♦ Most dissections affect the extracranial portions of the internal carotid and vertebral arteries (Figures 8-1 and 8-2). Carotid dissections most often occur 1.5 to 2 cm above the carotid bifurcation (different from atherosclerosis, which characteristically affects the carotid bulb) and usually end at the skull base, before the artery penetrates the petrous bone. Vertebral artery dissections typically affect the V3 segment, originating at the C1–C2 level as the artery leaves the transverse foramen of the axis and makes its turn to enter the intracranial compartment.^2,¹⁰

♦ Dissections may affect multiple cervical vessels simultaneously in 15% of cases.

♦ MRI and MRA of the neck are the best imaging modalities for the diagnosis of cervical artery dissections (Figure 8-3).¹¹^–¹⁴

♦ CT angiograms are also useful for the noninvasive detection of arterial dissections (Figure 8-4), particularly in the emergency setting.

♦ The angiographic signs of cervical artery dissections are listed in Table 8-1. These changes can be seen on MRA, CT angiography (CTA), or catheter digital subtraction angiography.

♦ Angiography of the intracranial vessels allows identification of dissections extending into the intracranial compartment and intracranial pseudo-aneurysms (see Figure 8-2). Some consider the presence of these findings a relative contraindication for anticoagulation (used by many practitioners to prevent embolic infarctions after dissections, although never formally studied for this particular indication). However, subarachnoid hemorrhage typically occurs at the time of formation of dissecting aneurysms. The risk of this complication subsequently appears to be very low.¹⁵

♦ MRI of the neck should include thin cuts of fat-suppressed T1-weighted sequence to allow the identification of the intramural hematoma (see Figure 8-3). It appears as a hyperintense signal, which may be eccentric (as a crescent) or concentric (as a doughnut), and widens the external diameter of the vessel. This sequence may also permit visualization of an intimal flap (generally seen as a thin, curvilinear, hypointense signal change between the true and a false lumen). Flow void may be normal, narrowed (eccentrically or concentrically), or absent. However, loss of flow void in these cases does not necessarily represent vessel occlusion, because very slow flow may cause signal loss in a patent vessel.

♦ There is some evidence that concentric intramural hematomas may be associated with higher risk of brain ischemia, whereas eccentric intramural hematomas might tend to cause more nonischemic clinical signs (such as Horner’s syndrome).¹⁶

♦ Catheter digital subtraction angiography may occasionally demonstrate signs of dissection (particularly small intimal flaps) in patients with no definite abnormalities on MRI/MRA of the neck. Thus it may be reasonable to perform catheter angiography in selected cases when the clinical suspicion of dissection is high but the diagnosis could not be confirmed by noninvasive modalities. In these situations, the yield of catheter angiography may be higher for vertebral artery dissections.¹³

♦ Ultrasound may be useful for the diagnosis and monitoring of extracranial carotid artery dissection. It is reliable to demonstrate the narrowing or occlusion of the vessel lumen (except when its location is too high). Intramural thrombus and intimal flap may occasionally be recognized by their increased echogenicity (but the sensitivity of ultrasound to detect these abnormalities is low).^17,¹⁸ When stenosis or occlusion was seen on ultrasound upon presentation, this simple test can be used for subsequent monitoring.

♦ The most common pattern of ischemia in patients with carotid artery dissection is that of multiple acute brain infarctions (suggestive of embolism), often involving cortical and watershed areas.¹⁹

♦ In cases of vertebral artery dissection the pattern of acute multiple brain infarctions also predominates (Figure 8-5), affecting the terminal branches of the basilar artery. More than a third of patients present signs of ischemia in the cerebellar border-zone distribution. Pontine ischemia is less common after vertebral artery dissections than with atherosclerosis of this vessel, and isolated small thalamic infarctions appear to be distinctly uncommon with both mechanisms of large-vessel vertebrobasilar disease.²⁰

♦ In cases of arterial occlusion, recanalization is possible within the first few weeks, and it may be more common in the vertebral arteries.²¹ Thus, follow-up imaging is indicated in these patients. We typically recommend repeating imaging of the neck 8 to 12 weeks after a documented dissection with compromise of the vessel lumen.

♦ Cervical aneurysms formed as a consequence of arterial dissections tend to be persistent, but their prognosis is benign.²²^–²⁴

♦ Intracranial dissections are uncommon. Most commonly affected locations are the V4 segment of the vertebral artery and the supraclinoid carotid artery. Middle cerebral and basilar artery dissections are exceptional. Intracranial dissections may present with subarachnoid hemorrhage, which is not infrequently fatal.

♦ Recurrence of dissections are possible, but the risk is low,²⁵^–²⁷ particularly after the first two months.^28,²⁹

Figure 8-2 Illustrations of various cases of arterial dissection involving the carotid (A–C) and vertebral arteries (D–F) as depicted by conventional angiography. (A) Luminal tapering and string sign (arrow). (B) Luminal tapering and occlusion (arrow). (C) Luminal tapering and string sign followed by functional occlusion (arrow). (D) Vertebral artery dissection with pseudo-aneurysm (arrowhead), small intimal flap (open arrow) and double lumen (solid arrow). (E and F) Additional examples of vertebral artery pseudo-aneurysms after dissections (arrows).

Figure 8-3 Examples of arterial dissection diagnosed by magnetic resonance imaging and angiography. (A) Cervical left internal carotid artery tapering and occlusion due to dissection. (B) Axial T1-weighted sequence with fat saturation of the same patient showing a hyperintense crescent sign caused by an eccentric intramural thrombus (arrow). (C) Another example of intramural thrombus seen on fat saturated, T1-weighted axial cuts. (D) Magnified picture of the same finding (arrow).

Figure 8-4 Diagnosis of arterial dissection by computed tomography angiography (CTA). (A) Computed tomography scan showing a hyperdense left middle cerebral artery sign (arrow). (B) Diffusion-weighted imaging sequence of magnetic resonance imaging showing an area of bright signal on the left striatocapsular region. (C) Apparent diffusion coefficient showing low signal in the same region, thus confirming restricted diffusion from acute infarction. (D) Source images of the CTA showing lack of contrast flow in most of the lumen of the left carotid artery, with a residual eccentric segment of patent lumen (arrow). (E) Three-dimensional reconstruction of the CTA depicting the left carotid dissection causing tapering and occlusion of the lumen (arrow). (F) Isolated CTA of the left carotid artery clearly demonstrating the flamelike dissection and occlusion of the vessel (arrow).

TABLE 8-1 Angiographic signs of cervical artery dissections.

Tapered luminal narrowing (string sign)

With stenosis

With occlusion

Pseudo-aneurysm (segmental dilatations)

Oval segmental dilatation of the lumen

Extraluminal pouch

Small dilatation at the end of a string sign

Intimal flap^*

Double lumen

High carotid stenosis or occlusion

* Usually only seen on catheter angiography but sometimes noted on thin axial cuts of magnetic resonance imaging scans.

