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Cellular Signalling Jun 2024Calcitonin gene-related peptide (CGRP) and adrenomedullin 2/intermedin (AM2/IMD) play important roles in several pathologies, including cardiovascular disease, migraine...
Calcitonin gene-related peptide (CGRP) and adrenomedullin 2/intermedin (AM2/IMD) play important roles in several pathologies, including cardiovascular disease, migraine and cancer. The efficacy of drugs targeting CGRP signalling axis for the treatment of migraine patients is sometimes offset by side effects (e.g. inflammation and microvascular complications, including aberrant neovascularisation in the skin). Recent studies using animal models implicate CGRP in lymphangiogenesis and lymphatic vessel function. However, whether CGRP or AM2/IMD can act directly on lymphatic endothelial cells is unknown. Here, we found that CGRP and AM2/IMD induced p44/42 MAPK phosphorylation in a time- and dose-dependent manner in primary human dermal lymphatic endothelial cells (HDLEC) in vitro, and thus directly affected these cells. These new findings reveal CGRP and AM2/IMD as novel regulators of LEC biology and warrant further investigation of their roles in the context of pathologies associated with lymphatic function in the skin and other organs, and therapies targeting CGRP signalling axis.
PubMed: 38878805
DOI: 10.1016/j.cellsig.2024.111261 -
Turkish Neurosurgery Dec 2023To describe the relationship between aneurysm size and location and the prevalence of headache at diagnosis and three-and-six-month follow-up in a sample of patients...
AIM
To describe the relationship between aneurysm size and location and the prevalence of headache at diagnosis and three-and-six-month follow-up in a sample of patients with UIAs.
MATERIAL AND METHODS
In this cohort study, patients were diagnosed with UIAs by digital subtraction angiography. Follow-up visits occurred three and six months after the diagnosis. Headache presence was registered and further classified by phenotypes. After DSA, recorded variables were: aneurysm number, morphology, location, and size (diameter [W], neck [N], and dome-neck distance [H]). The aspect ratio (H/N) and the dome/neck ratio (W/N) were calculated. The outcome of this study was the self-reported headache status at follow-up.
RESULTS
Data from 42 patients and 46 aneurysms were available, 81.0% women, with a mean age of 57.4±14.3 years. Headache was reported by 61.9% of the patients. The pain phenotype was tension-type in 38.1%, migraine in 11.9%, neuralgia in 2.4%, and unclassifiable in 9.5%. The median (min-max) measurements were W=5.05 (0.89-22.9); N=3.02 (0.52-17.9); H=5.08 (0.92-23.0); aspect ratio 1.59 (0.68-17.69) and W/N ratio 1.65 (0.62-16.92). Thirty-three patients (37 aneurysms) received treatment, 47.8% by surgical clipping and 32.6% by endovascular occlusion. In treated patients, the headache persisted in 14.3% on the first and 9.5% on the second visit. There were no differences in any registered variables between patients with and without headaches at follow-up.
CONCLUSION
This study found data that supports that headache in patients with UIAs improves after treatment and that such improvement is probably unrelated to the size and shape of the UIAs.
PubMed: 38874253
DOI: 10.5137/1019-5149.JTN.45018-23.2 -
Frontiers in Immunology 2024[This corrects the article DOI: 10.3389/fimmu.2022.1075527.].
Corrigendum: Low rates of headache and migraine associated with intravenous immunoglobulin infusion using a 15-minute rate escalation protocol in 123 patients with primary immunodeficiency.
[This corrects the article DOI: 10.3389/fimmu.2022.1075527.].
PubMed: 38873596
DOI: 10.3389/fimmu.2024.1430313 -
Frontiers in Psychology 2024This study aimed to assess the association of anxiety, headache, and insomnia on the QoL of patients with long COVID-19.
PURPOSE
This study aimed to assess the association of anxiety, headache, and insomnia on the QoL of patients with long COVID-19.
