Hypnic Headache - What do we know in 2022?

BACKGROUND: Hypnic Headache, also known as "alarm clock headache", is a rare primary headache disorder. It is characterized by frequently recurring headache attacks, which only develop during sleep, especially nighttime sleep. OBJECTIVE: This article gives a narrative review on the current knowledge about Hypnic Headache with a focus on secondary Hypnic Headache. METHODS: Based on literature research, using Pubmed and Google Scholar, latest case reports, studies, and systematic reviews about Hypnic Headache were analyzed and summarized focusing on therapeutic options and causes of secondary Hypnic Headache. CONCLUSION: Hypnic Headache mainly occurs in elderly patients. However, younger patients and children may also suffer from Hypnic Headache. Many different causes of secondary Hypnic Headache are described in the literature and ought to be ruled out before diagnosing primary Hypnic Headache. The pathophysiology of primary Hypnic Headache remains unclear, but a dysfunction of the hypothalamus seems to play a key role.

Comorbidity or combination - more evidence for cluster-migraine?

BACKGROUND: While migraine and cluster headache share some clinical features and therapies, they differ considerably in the frequency and duration of the headache, as well as the inter-attack, or inter-bout, pathophysiology. Neither is fully understood, with their shared pathways being of interest. FINDINGS: Five patients for whom it was difficult to distinguish migraine from cluster headache are presented. They had aspects of their phenotypes, which could be attributed to both disorders. Each patient was thoroughly examined, excluding secondary causes of headache, and had been treated with a number of medicines. CONCLUSION: A correct diagnosis is key to the appropriate treatment approach. Especially, if treatment is not successful for the suspected headache type, and enlargement of the diagnostic and therapeutic range, respectively, should be evaluated. Whether in such settings there is shared or different pathophysiology can only be speculated upon.

Defining migraine days, based on longitudinal E-diary data.

BACKGROUND: There is a need for standardization of the definition of a migraine day for clinical and research purposes. METHODS: We prospectively compared different definitions of a migraine day with E-diary data of n = 1494 patients with migraine. We used a baseline definition based on migraine characteristics with a duration of ≥4 hours OR triptan intake (independently from its effect) OR (visual) aura lasting 5-60 minutes. RESULTS: Of all migraine days defined by triptan intake only, 66.2% had a duration <4 hours. Adjusting the headache duration criterion to ≥30 minutes led to a decrease in days defined by triptan intake only and resulted in a 5.4% increase in total migraine days (equals 0.45 migraine day increase in monthly migraine days). These additional migraine days had a median duration of 2.5 hours. CONCLUSION: We propose to define a migraine day as follows: 1) (a) headache duration ≥30 minutes; (b) matching ≥2 of four characteristics: unilateral, pulsating, moderate to severe pain, aggravation by or causing avoidance of routine physical activity; and (c) during headache ≥1 of the following: nausea and/or vomiting, photophobia and phonophobia or 2) (visual) aura duration 5-60 minutes or 3) a day with headache for which acute migraine-specific medication is used irrespective of its effect.

Evaluation of the ICHD-3 diagnostic criteria for cardiac cephalalgia and new proposal.

BACKGROUND: The current International Classification of Headache Disorders, 3rd edition (ICHD-3) diagnostic criteria for cardiac cephalalgia were established according to previous case reports and the opinion of experts. We aimed to assess the ICHD-3 diagnostic criteria for cardiac cephalalgia. METHODS: We conducted a series of cases study and evaluated these criteria in 54 patients with cardiac cephalalgia. Next, we assessed whether the ICHD-3 diagnostic criteria B, C and D for migraine without aura were fulfilled by these patients. RESULTS: ICHD-3 criteria A, B, C1, C2 and D for cardiac cephalalgia were met by 100% of patients, whereas criterion C3 was fulfilled by 81.5%. The least frequently fulfilled sub-criterion was C3b (accompanied by nausea) (18.5%). Moreover, we found that ICHD-3 criteria B, C and D for migraine without aura were met by a low proportion of patients: 11.1%, 46.3% and 25.9%, respectively, and no patient fulfilled the three criteria simultaneously. CONCLUSION: Based on our results, we propose revised diagnostic criteria for cardiac cephalalgia. We suggest removing criterion C3 and C4. We also suggest removing the word "migraine-like" from its description.

