An ecotoxicological view on neurotoxicity assessment.

The numbers of potential neurotoxicants in the environment are raising and pose a great risk for humans and the environment. Currently neurotoxicity assessment is mostly performed to predict and prevent harm to human populations. Despite all the efforts invested in the last years in developing novel in vitro or in silico test systems, in vivo tests with rodents are still the only accepted test for neurotoxicity risk assessment in Europe. Despite an increasing number of reports of species showing altered behaviour, neurotoxicity assessment for species in the environment is not required and therefore mostly not performed. Considering the increasing numbers of environmental contaminants with potential neurotoxic potential, eco-neurotoxicity should be also considered in risk assessment. In order to do so novel test systems are needed that can cope with species differences within ecosystems. In the field, online-biomonitoring systems using behavioural information could be used to detect neurotoxic effects and effect-directed analyses could be applied to identify the neurotoxicants causing the effect. Additionally, toxic pressure calculations in combination with mixture modelling could use environmental chemical monitoring data to predict adverse effects and prioritize pollutants for laboratory testing. Cheminformatics based on computational toxicological data from in vitro and in vivo studies could help to identify potential neurotoxicants. An array of in vitro assays covering different modes of action could be applied to screen compounds for neurotoxicity. The selection of in vitro assays could be guided by AOPs relevant for eco-neurotoxicity. In order to be able to perform risk assessment for eco-neurotoxicity, methods need to focus on the most sensitive species in an ecosystem. A test battery using species from different trophic levels might be the best approach. To implement eco-neurotoxicity assessment into European risk assessment, cheminformatics and in vitro screening tests could be used as first approach to identify eco-neurotoxic pollutants. In a second step, a small species test battery could be applied to assess the risks of ecosystems.

[Subarachnoid hemorrhage: protective hypotension in delayed surgery]. / Emorragia subaracnoidea: ipotensione protettiva nella chirurgia dilazionata.

Systemic hypertension is frequently observed in patients with subarachnoid haemorrhage (SAH). Continuing systemic hypertension might augment the risk of rebleeding and also increase the blood flow and blood volume, resulting in more marked cerebral edema and intracranial hypertension. However, reduction of blood pressure might also decrease cerebral perfusion pressure in patient with an impaired autoregulation and in this way enhance the risk of cerebral ischemia. Anti-hypertensive therapy is not recommended to prevent rebleeding after SAH. The agents of choice for reduction of arterial blood pressure might be mixed alfa and beta adrenergic antagonists and barbiturates.

Retrograde cannulation of the jugular vein: erroneous positioning of the catheter in the subarachnoid space.

This report describes one complication related to retrograde positioning of a catheter in the jugular vein in a patient in a coma resulting from subarachnoid haemorrhage. The catheter was found in the cervical subarachnoid space, as confirmed by radiography with contrast medium. Attention is focused on the fact that this technique, usually performed easily and safely, may occasionally present potentially severe complications.

[Effects of inhalation anesthetics on intracranial pressure and cerebral blood flow velocity]. / Effetti degli anestetici inalatori sulla PIC e sulla velocità di flusso cerebrale.

Inhalation anesthetics diminish cerebrovascular resistance, augmenting cerebral blood flow (CBF) and hematic volume. This may lead to a dangerous increase in intracranial pressure (ICP). It has been observed that isoflurane used in hypocapnia does not appear to cause an increase in ICP equal to that caused by other inhalation anesthetics. The authors aimed to evaluate the effects of isoflurane on ICP and on intracranial vessel reactivity to changes in CO2 using a pulsed intracranial Doppler technique which measures cerebral flow velocity (CFV). A prospective study was performed at the Neurosurgery Clinic of the University of Milan in 10 in-patients due to undergo surgical removal of supratentorial intracranial expansion. Patients were anesthetised with isoflurane 1 MAC in air and O2. The following parameters were monitored: ICP at a spinal subarachnoid level; mean arterial pressure (MAP); cerebral perfusion pressure (CPP); ECG; CFV; EtCO2. The study was subdivided into 5 stages: basal (before induction); hypocapnia lasting 30 min; registration of data for 10 min; stabilisation phase in normocapnia; registration in normocapnia. The results show that during hypocapnia isoflurane causes significant reductions in MAP and CCP whereas ICP and CFV tend to diminish but not significantly. On the contrary, isoflurane in normocapnia causes an increase in ICP and a further and more marked reduction in CPP with a corresponding but not significant increase in CFV. In conclusion, in the light of these results the increase in ICP and the contemporary reduction of MAP would appear to restrict the use of isoflurane in normocapnia in patients with intracranial pathologies.(ABSTRACT TRUNCATED AT 250 WORDS)

[Pathology requiring admission to the neurosurgical intensive care]. / Le patologie che devono essere ammesse in terapia intensiva neurochirurgica.

