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 "cytokine storm"), 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.
In the last years, there has been a significant growth in the literature exploring the pathophysiology of vascular cognitive impairment (VCI). As an "umbrella term" 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 "brain at risk" 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 "cutting-edge" topic, including the limitations, future perspectives and translational implications in the diagnosis and management of VCI patients.
Acute brain ischemia causes changes in several neural networks and related cortico-subcortical excitability, both in the affected area and in the apparently spared contralateral hemisphere. The ...modulation of these processes through modern techniques of noninvasive brain stimulation, namely repetitive transcranial magnetic stimulation (rTMS), has been proposed as a viable intervention that could promote post-stroke clinical recovery and functional independence. This review provides a comprehensive summary of the current evidence from the literature on the efficacy of rTMS applied to different clinical and rehabilitative aspects of stroke patients. A total of 32 meta-analyses published until July 2019 were selected, focusing on the effects on motor function, manual dexterity, walking and balance, spasticity, dysphagia, aphasia, unilateral neglect, depression, and cognitive function after a stroke. Only conventional rTMS protocols were considered in this review, and meta-analyses focusing on theta burst stimulation only were excluded. Overall, both HF-rTMS and LF-rTMS have been shown to be safe and well-tolerated. In addition, the current literature converges on the positive effect of rTMS in the rehabilitation of all clinical manifestations of stroke, except for spasticity and cognitive impairment, where definitive evidence of efficacy cannot be drawn. However, routine use of a specific paradigm of stimulation cannot be recommended yet due to a significant level of heterogeneity of the studies in terms of protocols to be set and outcome measures that have to be used. Future studies need to preliminarily evaluate the most promising protocols before going on to multicenter studies with large cohorts of patients in order to achieve a definitive translation into daily clinical practice.
Sex differences in vascular cognitive impairment (VCI) at risk for future dementia are still debatable. Transcranial magnetic stimulation (TMS) is used to evaluate cortical excitability and the ...underlying transmission pathways, although a direct comparison between males and females with mild VCI is lacking.
Sixty patients (33 females) underwent clinical, psychopathological, functional, and TMS assessment. Measures of interest consisted of: resting motor threshold, latency of motor evoked potentials (MEPs), contralateral silent period, amplitude ratio, central motor conduction time (CMCT), including the F wave technique (CMCT-F), short-interval intracortical inhibition (SICI), intracortical facilitation, and short-latency afferent inhibition, at different interstimulus intervals (ISIs).
Males and females were comparable for age, education, vascular burden, and neuropsychiatric symptoms. Males scored worse at global cognitive tests, executive functioning, and independence scales. MEP latency was significantly longer in males, from both sides, as well CMCT and CMCT-F from the left hemisphere; a lower SICI at ISI of 3 ms from the right hemisphere was also found. After correction for demographic and anthropometric features, the effect of sex remained statistically significant for MEP latency, bilaterally, and for CMCT-F and SICI. The presence of diabetes, MEP latency bilaterally, and both CMCT and CMCT-F from the right hemisphere inversely correlated with executive functioning, whereas TMS did not correlate with vascular burden.
We confirm the worse cognitive profile and functional status of males with mild VCI compared to females and first highlight sex-specific changes in intracortical and cortico-spinal excitability to multimodal TMS in this population. This points to some TMS measures as potential markers of cognitive impairment, as well as targets for new drugs and neuromodulation therapies.
Although cerebral white matter lesions (WMLs) are considered as a risk factor for vascular dementia, data on their impact on cerebral hemodynamics are scarce. We test and compare transcranial Doppler ...(TCD) features in WML patients with or without associated cognitive impairment.
A sample of non-demented elderly patients with WMLs was consecutively recruited. Mean blood flow velocity (MBFV), pulsatility index (PI), peak systolic blood flow velocity (PSV), end-diastolic blood flow velocity (EDV), and resistivity index (RI) were recorded from the middle cerebral artery bilaterally. Global cognitive functioning, frontal lobe abilities, functional status, and WML severity were also assessed.
