Stem cell salvage of injured peripheral nerve.

We previously developed a collagen tube filled with autologous skin-derived stem cells (SDSCs) for bridging long rat sciatic nerve gaps. Here we present a case report describing a compassionate use of this graft for repairing the polyinjured motor and sensory nerves of the upper arms of a patient. Preclinical assessment was performed with collagen/SDSC implantation in rats after sectioning the sciatic nerve. For the patient, during the 3-year follow-up period, functional recovery of injured median and ulnar nerves was assessed by pinch gauge test and static two-point discrimination and touch test with monofilaments, along with electrophysiological and MRI examinations. Preclinical experiments in rats revealed rescue of sciatic nerve and no side effects of patient-derived SDSC transplantation (30 and 180 days of treatment). In the patient treatment, motor and sensory functions of the median nerve demonstrated ongoing recovery postimplantation during the follow-up period. The results indicate that the collagen/SDSC artificial nerve graft could be used for surgical repair of larger defects in major lesions of peripheral nerves, increasing patient quality of life by saving the upper arms from amputation.

The importance of predicting factors in the surgical outcome of peripheral nerve sheath tumors.

OBJECTIVE: Peripheral nerve sheath tumors (PNSTs) are tumors arising from the neural sheath cells. Surgery plays a central role in the management of this disease, with the purpose of obtaining radical tumor's resection and at the same time providing the best outcome. We retrospectively analyzed 53 PNSTs in 42 patients in an attempt to identify some factors that may improve surgical outcome. MATERIAL AND METHODS: Clinical, histologic, and imaging data of 42 patients with PNSTs treated at our Institute between 2001 and 2012 were collected and analyzed. We evaluated the outcome 1 month and 6 month after surgery using three clinical parameters (pain, motor deficits, and sensory deficits) in relation to different histotypes, the presence of neurofibromatosis type 1, tumor location, and duration of symptoms before treatment. RESULTS: The best functional results were observed in patients having neurofibromas; the worst outcomes were observed in patients with malignant PNSTs. The other factors were not associated with outcome. CONCLUSION: The timing of surgery is the most important predictive factor of surgical outcome, being the only factor that allows to improve the outcome. With the current study, we want to stress the importance of treating PNSTs as soon as possible to provide the best outcome possible.

The long pentraxin PTX3 as a correlate of cancer-related inflammation and prognosis of malignancy in gliomas.

Inflammation is a component of glioma microenvironment. PTX3 is a component of the humoral arm of innate immunity and a candidate marker of inflammation. In the present study we assessed the expression of PTX3 in gliomas by immunohistochemistry. PTX3 expression differed across low and high-grade tumors based on histopathological diagnosis and clinical severity, positively correlating with tumor grade and severity. In a multivariate logistic regression model, only the PTX3 score was significantly associated with the presence of a high-grade tumor. Thus, PTX3 may represent a new marker of cancer-related inflammation and glioma malignancy.

Transphenoidal surgery in acromegalic patients: anatomical considerations and potential pitfalls.

BACKGROUND: Transphenoidal surgery is an effective treatment for acromegalic patients with growth hormone (GH) producing pituitary adenomas. Since acromegaly is a systemic disease which causes multiple bony alterations, we hypothesized that it could affect the sphenoid sinus anatomy. The aim of the study was to determine whether acromegalic patients have sphenoid sinus alterations with potential surgical impact. METHODS: Fourty-six consecutive patients (23 acromegalics-GH group, 23 non-acromegalics-nGH group) undergoing transphenoidal surgery were included in this study. Pre-operative volumetric CT scan of the head was used to assess the following anatomic characteristics: type of sphenoid sinus (sellar, pre-sellar, conchal); number of intrasphenoid septa; number of carotid-directed septa; intercarotid distance; depth of the sphenoid sinus; depth and size of the sella. RESULTS: The sphenoid sinus was of the pre-sellar/conchal type in 26 % of the patients with acromegaly (n = 23) versus 9 % of the patients of the nGH group (n = 23). The number of intrasphenoid septations was significantly higher in the GH group than in the nGH group (P = .03). Interestingly, the intercarotid distance was smaller in GH patients than in nGH displaying a trend toward significance (P = .05). The sphenoid bone was deeper in the GH group as compared to the nGH group (P = .01) but the distance sphenoid sinus-sella was reduced (P < .01). Finally, the sella was not deeper, nor larger in acromegalic patients. CONCLUSIONS: The sphenoid sinus of acromegalic patients resulted in being deeper, characterized by more septa and by a reduced intercarotid distance. These alterations deserve special pre- and intraoperative care, being potentially responsible for surgical difficulties.

