47.1 Case Description
47.1.1 Clinical Presentation
A 67-year-old man was brought to the emergency department (ED) by ambulance after being found at home with new onset of left hemiparesis and dysarthria. He was last seen well 30 minutes earlier by his wife.
On further history, there was a prior episode of left hemiparesis and dysarthria 2 years ago. The patient’s wife was told it was a stroke, and at the time, he had received tissue plasminogen activator (tPA) with resolution of deficits. No stroke etiology was found. His only home medication was aspirin 81 mg daily.
In the ED, his National Institutes of Health Stroke Scale (NIHSS) score was 5 for mild left hemiparesis (drift in left upper and lower extremity—1 point each), mild dysarthria (1 point), drowsiness (1 point), and left visual extinction (1 point).
His routine stroke laboratory panel was normal, including cell counts, glucose, electrolytes, and coagulation studies.
A noncontrast CT of the head showed old right frontal infarction (Fig. 47.1a). CT angiography (CTA) was normal (Fig. 47.1b). CT perfusion demonstrated a large area of hyperperfusion of the right hemisphere—increased cerebral blood flow (CBF) and cerebral blood volume (CBV) with decreased mean transit time (MTT)—extending beyond the expected middle cerebral artery territory (Fig. 47.1c). Electroencephalography (EEG) later showed a nonspecific area of focal slowing over the right frontal lobe and no active seizure.
Follow-up MRI did not reveal any new infarction corresponding to the perfusion abnormality (Fig. 47.2).
47.1.3 Clinical Reassessment
Ten minutes later, he was found to experience twitching of the left lower face and left thumb, which evolved into a clonic activity of the left arm. His head and gaze deviated to the left. He was given 2 mg of lorazepam intravenously and the movements quickly abated. He then became drowsier. Postictally, the tone in the left hemibody was flaccid, while the tone and power in the right hemibody appeared normal.
One hour later, his deficits resolved entirely.
Seizure secondary to remote right frontal stroke, causing mild postictal paralysis and dysarthria. No evidence of new cerebral infarct.
Lorazepam 2 mg IV aborted the initial seizure. He received phenytoin 20 mg/kg IV (rate <50 mg/min) loading dose in the ED to prevent seizure recurrence acutely.
He was eventually discharged from hospital with a diagnosis of poststroke epilepsy. The following day, he started levetiracetam 500 mg PO BID for long-term seizure prevention. Counselling was provided regarding potential side effects, including mood or behavior changes. Follow-up was booked in the epilepsy clinic in 3 months’ time.
Secondary stroke prevention strategies were reassessed in the light of his remote stroke, and recommendations for ongoing management of this issue were shared with the family doctor.
Cerebrovascular clinicians must become familiar with the bidirectional relationship between strokes and seizures. Seizures can mimic strokes, and strokes can mimic seizures; alternatively, both can coexist in the same patient, either because strokes precipitate seizures or due to a common underlying mechanism.
Seizure as a Stroke Mimic
Among stroke mimics, seizures have been consistently ranked as one of the most common—accounting for 21 to 41% of mimics. 1 , 2 , 3 The International League Against Epilepsy (ILAE) defines seizure as “a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.” 4 Seizures may be considered in four phases: prodrome, aura, ictus, and postictus. Classically, it is the postictal phase that mimics strokes, but other phases may do so less commonly. These will be reviewed in sequence.
The first phase, prodrome, is only recognized in about 20% of patients. 5 Its onset may precede seizures by up to several days. The most common prodromal symptoms are “funny feeling,” “confusion,” “anxiety,” “irritability,” “speech disturbance,” and “headache” in decreasing frequency. Seizure prodrome does not usually mimic cerebral ischemia.
