Temporal lobe epilepsy

Temporal lobe epilepsy is a form of focal epilepsy, a chronic neurological condition characterized by recurrent seizures. Over 40 types of epilepsies are known.^[1] They fall into two main categories: partial-onset (focal or localization-related) epilepsies and generalized-onset epilepsies. Partial-onset epilepsies account for about 60% of all adult epilepsy cases, and temporal lobe epilepsy (TLE) is the most common single form causing refractory epilepsy.^[2]

Temporal lobe epilepsies are a group of medical disorders in which humans and animals experience recurrent epileptic seizures arising from one or both temporal lobes of the brain. Two main types are internationally recognized according to the International League Against Epilepsy.^[1]

• Mesial temporal lobe epilepsy (MTLE) arises in the hippocampus, parahippocampal gyrus and amygdala which are located in the inner aspect of the temporal lobe.
• Lateral temporal lobe epilepsy (LTLE) arises in the neocortex on the outer surface of the temporal lobe of the brain.

Because of strong interconnections, seizures beginning in either the medial or lateral temporal areas often spread to involve both areas and also to neighboring areas on the same side of the brain as well as the temporal lobe on the opposite side of the brain. The causes or etiology of different temporal lobe epilepsies vary and are discussed below.

Syndrome of Temporal Lobe Epilepsy (TLE)

The classical syndrome of TLE begins when there is a very early insult to the left or right hippocampus. Infants may develop lung or skin infections resulting in a fever. Babies have an immature thermoregulation system, and the fever causes the baby's core body temperature to increase. The raised body temperature can cause febrile seizures (convulsions). Febrile seizures occur in 2-5% of children under age 5 years. They are usually simple, lasting only a few minutes and not accompanied by postictal weakness on one side of the body or repeated seizures. In a small number of babies the febrile convulsions can last for an hour, be repeated, or be associated with postictal weakness on one side. These are known as complex febrile seizures, and may be later associated with TLE. As discussed below in the section on causes, it remains controversial whether complex febrile seizures actually cause TLE, or whether they are simply the earliest manifestation of the TLE condition.

Causes

A link between febrile seizures (seizures coinciding with episodes of fever in young children) and subsequent temporal lobe epilepsy has been suggested, but the exact role remains unclear.^{[3][4][5][6][7]} Some studies have shown abnormalities of the hippocampus on magnetic resonance imaging (MRI) in status epilepticus, which supports the theory that prolonged seizures damage the brain.^[8][9][10] Interestingly, some cases of MTLE present without the typical changes of mesial temporal sclerosis or other abnormalities on MRI scans. This has been termed paradoxical mesial temporal lobe epilepsy. The epilepsy in these patients tends to occur at a later age, which might suggest that an early event leads to hippocampal damage causing MTLE.^[11][12] Although this theory needs confirmation, some studies have pointed to human herpesvirus 6 (HHV-6) as a possible link between febrile convulsions and later MTLE. Firstly, several studies suggest that HHV-6 infection occurs commonly prior to the occurrence of febrile seizures.^{[13][14][15][16]} However, only a minority of primary HHV-6 infections may be associated with febrile seizures.^[17] Secondly, other studies found HHV-6 DNA in brain tissue removed during surgery for MTLE.^{[18][19][20][21]}

Rarely, MTLE can be hereditary or related to brain tumors, spinal meningitis, encephalitis, head injury or blood vessel malformations. MTLE can occur in association with other brain malformations. Most often, a cause cannot be determined with certainty.

LTLE is less common. It can be hereditary, as in Autosomal Dominant Lateral Temporal Lobe Epilepsy (ADLTLE) with auditory or visual features, but can also be associated with tumors, meningitis, encephalitis, trauma, vascular malformations or congenital brain malformations. Again, in many affected persons it is common that no cause can be identified.

Dispersion of granule cell layer in the hippocampal dentate gyrus is a major feature of temporal lobe epilepsy and is linked to the downregulation of reelin,^[22][23] a protein that normally keeps the layer compact by containing the neuronal migration.

