Temporal lobe epilepsy

Temporal lobe epilepsy

Mesial temporal sclerosis (MTS) is the most common cause of intractable temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is a chronic neurological condition characterized by recurrent seizures (epilepsy) which originate in the temporal lobe with progressive neurological disabilities, including cognitive deficitanxiety and depression.

The seizures involve sensory changes, for example smelling an unusual odour that is not there, and disturbance of memory.

Based on the promising results of randomized controlled trials, deep brain stimulation (DBS) and responsive neurostimulation (RNS) are increasingly used in the treatment of patients with drug-resistant epilepsy. Drug-resistant temporal lobe epilepsy (TLE) is an indication of either DBS of the anterior nucleus of the thalamus (ANT) or temporal lobe (TL) RNS, but there are no studies that directly compare seizure benefits and adverse effects associated with these therapies in this patient population.

Mesial temporal lobe epilepsy.

Neocortical temporal lobe epilepsy

Unilateral temporal lobe epilepsy

Sixty patients with drug-resistant temporal lobe epilepsy who underwent anterior temporal lobectomy were enrolled. Anterior hippocampal samples were collected after surgery and analyzed by immunofluorescence (n = 7/group). They also evaluated the expression of HMGB1 in TLE patients with hippocampal sclerosis and measured the level of plasma HMGB1 by enzyme-linked immunosorbent assay. The results showed that 28.3% of the patients (17/60) had comorbid depression. HMGB1 was ubiquitously expressed in all subregions of the anterior hippocampus. The ratio of HMGB1-immunoreactive neurons and astrocytes was significantly increased in both TLE patients with hippocampal sclerosis and TLE patients with comorbid depression compared to patients with TLE only. The ratio of cytoplasmic to nuclear HMGB1-positive neurons in the hippocampus was higher in depressed patients with TLE than in non-depressed patients, which suggested that more HMGB1 translocated from the nucleus to the cytoplasm in the depressed group. There was no significant difference in the plasma level of HMGB1 among patients with TLE alone, TLE with hippocampal sclerosis, and TLE with comorbid depression. The results of the study revealed that the translocation of HMGB1 from the nucleus to the cytoplasm in hippocampal neurons may play a previously unrecognized role in the initiation and amplification of epilepsy and comorbid depression. The direct targeting of neural HMGB1 is a promising approach for anti-inflammatory therapy 1)


Yang et al., therefore, examined all patients who underwent ANT-DBS or TL-RNS for drug-resistant TLE.

They performed a retrospective review of patients who were treated with either ANT-DBS or TL-RNS for drug-resistant TLE with at least 12 months of follow-up. Along with the clinical characteristics of each patient’s epilepsyseizure frequency was recorded throughout each patient’s postoperative clinical course.

26 patients underwent ANT-DBS implantation, and 32 patients underwent TL-RNS for drug-resistant TLE. Epilepsy characteristics of both groups were similar. Patients who underwent ANT-DBS demonstrated a median seizure reduction of 58% at 12-15 months, compared to a median seizure reduction of 70% at 12-15 months in patients treated with TL-RNS (p > 0.05). The responder rate (percentage of patients with a 50% decrease or more in seizure frequency) was 54% for ANT-DBS and 56% for TL-RNS (p > 0.05). Incidence of complications and stimulation-related side effects did not significantly differ between therapies.

They demonstrated in a single-center experience that patients with drug-resistant TLE benefit similarly from either ANT-DBS or TL-RNS. Selection of either ANT-DBS or TL-RNS may therefore depend more heavily on patient and provider preference, as each has unique capabilities and configurations. Future studies will consider subgroup analyses to determine if specific patients have greater seizure frequency reduction from one form of neuromodulation strategy over another 2).


