Showing papers in "Frontiers in Neurology in 2020"
TL;DR: Clinical and radiological differences between AQP4-antibody and MOG-anibody associated diseases have led to interest in the revisions of NMOSD definition and expanded stratification based on detection of a specific autoantibODY biomarker.
Abstract: Neuromyelitis optica spectrum disorder (NMOSD) is an uncommon inflammatory disease of the central nervous system, manifesting clinically as optic neuritis, myelitis, and certain brain and brainstem syndromes Cases clinically diagnosed as NMOSD may include aquaporin 4 (AQP4)-antibody-seropositive autoimmune astrocytopathic disease, myelin oligodendrocyte glycoprotein (MOG)-antibody-seropositive inflammatory demyelinating disease, and double-seronegative disease AQP4-antibody disease has a high female-to-male ratio (up to 9:1), and its mean age at onset of ~40 years is later than that seen in multiple sclerosis For MOG-antibody disease, its gender ratio is closer to 1:1, and it is more common in children than in adults Its clinical phenotypes differ but overlap with those of AQP4-antibody disease and include acute disseminated encephalomyelitis, brainstem and cerebral cortical encephalitis, as well as optic neuritis and myelitis Double-seronegative disease requires further research and clarification Population-based studies over the past two decades report the prevalence and incidence of NMOSD in different populations worldwide One relevant finding is the varying prevalence observed in different racial groups Consistently, the prevalence of NMOSD among Whites is ~1/100,000 population, with an annual incidence of <1/million population Among East Asians, the prevalence is higher, at ~35/100,000 population, while the prevalence in Blacks may be up to 10/100,000 population For MOG-antibody disease, hospital-based studies largely do not observe any significant racial preponderance so far This disorder comprises a significant proportion of NMOSD cases that are AQP4-antibody-seronegative A recent Dutch nationwide study reported the annual incidence of MOG-antibody disease as 16/million population (adult: 13/million, children: 31/million) Clinical and radiological differences between AQP4-antibody and MOG-antibody associated diseases have led to interest in the revisions of NMOSD definition and expanded stratification based on detection of a specific autoantibody biomarker More population-based studies in different geographical regions and racial groups will be useful to further inform the prevalence and incidence of NMOSD and their antibody-specific subgroups Accessibility to AQP4-antibody and MOG-antibody testing, which is limited in many centers, is a challenge to overcome Environmental and genetic studies will be useful accompaniments to identify other potential pathogenetic factors and specific biomarkers in NMOSD
180 citations
TL;DR: The neuropathology of AD was reviewed and new insights in the pathogenesis of AD were discussed, including gamma oscillations, prion transmission, cerebral vasoconstriction, growth hormone secretagogue receptor 1α-mediated mechanism, and infection.
Abstract: Alzheimer's disease (AD), a common neurodegenerative disease in the elderly and the most prevalent cause of dementia, is characterized by progressive cognitive impairment. The prevalence of AD continues to increase worldwide, becoming a great healthcare challenge of the twenty-first century. In the more than 110 years since AD was discovered, many related pathogenic mechanisms have been proposed, and the most recognized hypotheses are the amyloid and tau hypotheses. However, almost all clinical trials targeting these mechanisms have not identified any effective methods to treat AD. Scientists are gradually moving away from the simple assumption, as proposed in the original amyloid hypothesis, to new theories of pathogenesis, including gamma oscillations, prion transmission, cerebral vasoconstriction, growth hormone secretagogue receptor 1α (GHSR1α)-mediated mechanism, and infection. To place these findings in context, we first reviewed the neuropathology of AD and further discussed new insights in the pathogenesis of AD.
163 citations
TL;DR: The different pathological and physiological repair mechanisms involved in BBB permeability through the different stages of ischemic stroke and their role in the development of HT and stroke recovery are addressed.
Abstract: The blood-brain barrier (BBB) is a dynamic interface responsible for maintaining the central nervous system homeostasis. Its unique characteristics allow protecting the brain from unwanted compounds, but its impairment is involved in a vast number of pathological conditions. Disruption of the BBB and increase in its permeability are key in the development of several neurological diseases and have been extensively studied in stroke. Ischemic stroke is the most prevalent type of stroke and is characterized by a myriad of pathological events triggered by an arterial occlusion that can eventually lead to fatal outcomes such as hemorrhagic transformation (HT). BBB permeability seems to follow a multiphasic pattern throughout the different stroke stages that have been associated with distinct biological substrates. In the hyperacute stage, sudden hypoxia damages the BBB, leading to cytotoxic edema and increased permeability; in the acute stage, the neuroinflammatory response aggravates the BBB injury, leading to higher permeability and a consequent risk of HT that can be motivated by reperfusion therapy; in the subacute stage (1-3 weeks), repair mechanisms take place, especially neoangiogenesis. Immature vessels show leaky BBB, but this permeability has been associated with improved clinical recovery. In the chronic stage (>6 weeks), an increase of BBB restoration factors leads the barrier to start decreasing its permeability. Nonetheless, permeability will persist to some degree several weeks after injury. Understanding the mechanisms behind BBB dysregulation and HT pathophysiology could potentially help guide acute stroke care decisions and the development of new therapeutic targets; however, effective translation into clinical practice is still lacking. In this review, we will address the different pathological and physiological repair mechanisms involved in BBB permeability through the different stages of ischemic stroke and their role in the development of HT and stroke recovery.
150 citations
TL;DR: The identification of appropriate, characteristic image features as well as the generation of predictive or prognostic mathematical models is summarized under the term radiomics, which summarizes the current status of radiomics in patients with brain metastases.
Abstract: Although a variety of imaging modalities are used or currently being investigated for patients with brain tumors including brain metastases, clinical image interpretation to date uses only a fraction of the underlying complex, high-dimensional digital information from routinely acquired imaging data. The growing availability of high-performance computing allows the extraction of quantitative imaging features from medical images that are usually beyond human perception. Using machine learning techniques and advanced statistical methods, subsets of such imaging features are used to generate mathematical models that represent characteristic signatures related to the underlying tumor biology and might be helpful for the assessment of prognosis or treatment response, or the identification of molecular markers. The identification of appropriate, characteristic image features as well as the generation of predictive or prognostic mathematical models is summarized under the term radiomics. This review summarizes the current status of radiomics in patients with brain metastases.