METHODS
We conducted a cross-sectional survey between August 2020 and March 2023. A total of 200 participants were eligible, 53 were excluded and 147 patients with long COVID were included. QoL was evaluated across eight domains using the 36-Item Short Form Health Survey (SF-36). Standardized protocols including the Beck Anxiety Inventory (BAI) ( = 103), Pittsburgh Sleep Quality Index (PSQI) ( = 73), and Migraine Disability Assessment (MIDAS) ( = 67) were also used.
RESULTS
Participants with sleep disorders had significantly lower Vitality ( < 0.001). Participants with anxiety disorders had significantly lower Vitality ( = 0.001), poorer Mental Health ( = 0.008), and more severe Bodily Pain ( = 0.008). Participants with headache had significantly lower Vitality ( = 0.032), poorer Mental Health ( = 0.036), and poorer Physical Functioning ( = 0.016). Participants with both headache and anxiety had significantly lower Vitality ( = 0.005) and Mental Health ( = 0.043) domain scores. Correlation analysis revealed that higher scores for anxiety, sleep disorder, and headache were independently correlated with poorer QoL across various domains. The presence of sleep disorder was associated with a fourfold increase in risk of experiencing diminished Vitality (odds ratio [OR]4.47; 95% CI 1.01-19.69; = 0.048).
CONCLUSION
Participants with anxiety, sleep, and headache disorders tended to have a worse QoL. The Vitality and Mental Health domains were the most adversely affected in patients with long COVID. Sleep disorders were associated with a fourfold increase in the risk of poor Vitality.
PubMed: 38873510
DOI: 10.3389/fpsyg.2024.1394068 -
Four-Hour-Delayed Gadolinium 3D REAL IR and SPACE FLAIR MRI Correlated to Meniere Disease Histology.Ear, Nose, & Throat Journal Jun 2024This study aims to showcase the complementary nature of utilizing both histopathology and magnetic resonance imaging (MRI) in understanding the otologic pathophysiology...
This study aims to showcase the complementary nature of utilizing both histopathology and magnetic resonance imaging (MRI) in understanding the otologic pathophysiology of Meniere disease. In addition, it seeks to raise awareness of the value of preserving and curating historical temporal bone collections which continue to inform our understanding of otologic diseases. The essential anatomical feature of Meniere disease-the distended membranous labyrinth-is explored through a comparison of early temporal bone studies with contemporary MRI techniques. The histopathologic photomicrographs are of inner ear specimens from deceased patients with symptoms consistent with Meniere disease. The MRI sequences from living patients exhibiting classic Meniere disease symptoms during life are captured 4 hours post-administration of gadolinium. Both histopathologic examination and MRI imaging reveal consistent distention of the saccule, utricle, and scala media in patients with Meniere disease. The study shows the histologic photomicrographs of actual Meniere patients compared to the MRIs and successfully demonstrates the correlation between postmortem histological findings and MRI evidence of distension in living patients. A corresponding distension of the membranous labyrinth is seen in both the histologic specimens and the Meniere MRIs. This correlation suggests the potential utility of utilizing MRI to aid in diagnosing atypical Meniere disease and distinguishing it from other disease processes, such as migraine equivalent vertigo. The integration of historical temporal bone studies with modern MRI techniques offers valuable insights into the pathophysiology of otologic diseases. In addition, it emphasizes the importance of preserving and curating historical temporal bone collections for continued research and medical education purposes. Previous studies of delayed MRIs did not use Meniere disease temporal bone histopathology images.
PubMed: 38872311
DOI: 10.1177/01455613241261461 -
Journal of Ayurveda and Integrative... Jun 2024A 58-year-old non-diabetic, non-hypertensive, non-dyslipidemic, euthyroid lady with a known case of migraine for last 10 years approached our hospital complaining of a...
