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Earlier observers have speculated on the causal relationships between abnormal CSF circulation and a variety of neurological dysfunctions. Such speculations have been at least partially validated by recent evidence and inquiries contravening the traditional static viewpoint of CSF circulation. More contemporary inquiries establish a number of factors which influence both CSF production and absorption (sleep disturbance, neck position, cerebral metabolism, brain atrophy, medications, etc.). Thus, transient periods of abnormality are possibly mingled with periods of normality. Such episodic alterations suggest that the physiological arrangements which underpin CSF circulation may be in some ways likened to blood pressure alterations, in that long-standing CSF abnormalities may be both unappreciated and gradual, though virulent enough to cause substantial neurological injury. We suggest that cervical stenosis (blocking an important CSF decompressive pathway into the vertebral canal) is among the largely unappreciated causes of abnormal CSF circulation and may play a role in cephalad neuronal dysfunction. Such a blockage is correlated with age and easily assessed by cine MRI study. Indeed, episodic disturbances can diminish CSF cerebral flow circulation increasing deposition in cerebral parenchyma of contrary metabolic products (e.g. beta Amyloid), possibly having a causal influence on senile dementia. Additionally, cervical stenosis, by increasing posterior fossa cerebral pressure, could play a causal role in a number of afflictions, among them sleep apnea, concomitant respiratory and circulatory dysfunction, hypertension, chronic occipital headaches, tinnitus, etc. We further suggest that among those patients with substantial cervical stenosis (extensive enough to block CSF circulation in the cervical area as identified by cine MRI) appropriate comparative clinical studies could be undertaken to demarcate associations with presenile dementia, sleep disturbance and posterior fossa dysfunction. Additionally, we suggest that an intracranial monitoring implant be perfected to chronically monitor both intracranial pressure and CSF flow - a monitoring device comparable to the rather less invasive sphygmometric evaluation of blood pressure. If such speculations prove correct, different therapeutic regimens which might improve outcome could be imagined. Among them better sleep hygiene (to by position maximize CSF flow) and possibly more aggressive operative decompressive intervention to diminish cervical obstruction.

Objectives: To extract from germane literature methodological shortfalls in obtaining cerebrospinal fluid specimens by lumbar puncture. Methods: 20 peer reviewed articles were analyzed in which cerebrospinal fluid (CSF) obtained biomarkers were used to assess Alzheimer’s Disease. Binary assessment of eight variables was performed: albumin, total protein, CSF pressure, cephalad CSF obstruction, obtained but unreported data, inclusion of erythrocyte contaminated samples, exclusion of erythrocyte contaminated samples, exclusion of white blood cell contaminated samples, and failed lumbar puncture attempts. Results: An apparent shortfall exists in the assessment of contravening variables, which could alter CSF results. Conclusions: We suggest that more attention be placed on lumbar puncture methodological difficulties in obtained CSF specimens, and that all practical obtainable data be routinely reported.

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INTRODUCTION Despite some evidence that anxiety may affect length of stay (LOS), relatively little inquiry exists regarding this in neurosurgical literature. OBJECTIVE To determine the influence of anxiety on LOS after elective lumbar decompression and fusion (LDF) surgery. METHODS The medical records of 307 patients who consecutively underwent elective LDF surgery from October 1, 2010, through September 30, 2013, were retrospectively reviewed. Each patient's medications and comorbidities were determined using the medical history. The impact of their medications on LOS was studied using multivariate analysis. Linear regression was also used to assess the relationship between anxiolytic use and LOS. An independent sample t test was used to compare the mean LOS of the group of patients receiving muscle relaxants with that of the group who were not. RESULTS Those with a diagnosis of anxiety who were taking anxiolytics (n = 32) stayed 1.8 days longer than those with no diagnosis of anxiety and who were not taking anxiolytics (n = 224) after LDF surgery (p = 0.003). Those with a diagnosis of anxiety who were taking anxiolytics (n = 32) stayed 1.9 days longer than those with no diagnosis of anxiety and who were taking anxiolytics (n = 24) after LDF surgery (p = 0.003). CONCLUSION Our study suggests that those with a diagnosis of anxiety who take medications for that condition have a longer LOS than those with no diagnosis of anxiety and who are not medicated for the condition. This could be because these patients are more vulnerable to states of anxiety when required to be nil per os for 12 hours before surgery.

Introduction: In this paper we investigate the possible connection between socioeconomic status as demarcated by employment and in-surance status and consumption of healthcare resources in spine surgery patients. Methods: The clinical records of 1599 spine surgery pa-tients counted from 2008-2009 were reviewed. The largest groups of patients belonged to MS-DRG 460 (N = 585) and to MS-DRG 473 (N = 700). These two MS-DRG patient groups were used as the study cohort representing patients who, by definition, did not have serious comor-bidities or complications. Results: Unemployed non-cervical patients tended to stay on average 1.8 days longer in hospital and had on average $5800 higher hospital charges. No major differ-ences were noted in length of stay and hospital cost between government and private insurance patients. However, self-pay non-cervical fusion patients had notable increases in length of stay and hospital cost, especially in the >39 and

Introduction. Aggressive surgical resection constitutes the optimal treatment for intracranial gliomas. However, the proximity of a tumor to eloquent areas requires exact knowledge of its anatomic relationships to functional cortex. The purpose of our study was to evaluate fMRI’s accuracy by comparing it to intraoperative cortical stimulation (DCS) mapping.Material and Methods. Eighty-seven patients, with presumed glioma diagnosis, underwent preoperative fMRI and intraoperative DCS for cortical mapping during tumor resection. Findings of fMRI and DCS were considered concordant if the identified cortical centers were less than 5 mm apart. Pre and postoperative Karnofsky Performance Scale and Spitzer scores were recorded. A postoperative MRI was obtained for assessing the extent of resection.Results. The areas of interest were identified by fMRI and DCS in all participants. The concordance between fMRI and DCS was 91.9% regarding sensory-motor cortex, 100% for visual cortex, and 85.4% for language. Data analysis showed that patients with better functional condition demonstrated higher concordance rates, while there also was a weak association between tumor grade and concordance rate. The mean extent of tumor resection was 96.7%.Conclusions. Functional MRI is a highly accurate preoperative methodology for sensory-motor mapping. However, in language mapping, DCS remains necessary for accurate localization.

