Red Blood Cell Distribution Width is Associated with Poor Clinical Outcome After Subarachnoid Hemorrhage: A Pilot Study.

INTRODUCTION: The red cell distribution width (RDW) is a biomarker strongly associated with poor outcome in inflammatory and thrombotic diseases. Subarachnoid hemorrhage (SAH) is both an inflammatory and thrombotic state in which many biomarkers have been studied. In this exploratory pilot study, we sought to determine whether RDW predicts poor outcome in patients with SAH. METHODS: Patients with moderate-to-severe SAH were prospectively enrolled in an observational study of biomarkers and outcome. CBC, ESR, high sensitivity CRP, D-dimer, and fibrinogen were obtained on post-bleed days (PBD) 1, 3, 5, 7, and 10. Poor outcome was defined as a modified Rankin score of 3-6 at 90-days. RESULTS: Of 40 patients, 5 (12.5%) died and 19 (47.5%) had a poor outcome. RDW (p = 0.046) when measured serially over the study period, was significantly higher among patients with poor outcome. Maximum RDW (OR 2.3 95% CI 1.2-3.6; p = 0.014) and maximum WBC count (OR 1.29 95% CI 1.04-1.60; p = 0.018) were associated with poor outcome. Stepwise addition of maximum ESR, CRP, D-dimer, and fibrinogen yielded a model with RDW (OR 2.54 95% CI 1.21-5.35; p = 0.014) and fibrinogen (OR 1.01 95% CI 1.002-1.01; p = 0.004) predicting outcome. With addition of age and Hunt and Hess grade, RDW, fibrinogen, and high-grade status remained significantly associated with poor outcome. Use of PBD1 RDW in lieu of maximum RDW, resulted in a similar model. CONCLUSIONS: An elevated RDW is associated with poor outcome in SAH patients. RDW may be a useful predictor of outcomes after SAH.

Early predictors of unfavourable outcome in subjects with moderate head injury in the emergency department.

BACKGROUND: Subjects with moderate head injury are a particular challenge for the emergency physician. They represent a heterogeneous population of subjects with large variability in injury severity, clinical course and outcome. We aimed to determine the early predictors of outcome of subjects with moderate head injury admitted to an Emergency Department (ED) of a general hospital linked via telemedicine to the Regional Neurosurgical Centre. PATIENTS AND METHODS: We reviewed, prospectively, 12,675 subjects attending the ED of a General Hospital between 1999 and 2005 for head injury. A total of 309 cases (2.4%) with an admission Glasgow Coma Scale (GCS) 9-13 were identified as having moderate head injury. The main outcome measure was an unfavourable outcome at 6 months after injury. The predictive value of a model based on main entry variables was evaluated by logistic regression analysis. FINDINGS: 64.7% of subjects had a computed tomographic scan that was positive for intracranial injury, 16.5% needed a neurosurgical intervention, 14.6% had an unfavourable outcome at 6 months (death, permanent vegetative state, permanent severe disability). Six variables (basal skull fracture, subarachnoid haemorrhage, coagulopathy, subdural haematoma, modified Marshall category and GCS) predicted an unfavourable outcome at 6 months. This combination of variables predicts the 6-month outcome with high sensitivity (95.6%) and specificity (86.0%). INTERPRETATION: A group of selected variables proves highly accurate in the prediction of unfavourable outcome at 6 months, when applied to subjects admitted to an ED of a General Hospital with moderate head injury.

Observational approach to subjects with mild-to-moderate head injury and initial non-neurosurgical lesions.

