Long-Term Risk of Arterial Thrombosis After Intracerebral Hemorrhage: MUCH-Italy.

BACKGROUND: The identification of patients surviving an acute intracerebral hemorrhage who are at a long-term risk of arterial thrombosis is a poorly defined, crucial issue for clinicians. METHODS: In the setting of the MUCH-Italy (Multicenter Study on Cerebral Haemorrhage in Italy) prospective observational cohort, we enrolled and followed up consecutive 30-day intracerebral hemorrhage survivors to assess the long-term incidence of arterial thrombotic events, to assess the impact of clinical and radiological variables on the risk of these events, and to develop a tool for estimating such a risk at the individual level. Primary end point was a composite of ischemic stroke, myocardial infarction, or other arterial thrombotic events. A point-scoring system was generated by the ß-coefficients of the variables independently associated with the long-term risk of arterial thrombosis, and the predictive MUCH score was calculated as the sum of the weighted scores. RESULTS: Overall, 1729 patients (median follow-up time, 43 months [25th to 75th percentile, 69.0]) qualified for inclusion. Arterial thrombotic events occurred in 169 (9.7%) patients. Male sex, diabetes, hypercholesterolemia, atrial fibrillation, and personal history of coronary artery disease were associated with increased long-term risk of arterial thrombosis, whereas the use of statins and antithrombotic medications after the acute intracerebral hemorrhage was associated with a reduced risk. The area under the receiver operating characteristic curve of the MUCH score predictive validity was 0.716 (95% CI, 0.56-0.81) for the 0- to 1-year score, 0.672 (95% CI, 0.58-0.73) for the 0- to 5-year score, and 0.744 (95% CI, 0.65-0.81) for the 0- to 10-year score. C statistic for the prediction of events that occur from 0 to 10 years was 0.69 (95% CI, 0.64-0.74). CONCLUSIONS: Intracerebral hemorrhage survivors are at high long-term risk of arterial thrombosis. The MUCH score may serve as a simple tool for risk estimation.

Risk Profile of Patients with Spontaneous Cervical Artery Dissection.

OBJECTIVE: Epidemiological data to characterize the individual risk profile of patients with spontaneous cervical artery dissection (sCeAD) are rather inconsistent. METHODS AND RESULTS: In the setting of the Italian Project on Stroke in Young Adults Cervical Artery Dissection (IPSYS CeAD), we compared the characteristics of 1,468 patients with sCeAD (mean age = 47.3 ± 11.3 years, men = 56.7%) prospectively recruited at 39 Italian centers with those of 2 control groups, composed of (1) patients whose ischemic stroke was caused by mechanisms other than dissection (non-CeAD IS) selected from the prospective IPSYS registry and Brescia Stroke Registry and (2) stroke-free individuals selected from the staff members of participating hospitals, matched 1:1:1 by sex, age, and race. Compared to stroke-free subjects, patients with sCeAD were more likely to be hypertensive (odds ratio [OR] = 1.65, 95% confidence interval [CI] = 1.37-1.98), to have personal history of migraine with aura (OR = 2.45, 95% CI = 1.74-3.34), without aura (OR = 2.67, 95% CI = 2.15-3.32), and family history of vascular disease in first-degree relatives (OR = 1.69, 95% CI = 1.39-2.05), and less likely to be diabetic (OR = 0.65, 95% CI = 0.47-0.91), hypercholesterolemic (OR = 0.75, 95% CI = 0.62-0.91), and obese (OR = 0.41, 95% CI = 0.31-0.54). Migraine without aura was also associated with sCeAD (OR = 1.81, 95% CI = 1.47-2.22) in comparison with patients with non-CeAD IS. In the subgroup of patients with migraine, patients with sCeAD had higher frequency of migraine attacks and were less likely to take anti-migraine preventive medications, especially beta-blockers, compared with the other groups. INTERPRETATION: The risk of sCeAD is influenced by migraine, especially migraine without aura, more than by other factors, increases with increasing frequency of attacks, and seems to be reduced by migraine preventive medications, namely beta-blockers. ANN NEUROL 2023;94:585-595.

Statin use and long-term risk of recurrent intracerebral haemorrhage: the MUCH-Italy.

