Warren Boling, MD, FAANS, FRCSC, FRACS
Chair, Department of Neurosurgery at Loma Linda University. Dr. Boling is service director for the International Consortium for the treatment of Epilepsy in Under-served Settings, as well as director of CURE Children’s Hospital of Uganda of the Comprehensive Epilepsy Program. His specialty includes Epilepsy Surgery.
Epilepsy is an important public health problem representing 0.6% of the global burden of disease [Murray, et al. Lancet 2012] that particularly impacts the people living in low income and rural settings. The prevalence of epilepsy is about 1.2% in North America [https://www.cdc.gov/epilepsy/data/index.html], and cross the Asian continent, median prevalence has been observed to be similar to that found in Europe and North America, although significant prevalence differences are present in rural and urban dwellers. In Southern provinces of China, a door-to-door survey identified the prevalence of epilepsy to be significantly higher in rural areas [Pi, et al. Eur J Epielpsy 2014]. Wang, et al. also identified a contrast in epilepsy prevalence between rural and urban provinces with higher epilepsy rates in more rural provinces of Heilongjiang and Ningxia and relatively less epilepsy in the more urban province of Henan [Wang, et al. Bull WHO 2018]. Likewise, in Pakistan and India twice the epilepsy prevalence has been identified in rural compared with urban areas (6.23 versus 3.04 per 1000) [Mac, et al. Lancet Neurol 2007, Rajshekhar, et al. Neurology 2006]. A higher rural epilepsy prevalence most likely results from factors contributing to an epilepsy treatment gap worldwide such as lower socioeconomic status of rural dwelling people and less access to medical clinics, health care providers, and medications. Additional possible factors impacting higher rates of epilepsy in rural areas include exposure to environmental etiologies of epilepsy such as parasites and less knowledge in rural areas of medical treatment options and greater reliance on traditional healers.
The treatment gap in epilepsy can be defined as the proportion of people with epilepsy who require treatment but do not receive it, and this parameter has been proposed as a useful concept to compare quality of care of epilepsy patients across regions and countries. Treatment gap is strongly influenced by socioeconomics of a region or country.
In Yueyang County, Hunan province, a more rural region of China, a door-to-door survey of epilepsy [Pi, et al. Epilepsy Res 2012 ] found 35.0% of people with epilepsy (PWE) had never been diagnosed or treated, 57.3% of PWE received non-standard treatments, and only 7.7% of patients received standard treatment. Non-standard treatments included the use of Chinese medicine in 42.7%. Questionnaire-based interviews conducted in rural Western China to identify active convulsive epilepsy found estimated prevalence was 1.8 per 1000 in this population with a treatment gap estimated to be 66.3% [Hu, et al. Eur J Epilepsy 2014]. The authors identified that a majority of individuals with epilepsy had consulted a doctor but failed to receive or adhere to an appropriate treatment program. Common themes that contribute to a gap in treatment include poverty, lack of access to medications, inadequate access to epilepsy trained physicians, poor knowledge about epilepsy among the community and healthcare providers, failed models of healthcare delivery, as well epilepsy associated stigma.
Stigma and Psychosocial Impact of Epilepsy
The psychosocial consequences of epilepsy can be profound due to epilepsy related stigma leading to low self-esteem and marginalization in society. In Asia, a misconception that epilepsy is hereditary is a common belief, which may result in an inability to marry for the PWE and negative impact on the family of PWE [Snape, et al. Epilepsy Behav 2009]. The psychological burden of epilepsy in China was assessed by asking PWE the question “What do you worry about most” [Wang, et al. Epilepsy Behav 2009]. Eighty percent of responders replied: ‘‘when the next seizure might occur” and the second most frequent response was: ‘‘facing discrimination”. In rural areas, traditional beliefs more commonly shape the definitions and treatment of epilepsy, which results in patients and families seeking less Western medical treatment. Negative attitudes towards PWE are mostly encountered in rural China [Wang et al. Bull WHO 2008] where about half of the population surveyed believed that PWE should not be employed and identified epilepsy as a mental disorder equivalent to insanity. Even among more educated individuals and community leaders, about half perceived epilepsy as a ‘terrible’ condition, that the disease was not curable, and may be hereditary [Yang, et al. Epilepsy Behav 2011]. High rates of stigma have been reported by Chinese PWE and their families. In a survey of PWE in China, about 30% of PWE thought they were treated differently by others because of their epilepsy and 50% chose to keep their epilepsy secret [Li, et al. Epilepsy Behav 2010]. In both China and Vietnam, surveys of attitudes about PWE have found widespread attitudes of epilepsy that prevents or hinders school attendance, employment, and marriage [Jacoby, et al. Epilepsy Behav 2008].
