Ariane Lewis, Amol Raheja, and Ian E. McCutcheon
Amol Raheja, Howard Colman, Cheryl A. Palmer, and William T. Couldwell
Sunitinib is a multiple tyrosine kinase inhibitor with antiangiogenic, cytostatic, and antimigratory activity for meningiomas. A recent clinical trial of sunitinib for treatment of recurrent Grade II and III meningiomas suggested potential efficacy in this population, but only 2 patients exhibited significant radiographic response with tumor volume reduction. The authors illustrate another such case and discuss a complication related to this dramatic tumor volume reduction in aggressive skull base meningiomas.
The authors describe the case of a 39-year-old woman who had undergone repeat surgical interventions and courses of radiotherapy over the previous 11 years for recurrent cranial and spinal meningiomas. Despite 4 operations over the course of 4 years on her right petroclival meningioma with cavernous sinus and jugular fossa extensions, she had progressive neurological deficits and tumor recurrences. The specimen histology progressed from WHO Grade I initially to Grade II at the time of the third recurrence. The lesion was then irradiated 3 times using stereotactic radiosurgery for further recurrences. More recently, the tumor size increased rapidly on imaging, in association with progressive neurological symptoms arising from brainstem compression and vasogenic edema. Institution of sunitinib therapy yielded a dramatic radiographic response, with marked reduction in the tumor volume and reduction of brainstem vasogenic edema within a few weeks of initiation of treatment. The significant radiographic response of tumor in the clival region was also associated with CSF rhinorrhea from a dural breach created by resolution of the invasive skull base meningioma, which necessitated withholding the sunitinib medication. To address the leak, the authors undertook surgical exploration and transsphenoidal packing using an autologous fat graft and a vascularized pedicled nasoseptal flap. The patient has done well during follow-up of 3 months after packing, with no evidence of recurrent CSF leak, and the medication was subsequently restarted.
Prior clinical data and the dramatic radiographic response in this patient suggest that sunitinib holds promising therapeutic potential in carefully selected patients with recurrent atypical meningiomas where conventional strategies have been exhausted. There is a potential risk of associated CSF rhinorrhea, especially in more invasive skull base lesions showing dramatic radiographic response.
Gmaan Alzhrani, Yair M. Gozal, Ilyas Eli, Walavan Sivakumar, Amol Raheja, Douglas L. Brockmeyer, and William T. Couldwell
Surgical treatment of pathological processes involving the ventral craniocervical junction (CCJ) traditionally involves anterior and posterolateral skull base approaches. In cases of bilateral extension, when lesions extend beyond the midline to the contralateral side, a unilateral corridor may result in suboptimal resection. In these cases, the lateral extent of the tumor will prevent extirpation of the lesion via anterior surgical approaches. The authors describe a unilateral operative corridor developed along an extreme lateral trajectory to the anterior aspect of the clival and upper cervical dura, allowing exposure and resection of tumor on the contralateral side. This approach is used when the disease involves the bone structures inherent to stability at the anterior CCJ.
To achieve exposure of the ventral CCJ, an extreme lateral transcondylar transodontoid (ELTO) approach was performed with transposition of the ipsilateral vertebral artery, followed by drilling of the C1 anterior arch. Resection of the odontoid process allowed access to the contralateral component of lesions across the midline to the region of the extracranial contralateral vertebral artery, maximizing resection.
Exposure and details of the surgical procedure were derived from anatomical cadavers. At the completion of cadaveric dissection, morphometric measurements of the relevant anatomical landmarks were obtained. Illustrative case examples for approaching ventral CCJ chordomas via the ELTO approach are presented.
The ELTO approach provides a safe and direct surgical corridor to treat complex lesions at the ventral CCJ with bilateral extension through a single operative corridor. This approach can be combined with other lateral approaches or posterior infratemporal approaches to remove more extensive lesions involving the rostral clivus, jugular foramen, and temporal bone.
