Neuromyelitis Optica Spectrum Disorder with Sick Sinus Syndrome: Two Cases and a Literature Review.

BACKGROUND AND OBJECTIVE: Neuromyelitis optica spectrum disorder (NMOSD) is a rare immune-mediated demyelinating disease of the central nervous system (CNS). There is a lack of reports of sick sinus syndrome (SSS) associated with NMOSD; thus, we hereby report two cases of patients with NMOSD who developed SSS. CASES PRESENTATION: The patients were both male and presented with area postrema syndrome. Brain MRI showed lesions in the dorsal part of their medulla oblongata. They were diagnosed with NMOSD when aquaporin-4 antibodies were found in their serum. Slow heart rates and several episodes of syncope were also observed in case 1 during hospitalization, while Holter monitoring showed sinus pauses (10-11 s) and SSS was diagnosed. A pacemaker was fitted. Case 2 had a respiratory arrest followed by a subsequent cardiac arrest. He was successfully resuscitated with epinephrine injection and cardiopulmonary resuscitation. Through immunotherapy, their neurological functions became stable and heart rate and blood pressure returned to the baseline. CONCLUSIONS: Since sick sinus syndrome is a life-threatening complication, serious heart arrhythmias should be considered as a potential result of area postrema syndrome associated with NMOSD.

New asymptomatic thrombosis caused by carotid web during the acute period of cerebral infarction.

BACKGROUND: At present, the carotid web (CaW) as an important cause of cryptogenic ischemic stroke has gradually received clinical attention. CaW is associated with a high risk of stroke and patient is more likely to have recurrent stroke if the CaW is untreated. We report a patient who developed CaW related thrombosis during the acute period of cerebral infarction. CASE PRESENTATION: A 49-year-old male patient with CaW in the left internal carotid artery was diagnosed by computed tomography angiography (CTA) and had two cerebral infarctions in two years. Within 72 h after thrombolysis for an acute cerebral infarction, acute thrombosis was identified between the web and the posterior wall of the carotid artery on carotid ultrasound. Emergent carotid endarterectomy (CEA) was performed to remove abnormal CaW structures and thrombosis to prevent stroke. The patient recovered well and was asymptomatic at 2 months follow-up. CONCLUSION: Carotid web related thromboembolism is a rare cause of stroke. Carotid ultrasound plays an important role in the diagnosis of asymptomatic thrombosis caused by carotid web. Carotid endarterectomy is effective for stroke prevention in patient with carotid web related thrombosis.

The Acid Sphingomyelinase Inhibitor Amitriptyline Ameliorates TNF-α-Induced Endothelial Dysfunction.

PURPOSE: Inflammation associated endothelial cell (EC) dysfunction is key to atherosclerotic disease. Recent studies have demonstrated a protective role of amitriptyline in cardiomyocytes induced by hypoxia/reoxygenation. However, the mechanism by which amitriptyline regulates the inflammatory reaction in ECs remains unknown. Thus, the aim of this study was to investigate whether amitriptyline protects against inflammation in TNF-α-treated ECs. METHODS: HUVECs were incubated with amitriptyline (2.5 µM) or TNF-α (20 ng/ml) for 24 h. EdU, tube formation, transwell, DHE fluorescence staining, and monocyte adhesion assays were performed to investigate endothelial function. Thoracic aortas were isolated from mice, and vascular tone was measured with a wire myograph system. The levels of ICAM-1, VCAM-1, MCP-1, phosphorylated MAPK and NF-κB were detected using western blotting. RESULTS: Amitriptyline increased the phosphorylation of nitric oxide synthase (eNOS) and the release of NO. Amitriptyline significantly inhibited TNF-α-induced increases in ASMase activity and the release of ceramide and downregulated TNF-α-induced expression of proinflammatory proteins, including ICAM-1, VCAM-1, and MCP-1 in ECs, as well as the secretion of sICAM-1 and sVCAM-1. TNF-α treatment obviously increased monocyte adhesion and ROS production and impaired HUVEC proliferation, migration and tube formation, while amitriptyline rescued proliferation, migration, and tube formation and decreased monocyte adhesion and ROS production. Additionally, we demonstrated that amitriptyline suppressed TNF-α-induced MAPK phosphorylation as well as the activity of NF-κB in HUVECs. The results showed that the relaxation response of aortic rings to acetylcholine in the WT-TNF-α group was much lower than that in the WT group, and the sensitivity of aortic rings to acetylcholine in the WT-TNF-α group and WT-AMI-TNF-α group was significantly higher than that in the WT-TNF-α group. CONCLUSION: These results suggest that amitriptyline reduces endothelial inflammation, consequently improving vascular endothelial function. Thus, the identification of amitriptyline as a potential strategy to improve endothelial function is important for preventing vascular diseases.

