[Subarachnoid pleural fistula and subsequent pneumocephalus as complication of vertebral body replacement of the thoracic spine]. / Pleurospinale Fistel und konsekutiver Pneumatozephalus als Komplikation eines Wirbelkörperersatzes an der Brustwirbelsäule.

A pneumocephalus caused by a subarachnoid pleural fistula following spinal surgery using an anterior approach is a rare complication, especially in vertebral body replacement. We report the case of a 66-year-old male suffering from metastatic prostatic cancer of the thoracic spine who underwent replacement of a vertebral body using a transthoracic approach. A pneumocephalus occurred 4 weeks postoperatively resulting in delirium.

Blood flow velocities in the basal vein after subarachnoid haemorrhage. A prospective study using transcranial duplex sonography.

BACKGROUND: Early recognition of emerging delayed neurological deficits (DND) in patients after subarachnoid haemorrhage (SAH) is not always possible by transcranial Doppler sonography. Aim of this study was to investigate a) whether determination of blood flow velocities in deep cerebral basal veins can predict DND in these patients b) the correlation of venous flow velocity to cerebral blood flow (CBF). METHODS: a) We prospectively investigated the mean flow velocity in the basal vein (VBVR), in the middle cerebral artery (VMCA) and in the extracranial internal carotid artery (VICA) in 66 patients after spontaneous SAH. Examinations were performed daily during the first 10 days, using transcranial duplex sonography. Thirty-seven patients had VMCA exceeding 120 cm/s. They were categorised in three groups: 1: no delayed neurological deficit; II: transient DND; III: permanent DND or death associated with vasospasm. b) In another group of 14 patients, interdiane variations in global cerebral blood flow (CBF) measured by the Kety-Schmidt-method were correlated with variations in VBVR, VMCA, and VICA. FINDINGS: a) In patients without deficit, VBVR was significantly elevated above normal values the first day (p < 0.05), and days 5 and 6 (p < 0.1) after VMCA exceeding 120 cm/s. In group III (permanent deficit), flow velocities in the BVR were significantly below normal on day 5 (p < 0.05) and 9 (p < 0.1). b) The correlation between changes in VBVR to changes in CBF (r = 0.78, p < 0.001) was closer than between changes in VMCA to the changes in CBF (r = 0.54, p < 0.05). INTERPRETATION: In case of elevated VMCA, patients with higher VBVR seem to have a better outcome. Changes in CBF correlate better with VBVR than with arterial flow velocities.

Expression of focal adhesion kinase (p125 FAK) and proline-rich tyrosine kinase 2 (PYK2/CAKb) in cerebral metastases, correlation with VEGF-R-, ecNOS III-labelling and morphometric data.

