Mario Ganau

Autologous fibrin sealant (Vivostat(®)) in the neurosurgical practice: Part I: Intracranial surgical procedure.

Background: Hemorrhages, cerebrospinal fluid (CSF) fistula and infections are the most challenging postoperative complications in Neurosurgery. In this study, we report our preliminary results using a fully autologous fibrin sealant agent, the Vivostat® system, in achieving hemostasis and CSF leakage repair during cranio-cerebral procedures. Methods: From January 2012 to March 2014, 77 patients were studied prospectively and data were collected and analyzed. Autologous fibrin sealant, taken from patients blood, was prepared with the Vivostat® system and applied on the resection bed or above the dura mater to achieve hemostasis and dural sealing. The surgical technique, time to bleeding control and associated complications were recorded. Results: A total of 79 neurosurgical procedures have been performed on 77 patients. In the majority of cases (98%) the same autologous fibrin glue provided rapid hemostasis and dural sealing. No patient developed allergic reactions or systemic complications in association with its application. There were no cases of cerebral hematoma, swelling, infection, or epileptic seizures after surgery whether in the immediate or in late period follow-up. Conclusions: In this preliminary study, the easy and direct application of autologous fibrin sealant agent helped in controlling cerebral bleeding and in providing prompt and efficient dural sealing with resolution of CSF leaks. Although the use of autologous fibrin glue seems to be safe, easy, and effective, further investigations are strongly recommended to quantify real advantages and potential limitations.

A DNA-based nano-immunoassay for the label-free detection of glial fibrillary acidic protein in multicell lysates

UNLABELLED We have developed a quantitative approach to eventually enable precise and multiplexing protein analysis of very small systems, down to a single or a few cells. Through DNA-directed immobilization of DNA-protein conjugates we immobilized antibodies specific for a certain protein of interest, on a complementary DNA nanoarray fabricated by means of nanografting, a nanolithography technique based on atomic force microscopy (AFM). The proof of concept was realized for glial fibrillary acidic protein (GFAP), a biomarker crucial in cells differentiation of astrocytes, and functional to grade classification of gliomas, the most common of primary malignant brain tumors. The efficiency of the nano-immuno sensing was tested by obtaining the immobilization of purified recombinant GFAP protein at different concentration in a standard solution then in a cellular lysate. A comparison of sensitivity between our technique and conventional ELISA assays is provided at the end of the paper. FROM THE CLINICAL EDITOR This team developed a quantitative approach to enable precise and multiplexing protein analysis of very small systems, down to a single or a few cells, demonstrating the utility of this DNA-based nano-immunoassay in the detection of GFAP.

Challenging New Targets for CNS–HIV Infection

The central nervous system (CNS) represents an important target for HIV infection during multiple stages of the disease: early, after invasion of the host, acting as a viral reservoir; lately, subverting its function and causing peripheral neuropathies and neurocognitive disorders; and lastly, during the final stage of NeuroAIDS, triggering opportunistic infections, cancers, and dementia. Highly active antiretroviral therapy, a combination of drugs that inhibits enzymes essential for HIV replication, can reduce the viremia and the onset of opportunistic infections in most patients, and prolong the survival. Among the limits of the current treatments the most noticeable is the inability to eradicate HIV-infected cells, both, limiting the time frame in which antiretroviral therapies initiated after exposure to HIV can prevent infection, and allowing replication-competent virus that persists in infected cells to emerge rapidly after the cessation of treatments. Many strategies are currently under evaluation to improve HIV treatment, unfortunately more than 98% of drug candidates for CNS disorders never make it to the clinic; here in we report how nanoformulated strategies might be adapted and applied to the field of CNS–HIV infection.

Postoperative aseptic intracranial granuloma: the possible influence of fluid hemostatics.

Background. Numerous reports have demonstrated how postoperative intracranial granulomas can often mimic neoplasm clinically, radiologically, and even macroscopically. Herein we present an unusual case of postsurgical intracranial aseptic granuloma secondary to a chronic inflammatory reaction without any identifiable retained foreign body. Case Description. A 71-year-old patient started complaining of severe headache seven months after surgical excision of WHO Grade I right frontal falx meningioma. CT and MRI scans disclosed a contrast-enhanced lesion with diffuse mass effect in the previous surgical site. The lesion was resected; intraoperative finding and histological specimens led to the diagnosis of postoperative granuloma, likely expression of a glial reaction to the fluid absorbable hemostatics applied in the surgical site after meningioma excision. The possible granuloma-inducing materials and the timing of granuloma formation are discussed. Conclusion. A comprehensive analysis of clinical and neuroradiological data, as well as results of blood tests including positive and negative acute phase proteins, is mandatory to raise the suspicion of postoperative granuloma. The treatment options should be evaluated on a case-by-case basis, with a conservative attitude being the one of choice only for patients without progressive neurological deficit. Alternatively, aggressive surgical treatment and histopathological examination should be advocated.

