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Central and peripheral nervous system involvement by COVID-19: a systematic review of the pathophysiology, clinical manifestations, neuropathology, neuroimaging, electrophysiology, and cerebrospinal fluid findings
Juan I. Guerrero ORCID: orcid.org/0000-0001-8750-65541,
Luis A. Barragán ORCID: orcid.org/0000-0003-3197-56711,
Juan D. Martínez ORCID: orcid.org/0000-0002-3042-76331,
Juan P. Montoya ORCID: orcid.org/0000-0001-9722-45501,
Alejandra Peña ORCID: orcid.org/0000-0002-3679-94111,
Fidel E. Sobrino ORCID: orcid.org/0000-0001-8334-62152,3,
Zulma Tovar-Spinoza ORCID: orcid.org/0000-0002-5275-75024 &
Kemel A. Ghotme ORCID: orcid.org/0000-0001-6802-43731,5
SARS-CoV-2 can affect the human brain and other neurological structures. An increasing number of publications report neurological manifestations in patients with COVID-19. However, no studies have comprehensively reviewed the clinical and paraclinical characteristics of the central and peripheral nervous system's involvement in these patients. This study aimed to describe the features of the central and peripheral nervous system involvement by COVID-19 in terms of pathophysiology, clinical manifestations, neuropathology, neuroimaging, electrophysiology, and cerebrospinal fluid findings.
We conducted a comprehensive systematic review of all the original studies reporting patients with neurological involvement by COVID-19, from December 2019 to June 2020, without language restriction. We excluded studies with animal subjects, studies not related to the nervous system, and opinion articles. Data analysis combined descriptive measures, frequency measures, central tendency measures, and dispersion measures for all studies reporting neurological conditions and abnormal ancillary tests in patients with confirmed COVID-19.
A total of 143 observational and descriptive studies reported central and peripheral nervous system involvement by COVID-19 in 10,723 patients. Fifty-one studies described pathophysiologic mechanisms of neurological involvement by COVID-19, 119 focused on clinical manifestations, 4 described neuropathology findings, 62 described neuroimaging findings, 28 electrophysiology findings, and 60 studies reported cerebrospinal fluid results. The reviewed studies reflect a significant prevalence of the nervous system's involvement in patients with COVID-19, ranging from 22.5 to 36.4% among different studies, without mortality rates explicitly associated with neurological involvement by SARS-CoV-2. We thoroughly describe the clinical and paraclinical characteristics of neurological involvement in these patients.
Our evidence synthesis led to a categorical analysis of the central and peripheral neurological involvement by COVID-19 and provided a comprehensive explanation of the reported pathophysiological mechanisms by which SARS-CoV-2 infection may cause neurological impairment. International collaborative efforts and exhaustive neurological registries will enhance the translational knowledge of COVID-19's central and peripheral neurological involvement and generate therapeutic decision-making strategies.
This review was registered in PROSPERO 2020 CRD42020193140 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020193140
In 2020, infections by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affected more than 83 million people around the world, and coronavirus disease 2019 (COVID-19) caused more than 1.8 million deaths [1], leading to one of the most devastating pandemics declared by the World Health Organization in the twenty-first Century [2]. SARS-CoV-2 is a 29,903 bp single-stranded RNA encapsulated virus from the Coronaviridae family, betacoronavirus subfamily, capable of affecting the human brain and other structures of the nervous system [2,3,4].
An increasing number of publications report abnormalities of central and peripheral nervous systems in patients with severe and non-severe COVID-19 [5,6,7,8]. Several studies have reported neurological manifestations of COVID-19 and different abnormal findings in ancillary tests. However, no studies in the first months of pandemics have comprehensively reviewed the clinical and paraclinical characteristics of the involvement of the central nervous system (CNS) and peripheral nervous system (PNS) in patients affected by this infectious disease.
The purpose of this systematic review is to describe the characteristics of the central and peripheral nervous system involvement by COVID-19 in terms of pathophysiology, clinical manifestations, neuropathology, neuroimaging, electrophysiology, and cerebrospinal fluid (CSF) findings. This study's results may help clinicians and researchers approach patients with this condition and generate new inquiries with implications for practice. The explicit questions addressed were: What are the characteristics of the central and peripheral nervous system involvement by COVID-19? What is the described pathophysiology of central and peripheral nervous system involvement by COVID-19? What are the clinical manifestations, neuropathology, neuroimaging, electrophysiology, and cerebrospinal fluid findings in patients with central and peripheral nervous system involvement by COVID-19?
We conducted a comprehensive systematic review of all the original studies reporting patients with neurological involvement by COVID-19. We followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement [9, 10]. This review was registered in PROSPERO (CRD42020193140) on July 24, 2020.
We included all original studies, including cohort, case-control, time series, case series, case reports, and letters to the editor containing a complete description of human subjects with confirmed SARS-CoV-2 infection and CNS or PNS involvement. We set the timeframe between December 2019 and June 2020 without language restriction. We excluded studies with animal subjects, studies not related to the nervous system involvement of SARS-CoV-2, publications about coronaviruses other than SARS CoV-2, reports of individuals with suspected or not confirmed infection by SARS-CoV-2, and opinion articles.
We conducted a systematic search in PubMed/MEDLINE, Scopus, Cochrane Library, LILACS, and SciELO databases from June 4 to June 30, 2020, using the MeSH terms: ("COVID-19" OR "Coronavirus" OR "Severe Acute Respiratory Syndrome Coronavirus 2") AND ("Central Nervous System" OR "Peripheral Nervous System"). We added additional terms for amplifying the scope of the review, namely: "CSF", "Cerebrospinal Fluid", "Brain AND Spine Imaging", "Neuropathology", "Peripheral Neuropathy", and "Seizures" and sought for individual patient-level data and summary estimates.
Five reviewers simultaneously screened titles, abstracts, and keywords to check for the fulfillment of inclusion and exclusion criteria. The authors reviewed the resulting articles independently in full text and hand-searched each article's reference lists to ensure literature saturation. From the resulting studies, we extracted the name of first author, title, year of publication, journal, country, study design, peripheral or central nervous system involvement, and discussed topics (physiopathology, clinical manifestations, neuropathology, neuroradiology, electrophysiology studies, or cerebrospinal fluid findings). We performed a quality assessment at the study level. For case reports and case series, we applied the CARE checklist. Since most of the studies were observational or descriptive, internal validity aspects such as randomization, treatment allocation, or blinding were not applicable. We assessed external validity and generalizability aspects. All reviewers participated in the quality assessment and resolved disagreements by consensus. The data extracted were processed in Excel spreadsheets and categorized into pathophysiology, clinical features, neuropathology, neuroimaging, electrophysiology, and CSF abnormalities.
Evidence synthesis and data analysis
We performed an evidence synthesis taking into account all selected studies, using a deductive method. Three senior reviewers checked the received data from the selected studies. All authors made decisions and resolved disagreements between individual judgments by consensus. Data analysis combined descriptive measures, frequency measures, central tendency measures, and dispersion measures for all studies reporting neurological conditions and abnormal ancillary tests in patients with confirmed COVID-19.
This review yielded 143 original publications reporting CNS and PNS involvement by COVID-19, with the selected characteristics alone or combined (Fig. 1).
Study selection
The included studies were essentially observational and descriptive. From the total, 119 focus on clinical manifestations, 62 describe neuroimaging findings, 60 studies report cerebrospinal fluid results, 51 describe pathophysiologic mechanisms of CNS and PNS involvement by COVID-19, 28 report electrophysiology findings, and four describe neuropathology findings. Among all studies reviewed, we found a total of 10,723 patients with a confirmed diagnosis of COVID-19 who displayed features compatible with neurological involvement. Among them, we found 1633 patients with specific nosological entities or clinical conditions affecting the central nervous system and 43 the peripheral nervous system (Table 1). The remaining 9047 patients reportedly presented with one or more neurological signs and symptoms not attributed to a specific clinical condition or nosological entity. Neurological manifestations of COVID-19 were more common in the inpatient than the outpatient setting (58.5% versus 41.5%, respectively). Indeed, neurological involvement in a patient with confirmed SARS-CoV-2 infection increased the probability of being hospitalized by approximately 81% [11].
