Frontal lobe epilepsy

Frontal lobe epilepsy, or FLE, is a neurological disorder that is characterized by brief, recurring seizures that arise in the frontal lobes of the brain often while the patient is sleeping. It is the second most common type of epilepsy after temporal lobe epilepsy, and is related to the temporal form by the fact that both forms are characterized by the occurrence of partial (focal) seizures. Partial seizures occurring in the frontal lobes can occur in one of two different forms: either simple partial seizures (that do not affect awareness or memory) or complex partial seizures (that affect awareness or memory either before, during or after a seizure). The symptoms and clinical manifestations of frontal lobe epilepsy can differ depending on which specific area of the frontal lobe is affected.

The onset of a seizure may be hard to detect since the frontal lobes contain and regulate many structures and functions about which relatively little is known. Due to the lack of knowledge surrounding the functions associated with the frontal lobes, seizures occurring in these regions of the brain may produce unusual symptoms which can often be misdiagnosed as a psychiatric disorder, non-epileptic seizure or a sleep disorder.

During the onset of a seizure, the patient may exhibit abnormal body posturing, sensorimotor tics, or other abnormalities in motor skills---Cite. In rare cases, uncontrollable laughing or crying may occur during a seizure---Cite. Afflicted persons may or may not be aware that they are behaving in an abnormal manner, depending on the patient and type of seizure. A brief period of confusion known as a postictal state may sometimes follow a seizure occurring in the frontal lobes. However, these postictal states are often times undetectable and generally do not last as long as the periods of confusion following seizures that occur in the temporal lobes.

There are a variety of different causes of frontal lobe epilepsy ranging from genetics to head trauma that result in lesions to the frontal lobes. Although frontal lobe epilepsy is often misdiagnosed, tests such as prolonged EEG monitoring and/or a MRI scan of the frontal lobes can be administered in order to reveal the presence of a tumor or vascular malformation. Medications such as anticonvulsants can typically control the onset of seizures, however, if medications are ineffective the patient may undergo surgery to have focal areas of the frontal lobe removed.

Anatomy of Frontal Lobe Cortex

Due to the difference in brain processing and function as well as various surface anatomy landmarks, the frontal lobes have traditionally been divided into two major areas known as the precentral cortex and prefrontal cortex.

Precentral Cortex

The premotor cortex is an area of the frontal cortex that is located directly anterior to the central sulcus and includes both the primary motor cortex and the supplementary motor area. Inputs that project to both of these areas arise from a variety of locations in the brain that integrate sensory stimuli including the primary motor cortex, the thalamus and corticospinal projections. These two areas along with several other main functional areas control both the preparation of motor movement as well as the execution of movements. These main functional areas are crucial to the development of the motor related symptoms associated with frontal lobe epilepsy focally when seizures are located within these defined areas.. The major functional areas include:

• Primary Motor Cortex
  • Contains large neurons that project axons down to the spinal cord where they synapse onto alpha motor neurons. These neurons are involved in the planning motor movements and the refining of motor movements based off of sensory inputs that are recieved from the cerebellum.

• Supplimentary motor area
  • Area anterior to the primary motor cortex that is involved in planning complex motor movements and coordinating movements along both hands. The main inputs for this area are receieved from the thalamus.

• Frontal eye field
  • The frontal eye field is a posterior part of the middle frontal gyrus and is involved in the control of sccadic, contralateral and conjugate eye movement. This area receives its main inputs from both the occipital cortex and dorsal thalamus.

• Broca's Area
  • Controls the motor movements of both the tongue and larynx that enables speech formation. This area receives direct inputs from the primary motor area as well as wernickes area located in the temporal lobe.

Prefrontal Cortex

The prefrontal cortex, the most anterior region of the brain, is comprised of several key areas that are particularly important for higher mental functions that control various aspects of human personality including anticipation and planning, initiative/judgement, memory and the control of decision making. Damage or lesions to this region of the brain can result major changes in personality including in the loss of impulse control and the formation of aggresive, antisocial behavior. A classic example of how damage can cause a change in behavior is exhibited through story of Phineas Gage. Phineas was a railraod worker who exhibited a severe change in behavior after a railroad spike destroyed his prefontal cortex. There are two main regions of the prefrontal cortex that each control various aspects of behavior and personality:

• Dorsolateral Prefrontal Cortex
  • This area is associated with the impariment of the cognitive abilites to control and regulate behavior and long term memory formation (especially relating to procedural sequence memory) when either brain damage or a lesion is present.

• Orbitofrontal Cortex
  • The orbitofrontal cortex has similar functions as the dorsolateral prefrontal cortex but is thought to be mainly responsible for the ability to make choices and determine right from wrong.

