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Case Presentation This presentation will address the following questions: 1. What historical or physical examination findings suggest an ischemic stroke? 2. What processes may simulate stroke? 3. What are some unusual stroke presentations? TOPStroke Differential Diagnosis - Mimics and Chameleons Introduction
The diagnosis of acute ischemic stroke is often straightforward. The sudden onset of a focal neurologic deficit in a recognizable vascular distribution with a common presentation - such as hemiparesis, facial weakness and aphasia - identifies a common syndrome of acute stroke. But differential diagnostic problems remain because there are several subtypes of stroke and also because some non-vascular disorders may have clinical pictures that appear identical to strokes. This talk will briefly review the differential diagnosis of stroke starting with stroke sub-types. Stroke “mimics,” non-vascular conditions that simulate stroke, will then be covered in detail. The final discussion addresses unusual clinical pictures that may result from stroke which here are termed stroke “chameleons” - strokes that take on the appearance of something else. Stroke
Subtypes The abrupt presentation of acute ischemic stroke results from the
abrupt interruption of blood flow to a part of the brain. Most commonly
this is from embolic or thrombotic arterial vascular occlusion that
may be visualized angiographically in many cases when symptoms are
severe enough to warrant acute angiography.1 Other vascular
events which may result in stroke syndromes include lacunar strokes,
arteritis, arterial dissections, and cortical venous occlusions. Intraparenchymal
intracranial hemorrhage from a variety of causes - the spontaneous
or hypertensive hemorrhages, vascular malformations, or aneurysmal
origin - are frequently encountered clinically and figure prominently
in the initial stroke differential diagnosis. These different processes
may be considered stroke subtypes for classification purposes and
are listed in the first section of Table 1.
The terminology “misclassified” stroke has recently been used to
describe patients initially thought to have stroke but later found
to have hemorrhage, lacunar infarction, or posterior circulation ischemia
after extensive imaging that included magnetic resonance imaging (MRI),
magnetic resonance angiography (MRA), diffusion-weighted imaging (DWI),
and perfusion-weighted imaging (PWI). One study found that 21% of
patients thought to have had anterior circulation ischemic stroke
at initial evaluation had other stroke types that had been misclassified.2
As more advanced imaging techniques move into clinical practice, diagnostic
accuracy of assignment to stroke sub-types will continue to improve. Stroke
Mimics
Background
and Studies
Stroke mimic is the term employed for manifestations of nonvascular
disease processes when a strokelike clinical picture is produced.
The presentation resembles or may even be indistinguishable from an
ischemic stoke syndrome. The mimics include both processes occurring
within the CNS and systemic events. Distinguishing these noncerebrovascular
stroke mimics from strokes is increasingly important in this era of
interventional stroke therapies with potential adverse effects.
Stroke mimics may be discovered at different points in clinical investigation;
obviously a listing of alternative diagnoses or mimics based on the
initial working diagnosis of stroke after history and physical examination
only will differ from final diagnoses when the mimic is discovered
after extensive neuroimaging and laboratory work. That many clinical
conditions could simulate stroke has been known for years, but studies
done with the advent of neuroimaging perhaps allowed the first estimate
of the frequency of stroke mimics. One early study of patients admitted
with an initial diagnosis of cerebrovascular disease found that 30%
had unsuspected intracranial lesions; in all fairness, this included
patients with slower progression of neurological impairment (“generalized
cerebrovascular disease” was the terminology) as well as more acute
presentations.3
A more recent article by Libman and colleagues looked at variables
to determine if they could discriminate between stroke and strokelike
pictures.5 They looked at consecutive patients presenting
to an emergency department with an initial diagnosis of stroke over
a two year period. The definition of stroke was the sudden onset of
a focal deficit by history or physical examination lasting more than
one hour. The initial diagnosis was made by an acute stroke team that
consisted of neurologists, emergency physicians, and specially trained
nurses; emergency physicians made the initial diagnosis in about 75%
of cases. The initial diagnosis was made before computed tomographic
study. Both ischemic and hemorrhagic strokes were classified as “true
strokes” in their study. Of the slightly more than 400 patients initially
diagnosed as stroke, 19% were found to have mimics. Four conditions
comprised the majority of the mimics in this study: unrecognized seizures
with postictal deficits (17% of mimics); systemic infections (17%);
brain tumor (15%), and toxic-metabolic disturbances (13%). There were
fourteen other diagnoses, which included positional vertigo, trauma,
subdural hematoma, and syncope (see table 2 for full listing). Their
analysis showed that decreased level of consciousness and normal eye
movements increased the odds of a stroke mimic being present while
abnormal visual fields, initial diastolic blood pressure greater than
90 mmHg, atrial fibrillation, and history of angina decreased the
odds of mimic being present. With multivariate logistic regression
analysis, only decreased level of consciousness was found to be associated
with increased likelihood of a stroke mimic rather than a true stroke
being present. This reflects the decreased alertness that may be present
with the common stroke mimics of postictal states, infections, and
toxic-metabolic disturbances. A history of angina independently predicted
the presentation was a bona fide stroke, likely reflecting the association
between cerebrovascular and cardiovascular disease.
