Thomas Wilson, MD

Abstract

BACKGROUND: Cervical dystonia is a disabling medical condition that drastically decreases quality of life. Surgical treatment consists of peripheral nerve denervation procedures with or without myectomies or deep brain stimulation (DBS). The current objective was to compare the efficacy of peripheral denervation versus DBS in improving severity of cervical dystonia through a systematic review and meta-analysis.METHODS: A search of PubMed, MEDLINE, EMBASE and Web of Science electronic databases was conducted in accordance with PRISMA guidelines. Pre- and post-operative Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total scores were used to generate standardized mean differences and 95% confidence intervals, which were combined in a random-effects model. Both mean percentage and absolute reduction in TWSTRS scores were calculated. Absolute reduction was used for forest plots.RESULTS: Eighteen studies met inclusion criteria, comprising 870 patients with 180 (21%) undergoing DBS and 690 (79%) undergoing peripheral denervation procedures. Mean follow-up was 31.5 months (range 12-38 months). In assessing efficacy of each intervention, forest plots revealed significant absolute reduction in total post-operative TWSTRS scores for both peripheral denervation (standardized mean difference 1.54; 95% CI 1.42-1.66) and DBS (standardized mean difference 2.07; 95% CI 1.43-2.71). On subgroup analysis, DBS therapy was significantly associated with improvement in post-operative TWSTRS severity (standardized mean difference 2.08; 95% CI 1.66-2.50) and disability (standardized mean difference 2.12; 95% CI 1.57-2.68), but not pain (standardized mean difference 1.18; 95% CI 0.80-1.55).CONCLUSIONS: Both peripheral denervation and DBS are associated with a significant reduction in absolute TWSTRS total score, with no significant difference in the magnitude of reduction observed between the two treatments. Further comparative data are needed to better evaluate the long-term results of both interventions.

View details for PubMedID 30419402

Abstract

INTRODUCTION: Sports surveillance databases provide valuable information regarding common ailments, yet fewer studies have focused on more rare peripheral nerve injuries. Our objective was to characterize peripheral nerve injuries in high school athletics with respect to incidence, time loss, mechanism, and diagnoses.METHODS: Sport-related nerve injury data on high school athletes were collected during the 2005/2006 through 2015/2016 academic years via the High School Reporting Information Online (RIO) database. All injuries were reported by certified athletic trainers (ATs). Descriptive statistics were performed.RESULTS: A total of 588 peripheral nerve injuries were recorded during the 2005/06-2015/16 academic years, with an overall incidence of 1.46/100,000 athlete-exposures (AE; 95%CI: 1.34, 1.58). Boys' football had the majority of injuries (71.3%) and the highest injury rate (5.46/100,000AE; 95%CI: 4.93, 5.98), followed by boys' wrestling (7.1%) and boys' baseball (3.4%). Over half (50.3%) of peripheral nerve injuries resulted in time loss <1 week, while 9.4% resulting in the athletes prematurely ending their seasons. The most common mechanisms were player contact (67.3%), overuse (10.0%), and surface contact (9.7%). A specific diagnosis was available for 40 (6.8%) injuries, including upper extremity stinger (n=26), spinal cord neurapraxia (n=3), subacromial nerve impingement (n=2) neuroma (n=2), axillary nerve palsy (n=1), sciatic nerve impingement (n=1), femoral nerve impingement (n=1), tarsal tunnel syndrome (n=1), peroneal neuropathy (n=1), thoracic outlet syndrome (n=1), and ulnar nerve subluxation (n=1).DISCUSSION: Recognized peripheral nerve injuries are rare among high school athletes, occurring most commonly in boys' football. While most are minor, approximately 1:10 were season-ending. Specific diagnoses were available for 7% of injuries, with upper extremity stingers being the most commonly reported diagnosis. Working with ATs to identify and implement methods to obtain more specific diagnostic information via surveillance will help researchers better understand the epidemiology of peripheral nerve injuries.

View details for PubMedID 30392428

Abstract

The objective of this study was to answer the typical questions from patients regarding the likely neurologic outcome and likelihood of recurrence when discussing peroneal intraneural ganglion cysts preoperatively.Retrospective analysis of all patients who underwent surgery for a peroneal intraneural ganglion cyst between January 1, 2000, and April 1, 2017, was performed. Postoperative neurologic outcomes and radiologic recurrences are reported.There were 65 patients. Average clinical follow-up was 14 months. Median dorsiflexion and eversion preoperatively were 2/5 and 4/5, respectively. Median dorsiflexion and eversion at last follow-up postoperatively were 5/5. Radiologic recurrence occurred in 6 (9%) patients, all extraneural.The data support excellent postoperative motor outcomes, despite frequent dense weakness of peroneal-innervated musculature preoperatively. The surgical approach appears to eliminate risk of intraneural recurrence and minimizes risk of extraneural recurrence. Muscle Nerve 57: 989-993, 2018.

View details for PubMedID 29315664

Abstract

Patients frequently have misconceptions regarding diagnosis, surgical indication, and expected outcome following spinal surgery for degenerative spinal disease. In this study, we sought to understand the relationship between patient-perceived surgical indications and patient expectations. We hypothesized that patients reporting appendicular symptoms as a primary surgical indication would report a higher rate of having expectations met by surgery compared to those patients reporting axial symptoms as a primary indication.Questionnaires were administered to patients who had undergone surgery for degenerative spinal disease at 2 tertiary care institutions. Questions assessed perception of the primary indication for undergoing surgery (radicular versus axial), whether the primary symptom improved after surgery, and whether patient expectations were met with surgery. Outcomes of interest included patient-reported symptomatic improvement following surgery and expectations met by surgery. Various factors were assessed for their relationship to these outcomes of interest.There were 151 unique survey respondents. Respondents were nearly split between having a patient-perceived indication for surgery as appendicular symptoms (55.6%) and axial symptoms (44.4%). Patient-perceived surgical indication being appendicular symptoms was the only factor predictive of patient-reported symptomatic improvement in our logistic regression model (OR 2.614; 95% CI 1.218-5.611). Patient-perceived surgical indication being appendicular symptoms (OR 3.300; 95% CI 1.575-6.944) and patient-reported symptomatic improvement (OR 33.297; 95% CI 12.186-90.979) were predictive of patients reporting their expectations met with surgery in both univariate and multivariate logistic regression modeling.We found that patient-reported appendicular symptoms as the primary indication for surgery were associated with a higher rate of both subjective improvement following surgery and having expectations met by surgery. Studies such as ours point to the fact that while performing technically superlative operations is paramount, it may be equally important to address other factors that help determine patient perception of the surgery experience.

View details for DOI 10.1016/j.clineuro.2017.03.007

View details for PubMedID 28359906

View details for DOI 10.1016/j.bjps.2017.05.022

View details for PubMedID 28579179

Abstract

The objective of this study was to review an historical cohort of patients with peroneal neuropathy and magnetic resonance imaging (MRI) read as negative for mass or cyst to determine if occult peroneal intraneural ganglion cysts can be identified on subsequent imaging review and to use this as an estimation of how under-recognized this pathologic entity is.The patient cohort utilized in this study was a previously published control cohort of 11 patients with peroneal neuropathy and MRI read as negative for mass or cyst. Clinical history, neurologic examination, and MRI studies of the knee were reviewed for each of the included patients. The primary outcome of interest was the presence of peroneal intraneural ganglion cyst on MRI.Overall, 7 of 11 (64%) patients in this historical "normal" cohort had evidence of a peroneal intraneural ganglion cyst on subsequent review of imaging. Deep peroneal-predominant weakness, knee pain, and tibialis anterior-predominant denervation/atrophy were seen more commonly in patients in whom an intraneural cyst was identified.This retrospective cohort study provides evidence that peroneal intraneural ganglion cysts are an historically under-recognized cause of peroneal neuropathy, with 64% of this historical "negative" cohort having evidence of a cyst on subsequent imaging review. Larger studies are needed to determine the treatment ramifications of identifying small cysts and to determine the clinical features suggestive of an intraneural ganglion cyst.

View details for DOI 10.1007/s00701-017-3130-3

View details for Web of Science ID 000399177300028

View details for PubMedID 28258311

Abstract

Neonatal brachial plexus palsy (NBPP) results in reduced function of the affected arm with profound ramifications on quality of life. Advances in surgical technique have shown improvements in outcomes for appropriately selected patients. Patient selection, however, remains difficult.To develop a decision algorithm that could be applied at the individual patient level, early in life, to reliably predict persistent NBPP that would benefit from surgery.Retrospective review of NBPP patients was undertaken. Maternal and neonatal factors were entered into the C5.0 statistical package in R (The R Foundation). A 60/40 model was employed, whereby 60% of randomized data were used to train the decision tree, while the remaining 40% were used to test the decision tree. The outcome of interest for the decision tree was a severe lesion meeting requirements for surgical candidacy.A decision tree prediction algorithm was generated from the entered variables. Variables utilized in the final decision tree included presence of Horner's syndrome, presence of a pseudomeningocele, Narakas grade, clavicle fracture at birth, birth weight >9 lbs, and induction or augmentation of labor. Sensitivity of the decision tree was 0.71, specificity 0.96, positive predictive value 0.94, negative predictive value 0.79, and F1 score 0.81.We developed a decision tree prediction algorithm that can be applied shortly after birth to determine surgical candidacy of patients with NBPP, the first of its kind utilizing only maternal and neonatal factors. This conservative decision tree can be used to offer early surgical intervention for appropriate candidates.

View details for DOI 10.1093/neuros/nyx190

View details for PubMedID 28419287

Abstract

Frontotemporal craniotomies are commonly performed for a variety of neurosurgical pathologies. Infections related to craniotomies cause significant morbidity. We hypothesized that the risk of cranial surgical site infections (SSIs) may be increased in patients whose frontal sinuses are breached during craniotomy.To compare the rate of cranial SSIs in patients undergoing frontotemporal craniotomies with and without frontal sinus breach (FSB).We performed a retrospective analysis of all patients undergoing frontotemporal craniotomies for the management of cerebral aneurysms from 2005 to 2014. This study included 862 patients undergoing 910 craniotomies. Primary outcome of interest was occurrence of a cranial SSI. Standard statistical methods were utilized to explore associations between a variety of variables including FSB, cranial SSI, and infections requiring reoperation.Of the 910 craniotomies, 141 (15.5%) involved FSB. Of those involving FSB, 22 (15.6%) developed a cranial SSI, compared to only 56 of the 769 without FSB (7.3%; P = .001). Cranial SSI requiring reoperation was much more likely in patients with FSB compared to those without a breach (7.8% vs 1.6%; P < .001). In those presenting with cranial SSIs, epidural abscess formation was more common with FSB compared to no FSB (27.3% vs 5.4%; P = .006). In multivariate analysis, breach of the frontal sinus was significantly associated with cranial SSI (OR 2.16; 95% CI 1.24-3.78; P = .01) and reoperation (OR 4.20; 95% CI 1.66-10.65; P = .003).Patients undergoing frontotemporal craniotomies are at significantly greater risk of serious cranial SSIs if the frontal sinus has been breached.

