Treatment of intractable chronic cluster headache by occipital nerve stimulation: a cohort of 51 patients.

BACKGROUND AND PURPOSE: Chronic cluster headache is a rare, highly disabling primary headache condition. When medically intractable, occipital nerve stimulation can offer effective treatment. Open-label series have provided data on small cohorts only. METHODS: We analyzed 51 subjects to evaluate the long-term outcomes of highly intractable chronic cluster headache with occipital nerve stimulation. Patients with intractable chronic cluster headache were implanted with occipital nerve stimulators during the period 2007-2014. The primary endpoint was improvement in daily attack frequency. Secondary endpoints included attack severity, attack duration, quality-of-life measures, headache disability scores and adverse events. RESULTS: We studied 51 patients [35 males; mean age at implant 47.78 (range 31-70) years; mean follow-up 39.17 (range 2-81) months]. Nineteen patients had other chronic headache types in addition in chronic cluster headache. At final follow-up, there was a 46.1% improvement in attack frequency (P < 0001) across all patients, 49.5% (P < 0.001) in those with cluster headache alone and 40.3% (P = 0.036) in those with multiple phenotypes. There were no significant differences in response in those with or without multiple headache types. The overall response rate (defined as at least a 50% improvement in attack frequency) was 52.9%. Significant reductions were also seen in attack duration and severity. Improvements were noted in headache disability scores and quality-of-life measures. Triptan use of responders dropped by 62.56%, resulting in significant cost savings. Adverse event rates were highly favorable. CONCLUSION: Occipital nerve stimulation appears to be a safe and efficacious treatment for highly intractable chronic cluster headache even after a mean follow-up of over 3 years.

Greater occipital nerve blocks in chronic cluster headache: a prospective open-label study.

BACKGROUND AND PURPOSE: Greater occipital nerve blockade (GONB) has been shown to be effective in episodic cluster headache. However, its use in chronic cluster headache (CCH) is less certain. The study aims to prospectively assess the efficacy and consistency of response to GONB in a large series of CCH patients. METHODS: CCH patients who had a unilateral GONB and were referred to the National Hospital for Neurology and Neurosurgery were studied prospectively. Headache characteristics were collected using headache diaries. Responders were considered to be patients with a complete or partial response lasting at least 7 days. In a subgroup of responders the outcomes of serial GONB performed at 3-monthly intervals were also analysed. RESULTS: Eighty-three CCH patients were studied. After the first GONB, a positive response was observed in 47 (57%) patients: 35 (42%) were rendered pain free, 12 (15%) had a partial benefit and one patient obtained <50% improvement. The duration of a positive response lasted a median of 21 days (range 7-504 days). There was a transient worsening of condition in 6% of patients. The overall rate and average duration of response remained consistent after the second [n = 37; 31 responders (84%); median duration 21 days], third [n = 28; 20 responders (71%); median duration 25 days] and fourth [n = 14; 10 responders (71%); median duration 23 days] injections. CONCLUSION: GONB seems to be an efficacious treatment with reproducible effects in CCH patients. Performed three monthly, GONB may have a useful role in the management of CCH.

The clinical characteristics of headache in patients with pituitary tumours.

The clinical characteristics of 84 patients with pituitary tumour who had troublesome headache were investigated. The patients presented with chronic (46%) and episodic (30%) migraine, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT; 5%), cluster headache (4%), hemicrania continua (1%) and primary stabbing headache (27%). It was not possible to classify the headache according to International Headache Society diagnostic criteria in six cases (7%). Cavernous sinus invasion was present in the minority of presentations (21%), but was present in two of three patients with cluster headache. SUNCT-like headache was only seen in patients with acromegaly and prolactinoma. Hypophysectomy improved headache in 49% and exacerbated headache in 15% of cases. Somatostatin analogues improved acromegaly-associated headache in 64% of cases, although rebound headache was described in three patients. Dopamine agonists improved headache in 25% and exacerbated headache in 21% of cases. In certain cases, severe exacerbations in headache were observed with dopamine agonists. Headache appears to be a significant problem in pituitary disease and is associated with a range of headache phenotypes. The presenting phenotype is likely to be governed by a combination of factors, including tumour activity, relationship to the cavernous sinus and patient predisposition to headache. A proposed modification of the current classification of pituitary-associated headache is given.

A PET study exploring the laterality of brainstem activation in migraine using glyceryl trinitrate.

