Focal (Partial) Epilepsy Workup

Laboratory studies, neuroimaging studies, and electroencephalography (EEG) are used in the assessment of focal epilepsies. The following recommendations are derived from the referenced paper. ^[32]

Because the type of seizure (focal vs generalized) and whether it was provoked or unprovoked may not necessarily be clear only from the history, investigate various possible causes for the seizures including structural abnormalities and toxic and metabolic disturbances. One may consider performing the following tests:

• Complete blood count and complete metabolic panel
• A fingerstick glucose
• Urinary drug screen
• Blood alcohol levels
• Urinalysis
• Chest X-ray
• ASM levels (if the patient reports use of these medications)
• Baseline serum prolactin levels and prolactin level 10–20 minutes after a reported event (this has been identified as a possible adjunct in differentiating GTCs from clinical seizures)
• EKG and/or ECHO (especially if syncope is considered in the differential)
• Lumbar puncture (specifically in immunocompromised patients or if there are signs/symptoms of central nervous system infection/encephalitis). One should perform at least basic fluid studies (protein, WBC, glucose) and may consider specific serological testing as guided by the clinical suspicion
• Genetic testing such as genomic hybridization assay, gene panels, and whole exome sequencing (this should be considered in patients with concomitant developmental delay, intellectual impairment, or dysmorphic features)
• ANA, TPO, and CSF/serum neuronal autoantibody panels (this may be considered if an autoimmune encephalitis is suspected as the etiology)

A CT scan of brain without contrast is readily and rapidly available and appropriate in an emergency setting. This is specifically useful to rule out large structural abnormalities, but it may easily miss more subtle findings such as low-grade gliomas, hippocampal sclerosis, and malformations of cortical development.

MRI of the brain, with and without contrast, delineates structural detail and pathology. An epilepsy protocol-specific MRI of the brain should include thin, one to three millimeter slices and coronal fluid-attenuated inversion recovery (FLAIR) sequences to assess for focal cortical dysplasias and hippocampal sclerosis. It is also important for the imaging to be reviewed by an expert neuroradiologist to increase the detection of subtle structural abnormalities.

Electroencephalographic signals provide a real-time assessment of neurophysiologic function; they measure the summation of post-synaptic electrical potentials generated by pyramidal cells in the cerebral cortex. Pyramidal cells are perpendicularly aligned to the cortical surface, producing a vertical dipole detectable by scalp electrodes. However, given the volume conduction effects, at least 6 cm^2 of synchronously firing cortex is needed to generate a signal that is detectable on scalp EEG. It is extremely important that EEG be read by an experienced electroencephalographer, as physiological and extraphysiological artifacts are commonly seen and can render interpretation challenging.

Given that EEG is a real-time assessment of neurologic function, its diagnostic yield is directly related to the amount of time it records. In patients with epilepsy, a standard 30-minute routine EEG detects epileptiform discharges in only 50% of patients; provocation techniques such as sleep deprivation, hyperventilation, and photic stimulation may be used to increase the sensitivity of detecting epileptiform discharges. In contrast, a 24-to-36-hour recording has a greater than 90% likelihood of detecting epileptiform abnormalities. ^[34]

Another factor to consider is how emergently to obtain an EEG recording; generally, if a patient does not return to baseline neurological function within 60 minutes of seizure termination, has waxing-waning level of awareness, or displays acute focal neurologic dysfunction without a structural correlate, emergent inpatient EEG may be justified. In other cases, nonemergent EEG may be pursued, either on an inpatient or outpatient basis.

In inpatient EEG monitoring, patients are admitted to the hospital with slow titration of anti-seizure medications and use of provocation techniques to capture the events in question. This type of admission is usually variously referred to as “long-term monitoring” and requires a designated “epilepsy monitoring unit” with well-trained personnel.

Ambulatory outpatient long-term EEG recordings up to 72 hours in duration are increasingly being utilized in clinical practice to avoid necessitation of inpatient admissions; an important caveat in such a setting is the inability to perform provocation techniques. It should be noted that EEG highly favors detection of temporal lobe involvement in epilepsy and may be less sensitive for detection of focal epilepsies in other lobes. ^[34]

Abnormalities seen in focal epilepsy can be broadly divided into interictal abnormalities and ictal abnormalities Below is a broad summary discussion of these terms, however the updated 2021 ACNS Standardized Critical Care EEG Terminology reference manual should be referenced by electroencephalographers for further specific details. ^[35]

Interictal abnormalities are defined as sporadic epileptiform discharges or rhythmic/periodic patterns that occur “between seizures,” are distinct from background activity, and resemble electrographic patterns recorded in human subjects with epilepsy. As described in the Pathophysiology section, the physiologic basis for interictal abnormalities is the paroxysmal depolarizing shift. It should be noted that approximately 2% of health adults may have interictal discharges; furthermore, the absence of interictal abnormalities does not necessarily exclude the possibility of epilepsy. Specific interictal abnormalities may be divided into the following:

