Pathophysiologic and Imaging Characteristics Border Zone Infarcts Pathophysiologic and Imaging Characteristics

Classification of Border Zone Infarcts

Watershed infarcts occur at the border zones between major cerebral arterial territories as a result of hypoperfusion. There are two patterns of border zone infarcts: Cortical border zone infarctions Infarctions of the cortex and adjacent subcortical white matter located at the border zone of ACA/MCA and MCA/PCA Internal border zone infarctions Infarctions of the deep white matter of the centrum semiovale and corona radiata at the border zone between lenticulostriate perforators and the deep penetrating cortical branches of the MCA or at the border zone of deep white matter branches of the MCA and the ACA.

Color overlays on axial T2 MRI of normal cerebrum show probable locations of external (blue) and internal (red) border zone infarcts Color overlays on axial T2-weighted magnetic resonance (MR) images of normal cerebrum show probable locations of external (blue) and internal (red) border zone infarcts.

Contour map of frequency of affected sites in the IBZ (A) and CBZ (B) infarcts. The location of the IBZ can vary along the lateral ventricle, whereas the CBZ is distributed more heterogeneously as wedged areas that extend from the frontal and occipital horn of the lateral ventricle or within the paramedian white matter at the supraventricular level.

Location of regions of interest Location of regions of interest. These are divided into six areas on the basis of the idealized standard concept of arterial distributions of the brain, as follows: territories of the ACA, MCA, PCA, anterior BZ (between the territories of the ACA and MCA), posterior BZ (between the territories of the MCA and PCA), and internal BZ (between the territories of the cortical branches and penetrators of the MCA). These are divided into six areas on the basis of the idealized standard concept of arterial distributions of the brain, as follows: territories of the ACA, MCA, PCA, anterior BZ (between the territories of the ACA and MCA), posterior BZ (between the territories of the MCA and PCA), and internal BZ (between the territories of the cortical branches and penetrators of the MCA).

Pathophysiology of Border Zone Infarcts Border zone infarcts involve the junction of the distal fields of two nonanastomosing arterial systems . The conventional theory implicates hemodynamic compromise produced by repeated episodes of hypotension in the presence of a severe arterial stenosis or occlusion. The lower perfusion pressure found within the border zone areas in this setting confers an increased susceptibility to ischemia, which can lead to infarction. Radiologic studies also support the hypothesis that border zone infarcts distal to internal carotid artery disease are more likely to occur in the presence of a noncompetent circle of Willis.

Pathophysiology of Border Zone Infarcts Recent study suggests an association between border zone infarction and microemboli, and embolic material has been found within areas of border zone infarction in autopsy series. Border zone infarction may be better explained by invoking a combination of two often interrelated processes: hypoperfusion and embolization.

Pathophysiology of Border Zone Infarcts Hypoperfusion, or decreased blood flow, is likely to impede the clearance (washout) of emboli. Because perfusion is most likely to be impaired in border zone regions, clearance of emboli will be most impaired in these regions of least blood flow. Severe occlusive disease of the internal carotid artery causes both embolization and decreased perfusion. Cardiac disease is often associated with microembolization from the heart and aorta with periods of diminished systemic and brain perfusion. This theory, although it seems reasonable, remains unproved and has been challenged on many accounts.

External Border Zone Infarcts The external, cortical border zones are located between the anterior, middle, and posterior cerebral arteries and are usually wedge-shaped or ovoid . Their location may vary with differences in the arterial supply. It is sometimes difficult to determine whether or not a border zone infarct on the basis of the location of the infarct in relation to the vessels on a CT or MRI. Because of this extensive anatomic variation, minimum and maximum distribution territories of each vessel have been defined. It is common to describe a cortical infarct as a “territorial” infarct if it lies completely within the expected or possible maximum area of a vascular territory or as a “potential” infarct if it is outside these maxima . The location of cortical border zones may vary because of the development of leptomeningeal collaterals. The anatomy of cortical border zones can be complex, with marked variability due to individual differences in the territories supplied by the major arteries of the brain.

Coronal FLAIR MRI show the distribution of external border zone infarcts at the junctions of the ACA and MCA territories (a, b) Coronal fluid-attenuated inversion recovery MR images show the distribution of external (cortical) border zone infarcts at the junctions of the anterior cerebral artery and middle cerebral artery territories (a) and the middle cerebral artery and posterior cerebral artery territories (b). (c) Diffusion-weighted MR images show a cortical border zone infarct at the junction of the anterior cerebral artery and middle cerebral artery territories. Angiography of the right-sided common carotid and internal carotid arteries in the same patient showed normal vessels with no occlusion or stenosis.

