European Headache Federation recommendations for neurologists managing giant cell arteritis.

BACKGROUND AND AIM: Giant cell arteritis (GCA) remains a medical emergency because of the risk of sudden irreversible sight loss and rarely stroke along with other complications. Because headache is one of the cardinal symptoms of cranial GCA, neurologists need to be up to date with the advances in investigation and management of this condition. The aim of this document by the European Headache Federation (EHF) is to provide an evidence-based and expert-based recommendations on GCA. METHODS: The working group identified relevant questions, performed systematic literature review and assessed the quality of available evidence, and wrote recommendations. Where there was not a high level of evidence, the multidisciplinary (neurology, ophthalmology and rheumatology) group recommended best practice based on their clinical experience. RESULTS: Across Europe, fast track pathways and the utility of advanced imaging techniques are helping to reduce diagnostic delay and uncertainty, with improved clinical outcomes for patients. GCA is treated with high dose glucocorticoids (GC) as a first line agent however long-term GC toxicity is one of the key concerns for clinicians and patients. The first phase 2 and phase 3 randomised controlled trials of Tocilizumab, an IL-6 receptor antagonist, have been published. It is now been approved as the first ever licensed drug to be used in GCA. CONCLUSION: The present article will outline recent advances made in the diagnosis and management of GCA.

Aids to management of headache disorders in primary care (2nd edition) : on behalf of the European Headache Federation and Lifting The Burden: the Global Campaign against Headache.

The Aids to Management are a product of the Global Campaign against Headache, a worldwide programme of action conducted in official relations with the World Health Organization. Developed in partnership with the European Headache Federation, they update the first edition published 11 years ago.The common headache disorders (migraine, tension-type headache and medication-overuse headache) are major causes of ill health. They should be managed in primary care, firstly because their management is generally not difficult, and secondly because they are so common. These Aids to Management, with the European principles of management of headache disorders in primary care as the core of their content, combine educational materials with practical management aids. They are supplemented by translation protocols, to ensure that translations are unchanged in meaning from the English-language originals.The Aids to Management may be individually downloaded and, as is the case for all products of the Global Campaign against Headache, are available without restriction for non-commercial use.

Headache service quality: the role of specialized headache centres within structured headache services, and suggested standards and criteria as centres of excellence.

In joint initiatives, the European Headache Federation and Lifting The Burden have described a model of structured headache services (with their basis in primary care), defined service quality in this context, and developed practical methods for its evaluation.Here, in a continuation of the service quality evaluation programme, we set out ten suggested role- and performance-defining standards for specialized headache centres operating as an integral component of these services. Verifiable criteria for evaluation accompany each standard. The purposes are five-fold: (i) to inspire and promote, or stimulate the establishment of, specialized headache centres as centres of excellence; (ii) to define the role of such centres within optimally structured and organized national headache services; (iii) to set out criteria by which such centres may be recognized as exemplary in their fulfilment of this role; (iv) to provide the basis for, and to initiate and motivate, collaboration and networking between such centres both nationally and internationally; (v) ultimately to improve the delivery and quality of health care for headache.

Nociception-specific blink reflex: pharmacology in healthy volunteers.

BACKGROUND: The physiology and pharmacology of activation or perception of activation of pain-coding trigeminovascular afferents in humans is fundamental to understanding the biology of headache and developing new treatments. METHODS: The blink reflex was elicited using a concentric electrode and recorded in four separate sessions, at baseline and two minutes after administration of ramped doses of diazepam (final dose 0.07 mg/kg), fentanyl (final dose 1.11 µg/kg), ketamine (final dose 0.084 mg/kg) and 0.9 % saline solution. The AUC (area under the curve, µV*ms) and the latency (ms) of the ipsi- and contralateral R2 component of the blink reflex were calculated by PC-based offline analysis. Immediately after each block of blink reflex recordings certain psychometric parameters were assessed. RESULTS: There was an effect due to DRUG on the ipsilateral (F 3,60 = 7.3, P < 0.001) AUC as well as on the contralateral (F 3,60 = 6.02, P < 0.001) AUC across the study. A significant decrement in comparison to placebo was observed only for diazepam, affecting the ipsilateral AUC. The scores of alertness, calmness, contentedness, reaction time and precision were not affected by the DRUG across the sessions. CONCLUSION: Previous studies suggest central, rather than peripheral changes in nociceptive trigeminal transmission in migraine. This study demonstrates a robust effect of benzodiazepine receptor modulation of the nociception specific blink reflex (nBR) without any µ-opiate or glutamate NMDA receptor component. The nociception specific blink reflex offers a reproducible, quantifiable method of assessment of trigeminal nociceptive system in humans that can be used to dissect pharmacology relevant to primary headache disorders.

