- Email: [email protected]
Surgery for epilepsy: the need for global acceptance and access
Comment
Meanwhile, we must remain cautious in interpreting the significance of any single pathology as unique to blast-associated TBI based on a small and heterogeneous case series and little clinical information, and few control comparisons. The alternative is to risk repeating the errors of the past decade and to consider valid the premature assumption that chronic traumatic encephalopathy is a unique disease of athletes, or even exclusively tau-associated.
1 2 3
4 5
6
*William Stewart, Douglas H Smith Penn Center for Brain Injury and Repair and Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, USA (WS, DHS); Department of Neuropathology, Queen Elizabeth University Hospital, Glasgow G51 4TF, UK (WS); and Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, UK (WS) Department of Neuropathology, Queen Elizabeth University Hospital, Glasgow G51 4TF, UK [email protected] WS and DHS are supported by NIH grant NS038104 and DOD grant PT110785; DHS is supported by NIH grants NS092389 and NS056202; and WS is supported by an NHS Research Scotland Career Researcher Fellowship.
7
8
9
10
Masel BE, DeWitt DS. Traumatic brain injury: a disease process, not an event. J Neurotrauma 2010; 27: 1529–40. Smith DH, Johnson VE, Stewart W. Chronic neuropathologies of single and repetitive TBI: substrates of dementia? Nat Rev Neurol 2013; 9: 211–21. US Department of Defense. US Department of Defense. Special Report: Traumatic brain injury. http://archive.defense.gov/home/ features/2015/0315_tbi/ (last accessed April 19, 2016). Rosenfield JV, McFarlane, AC, Bragge, P, Armondo RA, Grimes JB, Ling GS. Blast-related traumatic brain injury. Lancet Neurol 2013; 12: 882–93. US Army Medical Research and Materiel Command. Congressionally Directed Medical Research Programs. Annual Report. September 30, 2015. http://cdmrp.army.mil/pubs/annreports/2015annrep/2015annreport.pdf (accessed April 18, 2016). Shively SB, Horkayne-Szakaly I, Jones RV, Kelly JP, Armstrong RC, Perl DP. Characterisation of interface astroglial scarring in the human brain after blast exposure: a post-mortem case series. Lancet Neurol 2016; published online June 9. http://dx.doi.org/10.1016/S1474-4422(16)30057-6. Omalu B, Hammers JL, Bailes J, Hamilton RL, Kamboh MI, Webster G, Fitzsimmons RP. Chronic traumatic encephalopathy in an Iraqi war veteran with posttraumatic stress disorder who committed suicide. Neurosurg Focus 2011; 31: E3 Goldstein LE, Fisher AM, Tagge CA, et al. Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model. Sci Transl Med 2012; 4: 134ra60 Ryu J, Horkayne-Szakaly I, et al. The problem of axonal injury in the brains of veterans with histories of blast exposure. Acta Neuropathol Comm 2014; 2: 153 Helmick KM, Spells CA, Malik SZ, Davies CA, Marion DW, Hinds SR. Traumatic brain injury in the US military: epidemiology and key clinical and research programs. Brain Imaging Behav 2015; 9: 358–66.
Surgery for epilepsy: the need for global acceptance and access See Personal View page 982
For the prevelence of epilepsy in the USA see http://www.cdc. gov/epilepsy/basics/fast-facts. htm
898
Despite roughly a third of patients with epilepsy being refractory to antiepileptic drug therapy and many recent technical advances in neurosurgery, epilepsy surgery remains largely underused. In The Lancet Neurology Nathalie Jetté and colleagues1 have made a compelling case as to why this occurs in high-income countries, thoughtfully addressing many constraining barriers, including the misconceptions of physicians and the public, that prevent timely referral to an epilepsy centre for surgical assessment. Although the authors mainly focused their Personal View on high-income countries, they rightfully emphasised the substantial epilepsy treatment gap in low-income and middle-income countries, citing evidence that more than 75% of affected individuals in these countries might have no access to any sort of treatment. This problem is heightened when considering that epilepsy might be considerably more prevalent in some of these countries than in high-income countries. For instance, the prevalence of epilepsy in east Africa has been estimated to be as high as 20 per 1000 population, compared with 1% in adults and 0·6% in children in the USA.2 This
