Reversal of delayed-onset paraplegia after thoracic aortic surgery with cerebrospinal fluid drainage

We report two patients who had postoperative reversal of delayed-onset paraplegia after cerebrospinal fluid (CSF) drainage after type I thoracoabdominal aneurysm repair. CSF drainage was not initiated before operation because of the urgent presentation of both patients. Decompression of the spinal canal by CSF drainage may improve spinal cord circulation in certain patients and may avoid or decrease neurologic injury. In view of the low morbidity of this intervention, we recommend routine CSF drainage during elective repair of thoracic and thoracoabdominal aneurysms. (J VASC SURG 1994;20:315-7.)     

Remodeling of cerebrospinal fluid lipoprotein particles after human traumatic brain injury

The association between possession of the APOE epsilon4 allele and unfavourable outcome after traumatic brain injury (TBI) suggests that the apolipoprotein E protein (apoE) plays a key role in the response of the human brain to injury. ApoE is known to regulate cholesterol metabolism in the periphery through its action as a ligand for receptor mediated uptake of lipoprotein particles (Lps). Greater understanding of cholesterol metabolism in the human central nervous system may identify novel treatment strategies applicable to acute brain injury. We report findings from the analysis of lipoproteins in the cerebrospinal fluid (CSF) of patients with TBI and non-injured controls, testing the hypothesis that remodeling of CSF lipoproteins reflects the response of the brain to TBI. CSF Lps were isolated from the CSF of controls and patients with severe TBI by size exclusion chromatography, and the lipoprotein fractions analysed for cholesterol, phospholipid, apoAI, and apoE. There was a marked decrease in apoE containing Lps in the TBI CSF compared to controls (p=0.002). After TBI there was no significant decrease in apoAI containing CSF Lps (CSF LpAI), but the apoAI resided on smaller sized particles than in control CSF. There was a population of very small sized Lps in TBI CSF, which were associated with the increased cholesterol (p=0.0001) and phospholipid (p=0.040) seen after TBI. The dramatic loss of apoE containing Lps from the CSF, and the substantial increase in CSF cholesterol, support the concept that apoE and cholesterol metabolism are intimately linked in the context of acute brain injury. Treatment strategies targeting CNS lipid transport, required for neuronal sprouting and synaptogenesis, may be applicable to traumatic brain injury.     

Vascular endothelial growth factor is increased in cerebrospinal fluid after traumatic brain injury in infants and children

OBJECTIVE: Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis, the formation of which is triggered by hypoxia, cytokines, and growth factors and is also induced by activation of the adenosine 2B receptor. VEGF is neuroprotective in several models of experimental brain injury and is increased in brain after traumatic brain injury (TBI) in humans and experimental animals. Adenosine is a neuroprotective purine metabolite that increases in cerebrospinal fluid (CSF) after clinical TBI in children. We hypothesized that VEGF levels would 1). be increased in CSF after TBI in infants and children, and 2). be preceded by increases in CSF adenosine. To test this hypothesis, we designed a case-control study to compare the CSF of infants and children after severe TBI with that of uninjured children. METHODS: Using an Institutional Review Board-approved protocol, we compared CSF concentrations of VEGF (by enzyme-linked immunosorbent assay) and adenosine (by high-performance liquid chromatography) in 73 samples from 14 infants and children with severe TBI (Glasgow Coma Scale score 相似文献   

Increase in the chronically monitored cerebrospinal fluid pressure after experimental brain injury in rats

The early effects of experimental brain injury with diffuse axonal lesions on intracranial pressure (ICP), mean arterial pressure (MAP) and cerebral perfusion pressure (CPP) in rats have been already studied. The aim of this experiment was to examine the effects of brain injury on ICP, MAP and CPP during the first few days post-injury. In order to do that, an accurate technique of ICP measurement had to be developed. In a series of eight rats, a translumbar intrathecal catheter (TIC) was surgically introduced allowing repeated measurements of cerebrospinal fluid pressure (CSFP). Under anaesthesia, a second series of nine rats were equipped simultaneously with TIC and an intracranial fiberoptic device to measure ICP. Simultaneous measurements of CSFP and ICP were recorded for baseline values, than during and after jugular compression which was intended to induce an acute and significant increase in ICP. A third series of 53 rats having TIC received an experimental severe brain injury. MAP was measured non-invasively and CPP was calculated as CPP MAP. CSFP, MAP and CPP were intermittently measured during 5-6 post-traumatic days and compared to the values obtained during ten control rats (SHAM). A clinical score was used to compare clinical condition. The results showed that the translumbar CSFP accurately measured ICP in rats having normal or acutely increased ICP. The experimental brain injury induced increased CSFP lasting up to 5-6 days, with increased MAP during the first 6hours. CPP values were compromised at 24-48hours. The clinical performance was reduced in the brain injured rats. The translumbar technique of CSFP measurement reflected exact ICP in normal and acutely increased ICP in rats. Experimental brain injury with diffuse axonal lesions can increase lumbar CSFP in rats for many days.     

