Marco Fontanella

Neuropsychological assessment after microsurgical clipping or endovascular treatment for anterior communicating artery aneurysm

Summary¶Background. After open surgery for ruptured ACoA aneurysms, several patients who have achieved a favourable neurological outcome still exhibit significant cognitive deficits. The aim of this study was to investigate the cognitive performances in patients with ACoA aneurysms submitted to different therapeutic options such as endovascular treatment and surgical clipping. Methods. We evaluated 37 consecutive patients in WFNS grade I or II, who underwent an early treatment (within 48 hours) of a bleeding ACoA aneurysm: 20 out of 37 were surgically clipped (group A) and 17 were treated with endovascular coiling (group B).These two groups were compared with 16 patients (group C) with subarachnoid haemorrhage and negative cerebral panangiography and with 18 volunteers (group D) without neurological or psychiatric disorders.All patients were neurologically intact at discharge and were in Glasgow Outcome Scale 1 at 6 months follow-up after SAH.All subjects were tested to assess selective attention, verbal, spatial and logical memory, frontal lobe executive functions, language and intelligence. Depressive symptoms and anxiety were also examined. Findings. Selective attention, verbal and spatial memory, and intelligence tests didn’t show any significant difference between the patients and the controls.Surgically treated patients showed a significant worse performance on the logical memory and on the frontal lobe executive functions compared to controls, while the endovascular group and the group C (not treated) showed a significant decrease only in the literal fluency score.Moreover, the surgical group showed a significant impairment in using grammatical and syntactical rules to produce sentences. No significant difference was found between the group B, C and controls. Treated patients were not significantly more depressive or anxious than controls. Interpretation. Investigation of neuropsychological deficits can show an impairment, even in patients classified as good outcome by Glasgow Outcome Scale (GOS).The frontal lobe functions and language are impaired especially in surgically treated in comparison with controls, but no significant difference was found respect to the endovascular and no treated patients (group C).

Recent therapeutic strategies for spinal cord injury treatment: possible role of stem cells

Spinal cord injury (SCI) often results in significant dysfunction and disability. A series of treatments have been proposed to prevent and overcome the formation of the glial scar and inhibitory factors to axon regrowth. In the last decade, cell therapy has emerged as a new tool for several diseases of the nervous system. Stem cells act as minipumps providing trophic and immunomodulatory factors to enhance axonal growth, to modulate the environment, and to reduce neuroinflammation. This capability can be boosted by genetical manipulation to deliver trophic molecules. Different types of stem cells have been tested, according to their properties and the therapeutic aims. They differ from each other for origin, developmental stage, stage of differentiation, and fate lineage. Related to this, stem cells differentiating into neurons could be used for cell replacement, even though the feasibility that stem cells after transplantation in the adult lesioned spinal cord can differentiate into neurons, integrate within neural circuits, and emit axons reaching the muscle is quite remote. The timing of cell therapy has been variable, and may be summarized in the acute and chronic phases of disease, when stem cells interact with a completely different environment. Even though further experimental studies are needed to elucidate the mechanisms of action, the therapeutic, and the side effects of cell therapy, several clinical protocols have been tested or are under trial. Here, we report the state-of-the-art of cell therapy in SCI, in terms of feasibility, outcome, and side effects.

Fluorescence and image guided resection in high grade glioma

The extent of resection in high grade glioma is increasingly been shown to positively effect survival. Nevertheless, heterogeneity and migratory behavior of glioma cells make gross total resection very challenging. Several techniques were used in order to improve the detection of residual tumor. Aim of this study was to analyze advantages and limitations of fluorescence and image guided resection. A multicentric prospective study was designed to evaluate the accuracy of each method. Furthermore, the role of 5-aminolevulinc acid and neuronavigation were reviewed. Twenty-three patients harboring suspected high grade glioma, amenable to complete resection, were enrolled. Fluorescence and image guides were used to perform surgery. Multiple samples were obtained from the resection cavity of each lesion according to 5-ALA staining positivity and boundaries as delineated by neuronavigation. All samples were analyzed by a pathologist blinded to the intra-operative labeling. Decision-making based on fluorescence showed a sensitivity of 91.1% and a specificity of 89.4% (p<0.001). On the other hand, the image-guided resection accuracy was low (sensitivity: 57.8%; specificity: 57.4%; p=0.346). We observed that the sensitivity of 5-ALA can be improved by the combined use of neuronavigation, but this leads to a significant reduction in specificity. Thus, the use of auxiliary techniques should always be subject to critical skills of the surgeon. We advocate a large-scale study to further improve the assessment of multimodal approaches.

