A Systematic Review of Sellar and Parasellar Brown Tumors: An Analysis of Clinical, Diagnostic, and Management Profiles.

OBJECTIVE: To systematically review and analyze clinical, diagnostic, and management trends in sellar and parasellar brown tumors reported in existing literature. METHODS: In this systematic review, PubMed, Ovid MEDLINE, Scopus, and Google Scholar databases were searched for reported cases of sellar/parasellar brown tumors. Relevant titles and abstracts were screened in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. Articles meeting inclusion criteria were subjected to data extraction, summarization, and analysis. A rare case of parasellar brown tumor was also presented. RESULTS: Eight reports (including the current report) were eligible for inclusion. Mean patient age was 42.75 years. Reported symptoms included visual disturbances (n = 6), headache (n = 5), fatigue (n = 3), nausea/vomiting (n = 2), chest pain (n = 1), neck pain (n = 1), and dysphagia (n = 1). In cases where computed tomography findings were provided (n = 6), lesions were noted to be expansile and lytic. Lesions were hyperintense on T2-weighted magnetic resonance imaging (66.7%) and demonstrated contrast enhancement (83.3%). Histology unanimously showed multinucleated giant cells in a fibrovascular connective tissue stroma. Dramatic symptom resolution was noted in all patients who underwent resection of the sellar/parasellar brown tumor (n = 4; 50%). CONCLUSIONS: Sellar/parasellar brown tumors are a rare, tertiary manifestation of hyperparathyroidism and can be elusive to diagnose. Diagnosis requires a high index of clinical suspicion in addition to comprehensive biochemical testing, imaging, and histopathologic analysis. Surgical extirpation is favored in cases where the lesion is causing compressive symptoms, or if it is unresponsive to management of hyperparathyroidism.

The role of the immune system in brain metastasis.

Metastatic brain tumors are the most common brain tumors in adults. With numerous successful advancements in systemic treatment of most common cancer types, brain metastasis is becoming increasingly important in the overall prognosis of cancer patients. Brain metastasis of peripheral tumor is the result of complex interplay of primary tumor, immune system and central nervous system microenvironment. Once formed, brain metastases hide behind the blood brain barrier and become inaccessible to chemotherapies that are otherwise successful in targeting systemic cancer. The approval of immune checkpoint inhibitors for several common cancers such as advanced melanoma and lung cancers brings with it the opportunity and obligation to further understand the mechanisms of immunosuppression by tumors that spread to the brain as well as the interaction between the brain environment and tumor microenvironment. In this review paper we define the central role of the immune system in the development of brain metastases. We performed a comprehensive review of the literature to outline the molecular mechanisms of immunosuppression used by tumors and how the immune system interacts with the central nervous system to facilitate brain metastasis. In particular we discuss the tumor-type-specific mechanisms of metastasis of cancers that preferentially metastasize to the brain as well as the therapies that effectively modulate the immune response, such as immune checkpoint inhibitors and vaccines.

The efficacy of routine use of recombinant human bone morphogenetic protein-2 in occipitocervical and atlantoaxial fusions of the pediatric spine: a minimum of 12 months' follow-up with computed tomography.

OBJECT The purpose of this study focusing on fusion rate was to determine the efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2) use in posterior instrumented fusions of the craniocervical junction in the pediatric population. The authors previously reported the short-term (mean follow-up 11 months) safety and efficacy of rhBMP-2 use in the pediatric age group. The present study reports on their long-term results (minimum of 12 months' follow-up) and focuses on efficacy. METHODS The authors performed a retrospective review of 83 consecutive pediatric patients who had undergone posterior occipitocervical or atlantoaxial spine fusion at Texas Children's Hospital or Riley Children's Hospital during the period from October 2007 to October 2012. Forty-nine patients were excluded from further analysis because of death, loss to follow-up, or lack of CT evaluation of fusion at 12 or more months after surgery. Fusion was determined by postoperative CT scan at a minimum of 12 months after surgery. The fusion was graded and classified by a board-certified fellowship-trained pediatric neuroradiologist. Other factors, such as patient age, diagnosis, number of vertebral levels fused, use of allograft or autograft, dosage of bone morphogenetic protein (BMP), and use of postoperative orthosis, were recorded. RESULTS Thirty-four patients had a CT scan at least 12 months after surgery. The average age of the patients at surgery was 8 years, 1 month (range 10 months-17 years). The mean follow-up was 27.7 months (range 12-81 months). There were 37 fusion procedures in 34 patients. Solid fusion (CT Grade 4 or 4-) was achieved in 89.2% of attempts (33 of 37), while incomplete fusion or failure of fusion was seen in 10.8%. Based on logistic regression analysis, there was no significant association between solid fusion and age, sex, BMP dose, type of graft material, use of postoperative orthosis, or number of levels fused. Three of 34 patients (8.8%) required revision surgery. CONCLUSIONS Despite the large number of adult studies reporting positive effects of BMP on bone fusion, our long-term outcomes using rhBMP-2 in the pediatric population suggest that rates of fusion failure are higher than observed in contemporary adult and pediatric reports of occipitocervical and atlantoaxial spine fusions.

