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

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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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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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Kai J. Miller, Casey H. Halpern, Mark F. Sedrak, John A. Duncan III and Gerald A. Grant

OBJECTIVE

Stereotactic laser ablation and neurostimulator placement represent an evolution in staged surgical intervention for epilepsy. As this practice evolves, optimal targeting will require standardized outcome measures that compare electrode lead or laser source with postprocedural changes in seizure frequency. The authors propose and present a novel stereotactic coordinate system based on mesial temporal anatomical landmarks to facilitate the planning and delineation of outcomes based on extent of ablation or region of stimulation within mesial temporal structures.

METHODS

The body of the hippocampus contains a natural axis, approximated by the interface of cornu ammonis area 4 and the dentate gyrus. The uncal recess of the lateral ventricle acts as a landmark to characterize the anterior-posterior extent of this axis. Several volumetric rotations are quantified for alignment with the mesial temporal coordinate system. First, the brain volume is rotated to align with standard anterior commissure–posterior commissure (AC-PC) space. Then, it is rotated through the axial and sagittal angles that the hippocampal axis makes with the AC-PC line.

RESULTS

Using this coordinate system, customized MATLAB software was developed to allow for intuitive standardization of targeting and interpretation. The angle between the AC-PC line and the hippocampal axis was found to be approximately 20°–30° when viewed sagittally and approximately 5°–10° when viewed axially. Implanted electrodes can then be identified from CT in this space, and laser tip position and burn geometry can be calculated based on the intraoperative and postoperative MRI.

CONCLUSIONS

With the advent of stereotactic surgery for mesial temporal targets, a mesial temporal stereotactic system is introduced that may facilitate operative planning, improve surgical outcomes, and standardize outcome assessment.

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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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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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Shahid M. Nimjee, Ciaran J. Powers, Roger E. McLendon, Gerald A. Grant and Herbert E. Fuchs

Cerebrospinal fluid overproduction resulting in communicating hydrocephalus is observed in patients who have choroid plexus papilloma or choroid plexus carcinoma. Less often, patients with these conditions have diffuse villous hyperplasia. Prior studies report CSF production greater than 3 L per day in these patients. These patients are treated with CSF shunting or by either unilateral choroid plexectomy or staged bilateral choroid plexectomy. The authors present a patient who had a number of congenital anomalies and a karyotype that revealed balanced translocations, 5 to 7 and 9 to 11. She presented with hydrocephalus and had CSF production of 5 L per day, greater output than ever previously reported. She was treated with a single-stage bilateral choroid plexectomy. Histopathological analysis revealed a bilateral choroid plexus papilloma. Postoperatively, the patient responded well clinically and showed radiographic improvement of her hydrocephalus. Bilateral choroid plexus papilloma has been reported in the literature as a cause for neonatal and congenital hydrocephalus. It can result in high CSF output and can be successfully treated with a single-stage bilateral choroid plexectomy. Further studies are ongoing to identify genes involved in embryogenesis of the choroid plexus.

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Shahid M. Nimjee, Tony P. Smith, Ronald J. Kanter, Warwick Ames, Kelly A. Machovec, Gerald A. Grant and Ali R. Zomorodi

Large cerebral aneurysms of the basilar apex are difficult to treat. Recently, endovascular treatment has mitigated much of the morbidity associated with treating these lesions. However, the morphology of aneurysms of the vertebrobasilar system can preclude endovascular treatment. Rapid ventricular pacing (RVP) facilitates open surgical treatment of cerebral aneurysms. It can assist in reducing the pressure of the neck of the aneurysm, allowing safe application of a clip. The authors present a case of a pediatric patient who developed a basilar artery pseudoaneurysm that required surgery. Given the large size of the aneurysm, RVP was performed, allowing the surgeons to dissect the dome of the aneurysm from the surrounding tissue and pontine perforating branches away from the lesion to safely clip the lesion. The patient had an uneventful recovery. To the authors' knowledge, this represents the first known case of RVP to aid in basilar artery clip occlusion in a pediatric patient.

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Gerald A. Grant, Joseph R. Meno, Thien-Son Nguyen, Kathe A. Stanness, Damir Janigro and H. Richard Winn

Object. Excitatory amino acid (EAA) uptake by neurons and glia acts synergistically with stereoselective transport across the blood—brain barrier (BBB) to maintain EAA homeostasis in the brain. The endogenous neuroprotectant adenosine counteracts many aspects of excitotoxicity by increasing cerebral blood flow and by producing pre- and postsynaptic actions on neurons. In the present study, the authors explored the effect of adenosine on EAA transport across the BBB.

Methods. The effects of adenosine on the permeability of the BBB and transport of aspartate and glutamate across the BBB were studied in a well-characterized isolated penetrating cerebral arteriole preparation suitable for simultaneous investigations of changes in diameter and permeability. At concentrations within the physiological to low pathophysiological range (10−7–10−6 M), the net vectorial transport of [3H]l-glutamate or [3H]l-aspartate from blood to brain was significantly attenuated, whereas there was no effect of adenosine on paracellular BBB permeability to [14C]sucrose or [3H]d-aspartate. With higher concentrations of adenosine (10−4 M and 10−3 M) the net vectorial transport of [3H]l-glutamate and [3H]l-aspartate returned toward baseline. At 10−3 M, the permeability to [14C]sucrose was significantly altered, indicating a breakdown in the BBB. The effect of adenosine (10−6 M) was blocked by theophylline, a blocker of the A1 and A2 receptors of adenosine.

Conclusions. Adenosine-mediated modulation of glutamate and aspartate transport across the BBB is a novel physiological finding.