ABSTRACT
Background
In patients with giant cell arteritis (GCA), 2.8%–8.2% present with ischemic stroke (IS) or transient ischemic attack (TIA). GCA diagnosis may be overlooked, and immunosuppressive treatment delayed if typical symptoms are absent or if a common cause of IS coexists. This study aimed to identify potential markers of GCA through clinical evaluation and baseline investigation of IS/TIA patients.
Methods
Two authors independently conducted a scoping review using MEDLINE and EMBASE databases to identify patients diagnosed with GCA after presenting with IS/TIA. All articles, including the gray literature, were considered from January 2000 onwards if individualized data were described. Only cases of IS/TIA with GCA later diagnosed as the etiology were included for analysis.
Results
A total of 101 publications were included, pooling data on 141 patients for analysis. The mean age was 73.6 years, and 61 were women. Patients experienced either single (56.0%) or multiple IS/TIA events (44.0%). Associated symptoms included GCA‐related pain, such as headaches (50.4%), constitutional symptoms (47.5%), and temporal artery inflammation (27.0%). Neurological deficits involved corticospinal tracts (41.8%), and cerebellar functions (53.2%). Most patients had clinical or radiological evidence of vertebrobasilar involvement (83.7%). Multifocal involvement of the vertebrobasilar and carotid territories was supported when combining clinical‐radiological manifestations (41.1%). Recurrent events were common (44.0%).
Conclusion
GCA should be considered in IS/TIA patients aged ≥ 50 years with vertebrobasilar or multiterritorial involvement, or recurrent IS/TIA despite secondary prevention.
Keywords: etiology, giant cell arteritis, ischemic attack, ischemic stroke, transient, vasculitis
Giant cell arteritis should be considered in patients aged ≥ 50 years presenting with vertebrobasilar ischemic events, multifocal infarcts affecting both vertebrobasilar and carotid territories, or recurrent ischemic events despite optimal secondary prevention. Neuroimaging findings such as lesions centered on the distal extradural segments of the vertebral and internal carotid arteries without significant intracranial extension, bilateral vertebral artery occlusion, and middle cerebellar peduncle watershed infarcts strongly suggest giant cell arteritis.
1. Introduction
Giant cell arteritis (GCA) is the most common systemic autoimmune vasculitis in adults. Mainly found in people aged over 50, GCA lifetime risk reaches 0.5% in men and 1% in women [1]. Medium and large vessels are affected, mostly the aorta and its branches. Classic clinical manifestations include constitutional symptoms, headache, jaw claudication, and signs of temporal artery inflammation. Ocular‐orbital ischemia threatens vision with 8.2%–18.4% of patients with GCA presenting with permanent monocular or binocular visual loss primarily due to ischemic optic neuropathy, unheralded by classic GCA manifestations in 20% of cases [2, 3]. Brain ischemia is rare, with 2.8%–8.2% of patients with GCA experiencing ischemic stroke (IS) at presentation or shortly after [4, 5, 6]. GCA diagnosis may be missed in patients presenting with IS or transient ischemic attack (TIA) if classic manifestations are lacking or overlooked, or if vasculitic imaging findings are misinterpreted as atherosclerosis [7]. Further increasing the diagnostic challenge, IS/TIA investigations do not routinely include inflammation markers such as the C‐reactive protein, and diagnostic GCA tests. Timely diagnosis and treatment may prevent acute ischemic events and long‐term vascular complications [8]. Therefore, it is important to recognize GCA in patients presenting with IS/TIA.
There is limited literature on GCA presenting with IS/TIA, with existing studies being predominantly retrospective or consisting of small or MRI‐proven case series [9, 10, 11, 12]. Our scoping review aims to identify GCA characteristics (clinical manifestations and baseline investigation results) in individuals presenting with IS/TIA.
2. Methods
Our study was conducted and our results reported according to the PRISMA extension for Scoping Reviews statement (PRISMA‐ScR) [13].
Patient population: Eligible patients had at least one episode of acute IS/TIA, with GCA subsequently diagnosed and established as the etiology. IS/TIA were defined as focal neurological deficits of sudden onset, attributed to brain ischemia. IS deficits were persistent or associated with relevant recent brain infarcts on imaging. Patients with focal neurological deficits reported as progressive were also eligible if brain imaging documented relevant infarcts. TIA deficits were short‐lasting and unassociated with relevant brain infarcts. Acute ocular‐orbital (i.e., pre‐chiasmatic) ischemia was considered apart from IS/TIA, including amaurosis fugax, ischemic optic neuropathy, retinal infarct, and ophthalmoparesis. Cases of isolated acute ocular‐orbital ischemia (no IS/TIA) were not eligible.
GCA diagnosis was established from the most recent American College of Rheumatology/EULAR criteria at the time of case publication. These criteria were revised in 2022 and include clinical criteria, halo sign on temporal artery ultrasound, positive temporal artery biopsy, or abnormal fluorodeoxyglucose uptake on positron emission tomography (PET) [14]. GCA diagnosis was also eligible from autopsy, or as reported by the authors. Presumed diagnoses were not eligible.
2.1. Literature Search Strategy
Supporting Information describes the complete search strategy undertaken by two authors without length, setting, or language restrictions. The search strategy was completed independently by two authors (A.‐V.M. and J.‐P.M.) on January 12, 2023. First, a comprehensive MEDLINE and EMBASE database search was conducted using keywords related to GCA and IS/TIA, with date restriction from January 2000 onwards. Gray literature found on EMBASE was assessed and considered. Results were compiled, deduplicated, and imported into EndNote 20. A single author later repeated the search strategy and screening process on April 21, 2024 to update the review with the most recent articles.
2.2. Record Selection
All articles underwent screening based on title and abstract, with reasons for rejection documented. The article lists from the two independent search strategies were compared. Duplicates were removed, retaining only the most complete and recent publications.
2.3. Data Collection
The remaining articles were added to a standardized Excel sheet and underwent a first full review by two authors (A.‐M.V. and M.P.‐C.). A second full review was conducted by a senior author to ensure consistency (S.L.). Predetermined definitions and case report forms were systematically used to collect data on patient demographics, past medical history, clinical manifestations, investigation results using original laboratory units, follow‐up, and outcomes. Undefined variables from the source articles were presumed to be consistent with our study definitions. Unreported data and investigations were considered absent. Clinical manifestations and investigation results were those that preceded GCA diagnosis or treatment, whichever came first. Clinical manifestations were classified into constitutional symptoms, GCA‐related pain, temporal artery inflammation signs, ocular‐orbital ischemia, and IS/TIA deficits. Data collected by each author were compared. Discrepancies were resolved through discussion, with a third author consulted in cases of unresolved conflicts. Data from individual studies were compiled into an Excel file.
