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The neurological impact of COVID-19 is a rising concern among medical professionals, as patients continue to experience symptoms long after their recovery. This condition, known as neurological post-acute sequelae of COVID-19 (Neuro-PASC), can last for more than 12 weeks and includes symptoms such as attention disorders, brain fog, fatigue, and memory loss. However, researchers and health professionals face significant challenges in understanding how COVID-19 affects the brain, limiting the development of effective prevention and treatment strategies. In this mini-review, we provide readers with up-to-date information on the imaging techniques currently available for measuring the neurological impact of post-SARS-CoV-2 infection. Our search of PubMed and Google Scholar databases yielded 38 articles on various brain imaging techniques, including structural MRI (magnetic resonance imaging), functional MRI, diffusion MRI, susceptibility-weighted imaging, SPECT (single-photon emission computed tomography) imaging, and PET (positron emission tomography) imaging. We also discuss the optimal usage, limitations, and potential benefits of these techniques. Our findings show that various cerebral imaging techniques have been evaluated to identify a reliable marker for Neuro-PASC. For instance, 18F-FDG-PET/CT and functional MRI have demonstrated hypometabolism in cerebral regions that are directly linked to patient symptoms. Structural MRI studies have revealed different findings, such as infarcts, white matter atrophy, and changes in gray matter volumes. One SPECT imaging study noted frontal lobe hypometabolism, while diffusion MRI showed increased diffusivity in the limbic and olfactory cortical systems. The sequence SWI showed abnormalities primarily in white matter near the gray-white matter junction. A study on 18F-amyloid PET/CT found amyloid lesions in frontal and anterior cingulate cortex areas, and a study on arterial spin labeling (ASL) found hypoperfusion primarily in the frontal lobe. While accessibility and cost limit the widespread use of 18F-FDG-PET/CT scans and functional MRI, they seem to be the most promising techniques. SPECT, SWI sequence, and 18F-amyloid PET/CT require further investigation. Nevertheless, imaging remains a reliable tool for diagnosing Neuro-PASC and monitoring recovery.
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Introduction: As the repercussions from the COVID-19 pandemic continue to unfold, an ever-expanding body of evidence suggests that infection also elicits pathophysiological manifestations within the central nervous system (CNS), known as neurological symptoms of post-acute sequelae of COVID infection (NeuroPASC). Although the neurological impairments and repercussions associated with NeuroPASC have been well described in the literature, its etiology remains to be fully characterized. Objectives: This mini-review explores the current literature that elucidates various mechanisms underlining NeuroPASC, its players, and regulators, leading to persistent neuroinflammation of affected individuals. Specifically, we provide some insights into the various roles played by microglial and astroglial cell reactivity in NeuroPASC and how these cell subsets potentially contribute to neurological impairment in response to the direct or indirect mechanisms of CNS injury. Discussion: A better understanding of the mechanisms and biomarkers associated with this maladaptive neuroimmune response will thus provide better diagnostic strategies for NeuroPASC and reveal new potential mechanisms for therapeutic intervention. Altogether, the elucidation of NeuroPASC pathogenesis will improve patient outcomes and mitigate the socioeconomic burden of this syndrome.
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Long COVID syndrome, also known as post-acute sequelae of COVID-19 (PASC), is characterized by persistent symptoms lasting 3-12 weeks post SARS-CoV-2 infection. Patients suffering from PASC can display a myriad of symptoms that greatly diminish quality of life, the most frequent being neuropsychiatric. Thus, there is an eminent need to diagnose and treat PASC related neuropsychiatric manifestation (neuro-PASC). Evidence suggests that liquid biomarkers could potentially be used in the diagnosis and monitoring of patients. Undoubtedly, such biomarkers would greatly benefit clinicians in the management of patients; however, it remains unclear if these can be reliably used in this context. In this mini review, we highlight promising liquid (blood and cerebrospinal fluid) biomarkers, namely, neuronal injury biomarkers NfL, GFAP, and tau proteins as well as neuroinflammatory biomarkers IL-6, IL-10, TNF-α, and CPR associated with neuro-PASC and discuss their limitations in clinical applicability.
