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Add Seizures to the Risks Associated with E-Cigarettes/Vaping
FDA Urges Vigilance and Reporting in Alert to Clinicians

Article In Brief

The US Food and Drug Administration is seeking more information about seizures that are possibly linked to vaping. Officials and neurologists discuss what's known at this point about the risk for seizures and other complications.

As federal and state public health officials scramble to respond to the emergence of severe lung problems, including deaths, among users of e-cigarettes and “vaping” devices, the US Food and Drug Administration (FDA) announced that more than 100 seizures and other neurological problems linked to the devices have been reported to the agency over the last decade.

In late August, the agency said that they had received 127 such reports since 2010, but that too little data are available to draw any conclusions yet. In its alert, the FDA urged neurologists and other health care providers to be vigilant and ask patients about their use of the devices for nicotine or marijuana when presented with neurological symptoms of seizure or other sudden neurocognitive issues.

What stands out in the FDA's list of neurological cases is the relative youth of the subjects, the lack of any prior seizure history, and their exposure to much higher levels of nicotine than with products like cigarettes or chewing tobacco. Last April, the agency said that it had received reports of seizures occurring in first-time e-cigarette users as well as in those with more experience, and some have occurred “after a few puffs or up to one day after use.”

In interviews with Neurology Today, several neurologists said they had seen patients with these suspected complications, which underscores how important it is for clinicians to be on the look-out for these potential sequalae, and to learn to screen for substance use in a nonjudgmental way.

Acting FDA Commissioner Norman Sharpless, MD, in the agency's August statement, said, “Although we still don't have enough information to determine if e-cigarettes are causing these reported incidents...we strongly encourage the public to submit new or follow-up reports with as much detail as possible. It is imperative that health care professionals, consumers, parents, teachers and other concerned adults, as well as youth and young adult users, report detailed information about any past or future incidents of seizures following e-cigarette use to the FDA.”

The reports over the last 10 years do not necessarily indicate an increase in frequency or prevalence of such incidents, the FDA said, adding that some users reported other serious neurological symptoms such as fainting or tremors, which may or may not be related to seizures.

Submitting follow-up reports containing test results and information about whether the symptoms have stopped or continued, with or without tobacco product use, is very important to understand possible causes, the FDA said. Health care professionals assessing neurological symptoms should ask patients about e-cigarette use and help patients report adverse experiences by referring them to the FDA website, making relevant medical records available, or submitting a report on a patient's behalf.

The number and severity of neurological incidents reported to date is relatively small when compared to the ongoing public health emergency emerging about a mysterious lung disease in vapers. The Centers for Disease Control and Prevention (CDC) said in a September 12 statement that it had received reports of more than 480 cases of serious lung problems in the prior two months, including more than a dozen deaths linked to vaping tobacco and/or marijuana with tetrahydrocannabinol extracts, mostly in individuals under the age of 30.

The CDC issued a new case definition and classification process requiring review of medical records in all instances of such injuries and instructing all providers to specifically ask patients about e-cigarettes and/or vaping. Additional cases are expected to be reported as the classification system becomes integrated, the agency added.

Teen Usage Doubles

Barbara A. Dworetzky MD, FAAN, chief of the epilepsy program at Brigham and Women's Hospital, told Neurology Today that she has seen two patients where she was convinced that vaping had either provoked a seizure or impeded control of new-onset epilepsy until the patients curtailed the habit.

“The current reports are concerning, including those of seizure provocation, since the age group who are vaping is quite vulnerable to new-onset seizures and epilepsy,” she said. “When any physician sees a patient with a new-onset seizure, a good history requires asking about substance use of any kind, along with a toxicity screening of urine and blood.”

The extent of the problem of vaping among youth was highlighted in a release of survey data reported in the September 18 issue of TheNew England Journal of Medicine by researchers funded by the National Institute on Drug Abuse (NIDA). Data from the 2019 Monitoring the Future Survey of eighth-, tenth-, and twelfth-graders showed “alarmingly high rates” of e-cigarette use compared with just one year ago; it also showed that rates had doubled in just two years.

Earlier reports found that among middle- and high-school students, 3.62 million were current users of e-cigarettes in 2018. E-cigarette use, from 2017 to 2018, increased 78 percent among high-school students (11.7 percent to 20.8 percent) and 48 percent among middle-school students (3.3 percent to 4.9 percent). In addition, a 2013-2014 survey reported that 81 percent of youth users said the availability of appealing flavors as the primary reason for use.

Researchers at the University of Michigan in Ann Arbor reported that in 2019, more than one in four students in twelfth grade reported having vaped within the past month, as did one in five tenth graders, and one in 11 children in eighth grade.

“With 25 percent of 12th graders, 20 percent of 10th graders and 9 percent of 8th-graders now vaping nicotine within the past month, the use of these devices has become a public health crisis,” said NIDA Director Nora D. Volkow, MD.

Dr. Dworetzky, who is also a professor of neurology at Harvard Medical School, said that neurologists need to be trained to ask and screen for substance use in a nonjudgmental way in order to get honest answers about patients' use of nicotine/cannabis. She said this is critical in order to understand the cause of seizures, and whether to initiate medication, counsel patients about the dangers of various substances, and/or whether or not they need referral for help.

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“The current reports are concerning, including those of seizure provocation, since the age group who are vaping is quite vulnerable to new-onset seizures and epilepsy. When any physician sees a patient with a new-onset seizure, a good history requires asking about substance use of any kind, along with a toxicity screening of urine and blood.”—DR. BARBARA A. DWORETZKY

Figure

“It is well established that lead, arsenic, and manganese are neurotoxicants that can cause a range of problems, from headaches, drowsiness, and confusion, to seizures, as well as other life-threatening complications, depending on the dose and the persons susceptibility.”—DR. ANA MARIA RULE

“Vaping and some of the practices around it may deliver a higher/quicker dose of the substance than smoking, which could be more irritating to the brain. Also, if substances are purchased illicitly, there is the issue of unknown contaminants,” Dr. Dworetzky said.

