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Researchers report rare neurological condition in a few COVID-19 patients
Researchers in the United Kingdom and Italy have reported cases of COVID-19 where the patients later developed Guillain-Barre syndrome (GBS), a condition in which the patient’s own immune system attacks the nerves, leading to a weakness in the face or the extremities and even near-complete paralysis.
GBS typically emerges in the days and weeks following a respiratory or digestive tract infection, although it’s still unclear what causes the disorder.
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COVID‐19–associated Guillain‐Barré syndrome: The early pandemic experience
We reviewed 37 published cases of GBS associated with COVID‐19 to summarize this information for clinicians and to determine whether a specific clinical or electrodiagnostic (EDx) pattern is emerging. The mean age (59 years), gender (65% male), and COVID‐19 features appeared to reflect those of hospitalized COVID‐19 patients early in the pandemic. The mean time from COVID‐19 symptoms to GBS symptoms was 11 days. The clinical presentation and severity of these GBS cases was similar to those with non–COVID‐19 GBS. The EDx pattern was considered demyelinating in approximately half of the cases. Cerebrospinal fluid, when assessed, demonstrated albuminocytologic dissociation in 76% of patients and was negative for severe acute respiratory distress syndrome–coronavirus‐2 (SARS‐CoV‐2) in all cases. Serum antiganglioside antibodies were absent in 15 of 17 patients tested. Most patients were treated with a single course of intravenous immunoglobulin, and improvement was noted within 8 weeks in most cases.
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Guillain-Barré Syndrome with Facial Diplegia Related to
SARS-CoV-2 Infection
The incidence of GBS is approximately 1–2 cases per 100,000 people per year and changes in incidence may correspond with
exposure to infectious agents known to cause GBS.2 For example, during the 2015–2016 Zika virus epidemic, increases and decreases in GBS incidence worldwide coincided with increases and decreases in Zika virus disease incidence, with increases in
GBS incidence varying between 2 to 10 times the baseline. Nonetheless, GBS associated with Zika virus remained an
uncommon disorder. Although there is increasing evidence that GBS may occur secondary to COVID-19 and cases may be
underreported, the rate is likely consistent with that associated with other infectious diseases. As the COVID-19 pandemic
continues, GBS and other neurological manifestations of COVID-19 will continue to be characterized
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Guillain–Barré syndrome associated with SARS‐CoV‐2 infection. A systematic review
Most of the patients had a typical GBS clinical form predominantly with a demyelinating electrophysiological subtype. Mechanical ventilation was necessary in eight (44%) patients. Two (11%) patients died. Published cases of GBS associated with COVID‐19 report a sensorimotor, predominantly demyelinating GBS with a typical clinical presentation.
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Neurological associations of COVID-19
Although the predominant clinical presentation is with respiratory disease, neurological manifestations are being recognised increasingly.
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Neurological Complications: Present Findings and Future Predictions
The present outbreak caused by SARS-CoV-2, an influenza virus with neurotropic potential, presents with neurological manifestations in a large proportion of the affected individuals. Disorders of the central and peripheral nervous system are all present, while stroke, ataxia, seizures, and depressed level of consciousness are more common in severely affected patients. People with these severe complications are most likely elderly with medical comorbidities, especially hypertension and other vascular risk factors. However, postinfectious complications are also expected. Neurological disorders as sequelae of influenza viruses have been repeatedly documented in the past and include symptoms, signs, and diseases occurring during the acute phase and, not rarely, during follow-up. Postinfectious neurological complications are the result of the activation of immune mechanisms and can explain the insurgence of immune-mediated diseases, including the Guillain-Barré syndrome and other diseases of the central and peripheral nervous system that in the past occurred as complications of viral infections and occasionally with vaccines. For these reasons, the present outbreak calls for the introduction of surveillance systems to monitor changes in the frequency of several immune-mediated neurological diseases. These changes will determine a reorganization of the measures apt to describe the interaction between the virus, the environment, and the host in areas of different dimensions, from local communities to regions with several millions of inhabitants. The public health system, mainly primary care, needs to be strengthened to ensure that research and development efforts are directed toward right needs and directions. To cope with the present pandemic, better collaboration is required between international organizations along with more research funding, and tools in order to detect, treat, and prevent future epidemics.
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COVID-19–Associated Bifacial Weakness with Paresthesia Subtype of Guillain-Barré Syndrome
We report a case of bifacial weakness with paresthesia, a recognized Guillain-Barré syndrome subtype characterized by rapidly progressive facial weakness and paresthesia without ataxia or other cranial neuropathies, which was temporally associated with antecedent coronavirus 2019 (COVID-19). This case highlights a potentially novel but critically important neurologic association of the COVID-19 disease process. Herein, we detail the clinicoradiologic work-up and diagnosis, clinical course, and multidisciplinary medical management of this patient with COVID-19. This case is illustrative of the increasingly recognized but potentially underreported neurologic manifestations of COVID-19, which must be considered and further investigated in this pandemic disease.