One author (S.L.) grouped IS/TIA deficits by functional categories and symptomatic cerebrovascular territories (right carotid artery, left carotid artery, vertebrobasilar system). Multiple functional categories were identified when deficits did not fit just one. After functional classification, the remaining symptoms were labeled as unclassifiable. The left hemisphere was presumed dominant unless specified. Multiterritorial neurological involvement was identified only when all IS/TIA deficits were inconsistent with a single vascular territory. The number of IS/TIA episodes before GCA diagnosis or treatment was recorded. IS/TIA deficits corresponding to a single vascular territory were considered synchronous unless otherwise specified, indicating a single cerebrovascular event. Progressive deficits in a single vascular territory were considered recurrent events.
Recent infarcts identified on brain CT or MRI, whether symptomatic or not, were attributed to GCA and categorized by cerebrovascular territories. Chronic brain infarcts were excluded from analysis. IS/TIA deficits and recent brain infarcts in the posterior cerebral artery territory were attributed to the vertebrobasilar system unless an ipsilateral fetal origin was reported. Bilateral anterior cerebral artery deficits or infarcts were considered multiterritorial unless an unpaired azygos artery was described.
We analyzed supra‐aortic artery stenoses and occlusions documented on baseline Doppler ultrasound, CT angiography, or magnetic resonance angiography. We did not analyze vascular changes identified from imaging studies conducted to confirm GCA diagnosis. These included vessel wall edema (Doppler halo sign), gadolinium enhancement on vessel wall MRI, and hypermetabolism on PET. Artery stenoses/occlusions were categorized by cerebrovascular territories. We distinguished extradural and intradural involvement of the vertebral and internal carotid arteries (ICA). Both segments were considered affected when “distal” vertebral and ICA involvement was not further described in the original manuscript.
Erythrocyte sedimentation rate ≥ 50 mm/h (Westergren method) and C‐reactive protein levels ≥ 10 mg/L were considered increased [14].
We recorded the time relationship between the onset of GCA‐related pain or constitutional symptoms, orbital–ocular manifestations, IS/TIA, first medical evaluation, GCA diagnosis, and immunosuppressant treatment. We also recorded follow‐up duration and outcomes from GCA diagnosis or treatment. Outcome events during follow‐up included subsequent IS/TIA, ocular–orbital ischemia, and death.
2.4. Data Analysis
Biochemical data were standardized to the international unit system when reported otherwise. All data were processed using R‐Studio to generate clinical descriptive statistics. Dichotomous variables were summarized as percentages, while continuous variables were reported as means with standard deviations or medians with interquartile ranges, as appropriate.
3. Results
3.1. Literature Search
The search strategy identified 6800 records, of which 5054 duplicates were removed. The remaining 1746 records underwent title and abstract screening, followed by full‐text review of 169 articles, resulting in the inclusion of 101 articles. A total of 141 patients were pooled for analysis. Figure 1 shows the scoping review flowchart.
FIGURE 1.
Scoping review flowchart. GCA, giant cell arteritis; TIA, transient ischemic attack.
3.2. Study Patients
Table 1 summarizes the demographics, past medical history, and antithrombotic treatment of the 141 included cases. Out of 138 patients who disclosed sex, 77 (54.6%) were men (men‐to‐female ratio: 1.26:1). Mean age (73.6 ± 9.2 years) was similar between sexes. Median age was 75 years. Modifiable risk factors were reported in most patients (62.4%), with hypertension being the commonest (48.2%). Eight patients (5.7%) previously had symptomatic atherosclerosis. Ten patients (7.1%) had an atrial arrhythmia. Two patients had remote TIA unrelated to GCA, respectively 8 and ≥ 20 years before presentation. None had remote IS.
TABLE 1.
Demographics, past medical history, and antithrombotic treatment of 141 patients presenting with ischemic stroke or TIA in the setting of GCA.
| Sex, n (%) | |
| Women | 61 (43.3%) |
| Men | 77 (54.6%) |
| Sex unreported | 3 (2.1%) |
| Mean age ± standard deviation (years) | |
| Women | 73.3 ± 7.8 |
| Men | 73.6 ± 10.2 |
| Sex unreported | 77.7 ± 10.6 |
| Modifiable risk factors, n (%) | |
| Arterial hypertension | 68 (48.2%) |
| Dyslipidemia | 32 (22.7%) |
| Diabetes | 22 (15.6%) |
| Active smoking | 17 (12.1%) |
| None reported | 53 (37.6%) |
| Symptomatic atherosclerosis, n (%) | |
| Coronary arteries | 7 (5.0%) |
| Carotid arteries | 1 (0.7%) |
| Other arteries | 2 (1.4%) |
| None reported | 133 (94.3%) |
| Atrial arrhythmia, n (%) | |
| Atrial fibrillation | 7 (5.0%) |
| Atrial flutter | 2 (1.4%) |
| Sick sinus syndrome | 1 (0.7%) |
| None reported | 131 (92.9%) |
| Remote brain ischemic events | |
| Transient ischemic attack | 2 (1.4%) |
| None reported | 139 (98.6%) |
| Antithrombotic treatment | |
| Antiplatelets | 7 (5.0%) |
| Anticoagulants | 6 (4.3%) |
| None reported | 129 (91.5%) |
Abbreviations: GCA, giant cell arteritis; TIA, transient ischemic attack.
3.3. GCA‐Related and IS/TIA Clinical Manifestations
Table 2 describes the clinical manifestations at GCA diagnosis or treatment initiation. Most patients (n = 113; 80.1%) had one or more GCA manifestations other than IS/TIA. These were constitutional symptoms (47.5%), GCA‐related pain (66.7%, mostly headaches), evidence of temporal artery inflammation (27.0%), and ocular‐orbital ischemia (15.6%). Among functional categories of IS/TIA deficits, cerebellar manifestations predominated (53.2%), followed by corticospinal (41.8%), cognitive (33.3%), oculovisual (32.6%), other cranial nerve (14.2%), and somatosensory involvement (9.2%). Fifteen patients presented with deficits that could not be classified, in addition (8.5%) or not (2.1%) with deficits from other functional categories. Unclassifiable deficits were dysarthria (n = 3), bradykinesia (n = 2), mobility decline (n = 1), motionless state (n = 1), dizziness (n = 2), unsteady gait (n = 2), falls (n = 2), tremor (n = 1), nycturia (n = 1), hemodynamic instability (n = 1), and central hyperventilation (n = 1). Functional classification was impossible in six additional patients (4.3%) reported with IS/TIA (n = 4) or Wallenberg syndrome not further described (n = 2).