Retrospective Observation of Low-Dose Rituximab Treatment in Chinese Patients With Neuromyelitis Optica Spectrum Disorders in a Real-World Setting.

Objective: This study aimed to investigate the efficacy and safety of low-dose rituximab (RTX) in the treatment of neuromyelitis optica spectrum disorders (NMOSD) patients. Methods: NMOSD patients were treated with RTX at ~25% of the standard dose. The annualized relapse rate (ARR), expanded disability status scale (EDSS) score, visual function system scale (VFSS) and length of spinal cord lesions before and after treatment were statistically compared. The dynamic changes in the proportion of CD19+ B lymphocytes after treatment were monitored, and adverse reactions were recorded. Results: In total, 36 NMOSD patients who received a low-dose RTX treatment (375-mg/m2 induction dose and 500 mg every 6 months) were recruited. The mean follow-up time after the RTX treatment was 19.83 ± 7.74 months. After the treatment, the ARR decreased from 1.97 ± 1.93 to 0.12 ± 0.32, the EDSS score decreased from 3.43 ± 1.49 to 3.10 ± 1.88, and the spinal cord lesion length decreased from 5.54 ± 3.96 to 4.31 ± 3.73. These differences were all statistically significant. The subgroup analysis of the patients who had previously received non-steroidal immunosuppressants (NSISs) (n = 20) showed that after the RTX treatment, the ARR decreased from 0.66 ± 0.51 to 0.08 ± 0.26, the EDSS score decreased from 3.65 ± 1.22 to 3.40 ± 1.99, and the spinal cord lesion length decreased from 5.68 ± 3.73 to 4.21 ± 3.58. These differences were all statistically significant. The VFSS scores did not show a significant change. The Kaplan-Meier analysis showed that low-dose RTX significantly delayed recurrence, which was also observed in the subgroup analysis of patients who previously received NSISs. Five relapses in 5 cases were noted after the low-dose RTX administration, and the percentage of CD19+ B cells remained < 1% in 3 cases during relapse. During the RTX treatment and subsequent follow-up, 8 (22.2%) patients reported adverse reactions, all of which were minor. Conclusion: Low-dose RTX is an effective and safe treatment method for NMOSDs. This method is worth popularizing in developing countries or regions, especially in areas where RTX is not covered by medical insurance.

Evaluating team-based, lecture-based, and hybrid learning methods for neurology clerkship in China: a method-comparison study.

BACKGROUND: Neurology is complex, abstract, and difficult for students to learn. However, a good learning method for neurology clerkship training is required to help students quickly develop strong clinical thinking as well as problem-solving skills. Both the traditional lecture-based learning (LBL) and the relatively new team-based learning (TBL) methods have inherent strengths and weaknesses when applied to neurology clerkship education. However, the strengths of each method may complement the weaknesses of the other. Combining TBL with LBL may produce better learning outcomes than TBL or LBL alone. We propose a hybrid method (TBL + LBL) and designed an experiment to compare the learning outcomes with those of pure LBL and pure TBL. METHODS: One hundred twenty-seven fourth-year medical students attended a two-week neurology clerkship program organized by the Department of Neurology, Sun Yat-Sen Memorial Hospital. All of the students were from Grade 2007, Department of Clinical Medicine, Zhongshan School of Medicine, Sun Yat-Sen University. These students were assigned to one of three groups randomly: Group A (TBL + LBL, with 41 students), Group B (LBL, with 43 students), and Group C (TBL, with 43 students). The learning outcomes were evaluated by a questionnaire and two tests covering basic knowledge of neurology and clinical practice. RESULTS: The practice test scores of Group A were similar to those of Group B, but significantly higher than those of Group C. The theoretical test scores and the total scores of Group A were significantly higher than those of Groups B and C. In addition, 100% of the students in Group A were satisfied with the combination of TBL + LBL. CONCLUSIONS: Our results support our proposal that the combination of TBL + LBL is acceptable to students and produces better learning outcomes than either method alone in neurology clerkships. In addition, the proposed hybrid method may also be suited for other medical clerkships that require students to absorb a large amount of abstract and complex course materials in a short period, such as pediatrics and internal medicine clerkships.