Overview/Definition:
In a normally functioning brain, cortical neurons communicate via electrical activity in order to control the body and its movements. A seizure is an event occurring in the brain when the electrical activity of an excessive amount of cortical neurons fire simultaneously.

Anatomy of Cerebral Cortex:
The cerebral cortex is the outermost layer of the brain. It is divided into two cortices covering the left and right cerebral hemispheres, which are separated by the medial longitudinal fissure. The cerebral cortex is composed of grey matter. Grey matter consists of neuron cell bodies, dendrites, unmyelinated axons, glial cells, and capillaries.
cortex.jpgThe cerebral cortex is folded in appearance. A fold in the cortex, called a gyrus, gives the cortex a greater surface area without taking up more space within the skull. A groove in the cortex is termed a sulcus. (Photo A).

There are two types of cells in the cerebral cortex. Pyramidal neurons project information to neurons in other, distant areas of the brain. These neurons generally form excitatory synapses on post-synaptic neurons (EPSP’s). Interneurons are neurons that send information to nearby, local neurons. These neurons form inhibitory synapses on pyramidal neurons or other inhibitory neurons (IPSP’s).

The cerebral cortex is composed of six main cortical layers, each made up of different neuronal cell types having different connections with other cortical and subcortical regions. The six layers are as follows:

  • Layer I: the molecular layer; contains glial cells, some neurons, some small pyramidal neurons, horizontally oriented axons, stellate cells. Primarily cortico-cortical afferents.
  • Layer II: the extragranular layer; contains small pyramidal neurons, stellate neurons. Primarily cortico-cortical afferents.
  • Layer III: the extrapyramidal layer; contains small to medium sized pyramidal neurons, some non-pyramidal neurons, vertically oriented axons. Primarily cortico-cortical afferents.
  • Layer IV: the internal granular layer; contains stellate neurons, pyramidal neurons. Primarily thalamocortical afferents; some cortico-cortical afferents.
  • Layer V: the internal pyramidal layer; contains large pyramidal axons. Primarily subcortical axons (to basal ganglia).
  • Layer VI: the polymorphic layer; contains some large pyramidal neurons. Primarily efferent fibers to the thalamus.

The cerebral cortex has connections to many subcortical structures including the thalamus and basal ganglia. The parts of the cortex that receive input from the thalamus have primary sensory areas which are called the primary visual cortex, the primary auditory cortex, and the primary somatosensory cortex. Similarly, there are different motor areas in the cortex which are called the primary motor cortex, the premotor cortex, the posterior parietal cortex and the dorsolateral prefrontal cortex. The basal ganglia is located just beneath the cerebral cortex and is interconnected. There are also various association areas within the cortex which help with perception by integrating information from various receptors and sensory areas and eliciting responses by sending signals to the motor areas1. The cerebral cortex is critical in such functions as memory, attention, perception and awareness, thought, language and consciousness.

Pathophysiology:
In a normally functioning brain, cortical neurons communicate via electrical activity in order to control the body and its movements. A seizure is an event occurring in the brain when an excessive amount of cortical neurons fire simultaneously in an abnormal fashion. When a seizure occurs it can lead to temporary impairment of sensory, motor and cognitive functions.memb potent.png

When looking at normal nerve cells in the brain, the cell has a naturally negative charge because sodium ions, which are positively charged, are being moved out of the cell. When a nerve cell fires, it rapidly becomes positively charged as sodium, potassium, and calcium ions flow into the cell. (Photo B.).

The pathophysiology of seizures can occur due to increased excitation of the nerve cell, decreased inhibition of the nerve cell, or a combination of both. Seizures occur when there is an imbalance between the forces that excite and inhibit neurons, as mentioned before, such that the excitatory forces take over. This electrical signal then extends to surrounding normal brain cells, which start to fire synchronously with the abnormal ones 2,15.

firing ap norm.jpg(Photo C).

This figure depicts the normal firing of a neuron; includes resting potential, an adequate stimulus to induce firing of the neuron, and a hyperpolarized state in which repolarization occurs.







Focal (Partial) Seizure Pathophysiology:
Focal seizures are characterized by showing an interictal epileptiform spike or a sharp wave on EEG’s. This is shown by what is called a paroxysmal depolarization shift (PDS). A PDS is a prolonged calcium-dependent depolarization and results in several sodium-mediated action potentials during the depolarization phase. The PDS is followed by a long period of hyperpolarization. When multiple neurons fire PDSs an interictal spike can be observed on EEG recordings. These spikes can spread to surrounding areas of the cortex and recruit neural tissue to become a seizure3. Focal or partial seizures typically are confined to one brain hemisphere, but they can also spread to the other hemisphere and result in a secondary generalized seizure4.
eeg-spike.jpg(Photo D).pds.png(Photo E).