148 citations
TL;DR: The neurological manifestations associated with COVID-19 such as Encephalitis, Meningitis, acute cerebrovascular disease, and Guillain Barré Syndrome are of great concern and there is a need to diagnose these manifestations at the earliest to limit long term sequelae.
Abstract: Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been associated with many neurological symptoms but there is a little evidence-based published material on the neurological manifestations of COVID-19. The purpose of this article is to review the spectrum of the various neurological manifestations and underlying associated pathophysiology in COVID-19 patients. Method: We conducted a review of the various case reports and retrospective clinical studies published on the neurological manifestations, associated literature, and related pathophysiology of COVID-19 using PUBMED and subsequent proceedings. A total of 118 articles were thoroughly reviewed in order to highlight the plausible spectrum of neurological manifestations of COVID 19. Every article was either based on descriptive analysis, clinical scenarios, correspondence, and editorials emphasizing the neurological manifestations either directly or indirectly. We then tried to highlight the significant plausible manifestations and complications that could be related to the pandemic. With little known about the dynamics and the presentation spectrum of the virus apart from the respiratory symptoms, this area needs further consideration. Conclusion: The neurological manifestations associated with COVID-19 such as Encephalitis, Meningitis, acute cerebrovascular disease, and Guillain Barre Syndrome (GBS) are of great concern. But in the presence of life-threatening abnormal vitals in severely ill COVID-19 patients, these are not usually underscored. There is a need to diagnose these manifestations at the earliest to limit long term sequelae. Much research is needed to explore the role of SARS-CoV-2 in causing these neurological manifestations by isolating it either from cerebrospinal fluid or brain tissues of the deceased on autopsy. We also recommend exploring the risk factors that lead to the development of these neurological manifestations.
148 citations
TL;DR: The evidence on the neurological and musculoskeletal symptoms of COVID-19 may help with early diagnosis, prevention of disease spread, and treatment planning, and clinicians need to be vigilant in the diagnosis and treatment of patients.
Abstract: Importance: Some of the symptoms of COVID-19 are fever, cough and respiratory difficulty However, the mechanism of the disease including some of the symptoms such as the neurological and musculoskeletal symptoms is still poorly understood Objective: The aim of this review is to summarize the evidence on the neurological and musculoskeletal symptoms of the disease This may help with early diagnosis, prevention of the disease spread and plan of treatment Data sources: MEDLINE, EMBASE, Web of Science and Google scholar (first 100 hits) were searched until April 17th, 2020 The key search terms used were “coronavirus” and “signs and symptoms”Only studies written in English were included Study selection: The selection was performed using EndNote and Rayyan softwares by two independent reviewers Any disagreement was resolved by consensus meeting or by a third reviewer Data extraction and synthesis: PRISMA guideline was used for abstracting data and assessing the quality of the studies These were carried out by two and three independent reviewers respectively Any disagreement was resolved by consensus meeting or by a third reviewer The data was analyzed using qualitative synthesis and pooled using a random-effect model Main Outcome(s) and Measure(s): The outcomes in the study include country, study design, participant details (sex, age, sample size); and neurological and musculoskeletal features Result: Sixty studies (n=11, 069) were included in the review; and 51 studies were used in the meta-analysis The median or mean age ranges from 24 to 95 years The prevalence of neurological and musculoskeletal manifestations was 35% for smell impairment (95% CI 0-94%; I2 9963%), 33% for taste impairment (95% CI 0-91%; I2 99 58%), 19% for myalgia (95% CI 16-23; I2 95%), 12% for headache (95% CI 9-15; I2 9312%), 10% for back pain (95% CI 1-23%; I2 8020%), 10% for dizziness(95% CI 3-19%; I2 8674%), 3% for acute cerebrovascular disease (95% CI 1-5%; I2 0%) and 2% for impaired consciousness (95% CI 1-2%; I2 0%) Conclusion and Relevance: Patients with COVID-19 present with neurological and musculoskeletal symptoms Therefore, clinicians need to be vigilant in the diagnosis and treatment of these patients
116 citations
TL;DR: Doctors should be aware of the presence of neurologic signs and symptoms as a chief complaint of COVID-19, in order to improve management and prevent a worsening outcome of the patients, according to the Oxford Center for Evidence-Based Medicine guidelines.
Abstract: Importance: Coronavirus disease 2019 (COVID-19) is a newly emerging infectious disease that has caused a global pandemic. The presenting symptoms are mainly respiratory symptom, yet studies have reported nervous system involvement in the disease. A systematic review and meta-analysis of these studies are required to understanding the neurologic characteristic of the disease and help physicians with early diagnosis and management. Objective: To conduct a systematic review and meta-analysis on the neurologic characteristics in patients with COVID-19. Evidence Review: Authors conducted a literature search through PubMed from January 1st, 2020 to April 8th, 2020. Furthermore, the authors added additional sources by reviewing related references. Studies presenting the neurologic features of COVID-19 patients in their data were included. Case reports and case series were also included in this review. The quality of the studies was assessed based on the Oxford Center for Evidence-Based Medicine guidelines. Selected studies were included in the meta-analysis of proportion and the heterogeneity test. Finding: From 280 identified studies, 33 were eligible, with 7,559 participants included. Most of the included studies were from China (29 [88%]). Muscle injury or myalgia was the most common (19.2%, 95%CI 15.4-23.2%) neurologic symptom of COVID-19, followed by headache (10.9%, 95%CI 8.62-13.51%); dizziness (8.7%, 95%CI 5.02-13.43%); nausea with or without vomiting (4.6%, 95%CI 3.17-6.27%); concurrent cerebrovascular disease (4.4%, 95%CI 1.92-7.91%); and impaired consciousness (3.8%, 95%CI 0.16-12.04%). Underlying cerebrovascular disease was found in 8.5% (95%CI 4.5-13.5%) of the studies. Conclusion: Neurologic findings vary from non-specific to specific symptoms in COVID-19 patients. Some severe symptoms or diseases can present in the later stage of the disease. Physicians should be aware of the presence of neurologic signs and symptoms as a chief complaint of COVID-19, in order to improve management and prevent a worsening outcome of the patients.
102 citations
TL;DR: During the current COVID-19 pandemic, a significant percentage of people with epilepsy (PwE) experienced difficulties in follow-up and a seizure number increase, in particular those chronically taking more ASMs and with poor sleep quality.
