Mesial Temporal Lobe Epilepsy

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Continuing Education Activity

Mesial temporal lobe epilepsy (MTLE) is the most common form of focal epilepsy. This activity outlines the etiopathology, clinical presentation, diagnostic approach, and management of MTLE by an interprofessional team.


  • Outline the etiology and histopathological findings of mesial temporal lobe epilepsy.
  • Describe the seizure semiology in patients with mesial temporal lobe epilepsy.
  • Describe the characteristic EEG findings in patients with mesial temporal lobe epilepsy.
  • Review the treatment options available for patients with mesial temporal lobe epilepsy.


The temporal lobes are the most common brain region to develop epileptogenicity.[1] Historically, "uncinate fits" were first described by Hughlings Jackson in the 19th Century linking seizures presenting as "dreamy states" to lesions in the uncus of the temporal lobe. In the mid-20th century, the term "psychomotor epilepsy" was introduced by Gibbs and Gibbs to describe the characteristic psychic and emotional semiological findings of patients with seizures arising from the temporal lobes and their associated electrophysiologic features.[2] These experiential phenomena were later studied by Jasper and Penfield using intraoperative stimulation experiments and confirmed to arise from the temporal lobes.[3]

Mesial temporal lobe epilepsy (MTLE) is often discussed as a separate entity because it is quite distinct from its lateral counterpart in terms of etiology, semiology, imaging, and electrophysiologic characteristics. Moreover, the mesial temporal lobes tend to be the site of origin of close to 80% of all TLEs.[4]


Most cases of MTLE are sporadic in occurrence, although familial forms are not uncommon.[5] One study showed that as high as one-fifth of the newly diagnosed non-lesional MTLE could have a familial attribute. Research has identified a genetic locus for familial MTLE in a large family with autosomal dominant MTLE phenotype.[6] The familial MTLE cases have been shown to exhibit a complex inheritance pattern and usually do not exhibit mesial temporal sclerosis on imaging.[7]

Hippocampal sclerosis (HS) is the most common histopathological abnormality found in patients with drug-resistant TLE. In a European series of 9523 patients with epilepsy undergoing surgery, HS was identified in 36.4%,  long-term epilepsy-associated tumors (LEAT) in 23.6%, and focal cortical dysplasias (FCD) in 19.8%.[8] FCDs classify as malformations of cortical development (MCDs), which also include polymicrogyria, nodular heterotopia, and hamartomas, which are less common pathologies involved with temporal lobe epilepsy. Other less common etiologies include post-infectious (most commonly after HSV encephalitis), vascular malformations, ischemic lesions, inflammatory lesions, and old traumatic encephalomalacia.[9][10]


There does not seem to be a specific age or sexual predominance to MTLE. Patients usually have normal perinatal history and have normal development. They generally have a normal neurological examination and are cognitively intact. A childhood history of febrile seizures is an important harbinger for the development of MTLE.[11][12] A prospective study performed on 226 children with febrile status epilepticus [FEBSTAT] found evidence of acute hippocampal injury in 9.7% of patients. Subsequently, follow-up MRI of the brain on 14 of these 22 patients showed hippocampal sclerosis in 10 and hippocampal volume loss in 12.[13] Other less important risk factors include head trauma, birth trauma, childhood central nervous system (CNS) infection, and posterior cerebral artery territory infarcts.


Hippocampal sclerosis is histopathologically seen as segmental pyramidal cell loss in CA1, CA3, and CA4 regions, whereas CA2 pyramidal and dentate gyrus granule cells are most seizure resistant.[14] Neuronal cell loss is associated with reactive astrogliosis causing tissue stiffening, which has been traditionally termed as "Ammon's horn sclerosis."[15] Some of the proposed pathomechanisms include disruption of neuronal circuitries, causing aberrant mossy fiber sprouting and molecular rearrangement/plasticity of ion channel and neurotransmitter receptor expression.[16][17] Abnormalities have also been noted in the dentate gyrus in the form of granule cell dispersion.[18] Additionally, variable cell loss is also detectable in adjacent cortical regions, including the subiculum, entorhinal cortex, and amygdala.

Several classification systems have been proposed for HS. The most widely used is the ILAE classification system, which divides HS into three types based on a semi-quantitative survey of segmental cell loss within hippocampal subfields. International League Against Epilepsy (ILAE) type 1 has both CA1 and CA4 loss; ILAE Type 2 has predominant CA1 loss, and ILAE Type 3 has predominant CA4 loss.

