Cranioplasty with autologous cryopreserved bone after decompressive craniectomy: complications and risk factors for developing surgical site infection.

BACKGROUND: Renewed interest has developed in decompressive craniectomy, and improved survival is shown when this treatment is used after malignant middle cerebral artery infarction. The aim of this study was to investigate the frequency and possible risk factors for developing surgical site infection (SSI) after delayed cranioplasty using autologous, cryopreserved bone. METHODS: This retrospective study included 74 consecutive patients treated with decompressive craniectomy during the time period May 1998 to October 2010 for various non-traumatic conditions causing increased intracranial pressure due to brain swelling. Complications were registered and patient data was analyzed in a search for predictive factors. RESULTS: Fifty out of the 74 patients (67.6 %) survived and underwent delayed cranioplasty. Of these, 47 were eligible for analysis. Six patients (12.8 %) developed SSI following the replacement of autologous cryopreserved bone, whereas bone resorption occurred in two patients (4.3 %). No factors predicted a statistically significant rate of SSI, however, prolonged procedural time and cardiovascular comorbidity tended to increase the risk of SSI. CONCLUSIONS: SSI and bone flap resorption are the most frequent complications associated with the reimplantation of autologous cryopreserved bone after decompressive craniectomy. Prolonged procedural time and cardiovascular comorbidity tend to increase the risk of SSI.

Sevoflurane and propofol depolarize mitochondria in rat and human cerebrocortical synaptosomes by different mechanisms.

BACKGROUND AND OBJECTIVES: The mitochondrial membrane potential drives the main functions of the mitochondria. Sevoflurane depolarizes neural mitochondria. There is still, however, limited information concerning the effect of anaesthetics on neural mitochondria in humans. The effect of sevoflurane and propofol on the intracellular Ca(2+) concentration [Ca(2+)](i) and the mitochondrial membrane potential (DeltaPsi(m)) was therefore compared in rat and human synaptosomes, and the changes were related to interventions in the electron transport chain. METHODS: Synaptosomes from rat and human cerebral cortex were loaded with the fluorescent probes fura-2 ([Ca(2+)](i)) and JC-1 (DeltaPsi(m)) before exposure to sevoflurane 1 and 2 minimum alveolar concentration (MAC), and propofol 30 and 100 microM. The effect on the electron transport chain was investigated by blocking complex V. RESULTS: Sevoflurane and propofol decreased DeltaPsi(m) in rat synaptosomes in a dose-dependent manner, and to the same extent by equipotent doses. Inhibition of complex V enhanced the depolarizing effect of sevoflurane 2 MAC, but not of propofol 100 microM. Neither sevoflurane nor propofol affected [Ca(2+)](i) significantly. Sevoflurane and propofol decreased DeltaPsi(m) in human synaptosomes to the same extent as in the rat experiments. CONCLUSIONS: Sevoflurane and propofol at equipotent doses depolarize the mitochondria in rat and human nerve terminals to the same extent. The depolarizing effect of propofol on Psi(m) was more rapid in onset than that of sevoflurane. Whereas sevoflurane inhibits the respiratory chain sufficiently to cause ATP synthase reversal, the depolarizing effect of propofol seems to be related to inhibition of the respiratory chain from complex I to V.

Isoflurane-induced depolarization of neural mitochondria increases with age.