Coronal FLAIR MRI show the distribution of external (cortical) border zone infarcts at the junctions of the PCA and MCA territories (a, b) Coronal fluid-attenuated inversion recovery MR images show the distribution of external (cortical) border zone infarcts at the junctions of the anterior cerebral artery and middle cerebral artery territories (a) and the middle cerebral artery and posterior cerebral artery territories (b). (c) Diffusion-weighted MR images show a cortical border zone infarct at the junction of the anterior cerebral artery and middle cerebral artery territories. Angiography of the right-sided common carotid and internal carotid arteries in the same patient showed normal vessels with no occlusion or stenosis.

DWI show a cortical border zone infarct at the junction of the ACA and MCA territories. Angiography of the right-sided common carotid and internal carotid arteries in the same patient showed normal vessels with no occlusion or stenosis. (a, b) Coronal fluid-attenuated inversion recovery MR images show the distribution of external (cortical) border zone infarcts at the junctions of the anterior cerebral artery and middle cerebral artery territories (a) and the middle cerebral artery and posterior cerebral artery territories (b). (c) Diffusion-weighted MR images show a cortical border zone infarct at the junction of the anterior cerebral artery and middle cerebral artery territories. Angiography of the right-sided common carotid and internal carotid arteries in the same patient showed normal vessels with no occlusion or stenosis.

Causal Mechanisms The mechanism of external border zone infarction has been widely debated. Many studies have documented hemodynamic abnormalities in the anterior watershed or frontal cortical border zone. However, in many recent studies, no evidence of such hemodynamic impairment was found. The cerebral or carotid vessels may appear entirely normal or show mild or moderate narrowing without hemodynamic compromise. Isolated cortical border zone infarcts may be embolic in nature and are less frequently associated with hemodynamic compromise.

Microemboli from the heart or atherosclerotic plaques in major arteries may preferentially propagate to cortical border zones, which have lower perfusion than other areas of the vasculature, and, thus, a limited ability to wash out these emboli. Many patients with cortical border zone infarcts have concomitant smaller cortical infarcts. These findings support the hypothesis that an embolic mechanism plays a crucial role in the pathogenesis of external border zone infarcts.

Internal Border Zone Infarcts Internal border zone infarcts appear in multiples, in a rosarylike pattern. This pattern was described as a series of three or more lesions, each with a diameter of 3 mm or more, arranged in a linear fashion parallel to the lateral ventricle in the centrum semiovale or corona radiata. Internal border zone infarcts are classified on the basis of their radiologic appearance as either confluent or partial. Partial infarcts are usually large, cigar shaped, and arranged in a pattern resembling the beads of a rosary, parallel and adjacent to the lateral ventricle. The duration of hemodynamic compromise has been postulated as the cause of the varied radiologic appearances, with a brief episode of compromise leading to a partial infarct, and a longer period of compromise, to confluent infarcts. Confluent internal border zone infarcts may be manifested by a stepwise onset of contralateral hemiplegia. They also may be associated with a poorer recovery than is typical for partial infarcts.

Color overlay on a coronal MIP image from CTA in a healthy volunteer shows the probable location of the internal border zone (blue dots) (a) Color overlay on a coronal MIP image from CT angiography in a healthy volunteer shows the probable location of the internal border zone (blue dots). (b) Diffusion-weighted MR images, obtained in a 52-year-old woman with progressive weakness and numbness for 6 months and a complete foot drop, show multiple internal border zone infarcts in a rosarylike pattern along the left centrum semiovale. (c) Left internal carotid angiogram in the same patient demonstrates severe stenosis of the M1 segment of the left middle cerebral artery.

Three consecutive CT-images of a patient with an occlusion of the right internal carotid artery. The hypoperfusion in the right hemisphere resulted in multiple internal border zone infarctions. This pattern of deep watershed infarction is quite common and should examine the carotids.

DWI, obtained in a 52-year-old woman with progressive weakness and numbness for 6 months and a complete foot drop, show multiple internal border zone infarcts in a rosarylike pattern along the left centrum semiovale (a) Color overlay on a coronal MIP image from CT angiography in a healthy volunteer shows the probable location of the internal border zone (blue dots). (b) Diffusion-weighted MR images, obtained in a 52-year-old woman with progressive weakness and numbness for 6 months and a complete foot drop, show multiple internal border zone infarcts in a rosarylike pattern along the left centrum semiovale. (c) Left internal carotid angiogram in the same patient demonstrates severe stenosis of the M1 segment of the left middle cerebral artery.