View details for DOI 10.1093/neuros/nyx046

View details for PubMedID 28327980

Abstract

When discussing the pathophysiology of ulnar neuropathy, Geoffrey Vaughan Osborne described a fibrous band that can be responsible for the symptoms seen in this disorder. In this paper, we take a glimpse at the life of Osborne and review the anatomy and surgical significance of Osborne's ligament. This band of tissue connects the two heads of the flexor carpi ulnaris and thus forms the roof of the cubital tunnel. To our knowledge, no prior publication has reviewed the history of this ligament, and very few authors have studied its anatomy in any detail. Therefore, the aim of the present paper is to elucidate this structure that is often implicated and surgically transected to decompress the ulnar nerve at the elbow.

View details for DOI 10.7759/cureus.1080

View details for PubMedID 28405530

View details for PubMedCentralID PMC5383373

View details for DOI 10.1002/ca.22863

View details for PubMedID 28247942

Abstract

Surgical transection of sensory nerves in the treatment of intractable neuropathic pain is a commonly performed procedure. At times these cases can be particularly challenging when encountering obese patients, when targeting deeper nerves or those with a variable branching pattern, or in the case of repeat operations. In this case series, the authors describe their experience with ultrasound-guided surgical instrument placement during transection of a saphenous nerve in the region of prior vascular surgery in 1 patient and in the lateral femoral cutaneous nerve in 2 obese patients. The authors also describe this novel technique and provide pilot data that suggests ultrasound-assisted surgery may allow for complex cases to be completed in an expedited fashion through smaller incisions.

View details for DOI 10.3171/2017.1.FOCUS16438

View details for Web of Science ID 000395837500006

View details for PubMedID 28245671

Abstract

OBJECTIVE The authors have observed that a subset of patients referred for evaluation of peroneal neuropathy with "negative" findings on MRI of the knee have subtle evidence of a peroneal intraneural ganglion cyst on subsequent closer inspection. The objective of this study was to introduce the nearly invisible peroneal intraneural ganglion cyst and provide illustrative cases. The authors further wanted to identify clues to the presence of a nearly invisible cyst. METHODS Illustrative cases demonstrating nearly invisible peroneal intraneural ganglion cysts were retrospectively reviewed and are presented. Case history and physical examination, imaging, and intraoperative findings were reviewed for each case. The outcomes of interest were the size and configuration of peroneal intraneural ganglion cysts over time, relative to various interventions that were performed, and in relation to physical examination and electrodiagnostic findings. RESULTS The authors present a series of cases that highlight the dynamic nature of peroneal intraneural ganglion cysts and introduce the nearly invisible cyst as a new and emerging part of the spectrum. The cases demonstrate changes in size and morphology over time of both the intraneural and extraneural compartments of these cysts. Despite "negative" MR imaging findings, nearly invisible cysts can be identified in a subset of patients. CONCLUSIONS The authors demonstrate here that peroneal intraneural ganglion cysts ride a roller coaster of change in both size and morphology over time, and they describe the nearly invisible cyst as one end of the spectrum. They identified clues to the presence of a nearly invisible cyst, including deep peroneal predominant symptoms, fluctuating symptoms, denervation changes in the tibialis anterior muscle, and abnormalities of the superior tibiofibular joint, and they correlate the subtle imaging findings to the internal fascicular topography of the common peroneal nerve. The description of the nearly invisible cyst may allow for increased recognition of this pathological entity that occurs with a spectrum of findings.

View details for DOI 10.3171/2016.12.FOCUS16439

View details for Web of Science ID 000395837500010

View details for PubMedID 28245669

Abstract

Repair of proximal hamstring avulsions requires mobilization of the sciatic nerve away from the tendon stump, which can be achieved with varying difficulty depending on the degree of scar formation and adherence. Predicting when a scarred, adherent, difficult-to-mobilize nerve will be encountered has been difficult.To identify clinical and/or radiological factors predictive of a difficult intraoperative dissection of the sciatic nerve during proximal hamstring repair.We retrospectively reviewed the medical records and preoperative magnetic resonance imaging of consecutive patients undergoing proximal hamstring repair. We compared the groups with and without a difficult sciatic nerve dissection.The total cohort consisted of 67 patients. Factors found to increase the likelihood of a difficult sciatic nerve dissection included complete conjoint tendon avulsion, higher maximal amount of tendon retraction, higher degree of imaging abnormality in the sciatic nerve, and higher degree of circumferential relationship of hematoma to the sciatic nerve. At a threshold of 23 for the Sciatic Nerve Dissection Score, the positive and negative predictive values were 53% and 88%, respectively. For the decision tree, the positive and negative predictive values were 75% and 87%, respectively.We have identified imaging factors associated with a scarred, adherent sciatic nerve that predict a difficult dissection during proximal hamstring repair. We have developed 2 novel methods-the Sciatic Nerve Dissection Score and a decision tree-that can be applied to predict the probability of a difficult sciatic nerve dissection at the time of surgical repair.

View details for PubMedID 29145673

Abstract

OBJECTIVE The use of nerve transfers versus nerve grafting for neonatal brachial plexus palsy (NBPP) remains controversial. In adult brachial plexus injury, transfer of an ulnar fascicle to the biceps branch of the musculocutaneous nerve (Oberlin transfer) is reportedly superior to nerve grafting for restoration of elbow flexion. In pediatric patients with NBPP, recovery of elbow flexion and forearm supination is an indicator of resolved NBPP. Currently, limited evidence exists of outcomes for flexion and supination when comparing nerve transfer and nerve grafting for NBPP. Therefore, the authors compared 1-year postoperative outcomes for infants with NBPP who underwent Oberlin transfer versus nerve grafting. METHODS This retrospective cohort study reviewed patients with NBPP who underwent Oberlin transfer (n = 19) and nerve grafting (n = 31) at a single institution between 2005 and 2015. A single surgeon conducted intraoperative exploration of the brachial plexus and determined the surgical nerve reconstruction strategy undertaken. Active range of motion was evaluated preoperatively and postoperatively at 1 year. RESULTS No significant difference between treatment groups was observed with respect to the mean change (pre- to postoperatively) in elbow flexion in adduction and abduction and biceps strength. The Oberlin transfer group gained significantly more supination (100 vs 19; p < 0.0001). Forearm pronation was maintained at 90 in the Oberlin transfer group whereas it was slightly improved in the grafting group (0 vs 32; p = 0.02). Shoulder, wrist, and hand functions were comparable between treatment groups. CONCLUSIONS The preliminary data from this study demonstrate that the Oberlin transfer confers an advantageous early recovery of forearm supination over grafting, with equivalent elbow flexion recovery. Further studies that monitor real-world arm usage will provide more insight into the most appropriate surgical strategy for NBPP.

View details for DOI 10.3171/2017.8.PEDS17160

View details for PubMedID 29219789

Abstract

Cervical dystonia, commonly referred to as spasmodic torticollis, is a neurological disorder characterized by aberrant, involuntary contraction of the muscles of the neck and shoulders. One surgical option that can be considered is selective cervical denervation.To report our modification of the Bertrand procedure for selective cervical denervation.Our modification of the Bertrand procedure for selective cervical denervation is reported with intraoperative photographs and schematic depictions of the operative steps.We report our modification of the Bertrand procedure for selective cervical denervation, which consists of a combination of C2-6 denervation, myectomy of the splenius capitis and/or semispinalis capitis, myotomy of the levator scapulae when indicated, and myotomy and selection denervation of the sternocleidomastoid. The combination of techniques utilized depends on the subtype and severity of cervical dystonia.Our modification of the original Bertrand procedure for selective cervical denervation represents an alternative surgical strategy for the treatment of cervical dystonia, with the potential advantages and disadvantages discussed.

View details for DOI 10.1093/ons/opx147

View details for PubMedID 29106650

Abstract

Muscle bellies of the hamstring muscles are intimately associated with the sciatic nerve, putting the sciatic nerve at risk of injury associated with proximal hamstring avulsion. There are few data informing the magnitude of this risk, identifying risk factors for neurologic injury, or determining neurologic outcomes in patients with distal sciatic symptoms after surgery.To characterize the frequency and nature of sciatic nerve injury and distal sciatic nerve-related symptoms after proximal hamstring avulsion and to characterize the influence of surgery on these symptoms.Cohort study; Level of evidence, 3.This was a retrospective review of patients with proximal partial or complete hamstring avulsion. The outcome of interest was neurologic symptoms referable to the sciatic nerve distribution below the knee. Neurologic symptoms in operative patients were compared pre- and postoperatively.The cohort consisted of 162 patients: 67 (41.4%) operative and 95 (58.6%) nonoperative. Sciatic nerve-related symptoms were present in 22 operative and 23 nonoperative patients, for a total of 45 (27.8%) patients (8 [4.9%] motor deficits, 11 [6.8%] sensory deficits, and 36 [22.2%] with neuropathic pain). Among the operative cohort, 3 of 3 (100.0%) patients showed improvement in their motor deficit postoperatively, 3 of 4 (75.0%) patients' sensory symptoms improved, and 17 of 19 (89.5%) patients had improvement in pain. A new or worsening deficit occurred in 5 (7.5%) patients postoperatively (2 [3.1%] motor deficits, 1 [1.5%] sensory deficit, and 3 [4.5%] with new pain). Predictors of operative intervention included lower age (odds ratio [OR], 0.952; 95% CI, 0.921-0.982; P = .001) and complete avulsion (OR, 10.292; 95% CI, 2.526-72.232; P < .001). Presence of neurologic deficit was not predictive.Sciatic nerve-related symptoms after proximal hamstring avulsion are underrecognized. Currently, neurologic symptoms are not considered when determining whether to pursue operative intervention. Given the high likelihood of improvement with surgical treatment, neurologic symptoms should be considered when making a decision regarding operative treatment.

View details for DOI 10.1177/2325967117713685

View details for PubMedID 28758137

View details for PubMedCentralID PMC5513525

Abstract

The authors present a case of delayed peroneal neuropathy following a lateral gastrocnemius rotational flap reconstruction. The patient presented 1.5 years after surgery with a new partial foot drop, which progressed over 3 years. At operation, a fascial band on the deep side of the gastrocnemius flap was compressing the common peroneal nerve proximal to the fibular head, correlating with preoperative imaging. Release of this fascial band and selective muscle resection led to immediate improvement in symptoms postoperatively.

View details for DOI 10.3171/2017.2.JNS162711

View details for PubMedID 28753118

Abstract

Offering real-time, high-resolution images via intraoperative ultrasound is advantageous for a variety of peripheral nerve applications. To highlight the advantages of ultrasound, its extraoperative uses are reviewed. The current intraoperative uses, including nerve localization, real-time evaluation of peripheral nerve tumors, and implantation of leads for peripheral nerve stimulation, are reviewed. Although intraoperative peripheral nerve localization has been performed previously using guide wires and surgical dyes, the authors' approach using ultrasound-guided instrument clamps helps guide surgical dissection to the target nerve, which could lead to more timely operations and shorter incisions.