Malformations of cortical development represent a wide range of cortical lesions resulting from the derangement of normal developmental processes involving cells implicated in the formation of the cortical mantle.[19] Focal cortical dysplasias (FCDs) represent the most common type of MCDs and characteristically demonstrate disruption of normal cortical lamination by the presence of 'large aberrant neurons' as well as 'grotesque cells' in both cortex and subcortical white matter.[20]

Gangliogliomas and dysembryoplastic neuroepithelial tumor (DNET) is the most frequent long-term epilepsy-associated tumors (LEAT) comprising 65% of brain tumors encountered in patients undergoing epilepsy surgery.[21][22]

History and Physical

Seizure Semiology

The International League Against Epilepsy (ILAE) has recently brought out an updated multilevel classification system for epilepsies to highlight the etiologic basis of the patient’s condition.[23] This update is a reflection of our gain understanding of the underlying mechanisms of epileptogenesis and is crucial in making rational treatment decisions. Based on this revision, patients with MTLE usually are classified as having focal epilepsy and manifest as focal onset seizures with or without impaired awareness.

When there is preserved awareness, the patient can describe the occurrence of unusual sensations known as auras. Auras could be visceral, autonomic, gustatory, or affective symptoms. Patients commonly experience a rising epigastric sensation, nausea, and olfactory and/or gustatory hallucination. Psychic sensations can occur, such as depersonalization (out-of-body feeling), déjà vu (a feeling of familiarity), jamais vu (feeling of unfamiliarity), déjà entendu (hearing familiar sounds), or panoramic visions (a rapid recollection of episodes from the past). Dysphoric or euphoric feelings, fear, terror, anger, and other sensations can also occur. Often, the patients find the aura hard to describe. Autonomic features include piloerection, pallor/flushing, tachycardia, or pupillary dilatation.[24] With the loss of awareness, patients have a behavioral arrest and portray a blank staring facial appearance, which is followed by the development of oro/facial/alimentary automatisms such as lip-smacking, chewing, sucking, or swallowing, which is usually accompanied by ipsilateral gestural automatisms such as repetitive hand movements, picking and/or fidgeting behavior, disrobing and contralateral dystonic posturing of limbs. The presence of speech suggests non-dominant hemispheric seizure onset, but its absence is not a reliable lateralizing finding. Patients commonly have a period of postictal confusion following the episode. Less commonly, episodes may progress to generalized tonic-clonic seizures.


Although the advent of antiepileptic medications has improved the quality of life of patients with epilepsy by reducing seizure frequency, many of the patients with MTLE have a greater tendency to become pharmacoresistant over time. Studies have shown that less than 25% of patients with MTLE remained seizure-free for greater than one year.[25] This data elucidates the importance of non-pharmacological therapies in patients having MTLE. However, most of these non-pharmacological modalities require accurate identification of the epileptogenic zone to provide successful seizure outcomes.

The basis of presurgical evaluation for epilepsy is to identify the epileptogenic zone, which is defined as the minimum amount of cortex that needs to be inactivated/resected/disconnected to render the patient seizure-free.[26] However, the epileptogenic zone is a theoretical construct, and its identification is a matter of careful approximation of all available information sources. These sources include electrophysiologic data obtained from electroencephalography (EEG) and magnetoencephalography (MEG) that have a good temporal resolution and various neuroimaging modalities such as magnetic resonance imaging (MRI,) interictal positron emission tomography (PET), ictal single-photon emission tomography (SPECT), subtracted ictal SPECT co-registered to MRI (SISCOM), and functional MRI that have a good spatial resolution. Neuropsychological assessment is also employed as a part of a presurgical evaluation to evaluate for functional characteristics of the affected epileptogenic region. Such an extensive evaluation can be performed most effectively at a comprehensive epilepsy center with a cohesive team of specialists with training in neurology, neurosurgery, neuroradiology, neuropsychology, neuropathology, and psychiatry liaison services.

High-resolution 3T/7T MRI of the brain with thin cuts obtained through the temporal lobes is a powerful tool to assess subtle structural abnormalities involving the mesial temporal structures. Additional information regarding hippocampal pathology is obtainable with the use of multiple MR modalities such as volumetry, spectroscopy, and Diffusion Tensor Imaging (DTI).[27] Interictal PET looks at hypometabolism and can identify the epileptogenic temporal lobe in up to 70% to 90% of patients with MTLE.[28] On the other hand, ictal SPECT/SISCOM looks at hyperperfusion and is also a useful tool, especially while looking at the origin and spread along the epileptogenic network.[29][30]

The goal of presurgical evaluation for epilepsy surgery is to lateralize and localize the seizure focus accurately; this includes phase I and phase II evaluation:

Phase I evaluation includes the use of non-invasive modalities to determine where the seizure starts; this includes techniques such as video-EEG, MEG, MRI, interictal PET, ictal SPECT/ SISCOM, and neuropsychological assessment. Patients with temporal lobe epilepsy involving the dominant temporal lobe also need functional MRI and/or intracarotid amobarbital/methohexital (Wada) test for language and memory lateralization.

