Case report
A case of Moyamoya disease with Graves’ disease presenting clinical and radiological improvement only after treatment for hyperthyroidism
2023 年 9 巻 p. 30-34
詳細
2023 年 9 巻 p. 30-34
Graves’ disease, an autoimmune thyroid disease that results in hyperthyroidism, is rarely complicated by progressive stenosis or the occlusion of proximal intracranial arteries. The combination of these two pathologies was classically categorized as “quasi-Moyamoya disease”, but the revised diagnostic criteria for Moyamoya disease established a new disease concept of “Moyamoya disease with Graves’ disease”, for which an appropriate treatment is still unclear. In the present case, a 35-year-old woman showed transient hemiparesis and poor concentration. After serum analysis and brain imaging, she was diagnosed as having Moyamoya disease with Graves’ disease. Her symptoms and radiological findings improved dramatically after medical treatment for Graves’ disease without any other interventions. The present case represents a valuable reference for selecting treatment steps for this rare disease with a unique pathophysiology.
A/E, all extremities; CSF, cerebral spinal fluid; DSA, digital subtraction angiography; FLAIR, fluid-attenuated inversion recovery; HDS-R, Hasegawa dementia scale-revised; ICA, internal carotid artery; 123I-IMP-SPECT, 123I-N-isopropyl-p-iodoamphetamine single photon emission computed tomography, MCA, median cerebral artery; MMSE, mini-mental state examination; MRA, magnetic resonance angiography; MRI, magnetic resonance imaging; TIA, transient ischemic attack; TPO, thyroid peroxidase; TSH, thyroid stimulating hormone.
Moyamoya disease is a progressive cerebrovascular disease that is characterized by severe stenosis/occlusion of the proximal median cerebral artery (MCA) or distal end of the internal carotid artery (ICA), with the formation of collateral vessels that look like puffs of cigarette smoke (Suzuki et al. 1969). Patients with Moyamoya disease present variable symptoms such as ischemic stroke/transient ischemic attack (TIA), intracranial hemorrhages, seizures, headaches, and cognitive or psychiatric changes (Scott et al, 2009). Graves’ disease, an autoimmune thyroid disease caused by autoantibodies of the thyroid stimulating hormone receptor, is rarely complicated by Moyamoya disease. Graves’ disease with intracranial artery stenosis was classically categorized as “quasi-Moyamoya disease”, with this disease group having certain causative complications typical of Moyamoya disease. However, it was recently discovered that elevated anti-thyroid peroxidase antibody and hyperthyroidism were more frequent in adults than had previously been expected, so the diagnostic criteria of Moyamoya disease were modified, thereby establishing the disease concept of “Moyamoya disease with Graves’ disease” rather than quasi-Moyamoya disease (Kuroda et al., 2021). The standard medical treatment options for Moyamoya disease include antiplatelet agents and surgical revascularization. Although both treatments were reported to be effective for symptomatic Moyamoya disease patients without complications, the appropriate treatment for Moyamoya disease with Graves’ disease was unclear.
In this report, we present a 35-year-old woman diagnosed as having Moyamoya disease with Graves’ disease showing transient hemiparesis and poor concentration. Her symptoms and radiological findings improved dramatically after medical treatment for Graves’ disease.
A 35-year-old woman showed poor concentration, numbness in her right hand, and transient weakness in her right limb, so she visited a local hospital. A general examination revealed hyperreflexia in all extremities (A/E) without muscle weakness. Blood tests showed elevated levels of free thyroxine (fT4, 3.43 ng/dl, normal 0.75–1.45 ng/dl) and anti-thyroid peroxidase (TPO) antibody (540 IU/ml, normal < 16 IU/ml) and decreased levels of thyroid stimulating hormone (TSH, undetectable). Magnetic resonance imaging (MRI) of her brain showed no brain infarction and magnetic resonance angiography (MRA) showed bilateral MCA stenosis (data not shown). She was referred to our hospital and was admitted for a closer examination (Fig. 1).
Clinical course of the present case: The ischemic attack and cognitive symptoms with hyperthyroidism improved dramatically after the administration of potassium iodide and thiamazole and completely disappeared after induction of cilostazol.
She was 155.5 cm tall and weighed 48.9 kg. Her blood pressure was 152/84 mmHg and her heart rate was 95 beats/minute. She had no medical or family history or past use of medication. After admission, she claimed poor concentration and general fatigue all day. A neurological examination revealed a slightly drowsy state but showed a normal score in the mini-mental state examination (MMSE, 30/30) and Hasegawa dementia scale-revised (HDS-R, 29/30), normal muscle power, generally hyperreflexia in A/E without pathological reflex, and a standard sensory system without any other abnormal findings. Serum analysis showed continuously elevated fT4 (4.79 ng/dl, normal 0.75–1.45 ng/dl), free triiodothyronine (fT3, 15.20 pg/ml, normal 2.30–4.00 pg/ml), thyroglobulin (Tb) (127.82 ng/mL, normal 3.71–35.12 ng/mL), anti-TPO antibody (998.5 IU/mL, normal upper limit 3.3 IU/ mL), and anti-TSH receptor antibody (7.53 IU/l, normal upper limit 2.00 IU/L). Serum level of TSH remained undetectable. A cerebral spinal fluid (CSF) study showed normal pressure, normal cell count (1/µl, monocyte 100%), and a normal level of protein (38 mg/dl, normal 10–40 mg/dl).
