACKGROUND
Teprotumumab was approved by the US Food and Drug Administration (FDA) for the treatment of thyroid eye disease in 2020. However, its adverse events (AEs) have not been investigated in real-world settings.
AIM
This study aimed to detect and evaluate AEs associated with teprotumumab in the real-world setting by conducting a pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) database.
METHOD
Reporting odds ratio (ROR) was used to detect risk signals from the data from January 2020 to March 2023 in the FAERS database.
RESULTS
A total of 3,707,269 cases were retrieved, of which 1542 were related to teprotumumab. The FAERS analysis identified 99 teprotumumab-related AE signals in 14 System Organ Classes (SOCs). The most frequent AEs were muscle spasms (n = 287), fatigue (n = 174), blood glucose increase (n = 121), alopecia (n = 120), nausea (n = 118), hyperacusis (n = 117), and headache (n = 117). The AEs with strongest signal strengths were autophony (ROR = 14,475.49), deafness permanent (ROR = 1853.35), gingival recession (ROR = 190.74), deafness neurosensory (ROR = 129.89), nail growth abnormal (ROR = 103.67), onychoclasis (ROR = 73.58), ear discomfort (ROR = 72.88), and deafness bilateral (ROR = 62.46). Eleven positive AE signals were found at the standardized MedDRA queries (SMQs) level, of which the top five SMQs were hyperglycemia/new-onset diabetes mellitus, hearing impairment, gastrointestinal nonspecific symptoms and therapeutic procedures, noninfectious diarrhea, and hypertension. Age significantly increased the risk of hearing impairment.
CONCLUSION
This study identified potential new and unexpected AE signals of teprotumumab. Our findings emphasize the importance of pharmacovigilance analysis in the real world to identify and manage AEs effectively, ultimately improving patient safety during teprotumumab treatment.
Topics: United States; Humans; United States Food and Drug Administration; Drug-Related Side Effects and Adverse Reactions; Data Mining; Pharmacovigilance; Adverse Drug Reaction Reporting Systems; Hearing Loss; Antibodies, Monoclonal, Humanized
PubMed: 38245664
DOI: 10.1007/s11096-023-01676-9 -
Frontiers in Neuroscience 2023The ongoing controversies about the neural basis of tinnitus, whether linked with central neural gain or not, may hamper efforts to develop therapies. We asked to what...
Differential cortical activation patterns: pioneering sub-classification of tinnitus with and without hyperacusis by combining audiometry, gamma oscillations, and hemodynamics.
The ongoing controversies about the neural basis of tinnitus, whether linked with central neural gain or not, may hamper efforts to develop therapies. We asked to what extent measurable audiometric characteristics of tinnitus without (T) or with co-occurrence of hyperacusis (TH) are distinguishable on the level of cortical responses. To accomplish this, electroencephalography (EEG) and concurrent functional near-infrared spectroscopy (fNIRS) were measured while patients performed an attentionally demanding auditory discrimination task using stimuli within the individual tinnitus frequency (fTin) and a reference frequency (fRef). Resting-state-fMRI-based functional connectivity (rs-fMRI-bfc) in ascending auditory nuclei (AAN), the primary auditory cortex (AC-I), and four other regions relevant for directing attention or regulating distress in temporal, parietal, and prefrontal cortex was compiled and compared to EEG and concurrent fNIRS activity in the same brain areas. We observed no group differences in pure-tone audiometry (PTA) between 10 and 16 kHz. However, the PTA threshold around the tinnitus pitch was positively correlated with the self-rated tinnitus loudness and also correlated with distress in T-groups, while TH experienced their tinnitus loudness at minimal loudness levels already with maximal suffering scores. The T-group exhibited prolonged auditory brain stem (ABR) wave I latency and reduced ABR wave V amplitudes (indicating reduced neural synchrony in the brainstem), which were associated with lower rs-fMRI-bfc between AAN and the AC-I, as observed in previous studies. In T-subjects, these features were linked with elevated spontaneous and reduced evoked gamma oscillations and with reduced deoxygenated hemoglobin (deoxy-Hb) concentrations in response to stimulation with lower frequencies in temporal cortex (Brodmann area (BA) 41, 42, 22), implying less synchronous auditory responses during active auditory discrimination of reference frequencies. In contrast, in the TH-group gamma oscillations and hemodynamic responses in temporoparietal regions were reversed during active discrimination of tinnitus frequencies. Our findings suggest that T and TH differ in auditory discrimination and memory-dependent directed attention during active discrimination at either tinnitus or reference frequencies, offering a test paradigm that may allow for more precise sub-classification of tinnitus and future improved treatment approaches.