Table 1 Neurological conditions associated with COVID-19
From the total, 8885 (86,3%) reports of neurological signs and symptoms were related to CNS, while 1414 (13,7%) were related to PNS. Figure 2 summarizes the main neurological manifestations of patients with COVID-19 and CNS or PNS compromise.
Summary of central and peripheral nervous system involvement by SARS CoV-2. Figure created by the authors using Microsoft PowerPoint partly based on public domain images via Wikimedia Commons. SARS-CoV-2 virus adapted from CDC/ Alissa Eckert, MS; Dan Higgins, MAM, Public domain, via Wikimedia Commons. Nervous system diagram adapted from Medium69, Jmarchn, CC BY-SA 4.0 <https://creativecommons.org/licenses/by-sa/4.0>, via Wikimedia Commons. CNS: Central nervous system; PNS: peripheral nervous system
Tables 2 and 3 specifically describe the signs and symptoms indicating central and peripheral nervous system involvement, respectively.
Table 2 Distribution of signs and symptoms indicating central nervous system involvement in patients with COVID-19
Table 3 Distribution of signs and symptoms indicating peripheral nervous system involvement in patients with COVID-19
Figure 3 summarizes the main neuroimaging findings associated with COVID-19, while Table 4 represents the main CSF findings. Most of the included studies did not report mortality rates explicitly associated with neurological involvement by SARS-CoV-2.
Neuroimaging findings and association with clinical conditions in patients with COVID-19. Figure created by the authors using SmartDraw. CSF: cerebrospinal fluid
Table 4 Cerebrospinal fluid (CSF) findings in patients with COVID-19 and different neurological conditions
The reviewed studies reflect a significant prevalence of the nervous system's involvement in patients with COVID-19. Neurological manifestations appear in a range of 22.5 to 36.4% of all COVID-19 patients among different studies [6, 11,12,13,14]. We classified them in diffuse and focal CNS signs and symptoms, seizures, cranial nerve impairment, encephalopathy, neuroinflammatory disorders, acute cerebrovascular disease, and peripheral neuropathies.
Diffuse CNS signs and symptoms
Fifty-three studies reported 8129 diffuse signs and symptoms of CNS involvement by COVID-19 (Table 2), including neuropsychiatric disorders (61.3%), headache (22.2%), dizziness (6.6%), consciousness impairment (5.2%), delirium (4.3%) nausea/vomiting (0.3%), and nuchal rigidity (0.1%). Psychiatric symptoms included anxiety, mood disorders, psychosis, insomnia, and others. These symptoms are described in depth in other studies [11, 15, 16] and are not the focus of this review. Headache is, indeed, one of the most common neurological manifestations of SARS-CoV-2 infection, with a variability range of 8 to 39% of cases [13, 17]. Headache can be a primary process in these patients or part of a broad spectrum of neurological syndromes such as meningitis, encephalitis, vasculitis, elevated intracranial pressure, and other clinical conditions associated with COVID-19's neuroinflammatory mechanisms and other underlying systemic causes [7]. Impairment of consciousness and arousal is another common neurological disturbance, documented in up to 37% of patients with COVID-19 as a manifestation of encephalopathy [6, 7]. Delirium was present in 20 to 65% of patients with SARS-CoV-2 infection [18]. It can be attributed directly to SARS-CoV-2 invasive mechanisms to the CNS, leading to a neuroinflammatory response or a multifactorial compromise secondary to sedative therapies, mechanical ventilation, and environmental factors, including social isolation [15]. On the other hand, delirium in critically ill patients with COVID-19 may be a prodromal symptom of infection and hypoxia secondary to severe respiratory failure [15] or an isolated manifestation of COVID-19 [19]. Delirium can also overlap an underlying cognitive impairment, which generates a baseline vulnerability state. However, the elevation of inflammatory markers indicates a concomitant immune response as a precipitant [18]. Furthermore, a history of delirium can increase the risk of post-intensive care syndrome, including cognitive impairment, mental state disorders (such as depression, anxiety, and post-traumatic stress disorder), and physical impairment after leaving the intensive care unit [15]. Dizziness is also a prevalent neurological manifestation, ranging between 7 and 9.4% of patients admitted to intensive care units [20] and 26.21% in general series [6, 17]. Nausea and vomiting are also common neurologic manifestations, with an estimated prevalence of 5% [4]. Their presence may be related to an impairment in the CNS structures related to emesis control in the dorsal vagal complex in the medulla oblongata caused by SARS-CoV-2 [21].
Focal CNS signs and symptoms
Twenty-eight studies reported 410 patients with focal neurological disturbances (Table 2), including corticospinal and corticobulbar tract impairment, ataxia, dysarthria, amnesia, aphasia, retrochiasmatic visual field alterations, and extrapyramidal disorders. Most of these disturbances were associated with stroke in patients with COVID-19 and are discussed below in this article.
Twenty-eight studies reported seizures in 346 patients with COVID-19. When specified, around 90% of them were new-onset seizures, and 10% occurred in patients with a previous history of controlled epilepsy [22,23,24,25]. Most reports did not specify the seizure type in 324 patients, while a few studies documented generalized or focal seizures [24, 26,27,28,29,30,31,32,33], focal or diffuse non-convulsive status epilepticus [34], seizure-like motor events [24], and non-epileptic convulsive syncope [25] (Table 2). Although COVID-19 patients may present seizures due to hypoxia, metabolic derangements, organ failure, or cerebral damage [35], SARS-CoV-2 systemic infection per se represents a minimal risk for seizures during acute illness [36]. In a retrospective multicentric study aiming to evaluate the incidence and risk of acute symptomatic seizures in 304 patients without a prior history of epilepsy, there were no new-onset seizures or status epilepticus during the COVID-19 acute phase [36]. The association between seizures and the severity of COVID-19 remains a matter of debate with evidence in favor [26] and against [22]. There was a previous history of cognitive impairment, older age, and higher levels of creatine-kinase and C-reactive protein after admission for COVID-19 [35] for many patients with seizures. For patients with baseline epilepsy, SARS-CoV-2 infection may trigger seizures; therefore, it is ideal to anticipate breakthrough seizures and prescribe short-term antiseizure medications opportunely [7]. Continuous electroencephalography (EEG) monitoring in any patient with a critical medical condition who has changed in mental status facilitates the timely diagnosis of non-convulsive status epilepticus [14].
Cranial nerve impairment
Thirty studies reported cranial nerve impairments in patients with COVID-19. Markedly, 746 patients presented smell/taste impairment. Anosmia and dysgeusia/parageusia indicate early involvement of the PNS by SARS-CoV-2, allowing for early screening and isolation of suspected cases before the onset of respiratory symptoms. The neurotrophic properties of SARS-CoV-2 may facilitate access to the CNS through the olfactory nerve and explain why many patients have reported anosmia as a preceding symptom [37]. In COVID-19, the sudden olfactory loss is typically unrelated to nasal swelling or rhinitis [7, 38]. The prevalence of anosmia and ageusia ranges widely from 5% in a study of patients hospitalized in Wuhan to 88% of patients for a cohort study conducted in Germany [7, 12, 38]. Visual deficits reported in COVID-19 include hemianopia in patients with acute ischemic stroke [29, 39, 40] and optic neuritis with acute visual loss [22], associated with optic nerve contrast enhancement in magnetic resonance imaging (MRI). Oculomotor impairment was present in 14 patients, in isolation or as part of a Miller-Fisher syndrome [41, 42]. These patients presented with a compromise of the III, IV, and VI cranial nerves leading to ophthalmoparesis and diplopia. Uni or bilateral abducens' involvement associated with COVID-19 has been described [42, 43]. MRI studies confirmed nerve enhancement in some of them [44, 45]. Facial nerve compromise by SARS-CoV-2 can occur in isolation [46] or as part of peripheral neuropathy like Guillain-Barré syndrome (GBS) [47]. A group of patients presented with bilateral facial diplegia with unresponsive blink reflex or unilateral facial nerve palsy, around 10 days of SARS-CoV-2 infection [46, 47]. Usual MRI findings in these patients included facial nerve contrast enhancement [44]. Similarly, in some patients with GBS and cranial nerve impairment, III, VI, VII, and VIII contrast enhancement in MRI was evident [45]. Finally, some authors reported compromise of low cranial nerves among patients with COVID-19, including dysphagia as part of GBS [48], isolated dysphagia [49], and hypoglossal deficit due to rhombencephalitis [50].
