The trans-sphenoidal resection of pituitary adenomas in elderly patients and surgical risk.

In western countries, the process of "ageing of the population" is increasingly forcing clinical medicine to find answers for pathologies affecting the elder segments of our community. In this respect, pituitary adenomas often raise difficult questions on surgical indications, since little is known about postoperative morbidity and mortality in elderly patients. The transsphenoidal endonasal approach (TNS), which is considered the gold standard for surgical resection of the majority of functioning and non-functioning pituitary adenomas, is supposed to be a low morbidity and mortality procedure in adult patients. However, only a few contradicting data are available in the literature about elderly patients. In this paper we retrospectively analyze a cohort of 43 consecutive patients aged more than 65 years, operated on for pituitary adenomas at our Institution in the years 1998-2007. These patients were treated by transsphenoidal endonasal approach (TNS) for resection of non-functioning pituitary adenomas (n = 31), GH-secreting adenomas (n = 4) and ACTH-secreting adenomas (n = 8). Clinical records reported a macroadenoma with tumour-related mass symptoms in about 80 % of patients; single or multiple pituitary deficits were present in 44 % of patients. Regarding comorbidities, cardiac disease was the most frequently observed (86 %); assessment of anaesthesiological risk indicated a moderate to severe ASA score in most patients, 11 % showing a 4-5 score. On the basis of current criteria, our retrospective analysis revealed that cure was achieved in 54 % of patients. The outcome was similar to that observed in the general population of patients undergoing transphenoidal surgery in our centre, without differences in the rate of surgical and endocrinological cure, minor and major surgical complications and hospitalization duration. In particular, no significant anaesthesiological complications were observed and no patient developed either permanent diabetes insipidus or cerebrospinal fluid rhinorrhea. In conclusion, in specialized centres the surgical treatment of pituitary adenomas via the transsphenoidal route can be a safe and effective procedure even in elderly patients.

Glucosylceramide synthase protects glioblastoma cells against autophagic and apoptotic death induced by temozolomide and Paclitaxel.

Glioblastoma is a deadly cancer with intrinsic chemoresistance. Understanding this property will aid in therapy. Glucosylceramide synthase (GCS) is associated with resistance and poor outcome; little is known about glioblastomas. In glioblastoma cells, temozolomide and paclitaxel induce ceramide increase, which in turn promotes cytotoxicity. In drug-resistant cells, both drugs are unable to accumulate ceramide, increased expression and activity of GCS is present, and its inhibitors hinder resistance. Resistant cells exhibit cross-resistance, despite differing in marker expression, and cytotoxic mechanism. These findings suggest that GCS protects glioblastoma cells against autophagic and apoptotic death, and contributes to cell survival under chemotherapy.

Predictive value of inferior fronto-occipital fasciculus (IFO) DTI-fiber tracking for determining the extent of resection for surgery of frontal and temporal gliomas preoperatively.

AIM: This work reports the analysis of the relationship between inferior fronto-occipital fasciculus (IFO), neoplastic lesions and surgical resection, in patients operated for gliomas located in the frontal, temporal and insular lobes of the dominant hemisphere. Aim of the study is evaluating the predictive value of inferior fronto-occipital fasciculus DTI-fiber tracking (FT) for determining the extent of resection preoperatively. METHODS: We selected 38 cases affected by lesions located in the frontal, temporal and insular lobes of the dominant hemisphere, which were related to the trajectory of the IFO. For each patient preoperative and postoperative MR images and DTI-FT were loaded into the neuronavigation system and merged; volumetric scan analysis was used for establishing tumor location and topography, as well as the volume of the lesion and of the residual tumor. All preoperative fiber tracking datasets were evaluated and the position of the tract (IFO) compared to the tumor was recorded. Postoperative MR scans were then compared with DTI-FT, in order to evaluate the correspondence between the resection boundaries and the trajectory of the fiber tract. RESULTS: Amongst the cases in which the IFO was inside the lesion, we found only incomplete resections (5 subtotal and 6 partial resections), while considering the cases in which the IFO was located outside the tumor, it was possible to perform a relevant (total/subtotal) resection in 18 of them (78%). CONCLUSION: FT of the inferior frontal-occipital fasciculus predicts the possibility and the extent of the resection for a frontal, temporal and/or insular lesion of the dominant hemisphere.

