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1.  The Neuropsychology of Cluster Headache: Cognition, Mood, Disability, and Quality of Life of Patients With Chronic and Episodic Cluster Headache 
Headache  2015;55(2):287-300.
Background
Cluster headache (CH) is commonly regarded as one of the most disabling headache conditions, and referred to as one of the most painful conditions known to humankind. Although there has been some research indicating the severe impact of CH, there is little comprehensive evidence of its impact on quality of life, disability, mood, and cognitive function in both its episodic (ECH) and chronic (CCH) variants.
Methods
This cross-sectional study investigates various aspects of cognitive function including intelligence, executive function, and memory, and mood, disability, and quality of life in 22 patients with ECH and CCH compared with age-matched healthy controls.
Results
The results showed that intelligence and executive functions are intact in patients with CH, but that patients with CH perform significantly worse than healthy controls on tests of working memory and (all P < .05) report greater cognitive failures (P < .05). Around one third of both the ECH and CCH groups achieved “caseness” for depression, while self-reported anxiety was higher in those with CCH than the ECH patients, with 75% of the former compared with 38% of the latter groups achieving “caseness” on the measure of anxiety. Patients with CH reported high levels of disability, which was not significantly different between the 2 groups (P > .05). The patients with CH reported poor quality of life compared with healthy controls; however, this difference was not statistically significant.
Conclusion
Patients with CH show worse working memory, disturbance of mood, and poorer quality of life compared with healthy controls. The differences between patients with ECH and CCH, and the implications of these findings for the management of CH are discussed.
doi:10.1111/head.12486
PMCID: PMC4354253  PMID: 25688646
chronic cluster headache; episodic cluster headache; cognition; mood; disability; quality of life
2.  OnabotulinumtoxinA for Hemicrania Continua: open label experience in 9 patients 
Background
Hemicrania continua is a strictly unilateral, continuous headache, typically mild to moderate in severity, with severe exacerbations commonly accompanied by cranial autonomic features and migrainous symptoms. It is exquisitely responsive to Indomethacin. However, some patients cannot tolerate treatment, often due to gastrointestinal side effects. Therapeutic alternatives are limited and controlled evidence lacking.
Methods
We present our experience of nine patients treated with OnabotulinumtoxinA for hemicrania continua. All patients were injected using the PREEMPT (Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy) protocol for migraine.
Results
Five of nine patients demonstrated a 50% or more reduction in moderate to severe headache days with OnabotulinumtoxinA with a median reduction in moderate to severe headache days of 80%. Patient estimate of response was 80% or more in five subjects. The median and mean duration of response in the five responders was 11 and 12 weeks (range 6–20 weeks). Improvements were also seen in headache-associated disability
Conclusions
OnabotulinumtoxinA adds a potential option to the limited therapeutic alternatives available in hemicrania continua.
doi:10.1186/s10194-015-0502-z
PMCID: PMC4385246  PMID: 25902798
Botulinum toxin-A; Hemicrania continua; Treatment; Indomethacin
3.  Therapeutic effect of intranasal evaporative cooling in patients with migraine: a pilot study 
Background
Cryotherapy is the most common non-pharmacological pain-relieving method. The aim of this pilot study was to ascertain whether intranasal evaporative cooling may be an effective intervention in an acute migraine attack. Studies have previously demonstrated effectiveness of a variety of cryotherapy approaches. Intranasal evaporative cooling due to vascular anatomy, allows the transfer of venous blood from nasal and paranasal mucous membranes to the dura mater, thereby providing an excellent anatomical basis for the cooling processes.
Methods
We conducted a prospective, open-label, observational, pilot study. Twenty-eight patients who satisfied the International Classification of Headache Disorders (ICHD 2) diagnostic criteria for migraine were recruited. A total of 20 treatments were administered in 15 patients. All patients provided pain severity scores and migraine-associated symptoms severity scores (based on a 0–10 visual analogue scale, [VAS]).
Results
Out of the 20 treatments, intranasal evaporative cooling rendered patients’ pain and symptoms free immediately after treatment, in 8 of the treatments (40%), a further 10 treatments (50%) resulted in partial pain relief (headache reduced from severe or moderate to mild) and partial symptoms relief. At 2 hours, 9 treatments (45%) provided full pain and symptoms relief, with a further 9 treatments (45%) resulting in partial pain and symptoms relief. At 24 hours, 10 treatments (50%) resulted in patients reporting pain and symptom freedom and 3 (15%) provided partial pain relief. In summary 13 patients (87%) had benefit from the treatment within 2 hours that was sustained at 24 hours.
Conclusions
Intranasal evaporative cooling gave considerable benefit to patients with migraine, improving headache severity and migraine-associated symptoms. A further randomised, placebo controlled, double blinded, parallel clinical trial is required to further investigate the potential of this application.
