A 65-year-old woman presented to the emergency department with right-sided hemiplegia. CTA revealed an intracerebral hemorrhage in the left caudate nucleus head and poor visualization of M1 focal portion (Fig. 1A-C). Two days later, she experienced stuporous mental deterioration and expansion of the intracerebral hematoma. Emergency DSA confirmed disconnection of the proximal left MCA with multiple nearby arterial networks. A tiny aneurysm (2.2 mm; arrow), originating from the arterial network, was detected (Fig. 1D-F). An initial attempt at an endovascular approach failed due to tortuosity and small arterial caliber. The aneurysm was subsequently confirmed microsurgically and successfully clipped to prevent rebleeding.

A 70-year-old woman presented to the emergency department with left-sided hemiplegia and a history of hypertension. Computed tomography revealed an intracerebral hemorrhage in the right basal ganglia and corona radiata, along with concomitant intraventricular hemorrhage in the right lateral ventricle (Fig. 2A). DSA showed disconnection of the right proximal MCA with a fine arterial network. Furthermore, dilation of the lenticulostriate perforating arteries suggested the presence of a pseudoaneurysm (Fig. 2B-D). Following conservative treatment, the hemorrhage resolved, and the pseudoaneurysm spontaneously disappeared without rebleeding.

A 50-year-old woman presented to the emergency department with stuporous mental changes and left-sided hemiplegia. She had been diagnosed with MMD at another institution 2 years prior and had been treated with aspirin (100 mg/day) and a lipid-lowering drug. Magnetic resonance imaging (MRI) and cerebral angiography examined on 2 years before intracerebral hemorrhage onset (age, 48 years) showed occlusion of the right proximal MCA with a fine arterial network (Fig. 3A-C). Fifteen days before symptom onset, she underwent a routine follow-up gadolinium-enhanced MRI, which showed a small enhancing nodule in the right temporoparietal region (Fig. 3D and E; arrow), likely the cause of the intracerebral hemorrhage (Fig. 3F). Subsequently, the patient underwent decompressive craniectomy and hematoma removal. During microscopic evacuation, the visible arterioles were coagulated, but no definite aneurysms were identified.

A 59-year-old man with a history of hypertension and dyslipidemia presented to an outpatient clinic with subtle gait disturbance. CTA performed on 15 years ago, when the patient was 44 years old, showed moderate stenosis on the left MCA and a normal right MCA (Fig. 4A). Current MRA showed poor visualization of right MCA cortical arteries (Fig. 4B). DSA revealed occlusion of the right MCA with a newly developed fine arterial network near the M1 segment (Fig. 4C and D). Leptomeningeal collaterals from the anterior and posterior cerebral arteries were observed supplying the MCA territory. Three-dimensional (3D) reconstruction angiography revealed a microaneurysm (Fig. 4E; arrow) and prominent dilatation of the lenticulostriate arteries (Fig. 4F).

A 42-year-old woman presented with transient left hemiplegia. MRI showed a disconnection between the proximal and distal M1 segments without evidence of acute infarction (Fig. 5A). DSA revealed occlusion of the right proximal M1 segment with a fine arterial network and a normal arterial vessel distal to the M2 segment (Fig. 5B). MR vessel wall imaging demonstrated eccentric wall thickening and enhancement of the proximal M1 segment (Fig. 5C, non-enhanced T1 weighted image; Fig. 5D, gadolinium-enhanced T1 weighted image, arrow).

The term “aplastic twig-like MCA” was first introduced in 2005 in a case series from Taiwan that described hemorrhagic strokes caused by microaneurysm rupture in patients with a T-MCA. The authors proposed that the condition results from aplasia or failed fusion of plexiform MCA arterioles during fetal development, based on angiographic and microsurgical observations [9]. In 2012, Seo et al. [13] reported 15 cases of a T-MCA, with a DSA incidence of 1.17% in a population in the Republic of Korea. The authors emphasized that all patients had unilateral lesions, normal arterial structures beyond the M2 segment of the MCA, and no transdural collaterals. Furthermore, they argued that failure of fusion in the MCA main trunk led to the formation of a T-MCA, often accompanied by anomalies in the adjacent anterior cerebral artery (ACA) [13]. In 2018, Cho et al. [1] reported 13 cases and introduced the term “Rete MCA,” suggesting a congenital origin based on microsurgical observation of the MCA stump. Most other case reports have similarly supported the view that a T-MCA is a congenital rather than an acquired anomaly.