Treatment of delayed-onset neurological deficit after aortic surgery with lumbar cerebrospinal fluid drainage

OBJECTIVE: The phenomenon of delayed neurological deficit after thoracoabdominal aortic aneurysm repair was first reported in the late 1980s. The mechanism may be reduced collateral circulation during periods of hypotension, cord edema, or reperfusion injury. Few patients with delayed-onset neurological deficit have recovered from this devastating complication. The experience with six patients treated with lumbar cerebrospinal fluid (CSF) drainage is reported. METHODS: Five patients underwent thoracoabdominal aortic aneurysm repair. Before and immediately after the operation, the patients exhibited no abnormalities in motor or sensory function. Patients presented between 12 and 40 hours postoperatively with rapid motor and sensory loss in their lower extremities. Hypotensive events immediately preceded the onset of deficit in five patients. The sixth patient experienced an acute onset of back pain and was found to have thrombus without evidence of dissection in the descending aorta. RESULTS: Patients were treated with volume expansion and vasoactive drugs to achieve a mean arterial pressure of more than 70 mm Hg. Lumbar CSF drainage was instituted promptly in four patients; all displayed marked neurological improvement. Two patients underwent CSF drainage several hours after the onset of symptoms and did not improve. The duration of CSF drainage ranged from 15 to 72 hours, with a goal of maintaining the lumbar CSF pressure at less than 10 mm Hg. CONCLUSION: The efficacy of CSF drainage may relate to reducing CSF pressure, which may increase spinal cord perfusion. Rapid initiation of CSF drainage with aggressive support of blood pressure may result in neurological improvement in some patients.     

Naloxone lowers cerebrospinal fluid levels of excitatory amino acids after thoracoabdominal aortic surgery

OBJECTIVE: Although naloxone has been used to prevent ischemic spinal cord injury (SCI), its effect on excitatory amino acids (EAAs) has not been understood. We investigated the clinical significance of naloxone by measuring EAAs in the cerebrospinal fluid (CSF) in patients undergoing thoracoabdominal aortic surgery. METHODS AND SUBJECTS: Twenty-seven patients (15 men and 12 women; mean age, 66 +/- 12 years) undergoing prosthetic replacement of the thoracoabdominal aorta (n = 19) or the descending thoracic aorta (n = 8) from April 1997 to June 2003 under distal perfusion and mild hypothermia were enrolled in this cohort study with historical controls. Their etiology was 7 dissections and 20 nondissections. In 16 patients (naloxone group), intravenous infusion of naloxone (1 microg/kg/h) was continued until the patients became alert. In the remaining 11 patients (control group) naloxone was not given. CSF drainage was used in all patients. CSF levels of EAAs, glutamate, aspartate, and glycine were measured at 6 points in time until 72 hours postoperatively, using a high-performance liquid chromatography method. RESULTS: In 5 patients with SCI (2 patients in control group, 3 in naloxone group), CSF levels of glutamate and glycine continued to increase even at 72 hours postoperatively, and were significantly more elevated than those in patients without SCI ( P < .0001, glutamate; P = .0006, glycine). Postoperative maximum levels of CSF glutamate and glycine were also significantly higher in patients with postoperative SCI than in patients without SCI (glutamate: 215.3% +/- 158.6% vs 32.9% +/- 37.3% increase from baseline, P < .0001; glycine: 309.1% +/- 218.2% vs 89.2% +/- 103.1% increase from baseline, P = .0036). CSF levels of glutamate and aspartate in naloxone group were significantly lower than those in control group ( P = .0161, glutamate; P < .0001, aspartate). Postoperative maximum level of CSF aspartate was also significantly lower in the naloxone group than in the control group (8.3% +/- 75.5% vs 119.7% +/- 120.6% increase from baseline, P = .0077). In multivariate logistic regression analysis, postoperative maximum CSF glutamate >100% from baseline ( P < .001) and postoperative maximum level of CSF glycine ( P = .005)were identified as the independent risk factors for SCI. Both SCI ( P < .001) and postoperative maximum level of CSF glycine ( P = .005) were the independent predictors for postoperative maximum level of CSF glutamate >100% from baseline. CONCLUSIONS: CSF levels of EAAs are elevated in patients with SCI. CSF glutamate is the strongest independent predictor of SCI. Naloxone is effective in lowering CSF levels of EAAs.     

