Molecular Biology of Brain Metastasis

Metastasis to the central nervous system (CNS) remains a major cause of morbidity and mortality in patients with systemic cancer. As the length of survival in patients with systemic cancer improves, thanks to multimodality therapies, focusing on metastases to the CNS becomes of paramount importance. Unique interactions between the brain’s micro-environment, blood-brain barrier, and tumor cells are hypothesized to promote distinct molecular features in CNS metastases that may require tailored therapeutic approaches. This review will focus on the pathophysiology, epigenetics, and immunobiology of brain metastases in order to understand the metastatic cascade. Cancer cells escape the primary tumor, intravasate into blood vessels, survive the hematogenous dissemination to the CNS, arrest in brain capillaries, extravasate, proliferate, and develop angiogenic abilities to establish metastases. Molecular biology, genetics, and epigenetics are rapidly expanding, enabling us to advance our knowledge of the underlying mechanisms involved. Research approaches using cell lines that preferentially metastasize in vivo to the brain and in vitro tissue-based studies unfold new molecular leads into the disease. It is important to identify and understand the molecular pathways of the metastatic cascade in order to target the investigation and development of more effective therapies and research directions

Reappraisal of Pediatric Normal-Pressure Hydrocephalus

While normal-pressure hydrocephalus (NPH) is most commonly diagnosed in older adulthood, a significant body of literature has accumulated over half a century documenting the clinical phenomenon of an NPH-like syndrome in pediatric patients. As in adult NPH, it is likely that pediatric NPH occurs due to a heterogeneous array of developmental, structural, and neurodegenerative pathologies, ultimately resulting in aberrant cerebrospinal fluid (CSF) flow and distribution within and around the brain. In this review, we aimed to systematically survey the existing clinical evidence supporting the existence of a pediatric form of NPH, dating back to the original recognition of NPH as a clinically significant subtype of communicating hydrocephalus. Leveraging emergent trends from the old and more recent published literature, we then present a modern characterization of pediatric NPH as a disorder firmly within the same disease spectrum as adult NPH, likely with overlapping etiology and pathophysiological mechanisms. Exemplary cases consistent with the diagnosis of pediatric NPH selected from the senior author’s neurosurgical practice are then presented alongside the systematic review to aid in discussion of the typical clinical and radiographic manifestations of pediatric NPH. Common co-morbidities and modern surgical treatment options are also described

Laser amygdalohippocampotomy reduces contralateral hippocampal sub-clinical activity in bitemporal epilepsy: A case illustration of responsive neurostimulator ambulatory recordings

Responsive neurostimulation (RNS) is a valuable tool in the diagnosis and treatment of medication refractory epilepsy (MRE) and provides clinicians with better insights into patients’ seizure patterns. In this case illustration, we present a patient with bilateral hippocampal RNS for presumed bilateral mesial temporal lobe epilepsy. The patient subsequently underwent a right sided LITT amygdalohippocampotomy based upon chronic RNS data revealing predominance of seizures from that side. Analyzing electrocorticography (ECOG) from the RNS system, we identified the frequency of high amplitude discharges recorded from the left hippocampal lead pre- and post- right LITT amygdalohippocampotomy. A reduction in contralateral interictal epileptiform activity was observed through RNS recordings over a two-year period, suggesting the potential dependency of the contralateral activity on the primary epileptogenic zone. These findings suggest that early targeted surgical resection or laser ablation by leveraging RNS data can potentially impede the progression of dependent epileptiform activity and may aid in preserving neurocognitive networks. RNS recordings are essential in shaping further management decisions for our patient with a presumed bitemporal epilepsy

Successful Anesthesia Management of Postoperative Maternal Pulmonary Edema and Uterine Hyperactivity following Open Fetal Myelomeningocele Repair

Effective tocolysis is essential after fetal myelomeningocele repair and is associated with the development of pulmonary edema. The increased uterine activity in the immediate postoperative period is commonly treated with magnesium sulfate. However, other tocolytic agents such as nitroglycerine, nifedipine, indomethacin, terbutaline, and atosiban (outside the US) have also been used to combat uterine contractility. The ideal tocolytic regimen which balances the risks and benefits of in-utero surgery has yet to be determined. In this case report, we describe a unique case of fetal myelomeningocele repair complicated by maternal pulmonary edema and increased uterine activity resistant to magnesium sulfate therapy

Hardware failure and reoperation after hybrid anterior cervical corpectomy and discectomy for multilevel spondylotic disease: A retrospective single-institution cohort study

Background context: Hybrid cervical corpectomy/ACDF (HCC-ACDF) is commonly utilized to treat multilevel cervical myelopathy; however, the incidence and mechanisms of hardware failure remain largely uncharacterized. Purpose: We report our experience with this procedure with the goal of describing and better understanding post-operative failures. Methods: The records of 20 consecutive patients who underwent HCC-ACDF for multilevel CSM between June 2015 and December 2018 at this Hospital (blinded) were retrospectively reviewed. All patients were followed for at least 1 year after surgery and were therefore included in the study. Outcome measures include incidence of and reason for subsequent posterior cervical surgery, incidence of and reason for subsequent anterior cervical surgery, progressive symptomatic myelopathy, radiographic hardware failure, and net reduction of pre-operative kyphosis. Continuous variables are reported with means and standard deviations. Fisher’s exact test was used to compare outcomes of binary variables. Results: 20 patients (mean age 60) underwent anterior HCC-ACDF for 3-level CSM. Mean clinical follow up was 26 months (range: 12–56 months). Mean operative time was 205 min and mean blood loss was 105 mL. Radiographic fusion was achieved in 15 of 18 (83%) patients for whom adequate radiographic follow-up was available. HCC-ACDF resulted in an average restoration of 4 degrees of cervical lordosis (standard deviation: 7.3 degrees). One patient (5%) developed symptomatic hardware failure requiring additional surgery. One patient (5%) developed progressive myelopathy within 4 months of surgery. 2 others (10%) developed adjacent segment disease within 2 years of surgery. Three of 20 patients (15%) required subsequent posterior surgery. Conclusions: Rates of hardware failure after HCC-ACDF in our series compare favorably with reports of multilevel anterior corpectomy but are higher than those reported in previous series of HCC-ACDF. No patient characteristics were significantly associated with rates of surgical failure