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Temporal lobe epilepsy (TLE) is a chronic disorder of the
nervous system In biology, the nervous system is the highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes th ...
which is characterized by recurrent, unprovoked
focal seizure Focal seizures (also called partial seizures and localized seizures) are seizures which affect initially only one hemisphere of the brain. The brain is divided into two hemispheres, each consisting of four lobes – the frontal, temporal, parie ...
s that originate in the
temporal lobe The temporal lobe is one of the four Lobes of the brain, major lobes of the cerebral cortex in the brain of mammals. The temporal lobe is located beneath the lateral fissure on both cerebral hemispheres of the mammalian brain. The temporal lobe ...
of the
brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...
and last about one or two minutes. TLE is the most common form of
epilepsy Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical ...
with
focal seizure Focal seizures (also called partial seizures and localized seizures) are seizures which affect initially only one hemisphere of the brain. The brain is divided into two hemispheres, each consisting of four lobes – the frontal, temporal, parie ...
s. A focal seizure in the temporal lobe may spread to other areas in the brain when it may become a ''focal to bilateral seizure''. TLE is diagnosed by taking a
medical history The medical history, case history, or anamnesis (from Greek: ἀνά, ''aná'', "open", and μνήσις, ''mnesis'', "memory") of a patient is information gained by a physician by asking specific questions, either to the patient or to other peo ...
,
blood test A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a hypodermic needle, or via fingerprick. Multiple tests for specific blood components, such as a glucose test or a cholester ...
s, and
brain imaging Neuroimaging is the use of quantitative (computational) techniques to study the neuroanatomy, structure and function of the central nervous system, developed as an objective way of scientifically studying the healthy human brain in a non-invasive ...
. It can have a number of causes such as
head injury A head injury is any injury that results in trauma to the skull or brain. The terms ''traumatic brain injury'' and ''head injury'' are often used interchangeably in the medical literature. Because head injuries cover such a broad scope of inju ...
,
stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
, brain infections, structural
lesions A lesion is any damage or abnormal change in the tissue of an organism, usually caused by disease or trauma. ''Lesion'' is derived from the Latin "injury". Lesions may occur in plants as well as animals. Types There is no designated classifi ...
in the brain,
brain tumor A brain tumor occurs when abnormal cells form within the brain. There are two main types of tumors: malignant tumors and benign (non-cancerous) tumors. These can be further classified as primary tumors, which start within the brain, and seconda ...
s, or it can be of ''unknown onset''. The first line of treatment is through
anticonvulsants Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of b ...
. Surgery may be an option, especially when there is an observable abnormality in the brain. Another treatment option is electrical stimulation of the brain through an implanted device called the
vagus nerve stimulator Vagus nerve stimulation (VNS) is a medical treatment that involves delivering electrical impulses to the vagus nerve. It is used as an add-on treatment for certain types of intractable epilepsy and treatment-resistant depression. Medical use VNS ...
(VNS).


Types

Over forty types of epilepsy are recognized and these are divided into two main groups:
focal seizure Focal seizures (also called partial seizures and localized seizures) are seizures which affect initially only one hemisphere of the brain. The brain is divided into two hemispheres, each consisting of four lobes – the frontal, temporal, parie ...
s and
generalized seizures Generalized epilepsy is a form of epilepsy characterised by generalised seizures with no apparent cause. Generalized seizures, as opposed to focal seizures, are a type of seizure that impairs consciousness and distorts the electrical activity of ...
.
Focal seizure Focal seizures (also called partial seizures and localized seizures) are seizures which affect initially only one hemisphere of the brain. The brain is divided into two hemispheres, each consisting of four lobes – the frontal, temporal, parie ...
s account for approximately sixty percent of all adult cases. Temporal lobe epilepsy (TLE) is the single most common form of focal seizure. The
International League Against Epilepsy The International League Against Epilepsy was started in 1909. Its goal is to improve the lives of people with epilepsy through research. They run the medical journals ''Epilepsia'', ''Epilepsia Open'', and ''Epileptic Disorders ''Epileptic Disor ...
(ILAE) recognizes two main types of temporal lobe epilepsy: mesial temporal lobe epilepsy (MTLE), arising in the
hippocampus The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, a ...
, the
parahippocampal gyrus The parahippocampal gyrus (or hippocampal gyrus') is a grey matter cortical region of the brain that surrounds the hippocampus and is part of the limbic system. The region plays an important role in memory encoding and retrieval. It has been inv ...
and the
amygdala The amygdala (; plural: amygdalae or amygdalas; also '; Latin from Greek, , ', 'almond', 'tonsil') is one of two almond-shaped clusters of nuclei located deep and medially within the temporal lobes of the brain's cerebrum in complex verteb ...
which are located in the inner ( medial) aspect of the temporal lobe, and lateral temporal lobe epilepsy (LTLE), the rarer type, arising in the
neocortex The neocortex, also called the neopallium, isocortex, or the six-layered cortex, is a set of layers of the mammalian cerebral cortex involved in higher-order brain functions such as sensory perception, cognition, generation of motor commands, sp ...
at the outer (
lateral Lateral is a geometric term of location which may refer to: Healthcare *Lateral (anatomy), an anatomical direction *Lateral cricoarytenoid muscle *Lateral release (surgery), a surgical procedure on the side of a kneecap Phonetics *Lateral cons ...
) surface of the temporal lobe. The seizures of LTLE are characterized by auditory or visual features.
Autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
lateral temporal lobe epilepsy (ADLTLE) is a rare hereditary condition, often associated with mutations in the
LGI1 Leucine-rich, glioma inactivated 1, also known as LGI1, is a protein which in humans is encoded by the ''LGI1'' gene. It may be a metastasis suppressor. Function The leucine-rich glioma inactivated -1 gene is rearranged as a result of translo ...
gene.