Amol Raheja, Shashwat Mishra, Kanwaljeet Garg, Varidh Katiyar, Ravi Sharma, Vivek Tandon, Revanth Goda, Ashish Suri, and Shashank S. Kale
Extracorporeal telescopes (exoscopes) have been the latest addition to the neurosurgeons’ armamentarium, acting as a bridge between operating microscopes and endoscopes. However, to the authors’ knowledge there are no published preclinical laboratory studies of the accuracy, efficiency, and dexterity of neurosurgical training for the use of 2D or 3D exoscopes compared with microscopes.
In a controlled experimental setup, 22 participating neurosurgery residents performed simple (2D) and complex (3D) motor tasks with three visualization tools in alternating sequence: a 2D exoscope, 3D exoscope, and microscope, using a block randomization model based on the neurosurgeons’ prior training experience (novice, intermediate, and senior: n = 6, 12, and 4, respectively). Performance scores (PS; including error and efficiency scores) and dexterity scores (DS) were calculated to objectify the accuracy, efficiency, and finesse of task performance. Repeated measures ANOVA analysis was used to compare the PS, DS, and cumulative scores (CS) of candidates using the three visualization aids. Bland-Altman plots and intraclass correlation coefficients were generated to quantify intraobserver and interobserver agreement for DS. Subgroup analysis was performed to assess the impact of participants’ prior training. A postexercise survey was conducted to assess the comfort level (on a 10-point analog scale) of the participants while using each visualization tool for performing the suturing task.
PS, DS, and CS were significantly impacted by the visualization tool utilized for 2D motor tasks (p < 0.001 for each), with the microscope faring better than the 2D exoscope (p = 0.04) or 3D exoscope (p = 0.008). The PS for the 3D object transfer task was significantly influenced by the visualization aid used (p = 0.007), with the microscope and 3D exoscope faring better than the 2D exoscope (p = 0.04 for both). The visualization instrument used significantly affected the DS and CS for the suturing task (p < 0.001 for both), with the microscope again scoring better than the 2D exoscope (p < 0.001) or 3D exoscope (p = 0.005). The impact of the visualization aid was more apparent in participants with a shorter duration of residency (novice, p = 0.03; intermediate, p = 0.0004). Participants also felt the greatest operational comfort while working with a microscope, 3D exoscope, and 2D exoscope, in that order (p < 0.0001).
Compared with 3D and 2D exoscopes, an operating microscope provides better dexterity and performance and a greater operational comfort level for neurosurgeons while they are performing 2D or 3D motor tasks. For performing complex 3D motor tasks, 3D exoscopes offer selective advantages in dexterity, performance, and operational comfort level over 2D exoscopes. The relative impact of visualization aids on surgical proficiency gradually weakens as the participants’ residency duration increases.
Amol Raheja, Aleksandra Sowder, Cheryl Palmer, Fausto J. Rodriguez, and William T. Couldwell
Epstein-Barr virus (EBV)–associated smooth muscle tumors (SMTs) have recently been associated with primary and secondary immunodeficiencies. They are broadly divided into 3 subgroups: HIV-related, posttransplant, and congenital immunodeficiency. Subsequent to organ transplantation and acquired immunosuppression, a few cases of EBV-associated SMTs have been described in the liver, respiratory tract, and gastrointestinal system. To the authors' knowledge, intracranial involvement after peripheral blood stem cell transplantation has never been reported previously. The authors describe the case of a 65-year-old woman who presented with recent-onset painful ophthalmoplegia. She had a prior history of acute myelogenous leukemia requiring allogenic peripheral blood stem cell transplantation 2 years earlier, but she was in a remission phase. Imaging revealed a T1/T2 isointense, homogeneously enhancing lesion of the left cavernous sinus. A presumptive diagnosis of Tolosa-Hunt syndrome was made, and she was treated with steroids; however, her symptoms progressed quickly and repeat imaging revealed that the lesion was growing. To rule out leukemic deposits, a minimally invasive lateral orbitotomy extradural transcavernous approach was performed for biopsy sampling and debulking of the lesion. The biopsied tumor tissue was found to be infiltrative, grayish, firm, and moderately vascular. The final pathology results indicated an EBV-associated SMT of the cavernous sinus. Subsequently, the patient's steroid treatment was stopped and she had obtained partial symptomatic relief at her last follow-up visit, 3 months after surgery. EBV-associated SMT should be included in the differential diagnosis for intracranial and dural-based central nervous system lesions, especially in immunocompromised patients. Paradoxical response to steroids with worsening of symptoms is a hallmark of EBV-associated SMTs.
