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Recurrent Transient Global Amnesia Is More Common in Migraineurs

Article In Brief

Recurrent transient global amnesia—which generally lasts anywhere from four to six hours but can last up to 24 hours—was associated with an increased prevalence of personal and family history of migraine and earlier age at the time of onset.

Recurrent episodes of transient global amnesia (TGA)—a sudden, temporary episode of memory loss—are more likely in patients with a history or family history of migraine, according to what investigators believe is the largest study of its kind to date.

Mayo Clinic researchers found a personal history of migraine in 20 percent of patients with a single episode and 36.4 percent of those with recurrent episodes. A family history of migraine was documented in 167 patients (18.5 percent) with a single episode, and 44 individuals (30.8 percent) with recurrent episodes.

In a TGA episode, individuals cannot recall recent events or things that happened a day, a month, or even a year ago. Episodes typically resolve gradually over several hours.

In the new study, published online August 31 in JAMA Neurology, the rate of TGA recurrence was 13.7 percent. This is similar to rates reported in earlier studies. Individuals with single and recurrent episodes were comparable in age, gender, duration of anterograde amnesia, identifiable triggers, and electrodiagnostic findings, according to the report.

The investigators retrospectively examined records of all patients with TGA from August 1, 1992 to February 28, 2020—a total of 1,044 individuals. Nearly two-thirds of individuals with recurrent episodes had only a single recurrence, and more than 95 percent had three or fewer recurrences, further supporting the observation that multiple recurrences are rare, said lead author Ken A. Morris, MD, PhD, professor of neurology at Mayo Clinic in Rochester, MN.

“Episodes of TGA often have an identifiable trigger, such as the Valsalva maneuver, sexual intercourse, exercise, or strong emotion,” he said. These triggers support the prevailing notion that TGA may be caused by transient intracranial venous hypertension.

“To our knowledge, this is the largest analysis of individuals with recurrent episodes of TGA with sufficient power and follow-up to assess significant differences from individuals with isolated episodes of TGA,” he noted.

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“If diagnosed correctly, there is enough evidence to tell patients with a history or family history of migraine that there is a good likelihood that they will have additional events. In my experience, many have recurrent attacks. I tell them, ‘even if it happens, nothing will happen to them.’”—DR. LOUIS R. CAPLAN

In 2017, a population-based study of residents of Olmsted County, MN, found the recurrence rate was 14.4 percent, including 9.0 percent of individuals with episodes before and 5.4 percent of individuals with episodes after an index TGA event.

Last March, Australian researchers reviewed 93 prospective cases of TGA, including findings on diffusion-weighted imaging. They reported that 16 percent of patients experienced a recurrence of TGA. Although head injury was associated with 53 percent of these cases with recurrent episodes, DWI lesions were not significantly associated with outcomes.

Study Details, Findings

In the new analysis, a family history of TGA was identified in 12 individuals (1.3 percent) with a single episode of TGA and four individuals (2.8 percent) with recurrent episodes.

The number of recurrences ranged from one to nine; 137 individuals (95.8 percent) had three or fewer recurrences. The mean age at first episode of TGA was 65.2 years for individuals with a single episode and 58.8 years for those with recurrent episodes. There was no overall association between single or recurrent episodes and types of triggers, and no electroencephalographic findings were associated with an increased risk of TGA recurrence. Acute and subacute temporal lobe abnormalities were rare and did not require intervention.

No significant differences were seen in the proportion or types of triggers between individuals with single and recurrent episodes. However the same trigger often precipitated multiple TGA recurrences in individuals, suggesting a particular susceptibility and helping explain why certain patients had high numbers of recurrences, according to the authors.

For example, in the sole patient who had six TGA episodes, five were precipitated by intense straining due to singing, and two patients had four TGA episodes each, all precipitated by sexual intercourse.

The mean age of single first TGA episode was 65.2 years, but 58.8 years for recurrent events. The mean follow-up periods were 9.4 compared to 15 years for patients with recurrent episodes. The mean interval between an initial TGA episode and first recurrence was 4.1 years, 3.2 years for subsequent recurrences.

