A thyroid storm causing strokes and unmasking moyamoya

Abstract

Moyamoya disease is a rare progressive cerebrovascular condition that affects the internal carotid arteries and their major branches. This leads to the formation of a networks of collateral moyamoya vessels and can cause ischemic or hemorrhagic complications. Moyamoya syndrome is a secondary condition that presents with moyamoya vessels and is associated with other underlying causes including Down syndrome, sickle cell anemia, intracranial atherosclerosis or thyroid disease. In this case report, we discuss a 29-year-old female with Grave's disease who presented with recurrent headaches, acute intermittent numbness and paresthesia. Radiologic evaluation showed multifocal intracranial infarcts and stenosis of the bilateral internal carotid arteries and decreased caliber of the distal anterior circulation. This case highlights the importance of considering MMD/MMS as a differential diagnosis in patients suffering from headaches and/or seizures, especially in the third or fourth decades of life. Prompt diagnosis and management leads to favorable outcomes in patients with moyamoya.

Introduction

Moyamoya disease (MMD) was first described in 1957 by Takeuchi and Shimizu who reported an unknown case characterized by hypoplasia of the internal carotid arteries [1]. It is a rare cerebrovascular condition characterized by progressive stenosis of the terminal segments of the bilateral internal carotid arteries and/or their proximal branches. Reduced blood flow to the brain leads to the abnormal growth of collateral vasculature, leading to ischemic and hemorrhagic complications. The etiology of MMD remains unknown, whereas moyamoya syndrome (MMS) is a moyamoya-like vasculopathy with risk factors including Down syndrome, sickle cell anemia, intracranial atherosclerosis or thyroid disease [2]. We present a moyamoya syndrome case in a 29-year-old female patient with Grave's disease who presented with recurrent headaches, acute intermittent numbness and paresthesia.

Case report

A 29-year-old female with history of migraines without aura, presented to the emergency department with headaches for 2 weeks and acute onset numbness. Four days prior to presentation, the patient felt intermittent paresthesia in her bilateral upper and lower extremities, one limb at a time for a few hours at a time. These episodes were not associated with atypical movement or weakness. Twelve hours prior to presentation, she felt persistent paresthesia on the right side and subsequently began to have right leg and arm weakness, being unable to stand unassisted. She denied any facial drooping, slurring, confusion, or loss of consciousness. The patient stated that in the past few days she felt more agitated than usual, with greater anxiety than she normally had. In addition, she stated that she had felt a lot of palpitations and a faster than usual heart rate. Additional past medical history was noncontributory. The patient did report that there was a family history of seizures and that her mother had suffered multiple strokes.

Neurologic examination revealed diffuse weakness of the right upper and lower extremities, with intact strength on the left. The patient was intact to light touch and pinprick bilaterally, though subjectively felt the right side was slightly reduced. Cranial nerves were intact, though the patient again reported slightly decreased sensation on the right side of the face. The patient was cognitively intact, and the examination of extra neurological systems was unremarkable. Of note, the patient was seen to be agitated on exam along with tachycardia. Laboratory evaluation was notable for markedly elevated T3, T4 and undetectable TSH, which is typically seen in patients with thyroid storm with Graves’ disease.

Non contrast head CT (Fig. 1) revealed multiple hypodensities with multifocal loss of gray-white matter differentiation involving the bilateral frontal and parietal lobes. CT angiogram of the head and neck (not shown) performed immediately afterwards demonstrated narrowing of the bilateral internal carotid artery terminus with decreased caliber of the distal anterior circulation, though without occlusion. MRI (Fig. 1) showed multifocal areas of restricted diffusion within the white and grey matter, some of which correlated with the CT and demonstrated enhancement, compatible with acute infarcts. Subsequent MRA (Fig. 2) delineated multifocal stenosis involving the right ICA terminus as well as proximal M1 and A1 segments. Additionally, on the left, there was stenosis of the clinoid ICA segment extending to the origins of the M1 and A1 segments. Collateral formation from hypertrophied lenticulostriate arteries bilaterally on CTA (Fig. 3) and from hypertrophied transdural collateral arteries arising from the left superficial temporal artery were noted on MRA as well (Fig. 4). Based on her laboratory work up and symptoms, the patient was diagnosed with Graves’ disease and found to be in acute thyroid storm. The patient was initially treated medically, then transferred out to a referral center, where a combined direct and indirect bypass was performed.

Fig. 1.

Noncontrast Head CT and Brain MRI with contrast. (A) Axial CT multifocal cortical hypodensities (yellow arrow). (B) Axial DWI demonstrates restricted diffusion in the grey matter compatible with multiple cortical infarcts (yellow arrows). (C) A more inferior DWI image shows additional white matter infarcts (yellow arrows). (D) Axial T1 postcontrast shows cortical enhancement at infarct (yellow arrow) indicating acute presentation.