An aura is defined as “a subjective ictal phenomenon that comprises all experienced sensations in a patient and may precede an observable seizure.” 6 The aura often precedes other manifestations of the ictus, but occasionally it is isolated; in other words, a focal seizure may produce only subjective symptoms without evolving into an observable seizure. 7 Typically, an aura lasts seconds to minutes; rarely, it is prolonged— a phenomenon called “aura-continua,” a form of focal status epilepticus. 8 The incidence of auras among patients with epilepsy has ranged from 20 to 94%. 8 The most common specific manifestations of an aura are sensory (visual hallucinations, paresthesias, numbness, pain, and stiffness) and autonomic (gastrointestinal discomfort and palpitations). 6 An epileptic aura is most apt to be confused with an ischemic event when it is prolonged, and/or when it is manifested by purely negative (loss of function) symptoms such as numbness, speech disturbance, or vertigo.
Observable seizures (ictus) may occur with or without preceding epileptic auras. Occasionally, this portion of seizures may mimic cerebral ischemia. The most striking example is when seizures manifest as acute unilateral weakness. 7 , 9 , 10 , 11 Purported responsible cortical regions include the primary sensorimotor area, primary negative motor area, and supplementary negative motor area. 12 Ictal hemiparesis can also be a feature of temporal lobe epilepsy and may be accompanied by ipsilateral automatisms. 11 Speech arrest, aphasia, or other speech changes may be seen with seizures involving the anterior or posterior language areas of the dominant frontal or temporal lobes. 7 , 11 Rarely, other ictal neurologic symptoms or signs—besides weakness or speech disturbances—may mimic strokes. For example, facial apraxia can be seen with frontal opercular seizures—clues to the diagnosis include concurrent facial clonic activity and profuse salivation. 7
Finally, the most common stage in which seizures mimic strokes is the postictal phase. Postictally, hemibody weakness has been called “Todd’s paralysis.” Its incidence ranges from 0.64-32%. 13 Tone may be flaccid, normal, or spastic. Reflexes can be diminished, normal, or increased. Occasionally, there is associated aphasia or gaze palsy, and usually, no other associated major neurologic deficit. Postictal paresis typically lasts around 15 hours, but can be as short as 30 minutes or as long as 36 hours. 14 The duration of weakness does not appear to be related to the duration of the seizure itself. It occurs with every seizure in some patients, and sporadically in others. The pathomechanism of negative neurologic signs postictally is up for debate—some theories include hypoxia from neuronal exhaustion, neurotransmitter depletion, hyperperfusion with AV shunting, or an increase in inhibitory discharges. 12 , 14 , 15
In summary, seizures may be broken down into four phases: (1) prodrome, which does not usually mimic stroke; (2) aura, which occurs at the start of the ictus but has no observable signs and only infrequently mimics stroke; (3) observable ictus, which occasionally mimics stroke; and (4) postictus, which is the most common stroke mimic. Seizures most commonly produce positive neurologic signs (gain of function), but it is when they cause negative (loss of function) signs—weakness, numbness, speech disturbances, or visual loss—that they can resemble cerebral ischemia.
Stroke and Seizure May Coexist
Strokes are the most common underlying cause of seizures among the elderly population. 7 When seizures begin in older individuals without a known history of strokes, occult cerebrovascular disease should be considered. 16 Among all age groups, seizures may occur poststroke in about 10% of patients. 17 They can occur “early”—defined as within 7 to 14 days of the stroke—or they can occur “late.” There is minimal data on the frequency of seizures at the very onset of strokes. When defined as “immediate” or within 24 hours, a study by Szaflarski et al of over 6,000 patients found that about 3% of stroke patients experienced seizures. 17 Seizures are more common after hemorrhagic strokes (intracerebral hemorrhage/subarachnoid hemorrhage [SAH]; 8.4%) than ischemic (2.4%). Among those with ischemic strokes, seizures appear to be more common when the etiology is embolic. 17 , 18
The mechanism of early versus late poststroke seizure likely differs: early poststroke seizure may result from hypoxia and biochemical dysfunction from the excitatory neurotransmitter cascade, while late poststroke seizure is more likely due to structural changes or gliosis, eventually leading to the process of epileptogenesis. 18 , 19 Indeed, late-onset seizures are linked to a greater risk of subsequent epilepsy compared with early poststroke seizures. 18 Although early-onset seizures may be less likely to evolve into epilepsy, they may increase the burden of ischemia by amplifying metabolic demand. 20
47.2.2 Workup and Diagnosis
To determine whether a patient has had a stroke, seizure, both, or neither, collateral historians are usually necessary. The clinician should obtain a history from the patient, as well as the closest witness of the episode, avoiding as much as possible second- or third-hand information that is prone to error. The most proximal witnesses may be strangers, colleagues, friends, or family members.
