Behavioral and Psychiatric Symptoms in Patients with Severe Traumatic Brain Injury: A Comprehensive Overview.

Traumatic brain injury (TBI) is defined as an altered brain structure or function produced by an external force. Adults surviving moderate and severe TBI often experience long-lasting neuropsychological and neuropsychiatric disorders (NPS). NPS can occur as primary psychiatric complications or could be an exacerbation of pre-existing compensated conditions. It has been shown that changes in behavior following moderate to severe TBI have a prevalence rate of 25-88%, depending on the methodology used by the different studies. Most of current literature has found that cognitive behavioral and emotional deficit following TBI occurs within the first six months whereas after 1-2 years the condition becomes stable. Identifying the risk factors for poor outcome is the first step to reduce the sequelae. Patients with TBI have an adjusted relative risk of developing any NPS several-fold higher than in the general population after six months of moderate-severe TBI. All NPS features of an individual's life, including social, working, and familiar relationships, may be affected by the injury, with negative consequences on quality of life. This overview aims to investigate the most frequent psychiatric, behavioral, and emotional symptoms in patients suffering from TBI as to improve the clinical practice and tailor a more specific rehabilitation training.

Gender and Neurosteroids: Implications for Brain Function, Neuroplasticity and Rehabilitation.

Neurosteroids are synthesized de novo in the nervous system; they mainly moderate neuronal excitability, and reach target cells via the extracellular pathway. The synthesis of neurosteroids occurs in peripheral tissues such as gonads tissues, liver, and skin; then, because of their high lipophilia, they cross the blood-brain barrier and are stored in the brain structure. Neurosteroidogenesis occurs in brain regions such as the cortex, hippocampus, and amygdala by enzymes necessary for the in situ synthesis of progesterone from cholesterol. Neurosteroids could be considered the main players in both sexual steroid-induced hippocampal synaptic plasticity and normal transmission in the hippocampus. Moreover, they show a double function of increasing spine density and enhancing long term potentiation, and have been related to the memory-enhancing effects of sexual steroids. Estrogen and progesterone affect neuronal plasticity differently in males and females, especially regarding changes in the structure and function of neurons in different regions of the brain. Estradiol administration in postmenopausal women allowed for improving cognitive performance, and the combination with aerobic motor exercise seems to enhance this effect. The paired association between rehabilitation and neurosteroids treatment could provide a boosting effect in order to promote neuroplasticity and therefore functional recovery in neurological patients. The aim of this review is to investigate the mechanisms of action of neurosteroids as well as their sex-dependent differences in brain function and their role in neuroplasticity and rehabilitation.

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.

A multidisciplinary advanced approach in central pontine myelinolysis recovery: considerations about a case report.

BACKGROUND AND PURPOSE: Central pontine myelinolysis (CPM) is a solitary, symmetric, demyelination in the central pons. This case study aimed to report the effects of an intensive robotic gait training with Lokomat-Pro on mobility and quality of life in a case of CPM. CASE DESCRIPTION AND INTERVENTION: A 33-year-old female patient with tetraparesis and gait disturbance due to CPM was hospitalized to undergo intensive rehabilitation training for about 2 months. Daily session of Lokomat-Pro and psychotherapy by telemedicine were performed, besides nursing care and occupational and physical therapy. Motor evaluation and quality of life were assessed by using standardized scales. OUTCOMES: The multidisciplinary therapy led to significant improvements both in functional motor outcomes (as per 10-Meter Walk Test, Berg Balance and Tinetti scale) and quality of life. DISCUSSION: Innovation technology, including robotics and telemedicine, may be a valuable tool to improve functional outcomes in patients with severe motor impairment due to chronic CPM.IMPLICATIONS FOR REHABILITATIONA multidisciplinary approach involving robotics plus virtual reality is mandatory to reduce medical and bedridden complications in patients affected by CPM.

Chronic Migraine: A Narrative Review on the Use of Botulinum Toxin with Clinical Indications and Future Directions.

