Mark Iantosca

Bone morphogenetic proteins-2 and -4 attenuate apoptosis in a cerebellar primitive neuroectodermal tumor cell line

Similarities between primitive neuroectodermal tumors and central nervous system (CNS) progenitor cells have evoked interest in the response of these tumors to endogenous growth factors. The bone morphogenetic proteins (BMPs) have recently been found to regulate survival and differentiation of CNS progenitor cell populations. In this study, we investigated the effects of BMP‐2, BMP‐4, and BMP‐6 on the undifferentiated cerebellar primitive neuroectodermal tumor or medulloblastoma cell line DAOY. Analysis by reverse transcriptase‐polymerase chain reaction showed that mRNAs for type IA and type II BMP receptors were present in control cultures. In cultures treated with BMP‐2, mRNAs for BMP receptor type IB and the activin R‐I receptor became evident. Cultures were analyzed for total cell counts, proliferating cell nuclear antigen (PCNA), and apoptotic DNA fragmentation. There was a significant increase in total cell number in the BMP‐2 and BMP‐4 treatment groups, without any change in PCNA reactivity, and a dramatic decrease in the proportion of apoptotic nuclei at concentrations of BMP‐2 and BMP‐4 above 5 ng/ml (P < 0.001). These effects were not observed with BMP‐6, TGF‐β1 or GDNF. These results suggest that the increase in total cell number is due to the attenuation of apoptosis by BMP‐2 and BMP‐4. The anti‐apoptotic effect of BMP‐2 and BMP‐4 on this neuroectodermal cell line has potential clinical implications for neuroectodermal tumors. J. Neurosci. Res. 56:248–258, 1999.

Comparison of infection rate with the use of antibiotic-impregnated vs standard extraventricular drainage devices: a prospective, randomized controlled trial.

BACKGROUND External ventricular drainage (EVD) catheters provide reliable and accurate means of monitoring intracranial pressure and alleviating elevated pressures via drainage of cerebrospinal fluid (CSF). CSF infections occur in approximately 9% of patients. Antibiotic-impregnated (AI) EVD catheters were developed with the goal of reducing the occurrence of EVD catheter-related CSF infections and their associated complications. OBJECTIVE To present an international, prospective, randomized, open-label trial to evaluate infection incidence of AI vs standard EVD catheters. METHODS Infection was defined as (1) proven infection, positive CSF culture and positive Gram stain or (2) suspected infection: (A) positive CSF culture with no organisms identified on initial Gram stain; (B) negative CSF culture with a gram-positive or -negative stain; (C) CSF leukocytosis with a white blood cell/red blood cell count >0.02. RESULTS Four hundred thirty-four patients underwent implantation of an EVD catheter. One hundred seventy-six patients in the AI-EVD cohort and 181 in the standard EVD catheter cohort were eligible for evaluation of infection. The 2 groups were similar in all clinical characteristics. Proven infection was documented in 9 (2.5%) patients (AI: 4 [2.3%] vs standard: 5 [2.8%], P = 1.0). Suspected infection was documented in 31 (17.6%) patients receiving AI and 37 (20.4%) patients receiving standard EVD catheters, P = .504. Duration of time to suspected infection was prolonged in the AI cohort (8.8 ± 6.1 days) compared with the standard EVD cohort (4.6 ± 4.2 days), P = .002. CONCLUSION AI-EVD catheters were associated with an extremely low rate of catheter-related infections. AI catheters were not associated with risk reduction in EVD infection compared to standard catheters. Use of AI-EVD catheters is a safe option for a wide variety of patients requiring CSF drainage and monitoring, but the efficacy of AI-EVD catheters was not supported in this trial.

Results of endoscopic third ventriculostomy.

ETV is emerging as the treatment of choice for aqueductal stenosis caused by anatomic, inflammatory, and selected neoplastic etiologies. The technique has also proven useful in the pathologic diagnosis and treatment of these conditions. Long-term results of this procedure and comparison to standard shunting procedures are necessary to define indications for patients with pathologic findings in the intermediate response groups. Development of new studies for pre-operative assessment of CSF absorptive capacity and quantitative postoperative measures of ventriculostomy function would be invaluable additions to our ability to assess candidates for this procedure and their eventual outcome. Further study and technical refinements will, no doubt, lead to many more potential uses for these procedures in the treatment of hydrocephalus and its associated etiologies. The challenge for neuro-surgeons will be to define the operative indications and outcomes, while refining techniques for safely performing these useful procedures.

