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Posterior Reversible Encephalopathy Syndrome and Other Cerebrovascular Syndromes
Sara K. Rostanski
Claire S. Riley
Joshua Z. Willey
POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME
The posterior reversible encephalopathy syndrome (PRES) has been evolving as a clinical entity for the last 10 years. Several terms have now been used interchangeably to define PRES, including reversible posterior leukoencephalopathy syndrome (RPLS), or by naming the underlying clinical cause. PRES is now recognized as a clinicoradiologic syndrome rather than a distinct disease entity with multiple different etiologies, which share several common features with the reversible cerebral vasoconstriction syndrome.
Limited data exist to describe the epidemiology of this condition. The literature has mostly been centered around case reports and case series.
Disorders that cause PRES have in common cerebral injury due to failure of the cerebral vasculature to adapt to changes in blood pressure or cerebral hemodynamics or an excessive vascular reactivity in cerebral arterioles. The hallmark clinical entities that most often cause PRES are hypertensive encephalopathy and eclampsia (see also Chapter 124
). A focal process that may share some features of this condition is cerebral hyperperfusion syndrome occurring after carotid endarterectomy. In patients with chronic hemodynamic failure, distal arterioles tend to dilate to reduce cerebral vascular resistance; in clinical scenarios of a sudden increase in cerebral blood flow, these maximally dilated cerebral arteries may not be able to adapt further to changes in cerebral blood flow, leading to cerebral edema and hemorrhage. In addition to impaired autoregulation in the face of hypertension and hyperperfusion, in many cases, PRES is also associated with abnormal capillary permeability in the brain and large-vessel proximal vasoconstriction detectable by angiography. Up to 87% of patients with PRES have diffuse vasoconstriction if studied with angiography, hence, PRES and reversible cerebral vasoconstriction syndrome (discussed later) often overlap and are felt in many cases to share a common pathogenesis. The result is vasogenic edema that preferentially affects the posterior hemispheres of the brain and the white matter more than the gray matter. Interspersed in this picture are scattered microinfarcts and microhemorrhages. The most severe cases can manifest as massive global cerebral edema with transtentorial herniation or larger infarcts or hemorrhages.
The clinical syndrome associated with PRES is dependent on the underlying cause, although regardless of underlying etiology, common clinical symptoms include headache, seizures, loss of visual acuity including blindness, nonlocalizing confusion, and somnolence (Table 43.1
). The neurologic examination will not reveal localizing findings on the mental status, although cases of cortical blindness and Balint syndrome may occur due to involvement of the occipital lobes (Fig. 43.1
). Other described findings include visual field cuts, loss of visual acuity, papilledema, and mild hemiparesis. More prominent bulbar and cerebellar symptoms have been described in case series where the pathology is restricted to the brain stem. A larger variety of clinical syndromes, which can be localized anywhere in the cerebral hemisphere occurs in the context of severe cases with cerebral infarction or hemorrhage. PRES leading to edema primarily involving the brain stem has also been described (Fig. 43.2
TABLE 43.1 Approximate Frequency of Clinical Features of Posterior Reversible Encephalopathy Syndrome
Nausea and vomiting
REVERSIBLE CEREBRAL VASOCONSTRICTION SYNDROME
In 2007, the term reversible cerebral vasoconstriction syndrome
(RCVS) was proposed to encompass several previously described miscellaneous cerebral vasculitic disorders, which included
Call-Fleming syndrome, thunderclap headache-associated vasoconstriction, postpartum angiopathy, migraine angiitis, and cerebral vasospasm caused by cocaine, amphetamines, sumatriptan, and other serotonergic and sympathomimetic drugs.
FIGURE 43.2 FLAIR images of posterior reversible encephalopathy syndrome presenting with prominent brain stem involvement (A-D). Nine days later, the lesions had significantly resolved (E-H).
RCVS is characterized by a monophasic course of diffuse segmental constriction of cerebral arteries that resolves spontaneously within weeks to months. Although the angiographic findings may be indistinguishable from primary angiitis of the central nervous system (PACNS), RCVS is not a chronic condition that requires long-term immunosuppression. RVCS is not a form of vasculitis because vessel wall inflammatory infiltrates do not occur, although the angiographic findings are similar. The cerebrospinal fluid (CSF) is normal, and the clinical course tends to be benign given the marked and extensive angiographic abnormalities that can occur.
Due to the lack of epidemiologic studies, the true incidence of RCVS has not been estimated. Since 2007, there has been a surge in the number of RCVS-related publications likely due to increased awareness.
Other than vasoconstriction, there is no known unifying pathologic mechanism that underlies RCVS because it is a syndrome rather than a distinct disease entity. An aberrant sympathetic response of cerebral vasculature is one of the preferred hypotheses resulting in an unpredictable and short-lived failure of normal regulation of cerebral arterial tone. This leads to segmental vasoconstriction and vasodilatation in small cerebral vessels, often triggering thunderclap headaches due to stretching of vasa nervorum within the vessel walls.
