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Introduction Neurological sequelae following SARS-CoV-2 infection still represent a serious concern both for neurologists and neuroscientists. In our paper, we investigated pain, myalgia, and fatigue as symptoms in long-COVID patients with an electrophysiological approach, comprising the evaluation of sympathetic skin responses (SSRs) and quantitative electromyography (qEMG). Materials and methods Twelve patients were enrolled (mean age, 47.7 ± 11.6 years), referred to our attention because of myalgia, pain, or muscle cramps, which persisted about 6 months after the diagnosis of SARS-CoV-2 infection. They underwent conventional electroneurography (ENG), needle electromyography (EMG), and SSRs; moreover, qEMG was performed by sampling at least 20 motor unit potentials (20–30 MUPs) during weak voluntary contraction in deltoid and tibialis anterior muscles. The mean duration, amplitude, and percentage of polyphasic potentials were assessed and compared with healthy and age-matched volunteers. Results ENG did not disclose significant changes compared to healthy subjects; needle EMG did not reveal denervation activity. In addition, qEMG showed MUPs similar to those recorded in healthy volunteers in terms of polyphasia (deltoid: p = 0.24; TA: p = 0.35), MUP area (deltoid: p = 0.45; TA: p = 0.44), mean duration (deltoid: p = 0.06; TA: p = 0.45), and amplitude (deltoid: p = 0.27; TA: p = 0.63). SSRs were not recordable from lower limbs in seven patients (58%) and from the upper ones in three of them (25%). Conclusion Our data suggest an involvement of the autonomic system, with a focus on cholinergic efferent sympathetic activity, without any evidence of myopathic changes.

Objective The role of motor cortex reorganization in the development and maintenance of phantom limb pain (PLP) is still unclear. This study aims to evaluate neurophysiological and structural motor cortex asymmetry in patients with PLP and its relationship with pain intensity. Methods Cross-sectional analysis of an ongoing randomized-controlled trial. We evaluated the motor cortex asymmetry through two techniques: i) changes in cortical excitability indexed by transcranial magnetic stimulation (motor evoked potential, paired-pulse paradigms and cortical mapping), and ii) voxel-wise grey matter asymmetry analysis by brain magnetic resonance imaging. Results We included 62 unilateral traumatic lower limb amputees with a mean PLP of 5.9 (SD = 1.79). We found, in the affected hemisphere, an anterior shift of the hand area center of gravity (23 mm, 95% CI 6 to 38, p = 0.005) and a disorganized and widespread representation. Regarding voxel-wise grey matter asymmetry analysis, data from 21 participants show a loss of grey matter volume in the motor area of the affected hemisphere. This asymmetry seems negatively associated with time since amputation. For TMS data, only the ICF ratio is negatively correlated with PLP intensity (r = −0.25, p = 0.04). Conclusion There is an asymmetrical reorganization of the motor cortex in patients with PLP, characterized by a disorganized, widespread, and shifted hand cortical representation and a loss in grey matter volume in the affected hemisphere. This reorganization seems to reduce across time since amputation. However, it is not associated with pain intensity. Significance These findings are significant to understand the role of the motor cortex reorganization in patients with PLP, showing that the pain intensity may be related with other neurophysiological factors, not just cortical reorganization.

Introduction: Primary dysmenorrhea affects many women, being a major cause of absenteeism and reduced productivity at work and at school. Although non-steroidal anti-inflammatory drugs (NSAIDs) are a good treatment option, up to 18% of women show no response or present allergic reactions and adverse events. Curcumin has antispasmodic, antinociceptive, and both specific and nonspecific anti-inflammatory effects, with good tolerability and safety. To date, no previous trial involving curcumin and dysmenorrhea pain has been performed. Therefore, our main goal is to assess the efficacy of curcumin for pain relief among women with primary dysmenorrhea, along with determining curcumin’s adverse effects and tolerability profile.Methods: A phase II, single-center, randomized, triple-blinded, placebo-controlled, parallel-group, superiority trial to evaluate the effect of curcumin (500 mg/12h) in pain reduction in women (18 to 35-year-old) with primary dysmenorrhea. A first cycle will be used for a passive, observational run-in phase. A sample of 108 participants (54 per group) is necessary to detect a 30% difference in pain sensitivity between groups assessed by visual analogue scale (VAS). Secondary outcomes include side effects, Cox Menstrual Symptom Scale (CMSS), and use of rescue drugs for pain relief. Discussion: Clinical evidence has shown analgesic and anti-inflammatory effects of curcumin and in view of dysmenorrhea’s physiopathology being related to those mechanisms targeted by curcumin, we hypothesize its use could represent an innovative and effective therapy to reduce the severity of this disease and its symptoms. Keywords: primary dysmenorrhea, Curcumin, pain relief, Visual Analogue Scale, Cox Menstrual Symptom Scale.

