Internal carotid artery aneurysms, cranial nerve dysfunction and headache: the role of deformation and pulsation.

Cranial nerve dysfunction and headache may occur with unruptured aneurysms of the cavernous and supraclinoid portions of the internal carotid artery. Nerve deformation (mass effect) and transmitted pulsations have been suggested as pathogenetic mechanisms. Differentiation may be possible by studying effects of endovascular treatment with Guglielmi detachable coils. Symptoms and signs of cranial neuropathy were retrospectively contrasted with angiographic aneurysm volumes before and after treatment in 10 patients. Mean follow-up was 36 months. Symptoms improved in three of four patients with cranial nerve dysfunction and in all patients with headache. None of the other patients, one with cranial nerve dysfunction, and three who were asymptomatic, developed any new symptoms after treatment. Aneurysm volume ranged from 0.1 to 2.7 cm(3 )before and 0.2 to 5.7 cm(3) after treatment; the size thus increased by 15 to 110%, a change which was statistically significant (P=0.004). The consistent increase in aneurysm volume with treatment is not associated with clinical deterioration, suggesting that deformation and displacement play a minor role in cranial neuropathy and that transmitted pulsations may be more important.

Embolisation with Guglielmi detachable coils during the period of increased risk for cerebral vasospasm: early outcome.

In a retrospective study, we investigated whether embolisation of intracranial aneurysms during the spasm period (days 3-14) after subarachnoid haemorrhage carries an increased risk. A comparison was made with patients embolised during the same period but in the first 2 days after the haemorrhage. The two groups compared well except for a higher incidence of posterior circulation aneurysm in the group with delayed treatment. There seems to be no difference in the short-term outcome between the two.

The predictive value of cerebrospinal fluid dynamic tests in patients with th idiopathic adult hydrocephalus syndrome.

OBJECTIVE: To evaluate the predictive value of the cerebrospinal fluid (CSF) tap test and CSF outflow conductance in the selection of patients with the idiopathic adult hydrocephalus syndrome, defined exclusively on a clinical basis, for shunt surgery. DESIGN: A prospective, consecutive case series. All patients were assessed before surgery and at 3 months after shunt placement. Preoperatively, CSF pressure, conductance, and CSF formation rate were assessed by a constant-pressure infusion method. Improvement in gait and cognitive functions after removal of CSF was noted (ie, with the CSF tap test). Postoperatively, the infusion method was used to evaluate shunt function. SETTING: Tertiary, academic referral center. PATIENTS: Thirty-five patients with idiopathic adult hydrocephalus (normal-pressure hydrocephalus) syndrome based on conservative clinical criteria. No predictive tests were used for inclusion. All patients had a typical gait disturbance and a communicating hydrocephalus. Twenty-eight patients also had dementia or incontinence, or both. INTERVENTION: The CSF diversion (Cordis, [Orbis-Sigma]) valve, six patients; Hakim's standard system (Cordis Hakim standard system), 29 patients. OUTCOMES OF SURGERY: Serial videotaping of gait, a comprehensive neuropsychologic battery, and the Bartel index of activities of daily life. RESULTS: Gait was improved in 25 (72%) of the 35 patients, whereas the Bartel index remained unchanged. The conditions of five of seven patients with gait disturbance as the sole symptom improved. The spatial function (37% improved) and the findings from the Fuld object memory tests (29% improved) were significantly improved. Shunt dysfunction could not explain the lack of effect of an operation in the remaining patients. It should be noted that these results obtained at 3 months postoperatively may not be applicable in a long-term perspective. The CSF outflow conductance or CSF tap test were not able to identify those patients who would or would not benefit from a CSF diversion procedure. However patients had a lower conductance and a higher CSF pressure than did control subjects. CONCLUSIONS: Considerable improvement in gait was seen, but cognitive function was little affected. The CSF tap test or conductance does not provide additional information that is necessary to distinguish between patients whose conditions will or will not respond to shunting, when selection for surgery is based on conservative clinical criteria.