Microsurgical endoscopic-assisted retrosigmoid intradural suprameatal approach: anatomical considerations.

AIM: The aim of this study was to evaluate the feasibility of microscopic endoscopic assisted suprameatal tubercle drilling with a retrosigmoid approach and it focuses on the anatomic structures identified with the endoscope. The advantages of the 30 degrees optic view are also described. METHODS: Fifty dry temporal bones were studied in order to estimate the variability of the prominence of the suprameatal tubercle. Eight fresh cadaveric specimens were prepared for a retrosigmoid approach to allow for microscopic endoscopic assisted suprameatal tubercle drilling. The increase in trigeminal exposure and neurovascular structures visualization with the endoscope, using 0 degrees and 30 degrees optics were then evaluated. RESULTS: Three major types of the suprameatal tubercle were found: 1) a large size tubercle (> 6 mm, 9/50 cases); 2) a medium size tubercle (3-6 mm, 37/50 cases); and 3) an almost absent suprameatal tubercle (< 3 mm, 4/50 cases). Microscopic endoscopic assisted suprameatal tubercle drilling with opening of the Meckel's Cave was found to be technically feasible in all cases. The increase in trigeminal nerve exposition was of 9 mm on average. Endoscopic exploration with 0 degrees and 30 degrees optics made possible the identification of all neurovascular structures in the area. CONCLUSION: Microscopic endoscopic assisted suprameatal tubercle drilling is a feasible procedure that allows the identification of all neurovascular structures in the cerebellopontine angle and petrous apex region. The opening of Meckel's Cave may be particularly useful for lesions located in the cerebellopontine angle having a minor component that extends anteriorly and laterally in the middle cranial fossa.

Present day's standards in microsurgery of low-grade gliomas.

Low-grade gliomas are slow growing intrinsic lesions that induces a progressive functional reshaping of the brain. Surgical removal of these lesions requires the combined efforts of a multidiscipinary team of neurosurgeon, neuroradiologist, neuropsychologist, neurophysiologist, and neurooncologists that all together contribute in the definition of the location, extension, and extent of functional involvement that a specific lesion has induced in a particular patient. Each tumor has induced particular and specific changes of the functional network, that varies among patients. This requires that each treatment plan should be tailored to the tumor and to the patient. When this is reached, surgery should be accomplished according to functional and anatomical boundaries, and has to aim to the maximal resection with the maximal patient functional preservation. This can be reached at the time of the initial surgery, depending on the functional organization of the brain, or may require additional surgeries, eventually intermingled with adjuvant treatments. The use of so called brain mapping techniques extend surgical indications, improve extent of resection with greater oncological impact, minimization of morbidity and increase in quality of life. To achieve the goal of a satisfactory tumor resection associated with the full preservation of the patients abilities, a series of neuropsychological, neurophysiological, neuroradiological and intraoperative investigations have to be performed. In this chapter, we will describe the rationale, the indications and the modality for performing a safe and rewarding surgical removal of low-grade gliomas by using these techniques, as well as the functional and oncological results.

Bilateral intracavernous carotid artery aneurysms presenting as abducens nerve palsy: case report.

Bilateral intracavernous carotid artery aneurysms are very rare and can be usually observed in patients with multiple intracranial aneurysms. Here we present the case of a 73 year-old woman who experienced worsening diplopia due to progressive bilateral paresis of the lateral rectus muscles. Computed tomography (CT) and magnetic resonance imaging (MRI) examinations showed bilateral roundish parasellar and intracavernous masses, with homogeneous contrast-enhancement and absence of subarachnoid haemorrhage (SAH). Cerebral angiography revealed bilateral aneurysms of the intracavernous carotid artery. Once considered the age of the patient, the anatomical features of the aneurysms and the risks of traditional or endovascular surgery, we decided not to proceed to any treatment other than the orthoptic correction of the diplopia and the careful correction of arterial hypertension. We provide a brief review of the literature on bilateral intracavernous aneurysms and a discussion about their treatment.

A potential catastrophic trap: an unusually presenting sellar lesion.

A 63-year-old man was admitted to our emergency unit complaining headache, vomit and vertigo. A MR of the brain showed an expanding lesion within the sellar region. A subsequent angio-MR excluded any intracranial vascular malformations. Surprisingly, a cerebral angiography performed later on the basis of worsening of neurological signs and symptoms, demonstrated an aneurysm of the internal carotid artery. At the best of our knowledge, this is the first case of a thrombosis of an intracavernous carotid aneurysm mimicking a pituitary apoplexy documented by MR and angio-MR. The treatment of a milder syndrome of pituitary apoplexy is still controversial. This case would favour conservative treatment opposed to surgery at least when an intracavernous extension or invasion of the adenoma would limit the opportunity of a complete tumour removal.