BACKGROUND: Cerebral metastasis occurs in about 20% of all neurosurgical patients. Cerebral metastases have a typical spherical morphology with a common central necrosis and perifocal oedema. It has been proposed that oedema extension, tumour volumes and infiltrative behaviour are partially mediated by vascular endothelial growth factor (VEGF) and nitric oxide (NO). In several systemic tumour entities NO is suggested as a factor which influences the metastatic potential. VEGF has recently been reported to influence the matrix related migratory activity by interaction with focal adhesion kinase (p125FAK) and proline-rich tyrosine kinase beta (PYK2/CAK beta). Nitric oxide, which is produced in metastases by three different NOS isozymes is capable of antagonizing the binding of FAK to matrix integrins. NO, VEGF and FAK/PYK 2 are therefore considered to be important mediators of the cerebral metastatic incidence, growth, infiltration and oedema extension. The aim of our present study was to investigate the expression of p125FAK and the coexpression with PYK2/CAK beta, VEGF-receptor FLT-1, NOS isozymes NOS I-III, capillary density and the histology in 130 specimens of resected cerebral metastatic tumours. A further analysis was performed to morphometrically evaluate tumour and oedema volumes and to correlate the immunohistochemical data in a subgroup of 40 patients. MATERIALS AND METHODS: Cryosections (N = 130) of metastatic resections were investigated immunohistologically using a 4-step scoring evaluation for the expression of NOS I-III, VEGF-receptor FLT-1, and capillary vessel presence by endothelial Von-Willebrand-Factor (VWF) staining. Tumour and oedema extension was measured in preoperative MRI (N = 40) scans by an image-processing device (Kontron) and the ratios of oedema volumes to total tumour volumes were calculated. The data were analysed statistically (Spearman rank order correlation and Kruskal-Wallis ANOVA) and correlated with the clinical data. RESULTS: FAK immunoexpression was observed in 50% of the specimens (31.2% gradings 2 and 3). We observed a significant coexpression (p = 0.0001) with PYK 2 labelling which occurred frequently in 74% of the specimens (42% gradings 2 and 3). The VEGF receptor FLT-1 could be detected in 70% of them, 24% at higher expression values 2 and 3. The expression of NO synthase was frequently observed. NOS I was detected in 83.6% of the specimens, values 2 and 3 in 40.5%. NOS III, the endothelial isoform, was observed in 39.4% of the specimens (gradings 2 and 3) and inducible NOS II in 29.4% (grading 2 and 3) of them. Coexpressions were statistically significant for FAK and NOS III (Spearman p = 0.008) and FAK and VEGF-R (p = 0.03). The morphometric evaluation resulted in tumour volumes between 2.0 and 83 cm3 (mean 22.5 +/- 19.1 SD) with oedema ratios between 0 and 100% (mean 62.2 +/- 22.5 SD). FAK expression correlated significantly (p = 0.06) with tumour volumes and histology. CONCLUSION: The frequent histotypic occurrence of FAK and PYK2 in metastases could be an important factor in the modulation of metastatic capacity and infiltrative behaviour and might influence the disease course. Judging from its frequent expression PYK2 may generate the more relevant signals. A further aspect is the possible interaction with endothelial NOS III and VEGF receptor, which could be important for the infiltrative behaviour in a latent hypoxic scenery and environment.

Blood flow velocities in middle cerebral artery branches after subarachnoid hemorrhage.

In a prospective study, 55 patients were examined by transcranial duplex sonography (TCCS) after subarachnoid hemorrhage (SAH) to determine whether additional transcranial duplex examination on the middle cerebral artery M2 segments would aid in the examination of the MCA stem segment. The mean blood flow velocities and pulsatility index were correlated to the occurrence of delayed ischemic neurologic deficits (DIND). Out of 47 patients included, 21 did not experience any delayed deficit (group I), 15 did (group II), and in 11 the extent to which vasospasm contributed to a neurologic deficit was unclear (group III). The highest blood flow velocity and the greatest increase of mean blood flow velocity on 1 day were significantly higher in groups II and III both in M1 and in M2. In 10 patients in group II, where the onset day of DIND was known exactly, Doppler data indicating ischemia before or at the time of DIND were observed in nine. In eight patients, Doppler of the MCA stem alone would have provided enough information to recognize the risk of symptomatic vasospasm; in one patient, only the M2 Doppler gave an indication of ischemic complication. Transcranial duplex sonography may provide additional information to TCD by accurate delineation of M1/M2 vasospasm and therefore may help plan cerebral angiography and neurointerventional treatment.

Entry of tromethamine into the cerebrospinal fluid of humans after cerebrovascular events.

