RESUMO
In 1995, a committee of the International Headache Society developed and published the first edition of the Guidelines for Controlled Trials of Drugs in Cluster Headache. These have not been revised. With the emergence of new medications, neuromodulation devices and trial designs, an updated version of the International Headache Society Guidelines for Controlled Clinical Trials in Cluster Headache is warranted. Given the scarcity of evidence-based data for cluster headache therapies, the update is largely consensus-based, but takes into account lessons learned from recent trials and demands by patients. It is intended to apply to both drug and neuromodulation treatments, with specific proposals for the latter when needed. The primary objective is to propose a template for designing high quality, state-of-the-art, controlled clinical trials of acute and preventive treatments in episodic and chronic cluster headache. The recommendations should not be regarded as dogma and alternative solutions to particular methodological problems should be explored in the future and scientifically validated.
Assuntos
Cefaleia Histamínica , Humanos , Cefaleia Histamínica/tratamento farmacológico , Cefaleia/terapia , Ensaios Clínicos Controlados como AssuntoRESUMO
BACKGROUND: Contrary to pre-attack symptoms before an individual cluster headache attack, little is known about the pre-cluster symptoms before the onset of cluster bouts. We previously described pre-attack symptoms before cluster headache attacks. The aim of this study was to investigate characteristics of pre-cluster symptoms in patients with episodic cluster headache. METHODS: In this multicentre study, 184 patients with episodic cluster headache were recruited between October 2018 and December 2020. They were interviewed by investigators and completed a structured questionnaire. To investigate pre-cluster and pre-attack symptoms, we assessed 20 symptoms and signs using the questionnaire. RESULTS: The upcoming cluster bout was predictable in 35.3% (n = 65/184) of the patients. When present, pre-cluster symptoms occurred at a median duration of 7 days (interquartile range, 2.3-14 days) before the onset of the cluster bout. Patients with pre-cluster symptoms showed a higher proportion of women, prevalence of pre-attack symptoms and seasonal rhythmicity, frequency of cluster headache attacks per day, and total number of cluster bouts compared to patients without pre-cluster symptoms. In univariable and multivariable logistic regression analyses, female sex was associated with the predictability of pre-cluster symptoms (odds ratio = 2.297, p = 0.016). CONCLUSIONS: The upcoming cluster bout was predicted in approximately 35% of patients with episodic cluster headache, which may allow for an earlier preventive treatment and help understand the pathophysiology.
Assuntos
Cefaleia Histamínica , Cefaleia Histamínica/complicações , Cefaleia Histamínica/diagnóstico , Cefaleia Histamínica/epidemiologia , Estudos Transversais , Feminino , Humanos , Periodicidade , Prevalência , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To investigate the effect of chronic caffeine use and caffeine cessation on vasodilatory function in the posterior circulation in patients with migraine. BACKGROUND: Studies regarding cerebrovascular reactivity (CVR) using vasodilatory stimuli in patients with migraine have yielded conflicting results. We postulated that CVR may not be static, and caffeine might negatively affect vasodilatory function via its vasoconstrictive effect. METHODS: In this prospective longitudinal observation study, we recruited patients with episodic migraine who were 18-50 years of age and free of vascular risk factors at the Samsung Medical Center between August 2015 and March 2020. Patients were classified into caffeine users and non-users at baseline, and caffeine users were instructed to discontinue caffeine intake. We measured the mean breath-holding index (BHI) of bilateral posterior cerebral arteries (PCA) using transcranial Doppler in all the included patients at baseline and followed up after 3 months. We compared breath-holding indices cross-sectionally between caffeine users and non-users and analyzed BHI changes according to caffeine cessation. RESULTS: In total, 84 patients completed the study protocol. Cross-sectional analysis showed that the baseline BHI of PCA was lower in caffeine users (n = 56, 1.1 [interquartile range (IQR) 0.8-1.3]) than that in nonusers (n = 28, 1.3 [IQR 1.0-1.5], p = 0.030). In the longitudinal analysis, caffeine quitters showed a significant improvement in BHI in PCA (baseline 1.1 [IQR 0.8-1.2], follow-up 1.3 [IQR 1.0-1.4], p = 0.034), whereas continuous users and non-users did not. Multivariable analysis showed an independent effect of caffeine cessation on the changes in BHI of PCA (unstandardized ß = 0.27, 95% confidence interval 0.01-0.53, p = 0.044). CONCLUSION: In patients with migraine, caffeine use is associated with reduced CVR in the posterior circulation, and caffeine cessation might be beneficial in improving CVR.