Symptoms

Due to the massive amount of diversity in both the cognitive and motor functions that occur within the frontal lobes, there is an immense variety in the types of symptoms that can arise from seizures caused by epilepsy. In general these symptoms can range anywhere from asymmetric and abnormal body positionsing to repetitive vocal outburts and repetitive jerking movements. The symptoms come in short bursts that usually last less than a minute and have been found to often times occur while a patient is sleeping. Dermatological symptoms of frontal lobe epilepsy used in diagnosis include café-au-lait spots, hypomelanotic macules, and neurofibromas. The symptoms come in short bursts that usually last less than a minute and often occur during sleep. In most cases, a physical or emotional aura precedes the seizure.

Tonic posture and clonic movements are common symptoms among most of the areas of the frontal lobe, therefore the type of seizures associated with frontal lobe epilepsy are commonly called tonic-clonic seizures. A wide range of more specific symptoms arise when different parts of the frontal cortex are affected.

• Supplementary motor area (SMA)
  • The tonic posturing in this area is unilateral or asymmetric between the left and right hemispheres. A somatosensory aura frequently precedes many large motor and vocal symptoms and most often the afflicted person is responsive.
  • Motor symptoms: Facial grimacing and complex automatisms like kicking and pelvic thrusting
  • Vocal symptoms: Laughing, yelling, or speech arrest

• Primary motor cortex
  • The primary motor cortex has jacksonian seizures that spread to adjacent areas of the lobe which often trigger a second round of seizures originating in another cortical area. The seizures are much simpler than those that originate in the SMA and are usually clonic or myoclonic movements with speech arrest. Some dystonic or contralateral adversive posturing may also be present.

• Medial frontal, cingulate gyrus, orbitofrontal, or frontopolar regions
  • Motor symptoms of seizures in this area are accompanied by emotional feelings and viscerosensory symptoms. Motor and vocal agitation are similar to that of the SMA with short repetitive thrashing, pedaling, thrusting, laughing, screaming and/or crying.
  • This is some of what can cause the misdiagnosis of a psychological disorder.

• Dorsolateral cortex
  • This area does not seem to have many motor symptoms beyond tonic posturing or clonic movements. Contralateral or less commonly ipsilateral head turn and eye deviation are commonly associated with this area as well.

• Operculum
  • Many of the symptoms associated with this area involve the head and digestive tract: swallowing, salivation, mastication and possibly gustatory hallucinations. Preceding the seizure the person is fearful and often has an epigastric aura. There is not much physical movement except clonic facial movements. Speech is often arrested.

Causes

The origins of frontal lobe seizures range from tumors to head trauma to genetics. Tumors account for about one third of all frontal lobe epilepsy cases. Low-grade tumors such as gangliogliomas, low-grade gliomas, and epidermoid tumors are most common, but many high-grade tumors were most likely once involved with seizures. Other lesions on the frontal lobe such as hamartomas and nodular heterotopias can cause frontal lobe symptoms as well. Vascular malformation can cause seizures, especially arteriovenous malformations and cavernous angiomas. Head trauma frequently causes damage to the frontal lobe and can cause seizures directly or indirectly through gliosis. Seizures originating directly from head trauma usually occur within months but occasionally can take years to manifest themselves. On occasion encephalitis can cause frontal lobe seizures but it is most often associated with temporal lobe affliction. The main genetic cause of frontal lobe epilepsy is an autosomal dominant disease called Autosomal dominant nocturnal frontal lobe epilepsy, which involves mutations in 2 nicotinic acetylcholine receptor genes. A genetic mutation on chromosome 22 has also been associated with another genetic form of the disorder.

Frequency

Epilepsy is a relatively common disorder, affecting between 0.5-1% of the population. The most common subdivision of epilepsy is symptomatic partial epilepsy, which causes simple partial seizures , and can be further divided into temporal and frontal lobe epilepsy. Although the exact number of cases of frontal lobe epilepsy is not currently known, it is known that FLE is the less common type of partial epilepsy, accounting for 20-30% of operative procedures involving intractable epilepsy. The disorder also has no gender or age bias, affecting males and females of all ages. In a recent study, the mean subject age with frontal lobe epilepsy was 28.5 years old, and the average age of epilepsy onset for left frontal epilepsy was 9.3 years old whereas for right frontal epilepsy it was 11.1 years old.

Treatments

There are several different ways to treat frontal lobe epileptic seizures, however, the most common form of treatment is through the use of anticonvulsant medications that help to prevent seizures from occurring. In some cases, however, when medications are ineffective, a neurologist may choose to operate on the patient in order to remove the focal area of the brain in which the seizures are occurring. Other treatments that can be administered to aid in reducing the occurrence of seizures include the implementation of a specific, regimented diet and/or the implantation of a vagus nerve stimulator.

