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The Journal of Headache and Pain Jul 2023Migraine headache attacks and accompanying sensory augmentation can be induced by several agents including levcromakalim (LVC), that is also capable of provoking...
BACKGROUND
Migraine headache attacks and accompanying sensory augmentation can be induced by several agents including levcromakalim (LVC), that is also capable of provoking aura-like symptoms in migraineurs. We investigated whether single LVC injection causes acute migraine-like phenotype in rats and induces/modulates cortical spreading depolarization (CSD), a rodent model of migraine aura.
METHODS
Wistar rats were administered LVC (1 mg/kg, i.p.) and compared to control (CTRL, vehicle, i.p.) and nitroglycerin (NTG, 10 mg/kg, i.p.) groups. Von Frey filaments were used to examine the periorbital and hind paw mechanical allodynia. Dark-light box (DLB), elevated plus maze (EPM), and open field arena (OFA) were used to evaluate light sensitivity and anxiety-related behaviors. The effects of LVC on CSD parameters, somatosensory evoked potentials, and baseline dural EEG (electroencephalography) were investigated. Possible CSD-induced c-fos expression was studied with Western Blot. Blood-brain barrier integrity in cortex was examined with Evans blue assay.
RESULTS
LVC and NTG administration robustly reduced periorbital mechanical thresholds in rats and induced anxiety-like behaviors and photophobia within 30 and 120 min, respectively. LVC induced migraine-like phenotype recovered in 2 h while NTG group did not fully recover before 4 h. Both LVC and NTG did not provoke DC (direct current) shift, EEG alterations or cortical c-fos expression characteristic to CSD. LVC did not induce de novo CSD and affect KCl (potassium chloride)-induced CSD parameters except for an increase in propagation failure. However, NTG significantly increased both CSD susceptibility and propagation failure. Somatosensory evoked potential (SSEP) configurations were not altered in both LVC and NTG groups, but SSEP latencies were prolonged after CSD. Acute LVC or NTG injection did not increase cortical BBB permeability.
CONCLUSIONS
Single LVC administration induced the fastest manifestation and recovery of acute migraine-like phenotype which was not mediated by CSD waves in the cerebral cortex. We suppose LVC triggered rapid-onset migraine-like symptoms are probably related to functional alterations in the trigeminal nociceptive system and K channel opening properties of LVC. Understanding the neurobiological mechanisms of this nociceptive window, may provide a novel target in migraine treatment.
Topics: Animals; Rats; Rats, Wistar; Cromakalim; Migraine Disorders; Cerebral Cortex; Phenotype
PubMed: 37488480
DOI: 10.1186/s10194-023-01627-9 -
BMC Neurology Nov 2023There have been very few real-world studies reported in the literature solely focusing on fremanezumab in Asia. This study aimed to evaluate the efficacy and safety of... (Observational Study)
Observational Study
BACKGROUND
There have been very few real-world studies reported in the literature solely focusing on fremanezumab in Asia. This study aimed to evaluate the efficacy and safety of fremanezumab in a real-world setting in Japan.
METHOD
This single-centered, observational, retrospective study examined patients with migraines who received four doses of fremanezumab between December 2021 and August 2022 at Keio University Hospital. We assessed the changes in monthly migraine days, responder rates, and migraine-associated symptoms, as well as injection site reactions and adverse events.
RESULT
Twenty-nine patients were enrolled, wherein 79.3% were women. Compared with those at baseline, the monthly migraine days decreased by 5.9 days at 4 months. The 50% responder rate was 55.2% at 4 months. A total of 57.9%, 47.8%, and 65.0% of patients showed improvement in the severity of photophobia, phonophobia, and nausea/vomiting, respectively. Moreover, injection site reactions were the most common adverse events (55.2%).
CONCLUSION
Fremanezumab is effective and safe for migraine prevention in Japan. Fremanezumab also improved migraine-associated symptoms in half of the patients.
Topics: Humans; Female; Male; Retrospective Studies; Japan; Injection Site Reaction; Treatment Outcome; Double-Blind Method; Migraine Disorders
PubMed: 37964188
DOI: 10.1186/s12883-023-03449-3 -
The Journal of Headache and Pain Sep 2023Migraine, a complex brain disorder, is regarded as a possible clinical manifestation of brain energy dysfunction. The trigeminovascular system is considered the basis...