Symptoms

The symptoms felt by the person, and the signs observable by others, during seizures which begin in the temporal lobe depend upon the specific regions of the temporal lobe and neighboring brain areas affected by the seizure. The International Classification of Epileptic Seizures published in 1981 by the International League Against Epilepsy (ILAE) recognizes three types of seizures which persons with TLE may experience.^[24]

1. Simple Partial Seizures (SPS) involve small areas of the temporal lobe such as the amygdala or the hippocampus. The term "simple" means that consciousness is not altered. In temporal lobe epilepsy SPS usually only cause sensations. These sensations may be mnestic such as déjà vu (a feeling of familiarity), jamais vu (a feeling of unfamiliarity), a specific single or set of memories, or amnesia. The sensations may be auditory such as a sound or tune, gustatory such as a taste, or olfactory such as a smell that is not physically present. Sensations can also be visual, involve feelings on the skin or in the internal organs. The latter feelings may seem to move over the body. Psychic sensations can occur such as an out-of-body feeling. Dysphoric or euphoric feelings, fear, anger, and other sensations can also occur during SPS. Often, it is hard for persons with SPS of TLE to describe the feeling. SPS are often called "auras" by lay persons who mistake them for a warning sign of a subsequent seizure. In fact, they are indeed seizures. Persons experiencing only SPS may not recognize what they are or seek medical advice about them. SPS may or may not progress to the seizure types listed below.
2. Complex Partial Seizures (CPS) by definition are seizures which impair consciousness to some extent. This is to say that they alter the person's ability to interact with others. They usually begin with an SPS, but then the seizure spreads to a larger portion of the temporal lobe resulting in impaired consciousness. Signs may include motionless staring, automatic movements of the hands or mouth, altered ability to respond to others, unusual speech, or unusual behaviors. Because judgement is impaired, persons experiencing CPS may not legally drive vehicles for periods of time which are set by local governments worldwide.
3. Seizures which begin in the temporal lobe but then spread to the whole brain are known as Secondarily Generalized Tonic-Clonic Seizures (SGTCS). These begin with an SPS or CPS phase initially, but then the arms, trunk and legs stiffen in either a flexed or extended position. After this, coarse jerking of the limbs and trunk occur.

Following each of these seizures, there is some period of recovery in which neurological function is altered. This is called the postictal state. The degree and length of the impairment directly correlates with the severity of the 3 seizure types listed above. SPS often last less than 60 seconds, CPS often last less than 2 minutes, and SGTCS usually last less than 3 minutes. The postictal state in the case of CPS and GTCS often lasts much longer than the seizure ictus itself. Because a major function of the temporal lobe is short-term memory, CPS and GTCS cause amnesia for the seizure. As a result, many persons with temporal lobe CPS and GTCS will not remember having had a seizure.

Treatments

There are many oral medications available for the management of epileptic seizures. They were previously called anticonvulsants but this term is misleading owing to the fact that most seizures are not convulsions. The modern term is antiepileptic drugs or AEDs, for short. In TLE, the most commonly used older AEDs are phenytoin, carbamazepine, primidone, valproate and phenobarbital. Newer drugs, such as gabapentin, topiramate, levetiracetam, lamotrigine, pregabalin, tiagabine, lacosamide, and zonisamide promise similar effectiveness, possibly with fewer side-effects. Felbamate and vigabatrin are newer AEDs, but can have serious adverse effects so they are not considered first-line AEDs. Nearly all AEDs function by decreasing the excitation of neurons (e.g., by blocking fast or slow sodium channels or modulating calcium channels) or by enhancing the inhibition of neurons (e.g., by potentiating the effects of inhibitory neurotransmitters like GABA). Unfortunately, many patients with mesial temporal lobe epilepsy (up to one-third) will not experience adequate seizure control with medication.^[25]

For patients with mesial TLE whose seizures remain uncontrolled after trials of several AEDs (intractable), resective surgery should be considered.^[26] Epilepsy surgery has been performed since the 1860s and physicians and surgeons had observed for decades that it was highly effective in producing seizure freedom. However, it was not until 2001 that a scientifically sound study was performed on the effectiveness of temporal lobectomy.^[27] This study proved that after the failure of several AEDs to control seizures in TLE temporal lobe surgery is far more effective in producing seizure freedom than is additional medication trials. The unanswered question that remains is how many medications must a person fail before considering surgery. A United States sponsored research study called ERSET was begun to answer the question of whether surgery can successfully be performed early in the course of TLE. Although the study ended earlier than anticipated, limited results are expected soon.