PubMed: 38239827
DOI: 10.3389/fnins.2023.1232446 -
Journal of the Association For Research... Apr 2024Tinnitus subtypes are proposed to lie on a continuum of different symptom dimensions rather than be categorical. However, there is no comprehensive empirical data... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
Tinnitus subtypes are proposed to lie on a continuum of different symptom dimensions rather than be categorical. However, there is no comprehensive empirical data showing this complex relationship between different tinnitus symptoms. The objective of this study is to provide empirical evidence for the dimensional nature of tinnitus and how different auditory and non-auditory symptoms interact with each other through complex interactions. We do this using graph theory, a mathematical tool that empirically maps this complex interaction. This way, graph theory can be utilised to highlight a new and possibly important outlook on how we can understand the heterogeneous nature of tinnitus.
DESIGN
In the current study, we use the screening databases of the Treatment Evaluation of Neuromodulation for Tinnitus-Stage A1 (TENT-A1) and A2 (TENT-A2) randomised trials to delineate the dimensional relationship between different clinical measures of tinnitus as a secondary data analysis. We first calculate the empirical relationship by computing the partial correlation. Following this, we use different measures of centrality to describe the contribution of different clinical measures to the overall network. We also calculate the stability of the network and compare the similarity and differences between TENT-A1 and TENT-A2.
RESULTS
Components of the auditory subnetwork (loudness discomfort level, sound sensitivity, average hearing loss and high frequency hearing loss) are highly inter-connected in both networks with sound sensitivity and loudness discomfort level being highly influential with high measures of centrality. Furthermore, the relationship between the densely connected auditory subnetwork with tinnitus-related distress seems to vary at different levels of distress, hearing loss, duration and age of the participants.
CONCLUSION
Our findings provide first-time evidence for tinnitus varying in a dimensional fashion illustrating the heterogeneity of this phantom percept and its ability to be perceptually integrated, yet behaviourally segregated on different symptomatic dimensions.
Topics: Humans; Tinnitus; Hearing Loss; Acoustic Stimulation; Deafness
PubMed: 38238526
DOI: 10.1007/s10162-023-00923-0 -
Clinical Neurology and Neurosurgery Jan 2024Other primary headache disorders (OPHD) are under-investigated compared to frequent primary headache types like migraine, tension-type headache, and trigeminal autonomic...
OBJECTIVE
Other primary headache disorders (OPHD) are under-investigated compared to frequent primary headache types like migraine, tension-type headache, and trigeminal autonomic cephalalgias. Knowledge of the distribution and characteristics of OPHD subtypes is crucial for their recognition. We aimed to determine the prevalence at the hospital and headache clinics and clinical characteristics of OPHDs in patients from 13 countries.
METHODS
We analyzed a large dataset from the cross-sectional study Head-MENA-A (Middle East, North Africa, Asia). Consecutive patients over 10 years of age presenting with headaches were included from outpatient, inpatient, and emergency settings. A structured questionnaire addressing demographics, headache characteristics, accompanying symptoms, and triggers was administered. Headache subtypes were diagnosed according to the ICHD-3 criteria.
