The etiology of tumor-related seizures (TRS) is reviewed from the Karolinska Institute, Stockholm, Sweden, and University of Pennsylvania, Philadelphia. Multiple causes are considered, involving host and tumor factors. Morphological changes (aberrant neuronal migration, alterations in glial gap-junction coupling), alkaline peritumoral pH, and ion level and amino acid changes (abnormal glutaminergic transmission) in peritumoral brain tissue are probable factors in TRS pathophysiology. Several alterations in enzymatic pathways (eg. lactate dehydrogenase, glutamine synthetase) are observed in epileptic and neoplastic tissues. Cytokines, and tumor necrosis factor in particular, have neuromodulatory effects, and are rapidly induced in glial cells following seizures.

The efficacy of antiepileptic drugs (AED) in TRS is poor, and prophylactic use of AEDs in TRS is not generally recommended. TRS mechanisms (morphological changes, altered receptor patterns, and induction of cytokines) are not influenced by most AEDs. An antineoplastic effect of valproic acid (VPA) is under investigation. Overcoming drug-resistance protein activity (glycoprotein P) may improve response of TRS to AEDs. [1]

COMMENT. The records of 291 consecutive children treated for intracranial tumor at the Mayo Clinic from 1950-1959 were analyzed with particular attention to those with seizures [2]. Seizures occurred in 17% of the total group - in 25% of patients with supratentorial tumors and in 12% of those with infratentorial tumors. Seizures were the initial symptom in 15% with supratentorial and 1% with infratentorial tumors. Average age at onset of tumor-related seizures was 4.9 years. Diagnosis of supratentorial tumors was delayed for an average of 2 years after the initial seizure, whereas infratentorial tumors were diagnosed within 3 months of the seizure onset. Seizures were more common with slowly growing astrocytomas (67% incidence) than with grades 3 and 4 gliomas (10%). Increased intracranial pressure was present with the first seizure in 79% of infratentorial tumors compared to only 20% of supratentorial tumors.

In a study of 560 patients with supratentorial brain tumor at Walton Hospital, Liverpool, UK, a seizure was the first symptom in 164 (30%) [3]. Patients presenting with epilepsy were diagnosed late (mean, 28 months cf 4 months with other symptoms) but had a longer survival (37 months) than those with other symptoms (6 months survival). They were more likely to have a normal neurologic exam and a low-grade tumor. Increasing age at tumor diagnosis, focal neurologic signs, an enhancing CT lesion, surgical biopsy, and male sex were significant independent variables adversely affecting prognosis. Primary IC tumors presenting with epilepsy were relatively benign. They were less likely to receive radiotherapy or biopsy, but more likely to undergo resective surgery. Early resective surgery or radiotherapy were of no benefit. Seizures were refractory to AEDs, only 11 of 164 patients achieving a 1 year remission. The control of tumor-related epilepsy poses a special problem, requiring more specific AEDs. (See Progress in Pediatric Neurology II, PNB Publ, 1994;pp344-345).

Progressive myoclonus in a 22-month-old boy with a deep cerebellar ganglioglioma is reported from the University of Rochester, NY. [4]. The authors theorize that myoclonus resulted from abnormal paroxysmal output from cerebellar nuclei, and was not a case of “cerebellar epilepsy.”

The impact of epilepsy and AED treatment on cognitive functioning was studied in 156 patients with low-grade gliomas [5]. Of 86% with epilepsy, 50% of those on AEDs were seizure-free. Compared to healthy controls, glioma patients had significant reductions in psychomotor function, attention, memory, and quality of life. Cognitive dysfunction was attributed to adverse effects of AEDs, whereas decline in quality of life was ascribed to incomplete seizure control.