Medically Intractable Epilepsy
About 30% of PWE will have ongoing recurrent seizures despite medical treatment, so-called intractable epilepsy. Intractable epilepsy has now been defined by the International League Against Epilepsy (ILAE) as recurring seizures that continue unabated despite trying and failing at least 2 anticonvulsant medications over at least one year [Kwan, et al. Epilepsia 2010]. Despite many new anticonvulsant medications available today, the new medications are no more efficacious in controlling seizures although with potential for improved side effect profiles. Intractable epilepsy is dangerous and life-threatening significantly elevating mortality rates of PWE to 4.69 times that of individuals without epilepsy [Sperling, et al. Ann Neurol 1999]. However, the excess morbidity and mortality of epilepsy is eliminated with seizure control. And intervention to treat medically intractable epilepsy with surgery to stop the seizures dramatically reduces mortality to the same as the general population.
Surgery of Epilepsy
Medically intractable epilepsy is a chronic, disabling and dangerous disease. However, surgery will stop seizures in the majority of well-selected individuals, eliminating the elevated mortality and morbidity associated with intractable recurring seizures. Additionally, surgical treatment of drug-resistant epilepsy improves QOL and reduces stigma (Fletcher, et al. Epilepsy Behav. 2015). The benefits realized by stopping seizures underpin an emphasis to surgically treat intractable epilepsy when a clear opportunity for seizure freedom exists. Surgery is the only opportunity to cure intractable epilepsy, and, therefore, should be considered as an important treatment approach in high and low resource regions of the world to eliminate excess mortality of intractable epilepsy and mitigate the psychosocial consequences that impact individuals with medically intractable epilepsy.
Many advances in the surgical treatment of epilepsy have been made recently largely driven by greater computing capabilities and improvements in brain imaging. One example is laser thermal ablation. Use of the fiber optic laser as the thermal source of ablation has been a great advance compared to the earlier radiofrequency ablation technique. Since the fiberoptic line that transmits the laser light is non-ferromagnetic, the ablation procedure can be performed in the MRI magnet, which also takes advantage of a major advancement in MR imaging that allows temperature gradients to be measured during MR imaging. Thermography measures imaging variables that have good linear correlation with temperature. The excellent linearity and temperature dependence of the proton resonance frequency (PRF) in relation to most all tissue types have made PRF-based phase mapping methods the preferred choice for thermal mapping and this acquisition protocol is available on most all modern MRI units. The thermal map is then fused with the anatomical image during a thermal ablation treatment so that the ablation can be monitored near real-time to confirm the ablation encompassed the epilepsy focus and did not encroach on critical brain structures.
Laser ablation treatment has now-a-days become the preferred treatment approach for small areas of focal cortical dysplasia and other neuronal migration abnormalities that commonly are the cause of severe intractable epilepsy. (Figure 1)
Figure 1. 15 year old girl with frequent and medically intractable seizures who was found to have multiple bilateral subependymal nodular heterotopias. Intracranial electrode monitoring from the nodular heterotopias identified seizure onsets confined to the left occipital heterotopia (see arrow). Her visual fields were normal. To provide the best opportunity of preserving the patient’s visual fields and also treat her intractable seizures, laser ablation treatment was performed of the epilepsy focus heterotopia.
Figure 2. A Monteris Medical (Winnipeg, Canada) laser probe was inserted to the heterotopia target and heated to a temperature sufficient to ablate the malformation. Contrast enhancement indicates the epileptic tissue was destroyed (2.a. axial T1 post contrast and 2.b. sagittal T1 post contrast). After surgery the patient has been seizure free.