Assuntos
Cafeína/efeitos adversos , Circulação Cerebrovascular/fisiologia , Transtornos de Enxaqueca/fisiopatologia , Vasodilatação/fisiologia , Adulto , Encéfalo/fisiopatologia , Suspensão da Respiração , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Masculino , Artéria Cerebral Média/fisiopatologia , Estudos Prospectivos , Ultrassonografia Doppler TranscranianaRESUMO
BACKGROUND: Previous studies have reported notable differences in demographic and clinical features of cluster headache between Western and Asian populations, including lower prevalence of the chronic type and in women. Recently, prodromal symptoms of migraine and pre-attack symptoms of cluster headache have drawn attention regarding their potential pathophysiological implications and pre-emptive treatment. However, pre-attack symptoms of cluster headache have not been studied in the Asian population. METHODS: A total of 136 patients with cluster headache (21 first-onset, 110 episodic, and five chronic cases) were recruited in this multi-center study between October 2018 and December 2019. We evaluated the characteristics of pre-attack symptoms in a current bout using a structured questionnaire. Univariable and multivariable logistic regression analyses were performed to evaluate the factors associated with presence of pre-attack symptoms. RESULTS: Pre-attack symptoms were reported in 71.3% of our patients with cluster headache. When present, pre-attack symptoms occurred at a median of 20 minutes (range 1-120) before the attack. The prevalence of local and painful, local and painless sensory, autonomic, and general symptoms was 58.8%, 14.7%, 11.0%, and 30.1%, respectively. Multivariable logistic regression analysis revealed that higher number of bouts was associated with higher prevalence of pre-attack symptoms (OR = 1.464, p = 0.044). CONCLUSIONS: Pre-attack symptoms were frequently observed in Korean patients with cluster headache, which was consistent with previous Western studies.
Assuntos
Cefaleia Histamínica , Cefaleia Histamínica/diagnóstico , Cefaleia Histamínica/epidemiologia , Humanos , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/epidemiologia , Prevalência , República da Coreia/epidemiologia , Inquéritos e QuestionáriosRESUMO
Background and Purpose- Reversible cerebral vasoconstriction syndrome (RCVS) has a unique temporal course of vasoconstriction. Blood-brain barrier (BBB) breakdown is part of the pathophysiology of RCVS, but its temporal course is unknown. We aimed to investigate the temporal profile of BBB breakdown and relevant clinical profiles in a large sample size. Methods- In this prospective observatory bicenter study, patients who underwent contrast-enhanced fluid-attenuated inversion recovery magnetic resonance imaging within 2 months from onset were included. The presence and extent of BBB breakdown were evaluated using contrast-enhanced fluid-attenuated inversion recovery magnetic resonance imaging. Contrast-enhanced fluid-attenuated inversion recovery magnetic resonance imaging data were analyzed using a semiautomated segmentation technique to quantitatively measure the area of Gadolinium leakage into cerebrospinal fluid space. The univariable and multivariable linear regressions were performed to investigate the independent effect of time from onset with adjustment for other covariates. Results- In the 186 patients with angiogram-proven RCVS included in this analysis, BBB breakdown was observed in 52.6%, 56.8%, 30.3%, 40.0%, and 23.8% in the first, second, third, fourth, and ≥fifth week after onset. The extent of BBB breakdown peaked at first and second week, whereas the peak of vasoconstriction was observed at the third week after onset. Multivariable analysis showed the second week from onset (ß, 3.35 [95% CI, 0.07-6.64]; P=0.046) and blood pressure surge (ß, 3.84 [95% CI, 1.75-5.92]; P<0.001) were independently associated with a greater extent of BBB breakdown. A synergistic effect of time from onset and blood pressure surge was found (P for interaction=0.006). Conclusions- Frequency and extent of BBB breakdown are more prominent during the early stage in patients with RCVS, with an earlier peak than that of vasoconstriction. The temporal course of BBB breakdown may provide a pathophysiologic background of the temporal course of neurological complications of RCVS.