Five-year follow-up of nonsecreting pituitary adenomas.

Nowadays, nonsecreting pituitary adenomas are usually operated on by means of a transsphenoidal approach, and the transseptal way is the most widely used. Since 1982 we have been using lateral rhinotomy instead, resecting bone in the piriform aperture up to the orbit to obtain a good intrasellar view during surgery. In all, 48 patients were operated on between 1982 and 1987, and all of them have since been evaluated in a 5-year follow-up. The only recurrence occurred in the only patient previously operated on transcranially. Computed tomography was performed in 44 patients (92%) after an average of 4 years and revealed no signs of tumor in any of them. New pituitary insufficiencies developed in six (12%). An improvement in vision was observed in 38 patients (79%), none of whom suffered an impaired visual field or acuity. The frequency of new hormonal insufficiencies and improvement of vision that we observed in our patients is comparable with that reported by other investigators, but the recurrence rate is lower and the optic nerves and chiasma were never damaged thereby causing an impairment of vision. These benefits can most probably be explained by the surgical approach we used, in which the tumor and surrounding structures are very well visualized because the operative field is broader and closer than it is with the transseptal approach, which is normally used for this kind of tumor.

Radiosensitizing effect of estramustine in malignant glioma in vitro and in vivo.

Estramustine-phosphate (EMP), a combination of nornitrogen mustard and 17 beta-estradiol, has been demonstrated to exert specific antiproliferative effects on human glioma cells in vitro. The cytotoxic effect is, at least partially, mediated by inhibiting microtubule function. In this study the combined effect of EMP and radiation was evaluated in the human glioma cell-lines, 251-MG and 105-MG, in vitro, and in the rat glioma BT4C in vitro and in vivo. In all cell-lines an additive effect of EMP and radiation was obtained in vitro. Assuming equal effect of EMP is obtained in subsequent radiation fractions, the cell kill will be increased from 2-3 to 5-10 logs if delivering 30 fractions of 2 Gy combined with EMP. In the BT4C rat model the combined effect was found to be synergistic. Flow cytometry demonstrated an arrest in G2/M phase in all cell-lines after EMP treatment. This block in G2/M phase in addition to the previously demonstrated induction of free oxygen radicals, and the increase of blood flow with an assumed subsequent increase of oxygenation, might provide an explanation for the observed radiosensitizing effect of estramustine.

Results of the lateral rhinotomy approach in transsphenoidal microsurgery for growth hormone-secreting pituitary adenoma.

The results of transsphenoidal microsurgery for growth hormone (GH)-secreting pituitary adenomas in a series of 47 patients are presented. A modified transsphenoidal approach with lateral rhinotomy was employed for the access to the sphenoid sinus. Remission, defined as mean GH concentration less than 2.5 ng/ml, was achieved in 79% of the patients. Macroadenoma size of the tumour and a GH concentration more than 50 ng/ml were factors unfavourable for the outcome. The experience of the lateral rhinotomy approach in transsphenoidal surgery of acromegaly has been favourable. The distance from the incision to the sella is shorter than in rhinoseptal approaches, where the depth of the operative field is determined by the distance from the nasal spine to the sella. The lateral rhinotomy also allowed an exposure of the sella of adequate width in all patients. These aspects of the procedure facilitated adenoma removal.

Cytotoxic effect and uptake of estramustine in a rat glioma model.