Abstract: Objective: In early 2020, Italy struggled with an unprecedented health emergency related to the COVID-19 pandemic. Medical care of chronic neurological diseases, such as epilepsy, is being sorely neglected. In this national survey, we aimed at understanding the impact of COVID-19 lockdown on the care of people with epilepsy (PwE) and identifying PwE risk factors for seizure worsening to direct telemedicine efforts. Methods: We administered a 48-items online survey (published on April 11, 2020) including socio-demographic, epilepsy-related, and psychometric variables (BDI-II for depression, GAD-7 for anxiety, and PSQI for sleep) to PwE and people without epilepsy (PwoE). Regression analysis identified predictors of seizure worsening. Results: We collected responses from 456 PwE (344 females) and 472 PwoE (347 females). Outpatient examinations of PwE were postponed in 95% of cases. One-third of PwE complained of issues with epilepsy management, but only 71% of them reached the treating physician and solved their problems. PwE had worse depressive and anxiety symptoms (higher BDI-II and GAD-7 scores; p < 0.001) than PwoE. Sleep quality was equally compromised in both groups (47 and 42%). Sixty-seven PwE (18%) reported seizure worsening, which was best explained by the number of anti-seizure medications (ASM) of chronic therapy and the severity of sleep disorder. Conclusions: During the current COVID-19 pandemic, a significant percentage of PwE experienced difficulties in follow-up and a seizure number increase, in particular those chronically taking more ASMs and with poor sleep quality. This dramatic experience outlines the urgent need for validation and implementation of telemedicine services for epileptic patients in order to provide regular follow-up.
99 citations
TL;DR: It is asserted that the most important and urgent interventions concern enhanced education, more effective technology transfer, and increased academic opportunities for physiotherapists, occupational therapists, and kinesiologists.
Abstract: This article addresses the potential clinical value of techniques based on surface electromyography (sEMG) in rehabilitation medicine with specific focus on neurorehabilitation. Applications in exercise and sport physiopathology, in movement analysis, in ergonomics and occupational medicine, and in a number of related fields are also considered. The contrast between the extensive scientific literature in these fields and the limited clinical applications is discussed. The “barriers” between research findings and their application are very broad, and are longstanding, cultural, educational and technical. Cultural barriers relate to the general acceptance and use of the concept of objective measurement in a clinical settings and its role in promoting Evidence Based Medicine. Wide differences between countries exist in appropriate training in the use of such quantitative measurements in general, and in electrical measurements in particular. These differences are manifest in training programs, in degrees granted, and in academic/research career opportunities Educational barriers are related to the background in mathematics and physics for rehabilitation clinicians, leading to insufficient basic concepts of signal interpretation, as well as to the lack of a common language with rehabilitation engineers. Technical barriers are being overcome progressively, but progress is still impacted by the lack of user-friendly equipment, insufficient market demand, gadget-like devices, relatively high equipment price and a pervasive lack of interest by manufacturers. Despite the recommendations provided by the 20-year old EU project on “Surface EMG for Non Invasive Assessment of Muscles (SENIAM)”, real international standards are still missing and there is minimal international pressure for developing and applying such standards. The need for change in training and teaching is increasingly felt in the academic world, but is much less evident in the health delivery system and clinical environments. The rapid technological progress in the fields of sensor and measurement technology (including sEMG), assistive devices, and robotic rehabilitation, is not conditioned, and sometime not even perceived, by the potential clinical users. Our assertion is that the most important and urgent interventions concern enhanced education, more effective technology transfer, and increased academic opportunities for physiotherapists and kinesiologists.
94 citations
TL;DR: The gut microbiota of patients with PD-MCI was significantly altered, particularly manifesting in enriched genera from Porphyromonadaceae family and decreased the abundance of genera Blautia and Ruminococcus.
Abstract: Background and Aim: Gut bacteria play an important role in the pathogenesis of Parkinson's disease (PD). However, the alteration of fecal microbiota in PD with cognitive impairment remains unexplored. This study aimed to explore whether the gut microbiota of patients with PD having mild cognitive impairment (PD-MCI) were different from those with PD having normal cognition (PD-NC) and from healthy controls (HC). Also, the study probed the association between altered gut microbiota and cognitive ability in patients with PD. Methods: The fecal bacteria composition and short-chain fatty acids of 13 patients with PD-MCI, 14 patients with PD-NC, and 13 healthy spouses were analyzed using 16S ribosomal RNA sequencing and gas chromatography-mass spectrometry. Results: Compared with HC, the fecal microbial diversities increased in patients with PD-MCI and PD-NC. After adjusting the influence of age, sex, body mass index, education, and constipation using the statistical method, the relative abundances of two families (Rikenellaceae and Ruminococcaceae) and four genera (Alistipes, Barnesiella, Butyricimonas, and Odoribacter) were found to be higher in the feces of the PD-MCI group compared with the other two groups. Moreover, the abundance of genus Blautia and Ruminococcus decreased obviously in the PD-MCI group compared with the PD-NC group. Further, the abundance of genera Butyricimonas, Barnesiella, Alistipes, Odoribacter, and Ruminococcus negatively correlated with cognition ability. Conclusion: Compared with HC and patients with PD-NC, the gut microbiota of patients with PD-MCI was significantly altered, particularly manifesting in enriched genera from Porphyromonadaceae family and decreased the abundance of genera Blautia and Ruminococcus.
91 citations
TL;DR: This work will briefly review current evidence-based recommendations on the efficacy of cognitive rehabilitation and offer a perspective on the role of tele- and virtual rehabilitation to achieve adequate cognitive stimulation in the era of social distancing related to COVID-19 pandemic.
Abstract: The current COVID-19 pandemic presents unprecedented new challenges to public health and medical care delivery. To control viral transmission, social distancing measures have been implemented all over the world, interrupting the access to routine medical care for many individuals with neurological diseases. Cognitive disorders are common in many neurological conditions, e.g., stroke, traumatic brain injury, Alzheimer's disease, and other types of dementia, Parkinson's disease and parkinsonian syndromes, and multiple sclerosis, and should be addressed by cognitive rehabilitation interventions. To be effective, cognitive rehabilitation programs must be intensive and prolonged over time; however, the current virus containment measures are hampering their implementation. Moreover, the reduced access to cognitive rehabilitation might worsen the relationship between the patient and the healthcare professional. Urgent measures to address issues connected to COVID-19 pandemic are, therefore, needed. Remote communication technologies are increasingly regarded as potential effective options to support health care interventions, including neurorehabilitation and cognitive rehabilitation. Among them, telemedicine, virtual reality, augmented reality, and serious games could be in the forefront of these efforts. We will briefly review current evidence-based recommendations on the efficacy of cognitive rehabilitation and offer a perspective on the role of tele- and virtual rehabilitation to achieve adequate cognitive stimulation in the era of social distancing related to COVID-19 pandemic. In particular, we will discuss issues related to their diffusion and propose a roadmap to address them. Methodological and technological improvements might lead to a paradigm shift to promote the delivery of cognitive rehabilitation to people with reduced mobility and in remote regions.