Introduction: Health care expenditures in the United States have rapidly risen in the last decade, including orthopaedic induced expenses. This paper addresses the methodology by which clinical evidence is obtained to better direct orthopaedic practice and encourage cost-efficiency. Questions: We conducted this inquiry to answer these questions: 1) Have orthopaedic expenses increased in the United States? 2) Does high grade clinical evidence prevail in orthopaedic literature? 3) Does clinical orthopaedic research include cost in outcome analysis? 4) Does the increase in orthopaedic expenses correlate with cost awareness in orthopaedic literature? Methods: The aggregate hospital charges (national bill) associated with three major orthopaedic procedures were extracted from the Nationwide Inpatient Sample (NIS) website (data available from 1997 to 2008). Using the biomedical search engine PubMed (launched 1996), different types of literature pertaining to general orthopaedic and three major orthopaedic procedures—hip replacement, knee replacement, and spine fusion, were probed regarding level of evidence and cost inclusion. Results: From 1997 to 2008, the national hospital charges for spine fusion increased by 10.4 times while for total knee replacement it increased by 4.9 times and for total/partial hip replacement by 3.4 times. From 1996 to 2010, PubMed indexed 1113 randomized controlled trials (RCTs) related to hip replacement, 942 related to knee replacement and 357 related to spine fusion. During the same period, RCTs related to total/partial hip replacement, total knee replacement and spine fusion procedures have increased by 3 times, 6 times, and 3.4 times, respectively. The percentage of blinded RCTS with cost analysis among all RCTs related to each procedure were 0%, 0.001% and 0.003% for total/partial hip replacement, total knee replacement and spine fusion procedures respectively. The correlation in the national hospital charges of all three procedures individually and their level I literature with cost element was not significant except for spine fusion. Conclusion: To improve literature shortfalls, substantial attention needs to be focused toward more rigorous studies which consider cost efficiency.

Interleukin-lβ (IL-lβ) is associated with vascular smooth muscle cell (VSMC) migration during neointimal formation following arterial injury, of which matrix metalloproteinase-2 (MMP-2) may have an important role. We investigated whether IL-lβ stimulated migration and MMP-2 production in VSMC, and, if so, whether migration correlated with MMP-2 activity.Modified Boyden chamber assay quantified cultured rat aorta VSMC migration. Methyl-thiazolyl-tetrazolium assay assessed cell growth. Gelatin zymography and Western blotting determined MMP-2 activity and protein levels, respectively.IL-lβ (0.1 - 10 ng/mL) induced migration of VSMC in a concentration-dependent manner without cell proliferation. VSMC released increasing levels of active MMP-2 in a dose-response fashion at IL-1β 1-10 ng/mL (P0.05) while significantly increased levels of latent MMP-2 (pro-MMP-2) were attained more gradually (10 ng/mL, P0.05). There was a dose-dependent increase in the ratio of active MMP-2 to pro-MMP-2 in response to IL-1β (1-10 ng/mL, P0.05), suggesting extracellular activation of pro-MMP-2. Protein levels on Western blot paralleled enzyme activity, with the synthesis of more active MMP-2 than pro-MMP-2 in response to IL-1β. IL-lβ-stimulated VSMC migration was significantly attenuated by both the pan-selective MMP inhibitor GM6001 and cis-9-octadecenoyl-N-hydroxylamide, a MMP-2-selective inhibitor.IL-lβ increases MMP-2 activity in VSMC through increased protein synthesis and activation of pro-MMP-2. VSMC migration induced by IL-lβ requires active MMP-2. IL-lβ may play a role in arterial remodeling following injury.

Chronic back pain is commonly associated with physical and mental comorbidities, which create a considerable burden on the healthcare system. We examined the differences in comorbidity rates of 619 spinal surgery patients of employment age, and the impact of comorbidity rates on length of hospital stay and cost. The charts of patients aged >25 years and

Complex shifts in demography combined with drastic advancements in spinal surgery have led to a steep increase in often expensive spinal interventions in older and obese patients. A cost analysis, based on hospital charges, was performed retrospectively on the spinal surgery of 787 randomly selected patients who were operated at The Medical Center of Central Georgia, a large urban hospital in Central Georgia. The types of surgery included anterior cervical decompression and fusion (ACDF), lumbar decompression and fusion (LDF), and lumbar microdiscectomy (LMD). The distribution of patient age followed a Gaussian form. The peak age for patients was 50–59 years (28.8%), and there was no statistical difference in age between men and women. The body mass index (BMI) differed ( p 2 ; range: 18–47 kg/m 2 ) and females (30.69 kg/m 2 ; range: 17–58 kg/m 2 ). The BMI data did not follow a Gaussian distribution for either gender. The hospital cost for spinal surgery increased with age except for male patients who underwent ACDF. For male patients who underwent LDF, the increase in hospital cost was statistically significant between the 40–49-year and the ⩾70-year age groups. Univariate analysis with type of surgery as a covariate showed that age was a significant determinant of hospital cost ( p = 0.000), and BMI was not ( p = 0.110); however, the interaction between age and BMI was significant ( p = 0.000). Older patients undergoing spinal surgery had lower BMI, more so in males ( r = −0.047, p = 0.426) than in females ( r = −0.038, p = 0.485). There were linear trends in all gender–spinal surgery categories between age, BMI and hospital cost. Older female patients who underwent LDF tended to have a lower BMI but higher hospital cost, confirming that age was more important than BMI in determining hospital cost in these patients. The increments in cost of spinal surgery in relation to age especially and BMI were, nevertheless, small. We believe that spinal surgery in the elderly should be viewed as a public investment, as the modern concept of retirement involves people working intermittently up to their 80s. Thus, where clinical research on medical costs is to be conducted, cost analysis needs to be expanded to include returns to government in the form of taxes.

Object Comorbidities in patients undergoing spine surgery may reasonably be factors that increase health care costs. To verify this hypothesis, the authors conducted the following study. Methods Major comorbidities and age-adjusted Charlson Comorbidity Index scores were retrospectively analyzed for 816 patients who underwent spine surgery at the authors' institutions between 2005 and 2008, and treatment costs (hospital charges) were assessed with the help of statistical software. The sample was collected by a nonmedical staff (hired at the beginning of 2006). Patients underwent one of the three most common types of spine surgery: lumbar microdiscectomy (20.5%), anterior cervical decompression and fusion (ACDF; 60.3%), or lumbar decompression and fusion (LDF; 19.2%). Patients were nearly equally divided by sex (53% were female and 47% male), and 78% were Caucasian versus 21% who were African American; the rest were of mixed or unidentified race. The average age was 54 years, with an SD of ± 14 years. Results There were significant differences in the prevalence of major comorbidities between male and female and between severely obese and nonseverely obese patients. The impact of comorbidities on the cost of spine surgery was more prominent in older patients, and an additive effect from some comorbidities was recorded in various types of spine surgery. For instance, in the ACDF group, female patients with both severe obesity and diabetes mellitus (DM) had significantly higher hospital charges than those with only one or neither of these conditions ($34,943 for both severe obesity and DM vs $25,633 for severe obesity only; $25,826 for DM only; and $25,153 for those with neither condition [p < 0.05]). In the LDF group, female patients with both DM and a history of depression had significantly higher hospital charges than those with only one or neither of these conditions ($65,782 for both DM and depression vs $53,504 for DM only; $55,990 for depression only; and $52,249 for those with neither condition [p < 0.05]). A significant difference was also found in hospital cost ($16,472 [p < 0.01]; 32% increase over baseline) in the LDF group between patients with the lowest and highest scores on the Charlson Index. Conclusions Comorbidities additively increase hospital costs for patients who undergo spine surgery, and should be considered in payment arrangements.