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How COVID-19 can damage the brain
Some people who become ill with the coronavirus develop neurological symptoms. Scientists are struggling to understand why.
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Guillain-Barre syndrome during COVID-19 pandemic: an overview of the reports
Neurological manifestations were observed in 30% of the patients ofthe 2003 SARS2 outbreak.
Previously discovered types of coronavirus (SARS-CoV and MERS) and Zika virus have been associated with GBS as well.
The mechanism of the GBS incidence is based on molecular mimicry and anti-ganglioside antibodies after an infection in genetically predisposed patients.
These antibodies show the highest association with certain forms of GBS [26, 27]. A possible mechanism is an autoimmune reaction in which the antibodies on the pathogen, which are similar to the protein structures of the peripheral nerve components, lead to the damage of the nervous system [9]. This likeness has been termed “molecular mimicry” which is defined as the theoretical possibility that sequence similarities between foreign and self-peptides are enough to lead to the cross-activation of autoreactive B cell or T cell by pathogen-derived peptides.
At the time of writing this paper (Aug 2020), approximately 31 cases of GBS associated with COVID-19 infection have been reported. This study showed that, on average, 11.92 ± 6.20 days after COVID-19 infection, the neurological symptoms of GBS begin.
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The neurology of COVID-19 revisited: A proposal from the Environmental Neurology Specialty Group of the World Federation of Neurology to implement international neurological registries
SARS-CoV-2 has definitive neurogenic capacity.
After binding to ACE2 receptors in nasal epithelium it invades the olfactory nerve and bulb progressing to invade the brainstem respiratory centers.
Irreversible respiratory failure may be the reason for the dismal prognosis of COVID-19 respirator-dependent patients.
SARS-CoV-2 binds to ACE2 receptors in endothelial cells causing endotheliitis.
Stroke occurs as a result of the pro-thrombotic state caused by endotheliitis.
Multi-organ failure occurs secondary to virus invasion of ACE2 receptors in lung, kidney, intestines, and brain.
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From ‘brain fog’ to heart damage, COVID-19’s lingering problems alarm scientists
The likelihood of a patient developing persistent symptoms is hard to pin down because different studies track different outcomes and follow survivors for different lengths of time. One group in Italy found that 87% of a patient cohort hospitalized for acute COVID-19 was still struggling 2 months later. Data from the COVID Symptom Study, which uses an app into which millions of people in the United States, United Kingdom, and Sweden have tapped their symptoms, suggest 10% to 15% of people—including some “mild” cases—don’t quickly recover. But with the crisis just months old, no one knows how far into the future symptoms will endure, and whether COVID-19 will prompt the onset of chronic diseases.
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Guillain Barre syndrome associated with COVID-19 infection: A case report
In this report, we describe the symptoms of Guillain Barre syndrome (GBS) in one infected patient with COVID-19, for the first time. We reported a 65-years- old male patient with complaints of acute progressive symmetric ascending quadriparesis. Two weeks prior to hospitalization, the patient suffered from cough, fever, and RT-PCR was reported positive for COVID-19 infection. The electrodiagnostic test showed that the patient is an AMSAN variant of GBS. COVID-19 stimulates inflammatory cells and produces various inflammatory cytokines and as a result, it creates immune-mediated processes. GBS is an immune-mediated disorder and molecular mimicry as a mechanism of autoimmune disorder plays an important role in creating it. It is unclear whether COVID-19 induces the production of antibodies against specific gangliosides. Further investigations should be conducted about the mechanism of GBS in patients with COVID-19, in the future.
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Coronavirus Disease 2019 (COVID-19) Daily Research Briefs
July 14, 2020, Research Update
Guillain–Barré Syndrome Associated with SARS-CoV-2 in Italy. These authors report on five patients from three hospitals in northern Italy. Four of the patients developed lower limb weakness and paresthesias, and one developed facial diplegia followed by ataxia and then paresthesias. The patients were ultimately diagnosed with Guillain–Barré Syndrome. At the onset of neurologic symptoms, four of the patients had positive swabs for SARS-CoV-2, and the other eventually developed antibodies. None of the patients had a positive polymerase chain reaction in their cerebrospinal fluid. The development of Guillain–Barré Syndrome should not be a surprise because it has been frequently associated with viral infections and with active immunizations.
