Inpatient headache admissions are often considered a last-case scenario option for patients with chronic refractory migraine. Initially described by Raskin,1 the admission typically consists of repetitive infusions of dihydroergotamine (DHE) with a pretreatment of antihistamine, neuroleptic, and other antinausea medications in addition to anti-inflammatory or steroid medications, IV fluids, and magnesium. Often this is superimposed on a continuous infusion of lidocaine or ketamine. One common concern is whether the use of DHE is safe for patients at a higher risk for vascular disease. Wang and colleagues reported on the incidence of cardiovascular adverse events in this population receiving repetitive intravenous DHE.
They present findings based on the Jefferson Headache Center (Philadelphia, Pennsylvania) Inpatient Headache Protocol, looking at patients admitted from January through October 2019. Of the 347 patients admitted during this period, 64 were identified as having either an elevated or low risk for atherosclerotic vascular disease. The degree of vascular risk was determined on the basis of an atherosclerotic cardiovascular disease calculation, using body mass index values, cholesterol level, and mean arterial blood pressure readings, as well as smoking and diabetes history. A score < 5.0% was designated low risk, while elevated risk included scores up to 20%. DHE was not offered to patients with a history of moderate to severe ischemic heart disease, coronary vasospasm, peripheral artery disease, Raynaud phenomenon, or ischemic stroke.
The primary outcome was treatment effectiveness, determined by an 11-point pain scale; secondary outcomes included tolerability, as defined by change in the patient's QTc (corrected QT interval) based on their daily ECG monitoring, the incidence of chest pain or shortness of breath, and whether DHE needed to be tapered or discontinued. The researchers noted that the elevated-vascular-risk group had fewer patients receiving the maximum dose of DHE and receiving less DHE over the course of their admission as compared with the low-risk group. They also reported lower response rates and less freedom from pain after admission. No clinically significant adverse events were noted in either group, and only three patients had sustained ECG changes from baseline.
DHE remains an effective treatment for the most chronic and refractory migraine cases, and it can be provided safely and effectively in an appropriately monitored setting. Although there still are contraindications for receiving DHE, those who can receive it may benefit significantly. Ideally, this should be done with cardiac clearance if there is any doubt regarding the vascular risk for any individual patient.
The frequency and severity of migraine can fluctuate due to a myriad of factors. When faced with worsening migraine, most healthcare providers ask their patients about specific triggers or other potential causes that may have led to the recent subacute worsening. Many healthcare providers will also investigate further, and when appropriate, order serum lab testing to determine whether any potential metabolic derangement, vitamin deficiency, or other abnormality could be contributing. Subclinical hypothyroidism is a common finding when investigating for these potential causes of worsening migraine, and often our internal medicine or endocrinology colleagues will discount these findings as "borderline" or still within normal limits. Dev and colleagues sought to determine whether low-dose thyroid replacement was beneficial for migraine prevention in this situation.
This study defined subclinical hypothyroidism as a thyroid-stimulating hormone (TSH) level of 4.5-10.0 mIU/L with a normal free thyroxine (T4), measured twice within 6 weeks for confirmation. Patients with prior thyroid disease were excluded from the study. Participants were randomly assigned to take 25 μg levothyroxine supplementation or placebo and were allowed to continue their migraine treatments. The primary outcomes were reduction in headache duration, frequency, severity, and Migraine Disability Assessment (MIDAS) score after 3 months.
A total of 87 patients with migraine and subclinical hypothyroidism were recruited, and the investigators noted a statistically significant improvement in all parameters (migraine frequency, severity, duration, MIDAS score) after 3 months of low-dose thyroid supplementation. This was maintained at a 3-month follow-up visit as well. TSH levels normalized in 87% of participants after repeat testing 3 months after the intervention.
When evaluating patients with worsening migraine who had been stable, it is wise to consider subclinical hypothyroidism as a potential etiology. Low-dose thyroid hormone supplementation appears to be well tolerated and effective for normalizing both TSH levels and, importantly, the migrainous exacerbation. Clinicians often will start or add preventive medications, ignoring the reason that there was an exacerbation in the first place, even though many of our colleagues choose not to treat this degree of hypothyroidism.
Many variants of migraine are better recognized and understood now; chief among these is vestibular migraine (VM). VM is a migraine subtype characterized by frequent or near-constant vestibular symptoms (vertigo, lightheadedness, disequilibrium, or rocking) with superimposed headache symptoms with some migrainous features. VM is generally considered to be more difficult to treat and more treatment-refractory than episodic or chronic migraine without vestibular symptoms. There are few treatments that are specific for this variant of migraine. Chen and colleagues sought to better understand the evidence of specific treatments for VM via meta-analysis.
Only randomized controlled trials were included in this meta-analysis; seven studies that specifically recruited patients with vestibular migraine using International Classification of Headache Disorders (ICHD) criteria were included. The outcomes of the studies were changes in frequency or severity of vestibular migraine attacks. The studies that were included were published from 2014 to 2022 and comprised multiple treatment comparisons, including metoprolol, venlafaxine, valproic acid, propranolol, flunarizine, a probiotic, and relaxation techniques.
Three interventions were noted to be significantly beneficial for VM prevention, specifically a decrease in migraine frequency: valproic acid, propranolol, and venlafaxine. Valproic acid yielded the greatest decrease in VM frequency among all interventions. None of the interventions were associated with improvement in VM severity, and none of the treatments were associated with significantly different adverse-event and dropout rates.
VM is widely thought to be underdiagnosed and should be considered more frequently. This includes situations in which the headache component of the patient's complaints is relatively mild but still associated with features of migraines, such as sensitivities to light and sound, nausea, or unilateral presentations of pain. There remain very few high-quality VM studies, but this meta-analysis should highlight potential treatment options and raise the profile for this diagnosis in order for further trials to be performed.
Additional Reference
1. Raskin NH. Repetitive intravenous dihydroergotamine as therapy for intractable migraine. Neurology. 1986;36(7):995-997. doi: 10.1212/WNL.36.7.995