Prevalence and Risk Factors of Deep Venous Thrombosis in Intensive Inpatient Neurorehabilitation Unit.

Venous thromboembolism (VTE) (deep vein thrombosis and its complication, pulmonary embolism) is a major cause of morbidity and mortality in hospitalized patients and about 7% of these cases are due to immobility secondary to a neurological impairment. Acquired brain injury (ABI) has also been recognized as one of the main risk factors for VTE. Numerous epidemiological studies have been conducted to assess the risk factors for VTE in institutionalized polytrauma patients, although there is a lack of information about neurorehabilitation wards. Since VTE is often undiagnosed, this prospective study aimed to determine the prevalence and clinical characteristics of lower-limb deep venous thrombosis (DVT) in ABI patients at neurorehabilitation admission. METHODS: ABI patients were screened for DVT on admission to the intensive rehabilitation unit (IRU) with compression ultrasonography and basal D-dimer assay and were daily clinically monitored until discharge. A total of 127 consecutive ABI patients (mean age: 60.1 ± 17.6 years; 63% male; time from event: 30.9 ± 22.1 days; rehabilitation time in IRU: 84.6 ± 58.4 days) were enrolled. RESULTS: On admission to the IRU, the DVT prevalence was about 8.6%. The mean D-dimer level in patients with DVT was significantly higher than in patients without DVT (6 ± 0.9 vs. 1.97 ± 1.61, p-value = 0.0001). ABI patients with DVT did not show any significant clinical characteristics with respect to ABI without DVT, although a prevalence of hemorrhagic strokes and patients originating from the Intensive Care Unit and Neurosurgery ward was revealed. During the rehabilitation period, patients with DVT showed a significant difference in pharmacological DVT prophylaxis (high prevalence of nadroparin with 27.3% vs. 1.7%, p-value = 0.04) and a prevalence of transfers in critical awards (36% versus 9.5% of patients without DVT, p-value = 0.05). The mortality rate was similar in the two groups. CONCLUSIONS: Our research offers a more comprehensive view of the clinical development of DVT patients and confirms the prevalence rate of DVT in ABI patients as determined upon IRU admission. According to our findings, screening these individuals regularly at the time of rehabilitation admission may help identify asymptomatic DVT quickly and initiate the proper treatment to avoid potentially fatal consequences. However, to avoid time-consuming general ultrasonography observation, a more precise selection of patients entering the rehabilitation ward is required.

Artificial neural network analysis of factors affecting functional independence recovery in patients with lumbar stenosis after neurosurgery treatment: An observational cohort study.

Background and aim: Lumbar spinal stenosis (LSS) is a leading cause of low back pain and lower limbs pain often associated with functional impairment which entails the loss or the impairment of independence in older adults. Conservative treatment is effective in a small percentage of patients, while a significant percentage undergo surgery, even if often without a complete resolution of clinical symptoms and motor deficits. The aim of the study is to identify clinical and demographic prognostic factors characterising the patients who would benefit most from surgical treatment in relation to the functional independence recovery using an innovative approach based on an artificial neural network. Methods: Adult patients with LSS and indication of neurosurgical treatment were enrolled in the study. Clinical evaluation was performed in the preoperative-phase (into the 48 h before surgery) and after two months. Clinical battery investigated the motor, functional, cognitive, behavioural, and pain status. Demographics and clinical characteristics were analysed via Artificial Neural Network (ANN) using 24 input variables, 2 hidden layers and a single final output layer to predict the outcome. ANN results were compared with those of a multiple linear regression. Results: 108 patients were included in the study and 90 of them [66.5 ± 12.8 years; 27.8 % F] were submitted to surgery treatment and completed longitudinal evaluation. Statistically significant improvement was recorded in all clinical scales comparing pre- and post-surgery. The ANN results showed a prediction ability up to 81 %. Disability, functional limitations, and pain concerning clinical assessment and stature, onset and age about demographic characteristics are the main variables impacting on surgical outcome. Conclusions: ANN can support clinical decision making, using clinical and demographic characteristics of patients with LSS identifying the characteristics of those who might benefit more from the surgical treatment in terms of global functional recovery.

Electrophysiological Screening to Assess Foot Drop Syndrome in Severe Acquired Brain Injury in Rehabilitative Settings.

