Age-dependence of cerebrospinal parameters.

OBJECTIVE: The records of 159 patients were reviewed who routinely underwent a classical volume-pressure testing procedure due to suspected cerebrospinal fluid circulatory disorders. METHODS: Regression analyses were carried out to explain the cerebrospinal parameters' relationships to age. Least median squares (LMS) algorithms achieved robust estimation of simple linear model parameters. Also, method of weighted regression was used because of unequal variances in the observations. RESULTS: Cerebrospinal elastance and resistance to outflow revealed significant LMS regressions: y = 0.171x + 7.460 (n = 159, p < 0.0001) and y = 0.096x + 1.871 (n = 97, p < 0.0001), respectively. Similarly, weighting data resulted in models such as y = 0.151x + 6.830 (p < 0.0001) for elastance and y = 0.087x + 1.730 (p < 0.0001) for resistance estimates. The intracranial pressure at rest showed no age-related dependency. Both clear clinical and morphological signs were found in 20% of patients. CONCLUSION: Expecting no time-variant properties we surprisingly found a significant linear relationship in cerebrospinal parameters and age. Thus, parameter magnitudes are not likely dominated by a pathological process only but also determined by temporal system alterations.

Artificial elevation of brain tissue glycerol by administration of a glycerol-containing agent. Case report.

In recent years the development of secondary brain damage and derangement of neurochemical parameters after severe head injury has been monitored using microdialysis. Provided the blood-brain barrier is intact, glycerol is regarded as a potential marker for membrane phospholipid degradation. The authors report a case in which marked elevation of interstitial glycerol was induced after exogenous administration of a glycerol-containing agent. A 25-year-old man was injured in a motorcycle accident and was admitted to the authors' institution with a unilateral dilated and fixed pupil and a Glasgow Coma Scale score of 3. Computerized tomography scans revealed a large subdural hematoma on the left side, subsequent midline shift, and generalized edema. Emergency craniotomy was performed for evacuation of the hematoma. The patient was prepared for multisensory monitoring and a microdialysis catheter was inserted into his left frontal lobe. After a routine enema containing 85% glycerol had been administered, the authors measured a marked increase in glycerol in the dialysate. This occurred while the patient was in as stable a condition as could be expected given the circumstances. The increase in interstitial glycerol in the injured tissue was most likely due to an impaired blood-brain barrier. Thus, the interstitial glycerol concentration had been corrupted by exogenous glycerol, and the marker properties of glycerol in this case became questionable. Consequently, administration of glycerol, which is frequently found in various infusions and emulsions, can promote secondary brain damage by adversely shifting osmotic gradients.

[Initiation of rehabilitation after surgery for herniated lumbar disk: pilot study of efficacy from the viewpoint of the surgical hospital]. / Einleitung der Rehabilitation nach lumbaler Bandscheibenoperation: Pilotstudie zur Entscheidungsfindung aus Sicht der operierenden Klinik.

The initiation of rehabilitation after lumbar disc surgery in Germany is up to the operating hospital. A decision between outpatient and inpatient rehabilitation is possible. Until now this decision is not based on scientific data but on the individual experience of the hospital. This prospective study compares the effect of outpatient and inpatient therapy: In 65 patients medical and psychosocial data were collected shortly before operation, 1 week and 6 months after surgery. Of these patients, 42 underwent inpatient, 21 outpatient rehabilitation, 2 patients renounced rehabilitation. The outpatient and inpatient rehabilitation groups showed no significant difference in testing before or shortly after the operation concerning subjective state of health and somatic findings. Some 6 months later, long term outcome was identical, i.e. the groups did not differ in psychosocial or medical respects. However, the inpatient rehabilitation group had taken significantly longer to return to work. This pilot study stresses the importance of further research on rehabilitation after lumbar disc surgery. It should be shared by surgeons and rehabilitation experts.

Treatment of elevated intracranial pressure by infusions of 10% saline in severely head injured patients.

