Andrea Di Cristofori

Surgical brain metastases: management and outcome related to prognostic indexes: a critical review of a ten-year series.

Brain metastasis are the most common neoplastic lesions of the nervous system. Many cancer patients are diagnosed on the basis of a first clinical presentation of cancer on the basis of a single or multiple brain lesions. Brain metastases are manifestations of primary disease progression and often determine a poor prognosis. Not all patients with a brain metastases undergo surgery: many are submitted to alternative or palliative treatments. Management of patients with brain metastases is still controversial, and many studies have been developed to determine which is the best therapy. Furthermore, management of patients operated for a brain metastasis is often difficult. Chemotherapy, stereotactic radiosurgery, panencephalic radiation therapy, and surgery, in combination or alone, are the means most commonly used. We report our experience in the management of a ten-year series of surgical brain metastasis and discuss our results in the preoperative and postoperative management of this complex condition.

Gene expression profile analysis of human mesenchymal stem cells from herniated and degenerated intervertebral discs reveals different expression of osteopontin.

Gene expression analysis provides an effective methodology to identify clinically relevant genes implicated in intervertebral disc (IVD) pathology. The analysis of gene profile in mesenchymal stem cells (MSCs) from human herniated IVD (H-IVD) and degenerated IVD (D-IVD) has not yet been investigated. We present in this study a characterization of MSCs isolated from clinically categorized H-IVD and D-IVD disc samples. H-IVD-MSCs and D-IVD-MSCs showed multipotent mesenchymal differentiation ability, expressing positivity for adipogenic, osteogenic, and chondrogenic markers with an immunophenotypical profile representative of MSCs. FACS analyses revealed a higher expression of CD44 in D-IVD-MSCs compared to H-IVD-MSCs. Gene expression profile revealed that most genes under investigation displayed large variations and were not significantly different in the two types of analyzed IVD-MSCs. Conversely, the gene expression of osteopontin (OPN), a protein involved in bone matrix mineralization and extracellular matrix destruction, was found markedly increased (more than 400-fold) in D-IVD-MSCs compared to H-IVD-MSCs. Moreover, the OPN protein expression was detectable only in D-IVD-MSCs, and its levels were directly related with D-IVD severity. These findings suggest that an abnormal expression of OPN in D-IVD-MSCs occurs and plays a pivotal role in the pathophysiological process of human disc degeneration. We speculate that the regulation of the OPN pathway might be a therapeutic target to counteract disc degeneration.

The Oncofetal Protein IMP3: A Novel Grading Tool and Predictor of Poor Clinical Outcome in Human Gliomas

Morphologic criteria illustrated in WHO guidelines are the most significant prognostic factor in human gliomas, but novel biomarkers are needed to identify patients with a poorer outcome. The present study examined the expression of the oncofetal protein IMP3 in a series of 135 patients affected by high-grade (grade III and IV) gliomas, correlating the results with proliferative activity, molecular parameters, and clinical and follow-up data. Overall, IMP3 expression was higher in glioblastomas (68%) than in grade III tumors (20%, P < 0.0001), and IMP3-positive high-grade gliomas showed a shorter overall and disease-free survival than negative ones (P = 0.0002 and P = 0.006, resp.). IMP3 expression was significantly associated with the absence of mutations of IDH1 gene (P = 0.0001) and with the unmethylated phenotype of MGMT in high-grade gliomas (P = 0.004). High Ki67 levels were correlated with better prognosis in glioblastomas but IMP3 expression was not correlated with the proliferation index. These findings confirm the role of IMP3 as a marker of poor outcome, also in consideration of its association with IDH1 wild-type phenotype and MGMT unmethylated status. The data suggest that IMP3 staining could identify a subgroup of patients with poor prognosis and at risk of recurrence in high-grade gliomas.

Is Neurosurgery Ready for Cisternostomy in Traumatic Brain Injuries

LETTER: I read with interest the article by Giammattei et al 1 dealing with the use of cisternostomy in a case of traumatic brain injury with intractable intracranial hypertension. They described the case of a young man with severe brain swelling treated with cisternostomy, which allowed them to achieve good control of the intracranial pressure and avoid decompressive craniectomy. The idea of cisternostomy is original, and it is based on an alternative view about the pathophysiologic mechanisms involved in cerebrospinal fluid (CSF) circulation and brain swelling. The ancient paradigms on CSF circulation postulated by Dandy are coming to an end due to the huge work of Bulat, Ore skovi c, and Klarica. In their works they demonstrated how CSF is produced by the brain parenchyma and reabsorbed by the perivascular Virchow-Robin spaces. In traumatic brain injuries, brain edema is believed by some authors to be due to an obstruction of the reabsorption of CSF and to the shift of CSF from the subdural space into the parenchyma. On the basis of these assumptions, Cherian ideated and first described cisternostomy, which is a surgical treatment that allows restoration of the normal CSF pathways involved in reabsorption of CSF through the retrieval of CSF from the basal cisterns and reduction of the amount of CSF shifted into the brain parenchyma. Considering these premises, several points need some reflection:

Optic Radiation Diffusion Tensor Imaging Tractography: An Alternative and Simple Technique for the Accurate Detection of Meyer's Loop

