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Ibrahim Hussain, Jean Anderson Eloy, Peter W. Carmel, and James K. Liu

Craniopharyngiomas are benign intracranial tumors that arise in the suprasellar and intrasellar region in children and adults. They are associated with calcification on neuroimaging, endocrinopathies, vision problems, and recurrence following subtotal resection. Molecular studies into their genetic basis have been limited, and therefore targeted medical therapies for this tumor have eluded physicians. With the discovery of aberrant Wnt/β-catenin pathway signaling in the pathogenesis of the most common subtype of craniopharyngioma (adamantinomatous), the identification of candidate genes and proteins implicated in this cascade provide attractive targets for future therapies. The recent development of a genetically engineered animal model of this tumor may also serve as a platform for evaluating potential therapies prior to clinical trials in humans. Advances in understanding the molecular pathogenesis of tumor recurrence have also been made, providing clues to develop adjuvant and neoadjuvant therapies to couple with tumor resection for optimal response rates. Finally, advances in genomic technologies and next-generation sequencing will underlie the translation of these genetic and molecular studies from the bench to clinical practice. In this review, the authors present an analysis of the molecular oncogenesis of craniopharyngioma and current directions in the development of novel therapies for these morbid, yet poorly understood brain tumors.

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Peyton L. Nisson, Ibrahim Hussain, Roger Härtl, Samuel Kim, and Ali A. Baaj

OBJECTIVE

An arachnoid web of the spine (AWS) is a rare and oftentimes challenging lesion to diagnose, given its subtle radiographic findings. However, when left untreated, this lesion can have devastating effects on a patient’s neurological function. To date, only limited case reports and series have been published on this topic. In this study, the authors sought to better describe this lesion, performing a systematic literature review and including 2 cases from their institution’s experience.

METHODS

A systematic literature search was performed in September 2018 that queried Ovid MEDLINE (1946–2018), PubMed (1946–2018), Wiley Cochrane Library: Central Register of Controlled Trials (1898–2018), and Thompson Reuters Web of Science: Citation Index (1900–2018), per PRISMA guidelines. Inclusion criteria specified all studies and case reports of patients with an AWS in which any relevant surgery types were considered and applied. Studies on arachnoid cysts and nonhuman populations, and those that did not report patient treatments or outcomes were excluded from the focus review.

RESULTS

A total of 19 records and 2 patients treated by the senior authors were included in the systematic review, providing a total of 43 patients with AWS. The mean age was 52 years (range 28–77 years), and the majority of patients were male (72%, 31/43). A syrinx was present in 67% (29/43) of the cases. All AWSs were located in the thoracic spine, and all but 2 (95%) were located dorsally (1 ventrally and 1 circumferentially). Weakness was the most frequently reported symptom (67%, 29/43), followed by numbness and/or sensory loss (65%, 28/43). Symptoms predominated in the lower extremities (81%, 35/43). It was found that nearly half (47%, 20/43) of patients had been experiencing symptoms for 1 year or longer before surgical intervention was performed, and 35% (15/43) of reports stated that symptoms were progressive in nature. The most commonly used surgical technique was a laminectomy with intradural excision of the arachnoid web (86%, 36/42). Following surgery, 91% (39/43) of patients had reported improvement in their neurological symptoms. The mean follow-up was 9.2 months (range 0–51 months).

CONCLUSIONS

AWS of the spine can be a debilitating disease of the spine with no more than an indentation of the spinal cord found on advanced imaging studies. The authors found this lesion to be reported in twice as many males than females, to be associated with a syrinx more than two-thirds of the time, and to only have been reported in the thoracic spine; over 90% of patients experienced improvement in their neurological function following surgery.

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John K. Chae, Neelan J. Marianayagam, Ibrahim Hussain, Amanda Cruz, Ali A. Baaj, Roger Härtl, and Jeffrey P. Greenfield

BACKGROUND

The authors assessed the connection between clinical outcomes and morphometrics in patients with complex Chiari malformation (CM) who have undergone posterior fossa decompression (PFD) and subsequent occipitocervical fusion (OCF) with or without ventral decompression (VD).

