Brivaracetam-Associated Rhabdomyolysis Requiring Renal Replacement Therapy: A Case Report and Review of the Literature.

Rhabdomyolysis is a rare adverse reaction that has a previously established association with levetiracetam use, which selectively binds the synaptic vesicle glycoprotein 2A (SV2A). Its structural analogue, brivaracetam, is a new third-generation antiseizure medication that has a higher affinity for SV2A, and current data suggests it provides a more favorable adverse event profile. Here, however, we report a case of rhabdomyolysis requiring dialysis in which serum creatine kinase level increased rapidly for several days until brivaracetam was discontinued. The delayed creatine kinase peak, rapid decline upon discontinuation of brivaracetam, and prior association of rhabdomyolysis with levetiracetam strongly suggest a causal relationship. To date, there are three reported cases of brivaracetam-associated rhabdomyolysis in the food and drugs administration adverse event reporting system (FAERS). Despite its favorable side effects profile, the use of brivaracetam may be associated with life-threatening rhabdomyolysis.

CGRP as a potential mediator for the sexually dimorphic responses to traumatic brain injury.

BACKGROUND: The outcomes of traumatic brain injury (TBI) exhibit variance contingent upon biological sex. Although female sex hormones exert neuroprotective effects, the administration of estrogen and progesterone has not yielded conclusive results. Hence, it is conceivable that additional mediators, distinct from female sex hormones, merit consideration due to their potential differential impact on TBI outcomes. Calcitonin gene-related peptide (CGRP) exhibits sexually dimorphic expression and demonstrates neuroprotective effects in acute brain injuries. In this study, we aimed to examine sex-based variations in TBI structural and functional outcomes with respect to CGRP expression. METHODS: Male and female Sprague Dawley rats were exposed to controlled cortical impact to induce severe TBI, followed by interventions with and without CGRP inhibition. In the acute phase of TBI, the study centered on elucidating the influence of CGRP on oxidative stress, nuclear factor erythroid 2-related factor 2 (Nrf2) and endothelial nitric oxide synthase (eNOS) signaling in the peri-impact tissue. Subsequently, during the chronic phase of TBI, the investigation expanded to evaluate CGRP expression in relation to lesion volume, microvascular dysfunction, and white matter injury, as well as working and spatial memory, anxiety-like, and depression-like behaviors in subjects of both sexes. RESULTS: Female rats exhibited elevated levels of CGRP in the peri-impact brain tissue during both baseline conditions and in the acute and chronic phases of TBI, in comparison to age-matched male counterparts. Enhanced CGRP levels in specific brain sub-regions among female rats correlated with superior structural and functional outcomes following TBI compared to their male counterparts. CGRP inhibition induced heightened oxidative stress and a reduction in the expression of Nrf2 and eNOS in both male and female rats, with the observed alteration being more pronounced in females than in males. CONCLUSIONS: This study marks the inaugural identification of CGRP as a downstream mediator contributing to the sexually dimorphic response observed in TBI outcomes.

Investigating sex disparities in traumatic brain injury (TBI) is crucial for the advancement of precision therapeutics. Despite the neuroprotective effects demonstrated by female sex hormones, the administration of estrogen and progesterone has not produced conclusive results. Therefore, it is conceivable that additional mediators, separate from female sex hormones, warrant consideration due to their potential differential influence on TBI outcomes. In this study, we examined sex-related variations in calcitonin gene-related peptide (CGRP) expression in peri-impact brain tissue and investigated its potential implications on associated TBI outcomes. CGRP exhibits sexually dimorphic expression and exerts a multifaceted influence on diverse physiological processes that contribute to the pathophysiology of TBI. Our findings reveal that female rats exhibit heightened CGRP levels at both baseline and post-TBI within specific brain sub-regions, thereby contributing to superior structural and functional outcomes compared to their age-matched male counterparts. Additionally, we identified substantial sex-based variations in mechanisms modulated by CGRP pertaining to oxidative stress and microvascular dysfunction. The disparities in CGRP levels may be crucial for comprehending the advantageous outcomes noted in female TBI. Therefore, elucidating the sex-related distinctions in CGRP within TBI brains could pave the way for improved management and treatment strategies for TBI in both male and female individuals.

Superficial Temporal Artery-to-Middle Cerebral Artery Bypass in Ischemic Stroke With Blood Pressure-Dependent Symptoms.

