GLYOXALASE I A111E, PARAOXONASE 1 Q192R AND L55M POLYMORPHISMS IN ITALIAN PATIENTS WITH SPORADIC CEREBRAL CAVERNOUS MALFORMATIONS: A PILOT STUDY.

It is already known that the conditions of increased oxidative stress are associated to a greater susceptibility to vascular malformations including cerebral cavernous malformations (CCMs). These are vascular lesions of the CNS characterized by abnormally enlarged capillary cavities that can occur sporadically or as a familial autosomal dominant condition with incomplete penetrance and variable clinical expression attributable to mutations in three different genes: CCM1(Krit1), CCM2 (MGC4607) and CCM3 (PDCD10). Polymorphisms in the genes encoding for enzymes involved in the antioxidant systems such as glyoxalase I (GLO I) and paraoxonase I (PON I) could influence individual susceptibility to the vascular malformations. A single nucleotide polymorphism was identified in the exon 4 of GLO 1 gene that causes an amino acid substitution of Ala for Glu (Ala111Glu). Two common polymorphisms have been described in the coding region of PON1, which lead to glutamine → arginine substitution at 192 (Q192R) and a leucine → methionine substitution at 55 (L55M). The polymorphisms were characterized in 59 patients without mutations in the CCM genes versus 213 healthy controls by PCR/RFLP methods using DNA from lymphocytes. We found that the frequency of patients carrying the GLO1 A/E genotype among the case group (56%) was four-fold higher than among the controls (14.1%). In the cohort of CCM patients, an increase in the frequency of PON192 Q/R genotype was observed (39% in the CCM group versus 3.7% in the healthy controls). Similarly, an increase was observed in the proportion of individuals with the genotype R/R in the disease group (5%) in respect to the normal healthy cohort (0.5%). Finally, the frequency of the PON55 heterozygotes L/M genotype was 29% in patients with CCMs and 4% in the healthy controls. The same trend was observed in PON55 homozygous M/M genotype frequency (CCMs 20% vs controls 10%). The present study aimed to investigate the possible association of GLO1 A111E, PON1 Q192R and L55M polymorphisms with the risk of CCMs. We found that individuals with the GLO1 A /E genotype, PON192/QR-RR genotypes and PON55/LM-MM genotypes had a significantly higher risk of CCMs compared with the other genotypes. However, because CCM is a heterogeneous disease, other additional factors might be involved in the initiation and progression of CCM disease.

MRI Tractography of Corticospinal Tract and Arcuate Fasciculus in High-Grade Gliomas Performed by Constrained Spherical Deconvolution: Qualitative and Quantitative Analysis.

BACKGROUND AND PURPOSE: MR imaging tractography is increasingly used to perform noninvasive presurgical planning for brain gliomas. Recently, constrained spherical deconvolution tractography was shown to overcome several limitations of commonly used DTI tractography. The purpose of our study was to evaluate WM tract alterations of both the corticospinal tract and arcuate fasciculus in patients with high-grade gliomas, through qualitative and quantitative analysis of probabilistic constrained spherical deconvolution tractography, to perform reliable presurgical planning. MATERIALS AND METHODS: Twenty patients with frontoparietal high-grade gliomas were recruited and evaluated by using a 3T MR imaging scanner with both morphologic and diffusion sequences (60 diffusion directions). We performed probabilistic constrained spherical deconvolution tractography and tract quantification following diffusion tensor parameters: fractional anisotropy; mean diffusivity; linear, planar, and spherical coefficients. RESULTS: In all patients, we obtained tractographic reconstructions of the medial and lateral portions of the corticospinal tract and arcuate fasciculus, both on the glioma-affected and nonaffected sides of the brain. The affected lateral corticospinal tract and the arcuate fasciculus showed decreased fractional anisotropy (z = 2.51, n = 20, P = .006; z = 2.52, n = 20, P = .006) and linear coefficient (z = 2.51, n = 20, P = .006; z = 2.52, n = 20, P = .006) along with increased spherical coefficient (z = -2.51, n = 20, P = .006; z = -2.52, n = 20, P = .006). Mean diffusivity values were increased only in the lateral corticospinal tract (z = -2.53, n = 20, P = .006). CONCLUSIONS: In this study, we demonstrated that probabilistic constrained spherical deconvolution can provide essential qualitative and quantitative information in presurgical planning, which was not otherwise achievable with DTI. These findings can have important implications for the surgical approach and postoperative outcome in patients with glioma.

