Characteristics and outcomes of patients undergoing lumbar spine surgery for axial back pain in the Michigan Spine Surgery Improvement Collaborative.

BACKGROUND CONTEXT: The indications for surgical intervention of axial back pain without leg pain for degenerative lumbar disorders have been limited in the literature, as most study designs allow some degree of leg symptoms in the inclusion criteria. PURPOSE: To determine the outcome of surgery (decompression only vs. fusion) for pure axial back pain without leg pain. STUDY DESIGN/SETTING: Prospectively collected data in the Michigan Spine Surgery Improvement Collaborative (MSSIC). PATIENT SAMPLE: Patients with pure axial back pain without leg pain underwent lumbar spine surgery for primary diagnoses of lumbar disc herniation, lumbar stenosis, and isthmic or degenerative spondylolisthesis ≤ grade II. OUTCOME MEASURES: Minimally clinically important difference (MCID) for back pain, Numeric Rating Scale of back pain, Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS-PF), MCID of PROMIS-PF, and patient satisfaction on the North American Spine Surgery Patient Satisfaction Index were collected at 90 days, 1 year, and 2 years after surgery. METHODS: Log-Poisson generalized estimating equation models were constructed with patient-reported outcomes as the independent variable, reporting adjusted risk ratios (RRadj). RESULTS: Of the 388 patients at 90 days, multi-level versus single level lumbar surgery decreased the likelihood of obtaining a MCID in back pain by 15% (RRadj=0.85, p=.038). For every one-unit increase in preoperative back pain, the likelihood for a favorable outcome increased by 8% (RRadj=1.08, p<.001). Of the 326 patients at 1 year, symptom duration > 1 year decreased the likelihood of a MCID in back pain by 16% (RRadj=0.84, p=.041). The probability of obtaining a MCID in back pain increased by 9% (RRadj=1.09, p<.001) for every 1-unit increase in baseline back pain score and by 14% for fusions versus decompression alone (RRadj=1.14, p=.0362). Of the 283 patients at 2 years, the likelihood of obtaining MCID in back pain decreased by 30% for patients with depression (RRadj=0.70, p<.001) and increased by 8% with every one-unit increase in baseline back pain score (RRadj=1.08, p<.001). CONCLUSIONS: Only the severity of preoperative back pain was associated with improvement in MCID in back pain at all time points, suggesting that surgery should be considered for selected patients with severe axial pain without leg pain. Fusion surgery versus decompression alone was associated with improved patient-reported outcomes at 1 year only, but not at the other time points.

Simvastatin and atorvastatin improve neurological outcome after experimental intracerebral hemorrhage.

BACKGROUND AND PURPOSE: This study investigates the effects of statin treatment on experimental intracerebral hemorrhage (ICH) using behavioral, histological, and MRI measures of recovery. METHODS: Primary ICH was induced in rats. Simvastatin (2 mg/kg), atorvastatin (2 mg/kg), or phosphate-buffered saline (n=6 per group) was given daily for 1 week. MRI studies were performed 2 to 3 days before ICH, and at 1 to 2 hours and 1, 2, 7, 14, and 28 days after ICH. The ICH evolution was assessed via hematoma volume measurements using susceptibility-weighted imaging (SWI) and tissue loss using T2 maps and hematoxylin and eosin (H&E) histology. Neurobehavioral tests were done before ICH and at various time points post-ICH. Additional histological measures were performed with doublecortin neuronal nuclei and bromodeoxyuridine stainings. RESULTS: Initial ICH volumes determined by SWI were similar across all groups. Simvastatin significantly reduced hematoma volume at 4 weeks (P=0.002 versus control with acute volumes as baseline), whereas that for atorvastatin was marginal (P=0.09). MRI estimates of tissue loss (% of contralateral hemisphere) for treated rats were significantly lower (P=0.0003 and 0.001, respectively) than for control at 4 weeks. Similar results were obtained for H&E histology (P=0.0003 and 0.02, respectively). Tissue loss estimates between MRI and histology were well correlated (R2=0.764, P<0.0001). Significant improvement in neurological function was seen 2 to 4 weeks post-ICH with increased neurogenesis observed. CONCLUSIONS: Simvastatin and atorvastatin significantly improved neurological recovery, decreased tissue loss, and increased neurogenesis when administered for 1 week after ICH.

