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Eric S. Sussman, Allen L. Ho, Arjun V. Pendharkar and Jamshid Ghajar

Sports-related concussion is a change in brain function following a direct or an indirect force to the head, identified in awake individuals and accounting for a considerable proportion of mild traumatic brain injury. Although the neurological signs and symptoms of concussion can be subtle and transient, there can be persistent sequelae, such as impaired attention and balance, that make affected patients particularly vulnerable to further injury. Currently, there is no accepted definition or diagnostic criteria for concussion, and there is no single assessment that is accepted as capable of identifying all patients with concussion. In this paper, the authors review the available screening tools for concussion, with particular emphasis on the role of visual function testing. In particular, they discuss the oculomotor assessment tools that are being investigated in the setting of concussion screening.

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Jeffrey C. Allen, Jae Ho Kim and Roger J. Packer

✓ A neoadjuvant (preradiotherapy) chemotherapy regimen consisting of either cyclophosphamide alone (60 to 80 mg/kg) or a modified multidrug regimen (vinblastine, bleomycin, cyclophosphamide, and cisplatin) was administered to 15 newly diagnosed patients with histologically confirmed, fully staged, primary germ-cell tumors (GCT's) of the central nervous system (CNS). There were 11 patients with germinomas and four with non-germinoma malignant GCT's. There were six females and nine males, whose median age was 13 years (range 4 months to 24 years). Seven germinoma patients (64%) had disseminated disease. For the germinoma patients, the subsequent radiotherapy dose was modified based on the response to the neoadjuvant chemotherapy, and craniospinal radiotherapy was given only to those with disseminated CNS disease at diagnosis. Ten of the 11 germinoma patients had complete disappearance of all evaluable disease after two courses of chemotherapy (cyclophosphamide in eight and multidrug in three) and one had a partial response. The planned dose of radiotherapy to the primary tumor was reduced from 5500 to 3000 rads, and the craniospinal dose was lowered from 3600 to 2000 rads. Ten patients remain in continuous disease-free remission 20+ to 89+ months after diagnosis (median follow-up period 47 months). All four patients with non-germinoma GCT's received the multidrug regimen, and two of three patients with evaluable disease had a partial response. High-dose regional and craniospinal radiotherapy was administered thereafter, but only two patients remain in their first remission.

Previously untreated germinoma is a highly chemosensitive disease and the neoadjuvant treatment strategy permits the identification of active chemotherapy regimens in newly diagnosed patients. Patients who have complete responses to neoadjuvant chemotherapy tolerate a significant radiotherapy dose reduction without compromising long-term survival, thereby allowing a reduction of some of the late effects of therapeutic radiation. Germinomas tend to disseminate early in the course of the disease and a pre-therapy staging evaluation permits individualized radiotherapy treatment planning.

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Arjun V. Pendharkar, Sabrina L. Levy, Allen L. Ho, Eric S. Sussman, Michelle Y. Cheng and Gary K. Steinberg

Stroke is one of the leading contributors to morbidity, mortality, and health care costs in the United States. Although several preclinical strategies have shown promise in the laboratory, few have succeeded in the clinical setting. Optogenetics represents a promising molecular tool, which enables highly specific circuit-level neuromodulation. Here, the conceptual background and preclinical body of evidence for optogenetics are reviewed, and translational considerations in stroke recovery are discussed.

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Allen L. Ho, Elizabeth Erickson-Direnzo, Arjun V. Pendharkar, Chih-Kwang Sung and Casey H. Halpern

Tremulous voice is a characteristic feature of a multitude of movement disorders, but when it occurs in individuals diagnosed with essential tremor, it is referred to as essential vocal tremor (EVT). For individuals with EVT, their tremulous voice is associated with significant social embarrassment and in severe cases may result in the discontinuation of employment and hobbies. Management of EVT is extremely difficult, and current behavioral and medical interventions for vocal tremor result in suboptimal outcomes. Deep brain stimulation (DBS) has been proposed as a potential therapeutic avenue for EVT, but few studies can be identified that have systematically examined improvements in EVT following DBS. The authors describe a case of awake bilateral DBS targeting the ventral intermediate nucleus for a patient suffering from severe voice and arm tremor. They also present their comprehensive, multidisciplinary methodology for definitive treatment of EVT via DBS. To the authors’ knowledge, this is the first time comprehensive intraoperative voice evaluation has been used to guide microelectrode/stimulator placement, as well as the first time that standard pre- and post-DBS assessments have been conducted, demonstrating the efficacy of this tailored DBS approach.

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Amit Singla, Ning Lin, Allen L. Ho, R. Michael Scott and Edward R. Smith

Surgically created openings such as bur holes can serve as avenues for the development of collateral blood supply to the brain in patients with moyamoya disease. When such collateralization occurs through preexisting shunt catheter sites, the potential exists for perioperative stroke if these vessels are damaged during revision of a ventricular catheter for shunt malfunction. In this paper the authors report on a series of patients with a history of ventriculoperitoneal (VP) shunts who later developed moyamoya disease and were found to have spontaneous transdural collateral vessels at ventricular catheter sites readily visualized on diagnostic angiography. A consecutive surgical series of 412 patients with moyamoya disease treated at Boston Children's Hospital from 1990 to 2010 were reviewed to identify patients with concomitant moyamoya and a VP shunt. The clinical records and angiograms of these patients were reviewed to determine the extent of bur hole collaterals through the shunt site. Three patients were identified who had VP shunts placed for hydrocephalus and subsequently developed moyamoya disease. All 3 patients demonstrated spontaneous transdural collaterals at the ventricular catheter bur hole, as confirmed by angiography during the workup for moyamoya disease. No patients required subsequent revision of their ventricular catheters following the diagnosis of moyamoya. All patients have remained stroke free and clinically stable following pial synangiosis. Although the association of moyamoya and shunted hydrocephalus is rare, it may present a significant potential problem for the neurosurgeon treating a shunt malfunction in this patient population, because shunt bur holes may become entry sites for the ingrowth of significant cortical transdural collateral blood supply to the underlying brain. Shunt revision might therefore be associated with an increased risk of postoperative stroke or operative-site hemorrhage in this population if this vascularization is interrupted when shunt catheters are removed and replaced. A knowledge of the existence of shunt-related collaterals in patients with moyamoya may aid the surgeon in planning shunt revisions and considering, for example, a new entry point for a ventricular catheter, rather than replacing an existing one, to minimize the risk of jeopardizing existing collaterals.

