Occlusive lesions of the internal carotid artery (ICA) constitute the most common cause of cerebrovascular accidents. They are usually atherosclerotic in origin, although occasionally other causes such as fibromuscular dysplasia, dissection, drugs, and vasculitic process may be responsible. Bilateral ICA stenosis is a particularly serious lesion with an annual stroke rate of 7.6% per year and an annual mortality of 43% (1). We present a case of bilateral carotid artery stenosis to highlight a rare presentation of a treatable condition.
A 59-year-old man with diabetes presented for evaluation of recurrent spells of 8 months' duration. The initial episode began with the patient nodding off at the stop lights while driving. During a spell he would be minimally responsive or appear confused with no recollection of events. Occasionally he would fall to the ground with some shaking of the extremities but no incontinence. Measurements of blood glucose from samples obtained during the episodes were always normal. Blood pressure recorded at his physician's office during an episode with dizziness was 93/60 mm Hg.
The medical history was significant for hypertension, diabetes mellitus of 12 years' duration complicated by peripheral neuropathy, and dyslipidemia. The patient had been diagnosed with idiopathic dilated cardiomyopathy 5 years prior to presentation. He had smoked a pipe but had quit 20 years previously and drank an occasional glass of wine. Both his mother and a brother had type 2 diabetes.
Investigations performed prior to our evaluation included an echocardiogram with an ejection fraction of 30–35% and a normal coronary angiogram. The patient had undergone cardiac defibrillator placement for dysrhythmia, the details of which were not available. A magnetic resonance imaging study of the head was normal, and a standard angiogram showed 80–90% smooth stenosis of the bilateral distal internal carotid arteries (greater on the left than right) and basilar artery stenosis (Figure 1). The common carotid bifurcations were free of stenotic lesions.
Examination at our institution revealed a blood pressure of 136/77 mm Hg with a pulse of 71 beats per minute while lying down, and a blood pressure of 110/71 mm Hg with a pulse of 74 beats per minute while standing. Faint right femoral and bilateral carotid artery bruits were detected. Indirect ophthalmoscopy was normal. Neurologic examination was nonfocal and revealed sensory loss to temperature and pinprick in a stocking distribution. Vibration sense was decreased in the feet. The remainder of the examination was normal.
Initial laboratory investigation revealed a hemoglobin of 12.3 gm/dl, hematocrit of 35.3%, white blood cell count of 3.7 × 109/liter, and platelet count of 355 × 109/liter. Serum sodium, potassium, and creatinine (1.0 mmoles/liter) were normal. Fasting glucose was 76 mg/dl and the glycosylated hemoglobin was 6.9%. Urinalysis was normal. Antineutrophil cytoplasmic antibody (ANCA) was not detected. Chest radiograph revealed a defibrillator with lead tips in the right ventricle, and was otherwise normal. Electrocardiogram showed left axis deviation and an old left bundle branch block. Autonomic reflex screen showed evidence of severe cardiovagal and moderately severe adrenergic impairment with relatively preserved postganglionic sudomotor function, supporting the presence of autonomic failure thought to be due to diabetic autonomic neuropathy.
Device interrogation ruled out any dysrhythmias during episodes. The orthostatic hypotension and autonomic neuropathy were noted, but the lack of diabetic nephropathy and retinopathy prompted tests for other causes of syncope in addition to the known carotid stenoses. These included a negative fat aspirate for amyloid and negative test results for insulinoma and pheochromocytoma. Iron, B12, and folate studies were normal. Cardiomyopathy was believed not to be contributory. The patient was receiving continuous therapy with carvedilol and captopril, and because many of these spells occurred in the morning, it was recommended that he take the medications later in the day.