Signs and symptoms

When a seizure begins in the temporal lobe, its effects depend on the precise location of its point of origin, its ''locus''. In 1981, the ILAE recognized three types of seizures occurring in temporal lobe epilepsy. The classification was based on
EEG Electroencephalography (EEG) is a method to record an electrogram of the spontaneous electrical activity of the brain. The biosignals detected by EEG have been shown to represent the postsynaptic potentials of pyramidal neurons in the neocortex ...
findings. However, as of 2017 the general classification of seizures has been revised. The newer classification uses three key features: where the seizures begin, the level of awareness during a seizure, and other features.


Focal seizures

Focal seizure Focal seizures (also called partial seizures and localized seizures) are seizures which affect initially only one hemisphere of the brain. The brain is divided into two hemispheres, each consisting of four lobes – the frontal, temporal, parie ...
s in the temporal lobe involve small areas of the lobe such as the
amygdala The amygdala (; plural: amygdalae or amygdalas; also '; Latin from Greek, , ', 'almond', 'tonsil') is one of two almond-shaped clusters of nuclei located deep and medially within the temporal lobes of the brain's cerebrum in complex verteb ...
and
hippocampus The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, a ...
. The newer classification gives two types of ''focal onset seizures'', as ''focal aware'' and ''focal impaired awareness''.


Focal aware seizures

''Focal aware'' means that the level of consciousness is not altered during the seizure. In temporal lobe epilepsy, a focal seizure usually causes abnormal sensations only. Often, the patient cannot describe the sensations. These may be: * Sensations such as
déjà vu ''Déjà vu'' ( , ; "already seen") is a French loanword for the phenomenon of feeling as though one has lived through the present situation before.Schnider, Armin. (2008). ''The Confabulating Mind: How the Brain Creates Reality''. Oxford Univer ...
(a feeling of familiarity),
jamais vu In psychology, ''jamais vu'' ( , , ), a French loanword meaning "never seen", is the phenomenon of experiencing a situation that one recognizes in some fashion, but that nonetheless seems novel and unfamiliar. Overview Jamais vu is often de ...
(a feeling of unfamiliarity) *
Amnesia Amnesia is a deficit in memory caused by brain damage or disease,Gazzaniga, M., Ivry, R., & Mangun, G. (2009) Cognitive Neuroscience: The biology of the mind. New York: W.W. Norton & Company. but it can also be caused temporarily by the use ...
of a single memory or set of memories * A sudden sense of unprovoked fear and anxiety * Nausea * Auditory, visual, olfactory, gustatory, or tactile
hallucination A hallucination is a perception in the absence of an external stimulus that has the qualities of a real perception. Hallucinations are vivid, substantial, and are perceived to be located in external objective space. Hallucination is a combinatio ...
s; olfactory hallucinations often seem indescribable to patients beyond "pleasant" or "unpleasant" * Visual distortions such as
macropsia Macropsia is a neurological condition affecting human visual perception, in which objects within an affected section of the visual field appear larger than normal, causing the person to feel smaller than they actually are. Macropsia, along with its ...
and
micropsia Micropsia is a condition affecting human visual perception in which objects are perceived to be smaller than they actually are. Micropsia can be caused by optical factors (such as wearing glasses), by distortion of images in the eye (such as optica ...
*
Dissociation Dissociation, in the wide sense of the word, is an act of disuniting or separating a complex object into parts. Dissociation may also refer to: * Dissociation (chemistry), general process in which molecules or ionic compounds (complexes, or salts ...
or
derealisation Derealization is an alteration in the perception of the external world, causing those with the condition to perceive it as unreal, distant, distorted or falsified. Other symptoms include feeling as if one's environment is lacking in spontaneity, ...
*
Synesthesia Synesthesia (American English) or synaesthesia (British English) is a perceptual phenomenon in which stimulation of one sensory or cognitive pathway leads to involuntary experiences in a second sensory or cognitive pathway. People who re ...
(stimulation of one sense experienced in a second sense) * Dysphoric or euphoric feelings, fear, anger, and other emotions Focal aware seizures are often called " auras" when they serve as a warning sign of a subsequent seizure. Regardless, an ''aura'' is actually a seizure itself, and such a focal seizure may or may not progress to a focal impaired awareness seizure. People who experience only focal aware seizures may not recognize what they are, nor seek medical care.


Focal impaired awareness seizures

Focal impaired awareness seizures are seizures which impair consciousness to some extent: they alter the person's ability to interact normally with their environment. They usually begin with a focal aware seizure, then spread to a larger portion of the temporal lobe, resulting in impaired consciousness. They may include autonomic and psychic features present in focal aware seizures. Signs may include: * Motionless staring * Automatic movements of the hands or mouth * Confusion and disorientation * Altered ability to respond to others, unusual speech * Transient
aphasia Aphasia is an inability to comprehend or formulate language because of damage to specific brain regions. The major causes are stroke and head trauma; prevalence is hard to determine but aphasia due to stroke is estimated to be 0.1–0.4% in t ...
(losing ability to speak, read, or comprehend spoken word) These seizures tend to have a warning or aura before they occur, and when they occur they generally tend to last only 1–2 minutes. It is not uncommon for an individual to be tired or confused for up to 15 minutes after a seizure has occurred, although postictal confusion can last for hours or even days. Though they may not seem harmful, due to the fact that the individual does not normally seize, they can be extremely harmful if the individual is left alone around dangerous objects or in situations requiring acute awareness, such as sterring a vehicle or operating machinery. With this type, some people do not even realize they are having a seizure and most of the time their memory from right before to after the seizure is wiped. First-aid is only required if there has been an injury or if this is the first time a person has had a seizure.