A novel calpastatin-based inhibitor improves postischemic neurological recovery.

Calpastatin, a naturally occurring protein, is the only inhibitor that is specific for calpain. A novel blood-brain barrier (BBB)-permeant calpastatin-based calpain inhibitor, named B27-HYD, was developed and used to assess calpain's contribution to neurological dysfunction after stroke in rats. Postischemic administration of B27-HYD reduced infarct volume and neurological deficits by 35% and 44%, respectively, compared to untreated animals. We also show that the pharmacologic intervention has engaged the intended biologic target. Our data further demonstrates the potential utility of SBDP145, a signature biomarker of acute brain injury, in evaluating possible mechanisms of calpain in the pathogenesis of stroke and as an adjunct in guiding therapeutic decision making.

Patient Demographic and Surgical Factors that Affect Completion of Patient-Reported Outcomes 90 Days and 1 Year After Spine Surgery: Analysis from the Michigan Spine Surgery Improvement Collaborative (MSSIC).

BACKGROUND: The Michigan Spine Surgery Improvement Collaborative is a statewide multicenter quality improvement registry. Because missing data can affect registry results, we used MSSIC to find demographic and surgical characteristics that affect the completion of patient-reported outcomes (PROs) at 90 days and 1 year. METHODS: A total of 24,404 patients who had lumbar surgery (17,813 patients) or cervical surgery (6591 patients) were included. Multivariate logistic regression models of patient disease were constructed to identify risk factors for failure to complete scheduled PRO surveys. RESULTS: Patients ≥65 years old and female patients were both more likely to respond at 90 days and 1 year. Increasing education was associated with greater response rate at 90 days and 1 year. Whites and African Americans had no differences in response rates. Calling provided the highest response rate at 90 days and 1 year. For cervical spine patients, only discharge to rehabilitation increased completion rates, at 90 days but not 1 year. For lumbar spine patients, spondylolisthesis or stenosis (vs. herniated disc) had a greater response rate at 1 year. Patients with leg (vs. back) pain had a greater response only at 1 year. Patients with multilevel surgery had an increased response at 1 year. Patients who underwent fusion were more likely to respond at 90 days, but not 1 year. Discharge to rehabilitation increased response at 90 days and 1 year. CONCLUSIONS: A multivariate analysis from a multicenter prospective database identified surgical factors that affect PRO follow-up, up to 1 year. This information can be helpful for imputing missing PRO data and could be used to strengthen data derived from large prospective databases.

Temporal MRI assessment of intracerebral hemorrhage in rats.

BACKGROUND AND PURPOSE: MRI was used to evaluate the effects of experimental intracerebral hemorrhage (ICH) on brain tissue injury and recovery. METHODS: Primary ICH was induced in rats (n=6) by direct infusion of autologous blood into the striatum. The evolution of ICH damage was assessed by MRI estimates of T(2) and T(1sat) relaxation times, cerebral blood flow, vascular permeability, and susceptibility-weighted imaging before surgery (baseline) and at 2 hours and 1, 7, and 14 days post-ICH. Behavioral testing was done before and at 1, 7, and 14 days post-ICH. Animals were euthanized for histology at 14 days. RESULTS: The MRI appearance of the hemorrhage and surrounding regions changed in a consistent manner over time. Two primary regions of interest were identified based on T(2) values. These included a core, corresponding to the bulk of the hemorrhage, and an adjacent rim; both varied with time. The core was associated with significantly lower cerebral blood flow values at all post-ICH time points, whereas cerebral blood flow varied in the rim. Increases in vascular permeability were noted at 1, 7, and 14 days. Changes in T(1sat) were similar to those of T(2). MRI and histological estimates of tissue loss were well correlated and showed approximately 9% hemispheric tissue loss. CONCLUSIONS: Although the cerebral blood flow changes observed with this ICH model may not exactly mimic the clinical situation, our results suggest that the evolution of ICH injury can be accurately characterized with MRI. These methods may be useful to evaluate therapeutic interventions after experimental ICH and eventually in humans.