Following discussion of the risks and benefits of neurosurgical and interventional neuroradiologic treatment options, the patient elected to undergo surgery. The operative procedure performed was right superficial temporal artery (STA) to right middle cerebral artery (MCA) bypass and encephalomyosynangiosis (EMS). Intraoperatively, the STA was noted to be thick, irregular, and pulseless. A frozen section of the vessel showed disruption of elastic lamina and infiltration of the media by mononuclear and multinucleated giant cells (Figure 2), compatible with giant cell arteritis (GCA). Rheumatology consultation was obtained. Further history obtained from the family revealed that the patient had new-onset frontal headaches along with a sensation of pulsation in the ear since about the time of his first spell. The headaches often responded to acetaminophen. After 3 months, the patient had begun to report episodic double vision and visual blurriness. He had previously mentioned these symptoms to his physicians and was thought to be migrainous. There was no history of constitutional symptoms or jaw claudication.
The history and biopsy were diagnostic of temporal arteritis. Factors favoring glucocorticoid treatment included the critical ICA stenosis and the tenuous nature of the STA-MCA graft from an inflamed vessel. The patient was treated with intravenous methylprednisolone 60 mg, and an erythrocyte sedimentation rate (ESR; 50 mm/hour) and C-reactive protein level (CRP; 16.7 mg/dl, normal <1.0 mg/dl) were obtained on postoperative day 1. The postoperative course was marked by 1 episode of pulmonary edema and abnormal mental status but an otherwise uneventful recovery.
The patient was dismissed from the hospital on a dosage of 60 mg of prednisone for 3 weeks, which was relatively rapidly tapered to 40 mg for 2 weeks and then 20 mg in an effort to minimize delay in healing. One month later the patient returned to undergo left-side STA-MCA bypass and EMS. By that point, his headache and fatigue had resolved, ESR was 4 mm/hour, and CRP level was <0.3 mg/dl. A second angiogram was not performed because it was presumed that significant carotid artery stenosis would still be present, which was the case, and that the risks of the procedure could not be justified. The postoperative course was complicated by transient neurologic dysfunction without permanent sequelae.
“A skeptical view, coupled with an appreciation of well documented neurologic complications of GCA, may sharpen diagnostic and therapeutic precision when a physician is confronted by the atypical patient with GCA” (2). The presence of longstanding diabetes and other risk factors in a case such as this strongly suggests atherosclerosis as the underlying etiology of intracranial ICA involvement. However, as this case illustrates, GCA can rarely be responsible for this serious arterial lesion. STA-MCA bypass, historically used as a revascularization procedure for moyamoya disease, was the successful surgical treatment option. Addition of EMS improves the clinical condition of the patient as well as angiographic filling by 70–80%.
Carotid artery involvement in GCA is mostly extracranial (common, external, and internal carotid) but proximal intracranial arteries may also be affected (2, 3). Atherosclerosis typically affects the cervical portion of the common and internal carotid arteries, whereas petrous and cavernous segment involvement is seen with GCA. On angiography the relatively smooth, long stenotic segments of GCA are distinguished from coarse, irregular plaque of atherosclerosis (4). Vasculitis was not a consideration initially in our patient, but a review of the angiogram in light of the histopathologic diagnosis was thought to be compatible with GCA.
In the last decade, a variety of imaging modalities have been used to image vasculitis (5) including sonography, computed tomography (CT), magnetic resonance angiography (MRA), and positron emission tomography (PET). CT and MRA have the additional advantage over conventional angiography of detecting vessel wall thickness and edema. Advantages of MRA over CT include safer contrast media, no radiation, increased sensitivity, and multiple acquisition planes. In a small study comparing MRA with PET in patients with fever and aortic inflammation, PET identified more vascular regions and correlated with clinical and laboratory markers of inflammation (6).
Clinical carotid involvement with bruit and/or decreased pulse amplitude was found to be unilateral in 8% and bilateral in 11% in 166 patients with GCA (7). Transient or permanent ischemic eye or brain lesions were more common in patients with bilateral disease (often with large artery involvement) compared with patients without large artery involvement (39% versus 20%). The frequency of fixed deficits was similar between the 2 groups. Cerebral strokes may lead to death in patients with GCA (8). Involvement of both carotid and vertebral arteries with coexistent atherosclerosis has been noted at autopsy.