Written by Henry C. Barry, MD, MS, on July 9, 2020. (Source: Toscano G, Palmerini F, Ravaglia S, et al. Guillain-Barre syndrome associated with SARS-CoV-2. N Engl J Med. 2020;382(26):2574-2576.)
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Neurological complications of coronavirus infection; a comparative review
and lessons learned during the COVID-19 pandemic
Coronavirus disease-19 (COVID-19) pandemic continues to grow all over the world. Several studies
have been performed, focusing on understanding the acute respiratory syndrome and treatment strategies.
However, there is growing evidence indicating neurological manifestations occur in patients with COVID-19.
Similarly, the other coronaviruses (CoV) epidemics; severe acute respiratory syndrome (SARS-CoV-1) and
Middle East respiratory syndrome (MERS-CoV) have been associated with neurological complications.
Methods: This systematic review serves to summarize available information regarding the potential effects of
different types of CoV on the nervous system and describes the range of clinical neurological complications that
have been reported thus far in COVID-19.
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What Does COVID-19 Do to the Nervous System?
This relatively benign symptom wasn’t the focus of the weekly multidisciplinary meetings at the London-based National Hospital for Neurology and Neurosurgery that became the basis of Brown’s paper, which was published in Brain in July. Instead, the team discussed more severe, isolated cases of neurological dysfunction. Some of these signs are caused by a diverse range of conditions, but others, says Brown, are much rarer encounters.
Guillain-Barré syndrome, a severe but rare neurological syndrome caused by the body’s immune system attacking nerve cells outside the brain, has been noted repeatedly in COVID-19 patients. This is no small matter – symptoms include burning sensations in patients’ limbs and, in some cases, temporary paralysis and weakness. Guillain-Barré, says Brown, typically appears after bacterial or viral infection. The condition’s onset has been noted after cases of Zika virus or even influenza.
Other symptoms that severe COVID-19 shares with other conditions include psychiatric symptoms such as delirium, which Brown points out “is common in the context of fever or acute illness, particularly with increasing age.” When patients are put into intensive care and separated from their families in the height of a novel worldwide pandemic, it’s perhaps unsurprising that patients manifest confusion and fear.
But other symptoms are more unique to COVID-19 infection. “A number of things seemed more unusual,” says Brown. “We reported nine patients with acute disseminated encephalomyelitis (ADEM)-like illness over a short study period. We would not usually expect to see this disorder so frequently – in our paper we note that we would usually expect to see this number of patients over five months – suggesting that there may be an increased incidence of this in patients with COVID--19 infection.”
ADEM is an inflammatory disorder affecting the brain. A rush of immune cells into the central nervous system can lead to symptoms such as fever, fatigue, nausea and headache. But this incredibly rare condition is appearing in complex and damaging variants in some very ill COVID-19 patients. One case study from Brown’s paper, of a 47-year-old woman, detailed symptoms of acute hemorrhagic leukoencephalitis, a form of ADEM that involves bleeding and cell death within the brain. To treat this case, the team had to conduct a hemicraniectomy, where a flap of the skull is removed to relieve pressure on the swollen and inflamed brain. The patient, says the case study, thankfully continued to improve clinically after this procedure, but ADEM is no minor affliction.
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UB investigator’s research finds links between COVID-19 and neuromuscular disorders
Comprehensive review suggests virus can cause and exacerbate neuromuscular symptoms in some patients
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Guillain-Barré syndrome in SARS-CoV-2 infection: an instant systematic review of the first six months of pandemic
A systematic review from 1 January to 30 June 2020 revealed 42 patients with Guillain-Barré syndrome (GBS) associated with SARS-CoV-2 infection. Single cases and small series were reported from 13 countries, the majority from Europe (79.4%) and especially from Italy (30.9%). SARS-CoV-2 infection was demonstrated by nasopharyngeal swab (85.7%) and serology (14.3%). Median time between COVID-19 and GBS onset in 36 patients was 11.5 days (IQR: 7.7–16). The most common clinical features were: limb weakness (76.2%), hypoareflexia (80.9 %), sensory disturbances (66.7 %) and facial palsy (38.1%). Dysautonomia occurred in 19%, respiratory failure in 33.3% and 40.5% of patients were admitted in intensive care unit. Most patients (71.4%) had the classical clinical presentation but virtually all GBS variants and subtypes were reported. Cerebrospinal fluid (CSF) albumin-cytological dissociation was found in 28/36 (77.8%) and PCR for SARS-CoV-2 was negative in 25/25 patients. Electrodiagnosis was demyelinating in 80.5% and levels 1 and 2 of Brighton criteria of diagnostic certainty, when applicable, were fulfilled in 94.5% patients. Antiganglioside antibodies were positive in only 1/22 patients. Treatments were intravenous immunoglobulin and/or plasma exchange (92.8%) with, at short-time follow-up, definite improvement or recovery in 62.1% of patients. One patient died. In conclusion, the most frequent phenotype of GBS in SARS-CoV-2 infection is the classical sensorimotor demyelinating GBS responding to the usual treatments. The time interval between infectious and neuropathic symptoms, absence of CSF pleocytosis and negative PCR support a postinfectious mechanism. The abundance of reports suggests a pathogenic link between SARS-CoV-2 infection and GBS but a case-control study is greatly needed.