Increased adrenomedullin in cerebrospinal fluid after traumatic brain injury in infants and children

Adrenomedullin is a recently discovered 52-amino acid peptide that is a potent vasodilator and is produced in the brain in experimental models of cerebral ischemia. Infusion of adrenomedullin increases regional cerebral blood flow and reduces infarct volume after vascular occlusion in rats, and thus may represent an endogenous neuroprotectant. Disturbances in cerebral blood flow (CBF), including hypoperfusion and hyperemia, frequently occur after severe traumatic brain injury (TBI) in infants and children. We hypothesized that cerebrospinal fluid (CSF) adrenomedullin concentration would be increased after severe TBI in infants and children, and that increases in adrenomedullin would be associated with alterations in CBF. We also investigated whether posttraumatic CSF adrenomedullin concentration was associated with relevant clinical variables (CBF, age, Glasgow Coma Scale [GCS] score, mechanism of injury, and outcome). Total adrenomedullin concentration was measured using a radioimmunometric assay. Sixty-six samples of ventricular CSF from 21 pediatric patients were collected during the first 10 days after severe TBI (GCS score < 8). Control CSF was obtained from children (n = 10) undergoing lumbar puncture without TBI or meningitis. Patients received standard neurointensive care, including CSF drainage. CBF was measured using Xenon computed tomography (CT) in 11 of 21 patients. Adrenomedullin concentration was markedly increased in CSF of infants and children after severe TBI vs control (median 4.5 versus 1.0 fmol/mL, p < 0.05). Sixty-two of 66 CSF samples (93.9%) from head-injured infants and children had a total adrenomedullin concentration that was greater than the median value for controls. Increases in CSF adrenomedullin were most commonly observed early after TBI. CBF was positively correlated with CSF adrenomedullin concentration (p < 0.001), but this relationship was not significant when controlling for the effect of time. CSF adrenomedullin was not significantly associated with other selected clinical variables. We conclude adrenomedullin is markedly increased in the CSF of infants and children early after severe TBI. We speculate that adrenomedullin participates in the regulation of CBF after severe TBI.     

Mixed venous oxygen saturation is a prognostic marker after surgery for aortic stenosis

Background: Adequate monitoring of the hemodynamic state is essential after cardiac surgery and is vital for medical decision making, particularly concerning hemodynamic management. Unfortunately, commonly used methods to assess the hemodynamic state are not well documented with regard to outcome. Mixed venous oxygen saturation (SvO₂) was therefore investigated after cardiac surgery. Methods: Detailed data regarding mortality were available on all patients undergoing aortic valve replacement for isolated aortic stenosis during a 5‐year period in the southeast region of Sweden (n=396). SvO₂ was routinely measured on admission to the intensive care unit (ICU) and registered in a database. A receiver operating characteristics (ROC) analysis of SvO₂ in relation to post‐operative mortality related to cardiac failure and all‐cause mortality within 30 days was performed. Results: The area under the curve (AUC) was 0.97 (95% CI 0.96–1.00) for mortality related to cardiac failure (P=0.001) and 0.76 (95% CI 0.53–0.99) for all‐cause mortality (P=0.011). The best cutoff for mortality related to cardiac failure was SvO₂ 53.7%, with a sensitivity of 1.00 and a specificity of 0.94. The negative predictive value was 100%. The best cutoff for all‐cause mortality was SvO₂ 58.1%, with a sensitivity of 0.75 and a specificity of 0.84. The negative predictive value was 99.4%. Post‐operative morbidity was also markedly increased in patients with a low SvO₂. Conclusion: SvO₂, on admission to the ICU after surgery for aortic stenosis, demonstrated excellent sensitivity and specificity for post‐operative mortality related to cardiac failure and a fairly good AUC for all‐cause mortality, with an excellent negative predictive value.     

Alterations in cerebrospinal fluid apolipoprotein E and amyloid beta-protein after traumatic brain injury

There is evidence that apolipoprotein E (apoE) and amyloid beta-protein (Abeta), which are implicated in the pathology of chronic neurodegenerative disorders, are involved in the response of the brain to acute injury; however, human in vivo evidence is sparse. We conducted a prospective observational study to determine the magnitude and time-course of alterations in cerebrospinal fluid (CSF) apoE and Abeta concentrations after traumatic brain injury (TBI), and the relationship of these changes to severity of injury and clinical outcome. Enzyme linked immunosorbant assay (ELISA) was used to assay apoE, Abeta(1-40) and Abeta(1-42) in serial CSF samples from 13 patients with TBI and 13 controls. CSF S100B and tau were assayed as surrogate markers of brain injury. There was a significant decrease in CSF apoE (p < 0.001) and Abeta (p< 0.001) after TBI contrasting the observed elevation in CSF S100B (p < 0.001) and tau (p < 0.001) concentration. There was significant correlation (r = 0.67, p = 0.01) between injury severity and the decrease in Abeta(1-40) concentration after TBI. In vivo, changes in apoE and Abeta concentration occur after TBI and may be important in the response of the human brain to injury.     

