Frontal Lobe Epilepsy
Epilepsy is a seizure disorder where the patient has had more than one unprovoked seizure more than 24 hours apart. There are a variety in ways the disorder can manifest, and this is determined by the region of the brain affected by the seizure and the frequency of the seizures. The region, or regions, of the brain affected reflects the clinical manifestations of the condition. The condition is divided into focal, or partial, seizures and generalized seizures, and this is based on how much of the brain is affected. Partial seizure are seizures that affect one hemisphere or one lobe of the brain. During a partial seizure the patient can either remain conscious or have impaired consciousness, called simple and complex partial seizures, respectively. The state of consciousness is determined by the region of the brain affected. Generalized seizures are seizures that affect both hemispheres. In these cases, the patient loses consciousness for either a brief or long period of time. A partial seizure can spread and develop into a generalized seizure, and these are called secondary generalized seizures. Another catogorization of seizures is by the region the seizure originates from.
A seizure is caused by simultaneous electrical activity of a cluster of neurons. This is abnormal and is what causes the manifestations associated with epilepsy. This causes the action potentials, or electrical signals, in that region to be fired at the same time. Epilepsy is caused either by overactivation of excitatory signals or by hypoactivation of inhibitory signals, both leading to overstimulation of the receptors. Glutamate is the main excitatory neurotransmitter in the brain and NMDA is its most abundant receptor. Rapid or prolonged activation of NMDA by glutamate binding to the receptor can cause the seizure activity. On the other hand, when GABA, which is the main inhibitory neurotransmitter, binds to the GABA receptor, it causes inhibition of action potentials (??). If the GABA receptors are dysfunctioning and cannot bind GABA, the signals cannot be inhibited, which again causes overactivation of the neurons. Mutation of genes encoding for the
Frontal lobe epilepsy (FLE) is the second most common form of epilepsy, and is known for its diverse clinical manifestations. It is a type of partial seizures, and the seizures can either be simple or complex depending on the affected region of the frontal lobe. They are a common cause of secondary generalized seizures and this contributes to the diversity in manifestations of FLE.
There are different causes for this abnormal overactivation in FLE patients, with the most common causes being head trauma, by stroke or mechanical injury, and tumours. A small number of identified FLE patients have a genetic cause. Others is due to abnormal brain tissue, abnormal brain vasculature or previous infection causing permanent scars in the brain (?).
Frontal lobe epilepsy is a group of heterogenous disorders of seizures originating in the frontal lobe. It is the second most common form of focal epilepsy after temporal lobe epilepsy. FLE covers 1-2% of epileptic patients, and epilepsy as a whole affect 1% of the population. The onset of FLE can be anywhere from infancy to the sixth decade, although the majority of cases start in the first or second decade of life. The condition often persists throughout adulthood (why?). There are different causes for the condition, and a few families have been identified to have a genetic cause, however for about 50% of patients suffering from FLE the cause is undetermined.
The frontal lobe is an important functional region for motor, cognition, behaviour, and arousal. During an epileptic episode, the semiology reflects the part of the frontal lobe that is affected.
The variety of clinical manifestations in FLE makes the condition more difficult to diagnose, and in addition, the diagnostic investigations are often not helpful as they give inconclusive results. There are certain characteristics of FLE that occur in the majority of cases, and these characteristics also make it a distinct form of epilepsy. The general manifestations of FLE are that it is most often nocturnal, episodes are stereotypical for the individual, and the duration of the seizure is brief as most last less than 30 seconds. Around 90% of cases have a motor manifestation, which correlated (?) which the frontal lobe’s responsibility for motor functions. Patients commonly recover almost immediately after an episode and they are often conscious during the seizure. The epileptic episodes occur in clusters of an average of 5-6 with or without partial recovery in between the seizures. Other manifestations depend more on which region of the frontal lobe is affected, and the region where the seizure originates from can, to a certain degree, be pinpointed by recognizing these signs and symptoms(?). The frontal lobe seizures are divided into the primary motor cortex, the supplementary motor area, the medial frontal, the dorsolateral cortex, and the operculum.
Seizures originating in the primary motor cortex are usually
Frontal lobe epilepsy is often misdiagnosed as parasomnia and non-epileptic seizure disorders. One of the reasons for this is the diverse manifestations of FLE, and the lack of definitive diagnostic tools.
As mentioned, some individuals have a genetic cause for frontal lobe epilepsy. It is autosomal dominant inheritance, and this form of FLE is therefore called autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). There are two identified mutations in the CHRNA4 and CHRNB2, however, the mutations in these genes are not common as there are other unidentified mutated genes that can cause ADNFLE. In general, FLE caused by a genetic cause is rare. The genes encode for the alfa and beta units of the neuronal nicotinic acetylcholine receptors
For diagnosis of epilepsy in general, brain imaging and EEG can be done. With brain imaging, which uses CT and MRI, the patient can be checked for abnormalities in the brain structure. This can help determining the cause of the frontal lobe epilepsy, and in some cases, like when the condition is caused by a tumour, it can help with surgical intervention. Electroencephalogram is possibly the most important diagnostic tool with video-EEG telemetry being the GOLD standard for diagnosis. EEGs measures the electrical activity in the brain and this can help detect abnormalities, like the hyperactivity occurring during a seizure. Video-EEG telemetry test is a combination of doing an EEG and videoing the patient at the same time. Both ictal and interictal EEG may be taken, however, the results of an EEG can often be misleading as EEGs are prone to artefacts as well as the difficulty detecting the signals as the skull may block the signals. Also, because of the difficulty with the location of the regions of the frontal lobe affected by the seizure, EEG results are often normal. Therefore, diagnostic tools are helpful for confirming or further supporting diagnosis, however, taking a detailed clinical history is the most vital part of a diagnosis.
FLE patients are almost always treated with daily intake of antiepileptic medication. Where appropriate, surgical resection may be performed, however, that is invasive and therefore it is avoided if possible. Another option is vagal nerve stimulation, but like surgery, it is invasive. Recent research also indicates that a ketogenic diet may be beneficial in minimizing seizures, however, the mechanism of this is still not certain.