Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 46
Filtrar
1.
Psychophysiology ; 61(7): e14566, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38509450

RESUMO

The primary goal of this study was to develop a parametric model that relates variation in stimulation of the trigeminal nerve to properties of the blink response. We measured blink responses in 17 healthy, adult participants to air puffs directed at the lateral canthus of the eye at five different, log-spaced intensities (3.5-60 PSI). Lid position over time was decomposed into amplitude and velocity components. We found that blink amplitude was systematically related to log stimulus intensity, with the relationship well described by a sigmoidal function. The parameters of the model fit correspond to the slope of the function and the stimulus intensity required to produce half of a maximal blink response (the half-response threshold). There was a reliable increase in the half-response threshold for the contralateral as compared to the ipsilateral blink response. This increase was consistent across participants despite substantial individual differences in the half-response threshold and slope parameters of the overall sensitivity function, suggesting that the laterality effect arises in the neural circuit subsequent to individual differences in sensitivity. Overall, we find that graded mechanical stimulation of the somatosensory trigeminal afferents elicits a graded response that is well described by a simple parametric model. We discuss the application of parametric measurements of the blink response to the detection of group differences in trigeminal sensitivity.


Assuntos
Piscadela , Nervo Trigêmeo , Humanos , Piscadela/fisiologia , Nervo Trigêmeo/fisiologia , Masculino , Adulto , Feminino , Adulto Jovem , Estimulação Física , Eletromiografia
2.
Proc Natl Acad Sci U S A ; 117(29): 17320-17329, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32632006

RESUMO

Second only to headache, photophobia is the most debilitating symptom reported by people with migraine. While the melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) are thought to play a role, how cone and melanopsin signals are integrated in this pathway to produce visual discomfort is poorly understood. We studied 60 people: 20 without headache and 20 each with interictal photophobia from migraine with or without visual aura. Participants viewed pulses of spectral change that selectively targeted melanopsin, the cones, or both and rated the degree of visual discomfort produced by these stimuli while we recorded pupil responses. We examined the data within a model that describes how cone and melanopsin signals are weighted and combined at the level of the retina and how this combined signal is transformed into a rating of discomfort or pupil response. Our results indicate that people with migraine do not differ from headache-free controls in the manner in which melanopsin and cone signals are combined. Instead, people with migraine demonstrate an enhanced response to integrated ipRGC signals for discomfort. This effect of migraine is selective for ratings of visual discomfort, in that an enhancement of pupil responses was not seen in the migraine group, nor were group differences found in surveys of other behaviors putatively linked to ipRGC function (chronotype, seasonal sensitivity, presence of a photic sneeze reflex). By revealing a dissociation in the amplification of discomfort vs. pupil response, our findings suggest a postretinal alteration in processing of ipRGC signals for photophobia in migraine.


Assuntos
Transtornos de Enxaqueca/metabolismo , Fotofobia/metabolismo , Células Ganglionares da Retina/fisiologia , Adulto , Feminino , Humanos , Masculino , Estimulação Luminosa , Pupila/fisiologia , Células Fotorreceptoras Retinianas Cones/fisiologia , Opsinas de Bastonetes/fisiologia
3.
Headache ; 61(7): 1040-1050, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34363408

RESUMO

OBJECTIVE: To summarize the unique aspects of managing headache in gender minorities and current research in this area including the potential relationship between gender-affirming hormone therapy (GAHT) and headache. BACKGROUND: The study of headache in gender minorities is intrinsically important. Gender minorities are medically underserved, and their medical care to date has been limited by socioeconomic disadvantages including stigma and an unsupportive clinical environment. Despite the rising population of transgender and gender-diverse adults and youth, headache research has also been limited. Knowledge of hormonal effects on headache in cisgender patients raises the question of possible effects of GAHT on transgender patients. METHODS/RESULTS: The manuscript is a narrative review of current best practices in treating transgender patients, including the use of appropriate terminology and ways to create a supportive environment. It also contains current guidelines on GAHT and reviews drug-drug interactions and secondary headache related to hormone therapy. We also review transgender headache research and related research on hormonal effects on headache in cisgender individuals. CONCLUSION: Creating a supportive environment for transgender and gender-diverse patients and being knowledgeable about GAHT are key to providing quality headache care. This review identifies further research needs for this population including the epidemiology of headache disorders in sexual minorities and the potential effects of GAHT on headache disorders in transgender patients.


