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.

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.

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.

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.

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.