Literature Review

Is serum serotonin level associated with risk of seizure-related breathing dysfunction?



Significant increases in serum serotonin levels after seizures are associated with lower incidence of seizure-related breathing dysfunction in patients with epilepsy, according to research published online Sept. 4 in Neurology. The change in serotonin level may reflect physiologic changes that protect against harmful processes that promote sudden unexpected death in epilepsy (SUDEP), the authors wrote.

“Our results give new insight into a possible link between serotonin levels and breathing during and after seizure,” Samden D. Lhatoo, MD, professor of neurology at McGovern Medical School at the University of Texas Health Science Center in Houston, said in a press release. “This may give hope that perhaps someday new therapies could be developed that may help prevent SUDEP. However, our study was small, and much more research is needed to confirm our findings in larger groups before any treatment decisions can be made. It is also important to note that excess serotonin can be harmful, so we strongly recommend against anyone trying to find ways to increase their serotonin levels in response to our study findings.”

Animal and human studies have indicated that breathing dysfunction related to SUDEP may involve serotonergic pathways. Compared with controls, patients with SUDEP have fewer midline serotonergic neurons. Furthermore, a 2018 study suggested an association between severe seizures and decreased serotonergic tone in the postictal state.

Dr. Lhatoo and colleagues examined a prospective cohort of patients with intractable epilepsy to understand the relationship between serum serotonin levels, ictal central apnea (ICA), and postconvulsive central apnea (PCCA). Patients were aged 18 years or older, were admitted to the epilepsy monitoring unit from January 2015 to April 2018, and agreed to take part in an investigation of SUDEP biomarkers. Dr. Lhatoo and colleagues evaluated video EEG, plethysmography, capillary oxygen saturation, and ECG for 49 patients. After a patient had a clinical seizure, the researchers collected postictal and interictal venous blood samples from him or her to measure serum serotonin levels. They classified seizures using the International League Against Epilepsy 2017 seizure classification. Dr. Lhatoo and colleagues analyzed 49 seizures with and without ICA and 27 generalized convulsive seizures with and without PCCA.

Of the 49 patients, 29 were female. Participants’ mean age was 42 years, mean age at epilepsy onset was 25.2 years, and mean epilepsy duration was 16.8 years. The population’s mean body mass index was 28.9. Dr. Lhatoo and colleagues observed ICA in 17 of 49 (34.7%) seizures and PCCA in 8 of 27 (29.6%) seizures.

Postictal serum serotonin levels were significantly higher than interictal levels for seizures without ICA, but not for seizures with ICA. Among patients with generalized convulsive seizures without PCCA, serum serotonin levels were significantly increased postictally, compared with interictal levels, but not among patients with seizures with PCCA. The change in postictal and interictal serotonin levels also differed significantly between participants with and without PCCA. In patients without PCCA, an increase in serotonin was associated with an increase in heart rate, but not in patients with PCCA.

“Large postictal increases in serum serotonin may play a role in modulation of respiration in these patients,” wrote Dr. Lhatoo and colleagues. “Alternatively, the increase in serum serotonin that we measured may be a surrogate for an increase in brain serotonin levels that may depend on similar physiologic mechanisms, rather than serum serotonin directly stimulating breathing.” Low levels of postictal serum serotonin are associated with potentially harmful breathing phenomena that should be investigated in larger studies, the investigators concluded.

The study was funded by a grant from the National Institutes of Health. One author received a laboratory research grant from Zogenix.

SOURCE: Murugesan A et al. Neurology. 2019 Sep 3. doi: 10.1212/WNL.0000000000008244.

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