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.

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.

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.