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.

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.

Does cybersickness affect virtual reality training using the Computer Assisted Rehabilitation Environment (CAREN)? Preliminary results from a case-control study in Parkinson's disease.

INTRODUCTION AND OBJECTIVE: This pilot study aimed to evaluate whether and to what extent cybersickness (CS) may affect a rehabilitation program using the Computer-assisted Rehabilitation Environment (CAREN), a virtual reality (VR) computer-assisted device for clinical rehabilitation. METHODS: The study was carried out on 30 subjects, 15 patients with Parkinson's Disease (PD) and 15 healthy controls (HC), which underwent a set of four exergames programmed by our team for PD rehabilitation training. RESULTS: All participants completed the Motion Sickness Susceptibility Questionnaire Short-form (MSSQ) before the training and the Motion Symptoms Assessment Questionnaire (MSAQ) immediately after a single CAREN session. Overall, mean MSAQ scores remained low after the session, suggesting that the users did not experience severe discomfort. We found no significant difference in MSAQ scores between the two groups, while there was a statistically significant difference for the subsection of MSAQ regarding the peripheral symptoms (i.e. sweating, cold sweating, feeling warm), which were higher in HC. Moreover, the results highlighted some correlation between MSSQ and MSAQ. Gastrointestinal symptoms in PD, as well as MSSQ and sopite-related symptoms in HC, were also correlated with susceptibility to CS. CONCLUSIONS: As CS is rarely reported after CAREN, this and similar devices may be considered comfortable and safe for patients' rehabilitation involving VR training, including PD persons.

How COVID-19 Has Affected Caregivers' Burden of Patients with Dementia: An Exploratory Study Focusing on Coping Strategies and Quality of Life during the Lockdown.

COVID-19 has caused a public and international health emergency, leading to isolation and social distancing. These restrictions have had a significant impact on the caregivers of people with dementia, increasing the burden of patient management. The purpose of this study was to investigate the stress perceived by caregivers of patients with Alzheimer's disease (AD) during the pandemic. We used a cross-sectional survey design to evaluate the caregivers' psychological responses and coping strategies. Eighty-four caregivers of patients with a diagnosis of AD were involved in this study by completing an online questionnaire. They presented a high perception of stress (the Perceived Stress Scale mean ± DS: 33.5 ± 4.5), and their high burden in caring was mainly related to physical difficulties (Caregiver Burden Inventory-Physical Burden mean ± DS: 15.0 ± 2.1) and perception of loss of time (Caregiver Burden Inventory-Time-dependence Burden mean ± DS: 16.5 ± 1.4). Moreover, caregivers perceived their quality of life as very low (Short Form-12 Health Survey Physical mean ± DS: 13.5 ± 2.7; Short Form-12 Health Survey Mental Health mean ± DS: 16.4 ± 4.2). Finally, we found that participants mostly used dysfunctional coping strategies, such as avoidance strategies (Coping Orientation to Problem Experiences-Avoidance Strategies mean ± DS: 39.5 ± 7.1), but these strategies did not affect the stress level of caregivers. Given that caregivers present a high burden and stress, innovative tools could be a valuable solution to investigate and support their emotional and behavioral status during difficult periods, such as the COVID-19 pandemic.

A dental implant dislocated in the ethmoidal sinus: A case report.

Maxillary sinusitis can represent a rare complication of dental implants of endodontic materials impinging in the maxillary sinuses. The effects of anatomical variants of paranasal sinuses on pathophysiological and clinical manifestations of dental sinusitis are poorly understood. Herein, we present a case of dislocation of a dental implant in the ethmoidal sinus in a 63-years old man with bilateral accessory maxillary orifice. This anatomical variation, by providing an additional way for the drainage of mucus in the maxillary sinus, could have allowed the dislocation of the implant in the ethmoidal sinus without causing mucus stagnation and consequent sinusitis, leading to a unusual clinical presentation. .

Toward Improving Diagnostic Strategies in Chronic Disorders of Consciousness: An Overview on the (Re-)Emergent Role of Neurophysiology.

The differential diagnosis of patients with Disorder of Consciousness (DoC), in particular in the chronic phase, is significantly difficult. Actually, about 40% of patients with unresponsive wakefulness syndrome (UWS) and the minimally conscious state (MCS) are misdiagnosed. Indeed, only advanced paraclinical approaches, including advanced EEG analyses, can allow achieving a more reliable diagnosis, that is, discovering residual traces of awareness in patients with UWS (namely, functional Locked-In Syndrome (fLIS)). These approaches aim at capturing the residual brain network models, at rest or that may be activated in response to relevant stimuli, which may be appropriate for awareness to emerge (despite their insufficiency to generate purposeful motor behaviors). For this, different brain network models have been studied in patients with DoC by using sensory stimuli (i.e., passive tasks), probing response to commands (i.e., active tasks), and during resting-state. Since it can be difficult for patients with DoC to perform even simple active tasks, this scoping review aims at summarizing the current, innovative neurophysiological examination methods in resting state/passive modality to differentiate and prognosticate patients with DoC. We conclude that the electrophysiologically-based diagnostic procedures represent an important resource for diagnosis, prognosis, and, therefore, management of patients with DoC, using advance passive and resting state paradigm analyses for the patients who lie in the "greyzones" between MCS, UWS, and fLIS.

