A Course Project: Review on Mesial Temporal Lobe Epilepsy
This review article explores mesial temporal lobe epilepsy (MTLE), a common focal epilepsy. It begins by providing an overview of the disorder in terms of risk factors and affected populations. Then an outline of different symptoms in the four stages of seizure is summarized. Based on the outline, the article also addresses the neurological sequelae related to abnormal cell growth and dentate signal filtering malfunction in MTLE and explains the epileptogenesis in terms of its repeated occurrence. Last but not least, it introduces the role of respiratory brain pulse mechanisms in cerebrospinal fluid homeostasis and their possible disruption in more general epileptic populations.
Epilepsy?
MTLE?
Epilepsy is a neurological disorder characterized by recurrent, unprovoked seizures that affects 50 million people worldwide each year (Kananen et al., 2020). Its subtype, mesial temporal lobe epilepsy (MTLE), is the most common focal epilepsy syndrome. The age of seizure onset for MTLE is at an average of 10.9 years old (Vinti et al., 2021). MTLE is categorized into localized complex partial seizure, which indicates that patients are usually unconscious during seizure. Common seizure manifestations of MTLE include epigastric aura (nausea or discomfort in the abdominal region), dystonic posturing (muscle contraction that causes sustained abnormal limb positioning), and oral automatisms (uncontrolled lip smacking, chewing, swallowing). MTLE is also associated with anxiety, depression, and interictal dysphoria (depressive mood symptoms associated with epilepsy). Structurally, abnormalities in mesial temporal sclerosis (MTS, also refers to hippocampal sclerosis) occur most commonly in TLE patients.
MTLE is considered to be an acquired condition, where it arises from previous normal brain structures such as hippocampus, amygdala, and parahippocampal gyrus. Due to its heterogeneous and comorbid nature, the cause of MTLE varies in different cases, remaining unclear. Mesial temporal sclerosis, prolonged febrile seizures, head injuries, viral infection, autoimmune disease, etc., can all potentially induce MTLE (What Is Mesial Temporal Sclerosis | MTS Symptoms, n.d.). It may also have connections with dysfunction in blood-brain-barrier and imbalanced excitation and inhibition (Rüber et al., 2018).
Conceptually, MTLE can be decomposed into seizure and frequency of episodes. Epileptic seizure consists of four stages, including prodrome, aura, ictal, and postictal. Ictal phase is when the actual seizure happens. This article first reviews the incidence of MTLE, then discusses the presentation and potential mechanisms following the conceptual framework mentioned above.
How to identify MTLE patients?
MTLE has no age or sexual predominance (Miller & Goodkin, 2014). Patients usually have normal perinatal history, normal development throughout childhood, and are cognitively intact. However, any forms of damage to the mesial temporal regions of the brain may increase risk to the onset of MTLE. Hippocampal injuries are observed in 9.7% of MTLE patients (Nayak, 2023), and a childhood history of febrile seizure may increase occurrence of MTLE in later life.
MTLE patients also show atypical EEG patterns during the ictal phase of epilepsy. To be more specific, during and between seizures, periods of intermittent slowing in the temporal lobe and delayed rhythmic spread to neighboring brain regions may manifest (Nayak, 2023).
In a case study on surgical intervention for MTLE, the epileptic patient recruited had febrile seizure as a baby and showed rhythmic slowness in the right temporal region (Panday et al., 2019), which is quite typical for epilepsy.
Respiration related disorders such as sleep apnea may also have a link to MTLE. Study has shown that the cerebrospinal fluid homeostasis that is driven by respiratory brain pulse mechanism may be altered in epileptic patients, suggesting a dysfunctioning glymphatic brain clearing system (Kananen et al., 2020).
Presentation and Neurological Sequelae of MTLE
The term epileptogenesis is defined as the period between initial insult and recurrent seizures where there are no overt seizures happening. It shows the brain’s plasticity in between an incident and the onset of the first seizure. Several studies also supported that epilepsy may be progressive (Cole, 2000) and evolving over the life span (Scharfman, 2007) in some cases. Even after the ongoing seizures start, the brain still shows a certain degree of plasticity. For MTLE, recurrent seizures may cause progressive damage to affected brain regions. Therefore, investigating MTLE from a progressive framework may answer questions regarding its developing process.
