Introduction
This chapter deals with focal brain ischemia, either transient ischemic attack (TIA) or ischemic stroke. Causes, mechanisms, and clinical syndromes of brain hemorrhage are described elsewhere. This chapter is divided into three parts. The first part focuses on an uncommon mechanism of focal brain ischemia, which is low flow. Most TIA and ischemic strokes are caused by embolism or in situ artery occlusion. Hemodynamic causes of focal brain ischemia are less common. Second, uncommon clinical presentations of focal brain ischemia are described. In the third part, uncommon causes of TIA and ischemic stroke are presented together with associated clinical syndromes.
Uncommon Mechanism of Stroke: Low Flow
Ischemic Strokes and Transient Ischemic Attacks Caused by Low Cerebral Flow – Anterior Circulation
Most ischemic strokes and transient ischemic attacks are caused by embolic and acute, in situ (usually thrombotic) occlusion of an artery in the brain. However, in some patients, severe stenosis or occlusion of carotid or vertebral arteries may cause a critical reduction of blood flow, particularly when collateral circulation is compromised because the circle of Willis is incomplete or diseased. Mechanisms to compensate for the reduction of blood flow are vasodilatation by autoregulation and an increase of the oxygen extraction fraction. If the vascular bed is maximally dilated, the supplied brain is particularly vulnerable to any reduction in perfusion pressure. Under these circumstances a small drop in systemic blood pressure may cause transient or permanent focal ischemia.
Boundary-Zone Infarcts
The evidence that at least some boundary-zone infarcts are caused by low flow rather than acute arterial occlusion is that a sudden, profound, and relatively prolonged hypotension (e.g. as a result of cardiac arrest or cardiac surgery) sometimes causes infarction bilaterally in the posterior boundary zones between the supply territories of the middle cerebral artery (MCA) and the posterior cerebral artery. The clinical features include visual disorientation, agnosia, or amnesia. Hemianopia is the most common symptom in unilateral posterior boundary-zone infarction, usually with macular sparing and predominating in the lower quadrant. Brachiofacial hypoesthesia is frequent, while motor weakness is rare and remains mild. In the dominant hemisphere, lesions manifest as either isolated word-finding difficulty or transcortical sensory aphasia (impaired comprehension, but preserved word repetition and speech output). In the non-dominant hemisphere, contralateral hemispatial neglect and anosognosia are usually found. Anterior boundary-zone infarction can occur in connection with severe carotid stenosis or occlusion. The boundary zone is located in the frontoparasagittal region, between the supply territories of the MCA and the anterior cerebral artery in the frontoparasagittal region. The clinical features are contralateral weakness affecting the leg more than the arm and sparing the face, some impaired sensation of the same distribution, and transcortical motor aphasia (intact comprehension and repetition with impaired speech output), which may be preceded by mutism if the dominant hemisphere is infarcted. There is also an internal or subcortical boundary zone localized in the corona radiate and centrum semiovale, lateral and/or above the lateral ventricle. This region lies between the supply areas of the lenticulostriate perforating branches from the MCA trunk and the medullary perforating arteries which arise from the cortical branches of the MCA, the anterior and posterior cerebral arteries. Infarction in this internal boundary zone causes usually a lacunar or partial anterior circulation syndrome and is associated with severe carotid disease and sometimes with an obvious hemodynamic precipitating cause. A drop in cerebral perfusion pressure as a cause of focal brain ischemia should be suspected if the symptoms start under certain circumstances [1]:
on standing up very quickly, even if postural hypotension cannot be demonstrated in the clinic
immediately after a heavy meal
in very hot weather
with exercise, coughing, or hyperventilation
during Valsalva maneuver (but embolism is another possibility)
during a clinically obvious episode of cardiac dysrhythmia (chest pain, palpitations, etc.), but embolism from heart is also possible
during perioperative hypotension
if the patient has recently been started on or increased the dose of any drug lowering blood pressure.