BACKGROUND: Foot drop syndrome (FDS), characterized by severe weakness and atrophy of the dorsiflexion muscles of the feet, is commonly found in patients with severe acquired brain injury (ABI). If the syndrome is unilateral, the cause is often a peroneal neuropathy (PN), due to compression of the nervous trunk on the neck of the fibula at the knee level; less frequently, the cause is a previous or concomitant lumbar radiculopathy. Bilateral syndromes are caused by polyneuropathies and myopathies. Central causes, due to brain or spinal injury, mimic this syndrome but are usually accompanied by other symptoms, such as spasticity. Critical illness polyneuropathy (CIP) and myopathy (CIM), isolated or in combination (critical illness polyneuromyopathy, CIPNM), have been shown to constitute an important cause of FDS in patients with ABI. Assessing the causes of FDS in the intensive rehabilitation unit (IRU) has several limitations, which include the complexity of the electrophysiological tests, limited availability of neurophysiology consultants, and the severe disturbance in consciousness and lack of cooperation from patients. OBJECTIVES: We sought to propose a simplified electrophysiological screening that identifies FDS causes, particularly PN and CIPNM, to help clinicians to recognize the significant clinical predictors of poor outcomes in severe ABI at admission to IRU. METHODS: This prospective, single-center study included 20 severe ABI patients with FDS (11 females/9 males, mean age 55.10 + 16.26; CRS-R= 11.90 + 6.32; LCF: 3.30 + 1.30; DRS: 21.45 + 3.33), with prolonged rehabilitation treatment (≥2 months). We applied direct tibialis anterior muscle stimulation (DMS) associated with peroneal nerve motor conduction evaluation, across the fibular head (NCS), to identify CIP and/or CIM and to exclude demyelinating or compressive unilateral PN. RESULTS: At admission to IRU, simplified electrophysiological screening reported four unilateral PN, four CIP and six CIM with a CIPNM overall prevalence estimate of about 50%. After 2 months, the CIPNM group showed significantly poorer outcomes compared to other ABI patients without CIPNM, as demonstrated by the lower probability of achieving endotracheal-tube weaning (20% versus 90%) and lower CRS-R and DRS scores. Due to the subacute rehabilitation setting of our study, it was not possible to evaluate the motor results of recovery of the standing position, functional walking and balance, impaired by the presence of unilateral PN. CONCLUSIONS: The implementation of the proposed simplified electrophysiological screening may enable the early identification of unilateral PN or CIPNM in severe ABI patients, thereby contributing to better functional prognosis in rehabilitative settings.

Cognitive telerehabilitation: an expert consensus paper on current evidence and future perspective.

The progressive improvement of the living conditions and medical care of the population in industrialized countries has led to improvement in healthcare interventions, including rehabilitation. From this perspective, Telerehabilitation (TR) plays an important role. TR consists of the application of telemedicine to rehabilitation to offer remote rehabilitation services to the population unable to reach healthcare. TR integrates therapy-recovery-assistance, with continuity of treatments, aimed at neurological and psychological recovery, involving the patient in a family environment, with an active role also of the caregivers. This leads to reduced healthcare costs and improves the continuity of specialist care, as well as showing efficacy for the treatment of cognitive disorders, and leading to advantages for patients and their families, such as avoiding travel, reducing associated costs, improving the frequency, continuity, and comfort of performing the rehabilitation in its own spaces, times and arrangements. The aim of this consensus paper is to investigate the current evidence on the use and effectiveness of TR in the cognitive field, trying to also suggest some recommendations and future perspectives. To the best of our knowledge, this is the first consensus paper among multiple expert researchers that comprehensively examines TR in different neurological diseases. Our results supported the efficacy and feasibility of TR with good adherence and no adverse events among patients. Our consensus summarizes the current evidence for the application of cognitive TR in neurological populations, highlighting the potential of this tool, but also the limitations that need to be explored further.

Exploitation of Autophagy Inducers in the Management of Dementia: A Systematic Review.