Figure 8-5 A 35-year-old woman with chronic headaches and neck pain following an automobile accident presented to the emergency department with acute right-sided neck pain, dizziness, dysarthria, and dysphagia. Her neck had been manipulated by a chiropractor the day before. Magnetic resonance imaging showed acute areas of ischemia in the right cerebellar hemisphere, scattered across the territories of the posterior-inferior and anterior-inferior cerebellar arteries (diffusion-weighted imaging sequence [A and B], infarctions signaled by arrows). Magnetic resonance angiography with gadolinium revealed right vertebral artery occlusion in its V3 segment from a dissection (C, arrow). Notice that the distal portion of the V4 segment is filled from retrograde flow. The patient recovered well despite persistent vessel occlusion on repeat imaging 4 months later.

AORTIC DISSECTIONS

♦ Aortic arch dissection may cause ischemic brain infarctions by generating emboli or, most commonly, affecting the cervical arteries. However, this complication is uncommon.

♦ Aortic dissection must be suspected in patients presenting with stroke who complain of severe chest pain radiating to the back or the neck. These patients may be hemodynamically unstable. However, painless aortic dissections in patients presenting with cerebral ischemia may go initially unrecognized; asymmetric pulses or aortic murmur may be useful clues in these instances.³⁰

♦ The diagnosis of thoracic aortic dissection can be reliably established by noninvasive angiography (MRA or CTA) (Figure 8-6) and even by ultrasound (Figure 8-7).

♦ The stroke pattern varies according to the mechanism of infarction. Aortic embolism may result in bilateral infarctions (Figures 8-6 and 8-7) and may involve anterior and posterior circulation territories. Extension of dissection may also provoke brain ischemia from artery-to-artery-embolism, but in this case the infarctions will be confined to the territory of the affected cervical vessel. If the dissection causes severe narrowing or occlusion of the cervical vessels, hemodynamic infarctions in watershed distributions may occur.

Figure 8-6 A 65-year-old hypertensive man presented to the emergency department with complaints of severe chest pain radiating to the back. On examination, he was confused and dysarthric. He had mild left hemiparesis. Aortic dissection was suspected on chest X-ray and confirmed by noninvasive angiography. (A) Diffusion-weighted sequence of brain magnetic resonance imaging revealed bilateral scattered areas of acute ischemia predominantly (but not exclusively) located in the external watershed distributions of both cerebral hemispheres; the pattern was considered most consistent with an embolic shower from a proximal source. (B) Magnetic resonance angiography (MRA) of the aortic arch revealed a large aortic aneurysm with preservation of the cervical branches. (C) Another view of the MRA of the chest showing the double lumen at the level of the aortic arch and descending thoracic aorta (arrow). (D) Axial cut of the computed tomography scan allows clear visualization of the aortic double lumen (arrow). (E) MRA of the abdominal aorta disclosing extension of the dissection and double lumen into the left iliac artery. (F) Axial image of the MRA at the level of the upper renal poles.

Figure 8-7 Another example of stroke caused by aortic dissection. Notice bilateral strokes on fluid-attenuated inversion recovery (A) with a right posterior frontal infarction of embolic appearance (arrow) and small areas of ischemia in the internal watershed of both hemispheres (arrowheads). The aortic arch aneurysm was diagnosed by magnetic resonance angiography (B). Ultrasound clearly showed the presence of a double lumen (C and D, arrows).

FIBROMUSCULAR DYSPLASIA

♦ Fibromuscular dysplasia (FMD) is a systemic arteriopathy involving the craniocervical, splanchnic, and renal vessels. Pathological findings consist of rings of fibrous tissue (from dysplastic smooth muscle) in the tunica media alternating with areas of medial thickening and disrupted elastic lamina. As a result, the lumen has narrower and wider areas along the affected segments, leading to the characteristic angiographic appearance of a “string of beads” (Figure 8-8).

♦ FMD predominantly affects the distal extracranial segments of the vertebral and carotid arteries. Intracranial involvement is observed less frequently (Figure 8-8, D), mostly in the petrous and cavernous segments of the internal carotid arteries.

♦ The diagnosis may be suspected on Duplex ultrasound but is confirmed by angiography. Although the string-of-beads pattern represents the hallmark of the condition, other presenting features may include relatively long areas of tubular stenosis, diverticular dilatations, or fusiform aneurysmatic formations.³¹

♦ Spontaneous dissections are more common in these patients, and this mechanism constitutes the most solidly proven association with an increased risk of stroke.^6,³² Recurrent dissections may occur more commonly in patients with FMD.³³

♦ Catheterization of affected vessels should be performed cautiously and only when indispensable because the risk of iatrogenic dissection is elevated in these cases.

Figure 8-8 Illustrations of fibromuscular dysplasia on conventional angiography. Notice the string-of-beads appearance across long segments of cervical carotid and vertebral arteries (A–C, arrows). (D) A case of intracranial involvement with associated stenosis of the M1 segment of the right middle cerebral artery (arrow).

DOLICHOECTASIA

♦ Arterial dolichoectasia, a dilatative angiopathy with predilection for intracranial vessels, may affect the carotid and vertebrobasilar systems. Its etiology is unclear, but it has been reported to be associated with traditional vascular risk factors (older age, male sex, hypertension, and history of myocardial infarction), although not with carotid atherosclerosis.³⁴ Intracranial artery dolichoectasia is also associated with enlargement of the descending thoracic aorta, suggesting that the vasculopathy is not restricted to intracranial vessels.³⁵

♦ It can produce symptoms from compression of adjacent structures, ischemia (typically in distributions of penetrating arteries or, in the case of vertebrobasilar dolichoectasia [Figure 8-9] in the territory of the posterior cerebral arteries), or rupture with intraparenchymal or subarachnoid hemorrhage.³⁶^–⁴⁰ It has also been associated with increased incidence of pathologically proved small vessel disease.⁴¹ Risk of recurrent ischemic infarctions is elevated.⁴⁰

♦ The diagnosis can be surmised from the dilatated and elongated flow voids on CT and MRI of the brain, but it is confirmed by noninvasive angiographic studies. Conventional angiography is rarely necessary except in cases of hemorrhage.

Figure 8-9 A 69-year-old man who consulted for progressive symptoms of brainstem dysfunction. (A) Nonenhanced head computed tomography scan showed marked dilatation of the vertebrobasilar system with calcification of the vessel walls (arrow). (B) Magnetic resonance angiography confirmed the diagnosis of vertebrobasilar dolichoectasia with an associated thrombosed fusiform aneurysm arising from the left vertebrobasilar junction (arrow). (C) Sagittal T1-weighted sequence shows the brainstem compression by the thrombosed aneurysmatic formation (arrow). (D) Axial T2-weighted sequence provides a different view of the compressive vessel dilatation (arrow). (E) Magnified view of the magnetic resonance angiography of the vertebrobasilar system; notice elongation and dilatation of the vessels and faint visualization of the fusiform aneurysm (arrow).