A whole body CT showed no evident features of malignancy. A brain MRI showed leptomeningeal high signal intensity (“Ivy sign”) in the frontal and parietal lobe on fluid-attenuated inversion recovery (FLAIR) images (Fig. 2A, B). An MRA revealed bilateral proximal MCA stenosis (Fig. 2C, arrowheads) with the poor depiction of distal MCA. A 123I-N-isopropyl-p-iodoamphetamine single photon emission computed tomography (123I-IMP-SPECT) image showed low accumulation in the bilateral frontal lobe (Fig. 2D, arrowheads), parietal lobe, and occipital lobe.
A brain magnetic resonance imaging (MRI) showing leptomeningeal high signal intensity (“Ivy sign”) on fluid-attenuated inversion recovery (FLAIR) (A) especially in the frontal lobe (B, arrowheads). A magnetic resonance angiography (MRA) image showing bilateral proximal MCA stenosis (C, arrowheads). A 123I-N-isopropyl-p-iodoamphetamine single photon emission computed tomography (123I-IMP-SPECT) image revealed hypoperfusion in the bilateral frontal lobe and left occipital lobe (D, arrowheads). A brain MRI at 352 days after the first symptom showing improved leptomeningeal high signal intensity (E, F) without a significant improvement of MRA finding of bilateral proximal MCA stenosis (G, arrowheads). A digital subtraction angiography (DSA) image showing bilateral MCA (left > right) stenosis with an abnormal vascular network (“moyamoya vessels”) (H, I, arrowheads).
She was diagnosed with Moyamoya disease with Graves’ disease. Cerebral angiography, which may provide detailed vessel information, was abandoned because the iodine contrast media could potentially worsen her thyroid function. We planned to treat Graves’ disease first to normalize her condition, and then perform angiography or transcatheter intervention. We started by administering 20 mg of potassium iodide followed by 15 mg of thiamazole. After the start of treatment, fT3 and fT4 gradually decreased to a normal range, and her cognitive symptom (poor concentration) disappeared 2 months after the start of this treatment. In addition, the frequency of transient muscle weakness in the right upper and lower extremities decreased to about once a month (Fig. 1).
At 352 days after the first symptom appeared, she was admitted to our hospital’s neurosurgery department for reassessment. A brain MRI showed an improvement of leptomeningeal high signal intensity (Fig. 2E, F, arrowhead). The MRA finding of bilateral proximal MCA stenosis did not improve significantly (Fig. 2G, arrowheads). A digital subtraction angiography (DSA) showed bilateral MCA stenosis (left > right, Fig 2I, black arrowhead) with an abnormal vascular network (“Moyamoya vessels”) (Fig 2H, 2I, arrowheads). After adding 200 mg of cilostazol medical treatment, her motor and cognitive symptoms completely disappeared (Fig. 1).
A typical symptom of Moyamoya disease, transient hemiparalysis, was observed in the present case, but neuropsychiatric symptoms such as poor concentration or general fatigue are relatively rare (Hiruma et al., 2022). Cognitive symptoms may occur in Moyamoya disease patients regardless of the coexistence of cerebral infarctions (Karzmark et al., 2012). Long-term hypoperfusion in specific brain regions can cause related neurocognitive dysfunction leading to progressive cognitive decline without ischemic stroke (Nakamizo et al., 2018). In the present case, our therapeutic intervention at an early stage may have prevented long-term severe cortical hypoperfusion potentially leading to the progression of cognitive decline. We speculate a relationship between vascular stenosis and psychiatric symptoms since hemiparesis and cognitive symptoms started almost simultaneously. However, we cannot exclude the possibility that psychiatric symptoms were presented merely due to hyperthyroidism, as was previously reported (Fukao et al., 2020).
In patients with Graves’ disease, a detailed examination by angiography with iodine contrast cannot be performed because it may increase the risk of thyrotoxic crisis (van der Molen et al., 2004), so MRA has become the main tool to evaluate arterial stenosis and the development of collateral vessels. In the present case, although the MRA findings did not change significantly, the “Ivy sign”, which indicates dilated blood vessels on the surface of the brain, almost disappeared, suggesting improved blood flow in the middle cerebral artery (Fig. 2B, 2F). Regarding treatment for such patients, a small number of cases showed an improvement of symptoms only with a treatment for hyperthyroidism (Ishigami et al., 2014; Sasaki et al., 2006) although their clinical and radiological outcomes varied. In Moyamoya disease with Graves’ disease, vascular stenosis due to Moyamoya disease is caused by neointimal hyperplasia, disruption of the internal elastic lamina, and medial attenuation (Fox et al., 2021). In addition, increased thyroid hormones may cause progressive vascular narrowing through a rise in vascular sensitivity to the sympathetic nervous system (Liu et al., 1994).
The present case clearly demonstrates that treatment of hyperthyroidism should be considered before antithrombotic drugs or surgical therapy for Moyamoya disease with Graves’ disease. To achieve a successful and minimally invasive treatment, staged management is recommended. This includes diagnosis of Ivy sign by MRA, initial treatment for hyperthyroidism, a detailed examination by angiography with iodine contrast media after normalization of the thyroid function, and consideration of antiplatelet agents if stenosis still persists. The present case represents a valuable reference for appropriate treatment steps for this rare disease with a unique pathophysiology.
Disclosures: The authors disclose no potential conflicts of interest.
This work was partly supported by a Grant-in-Aid for Scientific Research (C) 20K09370, 20K12044, Challenging Research 21K19572, Young Research 20K19666, 21K15190, and by Grants-in-Aid from the Research Committees (Toba K, and Tsuji S) from the Japan Agency for Medical Research and Development.
