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1.
Neurosurg Clin N Am ; 33(3): 297-303, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1914847

ABSTRACT

Most currently available neuromodulation techniques for pain work through an open-loop system. The distance between the epidural space and the target of the stimulation in a dynamic body can change because of physiologic conditions. The closed-loop system in spinal cord neuromodulation consists of an integrated system that records real-time electrophysiological activity in the form of evoked compound action potentials and uses it in a feedback mechanism to adjust stimulus output. Wearables represent newly developed technologies that have gained traction in recent years. Their application in pain management is still developing but promising.


Subject(s)
Spinal Cord Stimulation , Wearable Electronic Devices , Electrophysiology , Humans , Pain Management , Spinal Cord , Spinal Cord Stimulation/methods
2.
EMBO Rep ; 23(6): e54069, 2022 Jun 07.
Article in English | MEDLINE | ID: covidwho-1811581

ABSTRACT

Human coronaviruses have been recently implicated in neurological sequelae by insufficiently understood mechanisms. We here identify an amino acid sequence within the HCoV-OC43 p65-like protein homologous to the evolutionarily conserved motif of myelin basic protein (MBP). Because MBP-derived peptide exposure in the sciatic nerve produces pronociceptive activity in female rodents, we examined whether a synthetic peptide derived from the homologous region of HCoV-OC43 (OC43p) acts by molecular mimicry to promote neuropathic pain. OC43p, but not scrambled peptides, induces mechanical hypersensitivity in rats following intrasciatic injections. Transcriptome analyses of the corresponding spinal cords reveal upregulation of genes and signaling pathways with known nociception-, immune-, and cellular energy-related activities. Affinity capture shows the association of OC43p with an Na+ /K+ -transporting ATPase, providing a potential direct target and mechanistic insight into virus-induced effects on energy homeostasis and the sensory neuraxis. We propose that HCoV-OC43 polypeptides released during infection dysregulate normal nervous system functions through molecular mimicry of MBP, leading to mechanical hypersensitivity. Our findings might provide a new paradigm for virus-induced neuropathic pain.


Subject(s)
Coronavirus OC43, Human , Neuralgia , Amino Acid Sequence , Animals , Coronavirus OC43, Human/physiology , Female , Humans , Peptides , Rats , Spinal Cord
3.
J Korean Med Sci ; 37(7): e52, 2022 Feb 21.
Article in English | MEDLINE | ID: covidwho-1706942

ABSTRACT

Acute transverse myelitis (ATM) has been reported as rare complication of vaccination. Herein, we report 2 cases of ATM after the administration of an mRNA vaccine for coronavirus disease 2019 (COVID-19). The first one is an 81-year-old man who received the BNT162b2 vaccine. He presented with bilateral hand weakness. Spine magnetic resonance imaging (MRI) showed high signal intensity from the C1 to C3 vertebrae. The second is a 23-year-old woman who received the BNT162b2 vaccine and experienced tingling in her legs. Spine MRI showed a high signal intensity lesion at the conus medullaris. These patients were treated with intravenous methylprednisolone and their symptoms improved slightly. Careful follow-up is needed to identify adverse events after the administration of mRNA vaccines for COVID-19.


Subject(s)
/adverse effects , Hand/physiopathology , Leg/physiopathology , Myelitis, Transverse/pathology , Spinal Cord/physiopathology , Vaccination/adverse effects , Aged, 80 and over , COVID-19/immunology , Female , Humans , Magnetic Resonance Imaging , Male , Methylprednisolone/therapeutic use , Myelitis, Transverse/diagnosis , Myelitis, Transverse/drug therapy , SARS-CoV-2/immunology , Spine/diagnostic imaging , Young Adult
4.
5.
Front Immunol ; 12: 783725, 2021.
Article in English | MEDLINE | ID: covidwho-1554650