Mesenchymal Stem Cell Transplantation Reduces Glial Cyst and Improves Functional Outcome After Spinal Cord Compression

BACKGROUND Mesenchymal stem cells (MSCs) are multipotent stem cells that have a supportive role in regenerative therapies, especially in the central nervous system, where spontaneous regeneration is limited. MSCs can exert a paracrine activity and modulate the inflammatory response after a central nervous system injury. Spinal cord injury (SCI) leads to permanent neurologic deficits below the injury site, owing to neuronal and axonal damage. Among experimental treatments after SCI, cell transplantation has emerged as a promising approach. METHODS Using a compression injury model in the mouse spinal cord, MSCs were acutely transplanted into the lesion cavity; injured mice without the graft served as controls. After 26 days, the survival of MSCs was investigated, and their effect on the formation of glial cyst and on injury-related inflammation was evaluated. RESULTS Grafted MSCs remained permanently undifferentiated. The lesion volume was reduced by 31.6% compared with control mice despite the fact that astroglial and microglial activation was not altered by the graft. Sensory and motor tests showed that MSC cell therapy results in improvement on a battery of behavioral tests compared with control mice: MSC-treated mice versus control mice scored 0.00 versus 0.50 in the posture test, 0.00 versus 1.50 in the hindlimb flexion test, 3.00 versus 2.25 in the sensory test, and 7.50 mistakes versus 15.83 mistakes in the foot-fault test. CONCLUSIONS These results underscore the therapeutic potential of MSCs, making them promising treatments for central nervous system pathologies.

False-negative angiograms in subarachnoid haemorrhage due to intracranial aneurysms

Abstract Of 440 patients with spontaneous subarachnoid haemorrhage in whom an aneurysm was suspected, 60 had a negative angiogram. A second angiogram performed 1–4 weeks later revealed an aneurysm in 5 of 40 cases. Of these patients, 3 had a second haemorrhage. In all cases, diffuse bleeding, with involvement of the anteroinferior interhemispheric fissure, was present on CT. There were three aneurysms of the anterior communicating artery and two of the carotid siphon. The reasons for the false-negative angiograms and the usefulness of repeated angiography are discussed.

Use of "custom made" porous hydroxyapatite implants for cranioplasty: postoperative analysis of complications in 1549 patients.

Background: Cranioplasty is a surgical intervention aimed at reestablishing the integrity of skull defects, and should be considered the conclusion of a surgical act that began with bone flap removal. Autologous bone is still considered the treatment of choice for cranioplasty. An alternative choice is bioceramic porous hydroxyapatite (HA) as it is one of the materials that meets and comes closest to the biomimetic characteristics of bone. Methods: The authors analyzed the clinical charts, compiled by the neurosurgeon, of all patients treated with custom-made porous HA devices (Custom Bone Service Fin-Ceramica, Faenza) from which epidemiological and pathological data as well as material-related complications were extrapolated. Results: From November 1997 to December 2010, 1549 patients underwent cranioplasty with the implantation of 1608 custom-made porous HA devices. HA was used in 53.8% of patients for decompressive craniectomy after trauma or intracranial hemorrhage, while the remaining cases were for treated for comminuted fracture, cutaneous or osseous resection, cranial malformation, autologous bone reabsorption or infection or rejection of previously implanted material. The incidence of adverse events in patients treated for cranioplasty, as first line treatment was 4.78% (56 events/1171 patients), and 5.02%, (19 events/378 patients) at second line. Conclusion: This study demonstrates that HA is a safe and effective material, is well tolerated in both adult and pediatric patients, and meets the requirements necessary to repair craniolacunia.

Embryonic and adult stem cells promote raphespinal axon outgrowth and improve functional outcome following spinal hemisection in mice

Spinal cord injury (SCI) often results in permanent neurological deficits below the injury site. Serotonergic raphespinal projections promote functional recovery after SCI, but spontaneous regeneration of most severed axons is limited by the glial cyst and scar that form at the lesion site. Stem cell (SC) transplantation offers a promising approach for inducing regeneration through the damaged area. Here we compare the effects of transplantation of embryonic neural precursors (NPs) or adult mesenchymal SCs, both of which are potential candidates for SC therapy. The spinal cord was hemisected at the L2 neuromer in adult mice. Two weeks post‐injury, we transplanted neural precursors or mesenchymal SCs into the cord, caudal to the hemisection. Injured mice without a graft served as controls. Mice were tested for functional recovery on a battery of motor tasks, then killed and analysed for survival of grafted cells, for effects of engraftment on the local cellular environment and for the sprouting of serotonergic axons. Both types of SCs survived and were integrated into the host tissue, but only the NPs expressed neuronal markers. All transplanted animals displayed an increased number of serotonin‐positive fibres caudal to the hemisection, compared with untreated mice. And both cell types led to improved motor performance. These results point to a therapeutic potential for such cell grafting.