Introduction Vitamin B12 is very vital for the nervous system. Its deficiency can manifest with neurological symptoms like pain and paresthesias and in severe cases may cause not completely restorable neurological damage, especially in elderly patients. Methods The charts of 702 patients who underwent cervical spine surgery retrospectively reviewed and data collected . All patients were preoperatively seen by an internist who ordered Vit B12 levels for some of them. We used two thresholds for the diagnosis of vitamin B12 deficiency, 200 and 300 pg/mL as recommended by Yao et al. 1992. Data were also collected on gender, payor status, myelopathy, hemoglobin level, corpuscular parameters and glycosylated hemoglobin level (HbA1c). Vitamin B12 levels were compared between patients with HbA1c levels ≥ 6.1% and

Clinical information suggests that opioid dependence is a major contributor to poor outcomes involving health status and to increased length of stay in hospital settings. Before spine surgery, 150 patients who were using an opioid medication for pain relief were interviewed using the six World Health Organization (WHO) guidelines for the diagnosis of opioid dependence. Three groups were defined: opioid-dependent, nonopioid-dependent, and a subclinical group. Results revealed an average of 20% of patients ( N = 30) who met the WHO criteria for the diagnosis of opioid dependence. There were significant positive correlations between age and number of positive WHO criteria, length of stay, and time under surgery. Length of stay was significantly higher for the older age group (> 55 yr.). ANCOVA analysis using two opioid dependence groups (+ and -) and age group as independent variables affecting length of stay, after controlling for type of surgery, pain intensity, and number of previous spine surgeries, revealed that effects of opioid dependence status and age were significant but their interaction was not. Age did add length of stay independently of opioid dependence status; older adults remain in the hospital longer for various reasons probably associated with comorbidities.

Background context Somatosensory evoked potential (SSEP) is used to monitor integrity of the brain, spinal cord, and nerve roots during spinal surgery. It records the electrical potentials from the scalp after electrical stimulation of the peripheral nerves of the upper or lower limbs. The standard monitoring modality in lumbosacral spine surgery includes lower-limb SSEP and electromyography (EMG). Upper-limb SSEP monitoring has also been used to detect and prevent brachial plexopathy and peripheral nerve injury in thoracic and lumbosacral spine surgeries. We routinely monitor lower-limb SSEP and EMG in lumbosacral spine procedures at our institution. However, a few patients experienced postoperative numbness and/or pain in their ulnar distribution with uneventful lower-limb SSEP and EMG. Purpose We hypothesized that the postoperative upper extremity paresis in lumbosacral surgeries may result from compression and/or stretch of the brachial plexus and/or ulnar nerve while the patients were in prone position. Using upper-limb SSEP, we investigated whether we observe any significant change in the SSEP, and if so, whether we can prevent or reduce frequency of postoperative upper extremity deficits. Study design/setting In this prospective study, we monitored upper-limb SSEP, in addition to lower-limb SSEP and EMG, in 230 elective, posterior lumbosacral spinal procedures. All operations were performed by a group of four neurosurgeons. Patient sample One hundred and thirty-one female and 99 male with an age range of 28 to 86 years between January 2004 and December 2005 were studied. Outcome measures Amplitude and latency of upper-limb or ulnar SSEP were continuously compared with those of the baseline. A greater than or equal to 50% decrease in SSEPs amplitude and/or a greater than or equal to 10% increase in latency were considered to be significant. Methods After intubation, patients were positioned prone on Jackson or Andrews spinal table. Anesthesia was maintained with inhalant gas (desflurane or sevoflurane) and propofol infusion with and without minimal infusion of narcotics (fentanyl, sufentanyl, or remifentanil). Intraoperative neurophysiologic monitoring of upper-limb or ulnar SSEP was achieved by continuously recording cortical and subcortical responses after alternate stimulation of the ulnar nerve at the wrist. In our institutional protocol, a greater than or equal to 50% decrease in SSEPs amplitude and/or a greater than or equal to 10% increase in latency were considered to be significant to alert the operating surgeons. When significant changes occurred, the surgeon was immediately notified. Also, reevaluation of vital signs, depth of anesthesia, and patient's position, and technical troubleshootings were subsequently followed. Results We observed a greater than or equal to 50% decrease in amplitude of ulnar SSEP in 10 patients without significant changes in lower-limb SSEP (peroneal or posterior tibial nerve SSEP) or EMG during surgery. Eight patients had changes in unilateral limbs, and two patients had changes in bilateral limbs. Two patients with significant changes in unilateral limbs showed changes twice. The mean SSEP amplitude for the 14 changes was 29.2±3.1% (mean±SEM, standard error of mean) of the baseline value at the average surgical time of 60±1.5 minutes. With repositioning of the arms, the amplitudes were immediately restored with the average of 70.2±7.1% (n=14) of the baseline value. The mean amplitude of upper-limb SSEP was 73.4±8.7% (n=12) of the baseline at wound closure. The average surgical time was 154±29.2 minutes per case for the 10 patients. There was no documented postoperative upper extremity paresis in all 230 patients. Conclusions The present study demonstrates that upper-limb SSEP monitoring could detect position-related ulnar neuropathy in 5.2% of the patients undergoing lumbosacral spine surgery.

Study design Prospective, clinical study. Objective The objective of our study was to evaluate the role of laryngeal intraoperative electromyography (IEMG) in predicting the development of postoperative recurrent laryngeal nerve (RLN) palsy in patients undergoing anterior cervical discectomy and fusion (ACDF). We also attempted to develop a method to quantify the total IEMG irritation of the RLN. Summary of background data RLN injury has been recognized as the most common ACDF-associated neurologic injury. It has been postulated, that the employment of laryngeal IEMG may identify the operative events leading to RLN injury and subsequent postoperative palsy. Methods Laryngeal IEMG monitoring was performed in 298 patients undergoing ACDF. Preexistent baseline EMG activity, amplitude, and duration of IEMG activity were recorded. The total amount of RLN irritation was expressed as an Irritation Score (IS) applying a specially designed mathematical equation incorporating the amplitude, the duration, and the presence of any baseline EMG irritation. The relationship of IEMG activity with parameters such as the number of operative levels, the duration of the procedure, the presence of any previous neck surgeries, and the type of the used retractor was examined. Results IEMG activity was recorded in 14.4% of our patients. Postoperative RLN injury occurred in 2.3% of our patients. The sensitivity of IEMG was 100%, the specificity 87%, the positive predictive value 16%, and its negative predictive value 97%. The calculated IS ranged between 0.28 and 3.47 (mean IS: 2.09). Significantly increased IEMG activity was found in patients with previous surgical intervention, patients undergoing multilevel procedures, long-lasting procedures, and cases in which self-retained retractors were used. Likewise, significantly increased IS were observed in patients with previous surgeries and in cases where self-retained retractors were used. Conclusions Our study indicates that laryngeal IEMG is a high-sensitivity modality that can provide real-time information and can potentially minimize the risk of operative RLN injury.

