Christopher Baggott

The role of cation-dependent chloride transporters in neuropathic pain following spinal cord injury

BackgroundAltered Cl- homeostasis and GABAergic function are associated with nociceptive input hypersensitivity. This study investigated the role of two major intracellular Cl- regulatory proteins, Na+-K+-Cl- cotransporter 1 (NKCC1) and K+-Cl- cotransporter 2 (KCC2), in neuropathic pain following spinal cord injury (SCI).ResultsSprague-Dawley rats underwent a contusive SCI at T9 using the MASCIS impactor. The rats developed hyperalgesia between days 21 and 42 post-SCI. Thermal hyperalgesia (TH) was determined by a decrease in hindpaw thermal withdrawal latency time (WLT) between days 21 and 42 post-SCI. Rats with TH were then treated with either vehicle (saline containing 0.25% NaOH) or NKCC1 inhibitor bumetanide (BU, 30 mg/kg, i.p.) in vehicle. TH was then re-measured at 1 h post-injection. Administration of BU significantly increased the mean WLT in rats (p < 0.05). The group administered with the vehicle alone showed no anti-hyperalgesic effects. Moreover, an increase in NKCC1 protein expression occurred in the lesion epicenter of the spinal cord during day 2–14 post-SCI and peaked on day 14 post-SCI (p < 0.05). Concurrently, a down-regulation of KCC2 protein was detected during day 2–14 post-SCI. The rats with TH exhibited a sustained loss of KCC2 protein during post-SCI days 21–42. No significant changes of these proteins were detected in the rostral region of the spinal cord.ConclusionTaken together, expression of NKCC1 and KCC2 proteins was differentially altered following SCI. The anti-hyperalgesic effect of NKCC1 inhibition suggests that normal or elevated NKCC1 function and loss of KCC2 function play a role in the development and maintenance of SCI-induced neuropathic pain.

How reliable and accurate is indocyanine green video angiography in the evaluation of aneurysm obliteration

INTRODUCTION Indocyanine green video angiography (ICG-VA) has been recently introduced into neurovascular surgery and gained a role in assessing vessel patency and obliteration of intracranial aneurysms (IA) after clipping. Although its correlation with intra-postoperative angiography was demonstrated in previous studies, difficulties in evaluating aneurysm obliteration have not been reported. We report reliability and accuracy of ICG-VA in 109 clipped aneurysms with attention given to five cases in which ICG-VA evaluation resulted in false indication that aneurysms were secure in terms of complete obliteration. MATERIALS AND METHODS A retrospective chart review was performed of IAs surgically treated by a single surgeon from January 2009. In all cases, aneurysm obliteration was confirmed by a combination of microdoppler ultrasonography (MUSG), ICG-VA, and post-operative angiography. RESULTS ICG-VA appropriately assessed vessel patency and aneurysm obliteration in 93.5% of aneurysms clipped. In four cases (3.6%), puncturing the dome of the aneurysm after satisfactory clipping revealed persistent flow within the aneurysm despite ICG-VA showing no flow after clipping. In one case (0.9%), ICG-VA showed persistent flow within the aneurysm and MUSG did not, and puncture of the dome confirmed no flow within the aneurysm. In one case (0.9%), ICG-VA failed to demonstrate residual neck. CONCLUSION ICG-VA is a simple and safe procedure and an important adjunct to microsurgical clipping of aneurysm. Although ICG-VA assesses vessel patency and obliteration of aneurysms in most cases, applying the principles of microsurgery in aneurysm clipping remains a main tool for obtaining the complete obliteration of aneurysm along with preservation of the normal vasculature.

Reliable time to estimate subglottal pressure.

Measuring subglottal pressure (P(s)) with complete interruption can be problematic due to unsteady plateaus in supraglottal pressure data traces during balloon valve interruption. Subjectively determining when the graph plateaus neglect the effects of laryngeal, auditory, and other physical reflexes may alter patient effort and glottal configuration. If the P(s) estimation was made at a consistent time before the onset of reflexes, the recorded pressure would not be dependent on subjective analysis by a clinician, and intrasubject data would be more precise. Previously collected data using the airflow interruption system have shown consistency at approximately 150 milliseconds after balloon valve inflation. To evaluate the validity of estimating P(s) at this point, a theoretical and a physical model were applied. A theoretical ideal gas model of capacitance calculated the time necessary for supraglottal pressure to equilibrate with P(s). Using a mechanical pseudolung which served as a constant pressure source, known subresistor pressures were compared to the pressure measured by the interruption device. Both models confirmed the validity of measuring P(s) consistently at 150 milliseconds into the 500-millisecond interruption. In human trials testing 25 subjects, mean intrasubject standard deviation using this optimal time constant was 0.66+/-0.37cm H(2)O, and 1.11+/-0.48cm H(2)O when performing plateau analysis (P<0.0005). This novel modification to the clinically feasible interruption model for P(s) estimation demonstrates a marked improvement in the reliability of balloon valve interruption while maintaining the validity demonstrated in previous studies.