TABLE 2.
Clinical manifestations of GCA and IS/TIA of 141 patients presenting with inaugural stroke or TIA in the setting of GCA.
| Constitutional symptoms, n (%) | |
| Fever | 18 (12.8%) |
| Nocturnal sweats | 2 (1.4%) |
| Fatigue | 23 (16.3%) |
| Weight loss | 37 (26.2%) |
| Others | 23 (16.3%) |
| Absent or unreported | 74 (52.5%) |
| GCA‐related pain, n (%) | |
| New‐onset headache | 71 (50.4%) |
| Scalpalgia | 8 (5.7%) |
| Jaw claudication | 30 (21.3%) |
| Polymyalgia rheumatica (neck or shoulder pain or stiffness) | 34 (24.1%) |
| Absent or unreported | 47 (33.3%) |
| Temporal artery inflammation, n (%) | |
| Tenderness | 14 (9.9%) |
| Pulselessness | 21 (14.9%) |
| Induration | 7 (5.0%) |
| Thickening | 19 (13.5%) |
| Others abnormalities | 3 (2.1%) |
| Absent or unreported | 103 (73.0%) |
| Ocular‐orbital ischemia, n (%) | |
| Present | 22 (15.6%) |
| Absent or unreported | 119 (84.4%) |
| IS/TIA deficits by functional category, n (%) | |
| Cognitive impairment | |
| Altered consciousness | 19 (13.5%) |
| Aphasia | 13 (9.2%) |
| Others | 27 (19.1%) |
| Absent or unreported | 94 (66.7%) |
| Oculovisual impairment | |
| Retrochiasmatic visual field defect | 13 (9.2%) |
| Blurry vision NOS | 14 (9.9%) |
| Oculomotor paresis or diplopia NOS | 25 (17.7%) |
| Pupillary defect | 3 (2.1%) |
| Absent or unreported | 95 (67.4%) |
| Other cranial nerves | |
| Present | 20 (14.2%) |
| Absent or unreported | 121 (85.8%) |
| Corticospinal tract | |
| Present | 59 (41.8%) |
| Absent or unreported | 82 (58.1%) |
| Somatosensory system | |
| Present | 13 (9.2%) |
| Absent or unreported | 128 (90.8%) |
| Cerebellum | |
| Nystagmus | 15 (10.6%) |
| Vertigo | 33 (23.4%) |
| Dysarthria | 27 (19.1%) |
| Gait ataxia | 49 (34.8%) |
| Dysmetria | 28 (19.9%) |
| Others | 17 (12.1%) |
| Absent or unreported | 66 (46.8%) |
| Unclassified manifestations | |
| Combined with classified deficits | 12 (8.5%) |
| Unassociated with classified deficits | 3 (2.1%) |
| IS/TIA not further described | 4 (2.8%) |
| Wallenberg syndrome | 2 (1.4%) |
Abbreviations: GCA, giant cell arteritis; IS, ischemic stroke; NOS, not otherwise specified; TIA, transient ischemic attack.
3.4. Number of IS/TIA Episodes at GCA Diagnosis or Treatment
The median interval from the onset of any GCA‐related symptoms to GCA diagnosis or treatment was 2.2 months (interquartile range: 0.8–4.0 months). During this interval, most patients (56.0%) had experienced a single episode of IS (n = 74) or TIA (n = 5). Among patients with multiple episodes (44.0%), most had a combination of IS and TIA (n = 60) with progressive deficits in about one‐fourth of them. Only two patients had multiple TIAs and no IS. Hemodynamic and vaso‐occlusive IS/TIA mechanisms could not be differentiated in most cases. The proportion of patients without GCA manifestations other than IS/TIA was similar in those with single (n = 17; 21.5%) and multiple episodes (n = 11; 17.7%).
3.5. Cerebrovascular Territories
Table 3 shows clinical or radiological manifestations by cerebrovascular territories at GCA diagnosis or treatment. Whether vascular changes resulted from vasculitis, arteriosclerosis, or another artery disease was not specified for most patients. Most patients (58.9%) had single‐territory involvement. Multiterritorial IS/TIA deficits (3.5%) and bilateral ocular‐orbital ischemia (2.1%) were rarer than a combination of IS/TIA deficits and ocular‐orbital ischemia in different territories (12.8%). Most radiological studies identified recent brain infarcts in different territories (16.4%) and vascular stenosis or occlusion involving multiple territories (30.7%). These included lesions in clinically silent territories. Multiterritorial involvement (41.1%) and vertebrobasilar involvement (83.7%) stood out when considering all clinical and radiological data. Unusual infarct locations were described (5.7%), including bilateral (n = 3) or unilateral middle cerebellar peduncle (MCP) (n = 3), bilateral dentate nucleus (n = 1), and anterior genu fornices (n = 1).
TABLE 3.
Cerebrovascular territories with GCA manifestations as identified from clinical and radiological manifestations of 141 patients presenting with inaugural stroke or TIA in the setting of GCA.
| Cerebrovascular territory | IS/TIA deficits (n = 141) | Ocular‐orbital ischemia (n = 141) | Recent brain infarcts (n = 134) a | Artery stenosis or occlusion (n = 127) b | Total (n = 141) |
|---|---|---|---|---|---|
| Right carotid artery | 4 (2.8%) | 9 (6.4%) | 22 (16.4%) | 34 (26.8%) | 44 (31.2%) |
| Left carotid artery | 18 (12.8%) | 9 (6.4%) | 25 (18.7%) | 44 (34.6%) | 57 (40.4%) |
| Vertebrobasilar system | 95 (67.4%) | NA | 104 (77.6%) | 89 (70.1%) | 118 (83.7%) |
| Single territory | 107 (75.9%) | 12 (8.5%) | 105 (78.4%) | 68 (53.5%) | 83 (58.9%) |
| Multiple territories | 5 (3.5%) | 3 (2.1%) | 22 (16.4%) | 39 (30.7%) | 58 (41.1%) |
| None | NA | 119 (84.4%) | 6 (4.5%) c | 20 (15.7%) d | NA |
| Unlocalizable | 29 (20.6%) | 8 (5.7%) | 2 (1.5%) | 0 | 2 (1.4%) |
Abbreviations: GCA, giant cell arteritis; IS, ischemic stroke; NOS, not otherwise specified; TIA, transient ischemic attack.