Acute pain is reported as a presenting symptom in over 80% of physician visits. Chronic pain affects an estimated 76.2 million Americans--more than diabetes, heart disease, and cancer combined. It has been estimated to be undertreated in up to 80% of patients in some settings. Pain costs the American public more than $100 billion each year in health care, compensation, and litigation. That's why pain was officially declared "The Fifth Vital Sign." Henceforth the evaluation of pain became a requirement of proper patient care as important and basic as the assessment and management of temperature, blood pressure, respiratory rate, and heart rate. The numeric pain scale certainly has a place in care and in pain management; however, it is important to assess the patient's communication and self-management style and to recognize that patients, like pain, are on a continuum with varied styles of communication and adaptation. It is easy to get lost in the process, even when the process is initiated with the best of intentions. In the quest for individualized medicine, it might be best to keep pain assessment in the individualization arena.

Object The association of vitreous and/or subhyaloid hemorrhage with aneurysmal subarachnoid hemorrhage (SAH) has been frequently identified since the original description by Terson in 1900. In this prospective clinical study the authors examined the actual incidence of Terson hemorrhage in patients suffering aneurysmal SAH, they attempted to identify those parameters that could predispose its development, and they evaluated its prognostic significance in the overall patients' outcome. Methods A total of 174 patients suffering aneurysmal SAH were included in this study. The admitting Glasgow Coma Scale scores (GCS), World Federation of Neurological Societies (WFNS) scale scores, Hunt and Hess grades, and Fisher grades were recorded. A careful ophthalmological evaluation was performed in all participants. The exact anatomical locations and the largest diameter of the dome of the ruptured aneurysms were also recorded. Surgical clipping or endovascular coiling was used in 165 patients. Clinical outcome was evaluated at discharge from the hospital by using the Glasgow Outcome Scale and the modified Rankin Scale. Periodic ophthalmological evaluations were performed for 2 years. Results In this series, the observed incidence of Terson hemorrhage was 12.1%. Statistical analysis of our data demonstrated that patients with low GCS scores and high WFNS scores, Hunt and Hess grades, and Fisher grades had an increased incidence of Terson hemorrhage. The mortality rate for patients with Terson hemorrhage was 28.6%, whereas that for patients without Terson hemorrhage was 2.0%. Moreover, patients with Terson hemorrhage who survived had significantly worse outcomes than those in patients without Terson hemorrhage. Conclusions Terson hemorrhage constitutes a common SAH-associated complication. Its incidence is increased in patients with low GCS and high WFNS scores, and high Hunt and Hess and Fisher grades. Its presence is associated with increased mortality and morbidity rates.

The purpose of our current study is to describe the guidelines regarding trephination as suggested in the Hippocratic writer's book, "Peri ton en cephali traumaton" ("On Head Wounds"). The ancient Greek text was reviewed as well as two English translations. The Hippocratic author described the indications, timing, and techniques of trephination for patients with head injury. He emphasized that attention should be paid to the details of the employed technique. He also commented on the difference of skull thickness at different anatomical sites and also between different age groups. The Hippocratic recommendations provided details for the performance of trephination by the ancient Greek physicians that are still considered important in modern neurosurgery.

We present the results of a retrospective study employing intraoperative micro-Doppler ultrasonography (MDU) in verifying proper clip placement during cerebral aneurysmal surgery. One hundred and thirty-four patients surgically treated for 147 intracranial aneurysms were studied. Thirteen patients harboring 17 aneurysms were surgically treated on an elective basis, while 121 patients with 130 aneurysms, presented with subarachnoid hemorrhage (SAH). Blood flow velocities of the parent and adjacent vessels as well as the aneurysmal sac were measured using a Conforma Micro-Doppler (Cook Vascular Inc., Leechburg, PA, USA). Pre- and post-operative cerebral angiography was obtained in all our patients. In 23 aneurysms (15.6%) there was decreased or absent flow in the parent vessel or in one of the adjacent vessels after clipping. In another 19 aneurysms (12.9%), MDU demonstrated flow through the aneurysmal dome even though the aneurysmal neck appeared to be totally obliterated. Presence of SAH, anatomic location and size of the aneurysm were associated with improper clip placement in a statistically significant fashion. The false positive rate for MDU was 2% while there were no false negative findings in our study. MDU appears to be a non-invasive, reliable alternative methodology to intra-operative angiography. This inexpensive method may lend itself to routine usage in aneurysm surgery.

Objective: This study describes a single-site investigation on the effects of a randomized double-blind placebo trial targeting duloxetine added to opioid use (duloxetine + opioid) against a comparator (placebo + opioid) in spine surgery patients, independent of major depression. Design: The double-blind comparator study assessed two groups on opioids: one using duloxetine and the other a placebo. Subjects were administered the respective medication 2 weeks prior to surgery and continued on this for more than 3 months. Subjects were assessed at three times: prior to surgery, 4 weeks postsurgery, and 12 weeks postsurgery. They completed a battery of tests assessing for pain, adjustment, and psychiatric problems. Setting: Neurosurgical outpatient and inpatient setting. Patients: Sixty-eight patients completed the study. They received one of three types of elective spine surgery. Interventions: Subjects were given duloxetine or placebo 2 weeks prior to surgery and continued with the regimen for more than 3 months. Outcomes: The primary focus was pain and second on adjustment factors and psychiatric symptoms: depression and anxiety. The amount of opioid use presurgery and postsurgery was also evaluated. Results: There were differences among the groups on Brief Pain Inventory (BPI)-Average, the core pain marker, and BPI-Sleep. Within-subject analyses showed that duloxetine subjects improved significantly from baseline. For function, post-CIBIC and post-Functional Adjustment Questionnaire were significant, favoring duloxetine. Reduction of opioid use was not a factor; both groups' utilization declined. For affect, both groups were significantly improved over time. Conclusions: Duloxetine seems to improve pain, assist with maintaining function, and reduce intensity of affect.

Gastrointestinal Preparation May Reduce Length of Stay in Spine Surgery: Quality Improvement Project In a healthcare system troubled by escalating demands escalating costs, the last decade has seen a marked increase in both volume and cost of surgical spine procedures. Probing methodologies to reduce such costs without jeopardizing patient outcome would generate substantial benefit. This paper assesses the effect of administering milk of magnesia (MOM) for bowel preparation on the length of hospital stay (LOS).