Primary intramedullary spinal cord germinoma: Case report

Primary intramedullary spinal cord germinoma (PISCG) is an exceedingly rare diagnosis, with fewer than 30 cases reported in the literature. It is even less common in the pediatric population. Usually, initial imaging at patient presentation reveals a mass. The authors describe the unique case of a child whose initial imaging showed only focal spinal cord atrophy, which was the earliest sign of a slowly growing intramedullary lesion that was eventually proven via biopsy to represent a PISCG. The authors outline this childs diagnostically challenging presentation, review the events leading up to a diagnosis, briefly discuss PISCG, and summarize their recommendations for other physicians who may encounter a similar case. They assert that PISCG should be considered as a rare entity in the differential diagnosis of progressive spinal cord dysfunction even in the absence of an MRI abnormality of an intrinsic spinal cord mass, especially if there is unexplained focal atrophy of the cord.

Impact of improved documentation on an academic neurosurgical practice

OBJECT Accuracy in documenting clinical care is becoming increasingly important; it can greatly affect the success of a neurosurgery department. As patient outcomes are being more rigorously monitored, inaccurate documentation of patient variables may present a distorted picture of the severity of illness (SOI) of the patients and adversely affect observed versus expected mortality ratios and hospital reimbursement. Just as accuracy of coding is important for generating professional revenue, accuracy of documentation is important for generating technical revenue. The aim of this study was to evaluate the impact of an educational intervention on the documentation of patient comorbidities as well as its impact on quality metrics and hospital margin per case. METHODS All patients who were discharged from the Department of Neurosurgery of the Penn State Milton S. Hershey Medical Center between November 2009 and June 2012 were evaluated. An educational intervention to improve documentation was implemented and evaluated, and the next 16 months, starting in March 2011, were used for comparison with the previous 16 months in regard to All Patient Refined Diagnosis-Related Group (APR-DRG) weight, SOI, risk of mortality (ROM), case mix index (CMI), and margin per discharge. RESULTS The APR-DRG weight was corrected from 2.123 ± 0.140 to 2.514 ± 0.224; the SOI was corrected from 1.8638 ± 0.0855 to 2.154 ± 0.130; the ROM was corrected from 1.5106 ± 0.0884 to 1.801 ± 0.117; and the CMI was corrected from 2.429 ± 0.153 to 2.825 ± 0.232, and as a result the average margin per discharge improved by 42.2%. The mean values are expressed ± SD throughout. CONCLUSIONS A simple educational intervention can have a significant impact on documentation accuracy, quality metrics, and revenue generation in an academic neurosurgery department.

Multifocal lymphangioendotheliomatosis with devastating intracranial hemorrhage

An in utero female was found to have a small hemorrhage at the foramen of Monro, hydrocephalus, and what was originally interpreted as a Dandy-Walker variant. At birth she had macrocephaly and numerous cutaneous, multifocal, red-pink blanchable macules. Postnatal MRI demonstrated a hemorrhagic soft-tissue mass involving the upper brainstem, thalamus, and basal ganglia most consistent with in utero complex multifocal intracranial hemorrhage. The skin lesions were thought to be consistent with multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT). The size and location of the hemorrhage precluded operative intervention, although the hydrocephalus was treated with a ventricular shunt. The child continues to have severe developmental delays. Multifocal lymphangioendotheliomatosis with thrombocytopenia is a multifocal vascular disorder most commonly involving the skin and gastrointestinal tract. Intracranial hemorrhages are rare in this context. This case is the third reported instance of MLT with associated intracranial hemorrhage and the only case described in the neurosurgical literature. The authors review the presenting features and pathophysiology of this condition.

A pivotal randomized clinical trial evaluating the safety and effectiveness of a novel hydrogel dural sealant as an adjunct to dural repair