Autologous transplantation of muscle-derived CD133+ stem cells in Duchenne muscle patients.

Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive muscle disease due to defect on the gene encoding dystrophin. The lack of a functional dystrophin in muscles results in the fragility of the muscle fiber membrane with progressive muscle weakness and premature death. There is no cure for DMD and current treatment options focus primarily on respiratory assistance, comfort care, and delaying the loss of ambulation. Recent works support the idea that stem cells can contribute to muscle repair as well as to replenishment of the satellite cell pool. Here we tested the safety of autologous transplantation of muscle-derived CD133+ cells in eight boys with Duchenne muscular dystrophy in a 7-month, double-blind phase I clinical trial. Stem cell safety was tested by measuring muscle strength and evaluating muscle structures with MRI and histological analysis. Timed cardiac and pulmonary function tests were secondary outcome measures. No local or systemic side effects were observed in all treated DMD patients. Treated patients had an increased ratio of capillary per muscle fibers with a switch from slow to fast myosin-positive myofibers.

Endoscopic treatment of colloid cysts of the third ventricle: long-term results in a series of 6 consecutive cases.

AIM: Colloid cysts of the third ventricle represent 0.5-2% of all intracranial tumors. Several surgical approaches have been proposed for the treatment of these lesions and endoscopy is the most recent one, but the best treatment still remains controversial. We decided to treat colloid cysts with endoscopic approach since 1999. In this paper we present our results in 6 consecutive cases admitted at our institution from 1999 to 2004. METHODS: There were 4 males and 2 females. The mean age was 51.6 (range 29-77). All the cysts were symptomatic. The presenting symptom was headache in 4 patients, gait disturbance in 2, altered vision in 2, mental status change in 2, urinary incontinence in 2, loss of consciousness in 2 and short-term memory loss in 1 patient. All the endoscopic procedures were performed via a right precoronal burr hole, with a rigid endoscope. RESULTS: The removal was radiologically complete in 4 cases and incomplete in 2. Overall outcome was good in all cases, with an improvement of colloid cyst-related hydrocephalus in all the patients. There was no surgical mortality. The mean follow-up period was 52.5 months. No tumor recurrences were observed. Complications occurred in only one patient: a septic ventriculitis, venous thrombosis of the right leg and pulmonary embolism developed, but completely resolved during the hospitalization time. CONCLUSION: The endoscopic approach for the removal of colloid cysts of the third ventricle represents a safe procedure, and can be considered a very good option for the treatment of these lesions.

237 ACoA aneurysms clipped or embolized. Outcomes measurement using the De Santis-CESE assessment tool.

AIM: The aim of this retrospective study was to demonstrate the difference in patient outcomes after treatment for bleeding endocranial aneurysms when evaluated with methods based on different assessment criteria. METHODS: The outcome of 237 patients, 141 of which were operated on for anterior communicating artery aneurysm and 96 embolized, was assessed by a new method developed by De Santis. The patients operated on were assessed by the Glasgow Outcome Scale (GOS) and Rank Disability Scale (RDS) and the results of the latter were compared with the new method, the De Santis-CESE (Clinical Emotional Social Evaluation) method, which consists of a clinical evaluation and a numeric scoring system based on seven standard points. Comparison between the three methods showed significantly different outcomes. Patients who underwent surgical operation showed changes in character and behaviour, whereas the others showed cognitive, emotional and sexual habit changes. CONCLUSION: Compared with the GOS and RDS instruments, the CESE method showed significant differences in patient outcome assessment, particularly regarding best outcomes. These differences may be due to the greater sensitivity of the CESE method over the other two scales. Furthermore, surgical patients seemed to achieve a better outcome than endovascular patients. The authors intend to conduct a prospective study to test the results obtained in this retrospective study.

Cortical and subcortical motor mapping in rolandic and perirolandic glioma surgery: impact on postoperative morbidity and extent of resection.

