Phase I/II randomized controlled trial of autologous bone marrow-derived mesenchymal stem cell therapy for chronic stroke.

AIM: To examine the safety and efficacy of mesenchymal stem cell (MSC) therapy for intracerebral haemorrhage with neurological dysfunctions for a year. METHODS: MSC were ex vivo expanded from 29 mL (17-42 mL) autologous bone marrow. Patients were randomized to have two intravenous injections of autologous MSC or placebos in four weeks apart. Neurological functions and clinical outcomes were monitored before treatment and at 12th, 16th, 24th, 36th and 60th week upon completion of the treatment. RESULTS: A mean of 4.57 × 107 (range: 1.43 × 107-8.40 × 107) MSC per infusion was administered accounting to 8.54 × 105 (2.65 × 105-1.45 × 106) per kilogram body weight in two occasions. There was neither adverse event at time of administration nor sign of de novo tumour development among patients after monitoring for a year post MSC therapy. Neuro-restoration and clinical improvement in terms of modified Barthel index, functional independence measure and extended Glasgow Outcome Scale were evident among patients having MSC therapy compared to patients receiving placebos. CONCLUSION: Intravenous administration of autologous bone marrow-derived MSC is safe and has the potential of improving neurological functions in chronic stroke patients with severe disability.

Ticagrelor in Acute Stroke or Transient Ischemic Attack in Asian Patients: From the SOCRATES Trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes).

BACKGROUND AND PURPOSE: In the SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes), ticagrelor was not superior to aspirin. Because of differences in patient demographics and stroke disease pattern in Asia, outcomes of ticagrelor versus aspirin were assessed among Asian patients in a prespecified exploratory analysis. METHODS: Baseline demographics, treatment effects, and safety of ticagrelor and aspirin were assessed among Asian patients. Differences in outcomes between groups were assessed using Cox proportional hazard model. RESULTS: A total of 3858 (29.2%) SOCRATES participants were recruited in Asia. Among the Asian patients, the primary end point event occurred in 186 (9.6%) of the 1933 patients treated with ticagrelor, versus 224 (11.6%) of the 1925 patients treated with aspirin (hazard ratio, 0.81; 95% confidence interval, 0.67-0.99). The exploratory P value for treatment-by-region interaction was 0.27. The primary end point event rate in the Asian subgroup was numerically higher than that in the non-Asian group (10.6% versus 5.7%; nominal P<0.01). Among the Asian patients, the rate of PLATO (Platelet Inhibition and Patient Outcomes)-defined major bleeding was similar in the ticagrelor group and the aspirin group (0.6% versus 0.8%; hazard ratio, 0.76; 95% confidence interval, 0.36-1.61). CONCLUSIONS: The event rates were numerically higher in the Asian patients. Among the Asian patients with acute stroke or transient ischemic attacks, there was a trend toward a lower hazard ratio in reducing risk of the primary end point of stroke, myocardial infarction, or death in the ticagrelor group. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01994720.

Increasing pressure of external counterpulsation augments blood pressure but not cerebral blood flow velocity in ischemic stroke.

External counterpulsation (ECP) is a noninvasive method used to augment cerebral perfusion but the optimal use of ECP in ischemic stroke has not been well documented. We aimed to investigate the effects of ECP treatment pressure on cerebral blood flow and blood pressure (BP). We recruited 38 ischemic stroke patients with large artery occlusive disease and 20 elderly controls. We commenced ECP treatment pressure at 150 mmHg and gradually increased to 187.5, 225 and 262.5 mmHg. Mean cerebral blood flow velocities (CBFV) of bilateral middle cerebral arteries and continuous beat-to-beat BP were recorded before ECP and during each pressure increment for 3 minutes. Patient CBFV data was analyzed based on whether it was ipsilateral or contralateral to the infarct. Mean BP significantly increased from baseline in both stroke and control groups after ECP commenced. BP increased in both groups following raised ECP pressure and reached maximum at 262.5 mmHg (patients 16.9% increase versus controls 16.52%). The ipsilateral CBFV of patients increased 5.15%, 4.35%, 4.55% and 3.52% from baseline under the four pressures, respectively. All were significantly higher than baseline but did not differ among different ECP pressures; contralateral CBFV changed likewise. Control CBFV did not increase under variable pressures of ECP. ECP did increase CBFV of our patients to a roughly equal degree regardless of ECP pressure. Among the four ECP pressures tested, we recommend 150 mmHg as the optimal treatment pressure for ischemic stroke due to higher risks of hypertension-related complications with higher pressures.

Rituximab reduces attacks in Chinese patients with neuromyelitis optica spectrum disorders.

We evaluated the safety and efficacy of rituximab in seven Chinese patients with neuromyelitis optica (NMO) or neuromyelitis optica syndrome disorders (NMOSD) in a tertiary medical center in Hong Kong. After rituximab induction, five patients became relapse-free and two had 50% reduction of relapses over a median follow-up of 24 months. No further deterioration of functional status, measured by the Expanded Disability Status Scale, was observed in all patients. Infusions were well tolerated except in two patients who developed transient hypotension. Rituximab reduced clinical relapse and prevented neurological deterioration in a small cohort of Chinese patients with NMO or NMOSD.