BACKGROUND: The model of care for patients with mild-to-moderate head injury and CT-detected lesions that do not require an immediate intervention is a matter of debate. This study compared the effects on outcome of a model based either on observation in a neurosurgical unit (NSU) or in a peripheral hospital (PH), making use of neurosurgical expertise via a teleradiology system. PATIENTS AND METHODS: The investigation reviewed the data that was prospectively collected in 865 cases with mild-to-moderate head injury and positive CT scan, not needing immediate neurosurgical evacuation. Outcome was determined at 6 months. The predictive value of location of observation on outcome was evaluated by logistic regression, after adjustment for the propensity score to the type of observation (calculated on main entry variables). FINDINGS: 700 subjects had a mild head injury, 105 had a moderate injury with GCS 13-11 and 60 with Glasgow Coma Scale (GCS) 10-9. Only 152/865 subjects (17.6%) were admitted to a NSU. During observation, neurosurgery was necessary in 117 cases (13.5%), 74/152 (48.7%) NSU-observed patients and 43/713 (6.0%; p<0.001) PH-observed cases. The outcome was unfavourable in 18% of the NSU cases versus 10% of the PH cases (p = 0.143). After correction for propensity, no significant differences were found between models of observation (NSU vs. PH; odds ratio, 0.92; 95% confidence interval, 0.49 to 1.75). INTERPRETATION: A model of care based on observation in PH with neurosurgical consult by teleradiology system, repeat CT scanning and transfer time 30-60 min to a NSU is not detrimental for subjects with initial non-neurosurgical lesions after mild-to-moderate head injury.

Characterization of the role of AMP-activated protein kinase in the regulation of glucose-activated gene expression using constitutively active and dominant negative forms of the kinase.

In the liver, glucose induces the expression of a number of genes involved in glucose and lipid metabolism, e.g., those encoding L-type pyruvate kinase and fatty acid synthase. Recent evidence has indicated a role for the AMP-activated protein kinase (AMPK) in the inhibition of glucose-activated gene expression in hepatocytes. It remains unclear, however, whether AMPK is involved in the glucose induction of these genes. In order to study further the role of AMPK in regulating gene expression, we have generated two mutant forms of AMPK. One of these (alpha1(312)) acts as a constitutively active kinase, while the other (alpha1DN) acts as a dominant negative inhibitor of endogenous AMPK. We have used adenovirus-mediated gene transfer to express these mutants in primary rat hepatocytes in culture in order to determine their effect on AMPK activity and the transcription of glucose-activated genes. Expression of alpha1(312) increased AMPK activity in hepatocytes and blocked completely the induction of a number of glucose-activated genes in response to 25 mM glucose. This effect is similar to that observed following activation of AMPK by 5-amino-imidazolecarboxamide riboside. Expression of alpha1DN markedly inhibited both basal and stimulated activity of endogenous AMPK but had no effect on the transcription of glucose-activated genes. Our results suggest that AMPK is involved in the inhibition of glucose-activated gene expression but not in the induction pathway. This study demonstrates that the two mutants we have described will provide valuable tools for studying the wider physiological role of AMPK.

Deep brain stimulation for Alzheimer disease: a decision and cost-effectiveness analysis.

Alzheimer disease (AD) is characterized by impairments in memory function. Standard AD treatment provides marginal improvements in this domain. Recent reports, however, suggested that deep brain stimulation (DBS) may result in improved memory. Given significant equipment costs and health expenses required for DBS surgery, we determine clinical and economic thresholds required for it to be as effective as standard AD treatment. Literature review yielded annual AD progression probabilities, health-related quality of life (QoL), and costs by AD stage. Our 5-year decision analysis model compared cumulative QoL in quality-adjusted life years (QALYs) and costs of standard therapy to theoretical DBS treatment of various success rates, using known complication rates and QoL data. The base case was a patient with mild-stage AD. DBS success was defined as regression to and maintenance of minimal stage AD, which was defined as midway between mild and no dementia, for the first year, and continuation of the natural course of AD for the remaining 4 years. Compared to standard treatment alone, DBS for mild-stage AD requires a success rate of 3% to overcome effects of possible surgical complications on QoL. If DBS can be delivered with success rates above 20% ($200 K/QALY) or 74% ($50 K/QALY) for mild AD, it can be considered cost-effective. Above a success rate of 80%, DBS treatment is both clinically more effective and more cost-effective than standard treatment. Our findings demonstrate that clinical and economic thresholds required for DBS to be cost-effective for AD are relatively low.