Focal to bilateral seizures or generalized seizures

Seizures which begin in the temporal lobe, and then spread to involve both sides of the brain are termed ''focal to bilateral''. Where both sides of the brain or the whole brain are involved from the onset, these seizures are known as
generalized seizure Generalized epilepsy is a form of epilepsy characterised by generalised seizures with no apparent cause. Generalized seizures, as opposed to focal seizures, are a type of seizure that impairs consciousness and distorts the electrical activity of ...
s and may be tonic clonic. The arms, trunk, and legs stiffen (the tonic phase), in either a flexed or extended position, and then jerk (the clonic phase). These were previously known as ''grand mal'' seizures. The word ''grand mal'' comes from the French term, meaning ''major affliction.''


Postictal period

There is some period of recovery in which neurological function is altered after each of these seizure types. This is the ''
postictal state The postictal state is the altered state of consciousness after an epileptic seizure. It usually lasts between 5 and 30 minutes, but sometimes longer in the case of larger or more severe seizures, and is characterized by drowsiness, confusion, na ...
''. The degree and length of postictal impairment directly correlates with the severity of the seizure type. Focal aware seizures often last less than sixty seconds; focal with impaired awareness seizures may last up to two minutes; and generalized tonic clonic seizures may last up to three minutes. The postictal state in seizures other than ''focal aware'' may last much longer than the seizure itself. Because a major function of the temporal lobe is short-term memory, a focal with impaired awareness seizure, and a focal to bilateral seizure can cause amnesia for the period of the seizure, meaning that the seizure may not be remembered.


Complications


Depression

Individuals with temporal lobe epilepsy have a higher prevalence of depression than the general population. Although the psychosocial impacts of epilepsy may be causative, there are also links in the
phenomenology Phenomenology may refer to: Art * Phenomenology (architecture), based on the experience of building materials and their sensory properties Philosophy * Phenomenology (philosophy), a branch of philosophy which studies subjective experiences and a ...
and
neurobiology Neuroscience is the scientific study of the nervous system (the brain, spinal cord, and peripheral nervous system), its functions and disorders. It is a multidisciplinary science that combines physiology, anatomy, molecular biology, development ...
of TLE and depression.


Memory

The temporal lobe and particularly the
hippocampus The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, a ...
play an important role in memory processing.
Declarative memory Explicit memory (or declarative memory) is one of the two main types of long-term human memory, the other of which is implicit memory. Explicit memory is the conscious, intentional recollection of factual information, previous experiences, and con ...
(memories which can be consciously recalled) is formed in the area of the hippocampus called the ''
dentate gyrus The dentate gyrus (DG) is part of the hippocampal formation in the temporal lobe of the brain, which also includes the hippocampus and the subiculum. The dentate gyrus is part of the hippocampal trisynaptic circuit and is thought to contribute ...
''. Temporal lobe epilepsy is associated with memory disorders and loss of memory.
Animal models A model organism (often shortened to model) is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the working ...
and clinical studies show that memory loss correlates with temporal lobe
neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
al loss in temporal lobe epilepsy.
Verbal memory Verbal memory is a term used in cognitive psychology which refers to memory of words and other abstractions involving language. Verbal encoding Verbal encoding refers to the interpretation of verbal stimuli. Verbal encoding appears to be strongly ...
deficit correlates with pyramidal cell loss in TLE. This is more so on the left in verbal memory loss. Neuronal loss on the right is more prominent in non-verbal ( visuospatial memory loss).


Childhood onset

After childhood onset, one third will "grow out" of TLE, finding a lasting remission up to an average of 20 years. The finding of a lesion such as
hippocampal sclerosis Hippocampal sclerosis (HS) or mesial temporal sclerosis (MTS) is a neuropathological condition with severe neuronal cell loss and gliosis in the hippocampus, specifically in the CA-1 (Cornu Ammonis area 1) and subiculum of the hippocampus. It w ...
(a scar in the hippocampus), tumour, or
dysplasia Dysplasia is any of various types of abnormal growth or development of cells (microscopic scale) or organs (macroscopic scale), and the abnormal histology or anatomical structure(s) resulting from such growth. Dysplasias on a mainly microscopic ...
, on
magnetic resonance imaging Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio wave ...
(MRI) predicts the intractability of seizures.


Personality

The effect of temporal lobe epilepsy on personality is a historical observation dating to the 1800s. Personality and behavioural change in temporal lobe epilepsy is seen as a chronic condition when it persists for more than three months.
Geschwind syndrome Geschwind syndrome, also known as Gastaut-Geschwind, is a group of behavioral phenomena evident in some people with temporal lobe epilepsy. It is named for one of the first individuals to categorize the symptoms, Norman Geschwind, who published prol ...
is a set of behavioural phenomena seen in some people with TLE. Documented by
Norman Geschwind Norman Geschwind (January 8, 1926 – November 4, 1984) was a pioneering American Behavioral neurology, behavioral neurologist, best known for his exploration of behavioral neurology through disconnection models based on lesion analysis. Earl ...
, signs include:
hypergraphia Hypergraphia is a behavioral condition characterized by the intense desire to write or draw. Forms of hypergraphia can vary in writing style and content. It is a symptom associated with temporal lobe changes in epilepsy and in Geschwind syndrome ...
(compulsion to write (or draw) excessively),
hyperreligiosity Hyperreligiosity is a psychiatric disturbance in which a person experiences intense religious beliefs or episodes that interfere with normal functioning. Hyperreligiosity generally includes abnormal beliefs and a focus on religious content or eve ...
(intense religious or philosophical experiences or interests), hyposexuality (reduced sexual interest or drive),
circumstantiality Circumstantial speech, also referred to as circumstantiality, is the result of a so-called "non-linear thought pattern" and occurs when the focus of a conversation drifts, but often comes back to the point.''Problem-Based Psychiatry'' by Ben Green 2 ...
(result of a non-linear thought pattern, talks at length about irrelevant and trivial details). The personality changes generally vary by hemisphere. The existence of a "temporal lobe epileptic personality" and of Geschwind syndrome have been disputed and research is inconclusive.


