RESUMO
BACKGROUND: The identification of biomarkers for the early diagnosis of Alzheimer's disease (AD) is a crucial goal of the current research. Blood biomarkers are less invasive, easier to obtain and achievable by a cheaper means than those on cerebrospinal fluid (CSF) and significantly more economic than functional neuroimaging investigations; thus, a great interest is focused on blood isoforms of the phosphorylated Tau protein (pTau), indicators of ongoing tau pathology (i.e. neurofibrillary tangles, NFTs, an AD neuropathological hallmark) in the central nervous system (CNS). However, current data often highlight discordant results about the ability of blood pTau to predict CSF status. OBJECTIVE: We aim to synthesise the studies that compared pTau levels on CSF and blood to assess their correlation in AD continuum. METHODS: We performed a narrative literature review using, first, MEDLINE (via PubMed) by means of MeSH terms, and then, we expanded the reults by means of Scopus and Web of Sciences to be as inclusive as possible. Finally, we added work following an expert opinion. Only papers presenting original data on pTau values on both blood and CSF were included. RESULTS: The 33 included studies show an extreme heterogeneity in terms of pTau isoform (pTau181, 217 and 231), laboratory methods, diagnostic criteria and choice of comparison groups. Most studies evaluated plasma pTau181, while data on other isoforms and serum are scarcer. DISCUSSION: Most papers identify a correlation between CSF and blood measurements. Furthermore, even when not specified, it is often possible to show an increase in blood pTau values as AD-related damage progresses in the AD continuum and higher values in AD than in other neurodegenerative diseases. Notably, plasma pTau231 seems the first biomarker to look for in the earliest and pre-clinical stages, quickly followed by pTau217 and, finally, by pTau181. CONCLUSIONS: Our results encourage the use of blood pTau for the early identification of patients with AD continuum.
Assuntos
Doença de Alzheimer , Biomarcadores , Proteínas tau , Humanos , Proteínas tau/líquido cefalorraquidiano , Proteínas tau/sangue , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Doença de Alzheimer/sangue , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico , FosforilaçãoRESUMO
Usually, positive neurological symptoms are considered as the consequence of a mere, afinalistic and abnormal increase in function of specific brain areas. However, according to the Theory of Active Inference, which argues that action and perception constitute a loop that updates expectations according to a Bayesian model, the brain is rather an explorer that formulates hypotheses and tests them to assess the correspondence between internal models and reality. Moreover, the cerebral cortex is characterised by a continuous "conflict" between different brain areas, which constantly attempt to expand in order to acquire more of the limited available computational resources, by means of their dopamine-induced neuroplasticity. Thus, it has recently been suggested that dreams, during rapid eye movement sleep (REMS), protect visual brain areas (deprived of their stimuli during rest) from being conquered by other normally stimulated ones. It is therefore conceivable that positive symptoms also have a functional importance for the brain. We evaluate supporting literature data of a 'defensive' role of positive symptoms and the relevance of dopamine-induced neuroplasticity in the context of neurodegenerative and psychiatric diseases. Furthermore, the possible functional significance of idiopathic REMS-related behavioural disorder as well as phantom limb syndrome is examined. We suggest that positive neurological symptoms are not merely a passive expression of a damage, but active efforts, related to dopamine-induced plasticity, to maintain a correct relationship between the external world and its brain representation, thus preventing healthy cortical areas from ousting injured ones.
Assuntos
Dopamina , Transtorno do Comportamento do Sono REM , Humanos , Teorema de Bayes , Encéfalo/fisiologia , Sono REM/fisiologiaRESUMO
Frontotemporal dementia (FTD) is a neurodegenerative disease of growing interest, since it accounts for up to 10% of middle-age-onset dementias and entails a social, economic, and emotional burden for the patients and caregivers. It is characterised by a (at least initially) selective degeneration of the frontal and/or temporal lobe, generally leading to behavioural alterations, speech disorders, and psychiatric symptoms. Despite the recent advances, given its extreme heterogeneity, an overview that can bring together all the data currently available is still lacking. Here, we aim to provide a state of the art on the pathogenesis of this disease, starting with established findings and integrating them with more recent ones. In particular, advances in the genetics field will be examined, assessing them in relation to both the clinical manifestations and histopathological findings, as well as considering the link with other diseases, such as amyotrophic lateral sclerosis (ALS). Furthermore, the current diagnostic criteria will be explored, including neuroimaging methods, nuclear medicine investigations, and biomarkers on biological fluids. Of note, the promising information provided by neurophysiological investigations, i.e., electroencephalography and non-invasive brain stimulation techniques, concerning the alterations in brain networks and neurotransmitter systems will be reviewed. Finally, current and experimental therapies will be considered.
