Relevant scientific research of the topic
It is made quite clear that Mr Klaerner suffers from epilepsy, and experiences generalised tonic-clonic seizures and bouts of unconsciousness. Epilepsy is a neurological disorder characterised by the brain’s increased susceptibility to seizure. The origin of seizures, behavioural manifestations, and contributing genetic mutations involved widely differ depending upon the type of epilepsy, the two most significant types being partial and generalised. Partial epilepsy is when there is a specific area of seizure onset that can be causally identified, whereas generalised epilepsy is when such a direct link to a particular system or region is not yet able to occur. Thankfully, various functional methods, such as fMRI (functional magnetic imaging), EEG (electroencephalogram) and SPECT (single positron emission topography), are becoming more available, and slowly researchers are unravelling the mystery of these seizures.
Generalised tonic-clonic seizures (GTCS) are the most dramatic and stigmatised seizures, causing a patient to go contract and flex all muscles, fall over, convulse and sometimes howl (Blumfeid et al., 2009). Seizures occur without warning and appear to have no trigger contributing to their onset (Sommerville, 2012). Despite the name, GTCS is seen in both generalised and partial epilepsies. The only difference is that partial GTCS starts in one area and spreads, thus it is called secondarily GTCS while the other is known as primary GTCS. Due to the jerking movements this seizure’s ictal state (during the seizure) many imaging techniques are useless as too much noise is present to produce reliable results.

Hrachovy & Frost (2006), outline the findings of numerous EEG studies of patients undergoing various seizures, their explanation remaining one of the most comprehensive one of EEG activity during GTCS seizures. Seizure onset is easily seen through generalised polyspike-wave closely followed by a generalised attenuation in voltage lasting a few seconds. Rhythmic activity at ~20-40Hz, this marks the beginning of the tonic phase, which reduces to ~10-12Hz (alpha frequency) and increases in amplitude as it continues. Overall the tonic phase is said to last from 8 to 10 seconds. Physically, the tonic phase is usually announced by muscle rigidity, and sometimes accompanied by the patient crying out, closely followed by falling. It should be noted that the patient is usually unconscious from the initial generalised voltage attenuation and often remains so until several minutes after the seizure apparently has ceased. The turn over to the clonic phase is marked by slower generalised activity with progressively increased amplitude and slow frequency. With time these waves become mixed in with the polyspikes that continue throughout the tonic phase, producing polyspike-wave discharges. These are thought to be indicative of rhythmic firing throughout the brain, as they are accompanied by uncontrollable muscular contractions and relaxations. As the seizure progresses these cycles become increasingly intermittent, with the last oscillation displaying normal EEG activity sustained over a few seconds. Upon seizure termination, the postictal state begins, and in GTCS the person is usually still unconscious. EEG activity at this point shows irregular delta waves at low voltage, which gradually increase in amplitude and frequency as the patient returns to baseline and recovers consciousness (Hrachovy & Frost, 2006; Seneviratne, Cook, & D’Souza, 2012).

Many researchers agree that regardless of the seizure’s origin, thalamocoritcal dysfunction is one of the classic outcomes. The hypothesis with the greatest convergent support from numerous other theories is that of altered sleep rhythm firing of thalamocortical and reticular thamalic neurons. Under normal circumstances these pathways regulate the spindle activity of the thalamus during sleep. Slow (<1 Hz) cortical oscillation includes the rhythmic firing of excitatory cortical neurons causing reticular thalamic excitation. γ-aminobutyric acid (GABA) is released by reticular thalamic excitation, resulting in inhibitory GABAA and GABAB receptor activation of thalamocortical neurons, thus hyperpolarising them and inhibiting other reticular thalamic neurons. Thalamocortical hyperpolarisation deactivates the T-type Ca2+ channels allowing for the production of regenerative calcium spikes that are also able to initiate action potentials. It is this mechanism of delayed burst rebound action potentials that then causes the thalamocortical neurons to then activate both reticular thalamic and cortical neurons, thus resulting in the synchronisation of these two areas. In the theory of hypersynchrony, reticular thalamic neurons lack a particular subunit in their GABAA receptors thus causing these neurons to fire as the thalamocortical ones do, as opposed to firing on an alternate cycle (Beenhakker & Huguenard, 2009). This is supported by the hypothesis of cortical hyperexcitibility, which poses the idea that increased excitation of specific regions of the cortex causes spike-wave discharges that are stereotypic of epilepsy. Supporting evidence is provided by the fact that Blumfeld & McCormick (2000) found that fast sparse corticothalamically delivered shocks resulted in spike wave disrcharges, but were restored by a GABA antagonist.

  1. Beenhakker, M.P., & Huguenard, J.R., (2009). Neurons that fire together also conspire together: Is normal sleep circuitry hijacked to generate epilepsy? Neuron 62(5), 612-632. Doi: 10.1016/j.neuron.2009.05.015
  2. Blumfeld, H., & McCormick, D.A., (2000). Corticothalamic inputs control the pattern of activity generated in thalamocortical networks. Journal of Neuroscience 20, 5153-5162
  3. Blumfeld, H., Varghese, G.I., Purcaro, M.J., Motellow, J.E., Enev, M., McKnally, K.A., Levin, A.R., Hirsch, L.J., Tikofsky, R., Zubal, I.G., Paige, A.L., & Spencer, S.S., (2009). Cortical and subcortical networks in human secondarily generalised tonic-clonic seizures. Brain; A Journal of Neurology, 132, 999-1012. Doi: 10.1093/brain/awp028
  4. DeSalvo, M.N., Schridde, U., Mishra, A.M., Motelow, J.E., Purcaro, J., Danielson, N., Bai, X., Hyder, F., & Blumfeld, H., (2010). Focal BOLD fMRI changes in bicuculine-induced tonic-clonic seizures in the rat. NeuroImage, 50(3), 902-909
  5. Gotman, J., Grova, C., Bagshaw, A., Kobayashi, E., Aghakhani, Y., & Dubeau, F., (2005). Generalized epileptic discharges show thalamocortical activation and suspecnsion of then default state of the brain. Proceedings of the National Academy of Sciences of the United States of America, 102(42), 15236-15240. Doi: 10.1073/pnas.0504935102
  6. Seneviratne, U., Cook, M., & D’Souza, W., (2012). The electroencephalogram of idiopathic generalized epilepsy. Epilepsia, 53(2), 234-248. Doi: 10.1111/j.1528.1167.2011.03344.x.
  7. Sommerville, E., (2012, August, 17). Clinical aspects of Epilepsy [Lecture notes from Neuroscience Fundamentals (Neuro2201) Semester 2, 2012]. Unpublished raw data.
  8. Wang, Z., Zhang, Z., Jiao, Q., Liao, Q., Chen, G., Sun, K., Shen, L., Wang, M., Li, K., Liu, Y., & Lu, G., (2012). Impairments of thalamic nuclei in idiopathic generalized epilepsy revealed by a study combining morphological and functional connectivity MRI. PLoS, 7(7), e39701. Doi:10.1371/journal.pone.0039701
  9. Zhong, Y., Lu, G., Zhang, Z., Jiao, Q., Li, K., & Liu, Y., (2011) Altered regional synchronisation in epileptic patients with generalized tonic-clonic seizures. Epilepsy Research, 97(1-2), 83-81. doi:10.1016/j.epilepsyres.2011.07.007

Scientific Research - Lara
Background Research
Analysis of Media - Anna
Criticism of Media - Dan
Appendix (Dith)