Assuntos
Interações Medicamentosas , Transtornos da Cefaleia Primários/terapia , Transtornos da Cefaleia Secundários/terapia , Terapia de Reposição Hormonal , Guias de Prática Clínica como Assunto , Procedimentos de Readequação Sexual , Minorias Sexuais e de Gênero , Transtornos da Cefaleia Primários/tratamento farmacológico , Transtornos da Cefaleia Secundários/tratamento farmacológico , Transtornos da Cefaleia Secundários/etiologia , Terapia de Reposição Hormonal/efeitos adversos , Humanos , Guias de Prática Clínica como Assunto/normas , Procedimentos de Readequação Sexual/efeitos adversos
4.
Curr Pain Headache Rep ; 25(12): 82, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34910265

RESUMO

PURPOSE OF REVIEW: This review aims to discuss the experience of migraine in transgender and gender-diverse individuals as it relates to other psychiatric comorbidities such as anxiety, depression, PTSD, and others. As this population faces stigma and discrimination, literature posits that gender minority stress can also contribute to the experience of pain in these individuals. RECENT FINDINGS: Though there is little explicit data on these topics, more recent studies have explored the concept of gender minority stress and how stigma and discrimination can affect health outcomes and overall perception of health. These findings, as well as data on psychiatric comorbidities in cisgender individuals with migraine, can be extrapolated to understand how gender minority individuals may experience migraine. Research has demonstrated that stigma and discrimination can affect health outcomes in the transgender and gender-diverse community. A recent study has shown that sexual minority stress associated with stigma, discrimination, and barriers to care can exacerbate migraine. It is known that psychiatric comorbidities such as anxiety, depression, and PTSD can affect migraine frequency and severity in cisgender individuals. Though there are no specific studies in the transgender and gender-diverse patient population, these highly prevalent mental health conditions could potentially contribute to their migraine experience. Hormones, as well, may affect mood in those on gender-affirming hormone therapy, with some studies exploring how this may have both a direct and indirect relationship with migraine. There are clear knowledge gaps that can be addressed by future research in these areas to better understand the migraine experience in transgender and gender-diverse individuals and improve overall care.


Assuntos
Transtornos Mentais , Transtornos de Enxaqueca , Minorias Sexuais e de Gênero , Pessoas Transgênero , Humanos , Transtornos de Enxaqueca/epidemiologia , Estigma Social
5.
Cephalalgia ; 39(10): 1257-1266, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31042063

RESUMO

OBJECTIVE: To identify migraineurs and headache-free individuals with an online questionnaire and automated analysis algorithm. METHODS: We created a branching-logic, web-based questionnaire - the Penn Online Evaluation of Migraine - to obtain standardized headache history from a previously studied cohort. Responses were analyzed with an automated algorithm to assign subjects to one of several categories based on ICHD-3 (beta) criteria. Following a pre-registered protocol, the primary outcome was sensitivity and specificity for assignment of headache-free, migraine without aura, and migraine with aura labels, as compared to a prior classification by neurologist interview. RESULTS: Of 118 subjects contacted, 90 (76%) completed the questionnaire; of these 31 were headache-free controls, 29 migraine without aura, and 30 migraine with aura. Mean age was 41 ± 6 years and 76% were female. There were no significant demographic differences between groups. The median time to complete the questionnaire was 2.5 minutes (IQR: 1.5-3.4 minutes). Sensitivity of the Penn Online Evaluation of Migraine tool was 42%, 59%, 70%, and 83%, and specificity was 100%, 84%, 93%, and 90% for headache-free controls, migraine without aura, migraine with aura, and migraine overall, respectively. CONCLUSIONS: The Penn Online Evaluation of Migraine web-based questionnaire, and associated analysis routine, identifies headache-free and migraine subjects with good specificity. It may be useful for classifying subjects for large-scale research studies. Research study pre-registration: https://osf.io/sq9ef The following research study is a not a clinical trial.