ABSTRACT

Interferons (IFNs) are cytokines that possess antiviral, antiproliferative, and immunomodulatory actions. IFN-α and IFN-ß are two major family members of type-I IFNs and are used to treat diseases, including hepatitis and multiple sclerosis. Emerging evidence suggests that type-I IFN receptors (IFNARs) are also expressed by microglia, astrocytes, and neurons in the central and peripheral nervous systems. Apart from canonical transcriptional regulations, IFN-α and IFN-ß can rapidly suppress neuronal activity and synaptic transmission via non-genomic regulation, leading to potent analgesia. IFN-γ is the only member of the type-II IFN family and induces central sensitization and microglia activation in persistent pain. We discuss how type-I and type-II IFNs regulate pain and infection via neuro-immune modulations, with special focus on neuroinflammation and neuro-glial interactions. We also highlight distinct roles of type-I IFNs in the peripheral and central nervous system. Insights into IFN signaling in nociceptors and their distinct actions in physiological vs. pathological and acute vs. chronic conditions will improve our treatments of pain after surgeries, traumas, and infections.


Subject(s)
Acute Pain/immunology , Chronic Pain/immunology , Interferon Type I/metabolism , Interferon-gamma/metabolism , /immunology , Acute Pain/pathology , Animals , Chronic Pain/pathology , Disease Models, Animal , Humans , Neuroglia/cytology , Neuroglia/immunology , Neuroglia/pathology , Nociceptors/immunology , Nociceptors/metabolism , Receptors, Interferon/metabolism , Signal Transduction/immunology , Spinal Cord/cytology , Spinal Cord/immunology , Spinal Cord/pathology
6.
Mult Scler Relat Disord ; 58: 103394, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1510133

ABSTRACT

Neuromyelitis optica spectrum disorders (NMOSDs) are uncommon antibody-mediated autoimmune diseases of the central nervous system (CNS), mainly occurring in optic nerves and spinal cord, which can cause visual impairment, paralysis, and occasionally bulbar dysfunction. Such neurological deficits can adversely affect pulmonary functions and increase complicated infection risk. Besides, most NMOSD patients undergo immunosuppressive therapy. All these factors make NMOSD patients the potential high-risk group under the current pandemic of coronavirus disease 2019 (COVID-19). Meanwhile, COVID-19 infection has already been demonstrated as a risk factor for NMOSD relapses. This review discusses the basic immunology of vaccination and common problems, including immunogenicity, safety, and efficacy of vaccination on NMOSD patients. Additionally, we offered vaccination recommendations, health care and treatment advice for NMOSD patients under the background of COVID-19.


Subject(s)
COVID-19 , Neuromyelitis Optica , COVID-19/prevention & control , Humans , Neuromyelitis Optica/complications , SARS-CoV-2 , Spinal Cord , Vaccination/adverse effects
9.
BMJ Case Rep ; 13(9)2020 Sep 21.
Article in English | MEDLINE | ID: covidwho-1304172

ABSTRACT

Clinical manifestations of COVID-19 are known to be variable with growing evidence of nervous system involvement. In this case report, we describe the symptoms of a patient infected with SARS-CoV-2 whose clinical course was complicated with Guillain-Barré syndrome (GBS). We present a case of a 58-year-old woman who was initially diagnosed with COVID-19 pneumonia due to symptoms of fever and cough. Two weeks later, after the resolution of upper respiratory tract symptoms, she developed symmetric ascending quadriparesis and paresthesias. The diagnosis of GBS was made through cerebrospinal fluid analysis and she was successfully treated with intravenous immunoglobulin administration.


Subject(s)
Coronavirus Infections/complications , Guillain-Barre Syndrome/physiopathology , Low Back Pain/physiopathology , Muscle Weakness/physiopathology , Paresthesia/physiopathology , Pneumonia, Viral/complications , Analgesics/therapeutic use , Betacoronavirus , Brain/diagnostic imaging , COVID-19 , Coronavirus Infections/diagnosis , Diagnosis, Differential , Female , Gabapentin/therapeutic use , Guillain-Barre Syndrome/diagnosis , Guillain-Barre Syndrome/etiology , Guillain-Barre Syndrome/therapy , Humans , Immunoglobulins, Intravenous/therapeutic use , Immunologic Factors/therapeutic use , Lumbar Vertebrae/diagnostic imaging , Magnetic Resonance Imaging , Middle Aged , Pandemics , Pneumonia, Viral/diagnosis , Radiculopathy/diagnosis , SARS-CoV-2 , Spinal Cord/diagnostic imaging
10.
J Neuroimaging ; 31(5): 826-848, 2021 09.
Article in English | MEDLINE | ID: covidwho-1262366