Assuntos
Barreira Hematoencefálica/patologia , Transtornos Cerebrovasculares/patologia , Vasoconstrição/fisiologia , Vasoespasmo Intracraniano/patologia , Transtornos Cerebrovasculares/complicações , Feminino , Humanos , Angiografia por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Estudos Prospectivos , Vasoespasmo Intracraniano/diagnóstico , Vasoespasmo Intracraniano/etiologiaRESUMO
Dysregulated neural mechanisms in reward and somatosensory circuits result in an increased appetitive drive for and reduced inhibitory control of eating, which in turn causes obesity. Despite many studies investigating the brain mechanisms of obesity, the role of macroscale whole-brain functional connectivity remains poorly understood. Here, we identified a neuroimaging-based functional connectivity pattern associated with obesity phenotypes by using functional connectivity analysis combined with machine learning in a large-scale (n ~ 2,400) dataset spanning four independent cohorts. We found that brain regions containing the reward circuit positively associated with obesity phenotypes, while brain regions for sensory processing showed negative associations. Our study introduces a novel perspective for understanding how the whole-brain functional connectivity correlates with obesity phenotypes. Furthermore, we demonstrated the generalizability of our findings by correlating the functional connectivity pattern with obesity phenotypes in three independent datasets containing subjects of multiple ages and ethnicities. Our findings suggest that obesity phenotypes can be understood in terms of macroscale whole-brain functional connectivity and have important implications for the obesity neuroimaging community.
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Encéfalo/fisiopatologia , Conectoma , Rede Nervosa/fisiopatologia , Obesidade/fisiopatologia , Recompensa , Adulto , Idoso , Encéfalo/diagnóstico por imagem , Estudos de Coortes , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Obesidade/diagnóstico por imagem , Fenótipo , Adulto JovemRESUMO
OBJECTIVE: To investigate the temporal changes of circadian rhythmicity in relation to the disease course in patients with cluster headache. METHODS: In this multicenter study, patients with cluster headache were recruited between September 2016 and July 2018. We evaluated the patients for circadian rhythmicity and time of cluster headache attacks in the current bout and any experience of bout-to-bout change in circadian rhythmicity. We analyzed the patterns of circadian rhythmicity in relation to the disease progression (the number of total lifetime bouts, grouped into deciles). RESULTS: Of the 175 patients in their active, within-bout period, 86 (49.1%) had circadian rhythmicity in the current bout. The prevalence of circadian rhythmicity in the active period was overall similar regardless of disease progression. Sixty-three (46.3%) out of 136 patients with ≥2 bouts reported bout-to-bout changes in circadian rhythmicity. The most frequent time of cluster headache attacks was distributed evenly throughout the day earlier in the disease course and dichotomized into hypnic and midday as the number of lifetime bouts increased (p = 0.037 for the homogeneity of variance). When grouped into nighttime and daytime, nighttime attacks were predominant early in the disease course, while daytime attacks increased with disease progression (up to 7th deciles of total lifetime bouts, p = 0.001) and decreased in patients with the most advanced disease course (p = 0.013 for the non-linear association). CONCLUSIONS: Circadian rhythmicity is not a fixed factor, and changes according to the disease course. Our findings will be valuable in providing a new insight into the stability of functional involvement of the suprachiasmatic nucleus in the pathophysiology of cluster headache.
Assuntos
Ritmo Circadiano/fisiologia , Cefaleia Histamínica/diagnóstico , Cefaleia Histamínica/fisiopatologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: Our aim was to investigate the relationship between coexisting cluster headache (CH) and migraine with anxiety and depression during active cluster bouts, and how symptoms change during remission. METHODS: We analyzed data from 222 consecutive CH patients and 99 age- and sex-matched controls using a prospective multicenter registry. Anxiety or depression was evaluated using the Generalized Anxiety Disorder-7 (GAD-7) or Patient Health Questionnaire-9 (PHQ-9), respectively. Moderate-to-severe anxiety or depression was defined as a score of ≥10 at baseline (during a cluster bout). We assessed for changes in anxiety and depression during CH remission periods. RESULTS: Among the CH patients, the prevalence of moderate-to-severe anxiety and depression was seen in 38.2% and 34.6%, respectively. Compared with controls, CH patients were associated with moderate-to-severe anxiety and depression (multivariable-adjusted odds ratio [aOR] = 7.32, 95% confidence intervals [CI] = 3.35-15.99 and aOR = 4.95, 95% CI = 2.32-10.57, respectively). CH patients with migraine were significantly more likely to have moderate-to-severe anxiety and depression (aOR = 32.53, 95% CI = 6.63-159.64 and aOR = 16.88, 95% CI = 4.16-68.38, respectively), compared to controls without migraine. The GAD-7 and PHQ-9 scores were significantly reduced between cluster bout and remission periods (from 6.8 ± 5.6 to 1.6 ± 2.8; P < 0.001, and from 6.1 ± 5.0 to 1.8 ± 2.4; P < 0.001, respectively). CONCLUSIONS: Our results indicate that CH patients are at increased risk of anxiety and depression, especially in the presence of coexisting migraine. However, the anxiety and depression can improve during remission periods.