1)

Li XL, Wang S, Tang CY, Ma HW, Cheng ZZ, Zhao M, Sun WJ, Wang XF, Wang MY, Li TF, Qi XL, Zhou J, Luan GM, Guan YG. Translocation of High Mobility Group Box 1 From the Nucleus to the Cytoplasm in Depressed Patients With Epilepsy. ASN Neuro. 2022 Jan-Dec;14:17590914221136662. doi: 10.1177/17590914221136662. PMID: 36383501.
2)

Yang JC, Bullinger KL, Dickey AS, Karakis I, Alwaki A, Cabaniss BT, Winkel D, Rodriguez-Ruiz A, Willie JT, Gross RE. Anterior Nucleus of the Thalamus Deep Brain Stimulation Versus Temporal Lobe Responsive Neurostimulation for Temporal Lobe Epilepsy. Epilepsia. 2022 Jun 15. doi: 10.1111/epi.17331. Epub ahead of print. PMID: 35704344.

Epilepsy diagnosis

Epilepsy diagnosis

The accurate diagnosis of seizures is essential as some patients will be misdiagnosed with epilepsy, whereas others will receive an incorrect diagnosis. Indeed, errors in diagnosis are common, and many patients fail to receive the correct treatment, which often has severe consequences

Imaging is pivotal in the evaluation and management of patients with seizure disorders.

Positron emission tomography (PET) is the most commonly performed interictal functional neuroimaging technique that may reveal a focal hypometabolic region concordant with seizure onset. Single photon emission computed tomography (SPECT) studies may assist the performance of ictal neuroimaging in patients with pharmacoresistant focal epilepsy being considered for neurosurgical treatment 1).

Elegant structural neuroimaging with magnetic resonance imaging (MRI) may assist in determining the etiology of focal epilepsy and demonstrating the anatomical changes associated with seizure activity. The high diagnostic yield of MRI to identify the common pathological findings in individuals with focal seizures including mesial temporal sclerosis, vascular anomalies, Low-grade glioma and malformations of cortical development has been demonstrated.

Positron emission tomography (PET) imaging in epilepsy is an in vivo technique that allows the localization of a possible seizure onset zone (SOZ) during the interictal period. Stereo-electro-encephalography (SEEG) is the gold standard to define the SOZ. The objective of aresearch was to evaluate the accuracy of PET imaging in localizing the site of SOZ compared with SEEG.

Seven patients with refractory temporal lobe epilepsy (Ep) and 2 healthy controls (HC) underwent 2 PET scans, one with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) and another with 2′-[18F]fluoroflumazenil (FFMZ), acquired 1 day apart. FDG was acquired for 10 min (static scan) 1 h after administration. An FFMZ scan was acquired for 60 min from radiopharmaceutical administration in a dynamic mode. Each brain PET image was segmented using a standard template implemented in PMOD 3.8. The pons was used as the reference region for modeling of the nondisplaceable binding potential (BPND)for FFMZ, and to obtain uptake ratios for FDG. SEEG studies of patients were performed as a part of their surgical evaluation to define the SOZ.

Well-defined differences between HC and Ep were found with both radiopharmaceuticals, showing the utility to identify abnormal brain regions using quantitative PET imaging. Lateralization of the SOZ findings by PET (lower uptake/binding in a specific brain hemisphere) matched in 86% for FFMZ and 71% for FDG with SEEG data.

Quantitative PET imaging is an excellent complementary tool that matches reasonably well with SEEG to define SOZ in presurgical evaluation 2).

Cerebrospinal fluid analysis for epilepsy

Automatic seizure detection.

Results of a cross-sectional study suggest that genetic testing of individuals with epilepsy may be materially associated with clinical decision-making and improved patient outcome3).


