The physiological and pathophysiological roles of copper in the nervous system.

Copper is a critical trace element in biological systems due the vast number of essential enzymes that require the metal as a cofactor, including cytochrome c oxidase, superoxide dismutase and dopamine-ß-hydroxylase. Due its key role in oxidative metabolism, antioxidant defence and neurotransmitter synthesis, copper is particularly important for neuronal development and proper neuronal function. Moreover, increasing evidence suggests that copper also serves important functions in synaptic and network activity, the regulation of circadian rhythms, and arousal. However, it is important to note that because of copper's ability to redox cycle and generate reactive species, cellular levels of the metal must be tightly regulated to meet cellular needs while avoiding copper-induced oxidative stress. Therefore, it is essential that the intricate system of copper transporters, exporters, copper chaperones and copper trafficking proteins function properly and in coordinate fashion. Indeed, disorders of copper metabolism such as Menkes disease and Wilson disease, as well as diseases linked to dysfunction of copper-requiring enzymes, such as SOD1-linked amyotrophic lateral sclerosis, demonstrate the dramatic neurological consequences of altered copper homeostasis. In this review, we explore the physiological importance of copper in the nervous system as well as pathologies related to improper copper handling.

Oocyte cryopreservation and reciprocal in vitro fertilization in a transgender man on long term testosterone gender-affirming hormone therapy: a case report.

Objective: To report a successful case of oocyte cryopreservation and subsequent in vitro fertilization (IVF) in a transgender male receiving continued testosterone gender-affirming hormone therapy, followed by reciprocal embryo transfer (ET). Design: A case report of a rare case of fertility preservation in a transgender man with concomitant use of testosterone therapy for 4 years before and during ovarian stimulation. Setting: Private fertility clinic with university affiliation. Patients: A 26-year-old transgender man undergoing oocyte cryopreservation before gender-affirming surgery. Interventions: Fertility preservation using oocyte cryopreservation and IVF with reciprocal fresh ET into a cisfemale partner. Main Outcome Measures: Successful oocyte cryopreservation, oocyte thawing, and reciprocal IVF cycle. Results: Oocyte cryopreservation of 29 mature oocytes. Sixteen mature oocytes survived the thaw, and 12 were fertilized with intracytoplasmic sperm injection. A fresh ET of an advanced blastocyst resulted in a clinical pregnancy and live birth. Conclusions: Fertility preservation with oocyte cryopreservation or IVF with embryo cryopreservation is feasible for patients on continued long-term testosterone gender-affirming therapy. Future studies on egg quality and reproductive outcomes are required. Our case report demonstrates a promising outcome in this patient population.

Live birth rates after resolution of endometrial cavity fluid in frozen embryo transfer cycles.

RESEARCH QUESTION: Are live birth rates affected in frozen embryo transfer cycles that develop transient endometrial cavity fluid that resolves by day of embryo transfer? DESIGN: The first frozen blastocyst transfer cycle between January 1st, 2016 and December 31st, 2019 were included in this retrospective cohort study at an academic fertility center. The presence or absence of endometrial cavity fluid (ECF) detected on initial ultrasound and at time of transfer was recorded. Patients who had persistent ECF at time of transfer were excluded from the study. The primary outcome was live birth rate in the group with resolved ECF relative to the group without ECF. RESULTS: A total of 1034 frozen blastocyst transfer cycles were included, 54 with resolved ECF and 980 without ECF. Adjusted analyses were performed using a log-binomial regression model. Live birth rates were 35.2% and 34.2%, adjusted risk ratio 1.00 [95% CI 0.70-1.50] in the two groups, respectively. CONCLUSION: Live birth rates in frozen embryo transfer cycles are equivalent between patients with resolved endometrial cavity fluid compared to those who never had endometrial cavity fluid. Our findings suggest that the presence of endometrial cavity fluid is likely not detrimental to live birth rates if the fluid spontaneously resolves by the time of embryo transfer.

Copper induces neuron-sparing, ferredoxin 1-independent astrocyte toxicity mediated by oxidative stress.