Background The analgesic effects of transcranial Direct Current Stimulation (tDCS) combined with physical therapy remain unclear. Objective To systematically review available evidence comparing tDCS with any physical therapy modality (PTM) to PTM alone or PTM with sham tDCS on pain relief on common musculoskeletal (MSK) conditions, namely knee osteoarthritis (KOA), chronic low back pain (CLBP), myofascial pain syndrome (MPS) and fibromyalgia. Methods EMBASE and MEDLINE were searched from inception to April 2019 for randomized controlled trials. Reviewers independently assessed the studies quality and extracted data according to the PRISMA protocol. The GRADE approach was used to asses quality of evidence and a "Summary of Findings" table was created. The analyses used random-effects model. The primary outcome was pain reduction after treatment. Results Eight articles were included. Only one study had low risk of bias. Quality of evidence was considered low or very low. Significant reduction in pain scores were found for fibromyalgia and KOA (Standardized mean difference (SMD) = -1.94 [95% CI: -3.37 to -0.49; I 2=76.4%] and SMD = -2.35 [95% CI: -3.63 to -1.06; I 2=69.7%] respectively). Subgroup analysis considering the type of PTM despite MSK condition revealed significant reduction in pain scores for exercise, SMD = -1.20 [95% CI: -1.683 to -0.717; I 2=10.8%]. Conclusions Large heterogeneity and low quality of evidence and limited number of studies were found. Results suggest a potential analgesic effect of tDCS in combination with a PTM for fibromyalgia and KOA. Subgroup analysis suggests a stronger effect of tDCS when combined with an exercise based PTM.

In recent years, a growing body of literature has investigated the use of non-invasive brain stimulation (NIBS) techniques to influence cerebellar activity and the effects of cerebellar stimulation on other brain regions through its multiple complex projections. From the early 1990s, with the discovery of the so-called cerebellar inhibition (CBI), several studies have focused their attention on the use of cerebellar NIBS as treatment for different motor disorders. Cerebellar ataxias (CAs) represent the prototypical clinical manifestation of cerebellar alterations, but other movement disorders, such as Parkinson's disease, essential tremor, and dystonia have also been associated with alterations of networks which include the cerebellum, or of the cerebellum itself. Cerebellar transcranial direct current stimulation (ctDCS) could indeed represent an economical, non-invasive therapeutic tool with minimal side effects, thus improving the clinical management of patients and their quality of life. Studies show that ctDCS is effective as a therapeutic option for motor symptoms in patients with CAs, and especially in those with less severe forms, suggesting that ctDCS efficacy could result from augmented neuronal compensation, which itself relies on preserved cerebellar volume. Evidence for the efficacy of ctDCS is less conclusive for the other aforementioned motor disorders, although preliminary results are promising. Future studies should adopt more rigorous methods (e.g., larger sample sizes, double blinding, better characterization of the sample, reliable biomarkers), in order to allow the scientific community to derive higher-quality evidence on the efficacy of ctDCS as a therapeutic option for motor disorders.

The cerebellum is involved in multiple closed-loops circuitry which connect the cerebellar modules with the motor cortex, prefrontal, temporal, and parietal cortical areas, and contribute to motor control, cognitive processes, emotional processing, and behavior. Among them, the cerebello-thalamo-cortical pathway represents the anatomical substratum of cerebellum-motor cortex inhibition (CBI). However, the cerebellum is also connected with basal ganglia by disynaptic pathways, and cerebellar involvement in disorders commonly associated with basal ganglia dysfunction (e.g., Parkinson’s disease and dystonia) has been suggested. Lately, cerebellar activity has been targeted by non-invasive brain stimulation (NIBS) techniques including transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) to indirectly affect and tune dysfunctional circuitry in the brain. Although the results are promising, several questions remain still unsolved. Here, a panel of experts from different specialties (neurophysiology, neurology, neurosurgery, neuropsychology) reviews the current results on cerebellar NIBS with the aim to derive the future steps and directions needed. We discuss the effects of TMS in the field of cerebellar neurophysiology, the potentials of cerebellar tDCS, the role of animal models in cerebellar NIBS applications, and the possible application of cerebellar NIBS in motor learning, stroke recovery, speech and language functions, neuropsychiatric and movement disorders.

Deep brain stimulation is an established technique for the treatment of movement disorders related to neurodegenerative diseases such as Parkinson's disease (PD) and essential tremor (ET). Its application seems also feasible for the treatment of neuropsychiatric disorders such as treatment resistant depression (TRD) and Tourette's syndrome (TS). In a typical deep brain stimulation system, the amount of current delivered to the patients is constant and regulated by the physician. Conversely, an adaptive deep brain stimulation system (aDBS) is a closed loop system that adjusts the stimulation parameters according to biomarkers which reflect the patient's clinical state. In this chapter, we examined the main issues related to aDBS systems, which are both clinical and technological in nature. From a clinical point of view, we have reported the major findings related to symptoms management using aDBS and principal findings in animal models, showing that the implementation of closed loop adaptive deep brain stimulation can ameliorate symptom management in neurodegenerative disorders. From the technological point of view, we reported the major advances related to aDBS system design and implementation, such as noise filtering methods, biomarkers recording and processing to adjust pulse delivery. To date, aDBS systems represent a major evolution in brain stimulation, further developments are needed to maximize the efficacy of this technique and to expand its use in a wide range of neuropsychiatric disorders.