Phase II evaluation includes the use of surgically placed electrodes directly over the brain parenchyma to determine where exactly the seizure is originating. This phase involves the use of invasive techniques such as placement of subdural grids/strips and/or depth electrode placement for electrocorticography (ECoG) and stereo-electroencephalography (SEEG).

Scalp Electroencephalogram 

The EEG background in patients with mesial temporal lobe epilepsy is usually normal. There may be periods of intermittent slowing noted in the anterior temporal EEG derivations that become prominent during sleep and hyperventilation and are suggestive of focal cerebral dysfunction. Sometimes the focal slowing can be more robust and manifests as temporal intermittent rhythmic delta activity (TIRDA).[11][4]

In addition to slowing, the classic interictal EEG abnormality in MTLE are spikes or sharp waves which phase reverse over the anterior temporal regions. The dipole orientation of these sharp waves seems to have maximum electronegativity and voltage in the basal temporal derivations (T8/T9; FT8/FT9), and electropositivity distributed widely in the contralateral centro-parietal derivations (C3/C4; P3/P4).[31][32] The sharp waves in the anterior temporal region present in the majority of patients with MTLE. [33] They tend to occur more frequently during drowsiness and early stages of sleep.[34] They become less frequent during REM sleep and are somewhat similar in frequency to that seen during awake periods.

Ictal EEG findings in patients with MTLE are unique when compared to neocortical epilepsy because of its gradual, rhythmic build-up and delayed spread to neighboring brain regions. The seizures that arise from the hippocampus usually spread to the basal temporal regions. Therefore, the use of sphenoidal electrodes can be very useful in picking up the ictal onset in many of the cases with this seizure type. The characteristic pattern seen at the onset of an MTL seizure is a rhythmic theta activity starting in the anterior/anterior-inferior temporal or sphenoidal electrode contacts with gradual spread to the lateral temporal, insular, and frontal regions.[32] An important localizing feature that can sometimes present is the occurrence of diffuse EEG attenuation and cessation of interictal epileptiform discharges (IEDs) at the onset of the seizure.[35] Shortly after the onset, a slower rhythmic theta build-up or organized spiking is noted, which gradually evolves in frequency and amplitude until the seizure spreads to neighboring brain regions followed by spread to the contralateral hemisphere. When the EEG onset precedes the clinical onset, the localization of the seizure onset to the ipsilateral hemisphere is close to 95%.[36] Finally, studies have found that postictal slowing is an important lateralizing feature in up to 70% of the cases.[11][32]

In contrast, an ictal onset with unilateral delta slowing and repetitive interictal spiking is less likely to be arising from the mesial temporal region.[32][37] Also, seizure onset with bilateral rhythmic activity and delayed evolution into a temporal pattern is a poor indicator of seizures arising from the mesial temporal region.[36]

Invasive Electroencephalogram

The use of invasive intracranial recordings using subdural grids or intracerebral depth electrodes has improved our diagnostic precision in the identification of the seizure focus. Although MTLE primarily involves the temporal lobes, the abnormal network is known to have widespread extra-temporal connectivity. It is essential to rule out other potential nodes in the network that can be independently epileptogenic. Stereo-electroencephalography (SEEG) is an important tool that registers electrical activity from very confined deep-seated brain regions that usually escape detection by usual surface recording modalities.[38] Complex signal processing techniques have been employed to understand the intrinsic properties of epileptogenic networks from electrophysiologic signals obtained from SEEG data.[39]

Unlike in scalp recording, the ictal activity recorded from intracranial electrodes detects a largely focal or regional fast beta or gamma rhythm. The focality of the rhythm on depth recording is directly proportional to the degree of hippocampal pathology.[40]

Treatment / Management

The first-line therapy for MTLE includes the initiation of appropriately chosen antiepileptic drug (AED) treatment. For patients with MTLE, the most effective AEDs are those used to treat focal epilepsies such as carbamazepine, oxcarbazepine, levetiracetam, lamotrigine, and topiramate.[41] These agents can be monotherapy or, more often, in combination to achieve adequate seizure freedom. However, it is well known that patients with MTLE often have an inadequate response to antiepileptic drug therapy.[25] Some patients who initially respond may also end up becoming medically refractory within a few years. Non-pharmacological approaches eventually play an essential role in the management of patients with medically refractory or drug-resistant MTLE. These include both surgical and neurostimulation approaches.