ABSTRACT

BACKGROUND AND PURPOSE: We reviewed the literature to evaluate cerebrospinal fluid (CSF) results from patients with coronavirus disease 2019 (COVID-19) who had neurological symptoms and had an MRI that showed (1) central nervous system (CNS) hyperintense lesions not attributed to ischemia and/or (2) leptomeningeal enhancement. We sought to determine if these findings were associated with a positive CSF severe acute respiratory syndrome associated coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR). METHODS: We performed a systematic review of Medline and Embase from December 1, 2019 to November 18, 2020. CSF results were evaluated based on the presence/absence of (1) ≥ 1 CNS hyperintense lesion and (2) leptomeningeal enhancement. RESULTS: In 117 publications, we identified 193 patients with COVID-19 who had an MRI of the CNS and CSF testing. There were 125 (65%) patients with CNS hyperintense lesions. Patients with CNS hyperintense lesions were significantly more likely to have a positive CSF SARS-CoV-2 PCR (10% [9/87] vs. 0% [0/43], p = 0.029). Of 75 patients who had a contrast MRI, there were 20 (27%) patients who had leptomeningeal enhancement. Patients with leptomeningeal enhancement were significantly more likely to have a positive CSF SARS-CoV-2 PCR (25% [4/16] vs. 5% [2/42], p = 0.024). CONCLUSION: The presence of CNS hyperintense lesions or leptomeningeal enhancement on neuroimaging from patients with COVID-19 is associated with increased likelihood of a positive CSF SARS-CoV-2 PCR. However, a positive CSF SARS-CoV-2 PCR is uncommon in patients with these neuroimaging findings, suggesting they are often related to other etiologies, such as inflammation, hypoxia, or ischemia.


Subject(s)
COVID-19 , Nervous System Diseases , Brain , Humans , SARS-CoV-2 , Spinal Cord
11.
Front Immunol ; 12: 653786, 2021.
Article in English | MEDLINE | ID: covidwho-1226977

ABSTRACT

Introduction: Although acute transverse myelitis (ATM) is a rare neurological condition (1.34-4.6 cases per million/year) COVID-19-associated ATM cases have occurred during the pandemic. Case-finding methods: We report a patient from Panama with SARS-CoV-2 infection complicated by ATM and present a comprehensive clinical review of 43 patients with COVID-19-associated ATM from 21 countries published from March 2020 to January 2021. In addition, 3 cases of ATM were reported as serious adverse events during the clinical trials of the COVID-19 vaccine ChAdOx1 nCoV-19 (AZD1222). Results: All patients had typical features of ATM with acute onset of paralysis, sensory level and sphincter deficits due to spinal cord lesions demonstrated by imaging. There were 23 males (53%) and 20 females (47%) ranging from ages 21- to 73- years-old (mean age, 49 years), with two peaks at 29 and 58 years, excluding 3 pediatric cases. The main clinical manifestations were quadriplegia (58%) and paraplegia (42%). MRI reports were available in 40 patients; localized ATM lesions affected ≤3 cord segments (12 cases, 30%) at cervical (5 cases) and thoracic cord levels (7 cases); 28 cases (70%) had longitudinally-extensive ATM (LEATM) involving ≥4 spinal cord segments (cervicothoracic in 18 cases and thoracolumbar-sacral in 10 patients). Acute disseminated encephalomyelitis (ADEM) occurred in 8 patients, mainly women (67%) ranging from 27- to 64-years-old. Three ATM patients also had blindness from myeloneuritis optica (MNO) and two more also had acute motor axonal neuropathy (AMAN). Conclusions: We found ATM to be an unexpectedly frequent neurological complication of COVID-19. Most cases (68%) had a latency of 10 days to 6 weeks that may indicate post-infectious neurological complications mediated by the host's response to the virus. In 32% a brief latency (15 hours to 5 days) suggested a direct neurotropic effect of SARS-CoV-2. The occurrence of 3 reported ATM adverse effects among 11,636 participants in the AZD1222 vaccine trials is extremely high considering a worldwide incidence of 0.5/million COVID-19-associated ATM cases found in this report. The pathogenesis of ATM remains unknown, but it is conceivable that SARS-CoV-2 antigens -perhaps also present in the AZD1222 COVID-19 vaccine or its chimpanzee adenovirus adjuvant- may induce immune mechanisms leading to the myelitis.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19/complications , Myelitis, Transverse/complications , SARS-CoV-2/pathogenicity , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Myelitis, Transverse/diagnosis , Myelitis, Transverse/pathology , Myelitis, Transverse/physiopathology , Nervous System Diseases/complications , Nervous System Diseases/diagnosis , Nervous System Diseases/pathology , Nervous System Diseases/physiopathology , SARS-CoV-2/immunology , SARS-CoV-2/physiology , Spinal Cord/diagnostic imaging , Spinal Cord/pathology , Spinal Cord/physiopathology , Viral Tropism , Young Adult
13.
BMJ Case Rep ; 13(12)2020 Dec 17.
Article in English | MEDLINE | ID: covidwho-1177537