Excluding 3 TIA patients and 4 patients with brain imaging not reported.
Excluding 14 patients with vascular imaging not reported.
2 patients investigated only by CT and 2 had no recent changes on MRI.
10 patients imaged only by Doppler.
3.6. Potential Markers of GCA in Patients With IS/TIA
Most patients had clinical or radiological evidence of vertebrobasilar involvement (83.7%). Other common features included recurrent IS/TIA at GCA diagnosis or treatment (44.0%), multiterritorial involvement (41.1%), and GCA‐related clinical manifestations other than IS/TIA (80.1%). The latter included constitutional symptoms (47.5%), GCA‐related pain (66.7%), signs of temporal artery inflammation (27.0%), and ocular‐orbital ischemia (15.6%). At least one of these markers was present in all study patients.
Table 4 and Figure 2 compare GCA symptoms in patients with single‐territory versus multiterritorial involvement. Seventeen of 83 patients (20.5%) with single‐territory involvement had no constitutional symptoms, GCA‐related pain, signs of temporal artery inflammation, or ocular‐orbital ischemia. All of them had vertebrobasilar involvement, five had experienced multiple IS/TIA at GCA diagnosis or treatment, and three had brain imaging showing unusual infarct location.
TABLE 4.
Typical GCA symptoms in patients with single‐territory and multiterritorial involvement.
| Single‐territory involvement (n = 83) | Multiterritorial involvement (n = 58) | |
|---|---|---|
| Constitutional symptoms | 42 (50.6%) | 25 (43.1%) |
| GCA‐related pain | 54 (65.1%) | 40 (69.0%) |
| Temporal artery inflammation | 22 (26.5%) | 16 (27.6%) |
| None | 17 (20.5%) | 11 (19.0%) |
Abbreviations: GCA, giant cell arteritis; IS, ischemic stroke; TIA, transient ischemic attack.
FIGURE 2.
Venn diagrams of IS/TIA patients presenting with non‐neurological symptoms as previously classified (including GCA‐related pain, temporal artery inflammation, and constitutional symptoms) for single‐territory (A) and multiterritorial (B) involvement, with 17 and 11 patients having only neurological symptoms, respectively. GCA, giant cell arteritis; IS, ischemic stroke; TIA, transient ischemic attack.
Most tested patients had an increased erythrocyte sedimentation rate (89/118; 75.4%) or C‐reactive protein level (84/97; 86.6%). Both test results were normal in a minority (5/85; 5.9%) or not reported in 11/141 (7.8%).
3.7. GCA Confirmation
GCA diagnosis was confirmed by temporal artery biopsy (77.3%), temporal artery ultrasound (29.8%), fluorodeoxyglucose‐PET (16.3%), or autopsy (5.7%). Only seven patients were diagnosed using the American College of Rheumatology/EULAR clinical criteria only (n = 6; 4.3%) or as reported by the authors (n = 1; 0.7%).
3.8. Clinical Outcomes
Death occurred in 31/106 patients with reported follow‐up. Four died within 10 days of single IS presentations. Three patients died of aspiration pneumonia following initial IS. Five more patients died from recurrent IS, and one from acute myocardial infarction in the first month after treatment initiation. Among patients on immunosuppressants for 1 to 8 months, reported causes of death were recurrent IS (n = 10), neurological complications (n = 1), IS disabilities (n = 1), pneumonia (n = 2), and sepsis (n = 2). Two patients died of cancer 9 and 46 months following the inaugural IS, and one from heart failure at 90 months. Information surrounding death was lacking in one patient.
Median follow‐up among the survivors was 6 months [interquartile range 2–18 months]. Eighteen patients experienced ≥ 1 non‐fatal recurrent IS/TIA despite immunosuppressant treatment. One of these patients had a central retinal artery occlusion. Two additional patients received immunosuppressant treatment for only a short duration and subsequently suffered recurrent IS at 4–6 months.
4. Discussion
Our study identified several potential GCA characteristics among clinical features and baseline investigation results of 141 IS/TIA patients with GCA subsequently diagnosed and established as the etiology. All study patients had at least one of these GCA markers, which may help differentiate GCA from other causes of IS/TIA and allow for timely diagnosis and treatment.
Vertebrobasilar deficit is the most common clinical marker of GCA (67.4%). Cerebellar deficits prevail (53.2%). A review of brain MRI‐confirmed GCA‐related strokes found vertebrobasilar infarcts in 62.6% and ICA infarcts in 48.0% [12]. Combining clinical deficits with ischemic lesions on imaging, vertebrobasilar involvement was found in 83.7% of cases. These proportions are greater than generally reported in small‐sized series with cerebellar deficits in 31.6%–50.0% and vertebrobasilar clinico‐radiological localization in 42.9%–87.5% [4, 9, 10, 11, 15]. Vertebrobasilar involvement in GCA‐related IS/TIA is threefold that reported in all‐cause IS (27%) [16, 17]. Consequently, GCA is estimated to make up only 0.2%–0.4% of all‐cause IS, about 3.1% of all‐cause vertebrobasilar IS, and 7.4% of IS with bilateral vertebral artery occlusion [18, 19, 20, 21].
Hemodynamic impairment downstream of focal arterial stenosis appears to be the main IS mechanism in GCA. Recent ischemic lesions in watershed areas were documented by MRI in 88.9% of ICA infarcts and possibly 61.7% of vertebrobasilar infarcts [12]. GCA‐related IS/TIA's propensity for the posterior circulation may be due to the smaller diameter of vertebral arteries (3.0–3.2 mm) compared to ICA (4.7–4.8 mm), and their earlier hemodynamic involvement when bilaterally affected, or insufficiently compensated by the circle of Willis or the contralateral circulation [22, 23]. In 6/103 (5.8%) of our study patients with vertebrobasilar infarct documented by brain imaging, the lesion was limited exclusively to one or both MCP, which can be considered a watershed region between the anteroinferior and superior cerebellar arteries. In a review of published cases of GCA‐related stroke confirmed by MRI, vertebrobasilar infarcts involved the MCP in 25.5% and were limited to this structure in 6.4% [12]. Because isolated MCP infarcts account for ≤ 0.26% of all‐cause IS, this unusual infarct location strongly suggests GCA [24]. Bilateral dentate nucleus and anterior genu fornices were other unusual infarct locations in our study.