View details for DOI 10.1016/j.nec.2017.05.013

View details for PubMedID 28917290

Abstract

OBJECTIVE The authors hypothesized that when the anatomical variant of an anconeus epitrochlearis is present, the risk of developing cubital tunnel syndrome would be reduced by replacing the normal roof of the cubital tunnel (Osborne's ligament) with a more forgiving muscular structure, the anconeus epitrochlearis. The authors further hypothesized that when the presence of an anconeus epitrochlearis contributes to ulnar neuropathy, it would be secondary to muscular hypertrophy, thereby making it more likely to occur in the dominant arm. Therefore, the goal of the present study was to evaluate these hypotheses. METHODS This retrospective cohort study was performed by reviewing the records of all adult patients who underwent operative intervention for cubital tunnel syndrome between 2005 and 2014 as the experimental group and all asymptomatic patients in the medical literature who were part of a series reporting the prevalence of an anconeus epitrochlearis as the control group. The primary outcome of interest was the presence of an anconeus epitrochlearis in asymptomatic individuals versus patients with cubital tunnel syndrome. RESULTS During the study period, 168 patients underwent decompression of the ulnar nerve for cubital tunnel syndrome, and an anconeus epitrochlearis was found at surgery in 9 (5.4%) patients. The control group consisted of 634 asymptomatic patients from the medical literature, and an anconeus epitrochlearis was present in 98 (15.5%) of these patients. An anconeus epitrochlearis was present significantly less frequently in the symptomatic patients than in asymptomatic individuals (p < 0.001). Among patients undergoing surgical decompression, an anconeus epitrochlearis was associated with symptoms in the dominant arm (p = 0.037). CONCLUSIONS The authors found that an anconeus epitrochlearis was present significantly less often in patients with cubital tunnel syndrome than in asymptomatic controls. The mechanism of protection may be that this muscle decreases the rigidity of the entrance into the cubital tunnel. When an anconeus epitrochlearis does contribute to cubital tunnel syndrome, it is significantly more likely to occur in the dominant arm, possibly due to repetitive use and hypertrophy of the anconeus epitrochlearis. The presence of an anconeus epitrochlearis may be protective against the development of cubital tunnel syndrome, although this is a preliminary finding.

View details for DOI 10.3171/2015.10.JNS151668

View details for Web of Science ID 000388783000024

View details for PubMedID 26871208

Abstract

Glioma cells grow in two phenotypic forms, as adherent monolayers and as free floating "neurospheres/tumorspheres", using specific media supplements. Whether each phenotype is irreversible remains unknown. Herein we show that both states are reversible using patient derived glioblastoma cell cultures (i.e., HF2303, IN859, MGG8, IN2045). Both phenotypic states differ in proliferation rate, invasion, migration, chemotaxis and chemosensitivity. We used microarrays to characterize gene expression across the patient derived glioblastoma cell cultures, to find specific inhibitors of the sphere population. Traditional chemotherapeutics (i.e., doxorubicin or paclitaxel) inhibit rapidly dividing adherent cells; it has been more challenging to inhibit the growth of the sphere phenotype. PRKG1, known to induce apoptosis when activated, is increased in all patient derived glioblastoma spheres. Stimulation of PRKG1 activity preferentially reduced cell viability in the sphere phenotype. Computational network and gene ontology analysis identified novel potential target genes linked to the PRKG1 expression node.

View details for DOI 10.18632/oncotarget.11589

View details for Web of Science ID 000387167800017

View details for PubMedID 27564115

View details for PubMedCentralID PMC5325344

Abstract

Airway pressure release ventilation (APRV) utilizes high levels of airway pressure coupled with brief expiratory release to facilitate open lung ventilation. The aim of our study was to evaluate the effects of APRV-induced elevated airway pressure mean in patients with severe traumatic brain injury.This was a retrospective cohort study at a 424-bed Level I trauma center. Linear mixed effects models were developed to assess the difference in therapeutic intensity level (TIL), intracranial pressure (ICP), and cerebral perfusion pressure (CPP) over time following the application of APRV.The study included 21 epochs of APRV in 21 patients. In the 6-hour epoch following the application of APRV, the TIL was significantly increased (P = .002) and the ICP significantly decreased (P = .041) compared to that before 6 hours. There was no significant change in CPP (P = .42) over time. The baseline static compliance and time interaction was not significant for TIL (2 = 0.2 [df 1], P = .655), CPP (2 = 0 [df 1], P = 1), or ICP (2 = 0.1 [df 1], P = .752).Application of APRV in patients with severe traumatic brain injury was associated with significantly, but not clinically meaningful, increased TIL and decreased ICP. No significant change in CPP was observed. No difference was observed based on the baseline pulmonary static compliance.

View details for PubMedID 27651443

Abstract

OBJECTIVE Our understanding of pediatric cervical spine development remains incomplete. The purpose of this analysis was to quantitatively define cervical spine growth in a population of children with normal CT scans. METHODS A total of 1458 children older than 1 year and younger than 18 years of age who had undergone a cervical spine CT scan at the authors' institution were identified. Subjects were separated by sex and age (in years) into 34 groups. Following this assignment, subjects within each group were randomly selected for inclusion until a target of 15 subjects in each group had been measured. Linear measurements were performed on the midsagittal image of the cervical spine. Twenty-three unique measurements were obtained for each subject. RESULTS Data showed that normal vertical growth of the pediatric cervical spine continues up to 18 years of age in boys and 14 years of age in girls. Approximately 75% of the vertical growth occurs throughout the subaxial spine and 25% occurs across the craniovertebral region. The C-2 body is the largest single-segment contributor to vertical growth, but the subaxial vertebral bodies and disc spaces also contribute. Overall vertical growth of the cervical spine throughout childhood is dependent on individual vertebral body growth as well as vertical growth of the disc spaces. The majority of spinal canal diameter growth occurs by 4 years of age. CONCLUSIONS The authors' morphometric analyses establish parameters for normal pediatric cervical spine growth up to 18 years of age. These data should be considered when evaluating children for potential surgical intervention and provide a basis of comparison for studies investigating the effects of cervical spine instrumentation and fusion on subsequent growth.

View details for DOI 10.3171/2016.3.PEDS1612

View details for Web of Science ID 000381781300017

View details for PubMedID 27231821

Abstract

OBJECTIVE The aim of this paper is to compare the accuracy of the freehand technique versus the use of intraoperative guidance (either ultrasound guidance or frameless stereotaxy) for placement of parietooccipital ventricular catheters and to determine factors associated with reduced proximal shunt failure. METHODS This retrospective cohort study included all patients from 2 institutions who underwent a ventricular cerebrospinal fluid (CSF) shunting procedure in which a new parietooccipital ventricular catheter was placed between January 2005 and December 2013. Data abstracted for each patient included age, sex, method of ventricular catheter placement, side of ventricular catheter placement, Evans ratio, and bifrontal ventricular span. Postoperative radiographic studies were reviewed for accuracy of ventricular catheter placement. Medical records were also reviewed for evidence of shunt failure requiring revision. Standard statistical methods were used for analysis. RESULTS A total of 257 patients were included in the study: 134 from the University of Michigan and 123 from Washington University in St. Louis. Accurate ventricular catheter placement was achieved in 81.2% of cases in which intraoperative guidance was used versus 67.3% when the freehand technique was used. Increasing age reduced the likelihood of accurate catheter placement (OR 0.983, 95% CI 0.971-0.995; p = 0.005), while the use of intraoperative guidance significantly increased the likelihood (OR 2.809, 95% CI 1.406-5.618; p = 0.016). During the study period, 108 patients (42.0%) experienced shunt failure, 79 patients (30.7%) had failure involving the proximal catheter, and 53 patients (20.6%) had distal failure (valve or distal catheter). Increasing age reduced the likelihood of being free from proximal shunt failure (OR 0.983, 95% CI 0.970-0.995; p = 0.008), while both the use of intraoperative guidance (OR 2.385, 95% CI 1.227-5.032; p = 0.011), and accurate ventricular catheter placement (OR 3.424, 95% CI 1.796-6.524; p = 0.009) increased the likelihood. CONCLUSIONS The use of intraoperative guidance during parietooccipital ventricular catheter placement as part of a CSF shunt system significantly increases the likelihood of accurate catheter placement and subsequently reduces the rate of proximal shunt failure.

View details for DOI 10.3171/2016.5.FOCUS16159

View details for Web of Science ID 000383442500010

View details for PubMedID 27581306

Abstract

Despite recent improvements in perinatal care, the incidence of neonatal brachial plexus palsy (NBPP) remains relatively common. CT myelography is currently considered to be the optimal imaging modality for evaluating nerve root integrity. Recent improvements in MRI techniques have made it an attractive alternative to evaluate nerve root avulsions (preganglionic injuries).We demonstrate the utility of MRI for the evaluation of normal and avulsed spinal nerve roots. We also show the utility of ultrasound in providing useful preoperative evaluation of the postganglionic brachial plexus in patients with NBPP.

View details for DOI 10.1007/s00381-016-3106-2

View details for Web of Science ID 000380667400010

View details for PubMedID 27179536

Abstract

Observational studies suggest peripherally inserted central venous catheters (PICCs) are associated with a high risk of catheter-related large vein thrombosis (CRLVT) in critically ill neurologic patients. We evaluated the difference in thrombosis risk between PICCs and centrally inserted central venous catheters (CICVCs).We conducted a pragmatic, randomized controlled trial of critically ill adult neurologic patients admitted to neurological and trauma critical care units at two level I trauma centers. Patients were randomized to receive either a PICC or CICVC and undergo active surveillance for CRLVT or death within 15days of catheter placement.In total, 39 subjects received a PICC and 41 received a CICVC between February 2012 and July 2015. The trial was stopped after enrollment of 80 subjects due to feasibility affected by slow enrollment and funding. In the primary intention-to-treat analysis, 17 (43.6%) subjects that received a PICC compared to 9 (22.0%) that received a CICVC experienced the composite of CRLVT or death, with a risk difference of 21.6% (95% CI 1.57-41.71%). Adjusted common odds ratio of CRLVT/death was significantly higher among subjects randomized to receive a PICC (adjusted OR 3.08; 95% CI 1.1-8.65). The higher adjusted odds ratio was driven by risk of CRLVT, which was higher in those randomized to PICC compared to CICVC (adjusted OR 4.66; 95% CI 1.3-16.76) due to increased large vein thrombosis without a reduction in proximal deep venous thrombosis.Our trial demonstrates that critically ill neurologic patients who require a central venous catheter have significantly lower odds of ultrasound-diagnosed CRLVT with placement of a CICVC as compared to a PICC.

View details for DOI 10.1007/s12028-016-0247-9

View details for Web of Science ID 000380150700004

View details for PubMedID 26842716

Abstract

Patients with an unruptured intracranial aneurysm treated with coil embolization are routinely admitted to the intensive care unit (ICU) after the procedure; however, this practice is questionable. The purpose of this study was to determine if routine admission to the ICU is necessary for patients undergoing coil embolization of an unruptured intracranial aneurysm.We conducted a retrospective cohort study of all patients undergoing elective endovascular treatment of an unruptured intracranial aneurysm between 2005 and 2012 at our institution. Multivariate regression analysis was performed to identify predictors of outcome. Cost savings analysis compared ICU admission to step-down or telemetry unit admission.311 unruptured intracranial aneurysms were treated by coil embolization (190), balloon remodeling (13), or stent-assisted coiling (108). Eleven (3.5%) neurologic complications were noted; 5 (1.6%) of these were permanent. Multivariate regression analysis identified female sex (p=0.028), hypercoagulability (p=0.021), aneurysm size >2cm (p=0.003), and intraoperative rupture (p<0.001) as predictors of a post-procedural neurologic complication. Cost savings were 57% for admission to a step-down unit and 32% for admission to a telemetry unit compared with ICU admission.Neurologic complications are rare in the treatment of unruptured intracranial aneurysms, suggesting that routine ICU admission after treatment may not be necessary. Female sex, history of hypercoagulability, aneurysm size >2cm, and an intraprocedural rupture were predictive of a postoperative complication. ICU monitoring in these subgroups may therefore be warranted.