A patient's admission to an ICU should benefit the patient (either short or long term). Consequently patients admitted to the ICU should be only those neurological-neurosurgical ones with one or more organ failure who need immediate or prolonged therapy with adequate monitoring and technical support not available in other wards. Normally admission depends on may other factors, the most important ones seem to be medico-legal responsibilities of the possible refusal of admission even if due to clinical reasons, organizational problems such as equipment and bed availability. There is a need for pre- and post-surgical monitoring for high risk patients. We routinely admit patients to our ICU according to the following directions: respiratory and or cardio-circulatory failure connected to the neurological pathology, impaired consciousness, neurological signs and symptoms indicating deterioration, loss of airway protective reflexes, seizured in neurological-neurosurgical patients, severe electrolyte, metabolic or nutritional disturbances which may affect the CNS; neurosurgical postoperative control, performance of complex techniques (central venous and arterial catheterization, ICP monitoring), management of multiorgan donors suitable for therapeutic transplant. The groups of pathologies observed in our ICU during 1991 where the follow-up: 442 neurological-neurosurgical patients--head trauma 141 (32%)--cerebral tumours 88 (19.9%)--vasculopathies 135 (30.6%)--others 77 (17.5%). 228 (51.5%) patients stayed for a period less than three days. According to our experience we can affirm that causes for patient's admission to neuro-ICUs are various, the legal organizational reasons have a great importance compared to the clinical ones.

[Post-anesthesia rhabdomyolysis syndrome following muscular stress. 2 case reports]. / Sindrome da rabdomiolisi post-anestetica in seguito a stress muscolare. Descrizione di due casi.

Effort rhabdomyolysis is a syndrome which takes the form of a pathology with different etiopathogenetic stages. General anesthesia may trigger off acute muscular cytolysis which is probably influenced by the inflammatory surgical pathology itself. The observation of two cases of post-anesthetic rhabdomyolysis following muscular stress suggest that the exhaustion of muscle energy reserves and the consequent alteration of the ATP/ADP ratio may act as a trigger mechanism for this syndrome. Its close relationship with malignant hyperthermia makes a precise anamnesis vitally important, especially in relation to recent intense physical effort in patients undergoing emergency surgery for acute pathologies.

Clinical evaluation and long-term follow-up in 16 patients with pseudotumour cerebri.

Medical treatment must be promptly established in patients with pseudotumour cerebri. In fact, even though a spontaneous remission of the symptoms is recognized in the literature, we have not any predictive criteria of future visual impairment.

Cerebral blood flow velocity and cerebrospinal fluid pressure after single bolus of propofol.

The effects of propofol on cerebral blood flow velocity, cerebrospinal fluid pressure, cerebral perfusion pressure and mean arterial pressure were studied during induction in 25 patients scheduled for elective craniotomy. Premedication consisted of only atropine sulphate 0.007 mg/kg (im) 45 min before induction. Measurements were made or derived at time zero and 1, 2, 3, 4 and 5 min after an induction dose of propofol (2.5 mg/kg). Patients were retrospectively stratified into two groups, according to cerebrospinal pressure basal values: (i) lower than 10 mmHg (10 pts) and (ii) higher than 10 mmHg (15 pts). Cerebral blood flow velocity, measured by transcranial Doppler, fell in all the patients, but the reduction was significant at 1, 2, 3 and 4 min only in the group with high CSF pressure, while it never reached the critical value of 10 cm/s. Cerebrospinal fluid pressure and mean arterial pressure decreased in both groups of patients and the fall reached a statistical significance at 1 and 2 min in the group with higher baseline CSF pressure, only at 1 min: a parallel decrease of CPP was recorded, but it was not significant. Thus propofol decreases CSF pressure without hazardous effects on cerebral blood velocity and on cerebral perfusion pressure and seems to be a suitable anaesthetic agent in controlling high cerebrospinal fluid pressure in neuroanaesthesia.

