Etiology and risk factors
Acute ischemia of AOP are uncommon, which accounted for 0.1% − 0.3% of all cerebral infarction[6, 17]. However, this is likely a conservative estimate due to the insufficient knowledge of it and limitations in their inclusion criteria[6, 18]. AOP arising from P1 segments of the PCA supply predominantly paramedian bithalami with variable contribution to the rostral midbrain or anterolateral thalami[6, 18]. In our studies, hypertension, smoking, diabetes mellitus, and hyperlipemia are risk factors for acute Percheron infarction. Small vessel disease and arteriosclerosis was the cause of acute AOP infarcts in 14 patients (61%), which is consistent with the previous reports[16, 19]. Cruz-Cosme et al[16, 19] indicated that cardioembolism was the most common cause, while only 7 cases (30%) had a potential source of cardiac embolism in our series. In addition, basilar artery dissection was seen in patient No.21 and 22. Atherosclerosis and small vessel disease are the main causes of acute AOP infarction.
Relationship imaging diagnosis and clinical features
Acute AOP ischemia has great variability with respect to symmetry, size, and territory, which is mainly due to the thalamic arteries vary between individuals with respect to the parent vessel from which each branch arises, the number and position of the arteries and their tributaries[1, 2, 16, 20, 21]. Paramedian bithalami of the 23 patients showed high signal intensity on FLAIR with restricted diffusion and hypointense in the ADC map (positive in 100%). Valentina Francioni et al. show a DWI/FLAIR mismatch typical of hyperacute paramedian bithalami ischemia, which points out the DWI and ADC map is very important for the differentiation and therapy in acute AOP infarction. Although head CT is not sensitive to acute AOP infarction, it is indispensable to exclude cerebral hemorrhage at admission. Adam MacLellan et al. identified a case describing AOP ischemic on acute CT perfusion imaging for the first time, however, thrombolysis was not performed in that symmetrical perfusion abnormalities were not recognized. Most interestingly, we found that patient No.4/8/11/14 show corresponding bithalamic ischemia changes on acute CT perfusion imaging and was given thrombolysis to avoid deterioration. DSA rarely show the presence of AOP, more often than not, the AOP are too small to be visualized by angiography. Similarly, although the AOP is rarely visualized with conventional MRA, it is very valuable to observe the stenosis of BA and PCA by MRA. Obstruction of the AOP oftentimes leads to ischemia of the midbrain (57%) and/or the anterior thalamus (19%) while we found that acute infarction of the rostral midbrain was present in 30% and anterior thalamus in 13%. The polar artery is absent in 30% − 60% of the population in that PcomA is highly variable (absent or hypoplastic). Then, paramedian arteries not only may supply the paramedian but also the anterior thalamic territories, especially when the polar artery is absent (Fig. 2B)[1, 3, 12, 25, 26]. Therefore, an infarction of the paramedian bithalamus and the anterior thalamus may be explained by occlusion of a single AOP, rather than synchronous occlusions of an AOP and the polar artery. In addition, patient No.7 showed bilateral paramedian thalamic infarction with only left red nucleus. Similar to previous studies[9, 10], we also analysis the relationship between AOP infarction region and clinical presentation. Based on previous report[6, 9], we found 4 different AOP infarction patterns: (1) bilateral paramedian thalamic infarction (BPTI, 52%), (2) bilateral paramedian thalamic with rostral midbrain infarction (BPTRMI, 30%), (3) bilateral paramedian and anterior thalamic infarction (BPATI, 13%), and (4) bilateral paramedian thalamic with red nuclei infarction (BPTRNI, 4%). No case involving bilateral paramedian and anterior thalamic infarction with midbrain involvement was found. The thalami contain reticular and intralaminar nuclei, associative nuclei, effector nuclei, sensory nuclei and limbic nuclei. Acute infarction of AOP destroy these nuclei in different combinations and result in complex syndromes depending on which nuclei are involved. The typical clinical symptoms are "altered mental status, vertical gaze palsy, and memory impairment". Other symptoms include: disorientation, hemiplegia, cerebellar ataxia, movement disorders and dysarthria[1, 6]. Disorder of consciousness in 22 cases, except patient No.15, may be due to involvement of the reticular activating system. Excitedly, recent