Causes

The causes of TLE include
mesial temporal sclerosis Hippocampal sclerosis (HS) or mesial temporal sclerosis (MTS) is a neuropathological condition with severe neuronal cell loss and gliosis in the hippocampus, specifically in the CA-1 (Cornu Ammonis area 1) and subiculum of the hippocampus. It wa ...
,
traumatic brain injury A traumatic brain injury (TBI), also known as an intracranial injury, is an injury to the brain caused by an external force. TBI can be classified based on severity (ranging from mild traumatic brain injury TBI/concussionto severe traumatic b ...
, brain infections, such as
encephalitis Encephalitis is inflammation of the brain. The severity can be variable with symptoms including reduction or alteration in consciousness, headache, fever, confusion, a stiff neck, and vomiting. Complications may include seizures, hallucinations, ...
and
meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, headache, and neck stiffness. Other symptoms include confusion or ...
, hypoxic brain injury, stroke, cerebral tumours, and genetic syndromes. Temporal lobe epilepsy is not the result of psychiatric illness or fragility of the personality.


Febrile seizures

Although the theory is controversial, there is a link between
febrile seizure A febrile seizure, also known as a fever fit or febrile convulsion, is a seizure associated with an increased body temperature Thermoregulation is the ability of an organism to keep its body temperature within certain boundaries, even whe ...
s (seizures coinciding with episodes of fever in young children) and subsequent temporal lobe epilepsy, at least epidemiologically.


Human herpes virus 6

In the mid-1980s,
human herpesvirus 6 Human herpesvirus 6 (HHV-6) is the common collective name for '' human betaherpesvirus 6A'' (HHV-6A) and '' human betaherpesvirus 6B'' (HHV-6B). These closely related viruses are two of the nine known herpesviruses that have humans as their prim ...
(HHV-6) was suggested as a possible causal link between febrile convulsions and mesial temporal lobe epilepsy. However, although the virus is found in temporal lobe tissue at surgery for TLE, it has not been recognised as a major factor in febrile seizures or TLE.


Reelin

Dispersion of the granule cell layer in the hippocampal
dentate gyrus The dentate gyrus (DG) is part of the hippocampal formation in the temporal lobe of the brain, which also includes the hippocampus and the subiculum. The dentate gyrus is part of the hippocampal trisynaptic circuit and is thought to contribute ...
is occasionally seen in temporal lobe epilepsy and has been linked to the downregulation of
reelin Reelin, encoded by the ''RELN'' gene, is a large secreted extracellular matrix glycoprotein that helps regulate processes of neuronal migration and positioning in the developing brain by controlling cell–cell interactions. Besides this import ...
, a protein that normally keeps the layer compact by containing
neuronal migration The development of the nervous system, or neural development (neurodevelopment), refers to the processes that generate, shape, and reshape the nervous system of animals, from the earliest stages of embryonic development to adulthood. The fiel ...
. It is unknown whether changes in reelin expression play a role in epilepsy.


Pathophysiology


Neuronal loss

In TLE, there is loss of neurons in region CA1 and CA3 of the
hippocampus The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, a ...
.de Lanerolle N. C. and Noebels J. L. (ed.) ''Jasper's basic mechanisms of the epilepsies: histopathology of human epilepsy''. Oxford University Press 2012 chapter 30 . There is also damage to mossy cells and inhibitory
interneuron Interneurons (also called internuncial neurons, relay neurons, association neurons, connector neurons, intermediate neurons or local circuit neurons) are neurons that connect two brain regions, i.e. not direct motor neurons or sensory neurons. I ...
s in the hilar region of the hippocampus (region IV) and to the
granule cells A granule is a large particle or grain. It can refer to: * Granule (cell biology), any of several submicroscopic structures, some with explicable origins, others noted only as cell type-specific features of unknown function ** Azurophilic granul ...
of the
dentate gyrus The dentate gyrus (DG) is part of the hippocampal formation in the temporal lobe of the brain, which also includes the hippocampus and the subiculum. The dentate gyrus is part of the hippocampal trisynaptic circuit and is thought to contribute ...
. In animal models, neuronal loss occurs during seizures but in humans, neuronal loss predates the first seizure and does not necessarily continue with seizure activity. The loss of the GABA-mediated inhibitory interneurons may increase the hyperexcitability of neurons of the hippocampus leading to recurrent seizures. According to the "dormant
basket cell Basket cells are inhibitory GABAergic interneurons of the brain, found throughout different regions of the cortex and cerebellum. Anatomy and physiology Basket cells are multipolar GABAergic interneurons that function to make inhibitory synapses ...
" hypothesis, mossy cells normally excite basket cells which in turn, inhibit granule cells. Loss of mossy cells lowers the threshold of action potentials of the granule cells.


GABA reversal

In certain patients with temporal lobe epilepsy it has been found that the
subiculum The subiculum (Latin for "support") is the most inferior component of the hippocampal formation. It lies between the entorhinal cortex and the CA1 subfield of the hippocampus proper. The subicular complex comprises a set of related structures in ...
could generate epileptic activity. It has been found that GABA reversal potential is depolarising in the subpopulation of the pyramidal cells due to the lack of KCC2 co-transporter. It has been shown that it is theoretically possible to generate seizures in the neural networks due to down-regulation of KCC2, consistent with the chloride measurements during the transition to seizure and KCC2 blockade experiments.