prevalence might partly relate to childhood cerebral malaria, which increases the risk of persistent epilepsy among survivors.3 An additional factor might be the high regional incidence of purulent ventriculitis and cerebritis in newborn babies, resulting in long-term neurological sequelae.4,5 For a country such as Uganda with a population of roughly 30 million, 600 000 (2%) people are expected to be affected by epilepsy, of whom 180 000 (30%) are likely to be refractory to medical treatment even if it were readily available.6 Of patients with intractable epilepsy, children in particular benefit greatly from the elimination or reduction of both seizures and antiepileptic drug treatment early in life. In addition to the sheer scale of the problem, the plight of individuals with epilepsy in low-income and middleincome countries is worsened by several factors. Jetté and colleagues have pointed out the severe shortage of neurologists and EEG and imaging capabilities in these countries. Thus, even basic diagnosis is often unavailable, and the availability of antiepileptic drugs (eg, phenytoin, phenobarbital, carbamazepine, and valproate) might also be limited,7 particularly where economic barriers exist. In some communities, people www.thelancet.com/neurology Vol 15 August 2016
Comment
with epilepsy are more severely stigmatised than those in high-income countries; thus, health-care access and societal and government support systems are often inadequate, and opportunities for education, work, and marriage can be severely limited. Even when seizures are relatively well controlled with medical management, the stigma associated with having epilepsy often remains. A high prevalence of epilepsy, increased stigmatisation, and inadequate access to effective medical therapy, make a compelling argument for the provision of epilepsy surgery in low-income and middleincome countries. Although such an argument might seem irrational in the face of other problems such as poverty, inadequate infrastructure, and restricted access to basic health care, it is feasible that epilepsy surgery can be increased in low-income and middle-income countries with minimal resources. For example, regional health centres can be developed to facilitate surgery using available resources, information technology, and collaborative partnerships with external consultants, as has been piloted by Boling and colleagues7 at CURE Children’s Hospital of Uganda (CCHU). In this model, patients were pre-screened with questionnaires at regional health clinics to determine those who were most likely to have medically refractory temporal lobe epilepsy. Candidates had cranial CT (as MRI was not available) and digital video-EEG monitoring at the CCHU. All data were sent electronically to, and reviewed by, partnering epileptologists in the USA for surgical candidate selection. A visiting neurosurgeon from the USA also trained an Ugandan neurosurgeon at the CCHU to perform a standard corticoamygdalohippocampectomy. Of 49 patients initially screened, ten met the criteria and had the operation. Six of the ten patients had complete seizure freedom, and eight had a more than 90% reduction in seizure frequency with no operative mortality and minimal morbidity (one wound infection). Of course, external funding and volunteer efforts supported this programme, and, as with any
www.thelancet.com/neurology Vol 15 August 2016
medical intervention in low-income and middle-income countries, the use of scarce health-care funding to make this sustainable should be challenged. However, Jetté and colleagues1 cite persuasive evidence that epilepsy surgery is extremely cost-effective and is associated with substantial savings in health-care expenditures over time compared with medical treatment. The enormous societal and individual costs of untreated epilepsy in all countries calls for a solution. The fact that this is only one of many daunting problems in developing countries should not diminish its importance. This is a life-threatening, profoundly disabling, and yet potentially curable condition. Making epilepsy surgery a widely accepted and accessible treatment option for all appropriate candidates, rather than a therapy of last resort or an unattainable luxury, will require the education of practitioners and the public alike, as well as innovation and investment to make it more accessible worldwide, but this can and should be done. Benjamin Warf Department of Neurosurgery, Harvard Medical School and Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115, USA [email protected] I declare no competing interests. 1
2
3 4
5
6 7
Jetté N, Sander JW, Keezer MR. Surgical treatment for epilepsy: the potential gap between evidence and practice. Lancet Neurol 2016; 15: 982–94. Rwiza HT, Kilonzo GP, Haule J, et al. Prevalence and incidence of epilepsy in Ulanga, a rural Tanzanian district: a community-based study. Epilepsia 1992; 33: 1051–56. WHO. Severe malaria. Trop Med Int Health 2014; 19 (suppl S1): 7–131. Warf BC. Hydrocephalus in Uganda: predominance of infectious origin and primary management with endoscopic third ventriculostomy. J Neurosurg 2005; 102: 1–15. Warf BC, Dagi AR, Nsbuga B, Schiff SJ. Five year survival and outcome of treatment for post-infectious hydrocephalus in Ugandan infants. J Neurosurg Pediatr 2011; 8: 502–08. Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med 2000; 342: 314–19. Boling W, Palade A, Wabulya A, et al. Surgery for pharmacoresistant epilepsy in the developing world: a pilot study. Epilepsia 2009; 50: 1256–61.