BACKGROUND A watertight dural repair is critical to minimizing the risk of postoperative complications secondary to cerebrospinal fluid (CSF) leaks. OBJECTIVE To evaluate the safety and efficacy of a novel hydrogel, Adherus Dural Sealant, when compared with control, DuraSeal Dural Sealant System, as an adjunct to standard methods of dural repair. METHODS In this 17-center, prospective, randomized clinical trial designed as a noninferiority, single-blinded study, 124 patients received Adherus Dural Sealant (test sealant) and 126 received DuraSeal (control). The primary composite endpoint was the proportion of patients who were free of any intraoperative CSF leakage during Valsalva maneuver after dural repair, CSF leak/pseudomeningocele, and unplanned retreatment of the surgical site. Each component was then analyzed individually as a secondary endpoint. Patients were followed for 4 mo after surgery. RESULTS The primary composite endpoint at the 120-d follow-up was achieved in 91.2% of the test sealant group compared with 90.6% of the control, thus showing that the test sealant was statistically significantly noninferior to DuraSeal ( P = .0049). Post hoc analysis of the primary composite endpoint at 14 d demonstrated superiority of the test sealant over the control ( P = .030). Primary endpoint failures in the control group tended to occur early in follow-up period, while a majority of test dural sealant failures were identified through protocol-required radiographic imaging at the 120-d follow-up visit. CONCLUSION The test sealant, Adherus Dural Sealant, is a practical, safe, and effective adjunct to achieving a watertight dural closure after primary dural closure in cranial procedures.

Intracranial malignant peripheral nerve sheath tumor variant: an unusual neurovascular phenotype sarcoma case invading through the petrous bone

IntroductionIntracranial malignant peripheral nerve sheath tumor (MPNST) is exceedingly rare. Previously reported cases of intracranial MPNST have been associated with development within a prominent cranial nerve.MethodsThis is the first report of an MPNST with both nerve sheath and vascular phenotype that follows the neurovascular bundle, without arising in a major cranial nerve or in the setting of neurofibromatosis type 1 (NF1).ResultsThe patient is a 14-year-old boy with a history of worsening headaches for the past several months, left-sided hearing loss, nausea, vomiting, and vertigo. MRI was performed that demonstrated a large extra-axial tumor compressing the left infratemporal posterior temporal region. The tumor was associated with significant destruction of the superior portion of the petrous bone and extension through the petrous into the upper posterior fossa, immediately below the tentorium. The patient underwent surgical debulking and adjuvant chemotherapy with doxorubicin and ifosfamide. Pathology demonstrated a variant malignant peripheral nerve sheath tumor with both nerve sheath and vascular phenotype by immunostains. The patient’s symptoms improved following treatment.ConclusionWe present the first reported case of an intracranial MPNST variant that developed along the neurovascular bundle as a sarcoma with both nerve sheath and vascular phenotype through the petrous bone and not associated with a major cranial nerve or with stigmata of neurofibromatosis type 1 (NF1). Although this is an extremely unusual presentation due to location and lack of prominent cranial nerves in that location, it is not unusual for benign nerve sheath tumors to follow the neurovascular bundle through foramen of cortical long bone or pelvis. This case suggests that physicians should incorporate intracranial MPNST variant into their differential diagnosis in the cranium, even when tumor is not located near a prominent cranial nerve. Surgical debulking and adjuvant chemotherapy with doxorubicin and ifosfamide has led to improvement in patient symptoms.

Improving Responsiveness to Patient Phone Calls: A Pilot Study

Optimal patient-physician communication in the outpatient clinical setting is critical for safe and effective patient care. Keeping track of multiple patient telephone messages can be difficult and hazardous if a structured system is not in place. A multidisciplinary group at Hershey Medical Center developed a standardized approach for addressing patient telephone calls at their outpatient surgical clinics. This program was designed to improve the patient experience by providing a realistic time frame for phone calls to be returned and requests fulfilled. Additionally, this system permitted phone calls to be tracked and documented appropriately and allowed for prioritization of urgent and emergent messages. Our intent for this program was to close potential gaps within the communication chain at our outpatient surgical clinics, improve overall communication between clinicians and their patients, and improve both patient and employee satisfaction.

Pneumorrhachis Resulting in Transient Paresis after PICC Line Insertion into the Ascending Lumbar Vein

Obtaining intravascular access in the neonatal intensive care unit (NICU) is not only critical but also technically challenging. Malposition of the catheter tip is a known and well-documented complication. Specifically, peripherally inserted central venous catheter (PICC) line insertion into the ascending lumbar vein can lead to neurological dysfunction and, in some cases, even death. We present the first reported case of pneumorrhachis (PR) following PICC line insertion into the ascending lumbar vein. Our patient presented with lower extremity weakness and imaging confirmed the presence of air within the spinal canal. After conservative treatment, the strength deficit resolved and subsequent imaging revealed resolution of the air within the spinal canal. Insertion of central venous catheters into the ascending lumbar vein is a well-documented complication that can lead to neurologic injury and even death. This should be considered in the evaluation of any neonate presenting with an abnormal neurological examination or unexplained change in exam after line insertion.