Publications

Ansari SF, Eisenberg A, Rodriguez A, Barkhoudarian G, Kelly DF.

Operative Neurosurgery. 2020 Aug 4.

OBJECTIVE
To present a series of patients treated with the SO approach to assess outcomes, the impact of endoscopy, and describe a modified pericranial flap aimed at reducing postoperative frontalis paresis and hypesthesia.

METHODS
A retrospective analysis was undertaken of our prospective database of patients who underwent SO craniotomy for tumor/cyst removal. Patients were evaluated based on pathology, utility of endoscopy, extent of resection, complications, and functional/esthetic recovery.

RESULTS
From 2007 to 2018, 129 operations were performed in 117 patients (54% women; mean age 60 ± 16.5 yr). The most common lesions were meningiomas (43%), gliomas (15%), and metastases (15%). Prior surgery and/or radiation had been performed in 37% and 26% of patients, respectively. Endoscopy was used in 76 (61%) operations and allowed more complete tumor removal in 38 (50%). For first-time operations, gross-total removal was achieved in 78%. Major complications included stroke (3%), cranial nerve deficit (3%), acute hematoma (1%), and cerebrospinal fluid leak (1%). The modified pericranial flap technique used in 18 recent patients resulted in a shorter duration of transient frontalis paresis and forehead hypesthesia with complete functional recovery in all 18.

CONCLUSION
The SO craniotomy is an effective keyhole approach for intra- and extra-axial tumors. Endoscopic assistance may allow additional tumor removal in almost 30% of the cases. The modified pericranial flap appears to accelerate functional recovery, although additional patients and follow-up are required to better assess this technique.

Mallari RJ, Thakur JD, Griffiths C, Krauss H, Eisenberg A, Barkhoudarian G, Kelly, DF.

World Neurosurgery. 2020 Aug 3.

Presentation of tuberculum sella meningioma during pregnancy is uncommon but not rare, accounting for 7% of women in our series. Ideally, surgery is performed in the second trimester, ensuring fetal safety while restoring maternal vision and maintaining pituitary gland function are essential. Depending on tumor size and sellar anatomy, endoscopic endonasal or supraorbital keyhole craniotomy approaches are both viable options.

Christopher Larson, Bryan Oronsky, Sharad Goyal, Carolyn Ray, Farah Hedjran, Terese C. Hammond, Santosh Kesari, Scott Caroen, Michelle Lybeck, Vaughn E. Dobalian, Arnold Oronsky, and Tony Reid

Biochim Biophys Acta Rev Cancer. 2020 Aug 20.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious zoonotic pathogen that has exacted heavy public health, social and economic tolls. In February 2020, the World Health Organization acronymed the disease caused by SARS-CoV-2 as COVID-19, for coronavirus disease 2019. The number of confirmed COVID-19 infections, which has been detected in at least 103 countries, has reached 1,970,225 worldwide as of April 14, 2020 with 124,544 deaths, according to the U.S. Centers for Disease Control and Prevention (CDC).

Many cases of COVID-19 resolve quickly. However, the disease, which, like other respiratory pathogens that cause common cold symptoms is believed to be transmitted through respiratory droplets. Infection with COVID-19 can also lead to significant morbidity and death; this is particularly the case for cancer patients. Moreover, because the signs and symptoms of COVID-19 are easily misattributed to the sequelae of cancer itself, such as pulmonary embolism, or its treatment, such as nausea and diarrhea, diagnosis may be delayed or missed. Potential COVID-19 rule out criteria, based on the Wells' criteria for pulmonary embolism, another protean disease entity, are provided as a decision-making aid. This review summarizes the current understanding of the transmission, clinical presentation, diagnosis and differential diagnosis, pathogenesis, rationale to treat the cancer or not, treatment and prevention of COVID-19 with an emphasis on implications in cancer.

Naveed Wagle, Santosh Kesari

Neuro-Oncology. 2020 Dec 5.

The importance of the blood brain barrier in maintaining homeostatsis on the central nervous system, preventing infection, and selective permeability

Jai Deep Thakur, MD, Regin Jay Mallari, BS, Alex Corlin, BA, Samantha Yawitz, Weichao Huang, MD, Amy Eisenberg, MSN, ARNP, CNRN, Walavan Sivakumar, MD, Howard R. Krauss, MD, Chester Griffiths, MD, Garni Barkhoudarian, MD, and Daniel F. Kelly, MD

Neurological Focus. 2020 Oct 1.

