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Ian F. Dunn, Gavin Dunn and Arthur L. Day

✓ Neurosurgeons in the last half-century have had considerable influence on modern-day athletics. In this article, the authors address the contributions made by neurosurgeons as clinician–scientists, particularly as these relate to the understanding and reduction of the incidence and severity of injury to the nervous system during athletic competition. American football has been a proving ground for the ability of the craniospinal axis to withstand and, in unfortunate cases, succumb to tremendous impact forces; in this way, it has served as a model for translational research and was the arena in which Dr. Richard Schneider made his greatest contributions to sports neurosurgery. Therefore, in his memory and in the spirit of the Schneider lectureship, the authors outline the notable contribution to modern-day athletics made by neurosurgeons as it applies to American football. Neurosurgeons have had considerable influence on reducing injury severity, and this cause has been championed by a few notable individuals whose efforts are discussed herein.

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Wenya Linda Bi, Vikram C. Prabhu and Ian F. Dunn

The epochal developments in the treatment of meningioma—microsurgery, skull base techniques, and radiation therapy—will be appended to include the rational application of targeted and immune therapeutics, previously ill-fitting concepts for a tumor that has traditionally been a regarded as a surgical disease. The genomic and immunological architecture of these tumors continues to be defined in ever-greater detail. Grade I meningiomas are driven by NF2 alterations or mutations in AKT1, SMO, TRAF7, PIK3CA, KLF4, POLR2A, SUFU, and SMARCB1. Higher-grade tumors, however, are driven nearly exclusively by NF2/chr22 loss and are marked by infrequent targetable mutations, although they may harbor a greater mutation burden overall. TERT mutations may be more common in tumors that progress in histological grade; SMARCE1 alteration has become a signature of the clear cell subtype; and BAP1 in rhabdoid variants may confer sensitivity to pharmacological inhibition. Compared with grade I meningiomas, the most prominent alteration in grade II and III meningiomas is a significant increase in chromosomal gains and losses, or copy number alterations, which may have behavioral implications. Furthermore, integrated genomic analyses suggest phenotypic subgrouping by methylation profile and a specific role for PRC2 complex activation. Lastly, there exists a complex phylogenetic relationship among recurrent high-grade tumors, which continues to underscore a role for the most traditional therapy in our arsenal: surgery.

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Saksham Gupta, Wenya Linda Bi and Ian F. Dunn

Surgery is curative for most meningiomas, but a minority of these tumors recur and progress after resection. Initial trials of medical therapies for meningioma utilized nonspecific cytotoxic chemotherapies. The presence of hormone receptors on meningioma ushered in trials of hormone-mimicking agents. While these trials expanded clinical understanding of meningioma, they ultimately had limited efficacy in managing aggressive lesions. Subsequent detection of misregulated proteins and genomic aberrancies motivated the study of therapies targeting specific biological disturbances observed in meningioma. These advances led to trials of targeted kinase inhibitors and immunotherapies, as well as combinations of these agents together with chemotherapies. Prospective trials currently recruiting participants are testing a diverse range of medical therapies for meningioma, and some studies now require the presence of a specific protein alteration or genetic mutation as an inclusion criterion. Increasing understanding of the unique and heterogeneous nature of meningiomas will continue to spur the development of novel medical therapies for the arsenal against aggressive tumors.

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Ian F. Dunn, Mark R. Proctor and Arthur L. Day

✓Lumbar spine injuries in athletes are not uncommon and usually take the form of a mild muscle strain or sprain. More severe injuries sustained by athletes include disc herniations, spondylolistheses, and various types of fracture. The recognition and management of these injuries in athletes involve the additional consideration that to return to play, the lumbar spine must be able to withstand forces similar to those that were injurious. The authors consider common lumbar spine injuries in athletes and discuss management principles for neurosurgeons that are relevant to this population.

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Ian F. Dunn and E. Antonio Chiocca

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Saksham Gupta, Wenya Linda Bi, Alexandra Giantini Larsen, Sally Al-Abdulmohsen, Malak Abedalthagafi and Ian F. Dunn

OBJECTIVE

Craniopharyngiomas are among the most challenging of intracranial tumors to manage because of their pattern of growth, associated morbidities, and high recurrence rate. Complete resection on initial encounter can be curative, but it may be impeded by the risks posed by the involved neurovascular structures. Recurrent craniopharyngiomas, in turn, are frequently refractory to additional surgery and adjuvant radiation or chemotherapy.

METHODS

The authors conducted a review of primary literature.

