This section is updated monthly and provides commentary and summaries of interesting headache research.
Multiple cranial nerve blocks of the greater and lesser occipital, supraorbital, supratrochlear and auriculotemporal nerves are widely used in the treatment of primary headaches. In an uncontrolled open-label prospective study, 119 patients with chronic cluster headache, chronic migraine, short lasting unilateral neuralgiform attack disorders, new daily persistent headaches, hemicrania continua and chronic paroxysmal hemicrania were examined. All had failed to respond to greater occipital nerve blocks. Response was defined as a 50% reduction in either daily attack frequency or moderate-to-severe headache days after 2 weeks.
The response rate of the whole cohort was 55.4%: Chronic cluster headache, 69.2%; chronic migraine, 49.0%; short lasting unilateral neuralgiform attack disorders, 56.3%; new daily persistent headache, 10.0%; hemicrania continua, 83.3%; and chronic paroxysmal hemicrania, 25.0%. Time to benefit was between 0.50 and 33.58 hours. Benefit was maintained for up to 4 weeks in over half of responders in all groups except chronic migraine and paroxysmal hemicrania. Only minor adverse events were recorded.
Erenumab (Aimovig) is a human monoclonal antibody against the calcitonin gene-related peptide (CGRP) receptor and has already been shown to be of benefit in patients with episodic and chronic migraine. This double-blind placebo study examined the effects of Erenumab (70mg and 140mg vs placebo) in 274 patients with chronic migraine and medication-overuse headache.
Patients receiving Erenumab 70 or 140 mg had greater reductions than the placebo group at month 3 in monthly migraine days (mean [95% confidence interval] -6.6 [-8.0 to -5.3] and -6.6 [-8.0 to -5.3] vs -3.5 [-4.6 to -2.4]) and acute migraine-specific medication treatment days (-5.4 [-6.5 to -4.4] and -4.9 [-6.0 to -3.8] vs -2.1 [-3.0 to -1.2]). ≥50% reductions in monthly migraine days were achieved in placebo, 70 and 140 mg groups by 18%, 36% (odds ratio [95% confidence interval] 2.67 [1.36-5.22]) and 35% (odds ratio 2.51 [1.28-4.94]) respectively.
Erenumab reduced migraine frequency and acute migraine-specific medication treatment days in patients with chronic migraine and medication overuse, improving disability and quality of life.
Cortical spreading depression (CSD) is a wave of cortical hyperactivity followed by a wave of inhibition that has been implicated in migraine aura. Animal studies suggest that CSD is associated with neuroinflammation. Using PET/MRI this study looked at glial activation in 13 migraineurs and 16 healthy controls. Standardized uptake value ratio (SUVR) was compared between groups.
in frontoinsular cortex, primary/secondary somatosensory cortices, and basal ganglia.SUVR was elevated in migraineurs compared to healthy controls in nociceptive (pain) areas (e.g.
These findings demonstrate that migraine with aura is associated with neuroimmune activation/neuroinflammation, and support a possible link between CSD and glial activation, previously observed in animals.
Migraine is known to run in families. While some clinical studies have indicated that migraine is disproportionally transmitted through the maternal line, this has not been examined in a population-based setting. Using a cross-sectional design, this study looked at 13,731 parents and 8970 offspring.
There was a significant association between maternal migraine and offspring migraine (odds ratio 2.76, 95% confidence interval 2.18-3.51). A weaker association ( p = 0.004 for comparison with maternal migraine) was found between paternal migraine and offspring migraine (odds ratio 1.67, 95% confidence interval 1.33-2.28). For non-migrainous headache, there was a significant association between mothers and offspring (odds ratio 1.25, 95% confidence interval 1.10-1.43), but not between fathers and offspring.
This study looked at the effects of onabotulinumtoxinA (Botox) used for the treatment of chronic migraine (CM) on comorbid symptoms including, depression, anxiety, fatigue and poor sleep quality. The Patient Health Questionnaire (PHQ-9) and Generalised Anxiety Disorder (GAD-7) scales were used to assess the effects of onabotulinumtoxinA on comorbid symptoms of depression and anxiety, respectively. The effects of onabotulinumtoxinA on associated sleep quality and fatigue were assessed using the Pittsburgh Sleep Quality Index and Fatigue Severity Scale, respectively.
OnabotulinumtoxinA treatment was associated with sustained reduction in headache days. Quality of life and anxiety/depression scores also reduced from baseline. By week 108 clinically meaningful improvements were observed in 78% with depression and 81.5% with anxiety. Sleep quality and symptoms of fatigue also improved. No new safety concerns were identified.
