Intracranial Giant Cell Arteritis Progressing despite Treatment with High Doses of Corticosteroids: Case Report

Abstract

Introduction

We describe a man with severe unilateral visual loss from giant cell arteritis who had normal inflammatory markers and exhibited progression of intracranial vasculitis while on high doses of corticosteroids.

Case

A 64-year-old man presented with unilateral visual loss. He had systemic symptoms of giant cell arteritis (GCA); however, both inflammatory markers were normal. He was diagnosed with arteritic anterior ischemic optic neuropathy after temporal artery biopsy revealed classic findings of GCA and treated with high-dose corticosteroids. Despite appropriate treatment, serial imaging revealed progressive narrowing of intracranial arteries, predominantly involving anterior circulation of the brain.

Conclusion

This case highlights that GCA can rarely present with normal inflammatory markers, involve intracranial vasculature, and progress despite treatment with high doses of corticosteroids emphasizing the importance of advanced imaging and potential need for adjunctive immunosuppressive therapy in patients with refractory disease.

Introduction

We describe a 64-year-old man with biopsy-proven giant cell arteritis (GCA) who initially presented with jaw claudications, headache, and transient visual disturbances, progressing to complete vision loss in one eye. Despite treatment with high-dose corticosteroids, serial imaging revealed progressive narrowing of intracranial arteries, predominantly involving anterior circulation of the brain. This case highlights that GCA can rarely involve intracranial vasculature and vasculitis can progress despite treatment with high doses of corticosteroids emphasizing the importance of advanced imaging and potential need for adjunctive immunosuppressive therapy in patients with refractory disease.

Case Presentation

A 64-year-old man with a 2-year history of polymyalgia rheumatica (PMR) presented with new-onset headache, jaw claudications, and transient episodes of vision loss in the left eye (LE) that rapidly progressed to complete vision loss. At PMR diagnosis (2 years earlier), erythrocyte sedimentation rate (ESR) was 48 mm/h and C-reactive protein (CRP) 22 mg/L; he improved on prednisone 20 mg/d and remained on 5 mg/d at current presentation.

Vision was 20/20 in the right eye (RE) and no light perception in the LE along with pallid swelling of the left optic nerve. Inflammatory markers were both normal (ESR 2 mm/h and CRP 0.6 mg/L). CT angiogram (CTA) of the brain revealed no significant vascular abnormalities. Temporal artery biopsy was performed. A verbatim excerpt of the pathology report follows: “Sections of muscular artery show lympho-histiocytic inflammation, giant cells, and medial fibrinoid necrosis. Foci of elastic lamina disruption shown by elastic histochemical stain.” These findings confirmed GCA. Treatment with intravenous methylprednisolone commenced on the day of presentation (1 g daily for 5 days), transitioning to oral prednisone 60 mg daily. At discharge, systemic symptoms improved but there was no improvement of vision in LE.

Two weeks later, he re-presented to an emergency department with transient visual disturbance in RE that he described as seeing an arch of light that lasted seconds and did not recur. A repeat brain CTA revealed new irregular arterial narrowing of the intracranial segments of the internal carotid arteries and probably also the left ophthalmic artery (Fig. 1). The remainder of the intracranial vasculature including the middle cerebral arteries was normal. Despite persistently normal ESR and CRP levels, these findings raised concerns about poor disease control with current treatment thus a second course of pulse-doses of intravenous methylprednisolone (1 g daily for 3 days) was initiated, followed by high-dose oral prednisone (1 mg/kg). CT angiography of the chest abdomen and pelvis did not show evidence of extracranial large-vessel involvement.

Fig. 1.

Axial CTA (1 mm slice thickness) demonstrating new irregular arterial narrowing of the intracranial segments of the internal carotid arteries (a) and possibly of the left ophthalmic artery (b) on the repeat examination 2 weeks after the initial presentation. ICA, intracranial carotid artery; Opth, ophthalmic artery.