MOYAMOYA

♦ The term “moyamoya” (which translates from Japanese as “hazy puff of smoke”) identifies an angiographic pattern of collateralization that occurs following progressive, severe narrowing (often culminating in occlusion) of the supraclinoid segments of the internal carotid arteries and proximal branches of the circle of Willis (Figure 8-10).

♦ Moyamoya disease is a nonatherosclerotic, noninflammatory vasculopathy that occurs predominantly in patients of Japanese ancestry,^42,⁴³ in whom it was initially described. However, it may also affect other ethnic groups.⁴⁴^–⁴⁹ The etiopathogenesis of moyamoya disease is unknown; occurrence of familial cases argues for a genetic contribution.

♦ Japanese cases present in childhood with ischemic infarctions and in adulthood with brain hemorrhages. In Occidental patients, ischemia predominates and, although the natural history of the condition may be more benign than in Asian cases,⁴⁴ the risk of recurrent ischemic strokes is high.⁴⁷

♦ Angiographic findings of moyamoya can also be seen in patients with advanced intracranial atherosclerosis, radiation-induced vasculopathy, sickle cell disease, meningitis, systemic vasculitis, and cocaine use.⁵⁰^–⁵³ Although these cases may be classified as moyamoya syndrome or moyamoya phenomenon, they should not be confused with cases of moyamoya disease.

♦ The diagnosis is made angiographically. However, brain imaging may suggest the diagnosis by disclosing multiple flow voids in the basal ganglia on CT scan or T1-weighted sequence, appearing as dots that enhance after contrast is administered. Sulci appear bright on FLAIR because of engorgement of pial vessels. Areas of ischemic infarction may be multiple and typically distributed in deep or watershed regions. DWI is helpful in distinguishing acute versus chronic lesions. Hemorrhages tend to be ganglionic or intraventricular (Figure 8-10).

♦ Although the diagnosis can be established with noninvasive angiograms, performing catheter digital substraction angiography is advisable to define the extent of the disease with certainty. It allows optimal visualization of the areas of arterial narrowing/ occlusion and the collateral arborization (deep lenticulostriate and thalamoperforator vessels, which appear earlier and produce the moyamoya pattern, and transdural connections between external and internal carotid artery branches, which develop later). Digital substraction angiography is indispensable for preoperative planning when surgery is contemplated. It may also disclose the presence of intracranial aneurysms because patients with moyamoya have a higher incidence of these vascular anomalies (in fact, lenticulostriate artery aneurysms can be seen in these patients).⁵⁴

Figure 8-10 A 22-year-old woman without history of hypertension who presented with massive intraventricular hemorrhage and left basal ganglia hematoma on computed tomography scan (A). Digital substraction angiography revealed occlusion of the supraclinoid left internal carotid artery with the typical moyamoya pattern of collateralization (arrows) (B and C).

CADASIL

♦ Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominant disorder caused by a mutation in the NOTCH3 gene. It is characterized by migraines, recurrent strokes, psychiatric symptoms, and rapidly progressive dementia.⁵⁵ The disease process affects primarily the vascular smooth muscle cells with predilection for the arterioles of the brain.

♦ Although the diagnosis requires genetic confirmation, brain imaging is extremely valuable to evaluate this diagnosis. Brain MRI shows multiple subcortical infarctions with diffuse leukoencephalopathy (Figure 8-11), findings that progress over time. Predominant involvement of the anterior temporal lobes is characteristic, although lesions are also common in the frontal-parietal white matter and external capsule.⁵⁶^–⁵⁸ Lesions tend to become confluent over time, particularly in the temporal poles.⁵⁷

♦ Intracerebral hemorrhages can also occur, although they are very infrequent.⁵⁹ Microhemorrhages on T2^*/GRE sequence are probably more common, especially when patients are also hypertensive and diabetic.⁶⁰

♦ Electron microscopy examination of skin biopsy specimens searching for extracellular granular osmiophilic material in the tunica media of small blood vessels may also be useful to screen for this disorder.⁶¹

Figure 8-11 Various examples of patients with different stages of CADASIL seen on fluid-attenuated inversion recovery sequence of magnetic resonance imaging. (A) More scattered distribution of lesions in a less advanced case. (B) Early predominance of involvement of the anterior temporal lobes. (C) Confluent white matter lesions in a more advanced case. (D) Extensive temporal involvement late in the disease.

MELAS

♦ Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS) is an inherited mitochondrial DNA disorder that manifests with cortical lesions resembling infarctions. However, these lesions extend across vascular territories and exhibit migration over time (they resolve and then recur in the same or different location).⁶²

♦ Lesions are more common in the parieto-occipital regions (including cortex normally perfused by the middle and posterior cerebral arteries) but may involve the temporal lobes and basal ganglia (Figure 8-12, A and B). They are most often multiple, and their size is variable.

♦ Initially they show an inflammatory appearance with gyriform swelling and compression of sulci. Subcortical white matter may be involved or spared. On MRI, these acute lesions are bright on DWI (Figure 8-12, C) but often normal on apparent diffusion coefficient (ADC; distinguishing them from true infarctions),⁶³ hyperintense on T2-weighted imaging and FLAIR, and frequently enhance with contrast. GRE rarely shows evidence of microhemorrhage.⁶⁴

♦ Angiograms prove absence of arterial narrowing or occlusions and may suggest luxury perfusion. Indeed, perfusion scans confirm the presence of hyperperfusion in the areas of acute involvement.⁶⁵

♦ As lesions evolve, signs of laminar necrosis may be seen. In the chronic stage, neuroimaging may demonstrate cortical atrophy, atrophy of deep gray nuclei, and multifocal hyperintensities on T2 and FLAIR sequences in the deep white matter and basal ganglia.

♦ Multivoxel MR spectroscopy (MRS) is enormously valuable to substantiate the diagnosis of MELAS. Acute lesions have a characteristic lactate “doublet” peak resonating at 1.3 ppm when spectra is acquired with short echo time (TE; 35 msec; Figure 8-12, E) and inversion of the lactate peak when a long TE (136–144 msec) is used.⁶⁶ MRS abnormalities may precede changes on DWI.⁶⁷

♦ Neuronal hyperexcitability (often associated with local epileptiform discharges) has been proposed as the underlying mechanism exacerbating energy failure and inducing inflammatory changes and local acidosis followed by neuronal death in the acute brain lesions of patients with MELAS.^68,⁶⁹

Figure 8-12 Illustrations of diagnostic imaging features of MELAS. (A and B) Typical lesions of MELAS in the parietal, occipital, and temporal cortex on fluid-attenuated inversion recovery (FLAIR) sequence of magnetic resonance imaging (arrows). (C) Another case of MELAS with bright cortical areas on diffusion-weighted imaging (arrows) that corresponded to a normal signal on apparent diffusion coefficient; notice absence of signal abnormalities on FLAIR (D). (E and F) A third patient with diagnosis of MELAS exemplifying the characteristic finding lactate doublet peak on MRS (arrows) despite normal FLAIR appearance.