Assuntos
Esclerose Lateral Amiotrófica , Demência Frontotemporal , Doenças Neurodegenerativas , Doença de Pick , Pessoa de Meia-Idade , Humanos , Demência Frontotemporal/diagnóstico , Demência Frontotemporal/terapia , Demência Frontotemporal/patologia , Esclerose Lateral Amiotrófica/patologia , Lobo Temporal/patologiaRESUMO
Mirror neurons show activity during both the execution (AE) and observation of actions (AO). The Mirror Neuron System (MNS) could be involved during motor imagery (MI) as well. Extensive research suggests that the cerebellum is interconnected with the MNS and may be critically involved in its activities. We gathered evidence on the cerebellum's role in MNS functions, both theoretically and experimentally. Evidence shows that the cerebellum plays a major role during AO and MI and that its lesions impair MNS functions likely because, by modulating the activity of cortical inhibitory interneurons with mirror properties, the cerebellum may contribute to visuomotor matching, which is fundamental for shaping mirror properties. Indeed, the cerebellum may strengthen sensory-motor patterns that minimise the discrepancy between predicted and actual outcome, both during AE and AO. Furthermore, through its connections with the hippocampus, the cerebellum might be involved in internal simulations of motor programs during MI. Finally, as cerebellar neuromodulation might improve its impact on MNS activity, we explored its potential neurophysiological and neurorehabilitation implications.
Assuntos
Cerebelo , Neurônios-Espelho , Neurônios-Espelho/fisiologia , Humanos , Cerebelo/fisiologia , Animais , Imaginação/fisiologia , Inibição Neural/fisiologia , Atividade Motora/fisiologiaRESUMO
Myasthenia gravis (MG) is the most common neuromuscular junction disorder. We evaluated the MG incidence rate in the province of Ferrara, Northern Italy, over two time frames (2008-2018 and 2019-2022, i.e., the COVID-19 pandemic) and considered early-onset (EOMG), late-onset (LOMG), and thymoma- and non-thymoma-associated MG. Moreover, in the second period, we assessed its possible relationship with SARS-CoV-2 infection or COVID-19 vaccination. We used a complete enumeration approach to estimate the MG incidence and its temporal trend. For the period of 2008-18, 106 new cases were identified (mean incidence rate 2.7/100,000 people). The highest rates were observed for the over-70 age group and in rural areas, with 17% of thymoma-associated MG. During the COVID-19 period, 29 new cases were identified (average incidence rate 2.1/100,000 people), showing a marked (though not statistically significant) decrease in the mean annual incidence compared to the previous period. Again, the highest rate was observed for the over-70 age group. The first period was in line with our previous observations for the period between 1985 and 2007, highlighting a rising incidence of LOMG and a marked decrease in EOMG. During the COVID-19 period, incidence rates were lower in the first years whereas, when the pandemic ended, the previous trend was confirmed.
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Cerebral venous thrombosis (CVT) is a rare cause of stroke, particularly in young adults. Several known thrombophilic conditions may lead to an increased CVT risk. Interestingly, few cases in the literature have reported an association between CVT and thyrotoxicosis. Here, we describe the case of a young woman with CVT and concomitant thyrotoxicosis, without any other known prothrombotic conditions. We also performed a literature review of CVT cases and hyperthyroidism, searching for all articles published in peer-reviewed journals. We identified 39 case reports/case series concerning patients with CVT associated with thyrotoxicosis, highlighting, in most cases, the association with additional known prothrombotic factors. We then discussed the possible mechanisms by which hyperthyroidism could underlie a pro-coagulative state resulting in CVT. Thyroid disease might be a more common prothrombotic risk factor than expected in determining CVT. However, in most cases, a coexistence of multiple risk factors was observed, suggesting a multifactorial genesis of the disorder. We hope that this work may alert clinicians to consider thyrotoxicosis as a potential risk factor for CVT, even in patients who apparently have no other pro-coagulative conditions.
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The Heidenhain Variant of Creutzfeldt-Jakob disease (CJD) is an uncommon early clinical syndrome of the otherwise regular sporadic CJD, which belongs to the group of prion diseases caused by a transmissible agent, the misfolded form of the prion protein. The most characteristic symptoms of CJD are rapidly progressive cognitive impairment, typical motor manifestations and mental and behavioural changes. Conversely, in the Heidenhain Variant, different kinds of visual disturbances are observed at onset due to microvacuolar spongiform degeneration or, less frequently, confluent spongiform changes in the parieto-occipital area, detectable through brain MRI with hyperintensity in T2-FLAIR or DWI in the same areas. Since this an extremely rare condition with a heterogeneous clinical presentation, it may easily be misdiagnosed with other diseases at the earlier stages. Here, we describe the case of a patient initially diagnosed with posterior reversible encephalopathy syndrome (PRES), presenting with visual disturbances and headache at onset in a context of poorly controlled arterial hypertension. Subsequently, a rapid worsening of cognitive decline, associated with myoclonus and startle reaction led to further investigations, shifting the diagnosis toward a rapidly evolving neurodegenerative form. This hypothesis was also supported by EEG traces, MRI and CSF analysis. Finally, the clinical-instrumental evolution confirmed the diagnosis of Heidenhain Variant of CJD.