Chapter 8 Uncommon Causes of Stroke

Alejandro A. Rabinstein, Steven J. Resnick

Imaging can be invaluable when evaluating patients with stroke of unknown cause. Sometimes it provides the diagnosis, and sometimes clues to guide additional investigations. This chapter illustrates some of the many infrequent causes of stroke and highlights the ways in which neuroimaging can contribute to their identification. For a more comprehensive review on the topic of uncommon causes of stroke, the reader is referred to a monograph edited by Caplan and Bogousslavsky.¹

The stroke etiologies and mechanisms described in this chapter are seldom encountered in practice. Suspicion is often based on clinical presentation, associated semiological signs, or systemic manifestations. Imaging studies may be crucial to confirm previously suspected uncommon causes. But it may also bring into consideration potential causes that had not been entertained in the differential diagnosis until the imaging findings shed new light on the case. Examples of this situation include spontaneous dissections, different forms of vasculitis, CADASIL, and MELAS among others.

CERVICOCRANIAL ARTERIAL DISSECTIONS

Case Vignette

A 41-year-old man with history of smoking and amphetamine use presented to the emergency department with acute confusion, right gaze preference, left homonymous hemianopia, left hemiplegia (involving face, arm, and leg) and marked left-sided neglect. Three hours before the onset of these deficits, he had complained of severe headache and had tried to go to sleep. Upon awakening, the neurological deficits were established. Computed tomography (CT) scan showed a hyperdense sign in the top of the internal carotid and middle cerebral arteries (Figure 8-1, A–B). The patient was emergently taken to the angiographic suite, and a catheter angiogram revealed occlusion of the right internal carotid artery 1.5 to 2 cm beyond its origin (Figure 8-1, E). No revascularization therapy was attempted because of the site of the occlusion, acceptable collateral pathways (the anterior communicating artery and posterior communicating arteries were open), and because the patient started seizing and had to be rapidly transferred to the intensive care unit for anticonvulsive treatment. His blood pressure was augmented with fluids and vasopressors, but he developed a large stroke in the middle cerebral artery territory, as shown on the magnetic resonance imaging (MRI) scan performed within 24 hours of admission (Figure 8-1, C–D). He recovered well but was still moderately disabled at 3-month follow-up. At that time, a magnetic resonance angiogram (MRA) showed persistent occlusion of the right internal carotid artery (Figure 8-1, F).

Figure 8-1 (A) Nonenhanced head computed tomography scan showing a hyperdense vessel sign in the top of the right internal carotid artery (arrow). (B) This sign extends into the horizontal segment of the right middle cerebral artery (arrow). (C) Diffusion-weighted sequence of the magnetic resonance showing a large area of bright signal in the territory of the right middle cerebral artery (apparent diffusion coefficient map showed corresponding dark signal in that region, indicating restricted diffusion from cellular edema due to acute ischemia). (D) Fluid-attenuated inversion recovery sequence shows early signs of cortical ischemia in the right hemisphere. (E) Digital substraction angiography displaying tapering and occlusion of the right internal carotid artery1.5 to 2 cm above its origin (arrow). (F) Magnetic resonance angiography 3 months later demonstrating persistent occlusion of the vessel (arrow).

♦ Dissections represent one of the most common causes of ischemic stroke in the young (under age 45).²

♦ They should be suspected in trauma patients presenting with focal neurological symptoms or Horner’s sign (due to damage of the sympathetic plexus surrounding the carotid wall). However, many cases occur in the absence of obvious precipitating injury. In fact, in these “spontaneous” cases, it is not uncommon to identify minor trauma or predisposing activities (such as chiropractic maneuvers, roller-coaster rides, certain sports, or other factors associated with sudden or prolonged hyperextension or extension/torsion of the neck). Abnormalities of connective tissue, particularly elastic fibers, have been documented in ultrastructural analysis of skin biopsies of patients with spontaneous dissections.³ Conditions disrupting the integrity of the connective tissue in the arterial wall predispose to dissection; these include fibromuscular dysplasia (discussed later in the chapter), Marfan syndrome, Ehlers-Danlos type III, and alpha-1 antitrypsin deficiency, among others.⁴^–⁶ Familial cases have also been reported.^7,⁸

♦ Headache and neck pain preceding or accompanying the symptoms and signs of brain ischemia should raise suspicion for arterial dissection.⁹

♦ 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.