Update on intensive motor training in spinocerebellar ataxia: time to move a step forward?:

Some evidence suggests that high-intensity motor training slows down the severity of spinocerebellar ataxia. However, whether all patients might benefit from these activities, and by which activity, and the underlying mechanisms remain unclear. We provide an update on the effect and limitations of different training programmes in patients with spinocerebellar ataxias. Overall, data converge of the finding that intensive training is still based either on conventional rehabilitation protocols or whole-body controlled videogames ("exergames"). Notwithstanding the limitations, short-term improvement is observed, which tends to be lost once the training is stopped. Exergames and virtual reality can ameliorate balance, coordination, and walking abilities, whereas the efficacy of adapted physical activity, gym, and postural exercises depends on the disease duration and severity. In conclusion, although a disease-modifying effect has not been demonstrated, constant, individually tailored, high-intensity motor training might be effective in patients with degenerative ataxia, even in those with severe disease. These approaches may enhance the remaining cerebellar circuitries or plastically induce compensatory networks. Further research is required to identify predictors of training success, such as the type and severity of ataxia and the level of residual functioning

A comprehensive review of transcranial magnetic stimulation in secondary dementia

Although primary degenerative diseases are the main cause of dementia, a non-negligible proportion of patients is affected by a secondary and potentially treatable cognitive disorder. Therefore, diagnostic tools able to early identify and monitor them and to predict the response to treatment are needed. Transcranial magnetic stimulation (TMS) is a non-invasive neurophysiological technique capable of evaluating in vivo and in "real time" the motor areas, the cortico-spinal tract, and the neurotransmission pathways in several neurological and neuropsychiatric disorders, including cognitive impairment and dementia. While consistent evidence has been accumulated for Alzheimer's disease, other degenerative cognitive disorders, and vascular dementia, to date a comprehensive review of TMS studies available in other secondary dementias is lacking. These conditions include, among others, normal-pressure hydrocephalus, multiple sclerosis, celiac disease and other immunologically mediated diseases, as well as a number of inflammatory, infective, metabolic, toxic, nutritional, endocrine, sleep-related, and rare genetic disorders. Overall, we observed that, while in degenerative dementia neurophysiological alterations might mirror specific, and possibly primary, neuropathological changes (and hence be used as early biomarkers), this pathogenic link appears to be weaker for most secondary forms of dementia, in which neurotransmitter dysfunction is more likely related to a systemic or diffuse neural damage. In these cases, therefore, an effort toward the understanding of pathological mechanisms of cognitive impairment should be made, also by investigating the relationship between functional alterations of brain circuits and the specific mechanisms of neuronal damage triggered by the causative disease. Neurophysiologically, although no distinctive TMS pattern can be identified that might be used to predict the occurrence or progression of cognitive decline in a specific condition, some TMS-associated measures of cortical function and plasticity (such as the short-latency afferent inhibition, the short-interval intracortical inhibition, and the cortical silent period) might add useful information in most of secondary dementia, especially in combination with suggestive clinical features and other diagnostic tests. The possibility to detect dysfunctional cortical circuits, to monitor the disease course, to probe the response to treatment, and to design novel neuromodulatory interventions in secondary dementia still represents a gap in the literature that needs to be explored

The severity of early fluid overload assessed by bioelectrical vector impedance as an independent risk factor for longer patient care after cardiac surgery

Background and aims: Fluid overload is a common postoperative complication in patients undergoing cardiac surgery. Although this condition is notably associated with relevant adverse outcomes, assessment of hydration status in clinical practice is challenging. Bioelectrical impedance vector analysis (BIVA) has emerged as a potentially effective method to monitor hydration changes, but the available evidence in critically ill patients undergoing cardiac surgery is limited and sometimes conflicting. The aim of this study was to explore by mean of BIVA the evolution over time of hydration status and its impact on relevant outcomes. Methods: Prospective observational study enrolling 130 patients undergoing cardiac surgery. Height normalized impedance was calculated both before surgery (baseline) and in the first five postoperative days. Relevant clinical and laboratory data were collected daily close to BIVA measurements. Length of mechanical ventilation (MV), intensive care unit (ICU) and hospital stay exceeding the 75th percentile of the study population were considered as study endpoints. Results: Compared to baseline, a significant reduction in impedance was found at first postoperative day, demonstrating a relevant fluid overload. An adjusted impedance at first postoperative day shorter than the best respective threshold was associated to longer MV (7.4 times), ICU stay (4.7 times) and hospital stay (5.6 times). A significant change in impedance and phase angle was documented throughout the observation days (p < 0.001), without returning to the baseline value. The co-existence of low impedance and high plasma osmolarity increased significantly the risk of incurring the study outcomes. Conclusions: In patients with cardiac surgery-induced fluid overload, recovery to baseline conditions occurs slowly. A relevant early fluid overload should be considered predictive for longer time of MV, ICU and total hospital stay

