A report of cranial autonomic symptoms in migraineurs

The presence of cranial autonomic symptoms in migraine is well known and thought to represent activation of the trigeminal parasympathetic reflex pathway similar to trigeminal autonomic cephalalgias. However, studies regarding the prevalence of these symptoms are few. The characteristics of migraineurs with cranial autonomic symptoms and the association of cranial autonomic symptoms with laterality of headache have never been studied in a clinic population. Seventy-eight consecutive subjects with migraine were recruited from the Headache Clinic of the Department of Psychiatry after exclusion of subjects with secondary headache. Their demographic data and detailed history of headache were noted and leading questions were asked regarding cranial autonomic symptoms. chi(2) test and Fisher's exact test was used for categorical variables, whereas an independent sample t-test was applied on numerical data. Spearman's correlation was used for correlational analysis of categorical variables. Female subjects (78.2%) outnumbered males and the average duration of illness in the whole sample was 3.81 years. Migraine without aura (53.8%) was the commonest diagnosis, followed by migraine with aura (24.4%). Cranial autonomic symptoms were present in 73.1% of subjects and, commonly, they were ipsilateral to headache. Moreover, strictly unilateral cranial autonomic symptoms were reported by only 32% of patients. The anatomical side of headache did not affect the presence of autonomic symptoms. Those with or without autonomic symptoms did not differ with respect to gender, diagnosis, laterality of headache or associated symptoms except phonophobia, which was more common in subjects with autonomic symptoms (P = 0.05). Those with autonomic symptoms had longer duration of illness (P = 0.03) and longer headache episodes (P = 0.04). In addition, sleep was ineffective in relieving their headache (P = 0.02). Cranial autonomic symptoms are frequent in migraineurs and are common in subjects with long duration of illness and longer headache episodes. Clinical evidence in the present study suggests that subjects with cranial autonomic symptoms have a hyperactive efferent arm of trigeminal autonomic reflex. The connections of trigeminal nucleus with the locus coeruleus and dorsal raphe nucleus may account for the observed phenotypic differences between the two groups. Further research, however, is required to elucidate the underlying neural mechanisms of cranial autonomic symptoms in migraine.     

Rizatriptan in migraineurs with unilateral cranial autonomic symptoms: a double-blind trial

The objective and background is to confirm in a double-blind, placebo-controlled study the high triptan response rates we had previously reported in an open study in migraine patients with unilateral cranial autonomic symptoms. In this randomized, double-blind, placebo-controlled study 80 migraineurs with unilateral cranial autonomic symptoms were assigned to receive rizatriptan 10 mg wafer or placebo (ratio 1:1) and treated for a single moderate or severe migraine attack. The primary endpoints were pain freedom at 2 h and total migraine freedom at 2 h. Secondary endpoints included pain relief, no associated symptoms and sustained pain freedom or relief. Significantly more patients reported pain freedom at 2 h after taking rizatriptan (54 %) than after placebo (8 %) (therapeutic gain 46 % [28 %; 64 %]; P < 0.001). Similarly, significantly more patients reported total migraine freedom at 2 h after rizatriptan (51 %) than after placebo (8 %) (therapeutic gain 43 % [26 %; 61 %]; P < 0.001). Rizatriptan was also more effective than placebo on most secondary endpoints. We confirm in a placebo-controlled study our previous data suggesting that the presence of unilateral cranial autonomic symptoms in migraineurs predicts a positive response to triptans, probably owing to intense trigeminal peripheral afferent activation which strongly recruits peripheral neurovascular 5-HT1B/1D receptors. Acute and preventive pharmacological trials in migraine should focus also on this subset of migraine patients.     

Sumatriptan in migraine with unilateral cranial autonomic symptoms: an open study

OBJECTIVE: To investigate the response to sumatriptan in migraineurs with unilateral cranial autonomic symptoms such as lacrimation, eye redness, eyelid edema, nasal congestion, and rhinorrhea. BACKGROUND: Given the potential large-scale recruitment of peripheral neurovascular 5-HT1B/1D receptors consequent to the activation of the trigeminal autonomic reflex in such patients, the presence of unilateral cranial autonomic symptoms may predict a positive response to sumatriptan. METHODS: Seventy-two consecutive migraineurs with unilateral cranial autonomic symptoms were given sumatriptan 50-mg tablets to treat 1 migraine attack and were asked to record their clinical response to the drug at different time points. End points were pain-relief and pain-free response at 1 and 2 hours. RESULTS: Pain relief was reported by 47 patients (65.3%) at 1 hour and by 59 (81.9%) at 2 hours. Pain-free response was reported by 22 patients (30.6%) at 1 hour and by 44 (61.1%) at 2 hours. Responsiveness to sumatriptan did not correlate with the type or number of unilateral cranial autonomic symptoms, demographic characteristics, prophylactic treatments, use of contraceptives, or concomitant tension-type headache. CONCLUSIONS: Migraineurs with unilateral cranial autonomic symptoms seem to respond to sumatriptan better than other migraineurs. The presence of unilateral cranial autonomic symptoms may predict a positive response to the triptans.     