1)

Cendes F, Theodore WH, Brinkmann BH, Sulc V, Cascino GD. Neuroimaging of epilepsy. Handb Clin Neurol. 2016;136:985-1014. doi: 10.1016/B978-0-444-53486-6.00051-X. PubMed PMID: 27430454.
2)

Avendaño-Estrada A, Velasco F, Velasco AL, Cuellar-Herrera M, Saucedo-Alvarado PE, Marquez-Franco R, Rivera-Bravo B, Ávila-Rodríguez MA. Quantitative Analysis of [18F]FFMZ and [18F]FDG PET Studies in the Localization of Seizure Onset Zone in Drug-Resistant Temporal Lobe Epilepsy. Stereotact Funct Neurosurg. 2019 Nov 13:1-9. doi: 10.1159/000503692. [Epub ahead of print] PubMed PMID: 31722358.
3)

McKnight D, Morales A, Hatchell KE, Bristow SL, Bonkowsky JL, Perry MS, Berg AT, Borlot F, Esplin ED, Moretz C, Angione K, Ríos-Pohl L, Nussbaum RL, Aradhya S; ELEVIATE Consortium, Haldeman-Englert CR, Levy RJ, Parachuri VG, Lay-Son G, de Montellano DJD, Ramirez-Garcia MA, Benítez Alonso EO, Ziobro J, Chirita-Emandi A, Felix TM, Kulasa-Luke D, Megarbane A, Karkare S, Chagnon SL, Humberson JB, Assaf MJ, Silva S, Zarroli K, Boyarchuk O, Nelson GR, Palmquist R, Hammond KC, Hwang ST, Boutlier SB, Nolan M, Batley KY, Chavda D, Reyes-Silva CA, Miroshnikov O, Zuccarelli B, Amlie-Wolf L, Wheless JW, Seinfeld S, Kanhangad M, Freeman JL, Monroy-Santoyo S, Rodriguez-Vazquez N, Ryan MM, Machie M, Guerra P, Hassan MJ, Candee MS, Bupp CP, Park KL, Muller E 2nd, Lupo P, Pedersen RC, Arain AM, Murphy A, Schatz K, Mu W, Kalika PM, Plaza L, Kellogg MA, Lora EG, Carson RP, Svystilnyk V, Venegas V, Luke RR, Jiang H, Stetsenko T, Dueñas-Roque MM, Trasmonte J, Burke RJ, Hurst ACE, Smith DM, Massingham LJ, Pisani L, Costin CE, Ostrander B, Filloux FM, Ananth AL, Mohamed IS, Nechai A, Dao JM, Fahey MC, Aliu E, Falchek S, Press CA, Treat L, Eschbach K, Starks A, Kammeyer R, Bear JJ, Jacobson M, Chernuha V, Meibos B, Wong K, Sweney MT, Espinoza AC, Van Orman CB, Weinstock A, Kumar A, Soler-Alfonso C, Nolan DA, Raza M, Rojas Carrion MD, Chari G, Marsh ED, Shiloh-Malawsky Y, Parikh S, Gonzalez-Giraldo E, Fulton S, Sogawa Y, Burns K, Malets M, Montiel Blanco JD, Habela CW, Wilson CA, Guzmán GG, Pavliuk M. Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice. JAMA Neurol. 2022 Oct 31. doi: 10.1001/jamaneurol.2022.3651. Epub ahead of print. PMID: 36315135.

Epilepsy surgery indications

Epilepsy surgery indications

Epilepsy surgery is an established safe and effective treatment for selected candidates with drug-resistant epilepsy. In a opinion piece, Hale et al. from the Children’s of Alabama, Great Ormond Street Hospital, Nemours Children’s Hospital outlined the clinical and experimental evidence for selectively considering epilepsy surgery prior to drug resistance. The rationale for expedited surgery is based on the observations that, 1) a high proportion of patients with lesional epilepsies (e.g. focal cortical dysplasia, epilepsy associated tumours) will progress to drug-resistance, 2) surgical treatment of these lesions, especially in non-eloquent areas of brain, is safe, and 3) earlier surgery may be associated with better seizure outcomes. Potential benefits beyond seizure reduction or elimination include less exposure to anticonvulsants (ASM), which may lead to improved developmental trajectories in children and optimize long-term neurocognitive outcomes and quality of life. Further, there exists emerging experimental evidence that brain network dysfunction exists at the onset of epilepsy, where continuing dysfunctional activity could exacerbate network perturbations. This in turn could lead to expanded seizure foci and contribution to the comorbidities associated with epilepsy. Taken together, they rationalize that epilepsy surgery, in carefully selected cases, may be considered prior to drug resistance. Lastly, they outlined the path forward, including the challenges associated with developing the evidence base and implementing this paradigm into clinical care 1).