TL;DR: The role of microglia and the activation of the inflammasome in the innate immune response to AD is reviewed and several recent reports indicate that the assembly of the multi-protein complex known as the NOD, LRR, and pyrin-domain containing 3 (Nlrp3) inflammaome by microglian results in apoptosis spec-like protein containing a CARD (Asc) spec formation, thus amplifying Aβ-associated pathology.
Abstract: Alzheimer's disease (AD) is the most prevalent form of late-onset dementia. AD affects the health of millions of people in the United States and worldwide. Currently, there are no approved therapies that can halt or reverse the clinical progression of AD. Traditionally, AD is characterized first by the appearance of amyloid-β (Aβ) plaques followed by the formation of intraneuronal neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau (p-tau). These lesions are linked to synapse loss and eventual cognitive impairment. Additionally, microgliosis is consistently found in regions of the brain with AD pathology. The role of microglia in AD onset and progression remains unclear. Several recent reports indicate that the assembly of the multi-protein complex known as the NOD, LRR, and pyrin-domain containing 3 (Nlrp3) inflammasome by microglia results in apoptosis spec-like protein containing a CARD (Asc) spec formation, which then nucleates new Aβ plaques, thus amplifying Aβ-associated pathology. NFTs can also activate the Nlrp3 inflammasome leading to enhanced tau-associated pathology. Here, we will review the role of microglia and the activation of the inflammasome in the innate immune response to AD.
TL;DR: A previous perception of a trend toward a lower overall risk of cancer in patients with MS appears to be challenged, but there is no evidence on any higher occurrence of malignancies in the population with MS.
Abstract: Comorbidities in patients with multiple sclerosis (MS) has become an area of increasing interest in the recent years. A comorbidity is defined as any additional disease that coexists in an individual with a given index disease and that is not an obvious complication of the index disease. The aim of this review is to describe the current evidence regarding the range of comorbidities in the population with MS reported in different countries and the current knowledge about the influence of comorbidities on the clinical features and therapeutic challenges in MS. Certain comorbidities are more prevalent in people with MS such as depression, anxiety, cerebro- and cardiovascular diseases, and certain autoimmune disorders such as diabetes, thyroid disease, and inflammatory bowel disease. A previous perception of a trend toward a lower overall risk of cancer in patients with MS appears to be challenged, but there is no evidence on any higher occurrence of malignancies in the population with MS. Comorbidities may modify the clinical presentation of MS, and have implications for treatment choice, adherence, and outcome. Several comorbid conditions are associated with increased disability progression, including diabetes, hypertension, and chronic obstructive pulmonary disease. Comorbidities are common in MS from the time of diagnosis and may account for some of the heterogeneity observed in MS, including diagnostic delay, clinical presentation, degree of disability progression, rate of health care utilization, working ability, employment status, and quality of life. Coexisting diseases and polypharmacy increase the complexity of patient management and poses major challenges, particularly with the increasing number of immunosuppressive disease-modifying therapies.
TL;DR: This review is aimed to summarize the updated knowledge on the typical and atypical clinical and imaging features, prognostic markers and gaps in literature for future research on Posterior reversible encephalopathy syndrome.
Abstract: Background: Posterior reversible encephalopathy syndrome (PRES) is an acute neurotoxic syndrome that is characterized by a spectrum neurological and radiological feature from various risk factors. Common neurological symptoms includes headache, impairment in level of consciousness, seizures, visual disturbances, and focal neurological deficits. Common triggering factors include blood pressure fluctuations, renal failure, eclampsia, exposure to immunosuppressive or cytotoxic agents and autoimmune disorders. The classic radiographic findings include bilateral subcortical vasogenic edema predominantly affecting the parieto-occipital regions but atypical features include involvement of other regions, cortical involvement, restricted diffusion, hemorrhage, contrast enhancement. This review is aimed to summarize the updated knowledge on the typical and atypical clinical and imaging features, prognostic markers and identify gaps in literature for future research. Methods: Systematic literature review using PUBMED search from 1990 to 2019 was performed using terms PRES was performed. Results: While clinical and radiographic reversibility is common, long-standing morbidity and mortality can occur in severe forms. In patients with malignant forms of PRES, aggressive care has markedly reduced mortality and improved functional outcomes. Although seizures were common, epilepsy is rare. Various factors that have been associated with poor outcome include altered sensorium, hypertensive etiology, hyperglycemia, longer time to control the causative factor, elevated C reactive protein, coagulopathy, extensive cerebral edema, and hemorrhage on imaging. Conclusion: Large prospective studies that accurately predict factors that are associated with poor outcomes, determine the pathophysiology, and targeted therapy are required.
TL;DR: The data suggest that the α-synuclein level in serum or plasma can differentiate between healthy controls and patients with PD, and moderately correlate with motor severity in patients with early PD.
Abstract: Background: Parkinson's disease (PD) is the second most common neurodegenerative disease, and α-synuclein plays a critical role in the pathogenesis of PD. Studies have revealed controversial results regarding the correlation between motor severity and α-synuclein levels in peripheral blood from patients with PD. Objective: We examined α-synuclein levels in plasma or serum in patients with PD and investigated the relationship between plasma or serum α-synuclein level and motor symptom severity. Methods: We recruited 88 participants (48 patients with PD and 40 healthy controls). Clinical information was collected, and venous blood was drawn from each participant to be processed to obtain plasma or serum. The plasma or serum α-synuclein level was detected using monoclonal antibodies with magnetic nanoparticles, and was measured through immunomagnetic reduction. Plasma or serum α-synuclein levels were quantitatively detected. Results: In patients with PD, the means of plasma and serum α-synuclein level were 3.60 ± 2.53 and 0.03 ± 0.04 pg/mL, respectively. The areas under the receiver operating characteristic curve of plasma and serum α-synuclein for distinguishing patients with PD from healthy controls were 0.992 and 0.917, respectively. The serum α-synuclein level also showed a significant correlation with patients in H-Y stages 1-3 (r = 0.40, p = 0.025), implying that the serum α-synuclein level may be a potential marker of motor symptom severity in patients with early PD. Conclusions: Our data suggest that the α-synuclein level in serum or plasma can differentiate between healthy controls and patients with PD. Serum α-synuclein levels moderately correlate with motor severity in patients with early PD.