Necrosis score, surgical time, and transfused blood volume in patients treated with preoperative embolization of intracranial meningiomas. Analysis of a single-centre experience and a review of literature.

PURPOSE: Several authors have demonstrated that preoperative embolization of meningiomas reduces blood loss during surgery. However, preoperative embolization is still under debate. Aim of this study is the retrospective evaluation of necrosis score, surgical time, and transfused blood volume, on patients affected by intracranial meningiomas treated with preoperative embolization before surgery, compared with a control group treated only with surgery. METHOD: Twenty-eight patients with meningiomas were subjected to a preoperative embolization with polyvinyl alcohol (PVA). These patients were divided into two groups: group 1, patients with preoperative embolization performed at least 7 days before surgery; and group 2, patients with preoperative embolization performed less than 7 days before surgery. A statistical evaluation was made by comparing necrosis score, surgical time, and transfused blood volume of these groups. Then, we compared these parameters also with group 3, which included patients with surgically treated meningioma who did not undergo preoperative embolization. RESULTS: Surgery time and transfused blood volume were significantly lower in patients who had been embolized at least 7 days before definitive surgery. Furthermore, large confluent areas of necrosis were significantly more frequent in patients with a larger time span between embolization and surgery. CONCLUSION: Preoperative embolization with PVA in patients with intracranial meningiomas is safe and effective, as it reduces the volume of transfused blood during surgical operation. However, patients should undergo surgery at least 7 days after embolization, as a shorter time interval has been correlated with a longer surgical time and a higher transfused blood volume.

Genealogy of centenarians and their relatives: a study of 12 families.

The longevity is a complex phenomenon in which specific genetic properties seem to play a role. The present study intended to reconstruct the genealogical tree of 12 subjects, being residents of one Northern and one Southern province of Italy, in order to establish the longevity of the ancestors. Detailed studies have been performed in the registry offices and the historic archives. The research method started from the identification of the centenarians on the basis of the documentation of the relevant birth document, it was continued by identifying the documents of birth, marriages and death of the parents of the centenarians. This way we proceeded systematically backwards in time. In addition, we verified the medium life span of the Italian population in the given periods of time, when the centenarians and their ascending lines had lived. These results offer clear historic-statistical evidences for the genetic basis of longevity.

An immunohistochemical study of extracellular matrix proteins laminin, fibronectin and type IV collagen in paediatric glioblastoma multiforme.

AIMS: In the recent decades many studies have been addressed in the literature to assess specific factors related to glioblastoma multiforme (GBM) invasion. However, few studies have evaluated tumour cell's interaction with specific extracellular matrix (ECM) components, and, moreover, there is a lack of information regarding the occurrence of these phenomena in paediatric GBM. METHODS AND RESULTS: ECM proteins were evaluated in six cases of paediatric GBM assessing the immunohistochemical expression of laminin, fibronectin, and type IV collagen. We used a semiquantitative scale, ranging from not detected (zero) to marked (3). Laminin expression was minimal in three cases, moderate in one case, marked and generalised in one patient and marked and focal in the last case. Fibronectin expression was minimal in three patients; moderate immunoreactivity was documented in one case. Conversely, one case was classified as marked with generalised distribution and the remaining case as marked with focal immunostaining. Type IV collagen expression was minimal in three cases, moderate in one, marked with focal reaction in one and marked with generalised reaction in the remaining case. CONCLUSIONS: This study provides additional insights into tumour invasion features of paediatric GBM, as ECM plays a pivotal role in numerous cellular functions during normal and pathological processes. Although based on a limited number of patients, this investigation may serve as a challenge for the management of paediatric GBM, stimulating trials with larger patient numbers aimed at documenting specific factors influencing GBM prognosis.

Does early decompression improve neurological outcome of spinal cord injured patients? Appraisal of the literature using a meta-analytical approach.

