Differential diagnosis

Whenever an older patient experiences a transient confusional state, unexplained loss of consciousness, or a fall without a clear environmental or medical explanation, the possibility of seizures must be considered.29,30 Episodic neurologic dysfunction has a wide differential diagnosis, however, with certain conditions being much more common in seniors.

Disorders that are sometimes difficult to distinguish from seizures include:31

  • syncope
  • TIAs
  • migraine
  • sleep disorders
  • paroxysmal toxic-metabolic abnormalities
  • movement disorders
  • psychiatric conditions

Syncope

Potential causes
Syncope in seniors is particularly important to recognize because it becomes both more common and more potentially ominous with aging. Typically, the mean blood pressure must drop suddenly and significantly, usually to less than 50 mm Hg.32 Mechanisms that can cause a sufficient decrease in cerebral perfusion to produce the loss of consciousness and postural tone that characterizes syncope include:33

  • an inappropriate reflex-mediated decrease in heart rate, vascular tone, or both
  • arrhythmias producing decreased cardiac output
  • decreased cardiac output from other causes

The most common manifestation of reflex-mediated syncope is simple vasovagal fainting. It usually follows a strong emotional stimulus and often (but not always) has a strong postural component. Vasovagal fainting is the most common cause of syncope in young people but it may account for only 1% to 5% of cases in seniors.32 Other reflex-mediated causes include carotid sinus syncope, micturition and defecation syncope, and syncope during and after eating.

It is essential to rule out cardiac arrhythmias because they can lead to sudden death if untreated. Both bradycardias and tachycardias may result in syncope. They often coexist in older people.33 Occasionally, however, arrhythmias that occur with altered consciousness may be seizure-induced.34,35

Other potential causes of syncope include medications that result in hypovolemia (e.g., diuretics), decreased venous tone (e.g., nitrates), or decreased systemic resistance (e.g., vasodilators and other antihypertensives). Nondrug causes of these phenomena, including fluid loss and autonomic neuropathy, are also common in seniors.

Syncope can also be caused by a sudden obstruction of blood flow from a pulmonary embolus, or more chronic obstruction from aortic stenosis in the setting of increased demand.

Diagnosis
If the history of the episodes includes a postural component, that supports the diagnosis of syncope. (Even vasovagal syncope can occur in the supine position with sufficient emotional stimulus, however.)

Premonitory symptoms such as palpitations, warmth, diaphoresis, fading vision and hearing, nausea, and diffuse weakness also support a diagnosis of syncope, although all these symptoms also may occur during partial seizure auras. In syncope, they are often of more gradual onset, and the nausea associated with syncope does not typically have the rising component that is so common in seizures of mesial temporal origin. Pallor is more often noted with syncope but may also occur during limbic seizures.

Diffuse stiffening or frank clonic movements may occur with syncope, particularly if the person is maintained in the head-up position.36 With rare exceptions, convulsive syncope does not represent a cortical electrical seizure but occurs with cortical depression, usually manifested on the EEG by diffuse flattening.37 The release of brainstem mechanisms from cortical inhibition is the hypothesized mechanism.

Unlike a generalized tonic-clonic seizure, convulsive syncope is usually followed by little or no confusion or somnolence. Urinary incontinence and tongue biting are occur rarely.

Physical examination should emphasize cardiovascular features. Orthostatic vital signs are sometimes revealing. Ancillary tests worthy of consideration include:38

  • ECG (electrocardiogram)
  • ambulatory ECG (Holter) monitoring
  • echocardiography
  • tilt-table testing (in selected cases)
  • cardiac electrophysiologic studies (in selected cases)

TIAs

TIAs (transient ischemic attacks) are important to recognize because of the impact that treatment can have on the risk of future stroke and myocardial infarction.39,40 Although ischemia generally produces "negative symptoms" such as weakness or visual loss rather than "positive symptoms" such as stiffening, shaking, or visual hallucinations, there are many exceptions.

Among the most dramatic are so-called limb-shaking TIAs associated with severe carotid disease contralateral to the involved leg, arm, or both.39,41 These are rarely bilateral. The face and cognition are spared. Their duration may be seconds to minutes, similar to that of seizures, but unlike motor seizures, these TIAs are consistently postural and respond to endarterectomy rather than antiepileptic drugs (AEDs).

Conversely, seizures manifested by motor inhibition, loss of vision, and aphasia with preserved consciousness are rare but well documented. It can be difficult to distinguish them from TIAs, but the EEG is invaluable in confirming their epileptic origin.42,43

Features of the history supporting a diagnosis of TIAs include:

  • constellations of symptoms consistent with ischemia in either anterior or posterior circulations, or in a "lacunar" distribution
  • prior vascular disease or known risk factors
  • much slower resolution than for seizures (duration up to several hours)

Neurologic examination during symptoms usually confirms a vascular distribution. Bruits may be present.

Vascular and cardiac studies may confirm a suspected location or mechanism.

Neuroimaging studies can be extremely helpful in showing evidence of either prior vascular insults or an active lesion corresponding to the current symptoms. An appropriately placed infarct could also provide the substrate for seizures, however. EEG may be helpful and diagnostic if recorded ictally.