View details for DOI 10.1136/neurintsurg-2016-012511

View details for PubMedID 27382122

Abstract

ObjectiveThe factors associated with persistent neonatal brachial plexus palsy (PNBPP) are unknown. Our objectives are to compare PNBPP at 1 and 2 years in children delivered via vaginal delivery (VD) versus cesarean delivery (CD) and in children delivered via VD with or without reported shoulder dystocia (SD). Study DesignRetrospective cohort of children diagnosed with neonatal brachial plexus palsy (NBPP). Maternally reported delivery history and presence of SD were recorded with Student t-test, chi-square test, and odds ratio (OR) with 95% confidence intervals (CI) calculated for comparisons. ResultsOf 387 cases of NBPP, 8% (30) delivered via CD. Rates of PNBPP were higher in the VD group at 1 and 2 years (60% of CD and 85% of VD; OR, 0.26; 95% CI, 0.11-0.62 at 1year; 33% of CD and 73% of VD; OR, 0.15; 95% CI, 0.05-0.39 at 2 years). There was no difference in PNBPP in women with VD with or without maternally reported SD (87 vs. 85%, p=0.68 at 1year; 64 vs. 61%, p=0.61 at 2 years). ConclusionPNBPP is possible with CD, and there is no difference in PNBPP in VD with or without maternally reported SD. A prospective study is warranted to ascertain associative factors.

View details for DOI 10.1055/s-0036-1571351

View details for PubMedID 26890435

Abstract

A motorcyclist sustained multiple-system trauma, including a left buttock hematoma requiring decompression and evacuation. Presentation for severe hip pain and lower extremity weakness was delayed. Imaging revealed myositis ossificans traumatica compressing the sciatic nerve in the buttock. The patient underwent sciatic nerve decompression with resection of heterotopic calcification, resulting in improvement in pain and left lower extremity function. This case illustrates the contrast in differential diagnosis of peripheral nerve injury immediately posttrauma and that occurring in a slow, delayed fashion posttrauma. Myositis ossificans may be an underrecognized complication of trauma but should be considered in cases of delayed peripheral nerve injury after trauma.

View details for DOI 10.1016/j.pmrj.2015.10.011

View details for Web of Science ID 000375749500011

View details for PubMedID 26548968

Abstract

Sonography is now considered an effective method to evaluate peripheral nerves. Low cost, high resolution, the ability to image an entire limb in a short time, and dynamic assessment are several of the positive attributes of sonography. This article will review the normal appearance of peripheral nerves as shown with sonography. In addition, the most common applications for sonography of the peripheral nerves will be reviewed, which include entrapment neuropathies, intraneural ganglion cyst, nerve trauma, and peripheral nerve sheath tumors. Clinical information related to nerve disorders is also included, as it provides valuable information that can be obtained during sonographic examinations, increasing diagnostic accuracy.

View details for DOI 10.7863/ultra.15.05061

View details for Web of Science ID 000375333200002

View details for PubMedID 26931790

Abstract

Patients presenting with enlarging fibrofatty masses in the extremities pose an interesting dilemma to clinicians, as the differential diagnosis in such cases ranges from benign to malignant, and from lesions optimally managed operatively to those managed nonoperatively. The differential diagnosis includes benign lipoma, liposarcoma, lipoblastoma, and fibrolipomatous hamartoma (lipomatosis) of the nerves. The authors present the case of a 14-year-old girl with an enlarging fibrofatty mass of the forearm, initially thought, based on diagnostic imaging, to be a fibrolipomatous hamartoma of the median nerve, but found to be a lipoblastoma without direct nerve involvement based on histopathological examination of the operative specimen. This case serves to illustrate the diagnostic predicament that can exist with such masses. The authors advocate the need to establish a tissue diagnosis while having a contingency plan for each of the diagnostic possibilities because the management of each lesion is markedly different. In this report, the authors consider the differential diagnosis of fibrofatty masses of the extremities that the peripheral nerve surgeon may encounter, and they highlight the significant differences in management strategies for each possible diagnosis.

View details for DOI 10.3171/2015.2.PEDS14570

View details for Web of Science ID 000367027900011

View details for PubMedID 26451716

Abstract

The aim of the current study is to describe the complication rates and clinical outcomes in patients who either underwent repeat intervention or conservative management with radiographic surveillance when presenting with aneurysmal recurrence after endovascular treatment. Since publication of the international subarachnoid aneurysm trial (ISAT), an increasing number of patients are treated with endovascular therapy. However, recurrence after endovascular therapy continues to pose a challenge, and there is minimal evidence to guide its management. We performed a retrospective review of all patients who underwent endovascular treatment of an intracranial aneurysm from January 2005 to February 2013. The patients who had an aneurysmal recurrence following the initial endovascular treatment were identified and divided into two groups: those followed with conservative management (n=24), and those who underwent reintervention (n=65). The groups were compared for complications and clinical outcomes. When a reintervention was undertaken, microsurgical clip ligation was associated with a higher rate of occlusion than additional endovascular therapy (p<0.001). When comparing conservative treatment and reintervention, there was no statistically significant difference in complications or clinical outcomes. Reintervention was more common in patients who were younger, had presented with subarachnoid hemorrhage, or had a greater degree of recurrence. We conclude that clinical outcomes and repeat subarachnoid hemorrhage are similar in patients who underwent retreatment versus those who had conservative management for their recurrent cerebral aneurysms.

View details for DOI 10.1016/j.jocn.2015.04.012

View details for Web of Science ID 000365370600010

View details for PubMedID 26256068

Abstract

Intraoperative angiography (IOA) is essential in evaluating residual aneurysm following clip ligation, but it does lead to an additional procedure which increases the duration of the procedure as well as increasing room traffic. We examined whether IOA during microsurgery is a risk factor for developing cranial surgical site infection.A retrospective cohort study was performed of all patients undergoing craniotomy for aneurysm treatment between 2005 and 2012 at the University of Michigan. IOA was used at the surgeons' discretion. The primary outcome of interest was occurrence of a surgical site infection and the secondary outcome of interest was clip repositioning following IOA. Variables including IOA were tested for their independent association with the occurrence of a surgical site infection.During the study period 676 intracranial aneurysms were treated by craniotomy; IOA was used in 104 of these cases. There were a total of 20 surgical site infections, 2 in the IOA group (1.9%) and 18 in the non-IOA group (3.1%), indicating that IOA was not a statistically significant variable for infection (p=0.50). No additional single variable measured could be shown to have a statistically significant increase in infection, and there were no direct complications related to the use of IOA (stroke, dissection, perforation).IOA does not increase the risk of developing a surgical site infection. It can be conducted without exposing patients to an undue risk of infection.

View details for DOI 10.1136/neurintsurg-2014-011346

View details for Web of Science ID 000361756100013

View details for PubMedID 25155479

Abstract

High-volume centers have better outcomes than low-volume centers when managing complex conditions including subarachnoid hemorrhage (SAH).To quantify SAH volume-outcome association and determine the extent to which this association is influenced by aggressiveness of care.A serial cross-sectional retrospective study using the Nationwide Inpatient Sample for 2002 to 2010 was performed. Included were all adult (older than 18 years of age) discharged patients with a primary diagnosis of SAH admitted from the emergency department or transferred to a discharging hospital; cases of trauma or arteriovenous malformation were excluded. Survey-weighted descriptive statistics estimated temporal trends. Multilevel logistic regression estimated volume-outcome associations for inpatient mortality and discharge home. Models were adjusted for demographic characteristics, year, transfer status, insurance status, all individual Charlson comorbidities, intubation, and all patient-refined, diagnosis-related group mortality. Analyses were repeated, excluding cases in which aggressive care was not pursued.A total of 32,336 discharges were included; 13,398 patients underwent clipping (59.1%) or coiling (40.9%). The inpatient mortality rate decreased from 32.2% in 2002 to 22.2% in 2010; discharge home increased from 28.5% to 40.8% during the same period. As SAH volume decreased from 100/year, the mortality rate increased from 18.7% to 19.8% at 80/year, 21.7% at 60/year, 24.5% at 40/year, and 28.4% at 20/year. As SAH patient volume decreased, the probability of discharge home decreased from 40.3% at 100/year to 38.7% at 60/year, and 35.3% at 20/year. Better outcomes persisted in patients receiving aggressive care and in those not receiving aggressive care.Short-term SAH outcomes have improved. High-volume hospitals have more favorable outcomes than low-volume hospitals. This effect is substantial, even for hospitals conventionally classified as high volume.

View details for DOI 10.1227/NEU.0000000000000850

View details for Web of Science ID 000359680700032

View details for PubMedID 26110818

View details for PubMedCentralID PMC4869982

Abstract

Endovascular treatment of small intracranial aneurysms has historically been technically challenging and has been associated with high rates of complications and intraprocedural rupture. In this study, we compared complication and recurrence rates for treatment of small aneurysms ( 4 mm) versus large aneurysms in the context of the advent of improvements in endovascular techniques and technologies.A retrospective cohort study was performed to include all patients who underwent coiling of an intracranial aneurysm between 2005 and 2012. Small aneurysms were defined as any aneurysm 4.0 mm or smaller in all dimensions. The primary outcome was a composite outcome of the occurrence of an intraoperative rupture or a perioperative thromboembolic event. The secondary outcome of interest was aneurysm recurrence.During the study period, 483 patients were treated using endovascular techniques; 85 (17.6%) of these patients had small aneurysms. In the small aneurysm group, there was only one (1.2%) intraoperative rupture, three (3.5%) perioperative thromboembolic events, and 11 (12.9%) incidents of aneurysm recurrence. Both the primary and secondary outcomes of interest were similar in patients presenting with small or large aneurysms. Small aneurysm size was not a risk factor for either the composite primary outcome or aneurysm recurrence in multivariate analysis.Treatment of small intracranial aneurysms via conventional endovascular coiling techniques is not inferior to endovascular treatment of larger aneurysms based on our single institution experience. While technically challenging, such aneurysms may be treated safely and effectively with acceptable rates of complications and recurrence.

View details for DOI 10.1136/neurintsurg-2014-011133

View details for Web of Science ID 000351619400012

View details for PubMedID 24623836

Abstract

We hypothesized that the subset of patients with early hydrocephalus following aneurysmal subarachnoid hemorrhage may represent a subset of patients with a more vehement inflammatory reaction to blood products in the subarachnoid space. We thus examined risk factors for early hydrocephalus and examined the relationship between early hydrocephalus and symptomatic vasospasm as well as clinical outcome.We retrospectively analyzed all patients presenting to our institution with subarachnoid hemorrhage over a 7-year period. We examined for risk factors, including early hydrocephalus, for poor clinical outcome and symptomatic vasospasm.We found intraventricular hemorrhage to be strongly associated with the development of early hydrocephalus. In univariate analysis, early hydrocephalus was strongly associated with both poor functional outcome and symptomatic vasospasm. In multivariate analysis, intraventricular hemorrhage and tobacco use were associated with symptomatic vasospasm; intraventricular hemorrhage, intraparenchymal hemorrhage, and symptomatic vasospasm were associated with poor functional outcome.We found that intraventricular hemorrhage was strongly associated with early hydrocephalus. Further exploration of the mechanistic explanation is needed, but we suggest this may be from a combination of obstruction of cerebrospinal fluid pathways by blood products and inflammation in the choroid plexus resulting in increased cerebrospinal fluid production. Further, we suggest that both early hydrocephalus and cerebral vasospasm may be parts of the overall inflammatory cascade that occurs with intraventricular hemorrhage and ultimately results in a poorer clinical outcome.