In this review, 990 patients in 19 studies presented features compatible with acute encephalopathy. Encephalopathy may appear as the predominant disorder at the initial presentation of COVID-19, although most cases rarely progress to severe encephalopathy [30]. Many patients with a clinical diagnosis of encephalopathy had no brain imaging findings. Transmission electron microscopy studies performed postmortem in patients with acute encephalopathy revealed viral particles within cytoplasmic vacuoles of brain capillary endothelial cells in frontal lobe sections. Reverse transcription polymerase chain reaction (RT-PCR) testing of frozen tissue confirmed the presence of SARS-CoV-2 in the brain [51]. The frontal lobe compromise could explain the behavioral changes seen in some patients, and the viral particles in endothelial cells may support a hematogenous dissemination pathway on SARS-CoV-2 into the CNS. Four patients with confirmed COVID-19 presented acute hemorrhagic necrotizing encephalopathy, with findings associated with disrupting mechanisms of the blood-brain barrier that could be related to cytokine storm [28, 52, 53]. Four additional patients presented clinical and imaging features of posterior reversible encephalopathy syndrome (PRES), with acute onset of headache, altered mental status, seizures, and visual disturbances accompanied by fluctuations of blood pressure, with hemorrhagic complications [22, 54]. A multifactorial series of mechanisms related to SARS-CoV-2 infection, along with a breakdown of the blood-brain barrier, may contribute to PRES development in susceptible patients. In our review, EEG findings in several patients with acute encephalopathy included diffuse or focal (frontal or frontotemporal) slow activity wave patterns and some rhythmic discharges [22, 26, 30, 55,56,57,58].
Neuroinflammatory disorders
In our review, 23 patients (in 17 studies) had confirmed CNS inflammatory lesions, including encephalitis, meningoencephalitis, and encephalomyelitis, with variable prevalence [5, 22, 28, 37]. In a cohort of 2660 hospitalized COVID-19 patients, six patients presented with encephalitis as the first and only disorder, two with fatal outcomes [5]. In another cohort of 841 patients, only one patient had confirmed encephalitis [22]. The CSF of patients with inflammatory lesions showed elevated proteins, with an average of 196.3 mg/dl (range of 19–466 mg/dl) and increased cellularity, with 28.95 cells/μL (range 0–115 cell/μL). Most of these patients had normal glucose levels on CSF, although four patients had slightly increased CSF/serum glucose ratio [28, 29, 59]. The isolation of SARS-CoV-2 was possible only in three CSF samples [32, 60, 61]. Several authors reported that CSF cellularity was predominantly lymphocytic [29, 32, 59, 62], reaching 100% lymphocytes in one case [61]. Proinflammatory cytokines in CSF measured in six patients showed high levels of interleukin (IL) 6–8, IP-10, monocyte chemoattractant protein-1 (MCP-1), neurofilament light polypeptide (NFL), glial fibrillary acidic protein (GFAP), tumor necrosis factor-alpha (TNF-α), and B-2 microglobulin [56, 59, 62, 63]. CSF samples of 20 patients with CNS compromise, and four with PNS involvement, ruled out concomitant or alternative infections. Ischemic neuronal damage, demyelination, and viral RNA in and around the hippocampus allowed the confirmation of encephalopathy in a patient who underwent brain biopsy [64]. Other neuropathology findings included perivascular lymphocytes and focal leptomeningeal inflammation. Immunohistochemical analysis showed no cytoplasmic viral staining. Brain sections from five different patients expressed low levels of the virus, but positive tests could be explained by in situ virions or bloodstream viral RNA [65]. EEG studies in patients with neuroinflammatory disorders showed generalized slow-wave activity patterns [61, 62, 66].
Acute cerebrovascular disease
Twenty studies reported 615 patients with acute stroke. Among COVID-19 patients, the reported prevalence of acute ischemic stroke ranged between 1.1 to 2,5%, increasing to 11 to 31% among those with neurological compromise. The mean time of stroke occurrence was 10 days after the onset of COVID-19 symptoms, although other studies reported an occurrence as early as 2 days after clinical onset [67]. Although the occurrence of cerebrovascular disease induced a two-fold increased risk of a severe form of COVID-19, it did not directly correlate with a significant increase in mortality [68]. Thromboembolic events were the most common neuroimaging finding associated with COVID-19 in this review, including 184 events of acute ischemic strokes. Most of the cases had atypical characteristics, such as multiple arterial territories affected without an identified cardioembolic source, bilateral compromise, a high proportion of vertebrobasilar stroke, arterial dissection, and vasculitis [22, 69, 70]. Most patients presenting COVID-19 associated stroke had baseline cardiovascular risk conditions such as hypertension, diabetes mellitus, hyperlipidemia, smoking, or previous stroke history [13]. In neuropathology findings of selected cases, a few microscopic infarcts were apparent in the neocortex. Hippocampus and cerebellum had scattered necrotic neurons, indicating terminal hypoxic-anoxic injury. Regional infarcts, however, were not present in the brain, brainstem, or spinal cord. T-cells were present surrounding blood vessels and lesions, contrasting with no B cell activation. These non-specific findings can be due to vascular impairment, inflammatory/demyelinating processes, or a combination of mechanisms with direct endothelial cell damage and excessive cytokines release [71]. For hemorrhagic stroke, the estimated prevalence ranged between 0.4 to 2.4%. In this review, 40 patients presented hemorrhagic stroke, 66.5% of which were on anticoagulation therapy [72], and one patient reportedly had a ruptured aneurysm [73]. The fact that SARS-CoV-2 binds explicitly to ACE2 receptors, along with thrombocytopenia observed in severe cases, may lead to an increased risk of a cerebral hemorrhage [13]. Postmortem examinations of selected cases revealed mild brain swelling and foci of white matter hemorrhagic lesions central fibrin with associated extravasated red blood cells, with surrounding reactive gliosis. All lesions presented macrophages at the periphery, axonal damage, and myelin loss. In patients with stroke, CSF studies showed an average protein level of 50 mg/dL; SARS-CoV-2 in CSF was positive in only one case [27, 73]. EEG findings in patients with acute stroke were described only for two patients in one study, one of them demonstrated bilateral slowing of the background rhythm with sharp frontal waves, and the other one showed persistence of sharp slow waves, mainly over the left-hemispheric regions [27].
Peripheral neuropathies
Fifteen studies reported 22 patients infected with SARS-CoV-2 and GBS, while three studies reported three patients with Miller-Fisher syndrome and one patient with polyneuritis cranialis [41, 42, 44]. The prevalence of GBS accounted for approximately 0.5% of COVID-19 patients, who developed the clinical features between 5 to 10 days after the acute onset of respiratory symptoms [46, 74]. Whittaker et al. suggested that GBS could be a significant neurological sequela of SARS-CoV-2 [12], whereas other authors imply that GBS may occur in patients with COVID-19 without any preceding respiratory or systemic symptoms [48]. Most case reports describe patients presenting with marked lower limb weakness over upper limbs and areflexia that occurred acutely or subacutely. Variable sensory abnormalities have also been described [12]. Nerve conduction and electromyography studies carried out in 16 patients with GBS and COVID-19 reported acute inflammatory demyelinating polyneuropathy in 12 cases [45, 48, 74,75,76,77,78,79,80,81], sensory-motor axonal neuropathy in 3 cases [74, 82], and acute motor axonal neuropathy in 1 case [7]. Three patients with GBS presented enhancement of the caudal nerve roots on spine MRI [44, 74]. Sixteen studies reported CSF findings in 22 patients with SARS-CoV-2-related PNS manifestations. The main findings were albuminocytological dissociation with an average of proteins of 96,6 mg/dL and white cell counts ranging from 0 to 9 cells/μL, without other pathologic findings. SARS-CoV-2 tests were negative in all the CSF samples [41, 42, 45, 46, 74, 75, 79,80,81]. Concomitant Campylobacter jejuni infection and Lyme disease were also ruled out [48, 77].