TL;DR: It is hypothesized that cannabinoid 2 receptor (CB2R) signaling shifts the balance of expression between neuroinflammatory genes, neuroprotective genes, and homeostatic genes toward the latter two gene expressions, by which microglia acquire therapeutic functionality.
Abstract: Microglia, the resident immune cells of the central nervous system, mediate brain homeostasis by controlling neuronal proliferation/differentiation and synaptic activity. In response to external signals from neuropathological conditions, homeostatic (M0) microglia can adopt one of two activation states: the classical (M1) activation state, which secretes mediators of the proinflammatory response, and the alternative (M2) activation state, which presumably mediates the resolution of neuroinflammation and tissue repair/remodeling. Since chronic inflammatory activation of microglia is correlated with several neurodegenerative diseases, functional modulation of microglial phenotypes has been considered as a potential therapeutic strategy. The endocannabinoid (eCB) system, composed of cannabinoid receptors and ligands and their metabolic/biosynthetic enzymes, has been shown to activate anti-inflammatory signaling pathways that modulate immune cell functions. Growing evidence has demonstrated that endogenous, synthetic, and plant-derived eCB agonists possess therapeutic effects on several neuropathologies; however, the molecular mechanisms that mediate the anti-inflammatory effects have not yet been identified. Over the last decade, it has been revealed that the eCB system modulates microglial activation and population. In this review, we thoroughly examine recent studies on microglial phenotype modulation by eCB in neuroinflammatory and neurodegenerative disease conditions. We hypothesize that cannabinoid 2 receptor (CB2R) signaling shifts the balance of expression between neuroinflammatory (M1-type) genes, neuroprotective (M2-type) genes, and homeostatic (M0-type) genes toward the latter two gene expressions, by which microglia acquire therapeutic functionality.
TL;DR: It is suggested that rTMS is beneficial for treating neuropathic pain of various origins, such as central pain, pain from peripheral nerve disorders, fibromyalgia, and migraine.
Abstract: Recently, clinicians have been using repetitive transcranial magnetic stimulation (rTMS) for treating various pain conditions. This systematic narrative review aimed to examine the use and efficacy of rTMS for controlling various pain conditions. A PubMed search was conducted for articles that were published until June 7, 2019 and used rTMS for pain alleviation. The key search phrase for identifying potentially relevant articles was (repetitive transcranial magnetic stimulation AND pain). The following inclusion criteria were applied for article selection: (1) patients with pain, (2) rTMS was applied for pain management, and (3) follow-up evaluations were performed after rTMS stimulation to assess the reduction in pain. Review articles were excluded. Overall, 1,030 potentially relevant articles were identified. After reading the titles and abstracts and assessing eligibility based on the full-text articles, 106 publications were finally included in our analysis. Overall, our findings suggested that rTMS is beneficial for treating neuropathic pain of various origins, such as central pain, pain from peripheral nerve disorders, fibromyalgia, and migraine. Although data on the use of rTMS for orofacial pain, including trigeminal neuralgia, phantom pain, low back pain, myofascial pain syndrome, pelvic pain, and complex regional pain syndrome, were promising, there was insufficient evidence to determine the efficacy of rTMS for treating these conditions. Therefore, further studies are needed to validate the effects of rTMS on pain relief in these conditions. Overall, this review will help guide clinicians in making informed decisions regarding whether rTMS is an appropriate option for managing various pain conditions.
TL;DR: Most patients with MG hospitalized for COVID-19 had severe courses of the disease: 87% were admitted in the intensive care unit, 73% needed mechanical ventilation, and 30% died.
Abstract: Myasthenia gravis (MG), an autoimmune neuromuscular disorder, may be a risk factor for severe COVID-19. We conducted an observational retrospective study with 15 consecutive adult MG patients admitted with COVID-19 at four hospitals in Sao Paulo, Brazil. Most patients with MG hospitalized for COVID-19 had severe courses of the disease: 87% were admitted in the intensive care unit, 73% needed mechanical ventilation, and 30% died. Immunoglobulin use and the plasma exchange procedure were safe. Immunosuppressive therapy seems to be associated with better outcomes, as it might play a protective role.
TL;DR: The role of astrocyte-related processes in epileptogenesis, including reactive astrogliosis, disturbances in energy supply and metabolism, gliotransmission, and extracellular ion concentrations, as well as blood-brain barrier dysfunction and dysregulation of blood flow are discussed.
Abstract: Astrocytes are key homeostatic regulators in the central nervous system and play important roles in physiology. After brain damage caused by e.g., status epilepticus, traumatic brain injury, or stroke, astrocytes may adopt a reactive phenotype. This process of reactive astrogliosis is important to restore brain homeostasis. However, persistent reactive astrogliosis can be detrimental for the brain and contributes to the development of epilepsy. In this review, we will focus on physiological functions of astrocytes in the normal brain as well as pathophysiological functions in the epileptogenic brain, with a focus on acquired epilepsy. We will discuss the role of astrocyte-related processes in epileptogenesis, including reactive astrogliosis, disturbances in energy supply and metabolism, gliotransmission, and extracellular ion concentrations, as well as blood-brain barrier dysfunction and dysregulation of blood flow. Since dysfunction of astrocytes can contribute to epilepsy, we will also discuss their role as potential targets for new therapeutic strategies.
TL;DR: The spectrum of behavioral disturbances differs between TBI severity categories and serious behavioral disturbances are present in a quarter of patients, suggesting that particularly the presence and not the severity of long-term behavioral disturbances interferes with RTW.