Post-stroke aphasia at the time of COVID-19 pandemic: a telerehabilitation perspective

We report on our remote speech therapy experience in post-stroke aphasia. The aim was to test the feasibility and utility of telerehabilitation to support future randomized controlled trials. Post-stroke aphasia is a common and disabling speech disorder, which significantly affects patients' and caregivers' health and quality of life. Due to COVID-19 pandemic, most of the conventional speech therapy approaches had to stop or "switch" into telerehabilitation procedures to ensure the safety of patients and operators but, concomitantly, the best rehabilitation level possible. Here, we planned a 5-month telespeech therapy programme, twice per week, of a patient with non-fluent aphasia following an intracerebral haemorrhage. Overall, treatment adherence based on the operator's assessments was high, and incomplete adherence for technical problems occurred very rarely. In line with the patient's feedback, acceptability was also positive, since he was constantly motivated during the sessions and the exercises performed autonomously, as confirmed by the speech therapist and caregiver, respectively. Moreover, despite the sequelae from the cerebrovascular event, evident in some writing tests due to the motor deficits in his right arm and the disadvantages typical of all telepractices, more relevant results were achieved during the telerehabilitation period compared to those of the "face-to-face" therapy before the COVID-19 outbreak. The telespeech therapy performed can be considered successful and the patient was able to return to work. Concluding, we support it as a feasible approach offering patients and their families the opportunity to continue the speech and language rehabilitation pathway, even at the time of pandemic

SARS-CoV-2 and the Nervous System: From Clinical Features to Molecular Mechanisms

Increasing evidence suggests that Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2) can also invade the central nervous system (CNS). However, findings available on its neurological manifestations and their pathogenic mechanisms have not yet been systematically addressed. A literature search on neurological complications reported in patients with COVID-19 until June 2020 produced a total of 23 studies. Overall, these papers report that patients may exhibit a wide range of neurological manifestations, including encephalopathy, encephalitis, seizures, cerebrovascular events, acute polyneuropathy, headache, hypogeusia, and hyposmia, as well as some non-specific symptoms. Whether these features can be an indirect and unspecific consequence of the pulmonary disease or a generalized inflammatory state on the CNS remains to be determined; also, they may rather reflect direct SARS-CoV-2-related neuronal damage. Hematogenous versus transsynaptic propagation, the role of the angiotensin II converting enzyme receptor-2, the spread across the blood-brain barrier, the impact of the hyperimmune response (the so-called &ldquo;cytokine storm&rdquo;), and the possibility of virus persistence within some CNS resident cells are still debated. The different levels and severity of neurotropism and neurovirulence in patients with COVID-19 might be explained by a combination of viral and host factors and by their interaction

Update on the Neurobiology of Vascular Cognitive Impairment: From Lab to Clinic

In the last years, there has been a significant growth in the literature exploring the pathophysiology of vascular cognitive impairment (VCI). As an &ldquo;umbrella term&rdquo; encompassing any degree of vascular-related cognitive decline, VCI is deemed to be the most common cognitive disorder in the elderly, with a significant impact on social and healthcare expenses. Interestingly, some of the molecular, biochemical, and electrophysiological abnormalities detected in VCI seem to correlate with disease process and progression, eventually promoting an adaptive plasticity in some patients and a maladaptive, dysfunctional response in others. However, the exact relationships between vascular lesion, cognition, and neuroplasticity are not completely understood. Recent findings point out also the possibility to identify a panel of markers able to predict cognitive deterioration in the so-called &ldquo;brain at risk&rdquo; for vascular or mixed dementia. This will be of pivotal importance when designing trials of disease-modifying drugs or non-pharmacological approaches, including non-invasive neuromodulatory techniques. Taken together, these advances could make VCI a potentially preventable cause of both vascular and degenerative dementia in late life. This review provides a timely update on the recent serological, cerebrospinal fluid, histopathological, imaging, and neurophysiological studies on this &ldquo;cutting-edge&rdquo; topic, including the limitations, future perspectives and translational implications in the diagnosis and management of VCI patients

