Frontal Lobe Epilepsy Workup

Blood testing

Blood tests should be performed to rule out a metabolic cause of new-onset seizures, eg, hypoglycemia or hypomagnesemia. Once the diagnosis of epilepsy is established, blood testing remains important in the management of patients who are taking anticonvulsants. Blood monitoring should be guided by the likely complications of a given anticonvulsant and, more importantly, by patient risk factors and symptoms. Blood tests include the following:

• Complete blood count (CBC) - Monitor for neutropenia and thrombocytopenia

• Basic metabolic panel - Monitor for hyponatremia

• Liver function tests

• Anti-seizure medication levels - Most anti-seizure medications have a typical therapeutic window, although these levels should be used only as a guide. For new anticonvulsants, the therapeutic range is not as well established and thus levels are less frequently checked

• Genetic testing - If there is a strong family history of epilepsy

With regard to the third item above, most anticonvulsants have a typical therapeutic window, although these levels should be used only as a guide. levels are less frequently monitored for the newer anticonvulsant agents.

Magnetic resonance imaging

The imaging modality of choice in patients with frontal lobe seizures is MRI. Recent advances in MRI have improved the identification of underlying lesions, which are reported to be present in up to 50% of patients with frontal lobe epilepsy.

Optimally, MRI should be obtained with high resolution, 1 mm thick slices, and multiple sequences. If EEG or other testing indicates a potential epileptogenic zone, thin slices through the area of interest should be requested. A field strength of 3 Tesla (3T) can further increase the identification of lesions. ^[2]

Positron emission tomography scanning

PET scanning is being increasingly used in the presurgical evaluation of patients with extratemporal epilepsy.

Interictal hypometabolism, reflective of focal dysfunction, may be seen in areas that were normal on MRI, although this finding is better established for temporal than for frontal lobe epilepsy. The role of tracer-imaging functions other than glucose metabolism, such as benzodiazepine receptors, still is being defined.

Decreased thalamic metabolism ipsilateral to the seizure focus may be seen in nonlesional frontal lobe epilepsy, particularly in association with a long duration of intractability.

If the patient has very frequent seizures, and particularly if he/she does not recognize not all seizures, then consider performing an ambulatory EEG for the 48–72 hours leading up to the PET scan to establish whether the study was truly interictal.

Single-photon emission computed tomography

Ictal single-photon emission computed tomography (SPECT) scans may be obtained during prolonged video-EEG monitoring.

Hyperperfusion seen on ictal SPECT scanning is suggestive of an area of seizure onset. The sensitivity of ictal SPECT scan hyperperfusion is reported to be higher in frontal lobe epilepsy than in temporal lobe epilepsy.

As seizures in patients with frontal lobe epilepsy are often brief and may generalize rapidly, obtaining an ictal SPECT scan is difficult.

Magnetic resonance spectroscopy

Magnetic resonance spectroscopy (MRS), while still mainly an experimental testing modality, is being increasingly used in the presurgical evaluation of intractable epilepsy.

MRS may demonstrate decreased NA/Cr ratios in the frontal epileptogenic zone, consistent with abnormalities of energy metabolism. However, there are no published studies examining this imaging modality specifically for frontal lobe epilepsy.

Electroencephalography

All patients with frontal lobe epilepsy should undergo EEG evaluation. Patients with intractable epilepsy, or in whom the diagnosis is doubtful, should undergo prolonged video-EEG monitoring. If the events are primarily or exclusively nocturnal, polysomnography should be considered, with extended EEG montages if available. Electroencephalography is discussed further in the subsections below.

Magnetoencephalography

Magnetoencephalography (MEG) is a functional neuroimaging modality that uses the brain’s magnetic fields to map brain activity. One study found that source localization using MEG provided important localization information and impacted surgical outcome in patients with frontal lobe epilepsy. ^[13]

Histologic findings

Tissue from surgical resections for intractable frontal lobe epilepsy may demonstrate evidence of a developmental lesion, tumor, gliosis, or vascular malformation. However, the histologic findings may be confounded by post-surgical changes.

Interictal EEG

There are no pathognomonic EEG findings for frontal lobe epilepsy. In fact, interictal EEGs may be normal. Spikes or sharp waves may be absent; may appear maximal unilaterally (frontal or frontopolar), bilaterally, or in the midline (vertex); or may appear generalized due to secondary bilateral synchrony. ^[14] Multifocal spikes may be associated with a higher tendency for a history of bilateral evolution to tonic-clonic seizures. ^[15]

Background rhythm abnormalities, with or without focal slowing, may be present and usually depend on the presence of a structural lesion.

Ictal EEG

Ictal onset often is seen poorly from the scalp and is highly variable in appearance. EEGs can also be affected by muscle artifact, which may obscure the findings. Closely spaced frontal electrodes can enhance localization in ictal EEGs.

Lack of ictal discharge in the temporal lobes may suggest a frontal onset.

Video analysis of seizure semiology is crucial and may suggest frontal lobe epilepsy when the EEG is unrevealing. Fencing posturing and lack of postictal confusion are highly suggestive of frontal lobe seizures. ^[4]

Clinical semiology can provide lateralization information, with many unilateral movements or postures predicting a contralateral seizure onset. ^[16]

Mesial frontal lobe seizures may be characterized by generalized epileptiform discharges at onset , which are maximal at vertex. Dorsolateral frontal lobe seizures are frequently characterized by focal rhythmic activity, and non-localizable seizures may manifest as diffuse attenuation of the background activity and non-localized rhythmic theta or delta at onset. ^[14]  

Postictal EEG

Postictal slowing also can be confirmatory, and at times, localizing or lateralizing.

Go to EEG Video Monitoring for complete information on this topic.

High-density EEG and electrical source imaging

High-density (HD) EEG and electrical source imaging (ESI) are additional neurophysiologic modalities that can aid in localization, particularly for patients undergoing surgical work-up. HD EEG refers to using 64 or more electrodes, which can improve the accuracy of localization compared to standard EEG arrays. ESI uses mathematical algorithms to plot the interictal epileptiform discharges or initial ictal discharge on MRI images. Using the patient’s MRI, as opposed to an MRI template, leads to more accurate localization. Of note, these modalities are only useful if the patient’s interictal and/or initial ictal discharges are well-visualized on scalp EEG.

Patients with suspected frontal lobe epilepsy frequently require invasive EEG monitoring. Intracranial EEG is used for localizing the epileptogenic region and for functional mapping prior to resection when seizures arise close to eloquent cortex (eg, motor or language functional areas). Electrode coverage of frontal and temporal (and/or parietal) lobes may be needed.

Stereotactically placed depth electrodes have the greatest accuracy if the area of interest is well defined, but records from a small anatomic area.

Subdural strips and grids sample more broadly, and can be used to perform cortical mapping, but they have higher infection risk and less anatomic specificity. 

Interictal high-frequency oscillations (HFO) have localizing value in frontal lobe epilepsy, with their pre-resection presence predicting a postoperative seizure-free outcome. ^{[14, 17]}

Ictal onset most often appears as a low-voltage, high-frequency discharge (ie, buzz), although rhythmic activity at alpha, theta, or delta frequencies may be seen. Because of rapid bilateral synchrony, discharge on scalp recording may appear bilateral.