Copper is an essential enzyme cofactor in oxidative metabolism, anti-oxidant defenses, and neurotransmitter synthesis. However, intracellular copper, when improperly buffered, can also lead to cell death. Given the growing interest in the use of copper in the presence of the ionophore elesclomol (CuES) for the treatment of gliomas, we investigated the effect of this compound on the surround parenchyma-namely neurons and astrocytes in vitro. Here, we show that astrocytes were highly sensitive to CuES toxicity while neurons were surprisingly resistant, a vulnerability profile that is opposite of what has been described for zinc and other toxins. Bolstering these findings, a human astrocytic cell line was similarly sensitive to CuES. Modifications of cellular metabolic pathways implicated in cuproptosis, a form of copper-regulated cell death, such as inhibition of mitochondrial respiration or knock-down of ferredoxin 1 (FDX1), did not block CuES toxicity to astrocytes. CuES toxicity was also unaffected by inhibitors of apoptosis, necrosis or ferroptosis. However, we did detect the presence of lipid peroxidation products in CuES-treated astrocytes, indicating that oxidative stress is a mediator of CuES-induced glial toxicity. Indeed, treatment with anti-oxidants mitigated CuES-induced cell death in astrocytes indicating that oxidative stress is a mediator of CuES-induced glial toxicity. Lastly, prior induction of metallothioneins 1 and 2 in astrocytes with zinc plus pyrithione was strikingly protective against CuES toxicity. As neurons express high levels of metallothioneins basally, these results may partially account for their resistance to CuES toxicity. These results demonstrate a unique toxic response to copper in glial cells which contrasts with the cell selectivity profile of zinc, another biologically relevant metal.

Evaluation of Early Frozen Blastocyst Transfer in A True Natural Cycle Protocol in Comparison to A Hormone Replacement Protocol: A Single-Center Cohort Study.

OBJECTIVE: Timing of frozen embryo transfer (FET) within a purported window of implantation is of increasing interest, and there is a paucity of evidence surrounding the transfer of frozen embryos early within these frozen embryo transfer protocols. This study aimed to evaluate whether live birth rates were equivalent after FET of blastocysts 4 days after luteinizing hormone (LH) surge in a true natural cycle protocol, compared to a hormone replacement (HR) protocol. MATERIALS AND METHODS: Single-centre, retrospective cohort study involving patients undergoing autologous frozen blastocyst transfer from January 1st, 2013, to December 31st, 2016. Cycles were grouped according to their protocol: true natural cycle (hormonal detection of LH surge with FET scheduled four days later) versus HR cycle (luteal phase gonadotropin-releasing hormone agonist suppression, oral or vaginal estradiol and intramuscular progesterone starting five days before FET). A total of 850 cycles were included, 501 true natural cycles and 349 HR cycles. The primary outcome was the live birth rate, secondary outcomes included clinical pregnancy rate and miscarriage. Logbinomial regression models were performed adjusting for a priori selected variables. RESULTS: Adjusted resulted in live birth rates of 38.7 and 40.4%, [adjusted risk ratio (aRR): 0.96, 95% confidence interval (CI): 0.76-1.22, P=0.729] in the natural cycle and HR groups, respectively. The secondary outcome analyses did not demonstrate any statistically significant difference in the rate of positive human chorionic gonadotropin (hCG), clinical intrauterine pregnancy rate, or miscarriage rate. CONCLUSION: The timing of the FET four days after LH surge in a true natural cycle protocol results in equivalent live birth rates compared to a HR protocol. Results of this study suggest that the window of implantation within the natural cycle may be less finite than currently believed and further prospective studies evaluating the timing of frozen embryo transfer are warranted.

Comparative Embryo Development Outcomes following Extending Embryo Culture to Day 6: A Retrospective Cohort Study.

BACKGROUND: Past studies have shown that culturing slow-growing embryos from day 5 to day 6 may increase vitrification yield. This study aims to evaluate if the proportion of embryos eligible for vitrification increases by growing embryos not vitrified by day 5 to day 6. MATERIALS AND METHODS: In this retrospective cohort study, a Canadian tertiary-care clinic-based cohort was identified between August 2019 and December 2020. In vitro fertilization (IVF) cycles involving autologous oocytes with at least one viable day 5 embryo were selected for inclusion. We compared embryo developmental outcomes of IVF cycles performed before and after an embryo cryopreservation policy change. Prior to March 2020, good-quality day 5 blastocysts of any stage were eligible for vitrification, and after that date, good-quality expanded blastocysts on either day 5 or day 6 were eligible. The primary outcome is the comparative proportion of embryos eligible for vitrification. The secondary outcome is to identify embryo, maternal and cycle factors that are predictive of day 6 vitrification. RESULTS: A total of 3,438 viable embryos across 679 consecutive IVF cycles were included in this study. After the policy change, we found similar mean proportions of blastocysts eligible for cryopreservation (46.9% per IVF cycle in group 2 vs. 44.4% in group 1, mean difference 0.025, 95% confidence interval -0.021 to 0.071, P=0.28). The mean number of cryopreserved embryos were significantly higher in group 2 (mean 2.2 vs. 1.7 embryos, P=0.007). Factors that predicated an embryo's progression to day 6 included: younger age of egg provider, presence of an early blastocyst on day 5, and cycles involving surgically-retrieved sperm. CONCLUSION: A cryopreservation policy change to include good-quality full and expanded day 6 blastocysts while avoiding to vitrify early blastocysts on day 5 yielded comparable proportions of embryos eligible for vitrification per IVF cycle.