A case report on recurrent alternating Tolosa-Hunt syndrome due to bacterial sphenoid sinusitis: rediscussing the diagnostic terminology and classification.

BACKGROUND: Tolosa-Hunt syndrome (THS) is characterized by painful ophthalmoplegia caused by idiopathic granulomatous inflammation involving the cavernous sinus region. Patients respond well to steroid therapy. THS is included in the differential diagnosis of cavernous sinus syndrome, so it is important to fully exclude other lesions in this area before treatment, otherwise steroid treatment may lead to fatal outcomes. Here we describe a patient who initially presented with symptoms that simulated THS symptoms and developed recurrent alternating painful ophthalmoplegia during follow-up, and the patient was finally diagnosed with cavernous sinusitis caused by bacterial sphenoid sinusitis. CASE PRESENTATION: A 34-year-old woman presented with left painful ophthalmoplegia. Magnetic resonance imaging (MRI) revealed abnormal signals in the left cavernous sinus area, and these abnormal signals were suspected to be THS. After steroid treatment, the patient obtained pain relief and had complete recovery of her ophthalmoplegia. However, right painful ophthalmoplegia appeared during the follow-up period. MRI showed obvious inflammatory signals in the right cavernous sinus and right sphenoid sinus. Then nasal sinus puncture and aspiration culture were performed, and the results showed a coagulase-negative staphylococcus infection. After antibiotic treatment with vancomycin, the painful ophthalmoplegia completely resolved, and the neurological examination and MRI returned to normal. CONCLUSION: Some other causes of painful ophthalmoplegia also fulfill the diagnostic criteria for THS in the International Classification of Headache Disorders third edition (ICHD-3) and respond well to steroid therapy. Early diagnosis of THS may be harmful to patients, and clinicians should exercise great caution when dealing with similar cases without a biopsy. Using "cavernous sinus syndrome" instead of "Tolosa-Hunt syndrome" as a diagnostic category may provide a better clinical thinking for etiological diagnosis.

Acute confusional state in HaNDL syndrome.

OBJECTIVE: To assess epidemiological, clinical and neuroimaging features of acute confusional state in the Headache and Neurological Deficits with cerebrospinal fluid Lymphocytosis (HaNDL) syndrome. BACKGROUND: HaNDL is an increasingly recognized syndrome in which migraine-like headache episodes accompanied by hemiparaesthesia and/or hemiparesis and/or dysphasia are associated to CSF lymphocytic pleocytosis. The International Classification of Headache Disorders (ICHD-3) includes HaNDL syndrome in group 7 "headache attributed to non-vascular intracranial disorder" code 7.3.5, and lists the HaNDL-associated signs/symptoms that may be found less frequently. Confusional state is not mentioned in the 7.3.5-ICHD-3 "notes" or "comments" section as part of the HaNDL neurological spectrum. Moreover, the acute confusional state pathogenesis in HaNDL syndrome remains still uncertain and debated. METHODS: Here, we report a 32-year-old male who complained episodes of migraine-like headache and left hemiparaesthesia complicated by confusional state which led to discovering CSF lymphocytosis. Since other workup to determine the cause of his symptoms was otherwise negative, he was diagnosed as having HaNDL syndrome. We also ascertained and reviewed all available reports of HaNDL to assess the significance of confusional state in this syndrome. RESULTS: The search yielded 159 HaNDL cases among single reports and small/large series. Out of 159 patients who fulfilled the inclusion criteria for HaNDL according to the current ICHD at the time of diagnosis, 41 (25.7%) presented with acute confusional state. Among 41 HaNDL patients with confusional state, 16 (66.6%) out of 24 who underwent spinal tap had increased opening pressure. CONCLUSION: We propose that a mention of acute confusional state may be included in the "comments" section of "7.3.5-syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL)," when ICHD-3 diagnostic criteria will be updated. Moreover, we speculate that intracranial hypertension may play a role in the pathogenesis of the acute confusional state associated to HaNDL syndrome. Larger case series are needed to evaluate this hypothesis.

