EEG, Epilepsy and Status Epilepticus
Basic Principles of Analog & Digital EEG Recording
Since the first human EEG recordings by Hans Berger, the EEG machine has gradually evolved from its humble beginnings. From Berger's string galvanometer to single, then few, then multiple-channel analog machines recording on reams of contiguous paper to the current sophisticated multi-channel extremely portable computer-based digital EEG machines loaded with accompanying analyses and brain mapping software. Accessibility of data acquisition and review has also undergone tremendous improvements from the once stationary, bulky set-up to ambulatory EEG acquisition devices and accessibility of data review via local area networks and even through wireless media formats. Without a basic understanding of the principles of analog & digital EEG recording though, the would-be EEG reader risks being held ransom by advancing technology and being unable to ensure safe use of the machine or identifying the various idiosyncratic artifacts that may often arise with the use of these machines.
Minute electrical brain activity first needs to be picked up by the use of electrodes placed securely on the scalp. This is then transmitted via electrical wires to the electrode box or jackbox. A selector allows each electrode input to be viewed in relation to another in an electrode array or montage. Brain activity is then passed through a series of filters (high/low frequency) set to optimize assessment of physiologic frequencies and then amplified. The latter amplified signal is then recorded on a pen-writer unit (analog) or digitized via an analog-digital converter and presented on a computer monitor.
A montage is a combination of electrodes examined at a particular time point. Montages help to direct the EEG reader's attention to activity recorded by the electrodes, aid in the localization of such activity and compare the magnitude of such activity with other regions of the brain. Some examples of montages include:
Referential montage - electrodes examined wrt to a particular reference electrode.
Longitudinal bipolar ("double banana") montage - links a temporal and a parasagittal chain of electrodes in a front to back manner.
Transverse bipolar montage - links electrodes across the head eg from left to right.
Digital EEG is recorded referentially and has the advantage over paper EEG of re-montaging after EEG acquisition.
Amplifiers serve to increase the amplitude of the signals passed into them by a factor known as the "gain factor". Sensitivity is the term used to denote the amount of electrical potential corresponding to a unit deflection on paper/screen (eg 10uV/mm). Amplifier gain is measured in decibels (dB). A dB is defined as 20 times the log of the ratio between the output and input signals. Amplifiers are equipped to receive inputs within a certain voltage range called a dynamic range. In order for amplifiers to accurately represent input signals at their outputs, they must maintain amplitude linearity (eg if input signal doubles, output signal must also double), phase linearity (all frequencies amplified must be shifted by a constant time) and have an adequate frequency bandwidth to apply an equal gain factor to all their input frequencies. Differential amplifiers have two different input terminals and amplify only the differences between the inputs at these two terminals; signals which are common to both inputs are cancelled out (common mode rejection).
Filters serve a transfer function between the input and output signal wrt frequency; ie any gain (or loss) of the input signal depends on the frequency of that signal. ,Filters are usually employed to reduce external interference, limit the frequency range under study, prevent aliasing during analog to digital conversion and remove baseline offset. Low-pass filters (High frequency filters) allow frequencies from 0 or DC up to the cutoff frequency to pass but attenuates all frequencies at or above the cutoff frequency.
High-pass filters (Low frequency filters) allow frequencies above the cutoff frequency to pass while attenuating those at or below the cutoff frequency.
Band-stop filter ( "Notch" filter) attenuates all frequencies within a defined "stop-band" (usually narrow) while allowing all other frequencies to pass.
Analog to Digital Converter (ADC)
This is the "engine" of the digital EEG. It is a circuit board that measures input voltages to its channels per unit time (sampling rate). The higher the sampling rate, the better the reproduction of the input signal. Low sampling rates can lead to a phenomenon called "aliasing".
Aliasing occurs when the sampling rate is too slow to resolve the high frequency components of an input signal; the resultant output signal becomes instead much lower in frequency compared to the true input signal frequency. Nyquist's Theorem states that in order to reliably digitize a signal of given frequency, the signal must be sampled at a rate of more than two times that frequency.
Precision of the ADC is also dependant on its vertical resolution, a measure of how finely the input voltage can be subdivided when measured. The greater the number of subdivisions available for voltage resolution, the smoother the output signal would appear with each small increment or decrement of input voltage.
