RESUMO
Patients with visual snow syndrome suffer from a continuous pan-field visual disturbance, additional visual symptoms, tinnitus, and non-perceptional symptoms. The pathophysiology of visual symptoms might involve dysfunctional visual cortex. So far, the extra-visual system has not been investigated. We aimed at identifying structural and functional correlates for visual and non-visual symptoms in visual snow syndrome. Patients were compared to age- and sex-matched controls using 18F-2-fluoro-2-deoxy-d-glucose PET (n = 20 per group) and voxel-based morphometry (n = 17 per group). Guided by the PET results, region of interest analysis was done in voxel-based morphometry to identify structural-functional correspondence. Grey matter volume was assessed globally. Patients had corresponding hypermetabolism and cortical volume increase in the extrastriate visual cortex at the junction of the right lingual and fusiform gyrus. There was hypometabolism in the right superior temporal gyrus and the left inferior parietal lobule. Patients had grey matter volume increases in the temporal and limbic lobes and decrease in the superior temporal gyrus. The corresponding structural and functional alterations emphasize the relevance of the visual association cortex for visual snow syndrome. The broad structural and functional footprint, however, confirms the clinical impression that the disorder extends beyond the visual system.
Assuntos
Encéfalo/fisiopatologia , Transtornos da Visão/fisiopatologia , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Neuroimagem/métodos , Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Síndrome , Transtornos da Visão/diagnóstico por imagem , Transtornos da Visão/patologia , Adulto JovemRESUMO
PURPOSE: While previous studies have estimated health state utilities associated with migraine severity and frequency, migraine treatments vary in other ways that may have an impact on patients' quality of life, preference, and utility. The purpose of this study was to estimate utilities associated with migraine treatment attributes including route of administration and treatment-related adverse events (AEs). METHODS: In time trade-off interviews, migraine patients and general population participants in the UK valued health state vignettes drafted based on literature, medication labels, and clinician interviews. All respondents valued migraine health states varying in route of administration. Each participant also valued eight health states (randomly selected from a total of 15) that added the description of an AE to a migraine health state. RESULTS: A total of 400 participants completed interviews (200 general population [49.0% female; mean age = 43.6 years]; 200 migraine patients [74.5% female; mean age = 45.8 years]). In the general population sample, mean utilities of health states without aura were 0.79 with daily oral medication, 0.78 with one injection per month, and 0.72 with 31-39 injections once every 3 months. The greatest disutilities (i.e., decreases in utility) were for AEs associated with oral medications (e.g., - 0.060 [fatigue] and - 0.098 [brain fog]). Differences among health states followed the same pattern in the patient sample as in the general population sample. CONCLUSIONS: Utilities estimated from the general population sample may be used to represent route of administration and AEs in cost-utility models. Results from the patient sample indicate that these treatment characteristics have an impact on patient preference.
Assuntos
Transtornos de Enxaqueca/prevenção & controle , Preferência do Paciente/psicologia , Qualidade de Vida/psicologia , Adulto , Feminino , Humanos , Masculino , Transtornos de Enxaqueca/terapia , Projetos PilotoRESUMO
SEE DREIER DOI 101093/AWW112 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: For many decades a breakdown of the blood-brain barrier has been postulated to occur in migraine. Hypothetically this would facilitate access of medications, such as dihydroergotamine or triptans, to the brain despite physical properties otherwise restricting their entry. We studied the permeability of the blood-brain barrier in six migraineurs and six control subjects at rest and during acute glyceryl trinitrate-induced migraine attacks using positron emission tomography with the novel radioligand (11)C-dihydroergotamine, which is chemically identical to pharmacologically active dihydroergotamine. The influx rate constant Ki, average dynamic image and time activity curve were assessed using arterial blood sampling and served as measures for receptor binding and thus blood-brain barrier penetration. At rest, there was binding of (11)C-dihydroergotamine in the choroid plexus, pituitary gland, and venous sinuses as expected from the pharmacology of dihydroergotamine. However, there was no binding to the brain parenchyma, including the hippocampus, the area with the highest density of the highest-affinity dihydroergotamine receptors, and the raphe nuclei, a postulated brainstem site of action during migraine, suggesting that dihydroergotamine is not able to cross the blood-brain barrier. This binding pattern was identical in migraineurs during glyceryl trinitrate-induced migraine attacks as well as in matched control subjects. We conclude that (11)C-dihydroergotamine is unable to cross the blood-brain barrier interictally or ictally demonstrating that the blood-brain barrier remains tight for dihydroergotamine during acute glyceryl trinitrate-induced migraine attacks.
