Pontine infarction is usually manifested by classical crossed syndromes such as Millard-Gubler syndrome, Foville syndrome, Raymond-Cestan syndrome 1. These classical crossed pontine syndromes consist of ipsilateral peripheral cranial nerve palsies and contralateral movement disorders or sensory disturbances to the pontine lesions. However, some clinical observations have mentioned that pure motor hemiparesis (PMH) or hemiplegia can also be caused by pontine infarctions 2345678. In 1965, Fisher 3 firstly described the lacunar syndrome of PMH associated with the pontine lacunar infarction. Later, Kim and colleagues 6 studied 37 patients with unilateral pontine base infarctions, and found 17 of them had PMH. Nighoghossian et al 8 reported pontine infarction represented 28.5% (6/21) in all patients with PMH in an 1-year study. The majority of pontine infarcts with PMH or hemiplegia are lacunar lesions, but some of them are larger than 20 mm 69. Actually, in clinical practice, it is difficult to define the lesion location is in the pons or in the internal capsule-coronal radiate region only according to the early clinical manifestations of PMH or hemiplegia after stroke, especially in patients with negative brain computed tomography (CT) scans. Until now, the clinical and neuroimaging features, especially the details of magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) of pontine infarction patients with PMH or hemiplegia at early stage after stroke have not been well described. Moreover, the neurological deficits and prognosis have not been well investigated quantitatively. Therefore, in the present study, we prospectively observed the clinical and MRI(A) features, possible risk factors and prognosis of the patients of pontine infarction with PMH or hemiplegia, and compared them with those of capsule-coronal radiate region infarction who had similar clinical manifestations.

From May 1, 2002 to June 30, 2003, a total of 118 consecutive patients with the first-ever ischemic stroke were admitted to our stroke center within 6 hours after stroke onset. Among them, fifty patients fulfilled the inclusion criteria mentioned above, in which, 12 patients had pontine infarction and 38 patients had internal capsule-coronal radiate region infarction. MRI confirmed that the pontine infarction with PMH or hemiplegia accounted for 10.2% (12/118) of all first-ever ischemic stroke patients and 24% (12/50) of patients with PMH or hemiplegia who had acute negative brain CT.

The clinical features of patients with PMH or hemiplegia were compared between the pontine infarction patients and the internal capsule-coronal radiate region infarction patients (Table 1). None of the included 50 patients had hypoglycemia or orthostatic hypotension on admission. There were significant differences in the diabetes mellitus (50.0% vs 5.3%, P = 0.001), nonvertiginous dizziness at onset (58.3% vs 21.1%, P = 0.036) and a progressive course within 3 days after admission (33.3% vs 2.6%, P = 0.011) between the 2 groups.

Although early brain CT showed no lesion consistent with the main clinical signs (PMH or hemiplegia) in the 12 patients with pontine infarctions, MRI confirmed that an unilateral pontine infarction in 11 patients (8 patients in the left pons and 3 patients in the right pons) and bilateral pontine infarctions in only 1 patient (Figure 1, Table 2). All infarcts were located in the dorsal surface of the pons, with the longest diameter less than 15 mm in 4 patients, 15–20 mm in 6 patients, larger than 20 mm in 2 patients, and were longitudinal strip or patch in shape. MRA detected the atherosclerosis of intracranial arteries in 5 patients with pontine infarctions, and the large-vessel stenosis in 3 patients (Table 2). It was worth mentioning that although case 1 had pontine infarction extending to the midbrain (Figure 2), and case 6 had pontine infarction involving the level of the pontomedullary junction (Figure 3), both of them had no cranial nerve symptoms and signs consistent with the midbrain or medullary lesion.

