Temporal lobe epilepsy

Temporal lobe epilepsy' a.k.a. Psychomotor epilepsy, is a form of focal epilepsy, a chronic neurological condition characterized by recurrent seizures. Over 40 types of epilepsies are known. 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.

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.
 * 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 may begin when there is a very early insult to the left or right hippocampus that causes neuron death. 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 more drastically than in adults. In some children, elevated body temperature can cause febrile seizures. Febrile seizures are relatively normal as they occur in 2-5% of children under age 5 years. They typically last only a few minutes or even a matter of seconds, but are neither severe motor convulsions nor followed by weakness on one side of the body. In a small number of babies, these convulsions can last for over an hour and involve repeated convulsive episodes. These are known as complex febrile seizures and may be causatively 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. 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. 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. 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. Some studies suggest that HHV-6 infection happens prior to the occurrence of febrile seizures. However, only a minority of primary HHV-6 infections may be associated with febrile seizures. Secondly, other studies found HHV-6 DNA in brain tissue removed during surgery for MTLE.

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 occasionally seen in temporal lobe epilepsy and has been linked to the downregulation of reelin, a protein that normally keeps the layer compact by containing the neuronal migration. It is unknown whether changes in reelin expression play a role in epilepsy.

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.
 * 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 his or her environment. 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.
 * 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 (tonic) in either a flexed or extended position and then clonic jerking of the limbs often occurs. GTCS are often known in the vernacular as convulsions or "grand mal" (cf. French, grand maladie) seizures.

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.

Local and national laws exist regarding the operation of vehicles, aircraft and vessels by patients with epilepsy. Most licensing departments do not allow driving of vehicles by persons with CPS or GTCS until they have been seizure-free for a specified period of time. The laws are complex and varied; affected persons must check with the appropriate licensing authority. In a few locations, health care providers are legally-required to report patients with epilepsy (and other medical conditions which cause episodes of altered consciousness) to their local department of motor vehicles.

Treatments
There are many oral medications available for the management of epileptic seizures. They were previously called anticonvulsants however this term is misleading because most seizures are not convulsions. The modern term is antiepileptic drugs (AEDs). 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 medial temporal lobe epilepsy (up to one-third) will not experience adequate seizure control with medication.

For patients with medial TLE whose seizures remain uncontrolled after trials of several AEDs (intractable), resective surgery should be considered. 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. 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 a person must 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. For children, the ketogenic diet may also be tried. 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.

Temporal Lobe Epilepsy and the Arts
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 Vincent Van Gogh, Charles Dodgson (a.k.a. Lewis Carroll), Edgar Allan Poe, Fyodor Dostoevsky (whose novel The Idiot features a protagonist with epilepsy, Prince Myshkin), Gustave Flaubert, Philip K. Dick, Sylvia Plath and contemporary author Thom Jones. Peter O'Leary has also discussed this in relation to work of poet Philip Jenks 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 heightened emotional state or 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.

Cognitive neuroscience researcher Michael Persinger asserts that stimulating the temporal lobe electromagnetically can cause TLE and trigger hallucinations of apparent paranormal phenomena such as ghosts and UFOs. Persinger has even created a "God helmet" which purportedly can evoke altered states of consciousness through stimulation of the parietal and temporal lobes. Neurotheologians speculate that individuals with temporal lobe epilepsy, having a natural tendency to experience states of consciousness such as euphoria or samādhi, have functioned in human history as religious figures or shamans.

Temporal lobe epilepsy and hormones
Sex hormones can influence the timing and frequency of seizure activity. Estrogen is pro-epileptic and progesterone is anti-epileptic. These counterbalancing effects may account for "catamenial epilepsy" i.e. epilepsy preceding or made more severe prior to menstruation or during peri-ovulation. Gender may differentially influence neocortical pathologies in patients with refractory temporal lobe epilepsy.

Media Depictions

 * Film The Exorcism of Emily Rose, 2005.
 * Film Deceiver, 1997.
 * Film Happy Accidents, 2001.
 * Law and Order: Criminal Intent episode "The Gift," 2003.
 * 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 "Day Break" 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