Microglial reprogramming by Hv1 antagonism protects neurons from inflammatory and glutamate toxicity.

Although the precise mechanisms determining the neurotoxic or neuroprotective activation phenotypes in microglia remain poorly characterized, metabolic changes in these cells appear critical for these processes. As cellular metabolism can be tightly regulated by changes in intracellular pH, we tested whether pharmacological targeting of the microglial voltage-gated proton channel 1 (Hv1), an important regulator of intracellular pH, is critical for activated microglial reprogramming. Using a mouse microglial cell line and mouse primary microglia cultures, either alone, or co-cultured with rat cerebrocortical neurons, we characterized in detail the microglial activation profile in the absence and presence of Hv1 inhibition. We observed that activated microglia neurotoxicity was mainly attributable to the release of tumor necrosis factor alpha, reactive oxygen species, and zinc. Strikingly, pharmacological inhibition of Hv1 largely abrogated inflammatory neurotoxicity not only by reducing the production of cytotoxic mediators but also by promoting neurotrophic molecule production and restraining excessive phagocytic activity. Importantly, the Hv1-sensitive change from a pro-inflammatory to a neuroprotective phenotype was associated with metabolic reprogramming, particularly via a boost in NADH availability and a reduction in lactate. Most critically, Hv1 antagonism not only reduced inflammatory neurotoxicity but also promoted microglia-dependent neuroprotection against a separate excitotoxic injury. Our results strongly suggest that Hv1 blockers may provide an important therapeutic tool against a wide range of inflammatory neurodegenerative disorders.

Intracellular zinc signaling influences NMDA receptor function by enhancing the interaction of ZnT1 with GluN2A.

Zinc, loaded into glutamate-containing presynaptic vesicles and released into the synapse in an activity-dependent manner, modulates neurotransmission through its actions on postsynaptic targets, prominently via high-affinity inhibition of GluN2A-containing NMDA receptors. Recently, we identified a postsynaptic transport mechanism that regulates endogenous zinc inhibition of NMDARs. In this new model of zinc regulation, the postsynaptic transporter ZnT1 mediates zinc inhibition of NMDARs by binding to GluN2A. Through this interaction, ZnT1, a transporter that moves zinc from the cytoplasm to the extracellular domain, generates a zinc microdomain that modulates NMDAR-mediated neurotransmission. As ZnT1 expression is transcriptionally driven by the metal-responsive transcription factor 1 (MTF-1), we found that intracellular zinc strongly drives MTF-1 in cortical neurons in vitro and increases the number of GluN2A-ZnT1 interactions, thereby enhancing tonic zinc inhibition of NMDAR-mediated currents. Importantly, this effect is absent when the interaction between GluN2A and ZnT1 is disrupted by a cell-permeable peptide. These results suggest that zinc-regulated gene expression can dynamically regulate NMDAR-mediated synaptic processes.

NUP62 localizes to ALS/FTLD pathological assemblies and contributes to TDP-43 insolubility.

A G4C2 hexanucleotide repeat expansion in the C9orf72 gene is the most common genetic cause of ALS and FTLD (C9-ALS/FTLD) with cytoplasmic TDP-43 inclusions observed in regions of neurodegeneration. The accumulation of repetitive RNAs and dipeptide repeat protein (DPR) are two proposed mechanisms of toxicity in C9-ALS/FTLD and linked to impaired nucleocytoplasmic transport. Nucleocytoplasmic transport is regulated by the phenylalanine-glycine nucleoporins (FG nups) that comprise the nuclear pore complex (NPC) permeability barrier. However, the relationship between FG nups and TDP-43 pathology remains elusive. Our studies show that nuclear depletion and cytoplasmic mislocalization of one FG nup, NUP62, is linked to TDP-43 mislocalization in C9-ALS/FTLD iPSC neurons. Poly-glycine arginine (GR) DPR accumulation initiates the formation of cytoplasmic RNA granules that recruit NUP62 and TDP-43. Cytoplasmic NUP62 and TDP-43 interactions promotes their insolubility and NUP62:TDP-43 inclusions are frequently found in C9orf72 ALS/FTLD as well as sporadic ALS/FTLD postmortem CNS tissue. Our findings indicate NUP62 cytoplasmic mislocalization contributes to TDP-43 proteinopathy in ALS/FTLD.

