Complex & Refractory Headache

In this issue of Practical Neurology, we discuss some of the most challenging headache disorders and complications. Migraine occurs in 12% of the population, with chronic migraine comprising 2%. According to the Global Burden of Disease study, migraine has the second highest disability worldwide in years lived with disability. Many patients have headache attacks that respond well to our first-line preventive and acute treatment, but an estimated 5% to 10% have headache disorders that do not respond to repeated trials of the various treatments available.

Although refractory headache is not a formal diagnosis, recommended criteria have been proposed for refractory chronic migraine that require an International Classification of Headache Disorders 3rd ed (ICHD-3) diagnosis of chronic migraine without medication-overuse headache and with medication failure of at least 5 preventive medication classes. Beyond refractory chronic migraine as it relates to treatment response, there are others way that migraine can be refractory and other types of headaches that can be refractory. Our first article on New Daily Persistent Headache (NDPH) by Dr Marmura is an example of a poorly understood headache disorder that is either self-resolving or extremely refractory.

The next article by Drs Alex and Armand describes Rational Polypharmacy for Migraine that does not respond to guideline-based preventive or acute treatments. This approach to combining therapies is just 1 consideration in the management of refractory migraine.

Next, Dr Blitshteyn provides a timely review of Headache in Dysautonomia & “Long COVID”/PASC as we frequently see worsening of underlying headache disorders and increasing new-onset headache after SARS-CoV-2 infection. The COVID-19 pandemic also highlights the poorly recognized subspecialty of autonomic medicine, which is being reported as part of the postacute sequelae of SARs-CoV-2 (PASC). Headache commonly coexists with dysautonomia, and, in that context, is often refractory to treatment. Research is limited, however, and guidelines are lacking. This article highlights these topics, often unfamiliar to neurologists.

Headache is not the only cause of disability in migraine. Aura and other symptoms, separate from pain, can be distressing, debilitating, and often hard to treat. Drs White and Ceriani discuss Migraine With Nonvisual Aura, and Drs Janssen and Metzler discuss Migraine Visual Aura & Other Visual Phenomena, including visual snow syndrome and Alice in Wonderland syndrome.

We complete our discussion with a focus on refractory headache in the acute setting, first with Status Migrainosus by Drs Duvall and Holdridge and Inpatient Headache Treatment by Drs Rhyne, Sattar, and Diamond, which covers criteria for admission as well as treatment once a patient has been admitted.

The treatment of refractory headache can be difficult for even the most seasoned headache neurologist. These patients form a large part of our practice and among the most disabled. The authors present an approach to difficult diagnoses like NDPH or COVID-19-associated disease, management of nonpain symptoms including aura, and expert opinion on acute and preventive treatment in both the outpatient and inpatient setting. Although diagnosis and treatment can be difficult, this series of excellent and practical articles can help guide clinical management in these challenging situations and help reduce the burden of illness in our patients.