The social burden of dementia is remarkable since it affects some 57.4 million people all over the world. Impairment of autophagy in age-related diseases, such as dementia, deserves deep investigation for the detection of novel disease-modifying approaches. Several drugs belonging to different classes were suggested to be effective in managing Alzheimer's disease (AD) by means of autophagy induction. Useful autophagy inducers in AD should be endowed with a direct, measurable effect on autophagy, have a safe tolerability profile, and have the capability to cross the blood-brain barrier, at least with poor penetration. According to the PRISMA 2020 recommendations, we propose here a systematic review to appraise the measurable effectiveness of autophagy inducers in the improvement of cognitive decline and neuropsychiatric symptoms in clinical trials and retrospective studies. The systematic search retrieved 3067 records, 10 of which met the eligibility criteria. The outcomes most influenced by the treatment were cognition and executive functioning, pointing at a role for metformin, resveratrol, masitinib and TPI-287, with an overall tolerable safety profile. Differences in sample power, intervention, patients enrolled, assessment, and measure of outcomes prevents generalization of results. Moreover, the domain of behavioral symptoms was found to be less investigated, thus prompting new prospective studies with homogeneous design. PROSPERO registration: CRD42023393456.

Central autonomic network and early prognosis in patients with disorders of consciousness.

The central autonomic network (CAN) plays a crucial role in modulating the autonomic nervous system. Heart rate variability (HRV) is a valuable marker for assessing CAN function in disorders of consciousness (DOC) patients. We used HRV analysis for early prognosis in 58 DOC patients enrolled within ten days of hospitalization. They underwent a five-minute electrocardiogram during baseline and acoustic/visual stimulation. The coma recovery scale-revised (CRS-R) was used to define the patient's consciousness level and categorize the good/bad outcome at three months. The high-frequency Power Spectrum Density and the standard deviation of normal-to-normal peaks in baseline, the sample entropy during the stimulation, and the time from injury features were used in the support vector machine analysis (SVM) for outcome prediction. The SVM predicted the patients' outcome with an accuracy of 96% in the training test and 100% in the validation test, underscoring its potential to provide crucial clinical information about prognosis.

Inducing Cough Reflex by Capsaicin Spray Stimulation in Patients with Acquired Brain Injury: A Preliminary Test and Proof of Concept.

Individuals with acquired brain injuries (ABIs) may experience various complications related to poor coughing or impaired cough reflex (including risk of aspiration pneumonia or respiratory infections). For this reason, cough assessment is an important component in the clinical evaluation since patients with ABI are not able to cough voluntarily due to severe motor deficits. When voluntarily coughing is not possible, it is essential for clinical practices to find a quick and minimally invasive way to induce a cough reflex. In the present study, we evaluated the cough reflex in ABI patients using a new method based on a capsaicin spray stimulation test. In total, 150 healthy controls demographically matched with 50 ABI patients were included in this study. Clinical observations demonstrated robust cough response in both healthy controls and ABI patients, as well as the safety and tolerability of capsaicin spray stimulation. ABI patients with dysphagia were characterized by slower and delayed cough responses. Further studies are needed to validate this feasible, less-invasive, and simple-to-comprehend technique in inducing cough reflex. According to this preliminary evidence, we believe that this test might be translated into a simple and effective treatment to improve reflexive cough modulation in ABI patients.

Enhancing the Quality of Life of Patients with Multiple Sclerosis: Promising Results on the Role of Cognitive Tele-Rehabilitation Plus Virtual Reality.

(1) Background: Patients with multiple sclerosis often face obstacles accessing traditional rehabilitation programs, primarily due to mobility limitations. Tele-rehabilitation (TR) is seen as a promising solution to overcome these barriers, though its precise influence on patients' quality of life (QoL) has not been thoroughly investigated. Thus, the aim of the present study was to assess the feasibility of a cognitive TR in a sample of Italian patients with MS. (2) Methods: Thirty-six patients diagnosed with MS, attending the Robotic and Behavioral Neurorehabilitation Unit of the IRCCS "Bonino-Pulejo" Neurolesi Center in Messina, Italy, between October 2019 and March 2020 were enrolled in the study. All patients were randomly assigned, using block randomization with a block size of 2 × 2, to two groups: the control group (CG), composed of 16 patients who received traditional cognitive training, and the experimental group (EG), composed of 20 patients who underwent TR training with a VRRS (virtual reality rehabilitation system). Each patient underwent an assessment before (T0) and immediately after (T1) the rehabilitation treatment, using the Quality of Life-54 Multiple Sclerosis (MSQoL-54). (3) Results: Only in the EG, we observed a statistically significant improvement in the QoL related to mental well-being following the paired T-test (MSQoL p-value < 0.001). Notably, no significant differences were found in the CG (MSQoL p-value of 0.67). (4) Conclusions: Our data suggest that TR training combined with VR has the potential to improve the well-being of individuals with MS.

