Continuous Cerebrospinal Fluid Research Articles

Demographic Factors Influence Cognitive Recovery After Shunt for Normal-Pressure Hydrocephalus

Several studies have reported that ventriculoperitoneal shunt insertion for treatment of normal-pressure hydrocephalus results in improvement of gait and, less frequently, improvement of cognition. We sought to identify the demographic factors associated with cognitive improvement after shunt insertion to improve assessment of prognosis for cognitive gains with treatment. We report cognitive testing before and after ventriculoperitoneal shunt insertion in 36 patients with normal pressure hydrocephalus, who previously had improvement of any clinical symptom--gait, urinary incontinence, cognition--after a diagnostic trial of continuous cerebrospinal fluid drainage. One third of patients met our definition of good cognitive improvement: improvement by at least 25% on at least half of the cognitive tests administered. There was a significant negative linear relationship between age and probability of good cognitive improvement. Additionally, the degree of cognitive improvement was found to be greater in women than men (P = 0.002). Age was found to be a better predictor of improvement on memory tests, while sex was a better predictor of improvement on non-memory tests after shunt insertion.

The Effect of Autologous Fibrin Tissue Adhesive on Postoperative Cerebrospinal Fluid Leak in Spinal Cord Surgery: A Randomized Controlled Trial

A prospective randomized study evaluating the efficacy of autologous fibrin tissue adhesive for decreasing postoperative cerebrospinal fluid (CSF) leak in spinal cord surgery. To compare postoperative CSF leak in 3 groups (i.e., autologous fibrin tissue adhesive used, commercial fibrin glue used, and no fibrin tissue adhesive used) of patients undergoing spinal surgery who needed dural incision. Spinal cord operations, particularly when dural incision is inevitable, sometimes involve postoperative CSF leak. Because CSF leak is a serious complication, countermeasure is necessary to prevent it after dural suture. Commercial fibrin tissue adhesive was formerly used. Because the possibility of prion infection was widely noticed, commercial fibrin tissue adhesive containing animal components has been used less often. In 13 of 39 cases in which dural incision would be made, 400 mL whole blood was drawn, and autologous fibrin tissue adhesive was made of plasma. Cases were divided into 3 groups: (1) dural closure alone, (2) use of autologous fibrin tissue adhesive after dural closure, and (3) use of commercial fibrin tissue adhesive after dural closure. The primary outcome measure was determined as postoperative (3 days) volume of drainage fluid, and results were analyzed using the analysis of variance. The secondary outcome measure was general blood test, coagulation assay, and plasma fibrinogen, and these were analyzed also using the analysis of variance. There was a significant difference in the primary outcome between the autologous and control groups. No complications such as infection or continuous CSF leak were observed in any case. The mean volume of drainage fluid was 586.2 mL in the group with autologous fibrin tissue adhesive and 1026.1 mL in the group without fibrin tissue adhesive. The volume of drainage fluid was significantly lower in the former group than that in the latter group. There was no statistical difference between the volumes of the group with autologous adhesive and with commercial adhesive (639.2 mL). We used autologous fibrin tissue adhesive as a new sealant after dural closure instead of commercial fibrin tissue adhesive. No definitive CSF leak was observed, and the volume of drainage fluid was significantly lower in the group with autologous fibrin tissue adhesive than that in the group without fibrin tissue adhesive. The use of autologous fibrin tissue adhesive was superior to that of commercial fibrin tissue adhesive in cost.

Cerebral blood oxygenation after cerebrospinal fluid removal in hydrocephalus measured by near infrared spectroscopy

Background The cerebrospinal fluid (CSF) tap test has been used for the diagnosis of chronic hydrocephalus to identify the candidates for surgical CSF shunting. However, a high rate of false negative results limits it utility. The purpose of this study is to investigate whether the concomitant monitoring of cerebral hemodynamics by near infrared spectroscopy (NIRS) can improve the diagnostic accuracy of the tap test. Methods Thirteen patients with dilated ventricular system were candidates for this study. We assessed for the patterns of cerebral blood oxygenation (CBO) change in hydrocephalus to determine whether CBO change after CSF removal is useful for selecting shunt candidates. Results Patients who showed clinical improvement following CSF shunting had a characteristic CBO change with increases in the concentration of oxyhemoglobin (Oxy-Hb), and patients without improvement during continuous CSF drainage test showed no increase in Oxy-Hb. Conclusion The current data suggests that CBF increases after CSF removal in hydrocephalus. Although the patients utilized in the present study had secondary chronic hydrocephalus, we speculate that these data could be applied to patients with idiopathic chronic hydrocephalus. Further investigation would be of benefit.