The management of intracranial pressure (ICP) is a factor in outcome of patients with head trauma. However, recent studies have revealed that the current strategies, which have been applied to control ICP for adequate cerebral perfusion, are unsatisfactory. Against this background, the efficacy of short-term infusions of hypertonic saline on ICP was investigated. In severely head injured (SHI) patients, hypertonic saline (100 ml 10% NaCl) was administered when standard agents (mannitol, sorbitol, THAM) failed in reducing ICP. To evaluate the pressure reduction after saline infusions the resulting ICP relaxations were analysed statistically in respect to the parameters amplitude, duration and dynamic behaviour of the ICP responses. In 42 randomized relaxations, the relative ICP decrease was 43% [28%-58%] (median [interquartile range]). The corresponding pressure drop was 18 mmHg [15-27 mm Hg]. Relaxations lasted for 93 min [64-126 min] and a relative ICP minimum was reached 26 min [12-33 min] after infusion. In the individual cases the temporal course of the parameters amplitude and decline interval depict a tendency toward lower and higher values, respectively, under conditions of a generally increasing ICP. As expected, the infusion of hypertonic saline reduces ICP in patients suffering from SHI. The pressure drop, duration and dynamic behaviour are suspected to depend both on the pressure level to reduce and concomitant medications.

PET and CBF studies of chronic hydrocephalus: a contribution to surgical indication and prognosis.

The authors investigate whether measurement of cerebral blood flow (CBF) in chronic hydrocephalus is a reliable indicator in selecting patients to undergo ventriculoperitoneal shunting. Global and regional CBF is quantified (Kety-Schmidt one-compartment model) by positron emission tomography in 21 patients. CBF is determined following injection of 15O-H2O at three time points: 1 week before, 7 days after, and 7 months after shunting. The neurological status of these patients is classified, and cerebrospinal fluid (CSF) dynamics continuous intracranial pressure [ICP] monitoring and CSF infusion tests) were assessed prior to surgery. Preoperative global CBF values correlate well with clinical outcome. Patients with a significantly lower global CBF value show clinical improvement after 7 months, whereas patients with higher CBF values do not (mean, 33 vs. 45 ml/100 ml per minute; p < 0.05). In contrast to conventional methods, including long-term ICP measurement and CSF infusion tests, preoperative global CBF values are discriminating in terms of clinical outcome. Thus, measurement of CBF may be helpful in evaluating the ultimate utility of shunt therapy in chronic hydrocephalus.

Cerebral blood flow in chronic hydrocephalus--a parameter indicating shunt failure--new aspects.

Prediction of outcome after shunt-therapy in chronic hydrocephalus syndrome is uncertain. Pathology reveals an impairment of cerebral blood flow (CBF). Based on this, we evaluated CBF and its significance for the assessment of prognosis. In 21 patients (mean age 69 years) selected for surgery, CBF was measured by PET (15O-H2O) before, about one week and 7 months (n = 14) after shunting. CBF was computed by a 1-compartmental model in the territories of the ACA, MCA and PCA. One PET slice in the height of the maximum projection of both cellae mediae was chosen. CBF data were standardized by cluster analysis. Three CBFClusters with significantly different CBF levels prior to shunting in the ACA, MCA and PCA territory, respectively, referred to the sample average (38.2 ml/100 ml/min) were found. These CBFClusters differed in clinical outcome: almost 50% and 90% of patients improved clinically in CBFCluster I, with a perfusion level lower than average, after one week and 7 months, respectively. In contrast, patients of CBFCluster II with an average perfusion did not improve. CBF changes 7 months after shunting related to global CBF before surgery showed a relationship with the clinical course. Clinical outcome corresponded with preoperative global CBF values. Cerebral blood flow lower than average forecasts clinical improvement. Our results suggest that measurement of CBF adds to the indication for surgery.

Clinical predictors of the psychosocial long-term outcome after brain injury.