RESULTS

Recent advances in the understanding of craniopharyngioma biology have illuminated potential oncogenic targets for pharmacotherapy. Specifically, distinct molecular profiles define two histological subtypes of craniopharyngioma: adamantinomatous and papillary. The discovery of overactive B-Raf signaling in the adult papillary subtype has led to reports of targeted inhibitors, with a growing acceptance for refractory cases. An expanding knowledge of the biological underpinnings of craniopharyngioma will continue to drive development of targeted therapies and immunotherapies that are personalized to the molecular signature of each individual tumor.

CONCLUSIONS

The rapid translation of genomic findings to medical therapies for recurrent craniopharyngiomas serves as a roadmap for other challenging neurooncological diseases.

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Chima O. Ohaegbulam, Ian F. Dunn, Pierre d'Hemecourt and Mark R. Proctor

✓ This report describes 3 young male patients with multiple lumbar spondylolyses in combination with a symptomatic epidural hematoma. The records of all 3 patients were reviewed for clinical details. All patients were successfully treated without surgical intervention. Initial neuroimaging results for all patients revealed epidural hematomas, and follow-up imaging confirmed resolution of the hematomas. The relevant literature is briefly reviewed to examine the rarity of this combination. Spontaneous epidural hematomas may occur in the setting of spondylolysis, and this diagnosis should be considered when imaging reveals an unusual epidural lesion in a young active patient.

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Urvashi Upadhyay, Rami O. Almefty, Ian F. Dunn and Ossama Al-Mefty

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Matthew L. Vestal, Emily B. Wong, Dan A. Milner Jr., William B. Gormley and Ian F. Dunn

This report is the first published case of cerebral melioidosis in the western hemisphere. In this paper the authors review the literature on neurological melioidosis and its presentation and treatment in endemic areas, describe the clinical course of this unique case of a presentation of the disease with cranial abscess in the US, review the pathological and radiological findings associated with this seminal case, and put forth recommendations for recognizing and treating possible future instances of the disease within the western hemisphere.

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Rami Almefty, Ian F. Dunn, Svetlana Pravdenkova, Mohammad Abolfotoh and Ossama Al-Mefty

Object

The relentless natural progression of petroclival meningiomas mandates their treatment. The management of these tumors, however, is challenging. Among the issues debated are goals of treatment, outcomes, and quality of life, appropriate extent of surgical removal, the role of skull base approaches, and the efficacy of combined decompressive surgery and radiosurgery. The authors report on the outcome in a series of patients treated with the goal of total removal.

Methods

The authors conducted a retrospective analysis of 64 cases of petroclival meningiomas operated on by the senior author (O.A.) from 1988 to 2012, strictly defined as those originating medial to the fifth cranial nerve on the upper two-thirds of the clivus. The patients' average age was 49 years; the average tumor size (maximum diameter) was 35.48 ± 10.09 mm (with 59 tumors > 20 mm), and cavernous sinus extension was present in 39 patients. The mean duration of follow-up was 71.57 months (range 4–276 months).

Results

In 42 patients, the operative reports allowed the grading of resection. Grade I resection (tumor, dura, and bone) was achieved in 17 patients (40.4%); there was no recurrence in this group (p = 0.0045). Grade II (tumor, dura) was achieved in 15 patients (36%). There was a statistically significant difference in the rate of recurrence with respect to resection grade (Grades I and II vs other grades, p = 0.0052). In all patients, tumor removal was classified based on postoperative contrast-enhanced MRI, and gross-total resection (GTR) was considered to be achieved if there was no enhancement present; on this basis, GTR was achieved in 41 (64%) of 64 patients, with a significantly lower recurrence rate in these patients than in the group with residual enhancement (p = 0.00348). One patient died from pulmonary embolism after discharge.

The mean Karnofsky Performance Status (KPS) score was 85.31 preoperatively (median 90) and improved on follow-up to 88, with 30 patients (47%) having an improved KPS score on follow-up. Three patients suffered a permanent deficit that significantly affected their KPS. Cerebrospinal fluid leak occurred in 8 patients (12.5%), with 2 of them requiring exploration. Eighty-nine percent of the patients had cranial nerve deficits on presentation; of the 54 patients with more than 2 months of follow-up, 21 (32.8%) had persisting cranial nerve deficits. The overall odds of permanent cranial nerve deficit of treated petroclival meningioma was 6.2%. There was no difference with respect to immediate postoperative cranial nerve deficit in patients who had GTR compared with those who had subtotal resection.

Conclusions

Total removal (Grade I or II resection) of petroclival meningiomas is achievable in 76.4% of cases and is facilitated by the use of skull base approaches, with good outcome and functional status. In cases in which circumstances prevent total removal, residual tumors can be followed until progression is evident, at which point further intervention can be planned.