Protective action of NDP-MSH in experimental subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is still a major cause of morbidity and mortality. α-Melanocyte stimulating hormone (α-MSH) and other melanocortin peptides exert potent neuroprotective action and they might modulate key molecules involved in SAH-induced vasospasm. The aim of this research was to determine whether treatment with the α-MSH analog Nle4,DPhe7-α-MSH (NDP-MSH) exerts protective effects in experimental SAH in the rat. Initial experiments examined effects of NDP-MSH on the basilar artery phenotype in the absence of injury. In these tests intrathecal injection of small concentrations (10ng) of the peptide induced a tolerant phenotype similar to that observed after ischemic preconditioning. Then the effect of systemic treatment with NDP-MSH (100µg i.v.) on experimental SAH was evaluated. SAH was induced by a single-blood injection into the cisterna magna. The basilar artery phenotype was examined at 4h and the artery caliber at 5days following SAH. Expression of 96 genes was analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR) using Custom Taqman Low-Density Arrays. Four hours after SAH, the transcriptional profile of the basilar artery was deeply disrupted. Transcript alteration included genes involved in inflammation, stress response, apoptosis, and vascular remodeling. Treatment with NDP-MSH prevented most of these transcription changes and decreased phosphorylation of extracellular-signal-regulated kinases (ERK1/2) and inhibitor protein IκBα. Vasospasm on day 5 was significantly reduced by NDP-MSH administration. These results combine with others on CNS inflammation to suggest that the melanocortins could be safe and effective therapeutic candidates to treat SAH-related complications.

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.

Adjuvant temozolomide chemotherapy for treatment of papillary tumor of the pineal region.

BACKGROUND: We present a personal case of papillary pineocytoma in a 42-year-old woman. METHODS: The lesion was first treated surgically both for diagnostic aims and for resolution of the mass effect causing hydrocephalus and correlated neurological disturbances. Because the tumor recurred after surgery and radiotherapy, we decided to further treat the patient with chemotherapy, in particular with temozolomide. RESULTS: Currently, almost 9 years after the first treatment, the patient is symptom-free and follow-up magnetic resonance imaging shows no tumor recurrence. CONCLUSION: Although surgery should be considered the first-choice therapy, we think that temozolomide can be a valid option in case of recurrence of these rare tumors.

Endoscopic endonasal removal of a cavernous hemangioma of the orbital apex.

BACKGROUND: Cavernous hemangioma are the most common benign lesions of the orbit. Their surgical resection is still challenging and several surgical approaches have been proposed. CASE DESCRIPTION: We present the case of a 59-year-old woman with a cavernous hemangioma of the orbital apex, which was diagnosed incidentally. The hemangioma was extraconal and involved mainly the medial orbital apex; it also extended to the pterygoid fossa, to the middle fossa, to the maxillary and sphenoid sinuses. The surgical resection was performed by a pure endoscopic transphenoidal, transmaxillary, transethmoidal approach, achieving a total removal. The patient had a transient and incomplete paresis of the VI cranial nerve on the left side and did not experience other postoperative complications. CONCLUSION: The endoscopic endonasal approach proved successful in the management of this case and it should be considered in the surgical management of extraconal orbital apex lesions with medial or inferior extension.

Endoscopic transsphenoidal optic nerve decompression: an anatomical study.

PURPOSE: The endoscopic transnasal, transsphenoidal approach is considered by many a valid option to reach the sellar region and, in selected cases, to decompress the optic nerve. However, few data are available in literature about the real effectiveness of the procedure and the extent of nerve decompression needed to obtain a clinical result. The aim of this anatomical study was to describe the most important landmarks of the endoscopic transsphenoidal approach to the optic nerve. METHODS: Six silicone-injected cadaver heads were dissected via the endoscopic transnasal approach, performing a bilateral optic nerve decompression. The lateral optocarotid recess (OCR) and optic canal were identified in each case. Moreover, the relationship between the ophthalmic artery at its origin and the optic nerve was examined. RESULTS: Twelve decompressions of the optic nerve were performed, obtaining the following measurements: intercarotid distance 12 mm ± 1.5, median length of OCR 5 mm ± 1 and average length of optic nerve decompression 15 mm ± 2. The ophthalmic artery was observed emerging from the internal carotid artery (ICA) medially in six cases, ventrally in four cases and laterally in two cases. CONCLUSION: A wide optic nerve decompression may be obtained with transsphenoidal approach. However, the risk of ophthalmic artery injury seems to be more relevant than with supratentorial approaches, due to the intimate relationship between artery and nerve on its inferior surface. Knowledge of anatomical landmarks, such as lateral OCR and the position of the ophthalmic artery, is useful to prevent this injury.

