Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jul 8;22(1):250.
doi: 10.1186/s12883-022-02762-7.

Perioperative levetiracetam for seizure prophylaxis in seizure-naive brain tumor patients with focus on neurocognitive functioning

Elias Konrath #  1   2 , Franz Marhold #  3   4 , Wolfgang Kindler  3   5 , Florian Scheichel  3   4 , Branko Popadic  3   4 , Katrin Blauensteiner  3   5 , Bernadette Calabek  3   5 , Elisabeth Freydl  3   5 , Michael Weber  6 , Robin Ristl  7 , Katharina Hainz  5 , Camillo Sherif  3   4 , Stefan Oberndorfer  3   5   8
Affiliations

Perioperative levetiracetam for seizure prophylaxis in seizure-naive brain tumor patients with focus on neurocognitive functioning

Elias Konrath et al. BMC Neurol. .

Abstract

Introduction: In seizure-naive brain tumor patients, the efficacy of perioperative prophylactic antiepileptic drug treatment remains controversial. In case of administration, the common preferred drug is levetiracetam (LEV) because of its favorable pharmacological profile. Research to date has not sufficiently determined how LEV affects cognition in the short term, as is the case in the perioperative period. The objective of this prospective study was to examine the neurocognitive functioning of seizure-naive brain tumor patients after receiving LEV perioperatively.

Methods: Fortythree patients with supratentorial brain tumor scheduled for surgery received LEV three days before until six days after surgery as seizure prophylaxis. Cognitive functioning (NeuroCogFX), LEV plasma-levels, hematotoxicity, side-effects, as well as health-related quality of life (HRQoL, Qolie31), were recorded preoperatively before (Baseline) and after onset of LEV (Pre-Op), 4-6 days postoperatively (Post-Op) and 21 days postoperatively (Follow-Up).

Results: No significant changes in cognitive functioning and HRQoL were seen after onset of preoperative LEV. There was a significant improvement of NeuroCogFX total-score at Follow-Up (p = 0.004) compared to Baseline. The overall-score Qolie31 showed simultaneous improvement patterns as cognitive functioning (p < 0.001). The most frequent side effect related to study drug was somnolence (in 28.6% of patients).

Conclusions: A significant improvement of cognitive functioning, as well as an improvement in HRQoL, were detected postoperatively. This is presumably due to the debulking effect of the surgery. Nevertheless, LEV has no detrimental effect on cognitive functioning in the perioperative phase in seizure-naive brain tumor patients.

Trial registration: This study was registered prospectively (Date: 25/11/2015; EudraCT: 2015-003,916-19).

Keywords: Brain tumor; Cognition; Cognitive functioning; Perioperative seizure prophylaxis; Surgery.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Study Design and Procedures. Patients received LEV during a perioperative period of nine days. Levetiracetam plasma levels were measured two days after onset of LEV administration and three days postoperative. Hematotoxicity was measured through blood samples one week after surgery. Neuropsychological assessment (NeuroCogFX), including HRQoL questionnaire (QOLIE-31) and self-reported side effects, was conducted at four timepoints: one day before administration of levetiracetam (Baseline/no LEV), on the second day after onset of levetiracetam administration (Pre-Op/with LEV), four to six days after surgery (Post-Op/with LEV) and three weeks after surgery (Follow-Up/no LEV). The total study duration was 25 days
Fig. 2
Fig. 2
Flow chart of patient inclusion and dropouts. Inclusion criteria comprised seizure-naive, adult patients (> 18 years) with a suspected primary supratentorial brain tumor and a planned surgery. Exclusion criteria included contraindication against LEV and pre-existing anticonvulsive medication
Fig. 3
Fig. 3
(A) Estimated marginal means and corresponding standard error bars in standard value points across the four timepoints for the cognitive domain scores and Total score. Neuropsychological assessment of cognitive functioning was measured at four timepoints (Fig. 1). Total Score consists of the following domains: attention, working memory, memory and language. Which subtests constitute domains, see methods section. (B) Estimated marginal mean differences and corresponding 95%, Bonferroni adjusted confidence intervals of standard value points for cognitive domain scores and Total score between Pre-Op and Baseline testing. Cognitive functioning at Baseline (no levetiracetam) was measured one day before administration of levetiracetam and at Pre-Op (with levetiracetam) on the third day after onset of levetiracetam administration. Vertical dotted line represents the clinically meaningful deterioration margin. Bonferroni adjustment was made for six pairwise comparisons. Total Score consists of the domain attention, working memory, memory, and language. Which subtests constitute domains, see methods section
See this image and copyright information in PMC

References

    1. Walbert, T., et al., SNO and EANO practice guideline update: Anticonvulsant prophylaxis in patients with newly diagnosed brain tumors. Neuro Oncol, 2021. - PMC - PubMed
    1. Greenhalgh, J., et al., Antiepileptic drugs as prophylaxis for postcraniotomy seizures. Cochrane Database Syst Rev, 2020. 4: p. CD007286. - PMC - PubMed
    1. Glantz, M.J., et al., Practice parameter: anticonvulsant prophylaxis in patients with newly diagnosed brain tumors. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology, 2000. 54(10): p. 1886–93. - PubMed
    1. Spena G, et al. Brain tumors in eloquent areas: A European multicenter survey of intraoperative mapping techniques, intraoperative seizures occurrence, and antiepileptic drug prophylaxis. Neurosurg Rev. 2017;40(2):287–298. doi: 10.1007/s10143-016-0771-2. - DOI - PubMed
    1. Dewan MC, et al. Prophylactic antiepileptic drug administration following brain tumor resection: results of a recent AANS/CNS Section on Tumors survey. J Neurosurg. 2017;126(6):1772–1778. doi: 10.3171/2016.4.JNS16245. - DOI - PubMed