The correlation of clinical with psychological and social data is an attempt to find predictors of the definite long-term outcome after brain injury. 34 patients were reexamined 3 to 8 years after the accident using a number of psychological tests. Additionally, life quality was defined and evaluated. Only patients with an initial Glasgow Coma Scale-Score of 3-12, an intracranial traumatic lesion on computertomography and age 16-65 years at the time of accident were included in this study. Patients exhibited a uniform pattern of disturbances in psychosocial long-term outcome. These disturbances were compared with initial clinical data: memory, attention and learning were significantly correlated with the duration of coma and the presence of additional extracerebral injuries. From the initial computerized tomography, the findings 'compression of basal cisterns' and 'intracerebral contusion' showed to be predictors of the cerebral function. Late social status and behavior, defined as quality of life, were clearly related with initial clinical findings. In conclusion, there are early clinical predictors of the long term social and psychological outcome after brain injury.

On the effect of calcium antagonists on cerebral blood flow in rats. A comparison of nimodipine and flunarizine.

To assess the influence of nimodipine treatment in brain tissue at different levels of blood pressure, we estimated the cerebral blood flow using hydrogen clearance. Rats were treated with nimodipine (n = 8), its placebo (n = 10), flunarizine (n = 11) and its placebo (n = 10), and a group of controls (n = 10). Cerebral blood flow was estimated during arterial normo-, hyper- and hypotension. The lowest cerebral blood flow estimates calculated for nimodipine were 43.8 +/- 7.8, 90.9 +/- 13.3, and 33.6 +/- 6.1 ml/min/100 g for normo-, hyper- and hypotension, respectively. Cerebral blood flow in the nimodipine placebo group was 84.1 +/- 10.3, 139.9 +/- 19.9, and 55.2 +/- 10.5 ml/min/100 g. In the flunarizine group, the blood flow was 77.3 +/- 15.2, 144.7 +/- 15.0, and 43.8 +/- 5.9 ml/min/100 g. In the control group, cerebral blood flow was 90.0 +/- 29.1, 143.0 +/- 42.1, and 75.5 +/- 29.8 ml/min/100 g. The low blood flow in the nimodipine group might have been a consequence of brain edema caused by extravasates. Thus impaired blood flow reduces the usefulness of nimodipine in the prevention of vasospasm. Flunarizine is a potential alternative treatment of vasospasm treatment as well as for cerebral blood flow improvement, as shown in our experimental study.

Computed tomographic criteria and survival rate for patients with acute subdural hematoma.

OBJECTIVE: Computed tomographic data from 174 patients with acute subdural hematoma were analyzed statistically to identify parameters that could be evaluated independently of clinical and neurological status to estimate outcome. METHODS: This retrospective study was made necessary by the fact that the patients admitted usually had been treated with intubation, sedation, and artificial ventilation, which precludes neurological examination. RESULTS: In surgically treated patients, the hematoma thickness ranged from 5 to 35 mm and the midline shift was 0 to 33 mm. In 81 patients (46.6%), the hematoma thickness was greater than the midline shift; in 24 patients (13.8%), the hematoma thickness equaled the midline shift; and in 69 patients (39.6%), the midline shift exceeded the hematoma thickness. Of the patients, 52% died after surgery, for 29% we obtained good or satisfying results, and 19% were in poor condition after therapy. The Kaplan-Meier survival analysis proved that the survival rate was only 50% for a hematoma thickness of approximately 18 mm and a midline shift of 20 mm. The survival function dropped markedly for midline shifts of more than 20 mm and converged to 0% for midline shifts of more than 25 mm. If the midline shift exceeded the hematoma thickness by 3 mm, the survival function was 50%; when the midline shift exceeded the hematoma thickness by 5 mm, the survival function was 25%. The Glasgow Outcome Scale scores were correlated significantly with these parameters. The parameters, which are the measured hematoma thickness, the midline shift, and the difference between the hematoma thickness and the midline shift, allow robust/adequate estimation of survival function and outcome for patients suffering from acute subdural hematoma. CONCLUSION: Based on these data, indications for surgery could be assessed by means of video conferencing, i.e., without personal examination of the patients.