Assuntos
Algoritmos , Internet , Transtornos de Enxaqueca/classificação , Transtornos de Enxaqueca/diagnóstico , Inquéritos e Questionários , Adulto , Feminino , Humanos , Masculino , Sensibilidade e Especificidade
6.
J Stroke Cerebrovasc Dis ; 28(10): 104286, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31327684

RESUMO

Calcitonin gene-related peptide (CGRP) is involved in nociception and neurogenic inflammation in migraine, but also serves as a potent vasodilator acting on intracranial arteries. This latter effect raises concern about the possibility of drugs inhibiting CGRP precipitating cerebral ischemia. We describe a 41-year-old woman with migraine without aura who developed a right thalamic infarction following a first dose of erenumab, a CGRP-receptor blocker. Stroke onset occurred during a typical migraine. Imaging demonsrated right posterior cerebral artery near-occlusion initially with normalization of the vessel at follow-up imaging 2 months later, suggesting vasospasm as a possible mechanism. Extensive evaluation revealed no other specific cause of stroke or vascular risk factors aside from long-term use of oral contraceptive pills. CGRP inhibitors might be associated with ischemic stroke due to blockade of normal cerebral vasodilatory regulatory function.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/efeitos adversos , Infarto da Artéria Cerebral Posterior/induzido quimicamente , Enxaqueca sem Aura/tratamento farmacológico , Artéria Cerebral Posterior/efeitos dos fármacos , Vasoespasmo Intracraniano/induzido quimicamente , Adulto , Feminino , Humanos , Infarto da Artéria Cerebral Posterior/diagnóstico por imagem , Infarto da Artéria Cerebral Posterior/tratamento farmacológico , Infarto da Artéria Cerebral Posterior/fisiopatologia , Enxaqueca sem Aura/diagnóstico , Artéria Cerebral Posterior/diagnóstico por imagem , Artéria Cerebral Posterior/fisiopatologia , Terapia Trombolítica , Resultado do Tratamento , Grau de Desobstrução Vascular/efeitos dos fármacos , Vasoespasmo Intracraniano/diagnóstico por imagem , Vasoespasmo Intracraniano/tratamento farmacológico , Vasoespasmo Intracraniano/fisiopatologia
7.
J Neurosci ; 37(1): 204-216, 2017 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-28053042

RESUMO

The neuropeptide calcitonin gene-related peptide (CGRP) is a key player in migraine. Although migraine can be treated using CGRP antagonists that act peripherally, the relevant sites of CGRP action remain unknown. To address the role of CGRP both within and outside the CNS, we used CGRP-induced light-aversive behavior in mice as a measure of migraine-associated photophobia. Peripheral (intraperitoneal) injection of CGRP resulted in light-aversive behavior in wild-type CD1 mice similar to aversion seen previously after central (intracerebroventricular) injection. The phenotype was also observed in C57BL/6J mice, although to a lesser degree and with more variability. After intraperitoneal CGRP, motility was decreased in the dark only, similar to motility changes after intracerebroventricular CGRP. In addition, as with intracerebroventricular CGRP, there was no general increase in anxiety as measured in an open-field assay after intraperitoneal CGRP. Importantly, two clinically effective migraine drugs, the 5-HT1B/D agonist sumatriptan and a CGRP-blocking monoclonal antibody, attenuated the peripheral CGRP-induced light aversion and motility behaviors. To begin to address the mechanism of peripheral CGRP action, we used transgenic CGRP-sensitized mice that have elevated levels of the CGRP receptor hRAMP1 subunit in nervous tissue (nestin/hRAMP1). Surprisingly, sensitivity to low light was not seen after intraperitoneal CGRP injection, but was seen after intracerebroventricular CGRP injection. These results suggest that CGRP can act in both the periphery and the brain by distinct mechanisms and that CGRP actions may be transmitted to the CNS via indirect sensitization of peripheral nerves. SIGNIFICANCE STATEMENT: The neuropeptide calcitonin gene-related peptide (CGRP) is a central player in migraine pathogenesis, yet its site(s) of action remains unknown. Some preclinical studies have pointed to central sites in the brain and brainstem. However, a peripheral site of action is indicated by the ability of intravenous CGRP to trigger migraine in humans and the efficacy of CGRP receptor antagonists that evidently do no penetrate the CNS in effective amounts. Resolving this issue is particularly important given recent clinical trials showing that anti-CGRP monoclonal antibodies can reduce and even prevent migraine attacks. In this study, we report that CGRP can act in both the brain and the periphery of the mouse to cause migraine-like photophobia by apparently distinct mechanisms.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Transtornos de Enxaqueca/psicologia , Fotofobia/psicologia , Animais , Ansiedade/psicologia , Peptídeo Relacionado com Gene de Calcitonina/administração & dosagem , Peptídeo Relacionado com Gene de Calcitonina/antagonistas & inibidores , Escuridão , Feminino , Injeções Intraperitoneais , Luz , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Atividade Motora , Nestina/genética , Proteína 1 Modificadora da Atividade de Receptores/genética , Agonistas do Receptor de Serotonina/farmacologia , Sumatriptana/farmacologia
8.
Molecules ; 22(9)2017 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-28880225