The cytotoxic effect of estramustine-phosphate (EMP) and the uptake in tumor tissue were investigated in a rat glioma model in vitro and in vivo. EMP, a combination of nornitrogen mustard and 17beta-estradiol, is a cytotoxic drug which main target is assumed to be the microtubule system. EMP and its metabolite estramustine (EaM) have a demonstrated anti-tumorous effect on human glioma cells in vitro. The drug uptake in tumor tissue and subsequently also the cytotoxic effect, is believed to depend, at least partially, on a specific estramustine-binding protein (EMBP) which is present in human glioma tissue. In this study we have examined the effects and pharmacokinetics of EaM in the nitrosourea induced BT4C rat glioma model. The tumor was characterized by infiltrative growth with a histopathological picture resembling gliosarcoma. The presence of EMBP was demonstrated by immunohistology. In vitro EMP caused a dose-related inhibition of BT4C-cell growth. In vivo, in the rat model, a significant inhibition of tumor growth was obtained after administration of EaM 20 mg/kg/d i.p. The pharmacokinetics of EaM resembled that found in the human clinical situation with EaM as the main metabolite accumulating in tumor tissue. The mean concentration ratio of EaM was 15.6 in tumor versus serum, and 1.8 in tumor versus normal brain of 1.8. The cytotoxic effect demonstrated in the rat glioma model justifies further evaluation of EMP/EaM in the treatment of malignant gliomas.

Muscle and adipose tissue morphology and metabolism in Cushing's syndrome.

Femoral and abdominal adipose tissue cellularity and metabolism as well as muscle morphology and metabolism were examined in women with Cushing's syndrome and compared with those in nonobese women and obese women with the android and gynoid types of fat distribution. Cushing's syndrome was characterized by abdominal obesity and enlarged abdominal fat cells, with adipose tissue lipoprotein lipase activity elevated 2-3 times that in normal women and low lipolytic capacity. Muscle tissue in women with Cushing's syndrome had a relatively low proportion of type I (30%) and a high proportion of type IIB (32%) muscle fibers, similar to those in android obesity (45% and 25%, respectively) and in contrast to fiber composition in gynoid obesity (55% and 12%, respectively). Glycogen synthase activity in the lateral vastus muscle was very low. We suggest that the enlargement of abdominal fat depots in women with Cushing's syndrome is at least partially due to elevated adipocyte lipoprotein lipase activity and low lipolytic activity. Furthermore, the abnormal muscle fiber composition might be caused by the corticosteroid excess. Such muscle is known to be relatively insulin insensitive and might thus contribute to the marked insulin resistance that occurs during chronic corticosteroid excess.

Traumatic aneurysms of cerebral arteries. A study of five cases.

Five cases of traumatic aneurysms of cerebral arteries are presented, two located at the internal carotid artery, and three at peripheral arterial branches. The manifestation of the aneurysm was a delayed neurological deterioration due to bleeding from the aneurysm, 4-35 days (mean 21 days) after the head trauma; four patients had an intracerebral haematoma and one patient had a subarachnoid haemorrhage. One patient died from extensive cerebral injuries with the aneurysm untreated. In four cases the aneurysm was treated surgically. Three patients returned to their former occupation and one patient died from late septic complications. It is concluded that signs of delayed intracranial bleeding after a head trauma should raise the suspicion of an underlying traumatic aneurysm, and in addition to a CT-scan an angiography should be performed.

External hydrocephalus in infants.

External hydrocephalus means abnormal fluid accumulation in the subarachnoid space under increased pressure with no or slight widening of the ventricles. 9 children were investigated because of pathologically increasing head circumference and abnormal transillumination. PEG and/or CT showed widened sulci frontally, parietally and interhemispherically but no widening of the ventricles. 7 patients were subjected to exploratory craniotomy which disclosed a deep arachnoid space. 2 patients were shunted. All follow-up CT examinations showed normal conditions. We suggest that infants with clinical signs of hydrocephalus and CT picture of external hydrocephalus should not be treated with shunt. The widening of the subarachnoidal space will normalize. The rate of headgrowth will also normalize.

Superior sagittal sinus blood flow in the dog measured by an electromagnetic flow meter. A comparison with a radioactive gas elimination method.