Assuntos
Barreira Hematoencefálica , Di-Hidroergotamina/metabolismo , Transtornos de Enxaqueca , Nitroglicerina/farmacologia , Tomografia por Emissão de Pósitrons/métodos , Vasoconstritores/metabolismo , Vasodilatadores/farmacologia , Adulto , Barreira Hematoencefálica/diagnóstico por imagem , Barreira Hematoencefálica/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/diagnóstico por imagem , Transtornos de Enxaqueca/metabolismoRESUMO
This review aims to understand the prevalence of premonitory symptoms in migraine, postulate their mechanisms, and compare these with functional imaging studies. A thorough literature review was conducted using PubMed for prevalence studies of premonitory symptoms in migraine and functional imaging studies in the premonitory phase. The majority of studies have been retrospective reporting a prevalence of 7-88% for premonitory symptoms in migraine. Only one study has investigated premonitory symptoms prospectively and used preselected patients with recognized premonitory symptoms. The majority of patients were able to predict correctly the onset of migraine headache. Only one functional imaging study has been conducted in the premonitory phase that showed activation of posterolateral hypothalamus, midbrain tegmental area and substantia nigra, periaqueductal gray, dorsal pons, and various cortical areas including occipital, temporal, and prefrontal cortex. Subgroup analysis of patients with photophobia more than without photophobia in the premonitory phase showed activation of the occipital cortex. Comparison of patients with nausea more than without nausea in the premonitory phase showed activation in upper dorsal medulla and periaqueductal gray. Premonitory symptoms are common in migraine, although the true prevalence cannot be stated with certainty in the absence of prospective studies in unselected patients. Hypothalamic involvement can explain many of the premonitory symptoms. Activation of the the brainstem structures and hypothalamus before pain suggests a pivotal role of these structures in the pathogenesis of migraine. Hypersensitivity to light and occurrence of nausea in migraine is associated with activation of central brain structures involved in these pathways, and this can occur in the absence of pain.
Assuntos
Aprendizagem , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/etiologia , Humanos , Transtornos de Enxaqueca/epidemiologia , Náusea/complicações , Náusea/diagnóstico , Náusea/epidemiologia , Fotofobia/complicações , Fotofobia/diagnóstico , Fotofobia/epidemiologia , Estudos Prospectivos , Estudos RetrospectivosRESUMO
Our aim was identify brain areas involved in the premonitory phase of migraine using functional neuroimaging. To this end, we performed positron emission tomography scans with H2(15)O to measure cerebral blood flow as a marker of neuronal activity. We conducted positron emission tomography scans at baseline, in the premonitory phase without pain and during migraine headache in eight patients. We used glyceryl trinitrate (nitroglycerin) to trigger premonitory symptoms and migraine headache in patients with episodic migraine without aura who habitually experienced premonitory symptoms during spontaneous attacks. The main outcome was comparing the first premonitory scans in all patients to baseline scans in all patients. We found activations in the posterolateral hypothalamus, midbrain tegmental area, periaqueductal grey, dorsal pons and various cortical areas including occipital, temporal and prefrontal cortex. Brain activations, in particular of the hypothalamus, seen in the premonitory phase of glyceryl trinitrate-triggered migraine attacks can explain many of the premonitory symptoms and may provide some insight into why migraine is commonly activated by a change in homeostasis.