STUDY DESIGN: Definitive and unequivocal evidence to support the practice of early or late surgery is still lacking in clinical studies. Accordingly, meta-analysis is one of the few methods that offer a rational, statistical approach to management decision. A review of the clinical literature on spinal cord injury with emphasis on the role of early surgical decompression and a meta-analysis of results was performed. OBJECTIVES: To determine whether neurological outcome is improved in traumatic spinal cord-injured patients who had surgery within 24 h as compared with those who had late surgery or conservative treatment. METHODS: A Medline search covering the period 1966-2000, supplemented with manual search, was used to locate studies containing information on indication, rationale and timing of surgical decompression after spinal cord injuries. The analysis included a total of 1687 eligible patients. RESULTS: Statistically, early decompression resulted in better outcome compared with both conservative (P<0.001) and late management (P<0.001). Nevertheless, analysis of homogeneity showed that only data regarding patients with incomplete neurological deficits who had early surgery were reliable. CONCLUSIONS: Although statistically the percentage of patients with incomplete neurological deficits improving after early decompression appear 89.7% (95% confidence interval: 83.9, 95.5%), to be better than with the other modes of treatment when taking into consideration the material available for analysis and the various other factors including clinical limitations; early surgical decompression can only be considered as practice option for all groups of patients.

Beneficial effects of antibacterial peptide PR-39 in a neonatal murine model of endotoxic shock.

The lethal effects occurring in neonatal (< 24-h old) BALB/c mice after challenge with E. coli lipopolysaccharide (LPS) were significantly counteracted by pretreatment with antibacterial peptide PR-39. Neonatal mice protection was probably related to the depressive effect of PR-39 on production of TNF-alpha known to be the major mediator of the lethal effects of neonatal endotoxic shock. Indeed, TNF-alpha plasmatic levels were consistently lower in pups pretreated with PR-39 compared with controls. Administration 24 h after challenge was no longer effective. Although PR-39 and anti-TNF-alpha doses were ineffective alone, when combined at different ratios protected neonatal mice. The present experiments show the potential use of peptide PR-39 in preventing neonatal endotoxic shock.

Traumatic acute subdural haematomas of the posterior fossa: clinicoradiological analysis of 24 patients.

BACKGROUND: We report 24 patients with a traumatic acute subdural haematoma of the posterior fossa managed between 1997 and 1999 at 8 Italian neurosurgical centres. METHOD: Each centre provided data about patients' clinico-radiological findings, management, and outcomes, which were retrospectively reviewed. FINDINGS: A poor result occurred in 14 patients (58.3%). Ten patients (41.7%) had favourable results. Patients were divided into two groups according to their admission Glasgow Coma Scale (GCS) scores. In Group 1 (12/24 cases; GCS score, > or =8), the outcome was favourable in 75% of cases. In Group 2 (12/12 cases; GCS score, <8), the outcome was poor in 91.6% of cases. Nineteen patients underwent posterior fossa surgery. Factors correlating to outcome were GCS score, status of the basal cisterns and the fourth ventricle, and the presence of supratentorial hydrocephalus. Multivariate analysis showed significant independent prognostic effect only for GCS score (P<0.05). INTERPRETATION: acute posterior fossa subdural haematomas can be divided into two distinct groups: those patients admitted in a comatose state and those with a moderate/mild head injury on admission. Comatose patients present usually with signs of posterior fossa mass effect and have a high percentage of bad outcomes. On the contrary, patients admitted with a GCS of 8 or higher are expected to recover. In these patients the thickness of the haematoma (<1 cm) seems to be a guide to indicate surgical evacuation of the haematoma.

Different methods for anatomical targeting.