Continuous Versus Intermittent Cerebrospinal Fluid Drainage after Severe Traumatic Brain Injury in Children: Effect on Biochemical Markers

Drainage of cerebrospinal fluid (CSF) is routinely used in the treatment of severe traumatic brain injury (TBI), either continuously or intermittently in response to increases in intracranial pressure (ICP). There has been little study of the effect of CSF drainage method on the biochemistry, pathophysiology or outcome of TBI in adults or children. Having previously reported that a variety of markers of injury or repair increase in CSF after severe TBI, we chose to evaluate directly the effect of CSF drainage method on the biochemistry and volume of CSF drained as well as ICP. We hypothesized that concentrations of these markers would be similar in CSF drained continuously vs intermittently. We compared CSF levels of markers of neuronal injury (neuron specific enolase, [NSE]), glial injury (s100B), inflammation (interleukin-6 [IL-6]), and regeneration (vascular endothelial growth factor [VEGF]) (measured by ELISA) in 80 CSF samples from 19 severely injured children whose CSF was drained continuously (n = 13) versus intermittently (n = 6) as part of standard care in two institutions. Compared to continuous CSF drainage, intermittent drainage of CSF was associated with twofold greater CSF concentrations of NSE, s100B, IL-6 and VEGF (p < 0.05) and with about half the volume of CSF removal than continuous drainage (p = 0.002). The resulting elimination (concentration × volume) of these biochemicals, however, was not influenced by drainage method. Patients treated with continuous drainage had lower mean ICPs than those with intermittent drainage (13.6 ± 0.69 vs. 21.8 ± 0.95 mm Hg, p < 0.0001). We conclude that the method of CSF drainage greatly affects concentrations of CSF markers after TBI and may influence ICP. The influence of method on CSF marker concentration must be kept in mind when interpreting

719 Ventriculoperitoneal Shunting for Idiopathic Normal-pressure Hydrocephalus: Predictors of Treatment Response and Analysis of Long-term Outcomes

INTRODUCTION: Because of the difficulty in distinguishing idiopathic normal-pressure hydrocephalus (INPH) from other neurode-generative conditions unrelated to cerebrospinal fluid (CSF) dynamic pathology, outcome after CSF shunting for presumed INPH remains highly variable. Whereas secondary NPH often responds to shunting, INPH is still considered by most to be an untreatable disease. We set out to elucidate predictors of outcome and characterize long-term outcome after CSF shunting for INPH. METHODS: INPH patients with computed tomography-documented hydrocephalus, normal opening lumbar-puncture CSF pressure, two clinical features of INPH (gait, urinary, or dementia), demonstrating frequent B waves on continuous lumbar CSF pressure monitoring, and improving with 3-day trial of lumbar CSF drainage underwent CSF shunting. Patients were clinically followed up for 1, 3, 6, and 12 months after surgery. RESULTS: One hundred thirty-two patients underwent 179 shunt surgeries; 44 (33%), 79 (60%), and 99 (75%) patients experienced symptomatic improvement 3, 6, and 24 months after shunting. Gait improvement was the first clinical response in 88 patients (93%) responding to CSF shunting. Dementia and urinary incontinence were twofold less likely to improve versus gait abnormalities (RR, 0.49; 95% CI, 0.4–0.9). Radiological evidence of corpus callosum impingement (RR, 1.64; 95% CI, 1.05–2.58), gait pathology as the primary symptom (RR, 1.91; 95% CI, 1.04–3.49), and decreasing duration of INPH symptoms in years (RR, 1.15; 95% CI, 1.04–1.27) were associated with improvement after CSF shunting. In multivariate analysis, duration of symptoms (RR, 0.89; 95% CI, 0.82–0.98) and gait as the primary deficit (RR, 1.87; 95% CI, 1.02–3.43) were independent predictors of outcome after CSF shunting for NPH. CONCLUSION: Shunting INPH patients with B waves on CSF pressure monitoring who improve with 3-day CSF drainage resulted in symptomatic improvement in the majority of cases (75%). Corpus callosum impingement on magnetic resonance imaging, gait abnormalities as the primary symptom, and shorter duration of symptoms predicted improvement with CSF shunting. This series of shunted INPH patients is the largest to date and dispels the notion that INPH is an untreatable disease.