Abstract: Introduction: Behavioral disturbances are found in 50-60% of traumatic brain injury (TBI) survivors with an enormous impact on daily functioning and level of recovery. However, whether typical profiles can be distinguished and how these relate to provided care is unclear. The purpose of this study is to specify the characteristics of behavioral disturbances in patients with various severity of TBI and the impact on functional outcome. Furthermore, the pathways of care after hospital discharge for patients and their care givers are analyzed. Methods: We performed a retrospective cohort study comprising 226 patients with mild TBI (mTBI; n = 107) and moderate-to-severe TBI (mod/sevTBI; n = 119) treated at the outpatient clinic and/or rehabilitation center of our university hospital between 2010 and 2015. Inclusion criteria were: behavioral disturbances as determined with the Differential Outcome Scale and age >= 16 years. Functional outcome was determined by the Glasgow Outcome Scale Extended and return to work (RTW) at six months to one year post-injury. Behavioral impairments and pathway of care were derived from medical files and scored according to predefined criteria. Results: Overall 24% of patients showed serious behavioral disturbances; three times higher in mod/sevTBI (35%) compared to mTBI (13%). mTBI patients mostly showed irritation (82%) and anger (49%), while mod/sevTBI patients mostly showed irritation (65%) and disinhibition (55%). Most (92%) patients returned home, half of the patients did not RTW. Deficits in judgment and decision-making increased risk of no RTW 10-fold. One in ten patients was (temporarily) admitted to a nursing home or psychiatric institution. 13% Of caregivers received support for dealing with impairments of patients and 13% of the mTBI and 17% of the mod/sevTBI patients experienced relational problems. Conclusions: The spectrum of behavioral disturbances differs between TBI severity categories and serious behavioral disturbances are present in a quarter of patients. Only half of the patients resumed work regardless of severity of injury suggesting that particularly the presence and not the severity of long-term behavioral disturbances interferes with RTW. Most patients returned home despite these behavioral disturbances. These findings underline the importance of early identification and appropriate treatment of behavioral disturbances in TBI patients.
TL;DR: Clinical, neuroradiological features and controversies underlying both syndromes that may mislead the diagnostic pathway and their possible relationship with pathophysiology, clinical course, and prognosis are summarized.
Abstract: Posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS) are relatively uncommon neurological disorders, but their detection has been increasing mainly due to clinical awareness and spreading of magnetic resonance imaging (MRI). Because these syndromes share some common clinical and radiologic features and occasionally occur in the same patient, misdiagnosis may occur. PRES is characterized by varied neurological symptoms including headache, impaired visual acuity or visual field deficit, confusion, disorders of consciousness, seizures, and motor deficits often associated to peculiar neuroradiological pattern even if uncommon localization and ischemic or hemorrhagic lesions were described. RCVS is a group of diseases typically associated with severe headaches and reversible segmental vasoconstriction of cerebral arteries, often complicated by ischemic or hemorrhagic stroke. Pathophysiological basis of PRES and RCVS are still debated but, because they share some risk factors and clinical features, a possible common origin has been supposed. Clinical course is usually self-limiting, but prognosis may fluctuate from complete recovery to death due to complications of ischemic stroke or intracranial hemorrhage. Neuroradiological techniques such as digital angiography and MRI are helpful in the diagnostic pathway and a possible prognostic role of MRI has been suggested. This review will serve to summarize clinical, neuroradiological features and controversies underlying both syndromes that may mislead the diagnostic pathway and their possible relationship with pathophysiology, clinical course, and prognosis.
TL;DR: The presence of CND is an independent predictor of mortality in hospitalized Covid-19 patients, and that was not explained neither by a worse immune response to Covod-19 nor by differences in the level of care received by patients with CND.
Abstract: Introduction Prognosis of Coronavirus disease 2019 (Covid-19) patients with vascular risk factors, and certain comorbidities is worse. The impact of chronic neurological disorders (CND) on prognosis is unclear. We evaluated if the presence of CND in Covid-19 patients is a predictor of a higher in-hospital mortality. As secondary endpoints, we analyzed the association between CND, Covid-19 severity, and laboratory abnormalities during admission. Methods: Retrospective cohort study that included all the consecutive hospitalized patients with confirmed Covid-19 disease from March 8th to April 11th, 2020. The study setting was Hospital Clinico, tertiary academic hospital from Valladolid. CND was defined as those neurological conditions causing permanent disability. We assessed demography, clinical variables, Covid-19 severity, laboratory parameters and outcome. The primary endpoint was in-hospital all-cause mortality, evaluated by multivariate cox-regression log rank test. We analyzed the association between CND, covid-19 severity and laboratory abnormalities. Results: We included 576 patients, 43.3% female, aged 67.2 years in mean. CND were present in 105 (18.3%) patients. Patients with CND were older, more disabled, had more vascular risk factors and comorbidities and fewer clinical symptoms of Covid-19. They presented 1.43 days earlier to the emergency department. Need of ventilation support was similar. Presence of CND was an independent predictor of death (HR 2.129, 95% CI: 1.382-3.280) but not a severer Covid-19 disease (OR: 1.75, 95% CI: 0.970-3.158). Frequency of laboratory abnormalities was similar, except for procalcitonin and INR. Conclusions: The presence of CND is an independent predictor of mortality in hospitalized Covid-19 patients. That was not explained neither by a worse immune response to Covid-19 nor by differences in the level of health care received by patients with CND.
TL;DR: The increasing incidence of olfactory/taste disorders, myalgia, headache, and acute cerebral vascular disease renders a possibility that COVID-19 could attack the nervous system.
Abstract: Objective: Review and integrate the neurologic manifestations of the Coronavirus Disease 2019 (COVID-19) pandemic, to aid medical practitioners who are combating the newly derived infectious disease. Methods: We reviewed the clinical research, consisting of mainly case series, on reported neurologic manifestations of COVID-19. We also reviewed basic studies to understand the mechanism of these neurologic symptoms and signs. Results: We included 79 studies for qualitative synthesis and 63 studies for meta-analysis. The reported neurologic manifestations were olfactory/taste disorders (35.6%), myalgia (18.5%), headache (10.7%), acute cerebral vascular disease (8.1%), dizziness (7.9%), altered mental status (7.8%), seizure (1.5%), encephalitis, neuralgia, ataxia, Guillain-Barre syndrome, Miller Fisher syndrome, intracerebral hemorrhage, polyneuritis cranialis, and dystonic posture. Conclusions: Neurologic manifestations in COVID-19 may alert physicians and medical practitioners to rule in high-risk patients. The increasing incidence of olfactory/taste disorders, myalgia, headache, and acute cerebral vascular disease renders a possibility that COVID-19 could attack the nervous system. The cytokine secretion and bloodstream circulation (viremia) are among the most possible routes into the nervous system.