However, recent evidence has increasingly challenged the congenital hypothesis. Ota and Komiyama [11] proposed that a T-MCA may represent a secondary collateral network that arises in response to steno-occlusive changes in the proximal MCA. Isolated anomalous changes limited to the M1 segment are unlikely to result from embryological persistence of the plexiform arteries. Furthermore, normal development of the distal MCA (M2-M4) and brain parenchyma is not correlated with probable congenital origin of T-MCA. Two case reports from Japan described de novo T-MCA formation following steno-occlusion of a previously normal M1 segment, lending support to the acquired condition hypothesis [7,10].

Based on microsurgical observations and angiographic images of T-MCA-related hemorrhagic stroke cases, some authors have proposed that the lesion is congenital. A fine arterial network clump was observed near the MCA occlusion site, along with arterial atresia of the M1 segment [1,9,17]. Most authors have argued that this fine arterial network clump is unlikely to be a secondary effect of MCA steno-occlusion and have concluded that it results from a failure of the plexiform MCA plexus to fuse during fetal development.

However, several factors suggest that a T-MCA may be an acquired secondary condition rather than a congenital one. First, if a T-MCA were due to congenital MCA plexus fusion failure, one would expect the entire MCA to be affected. Instead, only the M1 segment is involved, while the distal beyond M2 remains normal. In such cases, the development of the affected hemisphere would also likely be incomplete [11]. Second, we identified three de-novo T-MCA cases, supported by two additional case reports from Japan [7,10]. A T-MCA is rarely reported in pediatric patients; the youngest known patient being a 7-year-old boy in Canada with ischemic stroke [2]. Most cases have been reported in adults, and no pediatric patients were included in our study. Third, angiographic progression was confirmed in several patients. In one case, the arterial network proliferated over 6 years and later regressed after sufficient leptomeningeal collateral flow developed from the posterior circulation and ACA. Overall, the progression was much slower than that observed in MMD and was associated with relatively mild perfusion defects. In our study, transdural collaterals were observed in 7.8% (4/51) of patients.

The essential finding for the MMD diagnosis was “stenosis or occlusion of the terminal portion of the internal carotid artery (ICA) or the proximal portion of the anterior artery and/or the MCA” in the 2012 publication from the Research Committee on MMD of Japan [12]. However, the 2021 revision emphasized that the lesion must be centered on the terminal portion of the internal carotid artery [3]. Because a T-MCA does not involve the internal carotid artery, it does not meet the diagnostic criteria for MMD.

The collateral network pattern in a T-MCA differs from that of MMD. While MMD typically exhibits a vertical “puff of smoke” appearance of collateral arteries, a T-MCA displays a horizontal clump-like pattern [6]. In a T-MCA, collateral arteries arise from various regions, including the distal ICA and ACA, whereas in MMD, they mainly originate from the anterior choroidal and posterior cerebral arteries.

A T-MCA appears to share certain pathogenic features with adult-onset MMD in terms of anatomical region, age of onset, and angiographic features. Most T-MCA cases have been reported in East Asia, consistent with the epidemiological distribution of MMD. We hypothesize that a T-MCA progresses more slowly than MMD and is localized to the MCA region.

In our study, among the 15 patients who underwent gene analysis, 46.7% (7/15) had RNF213 gene mutations. A landmark 2011 study identified the RNF213 p.R4859K mutation in 73% (46/63) of non-familial MMD cases and in 1.4% (6/429) of the control group [8]. The high prevalence of this mutation in our patient group suggests that a T-MCA may share a pathophysiological basis with MMD. However, it remains unclear why a T-MCA selectively affects the MCA rather than the terminal portion of the internal carotid artery.