REVERSIBLE CEREBRAL VASOCONSTRICTION

♦ This form of angiopathy, often referred to as Call-Fleming syndrome,⁷⁰ is caused by transient, reversible vasoconstriction of the arteries of the circle of Willis and their branches.⁷¹

♦ It is most commonly encountered in women during early puerperium, but a similar disorder may be observed in late pregnancy.

♦ Additional causes of reversible cerebral vasoconstriction include migraine, subarachnoid hemorrhage, drugs (ergot derivatives; sympathomimetics such as decongestants, appetite suppressants, cocaine, and amphetamines; serotoninergic agents such as triptans), and, rarely, carotid endarterectomy.⁷¹

♦ However, not all of these conditions may produce vasospasm by the same mechanism; it is very likely that the pathophysiology of cerebral vasospasm after aneurysmal subarachnoid hemorrhage differs substantially from the vasoconstriction seen in postpartum or with migraines.

♦ Brain imaging typically demonstrates small, multifocal areas of infarction in the posterior head regions or watershed distributions (Figure 8-13, A and B). Sparing of the calcarine cortex and medial occipital lobes differentiates these infarctions from those produced by embolism.⁷² Perfusion scans may reveal large areas of hypoperfusion. Serial brain imaging may show additional areas of ischemia before the vasculopathy subsides.

♦ Angiography indicates the diagnosis by disclosing multifocal areas of arterial narrowing and dilatation during the acute phase (Figure 8-13, C and D) with subsequent resolution (over days or weeks). Large and medium-sized arteries are most often affected. Noninvasive angiographic studies (MRA, CTA) may be useful, but conventional catheter angiography remains the best method to certify the diagnosis. Transcranial Doppler may be used to monitor disease progression.

Figure 8-13 A 32-year-old woman who developed severe headache and confusion 2 weeks after delivering her second child. Magnetic resonance imaging showed acute ischemia in the internal watershed distribution of both cerebral hemispheres, as shown on diffusion-weighted imaging (A) and apparent diffusion coefficient (B) (arrows). Magnetic resonance angiography disclosed severe vasospasm on both supraclinoid internal carotid arteries and M1, M2, A1, and A2 segments (arrows) (C). Digital substraction angiography confirmed the diagnosis of severe vasospasm (arrows); right carotid injection shown (D). Symptoms resolved within days and follow-up angiography 2 weeks later was normal.

HYPERCOAGULABILITY

♦ In general, strokes related to thrombophilia do not have a distinctive radiological pattern. In patients with hypercoagulable conditions, brain infarctions may be due to arterial occlusions (mostly embolic, but thrombosis in situ is also possible) (Figure 8-14) or venous thrombosis. Lesions are often multiple or recurrent and tend not to be restricted to a single vascular territory.

♦ Thrombotic thrombocytopenic purpura (TTP) is a hematological disorder with multisystemic manifestations that include fever, thrombocytopenia, cutaneous purpura, microangiopathic hemolytic anemia (with formation of schistocytes in the peripheral blood), neurological symptoms, and renal dysfunction. Patients may have headaches, confusion, depressed level of consciousness, seizures, and focal deficits with or without brain infarctions or hemorrhage.

♦ TTP may cause strokes by inducing thrombosis or vascular and rheological changes with flow restriction. Thrombosis may cause small subcortical or cortical infarcts (Figure 8-15),⁷³ territorial infarctions, or even massive strokes.⁷⁴ Compromised perfusion due to intravascular hemolysis and arterial narrowing (which has been documented to be reversible)⁷⁵ produces watershed infarctions.

♦ Apart from brain infarctions, patients with TTP can have reversible radiological changes, often consistent with the pattern of reversible posterior encephalopathy syndrome in patients with severe hypertension and renal failure.⁷⁶ Extensive brainstem involvement is possible in these cases.⁷⁷

♦ Reversibility of radiological brain lesions is associated with better prognosis for recovery,⁷⁸ although small persistent lesions may be seen in patients who recover well.⁷⁹

Figure 8-14 A 42-year-old man with a past medical history remarkable only for an unprovoked deep venous thrombosis in the right leg 2 years earlier presented to the emergency department after an episode of transient left-sided weakness. Examination revealed a left visual field deficit to confrontation. (A) Magnetic resonance imaging showed a right parieto-occipital acute infarction in the middle and posterior cerebral arteries watershed territory (arrow). Magnetic resonance angiography disclosed an occlusion of the right supraclinoid internal carotid artery. Comprehensive stroke workup revealed high titers of anticardiolipin antibodies (immunoglobulins M and IG). Patent foramen ovale was excluded by transesophageal echocardiogram and transcranial Doppler with injection of agitated saline.

Figure 8-15 Example of multifocal stroke in a patient with thrombotic thrombocytopenic purpura. (A) Fluid-attenuated inversion recovery sequence of magnetic resonance imaging showing bilateral subcortical and left parasagittal cortical strokes (arrows). (B) Peripheral smear revealing the characteristic schistocytes (arrow).

VASCULITIS

♦ Cerebral vasculitis may result from multiple causes. Main categories are primary, autoimmune reactions, infections, and radiation (Table 8-2).

♦ Patients with vasculitis may present with ischemic or hemorrhagic strokes but most often have preceding headaches, personality changes, alterations in level and content of consciousness, and signs of meningeal inflammation or increased intracranial pressure.

♦ Angiograms are the most helpful imaging modality in patients with suspected vasculitis. The distinctive imaging feature of vasculitis cases as a group is the visualization of multifocal areas of segmental luminal narrowing and dilatation (vascular beading). The type, size, and location of the blood vessels involved vary with each specific entity.

♦ Brain imaging may show cortical and subcortical ischemic lesions of different sizes and often distributed across different vascular territories.

♦ CT scan is relatively insensitive to detect ischemic changes related to vasculitis, but it may show multifocal areas of decreased attenuation in patients with multiple larger infarctions. Its value is much greater in cases with hemorrhage. Contrast enhancement may be seen in some lesions (or the leptomeninges in cases associated with meningitis) after iodine administration.

♦ MRI can demonstrate the parenchymal lesions in greater detail. DWI allows discrimination of acute lesions. T2^* GRE may show microhemorrhages. Gadolinium-T1 sequence can reveal patchy areas of enhancement.

TABLE 8-2 Differential diagnosis of cerebral vasculitis.

Primary central nervous system angiitis

Susac’s syndrome

Cogan’s syndrome

Eale’s disease

Systemic noninfectious vasculitis

Giant cell arteritis

Takayasu arteritis

Systemic lupus erythematosus

Polyarteritis nodosa

Microscopic polyangiitis

Wegener’s disease

Churg-Strauss’ disease

Sarcoidosis

Beçhet’s disease

Infectious vasculitis

Bacterial (tuberculosis, bacterial meningitis, syphilis)

Viral (VZV, CMV, HIV,^* etc.)