BACKGROUND AND OBJECTIVES: The mitochondrial membrane potential (DeltaPsi(m)) drives the three fundamental functions of mitochondria, namely adenosine triphosphate (ATP) generation, Ca(2+) uptake/storage, and generation/detoxification of ROS. Isoflurane depolarizes neural mitochondria. The sensitivity for general anesthetics increases with age, but the mechanism for this age-related sensitivity is still unknown. We compared the effect of isoflurane on [Ca(2+)](i) and DeltaPsi(m) in isolated pre-synaptic terminals (synaptosomes) from neonatal, adolescent, and adult rats and the influence of interventions in the respiratory chain was assessed. METHODS: Synaptosomes were loaded with the fluorescent probes fura-2 ([Ca(2+)](i)) and JC-1 (DeltaPsi(m)) and exposed to isoflurane 1 and 2 minimum alveolar concentration (MAC). The effect on the electron transport chain was investigated by blocking complexes I and V. RESULTS: In neonatal rats isoflurane had no significant effect on DeltaPsi(m). In adolescent and adult synaptosomes, however, isoflurane 1 and 2 MAC decreased DeltaPsi(m). Isoflurane 2 MAC increased [Ca(2+)](i) in neonatal and adolescent rats, but not in adult synaptosomes. In Ca(2+)-depleted medium, isoflurane still decreased DeltaPsi(m), while [Ca(2+)](i) remained unaltered. By blocking complex V of the respiratory chain, the isoflurane-induced mitochondrial depolarization was enhanced in all age groups. Blocking complex I depolarized the mitochondria to the same extent as isoflurane 2 MAC, but without any additive effect. CONCLUSIONS: The depolarizing effect of isoflurane on neural mitochondria is more pronounced in the adolescent and adult than in neonatal synaptosomes. The increased mitochondrial sensitivity with age seems to be related to the reversed function of the ATP synthase of the electron transport chain.

Volatile anaesthetics depolarize neural mitochondria by inhibiton of the electron transport chain.

BACKGROUND: The mitochondrial membrane potential (DeltaPsim) controls the generation of adenosine triphosphate (ATP) and reactive oxygen species, and sequesteration of intracellular Ca2+[Ca2+]i. Clinical concentrations of sevoflurane affect the DeltaPsim in neural mitochondria, but the mechanisms remain elusive. The aim of the present study was to compare the effect of isoflurane and sevoflurane on DeltaPsim in rat pre-synaptic terminals (synaptosomes), and to investigate whether these agents affect DeltaPsim by inhibiting the respiratory chain. METHODS: Synaptosomes were loaded with the fluorescent probes JC-1 (DeltaPsim) and Fura-2 ([Ca2+]i) and exposed to isoflurane or sevoflurane. The effect of the anaesthetics on the electron transport chain was investigated by blocking complex I and complex V. RESULTS: Isoflurane 1 and 2 minimum alveolar concentration (MAC) decreased the normalized JC-1 ratio from 0.92 +/- 0.03 in control to 0.86 +/- 0.02 and 0.81 +/- 0.01, respectively, reflecting a depolarization of the mitochondrial membrane (n = 9). Isoflurane 2 MAC increased [Ca2+]i. In Ca2+-depleted medium, isoflurane still decreased DeltaPsim while [Ca2+]i remained unaltered. The effect of isoflurane was more pronounced than for sevoflurane. Blocking complex V of the respiratory chain enhanced the isoflurane- and sevoflurane-induced mitochondrial depolarization, whereas blocking complex I and V decreased DeltaPsim to the same extent in control, isoflurane and sevoflurane experiments. CONCLUSIONS: Isoflurane and sevoflurane may act as metabolic inhibitors by depolarizing pre-synaptic mitochondria through inhibition of the electron transport chain, although isoflurane seems to inhibit mitochondrial function more significantly than sevoflurane. Both agents inhibit the respiratory chain sufficiently to cause ATP synthase reversal.

Sevoflurane depolarizes pre-synaptic mitochondria in the central nervous system.