Limb-Shaking TIA
A transient ischemic attack which is typically associated with severe large artery disease with exhausted hemodynamic reserve is “limb-shaking TIA.” It is characterized by 30–60-second episodes of repetitive jerking movements of the contralateral arm and/or leg and has been described with carotid occlusion, but also with stenosis of intracranial vessels, e.g. middle cerebral artery or anterior cerebral artery. “Limb-shaking TIA” is elicited in situations which dispose to low flow, e.g. orthostatic dysregulation, hyperventilation in Moyamoya disease, or by carotid compression. The symptoms usually point towards a seizure-like activity and are often misdiagnosed as focal seizures. In contrast to seizure activity, limb shaking shows no somatotopic spread of movement activity (no Jacksonian march) and usually has a low frequency (about 3 Hz). It is reported that limb shaking disappears with revascularization, e.g. carotid endarterectomy or extracranial–intracranial bypass (Figure 10.1).
A transient ischemic attack which is typically associated with severe large artery disease with exhausted hemodynamic reserve is “limb-shaking TIA.”
Figure 10.1 Limb-shaking TIA. A 55-year-old woman with risk factors (metabolic syndrome, smoking) presented with a limb shaking of the left leg when standing. The right internal carotid artery (ICA) was occluded. Occlusion was presumably acute. Territory of the ICA was supplied from the left ICA via the anterior communicating artery. There was no collateral blood flow from the posterior communicating artery. Initially, the symptom was considered to be focal epileptic. Perfusion MR showed reduction of blood flow in the anterior territory of the right middle cerebral artery and the right anterior cerebral artery.
Ischemic Ophthalmopathy
Another symptom of low cerebral blood flow is monocular transient retinal ischemia occurring when looking into bright light. For patients, objects appear bleached and a brief visual loss may follow. This symptom has been related to retinal claudication: an increase in the metabolic demand during exposure to bright light cannot be met because of an already marginal perfusion. Ischemic ophthalmopathy is a specific, concomitant disorder of uncompensated, critically reduced perfusion pressure due to internal carotid artery occlusive disease. Typically, a gradual, progressive loss of visual acuity, occasionally with bouts of obscuration, is reported leading to a slowly progressive, irreversible damage of the retinal neuronal layer. Further characteristic findings are neovascularization of the retina and iris (rubeosis iris) [2].
Ischemic Strokes and Transient Ischemic Attacks Caused by Low Cerebral Flow – Posterior Circulation
Rotational Vertebral Artery Occlusion and Stroke
Rotational vertebral artery occlusion (RVAO) is caused by mechanical compression of vertebral arteries during head rotation. The vertebral artery is usually compressed at the atlantoaxial C1–C2 level. Tendinous insertions, osteophytes, or degenerative changes resulting from cervical spondylosis may be the cause of this compression. Most RVAO patients exhibit an ipsilateral stenosis or vessel malformation (e.g. hypoplasia) and a contralateral dominant vertebral artery. With ispilateral head rotation, the (contralateral) dominant vertebral artery is compressed. The leading symptom is vertigo, followed by tinnitus. Video-oculography showed that RVAO is associated with a mixed downbeat torsional and horizontal beating nystagmus which may spontaneously reverse direction [3]. The labyrinth is predominantly supplied by the internal auditory artery, which is usually a branch of the anterior inferior cerebellar artery (AICA). As AICA usually takes off the basilar artery at its lower portion, reduced blood flow from the vertebral artery would result in ischemia. Approximately 50% of RVAO patients treated conservatively suffered from infarction or residual neurological deficits [4]. Brief episodes of rotational vertigo can also be caused by compression of the vestibular nerve due to close contact with intracranial vessels, particularly the posterior inferior cerebellar artery (PICA).
RVAO is caused by mechanical compression of vertebral arteries during head rotation. The leading symptom is vertigo followed by tinnitus.
Drop Attack and Vertebrobasilar Ischemia
“Drop attacks” are episodes of sudden loss of postural tone which cause the subject to fall to the ground without apparent loss of consciousness. The attack occurs without warning and is not induced by a change of posture or movement of the head. The patient may be unable to rise immediately after the fall despite being uninjured. Not a single patient in the New England Medical Center Posterior Circulation Registry had a drop attack as the only symptom of posterior circulation ischemia [5]. In vertebrobasilar ischemia sudden falls are usually preceded by and associated with symptoms such as vertigo, diplopia, or blurred vision (Figure 10.2). A “drop attack” has been described in a patient with parasagittal motor cortex/subcortex ischemia in the territory of both anterior cerebral arteries [6].