The applicability research of the diagnostic criteria for 10.2 Heamodialysis-related headache in the international classification of headache disorders-3rd edition.

BACKGROUND: Headache during hemodialysis (HDH) is prevalent but not negligible. Despite the high prevalence of dialysis headaches, they have rarely been studied. Therefore, this study aimed to evaluate the prevalence, risk factors, and clinical characteristics of HDH and reappraise the HDH diagnostic criteria in the International Classification of Headache Disorders 3 (ICHD-3). METHODS: One hundred and fifty-four patients completed this randomized cross-sectional study. Consecutive patients who underwent haemodialysis were assessed using a semi-structured questionnaire. The patients were administered face-to-face questionnaires while undergoing dialysis. RESULTS: This study included 154 patients. Before commencing dialysis, 3.24% (5/154) of the patients had migraine without aura, 1.29% (2/154) had menstrual-related migraine, 0.6% (1/154) had tension-type headaches, and 0.6% (1/154) had an unclassifiable headache. One case (0.6%) of headache resolved after dialysis treatment. HDH was diagnosed in 9.09% (14/154) of the patients. Headache after haemodialysis (HAH) was reported in 6.49% (10/154) of patients. The most prevalent features of HDH were frontal or temporal location, bilateral headaches, dull and throbbing nature, and moderate severity. HDH started at a mean of 2.33 ± 0.79 h after dialysis commenced. The average headache duration was 6.56 ± 1.57 h (median = 3.0 h), with 66.67% of the patients reporting a duration of ≤4 h. HDH was more prevalent in females than males (P = 0.01, P < 0.05). Female sex was a risk factor for HDH (P = 0.01，P < 0.05). CONCLUSIONS: The diagnostic criteria for 10.2 HDH in ICHD-3 may miss several HAH. Therefore, ICHD-3 should be revised according to the literature and further studies.

Migraine symptoms, healthcare resources utilization and disease burden in a large Polish migraine cohort : Results from 'Migraine in Poland'-a nationwide cross-sectional survey.

BACKGROUND: The Migraine in Poland study is the first large scale nationwide cross-sectional online survey of symptoms, approaches to management, treatment patterns, quality of life, and sociodemographic characteristics of the Polish migraine patients' cohort, conducted from August 2021 to June 2022. METHODS: A cross-sectional online survey was designed based on the American Migraine Prevalence and Prevention (AMPP) Study. Participants were recruited through broad advertisement through various channels. The survey included questions allowing for the diagnosis of migraine without aura (MwoA) based on the third edition of the International Classification of Headache Disorders (ICHD-3). Moreover, the questionnaire assessed sociodemographic and headache features, comorbidities, consultation rates with medical professionals, as well as the use of abortive or preventive treatment, including non-pharmacological methods, psychological symptoms and the burden of migraine. RESULTS: A structured online questionnaire was submitted by 3225 respondents aged 13 to 80 (mean age 38.9, 87.1% women). In this group 1679 (52.7%) of participants fulfilled ICHD-3 diagnostic criteria for MwoA, which was in most cases (88.3%) confirmed by a medical professional in the past. In this group the average number of monthly headache days was 4.7, while 47.8% of participants had at least 4 migraine days per month. Mean Migraine Disability Assessment score was 42.65 (median 32). Among MwoA respondents, 1571 (93.6%) had consulted their headache with a medical professional in the past - mostly neurologists (n = 1450 (83.4%) and primary care physicians (n = 1393 (82.9%). In the MwoA cohort, 1553 (92.5%) of participants declared the current use of some form of treatment, although only 193 (11.5%) respondents were currently on preventive medications. The most prevalent comorbidities included: chronic rhinitis (37.1%), allergies (35.9%) and low blood pressure (26.9%). Anxiety (20.4%) and depression (21.3%) were highly prevalent among participants. CONCLUSIONS: People with migraine in Poland face similar difficulties as their peers in other countries. Despite relatively high access to neurologist consultations and good diagnosis accuracy, migraine still poses diagnostic and therapeutic difficulties. In this context, migraine undertreatment in Polish population must be underlined, especially in context of high disease burden.

