Acute percheron infarction: a precision learning

Clinical workup included assessment of cardiovascular risk factors, diabetes mellitus history and evaluation of coagulation function. Evaluate the clinical risk factors of each patient, including cardiac embolism, large artery atherosclerosis or small artery occlusion.

Table 1 shows the risk factors and neurological symptoms for all cases (age range, 23 to 86 years; mean, 58 ± 14 years; 8 women, 15 men). The most common syndrome was altered mental status in 22 cases (96%), which include 11 cases of hypersomnia (48%), 7 cases of coma (30%) and 4 cases of drowsiness (17%). Other characteristic included: vertical gaze palsy in 8 cases (35%), hypomnesis in 7 cases (30%), oculomotor nerve palsy in 7 cases (30%), disorientation in 5 cases (22%), barylalia and aphasia in 6 cases (26%), movement disorders in 9 cases (39%), ataxia in 5 cases (22%) and hemiplegia in 2 cases (9%).

Head CT of 22 patients with acute AOP infarctions performed 2 hours after the onset of symptoms showed no acute hemorrhage or ischemia, only one patient had bilateral parathalamic and rostral midbrain hypodensity (Fig. 3). One patient had bilateral paramedian thalamus and left anterior thalamus hypodensity at 24 hours after onset (Fig. 4). MR imaging showed characteristic asymmetricall bilateral paramedian thalamic in 30% (7/23) and symmetrical in 22% (5/23). Acute infarctions of paramedian thalamic and the rostral midbrain was present in 30% of patients (7/23), a distinct pattern of V-shaped hyperintensity on axial DWI along the pial surface of the midbrain in the interpeduncular fossa (Fig. 3) was found in 17% cases (4/23). Bilateral paramedian thalamic ischemia with anterolateral paramedian territory (Fig. 4) in 13% of patients (3/23). Bilateral paramedian thalamic infarction with left red nucleus (Fig. 5) in 4% of patient (1/23). None of the cases had a paramedian bithalamus and anterior thalamic with rostral midbrain. Stenosis or occlusion of the vertebral artery, basilar artery or P1-segments of PCA was observed in 5 patitens, whereas in 15 patients MRA was normal. CT perfusion image demonstrated symmetrically increased mean transit time (MTT) and decreased mean cerebral blood flow (CBF) and mean cerebral blood volume (CBV) in the bilateral paramedian thalami in the in 4 patients (Fig. 6). No bleeding signal was found in SWI of 4 patients.

All patients were followed up for 3 months upon discharge. MRS score was shown in Table 1. There were 65% cases of a favorable outcome (MRS score ≤ 2) who experienced a good functional recovery and could carry out daily life activities. Patients partially recovered normal mental status. Patient No.4 was full patient recovery. Patient No.1/2/6/10/13/15/18/19/20 of vertical ophthalmoplegia recovered in various degree. Patient No.3/10/19/23 had memory loss and patient No.5/11/19 had obvious recent memory decline. Patient No.7/8/16/22 had unclear articulation. Patient No.2/6/8/9/10/13/17/18/20/22 had dyskinesia. The patients with rostral midbrain infarction were dependent and unable to walk without assistance. Patient No.5/7/9/10/13/18/20 still had disorientation or mild ataxia symptoms.

Acute ischemia of AOP is uncommon, which accounted for 0.1–0.3% of all cerebral infarction [13, 14]. However, this is likely a conservative estimate due to the insufficient knowledge of it and limitations in the inclusion criteria [15]. AOP arising from P1 segments of the PCA supply predominantly paramedian bithalami with variable contribution to the rostral midbrain or anterolateral thalami [16]. In our studies, hypertension, smoking, diabetes mellitus, and hyperlipemia are risk factors for acute percheron infarction. Small vessel disease and arteriosclerosis are the causes of acute AOP infarcts in 14 patients (61%), which is similar to the previous reports [17]. It is indicated that cardioembolism is the most common cause [18], while only 7 cases (30%) had a potential source of cardiac embolism in our series. In addition, basilar artery dissection is seen in patient No.21 and 22. Atherosclerosis and small vessel disease are the main causes of acute AOP infarction.

