Progressive stenosis and radiological findings of vasculitis over the entire internal carotid artery in moyamoya vasculopathy associated with graves’ disease: a case report and review of the literature

Graves’ disease (GD) is rarely complicated by moyamoya vasculopathy (MMV), resulting in ischemic stroke during thyrotoxicity [1, 2]. Management of GD is considered important to prevent recurrence [3], but MMV may progress despite the control of GD [4]. A case was recently reported in which the wall of the distal ICA was enhanced on contrast-enhanced (CE) T1-weighted imaging (T1WI), suggesting vasculitis [5]. However, no reports have described the details of the processes of progression and the lesions of the proximal ICA in MMV associated with GD. Moreover, results have not been described in these patients after treatment for vasculitis of medium-to-large vessels and several issues remain uncertain, such as treatments to prevent recurrence and progression, and characteristic radiological findings.

A 37-year-old woman presented with gradually progressing weakness of the right arm. She had a medical history of asthma only in her childhood and no notable family history. On physical examination, she showed mild paralysis of the right arm. Although she felt palpitation and sweating at times, exophthalmic and enlarged thyroid lobes were not observed. Diffusion-weighted imaging (DWI) showed cortical and subcortical infarcts in the left MCA territory (Additional file 1: Figure S1), but magnetic resonance angiography (MRA) showed almost-normal cerebral arteries or very mild stenosis of the left ICA (Figs. 1a, 2a). The vessel wall seemed thicker in the left ICA than in the right on three-dimensional (3D)-T1WI, but the difference was not clear (Additional file 2: Figure S2A). Hyperthyroidism [levels of free T3, free T4, and thyroid stimulating hormone (TSH); 10.58 pg/mL, 2.70 ng/dL, and 0.01 μU/mL, respectively], and autoantibodies related to GD [anti-thyroid peroxidase antibody (anti-TPO Ab, 148.0 IU/mL), and TSH receptor antibody (TRAb, 8.3 IU/mL)] were identified (Fig. 3). Other laboratory investigations showed unremarkable results except for leukopenia, anti-SS-A antibody (89.5 IU/mL; normal range, < 7.0 IU/mL), anti-SS-B antibody (12.4 IU/mL; normal range, < 7.0 IU/mL) and thrombin-antithrombin complex (TAT, 2.5 ng/mL; normal range, < 0.3 ng/mL). C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were negative. She was diagnosed with GD, but not with Sjogren’s syndrome, based on the normal results of Schirmer’s test and a salivary flow-rate test. Rather than methimazole, she was treated with potassium iodide (150 mg/day) for GD due to leukopenia. MRA excludes over 50% stenosis of intracranial and extracranial cerebral arteries and we could not find any major risks of cardioembolic source of embolism, through electrocardiography, echocardiography, and cardiac rhythm monitoring for over 24 h, so heparin, then warfarin (4 mg/day) were administrated as treatments for stroke as unknown etiology. Mild weakness remained at discharge.

Five months later, she presented with intermittent transient weakness of the right arm and leg. DWI did not show new infarction. Stenosis of the left ICA progressed on MRA (Figs. 1b, 2b). Thyrotoxicity was exacerbated (Fig. 3). Although argatroban was administered, attacks recurred 5 times. We started intravenous methylprednisolone (IVMP; 1000 mg/day on days 2–6), clopidogrel (300 mg on day 1, and 75 mg/day from day 2), and aspirin (300 mg on day 1, and 100 mg/day from day 2). The attacks subsequently stopped. Catheter angiography showed stenosis of the left ICA from the proximal to distal portion and CBN (Fig. 4a, b). High intensity lesion on T1 W1 in the distal portion of the left ICA was observed (Additional file 2: Fig. S2B). MMV associated with GD was diagnosed. She refused any surgery. Methimazole (15 mg/day) was started, but mild thyrotoxicity continued (Fig. 3).

We subsequently identified gradual progression in the left ICA and middle cerebral artery (MCA) on MRA (Fig. 1b-d) and 3D computed tomographic angiography. Finally, we found smooth, circumferential, concentric wall thickening with diffuse gadolinium enhancement of the left ICA from the proximal to distal portion on 3D-T1WI (Fig. 5a, b). We considered the possibility of vasculitis of medium-to-large vessels and administered prednisolone (PSL; 1 mg/kg/day) and methotrexate (MTX; 4 mg/week). Subsequently, thyroid function normalized (Fig. 3).

Six months later, PSL was reduced to 0.1 mg/kg/day, and MTX increased to 14 mg/week. Signal intensity in the left ICA and MCA increased on MRA. Catheter angiography showed development of net-like vessels, and incomplete occlusion of the ICA (Fig. 4c). By 18 months after recurrence, further improved flow in the left ICA and MCA on MRA was observed (Fig. 1e), but the vessel wall of the left ICA from the proximal to the distal portion still remained enhanced on CE 3D-T1WI in the same way as the previous one. Two years after recurrence, catheter angiography also showed improved blood flow in the left ACA, MCA and ICA, as well as mild improvement of stenosis of the terminal portion of the left ICA (Fig. 4d). We evaluated the polymorphism in c.14576 G > A (rs112735431) in the RNF-213 gene, a susceptibility gene for Moyamoya disease, using genomic DNA samples from the patient. Genetic analysis of RNF-213 showed wild type.

This report suggests the possibility of vasculitis of medium-to-large vessels in MMV associated with GD. This is the first case where cerebral infarction occurred during thyrotoxicity without obvious stenosis of ICAs. We treated the patient as having vasculitis of medium-to-large vessels with IVMP in the acute phase and with PSL and MTX in the chronic phase. Subsequently, improved flow in the cerebrovascular arteries on MRA was observed in the euthyroid state. Treatment with ATM alone seems to be risky in terms of recurrence. Adequate management of GD and possible vasculitis may be important for preventing recurrence and progression.