Cross-sectional, hospital-based analysis of headache types using ICHD-3 criteria in the Middle East, Asia, and Africa: the Head-MENAA study.

BACKGROUND: Headaches are frequent neurological disorders that are yet to be unveiled and treated comprehensively worldwide. Bearing in mind that the distribution of headache subtypes in neurology clinics (NC) is essential for planning appropriate diagnostic and therapeutic approaches, the primary goals of this multi-centric study are to carry out inter-regional comparisons by using current diagnostic criteria with evaluations of neurologists to delineate headache burden. METHODS: A cross-sectional study between April 1 and May 16, 2022 was conducted with the participation of 13 countries from the Middle East, Asia, and Africa. Patients were included in the study on a specific day each week during five consecutive weeks. All volunteers over the age of 18 and whose primary cause for admission was headache were examined. The patients admitted to NC or referred from emergency services/other services were evaluated by neurologists by means of the International Classification of Headache Disorders (ICHD-3) criteria. RESULTS: Among the 13,794 patients encountered in NC, headache was the primary complaint in 30.04%. The headache patients' mean age was 42.85 ± 14.89 (18-95 years), and 74.3% were female. According to the ICHD-3 criteria, 86.7% of the main group had primary headache disorders, 33.5% had secondary headaches, 4% had painful cranial neuropathies along with other facial and headaches, and 5.2% had headaches included in the appendix part showing some overlapping conditions. While the most common primary headache was migraine without aura (36.8%), the most common secondary headache was medication-overuse headache (MOH) (9.8%). Headaches attributed to COVID-19, its secondary complications, or vaccines continue to occur at rates of 1.2%-3.5% in current neurology practice. Pain severity was significantly lower in Ivory Coast and Sudan than in Türkiye, Turkish Republic of Northern Cyprus, Iran, Egypt, Senegal, Tatarstan, and Azerbaijan (p < 0.001). CONCLUSIONS: The study showed that migraine is still the most common motive for admissions to NC in different regions. Furthermore, MOH, an avoidable disorder, is the most common secondary headache type and appears to be a significant problem in all regions. Remarkably, pain perception differs between regions, and pain intensity is lower in Africa than in other regions.

Guidelines of the International Headache Society for Controlled Clinical Trials in Cluster Headache.

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.

Validation of diagnostic ICHD-3 criteria for menstrual migraine.

OBJECTIVE: To assess validity of ICHD-3 diagnostic criteria for menstrual migraine. METHODS: We performed a longitudinal E-diary study in premenopausal women with migraine. Menstrual migraine diagnosis was self-reported at baseline, and verified according to diary based ICHD-3 criteria and a previous proposed statistical model. Validity of self-reported menstrual migraine was compared to diary based diagnosis and statistical diagnosis. Test-retest reliability and concordance between both methods were determined. Clinical characteristics of perimenstrual and non-perimenstrual migraine attacks were compared in women with and without menstrual migraine. RESULTS: We included 607 women. Both women who did and women who did not self-report to suffer from menstrual migraine fulfilled ICHD-3 criteria in the E-diary in two thirds of cases. Pure menstrual migraine was extremely rare (<1%). Concordance between statistical and diary based diagnosis was minimal (κ = 0.28, 95% CI:0.23-0.33). Women diagnosed with menstrual migraine showed 37-50% longer attack duration and increased triptan intake (OR 1.19-1.22, p < 0.001) during perimenstrual attacks. CONCLUSION: Self-reported menstrual migraine diagnosis has extremely poor accuracy. Two thirds of women suffer from menstrual migraine, independent of self-reports. Pure menstrual migraine is rare. Women with menstrual migraine have longer attack duration and increased triptan intake during perimenstrual attacks, in contrast to women without menstrual migraine. Prospective headache (E-)diaries are required for a menstrual migraine diagnosis, also in clinical practice.