A 58-year-old non-diabetic, non-hypertensive, non-dyslipidemic, euthyroid lady with a known case of migraine for last 10 years approached our hospital complaining of a severe right-sided throbbing headache in the temple area and behind the right ear for three days. She approached our hospital as she did not get any relief from painkillers. An intensity of 10 was recorded on Visual Analogue Scale (VAS) and 8 on the Global Assessment of Migraine Severity (GAMS) Scale. The case was diagnosed to be vatika shirashula on ardhavabhedaka, with no pitta-rakta association. She was posted for Agnikarma therapy [AGT]. Immediately, within 2 min of application of AGT on her right temple, her intense pain reduced, and within 5 min she had no pain [zero on VAS scale and one on GAMS scale]. Samyak mamsa dagdha lakshana was achieved. AGT was tolerable and did not produce any major discomforts. No adverse effects were reported. Patient experienced a mild burning sensation over the AGT, and the blackish discoloration due to AGT faded off within 41 days. AGT could be used as a potent, cheap, fast-acting, adverse effect free emergency treatment for acute attacks of migraine headache.
PubMed: 38871596
DOI: 10.1016/j.jaim.2024.100953 -
Cureus May 2024The article aims to explore the challenges involved in diagnosing and managing Alice in Wonderland Syndrome (AIWS) in pediatric cases, focusing on an eight-year-old...
The article aims to explore the challenges involved in diagnosing and managing Alice in Wonderland Syndrome (AIWS) in pediatric cases, focusing on an eight-year-old female with perceptual distortions affecting vision, hearing, and time perception. AIWS, a rare neurological phenomenon, manifests as distortions in the perception of the body and external stimuli. The lack of established diagnostic criteria, particularly in the pediatric population, complicates accurate identification. The presented case illustrates visual anomalies, auditory abnormalities, and tachysensia, emphasizing the multisensory nature of AIWS. The temporal association with underlying causes, such as migraines and viral infections, highlights the need for a comprehensive evaluation. The Acharya Vinoba Bhave Rural Hospital management approach involves a systematic assessment, identification of underlying chronic conditions, and targeted treatment. Migraine prophylaxis, utilizing prescription drugs and a low-tyramine diet, plays a central role. The limited use of antipsychotics underscores the neurological origin of AIWS. The article contributes valuable insights into pediatric AIWS, advocating for further research and awareness. The article also aims to highlight the lack of established diagnostic criteria for AIWS, particularly in the pediatric population, and to present a systematic management approach based on a specific case study. The multidisciplinary collaboration, regular follow-ups, and patient education constitute a comprehensive approach to enhance understanding and alleviate symptoms in AIWS cases.
PubMed: 38868275
DOI: 10.7759/cureus.60182 -
Cureus May 2024Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an uncommon genetic disorder that affects small blood vessels in...
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an uncommon genetic disorder that affects small blood vessels in the brain. It leads to neurological symptoms, disability-adjusted life years, and difficult emotional and physical situations for patients and their families. As unusual brain symptoms appear, it becomes important to understand the different clinical manifestations of CADASIL. Our case report and review examine several cases to demonstrate different presentations and management strategies of CADASIL. A 52-year-old male with a family history of strokes at a young age from his father and paternal grandfather presented to a neurology clinic for left facial droop and drooling. Brain magnetic resonance imaging showed extensive periventricular and subcortical white matter disease, including the external capsule and subcortical white matter of the temporal lobe. Findings were suggestive of small vessel vasculopathy. A cerebral angiogram showed that all large extra- and intracranial vessels were patent without evidence of aneurysm formation. There was no obvious evidence of beading of the distal intracranial vessels. Cerebrospinal fluid studies were normal. The NOTCH3 mutation was sent to test for CADASIL, which came back positive. The patient was started on aspirin (81 mg) and atorvastatin (20 mg) daily. The patient was counseled on the possibility of having an ischemic or hemorrhagic stroke. Aspirin and atorvastatin were continued, a neuropsychological evaluation was ordered, and CADASIL genetic counseling and testing were offered to him and his children. Over several years, patients developed several strokes and seizures due to infarcts. He also developed intraparenchymal hemorrhage complicated by dysphagia, requiring a feeding tube. Due to his severe physical debility, he was discharged to a nursing home for rehabilitation, where he did not improve with therapy and remained bedbound. He was discharged and sent home with his family. CADASIL can present as a diagnostic challenge due to its common presentation with migraines, transient ischemic attacks, and strokes, with or without risk factors. This unique presentation of CADASIL with facial palsy highlights the importance of emerging atypical presentations and the need for a detailed history of neuroimaging, family history, and personal history of neurovascular events. By accurately diagnosing the condition, patients and families can be counseled on the disease course and genetics. Management requires a multidisciplinary approach with neurology, genetic counseling, physical therapy, psychology, and psychiatry if depression or anxiety is present, with the aim of improving the patient's quality of life.