BACKGROUND: Whether statin use after spontaneous intracerebral haemorrhage (ICH) increases the risk of recurrent ICH is uncertain. METHODS: In the setting of the Multicentric Study on Cerebral Haemorrhage in Italy we followed up a cohort of 30-day ICH survivors, consecutively admitted from January 2002 to July 2014, to assess whether the use of statins after the acute event is associated with recurrent cerebral bleeding. RESULTS: 1623 patients (mean age, 73.9±10.3 years; males, 55.9%) qualified for the analysis. After a median follow-up of 40.5 months (25th to 75th percentile, 67.7) statin use was not associated with increased risk of recurrent ICH either in the whole study group (adjusted HR, 0.99; 95% CI 0.64 to 1.53) or in the subgroups defined by haematoma location (deep ICH, adjusted HR, 0.74; 95% CI 0.35 to 1.57; lobar ICH, adjusted HR, 1.09; 95% CI 0.62 to 1.90), intensity of statins (low-moderate intensity statins, adjusted HR, 0.93; 95% CI 0.58 to 1.49; high-intensity statins, adjusted HR, 1.48; 95% CI 0.66 to 3.31) and use of statins before the index event (adjusted HR, 0.66; 95% CI 0.38 to 1.17). CONCLUSIONS: Statin use appears to be unrelated to the risk of ICH recurrence.

Can mobile health apps with smartphones and tablets be the new frontier of cognitive rehabilitation in older individuals? A narrative review of a growing field.

INTRODUCTION: A recent interesting field of application of telemedicine/e-health involved smartphone apps. Although research on mHealth began in 2014, there are still few studies using these technologies in healthy elderly and in neurodegenerative disorders. Thus, the aim of the present review was to summarize current evidence on the usability and effectiveness of the use of mHealth in older adults and patients with neurodegenerative disorders. METHODS: This review was conducted by searching for recent peer-reviewed articles published between June 1, 2010 and March 2023 using the following databases: Pubmed, Embase, Cochrane Database, and Web of Science. After duplicate removal, abstract and title screening, 25 articles were included in the full-text assessment. RESULTS: Ten articles assessed the acceptance and usability, and 15 articles evaluated the efficacy of e-health in both older individuals and patients with neurodegenerative disorders. The majority of studies reported that mHealth training was well accepted by the users, and was able to stimulate cognitive abilities, such as processing speed, prospective and episodic memory, and executive functioning, making smartphones and tablets valuable tools to enhance cognitive performances. However, the studies are mainly case series, case-control, and in general small-scale studies and often without follow-up, and only a few RCTs have been published to date. CONCLUSIONS: Despite the great attention paid to mHealth in recent years, the evidence in the literature on their effectiveness is scarce and not comparable. Longitudinal RCTs are needed to evaluate the efficacy of mHealth cognitive rehabilitation in the elderly and in patients with neurodegenerative disorders.

A systematic review about the importance of neuropsychological features in heart failure: is at heart the only failure?

Heart failure can lead to cognitive impairment that is estimated to be present in over a quarter of patients. It is important to intervene at a cognitive level to promote brain plasticity through cognitive training programs. Interventions transformed by technology offer the promise of improved cognitive health for heart failure patients. This review was conducted on studies evaluating the role of cognitive rehabilitation in patients with heart failure. We examined clinical trials involving patients with heart failure. Our search was performed on Pubmed, Web of Science and Cochrane library databases. Of the initial 256 studies, 10 studies met the inclusion criteria. Cognitive rehabilitation training has important implications for the treatment and prevention of cognitive decline in heart failure patients with significant recovery for delayed recall memory and a significant time effect for total recall memory and delayed, psychomotor speed and IADL performance. It is important to include the assessment of cognitive functioning in the routine clinical examinations of patients with heart failure, discover the relationship between cognitive function and heart failure, and target cognitive rehabilitation programs that promote brain plasticity.

Understanding the family burden and caregiver role in stroke rehabilitation: insights from a retrospective study.

