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Mohan R. Sharma, David W. Newell and Gerald A. Grant

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Ben Waldau, Gerald Grant and Herbert Fuchs

✓The authors present the case of a child with an untreated lipomyelomeningocele who developed an acquired Chiari malformation Type I (CM-I) with a large syrinx over the course of 3 years. To the best of the authors' knowledge, this is the first report to document a case in which an acquired CM-I evolved in a patient with an untreated tethered cord.

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Gerald A. Grant, Donald Farrell and Daniel L. Silbergeld

✓ The neurosurgical management of intrinsic brain tumors and brain metastases mandates maximum resection with preservation of functional cortex. There have been previous reports on the use of cortical somatosensory evoked potentials (SSEPs) for localization of functional cortex prior to resection. The identification of rolandic cortex with the use of intraoperative SSEP monitoring enables the neurosurgeon to tailor the surgery to achieve a greater extent of resection while minimizing the risk of morbidity. The use of continuous SSEP monitoring during resection to provide an ongoing functional assessment of somatosensory cortex has not been reported. This powerful technique is illustrated using four case examples.

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Anthony M. Avellino, Gerald A. Grant, A. Basil Harris, Sharon K. Wallace and Cheng-Mei Shaw

✓ In the central nervous system, recurrence of intracranial Masson's vegetant intravascular hemangioendothelioma (MVIH) is rare. To the authors' knowledge, only three recurrent intracranial cases have been reported.

The authors report the case of a 75-year-old woman with a recurrent left-sided cerebellopontine angle and middle cranial fossa MVIH. When the patient was 62 years of age, she underwent preoperative embolization and subtotal resection of the intracranial lesion followed by postoperative radiotherapy. She was well and free from disease until 9 years postoperatively when she became symptomatic. At 71 years of age, the patient again underwent preoperative embolization and near-gross-total resection of the lesion. Follow-up imaging performed 15 months later revealed tumor recurrence, and she underwent stereotactic gamma knife radiosurgery. At a 2.75-year follow-up review, the patient's imaging studies revealed stable residual tumor.

This case report is unique in that it documents the clinical and pathological features, surgical and postoperative treatment, and long-term follow-up review of a patient with recurrent intracranial MVIH and suggests that this unusual vascular lesion is a slow-growing benign tumor rather than a reactive process. Because the pathological composition of the lesion may resemble an angiosarcoma, understanding this benign vascular neoplasm is crucial so that an erroneous diagnosis of malignancy is not made and unnecessary adjuvant therapy is not given.

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Tej D. Azad, James Pan, Ian D. Connolly, Austin Remington, Christy M. Wilson and Gerald A. Grant

Resection of brain tumors is followed by chemotherapy and radiation to ablate remaining malignant cell populations. Targeting these populations stands to reduce tumor recurrence and offer the promise of more complete therapy. Thus, improving access to the tumor, while leaving normal brain tissue unscathed, is a critical pursuit. A central challenge in this endeavor lies in the limited delivery of therapeutics to the tumor itself. The blood-brain barrier (BBB) is responsible for much of this difficulty but also provides an essential separation from systemic circulation. Due to the BBB's physical and chemical constraints, many current therapies, from cytotoxic drugs to antibody-based proteins, cannot gain access to the tumor. This review describes the characteristics of the BBB and associated changes wrought by the presence of a tumor. Current strategies for enhancing the delivery of therapies across the BBB to the tumor will be discussed, with a distinction made between strategies that seek to disrupt the BBB and those that aim to circumvent it.

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James Pan, Ian D. Connolly, Sean Dangelmajer, James Kintzing, Allen L. Ho and Gerald Grant

Brain injuries are becoming increasingly common in athletes and represent an important diagnostic challenge. Early detection and management of brain injuries in sports are of utmost importance in preventing chronic neurological and psychiatric decline. These types of injuries incurred during sports are referred to as mild traumatic brain injuries, which represent a heterogeneous spectrum of disease. The most dramatic manifestation of chronic mild traumatic brain injuries is termed chronic traumatic encephalopathy, which is associated with profound neuropsychiatric deficits. Because chronic traumatic encephalopathy can only be diagnosed by postmortem examination, new diagnostic methodologies are needed for early detection and amelioration of disease burden. This review examines the pathology driving changes in athletes participating in high-impact sports and how this understanding can lead to innovations in neuroimaging and biomarker discovery.

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Morgan Bliss, Gerald Grant, Ethan Tittler, Tina Loven, Kristen W. Yeom and Douglas Sidell

In contrast to more common nasal and cervical lesions, the frontotemporal pit is a rarely encountered lesion that is often associated with a dermoid and may track intracranially. Due to delays in diagnosis, the propensity to spread intracranially, and the risk of infection, awareness of these lesions and appropriate diagnosis and management are important. The authors present 2 cases of frontotemporal pits from a single institution. Epidemiology, presentation, and management recommendations are discussed.