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Ansiedade/diagnóstico , Cefaleia Histamínica/diagnóstico , Depressão/diagnóstico , Transtornos de Enxaqueca/diagnóstico , Adolescente , Adulto , Ansiedade/epidemiologia , Ansiedade/psicologia , Cefaleia Histamínica/epidemiologia , Cefaleia Histamínica/psicologia , Comorbidade , Estudos Transversais , Depressão/epidemiologia , Depressão/psicologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/epidemiologia , Transtornos de Enxaqueca/psicologia , Prevalência , Estudos Prospectivos , Indução de Remissão , Adulto JovemRESUMO
BACKGROUND: Retinal migraine is an important differential diagnosis of recurrent transient monocular blindness accompanied by headache when other etiologies are excluded. Here, we report a case of orbital vasculitis which initially mimicked retinal migraine. CASE REPORT: A 47-year-old woman had recurrent episodes of fully reversible transient monocular blindness accompanied by ipsilateral headache for 15 months. The patient's neuroimaging and cardiac and ophthalmologic evaluations were normal. With a diagnosis of retinal migraine, her symptoms remitted in response to prophylactic treatment with topiramate and propranolol for 8 months. Three months after discontinuation of medications, transient monocular blindness recurred. High-resolution vessel wall magnetic resonance imaging revealed enhancement of the ipsilateral orbital vessels. Isolated orbital vasculitis was diagnosed. Complete remission of transient monocular blindness was achieved after steroid pulse therapy. DISCUSSION: Isolated orbital vasculitis should be considered in differential diagnosis of recurrent transient monocular blindness and ipsilateral headache. High-resolution vessel wall magnetic resonance imaging can be helpful for the diagnosis.
Assuntos
Amaurose Fugaz/etiologia , Vasculite/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Transtornos de Enxaqueca/diagnóstico , Órbita/patologia , Vasculite/complicaçõesRESUMO
BACKGROUND: *These authors are shared first authors. The recently published third edition of the International Classification of Headache Disorders (ICHD-3) revised the criteria for accompanying symptoms of cluster headache (CH) and the remission period of chronic cluster headache (CCH). This study aimed at testing the validity of the ICHD-3 criteria for CH by using data from the Korean Cluster Headache Registry. METHODS: Consecutive patients with CH and probable cluster headache (PCH) were prospectively recruited from 15 hospitals. We analysed the validity of the revised ICHD-3 criteria for CH against the beta version of the third edition of the ICHD (ICHD-3ß). RESULTS: In total, 193 patients were enrolled: 140 (72.5%), 5 (2.6%) and 22 (11.4%) had episodic cluster headache (ECH), CCH, and PCH, respectively. The remaining 26 (13.5%) had CH with undetermined remission periods. One patient with ECH and one with PCH had only forehead and facial flushing and were diagnosed with PCH and non-cluster headache, respectively, according to the ICHD-3. Four participants with ECH according to the ICHD-3ß had remission periods of > 1 month and between 1 and 3 months and were newly diagnosed with CCH according to the ICHD-3. CONCLUSION: The change from ICHD-3ß to ICHD-3 resulted in few differences in the diagnoses of CH and PCH.
Assuntos
Cefaleia Histamínica/diagnóstico , Classificação Internacional de Doenças , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de RegistrosRESUMO
OBJECTIVE: To investigate suicidality related to cluster headache and factors associated with increased suicidality in cluster headache patients. METHODS: In this multicenter study, 193 cluster headache patients were recruited between September 2016 and August 2018. Patients were asked about their suicidality during and between attacks, specifically about passive suicidal ideation, active suicidal ideation, suicide plan, and suicide attempt. Univariable and multivariable logistic regression analyses were performed to evaluate the factors associated with high ictal suicidality (sum of positive response ≥ 2). Patients were followed up when they were in the between-bouts period. RESULTS: A total of 175 cluster headache patients in the in-bout period were included in this study. Passive suicidal ideation, active suicidal ideation, suicidal planning, and suicidal attempt were reported by 111 (64.2%), 62 (35.8%), 10 (5.8%), and four (2.3%) patients during attacks; seven (4.0%), six (3.5%), five (2.9%) and two (1.2%) patients interictally; and none (0%), one (1.9%), one (1.9%), and none (0%) among patients in the between-bouts period. Factors associated with high ictal suicidality were longer disease duration, the Headache Impact Test score, and the Patient Health Question-9 score (multivariable OR = 1.90 per 10-year increase in disease duration, 95% CI = 1.18-3.05, p = 0.008; multivariable OR = 3.19 per 10-point increase in HIT-6, 95% CI = 1.73-5.87, p < 0.001; multivariable OR = 2.11 per 10-point increase in PHQ-9, 95% CI = 1.13-3.95, p = 0.020, respectively). CONCLUSIONS: Cluster headache attack carries a high suicidality compared to the interictal or between-bouts state. An intensive treatment to reduce cluster headache burden may be helpful to alleviate suicide risk in cluster headache patients.