Spinal subdural hematoma: a sequela of a ruptured intracranial aneurysm?

Background A case of spinal subdural hematoma (SSDH) following subarachnoid hemorrhage (SAH) because of a ruptured internal carotid aneurysm is described. Such a case has never been reported. Case description A 52-year-old woman underwent a craniotomy for a ruptured internal carotid aneurysm. A computed tomography scan showed that SAH existed predominantly in the posterior fossa and subdural hematoma beneath the cerebellar tentorium. Intrathecal administration of urokinase, IV administration of fasudil hydrochloride, and continuous cerebrospinal fluid (CSF) evacuation via cisternal drainage were performed as prophylactic treatments for vasospasm. On the sixth postoperative day, the patient complained of severe lower back and buttock pain. Magnetic resonance imaging showed a subdural hematoma in the lumbosacral region. Although the mass effect was extensive, the patient showed no neurologic symptoms other than the sciatica. She was treated conservatively. The hematoma dissolved gradually and had diminished completely 15 weeks later. Her pain gradually subsided, and she was discharged 7 weeks later without any neurologic deficit. Conclusion Although the exact mechanism of SSDH in this case is unclear, we speculate that this SSDH was a hematoma that migrated from the intracranial subdural space. Low CSF pressure because of continuous drainage and intrathecal thrombolytic therapy may have played an important role in the migration of the hematoma through the spinal canal. It is important to recognize the SSDH as a possible complication of the SAH accompanied with intracranial subdural hematoma.

Complications of closed continuous lumbar drainage of cerebrospinal fluid.

Sixty three patients who had a lumbar subarachnoid catheter placed for closed continuous cerebrospinal fluid drainage and the complications are presented. The drain was successful in achieving the desired goal in 59 patients (93,6%). The complications are mainly divided into 3 groups; A - complications related to alterations in CSF drainage rate, B - complications due to mechanical failure of the catheter, C - infection. The overall complication rate is found to be 44,4%. Overdrainage, pneumocephalus and meningitis are found to be the most severe complications, but most of these complications are reversible with early recognition. Unfortunately one patient died following meningitis and hepatic failure. Lumbar subarachnoid drainage is a safe method unless the development of any neurological findings should prompt rapid discontinuation of lumbar drainage and immediate radiographic evaluation.

Cerebrospinal fluid procalcitonin and severe traumatic brain injury in children.

To determine the relationship between cerebrospinal fluid procalcitonin concentration and severe traumatic brain injury in children. Prospective, observational clinical study. A multidisciplinary, tertiary-care pediatric intensive care unit. Twenty-eight patients who required external ventricular drainage for management of severe traumatic brain injury (Glasgow Coma Scale score of <8) and 22 control patients for whom lumbar cerebrospinal fluid evaluation excluded possible meningitis. Standard intracranial pressure-directed neurointensive care, including intraventricular catheter placement and continuous cerebrospinal fluid drainage, was used to manage patients with severe traumatic brain injury. Demographic data including age, mechanism of injury, time of injury, initial Glasgow Coma Scale score, and outcome were collected. Cerebrospinal fluid procalcitonin concentration was determined by immunoluminometric assay. Initial cerebrospinal fluid procalcitonin concentration (median [range]) in patients with severe traumatic brain injury was increased greater than three-fold vs. controls (0.41 ng/mL [0.15-2.14] vs. 0.12 ng/mL [0.00-0.24], p <.001). Initial cerebrospinal fluid procalcitonin concentration among patients with abusive head trauma (0.31 ng/mL [0.29-0.50]) also was increased vs. controls (p <.05), although this increase was less robust than patients with accidental trauma (0.41 ng/mL [0.15-2.14], p <.001 vs. controls). Additional examination of key demographic and outcome variables with a generalized linear regression model was performed for patients with severe traumatic brain injury. Univariate analysis revealed that both time after injury (p <.01) and abusive head trauma as a mechanism of injury (p <.001) were associated with attenuation of the increased cerebrospinal fluid procalcitonin response after traumatic brain injury. Cerebrospinal fluid procalcitonin concentration is increased in children after traumatic brain injury. The attenuated increase in cerebrospinal fluid procalcitonin among victims of abusive head trauma warrants further study because it may reflect impairment of endogenous neuroprotective mechanisms or delay in seeking medical attention. The significance of these observations remains to be determined as future studies elucidate the physiologic and mechanistic properties of procalcitonin.