ABSTRACT

Radiation-induced spinal glioblastoma is an extremely rare disease with only four previously published reports in the literature. We report the fifth case, a 69-year-old woman who previously underwent treatment with brachytherapy for cervical cancer, and thereafter presented with neurologic deficits from a conus medullaris tumour. Biopsy and histopathology confirm glioblastoma, not otherwise specified. Treatment of spinal glioblastoma consists of surgery, either biopsy or excision and chemoradiation. However, results are still unsatisfactory and prognosis remains poor.


Subject(s)
Brachytherapy/adverse effects , Glioblastoma/diagnosis , Neoplasms, Radiation-Induced/diagnosis , Spinal Cord Neoplasms/diagnosis , Uterine Cervical Neoplasms/radiotherapy , Aged , Biopsy , Cytoreduction Surgical Procedures , Female , Glioblastoma/etiology , Glioblastoma/pathology , Glioblastoma/surgery , Humans , Laminectomy , Magnetic Resonance Imaging , Neoplasms, Radiation-Induced/etiology , Neoplasms, Radiation-Induced/pathology , Neoplasms, Radiation-Induced/surgery , Spinal Cord/diagnostic imaging , Spinal Cord/pathology , Spinal Cord/radiation effects , Spinal Cord/surgery , Spinal Cord Neoplasms/etiology , Spinal Cord Neoplasms/pathology , Spinal Cord Neoplasms/surgery
14.
PLoS One ; 16(4): e0249095, 2021.
Article in English | MEDLINE | ID: covidwho-1167104

ABSTRACT

BACKGROUND: Neurodegenerative diseases are sporadic hereditary conditions characterized by progressive dysfunction of the nervous system. Among the symptoms, vestibulopathy is one of the causes of discomfort and a decrease in quality of life. Hereditary spastic paraplegia is a heterogeneous group of hereditary degenerative diseases involving the disorder of a single gene and is characterized by the progressive retrograde degeneration of fibers in the spinal cord. OBJECTIVE: To determine the benefits of vestibular rehabilitation involving virtual reality by comparing pre intervention and post intervention assessments in individuals with hereditary spastic paraplegia. METHODS: In this randomized controlled clinical trial from the Rebec platform RBR-3jmx67 in which allocation concealment was performed and the evaluators be blinded will be included. The participants will include 40 patients diagnosed with hereditary spastic paraplegia. The interventions will include vestibular rehabilitation with virtual reality using the Wii® console, Wii-Remote and Wii Balance Board (Nintendo), and the studies will include pre- and post intervention assessments. Group I will include twenty volunteers who performed balance games. Group II will include twenty volunteers who performed balance games and muscle strength games. The games lasted from 30 minutes to an hour, and the sessions were performed twice a week for 10 weeks (total: 20 sessions). RESULTS: This study provides a definitive assessment of the effectiveness of a virtual reality vestibular rehabilitation program in halting the progression of hereditary spastic paraplegia, and this treatment can be personalized and affordable. CONCLUSION: The study will determine whether a vestibular rehabilitation program with the Nintendo Wii® involving virtual reality can reduce the progressive effect of hereditary spastic paraplegia and serve as an alternative treatment option that is accessible and inexpensive. Rebec platform trial: RBR-3JMX67.