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Cefaleia Histamínica/psicologia , Ideação Suicida , Suicídio Assistido , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Suicídio Assistido/psicologia , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: Most of the clinical characteristics of cluster headache (CH) have been established through the observation of men with CH. Epidemiological data of CH in women are scarce especially in the Asian population. Here, we sought to assess the prevalence and clinical characteristics of women with CH in comparison to men in a prospective CH registry. METHODS: Data used in this study were obtained from the Korean Cluster Headache Registry, a prospective, cross-sectional, multicenter headache registry that collected data from consecutive patients diagnosed with CH. Demographics and clinical characteristics were compared between the sexes. RESULTS: In total, 250 patients were enrolled in this study; 41 (16.4%) were women (male to female ratio 5.1:1). Mean age of onset did not differ between women and men (30.7 ± 15.5 vs 29.0 ± 11.1 years). The clinical features of CH in women and men were similar, with no differences in pain severity, duration, and attack frequency. Among autonomic features, facial and forehead sweating was significantly rare in women (4.9%) compared to men with CH (33.0%). Headache-related disability assessed by Headache Impact Test-6 did not differ between the sexes; however, depression scale assessed by Patients Health Questionnaire-9 (11.0 ± 8.5 vs 7.0 ± 5.8, P = .009) and stress (Perceived Stress Scale 4, 7.5 ± 3.4 vs 6.4 ± 3.0, P = .045) were significantly higher in women with CH. CONCLUSIONS: Although decreasing male preponderance was suggested in recent Western CH studies, CH in women is still far less prevalent than in men in the Korean population. Clinical and demographic characteristics were similar between the sexes. However, psychiatric comorbidities might be highly associated in women with CH.
Assuntos
Cefaleia Histamínica/diagnóstico , Cefaleia/diagnóstico , Adolescente , Adulto , Idade de Início , Idoso , Cefaleia Histamínica/epidemiologia , Estudos Transversais , Feminino , Cefaleia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Prevalência , Estudos Prospectivos , Sistema de Registros , República da Coreia/epidemiologia , Índice de Gravidade de Doença , Fatores Sexuais , Avaliação de Sintomas , Adulto JovemRESUMO
OBJECTIVE: To investigate the whole-brain resting-state functional connectivity in patients with chronic migraine (CM) using a data-driven method. METHODS: We prospectively recruited patients with either episodic migraine (EM) or CM aged 18-60 years who visited the headache clinic of the Samsung Medical Center from July 2016 to December 2017. All patients underwent 3 T MRI using an identical scanner. Patients were considered interictal if they did not have a migraine headache at the day and ± 1 days of functional MRI acquisition. Using the group-independent component analysis (ICA), connectivity analysis with a weighted and undirected network model was performed. The between-group differences in degree centrality (DC) values were assessed using 5000 permutation tests corrected with false discovery rate (FDR). RESULTS: A total of 62 patients (44 EM and 18 CM) were enrolled in this study. Among the seven functionally interpretable spatially independent components (ICs) identified, only one IC, interpreted as the pain matrix, showed a significant between-group difference in DC (CM > EM, p = 0.046). This association remained significant after adjustment for age, sex, migraine with aura (MWA), allodynia, depression, and anxiety (p = 0.038). The pain matrix was functionally correlated with the hypothalamus (p = 0.040, EM > CM) and dorsal raphe nucleus (p = 0.039, CM > EM) with different levels of strength in EM and CM. CONCLUSION: CM patients have a stronger connectivity in the pain matrix than do EM patients. Functional alteration of the pain network might play a role in migraine chronification.