INTRODUCTION: Stroke negatively impacts both patients and their families, who must face multiple changes after the onset of the disease. Family caregivers must face new problems with a possible sense of inadequacy, stress and burden. Our retrospective study aimed to assess the burden of caregivers during the rehabilitation process of patients with Stroke. MATERIAL AND METHOD: This study included patients with a diagnosis of stroke and their caregiver, who attended the Day Hospital of the IRCCS Neurolesi Center "Bonino-Pulejo", Messina, Italy, between January 2018 and October 2019, using electronic recovery system data. The final sample consisted of 30 patients and their caregivers. RESULTS: Significant improvements were observed in patients' cognitive and mood scores, reflecting the efficacy of rehabilitation therapies. Additionally, a correlation emerged between patients' reported anxiety levels and caregivers' reported depression levels, highlighting a dynamic interaction between the emotional states of the two groups. CONCLUSION: The study highlights the intricate interplay between caregiver characteristics, patient outcomes, and family dynamics in the context of caregiving. Targeted interventions aimed at improving family resilience and coping mechanisms are crucial to optimizing the well-being of both caregivers and patients.

Smartphone-Based Cognitive Telerehabilitation: A Usability and Feasibility Study Focusing on Mild Cognitive Impairment.

The implementation of cognitive health apps in patients with mild cognitive impairment (MCI) is challenging because of their cognitive, age, and other clinical characteristics. In this project, we aimed to evaluate the usability and feasibility of the Rehastart app tested in MCI patients. Eighteen subjects affected by MCI due to neurodegenerative disorders (including Parkinson's disease, multiple sclerosis, and amnestic/multidomain MCI) and eighteen healthcare professionals were recruited to this study. Patients were registered on the app by clinicians and they were assigned a protocol of specific cognitive exercises. The recruitment was conducted in the period between March and June 2023. The trial testing of the app consisted of three sessions per week for three weeks, with each session lasting about 30 min. After three weeks, the participants as well as medical personnel were invited to rate the usability and feasibility of the Rehastart mobile application. The instruments employed to evaluate the usability and feasibility of the app were the System Usability Scale (SUS), The Intrinsic Motivation Inventory (IMI) and the Client Satisfaction Questionnaire (CSQ). We did not find statistically significant differences on the SUS (p = 0.07) between healthcare professionals and patients. In addition, we found promising results on subscales of the Intrinsic Motivation Inventory, suggesting high levels of interest and enjoyment when using the Rehastart app. Our study demonstrated that smartphone-based telerehabilitation could be a suitable tool for people with MCI due to neurodegenerative disorders, since the Rehastart app was easy to use and motivating for both patients and healthy people.

Brain Plasticity in Patients with Spinal Cord Injuries: A Systematic Review.

A spinal cord injury (SCI) causes changes in brain structure and brain function due to the direct effects of nerve damage, secondary mechanisms, and long-term effects of the injury, such as paralysis and neuropathic pain (NP). Recovery takes place over weeks to months, which is a time frame well beyond the duration of spinal shock and is the phase in which the spinal cord remains unstimulated below the level of injury and is associated with adaptations occurring throughout the nervous system, often referred to as neuronal plasticity. Such changes occur at different anatomical sites and also at different physiological and molecular biological levels. This review aims to investigate brain plasticity in patients with SCIs and its influence on the rehabilitation process. Studies were identified from an online search of the PubMed, Web of Science, and Scopus databases. Studies published between 2013 and 2023 were selected. This review has been registered on OSF under (n) 9QP45. We found that neuroplasticity can affect the sensory-motor network, and different protocols or rehabilitation interventions can activate this process in different ways. Exercise rehabilitation training in humans with SCIs can elicit white matter plasticity in the form of increased myelin water content. This review has demonstrated that SCI patients may experience plastic changes either spontaneously or as a result of specific neurorehabilitation training, which may lead to positive outcomes in functional recovery. Clinical and experimental evidence convincingly displays that plasticity occurs in the adult CNS through a variety of events following traumatic or non-traumatic SCI. Furthermore, efficacy-based, pharmacological, and genetic approaches, alone or in combination, are increasingly effective in promoting plasticity.

Psycho-Neuroendocrinology in the Rehabilitation Field: Focus on the Complex Interplay between Stress and Pain.

