Epilepsy is defined as a chronic neurological disorder that can affect individuals of all age groups. It is characterised by recurrent seizures, with the occurrence of two or more seizures defining epilepsy. These seizures manifest as involuntary movements of either one part or the entire body to varying degrees, collectively referred to as convulsions.¹

Within the field of neurology, specific types of epileptic seizures are classified based on the site of initiation within the brain. One such type is temporal lobe epilepsy (TLE), a brain disorder that triggers epileptic seizures originating from the temporal lobe. It is the most prevalent form of focal seizures - also known as partial or localised seizures, primarily affecting only one hemisphere of the brain.²

Introduction

Epileptic disorders can be categorised based on several factors, including the location of the onset of epileptic symptoms in the brain, the patient’s level of consciousness, and the presence or absence of motor symptoms. The recent classification of seizures identifies three major groups:³

1.  Focal onset: these seizures originate in one side of the brain and can further be divided into focal onset aware seizures, where the individual remains conscious, and focal onset impaired awareness seizures, where the person experiences confused or altered awareness.
2. Generalised onset: these seizures affect both sides of the brain and encompass various types, such as tonic-clonic and absence seizures.
3. Unknown onset: these seizures have an undetermined starting point and might be diagnosed retrospectively.

While coping with epileptic seizures poses significant challenges, this classification system enhances precision in guiding professionals toward suitable treatments in each case.

Epidemiologic studies indicate that TLE is the most common epileptic disorder, affecting approximately fifty million people worldwide.² There is no clear sex-based predisposition for TLE thus far due to study limitations. However, people assigned female at birth (AFAB) may experience catamenial seizures, due to the fluctuating female sex hormones during menstrual cycles, which may have proconvulsant or anticonvulsant properties.^4­­­­

The objective of this paper is to comprehensively review the anatomy, aetiology, symptoms, and treatment options for TLE. By doing so, we aim to improve our understanding of this disorder and reduce any associated stigma.

Anatomy of the temporal lobe and epilepsy pathophysiology

To gain a precise understanding of how seizures occur and their association with most symptoms of TLE, a closer look at the anatomy of the temporal lobe is needed. This region of the brain, located near the base of the skull, is subdivided into distinct structures after extensive research into their connection and functions. Among these structures, which make up the limbic system, are the hippocampus, responsible for retrieving declarative memories, and the amygdala, involved in fear and other emotional responses.⁵ Seizures have been strongly linked to these specific regions. TLE is further categorised according to anatomical differences of the epileptic loci:²

• Mesial temporal lobe epilepsy (MTLE), also referred to as limbic epilepsy, is the most common form and primarily involves the hippocampus and amygdala. Hippocampal sclerosis (HS) is often the pathological trigger for these types of seizures.
• Lateral temporal lobe epilepsy (LTLE), is rare and typically arises from genetic anatomical lesions or other structural anomalies, further classified as lesional or non-lesional epilepsy.

The neurological mechanism of a seizure involves an unusual and excessive electrical activity among neurons in certain regions of the brain. Central to this process are chemical messengers known as neurotransmitters, which can either encourage or restrain these electrical signals. When there is an imbalance in these neurotransmitters, characterised by either hyperexcitability or insufficient inhibition, it can cause a neuronal network to fire simultaneously, resulting in a seizure.⁶

Aetiology and risk factors

Understanding where TLE seizures originate is complex and currently relies on speculation after extensive studies on the limbic system. Equally perplexing is its aetiology with several primary causes:

1. Hippocampal sclerosis (HS): HS, a neurodegenerative condition, is prevalent in most MTLE patients. It is related to a certain level of cell loss and gliosis in specific hippocampal regions. Different HS subtypes have been identified, each with distinct prognostic implications for surgical treatment, as drug therapy may not always be effective. Patients who experience seizures in early childhood appear to have a higher likelihood of developing TLE due to HS.²
2. Infections: although less common, certain infections with Herpes simplex encephalitis being the most notable, can lead to TLE.⁷
3. Tumours: specific, relatively rare brain tumours have been associated with TLE, particularly through histopathological analysis in patients with drug-resistant TLE.⁷
4. Traumatic brain injury: post-traumatic epilepsy may develop in individuals who have experienced a traumatic brain injury.²
5. Genetics: Some forms of lateral temporal lobe epilepsy syndromes may have a genetic basis, either through inherited transmission or due to idiopathic genetic mutations.²
6. Cryptogenic temporal lobe epilepsy: this category poses a  significant challenge, requiring further experimental studies to determine its nature and underlying causes.²

Signs and symptoms

Signs and symptoms of TLE may vary depending on the specific type and location of onset of seizures within the temporal lobe. They may include:

1. Focal aware seizures:  patients are conscious and seem to recall this ictal phase (the phase during the seizure). The initial symptoms that constitute the aura phase, include:^2,8
   • Autonomic symptoms with patients experiencing a rising unpleasant sensation from the stomach.
   • Sensory changes like alterations in taste, smell, or visual perceptions, including delusions and hallucinations.
   • Cognitive symptoms such as déjà vu, memory impairment, difficulty speaking (dysphasia)
   • Emotional changes like fear or anxiety.