A History of Cigarette Smoking Is Associated With the Development of Cranial Autonomic Symptoms With Migraine Headaches

(Headache 2011;51:85‐91) Objective.— To look at the smoking history of migraine patients and to determine if a history of cigarette smoking is associated with the development of cranial autonomic symptoms with migraine headaches. Background.— It has recently been noted that a significant number of migraine patients may develop autonomic symptoms during their attacks of headache. Why some headache patients activate the trigeminal autonomic reflex and develop cranial autonomic symptoms while others do not is unknown. Cluster headache occurs more often in patients with a history of cigarette smoking, suggesting a link between tobacco exposure and cluster headache pathogenesis. Could cigarette smoking in some manner lead to activation of the trigeminal‐autonomic reflex in headache patients? If cigarette smoking does lower the threshold for activation of the trigeminal autonomic reflex then do migraine patients who have a history of cigarette smoking more often develop cranial autonomic symptoms than migraineurs who have never smoked? Methods.— Consecutive patients diagnosed with migraine (episodic or chronic) who were seen over a 7‐month time period at a newly established headache center were asked about the presence of cranial autonomic symptoms during an attack of head pain. Patients were deemed to have positive autonomic symptoms along with headache if they experienced at least one of the following symptoms: eyelid ptosis or droop, eyelid or orbital swelling, conjunctival injection, lacrimation, or nasal congestion/rhinorrhea. A smoking history was determined for each patient including was the patient a current smoker, past smoker, or had never smoked. Patients were deemed to have a positive history of cigarette smoking if they had smoked continuously during their lifetime for at least at 1 year. Results.— A total of 117 migraine patients were included in the analysis (96 female, 21 male). Forty‐six patients had a positive smoking history, while 71 patients had no smoking history. Some 70% (32/46) of migraineurs with a positive history of cigarette smoking had cranial autonomic symptoms along with their headaches, while only 42% (30/71) of the nonsmoking patients experienced at least 1 autonomic symptom along with headaches and this was a statistically significant difference (P < .005). In total, 74% of current smokers had autonomic symptoms with their headaches compared with 61% of past smokers and this was not a statistically significant difference. There was a statistically significant difference between the number of current smokers who had autonomic symptoms with their headaches compared with the number of patients who never smoked and had autonomic symptoms (P < .05). Overall, 52% of the studied migraineurs had autonomic symptoms. There was a statistically significant difference between autonomic symptom occurrence in male and female smokers vs male and female nonsmokers. Each subtype of cranial autonomic symptoms was all more frequent in smokers. Conclusion.— A history of cigarette smoking appears to be associated with the development of cranial autonomic symptoms with migraine headaches.     

Unilateral cranial autonomic symptoms in migraine

Unilateral cranial autonomic symptoms (UAs) such as lacrimation, conjunctival injection, eyelid oedema and nasal congestion, which are the hallmark of trigeminal autonomic cephalgias, may also occur in an as yet undetermined proportion of migraine patients. We studied 177 consecutive migraineurs to assess the frequency of UAs and the clinical characteristics of such patients. UAs were reported by 81 patients (45.8%), ocular symptoms alone or in combination with nasal symptoms being the most frequent. The headache was more severe (P<0.0002) and more strictly unilateral (P<0.0004) in patients who reported UAs than in those without. Thus, the presence of UAs suggests an activation of the trigeminal-autonomic reflex, probably related to an over-activation of the trigeminal afferent arm. These findings could have therapeutic implications, given the potential large-scale recruitment of peripheral neurovascular 5-HT(1B/1D) receptors (the target of acute migraine treatment) in such patients.     