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COVID-19 and Guillain–Barré Syndrome: A Case Report and Review of Literature
During the recent coronavirus disease 2019 (COVID-19) outbreak in Northern Italy, we observed a 57-year-old man developing acute motor-sensory axonal neuropathy, a variant of Guillain–Barré syndrome (GBS), 12 days after severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection.
Several reports also suggested that GBS and Miller Fisher syndrome (MFS) could be neurological complications of COVID-19. Therefore, we performed a review of the 29 articles so far published, describing 33 GBS cases and five MFS cases associated with SARS-CoV-2 infection. We recommend awareness of this rare, but treatable, neurological syndrome, which may also determine a sudden and otherwise unexplained respiratory deterioration in COVID-19 patients.
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Neuropathogenesis and Neurologic Manifestations of the Coronaviruses in the Age of Coronavirus Disease 2019
A Review
Coronaviruses (CoV) are large, enveloped, positive-sense RNA viruses divided into 3 genera: alphacoronavirus, betacoronavirus, and gammacoronavirus.5 These viruses infect humans and numerous animal species, generally causing upper or lower respiratory tract, gastrointestinal, neurological, or hepatic disease.6,7 Currently, there are 7 CoV that can infect humans, including human coronavirus (HCoV)–229E, HCoV-NL63, HCoV-HKU1, HCoV-OC43, MERS-CoV, SARS-CoV-1, and SARS-CoV-2.8 Betacoronaviruses SARS-CoV-2, SARS-CoV-1, and MERS-CoV are associated with severe disease in humans.1,3,8 Although HCoV are typically associated with respiratory tract disease, 3 HCoV have been shown to infect neurons: HCoV-229E, HCoV-OC43, and SARS-CoV-1.
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Nineteen-year-old North Carolina university student in “tremendous shape” dies from COVID-19
On Monday, a 19-year-old college student at Appalachian State University in Boone, North Carolina, died from neurological complications after contracting COVID-19. Chad Dorrill, described as being in “tremendous shape” by his uncle, contracted the virus after his return to Boone for fall classes.
After developing flu-like symptoms, Dorrill returned home, where he tested positive on September 7. After quarantining for 10 days, and being cleared by his doctor, he returned to school. Soon afterward, he began suffering serious neurological problems. “When he tried to get out of bed his legs were not working, and my brother had to carry him to the car and take him to the emergency room,” his uncle, David Dorrill, told the New York Times. “It was a COVID complication that rather than attacking his respiratory system attacked his brain.”
Doctors suspect that COVID-19 triggered an undetected case of Guillain-Barré syndrome in Dorrill. Guillain-Barré causes the body’s immune system to attack nerve cells. It was also linked to the Zika virus outbreak in Brazil in 2015, where it caused paralysis in those affected by the syndrome. As of June 29, according to the journal Neurological Sciences, there have been approximately 31 reported cases of Guillain-Barré syndrome caused by COVID-19 worldwide.
Significantly, Dorrill was living off-campus, taking only online courses and, according to his uncle, “told us he was always careful to wear a mask.” Yet, he still contracted the virus, leading to his completely avoidable death. His mother, Susan Dorrill, said that “if it can happen to a super healthy 19-year-old boy who doesn’t smoke, vape or do drugs, it can happen to anyone.”
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Rare neurological disorder, Guillain-Barre Syndrome, linked to COVID-19
The patient in the case report (let’s call him Tom) was 54 and in good health. For two days in May, he felt unwell and was too weak to get out of bed. When his family finally brought him to the hospital, doctors found that he had a fever and signs of a severe infection, or sepsis. He tested positive for SARS-CoV-2, the virus that causes COVID-19 infection. In addition to symptoms of COVID-19, he was also too weak to move his legs.
When a neurologist examined him, Tom was diagnosed with Guillain-Barre Syndrome, an autoimmune disease that causes abnormal sensation and weakness due to delays in sending signals through the nerves. Usually reversible, in severe cases it can cause prolonged paralysis involving breathing muscles, require ventilator support and sometimes leave permanent neurological deficits. Early recognition by expert neurologists is key to proper treatment.
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Rare Disease Database - Guillain-Barré Syndrome
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