Effects of cathepsins B and L inhibition on postischemic protein alterations in the brain.

The effects of selective inhibition of cathepsins B and L on postischemic protein alterations in the brain were investigated in a rat model of middle cerebral artery occlusion (MCAO). Cathepsin B activity increased predominantly in the subcortical region of the ischemic hemisphere where the levels of collapsing mediator response protein 2, heat shock cognate 70 kDa protein, 60 kDa heat shock protein, protein disulfide isomerase A3 and albumin, were found to be significantly elevated. Postischemic treatment with Cbz-Phe-Ser(OBzl)-CHN(2), cysteine protease inhibitor 1 (CP-1), reduced infarct volume, neurological deficits and cathepsin B activity as well as the amount of heat shock proteins and albumin found in the brain. Our data strongly suggests that the decrease in heat shock protein levels and the significant reduction of serum albumin leakage into the brain following acute treatment with CP-1 is indicative of less secondary ischemic damage, which ultimately, is related to less cerebral tissue loss and improved neurological recovery of the animals.

Mannitol enhances delivery of marrow stromal cells to the brain after experimental intracerebral hemorrhage.

Previous studies show that intravascular injection of human bone marrow stromal cells (hBMSCs) significantly improves neurological functional recovery in a rat model of intracerebral hemorrhage (ICH). In the present study, we tested the hypothesis that mannitol improves the efficiency of intraarterial MSC delivery (i.e., fewer injected cells required for therapeutic efficacy) after ICH. There were four post-ICH groups (N=9): group 1, negative control with only intraarterial injection of 1 million human fibroblasts in phosphate-buffered saline (PBS); group 2, intravenous injection of mannitol alone in PBS (1.5 g/kg); group 3, intraarterial injection of 1 million hBMSCs alone in PBS; and group 4, intravenous injection of mannitol (1.5 g/kg) in PBS followed by intraarterial injection of 1 million hBMSCs in PBS. Group 4 exhibited significantly improved neurological functional outcome as assessed by neurological severity score (NSS) and corner test scores. Immunohistochemical staining of group 4 suggested increased synaptogenesis, proliferating immature neurons, and neuronal migration. The number of hBMSCs recruited to the injured region increased strikingly in group 4. Tissue loss was notably reduced in group 4. In summary, the beneficial effects of intraarterial infusion of MSCs are amplified with intravenous injection of mannitol. Preadministration of mannitol significantly increases the number of hBMSCs located in the ICH region, improves histochemical parameters of neural regeneration, and reduces the anatomical and pathological consequences of ICH.

Multipotent mesenchymal stromal cell-derived exosomes improve functional recovery after experimental intracerebral hemorrhage in the rat.

OBJECTIVE: Previous studies have demonstrated that transplanted multipotent mesenchymal stromal cells (MSCs) improve functional recovery in rats after experimental intracerebral hemorrhage (ICH). In this study the authors tested the hypothesis that administration of multipotent MSC-derived exosomes promotes functional recovery, neurovascular remodeling, and neurogenesis in a rat model of ICH. METHODS: Sixteen adult male Wistar rats were subjected to ICH via blood injection into the striatum, followed 24 hours later by tail vein injection of 100 µg protein of MSC-derived exosomes (treatment group, 8 rats) or an equal volume of vehicle (control group, 8 rats); an additional 8 rats that had identical surgery without blood infusion were used as a sham group. The modified Morris water maze (mMWM), modified Neurological Severity Score (mNSS), and social odor-based novelty recognition tests were performed to evaluate cognitive and sensorimotor functional recovery after ICH. All 24 animals were killed 28 days after ICH or sham procedure. Histopathological and immunohistochemical analyses were performed for measurements of lesion volume and neurovascular and white matter remodeling. RESULTS: Compared with the saline-treated controls, exosome-treated ICH rats showed significant improvement in the neurological function of spatial learning and motor recovery measured at 26-28 days by mMWM and starting at day 14 by mNSS (p < 0.05). Senorimotor functional improvement was measured by a social odor-based novelty recognition test (p < 0.05). Exosome treatment significantly increased newly generated endothelial cells in the hemorrhagic boundary zone, neuroblasts and mature neurons in the subventricular zone, and myelin in the striatum without altering the lesion volume. CONCLUSIONS: MSC-derived exosomes effectively improve functional recovery after ICH, possibly by promoting endogenous angiogenesis and neurogenesis in rats after ICH. Thus, cell-free, MSC-derived exosomes may be a novel therapy for ICH.