RESULTS
Among patients complaining of headaches (n = 3722), 106 (2.9%) were diagnosed with OPHD. Fifty-two patients (1.4% of all headache patients) had only OPHD, while 54 (1.5%) had both OPHD and a co-existing primary headache (mostly migraine). All OPHDs were more common in females. The most frequent subtypes were new daily persistent headache and primary stabbing headache (0.2% each among all admitted patients). Photophobia and phonophobia were the most frequent accompanying symptoms, while physical activity (28.8%), stress (15.4%), and the Valsalva maneuver (15.4%) were the most common triggering factors. The majority of triggering factors were more pronounced in patients with both migraine and OPHD.
CONCLUSIONS
Other primary headaches are rare and heterogeneous. Their high co-existence with migraine suggests shared predisposing factors, hinting at a "headache continuum" concept for primary headaches.
Topics: Female; Humans; Cross-Sectional Studies; Headache; Migraine Disorders; Headache Disorders; Asia; Africa; Middle East; Headache Disorders, Primary
PubMed: 38232607
DOI: 10.1016/j.clineuro.2023.108112 -
The American Journal of Case Reports Jan 2024BACKGROUND Superior ophthalmic vein thrombosis (SOVT) is a rare condition, with an incidence of 3 to 4 cases per million per year. SOVT can be classified according to...
BACKGROUND Superior ophthalmic vein thrombosis (SOVT) is a rare condition, with an incidence of 3 to 4 cases per million per year. SOVT can be classified according to the underlying etiology into septic or aseptic SOVT. We present a case of right SOVT in a previously healthy patient with a positive blood culture of methicillin-resistant Staphylococcus aureus (MRSA). CASE REPORT A previously healthy 38-year-old female patient presented with a 2-week history of worsening right-sided headache associated with photophobia, phonophobia, right-sided ear pain, and tinnitus. The best corrected visual acuity was 6/12 in the right eye and 6/6 in the left eye. Ophthalmic examination revealed right eye upper lid edema, proptosis, and diplopia in all gazes, mainly vertical. The fundus examination showed a raised hyperemic right optic disc with blurred margins. Laboratory investigations showed a positive blood culture of MRSA and elevated levels of inflammatory markers erythrocyte sedimentation rate and C-reactive protein. Orbital computed tomography examination showed periorbital and orbital cellulitis with superior ophthalmic vein thrombosis. The patient was treated successfully with antibiotics and anticoagulants. At 1-month follow-up, the patient was compliant with medications and reported full resolution of symptoms, with no visual acuity impairment. CONCLUSIONS SOVT is a challenging ophthalmic condition and can be present concurrent with orbital cellulitis or cavernous sinus thrombosis. Early imaging studies and proper management are important to prevent serious complications. Ophthalmologists need to be alerted of the importance of tailoring antibiotics based on the causative agent, to decrease the risk of therapeutic failure and microbial resistance.
Topics: Female; Humans; Adult; Orbital Cellulitis; Methicillin-Resistant Staphylococcus aureus; Venous Thrombosis; Eye; Anti-Bacterial Agents
PubMed: 38225808
DOI: 10.12659/AJCR.941886 -
Journal of Neurophysiology Feb 2024Exposure to intense noise environments is a major cause of sensorineural hearing loss and auditory perception disorders, such as tinnitus and hyperacusis, which may have...
Exposure to intense noise environments is a major cause of sensorineural hearing loss and auditory perception disorders, such as tinnitus and hyperacusis, which may have a central origin. The effects of noise-induced hearing loss on the auditory cortex have been documented in many studies. One limitation of these studies, however, is that the effects of noise trauma have been mostly studied at the granular layer (i.e, the main cortical recipient of thalamic input), while the cortex is a very complex structure, with six different layers each having its own pattern of connectivity and role in sensory processing. The present study aims to investigate the effects of acute and chronic noise trauma on the laminar pattern of stimulus-evoked activity in the primary auditory cortex of the anesthetized guinea pig. We show that acute and chronic noise trauma are both followed by an increase in stimulus-evoked cortical responses, mostly in the granular and supragranular layers. The cortical responses are more monotonic as a function of the intensity level after noise trauma. There was minimal change, if any, in local field potential (LFP) amplitude after acute noise trauma, while LFP amplitude was enhanced after chronic noise trauma. Finally, LFP and the current source density analysis suggest that acute but more specifically chronic noise trauma is associated with the emergence of a new sink in the supragranular layer. This result suggests that supragranular layers become a major input recipient. We discuss the possible mechanisms and functional implications of these changes. Our study shows that cortical activity is enhanced after trauma and that the sequence of cortical column activation during stimulus-evoked response is altered, i.e. the supragranular layer becomes a major input recipient. We speculate that these large cortical changes may play a key role in the auditory hypersensitivity (hyperacusis) that can be triggered after noise trauma in human subjects.