OBJECTIVE: The intravenous administration of tromethamine (INN, trometamol) lowers the intracranial pressure in patients with brain edema. One postulated mechanism of action is the increase of the pH of the cerebrospinal fluid. METHODS: To study tromethamine kinetics in serum and cerebrospinal fluid, nine patients with external ventriculostomies and normal serum creatinine values received 60 mmol intravenous tromethamine (Tris 36.34%, pH 11) over 30 minutes. Serum and cerebrospinal fluid were drawn repeatedly, and concentrations were determined by HPLC. RESULTS: Maximum serum concentrations (Cmax) ranged from 211 to 426 mg/L (median, 302 mg/L). The volume of distribution was 0.34 to 0.86 L/kg body weight (median, 0.53 L/kg), and the elimination half-life in serum (t1/2beta) 3.22 to 8.44 hours (median, 4.53 hours). Cerebrospinal fluid Cmax values ranging from 0.68 to 34.14 mg/L (median, 3.88 mg/L) were observed 1 to 12 hours after the end of the tromethamine infusion (median, 2 hours). AUC(CSF)/AUC(S) as a measure of overall cerebrospinal fluid penetration was 0.015 to 0.46 (median, 0.068). Cerebrospinal fluid Cmax and AUC(CSF)/AUC(S) depended on the function of the blood-cerebrospinal fluid barrier. Cerebrospinal fluid t1/2 (8.52 to 14.2 hours; median, 11.2 hours) was substantially longer than the t1/2beta in serum. In vitro, cerebrospinal fluid concentrations < or =30 mg/L did not influence cerebrospinal fluid pH. CONCLUSION: Tromethamine cerebrospinal fluid concentrations will be high enough to increase the pH of the cerebrospinal fluid only at large doses and in patients with a pronounced disruption of the blood-cerebrospinal fluid barrier.

Lumbar and ventricular CSF protein, leukocytes, and lactate in suspected bacterial CNS infections.

Protein concentration, leukocyte density, and lactate concentration were studied in 41 pairs of ventricular and lumbar CSF drawn at an interval of less than 24 hours from patients with suspected bacterial CNS infections. The ventriculo-lumbar ratios ranged from 0.003 to 10.2 (median=0.42) for protein and from 0.002 to 53.5 (median=0.17) for leukocytes. The uneven distribution of leukocytes and proteins in the CSF space may produce findings that fail to indicate bacterial CNS infections. Lactate was distributed more homogeneously in the CSF space than protein and leukocytes (ventriculo-lumbar ratio 0.52 to 1.66 [median=0.811).

Inflammatory central nervous system demyelination: correlation of magnetic resonance imaging findings with lesion pathology.

Magnetic resonance imaging (MRI) is widely used to evaluate and monitor disease activity in inflammatory demyelinating central nervous system (CNS) diseases such as multiple sclerosis. The present study aimed at correlating MRI findings with histological parameters in 6 cases of biopsy-proven inflammatory demyelination of the CNS. The earliest stages of demyelinating activity manifested as almost isointense lesions with a massive gadolinium-DTPA (Gd-DTPA) enhancement in T1-weighted scans. In T2-weighted scans, early active lesions formed a border of decreased intensity compared with the lesion center and the perifocal edema. The morphological correlate of this pattern in our patients was activated macrophages in the zone of myelin destruction at the plaque border. Late active lesions were hypointense in T1 and hyperintense in T2 scans. Inactive demyelinated and remyelinating lesions were hyperintense in T2 scans and enhanced inhomogenously after Gd-DTPA application. T1 scans revealed major differences in the degree of hypointensity that correlated with the extent of axonal damage, extracellular edema, and the degree of demyelination or remyelination.

Critical levels of spinal cord blood flow and duration of ischemia for the acute recovery of segmental spinal cord responses in cats.

A broad range of residual lumbar spinal cord blood flows assessed by laser-Doppler flowmetry (rSCBF, 0-78%) was achieved by snare occlusion of the descending aorta and additional blood-volume reduction for 1-10 min in spinal cats (n = 30; 238 trials). The period of complete reflex suppression (delay until recovery) that revealed some correlation to duration (r = 0.72) and depth (r = -0.36) of ischemia showed comparable durations in mono- and polysynaptic reflexes, whereas it was significantly less for the cord dorsum potential (CDP). With rSCBF values > 50-60% reflexes and > 45%, the CDP was rarely abolished, irrespective of the duration of ischemia. The threshold of duration for a complete loss of reflex responses was found to be approximately 1 min of ischemia. The influence of rSCBF and duration of ischemia on the occurrence of incomplete recoveries of reflexes was assessed simultaneously in a logistic regression model. Compared with periods of ischemia of 3 min, all longer durations showed a steep risk gradient for incomplete recoveries; an increment of 10% in rSCBF led to a risk reduction for incomplete recoveries of nearly 25%. These findings were significant (p < 0.001) and indicated that blood-flow thresholds and limits for the development of neurologic deficits of the spinal cord are comparable to those of the brain, with the important difference that the blood-flow reserve of the spinal cord is smaller.