Moderate Mocha Coffee Consumption Is Associated with Higher Cognitive and Mood Status in a Non-Demented Elderly Population with Subcortical Ischemic Vascular Disease

To date, interest in the role of coffee intake in the occurrence and course of age-related neurological and neuropsychiatric disorders has provided an inconclusive effect. Moreover, no study has evaluated mocha coffee consumption in subjects with mild vascular cognitive impairment and late-onset depression. We assessed the association between different quantities of mocha coffee intake over the last year and cognitive and mood performance in a homogeneous sample of 300 non-demented elderly Italian subjects with subcortical ischemic vascular disease. Mini Mental State Examination (MMSE), Stroop Colour-Word Interference Test (Stroop T), 17-items Hamilton Depression Rating Scalfe (HDRS), Activities of Daily Living (ADL), and Instrumental ADL were the outcome measures. MMSE, HDRS, and Stroop T were independently and significantly associated with coffee consumption, i.e., better scores with increasing intake. At the post-hoc analyses, it was found that the group with a moderate intake (two cups/day) had similar values compared to the heavy drinkers (≥three cups/day), with the exception of MMSE. Daily mocha coffee intake was associated with higher cognitive and mood status, with a significant dose-response association even with moderate consumption. This might have translational implications for the identification of modifiable factors for vascular dementia and geriatric depression

Moderate Mocha Coffee Consumption Is Associated with Higher Cognitive and Mood Status in a Non-Demented Elderly Population with Subcortical Ischemic Vascular Disease

To date, interest in the role of coffee intake in the occurrence and course of age-related neurological and neuropsychiatric disorders has provided an inconclusive effect. Moreover, no study has evaluated mocha coffee consumption in subjects with mild vascular cognitive impairment and late-onset depression. We assessed the association between different quantities of mocha coffee intake over the last year and cognitive and mood performance in a homogeneous sample of 300 non-demented elderly Italian subjects with subcortical ischemic vascular disease. Mini Mental State Examination (MMSE), Stroop Colour-Word Interference Test (Stroop T), 17-items Hamilton Depression Rating Scalfe (HDRS), Activities of Daily Living (ADL), and Instrumental ADL were the outcome measures. MMSE, HDRS, and Stroop T were independently and significantly associated with coffee consumption, i.e., better scores with increasing intake. At the post-hoc analyses, it was found that the group with a moderate intake (two cups/day) had similar values compared to the heavy drinkers (≥three cups/day), with the exception of MMSE. Daily mocha coffee intake was associated with higher cognitive and mood status, with a significant dose-response association even with moderate consumption. This might have translational implications for the identification of modifiable factors for vascular dementia and geriatric depression

Evaluation and Treatment of Vascular Cognitive Impairment by Transcranial Magnetic Stimulation

The exact relationship between cognitive functioning, cortical excitability, and synaptic plasticity in dementia is not completely understood. Vascular cognitive impairment (VCI) is deemed to be the most common cognitive disorder in the elderly since it encompasses any degree of vascular-based cognitive decline. In different cognitive disorders, including VCI, transcranial magnetic stimulation (TMS) can be exploited as a noninvasive tool able to evaluate in vivo the cortical excitability, the propension to undergo neural plastic phenomena, and the underlying transmission pathways. Overall, TMS in VCI revealed enhanced cortical excitability and synaptic plasticity that seem to correlate with the disease process and progression. In some patients, such plasticity may be considered as an adaptive response to disease progression, thus allowing the preservation of motor programming and execution. Recent findings also point out the possibility to employ TMS to predict cognitive deterioration in the so-called “brains at risk” for dementia, which may be those patients who benefit more of disease-modifying drugs and rehabilitative or neuromodulatory approaches, such as those based on repetitive TMS (rTMS). Finally, TMS can be exploited to select the responders to specific drugs in the attempt to maximize the response and to restore maladaptive plasticity. While no single TMS index owns enough specificity, a panel of TMS-derived measures can support VCI diagnosis and identify early markers of progression into dementia. This work reviews all TMS and rTMS studies on VCI. The aim is to evaluate how cortical excitability, plasticity, and connectivity interact in the pathophysiology of the impairment and to provide a translational perspective towards novel treatments of these patients. Current pitfalls and limitations of both studies and techniques are also discussed, together with possible solutions and future research agenda