MR-Guided Focused Ultrasound for Refractory Epilepsy: Where Are We Now?

Epilepsy is one of the most common neurological diseases in both adults and children. Despite improvements in medical care, 20 to 30% of patients are still resistant to the best medical treatment. The quality of life, neurologic morbidity, and even mortality of patients are significantly impacted by medically intractable epilepsy. Nowadays, conservative therapeutic approaches consist of increasing medication dosage, changing to a different anti-seizure drug as monotherapy, and combining different antiseizure drugs using an add-on strategy. However, such measures may not be sufficient to efficiently control seizure recurrence. Resective surgery, ablative procedures and non-resective neuromodulatory (deep-brain stimulation, vagus nerve stimulation) treatments are the available treatments for these kinds of patients. However, invasive procedures may involve lengthy inpatient stays for the patients, risks of long-term neurological impairment, general anesthesia, and other possible surgery-related complications (i.e., hemorrhage or infection). In the last few years, MR-guided focused ultrasound (MRgFUS) has been proposed as an emerging treatment for neurological diseases because of technological advancements and the goal of minimally invasive neurosurgery. By outlining the current knowledge obtained from both preclinical and clinical studies and discussing the technical opportunities of this therapy for particular epileptic phenotypes, in this perspective review, we explore the various mechanisms and potential applications (thermoablation, blood-brain barrier opening for drug delivery, neuromodulation) of high- and low-intensity ultrasound, highlighting possible novel strategies to treat drug-resistant epileptic patients who are not eligible or do not accept currently established surgical approaches. Taken together, the available studies support a possible role for lesional treatment over the anterior thalamus with high-intensity ultrasound and neuromodulation of the hippocampus via low-intensity ultrasound in refractory epilepsy. However, more studies, likely conceiving epilepsy as a network disorder and bridging together different scales and modalities, are required to make ultrasound delivery strategies meaningful, effective, and safe.

Effect of genotype on individual response to the pharmacological treatment of glaucoma: a systematic review and meta-analysis.

The social impact of glaucoma is worth of note: primary open-angle glaucoma (POAG) is one of the leading causes of irreversible blindness worldwide, affecting some 68.56 million people with overall prevalence of 2.4%. Since one of the main risk factors for the development of POAG is the increase of intraocular pressure (IOP) causing retinal ganglion cells death, the medical treatment of POAG consists in the use of drugs endowed with neuroprotective effect and able to reduce IOP. These drugs include beta-blockers, prostaglandin analogues, carbonic anhydrase inhibitors, alpha or cholinergic agonists and rho kinase inhibitors. However, not all the patients respond to the same extent to the therapy in terms of efficacy and safety. Genetics and genome wide association studies have highlighted the occurrence of mutations and polymorphisms influencing the predisposition to develop POAG and its phenotype, as well as affecting the response to pharmacological treatment. The present systematic review and meta-analysis aims at identifying genetic variants and at verifying whether these can influence the responsiveness of patients to therapy for efficacy and safety. It follows the most updated Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 recommendations. The literature search was conducted consulting the most relevant scientific databases, i.e. PubMed/MEDLINE, Scopus, Web of Science and Public Health Genomics and Precision Health Knowledge Base up to June 14th, 2023. The search retrieved 1026 total records, among which eight met the eligibility criteria for inclusion in the analysis. The results demonstrated that the most investigated pharmacogenetic associations concern latanoprost and timolol, and that efficacy was studied more in depth than safety. Moreover, the heterogeneity of design and paucity of studies prompt further investigation in randomized clinical trials. In fact, adequately powered and designed pharmacogenetic association studies are needed to provide body of evidence with good certainty for a more appropriate use of medical therapy in POAG.PROSPERO registration: CRD42023434867.

Computer-assisted cognitive rehabilitation in neurological patients: state-of-art and future perspectives.

