Lorenzo F. Munoz

Genomic Expression Discovery Predicts Pathways and Opposing Functions behind Phenotypes

Discovering states of genetic expression that are true to a high degree of certainty is likely to predict gene function behind biological phenotypes. The states of expression (up- or down-regulated) of 19,200 cDNAs in 10 meningiomas are compared with normal brain by an algorithm that detects only 1 false measurement per 192,000; 364 genes are discovered. The expression data accurately predict activation of signaling pathways and link gene function to specific phenotypes. Meningiomas appear to acquire aberrant phenotypes by disturbing the balanced expression of molecules that promote opposing functions. The findings expose interconnected genes and propose a role of genomic expression discovery in functional genomics of living systems.

Neuro-Critical Care Skills Training Using a Human Patient Simulator

BackgroundNeurosurgical trainees regularly encounter critical care situations. Traditionally, education was accomplished through lecture and experience. Increasingly, human patient simulators (HPS) are employed, allowing trainees to sharpen skills in a safe and realistic environment. We describe our experience using HPS in neurosurgical training.MethodsWe developed a critical care training program for residents and medical students using HPS. We used a hi-fidelity, lifelike Human Patient Simulator™ (HPS™) produced by Medical Education Technologies, Inc.™ to simulate realistic scenarios for trainee education. Topics included spinal shock, closed head injury, and cerebral vasospasm. A three-way evaluation model was employed to test validity, including pre- and post-exercise testing, survey feedback, and videotaped replay. The simulation exercises were conducted by a neuro-critical care attending, a senior neurosurgical resident, and a HPS technician.ResultsWe currently have 29 participants. On a 20-point critical care multiple-choice exam for these participants, average improvement has been 4.5 points or 25%. In subgroup analysis, average improvement was 4.75 points (24%) amongst neurosurgery residents, 3.07 points (18%) amongst neurology residents, 7 points (38%) amongst general surgery residents, and 7 points (38%) amongst senior medical students. Post-exercise evaluations were overwhelmingly positive.ConclusionsNeurosurgical critical care education is important for safe and effective care for patients. Clinical experience and didactic lectures help trainees obtain a solid knowledge base, but do not provide the benefit for learning in a fail-safe environment. Through the use of HPS, we have enhanced the critical care education of our trainees.

Mathematical modeling of noise and discovery of genetic expression classes in gliomas.

The microarray array experimental system generates noisy data that require validation by other experimental methods for measuring gene expression. Here we present an algebraic modeling of noise that extracts expression measurements true to a high degree of confidence. This work profiles the expression of 19 200 cDNAs in 35 human gliomas; the experiments are designed to generate four replicate spots/gene with switching of probes. The validity of the extracted measurements is confirmed by: (1) cluster analysis that generates a molecular classification differentiating glioblastoma from lower-grade tumors and radiation necrosis; (2) By what other investigators have reported in gliomas using paradigms for assaying molecular expression other than gene profiling; and (3) Real-time RT–PCR. The results yield a genetic analysis of gliomas and identify classes of genetic expression that link novel genes to the biology of gliomas.

Multidisciplinary treatment of olfactory neuroblastoma: Patterns of failure and management of recurrence ☆

PURPOSE Esthesioneuroblastoma is an uncommon malignancy of the head and neck for which there is no defined treatment protocol. The purpose of this study is to report our experience with the treatment and patterns of failure of this disease. METHODS AND MATERIALS From 1994 to 2012, 37 previously unreported patients with esthesioneuroblastoma were evaluated, and 32 eventually treated for cure at 2 academic medical centers. All patients were staged with Kadish criteria. The mean and median follow-ups were 96.1 and 76.5 months respectively (range 6-240 months). RESULTS The Kadish stage was A in 6 patients, B in 13 patients, and C in 13 patients. Four patients were initially treated with concurrent chemo-radiation therapy. Twenty-eight patients were treated with primary surgery. Two (2) underwent open medial maxillectomy and 26 underwent craniofacial resection (open - 17, endoscopic - 9). Three patients received curative surgical resection only. Seven patients failed either within the cranial axis or distantly, 6 of the 7 are dead of disease, 10-194 months following initial treatment. Six patients had isolated neck recurrences, 4/6 were salvaged with neck dissection and additional chemo-radiation and remain alive 30-194 months following initial treatment. Estimated overall survival rate at 10 years was 78% based on Kadish and T stages. CONCLUSION In this retrospective analysis of 32 patients, Kadish stage C and stage T3/T4 tumors were associated with worse outcome. Total radiation dose of 60 Gy, margin status, patient age, were not found to have significant prognostic value.