Is myelomeningocele a disappearing disease?

The incidence of major congenital anomalies of the central nervous system was determined in a study of more than 233,000 births in Brooklyn, New York hospitals during the years 1968 to 1979. Anencephaly, myelomeningocele, and hydrocephalus occurred at frequencies of 47.1, 42.4, and 49.3 cases per 100,000 total births, respectively. During the 12 years of the study, the incidence of myelomeningocele decreased at a linear rate of approximately 4.6 cases per 100,000 births per year. A review of comparable reports on births in the northeastern region of the United States shows that a relatively consistent linear decline in myelomeningocele incidence has been proceeding at this rate for the past 50 years. It is concluded that minor local fluctuations and variability in data collection have obscured the steady decrease in occurrence. No significant declines were seen in the incidence rates of anencephaly or hydrocephalus, nor were uniform secular trends for these anomalies evident from previous reports. Epidemiologic differences between myelomeningocele and anencephaly are noted and their common etiology is questioned.

Intracranial developmental cysts in children: treatment by cystoperitoneal shunting.

The author presents the results of primary cystoperitoneal shunting in 12 infants and children with developmental cysts in various intracranial locations. Preoperative studies were done in each child to rule out a brain tumor as the cause of the cyst and to determine whether communication existed between the cyst and the subarachnoid space. The ventricular system was also shunted in children with both noncommunicating cysts and hydrocephalus. Except for 2 children with other operation was needed during a mean follow-up period of 2.2 years. The reasons to recommend shunt insertion as the primary treatment for developmental cysts in children include safety, ease, and a high rate of success compared to attempted excision.

The value of computed tomographic scans in patients with low-risk head injuries.

The determination that a particular head injury is "mild" or "low-risk" is usually made on clinical grounds. Observation at home or in the hospital has been the usual treatment for such patients. A recent report of excessive mortality among these patients with low-risk head injuries in some hospital settings suggests the need for improvement in diagnostic criteria. Our study included 658 patients admitted to Cooper Hospital for a mild head injury, who had a Glasgow Coma Scale score of 13 to 15 on admission, and who experienced a brief loss of consciousness or amnesia after the injury. Their records and cranial computed tomographic (CT) scans on admission were reviewed to determine their subsequent course. In 18% of patients abnormalities were seen on the initial CT scan and 5% required surgery. Among the 62 patients with a Glasgow Coma Scale score of 13, 40% had abnormalities on the CT scan and 10% required surgery. None of the 542 patients with normal CT scans on admission showed subsequent deterioration and none needed surgery. These figures suggest that history and physical examination alone are not adequate to assess head injury or severity of risk and that the addition of a CT scan greatly improves patient assessment. Abnormalities on CT scans are so common in patients with a Glasgow Coma Scale score of 13 that head injuries in these patients should be classified as "moderate" rather than "mild" in severity and risk. Patients with normal CT scans should be considered for observation at home, allowing hospital personnel to devote full attention to the more seriously injured patients.

Delayed and progressive brain injury in closed-head trauma: radiological demonstration.