AIM: Surgery for gliomas located inside or in proximity of motor cortex or tracts requires cortical and subcortical mapping to locate motor function; direct electrical stimulation of brain cortex or subcortical pathways allows identification and preservation of motor function. In this study we evaluated the effect which subcortical motor mapping had on postoperative morbidity and extent of resection in a series of patients with gliomas involving motor areas or pathways. METHODS: One hundred and forty-six patients were included in the study. Intraoperative findings of primary motor cortex or subcortical tracts were reported, together with incidence of new postoperative deficits at short (1 week) and long term (1 month) examination. The relationship between intraoperative identification of subcortical motor tracts and extent of resection was reported. RESULTS: The motor strip was found in 133 patients (91%) and subcortical motor tracts in 91 patients (62.3%). New immediate postoperative motor deficits were documented in 59.3% of patients in whom a subcortical motor tract was identified intra-operatively and in 10.9% of those in whom subcortical tracts were not observed; permanent deficits were observed in 6.5% and 3.5%, respectively. A total resection was achieved in 94.4% of patients with high-grade gliomas and in 46.1% of those with low-grade gliomas.

Review of language organisation in bilingual patients: what can we learn from direct brain mapping?

Although the majority of people worldwide are bilingual, the brain representation of language in bilingual persons is still a matter of debate. Since the beginning of the studies conducted on bilinguals, most authors denied that learning a new language requires a new semantic processing or the involvement of new cortical areas. In this paper, we review neurosurgical studies using direct electrocortical or subcortical stimulation techniques for brain mapping in bilingual subjects and compare this data with that obtained from other brain mapping methods. The authors focused on the most controversial issue whether multiple languages are represented in common or distinct cerebral areas. Seven direct brain mapping studies from different teams focused on bilingualism and multilingualism. All these studies showed that even if cerebral representation of language in multilingual patients could be grossly located in the same cortical region, it was possible to individualise distinct language-specific areas by direct cortical stimulation in the dominant frontal and temporo-parietal regions. Task- and language-specific sites were also described, demonstrating an important specialisation of some cortical areas. Using subcortical stimulation, some authors were able to find specific white matter tracts for different languages. Finally, all authors recommend in bilingual patients who need brain mapping for neurosurgical purpose to test all languages in which the subjects are fluent.

Clinical correlates and cognitive underpinnings of verbal fluency impairment after chronic subthalamic stimulation in Parkinson's disease.

A decline in verbal fluency is the most consistent neuropsychological sequela of deep brain stimulation (DBS) for Parkinson's disease. We assessed clinical correlates and switching and clustering subcomponents in 26 parkinsonians undergoing subthalamic DBS. Post-surgical motor improvement was accompanied by worsening at both letter and category fluency tasks. Total number of words and switches decreased, while average cluster size was unchanged. Worsening tended to be prominent in patients with baseline poorer cognitive status and more depressed mood. Impairment of shifting suggests prefrontal dysfunction, possibly due to disruption of fronto-striatal circuits along the surgical trajectory and/or to high frequency stimulation itself.

Characterization of the gamma-aminobutyric acid receptor system in human brain gliomas.

The properties of [3H]-gamma-aminobutyric acid [( 3H]GABA) binding were studied in biopsied specimens from normal human brain and from 18 cases of human brain gliomas, made up of 6 astrocytomas, 6 glioblastomas, 3 oligodendrogliomas, and 3 medulloblastomas. In fresh membranes obtained from normal gray and white matter one population of Na+-dependent GABA receptors was observed, while in the frozen Triton X-100-treated membranes two distinct populations of Na+-independent binding sites were detected. Specific GABA binding sites in brain gliomas were shown only in frozen Triton X-100-treated membranes. As in normal tissue, these receptors are Na+-independent and bind [3H]GABA with two distinct affinity components. The biochemical profiles of [3H]GABA binding to membranes obtained from different tumors of glial origin are quite similar and cannot be related to the degree of malignancy of the neoplasia.

Ganglioside pattern of normal human brain, from samples obtained at surgery. A study especially referred to alkali labile species.

The ganglioside pattern from normal human temporal cortex and cerebellum has been studied in fresh specimens obtained at surgery. The analyses have been performed by two-dimensional thin layer chromatography with an intermediate ammonia treatment which is a methodology particularly suitable for resolving alkali labile gangliosides. Alkali labile gangliosides were detected in all the analyzed specimens and their content contributed to 23% and 11% of total lipid bound sialic acid, in temporal cortex and cerebellum, respectively.