Kinetics of piperacillin and tazobactam in ventricular cerebrospinal fluid of hydrocephalic patients.

Its broad antibacterial spectrum qualifies the combination of piperacillin and tazobactam for therapy of nosocomial bacterial central nervous system (CNS) infections. Since these infections sometimes are accompanied by only minor dysfunction of the blood-cerebrospinal fluid (CSF) barrier, patients with noninflammatory occlusive hydrocephalus who had undergone external ventriculostomy were studied (n = 9; age range, 48 to 75 years). After administration of the first dose of piperacillin (6 g)-tazobactam (0.5 g) over 30 min intravenously, serum and CSF were drawn repeatedly and analyzed by high-performance liquid chromatography. Pharmacokinetics were determined by noncompartmental analysis. Maximum concentrations of piperacillin in CSF ranged from 8.67 to <0.37 mg/liter (median, 3.42 mg/liter), and those of tazobactam ranged from 1.37 to 0.11 mg/liter (median, 0.45 mg/liter). CSF maxima were observed, in median, 1.5 and 2 h after the end of the infusion. Elimination in CSF was considerably slower than in serum (median half-life at beta phase for piperacillin, 5.9 h in CSF versus 1.47 h in serum; for tazobactam, 6.1 h versus 1.34 h). For tazobactam, the ratio of the area under the concentration-time curve (AUC) in CSF to the AUC in serum was approximately three times as high as that for piperacillin (medians, 0.106 versus 0.034). In view of the tazobactam concentrations in CSF observed in this study, the practice of using a constant concentration of 4 mg of tazobactam per liter for MIC determination is inadequate for intracranial infections. Larger amounts of tazobactam than the standard dose of 0.5 g three times daily may be necessary for CNS infections.

Influence of short-term ischemia on segmental spinal cord reflex functions in cats.

In the lumbar spinal cord in cats, microcirculatory (laser Doppler flowmetry) and segmental neurophysiological parameters [monosynaptic reflexes of a flexor and extensor, polysynaptic reflexes from a cutaneous nerve, and the cord dorsum potential (CDP)] were determined in context with ischemias of 1-10 min. Ischemias were achieved by aortic snare occlusion of the descending aorta and were pooled into deep and moderate ones (0-20% and 20-50% residual spinal cord blood flow). Three phases of reaction to ischemia were defined: a period of decreasing responses, a period of delay until recovery, and a recovery period from beginning to completeness of recovery. Although the period of decreasing responses was relatively constant, the delay until recovery could be correlated with duration and depth of ischemia. The recovery period depended mainly on the duration of ischemia. For 2-6-min ischemias, the correlation between depth and duration of ischemia to the delay until recovery or to the recovery period tended to be linear. The period of decreasing responses, the delay until recovery, and the recovery period of mono- and polysynaptic reflexes behaved in a comparable way and demonstrated similar susceptibility to ischemia. The CDP turned out to be the most stable response, indicating a higher resistance of the first-order interneurons to ischemia than of motor neurons.

Slow elimination of mannitol from human cerebrospinal fluid.