As of yet, no single symptom, sign, or epidemiologic factor ably predicts whether the patient is presenting with a stroke or a mimic. 21 The physician should obtain a complete description of the event itself, as well as what preceded and followed it. Table 47.1 suggests some important questions to consider asking of the patient and/or witnesses.
The first step in the examination is assessment of stability including vitals. Autonomic dysfunction, including alterations in blood pressure and heart rate, may be seen in either strokes or seizures and may need to be urgently addressed.
The clinician would then ordinarily perform a rapid, standardized screening examination for stroke, the NIHSS. Strokes are not excluded by the presence of seizures on examination, since both can present simultaneously.
Assessment of possible seizures starts like any other neurologic examination with mental status. Impaired awareness is seen with generalized seizures, and occasionally with those of focal onset. 4 It may instead indicate an underlying neurologic or systemic cause for the patients’ presentation. Altered mental status does not preclude a thorough neurologic examination: Even with altered mental status, the clinician should be diligent, as one may uncover subtle, ongoing seizure activity, postictal features, or an underlying explanatory lesion.
Besides mental status, key elements to an examination for seizure include sustained gaze or head deviation, spontaneous unidirectional or bidirectional nystagmus, and any abnormal movements including twitching of the facial muscles, tonic posturing or rhythmic (clonic) jerking, tone, and reflex testing. The clinician should note how these signs evolve over time, as one may note the “gain of function” of the ictus followed by postictal “loss of function,” for example, sustained gaze deviation that switches sides. The clinician should observe whether there are associated automatisms such as picking at clothing, chewing, or rapid blinking.
Bedside funduscopic examination may reveal papilledema, suggesting a mass lesion. Nuchal rigidity may implicate meningitis. Examination of the skin may show signs of infection or an underlying neurocutaneous disorder. Dysmorphisms should be noted. Examination of the tongue may reveal a tongue bite, which is seen in about 22% of epileptic seizures. 22 The patient should be assessed for musculoskeletal injuries.
When presented with possible seizures, laboratory investigations may serve three purposes:
Supporting the diagnosis of seizures versus the differential diagnosis.
Identifying an underlying cause for seizures.
Assessing complications of seizures.
1. Supporting the Diagnosis of Seizures
Four laboratory tests have been found to be helpful in supporting a clinical diagnosis of generalized tonic-clonic seizures when elevated: prolactin, ammonia, lactate, and creatine kinase. None so far have been able to rule out seizures or strokes as the alternative. Each biomarker rises and peaks at different time points, so the clinician must consider this, if one is to ably interpret the test. Sensitivities are low, and multiple variables can affect their levels. Overall, there is a paucity of high-quality evidence to support the routine use of biomarkers in order to confirm a seizure diagnosis. 13 , 22 , 23 , 24 , 25 , 26
2. Identifying an Underlying Cause for Seizures
Seizures may be provoked by metabolic, infectious, endocrine, toxic, autoimmune, and other causes that may be supported by laboratory investigations. The following tests can be considered in the workup for unprovoked seizure: cell counts, glucose, thyroid studies, electrolytes and extended electrolytes, hepatic and renal function, serum and urine toxicologies, and alcohol and drug levels. Lumbar puncture should be considered when intracranial infection or SAH are suspected; otherwise, it is not usually indicated. 22 , 23 , 24