Migraine

Migraine can be difficult to distinguish from epilepsy, and the two processes can coexist. Migraine is more common in younger than in older adults, but migraine may more often occur without headache in seniors.44,45

Migraine auras such as scintillating scotomata, hemianopia, or monocular blindness may be confused more readily with TIAs than with seizures. "Basilar migraine" symptoms, however, can include altered consciousness as well as vertigo, ataxia, and visual disturbances.45 This can mimic a seizure or nonconvulsive status epilepticus.

Sleep disorders

Obstructive sleep apnea is common in seniors, affecting 5% to 10% or more of seniors.46 Nocturnal cardiac arrhythmias may increase the risk of cardiac or cerebral ischemia and of sudden death. The most common consequence of sleep apnea is excessive daytime somnolence, which may greatly affect functioning. Sleepiness can sometimes manifest as "microsleeps," brief periods of unresponsiveness that can be confused with partial seizures. Rarely, intermittent confusion or even apparent dementia can result from excessive sleepiness.

Other causes of poor nocturnal sleep, such as periodic limb movement syndrome, can have similar daytime manifestations.46 Occasionally, the limb movements themselves may be mistaken for seizure activity. Usually they are easy to distinguish because they occur as sustained 0.5- to 5-second movements at 20- to 60-second intervals rather than in a rapid, rhythmic pattern.

Somnambulism and night terrors, the classic parasomnias of slow-wave sleep, may be confused with seizures but are rare in old age.46,47

Nocturnal enuresis, raising the possibility of a nighttime convulsion, may occur in seniors because of a urinary tract infection or other urologic cause. Typically, however, daytime incontinence is also present.

The narcolepsy-cataplexy syndrome generally presents in early adulthood, although it may not be diagnosed until later. Obstructive sleep apnea, which may coexist with narcolepsy, is a much more common cause of daytime somnolence in seniors, however.

Attacks of "paroxysmal nocturnal dystonia" are likely to represent frontal lobe seizures.46

Rapid eye movement (REM) sleep behavior disorder is a recently recognized parasomnia that occurs most commonly in elderly men. It consists of sudden arousals from REM sleep that are immediately followed by complex and often violent behavior (at times appearing directed), although the patient is unresponsive and amnestic for these periods. There is a significant risk of injury to the patient or bed partner. These behaviors are often construed as defensive activity related to dreaming, with loss of the somatic atonia that is normally present during REM sleep and dreaming. These episodes are easily misinterpreted as complex partial seizures or postictal agitation.47

Polysomnography is essential for diagnosis of sleep apnea, periodic limb movements, and parasomnias. In most laboratories it is possible to perform more complete EEG recording than the minimum needed for sleep staging, and this should be done when nocturnal seizures are considered.

The multiple sleep latency test is a means of quantifying daytime sleepiness. It is essential in diagnosing narcolepsy and can be helpful in assessing the effects of other sleep disorders on daytime alertness.

Toxic-metabolic disturbances

Most toxic-metabolic disturbances produce a long-lasting confusional state that does not strongly suggest an isolated seizure, although nonconvulsive status epilepticus48-50 or a prolonged postictal state should be considered. The picture may be confused by myoclonus, which can occur in many electrolyte disturbances, intoxications, uremia, and sepsis.

The EEG may show sharp activity, although usually not frank spikes and not a dominant focus unless there is preexisting focal illness. The triphasic wave pattern, most strongly associated with hepatic encephalopathy, is also often seen in uremia. postanoxic coma, and other encephalopathies. At times, this pattern can be difficult to distinguish from the generalized sharp-slow or even frank spike-wave complexes of nonconvulsive generalized status epilepticus, which could clinically resemble a metabolic encephalopathy as well.51

In doubtful cases, benzodiazepine infusion can be helpful if both the EEG and the patient improve, although this test is not always easy to interpret in practice.

The clinical manifestations of glucose abnormalities, particularly hypoglycemia in patients who are taking insulin or hypoglycemic agents, may be brief. Typically, the patient exhibits anxiety, tremor, sweating, and tachycardia consistent with sympathetic nervous system activation, but at times loss of consciousness and even true convulsive seizures may occur. Nonketotic hyperglycemia can cause focal myoclonus and true focal or generalized seizures, as can uremia.

Movement disorders

Movement disorders may be mistaken for motor seizures. Characteristics of movement disorders include:

  • preserved consciousness
  • usually bilateral
  • generally not episodic, although they may wax and wane

High doses of AEDs may actually produce movement disorders in some patients. For example, valproate commonly causes a dose-related tremor, and phenytoin rarely produces dystonia.

Psychiatric disorders

Although psychiatric disorders, particularly depression, are common in seniors, new-onset psychogenic nonepileptic seizures are probably rare. This has not been carefully studied, however.

Before making this diagnosis, rule out physiologic nonepileptic events such as those described above. Use video-EEG monitoring to look for ictal or postictal EEG change.52 Verify that the events do not resemble seizure types during which a negative surface EEG recording is common, such as simple partial or frontal lobe seizures. Placebo induction may also have a place in diagnosis.

Adapted from: Bromfield EB. Epilepsy and the elderly. In: Schachter SC, Schomer DL, eds. The comprehensive evaluation and treatment of epilepsy. San Diego, CA: Academic Press; 1997. p. 233-254.
With permission from Elsevier (www.elsevier.com).

Authored By: 
Edward Bromfield MD
Steven C. Schachter MD
Donald L. Schomer MD
I<