She said that in her experience, first seizures are so frightening to patients and their loved ones that if they are asked in a nonjudgmental way focused on the best treatment it should be possible to collect such data as part of a routine evaluation, without needing expensive tools.

Toxic Metals, Higher Doses

What could be causing the reactions to vaping? In a February 18 study published in Environmental Health Perspectives—a peer-reviewed open-access journal published monthly with support from the US National Institute of Environmental Health Sciences—researchers at Johns Hopkins University analyzed concentrations in e-cigarette liquid and aerosol samples in an effort to investigate whether metals from e-cigarette heating coils were present in reservoir tanks or the aerosol generated by the coils. They found lead, chromium, nickel, manganese, and arsenic in 56 samples of e-cigarettes from daily users, and while minimal amounts were detected in refilling dispenser fluids, much larger levels were in liquids exposed to the devices' coils.

“It is well established that lead, arsenic, and manganese are neurotoxicants that can cause a range of problems, from headaches, drowsiness, and confusion, to seizures, as well as other life-threatening complications, depending on the dose and the person's susceptibility,” said Ana María Rule, PhD, an assistant professor and director of the Exposure Assessment Lab at Johns Hopkins School of Public Health, who was part of the Johns Hopkins research team.

“We found lead in 94 percent and manganese in 64 percent of aerosol samples; and half of the samples exceeded the [federal] ambient air quality standard for lead,” she told Neurology Today.

“This is a new epidemic in young children. Some of these teens have been vaping for 10 years,” she said. “I thought we would start seeing some of these effects years from now, and I'm disturbed that we are starting to see them so soon.”

As products have evolved, they have become more powerful and newer versions, notably “pods”, like those sold under the named Juul—coincidentally the first product to be backed by Altria, the first “big tobacco” company to acquire a major stake in the market. These pods deliver much higher levels of nicotine, Dr. Rule explained. “I think that we have underestimated the doses in these products, and Juul completely changed the chemistry of nicotine in e-cigarettes. One ‘pod’ contains the equivalent of smoking an entire pack of cigarettes.”

Michael D. Privitera, MD, FAAN, professor and director of the epilepsy center at the University of Cincinnati Gardner Neuroscience Institute, said that he, too, is concerned about what exactly people are vaping.

“There have been reports of various adulterated products in the vape cartridges. For decades marijuana has often been cut with other illegal drugs to create an impression of increased potency. Seizures can be an adverse effect of a variety of illegal substances, or legal substances used at high doses. Vaping generally produces high concentrations quickly, so quick increases to high concentrations of unknown additives certainly is a cause for concern.”

Prue Talbot, PhD, a professor in the department of neuroscience, molecular, cell and systems biology at the University of California, Riverside, was part of another team of investigators who published a 2018 analysis in the journal, Tobacco Control, of cytotoxicity and metal concentrations in e-cigarette fluids, aerosols, and solvents. Two years earlier, she and her colleagues systematically reviewed case reports of health problems attributed to e-cigarettes and vaping.

Dr. Rule told Neurology Today that she does not think most emergency departments ask about e-cigarettes or vaping when a patient is admitted for a seizure or other neurological crisis but hopes the barrage of recent attention will change this.

“It is probably very unlikely in the past that patients would have been asked about it. In our 2016 paper [in Preventive Medicine Reports], we suggested that medical histories contain a question on vaping. Perhaps with the medical problems currently being associated with vaping, this question will become standard in clinics and emergency departments.”

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“There have been reports of various adulterated products in the vape cartridges. For decades marijuana has often been cut with other illegal drugs to create an impression of increased potency. Seizures can be an adverse effect of a variety of illegal substances, or legal substances used at high doses. Vaping generally produces high concentrations quickly, so quick increases to high concentrations of unknown additives certainly is a cause for concern.”—DR. MICHAEL D. PRIVITERA

In an effort to curb teen use, President Trump on September 11 said the US plans to pull most vaping products from the market, and the FDA plans to ban popular fruity flavors, as well as menthol and mint e-cigarettes from stores and online sellers. The FDA is finalizing rules that were scheduled to take effect in early October. The agency said that manufacturers might be able to reintroduce products, but only after requests have been submitted and they have been formally cleared by the FDA. The current deadline for applications is in April 2020.

Link Up for More Information

• Olmedo P, Goessler W, Tanda S, et al. Metal concentrations in e-cigarette liquid and aerosol samples: The contribution of metallic coils https://ehp.niehs.nih.gov/doi/full/10.1289/EHP2175?url_ver=Z39.88-2003. Environ Health Perspect 2018;2:126(2):027010.
• Behar RZ, Wang Y, Talbot P. Comparing the cytotoxicity of electronic cigarette fluids, aerosols and solvents https://tobaccocontrol.bmj.com/content/27/3/325. Tobacco Control 2018;27(3):325–333.
• Madison MC, Landers CT, Gu BH, et al. Electronic cigarettes disrupt lung lipid homeostasis and innate immunity independent of nicotine https://www.jci.org/articles/view/128531. J Clin Invest 2019; Epub 2019 Sep 4.
    • Hua M, Talbot P. Potential health effects of electronic cigarettes: A systematic review of case reports https://www.sciencedirect.com/science/article/pii/S2211335516300523?via%3Dihub. Prev Med Rep 2016;4:169–178.