European Headache Federation consensus on technical investigation for primary headache disorders.

The diagnosis of primary headache disorders is clinical and based on the diagnostic criteria of the International Headache Society (ICHD-3-beta). However several brain conditions may mimic primary headache disorders and laboratory investigation may be needed. This necessity occurs when the treating physician doubts for the primary origin of headache. Features that represent a warning for a possible underlying disorder causing the headache are new onset headache, change in previously stable headache pattern, headache that abruptly reaches the peak level, headache that changes with posture, headache awakening the patient, or precipitated by physical activity or Valsalva manoeuvre, first onset of headache ≥50 years of age, neurological symptoms or signs, trauma, fever, seizures, history of malignancy, history of HIV or active infections, and prior history of stroke or intracranial bleeding. All national headache societies and the European Headache Alliance invited to review and comment the consensus before the final draft. The consensus recommends brain MRI for the case of migraine with aura that persists on one side or in brainstem aura. Persistent aura without infarction and migrainous infarction require brain MRI, MRA and MRV. Brain MRI with detailed study of the pituitary area and cavernous sinus, is recommended for all TACs. For primary cough headache, exercise headache, headache associated with sexual activity, thunderclap headache and hypnic headache apart from brain MRI additional tests may be required. Because there is little and no good evidence the committee constructed a consensus based on the opinion of experts, and should be treated as imperfect.

[Self-medication of regular headache: a community pharmacy-based survey in Belgium]. / Automédication des céphalées fréquentes: étude dans les officines belges.

AIM: This observational community pharmacy-based study aimed to investigate headache characteristics and medication use of persons with regular headache presenting for self-medication. METHODS: Participants (n=1205) completed ii) a questionnaire to assess current headache medication and previous physician diagnosis, (ii) the ID Migraine Screener [ID-M] and (iii) the MIDAS questionnaire. RESULTS: Forty-four % of the study population (n=528) did not have a physician diagnosis of their headache, and 225 of them (225/528, 42.6%) were found to be ID-M positive. The most commonly used acute headache drugs were paracetamol (used by 62% of the study population), NSAIDs (39%) and combination analgesics (36%). Only 12% of patients physician-diagnosed with migraine used prophylactic migraine medication, and 25% used triptans. About 24% of our sample (n=292) chronically overused acute medication, which was combination analgesic overuse (n=166), simple analgesic overuse (n=130), triptan overuse (n=19), ergot overuse (n=6) and opioid overuse (n=51). Only 14.5% was ever advised to limit intake frequency of acute headache treatments. CONCLUSIONS: This study identified underdiagnosis of migraine, low use of migraine prophylaxis and triptans, and high prevalence of medication overuse among subjects seeking self-medication for regular headache. Community pharmacists have a strategic position in education and referral of these self-medicating headache patients.

Cyclic vomiting syndrome: case report and short review of the literature.

Cyclic vomiting syndrome (CVS) is a functional disorder that is considered to be a manifestation of migraine diathesis. It is characterized by stereotypical episodes of severe nausea and vomiting lasting several hours or days, with return to baseline health between episodes. CVS is still an insufficiently known syndrome among physicians, and is therefore often misdiagnosed. Treatment focuses on the different phases of CVS, with interepisodic prophylaxis, abortive therapy in the prodromal phase of CVS, and supportive care during an acute vomiting episode. Anti-migraine medications have been effectively used for prophylaxis in many patients. We report a case of CVS successfully treated with flunarizine, a non-selective calcium antagonist.

Self-medication of regular headache: a community pharmacy-based survey.