Topics: Humans; Animals; Guinea Pigs; Auditory Cortex; Acoustic Stimulation; Hyperacusis; Noise; Hearing Loss, Noise-Induced; Tinnitus; Evoked Potentials, Auditory
PubMed: 38198658
DOI: 10.1152/jn.00427.2022 -
BioRxiv : the Preprint Server For... Jan 2024Sound is jointly processed along acoustic and emotional dimensions. These dimensions can become distorted and entangled in persons with sensory disorders, producing a...
Sound is jointly processed along acoustic and emotional dimensions. These dimensions can become distorted and entangled in persons with sensory disorders, producing a spectrum of loudness hypersensitivity, phantom percepts, and - in some cases - debilitating sound aversion. Here, we looked for objective signatures of disordered hearing (DH) in the human face. Pupil dilations and micro facial movement amplitudes scaled with sound valence in neurotypical listeners but not DH participants with chronic tinnitus (phantom ringing) and sound sensitivity. In DH participants, emotionally evocative sounds elicited abnormally large pupil dilations but blunted and invariant facial reactions that jointly provided an accurate prediction of individual tinnitus and hyperacusis questionnaire handicap scores. By contrast, EEG measures of central auditory gain identified steeper neural response growth functions but no association with symptom severity. These findings highlight dysregulated affective sound processing in persons with bothersome tinnitus and sound sensitivity disorders and introduce approaches for their objective measurement.
PubMed: 38187580
DOI: 10.1101/2023.12.22.571929 -
Journal of Child Neurology Jan 2024Current criteria help differentiate cluster headache from migraine. However, children may have overlapping features making it difficult to distinguish the 2 conditions,...
BACKGROUND
Current criteria help differentiate cluster headache from migraine. However, children may have overlapping features making it difficult to distinguish the 2 conditions, which may delay diagnosis. Differentiating cluster headache from migraine is important regarding treatment as well as diagnostic workup of secondary headache etiologies.
METHODS
Cases at a single pediatric children's hospital from 2015 to 2023 diagnosed with cluster headache before the age of 18 years were reviewed.
RESULTS
Twenty-five cases were identified of which 22 cases met criteria for either chronic, episodic, or probable cluster headache. Three cases were diagnosed with cluster headache by their provider, but documentation was insufficient to meet criteria for cluster headache. There were 16 females and 9 males between ages 6 and 17 years. Five cases were identified as symptomatic, 2 cases as chronic, 7 cases as episodic, and 13 cases as probable cluster headache. Symptomatic etiologies include Graves disease, optic neuritis, prolactinoma, hypothalamic pilocytic astrocytoma with carotid stenosis, and congenital right eye blindness. Migrainous features were common, including 76% with nausea, 36% with vomiting, 68% with photophobia, and 56% with phonophobia. Patients with cluster headache also had an independent diagnosis of migraine in 64%.
CONCLUSION
Children with cluster headache have a high frequency of migrainous symptoms and co-occurrent diagnosis of migraine. A careful history may differentiate cluster headache from migraine and treated accordingly. Children with cluster headache features should undergo screening for secondary causes with appropriate imaging and other studies. Except for prolactinoma, the symptomatic associations noted in this case series have not been reported before.
Topics: Humans; Cluster Headache; Male; Female; Child; Adolescent; Migraine Disorders; Diagnosis, Differential; Retrospective Studies
PubMed: 38146171
DOI: 10.1177/08830738231220415