Revisiting the ICHD-3 criteria for headache attributed to mild traumatic injury to the head: Insights from the Toronto Concussion Study Analysis of Acute Headaches Following Concussion.

BACKGROUND: There is limited prospective data on the prevalence, timing of onset, and characteristics of acute headache following concussion/mild traumatic brain injury. METHODS: Adults diagnosed with concussion (arising from injuries not related to work or motor vehicle accidents) were recruited from emergency departments and seen within one week post injury wherein they completed questionnaires assessing demographic variables, pre-injury headache history, post-injury headache history, and the Sport Concussion Assessment Tool (SCAT-3) symptom checklist, the Sleep and Concussion Questionnaire (SCQ) and mood/anxiety on the Brief Symptom Inventory (BSI). RESULTS: A total of 302 participants (59% female) were enrolled (mean age 33.6 years) and almost all (92%) endorsed post-traumatic headache (PTH) with 94% endorsing headache onset within 24 hours of injury. Headache location was not correlated with site of injury. Most participants (84%) experienced daily headache. Headache quality was pressure/squeezing in 69% and throbbing/pulsing type in 22%. Associated symptoms included: photophobia (74%), phonophobia (72%) and nausea (55%). SCAT-3 symptom scores, Brief Symptom Inventory and Sleep and Concussion Questionnaire scores were significantly higher in those endorsing acute PTH. No significant differences were found in week 1 acute PTH by sex, history of migraine, pre-injury headache frequency, anxiety, or depression, nor presence/absence of post-traumatic amnesia and self-reported loss of consciousness. CONCLUSIONS: This study highlights the very high incidence of acute PTH following concussion, the timing of onset and characteristics of acute PTH, the associated psychological and sleep disturbances and notes that the current ICHD-3 criteria for headaches attributed to mild traumatic injury to the head are reasonable, the interval between injury and headache onset should not be extended beyond seven days and could, potentially, be shorted to allow for greater diagnostic precision.

Characteristics of headache during and/or after coronary intervention: A prospective observational study.

INTRODUCTION: Headache during and/or after coronary intervention is common but has received little attention from cardiologists and neurologists. The purpose of this study was to investigate the incidence, risk factors, and possible mechanism of coronary intervention-related headache. METHODS: Using a prospective observational design, we identified consecutive patients with coronary intervention from May 2020 to August 2020. Patients were followed up with questionnaires immediately after coronary intervention and 24 h, 72 h, 1 week and 2 weeks after the intervention. RESULTS: In total, 94 patients were enrolled, and 71 patients ultimately completed the 2-week follow-up. Among 71 patients, headache developed during and/or after coronary intervention in 18 (25.4%) patients. Two different types of headache related to coronary intervention were observed: One during and another after coronary intervention. Headache characteristics are described in detail. A history of previous headache was an independent risk factor for coronary intervention-related headache (p < 0.01). CONCLUSIONS: Coronary intervention-related headache has an incidence of 25.4%, and previous headache history was an independent risk factor. Moreover, considering that there are no relevant diagnostic criteria, it is suggested that the definition of coronary intervention-related headache should be established in the International Classification of Headache Disorders.

De novo headache in ischemic stroke patients treated with thrombectomy: a prospective study.