BACKGROUND: This observational community pharmacy-based study aimed to investigate headache characteristics and medication use of persons with regular headache presenting for self-medication. METHODS: Participants (n = 1205) completed (i) a questionnaire to assess current headache medication and previous physician diagnosis, (ii) the ID Migraine Screener (ID-M), and (iii) the Migraine Disability Assessment questionnaire. RESULTS: Forty-four percentage of the study population (n = 528) did not have a physician diagnosis of their headache, and 225 of them (225/528, 42.6%) were found to be ID-M positive. The most commonly used acute headache drugs were paracetamol (used by 62% of the study population), NSAIDs (39%), and combination analgesics (36%). Only 12% of patients physician-diagnosed with migraine used prophylactic migraine medication, and 25% used triptans. About 24% of our sample (n = 292) chronically overused acute medication, which was combination analgesic overuse (n = 166), simple analgesic overuse (n = 130), triptan overuse (n = 19), ergot overuse (n = 6), and opioid overuse (n = 5). Only 14.5% was ever advised to limit intake frequency of acute headache treatments. CONCLUSIONS: This study identified underdiagnosis of migraine, low use of migraine prophylaxis and triptans, and high prevalence of medication overuse amongst subjects seeking self-medication for regular headache. Community pharmacists have a strategic position in education and referral of these self-medicating headache patients.

Saccade behaviour in migraine patients.

BACKGROUND: Voxel-based morphometry studies in migraine patients showed significant grey matter volume reduction in regions involved in the control of saccadic eye movements. We hypothesized that these changes would be reflected in dysfunctional saccadic behaviour. METHODS: Saccades were recorded by infrared oculography using three different paradigms (pro-saccade with gap, pro-saccade overlap and anti-saccade with gap). We compared the results for migraine patients (n = 80) with those for controls (n = 87). RESULTS: No significant differences were found between migraine patients with (n = 46) and without (n = 34) aura. Migraine patients showed a saccadic behaviour that differed from controls in three respects. In migraine patients, the latencies in the pro-saccade with gap paradigm were borderline significantly longer. Moreover, in both the pro-saccade with gap and the pro-saccade overlap paradigm we observed a larger intra-individual variation of the latency in migraine patients. However, the biggest difference was that the patients who received migraine prophylactic therapy made significantly more anti-saccade errors in the anti-saccade with gap paradigm, suggesting that inhibitory saccade control is impaired in migraine patients depending on the severity of the migraine. CONCLUSION: We suggest a deficient inhibitory control, reflecting an executive dysfunction in the dorsolateral prefrontal cortex or a dysfunction in the cingulate cortex, is present in migraine patients.

Phenotype of patients responsive to occipital nerve stimulation for refractory head pain.

Occipital nerve stimulation (ONS) has been employed off-label for medically refractory head pain. Identification of specific headache diagnoses responding to this modality of treatment is required. Forty-four patients with medically refractory head pain and treated with ONS were invited to participate in a retrospective study including a clinical interview and, if necessary, an indomethacin test to establish the headache phenotype according to the International Classification of Headache Disorders, 2nd edn (ICHD-II). We gathered data from questionnaires before implantation, at 1 month after implantation, and at long-term follow-up. Twenty-six patients consented and were phenotyped. At 1 month follow-up and at long-term follow-up a significant decrease in all pain parameters was noted, as well as in analgesic use. Quality of sleep and quality of life improved. Patient satisfaction was generally high as 80% of patients had ≥ 50% pain relief at long-term follow-up. The overall complication rate was low, but revisions were frequent. After phenotyping, two main groups emerged: eight patients had 'Migraine without aura' (ICHD-II 1.1) and eight patients 'Constant pain caused by compression, irritation or distortion of cranial nerves or upper cervical roots by structural lesions' (ICHD-II 13.12). Overuse of symptomatic acute headache treatments was associated with less favourable long-term outcome in migraine patients. We conclude that careful clinical phenotyping may help in defining subgroups of patients with medically refractory headache that are more likely to respond to ONS. The data suggest medication overuse should be managed appropriately when considering ONS in migraine. A controlled prospective study for ONS in ICHD-II 13.12 is warranted.