Chronic migraine belongs to the "chronic long-duration headaches", and it is associated to high burden and significant economic impact. Treatment for both episodic (EM) and chronic migraine (CM) is based on the management of acute attacks and their prevention. For moderate/severe attacks, pharmacological therapies are triptans, dihydroergotamine nasal sprays or injections or neuroleptics, non-steroidal anti-inflammatory drugs, and corticosteroids. Chronic migraine belongs to the "chronic long-duration headaches", and it is associated to high burden and significant economic impact. Treatment for both episodic (EM) and chronic migraine (CM) is based on the management of acute attacks and their prevention. For moderate/severe attacks, pharmacological therapies are triptans, dihydroergotamine nasal sprays or injections or neuroleptics, non-steroidal anti-inflammatory drugs, and corticosteroids. The pathophysiology of CM is characterized by an abnormal activation of the trigemino-vascular system in the meninges causing a neurogenic inflammation, which explains the use of anti-inflammatory during attacks. It seems that the objective of the preventive therapy with the botulin toxin OnaBoNT-A consists in interrupting the release of CGRP and other neuropeptides as well as the activation of C-fiber nociceptor and of the nearby A-delta fibers. The protocol for migraine treatment with OnaBoNT-A injections consists of 31-39 pericranial injection sites involving seven muscle groups bilaterally in specific areas of the head and neck, with a total dose of between 155 and 195 units, every three months. The severe adverse events reported with high doses of botulin toxin for spasticity, have not been reported for CM treated with OnabotA at the labeled dose. The established improvement with onabotulinumtoxinA treatment in CM patients had a positive impact not only in reduction monthly headache days but also in improving quality of life, with reduction in both healthcare resource utilisation (HRU) and work impairment. Aim of this review was to give an overview on the use of BoNT-A in patients with CM, giving practical advices on the clinical indications.

The Use of Palmitoylethanolamide in the Treatment of Long COVID: A Real-Life Retrospective Cohort Study.

COVID-19 can cause symptoms that last weeks or months after the infection has gone, with a significant impairment of quality of life. Palmitoylethanolamide (PEA) is a naturally occurring lipid mediator that has an entourage effect on the endocannabinoid system mitigating the cytokine storm. The aim of this retrospective study is to evaluate the potential efficacy of PEA in the treatment of long COVID. Patients attending the Neurological Out Clinic of the IRCCS Centro Neurolesi Bonino-Pulejo (Messina, Italy) from August 2020 to September 2021 were screened for potential inclusion in the study. We included only long COVID patients who were treated with PEA 600 mg two times daily for about 3 months. All patients performed the post-COVID-19 Functional Status (PCFS) scale. Thirty-three patients (10 males, 43.5%, mean age 47.8 ± 12.4) were enrolled in the study. Patients were divided into two groups based on hospitalization or home care observation. A substantial difference in the PCFS score between the two groups at baseline and after treatment with PEA were found. We found that smoking was a risk factor with an odds ratio of 8.13 CI 95% [0.233, 1.167]. Our findings encourage the use of PEA as a potentially effective therapy in patients with long COVID.

Improving Upper Extremity Bradykinesia in Parkinson's Disease: A Randomized Clinical Trial on the Use of Gravity-Supporting Exoskeletons.

Hand movements are particularly impaired in patients with Parkinson's Disease (PD), contributing to functional disability and difficulties in activities of daily living. Growing evidence has shown that robot-assisted therapy may be considered an effective and reliable method for the delivery of the highly repetitive training that is needed to trigger neuroplasticity, as intensive, repetitive and task-oriented training could be an ideal strategy to facilitate the relearning of motor function and to minimize motor deficit. The purpose of this study is to evaluate the improvement of hand function with semi-autonomous exercises using an upper extremity exoskeleton in patients with PD. A multicenter, parallel-group, randomized clinical trial was then carried out at the IRCCS Centro Neurolesi Bonino-Pulejo (Messina, Italy). Thirty subjects with a diagnosis of PD and a Hoehn-Yahr score between 2 and 3 were enrolled in the study. Patients were 1:1 randomized into either the experimental group (ERT), receiving 45 min training daily, 6 days weekly, for 8 weeks with Armeo®Spring (Volketswil, Switzerland) (a gravity-supporting device), or the control group (CPT), which was subjected to the same amount of conventional physical therapy. Motor abilities were assessed before and after the end of the training. The main outcomes measures were the Nine-hole peg test and the motor section of the UPDRS. All patients belonging to ERT and 9 out of 15 patients belonging to the CPT completed the trial. ERT showed a greater improvement in the primary outcome measure (nine-hole peg test) than CPT. Moreover, a statistically significant improvement was found in ERT concerning upper limb mobility, and disease burden as compared to CPT. Using an upper extremity exoskeleton (i.e., the Armeo®Spring) for semi-autonomous training in an inpatient setting is a new perspective to train patients with PD to improve their dexterity, executive function and, potentially, quality of life.