To date, this is the most comprehensive systematic review of the central and peripheral involvement of the nervous system by COVID-19 and the only one that integrally assesses the pathophysiology and clinical features, as well as the neuropathology, neuroimaging, electrophysiology, and CSF findings altogether, to analyze their impact in the clinical scenario. Previously reported systematic reviews included a more limited number of articles, ranging between 31 to 37 studies [12, 13]. In many publications, the clinical features and paraclinical findings were siloed and not grouped as nosological entities accounting for the neurological involvement of COVID-19.
In our review, critical neurological events were more frequent among patients with a severe infection than those with mild disease [70]. Patients with COVID-19 admitted with respiratory compromise only, who developed neurological conditions, tended to progress with a more severe course, with increased intubation and mechanical ventilation requirements [83]. Notwithstanding, mortality rates were more associated with the severity of the systemic compromise rather than the neurological involvement.
In most cases in this review, neurological manifestations of COVID-19 resulted from acute nervous system involvement by SARS-CoV-2. Although we cannot establish a causal association between having a history of a neurological condition and increased risk of developing neurological compromise after SARS-CoV-2 infection, in some cases, COVID-19 prompted acute neurological manifestations or exacerbated baseline neurological conditions. For instance, COVID-19 increased the risk for uncontrolled seizures in patients with epilepsy [7, 23, 25, 84], delirium in neuropsychiatric disorders (major neurocognitive disorder, dementia with Lewy-bodies, and schizophrenia) [18], and multiple sclerosis exacerbations [44].
In this review, CNS involvement was more frequent than PNS compromise. Potential explanations include increased brain vulnerability to hypoxia compared to peripheral nerves [85, 86] and a greater expression of ACE2 receptors in the neurons' soma than in axons and dendrites [87]. The specific mechanisms by which SARS-CoV-2 may affect the nervous system are still debatable. However, there is evidence that combined direct and indirect mechanisms play a role in developing CNS and PNS involvement in patients with COVID-19. This review allowed us to categorize the different pathophysiological processes described below.
Neurotropic properties of SARS-CoV-2
Specific neurologic manifestations are attributable to the neurotropic mechanisms of SARS-CoV-2, demonstrated by electron microscopy, immunohistochemistry, RT-PCR in brain tissue from autopsy specimens, and CSF tests [2, 3, 32, 51, 88]. Propagation can occur through neuronal dissemination, in which the virus would initially infect the PNS and spread until it gains access to the CNS. Anosmia, a frequent symptom in patients with COVID-19, could be an early indication of this pathway [2]. The mechanisms involved may include retrograde or anterograde neuronal transport through the motor proteins dynein and kinesins [89]. SARS-CoV-2 could gain access through the olfactory bulb and the uncinate fasciculus; it would directly reach the anterior cingulate and the basal forebrain [18, 90]. Brainstem involvement can also occur after exposure to human coronaviruses through the nasal cavity [2, 14].
Damage to microvasculature
The spike protein S1 enables the virion's attachment to the angiotensin-converting enzyme 2 (ACE2) receptor, enabling the attachment to the cell membrane [3, 88]. S1 protein in SARS-CoV-2 has 10 to 20 times more affinity for the ACE2 receptor than other coronaviruses. This characteristic might lead to virion's attachment to the cerebral capillary walls after hematogenous dissemination, followed by a distortion of the blood-brain barrier and viral access to the brain tissue [3, 88]. As the virus gains access to cerebral microcirculation, it can create a hypercoagulability state that may slow the cerebral circulation flow, allowing for increased interaction between the virus and the ACE2 receptors [26]. Glial cells, as well as neurons, express ACE2 receptors; therefore, the attachment of the virus to the receptor could contribute to its neurotropism, which, in turn, could initiate a replication cycle with neural cell damage [3, 88]. SARS-CoV-2 can also cause endothelial damage in the nervous system due to direct infection, activation of the immune system, and thrombo-inflammatory response, leading to microvascular and macrovascular thrombotic events [71, 91]. Given that the glycocalyx covers the entire vascular endothelium, its disruption exposes the endothelial cells to oxidative damage, affecting the microvascular tone and endothelial permeability, maintenance of the oncotic gradient, leukocyte adhesion and migration, and inhibition of intravascular thrombosis [92].
Brainstem compromise
Animal studies identified the brainstem as a usual target for SARS-CoV. Similarly, cardio-respiratory malfunction in patients with COVID-19 could be due to brainstem impairment by the virus [2, 88, 90]. The brainstem's compromise can also explain other symptoms such as nausea, loss of appetite, and vomiting in COVID-19 patients. Autonomic nervous system dysregulation relates to brainstem regions such as the solitary tract's nucleus and the hypothalamus, both parts of the dorsal vagal complex. This abnormality may explain nausea, vomiting, and inappetence described in the disease's early stages [21].
Neuroinflammatory response
One way the SAR-CoV-2 can get access to cerebral circulation is by meddling with the immune response. Most of the coronaviruses that affect humans tend to infect the mononuclear phagocytes, leading to the hypothesis that the virus manipulates innate immune response to create a reservoir to access the bloodstream [2, 93]. Endothelial ACE2 receptors' use to attach to the cell can initiate a coagulation cascade, potentially predisposing patients to microthrombi, acute clots, and stroke [18, 88]. Another mechanism from which SARS-CoV-2 can generate brain damage is by creating a secondary encephalopathy due to inflammation or other systemic viral effects [4, 18], such as cerebral hypoxia or immune dysregulation [15]. Furthermore, SARS-CoV-2 can incite proinflammatory cytokines' activation in promoting blood-barrier breakdown, especially IL-8 and monocyte chemoattractant protein-1 [26]. Also, the increase in inflammatory markers can create a local cortical irritation that might initiate seizures [26].
SARS-CoV-2 can invade hematopoietic cells and induce a low expression of antiviral cytokines like type I interferon (IFN-αβ) and overexpression of proinflammatory cytokines like TNF-α and IL-6, as well as some chemokines [94]. Besides, a study showed that severe infection by SARS-CoV-2 could create lymphopenia with decreased CD4+ and CD8+, but interestingly, there is no decrease in lymphocytes B. In summary, there is an increase in cytokines IL6, IL2R, IL10, TNFα, and MCP-2 production and a decrease in IFN-γ production [95]. The resulting cytokine storm can create brain dysfunction and prompt neurological symptoms [5]. In other diseases, inflammatory cytokines passing the blood-brain barrier are a causal mechanism of encephalopathy and a significant systemic inflammatory response that could lead to a cytokine storm with a blood-brain barrier breach [18]. Patients with COVID-19 can also have high levels of IL-8 and IL-10 in CSF [59]. This high cytokine concentration in CSF samples may favor the neuroimmunological theory suggested by several authors, which propose that cytokine-mediated damage could be the leading cause of neurological impairment, rather than direct pathogenicity of the virus on the CNS [7, 20, 22, 62, 96].
Autoimmune response
SARS-CoV-2 spikes interact with the GM1 ganglioside in peripheral nerves, resulting in cross-reactivity and antibody production against these antigens, inducing the peripheral demyelination patterns seen in GBS [97]. Infectious diseases caused by Campylobacter jejuni, Zika virus, and cytomegalovirus show similar molecular mimicry [98]. However, the lack of detection of SARS-CoV-2 in CSF samples may indicate that there is no active intrathecal replication that explains direct demyelination [97]. A systemic inflammatory storm in COVID-19 may also contribute to the amplification of the GBS's dysimmune process, related to increased blood inflammatory markers (e.g., CRP, IL-6, TNF-α, and IL-1) [99]. On the other hand, neuroinvasion by SARS-CoV-2 may favor leakage of CNS antigenic epitopes (such as aquaporin peptides) to the systemic circulation, leading to autoimmune responses. Although the exact pathogenesis of acute disseminated encephalitis (ADEM) in patients with COVID-19 is still unknown [66, 71], previous research demonstrated cross-activation of antibodies and self-sensibilization of T-cells against myelin related to several bacterial and viral infections, including coronaviruses [100].