The importance of delayed or secondary brain insults in the eventual outcome of closed-head trauma has been documented in experimental models. To understand this phenomenon in the clinical setting, we studied a series of head-injured patients in whom multiple cranial computed tomographic (CT) scans were obtained. Patients whose follow-up CT studies revealed new intracranial lesions or worsening, compared with admission findings, were considered to have delayed cerebral injury. One hundred forty-nine (44.5%) of 337 consecutively studied patients developed delayed brain injury. There were highly significant associations (P < 0.001) between the appearance of delayed cerebral insults and the severity of the initial brain injury, the need for cardiopulmonary resuscitation in the field, the presence of coagulopathy at admission, and subdural hematoma on the initial CT scan. In addition, delayed injury was associated (P < 0.001) with higher mortality, slowed recovery, and poorer outcome at 6 months. Delayed brain injury was not significantly associated with patient age, sex, injury mechanism, associated injury, the need for endotracheal intubation in the field, early talking, CT abnormality other than intracranial hematoma, or type of residual neurological deficits. We used multiple regression analysis to explore the relationship between severity of injury, delayed insults, and outcome. As expected, the severity of the initial brain trauma contributed significantly to neurological outcome. The presence of delayed cerebral injury makes the outcome dramatically worse for each category of initial injury severity. The relationship between initial and secondary brain injury is discussed.

Toxic substances in spinal cord injury.

Several investigators have implicated norepinephrine and other toxic substances released in the region of a spinal cord injury in the genesis of the progressive pathological and clinical changes that follow spinal trauma. To test this hypothesis, we subjected cats to T-10 to T-12 laminectomy and monitored epidural spinal evoked potentials from sciatic nerve stimulation. The spinal subarachnoid space was perfused with normal saline, with norepinephrine solution, or with heparinized autologous blood or the pial surface of the spinal cord was exposed to macerated gray matter taken from the upper cervical cord. During 1- to 2-hour exposure periods, we noted no significant changes in the base line spinal evoked potentials. In another series of cats, we have shown that norepinephrine perfused over the spinal cord in this manner diffuses rapidly into the subpial white matter. Therefore, its failure to affect spinal evoked potentials does not represent a failure to penetrate the spinal cord. Putative toxins must originate either in extravasated blood or damaged neural tissue in the region of the spinal cord injury. The failure of ascending spinal tracts to react to blood or cord tissue in our experiment suggests that toxins are not involved in the spinal cord dysfunction that occurs soon after injury.

Delayed brain injury after head trauma: significance of coagulopathy.

We reviewed the records of 253 patients with head injury who required serial computed tomographic (CT) scans; 123 (48.6%) developed delayed brain injury as evidenced by new or progressive lesions after a CT scan. An abnormality in the prothrombin time, partial thromboplastin time, or platelet count at admission was present in 55% of the patients who showed evidence of delayed injury, and only 9% of those whose subsequent CT scans were unchanged or improved from the time of admission (P less than 0.001). Among patients developing delayed injury, mean prothrombin time at admission was significantly longer (14.6 vs. 12.6 s, P less than 0.001) and partial thromboplastin time was significantly longer (36.9 vs. 29.2 s, P less than 0.001) than patients who did not have delayed injury. If coagulation studies at admission were normal, a patient with head injury had a 31% risk of developing delayed insults. This risk rose to almost 85% if at least one clotting test at admission was abnormal (P less than 0.001). We conclude that clotting studies at admission are of value in predicting the occurrence of delayed injury. If coagulopathy is discovered in the patient with head injury early follow-up CT scanning is advocated to discover progressive and new intracranial lesions that are likely to occur.

Moderate head injury: a guide to initial management.

The purpose of this study is to determine the initial treatment of patients who appear to have sustained moderate head injuries when first evaluated. The authors reviewed the records of 341 patients whose initial Glasgow Coma Scale (GCS) scores ranged from 9 to 12, as well as another 106 patients with GCS scores of 13. All patients underwent cranial computerized tomography (CT) at the time of admission. In 40.3% of these patients the CT scans were abnormal (30.6% had intracranial lesions), and 8.1% required neurosurgical intervention (craniotomies for hematoma in 12, elevation of depressed fractures in five, and insertion of intracranial pressure monitors in 19). Four patients died of their intracranial injuries. A similar incidence of lesions found on CT and at surgery suggests that an initial GCS score of 13 be classified with the moderate head injury group. Skull fractures were found to be poor indicators of intracranial abnormalities. These results suggest that all patients with head injury thought to be moderate on initial examination be admitted to the hospital and undergo urgent CT scanning. Patients with intracranial lesions require immediate neurosurgical consultation, surgery as needed, and admission to a critical-care unit. Scans should be repeated in patients whose recovery is less rapid than expected and in all patients with evidence of clinical deterioration; this was necessary in almost half of the patients in this group, and 32% were found to have progression of radiological abnormalities on serial CT scans.