Surgical approaches for MTLE include open resection and other minimally invasive techniques. Standard open resective surgery is considered to be the most effective and safe treatment option for TLE with superiority to prolonged medical therapy in terms of long-term outcomes.[42] Several surgical procedures have been employed, including standard anterior temporal lobectomy, anteromedial temporal lobectomy, selective amygdalohippocampectomy, and temporal pole resection. Resective therapy has demonstrated an excellent outcome, especially if done early.[4][11] Surgical resection offers postoperative seizure freedom at two years in 60% to 80% of patients with drug-resistant MTLE, whereas longer-term follow-ups present less favorable results.[43][44] Anterior temporal lobectomy is generally safe, and the most common neurologic complication following such resective epilepsy surgery is a minor visual field deficit.

Advances in our understanding of epileptic networks have improved our ability to define the epileptogenic zone in patients with epilepsy better. The aim of disrupting epileptic networks with the smallest possible surgical lesion has led to the development of minimally invasive surgical techniques for epilepsy.[45] Minimally invasive techniques include stereotactic radiosurgery (SRS), stereotactic radiofrequency thermocoagulation (SRT), laser interstitial thermal therapy (LITT), and MRI-guided focused ultrasound ablation (FUS). SRS using gamma knife and Cyberknife deliver ionizing radiation to a focal target of mesial temporal structures in MTLE and have shown comparable postoperative seizure freedom when compared to invasive surgery.[46] Similarly, stereo-EEG (SEEG) guided thermocoagulation and laser interstitial thermal therapy (LITT) have also shown promising new developments and have been employed as alternative options to standard resective surgery.[47][48][47]

Neurostimulation for the treatment of epilepsy includes vagus nerve stimulation (VNS) responsive neurostimulation (RNS), and deep brain stimulation (DBS).[49][50][51] These are generally reserved for patients who are either not candidates for resective surgery or unwilling to undergo surgery. RNS can be used for patients with bitemporal seizure foci or foci Involving eloquent brain regions. Neurostimulation also could be an option for patients who have seizure recurrence following surgery. In patients with bitemporal epilepsy, long-term ECoG data from the RNS system can provide information enabling identification if one temporal lobe responsible for the majority of the seizures in certain patients; if so, resective surgery may be a consideration in such patients.  

Apart from seizure management, patients with MTLE may have cognitive problems, psychiatric comorbidities, and psychosocial issues. A comprehensive approach to manage an individual with MTLE must take into account the cognitive and psychiatric comorbidities that often accompany this condition.[52]

Differential Diagnosis

The seizures in patients with MTLE share semiological characteristics with other types of epilepsies, such as absence seizures, insular seizures, and occipital lobe seizures. Patients with absence seizures also manifest with a blank stare and may have subtle automatisms which can mimic seizures of MTLE.[53] Patients with seizures arising from the insula can sometimes present in a very similar manner to TLE in terms of epigastric aura and oro-alimentary automatisms.[54] Some patients with occipital lobe epilepsy have seizures that rapidly spread anteriorly to the temporal lobes and can produce semiology very similar to TLE.[55] 

Further, other medical conditions may mimic temporal lobe seizures such as panic attacks, tardive dyskinesia, excessive daytime sleepiness, periodic limb movement disorder, transient psychotic episodes, and psychogenic non-epileptic seizures (PNES).[56] These need to be differentiated using clinical and diagnostic tools such as video-EEG monitoring.

Enhancing Healthcare Team Outcomes

Medial temporal lobe epilepsy (MTLE) is the most common type of epilepsy that often becomes drug-resistant, requiring the need for referral to a comprehensive epilepsy center. Management of patients with pharmacoresistant MTLE is considered to be appropriate when carried out at a comprehensive level 3/4 epilepsy centers as recommended by the American Academy of Neurology (AAN) Epilepsy Quality Measurement Set.[57] These centers are equipped with diagnostic modalities, including video-EEG and multimodal neuroimaging capability, for evaluation of drug-resistant epilepsy. They employ an interprofessional team of specialists, including epileptologists, neurosurgeons, neuroradiologists, nuclear medicine specialists, clinical neuropsychologists, neuropathologists, and psychiatrists who can address all the different aspects of care that are needed to be provided to these patients. After performing a comprehensive evaluation, the team meets at a conference to pool all the available information about the patient and come up with an appropriate management plan. Some patients who are thought to have drug-resistant epilepsy may not have epilepsy. For others who are determined to have focal onset epilepsy, the potential surgical candidates are identified.[58] 

Epilepsy centers are still underutilized, resulting in suboptimal management of patients with drug-resistant epilepsy, including MTLE. Any patient with epilepsy who have failed a trial of two antiepileptic medication (appropriately chosen for the seizure type/epilepsy syndrome) is considered to have drug-resistant epilepsy and should receive a referral to a comprehensive epilepsy center.[59] Early referral to a comprehensive epilepsy center can provide the patient with the best opportunity for optimal seizure control and potential seizure freedom. It can also prevent psychosocial trauma, reduce the number of disability-associated life years, improve quality of life, and decrease the risk of sudden unexpected death in epilepsy patients (SUDEP).[60]