RESUMO

This paper reports the synthesis and characterization of silver oxide films for use as bactericidal coatings. Synthesis parameters, dissolution/elution rate, and bactericidal efficacy are reported. Synthesis conditions were developed to create AgO, Ag2O, or mixtures of AgO and Ag2O on surfaces by reactive magnetron sputtering. The coatings demonstrate strong adhesion to many substrate materials and impede the growth of all bacterial strains tested. The coatings are effective in killing Escherichia coli and Staphylococcus aureus, demonstrating a clear zone-of-inhibition against bacteria growing on solid media and the ability to rapidly inhibit bacterial growth in planktonic culture. Additionally, the coatings exhibit very high elution of silver ions under conditions that mimic dynamic fluid flow ranging between 0.003 and 0.07 ppm/min depending on the media conditions. The elution of silver ions from the AgO/Ag2O surfaces was directly impacted by the complexity of the elution media, with a reduction in elution rate when examined in complex cell culture media. Both E. coli and S. aureus were shown to bind ~1 ppm Ag⁺/mL culture. The elution of Ag⁺ resulted in no increases in mammalian cell apoptosis after 24 h exposure compared to control, but apoptotic cells increased to ~35% by 48 and 72 h of exposure. Taken together, the AgO/Ag2O coatings described are effective in eliciting antibacterial activity and have potential for application on a wide variety of surfaces and devices.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Óxidos/química , Óxidos/farmacologia , Compostos de Prata/química , Compostos de Prata/farmacologia , Prata/química , Células 3T3 , Animais , Sobrevivência Celular , Escherichia coli/efeitos dos fármacos , Humanos , Íons/química , Camundongos , Testes de Sensibilidade Microbiana/métodos , Staphylococcus aureus/efeitos dos fármacos , Propriedades de Superfície
9.
J Intensive Care Med ; 29(6): 348-56, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-23855040

RESUMO

PURPOSE: Methods to optimize positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome (ARDS) remain controversial despite decades of research. The pressure-volume curve (PVC), a graphical ventilator relationship, has been proposed for prescription of PEEP in ARDS. Whether the use of PVC's improves survival remains unclear. METHODS: In this systematic review, we assessed randomized controlled trials (RCTs) comparing PVC-guided treatment with conventional PEEP management on survival in ARDS based on the search of the National Library of Medicine from January 1, 1960, to January 1, 2010, and the Cochrane Central Register of Controlled Trials. Three RCTs were identified with a total of 185 patients, 97 with PVC-guided treatment and 88 with conventional PEEP management. RESULTS: The PVC-guided PEEP was associated with an increased probability of 28-day or hospital survival (odds ratio [OR] 2.7, 95% confidence interval [CI] 1.5, 4.9) using a random-effects model without significant heterogeneity (I (2) test: P = .75). The PVC-guided ventilator support was associated with reduced cumulative risk of mortality (-0.24 (95% CI -0.38, -0.11). The PVC-managed patients received greater PEEP (standardized mean difference [SMD] 5.7 cm H2O, 95% CI 2.4, 9.0) and lower plateau pressures (SMD -1.2 cm H2O, 95% CI -2.2, -0.2), albeit with greater hypercapnia with increased arterial pCO2 (SMD 8 mm Hg, 95% CI 2, 14). Weight-adjusted tidal volumes were significantly lower in PVC-guided than conventional ventilator management (SMD 2.6 mL/kg, 95% CI -3.3, -2.0). CONCLUSION: This analysis supports an association that ventilator management guided by the PVC for PEEP management may augment survival in ARDS. Nonetheless, only 3 randomized trials have addressed the question, and the total number of patients remains low. Further outcomes studies appear required for the validation of this methodology.