Chronic stress and chronic pain share neuro-anatomical, endocrinological, and biological features. However, stress prepares the body for challenging situations or mitigates tissue damage, while pain is an unpleasant sensation due to nociceptive receptor stimulation. When pain is chronic, it might lead to an allostatic overload in the body and brain due to the chronic dysregulation of the physiological systems that are normally involved in adapting to environmental challenges. Managing stress and chronic pain (CP) in neurorehabilitation presents a significant challenge for healthcare professionals and researchers, as there is no definitive and effective solution for these issues. Patients suffering from neurological disorders often complain of CP, which significantly reduces their quality of life. The aim of this narrative review is to examine the correlation between stress and pain and their potential negative impact on the rehabilitation process. Moreover, we described the most relevant interventions used to manage stress and pain in the neurological population. In conclusion, this review sheds light on the connection between chronic stress and chronic pain and their impact on the neurorehabilitation pathway. Our results emphasize the need for tailored rehabilitation protocols to effectively manage pain, improve treatment adherence, and ensure comprehensive patient care.

Consensus Paper: Ataxic Gait.

The aim of this consensus paper is to discuss the roles of the cerebellum in human gait, as well as its assessment and therapy. Cerebellar vermis is critical for postural control. The cerebellum ensures the mapping of sensory information into temporally relevant motor commands. Mental imagery of gait involves intrinsically connected fronto-parietal networks comprising the cerebellum. Muscular activities in cerebellar patients show impaired timing of discharges, affecting the patterning of the synergies subserving locomotion. Ataxia of stance/gait is amongst the first cerebellar deficits in cerebellar disorders such as degenerative ataxias and is a disabling symptom with a high risk of falls. Prolonged discharges and increased muscle coactivation may be related to compensatory mechanisms and enhanced body sway, respectively. Essential tremor is frequently associated with mild gait ataxia. There is growing evidence for an important role of the cerebellar cortex in the pathogenesis of essential tremor. In multiple sclerosis, balance and gait are affected due to cerebellar and spinal cord involvement, as a result of disseminated demyelination and neurodegeneration impairing proprioception. In orthostatic tremor, patients often show mild-to-moderate limb and gait ataxia. The tremor generator is likely located in the posterior fossa. Tandem gait is impaired in the early stages of cerebellar disorders and may be particularly useful in the evaluation of pre-ataxic stages of progressive ataxias. Impaired inter-joint coordination and enhanced variability of gait temporal and kinetic parameters can be grasped by wearable devices such as accelerometers. Kinect is a promising low cost technology to obtain reliable measurements and remote assessments of gait. Deep learning methods are being developed in order to help clinicians in the diagnosis and decision-making process. Locomotor adaptation is impaired in cerebellar patients. Coordinative training aims to improve the coordinative strategy and foot placements across strides, cerebellar patients benefiting from intense rehabilitation therapies. Robotic training is a promising approach to complement conventional rehabilitation and neuromodulation of the cerebellum. Wearable dynamic orthoses represent a potential aid to assist gait. The panel of experts agree that the understanding of the cerebellar contribution to gait control will lead to a better management of cerebellar ataxias in general and will likely contribute to use gait parameters as robust biomarkers of future clinical trials.

Behavioral scales variability in patients with prolonged disorders of consciousness.

BACKGROUND: The principal conditions differentiating disorders of consciousness (DOC) patients are the unresponsive wakefulness syndrome/vegetative state (UWS/VS) and the minimally conscious state (MCS). Many individuals who suffer from sudden-onset severe brain injury move through stages of UWS/VS and MCS before regaining full awareness. In some patients, the DOC condition is protracted for years (PDOC). In this study, we observed PDOC patients for 6 months to assess possible changes in their level of consciousness. METHODS: We enrolled 40 PDOC patients, 23 UWS/VS and 17 MCS hosted in a dedicated unit for long-term brain injury care. The time from injury was 472 ± 533 days for UWS/VS and 1090 ± 1079 days for MCS. The Wessex Head Injury Matrix (WHIM), Coma Recovery Scale-R (CRS-R), and Nociception Coma Scale were administered monthly for 6 months. RESULTS: During the period of assessment, the percentage of UWS/VS shifted from 58 to 45%, while for the MCS, from 42 to 55%. A positive correlation was found for the UWS/VS patients between the months of observation with the CRS-R total score and WHIM total numbers of behaviors (TNB). In the UWS/VS group, the CRS-R auditive and visual subscales correlated positively with the observation time. During the whole period of observation, 8 patients had constant CRS-R total scores while the WHIM TNB changed in 7 of them. CONCLUSION: Our findings demonstrated that the monthly assessment of PDOC by means of the CRS-R and WHIM was able to detect also subtle changes in consciousness level.

