*3.2.1.1 Cranial symptoms-involvement of intra carotid artery and vertebrobasilar branches*

Cranial symptoms are classically associated with GCA: new onset headaches, the most common initial symptom, typical in temporal area but can be diffuse/nonspecific, persistent throughout the day, partly responsive to analgesics; scalp tenderness seen in 50% of patients; usually noticed while brushing hair; temporal artery abnormalities pulse; jaw claudication is seen in 50% of patients, the most specific symptom of arteritis, is a mandibular pain brought on by speech and mastication, relieved when stopping the activities, highly suggestive of GCA, strongly associated with positive TAB. In rare cases, muscles of the tongue and swallowing may be affected.

### *3.2.1.2 Stroke in GCA*

Most strokes in the investigated GCA patients were found in the vertebrobasilar and internal carotid artery territory [33, 90]. The reported rate of stroke/transient ischemic attack (TIA) is approximately 5–20% [25, 33]. The underlying mechanism of cerebrovascular ischemia is related to the vascular dysfunction that is characteristic of GCA. More recent GCA studies [28, 33, 67] reported a 2.8% -7% incidence of ischemic stroke. As mentioned on previous section, a lot of inflammatory cells collect around internal elastic lamina but intracranial arteries lack an internal elastic lamina that being one of the reasons stroke is not seen as a severe manifestation of GCA in that territory.

In a cohort study evaluating the thrombotic risk in GCA patients vs. control it was found an increased risk of cerebrovascular accidents like in the other studies, and also peripheric arteritis and myocardial infarction [25]. The incidence rate ratio for CV events was 1.68 [25]. There is a significantly increased risk of thromboembolic disease in GCA during active disease; the risk for thrombotic events was reportedly the highest in the first month from the onset of the disease hazard ratio 4.92 (95% CI 2.59–9.34. The risk for CV risk was much decreased at a follow-up (hazard ratio of 1.70) (95% CI 1.51–1.91) [25]. Although patients with GCA have an increased risk of cerebrovascular accidents, long-term survival study concluded that GCA patients' mortality is not higher than in the general population if treated properly [34].

*Cellular and Molecular Characteristics of Vascular Damage in Giant Cell Arteritis, the 'Unmet… DOI: http://dx.doi.org/10.5772/intechopen.97933*

#### *3.2.1.3 Visual symptoms-internal carotid artery branches involvement*

Blindness is the most severe thromboembolic event experienced by 15–20% of GCA patients, usually at onset [6, 27]. It is rarely reversible. Visual loss is abrupt and painless and the most feared consequence of GCA by the clinicians. GCA is an ophthalmology emergency which requires 'emergency' IV pulse therapy with high dose prednisolone followed by oral therapy to prevent progression in the affected eye and extension to the contralateral eye [21].

Transient monocular visual loss (TMVL) or amaurosis fugax means a person cannot see through one or both eyes, a symptom of poor blood supply to the eye(s). TMVL is seen in 10–15% of patients. If left untreated 50% of cases are rapidly progressing to permanent visual loss (VL). Unilateral VL is a strong risk factor for VL in the contralateral eye which can occur in more than 50% of cases within 2 weeks if left untreated [27].

VL is usually due to arteritic anterior ischemic optic neuropathy: occlusive arteritis of the posterior ciliary branches of the ophthalmic artery which are the main arterial supply of the optic nerve [91]; it accounts for 85% of all VL cases in GCA [27, 91]. VL can also be due to central retinal artery occlusion or posterior ischemic optic neuropathy [27, 33, 91]. Other ocular symptoms in GCA might be ophthalmoplegia and diplopia from ischemia of the extraocular muscles and blurry vision [27].

Intriguingly, one of the acute phase reactants, an innate immunity pattern recognition receptor, pentraxin 3(PTX3) accumulates at the site of active vascular remodeling, more so in GCA patients with recent ocular ischemic events ischemia [52], indicative of thrombo-inflammation manifestations in GCA vessels that supply the eye, as shown by immunohistochemistry and measurement of plasma levels of PTX3 [52].

#### *3.2.1.4 Extracranial/large vessel involvement*

Extracranial/large vessel involvement refers to involvement of aorta and its major branch vessels. About 25–30% of GCA cases have clinically evident large vessel involvement [90] but PET scans and CT angiography have demonstrated that subclinical large vessel involvement is present in a significant percentage of cases [90]. The GCA vasculopathy may evolve to aneurysm formation and vascular rupture of aorta and stenosis/occlusion of its branch vessels [68]. Clinically, these patients may present extremity claudication, absent peripheral pulses, abdominal pain, masked HTA, dizziness depending on affected vessels. Because of risk of vascular stenosis, it is needed an evaluation of the blood supply. If decreased blood supply is found, the question is if this is part of GCA occlusive complications or related to artherosclerosis which is almost universal in people in this age group that develop GCA or both. Leg vessels are less involved in GCA than the arm, the neck, the brain, or the eye vessels, but vascular complications can occur in the leg too, just less frequently. Blood pressure and pulses discrepancies of 15-20 mg between left and right extremities might raises question of large vessel arteritis involvement and might hide hypertension.

#### *3.2.2 Venous thrombotic complications in GCA*

In a cohort study of circa one thousand GCA patients, an increased risk of venous thromboembolism was observed (both DVT and pulmonary embolism), during the early active, uncontrolled phase of the disease [66].

Nevertheless, with appropriate health care, giant cell arteritis has a relatively good prognosis.
