Fulminant acephalgic giant cell arteritis with basal cerebral artery occlusion: A radiological and clinico-pathological study

A 60 year old man with no past history of note presented with a 5-week history of confusion and dysphasia of sudden onset. He denied any headaches or jaw claudication, but did report vague shoulder discomfort, which in retrospect was likely to reflect polymyalgia rheumatica. Clinical examination demonstrated a non-fluent dysphasia, subcortical cognitive impairment, unsteady gait and brisk reflexes. He was in sinus rhythm and had no carotid bruits, cardiac murmurs or stigmata of infective endocarditis. He had no vascular risk factors with the exception of a past history of smoking. Laboratory studies were significant for an erythrocyte sedimentation rate (ESR) of 66 mm/hour and C-reactive protein (CRP) of 108 mg/L. Brain magnetic resonance imaging (MRI) showed extensive ischaemic lesions involving the frontal and parieto-occipital regions (Figure 1(a)). Cerebrospinal fluid analysis and extensive vasculitis screening were normal or negative. Time of flight MR angiography suggested stenosis of the carotid and vertebral arteries at the point of dural entry into the skull base (Figure 1(b)). Catheter angiography confirmed severe stenosis of the internal carotid and vertebral arteries bilaterally at the point of dural penetration (Figure 1(c–f)). Echocardiogram was normal.

Figure 1.

Magnetic resonance imaging (MRI) and angiogram findings. Axial T2W MRI scan (a) shows multiple hyper-intense deep white matter foci compatible with ischaemic lesions. Time of flight MR angiogram (b) shows dominant left vertebral artery with focal stenosis (arrow). Digital subtraction angiogram (c–f) demonstrates focal stenosis in both internal carotid and left vertebral arteries at the point of dural penetration (arrows). Follow up MRI scan 25 days later shows multiple new T2 hyper-intense foci in centrum semi-ovale regions bilaterally (g) with a ‘rosary bead’ like pattern on the left and restricted diffusion on the Diffusion Weighted Imaging (DWI) and Apparent Diffusion Coefficient (ADC) maps (h, i) confirming multiple new deep watershed infarctions. The flow void of the left internal carotid artery is lost on axial T2W suggesting occlusion (arrow, j). Time of flight MR angiogram confirms the new finding of total occlusion of left internal carotid artery (arrows, k, l).

Within 24 hours of admission, he developed jaw claudication although still had no headache. Giant cell arteritis (GCA) was suspected and he was pulsed with a 3-day course of intravenous methylprednisolone (1 g/day) followed by oral prednisolone 80 mg/day. This led to a dramatic improvement in his jaw claudication and shoulder discomfort. A temporal artery biopsy performed within 1 week of steroid administration was negative. He was readmitted 25 days into the steroid treatment with increasing confusion and dysphasia. CRP was 17.5 mg/L and ESR 8 mm/hour. Repeat MRI brain showed multiple new internal border zone infarcts in the centrum semi-ovale (Figure 1 (g–i)) and also loss of flow void of the left internal carotid artery (Figure 1 (j)). MR angiogram confirmed new total occlusion of the left internal carotid artery at the skull base (Figure 1 (k, l)). He was treated for a presumptive diagnosis of fulminant GCA with a further 3-day course of intravenous methylprednisolone in addition to pulsed intravenous cyclophosphamide. He became increasingly encephalopathic and quadriplegic. A repeat MRI scan performed 3 weeks into cyclophosphamide treatment showed extensive new areas of cerebral infarctions in both centrum semi-ovale and right parieto-occipital lobes (Figure 2 (a, b)). A non-dominant frontal lobe biopsy showed areas of micro infarction without cerebral vasculitis or lymphoma. His condition deteriorated with new infarctions of the entire right cerebral hemisphere and the left anterior cerebral artery territory (Figure 2 (c, d)). He died 5 months into the illness. Post-mortem findings were consistent with GCA (Figure 2 (e–h)).

Figure 2.

Further new infarctions and pathological findings. A 3-month follow up scan shows multiple new areas of acute infarctions in the centrum semi-ovale and right parieto-occipital regions on the axial T2W sequences (a) with restricted diffusion (b). Pre-terminal CT scan (c, d) demonstrates new extensive infarction of the whole of right hemisphere and also left anterior cerebral artery territory. Section of the right vertebral artery (hematoxylin-eosin, original magnification ×4) showing scanty inflammation, degeneration of internal elastica, intimal neovascularisation and marked luminal stenosis due to myointimal hyperplasia. Note marked adventitial fibrosis and a small thrombus in the lumen (e). Another section of the right vertebral artery (elastic Van-Gieson stain, ×4) depicting the marked degeneration and reduplication of the internal elastic lamina. The luminal thrombus is larger at this level (f). CD3 immunohistochemical stain (original magnification ×4) of the artery showing residual T lymphocytic infiltrate in the intima and around the internal elastic lamina (g). Section from the cavernous segment of the left internal carotid artery (haematoxylin-eosin, ×20) showing two giant cells, scanty inflammatory infiltrate, degeneration and focal calcification of the internal elastic lamina (h).

GCA is a systemic granulomatous vasculitis of elderly individuals affecting large and medium sized vessels. The amount of elastic tissue in the artery dictates the site of GCA involvement, with the superficial temporal, vertebral, ophthalmic and posterior ciliary arteries being frequently involved in active GCA (1). Headache is the predominant symptom in more than two-thirds of patients but 7.5% of patients with biopsy proven ‘silent’ GCA manifest no headache (2). The headache is often non-specific, variable in intensity, character and location (2). Although the patient denied headache throughout the illness, one cannot be indisputably confident that in his confusion the symptoms of headache were existent but not conspicuous.

Stroke is an uncommon manifestation occurring in approximately 2.8–4.0% of patients (2–4). The basal cerebral vessels may be involved in the disease process with a predilection for the vertebral rather than the internal carotid arteries, particularly at the time of GCA diagnosis (2–4). Cerebral ischaemia is likely to reflect involvement of the extradural vertebral and carotid arteries with high-grade stenosis or occlusion, although inflammation of intracranial/intradural arteries may rarely occur (2–4). The basal arteries become narrower as they penetrate the dura, have less elastic tissue and no vasa vasorum, which may explain the rarity of intracranial/intradural vasculitic process (2,4). Direct extension of thrombus from the site of arteritis, or embolization from arteritic thrombosed vessels may also account for cerebrovascular ischemic events (2–4).

This case demonstrates that the radiological finding of stenosis of bilateral internal carotid and vertebral arteries at the point of dural penetration should raise suspicion of GCA in elderly patients, even in the absence of headache or other classical features of GCA.

Clinical implications

GCA can manifest with repeated episodes of cerebral ischaemia but no headache.

The radiological finding of stenosis of basal cerebral arteries in a characteristic location at the point of dural penetration should raise suspicion of GCA in elderly patients, even in the absence of other classical features of GCA.

Early diagnosis is crucial for immediate initiation of aggressive steroid and immunosuppressive treatment, despite which the condition may pursue a fulminant course.