Repeat CTA of the brain 3 weeks later showed persistent irregular narrowing of the intracranial segments of the internal carotid arteries and progression of intracranial vasculitis with new narrowing of the middle cerebral arteries (M1 segments) and probable progressive involvement of the ophthalmic arteries (Fig. 2). CT angiography of the chest abdomen and pelvis remained normal. Given the refractory nature of the disease and intracranial involvement, the treatment escalated to the third course of pulse dose of corticosteroids (IV methylprednisolone 1 g daily for 3 days) and initiation of cyclophosphamide (1 g IV), with the plan to continue monthly infusions.

Fig. 2.

Coronal MIP, 3D reconstructions, and axial CTA demonstrating new irregular narrowing of the bilateral middle cerebral arteries (M1 segments) (a, b) and probable progressive involvement of the ophthalmic arteries (c). M1, 1st segment of the middle cerebral artery; Opth, ophthalmic artery.

Discussion

GCA with intracranial involvement is an exceedingly rare and complex manifestation of this systemic medium to large-vessel vasculitis. While typically GCA affects large extracranial arteries, intracranial extension challenges the traditional understanding of the disease, particularly due to the lower elastic fiber content of intracranial arteries, which historically was thought to be protective as GCA that has a predilection for affecting internal elastic lamina of the vessel wall [1, 2].

When the patient re-presented with the very short-lived visual disturbance involving initially affected eye, repeat vascular imaging demonstrated marked new abnormalities. Another unusual feature was the persistently normal inflammatory markers (seen in up to a third of GCA cases with intracranial involvement) despite new intracranial involvement by the vasculitis, highlighting the limitation of relying solely on inflammatory markers when making a decision about disease recurrence [2, 3]. In addition, the patient was on low-dose maintenance glucocorticoids for PMR, which can suppress acute-phase reactants [4]; therefore, normal ESR/CRP do not exclude active disease in PMR/GCA. Repeat imaging revealed progressive luminal irregularities of several intracranial arteries attributed to vasculitic involvement. This is consistent with the reports that intracranial GCA may present with imaging patterns of smooth stenosis or arterial narrowing, which could be misinterpreted as atherosclerotic changes in the absence of systemic inflammation [1, 2].

Our patient, though asymptomatic from the systemic perspective, demonstrated radiological progression. Given the aggressive presentation of his vasculitis, a total-body CTA was performed to assess for extracranial involvement and malignancy. In this case, brain CTA proved valuable by identifying progressive arterial stenosis, a hallmark of intracranial GCA, and revealing vascular changes initially overlooked.

Previous literature highlights CTA’s effectiveness in evaluating vessel lumen and detecting stenosis even in complex cases of intracranial vasculitis [5, 6]. Compared to MRI with vessel wall imaging, CTA offers superior spatial resolution and three-dimensional visualization of both intracranial and extracranial vessels. However, it is less effective at detecting early inflammatory changes or vessel wall thickening, where vessel wall MRI excels. Together, these modalities provide complementary diagnostic insights in challenging GCA cases [5, 6].

Although FDG-PET-CT detects mural inflammation and has high pooled accuracy in GCA [7], we prioritized urgent CTA because it was immediately available and provided rapid luminal/anatomic assessment for acute decisions. FDG vascular wall uptake drops markedly after 3 days of glucocorticoids, which the patient had already received, reducing the expected yield of PET outside this window [7]. Furthermore, PET-CT is particularly informative in extracranial large vessel whereas smaller head-and-neck and intracranial arteries are more challenging [7]. We therefore obtained an urgent CTA (available within hours) and deferred PET, which required scheduling and would not have changed immediate management.