Traumatic epidural hematoma (EDH) represents a rare head injury complication in infants. Its diagnosis can be quite challenging because its clinical presentation is usually subtle and nonspecific. In our current communication, we present our data regarding the presentation of infants with EDH, their management, and their long-term outcome. In a retrospective study, the hospital and outpatient clinic charts and imaging studies (head CT and skull X-rays) of 31 infants with pure, supratentorial EDH of traumatic origin were meticulously reviewed. Children Coma Scale score and Trauma Infant Neurologic Score (TINS) were also reviewed. The most common presenting symptom was irritability, which occurred in 18/31 (58.1%) of our patients. Pallor (in 30/31 patients) and cephalhematoma (in 21/31 patients) were the most commonly occurring clinical signs upon admission; both signs represent signs of significant clinical importance. Surgical evacuation via a craniotomy was required in 24/31 of our patients, while 7/31 patients were managed conservatively. The mortality rate in our series was 6.5% (2/31 patients), and our long-term morbidity rate was 3.2% (1/31 patients). EDH in infants represents a life-threatening complication of head injury, which requires early identification and prompt surgical or conservative management depending on the patient’s clinical condition, size of EDH, and presence of midline structure shift on head CT scan. Mortality and long-term morbidity are low with early diagnosis and prompt treatment.

The fusion rate represents one of the most commonly used criteria for evaluating the efficacy of spinal surgical techniques and the effectiveness of newly developed instrumentation and spinal implants. Reported fusion rates are not frequently supported by adequate information regarding by whom and how fusion was defined. In our prospective study we examined the fusion rate in patients undergoing first time anterior cervical discectomy and fusion for degenerative disease. Separate, well-defined radiographic fusion criteria were used and the 12-month post-operative X-rays were reviewed independently by a neurosurgeon, a neuroradiologist and an orthopedic surgeon, who were not involved in the patients' management. The observed fusion rates were 77.3, 87.8 and 84.7% respectively. Statistical analysis demonstrated concordance rates of 87.8, 91 and 91.4% and Kappa coefficients of 0.585, 0.620 and 0.723 for each pair of evaluators. Another set of ratings of the same radiographs, by the same interviewers, was obtained 6 weeks after the initial one. The reported fusion rates were 78.2% for the neurosurgeon, 87.4% for the orthopedic surgeon, and 86.1% for the neuroradiologist. Statistical analysis demonstrated intra-observer concordance rates of 98.7, 92.2 and 97.9% respectively, while the Kappa coefficients were 0.963, 0.677 and 0.907 for each reviewer. Our findings confirm the necessity of defining and describing criteria for fusion whenever this rate is reported in clinical series. The lack of widely accepted, well-defined criteria makes comparison of these results difficult. The development of a well organized, prospective clinical study in which fusion and outcome will be assessed by both clinical and radiographic parameters could significantly contribute to a more accurate evaluation of overall outcome of cervical spinal procedures.

An ultrasonic method was used to non-invasively measure intracranial blood volume (IBV) pulse waveforms. This technology has previously shown a strong association between invasively recorded ICP pulse waves and non-invasively recorded IBV pulse waves. The objective of the present study was to investigate the diagnostic value of non-invasively measured IBV pulse waves in the cases of different pathologies. A total of 75 patients were examined and these included cases of acute, chronic and stabilized hydrocephalus, spinal cord injury and terminal blood flow. These were compared to a control group of 53 healthy volunteers. The object of comparison was normalized and averaged IBV pulse waves. Pathological IBV pulse waveforms were compared with IBV pulse waveforms of the normal group using sub-wave values, the area under waveform curve and the Euclidean distance calculation. The non-invasively measured IBV pulse waveform is not significantly dependent on acoustic path, gender or age. A detectable change in IBV pulse waveform shape was observed in situations when disturbance in intracranial hydrodynamics was present, e.g. during hypoventilation tests, in cases of terminal blood flow and hydrocephaly, depicting the level of hydrocephalus activity and the patient's compensatory capabilities as well as the effect of treatment.

Acute hydrocephalus is a well-documented complication of subarachnoid hemorrhage. The insertion of external ventricular drainage (EVD) has been the standard of care in the management of this complication, aiming primarily at immediate improvement of the clinical condition of these patients, making them more suitable candidates for surgical or endovascular intervention. In our current communication, we review the pertinent literature regarding the relationship of rebleeding and EVD. Several studies have implicated a significantly increased risk of rebleeding in patients with EVD, compared with patients without it. Abrupt lowering of the intracranial pressure could lead to rebleeding due to decreased transmural pressure or removal of the clot sealing the previously ruptured aneurysm. However, a variety of parameters that could affect the rebleeding rate, such as the timing of surgery, the timing and duration of drainage, the size of the aneurysm, as well as the severity of the initial hemorrhage, do not seem to have been adequately explored in the majority of these studies. In addition, a number of clinical trials have failed to provide evidence for the negative role of EVD in the development of rebleeding. Conclusively, further long-term multi-center studies are required in order to establish the exact nature of the relationship between EVD and rebleeding after aneurysmal subarachnoid hemorrhage.

The association of third cranial nerve palsy subsequent to an enlarging posterior communicating artery (P-Com A) aneurysm has been well described. In our current communication, we review the relevant literature and propose a classification system for the severity of the third cranial nerve palsy, correlating it to the postoperative recovery. Our four grade scale (I-IV) included the degree of the levator palpebrae muscle paresis, the presence of pupillary reaction and the impairment of the third nerve mediated extraocular muscle movement. We evaluated five patients with third nerve palsy secondary to non-ruptured, P-Com A aneurysm. Patients were re-evaluated at 2, 4, 8, 24 weeks postoperatively. Four of the five patients had complete recovery within 4-8 weeks after surgery. One patient had grade II third nerve paresis and complete resolution of the third nerve symptoms within 4 weeks, whereas three patients with grade III and IV had complete resolution 4-8 weeks after surgery. The fifth patient, with grade IV paresis, had minimal (grade III) improvement 6 weeks after surgery, and incomplete recovery (grade I) 6 months postoperatively. Our simple grading system of third nerve palsy associated with P-Com A aneurysms, can be a helpful tool for the initial evaluation and for the monitoring of recovery in these patients.

The purpose of this article is to provide insight into the development of surgery for acoustic neurinomas throughout the years. The significant contribution of surgical authorities such as Cushing, Dandy, and House are discussed. The advances in surgical techniques from the very first operations for acoustic tumors at the end of the 19th century until today are described, with special emphasis on the technological and diagnostic milestones that preceded each step of this development.