Fungal (cryptococosis, aspergillosis, mucormycosis, candidiasis etc.)

Parasitic (cysticercosis)

Radiation

Drugs of abuse (cocaine, amphetamines)^†

Tumors and proliferative disorders^‡

Infiltrating angiocentric lymphoma

Lymphomatoid granulomatosis

CMV, cytomegalovirus; HIV, human immunodeficiency virus, VZV, varicella zoster virus.

* Most cases are related to a small vessel vasculopathy, which does not include major perivascular or intravascular inflammatory infiltrates (hence, not strictly a vasculitis).⁸⁰

† Many of these cases may be caused by acute, severe vasoconstriction.

‡ Questionable if this truly can be considered within the category of vasculitis.

Primary Central Nervous System Angiitis

Case Vignette

A 53-year-old man with history of biopsy-proved primary central nervous system (CNS) angiitis was transferred from another hospital because of recurrent strokelike episodes. His neurological symptoms had started 3 years earlier when he developed severe headaches and some degree of confusion. MRI of the brain showed scattered subcortical lesions, and his cerebrospinal fluid had inflammatory features (125 cells/mm³ with lymphocytic predominance and normal cell morphology, protein level of 112 mg/dl with normal) glucose content. Double substraction angiography (DSA) revealed multifocal irregularities in large and smaller intracranial arteries. Brain biopsy confirmed the diagnosis of CNS vasculitis. Extensive workup for infection, tumor, and systemic vasculitis was negative. The patient was treated with intravenous corticosteroids with good clinical response. He remained asymptomatic on prednisone until 2.5 months before the current hospitalization when he developed acute dysarthria and left hemiparesis. Brain imaging disclosed a new right subcortical stroke, and noninvasive angiography showed increased signs of vasculitis. The dose of prednisone was increased, but the patient continued to worsen. His attention span declined, and he became more irritable. Over the following 3 months, he had two more episodes of increased dysarthria and incoordination. A third event prompted the hospitalization. MRI of the brain at that time showed a new area of acute ischemia in the right corona radiata (Figure 8-16, A and B). DSA displayed extensive arterial beading in all major intracranial arteries (Figure 8-16, C and D). Despite high-dose intravenous steroids, the patient’s level of alertness worsened over the subsequent week. On the seventh hospital day, he was found stuporous and required intubation for airway protection. He appeared to have a new right hemiparesis. Repeat MRI of the brain showed enlargement of the area of ischemia on the right hemisphere and a new, larger ischemic infarction on the left hemisphere (Figure 8-16, E and F). He was treated with a pulse dose of cyclophosphamide without response. Plasma exchange was also tried unsuccessfully. He became comatose, and after failure to improve over the following 10 days, his family requested withdrawal of life support.

Figure 8-16 (A) Diffusion-weighted imaging (DWI) sequence of magnetic resonance imaging (MRI) showing an area of acute ischemia in the right corona radiata. (B) Fluid-attenuated inversion recovery (FLAIR) sequence of MRI revealing the acute right hemispheric stroke but also disclosing previous areas of contralateral infarction. (C) Digital substraction angiography (DSA), right carotid injection, illustrating the extensive vasculitic changes (arrows). (D) Magnified view of the same DSA allowing better visualization of the vascular irregularities (arrows). (E) Repeat DWI after major clinical decline showing extension of the area of right hemispheric ischemia with a new, large infarction on the left hemisphere. (F) Repeat FLAIR displaying the extensive bilateral infarctions.

♦ Primary or isolated CNS angiitis is a rare form of vasculitis that exclusively affects small and middle-sized arteries and veins of the brain, spinal cord, and leptomeninges. Pathological examination most often demonstrates nonspecific mononuclear infiltration of vessel walls associated with variable degrees of granulomatous formation and necrosis.

♦ Cases with predominant involvement of small vessels present with severe headaches and encephalopathy. Primary CNS angiitis mainly affecting medium-sized vessels is more likely to present with stroke.⁸¹

♦ Brain imaging features are highly variable. Multiple small cortical and subcortical infarctions, often with contrast enhancement, are most characteristic and suggest small vessel inflammation.^82,⁸³ Similar lesions may be seen in the spinal cord.^82,⁸⁴ Territorial infarctions indicate medium-sized vessel disease.⁸¹ Even benign cases often have abnormalities on brain MRI at presentation.⁸⁵ Intracranial hemorrhages are uncommon.

♦ Digital substraction angiography indicates the diagnosis by showing multifocal stenoses and dilatations (beading or sausage-like appearance) with possible areas of occlusions (Figures 8-16 and 8-17).⁸⁶

♦ Angiograms can be negative in patients with biopsy-proved primary CNS angiitis.⁸⁶ Conversely, typical angiographic abnormalities may be seen in patients with negative biopsies and proved alternative diagnosis.⁸⁷

♦ Brain and leptomeningeal biopsy establishes the diagnosis of primary CNS angiitis with certainty when it demonstrates signs of vascular inflammation or necrosis. However, biopsy can be negative in some cases with typical angiographic findings and clear response to immunosuppressants.⁸³ Obtaining the biopsy specimen from abnormal areas on MRI increases the yield of the pathological examination.⁸³

♦ Findings on brain and vascular imaging have prognostic implications. Outcome is worse in patients with cerebral infarctions and large vessel involvement.⁸³ Conversely, patients with prominent gadolinium-enhanced brain lesions or marked meningeal enhancement have better prognosis.^83,⁸⁸ The histological pattern of positive biopsy specimens (granulomatous, lymphocytic, or necrotizing) does not appear to determine prognosis.⁸³ However, patients with suspected CNS angiitis but negative biopsy may have a relatively favorable outcome regardless of whether immunosuppressants are used.⁸⁹

♦ A benign form of primary CNS angiitis has been reported (benign angiopathy of the nervous system)⁸⁵ characterized by striking angiographic findings but prompt reversibility with less intensive immunosuppression; however, it remains unclear whether this condition truly represents a benign variant of primary CNS angiitis or is rather a different entity altogether (e.g., some of these cases might be a form of reversible cerebral vasoconstriction syndrome) (Figure 8-18).

Figure 8-17 Additional examples of primary central nervous system vasculitis on cerebral angiography. Notice multifocal areas of arterial beading, some indicated by small arrows.