Assuntos
Encéfalo/diagnóstico por imagem , Enxaqueca sem Aura/induzido quimicamente , Enxaqueca sem Aura/diagnóstico por imagem , Nitroglicerina , Vasodilatadores , Adulto , Circulação Cerebrovascular/fisiologia , Interpretação Estatística de Dados , Progressão da Doença , Feminino , Humanos , Hipotálamo/patologia , Processamento de Imagem Assistida por Computador , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Substância Cinzenta Periaquedutal/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
Patients with 'visual snow' report continuous tiny dots in the entire visual field similar to the noise of an analogue television. As they frequently have migraine as a comorbidity with ophthalmological, neurological and radiological studies being normal, they are offered various diagnoses, including persistent migraine aura, post-hallucinogen flashback, or psychogenic disorder. Our aim was to study patients with 'visual snow' to characterize the phenotype. A three-step approach was followed: (i) a chart review of patients referred to us identified 22 patients with 'visual snow'. Fifteen had additional visual symptoms, and 20 patients had comorbid migraine, five with aura; (ii) to identify systematically additional visual symptoms, an internet survey (n = 275) of self-assessed 'visual snow' subjects done by Eye On Vision Foundation was analysed. In two random samples from 235 complete data sets, the same eight additional visual symptoms were present in >33% of patients: palinopsia (trailing and afterimages), entoptic phenomena (floaters, blue field entoptic phenomenon, spontaneous photopsia, self-light of the eye), photophobia, and nyctalopia (impaired night vision); and (iii) a prospective semi-structured telephone interview in a further 142 patients identified 78 (41 female) with confirmed 'visual snow' and normal ophthalmological exams. Of these, 72 had at least three of the additional visual symptoms from step (ii). One-quarter of patients had 'visual snow' as long as they could remember, whereas for the others the mean age of onset was 21 ± 9 years. Thirty-two patients had constant visual symptoms, whereas the remainder experienced either progressive or stepwise worsening. Headache was the most frequent symptom associated with the beginning or a worsening of the visual disturbance (36%), whereas migraine aura (seven patients) and consumption of illicit drugs (five, no hallucinogens) were rare. Migraine (59%), migraine with aura (27%), anxiety and depression were common comorbidities over time. Eight patients had first degree relatives with visual snow. Clinical investigations were not contributory. Only a few treatment trials have been successful in individual patients. Our data suggest that 'visual snow' is a unique visual disturbance clinically distinct from migraine aura that can be disabling for patients. Migraine is a common concomitant although standard migraine treatments are often unhelpful. 'Visual snow' should be considered a distinct disorder and systematic studies of its clinical features, biology and treatment responses need to be commenced to begin to understand what has been an almost completely ignored problem.
Assuntos
Enxaqueca com Aura/complicações , Transtornos da Percepção/etiologia , Campos Visuais/fisiologia , Adolescente , Adulto , Feminino , Humanos , Drogas Ilícitas , Masculino , Pessoa de Meia-Idade , Enxaqueca com Aura/epidemiologia , Transtornos da Percepção/diagnóstico , Transtornos da Percepção/epidemiologia , Estimulação Luminosa , Estudos Retrospectivos , Transtornos Relacionados ao Uso de Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adulto JovemRESUMO
Trigeminal autonomic cephalalgias (TAC) are rare. Cluster headaches comprise the majority, with short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) being the rarest and shortest in duration. The majority of SUNCT are primary with a few cases occurring secondary to posterior fossa or pituitary lesions. Although activities like exercise or blowing of the nose can trigger SUNCT, onset during orgasm has not been described. Short-lasting aura has been described in TACs including SUNCT, but persistence of focal symptoms and signs without an underlying structural lesion have not been described. Lastly, treatment of SUNCT is difficult, with lamotrigine being the most common effective reported. We report a case of episodic SUNCT with symptoms suggestive of brainstem stroke that completely resolved spontaneously for which no underlying structural cause was found. The onset of first attack occurred during orgasm, and the patient responded to a high dose of topiramate.