Background and aim: Advances in computing technology enabled researchers and clinicians to exploit technological devices for cognitive training and rehabilitation interventions. This expert review aims to describe the available software and device used for cognitive training or rehabilitation interventions of patients with neurological disorders. Methods: A scoping review was carried out to analyze commercial devices/software for computerized cognitive training (CCT) in terms of feasibility and efficacy in both clinical and home settings. Several cognitive domains responding to the different patients' needs are covered. Results: This review showed that cognitive training for patients with neurological diseases is largely covered by several devices that are widely used and validated in the hospital setting but with few translations to remote/home applications. It has been demonstrated that technology and software-based devices are potential and valuable tools to administer remotely cognitive rehabilitation with accessible costs. Conclusion: According to our results, CCT entails the possibility to continue cognitive training also in different settings, such as home, which is a significant breakthrough for the improvement of community care. Other possible areas of use should be the increase in the amount of cognitive therapy in the free time during the hospital stay.

Assessing Consciousness through Neurofeedback and Neuromodulation: Possibilities and Challenges.

Neurofeedback is a non-invasive therapeutic approach that has gained traction in recent years, showing promising results for various neurological and psychiatric conditions. It involves real-time monitoring of brain activity, allowing individuals to gain control over their own brainwaves and improve cognitive performance or alleviate symptoms. The use of electroencephalography (EEG), such as brain-computer interface (BCI), transcranial direct current stimulation (tDCS), and transcranial magnetic stimulation (TMS), has been instrumental in developing neurofeedback techniques. However, the application of these tools in patients with disorders of consciousness (DoC) presents unique challenges. In this narrative review, we explore the use of neurofeedback in treating patients with DoC. More specifically, we discuss the advantages and challenges of using tools such as EEG neurofeedback, tDCS, TMS, and BCI for these conditions. Ultimately, we hope to provide the neuroscientific community with a comprehensive overview of neurofeedback and emphasize its potential therapeutic applications in severe cases of impaired consciousness levels.

I Feel! Therefore, I Am from Pain to Consciousness in DOC Patients.

Pain assessment and management in patients with disorders of consciousness (DOC) is a challenging and important aspect of care, with implications for detecting consciousness and promoting recovery. This narrative review explores the role of pain in consciousness, the challenges of pain assessment, pharmacological treatment in DOC, and the implications of pain assessment when detecting changes in consciousness. The review discusses the Nociception Coma Scale and its revised version, which are behavioral scales used to assess pain in DOC patients, and the challenges and controversies surrounding the appropriate pharmacological treatment of pain in these patients. Moreover, we highlight recent evidence suggesting that an accurate pain assessment may predict changes in the level of consciousness in unresponsive wakefulness syndrome/vegetative state patients, underscoring the importance of ongoing pain management in these patients.

Benefits of Telerehabilitation for Patients With Severe Acquired Brain Injury: Promising Results From a Multicenter Randomized Controlled Trial Using Nonimmersive Virtual Reality.

BACKGROUND: In neurorehabilitation, the use of innovative technologies offers many opportunities to monitor and improve the health status of patients with severe acquired brain injury (SABI). Telerehabilitation allows for continuity of service through the entire rehabilitation cycle, including assessment, intervention, consultation, and education, affording early reintegration and positively enhancing the quality of life (QoL). OBJECTIVE: The main purpose of this multicenter randomized controlled trial was to test the effectiveness of advanced training provided using a nonimmersive virtual reality rehabilitation system (ie, the VRRS HomeKit device) in improving functional outcomes in patients with SABI. METHODS: In total, 40 patients with SABI and their 40 caregivers visiting 2 Italian rehabilitation centers were enrolled in the study protocol and randomized into 2 groups. Of the 40 patients, 20 (50%) underwent the experimental training using the VRRS HomeKit (teleneuro-VRRS group), whereas the other 20 (50%) were administered usual territorial rehabilitative treatments (UTRTs; control group). To investigate motor and neuropsychological functioning, patients with SABI were evaluated before (T0) and at the end of (T1) each training session by a multispecialist team through a complete clinical and psychometric battery: the Barthel Index (BI), the Tinetti Scale (TS), the Modified Ashworth Scale (MAS), the Montreal Cognitive Assessment (MoCa), the Frontal Assessment Battery (FAB), the Beck Depression Inventory II (BDI-II), the Short Form Health Survey 36 (SF-36), and the Psychological General Well-Being Index (PGWBI). In addition, the Caregiver Burden Inventory (CBI) was administered to each caregiver to investigate the emotional burden status. RESULTS: The teleneuro-VRRS group achieved a statistically significant improvement in both general and motor outcomes, as well as psychological well-being and QoL, compared to the control group. In particular, the BI (P<.001), FAB (P<.001), and BDI-II (P<.001) were the outcome scales with the best improvement. The burden of caregivers also significantly improved in the teleneuro-VRRS group (CBI; P<.004). Between-group analysis showed statistical differences in the anxiety (effect size [ES]=0.85, P<.02) and self-control (ES=0.40, P<.03) subtests of the PGWBI and in the social role functioning (ES=0.85, P<.02) subtest of the SF-36, confirmed by quite medium and large ESs. CONCLUSIONS: Our results suggest that the VRRS is a suitable alternative tool or complementary tool or both to improve motor (level of functional independence) and cognitive (frontal/executive abilities) outcomes, reducing behavioral alterations (anxiety and depression symptoms) in patients with SABI, with a beneficial impact also on the caregivers' burden distress management, mitigating distress and promoting positive aspects of caring. TRIAL REGISTRATION: ClinicalTrials.gov NCT03709875; https://classic.clinicaltrials.gov/ct2/show/NCT03709875.