Left internal carotid angiogram in the same patient demonstrates severe stenosis of the M1 segment of the left MCA (a) Color overlay on a coronal MIP image from CT angiography in a healthy volunteer shows the probable location of the internal border zone (blue dots). (b) Diffusion-weighted MR images, obtained in a 52-year-old woman with progressive weakness and numbness for 6 months and a complete foot drop, show multiple internal border zone infarcts in a rosarylike pattern along the left centrum semiovale. (c) Left internal carotid angiogram in the same patient demonstrates severe stenosis of the M1 segment of the left middle cerebral artery.

Axial DWI (A) and FLAIR (C) images demonstrate centrum infarcts in a rosary configuration consistent with internal border zone infarcts in a patient with hypotension. Note left superior parietal lobule infarct in the expected location of the MCA/PCA cortical border zone.

Small infarctions in the right hemisphere in the deep borderzone (blue arrowheads) and also in the cortical borderzone between the MCA- and PCA-territory (yellow arrows).There is abnormal signal in the right carotid (red arrow) as a result of occlusion. In patients with abnormalities that may indicate borderzone infarcts, always study the images of the carotid artery to look for abnormal signal.

Infarctions in the deep borderzone and in the cortical borderzone between the ACA- and MCA-territory. The abnormal signal intensity in the right carotid is the result of an occlusion.

man-in-the-barrel syndrome (MIBS) Disproportionate weakness of both arms (especially proximally) and relatively normal mobility of face and legs, as though the trunk of the patient is stuck in a barrel

MIBS The dominant mechanistic theory explaining MIBS is that of bilateral symmetric watershed infarction in the region perfused by medullary arteries from the superficial pial plexus and deep penetrating arteries from the basal cerebral arteries. Although there have been several papers decribing the CT or MR features of watershed infarcts between the territories perfused by MCA and ACA, especially the corona radiata and centrum semiovale, it is unclear exactly which focal neural pathway is disrupted that directly leads to the clinical presentation of MIBS. It is postulated that there is a threshold for the amount of confluently affected paraventricular white matter above which MIBS may become manifest.

Internal border zone infarcts must be differentiated from superficial perforator (medullary) infarcts, which may have a similar appearance on MRI. Superficial perforator infarcts, which are caused by the occlusion of medullary arteries from pial plexuses, are smaller, superficially located, and widely scattered, whereas internal border zone infarcts tend to localize in paraventricular regions. Superficial perforator infarcts are associated with less severe vascular stenoses and a better prognosis than internal border zone infarcts. Because of the difficulty of differentiating between the two types of infarcts on radiologic images, they have sometimes been collectively described as subcortical white matter infarcts, but that term is diagnostically nonspecific.

Causal Mechanisms In contrast to external border zone infarcts, internal border zone infarcts are caused mainly by arterial stenosis or occlusion, or hemodynamic compromise. Medullary penetrating arteries are the most distal branches of the internal carotid artery and have the lowest perfusion pressure. The deep perforating lenticulostriate arteries have little collateral supply, and there are no anastomoses between the deep perforators and the white matter medullary arterioles. Therefore, the centrum semiovale and corona radiata are more susceptible than other regions to ischemic insults in the setting of hemodynamic impairment.

Clinical Course Internal border zone infarcts are associated with a poor prognosis and clinical deterioration. The results of DWI studies suggest that patients with internal border zone infarcts have an increased risk for stroke during the first few days after infarction. Perfusion studies in patients with such infarcts have shown a far greater area of misery perfusion than is reflected on DWI. Involvement of the adjacent cortex also has been found on perfusion images. The typically small internal border zone infarcts represent the “tip of the iceberg” of decreased perfusion reserve and may be predictive of impending stroke.

Posterior External (Cortical) Border Zone Infarcts Anterior external border zone infarcts are more common than posterior ones because of the high prevalence of internal carotid artery disease. VB system disease with superimposed fetal circulation (ie, a fetal-type posterior cerebral artery) may lead to posterior external border zone infarcts. Unilateral posterior external border zone infarcts have been related to cerebral emboli either of cardiac origin or from the common carotid artery, whereas bilateral infarcts are more likely to be caused by underlying hemodynamic impairment (vascular stenosis).

