Diagnosis, Treatment and Management of Seizures
R.C. Krishna MD, Consultant Neurologist, New York
(Manipal Alumni, Year of 1982)
Syncope may not be benign in this population. Causes include
- hypovolemia (e.g., blood loss, diuretics)
- decreased arterial or venous tone (e.g., vasodilators, autonomic dysfunction)
- limited cardiac output (e.g., aortic stenosis, arrhythmias)
- inappropriate baroreceptor reflexes (e.g., emotional situations, Valsalva maneuver)
Upright posture at onset and a typical warning of lightheadedness, nausea, warmth, and fading vision and hearing are common but not universal, and stroke patients may have difficulty reporting these sensations. Cardiac arrhythmias, some potentially fatal, may lead to sudden loss of consciousness, even in the supine position. In these patients, palpitations may be noted if onset is not sudden or at other times.
A few myoclonic jerks commonly accompany syncope, and tonic stiffening (as well as more complex movements) may also occur, especially if the head is kept upright. The pathophysiology of such convulsive syncope is release of brain stem activity from cortical influence rather than an electrocortical seizure. In addition, syncope can rarely occur as a vertebrobasilar TIA, especially when flow through one or both carotids is severely compromised.
The episodic headache and other symptoms of migraine sometimes are preceded by an aura, 5 to 60 minutes of cortical or brain stem dysfunction. Migraine auras are distinguished from seizures by their more gradual, often visual, warning and longer duration. Associated symptoms include nausea or vomiting, photophobia, and phonophobia. Headache usually, but not always, follows. “Migraine equivalents” without headache are more common in the elderly and are occasional causes of TIA-like symptoms or of actual TIAs. Loss of consciousness is rare but may occur with so-called basilar migraine.
It must be recognized that migraine and epilepsy can coexist, that headaches often follow epileptic seizures, and that a migraine attack can, rarely, precipitate a seizure.
Migraine is discussed more fully in Migraine and epilepsy.
Transient ischemic attacks (TIAs)
TIAs themselves can be confused with seizures, although they have characteristic symptoms and (if prolonged enough to persist to the time of evaluation) signs consistent with known vascular territories. They typically evolve over minutes and last minutes to hours.
Jackson was first to point out that seizures generally manifest “positive” symptoms, such as stiffening or shaking in the motor system or hallucinations in the special sensory modalities, whereas ischemic symptoms are usually “negative” (e.g., weakness, sensory loss). Exceptions to this rule include ischemic paresthesias, rare motor inhibitory seizures, and “limb-shaking” TIAs.
“Limb-shaking TIAs” are rare manifestations of severe carotid stenosis. They can be distinguished from motor seizures mainly by
- their consistently postural character, usually occurring promptly on standing
- their involvement of arm, leg, or both, sparing facial muscles and cognition
On the other hand, rare seizure types, such as ictal amaurosis (total or hemianopic, not monocular) or aphasic status epilepticus, require EEG to be distinguished from TIAs.
Patients with cerebral amyloid angiopathy have been noted to have transient events for which the underlying pathophysiology has not been established; no evidence of microscopic bleeding, transient ischemia, or epilepsy has been discovered. The duration is more similar to that of TIAs than of the other potential etiologies.
Movement disorders can usually be readily distinguished from seizures because they are typically long-lasting and associated with preserved consciousness. Although usually bilateral, they may be unilateral after infarction, particularly infarction of the basal ganglia, thalamus, or subthalamus.
In patients with depressed mental status, toxic or metabolic processes may at times produce movement disorders, such as extrapyramidal reactions to neuroleptics or multifocal myoclonus in uremia. Although the multifocality is not typical of seizures, and the movements are not time-locked to epileptiform discharges on EEG, such discharges are often present and imply “cortical irritability” that may later be manifest as clear-cut seizures.
Asterixis, an abrupt, repetitive loss of muscle tone during maintenance of certain postures, often occurs in patients with depressed mental status due to hepatic or other encephalopathies. After cerebral or brain stem stroke, it can occur unilaterally, contralateral to the lesion. Its positional nature usually distinguishes it from motor seizures, although rare cases of epileptic asterixis have been reported.