OBSERVATIONS

The authors retrospectively reviewed 33 patients with CM aged over 21 years who underwent PFD and OCF with or without endoscopic endonasal odontoidectomy at the authors’ institution (21 OCF only and 12 OCF + VD). Clivoaxial angle (CXA), pB-C2 (perpendicular line to the line between the basion and C2), atlantodental interval (ADI), basion-dens interval (BDI), basion-axial interval (BAI), and C1 canal diameter were measured on preoperative and approximately 3-month postoperative computed tomography or magnetic resonance imaging scans. Common symptoms included headache, paresthesia, and bulbar symptoms. Clinical improvement after surgery was observed in 78.8% of patients. CXA, ADI, and BDI all significantly increased after surgery, whereas pB-C2 and BAI significantly decreased. OCF + VD had a significantly more acute CXA and longer pB-C2 preoperatively than OCF only. Patients who clinically improved postoperatively showed the same significant morphometric changes, but those who did not improve showed no significant morphometric changes.

LESSONS

Patients showing improvement had greater corrections in skull base morphometrics than those who did not. Although there are various mutually nonexclusive reasons why certain patients do not improve after surgery, smaller degrees of morphometric correction could play a role.

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Neelan J. Marianayagam, John K. Chae, Ibrahim Hussain, Amanda Cruz, Ali A. Baaj, Roger Härtl, and Jeffrey P. Greenfield

BACKGROUND

The authors analyzed the pre- and postoperative morphometric properties of pediatric patients with complex Chiari malformation undergoing occipitocervical fusion (OCF) to assess clinical outcomes and morphometric properties that might influence postoperative outcomes.

OBSERVATIONS

The authors retrospectively reviewed 35 patients younger than 22 years with Chiari malformation who underwent posterior fossa decompression and OCF with or without endoscopic endonasal odontoidectomy at their institution (13 with and 22 without odontoidectomy). Clivo-axial angle (CXA), pB-C2, atlantodental interval, basion-dens interval, basion-axial interval, and canal diameter at the level of C1 were measured on preoperative and approximately 3-month postoperative computed tomography or magnetic resonance imaging. The authors further stratified the patient cohort into three age groups and compared the three cohorts. The most common presenting symptoms were headache, neck/shoulder pain, and dysphagia; 80% of the cohort had improved clinical outcomes. CXA increased significantly after surgery. When stratified into those who showed postoperative improvement and those who did not, only the former showed a significant increase in CXA. After age stratification, the significant changes in CXA were observed in the 7- to 13-year-old and 14- to 21-year-old cohorts.

LESSONS

CXA may be the most important morphometric predictor of clinical outcomes after OCF in pediatric patients with complex Chiari malformation.

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Ibrahim Hussain, Qasim Husain, Soly Baredes, Jean Anderson Eloy, Robert W. Jyung, and James K. Liu

Paragangliomas are rare, slow-growing tumors that frequently arise in the head and neck, with the carotid bodies and temporal bone of the skull base being the most common sites. These neoplasms are histologically similar to pheochromocytomas that form in the adrenal medulla and are divided into sympathetic and parasympathetic subtypes based on functionality. Skull base and head and neck region paragangliomas (SHN-PGs) are almost always derived from parasympathetic tissue and rarely secrete catecholamines. However, they can cause significant morbidity by mass effect on various cranial nerves and major blood vessels. While surgery for SHN-PG can be curative, postoperative deficits and recurrences make these lesions challenging to manage. Multiple familial syndromes predisposing individuals to development of paragangliomas have been identified, all involving mutations in the succinate dehydrogenase complex of mitochondria. Mutations in this enzyme lead to a state of “pseudohypoxia” that upregulates various angiogenic, survival, and proliferation factors. Moreover, familial paraganglioma syndromes are among the rare inherited diseases in which genomic imprinting occurs. Recent advances in gene arrays and transcriptome/exome sequencing have identified an alternate mutation in sporadic SHN-PG, which regulates proto-oncogenic pathways independent of pseudohypoxia-induced factors. Collectively these findings demonstrate that paragangliomas of the skull base and head and neck region have a distinct genetic signature from sympathetic-based paragangliomas occurring below the neck, such as pheochromocytomas. Paragangliomas serve as a unique model of primarily surgically treated neoplasms whose future will be altered by the elucidation of their genomic complexities. In this review, the authors present an analysis of the molecular genetics of SHN-PG and provide future directions in patient care and the development of novel therapies.

