Alessandro Ducati

High tidal volume is associated with the development of acute lung injury after severe brain injury : An international observational study

Objective:Although a significant number of patients with severe brain injury develop acute lung injury, only intracranial risk factors have previously been studied. We investigated the role of extracranial predisposing factors, including hemodynamic and ventilatory management, as independent predictors of acute lung injury in brain-injured patients. Design:Prospective multicenter observational study. Setting:Four European intensive care units in university-affiliated hospitals. Patients:Eighty-six severely brain-injured patients enrolled in 13 months. Interventions:None. Measurements and Main Results:All patients with severe brain injury (Glasgow Coma Scale score <9) were studied for 8 days from admission. Ventilatory pattern, respiratory system compliance, blood gas analysis, and hemodynamic profile were recorded and entered in a stepwise regression model. Length of stay in the intensive care unit, ventilator-free days, and mortality were collected. Eighteen patients (22%) developed acute lung injury on day 2.8 ± 1. They were initially ventilated with significantly higher tidal volume per predicted body weight (9.5 ± 1 vs. 10.4 ± 1.1), respiratory rate, and minute ventilation and more often required vasoactive drugs (p < .05). In addition to a lower Pao2/Fio2 (odds ratio 0.98, 95% confidence interval 0.98–0.99), the use of high tidal volume (odds ratio 5.4, 95% confidence interval 1.54–19.24) and relatively high respiratory rate (odds ratio 1.8, 95% confidence interval 1.13–2.86) were independent predictors of acute lung injury (p < .01). After the onset of acute lung injury, patients remained ventilated with similar tidal volumes to maintain mild hypocapnia and had a longer length of stay in the intensive care unit and fewer ventilator-free days (p < .05). Conclusions:In addition to a lower Pao2/Fio2, the use of high tidal volume and high respiratory rate are independent predictors of acute lung injury in patients with severe brain injury. In this patient population, alternative ventilator strategies should be considered to protect the lung and guarantee a tight CO2 control.

Neuronal and glial localization of GAT-1, a high-affinity gamma-aminobutyric acid plasma membrane transporter, in human cerebral cortex: with a note on its distribution in monkey cortex

High‐affinity γ‐aminobutyric (GABA) plasma membrane transporters (GATs) influence the action of GABA, the main inhibitory neurotransmitter in the human cerebral cortex. In this study, the cellular expression of GAT‐1, the main cortical GABA transporter, was investigated in the human cerebral cortex by using immunocytochemistry with affinity‐purified polyclonal antibodies directed to the C‐terminus of rat GAT‐1.

Anterior cervical fusion with polyetheretherketone (PEEK) cages in the treatment of degenerative disc disease. Preliminary observations in 36 consecutive cases with a minimum 12-month follow-up

SummaryStudy design. Retrospective analysis of 36 cases of degenerative disc disease treated by interbody fusion with polyetheretherketone (PEEK) cages.Objective. To determine the safety and efficiency of PEEK cages for anterior cervical fusion (ACF).Summary of background data. ACF with autologous bone has been reported since over 50 years ago. The recent development of cages housing materials inducing osteogenesis simplifies the technique of interbody fusion. The main purposes of bone substitutes for ACF are immediate biomechanical support, osteo-integration of the graft, and elimination of local side effects at the donor site. This report shows our results using PEEK cages.Materials and methods. During an 18-month period, 36 consecutive patients had cervical fusions at 43 levels between C3 and C7. All operations involved one or two disc spaces for degenerative disc disease. We implanted all disc spaces with PEEK cages (Stryker Corporation, Kalamazoo, MI) containing granulated coralline hydroxylapatite (Pro-Osteon 200, Interpore Cross International, Irvine, CA) or deantigenated pig bone in a gel solution (Gen-Os, Tecnoss, Torino, Italy).Results. About 97% of patients had a good to excellent outcome; the result in one myelopathic patient was fair. The cervical fusion rate was 16.7% at 3 months, 61.1% at 6 months, and 100% at one year.Conclusions. PEEK cages appear to be safe and efficient for ACF. In order to confirm our preliminary impressions studies on larger series with long term follow-up are warranted.

Motor and Nonmotor Symptom Follow-Up in Parkinsonian Patients after Deep Brain Stimulation of the Subthalamic Nucleus

Objective: To evaluate motor and nonmotor symptoms in patients with Parkinson’s disease undergoing bilateral deep brain stimulation of the subthalamic nucleus (STN DBS). Methods: Thirty-six consecutive patients receiving bilateral STN stimulation implants were evaluated preoperatively as well as 12 and 24 months after surgery. Motor symptoms were assessed through the Unified Parkinson’s Disease Rating Scale (UPDRS). Data concerning nonmotor symptoms were collected from items of the UPDRS and 2 additional questions from clinical charts regarding constipation and urological dysfunction. Results: STN DBS was effective in controlling motor symptoms; concerning nonmotor symptoms, sleep quality and constipation improved after surgery as compared to baseline. Salivation, swallowing and sensory complaints were ameliorated to a comparable degree by the medication on state, whether preoperatively or postoperatively. With a lower dose of dopaminergic medication, however, the medication on state appeared to be a much larger percentage of the day postoperatively. No significant variations were detected in intellectual impairment, depression, thought disorders, motivation, falling unrelated to freezing, nausea, orthostatic hypotension and urological dysfunction. Conclusions: STN DBS effectively controls motor symptoms, while nonmotor features of advanced Parkinson’s disease patients are mostly unchanged after surgery, even though some specific aspects, notably sleep complaints and constipation, are ameliorated.