Assuntos
Cuidados Críticos/métodos , Tempo de Internação/estatística & dados numéricos , Respiração com Pressão Positiva , Síndrome do Desconforto Respiratório/terapia , Lesão Pulmonar Induzida por Ventilação Mecânica/prevenção & controle , Humanos , Consumo de Oxigênio , Respiração com Pressão Positiva/instrumentação , Respiração com Pressão Positiva/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Síndrome do Desconforto Respiratório/mortalidade , Análise de Sobrevida , Volume de Ventilação Pulmonar , Resultado do Tratamento , Lesão Pulmonar Induzida por Ventilação Mecânica/mortalidade
10.
J Emerg Med ; 47(3): 306-12, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24950943

RESUMO

BACKGROUND: Management of critically ill patients in austere environments is a logistic challenge. Availability of oxygen cylinders for the mechanically ventilated patient may be difficult in such a context. A solution is to use a ventilator able to function with an oxygen concentrator. OBJECTIVES: We tested the SeQual Integra™ (SeQual, San Diego, CA) 10-OM oxygen concentrator paired with the Pulmonetic System(®) LTV 1000 ventilator (Pulmonetic Systems, Minneapolis, MN) and evaluated the delivered fraction of inspired oxygen (FiO2) across a range of minute volumes and combinations of ventilator settings. METHODS: Two LTV 1000 ventilators were tested. The ventilators were attached to a test lung and FiO2 was measured by a gas analyzer. Continuous-flow oxygen was generated by the OC from 0.5 L/min to 10 L/min and injected into the oxygen inlet port of the LTV 1000. Several combinations of ventilator settings were evaluated to determine the factors affecting the delivered FiO2. RESULTS: The LTV 1000 ventilator is a turbine ventilator that is able to deliver high FiO2 when functioning with an oxygen concentrator. However, modifications of the ventilator settings such as increase in minute ventilation affect delivered FiO2 even if oxygen flow is constant on the oxygen concentrator. CONCLUSIONS: The ability of an oxygen concentrator to deliver high FiO2 when used with a turbine ventilator makes this method of oxygen delivery a viable alternative to cylinders in austere environments when used with a turbine ventilator. However, FiO2 has to be monitored continuously because delivered FiO2 decreases when minute ventilation is increased.


Assuntos
Oxigenoterapia/instrumentação , Oxigênio/análise , Respiração Artificial/métodos , Insuficiência Respiratória/terapia , Ventiladores Mecânicos/normas , Estado Terminal/terapia , Humanos , Oxigênio/administração & dosagem , Insuficiência Respiratória/fisiopatologia , Taxa Respiratória/fisiologia , Volume de Ventilação Pulmonar/fisiologia
11.
Prehosp Disaster Med ; 29(2): 212-3, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24576694

RESUMO

The case of a patient with a zone II penetrating neck injury who was intubated successfully utilizing the gum elastic bougie (GEB) is reported. He presented at a forward operational base in Afghanistan with a shrapnel wound in his neck as well as a cough and hoarseness. There were two wounds on each side of his laryngeal cartilages. The patient's breathing rate gradually increased and labored inhalation developed while the aeromedical evacuation was delayed for tactical reasons. Subcutaneous emphysema and edema concealed the anatomical landmarks, making a cricothyrotomy unsafe, and no fiber optic devices were available on site. Intratracheal intubation was decided upon by the doctors involved. Because of the anticipated difficultly of intubation, the GEB was used from the outset. During direct laryngoscopy, edema, blood, and mucus concealed the anatomic reliefs of the larynx. The glottis was not visible. On the second attempt, "clicks" were clearly perceived and the tube was railroaded over the bougie. Finally, the patient was evacuated to an Afghan military hospital. In this report, the benefit-risk balance for the use of the GEB in penetrating neck trauma is discussed. Although the use of the GEB cannot be recommended in all cases of penetrating neck injury, it should be considered as an option. This technique is not without risk, but in very remote settings or hostile environments, especially when cricothyrotomy is not possible, it can be lifesaving.


Assuntos
Intubação Intratraqueal/instrumentação , Lesões do Pescoço/terapia , Ferimentos por Arma de Fogo/terapia , Campanha Afegã de 2001- , Humanos , Laringoscopia , Masculino
12.
Front Neurol ; 15: 1399792, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38746660