Multivascular involvement is a hallmark of vasculitis, including GCA. Whereas only 3.5% of patients with GCA have multiterritorial IS/TIA deficits, brain CT or MRI documents recent multiterritorial infarcts in 16.4%. A previous MRI study found infarcts in both the anterior and posterior territories in 11% [12]. Anterior circulation infarcts were bilateral in 52.8%. Multiterritorial involvement reaches 41.1% if IS/TIA deficits, ocular‐orbital ischemia, recent brain infarcts, and vascular stenosis are considered together.
GCA typically affects extracranial arteries, with intracranial extension not beyond the proximal intradural segment of the vertebral and ICA, reflecting the distribution of elastin fibers as antigenic targets [7, 25, 26, 27]. Involvement by GCA of other intracranial arteries is rare [28]. Necropsy‐proven cases are exceptional, with only two patients in our study group [5, 29, 30]. Four other study patients had vasculitic extension to intracranial arteries evidenced by gadolinium enhancement at magnetic resonance angiography (n = 3), halo sign at Doppler ultrasound (n = 1) [19, 31, 32, 33]. Reversibility of artery stenosis following treatment may support GCA [34]. A study reported stenosis or occlusion of the middle or anterior cerebral arteries in 6.1% of ICA infarcts, and basilar stenosis or occlusion in 23.5% of vertebrobasilar infarcts [12]. However, intracranial artery stenosis or occlusion is nonspecific and may result in most patients with GCA from coexistent atherosclerosis and other arterial diseases.
Unlike CGA, primary angiitis of the central nervous system (CNS) and amyloid‐β‐related arteritis are limited to the CNS arteries. Varicella zoster virus (VZV) vasculopathy is another form of CNS vasculitis [35]. Its diagnosis is established by CNS biopsy showing viral infiltration and histoarchitectural destruction of the vessel wall, or by analysis of the cerebrospinal fluid revealing VZV antigens or anti‐VZV immunoglobulin G [35]. Controversial data suggest that GCA may be another form of vasculitis caused by VZV. In one study, VZV antigens were detected in 73% of temporal artery biopsy samples consistent with a diagnosis of GCA (combined with VZV DNA in 40% of these cases), in 64% of negative biopsy specimens from patients with a clinical diagnosis of GCA, and in 20% of normal temporal arteries [36]. However, other authors have reported VZV antigens in lower proportions among biopsy specimens confirming GCA, and false‐positive staining for VZV antigens due to antibody cross‐reactivity [37]. Furthermore, VZV reactivation may result from the inflammatory process of GCA rather than being the cause. Finally, the hypothesis that VZV is the causative agent does not explain why GCA mainly affects elastic arteries.
Constitutional symptoms, GCA‐related pain, ocular‐orbital ischemia, or signs of temporal artery inflammation precede GCA diagnosis or treatment in most IS/TIA patients (81.6% of our study group). Our findings are consistent with previous studies, including small‐sized IS/TIA cohorts [4, 9, 10, 15, 32, 38]. Together, these manifestations were equally common between single and multiple IS/TIA patients, indicating their role as a potential GCA marker in both groups. Constitutional symptoms and pain do not herald the usual IS/TIA etiologies and should raise suspicion of an unusual cause, including GCA. Potential pitfalls include misattributing headaches and neck pain to cervical spine degeneration, other common causes in the GCA age group, or IS itself, which occurs in 7%–28% unselectively [39, 40, 41]. Their recent onset before IS/TIA is a clue that should not be overlooked. In return, one‐fifth of our study patients had no GCA‐related clinical manifestations other than IS/TIA. Likewise, 20% of patients with GCA presenting with visual loss have none of the classic clinical manifestations of GCA [3, 4]. Inflammation (constitutional symptoms and pain) and ischemia (jaw claudication, ocular‐orbital ischemia, and IS/TIA) represent different non‐exclusive features of GCA diagnosis. Patients with GCA without inflammatory manifestations are more likely to suffer visual loss or IS/TIA [42]. It is possible that this group seeks less medical attention and could not benefit from immunosuppressant treatment before experiencing ischemic complications. Ischemic visual loss predicts IS in patients with GCA and should always raise doubts about GCA [4]. This remains true in IS/TIA patients aged ≥ 50, especially with vertebrobasilar or contralateral ICA involvement. Finally, clinical evidence of temporal artery inflammation was reported in only one‐fourth of our cases. Smaller‐sized studies reported variable proportions (0%–75%) [4, 9, 38]. Signs of temporal artery inflammation may suggest GCA and may be easily missed if their careful evaluation is not part of routine IS examination.
Within a 2.2‐month median interval from GCA symptom onset to diagnosis or treatment, 44% of patients had multiple IS/TIA episodes. This risk is considerably greater than the 1‐year IS risk of 4.7% for all‐cause hemorrhagic or IS [43]. Many GCA‐related IS/TIA may recur despite antithrombotic treatment due to hemodynamic impairment associated with severe artery stenosis. Early and unexplained IS/TIA recurrence should raise doubts about a possible GCA diagnosis.
GCA causes less than 1% of IS [44]. Common causes may therefore mask the diagnosis. As expected for the GCA age group, 7.1% of our study patients had atrial arrhythmia. Atrial fibrillation and other cardioembolic sources account for one‐fourth of IS and are the main cause of multiterritorial brain infarcts [45]. Contrasting with GCA, cardioembolic infarcts are not associated with cervical artery stenosis and are preferentially lobar rather than watershed [46, 47]. Asymptomatic atherosclerosis is highly prevalent, causing one‐third of IS [48]. Atherosclerosis involves the aorta and supra‐aortic sites of flow turbulence. Despite possible overlaps, GCA stenoses are centered on the ICA cavernous, clinoid, and supraclinoid segments and the vertebral artery third and fourth segments. GCA stenoses end soon after these arteries pierce the dura, sparing other intracranial arteries [12, 49, 50]. Conversely, atherosclerosis may involve the vertebral artery segment distal to the posteroinferior cerebellar arteries, the basilar trunk, and the main cerebral arteries [21]. GCA stenoses are often severe, concentric, fusiform, multisegmental, and multivascular [20, 50].
Our review of published case reports has potential limitations. External case adjudication was impossible. Nevertheless, using strict inclusion criteria, we ascertained proper GCA diagnosis. The validity of our findings is supported by the epidemiological data, which fall within the midrange of estimates reported in previous smaller studies. Whereas women account for 67.6% of unselected patients with GCA, we found more men presenting with IS (sex ratio: 1.26) [14]. Previous studies reported sex ratios from 0.73 to 1.57 [9, 10, 11, 12]. Median (75 years) and mean age (73.6 ± 9.2 years) of our study group compare with previous studies (median: 72–83 and mean: 76.2 ± 5.3 years) [9, 10, 11, 12]. Younger age was reported for patients with GCA with carotid artery stenosis and IS (mean 68.2; median 69 years) [49]. Because the reviewed publications used variable definitions and descriptions, the number of clinical and investigation variables we could assess was limited and presumptions were made. We therefore regrouped IS/TIA manifestations by functional categories and cerebrovascular territories following a usual neurovascular approach. Despite potential underreporting, we identified several GCA markers consistent with most previous smaller‐sized case series.