Study design Retrospective analysis of the fusion rate of a group of 38 patients having undergone anterior screw fixation for type II and "shallow" type III odontoid fractures. OBJECTIVE.: To determine primarily the long-term fusion rate after anterior screw fixation and to study the clinical characteristics of patients that have a statistically significant or nonsignificant influence on successful outcome. Summary of background data Long-term outcome of anterior screw fixation for odontoid fractures has been evaluated in very few studies. This information should be critical for further establishing this technique as a major therapeutic strategy for these cases. Methods Thirty-eight patients, 25 males and 13 females (with mean age 48.4 +/- 0.4 years), with type II and rostral type III odontoid fractures, underwent anterior cannulated screw fixation during a 62-month period. Radiologic examination of the cervical spine with plain radiographs was performed at 6 weeks, and 2, 6, 12, and 24 months, while computerized tomography of the upper cervical spine (C1-C3) was obtained at 6 months after surgery. Follow-up was available for 31 patients, and the follow-up time ranged from 39 to 87 months (mean 58.4). Results Radiographic evaluation of the follow-up group showed satisfactory bony fusion and no evidence of abnormal movement at the fracture site in 27 (87.1%) patients. Pseudarthrosis developed in 4 (12.9%) patients; however, 3 (9.6%) of them without instability and 1 (3.2%) with instability. One (3.2%) patient had an instrumentation failure without instability. Conclusions In our series, anterior odontoid screw fixation comprised a safe therapeutic modality with high stability and low mechanical failure rates during short-term and long-term follow-up.

OBJECTIVES The atlantoaxial segment of the cervical spine is commonly destabilized in a variety of disorders. Transarticular screw fixation of the C1-C2 joint has been proposed as a biomechanically superior therapeutic modality. The authors present their experience with this technique. METHODS A retrospective analysis of 23 patients treated with this technique was performed. The mean follow-up period was 39.5 +/- 0.1 months. RESULTS Mean duration of hospitalization was 3.4 +/- 0.1 days (range, 2 to 11 days). No intraoperative or early postoperative complications were detected. Four patients (17.4%) had postoperative complications unrelated to the primary procedure. The position of the screw was judged as satisfactory in 21 patients (91.3%). Two patients (8.7%) with suboptimal positioning of the screws were neurologically intact but needed no reoperation. Solid osseous fusion was detected in 19 patients (82.6%). CONCLUSIONS Transarticular C1-C2 screw fixation appears to be a safe and surgically reliable technique. Criteria for its application and refinements in its technical considerations continue to advance its clinically versatile therapeutic potential.

The authors offer a brief overview of early theories and treatments of sciatica. Tracing medical traditions through early Greek, Roman, and Eastern epochs, the authors demonstrate the slow sequential steps that were required to delineate this disease as a uniquely human affliction.

This case report presents a newborn baby girl, who was diagnosed at birth with a mid-cervical meningocele. Further radiographic workup by MRI revealed co-existing thoracic diplomyelia and bilateral tethered cords. At birth the patient was found to be neurologically intact. Surgery was performed at 4 months of age, the patient undergoing simultaneous repair of the cervical meningocele, exploration of the diplomyelia, and release of the tethered cords bilaterally. Long-term follow-up revealed an ambulating patient with no bowel or bladder incontinence, who has developed well for her chronological age so far.A review of the literature relevant to this case is also presented.

Introduction: The wide use of intracranial pressure and cerebral perfusion pressure monitoring has improved the management of patients with severe head injuries. The rare but worrying complications associated with the application of such monitoring makes the idea of a non-invasive method of monitoring very attractive. Materials and methods: A new non-invasive ultrasonographic technology was used to measure cerebral perfusion pressure in 27 normal volunteers. The average monitoring time was 45.3±0.2 min, and the average perfusion pressure recorded was 77.4±0.3 mmHg. No complications were reported during the procedure, which was performed while the subjects were in regular ward beds. Conclusion: The non-invasive character of this method could extend the use of cerebral perfusion pressure measurement to several other neurosurgical entities, such as hydrocephalus, pseudotumor cerebri, chronic headache, and spinal cord injuries.

Raman spectroscopy has recently been applied ex vivo and in vivo to address various biomedical issues such as the early detection of cancers, monitoring of the effect of various agents on the skin, determination of atherosclerotic plaque composition, and rapid identification of pathogenic microorganisms. This leap in the number of applications and the number of groups active in this field has been facilitated by several technological advancements in lasers, CCD detectors, and fiber-optic probes. However, most of the studies are still at the proof of concept stage. We present a discussion on the status of the field today, as well as the problems and issues that still need to be resolved to bring this technology to hospital settings (i.e., the medical laboratory, surgical suites, or clinics). Taken from the viewpoint of clinicians and medical analysts, the potential of Raman spectroscopic techniques as new tools for biomedical applications is discussed and a path is proposed for the clinical implementation of these techniques.

Brain edema is one of the most common morbidity factors in patients with intracranial neoplasms and cerebrovascular pathology. Monitoring of intracranial pressure gives only an indirect and global measure of brain swelling. We have made an assessment of the applicability of Raman spectroscopy as an alternative method for assessing brain edema, which measures the water concentration in the tissue directly. Partial least-squares models were developed on the basis of Raman spectra measured in the 2600-3800-cm(-1) region, which predict the water fraction of brain tissue in the 0.75-0.95 range, with an accuracy better than 0.01.

Background After an aneurysmal subarachnoid hemorrhage, cerebral microcirculatory changes occur as a result cerebral vasospasm. The objective of this study is to investigate, with a computational model, how various degrees of vasospasm are influenced by increasing the mean blood pressure and decreasing the blood viscosity. Methods Using ANSYS CFX software, a computational model was constructed to simulate steady-state fully developed laminar blood flow through a rigid wall system consisting of the internal carotid artery (ICA), anterior cerebral artery, posterior cerebral artery, and middle cerebral artery (MCA). The MCA was selected for the site of a single acute vasospasm. Five severities of vasospasm were studied: 3 mm (normal), 2.5, 2, 1.5, and 1 mm. The ICA was assumed to have a constant inlet flow rate of 315 mL/min. The anterior cerebral artery and posterior cerebral artery were assumed to have constant outlet flow rates of 105 mL/min and 30 mL/min, respectively. The MCA was assumed to have a constant outlet pressure of 92 mL/min. Two different hematocrits, 45% and 32%, were simulated using the models. Results For a hematocrit of 45, the mean ICA inlet pressure required to pump blood through the system was 104 mm Hg for the 3-mm diameter MCA and 105, 108, 116, and 158 mm Hg for vasospasm diameters of 2.5, 2, 1.5, and 1 mm, respectively. For a hematocrit of 32, the mean ICA inlet pressure required was 102, 103, 105, 113, and 152 mm Hg, respectively. Conclusions The MCA required a large increase in mean ICA inlet pressure for vasospasm diameters less than 1.5 mm, which suggests that for vasospasms more than 50% diameter reduction, the blood pressure must be increased dramatically. Decreasing the hematocrit had minimal impact on blood flow in a constricted vessel.