Assuntos
Frutose/análogos & derivados , Fármacos Neuroprotetores/uso terapêutico , Cefalalgias Autonômicas do Trigêmeo/tratamento farmacológico , Adulto , Feminino , Frutose/uso terapêutico , Cefaleia/complicações , Humanos , Topiramato , Cefalalgias Autonômicas do Trigêmeo/complicaçõesRESUMO
OBJECTIVE: To assess the relationship between the phenotype of the "visual snow" syndrome, comorbid migraine, and typical migraine aura on a clinical basis and using functional brain imaging. BACKGROUND: Patients with "visual snow" suffer from continuous TV-static-like tiny flickering dots in the entire visual field. Most patients describe a syndrome with additional visual symptoms of the following categories: palinopsia ("afterimages" and "trailing"), entopic phenomena arising from the optic apparatus itself (floaters, blue field entoptic phenomenon, photopsia, self-light of the eye), photophobia, nyctalopia (impaired night vision), as well as the non-visual symptom tinnitus. The high prevalence of migraine and typical migraine aura in this population has led to the assumption that "visual snow" is caused by persistent migraine aura. Due to the lack of objective measures, alternative diagnoses are malingering or a psychogenic disorder. METHODS: (1) The prevalence of additional visual symptoms, tinnitus, and comorbid migraine as well as typical migraine aura was assessed in a prospective semi-structured telephone interview of patients with "visual snow." Correlations were calculated using standard statistics with P < .05 being considered statistically significant. (2) Areas with increased brain metabolism in a group of "visual snow" patients in comparison to healthy controls were identified using [(18) F]-2-fluoro-2-deoxy-D-glucose positron emission tomography and statistical parametric mapping (SPM8 with whole brain analysis; statistical significance was defined by P < .001 uncorrected for multiple comparisons). RESULTS: (1) Of 120 patients with "visual snow," 70 patients also had migraine and 37 had typical migraine aura. Having comorbid migraine was associated with an increased likelihood of having palinopsia (odds ratio [OR] 2.8; P = .04 for "afterimages" and OR 2.6; P = .01 for "trailing"), spontaneous photopsia (OR 2.9; P = .004), photophobia (OR 3.2; P = .005), nyctalopia (OR 2.7; P = .01), and tinnitus (OR 2.9; P = .006). Typical migraine aura was associated with an increased likelihood of spontaneous photopsia (OR 2.4; P = .04). (2) After adjusting for typical migraine aura, comparison of 17 "visual snow" patients with 17 age and gender matched controls showed brain hypermetabolism in the right lingual gyrus (Montreal Neurological Institute coordinates 16-78-5; kE = 101; ZE = 3.41; P < .001) and the left cerebellar anterior lobe adjacent to the left lingual gyrus (Montreal Neurological Institute coordinates -12-62-9; kE = 152; ZE = 3.28; P = .001). CONCLUSIONS: -Comorbid migraine aggravates the clinical phenotype of the "visual snow" syndrome by worsening some of the additional visual symptoms and tinnitus. This might bias studies on "visual snow" by migraineurs offering study participation more likely than non-migraineurs due to a more severe clinical presentation. The independence of entoptic phenomena from comorbid migraine indicates "visual snow" is the main determinant. The hypermetabolic lingual gyrus confirms a brain dysfunction in patients with "visual snow." The metabolic pattern differs from interictal migraine with some similarities to migrainous photophobia. The findings support the view that "visual snow," migraine, and typical migraine aura are distinct syndromes with shared pathophysiological mechanisms that need to be addressed in order to develop rational treatment strategies for this disabling condition.