University of New South Wales1, Tel Aviv University2, University of Toronto3, University Hospitals Birmingham NHS Foundation Trust4, Loyola University Chicago5, Australian National University6, University of Eastern Piedmont7, University College London8, Bombay Hospital, Indore9, Anton de Kom University of Suriname10, Eastern Illinois University11, King's College London12, University of Paris III: Sorbonne Nouvelle13
TL;DR: An in-depth analysis of the impact of COVID-19 on chronic neurological conditions and specific recommendations to minimize the potential harm to those at high risk are provided.
Abstract: With the rapid pace and scale of the emerging coronavirus 2019 (COVID-19) pandemic, a growing body of evidence has shown a strong association of COVID-19 with pre- and post- neurological complications. This has necessitated the need to incorporate targeted neurological care for this subgroup of patients which warrants further reorganization of services, healthcare workforce, and ongoing management of chronic neurological cases. The social distancing and the shutdown imposed by several nations in the midst of COVID-19 have severely impacted the ongoing care, access and support of patients with chronic neurological conditions such as Multiple Sclerosis, Epilepsy, Neuromuscular Disorders, Migraine, Dementia, and Parkinson disease. There is a pressing need for governing bodies including national and international professional associations, health ministries and health institutions to harmonize policies, guidelines, and recommendations relating to the management of chronic neurological conditions. These harmonized guidelines should ensure patient continuity across the spectrum of hospital and community care including the well-being, safety, and mental health of the patients, their care partners and the health professionals involved. This article provides an in-depth analysis of the impact of COVID-19 on chronic neurological conditions and specific recommendations to minimize the potential harm to those at high risk.
TL;DR: The spectrum of neurological findings associated with COVID-19 is summarized, which include signs of peripheral neuropathy, myopathy, olfactory dysfunction, meningoencephalitis, Guillain-Barré syndrome, and neuropsychiatric disorders, and the mechanisms underlying such neurological sequela are analyzed.
Abstract: The human infection of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a public health emergency of international concern that has caused more than 16.8 million new cases and 662,000 deaths as of July 30, 2020. Although coronavirus disease 2019 (COVID-19), which is associated with this virus, mainly affects the lungs, recent evidence from clinical and pathological studies indicates that this pathogen has a broad infective ability to spread to extrapulmonary tissues, causing multiorgan failure in severely ill patients. In this regard, there is increasing preoccupation with the neuroinvasive potential of SARS-CoV-2 due to the observation of neurological manifestations in COVID-19 patients. This concern is also supported by the neurotropism previously documented in other human coronaviruses, including the 2002-2003 SARS-CoV-1 outbreak. Hence, in the current review article, we aimed to summarize the spectrum of neurological findings associated with COVID-19, which include signs of peripheral neuropathy, myopathy, olfactory dysfunction, meningoencephalitis, Guillain-Barre syndrome, and neuropsychiatric disorders. Furthermore, we analyze the mechanisms underlying such neurological sequela and discuss possible therapeutics for patients with neurological findings associated with COVID-19. Finally, we describe the host- and pathogen-specific factors that determine the tissue tropism of SARS-CoV-2 and possible routes employed by the virus to invade the nervous system from a pathophysiological and molecular perspective. In this manner, the current manuscript contributes to increasing the current understanding of the neurological aspects of COVID-19 and the impact of the current pandemic on the neurology field.
TL;DR: The approach to prodromal PD is reviewed, with an emphasis on clinical and imaging markers and results from the neuroimaging study, a retrospective evaluation of a cohort of 39 participants who underwent DAT-SPECT scan as part of their follow up.
Abstract: The diagnosis of Parkinson's disease (PD) relies on the clinical effects of dopamine deficiency, including bradykinesia, rigidity and tremor, usually manifesting asymmetrically. Misdiagnosis is common, due to overlap of symptoms with other neurodegenerative disorders such as multiple system atrophy and progressive supranuclear palsy, and only autopsy can definitively confirm the disease. Motor deficits generally appear when 50-60% of dopaminergic neurons in the substantia nigra are already lost, limiting the effectiveness of potential neuroprotective therapies. Today, we consider PD to be not just a movement disorder, but rather a complex syndrome non-motor symptoms (NMS) including disorders of sleep-wake cycle regulation, cognitive impairment, disorders of mood and affect, autonomic dysfunction, sensory symptoms and pain. Symptomatic LRRK2 mutation carriers share non-motor features with individuals with sporadic PD, including hyposmia, constipation, impaired color discrimination, depression, and sleep disturbance. Following the assumption that the pre-symptomatic gene mutation carriers will eventually exhibit clinical symptoms, their neuroimaging results can be extended to the pre-symptomatic stage of PD. The long latent phase of PD, termed prodromal-PD, represents an opportunity for early recognition of incipient PD. Early recognition could allow initiation of possible neuroprotective therapies at a stage when therapies might be most effective. The number of markers with the sufficient level of evidence to be included in the MDS research criteria for prodromal PD have increased during the last 10 years. Here, we review the approach to prodromal PD, with an emphasis on clinical and imaging markers and report results from our neuroimaging study, a retrospective evaluation of a cohort of 39 participants who underwent DAT-SPECT scan as part of their follow up. The study was carried out to see if it was possible to detect subclinical signs in the preclinical (neurodegenerative processes have commenced, but there are no evident symptoms or signs) and prodromal (symptoms and signs are present, but are yet insufficient to define disease) stages of PD.
TL;DR: A new deep learning-based classification methodology, namely epileptic EEG signal classification (EESC), is proposed in this paper, which outperforms the existing epilepsy classification methods in terms of accuracy and efficiency.
Abstract: Electroencephalogram (EEG) signals contain vital information on the electrical activities of the brain and are widely used to aid epilepsy analysis. A challenging element of epilepsy diagnosis, accurate classification of different epileptic states, is of particular interest and has been extensively investigated. A new deep learning-based classification methodology, namely epileptic EEG signal classification (EESC), is proposed in this paper. This methodology first transforms epileptic EEG signals to power spectrum density energy diagrams (PSDEDs), then applies deep convolutional neural networks (DCNNs) and transfer learning to automatically extract features from the PSDED, and finally classifies four categories of epileptic states (interictal, preictal duration to 30 min, preictal duration to 10 min, and seizure). It outperforms the existing epilepsy classification methods in terms of accuracy and efficiency. For instance, it achieves an average classification accuracy of over 90% in a case study with CHB-MIT epileptic EEG data.
