Limb-shaking transient ischemic attack progressing to cerebral infarction in moyamoya angiopathy: case report

Abstract

Background

Limb-shaking transient ischemic attack (LS-TIA) is a special type of TIA, typically attributed to atherosclerotic carotid stenosis and only rarely associated with moyamoya angiopathy. The manifestation of LS-TIA can sometimes lead to a misdiagnosis as epileptic seizures.

Case presentation

This report presented a young female patient who was admitted with a two-month history of recurrent left upper limb tremors, followed by the sudden onset of limb weakness. Clinical evaluation confirmed LS-TIA, which subsequently progressed to acute cerebral infarction. Digital subtraction angiography revealed severe stenosis of the right internal carotid artery and occlusion of the right middle cerebral artery, aligning with symptoms of suspected moyamoya disease. Antiplatelet drug treatment was ineffective, while the symptoms were relieved after surgical treatment.

Conclusion

This case highlights the need to consider LS-TIA in patients presenting with episodic limb tremors, particularly when standard etiologies are absent. Early recognition through neuroimaging and electroencephalography, along with timely intervention, is critical for preventing stroke and improving clinical outcomes.

Background

Limb-shaking transient ischemic attack (LS-TIA), a rare form of TIA, is characterized by episodic, stereotyped, and arrhythmic involuntary movements in one or more limbs lasting from seconds to minutes. It is associated with internal carotid artery stenosis and/or occlusion. Atherosclerosis and plaque formation are the most frequent etiologies of LS-TIA [1], and moyamoya angiopathy accounts for less than 5% of the etiologies [2]. Moyamoya refers to the formation of an abnormal vascular network secondary to progressive stenosis or occlusion of the intracranial internal carotid arteries and, in rare cases, the basilar and posterior cerebral arteries. Patients with identifiable underlying causes, such as atherosclerosis, radiation injury, or autoimmune diseases, are diagnosed with moyamoya syndrome. In contrast, moyamoya disease is characterized as a bilateral, idiopathic condition, while unilateral vasculopathy without a clear etiology is classified as suspected moyamoya disease. The incidence of moyamoya angiopathy peaks in 5-year-old children and adults around their 40s [3, 4]. This report presented the case of a young adult with untreated LS-TIA, which ultimately progressed to cerebral infarction. Imaging revealed suspected moyamoya disease involving the right middle cerebral artery (MCA), and significant improvement was found after superficial temporal artery (STA)–MCA anastomosis. LS-TIA is frequently misdiagnosed as epileptic seizures, leading to delayed treatment. This case was discussed using the existing literature to improve understanding of this clinical presentation.

Case presentation

A 34-year-old woman was admitted to the Neurology Department of the Affiliated Hospital of Southwestern Medical University (Luzhou, China) on 7th February, 2023, with complaints of “recurrent episodes of left upper limb tremors for 2 months, and numbness and weakness of the left upper limb for 2 days”. Two months before admission, the patient began experiencing episodic left upper limb tremor without obvious causes, which manifested as alternating palm clenching and stretching, occurring two to three times per day and lasting several minutes. She reported no fever, headache, palpitation, impaired consciousness, diplopia, dysphonia, motor or sensory disorders, or incontinence. The symptoms were initially disregarded. Two days before admission, she developed left upper limb weakness, presenting as an inability to make a fist, grasp objects, and lift the arm, accompanied by numbness in the left palm. Since the onset of the symptoms, her general condition remained stable. She reported no history of hypertension, diabetes mellitus, or hyperlipidemia. She had no previous seizures and no history of smoking or alcohol use. Her family history showed no indication of hereditary diseases.

The patient’s vital signs were normal and stable. Cardiopulmonary and abdominal physical examination indicated no abnormality. The patient was fully awake and conscious. The left nasolabial fold appeared flattened relative to the right one, and her tongue deviated to the left on protrusion. When baring the teeth, the corners of the lips skewed to the right side. The muscle strength of the left upper limb was graded as IV proximally and III distally. The National Institutes of Health Stroke Scale (NIHSS) score was 2 (1 point for facial palsy and 1 point for left arm weakness), and the Modified Rankin Scale (mRS) score was 2.

Results of laboratory tests indicated no abnormality. No definite epileptiform activities were identified using dynamic electroencephalogram (EEG) (Fig. 1). Brain CT revealed a blade-shaped hypodense area in the right frontoparietal lobe, suggestive of cerebral infarction, along with scattered foci of encephalomalacia in the right centrum semiovale and right basal ganglia. Further magnetic resonance imaging (MRI) of the brain (Fig. 2A-D) confirmed subacute cerebral infarction of the right frontoparietal and temporal lobes and the insula, multiple lacunar infarcts in the bilateral lateral paraventricular regions, and encephalomalacia in the right centrum semiovale. The infarction of the right motor cortex and the underlying corticobulbar fibers corresponded to the patient’s symptoms.