RCVS appears to be an intrinsic process that can be triggered by a wide variety of pharmacologic and physical stimuli (Table 43.3
). Different precipitating factors, including vasoconstrictive drug exposure (serotonergic or adrenergic agents), recreational drugs, and postpartum state are associated with RCVS in around 50% of cases. Head injuries and neurosurgical interventions have also been associated with RCVS.
PRES occurs in a substantial proportion of patients with RCVS. Hence, a shared pathophysiology between these two overlapping syndromes is highly probable. Severe forms of RCVS are likely to lead to PRES. In the past, it is likely that many of the cases termed central nervous system vasculitis and benign angiitis of the central nervous system may have actually referred to RCVS.
RCVS affects mainly women, with a mean age at onset of 40 years. In over 80% of cases, patients present with a sudden onset of single or recurrent thunderclap headaches. These headaches differ from those associated with aneurysmal subarachnoid hemorrhage (SAH) because they are usually short lived and intermittent, whereas SAH causes unremitting headaches that persist for days with prominent meningismus. Seizures occur and transient focal deficits in the form of visual, sensory, dysphasic, or motor deficits occur in
approximately 20% of patients at some point during the course of the illness, either alone or in combination. The focal deficits usually last minutes to hours but in some cases are persistent and associated with focal infarction. Blood pressure surges occur in 40% of patients; it is unclear if these elevations are related to the primary condition or are a reaction to pain or neurologic injury. Rupture or reperfusion injuries involving small leptomeningeal arteries may cause convexity SAHs.
TABLE 43.2 Etiologies of Posterior Reversible Encephalopathy Syndrome
Fibromuscular dysplasia (FMD) is a noninflammatory, nonatherosclerotic arteriopathy of medium-sized vessels of unknown cause. Although it can affect any vascular bed, the renal and cervicocranial carotid and vertebral arteries are most commonly involved.
Cervicocranial FMD is a rare condition, with one autopsy study citing an overall prevalence of 0.02%. Rates for renovascular FMD are higher, with prevalence estimates of up to 4% shown in several studies. In confirmed FMD cases, renal involvement is generally seen in up to 65% of cases, with cerebrovascular involvement in 25% to 30% of cases. In a series of 1,100 FMD patients, women were twice as frequently affected as men with Caucasians disproportionately affected. The mean age of diagnosis in patients with cerebrovascular involvement is 50 years, older than for renovascular involvement. Approximately 10% of cases are felt to be familial. Diagnosis is frequently delayed, with up to 9 years elapsing from initial symptoms to diagnosis.
There are three types of FMD, characterized by arterial layer of involvement: intimal fibroplasia, medial dysplasia, and adventitial fibroplasia. Intimal fibroplasia occurs in up to 10% of cases and results from accumulation of abnormal subendothelial mesenchymal cells, which project into the vessel lumen. This commonly results in areas of smooth, focal stenosis or long tubular stenosis. Adventitial fibroplasia, where the fibrous adventitia is replaced by collagen, is very rare.
Medial dysplasia is the most common, with three distinct subtypes recognized: medial fibroplasia, perimedial fibroplasia, and medial hyperplasia. Medial fibroplasia is the most common and accounts for up to 80% of cases.
The main histologic hallmark is disruption of smooth muscle cells, which are replaced by fibroblasts and collagen. There is frequently secondary disruption of the internal elastic lamina, which may lead to aneurysm formation. The alternating areas of medial disruption give rise to the commonly seen “string of beads” radiographic appearance, where areas of stenosis are admixed with dilated areas that are of larger caliber than the original vessel. Perimedial fibroplasia results from abnormal collagen deposition between the media and adventitia, leading to areas of stenosis with preserved internal elastic lamina. Radiographic appearance may be similar to medial fibroplasia, but the “beads” are of smaller diameter than the original vessel.
Although the etiology is unknown, FMD is associated with a variety of diseases including alpha-1 antitrypsin deficiency, Marfan syndrome, and Alport syndrome. Given the female preponderance, hormonal links have been posited, although evidence is lacking. Ischemia at the level of the vasa vasorum has been suggested as a possible underlying factor, although this remains unproven.
Cervicocranial FMD is frequently an incidental finding and rates of neurologic symptoms vary. Neurologic complications mainly arise due to ischemic or hemorrhagic symptoms that result from stenosis, thrombosis, dissection, or aneurysmal formation. Carotid-cavernous fistulas have also been described. Severe stenosis can cause distal hypoperfusion. Thrombotic occlusion of a stenotic vessel or distal embolism can lead to hemispheric ischemic symptoms. SAH can result from intracranial aneurysm rupture. Spontaneous cervical dissection can also occur, and headache, dizziness, carotidynia, pulsatile tinnitus, and Horner syndrome are all symptoms commonly seen with cervicocranial FMD. Dissection may be more common in Asian populations.
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