*7.8.3 Mechanism*

*New Insight into Cerebrovascular Diseases - An Updated Comprehensive Review*

scan is the most accessible and direct method to evaluate IAC in patients.

End-stage renal disease with long duration of hemodialysis [11–13].

IAC can lead to three significant hemodynamic effects: Firstly, it can lead to increase the arterial stiffness. This phenomenon is associated with aging and accelerated by other vascular risk factors. It can be measured by the pulse wave velocity (PWV) and may indicate early atherosclerotic changes. Several studies have verified the correlation between IAC and arterial stiffness, and this may increase the risk of stroke. Secondly, arterial stenosis can be linked to arterial calcification, which may lead to ischemic stroke due to direct luminal stenosis. Thirdly, IAC may lead to plaque stability. Intravascular ultrasound studies found heavily calcified plaques to be more resistant to plaque progression. Therefore, the findings for CAC suggest that substantial calcification may help stabilize atherosclerotic plaques. Also, a heavy plaque burden hidden in heavily calcified arteries may partially account for the association between severe arterial calcification and ischemic events regardless

Cerebral vasospasm is an essential source of morbidity and mortality in subarachnoid hemorrhage patients. Vasospasm is one of the most common acute complications. It can happen within 3–15 days with a peak incidence at 7 days after aneurysmal SAH. Symptomatic vasospasm occurs in 20–40% of subarachnoid hemorrhage cases and is considered as the least understood component in their care. The symptom severity depends upon the artery affected and the degree of collateral circulation. Strokes from vasospasm account for nearly 50% of the early deaths in patients who survive the initial subarachnoid hemorrhage treatment. It is characterized by a pathological; diffuse, affecting all layers of the involved arterial wall; and long-lasting narrowing of the lumen of the vessel of large-capacity cerebral arteries

The prevalence of intracranial artery calcification is:

Risk factors of intracranial artery calcification:

• Internal carotid artery: 60%

• Middle cerebral artery: 5%

History of cardiovascular disease.

*7.8.1 Hemodynamic and clinical effects of IAC*

*7.8.2 Vasospasm and delayed cerebral ischemia*

Excessive alcohol intake.

• Vertebral artery: 20%

• Basilar artery: 5%

Advanced age. Diabetes mellitus. Hypercholesterolemia.

Hypertension.

of plaque vulnerability.

to range from 60 to 90% according to ethnicity, age, and stroke or other risk factors. The vertebral artery is the second most common artery affected by calcification, while other arteries have been affected only by less than 5%. An unenhanced CT

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While the underlying mechanisms causing vasospasm are not fully understood, a proliferative inflammatory arteriopathy is the pathological feature of cerebral vasospasm. The intima shows disruption of the internal elastic lamina, and the media is thickened and fibrotic, with an increased smooth muscle cell proliferation. The adventitia is infiltrated with inflammatory cells, and the neuronal endings are impaired [14]. A significant predictor of vasospasm after SAH is the volume of blood present around the cerebral arteries of the circle of Willis which can be measured by transcranial Doppler (TCD), although it has been clearly demonstrated that prolonged exposure of cerebral arteries to perivascular blood is essential for the development of vasospasm. It is not possible to identify a single causative molecule as the culprit of vasospasm. However, vasospasm is believed to be produced by spasmogenic substances generated during the lysis of subarachnoid blood such as oxyhemoglobin (a product of auto-oxidation of hemoglobin), nitric oxide, and endothelin-1. Those agents may be contributors to the pathological event of vasospasm.

Oxyhemoglobin may directly or indirectly trigger arterial vasoconstriction.

Oxyhemoglobin can also exert a scavenging effect on nitric oxide. It has been demonstrated that nitric oxide (a potent vasodilator) depleted during vasospasm and can stimulate endothelial cells to produce endothelin-1.

Endothelin-1 is the most potent and long-lasting vasoconstrictor effect, which is also associated with morphological changes, mimicking the delayed cerebral vasospasm. It has been shown that endothelin-1 levels are increased, not only in the cerebrospinal fluid during SAH and severe neuronal injury due to vasospasm or bleeding event. Moreover, endothelin levels change in neurological symptoms, but they do not predict vasospasm as assessed by transcranial Doppler. These observations suggest that endothelin-1 acts as a marker of cerebral ischemic injury [15, 16].

#### *7.8.4 Diagnosis*

### *7.8.4.1 Transcranial Doppler*

It is a noninvasive tool and is useful for the detection and evaluation of vasospasm. It can be performed at the bedside.

It used as a screening tool in high-grade World Federation of Neurological Surgeons (WFNS) scale patients in whom a neurological examination cannot be readily followed to identify those at higher risk [17].

#### *New Insight into Cerebrovascular Diseases - An Updated Comprehensive Review*

It is a highly specific noninvasive exam but has a low level of sensitivity, and it is operator-patient dependent, and its value is debated.

In 2004, the American Academy of Neurology conducted a systematic review of the literature and concluded that TCDs could be used reliably to screen for the presence of vasospasm in the only MCA. Their criteria for the diagnosis or exclusion of vasospasm include flow velocity > 200 or 120 cm/s, respectively, significant increase in the flow velocities from day to day (>50 cm/s), and a Lindegaard ratio (MCAvelocity/ICAvelocity) > 6 [18].

#### *7.8.4.2 CT scan*

Noninvasive angiography with CT angiography (CTA) to confirm vasospasm for patients with elevated velocities on transcranial Doppler ultrasound. The plane CT scan is useful for ruling out other causes in the event of the occurrence of a deficit or worsening of the clinical state like rebleeding or ischemia. Several prospective cohorts showed a correlation between CTA and DSA in predicting vasospasm and that many unnecessary angiograms could be avoided by using CTA as a screening test [19, 20]. A recent meta-analysis found a sensitivity and specificity for CTA of 80 and 93%, respectively [21].