Intraoperative use of diffusion tensor imaging fiber tractography and subcortical mapping for resection of gliomas: technical considerations.

Resection of lesions involving motor or language areas or pathways requires the intraoperative identification of functional cortical and subcortical sites for effectively and safe guidance. Diffusion tensor (DT) imaging and fiber tractography are MR imaging techniques based on the concept of anisotropic water diffusion in myelinated fibers, which enable 3D reconstruction and visualization of white matter tracts and provide information about the relationship of these tracts to the tumor mass. The authors routinely used DT imaging fiber tractography to reconstruct various tracts involved in the motor and/or language system in a large series of patients with lesions involving the motor and/or language areas or pathways. The DT imaging fiber tractography data were loaded into the neuronavigational system and combined intraoperatively with those obtained from direct electrical stimulation applied at the subcortical level. In this paper the authors report the results of their experience, describing the findings for each tract and discussing technical aspects of the combined use as well as the pitfalls.

Human glioma tumors express high levels of the chemokine receptor CX3CR1.

The chemokine receptor CX3CR1 and its cognate ligand CX3CL1 (also known as fractalkine), are involved in central nervous system pathophysiology, in particular, in the cross-talk between neurons and microglia. It was therefore important to investigate the expression of CX3CR1 in gliomas, the most frequently occurring, malignant brain tumors. In a consecutive series of 70 patients with primary, central nervous glial tumors, CX3CR1 was highly expressed in tumor cells as assessed by RT-PCR mRNA and protein levels, and by immunohistochemistry, while the corresponding normal cells were negative. Receptor immuno-positivity did not correlate with histology, grade, chromosomal (1p,19q) deletion, or with methylation of the DNA repair gene promoter MGMT (O6-methylguanine-DNA methyltransferase). Thus, CX3CR1 expression is a frequent event in gliomas, irrespective of tumor classification and clinical severity. The molecular basis underlying CX3CR1 up-regulation and its functional biological significance remain to be determined.

Intraoperative mapping for tumor resection.

This article describes the rationale, indications, and modality for intraoperative brain mapping for safe and effective surgical removal of tumors located within functional brain areas.

Intraoperative mapping and monitoring of brain functions for the resection of low-grade gliomas: technical considerations.

Low-grade gliomas ([LGGs] WHO Grade II) are slow-growing intrinsic cerebral lesions that diffusely infiltrate the brain parenchyma along white matter tracts and almost invariably show a progression toward malignancy. The treatment of these tumors forces the neurosurgeon to face uncommon difficulties and is still a subject of debate. At the authors' institution, resection is the first option in the treatment of LGGs. It requires the combined efforts of a multidisciplinary team of neurosurgeons, neuroradiologists, neuropsychologists, and neurophysiologists, who together contribute to the definition of the location, extension, and extent of functional involvement that a specific lesion has caused in a particular patient. In fact, each tumor induces specific modifications of the brain functional network, with high interindividual variability. This requires that each treatment plan is tailored to the characteristics of the tumor and of the patient. Consequently, surgery is performed according to functional and anatomical boundaries to achieve the maximal resection with maximal functional preservation. The identification of eloquent cerebral areas, which are involved in motor, language, memory, and visuospatial functions and have to be preserved during surgery, is performed through the intraoperative use of brain mapping techniques. The use of these techniques extends surgical indications and improves the extent of resection, while minimizing the postoperative morbidity and safeguarding the patient's quality of life. In this paper the authors present their paradigm for the surgical treatment of LGGs, focusing on the intraoperative neurophysiological monitoring protocol as well as on the brain mapping technique. They briefly discuss the results that have been obtained at their institution since 2005 as well as the main critical points they have encountered when using this approach.

Schilder's disease: non-invasive diagnosis? :A case report and review.

Schilder's disease, or myelinoclastic diffuse sclerosis, is a rare disorder characterised by an inflammatory white matter plaque of demyelination. Clinical signs and symptoms might be atypical for early multiple sclerosis and at imaging the lesion is easily taken for a brain tumour. Regardless of the use of Poser's criteria for clinical diagnosis of Schilder's disease proposed in 1986, diagnostic difficulties are still present, as evidenced by the many reported cases in the English literature revised (Pubmed indexed, period 1998-2008). It clearly emerges that neuroradiological features, observable in additional magnetic resonance sequences are crucial, besides the consideration of Poser's criteria, in differentiating between demyelinating lesions and brain tumours. A 29-year-old female patient is presented, where a careful evaluation of both the clinical and radiological features, which might have been at a first glance misleadingly suggestive for a brain tumour, allowed non-invasive diagnosis of Schilder's disease.