In preparation for these surgeries, patients are monitored by various methods to determine the focus of their seizures (that is, the region of the brain where seizures tend to arise before spreading). This can be done with video-EEG monitoring, intracranial EEG (where electrodes are placed beneath the skull, either within or resting just outside the brain), or SPECT imaging. MRI studies may additionally be used to seek evidence of hippocampal sclerosis. Once the epileptic focus has been determined, it can be excised, which usually involves removing part of the hippocampus and often the amygdala. To avoid removing areas of the brain responsible for speech (so-called "eloquent" areas), the surgical team will conduct a Wada test pre-operatively, wherein amobarbital is injected in the left or right carotid artery to temporarily quiet one half of the brain. If the patient performs poorly on neuropsychological testing during the intracarotid amobarbital (Wada) test, the surgical team may advise the patient against surgery or may offer a more limited operation.

If a person is not an optimal candidate for epilepsy surgery, then AEDs not previously tried, the vagus nerve stimulator, or AEDs in clinical research trials might be alternative treatments. Other possible future therapies such as brain cortex responsive neural stimulators, deep brain stimulation), and stereotactic radiosurgery (such as gamma knife) are undergoing research studies for treatment of TLE and other forms of epilepsy.

Social and artistic influence

Temporal Lobe Epilepsy and the Arts

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As Eve LaPlante discusses in her book, Seized, the intense emotions, sensory experience including vibrancy of colors, and particular mental state provoked by temporal lobe abnormalities may have contributed to the creation of significant works of art. A number of well-known writers and artists are known, or in many cases suspected to have had temporal lobe epilepsy, aggravated, in some cases, by alcoholism. They include Charles Dodgson (a.k.a. Lewis Carroll), Edgar Allan Poe, Fyodor Dostoevsky (whose novel The Idiot features an epileptic protagonist, Prince Myshkin), Gustave Flaubert, Philip K. Dick, Sylvia Plath and contemporary author Thom Jones. Peter O'Leary has also discussed this in his "Gnostic Contagion: Robert Duncan and the Poetry of Illness". Sadi Ranson-Polizzotti has discussed the significance of Lewis Carroll's epilepsy online and in a forthcoming book on the subject.

Temporal Lobe Epilepsy, Neurotheology and Paranormal Experience

The first researcher to note and catalog the abnormal experiences associated with TLE was neurologist Norman Geschwind, who noted a constellation of symptoms, including hypergraphia, hyperreligiosity, fainting spells, and pedantism, often collectively ascribed to a condition known as Geschwind syndrome.

Vilayanur S. Ramachandran explored the neural basis of the hyperreligiosity seen in TLE using galvanic skin response, which correlates with emotional arousal, to determine whether the hyperreligiosity seen in TLE was due to an overall enhanced emotional response, or if the enhancement was specific to religious stimuli (Ramachandran and Blakeslee, 1998). By presenting 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. These results suggest that the medial temporal lobe is specifically involved in generating some of the emotional reactions associated with religious words, images and symbols.

UFO Researcher Albert Budden and cognitive neuroscience researcher Michael Persinger assert that increases in local electromagnetism, triggering the temporal lobe can stimulate TLE and trigger hallucinations of apparent paranormal phenomena, for example ghosts and UFOs. Persinger has even gone as far as to create a "God helmet" to apparently demonstrate how stimulation of the parietal and temporal lobe can evoke altered states of consciousness. Quite possibly, as neurotheologians have speculated, then, individuals with temporal lobe epilepsy, who have a natural aptitude for "religious" states of consciousness (such as euphoria or samādhi) have functioned in human history as religious figures or as shamans. Persinger's theories, however, remain controversial.^{[by whom?]}

Temporal lobe epilepsy and hormones

Sex hormones can influence the timing and frequency of seizure activity. Estrogen is pro-epileptic and progestrone is anti-epileptic. These counterbalancing effects may account for the catamenial (pre-menstrual or peri-ovulation) worsening of seizures during the menstrual cycle in women. Gender may differentially influence neocortical pathologies in patients with refractory temporal lobe epilepsy.^[28]

See also

• God helmet
• Euphoria
• Amygdala
• Auras
• Bipolar Disorder
• Déjà vu
• Geschwind syndrome
• Hippocampal sclerosis
• Intermittent explosive disorder
• List of people with epilepsy
• Mediums
• Neurotheology
• Post-traumatic epilepsy
• Prosopagnosia (face blindness)
• Temporal lobe
• Religious ecstasy