Generalized Seizure Pathophysiology:
Generalized seizures are characterized by their relation to the thalamocortical circuit, which has oscillation rhythms that alternate between periods of increased excitation and inhibition. The thalamocortical circuit includes the pyramidal neurons mentioned before in the cortex's structure in the neocortex layer, thalamic relay neurons and other
seizure potential.jpgneurons in the nucleus reticularis of the thalamus. Generalized seizures are typically marked by a loss of consciousness and begin in deep brain areas and spread into both brain hemispheres 4.Altered thalamocortical rhythms that are atypical may result in generalized seizures. Typically, the thalamic relay neurons receive ascending inputs from the spinal cord and project to the neocortical pyramidal neurons. The thalamic relay neurons that receive input have oscillations in the resting membrane potential and this increases the probability of other neurons, like the neocortical pyramidal neurons, firing together during depolarization. The oscillations are a result of the transient low-threshold calcium channel. (Photo F).





Types of Seizures:
gen vs partial seiz table.png (Photo G).
Focal seizures: Also known as partial seizures. They occur when there is abnormal electrical activity in the brain in one or more areas on one side of the brain. They can be simple or complex.
  • Simple focal seizure: typically occurs in the occipital lobe and sight may be altered. Muscles are affected the most. Consciousness is not lost.
  • Complex focal seizure: the temporal lobe is the site of activity. Consciousness is usually lost. Sometimes behavior during a seizure can include activity such as running or laughing.

Generalized seizures: This type of seizure involves both sides of the brain rather than just one. There is always loss of consciousness involved. There are various types of generalized seizures.
  • Absence or petit mal seizures: characterized by staring and altered consciousness.
  • Atonic or drop attacks: sudden loss of muscle tone and characterized by unresponsiveness.
  • Generalized tonic-clonic or Grand mal seizures: five phases occur – flexion of the body, arms, and legs, extension, tremor, clonic period (contraction and relaxation of muscles), and postictal period (sleepiness, fatigue, body aches)
  • Myoclonic: jerking movements; occurs in quick successions.
  • Infantile spasms: very rare, occurring in infants. Characterized by brief periods of movement of the neck, trunk, and legs.
  • Febrile: common in children and associated with fevers. They can be simple and not have lasting effects, or they can be complex and last for over fifteen minutes with long-term neurological effects5.

Symptoms:
The symptoms of a seizure can vary from subtle signs to quite alarming signals. During a seizure, a person may experience or exhibit the following:
  • Staring
  • Jerking movements
  • Stiffening of the body
  • Loss of consciousness
  • Falling suddenly
  • Trouble or cessation of breathing
  • Unresponsiveness
  • Confusion
  • Rapid eye blinking
  • Irritability or sleepiness.5

Causes:
At birth, congenital problems, infection, fever, or chemical imbalances can cause seizures. Throughout life, alcohol and drugs, head trauma, infections, congenital conditions, genetic factors, progressive brain diseases, Alzheimer’s disease, and strokes can cause seizures. Additionally, certain medications, drug withdrawals, brain tumors or other neurological problems can result in seizures5.


Specific Examples of Seizures Associated with Cortices:

Epilepsy:
Epilepsy is a neurological disorder in which repeated seizures are experienced by an individual. A seizure alone does not mean someone has epilepsy and typically one must experience two or more unprovoked seizures6.


Jacksonian seizure: Jacksonian seizures fall within the realm of epilepsy, and occur when a simple partial seizure arising in only part of the brain, generally the frontal lobe, spreads from a distal portion of a limb to the face or other muscle groups on the ipsilateral side7.
jacksonian seiz.gif(Photo H).
The “march” is a key characteristic to a Jacksonian seizure. The seizure begins as a twitch in a finger, toe, or mouth muscles and then marches to initiate abnormal twitching or sensations in the entire hand, foot or face8. They arise in the primary motor cortex as a result of abnormal electrical activity. Since they arise in the PMC, this type of seizure affects the corresponding muscles with the motor homunculus as a result of the somatotopic mapping that exists9. This is why typically a Jacksonian seizure begins by affecting the fingers.


Temporal lobe epilepsy: This is the most common type of epilepsy. This is a form of focal epilepsy and seizures originate in one or both temporal lobes of the brain.
There are two main types of temporal lobe epilepsy:
  • Mesial temporal lobe epilepsy (MTLE) which originates in the hippocampus, parahippocampal gyrus and amygdale (all within the temporal lobe)
  • Lateral temporal lobe epilepsy (LTLE) which originates in the neocortex (on the surface of the temporal lobe). (Photo I).
lobes.gif
The partial seizures occurring in the temporal lobe seizures can be simple (not affecting awareness or memory) or complex (impairing awareness and/or memory from before, during, or after the seizure)10. These seizures spread to all areas of the temporal lobes and often even infringe on other lobes of the brain, like the frontal, parietal and occipital lobes on either the same or opposite side.

