By: John Paisley
Defining Stroke and Risk Factors
A stroke is defined as irreversible brain tissue damage resulting from either a blood vessel blockage or rupture. There are many preventable risk factors for stroke with high blood pressure (hypertension), smoking, obesity, high blood sugar, high sodium diet, and high cholesterol (hyperlipidemia) ranking among the most common (Kleindorfer et al., 2021; Feigin et al., 2021). Additionally, certain risk factors for stroke are nonpreventable, including age, sex, race, and genetic clotting abnormalities (Boehme, Esenwa, & Elkind, 2017).
Stroke diagnoses can be divided into two major categories: ischemic and hemorrhagic. An ischemic stroke is typically what comes to people’s mind when they think of a stroke, a blockage that has formed preventing oxygen and nutrients to an area of the brain (Hui, Tadi, & Patti., 2022). Hemorrhagic stroke is commonly referred to as a brain bleed. The weakened blood vessels in the brain rupture, allowing blood to leak out. Areas of the brain become nutrient-deprived, and they are exposed to pressure differences and toxic residues resulting in cellular death (Fang et al., 2020).
Stroke is the most common cause of epilepsy diagnosis in older adults. Post-stroke epilepsy is estimated to occur in 9-12% of all adult stroke patients (Merkler et al., 2018; Conrad et al., 2013; Hardstock et al., 2021). While multiple medications are being studied; currently, there are no medications available that prevent epilepsy formation after stroke (Mishra et al., 2023).
Post-stroke seizure activity
Post-stroke seizure activity does not necessitate a diagnosis of epilepsy nor the need for long-term anti-seizure medications. Post-stroke seizure activity (PSS) is currently a large area of study. With studies having differing definitions and standards for data reporting, an international collaborative study was created in 2023 known as the International Post-Stroke Epilepsy Research Repository (IPSERR) aimed to finish research by 2028 (Mishra et al., 2023).
PSS can be subdivided into two categories early (EPSS or acute symptomatic seizures) and late (LPSS). EPSS is typically defined as seizure activity within the first 7-14 days post-stroke, depending on study parameters (Sarecka-Hujar & Kopyta, 2019; Zhao et al.,2018; Agarwal et al., 2021). EPSS is believed to be related to high levels of excitatory neurotransmitters (Glutamate) and ions shifting immediately after brain tissue injury (Armada-Moreira et al, 2020). LPSS is typically defined as seizure activity between the end of the EPSS phase and 2 years post-stroke (Zhao et al.,2018). LPSS is believed to be related to the scar formation process (Lekoubou, Fox & Ssentongo, 2020).
During the EPSS phase, seizure activity does not typically arise from a solid “epileptic network”. The chemical repercussions of a stroke are still prevalent during this time and the body can still heal (Chen et al.,2022). Thus, seizures during this phase are not typically diagnosed as epilepsy, due to the International League Against Epilepsy (ILAE) definition requiring seizure activity to be unprovoked, or without a causative event (Mauritz et al., 2022; Fisher et al., 2014). That being said, one study found a 33% chance of an unprovoked seizure reoccurrence within 10 years for seizure activity in this phase (Hesdorffer et al., 2009). It is believed that seizure activity can exacerbate damaged neurons, promote cellular death, and worsen pre-existing epilepsy; this may explain the elevated percent chance during this phase (Shen et al., 2021). In recent years, physicians have started using a post-stroke epilepsy prediction tool, SeLECT, to estimate patient risk of seizure occurrence or reoccurrence, while incorporating EPSS seizure activity its’ prediction model (Galovic et al., 2018).
In the LPSS phase, the brain attempts to heal viable damaged tissue, limit microbleeding, and promote scar tissue formation (Li et al., 2022). Scar tissue formation and the resulting altered local metabolism have been associated with epileptogenesis, development of new epileptic tissue (Boison & Steinhäuser, 2018; Sadanandan et al., 2021). This explains why one study showed a 71.5% chance of a 10-year seizure reoccurrence if an unprovoked seizure occurs in the LPSS phase (Hesdorffer et al., 2009). Seizures in the LPSS phase can be diagnosed as epilepsy. Following the 2014 ILAE definition guidelines, epilepsy may be diagnosed by one seizure if the risk for reoccurrence in 10 years is greater than 60% (Fisher et al., 2014; Freiman et al., 2023).
Post-stroke goals and care
Rehabilitation and stroke prevention are two goals during post-stroke care. Stroke rehabilitation strategies are customized by healthcare professionals, taking into account the stroke’s location and its effects on different body areas. Speech therapy, physical therapy, and occupational therapy may be consulted to assist patients with navigating their activities of daily life.
Speech therapy: focuses on speaking and swallowing difficulties.
Physical therapy: focuses on relearning large-scale movements such as walking, sitting, and stability.
Occupational therapy: focuses on skills necessary for independent living and care such as eating, drinking, and dressing.