PubMed: 38868233
DOI: 10.7759/cureus.60165 -
The Journal of Headache and Pain Jun 2024Currently, the treatment and prevention of migraine remain highly challenging. Mendelian randomization (MR) has been widely used to explore novel therapeutic targets....
BACKGROUND
Currently, the treatment and prevention of migraine remain highly challenging. Mendelian randomization (MR) has been widely used to explore novel therapeutic targets. Therefore, we performed a systematic druggable genome-wide MR to explore the potential therapeutic targets for migraine.
METHODS
We obtained data on druggable genes and screened for genes within brain expression quantitative trait locis (eQTLs) and blood eQTLs, which were then subjected to two-sample MR analysis and colocalization analysis with migraine genome-wide association studies data to identify genes highly associated with migraine. In addition, phenome-wide research, enrichment analysis, protein network construction, drug prediction, and molecular docking were performed to provide valuable guidance for the development of more effective and targeted therapeutic drugs.
RESULTS
We identified 21 druggable genes significantly associated with migraine (BRPF3, CBFB, CDK4, CHD4, DDIT4, EP300, EPHA5, FGFRL1, FXN, HMGCR, HVCN1, KCNK5, MRGPRE, NLGN2, NR1D1, PLXNB1, TGFB1, TGFB3, THRA, TLN1 and TP53), two of which were significant in both blood and brain (HMGCR and TGFB3). The results of phenome-wide research showed that HMGCR was highly correlated with low-density lipoprotein, and TGFB3 was primarily associated with insulin-like growth factor 1 levels.
CONCLUSIONS
This study utilized MR and colocalization analysis to identify 21 potential drug targets for migraine, two of which were significant in both blood and brain. These findings provide promising leads for more effective migraine treatments, potentially reducing drug development costs.
Topics: Humans; Migraine Disorders; Mendelian Randomization Analysis; Genome-Wide Association Study; Quantitative Trait Loci; Genetic Predisposition to Disease; Brain
PubMed: 38867170
DOI: 10.1186/s10194-024-01805-3 -
Clinical Ophthalmology (Auckland, N.Z.) 2024To assess ocular pain in patients undergoing multiple intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) who have previous factors that may...
PURPOSE
To assess ocular pain in patients undergoing multiple intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) who have previous factors that may influence pain sensitivity.
METHODOLOGY
This is a prospective, observational, case series study involving patients who underwent multiple (≥3) pro re nata intravitreal injections of ranibizumab or aflibercept to treat any cause of chorioretinal vascular disease. Ocular pain was assessed by the numerical analog scale during intravitreal injection. For this study, the main variable was ocular pain and the secondary variables included age, sex, previous history of glaucoma, primary retinal vascular disease, severe dry eye history, trigeminal pain, scleral buckle surgery, collagen diseases, fibromyalgia, severe migraine history, pars plana vitrectomy, scleral thickness measurements, and type of anti-VEGF.
RESULTS
In a total of 894 patients, 948 eyes (4822 intravitreal injections), 793 patients (88.6%) had ocular pain sensitivity between no pain to mild pain, 80 patients (8.9%) had moderate ocular pain, 15 patients (1.6%) had severe ocular pain, and 6 patients (0.7%) had extremely severe ocular pain. Patients with severe dry eye (p = 0.01) and previous history of scleral buckle surgery (p = 0.01) showed a significant correlation with ocular pain during intravitreal injection. Pars plana scleral thickness (>550 um) and diabetic neuropathy were associated with ocular pain but did not meet the criteria for statistical significance (p = 0.09 and p = 0.06, respectively).
CONCLUSION
Dry eye and prior scleral buckle surgery may contribute to pain associated with intravitreal injection. These issues should be taken into consideration in patients undergoing multiple intravitreal injections.
PubMed: 38863678
DOI: 10.2147/OPTH.S463016