Demographic, circadian, and climatic factors in non-aneurysmal versus aneursymal subarachnoid hemorrhage

BACKGROUND Although, the relationship of spontaneous subarachnoid hemorrhage (SAH) to climatic or circadian factors has been widely studied, epidemiologic, circardian and climatic factors in non-aneurysmal SAH (naSAH), particularly perimesencephalic SAH (PMH), has not been reported before. OBJECTIVE For the first time, demographic, climatic, and circadian variables are examined together as possible contributing factors comparing aSAH and naSAH. METHODS We reviewed records for 384 patients admitted to University of Wisconsin Neurosurgery Service from January 2005 to December 2010 with spontaneous non-traumatic SAH. Patients were grouped as aSAH (n=338) or naSAH (n=46) on clinical and radiological criteria. PMH (n=32) was identified as a subgroup of naSAH based on radiological criteria. We logged demographic data, time of SAH, temperature at onset and atmospheric pressure at onset. The three subgroups were compared. RESULTS Aneurysmal SAH occurred most often from 6am to 12pm (p<0.001); this correlation was not found in naSAH or PMH subgroups. Demographic analysis demonstrated predominance of female gender (p=0.008) and smoking (p=0.002) in aSAH, with predominance of hypercholesterolemia in naSAH (p=0.033). Atmospheric pressure, correlated with aSAH in the main county referral area, where we had detailed weather data (p<0.05); however, there was no weather correlation in the entire referral region taken together. Multivariate analysis supported a statistical difference only in smoking status between aSAH and naSAH groups (p=0.0159). CONCLUSION Statistical differences in gender, smoking status, and history of hypercholesterolemia support a clinical distinction between aSAH and naSAH. Furthermore, circadian patterning of aSAH is not reproduced in naSAH, supporting pathophysiologic differences. Only smoking status provides a robust difference in aSAH and naSAH groups. Our data prompt further investigation into the relationship between aSAH and atmospheric pressure.

Estimating Subglottal Pressure via Airflow Redirection

Subglottal pressure (SGP) is a valuable parameter in the research and clinical assessment of laryngeal function. The lungs serve as a constant pressure source during sustained phonation, and that pressure, SGP, can be used to determine the efficiency with which the larynx converts aerodynamic power to acoustic power. As the larynx serves as an aerodynamic transducer, the vocal efficiency (Ve) coefficient, defined as acoustic power (dB) divided by aerodynamic power (SGP × glottal airflow) has been shown to reliably reflect vocal health. However, current SGP measurement techniques are hesitantly used because of either an invasive nature or the requirement of intensive patient training. This study tests a novel device that has been designed to noninvasively estimate SGP through mechanical airflow redirection, producing a numeric output on completion of the trial, which lasts only a few seconds. The novelty of this design lies in the ease of use for both the patient and the clinician. Multiple mechanical airflow redirections occlude the airway for only 135 ms, which is predicted to limit the effect of confounding laryngeal reflexes that may occur during the trials. Additionally, the airflow redirection into a retention device allows for the pneumatic in‐trial comparison of the estimated SGP with the pressure achieved by the patient, providing a numeric output to the clinician on completion.

Recent Developments in the Study of Spinal Cord Injury and Neuropathic Pain

Spinal cord injury (SCI) represents a profound clinical problem for which there exists limited effective therapy. The clinical management of SCI is frequently complicated by the subsequent development of chronic neuropathic pain syndromes. The pathogenesis of central neuropathic pain following SCI is unclear, although evidence exists for the involvement of a diverse range of factors. Key mediators of neuropathic pain include the inflammatory process, excitatory neurotransmitters, opioid and cannabinoid receptors, and ion channel activity. Recent studies conducted in animal models have yielded promising results for the development of neuropathic pain therapies that target these mediators, but clinical results have been disappointing. In this review, we provide an overview of current animal models of SCI and neuropathic pain, discuss recent advances in the study of the aforementioned neuropathic pain mediators, and review the current clinical treatment of neuropathic pain with emphasis on areas that show promise for future investigation. doi: 10.5214/ans.0972.7531.2007.140403

How I do it: treatment of blood blister-like aneurysms of the supraclinoid internal carotid artery by extracranial-to-intracranial bypass and trapping

BackgroundBlood blister-like aneurysms (BBAs) pose a significant challenge to neurosurgeons and neuro-interventionalists. These fragile broad-based aneurysms have a propensity to rupture with minimal manipulation during surgical or endovascular explorations because, unlike saccular aneurysms, they lack all layers of the arterial wall. Aneurysm trapping with extracranial-intracranial (EC-IC) bypass is a safe and durable treatment for BBAs.MethodsWe describe our technique and the guiding principles for surgical bypass and trapping of BBAs of the supraclinoid internal carotid artery (ICA).ConclusionsTreatment of BBAs of the supraclinoid ICA remains difficult. Aneurysm trapping with EC-IC bypass treats BBAs definitively by eliminating the diseased segment of the ICA. We have found the technique and principles described here to be safe and durable in our hands.