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Background and objectives: An increasing number of research studies point toward the importance and prevalence of long-term neurocognitive symptoms following infection with COVID-19. Our objectives were to capture the prevalence of cognitive impairments from 1 to 16 months post-COVID-19 infection, assess the changes in neuropsychological functions over time, and identify factors that can predict long-term deficits in cognition. Methodology: A cross-sectional research design was adopted to compare four sub-samples recruited over a 16-month timeframe (1-4, 5-8, 9-12, and 13-16 months). Phone interviews were conducted at least 6 weeks after being infected by COVID-19. Sociodemographic and clinical questionnaires were administered followed by standardized neurocognitive and psychological tests and health questionnaires screening cognitive symptoms, anxiety, depression, fatigue, and autonomy. Results: Regarding general health questionnaires, 55.2% of the 134 participants had symptoms of psychiatric illness, while 21.6% of patients had moderate-to-severe anxiety or depression. Cognitive efficiency was diminished in 19.4% of our population. Executive dysfunction was screened in 56% of patients, and an impairment of cognitive flexibility and inhibition was revealed in 38.8%. Depression, hospital or intensive care unit (ICU) admission, and the duration of hospital or ICU stay were associated with an inhibition deficit. The duration elapsed from the initial infection, and the neurocognitive assessment was not associated with a decrease in inhibition deficit. The prevalence of cognitive impairments, other than inhibition deficit, tended to decrease during the study period. Discussion: This study supports the extensive literature on the cognitive and neuropsychiatric sequelae of COVID-19 and highlights long-lasting inhibition deficits, while other cognitive functions seemed to improve over time. The severity of infection could interact as a catalyst in the complex interplay between depression and executive functions. The absence of a relation between inhibition deficits and sociodemographic or medical factors reinforces the need for cognitive screening in all COVID-19 patients. Future research should focus on inhibition deficits longitudinally to assess the progression of this impairment.
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Spinocerebellar ataxia type 31 (SCA31) is an autosomal dominant disease, classified amongst pure cerebellar ataxias (ADCA type 3). While SCA31 is the third most prevalent autosomal dominant ataxia in Japan, it is extremely rare in other countries. A literature review was conducted on PubMed, where we included all case reports and studies describing the clinical presentation of original SCA31 cases. The clinical and radiological features of 374 patients issued from 25 studies were collected. This review revealed that the average age of onset was 59.1 ± 3.3 years, with symptoms of slowly progressing ataxia and dysarthria. Other common clinical features were oculomotor dysfunction (38.8%), dysphagia (22.1%), hypoacousia (23.3%), vibratory hypoesthesia (24.3%), and dysreflexia (41.6%). Unfrequently, abnormal movements (7.4%), extrapyramidal symptoms (4.5%) and cognitive impairment (6.9%) may be observed. Upon radiological examination, clinicians can expect a high prevalence of cerebellar atrophy (78.7%), occasionally accompanied by brainstem (9.1%) and cortical (9.1%) atrophy. Although SCA31 is described as a slowly progressive pure cerebellar syndrome characterized by cerebellar signs such as ataxia, dysarthria and oculomotor dysfunction, this study evaluated a high prevalence of extracerebellar manifestations. Extracerebellar signs were observed in 52.5% of patients, primarily consisting of dysreflexia, vibratory hypoesthesia and hypoacousia. Nonetheless, we must consider the old age and longstanding disease course of patients as a confounding factor for extracerebellar sign development, as some may not be directly attributable to SCA31. Clinicians should consider SCA31 in patients with a hereditary, pure cerebellar syndrome and in patients with extracerebellar signs.
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Ataxia Cerebelosa , Ataxias Espinocerebelosas , Humanos , Persona de Mediana Edad , Disartria/complicaciones , Hipoestesia , Ataxias Espinocerebelosas/complicaciones , Ataxias Espinocerebelosas/diagnóstico por imagen , Ataxias Espinocerebelosas/genética , Ataxia Cerebelosa/complicaciones , Atrofia/complicacionesRESUMEN
INTRODUCTION: Physical exercise and cognitive training have the potential to enhance cognitive function and mobility in older adults at risk of Alzheimer's disease and related dementia (ADRD), but little is known about the feasibility of delivering multidomain interventions in home settings of older adults at risk of ADRD. This study aims to assess the feasibility of home-based delivery of exercise and cognitive interventions, and to evaluate the relationship between participants' intervention preferences and their subsequent adherence. Secondary objectives include the effect of the interventions on ADRD risk factors, including frailty, mobility, sleep, diet and psychological health. METHODS AND ANALYSIS: The SYNchronising Exercises, Remedies in GaIt and Cognition at Home (SYNERGIC@Home) feasibility trial is a randomised control trial that follows a 2×2 factorial design, with a 16-week home-based intervention programme (3 sessions per week) of physical exercises and cognitive training. Participants will be randomised in blocks of four to one of the following four arms: (1) combined exercise (aerobic and resistance)+cognitive training (NEUROPEAK); (2) combined exercise+control cognitive training (web searching); (3) control exercise (balance and toning)+cognitive training; and (4) control exercise+control cognitive training. SYNERGIC@Home will be implemented through video conferencing. Baseline and post-intervention assessments at 4-month and 10-month follow-up will include measures of cognition, frailty, mobility, sleep, diet and psychological health. Primary feasibility outcome is adherence to the interventions. Primary analytic outcome is the relationship between pre-allocation preference for a given intervention and subsequent adherence to the allocated intervention. A series of secondary analytic outcomes examining the potential effect of the individual and combined interventions on cognitive, mobility and general well-being will be measured at baseline and follow-up. ETHICS AND DISSEMINATION: Ethics approval was granted by the relevant research ethics boards. Findings of the study will be presented to stakeholders and published in peer-reviewed journals and at provincial, national and international conferences. TRIAL REGISTRATION NUMBER: NCT04997681, Pre-results.