BACKGROUND AND AIM: Headache attributed to intracranial endovascular procedures is described in the ICHD-3. Our aim was to study the frequency and characteristics of headache specifically related to thrombectomy in patients with ischemic stroke. METHODS: Prospective evaluation of clinical features of headache after thrombectomy using an ad hoc questionnaire. RESULTS: One hundred seventeen patients were included (52.1% females). Most had an anterior circulation artery occlusion (91.5%). 93 (79.5%) received general anaesthesia. 111 (94.9%) required stent retriever, 21 (24.4%) angioplasty and 19 (16.2%) aspiration thrombectomy. 31 (26.5%; 95% CI 18.8-35.5%) had headache related to thrombectomy, and it was associated with a history of primary headache (p = 0.004). No differences about sex, initial NIHSS score, or the type or complexity of the procedure were observed. Headache was usually moderate and oppressive, ipsilateral to the artery occlusion and usually lasted less than 48 hours. CONCLUSIONS: Almost one-third of patients with ischemic stroke who undergo endovascular thrombectomy experience headache in the first 24 hours, occurring more frequently in patients who had a previous history of headaches regardless of the procedure complexity.

The applicability research of the diagnostic criteria for 6.7.2 angiography headache in the international classification of headache disorders-3rd edition.

BACKGROUND: Angiography headache (AH) is common but not negligible, and the criteria for AH have been based on only a few studies. The purpose of this study was to investigate the incidence, risk factors and possible mechanism of AH and reappraise the diagnostic criteria for AH in the International Classification of Headache Disorders 3 (ICHD-3). METHODS: Two hundred and seventy-nine patients completed this prospective, non-randomized study, including 107 patients who underwent cerebral angiography, 101 patients who underwent coronary intervention and 71 patients who underwent extremities arterial intervention. Patients were followed up with questionnaires immediately after the procedure and 24 h, 72 h, 1 week and 2 weeks after the procedure. RESULTS: The incidence of headache was 22.4% (24/107) in cerebral angiography group, 23.8% (24/101) in coronary intervention group, and 16.9% (12/71) in extremities arterial intervention group. Headache still occurred in 12.1% (13/107), 14.9% (15/101) and 11.3% (8/71) of patients 24 h after the procedure in the three groups, respectively. Two types of headache were observed in cerebral angiography group and coronary intervention group, one during and one after the procedure, while only postoperative headache was observed in extremities arterial intervention group. Previous headache history was a risk factor for headache in the three groups (p = 0.003 in cerebral angiography group, p = 0.006 in coronary intervention group, and p = 0.016 in extremities arterial intervention group). In addition, female (p = 0.008) was a risk factor for cerebral angiography group. Headache characteristics were described in detail. CONCLUSIONS: The diagnostic criteria for 6.7.2 angiography headache in ICHD-3 may miss a number of cerebral AH with onset later than 24 h after the procedure. Therefore, it is recommended to revise it according to the literature and further studies. The incidence of headache was high during and after angiography and interventional procedure. It was suggested that the definition of headache due to coronary intervention and headache due to extremities arterial intervention should be added in ICHD.

Diagnosis and classification of headache associated with sexual activity using a composite algorithm: A cohort study.

