Biology 202, Spring 2005
First Web Papers
On Serendip

Epilepsy is a chronic disorder of the central nervous system, in which nerve cells of the brain produce abnormal pattern of neuronal activity. These imbalanced electrical signals are carried by the nerves, or communicating highways between the brain and the body, to specific peripheral cells and can cause disturbing behaviors, sensation, memory, thought, and emotions. One of the more severe symptoms that are generally used to characterized epilepsy is periodic convulsive seizures (1). Many new treatments for epilepsy over the years are aimed toward treating these recurring seizures and they include medication, surgery, non-drug therapies, and also the ketogenic diet. One treatment, however, that stands out from the rest is called vagus nerve stimulation (VNS). Even though this treatment helps many people with epilepsy, it is still a very controversial treatment since doctors are still puzzled at how the stimulator prevents seizures.

The vagus nerve stimulation is used to treat many different types of epileptic seizures, thus it is important to have an understanding on the types of seizures that are associated with the disorder. Epileptic seizures are usually brought forth by sudden discharges of excess electrical activities within the nervous system and can be classified as generalized or partial seizures. Generalized seizures have more serious effects than partial seizures because the abnormal electrical signals of the nerve cells occur in many diffuse regions of the brain (1). One type of generalized seizure is tonic-clonic seizure, in which muscles alternate between contraction and relaxation, and so some patients may lose bowel or urinary control. Tonic-clonic seizures usually last about 2 to 3 minutes, after which the patients remain unconscious and later awaken to confusion, fatigue and severe headache (1). Absence seizures are also another type of generalized seizures in which the patients suffer for a short cessation (30 seconds) of physical movement and loss of attention that occur around 50 to 100 times a day. Partial seizure, unlike generalized seizure, occurs very often in epileptic patients and is caused by neuron disorders in a particular region of the left or right side of the brain. Simple partial seizure, or Jacksonian epilepsy, is one type of partial seizure in which patients do not lose consciousness but experience jerking movements, confusion, hallucinations, strange thoughts, and extreme reaction toward smell and taste. Complex partial seizure, also a subtype of partial seizure, occurs in the temporal lobe or the region of the brain near the ear. Patients with this type of seizure experience a loss of the ability to make judgments, involuntary behaviors, and also loss of consciousness. Before the actual occurrence of the seizure, patients will experience aura or warning signs, which include feeling of warmth, hallucination, and also repetitive movement (6). There are other seizures that are not related to generalized or partial seizures, and they include atonic seizures, clonic seizures, and myoclonic seizures. The vagus nerve stimulating treatment, however, is more directed toward treating generalized and partial seizures since these types of seizures are often seen in epileptic patients.

The vagus nerve stimulation (VNS) device, or more commonly known as the "pacemaker for the brain", sends regular pulses of electrical energy to the brain by stimulating the vagus nerve. An incision along the outer left side of the chest is made for the implantation of the VNS battery-powered device. In the lower part of the neck, another incision is made in order for the stimulator wire to wind around the vagus nerve. The VNS device is programmed by the neurologist to deliver mild electrical stimulation to the vagus nerve according to the patient's individual needs (1). For instance, some of the typical settings on the device are stimulation amplitude, stimulation frequency, and pulse width. These settings can easily be altered by using a programming wand and a computer. Before a seizure attack, many patients may experience auras or warning signs. The neurologist can easily stop the seizure before it happens by passing a magnet over the device to give it an extra dose of electrical stimulation to the vagus nerve. In order to be considered as a VNS candidate under the American Academy of Neurology, the patients must be over 12 years old, are not suitable for major surgery, and also have partial seizures that cannot be resolved by using medication (6). Some complications that can arise with the VNS procedure include shortness of breath, sore throat, coughing, nausea, and vomiting. These complications can easily be reduced by decreasing the intensity of the stimulation to the vagus nerve by the VNS device.

The idea that the VNS device can reduce seizures seems unfeasible and inconceivable at first glance (before reading the article) because I did not see how stimulating the vagus nerve and the structure itself have anything to do with seizures. The vagus nerve, or pneumogastric nerve, is one of the 12 pairs of cranial nerves and originates in the brain and passes through the neck and thorax into the abdomen. It supplies motor and sensory function to the ear, tongue, larynx, diaphragm, heart, pharynx, stomach, and esophagus (7). All of the important structures that the vagus nerve targets are outside of the brain region and so the vagus nerve did not seem to be related to seizures except for the single fact that the vagus nerve has its origin in the brain. Thus, I wonder if stimulating the vagus nerve will affect other structures that are connected to the vagus nerve? Furthermore, I did not see the mechanism or pathway through which the vagus nerve stimulator works to condition the brain to respond better to interruptions in the functioning of the brain. Does the electrical stimulation from the device destroy the abnormal electrical pattern produced by the neurons, or does it modify the imbalanced electrical signals back to the normal state again?

However, after reading the article "Vagus Nerve Stimulation", I saw that it does provide much solid evidence to support a strong connection between the vagus nerve and seizures (2). For instance, vagal stimulation resulted in changes of the EEG because of the responses from the thalamus and also the ventroposterior complex. The EEG also showed that low frequency stimulation to the vagus nerve can cause synchronization, while high frequency stimulation results in desynchronization (1). In 1988, Penry, Wilder, and Ramsay performed the first VNS device implantation into a human being. There were about 15 people who volunteered for the experiment, and the result showed that seizures were reduced around 50% There has not been a precise model that can describe the action of the VNS to reduce seizures. Researchers, however, discovered that the VNS has the ability to target the medulla, locus cerules, hypothalamus, cingulate gyrus, and amygdala (3). Some of them believe that the VNS reduces seizure in several ways. For instance, VNS causes more GABA and glycine in the brain to be released, which in turn will cause an increase in the threshold for seizure. Action potential will not be created and so there is no current flowing down the axon. Other theories state that the VNS influences the reticular activating system to decrease the cortical epileptiform activity. Another theory claims that the VNS causes changes in the cerebellum, blood flow in the brain, thalamus, and the cortex, which then can activate inhibitory structures in the brain to decrease the seizures activities (2).

Researchers have yet to find out the complete pathway in which stimulating the vagus nerve can cause a decrease in seizures. Thus, vagus nerve stimulating treatment is still under heavier scrutiny from the public and the health industries. Furthermore, there have not been many long-term studies on the side effects of having continuous stimulation to the vagus nerve. I feel, however, that having the vagus nerve subjected to the continuous stimulation might not be a good idea because of the connection between the vagus nerve to other structures. The vagus nerve represents a box in the "boxes inside boxes" model, and so this box is connected to many other boxes like the amygdala .If the vagus nerve is damaged due to the strong electrical stimulant from the VNS devices, other structures around it will also be damaged in the process.

References:
1)Epilepsy, History and Treatments of Epilepsy
2)EMEDICINE on Epilepsy
3)What is Epilepsy
4)The Foundation of Epilepsy
5)VNS Therapy
6)Epilepsy
7) Web Md


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