Figure 10.2 Drop attack. An 82-year-old woman with insulin-dependent diabetes mellitus suffered from recurrent short episodes with nausea, vertigo (sensation of being turned around), sweating, blurred vision, weakness and sudden falling without losing consciousness. Episodes were particularly frequent after reduction of elevated blood pressure. Stenosis of the basilar artery proximal to the AICA (anterior inferior cerebellar artery) was assumed to be the cause of these drop attacks. Symptoms disappeared after stent-PTA of the stenosis.
In “drop attacks” a sudden loss of postural tone causes a fall to the ground without loss of consciousness.
Subclavian Steal Syndrome and Hemodynamic Effects of Proximal Vertebral Artery Disease
Most patients with subclavian artery stenosis or occlusion are asymptomatic. In a large series, only 15 out of 324 patients (4.6%) had objective signs of brachial ischemia such as aching after exercise or a cold upper extremity. Among 116 patients with unilateral steal shown by ultrasonography none had symptoms of brain ischemia [7].
Among more than 400 patients with posterior circulation TIAs or ischemic stroke only two had symptoms (TIAs) attributable to significant subclavian or innominate artery disease [8]. Symptoms which have been associated with decreased anterograde flow or retrograde flow in the vertebral artery are episodes with dizziness, diplopia, decreased vision, or oszillopsia. These attacks are brief and may be elicited by exercise of the arm. A left-to-right difference of radial pulses or of blood pressure are reliable signs which indicate subclavian steal syndrome. Causes of stenosis or occlusion of the vertebral artery are: arteriosclerosis, Takayashu disease, temporal arteritis, or mechanical trauma, as have been reported by bowlers or baseball pitchers.
Most patients with subclavian artery stenosis or occlusion are asymptomatic. Associated symptoms may include episodes with dizziness, diplopia, decreased vision or oszillopsia.
Severe stenosis or occlusion of the proximal vertebral artery is more likely to be caused by embolism than by hemodynamic effects: among 407 patients in the New England Medical Center Posterior Circulation Registry, 80 patients had severe stenosis or occlusion of the proximal vertebral artery. In 45 of the 80 (56%) embolism was the most likely cause of cerebral ischemia. Only in 13 of 80 patients hemodynamic effects were considered to be the cause of cerebral ischemia. Twelve of these 13 patients had severe bilateral occlusive disease of the vertebral artery [8].
Hyperviscosity and Low Flow
Blood flow in the brain is determined by the size of blood vessels, blood pressure, and hemorrheological factors of the blood. Abnormal changes of blood plasma with hematological disease (e.g. Waldenstrom’s macroglobulinemia or paraproteinemia), increase in cell counts (e.g. in diseases such as polycythemia vera, erythrocytosis, or hyperleukotic leukemias), and decreased red cell deformability (sickle-cell anemia, spherocytosis, hemoglobinopathies) lead to a hyperviscous state [9].
Cerebral blood flow is diminished with high hematocrit as found in e.g. polycythemia vera. Symptoms are often unspecific, such as headache, dizziness or vertigo, paresthesias, blurred vision, or tinnitus. Low blood flow and/or increased coagulability may be the cause of focal brain ischemia. Different ischemic patterns have been described, such as lacunar infarction, boundary zone infarction, Binswanger’s disease, or large artery (territorial) infarction. In sickle-cell anemia, deformability of red cells is decreased. This may cause damage in the microcirculation, particularly in the boundary zones between major arterial territories. But large artery occlusive disease, occasionally with the development of Moyamoya syndrome, was also found. Plasma hyperviscosity syndrome is a clinical entity with mucous membrane bleeding, blurred vision, visual loss, lethargy, headache, dizziness, vertigo, tinnitus, paresthesias, and occasionally seizures.
Abnormal changes of blood plasma lead to a hyperviscous state and cerebral blood flow can be diminished. Symptoms are often unspecific, such as headache, dizziness or vertigo, paresthesias, blurred vision or tinnitus.
Uncommon Clinical Presentations of Stroke
The Capsular Warning Syndrome
A small infarct in the internal capsule is considered to be caused by the occlusion of a single lenticulostriate artery which arises from the main stem of the middle cerebral artery (MCA). This infarct typically presents with “pure motor hemiparesis.” The term “capsular warning syndrome” describes the phenomenon in which the infarct may be preceded by repetitive, stereotypic transient ischemic attacks with “pure motor hemiparesis” (“lacunar TIAs”). This burst of hemiplegic TIAs is limited in time and lasts about 24–48 hours. The risk of developing a lacunar infarct is about 40% within the next few days. In situ small-vessel disease (microatheroma or lipohyalinosis) is considered to be the most likely mechanism. Alternatively, it has been suggested that an atheroma in the MCA may cause a high-grade obstruction at the origin of the single lenticulostriate artery [10] (Figure 10.3).
