Epilepsyexternal image Sept14_2010_18474187_NeuronBlueRedRotated500px_IcagenStopsEpilepsyStudy1605041912.jpg

Epilepsy is a neurological disorder characterized by the presence of seizures. A seizure is caused by hypersynchronous neuronal activity in the CNS1. Clinically, a seizure can manifest itself in a number of different ways, including convulsive body shaking, jerking, muscle twitching, or the loss of consciousness, to name a few2. About 60 million people world-wide suffer from epilepsy, including 400, 000 Canadians2.
The pathology of epilepsy is numerous, ranging from genetic to non-genetic factors. Idiopathic generalized epilepsies (IGEs) account for 1/3 of all epileptic cases and are believed to be genetic in nature3. The α7 subunit of nicotinergic acetylcholine receptor, coded by the CHRNA7 gene, is of particular interest because it is present in the reticular thalamus, believed to be the source of IGEs4. Furthermore, GLUT1 receptors, coded by the SLC2A1 gene, has also been implicated in seizure development as it affects glucose usage by reducing its maximum uptake velocity5.

One of the most common non-genetic causes of epilepsy are brain tumors. Glioma invades adjacent normal cells and interferes with surrounding microenvironment6. Excessive secretion of glutamate by glioma cells is directly responsible for seizure generation via cysteine-glutamate exchanger (SXC)6. Administration of sulfasalazine (SAS), an inhibitor of SXC, greatly reduced the hyperexcitability of epileptic tissues6. The effect of glutamate accumulation and peritumoral chemical imbalance as it relates to seizure presentation is examined in greater detail below.

Although there is no cure for epilepsy, different treatment modalities are available to control seizures, including anticonvulsant drugs, surgical treatment and electrical stimulation devices. Potassium channels and Interleukin-1 type 1 receptors/Toll-like receptors have emerged as important drug targets7,8. Nonetheless, anticonvulsant drugs are limited in their effectiveness to control seizures9. These limitations, in particular pharmacoresistance, as well as future research approaches to drug development will be examined10.

Furthermore, memory impairment is one of the most prominent cognitive deficits affiliated with epilepsy, particularly temporal lobe epilepsy (TLE). TLE induces hippocampal sclerosis, which leads to memory impairment. It is also involved in the reduction of the postcentral gyrus, causing cognitive deficits11. On the contrary, anticonvulsant drugs and psychological factors, such as mood, also contribute to memory impairments11. The implications of TLE and its treatment on memory will be further analyzed.


1. Genetic Determinants (Fangjia Lu)

1.1 Overview of Idiopathic Generalized Epilepsies

1.1.1 GABA receptors

1.1.2 Glucose transporters

1.1.3 Nicotinergic acetylcholine receptor

1.2.Neurotoxicity in Tumor Associated Epilepsy (Weixuan Qu)

1.2.1 Tumor type, Incidence Rate

1.2.2 Peritumoral Hoeostasis

1.2.3 TNF-a Triggered Immune Response

1.2.4 Altered Expression of Glutamate Receptor

1.2.5 Gutamate Excitotoxicity

2. Treatment (Mehala Subramaniapillai)

2.1 The GABAergic System

2.1.1 GABA A Receptor

2.1.2 GABA B Receptor

2.1.3 GABAergic Interneurons

2.2 Seizures

2.3 Antiepileptic Drugs

2.3.1 GABA A Agonists

2.3.2 GABA Reuptake Inhibitors

2.3.3 AED acting as GABA

2.4 GABAergic Neuronal Precursor Grafting

3. Memory (Ho Yin Bertha Cheng)

3.1 Medial Temporal Lobe Epilepsy (MTLE)

3.1.1 Characterization of Medial Temporal Lobe Epilepsy

3.1.2 Neurocognitive impairments associated with Right TLE and Left TLE

3.2 Hippocampal Sclerosis (MTLE-HS)

3.2.1 Volume of hippocampus, extratemporal structures and memory impairment

3.2.2 Effects on egocentric and allocentric memory

3.2.3 Upregulation of Type 1 cannabinoid receptor (CB1R)

3.3 Anticonvulsants

3.3.1 Benzodiazepine in relation to anterograde amnesia

3.3.2 Phenobarbital in relation to the impairment of short term memory and attention deficit

3.3.3 Topiramate in relation to verbal inarticulateness

3.4 Major Depressive Disorder

3.4.1 Serotonin 1A Receptor (5HT 1A receptor) – Decrease of binding in left hippocampus

3.4.2 Depression and Lesion Localization

Works Cited

  1. Martindale JL, Goldstein JN, Pallin DJ. Emergency department seizure epidemiology. Emerg Med Clin North Am (2011 29(1):15-27.
  2. Jacobs MP, Leblanc GG, Brooks-Kayal A, Jensen FE, Lowenstein DH, Noebels JL, Spencer DD, Swann JW. Curing epilepsy: Progress and future directions. Epilepsy Behav (2009) 14(3):438-45.
  3. Gardiner, M. Genetics of idiopathic generalized epilepsies. Epilepsia (2005)46(9):15-20.
  4. Helbig, I., et al. 15a13.3 Microdeletions increase risk of idiopathic generalized epilepsy. Nature Genetics (2009)41(2):160-162.
  5. Noebels, JL. The biology of epilepsy genes. The Annual Review of Neuroscience (2003)26:599-625.
  6. Rajneesh KF, Binder D. Tumor-associated epilepsy. Neurosurg Focus, (2009) 27(2):E4.
  7. N'Gouemo P. Targeting BK (big potassium) channels in epilepsy. Expert Opin Ther Targets (2011) 15(11):1283-95.
  8. Maroso M, Balosso S, Ravizza T, Liu J, Bianchi ME, Vezzani A. Interleukin-1 type 1 receptor/Toll-like receptor signalling in epilepsy: The importance of IL-1beta and high-mobility group box 1. J Intern Med (GBR) (2011) 270(4):319-26.
  9. Cook AM, Bensalem-Owen MK. Mechanisms of action of antiepileptic drugs. Therapy (2011) 8(3):307-13.
  10. Boison D, Masino SA, Geiger JD. Homeostatic bioenergetic network regulation: A novel concept to avoid pharmacoresistance in epilepsy. Expert Opin Drug Discov (2011) 6(7):713-24.
  11. Weniger G, Ruhleder M, Lange C, Irle E. Impaired egocentric memory and reduced somatosensory cortex size in temporal lobe epilepsy with hippocampal sclerosis. Behavioural Brain Research. (2011) 227: 116-124.