Could Palmitoylethanolamide Be an Effective Treatment for Long-COVID-19? Hypothesis and Insights in Potential Mechanisms of Action and Clinical Applications.

COVID-19 is highly transmissive and contagious disease with a wide spectrum of clinicopathological issues, including respiratory, vasculo-coagulative, and immune disorders. In some cases of COVID-19, patients can be characterized by clinical sequelae with mild-to-moderate symptoms that persist long after the resolution of the acute infection, known as long-COVID, potentially affecting their quality of life. The main symptoms of long-COVID include persistent dyspnea, fatigue and weakness (that are typically out of proportion, to the degree of ongoing lung damage and gas exchange impairment), persistence of anosmia and dysgeusia, neuropsychiatric symptoms, and cognitive dysfunctions (such as brain fog or memory lapses). The appropriate management and prevention of potential long-COVID sequelae is still lacking. It is also believed that long-term symptoms of COVID-19 are related to an immunity over-response, namely a cytokine storm, involving the release of pro-inflammatory interleukins, monocyte chemoattractant proteins, and tissue necrosis factors. Palmitoylethanolamide (PEA) shows affinity for vanilloid receptor 1 and for cannabinoid-like G protein-coupled receptors, enhancing anandamide activity by means of an entourage effect. Due to its anti-inflammatory properties, PEA has been recently used as an early add-on therapy for respiratory problems in patients with COVID-19. It is believed that PEA mitigates the cytokine storm modulating cell-mediated immunity, as well as counteracts pain and oxidative stress. In this article, we theorize that PEA could be a potentially effective nutraceutical to treat long-COVID, with regard to fatigue and myalgia, where a mythocondrial dysfunction is hypothesizable.

Neurogenic Dysphagia and Nutrition in Disorder of Consciousness: An Overview with Practical Advices on an "Old" but Still Actual Clinical Problem.

Neurogenic dysphagia is a difficulty in swallowing food caused by disease or impairment of the nervous system, including stroke and traumatic brain injury. The most clinically apparent complication of neurogenic dysphagia is pulmonary aspiration, which may manifest itself acutely as choking or coughing, respiratory distress, wheezing, gasping or gurgling, and tachycardia. However, chronic symptoms, including weight loss, production of excessive oral secretions and aspiration pneumonia, may be also present, especially in patients with a disorder of consciousness (DOC). Usually, patients with dysphagia after the acute phase need to be treated with enteral nutrition using a feeding tube. This avoids patient malnutrition and supports the rehabilitation program. This narrative review aims to investigate dysphagia and its complications and management in patients with DOC. Clinical indications and practical advice on how to assess and treat this complex problem are also provided.

Neurological complications of COVID-19: from pathophysiology to rehabilitation. An overview.

OBJECTIVE: To evaluate how the SARS-COV2 is able to affect the nervous system, the main neurological manifestation, and the treatment used, including neurorehabilitation. METHODS: Studies performed during the current year that fulfilled inclusion criteria were selected from PubMed, Scopus, Cochrane, and Web of Sciences databases. The search combined the terms "Covid 19," "rehabilitation/treatment," and "neurological complications." RESULTS: The exact route by which SARS-CoV-2 can penetrate the CNS is still unknown, although a possible retrograde transynaptic pathway from peripheral nerve endings, and/or through the olfactory bulb, have been suggested. An early management of COVID-19 by a multiprofessional team is fundamental to avoid long term sequaele. Rehabilitation is recommended to improve respiratory and cardiac function, as well as to avoid long term neurological complications. CONCLUSIONS: As no specific conclusions in term of prognosis and treatment could be done, research and consensus paper are needed to provide NeuroCovid patients with the best treatment options, including neurorehabilitation.