Granule cell dispersion in the dentate gyrus

Granule cell dispersion is a type of developmental migration and a pathological change found in the TLE brain which was first described in 1990. The granule cells of the
dentate gyrus The dentate gyrus (DG) is part of the hippocampal formation in the temporal lobe of the brain, which also includes the hippocampus and the subiculum. The dentate gyrus is part of the hippocampal trisynaptic circuit and is thought to contribute ...
are tightly packed forming a uniform, laminated layer with no monosynaptic connections. This structure provides a filter for the excitability of neurons. In TLE, granule cells are lost, the structure is no longer closely packed and there are changes in the orientation of
dendrite Dendrites (from Greek δένδρον ''déndron'', "tree"), also dendrons, are branched protoplasmic extensions of a nerve cell that propagate the electrochemical stimulation received from other neural cells to the cell body, or soma, of the n ...
s. These changes may or may not be epileptogenic. For instance, if the dendrites of granule cells reconnect, it may be in a way (through the laminar planes) that allows hyperexcitability. However, not all patients have granule cell dispersion.


Aberrant mossy fiber sprouting

Mossy fibers are the
axon An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action po ...
s of
granule cell A granule is a large particle or grain. It can refer to: * Granule (cell biology), any of several submicroscopic structures, some with explicable origins, others noted only as cell type-specific features of unknown function ** Azurophilic granul ...
s. They project into the hilus of the dentate gyrus and
stratum lucidum The stratum lucidum (Latin, 'clear layer') is a thin, clear layer of dead skin cells in the epidermis named for its translucent appearance under a microscope. It is readily visible by light microscopy only in areas of thick skin, which are found ...
in the CA3 region giving inputs to both excitatory and inhibitory neurons. In the TLE brain, where granule cells are damaged or lost, axons, the ''mossy'' fibres, 'sprout' in order to reconnect to other granule cell dendrites. This is an example of ''synaptic reorganization''. This was noted in human tissue in 1974 and in animal models in 1985. In TLE, the sprouting mossy fibres are larger than in the normal brain and their connections may be aberrant. Mossy fibre sprouting continues from one week to two months after injury. Aberrant mossy fibre sprouting may create excitatory feedback circuits that lead to temporal lobe seizures. This is evident in intracellular recordings. Stimulation of aberrant mossy fibre areas increases the
excitatory postsynaptic potential In neuroscience, an excitatory postsynaptic potential (EPSP) is a postsynaptic potential that makes the postsynaptic neuron more likely to fire an action potential. This temporary depolarization of postsynaptic membrane potential, caused by the ...
response. However, aberrant mossy fiber sprouting may inhibit excitatory transmission by synapsing with basket cells which are inhibitory neurons and by releasing GABA and
neuropeptide Y Neuropeptide Y (NPY) is a 36 amino-acid neuropeptide that is involved in various physiological and homeostatic processes in both the central and peripheral nervous systems. NPY has been identified as the most abundant peptide present in the ma ...
which are
inhibitory neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neur ...
s. Also, in animal models, granule cell hyper-excitability is recorded before aberrant mossy fibre sprouting has occurred.


Diagnosis

Epileptic spike and wave discharges monitored with EEG The diagnosis of temporal lobe epilepsy can include the following methods:
Magnetic resonance imaging Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio wave ...
(MRI), CT scans,
positron emission tomography Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in Metabolism, metabolic processes, and in other physiological activities including bl ...
(PET),
EEG Electroencephalography (EEG) is a method to record an electrogram of the spontaneous electrical activity of the brain. The biosignals detected by EEG have been shown to represent the postsynaptic potentials of pyramidal neurons in the neocortex ...
, and
magnetoencephalography Magnetoencephalography (MEG) is a functional neuroimaging technique for mapping brain activity by recording magnetic fields produced by electrical currents occurring naturally in the brain, using very sensitive magnetometers. Arrays of SQUIDs (s ...
.


Imaging

CT scan is useful as the emergency situations when the suspected cause of epilepsy is due to conditions such as
intracerebral haemorrhage Intracerebral hemorrhage (ICH), also known as cerebral bleed, intraparenchymal bleed, and hemorrhagic stroke, or haemorrhagic stroke, is a sudden bleeding into the tissues of the brain, into its ventricles, or into both. It is one kind of bleed ...
, or
brain abscess Brain abscess (or cerebral abscess) is an abscess caused by inflammation and collection of infected material, coming from local (ear infection, dental abscess, infection of paranasal sinuses, infection of the mastoid air cells of the temporal bone ...
es, or when MRI imaging is not readily available or there is any contraindications to MRI such as the presence of
cardiac pacemaker 350px, Image showing the cardiac pacemaker or SA node, the primary pacemaker within the electrical_conduction_system_of_the_heart">SA_node,_the_primary_pacemaker_within_the_electrical_conduction_system_of_the_heart. The_muscle_contraction.htm ...
s or
cochlear implant A cochlear implant (CI) is a surgically implanted neuroprosthesis that provides a person who has moderate-to-profound sensorineural hearing loss with sound perception. With the help of therapy, cochlear implants may allow for improved speech und ...
s in the subject's body. CT scan also detect some abnormal calcifications in the brain that is characteristic of diseases such as
tuberous sclerosis Tuberous sclerosis complex (TSC) is a rare multisystem autosomal dominant genetic disease that causes non-cancerous tumours to grow in the brain and on other vital organs such as the kidneys, heart, liver, eyes, lungs and skin. A combination ...
and
Sturge–Weber syndrome Sturge–Weber syndrome, sometimes referred to as encephalotrigeminal angiomatosis, is a rare congenital neurological and skin disorder. It is one of the phakomatoses and is often associated with port-wine stains of the face, glaucoma, seizures, i ...
. However, CT scan is not sensitive or specific enough when compared in MRI in detecting the common causes of epilepsy such as small tumours, vascular malformations, abnormalities of
cerebral cortex The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consisting of ...
development, or abnormalities in the medial part of the temporal lobe. MRI is the imaging choice when assessing those with epilepsy. In newly diagnosed epilepsy, MRI can detect brain lesion in up to 12 to 14% of the cases. However, for those with chronic epilepsy, MRI can detect brain lesion in 80% of the cases. However, in cases where there is definite clinical and EEG diagnosis of
idiopathic generalized epilepsy Idiopathic generalized epilepsy (IGE) is a group of epileptic disorders that are believed to have a strong underlying genetic basis. Patients with an IGE subtype are typically otherwise normal and have no structural brain abnormalities. People als ...
, or Rolandic epilepsy, MRI scan is not needed.