Trial registration
Clinicaltrials.gov registered trial, ClinicalTrials.gov Identifier: NCT01898455.
doi:10.1186/1129-2377-16-5
PMCID: PMC4405521  PMID: 25623151
Intranasal cooling; Migraine
4.  Trigeminal Autonomic Cephalalgias: Beyond the Conventional Treatments 
The trigeminal autonomic cephalalgias include cluster headache, paroxysmal hemicrania, short-lasting unilateral neuralgiform headache attacks, and hemicrania continua. While the majority responds to conventional pharmacological treatments, a small but significant proportion of patients are intractable to these treatments. In these cases, alternative choices for these patients include oral and injectable drugs, lesional or resectional surgery, and neurostimulation. The evidence base for conventional treatments is limited, and the evidence for those used beyond convention is more so. At present, the most evidence exists for nerve blocks, deep brain stimulation, occipital nerve stimulation, sphenopalatine ganglion stimulation in chronic cluster headache, and microvascular decompression of the trigeminal nerve in short-lasting unilateral neuralgiform headache attacks.
doi:10.1007/s11916-014-0438-z
PMCID: PMC4119587  PMID: 24974071
Trigeminal autonomic cephalalgias; Neurostimulation; Nerve blocks; Sphenopalatine ganglion stimulation; Occipital nerve stimulation; Deep brain stimulation
5.  SUNA and red ear syndrome: a new association and pathophysiological considerations 
Red ear syndrome (RES) is characterised by attacks of unilateral or bilateral burning ear pain associated with erythema. Primary and secondary forms have been described. Primary RES appears to have a frequent association with primary headaches especially migraine. Here, we describe the case of a woman with short-lasting unilateral neuralgiform attacks with cranial autonomic symptoms (SUNA) and recurrent episodes of ipsilateral red ear triggerable by cutaneous stimulation. Lamotrigine was beneficial for her SUNA but not for the RES. Both these disorders are extremely rare therefore their coexistence in the same individual may suggest similar pathophysiological mechanisms rather than a chance association.
doi:10.1186/1129-2377-14-32
PMCID: PMC3631130  PMID: 23565730
SUNA; SUNCT; Red ear syndrome; Trigeminal autonomic cephalalgias; Cranial autonomic symptoms
6.  The red ear syndrome 
Red Ear Syndrome (RES) is a very rare disorder, with approximately 100 published cases in the medical literature. Red ear (RE) episodes are characterised by unilateral or bilateral attacks of paroxysmal burning sensations and reddening of the external ear. The duration of these episodes ranges from a few seconds to several hours. The attacks occur with a frequency ranging from several a day to a few per year. Episodes can occur spontaneously or be triggered, most frequently by rubbing or touching the ear, heat or cold, chewing, brushing of the hair, neck movements or exertion. Early-onset idiopathic RES seems to be associated with migraine, whereas late-onset idiopathic forms have been reported in association with trigeminal autonomic cephalalgias (TACs). Secondary forms of RES occur with upper cervical spine disorders or temporo-mandibular joint dysfunction. RES is regarded refractory to medical treatments, although some migraine preventative treatments have shown moderate benefit mainly in patients with migraine-related attacks. The pathophysiology of RES is still unclear but several hypotheses involving peripheral or central nervous system mechanisms have been proposed.
doi:10.1186/1129-2377-14-83
PMCID: PMC3850925  PMID: 24093332
Red ear syndrome; Migraine; Trigemino-autonomic reflex; Trigeminal autonomic cephalalgias; Parasympathetic system; Erythromelalgia
7.  Trigeminal autonomic cephalalgias: A review of recent diagnostic, therapeutic and pathophysiological developments 
Annals of Indian Academy of Neurology  2012;15(Suppl 1):S51-S61.
The trigeminal autonomic cephalalgias (TACs) are a group of primary headache disorders that are characterized by strictly unilateral trigeminal distribution pain occurring in association with ipsilateral cranial autonomic symptoms. This group includes cluster headache, paroxysmal hemicrania and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing. These disorders are very painful, often considered to be some of the most painful conditions known to mankind, and consequently are highly disabling. They are distinguished by the frequency of attacks of pain, the length of the attacks and very characteristic responses to medical therapy, such that the diagnosis can usually be made clinically, which is important because it dictates therapy. The management of TACs can be very rewarding for physicians and highly beneficial to patients.
doi:10.4103/0972-2327.100007
PMCID: PMC3444219  PMID: 23024564
Cluster headache; paroxysmal hemicrania; SUNA; SUNCT; trigeminal autonomic cephalalgias
8.  Migraine, cerebrovascular disease and the metabolic syndrome 
Annals of Indian Academy of Neurology  2012;15(Suppl 1):S72-S77.
Evidence is emerging that migraine is not solely a headache disorder. Observations that ischemic stroke could occur in the setting of a migraine attack, and that migraine headaches could be precipitated by cerebral ischemia, initially highlighted a possibly association between migraine and cerebrovascular disease. More recently, large population-based studies that have demonstrated that migraineurs are at increased risk of stroke outside the setting of a migraine attack have prompted the concept that migraine and cerebrovascular disease are comorbid conditions. Explanations for this association are numerous and widely debated, particularly as the comorbid association does not appear to be confined to the cerebral circulation as cardiovascular and peripheral vascular disease also appear to be comorbid with migraine. A growing body of evidence has also suggested that migraineurs are more likely to be obese, hypertensive, hyperlipidemic and have impaired insulin sensitivity, all features of the metabolic syndrome. The comorbid association between migraine and cerebrovascular disease may consequently be explained by migraineurs having the metabolic syndrome and consequently being at increased risk of cerebrovascular disease. This review will summarise the salient evidence suggesting a comorbid association between migraine, cerebrovascular disease and the metabolic syndrome.
doi:10.4103/0972-2327.100015
PMCID: PMC3444221  PMID: 23024568
Comorbidities; metabolic syndrome; migraine; obesity; stroke
9.  Cluster headache 
BMJ Clinical Evidence  2010;2010:1212.