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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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Arjun V. Pendharkar, Eric S. Sussman, Allen L. Ho, Melanie G. Hayden Gephart and Laurence Katznelson

Cushing's disease (CD) is a state of excess glucocorticoid production resulting from an adrenocorticotropic hormone (ACTH)–secreting pituitary adenoma. The gold-standard treatment for CD is transsphenoidal adenomectomy. In the hands of an experienced neurosurgeon, gross-total resection is possible in the majority of ACTH-secreting pituitary adenomas, with early postoperative remission rates ranging from 67% to 95%. In contrast to the strong data in support of resection, the clinical course of postsurgical persistent or recurrent disease remains unclear. There is significant variability in recurrence rates, with reports as high as 36% with a mean time to recurrence of 15–50 months. It is therefore important to develop biochemical criteria that define postsurgical remission and that may provide prognosis for long-term recurrence. Despite the use of a number of biochemical assessments, there is debate regarding the accuracy of these tests in predicting recurrence. Here, the authors review the various biochemical criteria and assess their utility in predicting CD recurrence after resection.

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Allen L. Ho, Yagmur Muftuoglu, Arjun V. Pendharkar, Eric S. Sussman, Brenda E. Porter, Casey H. Halpern and Gerald A. Grant

OBJECTIVE

Stereoelectroencephalography (SEEG) has increased in popularity for localization of epileptogenic zones in drug-resistant epilepsy because safety, accuracy, and efficacy have been well established in both adult and pediatric populations. Development of robot-guidance technology has greatly enhanced the efficiency of this procedure, without sacrificing safety or precision. To date there have been very limited reports of the use of this new technology in children. The authors present their initial experience using the ROSA platform for robot-guided SEEG in a pediatric population.

METHODS

Between February 2016 and October 2017, 20 consecutive patients underwent robot-guided SEEG with the ROSA robotic guidance platform as part of ongoing seizure localization and workup for medically refractory epilepsy of several different etiologies. Medical and surgical history, imaging and trajectory plans, as well as operative records were analyzed retrospectively for surgical accuracy, efficiency, safety, and epilepsy outcomes.

RESULTS

A total of 222 leads were placed in 20 patients, with an average of 11.1 leads per patient. The mean total case time (± SD) was 297.95 (± 52.96) minutes and the mean operating time per lead was 10.98 minutes/lead, with improvements in total (33.36 minutes/lead vs 21.76 minutes/lead) and operative (13.84 minutes/lead vs 7.06 minutes/lead) case times/lead over the course of the study. The mean radial error was 1.75 (± 0.94 mm). Clinically useful data were obtained from SEEG in 95% of cases, and epilepsy surgery was indicated and performed in 95% of patients. In patients who underwent definitive epilepsy surgery with at least a 3-month follow-up, 50% achieved an Engel class I result (seizure freedom). There were no postoperative complications associated with SEEG placement and monitoring.

CONCLUSIONS

In this study, the authors demonstrate that rapid adoption of robot-guided SEEG is possible even at a SEEG-naïve institution, with minimal learning curve. Use of robot guidance for SEEG can lead to significantly decreased operating times while maintaining safety, the overall goals of identification of epileptogenic zones, and improved epilepsy outcomes.

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Allen L. Ho, Austin Y. Feng, Lily H. Kim, Arjun V. Pendharkar, Eric S. Sussman, Casey H. Halpern and Gerald A. Grant

Stereoelectroencephalography (SEEG) is an intracranial diagnostic measure that has grown in popularity in the United States as outcomes data have demonstrated its benefits and safety. The main uses of SEEG include 1) exploration of deep cortical/sulcal structures; 2) bilateral recordings; and 3) 3D mapping of epileptogenic zones. While SEEG has gradually been accepted for treatment in adults, there is less consensus on its utility in children. In this literature review, the authors seek to describe the current state of SEEG with a focus on the more recent technology-enabled surgical techniques and demonstrate its efficacy in the pediatric epilepsy population.

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Allen L. Ho, Anne-Mary N. Salib, Arjun V. Pendharkar, Eric S. Sussman, William J. Giardino and Casey H. Halpern

Alcohol use disorder (AUD) is a difficult to treat condition with a significant global public health and cost burden. The nucleus accumbens (NAc) has been implicated in AUD and identified as an ideal target for deep brain stimulation (DBS). There are promising preclinical animal studies of DBS for alcohol consumption as well as some initial human clinical studies that have shown some promise at reducing alcohol-related cravings and, in some instances, achieving long-term abstinence. In this review, the authors discuss the evidence and concepts supporting the role of the NAc in AUD, summarize the findings from published NAc DBS studies in animal models and humans, and consider the challenges and propose future directions for neuromodulation of the NAc for the treatment of AUD.