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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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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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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.