BACKGROUND: To differentiate primary headache associated with sexual activity from other devastating secondary causes. METHODS: In this prospective cohort, we recruited consecutive patients with at least 2 attacks of headache associated with sexual activity from the headache clinics or emergency department of a national medical center from 2005 to 2020. Detailed interview, neurological examination, and serial thorough neuroimaging including brain magnetic resonance imaging and magnetic resonance angiography scans were performed on registration and during follow-ups. Patients were categorized into four groups, i.e. primary headache associated with sexual activity, reversible cerebral vasoconstriction syndrome, probable reversible cerebral vasoconstriction syndrome, and other secondary headache associated with sexual activity through a composite clinic-radiological diagnostic algorithm. We compared the clinical profiles among these groups, including sex, age of onset, duration, quality, and clinical course ("chronic" indicates disease course ≥ 1 year). In addition, we also calculated the score of the reversible cerebral vasoconstriction syndrome2, a scale developed to differentiate reversible cerebral vasoconstriction syndrome from other intracranial vascular disorders. RESULTS: Overall, 245 patients with headache associated with sexual activity were enrolled. Our clinic-radiologic composite algorithm diagnosed and classified all patients into four groups, including 38 (15.5%) with primary headache associated with sexual activity, 174 (71.0%) with reversible cerebral vasoconstriction syndrome, 26 (10.6%) with probable reversible cerebral vasoconstriction syndrome, and 7 (2.9%) with other secondary causes (aneurysmal subarachnoid hemorrhage (n = 4), right internal carotid artery dissection (n = 1), Moyamoya disease (n = 1), and meningioma with hemorrhage (n = 1)). These four groups shared similar clinical profiles, except 26% of the patients with primary headache associated with sexual activity had a 3 times greater chance of running a chronic course (≥ 1 year) than patients with reversible cerebral vasoconstriction syndrome. Of note, the reversible cerebral vasoconstriction syndrome2 score could not differentiate reversible cerebral vasoconstriction syndrome from other groups. CONCLUSION: Our composite clinic-radiological diagnostic algorithm successfully classified repeated headaches associated with sexual activity, which were predominantly secondary and related to vascular disorders, and predicted the prognosis. Primary headache associated with sexual activity and reversible cerebral vasoconstriction syndrome presented with repeated attacks of headache associated with sexual activity may be of the same disease spectrum.

The clinical and public health implications and risks of widening the definition of chronic migraine.

BACKGROUND: The definition of chronic migraine has long been debated. Recently, it was suggested to define subjects with at least 8/migraine days as chronic migraine; that is, incorporating so-called high frequency episodic migraine (eight or more migraine days but less than 15 headache days per month). METHODS: We addressed the possible problems that might arise based on this proposal accounting for clinical, pathophysiological, impact and public health aspects. RESULTS AND CONCLUSIONS: Defining chronic migraine on the basis of headache frequency alone does not account for clinical and pathophysiological aspects, as well as for the impact of chronic migraine in terms of disability and quality of life. Moreover, it is potentially harmful for patients in terms of allocation of resources. These issues are discussed in the present manuscript, and we support the idea of defining high frequency episodic migraine as an independent entity as a viable path to follow.

Reason to doubt the ICHD-3 7-day inclusion criterion for mild TBI-related posttraumatic headache: A nested cohort study.

BACKGROUND: Posttraumatic headache is difficult to define and there is debate about the specificity of the 7-day headache onset criterion in the current definition. There is limited evidence available to guide decision making about this criterion. METHOD: A nested cohort study of 193 treatment-seeking veterans who met criteria for persistent headache attributed to mild traumatic injury to the head, including some veterans with delayed headache onset up to 90 days post-injury, was undertaken. Survival analysis examined the proportion of participants reporting headache over time and differences in these proportions based on sex, headache phenotype, and mechanism of injury. RESULT: 127 participants (66%; 95% CI: 59-72%) reported headache onset within 7 days of head injury and 65 (34%) reported headache onset between 8 days and 3 months after head injury. Fourteen percent of participants reported pre-existing migraine before head injury, and there was no difference in the proportion of veterans with pre-existing migraine based on headache onset. Headache onset times were not associated with sex, headache phenotype, or mechanism of injury. There were no significant differences in proportion of veterans with headache onset within 7 days of head injury based on headache phenotype (70% migraine onset within 7 days, 70% tension-type headache within 7 days, 56% cluster headache within 7 days; p ≥ .364). Similar findings were observed for head injury (64% blast, 60% blunt; p = .973). There were no significant differences observed between headache onset groups for psychiatric symptoms (Posttraumatic Stress Disorder Checklist for DSM-5 = 1.3, 95% CI = -27.5, 30.1; Patient Health Questionnaire-9 Item = 3.5, 95% CI = -6.3, 3.7; Generalized Anxiety Disorder Screener = 6.5, 95% CI = -2.7, 15.6). CONCLUSIONS: Although most of the sample reported headache onset within 7 days of head injury, one-third experienced an onset outside of the diagnostic range. Additionally, veterans with headache onset within 7 days of head injury were not meaningfully different from those with later onset based on sex, headache phenotype, or mechanism of head injury. The ICHD-3 diagnostic criteria for 7-day headache onset should be expanded to 3 months. CLINICALTRIALS.GOV IDENTIFIER: NCT02419131.