The relationship between body image and emotional and cognitive impairment after brain damage: A preliminary study.

INTRODUCTION: The image of one's own body derives from experimentation of one's own body pattern. The emotional experience can lead to a real or distorted self-representation. After brain damage, a disorder of body image is frequent. The purpose of this study was to investigate the role of body image following acquired brain injury (ABI). METHODS: Forty-six hospitalized patients were enrolled and subdivided into two groups depending on the etiology of the damage: traumatic or vascular. For each group, we considered their cognitive level and mood. Patients underwent a broad battery of tests to investigate different domains: Montreal Cognitive Assessment (MoCA); Beck's Depression Inventory (BDI-II); Hamilton Rating Scale for Anxiety (HAM-A); Clinical Insight Rating Scale (CIRS); Body Image Scale (BIS); Human Figure Drawing (HFD). The latter was used to assess the implicit body image of each patient. RESULTS: Both groups showed a significant relationship between BDI-II and BIS. A positive correlation was found between BIS and HAM-A, but only in the traumatic group. We showed a positive correlation between MoCA and HFD. In addition, we observed some subitems of MoCA as predictive variables in HFD, which differ in the two groups. In a traumatic group, the visuospatial domain is predictive in HFD, as well as age of patients' and education. In the vascular groups, orientation, naming, abstraction, and language domains are instead predictive. CONCLUSIONS: The results confirm the crucial role of the cognitive level and mood on self-perception.

Nursing, Caregiving and Psychological support in Chronic Disorders of Consciousness: a scoping review.

BACKGROUND AND AIMS: The major disorders of consciousness include Coma, Vegetative State, and Minimally Conscious State. The care and the management of patients with Disorders of Consciousness (DOC) have raised several important ethical, social and medical issues. Aim of this review is to evaluate the role of nursing and psychological support in DOC management, in order to improve the quality of life of both patients and their caregivers. METHODS: Studies dealing with DOC, nursing and caregiving pubblished in the last 20 years (from January 2000 to June 2020) were identified by searching on PubMed, Web of Science and Cochrane databases. RESULTS: This review highlights the important role of DOC carevigers in the complex management of these frail patients, as well as the need for a specific support and counselling of caregivers. This psychological support may be given by nurses, as they are the healthcare professionals more involved in DOC care and cure. DISCUSSION: Over the last years, specific recommendations for the assessment and rehabilitation of patients with DOC have been promulgated by neurorehabilitation organizations to provide some guidelines for the care and cure of such frail patients. Indeed, DOC patients need a multidisciplinary approach in which both caregivers and nurses have a pivotal role. CONCLUSIONS: As the family is a critical and fundamental aspect in the management of DOC patients, it should be considered an integral part of care in the future guidelines.

Can powered exoskeletons improve gait and balance in multiple sclerosis? A retrospective study.

Multiple sclerosis (MS) is a progressive neurologic disorder that can profoundly influence mobility, independence and quality of life. Gait dysfunction in MS is common, resulting in an increased risk of losing walking ability. Robotic exoskeletons have been developed to offer a new form of locomotor training. The aim of our study was to investigate the effectiveness of the powered exoskeleton (Ekso) in improving gait and balance in patients affected by MS. Twenty patients with MS (mean ± SD: age = 43.7 ± 10.3 years; 66.7% male) were enrolled in this retrospective study. They were divided into two groups, matched for demographic data (age and sex) and medical characteristics (disease duration and Expanded Disability Status Scale), but differing for the type of rehabilitation training performed. Group 1 [experimental group (EG)] received gait training with the Ekso device, whereas group 2 (control group) performed traditional gait training. Although both trainings led to a significant improvement in the ability to walk and balance, only in the EG a significant improvement in walking speed (10 Meter Walk test; P = 0.002), in person's mobility (Timed Up and Go test; P = 0.002), and in the perception of mental well-being (MSQoL-M; P = 0.004), with a good usability and acceptance of the device, was found. Powered exoskeletons could be considered a valuable tool to improve functional outcomes and get the therapeutic goal in patients with MS.