Subject(s)
Exercise Therapy , Postural Balance/genetics , Spastic Paraplegia, Hereditary/rehabilitation , Spinal Cord/pathology , Adolescent , Adult , Brazil , Cognitive Dysfunction/physiopathology , Cognitive Dysfunction/rehabilitation , Female , Games, Recreational , Humans , Male , Middle Aged , Muscle Strength/physiology , Pain/physiopathology , Pain/prevention & control , Quality of Life , Spastic Paraplegia, Hereditary/genetics , Spastic Paraplegia, Hereditary/physiopathology , Treatment Outcome , Virtual Reality , Young Adult
15.
Mult Scler Relat Disord ; 51: 102917, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1142159

ABSTRACT

BACKGROUND: Spinal cord complications associated with coronavirus infectious disease of 2019 (COVID-19) are being widely reported. The purpose of this systematic review was to summarize so far available pieces of evidence documenting de novo novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) mediated spinal cord demyelinating diseases. Indeed, the spinal demyelinating disorders that have been reported in those patients who have suffered from COVID-19 rather than on the people already living with diagnosed or undiagnosed primary demyelinating disorders. METHODS: We used the existing PRISMA consensus statement. Data were collected from PubMed, NIH Litcovid, EMBASE and Cochrane library databases, as well as Pre-print servers (medRxiv, bioRxiv, and pre-preints.org), until September 10, 2020, using pre-specified searching strategies. RESULTS: The 21 selected articles were all case reports and included 11 (52%) men and 10 (48%) women. The mean age was of 46.7 ±â€¯18.0. The neurological manifestations included weakness, sensory deficit, autonomic dysfunction and ataxia. In most cases, elevated cerebrospinal fluid protein as well as lymphocytic pleocytosis were found. SARS-CoV-2 was detected in five (24%) patients, meanwhile in 13 (62%) patients, the testing was negative. Testing was not performed in two cases and, in one, data were unavailable. Nearly half of the cases (N = 9) were associated with isolated long extensive transverse myelitis (LETM), whereas a combination of both LETM and patchy involvement was found in two. Only five patients had isolated short segment involvement and two patchy involvement. Furthermore, concomitant demyelination of both brain and spine was reported in six patients. Concerning the prognosis, most of the patients improved and the mortality rate was low (N = 2, <10%). CONCLUSION: Spinal cord demyelination should be added to the plethora of immune mediated neurologic complications associated with COVID-19.


Subject(s)
COVID-19 , Communicable Diseases , Nervous System Diseases , Female , Humans , Male , SARS-CoV-2 , Spinal Cord
16.
Neuroepidemiology ; 55(2): 109-118, 2021.
Article in English | MEDLINE | ID: covidwho-1102234

ABSTRACT

BACKGROUND: COVID-19 can be accompanied by acute neurological complications of both central and peripheral nervous systems (CNS and PNS). In this study, we estimate the frequency of such complications among hospital inpatients with COVID-19 in Assiut and Aswan university hospitals. MATERIALS AND METHODS: We screened all patients with suspected COVID-19 admitted from 1 June to 10 August 2020 to the university hospitals of Assiut and Aswan in Upper Egypt. Clinical and laboratory tests, CT/MRI of the chest and brain, and neurophysiology study were performed for each patient if indicated. RESULTS: 439 patients had confirmed/probable COVID-19; neurological manifestations occurred in 222. Of these, 117 had acute neurological disease and the remainder had nonspecific neuropsychiatric symptoms such as headache, vertigo, and depression. The CNS was affected in 75 patients: 55 had stroke and the others had convulsions (5), encephalitis (6), hypoxic encephalopathy (4), cord myelopathy (2), relapse of multiple sclerosis (2), and meningoencephalitis (1). The PNS was affected in 42 patients: the majority had anosmia and ageusia (31) and the others had Guillain-Barré syndrome (4), peripheral neuropathy (3), myasthenia gravis (MG, 2), or myositis (2). Fever, respiratory symptoms, and headache were the most common general symptoms. Hypertension, diabetes mellitus, and ischemic heart disease were the most common comorbidities in patients with CNS affection. CONCLUSION: In COVID-19, both the CNS and PNS are affected. Stroke was the most common complication for CNS, and anosmia and/or ageusia were common for PNS diseases. However, there were 6 cases of encephalitis, 2 cases of spinal cord myelopathy, 2 cases of MG, and 2 cases of myositis.