RESUMO

Introduction: Calcitonin gene-related peptide (CGRP) plays an important role in cerebral vasodilation, so here we aim to quantify the impact of CGRP monoclonal antibody (mAb) therapy on cerebral hemodynamics. Methods: In 23 patients with chronic and episodic migraine, cerebral hemodynamic monitoring was performed (1) prior to and (2) 3-months into CGRP-mAb therapy. Transcranial Doppler monitored cerebral blood flow velocity (CBFv) in the middle cerebral artery (MCA) and posterior cerebral artery (PCA), from which cerebrovascular reactivity (CVR) and cerebral autoregulation (CA; Mx-index) were calculated. Results: CA was similar off and on treatment, in the MCA (p = 0.42) and PCA (p = 0.72). CVR was also unaffected by treatment, in the MCA (p = 0.38) and PCA (p = 0.92). CBFv and blood pressure were also unaffected. The subgroup of clinical responders (>50% reduction in migraine frequency) exhibited a small reduction in MCA-CBFv (6.0 cm/s; IQR: 1.1-12.4; p = 0.007) and PCA-CBFv (8.9 cm/s; IQR: 6.9-10.3; p = 0.04). Discussion: Dynamic measures of cerebrovascular physiology were preserved after 3 months of CGRP-mAb therapy, but a small reduction in CBFv was observed in patients who responded to treatment. Subgroup findings should be interpreted cautiously, but further investigation may clarify if CBFv is dependent on the degree of CGRP inhibition or may serve as a biomarker of drug sensitivity.

13.
J Neurosci ; 32(44): 15439-49, 2012 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-23115181

RESUMO

The neuropeptide calcitonin gene-related peptide (CGRP) plays a critical role in the pathophysiology of migraine. We have focused on the role of CGRP in photophobia, which is a common migraine symptom. We previously used an operant-based assay to show that CGRP-sensitized transgenic (nestin/hRAMP1), but not control, mice exhibited light aversion in response to an intracerebroventricular CGRP injection. A key question was whether the transgenic phenotype was due to overexpression of the CGRP receptor at endogenous or novel expression sites. We reasoned that if endogenous receptor sites were sufficient for light-aversive behavior, then wild-type mice should also show the phenotype when given a sufficiently strong stimulus. In this study, we report that mice with normal levels of endogenous CGRP receptors demonstrate light avoidance following CGRP administration. This phenotype required the combination of two factors: higher light intensity and habituation to the testing chamber. Control tests confirmed that light aversion was dependent on coincident exposure to CGRP and light and cannot be fully explained by increased anxiety. Furthermore, CGRP reduced locomotion only in the dark, not in the light. Coadministration of rizatriptan, a 5-HT(1B/D) agonist anti-migraine drug, attenuated the effects of exogenous CGRP on light aversion and motility. This suggests that triptans can act by mechanisms that are distinct from inhibition of CGRP release. Thus, we demonstrate that activation of endogenous CGRP receptors is sufficient to elicit light aversion in mice, which can be modulated by a drug commonly used to treat migraine.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina/antagonistas & inibidores , Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Fotofobia/induzido quimicamente , Receptor 5-HT1B de Serotonina/efeitos dos fármacos , Agonistas do Receptor de Serotonina/farmacologia , Animais , Ansiedade/psicologia , Comportamento Animal/efeitos dos fármacos , Feminino , Luz , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Estimulação Luminosa , Fotofobia/psicologia , Triazóis/farmacologia , Triptaminas/farmacologia
14.
Neurohospitalist ; 13(4): 415-418, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37701251

RESUMO

Background: Reversible cerebral vasoconstriction syndrome (RCVS) is a non-inflammatory vasculopathy. While most patients have good clinical outcomes, RCVS can be associated with severe brain injury from ischemic stroke, subarachnoid, and intracerebral hemorrhage. Purpose: A number of vasoactive medications have been implicated in RCVS, including triptans, amphetamines, antidepressants, and decongestants. Given the role of CGRP in modulating cerebral vasodilation, the possibility of CGRP inhibitors contributing to RCVS has been raised. Research Design: Case report at the University of Pennsylvania. Study Sample: Patient at the University of Pennsylvania. Results: We report a patient with RCVS in which severe exacerbation resulting in multifocal ischemic stroke occurred following administration of the calcitonin gene-related peptide (CGRP) inhibitor fremanezumab. Conclusions: It is unclear whether fremanezumab played a role in this patient's case, but CGRP-inhibitor use should be considered as a potential precipiating factor.