BACKGROUND The optic radiation (OR) is a white matter bundle with a very complex anatomy. Its anterior component bends sharply around the tip of the temporal horn, forming the Meyers loop (ML), the sparing of which during surgery is crucial to preserve visual function. Defining its exact anatomy and accurately identifying its position remain challenging, even with diffusion tensor imaging (DTI) tractography and the most refined tracking procedure. We have developed an alternative tracking technique to detect the ML position. METHODS We performed DTI studies in 26 patients undergoing resection of a temporo-parieto-occipital lesion. We then reconstructed the ORs of each patient using 2 techniques (the first developed by our team, the other taken from the literature), using the same tracking software and parameters. We evaluated the accuracy of each technique measuring 3 distances that define the ML position. We created 5 data groups and compared the 2 techniques. Finally, we compared our results with the results from 8 anatomic dissection studies and other tractographic studies. RESULTS Our findings show that our technique allows a more accurate definition of the ML position. We found a statistically significant (P < 0.05) difference for all the distances between the 2 techniques; our results resemble those obtained in dissection studies. Our technique is also easy to perform and repeatable. CONCLUSIONS Our tracking technique may be of marked interest for the evaluation and anatomic definition of the ML position, particularly for neurosurgeons approaching the anterior temporal region.

IMP3 expression in NSCLC brain metastases demonstrates its role as a prognostic factor in non-neuroendocrine phenotypes

Brain metastases from NSCLC are associated with a poor prognosis, and local radiotherapy is the most effective therapeutic strategy. The oncofetal protein IMP3 has been studied extensively, and evidence suggests that its expression is related to shorter overall survival and a more aggressive phenotype in solid malignancies. Here, the prognostic role of IMP3 was investigated in a cohort of patients with NSCLC brain metastases in correlation with survival and tumor histotype. A series of 42 NSCLC brain metastases samples was analyzed by tissue microarray and immunohistochemical staining for IMP3. IMP3 expression was associated with shorter overall survival in the whole series and in subgroups of metastases from non-neuroendocrine pulmonary malignancies and adenocarcinoma metastases. These results indicated that IMP3 is a strong prognostic factor in non-neuroendocrine brain metastases and in particular in patients with adenocarcinoma metastases.

Subacute posttraumatic ascending myelopathy (SPAM): A potential complication of subarachnoid shunt for syringomyelia?

Context: Treatment of primary spinal syringomyelia is still controversial. Among others, shunting syrinx fluid to the subarachnoid, peritoneal or pleural space has been utilized with varying success. Shunt obstruction, migration, and infection represent the most common complications of these procedures. Findings: The authors present the case of an 81-year-old woman who developed an unusual neurological deterioration resembling a subacute posttraumatic ascending myelopathy (SPAM) after the insertion of a syringosubarachnoid shunt for the treatment of slow-growing D10 syringomyelia. Conclusion/Clinical Relevance: To date, no cases of SPAM secondary to the insertion of a syringosubarachnoid shunt for the treatment of syringomyelia have been reported. The potential pathogenesis related to this phenomenon is discussed.

Acute Intracranial Posttraumatic CSF Hypotension in a Child: Case Report on a Difficult Craniofacial Trauma

We report the case of a 12-year-old child involved in an accident during a horse competition, with a severe head trauma, who developed acute intracranial hypotension due to a massive sphenoidal sinus and ethmoidal cerebrospinal fluid leakage. The patient presented with acute loss of vision and brain anoxic ischemic lesions associated with contusions, and internal carotid artery dissection. Anoxic ischemic lesions and carotid artery dissection can be explained by airways obstruction and direct mechanical trauma; however, loss of vision is not clearly related with a direct cause. Three mechanisms can be hypothesized to be responsible for the loss of vision. One involves acute intracranial hypotension caused by massive cerebrospinal fluid leakage determining a lowering of supratentorial structures and stretching the optic cranial nerves; the second relates to initial hypoxia due to airway obstruction; and the third involves a direct mechanical stress on the injured structures. Interestingly, the 3 pathogenetic mechanics are not mutually exclusive but their effects amplify each other. To the best of our knowledge, this is the first report describing a case of acute intracranial hypotension in a craniofacial injury.

Selection of Elderly Meningioma Patients for Surgery Using a Clinical-Radiological Grading System as a Predictor of Outcome

Based on a retrospective study, in a previous report we developed a grading system, called ‘Clinical Radiological Grading System’ (CRGS), in order to standardise surgical indications in patients older than 70 years affected by intracranial meningiomas. Various prognostic factors were taken into consideration: clinical conditions, comorbidities, neurological status, size and size of the lesion and peritumoral edema. We then performed a prospective cross-sectional study including 90 consecutively recruited patients (from 1990 to 2000), 70 years of age or older, affected by meningiomas in whom the decision whether to operate was based on the CRGS score. Our findings showed that patients with a score lower than 10 had a poor prognosis regardless of surgical treatment, those with a score between 10 and 12 had a prognosis positively influenced by surgery, and those with a score higher than 12 had a good prognosis regardless of surgical treatment. A further validation of our scale has been made in a second prospective study, which is discussed in the present chapter. We also analyzed similar studies performed by other authors and compare our grading system to alternative scores which have been created afterwards.