Figure 8-18 A 52-year-old woman presented for evaluation of thunderclap headache. Initial computed tomography (CT) scan performed at a local center was reportedly negative, and the patient was prescribed sumatriptan. The headache continued, and she became slightly confused before consulting us for a second opinion. Repeat CT scan of the brain revealed subarachnoid hemorrhage in the left frontal sulci. The hemorrhage was visualized more clearly on the fluid-attenuated inversion recovery sequence of magnetic resonance imaging (A). (B) Digital substraction angiography (DSA) disclosed diffuse arterial irregularities (beading and sausage-like changes). Three-dimensional angiogram allowed optimal depiction of the changes (C). The patient had been recently started on a serotonin-reuptake inhibitor for depression and had smoked marihuana before symptom onset. She had no signs of systemic vasculitis. Cerebrospinal fluid showed elevated red blood cells (1925 cells/mm³) with xanthochromia, mild mononuclear pleocytosis (25 cells/mm³) and elevated protein content (87 mg/dL). A second DSA 1 week later was unchanged. We concluded that it was not possible to discriminate between a benign presentation of primary central nervous system vasculitis and reversible cerebral vasoconstriction syndrome. Brain and meningeal biopsy was contemplated, but instead the patient was treated with prednisone and verapamil for 3 months, at which time the DSA was repeated. The headache subsided over the following 2 weeks. This third DSA showed full resolution of the vascular irregularities. The patient has remained asymptomatic following tapering and discontinuation of prednisone.

Giant Cell (Temporal) Arteritis

♦ Giant cell arteritis (also known as temporal arteritis for its characteristic involvement of the superficial temporal arteries) is a systemic vasculitis of medium-sized and large arteries that affects older adults and elderly patients. The cardinal clinical features of giant cell arteritis are headache, polymyalgia rheumatica, and jaw claudication. Anorexia and malaise are common. The most feared complications are ischemic optic neuropathy, which may result in blindness, and brain infarctions.⁹⁰

♦ Accelerated sedimentation rate and elevation of C-reactive protein strongly support the suspicion of giant cell arteritis. However, temporal artery biopsy is indispensable to make the diagnosis of giant cell arteritis. Typical pathological changes are granulomatous formation (with Langhans giant cells) causing smooth muscle fiber necrosis in the tunica media and destruction of the elastic lamina.⁹¹ These changes may be segmental; thus small biopsy samples may lead to false-negative results.⁹²

♦ Strokes are most often caused by involvement of the extradural vertebral and carotid arteries; a relative preference for the vertebral arteries is reflected in a greater frequency of occipital and brainstem infarctions. Artery-to-artery embolism and hemodynamic compromise are the most likely immediate mechanisms for the infarctions. Strokes are often multifocal and bilateral. Arterial occlusions are uncommon but may occur.⁹³ Intracranial arteritis is less frequent, but its occurrence has been reported^94,⁹⁵ and is well illustrated by our case (Figure 8-19).

♦ Angiography, particularly DSA, can demonstrate lumen irregularities in the most severely involved vessel segments. Special attention should be focused on the distal extracranial vertebral arteries. Areas of severe stenosis can be treated with angioplasty and stenting (Figure 8-19).

♦ Ultrasound (color duplex imaging with frequencies of 5–15 MHz) may be helpful in the diagnosis of temporal arteritis. Indicative findings are the “halo sign” (dark halo around the lumen of the artery likely due to edema of the vessel wall)^96,⁹⁷ and stenosis or occlusion of the temporal artery.⁹⁷ However, the ultrasonographic results are only reliable when examined with the pretest probability of the diagnosis taken into account.⁹⁷ Ultrasound is best used as a screening test to decide whether to proceed with temporal artery biopsy in suspected cases.

♦ Giant cell arteritis is associated with an increased risk for the development of aortic aneurysm.⁹⁸ Consequently, screening for aortic aneurysms with appropriate imaging studies is advisable in these patients.

Figure 8-19 A 65-year-old woman with severe headaches, fatigue, early morning stiffness, and jaw claudication presented with recurrent episodes of transient dysarthria, diplopia, and left-arm incoordination. Temporal arteries were hypertrophic and pulseless. Sedimentation rate and C-reactive protein were markedly elevated. Brain magnetic resonance imaging was unremarkable, but magnetic resonance angiography indicated multifocal areas of intracranial stenosis. Illustrative DSA findings are shown. (A) Left vertebral injection, anteroposterior view, revealing severe stenosis of the distal left vertebral artery near its junction with the basilar artery (arrow). (B) Left carotid injection, lateral view, discloses severe areas of stenosis of the supraclinoid carotid artery (arrow). (C) The distal left vertebral stenosis was considered responsible for the patient’s symptoms, and it was treated with angioplasty and stenting with good angiographic result (arrow). After the intervention, the patient did not have recurrent transient ischemic attacks. Treatment with prednisone led to near-resolution of the headache and systemic symptoms.

SUSAC’S Syndrome

♦ This microangiopathic syndrome, first described and most comprehensively delineated by Susac,^99,¹⁰⁰ manifests with a combination of bilateral sensorineural hearing loss, visual disturbances from retinal artery branch occlusions, and encephalopathy from small brain infarctions (headaches, personality changes, cognitive decline). It is also known as retinocochleocerebral arteriolopathy.¹⁰¹

♦ The disease predominates in young women. Cause is unknown but favorable effects observed after administration of immunomodulatory therapy (steroids, immunoglobulin) suggest an autoimmune (probably inflammatory) mechanism.¹⁰²

♦ The natural evolution of the disorder is characterized by symptomatic flare-ups followed by remissions over a few years, after which the disease tends to subside. However, delayed manifestations are possible (especially retinal infarctions).¹⁰³

♦ Brain MRI shows multiple small infarctions in the subcortical white matter characteristically affecting the corpus callosum (Figure 8-20).¹⁰⁴ Central callosal fibers are most vulnerable and lesions may appear linear (spokes) or rounded (snow balls). Additional locations of involvement include cortex and deep gray nuclei. Acute lesions may enhance and exhibit restricted diffusion; chronic lesions are hypointense on T1-weighted imaging (referred to as T1 holes). Leptomeningeal enhancement may be seen in up to one third of cases.¹⁰⁴

Figure 8-20 This 36-year-old woman presented for evaluation of subacute headaches, behavioral changes, and cognitive impairment. Six months before, she had been diagnosed with right sudden sensorineural hearing loss. Magnetic resonance imaging of the brain showed multifocal white matter lesions best visualized on fluid-attenuated inversion recovery sequence (A–C, open arrows). Preferential callosal involvement with enhancement is observed on the post-gadolinium sagittal T1-weighted sequence (D, solid arrow).

Infectious Vasculitis

♦ Bacterial meningitis rarely causes cerebrovascular complications. Arterial thrombosis may result in cortical infarctions, but cortical vein thrombosis should also be considered in those cases. More proximal branches of the circle of Willis may also be involved with uncontrolled, advanced infection (Figure 8-21).

♦ Central nervous system infection by tuberculosis produces a proliferative and exudative meningitis that preferentially affects the base of the brain. Thus the inflammation may involve the arteries of the circle of Willis, especially in children.¹⁰⁵ Strokes may be ischemic or hemorrhagic.¹⁰⁵^–¹⁰⁸ Most ischemic infarctions are located in the territory of multiple penetrating branches (Figure 8-22), and consequently they are better seen on MRI.¹⁰⁶ Recurrences occur in most severe cases.¹⁰⁷

♦ Varicella zoster virus is the most common viral infection causing strokes. Most often, they complicate varicella in children.¹⁰⁹ In adults, strokes from varicella zoster virus may be seen more frequently in HIV-infected patients.^110,¹¹¹ Medium-sized intracranial vessels are affected by narrowing or occlusion (Figure 8-23).