Axial DWI and ADC map show bilateral posterior cortical border zone infarcts Axial diffusion-weighted MR image and apparent diffusion coefficient map show bilateral posterior cortical border zone infarcts.

Small infarctions in the deep borderzone and in the cortical borderzone between the MCA- and PCA-territory in the left hemisphere.

Border Zone Infarcts in the Cerebellum The infarction is due to stenosis or embolism of the vessels. The source of embolism could be atherosclerotic disease or dissection in a vertebrobasilar artery or a cardiac condition (eg, right heart thrombus in paradoxical embolism). Often, these small border zone lesions coexist with large territorial lesions. The management of border zone infarcts in the cerebellum is similar to that of territorial cerebellar infarcts .

Schematic shows the border zones of the lateral (dark green) and medial (light green) SCA, AICA (red), and lateral (dark blue) and medial (light blue) postePICA. Schematic shows the border zones of the lateral (dark green) and medial (light green) superior cerebellar arteries, anterior inferior cerebellar artery (red), and lateral (dark blue) and medial (light blue) posterior inferior cerebellar arteries. Orange = anteromedial brainstem supply from anterior spinal, vertebral, and basilar arteries; yellow = lateral supply from basilar artery. (Sources.—References 31 and 32.)‏

Infarct, borderzone, multiple

(A) Anterior cortical borderzone infarct (CBI). (B) Posterior CBI (A) Anterior cortical borderzone infarct (CBI). (B) Posterior CBI. (C) Combined anterior and posterior CBI. (D,E) Internal borderzone infarcts. (F) Combined internal borderzone infarct and territorial infarct.

Watershed Infarcts Hypoperfusion of CNS – post CABG, cardiac arrest, respiratory hypoxia, bilateral carotid stenosis Border zone infarcts – MCA-PCA: bilateral parieto-occipital infarcts altitudinal filed defect, optic ataxia, cortical blindness dyslexia, dyscalculia, dysgraphia, impaired memory – ACA-MCA: sensorimotor impairment (man-in-a-barrel) impaired saccades – PICA-AICA-SCA

Conclusions Internal (subcortical) border zone infarcts, which typically appear in a linear rosarylike pattern in the centrum semiovale, are caused mainly by hemodynamic compromise. External (cortical) border zone infarcts are believed to be caused by embolism, sometimes with associated hypoperfusion. External border zone infarcts usually follow a benign clinical course, whereas internal border zone infarcts are associated with higher morbidity and a higher risk for future stroke. Different therapeutic approaches may be required to prevent early clinical deterioration in patients with different types of border zone infarcts.

52-year-old male, unknown past medical history, found unresponsive, later awake but poor response to stimuli with significant decrease of power in both arms, especially proximally A: Inflammatory B: Infectious C: Vascular D: Trauma

Which vascular distribution best fits to the imaging findings A: MCA B: ACA C: ACA and MCA D: MCA and PCA A: Neurological malignant syndrome B: Restless legs syndrome C: Guillain Barre syndrome D: Man-in-the-Barrel syndrome

Man-in-the-barrel syndrome (MIBS) Watershed infarcts have a characteristic distribution in the brain. Brachial diplegia as a clinical sign is not specific for bilateral watershed infarcts but there is a known association.

33-year-old woman with rapidly declining mental status one day after a car crash T2WI and FLAIR images show punctate areas of high signal in parasagittal white matter. (Fig. 1A) These lesions are also bright on DWI. (Fig. 1B) The abnormalities on DWI tend to rapidly clear. This is thought to be due to further fat emboli fragmentation and passing past the brain capillary bed. Mortality is between 10-20% and patients who survive may show nearly no sequelae.

Cerebral Fat Emboli The incidence of cerebral fat embolism (CFE) is unknown. It occurs more commonly (80%) after blunt trauma and is particularly associated with long bone fracture. Patients may experience a period of normal neurological status followed by rapid deterioration, sometimes after manipulation of the fracture. Patients may develop acute respiratory distress, and retinal hemorrhages may become evident. A right-to-left cardiac shunt is not a prerequisite. The small fat globules may further fragment and because they are deformable and may pass through an intact pulmonary capillary bed. They reach the deep arterial territory in the brain, which commonly involves the deep white matter (simulating watershed infarctions).

65 year old with mental status change