Diagnostic and therapeutic trajectory of cluster headache patients in Flanders.

OBJECTIVE: A fraction of cluster headache (CH) patients face diagnostic delay, misdiagnosis, undertreatment and mismanagement. Specific data for Flanders are warranted. METHODS: Data on CH characteristics, diagnostic process and treatment history were gathered using a self-administered questionnaire with 90 items in CH patients that presented to 4 neurology outpatient clinics. RESULTS: Data for 85 patients (77 men) with a mean age of 44 years (range 23-69) were analysed. 79% suffered from episodic CH and 21% from chronic CH. A mean diagnostic delay of 44 months was reported. 31% of patients had to wait more than 4 years for the CH diagnosis. 52% of patients consulted at least 3 physicians prior to CH diagnosis. Most common misdiagnoses were migraine (45%), sinusitis (23%), tooth/jaw problems (23%), tension-type headache (16%) and trigeminal neuralgia (16%). A significant percentage of patients had never received access to injectable sumatriptan (26%) or oxygen (31%). Most prescribed preventative drugs after the CH diagnosis were verapamil (82%), lithium (35%), methysergide (31%) and topiramate (22%). Despite the CH diagnosis, ineffective preventatives were still used in some, including propranolol (12%), amitriptyline (9%) and carbamazepine (12%). 31% of patients had undergone invasive therapy prior to CH diagnosis, including dental procedures (21%) and sinus surgery (10%). CONCLUSION: Despite the obvious methodological limitations of this study, the need for better medical education on CH is evident to optimize CH management in Flanders.

Unilateral photophobia or phonophobia in migraine compared with trigeminal autonomic cephalalgias.

Our objective was to compare the presence of self-reported unilateral photophobia or phonophobia, or both, during headache attacks comparing patients with trigeminal autonomic cephalalgias (TACs)--including cluster headache, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and paroxysmal hemicrania--or hemicrania continua, and other headache types. We conducted a prospective study in patients attending a referral out-patient clinic over 5 months and those admitted for an intramuscular indomethacin test. Two hundred and six patients were included. In episodic migraine patients, two of 54 (4%) reported unilateral photophobia or phonophobia, or both. In chronic migraine patients, six of 48 (13%) complained of unilateral photophobia or phonophobia, or both, whereas none of the 24 patients with medication-overuse headache reported these unilateral symptoms, although these patients all had clinical symptoms suggesting the diagnosis of migraine. Only three of 22 patients (14%) suffering from new daily persistent headache (NDPH) experienced unilateral photophobia or phonophobia. In chronic cluster headache 10 of 21 patients (48%) had unilateral photophobia or phonophobia, or both, and this symptom appeared in four of five patients (80%) with episodic cluster headache. Unilateral photophobia or phonophobia, or both, were reported by six of 11 patients (55%) with hemicrania continua, five of nine (56%) with SUNCT, and four of six (67%) with chronic paroxysmal hemicrania. Unilateral phonophobia or photophobia, or both, are more frequent in TACs and hemicrania continua than in migraine and NDPH. The presence of these unilateral symptoms may be clinically useful in the differential diagnosis of primary headaches.

Medication-overuse headache in patients with cluster headache.

OBJECTIVE: Medication-overuse headache (MOH) in cluster headache (CH) patients is incompletely described, perhaps because of the relatively low prevalence of CH. METHODS: The authors describe a retrospective series of 17 patients (13 men, 4 women) with CH who developed MOH in association with overuse of a wide range of monotherapies or varying combinations of simple analgesics (n = 9), caffeine (n = 1), opioids (n = 10), ergotamine (n = 3), and triptans (n = 14). The series includes both episodic (n = 7) and chronic (n = 10) CH patients. RESULTS: A specific triptan-overuse headache diagnosis was made in 3 patients, an opioid-overuse headache diagnosis was made in 1 patient, and an ergotamine-overuse headache diagnosis was made in 1 patient. In approximately half of the patients (n = 8), the MOH phenotype was a bilateral, dull, and featureless daily headache. In the other 9 patients, the MOH was characterized by at least one associated feature, most commonly nausea (n = 6), exacerbation with head movement (n = 5), or throbbing character of the pain (n = 5). The common denominator in 15 patients was a personal or family history, or both, of migraine. The 2 other patients gave a family history of unspecified headaches. Medication withdrawal was attempted and successful in 13 patients. CONCLUSIONS: Medication-overuse headache is a previously underrecognized and treatable problem associated with cluster headache (CH). CH patients should be carefully monitored, especially those with a personal or family history of migraine.