Subject(s)
Anosmia/physiopathology , COVID-19/physiopathology , Central Nervous System Diseases/physiopathology , Peripheral Nervous System Diseases/physiopathology , Stroke/physiopathology , Adult , Aged , Anosmia/epidemiology , Brain/diagnostic imaging , COVID-19/diagnosis , COVID-19/epidemiology , Central Nervous System Diseases/diagnosis , Central Nervous System Diseases/epidemiology , Disease Progression , Egypt/epidemiology , Encephalitis/epidemiology , Encephalitis/physiopathology , Female , Guillain-Barre Syndrome/epidemiology , Guillain-Barre Syndrome/physiopathology , Hospitals, University , Humans , Hypoxia, Brain/epidemiology , Hypoxia, Brain/physiopathology , Lung/diagnostic imaging , Magnetic Resonance Imaging , Male , Middle Aged , Multiple Sclerosis, Relapsing-Remitting/epidemiology , Multiple Sclerosis, Relapsing-Remitting/physiopathology , Myasthenia Gravis/epidemiology , Myasthenia Gravis/physiopathology , Myositis/epidemiology , Myositis/physiopathology , Peripheral Nervous System Diseases/diagnosis , Peripheral Nervous System Diseases/epidemiology , SARS-CoV-2 , Seizures/epidemiology , Seizures/physiopathology , Spinal Cord/diagnostic imaging , Spinal Cord Diseases/epidemiology , Spinal Cord Diseases/physiopathology , Stroke/diagnosis , Stroke/epidemiology , Tomography, X-Ray Computed
17.
J Neuroimmunol ; 353: 577523, 2021 04 15.
Article in English | MEDLINE | ID: covidwho-1091757

ABSTRACT

OBJECTIVE: To report a unique case and literature review of post COVID-19 associated transverse myelitis and dysautonomia with abnormal MRI and CSF findings. BACKGROUND: Coronavirus disease have been reported to be associated with several neurological manifestations such as stroke, Guillain-Barré syndrome, meningoencephalitis amongst others. There are only few reported cases of transverse myelitis with the novel coronavirus (n-CoV-2) and only one reported case identifying dysautonomia in COVID-19 patient. Here, we identify a COVID-19 patient diagnosed with acute transverse myelitis in addition to dysautonomia following with complete resolution of symptoms. METHOD: A retrospective chart review of a patient diagnosed with post SARS-CoV-2 infection acute transverse myelitis and dysautonomia, and a review of literature of all the reported cases of transverse myelitis and COVID-19, from December 1st, 2019 till December 25th, 2020, was performed. CONCLUSION: To our knowledge, this is the first reported case of transverse myelitis and dysautonomia in a patient with SARS-CoV-2 infection, who responded to intravenous methyl prednisone and bromocriptine. Follow-up imaging of the spine showed complete resolution of the lesion. Further studies would be recommended to identify the underlying correlation between COVID-19 and transverse myelitis.