Neuroscience nurses are often involved in the care of these patients, providing monitoring, family and patient education, and facilitating evaluation and communication. Pharmacists counsel patients and families about the importance of compliance and potential side effects, verify dosing/titration and consult with the prescriber regarding agent selection. These examples of interprofessional interaction can lead to improved patient outcomes. [Level 5]

Article Details

Article Author

Chetan S. Nayak

Article Editor:

Susanta Bandyopadhyay


5/29/2022 11:45:17 PM



Blair RD, Temporal lobe epilepsy semiology. Epilepsy research and treatment. 2012;     [PubMed PMID: 22957241]


GIBBS EL,GIBBS FA,FUSTER B, Psychomotor epilepsy. Archives of neurology and psychiatry. 1948 Oct;     [PubMed PMID: 18111213]


Feindel W, The contributions of Wilder Penfield to the functional anatomy of the human brain. Human neurobiology. 1982;     [PubMed PMID: 6764468]


Tatum WO 4th, Mesial temporal lobe epilepsy. Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society. 2012 Oct;     [PubMed PMID: 23027091]


Berkovic SF,McIntosh A,Howell RA,Mitchell A,Sheffield LJ,Hopper JL, Familial temporal lobe epilepsy: a common disorder identified in twins. Annals of neurology. 1996 Aug;     [PubMed PMID: 8773604]


Hedera P,Blair MA,Andermann E,Andermann F,D'Agostino D,Taylor KA,Chahine L,Pandolfo M,Bradford Y,Haines JL,Abou-Khalil B, Familial mesial temporal lobe epilepsy maps to chromosome 4q13.2-q21.3. Neurology. 2007 Jun 12;     [PubMed PMID: 17377072]


Crompton DE,Scheffer IE,Taylor I,Cook MJ,McKelvie PA,Vears DF,Lawrence KM,McMahon JM,Grinton BE,McIntosh AM,Berkovic SF, Familial mesial temporal lobe epilepsy: a benign epilepsy syndrome showing complex inheritance. Brain : a journal of neurology. 2010 Nov;     [PubMed PMID: 20864493]


Blumcke I,Spreafico R,Haaker G,Coras R,Kobow K,Bien CG,Pfäfflin M,Elger C,Widman G,Schramm J,Becker A,Braun KP,Leijten F,Baayen JC,Aronica E,Chassoux F,Hamer H,Stefan H,Rössler K,Thom M,Walker MC,Sisodiya SM,Duncan JS,McEvoy AW,Pieper T,Holthausen H,Kudernatsch M,Meencke HJ,Kahane P,Schulze-Bonhage A,Zentner J,Heiland DH,Urbach H,Steinhoff BJ,Bast T,Tassi L,Lo Russo G,Özkara C,Oz B,Krsek P,Vogelgesang S,Runge U,Lerche H,Weber Y,Honavar M,Pimentel J,Arzimanoglou A,Ulate-Campos A,Noachtar S,Hartl E,Schijns O,Guerrini R,Barba C,Jacques TS,Cross JH,Feucht M,Mühlebner A,Grunwald T,Trinka E,Winkler PA,Gil-Nagel A,Toledano Delgado R,Mayer T,Lutz M,Zountsas B,Garganis K,Rosenow F,Hermsen A,von Oertzen TJ,Diepgen TL,Avanzini G, Histopathological Findings in Brain Tissue Obtained during Epilepsy Surgery. The New England journal of medicine. 2017 Oct 26;     [PubMed PMID: 29069555]


Tassi L,Meroni A,Deleo F,Villani F,Mai R,Russo GL,Colombo N,Avanzini G,Falcone C,Bramerio M,Citterio A,Garbelli R,Spreafico R, Temporal lobe epilepsy: neuropathological and clinical correlations in 243 surgically treated patients. Epileptic disorders : international epilepsy journal with videotape. 2009 Dec;     [PubMed PMID: 19945931]


Al Sufiani F,Ang LC, Neuropathology of temporal lobe epilepsy. Epilepsy research and treatment. 2012;     [PubMed PMID: 22957233]


French JA,Williamson PD,Thadani VM,Darcey TM,Mattson RH,Spencer SS,Spencer DD, Characteristics of medial temporal lobe epilepsy: I. Results of history and physical examination. Annals of neurology. 1993 Dec;     [PubMed PMID: 8250525]


Harvey AS,Grattan-Smith JD,Desmond PM,Chow CW,Berkovic SF, Febrile seizures and hippocampal sclerosis: frequent and related findings in intractable temporal lobe epilepsy of childhood. Pediatric neurology. 1995 Apr     [PubMed PMID: 7619185]