Introduction
The revised International Headache Society (IHS) criteria for cluster headache are: attacks of severe or very severe, strictly unilateral pain, which is orbital, supraorbital, or temporal pain, lasting 15 to 180 minutes and occurring from once every other day to eight times daily.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to abort cluster headache? What are the effects of interventions to prevent cluster headache? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations, such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 23 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: baclofen (oral); botulinum toxin (intramuscular); capsaicin (intranasal); chlorpromazine; civamide (intranasal); clonidine (transdermal); corticosteroids; ergotamine and dihydroergotamine (oral or intranasal); gabapentin (oral); greater occipital nerve injections (betamethasone plus xylocaine); high-dose and high-flow-rate oxygen; hyperbaric oxygen; leuprolide; lidocaine (intranasal); lithium (oral); melatonin; methysergide (oral); octreotide (subcutaneous); pizotifen (oral); sodium valproate (oral); sumatriptan (oral, subcutaneous, and intranasal); topiramate (oral); tricyclic antidepressants (TCAs); verapamil; and zolmitriptan (oral and intranasal).
Key Points
The revised International Headache Society (IHS) criteria for cluster headache are: attacks of severe or very severe, strictly unilateral pain, which is orbital, supraorbital, or temporal pain, lasting 15 to 180 minutes and occurring from once every other day to eight times daily. The attacks are associated with one or more of the following, all of which are ipsilateral: conjunctival injection, lacrimation, nasal congestion, rhinorrhoea, forehead and facial sweating, miosis, ptosis, and eyelid oedema. Most people are restless or agitated during an attack. Cluster headache may be episodic or chronic. Cluster headache is rare, but the exact prevalence remains a matter of debate.
The main focus of intervention is to abort attacks once they have begun and to prevent future attacks.
Sumatriptan, used subcutaneously or intranasally, and zolmitriptan used intranasally reduce the severity and duration of cluster headache attacks once they have begun. Oral zolmitriptan reduces severity of attacks in people with episodic cluster headache, but we don't know how effective it is in people with chronic cluster headache. We don't know whether oral sumatriptan is effective.
There is consensus that high-dose and high-flow-rate oxygen is effective for abortive treatment of episodic or chronic cluster headache. We don't know whether this consensus can be applied to hyperbaric oxygen, as little research has been conducted.
There is also consensus that subcutaneous octreotide is effective for abortive treatment of cluster headache.
We don't know whether intranasal lidocaine is effective for abortive treatment of cluster headache.
There is consensus that both verapamil and lithium prevent cluster headache, but that verapamil is more effective than lithium, and causes fewer adverse effects. There is also consensus that corticosteroids and greater occipital nerve injections (betamethasone plus xylocaine) are effective for preventive treatment.
We don't know whether baclofen, botulinum toxin, capsaicin, chlorpromazine, civamide, clonidine, ergotamine or dihydroergotamine, gabapentin, leuprolide, melatonin, methysergide, pizotifen, sodium valproate, oral sumatriptan, topiramate, or tricyclic antidepressants are effective for prevention of cluster headache. Some of these interventions are not routinely used in clinical practice.
PMCID: PMC2907610  PMID: 21718584
10.  Occipital nerve stimulation in primary headache syndromes 
Chronic daily headache is a major worldwide health problem that affects 3–5% of the population and results in substantial disability. Advances in the management of headache disorders have meant that a substantial proportion of patients can be effectively treated with medical treatments. However, a significant minority of these patients are intractable to conventional medical treatments. Occipital nerve stimulation (ONS) is emerging as a promising treatment for patients with medically intractable, highly disabling chronic headache disorders, including migraine, cluster headache and other less common headache syndromes. Open-label studies have suggested that this treatment modality is effective and recent controlled trial data are also encouraging. The procedure is performed using several technical variations that have been reviewed along with the complications, which are usually minor and tolerable. The mechanism of action is poorly understood, though recent data suggest that ONS could restore the balance within the impaired central pain system through slow neuromodulatory processes in the pain neuromatrix. While the available data are very encouraging, the ultimate confirmation of the utility of a new therapeutic modality should come from controlled trials before widespread use can be advocated; more controlled data are still needed to properly assess the role of ONS in the management of medically intractable headache disorders. Future studies also need to address the variables that are predictors of response, including clinical phenotypes, surgical techniques and stimulation parameters.
doi:10.1177/1756285611420903
PMCID: PMC3251898  PMID: 22276076
Neuromodulation; headache; occipital nerve stimulation; migraine; cluster headache; SUNCT; SUNA; hemicrania continua

Results 1-11 (11)