The rarity of cerebral lesions in followup studies of patients with GCA who have been treated with glucocorticoids indicates treatment may prevent permanent loss of function or fatal outcome. In a large population-based retrospective cohort study to assess the risk of cardiovascular disease (9), there was a trend toward stroke with an adjusted hazard ratio of 2.1 (95% confidence interval 0.9–4.6). Risk factors for ischemic complications in patients with GCA at presentation included hypertension (odds ratio [OR] 1.8) (10), transient cerebro-ophthalmic ischemic episodes (OR 4.3), and male sex (OR 2.5), whereas the presence of systemic symptoms was protective (OR 0.3). Use of low-dose aspirin was protective (OR 0.2) (11). Anticardiolipin antibodies were seen in 21% of patients with GCA (12). ANCAs have been reported in 9–14% of patients (13). These antibodies do not predispose to any neurologic manifestation and may be an epiphenomenon nonspecifically related to vascular inflammation.
Bilateral ICA stenosis is an extremely rare presentation in GCA. A review of the literature reveals only a handful of other cases (14–18). The clinical presentation, angiographic features, and pathology in patients with bilateral ICA involvement from GCA are summarized in Table 1. Atypical cases with predominantly small vessel involvement, presence of granulomatous angiitis on intracranial vessels, and lack of demonstrable angiographic or autopsy lesions are not considered in this review, and a case with vasculitic angiographic findings but no temporal artery biopsy is also not included. It is likely that many cases of GCA-related ICA involvement occur but are not suspected antemortem; the delay in diagnosis allows progression of the arteritic process despite steroid treatment.
Table 1. Clinical presentation, angiographic findings, and outcome of patients with carotid artery stenosis and GCA*
Angiogram/pathology of STA
GCA = giant cell arteritis; ESR = erythrocyte sedimentation rate (mm/hour); STA = superficial temporal artery; ICA = internal carotid artery; CCA = common carotid artery; ACR = American College of Rheumatology; PMR = polymyalgia rheumatica.
Left leg and left arm weakness
Complete occlusion of right ICA distal to origin from CCA/STA positive
GCA possible but does not fulfill ACR criteria of age >50 years
Bitemporal head pain and total left eye blindness
Narrowing of cavernous and petrous segments of both carotid arteries/STA positive
Closest case to present except previous diagnosis of GCA present
Left facial weakness, rigidity, and left-sided weakness
Bilateral ICA occlusion 1.5 cm distal to its origin; autopsy: both ICA showed changes of GCA and recanalizing thrombi
STA not examined
Expressive aphasia, right-sided numbness of face and arm, vague history of scalp tenderness
85% stenosis in distal left ICA and less advanced stenosis in right ICA siphon/STA positive
Symptoms resolved at 4 and 15 months, history of PMR
Right lateral hemianopia and left-sided faciobrachial crural hemiparesis
Autopsy: tight stenosis of both ICA; internal hypertrophy and fibrosis with infiltration of media and elastic layer of lymphocytes and giant cells
STA not examined
The presence of bilateral carotid stenosis in patients with GCA is strongly associated with future risk of neurologic deficits. It may be difficult to separate atherosclerotic lesions from vasculitic lesions related to GCA, particularly in patients with competing comorbidities associated with vasculopathies, such as diabetes mellitus. In addition, especially in this older patient population, the 2 conditions may coexist. Rigorous attention should be given to modification of traditional atherosclerotic risk factors. Use of low-dose aspirin substantially decreases the risk of vascular complications. Early recognition and treatment with careful history taking and simple laboratory tests, and increased awareness among physicians of this rare manifestation of GCA are important to prevent disease-related morbidity and mortality.
Dr. Matteson had full access to all of the data in the study and takes responsibility for the integrity of the data.
Study design. Chowdhary, Matteson.
Acquisition of data. Chowdhary, Kallmes.
Analysis and interpretation of data. Chowdhary, Kallmes, Fulgham, Meyer, Matteson.