Epigraph Vol. 26 Issue 2, Spring 2024

Response from Dr. Hector H. Garcia to “Neurocysticercosis as the main cause of epilepsy: A misdiagnosis that should be avoided”

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Cite this article: Garcia HH. Response from Dr. Hector H. Garcia to “Neurocysticercosis as the main cause of epilepsy: A misdiagnosis that should be avoided.” Epigraph 2024; 26(2):76-78.

Dear Editors,

There is abundant and consistent evidence of the association between neurocysticercosis (NCC) and epilepsy and its contribution to the burden of disease, both in terms of more NCC in imaging studies, or more specific antibodies (and stronger reactions) in individuals with epilepsy than in the general population1,2—the latter despite the fact that a significant proportion of individuals with NCC have calcified parasites only.

Epidemiologically, this large body of evidence can only be explained by three scenarios:

  1. Cysticercosis causes epilepsy.
  2. One or more confounding factors are associated with both cysticercosis and epilepsy.
  3. Epilepsy causes cysticercosis.

To save readers from sterile discussions or nonsense arguments like #3, I will limit this response to a quick, not comprehensive listing of concrete evidence of the association between neurocysticercosis and epilepsy, and its magnitude.

  • In endemic areas, individuals with NCC compose a significant proportion of patients in epilepsy clinics, with a typical presentation of months or years with seizures of the same type (clearly not compatible with acute symptomatic seizures).3-5
  • In most cases, the seizures have a strong topographic correlate with the localization of one of the cysts (plus a demonstrated relation between neurocysticercosis outside the hippocampal region and hippocampal atrophy, which explains temporal seizures in an additional subset of cases).6-8
  • There is now consistent evidence from animal models, and some from human specimens, demonstrating chronic brain inflammation and damage around cysticercal cysts.9
  • Contrary to what is affirmed in Carpio and Gigante's letter, longitudinal studies demonstrate both the contribution of neurocysticercosis to the incidence of epilepsy (an Ecuadoran study), as well as the high proportion of late seizure relapses in diverse types of neurocysticercosis.10-12 It should be noted that calling the initial seizures "acute symptomatic seizures" in these cases leads to short-term use of anti-seizure medication only, exposing patients to unnecessary risk.13
  • Additional longitudinal data demonstrate that early destruction of cysts using anti-parasitic and anti-inflammatory drugs results in fewer seizure relapses.14-16

In medicine, perceptions vary and conclusions sediment with time and evidence. Over the years, we have witnessed voices claim that anti-parasitic drugs were useless to destroy cysticerci17, that killing the cysts does not carry any benefit for the evolution of the seizure disorder13,18, and other misconceptions that resolved as evidence accumulated. In this case, however, there is already more than enough data to sustain that neurocysticercosis is a major contributor to the worldwide burden of epilepsy. More and larger epidemiologic studies, particularly in areas where NCC is endemic, should help to estimate with greater precision the exact magnitude of the impact of NCC in the burden of epilepsy.

Sincerely,

Hector H. Garcia, MD, PhD
Head, Cysticercosis Unit of the National Institute of Neurological Sciences, Lima, Peru
Director, Center for Global Health at the Universidad Peruana Cayetano Heredia, Lima, Peru
Adjunct Professor, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

