Adenosine-induced cardiac arrest in complex cerebral aneurysms surgery: an Italian single-center experience.

AIM: Even if endovascular techniques are improving, treatment of complex intracranial aneurysms still remains a neurosurgeon challenge. Adenosine administration, producing a brief and profound systemic hypotension, seems to improve surgical aneurysm visualization facilitating its exclusion with less risks of rupture. In our retrospective study we confirmed that adenosine advantages could be determinant for an optimal surgical result. METHODS: We retrospectively reviewed all unruptured complex cerebral aneurysms surgically treated in our institution between August 2009 and April 2012. Treatment of those aneurysms was surgical, with proximal temporary artery occlusion or adenosine induced flow arrest. We compared the two different techniques, evaluating intra- and postoperative data; a three-month follow-up including a neurological assessment, cerebral angiography and echocardiography for the adenosine group was performed. RESULTS: Twenty-four patients were collected in our study. Eleven patients underwent traditional temporary proximal clipping while in 13 patients intraoperative adenosine was used. Most common location was paraclinoid region. We did not observe any complication in the adenosine group. Adenosine was well tolerated, spontaneous recovery of sinusal cardiac rhythm was observed even at high and subsequent doses. The Intensive Care Unit and Hospital length of stay were shorter in adenosine group. A three-month follow-up did not show cardiac abnormalities with good angiographic aneurysms exclusion. CONCLUSION: We observed that adenosine administration allowed an easier clipping thanks to a reduced wall tension in a clearer surgical field without cardiological adverse events. In our opinion adenosine induced arrest technique could be an efficacious, harmless and reliable alternative strategy for surgical treatment of complex cerebral aneurysms.

Neurophysiological assessment of the injured spinal cord: an intraoperative approach.

STUDY DESIGN: Prospective, observational study. OBJECTIVES: To assess the spinal cord function intraoperatively in subjects during spine stabilization for spinal cord trauma, by recording muscular (m-MEPs) and epidural motor evoked potentials (e-MEPs, D wave) along with cortical and epidural somatosensory evoked potentials (e-SEPs) and predicting the outcome of spinal cord injury (SCI). SETTING: Regional Trauma Center, Torino, Italy. METHODS: Fifty-five patients were intraoperatively studied during posterior spine stabilization surgery for traumatic SCI. In all, 21 of these had complete SCI, 14 an incomplete SCI-6 of them with central cord syndrome and 1 with central cord plus Brown Sequard syndrome-and 20 patients were neurologically uncompromised. RESULTS: The neurophysiologic profile of the complete SCI was the absence of both m-MEPs and e-MEPs caudally to the lesion site, associated with a lack of cortical and e-SEPs cranially to the lesion site. None of these patients recovered motor function in the follow-up. A clearly detectable caudal D wave was associated with motor recovery even in deeply paraparetic patients. In one neurologically incomplete patient a reversible deterioration of m-MEPs and e-MEPs was observed during the compression-distraction manoeuvre. CONCLUSION: Intraoperative neurophysiological evaluation of SCI patients can provide information about spinal cord function that is not retrievable by other clinical means and can correctly predict neurological outcome. Intraoperative testing during early stabilization of the spine of deeply paraparetic SCI patients provides additional information about their neurological profile.

Effects of octreotide treatment on the proliferation and apoptotic index of GH-secreting pituitary adenomas.

To investigate the effects of octreotide administration on the growth rate of GH-secreting pituitary adenomas, we measured both the Ki-67 labeling index (LI) and the apoptotic index in tumor specimens from octreotide-treated or matched untreated acromegalic patients. Thirty-nine patients who received octreotide until the day of or the day before surgery and 39 untreated patients matched for sex, age, tumor size, extension, and invasiveness were studied. Immunocytochemical analysis was performed on paraffin-embedded material using a monoclonal antibody (MIB-1) directed against a proliferation-associated nuclear antigen, Ki-67, to measure the growth fraction. Apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick endlabeling method, using a monoclonal antibody recognizing areas of DNA fragmentation. The Ki-67 LI and apoptosis were counted on separate slides in at least 1000 evaluable cells. Octreotide-treated patients showed a lower Ki-67 LI (1.8 +/- 0.3%) than untreated controls (3.8 +/- 0.7%; P < 0.02). Overall, the mean Ki-67 LI of treated patients was 53% lower than that in untreated patients. The antiproliferative effect of octreotide occurred independently of tumor extension and invasiveness. Octreotide-treated and untreated patients showed similar apoptotic indexes (0.6 +/- 0.2% and 0.8 +/- 0.3%, respectively). There was a positive correlation between the Ki-67 LI and the apoptotic index (r = 0.29; P < 0.03). Our study demonstrates that acromegalic patients receiving chronic octreotide treatment have a lower value of the proliferation marker Ki-67, but no significant difference in the apoptotic index compared with matched untreated patients. The antiproliferative effect of octreotide on GH-secreting adenomas should imply a lower risk of tumor growth during long-term chronic treatment with the drug.