Antiepileptic drugs, especially at toxic levels, also can produce involuntary movements, such as dystonia with phenytoin or tremor with valproate.
Sleep disorders may result in microsleeps or more prolonged sleep attacks due to any cause of hypersomnolence. The most common cause is disrupted sleep from obstructive sleep apnea, a condition which (like stroke) is common among patients with hypertension, atherosclerosis, and obesity. Furthermore, many thrombotic strokes, in particular, occur during sleep and are characterized by patients’ awakening with a new deficit.
The second most common medical reason for sleep deprivation leading to sleep attacks is the movement disorder termed periodic limb movements in sleep. These movements usually involve one or both lower limbs, with dorsiflexion of the ankle and flexion of the knee and hip, and are sustained for 1 to 2 seconds and repeated approximately every one-half minute. This condition is associated with restless legs syndrome, a need to walk around or otherwise move the legs, often in response to a crawling sensation felt when lying in bed or otherwise at rest.
Narcolepsy is a more dramatic but much less common cause of hypersomnolence, usually associated with symptoms of hypnagogic or hypnopompic hallucinations, sleep paralysis, and especially cataplexy. Onset is rare after early adulthood, although symptomatic cases related to brain stem trauma, demyelination, and, rarely, infarction have been reported. Although microsleeps may occur without warning, more prolonged sleep attacks are usually preceded by a subjective feeling of sleepiness. Unlike in complex partial seizures, the eyes are usually closed, and the patient may be awakened with stimulation.
Parasomnias can be difficult to distinguish from nocturnal seizures. The classic parasomnias of slow-wave sleep, sleepwalking, and night terrors are conditions of childhood, although the former sometimes persists into adulthood. They are not associated with stroke. In the population at risk for stroke, nocturnal wandering is more likely to occur after a complex partial seizure, and patients usually return to normal awareness rapidly, if stimulated.
A parasomnia of rapid eye movement (REM) sleep, REM behavior disorder, by contrast, typically begins late in life and may be associated with extrapyramidal syndromes such as Parkinson’s disease. Cases in patients with stroke may be coincidental, given the typical ages for both disorders. These attacks consist of partial arousals from REM with a loss of the usual muscle atonia, resulting in “acting out” of dreams, often in a violent manner that may reflect defensive behavior prompted by a frightening dream. The timing of the spells later in the night, when REM periods are longer, can be a useful clue. Polysomnography with additional EEG electrodes may be necessary to distinguish this disorder from nocturnal partial seizures.
Sleep disorders are discussed more fully in Sleep disorders and epilepsy.
Altered behavior due to toxic-metabolic disturbances usually lasts much longer than changes due to seizures. The possibility of certain causes of encephalopathy (e.g., hyperglycemia, hypoglycemia, hyponatremia, hypocalcemia, hypomagnesemia) precipitating acute symptomatic seizures can further confuse the picture.
The EEG, although typically showing diffuse slowing, can, at times, display multifocal sharp waves or the triphasic wave pattern, which may be difficult to distinguish from the generalized sharp-slow complexes of non-convulsive generalized SE.
These disturbances are discussed more fully in Metabolic disorders and seizures.
Psychogenic nonepileptic seizures
Distinguishing psychogenic nonepileptic seizures (NESs), also known as pseudoseizures or psychogenic seizures, from epileptic seizures is a major undertaking of epilepsy monitoring units. Evidence suggests that this phenomenon is most common in young adults, especially women, but there are few data on the frequency and manifestations in elderly patients, and it may be underdiagnosed.
Patients with a previous psychiatric history are likely to be at higher risk, as may be those with depression or other psychiatric complications of stroke, but data are unavailable.
