RESUMO
Compared with migraine and tension-type headache, trigeminal autonomic cephalgias (TAC) are rare, but the resulting significant impairment and the not irrelevant prevalence (e. g., cluster headache 0.1%) make TACs important diagnoses. Unfortunately, the correct diagnosis is often delayed. This article provides an overview of the diagnostic approach and therapeutic options in TACs.
Assuntos
Cefaleia Histamínica , Transtornos de Enxaqueca , Cefaleia do Tipo Tensional , Cefalalgias Autonômicas do Trigêmeo , Cefaleia , Humanos , Cefalalgias Autonômicas do Trigêmeo/diagnóstico , Cefalalgias Autonômicas do Trigêmeo/epidemiologia , Cefalalgias Autonômicas do Trigêmeo/terapiaRESUMO
INTRODUCTION: Wound healing disturbances as possible side effects of calcitonin gene-related peptide (CGRP) antibody treatment have been discussed previously but not yet described in humans. Basic research suggests that calcitonin gene-related peptide plays an important role in keratinocyte migration, vascularization and immune response and lack of calcitonin gene-related peptide may lead to impaired wound healing. CASE: A 51-year-old female migraine patient was treated with the CGRP receptor antibody erenumab for 6 months, which led to a relevant reduction of migraine days. During the treatment, two periods of severely impaired wound healing occurred after a trivial skin injury without spatial relation to the injection site. Skin biopsy confirmed a deep perivascular and interstitial lymphohistiocytic infiltrate with admixed eosinophils, ulceration of the epithelium, a heavy edema of the papillary dermis and focally thrombosed vessels. CONCLUSION: Impaired wound healing might be relevant side effects of CGRP antibody therapy and anamnesis within the course of treatment should also include possible observation of impaired wound healing or planned surgery.
Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/efeitos adversos , Transtornos de Enxaqueca/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
Epidemiological studies have shown a clear correlation between migraine and vascular disease in more and more patients. Pathophysiological studies show the relevance of the hypothalamus in the generation of migraine attacks. Glutamate seems to play an important role here. New contrast-enhanced MRI studies support the assumption that the blood-brain barrier remains intact during migraine attacks. The selection of a triptan still remains unique. Neurostimulation has also been included in the acute treatment of migraine. Monoclonal humanized antibodies against CGRP (calcitonin gene-related peptides) and a fully human antibody against the CGRP receptor are effective in the prophylaxis of both episodic and chronic migraine. Tricyclic antidepressants showed efficacy in tension-type headache and is superior compared to SSRIs (selective serotonin reuptake inhibitors). Electronic diaries can reduce the risk of relapse after a medication break in the event of overuse of headache medication. In patients with episodic cluster headache, successful transient therapy with transcutaneous stimulation of the vagus nerve may be required. In trigeminal neuralgia, a significant comorbidity with depression and anxiety disorders was found.
Assuntos
Cefaleia , Peptídeo Relacionado com Gene de Calcitonina , Humanos , Transtornos de EnxaquecaRESUMO
A review of the latest and most relevant information on different disorders of head and facial pain is presented. News from epidemiologic studies regarding the relationship between migraine and patent foramen ovale, the cardiovascular risk in migraine, and migraine behavior during menopause, and the development of white matter lesions or migraine genetics are presented. Regarding pathophysiology there are very recent insights regarding the role of the hypothalamus during prodromal phase and the interplay of brain-stem and hypothalamus during the attack. In the last year studies and metaanalysis generated new knowledge for the use of triptans in general as in menstrual related migraine and hemiplegic variants. Furthermore, new hope rises for the CGRP (calcitonin-gene related peptide)-antagonists, as the data for ubrogepant do not suggest hepatotoxicity but efficacy. In prophylactic migraine treatment the news are manly on how the new therapeutic approach with monoclonal antibodies against CGRP or its receptor is moving on. Additional newly generated data for already known prophylactic agents as for new approaches are compactly discussed. Although main developments in headache focus on migraine new data on trigemino-autonomic headache trigeminal neuralgia and new daily persistant headache became available.