Prolactin receptors in human meningiomas: characterization and biological role.

Sixty cerebral meningioma specimens obtained at surgery from 34 female and 26 male patients were examined for the presence of prolactin (PRL) receptors. These were compared with normal arachnoid tissue from which these tumours arise. PRL receptors were detected in 61.7% of meningiomas whereas no PRL binding was found in samples of normal arachnoid tissue. No relationship was found when sex or histological findings were compared with the presence of PRL receptors. Receptor-positive tumours had saturable and high-affinity (Kd, 4.8 +/- 0.5 ng/ml) receptors with hormonal specificity for human PRL (hPRL) resembling that of other target tissues of PRL in man. The biological role of these receptors was investigated in primary cell cultures derived from meningioma tissue characterized for PRL receptor. When human PRL was added to the culture medium, in doses ranging from 1 to 200 ng/ml, a dose-dependent stimulation of 3H-thymidine incorporation was observed only in PRL-receptor positive tumours. The PRL concentrations required to produce a half-maximal effect ranged from 11 to 20 ng/ml and were quite close to the dissociation constant (Kd) of binding of PRL to its receptors. PRL also caused an increase of cell number compared with control with a significant effect after 3 and 4 days of culture. In conclusion, these findings indicate that a large number of human meningiomas express specific and functional receptors for PRL which are involved in mediating its proliferative effects.

Spasmodic torticollis due to neurovascular compression of the 11th nerve. Case report.

An unusual case of spasmodic torticollis caused by posteroinferior cerebellar artery compression of the spinal accessory nerve is reported. The spasmodic torticollis was cured by abolishing the neurovascular compression.

Microvascular changes in progressive systemic sclerosis: immunohistochemical and ultrastructural study.

Fifteen patients affected by Progressive Systemic Sclerosis have been studied. With immunofluorescence, specific antibodies against collagen type IV and laminin clearly outlined the microvessels, while endothelial cells showed a brilliant heavy fluorescence for vimentin antibodies. In the deep dermis, fibronectin proved to have increased. At electron microscopy, microvessels appeared with occluded lumina due to the presence of swollen endothelial cells. Endothelial cytoplasm was filled with intermediate filaments (vimentin type), generally condensed into peripherally located bundles or in perinuclear rings. The perivascular basal lamina was thickened and laminated. Although these changes do not demonstrate a specific pattern, representing a common step in several connective tissue disorders, the data tend to confirm a clear involvement of the microvasculature in Progressive Systemic Sclerosis.

The measurement of pain threshold in man by means of electrical stimuli. A critical appraisal.

The problem of pain threshold measurement in man is critically considered. The advantages of electrical stimuli in determining the cutaneous pain threshold are discussed. The conducting properties of the skin to electric current are carefully examined: in fact, such properties must be taken into account when electrical stimuli are applied to the skin. A series of investigations on pain threshold measurement by means of electrical stimuli are reported. The different sensations induced by stimulating the skin with different kinds of electrodes and different types of stimuli were analysed: trains of 5 square waves of 0.5-2 msec at the frequency of 250 Hz, applied to the skin by means of unpolarizable electrodes, were selected as the best suited stimuli for practical application. This kind of stimulation was applied in physiological and clinical investigations. The measurement of pain threshold by electrical stimuli was especially useful for the clinical examination and for the study of pathogenetic mechanisms of painful diseases.

Hyperprolactinaemia and prolactin binding in benign intracranial tumours.

BACKGROUND: Meningiomas have been found to have receptors for several hormones, such as oestrogen, progesterone, somatostatin, dopamine and recently also for prolactin. METHODS: To investigate any possible role of prolactin in the growth of those tumours we detected the presence of prolactin-receptors (PRL-R) in 22 meningiomas and we correlated these data with PRL serum levels in patients before surgery. We also studied 13 patients with schwannomas and 7 with other cerebral tumours (4 glioblastomas, 2 ependymomas and 1 astrocytoma). RESULTS: Increased prolactin binding was present in 10 (45.4 percent;) meningiomas, 9 (69.2 percent;) schwannomas and in the patient with astrocytoma. The presence of high PRL levels was present in 6 (27.2 percent;) patients with meningiomas, 8 (61.5 percent;) with schwannomas and in 3 (42.8 percent;) with other tumours. No direct correlation was present between serum PRL levels and PRL binding in all groups. CONCLUSIONS: In conclusion we confirmed the presence of PRL receptors in patients with meningiomas and we have also shown the presence of PRL receptors also in schwannomas. Moreover increased serum PRL were shown in some patients with different tumours of nervous tissue before surgery. Our data could suggest that PRL might have a role in the growth of meningiomas and schwannomas.