Surgical treatment of cerebellar metastases

Background: Cerebral metastases are a common neurosurgical finding. Surgery confers several advantages to other therapies, including immediate symptomatic improvement, diagnosis, and relief from corticosteroid dependence. Here we evaluate patients with cerebellar metastases who underwent surgery and compare their findings to those in the literature, and address the benefit of avoiding ventriculo-peritoneal shunting in patients undergoing surgery. Methods: We performed a retrospective analysis involving 50 patients with cerebellar metastases who underwent surgical resection. Ventriculo-peritoneal shunts were placed in patients necessitating permanent CSF drainage. We evaluated presentation, diagnosis, complications, and outcome. Results: Our review included 21 males and 29 females, 29 to 82 years of age. Primary tumors included lung (48%), breast (14%), GI (14%), endometrial/ovarian (6%), melanoma (6%), sarcoma (4%), lymphoma (4%), laryngeal (2%), and other (2%). Clinical symptoms at presentation commonly were those secondary to elevated intracranial pressure and were the initial complaint in 34% of patients. Preoperatively, 29 patients were noted to have hydrocephalus. Importantly, 76% of these patients were able to avoid placement of a ventriculo-peritoneal shunt following surgery. Only two complications were noted in our series of 50 patients, including a symptomatic pseudomeningocele and a wound infection. No symptomatic postoperative hematoma developed in any surgical case. Conclusion: A review of the literature has shown a high complication rate in patients undergoing surgical resection of cerebellar metastases. We have shown that surgical resection of cerebellar metastases is a safe procedure and is effective in the treatment of hydrocephalus in the majority of patients harboring cerebellar lesions.

Outcome following intracranial hemorrhage associated with novel oral anticoagulants

The emergence of dabigatran, rivaroxaban and apixaban has changed the approach to anticoagulation for patients worldwide. Continued approval of novel oral anticoagulants (NOAC) for non-valvular atrial fibrillation and venous thromboembolism will result in increasing use of these medications over warfarin. Morbidity and mortality of anticoagulant related intracranial hemorrhage (ICH) is relatively high and there is concern that outcomes may be worse with NOAC as there is a lack of specific antidotes for these agents with a greater risk for hematoma expansion. Unfortunately, the evidence supporting effective reversal strategies is lacking. Therefore, to gain further insight into the outcome after the management of NOAC related ICH, we present our experience with two patients with NOAC-induced ICH.

Ventriculoperitoneal shunt with a rare twist: small-bowel ischemia and necrosis secondary to knotting of peritoneal catheter

Small-bowel ischemia and necrosis due to knotting of the peritoneal catheter is an extremely rare complication related to a ventriculoperitoneal shunt (VPS). A 3-month-old girl, with a history of Chiari II malformation and myelomeningocele (MM) after undergoing right occipital VPS insertion and MM repair at birth, presented to the emergency department with a high-grade fever. Examination of a CSF sample obtained via shunt tap raised suspicion for the presence of infection. Antibiotic therapy was initiated, and subsequently the VPS was removed and an external ventricular drain was placed. Intraoperatively, as attempts at pulling the distal catheter from the scalp incision were met with resistance, the distal catheter was cut and left in the abdomen while the remainder of the shunt system was successfully removed. While the patient was awaiting definitive shunt revision surgery to replace the VPS, she developed abdominal distension due to small-bowel obstruction. An emergency exploratory laparotomy revealed a knot in the distal catheter looping around and strangulating the distal ileum, causing small-bowel ischemia and necrosis in addition to the obstruction. A small-bowel resection with ileostomy was performed, with subsequent placement of ventriculoatrial shunt for treatment of hydrocephalus. The authors report this exceedingly rare clinical scenario to highlight the fact that any retained distal catheter must be carefully managed with immediate abdominal exploration to remove the distal catheter to avoid bowel necrosis as pulling of a knotted peritoneal catheter may strangulate the bowel and cause ischemia, with significant clinical morbidity and possible mortality.