TUMOR NECROSIS FACTOR-α GENE AND CEREBRAL ANEURYSMS

OBJECTIVEThe pathogenesis of intracranial aneurysms is still uncertain. In addition to atherosclerosis, immunological factors may play a role in the disease. Recent studies have suggested that tumor necrosis factor-α (TNF-α), one of the main proinflammatory cytokines, may play a key role in the formation and rupture of cerebral aneurysms. The purpose of this study is to evaluate the association of a functionally active polymorphism (−308 G<A) in the TNF-α gene with the risk and the clinical features of aneurysmal subarachnoid hemorrhage. METHODSA total of 171 consecutive aneurysmal subarachnoid hemorrhage patients and 144 healthy controls were involved in the study. Computed tomographic scan findings were assessed by Fisher grade; clinical neurological assessment was performed using the Hunt and Hess grading system. Patients and controls were genotyped for the−308 biallelic (G<A) polymorphism of the TNF-α gene. RESULTSThe TNF-α G allele was significantly more frequent in patients than in controls (χ2 = 5.59; P = 0.0181) and homozygosity for the G allele, compared with remaining genotypes, was associated with a significantly increased risk of aneurysmal subarachnoid hemorrhage (odds ratio = 2.20; 95% confidence interval = 1.29<odds ratio<3.75). Allelic and genotypic frequencies of the examined polymorphism were not significantly different in disease subgroups. The different TNF-α genotypes do not seem to significantly modify the main clinical features of the disease. CONCLUSIONOur data suggests that the TNF-α gene or a linked locus significantly modulates the risk for aneurysmal subarachnoid hemorrhage. Additional studies in different populations are warranted to confirm our findings.

Periprocedural morbidity and mortality by endovascular treatment of cerebral aneurysms with GDC: a retrospective 12-year experience of a single center.

Despite increasing experience and improved material, endovascular treatment of cerebral aneurysms still has risks linked to the technique itself and to the specificity of the pathology treated. The purpose of this report is to examine procedural technical and clinical negative events, even minimal ones, occurring in this type of treatment. We considered 557 procedures carried out from January 1994 to December 2005 in 533 patients harboring 550 aneurysms. Of the patients, 448 presented with SAH and 85 with unruptured aneurysms. All procedures were performed under general anesthesia. The GDC-10 system was routinely used. Additional devices like the balloon remodeling technique, Trispan and stents were also occasionally used. Every procedural complication occurring during or soon after treatment was registered. Endovascular treatment was completed in 539 out of 557 procedures. There were 18 failures (3.3%). Occlusion of the aneurysm was judged complete in 343 (64%), near complete in 184 (34%) and incomplete in 12 (2%). Procedural complications occurred in 72 (13%) of the cases. The most frequent negative events were thromboembolisms (6.6%) and ruptures (3.9%). Other types (coil migration, transient occlusions of the parent vessel, dissections and early rebleeding) were rarer (2.5%). In the majority of cases there were no clinical consequences. Procedural morbidity and mortality were 1.1 and 1.8%, respectively. Considering the 449 procedures performed in ruptured and the 90 in the unruptured aneurysms separately, morbidity and mortality were 1.1 and 2.2% in the former group and 1.1 and 0% in the latter. Many factors influence the risk of complications. Being progressively aware of this and with increasing experience, the frequency can be limited. Negative events linked to the procedure have more significant serious clinical consequences in patients admitted in a critical clinical condition after SAH, because of the already present changes involving the brain parenchyma and cerebral circulation.

Cystic versus solid vestibular schwannomas: a series of 80 grade III–IV patients

Cystic acoustic neuromas are less frequent than solid ones and present different clinical and radiological features. Cystic schwannomas are larger, show a shorter clinical history and a different risk of postoperative complications. This study was designed to compare surgical results and complications of solid and cystic vestibular schwannomas of matching size operated upon via either a retrosygmoid or a translabyrinthine approach. The study included 80 patients presenting with grade III and IV acoustic vestibular schwannomas referred to the Neurosurgical and ENT team in the Department of Neuroscience of Torino, Italy. Twenty-six were cystic and 54 were solid tumours. Clinical history, surgical results and complications were compared between the two groups. In cystic tumors, rapid clinical worsening is common, due to sudden expansion of cystic elements. Tighter adherences are found between cystic tumours and nervous elements (particularly brainstem and possibly facial nerve), once compared to solid ones. Operative morbidity appears to be higher in cystic tumours. A wait and see policy should not to be applied to patients with cystic tumours. Careful technique, possibly sharp dissection, to divide the tumour adherences from the nervous tissue must be employed, in order to avoid lesions on brainstem veins and traction on a thin facial nerve. Severe complications may be caused by the excessive efforts to dissect brainstem adherences.