Assuntos
Transtornos da Cefaleia/terapia , Cefaleia Histamínica/tratamento farmacológico , Cefaleia Histamínica/epidemiologia , Cefaleia Histamínica/genética , Transtornos da Cefaleia/epidemiologia , Transtornos da Cefaleia/genética , Transtornos da Cefaleia Secundários/epidemiologia , Transtornos da Cefaleia Secundários/genética , Transtornos da Cefaleia Secundários/terapia , Humanos , Transtornos de Enxaqueca/epidemiologia , Transtornos de Enxaqueca/genética , Transtornos de Enxaqueca/terapia , Prevalência , Cefaleia do Tipo Tensional/epidemiologia , Cefaleia do Tipo Tensional/genética , Cefaleia do Tipo Tensional/terapia , Cefalalgias Autonômicas do Trigêmeo/tratamento farmacológico , Cefalalgias Autonômicas do Trigêmeo/epidemiologia , Cefalalgias Autonômicas do Trigêmeo/genética , Neuralgia do Trigêmeo/epidemiologia , Neuralgia do Trigêmeo/genética , Neuralgia do Trigêmeo/terapiaRESUMO
BACKGROUND: Prednisone is commonly used for initial short-term therapy of episodic cluster headaches before preventive medication such as verapamil becomes effective, but this strategy has not been tested in large randomised trials. We aimed to access the safety and efficacy of this treatment approach. METHODS: This study was a multicentre, randomised, double-blind, placebo-controlled trial done in ten specialised headache centres in Germany. Patients with episodic cluster headaches who were aged between 18 and 65 years and within a current pain episode for not more than 30 days, received 100 mg oral prednisone for 5 days followed by tapering of 20 mg every 3 days, or matching placebo (17 days total exposure). All patients received oral verapamil for long-term prevention, starting with 40 mg three times daily and increasing to 120 mg three times daily by day 19; patients then continued with verapamil 120 mg throughout the study. Randomisation was computer-generated at a 1:1 ratio by use of an interactive web-response system, with stratification according to age, sex, and participating site. Participants, investigators, and those assessing outcomes were unaware of treatment allocation. The primary endpoint was the mean number of attacks within the first week of treatment with prednisone compared with placebo. An attack was defined as a unilateral headache with moderate-to-severe intensity of at least five on a numerical rating scale. All efficacy and safety analyses were done in the modified intention-to-treat (mITT) population, which consisted of all patients who had been randomly assigned to a trial group and received at least one dose of prednisone or placebo. The study was stopped early due to slow recruitment and expired funding. The study was registered with EudraCT (2011-006204-13) and with the German Clinical Trials Register (DRKS00004716). FINDINGS: Between April 5, 2013, and Jan 11, 2018, 118 patients were enrolled in the study. Two patients dropped out immediately and 116 patients were randomly assigned (57 patients to prednisone and 59 patients to placebo); 109 patients were included in the mITT analysis (53 patients assigned to prednisone and 56 patients assigned to placebo). Participants in the prednisone group had a mean of 7·1 (SD 6·5) attacks within the first week compared with 9·5 (6·0) attacks in the placebo group (difference -2·4 attacks, 95% CI -4·8 to -0·03; p=0·002). Two serious adverse events occurred, both in the placebo group (inguinal hernia and severe deterioration of cluster headache). A total of 270 adverse events were observed: in the prednisone group, 37 (71%) of 52 patients reported 135 adverse events (most common were headache, palpitations, dizziness, and nausea) and in the placebo group, 39 (71%) of 55 patients had 135 adverse events (most common were nausea, dizziness, and headache). INTERPRETATION: Oral prednisone was an effective short-term preventive therapy in our population of patients with episodic cluster headache. Our findings support the use of prednisone as a first-line treatment in parallel to the up-titration of verapamil, although the efficacy of prednisone alongside other long-term prevention requires additional investigation. FUNDING: German Federal Ministry for Education and Research.
Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Cefaleia Histamínica/prevenção & controle , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Glucocorticoides/farmacologia , Avaliação de Resultados em Cuidados de Saúde , Prednisona/farmacologia , Verapamil/farmacologia , Adulto , Bloqueadores dos Canais de Cálcio/administração & dosagem , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Verapamil/administração & dosagemRESUMO
Functional neuroimaging was able to identify key structures for the pathophysiology of trigeminal autonomic cephalalgias (TACs) including cluster headache, paroxysmal hemicrania, and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing or cranial autonomic features and hemicrania continua. The posterior hypothalamus was the structure most consistently depicted with functional imaging in different states of disease with and without pain. Network-oriented imaging techniques such as resting-state functional resonance imaging were able to show a broader involvement of human trigeminal pain processing in the underlying pathophysiological mechanisms of the different TACs, highlighting similarities between this distinct group of primary headache disorders, while also demonstrating the differences in brain activation across these disorders. The most important clinical assignment for neuroimaging research from the treating physician remains the objective and reliable distinction of each individual TAC syndrome from one another, to make the correct clinical diagnosis as the foundation for proper treatment. More research will be necessary to fulfill this unmet need.
RESUMO
A precondition for the successful treatment of headaches is the correct headache diagnosis. Triptans are effective for attack treatment of migraine and cluster headache. However, there are not effective for the treatment of tension-type headache. For the prevention of frequent episodic migraine betablockers, flunarizine, topiramate and amitriptyline are recommended. For the prevention of chronic migraine evidence is only available for onabotulinumtoxinA and topiramate. For prophylactic treatment of tension-type headaches tricyclic antidepressants are used. In cluster headache verapamil (in combination with steroids) is the most frequently used prophylactic agent. This article focusses on the current acute and prophylactic treatment of common headache syndromes.