20% of patients continue to have seizures despite aggressive medical management with antiepileptic drugs AEDs. Many of these patients may be candidates for surgical procedures to control their seizures 2).

Seizure disorder must be severe, medically refractory with satisfactory trials of tolerable medication for at least 1 year, and disabling to the patient. Medically refractory epilepsy is usually considered two attempts of high-dose monotherapy with two distinct AEDs, and one attempt at polytherapy.

The three general categories of patients suitable for seizure surgery have 3):

  1. partial seizures

a) temporal origin: the largest group of surgical candidates (especially mesial temporal lobe epilepsy (MTLE) which is often medically refractory)

b) extratemporal origin

  1. symptomatic generalized seizures: e.g. Lennox-Gastaut syndrome.

  2. unilateral, multifocal epilepsy associated with infantile hemiplegia syndrome.


The goal is to eliminate seizures or significantly reduce seizure burden.

In most state-of-the-art epilepsy units, resective epilepsy surgery is currently the standard treatment for intractable epilepsy. Generally, the success rate, defined as a seizure-free status or Engel class I, is between 62% and 71%, as compared to 14% in non-operated cases 4) 5).

Generally, surgery is considered in patients whose seizures cannot be controlled by adequate trials of two different medications. Epilepsy surgery has been performed for more than a century, but its use dramatically increased in the 1980s and ’90s, reflecting its efficacy in selected patients.

Patients with comorbid psychosis and temporal lobe drug-resistant epilepsy may benefit from epilepsy surgery under close psychiatric supervision 6).

Epilepsy surgery is an effective and safe therapeutic modality in childhood. In children with extratemporal epilepsy, more careful interpretation of clinical and investigative data is needed to achieve favorable seizure outcome 7).

see Tuberous sclerosis complex surgery.


1)

Hale AT, Chari A, Scott RC, Cross JH, Rozzelle CJ, Blount JP, Tisdall MM. Expedited epilepsy surgery prior to drug resistance in children: a frontier worth crossing? Brain. 2022 Jul 27:awac275. doi: 10.1093/brain/awac275. Epub ahead of print. PMID: 35883201.
2)

Engel JJ. Surgery for Seizures. N Engl J Med. 1996; 334:647–652
3)

National Institutes of Health Consensus Development Conference. Surgery for Epilepsy. JAMA. 1990; 264:729–733
4)

Edelvik A, Rydenhag B, Olsson I, et al. Long-term outcomes of epilepsy surgery in Sweden: a national prospective and longitudinal study. Neurology 2013;81:1244–51.
5)

Sarkis RA, Jehi L, Najm IM, et al. Seizure outcomes following multilobar epilepsy surgery. Epilepsia 2012;53:44–50.
6)

D’Alessio L, Scévola L, Fernandez Lima M, Oddo S, Solís P, Seoane E, Kochen S. Psychiatric outcome of epilepsy surgery in patients with psychosis and temporal lobe drug-resistant epilepsy: A prospective case series. Epilepsy Behav. 2014 Jul 15;37C:165-170. doi: 10.1016/j.yebeh.2014.06.002. [Epub ahead of print] PubMed PMID: 25036902.
7)

Kim SK, Wang KC, Hwang YS, Kim KJ, Chae JH, Kim IO, Cho BK. Epilepsy surgery in children: outcomes and complications. J Neurosurg Pediatr. 2008 Apr;1(4):277-83. doi: 10.3171/PED/2008/1/4/277. PubMed PMID: 18377302.
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