Blood Blister-Like Aneurysms of the Intracranial Arteries

An aneurysm is an abnormal dilation of a blood vessel caused by a weakness in the wall of the artery, which puts it at risk for rupture. In most populations, the prevalence of intracranial aneurysms ranges from 1% to 6%. Most cerebral aneurysms are categorized as saccular, fusiform, or dissecting types. Saccular aneurysms, which are seen most frequently at cerebral artery bifurcations, are the most common cause of spontaneous subarachnoid hemorrhage (SAH), although only 0.7% to 1.9% of all cerebral aneurysms rupture. Fusiform aneurysms and dissecting aneurysms are less common. Blood blister-like aneurysms (BBLAs) represent a unique class of aneurysms. Although the term “blood blister-like aneurysm” is used to describe various aneurysms including sessile, broad-based saccular aneurysms at nonbranching sites, and dissecting aneurysms involving either a short or a long segment of the supraclinoid internal carotid artery (ICA), there is debate regarding the histopathologic relationship of the BBLA to saccular or dissecting aneurysms. Most authors think that BBLAs arise from a tear in the vessel wall, contained after rupture by only fragmented adventitia and clot. There are noticeable differences from other ruptured cerebral aneurysms in the risk of rerupture, in treatment strategy, and in the high rate of mortality. BBLAs are defi ned as small, hemispheric lesions protruding from nonbranching sites on the ICA. Extremely thin, fragile walls, poorly defi ned necks, and a high tendency to rupture characterize these aneurysms. Although several reports have been published regarding the diagnosis and treatment of BBLAs, optimal management strategy remains unclear. Moreover, the natural history of BBLAs remains incompletely understood. The aim of this report is to review the available literature regarding this challenging and dangerous clinical entity.

What is the optimal venous thromboembolism prophylaxis for gynecological oncology patients with CNS metastases

Gynecological malignancies such as ovarian cancer increase the risk of venous thromboembolism (VTE) in patients, with reports suggesting that the odds of developing a pulmonary embolism after a major abdominal surgery are elevated 14-fold in patients suffering from malignant diseases versus benign lesions [1]. Less than 2% of ovarian cancer patients are diagnosed with central nervous system (CNS)metastatic disease [2]. However, since therapeutic advances are extending survival of gynecologic cancer patients (just as with lung and breast cancer patients), it is expected that an increasing number of patients will be diagnosed with CNS metastases and considered for neurosurgical resection via craniotomy or spinal laminectomies. Since many patients with ovarian cancer are hypercoagulable, perioperative VTE prophylaxis is a challenging and important clinical questionwhen considering major neurosurgical procedures involving large wounds, prolonged surgeries and attendant risks of possible perioperative hemorrhage resulting in catastrophic neurological deficits. There are inherent concerns with broad extrapolation and application of general surgery or oncology VTE prevention guidelines to neurosurgical oncology patients, due to the difficult balance of achieving effective VTE prophylaxis without raising the risk of hemorrhages that result in neurological deficits. The current standard for VTE prophylaxis is based on published 2007 American Society of Clinical Oncology (ASCO) guidelines for VTE prevention—but it does not adequately address the benefits and unique risks encountered in the neurosurgical oncology procedures [3]. The ASCO guidelines recommend: “All patients undergoing major surgical intervention for malignant disease should be considered for thromboprophylaxis” [3]. Pre-operative or early postoperative pharmacologic prophylaxis with unfractionated heparin (UFH) or low molecular weight heparin (LMWH) is recommended for laparotomy, laparoscopy, or thoracotomy lasting longer than 30 min. It is also specified that sequential compression devices should not be used alone as prophylaxis unless a patient is at high risk for bleeding [3]. Without qualification, the ASCO guidelines state: “Prophylaxis should be commenced preoperatively, or as early as possible in the postoperative period” [3]. Regarding the neurosurgical population, the ASCO guidelines reference a 1998 study of Agnelli et al. support chemical prophylaxis with LMWH initiated within the first 24 h postoperatively in addition to mechanical prophylaxis for VTE reduction [4]. In addition, a metaanalysis from 2008 CHEST focusing on VTE in neurosurgical patients suggested that mechanical or chemical prophylaxis alone decreases VTE risk; however, high risk populations such as cancer patients may benefit from using both mechanical and chemical prophylaxis therapies [5]. In a recently published meta-analysis of randomized clinical trials utilizing heparin VTE prophylaxis in elective craniotomies, a higher hemorrhagic incidence was found in heparinized (UFH

Posterior Circulation Aneurysms: Clip or Coil?

Posterior circulation aneurysms include aneurysms of the vertebral artery (VA), vertebrobasilar (VB) junction, basilar bifurcation, posterior inferior cerebellar artery (PICA), anterior inferior cerebellar artery (AICA), superior cerebellar artery (SCA) and posterior cerebral artery (PCA). They differ from their anterior circulation counterparts because of their less accessible deep locations and propensity for complex morphology.