Medications

Anticonvulsants are the most successful medication in reducing and preventing seizures from reoccurring. The goal of these medications in being able to reduce the reoccurrence of seizures is to be able to limit the amount of rapid and extensive firing of neurons so that a focal region of neurons cannot become over-activated thereby initiating a seizure. Although anticonvulsants are able to reduce the amount of seizures that occur in the brain, no medication has been discovered to date that is able to prevent the development of epilepsy following a head injury. There are a wide range of anticonvulsants that have both different modes of action and different abilities in preventing certain types of seizures. Some of the anticonvulsants that are prescribed to patients today include: Carbamazepine (Tegretol), Phenytoin (Dilantin Kapseals), Gabapentin (Neurontin), Levetiracetam (Keppra), Lamotrigine (Lamictal), Topiramate (Topamax), Tiagabine (Gabitril), Zonisamide (Zonegran) and Pregabalin (Lyrica).

Surgical Treatment

When both the amount and severity of seizures becomes uncontrollable and seizures remain resistant to the various anticonvulsants, a patient most likely will be considered for a frontal lobectomy. This procedure involves the removal of focal regions of the frontal lobes that have been identified as being problematic for the patient. It has been found that around 30% to 50% of patients that undergo a frontal lobectomy will forever be free from seizures that cause a loss of consciousness or cause abnormal movements.

If on the other hand, the seizures occur in an area that is too vital to remove (such as areas that control motor, sensory or language functions), then the surgeon will perform a procedure known as a multiple subpial transection. This procedure involves making a series of cuts that surround the focal region where the seizures have originated. By making cuts surrounding the focal region, the surgeon is able to isolate that specific section of the brain and prevent electrical impulses from being able to travel horizontally to other areas of the brain.

The last surgical procedure that can be done to help aid in preventing the reoccurrence of seizures in the frontal lobes is to implant a stimulator on the vagus nerve. This device is a self-activating device that is inserted directly under the skin and can be controlled directly by the patient. When a patient is feeling the onset of an aura, he/she can activate the stimulator which in turn will provide stimulation to the left vagus nerve (the left vagus nerve is used because the right nerve plays a role in cardiac function). Although little is understood about the exact mechanism for vagal nerve stimulation, it has been proven to be a successful treatment that can often terminate seizures before they begin.

Diet

The use of a regimented diet is an approach that has been found to help control seizures in children with severe, medically-intractable frontal lobe epilepsy. Although the use of dieting to prevent seizures from occurring is a lost treatment that has been replaced by the use of new types of anticonvulsants, it is still recommended to patients to this day. A ketogenic diet is a high-fat, low-carbohydrate based diet that patients are typically asked to follow in conjunction with their anticonvulsant medications.This diet was designed in order to mimic many of the effects that starvation has on the metabolic functioning of the body. By limiting the amount of carbohydrates and increasing the amount of exogenous fats available to the metabolism, the body will create an excess of water-soluble compounds known as ketone bodies. Although the mechanism of action is still unknown, it is believed that these excessive amounts of ketone bodies become the brain's main source of energy and in turn are able to suppress the frequencty of seizure occurance.

Current Research

One of the major concerns for surgeons before they operate on patients that have intractable epilepsis is to not only be able to pinpoint the focal area that is to be removed but to also map out the localized areas surrounding the focal area that are associated with somatosensory and motor functions. Recent research from labs all across the United States has shown that functional magnetic resonance imaging may play a vital role in the near future in being able to clinically identify and map out the regions of the brain surrounding the foci prior to surgery. Functional MRI is a technique in which a map is formed that depicts both the metabolic and physiological consequences of altered electrical activity in the brain. By using this easy to perform diagnostic test, surgeons will be able to map out the sensorimotor, language, visual and memory functional locations in the frontal lobes of the brain prior to the frontal lobectomy. In doing so the doctors will be able to reassure that they will not make cuts on any areas in the brain that will affect vital brain functions.

See also

• Epilepsy
• Temporal Lobe Epilepsy
• Seizures
• Simple partial seizure
• Complex partial seizure
• Frontal lobes
• Anticonvulsant
• Vagus nerve stimulator
• Multiple subpial transection
• Absence seizure
• Psychogenic non-epileptic seizures
• Clonus (e.g. tonic-clonic, or grand mal, seizure)
  • cf. Fasciculation

External links

• Frontal Lobe Epilepsy on Epilepsy.com
• Epilepsy on Neurology Channel