Figure 10.3 Capsular warning sign. A 65-year-old with hypercholesterolemia was referred to the hospital because of a sudden weakness of left face, arm, and leg. He was unable to walk. He was dysarthric. Symptoms disappeared after about 10 minutes, but over the next 5 hours he had four further identical episodes lasting for several minutes. The next day he suffered a lacunar stroke in the internal capsule with persisting pure motor hemiparesis. It is assumed that the occlusion of a single perforating artery (lenticulostriate artery) was the cause of the lacunar infarct.
Bilateral Blindness: “Top of the Basilar Artery”
Sudden cortical blindness is a rare symptom of TIA or stroke and has been explained by an occlusion of the “top of the basilar artery” at the origin of the posterior cerebral arteries [11]. The visual field defects may be quite asymmetric and variable. Symptoms may be transient (TIA) or persisting. Even when severe cortical blindness is present, patients may retain some ability to avoid bumping into objects and may blink to visual threat. This so-called blind sight is probably explained by some sparing of the visual cortex and by preservation of the so-called second visual system, which is composed of the superior colliculi and their projections to peristriate cortex (Figure 10.4). Embolism from the heart or the proximal vertebrobasilar artery is the usual cause of cortical blindness [12]. Other symptoms of bilateral ischemia in the territory of the PCA may be: memory loss, usually involving both anterograde and retrograde amnesia or hyperactive delirium. In cases of persistent amnesia, bilateral infarctions of the mesial temporal lobe have been described [8].
Figure 10.4 “Blind sight.” A 65-year-old patient with known Parkinson’s disease and vascular risk factors (diabetes mellitus, hypertension, obesity, and smoking) suddenly lost muscle tone and consciousness. On admission he was awake, responded to verbal commands, and was partially oriented. Pupils were mid-dilated, response to light was reduced. He reported not seeing anything with either eye. There was no weakness of the limbs. Although without conscious visual perception he was able to unconsciously prevent himself from bumping into objects when walking. When showing him different numbers of fingers he mentioned not seeing the fingers, but his performance of rating the number of presented fingers was much above chance. CCT showed a bilateral infarction in the territory of the posterior cerebral artery with hemorrhage on the right side. The primary visual cortex of each side was damaged.
Bilateral blindness can be due to occlusion of the basilar artery at the bifurcation to the posterior cerebral arteries.
Amnesia
Personal (autobiographical) memories depend on the ability to encode, store, and retrieve information which we consciously experience (“autobiographic episodes”). The cognitive system representing this ability is termed “episodic memory.” It can be tested by questions about recent personal history or more systematically by presenting a list of words and by testing free recall of them after a few minutes. The anatomical structures underlying episodic memory are the Papez circle (hippocampus, parahippocampus, ento- and perirhinal cortex, cingulate gyrus, fornix, nucleus anterior thalami, mamillothalamic tracts, and mammillary bodies), the basolateral limbic circuit (dorsomedial thalamic nucleus and amygdala), and the basal forebrain. Input from this system is necessary to ensure that the multimodal information from the environment which is processed and integrated in the neocortical association areas becomes memorable and retrievable.
A disorder of the system underlying episodic memory causes anterograde amnesia. The arterial blood supply of the anatomical structures subserving episodic memory has many sources, particularly the anterior cerebral artery and the anterior communicating artery (basal forebrain and fornix), posterior communicating artery (parts of the thalamus), posterior cerebral artery (hippocampus and parahippocampal gyrus), anterior choroidal artery (anterior hippocampus and adjacent cortex), and posterior choroidal artery (parts of the fornix).
There are three uncommon but relevant stroke syndromes which cause amnesia:
bilateral infarcts of the mediobasal temporal lobe
bilateral thalamic infarcts
subarachnoid hemorrhage from aneurysm of the anterior communicating artery.