Subject(s)
COVID-19/complications , Myelitis, Transverse/virology , Primary Dysautonomias/virology , Spinal Cord/pathology , Adult , Anti-Inflammatory Agents/therapeutic use , Bromocriptine/therapeutic use , COVID-19/pathology , Dopamine Agonists/therapeutic use , Humans , Male , Methylprednisolone/therapeutic use , Myelitis, Transverse/drug therapy , Myelitis, Transverse/pathology , SARS-CoV-2
18.
Brain Behav Immun ; 91: 740-755, 2021 01.
Article in English | MEDLINE | ID: covidwho-1064860

ABSTRACT

Central nervous system (CNS) innate immunity plays essential roles in infections, neurodegenerative diseases, and brain or spinal cord injuries. Astrocytes and microglia are the principal cells that mediate innate immunity in the CNS. Pattern recognition receptors (PRRs), expressed by astrocytes and microglia, sense pathogen-derived or endogenous ligands released by damaged cells and initiate the innate immune response. Toll-like receptors (TLRs) are a well-characterized family of PRRs. The contribution of microglial TLR signaling to CNS pathology has been extensively investigated. Even though astrocytes assume a wide variety of key functions, information about the role of astroglial TLRs in CNS disease and injuries is limited. Because astrocytes display heterogeneity and exhibit phenotypic plasticity depending on the effectors present in the local milieu, they can exert both detrimental and beneficial effects. TLRs are modulators of these paradoxical astroglial properties. The goal of the current review is to highlight the essential roles played by astroglial TLRs in CNS infections, injuries and diseases. We discuss the contribution of astroglial TLRs to host defense as well as the dissemination of viral and bacterial infections in the CNS. We examine the link between astroglial TLRs and the pathogenesis of neurodegenerative diseases and present evidence showing the pivotal influence of astroglial TLR signaling on sterile inflammation in CNS injury. Finally, we define the research questions and areas that warrant further investigations in the context of astrocytes, TLRs, and CNS dysfunction.


Subject(s)
Astrocytes/metabolism , Neurodegenerative Diseases/physiopathology , Toll-Like Receptors/physiology , Animals , Astrocytes/physiology , Brain/metabolism , Central Nervous System/immunology , Central Nervous System/metabolism , Central Nervous System Diseases/immunology , Central Nervous System Infections/pathology , Encephalitis/immunology , Humans , Immunity, Innate/physiology , Microglia/metabolism , Neurodegenerative Diseases/metabolism , Neurons/metabolism , Receptors, Pattern Recognition/immunology , Signal Transduction , Spinal Cord/pathology , Spinal Cord Injuries/pathology , Toll-Like Receptors/metabolism
19.
Ann Clin Transl Neurol ; 8(2): 385-394, 2021 02.
Article in English | MEDLINE | ID: covidwho-995827

ABSTRACT

OBJECTIVE: Pivotal trial have shown that patients with multiple sclerosis (MS) receiving ocrelizumab had better outcomes. However, data on ocrelizumab in clinical practice are limited. The aim of this study was to evaluate the preliminary safety profile and effectiveness of ocrelizumab treatment for multiple sclerosis (MS) in a real-world clinical setting. METHODS: We conducted a retrospective study including consecutive patients from nine public hospitals in south-eastern Spain who received ocrelizumab after it was approved. RESULTS: A total of 228 MS patients were included (144 with relapsing-remitting MS [RRMS], 25 secondary progressive MS [SPMS], and 59 primary progressive MS [PPMS]). Median follow-up period was 12 months (range, 1-32). No evidence of disease activity (NEDA) status at year 1 was achieved in 91.2% of the relapsing MS (RMS) population, while disability progression was detected in 37.5% of the PPMS patients (median follow-up period, 19 months). The most common adverse events reported were infusion-related reactions and infections, with the most common infections being urinary tract infections followed by upper respiratory infections and COVID-19. INTERPRETATION: The preliminary results in our real-world setting show that ocrelizumab presented excellent results in suppressing disease activity with a favorable and consistent safety profile.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Immunologic Factors/therapeutic use , Multiple Sclerosis, Chronic Progressive/drug therapy , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Adult , Brain/diagnostic imaging , Disease Progression , Female , Humans , Injection Site Reaction , Magnetic Resonance Imaging , Male , Middle Aged , Multiple Sclerosis, Chronic Progressive/diagnostic imaging , Multiple Sclerosis, Chronic Progressive/physiopathology , Multiple Sclerosis, Relapsing-Remitting/diagnostic imaging , Multiple Sclerosis, Relapsing-Remitting/physiopathology , Retrospective Studies , Spain , Spinal Cord/diagnostic imaging , Treatment Outcome
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