In addition to reducing headache frequency, onabotulinumtoxinA treatment for CM was associated with clinically meaningful reduction in symptoms of depression and anxiety, and improved associated symptoms of poor sleep quality and fatigue.
Depression, anxiety, poor sleep and general fatigue are commonly observed in patients with chronic migraine. This study demonstrated that these comorbid symptoms also improve when chronic migraine is treated with onabotulinumtoxinA (Botox).
Galcanezumab (Emgality®) is an injectable monoclonal antibody against CGRP. In this study the effect of galcanezumab treatment was compared to placebo in adult patients with episodic or chronic migraine.
1773 adult patients with episodic migraine (n = 444 for galcanezumab 120 mg; n = 435 for galcanezumab 240 mg; n = 894 for placebo) and 1113 patients with chronic migraine (n = 278 for galcanezumab 120 mg; n = 277 for galcanezumab 240 mg; n = 558 for placebo) were evaluated.
In patients with episodic migraine, ≥50% response was maintained in 41.1% receiving Galcanezumab 120mg and 41.5% receiving galcanezumab 240 mg for ≥3 consecutive months and 19.0% and 20.5%, respectively, for 6 consecutive months. This was significantly greater than placebo at ≥3 and 6 months consecutively (21.4 and 8.0%, respectively, P < 0.001).
In patients with chronic migraine, ≥50% response was maintained for 3 months in 16.8% receiving Galcanezumab 120mg and 14.6% receiving galcanezumab 240 mg. This was significantly greater than placebo (6.3%, P < 0.001).
Treatment with galcanezumab 120 mg or 240 mg was effective in patients with episodic and chronic migraine.
In November 2018 Emgality® (galcanezumab) received European Commission Approval for the Prophylaxis of Migraine in Adults. Although this offers new hope to patients with migraine it remains unclear when Emgality will be available in the UK and at what cost.
Post traumatic headache frequently results in headache. This study examines the characteristics of post traumatic headache in compensation claimants.
In this observational study 116 consecutive medicolegal notes were reviewed. 88 had suffered from head and neck injury, 21 only neck injury and 7 “other injuries”. 94% of head injuries were classified as mild. Patients with neck injuries were equally likely to develop post traumatic headache as those with head and neck injuries. Patients with “other injuries” did not develop headache. 25% of patients with head and neck injury denied developing headache. Post traumatic headache correlated strongly with a background of previous primary headache (p<0.0001). 90% of post traumatic headache displayed the same seminology as migraine or probable migraine. 40% of patients has received no treatment for headache in primary care.
This study suggests that post traumatic headache is essentially “migraine” triggered by neck or head concussion.
In the absence of any significant structural cause, post traumatic headache should be managed as (chronic) migraine, especially if there is a previous background of primary headache.
Practical and clinical utility of non-invasive vagus nerve stimulation (nVNS) for the acute treatment of migraine: a post hoc analysis of the randomized, sham-controlled, double-blind PRESTO trial. J Headache Pain 2018;19:98
The PRESTO study provided evidence that patients with episodic migraine benefit from non-invasive vagus nerve stimulation (gammaCore®). In this study additional data from the PRESTO study was examined. Patients recorded pain intensity for treated migraine attacks on a 4-point scale and whether acute medication was required.
A significantly higher percentage of patients who used gammaCore® at the time of attacks (n = 120) vs sham (n = 123) reported a ≥ 1-point decrease in pain intensity at 30 min (32.2% vs 18.5%, P = 0.020), 60 min (38.8% vs 24.0%, P = 0.017), and 120 min (46.8% vs 26.2%, P = 0.002) after the first attack. The proportion of patients who did not require rescue medication was significantly higher with gammaCore® than with sham for the first attack (59.3% vs 41.9%, P = 0.013) and all attacks (52.3% vs 37.3%, P = 0.008). When initial pain intensity was mild, the percentage of patients with no pain after treatment was significantly higher with gammaCore® than with sham at 60 min (37.0% vs 21.2%, P = 0.025).
This post hoc analysis demonstrated that use with gammaCore® quickly and consistently reduced pain intensity while decreasing rescue medication use.
This study demonstates the clinical benefits provided by gammaCore® use in the treatment of episodic migraine and therefore has the potential to reduce use of acute pharmacologic medications and their associated adverse events.
assessed whether there is a sustained benefit and good safety with repeated onabotulinumtoxinA (Botox) sessions in chronic migraine over more than three years of treatment. 65 patients with chronic migraine were prospectively followed over 3 years of treatment.