OBJECTIVE
Increased lifespan has led to more elderly patients being diagnosed with meningiomas. In this study, the authors sought to analyze and compare patients ≥ 65 years old with those < 65 years old who underwent minimally invasive surgery for meningioma. To address surgical selection criteria, the authors also assessed a cohort of patients managed without surgery.

METHODS
In a retrospective analysis, consecutive patients with meningiomas who underwent minimally invasive (endonasal, supraorbital, minipterional, transfalcine, or retromastoid) and conventional surgical treatment approaches during the period from 2008 to 2019 were dichotomized into those ≥ 65 and those < 65 years old to compare resection rates, endoscopy use, complications, and length of hospital stay (LOS). A comparator meningioma cohort of patients ≥ 65 years old who were observed without surgery during the period from 2015 to 2019 was also analyzed.

RESULTS
Of 291 patients (median age 60 years, 71.5% females, mean follow-up 36 months) undergoing meningioma resection, 118 (40.5%) were aged ≥ 65 years and underwent 126 surgeries, including 20% redo operations, as follows: age 65–69 years, 46 operations; 70–74 years, 40 operations; 75–79 years, 17 operations; and ≥ 80 years, 23 operations. During 2015–2019, of 98 patients referred for meningioma, 67 (68%) had surgery, 1 (1%) had radiosurgery, and 31 (32%) were observed. In the 11-year surgical cohort, comparing 173 patients < 65 years versus 118 patients ≥ 65 years old, there were no significant differences in tumor location, size, or outcomes. Of 126 cases of surgery in 118 elderly patients, the approach was a minimally invasive approach to skull base meningioma (SBM) in 64 cases (51%) as follows: endonasal 18, supraorbital 28, minipterional 6, and retrosigmoid 12. Endoscope-assisted surgery was performed in 59.5% of patients. A conventional approach to SBM was performed in 15 cases (12%) (endoscope-assisted 13.3%), and convexity craniotomy for non–skull base meningioma (NSBM) in 47 cases (37%) (endoscope-assisted 17%). In these three cohorts (minimally invasive SBM, conventional SBM, and NSBM), the gross-total/near-total resection rates were 59.5%, 60%, and 91.5%, respectively, and an improved or stable Karnofsky Performance Status score occurred in 88.6%, 86.7%, and 87.2% of cases, respectively. For these 118 elderly patients, the median LOS was 3 days, and major complications occurred in 10 patients (8%) as follows: stroke 4%, vision decline 3%, systemic complications 0.7%, and wound infection or death 0. Eighty-three percent of patients were discharged home, and readmissions occurred in 5 patients (4%). Meningioma recurrence occurred in 4 patients (3%) and progression in 11 (9%). Multivariate regression analysis showed no significance of American Society of Anesthesiologists physical status score, comorbidities, or age subgroups on outcomes; patients aged ≥ 80 years showed a trend of longer hospitalization.

CONCLUSIONS
This analysis suggests that elderly patients with meningiomas, when carefully selected, generally have excellent surgical outcomes and tumor control. When applied appropriately, use of minimally invasive approaches and endoscopy may be helpful in achieving maximal safe resection, reducing complications, and promoting short hospitalizations. Notably, one-third of our elderly meningioma patients referred for possible surgery from 2015 to 2019 were managed nonoperatively.

Keywords: meningioma; elderly; intracranial; tumor; endoscopic; keyhole
ABBREVIATIONS ASA = American Society of Anesthesiologists; EBL = estimated blood loss; GTR = gross-total resection; KPS = Karnofsky Performance Status; LOS = length of hospital stay; NTR = near-total resection; SRS = stereotactic radiosurgery; STR = subtotal resection.
Intracranial meningiomas are the most common primary brain tumor, and in most adult surgical series, almost half of meningioma patients are ≥ 65 years old.1 Secondary to improved life

Jose Carrillo, Santosh Kesari
Translational Cancer Research. 2018 Oct 24.