Assuntos
Ansiedade/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Dor Crônica/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Transtornos de Enxaqueca/diagnóstico por imagem , Rede Nervosa/diagnóstico por imagem , Adulto , Ansiedade/fisiopatologia , Encéfalo/fisiopatologia , Dor Crônica/fisiopatologia , Depressão/diagnóstico por imagem , Depressão/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/fisiopatologia , Rede Nervosa/fisiopatologia , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: Coagulopathy is an important cause of stroke in cancer patients. However, underlying mechanisms and clinical factors related to coagulopathy remain unclear. We hypothesized that certain characteristics of cancer affect coagulopathy in patients with lung cancer and ischemic stroke. METHODS: Consecutive patients with active lung cancer and acute ischemic stroke were prospectively studied. Volume and pattern of acute brain infarcts and plasma levels of circulating tumor extracellular vesicles (EVs) were measured using flow cytometry. In vitro experiments investigated the pathophysiological mechanisms underlying cancer-associated coagulopathy. RESULTS: Of 114 patients, 95 (83.3%) had an adenocarcinoma cell type and 95 (83.3%) had distant metastasis. Acute brain infarct volumes were larger and circulating EV levels were higher in patients with an adenocarcinoma cell type than in those with other cell types. The presence of metastasis was not associated with infarct volume or circulating EV levels. Coagulation assays demonstrated dose-dependent shorter clotting times after treatment with EVs from adenocarcinoma cell lines than with the use of EVs from squamous cell carcinoma. These findings were confirmed by coagulation assays using circulating EVs from patients with adenocarcinoma and stroke and from those with conventional stroke mechanisms. CONCLUSIONS: Our findings indicate that cancer cell type is associated with circulating EV levels and coagulopathy in patients with lung cancer and stroke.
Assuntos
Adenocarcinoma de Pulmão/sangue , Carcinoma de Células Escamosas/sangue , Vesículas Extracelulares/metabolismo , Neoplasias Pulmonares/sangue , Acidente Vascular Cerebral/sangue , Trombofilia/sangue , Células A549 , Antígeno AC133/metabolismo , Adenocarcinoma de Pulmão/complicações , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Idoso , Antígenos CD/metabolismo , Caderinas/metabolismo , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Linhagem Celular Tumoral , Molécula de Adesão da Célula Epitelial/metabolismo , Feminino , Citometria de Fluxo , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/metabolismo , Trombofilia/complicações , Trombofilia/metabolismoRESUMO
OBJECTIVE: Diagnosis of reversible cerebral vasoconstriction syndrome (RCVS) is currently based on luminographic findings of vasoconstriction. In addition to vasoconstriction, the blood-brain barrier (BBB) breakdown has been postulated as a central mechanism of RCVS. Our aim was to document BBB breakdown in patients with RCVS and its role for the pathophysiology-based diagnosis of RCVS. METHODS: We prospectively recruited 72 consecutive patients with thunderclap headache who did not have aneurysmal subarachnoid hemorrhage from April 2015 to July 2016 at the Samsung Medical Center. Based on the International Classification of Headache Disorders-3 beta criteria and neuroimaging, patients were classified as having RCVS (n = 41; "definite" in 29 imaging-proven patients and "probable" in 12 imaging-negative patients), other secondary causes (n = 7), and thunderclap headache of undetermined cause (n = 24). BBB breakdown was evaluated using contrast-enhanced fluid-attenuated inversion recovery magnetic resonance imaging. RESULTS: BBB breakdown was documented in 20 (69.0%) patients with definite RCVS, 3 (25.0%) patients with probable RCVS, and none with other secondary causes. BBB breakdown was present in RCVS patients with (n = 4) and without (n = 19) concomitant posterior reversible encephalopathy syndrome. In patients with RCVS, the extent of BBB breakdown was independently associated with neurological complications (multivariate odds ratio = 1.48 per 1 territorial increase, 95% confidence interval = 1.04-2.12, adjusted p = 0.032). Three (12.5%) patients with thunderclap headache of undetermined cause were newly classified as having RCVS by the presence of BBB breakdown. INTERPRETATION: This is the first study to show BBB breakdown in patients with RCVS. This finding might broaden our understanding of the pathophysiology and clinical spectrum of RCVS. Ann Neurol 2017;81:454-466.