Lewis DV,Shinnar S,Hesdorffer DC,Bagiella E,Bello JA,Chan S,Xu Y,MacFall J,Gomes WA,Moshé SL,Mathern GW,Pellock JM,Nordli DR Jr,Frank LM,Provenzale J,Shinnar RC,Epstein LG,Masur D,Litherland C,Sun S, Hippocampal sclerosis after febrile status epilepticus: the FEBSTAT study. Annals of neurology. 2014 Feb;     [PubMed PMID: 24318290]


Blümcke I,Coras R,Miyata H,Ozkara C, Defining clinico-neuropathological subtypes of mesial temporal lobe epilepsy with hippocampal sclerosis. Brain pathology (Zurich, Switzerland). 2012 May;     [PubMed PMID: 22497612]


Liu TT,Ye XL,Zhang JP,Yu TT,Cheng SS,Zou XC,Xu Y,Chen GQ,Yin ZY, Increased adult neurogenesis associated with reactive astrocytosis occurs prior to neuron loss in a mouse model of neurodegenerative disease. CNS neuroscience     [PubMed PMID: 28960838]


Sutula T,Cascino G,Cavazos J,Parada I,Ramirez L, Mossy fiber synaptic reorganization in the epileptic human temporal lobe. Annals of neurology. 1989 Sep;     [PubMed PMID: 2508534]


Becker AJ,Chen J,Zien A,Sochivko D,Normann S,Schramm J,Elger CE,Wiestler OD,Blümcke I, Correlated stage- and subfield-associated hippocampal gene expression patterns in experimental and human temporal lobe epilepsy. The European journal of neuroscience. 2003 Nov;     [PubMed PMID: 14656328]


Houser CR, Granule cell dispersion in the dentate gyrus of humans with temporal lobe epilepsy. Brain research. 1990 Dec 10;     [PubMed PMID: 1705855]


Barkovich AJ,Guerrini R,Kuzniecky RI,Jackson GD,Dobyns WB, A developmental and genetic classification for malformations of cortical development: update 2012. Brain : a journal of neurology. 2012 May;     [PubMed PMID: 22427329]


Crino PB, Focal Cortical Dysplasia. Seminars in neurology. 2015 Jun     [PubMed PMID: 26060899]


Thom M,Blümcke I,Aronica E, Long-term epilepsy-associated tumors. Brain pathology (Zurich, Switzerland). 2012 May;     [PubMed PMID: 22497610]


Blümcke I,Aronica E,Becker A,Capper D,Coras R,Honavar M,Jacques TS,Kobow K,Miyata H,Mühlebner A,Pimentel J,Söylemezoğlu F,Thom M, Low-grade epilepsy-associated neuroepithelial tumours - the 2016 WHO classification. Nature reviews. Neurology. 2016 Dec;     [PubMed PMID: 27857123]


Fisher RS,Cross H,D'Souza C,French JA,Haut S,Higurashi N,Hirsch E,Jansen FE,Peltola J,Moshé SL,Perucca E,Lagae L,Roulet-Perez E,Schulze-Bonhage A,Scheffer IE,Somerville E,Sperling MR,Wiebe S,Yacubian EM,Zuberi S, 2017 International League Against Epilepsy classifications of seizures and epilepsy are steps in the right direction. Epilepsia. 2019 Jun;     [PubMed PMID: 31074833]


Baulac M, MTLE with hippocampal sclerosis in adult as a syndrome. Revue neurologique. 2015 Mar     [PubMed PMID: 25727907]


Pohlen MS,Jin J,Tobias RS,Maheshwari A, Pharmacoresistance with newer anti-epileptic drugs in mesial temporal lobe epilepsy with hippocampal sclerosis. Epilepsy research. 2017 Nov;     [PubMed PMID: 28941835]


Panzica F,Varotto G,Rotondi F,Spreafico R,Franceschetti S, Identification of the Epileptogenic Zone from Stereo-EEG Signals: A Connectivity-Graph Theory Approach. Frontiers in neurology. 2013 Nov 6;     [PubMed PMID: 24223569]


Ercan K,Gunbey HP,Bilir E,Zan E,Arslan H, Comparative Lateralizing Ability of Multimodality MRI in Temporal Lobe Epilepsy. Disease markers. 2016;     [PubMed PMID: 27974864]


Peter J,Houshmand S,Werner TJ,Rubello D,Alavi A, Novel assessment of global metabolism by 18F-FDG-PET for localizing affected lobe in temporal lobe epilepsy. Nuclear medicine communications. 2016 Aug     [PubMed PMID: 27092666]


Amorim BJ,Ramos CD,dos Santos AO,de Lima Mda C,Min LL,Camargo EE,Cendes F,Etchebehere EC, Brain SPECT in mesial temporal lobe epilepsy: comparison between visual analysis and SPM. Arquivos de neuro-psiquiatria. 2010 Apr;     [PubMed PMID: 20464277]


