[Show abstract][Hide abstract] ABSTRACT: Single pulse transcranial magnetic stimulation (sTMS) is a novel treatment for acute migraine. Previous randomised controlled data demonstrated that sTMS is effective and well tolerated in the treatment of migraine with aura. The aim of the programme reported here was to evaluate patient responses in the setting of routine clinical practice.
Migraine patients with and without aura treating with sTMS had an initial review (n = 426) and training call, and then participated in telephone surveys at week six (n = 331) and week 12 during a 3-month treatment period (n = 190).
Of patients surveyed with 3 month data (n = 190; episodic, n = 59; chronic, n = 131), 62 % reported pain relief, finding the device effective at reducing or alleviating migraine pain; in addition there was relief reported of associated features: nausea- 52 %; photophobia- 55 %; and phonophobia- 53 %. At 3 months there was a reduction in monthly headache days for episodic migraine, from 12 (median, 8-13 IQ range) to 9 (4-12) and for chronic migraine, a reduction from 24 (median, 16-30 IQ range) to 16 (10-30). There were no serious or unanticipated adverse events.
sTMS may be a valuable addition to options for the treatment of both episodic and chronic migraine.
The Journal of Headache and Pain 12/2015; 16(1):535. DOI:10.1186/s10194-015-0535-3 · 2.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hemicrania continua (HC) is a rare chronic headache disorder, typically accompanied by cranial autonomic features and responding to therapeutic doses of indomethacin. The pathophysiology of hemicrania continua is not fully understood.
We report a series of three patients who developed a continuous hemicranial headache after cranial surgery. Each case presented a similar phenotype of continuous half-sided headache, cranial autonomic symptoms with exacerbations (2/3), and a response to indomethacin.
The biology of hemicrania continua may be activated post-craniotomy just as can be seen with other primary headache disorders.
The Journal of Headache and Pain 12/2015; 16(1):526. DOI:10.1186/s10194-015-0526-4 · 2.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Migraine attacks may present different features in different patients and also within the same patient. The percentage of patients reporting stereotyped attacks and those reporting attacks with different phenotypes has not been the object of specific investigations.
The objective of this article is to evaluate the percentage of migraine patients reporting the same characteristics, in terms of phenotype and response to symptomatic medications on three consecutive migraine attacks.
Thirty patients with migraine without aura prospectively recorded the features of three consecutive attacks in a headache diary. Characteristics recorded were: pain intensity, presence of nausea, vomiting, photophobia, phonophophia, osmophobia, allodynia, cranial autonomic symptoms (at least one), and premonitory symptoms. Patients were allowed to take frovatriptan as symptomatic medication, whose efficacy was evaluated as the two hours pain-free status.
None of the patients presented identical characteristics on the three studied attacks. This was still the case if we reduced the number of variables evaluated from 11 to seven of the eight core features indicated by the ICHD. Considering just six variables: unilaterality and quality of pain, presence/absence of nausea, vomiting, photophobia and phonophobia, only two patients (6%) had identical features on three consecutive attacks.With respect to the response to frovatriptan, 39% of patients had the same response, either positive (i.e. pain free after two hours) or negative (i.e. not pain free after two hours) on three consecutive attacks.
Migraine attacks show a high variability not just among patients, but also within the same patient. Our data indicate that stereotypy of attacks is uncommon, and reinforces the underlying logic of the current operational classification system.
[Show abstract][Hide abstract] ABSTRACT: The thalamus contains third-order relay neurons of the trigeminal system, and animal models as well as preliminary imaging studies in small cohorts of migraine patients have suggested a role of the thalamus in headache pathophysiology. However, larger studies using advanced imaging techniques in substantial patient populations are lacking. In the present study, we investigated changes of thalamic volume and shape in a large multicenter cohort of patients with migraine. High-resolution T1-weighted MRI data acquired at 3 tesla in 131 patients with migraine (38 with aura; 30.8 ± 9 years old; 109 women; monthly attack frequency: 3.2 ± 2.5; disease duration: 14 ± 8.4 years) and 115 matched healthy subjects (29 ± 7 years old; 81 women) from four international tertiary headache centers were analyzed. The thalamus and thalamic subnuclei, striatum, and globus pallidus were segmented using a fully automated multiatlas approach. Deformation-based shape analysis was performed to localize surface abnormalities. Differences between patients with migraine and healthy subjects were assessed using an ANCOVA model. After correction for multiple comparisons, performed using the false discovery rate approach (p < 0.05 corrected), significant volume reductions of the following thalamic nuclei were observed in migraineurs: central nuclear complex (F(1,233) = 6.79), anterior nucleus (F(1,237) = 7.38), and lateral dorsal nucleus (F(1,238) = 6.79). Moreover, reduced striatal volume (F(1,238) = 6.9) was observed in patients. This large-scale study indicates structural thalamic abnormalities in patients with migraine. The thalamic nuclei with abnormal volumes are densely connected to the limbic system. The data hence lend support to the view that higher-order integration systems are altered in migraine.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 10/2015; 35(40):13800-13806. DOI:10.1523/JNEUROSCI.2154-15.2015 · 6.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The pathogenesis of migraine is not well understood. To dissect the relative contributions of endogenous peripheral and central mechanisms in triggering migraine, we examined the effects of two pharmacologically similar, but clinically different, vasodilator neuropeptides, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide 38 (PACAP-38), on dural meningeal vessels and the response properties of central trigeminovascular neurons. Both VIP and PACAP-38 caused short-lived meningeal vasodilation mediated by VPAC2 receptors, which did not coincide with activation of central trigeminovascular neurons. Only PACAP-38 caused delayed activation and sensitization of central trigeminovascular neurons, similar to its delayed effects in inducing migraine headache. After a 90-min delay, PACAP-38 induced a robust increase in ongoing spontaneous firing and hypersensitivity to intra- and extracranial somatosensory stimulation, which did not coincide with meningeal vasodilation. Only intravenous delivery of a PAC1 receptor antagonist inhibited the peripheral meningeal vasodilatory effects of dural trigeminovascular nociception, whereas only central (intracerebroventricular) administration of the PAC1 receptor antagonist inhibited dural nociceptive-evoked action potentials in central trigeminovascular neurons. Our data suggest that the endogenous mechanisms of migraine pathogenesis are located within the central nervous system, likely in the trigeminocervical complex, and that the dural meninges and their primary afferent innervation are less likely to contribute to migraine initiation. Furthermore, the PAC1 receptor may be an appropriate molecular target for migraine therapeutics.
Science translational medicine 10/2015; 7(308):308ra157-308ra157. DOI:10.1126/scitranslmed.aaa7557 · 15.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The management of patients with migraine is often unsatisfactory because available acute and preventive therapies are either ineffective or poorly tolerated. The acute treatment of migraine attacks has been limited to the use of analgesics, combinations of analgesics with caffeine, ergotamines, and the triptans. Successful new approaches for the treatment of acute migraine target calcitonin gene-related peptide (CGRP) and serotonin (5-hydroxytryptamine, 5-HT1F) receptors. Other approaches targeting the transient receptor potential vanilloid (TRPV1) receptor, glutamate, GABAA receptors, or a combination of 5-HT1B/1D receptors and neuronal nitric oxide synthesis have been investigated but have not been successful in clinical trials thus far. In migraine prevention, the most promising new approaches are humanised antibodies against CGRP or the CGRP receptor. Non-invasive and invasive neuromodulation approaches also show promise as both acute and preventive therapies, although further studies are needed to define appropriate candidates for these therapies and optimum protocols for their use.
The Lancet Neurology 09/2015; 14(10):1010-22. DOI:10.1016/S1474-4422(15)00198-2 · 21.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patients with visual snow complain of uncountable flickering tiny dots in the entire visual field similar to the view of a badly tuned analogue TV channel (TV snow). The symptoms are often continuous and can persist over years. This condition is grouped among the persistent visual phenomena in migraine, although it clinically presents a unique entity distinct from persistent migraine aura or migraine aura status. Here, we review the recent literature leading to the identification of the visual snow syndrome. The additional visual and non-visual symptoms are described in detail, and criteria are presented for future studies. Using these criteria, the relationship to migraine and typical migraine aura was recently evaluated. Further, patients with visual snow differ from controls in respect of hypermetabolism in the supplementary visual cortex (lingual gyrus). This provides evidence that visual snow, despite being purely subjective in the individual patient, has a clear biological basis. The area of hypermetabolism overlaps with the functional correlates of photophobia in migraine supporting the close relationship of migraine and visual snow.
Current Pain and Headache Reports 06/2015; 19(6):497. DOI:10.1007/s11916-015-0497-9 · 2.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Neuroimaging techniques can be used to investigate both functional and structural features of the brain in patients who have primary headache disorders such as migraine or cluster headache. Improved treatments are needed for both, and this goal will likely be facilitated by a better understanding of the underlying biology. Functional imaging studies have identified regions active during attacks, as well as abnormalities that are present during the interictal period. Volumetric, surface-based morphometric, and tractography studies have revealed structural changes, although whether these represent a cause or effect of the condition remains to be determined. The development of new techniques and modalities promises to yield additional insights in the future. This article aims to review the major findings and most recent advances in neuroimaging of migraine and cluster headache.
Current Pain and Headache Reports 06/2015; 19(6):487. DOI:10.1007/s11916-015-0487-y · 2.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Addressing the overuse of acute medicines
is a challenging but crucial component of migraine treatment
in clinical practice. sTMS has previously shown efficacy
in reducing migraine symptoms and acute medicines
in the UK pilot programme.
Aim: To explore the utility of sTMS to treat migraine with
acute medication overuse.
Method: Patients (n¼28) were selected by their
Neurologist in open clinical practice and advised to reduce
their intake of acute medicines. Headache nurses provided
treatment instructions and collected baseline and outcome
data through telephone surveys at Baseline, 6- and 12- week
time points. The patients were instructed to treat with sTMS
twice daily and acutely at attack onset, using the sTMS
Medical Advisory Board (TMS-MAB) guidelines. Patients
were encouraged to reduce acute medicines during the
treatment period; a rate of reduction was not stipulated.
Results: Twenty-eight patients were prescribed sTMS and
treated for 12 weeks. Of these: 86% (n¼24) reported a
reduction in the number of days of acute medicine use,
with 75% (n¼21) reporting reduced pain severity.
Nineteen patients (68%) reported reduced migraine days
and 15 (54%) had shorter attack duration. In addition,
headache disability scores (HIT-6) were improved in 75%
of patients (n¼21). The treatment was well tolerated and
no adverse events were reported.
Conclusion: sTMS may be an effective bridge treatment
for patients with medication overuse. The majority of
patients reduced acute treatments and reported efficacy
for migraine symptoms.
[Show abstract][Hide abstract] ABSTRACT: Migraine is a complex disorder of the brain that is common and highly disabling. As understanding of the neural pathways has advanced, and it has become clear that the vascular hypothesis does not explain the disorder, new therapeutic avenues have arisen. One such target is calcitonin gene-related peptide (CGRP)-based mechanisms. CGRP is found within the trigeminovascular nociceptive system widely from the trigeminal ganglion to second-order and third-order neurons and in regulatory areas in the brainstem. Studies have shown CGRP is released during severe migraine attacks and the reversal of the attack with effective triptan treatment normalizes those levels. CGRP administration triggers migraine in patients, and CGRP receptor antagonists have been shown to abort migraine. Here, we review the current state of CGRP mechanism antagonist therapy as its research and development is increasing in migraine therapeutics. We discuss several recent trials, highlighting the evidence base behind these novel drugs, and their potential future contribution to migraine management.
Current Neurology and Neuroscience Reports 05/2015; 15(5):547. DOI:10.1007/s11910-015-0547-z · 3.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Migraine is a common, complex disorder of the brain with significant morbidity. As the pathophysiology of the disorder has become better appreciated, the role of neuropeptides has been explored. Calcitonin gene-related peptide (CGRP) has emerged as a promising therapeutic target.
CGRP is widely distributed in the nervous system, particularly at anatomical areas thought to be involved with migraine, including the trigeminovascular nociceptive system. In studies, CGRP has been shown to be released during severe migraine attacks, and effective triptan treatment of an attack normalizes these levels. CGRP administration triggers migraine in patients and CGRP receptor antagonists can abort migraine. Moreover, recent data demonstrate that CGRP mechanism blockade either by small molecule receptor antagonists or by monoclonal antibodies can have a preventive effect in migraine.
This article highlights the evidence behind the role of CGRP in migraine and the state of CGRP-based mechanism treatment development. We present a summary of the evidence base behind CGRP in migraine pathophysiology and the novel CGRP mechanism drugs and their potential future contribution to migraine management in our clinical practice.
Current opinion in neurology 04/2015; 28(3). DOI:10.1097/WCO.0000000000000191 · 5.31 Impact Factor