Assuntos
Barreira Hematoencefálica/diagnóstico por imagem , Doenças Arteriais Cerebrais/diagnóstico por imagem , Transtornos da Cefaleia Primários/diagnóstico por imagem , Síndrome da Leucoencefalopatia Posterior/diagnóstico por imagem , Vasoconstrição/fisiologia , Adulto , Doenças Arteriais Cerebrais/líquido cefalorraquidiano , Doenças Arteriais Cerebrais/epidemiologia , Doenças Arteriais Cerebrais/fisiopatologia , Comorbidade , Feminino , Transtornos da Cefaleia Primários/líquido cefalorraquidiano , Transtornos da Cefaleia Primários/epidemiologia , Transtornos da Cefaleia Primários/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome da Leucoencefalopatia Posterior/líquido cefalorraquidiano , Síndrome da Leucoencefalopatia Posterior/epidemiologia , Síndrome da Leucoencefalopatia Posterior/fisiopatologiaRESUMO
Objectives To serially test the International Classification of Headache Disorders (ICHD) 3rd edition beta version criteria for 6.7.3.1 probable reversible cerebral vasoconstriction syndrome (probable RCVS) in patients with thunderclap headache. Methods We prospectively screened consecutive patients with thunderclap headache who visited the Samsung Medical Center between October 2015 and March 2017. Patients were included in the analysis if they a) visited our hospital within 1 month after onset, b) completed a diagnostic work-up, and c) had no secondary causes other than RCVS. The ICHD-3 beta 6.7.3.1 criteria were evaluated serially during the first visit (visit 1), 2 weeks after the first visit (visit 2), and 1-3 months after onset (visit 3). Results A total of 99 patients completed this study. Based on the first clinical and radiological evaluation, 63 (63.6%) were diagnosed with angiogram-proven RCVS, whilst 36 (36.4%) showed normal neuroimaging. The ICHD-3 beta 6.7.3.1 criteria were fulfilled in 76.2% of patients with angiogram-proven RCVS. In patients with normal angiograms, the ICHD diagnosis of probable RCVS changed over time: 25.0%, 47.2%, and 38.9% at visits 1, 2, and 3, respectively. The sensitivity and specificity of the criteria at visit 1 were 72.4% and 95.5%, respectively, for the prediction of a final diagnosis of overall (angiogram-proven + probable) RCVS. Conclusions The ICHD-3 beta criteria for probable RCVS are applicable for patients with thunderclap headaches at the acute stage, with the exception of criterion C3. Criteria C1 and C2 are less reliable when applied at the first visit. Repeated evaluation is necessary to enhance diagnostic sensitivity.
Assuntos
Transtornos da Cefaleia Primários/etiologia , Vasoespasmo Intracraniano/diagnóstico , Adulto , Angiografia Cerebral , Feminino , Humanos , Classificação Internacional de Doenças , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Vasoespasmo Intracraniano/complicaçõesRESUMO
Background Intraorbital lesions associated with symptomatic trigeminal autonomic cephalalgias (TACs) are rarely reported. We present a case of orbital metastatic leiomyosarcoma, presenting with chronic paroxysmal hemicrania-like headache. Case report A 43-year-old man presented with a severe paroxysmal headache in his left periocular and frontal area for a year. The attacks occurred 10-12 times per day, lasting 10-15 minutes with ipsilateral lacrimation and conjunctival injection. Neurological examination and brain MRI without contrast were unremarkable. Different medications were tried, without beneficial effects. A follow-up contrast-enhanced brain MRI performed one year after the baseline MRI revealed an enhancing mass in the left superior oblique muscle. Orbital metastatic leiomyosarcoma arising from the thigh was revealed. He received gamma knife surgery, which completely resolved the headache. Discussion Intraorbital lesion should be considered a possibility in patients with headache mimicking TACs. Baseline contrast-enhanced MRI is essential, and repeated MRI scans might be needed if clinically indicated.
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Leiomiossarcoma/diagnóstico por imagem , Leiomiossarcoma/secundário , Neoplasias Orbitárias/diagnóstico por imagem , Neoplasias Orbitárias/secundário , Hemicrania Paroxística/diagnóstico por imagem , Adulto , Humanos , Leiomiossarcoma/complicações , Masculino , Neoplasias Orbitárias/complicações , Hemicrania Paroxística/etiologiaRESUMO
Objectives To report demographics and characteristics of reversible cerebral vasoconstriction syndrome (RCVS) in the Korean cohort. Methods We prospectively recruited patients with definite (imaging-proven) RCVS and probable (imaging-negative) RCVS who visited Samsung Medical Center between June 2012 and September 2016. Clinical manifestations, neuroimaging, treatment, and clinical outcomes were evaluated in all patients. Characteristics of RCVS without typical causes ("idiopathic RCVS") were compared with those of RCVS with identifiable causes ("secondary RCVS"). International Classification of Headache Disorders (ICHD)-3 beta criteria for 6.7.3 RCVS and 6.7.3.1 probable RCVS were tested. Results A total of 138 patients (104 definite and 34 probable RCVS) were included in this study. Patients with definite RCVS were predominantly female (85.6%) and middle-aged (mean, 50.7 [range, 23-82] years). Probable RCVS was associated with less female predominance (70.6%, p = 0.049), more typical manifestations ( p < 0.001), and none of neurological complications. One-hundred and one (97.1%) patients with definite RCVS had headache, but the typical "recurrent and/or triggered" thunderclap headache was reported in only 83 (82.2%). In most patients with definite RCVS (84.6%), RCVS was idiopathic, while only 16 (15.4%) had secondary causes. Compared to those with secondary RCVS, patients with idiopathic RCVS were older (52.8 ± 11.42 vs. 39.1 ± 9.55 years, p < 0.001). Patients with secondary RCVS had more complications than those with idiopathic RCVS (40.5% vs. 12.5%, p = 0.018). Among idiopathic RCVS patients, 33 (37.5%) reported a preceding event or a change in lifestyle, environment, health, or medication within one month before onset. Conclusion In our cohort, RCVS was benign and idiopathic in most patients, and occurred frequently in middle-aged women. Manifestations of RCVS were more diverse than previously recognized, and forms without any headache existed. Different genetic, social, and environmental factors should be taken into account to unveil the spectrum and pathophysiology of RCVS.