ICHD-3 is significantly more specific than ICHD-3 beta for diagnosis of migraine with aura and with typical aura.

BACKGROUND: In the emergency room, distinguishing between a migraine with aura and a transient ischemic attack (TIA) is often not straightforward and mistakes can be harmful to both the patient and to society. To account for this difficulty, the third edition of the International Classification of Headache disorders (ICHD-3) changed the diagnostic criteria of migraine with aura. METHODS: One hundred twenty-eight patients referred to the emergency room at the University Hospital of Lübeck, Germany with a suspected TIA were prospectively interviewed about their symptoms leading to admission shortly after initial presentation. The diagnosis that resulted from applying the ICHD-3 and ICHD-3 beta diagnostic criteria was compared to the diagnosis made independently by the treating physicians performing the usual diagnostic work-up. RESULTS: The new ICHD-3 diagnostic criteria for migraine with aura and migraine with typical aura display an excellent specificity (96 and 98% respectively), and are significantly more specific than the previous ICHD-3 beta classification system when it comes to diagnosing a first single attack (probable migraine with aura and probable migraine with typical aura). CONCLUSIONS: The ICHD-3 is a highly useful tool for the clinical neurologist in order to distinguish between a migraine with aura and a TIA, already at the first point of patient contact, such as in the emergency department or a TIA clinic.

A prospective study of headache and neuropeptides in patients with pituitary adenomas.

OBJECTIVE: To evaluate clinical criteria for headache associated with pituitary adenoma (HaPA) in the International Classification of Headache Disorders (ICHD) 3rd edition version criteria and further determine whether elevations of plasma calcitonin gene-related peptide and pituitary adenylate cyclase-activating peptide 1-38 (PACAP1-38) concentration contribute to HaPA. METHODS: Demographic and clinical features of consecutive patients with pituitary adenoma were recorded. Plasma calcitonin gene-related peptide and PACAP1-38 concentrations in pituitary adenoma patients within 72 h pre- and post-operation were measured. Primary outcome for HaPA patients were 50% reduction of moderate-to-severe headache days at 3 months after discharge. RESULTS: Sixty-three patients with pituitary adenoma were recruited, 33 (52.4%) of whom had headache. The patients who had HaPA presented with migraine-like (32.9%), tension-type-like (12.1%), and stabbing headache (9.1%). Non-functional adenoma was present in the majority of cases (82.5%). Surgical resection improved headache in 83.3% of cases at 3 month follow-up. Pre- and post-operative calcitonin gene-related peptide and PACAP1-38 levels were significantly higher in patients with headache than in those without headache (p < 0.05). Plasma calcitonin gene-related peptide and PACAP1-38 levels at 72 h post-operation were lower at 72 h after operation in patients who had greater improvement in headache compared with those who had little improvement, while plasma calcitonin gene-related peptide and PACAP1-38 levels were similar between these two groups preoperatively. CONCLUSIONS: Most pituitary adenoma patients have non-functional adenoma, and half of this group have HaPA, indicating that the ICHD-3 criteria for HaPA with the emphasis on secretion status need further modifications. Lower plasma calcitonin gene-related peptide and PACAP1-38 concentrations at 72 h after operation may predict a better outcome in patients with HaPA.