161 patients satisfying the clinical criteria for vascular cognitive impairment-no dementia (VCI-ND) were age-matched with 97 presenting WMLs without any cognitive deficit. VCI-ND patients exhibited a decrease in MBFV and EDV, as well as an increase in PI, RI, and PSV. Moreover, a significant correlation between all TCD parameters and the severity of executive dysfunction was observed, whereas PI, RI, and EDV were significantly correlated with the WML load.
VCI-ND showed a hemodynamic pattern indicative of cerebral hypoperfusion and enhanced vascular resistance. These changes may be considered as the TCD correlate of VCI-ND due to microcirculation pathology. TCD provides useful indices of the occurrence and severity of small vessel disease and executive dysfunction in elderly patients at risk of future dementia.
•This review presents the contribution of TMS to the management of dementia.•TMS can be used as a biomarker of the excitability and function of cerebral cortex in dementia.•Increasing evidence ...supports the beneficial effects of rTMS in Alzheimer’s disease-related dementias at mild/early stage.
Transcranial magnetic stimulation (TMS) is a powerful tool to probe in vivo brain circuits, as it allows to assess several cortical properties such asexcitability, plasticity and connectivity in humans. In the last 20 years, TMS has been applied to patients with dementia, enabling the identification of potential markers of thepathophysiology and predictors of cognitive decline; moreover, applied repetitively, TMS holds promise as a potential therapeutic intervention.
The objective of this paper is to present a comprehensive review of studies that have employed TMS in dementia and to discuss potential clinical applications, from the diagnosis to the treatment.
To provide a technical and theoretical framework, we first present an overview of the basic physiological mechanisms of the application of TMS to assess cortical excitability, excitation and inhibition balance, mechanisms of plasticity and cortico-cortical connectivity in the human brain. We then review the insights gained by TMS techniques into the pathophysiology and predictors of progression and response to treatment in dementias, including Alzheimer’s disease (AD)-related dementias and secondary dementias. We show that while a single TMS measure offers low specificity, the use of a panel of measures and/or neurophysiological index can support the clinical diagnosis and predict progression.
In the last part of the article, we discuss the therapeutic uses of TMS. So far, only repetitive TMS (rTMS) over the left dorsolateral prefrontal cortex and multisite rTMS associated with cognitive training have been shown to be, respectively, possibly (Level C of evidence) and probably (Level B of evidence) effective to improve cognition, apathy, memory, and language in AD patients, especially at a mild/early stage of the disease. The clinical use of this type of treatment warrants the combination of brain imaging techniques and/or electrophysiological tools to elucidate neurobiological effects of neurostimulation and to optimally tailor rTMS treatment protocols in individual patients or specific patient subgroups with dementia or mild cognitive impairment.
Summary Altered responses to transcranial magnetic stimulation (TMS) in obstructive sleep apnea syndrome (OSAS), restless legs syndrome (RLS), insomnia, and sleep-deprived healthy subjects have been ...reported. We have reviewed the relevant literature in order to identify eventual distinctive electrocortical profiles based on single and paired-pulse TMS, sensorimotor modulation, plasticity-related and repetitive TMS measures. Although obtained from heterogeneous studies, the detected changes might be the result of the different pathophysiological substrates underlying OSAS, RLS, insomnia and sleep deprivation rather than reflect the general effect of non-specific sleep loss and instability. OSAS tends to exhibit an increased motor cortex inhibition, which is reduced in RLS; intracortical excitability seems to be in favor of an “activating” profile in chronic insomnia and in sleep-deprived healthy individuals. Abnormal plasticity-related TMS phenomena have been demonstrated in OSAS and RLS. This review provides a perspective of TMS techniques by further understanding the role of neurotransmission pathways and plastic remodeling of neuronal networks involved in common sleep disorders. TMS might be considered a valuable tool in the assessment of sleep disorders, the evaluation of the effect of therapy and the design of non-pharmacological approaches.
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