Differential diagnosis

Other medical conditions with similar symptoms include
panic attacks Panic attacks are sudden periods of intense fear and discomfort that may include palpitations, sweating, chest pain or chest discomfort, shortness of breath, trembling, dizziness, numbness, confusion, or a feeling of impending doom or of losing ...
, psychosis spectrum disorders,
tardive dyskinesia Tardive dyskinesia (TD) is a disorder that results in involuntary repetitive body movements, which may include grimacing, sticking out the tongue or smacking the lips. Additionally, there may be rapid jerking movements or slow writhing movemen ...
, and
occipital lobe The occipital lobe is one of the four major lobes of the cerebral cortex in the brain of mammals. The name derives from its position at the back of the head, from the Latin ''ob'', "behind", and ''caput'', "head". The occipital lobe is the vi ...
epilepsy.


Treatments


Anticonvulsants

Many
anticonvulsant Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of b ...
oral medications are available for the management of temporal lobe seizures. Most anticonvulsants function by decreasing the excitation of
neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
s, for example, by blocking fast or slow
sodium channel Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels and can be classified according to the trigger that opens the channel ...
s or by modulating
calcium channels A calcium channel is an ion channel which shows selective permeability to calcium ions. It is sometimes synonymous with voltage-gated calcium channel, although there are also ligand-gated calcium channels. Comparison tables The following tables ex ...
; or by enhancing the inhibition of neurons, for example by potentiating the effects of inhibitory
neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neuro ...
s like GABA. In TLE, the most commonly used older
medications A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and rel ...
are
phenytoin Phenytoin (PHT), sold under the brand name Dilantin among others, is an anti-seizure medication. It is useful for the prevention of tonic-clonic seizures (also known as grand mal seizures) and focal seizures, but not absence seizures. The intr ...
,
carbamazepine Carbamazepine (CBZ), sold under the trade name Tegretol among others, is an anticonvulsant medication used primarily in the treatment of epilepsy and neuropathic pain. It is used as an adjunctive treatment in schizophrenia along with other m ...
,
primidone Primidone, sold under various brand names, is a barbiturate medication that is used to treat partial and generalized seizures, as well as essential tremors. It is taken by mouth. Common side effects include sleepiness, poor coordination, nau ...
,
valproate Valproate (VPA) and its valproic acid, sodium valproate, and valproate semisodium forms are medications primarily used to treat epilepsy and bipolar disorder and prevent migraine headaches. They are useful for the prevention of seizures in those ...
, and
phenobarbital Phenobarbital, also known as phenobarbitone or phenobarb, sold under the brand name Luminal among others, is a medication of the barbiturate type. It is recommended by the World Health Organization (WHO) for the treatment of certain types of ep ...
. Newer drugs, such as
gabapentin Gabapentin, sold under the brand name Neurontin among others, is an anticonvulsant medication primarily used to treat partial seizures and neuropathic pain. It is a first-line medication for the treatment of neuropathic pain caused by diabet ...
,
topiramate Topiramate, sold under the brand name Topamax among others, is a carbonic anhydrase inhibitor medication used to treat epilepsy and prevent migraines. It has also been used in alcohol dependence. For epilepsy this includes treatment for gener ...
,
levetiracetam Levetiracetam, sold under the brand name Keppra among others, is a medication used to treat epilepsy. It is used for partial-onset, myoclonic, or tonic–clonic seizures and is taken either by mouth as an immediate or extended release formul ...
,
lamotrigine Lamotrigine, sold under the brand name Lamictal among others, is a medication used to treat epilepsy and stabilize mood in bipolar disorder. For epilepsy, this includes focal seizures, tonic-clonic seizures, and seizures in Lennox-Gastaut synd ...
,
pregabalin Pregabalin, sold under the brand name Lyrica among others, is an anticonvulsant, analgesic and anxiolytic medication used to treat epilepsy, neuropathic pain, fibromyalgia, restless leg syndrome, opioid withdrawal and generalized anxiety disord ...
,
tiagabine Tiagabine (trade name Gabitril) is an anticonvulsant medication produced by Cephalon that is used in the treatment of epilepsy. The drug is also used off-label in the treatment of anxiety disorders and panic disorder. Medical uses Tiagabine is a ...
,
lacosamide Lacosamide, sold under the brand name Vimpat among others, is a medication used for the treatment of partial-onset seizures and primary generalized tonic-clonic seizures. It is used by mouth or intravenously. It is available as a generic medic ...
, and
zonisamide Zonisamide, sold under the brand name Zonegran among others, is a medication used to treat the symptoms of epilepsy and Parkinson's disease. Chemically it is a sulfonamide. It serves as an anticonvulsant used primarily as an adjunctive therapy ...
promise similar effectiveness, with possibly fewer
side-effects In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...
.
Felbamate Felbamate (marketed under the brand name Felbatol by MedPointe) is an anticonvulsant used in the treatment of epilepsy. It is used to treat partial seizures (with and without generalization) in adults and partial and generalized seizures associa ...
and
vigabatrin Vigabatrin, brand name Sabril, is a medication used to treat epilepsy. It became available as a generic medication in 2019. It works by inhibiting the breakdown of γ-aminobutyric acid (GABA). It is also known as γ-vinyl-GABA, and is a stru ...
are newer, but can have serious adverse effects so they are not considered as first-line treatments. Up to one third of patients with medial temporal lobe epilepsy will not have adequate seizure control with medication alone. For patients with medial TLE whose seizures remain uncontrolled after trials of several types of anticonvulsants (that is, the epilepsy is ''intractable''), surgical excision of the affected temporal lobe may be considered.