Memory defects can follow unilateral or bilateral infarcts of the mediobasal temporal lobe, but are more common with left-sided and bilateral lesions. Recall of memories is mainly based on two processes, judgments that something is familiar and the conscious recollection of an episode with all attributes. Depending on the site of the lesion, recognition of familiarity or conscious recollection may be more disturbed. Furthermore, left-sided infarcts are known to cause predominantly verbal amnesia, whereas right-sided lesions may disturb visuospatial memories. Embolism from the heart or proximal vertebrobasilar artery is typically found to be the cause of bilateral infarcts.
Infarcts in the anterior and dorsomedial thalamus can produce severe memory deficits which are almost always accompanied by other neurological and neuropsychological symptoms such as attentional deficits, language disturbance, neglect, or executive dysfunctions. If amnesia is the leading clinical symptom TIA or stroke has to be distinguished from transient global amnesia (TGA). TIA and stroke are either accompanied by other neuropsychological symptoms or can be demonstrated with brain imaging.
Amnesia can be caused by temporal lobe or thalamic infarcts.
Reduced Vigilance or Coma as the Leading Symptom
Bilateral paramedian thalamic infarction can result from an occlusion of a single thalamic-subthalamic artery originating from the posterior cerebral artery (PCA). Patients can be hypersomnolent or comatose as if being in an anoxic or metabolic coma without localizable neurological signs. After regaining consciousness, disturbance of vertical gaze function (upgaze palsy, combined up- and downgaze palsy, or skew deviation) and neuropsychological deficits may become apparent.
Coma is more frequently found in patients with acute occlusion of the basilar artery in whom ischemia involves the bilateral pontine tegmentum. But here, additional neurological signs such as ophthalmoplegia and bilateral extensor plantar reflexes indicate brainstem ischemia.
Coma is frequently found in basilar artery occlusion.
Agitation and Delirium as the Presenting Symptom
According to the American Psychiatric Association (1987) delirium is defined as a clinical symptom with the following symptoms and signs:
reduced ability to maintain attention to external stimuli and to appropriately shift attention to new stimuli
disorganized thinking as indicated by irrelevant or incoherent speech
symptoms such as reduced level of consciousness, perceptual disturbances (misinterpretations, illusions, or hallucinations), disturbances of sleep–wake cycle, increased or decreased psychomotor activity, disorientation to time, place, or person, memory impairment
clinical features developing over a short time and tending to fluctuate over the course of a day
agitation and/or delirium may be the leading or the only symptom of acute stroke. It is uncommon and may not be considered a clinical manifestation of stroke. In a retrospective analysis, 19 of 661 stroke patients (3%) presented with delirium [13]. Right hemisphere infarcts that include the hippocampus, amygdala, entorhinal, and perirhinal cortex and the underlying white matter have been found to be most frequently associated with agitation and delirium.
Isolated Cranial Nerves
Stroke in the brainstem is typically indicated by (a) ipsilateral cranial nerve (III–XII) palsy (single or multiple) together with contralateral motor or sensory deficit, (b) bilateral motor and/or sensory deficits, or (c) disorders of conjugate eye movements. Rarely, cranial nerve palsy without any sensory or motor deficits may indicate a focal brainstem ischemia. Two out of 22 patients with focal ischemic lesions in the mesencephalon had an isolated palsy of the oculomotor nerve [14]. Thömke et al. [15] studied 29 patients with diabetes mellitus and oculomotor nerve palsy.
In five patients a focal ischemic lesion in the mesencephalon was causal for the deficit. Isolated palsy of the trochlear nerve has been described with focal hemorrhage or ischemia in the mesencephalon. Isolated palsy of the abducens, trigeminal, facial nerve, and even of the vestibular part of the vestibulocochlear nerve can be caused by focal hemorrhage or ischemia in the pons [16]. Ischemia may be caused by low flow in boundary zones.
Focal brainstem ischemia may cause isolated cranial nerve palsy.
Akinesia or Involuntary Movements
Acute hypokinetic or hyperkinetic movement disorders are an uncommon but sometimes the leading symptom of stroke.