Intracranial GCA carries a poor prognosis when untreated, with high rates of morbidity and mortality due to strokes and other cerebrovascular events [1, 3] and given its rarity the evidence for treatment is less robust. A PubMed search on May 7, 2024, for “intracranial giant cell arteritis” yielded 17 articles, summarized in Table 1 [1, 8–20]. Two studies described over 25 patients, while the others were case reports or small series. Intracranial involvement predominantly affects women (70%), with 70% of cases involving anterior circulation and 30% posterior circulation of the brain. Of 64 cases, 31 were treated with steroids and immunosuppressive agents (cyclophosphamide, methotrexate, azathioprine), and 18 resulted in death despite treatment. Using a combination of steroids and immunosuppressive agents improved outcomes, reducing the mortality rate to 40% compared to 58% with steroids alone [1].

Table 1.

Published literature on intracranial giant cell arteritis, summarizing patient demographics, intracranial vascular involvement, treatments (steroids and immunosuppressive agents), and clinical outcomes

Article and year	Patient presentation	Time from initial diagnosis	Treatment	Outcome
Arias et al. [8] (2022)	Female: GCA symptoms, dysarthria, right arm weakness, tonic-clonic seizures	4 days	Intravenous methytprednisotone (1 g/day for 3 days), oral prednisone (60 mg/day), followed by gradual tapering	Improved
Mineji et al. [9] (2023)	Female: GCA symptoms dysathria, ataxia, right upper and lower limb weakness, bilateral pons and cerebellar infraction	3 months	Oral glucocorticoids (60 mg/day), dual antiplatelet therapy	Partial improvement
Sanchez-Alvarez et al. [10] (2020)	9 patients, 78% male, 67% headache, 44% temporal artery tenderness, 33% vision loss, 89% ischemic cerebrovascular events	0.1–5.1 months	All patients received glucocorticoids, 67% cyclophosphamide, 22% tocilizumab	5 patients died
Takatsuki et al. [11] (2023)
Case 1	Female, headache, visual disturbances, lower extremity stiffness, hemiparesis, motor aphasia, acute cerebral infarction	13 days	Intravenous methytprednisolone, followed by oral prednisolone (60 mg), methotrexate (MTX), dual antiplatelet therapy	Partial improvement
Case 2	Female, headache, visual disturbances, lower extremity stiffness, hemiparesis, motor aphasia, acute cerebral infarction	2 weeks	Intravenous methytprednisolone, oral prednisolone, dual antiplatelet therapy,single balloon angioplasty procedure	Partial recovery
Parra et al. [12] (2014)	Male, GCA with extensive intracranial involvement and multiple dissections	1 month	Prednisolone 80 mg/day orally, methotrexate	Partial recovery
Tang et al. [13] (2012)	Female, GCA with non-occlusive thrombus in the left petrous ICA, scalp tenderness, jaw claudication, and visual loss	5 days	High-dose methylprednisolone IV. followed by prednisone, aspirin, and clopidogrel	partial recovery
Salvarani et al. [14] (2006)
Case 1	Female, GCA symptoms, visual disturbances, cognitive decline	12 months	Prednisone 60 mg/day, aspirin	Complete recovery
Case 2	Female, GCA symptoms, visual disturbances, cognitive decline, aphasia	3 months	Case 2: prednisone 60 mg/day, cyclophosphamide 100 mg/day	Died
Kargiotis et al. [15] (2017)	Female, acute ischemic stroke, diffuse intracranial stenosis, GCA symptoms	3 months	Prednisone 60 mg/day, aspirin	Improved
Guerrero et al. [16] (2015)	Female, recurrent transient ischemic attacks (TIAs), bilateral intracranial internal carotid artery stenosis	3 months	High-dose corticosteroids, methotrexate, aspirin, and endovascular therapy with angioplasty and stenting of the left ICA.	Improved
Neutel et al. [17] (2014)	Male, jaw claudication, elevated ESR, ischemic infarcts in the middle cerebral and posterior inferior cerebellar arteries	3 months	High-dose corticosteroids, clopidogrel, endovascular angioplasty in left ICA, methotrexate	Improved
