Navigating migraine care through the COVID-19 pandemic: an update

DOI: https://doi.org/10.1007/s00415- 021- 10610- w

Abstract-Summary The worldwide treatment gap for migraine before COVID-19 inevitably widens as attention focuses on an international emergency.

This article examines the impact of COVID-19 on migraine, and changing

aspects of migraine care during and after the pandemic.

Most migraine treatments can start or continue in acute COVID-19, with care to

avoid drug interactions.

Secondary effects of COVID-19, including long COVID and its economic

impact, are probably equal or greater in people with migraine.

Migraine and other long-term conditions need adequate resourcing to prevent

personal, social and economic suffering.

Treating migraine, a sequel of COVID, potentially reduces the impact of

long COVID.

Introduction Challenges for health practitioners and physicians and neurologists include protec- tion of vulnerable patients, and tackling neurological complications of COVID-19. Pro-active management of long-term conditions, such as migraine and epilepsy [206], is essential to prevent suffering, secondary morbidity, particularly mental health problems, and avoidable emergency attendances [206–209].

A World Health Organization (WHO) survey of 155 countries found that almost half of patients with chronic diseases missed their regular medical care and medica- tions since COVID-19 pandemic began [210].

COVID-19 Risks in People with Migraine There are little specific data on migraine as a risk factor for COVID [211].

Extrapolation suggests people with migraine are at average, or lower risk, of

severe acute COVID-19.

Prevalence of migraine in younger women militates against two of these risk

factors.

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A UK study found migraine was most common in white women, without correla- tions with education or income [212] and a global review found headache disorders did not follow sociodemographic indices [208].

The Effects of COVID-19 on Migraine There is little to differentiate worsening of pre-existing migraine from headaches described with COVID-19 reported in 13% of a hospitalized Wuhan cohort [213] or later studies [214, 215].

Most reports with large sample size are broad-brush, lacking the granularity to differentiate whether these are migraine exacerbations, new migraine, non-specific headache associated with fever [213, 214, 216, 217], or permutations of all three.

A Turkish web-based survey found headache in those with COVID-19 were associated with anosmia, ageusia and gastrointestinal complaints, as expected for the COVID-19 disease phenotype, but not necessarily indicative of a causal or spe- cific relationship.

One study of headache in acute COVID found one-third had pre-existing

migraine [218] but others report no link [219].

Headaches with COVID-19 in migraineurs were different from their usual head-

ache in 92% of 25 studied, usually holocranial and pressing [220].

Phenotypic variations in migraine and other primary headaches are well described

clinically including in individual patients [221, 222], and genetically [223].

Remote Consultations in Current Migraine Care Phone, video, online, and “e-consults” reduce direct COVID-19 risk to migraine patients and professionals [224].

Remote medicine is here to stay, encouraged by governments, as it is cost saving,

and effective when used well.

Benefits beyond COVID include patient convenience; and saved travel, time,

financial and environmental costs.

Problems include inability to fully examine, “digital exclusion” of vulnerable patients, and reduced non-verbal communication, particularly reduced ability to gauge mood [225].

Missing the Diagnosis of Secondary Headache This is a fear for both patients and healthcare workers, but the risk of missed brain tumours or other sinister causes of headache in remote consultations is low with a previous diagnosis of migraine and no change in headache features [76].

Variations on migraine not conforming to consensus definitions are sometimes tricky, such as migraine aura without headache presenting with tingling, dizziness or visual symptoms [226], all of which have a wide differential diagnosis.

Most can be picked up remotely through systematic questioning (for example sudden onset, worsening or visual symptoms, scalp and temporal tenderness, jaw claudication) and patient access to thermometers and home sphygmomanometers aid assessment.

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COVID-19 and SARS-COV2 Vaccines

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In people with headache, elevated BMI and visual symptoms, urgent ophthalmo- logical assessment is needed, looking for idiopathic intracranial hypertension as headache features may overlap with migraine [227].

