The Spectrum of Long-term Epilepsy-associated Tumors: Long-term Seizure and Tumor Outcome and Neurosurgical Aspects
Luyken C, Blumcke I, Fimmers R, Urbach H, Elger CE, Wiestler OD, Schramm J;
Commented by , 29 Jul 2003
Background
Neuroepithelial neoplasms are an important cause of chronic refractory epilepsy, being responsible for up to 30% of such epilepsies in some series. Long-term data on seizure and tumor outcome in these patients is surprisingly scarce.
Aim
To determine histological spectrum and long-term seizure and oncologic outcome of surgically resected tumors associated with chronic epilepsy.
Methods
Analysis of 207 consecutive patients (age 2-54 years) with at least 2-year history of drug refractory epilepsy who underwent >50% resection of supratentorial neuroepithelial tumors. Resection procedures were aimed at removing both the tumor and the epileptogenic focus.
All patients had pre- and postoperative MRIs and none (except for 2 with malignant tumor recurrence and 2 with anaplastic astrocytoma) underwent radio- or chemotherapy after the first surgery. Follow-up data were prospectively updated.
Results
Most tumors were located in the temporomesial lobe. At histological classification, there were 154 classic epilepsy-associated tumors (ganglioglioma, dysembrioplastic neuroepithelial tumors, pleomorphic xanthoastrocytomas and pylocitic astrocytomas), 38 astrocytomas and 15 oligodendrogliomas. Four tumors (3 astrocytomas and 1 ganglioglioma) were WHO grade III.
After a median follow up of 8 years (range 2-14), 82% of patients were seizure-free (Engel class I).
Predictors of seizure freedom included a shorter history of epilepsy, a single EEG focus, absence of hippocampal sclerosis or cortical dysplasias, complete tumor resection and non-astrocytoma tumors.
After 5 years, only 9 (4%) patients had tumor recurrence and, of these, two had malignant transformation and died. Patients with astrocytomas grade II or III had a 10-year survival rate of 90%.
Discussion
This study is of interest for several reasons:
- It is one of the largest series of epilepsy-associated neuroepithelial tumors, with careful diagnostic and post-operative work-up. Unlike other series, biopsy patients were excluded because the epileptogenic focus had to be removed.
- Both seizure and oncologic outcome were followed-up for a remarkably long period, without confounding effects from radio- or chemotherapies (except for 4 cases)
- Compared with other series (ref. 1), seizure outcome was remarkably favourable with seizure-freedom in over 80%, despite a restricted extent of resection. Interestingly, 11 of 38 primary non-seizure-free patients became seizure-free after 2-6 years
- Of seizure-free patients, 41% were successfully taken off antiepileptic drugs. However, the authors do not report in how many cases drug withdrawal was attempted but did not succeed
- Tumor type influenced seizure outcome: gangliogliomas and oligodendrogliomas became seizurefree in >90%, compared with < 70% for astrocytomas grade II and pilocytic astrocytomas.
- Oncologic outcome was also very good: a 10-year survival rate of 90% (and a 10-year recurrence of only 25%) for WHO grade II or III astrocytomas is most remarkable, particularly because since these tumors had a mean preoperative history of 12 years. This contradicts the hypothesis (ref. 2) that all low-grade gliomas have a similar history. It is unclear why grade II-III astrocytomas associated with long-term epilepsy are so “prognostically” benign
Perhaps the most important practical message here is that tumors associated with long-term epilepsy should be removed early, for at least two reasons: (i) likelihood of seizure cure is high (especially when history of epilepsy has been short) and (ii) there is risk, albeit rare, of malignant progression.
References
1. e.g. Fried I, Kim JH, Spencer DD. Limbic and neocortical gliomas associated with intractable seizures: A distinct clinicopathological group. Neurosurgery 1994; 34; 815-23, Zentner J, Hufnagel A, Wolf HK et al, Surgical treatment of neoplasms associated with medically intractable epilepsy. Neurosurgery 1997; 41; 378-86 and Khajavi K, Comair YG, Wyllie E et al. Surgical management of pediatric tumor-associated epilepsy. J Child Neurol 1999; 14; 15-25
2. Piepmeier JM and Christopher S, Low-grade gliomas: introduction and overview. J Neurooncol 1997; 34; 1-3