Benefits of Telerehabilitation for Patients With Severe Acquired Brain Injury: Promising Results From a Multicenter Randomized Controlled Trial Using Nonimmersive Virtual Reality.

BACKGROUND: In neurorehabilitation, the use of innovative technologies offers many opportunities to monitor and improve the health status of patients with severe acquired brain injury (SABI). Telerehabilitation allows for continuity of service through the entire rehabilitation cycle, including assessment, intervention, consultation, and education, affording early reintegration and positively enhancing the quality of life (QoL). OBJECTIVE: The main purpose of this multicenter randomized controlled trial was to test the effectiveness of advanced training provided using a nonimmersive virtual reality rehabilitation system (ie, the VRRS HomeKit device) in improving functional outcomes in patients with SABI. METHODS: In total, 40 patients with SABI and their 40 caregivers visiting 2 Italian rehabilitation centers were enrolled in the study protocol and randomized into 2 groups. Of the 40 patients, 20 (50%) underwent the experimental training using the VRRS HomeKit (teleneuro-VRRS group), whereas the other 20 (50%) were administered usual territorial rehabilitative treatments (UTRTs; control group). To investigate motor and neuropsychological functioning, patients with SABI were evaluated before (T0) and at the end of (T1) each training session by a multispecialist team through a complete clinical and psychometric battery: the Barthel Index (BI), the Tinetti Scale (TS), the Modified Ashworth Scale (MAS), the Montreal Cognitive Assessment (MoCa), the Frontal Assessment Battery (FAB), the Beck Depression Inventory II (BDI-II), the Short Form Health Survey 36 (SF-36), and the Psychological General Well-Being Index (PGWBI). In addition, the Caregiver Burden Inventory (CBI) was administered to each caregiver to investigate the emotional burden status. RESULTS: The teleneuro-VRRS group achieved a statistically significant improvement in both general and motor outcomes, as well as psychological well-being and QoL, compared to the control group. In particular, the BI (P<.001), FAB (P<.001), and BDI-II (P<.001) were the outcome scales with the best improvement. The burden of caregivers also significantly improved in the teleneuro-VRRS group (CBI; P<.004). Between-group analysis showed statistical differences in the anxiety (effect size [ES]=0.85, P<.02) and self-control (ES=0.40, P<.03) subtests of the PGWBI and in the social role functioning (ES=0.85, P<.02) subtest of the SF-36, confirmed by quite medium and large ESs. CONCLUSIONS: Our results suggest that the VRRS is a suitable alternative tool or complementary tool or both to improve motor (level of functional independence) and cognitive (frontal/executive abilities) outcomes, reducing behavioral alterations (anxiety and depression symptoms) in patients with SABI, with a beneficial impact also on the caregivers' burden distress management, mitigating distress and promoting positive aspects of caring. TRIAL REGISTRATION: ClinicalTrials.gov NCT03709875; https://classic.clinicaltrials.gov/ct2/show/NCT03709875.

Alzheimer cafè: toward bridging the gap between cure and care in patients with dementia.

BACKGROUND: Alzheimer's disease (AD) is the most common form of degenerative dementia, whose symptoms usually appear in the pre-senile age. In the early stages, patients present social difficulties due to the general cognitive decline in memory, language and executive domains. These problems also affect patients' quality of life, emotions, and mood, leading to social isolation. OBJECTIVE: The aim of this study is to evaluate the effects of Alzheimer's Cafè (AC) on the cognitive and behavioral outcomes of AD patients. METHODS: Twenty patients diagnosed with AD, who attended the Cognitive and Behavioral Rehabilitation Laboratory of the IRCCS Centro Neurolesi 'Bonino-Pulejo' of Messina, Italy, from December 2017 to December 2018, were enrolled in this study. As these patients belonged to the experimental group (EG: n = 20), they received specific cognitive-behavior training using the AC modality. The patients were assessed by a neuropsychological evaluation at the beginning and at the end of the program. Their outcomes were compared to a matched group of patients with neurodegenerative dementia (CG: 20) receiving conventional cognitive training. RESULTS: The pre-post comparisons showed that both CG and EG had a significant improvement in global cognitive functioning (MoCA p < 0.001) and in perceived quality of life (<0.001). However, only in the EG, we observed a significant increase in social functioning (SASS p < 0.00), the perception of mental well-being (SF-12 Mental p < 0.00), and a reduction in the depressive state (GDS p < 0.00). CONCLUSIONS: The present study suggests the importance of AC for patients with AD and the potential effect on psychological and social well-being.