TL;DR: The potential for NKCC1 and KCC2 to be therapeutic targets for the development of novel antiepileptic drugs is explored and its implications on the treatment of epilepsy are explored.
Abstract: As a main inhibitory neurotransmitter in the central nervous system, γ-aminobutyric acid (GABA) activates chloride-permeable GABAa receptors (GABAa Rs) and induces chloride ion (Cl-) flow, which relies on the intracellular chloride concentration ([Cl-]i) of the postsynaptic neuron. The Na-K-2Cl cotransporter isoform 1 (NKCC1) and the K-Cl cotransporter isoform 2 (KCC2) are two main cation-chloride cotransporters (CCCs) that have been implicated in human epilepsy. NKCC1 and KCC2 reset [Cl-]i by accumulating and extruding Cl-, respectively. Previous studies have shown that the profile of NKCC1 and KCC2 in neonatal neurons may reappear in mature neurons under some pathophysiological conditions, such as epilepsy. Although increasing studies focusing on the expression of NKCC1 and KCC2 have suggested that impaired chloride plasticity may be closely related to epilepsy, additional neuroelectrophysiological research aimed at studying the functions of NKCC1 and KCC2 are needed to understand the exact mechanism by which they induce epileptogenesis. In this review, we aim to briefly summarize the current researches surrounding the expression and function of NKCC1 and KCC2 in epileptogenesis and its implications on the treatment of epilepsy. We will also explore the potential for NKCC1 and KCC2 to be therapeutic targets for the development of novel antiepileptic drugs.
TL;DR: There is paucity of data on telere rehabilitation in the Philippines and local efforts can focus on exploring or addressing the most pressing human, organizational, and technical challenges to the emergence of telerehabilitation in the country.
Abstract: Background: Despite being known abroad as a viable alternative to face-to-face consultation and therapy, telerehabilitation has not fully emerged in developing countries like the Philippines. In the midst of the coronavirus disease 2019 (COVID-19) pandemic, wherein social distancing disrupted the in-clinic delivery of rehabilitation services, Filipinos attempted to explore telerehabilitation. However, several hindrances were observed especially during the pre-implementation phase of telerehabilitation, necessitating a review of existing local evidences. Objective: We aimed to determine the challenges faced by telerehabilitation in the Philippines. Method: We searched until March 2020 through PubMed, Scopus, Embase, Cochrane Library, and HeRDIN for telerehabilitation-related publications wherein Filipinos were involved as investigator or population. Because of the hypothesized low number of scientific outputs on telerehabilitation locally, we performed handsearching through gray literature and included relevant papers from different rehabilitation-related professional organizations in the Philippines. We analyzed the papers and extracted the human, organizational, and technical challenges to telerehabilitation or telehealth in general. Results: We analyzed 21 published and 4 unpublished papers, which were mostly reviews (8), feasibility studies (6), or case reports/series (4). Twelve out of 25 studies engaged patients and physicians in remote teleconsultation, teletherapy, telementoring, or telemonitoring. Patients sought telemedicine or telerehabilitation for general medical conditions (in 3 studies), chronic diseases (2), mental health issues (2), orthopedic problems (2), neurologic conditions (1), communication disorders (1), and cardiac conditions (1). Outcomes in aforementioned studies mostly included telehealth acceptance, facilitators, barriers, and satisfaction. Other studies were related to telehealth governance, legalities, and ethical issues. We identified 18 human, 17 organizational, and 18 technical unique challenges related to telerehabilitation in the Philippines. The most common challenges were slow internet speed (in 10 studies), legal concerns (9), and skepticism (9). Conclusion: There is paucity of data on telerehabilitation in the Philippines. Local efforts can focus on exploring or addressing the most pressing human, organizational, and technical challenges to the emergence of telerehabilitation in the country.
TL;DR: It was identified that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic had a significant impact on the psychological status of patients with MS.
Abstract: Objective: The coronavirus disease 2019 (COVID-19) has radically changed the world in a few weeks. Italy has been one of the first and most affected countries with more than 30,000 deaths up to now. Public health measures as quarantine or national lockdown are necessary to limit the spread of infectious diseases, but it is unsurprising that depriving people of their liberty has negative psychological effects. This is especially the case for people with chronic diseases, including neurological conditions like multiple sclerosis (MS). People with MS (PwMS) have a higher burden of neuropsychiatric comorbidities and are known to undertake maladaptive coping strategies in stress conditions. The aim of the present study is to investigate the impact of COVID-19 pandemic lockdown on mental health of an Italian cohort of PwMS in comparison with healthy controls (HCs). Methods: A total of 60 PwMS and 50 HCs (chosen among patients' cohabitants) were asked to answer a Web-based survey. This survey inquired about the impact of COVID-19 on patient's quality of life, job, and daily routine. Mood, fatigue, and sleep quality were evaluated using the Beck Depression Inventory II (BDI-II), the Generalized Anxiety Disease 7 (GAD-7), the Fatigue Severity Scale (FSS), and the Pittsburgh Sleep Quality Index (PSQI). Results: Overall, patients had higher scores of BDI, FSS, and PSQI, and these differences were statistically significant (p < 0.05). When we looked at the subscores of the BDI, we detected a statistically significant difference for the neurovegetative part-that concerns with sleep, appetite, sex, and quality of sleep (p < 0.05). One out of five patients reported new symptoms or worsening of known symptom, in particular, sensory disturbances, and fatigue. However, no symptoms were severe enough to require hospitalization. When we looked for correlations among variables, we found that there was a significant relationship between unemployment and BDI total score, GAD-7, and PSQI in MS group. The presence of new symptoms or the worsening of symptoms positively related to FSS and to PSQI. Discussion: We identified that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic had a significant impact on the psychological status of patients with MS. Compared with the general population, PwMS presented a higher burden of depressive symptoms, a worse sleep quality and perceived an increase in fatigue level, one of the most disabling symptoms of MS. The COVID-19 epidemic poses a challenge to psychological resilience. More studies are warranted to better understand the long-term consequences of the pandemic on mental health of vulnerable people during the disease outbreaks.