A noninvasive approach to quantitative measurement of flow through CSF shunts. Technical note.

A method of measuring flow rate through cerebrospinal fluid (CSF) shunts is reported. It consists of two thermistors in series applied to the skin over the shunt tubing. The thermistors respond by a drop in measured temperature following application of an ice cube placed on the skin overlying the proximal shunt tube. The time required for the thermal response to travel between the two thermistors is related to the velocity of flow through the shunt tubing. Flow rate can then be calculated using the internal diameter of the tubing. A series of animal experiments employing a constant infusion of mock CSF through subcutaneously implanted shunt tubing showed excellent correlation between calculated flow rates and actual infusion rates. The device is noninvasive and easily adapted to use in patients. The measurements are readily repeatable.

Development of cerebellar malignant astrocytoma at site of a medulloblastoma treated 11 years earlier. Case report.

A child treated for a desmoplastic medulloblastoma of the left cerebellar hemisphere at the age of 10 months developed a malignant astrocytoma in the same site 11 years later. Theories of origin of the second tumor, particularly in relation to concepts of the genesis of medulloblastoma in general, are discussed.

Vancomycin and rifampin therapy for Staphylococcus epidermidis meningitis associated with CSF shunts: report of three cases.

Three patients with Staphylococcus epidermis meningitis associated with cerebrospinal fluid (CSF) shunt devices were treated with a combination of intravenous vancomycin and oral rifampin. Two of the isolates were methicillin-resistant. All patients had a favorable clinical response. Time-kill curves showed that the addition of rifampin to vancomycin resulted in enhanced bactericidal activity against all isolates when compared to either antibiotic alone. This finding suggests that the combination of oral rifampin and intravenous vancomycin may be useful in the treatment of methicillin-resistant and recalcitrant methicillin-sensitive S. epidermis meningitis associated with CSF shunts. In vitro susceptibility testing should be performed.

Laparoscopic L5-S1 diskectomy: a cost-effective, minimally invasive general surgery--neurosurgery team alternative to laminectomy.

Laparoscopic L5-S1 diskectomy (LLD) is a promising new technique for managing disabling pain from herniated lumbar disks. It is unknown, however, whether the clinical results of LLD are superior to those of traditional laminectomy (LAM). This study was undertaken, therefore, in order to compare LLD and LAM in the management of L5-S1 disk herniation unresponsive to conservative treatment measures. Clinical records of 22 patients who underwent 23 LLD procedures and of 23 LAM patients were reviewed with respect to demographics and median age, operative blood loss, operative time, hospital stay, and time of rehabilitation to work/normal activity, as well as postoperative morbidity, recurrent symptoms, long-term functional status, and inhospital patient charges. Two LLD patients had undergone LAM previously, and one had a percutaneous microdiskectomy. All LLD patients had relief of disk pain immediately after surgery. Morbidity after LLD included transient brachial plexus neuropraxia (1), urinary retention (1), and rectus hematoma (1). No LAM complications were reported. Among LLD patients, compared with LAM, median age (34.5 years versus 40 years), estimated blood loss (12 mL versus 68 mL), hospital length of stay (1 day versus 3 days), time to normal activity (17 days versus 79 days) and mean inhospital patient charges ($5,737 +/- 283 versus $7,762 +/- 662) were reduced significantly (P < 0.05). LLD operating time was significantly longer than LAM (210 versus 160 minutes median, P < 0.01). With a median follow-up time of 11.0 months (range, 2 to 23 months) all LLD patients had returned to normal activity, whereas 7 of the LAM group (30%) remained disabled (P < 0.01). Sixty-eight per cent of LLD patients were pain-free during follow-up, compared with 39 per cent of the LAM group (P < 0.05). Sixty-four per cent of LLD patients and 57 per cent of the LAM group needed postoperatively physical therapy. One LLD and 4 LAM patients required reoperation, by LLD and LAM, respectively, for recurrent disk herniation. LLD is a safe, cost-effective, minimally invasive operation for managing disabling L5-S1 disk herniation. Compared with LAM, LLD reduces blood loss, length of stay, rehabilitation time, and patient charges, and improves long-term functional and pain-free status. LLD should be considered as an alternative to LAM for patients with herniated L5-S1 intervertebral disks unresponsive to conservative management.

