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Synaptic vesicle protein 2A tumoral expression predicts levetiracetam adverse events

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Abstract

Objective

The efficacy of levetiracetam (LEV) in controlling seizures in patients with brain tumor-related epilepsy (BTRE) depends on tumoral expression of synaptic vesicle protein 2A (SV2A). Although LEV is generally well tolerated, neuropsychiatric adverse events (NPAEs) might occur, limiting compliance and seizure control. We aimed to assess the influence of tumoral SV2A expression on the occurrence of LEV-related NPAEs in patients with glioma.

Methods

Specimens from patients enrolled in the multicenter COMPO study, with glioma and BTRE treated with LEV, undergoing neurosurgery were retrieved. Immunohistochemistry-based expression of SV2A in tumoral and peritumoral tissue was scored in a four-point scale from absent (score = 0) to strong (score = 3). Low immunoreactivity (IR) corresponded to scores < 2. Staining ratios (tumoral SV2A IR/peritumoral SV2A IR) were grouped into low (≤ 0.5) and high (> 0.5). NPAEs were assessed longitudinally with the Neuropsychiatry Inventory 12 test (NPI-12).

Results

Overall, 18 patients were eligible for analysis. All received LEV monotherapy, with 67% developing NPAEs. Patients with NPAEs had significantly lower median SV2A intensity score compared to patients without NPAEs (score 1 vs 0, p = 0.025). Low staining ratio (≤ 0.5) associated with higher NPAE occurrence compared to SR > 0.5 (85.7% vs 0%, p < 0.01). A SR ≤ 0.5 predicted a consistent increase in risk of NPAEs (OR 45.0; 95% CI 1.8–1128; p = 0.02).

Conclusions

Our results suggest that SV2A expression in tumoral and peritumoral tissue correlates with the occurrence of LEV-related NPAEs. Thus, considering that SV2A expression also influences LEV effectiveness, SV2A staining might help in tailoring treatment to patients.

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Funding

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Author information

Author notes

  1. Angelo Sidoni, Paolo Giovenali and Paolo Calabresi are senior authors.

  2. Michele Romoli and Martina Mandarano are equal contributors.

Authors and Affiliations

  1. Neurology Clinic, University of Perugia, S. Maria Della Misericordia Hospital, Piazzale G. Menghini 1, Perugia, Italy

    Michele Romoli, Marina Romozzi, Paolo Eusebi, Chiara Bedetti, Elena Nardi Cesarini, Angela Verzina, Carmen Calvello, Paolo Calabresi & Cinzia Costa

  2. Department of Experimental Medicine, Section of Anatomic Pathology and Histology, University of Perugia, Perugia, Italy

    Martina Mandarano, Elisabetta Loreti & Angelo Sidoni

  3. Diagnostic Cytology and Histology Unit, S. Maria Della Misericordia Hospital, Perugia, Italy

    Paolo Giovenali

  4. IRCCS Santa Lucia, Roma, Italy

    Paolo Calabresi

Authors
  1. Michele Romoli
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  2. Martina Mandarano
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  3. Marina Romozzi
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  4. Paolo Eusebi
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  5. Chiara Bedetti
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  6. Elena Nardi Cesarini
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  7. Angela Verzina
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  8. Carmen Calvello
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  9. Elisabetta Loreti
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  10. Angelo Sidoni
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  11. Paolo Giovenali
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  12. Paolo Calabresi
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  13. Cinzia Costa
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Corresponding author

Correspondence to Cinzia Costa.

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Conflicts of interest

The authors declare that they have no conflict of interest.

Ethical standards

The study was approved by the Internal Advisory Board [3] and complied with the 1964 Declaration of Helsinki and its later amendments.

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Romoli, M., Mandarano, M., Romozzi, M. et al. Synaptic vesicle protein 2A tumoral expression predicts levetiracetam adverse events. J Neurol 266, 2273–2276 (2019). https://doi.org/10.1007/s00415-019-09410-0

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  • DOI: https://doi.org/10.1007/s00415-019-09410-0

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