Thoracic and thoracoabdominal aortic aneurysm repair: Use of evoked potential monitoring in 118 patients

Purpose: Paraplegia is the most dreaded and severe complication of surgery on the descending thoracic aorta (TAA) and thoracoabdominal aorta (TAAA). The functional integrity of the spinal cord can be monitored by means of intraoperative recording of myogenic-evoked responses after transcranial electrical stimulation (tcMEP) and somatosensory-evoked potential (SEP) monitoring. In this study, we evaluated the results of evoked potential monitoring and the adequacy of the strategy followed. Method: The spinal cord of 118 patients (78 men; age, 65 ± 12 years; 79 TAAAs, 39 TAAs) undergoing surgery on the TAA or TAAA was monitored with tcMEP and SEP. Spinal cord protection was achieved by means of a multimodality approach: moderate hypothermia (32°C rectal temperature), continuous cerebrospinal fluid drainage to keep the pressure less than 10 mm Hg, reimplantation of intercostal arteries, left ventricular bypass grafting, and staged clamping. In the case of evoked potential changes more than 50% of baseline, the strategy was adjusted: reattachment of more segmental arteries when technically feasible, higher distal and proximal perfusion pressures, and enhanced cerebrospinal fluid drainage. Results: Forty-two of 118 patients (35.6%) had a more than 50% of baseline tcMEP reduction during cross-clamping. At this point, only 5 of those 42 cases were also associated with SEP reduction of more than 50% of baseline. On the basis of the tcMEP findings, the strategy was adjusted. Five patients had postoperative paraplegia (4.2%). Conclusion: tcMEP monitoring seems to be a useful adjunct of the protective techniques and may cause substantial adjustments in strategy, reducing the incidence of postoperative paraplegia. (J Vasc Surg 2001;34:1035-40.)

Therapy of malignant intracranial hypertension by controlled lumbar cerebrospinal fluid drainage.

To evaluate the effect of controlled lumbar cerebrospinal fluid drainage in adult patients with refractory intracranial hypertension. Prospective, pre- vs. postintervention study. Surgical intensive care unit of a university hospital. Twenty-three patients with severe traumatic brain injury or delayed ischemia after subarachnoid hemorrhage with intracranial hypertension refractory to aggressive treatment, including repeated applications of tromethamine, hypertonic saline solution, barbiturate coma, and decompressive craniectomy. Patients were considered for controlled lumbar cerebrospinal fluid drainage if basal cisterns on computerized tomography scan were discernible. After institution of a lumbar drain, cerebrospinal fluid was gradually aspirated, and then, continuous cerebrospinal fluid drainage was maintained under control of intracranial pressure (ICP) and pupillary status. ICP and cerebral perfusion pressure before and after initiation of lumbar cerebrospinal fluid drainage and related complications were documented. The neurologic outcome of the patients was assessed according to the Glasgow Outcome Scale 6 months after injury. As a result of lumbar cerebrospinal fluid drainage, all patients demonstrated an immediate and lasting decrease of ICP and a concomitant increase of cerebral perfusion pressure. Two patients temporarily showed a unilateral fixed and dilated pupil 6 and 8 hrs after onset of lumbar cerebrospinal fluid drainage, respectively. Ten patients showed a favorable outcome, four patients survived with a severe permanent neurologic deficit, one patient remained in a persistent vegetative state, and eight patients died. Controlled lumbar cerebrospinal fluid drainage significantly reduces refractory intracranial hypertension. The danger of transtentorial or tonsillar herniation is minimized by considering lumbar drainage in the presence of discernible basilar cisterns only.

Continuous lumbar drainage for the preoperative management of patients with aneurysmal subarachnoid hemorrhage.