A Practical Approach to Fertility Considerations in Endometriosis Surgery.

Endometriosis surgery requires thoughtful consideration and planning for those with infertility or those who wish to conceive in the future. Clinical history, examination, imaging, and fertility assessment can help plan, prepare and provide goal-directed surgical interventions when required. Further understanding of the benefits and limitations of surgery on future fertility outcomes is essential for those who provide care for patients with endometriosis. Endometriosis is a prevalent gynecologic condition, especially among patients with infertility. Studies demonstrate that, from a fertility perspective, surgery for endometriosis likely has a beneficial impact on the chance of spontaneous conception; however, selecting the appropriate surgical candidate can be challenging. To make a fully informed decision with regard to surgery, it is important to determine the patient's fertility goals and to conduct a thorough workup. Among patients with endometriosis-related infertility, first-line-assisted reproductive technology (ART) is generally preferred over surgery. Specific consideration in cases of minimal or mild endometriosis, ovarian endometrioma(s), and deep endometriosis (DE) are required for targeted counseling. Patients with symptoms significantly impacting their quality of life (QOL), or indications to proceed with surgery (ie, risk of malignancy, organ obstruction, or dysfunction) are best managed with surgical care by an experienced team. Surgery should be considered cautiously given the risks of damage to ovarian reserve, adhesions, and surgical complications. Risk of damage to ovarian reserve is a particularly important consideration among patients with endometrioma(s), with or without low ovarian reserve, and surgical complications are especially prevalent among patients undergoing surgery for bowel endometriosis. Goal-directed surgical treatment, as opposed to the traditional perspective of complete disease eradication, may be of particular importance among selected patients whereby fertility is a priority.

Time-lapse KIDScoreD5 for prediction of embryo pregnancy potential in fresh and vitrified-warmed single-embryo transfers.

RESEARCH QUESTION: Can KIDScoreD5 predict which blastocysts have the highest potential for achieving pregnancy? DESIGN: A retrospective cohort study of 670 single fresh or frozen (FET) embryo transfer cycles was conducted between May 2019 and June 2021 at the Ottawa Fertility Centre, Canada. Blastocysts obtained from stimulated eligible cycles and cultured in a time-lapse incubator were selected for transfer or cryopreservation based on Gardner morphological scoring. Implantation and viable pregnancy rates were analysed retrospectively using KIDScoreD5 and Gardner scores associated with the transferred embryos. The predictive power of the KIDScoreD5 and Gardner assessment was evaluated using the average area under the curve (AUC) of the receiver operating characteristic curve. RESULTS: KIDScoreD5 was positively correlated with implantation (r = 0.96, P = 0.002) and viable pregnancy (r = 0.96, P  = 0.0001) rates. In fresh embryo transfer cycles, the AUC for implantation rate was significantly higher for KIDScoreD5 compared with Gardner scoring (0.70 versus 0.63, P  = 0.03). For FET, significantly higher AUC were calculated for KIDScoreD5 than for Gardner scoring, for both implantation (0.64 versus 0.54, P  = 0.002) and viable pregnancy (0.63 versus 0.53, P  = 0.002) rates. When the ranking of cryopreserved embryos was based on KIDScoreD5, 46.2% of the FET cycles had at least one unused sibling embryo with a better KIDScoreD5 than the one selected for FET based on Gardner assessment. CONCLUSIONS: KIDScoreD5 predicts implantation and viable pregnancy rates of blastocysts better than Gardner morphological assessment in single fresh or cryopreserved embryo transfer cycles.

Local translation in primary afferents and its contribution to pain.