AIM: Several procedures are used in the different neurosurgical centers in order to perform stereotactic surgery for movement disorders. At the moment no procedure can really be considered superior to the other. We contribute with our experience of targeting method. METHODS: Ten patients were selected, in accordance to the guidelines for the treatment of Parkinson disease, and operated by several methods including pallidotomy, bilateral insertion of chronic deep brain electrodes within the internal pallidum and in the subthalamic nucleus (18 procedures). INTERVENTIONS: in each patient an MR scan was performed the day before surgery. Scans were performed axially parallel to the intercommissural line. The operating day a contrast CT scan was performed under stereotactic conditions. MEASURES: after digitalization of the MRI images, it was possible to visualize the surgical target and to relate it to parenchimal and vascular anatomic structures readable at the CT examination. The CT scan obtained was confronted with the MR previously performed, the geometrical relation between the different parenchimal and vascular structures and the selected targets were obtained. Stereotactic coordinates were obtained on the CT examination. RESULTS: It was possible to calculate the position of the subthalamic nucleus and of the internal pallidum on the CT scan, not only relating to the intercommissural line, but considering also the neurovascular structures displayed both on the MRI and the CT scans. CONCLUSION: The technique that our group presents consist in an integration between information derived from the CT and the MR techniques, so that we can benefit from the advantages of both methods and overcome the disadvantages.

Large sphenocavernous meningiomas: is there still a role for the intradural approach via the pterional-transsylvian route?

BACKGROUND: Large-sized sphenocavernous meningiomas represent a surgical challenge. Although the role of skull base techniques with combined extra- and intradural steps has been recently emphasized, pure intradural resection tactics via the pterional route constitute the traditional microsurgical approach for resection of such tumours. METHOD: We report the application of the pterional-transsylvian approach in 13 patients with sphenocavernous meningiomas. This series is unique because it includes only patients with tumours exceeding 5 cm in their greatest dimension. FINDINGS: A gross total resection was accomplished in 10 patients (77%). Eight patients had a good outcome, one had a persistent mild hemiparesis, and one died. No recurrences occurred in this group. Three patients (23%) had subtotal resections owing to invasion of the cavernous sinus in one instance and encasement of the middle cerebral artery in the others. Two had a good outcome and one died. In these patients minimal asymptomatic tumour progression was seen 3 and 6 years after surgery. The overall surgical outcome was good in 10 patients (77%), fair in one, and death in two. INTERPRETATION: In our experience, large sphenocavernous meningiomas may be operated on adopting pure intradural resection tactics via the pterional-transsylvian route with rates of gross total removal and surgical complications related to brain retraction or vascular manipulation comparable to those of extensive skull base approaches. The traditional intradural pterional transsylvian approach continues to have a place in the treatment of these lesions.

Growing skull fracture of the posterior cranial fossa and of the orbital roof.

BACKGROUND: Growing Skull Fractures (GSF) are rare complications of head trauma, primarily reported in infancy and early childhood. GSF are commonly located on calvaria, and rarely in other locations, including the skull base. METHOD: In this study, we report two cases of GSF occurring in unusual locations. The first, a 8-month old girl, with a GSF of the suboccipital posterior fossa region, and the second, a 4-year old boy with a GSF of the right orbital roof. Both cases underwent operative treatment of the GSF, with microsurgical dissection and excision of the protruding gliotic brain tissue, watertight duraplasty and autologous bone cranial repair. The authors conducted a Medline search of the relevant English literature from 1966 to 2002. FINDINGS: From the search, three cases of suboccipital posterior fossa region GSF and twelve series of orbital GSF, describing a total of 22 cases, have been found. INTERPRETATION: A survey of the pathogenic mechanisms underlying this entity in these locations is reported. A review of suboccipital posterior fossa and orbital roof GSF cases, of nosological, ophthalmological and neurological data, neuroradiological and operative findings, and results of different treatment strategies are described.

Assistance of intraoperative microvascular Doppler in the surgical obliteration of spinal dural arteriovenous fistula: cases description and technical considerations.

BACKGROUND: Intraoperative microvascular Doppler may be valuable in assisting in the surgical obliteration of dural arteriovenous fistula of the spinal cord. It enables identification, through flow spectrum analysis, of the anatomic components and haemodynamic features of this type of vascular malformation. METHODS: In two cases, intraoperative microvascular Doppler was used to assist in the surgical obliteration of dural arteriovenous fistula of the spinal cord. The fistulas were identified prior to the dura opening, and for this only minimally invasive surgery was required. Direct recordings of the arterialised draining vein and the nidus of the fistula demonstrated a pathological spectrum caused by the arterial supply and the disturbed venous outflow in which a high-resistance flow pattern and low diastolic flow resembling an arterial-like flow velocity were observed. FINDINGS: The fistulas were obliterated by interruption of the draining vein, and Doppler measurements provided information on flow velocity changes in the medullary veins from an arterial to a venous pattern. The absence of any residual flow in the draining vein confirmed successful haemodynamic treatment. INTERPRETATION: Intraoperative microvascular Doppler recording is valuable assistance in surgical closure of spinal arteriovenous fistula.

