Liverana Lauretti

Influence of local environment on the differentiation of neural stem cells engrafted onto the injured spinal cord.

Abstract Objectives: In vitro, neural stem cells (NSCs) proliferate as undifferentiated spheroids and differentiate into neurons, astrocytes and oligodendrocytes. These features make NSCs suitable for spinal cord (SC) reconstruction. However, in vivo experiments have demonstrated that in the injured SC transplanted NSCs either remain undifferentiated or differentiate into the astrocytic phenotype. The microenvironment of the injured SC is believed to play a crucial role in driving the differentiation of the engrafted NSCs. Here, we tested the hypothesis that inflammatory cytokines (ICs) may be involved in the restricted differentiation of NSCs after grafting onto the injured SC. Methods: As the first step, we used immunohistochemistry to analyse the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and interferon (IFN)-γ in the normal SC of mice and following traumatic injury. Then, we investigated whether a combination of TNF-α, IL-1β and IFN-γ may affect the phenotype of murine NSCs in vitro. Results: We found that TNF-α, IL–1β and IFN-γ, which are absent in the normal SC, are all expressed in the injured SC and the expression of these cytokines follows a timely tuned fashion with IFN-γ being detectable as long as 4 weeks after injury. In culture, exposure of proliferating NSCs to a combination of TNF-α, IL–1β and IFN-γ was per se sufficient to induce the astrocytic differentiation of these cells even in the absence of serum. Conclusions: In the traumatically injured SC, differentiation of engrafted NSCs is restricted towards the astrocytic lineage because of the inflammatory environment. ICs are likely to play a major role in differentiation of NSCs in the in vivo conditions.

MICROSCOPIC AND ENDOSCOPIC EXTRACRANIAL APPROACHES TO THE CAVERNOUS SINUS: ANATOMIC STUDY

OBJECTIVE In the past 2 decades, various extracranial approaches to the cavernous sinus (CS), using either microscopic or endoscopic techniques, have been described. The aim of this study was to describe the distinctive anatomic features of these approaches and compare their efficacy in exposing the sella and parasellar areas. METHODS Ten adult cadaver heads with red latex injected in the arterial system were used. Five different approaches were performed: 1) endonasal microscopic transsphenoidal approach; 2) sublabial microscopic transsphenoidal approach, including its variation described by Fraioli et al. (12); 3) transmaxillary microscopic approach; 4) paraseptal endoscopic transsphenoidal approach; and 5) transethmoid-pterygoid-sphenoidal endoscopic approach. The CS exposition was evaluated for each approach and a grading system, which considers surgical maneuverability as well as visualization, was used. RESULTS The medial CS compartment is well exposed with all endoscopic and microscopic transsphenoidal approaches, but it is insufficiently exposed with the transmaxillary approach. The variation to the sublabial microscopic approach suggested by Fraioli et al. allows its widest microsurgical exposure. The lateral compartment is well visualized with the transmaxillary microscopic and the endoscopic approaches. The major anatomic structures that can limit exposure of the CS lateral compartment are the posterior ethmoid and medial pterygoid process. CONCLUSION The sublabial transsphenoidal microscopic approach, with its variations, allows the most versatile extracranial microscopic exposure of the sella and CS. The paraseptal, binostril endoscopic approach allows a very good exposure of the CS; the transethmoid-pterygoid-sphenoidal endoscopic approach achieves the best maneuverability in the lateral compartment of the CS.

Communicating hydrocephalus following surgery and adjuvant radiochemotherapy for glioblastoma

OBJECT Communicating hydrocephalus is an uncommon complication in patients treated for glioblastoma multiforme (GBM). Its pathogenesis remains unclear. The authors evaluated the clinical and radiological factors associated with the onset of communicating hydrocephalus and the impact of ventriculoperitoneal (VP) shunt surgery on the outcome of these patients. METHODS One hundred twenty-four patients harboring GBM, who had undergone craniotomy for tumor resection and adjuvant radiochemotherapy, were retrospectively assessed. Seven of them developed communicating hydrocephalus and were treated with VP shunt surgery. Clinical and radiological estimates included Karnofsky Performance Scale (KPS) score, previous surgery, overall survival (OS), CSF pressure and components, tumor location, and leptomeningeal dissemination. RESULTS All 7 patients who developed communicating hydrocephalus had undergone at least 2 craniotomies for tumor resection before the onset of hydrocephalus (p = 0.0006; Fisher exact test). Six cases showed high levels of CSF proteins. There was a highly significant relationship between ventricular opening at surgery for tumor recurrence and onset of hydrocephalus (p = 0.0002; Fisher exact test). In these patients, VP shunt surgery was followed by a significant improvement of KPS score (p = 0.0180; Wilcoxon signed-rank test). The median OS after VP shunt insertion was 5 ± 2.9 months. CONCLUSIONS Ventricular opening after radiochemotherapy and high CSF protein levels are significant predictors of communicating hydrocephalus in patients with GBM. The VP shunt surgery improves quality of life in these patients.