OBJECTIVE: The rise of intracranial pressure above the pre-treatment level (rebound phenomenon) is considered, in part, a consequence of osmotherapeutics penetrating into the intracranial compartments. METHODS: The kinetics of mannitol in the ventricular CSF were studied in 10 patients with cerebrovascular stroke after a single i.v. infusion of 37.5 g over 15 min. RESULTS: Maximum mannitol CSF concentrations (mean = 51.1 mg.1-1) were reached 2-12 h after termination of the infusion. Mean t1/2CSF (18.3 h) by far exceeded t1/2S (3.71 h). AUCCSF/AUCS, as a measure of mannitol CSF penetration, ranged from 0.037 to 0.390. CONCLUSION: The slow elimination of mannitol from CSF implies a high risk of accumulation in the central nervous compartments after repeated dosing.

Interstitial adenosine and serotonin in the feline lumbar spinal cord during short-term ischaemia.

During controlled ischaemia (aortal snare occlusion) of the lumbar spinal cord, microcirculatory (laser-Doppler flowmetry) and segmental neurophysiological parameters (monosynaptic reflexes, polysynaptic reflexes, cord dorsum potential=CDP) as well as interstitial concentrations of adenosine and serotonin (5-HT) were determined in the grey matter using the microdialysis/HPLC method. Ischaemic periods of 1-7 min with a residual blood flow in the lumbar spinal cord of 10-30 % of the preischaemic control blood flow caused a blockade of spinal pathways and an increase of concentrations of interstitial adenosine and 5-HT. This increase started immediately after the initiation of the ischaemic period and reached a maximum at the end or shortly after the end of the ischaemic period during postischaemic hyperaemia. A close correlation between the duration of ischaemia and the interstitial concentration of adenosine and 5-HT was not found. Repetition of ischaemic periods in an experiment did not lead to an extracellular accumulation or an exhaustion of the release of 5-HT, whereas some indication was found for an exhaustion of adenosine release. The course of the increase of interstitial adenosine and 5-HT was partly found to correlate to the loss and recovery of the CDP following ischaemia. The concentrations usually reached control levels before spinal reflexes reappeared. The highly dynamic changes in concentrations of adenosine and 5-HT in the extracellular space of the spinal cord during and after short-term ischaemia revealed some relation to the time course of recovery of segmental spinal functions by reflecting the course of spinal neuronal metabolism.

Cerebrospinal fluid ceftazidime kinetics in patients with external ventriculostomies.

Ceftazidime has proven to be effective for the treatment of bacterial meningitis caused by multiresistant gram-negative bacteria. Since nosocomial central nervous system infections are often accompanied by only a minor dysfunction of the blood-cerebrospinal fluid (CSF) barrier, patients with noninflammatory occlusive hydrocephalus who had undergone external ventriculostomy were studied (n = 8). Serum and CSF were drawn repeatedly after the administration of the first dose of ceftazidime (3 g over 30 min intravenously), and concentrations were determined by high-performance liquid chromatography by using UV detection. The concentrations of ceftazidime in CSF were maximal at 1 to 13 h (median, 5.5 h) after the end of the infusion and ranged from 0.73 to 2.80 mg/liter (median, 1.56 mg/liter). The elimination half-lives were 3.13 to 18.1 h (median, 10.7 h) in CSF compared with 2.02 to 5.24 h (median, 3.74 h) in serum. The ratios of the areas under the concentration-time curves in CSF and serum (AUCCSF/AUCS) ranged from 0.027 to 0.123 (median, 0.054). After the administration of a single dose of 3 g, the maximum concentrations of ceftazidime in CSF were approximately four times higher than those after the administration of 2-g intravenous doses of cefotaxime (median, 0.44 mg/liter) and ceftriaxone (median, 0.43 mg/liter) (R. Nau, H. W. Prange, P. Muth, G. Mahr, S. Menck, H. Kolenda, and F. Sörgel, Antimicrob. Agents Chemother. 37:1518-1524, 1993). The median AUCCSF/AUCS ratio of ceftazidime was slightly below that of cefotaxime (0.12), but it was 1 order of magnitude above the median AUCCSF/AUCS of ceftriaxone (0.007) (Nau et al., Antimicrob. Agents Chemother. 37:1518-1524, 1993). The concentrations of ceftazidime observed in CSF were above the MICs for most Pseudomonas aeruginosa strains. However, they are probably not high enough to be rapidly bactericidal. For this reason, the daily dose should be increased to 12 g in cases of P. aeruginosa infections of the central nervous system when the blood-CSF barrier is minimally impaired.