Beuker et al. [2] (2021)	31 patients, 67.7% women, 50% headache, 63.3% vision loss, 33.3% motor deficits, 33.3% speech difficulties, 30% cerebellar symptoms	2–3 weeks (median time)	35% GC alone, 19% GC and CYC,7% GC and MTX, 13% GC and Tocilizumab, 9.7% GC, CYC, and TociIizumab, 13% GC, CYC, and MTX	36% mortality, 26% poor outcome
Prasad et al. [18] (2024)	Female, posterior communicating artery aneurysm and extracranial internal carotid artery aneurysm, jaw claudication	10 days	High-dose corticosteroids (1 mg/kg), followed by prednisone (55 mg/day)	Improved
Donaldson et al. [19] (2020)	10 cases 3 male 7 female, scalp tenderness, hemianopia, jaw claudication	1–8 days (median 3.5 days)	Corticosteroids-100%, azatioporine-10% metrotoxate-20%	3 worsen 3 improved 4 partial improved
Siemonsen et al. [3] (2015)	28 patients, 75% women, 50% headache, 35.7% visual impairment, 21.4% dizziness, 21.4% gait abnormalities	1–8 days (median 3.5 days)	Corticosteroids, 5 patients with IV steroids, some requiring additional immunosuppressive therapy (was not mentioned how many)	50% with intradural ICA involvement
Alsolaimani et al. [1] (2016)
Case 1	Male, headaches, unilateral vision loss, disorientation, right-side weakness, aphasia, cognitive changes	N/A	Prednisone 80 mg, ASA, IV cyclophosphamide, IV methylprednisolone, angioplasty	Improved
Case 2	Male, scalp tenderness, jaw claudication, vertigo, blurry vision, diplopia, dysarthria, right-side weakness, facial droop	2 weeks	IV methylprednisolone, prednisone 70 mg, IV cyclophosphamide, MTX, ASA	Partial improvement
Case 3	Female, confusion, aphasia, dysarthria, right facial droop, right-side weakness, sensory impairment	1 week	ASA, IV methylprednisolone, prednisone 70 mg, IV cyclophosphamide, MTX, left cavernous ICA angioplasty, clopidogrel	Partial improvement
Case 4	Male, bilateral occipital headaches, left facial droop, numbness, dysarthria, upper limb sensory disturbance	1 month	Prednisone 80 mg, ASA, IV methylprednisolone, continued prednisone tapering	Improved
Case 5	Female, word-finding difficulty, dysarthria, right hemiparesis, acute ischemic infarct in the left frontal lobe	3 weeks	Prednisone 50 mg, ASA, IV methylprednisolone, MTX	Improved
Shigeyasu et al. [20] (2022)	Male, multiple intracranial vascular occlusions, gait disturbance, headache, ataxia, lCA and VA stenosis and occlusion	1 month	Methytprednisolone IV, prednisolone 50 mg, antiplatelet therapy, angioplasty, and endovascular management	Died

In summary, this case highlights a rare but severe manifestation of intracranial involvement in GCA. Inflammatory markers may not reflect disease activity in cases of intracranial involvement, necessitating reliance on advanced imaging modalities for diagnosis. While high-dose steroids remain the cornerstone of therapy, this case demonstrates the necessity of escalating treatment to steroid-sparing immunosuppressive agents, such as cyclophosphamide, to mitigate the risk of catastrophic complications.

Statement of Ethics

This retrospective review of patient data did not require ethical approval in accordance with local/national guidelines (https://research.sunnybrook.ca/research/human-research-protections-program/research-ethics/faqs/). Written informed consent was obtained from the patient for publication of the details of their medical case and any accompanying images. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000550515).

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

This study was not supported by any sponsor or funder.

Author Contributions

Edward Margolin: study idea, data collection, manuscript writing, and final approval. Niv Levi: data collection, manuscript writing, and final approval. Alexandre Boutet: study idea, data collection, manuscript writing, and final approval.

Funding Statement

This study was not supported by any sponsor or funder.

Data Availability Statement

The data that support the findings of this study are not publicly available due to patient privacy but are available from Edward Margolin upon reasonable request.