Kothari and associates reviewed admission diagnosis of stroke (ischemic
and hemorrhagic) for over four hundred patients evaluated in an emergency
department and admitted to a hospital; they then compared the admitting
and discharge diagnoses and found agreement in 96% of cases.6
The admitting diagnoses were assigned after CT study and laboratory
studies. In this study, there was disagreement of the admitting diagnosis
of ischemic stroke or TIA and final discharge diagnosis in 4% of cases
(see table 3). Of the patients misclassified at admission as having
ischemic stroke or TIA, final diagnoses included paresthesias or numbness
of unknown cause, seizure, complicated migraine, peripheral neuropathy,
cranial nerve neuropathy, and psychogenic paralysis. They concluded
that emergency physicians at this urban teaching hospital could accurately
identify patients with stroke, particularly hemorrhagic stroke.
One recent small study used extensive imaging including magnetic
resonance imaging (MRI), magnetic resonance angiography (MRA), diffusion-weighted
imaging (DWI), and perfusion-weighted imaging (PWI) to investigate
patients thought to have anterior circulation stroke. They found that
9% of patients initially diagnosed with stroke were
“misdiagnosed” which they defined as completely normal detailed
MR studies with a probable alternative clinical diagnosis. The alternative
clinical diagnoses included metabolic abnormalities, hemiplegic migraine,
psychogenic, and alcohol withdrawal.2
Diffusion-weighted
MRI was used to investigate almost 800 patients during stroke-like
events in a study by Ay and colleagues.7 They found that
3.5 % of the patients with enduring deficits thought to have ischemic
stroke had normal diffusion-weighted MRI. Roughly two-thirds of this
group ultimately had an ischemic event; ten patients (1.3%) were thought
to have stroke mimics, which included migraine, seizures, functional
disorder, transient global amnesia, and brain tumor (table 4). Further
studies using MRI techniques of diffusion-weighted imaging and perfusion-weighted
imaging will undoubtedly be forthcoming.
It is clear that the incidence of stroke mimics in any study depends
upon the time that the acute stroke syndrome is assessed. In the study
by Libman, when the initial assessment was made after history and
physical examination alone, a stroke mimic was present in 19% of cases.5
In the study by Kothari, when the assignment of stroke syndrome was
made after routine laboratory work and CT scanning, the incidence
of stroke mimics was about 4%.6 The study by Ay which employed
MRI techniques in addition to laboratory work and CT scanning dropped
the incidence of mimics to between 1-2%.7 There are technical
limitations in detecting cerebral ischemia using these techniques,
but each intervention, be it laboratory, CT, or MRI, increases the
specificity of the diagnosis of ischemic stroke. Specific Mimics
That transient hypoglycemia may produce a strokelike picture with
hemiplegia and aphasia has been known for years.8 These
patients may be drowsy but are often alert and do not show the more
common response to hypoglycemia of confusion, diminished level of
consciousness, or coma.9 Aphasia may make the history of
diabetes more difficult to discover. The syndrome has also been reported
in alcoholics with hypoglycemia.10 The pathogenesis of
this focal CNS dysfunction is unclear. Hypoglycemia is generally defined
as a blood glucose level of less than 45 mg/dl in these studies. The
wide use of bedside rapid laboratory testing for glucose now makes
this easily detectable and treatable. The hemiplegia may resolve immediately
with the administration of intravenous glucose but resolution over
a hours is also reported.11
Subdural hematoma, cerebral abscess, primary CNS tumors, and metastatic
tumors are among the clinical conditions simulating stroke in the
studies cited above. The typical clinical presentation of a slowly
increasing mass is a progressive syndrome; an abrupt onset of symptoms
of these masses seems counter-intuitive. A review of patients with
brain tumors presenting to an ED showed that 6% of patients had symptoms
that were of less than one day’s duration; it was thought that these
patients with brief symptom duration might reflect a sub-population
who suffer acute deterioration from hemorrhage into the tumor or who
develop obstructive hydrocephalus.12 Secondary effects
of mass or edema on cerebral vasculature have been identified as possible
causes of abrupt onset of seizures as well. Chronic subdural hematoma
has been frequently reported as a cause of stroke and TIA-like symptoms.13
Seizures
and Postictal States
Every study identifying stroke mimics identifies seizures and post-seizure
events as common causes of stroke-like conditions. Traditional thought
is that these postictal symptoms are manifestations of seizure-induced
alterations in neuronal function that are reversible; structural neuronal
alterations are not present. The postictal weakness or Todd’s paralysis
usually follows partial motor seizures but may follow generalized
seizures as well. Duration is usually brief but may last 48 hours.14
Rare inhibitory seizures with extremity weakness as a manifestation
of the seizure event have been reported as well.14 Seizures
may also present as a complication of acute stroke or develop in a
patient with a history of stroke.15 Most studies have identified
postictal states indirectly after further seizures were observed or
additional history was obtained that suggested a history of seizure
disorder.