Stereotactic radiosurgery boost to the resection cavity for cerebral metastases: Report of overall survival, complications, and corticosteroid protocol

Background: This report focuses on the overall survival and complications associated with treatment of cerebral metastases with surgical resection followed by stereotactic radiosurgery (SRS). Management and complications of corticosteroid therapy are underreported in the literature but represent an important source of morbidity for patients. Methods: Fifty-nine consecutive patients underwent surgical resection of a cerebral metastasis followed by SRS to the cavity. Patient charts were reviewed retrospectively to ascertain overall survival, local control, surgical complications, SRS complications, and corticosteroid complications. Results: Our mean follow-up was 14.4 months (median 12.0 months, range 0.9-62.9 months). Median overall survival in this series was 15.25 months and local control was 98.3%. There was a statistically significant survival benefit conferred by Radiation Therapy Oncology Group recursive partitioning analysis Classes 1 and 2. The surgical complication rate was 6.8% while the SRS complication rate was 2.4%. Corticosteroid complications are reported and dependence at 1 month was 20.3%, at 3 months 6.8%, at 6 months 1.7%, and at 12 months no patients remained on corticosteroid therapy. Conclusions: Overall survival and local control with this treatment paradigm compare well to the other published literature. Complications associated with this patient population are low. A corticosteroid tapering protocol is proposed and demonstrated lower rates of steroid-related complications and dependence than previously reported.

Minimally invasive evacuation of intraventricular hemorrhage with the Apollo vibration/suction device.

Intraventricular hemorrhages (IVH) can occur as a consequence of spontaneous intracerebral hemorrhage, aneurysm rupture, arteriovenous malformation hemorrhage, trauma, or coagulopathy. IVH is a known risk factor for poor clinical outcome with up to 80% mortality. The current standard treatment strategy for IVH consists of the placement of an external ventricular drain. We report our early experience with using the Apollo suction/vibration aspiration system (Penumbra, Alameda, CA, USA) for minimally invasive evacuation of IVH with a review of the pertinent literature. Medical records of patients with IVH who were admitted to Rush University Medical Center, USA, from July to November 2014 were queried from the electronic database. Patients with Graeb Scores (GS) >6 were selected for minimally invasive IVH evacuation with the Apollo aspiration system. Patient demographics, pre- and post-operative GS, pre- and post-operative modified Graeb Score (mGS), as well procedure related complications were analyzed and recorded. A total of eight patients (five men) were identified during the study period. The average age was 55.5years. The mean GS was 9.6 pre-operatively and decreased to 4.9 post-operatively (p=0.0002). The mean mGS was 22.9 pre-operatively and decreased to 11.4 post-operatively (p=0.0001). Most of the IVH reduction occurred in the frontal horn and atrium of the lateral ventricle, as well the third ventricle. One (1/8) procedure-related complication occurred consisted of a tract hemorrhage. The Apollo system can be used for minimally invasive IVH evacuation to achieve significant blood clot volume reduction with minimal procedure-related complication.

Hyperdense suprasellar mass: An unusual radiological presentation of intracranial dermoid cyst.

We report an exceedingly rare patient with a hyperdense suprasellar dermoid cyst and a pertinent review of the literature. Intracranial dermoid tumors are rare congenital lesions of the brain that account for less than 1% of all intracranial tumors. Even though they are rare, typical CT scan and MRI features and location allow radiological diagnosis in the majority of patients. Radiologically, dermoid cysts typically present as low density masses on CT scan and are generally hyperintense on T1-weighted MRI sequences with variable signal on T2-weighted sequences. The recognition of atypical features can avoid diagnostic pitfalls and is clinically relevant for overall surgical management.