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Constantin Tuleasca, Yohan Ducos, Marc Levivier, Fabrice Parker, and Nozar Aghakhani

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Jacob L. Goldberg, Ibrahim Hussain, Joseph A. Carnevale, Alexandra Giantini-Larsen, Ori Barzilai, and Mark H. Bilsky

OBJECTIVE

Paraspinal ganglioneuromas are rare tumors that arise from neural crest tissue and can cause morbidity via compression of adjacent organs and neurovascular structures. The authors investigated a case series of these tumors treated at their institution to determine clinical outcomes following resection.

METHODS

A retrospective review of a prospectively collected cohort of consecutive, pathology-confirmed, surgically treated paraspinal ganglioneuromas from 2001 to 2019 was performed at a tertiary cancer center.

RESULTS

Fifteen cases of paraspinal ganglioneuroma were identified: 47% were female and the median age at the time of surgery was 30 years (range 10–67 years). Resected tumors included 9 thoracic, 1 lumbar, and 5 sacral, with an average maximum tumor dimension of 6.8 cm (range 1–13.5 cm). Two patients had treated neuroblastomas that matured into ganglioneuromas. One patient had a secretory tumor causing systemic symptoms. Surgical approaches were anterior (n = 11), posterior (n = 2), or combined (n = 2). Seven (47%) and 5 (33%) patients underwent gross-total resection (GTR) or subtotal resection with minimal residual tumor, respectively. The complication rate was 20%, with no permanent neurological deficits or deaths. No patient had evidence of tumor recurrence or progression after a median follow-up of 68 months.

CONCLUSIONS

Surgical approaches and extent of resection for paraspinal ganglioneuromas must be heavily weighed against the advantages of aggressive debulking and decompression given the complication risk of these procedures. GTR can be curative, but even patients without complete tumor removal can show evidence of excellent long-term local control and clinical outcomes.

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Ibrahim Hussain, Ori Barzilai, Anne S. Reiner, Lily McLaughlin, Natalie M. DiStefano, Shahiba Ogilvie, Anne L. Versteeg, Charles G. Fisher, Mark H. Bilsky, and Ilya Laufer

OBJECTIVE

The Spinal Instability Neoplastic Score (SINS) correlates with preoperative disability and response to stabilization, with patients with higher scores experiencing greater relief after surgery. However, there is a paucity of data demonstrating the extent to which each component contributes to preoperative clinical status and response to stabilization surgery. The objectives of this study were 2-fold. First, to determine how SINS components correlate with pre- and postoperative patient-reported outcomes (PROs). Second, to determine whether patients with higher SINS (10–12) in the “indeterminate” group respond differently to surgery compared to patients with lower SINS (7–9).

METHODS

SINS and PROs were prospectively collected in 131 patients undergoing stabilization surgery for metastatic spinal disease. Association of SINS components and their individual scores with preoperative symptom burden and PRO symptom change after surgery was analyzed using the Spearman rank correlation coefficient (rho) and the Kruskal-Wallis test. SINS and association with preoperative PRO scores and mean differences in post- and preoperative PRO scores were compared for 2 SINS categories within the indeterminate group (7–9 vs 10–12) using the Wilcoxon 2-sample test and Wilcoxon signed-rank test.

