Lara Prisco

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.

To wake-up, or not to wake-up: that is the Hamletic neurocritical care question!

The need for a reliable neurological evaluation in severely brain-injured patients conflicts with sedation, which is routinely administered. Helbok and colleagues prospectively evaluated in a small cohort of 20 sedated severely brain-injured patients the effects of a wakeup test on intracranial pressure (ICP), brain tissue oxygen tension and brain metabolism. The test has been considered potentially risky on 34% of the study days. When the test is performed, ICP and cerebral perfusion pressure increase, usually slightly, except in a subgroup of patients with lower cerebral compliance where marked ICP and cerebral perfusion pressure changes were recorded. In this cohort, the information gained with the wake-up test has been negligible. Given the current little knowledge about the benefits of interruption of continuous sedation in brain-injured patients, it is extremely important to adopt multiple monitoring modalities in neurocritical care in order to escape wake-up tests in those patients who will potentially be harmed by this procedure. Once the clinical condition will improve, sedation needs to be tapered and suspended as soon as possible.

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.

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.

Risk of Deep vein thrombosis in neurosurgery: State of the art on prophylaxis protocols and best clinical practices

OBJECTIVE To analytically discuss some protocols in Deep vein thrombosis (DVT)/pulmonary Embolism (PE) prophylaxis currently use in Neurosurgical Departments around the world. DATA SOURCES Analysis of the prophylaxis protocols in the English literature: An analytical and narrative review of literature concerning DVT prophylaxis protocols in Neurosurgery have been conducted by a PubMed search (back to 1978). DATA EXTRACTION 80 abstracts were reviewed, and 74 articles were extracted. DATA ANALYSIS The majority of DVT seems to develop within the first week after a neurosurgical procedure, and a linear correlation between the duration of surgery and DVT occurrence has been highlighted. The incidence of DVT seems greater for cranial (7.7%) than spinal procedures (1.5%). Although intermittent pneumatic compression (IPC) devices provided adequate reduction of DVT/PE in some cranial and combined cranial/spinal series, low-dose subcutaneous unfractionated heparin (UFH) or low molecular-weight heparin (LMWH) further reduced the incidence, not always of DVT, but of PE. Nevertheless, low-dose heparin-based prophylaxis in cranial and spinal series risks minor and major postoperative haemorrhages: 2-4% in cranial series, 3.4% minor and 3.4% major haemorrhages in combined cranial/spinal series, and a 0.7% incidence of major/minor haemorrhages in spinal series. CONCLUSION This analysis showed that currently most of the articles are represented by case series and case reports. As long as clear guidelines will not be defined and universally applied to this diverse group of patients, any prophylaxis for DVT and PE should be tailored to the individual patient with cautious assessment of benefits versus risks.

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.

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.

Evolution of Prophylaxis Protocols for Venous Thromboembolism in Neurosurgery: Results from a Prospective Comparative Study on Low-Molecular-Weight Heparin, Elastic Stockings, and Intermittent Pneumatic Compression Devices

BACKGROUND The incidence of venous thromboembolism (VT) in neurosurgical practice is astonishingly high, representing a major cause of morbidity and mortality. Prophylaxis strategies include elastic stockings, low-molecular-weight heparin (LMWH), and intermittent pneumatic compression (IPC) devices. OBJECTIVE To assess the safety and efficacy of 2 different VT prophylaxis protocols implemented in a European neurosurgical center. METHODS All patients admitted for neurosurgical intervention between 2012 and 2016 were stratified as low, moderate, and high risk of VT and received a combination of elastic stockings and LMWH. The protocol was modified in 2014 with the inclusion of perioperative IPC devices for all patients and only in the high-risk group also postoperatively. RESULTS At time of post-hoc analysis, data obtained from patients included in this study before 2014 (Protocol A, 3169 patients) were compared with those obtained after the introduction of IPC (Protocol B, 3818 patients). Among patients assigned to protocol A, 73 (2.3%) developed deep-vein thrombosis (DVT) and 28 (0.9%) developed pulmonary embolism (PE), 9 of which were fatal (0.3%). Among patients assigned to protocol B, 32 developed DVT (0.8%) and 7 (0.18%) developed PE, with 2 eventually resulting in the death of the patient. A post-hoc analysis confirmed that the use of preoperative LMWH was not associated with a statistically significant greater risk of postoperative bleeding. CONCLUSIONS This study, despite its limitations of the nonrandomized design, seems to suggest that perioperative IPC devices are a non-negligible support in the prophylaxis of clinically symptomatic DVT and PE.