Radicular compression by lumbar intraspinal epidural gas pseudocyst in association with lateral disc herniation. Role of the posterior longitudinal ligament.

Among unusual abnormalities of the lumbar spine reported since the introduction of Computed Tomography (CT), the presence of gas lucency in the spinal canal, known as vacuum phenomenon, is often demonstrated. On the contrary, epidural gas pseudocyst compressing a nerve root in patients with a lateral disc herniation has rarely been reported. We report a case of a 44-year-old man who experienced violent low back pain and monolateral sciatica, exacerbated by orthostatic position, one week before admission. A lumbosacral spine CT showed the presence of vacuum phenomenon associated with a degenerated disc material and a capsulated epidural gas collection with evidence of root compression. A microsurgical interlaminar approach was carried out and, before the posterior longitudinal ligament was entered, a spherical "bubble" compressing the nerve roots was observed. The capsulated pseudocyst was dissected out, peeled off and excised en bloc. A large part of the posterior longitudinal ligament and the lateral disc herniation were removed. Postoperatively the patient was completely free of symptoms. The mechanism of exacerbation of pain was probably due to the increased radicular compression in the upright posture and, besides the presence of a lateral disc herniation, could be related to a pneumatic squeezing of gas from the intervertebral space into the well capsulated sac by the solicitated L4-L5 motion segment. Histological study of the wall of the pseudocyst showed the presence of fibrous tissue identical to the ligament. We conclude that, in case of a lumbar disc herniation, it is recommended to perform a complete microdiscectomy and an accurate removal of the involved portion of posterior longitudinal ligament in order to prevent pseudocystic formations.

Endoscopic fenestration of symptomatic septum pellucidum cysts: three case reports with discussion on the approaches and technique.

OBJECTIVES: We describe three patients with symptomatic septum pellucidum cysts treated by endoscopic fenestration and discuss the different endoscopic approaches to these cysts. CLINICAL PRESENTATION: The patients are an 8-year-old boy, a 7-year-old boy and a 21-year-old woman; this last also had a right frontal cavernous angioma and a pituitary microadenoma. All patients presented with headache, associated with vomiting in two and behavioral changes in one. In all cases magnetic resonance showed a septum pellucidum cyst. INTERVENTION: Two patients were operated upon by posterior approach through a right occipital burr hole and underwent fenestration from the right occipital horn to the cyst, with a second fenestration from the cyst to the left lateral ventricle in one. Another patient underwent microsurgical removal of a right frontal cavernoma and endoscopic cyst fenestration with both lateral ventricles through a right frontal craniotomy. Postoperatively, headache and vomiting resolved in all cases and behaviour changes improved in one. CONCLUSIONS: Endoscopic fenestration is the treatment of choice for septum pellucidum cysts, where it results in immediate relief of the mass effect of the cyst and in the remission of the associated symptoms. We suggest a posterior approach through a right occipital burr hole. It allows one to easily cannulate the occipital horn, which is usually larger than the frontal one, thus avoiding the risk of damaging the vascular and neural structures surrounding the foramen of Monro. Besides, the endoscopic trajectory is in our opinion more direct. The two-window technique, with fenestration of the cyst into both lateral ventricles, improves the chances of long-term patency.

A preliminary study of angiogenesis in paediatric glioblastoma multiforme and its correlation with survival.

