Causes of Temporal Lobe Epilepsy
Temporal lobe epilepsy results from both structural and genetic etiologies, with mesial temporal sclerosis (hippocampal sclerosis) being the most common identifiable cause in adults, while malformations of cortical development predominate in children with medically refractory disease. 1, 2
Primary Structural Causes in Adults
Mesial temporal sclerosis (hippocampal sclerosis) is the single most frequent cause of temporal lobe epilepsy in adults, accounting for the majority of cases that come to surgical evaluation. 1, 2, 3 This pathological substrate represents the most common epileptogenic lesion encountered in epilepsy patients overall. 3
Additional acquired structural causes include:
- Stroke and cerebral infarction represent common acquired causes of focal temporal seizures in adults 1
- Low-grade epilepsy-associated brain tumors (LEAT) can originate in temporal structures and cause seizures 4, 1
- Vascular malformations localized to temporal regions 1
- Infectious lesions including inflammatory scars from prior infections 1, 5
- Traumatic brain injury with late sequelae affecting temporal structures 5
Developmental and Congenital Causes
Malformations of cortical development (MCD) represent the most common cause of medically refractory focal epilepsy in children, with temporal lobe involvement being frequent. 4, 1
Specific developmental abnormalities include:
- Focal cortical dysplasia (FCD) is the most frequent MCD subtype, presenting as focal irregularity of cortical morphology and thickness 4, 1
- Heterotopic white matter neurons and cerebral microdysgenesis in lateral temporal structures, found in a substantial proportion of surgical specimens 6
- Polymicrogyria (PMG) characterized by excessive numbers of abnormally small cerebral gyri with cortical overfolding 4, 1
- Hemimegalencephaly when involving temporal regions 4, 1
Perinatal and Birth-Related Causes
- Birth-related lesions including perinatal stroke or hemorrhages are important causes in pediatric temporal lobe epilepsy 4, 1
- Hypoxic-ischemic injury can affect temporal structures, though this is more commonly associated with neonatal seizures broadly 1
Genetic and Idiopathic Forms
Growing evidence demonstrates important genetic influences in temporal lobe epilepsy, particularly in familial and non-lesional cases. 7 While the molecular mechanisms remain incompletely understood, genetic factors play a more significant role than previously recognized. 7
- Idiopathic temporal lobe epilepsy occurs when genetically transmitted conditions produce epilepsy without structural lesions or neurological deficits 8
- Familial temporal lobe epilepsy has been increasingly described over the past two decades 7
Cryptogenic Cases
- Cryptogenic temporal lobe epilepsy represents cases where no etiology can be determined despite thorough evaluation 8
- These cases remain a major clinical challenge requiring further research to identify underlying mechanisms 8
Pathophysiological Considerations
The epileptogenic substrate often involves alterations in temporal lobe circuitry and connectivity, not just isolated lesions. 5
- Malformations of normal hippocampal circuitry and foci of microdysgenesis may result from insults during critical periods of brain development, predisposing to increased excitability and seizurogenesis 5
- Gliosis in lateral temporal structures is a common finding, with GFAP-positive astrocytes often present throughout the temporal lobe in surgical specimens 6
- Both enhanced inhibition and enhanced excitation contribute to hypersynchronous neuronal discharges generating spontaneous seizures 3
Clinical Implications for Diagnosis
The specific cause directly impacts surgical planning and prognosis, making accurate etiological diagnosis essential:
- Hippocampal sclerosis shows excellent surgical outcomes with appropriate resection 2
- Concordance between MRI findings, EEG localization, and functional imaging (PET/SPECT) predicts better surgical outcomes regardless of specific etiology 2
- Complete resection of the epileptogenic zone is critical for optimal seizure control across all structural causes 2