RESULTS

The presence of mechanical pain, followed by metastatic location, correlated most strongly with preoperative functional disability measures and lower disability PRO scores following surgical stabilization. Blastic rather than lytic bone lesions demonstrated stronger association with pain reduction following stabilization. Following surgery, patients with SINS 10–12 demonstrated markedly greater improvement in pain and disability PRO scores nearly across the board compared to patients with SINS 7–9.

CONCLUSIONS

The presence of mechanical pain has the strongest correlation with preoperative disability and improvement in pain and disability PRO scores after surgery. Radiographic components of SINS also correlate with preoperative symptom severity and postoperative PRO, supporting their utilization in evaluation of spinal instability. Among patients with indeterminate SINS, patients with higher scores experience greater reduction in pain and disability PRO scores following surgical stabilization, suggesting that the indeterminate-SINS group includes distinct populations.

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Praveen V. Mummaneni, Ibrahim Hussain, Christopher I. Shaffrey, Robert K. Eastlack, Gregory M. Mundis Jr., Juan S. Uribe, Richard G. Fessler, Paul Park, Leslie Robinson, Joshua Rivera, Dean Chou, Adam S. Kanter, David O. Okonkwo, Pierce D. Nunley, Michael Y. Wang, Frank La Marca, Khoi D. Than, Kai-Ming Fu, and the International Spine Study Group

OBJECTIVE

Minimally invasive surgery (MIS) for spinal deformity uses interbody techniques for correction, indirect decompression, and arthrodesis. Selection criteria for choosing a particular interbody approach are lacking. The authors created the minimally invasive interbody selection algorithm (MIISA) to provide a framework for rational decision-making in MIS for deformity.

METHODS

A retrospective data set of circumferential MIS (cMIS) for adult spinal deformity (ASD) collected over a 5-year period was analyzed by level in the lumbar spine to identify surgeon preferences and evaluate segmental lordosis outcomes. These data were used to inform a Delphi session of minimally invasive deformity surgeons from which the algorithm was created. The algorithm leads to 1 of 4 interbody approaches: anterior lumbar interbody fusion (ALIF), anterior column release (ACR), lateral lumbar interbody fusion (LLIF), and transforaminal lumbar interbody fusion (TLIF). Preoperative and 2-year postoperative radiographic parameters and clinical outcomes were compared.

RESULTS

Eleven surgeons completed 100 cMISs for ASD with 338 interbody devices, with a minimum 2-year follow-up. The type of interbody approach used at each level from L1 to S1 was recorded. The MIISA was then created with substantial agreement. The surgeons generally preferred LLIF for L1–2 (91.7%), L2–3 (85.2%), and L3–4 (80.7%). ACR was most commonly performed at L3–4 (8.4%) and L2–3 (6.2%). At L4–5, LLIF (69.5%), TLIF (15.9%), and ALIF (9.8%) were most commonly utilized. TLIF and ALIF were the most selected approaches at L5–S1 (61.4% and 38.6%, respectively). Segmental lordosis at each level varied based on the approach, with greater increases reported using ALIF, especially at L4–5 (9.2°) and L5–S1 (5.3°). A substantial increase in lordosis was achieved with ACR at L2–3 (10.9°) and L3–4 (10.4°). Lateral interbody arthrodesis without the use of an ACR did not generally result in significant lordosis restoration. There were statistically significant improvements in lumbar lordosis (LL), pelvic incidence–LL mismatch, coronal Cobb angle, and Oswestry Disability Index at the 2-year follow-up.

CONCLUSIONS

The use of the MIISA provides consistent guidance for surgeons who plan to perform MIS for deformity. For L1–4, the surgeons preferred lateral approaches to TLIF and reserved ACR for patients who needed the greatest increase in segmental lordosis. For L4–5, the surgeons’ order of preference was LLIF, TLIF, and ALIF, but TLIF failed to demonstrate any significant lordosis restoration. At L5–S1, the surgical team typically preferred an ALIF when segmental lordosis was desired and preferred a TLIF if preoperative segmental lordosis was adequate.