OBJECTS: There is a distinct challenge in bringing modern insights into glial tumour genesis to bear on improved outcomes for patients. Insights provided by neuroncological, neuroradiological, neuropathological, and neurosurgical investigations may offer significant advantages in the management of paediatric GBM. The goal of this study was to evaluate angiogenesis as a potential indicator of survival in paediatric glioblastoma multiforme (GBM). METHODS: Angiogenesis was evaluated in six cases of paediatric GBM with multiple criteria, including contrast enhancement on preoperative CT scan, histological vascular hyperplasia (VH) and endothelial proliferation (EP) and immunohistochemical tenascin-C (TN-C) expression. We employed a semiquantitative scale, ranging from not detected (zero) to marked (+3), for each investigational parameter. We evaluated the influence of angiogenesis on survival in each case. CONCLUSIONS: In this preliminary study, angiogenesis provided information that correlated with survival, albeit in a limited number of patients. As we gain better understanding of the molecular biology of brain tumours, with the multitude of genetic alterations and growth factors new therapeutic approaches may emerge, which may hold the promise for cure.

Trigeminal pain caused by a cerebellopontine-angle lipoma. Case report and review of the literature.

A 16-year-old girl complained of 2-year history of right facial pain, episodic vertigo and progressive hearing loss in the right ear. The facial pain was described as an episodic lancinating event confined to the second and third branch of the right trigeminal nerve. Computed tomography and magnetic resonance imaging revealed a 2 cm lesion in the right cerebellopontine-angle. At surgery, a soft, yellowish mass was found incorporating the 7th and 8th cranial nerves. The anterior-inferior cerebellar artery (AICA) was displaced medially and pushed into the sensory portion of the trigeminal nerve root, causing vascular compression. The hearing loss remained unchanged. The trigeminal pain disappeared over a period of several weeks. Patients can be harmed in an attempt to remove these neurovascular nonmalignant, generally non growing, fatty vascular lumps. Only a partial, meticulous removal should be performed with a maximum effort to decompress the affected nerve.

Immunohistochemical TRF1 expression in human primary intracranial tumors.

BACKGROUND: The telomeric-repeat binding factor (TRF1) participates in a physiological homeostatic mechanism controlling telomere shortening by inhibiting telomerase activity: down-regulation of TRF1 expression results in telomere elongation and may be involved in cell immortalization. PATIENTS AND METHODS: To determine the TRF1 expression by immunohistochemistry (IHC) in human brain tumors, a cohort of 20 consecutive flash-frozen surgical specimens (14 meningiomas and 6 anaplastic astrocytomas (AA)) were collected. RESULTS: Variable levels of TRF1 expression in 12 out of the 14 (87.5%) meningioma samples were observed. By contrast, no expression of TRF1 in tissue samples from AA (p = 0.008) was detected. Positive TRF1 cells were usually more differentiated (less atypical features) and Ki67 negative (inverse statistical association, chi2 = p < 0.001). CONCLUSION: We demonstrated, for the first time, that routine IHC techniques are capable of identifying TRF1 expression in intracranial tumors, which is heterogeneously expressed in meningiomas, but absent in AA. Although these preliminary observations need confirmation from larger studies, the TRF1 status in intracranial tumors might become of prognostic value.

Traumatic intracerebellar hemorrhagic contusions and hematomas.

BACKGROUND: Traumatic intracerebellar hemorrhagic contusions and hematomas (TIHC) are unusual lesions and their surgical management remains controversial. METHODS: From January 1990 to July, 1998, 3290 patients underwent computed tomography for acute head trauma at our Institution. Eighteen patients (0.54%) were retrospectively identified as harboring TIHC. Patients were divided into two groups. In Group I (n=78) GCS at admission was > or = 9. Seven patients presented with isolated TIHC and one with an associated supratentorial lesion. Three patients exhibited an evolving clinico-radiological course. In Group II patients (n=10) GCS at admission was < or = 7. All but one presented with severe supratentorial lesions and associated brainstem signs. RESULTS: In group I six patients had their TIHC managed conservatively, and two were operated on, and all recovered completely. In group II, two patients were operated on. The outcome was poor in 90% of cases. CONCLUSIONS: TIHC constitute a protean clinico-pathological entity. Non-comatose patients with intracerebellar clots less than 3 cm in diameter should be treated conservatively and expected to make a good recovery. Surgery is indicated for larger hematomas causing cisternal and IV ventricle compression ab initio or as a result of their secondary evolution. In severely ill patients admitted comatose, it is generally the primary brain stem damage and the concomitant severe supratentorial lesions to dictate the prognosis. In these cases obliteration of the posterior fossa cisterns is the most reliable indicator of poor outcome.