All the patients with PMH or hemiplegia were followed up to 3 months after onset, except 2 patients in the internal capsule-coronal radiate region infarction group were lost. In the pontine infarction group, only 1 patient had a recurrent infarction at contralateral basal ganglia. BI ranges from 40 to 100 (median, 100), in which 100 in 9 cases, 70 in 2 cases, and 40 in 1 case, and mRS ranges from 0 to 4 grade (median, 1), in which grade 0 in 5 cases, grade 1 in 4 cases, and grade 3 in 2 cases, and grade 4 in 1 case. In the internal capsule-coronal radiate region infarction group, one patient died. BI also ranges from 40 to 100 (median, 100) and mRS ranges from 0 to 6 grade (median, 1). Although "a progressive course" is more frequent in pontine infarction patients with PMH (Table 1), there was no significant difference in outcomes between the PMH patients with pontine infarction and those with internal capsule-corona radiata infarction (P > 0.05). Among 3 of 4 pontine infarction patients with progressive courses, one's BI was 40 while the others' were both 70, and mRS were 3, 3, 4 receptively, there was a significant difference in bad outcome (mRS is equal or greater than 3) between the the pontine infracted patients with and without a progressive course (3/4 vs 0/8, P = 0.018).

In our a-year study, the pontine infarction with PMH or hemiplegia accounted for 10.2% (12/118) in all first-ever ischemic stroke patients and 24% (12/50) in patients who presented with both PMH or hemiplegia and acute negative CT scans, and lacunar infarcts with PMH or hemiplegia accounted for 42% (50/118) of all first-ever ischemic stroke patients. Arboix and colleagues 16 reported that pure motor hemiparesis accounted for 12.7% of all first-ever acute stroke patients, while lacunar infarcts were found in 85% of the pure motor hemiparesis patients and accounted for 23% of all acute stroke patients. The main reason for more patients with lacunar infarction and PMH in our study is more lacunars in Asian population. Li and colleagues 17 reported that 468 patients (67.0%) were classified as lacunar infarct according to the OCSP in 669 consecutive patients with acute ischemic stroke in Hong Kong. The other study reported that lacunar infarction accounts for 62% in 205 consecutive ethnic South Asian ischemic stroke patients 18. Another explanation for more patients with lacunar infarction and PMH in our study may be related to the way we selected the patients. Because the patients with first-ever ischemic stroke might undergo CT scan on admission and MRI(A) within 72 hours, some patients with too serious conditions to perform MRI(A) (e.g. malignant middle cerebral artery infarction or severe brain stem infarction) were excluded from this study. Our data suggest that the pontine infarction with PMH or hemiplegia is common in clinical practice. Although some previous studies have focused on the patients of pontine infarctions or posterior circulation infarctions and mentioned a few patients with PMH or hemiplegia among them, the clinical and neuroimaging features of pontine infarction with PMH or hemiplegia were not described in detail. The main findings of the previous studies are summarized in Table 3. In our study, all the 12 pontine infarction patients with PMH or hemiplegia had negative CT within 6 hours and positive MRI(A) within 72 hours after admission.

Until now, the exact risk factors and etiology for the pontine infarction are still unclear. Many previous studies reported that hypertension was the most important risk factor 25679. Other authors also found that diabetes was more frequently associated with lacunar infarctions. Arboix and colleagues' reports showed a increased occurrence of lacunar infarctions in diabetic patients, accompanied with a good prognosis 19. In the present study, we found that diabetes mellitus is more frequent in pontine infarction patients with PMH or hemiplegia. As we know, like hypertension, diabetes mellitus can cause the injuries of small arteries and arterioles 20, especially in the retina, kidney and brain (mainly in thalamus, internal capsule and pons) 21. Beside the penetrating arteries occlusion of paramedian or circumferential branches 6, some previous study also reported the high frequency of severe intracranial large-artery disease in posterior circulation infarctions including pontine infarctions 272223. A published study of 150 patients with acute isolated pontine infarctions showed that basilar artery branch disease (stenosis or occlusion, 39%) was the most etiology, followed by small-artery disease (21%) and cardioembolism (18%) 7. Chan and Silver 24 reported a patient of right ventral pontine infarction was due to basilar artery stenosis. Bassetti et al 2 also thought basilar artery branch disease was the most common etiology of isolated pontine infarctions in their study. Taken together with our data of MRI and MRA, it is possible that occlusion of paramedian branches might be the main cause of pontine infarction with PMH or hemiplegia, but intracranial large-artery disease can not be excluded.