Media Depictions

• Film The Exorcism of Emily Rose, 2005, (directed by Scott Derrickson. The screenplay was written by Scott Derrickson and Paul Harris Boardman.)
• Film Deceiver, 1997 (directed by Jonas and Josh Pate, starring Tim Roth, Michael Rooker, Chris Penn and Renée Zellweger)
• Film Happy Accidents, 2001 (directed by Brad Anderson, starring Marisa Tomei and Vincent D'Onofrio)
• Law and Order: Criminal Intent episode "The Gift," 2003, guest-starring Jane Adams
• Television show "Veronica Mars," 2004-2007, main character Veronica Mars suspected her ex-boyfriend Duncan Kane of murdering his sister and her best friend, Lilly Kane, after discovering he had been treated for TLE symptoms. (Wrongly described on the show as "Type Four Epilepsy.")
• Television show "Medium," 2005-, starring Patricia Arquette
• Television show "Firefly," 2002, film Serenity, 2005, both created by Joss Whedon, feature character River Tam, affected with symptoms of TLE after alteration of amygdala, brain component related to TLE
• A current story line on the CBS daytime drama, The Young and the Restless, features character Victor Newman being diagnosed with TLE.
• Television Show "ER," 2007, episode "Crisis of Consciousness", patient predicts engine will fall on his head if he is not moved.
• Television Show "Daybreak" on ABC, Jared is said to have TLE.
• Television show "Eli Stone," 2008, title character (Johnny Lee Miller) loosens life and changes priorities after neurological condition prompts auditory/extrasensory hallucinations, premonitions and dawning spiritual enlightenment.
• Book, "The Terminal Man" by Michael Crichton
• Book, "The Spiral Staircase" by Karen Armstrong, an autobiography including descriptions of her long undiagnosed Temporal lobe epilepsy.
• The music video for "Epilepsy is Dancing" from the album The Crying Light by Antony and the Johnsons

Further reading

• Book "Seized: Temporal Lobe Epilepsy as Medical, Historical and Artistic Phenomenon," by Eve LaPlante, 1993, reprinted 2000, discusses link between TLE and artistic creativity
• Transcript of Horizon documentary "God on the Brain" - http://www.bbc.co.uk/science/horizon/2003/godonbraintrans.shtml
• See "Theological Aspects of Temporal Lobe Function," by paraclete, http://www.everything2.com/index.pl?node_id=1747573, including bibliography:
• Bard P, 1934, "On emotional expression after decortication with some remarks on certain theoretical views", Psych. Reviews; 41:309-329
• Blumer D, 2002, "The illness of Vincent van Gogh", Am J Psychiatry; 159:519-526
• Broca P, 1878, "Anatomie comparé de circonvolutions cérébrales. Le grand lobe limbique et la scissure limbige dans la série des mammiféres", Revue d'Anthropologie; 1:385-498
• Cannon WB, 1927, "The James-Lange theory of emotion", Am J. Psychology; 39:106-124
• Dewhurt K, Beard AW, 1970, "Sudden religious conversions in temporal lobe epilepsy", Br. J. Psychiatry; 117:497-507
• Hohmann GW, 1966, "Some effects of spinal cord lesions on experienced emotional feelings", Psychophysiology; 3(2):143-56
• James W, 1884, "What is an emotion?", Mind; 9:188-205
• Kingsley RE, 2000, "Concise Text of Neuroscience", 2nd edition, Lippincott Williams and Wilkins, 884-888
• Lange CG, 1887, "Uber Gemuthsbewegungen", Liepzig: T Thomas
• Lowe J, Carroll D, 1985, "The effects of spinal injury on the intensity of emotional experience", Br J Clin Psychol.; 24(2):135-6
• MacLean PD, 1955, "The limbic system ("visceral brain") and emotional behaviour", Arch. Neurology and Psychiatry; 73:130-134
• Ogata A, Miyakawa T, 1998, "Religious experiences in epileptic patients with a focus on ictus-related episodes", Psychiatry and Clinical Neuroscience; 52:321-325
• Papez JW, 1937, "A proposed mechanism of emotion", Arch. Neurology and Psychiatry; 38:725-743
• Persinger MA, 1983, "Religious and mystical experiences as artefacts of temporal lobe function: a general hypothesis", Percept Mot Skills; 57(3):1255-62
• Ramachandran VS and Blakeslee, 1998, "Phantoms in the Brain", 1st edition, Fourth Estate, Chapter 9
• Thompson JG, 1988, "The Psychobiology of Emotion", 1st edition, New York: Plenum Press
• Lewis Carroll & Temporal Lobe Epilepsy articles, by Sadi Ranson-Polizzotti on What About Lewis Carroll

References