Precision medicine approaches in epilepsy: A systematic review of genetic markers and personalized treatment strategies
Received date: 10 Feb 2024
Revised date: 27 May 2024
Accepted date: 03 Jun 2024
Copyright
Epilepsy is one of the most common neurological diseases globally. We conducted a systematic review of the genetic markers and personalized treatment strategies used in the precision medicine treatment of epilepsy. An exhaustive electronic search was carried out on PubMed and Google Scholar, spanning from inception up to June 2023 on epilepsy and biomarkers. A total of 45 articles from PubMed and 19 articles from Google Scholar were imported and screened based on studies that focused primarily on genetic markers and precision methods for epilepsy subtyping, treatment strategies, outcomes, and adverse effects. Reviews and studies not in English were excluded. Full-text data extraction, coding, and analysis were carried out with Microsoft Excel. For the risk of bias assessment of the final included studies, the Critical Appraisal Skills Program checklist was used. A total of 19 studies were analyzed in the review. The SLC35A2 gene saw a reduction in seizure frequency with D-galactose treatment while the KCNQ2 gene saw improvement with phenytoin, carbamazepine, and retigabine. GRIN2D gene saw varying improvements with memantine. KCNT1 gene saw improvement with only a combination of quinidine and topiramate, quinidine was not useful when used alone. Other studies involved the identification of different markers using gene and exome sequencing. These studies collectively provide a diverse range of insights into epilepsy, with variations in study design, sample size, age groups, and diagnostic criteria, highlighting the multifaceted nature of epilepsy research. These studies contribute to our understanding of epilepsy diagnosis and management in different clinical settings, however, there were some limitations such as QT prolongation was observed with specific medications and participant heterogeneity. Small sample sizes reduced statistical power and brief durations of studies limited their ability for long-term analysis. Although most studies had a low risk of bias, two studies demonstrated some reporting bias. Fianlly, the absence of biomarkers is a limitation that impedes the study's capacity to explore underlying biological mechanisms.
Key words： genetic markers; in epilepsy; precision medicine
Aman Agarwal , Ravneet Kaur , Faiza Ashfaque , Zeenat Hadi , Muhammad Wajeeh Anis , Ahila Ali , Simran Ochani , Al Hasibuzzaman . Precision medicine approaches in epilepsy: A systematic review of genetic markers and personalized treatment strategies[J]. Precision Medical Sciences, 2024 , 13(2) : 72 -83 . DOI: 10.1002/prm2.12139
| 1 |
World Health Organization. Epilepsy. 2022
|
| 2 |
Pitkänen A, Ndode-Ekane XE, Lapinlampi N, Puhakka N. Epilepsy biomarkers—toward aetiology and pathology specificity. Neurobiol Dis. 2019;123:42-58.
|
| 3 |
Boerma RS, Braun KP, van den Broek MP, et al. Remarkable phenytoin sensitivity in 4 children with SCN8A-related epilepsy: a molecular neuropharmacological approach. Neurotherapeutics. 2016;13(1):192-197.
|
| 4 |
Perucca P, Scheffer IE, Harvey AS, et al. Real-world utility of whole exome sequencing with targeted gene analysis for focal epilepsy. Epilepsy Res. 2017;131:1-8.
|
| 5 |
Mullen SA, Carney PW, Roten A, et al. Precision therapy for epilepsy due to KCNT1 mutations: a randomized trial of oral quinidine. Neurology. 2018;90(1):e67-e72.
|
| 6 |
Amadori E, Brolatti N, Scala M, et al. Precision medicine in early-onset epilepsy: the KCNQ2 paradigm. J Transl Genet Genom. 2020;4(3):278-284.
|
| 7 |
de Jong J, Cutcutache I, Page M, et al. Towards realizing the vision of precision medicine: AI-based prediction of clinical drug response. Brain. 2021;144(6):1738-1750.
|
| 8 |
Kearney JA. Precision medicine: NMDA receptor-targeted therapy for GRIN2D encephalopathy. Epilepsy Curr. 2017;17(2):112-114.
|
| 9 |
Kravetz MC, Viola MS, Prenz J, Curi M, Bramuglia GF, Tenembaum S. Case report of novel genetic variant in KCNT1 channel and pharmacological treatment with quinidine. Precision medicine in refractory epilepsy. Front Pharmacol. 2021;12:648519.