A Case Report on Robot-Aided Gait Training in Primary Lateral Sclerosis Rehabilitation: Rationale, Feasibility and Potential Effectiveness of a Novel Rehabilitation Approach.

Primary lateral sclerosis (PLS) is an adult-onset idiopathic disorder of the upper motor neuron system. Robot-aided rehabilitation with the Lokomat-Pro (LT) allows maximizing motor training by finely and individually controlling motor activation. No data are currently available on the use of robot-aided rehabilitation in PLS. The aim of this case study was to evaluate the effectiveness of a customized robotic rehabilitation protocol in PLS. A 54-year-old woman, diagnosed with PLS five years before admission, came to our clinic to undergo rehabilitation training due to gait difficulties with spastic paraparesis. The patient was treated with two different approaches: conventional physiotherapy followed by a combined approach (i.e. PT plus LT). After the conventional PT rehabilitation, no significant functional improvement was noted. However, the combined approach led to a significant improvement in functional motor skills, including walking, balance and lower limb muscle strength, and spasticity. Our experimental training combining robot-aided and conventional rehabilitation could be a promising approach to mitigate the PLS disability burden.

Base-peak assessment of levodopa response and detection of fluctuating patients in Parkinson's disease.

OBJECTIVES: This study aims to evaluate the base-peak difference in levodopa response for detecting patients with motor fluctuations in Parkinson's disease (PD). METHODS: Two independent PD samples were evaluated at baseline and 2 h after the administration of the usual morning dose of levodopa using the Unified Parkinson's Disease Rating Scale part III (UPDRS-III). The presence of motor fluctuations was defined by the UPDRS-IV. We quantified the magnitude of motor variation as absolute (Δ) and percentage (Δ%) change in UPDRS-III scores. Optimal cut-offs for each index distinguishing patients with or without fluctuations were calculated on the exploratory population. The accuracy of the identified cut-offs was then verified in a testing population. RESULTS: In the exploratory population (N = 26), the optimal cut-off for detecting fluctuations was a Δ of 6 points and a Δ% of 18.4%. When we applied the identified thresholds to the testing population (N = 139), we found a sensitivity of 93.8% (95% CI: 89.7 to 97.8) and a specificity of 91.2% (95% CI: 86.5 to 95.9) for Δ, 83.3% (95% CI: 77.1 to 89.5) and 86.8% (95% CI: 81.2 to 92.4) for Δ%, respectively. CONCLUSIONS: The assessment of levodopa usual morning dose response through the base-peak evaluation represents an accurate method for detecting parkinsonian patients with motor fluctuations, and for defining the Minimal Important Difference (MID) in levodopa response suggesting the presence of motor fluctuations in PD patients demanding further therapeutic interventions.

Can volcanic trace elements facilitate Covid-19 diffusion? A hypothesis stemming from the Mount Etna area, Sicily.

In December 2019, severe cases of pneumonia of unknown aetiology were reported in Wuhan city, in China. Lately, the pneumonia was related to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and the diseases was termed coronavirus disease-2019 (COVID-19). At the end of January 2020, the infection spread all over Italy, but with high infection rates and mortality in the northern part, especially in Lombardy, the most industrialized and polluted region of the country. It is noteworthy that a strong association between severe viral respiratory disease and air pollution has been described. Air pollutant could be solid particles, liquid droplets, or gases and can be of natural origin (such as ash from a volcanic eruption) or released from motor vehicle depletes (carbon monoxide gas) or factories (sulfur dioxide). Volcanic eruptions release large amounts of sulphuric acid, hydrogen sulfide, and hydrochloric acid into the atmosphere. Pulmunary diseases spreadby means of small droplets in thebreath, also called aerosols, and air pollution may facilitate the outside survival of viruses. We suppose that ash and gases emitted from the Mount Etna contributed to air pollution, potentially favouring the major contagion of COVID-19 in the eastern flank of the mountain, as in Catania city. In fact, ash and gases (with regard to radon) are usually particularly intense in winter, with a reduction of emission of specific metals with warmer weather. This is the first paper that elaborates the hypothesis of a potential role of volcanic gases and heavy metals-related air pollution, combined to specific climatic conditions and regional topography, in favouring severe COVID-19 diffusion in Sicily. Clinical and epidemiological studies are needed to support the hypothesis and plan the due prevention and awareness-raising campaigns.