Ketamine for analgosedative therapy in intensive care treatment of head-injured patients.

Ketamine was supposed to be contra-indicated in head injured patients although it possesses numerous advantages over other commonly used analgosedative drugs. Referring to these potential advantages and the lack of definitive data about its effect upon ICP, CPP or neurological development, we conducted a prospective study in which moderate or severely head injured patients (n = 35) were prospectively allocated to receive treatment either with a combination of ketamine or midazolam or fentanyl and midazolam. The initial dose was 6.5 mg/kg/day midazolam, 65 mg/kg/day ketamine or 65 micrograms/kg/day fentanyl and was later adjusted due to clinical requirements for a period of 3 to 14 days. Comparably high dosages of ketamine [corrected] have been found necessary (104 mg/kg/day). Four patients from the ketamine group (n = 17) and 5 from the control group (n = 18) were withdrawn during treatment due to persistent ICP above 25 mm Hg, countermeasured by barbiturate coma. Two more patients were withdrawn due to development of cardiovascular arrest (ketamine group) and multi organ failure. A comparison of the remaining patients revealed a lower requirement of catecholamines (significant on first day, p<0.05), an on average 8 mm Hg higher cerebral perfusion pressure and a 2 mm Hg higher intracranial pressure in the study [corrected] group. Enteral food intake was better in the study group. The outcome was comparable in both groups with or without inclusion of withdrawn patients.

Shunt-valve noise as an unusual reason for shunt revision.

A 29-year-old male patient suffering from communicating hydrocephalus was treated by placement of a ventriculoatrial shunt (Pudenz-Heyer bur-hole valve). A disturbingly loud, pulse-synchronous, bruit in the ear on getting up from lying down remained unrecognized for 3 years as possibly generated by air bubbles in the valve. Clinical and technical investigations by a phonocardiographic and a transcranial Doppler device demonstrated that the noise was a functional indicator of shunting activity, relying on intracranial pressure conductional on arterial blood pressure as determined by its close relationship to the cardiac cycle. When this phenomenon was looked for, it was detected in three other patients, one of whom saw it as a shunt-function indicator.

Kinetics of ofloxacin and its metabolites in cerebrospinal fluid after a single intravenous infusion of 400 milligrams of ofloxacin.