Assessment of the macrophage marker quinolinic acid in cerebrospinal fluid after pediatric traumatic brain injury: insight into the timing and severity of injury in child abuse

This study measured quinolinic acid (QUIN), a macrophage-microglia derived neurotoxin, in the cerebrospinal fluid (CSF) of children after non-inflicted and inflicted traumatic brain injury (nTBI, iTBI), and correlated QUIN concentrations with age, mechanism of injury (nTBi vs. iTBI), Glasgow Coma Scale (GCS) score and 6-month Glasgow Outcome Score. One hundred fifty-two CSF samples were collected from 51 children with severe TBI (GCS < or = 8). CSF was collected at the time an intraventricular catheter was placed and daily thereafter. QUIN concentration was measured by gas chromatography-mass spectroscopy. Patients ranged in age from 2 months to 16 years. Eleven children (22%) had iTBI. Initial and peak CSF QUIN concentrations were higher in patients with iTBI versus nTBI after adjusting for time after injury and GCS. Despite the lack of a history of trauma in 82% of children with iTBI, 100% had a peak QUIN concentration of >100 nM. There was a significant increase in the CSF concentrations of QUIN following severe nTBI and iTBI in children. Higher initial and peak QUIN concentrations after iTBI may be due to severity of injury, young age, and/or delay in seeking medical care, which allows for increased secondary injury.     

Clinical significance of alphaII-spectrin breakdown products in cerebrospinal fluid after severe traumatic brain injury

Following traumatic brain injury (TBI), the cytoskeletal protein alpha-II-spectrin is proteolyzed by calpain and caspase-3 to signature breakdown products. To determine whether alpha -II-spectrin proteolysis is a potentially reliable biomarker for TBI in humans, the present study (1) examined levels of spectrin breakdown products (SBDPs) in cerebrospinal fluid (CSF) from adults with severe TBI and (2) examined the relationship between these levels, severity of injury, and clinical outcome. This prospective case control study enrolled 41 patients with severe TBI, defined by a Glasgow Coma Scale (GCS) score of < or =8, who underwent intraventricular intracranial pressure monitoring. Patients without TBI requiring CSF drainage for other medical reasons served as controls. Ventricular CSF was sampled from each patient at 6, 12, 24, 48, 72, 96, and 120 h following TBI and analyzed for SBDPs. Outcome was assessed using the Glasgow Outcome Score (GOS) 6 months after injury. Calpain and caspase-3 mediated SBDP levels in CSF were significantly increased in TBI patients at several time points after injury, compared to control subjects. The time course of calpain mediated SBDP150 and SBDP145 differed from that of caspase-3 mediated SBDP120 during the post-injury period examined. Mean SBDP densitometry values measured early after injury correlated with severity of injury, computed tomography (CT) scan findings, and outcome at 6 months post-injury. Taken together, these results support that alpha -II-spectrin breakdown products are potentially useful biomarker of severe TBI in humans. Our data further suggests that both necrotic/oncotic and apoptotic cell death mechanisms are activated in humans following severe TBI, but with a different time course after injury.     

Appraisal of cerebrospinal fluid alterations during aortic surgery with intrathecal papaverine administration and cerebrospinal fluid drainage

We have previously described a technique for intrathecal administration of papaverine and cerebrospinal fluid drainage to prevent paraplegia after aortic surgery. Herein we report the cerebrospinal fluid and hemodynamic alterations that occurred in 11 patients who had 30 mg of a specially prepared papaverine hydrochloride 10% dextrose solution injected before aortic cross-clamping and also had cerebrospinal fluid drainage. A mean of 26.6 ml (SD +/- 7.1 ml) was drained before and 34.6 ml (SD +/- 24.1 ml) was drained during aortic cross-clamping. The cerebrospinal fluid pressure increased significantly with anesthetic induction (p less than 0.03), during the period between anesthetic induction and cerebrospinal fluid drainage (p less than 0.005), and with aortic cross-clamping (p less than 0.05). These cerebrospinal fluid pressure alterations were similar to central venous pressure increases with a significant linear correlation between cerebral spinal fluid pressure and central venous pressure before anesthetic induction (r2 = 0.81, p less than 0.005), and both before (r2 = 0.94, p less than 0.005) and after (r2 = 0.74, p less than 0.005) aortic cross-clamping. As expected, cerebrospinal fluid pressure was significantly reduced by cerebrospinal fluid drainage before aortic cross-clamping (p less than 0.001). The administration of intrathecal papaverine had no significant effect on mean arterial pressure, systemic vascular resistance, cerebrospinal fluid pressure, nor the pH of cerebrospinal fluid. Neither were there any complications noted related to the technique. All the patients survived, and no new immediate postoperative paraparesis or paraplegia occurred.(ABSTRACT TRUNCATED AT 250 WORDS)