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.

Sexual Dysfunctions in Females with Parkinson's Disease: A Cross-Sectional Study with a Psycho-Endocrinological Perspective.

Background and Objectives: Normal human sexual functioning is a complex integration of an intact neuroanatomic substrate, vascular supply, a balanced hormonal profile, and a predominance of excitatory over inhibitory psychological mechanisms. However, sexual functioning in Parkinson's disease (PD) is often overlooked in clinical practice, especially in female patients. Materials and Methods: In this cross-sectional study, we have investigated the frequency of sexual dysfunction and the possible correlation with psycho-endocrinological factors in a sample of women with idiopathic PD. Patients were assessed using a semi-structured sexual interview, in addition to psychometric tools, including the Hamilton Rating Scale for Anxiety and for Depression and the Coping Orientation to the Problems Experiences-New Italian Version. Specific blood tests, including testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen E2, prolactin (PRL), and vitamin D3 were also evaluated. Results: Our results reported a statistical difference in sexual intercourse frequency before and after the onset of PD (p < 0.001). The percentage of women who complained about reduced sexual desire increased after diagnosis (52.7%) compared to the period before the onset of the illness (36.8%). The endocrinological profile in females with PD revealed statistically significant differences regarding testosterone (p < 0.0006), estradiol (p < 0.00), vitamin D3 (p < 0.006), and calcium (0.002). Depression (44% characterized by perceived feelings of anger and frustration during sexual intercourse) and anxiety symptoms (29.5% reported feelings of fear and anxiety for not satisfying the partner) with abnormal coping strategies (48.14% experienced feelings of anger and intolerance) were also found to be statistically significant. This study showed a high frequency of sexual dysfunction in female patients with PD, which correlated with sexual hormone abnormalities, mood/anxiety, and coping strategies alterations. This supports the idea that there is a need to better investigate the sexual function of female patients with PD to provide them with an adequate therapeutic approach and potentially improve quality of life.

Antithrombotic therapy in the postacute phase of cervical artery dissection: the Italian Project on Stroke in Young Adults Cervical Artery Dissection.

OBJECTIVE: To explore the impact of antithrombotic therapy discontinuation in the postacute phase of cervical artery dissection (CeAD) on the mid-term outcome of these patients. METHODS: In a cohort of consecutive patients with first-ever CeAD, enrolled in the setting of the multicentre Italian Project on Stroke in Young Adults Cervical Artery Dissection, we compared postacute (beyond 6 months since the index CeAD) outcomes between patients who discontinued antithrombotic therapy and patients who continued taking antithrombotic agents during follow-up. Primary outcome was a composite of ischaemic stroke and transient ischaemic attack. Secondary outcomes were (1) Brain ischaemia ipsilateral to the dissected vessel and (2) Recurrent CeAD. Associations with the outcome of interest were assessed by the propensity score (PS) method. RESULTS: Of the 1390 patients whose data were available for the outcome analysis (median follow-up time in patients who did not experience outcome events, 36.0 months (25th-75th percentile, 62.0)), 201 (14.4%) discontinued antithrombotic treatment. Primary outcome occurred in 48 patients in the postacute phase of CeAD. In PS-matched samples (201 vs 201), the incidence of primary outcomes among patients taking antithrombotics was comparable with that among patients who discontinued antithrombotics during follow-up (5.0% vs 4.5%; p(log rank test)=0.526), and so was the incidence of the secondary outcomes ipsilateral brain ischaemia (4.5% vs 2.5%; p(log rank test)=0.132) and recurrent CeAD (1.0% vs 1.5%; p(log rank test)=0.798). CONCLUSIONS: Discontinuation of antithrombotic therapy in the postacute phase of CeAD does not appear to increase the risk of brain ischaemia during follow-up.

Applications of transcranial magnetic stimulation in migraine: evidence from a scoping review.