ABSTRACT: Chronic pain remains a significant problem due to its prevalence, impact, and limited therapeutic options. Progress in addressing chronic pain is dependent on a better understanding of underlying mechanisms. Although the available evidence suggests that changes within the central nervous system contribute to the initiation and maintenance of chronic pain, it also suggests that the primary afferent plays a critical role in all phases of the manifestation of chronic pain in most of those who suffer. Most notable among the changes in primary afferents is an increase in excitability or sensitization. A number of mechanisms have been identified that contribute to primary afferent sensitization with evidence for both increases in pronociceptive signaling molecules, such as voltage-gated sodium channels, and decreases in antinociceptive signaling molecules, such as voltage-dependent or calcium-dependent potassium channels. Furthermore, these changes in signaling molecules seem to reflect changes in gene expression as well as posttranslational processing. A mechanism of sensitization that has received far less attention, however, is the local or axonal translation of these signaling molecules. A growing body of evidence indicates that this process not only is dynamically regulated but also contributes to the initiation and maintenance of chronic pain. Here, we review the biology of local translation in primary afferents and its relevance to pain pathobiology.

Reduced live birth rates after embryo transfer in patients with prior cesarean delivery: A retrospective cohort study.

OBJECTIVE: To evaluate whether live birth rates following first embryo transfer (ET) among patients after cesarean delivery are lower compared to patients with only prior vaginal delivery. STUDY DESIGN: Retrospective cohort study including patients with prior delivery who underwent first subsequent embryo transfer (fresh or frozen) between January 2013 and September 2019. The primary outcome was live birth rate among patients with at least one prior cesarean delivery compared to vaginal delivery only. Secondary outcomes included positive serum hCG, clinical intrauterine pregnancy and miscarriage rates. We performed a subgroup analysis with the cesarean delivery group based on labour status at the time of delivery. We fit a multivariable log-binomial regression model. RESULTS: Total of 962 patients met inclusion criteria: 351 in the cesarean delivery group and 611 in the vaginal delivery group. Live birth rate was significantly lower in the cesarean delivery group compared to vaginal delivery group at 30.0% vs 36.9% [aRR 0.81, 95% CI 0.67-0.98]. We also found lower positive hCG [aRR 0.82, 95% CI 0.72-0.94] and clinical pregnancy [aRR 0.85, 95% CI 0.73-0.99]. There was no significant difference in miscarriage rate. A subgroup analysis within the cesarean delivery group in active labour demonstrated significantly lower live birth rates compared to the vaginal delivery group [aRR 0.67, 95% CI 0.49-0.92]. CONCLUSIONS: Live birth rates following first ET were significantly lower after cesarean delivery compared to vaginal delivery. These findings may be largely attributable to a subgroup of patients with prior cesarean delivery in active labour who may be at particular risk of reduced live birth rates after ET.

Imprecision in Precision Medicine: Differential Response of a Disease-Linked GluN2A Mutant to NMDA Channel Blockers.

Mutations in N-methyl-d-aspartate receptors (NMDAR) subunits have been implicated in a growing number of human neurodevelopmental disorders. Previously, a de novo mutation in GRIN2A, encoding the GluN2A subunit, was identified in a patient with severe epilepsy and developmental delay. This missense mutation, which leads to GluN2A-P552R, produces significant dendrotoxicity in transfected rodent cortical neurons, as evidenced by pronounced dendritic blebbing. This injurious process can be prevented by treatment with the NMDA antagonist memantine. Given the increasing use of FDA approved NMDA antagonists to treat patients with GRIN mutations, who may have seizures refractory to traditional anti-epileptic drugs, we investigated whether additional NMDA antagonists were effective in attenuating neurotoxicity associated with GluN2A-P552R expression. Intriguingly, we found that while treatment with memantine can effectively block GluN2A-P552R-mediated dendrotoxicity, treatment with ketamine does not, despite the fact that both drugs work as open NMDAR channel blockers. Interestingly, we found that neurons expressing GluN2A-P552R were more vulnerable to an excitotoxic insult-an effect that, in this case, could be equally rescued by both memantine and ketamine. These findings suggest that GluN2A-P552R induced dendrotoxicity and increased vulnerability to excitotoxic stress are mediated through two distinct mechanisms. The differences between memantine and ketamine in halting GluN2A-P552R dendrotoxicity could not be explained by NMDA antagonist induced changes in MAP or Src kinase activation, previously shown to participate in NMDA-induced excitotoxicity. Our findings strongly suggest that not all NMDA antagonists may be of equal clinical utility in treating GRIN2A-mediated neurological disorders, despite a shared mechanism of action.

