Addressing Rare Headache Disorders: Acute Confusional Migraine

Clinicians are often confused by presentations of acute confusional migraine (ACM), a rare variant of migraine headache that manifests in symptoms of confusion, agitation, disorientation, altered mental status, and problems with speech and memory. ^1-3 These unique symptoms overlap with non-headache features of migraine both with and without aura, although ACM is not separately classified in the International Classification of Headache Disorders-3 Beta (ICHD-3β).

The main problem faced in ACM is the heterogeneity of symptoms. “I have seen a few profound cases of ACM,” Teshamae Monteith, MD, FAHS, chief of the headache division at the University of Miami, Miller School of Medicine, in Florida, told Neurology Advisor. She recalled a patient who could not find her way while driving home during ACM episodes. In another case, the patient was so agitated and incoherent that she was admitted to critical care, and did not recall the event. “More often, I see patients with more typical migraine (migraine with and without aura) with severe symptoms of ‘brain fog,’ which can be profoundly disabling,” she said.

ACM is reported to occur most often in children and adolescents, although cases in adults, often triggered by mild trauma, are well-described in the literature.^1-4 Dr Montieth observed that, “ACM is more common in the pediatric age range; however, adult onset may be a cause of unexplained transient neurological events in a person with a known history of migraine.”

A Challenging Diagnosis

ACM has been estimated to occur in 0.45 to 7.8% of the pediatric migraine population.^3,5 Overall, ACM has not been specifically studied and many clinicians remain unaware of the condition, which may result in under-diagnosis. Diagnosis of ACM is currently made by exclusion, as no criteria have been identified to classify it specifically as a migraine disorder.¹ The individual symptoms are often so unique as to point to a range of potential other causes including neoplastic, inflammatory, vascular, and metabolic disorders and transient global amnesia, all of which need to be ruled out first. “Initial presentation of ACM can be quite alarming and serious underlying neurologic conditions must be excluded,” said Frank Berenson, MD, FAHS, director, Atlanta Headache Specialists in Georgia. “Disorders such as acute stroke, meningitis/encephalitis, central nervous system inflammatory conditions, seizures, metabolic derangements, or acute drug/toxin exposures should be considered,” Dr Berenson told Neurology Advisor, adding that ACM cases are relatively rare and that he sees only a few each year in his practice.

“Initial diagnostic evaluation should include contrast[ed] MRI of the brain and MRA, lumbar puncture, EEG [electroencephalogram], and inflammatory and metabolic workup, as well as urine drug screen,”Dr Berenson said. According to a 2016 review of complicated migraines that he co-authored,² electroencephalograms performed during an episode frequently show diffuse slowing and sometimes intermittent delta activity in the frontal region, despite otherwise normal cerebrospinal fluid (CSF) findings and neuroimaging studies. In addition, Dr. Montieth pointed to the value of careful history, especially from a family member who may have witnessed the event.

Potential Causes

The most prominent theory of ACM suggests a similar pathophysiology to migraine aura, in which cortical spreading depression (CSD) reaches beyond the occipital region to the temporal, parietal, and frontal cortex; the brainstem; and the hippocampi to produce transient hypoperfusion that manifests in confusional symptoms. ^1-3 At least 50% of patients experience migraine headaches proximally to the ACM event, and many experience aura as well.^1,2

Dr Montieth collaborated on a 2018 review¹ that suggested that premonitory cognitive symptoms of migraine occurring hours or even days before the headache begins could fall under the description of ACM. At the same time, they also found evidence of a possible postdromal effect that may explain ACM, although studies of these effects did not specifically detail cognitive changes. Their review noted patients’ frequent descriptions of brain fog, along with feeling “hungover” or confused as postrdromal features of migraine headache.

Treatments

Due to the rarity of the condition, treatment of ACM is based on the clinician’s experience and insights. “There are no randomized placebo controlled clinical trials to guide clinicians,” Dr Montieth said, noting that “treating ACM with standard acute and preventive treatments seems reasonable.” She suggested that triptans should be used as first-line abortive treatment. Sodium valproate and propranolol have also been used, and prochloroperazine and topiramate, which is beneficial in the prevention of future ACM events, may be effective as well. 

Dr Berenson has a protocol he uses in his practice in Atlanta: “I typically recommend acute abortive therapy immediately at symptom onset with combination treatment including a triptan, a nonsteroidal anti-inflammatory, and an anti-dopaminergic agent. If symptoms progress despite [above] treatment, then more aggressive IV [intravenous] medication treatment in the ER setting is appropriate. IV valproic acid and prochlorperazine both have reported efficacy for ACM. For patients with recurrent ACM, I recommend initiation of daily preventive therapy with an anticonvulsant such as topiramate or valproic acid,” he said. 

Disclosures: Dr Montieth has served on the advisory boards for Supernus, Teva, Eli Lilly, and Electrocore. Dr Berenson reported no disclosures.

References

1. Farooqi AM, Padilla JM, Montieth TS. Acute confusional migraine: distinct clinical entity of spectrum of migraine biology. Brain Sci. 2018;8:29.
2. Blumenfeld AE, Victorio MC, Berenson FR. Complicated migraines. Semin Pediatr Neurol. 2016;23:18-22.
3. Schipper S, Riederer F, Sándor PS, Gantenbein AR. Acute confusional migraine: our knowledge to date. Expert Rev Neurother. 2012;12:307-314.
4. Gantenbein AR, Riederer F, Mathys J, et al. Confusional migraine is an adult as well as a childhood disease. Cephalalgia. 2011;31:206-212.
5. Verma R, Sahu R, Jaiswal A, Kumar N. Acute confusional migraine: a variant not to be missed. Brit Med J Case Rep. 2013:2013. doi:10.1136/bcr-2013-010504