899
Meanwhile, we must remain cautious in interpreting the significance of any single pathology as unique to blast-associated TBI based on a small and heterogeneous case series and little clinical information, and few control comparisons. The alternative is to risk repeating the errors of the past decade and to consider valid the premature assumption that chronic traumatic encephalopathy is a unique disease of athletes, or even exclusively tau-associated.
1 2 3
4 5
6
*William Stewart, Douglas H Smith Penn Center for Brain Injury and Repair and Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, USA (WS, DHS); Department of Neuropathology, Queen Elizabeth University Hospital, Glasgow G51 4TF, UK (WS); and Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, UK (WS) Department of Neuropathology, Queen Elizabeth University Hospital, Glasgow G51 4TF, UK [email protected] WS and DHS are supported by NIH grant NS038104 and DOD grant PT110785; DHS is supported by NIH grants NS092389 and NS056202; and WS is supported by an NHS Research Scotland Career Researcher Fellowship.
7
8
9
10
Masel BE, DeWitt DS. Traumatic brain injury: a disease process, not an event. J Neurotrauma 2010; 27: 1529–40. Smith DH, Johnson VE, Stewart W. Chronic neuropathologies of single and repetitive TBI: substrates of dementia? Nat Rev Neurol 2013; 9: 211–21. US Department of Defense. US Department of Defense. Special Report: Traumatic brain injury. http://archive.defense.gov/home/ features/2015/0315_tbi/ (last accessed April 19, 2016). Rosenfield JV, McFarlane, AC, Bragge, P, Armondo RA, Grimes JB, Ling GS. Blast-related traumatic brain injury. Lancet Neurol 2013; 12: 882–93. US Army Medical Research and Materiel Command. Congressionally Directed Medical Research Programs. Annual Report. September 30, 2015. http://cdmrp.army.mil/pubs/annreports/2015annrep/2015annreport.pdf (accessed April 18, 2016). Shively SB, Horkayne-Szakaly I, Jones RV, Kelly JP, Armstrong RC, Perl DP. Characterisation of interface astroglial scarring in the human brain after blast exposure: a post-mortem case series. Lancet Neurol 2016; published online June 9. http://dx.doi.org/10.1016/S1474-4422(16)30057-6. Omalu B, Hammers JL, Bailes J, Hamilton RL, Kamboh MI, Webster G, Fitzsimmons RP. Chronic traumatic encephalopathy in an Iraqi war veteran with posttraumatic stress disorder who committed suicide. Neurosurg Focus 2011; 31: E3 Goldstein LE, Fisher AM, Tagge CA, et al. Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model. Sci Transl Med 2012; 4: 134ra60 Ryu J, Horkayne-Szakaly I, et al. The problem of axonal injury in the brains of veterans with histories of blast exposure. Acta Neuropathol Comm 2014; 2: 153 Helmick KM, Spells CA, Malik SZ, Davies CA, Marion DW, Hinds SR. Traumatic brain injury in the US military: epidemiology and key clinical and research programs. Brain Imaging Behav 2015; 9: 358–66.
Surgery for epilepsy: the need for global acceptance and access See Personal View page 982
For the prevelence of epilepsy in the USA see http://www.cdc. gov/epilepsy/basics/fast-facts. htm
898
Despite roughly a third of patients with epilepsy being refractory to antiepileptic drug therapy and many recent technical advances in neurosurgery, epilepsy surgery remains largely underused. In The Lancet Neurology Nathalie Jetté and colleagues1 have made a compelling case as to why this occurs in high-income countries, thoughtfully addressing many constraining barriers, including the misconceptions of physicians and the public, that prevent timely referral to an epilepsy centre for surgical assessment. Although the authors mainly focused their Personal View on high-income countries, they rightfully emphasised the substantial epilepsy treatment gap in low-income and middle-income countries, citing evidence that more than 75% of affected individuals in these countries might have no access to any sort of treatment. This problem is heightened when considering that epilepsy might be considerably more prevalent in some of these countries than in high-income countries. For instance, the prevalence of epilepsy in east Africa has been estimated to be as high as 20 per 1000 population, compared with 1% in adults and 0·6% in children in the USA.2 This
prevalence might partly relate to childhood cerebral malaria, which increases the risk of persistent epilepsy among survivors.3 An additional factor might be the high regional incidence of purulent ventriculitis and cerebritis in newborn babies, resulting in long-term neurological sequelae.4,5 For a country such as Uganda with a population of roughly 30 million, 600 000 (2%) people are expected to be affected by epilepsy, of whom 180 000 (30%) are likely to be refractory to medical treatment even if it were readily available.6 Of patients with intractable epilepsy, children in particular benefit greatly from the elimination or reduction of both seizures and antiepileptic drug treatment early in life. In addition to the sheer scale of the problem, the plight of individuals with epilepsy in low-income and middleincome countries is worsened by several factors. Jetté and colleagues have pointed out the severe shortage of neurologists and EEG and imaging capabilities in these countries. Thus, even basic diagnosis is often unavailable, and the availability of antiepileptic drugs (eg, phenytoin, phenobarbital, carbamazepine, and valproate) might also be limited,7 particularly where economic barriers exist. In some communities, people www.thelancet.com/neurology Vol 15 August 2016