Oocyte cryopreservation in a transgender man on long-term testosterone therapy: a case report.

OBJECTIVE: To report a case of ovarian stimulation for the purposes of oocyte cryopreservation in a transgender man without cessation of long-term testosterone therapy. DESIGN: Report of a unique case of fertility preservation through ovarian stimulation and oocyte cryopreservation in a transgender man who had been on testosterone therapy for 18 months before treatment. The patient elected to continue testosterone therapy throughout ovarian stimulation and oocyte retrieval. To our knowledge, there have not been any published reports of patients undergoing oocyte cryopreservation while continuing long-term testosterone therapy. SETTING: Private fertility clinic with university affiliation. PATIENTS: A 20-year-old transgender man undergoing oocyte cryopreservation before gonadectomy. INTERVENTIONS: Fertility preservation through oocyte cryopreservation. MAIN OUTCOME MEASURES: This patient had a robust response to ovarian gonadotropin stimulation. Leuprolide acetate was used for final oocyte maturation to minimize ovarian hyperstimulation syndrome risk. RESULTS: Cryopreservation of 22 mature oocytes. CONCLUSIONS: Cryopreservation of mature oocytes is possible for patients on continued long-term testosterone therapy. The impact of long-term testosterone therapy on markers of ovarian reserve, reproductive potential, and long-term reproductive outcomes have yet to be elucidated and further studies are needed in this area.

The Multifaceted Roles of Zinc in Neuronal Mitochondrial Dysfunction.

Zinc is a highly abundant cation in the brain, essential for cellular functions, including transcription, enzymatic activity, and cell signaling. However, zinc can also trigger injurious cascades in neurons, contributing to the pathology of neurodegenerative diseases. Mitochondria, critical for meeting the high energy demands of the central nervous system (CNS), are a principal target of the deleterious actions of zinc. An increasing body of work suggests that intracellular zinc can, under certain circumstances, contribute to neuronal damage by inhibiting mitochondrial energy processes, including dissipation of the mitochondrial membrane potential (MMP), leading to ATP depletion. Additional consequences of zinc-mediated mitochondrial damage include reactive oxygen species (ROS) generation, mitochondrial permeability transition, and excitotoxic calcium deregulation. Zinc can also induce mitochondrial fission, resulting in mitochondrial fragmentation, as well as inhibition of mitochondrial motility. Here, we review the known mechanisms responsible for the deleterious actions of zinc on the organelle, within the context of neuronal injury associated with neurodegenerative processes. Elucidating the critical contributions of zinc-induced mitochondrial defects to neurotoxicity and neurodegeneration may provide insight into novel therapeutic targets in the clinical setting.

Pneumomyelia Secondary to Interlaminar Cervical Epidural Injection Causing Acute Cord Injury with Transient Quadriparesis.

BACKGROUND: Cervical radiculopathy and cervicalgia are commonly managed with spinal epidural steroid injections in the outpatient setting. Although cervical epidural injections are routinely performed, there is potential for significant complications if proper technique and safety measures are not followed. Spinal cord infarction and stroke following transforaminal injection have been described in the literature, whereas interlaminar injections have been associated with both epidural hematomas and direct cord injury. CASE DESCRIPTION: Here we describe a case of pneumomyelia after cervical interlaminar epidural steroid injection resulting in acute quadriparesis. The patient's symptoms were caused by an inadvertent puncture of the cervical cord and injection of air present in the needle or syringe via an interlaminar approach. The initial computed tomography imaging showed a slit-like lesion at C7-T2 with density consistent with air that migrated rostrally on a follow-up scan. CONCLUSIONS: Epidural steroid injections are often the treatment of choice in management of neck pain and cervical radiculopathy. Devastating complications can ensue if proper safety measures and technique are not used during the procedure regardless of the approach used.

Infection of arachnoid cyst associated with vasospasm and stroke in a pediatric patient: case report.

Arachnoid cysts are relatively common and benign intraarachnoid membrane outpouchings containing CSF-like fluid. The majority of arachnoid cysts remain stable and asymptomatic and do not require intervention in the pediatric population. Here, the authors present the first reported case of an infected arachnoid cyst in a pediatric patient resulting in severe vasospasm of the left terminal internal carotid artery, left A1 segment, and left M1 branches with a left middle cerebral artery infarct. Their experience suggests that close monitoring is warranted for this condition and that the pediatric population may be at higher risk for vasospasm.