Preventive effect of tamsulosin on postoperative urinary retention in neurosurgical patients.

BACKGROUND: Postoperative urinary retention (POUR) is common in neurosurgical patients. The use of alpha-blockade therapy, such as tamsulosin, has benefited many patients with a history of obstructive uropathy by decreasing lower urinary tract symptoms such as distension, infections, and stricture formation, as well as the incidence of POUR. For this study, we targeted patients who had undergone spinal surgery to examine the prophylactic effects of tamsulosin. Increased understanding of this therapy will assist in minimizing the morbidity of spinal surgery. METHODS: We enrolled 95 male patients undergoing spine surgery in a double-blind, randomized, placebo-controlled trial. Patients were randomly assigned to receive either preoperative tamsulosin (N = 49) or a placebo (N = 46) and then followed-up prospectively for the development of POUR after removal of an indwelling urinary catheter (IUC). They were also followed-up for the incidence of IUC reinsertions. RESULTS: The rate of developing POUR was similar in both the groups. Of the 49 patients given tamsulosin, 16 (36%) developed POUR compared to 13 (28%) from the control group (P = 0.455). In the control group, 5 (11%) patients had IUC re-inserted postoperatively, whereas 7 (14%) patients in the tamsulosin group had IUC re-inserted postoperatively (P = 0.616). In patients suffering from axial-type symptoms (i.e., mechanical back pain), 63% who received tamsulosin and 18% from the control group (P = 0.048) developed POUR. CONCLUSION: Overall, there was no statistically significant difference in the rates of developing POUR among patients in either group. POUR is caused by a variety of factors, and further studies are needed to shed light on its etiology.

Effects of intravenous administration of human bone marrow stromal cells after intracerebral hemorrhage in rats.

OBJECT: The goal of this study was to investigate whether human bone marrow stromal cells (hBMSCs) administered by intravenous injection have a beneficial effect on outcome after intracerebral hemorrhage (ICH) in rats. METHODS: An ICH was induced in 54 adult male Wistar rats by a stereotactically guided injection of autologous blood into the right striatum. Intravenous infusion of the hBMSCs (3, 5, or 8 million cells) was performed 1 day after ICH, and for each dose group there was a control group that received injections of vehicle. Neurological function, which was evaluated using the Neurological Severity Score (NSS) and the corner turn test, was tested before and at 1, 7, and 14 days after ICH. After 14 days of survival, the area of encephalomalacia was calculated and histochemical labeling was performed. For all three groups, there were no statistical differences in either the NSS or corner turn tests after 1 day. After 7 and 14 days, however, the three groups that received the hBMSCs showed significant improvement in functional scores compared with the control group. In addition, after 14 days there was significantly more striatal tissue loss in the placebo groups compared with each of the three treatment groups. The region of injury in the treated animals demonstrated a significantly increased presence of hBMSCs, immature neurons, neuronal migration, synaptogenesis, and newly formed DNA. CONCLUSIONS: Intravenous administration of hBMSCs significantly improves neurological function in rats subjected to ICH. This improvement in the treated animals is associated with reduced tissue loss and increased local presence of the hBMSCs, mitotic activity, immature neurons, synaptogenesis, and neuronal migration.

