Modulation of dendritic spine remodeling in the motor cortex following spinal cord injury: effects of environmental enrichment and combinatorial treatment with transplants and neurotrophin-3

Incomplete spinal cord injury (SCI) elicits structural plasticity of the spared motor system, including the motor cortex, which may underlie some of the spontaneous recovery of motor function seen after injury. Promoting structural plasticity may become an important component of future strategies to improve functional outcomes. We have recently observed dynamic changes in the density and morphology of dendritic spines in the motor cortex following SCI. The present study sought to test whether SCI-induced changes in spine density and morphology could be modulated by potential strategies to enhance functional recovery. We examined the effects of enriched environment, transplants, and neurotrophin-3 on the plasticity of synaptic structures in the motor cortex following SCI. Housing rats in an enriched environment increased spine density in the motor cortex regardless of injury. SCI led to a more slender and elongated spine morphology. Enriched housing mitigated the SCI-induced morphological alterations, suggesting that the environmental modification facilitates maturation of synaptic structures. Transplantation of embryonic spinal cord tissue and delivery of neurotrophin-3 at the injury site further increased spine density when combined with enriched housing. This combinatorial treatment completely abolished the injury-induced changes, restoring a preinjury pattern of spine morphology. These results demonstrated that remodeling of dendritic spines in the motor cortex after SCI can be modulated by enriched housing, and the combinatorial treatment with embryonic transplants and neurotrophin-3 can potentiate the effects of enriched housing. We suggest that synaptic remodeling processes in the motor cortex can be targeted for an intervention to enhance functional recovery after SCI.     

MR imaging findings suggestive of posterior reversible encephalopathy syndrome in adolescents with systemic lupus erythematosus

Background

Endothelial damage, hypertension and cytotoxic medications may serve as risk factors for the posterior reversible encephalopathy syndrome (PRES) in systemic lupus erythematosus. There have been few case reports of these findings in pediatric lupus patients.

Objective

We describe clinical and neuroimaging findings in children and adolescents with lupus and a PRES diagnosis.

Materials and methods

We identified all clinically acquired brain MRIs of lupus patients at a tertiary care pediatric hospital (2002–2008). We reviewed clinical features, conventional MRI and diffusion-weighted imaging (DWI) findings of patients with gray- and white-matter changes suggestive of vasogenic edema and PRES.

Results

Six pediatric lupus patients presenting with seizures and altered mental status had MRI findings suggestive of PRES. In five children clinical and imaging changes were seen in conjunction with hypertension and active renal disease. MRI abnormalities were diffuse and involved frontal regions in five children. DWI changes reflected increased apparent diffusivity coefficient (unrestricted diffusion in all patients). Clinical and imaging changes significantly improved with antihypertensive and fluid management.

Conclusion

MRI changes suggestive of vasogenic edema and PRES may be seen in children with active lupus and hypertension. The differential diagnosis of seizures and altered mental status should include PRES in children, as it does in adults.     

Feasibility of extracorporeal photopheresis in pediatric patients with graft‐versus‐host disease after hematopoietic stem cell transplantation

Graft‐versus‐host disease (GVHD) is a main cause of morbidity and mortality following hematopoietic stem cell transplantation. The cumulative incidence of acute and chronic GVHD (aGVHD, cGVHD) reaches 30%‐50% and 20% in pediatric populations, respectively. Prednisolone and/or calcineurin inhibitors (CNI) are first‐line treatments, but no superior second‐line treatment has yet been established. Several treatments have been suggested, among others extracorporeal photopheresis (ECP). Technical advances have made treatment of pediatric patients possible; however, only few reports on the feasibility of ECP in children have been published. We retrospectively studied the feasibility, safety, and efficacy of ECP in 15 children with steroid‐dependent/refractory acute or chronic GVHD, who initiated ECP treatment between April 2014 and January 2018. Only few and mild side effects directly related to the ECP procedure were registered, even in patients with low body weight. The most frequent cause of shortened or canceled ECP treatment was difficulties with vascular accesses, which were more rarely seen using central venous catheters with larger lumens and made of stiffer material. Nine patients had grade II‐III aGVHD. Six of these experienced a response to ECP at day 28, while eight of nine had responded at the last ECP treatment. Six patients had cGVHD when ECP was initiated, and of these, four had a partial response at last ECP treatment. We found ECP to be a feasible and safe treatment, and particularly, children with aGVHD appeared to respond well to ECP.     

Loperamide Toxicity Revealing Apical Hypertrophic Cardiomyopathy

Loperamide, a μ-opioid receptor agonist, can cause cardiotoxicity by inhibiting the potassium ion channel and slowing cardiomyocyte repolarization. This, in turn, can lead to frequent early afterdepolarizations, the most common mechanism of drug-induced long QT syndrome and torsades de pointes. Apical hypertrophic cardiomyopathy (AHCM) is a nonobstructive hypertrophic cardiomyopathy rarely associated with malignant arrhythmias. We present a case of loperamide-induced malignant ventricular arrhythmia revealing underlying AHCM in a 25-year-old woman with a history of sudden cardiac arrest (SCA) and opioid use.It is important to evaluate for structural heart disease in all patients presenting with SCA, regardless of presumed etiology such as drug-induced cardiotoxicity, to prevent missed opportunities for adequate treatment. Furthermore, the diagnosis of AHCM in SCA warrants further genetic evaluation for variances with a predilection for malignant arrhythmias.