Fig. 1.

EEG displaying no definite epileptiform discharges

Fig. 2.

A-D Axial T1-weighted, T2-weighted, diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) sequences, respectively, demonstrate a hypointense signal on T1, hyperintense signals on T2 and DWI, and a corresponding low ADC value in the right frontoparietal, temporal, and insular regions, consistent with subacute cerebral infarction. E, F DSA reveals progressive stenosis of the distal C6–C7 segments (Bouthillier category) of the right internal carotid artery, with severe narrowing at C7 and near-total occlusion at the origin of the right MCA. Prominent neovascularization is observed, as well as reduced and delayed perfusion in the M2 segment and more distal branches. G DSA of the left internal carotid artery and MCA displays no significant stenosis or occlusion

Digital subtraction angiography (DSA) was carried out (Fig. 2E-G), revealing progressive and severe stenosis in the distal C6-C7 segments (Bouthillier category) of the right internal carotid artery, along with complete occlusion of the right MCA. Markedly reduced and delayed blood flow was found in the M2 segment and distal branches, accompanied by extensive neovascularization. No evidence of common causes of moyamoya syndrome was identified, and the patient declined further etiological evaluation. Consequently, a diagnosis of suspected moyamoya disease was made. No genetic testing for ring finger protein 213 (RNF213) was conducted. After being treated with antiplatelets (aspirin and clopidogrel), no symptomatic improvement was found. She was then discharged and underwent STA-MCA anastomosis surgery one month later in another hospital. At the six-month follow-up, her facial palsy and muscle weakness were relieved, and her left hand regained the ability to perform basic daily activities. No recurrent tremor episodes were reported.

Discussion and conclusions

In this study, a young female patient was reported, presenting with recurrent limb tremors followed by exacerbation and progression to limb weakness and facial palsy. No common cerebrovascular risk factors were identified in the patient, such as hypertension, hyperlipidemia, diabetes, or even hereditary factors. Dynamic EEG exhibited no evidence of epileptiform waves. Contrast-enhanced MRI of the brain revealed a subacute cerebral infarction in the right frontoparietal, temporal, and insular regions. Subsequent DSA demonstrated significant stenosis of the right ICA and complete occlusion of the right MCA. The patient’s primary manifestation, left-sided acute-onset muscle weakness, was consistent with the clinical course of a cerebrovascular event. MRI confirmed cerebral infarction and ruled out neoplastic lesions, and the lesion location was correlated with the vascular territory and neurological deficits. On the basis of these findings, the diagnosis of acute cerebral infarction in the right cerebral hemisphere was made, categorized as “other determined etiology” according to the TOAST classification. DSA revealed unilateral occlusion of the right MCA with downstream blood flow reduction and vascular network formation. In the absence of identifiable secondary causes and regarding the minimal differences in management between moyamoya disease and moyamoya syndrome, as well as the patient’s decision to decline additional evaluations, a final diagnosis of suspected moyamoya disease was made. Based on the Suzuki staging system, angiographic findings were consistent with stage III.

LSS was initially described and defined by Fisher in 1962 as a paroxysmal movement disorder associated with carotid stenosis [5]. Subsequently, Baquis et al. classified it as a special form of transient ischemic attack, and named it LS-TIA [6]. Its primary clinical features include involuntary shaking of one limb, characterized by recurrent, focal, stereotyped, and transient episodes. The upper limb is most commonly affected, and attacks are frequently triggered by postural changes, such as standing up or stretching the neck, lasting from seconds to minutes [7]. In some cases, bilateral limb involvement or even tremor involving all four limbs or the face has been reported [8, 9]. The etiology and pathogenesis of LS-TIA remain unclarified, although the “hypoperfusion theory” is supported by the majority of current research. This theory posits that due to intracranial vascular abnormalities and impaired cerebrovascular autoregulation, certain triggers may lead to transient cerebral hypoperfusion, resulting in cortical ischemia and hypoxia, followed by disinhibition, ultimately causing transient limb shaking [10–12]. In the present case, hypoperfusion was considered as the most likely mechanism. Although typical triggers, such as postural changes or hyperventilation were not identified, further assessment revealed that emotional fluctuations preceded the attacks.