Meralgia Paresthetica Successfully Treated with Palmithoylethanolamide.

Meralgia paresthetica (MP) is an uncommon entrapment mononeuropathy that is characterized by a sudden onset of paresthesia and numbness in the anterolateral surface of the thigh. Palmithoylethanolamide (PEA) is commonly used in the treatment of chronic pelvic pain and compressive neuropathies. Herein, we describe an otherwise healthy 28-year-old patient affected by posttraumatic MP for three months who was successfully treated with PEA (1200mg/day). Further studies are needed to better investigate the potential use of PEA as therapeutic drug in peripheral neuropathies, including MP, to avoid or delay more invasive surgical treatments.

Look at the cognitive deficits in patients with myotonic dystrophy type 1: an exploratory research on the effects of virtual reality.

Myotonic dystrophy type 1 is a neuromuscular disease, characterized by a progressive loss of strength, muscle stiffness, and difficulty in relaxation. Myotonic dystrophy type 1 patients can present several neuropsychological deficits, as well as anxiety and mood disorders. Aim of this study is to evaluate the feasibility and the effect of virtual reality in the cognitive and behavioral recovery of myotonic dystrophy type 1 patients. Eleven patients (8 female and 3 male) underwent a specific cognitive rehabilitation program including a conventional neuropsychological treatment followed by a virtual reality neurorehabilitation training using the Virtual Reality Rehabilitation System (Khymeia, Italy). Virtual reality improved many cognitive domains, including executive function, attention, verbal and visuo-spatial abilities, as well as mood and coping strategies. Due to the high prevalence of neuropsychological symptoms in patients with myotonic dystrophy type 1, cognitive rehabilitation should enter into the framework of these patients to potentially boost cognitive and behavioral function and improve quality of life.

Paving the way for a better understanding of the pathophysiology of gait impairment in myotonic dystrophy: a pilot study focusing on muscle networks.

BACKGROUND: A proper rehabilitation program targeting gait is mandatory to maintain the quality of life of patients with Myotonic dystrophy type 1 (DM1). Assuming that gait and balance impairment simply depend on the degree of muscle weakness is potentially misleading. In fact, the involvement of the Central Nervous System (CNS) in DM1 pathophysiology calls into account the deterioration of muscle coordination in gait impairment. Our study aimed at demonstrating the presence and role of muscle connectivity deterioration in patients with DM1 by a CNS perspective by investigating signal synergies using a time-frequency spectral coherence and multivariate analyses on lower limb muscles while walking upright. Further, we sought at determining whether muscle networks were abnormal secondarily to the muscle impairment or primarily to CNS damage (as DM1 is a multi-system disorder also involving the CNS). In other words, muscle network deterioration may depend on a weakening in signal synergies (that express the neural drive to muscles deduced from surface electromyography data). METHODS: Such an innovative approach to estimate muscle networks and signal synergies was carried out in seven patients with DM1 and ten healthy controls (HC). RESULTS: Patients with DM1 showed a commingling of low and high frequencies among muscle at both within- and between-limbs level, a weak direct neural coupling concerning inter-limb coordination, a modest network segregation, high integrative network properties, and an impoverishment in the available signal synergies, as compared to HCs. These network abnormalities were independent from muscle weakness and myotonia. CONCLUSIONS: Our results suggest that gait impairment in patients with DM1 depends also on a muscle network deterioration that is secondary to signal synergy deterioration (related to CNS impairment). This suggests that muscle network deterioration may be a primary trait of DM1 rather than a maladaptive mechanism to muscle degeneration. This information may be useful concerning the implementation of proper rehabilitative strategies in patients with DM1. It will be indeed necessary not only addressing muscle weakness but also gait-related muscle connectivity to improve functional ambulation in such patients.

Computer assisted cognitive rehabilitation improves visuospatial and executive functions in Parkinson's disease: Preliminary results.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disease due to dopamine deficiency in the basal ganglia, leading to motor symptoms such as bradykinesia, tremor, stiffness, and postural instability. This disease may also be associated with a broad spectrum of non-motor symptoms. More than 24% of patients with PD have one or more cognitive symptoms. OBJECTIVE: To evaluate the effects of computer-assisted cognitive rehabilitation (CACR) in Parkinson's disease (PD). METHODS: Sixty patients with PD were enrolled in this study and were randomly divided into control group (CG) and experimental group (EG). Each participant was evaluated at the beginning (T0) and at the end of training (T1). The CG underwent standard cognitive training (SCT) while EG performed CACR using the ERICA platform, aimed at improving several cognitive domains. In both the group, each training consisted of 3 sessions a week, each of these lasting sixty minutes, for eight weeks. RESULTS: Although both the groups had significant improvement after CR, we observed more significant changes in the EG, especially concerning attention, orientation and visual-spatial domains. CONCLUSIONS: Our data demonstrate that CACR is more effective than SCT in improving visual-spatial and executive deficits, in patients affected by PD.