Development of De Novo Arteriovenous Malformation Following Ischemic Stroke: Case Report and Review of Current Literature.

BACKGROUND: Arteriovenous malformations (AVMs) are hypothesized to be static, congenital lesions developing as early as 4 weeks of fetal life. New literature has shown that AVMs may represent dynamic and reactive vascular lesions arising from cerebral infarction, inflammation, or trauma. A literature search reveals 17 previously reported cases of new AVM formation after previous negative imaging studies. This reactive development or "second hit" theory suggests that at a molecular level, growth factors may play a vital role in aberrant angiogenesis and maturation of an arteriovenous fistula into an AVM. CASE DESCRIPTION: A 52-year-old female presented with a ruptured left frontal AVM demonstrated by computed tomography angiography and digital subtraction angiography. The patient had suffered an acute ischemic stroke in the similar cerebral vascular territory 8 years prior due to left internal carotid artery occlusion. Detailed neuroimaging at that time failed to reveal any vascular malformation, suggesting that the AVM might have developed in response to initial vascular insult. CONCLUSIONS: We believe that there might exist a subset of AVMs that display dynamic characteristics and could potentially appear, grow, or resolve spontaneously without intervention, especially in the presence of local growth factors and molecular signaling cascades. When combined with a previous cerebral insult such as stroke, trauma, or inflammation, de novo AVM formation may represent a "second hit" with abnormal angiogenesis and vessel formation.

Management of arteriovenous malformations in the elderly: a single-center case series and analysis of outcomes.

OBJECT Treatment of brain arteriovenous malformations (bAVMs) in the elderly remains a challenge for cerebrovascular surgeons. In this study the authors reviewed the patient characteristics, treatments, angiographic results, and clinical outcomes in 28 patients over 65 years of age who were treated at Henry Ford Hospital between 1990 and 2014. METHODS The bAVM database at the authors' institution was queried for records of elderly patients with bAVMs, and data regarding patient demographics, presenting symptoms, bAVM angioarchitecture, treatment modalities, angiographic results, clinical outcomes, and treatment complications were tabulated and analyzed. RESULTS There were 9 male (32%) and 19 female (68%) patients, with an average age ( ± SD) of 73.0 ± 6.95 years. The most common symptoms on presentation were hemorrhage (36%) and headaches (18%). The bAVMs were equally distributed between the supra- and infratentorial compartments. The most common Spetzler-Martin grade was II, observed in 57% of the patients. Eleven patients (39.3%) underwent resection, 4 patients (14.3%) received standalone radiation therapy, and 13 patients (46%) did not receive treatment or were managed expectantly. Four patients (14.3%) were lost to follow-up. Complete bAVM obliteration was achieved in 87% of the treated patients. None of the patients who received any form of treatment died; the overall mortality rate was 3.6%. CONCLUSIONS Surgical management of bAVMs in the elderly can result in complete obliteration and acceptable clinical outcomes.

Stent-within-a-stent technique for the treatment of dissecting vertebral artery aneurysms.

Subarachnoid hemorrhage from dissecting vertebral artery aneurysms is a well-known phenomenon. With the advent of navigable intracranial stents, these aneurysms are now amenable to endovascular stent placement. However, immediate aneurysm obliteration is often not accomplished, and current covered stents have poor short-term patency rates. We report a series of three patients with intradural dissecting vertebral artery aneurysms treated with a novel endovascular stent-within-a-stent construct using currently available stent technology.

Improvement in neurological outcome after administration of atorvastatin following experimental intracerebral hemorrhage in rats.

OBJECT: Atorvastatin, a beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitor, improves neurological functional outcome, reduces cerebral cell loss, and promotes regional cellular plasticity when administered after intracerebral hemorrhage (ICH) in rats. METHODS: Autologous blood was stereotactically injected into the right striatum in rats, and atorvastatin was administered orally beginning 24 hours after ICH and continued daily for 1 week. At a dose of 2 mg/kg, atorvastatin significantly reduced the severity of neurological deficit from 2 to 4 weeks after ICH. The area of cell loss in the ipsilateral striatum was also significantly reduced in these animals. Consistent with previous study data, higher doses of atorvastatin (8 mg/kg) did not improve functional outcome or reduce the extent of injury. Histochemical stains for markers of synaptogenesis, immature neurons, and neuronal migration revealed increased labeling in the region of hemorrhage in the atorvastatin-treated rats. CONCLUSIONS: Analysis of the data in this study indicates that atorvastatin improves neurological recovery after experimental ICH and may do so in part by increasing neuronal plasticity.