Stroke prevention is based on preventing reoccurrence and controlling stroke risk factors. Depending on which risk factors a patient presents with, will determine what medications and lifestyle changes will be prescribed. This can include but is not limited to antihypertensive medications, cholesterol-lowering medications, diabetic medication adjustments, smoking cessation, dietary changes, exercise, and antiplatelet or anticoagulant medications (Kleindorfer et al., 2021). Except for a few exceptions, almost all patients will be placed on either Warfarin, an antiplatelet, or a direct oral anticoagulant (DOAC) (Kleindorfer et al., 2021). These medications reduce the risk for blood clot formation with the most common side effect being easier bruising.
Medication changes and considerations
Patients with epilepsy who present to the hospital with a stroke may have their seizure medications altered during their admission. Many antiseizure medications have been associated with increased cholesterol levels and atherosclerosis formation, which increases stroke risk (Chuang et al., 2012; Lopinto-Khoury, & Mintzer, 2010; Josephson et al., 2021). Antiseizure medications that act on enzymatic activity have been associated with DOAC failure, and increased Warfarin metabolism (Goldestein et al., 2023; Larsson et al., 2021). This may warrant dosage adjustments at follow-up appointments; however, abrupt cessation of enzymatic-acting antiseizure medications can result in an abnormally high risk for bleeding. It is recommended that you discuss this with your prescribing physician prior to cessation of the medication.
Resources:
Agarwal, A., Sharma, J., Padma Srivastava, M. V., Bhatia, R., Singh, M. B., Gupta, A., Pandit, A. K., Singh, R., Rajan, R., Dwivedi, S., Upadhyay, A., Garg, A., & Vishnu, V. Y. (2021). Early Post-Stroke Seizures in Acute Ischemic Stroke: A Prospective Cohort Study. Annals of Indian Academy of Neurology, 24(4), 580–585. https://doi.org/10.4103/aian.AIAN_1283_20
Armada-Moreira, A., Gomes, J. I., Pina, C. C., Savchak, O. K., Gonçalves-Ribeiro, J., Rei, N., Pinto, S., Morais, T. P., Martins, R. S., Ribeiro, F. F., Sebastião, A. M., Crunelli, V., & Vaz, S. H. (2020). Going the Extra (Synaptic) Mile: Excitotoxicity as the Road Toward Neurodegenerative Diseases. https://www.frontiersin.org/articles/10.3389/fncel.2020.00090/full#B245
Boehme, A. K., Esenwa, C., & Elkind, M. S. (2017). Stroke Risk Factors, Genetics, and Prevention. Circulation research. https://doi.org/10.1161/CIRCRESAHA.116.308398
Boison, D., & Steinhäuser, C. (2018). Epilepsy and astrocyte energy metabolism. Glia. https://doi.org/10.1002/glia.23247
Chen, J., Ye, H., Zhang, J., Li, A., & Ni, Y. (2022). Pathogenesis of seizures and epilepsy after stroke. Acta Epileptologica. https://aepi.biomedcentral.com/articles/10.1186/s42494-021-00068-8#:~:text=In%20later%20stages%20of%20stroke,and%20leading%20to%20late%20epilepsy.
Chuang, Y. C., Chuang, H. Y., Lin, T. K., Chang, C. C., Lu, C. H., Chang, W. N., Chen, S. D., Tan, T. Y., Huang, C. R., & Chan, S. H. (2012). Effects of long-term antiepileptic drug monotherapy on vascular risk factors and atherosclerosis. Epilepsia. https://doi.org/10.1111/j.1528-1167.2011.03316.x
Conrad, J., Pawlowski, M., Dogan, M., Kovac, S., Ritter, M. A., & Evers, S. (2013). Seizures after cerebrovascular events: risk factors and clinical features. Seizure. https://doi.org/10.1016/j.seizure.2013.01.014
Fang, Y., Gao, S., Wang, X., Cao, Y., Lu, J., Chen, S., Lenahan, C., Zhang, J., Shao, A., & Zhang, J. (2020). The Frontiers. Programmed Cell Deaths and Potential Crosstalk With Blood–Brain Barrier Dysfunction After Hemorrhagic Stroke .https://doi.org/10.3389/fncel.2020.00068
Feigin, V., Stark, B., Johnson, C., Roth, G., Bisignano, C., Abady, G., et al. (2021). Global, regional, and national burden of stroke and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. The Lancet: Neurology. https://doi.org/10.1016/S1474-4422(21)00252-0
Freiman, S., Hauser, W. A., Rider, F., Yaroslavskaya, S., Sazina, O., Vladimirova, E., Kaimovsky, I., Shpak, A., Gulyaeva, N., & Guekht, A. (2023). Post-stroke seizures, epilepsy, and mortality in a prospective hospital-based study. Frontiers in neurology. https://doi.org/10.3389/fneur.2023.1273270