Chinmaya Dash, Tejas Venkataram, Nishant Goyal, Jitender Chaturvedi, Amol Raheja, Raghav Singla, Jayesh Sardhara, and Ravi Gupta
The COVID-19 pandemic has forced medical professionals throughout the world to adapt to the changing medical scenario. The objective of this survey was to assess the change in neurosurgical training in India following the COVID-19 pandemic.
Between May 7, 2020, and May 16, 2020, a validated questionnaire was circulated among neurosurgical residents across India by social media, regarding changes in the department’s functioning, patient interaction, surgical exposure, changes in academics, and fears and apprehensions associated with the pandemic. The responses were kept anonymous and were analyzed for changes during the COVID-19 pandemic compared to before the pandemic.
A total of 118 residents from 29 neurosurgical training programs across 17 states/union territories of the country gave their responses to the survey questionnaire. The survey revealed that the surgical exposure of neurosurgical residents has drastically reduced since the onset of the COVID-19 pandemic, from an average of 39.86 surgeries performed/assisted per month (median 30) to 12.31 per month (median 10), representing a decrease of 67.50%. The number of academic sessions has fallen from a median of 5 per week to 2 per week. The survey uncovered the lack of universal guidelines and homogeneity regarding preoperative COVID-19 testing. The survey also reveals reluctance toward detailed patient examinations since the COVID-19 outbreak. The majority of respondents felt that the COVID-19 pandemic will hamper their operative and clinical skills. Fear of rescheduling or deferring of licensing examinations was significantly higher among those closest to the examination (p = 0.002).
The adverse impact of the pandemic on neurosurgical training needs to be addressed. While ensuring the safety of the residents, institutes and neurosurgical societies/bodies must take it upon themselves to ensure that their residents continue to learn and develop neurosurgical skills during these difficult times.
Amol Raheja, Nitish Agarwal, Sarita Mohapatra, Vivek Tandon, Sachin Anil Borkar, P. Sarat Chandra, Shashank S. Kale, and Ashish Suri
The COVID-19 pandemic has severely impacted healthcare systems globally. The need of the hour is the development of effective strategies for protecting the lives of healthcare providers (HCPs) and judicious triage for optimal utilization of human and hospital resources. During this pandemic, neurosurgery, like other specialties, must transform, innovate, and adopt new guidelines and safety protocols for reducing the risk of cross-infection of HCPs without compromising patient care. In this article, the authors discuss the current neurosurgical practice guidelines at a high-volume tertiary care referral hospital in India and compare them with international guidelines and global consensus for neurosurgery practice in the COVID-19 era. Additionally, the authors highlight some of the modifications incorporated into their clinical practice, including those for stratification of neurosurgical cases, patient triaging based on COVID-19 testing, optimal manpower management, infrastructure reorganization, evolving modules for resident training, and innovations in operating guidelines. The authors recommend the use of their blueprint for stratification of neurosurgical cases, including their protocol for algorithmic patient triage and management and their template for manpower allocation to COVID-19 duty, as a replicable model for efficient healthcare delivery.