Objective The diversion of cerebrospinal fluid (CSF) has been widely used in the prevention and treatment of CSF fistulae. A common method is the use of a lumbar drainage system. Although it is effective, several serious complications can develop, which can be avoided by regulating the flow of CSF with a standard intravenous infusion pump. Technique We present a simple, inexpensive, and accurate method of flow-controlled lumbar subarachnoid drainage that minimizes patient discomfort and the unpredictability of a gravity-dependent system. This system uses a standard lumbar drain connected to an intravenous infusion pump to provide drainage of CSF in a constant and predictable manner. Results A total of 42 patients from two institutions were treated with this method. CSF fistulae occurred secondary to trauma in 9 patients, after spinal surgery in 11 patients, after transsphenoidal surgery in 10 patients, and after cranial base surgery in 12 patients. Resolution of the fistula was attained in 36 of 42 patients. There were no deaths, no cases of deep venous thrombosis, and no incidence of meningitis. One patient developed tension pneumocephalus, and two patients developed headache with nausea and vomiting. All patients were ambulatory, and only three patients required narcotic analgesia for headaches. Conclusion Pump-regulated lumbar subarachnoid drainage is safe and effective in the treatment of CSF fistulae, as reported elsewhere in the literature. The advantage of this method is that the drainage of CSF can be carefully controlled and titrated in a predictable fashion. Because the system is independent of gravity to produce drainage of CSF, patients are not confined to bed and serious complications of overdrainage can be avoided.

Study Design. One hundred two patients with symptoms of cervical radiculopathy, were retrospectively analyzed and their cervical spinal cord diameters obtained. Objectives. To measure the cervical spinal cord in vivo and to compare the findings with those previously reported in the literature. Summary of Background Data. Traditionally, autopsy data have served as the linchpin of cervical cord measurements. However, several studies obtained by realtime radiographic methods have failed to confirm such measurements. Methods. The spinal cord was retrospectively measured in 102 patients. All patients underwent myelogram and postmyelogram computed tomographic scan. Anteroposterior and transverse diameters of the spinal cord were measured from C2 to T1 at the level of each intervertebral disc. The depth of the anterior median fissure and cross-sectional area were measured as well. Plain myelographic films were reviewed but demonstrated no findings contrary to postmyelogram computed tomographic measurements. Results. There was no statistically significant difference in the spinal cord measurements in relation to age or sex. There was an increase in the transverse diameter but not in the anteroposterior diameter in the midcervical spinal enlargement. The anteroposterior diameter decreased linearly. The transverse diameter and the cross-sectional area increased to a maximum at C5, as did the depth of the anterior median fissure. The cervical spinal cord diameter was documented to be 15-20% smaller than has commonly been determined by autopsy data. Conclusions. Postmyelogram computed tomographic measurements are smaller than those obtained from autopsy data.

We present a series of 21 patients, 12 males and 9 females, aged 41–76 years, with the preoperative diagnosis of a brain tumor. Both preoperatively and postoperatively, all of our patients underwent either a brain computed tomography (CT) or magnetic resonance imaging (MRI). All the radiographic studies were taped and loaded preoperatively in the Stereotactic Microscopic Navigator (SMN) workstation (Zeiss, Germany). The mean duration of this procedure was 25 ± 6 min. All our patients were operated on in our institute with the use of the SMN system. The specificity of tumor localization using CT scan was 2.20 ± 0.25 mm and for the MRI scan 2.6 ± 0.25 mm. As assessed by postoperative radiographic studies, total gross tumor resection was possible in 20 patients (95.23%). No major intraoperative or early postoperative complications were noted in our series. We believe that the SMN system is a safe, well-tolerated by the patients and simple method with extremely high accuracy and specificity.

In this paper, we used search engine technology to study outcome analysis and cost awareness of child hydrocephalus in the literature. The aggregate hospital charges of hydrocephalus treatment procedures for patients

Expenditure related to neurosurgery has increased unevenly since the early 1990s. In this study we explored the literature by which clinical evidence is obtained to better direct neurosurgical practice. We searched different types of neurosurgery literature and four major neurosurgical procedures (excision of brain lesion, cerebral aneurysm clipping/coiling, discectomy, spine fusion) written in English on PubMed from 1996, the year of its launch, using the keyword “cost”. Only a small and static portion of the neurosurgical literature was indexed as level I clinical evidence (randomized controlled trials), with a lack of cost appraisal in the outcome analysis of neurosurgical interventions. By way of rectification, a major increase in funding of grade I studies with cost analysis, and the requirement by peer-reviewed journals of a cost–benefit analysis, would promote the quality of clinical research yielding unquestionable advantage on national healthcare practice.

Postoperative fever is a common sequel of spine surgery. In the presence of rigid nationally mandated clinical guidelines, fever management may consume more health care resources than is reasonably appropriate.To study the relationship between postoperative fever, infection rate, and hospital charges in a cohort of spine surgery patients.We retrospectively reviewed 578 spine surgery patients (lumbar microdiskectomy [LMD], anterior cervical decompression and fusion [ACDF], and lumbar decompression and fusion [LDF]). Differences in length of stay and hospital charges as well as risk factors and correlation with infection and readmission rates were studied.Postoperative fever occurred in 41.7% of all spine surgery patients and more often in LDF patients (77.2%). Type of surgery was the most important variable affecting the prevalence of postoperative fever. Significant differences in length of stay were elicited between patients with and without postoperative fever in the ACDF and LMD groups and in hospital cost in the LMD group. The average length of stay was 2.41 vs 4.47 (P.01) in the LMD group, 1.67 vs 2.80 (P.05) in the ACDF group, and 5.03 vs 5.65 (P.05) in the LDF group. The average hospital charges were $16 261 vs $22 166 (P.01) in the LMD group, $26 021 vs $29 125 (P.05) in the ACDF group, and $53 627 vs $53 210 (P.05) in the LDF group. Obesity, female sex, and ≥102°F postoperative temperature were the most significant predictors of infection. Delayed discharge referable to postoperative fever did not seem to influence the infection readmission rate.Postoperative fever in spine surgery patients is associated with a delay in patient discharge and increases in hospital charges. Postoperative fever discharge guidelines should be regularly and publicly subjected to appropriate cost-benefit analysis.

