A Case of Cerebral Large-Vessel Vasculitis Concomitant Fahr Syndrome in Systemic Lupus Erythematosus

Abstract

Introduction:

Systemic lupus erythematosus (SLE) is a heterogenous, devastating autoimmune inflammatory disease with multiorgan involvement. A variety of neurological and psychiatric symptoms may be caused by nervous system involvement, termed neuropsychiatric systemic lupus erythematosus.

Case Report:

We describe a young man newly diagnosed with SLE who had a stroke as an initial symptom and was found to have cerebral large-vessel vasculitis and Fahr syndrome.

Conclusions:

The novelties of this report are the extensive cerebral calcification demonstrated on head computerized tomography in a patient with SLE, and the depiction of an underlying vasculitis on high-resolution magnetic resonance vessel wall imaging. It is our aim to describe this atypical form of neuropsychiatric systemic lupus erythematosus onset and to make known the usefulness of the new magnetic resonance imaging techniques for the diagnosis of cerebral large-vessel vasculitis.

Systemic lupus erythematosus (SLE) is a chronic, relapsing autoimmune disease characterized by loss of tolerance, production of autoantibodies, complex immune development, and multiorgan involvement.^1–3 The nervous system is often affected and causes several neurological and psychiatric symptoms such as headache, epilepsy, stroke, affective disorders, and cognitive impairment, which is defined as neuropsychiatric systemic lupus erythematosus (NPSLE).⁴ As well as indicating high disease activity, it also predicts poor outcomes. In this study, we describe an unusual case of NPSLE with novel and intriguing findings on neuroradiology.

CASE STUDY

A 23-year-old man with abrupt onset expressive aphasia and right hemiplegia was hospitalized in our emergency room in August 2020. Neurological examination revealed lethargy, gaze, right hemiplegia, and aphasia. Admission National Institute of Health Stroke Scale (NIHSS) scored 12. The patient was previously healthy and had no history of tobacco, alcohol, or illicit drug use. Laboratory results revealed leukopenia (3.2 × 10⁹/L, normal: 4 to 10 × 10⁹/L) and low level of the complement C3 (0.531 g/L, normal: 0.700 to 1.400 g/L). Erythrocyte sedimentation rate and C-reactive protein were elevated at 23 mm/h (normal: 0 to 15 mm/h) and 26 mg/L (normal≤6 mg/L), respectively. Parathyroid hormone, serum calcium, phosphate, and alkaline phosphatase were within normal ranges. High antinuclear antibody titer (1:360) with positive anti–double‐stranded deoxyribonucleic acid antibodies (210 IU/mL) and anti-Smith antibodies (130 IU/mL) were revealed. Rheumatoid factor, anti-SSA/SSB, anti-Scl, anti-cardiolipin, anti-neutrophil cytoplasmic, and anti-β2-glycoprotein I antibodies were all negative. The cerebrospinal fluid assay showed no abnormalities. The carotid ultrasound did not reveal any abnormalities. The results of the cardiology workup, including echocardiography and Holter electrocardiogram, were not particularly noteworthy. Head computed tomography (CT) demonstrated widespread calcifications in the bilateral cerebellar dentate nuclei, basal ganglia, and subcortical white matter (Fig. 1). Bilateral watershed infarcts were seen in the brain using magnetic resonance imaging (MRI) (Fig. 2). Magnetic resonance angiography shows an abrupt drop off of signal in the C2-C4 segment of the left internal carotid artery (ICA), consistent with occlusion. Severe stenosis in the C6-C7 segment of the right ICA can also be seen (Fig. 3A). High-resolution magnetic resonance vessel wall imaging (HRMR-VWI) showed uniform, concentric, and significant vessel wall enhancement of the involved arterial segment (Figs. 3B–D). SLE was diagnosed according to classification criteria developed by the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR).⁵ The patient was treated with intravenous methylprednisolone (0.5 g/d) and immunoglobulin (20 g/d) for 3 days, followed by oral prednisolone 50 mg daily and hydroxychloroquine 0.2 g daily. Following 3 months of dual antiplatelet therapy (aspirin with clopidogrel), clopidogrel was used alone. In >2 years of outpatient follow-up, the patient has remained stable. Unfortunately, he did not prefer to undergo another MRI examination due to inability to tolerate the loud noises and the long time lying still in the MRI scanner, so we failed to determine wall pattern changes in lesioned vessels from HRMR-VWI. Nevertheless, we decided to use CT angiography as an alternative to evaluating the vascular condition and treatment efficacy. However, we did not observe any significant change in CT scans and CT angiography imaging reconstruction during the follow-up period compared with the baseline imaging (Fig. 4). According to our speculation, the inflammatory reaction caused severe damage to brain tissue and blood vessels, which is irreversible and irreparable, even if the active inflammation could be resolved after immunosuppressive therapy.

FIGURE 1.

Computed tomography on the initial admissions. The axial computed tomography of the brain reveals extensive and symmetric calcifications in the dentate nuclei, basal ganglia, and subcortical white matter bilaterally.

FIGURE 2.

Diffusion-weighted imaging on the initial admissions. The axial diffusion-weighted imaging reveals water restriction at the bilateral watershed area and the left parietal lobe cortex, indicating the presence of acute infarcts.

FIGURE 3.

Magnetic resonance angiography and high-resolution magnetic resonance vessel wall imaging on the initial admissions. Magnetic resonance angiography reveals luminal narrowing of the bilateral internal carotid artery (ICA, A), severe stenosis of the C6-C7 segment of the right ICA (A, yellow arrow) and complete occlusion of the C2-C4 segment of the left ICA (A, red arrow) can be observed. High-resolution magnetic resonance vessel wall imaging shows vessel wall uniform enhancement and concentric thickening of the right ICA (B, yellow arrowheads and D, yellow circle), as well as vessel wall-thickening and lumen obliteration, blood flow loss in the left ICA (C, red arrowheads and D, red circle), demonstrating vasculitis.