The efficacy of extracranial-intracranial (EC-IC) bypass in preventing ischemic stroke progression and recurrence is controversial. As per the current hypothesis, EC-IC bypass is most beneficial for patients with persistent hemodynamic insufficiency. Hence, various approaches have been used to evaluate hemodynamic insufficiency, including repeated single photon emission CT (SPECT) imaging or continuous monitoring of cerebral flow with transcranial Doppler ultrasound (TCD). However, both modalities are time- and resource-intensive. In this report, we discuss how EC-IC bypass turned out to be beneficial for a patient presenting with blood pressure-dependent severe aphasia and right hemiparesis due to middle cerebral artery (MCA) occlusion that failed thrombectomy. CT perfusion (CTP) scan at admission demonstrated a persistent volume of delayed perfusion without core infarct. Following the superficial temporal artery-to-middle cerebral artery (STA-MCA) bypass, the patient's National Institute of Health Stroke Scale (NIHSS) score improved from 12 to 1. Ischemic penumbra, as seen on CTP imaging, also improved after the STA-MCA bypass. Our case suggests that persistent volume of delayed perfusion and blood pressure-dependent neurological deficits can be used in tandem as selection criteria for EC-IC bypass.

Antenatally diagnosed intraspinal-posterior mediastinal neurenteric cyst - what is the optimal management?

Neurenteric cyst is a rare congenital anomaly that belongs to the spinal dysraphism spectrum. It is classically a disease of late childhood, with some rare reports of intrauterine and adult presentation. The increase in incidental antenatal diagnosis raises new management questions. We present a case of an asymptomatic combined intraspinal-posterior mediastinal neurenteric cyst. The cyst was diagnosed on antenatal ultrasound and was initially treated with image-guided aspiration in early infancy. However, the cyst recurred and the patient developed recurrent episodes of bacterial meningitis. Two-stage surgical resection was performed, although the infection prohibited complete excision. We caution against image guided aspiration of neurenteric cysts, and suggest a management algorithm based on the available literature.

Salvage therapy for vagal nerve stimulator infection; Literature review and report of a delayed recurrence.

BACKGROUND: Vagal Nerve Stimulation (VNS) is one of the most common neuro-modulation based approaches for the treatment of medically intractable epilepsy. Despite advances in technology and surgical techniques, hardware infection remains a recognized and feared complication in VNS placement. Management of such infections is scarce in the literature with the majority of data available in case reports. It ranges from immediate removal of the VNS device to conservative treatment with antibiotics in an attempt to salvage the device, particularly in patients who demonstrated significant improvement in seizure frequency and quality of life. METHODS: We performed a review of the literature in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to identify reported cases of salvaged VNS infection. A literature search for relevant English articles was conducted using Medline. References of relevant articles were also reviewed. Articles that comprised an attempt to salvage an infected VNS were included. RESULTS: We obtained 12 articles describing an attempt to salvage an infected VNS. Out of a total of 62 reported VNS infections and 43 salvage attempts using a variety of antibiotic-based approaches, 17 cases were successfully salvaged and 26 cases failed the salvage attempt and had to be explanted eventually. Moreover, we report a case of an 18-year-old male with Lennox-Gastaut syndrome who presented21 days after VNS placement with a MRSA deep tissue infection. An attempt was made to treat the infection with long-term culture-based intravenous antibiotics, but it recurred three years later with neck wound dehiscence and positive wound culture for the same organism, and ex-plantation was thus performed. CONCLUSION: The management of VNS infections remains a dilemma for neurosurgeons. Although the idea of salvaging an infected VNS seems appealing, hardware removal seems to be inevitable despite adequate antibiotic treatment.

Role of connexins in spinal cord injury: An update.

Connexins (Cxs) are a family of transmembrane proteins that assemble into groups of six, forming what is known as a connexon or a hemichannel. Connexins are named based on their molecular weight, e.g. Cx43 is the connexin protein that weighs 43 kDa. Two hemichannels, each from a different cell, can link up end-to-end forming a gap junction. In the nervous system, gap junctions facilitate metabolite exchange between neighboring cells, in addition to electrical and chemical impulses. Many animal studies have been conducted to investigate the role of different types of Cxs in spinal cord injury (SCI) - most notably Cx43 - and the potential for targeting them with inhibitors. In this review, the authors discuss these studies and provide an update on recent connexin specific pharmacological agents that may potentially pave the way for the use of connexin inhibition in the management of SCI in humans, if more translational studies are done.