Magnesium sulfate therapy after aneurysmal subarachnoid hemorrhage.

OBJECT: Vasospasm remains a significant source of neurological morbidity and mortality following aneurysmal subarachnoid hemorrhage (SAH), despite advances in current medical, surgical, and endovascular therapies. Magnesium sulfate therapy has been demonstrated to be both safe and effective in preventing neurological complications in obstetrical patients with eclampsia. Evidence obtained using experimental models of brain injury, cerebral ischemia, and SAH indicate that Mg may also have a role as a neuroprotective agent. The authors hypothesize that MgSO4 therapy is safe, feasible, and has a beneficial effect on vasospasm and, ultimately, on neurological outcome following aneurysmal SAH. METHODS: A prospective randomized single-blind clinical trial of high-dose MgSO4 therapy following aneurysmal SAH (Hunt and Hess Grades II-IV) was performed in 40 patients, who were enrolled within 72 hours following SAH and given intravenous MgSO4 or control solution for 10 days. Serum Mg++ levels were maintained in the 4 to 5.5 mg/dl range throughout the treatment period. Clinical management principles were the same between groups (including early use of surgery or endovascular treatment, followed by aggressive vasospasm prophylaxis and treatment). Daily transcranial Doppler (TCD) ultrasonographic recordings were obtained, and clinical outcomes were measured using the Glasgow Outcome Scale (GOS). The patients' GOS scores and the TCD recordings were analyzed using the independent t-test. Forty patients were enrolled in the study: 20 (15 female and five male patients) received treatment and 20 (11 female and nine male patients) comprised a control group. The mean ages of the patients in these groups were 46 and 51, respectively, and the mean clinical Hunt and Hess grades were 2.6 +/- 0.68 in the MgSO4 treatment group and 2.3 +/- 0.73 in the control group (mean +/- standard deviation [SD], p = 0.87). Fisher grades were similar in both groups. Mean middle cerebral artery velocities were 93 +/- 27 cm/second in MgSO4-treated patients and 102 +/- 34 cm/second in the control group (mean +/- SD, p = 0.41). Symptomatic vasospasm, confirmed by angiography, occurred in six of 20 patients receiving MgSO4 and in five of 16 patients receiving placebo. Mean GOS scores were 3.8 +/- 1.6 and 3.6 +/- 1.5 (mean +/- SD, p = 0.74) in the treatment and control groups, respectively. Significant adverse effects from treatment with MgSO4 did not occur. CONCLUSIONS: Administration of high-dose MgSO4 following aneurysmal SAH is safe, and steady Mg++ levels in the range of 4 to 5.5 mg/dl are easily maintained. This treatment does not interfere with neurological assessment, administration of anesthesia during surgery, or other aspects of clinical care. We observed a trend in which a higher percentage of patients obtained GOS scores of 4 or 5 in the group treated with MgSO4, but the trend did not reach a statistically significant level. A larger study is needed to evaluate this trend further.

Carotid endarterectomy in patients with contralateral internal carotid artery occlusion without intraoperative shunting.