Demyelination
Human coronaviruses that infect the CNS can create a chronic infection and progressive demyelination of the brain, similar to multiple sclerosis [2]. The combination of demyelinating lesions and traces of coronavirus in brain tissue from autopsies and in CSF could explain part of the neuronal compromise of SARS-CoV-2 [101]. SARS-CoV-2 may affect white matter due to various mechanisms, including hypoxia [102], direct injury due to viral neurotropism [102], and autoimmune response combined with endothelial dysfunction [103], which can lead to clinical pictures or imaging compatible with ADEM, neuromyelitis optica spectrum disorder, or multiple sclerosis [66, 71, 104, 105].
Systemic hypoxia
Severe pneumonia seen in COVID-19 could lead to brain compromise due to hypoxemia caused by the diffuse alveolar damage and inflammatory exudate [106]. These phenomena contribute to vasodilatation, hypercarbia, hypoxia, and anaerobic metabolism, inducing cellular and interstitial edema, low cerebral flow blood, and ischemia [89, 106, 107]. Neuropathology findings support these mechanisms by describing a hypoxic injury to the cerebrum and cerebellum without associated thrombi or vasculitis [65]. Also, SARS-CoV-2 can cause a reduction in dyspnea perception by the indirect toxic effect of cytokines in the corticolimbic circuits and direct effect by affecting ACE2 receptors in cardiorespiratory center neurons in the brainstem [108, 109]. Therefore, COVID-19 may cause a rapidly progressive central respiratory insufficiency, presenting clinically as patients without evident dyspnea despite low blood oxygen levels, aggravating hypoxemia, and prompting early ventilation [87, 108].
Both the central and the peripheral nervous systems may act as a permanent target tissue for neuroinflammatory processes, which has led to theorizing that SARS-CoV-2 infection may trigger or worsen neurodegenerative disorders [94]. COVID-19 infection in children and adolescents may modify long-term cognoscitive capacities and increase the risk of psychiatric disorders because of the cytokine storm effects in the central nervous system [94]. For COVID-19 survivors with specific neurodegenerative disorders such as Alzheimer's, Parkinson's disease, multiple sclerosis, and mood disorders, a neuroinflammatory component may play a role in chronic deterioration. Therefore, long-term follow-up of cognoscitive and psychiatric status should be indicated [94].
Very few publications address the therapeutic approach to CNS and PNS involvement in patients with COVID-19. However, there appears to be consensus on the early recognition and timely treatment of these patients. For instance, delirium requires specific and timely therapeutic measures to decrease its impact on the short- and long-term patient's clinical course [110]. Likewise, the appearance of clinical or subclinical seizures in patients with COVID-19 should prompt starting antiseizure medication since untreated isolated seizures may escalate to non-convulsive status epilepticus, leading to higher morbidity and mortality [35]. Furthermore, a high index of suspicion can lead to early detection and timely treatment of neurological conditions such as stroke, encephalopathy, neuroinflammatory disorders, and peripheral neuropathies.
We acknowledge some limitations in this systematic review, including selection bias since our search algorithm included only publications specifically reporting patients with CNS and PNS involvement. Valuable articles with general descriptions of COVID-19 but not explicitly focused on neurological involvement might contain a significant number of patients with neurological manifestations. Besides, most of the scientific evidence available so far originates in observational and descriptive studies. Although we found a significant number of patients with COVID-19 with neurological manifestations, only a small proportion reported neuroimaging, CSF, electrophysiology, and neuropathology findings. This fact might be related to the scarce but ongoing knowledge generated in scientific publications worldwide as the pandemic progresses. International collaborative efforts and exhaustive neurological registries will enhance the translational knowledge of COVID-19's CNS and PNS involvement and generate therapeutic decision-making strategies [111, 112].
This systematic review presents a comprehensive overview of the scientific literature regarding the central and peripheral nervous system's involvement by COVID-19 and the diverse manifestations in terms of clinical and paraclinical findings. Our synthesis process led to a categorical analysis of the CNS and PNS involvement for all patients included and provided a comprehensive explanation of the reported pathophysiological mechanisms for which SARS-CoV-2 infection may cause neurological impairment. There is a need to conduct prospective cohort studies to analyze the mid and long-term consequences of the CNS and PNS involvement by COVID-19 and randomized clinical trials assessing the efficacy of treatments targeting the neurological compromise by this devastating condition.
The dataset and raw data supporting the conclusions of this article are available at Intellectum a publicly available, recognized institutional repository owned by Universidad de La Sabana. They can be accessed at http://hdl.handle.net/10818/44055
ACE2:
Angiotensin-converting enzyme 2
ADEM:
Acute disseminated encephalitis
CNS:
CSF:
EEG:
GBS:
Guillain-Barré syndrome
GFAP:
Glial fibrillary acidic protein
IFN:
IL:
Interleukin
MCP:
Monocyte chemoattractant protein
MRI:
Neurofilament light polypeptide
PNS:
Peripheral nervous system
PRES:
Posterior reversible encephalopathy syndrome
RT-PCR:
SARS-CoV:
Severe acute respiratory syndrome coronavirus
SARS-CoV-2:
Severe acute respiratory syndrome coronavirus 2
TNF:
Tumor necrosis factor
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Ehrenfeld M, Tincani A, Andreoli L, Cattalini M, Greenbaum A, Kanduc D, et al. Covid-19 and autoimmunity. Autoimmun Rev. 2020;19(8):102597. https://doi.org/10.1016/j.autrev.2020.102597.
Costela-Ruiz VJ, Illescas-Montes R, Puerta-Puerta JM, Ruiz C, Melguizo-Rodríguez L. SARS-CoV-2 infection: The role of cytokines in COVID-19 disease. Cytokine Growth Factor Rev. 2020;54:62–75. https://doi.org/10.1016/j.cytogfr.2020.06.001.
Esposito S, Di Pietro GM, Madini B, Mastrolia MV, Rigante D. A spectrum of inflammation and demyelination in acute disseminated encephalomyelitis (ADEM) of children. Autoimmun Rev. 2015;14(10):923–9. https://doi.org/10.1016/j.autrev.2015.06.002.
Matías-Guiu J, Gomez-Pinedo U, Montero-Escribano P, Gomez-Iglesias P, Porta-Etessam J, Matias-Guiu JA. Should we expect neurological symptoms in the SARS-CoV-2 epidemic? Neurologia. 2020;35(3):170–5. https://doi.org/10.1016/j.nrl.2020.03.001.
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Pinto AA, Carroll LS, Nar V, Varatharaj A, Galea I. CNS inflammatory vasculopathy with antimyelin oligodendrocyte glycoprotein antibodies in COVID-19. Neurol Neuroimmunol neuroinflammation. 2020;7(5):e813. https://doi.org/10.1212/NXI.0000000000000813.
Zhang T, Rodricks MB, Hirsh E, Wood R, Somerset H, Ave R. COVID-19-Associated Acute Disseminated Encephalomyelitis – A Case Report. Preprint at MedRxiv. 2020:1–7.
Ghosh R, De K, Roy D, Mandal A, Biswas S, Biswas S, et al. A case of area postrema variant of neuromyelitis optica spectrum disorder following SARS-CoV-2 infection. J Neuroimmunol. 2021;350:577439. https://doi.org/10.1016/j.jneuroim.2020.577439.
Abboud H, Abboud FZ, Kharbouch H, Arkha Y, El Abbadi N, El Ouahabi A. COVID-19 and SARS-Cov-2 infection: pathophysiology and clinical effects on the nervous system. World Neurosurg. 2020;140:49–53. https://doi.org/10.1016/j.wneu.2020.05.193.
Ahmad I, Rathore FA. Neurological manifestations and complications of COVID-19: a literature review. J Clin Neurosci. 2020;77:8–12. https://doi.org/10.1016/j.jocn.2020.05.017.
Li Z, Liu T, Yang N, Han D, Mi X, Li Y, et al. Neurological manifestations of patients with COVID-19: potential routes of SARS-CoV-2 neuroinvasion from the periphery to the brain. Front Med. 2020;14(5):533–41. https://doi.org/10.1007/s11684-020-0786-5.
Nouri-Vaskeh M, Sharifi A, Khalili N, Zand R, Sharifi A. Dyspneic and non-dyspneic (silent) hypoxemia in COVID-19: possible neurological mechanism. Clin Neurol Neurosurg. 2020;198:106217. https://doi.org/10.1016/j.clineuro.2020.106217.
