References for this review were identified using PubMed, with search terms “hyperperfusion, syndrome”, “carotid endarterectomy”, “CHS”, “cerebral blood flow”, and “hypertension”, and analysis of the reference lists of the articles retrieved. Case reports and case series were not discarded in the analysis, but it is obvious that epidemiological data cannot be derived from these publication types. There were no date limitations, and the last search was done in August 2005. Some studies of
Personal ViewCerebral hyperperfusion syndrome
Introduction
Carotid endarterectomy is treatment of choice for symptomatic stenosis of the carotid artery. Reanalysis of data from three large randomised trials on carotid endarterectomy showed that surgery is of some benefit for patients with symptomatic stenosis, and highly beneficial for those with symptomatic stenosis of 70% or more without near occulsion.1 Recently the Asymptomatic Carotid Surgery Trial showed that in asymptomatic patients younger than age 75 years with carotid stenosis of 70% or more, immediate carotid endarterectomy halved the 5 year stroke risk from 12% to 6%. These benefits only exist when the complication rate is kept below 3%.2 Carotid angioplasty with stenting is a promising alternative to carotid endarterectomy,3 but carotid endarterectomy remains the treatment of choice.
Cerebral hyperfusion syndrome (CHS) can occur after carotid endarterectomy or carotid angioplasty with stenting, and is characterised by throbbing ipsilateral frontotemporal or periorbital headache, and sometimes diffuse headache, eye and face pain, vomiting, confusion, macular oedema, and visual disturbances, focal motor seizures with frequent secondary generalisation, focal neurological deficits, and intracerebral or subarachnoid haemorrhage. Although most patients have mild symptoms and signs, progression to severe and life-threatening symptoms can occur if CHS is not recognised and treated adequately. Because CHS is a diagnosis based on several non-specific signs and symptoms, patients may be misdiagnosed as having one of the better-known causes of perioperative complications like thromboembolism. However, knowledge of CHS among physicians is limited.4 In this paper we review research on CHS.
Section snippets
History
Reactive hyperaemia was first described in 1925 during reperfusion after vascular occlusion of limbs,5 overabundant cerebral blood flow relative to metabolic needs was termed “luxury perfusion syndrome”6 in 1966, and in 1978 the “normal-perfusion-pressure-breakthrough” theory7 was published as an explanation for cerebral oedema and haemorrhage after excision of a cerebral arteriovenous malformation. Sundt and colleagues8 described CHS after carotid endarterectomy. CHS has also been described
Epidemiology
There are asymptomatic increases in ipsilateral cerebral blood flow (20–40% over baseline) in most patients immediately after carotid endarterectomy that last for several hours.8, 19, 20 In some patients, severe long-lasting hyperaemia occurs with increases of cerebral blood flow to levels of 100–200% over baseline,8 which is often maximal 3–4 days after surgery, falls to a steady state by the sixth or seventh postoperative day, but can last 1–2 weeks.20, 21, 22 Hyperperfusion (most commonly
Normal cerebral autoregulation
The effects of carbon dioxide and cerebral autoregulation maintain cerebral blood flow at a blood pressure range of 60–160 mm Hg. The effect of carbon dioxide on the cerebral arteries is most pronounced in smaller arteries (diameter 0·5–1·0 mm), whereas arteries with a diameter of 2·5 mm or more (eg, the carotid artery) show no substantial change.52 Cerebral autoregulation has a myogenic and a neurogenic component. In myogenic autoregulation, increased intravascular pressure results in
Pathophysiology of CHS
Three mechanisms may contribute to the pathophysiology of hyperperfusion and CHS. First, impaired autoregulation could mean that increases in cerebral blood flow after carotid endarterectomy are not counteracted by paralysis of cerebral autoregulatory mechanisms.8, 55 That diminished cerebrovascular reactivity or reserve capacity (percentage rise in blood flow velocity in the middle cerebral artery after acetazolamide) can identify patients at risk for hyperperfusion supports this theory.23
Pathology
Cerebral hyperperfusion sufficient to produce breakthrough of autoregulation results in transudation of fluid into the pericapillary astrocytes and interstitium. Permeability increases via pinocytosis (introduction of fluids into the cytoplasm by enclosing them in membranous vesicles at the cell surface), in an attempt to prevent haemorrhage. The resulting oedema is hydrostatic in nature56 and predominant in the vertebrobasilar circulation territory in both CHS and hypertensive encephalopathy,71
Potential risk factors for CHS
Many conditions may be predisposing factors for CHS.4, 8, 23, 24, 25, 27, 29, 33, 34, 37, 38, 39, 40, 44, 46, 47, 60, 72, 74, 75, 76, 77, 78, 79, 80, 81, 82 Whether all the factors mentioned are risk factors for CHS, or simply factors predisposing for atherosclerosis, and therefore commonly present in patients with CHS is questionable (panel 2). Diminished cerebrovascular reserve, postoperative hypertension, and hyperperfusion lasting more than several hours to days after carotid endarterectomy
Imaging and functional techniques in CHS
There are two approaches used to try to identify patients at risk for CHS: preoperative demonstration of cerebral hypoperfusion, or either peroperative or postoperative demonstration of cerebral hyperperfusion. CT, MRI, and transcranial doppler are most widely used, but less commonly used techniques, such as single-photon emission CT and PET can also be useful in the diagnosis of CHS. Routine use of electroencephalography for the purpose of diagnosing hyperperfusion and CHS is not useful (
Prevention of CHS
Timing of surgery, type and dose of anaesthesia, treatment of hypertension, and adequate instructions for patients after hospital discharge. Pretreatment with the free-radical scavenger edaravone could also be considered.66
Work-up of patients with symptoms after carotid endarterectomy
Apart from identifying patients at risk, the work-up of a symptomatic patient after carotid endarterectomy is a challenge. We propose use of an algorithm for the work-up of patients with symptoms suggestive of CHS after carotid endarterectomy (figure 2). Once symptoms after carotid endarterectomy have occurred, differentiation between surgically treatable causes (for example, occlusion of the operated vessel), emboli, low-flow state (ischaemia or infarction), or high-flow state (CHS) is
Therapy
Because blood flow is pressure dependent in patients with CHS, and symptoms can disappear immediately with reduction of the systemic arterial blood pressure, most researchers recommend strict control of blood pressure in CHS. Drugs that have no direct effects on cerebral blood flow, and those that give some degree of cerebral vasoconstriction could be advantageous on theoretical grounds. Many drugs commonly used for treatment of hypertension, such as direct vasodilators (for example,
Prognosis
Prognosis is dependent on the timing and accuracy of diagnosis and treatment. Conclusions on prognosis are derived from a few patients with CHS, all of whom were diagnosed in different postoperative phases and treated differently. Although most patients—perhaps those diagnosed and treated early—seem to recover completely, some studies indicate that nearly 30% of patients with (severe CHS, or those diagnosed late) CHS remain partly disabled,35 and mortality rates of 50% have been reported.25
Conclusions and suggestions
Patients with substantial cerebral hypoperfusion because of carotid stenosis benefit from intervention in the form of carotid endarterectomy, but they also face high risk of complications.
One of these complications is CHS, on which consensus regarding its definition is lacking. To facilitate future uniform investigations the following definition is proposed: headache, neurological deficit, and seizure or haemorrhage after cerebral revascularisation, typically ipsilateral to the treated artery
Search strategy and selection criteria
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