Acute akinesia or hypokinesia of the contralateral part of the body is found after ischemic lesions of the medial part of the frontal lobe [17] (Figure 10.5). The supplementary motor area (SMA) is the medial part of the premotor cortex and is supplied by the anterior cerebral artery. It is part of a neuronal loop which involves frontal cortex, basal ganglia, and thalamus. The SMA receives excitatory input from the ventrolateral thalamus. Lesions of the SMA in the left hemisphere cause a lack of spontaneous speech (transcortical motor aphasia) with preserved comprehension and repetition and a hypokinesia/akinesia of contralateral body. Usually, these symptoms are transient. Lesions of the right SMA are associated with hypokinesia/akinesia of the left part of the body. Bilateral lesions of the mesial frontal cortex are known to cause severe akinetic states. Typically, there is a marked contrast between the paucity or absence of spontaneous movements and the preserved or even exaggerated ability to respond to external visual or tactile clues (“forced grasping”). Response to external stimuli helps to distinguish motor hypokinesia/akinesia from motor neglect. Motor (hemi)neglect may be an isolated symptom, but is mainly part of a more complex neglect syndrome which is characterized by a reduction of focal attention.
Figure 10.5 Contralateral akinesia/hypokinesia. A patient suffered from a large infarction in the territory of the right anterior cerebral artery (ACA). His left arm was spontaneously not used, but showed forced grasping reflexes to visual and tactile stimuli. The patient participated in an experiment with measurements of magnetic fields of the brain preceding spontaneous movements of the right index finger. With movements of the right finger an activation in the intact left supplementary motor area (SMA) preceding the onset of movement by more than 1 second was shown [17].
Hemichorea-hemiballism is the most frequently reported acute involuntary movement disorder in acute stroke. It has classically been described after an acute small deep infarct in the subthalamic nucleus [18].
Akinesia can be caused by lesions in the medial frontal lobe.
Focal Paresis
Weakness of one side of the body is the most frequent symptom of TIA or stroke. Typically either one part or several parts of the body are involved (face, arm, leg, face + arm, face + arm + leg). However, small strategic cortical infarcts can cause impairments of selective movements such as extension of fingers, hand, or foot, or movements of the tongue resembling peripheral nerve palsy (Figure 10.6).
Figure 10.6 Focal paresis. Diffusion-weighted MR images of ischemic lesions in the primary motor cortex mimicking clinically lesions of peripheral nerves. Top left – infarct with wrist drop imitating radial nerve palsy; top right – infarct with pseudo-ulnar nerve paresis; below – infarct with foot drop imitating peroneal nerve injury.
Uncommon Causes of Stroke and Associated Clinical Syndromes
Stroke Manifestations of Systemic Disease
Infective and Non-Infective Endocarditis: Multi-Territorial Pattern of Ischemic Stroke
Endocarditis of the heart and its valves can be classified into infective and non-infective types. The vast majority of endocarditis is secondary to infections caused by bacterial (Staphylococcus aureus, coagulase-negative Staphylococcus or Enterococcus) or, rarely, fungal (Candida, Aspergillus) organisms [19]. Cerebral embolism from infected valves is the central mechanism of neurological injury in patients with infective endocarditis. Embolic debris from infected valves typically lodges in the distal branches of the middle cerebral artery [20]. Over 50% of patients have infarcts involving more than one arterial territory [21]. Besides brain and retinal ischemia, other cerebrovascular complications include intracranial hemorrhage and subarachnoid hemorrhage [22]. Mycotic aneurysms are often assumed to be the cause of cerebral hemorrhage. They are thought to develop after septic microembolism to the vaso vasorum of cerebral vessels. But mycotic aneurysms are found in less than 3% of hemorrhages. More common mechanisms of hemorrhage include hemorrhagic transformation of the ischemic infarction, septic endarteritis and non-aneurysmal arterial erosion at the site of the previous embolic occlusion, septic coagulopathy, or concurrent anti-thrombotic medication use [23].
Non-infective endocarditis is termed non-bacterial thrombotic endocarditis (NBTE). It is characterized by the accumulation of sterile platelet and fibrin aggregates on the heart valves to form small vegetations. About 50% of NBTE cases occur in association with cancer, especially mucin-producing adenocarcinomas (particularly pancreatic carcinoma and non-small-cell lung cancer) and hematological malignancies (lymphoma and leukemia [24]). Although only less than 2% of patients with cancer have NBTE, up to 50% of these patients with NBTE suffer a stroke [25]. A significant proportion of patients with NBTE have other disorders, including rheumatic heart disease, rheumatological diseases such as lupus (where it is referred to as Lipman-Sacks endocarditis), AIDS, gastrointestinal diseases such as cirrhosis, and severe systemic illness, such as burns or sepsis [26]. Small and large multi-territorial infarction is a radiographic sign in NBTE [27]. Thus, encephalopathy rather than focal deficits may be the initial clinical presentation.