Fig. 2.

MRA time-of-flight. (A) Right ICA MRA shows high grade stenosis of the ICA terminus (blue arrow), proximal M1 segment (white arrow), and proximal A1 segment (yellow arrow). (B) Left ICA MRA shows a more proximal and lesser degree of stenoses at the intersection of the clinoid segment and M1 and A1 origins (yellow arrow).

Fig. 3.

CTA Head. Coronal maximum intensity projection CTA demonstrating hypertrophied lenticulostriate collateral arteries, left (red arrow) greater than right (yellow arrow).

Fig. 4.

MRA time-of-flight. Coronal maximum intensity projection MRA demonstrating hypertrophied transdural collateral arteries arising from the left superficial temporal artery (red arrow).

Discussion

Moyamoya is derived from a Japanese expression for “something hazy just like a puff of cigarette smoke drifting in the air.” It was applied to angiography findings seen at the circle of Willis on patients with concomitant steno-occlusive disease in the terminal internal carotid artery. Abnormalities and stenoses of the middle cerebral artery were also described in initial studies [1].

Subsequent evaluation distinguished 2 main categories of moyamoya, and it is crucial to distinguish between moyamoya disease (MMD) and moyamoya syndrome (MMS). MMD is a rare cerebrovascular condition characterized by spontaneous, progressive, bilateral narrowing of the distal internal carotid artery (ICA) and its main branches, resulting in the formation of an abnormal network of dilated collateral vessels [2]. The incidence of MMD ranges from 0.34 to 0.94 per 100,000 in Japan and 0.086 per 100,000 in the United States. It tends to occur in 2 main age groups: children between 3 and 6 years old and adults aged 30 to 40, with a higher prevalence in women [3].

MMS, on the other hand, presents with the primary angiographic features of MMD but is associated with underlying congenital or acquired conditions, such as Down syndrome, neurofibromatosis type 1, Turner syndrome, or sickle cell anemia. Other potential contributing factors, although not clearly linked, include autoimmune diseases like vasculitis or Graves' disease. The exact incidence of MMS is less well defined due to the absence of large, multicenter studies. However, some research suggests that MMS is more common in Western countries and is more frequent in females. In children, MMS is often associated with congenital conditions like Down syndrome and NF-1, while in older adults, it is more commonly linked to intracranial atherosclerotic disease and thyroid conditions.

Graves’ disease has been found to have a strong association with moyamoya disease. A 2018 systematic review found that hyperthyroidism, of which Graves’ disease is a subset, was more frequently associated with moyamoya disease than in subjects without. A 2023 retrospective study on over 88,180 patients in Japan found that the prevalence of MMD in Graves’ disease patients was 45.36 per 100,000. The median age of MMD onset was 39 years, with a significant female predominance (male to female ratio of 1:12). MMD was most diagnosed within one year of Graves' disease onset, with 22.5% of patients diagnosed within this period. Almost half (47.5%) of the patients with MMD underwent bypass surgery. Headaches were the most frequent symptom, and ischemic strokes along with bilateral lesions were common features [4].

Graves' disease, which can be compounded by acute thyrotoxicosis, increases sympathetic nervous system activity which contributes to vasculopathy. The carotid bifurcation and skull base vasculature, which are key areas affected by moyamoya disease, are innervated by sympathetic nerves from the superior cervical ganglion. A 1990 study found that cerebral blood flow increased by 18.8% following the excision of the superior cervical ganglion in moyamoya patients, suggesting that localized sympathetic nerve stimulation may contribute to the pathological changes seen in the carotid arteries. A subsequent study confirmed that the stiffness of the ICA was increased in patients with thyrotoxicosis. Therefore, Graves' disease may contribute to the pathogenesis of moyamoya disease through its hemodynamic effects, with acute thyrotoxicosis causing vasoactive changes leading to ischemia [5].

Computed tomography angiography (CTA), magnetic resonance angiography (MRA), and digital subtraction angiography (DSA) are effective methods for identifying, localizing, and quantifying intracranial stenosis, as well as for evaluating collateral circulation. Both CT and conventional angiography can reveal stenosis or occlusion in the arteries around the terminal segment of the intracranial internal carotid artery, in addition to showing abnormal vascular networks near the occlusive or stenotic areas during the arterial phase [6].