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“This study supports the migraine theory for recurrence, and this seems in agreement with my own experience. I have seen a few patients with multiple recurrences, and I have even treated empirically with antiepileptic agents, with some success, but only six patients in this study had more than three recurrences, so their population would not contribute evidence to the seizure etiology. Migraine is certainly one etiology, and this study is helpful in documenting that.”—DR. HOWARD S. KIRSHNER

“It is important for clinicians to be able to counsel patients on their risk of TGA recurrence, including any factors that may increase their likelihood of another event,” Dr. Morris said.

“The wide range of recurrence rates appears to reflect the variability of the strictness of the definition of TGA; higher rates are associated with more relaxed criteria for defining TGA,” he said. “These results can be used to counsel patients about risks of recurrence and may have implications for the understanding of TGA pathophysiology.”

Expert Commentary

“I generally agree with the findings. In my view, TGA is a syndrome, and it can be closely mimicked by migraine, partial seizure, or transient ischemic attack,” said Howard S. Kirshner, MD, FAAN, professor and vice-chair of neurology at Vanderbilt University Medical Center, in Nashville.

He said patients with a history of both migraine and seizure are likely to have a higher risk of recurrent attacks, and perhaps transient ischemic attacks, to a lesser extent.

“This study supports the migraine theory for recurrence, and this seems in agreement with my own experience. I have seen a few patients with multiple recurrences, and I have even treated empirically with antiepileptic agents, with some success, but only six patients in this study had more than three recurrences, so their population would not contribute evidence to the seizure etiology. Migraine is certainly one etiology, and this study is helpful in documenting that.”

Louis R. Caplan, MD, FAAN, professor of neurology at Beth Israel Deaconess Medical Center, said there is sufficient research evidence to help physicians answer patient questions and concerns if they have experienced a TGA event.

“I tell my patients that an episode is like a tape recorder running out of tape in the middle of a recording—there's nothing to be worried about,” he said.

“If diagnosed correctly, there is enough evidence to tell patients with a history or family history of migraine that there is a good likelihood that they will have additional events. In my experience, many have recurrent attacks. “I tell them, ‘even if it happens, nothing will happen to them.”

The most common precipitating events for TGA are physical activity, sudden temperature or atmospheric change, emotional stress, physical effort, and water contact/temperature change.

Dr. Caplan told Neurology Today that he has seen people experience TGA while engaged in higher-level mental activities, even while driving, without harming themselves or others.

In 1985, Dr. Caplan and colleagues published the first criteria for diagnosing TGA in the Handbook of Clinical Neurology. At that time, TGA criteria varied widely, and the published series included several patients with lasting neurological symptoms or memory loss, such as those observed in epilepsy or after head injury.

Under the criteria, diagnosis can be established under the following conditions: 1) anterograde amnesia is witnessed by an observer; 2) there is no clouding of consciousness or loss of personal identity; 3) cognitive impairment is limited to amnesia; 4) there are no focal neurological or epileptic signs; 5) there is no recent history of head trauma or seizures; 6) symptoms resolve within 24 hours; and 7) mild vegetative symptoms (headache, nausea, dizziness) may or may not be present during an acute episode.

Disclosures

Drs. Morris, Kirschner, and Caplan had no relevant disclosures.

Link Up for More Information

• Morris KA, Rabinstein AA, Young NP. Factors associated with risk of recurrent transient global amnesia https://jamanetwork.com/journals/jamaneurology/article-abstract/2770030#:~:text=Episodes%20of%20TGA%20often%20have,%2C%20exercise%2C%20or%20strong%20emotion.&text=These%20triggers%20support%20the%20prevailing,by%20transient%20intracranial%20venous%20hypertension. JAMA Neurol 2020; Epub 2020 Aug 31.
    • Arena JE, Brown RD, Mandrekar J, Rabinstein AA. Long-term outcome in patients with transient global amnesia: a population-based study https://www.mayoclinicproceedings.org/article/S0025-6196(16)30799-6/fulltext. Mayo Clin Proc 2017;92(3):399–405.
    • Tynas R, Panegyres PK Factors determining recurrence in transient global amnesia https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-020-01658-8#:~:text=Risk%20factors%20associated%20with%20recurrence,history%20of%20dementia%20(isolated%20vs. BMC Neurol 2020;20(1):83.