Reviewing prior studies indicated that nearly 20% of patients with LS-TIA have been misdiagnosed with epilepsy and unnecessarily treated with antiepileptic drugs [2, 13]. The most frequently reported cause of LS-TIA is atherosclerotic carotid stenosis, while fewer than 10 cases associated with moyamoya angiopathy were reported [12–15]. Rarer etiologies include PHACE syndrome, a neurocutaneous disorder involving arterial, cardiac, brain, ocular, and facial anomalies [16], as well as cervical radiotherapy and carcinoma [2]. The treatment method for LS-TIA concentrates on increasing cerebral perfusion, improving circulation, and mitigating stroke risk. Pharmacotherapy consists mainly of antiplatelet agents and lipid-lowering drugs for atherosclerosis. Regarding surgical intervention, several systematic reviews and case reports suggested that revascularization targeting the culprit vessel yields definitive therapeutic benefits and may be superior to medicine. Prompt diagnosis and timely restoration of cerebral perfusion are crucial for favorable outcomes [1, 11]. In the present case, the patient had already progressed to cerebral infarction upon admission. According to the Guidelines for the Treatment of Moyamoya Disease [4], antiplatelet therapy is recommended for moyamoya patients in the acute phase of cerebral infarction, as surgical intervention in this period may elevate the risk of perioperative stroke. Therefore, revascularization is advised after 1–3 months of antiplatelet therapy. Accordingly, this patient was initially treated with dual antiplatelet therapy for approximately two months before undergoing STA-MCA anastomosis. Postoperative follow-up demonstrated clinical improvement.

Although the infarct in this case was located in the cortex, the combination of extreme occlusive vasculopathy, classic prodromal LS-TIA symptoms, and definitive surgical response strongly supports severe cerebral hypoperfusion as the primary and central pathophysiological mechanism. The cortical infarction pattern likely reflects a terminal event—in situ microthrombosis—occurring in the setting of end-stage hypoperfusion. This underscores that infarct location alone should not be used to exclude a hypoperfusion mechanism in clinical evaluation. A limitation of this study is the lack of preoperative cerebral perfusion imaging data. However, the extremely severe stenosis and hemodynamic compromise revealed by digital subtraction angiography (DSA), the clinical course consistent with limb-shaking transient ischemic attack (LS-TIA), and the definitive clinical improvement following revascularization surgery collectively provide strong indirect evidence supporting hypoperfusion as the central underlying mechanism.

LS-TIA is typically triggered by hypoperfusion in specific brain regions secondary to underlying vascular stenosis or occlusion, and carries a significant risk of progression to cerebral infarction. This case highlights the importance of considering LS-TIA as a differential diagnosis in patients presenting with recurrent episodic limb tremors. Although both conditions can present with recurrent, stereotyped limb movements, their underlying pathophysiological mechanisms are fundamentally distinct: LS-TIA results from cortical hypoperfusion due to severe large-artery stenosis, whereas epilepsy arises from abnormal neuronal discharges. Therefore, diagnosis should not rely solely on clinical symptoms, while must be based on a comprehensive evaluation framework that integrates the following items: precipitating factors (e.g., positional changes), nature of symptoms (irregular jerking in LS-TIA vs. rhythmic clonic movements in epilepsy), level of consciousness, EEG findings (presence or absence of epileptiform discharges), and vascular imaging results. In this patient, the characteristic pre-episode emotional fluctuations, preserved consciousness, negative EEG findings, and DSA-confirmed severe occlusion of the right internal carotid artery (ICA) and middle cerebral artery (MCA) collectively provide strong evidence, confirming diagnosis of LS-TIA. Recognizing these distinguishing features is essential to avoid misdiagnosis as epilepsy and to ensure timely vascular assessment and intervention, preventing progression to cerebral infarction. Additionally, in young cases without conventional cerebrovascular risk factors, rare etiologies, such as moyamoya disease or moyamoya syndrome should be considered in the differential diagnosis.

In summary, this case highlights two key clinical insights. First, diagnosing LS-TIA does not complete the diagnostic process. Previous reports have primarily focused on distinguishing LS-TIA from epilepsy; however, this case demonstrates that even after correctly identifying LS-TIA, the diagnostic workup is not finished. In young patients without traditional vascular risk factors, symptoms should not be routinely attributed to atherosclerosis by force of habit. Instead, rare etiologies such as moyamoya disease should be included in the differential diagnosis, and comprehensive vascular imaging evaluation should be pursued.

Abbreviations

LS-TIA

Limb-shaking transient ischemic attack

TIA

Transient ischemic attack

MCA

Middle cerebral artery

STA

Superficial temporal artery

NIHSS

National Institutes of Health Stroke Scale

mRS

Modified Rankin Scale

CT

Computed tomography

EEG

Electroencephalography

MRI

Magnetic resonance imaging

DSA

Digital subtraction angiography

Authors' contributions

CL: Writing - original draft; SM: data curation; TT: writing-review editing. All authors have read and approved the final manuscript.

Funding

None.

Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

Ethics approval is not applicable. Informed written consent was obtained from the patients.

Consent for publication

Written informed consent was obtained from both the patient as well as the patient’s legal guardian. A copy of the written consent is available for review by the Editor of this journal.

Competing interests

The authors declare no competing interests.