View details for DOI 10.1055/s-0034-1394189

View details for Web of Science ID 000350742400006

View details for PubMedID 25545809

Abstract

The objective of our study was to examine patients with aneurysmal subarachnoid hemorrhage transferred and directly admitted to our institution in order to determine how transfer time affects outcomes.A retrospective cohort study was performed of all patients undergoing treatment for aneurysmal subarachnoid hemorrhage between 2005 and 2012 at the University of Michigan. Variables, including transfer time, were tested for their independent association with the primary outcomes of symptomatic vasospasm and 12-month outcome as well as secondary outcomes of aneurysm rebleeding and 12-month mortality.During the study period, 263 (87.4%) patients were transferred to our institution and 38 (12.6%) were directly admitted for treatment of aneurysmal subarachnoid hemorrhage. Transfer time was not associated with the occurrence of symptomatic vasospasm, 12-month outcome, rebleeding, or 12-month mortality. Higher Hunt-Hess grade was associated with the occurrence of symptomatic vasospasm as well as with poorer 12-month outcome.Transfer time was not associated with the occurrence of symptomatic vasospasm, 12-month outcome, rebleeding, or 12-month mortality. We believe our data argue that protocols should emphasize early resuscitation and stabilization followed by safe transfer rather than a hyperacute transfer paradigm. However, transfer time should be minimized as much as possible so as not to delay time to definitive treatment.

View details for DOI 10.1016/j.jstrokecerebrovasdis.2014.09.009

View details for Web of Science ID 000349177300025

View details for PubMedID 25497722

Abstract

As medical costs continue to rise during a time of increasing medical resource utilization, both hospitals and physicians must attempt to limit superfluous health care expenses. Neurointerventional treatment has been shown to be costly, but it is often the best treatment available for certain neuropathologies. The authors studied the effects of 3 policy changes designed to limit the costs of performing neurointerventional procedures at the University of Michigan.The authors retrospectively analyzed the costs of performing neurointerventional procedures during the 6-month periods before and after the implementation of 3 cost-saving policies: 1) the use of an alternative, more economical contrast agent, 2) standardization of coil prices through negotiation with industry representatives to receive economies of scale, and 3) institution of a feedback method to show practitioners the costs of unused products per patient procedure. The costs during the 6-month time intervals before and after implementation were also compared with costs during the most recent 6-month time period.The policy requiring use of a more economical contrast agent led to a decrease in the cost of contrast usage of $42.79 per procedure for the first 6 months after implementation, and $137.09 per procedure for the most current 6-month period, resulting in an estimated total savings of $62,924.31 for the most recent 6-month period. The standardized coil pricing system led to savings of $159.21 per coil after the policy change, and $188.07 per coil in the most recent 6-month period. This yielded total estimated savings of $76,732.56 during the most recent 6-month period. The feedback system for unused items decreased the cost of wasted products by approximately $44.36 per procedure in the 6 months directly after the policy change and by $48.20 per procedure in the most recent 6-month period, leading to total estimated savings of $22,123.80 during the most recent 6-month period. According to extrapolation over a 1-year period, the 3 policy changes decreased costs by an estimated $323,561.34.Simple cost-saving policies can lead to substantial reductions in costs of neurointerventional procedures while maintaining high levels of quality and growth of services.

View details for DOI 10.3171/2014.7.JNS14236

View details for Web of Science ID 000343530400011

View details for PubMedID 25170667

Abstract

Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults and it carries a dismal prognosis. Adenoviral vector (Ad)-mediated gene transfer is being developed as a promising therapeutic strategy for GBM. Preclinical studies have demonstrated safety and efficacy of adenovirus administration into the brain and tumor mass in rodents and into the non-human primates' brain. Importantly, Ads have been safely administered within the tumor resection cavity in humans.This review gives background on GBM and Ads; we describe gene therapy strategies for GBM and discuss the value of combination approaches. Finally, we discuss the results of the human clinical trials for GBM that have used Ads.The transduction characteristics of Ads, and their safety profile, added to their capacity to achieve high levels of transgene expression have made them powerful vectors for the treatment of GBM. Recent gene therapy successes in the treatment of retinal diseases and systemic brain metabolic diseases encourage the development of gene therapy for malignant glioma. Exciting clinical trials are currently recruiting patients; although, it is the large randomized Phase III controlled clinical trials that will provide the final decision on the success of gene therapy for the treatment of GBM.

View details for DOI 10.1517/14712598.2014.915307

View details for Web of Science ID 000340460000004

View details for PubMedID 24773178

View details for PubMedCentralID PMC4127140

Abstract

Spontaneous intracranial hypotension can be a therapeutic challenge to the treating physician. In this study, we present our experience with the administration of a large-volume blood patch to multiple sites in the epidural space through a single-catheter access site.A retrospective review was conducted of patients with spontaneous intracranial hypotension who underwent a large-volume blood patch to multiple sites in the epidural space through a single-catheter access site from 2010 to 2012. Patient demographic data, clinical charts, indications for treatment, radiographic images, procedure notes, and postprocedure hospital course were reviewed.Overall, 9 patients were identified who underwent 20 blood patch procedures. Patients were selected to undergo the large-volume procedure either because they had a failed site-directed epidural blood patch or if imaging demonstrated multiple possible leak sites. There were 6 women and 3 men, with an average age of 33.5 years. The mean volume of blood injected per procedure was 54.1 mL (median=55 mL; range=38-70 mL). All patients had an orthostatic headache as one of their presenting symptoms; 22% also presented with neurocognitive decline and behavioral changes; 89% of patients had improvement or resolution of their symptoms; and 80% of patients who had a previously failed site-directed epidural blood or fibrin glue patch improved with a large volume catheter-directed blood patch.Our experience supports the use of a large-volume blood patch to multiple sites in the epidural space through a single-catheter access site for the treatment of spontaneous intracranial hypotension. Additionally, our results indicate a role for this procedure in refractory cases of spontaneous intracranial hypotension.

View details for DOI 10.3174/ajnr.A3945

View details for Web of Science ID 000341639900032

View details for PubMedID 24788127

Abstract

Mannitol has been shown to damage endothelial cells and activate coagulation pathways leading to intravascular thrombosis. Dehydration and hemagglutination have also been associated with mannitol use, although the risk of clinically evident venous thromboembolism (VTE) disease is not well-defined. The aim of this study was to compare the risk of VTE in critically ill neurological patients who received mannitol compared to only hypertonic saline. A case-cohort study design with propensity score matching was used to evaluate the risk of VTE among patients who received mannitol compared to those who received hypertonic saline alone. The odds of thrombosis were evaluated by the Cochran-Mantel-Haenszel method and conditional logistic regression was used to adjust for year of treatment. Ninety-one of 330 patients (27.6%; 95% confidence interval [CI] 23-33%) developed a VTE; however, the yearly proportion remained unchanged over the 8 year study period. Cumulative use of mannitol declined and use of hypertonic saline increased significantly. The odds of thrombosis for those exposed to mannitol compared to hypertonic saline alone was 1.11 (95% CI 0.65-1.73; p=0.75). This remained insignificant after adjusting for year of injury. In conclusion, despite a significant change in the pattern of osmotic therapy used at our institution, the proportion of patients with VTE remained unchanged. We found no evidence that mannitol use was associated with VTE compared to hypertonic saline alone.

View details for DOI 10.1016/j.jocn.2013.12.013

View details for Web of Science ID 000339601400010

View details for PubMedID 24685012

Abstract

Filum terminale lipomas (FTLs) are being identified with increasing frequency due to the increasing utilization of MRI. Although an FTL may be associated with tethered cord syndrome (TCS), in many cases FTLs are diagnosed incidentally in patients without any symptoms of TCS. The natural history of FTLs is not well defined.The authors searched the clinical and imaging records at a single institution over a 14-year interval to identify patients with FTLs. For patients with an FTL, the clinical records were reviewed for indication for imaging, presenting symptoms, perceived need for surgery, and clinical outcome. A natural history analysis was performed using all patients with more than 6 months of clinical follow-up.A total of 436 patients with FTL were identified. There were 217 males and 219 females. Of these patients, 282 (65%) were adults and 154 (35%) were children. Symptoms of TCS were present in 22 patients (5%). Fifty-two patients underwent surgery for FTL (12%). Sixty-four patients (15%) had a low-lying conus and 21 (5%) had a syrinx. The natural history analysis included 249 patients with a mean follow-up time of 3.5 years. In the follow-up period, only 1 patient developed new symptoms.Filum terminale lipomas are a common incidental finding on spinal MRI, and most patients present without associated symptoms. The untreated natural history is generally benign for asymptomatic patients.

View details for DOI 10.3171/2014.2.PEDS13528

View details for Web of Science ID 000334903700013

View details for PubMedID 24628511

Abstract

Thromboembolic events represent a clinically significant cause of neurological morbidity during the endovascular management of cerebral aneurysms. We have implemented an anti-thromboembolic regimen consisting of pre- and postoperative dual antiplatelet therapy, as well as postoperative anticoagulation using heparin and dextran. The aims of our study were to examine the effect of this regimen on thromboembolic rates during elective aneurysm coiling, and to elucidate risk factors associated with the development of thromboembolic events in this setting.We conducted a retrospective review of patients who underwent elective intracranial aneurysm coiling between January 2005 and February 2012. The primary outcome of interest was the occurrence of a clinically significant peri-procedural thromboembolic event. Secondary outcomes included the occurrence of a central nervous system (CNS) or systemic hemorrhage.During the study period, 312 patients underwent elective aneurysm coiling and six (2%) thromboembolic events occurred; three (1%) occurred in the group that received the anti-thromboembolic regimen (261 patients) and three (6%) occurred in the group that did not receive the regimen (51 patients), resulting in a statistically significant difference (P=0.024). Both the presence of a hypercoagulable state (P=0.014) and the lack of the anti-thromboembolic regimen (P=0.043) were significantly associated with the occurrence of a thromboembolic event.This study provides evidence that the regimen described here is safe and reduces thromboembolic complications during elective aneurysm coiling. Ours is likely the most aggressive regimen in the published literature and significantly reduced the rate of thromboembolism without any significant increase hemorrhagic complications.

View details for DOI 10.1007/s00701-014-2031-y

View details for Web of Science ID 000334426000004

View details for PubMedID 24595538

Abstract

Use of an external ventricular drain (EVD) is essential for managing patients with hydrocephalus or intracranial hypertension. While this procedure is safe and efficacious, ventriculostomy-associated infections (VAI) continue to cause significant morbidity. In this study, we evaluated the efficacy of antibiotic-coated EVD (AC-EVD) in reducing the occurrence of VAI. Between July 2007 and July 2009, 203 patients underwent placement of an EVD. A total of 145 of these patients met the inclusion criteria, with 76 patients (52.4%) receiving AC-EVD and 69 patients (47.6%) receiving uncoated EVD. Ten patients (6.9%) developed VAI, of whom three were in the AC-EVD group and seven were in the uncoated EVD group (p=0.19). The mean duration between catheter insertion and positive cerebrospinal fluid culture was significantly greater in the AC-EVD group versus the uncoated EVD group (154days versus 42days, respectively; p=0.001). In the uncoated EVD group, 17 of 69 patients (24.6%) were dead at 3years versus 12 of 76 (15.8%) patients in the AC-EVD group (p=0.21). The overall VAI rate was 6.9% with a trend toward lower infection rates in the AC-EVD group compared to the uncoated EVD group (3.9% versus 10.1%, respectively; p>0.05).