1. Single Episode of Epileptic Seizure
MTLE seizure usually lasts from 30 seconds to two minutes. Prior to the seizure, patients usually experience a prodrome that may include but not limited to mood changes, abdominal sensitivity, strange odor or taste. The timeframe of this period is longer compared to the actual seizure, but may range from hours to days due to individual differences. As time progresses to minutes before seizure, patients may experience automatisms such as lip smacking, swallowing, repetitive body movements, and sudden laughter episodes (Mesial Temporal Lobe Epilepsy, n.d.). During seizure in the ictal phase, patients may become unconscious and show an obvious cessation or alteration of prodromes and aura behaviors such as oral automatisms, staring, and repetitive picking of hands. These symptoms can leave patients with oral muscle fatigue or biting of the tongue. The patient may also feel a rising sensation in mesial temporal regions. After seizure, patients may experience postictal cough, uncontrolled laughter (gelastic), loud vocalization, and ictal speech arrest due to affected temporal lobe and surrounding regions (Miller & Goodkin, 2014). Patients may also go into a period of postictal confusion after the episode. In rare cases, episodes may generalize into more severe seizures (Nayak, 2023).
One approach to explain these symptoms is the hyperexcitation of the atypically interconnected neural networks in the temporal area. In TLE patients, the axons of certain cells may overextend into deeper brain layers where there are massive granule cells’ dendrites. Granule cells presented in dentate gyrus or other related regions may be interconnected into a grand synchronizing network and can increase recurrent excitatory circuitry (Scharfman, 2007). The reorganized neuronal connections may provide the physiology for repetitive oral and motor behaviors in seizures to happen. The dentate gate phenomenon takes this explanation further. Dentate gyrus filters signals from the entorhinal cortex before it goes into hippocampal CA3 area, and dentate granule cells have a function in modulation of cognition. Therefore, developed dentate gate dysfunction may contribute to the disturbance of normal cell signals, leading to atypical behavior and mood changes in MTLE.
2. Repeated Occurrence of Seizure in MTLE
Epilepsy is defined as the occurrence of at least two unprovoked seizures within a minimum 24-hour gap between them (“Epilepsy,” 2021). MTLE patients experience 3 to 4 complex partial seizures per month on average. Therefore, it is meaningful to understand the repetitive pattern of epileptic episodes for prevention of ongoing seizures.
Study on rodent models found that onset of seizures in early life may increase possibility and severity for later seizures (Cole, 2000). Patients with altered brain state of excitability prone to develop seizures during ordinary activities such as circadian changes of hormones or sleep-wake cycles (Scharfman, 2007). There is also evidence for progressive neuronal loss in TLE. Cell loss in the mesial temporal lobe can follow acute, prolonged seizure activity. Though TLE may be associated with the onset of recurrent seizure, the duration of epilepsy may not be an influencing factor (Tasch et al., 1999).
3. Additional Perspective for Epilepsy in General
Another potential mechanism and indicator for epilepsy is the malfunction of the glymphatic brain clearing system where the blood-brain-barrier and pneumotaxic center (respiration-related) are involved. Respiration is suggested to be a driving force for cerebrospinal fluid convection and may be coupled with limbic and cortical regions. Evidence shows that increased power of respiratory pulsation is observed in epilepsies, indicating a potential link (Kananen et al., 2020). Meanwhile, the blood-brain-barrier protects and maintains the homeostasis of the brain. Its outer layer also functions as a clearance system that filters out damaging ions and proteins. Thus, failure of glymphatic cerebrospinal fluid clearance of blood-brain-barrier can predispose the brain to epilepsy and seizure.
To Conclude
The article has discussed the occurrence, symptoms, and potential underlying systematic atypicality of MTLE and epilepsy in general. As epilepsy has mutual connections with many environmental and anatomical factors, it is hard to reduce its cause to a single mechanism. Misconnection between cells, malfunction in signal filtering gate, imbalance excitation, and ineffective clearance of cerebrospinal fluid may play roles during epilepsy episodes. Identifying these key mechanisms can potentially serve as targets in seizure control and therapeutic intervention. However, due to the comorbidity of MTLE and varied individual differences, diagnosis and treatment should be evaluated on a case-by-case basis.
References
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