Migraine is a common disabling condition likely to be associated with dysfunction of brain pathways involved in pain and other sensory modalities. A cardinal, indeed signature, feature of the disorder that led to its name is that the pain may be lateralized. H(2)15O-labelled PET was used to study 24 migraineurs and eight healthy controls. The migraineurs were divided into three groups according to the site of their headache: right, left or bilateral. In each group, a migraine was induced using a glyceryl trinitrate (GTN) infusion. The subjects were scanned at predefined points: pre-infusion, during GTN, during migraine and post-migraine. SPM99 software was used to analyse the data. Significant brainstem activation was seen in the dorsal lateral pons (P < 0.05 after small volume correction) during the migraine state versus the pain-free state when comparing migraineurs with controls. When each group was analysed separately, to investigate laterality, it was found that the dorsal pontine activation was ipsilateral in the right-sided and left-sided groups and bilateral in the bilateral headache group with a left-sided preponderance. Consistent with previous work, the activation persisted after pain was controlled by sumatriptan. These results suggest that lateralization of pain in migraine is due to lateralized brain dysfunction.

Post-traumatic chronic paroxysmal hemicrania (CPH) with aura.

The authors describe a patient who developed chronic paroxysmal hemicrania (CPH) in close temporal relationship to a head injury. The subsequent attacks of CPH were associated with a typical migrainous sensory and motor aura. Administration of indomethacin 75 mg daily resulted in isolated occurrence of autonomic and aura symptoms in the absence of pain symptoms. The patient became completely asymptomatic on indomethacin 100 mg daily. Migrainous aura may be seen with trigeminal-autonomic headaches and may represent the expression of an aura-susceptibility gene rather than typical migraine headache biology.

Purinoceptors mediating relaxation and spasm in the rat gastric fundus.

1. The relaxant and spasmogenic effects of purines and analogues were studied in longitudinal strips of rat gastric fundus to characterize the purinoceptors involved. Classification was studied by use of agonist potency orders and of antagonists in circumstances where the influence of confounding factors was reduced. In general tone was raised by carbachol (0.1 microM). 2. Adenosine produced relaxation and was potentiated by nitrobenzylthioinosine (NBTI, 0.3 and 30 microM), an adenosine-uptake inhibitor. 8-Sulphophenyl-theophylline (8-SPT, 30 microM), a selective P1-purinoceptor antagonist, antagonized adenosine and 5'-N-ethylcarboxamidoadenosine (NECA), a selective agonist at P1-purinoceptors. 3. At resting tone, adenosine 5'-triphosphate (ATP) induced a small, phasic relaxation followed by a maintained spasm. When tone was raised by carbachol, ATP induced a larger relaxation followed by a smaller spasm. NBTI did not potentiate ATP, nor did 8-SPT antagonize ATP, suggesting that ATP does not act directly or indirectly at P1-purinoceptors. 4. With raised tone, and in the presence of indomethacin (10 microM) and 8-SPT (30 microM), 2-methylthio ATP (2-MeSATP) and ATP produced relaxations followed by spasms while alpha,beta-methylene ATP (alpha,beta-MeATP) induced only relaxation; all responses were concentration-dependent. The compounds had similar slopes and maxima for relaxation and spasm. The rank orders of potency were 2-MeSATP much greater than alpha,beta-MeATP greater than ATP for relaxation and 2-MeSATP much greater than ATP for spasm.5. With raised tone, and in the presence of indomethacin and alpha 8-SPT, desensitization to alpha,beta-MeATP (100microM) completely and only slightly suppressed responses to ATP and 2-MeSATP, respectively, as relaxants but had no effect on relaxant responses to adenosine. The magnitude of the spasms to ATP and 2-MeSATP was considerably increased by desensitization with alpha,beta-MeATP but the spasm to KCl was not affected.6. With raised tone, and in the presence of indomethacin and 8-SPT, reactive blue 2 (10 AM) nonselectively antagonized ATP, 2-MeATP, a,P-MeATP, adenosine and isoprenaline as relaxants. Reactive blue 2 prevented the spasms to ATP and 2-MeSATP but not spasm to KC1.7. With raised tone, and in the presence of indomethacin, suramin (100 microM) antagonized ATP, but not adenosine, as relaxants and antagonized ATP, but not KC1, as spasmogens.8. It is proposed that adenosine is susceptible to nucleoside-specific uptake and acts predominantly via a P,-purinoceptor and also by a non-PI-purinoceptor mechanism. ATP- and alpha,beta-MeATP-induced relaxations probably occur via a P2x-purinoceptor. The anomalous nature of the 2-MeSATP-induced relaxation suggests it acts both via a P2x-purinoceptor and an additional mechanism. A P2y-purinoceptor is most likely to be involved in the spasms to ATP and 2-MeSATP. Therefore, the functional nature of the responses mediated by P2X- and P2y-purinoceptors, relaxation and spasm respectively, are opposite to those seen in most smooth muscles.