BACKGROUND: Volatile anaesthetics protect the heart from ischaemic injury by activating mitochondrial signalling pathways. The aim of this study was to test whether sevoflurane, which is increasingly used in neuroanaesthesia, affects mitochondrial function in the central nervous system by altering the mitochondrial membrane potential (DeltaPsi(m)). METHODS: In order to correlate free cytosolic Ca(2+) ([Ca(2+)](i)) and DeltaPsi(m), rat neural presynaptic terminals (synaptosomes) were loaded with the fluorescent probes fura-2 and JC-1. During sevoflurane exposure, 4-aminopyridine (4-AP) 500 micro M to induce pre-synaptic membrane depolarization or carbonylcyanide-p-(trifluoromethoxy)-phenylhydrazone (FCCP) 1 micro M to induce maximum mitochondrial depolarization was added. In order to block mitochondrial ATP-regulated K(+)-channels (mitoK(ATP)), the antagonist 5-hydroxydecanoate (5-HD) 500 micro M was added. RESULTS: In Ca(2+)-containing medium, both sevoflurane 1 and 2 MAC gradually decreased the normalized JC-1 ratio from 0.96 +/- 0.01 in control to 0.92 +/- 0.01 and 0.89 +/- 0.01, representing a depolarization of DeltaPsi(m) (n = 9, P < 0.05). Sevoflurane 2 MAC increased [Ca(2+)](i). In Ca(2+)-depleted medium, sevoflurane 1 and 2 MAC depolarized DeltaPsi(m), while [Ca(2+)](i) remained unaltered. Sevoflurane 2 MAC attenuated the 4-AP-induced depolarization of DeltaPsi(m). When mitoK(ATP) was blocked, the sevoflurane-induced depolarization of DeltaPsi(m) was attenuated, but not blocked. The depolarizing effect of sevoflurane on DeltaPsi(m) compared with FCCP was calculated to 13.2 +/- 1.3% in Ca(2+)-containing and 15.1 +/- 1.2% in Ca(2+)-depleted medium (n = 7). CONCLUSIONS: Sevoflurane depolarizes DeltaPsi(m) in rat synaptosomes, and the effect is not dependent on Ca(2+)-influx to the cytosol. Opening of mitoK(ATP) is partly responsible for the depolarizing effect of sevoflurane.

MR imaging of ventriculus terminalis of the conus medullaris. A report of two operated patients and a review of the literature.

We report on 2 patients in whom a cystic dilation of the conus medullaris was incidentally found at MR imaging carried out in the work-up for sciatica. The cysts were well circumscribed and had signal intensity identical to the CSF on both T1- and T2-weighted images. There was no evidence of contrast enhancement. None of the patients had specific symptoms related to the spinal cord. At surgery, no evidence of malignancy was seen in any of the patients. A benign cystic dilation, also called dilated ventriculus terminalis, occasionally can be seen in the conus medullaris as an incidental finding at thoracolumbar MR imaging. Unless the expansion per se indicates cyst drainage, these patients may be monitored by clinical and MR follow-up, avoiding surgery in a substantial number of cases.

The in vitro effects of crystalloids and colloids on coagulation.

Classically haemodilution is regarded as causing coagulopathy. However, haemodilution with saline seems to cause a hypercoagulable state both in vivo and in vitro. The aim of the present study was to measure the effect of mild to severe haemodilution using thrombelastography. Blood samples were taken in 12 healthy volunteers and divided into seven aliquots. One aliquot was undiluted and acted as control. The other six were diluted with normal saline, Ringer Acetate, 4% albumin, Dextran 70, 6% and 10% hydroxyethylstarch to 10%, 20%, 40%, 50% and 60% dilution. The dilution was checked by measuring the haemoglobin concentration. Each aliquot was placed in a temperature-controlled thrombelastography channel. Increased coagulation activity, as measured by thrombelastography changes, was detected at low and medium levels of dilution with all the tested solutions. At more than 40% dilution, coagulation returned to normal while in the case of dextran and hydroxyethylstarch coagulopathy developed. For crystalloids and albumin,dilution had to exceed 50% before coagulation was impaired. If these findings can be reproduced in vivo, they may have implications for transfusion practice and prophylaxis against thrombosis.

The effect of sevoflurane on glutamate release and uptake in rat cerebrocortical presynaptic terminals.