View details for DOI 10.1016/j.jocn.2013.09.002

View details for Web of Science ID 000335805500011

View details for PubMedID 24411330

Abstract

Autonomic shift (AS), characterized by increased sympathetic nervous system activation, has been implicated in neurologically mediated cardiopulmonary dysfunction and immunodepression after stroke. We investigated the prevalence of AS defined by readily available clinical parameters and determined the association of AS with subsequent infection in a cohort of patients with aneurysmal subarachnoid hemorrhage (aSAH).Data were obtained from a single-center cohort study of aSAH patients admitted from January 1, 2007, through April 1, 2012. AS was defined as at least 1 early (<72hours) routine clinical marker of neurologically mediated cardiopulmonary dysfunction based on electrocardiogram, echocardiogram, cardiac enzymes, or neurogenic pulmonary edema. Multivariable logistic regression models were developed to evaluate the association between AS and subsequent infection after adjusting for other covariates.A total of 167 patients were included in the analysis (mean age 56, 27% men). AS was seen in 66 of 167 patients (40%; 95% confidence interval [CI], 32%-47%), and infection was seen in 80 of 167 patients (48%; 95% CI, 40%-55%). AS was associated with subsequent infection on unadjusted analysis (odds ratio [OR] 2.11; 95% CI, 1.12-3.97); however, this association was no longer significant when adjusting for other predictors of infection (OR 1.36; 95% CI, .67-2.76). Age, clinical grade, and aneurysm location were all independent predictors of infection after aSAH.We identified AS based on readily available clinical markers in 40% of patients with aSAH, though AS defined by these clinical criteria was not an independent predictor of infection. Additional studies may be warranted to determine the optimal definition of AS and the clinical significance of this finding.

View details for DOI 10.1016/j.jstrokecerebrovasdis.2013.09.007

View details for Web of Science ID 000336482000053

View details for PubMedID 24189451

View details for PubMedCentralID PMC4007375

Abstract

As the population ages, clinicians will be faced with difficult decisions regarding treatment of elderly patients presenting with aneurysmal subarachnoid hemorrhage (aSAH). Previous data have led to continued pessimism by some clinicians treating elderly and very elderly patients presenting with aSAH. The aim of this study was to present our experience in the very elderly treated with endovascular coiling after presentation with aSAH.Retrospective review of all patients 80 years of age or older presenting with aSAH who underwent coil embolization. Primary outcomes of interest were functional outcome, as assessed by the Glasgow Outcome Scale score, and inhospital mortality.During the study period, 16 patients aged 80 years or older presenting with aSAH underwent coil embolization; nine (56%) had a poor outcome at the 6 month follow-up while seven (44%) had a good outcome. The inhospital mortality rate was 50%. Of those patients alive at discharge, seven out of eight (88%) patients had a good outcome. Variables associated with poor outcome included higher Hunt and Hess score (p=0.010), use of balloon assistance/remodeling (p=0.025), and presence of coronary artery disease (p=0.006).Not surprisingly, we found that very elderly patients presenting with aSAH have a high inhospital mortality rate. However, those patients who survive to discharge have a surprisingly robust chance at good functional recovery when treated with coil embolization. We believe these results support offering endovascular coil embolization, when feasible, to very elderly patients presenting with aSAH.

View details for DOI 10.1136/neurintsurg-2013-010714

View details for Web of Science ID 000332609900012

View details for PubMedID 23535264

Abstract

Reported biochemical remission rates following surgical intervention for acromegaly range from 38 to 83%. In patients not achieving surgical remission, few options remain, mostly limited to medical management and radiation therapy. There is debate over whether or not to offer reoperation to patients in whom surgical remission is not achieved with initial resection. Retrospective chart review was undertaken to determine all patients having acromegaly with persistently elevated GH and/or IGF-1 levels after initial pituitary adenoma resection, and who underwent reoperation using endoscopic endonasal approach at a single institution. Biochemical remission was defined as a postoperative GH level <1 ng/mL and a normal postoperative IGF-1 level in the absence of any medical therapy. In total, 14 patients underwent repeat surgical intervention for acromegaly via endoscopic transsphenoidal approach. Of the 14 patients, 8 (57%) achieved biochemical remission following repeat surgical intervention. Lower preoperative GH levels were associated with greater chance of biochemical remission (P = 0.048). New endocrinopathies were seen in 2 patients (14%), and both were transient diabetes insipidus. Meningitis occurred in 2 patients (14%); both were aseptic meningitis with no sequelae. No mortality was encountered. Repeat surgical intervention for acromegaly via endoscopic transsphenoidal approach appears safe and effective. With no mortality and minimal morbidity, repeat surgical intervention via endoscopic transsphenoidal approach appears a reasonable option for these hard-to-treat patients and should be considered for patients in whom surgical remission is not achieved with initial surgery.

View details for DOI 10.1007/s11102-012-0457-x

View details for Web of Science ID 000326891400005

View details for PubMedID 23307479

Abstract

The objective of this study was to compare the accuracy of 3 methods of ventricular catheter placement during CSF shunt operations: the freehand technique using surface anatomy, ultrasonic guidance, and stereotactic neuronavigation.This retrospective cohort study included all patients from a single institution who underwent a ventricular CSF shunting procedure in which a new ventricular catheter was placed between January 2005 and March 2010. Data abstracted for each patient included age, sex, diagnosis, method of ventricular catheter placement, site and side of ventricular catheter placement, Evans ratio, and bifrontal ventricular span. Postoperative radiographic studies were reviewed for accuracy of ventricular catheter placement. Medical records were also reviewed for evidence of shunt failure requiring revision through December 2011. Statistical analysis was then performed comparing the 3 methods of ventricular catheter placement and to determine risk factors for inaccurate placement.There were 249 patients included in the study; 170 ventricular catheters were freehand passed, 51 were placed using stereotactic neuronavigation, and 28 were placed under intraoperative ultrasonic guidance. There was a statistically significant difference between freehand catheters and stereotactic-guided catheters (p<0.001), as well as between freehand catheters and ultrasound-guided catheters (p<0.001). The only risk factor for inaccurate placement identified in this study was use of the freehand technique. The use of stereotactic neuronavigation and ultrasonic guidance reduced proximal shunt failure rates (p<0.05) in comparison with a freehand technique.Stereotactic- and ultrasound-guided ventricular catheter placements are significantly more accurate than freehand placement, and the use of these intraoperative guidance techniques reduced proximal shunt failure in this study.

View details for DOI 10.3171/2012.11.JNS111384

View details for PubMedID 23330995

Abstract

To compare cumulative complication rates of peripherally (PICC) and centrally (CICVC) inserted central venous catheters, including catheter-related large vein thrombosis (CRLVT), central line-associated bloodstream infection (CLABSI), and line insertion-related complications in neurological intensive care patients.Retrospective cohort study and detailed chart review for 431 consecutive PICCs and 141 CICVCs placed in patients under neurological intensive care from March 2008 through February 2010. Cumulative incidence of CRLVT, CLABSI, and line insertion-related complications were compared between PICC and CICVC groups. Risk factors for CRLVT including mannitol therapy during dwell time, previous history of venous thromboembolism, surgery longer than 1h during dwell time, and line placement in a paretic arm were also compared between groups.During the study period, 431 unique PICCs were placed with cumulative incidence of symptomatic thrombosis of 8.4%, CLABSI 2.8%, and line insertion-related complications 0.0%. During the same period, 141 unique CICVCs were placed with cumulative incidence of symptomatic thrombosis of 1.4%, CLABSI 1.4%, and line insertion-related complications 0.7%. There was a statistically significant difference in CRLVT with no difference in CLABSI or line insertion-related complications.In neurological critical care patients, CICVCs appear to have a better risk profile compared to PICCs, with a decreased risk of CRLVT. As use of PICCs in critical care patients increases, a prospective randomized trial comparing PICCs and CICVCs in neurological critical care patients is necessary to assist in choosing the appropriate catheter and to minimize risks of morbidity and mortality associated with central venous access.

View details for DOI 10.1016/j.clineuro.2012.08.025

View details for Web of Science ID 000321403000006

View details for PubMedID 22948189

Abstract

Diseases of the nervous system have devastating effects and are widely distributed among the population, being especially prevalent in the elderly. These diseases are often caused by inherited genetic mutations that result in abnormal nervous system development, neurodegeneration, or impaired neuronal function. Other causes of neurological diseases include genetic and epigenetic changes induced by environmental insults, injury, disease-related events or inflammatory processes. Standard medical and surgical practice has not proved effective in curing or treating these diseases, and appropriate pharmaceuticals do not exist or are insufficient to slow disease progression. Gene therapy is emerging as a powerful approach with potential to treat and even cure some of the most common diseases of the nervous system. Gene therapy for neurological diseases has been made possible through progress in understanding the underlying disease mechanisms, particularly those involving sensory neurons, and also by improvement of gene vector design, therapeutic gene selection, and methods of delivery. Progress in the field has renewed our optimism for gene therapy as a treatment modality that can be used by neurologists, ophthalmologists and neurosurgeons. In this Review, we describe the promising gene therapy strategies that have the potential to treat patients with neurological diseases and discuss prospects for future development of gene therapy.

View details for DOI 10.1038/nrneurol.2013.56

View details for Web of Science ID 000318851000008

View details for PubMedID 23609618

View details for PubMedCentralID PMC3908892

Abstract

The authors conducted a study to review outcomes and management in patients in whom intracranial hemorrhage (ICH) develops during left ventricular assist device (LVAD) therapy.This retrospective cohort study included all adult patients (18 years of age or older) at a single institution who underwent placement of an LVAD between January 1, 2003, and March 1, 2012. The authors conducted a detailed medical chart review, and data were abstracted to assess outcomes in patients in whom ICH developed compared to those in patients in whom ICH did not develop; to compare management of antiplatelet agents and anticoagulation with outcomes; to describe surgical management employed and outcomes achieved; to compare subtypes of ICH (intraparenchymal, subdural, and subarachnoid hemorrhage) and their outcomes; and to determine any predictors of outcome.During the study period, 330 LVADs were placed and 36 patients developed an ICH (traumatic subarachnoid hemorrhage in 10, traumatic subdural hematoma in 8, spontaneous intraventricular hemorrhage in 1, and spontaneous intraparenchymal hemorrhage in 17). All patients were treated with aspirin and warfarin at the time of presentation. With suspension of these agents, no thromboembolic events or pump failures were seen and no delayed rehemorrhages occurred after resuming these medications. Intraparenchymal hemorrhages had the worst outcomes, with a 30-day mortality rate in 59% compared with a 30-day mortality rate of 0% in patients with traumatic subarachnoid hemorrhages and 13% in those with traumatic subdural hematomas. Five patients with intraparenchymal hemorrhages were managed with surgical intervention, 4 of whom died within 60 days. The only factor found to be predictive of outcome was initial Glasgow Coma Scale score. No patients with a Glasgow Coma Scale score less than 11 survived beyond 30 days. Overall, the development of an ICH significantly reduced survival compared with the natural history of patients on LVAD therapy.The authors' data suggest that withholding aspirin for 1 week and warfarin for 10 days is sufficient to reduce the risk of hemorrhage expansion or rehemorrhage while minimizing the risk of thromboembolic events and pump failure. Patients with intraparenchymal hemorrhage have poor outcomes, whereas patients with traumatic subarachnoid hemorrhage or subdural hematoma have better outcomes.