References

  1. Ndimubanzi PC, Carabin H, Budke CM, Nguyen H, Qian YJ, Rainwater E, Dickey M, Reynolds S, Stoner JA. A systematic review of the frequency of neurocysticercosis with a focus on people with epilepsy. PLoS Negl Trop Dis. 2010 Nov 2;4(11):e870
  2. Nicoletti A, Edoardo Cicero C, Todaro V, Colli C, Cosmi F, Anselmi M, Caicedo C, Vilte E, Mario Camargo W, Bartoloni A, Crespo Gomez EB, Giuliano L. Epilepsy and neurocysticercosis in rural areas of the Bolivian Chaco: What has changed during the last 30 years? Epilepsia Open. 2024 Apr;9(2):513-521.
  3. Stelzle D, Makasi C, Schmidt V, Trevisan C, van Damme I, Welte TM, Ruether C, Fleury A, Dorny P, Magnussen P, Zulu G, Mwape KE, Bottieau E, Gabriël S, Ngowi BJ, Winkler AS; SOLID collaborators. Epidemiological, clinical and radiological characteristics of people with neurocysticercosis in Tanzania-A cross-sectional study. PLoS Negl Trop Dis. 2022 Nov 28;16(11):e0010911.
  4. Stelzle D, Schmidt V, Keller L, Ngowi BJ, Matuja W, Escheu G, Hauke P, Richter V, Ovuga E, Pfausler B, Schmutzhard E, Amos A, Harrison W, Kaducu J, Winkler AS. Characteristics of people with epilepsy and Neurocysticercosis in three eastern African countries-A pooled analysis. PLoS Negl Trop Dis. 2022 Nov 7;16(11):e0010870.
  5. Rivera D, Santos D, Carmant L, García HH, Pimentel R, Wiebe S, Aponte V, González L, Castillo JC, Matos B, Paliza JM, Fermín R, Stoeter P, Pérez-Then E. Diagnóstico de neurocisticercosis en pacientes con epilepsia residentes en el suroeste de la República Dominicana [Diagnosis of neurocysticercosis in patients with epilepsy living in the south-western Dominican Republic]. Rev Neurol. 2024 Feb 16;78(4):109-116.
  6. Duque KR, Escalaya AL, Zapata W, Burneo JG, Bustos JA, Gonzales I, Saavedra H, Pretell EJ, Garcia HH; Cysticercosis Working Group in Peru. Clinical topography relationship in patients with parenchymal neurocysticercosis and seizures. Epilepsy Res. 2018 Sep;145:145-152.
  7. Duque KR, Burneo JG. Clinical presentation of neurocysticercosis-related epilepsy. Epilepsy Behav. 2017 Nov;76:151-157.
  8. Bianchin MM, Velasco TR, Wichert-Ana L, Araújo D Jr, Alexandre V Jr, Scornavacca F, Escorsi-Rosset SR, dos Santos AC, Carlotti CG Jr, Takayanagui OM, Sakamoto AC. Neuroimaging observations linking neurocysticercosis and mesial temporal lobe epilepsy with hippocampal sclerosis. Epilepsy Res. 2015 Oct;116:34-9.
  9. Mejia Maza A, Carmen-Orozco RP, Carter ES, Dávila-Villacorta DG, Castillo G, Morales JD, Mamani J, Gavídia CM, Alroy J, Sterling CR, Gonzalez AE, García HH, Woltjer RL, Verástegui MR, Gilman RH; Cysticercosis Working Group in Peru. Axonal swellings and spheroids: a new insight into the pathology of neurocysticercosis. Brain Pathol. 2019 May;29(3):425-436.
  10. Del Brutto OH, Recalde BY, Mera RM. Incidence of Adult-Onset Epilepsy and the Contributory Role of Neurocysticercosis in a Five-Year, Population-Based, Prospective Study in Rural Ecuador. Am J Trop Med Hyg. 2021 Oct 11;106(1):208-214
  11. Nash TE, Pretell EJ, Lescano AG, Bustos JA, Gilman RH, Gonzalez AE, Garcia HH; Cysticercosis Working Group in Peru. Perilesional brain oedema and seizure activity in patients with calcified neurocysticercosis: a prospective cohort and nested case-control study. Lancet Neurol. 2008 Dec;7(12):1099-105.
  12. Verma A, Kumar A, Sachan D. Clinical characteristics and risk factors for seizures to recur in calcified neurocysticercosis : Prospective cohort Study. Acta Neurol Taiwan. 2024 Dec 30;33(4):153-160. PMID: 38030224.
  13. Carpio A, Hauser WA. Prognosis for seizure recurrence in patients with newly diagnosed neurocysticercosis. Neurology. 2002 Dec 10;59(11):1730-4
  14. Garcia HH, Pretell EJ, Gilman RH, Martinez SM, Moulton LH, Del Brutto OH, Herrera G, Evans CA, Gonzalez AE; Cysticercosis Working Group in Peru. A trial of antiparasitic treatment to reduce the rate of seizures due to cerebral cysticercosis. N Engl J Med. 2004 Jan 15;350(3):249-58
  15. Garcia HH, Gonzales I, Lescano AG, Bustos JA, Zimic M, Escalante D, Saavedra H, Gavidia M, Rodriguez L, Najar E, Umeres H, Pretell EJ; Cysticercosis Working Group in Peru. Efficacy of combined antiparasitic therapy with praziquantel and albendazole for neurocysticercosis: a double-blind, randomised controlled trial. Lancet Infect Dis. 2014 Aug;14(8):687-695.
  16. Romo ML, Wyka K, Carpio A, Leslie D, Andrews H, Bagiella E, Hauser WA, Kelvin EA; Ecuadorian Neurocysticercosis Group. The effect of albendazole treatment on seizure outcomes in patients with symptomatic neurocysticercosis. Trans R Soc Trop Med Hyg. 2015 Nov;109(11):738-46. doi: 10.1093/trstmh/trv078.
  17. Carpio A, Santillán F, León P, Flores C, Hauser WA. Is the course of neurocysticercosis modified by treatment with antihelminthic agents? Arch Intern Med. 1995 Oct 9;155(18):1982-8.
  18. Carpio A, Romo ML. The relationship between neurocysticercosis and epilepsy: an endless debate. Arq Neuropsiquiatr. 2014 May;72(5):383-90.

Read the letter: Neurocysticercosis as the main cause of epilepsy: A misdiagnosis that should be avoided