Aabiya Arif  ( Ziauddin Medical College. )
Zara Shah  ( Department of Surgery, Aga khan University Hospital, Karachi, Pakistan. )
Muhammad Waqas Saeed Baqai  ( Department of Surgery, Aga khan University Hospital, Karachi, Pakistan. )
Muhammad Shahzad Shamim  ( Department for Surgery, Aga Khan University, Karachi, Pakistan. )

Up to 88% of patients with low grade glioma (LGG) experience seizures during the course of their disease. In patients who undergo surgery for supratentorial low grade glioma (SLGG), post-operative seizures can impact their quality of life and complicate the post-operative management course. Evidence suggests that epileptic activity can be related to tumour progression. In addition to the extent of resection, recent studies have investigated the possible patient and tumour factors which can influence post-operative seizure control in patients with SLGG.

 

Keywords: Low grade glioma; supratentorial; postoperative seizures.

 

DOI: 10.47391/JPMA.06-23

 

Introduction

 

Low-grade gliomas (LGG) are reported to be tumours with the most epileptogenic potential. 60-88% of patients with LGG experience seizures during the course of their disease, out of which 10-45% of patients experience seizures in the late stages of their clinical course.1-3 In fact, epileptic seizures is the most common symptom experienced by patients with supratentorial LGG (SLGG)4  The interplay between LGG and seizures is thought to be multifactorial and is not fully understood. However, some studies have shown evidence regarding the mechanism of glioma progression and epileptic activity to be related.5 This phenomenon gives reasoning as to why LGG resection and the extent of resection are one of the factors influencing post-operative seizure control.4,6 In addition, several other factors also potentially affect post-operative seizure control in these patients. In this paper, we have reviewed some of the recent literature on factors influencing post-operative seizure control in patients with SLGG.

 

Review of literature

 

A retrospective study by Still et al., included 346 patients with grade II diffuse SLGG who presented with seizures and were treated solely by surgical resection. A follow-up of 6 months from the surgical resection was done to assess post-operative seizure control, where seizure control was defined as no epileptic activity post-surgery irrespective of the use of any anti-epileptic medication (AEM) (1A Engel classification system). In all patients, maximum surgical resection was aimed with the aid of intra-operative cortical and subcortical functional mapping and direct electric stimulation for awake patients. The mean EOR was 74.7 ± 24.8%, and the mean residual volume was reported to be 18.4 ± 28.2 cc. Post surgically, 227 (65.5%) patients met the criteria of 1A Engel class, in which 38 patients had seizure control without using anti-epileptic medication. 40 (11.6%) met the requirements for Engel class 1B, 1C, and 1D, 61(17.6%) were classified as Engel class 2 and 3, and 18 patients (5.2%) belonged to Engel class 4. Univariate analysis revealed age (p=0.023), pre-operative tumour volume (p=0.014), the extent of resection (p<0.001), and residual tumour (p<0.001) to be predictors of post-operative seizure control. However, multivariate analysis showed only higher age at resection (adjusted OR per unit, 1.03 [95% CI:1.01-1.06],P = .043) and greater tumour resection (adjusted OR per unit, 1.02 [95% CI:1.00-1.03], P < .001) to be significant independent predictors. In addition, an EOR greater than or equal to  91% and residual tumour less than or equal to 19cc predicted better post-operative seizure control.7

Another study by Hongxiang Jiang et al., included 70 patients with primary SLGG who were diagnosed with seizures with electroencephalogram (EEG), according to the  International League Against Epilepsy (ILAE). All patients received one or more AEM post-surgery; 39 (55.7%)  patients received one AEM, while others received more than one AED post-operatively. Patients who required adjuvant treatment underwent chemotherapy and radiotherapy: 33 (47.1%) received temozolomide, and 30 (42.9%) received radiotherapy. The minimum follow-up post-surgery in this study was 12 months. Engel classification was used to classify patients into seizure-free or seizure relapse groups. In total, 54 (77.1%) patients had post-operative seizure control (Engel class I), whereas 16 (22.9%) patients had seizure relapse (Engel classes II-IV). Univariate analysis revealed that pre-operative seizure frequency (p=0.001), location of the lesion (p=0.058), the extent of resection (0.025), IDH1 mutation (p=0.035), and chemotherapy with temozolomide post-surgery (p=0.043) were all factors influencing post-operative seizure control. Multivariate analysis showed pre-operative seizure frequency (adjusted OR, 2.05 [95% CI: 1.01- 2.13], p=0.03), extent of resection (adjusted OR, 3.38 [95% CI: 2.49-5.59], P=0.02), IDH1 status (adjusted OR, 0.53 [95% CI: 0.42-1.46], P=0.01), chemotherapy with temozolomide (adjusted OR, 2.13  [95% CI: 2.01-2.65], P<0.01) were all independent predictors of post-operative seizure control.8

 

Tamara Ius et al., had a total of 155 patients with diffuse SLGG after the first-line surgery. Post-operative seizure control was assessed at 4, 8, 12, and 18 months, which revealed that 110 (70.97%) patients had complete seizure control (Engel class IA), 16 (10.32%), 23(14.84%), and 6 (3.87%) patients met the criteria for Engel class IB-ID, Engel class II-III, and Engel class IV, respectively. Univariate analysis revealed the frequency of pre-operative seizures, seizure onset features, pre-operative ∆T2T1MRI index, molecular class (astrocytoma IDH1/2 mutated 1p-19q non-codeleted, astrocytoma IDH1/2 wild type, oligodendroglioma IDH1/2 mutated 1p-19q co deleted, MGMT methylation), EOR, single or multiple AEDs prescribed, and the residual tumour is all factors affecting post-operative seizure control. Multivariate analysis only showed age (adjusted OR, 1.056 [95% CI:1.010–1.103], P=0.014), ∆T2T1MRI index (adjusted OR, 1.077,  [95% CI:1.102–1.134], P= 0.016), and EOR (adjusted OR, 0.957  [95% CI: 0.920–0.995], P=0.030) to be independent predictors of post-operative seizure control in SLGG. in addition, the receiver operating characteristic curve showed better seizure control when EOR ≥ 85%, residual tumour ≤15 cm3, and pre-operative ∆T2T1 MRI index≤18 cm3, with a predictive accuracy of 72.90%, 73.55%, and 82.65%, respectively.9

 

Conclusion

 

The percentage of patients in the three studies that gained post-operative seizure control (Engel Class IA) was 65.5%, 77.1%, and 70.97%, indicating that the number of people who were seizure-free after surgery, is much greater than those who were not. All three studies report EOR as an independent predictor of the outcome; two report age as an independent predictor, and only one found pre-operative seizure frequency, IDH1 status, and adjunct chemotherapy with temozolomide to be independent predictors of post-operative seizure control in SLGG. 

 

References

 

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