|
| 10 |
Madaan P, Jauhari P, Gupta A, Chakrabarty B, Gulati S. A quinidine nonresponsive novel KCNT1 mutation in an Indian infant with epilepsy of infancy with migrating focal seizures. Brain Dev. 2018;40(3):229-232.
|
| 11 |
Mir A, Qahtani M, Bashir S. GRIN2A-related severe epileptic encephalopathy treated with memantine: an example of precision medicine. J Pediatr Genet. 2020;9(4):252-257.
|
| 12 |
Andrade DM. Time is brain: the importance of an accurate SCN1A prediction score in the era of precision medicine. Epilepsy Curr. 2022;22(4):231-233.
|
| 13 |
Esterhuizen AI, Tiffin N, Riordan G, et al. Precision medicine for developmental and epileptic encephalopathies in Africa-strategies for a resource-limited setting. Genet Med. 2023;25(2):100333.
|
| 14 |
Truty R, Patil N, Sankar R, et al. Possible precision medicine implications from genetic testing using combined detection of sequence and intragenic copy number variants in a large cohort with childhood epilepsy. Epilepsia Open. 2019;4(3):397-408.
|
| 15 |
Aledo-Serrano Á, Valls-Carbó A, Fenger CD, et al. D-Galactose supplementation for the treatment of mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE): a pilot trial of precision medicine after epilepsy surgery. Neurotherapeutics. 2023;20:1294-1304.
|
| 16 |
Glauser T, Laurenza A, Yang H, Williams B, Ma T, Fain R. Efficacy and tolerability of adjunct perampanel based on number of antiepileptic drugs at baseline and baseline predictors of efficacy: a phase III post-hoc analysis. Epilepsy Res. 2016;119:34-40.
|
| 17 |
Grover S, Talwar P, Gourie-Devi M, et al. Genetic polymorphisms in sex hormone metabolizing genes and drug response in women with epilepsy. Pharmacogenomics. 2010;11(11):1525-1534.
|
| 18 |
Yang L, Kong Y, Dong X, et al. Clinical and genetic spectrum of a large cohort of children with epilepsy in China. Genet Med. 2019;21(3):564-571.
|
| 19 |
Balestrini S, Chiarello D, Gogou M, et al. Real-life survey of pitfalls and successes of precision medicine in genetic epilepsies. J Neurol Neurosurg Psychiatry. 2021;92(10):1044-1052.
|
| 20 |
Goldstein HE, Poliakov A, Shaw DW, et al. Precision medicine in pediatric temporal epilepsy surgery: optimization of outcomes through functional MRI memory tasks and tailored surgeries. J Neurosurg Pediatr. 2022;30:272-283.
|
| 21 |
Muchada IF, Wilmshurst JM, Laing N, Haf Davies E, Fieggen K. A qualitative study exploring caregivers' experiences, perspectives, and expectations for precision medicine in epilepsy in South Africa. Epilepsy Behav. 2021;117:107873.
|
| 22 |
Maes M, Barbosa DS, Almulla AF, Kanchanatawan B. A novel pathway phenotype of temporal lobe epilepsy and comorbid psychiatric disorders: results of precision nomothetic medicine. Antioxidants. 2022;11(5):803.
|
| 23 |
Witters P, Tahata S, Barone R, et al. Clinical and biochemical improvement with galactose supplementation in SLC35A2-CDG. Genet Med. 2020;22(6):1102-1107.
|
| 24 |
Kang H-J, Kim D-S, Kim SH, et al. Epilepsy with SLC35A2 brain somatic mutations in mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE). Ann Child Neurol. 2022;30(3):88-94.
|
| 25 |
Pisano T, Numis AL, Heavin SB, et al. Early and effective treatment of KCNQ2 encephalopathy. Epilepsia. 2015;56(5):685-691.
|
| 26 |
Mikati MA, Jiang YH, Carboni M, et al. Quinidine in the treatment of KCNT1-positive epilepsies. Ann Neurol. 2015;78(6):995-999.
|
| 27 |
Kutluk G, Randa NC. Preliminary study about a significant and treatable cause of epileptic encephalopathy: GRIN2D mutation. Acta Med Alanya. 2021;5(2):109-117.
|
| 28 |
Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.
|
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