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Enfermedad de Alzheimer , Cognición , Anciano , Método Doble Ciego , Ejercicio Físico , Estudios de Factibilidad , Marcha , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
We present a rare case of meningoradiculitis occurring after mRNA COVID-19 vaccination. This patient, with a history of inflammatory arthritis following rubella vaccination, presented to the emergency department 4 days after her vaccination with both central and radicular nervous system symptoms. Symptoms included pain, sensory and motor deficits in L5 roots distribution, along with signs of central irritation, such as headache, difficulty concentrating and a Babinski sign. MRI showed bilateral L5 nerve roots enhancement. Lumbar puncture showed elevated protein and IgG, and relevant serologies excluded common causes. Prednisone and physical therapy helped the patient to achieve near complete recovery nine weeks after presentation. We concluded that this patient presented meningoradiculitis probably secondary to her vaccination in a context of possible overactive immune system. While such presentations might be rare, and do not constitute a general reason to abstain from vaccination, they must be well recognized and treated.
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Multiple Sclerosis (MS) is a neurodegenerative disease associated with cognition and balance impairments, which can lead to accidental falls. Postural control requires cognitive resources. This interaction is quantifiable by using the dual-task paradigm. The cognitive-postural interference (CPI) is commonly evaluated through an assessment of the dual-task cost (DTC). The aim of this review was to summarize literature related to process, results and effects of CPI in MS patients. The Prisma statement was used to guide this systematic review. Eligible articles had to include participants with MS for whom CPI was assessed using the DTC. A total of 14 articles meeting inclusion criteria were retained. All studies used the double stance with eyes open for the postural task component. Three types of cognitive tasks were used: Stroop Color-Word Test (SCWT), Word List Generation and Backward Counting. However, cognitive task scores in single or dual task were unavailable in 11 studies, which prevented calculating the DTC for that task. Prioritization instructions were provided in seven studies. Mutual interference was shown in three studies, postural interference in nine and postural facilitation in two. This review highlights the presence of CPI among MS patients. Postural interference usually occurred during dual task while cognitive performance during dual task was rarely reported. Postural task performance does not appear to vary based on EDSS level. We advise authors of future studies to use the SCWT in combination with postural task measure (sway area and postural sway) for DT assessment, with explicit prioritization instructions. Further, the cognitive and postural tasks should be performed in ST and DT and all results should be presented.
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BACKGROUND: Skin biopsy is the most relevant tool to diagnose small-fiber neuropathy. A well-documented normal dataset for intraepidermal nerve fiber in the distal leg is required to improve its diagnostic value. METHODS: Three hundred healthy subjects were enrolled in the study, after clinical and biological screening to exclude neurological and systemic pathologies. A distal leg biopsy was taken and intraepidermal nerve fiber density after protein gene product-9.5 immunocytochemistry with brightfield microscopy was determined. Morphological variations of intraepidermal nerve fibers, previously described in small-fiber neuropathies, were analyzed. One hundred biopsies were also analyzed at the ultrastructural level. FINDINGS: The median number of fibers was lower in men compared to women and decreased with age. Using statistical modeling taking into account age and gender, we calculated the 5th percentile of intraepidermal nerve fiber density as follows: 7.6156-0.0769 x age (years) + 1.5506 x gender (woman = 1; man = 0). We observed a low frequency of large swellings or horizontal branchings but an increasing frequency of small swellings of intraepidermal nerve fibers and irregular distribution along the dermal-epidermal junction with age. Axonal diameter of unmyelinated fibers of the papillary dermis did not vary with age or gender. Ultrastructural analysis also showed that fiber endings in close apposition to Merkel cells should not be mistaken for small-fiber swellings. CONCLUSIONS: Our dataset allows accurate calculation of the normal density of intraepidermal nerve fibers for each year of age and provides original morphological observations that improve the diagnostic value of skin biopsy in the distal leg for small-fiber neuropathy.