evidences suggest that the paraventricular nuclei supplied the AOP is a key wakefulness-controlling nucleus in the thalamus. The vertical gaze palsy observed in patient No.2/10/13/18/20 with BPTRMI is due to an associated involvement of the midbrain tegmentum, which including the interstitial nucleus of Cajal and rostral interstitial nucleus medial longitudinal fasciculus (RINMLF). Meanwhile, vertical gaze palsy in patient No.1/15/19 with BPTI were also reported, which is because the thalami having a vital role in cortical input processing to the RINMLF. Memory dysfunctions were reported in patient No.3/5/9/10/11/19/23 cases (BPATI in patient No.5/11/19). The dorsomedial nucleus located in paramedian territory had supplied by the AOP, the mammillothalamic tract and anterior nucleus located in anterior territory had supplied by polar artery or AOP, which are commonly implicated in memory function[29, 30]. When the anterior thalamic territory is also involved, memory impairment is typically more severe[29, 30]. In our series, patient No.5/11/19 with BPATI still had serve memory deficit after 90 days. Oculomotor nerve palsy including ptosis, ocular movement disorders and ocular abnormal reflexes in patient No.2/6/10/13/18/20 with BPTRMI were related to acute ischemia of the oculomotor nucleus located in near midline of mesencephalic. The mesencephalothalamic or thalamopeduncular syndrome included movement disorders, hemiplegia and cerebellar ataxia occurs in patients with BPTRMI[8, 31], which is have a bearing on midbrain involvement. The superior mesencephalic or rubral artery branched separately from P1 segment of the PCA or share a common origin with AOP have supplied blood to the interpeduncular nucleus, medial part of the red nucleus, nucleus of cranial nerve III and anterior part of the periaqueductal gray matter located in dorsal midbrain[1, 7, 9, 31]. Similar to polar artery, a single AOP may result in BPTRMI, rather than synchronous occlusions of an AOP and the superior mesencephalic or rubral artery.
Treatment and prognosis
In this study, 65% of the patients who had a favorable outcome. Complete recovery from bilateral paramedian thalamic infarction has occasionally been reported. Current, objectives of a treatment regimen for acute AOP occlusion are to promote recanalization. Patient No.4/8/11/14/16/19 were treated with thrombolytic therapy without cerebral hemorrhage or edema found within 6 hour present on head CT, patient No.4 was full patient recovery with residual absence of cognitive impairment (mRs score=0), as well as patient No.8/11/14/16/19 was fully conscious with partial memory deficit (mRs score༝1). At the moment, thrombolytic therapy (time window<4.5h-6h) is the most effective treatment for acute AOP occlusion, our result is consistent with previous studies. Patients with outside 6h/contraindicated of thrombolysis were treated with antiplatelet and heparin. We found a favorable outcome (mRs score=1 or 2, except patient No.7) in patient No.1/3/5/12/15/17/21/22/23 with BPTI. Meanwhile, an unfavorable outcome (mRs score༝3 or 4) was present in patient No.2/6/9/13/18/20 with BPTRMI, which was consistent with previous studies[10, 16]. Cassourret G et al. have reported a cases with unconsciousness that have marked cognitive and motor improvement but still with partial memory deficit by intravenous heparin on day 2 after onset. Oral anticoagulants have been prescribed to 23 patients to prevent future episodes. Based on reported literature and our cases, we present evidence for a treatment algorithm for acute AOP infarction once linical characteristics is classical or has been confirmed DWI and ADC map (Fig. 3).
There are some other etiologies to consider, such as the “top of the basilar” syndrome, deep venous infarction by thrombosis, wernicke's encephalopathy and diffuse midline gliomas, which should not be confused with AOP infarction (Fig. 4). A single large embolus at the basilar artery tip could mimic acute AOP infarction pattern, but it often with additional characteristic cerebellar, brainstem and occipital lobe infarcts. Deep venous infarction by thrombosis and diffuse midline gliomas do not involve the specific blood-supply territory of the AOP but rather involve multiple arterial regions. Wernicke's encephalopathy affects not only the thalamus but also the mammillary bodies, tectal plate, and periaqueductal area. Diffuse midline gliomas in bilateral thalamus with space-occupying effect are hypointense on T1WI and hyperintense on T2WI or FLAIR as well as isointensity on DWI.