Stuart H. Isaacson, MD,1 Elizabeth Peckham, DO,2 Winona Tse, MD,3 Olga Waln, MD,4 Christopher Way, DO,5 Melita T. Petrossian, MD,6 Nabila Dahodwala, MD, MSc,7 Michael J. Soileau, MD,8 Mark Lew, MD,9 Cameron Dietiker, MD,10 Nijee Luthra, MD,10 Pinky Agarwal, MD, FAAN,11 Rohit Dhall, MD, MSPH,12 John Morgan, MD, PhD,13 Nicole Calakos, MD, PhD,14 Theresa A. Zesiewicz, MD,15 Ejaz A. Shamim, MD, MS, MBA, FAAN,16 Rajeev Kumar, MD,17 Peter LeWitt, MD,18 Holly A. Shill, MD, FAAN,19 Adam Simmons, MD,20 Fernando L. Pagan, MD,21 Pravin Khemani, MD,22 Jessica Tate, MD,23 Brian Maddux, MD,24 Lan Luo, MD, MS,25 William Ondo, MD,4 Mark Hallett, MD,26 Apoorva Rajagopal, PhD,27 Paula Chidester, MS,27 Kathryn H. Rosenbluth, PhD,27 Scott L. Delp, PhD,28 and Rajesh Pahwa, MD29

Tremor Other Hyperkinet Mov (N Y). 2020 Aug 14.

Highlights
This prospective study is one of the largest clinical trials in essential tremor to date. Study findings suggest that individualized non-invasive neuromodulation therapy used repeatedly at home over three months results in safe and effective hand tremor reduction and improves quality of life for many essential tremor patients.

Background:
Two previous randomized, controlled, single-session trials demonstrated efficacy of non-invasive neuromodulation therapy targeting the median and radial nerves for reducing hand tremor. This current study evaluated efficacy and safety of the therapy over three months of repeated home use.

Methods:
This was a prospective, open-label, post-clearance, single-arm study with 263 patients enrolled across 26 sites. Patients were instructed to use the therapy twice daily for three months. Pre-specified co-primary endpoints were improvements on clinician-rated Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS) and patient-rated Bain & Findley Activities of Daily Living (BF-ADL) dominant hand scores. Other endpoints included improvement in the tremor power detected by an accelerometer on the therapeutic device, Clinical and Patient Global Impression scores (CGI-I, PGI-I), and Quality of Life in Essential Tremor (QUEST) survey.

Results:
205 patients completed the study. The co-primary endpoints were met (p≪0.0001), with 62% (TETRAS) and 68% (BF-ADL) of ‘severe’ or ‘moderate’ patients improving to ‘mild’ or ‘slight’. Clinicians (CGI-I) reported improvement in 68% of patients, 60% (PGI-I) of patients reported improvement, and QUEST improved (p = 0.0019). Wrist-worn accelerometer recordings before and after 21,806 therapy sessions showed that 92% of patients improved, and 54% of patients experienced ≥50% improvement in tremor power. Device-related adverse events (e.g., wrist discomfort, skin irritation, pain) occurred in 18% of patients. No device-related serious adverse events were reported.

Discussion:
This study suggests that non-invasive neuromodulation therapy used repeatedly at home over three months results in safe and effective hand tremor reduction in many essential tremor patients.

Barkhoudarian G, Palejwala SK, Ansari S, Eisenberg AA, Huang X, Griffiths CF, Cohan P, Rettinger S, Lavin N, Kelly DF. Pituitary. 2019 Aug;22(4):372. doi: 10.1007/s11102-019-00975-7

Villanueva P, Louis RG, Cutler AR, Wei H, Sale D, Duong HT, Barkhoudarian G, Kelly DF. Oper Neurosurg (Hagerstown). 2015 Dec 1;11(4):475-483. doi: 10.1227/NEU.0000000000000970. PMID: 29506159

Orozco JIJ, Knijnenburg TA, Manughian-Peter AO, Salomon MP, Barkhoudarian G, Jalas JR, Wilmott JS, Hothi P, Wang X, Takasumi Y, Buckland ME, Thompson JF, Long GV, Cobbs CS, Shmulevich I, Kelly DF, Scolyer RA, Hoon DSB, Marzese DM. Nat Commun. 2018 Nov 6;9(1):4627. doi: 10.1038/s41467-018-06715-y. PMID: 30401823