Surgical interventions

Epilepsy surgery has been performed since the 1860s and doctors have observed that it is highly effective in producing freedom from seizures. However, it was not until 2001 that a scientifically sound study was carried out to examine the effectiveness of temporal lobectomy. Temporal lobe surgery can be complicated by decreased
cognitive function Cognitive skills, also called cognitive functions, cognitive abilities or cognitive capacities, are brain-based skills which are needed in acquisition of knowledge, manipulation of information and reasoning. They have more to do with the mechanisms ...
. However, after temporal lobectomy, memory function is supported by the opposite temporal lobe; and recruitment of the frontal lobe. Cognitive rehabilitation may also help.


Other treatments

Where surgery is not recommended, further management options include new (including experimental)
anticonvulsant Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of b ...
s, and
vagus nerve stimulation Vagus nerve stimulation (VNS) is a medical treatment that involves delivering electrical impulses to the vagus nerve. It is used as an add-on treatment for certain types of intractable epilepsy and treatment-resistant depression. Medical use VNS ...
. The
ketogenic diet The ketogenic diet is a high- fat, adequate-protein, low-carbohydrate dietary therapy that in conventional medicine is used mainly to treat hard-to-control (refractory) epilepsy in children. The diet forces the body to burn fats rather than ca ...
is also recommended for children, and some adults. Other options include brain cortex responsive neural stimulators,
deep brain stimulation Deep brain stimulation (DBS) is a neurosurgical procedure involving the placement of a medical device called a neurostimulator, which sends electrical impulses, through implanted electrodes, to specific targets in the brain (the brain nucleu ...
,
stereotactic radiosurgery Stereotactic surgery is a minimally invasive form of surgical intervention that makes use of a three-dimensional coordinate system to locate small targets inside the body and to perform on them some action such as ablation, biopsy, lesion, injec ...
, such as the
gamma knife Radiosurgery is surgery using radiation, that is, the destruction of precisely selected areas of tissue using ionizing radiation rather than excision with a blade. Like other forms of radiation therapy (also called radiotherapy), it is usually u ...
, and
laser ablation Laser ablation or photoablation (also called laser blasting) is the process of removing material from a solid (or occasionally liquid) surface by irradiating it with a laser beam. At low laser flux, the material is heated by the absorbed laser ...
.