Devices on ADCs allow signals from all input channels to be sampled simultaneously or sequentially (and held so as to align data points in time).
Data Presentation & Storage
Analog EEG machines record data via pen-writer units on scrolling paper. The speed of the latter can be controlled. In order to view electrode recordings in different montages or at different paper speeds, the technician has to select the corresponding electrode arrays by changing the input selector switches & also the roller speed in real time recording. Careful management of the pen-writer unit is also important to prevent pen-blocking and ink smudges.
Digital EEG machines record data referentially and present digitized data on computer monitors. Re-montaging and viewing channel recordings at different speeds can be done after data acquisition. Poor monitor resolution may hamper the effective presentation of precisely sampled EEG data whilst a small screen size may lead to cramping of EEG channels and make it strenuous for EEG reading..
Data storage and portability with digital EEG is far superior to that of the bulky, space consuming paper of analog EEG.
While digital EEG has revolutionized how EEG is recorded, analyzed and stored, it is pertinent still to remember the basic principles in EEG recording and the special pitfalls that digitization brings with it.
Epilepsy and its mimics
Epilepsy is diagnosed when a person suffers two or more unprovoked epileptic seizures. Often, however, epileptic seizures may arise from acute provoking factors which may be recurrent (eg hypoglycaemia) and do not constitute a diagnosis of epilepsy. Seizures may also be mimicked by a host of movement disorders with or without accompanying alteration of awareness while the latter itself (with or without other subtle clinical signs) could represent epileptic seizures. It is thus pertinent to be aware of the clinical caveats and pitfalls in the clinical diagnosis of epileptic seizures and their mimics.
A careful history from the patient and eye-witnesses is critical to the diagnosis of epileptic seizures. The history surrounding the episode(s) in question should begin with the presence/absence of any preceding aura. Clear epileptic auras imply a focal seizure onset. It should also determine the duration of each phase of the episode (eg duration of aura or spread of aura to secondary generalization) and seek to reconstruct the clinical details of the episode proper. It may be useful to ask eye-witnesses to re-enact the witnessed episode. Clinical information like vocalization, eye opening, foaming at the mouth, urinary/bowel incontinence, limb posture and/or manner of jerking/stiffening are all useful in determining the nature and progression of the described episode.
Several other neurological and medical conditions may mimic epileptic auras or the motor manifestations of epileptic seizures. These include migrainous auras, transient ischaemic attacks, hyperventilation attacks, syncopal attacks and the various movement disorders.
The clinician then needs to synthesize the presented clinical information and compare it with his knowledge of neuroanatomy, neurophysiology and seizure semeiology to determine if a reported episode represents an epileptic seizure. Knowledge of typical epileptic auras, semeiology of seizures arising from different regions of the brain and progressing in a neuroanatomically sensible manner aid in dissecting the clinical features of a presented episode.
Though the presence of an ictal pattern on EEG during an episode helps to confirm a diagnosis of epileptic seizure, this is often fortuitous; the absence of a clear ictal EEG pattern (obscured by muscle or seizure arising from areas of the brain "hidden" from scalp EEG electrodes) during an episode on the other hand does not conclusively exclude the diagnosis of epileptic seizure. The diagnosis of epilepsy remains a clinical one.
Psychogenic seizures may mislead the most experienced of clinicians and lead to a delay in diagnosis, unnecessary medications, unwarranted side-effects and occasionally contribute to an entrenched sickness behaviour.
To the untrained eye, the clinical features of psychogenic seizures may appear very similar to epileptic seizures. Closer scrutiny will often reveal clinical clues useful in telling the two apart. The latter include:
- Retention of volition in the midst of a generalized "seizure"
- Clinical features which contradict conventional anatomical spread of neurophysiological activity
- Long episode duration (occasional with cycles of repetition)
- Suggestibility (onset and offset) and distractability
Management or Status Epilepticus
The management of status epilepticus(SE) remains a challenging task for any epileptologist, neuro-intensivist or physician looking after patients with epilepsy or practicing in an intensive care setting.
Ideal management begins with the prompt diagnosis of the condition followed by equally rapid measures to terminate the patient's seizures with appropriate medications at adequate doses and to treat any accompanying systemic compromise. Subsequent management seeks to minimize breakthrough seizures and to detect and treat these should they occur. There is still much to be done to improve each step of the process described.