Migraine may actually precipitate a stroke, but there is also a variant
of migraine, hemiplegic migraine, where unilateral hemiparesis outlasts
the headache. This is difficult if not impossible to diagnose correctly
at first presentation when it must be regarded as a diagnosis of exclusion;
only with recurrent, stereotypic attacks can this be suspected. Cases
with alternating hemiplegia have been reported. At times this disorder
has been shown to be familial.
Little is written about a factitious or feigned stroke yet several
studies discover rare patients initially thought to have cerebrovascular
disease but later determined to have a functional cause of the hemiparesis
or other stroke syndrome. Conversion disorder is the most commonly
assigned psychiatric disorder. One study of emergency department presentations
of conversion disorder noted that symptoms of paresis, paralysis,
or movement disorders were common and were a presentation in almost
30% of patients.16 They noted significant comorbidity in
this population, often other psychiatric disorders, and emphasized
that conversion disorder is a diagnosis of exclusion. Patients often
undergo multiple diagnostic tests before the diagnosis is assigned.
Hyperglycemia with hyperosmolar state may be associated with focal
neurologic deficits simulating stroke but focal seizures are reported
in this condition as well. Focal neurologic signs with hyperglycemia
may include aphasia, homonymous hemianopia, hemisensory deficits,
hemiparesis, unilateral hyperreflexia, and the presence of a Babinski
sign.17 Other metabolic encephalopathies reported to cause
strokelike conditions include hyponatremia and hepatic encephalopathy.18,
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Stroke Chameleons Strokes with atypical presentations that take on the appearance of other disease process may be termed stroke chameleons, for like the chameleon, these disguised strokes may change and evolve with time. The clinician is left with the daunting problem of discovering the unusual manifestation of an uncommon clinical process. A seemingly infinite number of unusual clinical syndromes have been attributed to ischemic stroke after thorough investigation. The presence of historical risk factors for cerebrovascular disease and the abrupt onset of symptoms may be the best clues available to the emergency physician to detect these unusual stroke syndromes. A few of clinical importance will be briefly summarized. Most strokes present as a deficit or loss of function. Uncommonly,
movement disorders will present from a focal lesion such as ischemic
stroke or hemorrhage. Acute hemiballismus, or unilateral dyskinesis,
often result from acute vascular lesions in the subthalamic nucleus
or connections.20 The movements may vary from wild flinging
movements to mild uncontrollable unilateral movements. The key to
diagnosis is the abrupt onset of symptoms and risk factors for cerebrovascular
disease. A review notes that any kind of dyskinesia, hypokinetic as
well as hyperkinetic, may be found from lesions at many different
levels in the frontal motor cortical and subcortical regions.21
Confusional states, agitation, and delirium have all been reported
as a consequence of focal neurologic injury; structures involving
the limbic cortex of the temporal lobes and the orbitofrontal regions
are commonly involved.22 These states must be distinguished
from the neglect syndromes and fluent aphasias in which patients are
often reported as confused but careful
examination demonstrates a clear focal deficit. Particularly
in syndromes of visual neglect, testing for visual fields will reveal
a dramatic field cut that the patient cannot report since they are
unaware of the deficit.
Sensory complaints of either unusual sensations or loss of sensation
are common in parietal and thalamic strokes. At times the sensory
manifestation of a stroke may take on the characteristics of another
clinical condition. Chest pain and limb pain that mimicked that of
myocardial infarction were reported in a small series of patients;
most had thalamic strokes but one had a lateral medullary infarct.23
Sensory symptoms may occur with lesions in many places in the central
nervous system; cortical involvement is usually accompanied by other
neurologic deficits such as hemiparesis, aphasia, hemineglect, or
visual field abnormalities.24 Cortical blindness is unusual but may occur and may be distinguished from bilateral ocular disease by the normal pupillary light responses and normal optic disks. As many as 10% of patients with cortical blindness deny visual symptoms (Anton’s syndrome); at times there is an element of “blindsight” where patients retain some remnant visual ability in their blind areas. For example, patients with blindsight may make correct ‘guesses’ about movements or colors of objects in the visually deficient areas demonstrating some remnant perception of which they are not consciously aware.25
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