Anterior cranial base reconstruction following a complicated nasal septoplasty.

We present a 29 year old man who had unilateral visual loss and 3rd cranial nerve palsy after a nasal septoplasty. Nasal packing was extending from the right nasal cavity into the right frontal lobe passing through the right orbit. A combined trans-cranial and endoscopic endonasal approach was performed to safely remove the nasal packing and to achieve a leak-proof sealing of the anterior cranial base. This surgical technique proved successful in the management of this unique complication and should be considered in the surgical management of foreign body removal from the anterior cranial base.

Patients with moderate head injury: a prospective multicenter study of 315 patients.

OBJECTIVE: To analyze the risk factors of worst outcome associated with moderate head injury. METHODS: Data on patients with moderate head injury were collected prospectively in 11 Italian neurosurgical units over a period of 18 months. Patients older than 18 years with blunt head injury and at least one Glasgow Coma Scale (GCS) score between 9 and 13 were enrolled. The outcome was determined at 6 months using the Glasgow Outcome Scale. RESULTS: We analyzed 315 patients. Initial computed tomographic scans showed a diffuse injury type I or II in 63%, a mass lesion in 35%, and traumatic subarachnoid hemorrhage in 42% of the patients. The risk of progression toward a mass lesion was 23% when the admission computed tomographic scan showed diffuse injury type I or II. An emergency craniotomy was performed in 22% of the patients, delayed surgery was performed in 14%, and both were performed in 25%. A favorable outcome was obtained in 74% of the patients. When the GCS score was 9 or 10, the predictor of worst outcome was a motor GCS score of 4 or lower (odds ratio [OR], 8.08; 95% confidence interval [CI], 1.22-67.35; P = 0.008), but when the GCS score was 11 to 13, the factors associated with worst outcome were neuroworsening (OR, 3.43; 95% CI, 1.45-8.17; P = 0.002), seizures (OR, 7.94; 95% CI, 1.18-64.48; P = 0.02), and medical complications (OR, 4.24; 95% CI, 1.74-10.33; P = 0.0006). CONCLUSION: There is a high percentage of surgery and worsening on computed tomographic scans in patients with moderate head injury. Neuroworsening, seizures, and medical complications as outcome predictors were more strongly associated with a GCS score of 11 to 13, whereas a low motor GCS score was more outcome-related in patients with GCS scores of 9 and 10.

Who is who: areas of the brain associated with recognizing and naming famous faces.

OBJECT: It has been hypothesized that specific brain regions involved in face naming may exist in the brain. To spare these areas and to gain a better understanding of their organization, the authors studied patients who underwent surgery by using direct electrical stimulation mapping for brain tumors, and they compared an object-naming task to a famous face-naming task. METHODS: Fifty-six patients with brain tumors (39 and 17 in the left and right hemispheres, respectively) and with no significant preoperative overall language deficit were prospectively studied over a 2-year period. Four patients who had a partially selective famous face anomia and 2 with prosopagnosia were not included in the final analysis. RESULTS: Face-naming interferences were exclusively localized in small cortical areas (< 1 cm2). Among 35 patients whose dominant left hemisphere was studied, 26 face-naming specific areas (that is, sites of interference in face naming only and not in object naming) were found. These face naming-specific sites were significantly detected in 2 regions: in the left frontal areas of the superior, middle, and inferior frontal gyri (p < 0.001) and in the anterior part of the superior and middle temporal gyri (p < 0.01). Variable patterns of interference were observed (speech arrest, anomia, phonemic, or semantic paraphasia) probably related to the different stages in famous face processing. Only 4 famous face-naming interferences were found in the right hemisphere. CONCLUSIONS: Relative anatomical segregation of naming categories within language areas was detected. This study showed that famous face naming was preferentially processed in the left frontal and anterior temporal gyri. The authors think it is necessary to adapt naming tasks in neurosurgical patients to the brain region studied.

Transient inhibition of motor function induced by the Cavitron ultrasonic surgical aspirator during brain mapping.