15.
Am J Emerg Med ; 30(6): 936-41, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21665418

RESUMO

OBJECTIVE: The aim of this study is to prospectively compare the accuracies of transcranial color-coded sonography (TCCS) and transcranial Doppler (TCD) in the diagnosis of elevated intracranial pressure. METHODS: A prospective, blinded, head-to-head comparison of TCD and TCCS methods using intracranial pressure (ICP) measured continuously via an intraparenchymal catheter as the reference standard in 2 groups of 20 neurocritical care patients each: high ICP (group 1) and normal ICP (group 2). Middle cerebral artery (MCA) pulsatility index (PI) recordings from all patients' sonographic reports were selected based on the highest left or right recorded MCA PI. Transcranial Doppler was performed using a dedicated TCD device, and TCCS was performed using a portable ultrasound system. RESULTS: The PI values obtained did not differ significantly between the 2 methods (group 1, P = .46; group 2, P = .11). Linear regression analysis identified a significant relationship between PI obtained with both methods (r = 0.897; P < .0001). The duration of PI measurement was statistically longer with TCCS than TCD (group 1, P < .01; group 2, P < .01). Diagnostic accuracies were good and similar for both methods (TCD area under curve, 0.901; TCCS area under curve 0.870; P = .69). CONCLUSIONS: This work is a pilot study comparing TCCS and TCD in the detection of elevated ICP. This study suggests that a bedside portable ultrasound system may be useful to determine MCA PI with accuracy similar to that of a dedicated TCD device.


Assuntos
Hipertensão Intracraniana/diagnóstico por imagem , Sistemas Automatizados de Assistência Junto ao Leito , Ultrassonografia Doppler Transcraniana/instrumentação , Feminino , Humanos , Pressão Intracraniana/fisiologia , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média/diagnóstico por imagem , Estudos Prospectivos , Método Simples-Cego , Ultrassonografia Doppler em Cores/instrumentação , Ultrassonografia Doppler em Cores/métodos
16.
Neurology ; 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36127137

RESUMO

Calcitonin gene-related peptide (CGRP) is involved in several of the pathophysiological processes underpinning migraine attacks. Therapies that target CGRP or its receptor have shown efficacy as preventive or acute treatments for migraine. Two small-molecule CGRP receptor antagonists (rimegepant and ubrogepant) are approved for the acute treatment of migraine, and four monoclonal antibodies (eptinezumab, erenumab, fremanezumab, and galcanezumab) are approved for migraine prevention; erenumab targets the canonical CGRP receptor, the others CGRP ligand. CGRP plays a role in gastrointestinal nociception, inflammation, gastric acid secretion, and motility. Nausea and vomiting are among the gastrointestinal symptoms associated with migraine, but individuals with migraine may also experience functional upper and lower gastrointestinal comorbidities, such as gastroesophageal reflux disease, gastroparesis, functional diarrhea or constipation, and irritable bowel syndrome. Although gastrointestinal symptoms in migraine can be treatment-related, they may also be attributable to increased CGRP. In this review, we summarize the epidemiological evidence for associations between migraine and gastrointestinal disorders, consider the possible physiological role of CGRP in these associations, and review the clinical occurrence of gastrointestinal events in patients with migraine receiving CGRP-based therapies and other migraine treatments. Because patients with migraine are at an increased risk of comorbid and treatment-related gastrointestinal effects, we also propose a patient-management strategy to mitigate these effects.

17.
Neurology ; 97(17): e1672-e1680, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34493620

RESUMO

BACKGROUND AND OBJECTIVES: To quantify interictal photophobia in migraine with and without aura using reflexive eye closure as an implicit measure of light sensitivity and to assess the contribution of melanopsin and cone signals to these responses. METHODS: Participants were screened to meet criteria for 1 of 3 groups: headache-free (HF) controls, migraine without aura (MO), and migraine with visual aura (MA). MO and MA participants were included if they endorsed ictal and interictal photophobia. Exclusion criteria included impaired vision, inability to collect usable pupillometry, and history of either head trauma or seizure. Participants viewed light pulses that selectively targeted melanopsin, the cones, or their combination during recording of orbicularis oculi EMG (OO-EMG) and blinking activity. RESULTS: We studied 20 participants in each group. MA and MO groups reported increased visual discomfort to light stimuli (discomfort rating, 400% contrast, MA: 4.84 [95% confidence interval 0.33, 9.35]; MO: 5.23 [0.96, 9.50]) as compared to HF controls (2.71 [0, 6.47]). Time course analysis of OO-EMG and blinking activity demonstrated that reflexive eye closure was tightly coupled to the light pulses. The MA group had greater OO-EMG and blinking activity in response to these stimuli (EMG activity, 400% contrast: 42.9%Δ [28.4, 57.4]; blink activity, 400% contrast: 11.2% [8.8, 13.6]) as compared to the MO (EMG activity, 400% contrast: 9.9%Δ [5.8, 14.0]; blink activity, 400% contrast: 4.7% [3.5, 5.9]) and HF control (EMG activity, 400% contrast: 13.2%Δ [7.1, 19.3]; blink activity, 400% contrast: 4.5% [3.1, 5.9]) groups. DISCUSSION: Our findings suggest that the intrinsically photosensitive retinal ganglion cells (ipRGCs), which integrate melanopsin and cone signals, provide the afferent input for light-induced reflexive eye closure in a photophobic state. Moreover, we find a dissociation between implicit and explicit measures of interictal photophobia depending on a history of visual aura in migraine. This implies distinct pathophysiology in forms of migraine, interacting with separate neural pathways by which the amplification of ipRGC signals elicits implicit and explicit signs of visual discomfort.