Ofloxacin has been reported to diffuse readily into the cerebrospinal fluid (CSF) in subjects with both inflamed and uninflamed meninges. However, with moderately susceptible bacteria, ofloxacin concentrations in CSF may be subtherapeutic after administration of an intravenous (i.v.) dose of 200 mg. For this reason, the kinetics of a higher dose of ofloxacin in CSF was studied with humans. Six patients with occlusive hydrocephalus caused by cerebrovascular diseases who had undergone external ventriculostomy received 400 mg of ofloxacin i.v. over 30 min. Serum and CSF samples were drawn repeatedly. Serum from 12 healthy volunteers was sampled repeatedly after they had received 400 mg of ofloxacin i.v. over 60 min. Ofloxacin, ofloxacin-N-oxide, and N-desmethyl-ofloxacin concentrations were determined by high-pressure liquid chromatography with fluorescence detection. The maximum ofloxacin concentrations in the serum of the patients ranged from 7.36 to 11.6 mg/liter (mean, 9.55 mg/liter), the apparent volume of distribution/body weight was 0.96 to 1.19 liters/kg (mean, 1.11 liters/kg), and the total body clearance was 115 to 280 ml/min (mean, 192 ml/min). In healthy volunteers, the volume of distribution/body weight and the total body clearance were higher and amounted to 1.27 +/- 0.18 liters/kg and 217 +/- 43 ml/min (means +/- standard deviations), respectively. These differences were attributed to the older ages of the patients than the volunteers. In the CSF of patients, maximum concentrations of 1.00 to 2.85 mg/liter (mean, 2.04 mg/liter) were observed 0.5 to 4 h following the completion of the ofloxacin infusion. Ofloxacin elimination from CSF was slightly slower than that from serum (half-lives, 4.33 to 10.02 versus 4.27 to 9.14 h). The overall penetration of ofloxacin into CSF, as expressed by the ratios of the areas under the concentration-curves, amounted to 0.59 to 0.81 (mean, 0.65). The more hydrophilic metabolites ofloxacin-N-oxide and N-desmethyl-ofloxacin passed less readily than ofloxacin into the CSF. In conclusion, the concentrations in CSF attained after a single i.v. infusion of 400 mg of ofloxacin in the absence of meningeal inflammation appear to be high enough to inhibit the growth of most staphylococci and members of the family Enterobacteriaceae, which are often involved in CSF shunt infection. Yet, in view of pharmacodynamic studies suggesting a peak concentration in CSF of at least 10-fold the MIC, the use of ofloxacin for central nervous systems infections is optimal only with highly susceptible pathogens (MIC, less than or equal to 0.12 mg/liter).

Passage of cefotaxime and ceftriaxone into cerebrospinal fluid of patients with uninflamed meninges.

Cefotaxime and ceftriaxone have proven to be effective in pyogenic infections of the central nervous system. Since in some bacterial central nervous system infections the blood-cerebrospinal fluid (CSF) barrier is either minimally impaired or recovers in the course of the illness, we studied the penetration of both antibiotics in the absence of inflamed meninges. Patients who had undergone external ventriculostomies for noninflammatory occlusive hydrocephalus received either cefotaxime (2 g/30 min) or ceftriaxone (2 g/30 min) to treat extracerebral infections. Serum and CSF were drawn repeatedly after the first dose. With ceftriaxone, they were also drawn after the last dose. The concentrations of cefotaxime, its metabolite desacetylcefotaxime, and ceftriaxone were determined by high-performance liquid chromatography with UV detection. Maximum concentrations of cefotaxime in CSF were reached 0.5 to 8 h (median = 3 h; n = 6) after the end of the infusion and ranged from 0.14 to 1.81 mg/liter (median = 0.44 mg/liter; n = 6). Maximum levels of ceftriaxone in CSF ranging from 0.18 to 1.04 mg/liter (median = 0.43 mg/liter; n = 5) were seen 1 to 16 h (median = 12 h; n = 5) after the infusion. The elimination half-life of cefotaxime in CSF was 5.0 to 26.9 h (median = 9.3 h; n = 5), and that of ceftriaxone was 15.7 to 18.4 h (median = 16.8 h; n = 3). It is concluded that after a single dose of 2 g, maximal concentrations of cefotaxime and ceftriaxone in CSF do not differ substantially. The long elimination half-lives guarantee uniform concentrations in CSF. These concentrations reliably inhibit highly susceptible bacteria but cannot be relied on to inhibit staphylococci and penicillin G-resistant Streptococcus pneumoniae.

["Endogeniform" affective psychoses and normal pressure hydrocephalus]. / "Endogeniforme" affektive Psychosen und Normaldruckhydrozephalus.

Four patients with neuroradiological evidence of normal pressure hydrocephalus and psychiatric diagnosis of affective psychoses with major depression--like characteristics are presented. Three patients underwent shunting operations following an observation period of 2 to 6 years. During the post-operative follow-up of 3 to 7 years, resp., no clinical changes were noted. In our opinion, and following critical evaluation of the available literature, major depression--like affective disorders in normal-pressure hydrocephalus are not influenced by shunting operations, unless they occur simultaneously as an additional symptom in an Adams-Hakim syndrome with definite progression.