Deep brain stimulation is an established technique for the treatment of movement disorders related to neurodegenerative diseases such as Parkinson's disease (PD) and essential tremor (ET). Its application seems also feasible for the treatment of neuropsychiatric disorders such as treatment resistant depression (TRD) and Tourette's syndrome (TS). In a typical deep brain stimulation system, the amount of current delivered to the patients is constant and regulated by the physician. Conversely, an adaptive deep brain stimulation system (aDBS) is a closed loop system that adjusts the stimulation parameters according to biomarkers which reflect the patient's clinical state. In this chapter, we examined the main issues related to aDBS systems, which are both clinical and technological in nature. From a clinical point of view, we have reported the major findings related to symptoms management using aDBS and principal findings in animal models, showing that the implementation of closed loop adaptive deep brain stimulation can ameliorate symptom management in neurodegenerative disorders. From the technological point of view, we reported the major advances related to aDBS system design and implementation, such as noise filtering methods, biomarkers recording and processing to adjust pulse delivery. To date, aDBS systems represent a major evolution in brain stimulation, further developments are needed to maximize the efficacy of this technique and to expand its use in a wide range of neuropsychiatric disorders.

Background The application of stimulators implanted directly over deep brain structures (i.e., deep brain stimulation, DBS) was developed in the late 1980s and has since become a mainstream option to treat several neurological conditions. Conventional DBS involves the continuous stimulation of the target structure, which is an approach that cannot adapt to patients’ changing symptoms or functional status in real-time. At the beginning of 2000, a more sophisticated form of stimulation was conceived to overcome these limitations. Adaptive deep brain stimulation (aDBS) employs on-demand, contingency-based stimulation to stimulate only when needed. So far, aDBS has been tested in several pathological conditions in animal and human models. Objective To review the current findings obtained from application of aDBS to animal and human models that highlights effects on motor, cognitive and psychiatric behaviors. Findings while aDBS has shown promising results in the treatment of Parkinson's disease and essential tremor, the possibility of its use in less common DBS indications, such as cognitive and psychiatric disorders (Alzheimer's disease, obsessive-compulsive disorder, post-traumatic stress disorder) is still challenging. Conclusions While aDBS seems to be effective to treat movement disorders (Parkinson's disease and essential tremor), its role in cognitive and psychiatric disorders is to be determined, although neurophysiological assumptions are promising.

Objective. Adaptive deep brain stimulation (aDBS) is a form of invasive stimulation that was conceived to overcome the technical limitations of traditional DBS, which delivers continuous stimulation of the target structure without considering patients’ symptoms or status in real-time. Instead, aDBS delivers on-demand, contingency-based stimulation. So far, aDBS has been tested in several neurological conditions, and will be soon extensively studied to translate it into clinical practice. However, an exhaustive description of technical aspects is still missing. Approach. in this topical review, we summarize the knowledge about the current (and future) aDBS approach and control algorithms to deliver the stimulation, as reference for a deeper undestending of aDBS model. Main results. We discuss the conceptual and functional model of aDBS, which is based on the sensing module (that assesses the feedback variable), the control module (which interpretes the variable and elaborates the new stimulation parameters), and the stimulation module (that controls the delivery of stimulation), considering both the historical perspective and the state-of-the-art of available biomarkers. Significance. aDBS modulates neuronal circuits based on clinically relevant biofeedback signals in real-time. First developed in the mid-2000s, many groups have worked on improving closed-loop DBS technology. The field is now at a point in conducting large-scale randomized clinical trials to translate aDBS into clinical practice. As we move towards implanting brain-computer interfaces in patients, it will be important to understand the technical aspects of aDBS.

Background. The novel coronavirus (SARS-COV-2) and related syndrome (COVID-19) has required a worldwide measure of quarantine with severe consequences for millions of people. Methods. Since psychopathological consequences related to social restrictions have been reported, a systematic review according to Cochrane Collaboration guidelines and the PRISMA Statement was performed to quantify the effects of quarantine on mental health of adults. Major databases - Pubmed, Scopus, Embase, PsycInfo, and Web of Science- were researched for observational studies with data on mental health indexes related to quarantine or isolation for epidemic infections. Results. Twenty-one independent studies were included for 82,312 subjects. Conclusions. The results showed that at least 20% of people exposed to these conditions reported a psychological distress, with a prevalence of PTSD, depression and, less often, generalized anxiety. Important methodological bias weakens the conclusion of most studies, opening to the need of further research on mental health after quarantine and related risk/buffering factors.