♦ Cryptococcal meningitis may be associated with ischemic infarctions in patients with HIV (Figure 8-24), but this complication is rare.

♦ Aspergillosis is the fungal infection with higher risk of cerebrovascular complications, ischemic and hemorrhagic, which are often devastating ¹¹² (Figure 8-25). Transplant recipients are predisposed to develop invasive aspergillosis. Direct invasion of the arterial wall by the fungus can be pathologically demonstrated in these cases.¹¹³ Hemorrhages may result from aneurysm formation and rupture.

Figure 8-21 Patient with severe bacterial meningitis caused by Staphylococcus aureus who developed right hemiparesis during his hospitalization. (A) Computed tomography scan showing acute ischemic changes on the right temporal lobe (arrow). (B and C) Diffusion-weighted imaging and apparent diffusion coefficient map reveal that the ischemia involves most of the cortical territory supplied by the right middle cerebral artery (arrows). (D and E) Post-gadolinium T1-weighted sequence displays extensive leptomeningeal enhancement with increased uptake in the right insular area affected by the acute stroke. (F) Magnetic resonance angiography discloses severe stenosis of the right supraclinoid internal carotid artery, A1 and M1 segments (arrows). (G) Digital substraction angiography (right carotid injection, frontal view) confirms the arterial stenosis (arrow) (upper corner shows the left anterior circulation with less severe involvement). (H) Lateral view of the right carotid injection illustrating the paucity of filling in the terminal carotid branches.

Figure 8-22 Example of tuberculous meningitis complicated with ischemic infarction. (A) Noncontrast computed tomography scan showing signs of swelling of the right hemisphere, particularly in the insular region (open arrow) and subtle low attenuation changes of the head of the caudate (solid arrow). (B) Diffusion-weighted imaging sequence of the magnetic resonance imaging confirms the suspicion of acute stroke in the right basal ganglia (solid arrow) (apparent diffusion coefficient map demonstrated low diffusion coefficient in this area). (C and D) Axial and sagittal views of the post-gadolinium T1-weighted sequence display marked enhancement in the right Sylvian region (arrows) caused by the meningitis.

Figure 8-23 A 34-year-old woman with AIDS who presented with acute dysarthria, diplopia, and ataxia. (A) Magnetic resonance imaging scan of the brain showed an acute stroke in the right pons (arrow). Fluid-attenuated inversion recovery sequence is shown. Lesion exhibited restricted diffusion on diffusion-weighted imaging and apparent diffusion coefficient map. (B) Digital substraction angiography reveals severe stenosis of the vertebrobasilar junction and critical stenosis of the midbasilar artery (arrows). Polymerase chain reaction of the cerebrospinal fluid was positive for VHZ.

Figure 8-24 A 38-year-old patient with AIDS presented with fever, headaches, and confusion. On examination, he had mild left hemiparesis. Magnetic resonance imaging (MRI) scan of the brain revealed a focus of restricted diffusion on the right corona radiata, (A) diffusion-weighted imaging and (B) apparent diffusion coefficient map. Cerebrospinal fluid contained a very elevated protein level, mononuclear pleocytosis, and hypoglycorrhachia. India ink smear and cryptococcal antigen testing were positive, indicating Cryptococcus neoformans infection. Despite treatment with amphotericin B and flucytosine, the patient continued to worsen, became unresponsive, and developed bilateral extensor posturing. Repeat MRI of the brain showed marked extension of the bilateral subcortical lesions (C: fluid-attenuated inversion recovery sequence) with multifocal areas of enhancement (D: T1-weighted sequence).

Figure 8-25 A 56-year-old man with diabetes and previous kidney-pancreas transplantation on long-term immunosuppression developed new headache, malaise, neck stiffness, and dizziness over 3 to 4 weeks. Upon hospitalization to another hospital, he was febrile, and soon after admission he became suddenly hemiparetic on the left side. Computed tomography scan of the brain performed at that time revealed multifocal infarctions. Cerebrospinal fluid had predominantly neutrophilic pleocytosis, and the patient was started on a broad regimen of antimicrobials, including antifungal agents. Nonetheless, the patient continued to worsen and became progressively less responsive, prompting transfer to our institution. On our first examination, he was unresponsive and had right third nerve palsy, absent right corneal reflex, and left hemiplegia. Magnetic resonance imaging of the brain disclosed multiple infarctions, involving the right mid and upper brainstem and cerebral hemispheres. Some of these lesions are illustrated by the fluid-attenuated inversion recovery images (A and B). Transesophageal echocardiogram did not shown any vegetations. Digital substraction angiography revealed changes suggestive of vasculitis with occlusion of the right superior cerebellar artery (C, arrow) and irregularities in several arterial segments, including the supraclinoid right internal carotid artery (D, arrow). A sample from a sphenoid sinus biopsy contained abundant hyphae, and Aspergillus fumigatus grew from the cultures of the material. Despite aggressive antifungal therapy, the patient remained comatose and subsequently developed bilateral extensor posturing. Repeat computed tomography scan showed massive hemorrhagic lesions with hydrocephalus (E and F). Family requested withdrawal of life support. Brain necropsy confirmed the diagnosis of invasive aspergillosis with widespread vascular invasion and destruction (G and H).

HIV VASCULOPATHY

♦ Severely immunodepressed HIV-infected patients often have strokes related to uncommon mechanisms, including infectious vasculitis (from concurrent opportunistic infections) and hypercoagulability.¹¹¹

♦ In addition, HIV-infected patients may develop subcortical areas of ischemia from disease involving the microcirculation in the absence of traditional vascular risk factors (Figure 8-26).⁸⁰

♦ Accelerated atherosclerosis might also occur in patients treated with highly active antiretroviral therapy (especially with regimens containing protease inhibitors) who develop metabolic syndrome.⁸⁰ However, the impact of this potential complication on the stroke risk of the HIV population remains to be established.

♦ Pathological studies have shown the presence of small vessel wall thickening, perivascular space dilatation, rarefaction and pigment deposition with vessel wall mineralization, and occasional perivascular inflammatory cell infiltrates without definitive evidence of vasculitis.¹¹⁴ This form of vasculopathy could represent the structural substrate to explain the impairment in cerebrovascular reactivity that has been documented in HIV-infected patients.¹¹⁵

♦ Histologically proved cases of isolated central nervous system vasculitis in HIV-infected patients without opportunistic infectious or tumors are rare; the pathogenic role of HIV in these patients has not been clarified.¹¹⁶

♦ A form of cerebral aneurysmal arteriopathy has been observed in the major vessels of the circle of Willis of HIV-infected children.¹¹⁷^–¹¹⁹ These aneurysmal dilatations are seen in conjunction with medial fibrosis, intimal hyperplasia, and vascular occlusion, leading to areas of infarction. Inflammation involving the vasa vasorum and leading to vessel wall ischemia¹²⁰ and transendothelial migration of HIV-infected monocytes¹²¹ have been quoted as potential mechanisms for the production of these aneurysms.