The effect of mannitol and nimodipine treatment in a rat model of temporary focal ischemia.

Male Sprague Dawley rats were anesthetised with Xylazine and Ketamine intraperitoneally. After a lateral craniotomy the cerebral inferior vein was ligated and a very small clip (Biemer clip) was placed on the MCA near its origin for 1 hour. This procedure induced a focal infarction in 100% of the rats. After removal of the clip the lumen of the MCA was patent. The study was divided in 3 randomized groups (control group n = 15; Nimodipine group n = 11, treatment 30 micrograms/hour/kg body-weight; Mannitol group n = 15, treatment 5.4 ml/hour/kg body-weight). Besides heart-rate, ECG and blood pressure we measured the extracellular potassium and calcium concentration with ion-selective microelectrodes; the ICBF was estimated by laser-doppler-flowmeter. The MCA was clipped for 1 hour. After 1 hour of reperfusion the brain was fixated and the volume of infarction was measured by serial slices. Nimodipine or Mannitol treatment started 5 min before clipping the MCA. In rats with Nimodipine treatment the extracellular calcium starts at a significantly higher level (2.3 +/- 0.5 mmol/l) and the decrease during ischemia remains above a level of 1.2 +/- 0.2 mmol/l. The increase in potassium during ischemia and Nimodipine (calculated in change of concentration/time [dc/dt]) is significantly slower than in the control group. In contrast to the post-ischemic hyper- and hypoperfusion in the control group the reperfusion in the Mannitol group is nearly normal. In the control group the infarction volume is 20% of the brain, in the Nimodipine group 15% and in the Mannitol group only 11%. The calcium antagonist Nimodipine and the free-radical scavenger Mannitol therefore promise to be a way to treat or prevent temporary focal cerebral ischemia.

Testing the hydrocephalus shunt valve: long-term bench test results of various new and explanted valves. The need for model for testing valves under physiological conditions.

13 new and 19 explanted hydrocephalus shunt valves were tested under perfusion for two weeks, using a modified ASTM test. Some manufacturers seem to have problems with quality control. Our results show large deviations in pressure-flow-characteristics in different valves, in some cases leading to an extremely high pre-shunt pressure. Test results almost corresponding to manufacturer's specifications were found in diaphragm valves and in some ball and spring valves. Results from slit valves usually varied widely, some being good, but others bad (much too high a pressure) or dangerous with even possibly fatal characteristics. Whilst laboratory performance may not correlate with clinical results, due to different impact of cerebrospinal fluid (CSF) pressure and flow on hydrocephalus shunting systems, manufacturers should provide devices that meet their supposed specifications. We developed an apparatus allowing simulation of different CSF production rates, CSF outflow resistances, CSF pressure waves caused by arterial and venous pulsation, breathing and coughing, and hydrostatic differential pressure caused by body position changes. This model enables testing of shunt valves under almost physiological conditions, thus closing the gap between conventional bench test results and clinical performance of hydrocephalus shunt valves.

[The effect of acetazolamide-induced, endogenous volume stress of the cerebrospinal system on intracranial pressure. Diamox--effect on intracranial pressure]. / Die Wirkung der Acetazolamid-induzierten, endogenen Volumenbelastung des zerebrospinalen Systems auf den intrakraniellen Druck. DIAMOX--Wirkung auf den intrakraniellen Druck (ICP).