Diagnosis and Clinical Features of Trigemino‐Autonomic Headaches

Although severe short‐lasting headaches are rare, they can be considered disabling conditions with a major impact on the quality of life of patients. These headaches can divided broadly in to those associated with autonomic symptoms, so called trigeminal autonomic cephalgias (TACs), and those with few or no autonomic symptoms. The TACs include cluster headache, paroxysmal hemicranias, hemicrania continua, and short‐lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms as well as short‐lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing syndrome. In all of these syndromes, half‐sided head pain and ipsilateral cranial autonomic symptoms such as lacrimation or rhinorrhea are prominent. The paroxysmal hemicranias have, unlike cluster headaches, a very robust response to indomethacin, leading to a notion of indomethacin‐sensitive headaches. The diagnosis of TACs is exclusively a clinical task. Because of the fact that cluster headache is strictly half‐sided, typically involves the region around the eye and temple and often starts in the upper jaw, most patients first consult a dentist or ophthalmologist. No single instrumental examination has yet been able to define, or ensure, the correct diagnosis, or differentiate idiopathic headache syndromes. It is crucial that a trained neurologist sees these patients early so that management can be optimized and unnecessary procedures can be avoided. Although TACS are, in comparison to migraine, quite rare, they are nevertheless clinically very important for the neurologist to consider as they are easy to diagnose and the treatment is very effective in most patients.     

Pharmacological Trials in Migraine: It's Time to Reappraise Where the Headache Is and What the Pain Is Like

Most pharmacological trials deal with migraine as if it were a clinically homogeneous disease, and when detailing its characteristics, they usually report only the presence, or absence, of aura and attack frequency but provide no information on pain location, a non‐trivial clinical detail. The past decade has witnessed growing emerging evidence suggesting that individuals with unilateral pain, especially those with associated unilateral cranial autonomic symptoms, are more responsive than others to trigeminal‐targeted symptomatic and preventive therapy with drugs such as triptans or botulinum toxin. A simple way for migraine research treatment to take a step forward might be to step back, reappraise, and critically evaluate easily obtainable patient‐reported clinical findings along with current knowledge on pain features.     

Migraine Symptoms: Results of a Survey of Self-Reported Migraineurs

Migraine is an episodic headache disorder associated with various combinations of neurologic, gastrointestinal, and autonomic symptoms. Gastrointestinal disturbances including nausea, vomiting, abdominal cramps, or diarrhea are almost universal. Sensory hyperexcitability manifested by photophobia, phonophobia, and osmophobia are frequently experienced. Other symptoms include blurry vision, nasal stuffiness, tenesmus, polyuria, pallor, and sweating, Our telephone interview survey of 500 self-reported migraine sufferers was performed in 1994. The most common reported symptoms associated with migraine were pain, nausea, problems with vision, and vomiting. Nausea occurred in more than 90% of all migraineurs; nearly one third of these experienced nausea during every attack. Vomiting occurred in almost 70% of all migraineurs; nearly one third of these vomited in the majority of attacks. In those who experienced nausea, 30.5% indicated that it interfered with their ability to take their oral migraine medication; in those with vomiting, 42.2% indicated that it interfered with their ability to take their oral migraine medication. The most important features of a migraine medication were rapid and effective relief of headache pain, decreasing the likelihood of headache recurrence, and not causing nausea. Many migraine patients suffer needlessly because their nausea and vomiting are both unreported to, and unrecognized by physicians. The presence of these symptoms is crucial to diagnose migraine not accompanied by aura.     

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.     

Short-lasting unilateral neuralgiform headache with autonomic symptoms syndrome as the initial manifestation of idiopathic hypertrophic cranial pachymeningitis

This is the first report of 2 patients presenting with short-lasting unilateral neuralgiform headache with autonomic symptoms as the initial manifestation of idiopathic hypertrophic cranial pachymeningitis. They both had acute retro-orbital pain ipsilateral to the dural thickening on magnetic resonance imaging of brain, and one had transient miosis as an additional parasympathetic feature. Short-lasting unilateral neuralgiform headache with autonomic symptoms syndrome may be associated with secondary central nervous system pathology, and neuroimaging should be considered in all patients with trigeminal autonomic cephalalgia.     