4.1. Case Report
A 70‐year‐old man was brought to our hospital with sudden right‐sided palsy. He reported no previous symptoms. Brain CT was unremarkable. CT angiography revealed typical atherosclerotic changes located at the aortic arch and carotid bifurcations, irregular proximal vertebral arteries, as well as bilateral stenoses affecting the ophthalmic, clinoid, and supraclinoid segments of the carotid arteries and the distal part of the vertebral arteries (Figure 3A). The basilar and cerebral arteries were notably spared. There was no large vessel occlusion. He received thrombolytic therapy for acute IS, presumed to result from atherosclerosis. Brain MRI subsequently confirmed an acute left‐sided infarction of the floor of the 4th ventricle (Figure 4A). Over the next 3 months, the patient developed new bilateral shoulder pain. Despite antiplatelet agents and optimal treatment of atherosclerotic risk factors, he suffered multiple recurrent IS/TIA. Acute brain infarctions were confirmed by MRI in the vertebrobasilar and left carotid territories, including both MCPs, the left midbrain, and the left caudate nucleus (Figure 4B). Repeat CT angiography documented progression of concentric stenoses, which remained maximal in the distal segments of the carotid and vertebral arteries, with evidence of vessel wall thickening (Figure 3B). C‐reactive protein levels were measured at 13–35 mg/L. Ultrasound of the temporal arteries showed a bilateral halo sign. GCA was diagnosed, and immunosuppressive treatment was initiated 3 months after his first IS. The patient died 2 weeks later. This IS patient, not previously reported in the literature, had several of the GCA markers identified in our study.
FIGURE 3.
Computed tomography angiography: Irregular vertebral arteries, with proximal right V3 stenosis at stroke presentation (A). Radiological deterioration 3 months following presentation, with diffuse concentric narrowing, and more severe right V3 stenoses (B). V1, V2, and V3: First, second, and third segments of the vertebral arteries.
FIGURE 4.
Brain diffusion weighted magnetic resonance imaging: Acute left pontine infarct at stroke presentation (A). New acute infarcts 3 months following presentation, involving both middle cerebellar peduncles, the left midbrain, and the left caudate nucleus (B).
5. Conclusion
Diagnosing GCA in patients presenting with IS/TIA is challenging, as hallmark features such as constitutional symptoms, GCA‐related pain, ocular‐orbital ischemia, and temporal artery inflammation may be absent in up to one‐fifth of cases or only recognized retrospectively. Compared to other patients with GCA, those with IS/TIA exhibit less systemic inflammation but more ischemic manifestations, including jaw claudication and ocular‐orbital ischemia. Clinicians should consider GCA in patients aged ≥ 50 years presenting with vertebrobasilar involvement, multifocal infarcts affecting both vertebrobasilar and carotid territories, or recurrent IS/TIA despite optimal secondary prevention. Neuroimaging findings such as lesions centered on the distal extradural segments of the vertebral and internal carotid arteries without significant intracranial extension, bilateral vertebral artery occlusion, and MCP watershed infarcts strongly suggest GCA. These clinical and radiological markers may help identify high‐risk patients who warrant prompt GCA evaluation and treatment, potentially preventing further ischemic events.
Author Contributions
Conceptualization (J.‐P.M., S.L.), methodology (A.‐M.V., M.C.‐L., J.‐P.M., S.L.), software (A.‐M.V., J.‐P.M.), data curation (A.‐M.V., M.P.‐C., J.‐P.M., S.L.), investigation (J.‐P.M., S.L.), validation (A.‐M.V., M.P.‐C., J.‐P.M., S.L.), analysis (A.‐M.V., M.P.‐C., M.C.‐L., CR, J.‐P.M., S.L.), supervision (J.‐P.M., S.L.), visualization (J.‐P.M., S.L.), project administration (J.‐P.M., S.L.), writing – original draft (A.‐M.V., M.C.‐L.), and writing – review and editing (C.R., J.‐P.M., S.L.).
Funding
The authors have nothing to report.
Ethics Statement
The authors confirm the originality of the manuscript. Ethical approval was not required for our review of published data and the case we report, in accordance with the local legislation and institutional requirements. Written informed consent was obtained from the case we report.
Conflicts of Interest
The authors declare no conflicts of interest.
Supporting information
DATA S1: ene70462‐sup‐0001‐Supinfo1.docx.
Vergara A.‐M., Perez‐Caceres M., Chayer‐Lanthier M., Ross C., Makhzoum J.‐P., and Lanthier S., “Markers of Giant Cell Arteritis in Patients Presenting With Ischemic Stroke: A Scoping Review,” European Journal of Neurology 32, no. 12 (2025): e70462, 10.1111/ene.70462.
Data Availability Statement
Data sharing not applicable to this article as no datasets were generated or analysed during the current study.