Kotfis K, Williams Roberson S, Wilson JE, Dabrowski W, Pun BT, Ely EW. COVID-19: ICU delirium management during SARS-CoV-2 pandemic. Crit Care. 2020;24(1):176. https://doi.org/10.1186/s13054-020-02882-x.
Román GC, Reis J, Spencer PS, Buguet A, Öztürk S, Wasay M, et al. COVID-19 international neurological registries. Lancet Neurol. 2020;19(6):484–5. https://doi.org/10.1016/S1474-4422(20)30148-4.
The Lancet Neurology TL. The neurological impact of COVID-19. Lancet Neurol. 2020;19:471. https://doi.org/10.1016/S1474-4422(20)30142-3.
Universidad de La Sabana entirely funded the study and had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit it for publication.
Translational Neuroscience Research Lab, Faculty of Medicine, Universidad de La Sabana, Autopista Norte, KM 7, Chía, 250001, Colombia
Juan I. Guerrero, Luis A. Barragán, Juan D. Martínez, Juan P. Montoya, Alejandra Peña & Kemel A. Ghotme
Translational Neuroscience Research Lab, Clinical Neurology Program, Universidad de La Sabana, Autopista Norte, KM 7, Chía, 250001, Colombia
Fidel E. Sobrino
Neurology Unit, Hospital Occidente de Kennedy, Bogota, Colombia
Pediatric Neurosurgery, Pediatric Epilepsy Surgery, Neurosurgical Laser Ablation Program, Upstate University Hospital, 750 East Adams Street, Syracuse, NY, 13210, USA
Zulma Tovar-Spinoza
Pediatric Neurosurgery, Department of Neurosurgery, Fundacion Santa Fe de Bogota, Bogota, Colombia
Kemel A. Ghotme
Juan I. Guerrero
Luis A. Barragán
Juan D. Martínez
Juan P. Montoya
Alejandra Peña
JIG, LAB, JDM, JPM, and AP participated in the study design, investigation procedures, formal analysis, review, and editing. FES and ZTS participated in the results' formal analysis and the manuscript's review and editing. KAG conceptualized the original idea and study design, supervised the investigation, methodology, formal analysis, and validation procedures, wrote the original draft, and led the manuscript's review and editing. The author(s) read and approved the final manuscript.
Correspondence to Kemel A. Ghotme.
The authors declare that they have no conflict of interest.
Guerrero, J.I., Barragán, L.A., Martínez, J.D. et al. Central and peripheral nervous system involvement by COVID-19: a systematic review of the pathophysiology, clinical manifestations, neuropathology, neuroimaging, electrophysiology, and cerebrospinal fluid findings. BMC Infect Dis 21, 515 (2021). https://doi.org/10.1186/s12879-021-06185-6
Central and peripheral nervous system
Cerebrospinal fluid findings


text:
GLOBAL NEWS 1 - Canada
Canada's New National/Local News Channel (September 2014)
Mouseboy33 24 September 2014 1:00am
Following the launch of BC1, its 24 hour local news channel for British Columbia, Shaw Media plans on launching a national news channel with a twist.
Using its existing newsrooms across the country this news channel will present local news cut-ins at the top of the hour and a continuous data feed of hyper-local headlines and community events for each market. With the ability to cover live, breaking news at the local, regional or national level, Global News 1 will be like no other service on the dial.
So essentially viewers in Toronto will get a Toronto specific cut-in at the top of the hour and see Toronto local headlines, traffic and weather scrolling on the screens continuously even after the cut-in ends and returns to the national feed, all the while viewers in Calgary and Edmonton will get a market specific feeds on their screens. (Sorta seems how the Weather Channel uses its cable headends to feed specific weather data, forecasts and warnings on screen to 1000s of markets across the US whilst the national feed plays-out.)
This will result in 12 or more specific feeds across the country. Global also plans to create newsrooms in undeserved cities like Charlottetown PEI and create partnerships with independent stations in other cities such as on St Johns NFLD.
Sounds pretty cool and different from the current all news channels that exist in Canada like CBC News Network, CTV News Channel and the existing local news channels CP24 (Toronto) and Global's BC1 (British Columbia).
Global says that the channel will use BC1 as the launching point for the network if approved by the CTRC.
http://globalnews.ca/news/1575986/shaw-media-announces-proposal-for-24-hour-channel-global-news-1/
bakamann 28 September 2014 4:21am
Can anybody please explain to me with CTRC, and why is it every channel that wants to air in Canada needs to be approved by the authority... and Why the channel needs to be Part-Canadian-owned?
WW Update 28 September 2014 4:34am
bakamann posted:
These are essentially protectionist measures designed to prevent Canada -- particularly Anglophone Canada -- from being completely drowned out by the huge U.S. media market next door. That's why CTRC regulation has historically been rather heavy-handed.
Last edited by WW Update on 28 September 2014 4:44am - 2 times in total
Kevizz MS and Independent gave kudos
Independent 28 September 2014 9:08am
The CRTC is a regulatory body that is like the FCC in the US or Ofcom in the UK. Broadcasters are required to have licences to operate just like any other business. And yes, the CRTC is much more protectionist compared to the other regulators because most Canadians prefer content produced by the US industry over home-made programming. US TV shows consistently beat Canadian-produced shows in ratings with some exceptions during the year.
As for ownership, it's protectionism again. Many channels use names from the US such as CMT or Food Network through licensing agreements but are completely owned by Canadians or Canadians own a majority of that channel.
With that said, many non-Canadian channels are licensed to air in Canada. Basic cable/satellite packages offer the big 5 US terrestrial networks and we're offered many foreign news channels such as BBC WN, AJE, CNN/US, FNC, MSNBC, RT, etc. Foreign language channels from other countries are also available. None of these channels feature Canadian Content nor are they Canadian-owned.
WW Update gave kudos
This was first archived on 27 March 2015

redpajama_set_name: RedPajamaCommonCrawl


A three-day joint World Bank/FAO Appraisal Mission to the Nigeria Erosion and Watershed Project (NEWMAP) for Additional Financing (AF) commenced on Thursday, April 26, 2018 in Abuja. The mission is to ascertain readiness for implementation, agree on a clear implementation timeline and prepare for negotiations.
Some 19 NEWMAP participating states and Environment Commissioners in such states, state Newmap Project Coordinators and their key personnel are in Abuja working with the Supervising Ministry of Environment and Federal Project Management Unit (FPMU) on the modalities and specific project activity plans for the additional financing.
The multi-sectoral and multi-scale programme having the Project Development Objective (PDO) to reduce vulnerability to soil erosion in targeted sub-watersheds came into effectiveness in September 2013 with an initial seven south-eastern states of Abia, Anambra, Cross River, Ebonyi, Edo, Enugu and Imo (now referred to as first mover states) with acute gully erosion challenges. The project addressed 21 active gully sites across the first mover states for remediation.
The progress recorded by these initial seven states led to the attraction of other states and, in September 2015, additional seven states – Delta, Gombe, Kogi, Kano, Plateau, Oyo and Sokoto – joined the project having met the necessary selection criteria.
The third batch of states includes Akwa Ibom, Borno, Katsina, Nasarawa, and Niger, thus making a total number of 19 states in the project.
Five years thereafter, the 21 sites intervention is about 85 percent completion and about 682 hectares (ha) of targeted land treated for erosion with selected measures in targeted sub-watershed have been recovered. New sites have been prioritised and ranked based on risk to human life, catchment area, ease of maintenance, current structural defects, and proximity to vital infrastructure (major road, water, gas, electricity, etc.).
"For a Project designed not to exceed 11 states in its lifetime now having 19 states and still under pressure by other states, the project must be doing something right," stated Salisu Dahiru, the National Project Coordinator.
He added: "In few years of NEWMAP, 14 sub-catchment management plans have been developed in Abia, Anambra and Cross-River States. Approximately 582 hectares (ha) have been rehabilitated in the seven initial project States.
"Truly, the project has achieved great milestones," acknowledges Ambassador Fidel Ayogu, Michael Okonkwo and Donatus Njoku, who are participating states commissioners in Enugu, Anambra and Ebonyi respectively. They all believed that this category "A" project has achieved evidence based results mostly across the first seven states.