Continuous drainage of lumbar cerebrospinal fluid (CSF) was analyzed for the preoperative management of patients with aneurysmal subarachnoid hemorrhage (SAH) in 50 consecutive cases of surgically treated aneurysmal SAH. Patients were divided into a lumbar drainage group, in whom continuous lumbar CSF drainage was established for preoperative management, and a non-lumbar drainage group. Rebleeding from the aneurysm during the insertion of the lumbar drainage tube and during continuous lumbar drainage, effect on the control of the systolic blood pressure, and effect on the sedation of the patient were examined. Continuous lumbar CSF drainage significantly decreased the systolic blood pressure. Seven of 17 patients in the non-lumbar drainage group had systolic blood pressure uncontrollable to below 150 mmHg even when a large amount of nicardipine was used, whereas only two of 33 patients had the same problem in the lumbar drainage group. Sedation was better in the patients in the lumbar drainage group with a smaller amount of analgesics. The rebleeding rate was 11.7% among patients in the non-lumbar drainage group, and 9.09% among patients in the lumbar drainage group. No rebleeding occurred during insertion of the lumbar drainage catheter. Continuous lumbar CSF drainage improved control of systolic pressure and sedation, and is a useful method of preoperative management for patients with aneurysmal SAH.

Persistent posttraumatic cerebrospinal fluid leakage

Persistent posttraumatic cerebrospinal fluid (CSF) leakage frequently complicates skull base fractures. Although many CSF leaks will cease without treatment, patients with CSF leaks that persist greater than 24 hours may be at increased risk for meningitis, and many will require surgical intervention. The authors reviewed their 15-year experience with posttraumatic CSF leaks that persisted longer than 24 hours. The authors reviewed the medical records of 51 patients treated between 1984 and 1998 with CSF leaks that persisted for 24 hours or longer after traumatic head injury. In 27 patients (55%) spontaneous resolution of CSF leakage occurred at an average of 5 days posttrauma. In 23 patients (45%) surgery was required to resolve the leakage. Eight patients (16%) with occult CSF leaks presented with recurrent meningitis at an average of 6.5 years posttrauma. Forty-three (84%) patients with CSF leaks sustained a skull fracture, most commonly involving the frontal sinus, whereas parenchymal brain injury or extraaxial hematoma was demonstrated in only 18 patients (35%). Delayed CSF leaks, with an average onset of 13 days posttrauma, were observed in eight patients (16%). Among patients with clinically evident CSF leakage, the frequency of meningitis was 10% with antibiotic prophylaxis, and 21% without antibiotic prophylaxis. Thus, prophylactic antibiotic administration halved the risk of meningitis. A variety of surgical approaches was used, and no significant neurological morbidity occurred. Three (13%) of 23 surgically treated patients required additional surgery to treat continued CSF leakage. A significant proportion of patients with CSF leaks that persist greater than 24 hours will require surgical intervention. Prophylactic antibiotic therapy may be effective in this group of patients. Patients with skull base or frontal sinus fractures should be followed to detect the occurrence of delayed leakage. Surgery-related outcome is excellent.

The “presyrinx” state: is there a reversible myelopathic condition that may precede syringomyelia?

Alteration of cerebrospinal fluid (CSF) flow has been proposed as an important mechanism leading to the development of syringomyelia. We hypothesize that a "presyrinx" condition due to potentially reversible alteration in normal CSF flow exists and that its appearance may be due to variations in the competence of the central canal of the spinal cord. Five patients with clinical evidence of myelopathy, no history of spinal cord trauma, enlargement of the cervical spinal cord with T1 and T2 prolongation but no cavitation, evidence for altered or obstructed CSF flow, and no evidence of intramedullary tumor or a spinal vascular event underwent MR imaging before and after intervention that alleviated obstruction to CSF flow. Preoperatively, all patients demonstrated enlarged spinal cords and parenchymal T1 and T2 prolongation without cavitation. Results of magnetic resonance (MR) imaging examinations following intervention in all patients showed resolution of cord enlargement and normalization or improvement of cord signal abnormalities. In one patient with severe arachnoid adhesions who initially improved following decompression, late evolution into syringomyelia occurred in association with continued CSF obstruction. Nontraumatic obstruction of the CSF pathways in the spine may result in spinal cord parenchymal T2 prolongation that is reversible following restoration of patency of CSF pathways. We refer to this MR appearance as the "presyrinx" state and stress the importance of timely intervention to limit progression to syringomyelia.