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Vasoespasmo Intracraniano , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Coreia (Geográfico) , Masculino , Pessoa de Meia-Idade , Síndrome , Vasoespasmo Intracraniano/epidemiologia , Vasoespasmo Intracraniano/etiologia , Vasoespasmo Intracraniano/patologia , Adulto JovemRESUMO
Objective To determine the natural course of cluster headache. Methods We screened patients with cluster headache who were diagnosed at Samsung Medical Center and lost to follow-up for ≥5 years. Eligible patients were interviewed by phone about the longitudinal changes in headache characteristics and disease course. Remission was defined as symptom-free 1) for longer than twice the longest between-bout period and 2) for ≥5 years. Results Forty-two patients lost to follow-up for mean 7.5 (range, 5.0-15.7) years were included. The length of the last bout did not differ from the first one, while the last between-bout period was longer than the first one ( p = 0.012). Characteristics of cluster headache decreased over time: Side-locked unilaterality (from 92.9% to 78.9%), seasonal and circadian rhythmicity (from 63.9% to 60.9% and from 62.2 to 40.5%, respectively), and autonomic symptoms (from 95.2% to 75.0%). Remission occurred in 14 (33.3%) patients at a mean age of 42.3 (range, 27-65) years, which was not different from the age of last bouts in active patients ( p = 0.623). There was a trend for more seasonal and circadian predilection at baseline in the active group ( p = 0.056 and 0.063, respectively) and fewer lifetime bouts and shorter disease duration in patients in remission ( p = 0.063 and 0.090). Conclusions This study first shows the natural courses of cluster headache. Features of cluster headache become less prominent over time. Remission occurred regardless of age. Although no single predictor of remission was found, our data suggest that remission of cluster headache might not be a consequence of more advanced age, longer duration of disease, or accumulation of lifetime bouts.
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Cefaleia Histamínica , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
Background Intracranial structural dislocation in spontaneous intracranial hypotension (SIH) can be measured by various intracranial angles and distances. We aimed to identify the clinical significance of structural dislocation in relation to treatment outcome in patients with SIH. Methods In this retrospective analysis, we identified patients with SIH who received an epidural blood patch (EBP) at Samsung Medical Center from January 2005 to March 2015. Structural dislocation in pretreatment MRIs of SIH patients was assessed by measuring tonsillar herniation, mamillopontine distance, the angle between the vein of Galen and straight sinus (vG/SS angle), the pontomesencephalic angle, and the lateral ventricular angle. After the first EBP, poor response was defined as the persistence of symptoms that prompted a repeat EBP. Results Out of the 95 patients included, 31 (32.6%) showed poor response. Among the radiological markers of structural dislocation, the vG/SS angle was associated with poor response (49.82 ± 16.40° vs 66.58 ± 26.08°, p = 0.002). Among clinical variables, premorbid migraine ( p = 0.036) was related to poor response. In multivariate analysis, reduced vG/SS angle was independently associated with poor response (OR 1.04 [95% CI 1.01 - 1.07] per 1° decrease, p = 0.006). In 23 patients who underwent MRI after successful treatment, the vG/SS angle significantly increased after the EBP ( p < 0.001, by paired t-test), while two patients with aggravation or recurrence showed a further reduction of their vG/SS angles. Conclusions Intracranial structural dislocation, measured by the vG/SS angle, is associated with poor response to the first EBP in patients with SIH. Successful treatment can reverse the structural dislocation.