Speaking on the appraisal mission Dr. Amos Abu, the Task Team Leader of NEWMAP, enjoined participants to look at the cost and agree on what is realistic and obtainable. He commended the team for preparing NEWMAP Additional Financing and stressed that NEWMAP is a flagship project and has achieved appreciable milestones.
NEWMAP is predicated on an eight-year Strategic Investment Loan (SIL) of $508.59 million, consisting of a $500 million International Development Association (IDA) concessional loan, blended with Global Environment Facility (GEF) Trust Fund, and Special Climate Change Fund (SCCF) grants totalling $8.59 million. The Government of Nigeria's contribution would amount to approximately $150 million (the Federal Government 60% and participating states 40%).


Next PostNext What happens when runDisney cancels a half marathon at Walt Disney World?
Otronicon, the annual four-day Orlando Science Center event celebrating technology, starts Friday, Jan. 13. Disney fans will find plenty to inspire them, including an interactive exhibit presented by Walt Disney World that takes participants behind the scenes of some of the resort's most popular attractions.
Now in its twelfth year, Otronicon has grown from a conference for video gamers to one that encompasses the many forms of technology that we use in our everyday lives. This year, an emphasis again has been placed on STEM (science, technology, engineering and mathematics) careers. Many, if not most, of the exhibitors are local companies with a vested interest in the development of STEM programs and jobs in Orlando.
Disney's Imagineers demonstrate "Storytelling through Technology" each day throughout the event. The exhibit promises to take visitors on a journey "through technology and time" that highlights "technologies used to bring the animated figures and visual effects featured at some of Walt Disney World's most iconic attractions and shows to life." Participants also can explore a "color and play" station, where they can add color to favorite Disney characters and then see them come to life through the use of augmented reality technologies.
Video games still make up a large part of the event, too. Families can take part in daily competitions hosted by Powder Keg Games; visit the Indie Game Showcase to discover the latest and most innovative game releases all in one place; and try a number of new and popular games. Otronicon 2017 also features state-of-the-art medical and military simulators from Florida Hospital for Children and Lockheed Martin, respectively. And participants can learn about new technology at Kennedy Space Center through several demonstrations.
Admission to Otronicon is $19.95 per day for adults; $17.95 per day for students and seniors; and $13.95 per day for children ages 3 to 11. Admission to Otronicon is free for Science Center members. Hours for Otronicon are 10 a.m. to 5 p.m. each day. A separate ticket is required for Science Night Live featuring Otronicon! From 8:30 to 11:30 p.m. Jan. 14.
Volunteer opportunities for those ages 13 and older still are available as well. The Science Center needs volunteers to serve as game techs, exhibit operators, way finders and more. Each shift lasts about four hours, and volunteers get free admission to the event on the days they volunteer and free Otronicon T-shirts. Sign up here or contact Zach Lynn, director of volunteers and engagement, at zlynn@osc.org or 407-514-2223.


When it comes to innovation in business, young people are blazing a trail.
With research from YouGov and Google showing that a quarter (22%) of young people aged between 15 and 18 are interested in starting their own business, young people are increasingly taking their careers into their own hands while giving the world something new, innovative and beneficial.
As we dive into 2017, there's no shortage of bold, brave and brilliant entrepreneurs with innovative ideas to make our living smarter and more sustainable. But, in order to realise their potential, these entrepreneurs need support.
One of the most prominent programmes designed to support eco-entrepreneurs is Shell LiveWIRE, which offers monthly start-up grants, coaching and online business support to 16 to 30 year-olds with innovative business ideas for a more sustainable future.
Its monthly Smarter Future Programme provides £5,000 funding to one winner each month, as well as the opportunity for all monthly winners to compete for the annual title of Shell LiveWIRE Young Entrepreneur of the Year and additional prize money worth £25,000.
Adaptavate is an environmentally-sustainable construction company that is rethinking and redesigning how the new generation of building materials are made. The company's first product, Breathaboard, is a bio-based alternative to plasterboard which helps to mitigate CO2-driven climate change by 'locking' carbon into the fabric of buildings.
Its founder, Tom Robinson, 28, came up with the idea while he was working as a builder and plasterer in Hackney, East London. With Breathaboard, Robinson is tackling two key problems in the building trade: the issue of 'unhealthy homes', where trapped moisture and condensation lead to poor air conditions, and the huge amount of waste generated by traditional construction, especially plasterboard, which is sent to a separate cell in landfill sites.
75% of Breathaboard is made from agricultural waste sourced from UK farmers, so it provides a renewable alternative to the 15 million tonnes of plasterboard that goes to landfill each year globally. In March 2016, Robinson was named Shell LiveWIRE's 'Young Entrepreneur of the Year' and awarded £30,000 to help scale-up Breathaboard.
Shell LiveWIRE also partnered with Adaptavate and WIRED in July 2016 for the Shell #makethefuture Accelerator, which brought some of the brightest minds in business and innovation to help Tom accelerate his business. Take a look at the highlights of the day here.
Solveiga Pakštaitė, Founder of Design By Sol, developed a bio-reactive food expiry label which indicates the condition of food inside its packaging.
Using gelatine to model the decay process of food, Bump Mark is able to indicate the food's condition when you run your finger over the label. A smooth surface means the food is fresh, while a layer of bumps, which occurs when the gelatine starts to break down, means the food is past its best and needs to be binned.
With over 15 million tonnes of good food thrown away in the UK each year, half of which comes from households, and with global food shortages soaring, Bump Mark offers a safe, recyclable, biodegradable, cheap and effective solution to prevent needless food waste.
Having originally designed Bump Mark while at university as a product that would help visually impaired consumers, Pakštaitė's product has captured the imagination of sighted consumers, too. In March 2015, having already won the James Dyson Award, Pakštaitė was crowned a Shell LiveWIRE Smarter Future Award winner, which allowed her to conduct the necessary testing to take Bump Mark from a concept to regulated food product. She also received an additional £5,000 as the winner of the Shell Staff Inspiration Award, having impressed Shell UK employees with her ingenuity, passion and entrepreneurial spirit.
Entomics, founded by Matt McLaren and three of his Cambridge University colleagues, is pioneering the transformation of food waste into sustainable sources of fuel for plants, animals and vehicles.
Using the larvae of the black soldier fly, Entomics converts food waste into a type of biodiesel to power vehicles and homes. The process, which is well known to gardeners whose compost is often produced with the help of soldier fly larvae, also creates high-protein animal feed and agricultural fertiliser as side-products. The eggs of the flies, which have life cycles of just five to eight days, hatch a few days after being laid beside rotten plant or animal matter, and are able to break down around 95% of the waste provided.
With around 40% of food waste generated in the UK currently disposed of via landfill, the burden of food waste on society is set to increase. Entomics wants to scale up their operation from addressing food waste in the UK to addressing food waste globally.
Having won the Shell LiveWIRE Smarter Future Award in September 2015, Entomics used the funding to buy a van to collect unwanted food from local supermarkets, including Sainsbury's, with whom Entomics has now established a partnership.
Edible Bug Farm is developing methods for sustainable farming by identifying high quality, cheap protein sources for the developing world: edible bugs.
It was while travelling in Asia, where insects are regularly eaten, that Adam Routledge came up with the idea for his business. Drawing on his background in biochemistry and ecology, Routledge and his co-founder, Matt Anderson, saw an opportunity to tackle three of the world's most pressing issues: food scarcity, resource demands, and greenhouse gases.
The UN estimates that 70% of the world's agricultural land and fresh water is currently dedicated to farming livestock. Yet for each 100kg of food a cow consumes, it only produces 4kg of meat and expells 100kg of methane gas every year, the equivalent to four tonnes of CO2. By contrast, crickets produce 47kg of meat per 100 kg of feed and have a negligible carbon footprint. With the world's population predicted to reach 9.6 billion by 2050, Edible Bug Farm offers a sustainable alternative to global farming practices.
Having won the Shell LiveWIRE Smarter Future Award in November 2015, Edible Bug Farm hopes to automate the farming process, reduce costs and help the company go to market. The team's ultimate goal is to shift UK perceptions of eating insects with the aim that, one day, bugs will become a mainstream part of our diets.