Clinical and neuroimaging features of severely brain-injured patients treated in a neurosurgical unit compared with patients treated in peripheral non-neurosurgical hospitals.

Most European TBI patients are managed in peripheral hospitals without benefit of guidelines for transfer of such patients to neurosurgical units as needed. This report compares clinical features and outcomes in two series of severe TBI patients: those admitted to a neurosurgical centre or to a general hospital, all in the Piedmont Region of Italy. Of 630 patients with a GCS of 3-8, 351 were admitted to a centralized neurosurgical unit, and 279 were admitted and treated at a peripheral hospital. All patients had a CT scan read by a neurosurgeon on duty and were classified using the Marshall criteria as having a diffuse injury or non-surgical mass lesions. Outcomes were assessed between 6 months and 6 years using either the GOS Extended or the GOS. Independent variables were age, sex, GCS score and Marshall classification. All the examined factors were significantly different between the two groups (p<0.001). For patients admitted to the neurosurgical centre, age, Marshall classification of the CT and GCS were predictors of a favourable outcome, while for patients treated in general hospitals, Marshall classification of the CT, gender and age were predictors of a favourable outcome. Patients admitted to neurosurgical centres are different from those treated in general hospitals not having these specialized facilities and personnel. The absence of guidelines for the transfer of these patients for more advanced care are lacking and should be the focus of new studies on patient referral.

Acute traumatic central cord syndrome.

First described by Schneider in 1954, the syndrome of acute central cervical spinal cord injury is characterized by disproportionately greater motor impairment in the upper compared to the lower extremities, bladder dysfunction and a variable degree of sensory loss below the level of injury. The syndrome has a good prognosis for neurologic and functional recovery. Spontaneous improvement of function is typical. Ten cases are reported. Clinical features, diagnosis and management are discussed.

Intracisternal schwannoma of the spinal accessory nerve presenting as a normal pressure hydrocephalus syndrome. Case report and review of the literature.

Schwannomas of the spinal accessory nerve are rare lesions. They can be characterized by their locations as either intrajugular or intracisternal schwannomas, most of them being intrajugular. Only five cases arising in the cisterna magna are reported in literature. Clinical symptoms generally consist of 11th cranial nerve palsy associated with cerebellar signs and myelopathy. An additional case, studied by MRI, is described. The patient showed a mild cerebellar syndrome and normal pressure hydrocephalus symptoms. He was operated on and the mass completely removed with good postoperative results. The role of MRI for diagnosis of lower cranial nerve schwannomas is stressed, even though does not detect the exact nerve of origin. Total removal of these lesions is recommended, since their benign nature and unavoidable recurrence in case of partial excision.

One hundred and twenty-seven cases of acute subdural haematoma operated on. Correlation between CT scan findings and outcome.

Traumatic acute subdural haematoma is one of the most lethal of all head injuries: the mortality rate is reported to be between 50 and 90%. We reviewed the clinical records of 1688 head injured patients admitted to the Department of Neurosurgery at C.T.O. hospital between 1982 and 1992. In 127 cases (7,5%) CTscan on admission showed acute subdural haematoma requiring surgery because the midline shift was greater than 5 mm. The overall mortality rate was 57% and 23% had functional recovery. The following variables were assessed with regard to morbidity and mortality: mechanism of injury, age, neurological presentation, time delay from injury to intervention, CTscan finding on admission. GCS and CTscan findings were found to be the most important prognostic variable. Timing of operative intervention for clot removal with regard to outcome was not statistically significant. But no conclusions regarding the importance of early haematoma evacuation can be drawn from such an oversimplifying statement, because it does not take into account factors like rapidity of haematoma development and related brain decompensation as well as additional direct brain lesions. The results of this study suggest that the extent of primary brain injury underlying the subdural haematoma is the most important factor affecting outcome.

[Thrombosis of the right internal jugular vein caused by a catheter in the subclavian vein. A complication precluding the insertion of a ventriculo-atrial cerebrospinal fluid shunt]. / Trombosi della vena giugulare interna destra da catetere in succlavia. Una complicanza che ha precluso l'inserzione di derivazione liquorale ventricolo-atriale.