Effects on society

The first to record and catalog the abnormal symptoms and signs of TLE was
Norman Geschwind Norman Geschwind (January 8, 1926 – November 4, 1984) was a pioneering American Behavioral neurology, behavioral neurologist, best known for his exploration of behavioral neurology through disconnection models based on lesion analysis. Earl ...
. He found a constellation of symptoms that included
hypergraphia Hypergraphia is a behavioral condition characterized by the intense desire to write or draw. Forms of hypergraphia can vary in writing style and content. It is a symptom associated with temporal lobe changes in epilepsy and in Geschwind syndrome ...
,
hyperreligiosity Hyperreligiosity is a psychiatric disturbance in which a person experiences intense religious beliefs or episodes that interfere with normal functioning. Hyperreligiosity generally includes abnormal beliefs and a focus on religious content or eve ...
,
collapse Collapse or its variants may refer to: Concepts * Collapse (structural) * Collapse (topology), a mathematical concept * Collapsing manifold * Collapse, the action of collapsing or telescoping objects * Collapsing user interface elements ** ...
, and pedantism, now called ''
Geschwind syndrome Geschwind syndrome, also known as Gastaut-Geschwind, is a group of behavioral phenomena evident in some people with temporal lobe epilepsy. It is named for one of the first individuals to categorize the symptoms, Norman Geschwind, who published prol ...
''.
Vilayanur S. Ramachandran Vilayanur Subramanian Ramachandran (born 10 August 1951) is an Indian-American neuroscientist. He is known for his wide-ranging experiments and theories in behavioral neurology, including the invention of the mirror box. Ramachandran is a disti ...
explored the neural basis of the hyperreligiosity seen in TLE using the
galvanic skin response Electrodermal activity (EDA) is the property of the human body that causes continuous variation in the electrical characteristics of the skin. Historically, EDA has also been known as skin conductance, galvanic skin response (GSR), electrodermal ...
(GSR), which correlates with emotional arousal, to determine whether the hyperreligiosity seen in TLE was due to an overall heightened emotional state or was specific to religious stimuli. Ramachandran presented two subjects with neutral, sexually arousing and religious words while measuring GSR. Ramachandran was able to show that patients with TLE showed enhanced emotional responses to the religious words, diminished responses to the sexually charged words, and normal responses to the neutral words. This study was presented as an abstract at a neuroscience conference and referenced in Ramachandran's book, ''
Phantoms in the Brain ''Phantoms in the Brain: Probing the Mysteries of the Human Mind'' (also published as ''Phantoms in the Brain: Human Nature and the Architecture of the Mind'') is a 1998 popular science book by neuroscientist V.S. Ramachandran and ''New York Time ...
'', but it has never been published in the
peer-review Peer review is the evaluation of work by one or more people with similar competencies as the producers of the work (peers). It functions as a form of self-regulation by qualified members of a profession within the relevant field. Peer review ...
ed scientific press. A study in 2015, reported that intrinsic religiosity and religiosity outside of organized religion were higher in patients with epilepsy than in the
control group In the design of experiments, hypotheses are applied to experimental units in a treatment group. In comparative experiments, members of a control group receive a standard treatment, a placebo, or no treatment at all. There may be more than one tr ...
. Lower education level, abnormal background EEG activity, and hippocampal sclerosis have been found to be contributing factors for religiosity in TLE. TLE has been suggested as a materialistic explanation for the revelatory experiences of prominent religious figures such as
Abraham Abraham, ; ar, , , name=, group= (originally Abram) is the common Hebrew patriarch of the Abrahamic religions, including Judaism, Christianity, and Islam. In Judaism, he is the founding father of the special relationship between the Jew ...
,
Moses Moses hbo, מֹשֶׁה, Mōše; also known as Moshe or Moshe Rabbeinu (Mishnaic Hebrew: מֹשֶׁה רַבֵּינוּ, ); syr, ܡܘܫܐ, Mūše; ar, موسى, Mūsā; grc, Mωϋσῆς, Mōÿsēs () is considered the most important pro ...
,
Jesus Jesus, likely from he, יֵשׁוּעַ, translit=Yēšūaʿ, label=Hebrew/Aramaic ( AD 30 or 33), also referred to as Jesus Christ or Jesus of Nazareth (among other names and titles), was a first-century Jewish preacher and religious ...
,
Mohammed Muhammad ( ar, مُحَمَّد;  570 – 8 June 632 CE) was an Arab religious, social, and political leader and the founder of Islam. According to Islamic doctrine, he was a prophet divinely inspired to preach and confirm the monoth ...
,
Saint Paul Paul; grc, Παῦλος, translit=Paulos; cop, ⲡⲁⲩⲗⲟⲥ; hbo, פאולוס השליח (previously called Saul of Tarsus;; ar, بولس الطرسوسي; grc, Σαῦλος Ταρσεύς, Saũlos Tarseús; tr, Tarsuslu Pavlus; ...
,
Joan of Arc Joan of Arc (french: link=yes, Jeanne d'Arc, translit= an daʁk} ; 1412 – 30 May 1431) is a patron saint of France, honored as a defender of the French nation for her role in the siege of Orléans and her insistence on the coronati ...
,
Saint Teresa of Ávila In religious belief, a saint is a person who is recognized as having an exceptional degree of holiness, likeness, or closeness to God. However, the use of the term ''saint'' depends on the context and denomination. In Catholic, Eastern Orth ...
, and
Joseph Smith Joseph Smith Jr. (December 23, 1805June 27, 1844) was an American religious leader and founder of Mormonism and the Latter Day Saint movement. When he was 24, Smith published the Book of Mormon. By the time of his death, 14 years later, he ...
. These experiences are described (in possibly unreliable accounts) as complex interactions with their visions; but possibly (and dependent on the reliability of historical accounts, often made by acolytes) lack the stereotypy, amnestic periods, and automatisms or generalized motor events, which are characteristic of TLE. Psychiatric conditions with
psychotic spectrum A spectrum disorder is a mental disorder that includes a range of linked conditions, sometimes also extending to include singular symptoms and traits. The different elements of a spectrum either have a similar appearance or are thought to be cause ...
symptoms might be more plausible physical explanation of these experiences. It has been suggested that
Pope Pius IX Pope Pius IX ( it, Pio IX, ''Pio Nono''; born Giovanni Maria Mastai Ferretti; 13 May 1792 – 7 February 1878) was head of the Catholic Church from 1846 to 1878, the longest verified papal reign. He was notable for convoking the First Vatican ...
's doctrine of the
immaculate conception The Immaculate Conception is the belief that the Virgin Mary was free of original sin from the moment of her conception. It is one of the four Marian dogmas of the Catholic Church, meaning that it is held to be a divinely revealed truth w ...
was influenced by his forensically diagnosed partial epilepsy. In 2016, a case history found that a male temporal lobe epileptic patient experienced a vision of God following a temporal lobe seizure, while undergoing EEG monitoring. The patient reported that God had sent him to the world to "bring redemption to the people of
Israel Israel (; he, יִשְׂרָאֵל, ; ar, إِسْرَائِيل, ), officially the State of Israel ( he, מְדִינַת יִשְׂרָאֵל, label=none, translit=Medīnat Yīsrāʾēl; ), is a country in Western Asia. It is situated ...
". The purported link between TLE and religiosity has inspired work by
Michael Persinger Michael A. Persinger (June 26, 1945 – August 14, 2018) was an American-Canadian professor of psychology at Laurentian University, a position he had held from 1971 until his death in 2018. His most well-known hypotheses include the temporal lob ...
and other researchers in the field of
neurotheology The neuroscience of religion, also known as neurotheology and as spiritual neuroscience, attempts to explain religious experience and behaviour in neuroscientific terms. It is the study of correlations of neural phenomena with subjective experien ...
. Others have questioned the evidence for a link between temporal lobe epilepsy and religiosity.Benson, D.F. & Hermann, B.P. (1998) Personality disorders. In J. Engel Jr. & T.A. Pedley (Eds.) ''Epilepsy: A comprehensive textbook. Vol. II'' (pp. 2065–2070). Philadelphia: Lippincott–Raven.


References

{{DEFAULTSORT:Temporal Lobe Epilepsy Epilepsy types Neurotheology Temporal lobe