[Section 6] There is no evidence that triptans, paracetamol or aspirin increase the risk of COVID-19.

Reports of four French COVID-19 patients taking ibuprofen with poor outcomes (Level 4 evidence) [228] triggered authorities to advise paracetamol instead of NSAIDS or aspirin for COVID-19-related fever.

Ibuprofen increases angiotensin-converting enzyme-2 (ACE-2) bioavailability, a binding site for COVID-19, and could potentially enhance initial infectivity, based on extrapolations from animal studies in cardiac muscle using sevenfold the weight- adjusted doses for humans [229].

Informed patients can decide on ibuprofen and aspirin for their acute migraine,

given the lack of definitive data.

[Section 7] Beta-blockers, low-dose aspirin (75 mg daily), pizotifen, and self-injected calcito- nin gene-related peptide (CGRP) antagonists can be safely used during the pan- demic, with no evidence that they increase COVID-19 risk or mortality.

Anti-epileptic drugs, also used on- and off-label for migraine and mood disor- ders, have no known impact on COVID-19 risks, but there are some cautions in migraineurs developing acute COVID while taking them.

Gabapentin and pregabalin do not increase the risks of acute COVID-19, but may

cause over-sedation [230].

In older people, a study found a 1.6-fold increased risk of pneumonia on anticho-

linergic medication including amitriptyline or nortriptyline [231].

A recent population-based study in 1.4 million people found no increased mor-

tality in COVID-19 patients taking ARBs and ACE inhibitors [232].

Treating Migraine in Pregnancy During COVID-19 Only 8% of migraineurs worsen during pregnancy [233].

Propranolol, tricyclic antidepressants and low-dose aspirin (75–83 mg) remain

suitable [234].

Potential Treatments of COVID-19 Relevant to Migraine: Interactions and Repurposing Several migraine preventive therapies have been postulated from first principles and bioinformatics [235] as treatments for COVID-19.

Injection of SARS-CoV spike protein into mice worsens acute lung failure in vivo that can be attenuated by blocking the renin-angiotensin pathway, suggest- ing that ARBs and ACE-I are a potential therapy to prevent the cytokine storm and acute respiratory distress syndrome associated with severe COVID-19 [236, 237].

Low-dose botulinum toxin may also attenuate the COVID-19 hyper- inflammatory response, attenuate cough and acute respiratory failure, but this is speculative at the current time [238].

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Potential acute anti-viral treatments and vaccination may trigger acute migraine,

but there is no evidence they exacerbate migraine long-term [239, 240].

Strategies for Migraine During Acute and Long COVID We face the medical and social consequences of COVID and its aftermath for peo- ple with migraine.

Many people with migraine have increased depression and anxiety during COVID and treatment of this is critical to avoid a vicious spiral of worsening mental health and migraine [218].

Systematic reviews found headache in 38–44% of patients with long COVID [241, 242], and migraine and other headaches are frequent postdromes of viral ill- ness [243] and part of chronic fatigue syndromes in 84% [244].

Treating associated migraine will potentially reduce the burden of long COVID.

Conclusions Current acute migraine treatments with paracetamol and triptans; and preventive treatments with pizotifen, beta-blockers, CGRP antagonists and e-TNS, can be safely started or continued during COVID.

Care is needed with antiepileptic and tricyclic drugs used for migraine, which

may cause sedation, renal and fluid imbalance in acute COVID-19.

The minority of people with severe migraine unresponsive to standard treatments

should be offered CGRP antagonists rapidly and without bureaucratic fuss.

Migraine is a treatable component of long COVID, warranting rapid research

and resources.

Acknowledgement A machine generated summary based on the work of Angus-Leppan, Heather; Guiloff, Angelica E.; Benson, Karen; Guiloff, Roberto J. 2021  in Journal of Neurology.

Coronavirus disease-19 and headache; impact on pre-existing and characteristics of de novo: a cross-sectional study