Assuntos
Piscadela/fisiologia , Transtornos de Enxaqueca/fisiopatologia , Fotofobia/fisiopatologia , Adulto , Eletromiografia , Feminino , Humanos , Masculino , Estimulação Luminosa , Reflexo Anormal/fisiologia , Células Fotorreceptoras Retinianas Cones/fisiologia , Células Ganglionares da Retina/fisiologia , Opsinas de Bastonetes/efeitos da radiação
19.
Mult Scler Relat Disord ; 29: 1-6, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30654245

RESUMO

The differential diagnosis for transverse myelitis is extensive, and the prognosis is highly variable depending on the etiology. We describe a rare case of a 56-year-old previously healthy male who presented with thoracic paresthesias and hyperesthesias involving the T6-11 dermatomes several weeks after a febrile illness. A thoracic MRI demonstrated a T7-10 transverse myelitis, and an exhaustive evaluation revealed neuroborreliosis. His symptoms improved significantly after an initial steroid course and 21 day course of ceftriaxone. We review neuroborreliosis and summarize the features of 23 previously reported cases of Lyme myelopathy. Although Lyme myelopathy is rare, including Lyme in the differential diagnosis of an acute transverse myelitis work up is important in endemic regions, as it is a potentially reversible disorder with a generally good prognosis when appropriately treated with antibiotics.


Assuntos
Neuroborreliose de Lyme/diagnóstico , Mielite Transversa/diagnóstico , Antibacterianos/farmacologia , Humanos , Neuroborreliose de Lyme/complicações , Neuroborreliose de Lyme/tratamento farmacológico , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mielite Transversa/tratamento farmacológico , Mielite Transversa/etiologia , Vértebras Torácicas
20.
Pediatr Neurol ; 91: 34-40, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30578049

RESUMO

BACKGROUND: Although migraine often starts in childhood or adolescence, hospital care for migraine in children is not well described. We examined patient and hospital characteristics associated with hospital care for migraine among children in the United States. METHODS: We queried the Kids' Inpatient Database (2003 to 2009) for hospitalizations of children aged 3-20. Sociodemographic and hospital characteristics were compared between hospitalizations for migraine and for other common medical conditions. Multivariate logistic regression models estimated the associations between patient, hospital, and socioeconomic characteristics and inpatient migraine care. RESULTS: We identified 11,696 pediatric migraine hospitalizations, the majority (68.7%) occurring at teaching hospitals, involving a female (68.8%) child, ages 13-20 (71%, mean age: 14.6 years). As compared to the overall inpatient sample, migraine hospitalizations were less likely to involve children who were Black (adjusted odds ratio [AOR] 0.54, 95% confidence interval [CI] 0.49 to 0.60), Hispanic (AOR = 0.58, 95% CI 0.50 to 0.68), or Asian (AOR = 0.42, 95% CI 0.32 to 0.55), and more likely to involve females (AOR = 1.49, 95% CI 1.40 to 1.59). Migraine inpatients were more likely to live in higher income postal ZIP code areas (versus lowest ZIP code income quartile: AOR = 1.32, 95% CI 1.18 to 1.48). The average length of stay for migraine was 2.54 (SEM 0.6) days. CONCLUSIONS: Children who are hospitalized for migraines have distinct sociodemographic characteristics and a short length of stay. Understanding the reasons for these variations will inform the design of interventions aimed at reducing the need for pediatric migraine hospitalization.


Assuntos
Hospitalização/estatística & dados numéricos , Transtornos de Enxaqueca/terapia , Adolescente , Adulto , Criança , Pré-Escolar , Etnicidade/estatística & dados numéricos , Feminino , Hospitais de Ensino/estatística & dados numéricos , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Transtornos de Enxaqueca/epidemiologia , Grupos Raciais/estatística & dados numéricos , Fatores Sexuais , Estados Unidos/epidemiologia , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA