Do anti-CGRP drugs have a role in migraine aura therapy?

Matteo, Eleonora; Pensato, Umberto; Favoni, Valentina; Giannini, Giulia; Pierangeli, Giulia; Cevoli, Sabina

doi:10.1007/s00415-021-10546-1

Cited by 13 publications

(12 citation statements)

References 7 publications

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“…Given that aura is the clinical correlate of cortical spreading depression (CSD) mostly occurring before migraine pain, its reduction by anti-CGRP mAbs could indicate the ability of these biologics to change the neurochemical milieu within the migraineur’s brain. This interpretation is in keeping with a recent case report describing an immediate, complete and persistent response of aura to erenumab in a migraine patient otherwise resistant to classic preventatives (16). These findings therefore suggest that considering CGRP exclusively involved in the pain phase of migraine with aura is reductive.…”

Section: Discussionsupporting

confidence: 90%

“…Together, these neurochemical features suggest a role of the neuropeptide in sustaining dysfunctional neuronal excitation within the CNS, an event likely occurring in the migraineur's brain (31,32). Hints that anti-CGRP biologics affect CNS functions also stem from studies showing that erenumab counteracts migraine aura (16) and reduces trigeminal nociception-dependent activation of several migraineurs' brain regions (33,34). The ability of fremanezumab to sustain the brain descending pain inhibitory control pathway of mice (35) further suggest that these biologics can affect the migraine matrix.…”

Section: Discussionmentioning

confidence: 99%

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Effectiveness of anti-CGRP monoclonal antibodies on central symptoms of migraine

et al. 2022

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Background Clinical trials and observational studies with anti-calcitonin gene-related peptide antibodies poorly investigated their impact on migraine prodromal and accompanying symptoms. This information might help deciphering the biologics’ pharmacodynamic and provide hints on migraine pathogenesis. Herein, we report the effects of erenumab, fremanezumab and galcanezumab on attack prodromal and accompanying symptoms and on neurological and psychiatric traits. Methods An explorative, prospective, questionnaire-based study was completed by a cohort (n = 80) of patients with chronic migraine patients presenting a sustained reduction of ≥50% of Migraine Disability Assessment Score and ≥30% of monthly migraine days three months after anti-calcitonin gene-related peptide antibodies treatment. Results The majority of patients experienced a complete prevention of migraine symptoms without evidence of initial onset followed by attack abortion. Few patients reported the recurrence of prodromal (from 10% to 12.5%) or accompanying (from 1.3% to 8.8%) symptoms without headache. All patients with migraine with aura reported a decrease of aura incidence. Sleep changes (51.2%), increase in appetite (20.0%) and weight (18.8%) as well as a reduction in stress (45.0%), anxiety (26.3%), and panic attacks (15%) were also reported. Conclusion Anti-calcitonin gene-related peptide antibodies seems to significantly impact brain functions of migraineurs, preventing not only migraine headache but also its anticipatory and accompanying symptoms.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Effectiveness of anti-CGRP monoclonal antibodies on central symptoms of migraine

et al. 2022

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“…New data suggest that mAbs may have potential central properties, so they could influence CSD generation and the clinical manifestation of migraine aura, but the exact mechanisms remain unclear [ 22 , 23 , 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…It is only in responders’ patients that it induces a significantly reduced activation of the hypothalamus, a relevant central structure of migraine attack generation and chronification [ 23 ]. Moreover, Cevoli et al reported a case of a man affected by chronic migraine with aura who presented a dramatic drop of both migraine and aura frequency after the first injection of Erenumab 70 mg monthly, with persistent efficacy after 1 year [ 24 ]. However, lamotrigine was previously taken before starting Erenumab, so the potential additional functional effect of this medication could not be excluded.…”

Section: Discussionmentioning

confidence: 99%

Could the New Anti-CGRP Monoclonal Antibodies Be Effective in Migraine Aura? Case Reports and Literature Review