Cho JW,Hong SB,Lee JH,Kang JW,Lee MJ,Lee JY,Park HS,Suh M,Joo EY,Seo DW, Contralateral hyperperfusion and ipsilateral hypoperfusion by ictal SPECT in patients with mesial temporal lobe epilepsy. Epilepsy research. 2010 Feb     [PubMed PMID: 20092979]


Klass DW, Electroencephalographic manifestations of complex partial seizures. Advances in neurology. 1975;     [PubMed PMID: 1217558]


Ebersole JS,Pacia SV, Localization of temporal lobe foci by ictal EEG patterns. Epilepsia. 1996 Apr;     [PubMed PMID: 8603646]


Williamson PD,French JA,Thadani VM,Kim JH,Novelly RA,Spencer SS,Spencer DD,Mattson RH, Characteristics of medial temporal lobe epilepsy: II. Interictal and ictal scalp electroencephalography, neuropsychological testing, neuroimaging, surgical results, and pathology. Annals of neurology. 1993 Dec;     [PubMed PMID: 8250526]


Yu-Dan L,Zan W,Ma DH,Meng HM,Cui L, Association between epileptiform discharges and the sleep cycle in 200 epileptic patients. The International journal of neuroscience. 2013 Mar     [PubMed PMID: 23134467]


Murro AM,Park YD,King DW,Gallagher BB,Smith JR,Yaghmai F,Toro V,Figueroa RE,Loring DW,Littleton W, Seizure localization in temporal lobe epilepsy: a comparison of scalp-sphenoidal EEG and volumetric MRI. Neurology. 1993 Dec;     [PubMed PMID: 8255452]


Risinger MW,Engel J Jr,Van Ness PC,Henry TR,Crandall PH, Ictal localization of temporal lobe seizures with scalp/sphenoidal recordings. Neurology. 1989 Oct;     [PubMed PMID: 2797451]


Tao JX,Ray A,Hawes-Ebersole S,Ebersole JS, Intracranial EEG substrates of scalp EEG interictal spikes. Epilepsia. 2005 May;     [PubMed PMID: 15857432]


Gonzalez-Martinez J,Mullin J,Vadera S,Bulacio J,Hughes G,Jones S,Enatsu R,Najm I, Stereotactic placement of depth electrodes in medically intractable epilepsy. Journal of neurosurgery. 2014 Mar;     [PubMed PMID: 24405074]


Wang MY,Wang J,Zhou J,Guan YG,Zhai F,Liu CQ,Xu FF,Han YX,Yan ZF,Luan GM, Identification of the epileptogenic zone of temporal lobe epilepsy from stereo-electroencephalography signals: A phase transfer entropy and graph theory approach. NeuroImage. Clinical. 2017;     [PubMed PMID: 28794979]


Vossler DG,Kraemer DL,Haltiner AM,Rostad SW,Kjos BO,Davis BJ,Morgan JD,Caylor LM, Intracranial EEG in temporal lobe epilepsy: location of seizure onset relates to degree of hippocampal pathology. Epilepsia. 2004 May;     [PubMed PMID: 15101831]


Marson AG,Al-Kharusi AM,Alwaidh M,Appleton R,Baker GA,Chadwick DW,Cramp C,Cockerell OC,Cooper PN,Doughty J,Eaton B,Gamble C,Goulding PJ,Howell SJ,Hughes A,Jackson M,Jacoby A,Kellett M,Lawson GR,Leach JP,Nicolaides P,Roberts R,Shackley P,Shen J,Smith DF,Smith PE,Smith CT,Vanoli A,Williamson PR, The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial. Lancet (London, England). 2007 Mar 24;     [PubMed PMID: 17382827]


Wiebe S,Blume WT,Girvin JP,Eliasziw M, A randomized, controlled trial of surgery for temporal-lobe epilepsy. The New England journal of medicine. 2001 Aug 2;     [PubMed PMID: 11484687]


Arruda F,Cendes F,Andermann F,Dubeau F,Villemure JG,Jones-Gotman M,Poulin N,Arnold DL,Olivier A, Mesial atrophy and outcome after amygdalohippocampectomy or temporal lobe removal. Annals of neurology. 1996 Sep;     [PubMed PMID: 8797534]


de Tisi J,Bell GS,Peacock JL,McEvoy AW,Harkness WF,Sander JW,Duncan JS, The long-term outcome of adult epilepsy surgery, patterns of seizure remission, and relapse: a cohort study. Lancet (London, England). 2011 Oct 15;     [PubMed PMID: 22000136]