Acrylic hydrogel implants after spinal cord lesion in the adult rat

Abstract Acrylic hydrogels, like the polymer of 2-hydroxyethyl methacrylate, are biocompatible, mechanically stable, porous materials that can be coated with collagen or laminin acting as bioadhesive substrates. Poly- 2-hydroxyethyl methacrylate sponges have been proposed for restoring the anatomical continuity of damaged neural structures. In the present work, the ability of poly-2-hydroxyethylmethacrylate sponges to provide the injured spinal cord neurons with a conductive substrate for their regenerating axons was investigatedin 32 adultWistar rats. Collagen impregnated poly-2-hydroxyethylmethacrylatesponges were implanted into suction cavities of the dorsal funiculus of the spinal cord. Two to four months after implantation, the spinal cord was removed and processed for histology, and S100 and GFAP immunohistochemistry. To study axonal regeneration into the sponge, the spinal cord or the sensorimotor cortex were injected with 0.05–0.1 ml of an 8% solution of lectin-conjugated horseradish peroxidase or 10% dextran tetramethylrhodamine. The fibroglial reaction, accumulation of mononuclear cells, and angiogenesis at the interface between the spinal cord and the sponge were minimal. Cystic cavitation in the spinal cord was virtually absent. Anterograde labeled axons were seen to penetrate and to elongate the full length of the sponge. These results demonstrate that poly-2-hydroxyethylmethacrylate sponges represent a safe supportive material for regenerating spinal cord axons.

Reconstruction of peripheral nerves: the phenomenon of bilateral reinnervation of muscles originally innervated by unilateral motoneurons.

It is well known that after reconstruction of sectioned peripheral nerves in adult mammals, denervated muscles are reinnervated by the axotomized motoneurons lying in the original motonucleus. It is less well known that these muscles can also be reinnervated by uninjured motoneurons lying in the homologous contralateral motonucleus. Therefore, after nerve reconstruction, bilateral motoneuron reinnervation of muscles can occur. Contralateral motoneurons sprout axons that cross the midline, grow in the reconstructed nerve, and reach muscle targets. This phenomenon was observed after reconstruction of several different peripheral nerves in adult mammals, including the oculomotor nerve in guinea pigs and the facial and sciatic nerves in rats. The retrograde axonal transport of horseradish peroxidase was used for the study of the organization of the brainstem and spinal cord motonuclei. Horseradish peroxidase was injected into the medial rectus muscle, the stylohyoid muscle, and the trunk of the sciatic nerve. The distance between the homologous motonuclei of both sides influenced the occurrence of this phenomenon. In fact, bilateral reinnervation of muscles after nerve reconstruction was found in 36% (sciatic nerve), 50% (facial nerve), and 100% (oculomotor nerve) of the operated animals. The total number of contralateral motoneurons found were 14% (oculomotor nerve), 8% (facial nerve), and 5% (sciatic nerve). Bilateral reinnervation of muscles was evoked by both immediate and delayed peripheral nerve repair and was a stable phenomenon, seen between 3 and 21 months after facial nerve reconstruction.

Quantitative, morphological, and somatotopic nuclear changes after facial nerve regeneration in adult rats: A possible challenge to the “no new neurons” dogma

The anatomic reorganization of the subnucleus that controls the stylohyoid muscle (the stylohyoid subnucleus) within the brain stem facial nucleus was studied after regeneration of the facial nerve in adult rats. Horseradish peroxidase was injected into the right stylohyoid muscle 3 to 21 months after transection and repair of the right facial nerve at the level of the stylomastoid foramen. Position, number, and soma diameter of retrogradely horseradish peroxidase-labeled motoneurons were established, as well as the rostro-caudal extension of the stylohyoid subnucleus. In experimental rats, the stylohyoid subnucleus showed either an ipsilateral (50% of the rats) or a bilateral representation. In all of the experimental rats, the motoneurons composing the stylohyoid subnucleus had a more dispersed horizontal distribution pattern when compared with controls. More than 80% of the motoneurons were located outside the borders of the normal stylohyoid subnucleus, either ventrally or, especially in the rostral sections, dorsally closer to the floor of the fourth ventricle. The mean rostro-caudal length of the stylohyoid subnucleus was 2028.6 +/- 152.7 microns. The mean motoneuron number was 481.4 +/- 109.5 (2.20-fold greater than control values), and the motoneuron diameter distribution ranged from 7 to 43 microns. This study demonstrates that after regeneration of the facial nerve in adult rats, major changes occur in both the location and number of motoneurons that make up the stylohyoid subnucleus.(ABSTRACT TRUNCATED AT 250 WORDS)

Olfactory groove meningioma: report of 99 cases surgically treated at the Catholic University School of Medicine, Rome.