BACKGROUND
Migraine, a complex brain disorder, is regarded as a possible clinical manifestation of brain energy dysfunction. The trigeminovascular system is considered the basis for the pathogenesis of migraine, hence we depicted the proteomics profiling of key regions in this system, then focusing on protein alterations related to mitochondrial function. The aim of this study is to illustrate the role of mitochondria in migraine.
METHODS
A mouse model of chronic migraine (CM) was established by repeated nitroglycerin (NTG) stimulation and evaluated by von-Frey filaments, a hot plate and a light-dark box. Differentially expressed proteins (DEPs) in some subcortical brain regions of the trigeminovascular system were screened through liquid chromatography-tandem mass spectrometry (LC‒MS/MS) to analyse the specificity of key signaling pathways in different brain regions. And then mitochondrial function, structure and dynamics were determined by qPCR, ELISA, and transmission electron microscope (TEM). Finally, the effect of mitochondrial intervention-Urolithin A (UA) on CM was investigated.
RESULTS
Repeated NTG injection triggered photophobia, periorbital and hind paw allodynia in mice. The proteomics profiling of CM model showed that 529, 109, 163, 152 and 419 DEPs were identified in the thalamus, hypothalamus, periaqueductal grey (PAG), trigeminal ganglion (TG) and trigeminocervical complex (TCC), respectively. The most significant changes in the brain region-specific pathways pointed to thalamic mitochondrial impairment. NTG induced mitochondrial structural disruption, dysfunction and homeostatic dysregulation, which could be partially attenuated by UA intervention.
CONCLUSION
Our findings highlight the involvement of mitochondrial damage in the thalamus in central sensitization of CM, which provides evidence of possible metabolic mechanisms in migraine pathophysiology.
Topics: Animals; Mice; Chromatography, Liquid; Proteomics; Tandem Mass Spectrometry; Migraine Disorders; Thalamus; Disease Models, Animal; Nitroglycerin
PubMed: 37667199
DOI: 10.1186/s10194-023-01646-6 -
European Journal of Neurology Aug 2023Photophobia is a sensory disturbance provoked by light. Little is known about the association between photophobia and dementia with Lewy bodies (DLB). In this study, we...
BACKGROUND AND OBJECTIVES
Photophobia is a sensory disturbance provoked by light. Little is known about the association between photophobia and dementia with Lewy bodies (DLB). In this study, we aimed to identify the frequency and the neural basis of photophobia in prodromal and mild DLB.
METHODS
One hundred and thirteen DLB patients, 53 Alzheimer's disease (AD) patients, 20 AD and DLB patients, 31 patients with other neurocognitive diseases (including prodromal and mild demented patients), and 31 healthy elderly controls were included in this case-control study. Photophobia was systematically looked for and compared between groups. Among a selection of 77 DLB patients, we used voxel-based morphometry (VBM) to compare those with and those without photophobia (gray matter volume; SPM12, XjView, and Matlab R2021b software).
RESULTS
The frequency of photophobia was higher in the DLB group (47.3%) than in the other groups (p = 0.002). The photophobia questionnaire score was higher in the DLB group than in the AD group (p = 0.001). Comparison between DLB patients with and those without photophobia showed decreased gray matter in the photophobia subgroup, in the right precentral cortex, in the eyelid motor region of Penfield's homunculus (p = 0.007, family-wise error [FWE] corrected).
CONCLUSIONS
Photophobia is a quite frequent symptom of prodromal and mild DLB. The neural basis of photophobia in DLB involves the right precentral cortex, which could have a role in the decrease of cerebral excitability, but also the motricity of the eyelids.
Topics: Humans; Aged; Lewy Body Disease; Alzheimer Disease; Case-Control Studies; Photophobia; Gray Matter; Prodromal Symptoms
PubMed: 37154398
DOI: 10.1111/ene.15829 -
Neurologia 2023Photophobia is a symptom of abnormal light intolerance without pain sensation that requires an anamnesis and an examination to diagnose an underlying etiology. (Review)
Review
INTRODUCTION
Photophobia is a symptom of abnormal light intolerance without pain sensation that requires an anamnesis and an examination to diagnose an underlying etiology.