Paroxysmal hemicrania in a family.

Paroxysmal hemicrania (PH) is a trigeminal autonomic cephalgia, characterised by unilateral attacks responsive to indomethacin. There are no published reports of a family history in PH. We report a mother and daughter both with PH. The daughter and her sister also had migraine.

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.

Functional brain imaging in hemicrania continua: implications for nosology and pathophysiology.

Hemicrania continua is a strictly unilateral, continuous headache of mild to moderate intensity, with superimposed exacerbations of moderate to severe intensity that are accompanied by trigeminal autonomic features and migrainous symptoms. The syndrome is exquisitely responsive to indomethacin. Its clinical phenotype overlaps with that of the trigeminal autonomic cephalalgias and migraine, in which the hypothalamus and the brain stem, respectively, have been postulated to play central pathophysiologic roles. A recent positron-emission tomography study of a cohort of patients with hemicrania continua demonstrated significant activation of the contralateral posterior hypothalamus and ipsilateral dorsal rostral pons in association with the headache of hemicrania continua. In addition, there was activation of the ipsilateral ventrolateral midbrain, which extended over the red nucleus and the substantia nigra and bilateral pontomedullary junction. No intracranial vessel dilatation was obvious.

Verapamil induced gingival enlargement in cluster headache.

Verapamil is an effective prophylactic treatment for cluster headaches and, therefore, is widely used. This report describes four patients with cluster headache who developed gingival enlargement after initiating treatment with verapamil. In two patients, it was possible to control this side effect adequately by optimising oral hygiene and dental plaque control. In the other two patients, lowering of the verapamil dose, in addition to optimal oral hygiene and dental plaque control, was necessary; in one patient verapamil had to be stopped completely to reverse the gingival enlargement. Doctors treating cluster headache with verapamil need to be aware of this side effect, especially as it may be preventable with good dental hygiene and dental plaque control, is reversible with reduction or cessation of verapamil, and can lead to dental loss.

Octreotide is not effective in the acute treatment of migraine.

The aim of this study was to determine whether subcutaneous octreotide is effective for the treatment of acute migraine. Patients with migraine with and without aura as classified by the International Headache Society were recruited to a double-blind placebo-controlled crossover study. Patients were instructed to treat two attacks of at least moderate pain severity, with at least a 7 day interval, using subcutaneous 100 microg octreotide or matching placebo. The primary endpoint was the headache response defined as: severe or moderate pain becomes mild or nil, at 2 h. The primary endpoint was analysed using a Multilevel Analysis approach. Secondary end-points included associated symptoms and a four-point functional disability score. The study was powered to detect a 30% difference at an alpha of 0.05 and a beta of 0.8. A total of 51 patients were recruited, of whom 42 provided efficacy data on an attack treated with octreotide and 41 with placebo. Modelling the headache response as a binomial determined by treatment, using the patient as the level 2 variable, and considering a possible period effect, and sex and migraine type as other variables of interest, subcutaneous octreotide was not significantly superior to placebo. The two hour headache response rates were 20% for placebo and 14% for octreotide, whilst the two hour pain free rates were 7% and 2%, respectively. Subcutaneous octreotide 100 microg is not effective in the acute treatment of migraine when compared to placebo.

Students' perception of good and bad teaching: report of a critical incident study.

Evaluation of teaching by the use of questionnaires to students is now commonplace. If it is to be useful the data obtained must be reliable and valid. One criterion of reliability is the response rate, and a low response rate may indicate low validity, i.e. that the questions asked do not reflect the students' real concerns. In order to inform questionnaire design a critical incident study was undertaken. A 20% random sample of students in each of the 5 years of the course were asked to describe one piece of good teaching and one piece of bad teaching, and say why they were good or bad. There was a 65% response rate, and replies were independently categorized by three people. The factors identified fell into three 'domains': interpersonal behaviour of teachers; planning and preparation; and the ability to run the session well. There was no evidence that teaching which 'played to the gallery' or was very examination-oriented would earn high ratings from students.