2. Focal impaired awareness seizures: patients may arrive in this state by gradually losing consciousness. They typically have no recollection of this state. Symptoms include:^2,8
   • A blank stare, dilated pupils, automatic mouth movements like chewing and swallowing, as well as abnormal limb postures (dystonic posturing).
   • Common postictal symptoms (after the seizure) include dysphasia, aphasia and amnesia when the cognitive unit of the temporal lobe is involved.
   • Occasionally, focal seizures may spread to both hemispheres and result in tonic-clonic convulsions.

Diagnosis

Diagnosing TLE involves clinical data analysis and patient history, along with the use of diagnostic tools such as electroencephalography (EEG), video-EEG and magnetoencephalography (MEG), which capture variant waveforms during interictal periods (between seizures) or actual seizures.²

Neuroimaging techniques, including magnetic resonance imaging (MRI), interictal positron emission tomography (PET), and ictal single-photon emission tomography (SPECT), are pivotal for identifying various anatomical aberrancies including tumours, HS and vascular anomalies. Advanced neuroimaging and expert evaluation may be necessary due to challenges in interpreting the results.⁷

The principal goal of diagnosis is to accurately pinpoint the exact epileptogenic region in the temporal lobe and distinguish seizure-free zones before surgery for optimal outcomes.⁷ Early diagnosis and treatment aid in limiting the potential neurocognitive decline in TLE patients.

Treatment and management

Treatment of TLE aims to reduce the frequency of seizures and implicates pharmacological management with anti-seizure medications (ASMs). These drugs, however, have been correlated with numerous adverse effects including hepatotoxicity.² About one-third of TLE patients may develop refractory epilepsy, meaning that their condition shows drug resistance. In this case, ASMs can no longer control the frequency or severity of seizures, leading to the need for surgical intervention to remove locations of epileptogenic focus in the temporal lobe.²

For patients unsuitable or unwilling to undergo surgery, vagus nerve stimulation is an alternative treatment method.⁷

Psychosocial impact and current research

Patients with TLE should seek assessment as soon as possible to achieve the best possible outcomes through personalised interventions. It is important to note that post-surgical outcomes may have various effects on patients’ normal cognitive, perceptual and especially emotional functions. They may present depression, anxiety, and memory impairment, among other issues. Therefore, it is essential to provide extra care and conduct detailed tests to genuinely improve their quality of life.⁹

Promising innovative research and therapies are continually emerging to enhance the quality of life of TLE patients. One recent preventive approach explores the use of electrodes that can predict and prevent seizures even thirty minutes before their onset, by analysing the preictal (before seizure onset) pathologic brain activities.¹⁰

Another novel therapy for TLE is deep brain stimulation, which introduces electrical stimulation to epileptic foci through electrodes.¹¹ Additionally, ongoing research is focused on developing novel ASMs, treatment strategies with different targets, and providing precise guidance to healthcare providers.

Summary

In summary, TLE remains enigmatic, despite being one of the most common forms of epilepsy. It necessitates further exploration and understanding, particularly focusing on the temporal lobe, which plays a crucial role in memory and emotions. Extensive research is required to unveil its distinct characteristics and gain a comprehensive grasp of the wide range of symptoms associated with TLE, including autonomic, cognitive, emotional, and consciousness-related issues. Effectively addressing these challenges is vitalfor improving outcomes post-intervention.

TLE can have profound neurological and psychosocial impact on patients, leading to cognitive and emotional difficulties. It is imperative to support and encourage patients to openly discuss their experiences and emotions, not only to have a clearer image of ictal symptomatology but also to minimise the stigma associated with cognitive decline.

Early diagnosis and ongoing research are also essential. Healthcare professionals need access to the latest information to be able to discuss and guide TLE patients through their personalised treatment options. These efforts contribute to a more promising future and an improved quality of life for individuals living with TLE.