A unique characteristic of temporal lobe seizures is the presence of auras or warnings that someone may experience just prior to the onset of a seizure. Such auras or warnings could include: resurfacing memories, feelings of familiarity or déjà vu, feelings of foreignness or strangeness, hallucinations of voices or smells11. In about 60% of people with temporal lobe epilepsy, seizures spread in a process termed secondary generalization and result in a convulsive or grand mal seizure11. Since these seizures originate deep within the temporal lobe, where the limbic system arises, emotions and memory are often affected.

frontal seizure.jpg(Photo J).

Frontal lobe epilepsy: These partial seizures originate in the frontal lobe of the brain and are the second most common type of epilepsy12. They can be simple or complex. They often occur during sleep and have very short durations (1 minute). These seizures can cause muscle weakness depending on where in the frontal lobe they originate. Symptoms range from bike pedaling motions with the legs and pelvic thrusting, to screaming12.


Conclusion:
Seizures can vary in terms of severity of symptoms and also the causes underlying the manifestation of their occurrence. There are some methods of treatment to cure or manage certain seizures and epilepsies, including different drugs and even surgical procedures within the lobe where seizures are occurring13,14. Diagnosing seizures and different forms of epilepsy can be a tricky process undertaken by doctors and neurologists, as seizures are quite complex and can sometimes manifest to look like other conditions.


For further reading, see the websites listed below:
http://www.ieaecell.org/epilepsy-01.html
http://www.epilepsyfoundation.org.





Glossary:
  • Cerebral cortex: the outermost layer of the brain, composed of six layers.
  • Focal (Partial) seizure: confined to one hemisphere or lobe of the brain. Can be simple or complex.
  • Secondary generalized seizure: when a focal seizure spreads to the other hemisphere.
  • Generalized seizure: spread to both hemispheres of the brain and induce loss of consciousness.
  • Epilepsy: a neurological disorder in which repeated seizures are experienced by an individual


Quiz:
  1. The outermost layer of the brain is the:
    a. somatosensory cortex
    b. cerebral cortex
    c. primary motor cortex
  2. This anatomical phenomenon in the cortex gives the cortex a greater surface area without taking up more space within the skull.
    a. gyrus
    b. groove
    c. sulcus
  3. The cerebral cortex is composed of how many main layers?
    a. 5
    b. 8
    c. 6
  4. The cerebral cortex is critical in various functions such as
    a. memory and attention
    b. perception and awareness
    c. thought, language and consciousness.
    d. all of the above
  5. Normal nerve cells in the brain have a naturally positive charge at rest: True / False
  6. Head trauma, fevers, and brain diseases can all causes seizures to occur: True / False
  7. Epilepsy is a neurological disorder in which a single episode of a seizure is experienced by an individual: True / False
  8. The “march” is a key characteristic to a Jacksonian seizure: True / False
  9. Frontal lobe epilepsy is the most common type of epilepsy: True / False
  10. The pathophysiology of seizures can occur due to increased excitation of the nerve cell, decreased inhibition of the nerve cell, or a combination of both. True / False
  11. Why do seizures occur? Explain the process that occurs in the brain with a seizure.
  12. What is the biggest difference between a Focal seizure and a Generalized seizure?
  13. What is epilepsy? Give one example of a seizure that occurs in the cortices.


