The withdrawal of antiepileptic drugs in patients with low-grade and anaplastic glioma

Figures & data

Table 1. Current evidence for AED withdrawal in brain tumor patients.

Study	Design	Population characteristics	Withdrawal policy	Seizure outcome
Das et al., 2012	Retrospective	169 adult patients with brain tumors (meningioma 112; LGG 57), of which 57 had epilepsy; underwent resection between 2004 and 2005	AED withdrawal or AEDs never started in 111 (meningioma 87, LGG 24) of which 16 had history of epilepsy	Seizure occurrence in 11/111 patients (9%)
			AED continuation in 58 (meningioma 25, LGG 33) of which 41 had history of epilepsy	Seizure occurrence in 28/58 patients (48%)
Khan et al., 2006	Retrospective	62 children with brain tumors (LGG 37) and history of ≥1 seizure, operated between 1985 and 2004	Withdrawal over period of 6-8 w after a median seizure-free period of 1.3 y (range 0.1–11 y)	Seizure recurrence in 17/62 patients (27%) within median time of 0.8 y (range 0.06–7.7 y)
Luyken et al., 2003	Retrospective	207 children and adult patients with low-grade brain tumors (WHO grade I–III glioma 51; other [mostly neuroepithelial] 118) and intractable epilepsy, underwent resection between 1988 and 1999	Withdrawal in 67/169 (40%) patients who had become seizure free	Seizure recurrence in 18/169 (11%) patients who had become seizure free (unknown seizure recurrence rate in withdrawal group)

w: week; y: year; LGG: low-grade glioma.

Table 2. Factors to consider before withdrawing antiepileptic drugs in glioma patients.

		Lower risk of seizure recurrence/higher benefit from AED withdrawal	Higher risk of seizure recurrence/lower benefit from AED withdrawal
Tumor-related factors	Tumor grade and molecular-genetic profile	Anaplastic glioma and GBM	Low-grade glioma and glioneural tumors
	Tumor location	Midline, occipital lobe	Insular, frontal, and temporal lobe
	Duration of stable tumor disease after antitumor treatment	Long-term stable disease	Short-term stable disease
	Patient’s prognosis at time of withdrawal	Low risk of short-term tumor recurrence	High risk of short-term tumor recurrence
Seizure characteristics	Seizure type	Generalized seizures	Partial seizures
	Seizure frequency before development of seizure freedom	Low seizure frequency	High seizure frequency
	Initial seizure severity	No history of status epilepticus	History of status epilepticus
	Duration of seizure freedom	Long-term seizure freedom	Short-term seizure freedom
Antitumor treatment	Type of antitumor treatment	Resection	Radiotherapy or chemotherapy
	In case of surgical resection: extent of resection	Total resection	Subtotal or partial resection
Side effects	Short-term and long-term AED side effects	Serious side effects affecting daily life	No/limited side effects
	Drug–drug interactions	Unwanted drug–drug interactions with for example dexamethasone or chemotherapy, particularly enzyme-inducing AEDs	No/limited interactions or use of valproic acid or levetiracetam during TMZ treatment in GBM, as it might affect survival
	Teratogenic risk	AEDs (especially AED polytherapy or use of valproic acid or carbamazepine) in women of childbearing age	Women of non-childbearing age/men
Patient-related factors	Possible psychosocial impact of epilepsy and using AEDs	Experiencing inconvenience of taking AEDs; feeling medicalized due to long-term use of AEDs	Risk of being stigmatized in case of a seizure; fear of seizure-related injuries
	Effect of withdrawal or seizure relapse on driver’s license	No suspension of driver’s license during or after AED withdrawal	Fear of losing driver’s license in case of seizure relapse
	Financial burden of long-term AED use	Limited insurance coverage leading to substantial expenses	AEDs fully covered by medical insurance

AED: Antiepileptic drug; TMZ: temozolomide.