Glen Jickling

Circulating endothelial progenitor cells and age-related white matter changes

Background and Purpose— The objective was to evaluate the relationship between circulating endothelial progenitor cells (EPC) and age-related white matter changes (ARWMC). Endothelial dysfunction plays a role in the development of ARWMC. EPC incorporate into sites endothelial damage and are thought to be involved in the repair of vascular risk factor induced endothelial injury. ARWMC can be evaluated using CT or MRI. Methods— In 172 individuals, circulating EPC were defined by the surface markers CD31 and von Willebrand factor. ARWMC were rated on CT scan using the ARWMC scale and divided into 3 groups based on ARWMC scale score (ARWMC score 0 [none], score 1–10 [mild-to-moderate], score >10 [severe]). Severity of ARWMC was correlated with levels of EPC and vascular risk factors. Results— On univariate analysis, EPC were found to be significantly lower in patients with severe ARWMC (P=0.01). ARWMC were also associated with hypertension (P<0.001), age (P<0.001), creatinine clearance (P=0.031), C-reactive protein (P<0.001), and use of angiotensin-converting enzyme or angiotensin receptor blocker (P=0.004). Multiple logistic regression analysis identified EPC level, age, hypertension, and hypertriglyceridemia as significant independent predictors of severe ARWMC. Conclusions— Levels of circulating EPC were significantly lower in patients with severe ARWMC. Other variables significantly associated with severe ARWMC were age, hypertension, and hypertriglyceridemia. Further study is required to delineate the pathophysiological relationship between EPC, vascular risk factors, and ARWMC.

Acetaminophen toxicity with concomitant use of carbamazepine

Acetaminophen is a widely used analgesic that can cause acute liver failure when consumed above a maximum daily dose. Certain patients may be at increased risk of hepatocellular damage even at conventional therapeutic doses. We report a case of a 34-year-old man on carbamazepine for complex partial seizures who developed acute liver and renal failure on less than 2.5 grams a day of acetaminophen. This raises caution that patients on carbamazepine should avoid chronic use of acetaminophen, and if required use at lower doses with vigilant monitoring for signs of liver damage.

Mobile stroke unit triage of patients with a suspected stroke: a novel solution to reducing suspected stroke admissions in busy emergency departments

Background Evaluation of patients with a suspected stroke is one of the most common neurological emergencies requiring rapid, comprehensive assessment by the stroke service to determine patient eligibility for timely reperfusion therapies. Prehospital evaluation may help to improve patient selection and reduce avoidable admissions to overcapacity emergency departments. Methods and results We report on our early experience of prehospital triage of patients with a suspected stroke using a mobile stroke unit (MSU) equipped with CT scanner in rural Alberta. During the initial 4 months of operation, 28 patients were evaluated by the team in the MSU. Eight patients were within the time window of thrombolysis and were treated with intravenous tissue plasminogen activator in the MSU. No patients suffered haemorrhage or any other complications. Fourteen patients with multiple aetiologies (stroke mimics 6, transient ischaemic attacks 2, subacute stroke outside thrombolysis window 2, intracranial haemorrhage 3 and cerebral contusion 1) were assessed in the field and transferred to the tertiary hospital. Six patients after assessment and imaging were repatriated back to the local hospital as they were deemed stroke mimics or were outside of the reperfusion window. Conclusions The MSU offers a novel approach to performing timely evaluation and treatment of patients with a suspected stroke in rural settings and may help reduce admissions to overcapacity tertiary care facilities.

MicroRNA-based therapeutics in central nervous system injuries

Central nervous system (CNS) injuries, such as stroke, traumatic brain injury (TBI) and spinal cord injury (SCI), are important causes of death and long-term disability worldwide. MicroRNA (miRNA), small non-coding RNA molecules that negatively regulate gene expression, can serve as diagnostic biomarkers and are emerging as novel therapeutic targets for CNS injuries. MiRNA-based therapeutics include miRNA mimics and inhibitors (antagomiRs) to respectively decrease and increase the expression of target genes. In this review, we summarize current miRNA-based therapeutic applications in stroke, TBI and SCI. Administration methods, time windows and dosage for effective delivery of miRNA-based drugs into CNS are discussed. The underlying mechanisms of miRNA-based therapeutics are reviewed including oxidative stress, inflammation, apoptosis, blood–brain barrier protection, angiogenesis and neurogenesis. Pharmacological agents that protect against CNS injuries by targeting specific miRNAs are presented along with the challenges and therapeutic potential of miRNA-based therapies.

Left vertebral artery dissection causing bilateral internuclear ophthalmoplegia

A 21-year-old woman presented to the emergency department 1 day after a fall. On the day of presentation, she awoke with horizontal diplopia and posterior neck pain. Based on clinical findings, she was diagnosed with bilateral internuclear ophthalmoplegia. A conventional angiogram identified a left vertebral artery dissection. She was started on anticoagulant therapy, with gradual improvement of her diplopia over several months. Diplopia is frequently seen in the emergency department. Internuclear ophthalmoplegia is a cause of binocular diplopia and is important to recognize because it indicates a brainstem lesion requiring neurologic evaluation.