Influence of segmental spinal cord perfusion on intrathecal oxygen tension during experimental thoracic aortic crossclamping

Purpose: The purpose of this study was to evaluate the possibility of identifying alterations in blood supply to the spinal cord during thoracic aortic crossclamping. Methods: In 17 pigs, a multiparameter PO 2, PCO 2, and pH sensor was introduced into the intrathecal space for continuous monitoring of cerebrospinal fluid (CSF) oxygenation during aortic crossclamping. An epidural laser Doppler probe was used to measure spinal cord flux. After insertion of an aortic shunt from the left subclavian to the left iliac artery and interruption of the right subclavian and lumbar arteries (L2-L5), the thoracic aorta just distal to the left subclavian artery was clamped for 60 minutes. By placement of the distal aortic crossclamping below the level of L1 in group A (n = 9 animals), perfusion of only the abdominal visceral arteries was maintained. In group B (n = 8 animals), the distal aortic crossclamping was above the level of T12, and thus some spinal cord perfusion was maintained through the aortic shunt. Results: The significant decrease in CSF PO 2 was observed within 3 minutes after the placement of the proximal aortic crossclamping and was normalized in all animals after establishment of the shunt flow. In group A, distal aortic crossclamping caused a decrease in CSF PO 2 with at least 50% of the preclamping values within 3 minutes. The mean CSF PO 2 of 2.99 ± 0.70 kPa at 60 minutes of distal aortic crossclamping in group B was significantly higher than in group A (0.11 ± 0.11 kPa; P < .001). In group A, PCO 2 measurements showed no significant changes in 3 minutes after distal aortic crossclamping but revealed significantly higher values at 30 and 60 minutes compared with group B. Spinal cord flux values showed similar changes as CSF PO 2 during the whole experiment in both groups. Conclusion: In this experimental model of aortic crossclamping, continuous CSF oxygen tension monitoring allows rapid detection of alterations in spinal cord circulation. (J Vasc Surg 2000;31:164-70.)

The effect of lumbar puncture stress on dopamine and serotonin metabolites in human cerebrospinal fluid

In order to examine concentrations of cerebrospinal fluid (CSF) neurochemicals, the technique of lumbar puncture is typically used. However, the effect of the intrinsic stress of undergoing a lumbar puncture on CSF monoamine concentrations in humans has not yet been established. We used lumbar puncture followed 3 h later by continuous CSF sampling to examine the effect of lumbar puncture on levels of the dopamine and serotonin metabolites homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), respectively. Additionally, we examined the effect of lumbar puncture on the CSF HVA to 5-HIAA ratio. Immediately post lumbar puncture, CSF concentrations of HVA and 5-HIAA were, respectively, only 51 and 54% of the mean levels detected hours later. However, the HVA to 5-HIAA ratio remained stable during lumbar puncture. While HVA and 5-HIAA levels in CSF obtained via lumbar puncture reflect highly variable responses to the stress of the procedure, the ratio of these metabolites is unaffected.

The relationship between evoked potentials and measurements of S-100 protein in cerebrospinal fluid during and after thoracoabdominal aortic aneurysm surgery