Electrophysiological properties of thalamic, subthalamic and nigral neurons during the anti‐parkinsonian placebo response

Placebo administration to Parkinson patients is known to induce dopamine release in the striatum and to affect the activity of subthalamic nucleus (STN) neurons. By using intraoperative single‐neuron recording techniques in awake patients, here we extend our previous study on STN recording, and characterize part of the neuronal circuit which is affected by placebos. In those patients who showed a clinical placebo response, there was a decrease in firing rate in STN neurons that was associated with a decrease in the substantia nigra pars reticulata (SNr) and an increase in the ventral anterior (VA) and anterior ventral lateral (VLa) thalamus. These data show that placebo decreases STN and SNr activity whereas it increases VA/VLa activity. By contrast, placebo non‐responders showed either a lack of changes in this circuit or partial changes in the STN only. Thus, changes in activity in the whole basal ganglia–VA/VLa circuit appear to be important in order to observe a clinical placebo improvement, although the involvement of other circuits, such as the direct pathway bypassing the STN, cannot be ruled out. The circuit we describe in the present study is likely to be a part of a more complex circuitry, including the striatum and the internal globus pallidus (GPi), that is modified by placebo administration. These findings indicate that a placebo treatment, which is basically characterized by verbal suggestions of benefit, can reverse the malfunction of a complex neuronal circuit, although these placebo‐associated neuronal changes are short‐lasting and occur only in some patients but not in others.

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.

Solid lipid nanoparticles: could they help to improve the efficacy of pharmacologic treatments for brain tumors?

Abstract Objectives: Brain malignant neoplasms are still characterized by poor prognosis due to their peculiar hallmarks that severely limit aggressive multimodal therapeutic approaches. The optimization of the intratumoral drug delivery, directed to achieve effective concentrations and to reduce systemic undesired toxicity, is one of the primary goals of the brain tumors therapeutic strategies. Different passive and active delivery carriers allowing to a better control of drug distribution, metabolism, and elimination after parenteral administration have been developed. In the present review we will describe general characteristics and evaluate the efficacy of Solid Lipid Nanoparticles (SLN) as carriers of different drugs in experimental brain malignant tumor therapy. Methods: SLN vehiculating different illustrative types of antineoplastic agents (conventional cytotoxic drugs such as doxorubicin and paclitaxel, the prodrug Cholesteryl butyrate, and anti VEGF antisense oligonucleotides) have been tested in experimental animal models of cerebral gliomas. Results: SLN proved to successfully vehiculate into the brain different types of cytotoxic and gene therapeutical agents (otherwise unable to pass through the Blood-Brain Barrier) and to induce effective anti-tumoral therapeutical response. Discussion: Compared to other vehicules, SLN seem to offer more advantages (such as higher physical stability, greater protection from degradation and better release profile of incorporated drugs, good tolerability and possibility of site-specific targeting) and could be regarded as an effective carrier for chemotherapeutic drugs, gene therapeutical agents, and diagnostic tools in neuro-oncology.

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.

Complications of vagal nerve stimulation for epilepsy in children

Vagal nerve stimulation (VNS) is a surgical option to treat drug-resistant epilepsy. A few side effects have been described, mainly as anecdotal reports. We analysed our material concerning a juvenile population to identify the most common and most important complications, discussing them with the literature. Thirty-six patients were studied (18 months–18 years old). The children were assessed before the VNS implant and 3, 6, 12, 24 and 36 months after surgery. The mean follow-up was 30 months. Four patients required a second surgery: two for changing the device 3 years after implant; one for revision of an imperfect implant; one for removing a non-functioning device. In one patient a transient vocal cord paralysis was observed. Hoarseness was the main complaint (38.8%). More infrequent was mild sleep apnoea (8.3%), sternocleidomastoid muscle spasm, drooling and snoring in one patient each. Skin scars were reported with a different frequency according to the surgical technique. At variance with the literature reports, we did not observe infections. Side effects of VNS can be minimised, but not avoided completely, with a correct technical procedure, which in turn depends upon a thorough knowledge of vagus nerve anatomy.

Apathy and verbal fluency in STN-stimulated PD patients. An observational follow-up study.

ObjectiveTo evaluate apathy and its relation to verbal fluency tasks in a consecutive series of 19 patients with Parkinson’s disease (PD) submitted to deep brain stimulation of the subthalamic nucleus (DBS of STN).Methods19 consecutive PD patients submitted to bilateral DBS of STN were studied for apathy pre-operatively and 17 months after surgery. The PD patients underwent a battery of cognitive tests assessing reasoning, memory and frontal executive functions, including phonemic and categorial fluency tasks. The Beck Depression Inventory (BDI) was used for depression. Apathy was assessed by means of the Apathy Scale (AS). In order to quantify changes among individual patients, the clinical criterion of more or less than 1 SD (standard z-score) was used to register a patient as improved or worsened, respectively.ResultsAfter surgery, apathy scores did not change and mood improved (p < 0.02), while a significant worsening was found in the phonemic fluency (p < 0.001). The percentage of patients with an apathy score above the recommended cut-off value (14) was 42% both before and after DBS of STN. Individual outcomes on the apathy scale (1 SD criterion) evidenced that 53% of the patients remained stable, 16% improved, while 31% worsened. This last percentage reduced to 21% (4/19) when considering only the PD patients with an apathy score ⊕4 after surgery. No significant correlation was found between the apathy scores variation and any of the neurological variables considered, and, in particular, no correlation was found between apathy and verbal fluency.ConclusionsThe results of the present study suggest that DBS of STN does not necessarily induce apathy even if individual patients show a moderate post-operative worsening of apathetic symptoms.