BACKGROUND: Controversy about the optimal method of performing a carotid endarterectomy (CEA) exists despite its widespread application and support from various randomized clinical trials. Many surgeons selectively or routinely use electroencephalography (EEG) monitoring as well as shunting when performing this operation. METHODS: We conducted this retrospective study to assess the maximum carotid clamp time without shunting or EEG monitoring during a CEA without the development of neurological deficits in an already compromised cerebral circulation. RESULTS: Fifteen consecutive patients who underwent CEAs between 1988 and 1999 met our criteria of angiographically documented ipsilateral internal carotid artery (ICA) stenosis with contralateral ICA occlusion. The patient presentations included asymptomatic (14%), transient ischemic attack (TIA) (50%), and stroke (36%). All patients were operated under general anesthesia without shunting and only 4 patients underwent EEG monitoring. On angiography, all 15 patients had ipsilateral ICA stenosis (70-99%) and contralateral occlusion. In 54% of patients, the vertebral arteries (VAs) were both patent, while in 46% of patients only 1 VA was patent. Eighty-five percent of patients had at least 1 patent anterior communicating (Pcomm) artery, while 15% had nonvisualized Pcomm arteries bilaterally. Of the 15 patients, 14 had a patent anterior communicating artery. The mean clamp time of the CCA was 18.5 minutes (range 14-30 minutes). None of the 15 patients had new neurological changes immediately postoperatively or during the 6 weeks of follow-up. CONCLUSION: We propose that shunting may not be necessary during CEA for high-grade stenosis with contralateral ICA occlusion, presumably because of adequate distal small vessel collaterals.

Acute Statin Treatment Improves Recovery after Experimental Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: We have previously demonstrated that 2-week treatment of experimental intracerebral hemorrhage (ICH) with a daily dose of 2 mg/kg statin starting 24 hours post-injury exerts a neuroprotective effect. The present study extends our previous investigation and tests the effect of acute high-dose (within 24 hours) statin therapy on experimental ICH. MATERIAL AND METHODS: Fifty-six male Wistar rats were subjected to ICH by stereotactic injection of 100 µl of autologous blood into the striatum. Rats were divided randomly into seven groups: saline control group (n = 8); 10, 20 and 40 mg/kg simvastatin-treated groups (n = 8); and 10, 20 and 40 mg/kg atorvastatin-treated groups (n = 8). Simvastatin or atorvastatin were administered orally at 3 and 24 hours after ICH. Neurological functional outcome was evaluated using behavioral tests (mNSS and corner turn test) at multiple time points after ICH. Animals were sacrificed at 28 days after treatment, and histological studies were completed. RESULTS: Acute treatment with simvastatin or atorvastatin at doses of 10 and 20 mg/kg, but not at 40 mg/kg, significantly enhanced recovery of neurological function starting from 2 weeks post-ICH and persisting for up to 4 weeks post ICH. In addition, at doses of 10 mg/kg and 20 mg/kg, histological evaluations revealed that simvastatin or atorvastatin reduced tissue loss, increased cell proliferation in the subventricular zone and enhanced vascular density and synaptogenesis in the hematoma boundary zone when compared to saline-treated rats. CONCLUSIONS: Treatment with simvastatin or atorvastatin at doses of 10 and 20 mg/kg significantly improves neurological recovery after administration during the first 24 hours after ICH. Decreased tissue loss, increased cell proliferation and vascularity likely contribute to improved functional recovery in rats treated with statins after ICH.

Statins Protect the Blood Brain Barrier Acutely after Experimental Intracerebral Hemorrhage.

OBJECTIVES: The goal of this study was to measure the impact of simvastatin and atorvastatin treatment on blood brain barrier (BBB) integrity after experimental intracerebral hemorrhage (ICH). METHODS: Primary ICH was induced in 27 male Wistar rats by stereotactic injection of 100 µL of autologous blood into the striatum. Rats were divided into three groups (n= 9/group): 1) oral treatment (2 mg/kg) of atorvastatin, 2) oral treatment (2 mg/kg) simvastatin, or 3) phosphate buffered saline daily starting 24-hours post-ICH and continuing daily for the next 3 days. On the fourth day, the animals underwent magnetic resonance imaging (MRI) for measurements of T1sat (a marker for BBB integrity), T2 (edema), and cerebral blood flow (CBF). After MRI, the animals were sacrificed and immunohistology or Western blotting was performed. RESULTS: MRI data for animals receiving simvastatin treatment showed significantly reduced BBB dysfunction and improved CBF in the ICH rim compared to controls (P<0.05) 4 days after ICH. Simvastatin also significantly reduced edema (T2) in the rim at 4 days after ICH (P<0.05). Both statin-treated groups demonstrated increased occludin and endothelial barrier antigen levels within the vessel walls, indicating better preservation of BBB function (P<0.05) and increased number of blood vessels (P<0.05). CONCLUSIONS: Simvastatin treatment administered acutely after ICH protects BBB integrity as measured by MRI and correlative immunohistochemistry. There was also evidence of improved CBF and reduced edema by MRI. Conversely, atorvastatin showed a non-significant trend by MRI measurement.

