By Dara Jamieson, MD

Assistant Professor of Clinical Neurology, Weill Cornell Medical College

Dr. Jamieson reports she is on the stroke adjudication committee for Bayer and is a consultant for Boehringer-Ingelheim.

Synopsis: During an attack of migraine without aura, patients may experience transient cognitive impairment, with predominant involvement of verbal processing speed, learning, and memory, due to reversible cortical dysfunction.

Source: Gil-Gouveia R, et al. Cognitive dysfunction during migraine attacks: A study on migraine without aura. Cephalalgia 2015;35:662-674.

Patients often report a sense of confusion and impaired thinking during migraine attacks, including immediately before and after the head pain, but studies designed to validate these observations have produced inconsistent results. The authors used a comprehensive battery of cognitive and behavioral tests to investigate changes in cognitive performance of migraineurs during attacks of migraine without aura. The only allowed daily medications were oral contraceptives and migraine prophylactics, and treatment with acute pain medication was not permitted. This prospective randomized, crossover study compared the within-subject neuropsychological evaluations during a naturally occurring untreated migraine attack and also during a headache-free period. Half the subjects were tested first during the attack, and half were first tested during the headache free-period. There was at least a month between testing during the migraine attack and during a headache-free period to avoid learned testing proficiency. Patients were evaluated with the Headache Impact Test and the Migraine-Specific Quality of Life questionnaires and with the Zung Depression scale and the State-Trait Anxiety Inventory. Pain intensity was scored with a 10-point visual analog scale. Paper and pencil neuropsychological testing was applied by licensed neuropsychologists using a standard battery of tests to test executive functioning, long-term memory, perception, motor control, and language.

Out of 39 patients with episodic migraine without aura (37 females, average age 38 years), 24 completed the study with evaluation at both times. Seven participants (29%) were on preventive medication (two propanolol, two propanolol and amitriptyline, two amitriptyline, and one topiramate and amitriptyline). Migraine impact was moderate to high, with most participants having one to four attacks monthly, with moderate to severe pain intensity. Migraineurs performed worse during the attack of head pain and accompanying symptoms in the majority of cognitive tests, compared to their headache-free period. Testing during the headache periods was impaired in reading and processing speed (word reading speed, P = 0.013) as well as verbal memory and learning short-term verbal recall with (P = 0.01) and without (P = 0.013) semantic cueing and delayed recall with (P = 0.003) and without (P = 0.05) semantic cues. Differences found in cognitive performance during a migraine attack were unrelated to patient baseline characteristics, including age, gender, literacy, condition order, the interval between the two evaluations, anxiety, pain intensity, or duration of the attack. The authors considered potential mechanisms by which cognitive impairment occurs during an attack of migraine without aura, including a cortical spreading depression — like phenomena, activation of the raphe nuclei and its cortical serotoninergic projections, or activation of the thalamus, with its effect on perception, learning, and cognition.


Commentary

Patients’ complaints of transient difficulty with verbal and memory processing during a migraine without aura have been validated by this well-designed study. However, the sample size was very small and the patients were mostly female, within a restricted age range, not representing the complete spectrum of migraine sufferers. Confounding conditions, including the effect of pain per se and of the accompanying gastrointestinal symptoms and environmental sensitivities, have not been completely eliminated in this study. The authors point out that the findings could be induced by the cognitive processes related to the head pain, as opposed to an effect unique to migraine. Neuropsychological changes, with impairment in cognitive function, can be associated with chronic pain with resultant neurochemical and anatomic cerebral changes. Patients in this study had to suffer their migraine attacks without pain relief, as attacks treated with abortive medication in the previous 12 hours were not eligible for investigation in this study. Cognitive functioning needs to be assessed in patients who are taking triptans for acute pain treatment, a real-world environment. Because some daily medications used to decrease the frequency and severity of migraine headaches are well known to have cognitive side effects, further investigation should be restricted to patients who are not on oral preventive medications. The argument could be made that these medications, especially topiramate, could cause decreased memory and verbal fluency equally during the attack and during headache-free periods. However, as side effects vary according to dose escalation, these medications could have a differential effect on cognition over time. Despite the study limitations, the conclusions validate patient experiences. Migraine patients with cognitive complaints during a migraine attack without aura should be advised to avoid bar and board examinations during a headache, and other intellectual challenges, adding to the disability of the attack, as well as to anticipatory anxiety.