The Authors describe a case of right internal jugular vein thrombosis caused by a catheter in the subclavian vein which occurred in a four-month-old baby with chronic subdural hematomas. They emphasize that this thrombotic complication precludes the insertion of a ventriculo-cardiac shunt and point out the opportunity to prefer left subclavian cannulation in those patients who probably will need a ventriculo-cardiac shunt.

Dumbbell-shaped spinal epidural cavernous angioma. Case report.

Cavernous angiomas are common lesions of the CNS characterized by abnormally dilated blood vessels lined by a thin endothelium, closely clustered together and not separated by normal neural tissue. They are more frequently found intracranially. In the spine, a common location is the vertebral bodies. Intradural extramedullary and intramedullary cavernous angiomas are less frequent lesions, while purely epidural locations are uncommon. Spinal dumbbell-shaped epidural cavernous angiomas are exceedingly rare, and only six cases have been reported in the literature. We describe one additional case whose MRI appearance was indistinguishable from that of a neurinoma, which is a much more common lesion. Surgical treatment is advised and complete radiological evaluation is necessary to rule out concomitant localizations in other organs.

Deep brain stimulation of the subthalamic nucleus: anatomical, neurophysiological, and outcome correlations with the effects of stimulation.

OBJECTIVES: Bilateral chronic high frequency stimulation of the subthalamic nucleus (STN), through the stereotactical placement of stimulating electrodes, effectively improves the motor symptoms of severe Parkinson's disease. Intraoperative neurophysiological and clinical monitoring techniques (neuronal electrical activity recording and intraoperative stimulation) may improve and refine the localisation of the nucleus. The objective of this work was to compare the preoperative CT and MRI localisation with the intraoperative neurophysiological identification of STN. The relation between the localisation of the STN and the position of the most effective contact of the permanent quadripolar electrode at a 3 month and 1 year follow up was also studied. METHODS: Fourteen consecutive parkinsonian patients were submitted to bilateral implant for STN stimulation. All the patients underwent a standard MRI and stereotactic CT to obtain, by image fusion and localisation software, the stereotactical coordinates of STN. The STN extension and boundaries were identified by a semimicrorecording of the neuronal electrical activity. The definitive quadripolar electrode was positioned to locate at least two contacts within the STN recording area. Intraoperative macrostimulation was performed to confirm the correct position of the electrode. Postoperative clinical evaluation of the effects of stimulation was checked for each contact of the quadripolar electrode testing the improvement on contralateral rigidity to select the best contact. This evaluation was repeated at 3 months and 1 year after surgery. RESULTS: In 35.7% of the procedures it was necessary to perform more than one track to get a recording of neuronal activity consistent with STN. The mean position of the central point of all the 28 STN recording areas in respect of the AC-PC line midpoint was 2.7 mm posterior (SD 0.7), 3.8 mm inferior (SD 1.1), and 11.6 mm lateral (SD 0.9), and the mean distance between the anatomical target and the central point of the STN as defined by intraoperative recording was 0.5 mm (SD 0.5) on the anteroposterior plane, 0.7 mm (SD 0.7) on the lateral plane, and 0.9 mm (SD 0.6) on the vertical plane. At 1 year the mean position of the central point of the most effective contact of the electrode in respect of the AC-PC line midpoint was 1.7 mm posterior (SD 0.9), 1.7 mm inferior (SD 1.5), and 12.3 mm lateral (SD 0.9). CONCLUSION: The results highlight the role of the intraoperative recording to get a more accurate localisation of the STN in surgery for Parkinson's disease, allowing the identification of the boundaries and of the extension of the nucleus. The most effective contact of the quadripolar electrode was always in the upper part of the STN recording area or immediately above it, suggesting a role of this region in the clinical effectiveness of the STN electrical stimulation.

Deep brain stimulation of the subthalamic nucleus in Parkinson's disease: effects of variation in stimulation parameters.