In 16 patients with possible disturbed CSF circulation longterm recording of intracranial pressure (ICP) was performed. In 9 of the 16 patients the disorder became evident after the application of an exogenous volume-pressure testing procedure. This procedure enabled a classification into a group I--disturbed CSF circulation (8 patients)--and another group II--normal CSF circulation (8 patients). During a routine Xenon-CT-CBF study all patients of both groups were given to 1 g acetazolamide (DIAMOX) intravenously. Before, during and after the administration of DIAMOX the epidural ICP was continuously measured. An increase in ICP was monitored in all patients. In group I the average initial ICP was 13.6 +/- 7.6 mmHg. The maximum ICP was reached within a time interval of 13.1 +/- 4.5 min after DIAMOX administration. At this time the mean ICP was 36.4 +/- 19.2 mmHg (p less than 0.01). The average initial ICP in group II was 6.3 +/- 4.2 mmHg. The maximum ICP was reached within a time interval of 13.6 +/- 1.1 min. At this time the mean ICP was 11.9 +/- 4.8 mmHg (p less than 0.01). In respect to the maximum ICP both groups were significantly different (p less than 0.01). Despite a considerably rising ICP up to values of about 50 to 70 mmHg in several patients of group I only 1 patient complained of being sick. Presumingly, an ICP elevation caused by vasodilatation would be better tolerated than ICP elevations due to other causes.

Traumatic brain swelling and operative decompression: a prospective investigation.

Since 1978, decompressive craniotomy was performed according to a standardized protocol. Exclusion criteria were age greater than or equal to 40 years, deleterious primary brain damage, operable space occupying lesions, larger infarctions in CT scan or irreversible brain stem incarceration/ischaemic damage as shown by bulbar syndrome, loss in BAEP or oscillating flow in TCD. Indication was given by progressive intracranial hypertension not controllable by conservative methods, if ICP decompensation was correlated with clinical (GCS, extension spasms, mydriasis) and electrophysiological (EEG, SEP, CCT) deteriorations. 18 patients were decompressed by unilateral. 19 by bilateral craniotomy with large fronto-parieto-temporal bone flap and a dura enlargement by use of temporal muscle/fascia. 37 patients at an age of 18 +/- 7 (4-34) years were operated 5 h-10 d after trauma. Recovery was surprisingly good: only 5 died, 2 due to an ARDS; 3 remained vegetative, all others achieved full social rehabilitation or remained moderately disabled. The best predictor of a favourable outcome was an initial posttraumatic GCS greater than or equal to 7. These in younger patients with delayed posttraumatic decompensation before irreversible ischaemic damage occurs.

A comparative analysis of THAM (Tris-buffer) in traumatic brain oedema.

The effect of THAM on brain oedema parameters was initially investigated in animals with cold brain lesions; THAM was then used in head injury patients, ICP, SAP and CPP were analyzed. In the experiments with rats after freezing lesion, THAM was compared to equivalent doses of Na-bicarbonate. The animals were artificially respirated and sacrificed 6 h after trauma. THAM did significantly reduce water (wet-dry weight technique) and sodium contents in both hemispheres, whereas bicarbonate was ineffective. The potassium contents were even preserved at almost normal levels. In 80 patients receiving alternatively THAM (18-36 g/100-200 ml/1-2h), mannitol (20%, 125-250 ml/20-40 min) or sorbitol (40%, 70-140 ml/20-40 min), the ICP rapidly decreased following THAM infusion. The maximal fall in ICP (33%) was equal to that with mannitol and sorbitol. The slope of ICP decrease was equal with THAM and Mannitol but steeper with sorbitol. With THAM, however, the effect on ICP lasts longer than with osmotherapy. The EEG improved more rapidly after THAM. As shown by blood plasma values, the action of THAM is not based on osmotic effects. The increases in pH and especially in base excess suggest an intracerebral buffering. The encouraging results with THAM require a randomized clinical trial after severe head injury which is presently prepared.

Chronic cerebrovascular insufficiency on the xenon CT scan.