OBJECTIVE: We report, for the first time, the occurrence of interference between a Cavitron ultrasonic surgical aspirator (CUSA) and intraoperative brain mapping performed by direct electrical stimulation (DES). METHODS: Intraoperative polygraphic recordings (electrocorticogram and electromyogram) were gathered from a 44-year-old patient harboring a recurrent Grade II oligoastrocytoma operated on with the aid of a CUSA and DES. RESULTS: Simultaneous use of CUSA and DES at the subcortical level in proximity to the corticospinal tract brought about the abolition of previously evident motor responses. This abolition was fully reversible after the CUSA was turned off. An analogous pattern of motor response inhibition was evident when the DES was applied cortically and the CUSA was used subcortically close to motor pathways. Interestingly, the authors had already observed a similar phenomenon in many patients when the CUSA was used for resection of lesions located within or in proximity to subcortical language pathways. In this setting, the CUSA induced transient speech disturbances that were confirmed afterwards by the DES. This interference with language and motor mapping might be interpreted as a transitory inhibition of axonal conduction. CONCLUSION: The clinical significance of this interference is relevant when the CUSA and DES are used simultaneously for motor mapping because the CUSA can decrease the sensitivity of the brain mapping technique. Further studies will be required to determine the neurophysiological mechanism underlying this interference.

Motor and language DTI Fiber Tracking combined with intraoperative subcortical mapping for surgical removal of gliomas.

Preoperative DTI Fiber Tracking (DTI-FT) reconstruction of functional tracts combined with intraoperative subcortical mapping (ISM) is potentially useful to improve surgical procedures in gliomas located in eloquent areas. Aims of the study are: (1) to evaluate the modifications of fiber trajectory induced by the tumor; (2) to validate preoperative DTI-FT results with intraoperative identification of functional subcortical sites through direct subcortical stimulation; (3) to evaluate the impact of preoperative DTI-FT reconstructions in a neuronavigational setup combined with ISM technique on duration and modalities of surgical procedures, and on functional outcome of the patients. Data are available on 64 patients (52 low-grade and 12 high-grade gliomas). DTI-FT was acquired by a 3-T MR scanner with a single-shot EPI sequence (TR/TE 8986/80 ms, b=1000 s/mm) with gradients applied along 32 non-collinear directions. 3D Fast Field Echo (FFE) T1-weighted imaging (TR/TE 8/4 ms) was performed for anatomic guidance. The corticospinal tract (CST), superior longitudinal, inferior fronto-occipital and uncinatus fasciculi were reconstructed. Data were transferred to the neuronavigational system. Functional subcortical sites identified during ISM were correlated with fiber tracts depicted by DTI-FT. In high-grade gliomas, DTI-FT depicted tracts mostly at the tumor periphery; in low-grade gliomas, fibers were frequently located inside the tumor mass. There was a high correlation between DTI-FT and ISM (sensitivity for CST=95%, language tracts=97%). For a proper reconstruction of the tracts, it was necessary to use a low FA threshold of fiber tracking algorithm and to position additional regions of interest (ROIs). The combination of DTI-FT and ISM decreased the duration of surgery, patient fatigue, and intraoperative seizures. Combination of DTI-FT and ISM allows accurate identification of eloquent fiber tracts and enhances surgical performance and safety maintaining a high rate of functional preservation.

Management of 350 aneurysmal subarachnoid hemorrhages in 22 Italian neurosurgical centers.

OBJECTIVE: To collect information on clinical practice and current management strategies in 22 Italian neurosurgical hospitals for patients with aneurysmal subarachnoid hemorrhage. DESIGN AND SETTING: Observational 6-month study for prospective data collection. PATIENTS: 350 cases of aneurysmal subarachnoid hemorrhage. MEASUREMENTS AND RESULTS: Each center enrolled from 4-36 patients. Neurological deterioration (24%) was more frequent in patients with higher Fisher classification, and with pretreatment rebleeding and it was associated with an unfavorable outcome (46%, 36/78, vs. 33%, 83/251). Aneurysms were mainly secured by clipping (55%, 191/350). An endovascular approach was utilized in 35% (121/350). The more frequent medical complications were fever, recorded in one-half of cases, pneumonia (18%), sodium disturbances (hyponatremia 22%, hypernatremia 17%), cardiopulmonary events as neurogenic pulmonary edema (4%) and myocardial ischemia (5%). Intracranial hypertension was experienced in one-third of the patients, followed by hydrocephalus (29%) and vasospasm (30%). Cerebral ischemia was found in an about one-quarter of the cohort. To identify the independent predictors of outcome we developed a model in which the dichotomized Glasgow Outcome Scale was tested as function of extracranial and intracranial complications. Only high intracranial pressure and deterioration in neurological status were independent factors related to unfavorable outcome. CONCLUSIONS: Our data confirm that in every step of care there is extreme heterogeneity among centers. These patients are complex, with comorbidities, immediate risk of rebleeding, and delayed risk of intracranial and medical complications. Following SAH early treatment and careful intensive care management requires the careful coordination of the various clinical specialties.