MRI and MRA can diagnose moyamoya disease or syndrome, and may obviate the need for invasive angiography which is considered the gold standard. The 2009 diagnostic criteria state that cerebral angiography is essential for diagnosis and must reveal at least the following: stenosis or occlusion of the terminal portion of the internal carotid artery or the proximal segments of the anterior and/or middle cerebral arteries, abnormal vascular networks near the occlusive or stenotic lesions during the arterial phase, and bilateral occurrence of these findings. However, cerebral angiography may be omitted if magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) meet specific criteria. These include MRA showing stenosis or occlusion of the intracranial internal carotid artery or the proximal segments of the anterior and/or middle cerebral arteries, and the presence of abnormal vascular networks in the basal ganglia on MRA. Additionally, if MRI reveals 2 or more visible flow voids in the basal ganglia, even unilaterally, they can be considered abnormal vascular networks. Initially these criteria needed to be applied bilaterally, although more recent reviews have stated that findings may be unilateral [7].

The Suzuki imaging staging criteria describe the progression of angiopathy in moyamoya. In Stage 1, there is a narrowing of the internal carotid artery (ICA) bifurcation. By Stage 2, the anterior cerebral artery (ACA), middle cerebral artery (MCA), and posterior cerebral artery (PCA) dilate. Stage 3 is characterized by the presence of maximal basal collaterals, with the ACA and MCA becoming smaller. In Stage 4, there is a reduction in the number of collateral vessels, and the PCA becomes smaller as well. Stage 5 sees a further decrease in collaterals, with the ACA, MCA, and PCA becoming absent. Finally, Stage 6 features extensive collaterals from the external carotid artery (ECA) to the pial vessels [7].

The progressive narrowing and blockage of intracranial blood vessels lead to a decrease in cerebral perfusion pressure. Evaluating hypoperfusion is essential as a marker for stroke risk and quantitative, objective marker for determining the effectiveness of revascularization treatments. First-pass contrast-enhanced imaging techniques, such as CT perfusion (CTP) can be utilized to measure cerebral blood flow (CBF) and cerebrovascular reserve (CVR). By directly correlating the contrast agent's concentration and tissue radiographic attenuation, temporary elevations in attenuation are obtained that reflects regional concentration. Specialized software then generates perfusion maps for parameters such as CBF, cerebral blood volume (CBV), mean transit time (MTT), and time to peak. While baseline CTP parameters cannot predict CVR in moyamoya disease (MMD), the percentage change in CBF following intravenous acetazolamide administration is a critical factor linked to stroke risk. Additionally, MTT has been found to significantly correlate with the disease's angiographic stage [3].

In recent years, high-resolution (HR) vessel wall imaging has become a valuable tool in the differentiation of intracranial vasculopathies, focusing on factors such as the pattern of stenosis (whether concentric or eccentric) and vessel wall enhancement. A 2020 study involving 21 patients indicated that vessel wall imaging may be more precise than MRA in distinguishing between moyamoya disease and atherosclerotic moyamoya syndrome [8].

Conservative treatment with antiplatelet drugs has been used to prevent strokes in moyamoya disease (MMD), but its effectiveness is uncertain. A large study found that antiplatelet therapy did not reduce the risk of recurrent cerebral infarctions, likely due to MMD's hemodynamic nature rather than embolic causes. While ischemic symptoms and impaired cerebral blood flow are the main reasons to start treatment, asymptomatic patients still have a 13.3% annual stroke risk. There is currently a lack of randomized trials to support antiplatelet therapy for asymptomatic MMD. A 10-year Japanese study found no significant benefit of antiplatelet use in reducing infarction rates, highlighting that revascularization surgery remains the most effective treatment for both hemorrhagic and ischemic cases of MMD. Surgical revascularization improves blood flow and stabilizes cerebrovascular function, reducing stroke risk. Though there is no consensus on the best surgical approach, direct bypass has shown better clinical outcomes compared to indirect or combined methods [6].

Learning points

• 1.Moyamoya disease is a rare progressive cerebrovascular condition that affects the internal carotid arteries and its major branches, leading to the development of a network of abnormal collaterals.
• 2.MMD has a bimodal presentation. It commonly affects children between 3 and 6 years old and adults aged 30 to 40, with a higher prevalence in women.
• 3.MMD as a differential diagnosis in patients suffering from headaches and/or seizures in the third or fourth decades of life, especially in females.
• 4.Computed tomography angiography (CTA), magnetic resonance angiography (MRA), and digital subtraction angiography (DSA) are effective methods for identifying, localizing, and quantifying intracranial stenosis, as well as for evaluating collateral circulation.
• 5.Treatment strategies may include medical management focused on stroke prevention. Surgical interventions such as direct, indirect or combined revascularization to improve blood flow to affected areas.

Disclaimer

The views expressed in this article are those of the authors and do not reflect the official policy of the Department of the Army, the Department of Defense, or the U.S. Government.

Patient consent

The authors have obtained patient consent per RCR guidelines. They have retained the original consent form in their permanent files.