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Srinivasan Mukundan, Herbert Fuchs, Michael J. Alexander and Gerald A. Grant

✓The authors report the first clinical use of 3-tesla dynamic contrast-enhanced magnetic resonance (MR) angiography for the diagnosis of a vascular malformation in a pediatric patient. The supply and drainage of an arteriovenous malformation were accurately demonstrated on MR angiography, which was performed without sedating the patient. This lesion was confirmed on catheter angiography, and definitive treatment via embolization was undertaken in a single session. The patient's therapeutic response will be followed with surveillance dynamic MR imaging.

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Terry C. Burns, Ahmed J. Awad, Matthew D. Li and Gerald A. Grant

Brain radiation is a fundamental tool in neurooncology to improve local tumor control, but it leads to profound and progressive impairments in cognitive function. Increased attention to quality of life in neurooncology has accelerated efforts to understand and ameliorate radiation-induced cognitive sequelae. Such progress has coincided with a new understanding of the role of CNS progenitor cell populations in normal cognition and in their potential utility for the treatment of neurological diseases. The irradiated brain exhibits a host of biochemical and cellular derangements, including loss of endogenous neurogenesis, demyelination, and ablation of endogenous oligodendrocyte progenitor cells. These changes, in combination with a state of chronic neuroinflammation, underlie impairments in memory, attention, executive function, and acquisition of motor and language skills. Animal models of radiation-induced brain injury have demonstrated a robust capacity of both neural stem cells and oligodendrocyte progenitor cells to restore cognitive function after brain irradiation, likely through a combination of cell replacement and trophic effects. Oligodendrocyte progenitor cells exhibit a remarkable capacity to migrate, integrate, and functionally remyelinate damaged white matter tracts in a variety of preclinical models. The authors here critically address the opportunities and challenges in translating regenerative cell therapies from rodents to humans. Although valiant attempts to translate neuroprotective therapies in recent decades have almost uniformly failed, the authors make the case that harnessing human radiation-induced brain injury as a scientific tool represents a unique opportunity to both successfully translate a neuroregenerative therapy and to acquire tools to facilitate future restorative therapies for human traumatic and degenerative diseases of the central nervous system.

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Kunal Varshneya, Adrian J. Rodrigues, Zachary A. Medress, Martin N. Stienen, Gerald A. Grant, John K. Ratliff and Anand Veeravagu

OBJECTIVE

Skull fractures are common after blunt pediatric head trauma. CSF leaks are a rare but serious complication of skull fractures; however, little evidence exists on the risk of developing a CSF leak following skull fracture in the pediatric population. In this epidemiological study, the authors investigated the risk factors of CSF leaks and their impact on pediatric skull fracture outcomes.

METHODS

The authors queried the MarketScan database (2007–2015), identifying pediatric patients (age < 18 years) with a diagnosis of skull fracture and CSF leak. Skull fractures were disaggregated by location (base, vault, facial) and severity (open, closed, multiple, concomitant cerebral or vascular injury). Descriptive statistics and hypothesis testing were used to compare baseline characteristics, complications, quality metrics, and costs.

RESULTS

The authors identified 13,861 pediatric patients admitted with a skull fracture, of whom 1.46% (n = 202) developed a CSF leak. Among patients with a skull fracture and a CSF leak, 118 (58.4%) presented with otorrhea and 84 (41.6%) presented with rhinorrhea. Patients who developed CSF leaks were older (10.4 years vs 8.7 years, p < 0.0001) and more commonly had skull base (n = 183) and multiple (n = 22) skull fractures (p < 0.05). These patients also more frequently underwent a neurosurgical intervention (24.8% vs 9.6%, p < 0.0001). Compared with the non–CSF leak population, patients with a CSF leak had longer average hospitalizations (9.6 days vs 3.7 days, p < 0.0001) and higher rates of neurological deficits (5.0% vs 0.7%, p < 0.0001; OR 7.0; 95% CI 3.6–13.6), meningitis (5.5% vs 0.3%, p < 0.0001; OR 22.4; 95% CI 11.2–44.9), nonroutine discharge (6.9% vs 2.5%, p < 0.0001; OR 2.9; 95% CI 1.7–5.0), and readmission (24.7% vs 8.5%, p < 0.0001; OR 3.4; 95% CI 2.5–4.7). Total costs at 90 days for patients with a CSF leak averaged $81,206, compared with $32,831 for patients without a CSF leak (p < 0.0001).

CONCLUSIONS

The authors found that CSF leaks occurred in 1.46% of pediatric patients with skull fractures and that skull fractures were associated with significantly increased rates of neurosurgical intervention and risks of meningitis, hospital readmission, and neurological deficits at 90 days. Pediatric patients with skull fractures also experienced longer average hospitalizations and greater healthcare costs at presentation and at 90 days.