Postoperative granulomas versus tumor recurrence: PET and SPET scans as strategic adjuvant tools to conventional neuroradiology

A mandatory differential diagnosis between postoperative granulomas and tumor recurrence is required whenever space-occupying lesions are detected at the surgical site, few months after removal of the intracranial neoplasm, because these two pathologies can often mimic each other clinically, by imaging techniques and even macroscopically. Since history or signs of inflammation may be lacking, and neurological complaints are generally nonspecific, a thorough imaging investigation is usually the only way to diagnosis. Herein we discuss the pathological basis and timing of granuloma formation along with the imaging characteristics and nuclear medicine findings necessary to confirm or exclude the diagnosis of tumor recurrence. In conclusion, the high sensitivity of positron emission tomography and the wide availability of single photon emission tomography can identify certain parameters (isometabolism, uptake in macrophages, etc.) to support differential diagnosis between postoperative granulomas and tumor recurrence.

Trigeminal neuralgia: successful antiepileptic drug combination therapy in three refractory cases.

Antiepileptic drug combination therapy remains an empirical second-line treatment approach in trigeminal neuralgia, after treatment with one antiepileptic drug or other nonantiepileptic drugs have failed. The results in three patients followed in our clinic are not sufficient to draw definitive conclusions, but suggest the possibility of developing this type of therapeutic approach further.

Clinical and radiological aspects of cerebellopontine neurinoma presenting with recurrent spontaneous bleedings.

Background: Neurinomas are benign, usually encapsulated, tumors growing in peripheral nerve sheath with a high incidence in the cerebellopontine angle. Case Description: We report a case of vestibular neurinoma (VN) with a “biphasic” pattern of intratumoral hemorrhage presenting with cephalalgia along with progressive ipsilateral mild impairment of both VII and VIII cranial nerves. A thorough preoperative magnetic resonance imaging study better characterized the patchy pattern of the round shaped lesion, resulting in three different intensity signals, due to the peculiar characteristics of the tumoral mass and the recurrent bleedings, respectively. Postoperatively, histological examination confirmed the diagnosis of neurinoma. Conclusion: Hemorrhagic VN are rare tumors; from the first case described in 1974 only 43 more have been reported in the literature so far. Noteworthy, “biphasic” bleedings are even rarer. From an accurate review of the literature we collected and thus emphasized the radiological and clinical features of this rare entity. Eventually, we suggest that the early surgical removal of clots and tumor is essential to provide the best chance of neurological improvement.

Current and Future Applications of Biomedical Engineering for Proteomic Profiling: Predictive Biomarkers in Neuro-Traumatology

This systematic review aims to summarize the impact of nanotechnology and biomedical engineering in defining clinically meaningful predictive biomarkers in patients with traumatic brain injury (TBI), a critical worldwide health problem with an estimated 10 billion people affected annually worldwide. Data were collected through a review of the existing English literature performed on Scopus, MEDLINE, MEDLINE in Process, EMBASE, and/or Cochrane Central Register of Controlled Trials. Only experimental articles revolving around the management of TBI, in which the role of new devices based on innovative discoveries coming from the field of nanotechnology and biomedical engineering were highlighted, have been included and analyzed in this study. Based on theresults gathered from this research on innovative methods for genomics, epigenomics, and proteomics, their future application in this field seems promising. Despite the outstanding technical challenges of identifying reliable biosignatures for TBI and the mixed nature of studies herein described (single cells proteomics, biofilms, sensors, etc.), the clinical implementation of those discoveries will allow us to gain confidence in the use of advanced neuromonitoring modalities with a potential dramatic improvement in the management of those patients.

Complex developmental abnormality of the atlas mimicking a Jefferson fracture: Diagnostic tips and tricks

Congenital atlas abnormalities are rare — often asymptomatic — findings, not requiring any specific treatment. They are frequently discovered, by chance, in trauma patients, in the course of the radiological work flow at the Emergency Department. In these cases they may represent a diagnostic challenge, since physicians are expected to differentiate them from complex C1 fractures (isolated Jeffersons fractures or associated with Anderson and d‘Alonzos fractures) requiring surgical treatment. Although difficult to identify, a correct diagnosis is mandatory in order to optimize the patients treatment. In this article we report a case of congenital atlas abnormality, and discuss the tips and tricks to make a correct differential diagnosis through the most appropriate clinical and radiological work flow.

Dealing with the Surgical and Medical Challenges of Penetrating Brain Injuries

Peacetime has reduced the overall incidence of penetrating brain injuries (PBI), and those related to missile penetration are not common anymore at least in western countries. Nevertheless, PBI still occur, and car crashes or work accidents are their main causes. The management of such cases is characterized by many challenges, not only from a surgical and medical point of view, but also for the different and sometimes bizarre dynamics by which they present. Herein we report an unusual deep penetrating brain injury, due to a high-energy crash against a metallic rod in a construction site, with a good surgical outcome despite dramatic clinical conditions on admission. A discussion of the surgical results and functional outcome related to PBI, as found in the English medical literature, is provided. Moreover the most common postoperative complications along with the diagnostic flow charts and therapeutic options useful to prevent inappropriate treatment are highlighted.