References
- 1. Crowson C. S., Matteson E. L., Myasoedova E., et al., “The Lifetime Risk of Adult‐Onset Rheumatoid Arthritis and Other Inflammatory Autoimmune Rheumatic Diseases,” Arthritis and Rheumatism 63 (2011): 633–639. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Salvarani C., Cimino L., Macchioni P., et al., “Risk Factors for Visual Loss in an Italian Population‐Based Cohort of Patients With Giant Cell Arteritis,” Arthritis and Rheumatism 53 (2005): 293–297. [DOI] [PubMed] [Google Scholar]
- 3. Chen J. J., Leavitt J. A., Fang C., Crowson C. S., Matteson E. L., and Warrington K. J., “Evaluating the Incidence of Arteritic Ischemic Optic Neuropathy and Other Causes of Vision Loss From Giant Cell Arteritis,” Ophthalmology 123 (2016): 1999–2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. Gonzalez‐Gay M. A., Vazquez‐Rodriguez T. R., Gomez‐Acebo I., et al., “Strokes at Time of Disease Diagnosis in a Series of 287 Patients With Biopsy‐Proven Giant Cell Arteritis,” Medicine 88 (2009): 227–235. [DOI] [PubMed] [Google Scholar]
- 5. Larivière D., Sacre K., Klein I., et al., “Extra‐ and Intracranial Cerebral Vasculitis in Giant Cell Arteritis: An Observational Study,” Medicine 93 (2014): e265. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Salvarani C., Della Bella C., Cimino L., et al., “Risk Factors for Severe Cranial Ischaemic Events in an Italian Population‐Based Cohort of Patients With Giant Cell Arteritis,” Rheumatology 48 (2009): 250–253. [DOI] [PubMed] [Google Scholar]
- 7. Solans‐Laqué R., Bosch‐Gil J. A., Molina‐Catenario C. A., Ortega‐Aznar A., Alvarez‐Sabin J., and Vilardell‐Tarres M., “Stroke and Multi‐Infarct Dementia as Presenting Symptoms of Giant Cell Arteritis: Report of 7 Cases and Review of the Literature,” Medicine 87 (2008): 335–344. [DOI] [PubMed] [Google Scholar]
- 8. Farina N., Tomelleri A., Campochiaro C., and Dagna L., “Giant Cell Arteritis: Update on Clinical Manifestations, Diagnosis, and Management,” European Journal of Internal Medicine 107 (2023): 17–26. [DOI] [PubMed] [Google Scholar]
- 9. De Boysson H., Liozon E., Larivière D., et al., “Giant Cell Arteritis‐Related Stroke: A Retrospective Multicenter Case‐Control Study,” Journal of Rheumatology 44 (2017): 297–303. [DOI] [PubMed] [Google Scholar]
- 10. Pariente A., Guédon A., Alamowitch S., et al., “Ischemic Stroke in Giant‐Cell Arteritis: French Retrospective Study,” Journal of Autoimmunity 99 (2019): 48–51. [DOI] [PubMed] [Google Scholar]
- 11. Parreau S., Dumonteil S., Montoro F. M., et al., “Giant Cell Arteritis‐Related Stroke in a Large Inception Cohort: A Comparative Study,” Seminars in Arthritis and Rheumatism 55 (2022): 152020. [DOI] [PubMed] [Google Scholar]
- 12. Bonnan M. and Balley G., “Stroke Pattern in Giant‐Cell Arteritis Mostly Involves Watershed Areas,” Clinical Neurology and Neurosurgery 245 (2024): 108520. [DOI] [PubMed] [Google Scholar]
- 13. Tricco A. C., Lillie E., Zarin W., et al., “PRISMA Extension for Scoping Reviews (PRISMA‐ScR): Checklist and Explanation,” Annals of Internal Medicine 169 (2018): 467–473. [DOI] [PubMed] [Google Scholar]
- 14. Ponte C., Grayson P. C., Robson J. C., et al., “2022 American College of Rheumatology/EULAR Classification Criteria for Giant Cell Arteritis,” Annals of the Rheumatic Diseases 81 (2022): 1647–1653. [DOI] [PubMed] [Google Scholar]
- 15. Chazal T., Couture P., Rosso C., et al., “Cerebrovascular Events Are Associated With Lower Survival in Giant Cell Arteritis: A Case‐Controlled Multicenter Study,” Joint Bone Spine 85 (2018): 383–385. [DOI] [PubMed] [Google Scholar]
- 16. Labropoulos N., Nandivada P., and Bekelis K., “Stroke of the Posterior Cerebral Circulation,” International Angiology 30 (2011): 105–114. [PubMed] [Google Scholar]
- 17. Nouh A., Remke J., and Ruland S., “Ischemic Posterior Circulation Stroke: A Review of Anatomy, Clinical Presentations, Diagnosis, and Current Management,” Frontiers in Neurology 5 (2014): 30. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18. García‐García J., Ayo‐Martín Ó., Argandoña‐Palacios L., and Segura T., “Vertebral Artery Halo Sign in Patients With Stroke: A Key Clue for the Prompt Diagnosis of Giant Cell Arteritis,” Stroke 42 (2011): 3287–3290. [DOI] [PubMed] [Google Scholar]
- 19. Guisado‐Alonso D., Edo M. C., Estrada Alarcón P. V., et al., “Progression of Large Vessel Disease in Patients With Giant Cell Arteritis‐Associated Ischemic Stroke: The Role of Vascular Imaging: A Case Series,” Journal of Clinical Rheumatology 27 (2021): e418–e424. [DOI] [PubMed] [Google Scholar]
- 20. Elhfnawy A. M., Elsalamawy D., Abdelraouf M., Schliesser M., Volkmann J., and Fluri F., “Red Flags for a Concomitant Giant Cell Arteritis in Patients With Vertebrobasilar Stroke: A Cross‐Sectional Study and Systematic Review,” Acta Neurologica Belgica 120 (2020): 1389–1398. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21. Rüegg S., Engelter S., Jeanneret C., et al., “Bilateral Vertebral Artery Occlusion Resulting From Giant Cell Arteritis: Report of 3 Cases and Review of the Literature,” Medicine 82 (2003): 1–12. [DOI] [PubMed] [Google Scholar]
- 22. Spasojevic G., Vujmilovic S., Vujkovic Z., et al., “Internal Carotid and Vertebral Arteries Diameters and Their Interrelationships to Sex and Left/Right Side,” Folia Morphologica 79 (2020): 219–225. [DOI] [PubMed] [Google Scholar]
- 23. Zarrinkoob L., Ambarki K., Wåhlin A., Birgander R., Eklund A., and Malm J., “Blood Flow Distribution in Cerebral Arteries,” Journal of Cerebral Blood Flow and Metabolism 35 (2015): 648–654. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24. Roquer J., Lorenzo J. L., and Pou A., “The Anterior Inferior Cerebellar Artery Infarcts: A Clinical‐Magnetic Resonance Imaging Study,” Acta Neurologica Scandinavica 97 (1998): 225–230. [DOI] [PubMed] [Google Scholar]
- 25. Wilkinson I. M. and Russell R. W., “Arteries of the Head and Neck in Giant Cell Arteritis. A Pathological Study to Show the Pattern of Arterial Involvement,” Archives of Neurology 27 (1972): 378–391. [DOI] [PubMed] [Google Scholar]
