The Clinical Conundrum of Managing Ischemic Stroke in Patients with Immune Thrombocytopenia.

Guidelines are lacking for management of acute ischemic stroke and stroke prevention in patients with immune thrombocytopenia (ITP). Our aim is to highlight the dilemma inherent in managing patients with both significant bleeding and thrombotic risk factors. In this review, we present two patients with history of ITP who presented with acute ischemic stroke and received tissue plasminogen activator (tPA) and endovascular thrombectomy (EVT), a rare management strategy in this patient population. In addition, we identified 27 case reports of ischemic stroke in patients with ITP; none of them received tPA or EVT. Furthermore, there are 92 patients with significant thrombocytopenia with no available data regarding the cause of thrombocytopenia, who were acutely treated with tPA or EVT. Conclusive evidence cannot be determined based on these limited number of cases. Future multicenter prospective cohort studies in patients with ITP are needed to provide better evidence-based treatment plans. At present, treatment of acute ischemic stroke in patients with ITP requires close collaboration between hematology and vascular neurology experts to find a balance between the benefit and risk of hemorrhagic complications.

Case Report: COVID-19 Infection and Cervical Artery Dissection.

A 45-year-old woman presented 3 days after symptom resolution from a COVID-19 infection with a left vertebral artery dissection with no known preceding trauma or underlying disposition. She subsequently suffered a left lateral medullary stroke 15 hours after her initial presentation. Cervical artery dissections (CeAD) can occur in the absence of trauma, and in some cases, infection may be a contributing factor. COVID-19 infection can cause an endotheliopathy and inflammatory response, which may contribute to intimal vessel disruption. Whether COVID-19 infection can contribute to CeAD and subsequent stroke is discussed, along with other considerations regarding the pathogenesis of CeAD.

Can osmotic demyelination syndrome be a complication of liver failure?

This case demonstrates that osmotic demyelination syndrome (ODS) can occur in absence of hyponatremia in patients with fulminant liver failure and markedly high bilirubin levels. Extremely high bilirubin levels, such as >900 µmol/L in the case presented here, may lead to blood brain barrier dysfunction by disrupting blood vessel endothelial cell function as well as increase the release of inflammatory cytokines. As demonstrated in the case here, even small fluctuations in electrolytes may make the brain increasingly more vulnerable to ODS. Clinicians should keep ODS high on their differential even in eunatremic patients with liver failure who have decreased levels of consciousness or coma.

A BRCA1-Dependent DNA Damage Response in the Regenerating Adult Peripheral Nerve Milieu.

It is not generally appreciated that DNA repair machinery has a critical role in the remodeling of neurons that adopt a regenerative phenotype. We identified that breast cancer 1 (BRCA1)-dependent DNA activity, previously well known to repair cancer cells, is active in adult peripheral neurons and Schwann cells during their injury and regeneration response. Temporary or partial loss of BRCA1 or blockade of its intraneuronal nuclear entry impaired outgrowth in neurons in vitro and impacted nerve regeneration and functional recovery in vivo. We found that distal axonal injury triggered a BRCA1-dependent DNA damage response (DDR) signal in neuronal soma. BRCA1 also supported an enabling transcriptional program of injured neurons and supporting Schwann cells. Our findings indicate that BRCA1 offers prominent functional roles in neurons and glial cells including key support for their physical and molecular integrity. Since BRCA1 mutations are common in humans, this function of BRCA1 in peripheral neurons and their glial partners warrants attention.

Enhancing adult nerve regeneration through the knockdown of retinoblastoma protein.

Tumour suppressor pathways may offer novel targets capable of altering the plasticity of post-mitotic adult neurons. Here we describe a role for the retinoblastoma (Rb) protein, widely expressed in adult sensory neurons and their axons, during regeneration. In adult sensory neurons, Rb short interfering RNA (siRNA) knockdown or Rb1 deletion in vitro enhances neurite outgrowth and branching. Plasticity is achieved in part through upregulation of neuronal PPARυ; its antagonism inhibits Rb siRNA plasticity, whereas a PPARυ agonist increases growth. In an in vivo regenerative paradigm following complete peripheral nerve trunk transection, direct delivery of Rb siRNA prompts increased outgrowth of axons from proximal stumps and entrains Schwann cells to accompany them for greater distances. Similarly, Rb siRNA delivery following a nerve crush improves behavioural indices of motor and sensory recovery in mice. The overall findings indicate that inhibition of tumour suppressor molecules has a role to play in promoting adult neuron regeneration.