Hongbing Chen

Lesion patterns and mechanism of cerebral infarction caused by severe atherosclerotic intracranial internal carotid artery stenosis.

BACKGROUND AND PURPOSE The lesion patterns and mechanisms of ischemic stroke caused by extracranial internal carotid artery (EICA) stenosis are well understood. The prognosis of intracranial internal carotid artery (IICA) stenosis is very poor. However, little is known about lesion patterns and mechanisms of cerebral infarcts caused by IICA stenosis. The objective of this study was to investigate the lesion patterns and mechanisms of infarcts produced by severe IICA stenosis and compare it with that produced by severe EICA stenosis. METHODS We recruited 62 patients with acute cerebral infarcts who fulfilled the following criteria: 1) lesions of acute infarcts were verified by diffusion-weighted imaging (DWI) performed within 1 week of stroke onset; 2) infarct lesions were located within the territory of unilateral internal carotid artery (ICA); 3) infarcts were definitely caused by severe atherosclerosis stenosis (stenosis rate of 70%-99%) of the ipsilateral IICA or EICA, with all other potential causes of stroke being entirely excluded. According to the distributions of infarct lesions in the arterial territory of the ICA displayed on DWI, lesion patterns were classified as either 1) single infarct [perforating artery infarct (PAI), pial artery infarct (PI) or border-zone infarct (BZI)], or 2) multiple infarcts (a combination of types described above). RESULTS There were 29 patients with ischemic stroke caused by severe IICA stenosis, and 33 patients with stroke caused by severe EICA stenosis. Single BZI (14/29, P=0.015), and infarcts involving the border zone (19/29, P=0.021) or the internal border zone (13/29, P=0.013) were identified more often in patients with IICA stenosis compared to those with EICA stenosis. PI and/or PAI (22/32, P=0.021) were identified more often in patients with EICA stenosis. CONCLUSIONS Lesion patterns in patients with severe IICA stenosis were different from those with severe EICA stenosis. The hypoperfusion mechanism leading to BZI was more important for patients with severe IICA stenosis than for those with severe EICA stenosis. Embolisms leading to PI and/or PAI were more important for patients with severe EICA stenosis.

Intracranial versus Extracranial Symptomatic Carotid Atherosclerosis in Chinese Patients: Risk Factors, Stroke Mechanisms, and Long-Term Prognosis

OBJECTIVES This study aims to investigate the clinical-radiological features and stroke mechanisms of symptomatic intracranial internal carotid artery (IICA) atherosclerosis and prognoses of patients with IICA atherosclosis, and compare these data with those from patients with symptomatic extranial carotid artery (EICA) atherosclerosis. METHODS We prospectively recruited 155 patients with symptomatic IICA or EICA atherosclerosis (stenosis ≥50% or occlusion) from 1968 Chinese patients with a first-ever ischemic stroke or transient ischemic attack. The patients were followed up for stroke recurrence, cardiovascular events, and death. RESULTS There were 80 and 75 patients in the IICA and EICA groups, respectively. Multivariate logistic regression analyses showed that the patients in the IICA group were associated with hypertension (odds ratio [OR], 5.980; 95% confidence interval [CI], 1.790-19.976) and asymptomatic intracranial atherosclerosis (OR, 2.564; 95% CI, 1.222-5.377), while the patients in the EICA group were associated with smoking (OR, 2.397; 95% CI, 1.150-4.998) and contralateral EICA disease (OR, 4.742; 95% CI, 1.455-15.455). Hemodynamic stroke alone was more common in the IICA group; artery-to-artery embolism was identified more often in the EICA group (P <.05). The cumulative incidences of ipsilateral stroke recurrence, stroke recurrence and cardiovascular events, and death at 5 years were 43.5%, 52.4%, and 27.3%, respectively, in the patients of the IICA group, which did not differ from those of the EICA group. CONCLUSIONS IICA atherosclerosis as well as EICA atherosclerosis is an important cause of stroke in Chinese patients. Patients with symptomatic IICA atherosclerosis had unique clinical-radiological features and stroke mechanisms compared with those with symptomatic EICA atherosclerosis; their long-term prognosis was poor.

Increased spontaneous neuronal activity in structurally damaged cortex is correlated with early motor recovery in patients with subcortical infarction.

Secondary cortical thinning and volumetric atrophy in the motor‐related cortex can inhibit early functional recovery after subcortical infarction. However, the relationship between the spontaneous neuronal activity in these cortices and motor recovery in patients with focal cerebral infarct remains unknown.

Autonomic Neuropathy and Albuminocytologic Dissociation in Cerebrospinal Fluid As the Presenting Features of Primary Amyloidosis: A Case Report

Objective Primary amyloidosis is a disease with a poor prognosis and multi-organ involvement. Here, we report the clinical and pathological features of a patient with primary amyloidosis featuring autonomic neuropathy as the initial symptom and albuminocytologic dissociation in the cerebrospinal fluid (CSF). Methods The patient was a 60-year-old Chinese male with numbness, orthostatic hypotension, and gastrointestinal symptoms. For diagnosis, we performed an electromyogram (EMG), lumbar puncture, Bence Jones protein urine test, serum electrophoresis blood test, sural nerve and rectal membrane biopsies, transthyretin (TTR) gene sequencing, and bone marrow puncture. Results Congo red staining of sural nerve and rectal membrane biopsies showed amyloid deposition and apple-green birefringence was visualized under polarized light microscopy. TTR gene sequencing showed no causative mutation. Following lumbar puncture, normal CSF cell counts and elevated CSF protein concentration (1,680 mg/L) were detected. Bone marrow puncture showed that out of the total number of whole blood cells, 0.56% were abnormal plasma cells and that 87.4% of the total number of plasma cells were abnormal. EMG results showed mixed peripheral nerve damage predominately in the sensory nerve fibers. Conclusion Obvious symptoms of neuropathy, particularly autonomic neuropathy, albuminocytologic dissociation, and organ function damage suggested a diagnosis of amyloidosis. In such patients, neurologists should use caution to differentiate between chronic inflammatory demyelinating polyneuropathy, primary amyloidosis, and familial amyloid neuropathy.

Unfolded protein response is activated in the ipsilateral thalamus following focal cerebral infarction in hypertensive rats

Focal cerebral cortical infarction causes secondary neurodegeneration in the remote regions, such as the ventroposterior nucleus of the thalamus. Retrograde degeneration of thalamocortical fibers is considered as the principle mechanism, but the exact molecular events remain to be elucidated. This study aimed to investigate whether unfolded protein response (UPR) is activated in thalamic neurons following distal middle cerebral artery occlusion (MCAO) in stroke‐prone renovascular hypertensive rats. Immunostaining and immunoblotting were performed to evaluate the expression of Grp78 and its downstream effectors in the thalamus at 3, 7 and 14 days after MCAO. Secondary thalamic degeneration was assessed with Nissl staining and NeuN immunostaining. Neuronal death was not apparent at 3 days post‐ischaemia but was evident in the thalamus at 7 and 14 days after MCAO. Grp78 level was reduced in the ipsilateral thalamus at 3 and 7 days after MCAO. In parallel, phosphorylated eIF2α and ATF4 levels were elevated, indicating the activation of UPR. In contrast, ATF6α and CHOP levels were not changed. These results suggest that UPR is activated before neuronal death in the ipsilateral thalamus after MCAO and may represent a key early event in the secondary thalamic degeneration.