Objective: This study was performed to correlate the changes in concentration of S-100 protein in the cerebrospinal fluid (CSF) during and after thoracoabdominal aortic aneurysm (TAAA) surgery with the results of somatosensory and motor evoked potential monitoring. Methods: The study was designed as a prospective study at St Antonius Hospital in Nieuwegein, The Netherlands. The participants were 19 patients who were undergoing elective TAAA surgery. CSF samples for analysis of S-100 protein were drawn after the induction of anesthesia, during the cross-clamp period of the critical aortic segment, after 5 minutes of reperfusion of this segment, during the closure of the skin, and 24 hours after the closure of the skin. In all the patients, continuous intraoperative recording of myogenic motor potentials evoked by transcranial electrical stimulation (tcMEP) and somatosensory potentials evoked by stimulation of the posterior tibial nerve took place to monitor the integrity of the spinal cord. The operative technique consisted of staged or sequential clamping to maximize the beneficial effect of the distal perfusion by the left heart bypass, continuous CSF drainage to keep the CSF pressure below 10 mm Hg, and moderate hypothermia (32°C rectal temperature). We correlated the measured concentrations of S-100 protein in CSF with the results of evoked potential monitoring during surgery and the number of intercostals reimplanted and oversewn. Results: In all the patients, the concentration of S-100 protein was increased in CSF. The highest concentration of S-100 protein was found in the CSF sample taken 5 minutes after reperfusion of the critical aortic segment. There was a good (negative) correlation between the changes in S-100 protein in CSF and the changes in motor evoked potential monitoring during the cross-clamp period. The best (negative) correlation was detected between the S-100 protein elevation in the CSF sample drawn 5 minutes after reperfusion and the tcMEP amplitude reduction during clamping (r = –0.73; P = .007). No relation was found between the S-100 protein dynamics in CSF and somatosensory evoked potential monitoring. A positive (r = 0.58; P = .05) correlation was found between the change in tcMEP amplitude during clamping and the number of reattached intercostals. A moderate to good (r = –0.5 to –0.7; P < .05) correlation between the number of reattached intercostals and the changes in S-100 protein concentration in CSF during TAAA surgery was found. Our data show that transient elevations in S-100 protein after cross clamping are larger in those patients with marked decrease in tcMEP from baseline during the cross-clamp period. Conclusion: A correlation is shown between an increasing concentration of S-100 protein in CSF and a reduction in tcMEP amplitude during cross clamping of the aorta. The S-100 protein in CSF seems to be a marker of potential clinical value in the evaluation of the effects of procedures to detect and reduce spinal cord ischemia. (J Vasc Surg 1999;30:293-300.)

Thoracoabdominal Aortic Surgery With Special Reference to Spinal Cord Protection and Perfusion Techniques

Introduction show reduced spinal cord perfusion following crossclamping of the descending thoracic aorta or the Despite many protective measures during and after azygos vein. Drainage of spinal fluid during crosssurgery, the morbidity and mortality of thoraclamping increases microcirculatory perfusion of the coabdominal aortic aneurysm (TAAA) repair remains spinal cord. These experimental results were clinically a major concern. Spinal cord ischaemia and renal confirmed by combining cerebrospinal fluid drainage failure are the main complications besides myocardial and distal aortic perfusion, significantly reducing infarction, multiple organ failure, visceral ischaemia neurologic complications after repair of TAAA types and pulmonary problems. The first Nordic workshop I and II. Thus, CSF drainage is now regarded as an of TAAAs was organised in 1992 and it was then important adjunct. There was no dissent from the generally agreed that the surgical method of choice was requirement for continuous CSF drainage to maintain the Crawford technique with direct cross-clamping. a pressure of less than 10 mmHg. There was agreement During the last 5 years, however, different techniques that a CSF pressure exceeding 30 mmHg was ashave been developed and the aim of the second worksociated with paraplegia. Nevertheless, it was reshop was to evaluate progress in experimental and cognised that CSF drainage alone does not prevent all clinical research and to discuss the potential benefits ischaemic events of the spinal cord. for the patient. Although a short clamp time is of importance the majority of participants were against the rapid no heparin “clamp and go” method, in favour of distal aortic perfusion, low dose heparin (1 mg/kg) and careSpinal Cord Ischaemia and Protection ful intercostal artery incorporation. Local cooling of the spinal cord or systemically by extracorporeal cirIn the workshop it was confirmed that the most exculation was seen to increase the ischaemic tolerance. tensive aneurysm (type II) carries the highest risk of Participants felt that detection of spinal cord ischparaplegia and mortality. Spinal cord injury is largely aemia during surgery would be a great advantage so due to the duration of ischaemia and failure to rethat measures to re-establish blood supply to the spinal establish blood flow after aortic repair. The mechanism cord could be improved. It was generally agreed that of delayed paraplegia is not completely understood somatosensory evoked potentials (SSEP) are inaccurate but is associated with raised cerebrospinal fluid (CSF) because they do not reflect motor function. Several pressure, intraand postoperative hypotensive periods techniques for monitoring motor neuron pathways or occluded reattached intercostal arteries. exist, but only myogenic responses are entirely specific To combat spinal cord ischaemia, the importance of for the status of the motor neurons in the anterior the intercostal blood supply from T6 to L1 was stressed. horn. Transcranial motor-evoked potentials (MEP) Animal models and the use of laser Doppler fluxmetry were used in one centre and were demonstrated to be important in monitoring spinal cord function. Spinal ∗ Please address all correspondence to: M. J. H. M. Jacobs, Academic cord ischaemia could be detected within minutes and Medical Center, Department of Vascular Surgery, P/O box 22700, 1100 De Amsterdam, The Netherlands. the technique helped to identify segmental arteries