Brief history of surgical timing: surgery for ruptured intracranial aneurysms.

The neurosurgical profession has taken a circuitous route to attain its current knowledge about timing for aneurysm surgery. While addressing the timing issue, neurosurgeons were beset by many pressures simultaneously. They were forced to justify not only optimal surgical techniques but the need for surgery at all in the treatment of ruptured aneurysms. The beliefs of surgeons with strong personalities, in addition to intuitive guesses, often served to guide surgery in the absence of scientific evidence. That any progress could be made against a background of desperately ill patients and frustrating early results is remarkable. The author briefly outlines the controversies and misdirection that accompanied this progress toward understanding surgical timing in the treatment of ruptured aneurysms.

Laminectomy compared with laparoscopic diskectomy and outpatient laparoscopic diskectomy for herniated L5-S1 intervertebral disks.

The objective of this study was to evaluate the clinical efficacy and cost effectiveness of inpatient and outpatient laparoscopic lumbar diskectomy (LLD) compared with laminectomy (LAM) in the surgical treatment of disabling L5-S1 disk herniation. Sixty-two adults underwent surgery for herniated L5-S1 intervertebral disks (31 LLD and 31 LAM). Operative blood loss (EBL) (milliliters), operative time (ORT) (minutes), hospital stay (LOS), and rehabilitation time to normal activity (REHAB) (days), recurrent symptoms, postoperative morbidity, percent pain free, and hospital patient charges were calculated. Thirty LLD patients (97%) had immediate relief of disk pain. Morbidity after LLD included transient urinary retention (one) and rectus hematoma (one). One LAM patient had a pseudomeningocele. Among patients observed for > or =6 months, with a median follow up time of 34 months, 22 of 25 LLD patients (88%) returned to normal activity, while 12 of the LAM group (52%) were disabled (p = 0.004). Functional outcome was improved by LLD for workers compensation patients followed > or =6 months, with 86% LAM disabled, vs. 10% LLD (p = 0.001). Sixteen LLD patients (52%) and 18 (58%) of the LAM group needed postoperative physical therapy. Four LLD patients recurred; three required reoperation. Four LAM patients had surgery for recurrent disk herniation. ORT was longer for LLD than LAM (210 vs. 158 minutes, median, p < 0.05). EBL and REHAB time were significantly reduced with LLD, vs. LAM. With a median follow-up of 34 months, 58% of LLD and 39% of LAM patients followed > or =6 months were pain free. Outpatient LLD (n = 9) reduced LOS (1 day vs. 2 days and 4 days, p < 0.01) and lowered patient charges ($4,405 vs. $5,723 and $7,192, p < 0.01) compared with inpatient LLD (n = 23) and LAM, respectively. LLD is a safe, cost-effective, minimally invasive alternative to LAM for treating herniated L5-S1 disks. Compared with LAM, LLD reduces EBL, LOS, REHAB time, and patient charges, improves function, and increases long-term pain relief. Cost effectiveness is optimized when LLD is performed as outpatient surgery.