OBJECTIVE We reviewed our series of olfactory groove meningiomas (OGMs) with the aim to relate the surgical approach with outcome and to define clinical and pathologic predictors of prognosis. METHODS Ninety-nine patients who underwent 113 craniotomies at our Institution between 1984 and 2010 were entered this study. The relationship between surgical approach (bifrontal, fronto-orbito-basal, and pterional) and either tumor diameter, extent of tumor resection, complication rate, need of reoperation, and Karnofsky Performance Status (KPS) was analyzed. The impact of age (≤ 70 vs. > 70 years), sex, tumor diameter (< 6 vs. ≥ 6 cm), pre- and postoperative KPS (< 80 vs. ≥ 80), Simpson grade (I-II vs. III-IV), and World Health Organization (WHO) histologic grade (I vs. II-III) on survival was assessed. Kaplan-Meier survival curves were plotted and differences in survival between groups of patients were compared. A multivariate analysis adjusted for age, pre- and postoperative KPS, Simpson grade, tumor diameter, and WHO histologic grade also was performed. RESULTS The fronto-orbito-basal approach (n = 22) allowed a significantly greater percentage of Simpson I-II removals than the bifrontal (n = 70) and pterional approach (n = 21) (P = 0.0354 and P = 0.0485, respectively). The risk of life-threatening complications trended to be lower in patients operated upon either via the fronto-orbito-basal and via the pterional approach than in those treated via the bifrontal approach. Retraction-related brain swelling did not occur in any case after the fronto-orbito-basal approach (P = 0.0384); however, this approach was associated with a greater rate of cerebrospinal fluid leak (P = 0.0011). Among prognostic factors, age ≤ 70 years (P = 0.0044), tumor diameter <6 cm (P = 0.0455), pre- and postoperative KPS ≥ 80 (both P < 0.0001), Simpson grade I-II (P = 0.0096), and WHO histologic grade I (P = 0.0112) were significantly associated with longer overall survival. Age (P = 0.0393) and WHO histologic grade (P = 0.0418) emerged as independent prognostic factors for overall survival on multivariate analysis. CONCLUSION In the largest series of OGMs published to date, the bifrontal approach was associated with a greater risk of life-threatening complications compared with the lateral pterional and fronto-orbito-basal approaches. The fronto-orbito-basal approach provided greater chances of total tumor removal than the bifrontal and pterional approaches. Two independent factors for overall survival of patients with OGM were identified, namely age and WHO grade.

Long survival in an untreated solitary choroid plexus metastasis from renal cell carcinoma: case report and review of the literature

Brain metastases from renal cell carcinoma (RCC) are rare. Among them, the metastases localized only in the choroid plexus are exceptional and only six cases are reported in the literature. Here we report on a patient with a single choroid plexus metastasis from RCC which presented an unusual biological behaviour. For several years, such metastasis was interpreted as a benign intraventricular tumor and was not treated. Four years after the initial neuroradiological evidence, because of the appearance of symptoms, the brain metastasis was excised. We think that this unusual biological behaviour of the tumor determined the late inset of the neurological symptoms, despite the location at the choroid plexus that usually leads to an early obstructive hydrocephalus. To our knowledge, this 46months survival is the longest survival of a patient affected by a single choroid plexus metastasis from RCC.

Original ArticlesNeurosurgery of the Peripheral Nervous System:: Cubital Tunnel Syndrome

Cubital tunnel syndrome (CUTS), the entrapment of the ulnar nerve at the elbow, is the second most common compressive neuropathy after carpal tunnel syndrome. CUTS represents a major disability in the work force, especially since the increased use of computers and the accompanying repetitive use of the upper limb with the elbow in a fixed position. However, many cases of CUTS are still idiopathic.

Effects of levo-acetylcarnitine on second motoneuron survival after axotomy

Little is known about factors that regulate the survival of cranial motoneurons which project to peripheral targets. Various neurotrophic factors of central and peripheral origin have been isolated. In this study, we examined thirteen newborn Wistar rats to determine the effects of acetyl-L-carnitine treatment on the survival of motoneurons within the facial nucleus after transection of the facial nerve. Acetyl-L-carnitine was administered for 7 days in seven rats after nerve transection, while saline solution was injected in 6 rats used as controls. Both the motoneuron number and the motoneuron diameter were significantly higher in the facial nucleus of the rats treated with acetyl-L-carnitine than in the facial nucleus of the control rats. The results obtained suggest that acetyl-L-carnitine can rescue a substantial number of facial motoneurons from axotomy-induced cell death. Compared to neurotrophic factors, because of its simple molecular structure, acetyl-L-carnitine permits a safe oral and parenteral administration. It is suggested that acetyl-L-carnitine could be considered for use as a therapeutic agent in neurodegenerative disorders.