Transcranial magnetic stimulation (TMS), a non-invasive brain stimulation method, is trying to emerge as a migraine management strategy for both attack treatment and prevention. This scoping review presents 16 among single-pulse (to manage episodic and chronic migraine) and repetitive TMS randomized clinical trials (to manage chronic migraine). The works we reviewed suggest that TMS may be adopted as add-on therapy in those patients who are refractory to pharmacological therapy only with special arrangements for individualized treatment strategies or research. There are still limited clinical research programs and metaanalysis to promote routinely TMS employment, as TMS has been shown either to have no significant effects for any outcome or to be effective for migraine. These diverging conclusions depend on several biasing factors, including the lack of reliable, large, sham-controlled clinical trials, the dyshomogeneity in study designs (including the area of stimulation, the frequency of stimulation, the number of pulses, pulse intensity, and the number of sessions), patient selection criteria (migraine w/o aura, episodic and chronic migraine; TMS contraindication), and the lack of outcomes homogeneity and long-term real-world efficacy data. Therefore, in the future, it will be important to conduct larger randomized trials to confirm TMS usefulness in migraine management (acute attack and prophylactic treatment), identify those patients who may benefit from TMS, maybe independently of pharmacological treatments (i.e., using TMS as an alternative and not only as an add-on treatment). Otherwise, TMS will play a role in treating migraine only with special arrangements for individualized management strategies or research.

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.

Feasibility and usability of a non-immersive virtual reality tele-cognitive app in cognitive rehabilitation of patients affected by Parkinson's disease.

BACKGROUND: Cognitive impairment is one of the most common non-motor features of Parkinson's disease (PD). The aim of the present study was to evaluate the feasibility and acceptability/usability of a protocol using a non-immersive virtual reality tele-cognitive app, performed remotely in a sample of Italian patients with PD. METHODS: Non-demented patients with mild PD were included in the study. Patients performed the cognitive rehabilitation in a remote way, at home (three training sessions lasting 20 min/week for 6 weeks) using the NeuroNation app, downloaded for free on the patients' smartphones. The usability and feasibility of the tele-cognitive rehabilitation program were assessed with the System Usability Scale (SUS) and the Goal Attainment Scaling (GAS). RESULTS: Sixteen patients (9 men and 7 women; mean age 58.4 ± 8.3 years; mean disease duration 4.6 ± 2.1 years) were included in the study. At the end of the study, the mean SUS was 83.4 ± 11.5. The GAS score recorded at the end of the study (65.6 ± 4.2) was significantly higher than at baseline (38.5 ± 2.4; P-value <0.001). CONCLUSION: In our sample, good feasibility and usability were observed for a 6-week cognitive rehabilitation protocol based on the non-immersive virtual reality tele-cognitive app NeuroNation. Our data support the usefulness of cognitive rehabilitation performed in a remote way in PD patients.

Is psychosocial rehabilitation useful in older people living in nursing homes? A pilot study on long-term cognitive and behavioural outcomes.

BACKGROUND: Age-related changes in cognitive and behavioural functions, although common, may vary considerably across individuals and cognitive domains. There is limited evidence focusing on the benefits of training based on cognitive/social learning principles in the elderly. The aim of this study is to investigate the effects of Assertive Social Skill Training (ASST) in improving cognitive and mood outcomes in a sample of older patients living in a Sicilian nursing home. METHODS: Forty-seven older subjects were enrolled in this case-control study. Each participant was evaluated by a neuropsychologist, through the administration of a short psychometric battery using the Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), and Geriatric Depression Scale (GDS), at three time points: before (T0), immediately following (T1), and 6 months after the end of the training (T2). Both groups received cognitive behavioural therapy and psychological support, but the experimental group received the ASST protocol (60 sessions, five times a week, for 12 weeks, each session lasting about 60 min), whilst the control group participated in group meetings with recreational activities. RESULTS: Post-hoc analysis showed that only patients receiving ASST presented a statistically significant improvement in global cognitive functions (MMSE: P < 0.001), frontal abilities (FAB: P < 0.001), and mood (GDS: P < 0.001); these positive outcomes were maintained at T2. CONCLUSIONS: Promising treatments, like the ASST, aimed at potentiating cognitive, behavioural, and social skills, are needed to improve older people's quality of life, especially when they live in nursing homes.