View details for DOI 10.3171/2013.1.JNS121849

View details for PubMedID 23451903

Abstract

Bilateral vertebral artery dissecting aneurysms (VADAs) presenting with subarachnoid haemorrhage (SAH) are an exceedingly rare and deadly clinical dilemma. Prompt intervention in the case of unilateral VADAs is advocated to prevent rebleed; however, in the case of bilateral VADAs, the optimal therapeutic intervention is unclear. We describe the case of a patient presenting with SAH with bilateral VADAs treated by staged endovascular stenting. This led to resolution of the aneurysms with patency of both vertebral arteries. Stent-based therapy of the symptomatic aneurysm followed by staged stenting of the asymptomatic, contralateral aneurysm appears to be a viable treatment option. This method allows the ability to preserve flow in both vertebral arteries with minimal changes in flow characteristics that may threaten the contralateral, asymptomatic VADA, and appears to be the ideal treatment in these rare cases.

View details for DOI 10.1136/bcr-03-2012-6002

View details for PubMedID 23417929

View details for PubMedCentralID PMC3603424

Abstract

We report the unusual case of a patient with an indirect carotid-cavernous fistula treated with only partial angiographic embolisation of the fistula; however, by 8 weeks postembolisation, she was found to have both symptomatic and angiographic cure. This case highlights the potential for treating indirect carotid-cavernous fistulas with partial embolisation as a means of achieving angiographic and symptomatic cure by altering flow dynamics to attain spontaneous thrombosis.

View details for DOI 10.1136/bcr-03-2012-6004

View details for PubMedID 23008364

View details for PubMedCentralID PMC4543146

Abstract

In patients who undergo neurovascular stent placement with postoperative dual antiplatelet therapy to prevent in-stent thrombosis, there is no protocol for balancing the risk of acute stent thrombosis and bleeding if urgent neurosurgical procedures are required. We detail perioperative management of dual antiplatelet therapy in a 66-year-old man with a dolichoectatic aneurysm of the basilar artery treated with a Pipeline stent. Postoperatively, the patient was placed on aspirin and clopidogrel to prevent in-stent thrombosis. One month after the procedure, his neurological status declined secondary to obstructive hydrocephalus. His condition necessitated urgent placement of a ventriculoperitoneal shunt, despite the dual antiplatelet therapy for the flow-diverting Pipeline stent. Aspirin and clopidogrel were discontinued seven days prior to the planned shunt placement. To minimize time off antiplatelet therapy, aspirin was immediately replaced with ibuprofen. Eptifibatide was then started three days prior to surgery. The ibuprofen/eptifibatide bridge was discontinued at midnight prior to surgery. Aspirin was restarted on the first postoperative day and clopidogrel was restarted on the second postoperative day. The patient tolerated shunt placement without excessive bleeding or hemorrhagic complications. During the remainder of his hospital course, no evidence of stent thrombosis or intracranial hemorrhage was noted. We conclude that management of antiplatelet prophylaxis for neurovascular stent thrombosis in patients requiring urgent neurosurgical procedures may be successfully achieved by bridging aspirin and clopidogrel with ibuprofen and eptifibatide in the preoperative period.

View details for DOI 10.1016/j.jocn.2011.12.018

View details for PubMedID 22784876

Abstract

The overwhelming majority of pineal region tumors are malignant germ cell tumors, pineal cell tumors, or glial tumors. To our knowledge we report the first patient with myeloid sarcoma in the pineal region. Myeloid sarcomas are composed of immature granulocytic precursor cells and are associated with acute myelogenous leukemia. Thus, myeloid sarcoma should be considered in the differential diagnosis of pineal region masses in patients with a known history of acute myelogenous leukemia.

View details for DOI 10.1016/j.jocn.2011.11.014

View details for Web of Science ID 000311323800025

View details for PubMedID 22560847

Abstract

Meningiomas often are not amenable to total resection, and subtotally resected meningiomas often recur. Recurrent meningiomas present a clinical dilemma, particularly when surgical and radiotherapy options are exhausted, as there are no chemotherapeutic options that demonstrate consistent, significant efficacy. We report a patient with the regression of a recurrent World Health Organization grade I meningioma during combination chemotherapy with bevacizumab and paclitaxel for breast cancer. This chemotherapy regimen has never been explored for recurrent meningiomas. While further data are necessary, we suggest that combination chemotherapy with bevacizumab and paclitaxel may be an option for treatment of recurrent meningiomas when no further surgical or radiotherapy options exist.

View details for DOI 10.1016/j.jocn.2011.07.024

View details for Web of Science ID 000301165100029

View details for PubMedID 22245272

Abstract

Using Virchow's triad as a framework, we sought to identify risk factors independently associated with symptomatic peripherally inserted central venous catheter (PICC)-related large vein thrombosis (PRLVT) in neurological intensive care patients.A retrospective cohort study and detailed chart review were performed for 431 consecutive PICCs placed in patients admitted to our neurological intensive care unit between March 2008 and February 2010. Variables theorized to potentially increase the risk of PRLVT were abstracted from the medical record. Each variable was then tested for its independent association with PRLVT.During the study period, 431 PICCs were placed with an incidence rate for symptomatic thrombosis of 8.4%. In adjusted analysis, catheter placement in a paretic arm (OR, 9.85; 95% CI, 4.42-21.95), surgery longer than 1h during dwell time of the catheter (OR, 3.26; 95% CI, 1.48-7.17), a history of venous thromboembolism (OR, 6.66; 95% CI, 2.38-18.62), and mannitol use (OR, 3.27; 95% CI 1.27-8.43) were independently associated with the development of thrombosis.Alterations in blood flow and consistency, but not vessel injury, appear associated with symptomatic thrombosis following placement of PICCs in neurological intensive care patients. Mannitol use and placement in a paretic arm are potentially modifiable risk factors. Given the high incidence rate of symptomatic thrombosis, future studies should focus on comparing cumulative complications of centrally inserted venous catheters and PICCs in intensive care patients.

View details for DOI 10.1007/s00134-011-2418-7

View details for Web of Science ID 000299501700012

View details for PubMedID 22113818

Abstract

Thoracic vertebral compression fractures are a known complication of generalized tetanus. The authors report the first known case of an L-2 burst fracture leading to cauda equina syndrome, as a result of generalized tetanus. This 51-year-old man had generalized tetanus with a constellation of symptoms including compartment syndrome requiring fasciotomies, severe axial spasms and spasms of the extremities, autonomic dysreflexia, hypercarbic respiratory failure, and rhabdomyolysis. During the course of his illness, areflexic paraparesis developed in his lower extremities. He was found to have an L-2 burst fracture with retropulsion of a bone fragment resulting in cauda equina syndrome. Operative intervention was undertaken to decompress the cauda equina and stabilize the spine. The natural progression of tetanus can be complex, with a mixed picture ranging from spasms plus increased tone and reflexes to reduced tone and reflexes as presynaptic nerve terminals become damaged. The authors suggest that all sudden changes in the neurological examination should prompt consideration of diagnostic imaging before attributing such changes to natural progression of the disease.

View details for DOI 10.3171/2011.7.SPINE11335

View details for Web of Science ID 000298631100018

View details for PubMedID 21854128

Abstract

The aim of this article was to report on the nature and prevalence of incidental imaging findings in a consecutive series of patients older than 90 years of age who underwent intracranial imaging for any reason.The authors retrospectively reviewed the electronic medical and imaging records of consecutive patients who underwent brain MR imaging at a single institution over a 153-month interval and were at least 90 but less than 100 years of age at the time of the imaging study. The prevalence of lesions by type in this consecutive series of MR imaging evaluations was calculated for all patients. The authors reviewed the medical record to evaluate whether a change in management was recommended based on MR imaging findings. They evaluated patient age at the time of death and the time interval between MR imaging and death.The authors identified 177 patients who met the study criteria. The group included 119 women (67%) and 58 (33%) men. Their mean age was 92.3 1.8 years. Evidence of acute ischemic changes or cerebrovascular accident (CVA) was found in 36 patients (20%). Fifteen patients (8%) had an intracranial tumor. Intracranial aneurysms were incidentally identified in 6 patients (3%). Chronic subdural hematomas were found in 3 patients (2%). Overall, 25 patients (14%) had some change in medical management as a result of the MR imaging findings. The most common MR imaging finding that resulted in a change in medical management was an acute CVA (p < 0.0001). The mean time to death from date of MR imaging was 2.5 2.3 years.Intracranial imaging is rarely performed in patients older than 90 years. In cases of suspected stroke, MR imaging findings may influence treatment decisions. Brain MR imaging studies ordered for other indications in this age group rarely influence treatment decisions. Incidentally discovered lesions in this age group are generally not treated.

View details for DOI 10.3171/2011.9.FOCUS11205

View details for Web of Science ID 000297743200013

View details for PubMedID 22133167

Abstract

Peripherally inserted central venous catheters (PICCs) are being increasingly utilized in hospitalized patients as alternatives to centrally inserted central venous catheters (CICVCs). However, concern exists over the risk of PICC-related large vein thrombosis (PRLVT). The incidence rate and significance of symptomatic PRLVT in critically ill patients admitted to the neurological intensive care unit (ICU) is not known.Retrospective descriptive study of consecutive PICCs placed in critically ill patients admitted to a tertiary care neurological ICU between March 2008 and February 2010. Symptomatic PRVLT was defined as an event that prompted Duplex ultrasound of the ipsilateral extremity in which an acute, proximal large vein thrombosis was confirmed in association with the PICC or confirmed within 5days of PICC removal. Incidence rate of PRLVT and catheter-related complications were calculated per "line" (catheter). Descriptive statistics were performed with two-sample, and t-tests for age and categorical variables were assessed by Chi-square test or Fishers exact test as appropriateFour hundred and seventy-nine lines were placed during the study period with 39 developing a symptomatic PRLVT (incidence rate=8.1%). Male gender was associated with development of a thrombosis (P=0.02), but size (P=0.21) and location of catheter were not (P=0.30). Median line dwell time was 12days (IQR 16) with a dwell time of 8days (IQR 9) until thrombosis diagnosis. Pulmonary embolus attributed to PRLVT occurred in 1.3% of line placements and 15% of symptomatic PRLVT. The majority of patients had their line removed. In addition, some patients also had anticoagulation initiated or a superior vena cava filter placed.Symptomatic PRLVT is not uncommon in critically ill patients admitted to the neurological ICU. Future research should focus on indentifying modifiable risk factors for PRLVT and on comparing major cumulative complication rates between PICCs and CICVCs.