BASIC PROCEDURE
This article focuses on 30 clinical cases with isolated intense photophobia and on the review of the literature.
OBJECTIVE
The purpose of this article is to establish diagnostic criteria for photophobia.
RESULTS
The etiology of photophobia appears to be at the level of the intrinsically photosensitive retinal ganglion cells known as melanopsin cells and at a neurochemical level mediated by calcitonin-related peptide and the pituitary activating peptide cyclase.
CONCLUSION
The treatment of photophobia could consist of monoclonal antibodies against calcitonin-related peptide and/or pituitary activating peptide cyclase.
Topics: Humans; Photophobia; Calcitonin; Migraine Disorders; Rod Opsins; Retinal Ganglion Cells
PubMed: 35842130
DOI: 10.1016/j.nrleng.2020.12.004 -
Cells Jan 2024Inflammatory bowel diseases (IBD) are multifactorial chronic inflammatory disorders affecting the gastrointestinal tract. However, a broad spectrum of extraintestinal... (Review)
Review
BACKGROUND AND AIMS
Inflammatory bowel diseases (IBD) are multifactorial chronic inflammatory disorders affecting the gastrointestinal tract. However, a broad spectrum of extraintestinal manifestations (EIMs) is associated with IBD, affecting several organs and systems, such as the skin, musculoskeletal and hepatobiliary systems, and, not least, the eye. Approximately 10% of IBD patients can develop ocular EIMs (O-EIMs) with a higher prevalence in Crohn's disease (CD). Eye-redness, photophobia, pain, and blurred vision are the common symptoms, with a wide rate of severity and clinical impact on the quality of life. This narrative review aims to summarize the prevalence, pathogenesis, and current evidence-based management of O-EIMs, underlying the importance of a holistic approach and specialties collaboration for a prompt diagnosis and treatment.
METHODS
PubMed was searched up to December 2023 to identify relevant studies investigating the pathogenesis, epidemiology, and treatment of O-EIMs in IBD patients.
RESULTS
The mechanisms underlying O-EIMs are partially unknown, encompassing immune dysregulation, shared antigens between the eye and the gut, genetic predisposition, and systemic inflammation driven by high levels of interleukins and cytokines in IBD patients. The complexity of O-EIMs' pathogenesis reflects in the management of these conditions, varying from topical and systemic steroids to immunomodulatory molecules and biologic therapy, such as anti-tumor necrosis factor (TNF)-alpha. A multidisciplinary approach is the backbone of the management of O-EIMs.
Topics: Humans; Quality of Life; Eye; Face; Inflammatory Bowel Diseases; Crohn Disease
PubMed: 38247834
DOI: 10.3390/cells13020142 -
Ophthalmic Epidemiology Aug 2023To determine the prevalence of ophthalmological findings suggesting an ocular cause for headache or occult neurological disease, among children with headache.
PURPOSE
To determine the prevalence of ophthalmological findings suggesting an ocular cause for headache or occult neurological disease, among children with headache.
METHODS
Retrospective cross-sectional study on children with headache at a tertiary outpatient ophthalmology clinic. All children underwent sensorimotor, anterior segment, and dilated fundoscopic examinations, with or without cycloplegic refraction. Prevalence of one or more new findings of ocular or occult neurological cause of headache, including glaucoma, uveitis, optic nerve elevation, or possible asthenopia from strabismus or refractive issues. Headache characteristics and associated symptoms were evaluated as risk factors for ocular findings.
RESULTS
Among 1,878 children with headache (mean age 10 yrs, range 2-18), 492 (26.1%, 95% CI 24.3-28.2%) children had one or more new ocular findings that could cause headache or indicate intracranial disease: refractive issues (342, 18.2%), strabismus (83, 4.4%), optic nerve elevation (51, 2.7%; 26 with papilledema, 25 with pseudopapilledema), uveitis (6, 0.3%), and glaucoma (2, 0.1%). Shorter headache duration was associated with ocular findings (p = .047), but headache frequency, photophobia, nausea/vomiting, and visual changes were not. In univariable analysis, visual changes (p ≤ .001), nausea/vomiting (p ≤ .002), and morning headache (p = .02) were associated with optic nerve elevation.