1. Sporadic interictal epileptiform discharges: these are defined as apiculate, diphasic or triphasic waves that are slightly asymmetric with a steeper ascending slope than a descending one. They can be of variable duration, with a “spike” defined as lasting from 20 to 70 milliseconds and a “sharp wave” lasting from 70 to 200 milliseconds. “Polyspikes” is a term that refers to 2 or more spikes in succession lasting less than 0.5 seconds. Immediately afterwards, a slow wave can sometimes be seen and the term “spike-and-wave” and “sharp-and-wave” are then used to describe these morphologies.

2. Rhythmic/periodic patterns: a rhythmic pattern refers to waves that repeat without an interval between consecutive waveforms while a periodic pattern refers to discharges that repeat with clearly regular inter-discharge intervals between them. These patterns should be less than 2.5 Hz in frequency. An added modifier that confers a higher ictal-appearance are whether there are any “plus” features: superimposed fast activity, rhythmic activity, and/or sharp waves.

In describing focal interictal abnormalities on EEG, one should consider whether the pattern in question is lateralized, unilateral independent, bilateral independent, or multifocal. Special attention should also be paid to whether specific lobes are involved; when this is not possible, one can use the term “hemispheric.” There should also be a specification of the prevalence of these interictal abnormalities on the recording.

In contrast, ictal EEG abnormalities refer to electrographic patterns seen during a seizure; an important feature of ictal patterns is evolution in frequency, morphology, or distribution over time. As per consensus 2021 ACNS criteria, electrographic seizures must be either a) epileptiform discharges averaging > 2.5 Hz for 10 seconds; or b) any pattern with definite evolution lasting for > 10 seconds. For focal seizures, status epilepticus is rare but is used to describe seizure that persist for at least 10 minutes.

There is an increasing recognition of “potentially ictal” patterns on EEG with the latest 2021 American Clinical Neurophysiology Society (ACNS) clearly defining two specific terms:

1. Brief potentially ictal rhythmic discharges (BIRDs): these represent electrographic patterns that resemble ictal abnormalities but are less than ten seconds in duration

2. Ictal-interictal continuum (IIC): this term is used to refer to electrographic patterns that do not meet the frequency criteria for ictal abnormalities (< 2.5 Hz) and do not evolve but demonstrate a frequency of > 1Hz and are thought to be potentially ictal in at least some sense.

As part of a pre-surgical workup, further diagnostic imaging modalities may be pursued. Extremely subtle forms of cortical dysplasia may still be undetectable on high-resolution MRI studies and in such cases, further testing with positron emission tomography (PET) or ictal single-photon emission computed tomography (SPECT) is performed.

Functional MRI and diffusion tensor imaging are also used to map eloquent cortex (parts of the brain that are responsible for key language and memory functions) and visualize white matter bundles that should be avoided during surgery.

As part of a pre-surgical workup, there are several further diagnostic tests that may be pursued. For further details regarding pre-surgical work-up, one may refer to the excellent textbook by Stephan Schuele. ^[36]

Magnetoencephalography (MEG)

This is the only noninvasive technology that directly measures neuronal activation while providing high spatial and temporal resolution. Magnetometers measure the magnetic fields generated by cortical electrical activity to localize epileptiform activity at a sublobar level. It is particularly useful to guide surgical EEG lead implantation in MRI-negative cases.

Wada test

This test involves the intracarotid injection of amobarbital, an anesthetic agent, to selectively anesthetize the ipsilateral cerebral hemisphere. This allows for detailed memory and language testing of the remaining “awake” hemisphere.

Neuropsychiatric testing

This should be performed by a qualified neuropsychologist and allows for functional assessment of the brain, confirmatory evidence for seizure laterality, and provides important information regarding potential post-operative neuropsychological deficits.

Surgical EEG monitoring

Invasive intracranial EEG monitoring is particularly needed when noninvasive data are insufficient to delineate the epileptic focus. This may be pursued via either subdural grids, stereotactic guidance (stereo-EEG), or a combination of both depending on the specific case. Grids are more invasive regarding a craniotomy, but they offer spatial contiguity and are particularly useful when the epileptic focus is in proximity to eloquent cortex. Stereo-EEG is less invasive, however is particularly useful when dep structures are implicated as part of the epileptic network such as the insula or mesial temporal lobe.

Electrocorticography and cortical stimulation

This involves applying electrical stimulation to the cortex either intraoperatively or via intracranial electrodes to map eloquent cortex in real time while also allowing for more precise localization of the epileptic focus.