A population-based analysis of the diagnostic criteria of the International Headache Society

In 740 representative normal subjects a diagnostic headache interview and a neurological examination provided the necessary information to classify headache disorders according to the operational diagnostic criteria of the International Headache Society (IHS). Sixteen per cent (n = 119) had migraine, 78% (n = 578) tension-type headache. In migraineurs, pain was of a pulsating quality in 78%, severe in 85%, unilateral in 62%, and aggravated by routine physical activity in 96%. Tension-type headache was of a pressing quality in 78%, mild or moderate in 99%, bilateral in 90%, and 72% had no aggravation by physical activity. The accompanying symptoms of nausea, photo- and phonophobia occurred frequently and were usually moderate or severe in migraine subjects, and if present in subjects with tension-type headache, they were usually mild. Only two subjects had unclassifiable headache. The IHS Classification is thus exhaustive. The criteria may be improved by mandatory demands to the criterion of pain intensity leaving other features of pain as supportive for the diagnosis and by including graded severity of accompanying symptoms. A specific proposal is given.     

Relationships among migrainous, vascular and orthostatic symptoms

A headache symptom questionnaire was filled out by 766 undergraduate university students and 258 reported one or more headaches per month. Headaches characterized by one or more of the main migrainous symptoms (unilateral pain, gastrointestinal disturbance and focal neurological symptoms) were reported to be more severe, pulsatile, of longer duration, and associated with facial pallor and signs of cerebral vascular instability more frequently than headaches accompanied by few or none of the major migrainous symptoms. Additionally, hunger was reported to trigger headaches associated with migrainous symptoms more frequently than non-migrainous headaches. The results are consistent with the proposal that vascular involvement is one of the factors underlying a continuum of headache with migraine as one extreme.     

Coexisting Trigeminal Autonomic Cephalalgias and Hemicrania Continua

The trigeminal autonomic cephalalgias (TACs) and hemicrania continua (HC) share many clinical characteristics including unilateral pain and ipsilateral autonomic features. We report a patient with a history of migraine without aura who developed cluster headache and HC simultaneously. The distinctive clinical features and differential response profiles to various treatments indicates that they are distinct disorders. We then review previous reports of patients with coexisting TACs and HC and discuss the relationship between these families of primary headache disorders.     

Premonitory and resolution symptoms in migraine: a prospective study in 100 unselected patients

The nosology of migraine premonitory (PS) and resolution (RS) symptoms was studied in 100 migraineurs consulting their general physician. They were asked to fill in, for three attacks, a PS and RS questionnaire. 'True' PS/RS were those experienced the day before (or the day after) the headache had started only if they were not present in a questionnaire completed in a pain-free period. True PS and RS were experienced by 84% and 80%, respectively, of subjects for the first attack. The mean and range (per patient) of PS were 6.8 and 0-21 and of RS 4.7 and 0-15. Anxiety, phonophobia, irritability, unhappiness and yawning were the commonest PS, whereas asthenia, tiredness, somnolence and concentration difficulties were the most common RS. Gender, age and Migraine Disability Assessment scores did not influence PS and RS. Both PS and RS were more frequent in migraine with aura subjects. Patients on preventatives showed a decreased frequency of PS and, to a lesser degree, of RS. Severity of headache was associated with a higher frequency of RS. Individual RS and especially PS were quite consistent after three attacks. Almost two-thirds of the symptoms were noticed in at least two out of three attacks, while more than a half of PS and more than a quarter of RS repeated in three out of three attacks. In conclusion, around 80% of unselected migraineurs experience RS and PS. Migraine with aura and severe pain are risk factors for experiencing PS and RS, while preventatives were protective, especially for PS.     

A clinical study of migraine evolution

BACKGROUND: The buildup time of migraine headaches has not been well delineated in publications to date and we are aware of patients whose migraines last well over 72 hours. More concentration on these factors in the assessment of patients might lead to more appropriate therapeutic choices. METHOD: Prospective ascertainment of such data through a questionnaire completed by 253 informed and willing patients with IHS migraine with or without aura consulting Canadian headache specialists. Data were electronically sent to a central computer from each center, tabulated and analyzed using standard statistical parameters. RESULTS: In 253 patients with migraine ascertained using applied IHS criteria, nausea was a feature in over 90% of cases, especially in those with aura. This inhibited the ingestion of oral medications in about a quarter of all subjects. The time to build from no pain to moderate/severe pain was shorter in subjects with auras and was less than 2 hours in 97% of those with and 86% of those without auras. However, we also identified a group of subjects with migraine (over 10% of all) in whom the build time to maximum pain is delayed for over 2 hours. Nausea was experienced by 91.7% of subjects, slightly but significantly later in those without auras. While most headaches in each group lasted from 4 to 72 hours, 24.3% of those with and 20.6% of those without aura expected to experience pain for more than 72 hours, while in untreated cases disability due to pain, nausea, or malaise usually persisted for over 3 days in 24.3% and 16.7% of those with and without aura, respectively. One-fifth of migraineurs may be in pain and/or disabled by accompanying symptoms for over 3 days in a typical migraine attack. Over half of our subjects reported that their medications worked well or excellently. CONCLUSIONS: Attacks of migraine in real-life clinical situations vary somewhat from the IHS criteria in that they are more often associated with nausea that interferes with oral therapy; can persist for over 72 hours; may have slow (>2 hours) buildup to maximum pain in 10% of cases; and may cause disability for over 3 days. Nevertheless, current therapeutic regimens (including prescribed medications) work well for a substantial majority.     