Assuntos
Transtornos de Enxaqueca/complicações , Enxaqueca com Aura/complicações , Transtornos da Visão/complicações , Transtornos da Visão/diagnóstico por imagem , Adulto , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Masculino , Transtornos de Enxaqueca/epidemiologia , Enxaqueca com Aura/epidemiologia , Tomografia por Emissão de Pósitrons , PrevalênciaRESUMO
BACKGROUND: Nausea is a common and disabling symptom of migraine. The origin of nausea is not well understood although functional connections between trigeminal neurons and the nucleus tractus solitarius may explain occurrence of nausea with pain. However, nausea occurs as a premonitory symptom in about a quarter of patients, suggesting that a primary brain alteration unrelated to the experience of pain may be the reason for nausea. METHODS: We performed positron emission tomography scans with H215O PET in premonitory phase of nitroglycerin-induced migraine and compared patients with and without nausea. RESULTS: The results showed activation in rostral dorsal medulla and periaqueductal grey (PAG) in the nausea group, which was absent in the no nausea group. The rostral dorsal medullary area included the nucleus tractus solitarius, dorsal motor nucleus of the vagus nerve and the nucleus ambiguus, all of which are thought to be involved in brain circuits mediating nausea. CONCLUSIONS: The results demonstrate that nausea can occur as a premonitory symptom in migraine, independent of pain and trigeminal activation. This is associated with activation of brain structures known to be involved in nausea. We conclude that nausea is a centrally driven symptom in migraine.
Assuntos
Encéfalo/diagnóstico por imagem , Transtornos de Enxaqueca/diagnóstico por imagem , Náusea/diagnóstico por imagem , Neurônios/diagnóstico por imagem , Adolescente , Adulto , Idoso , Mapeamento Encefálico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/complicações , Náusea/etiologia , Cintilografia , Adulto JovemRESUMO
Chronic migraine is a relatively common disorder in neurological terms that causes very significant disability at a high cost. The precise mechanisms behind the progression of episodic migraine to chronic migraine are not well understood. Functional neuro-imaging works on the basis that neuronal activations are associated with changes in regional cerebral blood flow, and it can help us answer some of these questions. In this review, we discuss important recent studies in chronic migraine or studies relating to increasing frequency of migraine attacks. The findings show that increasing frequency of migraine attacks is associated with changes in key brainstem areas, basal ganglia and various cortical areas involved in pain.
Assuntos
Tronco Encefálico/diagnóstico por imagem , Fluordesoxiglucose F18 , Imageamento por Ressonância Magnética/métodos , Transtornos de Enxaqueca/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Tronco Encefálico/fisiopatologia , Circulação Cerebrovascular , Doença Crônica , Progressão da Doença , Feminino , Humanos , Masculino , Transtornos de Enxaqueca/fisiopatologia , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Cluster headache (CH) is the most common of the trigeminal autonomic cephalalgias (TAC), presenting with excruciatingly severe, short-lasting, unilateral headache accompanied by cranial autonomic symptoms. Chronic CH occurs in 10-15% of patients. Deep brain stimulation in the posterior hypothalamic region (hDBS) is successful in treating about 60% of patients otherwise refractory to medical treatment. CASE: A 28-year-old man had hDBS for medically refractory left-sided chronic CH, with a resultant reduction in frequency and severity of his attacks. He developed recurrent paroxysms of sneezing soon after the stimulation was started that have reduced after increasing the pulse width from 60 to 90 µs. DISCUSSION: Stimulation of the brain in the region of the posterior hypothalamus could produce sneezing from activation of facial nerve parasympathetic or trigeminal afferent pathway activation through the trigeminohypothalamic tract, or through other central mechanisms. DBS in general offers the opportunity to illuminate our understanding of brain function and for CH offers particular opportunities to understand a devastating primary headache syndrome.