Objective To study the role of drains in lumbar spine fusions. Methods The charts of 402 patients who underwent lumbar decompression and fusion (LDF) were retrospectively reviewed. Patients were classified per International Classification of Diseases, 9th Edition (ICD-9) procedure code as 81.07 (lateral fusion, 74.9%) and 81.08 (posterior fusion, 25.1%). The investigators studied the prevalence of drain use in lumbar fusion procedures and the impact of drain use on postoperative fever, wound infection, posthemorrhagic anemia, blood transfusion, and hospital cost. Results No significant differences in wound infection rates were noted between patients with and without drains (3.5% vs 2.6%, P = 0.627). The difference in postoperative fever rates between patients with and without drains (63.2% vs 52.6%, P = 0.05) was of borderline significance. Posthemorrhagic anemia was statistically more common in patients with drains (23.5% vs 7.7%, P = 0.000). Allogeneic blood transfusion was also statistically more common in the drained group (23.9% vs 6.8%, P = 0.000). Postoperative hemoglobin levels were lower in patients with drains who underwent one-level (9.5 g/dL vs 11.3 g/dL) or two-level (9.3 g/dL vs 10.2 g/dL) spine fusions. In this series in which drains were liberally used, no patient had to return to the operating room because of postoperative hematoma. An increased rate of allogeneic blood transfusion was noticed with posthemorrhagic anemia and drain use. The rate of allogeneic blood transfusion increased from 5.6% in patients without drains or posthemorrhagic anemia to 38.8% in patients with drains and posthemorrhagic anemia as a secondary diagnosis. The use of drains was associated with statistically insignificant increases in length of stay and cost in posterior procedures. Drain use was associated with shorter length of stay and hospital charges in lateral fusions of three or more levels. Conclusions Drain use did not increase the risk of wound infection in patients undergoing LDF, but it had some impact on the prevalence of postoperative fever. Drain use was significantly associated with posthemorrhagic anemia and allogeneic blood transfusion. Drain use did not have a significant economic impact on hospital length of stay and charges except in lateral procedures involving three or more levels.

Elevated levels of glycosylated hemoglobin (HbA1c) among spine surgery patients may have an impact on length of stay (LOS) and healthcare cost.We retrospectively reviewed the charts of 556 spine surgery patients who underwent 1 of 3 types of surgery: lumbar microdiscectomy (LMD), anterior cervical decompression and fusion (ACDF), and lumbar decompression and fusion (LDF). Information was collected about their diabetes mellitus (DM) history and HbA1c levels. We used HbA1c 6.1% as the screening cutpoint. Percentages of nondiabetic patients, those with subclinical elevation of HbA1c and those with already known DM were calculated and statistical analysis was applied.After excluding the small group of well-controlled DM (n = 14), 72.4% of patients were nondiabetic, 14.3% were subclinical patients with previously unknown HbA1c elevation, and 13.3% were already known, confirmed DM patients. There were significant differences in the LDF group between the "No DM" and "Subclinical" groups (P0.05) in terms of cost and LOS (P0.05). Age and body mass index (BMI) were very significant predictors of total cost in spine surgery patients (Por= 0.001), in addition to the type of surgery. Univariate analysis with age, BMI, or both as covariates deprived DM-HbA1c status of statistical significance (P0.05) in determining cost.There is a significant segment of spine surgery patients who were unaware of their elevated HbA1c status before their preoperative visit. These patients seem to utilize more healthcare resources, which is especially evident in the LDF group. We believe that HbA1c should be considered in the routine preoperative workup of spine surgery patients.

Object Cerebral vasospasm is a common and potentially devastating complication of aneurysmal subarachnoid hemorrhage (aSAH). Inflammatory processes seem to play a major role in the pathogenesis of vasospasm. The Creactive protein (CRP) constitutes a highly sensitive inflammatory marker. The association of elevated systemic CRP and coronary vasospasm has been well established. Additionally, elevation of the serum CRP levels has been demonstrated in patients with aSAH. The purpose of the current study was to evaluate the possible relationship between elevated CRP levels in the serum and CSF and the development of vasospasm in patients with aSAH. Methods . A total of 41 adult patients in whom aSAH was diagnosed were included in the study. Their demographics, the admitting Glasgow Coma Scale (GCS) score, Hunt and Hess grade, Fisher grade, CT scans, digital subtraction angiography studies, and daily neurological examinations were recorded. Serial serum and CSF CRP measurements were obtained on Days 0, 1, 2, 3, 5, 7, and 9. All patients underwent either surgical or endovascular treatment within 48 hours of their admission. The outcome was evaluated using the Glasgow Outcome Scale and the modified Rankin Scale. Results The CRP levels in serum and CSF peaked on the 3rd postadmission day, and the CRP levels in CSF were always higher than the serum levels. Patients with lower admission GCS scores and higher Hunt and Hess and Fisher grades had statistically significantly higher levels of CRP in serum and CSF. Patients with angiographic vasospasm had higher CRP measurements in serum and CSF, in a statistically significant fashion (p < 0.0001). Additionally, patients with higher CRP levels in serum and CSF had less favorable outcome in this cohort. Conclusions Patients with aSAH who had high Hunt and Hess and Fisher grades and low GCS scores showed elevated CRP levels in their CSF and serum. Furthermore, patients developing angiographically proven vasospasm demonstrated significantly elevated CRP levels in serum and CSF, and increased CRP measurements were strongly associated with poor clinical outcome in this cohort.

Generation of thrombin is associated with vascular remodeling that involves proliferation of vascular smooth muscle cells (SMCs) and activation of pro-matrix metalloproteinases (pro-MMPs). The present study was to investigate whether thrombin would induce mitogenesis and activation of pro-MMPs in cerebrovascular SMCs (CSMCs), and if so, whether MMP activity would contribute to the CSMC mitogenesis. CSMCs were cultured from pig middle cerebral arteries and stimulated with thrombin. Thrombin (0.1-5U/ml), in a dose-dependent fashion, stimulated mitogenesis in CSMCs as detected by bromo-2'-deoxy-uridine (BrdU) incorporation. Additionally, zymographic analyses showed that thrombin stimulated the appearance of the active form of MMP-2 (MMP-2) in a concentration-dependent manner, but not the release of pro-MMP-2. Thrombin did not affect expression of cell-associated pro-MMP-2 protein as evaluated by Western blot analysis. Treatment with the synthetic MMP inhibitor GM6001 or antibodies to MMP-2 significantly reduced thrombin-induced BrdU incorporation in CSMCs. In conclusion, thrombin activates pro-MMP-2 in the absence of elevated pro-MMP-2 expression and secretion in CSMCs, and thrombin induces CSMC mitogenesis involving its action on MMP-2. These findings suggest that thrombin may have relevance in cerebrovascular remodeling associated with brain atherosclerosis and atherothrombotic ischemic stroke through a mechanism involving MMP-dependent CSMC mitogenesis.

A 49-year-old white female presented to the emergency room complaining of severe headaches. A brain computed tomography (CT) showed a large right temporal mass that measured 2.9 x 5 cm. Sodium was low at admission, which indicated syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Her pituitary gland was enlarged. Thorax CT revealed a large anterior mediastinal mass measuring 6.3 x 3.6 cm. Pathology revealed a poorly differentiated carcinoma arising from the thymus. This case is unique because thymic cancer rarely results in brain metastases and very rarely causes SIADH with changes in pituitary volume and signal quality.