Resources:
    1. Bromfield, E. (2006) NCBI: An Introduction to Epilepsy [Online]. American Epilepsy Society. (http://www.ncbi.nlm.nih.gov/books/NBK2510/) [4 Nov. 2013].
    2. Henthorn, T (2013). Wisegeek: What is the Pathophysiology of Seizures? [Online]. Conjecture Corporation. (http://www.wisegeek.com/what-is-the-pathophysiology-of-seizures.htm) [4 Nov. 2013].
    3. Ko,D. (2013). Medscape: Epilepsy and Seizures [Online]. WebMD LLC. (http://emedicine.medscape.com/article/1184846-overview#aw2aab6b2b2). [4 Nov. 2013].
    4. Bhagwati, S. (2013). E-Cell: Epilepsy; Manifestations of Seizures [Online]. Indian Epilepsy Association. (http://www.ieaecell.org/epilepsy-02.html). [20 Nov. 2013].
    5. Miller School of Medicine Health Library (2013). UHealth: Epilepsy and Seizures [Online]. University of Miami Health System. (http://uhealthsystem.com/health-library/neuro/disorder/epilepsy).[20 Nov. 2013].
    6. Mayo Clinic Staff. (2013). Mayo Clinic: Epilepsy; Definition [Online]. Mayo Foundation for Medical Education and Research. (http://www.mayoclinic.com/health/epilepsy/DS00342). [20 Nov. 2013].
    7. Jacksonian Seizure. (2013) [Online]. Wikipedia. (http://en.wikipedia.org/wiki/Jacksonian_seizure). [25 Nov. 2013].
    8. Benbadis, S. (2013). Epilepsy: Do you Know What a Jacksonian March is? [Online]. Epilepsy.com/Professionals. (http://professionals.epilepsy.com/page/newsletter_061913_jacksonian_march.html). [25 Nov. 2013].
    9. Primary Motor Cortex. (2013) [Online]. Wikipedia. (http://en.wikipedia.org/wiki/Primary_motor_cortex). [25 Nov. 2013].
    10. Mayo Clinic Staff. (2013). Mayo Clinic: Temporal Lobe Seizures [Online]. Mayo Foundation for Medical Education and Research. (http://www.mayoclinic.com/health/frontal-lobe-seizures/DS00810). [25 Nov. 2013].
    11. Holmes, G. (2006). Epilepsy.com: Temporal Lobe Epilepsy [Online]. Epilepsy.com (http://www.epilepsy.com/epilepsy/epilepsy_temporallobe). [25 Nov. 2013].
    12. Mayo Clinic Staff. (2013). Mayo Clinic: Frontal Lobe Seizures [Online]. Mayo Foundation for Medical Education and Research. (http://www.mayoclinic.com/health/frontal-lobe-seizures/DS00810 [25 Nov. 2013].
    13. Kumar, Atul. "Preoperative estimation of seizure control after resective surgery for the treatment of epilepsy." Seizure. 22.10 (20130): 818-826. Web. 1 Dec 2013.
    14. Yu Tao. "Surgical treatment of hypermotor seizures originating from the temporal lobe." Seizire. 22.10 (2013): 862-866. Web. 1 Dec 2013.
    15. Traub, RD. "Cellular mechanism of neuronal synchronization in epilepsy." Science. 215.4547 (1982): 745-747. Web. 1 Dec 2013.

Images:
A. The Outside of the Brain. Digital image. Count Your Culture. N.p., 2013. Web. 26 Nov. 2013. <http://countyourculture.com/tag/cerebral-cortex/>
B. Chong, D. Membrane Potentials. Digital image. ChemWiki. UC Davis, 2013. Web. 26 Nov. 2013
<http://chemwiki.ucdavis.edu/Analytical_Chemistry/Electrochemistry/Case_Studies/Membrane_Potentials>
C. How Neurons Communicate. Digital image. Connexions. Open Stax College, 2013. Web. 26 Nov. 2013.
<http://cnx.org/content/m44748/latest/?collection=col11448/latest>.
D. Focal Spike on EEG in Epilepsy. Digital image. Neurology Update. Barnabas Health, 2013. Web. 26 Nov. 2013.
<http://cnx.org/content/m44748/latest/?collection=col11448/latest>
E. Zahr, M. Pathophysiology of Epilepsy. Digital image. N.p., 2013. Web. 26 Nov. 2013. <http://dc442.4shared.com/doc/_daa9SZD/preview.html>
F. Epilepsy Manifestations of Seizures. Digital image. ECell. Indian Epilepsy Association, 2013. Web. 26 Nov. 2013. <http://www.ieaecell.org/epilepsy-03.html>
G. Carstensen, A. Primary Motor Cortex. Digital image. N.p., 2003. Web. 26 Nov. 2013. <http://www.ieaecell.org/epilepsy-03.html>.
H. Seizure. Digital image. N.p., 2013. Web. 26 Nov. 2013. <http://meddic.jp/seizure>.
I. Temporal Lobe Epilepsy. Digital image. Epilepsy Foundation. Epilepsy Foundation, 2013. Web. 26 Nov. 2013.
<http://www.epilepsyfoundation.org/aboutepilepsy/syndromes/temporallobeepilepsy.cfm>.
J. Dávila-García, M. Epilepsy. Digital image. Sistema Nervoso. Howard University, 2005. Web. 26 Nov. 2013.
<http://sistemanervoso.com/pagina.php?secao=7&materia_id=587&materiaver=1>.


Answers:
1) b, 2) a, 3) c, 4) d, 5) False, 6) True, 7) False, 8) True, 9) False, 10) True.
11) Seizures can occur due to increased excitation of the nerve cell, decreased inhibition of the nerve cell, or a combination of both. Seizures occur when there is an imbalance between the forces that excite and inhibit neurons, such that the excitatory forces take over. This electrical signal then extends to surrounding normal brain cells, which start to fire synchronously with the abnormal ones.
12) Focal or partial seizures typically are confined to one brain hemisphere while Generalized seizure involve both sides of the brain.
13) Epilepsy is a neurological disorder in which repeated seizures are experienced by an individual. A seizure alone does not mean someone has epilepsy and typically one must experience two or more unprovoked seizures. Jacksonian/Temporal Lobe/Frontal Lobe seizures all occur in the cortices.