Endocarditis of various origins typically causes multi-territorial infarctions.
Inflammatory Vasculopathies and Connective Tissue Disease: A Chronic and Multisystemic Disease
Inflammatory vasculopathies and connective tissue disease are Takayesu’s arteritis, systemic lupus erythematosus (SLE), anti-phospholipid antibody syndrome, Sneddon syndrome, primary systemic vasculitis (classic polyarteritis nodosa, microscopic polyangiitis, Churg-Strauss syndrome, Wegener’s granulomatosis), Sjögren syndrome, Behçet disease, primary angiitis of the central nervous system, and paraneoplastic vasculitis.
Warlow et al. [1] have summarized clinical clues which may in general indicate inflammatory vasculopathies and connective tissue disease. Patients may present with TIA and stroke, but also with encephalopathy:
preceding or accompanying systemic features such as weight loss, headache, malaise, skin rash, livedo reticularis, arthropathy, renal failure, and fever
lack of any other obvious or more common cause of stroke
younger patient in most cases (an exception being giant cell arteritis)
a raised ESR and C-reactive protein
anemia and leukocytosis in the routine blood screening tests
when there is diagnostic suspicion, specified immunological tests such as raised serum anti-phospholipid, double-stranded DNA, or anti-neutrophil cytoplasmic antibodies (ANCAs).
Among those diseases, giant cell arteritis and systemic lupus erythematosus are uncommon but not rare and will be presented in more detail.
Giant cell arteritis is also known as temporal arteritis, cranial arteritis, or Horton’s disease. The annual incidence increases with age from 2.6/100 000 for those aged between 50 and 59 years to 44.6/100 000 for those older than 80 years. Headache, especially in the night, located in the temporal region, fever, weight loss, fatigue, and malaise or arthralgia and jaw claudication are the predominating symptoms. Most patients with giant cell arteritis have symptoms of polymyalgia rheumatica, which may precede the headache. A raised ESR (over 50 or even 100 mm in the first hour) is also indicative.
Ischemic symptoms of the retina and the brain usually develop late in the course of disease. But stroke may even be the first indication of disease. Giant cell arteritis involves the ophthalmic, posterior ciliary, and central retinal arteries, which causes infarction of the optic nerve. It may also involve intracranial vessels, particularly the extradural vertebral arteries, which may cause stroke. Diplopia and ophthalmoplegia may develop, but are mainly caused by necrosis of the extraocular muscles and not by brainstem ischemia.
Systemic lupus erythematosus is a chronic autoimmune disease affecting mainly young women. It more often causes a generalized subacute or chronic encephalopathy than focal ischemic or hemorrhagic cerebral episodes. Intimal proliferation involving small vessels may represent florid or healed vasculitic lesions. Large artery occlusions can be explained in some patients by cardiac sources (NBTE: non-bacterial thrombotic embolism). Most patients have circulating anti-nuclear antibodies. A raised anti-nuclear factor is highly sensitive, but not specific. Double-stranded DNA and anti-Sm antibodies are much more specific, but are found in less than half of cases. A high proportion of patients also have anti-phospholipid antibodies, which seem to be particularly associated with cardiac valvular vegetations and arterial thrombosis. The anti-phospholipid syndrome cannot be diagnosed on the basis of a raised single titer of antibody in the serum alone. The titer must be substantially raised on several occasions and must be associated not only with ischemic stroke, but also with other manifestations of disease such as deep venous thrombosis, recurrent miscarriages, livedo reticularis, cardiac valvular vegetations, migraine-like headache, thrombocytopenia, or hemolytic anemia.
Inflammatory vasculopathies require special diagnostic tests.
Related posts:
Chapter 4 – Imaging for Prediction of Functional Outcome and for Assessment of Recovery
Chapter 8 – Cardiac Diseases Relevant to Stroke
Chapter 16 – Stroke and Dementia
Chapter 19 – Acute Therapies for Stroke
Chapter 22 – Management of Acute Ischemic Stroke and its Late Complications
Chapter 21 – Intensive Care of Stroke
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