OBJECTIVE: To investigate the relation between the variation of the parameters of stimulation and the clinical effectiveness in parkinsonian patients treated with deep brain stimulation of the subthalamic nucleus (STN), to provide information on the electrical parameter setting and the mechanism of action of deep brain stimulation. METHODS: Ten patients with Parkinson's disease bilaterally implanted in the STN were studied. For every patient the intensity of the stimulus necessary to obtain the disappearance of contralateral wrist rigidity (required clinical effect, RCE) and the side effect threshold in 20 different conditions of stimulation, coupling four pulse width values (60, 120, 210, 450 micros) with five rate values (10, 50, 90, 130, 170 Hz) were determined. All the patients were tested after a 12 hour withdrawal of antiparkinsonian drugs, and the clinical evaluation was double blind. RESULTS: In all the patients it was impossible to obtain the RCE using 10 and 50 Hz stimulus rates. For all the other stimulus rate values, the intensity-pulse width curves (IPWCs) for the RCE and for the side effect threshold showed a hyperbolic trend. For every pulse width value, increasing the rate from 90 to 130 and to 170 Hz progressively decreased the intensity of the stimulus necessary to reach the RCE, but the differences were not significant. Within the same rate value, the progressive reduction of the stimulus intensity necessary to obtain the RCE, obtained with the lengthening of the pulse width was significant (p<0.05) only comparing 60 with 210 micros and 60 with 450 micros. CONCLUSIONS: The findings give some useful indications for the electrical parameter setting in deep brain stimulation of the STN, and some information about the mechanism of action of deep brain stimulation.

Asymptomatic extradural haematomas. Results of a multicenter study of 158 cases in minor head injury.

The authors report a study conducted in three Italian neurosurgical centres on 158 patients admitted after a minor head injury and with CT findings of a hitherto asymptomatic significant extradural haematoma. All patients were examined both prospectively by means of a computerized record containing 18 clinical and radiological parameters, and retrospectively by logistical regression analysis, in order to ascertain which factors influenced most the choice of surgical vs. conservative management. The size of the haematoma, rather than its location, and the degree of midline shift were the factors most influential in deciding in favour of surgical treatment, with a specificity of 0.83 and a sensitivity of 0.92. Conservative management of haematomas having a maximum thickness of less than 10 mm with a midline shift of less than 5 mm appears as safe. Outcome was "good recovery" in both the surgical and the nonsurgical patients, with only one death in the whole series, unrelated to the extradural lesion. This study focuses attention on a group of patients who are seldom examined by CT scan, but who can harbour potentially lethal lesions. Extension of CT scan examination to all adult patients with a minor head injury and a skull fracture can be recommended in order to identify significant haematomas in an asymptomatic phase.

Prolactin receptors in human pituitary adenomas.

OBJECTIVE: In the rat, prolactin receptors (PRL-R) have been identified in normal pituitary cells and in anterior pituitary tumours induced by oestradiol. No published data are available concerning PRL-R in the human pituitary. The aim of our study was therefore to detect the presence of PRL-R in the normal human pituitary gland and human pituitary adenomas. DESIGN: Evaluation of free and total PRL-R in the normal pituitary gland and different pituitary tumours characterized by immunocytochemical analysis. PATIENTS: Twenty-six unselected patients (14 M, 12 F) who underwent surgery for pituitary adenoma (3 prolactinomas, 4 GH-PRL adenomas, 5 GH adenomas, 1 ACTH adenoma, 9 glycoprotein and/or alpha-subunit adenomas, 4 null cells adenomas) were studied. Nine pituitaries from subjects whose death was unrelated to brain and endocrine diseases, were also studied as a control group in the PRL binding studies. MEASUREMENTS: Free PRL-R in microsomal membranes were determined by in-vitro radioreceptor assay using 125I-labelled human PRL as ligand. Total PRL-R were also measured in the same membrane fractions by removing endogenous PRL bound to its receptors using 4 M MgCl2. Serum PRL levels were also evaluated in all patients before surgery using an IRMA method. RESULTS: Specific binding values for PRL (free PRL-R) were 0.39 +/- 0.03% (range 0-1.96%) in the pituitary adenomas. These binding values were identical to those observed in normal pituitaries (0.38 +/- 0.07%, range 0.1-0.78%). Elevated PRL binding (1.25% and 1.96%) was found in two patients with PRL secreting adenomas and very high serum PRL levels (5768 and 11240 mU/I. No PRL binding was shown in 4 patients. Treatment of membranes with 4 M MgCl2 increased the specific binding (total PRL-R) in both pituitary tumours (0.5 +/- 0.11%; P < 0.001) and normal pituitaries (0.47 +/- 0.07%; P < 0.02). CONCLUSIONS: Our data have demonstrated the presence of prolactin receptors in normal cadaveric pituitary and in most pituitary adenomas, irrespective of histological classification. In particular, elevated prolactin receptor levels were shown in PRL-secreting tumours from patients with markedly increased serum PRL levels. Our study may support several lines of experimental evidence for a specific functional role for PRL in the growth of some pituitary adenomas.