Arteriovenous Malformations-Related Headache Identification, Treatment

Brain arteriovenous malformations (AVMs) affect approximately 0.1% of the population and are associated with chronic headache in a portion of these individuals.¹ The mechanisms underlying the link between unruptured AVM and headache are unclear, and it is difficult to differentiate AVM-associated headaches with headaches of other origins.^2,3

“It is important to emphasize that while AVM patients may present with headache, a very small percentage of patients evaluated for headache actually have an AVM,” David K. Kung, MD, an assistant professor of neurosurgery at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, told Neurology Advisor. In a study of patients with normal neurologic findings, neuroimaging resulted in AVM diagnosis in only 0.2% of cases.⁴

In addition, most patients with AVM do not experience headaches, although “some have daily headaches localized to a specific area of the head that suggests they are caused by the AVM,” said Rafael Tamargo, MD, the Walter E. Dandy professor of neurosurgery and director of cerebrovascular surgery at Johns Hopkins University School of Medicine in Baltimore, Maryland. If a left frontal AVM presents with headache localized to the left forehead and eye, for example, that is a strong indication that the pain is related to the AVM, as is the remittance of pain upon treatment of the AVM, he explained in an interview with Neurology Advisor.

Etiology

With a ruptured AVM, headache may result from pressure in or around the brain and from irritation from blood byproducts, said Dr Tamargo. The etiology of pain due to unruptured AVM is less evident, though it has been proposed that “stretching of arterial nerve endings may cause headache, similar to dilation of the vessels with migraine,” and “another possible cause is abnormal blood flow through the AVM bed,” he told Neurology Advisor.

Several mechanisms involving trigeminovascular activation are often proposed in the literature as mechanisms underlying nonhemorrhagic headache in patients with AVM:

• Increased intracranial pressure (ICP) is believed to possibly trigger headache by activating the trigeminal system at high pressures.⁵ Findings suggest that the buffering capacity against ICP may become overwhelmed due to the AVM, and patients with headache may be hypersensitive to small increases in ICP.^6,7 “Thus, the ICP waves associated with AVM may simply act as a trigger in sensitive migraineurs,” wrote Ellis, et al in a recent review on the topic.⁸
• Steal phenomena from the high-flow arteriovenous shunting in AVM may lead to headaches. This concept is controversial, however, and findings have been mixed. In a study using computed tomography (CT) scanning, for example, impaired local cerebral blood flow (CBF) improved substantially following AVM resection.⁹ Other results, however, do not support ischemic steal as a contributor to AVM symptoms.¹⁰
• Cortical spreading depression (CSD) may lead to headache via alterations within the meningeal vessels and resulting activating of the trigeminovascular system.¹¹ “Given that alterations in regional rCBF [regional cerebral blood flow] in the visual cortex may be in part responsible for migraine with aura, a mechanistic association with occipital AVM can be postulated,” noted Ellis and colleagues. “It is conceivable that transient alterations in rCBF initiated by CSD within the occipital lobe secondary to AVM may cause headache and visual symptomatology.”⁸

Diagnosis and Treatment

AVM-associated headache may or may not present with other symptoms. “Intractable, unilateral headache should increase suspicion for brain AVM and prompt [magnetic resonance imaging] MRI evaluation,” according to the review.⁸ According to the International Classification of Headache Disorders (ICHD-3) diagnostic criteria for AVM-related headaches, they “have a clinical course that parallels that of a coexisting AVM in terms of temporality, severity, and location.” 

The most well-known example is occipital AVM, which is believed to be a risk factor for headache. Headache occurs in patients with occipital AVM at rates ranging from 15% to 61%, and it is often characterized by visual symptoms such as field cuts and blurring, as well as other migraine-like symptoms.^12-14

If AVM is detected, the Spetzler-Martin grading system can help estimate risk and guide treatment selection, which is influenced by the size, location, blood vessel supply, and drainage of the AVM. Grading is based on a 1 to 5 scale, with 1 representing the simplest cases and 5 representing the most complex cases. A 2010 study observed surgical risk levels ranging from 0.7% (95% CI, 0%-3%) in grade 1-2 AVMs to 21% (95% CI, 15%-28%) in grade 3-5 AVMs.¹⁵

If lesion eradication is identified as the treatment goal, it may be achieved by several methods. Various “case series have shown that intervention for AVM with microsurgical resection, endovascular embolization, stereotactic radiosurgery, or a combination of these can be effective in decreasing or even eliminating headaches –however, there could be bias in case reporting,” said Dr Kung.

• Microsurgical resection, embolization, or both led to significant or complete headache improvement across a number of studies in 39% to 100% of patients.^16,17
• Radiosurgery shows improvement rates ranging from 47% to 75% across numerous studies, including a retrospective study demonstrating a 69.5% headache reduction 5 years after radiosurgery for AVM.^18-20
• Multimodal treatment, such a combination of surgery, embolization, and/or radiosurgery embolization, was associated with improvement in 50% to 67% of cases in earlier research, and the improvement rate was 87.8% in a new study of multidisciplinary care for AVM-associated headache.²¹  

Future Directions

Research on AVM has mainly focused on hemorrhage risk vs treatment risk, as well as seizure control, rather than headache. “There is a lot we don’t know about AVM-related headache,” said Dr Kung. “I believe that the next step should be to study the effect of pharmacological agents on achieving headache relief for unruptured AVM, targeting each hypothetical mechanism.” 

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References

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This article originally appeared on Neurology Advisor