The incidence and risk factors for postoperative urinary retention in neurosurgical patients.

BACKGROUND: Postoperative urinary retention (POUR) is a common problem in adult neurosurgical patients. The incidence of POUR is unknown and the etiology has not been well established. POUR can lead to urogenital damage, prolonged hospital stay, higher cost, and infection. This study elucidates several risk factors that contribute to POUR in a variety of neurosurgical patients in one institution. METHODS: A total of 137 neurosurgical patients were prospectively followed up for the development of POUR, which we defined as initial postvoid residual (PVR1) >250 ml 6 hours after removal of an indwelling urinary catheter (IUC). For patients with PVR >250 ml on the third check, IUCs were reinserted and kept in for 5-7 days. RESULTS: Of the 137 patients, 68 (50%) were male, 41% (56/137) were 60 years or older, 86% (118/137) underwent spinal surgery, and 54% (74/137) had anesthesia over 200 minutes. Overall incidence of clinical POUR was 39.4% (54/137). Significantly higher rates of PVR1 >250 were noted in males, patients older than 60 years, and those who underwent spine surgery. When considering all patient characteristics (except selective alpha blockers), only gender, surgery time, and surgery type remained significant. In addition, PVR1 >250 was positively associated with longer length of stay. Of all patients, 24 (18%) had IUCs reinserted postoperatively or should have had one (5 refused and 2 had a third PVR). The association of IUC reinsertion with male gender was significant. CONCLUSION: Male gender, time of anesthesia >200 minutes, older age, and spinal surgery are the most significant risk factors associated with POUR in neurosurgical patients.

Therapeutic effect of human umbilical tissue-derived cell treatment in rats with experimental intracerebral hemorrhage.

BACKGROUND AND PURPOSE: The present study examines whether human umbilical tissue-derived cells (hUTC) have a neuro-restorative effect and improve functional recovery after intracerebral hemorrhage (ICH) in rats. METHODS: Primary ICH was induced in male Wistar rats by stereotactic injection of 100µL of autologous blood into the striatal region adjacent to the subventricular zone. Briefly, the rats were randomly divided into six groups, each group was intravenously injected either with 2mL phosphate-buffered saline (PBS) or 3million hUTC in PBS at 1, 3 or 7days after ICH (n=8/group). To evaluate neurological functional outcome, each animal was subjected to the modified neurological severity score (mNSS) and corner turn tests at different time points after ICH. At four weeks post treatment, each group was anesthetized intraperitoneally, sacrificed, and brain tissues were processed histologically. Immunohistochemistry was employed to measure vascularity (vWF), neurogenesis (BrdU TUJ1, DCX and NeuN), synaptogenesis (synaptophysin) and apoptosis (TUNEL). RESULTS: The hUTC-treated animals showed significantly improved neurological functional outcomes as assessed by mNSS and corner turn tests at 14, 21 and 28days post-injection in each treatment group (P<0.05) as compared to the PBS controls. Animals treated with hUTC were seen to have significantly increased cell proliferation, vascularity and synaptogenesis, as well as reduced apoptosis in the hematoma rim compared to the corresponding control group (P<0.05). CONCLUSIONS: Intravenously infused hUTC have a beneficial effect after experimental ICH by functional and histochemical measurements of neural cell proliferation and synaptogenesis in the ICH border zone. This brain region also shows correlative evidence of neuronal recovery with increased vascularity.