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.

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.

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.

Objective evaluation of Nintendo Wii Fit Plus balance program training on postural stability in Multiple Sclerosis patients: a pilot study.

The use of the Nintendo Wii system has become a common tool for balance rehabilitation in patients with multiple sclerosis, but few studies verified the effectiveness of such an approach using quantitative measures of postural control. We aimed to evaluate the impact of rehabilitation treatment using the Nintendo Wii Fit Plus balance program on objective stabilometric parameters in multiple sclerosis patients. We enrolled 36 multiple sclerosis patients, with mild-moderate disability, referring to the multiple sclerosis Centre of the University of Catania from September 2013 to June 2014. Twenty participants underwent 20 individual sessions of balance exercise using the Nintendo Wii Fit Plus. They were assessed at baseline (T0) and at the end of rehabilitation program (T1) by Neurocom Balance Manager. Functional independence measure, Barthel index, and Berg balance scale were also administered. At T1, we found a significant improvement in total path length-open eyes, sway area-open eyes, and mean sway velocity-open eyes. Patients showed significant improvement in functional independence measure motor score, Barthel index, and in Berg balance scale. No significant differences between T0 and T1 in closed eyes trials were found. A significant correlation between delta values between T0 and T1 of sway area-open eyes and the Berg balance scale (r = -0.76; P < 0.0001) was found. This study confirmed that balance rehabilitation training performed using the Nintendo Wii with balance board significantly reduced some postural sway parameters in multiple sclerosis patients. It could be a good support to standard rehabilitation program in multiple sclerosis patients.