Electrical stimulation and testosterone enhance recovery from recurrent laryngeal nerve crush.

OBJECTIVE: This study investigated the effects of a combinatorial treatment, consisting of a brief period of nerve electrical stimulation (ES) and systemic supraphysiologic testosterone, on functional recovery following a crush of the recurrent laryngeal nerve (RLN). STUDY DESIGN: Prospective, controlled animal study. METHODS: After a crush of the left RLN, adult male Sprague-Dawley rats were divided into four treatment groups: 1) no treatment, 2) ES, 3) testosterone propionate (TP), and 4) ES + TP. Each group was subdivided into 1, 2, 3, or 4 weeks post-operative survival time points. Groups had an n of 4- 9. Recovery of vocal fold mobility (VFM) was assessed. RESULTS: Brief ES of the proximal nerve alone or in combination with TP accelerated the initiation of functional recovery. TP administration by itself also produced increased VFM scores compared to controls, but there were no statistical differences between the ES-treated and TP-treated animals. Treatment with brief ES alone was sufficient to decrease the time required to recover complete VFM. Animals with complete VFM were seen in treatment groups as early as 1 week following injury; in the untreated group, this was not observed until at least 3 weeks post-injury, translating into a 66% decrease in time to complete recovery. CONCLUSIONS: Brief ES, alone or in combination with TP, promise to be effective therapeutic interventions for promoting regeneration following RLN injury.

Androgen treatment and recovery of function following recurrent laryngeal nerve injury in the rat.

PURPOSE: To investigate the effects of the androgen testosterone propionate (TP), on regeneration of the recurrent laryngeal nerve (RLN) after unilateral crush injury using assessment of vocal fold mobility (VFM) as a measure of behavioral recovery. METHODS: 48 adult male rats underwent standardized crush injury of left RLN and received treatment in the form of 2 silastic capsules containing TP or controls receiving a blank capsule (untreated). Direct laryngoscopic assessment of vocal cord mobility was performed before, immediately following and 1, 2, 3, 4, 5 or 6 weeks post injury. RESULTS: Treatment with TP enhanced the recovery of full VFM following crush injury of the RLN compared to controls. There was statistically significant improvement in VFM seen at the 1 and 2 week time points (p < 0.05). By 4 weeks TP-treated rats displayed a 100% recovery of VFM function, compared to only 50% by the control group. CONCLUSIONS: TP enhances RLN functional recovery following a crush injury, which further supports its potential general applicability as a therapeutic agent in peripheral nerve injury.

A rat model for intracranial facial nerve crush injuries.

OBJECTIVE: (1) Explain the need for an animal model to study intracranial injuries to the facial nerve. (2) Describe various techniques attempted to identify and crush the intracranial segment of the facial nerve in a rat model. (3) Describe in detail a successful rat model of intracranial facial nerve crush injury. STUDY DESIGN: Randomized controlled animal study. SETTING: Animal laboratory. SUBJECTS AND METHODS: Multiple attempts at surgical approaches to the cerebellopontine angle were attempted on cadaveric rats. Once a successful approach was derived, this was used on 19 live rats under anesthesia. Fourteen rats had a 1-minute facial nerve crush performed, and 5 had a sham surgery with complete surgical exposure of the facial nerve but no crush. Rats were followed for a 12-week duration evaluating immediate postoperative facial nerve function, complications, and survival. RESULTS: All 14 (100%) rats that underwent surgery with crush injury had complete facial paralysis postoperatively. Complete facial paralysis was defined as loss of eye-blink reflex, flat vibrissae, and lack of vibrissae movement. The 5 sham surgery rats had complete facial function postoperatively. Surgery was performed by 2 separate surgeons with no difference in outcome between the 2. Complications occurred in only 1 animal (1/19, 5.3%), which was a corneal abrasion requiring sacrifice. CONCLUSION: Our group describes a consistent method for performing an intracranial crush injury in the rat. This new model and its applications in translational facial nerve research are promising, particularly with tumors or lesions at the cerebellopontine angle.