FIGURE 4.

Computed tomography and computed tomography angiography imaging reconstruction at the latest clinic visit. Computed tomography reveals multiple intracranial calcifications after 2 years of follow-up and did not detect significant change compared with the baseline imaging (A). Computed tomography angiography imaging reconstruction demonstrates focal stenosis in the right distal internal carotid artery (B, yellow arrow), while the left internal carotid artery C4-C5 segment is not visualized (B, red arrow), and there is no improvement in vascular normalization was observed after chronic immunosuppressive therapy compared with initial diagnostic imaging.

DISCUSSION

Approximately 3% to 20% of all patients with SLE will suffer an ischemic stroke, which typically occurs within the first 5 years after diagnosis, but extremely infrequently as the initial symptom of the illness.⁶ Different pathologic mechanisms are involved, including hypercoagulable states caused by antiphospholipid antibodies, endocarditis-induced embolisms, atherosclerosis, and relatively rare cerebral vasculitis.⁷ In this case, the patient presented an early-onset stroke as the initial appearance, and repeated examinations excluded antiphospholipid syndrome, cardiogenic emboli, and hypercoagulable state. MRI and magnetic resonance angiography findings evidenced cerebral infarction due to bilateral ICA occlusion. Unlike the eccentric thickening typical of atherosclerosis, HRMR-VWI revealed centripetal thickening of the injured arterial wall. Thus, lupus-related vasculitis has been proposed as a potential pathologic mechanism. Only a few reports have described radiologic findings similar to those found in our patient,^8,9 as lupus-vasculitis is uncommon and usually affects arterioles and capillaries, whereas medium-large-sized vessels are rarely involved.¹⁰ Diagnosing central nervous vasculitis has proven to be challenging, with the gold standard being a brain biopsy, which is highly invasive and only has limited sensitivity. Using neuroimaging in conjunction with clinical features can often lead to early diagnosis without the need for a brain biopsy.¹¹ MRI is the most sensitive noninvasive imaging test for cerebral large-vessel vasculitis, with certain special sequences capable of revealing wall-thickening and intramural contrast material uptake in arteries.^12,13 Central nervous sysytem vasculitis typically demonstrates multifocal, segmental, smooth, concentric enhancement and thickening of the vessel walls on HRMR-VWI.^14–17 This is thought to be caused by hyperpermeability of the endothelium and/or neovascularization, which results in leakage of contrast into the arterial wall from the lumen of the main vessel or from vasa vasorum.¹⁸ Vasculitis can be distinguished from disparate vascular diseases with similar clinical manifestations or angiographical findings by certain salient features (Table 1). In our case, HRMR-VWI played a key role in making an accurate and timely diagnosis for the patient, and greater awareness should be given to this new MRI technique.

TABLE 1.

Predominant High-resolution Magnetic Resonance Imaging Characteristics of Intracranial Artery Disease

	Vasculitis	ICAS	RCVS	MMD	Dissection
VW thickening	Circumferential	Eccentric	Circumferential	Circumferential	Eccentric or combined
Enhancement	++	++	+/−	+/−	+/−
Signal characteristics	Isointense/hypointense, homogeneous	Juxtaluminal hyperintensity, heterogenous	Isointense, homogeneous	NA	Various (intramural hematoma, T1-weighted hyperintensity)
Outer wall remodeling	Negative	Positive/negative	Negative	Negative	Positive
Others	NA	Intraplaque hemorrhage	NA	Basal collaterals	Intimal flap, double lumen, and aneurysmal dilatation

− indicates no enhancement; +, mild enhancement; ++, strong enhancement; ICAS, intracranial atherosclerosis; MMD, moyamoya disease; NA, not applicable; RCVS, reversible cerebral vasoconstriction syndrome; VW, vessel wall.

Fahr syndrome also referred to as “Bilateral striopallidodentate calcinosis” (BSPDC), is a rare neurological disorder characterized by calcium accumulating in the basal ganglia, cerebral cortex, cerebellar subcortical white matter, and dentate nucleus bilaterally, symmetrically, and abnormally, which can be clearly displayed on CT scan.¹⁹ The disease can be caused by autosomal dominant inherited pathogenic genes, or secondary to endocrine disorders, metabolic disorders, infection, or poisoning,²⁰ but resulting from SLE is extremely unusual. As reported by Haider et al,²¹ a female patient with lupus nephritis developed extensive intracranial calcifications due to calcium and phosphorus dysregulation secondary to hyperparathyroidism. Our patient presented with a broad spectrum of different calcinosis locations ranging from the deep gray matter nuclei to subcortical white matter, consistent with Fahr syndrome. Exposures to toxicants and hereditary neurological diseases were ruled out by appropriate investigations for differential diagnosis. All laboratory test results did not provide evidence for endocrine causes of abnormal calcium metabolism, infection, and tumor, which may present with similar features. The underlying mechanism is not fully understood but appears to be related to microinfarction caused by immune-mediated cerebral small vessel vasculitis and secondary dystrophic calcification.²²

CONCLUSIONS

According to our knowledge, the combination of Fahr syndrome and cerebral large-vessel vasculitis with distinct findings in neuroimaging is unique in the literature. In our report, this form of NPSLE is described in detail, and HRMR-VWI is shown to be an important tool for the diagnosis. Our purpose is to raise awareness of the atypical pattern of NPSLE, as early identification would facilitate patient-individualized treatment and improve prognosis.