An unusual form of TAC-TAC sine autonomic phenomena

The trigeminal autonomic cephalalgias (TACs) are characterized by the cardinal combination of short-lasting unilateral pain and autonomic phenomena affecting the head, including cluster headache, paroxysmal hemicrania and SUNCT. Infrequently reported have been cases with dissociation of these two cardinal features- usually with autonomic phenomena without pain, rather than the reverse. Herein is described the case of a 56-year-old man presenting with an unusual form of TAC resembling chronic paroxysmal hemicrania but with a lower frequency of occurrence, with temporal features not typical of previously described TACs, and consisting of severe unilateral head pain without any autonomic symptoms or signs, absolutely responsive to indomethacin.     

A Case of Recurrent Facial Pain Associated With a Pourfour du Petit Syndrome: A New Entity?

We report the case of a 38‐year‐old woman with a history of migraine who experienced an association of recurrent unilateral facial pain and Pourfour du Petit syndrome. The episodes occurred for between a few seconds and up to 3 minutes up to 6 times a day mimicking short‐lasting unilateral neuralgiform headaches with cranial autonomic symptoms. No lesional cause was found and the use of topiramate led to a nearly complete disappearance of the episodes. This new entity raises the question of a novel autonomic dysfunction in short‐lasting unilateral neuralgiform headaches with cranial autonomic symptoms or an unexpected presentation of migraine.     

Side-shifting hemicrania continua with aura (migraine with aura with autonomic symptoms responsive to indomethacin?)

Atypical features of hemicrania continua (HC), including both visual aura and side shifting, have been reported previously. However, auras and variable unilaterality have never been reported together in HC. We report two patients with side-shifting HC with aura. These patients' symptoms are unilateral headaches, visual aura, autonomic features, throbbing pain, nausea and photo/phonophobia. One could speculate that the unilaterality and/or the autonomic symptom modules are indomethacin responsive. The patients can also be classified as chronic migraine with aura, with autonomic symptoms, responsive to indomethacin. Neither migraine subtype nor side-shifting HC with aura is included in the current International Headache Society (IHS) classification, so these patients are not classifiable. Side-shifting HC with aura implies the need to revisit the traditional IHS categorization of headaches into unique diagnostic groups. The modular headache theory may be a tool for the understanding of these rare and complex cases.     

Electrocardiographic changes during migraine attacks

OBJECTIVES: To clarify whether electrocardiographic (ECG) changes can be identified during a migraine attack and to determine whether there are ECG differences between periods with and without headache. BACKGROUND: The clinical signs and symptoms of migraine point to involvement of the autonomic nervous system, and especially to disrupted regulation of the circulatory system and autonomic balance. This disruption may be more marked during a migraine attack. During a migraine attack, autonomic imbalance within the heart and its vessels conceivably may result in ECG abnormalities. METHODS: In 30 patients with migraine, the ECG variables of heart rate, abnormalities of rhythm, PR interval, QRS duration, corrected QT interval, T inversion, and ST-segment changes were recorded during migraine attacks and pain-free periods. RESULTS: Of the 30 patients studied during a migraine attack, 9 (30%) had one or more abnormalities of rhythm (including sinus arrhythmia, atrial premature contraction, and ventricular premature contraction), 20% had PR intervals greater than 0.20 seconds, 40% had corrected QT intervals greater than 0.44 seconds, 66% had T inversion, and 40% had ST-segment abnormalities. No patient had arrhythmia, PR intervals greater than 0.20 seconds, or corrected QT intervals greater than 0.44 seconds during a pain-free period. No differences were noted for ST-segment changes, T inversion, and total ECG changes between periods with and without headache, but both PR and corrected QT intervals were significantly longer during migraine attacks than during pain-free periods. CONCLUSIONS: We conclude that ECG abnormalities often are present during a migraine attack, and for most of these, particularly PR and corrected QT interval lengthening, these abnormalities will be absent or less prominent during pain-free intervals.