Sexual dysfunction in male individuals with spinal cord iniury: What do we know so far?

AIM: The aim of this study is to define an overview of the impact of SCI on male sexuality and provide a framework for the pathophysiology and the treatment of sexual dysfunction in male with SCI. METHODS: This scoping review was conducted to identificate pathophysiology and the treatment of sexual dysfunction in SCI male. Studies were identified by searching on PubMed, Web Of Science and Cochrane databases during January 2010-July 2018. RESULTS: Despite sexual dysfunction in men with SCI varies due to complete or incomplete spinal injuries, treatment sexual intercourse should also be implemented in cases of paralysis and loss of sensitivity. This treatment should be integrated with the remaining sexual potential of the individual, based on rehabilitation programs. CONCLUSIONS: Our review suggests that it is necessary to increase knowledge about the management of sexual concerns in patients with SCI, representing an important aspect in the patient's family, social and emotional life.

Can Baropodometric Analysis be a Useful Tool in the Early Diagnosis of Atypical Parkinsonism? Preliminary Findings.

OBJECTIVE: The differential diagnosis between atypical parkinsonism and Parkinson's disease is difficult, especially in the early stage. Severe postural instability, falls, and complex gait impairments are usually confined to the later stage of Parkinson's disease, while atypical parkinsonism patients may present a severe postural instability with consequent falls in the earlier stages. METHODS: We retrospectively studied 20 subjects with parkinsonism using clinical and baropodometric tools to give quantitative and objective data on the postural, balance, and gait disturbances. RESULTS: The statistical analysis between atypical parkinsonism and Parkinson's disease patients showed a significant difference in the frequency of long lead time parameter, foot area, foot load and speed, and, in particular, atypical parkinsonism patients presented a prevalent long lead time impairment (8/8 patients) when compared with Parkinson's disease patients. DISCUSSION: Beside significant differences in the clinical features between the Parkinson's disease and atypical parkinsonism, our study showed that baropodometric investigation may a valuable tool for the definition of postural and motor extrapyramidal abnormalities, permitting an earlier differentiation between atypical parkinsonism and Parkinson's disease.

Ketotifen-induced nocturnal bruxism.

UNLABELLED: Nocturnal bruxism is a common oromandibular movement disorder highly prevalent in children, but its pathophysiological mechanism has not been fully explained. Iatrogenic sleep bruxism has been described following treatment with several psychotropic medications. However, no case of antihistamine-induced bruxism has been reported to date. Herein, we describe a 4-year-old child who experienced nocturnal bruxism during treatment for bronchospasm and rhinitis with the antihistamine ketotifen. Drug rechallenge was also performed. CONCLUSION: The present case adds useful information to our knowledge of bruxism. Complex and poorly understood interactions between multiple central nervous system neurotransmitters, such as histamine, serotonin, and dopamine, are involved.

Levetiracetam-associated loss of libido and anhedonia.

The relationship between the older antiepileptic drugs (AEDs) and sexual dysfunction has long been known and it is likely to be related to sexual hormonal changes. Instead, rare reports on sexual disorders related to new AEDs suggest the possibility of complex and poorly understood mechanisms, mainly involving central nervous system neurotransmitters such as glutamate, serotonin, and dopamine. Herein, we describe two young men with epilepsy who experienced severe loss of libido and anhedonia after levetiracetam intake.

Emerging role of PPAR-ß/δ in inflammatory process associated to experimental periodontitis.

The aim of the present study was to evaluate the contribution of peroxisome proliferator-activated receptor (PPAR-ß/δ) in animal model of periodontitis. Male Sprague-Dawley rats were lightly anaesthetized with pentobarbitone (35 mg/kg). Sterile, 2-0 black braided silk thread was placed around the cervix of the lower left first molar and knotted medially. Animals received GW0742 (0.3 mg/kg, 10% DMSO, i.p. after the ligature placement and daily for eight days). At day 8, the gingivomucosal tissue encircling the mandibular first molar was removed. One the eighth day after placement of the ligature, we evaluated (1) NF-κB expression, (2) cytokines expression, (3) iNOS expression, (5) the nitration of tyrosine, (6) apoptosis, and (8) the degree of gingivomucosal tissues injury. Administration of GW0742 significantly decreased all of the parameters of inflammation as described above. Taken together, these results demonstrate that GW0742 exerts an anti-inflammatory role during experimental periodontitis and is able to ameliorate the tissue damage.