Galovic, M., Döhler, N., Erdélyi-Canavese, B., Felbecker, A., Siebel, P., Conrad, J., et al. (2018). Prediction of late seizures after ischaemic stroke with a novel prognostic model (the SeLECT score): a multivariable prediction model development and validation study. The Lancet: Neurology. https://doi.org/10.1016/S1474-4422(17)30404-0
Goldstein, R., Jacobs, A. R., Zighan, L., Gronich, N., Bialer, M., & Muszkat, M. (2023). Interactions Between Direct Oral Anticoagulants (DOACs) and Antiseizure Medications: Potential Implications on DOAC Treatment. CNS drugs. https://doi.org/10.1007/s40263-023-00990-0
Hesdorffer, D., Benn, E., Cascino, G., & Hauser, A. 2009. Is a first acute symptomatic seizure epilepsy? Mortality and risk for recurrent seizure. Epilepsia. https://doi.org/10.1111/j.1528-1167.2008.01945.x
Hui C, Tadi P, Patti L. (2022). Ischemic Stroke. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK499997/
Ibrahim F, Murr N. (2022). Embolic Stroke. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK564351/
Josephson CB, Wiebe S, Delgado-Garcia G, et al. (2021). Association of Enzyme-Inducing Antiseizure Drug Use With Long-term Cardiovascular Disease. JAMA Neurol. https://doi.org/10.1001/jamaneurol.2021.3424
Larsson D, Baftiu A, Johannessen Landmark C, et al. (2021). Association Between Antiseizure Drug Monotherapy and Mortality for Patients With Poststroke Epilepsy. JAMA Neurol. https://doi.org/10.1001/jamaneurol.2021.4584
Kleindorfer, D., Towfighi, A., Chaturvedi, S., Cockroft, K., Gutierrez, J., Lombardi-Hill, D., Kamel, H., Kernan, W., Kittner, S., Leira, E., et al. (2021). 2021 guideline for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline from the American Heart Association/American Stroke Association. American Heart Association: Stroke. https://doi.org/10.1161/STR.0000000000000375
Li, L., Zhou, J., Han, L., Wu, X., Shi, Y., Cui, W., Zhang, S., Hu, Q., Wang, J., Bai, H., Liu, H., Guo, W., Feng, D., & Qu, Y. (2022). The Specific Role of Reactive Astrocytes in Stroke. Frontiers in cellular neuroscience. https://doi.org/10.3389/fncel.2022.850866
Lopinto-Khoury, C., & Mintzer, S. (2010). Antiepileptic drugs and markers of vascular risk. Current treatment options in neurology. https://doi.org/10.1007/s11940-010-0080-y
Mauritz, M., Lawrence, J., Camfield, P., Chin, R., Nardone, R., Lattanzi, S., & Trinka, E. (2022). Acute symptomatic seizures: an educational, evidence-based review. Epileptic Disorders. https://doi.org/10.1684/epd.2021.1376
Merkler, A. E., Gialdini, G., Lerario, M. P., Parikh, N. S., Morris, N. A., Kummer, B., Dunn, L., Reznik, M. E., Murthy, S. B., Navi, B. B., Grinspan, Z. M., Iadecola, C., & Kamel, H. (2018). Population-Based Assessment of the Long-Term Risk of Seizures in Survivors of Stroke. Stroke. https://doi.org/10.1161/STROKEAHA.117.020178
Mishra, N. K., Kwan, P., Tanaka, T., Sunnerhagen, K. S., Dawson, J., Zhao, Y., Misra, S., Wang, S., Sharma, V. K., Mazumder, R., Funaro, M. C., Ihara, M., Nicolo, J. P., Liebeskind, D. S., Yasuda, C. L., Cendes, F., Quinn, T. J., Ge, Z., Scalzo, F., Zelano, J., et al. International Post Stroke Epilepsy Research Consortium (IPSERC) (2023). Clinical characteristics and outcomes of patients with post-stroke epilepsy: protocol for an individual patient data meta-analysis from the International Post-stroke Epilepsy Research Repository (IPSERR). BMJ open. https://doi.org/10.1136/bmjopen-2023-078684
Sadanandan, N., Saft, M., Gonzales-Portillo, B., & Borlongan, C. (2021). Multipronged Attack of Stem Cell Therapy in Treating the Neurological and Neuropsychiatric Symptoms of Epilepsy. Frontiers. https://doi.org/10.3389/fphar.2021.596287
Sarecka-Hujar, B., & Kopyta, I. (2019). Poststroke epilepsy: current perspectives on diagnosis and treatment. Neuropsychiatric disease and treatment, 15, 95–103. https://doi.org/10.2147/NDT.S169579
Shen, Y., Gong, Y., Ruan, R., Chen, Z., & Xu, C. (2021). Secondary Epileptogenesis: Common to See, but Possible to Treat? Frontiers | Secondary Epileptogenesis: Common to See, but Possible to Treat? (frontiersin.org)
Yin, Y., Zhang, L., Marshall, I., Wolfe, C., & Wang, Y. (2022). Statin Therapy for Preventing Recurrent Stroke in Patients with Ischemic Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials and Observational Cohort Studies. Neuroepidemiology. https://doi.org/10.1159/000525672
Zhao, Y., Li, X., Zhang, K., Tong, T., & Cui, R. (2018). The Progress of Epilepsy after Stroke. Current neuropharmacology. https://doi.org/10.2174/1570159X15666170613083253