Albanese

Mercuri

2022

JCM

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Recently, monoclonal antibodies (mAbs) directed against calcitonin gene-related peptide (CGRP) (Eptinezumab, Fremanezumab, and Galcanezumab) or its receptor (Erenumab) have been approved for clinical use as prophylactic drugs for high-frequency episodic and chronic migraine. While their therapeutic effects on headache pain is well documented, there is scarce information on the usefulness of these medications in preventing migraine aura, which is believed to be associated with cortical spreading depression (CSD). Because of their large size, mAbs cannot easily cross the blood–brain barrier in high quantities, rendering the peripheral trigeminovascular system to likely be a major site of their action. In this paper, we report two cases of patients suffering from migraine with and without aura, who reported a complete disappearance of aura or reduced aura duration and intensity while taking Galcanezumab or Erenumab, respectively. Then, we present a brief overview of the literature about the controversial relationship between CSD and CGRP and about the potential “additional central” role of these mAbs in the pathophysiology of migraine aura.

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“…Moreover, CGRP might be directly involved in CSD activation. It has been demonstrated that anti-CGRP agents reduce aura frequency by acting on the trigeminal ganglion, which is rich in CGRP-expressing neurons ( 25 , 26 ). This supports our idea that exogenous CGRP acts directly on trigeminal ganglion, a region which is free of the blood brain barrier.…”

Section: Discussionmentioning

confidence: 99%

The Vasodilatory Response to CGRP of the Anterior and Posterior Cerebral Circulation in Migraine

et al. 2022

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IntroductionMigraine aura can be associated with headache or it may occur without one, which suggests an independent mechanism for the aura and for migraine headache. The role of CGRP in migraine headache is well established, but the connection between CGRP and the aura is still lacking an explanation. Exogenous CGRP can induce CGRP headaches and migraine auras in patients with migraine. The results of our recent study suggest differences in the vascular response to CGRP stimulation between migraine without aura and migraine with aura. Therefore, we hypothesized that the magnitude of the posterior cerebral circulation response in migraine with aura is greater than in migraine without aura and that CGRP stimulation has different effects on the anterior and posterior circulation in migraine with aura and migraine without aura.MethodsBy using transcranial doppler, we studied the hemodynamic effects of CGRP intravenous infusion at a rate of 1.5 mcg/min in 20 min on the mean arterial velocity in the middle cerebral artery and in the posterior cerebral artery in twenty patients with migraine and in a control group of twenty healthy subjects. The same CGRP effects on cerebral hemodynamics were analyzed separately for the group of patients with migraine with aura and the group of patients with migraine without aura. Fifteen patients with migraine (75%) had migraine without aura and 5 patients (25%) had migraine with aura.ResultsWe found that migraine has a significant impact on the vasodilatory response of the anterior (B = 4,249, SE = 1.023, r = 0.363, p < 0.001) and posterior cerebral circulation (B = 3.634, SE = 1.461, r = 0.227, p = 0.014). Migraine with aura was significantly associated with changes in the anterior (B = 2.558, SE = 0.880, r = 0.275, p = 0.005) and posterior cerebral circulation (B = 7.565, SE = 2,368, r = 0.359, p = 0.002), while migraine without aura was only significantly associated with changes in the anterior circulation. In addition, we established a significant impact of migraine with aura on VR PCA (B = 5.901, SE = 2,546, r = 0.291, p = 0.024).ConclusionWe conclude that TVR in the posterior cerebral circulation might be enhanced in MA and that aura might be a consequence of TVR enhancement.

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Do anti-CGRP drugs have a role in migraine aura therapy?

Cited by 13 publications

References 7 publications

Effectiveness of anti-CGRP monoclonal antibodies on central symptoms of migraine

Effectiveness of anti-CGRP monoclonal antibodies on central symptoms of migraine

Could the New Anti-CGRP Monoclonal Antibodies Be Effective in Migraine Aura? Case Reports and Literature Review

The Vasodilatory Response to CGRP of the Anterior and Posterior Cerebral Circulation in Migraine

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