Comment
with epilepsy are more severely stigmatised than those in high-income countries; thus, health-care access and societal and government support systems are often inadequate, and opportunities for education, work, and marriage can be severely limited. Even when seizures are relatively well controlled with medical management, the stigma associated with having epilepsy often remains. A high prevalence of epilepsy, increased stigmatisation, and inadequate access to effective medical therapy, make a compelling argument for the provision of epilepsy surgery in low-income and middleincome countries. Although such an argument might seem irrational in the face of other problems such as poverty, inadequate infrastructure, and restricted access to basic health care, it is feasible that epilepsy surgery can be increased in low-income and middle-income countries with minimal resources. For example, regional health centres can be developed to facilitate surgery using available resources, information technology, and collaborative partnerships with external consultants, as has been piloted by Boling and colleagues7 at CURE Children’s Hospital of Uganda (CCHU). In this model, patients were pre-screened with questionnaires at regional health clinics to determine those who were most likely to have medically refractory temporal lobe epilepsy. Candidates had cranial CT (as MRI was not available) and digital video-EEG monitoring at the CCHU. All data were sent electronically to, and reviewed by, partnering epileptologists in the USA for surgical candidate selection. A visiting neurosurgeon from the USA also trained an Ugandan neurosurgeon at the CCHU to perform a standard corticoamygdalohippocampectomy. Of 49 patients initially screened, ten met the criteria and had the operation. Six of the ten patients had complete seizure freedom, and eight had a more than 90% reduction in seizure frequency with no operative mortality and minimal morbidity (one wound infection). Of course, external funding and volunteer efforts supported this programme, and, as with any
www.thelancet.com/neurology Vol 15 August 2016
medical intervention in low-income and middle-income countries, the use of scarce health-care funding to make this sustainable should be challenged. However, Jetté and colleagues1 cite persuasive evidence that epilepsy surgery is extremely cost-effective and is associated with substantial savings in health-care expenditures over time compared with medical treatment. The enormous societal and individual costs of untreated epilepsy in all countries calls for a solution. The fact that this is only one of many daunting problems in developing countries should not diminish its importance. This is a life-threatening, profoundly disabling, and yet potentially curable condition. Making epilepsy surgery a widely accepted and accessible treatment option for all appropriate candidates, rather than a therapy of last resort or an unattainable luxury, will require the education of practitioners and the public alike, as well as innovation and investment to make it more accessible worldwide, but this can and should be done. Benjamin Warf Department of Neurosurgery, Harvard Medical School and Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115, USA [email protected] I declare no competing interests. 1
2
3 4
5
6 7
Jetté N, Sander JW, Keezer MR. Surgical treatment for epilepsy: the potential gap between evidence and practice. Lancet Neurol 2016; 15: 982–94. Rwiza HT, Kilonzo GP, Haule J, et al. Prevalence and incidence of epilepsy in Ulanga, a rural Tanzanian district: a community-based study. Epilepsia 1992; 33: 1051–56. WHO. Severe malaria. Trop Med Int Health 2014; 19 (suppl S1): 7–131. Warf BC. Hydrocephalus in Uganda: predominance of infectious origin and primary management with endoscopic third ventriculostomy. J Neurosurg 2005; 102: 1–15. Warf BC, Dagi AR, Nsbuga B, Schiff SJ. Five year survival and outcome of treatment for post-infectious hydrocephalus in Ugandan infants. J Neurosurg Pediatr 2011; 8: 502–08. Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med 2000; 342: 314–19. Boling W, Palade A, Wabulya A, et al. Surgery for pharmacoresistant epilepsy in the developing world: a pilot study. Epilepsia 2009; 50: 1256–61.
899