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Current evidence supports surgery as the intervention most likely to achieve long\u2010term seizure freedom, but no specific guidelines are available on TSC pre\u2010surgical workup. This critical review assesses which TSC patients are suitable for surgical treatment, when pre\u2010surgical evaluation should start, and what degree of surgical resection is optimal for postsurgical outcome.<\/jats:p><jats:p><jats:italic>Methods<\/jats:italic>: We searched for publications from 2000 to 2020 in Pubmed and Embase using the terms \u201ctuberous sclerosis,\u201d \u201cepilepsy,\u201d and \u201cepilepsy surgery\u201d. To evaluate postsurgical seizure outcome, we selected only studies with at least one year of follow\u2010up.<\/jats:p><jats:p><jats:italic>Results<\/jats:italic>: Overall, we collected data on 1,026 patients from 34 studies. Age at surgery ranged from one month to 54 years. Mean age at surgery was 8.41 years. Of the diagnostic non\u2010invasive pre\u2010surgical tools, MRI and video\u2010EEG were considered most appropriate. Promising data for epileptogenic tuber detection is provided from invasive SEEG studies. Data on surgery and related outcome were available for 769 patients. Seizure freedom was seen in 64.4% of patients who underwent tuberectomy, 68.9% treated with lobectomy and 65.1% with multilobar resection. The most effective surgical approach was lobectomy, even though more recently tuberectomy associated with the resection of the perituberal area seems to be the best approach to reach seizure freedom. Published postsurgical seizure freedom rates in patients with TSC were between 65% and 75%, but reduced to 48%\u201057% over longer follow\u2010up periods. Early surgery might positively affect neurodevelopmental trajectory in some patients, even though data on cognitive outcome are still to be confirmed with longitudinal studies.<\/jats:p><jats:p><jats:italic>Significance<\/jats:italic>: Considering the strong correlation between epilepsy duration and neurocognitive outcome, all patients with TSC ought to be referred early to a dedicated epilepsy centre for individually tailored pre\u2010surgical evaluation by a multi\u2010disciplinary epilepsy surgery team.<\/jats:p>","DOI":"10.1684\/epd.2021.1253","type":"journal-article","created":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T13:11:02Z","timestamp":1615813862000},"page":"53-73","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Surgery for drug\u2010resistant tuberous sclerosis complex\u2010associated epilepsy: who, when, and 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