In general, compared to epileptic seizures, psychogenic NESs display less stereotypy, longer duration, a more waxing and waning nature, and nonphysiologic progression. Eyes tend much more often to be closed during unresponsive periods. Environmental precipitants are more likely and injuries less likely, although there are many exceptions. Unlike epileptic seizures, NES do not arise from sleep, although they may arise from “pseudosleep,” and video-EEG monitoring may be required.
Increased intracranial pressure
Transient increases in intracranial pressure can result in temporary alteration in awareness or, less often, focal neurologic dysfunction. The classic situations are a posterior fossa mass or intermittent obstruction of ventricular flow by a third ventricular tumor, but acute hydrocephalus can occur in patients after subarachnoid hemorrhage or after ischemic or hemorrhagic stroke in the cerebellum.
Patients with cerebral edema as a result of hemispheric infarction are likely to show catastrophic focal deficits followed by progressive obtundation.
Headache is common in all of these scenarios, if the patient is alert and articulate enough to report it.
Causative metabolic abnormalities — A patient with a first epileptic seizure typically has screening laboratory studies to exclude a metabolic or toxic cause for an acute symptomatic seizure.
Laboratory evaluations that are appropriate for the evaluation of a first seizure include electrolytes, glucose, calcium, magnesium, hematology studies, renal function tests, liver function tests, and toxicology screens, although the likelihood of finding a relevant abnormality in unselected patients is low.
Prolactin — Serum prolactin assessment has limited utility as a diagnostic test for epileptic seizures14. The serum prolactin concentration may rise shortly after generalized tonic-clonic seizures and some partial seizures. Typically, a level is drawn 10 to 20 minutes after the event and compared with a baseline level drawn six hours later. Criteria for abnormality are not well established; many investigators use twice the baseline level.
Other seizure biomarkers — Other serum markers have been used to help distinguish epileptic seizures from syncope, psychogenic nonepileptic seizures, and other physiologic events. These include: creatine phosphokinase (CPK), cortisol, white blood cell count, lactate dehydrogenase, pCO2, ammonia, and neuron specific enolase. CPK levels in particular are often elevated after generalized tonic-clonic seizures, but not after partial seizures. The later rise and prolonged elevation, up to 24 hours postictally, makes this test somewhat more useful in the outpatient setting. However, a defined threshold level for abnormality, sensitivity, and specificity remain to be determined for CPK, as for other serum markers.
Lumbar puncture — A lumbar puncture is essential if the clinical presentation is suggestive of an acute infectious process that involves the central nervous system or the patient has a history of a cancer-type that is known to metastasize to the meninges. In other circumstances the test is not likely to be helpful and may be misleading since a prolonged seizure itself can cause cerebrospinal fluid pleocytosis.
Lumbar puncture should only be performed after a space occupying brain lesion has been excluded by appropriate neuroimaging studies.
Electroencephalography — The electroencephalogram (EEG) is an essential study in the diagnostic evaluation of epileptic seizures. If abnormal, the routine, interictal EEG may aid in supporting the diagnosis of epileptic seizures and may also suggest whether a patient has generalized or partial seizures.
Use of sleep deprivation and provocative measures during the test, such as hyperventilation and intermittent photic stimulation, increase the yield.
However, a normal EEG does not rule out epilepsy, and many EEG abnormalities are nonspecific. As an example, diffuse slowing may also occur with a wide variety of encephalopathies or in association with some medications, especially at high dosages. Epileptiform abnormalities are usually more informative than less specific changes.
Specialized Techniques — Specific methods can be employed to improve the detection of IEDs and the sensitivity of the test.
Routine activating techniques — A standard routine EEG usually includes hyperventilation and photic stimulation.
- Hyperventilation increases the rate of generalized discharges in childhood absence epilepsy and other generalized epilepsies. One study in 80 patients undergoing long-term EEG monitoring found that hyperventilation had an activating effect on EEG recording, but only in those patients whose AEDs were being tapered.
- Photic stimulation induces IEDs in some individuals with idiopathic generalized epilepsy, and infrequently in patients with focal seizures arising from the occipital lobe.