Figure 8-26 A 34-year-old man with HIV infection and no vascular risk factors was brought by a friend to the emergency department 1 day after acute onset of slurred speech and difficulty controlling his left arm. He denied recreational drug use, and his toxicological screen was negative. On examination, he exhibited dysarthria, perseveration, and apraxia of the left arm. (A) Computed tomography scan of the brain revealed a right caudate infarction (arrow). (B) Brain magnetic resonance imaging scan confirmed the ischemic lesion but also showed an aneurysm in the anterior communicating artery region (arrowhead). (C) Magnetic resonance angiography of the intracranial circulation disclosed only possible narrowing of the right A1 segment (arrow) and the incidental, small saccular anterior communicating artery aneurysm (arrowhead).

RADIATION-INDUCED VASCULOPATHY

♦ Radiation therapy to the neck and head can damage cervical and intracranial vessels, producing luminal stenosis and ischemia.¹²²^–¹²⁴ Accelerated atherosclerosis is responsible for this complication.^123,¹²⁵

♦ The interval between radiation and onset of ischemic symptoms is typically several years.^125,¹²⁶

♦ It is therefore prudent to monitor patients who have undergone neck radiation with periodic carotid ultrasounds.¹²⁷

♦ Radiation-induced vascular lesions tend to be long and multiple. Tandem lesions and multiple vessel involvement are commonly seen (Figure 8-27).

♦ Moyamoya syndrome may develop in patients with severe intracranial carotid disease after radiation of brain tumors at a young age.^124,¹²⁶

♦ Brain infarctions may be caused by arterial-arterial embolism or hemodynamic insufficiency due to critical stenosis or occlusion. Territorial or border-zone infarctions predominate, but small subcortical strokes can also be seen in these patients.

♦ History of radiation is an important factor when counseling patients with carotid disease. Carotid endarterectomy is associated with higher risk of complications (stroke, cranial nerve injury, restenosis, wound infection) in patients with radiation-induced vasculopathy.¹²⁸ Fibrosis obliterating the surgical plane, long lesions exceeding the usual parameters of endarterectomy, and poor tissue healing may explain this increased risk. Thus carotid stenting has been proposed as a valuable alternative in these cases.¹²⁹ However, late symptomatic occlusions may occur after stenting,¹³⁰ and treated patients must be monitored rigorously after the procedure.

Figure 8-27 A 62-year-old woman consulted for evaluation of recurrent episodes of sudden, transient gait imbalance. The duration of the spells ranged between a few minutes and close to 1 hour. She had undergone craniocervical radiation 7 years before for treatment of nasopharyngeal carcinoma. Her vascular risk factors were previous smoking and treated hyperlipidemia. Brain magnetic resonance imaging scan revealed only a chronic small cerebellar infarction and scattered small areas of T2 hyperintensity in both cerebral hemispheres. Magnetic resonance angiography (MRA) of the neck (A) showed stenosis of the proximal cervical left vertebral artery (short arrow), severe stenosis of the midcervical left vertebral artery (long arrow), and a diminutive right vertebral artery throughout its course. MRA of the intracranial circulation (B) showed severe tapering of the basilar artery (arrow). There were also less severe changes affecting the distal cervical and petrous segments of both carotid arteries. MRA of the head and neck preceding radiation therapy proved that all the areas of stenosis had developed since that time.

STROKES FROM SUBSTANCE ABUSE

♦ Intracranial vasculitis from abuse of cocaine or amphetamines is not infrequently suspected on the basis of angiographic changes. However, histologically confirmed cases are rare in the literature.¹³¹^–¹³⁶ Most cases may actually be due to acute, severe (reversible) cerebral vasoconstriction (Figure 8-28).^133,^137,¹³⁸

♦ Ischemic and hemorrhagic strokes may occur, and they may also coexist.

♦ Every vascular distribution may be involved, and strokes may affect cerebral hemispheres, cerebellum, spinal cord, and retina.

Figure 8-28 A 46-year-old man was brought to the emergency department by a friend because of frank behavioral changes. He appeared intoxicated and was quite restless. He could not move the legs to command. (A) Computed tomography scan showed bilateral frontal infarctions with a small hemorrhagic component on the left side. (B) Magnetic resonance imaging confirmed bilateral frontal strokes as illustrated by the fluid-attenuated inversion recovery sequence. (C) Magnetic resonance angiography of the brain showed vasospasm of both anterior and middle cerebral arteries. Toxicological screen was positive for amphetamines.

SICKLE CELL DISEASE

♦ Sickle cell disease (SCD) is a major cause of stroke in children and adolescents. The risk is much higher in children homozygous for the sickle cell gene mutation (SCD-SS).¹³⁹

♦ Ischemic strokes predominate in childhood and intracerebral hemorrhages in young adults.¹³⁹

♦ SCD may produce ischemic infarctions by various mechanisms, including vasculopathy of cervical or major intracranial vessels. Compromise of blood in large intracranial vessels may induce a form of moyamoya syndrome (Figure 8-29).¹⁴⁰ Patients with moyamoya collaterals have increased risk of recurrent strokes.¹⁴⁰

♦ Location and size of the infarctions are also variable.¹⁴¹ Territorial infarctions tend to affect preferentially the middle cerebral artery distribution, but any territory may be affected. Border-zone infarctions can also occur. Small deep ischemic strokes are quite common in the basal ganglia and deep white matter. Border-zone and small infarctions are often asymptomatic. The prevalence of these silent brain lesions on brain MRI exceeds 20% in SCD populations.¹⁴²

♦ Finding on TCD of time-averaged mean blood flow velocities greater than 200 cm/sec in the internal or middle cerebral arteries predicts markedly increased risk of stroke (Figure 8-29).^143,¹⁴⁴ Thus TCD monitoring is advisable in children with SCD, especially if they have anemia, high percentage of sickle hemoglobin, high white blood cell count, hypertension, evidence of brain lesions on imaging scans, or history of chest crisis.^139,¹⁴² The degree of elevation of blood flow velocities should guide the intensity of TCD monitoring (i.e., shorter intervals between studies in patients with higher velocities).¹⁴⁵

♦ Periodic blood transfusions to maintain the sickle hemoglobin less than 30% of the total hemoglobin are effective in reducing the risk of stroke in patients with elevated TCD velocities.¹⁴⁴

♦ Chronic transfusions are necessary. Consequently, iron overload and alloimmunization are important transfusion-related risks. Unfortunately, discontinuation of periodic transfusions guided by improved results on TCD monitoring was not found to be a safe practice.^146,¹⁴⁷