Every hour, the sun beams onto Earth more than enough energy to satisfy global energy needs for an entire year. Modern energy services are crucial to human well-being and to a country's economic development, and yet globally 1.2 billion people – 16% of the global population – live without access to electricity.
In response to this, CAVENTOU, founded by Marjan van Aubel and Thor Schuitemaker-Wichstrøm, created an exciting innovation in the field of solar energy, which uses colour to convert sunlight into energy.
Capitalising on a growing gap in the market, CAVENTOU developed the Current Table, a table that functions as a source of energy inside the home or in the office. The table's glass surface is entirely made of dye-sensitised solar cells that use the property of colour to create an electrical current. These solar cells are different to PV cells by working under diffuse light, making the Current Table the first piece of furniture that can harvest energy indoors. Without using any cables, the table becomes a portable renewable energy source that can charge devices like iPhones and iPads using USB ports, which are positioned on the side of the table.
CAVENTOU won funding from the Shell LiveWIRE Smarter Future Award programme in July 2015. The team is now looking to branch their technology out to new areas, such as windows.


text:
Myxomycetes: Biology, Systematics, Biogeography and Ecology
By Carlos Rojas Alvarado and Steven L. Stephenson
Science : Life Sciences - Biology - General | Science : Life Sciences - Ecology | Science : Life Sciences - Evolution | Science : Life Sciences - General
Digital Book format: PDF (Adobe DRM)
PDF (Adobe DRM) ePub (Adobe DRM)
Myxomycetes: Biology, Systematics, Biogeography, and Ecology is a comprehensive overview of the body of accumulated knowledge that now exists on myxomycetes. Its broad scope takes an integrated approach to the knowledge of this organismal group, considering a number of important aspects of their genetics and molecular phylogeny. It also treats myxomycetes as a distinct group from fungi, and includes molecular information that discusses the systematics and evolutionary pathways of the group. Additionally, biomedical and engineering applicability is discussed, thus expanding the audience and use of the book in a multidisciplinary context.
The book provides an authoritative resource for students, researchers and educators interested in the fields of protistology, microbial ecology, molecular microbiology, biogeography, mycology, biodiversity, and evolutionary biology, and will also interest the amateur naturalist and biologist.
Written in a simple, concise, and relatively non-technical style, allowing for a broad readership within biological, environmental and life science programs at academic and research institutions
Contains the comprehensive body of information available on myxomycetes under one cover, with contributions from the leading authorities in their respective topics
Provides straightforward, compiled information about myxomycetes and the potential of this group for basic and applied research
Formats and editions
PDF (Adobe DRM)
Myxomycetes: Biology, Systematics, Biogeography and Ecology PDF (Adobe DRM) can be read on any device that can open PDF (Adobe DRM) files.
Carlos Rojas Alvarado
Academic Press, August 2017
List Price: $99.95 eBook price: $92.99
Carlos Rojas Alvarado | Steven L. Stephenson
The Kingdom Fungi: The Biology of Mushrooms, Molds, and Lichens
Steven L. Stephenson
Mushrooms of the Southeast: Timber Press Field Guide
Todd F. Elliott & Steven L. Stephenson
ACOPS Yearbook 1986-87: Advisory Committee on Pollution of the Sea, London
Advisory Committee on Pollutio
PAES en Fiches, Santé Société Humanit
Nicolas Brault & Guillaume Vincenot
Cracking the AP Biology Exam, 2018 Edition: Proven Techniques to Help You Score a 5


Introducing the 2008 Toyota Avalon. This 4 door, 5 passenger sedan provides exceptional value! Under the hood you'll find a 6 cylinder engine with more than 250 horsepower, providing a smooth and predictable driving experience. The following features are included: a tachometer, variably intermittent wipers, power front seats, high intensity discharge headlights, telescoping steering wheel, power door mirrors, and air conditioning. Toyota ensures the safety and security of its passengers with equipment such as: dual front impact airbags with occupant sensing airbag, front side impact airbags, a panic alarm, and 4 wheel disc brakes with ABS. It also arrives with a Carfax history report, providing you peace of mind with detailed information. We pride ourselves in consistently exceeding our customer's expectations. Stop by our dealership or give us a call for more information.


You know how you can remember exactly where you were and what you were doing when some tragedy happened? I remember what I was doing when I found out about 9-11, when the Space Shuttle Challenger blew up in 1986, when the Columbine shooting happened, etc. Those events and so many more are embedded in my memory and on my psyche. It is truly instructive to see what Congress is up to regarding preventing gun violence when the deadliest act of gun violence in US history occurred.


text:
Home News All aboard with Téarma.ie
All aboard with Téarma.ie
A new version of www.téarma.ie, The National Terminology Database for Irish, was launched during Seachtain na Gaeilge at a launch event at Foras na Gaeilge headquarters today. The new website was developed by Fiontar & Scoil na Gaeilge, DCU with funding from Foras na Gaeilge.
www.téarma.ie is a platform for publishing the work of the Terminology Committee, a collection of terminology that covers a broad range of technical fields, from contemporary computing to traditional sailing. The database contains approximately 185,000 bilingual entries and has been one of the most widely-used Irish-language digital resources since its launch in 2006. Users of the site made over 7.5 million searches in the database in 2018.
The appearance of the website has been totally redesigned in a clean, contemporary style that is in keeping with other Foras na Gaeilge language resources. The new site has a responsive design, meaning that it will render well on a variety of devices or screen sizes.
The homepage now contains a feature that lists entries that have been recently added to the database, e.g. open top bus (bus oscailte), gealach na fola (blood moon), teorainn réidh (soft border) and tionchaire (influencer). Another new feature is the browsable domain list, providing a different way of querying the database.
Terms listed in the search results now have an additional feature which provides one-click access to searches in several other Irish-language resources (i.e. www.foclóir.ie, www.teanglann.ie, www.gaois.ie and Nua-Chorpas na hÉireann).
Foras na Gaeilge CEO, Seán Ó Coinn said, "For over 10 years, since the terminology website was made available to the public for the first time, Irish terminology and lexicography have dramatically changed in ways you would not expect in that short period of time. That transformation not only shows the linguistic expertise we have among us, but also reveals the technological expertise and partnership. Foras na Gaeilge has a very beneficial collaboration with third level institutions in relation to lexicography and terminology initiatives which allow us to make achievements that would not be possible for us to make alone. I would like to thank Fiontar & Scoil na Gaeilge DCU in particular in relation to this project. I would also like to thank members of The Terminology Committee for being so generous with their time and expertise; the result of their work can be seen on this new site."
Note for editor:
The following developments made on www.téarma.ie:
A multilingual terminology database containing approximately 185,000 concepts
Quick search providing exact results and related results
Advanced search for more specific queries
Browse by domain
Links to other language resources, i.e. foclóir.ie, teanglann.ie, gaois.ie, Nua-Chorpas na hÉireann
Terminology data available for download in TBX & TXT format
Terminology request form to make an enquiry to the Terminology Committee
Source code available under open licence
The new version of www.téarma.ie uses an onomasiological (or concept-based) approach with the search term being listed separately under each of the different concepts to which it refers. The previous version followed a semasiological (or dictionary-based) approach wherein the different meanings of a term were laid out under a headword. The main reason for this shift in emphasis is to differentiate more effectively between www.téarma.ie as a source for technical terms and online dictionaries which focus on general language.
In addition to the new features mentioned above, the terminology management system behind www.téarma.ie has been totally re-engineered. This is an essential aspect of the project that is not visible to the public but enables the effective storage and editing of the terminological data. 'Fiontar & Scoil na Gaeilge, DCU will launch Terminologue, a public, cloud-based version of this platform at www.terminologue.org in April 2019. This new resource will allow users to create, edit and publish their own termbases free of charge. In addition, the source code for both www.téarma.ie agus Terminologue will soon be published at github.com/gaois.
Anna Davitt, Programme Manager: Communications, Marketing & Awareness, Foras na Gaeilge
Tel: 0035387 673 6175
Email: adavitt@forasnagaeilge.ie
EBooks for the Business Sector
Soláthar seirbhís nuachta: Anailís ar thorthaí an tsuirbhé phobail
Cumasú & Cothú (Leabhrán Scéim Phobail Gaeilge)
Young Authors encouraged to publish
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