BACKGROUND: Volatile anaesthetics exert their effect in the brain mainly by reducing synaptic excitability. Isoflurane abates excitation by reducing the release and increasing the uptake of transmitter glutamate into the presynaptic terminal. The exact molecular mechanisms exerting these effects, however, are not clear. Voltage-gated calcium channels have been proposed as the pharmacological target. The present study examines the effect of sevoflurane on synaptic glutamate release and free cytosolic calcium and the effect on high- and low-affinity uptake of L-glutamate using isolated presynaptic terminals prepared from rat cerebral cortex. METHODS: Released glutamate was measured fluorometrically in a spectrophotometer as the fluorescence of NADPH and calcium as the fluorescence of fura-2. 4-aminopyridine was used to induce membrane depolarization. Glutamate uptake was measured in a series of different concentrations of L-glutamate corresponding to the high- and the low- affinity uptake systems adding a fixed concentration og radiolabelled glutamate. The labelling was measured by counting disintegrations per min in a beta-scintillation counter. RESULTS: Sevoflurane reduced the calcium-dependent glutamate release in a dose-dependent manner as sevoflurane 1.5, 2.5 and 4.0% reduced the release by 58, 69 and 94%, respectively (P<0.05). Membrane depolarization induced an increase in free cytosolic calcium by 25%. Sevoflurane did not affect this increase. Neither the high- nor the low-affinity uptake transporter systems are affected by the anaesthetic. CONCLUSION: These results indicate that different volatile anaesthetics may act differently on the presynaptic terminal. The exact modes of action have to be further investigated.

Measured increase in intracellular Ca(2+) during stimulated release of endogenous glutamate from human cerebrocortical synaptosomes.

Presynaptic terminals (synaptosomes) prepared from guinea pig and rat cerebral cortex release endogenous glutamate in a Ca(2+)-dependent manner in response to membrane depolarisation. In the present study, synaptosomes were prepared from human cerebral cortex removed in association with temporal lobe resections in epileptic patients. The cytosolic free Ca(2+) concentration increased from 474+/-66 before to 649+/-89 nM after 2 min depolarisation. The basal level of free cytosolic Ca(2+) is higher and the increase in response to depolarisation is more pronounced in human synaptosomes than observed in animal experiments. The Ca(2+)-dependent glutamate release, estimated as the difference between total - and the Ca(2+)-independent glutamate release, increased from 0 to 5.4+/-1.9 nmol/mg protein. The released amount of glutamate is larger than reported in animal models. These results demonstrate that membrane depolarisation of synaptosomes from human brain evokes a rapid rise in cytosolic free Ca(2+) and a more prolonged rise in synaptic, Ca(2+)-dependent glutamate release.

[Early postoperative complications in carotid surgery]. / Tidlige postoperative komplikasjoner ved carotiskirurgi.

Carotid endarterectomy has a documented stroke preventing effect in symptomatic high-grade carotid stenosis when the rate of serious complications is below 6%. In the period 1986-96, 160 procedures were performed on 150 patients at the Department of Neurosurgery, Ullevål Hospital. Oslo. The indication for surgery was hemispheric transient ischemic attack and/or amaurosis fugax in 137 patients and/or minor stroke in 49 in addition to a high-grade stenosis. Mean age was 61 years (42-74 years). One patient (0.6%) died four hours after surgery. Three patients (1.9%) suffered disabling postoperative stroke. The rate of serious complications was thus 2.5%. In addition, nine patients experienced minor and temporary paresis. Three patients were reoperated for haematoma and one for wound infection. Our surgical morbidity and mortality rate is comparable to larger series.

[Continuous intrathecal infusion of baclofen. A new therapeutic method for spasticity]. / Kontinuerlig intratekal infusjon med baklofen. Ny behandlingsmetode for spastisitet.

