Epilepsy and How to Find Your Way in the Nervous System

Epilepsy

Epilepsy is a common neurological disorder that consists of recurrent disturbances of electrical activity in the brain involving large ensembles of neurons.These cells fire synchronously (at the same time), producing distinct electroencephalograms (EEGs) that vary with the type of seizure.The EEG reflects the summation of electrical activity of tens of thousands of neurons in the cerebral cortex beneath the electrodes pasted to the outside of the skull. EEG recordings show that in healthy individuals, neurons fire at different times, so the wave looks rapid and choppy and low in amplitude. During a seizure, clusters of neurons fire at the same time, so the record appears with slow and rhythmic frequency but high amplitude. Although there are many events that can initiate a seizure, once the abnormal bursts of action potentials begin it spreads from the origin (called the focus) to surrounding neurons and via synaptic pathways that are connected to the original site. Generalized seizures appear to start in multiple brain areas all at once and involve large areas of the cerebral cortex.The physical signs of the seizure depend upon which brain areas are involved in the uncontrolled electrical activity. Although none of the individual neurons are abnormal, the regulation of their firing is atypical.

An additional characteristic of seizures is that they spontaneously end in 15 seconds to 5 minutes because neurons become depleted of ATP. Vast amounts of energy are required to maintain the high rate of firing, because the Na+-K+ pump utilizes ATP to restore the balance of ions that is needed to generate further action potentials. However, some abnormalities in the EEG are still apparent between seizures, and the subtle differences are useful in diagnosing the particular type of seizure.

While the precipitating factor for the onset of epilepsy is not known in some cases and is apparently developmental, in other cases the origin of the recurrent seizures is linked to a brain injury that makes neuronal circuits hyperexcitable, leading to spontaneous recurrent seizures.The types of brain injury are varied and include intrauterine and neonatal damage, stroke, damage caused by environmental toxins or drug use, brain trauma such as occurs during an auto accident, and so forth.

Although diagnosis depends on evaluating the EEG records, intracellular recording with microelectrodes is needed to examine the cell function of individual neurons within the seizure focus.The normal action potential of a neuron  involves the gradual change in membrane potential to the threshold, rapid depolarization (the spike) caused by the opening of voltage-gated Na+ channels, rapid repolarization (a return toward resting potential during the absolute refractory period), and characteristic hyperpolarization. Neurons within the seizure focus appear to differ in several respects. First, the depolarization is higher voltage and continues for a longer period of time, during which mini-spikes are evident. The occurrence of the mini-spikes is the likely explanation for the recruitment of adjacent neurons during the seizure.Second, the hyperpolarization (relative refractory period) that occurs is both greater in magnitude and also extends for a longer period of time.

Among the pharmacological treatments for seizures is the drug phenytoin (Dilantin). Phenytoin, which rep-resents one strategy for seizure control, acts by changing the normal cycling of the voltage-gated Na+ channels that are responsible for the massive depolarization (spike) of the action potential. Phenytoin binds to the channel during the absolute refractory period, when it is closed and cannot be opened, holding it in that state. By preventing the minispikes, the drug prevents the spread of electrical activity to adjacent cells.

A second strategy is to enhance neurochemical inhibition. Increasing inhibition may keep cells in the focus from reaching the threshold for firing or prevent the recruitment of associated neurons. Drugs that increase the inhibitory effects of the neurotrans-mitter GABA (a-aminobutyric acid) are discussed in a future post.

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Finding Your Way in the Nervous System

In order to discuss anatomical relationships systematic method to describe location in three dimensions is needed.The directions are based on the neuraxis, an imaginary line beginning at the base of the spinal cord and ending at the front of the brain. For most animals the neuraxis is a straight line; however, because humans walk upright, the neuraxis bends, changing the relationship of the brain to the spinal cord. For this reason, both the top of the head and the back of the body are called dorsal, while ventral refers to the underside of the brain and the front surface of the body.To avoid confusion, sometimes the top of the human brain is described as superior and the bottom, inferior. In addition, the head end of the nervous system is anterior or rostral and the tail end is posterior or caudal. Finally, medial means toward the center or midline of the body and lateral means toward the side. We can describe the location of any brain area using these three pairs of dimensional descriptors.

Much of our knowledge about the structure of the nervous system comes from examining two-dimensional slices.The orientation of the slice (or section) is typically in any one of three different planes:

• Horizontal sections are slices parallel to the horizon.

• Sagittal sections are cut on the plane that bisects the nervous systern into right and left halves.The midsagittal section is the slice that divides the brain into left and right symmetrical pieces.

• Coronal (or frontal) sections are cut parallel to the face.

Identifying specific structures in these different views takes a good deal of experience. However, computer- assisted evaluation allows us to visualize the brain of a living human in far greater detail than was previously possible. MRI and computerized tomography not only provide detailed anatomical images of brain slices but also reconstruct threedimensional images of the brain using mathematical techniques. PET and MRI provide a view of the functioning brain by mapping blood flow or glucose utilization in various disease states,following drug administration, or during other experimental manipulations.

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