Laura Ganau

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 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.

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.

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.

High Altitude Induced Bilateral Non-Traumatic Subdural Hematoma

BACKGROUND Minor clinical complaints such as headache and drowsiness after a disco party with alcohol abuse may be an unlikely cause for neurological consultation, but, rarely, they may hide a challenging diagnosis. CASE REPORT A young male patient admitted to our Neurosurgical Department for progressive headache showed a sudden clinical deterioration of consciousness; head CT scan was promptly obtained and thick bilateral subdural hematomas requiring urgent craniotomies and drainage were detected. While his anamnesis was surprisingly negative for head trauma, coagulopathies, or other common causes of subdural hematoma, he reported a curious history of 10-d onset of symptoms after a farewell disco party on a high-altitude location, almost 9000 ft (>2700 m) above mean sea level, followed by an intercontinental flight back to his seaside hometown. Following surgery the patient eventually experienced a rapid recovery from this frightening experience. DISCUSSION Due to its uniqueness, the case is reported and the influence of possible provoking causes relevant in the pathogenesis of subdural hematomas is carefully outlined.

Predicting complexity of tumor removal and postoperative outcome in patients with high-grade gliomas

Dear Editor, It was a pleasure to read the article fromMarcus et al. entitled BPredicting surgical outcome in patients with glioblastoma multiforme using pre-operative magnetic resonance imaging: development and preliminary validation of a grading system^ [1]. As the title suggests, the aim of this article was twofold: through an accurate literature review, the authors identified five magnetic resonance imaging (MRI) features previously shown to be predictive of surgical outcomes in patients with glioblastoma multiforme (GBM) and designed a much needed grading system able to objectively quantify the complexity of tumor removal; secondly, they validated this simple and reproducible grading system in their regional referral center for brain tumors, demonstrating that high-complexity lesions are significantly less likely to result in complete resection of the contrast-enhancing lesion than low-complexity GBMs. Although we believe that Marcus et al. deserve praise for such a nicely designed study, and the proposal of a breakthrough descriptive tool for the surgical complexity of GBM, we believe that addressing some methodological and conceptual weaknesses, which are limiting the conclusions drawn in their article, could further improve the usefulness of their grading system. The idea that case complexity in brain tumor surgery is strictly related not only to the extent of resection (EOR) but also to the surgical-related mortality, and morbidity is well known and accepted in the neuroscientific community [2]. Outcomes in neurosurgery are greatly influenced by case complexity, thus the need to fulfill two objectives: (a) preoperatively quantify the risk of brain damage, and (b) minimize them by moving toward the introduction of valid indicators of surgical efficacy. Whereas the grading scale proposed achieved the first objective, it would not be able to offer clinicians with meaningful information in terms of surgical outcomes other than EOR and postoperative complications [3]. The concept of surgical outcome is much larger than this and includes postoperative neurological functional status, progression free survival/overall survival, and quality of life. Such limit was recognized by the authors, who concluded that prospective, multicenter, and larger studies were warranted to address this issue; nonetheless, the grading system proposed seems not equipped to achieve this goal unless coupled with other qualitative and quantitative information of paramount clinical importance. Continuous progresses in basic research allowed to better define the complexity of GBM microenvironment, so that we have now a better understanding of why survival depends on many other factors, including genetic and proteomic profiles of those tumors, their heterogeneous patterns of progression, their intrinsic tolerance mechanisms to immune suppression, and ability to recur locally [4]. Those factors will play an even important role in the future, but are already dictating how patients are investigated preoperatively, which surgical strategies and adjuvant treatment are selected, and most of all the way tailored approaches are offered to our patients [5]. Hence, we thought appropriate to highlight in this letter some reasons for the poor potential of the grading scale by Marcus et al. to predict outcomes. One reason is methodological: almost all studies included in their systematic review to identify features predictive of surgical outcomes were conducted retrospectively and so was their * Mario Ganau mario.ganau@alumni.harvard.edu

Understanding the Pathological Basis of Neurological Diseases Through Diagnostic Platforms Based on Innovations in Biomedical Engineering: New Concepts and Theranostics Perspectives

The pace of advancement of genomics and proteomics together with the recent understanding of the molecular basis behind rare diseases could lead in the near future to significant advances in the diagnosing and treating of many pathological conditions. Innovative diagnostic platforms based on biomedical engineering (microdialysis and proteomics, biochip analysis, non-invasive impedance spectroscopy, etc.) are introduced at a rapid speed in clinical practice: this article primarily aims to highlight how such platforms will advance our understanding of the pathological basis of neurological diseases. An overview of the clinical challenges and regulatory hurdles facing the introduction of such platforms in clinical practice, as well as their potential impact on patient management, will complement the discussion on foreseeable theranostic perspectives. Indeed, the techniques outlined in this article are revolutionizing how we (1) identify biomarkers that better define the diagnostic criteria of any given disease, (2) develop research models, and (3) exploit the externalities coming from innovative pharmacological protocols (i.e., those based on monoclonal antibodies, nanodrugs, etc.) meant to tackle the molecular cascade so far identified.

How Nanotechnology and Biomedical Engineering Are Supporting the Identification of Predictive Biomarkers in Neuro-Oncology

The field of neuro-oncology is rapidly progressing and internalizing many of the recent discoveries coming from research conducted in basic science laboratories worldwide. This systematic review aims to summarize the impact of nanotechnology and biomedical engineering in defining clinically meaningful predictive biomarkers with a potential application in the management of patients with brain tumors. 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: all available basic science and clinical papers relevant to address the above-stated research question were included and analyzed in this study. Based on the results of this systematic review we can conclude that: (1) the advances in nanotechnology and bioengineering are supporting tremendous efforts in optimizing the methods for genomic, epigenomic and proteomic profiling; (2) a successful translational approach is attempting to identify a growing number of biomarkers, some of which appear to be promising candidates in many areas of neuro-oncology; (3) the designing of Randomized Controlled Trials will be warranted to better define the prognostic value of those biomarkers and biosignatures.