Talking about Sexuality in Stroke Individuals: The New Era of Sexual Rehabilitation.

One of the largest causes of mortality and disability worldwide is stroke. In the last twenty years significant objectives have been achieved in the early and chronic treatment of motor and cognitive dysfunctions, increasing the quality of life in patients and their caregivers. However, there is an unresolved clinical issue that remains: sexual dysfunctions. Multiple etiologies, including organic (such as lesion localization, premorbid medical problems, and drugs) and psychosocial (such as fear of recurrences, loss of self-esteem, role shifts, anxiety, and depression), are associated with sexual deficits. In this perspective review, we reported the last piece of evidence about this crucial topic which drastically affects the quality of life of these patients. Indeed, although patients may often not disclose their sexual concerns, literature demonstrates that they seek help concerning this issue. On the other side, clinicians working in the rehabilitation field are not always comfortable or prepared to deal with sexuality and sexual function in neurological patients. A new phase of the training course should be launched including different physicians, nurses, rehabilitation specialists, and social workers, to learn how to deal with topics related to sexuality. As a result, professional sexual counselors should now become a structured part of stroke settings and rehabilitation with new effective tools (i.e., PLISSIT model; TDF program) for improving quality of life.

Safety of Onabotulinumtoxin A in Chronic Migraine: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Some 14% of global prevalence, based on high-income country populations, suffers from migraine. Chronic migraine is very disabling, being characterized by at least 15 headache days per month of which at least 8 days present the features of migraine. Onabotulinumtoxin A, targeting the machinery for exocytosis of neurotransmitters and neuropeptides, has been approved for use in chronic migraine since 2010. This systematic review and meta-analysis appraises the safety of onabotulinumtoxin A treatment for chronic migraine and the occurrence of treatment-related adverse events (TRAEs) in randomized, clinical studies in comparison with placebo or other comparators and preventative treatments according to the most updated Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 recommendations. The search retrieved 888 total records. Nine studies are included and seven were eligible for meta-analysis. The present study demonstrates that toxin produces more TRAEs than placebo, but less than oral topiramate, supporting the safety of onabotulinumtoxin A, and highlights the heterogeneity of the studies present in the literature (I2 = 96%; p < 0.00001). This points to the need for further, adequately powered, randomized clinical trials assessing the safety of onabotulinumtoxin A in combination with the newest treatment options.

Modeling outcome trajectories in patients with acquired brain injury using a non-linear dynamic evolution approach.

This study describes a dynamic non-linear mathematical approach for modeling the course of disease in acquired brain injury (ABI) patients. Data from a multicentric study were used to evaluate the reliability of the Michaelis-Menten (MM) model applied to well-known clinical variables that assess the outcome of ABI patients. The sample consisted of 156 ABI patients admitted to eight neurorehabilitation subacute units and evaluated at baseline (T0), 4 months after the event (T1) and at discharge (T2). The MM model was used to characterize the trend of the first Principal Component Analysis (PCA) dimension (represented by the variables: feeding modality, RLAS, ERBI-A, Tracheostomy, CRS-r and ERBI-B) in order to predict the most plausible outcome, in terms of positive or negative Glasgow outcome score (GOS) at discharge. Exploring the evolution of the PCA dimension 1 over time, after day 86 the MM model better differentiated between the time course for individuals with a positive and negative GOS (accuracy: 85%; sensitivity: 90.6%; specificity: 62.5%). The non-linear dynamic mathematical model can be used to provide more comprehensive trajectories of the clinical evolution of ABI patients during the rehabilitation period. Our model can be used to address patients for interventions designed for a specific outcome trajectory.