- 26. Shigeyasu M., Sasaki N., Nishino S., and Sakai N., “Giant Cell Arteritis With Simultaneous Onset of Multiple Intracranial Vascular Occlusions: A Case Report,” Surgical Neurology International 13 (2022): 21. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27. Siemonsen S., Brekenfeld C., Holst B., Kaufmann‐Buehler A. K., Fiehler J., and Bley T. A., “3T MRI Reveals Extra‐ and Intracranial Involvement in Giant Cell Arteritis,” American Journal of Neuroradiology 36 (2015): 91–97. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28. Salvarani C., Giannini C., Miller D. V., and Hunder G., “Giant Cell Arteritis: Involvement of Intracranial Arteries,” Arthritis and Rheumatism 55 (2006): 985–989. [DOI] [PubMed] [Google Scholar]
- 29. McLean C. A., Gonzales M. F., and Dowling J. P., “Systemic Giant Cell Arteritis and Cerebellar Infarction,” Stroke 24 (1993): 899–902. [DOI] [PubMed] [Google Scholar]
- 30. Belenguer‐Benavides A., Vilar‐Cambies C., and Geffner‐Sclarsky D., “Enfermedad Cerebrovascular Como Primera Manifestación de Arteritis de la Temporal: Presentación de Tres Casos y Revisión de Su Patogenesis y Tratamiento [Stroke as the First Manifestation of Temporal Arteritis: Three Case Reports and a Review of Its Pathogenesis and Treatment],” Revista de Neurologia 39 (2004): 227–232. [PubMed] [Google Scholar]
- 31. Chen Z. W., Symons S. P., Young B., and Bilbao J. M., “A 24‐Year‐Old Male With Headaches,” Brain Pathology 20 (2010): 863–866. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32. Alsolaimani R. S., Bhavsar S. V., Khalidi N. A., et al., “Severe Intracranial Involvement in Giant Cell Arteritis: 5 Cases and Literature Review,” Journal of Rheumatology 43 (2016): 648–656. [DOI] [PubMed] [Google Scholar]
- 33. Mahjoub Y., McKenzie E. D., Raouf S., and Almekhlafi M., “Progressive Vertebrobasilar Vasculopathy and Stroke Secondary to Giant Cell Arteritis,” Stroke 53 (2022): e435–e438. [DOI] [PubMed] [Google Scholar]
- 34. Topakian R., Stieglbauer K., Nussbaumer K., Dreer B., Sonnberger M., and Aichner F. T., “Reversibility of Basilar Artery Stenosis Following Timely Treatment of Temporal Arteritis,” Cerebrovascular Diseases 27 (2009): 204–206. [DOI] [PubMed] [Google Scholar]
- 35. Nagel M. A., Jones D., and Wyborny A., “Varicella Zoster Virus Vasculopathy: The Expanding Clinical Spectrum and Pathogenesis,” Journal of Neuroimmunology 308 (2017): 112–117. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36. Gilden D., White T., Khmeleva N., et al., “Prevalence and Distribution of VZV in Temporal Arteries of Patients With Giant Cell Arteritis,” Neurology 84 (2015): 1948–1955. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37. Pisapia D. J. and Lavi E., “VZV, Temporal Arteritis, and Clinical Practice: False Positive Immunohistochemical Detection due to Antibody Cross‐Reactivity,” Experimental and Molecular Pathology 100 (2016): 114–115. [DOI] [PubMed] [Google Scholar]
- 38. Zenone T. and Puget M., “Characteristics of Cerebrovascular Accidents at Time of Diagnosis in a Series of 98 Patients With Giant Cell Arteritis,” Rheumatology International 33 (2013): 3017–3023. [DOI] [PubMed] [Google Scholar]
- 39. Kumral E., Bogousslavsky J., Van Melle G., et al., “Headache at Stroke Onset: The Lausanne Stroke Registry,” Journal of Neurology, Neurosurgery, and Psychiatry 58 (1995): 490–492. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 40. Chen P. K., Hsu C. Y., and Wang S. J., “Onset Headache Predicts Good Outcome in Patients With First‐Ever Ischemic Stroke,” Stroke 44 (2013): 1852–1858. [DOI] [PubMed] [Google Scholar]
- 41. Jørgensen H. S., Jespersen H. F., Nakayama H., Raaschou H. O., and Olsen T. S., “Headache in Stroke: The Copenhagen Stroke Study,” Neurology 44 (1994): 1793–1797. [DOI] [PubMed] [Google Scholar]
- 42. Hočevar A., Ješe R., Tomšič M., and Rotar Ž., “Risk Factors for Severe Cranial Ischaemic Complications in Giant Cell Arteritis,” Rheumatology 59 (2020): 2953–2959. [DOI] [PubMed] [Google Scholar]
- 43. Flach C., Muruet W., Wolfe C. D. A., Bhalla A., and Douiri A., “Risk and Secondary Prevention of Stroke Recurrence: A Population‐Base Cohort Study,” Stroke 51 (2020): 2435–2444. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 44. Samson M., Jacquin A., Audia S., et al., “Stroke Associated With Giant Cell Arteritis: A Population‐Based Study,” Journal of Neurology, Neurosurgery, and Psychiatry 86 (2015): 216–221. [DOI] [PubMed] [Google Scholar]
- 45. Depuydt S., Sarov M., Vandendries C., et al., “Significance of Acute Multiple Infarcts in Multiple Cerebral Circulations on Initial Diffusion Weighted Imaging in Stroke Patients,” Journal of the Neurological Sciences 337 (2014): 151–155. [DOI] [PubMed] [Google Scholar]
- 46. Hart R. G., Diener H. C., Coutts S. B., et al., “Embolic Strokes of Undetermined Source: The Case for a New Clinical Construct,” Lancet Neurology 13 (2014): 429–438. [DOI] [PubMed] [Google Scholar]
- 47. Knight‐Greenfield A., Nario J. J. Q., and Gupta A., “Causes of Acute Stroke: A Patterned Approach,” Radiologic Clinics of North America 57 (2019): 1093–1108. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 48. Fernandez‐Friera L., Penalvo J. L., Fernandez‐Ortiz A., et al., “Prevalence, Vascular Distribution, and Multiterritorial Extent of Subclinical Atherosclerosis in a Middle‐Aged Cohort: The PESA (Progression of Early Subclinical Atherosclerosis) Study,” Circulation 131 (2015): 2104–2113. [DOI] [PubMed] [Google Scholar]
- 49. Oerding C., Uhlmann F., Wollmann J., et al., “Carotid Artery Stenosis and Ischemic Strokes in Patients With Giant Cell Arteritis,” TH Open 6 (2021): E40–E49. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 50. Beuker C., Wankner M. C., Thomas C., et al., “Characterization of Extracranial Giant Cell Arteritis With Intracranial Involvement and Its Rapidly Progressive Subtype,” Annals of Neurology 90 (2021): 118–129. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
DATA S1: ene70462‐sup‐0001‐Supinfo1.docx.
Data Availability Statement
Data sharing not applicable to this article as no datasets were generated or analysed during the current study.