A simple method for continuous measurement of superior sagittal sinus blood flow (SSBF) in dogs, using an electromagnetic flow meter around the intact vessel, is presented. This method is compared with a procedure measuring radioactive gas elimination upon intra-arterial indicator injection. A good correlation between the cerebral blood flow (CBF), calculated from the fast component of the elimination curve and SSBF (r = 0.96) was found within a CBF range of 50-200 ml/100 g min.

Early effects of E. coli endotoxin on superior sagittal sinus blood flow. An experimental study in dogs.

In an earlier study in dogs we found a reduced cerebral blood flow measured intermittently during the first hours after an intravenous injection of E. coli endotoxin. Within 5 min after the endotoxin injection, a temporarily reduced cerebrospinal fluid pressure was seen irrespective of changes in arterial blood pressure. One possible explanation for this could be an early reduction of the blood flow in the brain. To test this hypothesis, the initial flow reaction was evaluated by measurement of the blood flow in the superior sagittal sinus using an electromagnetic probe around the intact sinus. In five animals following E. coli endotoxin 1.0-1.5 mg/kg intravenously, the superior sagittal sinus blood flow decreased within 2 min, followed by increasing flows within 15 min and thereafter continuously decreasing values up to 60 min, thus giving a two-phase vascular reaction. In all animals there was a marked initial increase in cerebrovascular resistance and the fall in blood flow was thus not a mere consequence of blood pressure changes. In three other animals pretreated with methysergide, a serotonin antagonist, no increase in cerebrovascular resistance was seen during the initial phase. Later, the reaction was similar in all eight animals.

Cerebral blood flow, cerebrovascular resistance and cerebral metabolic rate of oxygen in severe arterial hypoxia in dogs.

Cerebral blood flow and cerebral oxygen uptake were studied during severe arterial hypoxia in anesthetized dogs. It was shown that the hypoxic vasodilatation in the brain reaches a limit at an arterial oxygen saturation at about 25% and that this vasodilatation is less than that which may be induced by hypercapnia. A further deepening of the arterial hypoxia at a maintained cerebral perfusion pressure is combined with a continuous decrease in cerebral venous oxygen tension and a reduced oxygen uptake.

Cerebral blood flow, cerebrovascular resistance, cerebral metabolic rate of oxygen and intracranial pressure during and after severe prolonged arterial hypoxia in dogs. The role of dopamine in the deep hypoxic state.

The effect of extreme, prolonged arterial hypoxia on cerebral blood flow, oxygen uptake and intracranial pressure was studied in anesthetized dogs. The experiments were performed along two lines. Both started with a period of hypoxia of about 40 minutes to 2 hours. Thereafter normoxia was restituted in one group and the animals were studied for another 1-2 hours. In the other group with continued hypoxia dopamine was administered. During the hypoxic period the cerebral blood flow decreased mainly as a result of vasoconstriction after an initial marked flow increase. Cerebral oxygen uptake was reduced. Intracranial pressure increased, largely in proportion to blood flow changes, and no indication of important brain edema appeared. In the "recovery" period at normoxia the cerebral oxygen uptake showed an increase during the observation time. The blood flow, initially high, returned to the control level within the observation period. Dopamine infusion during continued hypoxia induced a vasodilatation, with reduction of vascular resistance to the values found at the induction of hypoxia, and with an increase of the cerebral oxygen uptake. An important role of endogenous dopamine in the hypoxic vasodilatation is suggested.

Studies on the influence of monoamines on the cerebrovascular response to arterial hypoxia.

The cerebrovascular response to arterial hypoxia was studied during blockade of the vascular dopamine receptors and during alpha-adrenergic receptor stimulation and blockade in anaesthetized dogs. Dopamine receptor blockade with pimozide or haloperidol invariably decreased the degree of hypoxic vasodilatation in the brain pointing to a functional role of dopamine in this situation. Alpha-receptor blockade did not change the response, while stimulation of these receptors decreased the dilatory response even in deep arterial hypoxia.