Efficacy of Essential Oils in Relieving Cancer Pain: A Systematic Review and Meta-Analysis.

Over 80% of patients affected by cancer develops cancer-related pain, one of the most feared consequences because of its intractable nature, particularly in the terminal stage of the disease. Recent evidence-based recommendations on integrative medicine for the management of cancer pain underline the role of natural products. The present systematic review and meta-analysis aims at appraising for the first time the efficacy of aromatherapy in cancer pain in clinical studies with different design according to the most updated Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 recommendations. The search retrieves 1002 total records. Twelve studies are included and six are eligible for meta-analysis. The present study demonstrates significant efficacy of the use of essential oils in the reduction of the intensity of pain associated with cancer (p < 0.00001), highlighting the need for earlier, more homogeneous, and appropriately designed clinical trials. Good certainty body of evidence is needed for effective and safe management of cancer-related pain using essential oils by establishment of a step-by-step preclinical-to-clinical pathway to provide a rational basis for clinical use in integrative oncology. PROSPERO registration: CRD42023393182.

Behavioral scales variability in patients with prolonged disorders of consciousness.

BACKGROUND: The principal conditions differentiating disorders of consciousness (DOC) patients are the unresponsive wakefulness syndrome/vegetative state (UWS/VS) and the minimally conscious state (MCS). Many individuals who suffer from sudden-onset severe brain injury move through stages of UWS/VS and MCS before regaining full awareness. In some patients, the DOC condition is protracted for years (PDOC). In this study, we observed PDOC patients for 6 months to assess possible changes in their level of consciousness. METHODS: We enrolled 40 PDOC patients, 23 UWS/VS and 17 MCS hosted in a dedicated unit for long-term brain injury care. The time from injury was 472 ± 533 days for UWS/VS and 1090 ± 1079 days for MCS. The Wessex Head Injury Matrix (WHIM), Coma Recovery Scale-R (CRS-R), and Nociception Coma Scale were administered monthly for 6 months. RESULTS: During the period of assessment, the percentage of UWS/VS shifted from 58 to 45%, while for the MCS, from 42 to 55%. A positive correlation was found for the UWS/VS patients between the months of observation with the CRS-R total score and WHIM total numbers of behaviors (TNB). In the UWS/VS group, the CRS-R auditive and visual subscales correlated positively with the observation time. During the whole period of observation, 8 patients had constant CRS-R total scores while the WHIM TNB changed in 7 of them. CONCLUSION: Our findings demonstrated that the monthly assessment of PDOC by means of the CRS-R and WHIM was able to detect also subtle changes in consciousness level.

Sleep in Disorders of Consciousness: A Brief Overview on a Still under Investigated Issue.

Consciousness is a multifaceted concept, involving both wakefulness, i.e., a condition of being alert that is regulated by the brainstem, and awareness, a subjective experience of any thoughts or perception or emotion. Recently, the European Academy of Neurology has published international guidelines for a better diagnosis of coma and other disorders of consciousness (DOC) through the investigation of sleep patterns, such as slow-wave and REM, and the study of the EEG using machine learning methods and artificial intelligence. The management of sleep disorders in DOC patients is an increasingly hot topic and deserves careful diagnosis, to allow for the most accurate prognosis and the best medical treatment possible. The aim of this review was to investigate the anatomo-physiological basis of the sleep/wake cycle, as well as the main sleep patterns and sleep disorders in patients with DOC. We found that the sleep characteristics in DOC patients are still controversial. DOC patients often present a theta/delta pattern, while epileptiform activity, as well as other sleep elements, have been reported as correlating with outcomes in patients with coma and DOC. The absence of spindles, as well as REM and K-complexes of NREM sleep, have been used as poor predictors for early awakening in DOC patients, especially in UWS patients. Therefore, sleep could be considered a marker of DOC recovery, and effective treatments for sleep disorders may either indirectly or directly favor recovery of consciousness.