Sexual Dysfunction in Parkinson Disease: A Multicenter Italian Cross-sectional Study on a Still Overlooked Problem.

BACKGROUND: Prevalence rates of sexual dysfunction (SD) in Parkinson's disease (PD) are likely to be underestimated and their etiology is still unknown. More understanding of this issue is needed. AIM: To investigate prevalence of SD and its variables, including gender differences, in a sample of PD patients. METHODS: This multicenter observational study included 203 patients (113 males and 90 females) affected by PD (diagnosed according to UK Parkinson's Disease Society Brain Bank clinical diagnostic criteria 28), and living in 3 different Italian regions. Patients were evaluated using a semi-structured interview (a 40-item ad hoc questionnaire, developed by the authors to investigate patient's 3 main life areas: sociodemographic information, illness perception, and sexuality) and specific standardized scales to investigate SD, as well as by means of tools to assess their motor impairment, daily life activities, and disease-related caregiver burden (CBI). MAIN OUTCOME MEASURES: The International Index of Erectile Function and the Female Sexual Function Index. RESULTS: Sexual dysfunction was observed in about 68% of men, and in around 53% of women loss of libido being the main sexual concern in both sexes. Men were significantly more affected by SD than women (χ2 (1) = 4.34, P-value = .037), but no difference in the severity of the dysfunction emerged between genders. Around 85% of PD patients had a stable couple relationship, and about 40% were satisfied with such a relationship. However, about 57% of the patients stated that the disease affected their sexual life, especially due to reduced sexual desire, and the frequency of sexual intercourses. Moreover, significant differences between subjects with SD and subjects without SD were found in UPDRS (I-II-III domains), in Hamilton Depression Rating Scale and CBI scores. CLINICAL IMPLICATIONS: Clinicians dealing with PD should pay more attention to sexual issues, as discussing and treating sexual problems enters the framework of a holistic approach, which is mandatory in chronic illness. STRENGTHS & LIMITATIONS: The major strengths of this study include the multicenter nature of the study, to overcome single-center methodological bias. The main limitation is the relatively small sample size, and the absence of a control group, even if there are growing literature data on sexuality and aging supporting our findings. CONCLUSION: SD is a highly prevalent and devastating problem in patients affected by PD, negatively affecting their quality of life. Raciti L, De Cola MC, Ortelli P, et al. Sexual Dysfunction in Parkinson Disease: A Multicenter Italian Cross-sectional Study on a Still Overlooked Problem. J Sex Med 2020;17:1914-1925.

Specific Signatures of Serum miRNAs as Potential Biomarkers to Discriminate Clinically Similar Neurodegenerative and Vascular-Related Diseases.

Neurodegenerative diseases (NDs) are age-dependent; among them, Alzheimer's disease (AD) and Parkinson's disease (PD) are the most frequent. Similarly, cerebrovascular damage can induce the development of vascular-related disorders that share common features with AD and PD, respectively, named vascular dementia (VD) and vascular parkinsonism (VP). To date, ND diagnosis is mainly clinical; therefore, since these disorders show similar symptoms, their correct discrimination may be difficult. We detected 23 ND-associated microRNAs (miRNAs) by literature mining and investigated their serum expression in a cohort of 139 patients including AD, PD, VD, and VP patients and healthy controls. TaqMan RT-PCR data showed that miR-23a upregulation was associated with an ongoing neurodegenerative process, similar to miR-22* and miR-29a, while let-7d, miR-15b, miR-24, miR-142-3p, miR-181c, and miR-222 showed an altered expression in Parkinson-like phenotypes, as well as miR-34b, miR-125b, and miR-130b in Alzheimer-like disorders. By computing logistic regression models and ROC curves, we identified signatures of neuro-miRNAs specific for each disease, showing good diagnostic performance. Interestingly, we found that miR-23a, miR-29a, miR-34b, and miR-125b exhibited a different distribution between exosomes and vesicle-free serum, suggesting a heterogeneity of secretion for these miRNAs. Our results suggest that miRNA signatures could discriminate in a non-invasive manner neurodegenerative disorders, thus improving clinical diagnoses.