56 (86%) of 65 patients continued Botox over three years. Comparisons were made between data collected during the first and last 3 months of the study. By the end of the 3 years there was a reduction in monthly mean headache days (3.4 ± 1.7 vs 7.2 ± 3.8; P < 0.001). Headaches were also noted to be less severe and patients took acute painkillers on less days (2.8 ± 1.3 vs 4.7 ± 3.2; P < 0.001). Botox was safe and well tolerated with low rates of adverse events or drop-outs.
ong-term treatment with Botox proved to be effective, safe and well tolerated over three years.
Background: Cluster headache is the most painful condition known to medical science. Typically headaches are daily and occur in bouts over several weeks or months. In between bouts patients are often headache free. The majority of cluster attacks are less than 60 minutes. In between attacks patients are usually symptom free. In this study the authors investigate what symptoms patients describe before (preictal), during (ictal) and after (postictal) cluster headaches.
Results: In total 500 attacks from 57 patients were described. Preictal symptoms were described in approximately half of patients and included: problems with concentration; restlessness; and changes in mood. A quarter of patients described autonomic symptoms (e.g. lacrimation) 10 minutes before attacks. Postictally approximately a third of patients described fatigue, decreased energy and concentration difficulties, that on average lasted 60 minutes.
Conclusions: Preictal and postictal symptoms are very common in patients with cluster headache.
For patients: Forewarned is forearmed. Knowledge that a cluster headache is about to occur may potentially enable earlier abortive intervention in some patients.
Tassorelli C, Grazzi L, de Tommaso M, Pierangeli G, Martelletti P, Rainero I, Dorlas S, Geppetti P, Ambrosini A, Sarchielli P, Liebler E, Barbanti P, PRESTO Study Group. Noninvasive vagus nerve stimulation as acute therapy for migraine: The randomized PRESTO study. Neurology 2018 June 15 [Epub ahead of Print].
Background: This study evaluated the efficacy, safety and tolerability of noninvasive vagus nerve stimulation (with the gammaCore device) for the acute treatment of migraine. This was a double-blinded, randomized, sham-controlled study.
Results: 248 patients with episodic migraine, with and without aura were evaluated. Subjects were randomized to use either gammaCore or sham within 20-minutes of onset of pain. Subjects who received gammaCore were significantly more likely to pain free compared to sham at 30-minutes (12.7% vs 4.2%; p=0.012) and 60-minutes (21.0% vs 10.0%; p=0.023). At 120-minutes there was no significant difference between gammaCore and sham (30.4% vs 19.7%; p=0.067).
Conclusions: gammaCore is effective, well tolerated and safe for treatment of acute migraine in some patients.
For patients: gammaCore has not yet been approved by NICE and therefore at present is not readily available on the NHS. Hopefully, the PRESTO study and future studies will provide the level of evidence that is required by NICE for approval. More research is required to determine which patients are most likely to benefit from gammaCore.
Karsan N, Palethorpe D, Rattanawong W, Marin Jc, Bhoa R, Goadsby PJ. Flunarizine in migraine-related headache prevention: results from 200 patients treated in the UK. Eur J Neurol. 2018;25:811-817.
Background: Flunarizine is a calcium antagonist, which has been been used to prevent migraine for over 25-years. Although not licenced for use in the UK, it is widely used across Europe and Asia. It should be avoided in patients with depression and Parkinson's disease and related disorder.
Results: A cohort of 200 patients receiving Flunarizine was studied in patients with migraine-related headache, including new daily persistent headache with migrainous features. 76% of patients benefited. Doses up to 15mg/day were generally well tolerated, although 10.5% stopped due to adverse events. The most common adverse events were tiredness, mood change and weight gain.
Conclusions: There is evidence for use of Flunarizine in migraine.
For patients: NICE recognizes that Flunarizine is useful in migraine, but it remains unlicenced. GPs are therefore often unable to prescribe Flunarizine.
Dodick DW, Ashina M, Brandes JL, Kudrow D, Lanteri-Minet M, Osipova V, Palmer K, Picard H, Mikol DD, Lenz RA. ARISE: A Phase 3 randomized trial of erenumab for episodic migraine. Cephalalgia 2018;38:1026-1037.
Background: Calcitonin-Gene-Related-Peptide (CGRP) plays an important role in the pathogenesis of migraine. Erenumab is a fully human monoclonal antibody of the CGRP receptor. Blocking CGRP or its receptor has been shown to reduce migraine.
Results: Patients receiving Erenumab had less headache days per month than placebo (-2.9 vs -1.8). A higher proportion of patients receiving Erenumab also reported ≥ 50% reduction in monthly migraine days (39.7% vs 29.5%). Safety and adverse event profiles were similar for Erenumab and placebo.
Conclusions: Erenumab significantly reduces migraine frequency and appears to be safe.
For patients: Erenumab is currently being reviewed by NICE, but is unlikely to be available until 2019.