Vijay M. Ravindra, Amol Raheja, Heather Corn, Meghan Driscoll, Corrine Welt, Debra L. Simmons, and William T. Couldwell
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma and comprises approximately 30% of all lymphomas. Patients typically present with a nonpainful mass in the neck, groin, or abdomen associated with constitutional symptoms. In this report, however, the authors describe a rare case of a 61-year-old woman with hyperprolactinemia, hypothyroidism, and acromegaly (elevation of insulin-like growth factor-1 [IGF-1]) with elevated growth hormone–releasing hormone (GHRH) in whom an MRI demonstrated diffuse enlargement of the pituitary gland. Despite medical treatment, the patient had persistent elevation of IGF-1. She underwent a transsphenoidal biopsy, which yielded a diagnosis of DLBCL with an activated B-cell immunophenotype with somatotroph hyperplasia. After stereo-tactic radiation therapy in combination with chemotherapy, she is currently in remission from her lymphoma and has normalized IGF-1 levels without medical therapy, 8 months after her histopathological diagnosis. This is the only reported case of its kind and displays the importance of a broad differential diagnosis, multidisciplinary evaluation, and critical intraoperative decision-making when treating atypical sellar lesions.
Amol Raheja, Sumit Sinha, Neha Samson, Sanjeev Bhoi, Arulselvi Subramanian, Pushpa Sharma, and Bhawani Shankar Sharma
There has been increased interest in the potential importance of biochemical parameters as predictors of outcome in severe traumatic brain injury (sTBI).
Of 107 patients with sTBI (age 18–65 years with a Glasgow Coma Scale score of 4–8 presenting within 8 hours after injury) who were randomized for a placebo-controlled Phase II trial of progesterone with or without hypothermia, the authors serially analyzed serum biomarkers (S100-B, glial fibrillary acidic protein [GFAP], neuron-specific enolase [NSE], tumor necrosis factor–α, interleukin-6 [IL-6], estrogen [Eg], and progesterone [Pg]). This analysis was performed using the sandwich enzyme-linked immunosorbent assay technique at admission and 7 days later for 86 patients, irrespective of assigned group. The long-term predictive values of serum biomarkers for dichotomized Glasgow Outcome Scale (GOS) score, functional independence measure, and survival status at 6 and 12 months were analyzed using an adjusted binary logistic regression model and receiver operating characteristic curve.
A favorable GOS score (4–5) at 1 year was predicted by higher admission IL-6 (above 108.36 pg/ml; area under the curve [AUC] 0.69, sensitivity 52%, and specificity 78.6%) and Day 7 Pg levels (above 3.15 ng/ml; AUC 0.79, sensitivity 70%, and specificity 92.9%). An unfavorable GOS score (1–3) at 1 year was predicted by higher Day 7 GFAP levels (above 9.50 ng/ml; AUC 0.82, sensitivity 78.6%, and specificity 82.4%). Survivors at 1 year had significantly higher Day 7 Pg levels (above 3.15 ng/ml; AUC 0.78, sensitivity 66.7%, and specificity 90.9%). Nonsurvivors at 1 year had significantly higher Day 7 GFAP serum levels (above 11.14 ng/ml; AUC 0.81, sensitivity 81.8%, and specificity 88.9%) and Day 7 IL-6 serum levels (above 71.26 pg/ml; AUC 0.87, sensitivity 81.8%, and specificity 87%). In multivariate logistic regression analysis, independent predictors of outcome at 1 year were serum levels of Day 7 Pg (favorable GOS—OR 3.24, CI 1.5–7, p = 0.003; and favorable survival—OR 2, CI 1.2–3.5, p = 0.01); admission IL-6 (favorable GOS—OR 1.04, CI 1.00–1.08, p = 0.04); and Day 7 GFAP (unfavorable GOS—OR 0.79, CI 0.65–0.95, p = 0.01; and unfavorable survival—OR 0.80, CI 0.66–0.96, p = 0.01).
Serial Pg, GFAP, and IL-6 monitoring could aid in prognosticating outcomes in patients with acute sTBI. A cause and effect relationship or a mere association of these biomarkers to outcome needs to be further studied for better understanding of the pathophysiology of sTBI and for choosing potential therapeutic targets.
Clinical trial registration no.: CTRI/2009/091/000893 (http://www.ctri.nic.in).