Synaptic vesicle protein 2A tumoral expression predicts levetiracetam adverse events

Michele Romoli, Martina Mandarano, Marina Romozzi, Paolo Eusebi, Chiara Bedetti, Elena Nardi Cesarini, Angela Verzina, Carmen Calvello, Elisabetta Loreti, Angelo Sidoni, Paolo Giovenali, Paolo Calabresi, Cinzia Costa

Risultato della ricerca: Contributo in rivistaArticolo in rivista

2 Citazioni (Scopus)


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.
Lingua originaleEnglish
pagine (da-a)2273-2276
Numero di pagine4
RivistaJournal of Neurology
Stato di pubblicazionePubblicato - 2019


  • Adult
  • Adverse events
  • Aged
  • Anticonvulsants
  • Antiepileptic drugs
  • Biomarkers
  • Brain Neoplasms
  • Brain tumor
  • Epilepsy
  • Female
  • Gene Expression
  • Glioma
  • Humans
  • Levetiracetam
  • Male
  • Membrane Glycoproteins
  • Mental Disorders
  • Middle Aged
  • Nerve Tissue Proteins
  • Predictive Value of Tests
  • Prospective Studies


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