Sleep and sleep deprivation — Sleep is a neurophysiologic activator of epilepsy; 20 to 40 percent of epilepsy patients with an initial normal recording will have IEDs on a subsequent recording that includes sleep. Sleep is sometimes captured on a routine EEG, but sleep deprivation increases this likelihood. Sleep is also usually captured on prolonged EEG monitoring and alternatively, can be induced by administration of a sedative, usually chloral hydrate.
When sleep-deprived EEG was compared to 24-hour ambulatory EEG monitoring in 46 patients with “presumed epilepsy”, IED detection was similar (24 versus 33 percent). However, clinical seizures were also captured in 15 percent of the ambulatory EEGs and in none of the sleep-deprived EEG.
It is generally agreed that a follow-up EEG in a patient with possible epilepsy and a normal routine EEG should include sleep. Clinicians can order full or partial sleep deprivation, but it is not clear how much this affects the yield. The choice of test (sleep-deprived, sleep with oral sedation, or prolonged EEG monitoring) should be individualized to the patient’s circumstances. Because sleep deprivation can be quite disruptive and carries some risk of seizure exacerbation, we generally prefer 24-hour-ambulatory EEG studies over sleep-deprived studies.
Video-EEG monitoring — Video electroencephalography (EEG) monitoring is the synchronous recording and display of EEG patterns and video-recorded clinical behavior. Short recordings of several hours can be performed as an outpatient in an EEG laboratory, while longer recordings of 24 hours or more are generally done in a hospital inpatient setting.
Advantages of video-EEG — While considerably more expensive than aEEG, there are several advantages to this test, including the continuous video-monitoring that allows for analysis of both the clinical and electrographic features of a recorded event:
- Staff trained in EEG monitoring may detect seizure activity on remote viewing of the video or EEG at the nursing or monitoring station. They can interact with and test the patient during a spell or seizure aura, and push the event button. This can be very important for characterizing impairment of awareness and subtle lateralizing features, including postictal aphasia or hemiparesis.
- Both video and EEG quality are usually superior with inpatient, monitored recordings. Video cameras in inpatient units usually allow infrared viewing of patients in the dark, as well as remote control of the camera, including zooming in as needed, from the nursing or monitoring station. As a result, when a seizure occurs, subtle clinical features with lateralizing importance can be better appreciated, such as dystonic posturing, eye deviation, facial clonus, postictal nose-wiping, brief Todd’s paresis, etc.
- Video can also help identify artifacts produced by nonseizurerelated rhythmic movements (blinking, chewing, toothbrushing, scratching) that can mimic seizures on EEG
- Electrode application can be more frequently monitored and maintained, limiting artifact. Additional electrodes, such as inferior temporal electrodes, are impractical in the outpatient setting, and can be more easily monitored and maintained in the inpatient setting. These electrodes can provide information that would be unavailable from the standard electrode array
Neuroimaging — A neuroimaging study should be done to exclude a structural brain abnormality if the patient’s first seizure was clearly not a provoked seizure. Brain magnetic resonance imaging (MRI) is preferred over computed tomography (CT) to identify specific lesions such as cortical dysplasias, infarcts, or tumors.
Nevertheless, a brain CT scan is suitable to exclude a mass lesion, hemorrhage, or large stroke under emergency situations or if an MRI is unavailable or contraindicated (eg, in patients with pacemakers, non-compatible aneurysm clips, or severe claustrophobia). Relevant findings included intracranial hemorrhage, brain abscess, and tumor.
In young to middle-aged adults, common MRI findings are mesial temporal sclerosis, sequelae of head injury, congenital anomalies, brain tumors, cysticercosis, and vascular lesions. In the elderly, MRIs often reveal strokes, cerebral degeneration, or neoplasms. However, up to 50 percent of patients, regardless of age, have normal neuroimaging studies. Also, while structural abnormalities on brain MRI or CT usually suggest a symptomatic, focal-onset epilepsy syndrome, these findings should not be interpreted in isolation. Many MRI findings are nonspecific and may be incidental.