Definitions & Diagnosis of SE
The classical definition of SE requires 30 minutes of continuous seizure activity intervening 2 seizures in 30 minutes without intervenng full recovery of consciousness ( Treatment of convulsive status epilepticus: recommendations of the Epilepsy Foundation of America's Working Group on Status Epilepticus. JAMA 1993; 270:854-859). An operational definition proposed by Lowenstein DH requires 5 minutes of continuous seizure activity or 2 seizures without intervening full recovery of consciousness ( Lowenstein DH., Epilepsia. 1999; 40[suppl 1]: S3-8).
SE can be broadly classified into generalized (tonic, clonic, tonic-clonic, myoclonic, absence) or focal (psychomotor/limbic, epilepsia partialis continua, hemiconvulsive SE with hemiparesis, aura continua) depending on clinical &/or electrographic data.
While generalized or partial epileptic convulsive SE, whether overt or subtle, may be easier identified, the definition of non-convulsive SE (NCSE) by EEG criteria alone is still fraught with uncertainties. Young et al proposed EEG criteria for NCSE which gave primary significance to repetitive (for at least 10 seconds) sharp waves at 3 per second or if less than that, clinical improvement after administration of anti-convulsant medications. Sequential (at least 10 seconds) rhythmic activity could also be considered EEG seizure activity if it demonstrated an incrementing onset and decrementing offset (frequency and amplitude) and was followed by post activity slowing or voltage attenuation (Young et al, Neurology 1996; 47:83-9).
EEG patterns like periodic lateralized or localized eptiform" discharges (PLEDs), burst-suppression activity still remain controversial as to whether they are EEG seizures, inter-ictal epileptiform activity or non-epileptiform activity.
Termination of Seizures, Treatment underlying precipitants
After ensuring that the patient's airway, breathing & circulation are secure, management shifts to the prompt termination of seizures. Delay m initiating treatment and inadequate medication dosages are two main causes of treatment failure (Treiman et al; Veterans Affairs SE Cooperative Study Group, N Engl J Med 1998; 339:792-8). Often used first-line medications include intravenous benzodiazepines (diazepam, forazepam), phenytoin and phenobarbitone. Should seizures persist beyond these in adequate doses (often >60 minutes would have elapsed), refractory SE (RSE) could have set in. Before embarking on second-line anti-convulsant agents, the clinical features of the patient's seizures need to be reviewed for possible pseudostatus epilepticus. Second-line agents include intravenous valproate, midazolam, propofol, thiopentone and more recently, oral topiramate. Various algorithms exist to guide physicians in the step-by-step introduction of successive anti-convulsant medications., More agents and more effective agents are urgently needed to boost the current sparse armamentarium of drugs for SE.
Attention should also be accorded to the likely precipitants for SE, including stroke, CNS infections, tumor, toxic-metabolic disturbances, etc...
Treated convulsive SE may still smoulder as NCSE; NCSE may also present as unexplained total or partial unresponsiveness.
The increased usage of continuous EEG (cEEG) monitoring of patients with SE or refractory SE has increased the diagnostic pick-up of NCSE, helped titrate anti-convulsant medications and aided in differentiating non-epileptic movements.
While NCSE may not be associated with as much systemic side effects as its convulsive counterpart, it has been postulated to contribute to significant neuronal damage with long-term sequelae (memory and other cognitive deficits). The outcomes with aggressive treatment of NCSE are still indeterminate.
Complications and Prognosis of SE
Complications that could potentially accompany convulsive SE include hyperpyrexia, acidosis, rhabdomyolysis, hepatorenal failure, hypotention, hypoxia, pulmonary oedema, DIVC and electrolyte abnormalities. These should be pre-empted and the patient accordingly supported.
Higher mortality/morbidity is often associated with the elderly, the presence of underlying cerebrovascular disease, CNS infections, hypoxia or severe metabolic disturbances. Patients with pre-existing epilepsy (SE due to non-compliance to medications, medication change, ...) appear to do better.
DR. ANDREW PAN
The author is a Consultant of Neurology National Neuroscience Institute ; Singapore General Hospital Campus.
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