Characteristics of the cyclic AMP-phosphodiesterase activator in human brain tumours.

The levels of the cyclic adenosine 3',5'-monophosphate (cyclic AMP)-phosphodiesterase (PDE) and the biochemical properties of its endogenous protein activator (PDEA) obtained from the human brain cortex and from different types of human cerebral tumours have been evaluated. The effects of the various PDEAs were studied measuring the activation of an activator-depleted cyclic AMP-PDE prepared from a normal brain cortex. The PDEA, obtained from normal and pathological tissues, did not change the affinity of the purified PDE for cyclic AMP, while it increased the Vmax of the enzyme. On the other hand, a cross-activation study showed that the PDEA lacked tissue specificity and was present in the tissue in excess over the enzyme. The levels of cyclic AMP-PDE and PDEA were much higher in normal than in tumoural tissues. The enzyme activity decreased in cerebral tumours more markedly than the protein activator. This biochemical pattern was more evident in the tumours of glial origin which are the most malignant.

Calmodulin content in human brain tumors.

Using a radioimmunoassay method, the particulate and soluble calmodulin levels were determined in biopsied specimens from normal human brain and from various human brain tumors. Both in normal and pathological tissues the major portion of calmodulin was revealed in the cytosol. The chromatographic elution profiles of calmodulin obtained from soluble and particulate fractions of the same specimen were identical, thus suggesting an identity of the supernatant and particulate form of calmodulin. In all the examined oncotypes, the calmodulin content was lower than in normal extracts and this biochemical feature could not have been correlated with the degree of malignancy of the neoplasia. Furthermore, the translocation of calmodulin from the particles to the cytoplasm, reported in other rapidly growing tumors, lacks in human cerebral ones. Our findings indicate that in human brain oncotypes the calmodulin distribution is quite different from that found in tumors taken from other tissues, where its level is increased and a positive correlation between calmodulin concentration and growth rate of neoplastic tissue has been revealed.

The value of brain scanning in the diagnosis of recurrences of brain tumours.

The Authors consider critically the possibilities of brain scanning in the diagnosis of recurrences of brain tumours. They examine a series of 143 cases subjected in 180 brain scans exams. The accuracy of the diagnosis is demonstrated by operative controls and verified by the results of the Common neuroradiologic investigations (angiography and air study). The analysis of patients according to the different types of tumours, enabled us to make the following conclusions: 1) Percentages of positivity of recurrences with astrocytomas and localisations in the posterior fossa are highest than that obtainable with the primitive tumour. 2) Flap activity is not considered as a limitative factor of the diagnostic possibilities of recurrence, except in meningiomas of small dimensions, near the longitudinal sinus. 3) In our series, there is only a false negative, surgically verified, and diagnosis of negativity is confirmed by the percentages of accordance with neuroradiogical methods. 4) Pneumoencephalography is more valuable than arteriography in the diagnosis of recurrence, but only the association of the two methods provides percentages of exact diagnosis comparable to the results of brain scanning. 5) Brain scanning gave false positive results only in cases of radionecrosis.

The dysraphic state of the posterior fossa. Clinical review of the Dandy-Walker syndrome and the so-called arachnoid cysts.

The Authors report their case material concerning some basic items of the dysraphic pathology of the Posterior Fossa: 22 cases of Dandy Walker syndromes (DWS) and "Arachnoid Cysts" (PFC). The mean clinical findings (predominant involvement of the vestibular structures of the brain stem in the DWS, frequent epileptic seizures and some cases of hypothalamic disturbances in the PFC) are discussed in the light of current embryological theories on Weed's "area membranacea". Finally the results of differential surgical treatments are examined: good or satisfactory results were obtained with shunts, while still debatable seems to be the direct surgical approach.

Pressure volume relation in patients with subarachnoid haemorrhage and diffuse cerebral vasospasm.

Seven patients, presenting severe neurological status (grades IV and V according to Hunt and Hess) and cerebral vasospasm following subarachnoid haemorrhage were submitted to continuous ICP recording the study of the cerebral elastic properties by PVI compliance computation. All the patients presented low ICP values (below 20 mmHg) for the whole period of monitoring. The results of PVI and compliance measurements show that the pressure-volume curves in these patients are different from the physiological P-V curve. The PVI values progressively increase with the rise in ICP. The significance of this finding is discussed.