CONCLUSION
An ophthalmologic examination including cycloplegic refraction is indicated in children with headache, as one-quarter have a treatable ocular condition, which may be related to the headache, or sign of intracranial pathology. While nausea, visual changes, or morning headache should raise concern, coincident visual, ocular, or systemic symptoms are not reliable predictors of discovering ocular pathology in a child with headache.
Topics: Child; Humans; Child, Preschool; Adolescent; Retrospective Studies; Cross-Sectional Studies; Mydriatics; Strabismus; Refraction, Ocular; Headache; Glaucoma
PubMed: 36125107
DOI: 10.1080/09286586.2022.2125019 -
Frontiers in Pharmacology 2023To comprehensively reassess the efficacy and safety of different concentrations of atropine for retarding myopia progression and seek the most appropriate therapeutic...
To comprehensively reassess the efficacy and safety of different concentrations of atropine for retarding myopia progression and seek the most appropriate therapeutic concentration for clinical practice. We searched PubMed, Cochrane Library, Embase, Chinese Science and Technology Periodicals (VIP) and China National Knowledege Infrastructure (CNKI) from their inception to 23 March 2023, to obtain eligible randomized controlled trials (RCTs) and cohort studies that had atropine in at least one treatment arm and placebo/no intervention in another arm. We evaluated the risk of bias of the RCTs according to the recommendations of the Cochrane Collaboration for RCTs and quality of cohort studies by the Newcastle‒Ottawa Scale. Weighted mean difference (WMD), 95% confidence interval were calculated for meta-analysis. All data analyses were performed using Review Manager 5.3, STATA 12.0 and SPSS 26.0 software. A total of 44 studies were included in the meta-analysis. Weighted mean difference (WMD) were 0.73 diopters (D), 0.65 D, 0.35 D per year in refraction progression ( = 14.63, = 86.3%; < 0.001) and -0.26 mm, -0.37 mm, -0.11 mm per year in axial length progression ( = 5.80, = 65.5%; = 0.06) for high (0.5%-1%), moderate (0.1%-0.25%), and low (0.005%-0.05%) dose atropine groups, respectively. Logarithmic dose‒response correlations were found between atropine and their effect on change of refraction, axial length, accommodation and photopic pupil diameter. Through these curves, we found that atropine with concentrations ≤0.05% atropine resulted in a residual value of accommodation of more than 5 D and an increase in pupil diameter no more than 3 mm. Higher doses of atropine resulted in a higher incidence of adverse effects, of which the incidence of photophobia was dose-dependent ( = 0.477, = 0.029). Both the efficacy and risk of adverse events for atropine treatment of myopia were mostly dose dependent. Comprehensively considered the myopia control effect and safety of each dose, 0.05% may be the best concentration of atropine to control myopia progression at present, at which myopia is better controlled and the side effects are tolerable. https://www.crd.york.ac.uk/PROSPERO/#recordDetails, CRD42022377705.
PubMed: 37767401
DOI: 10.3389/fphar.2023.1227787 -
Journal of Clinical Medicine May 2024Migraine is a prevalent episodic brain disorder known for recurrent attacks of unilateral headaches, accompanied by complaints of photophobia, phonophobia, nausea, and... (Review)
Review
Migraine is a prevalent episodic brain disorder known for recurrent attacks of unilateral headaches, accompanied by complaints of photophobia, phonophobia, nausea, and vomiting. Two main categories of migraine are migraine with aura (MA) and migraine without aura (MO). Early twin and population studies have shown a genetic basis for these disorders, and efforts have been invested since to discern the genes involved. Many techniques, including candidate-gene association studies, loci linkage studies, genome-wide association, and transcription studies, have been used for this goal. As a result, several genes were pinned with concurrent and conflicting data among studies. It is important to understand the evolution of techniques and their findings. This review provides a chronological understanding of the different techniques used from the dawn of migraine genetic investigations and the genes linked with the migraine subtypes.
PubMed: 38731230
DOI: 10.3390/jcm13092701