Determining whether MCA occlusion is related to chronic atherosclerosis or Moyamoya angiopathy remains challenging. In this study, the mean age of patients with a T-MCA was 54.8 years, which was higher than that of patients with MMD. There was no sex predominance in our study group, suggesting that the pathophysiology of a T-MCA differs from that of MMD. The older age distribution and equal sex ratio may indicate an association between a T-MCA and chronic atherosclerosis. In case 5, magnetic resonance vessel wall imaging with gadolinium contrast enhancement revealed eccentric wall thickening and enhancement, suggesting atherosclerotic disease rather than Moyamoya angiopathy. We hypothesize that MCA steno-occlusion and subsequent arterial network formation may result from a combination of Moyamoya angiopathy and chronic atherosclerosis.

Due to occlusion of the MCA M1 segment, the most affected vessels were the lenticulostriate arteries. A new collateral arterial network tends to form at the origin of the lenticulostriate artery, leading to various complications. Microaneurysm formation may result in subarachnoid or intracerebral hemorrhages. In case 1, a microaneurysm caused recurrent intracerebral hemorrhage in the basal ganglia. Three patients in our study had small aneurysms (<2 mm) detected on DSA and were treated conservatively. These cases showed no signs of rebleeding, and follow-up angiography demonstrated resolution of the aneurysms, suggesting they were pseudoaneurysms. Lenticulostriate artery dilatation was frequently observed on DSA, indicating underlying hemodynamic stress.

Hypoperfusion in the MCA territory is the primary cause of ischemic stroke in patients with a T-MCA. Most patients show no or mild hypoperfusion without rapid angiographic progression. Due to the slow disease progression, collateral compensation via leptomeningeal flow from the ACA and posterior circulation, as well as neoangiogenesis to the distal MCA, may help prevent ischemic stroke. Neurological symptoms and perfusion imaging should be considered for accurate evaluation and treatment planning.

The fine arterial network near the MCA occlusion site should be evaluated using 3D rotational DSA images to assess the risk of hemorrhage. Detecting this small fine arterial network is challenging on time-of-flight MRA due to small vessel caliber and low cerebral blood flow velocity at the occlusion site and in the distal MCA. As a result, the time-of-flight MRA may show an absence of flow in the MCA territory. The gold standard for diagnosis is catheter-based DSA with 3D reconstruction, which allows detailed visualization of microaneurysms and lenticulostriate artery dilatation. Collateral arteries from the ACA (particularly the A1 segment) and distal ICA are commonly observed. Cerebral aneurysms caused by hemodynamic stress in adjacent unaffected arteries have also been identified. Perfusion studies should be performed, especially in patients presenting with transient ischemic attacks or ischemic stroke, to assess the risk of further infarction.

There is currently no consensus on the optimal treatment for perfusion defects in patients with a T-MCA. Given that Moyamoya angiopathy and chronic atherosclerosis are considered key underlying pathophysiologies, treatment strategies should address both conditions. Bypass surgery or antiplatelet therapy may be considered, as in cases of MMD. Fuse et al. [4] reported that direct bypass surgery reduced hemodynamic stress on twig-like vessels. Reducing this stress may lower the risk of ischemic and hemorrhagic strokes; however, further studies are needed to validate this association.

In patients with cardiovascular risk factors, treatment of chronic atherosclerosis should also be considered. Among antiplatelet agents, phosphodiesterase inhibitors— due to their vasodilatory effects and relatively low risk of cerebral hemorrhage—may be a suitable option [5].

This study has some limitations, including its retrospective design. Moreover, only patients who underwent catheter-based cerebral angiography were included, which may have led to an underestimation of the true incidence. Genetic predisposition was not comprehensively evaluated, as only 15 patients (29.4%) were tested for the RNF213 mutation. Furthermore, diagnosing this condition relies on the subjective interpretation of angiographic images of the cerebral artery, which may compromise diagnostic accuracy.