Cardiovascular autonomic function and MCI in Parkinson's disease.

INTRODUCTION: dysautonomic dysfunction and cognitive impairment represent the most disabling non-motor features of Parkinson's Disease (PD). Recent evidences suggest the association between Orthostatic Hypotension (OH) and PD-Dementia. However, little is known on the interactions between cardiovascular dysautonomia and Mild Cognitive Impairment (MCI). We aimed to evaluate the association between cardiovascular dysautonomia and MCI in patients with PD. METHODS: non-demented PD patients belonging to the PACOS cohort underwent a comprehensive instrumental neurovegetative assessment including the study of both parasympathetic and sympathetic function (30:15 ratio, Expiratory-Inspiratory ratio [E-I] and presence of Orthostatic Hypotension [OH]). Diagnosis of MCI was made according to the MDS criteria level II. RESULTS: we enrolled 185 PD patients of whom 102 (55.1%) were men, mean age was 64.6 ±â€¯9.7 years, mean disease duration of 5.6 ±â€¯5.5 years with a mean UPDRS-ME score of 31.7 ±â€¯10.9. MCI was diagnosed in 79 (42.7%) patients. OH was recorded in 52 (28.1%) patients, altered 30:15 ratio was recorded in 39 (24.1%) patients and an altered E-I ratio was found in 24 (19.1%) patients. Presence of MCI was associated with an altered 30:15 ratio (adjOR 2.83; 95%CI 1.25-6.40) but not with an altered E-I ratio, while OH was associated only with the amnestic MCI subgroup (OR 2.43; 95% CI 1.05-5.06). CONCLUSION: in our study sample, MCI was mainly associated with parasympathetic dysfunction in PD.

Accuracy of MDS-UPDRS section IV for detecting motor fluctuations in Parkinson's disease.

BACKGROUND: In a precedent paper, we validated part IV of the Unified Parkinson's Disease Rating Scale (UPDRS) for detecting motor fluctuations in Parkinson's Disease (PD) patients using a 12-h Waking-Day Motor Assessment (WDMA) as gold standard, showing a high sensitivity (> 80%) and a lower specificity (< 45%). The aim of this study was to validate the Movement Disorder Society-UPDRS (MDS-UPDRS) part IV, especially items 4.3 and 4.5, using the same methodology. METHODS: PD patients attending the Movement Disorders Clinic at the University Hospital in Catania were consecutively enrolled in the study. A diurnal WDMA was performed to detect motor fluctuations. At each time interval, the motor impairment was evaluated using the motor section of the MDS-UPDRS. Presence or absence of motor fluctuations and the type of motor fluctuation were assessed by four blinded expert raters in movement disorders, by evaluating the graphical representations of the WDMA. We evaluated sensitivity and specificity together with 95% Confidence Interval (CI) of items 4.3 and 4.5, using WDMA as gold standard. RESULTS: We estimated for item 4.3 of the MDS-UPDRS a sensitivity of 74.3% (95% CI 56.7-87.5) and a specificity of 70.6% (95% CI 44-89.7), while for item 4.5, a sensitivity of 67.9% (95% CI 47.6-84.1) and a specificity of 66.7% (95% CI 44.7-84.4). CONCLUSIONS: The present showed a higher specificity level for MDS-UPDRS with respect to the UPDRS, while a slightly lower sensitivity mainly for predictable OFF.