Assuntos
Cefaleia Histamínica/terapia , Estimulação Encefálica Profunda/efeitos adversos , Hipotálamo Posterior/fisiologia , Espirro/fisiologia , Adulto , Cefaleia Histamínica/diagnóstico , Humanos , MasculinoRESUMO
BACKGROUND: Migraine is a common neurological disease that disproportionately affects females and has a peak incidence during productive years, resulting in significant burden. OBJECTIVE: The aim of the study was to determine the cost effectiveness of erenumab for the preventive treatment of migraine. METHODS: A hybrid decision-tree plus Markov model was developed to evaluate the cost effectiveness of erenumab as a migraine treatment compared with best supportive care only for patients experiencing at least 4 monthly migraine days for whom at least two prior preventive treatments had failed. Clinical efficacy data were based on results from four randomized controlled trials of erenumab against placebo. The primary outcomes were costs, migraine days, and quality-adjusted life-years (QALYs). An incremental cost-effectiveness ratio (ICER) was estimated as the cost per QALY gained. The cost per migraine day avoided was also estimated, as were disaggregated direct and indirect costs. The analysis was conducted from Swedish societal and healthcare system perspectives based on total migraine, chronic migraine and episodic migraine populations, using a discount rate of 3% applied to both costs and health benefits and using year 2019 values. RESULTS: In the base-case deterministic analyses, erenumab treatment resulted in ICERs of Swedish krona (SEK) 34,696 (3310) and SEK301,565 (28,769) per QALY gained in the total migraine and episodic migraine populations, respectively. Erenumab was dominant in the chronic migraine population. In the total migraine population, the use of erenumab resulted in a net benefit to society of SEK81,739 (7773) per patient, assuming a willingness-to-pay threshold of SEK300,000 (28,528) per QALY. CONCLUSIONS: Our analysis suggests that erenumab is a cost-effective treatment for migraine with a willingness-to-pay threshold of SEK300,000 per QALY.
Assuntos
Transtornos de Enxaqueca , Anticorpos Monoclonais Humanizados , Análise Custo-Benefício , Feminino , Humanos , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/prevenção & controle , Suécia , Falha de TratamentoRESUMO
Background: For novel migraine therapies, economic evaluations will be required to understand the trade-offs between additional health benefit and additional cost. The purpose of this study was to conduct a systematic literature review (SLR) to identify previous economic evaluations in migraine from the United Kingdom or Irish perspective to critically appraise these evaluations and to propose, if necessary, a novel modelling approach that can be used for future economic evaluations of migraine therapies.Methods: An SLR was conducted to identify previous economic evaluations of preventive migraine treatments. Key opinion leaders were consulted to determine the criteria for a robust migraine economic evaluation. Economic evaluations identified in the SLR were appraised against these criteria, and a novel cost-effectiveness model structure was then proposed.Results: Eight records reporting on published economic evaluations were identified and critically appraised for general quality. Expert consultation provided 6 recommendations on the ideal model structure for migraine that is both clinically and economically meaningful. A decision-tree plus Markov structure was then developed as a cost-effectiveness model for migraine therapies where each health state is associated with a patient distribution across monthly migraine day (MMD) frequencies.Conclusions: Future migraine economic evaluations should allow for assessments across the full spectrum of migraine, a response-based stopping rule, and the estimation of benefits and resource costs based on MMD frequency. The approach proposed in this paper captures all of the desired elements for an economic evaluation of migraine therapy and is suitable to assess new migraine therapies.
Assuntos
Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/economia , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Recursos em Saúde/economia , Serviços de Saúde/economia , Nível de Saúde , Humanos , Irlanda , Cadeias de Markov , Modelos Econômicos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Anos de Vida Ajustados por Qualidade de Vida , Índice de Gravidade de Doença , Reino UnidoRESUMO
Anticonvulsant hypersensitivity syndrome (AHS) is a rare, potentially life-threatening drug reaction which usually occurs after exposure to aromatic antiepileptics. AHS secondary to non-aromatic antiepileptics is even more rare and there are only few case reports of AHS presenting as aseptic meningitis. We present the case of a 48-year-old patient who presented with meningism within 3 weeks of adding lamotrigine for control of her juvenile myoclonic epilepsy. When lamotrigine was restarted 2 weeks later she developed similar but more severe symptoms which resolved on stopping lamotrigine. Our patient was subsequently rendered seizure free on levetiracetam which has not so far been linked with this syndrome. It is important to be aware of this life-threatening complication associated with the use of antiepileptics.