Intrathecal administration of baclofen is now generally accepted as a powerful treatment of spasticity caused by spinal lesions. 35 patients with severe spasticity, 29 of spinal origin and six of supraspinal origin resistant to conservative treatment, had a programmable pump (Synchromed, Medtronic) for continuous intrathecal baclofen infusion implanted. The patients were followed-up for an average of 29 months (0-68). The initial effect of the treatment was positive for all patients; spasms were less frequent, there was remission of pain caused by cramps, and in some cases improved ambulation. In five patients, however, the pump was later removed: in two patients the pump ceased to be effective, two patients became infected, and one experienced multiple catheter problems. Problems with the catheter was the most common complication experienced, and this was seen in nine patients. Three patients died of the underlying disease. The majority of patients became accommodated to intrathecal baclofen and it was necessary to administer increasingly larger doses to maintain the clinical effect. Long-term control of spinal spasticity by intrathecal baclofen can be achieved in most patients, but close follow-up is necessary for assessing efficacy and refilling the pump.

Effect of isoflurane on release and uptake of gamma-aminobutyric acid from rat cortical synaptosomes.

We have studied the effect of isoflurane on potassium-evoked release and high-affinity uptake of gamma-aminobutyric acid (GABA) in rat cortical synaptosomes. Isoflurane 1.5% and 3% increased calcium-dependent release by 38% and 36% of control values, respectively (P < 0.05). Calcium-independent release was reduced correspondingly by 24% and 26% (P < 0.05). High-affinity uptake of GABA was not affected by isoflurane. The findings of increased synaptic GABA release combined with unaltered uptake suggest that isoflurane increases GABA in the synaptic cleft and thus may enhance inhibition.

The effect of isoflurane on brain amino acid release and tissue content induced by energy deprivation.

This article describes the effect of isoflurane on amino acid release and tissue content induced by energy deprivation in slices of rat hippocampus. Energy deprivation (95% N2 / 5% CO2 and glucose free medium) (ED) induced an increase in the release of all amino acids measured, with the exception of glutamine. The tissue content of all amino acids except gamma-aminobutyric acid (GABA) and arginine was concomitantly reduced. Isoflurane (1.5% and 3.0%) reduced glutamate release during ED by 27% and 28% (p < 0.05 as compared with release without isoflurane), respectively, whereas the tissue content was slightly increased. Similarly, GABA release was reduced by 25% and 25% (p < 0.05 as compared with release without isoflurane) accompanied by an insignificant enhancement in tissue content as compared with ED without isoflurane. Isoflurane reduced the release of taurine and most of the other amino acids. The total amount of all amino acids (both released and retained) was not significantly altered by the anesthetic. These observations demonstrate that isoflurane can modify the changes in amino acid handling induced by energy deprivation.

Isoflurane reduces synaptic glutamate release without changing cytosolic free calcium in isolated nerve terminals.

The molecular mechanism of volatile anaesthetic action on presynaptic glutamate release is not clear. An inhibitory effect on voltage-gated calcium channels has been proposed. The present study examines the effect of isoflurane on cytosolic free calcium and synaptic glutamate release from isolated nerve terminals. Synaptosomes from rat cerebral cortex were used. Glutamate was measured with a continuous fluorometric measurement in a spectrophotometer as the fluorescence of NADPH and calcium as the fluorescence of fura-2. Isoflurane reduced the calcium-dependent glutamate release evoked by membrane depolarization with 4-aminopyridine in an inversely dose-dependent manner. The glutamate release was reduced by 56, 43 and 36% in response to isoflurane 0.5, 1.5 and 3.0%, respectively (for all: P < 0.05). Membrane depolarization evoked a rise in cytosolic free calcium of approximately 34%. Addition of isoflurane (0.5, 1.5 and 3.0%) produced no significant change in cytosolic free calcium. These results indicate that the isoflurane-induced reduction in presynaptic glutamate release is caused by other mechanisms than blocking voltage-gated calcium channels. As the release is inversely dose-dependent, two or more mechanisms could be involved.

Chloride influx during cerebral energy deprivation.