Cerebral blood flow and oxygen metabolism in symptomatic internal carotid artery occlusion by (traumatic) cervical artery dissection.

The present study investigates whether cerebral infarction resulting from internal carotid artery occlusion by cervical dissection is due to emboli, released from a superimposed luminal thrombus, or is due to haemodynamic failure and hypoperfusion. Ten patients with a history of stroke and with a visible cerebral infarct on computed tomographic scan, due to cervical dissection and thrombosis of the internal carotid artery, were studied with positron emission tomography in order to assess the regional cerebral blood flow (rCBF), the regional cerebral metabolic rate of oxygen (rCMRO2) and the regional oxygen extraction fraction (rOEF) in different regions of the brain. rCBF and rCMRO2 were only decreased in the infarct area but not in the peri-infarct zone or elsewhere in the brain. As rOEF was not increased in the affected cerebral hemisphere, the present study suggests artery-to-artery embolism rather than a haemodynamic event as the cause of the stroke. Use of anticoagulants thus appears to be the appropriate treatment in the acute stage.

Cerebral bloodflow and oxygen metabolism in borderzone and territorial infarcts due to symptomatic carotid artery occlusion.

It remains controversial whether borderzone infarcts are due to compromised cerebral perfusion and whether territorial infarcts are caused by artery-to-artery emboli in case of occlusion of the internal carotid artery. The present positron emission tomography study compares with normal controls, the average regional cerebral bloodflow (rCBF), regional oxygen extraction fraction (rOEF) and regional cerebral metabolic rate for oxygen (rCMRO(2)) in the infarct area, the peri-infarct zone, the remaining homolateral hemisphere and in the contralateral hemisphere of 10 patients with borderzone and 17 patients with territorial infarcts, due to internal carotid artery occlusion by atherosclerosis and by cervical dissection. The steady-state technique with oxygen-15 was used. A nearly significant increase of rOEF with lowered rCBF and rCMRO(2) was observed in the peri-infarct zone of patients with territorial infarcts. In patients with borderzone infarcts rCMRO(2) was decreased in the peri-infarct zone, in the remaining homolateral hemisphere and in the contralateral hemisphere without changes in rCBF and rOEF. The present study finds no arguments that impaired cerebral perfusion is a more frequent cause of borderzone than of territorial infarcts.

The prognostic significance of changes in lesion size of established cerebral infarcts on computed tomography of the brain.

BACKGROUND: As a second part of our prospective study, we assessed the size of the infarct lesion on computed tomography (CT) of the brain at two fixed time points after stroke in order to investigate its influence on the clinical outcome. METHODS: From 220 consecutive stroke patients, admitted within 24 h after onset with symptoms lasting more than 24 h, we selected 150 displaying an anterior circulation infarct or syndrome. All included patients had CT scans without contrast enhancement on day 3 (+/- 8 h) and on day 10 (+/- 8 h) after stroke onset. The size of the X-ray hypoattenuation zone was determined by superimposing the CT slices on digital cerebral vascular maps, on which the contours of the infarct area were delineated. The lesion size was expressed as the fraction of the total surface area of these digital cerebral maps. The patients were divided into four groups according to their degree of disability at 3 months on the modified Rankin (R) scale as follows : R 0-1, R 2-3, R 4-5, R 6. RESULTS: There was a clear association between lesion size on CT, on day 3 and on day 10, and the clinical outcome. Lesion size decreased between day 3 and day 10 in the groups R 0-1 and R 2-3, remained unchanged in the group R 4-5 and further increased in group R 6. CONCLUSION: Lesion size on CT is a significant predictor of stroke outcome. It decreases from day 3 to day 10 in patients with no or low disability at 3 months, but increases in those who do not survive their stroke.