Second edition

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286 Other major syndromes
Once imaging has been accomplished, and a decision
has been made as to whether treatment with tissue plasminogen
activator (discussed below) should be offered,
further laboratory evaluation is undertaken to determine
the mechanism of the stroke.
In cases of ischemic infarction, the following tests should
be considered: Holter monitoring, echocardiography,
duplex doppler studies of the carotid arteries, and either
MR angiography or CT angiography. Holter monitoring
is required to detect intermittent atrial fibrillation.
Echocardiography may be either trans-thoracic (TTE) or
trans-esophageal (TEE): although TEE is invasive, it is
superior to TTE for imaging the left atrium, left atrial
appendage, any atrial septal defects, and the aortic arch
(Daniel and Mugge 1995; Sen et al. 2004). Duplex doppler
studies identify plaques and stenotic lesions of the carotid
arteries; MRA, and CTA, are likewise useful in this regard
and also allow imaging of the larger intracranial vessels. If
an embolic source is present, it is usually demonstrated by
one or more of these tests. There are, however, exceptions.
In some cases, the entire emboligenic lesion, for example a
small atrial thrombus, may undergo embolization, leaving
nothing behind to detect. Hence, some clinical judgment is
required in interpreting these tests. For example, as noted
earlier, a stroke which is ‘maximal’ at the onset is likely
embolic in nature. Furthermore, ischemic infarction in
one of the distal branches of the cerebral arteries is also
likely embolic: thrombotic infarctions usually occur at
areas of atherosclerotic plaque formation, which, as noted
earlier, are generally in the more proximal portions of the
arterial tree; by contrast, smaller emboli may readily pass
distally to occlude an artery further downstream. Finally, if
there is more than one acute infarction, and these infarctions
are in different arterial territories then an embolic
mechanism is a more likely explanation (Baird et al. 2000):
multiple emboli, say, from a cardiac source, may course up
different arteries, whereas it is unlikely that multiple different
stenotic arteries would simultaneously give off emboli.
In thrombotic infarction, the underlying etiology is usually
atherosclerosis, and one typically finds evidence of hyperlipidemia,
diabetes mellitus, hypertension, or smoking. When
these are absent, or the patient is under 45 years old, other
causes must be considered, as discussed earlier, and consideration
should be given to the following tests: protein S,
protein C, anti-thrombin III, factor V Leiden, anti-cardiolipin
antibodies (IgG and IgM), and lupus anticoagulant. The antiphospholipid
syndrome may occur on an idiopathic basis or
be secondary to systemic lupus erythematosus and, consequently,
in the presence of anti-cardiolipin antibodies or
lupus anticoagulant, an ANA test should also be ordered.
In patients with intracerebral hemorrhage, re-imaging
with MRI (including a T2* sequence to detect evidence of
old petechial hemorrhages in cases of suspected cerebral
amyloid angiopathy) should be undertaken after a few
weeks have passed, by which time enough blood will have
been resorbed to allow the detection of most of the possible
underlying causes.
Patients with spontaneous subarachnoid hemorrhage
require arteriography to demonstrate the source of the
arterial bleeding.
Differential diagnosis
Ischemic infarction may be mimicked by multiple sclerosis
or a Bell’s palsy. Multiple sclerosis is distinguished by
imaging and CSF findings. Bell’s palsy may suggest a ‘pure
motor’ lacunar syndrome but only until recognition that
the forehead is involved declares the lesion to be in the
facial nerve.
Intracerebral hemorrhage may be mimicked by complicated
migraine; however, in complicated migraine the
headache is usually delayed for from 30 to 60 minutes after
the onset of focal signs, whereas in intracerebral hemorrhage,
the headache evolves more or less simultaneously
with focal signs. Epidural or acute subdural hematomas may
likewise mimic an intracerebral hemorrhage, and in the
absence of a history of trauma the diagnosis may depend on
imaging. Hypertensive encephalopathy may closely mimic
intracerebral hemorrhage, with headache, nausea and vomiting,
and seizures. Finding a grossly elevated blood pressure
may or may not be helpful here, as this may be common to
both conditions. Delirium and visual loss favor hypertensive
encephalopathy; however, here the diagnosis often depends
on imaging: although there may be petechial hemorrhages
in hypertensive encephalopathy, one does not see the large,
well-circumscribed collection of blood characteristic of
intracerebral hemorrhage.
Subarachnoid and primary intraventricular hemorrhage,
with the associated hyperacute onset of ‘worst-ever’
headache, are rarely imitated by any other disorder. Both
meningitis and severe migraine might be considered, but
imaging will quickly resolve the issue.
Cerebral venous thrombosis may be mimicked by subacute
subdural hematoma, a brain tumor (e.g., glioblastoma
multiforme) or a cerebral abscess, with, again, imaging
resolving the question.
TIAs may be mimicked, with varying degrees of faithfulness,
by partial seizures, ‘transient tumor attacks’, multiple
sclerosis, transient global amnesia, and either hyperor
hypoglycemia. Inhibitory motor simple partial seizures
are suggested by their exquisitely paroxysmal onset, over
seconds, and by their association with other seizure types.
A post-ictal Todd’s paralysis may also enter the differential
but this is immediately suggested by the history of the preceding
seizure. ‘Transient tumor attacks’ occur in association
with cerebral tumors, which are immediately apparent
on imaging. Multiple sclerosis is suggested by the early
adult onset, and may be confirmed by imaging and CSF
analysis. Transient global amnesia (TGA) is, relative to a
TIA, long-lasting; furthermore, there is no heminanopia or
blindness in TGA, findings that would be expected in a TIA
occurring secondary to ischemia in the area of distribution
of the PCAs. Finally, hyperglycemia (as may be seen in