The purpose of the present study was to investigate the possible role of chloride influx and GABA release during cerebral energy deprivation (ED). The functional activity measured by evoked activity (population spike) in hippocampal slices was recorded during nine minutes of ED and 60 minutes recovery. Treatment groups were exposed to ED following administration of the GABAA antagonist penicillin G (pc G) or substitution of extracellular chloride. The release of glutamate and GABA was measured by HPLC. The efflux of 36Cl from preloaded slices was measured during ED with and without blocking the GABAA receptor. The population spike disappeared during ED, and there was a marked release of GABA and glutamate. During recovery the population spike recovered partially. Both application of pc G and substitution of extracellular chloride during ED improved population spike recovery. Uptake of radiolabeled chloride was significantly reduced by pc G. Glutamate release, but not GABA, was significantly reduced by chloride substitution. These results indicate a possible role of chloride mediated injury during ED, and suggest that chloride entry may partly occur through ligand-operated channels. Furthermore there may be an early chloride dependent release of glutamate during cerebral ischemia, whereas later release seems to be chloride independent.

[Intraspinal hematoma after thoracic epidural analgesia]. / Intraspinal bløning etter torakal epidural smertebehandling.

In one year three patients were operated on for spinal haematomas following thoracic epidural analgesia. All three patients experienced back pain and developed progressive paraparesis, one in connection with insertion of the catheter and two after its removal. A spinal block was visualized using MRI in two patients and myelography in one. The patients were operated on with posterior decompression. In two patients an epidural haematoma was evacuated. Both patients recovered neurologic function, one completely. The third patient, who had a subarachnoidal hemorrhage and an intramedullar haematoma, remained paralytic.

Survival, prognostic factors, and therapeutic efficacy in low-grade glioma: a retrospective study in 379 patients.

PURPOSE: We report survival, prognostic factors, and treatment efficacy in low-grade glioma. PATIENTS AND METHODS: A total of 379 patients with histologic intracranial low-grade glioma received post-operative radiotherapy (n = 361) and intraarterial carmustine (BCNU) chemotherapy (n = 153). Overall survival and prognostic factors were evaluated with the SPSS statistical program (SPSS Inc, Chicago, IL). RESULTS: Median survival (all patients) was 100 months (95% confidence interval [CI], B7 to 113); in age group 0 to 19 years (n = 41), 226 months; in age group 20 to 49 years (n = 263), 106 months; in age group 50 to 59 years (n = 49), 76 months; and for older patients (n = 26), 39 months. Projected survival at 10 and 15 years was 42% and 29%, respectively. Patient age, World Health Organization (WHO) performance status, tumor computed tomography (CT) contrast enhancement, mental changes, or initial corticosteroid dependency were significant independent prognostic factors (p < .05), while histologic subgroup, focal deficits, presence of seizures, prediagnostic symptom duration, tumor category, and tumor stage were not. Patients aged 20 to 49 years with no independent negative prognostic factors (n = 132) had a median survival time of 139 months versus 41 months in patients with two or more factors (n = 33). Patients who presented with symptoms of expansion (n = 97) survived longer when resected (P < .03); otherwise no survival benefit was associated with initial tumor resection compared with biopsy. Intraarterial chemotherapy and radiation doses more than 55 Gy were not associated with prolonged survival. Among 66 reoperated patients, 45% progressed to high-grade histology within 25 months. CONCLUSION: Prognosis in low-grade glioma following postoperative radiotherapy seems largely determined by the inherent biology of the glioma and patient age at diagnosis.

Isoflurane increases the uptake of glutamate in synaptosomes from rat cerebral cortex.

We have studied the effect of increasing concentrations of isoflurane on high- and low-affinity uptake of L-glutamate using synaptosomes from rat cerebral cortex. In the high-affinity uptake range, 0.5% isoflurane had no effect on uptake velocity, while 1.5% and 3.0% isoflurane caused an increase in mean Vmax to 131 (SEM 54) and 210 (103)% of control, respectively. There was no significant change in the K(m) value. Vmax and K(m) values for low-affinity uptake of L-glutamate were unchanged by 1.5% isoflurane. These results provide evidence for an isoflurane-induced increase in high-affinity uptake of glutamate into presynaptic terminals. This effect may contribute to a reduction of transmitter in the synaptic cleft and thereby decreased excitatory synaptic transmission.