Continuous covariability of dopamine and serotonin metabolites in human cerebrospinal fluid

Background: Experiments in lower animals and humans have demonstrated the existence of functional interactions between serotonin and dopamine in neuronal tissue. However, the relationship between parameters of serotonin and dopamine neuronal activity over time within the central nervous system (CNS) of the individual human has not yet been established. Methods: We used continuous cerebrospinal fluid (CSF) sampling over 6 hours to test the hypothesis that the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and the dopamine metabolite homovanillic acid (HVA) significantly covary in concentration over time. Two groups of normal volunteers (total n = 16) were studied at separate hospitals and CSF was assayed for 5-HIAA and HVA by high-performance liquid chromatography (HPLC). Three subjects underwent repeat CSF-withdrawal procedures after a 6-week interval. Results: Strong and sustained positive covariability in concentrations of HVA and 5-HIAA was observed in the CSF of individual humans. High intraindividual correlation coefficients were routinely observed; the mean intraindividual correlation coefficients were +0.897 and +0.871 in the two normal volunteer groups. The HVA to 5-HIAA concentration ratio in CSF was 2.2 ± 0.7 with very little variability over intervals ranging from minutes to weeks. Conclusions: The balance between CSF dopamine and serotonin metabolite concentrations remains relatively constant over time in healthy humans. Serial measures of CSF dopamine and serotonin metabolites within the same person could be an effective model in which to explore the interrelationships between these systems in various psychiatric syndromes, in response to drug treatment, and during provocative testing.

Tryptophan depletion during continuous CSF sampling in healthy human subjects.

The tryptophan (TRP) depletion paradigm has been employed to investigate mood and behavioral effects of acutely lowering plasma TRP, and presumably brain serotonin (5-hydroxytryptamine [5-HT]) levels through administration of a special diet and/or amino acid drink. Our goal was to test the assumption that a corresponding fall in central levels of TRP and 5-HT (measured by its major metabolite, 5-hydroxyindoleacetic acid [5-HIAA]) occurs during the standard execution of this method in healthy adult subjects. Three males and two females completed the protocol, which included a one-day low-TRP diet and a TRP-free amino acid drink. Lumbar puncture was performed, with placement of an indwelling catheter connected to a peristaltic pump and fraction collector. Cerebrospinal fluid (CSF) was sampled continuously for a 13.5-hour period (before, during, and after the drink), with fractions removed every 15 minutes. Plasma samples were simultaneously obtained. CSF TRP levels and plasma TRP levels were highly correlated, falling a mean of 92% and 85% from baseline, respectively. CSF nadirs were reached several hours after plasma nadirs. CSF 5-HIAA decreased modestly (24% to 40%, mean 31% change from baseline), with lowest concentrations observed 8-12 hours after the amino acid drink. These data suggest that TRP depletion results in substantial declines in central 5-HT turnover.

Cerebrospinal fluid neuroendocrinology of alcohol misusers.

Cerebrospinal fluid (CSF) neurohumors reflect central nervous system physiology in a way that peripheral indices can not. We reviewed clinical studies of CSF biogenic amines and neurohormones in alcohol misusers during various stages of withdrawal or abstinence and found them difficult to compare because of highly variable experimental methods, reliance on single time collections (lumbar punctures) that fail to control for potential stress-induced effects of the procedure, lack of control for tobacco use, and a paucity of non-alcoholmisusing controls. However, taken together, the data thus far show that a variety of neuroactive substances are reduced in concentration in the CSF of some alcohol misusers. Low CSF levels of corticotropinreleasing hormone, beta-endorphin, norepinephrine, diazepam-binding inhibitor, 5-hydroxyindoleacetic acid and somatostatin have all been reported. Whether the decreased CSF levels of these neurohormones and neurotransmitters are a cause or consequence of alcoholism has not been determined. In fact, further studies using serial or continuous CSF sampling techniques with homogeneous, better-characterized patients and normal volunteers are still needed to establish the precise CSF neurochemical abnormalities in alcohol misusers.