In the present study, the clinical manifestations were very similar in both the patients with pontine infarctions and those with internal capsule-coronal radiate region infarctions. Therefore, it's difficult to distinguish them only depending on the clinical signs of PMH or hemiplegia at early stage of stroke, especially the patients who had no visible lesion on brain CT. Actually, it has been reported that even lacunar infarction is poorly predictable according to PMH within 12 hours of the stroke event 25. In this study, similar to diabetes mellitus, nonvertiginous dizziness at onset and a progressive course within 3 days after admission were also more frequently observed in the patients of pontine infarction with PMH or hemiplegia. It has been reported that diabetes mellitus is associated with a progressive course in ischemic stroke, increase infarct size and worsen stroke outcomes 22. However, there may be no obvious relationship between diabetes mellitus and nonvertiginous dizziness in this study, because none of our patients had orthostatic hypotension on admission, and the nonvertiginous dizziness here occurring at onset was different from the postural dizziness caused by autonomic neuropathy of diabetes mellitus, the later is often accompanied with orthostatic hypotension and may last for a long time unless it was treated specially 26. Therefore, the clinical features of pontine infarctions with PMH or hemiplegia might be associated with nonvertiginous dizziness at onset, a progressive course within 3 days after admission and the history of diabetes mellitus.

As we know, MRI is more sensitive and specific than CT to identify the infarcts location of ischemic stroke at early stage after onset, especially to detect small or pontine lesions 257827. Moulin and colleagues studied 100 patients with ataxic hemiparesis after first stroke, and found that the most common location of lesions were the internal capsule (39%), followed by the pons (19%). There were 14% of their patients had no visible lesion on brain CT, and MRI was performed in 23 patients and confirmed the location of the lesion in half of CT negatives 27. In our study, acute brain CT was not able to find any lesion consistent with the main clinical signs in the 12 patients of pontine infarctions with PMH or hemiplegia, but MRI confirmed that the diameter for the majority of the pontine infarctions was smaller than 20 mm, and all of infarcts located in the dorsal surface of the pons, an anatomic area in which the pyramidal tract passes through, but preserving protuberance calote in which the nuclei of the cranial pairs are located. MRA showed intracranial arteries atherosclerosis in 5 patients and a large-vessel stenosis in 3 patients, which suggests MRA may provide more information for the possible etiology of pontine infarctions.

Most of the previous studies showed a good short-term prognosis in the patients with lacunar infarctions in pons 2728. In the present study, we observed a good short-term prognosis in the patients of pontine infarctions with PMH or hemiplegia in a 3-month follow-up. Although "a progressive course" is more frequent in pontine infarction patients with PMH, there was no significant difference in outcomes between the PMH patients with pontine infarction and those with internal capsule-corona radiata infarction. However, compared to those without a progressive course, the pontine infracted patients with a progressive course had a bad outcome. Further investigations are needed to evaluate the long-term prognosis in more patients of the pontine infarction with PMH or hemiplegia.

This study suggests that the pontine infarction with PMH or hemiplegia is a common clinical situation, which is worth receiving more attention. This subtype of pontine infarction patients might manifest PMH or hemiplegia, with nonvertiginous dizziness, a progressive course and the history of diabetes mellitus being more frequently. Though no visible lesion on brain CT on admission, MRI can confirm the infarct location in the basal pons at early stage after stroke onset.

LL acquired data, performed statistical analysis, analyzed and interpreted data, and wrote and critically revised the manuscript. LZ acquired data, performed statistical analysis, analyzed and interpreted data. JZ designed and the study, obtained funding, performed the statistical analysis, interpreted the results and critically revised the manuscript. SL, SZ and JY assisted with the data collection. ZY assessed the CT and MR images. All authors read and approved the final manuscript.