Acute AOP ischemia has great variability with respect to symmetry, size, and territory, which is mainly due to the thalamic arteries vary between individuals. These differences are related to the parent vessel from which each branch arises, the number and position of the arteries and their tributaries [9, 12, 18]. 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. [19] presented mismatch between DWI and FLAIR mismatch 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. It is 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 [20]. 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 shows the presence of AOP, more often than not, the AOP is 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%) [21], 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) [22]. Then, paramedian arteries not only may supply the paramedian but also the anterior thalamic territories [11, 23], especially when the polar artery is absent (Fig. 2). 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 [23, 24], we also analysis the relationship between AOP infarction region and clinical presentation. Based on previous report,^{6, 9} 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 destroys these nuclei in different combinations and result in complex syndromes depending on which nuclei is involved [8]. 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 [25]. Disorder of consciousness in 22 cases, except patient No.15, may be due to involvement in the reticular activating system. Excitedly, recent evidences suggest that the paraventricular nuclei supplied the AOP is a key wakefulness-controlling nucleus in the thalamus [26]. 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, 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. The reason may be that the thalami have a vital role in cortical input processing to the RINMLF [17]. Memory dysfunctions are reported on patient No.3/5/9/10/11/19/23 (BPATI in patient No.5/11/19). The dorsomedial nucleus located in paramedian territory is supplied by the AOP, the mammillothalamic tract and anterior nucleus located in anterior territory is supplied by polar artery or AOP, which is usually related to memory function [27]. When the anterior thalamic territory is also involved, memory impairment is typically more severe [8]. In our series, patient No.5/11/19 with BPATI still have 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 is 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 is related to midbrain involvement [28]. The superior mesencephalic or rubral artery branch separately from P1 segment of the PCA or share a common origin with AOP, which supply 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 [29]. 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.

In this study, 65% of the patients have a favorable outcome. Complete recovery from bilateral paramedian thalamic infarction has occasionally been reported [8]. At present, the goal of acute AOP occlusion treatment is to promote recanalization [30]. Patient No.4/8/11/14/16/19 were treated with thrombolytic therapy without cerebral hemorrhage or edema on head CT within 6 hours. Patient No.4 recovered completely and the residual cognitive impairment disappeared (MRS score = 0). Patient No.8/11/14/16/19 were fully conscious with partial memory deficit (MRS score = 1). Thrombolytic therapy (time window < 4.5 h–6 h) is considered to be the most effective treatment for acute AOP infarction [31]. Our results are consistent with previous studies. Patients who are not suitable for thrombolysis beyond 6 hours received antiplatelet and heparin therapy. 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 is consistent with previous studies [10]. All 23 patients we reported took oral anticoagulants to prevent recurrence. According to the literature reports and our cases, we summarized the flow chart of the algorithm for the treatment of acute AOP infarction (Fig. 7).

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 [32], which should not be confused with AOP infarction (Fig. 8). A single large embolus at the basilar artery tip could mimic acute AOP infarction pattern, but it often accompanies with additional characteristic cerebellar, brainstem and occipital lobe infarcts. Deep venous infarction caused by thrombosis and diffuse midline gliomas do not involve the specific blood-supply territory of the AOP, but 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.

There are some limitations in thist study. Firstly, all the 23 patients were retrospectively enrolled from a single institution. Due to the limited sample size, large scale multicenter research is necessary in the future. Secondly, although many researchers believe that thrombolytic therapy is the first treatment option for acute AOP infarction, there are few cases of AOP occlusion recorded in this study. In our study, only 6 patients received thrombolytic therapy. The development of treatment protocols needs to be further improved through systematic case reports and clinical trials.