Benign cough headache.

Benign cough headache is an uncommon primary headache disorder marked by short-lasting attacks of pain triggered by coughing. Magnetic resonance imaging of the brain is required to assure that the cough headache is truly benign. The aetiology of the pain is unclear, but is probably associated with the brief increased intracranial pressure that attends coughing. We have reviewed the clinical features, aetiology, differential diagnosis, management, and prognosis of benign cough headache.

Prolactinomas, dopamine agonists and headache: two case reports.

Headache is a common problem in patients with pituitary tumours. Small pituitary lesions can cause debilitating headache, suggesting that the size of the pituitary tumour may not be the only causal factor in pituitary-related headache. We present two cases of prolactinoma-associated headache. The first case has a clinical diagnosis of short-lasting unilateral headache attacks with conjunctival injection and tearing (SUNCT). The second case has a clinical diagnosis of hemicrania continua and idiopathic stabbing headache. In each case, the administration of dopamine agonists has led to an exacerbation of symptoms. We review the relevant literature to understand the pathophysiological implications of these cases.

The paroxysmal hemicrania-tic syndrome.

Two cases of paroxysmal hemicrania (PH) associated with trigeminal neuralgia are reviewed. The paroxysmal hemicrania component in one patient was episodic, while it was chronic in the other. Each headache type responded completely to separate treatment, highlighting the importance of recognizing this association. We review the six other cases of chronic paroxysmal hemicrania-tic (CPH-tic) reported, and suggest that the term paroxysmal hemicrania-tic syndrome (PH-tic) be used to describe this association.

SUNCT syndrome responsive to intravenous lidocaine.

Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) is a primary headache syndrome that has been reported to be resistant to treatment with intravenous lidocaine. We report four cases of SUNCT in whom intravenous lidocaine (1.3-3.3 mg kg(-1) h(-1)) completely suppressed the headaches for the duration of the infusion. The headache returned after cessation of treatment. Two patients went on to have their symptoms controlled on topiramate (50-300 mg daily). One patient had typical migrainous aura in association with some of the attacks of pain but never migrainous headaches. These cases suggest that treatment with lidocaine can be considered when acute intervention is required to suppress a severe exacerbation of SUNCT, and further broaden the therapeutic and clinical background of this syndrome.

No change in the structure of the brain in migraine: a voxel-based morphometric study.

Migraine is a common, disabling form of primary neurovascular headache. For most of the twentieth century it was regarded as a vascular headache whose primary pathophysiology lay in the cranial vasculature. Functional brain imaging using positron emission tomography has demonstrated activation of the rostral brain stem in acute migraine. Voxel-based morphometry is a new fully automated whole brain technique that is sensitive to subtle macroscopic and mesoscopic structural differences between groups of subjects. In this study 11 patients suffering from migraine with aura (10 females, one male: 23-52 years, mean 31); 11 controls (10 females, one male: 23-52, mean 31); 17 patients with migraine without aura (16 females, one male: 24-57, mean 34); 17 controls (16 females, one male: 24-57, mean 34) were imaged with high resolution volumetric magnetic resonance imaging. There was no significant difference in global grey or white matter volumes between either patients with migraine and controls, or patients with aura and without aura. This study did not show any global or regional macroscopic structural difference between patients with migraine and controls, with migraine sufferers taken as homogenous groups. If structural changes are to be found, other methods of phenotyping migraine, such as by genotype or perhaps treatment response, may be required to resolve completely whether there is some subtle structural change in the brain of patients with migraine.

SUNCT syndrome secondary to prolactinoma.

Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) syndrome is a rare form of primary headache disorder, although secondary causes, particularly posterior fossa abnormalities, are well known. We report a case of SUNCT syndrome secondary to a prolactinoma. Administration of dopamine agonists led to complete resolution of the SUNCT attacks. This case, together with other similar case reports in the literature, highlight the importance of excluding a diagnosis of pituitary adenoma in all suspected cases of SUNCT syndrome, especially as the headache can precede more classical pituitary symptoms by a considerable period of time. Clinicians managing patients with suspected SUNCT syndrome should elicit a history of symptoms associated with pituitary neoplasms, perform a magnetic resonance imaging scan of the brain and pituitary, and screen for serum hormonal abnormalities.