Several investigators have described CT-negative low flow areas in TIA and stroke patients in the chronic phase. The emission tomographic SPECT image they employed has, in contrast to the xenon CT method, no direct relation to the x-ray transmission CT scan. The aim of our study was to study the phenomenon of CT-negative low flow areas using the xenon CT method, a method especially well suited for such cases. 57 xenon CT examinations were performed in 40 TIA patients. Flow data from brain tissue which appeared to be anatomically intact in a slice 5 cm above the canthomeatal plane were analyzed. In the TIA group, the flow in the gray matter was found to be significantly lower on the clinically affected side: symptomatic side, 61.8 +/- 14.7 ml/100 g/min; asymptomatic side, 66.4 +/- 15.8 ml/100 g/min (p less than 0.001). In the stroke group, the flow in the white matter was also affected; symptomatic side, 31.2 +/- 9.8 ml/100, g/min; asymptomatic side, 35.3 +/- 11.1 ml/100 g/min (p less than 0.01). Gray matter: symptomatic side, 56.1 +/- 11.4 ml/100 g/min; asymptomatic side, 66.0 +/- 11.0 ml/100 g/min (p less than 0.001). The findings indicate that the appearance of CT-negative low flow areas in TIA and stroke patients during the chronic phase is the rule rather than the exception. Flow adaptation to anatomic changes not discernible by CT can be differentiated from clinically relevant flow impairment only by testing the cerebrovascular reserve.

[DNA profile, recurrence rate and progression of superficial G2 cancer of the urinary bladder]. / DNA-Profile, Rezidivrate und Progression beim oberflächlichen G2-Karzinom der Harnblase.

In a retrospective study the prognostic value of flow cytometric DNA analysis was studied in 114 newly diagnosed cases with superficial bladder tumours. G1-tumours were generally diploid, G3-tumours almost exclusively aneuploid. G2-tumours exhibited a bimodal distribution with 50% diploid and 50% aneuploid cases respectively. Recurrence and progression correlated systematically with the ploidy level. Furthermore, the degree of aneuploidy is predictive for proneness to progression.

ICP monitoring.

Within the last two decades, the measurement of intracranial pressure (ICP) advanced from basic research to a useful method in clinical practice. The recording of ICP in clinical diagnosis and therapy requires the knowledge of physical, anatomical and pathophysiological fundamentals, of the different measurement principles and of typical, pathognomonic intracranial pressure patterns. This data will be described in this article. The ICP, and its effects, are based on the anatomy of the almost closed rigid skull which is divided into three "compartments" by pressure-resistent septa (falx, tentorium), and which opens into the spinal dura cavity as a 4th compartment. The pressure is distributed by the CSF, whereby hydrostatic laws must be considered. The brain itself is visco-elastic, and its physical characteristics change in pathological conditions. The pathophysiological effects of intracranial hypertension must be divided into generalized pressure effects and directed pressure actions. The generalized pressure effects are caused by the disturbance of the cerebral blood flow (CBF); their understanding requires the knowledge of the characteristic Pressure-Volume (P/V)-Diagram of the craniospinal space, which can be described by mathematical approximations. The directed actions of an elevated ICP are based on pressure gradients (unequal pressure distribution), which are produced by more rapidly growing local intracranial lesions. These pressure differences cause cerebral mass movements with brain stem incarceration, whereby the "pressure = force per area" - rule must be considered. These anatomical and functional basics are of great importance for the measurement technique; for reliability and safety of ICP registration, the elastic forces of the dura and the brain, the pressure distribution as well as the operative procedure and invasivity of the measurement technique have to be regarded. For clinical routine, less invasive methods using miniaturized transducers for epi- or subdural implantation are favorized above the registration of ventricular pressure, which, however, has its special indications. These problems will be described. Besides a registration of the spontaneous ICP fluctuations, a quantitative determination of the P/V-diagram (compliance, elastance, PVI) and of parameters of the CSF dynamics (resistance, CSF production, Pss) may be useful in clinical practice. In diagnosis, invasive methods with artificial volume load may be used, the techniques will be explained.(ABSTRACT TRUNCATED AT 400 WORDS)