Quigg M,Harden C, Minimally invasive techniques for epilepsy surgery: stereotactic radiosurgery and other technologies. Journal of neurosurgery. 2014 Dec;     [PubMed PMID: 25434958]


Feng ES,Sui CB,Wang TX,Sun GL, Stereotactic radiosurgery for the treatment of mesial temporal lobe epilepsy. Acta neurologica Scandinavica. 2016 Dec;     [PubMed PMID: 26846702]


Fan X,Shan Y,Lu C,An Y,Wang Y,Du J,Wang D,Wei P,Fisher RS,Wang Y,Ren L,Zhao G, Optimized SEEG-guided radiofrequency thermocoagulation for mesial temporal lobe epilepsy with hippocampal sclerosis. Seizure. 2019 Oct;     [PubMed PMID: 31521052]


Wicks RT,Jermakowicz WJ,Jagid JR,Couture DE,Willie JT,Laxton AW,Gross RE, Laser Interstitial Thermal Therapy for Mesial Temporal Lobe Epilepsy. Neurosurgery. 2016 Dec;     [PubMed PMID: 27861328]


Alsaadi TM,Laxer KD,Barbaro NM,Marks WJ Jr,Garcia PA, Vagus nerve stimulation for the treatment of bilateral independent temporal lobe epilepsy. Epilepsia. 2001 Jul;     [PubMed PMID: 11488900]


Jobst BC,Kapur R,Barkley GL,Bazil CW,Berg MJ,Bergey GK,Boggs JG,Cash SS,Cole AJ,Duchowny MS,Duckrow RB,Edwards JC,Eisenschenk S,Fessler AJ,Fountain NB,Geller EB,Goldman AM,Goodman RR,Gross RE,Gwinn RP,Heck C,Herekar AA,Hirsch LJ,King-Stephens D,Labar DR,Marsh WR,Meador KJ,Miller I,Mizrahi EM,Murro AM,Nair DR,Noe KH,Olejniczak PW,Park YD,Rutecki P,Salanova V,Sheth RD,Skidmore C,Smith MC,Spencer DC,Srinivasan S,Tatum W,Van Ness P,Vossler DG,Wharen RE Jr,Worrell GA,Yoshor D,Zimmerman RS,Skarpaas TL,Morrell MJ, Brain-responsive neurostimulation in patients with medically intractable seizures arising from eloquent and other neocortical areas. Epilepsia. 2017 Jun;     [PubMed PMID: 28387951]


Jin H,Li W,Dong C,Wu J,Zhao W,Zhao Z,Ma L,Ma F,Chen Y,Liu Q, Hippocampal deep brain stimulation in nonlesional refractory mesial temporal lobe epilepsy. Seizure. 2016 Apr;     [PubMed PMID: 26908151]


Mula M,Sander JW, Psychosocial aspects of epilepsy: a wider approach. BJPsych open. 2016 Jul;     [PubMed PMID: 27703786]


Hurst R,Chiota-McCollum N,Tatum W, Adult absence semiology misinterpreted as mesial temporal lobe epilepsy. Epileptic disorders : international epilepsy journal with videotape. 2014 Dec;     [PubMed PMID: 25465725]


Ryvlin P, Avoid falling into the depths of the insular trap. Epileptic disorders : international epilepsy journal with videotape. 2006 Aug;     [PubMed PMID: 17012071]


Appel S,Sharan AD,Tracy JI,Evans J,Sperling MR, A comparison of occipital and temporal lobe epilepsies. Acta neurologica Scandinavica. 2015 Oct;     [PubMed PMID: 25809072]


Dickinson P,Looper KJ, Psychogenic nonepileptic seizures: a current overview. Epilepsia. 2012 Oct     [PubMed PMID: 22882112]


Patel AD,Baca C,Franklin G,Herman ST,Hughes I,Meunier L,Moura LMVR,Munger Clary H,Parker-McFadden B,Pugh MJ,Schultz RJ,Spanaki MV,Bennett A,Josephson SA, Quality improvement in neurology: Epilepsy Quality Measurement Set 2017 update. Neurology. 2018 Oct 30;     [PubMed PMID: 30282773]


Bayer AD,Blum AS,Asaad WF,Roth J,Toms SA,Deck GM, Fighting Fire with Fire: Surgical Options for Patients with Drug-Resistant Epilepsy. Rhode Island medical journal (2013). 2018 Mar 1;     [PubMed PMID: 29490324]


Kwan P,Arzimanoglou A,Berg AT,Brodie MJ,Allen Hauser W,Mathern G,Moshé SL,Perucca E,Wiebe S,French J, Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia. 2010 Jun;     [PubMed PMID: 19889013]


Engel J Jr, What can we do for people with drug-resistant epilepsy? The 2016 Wartenberg Lecture. Neurology. 2016 Dec 6;     [PubMed PMID: 27920283]