[Prevention of vena cava thrombosis during catheterization. Comparison of calciheparin and defibrotide]. / Profilassi della trombosi venosa cavale in corso di cateterizzazione. Confronto tra calcieparina e defibrotide.

Total intraparenteral nutrition therapy using an endocaval catheter is subject to complications due to the catheter itself and to the onset of phlebothrombosis of the venous district involved. Two groups of patients suffering from abdominal surgical pathologies requiring prolonged postoperative parenteral treatment were subjected to antithrombotic prophylaxis. In the first group of 20 patients, calciheparin u.s. was used and in the second defibrotide in the doses recommended in the literature. Serial lab screening of certain clotting parameters was carried of the brachio-subclavio-caval district. In the calciheparin group, the trend of certain examinations shows, as usual, a change in parameters in agreement with the drug's anticlotting action; in the group treated with defibrotide, the haemostatic balance is respected: the angiographies never showed intimal lesion or phlebothrombosis in either group. The usefulness of correct antithrombotic prophylaxis in these patients is confirmed and it is pointed out that defibrotide is more flexible and handy and that it can be used in patients in whom calciheparin is potentially risk.

[Diffuse traumatic cerebral injuries in children]. / Lesioni cerebrali traumatiche diffuse in età pediatrica.

A consecutive series of 41 patients aged less than 16 and admitted to the Department of Neurosurgery of the University of Milan in the period 1977-1978 following serious cranioencephalic trauma with Glasgow Coma Score (GCS) less than or equal to 7, duration of coma longer than 24 h and CT picture of diffuse lesion has been examined. These patients account for 5% of the paediatric cranial traumas observed in the same period and 66% of those in a state of coma. The CT picture made it possible to split patients into 3 groups: a) those without visible cerebral lesions and with subarachnoid and cisternal spaces present; b) those with small hyperdense lesions due to intraparenchymal or median/paramedian subcortical shearing lesions; c) those with marked constriction or absence of the 3rd ventricle and of the perimesencephalic cisterns. The first two pictures (a, b) were considered to be the expression of diffuse axonal damage, the last (c) of diffuse cerebral swelling. Intracranial pressure was monitored in about 50% of patients. The overall outcome of the series was favourable in more than 68% of cases with total mortality of 26.8%. Analysis of individual tomographic categories, however, showed that whereas the group of patients with diffuse axonal lesion presented nil mortality, those with diffuse cerebral swelling had 52% mortality owing to the onset of refractory intracranial hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

[Cervical vertebral and spinal cord injury in intensive therapy]. / Il trauma vertebro-midollare cervicale in terapia intensiva.

24 of 184 patients with vertebro-medullary trauma admitted to the Neurosurgery Clinic of Milan University in the years 1976-1988 have been examined. A common feature of these was a myelic lesion (transverse, complete or incomplete) at cervical level in which respiratory problems had made a period of intensive care indispensable. The purpose of the research was to assess the reliability of certain parameters in establishing patient prognosis. The following parameters were compared: clinical, objective and instrumental examination for a strictly neurological evaluation and for an evaluation of general condition, quantification of the same clinical examination through two scales, the Sunnybrook Cord Injury Scale (SCIS) for the neurological factor and the APACHE II for general condition, the type of treatment, with the same basic medical-resuscitation treatment. The result of the surgery or non-surgery was considered a posteriori. It is concluded that, in the case of the patients considered (high myelic lesion) the prognosis must be split into two different moments that the patient goes through in succession: the acute phase and the stabilisation phase. In the first phase, in which the vital functions are involved, the SCIS and APACHE II scales (with their sum) have great prognostic value; in the second phase, certain values, already considered on the APACHE II scale, are comparable in all patients and the prognostic problem is based on the other scale (SCIS) and on the adjuvant neurophysiological techniques. The very distinction between the two different phases that the patient traverses appears important also for the purposes of surgical indication.2