THE TEAM
Group 9: Amy Kan (2519603), Laura Copland (2545117), Sofia Miscio (2539413), Timothy Girgis(2614615), Haohua Liu (2576490)
UNDERSTANDING HUMAN EPILEPSY
Epilepsy is a serious disorders of the central nervous system, defined as two unprovoked seizures occurring >24 hours apart (Thijs et al., 2019). It is the second most common chronic neurological condition seen by neurologists, affecting ~50 million people worldwide, nearly 80% of whom come from low or middle-income countries (Saxena and Li, 2017). A meta-analysis by Fiest et al. (2017) found an overall lifetime prevalence of 7.60 per 1000, a figure which was higher in low and middle-income countries (8.75 per 1000). Compared with the general population, mortality risk is 2-4 times higher for epileptics, and is highest in the first 10 years after diagnosis (Sridharan, 2002).
Given the significant early mortality, early recognition is the key to timely diagnosis and the treatment needed to avoid adverse outcomes
University of Glasgow BIOL 2C Human Biology
Mr. Nairn Scobie Glasgow, Scotland February 17, 2022
BIOLOGICAL MECHANISMS
Diagnosis of epilepsy can happen as early as after 2 seizures, and on rare occasions 1 if there is reason to believe another is imminent. Seizures refer to abnormal brain activity, due to a “neurological assault” whereby brain cells (neural cells) are overactive and cause the body to involuntarily convulse and shake. Seizures often last seconds and sometimes minutes. Resting potentials are extremely important given how seizures occur. Resting potential is the charge inside a cell when there is an electrical imbalance between the inside of the cell and the outside (Scharfman, 2007). Resting potential in cells is set normally to ensure that neurons can discharge appropriately (so that the brain is not constantly firing neurons) while remaining high enough to allow release when needed. A seizure occurs when the difference in voltage is unbalanced, and an assault of neurons are fired from the brain.
PROPOSED FUTURE RESEARCH
As >30% of patients receiving antiepileptics still experience seizures, research has trended toward curing the underlying causes of epilepsy (Jacobs et al., 2001). This trend should aim to examine the potential for personalized medicine, in which the genetic subsets that do not respond to current medication are identified and better targetted with specialized medication that are likely to be more effective than the “one-size-fits-all” approach (Jacobs et al., 2001). Further research on the risks and benefits of invasive surgery (which involves removing the part of the brain that causes seizures) may also be warranted in light of the recently confirmed efficacy of some surgerical interventions for patients that do not respond to antiepileptics.
RISK FACTORS
In regard to demographic risk factors, epilepsy effects both sexes and all ages, but prevalence and incidence are slightly higher in men and older age groups due to a higher frequency of strokes, neurodegenerative diseases, and tumors. Incidence is also higher in low-income countries due to higher rates of Central Nervous System infections (Beghi, 2020). Environmental factors also contribute to the risk of epilepsy. Cansu et al. (2007) observed a strong correlation between the presence of neurological abnormalities and epilepsy, and found that children experiencing head injuries were more likely to develop epilepsy, as well as children whose mother developed hypertension before or during pregnancy.
Genetics are also a significant risk factor. Singh et al. (1998) found that a KCNQ2 gene mutation caused reduced control of potassium channels. Voltage-gated channels act as “gateways” that open to allow an influx of sodium or calcium into the cell (”depolarization”) until a threshold is reached, and the potassium channels then open for potassium to exit the cell (”repolarisation”), as illustrated in Figure 1. In individuals with the KCNQ2 mutation, these potassium channels remain open longer, leading to epileptic seizures.
TREATMENT OPTIONS
Antiseizure medication is the primary treatment for epilepsy (Thijs et al., 2019), despite an efficacy of only 66% and limited availability outside of high-income countries (Duncan et al., 2006). Doses are built up gradually and additional drugs can be introduced if necessary (Thijs et al., 2019). If medication is not effective, other treatments can be considered, including surgery, electrical nerve stimulation, and dietary changes (Thijs et al., 2019). Some patients with drug-resistant epilepsy can benefit from surgical removal or disconnection of small regions of the brain, which can be effective in 50-80% of those who are elgible (Ryvlin et al., 2014).
Figure 1. Potassium channel (blue proteins) and voltage-gated channel (green proteins ). Left image shows an open voltage -gated channel (depolarization), right shows open potassium channel (repolarization).
WORKS CITED
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