View details for DOI 10.1007/s12028-011-9554-3

View details for Web of Science ID 000297365400015

View details for PubMedID 21541826

Abstract

Radiographic findings of hyperglycemic non-ketotic chorea-hemiballismus and basal ganglia hemorrhage can be highly similar. A 58-year-old female presented with a 1-week history of choreiform and ballistic movements of the left arm. Based on CT imaging, the patient was diagnosed with a basal ganglia hemorrhage. After transfer to our institution, further imaging and work-up led to a diagnosis of non-ketotic hyperglycemic chorea-hemiballismus. Aggressive glycemic control was started and the patient's symptoms resolved. Despite its rarity, non-ketotic hyperglycemic chorea-hemiballismus should be included in the differential diagnosis of basal ganglia hyperdensity on CT scan, as it can mimic basal ganglia hemorrhage. Resolution of this clinical entity and implementation of aggressive glycemic control can lead to complete resolution of symptoms. It is important for neurosurgeons to be aware of this clinical entity as prompt treatment often yields good outcomes.

View details for DOI 10.1016/j.jocn.2011.03.010

View details for Web of Science ID 000296402800035

View details for PubMedID 21871808

Abstract

The goal of this study was to review the literature to compare strategies for avoiding and treating complications from anterior lumbar interbody fusion (ALIF), and thus provide a comprehensive aid for spine surgeons. A thorough review of databases from the US National Library of Medicine and the National Institutes of Health was conducted. The complications of ALIF addressed in this paper include pseudarthrosis and subsidence, vascular injury, retrograde ejaculation, ileus, and lymphocele (chyloretroperitoneum). Strategies identified for improving fusion rates included the use of frozen rather than freeze-dried allograft, cage instrumentation, and bone morphogenetic protein. Lower cage heights appear to reduce the risk of subsidence. The most common vascular injury is venous laceration, which occurs less frequently when using nonthreaded interbody grafts such as iliac crest autograft or femoral ring allograft. Left iliac artery thrombosis is the most common arterial injury, and its occurrence can be minimized by intermittent release of retraction intraoperatively. The risk of retrograde ejaculation is significantly higher with laparoscopic approaches, and thus should be avoided in male patients. Despite precautionary measures, complications from ALIF may occur, but treatment options do exist. Bowel obstruction can be treated conservatively with neostigmine or with decompression. In cases of postoperative lymphocele, resolution can be attained by creating a peritoneal window. By recognizing ways to minimize complications, the spine surgeon can safely use ALIF procedures.

View details for DOI 10.3171/2011.7.FOCUS11141

View details for Web of Science ID 000295406500007

View details for PubMedID 21961869

Abstract

We report a rare case of thrombosis of the superior sagittal sinus associated with a parafalcine meningioma resulting in a superior sagittal sinus dural arteriovenous fistula (dAVF). We conclude that dural sinus thrombosis is a significant predisposing factor for development of a dAVF.A 60-year-old man had a left parietal parafalcine meningioma that invaded the posterior third of his superior sagittal sinus, leading to its occlusion and presumably resulting in an associated dAVF. The fistula was fed by the middle meningeal and superficial temporal arteries on both sides and drained through a superior interhemispheric cortical vein into the vein of Galen and straight sinus.The parafalcine mass, which involved the sagittal sinus, was excised via a left parieto-occipital craniotomy. It was decided to resect the dAVF at a later date. Seven days after the original operation, the patient underwent a parietal interhemispheric approach for occlusion of the dAVF. Dissection proceeded until a large arterialized vein and venous pouch with multiple feeders from both external carotid arteries were observed. The vein, which was partially embedded within the falx cerebri, was collapsed, and a second indocyanine green injection confirmed cessation of blood flow.This report supports that dAVFs are acquired lesions and that venousoutflow obstruction is a significant contributing factor to their development. In meningiomas associated with the dural sinuses, diagnostic evaluation for possible dAVFs should be considered. Treatment of these lesions should be based on risk factors because spontaneous resolution after tumor excision has been reported.

View details for DOI 10.1227/01.NEU.0000370089.94032.4F

View details for PubMedID 20559067

Abstract

Transforming growth factor (TGF)-beta signaling makes a significant contribution to the pathogenesis of breast cancer bone metastasis. In other tumor types, TGF-beta has been shown to promote tumor vascularity. Here, we report that inhibition of TGF-beta significantly reduces microvessel density in mammary tumor-induced bone lesions, mediated by decreased expression of both vascular endothelial growth factor (VEGF) and monocyte chemotactic protein (MCP)-1, both known angiogenic factors. Cathepsin G upregulation at the tumor-bone interface has been linked to increased TGF-beta signaling, and we also report that inhibition of Cathepsin G reduced tumor vascularity, as well as VEGF and MCP-1 expression.

View details for DOI 10.1016/j.canlet.2009.06.035

View details for Web of Science ID 000275150800004

View details for PubMedID 19646811

View details for PubMedCentralID PMC2815079

Abstract

The bone microenvironment plays a critical role in tumor-induced osteolysis and osteolytic metastasis through tumor-bone (TB)-interaction. Receptor activator of nuclear factor-kappaB (RANK) ligand (RANKL) is one of the critical signaling molecules involved in osteolysis and bone metastasis. However, the regulation and functional significance of RANKL at the TB-interface in tumor-induced osteolysis remains unclear. In this report, we examined the role of tumor-stromal interaction in the regulation of RANKL expression and its functional significance in tumor-induced osteolysis. Using a novel mammary tumor model, we identified that RANKL expression was upregulated at the TB-interface as compared to the tumor alone area. We demonstrate increased generation of sRANKL at the TB-interface, which is associated with tumor-induced osteolysis. The ratio of RANKL to osteoprotegrin (OPG), a decoy receptor for RANKL, at the TB-interface was also increased. Targeting RANKL expression with antisense oligonucleotides (RANKL-ASO), significantly abrogated tumor-induced osteolysis, decreased RANKL expression and the RANKL:OPG ratio at the TB-interface. Together, these results demonstrate that upregulation of RANKL expression and sRANKL generation at the TB-interface potentiates tumor-induced osteolysis.

View details for DOI 10.1007/s10585-009-9279-2

View details for Web of Science ID 000271722300021

View details for PubMedID 19590968

Abstract

Increased transforming growth factor-beta (TGF-beta) signaling has been observed at the tumor-bone interface of mammary tumor-induced osteolytic lesions despite no observed transcriptional up-regulation of TGF-beta. To this point, the mechanism for enhanced TGF-beta signaling remains unclear. The bulk of TGF-beta that is released at the tumor-bone interface is in an inactive form secondary to association with beta-latency-associated protein and latency TGF-beta binding protein. We hypothesized that the observed increase in TGF-beta signaling is due to increased cathepsin G-dependent, matrix metalloproteinase 9 (MMP9)-mediated activation of latent TGF-beta. MMP9 is capable of activating latent TGF-beta, and we observed that decreased production of MMP9 was associated with reduced TGF-beta signaling. Similar to TGF-beta, MMP9 is released in an inactive form and requires proteolytic activation. We showed that cathepsin G, which we have previously shown to be up-regulated at the tumor-bone interface, is capable of activating pro-MMP9. Inhibition of cathepsin G in vivo significantly reduced MMP9 activity, increased the ratio of latent TGF-beta to active TGF-beta, and reduced the level of TGF-beta signaling. Our proposed model based on these results is that cathepsin G is up-regulated through tumor-stromal interactions and activates pro-MMP9, active MMP9 cleaves and releases active TGF-beta, and active TGF-beta can then promote tumor growth and enhance osteoclast activation and subsequent bone resorption. Thus, for the first time, we have identified cathepsin G and MMP9 as proteases involved in enhanced TGF-beta signaling at the tumor-bone interface of mammary tumor-induced osteolytic lesions and have identified these proteases as potential therapeutic targets.

View details for DOI 10.1158/1541-7786.MCR-09-0028

View details for Web of Science ID 000269170200004

View details for PubMedID 19671689

Abstract

Metastatic breast cancer shows extreme tropism for the bone microenvironment, leading to the establishment of osteolytic metastases. Perpetuation of tumor-induced osteolysis requires a continuous supply of osteoclast precursors migrating into the bone microenvironment that can subsequently differentiate into mature osteoclasts and resorb bone. Thus, identification and subsequent targeting of chemoattractants of osteoclast precursors that are up-regulated at the tumor-bone interface represents a potential avenue to interrupt osteolysis. We report that cathepsin G, a serine protease, plays a vital role in the bone microenvironment by modulating tumor-stromal interaction in a manner that favors tumor establishment and regulates chemotaxis of monocytes, a subset of which has the potential to differentiate into osteoclasts. Our data show that cathepsin G-induced chemotaxis of monocytes is mediated by proteolytic activation of protease-activated receptor-1 (PAR-1). Attenuation of PAR-1 activation abrogates cathepsin G-mediated induction of monocyte chemotaxis. We also show that in vivo inhibition of cathepsin G reduces the number of CD11b(+) osteoclast precursors and mature osteoclasts at the tumor-bone interface. Together, these data suggest that therapeutic targeting of both PAR-1 signaling in osteoclast precursors as well as cathepsin G at the tumor-bone interface has the potential to reduce osteolysis by inhibiting the recruitment, differentiation, and activation of osteoclast precursors.

View details for DOI 10.1158/0008-5472.CAN-08-1956

View details for Web of Science ID 000264908100064

View details for PubMedID 19293192

Abstract

Breast cancer commonly causes osteolytic metastases in bone, a process that is dependent on tumor-stromal interaction. Proteases play an important role in modulating tumor-stromal interactions in a manner that favors tumor establishment and progression. Whereas several studies have examined the role of proteases in modulating the bone microenvironment, little is currently known about their role in tumor-bone interaction during osteolytic metastasis. In cancer-induced osteolytic lesions, cleavage of receptor activator of nuclear factor-kappaB ligand (RANKL) to a soluble version (sRANKL) is critical for widespread osteoclast activation. Using a mouse model that mimics osteolytic changes associated with breast cancer-induced bone metastases, we identified cathepsin G, cathepsin K, matrix metalloproteinase (MMP)-9, and MMP13 to be proteases that are up-regulated at the tumor-bone interface using comparative cDNA microarray analysis and quantitative reverse transcription-PCR. Moreover, we showed that cathepsin G is capable of shedding the extracellular domain of RANKL, generating active sRANKL that is capable of inducing differentiation and activation of osteoclast precursors. The major source of cathepsin G at the tumor-bone interface seems to be osteoclasts that up-regulate production of cathepsin G via interaction with tumor cells. Furthermore, we showed that in vitro osteoclastogenesis is reduced by inhibition of cathepsin G in a coculture model and that in vivo inhibition of cathepsin G reduces mammary tumor-induced osteolysis. Together, our data indicate that cathepsin G activity at the tumor-bone interface plays an important role in mammary tumor-induced osteolysis and suggest that cathepsin G is a potentially novel therapeutic target in the treatment of breast cancer bone metastasis.

View details for DOI 10.1158/0008-5472.CAN-07-5889

View details for Web of Science ID 000257768300038

View details for PubMedID 18632634

Abstract

As cells undergo oncogenic transformation and as malignant cells arrive at metastatic sites, a complex interplay occurs with the surrounding stroma. This dialogue between the tumor and stroma ultimately dictates the success of the tumor cells in the given microenvironment. As a result, understanding the molecular mechanisms at work is important for developing new therapeutic modalities. Proteases are major players in the interaction between tumor and stroma. This review will focus on the role of proteases in modulating tumor-stromal interactions of both primary breast and prostate tumors as well as at bone metastatic sites in a way that favors tumor growth.

View details for DOI 10.1016/j.bbcan.2007.11.001

View details for Web of Science ID 000256211800001

View details for PubMedID 18082147

View details for PubMedCentralID PMC2418859