Showing papers in "Neurological Sciences in 2020"

Neuroinvasion, neurotropic, and neuroinflammatory events of SARS-CoV-2: understanding the neurological manifestations in COVID-19 patients.

Abstract: Respiratory viruses are opportunistic pathogens that infect the upper respiratory tract in humans and cause severe illnesses, especially in vulnerable populations. Some viruses have neuroinvasive properties and activate the immune response in the brain. These immune events may be neuroprotective or they may cause long-term damage similar to what is seen in some neurodegenerative diseases. The new "Severe Acute Respiratory Syndrome Coronavirus 2" (SARS-CoV-2) is one of the Respiratory viruses causing highly acute lethal pneumonia coronavirus disease 2019 (COVID-19) with clinical similarities to those reported in "Severe Acute Respiratory Syndrome Coronavirus"(SARS-CoV) and the "Middle East Respiratory Syndrome Coronavirus"(MERS-CoV) including neurological manifestation. To examine the possible neurological damage induced by SARS-CoV-2, it is necessary to understand the immune reactions to viral infection in the brain, and their short- and long-term consequences. Considering the similarities between SARS-CoV and SARS-CoV-2, which will be discussed, cooperative homological and phylogenetical studies lead us to question if SARS-CoV-2 can have similar neuroinvasive capacities and neuroinflammatiory events that may lead to the same short- and long-term neuropathologies that SARS-CoV had shown in human and animal models. To explain the neurological manifestation caused by SARS-CoV-2, we will present a literature review of 765 COVID-19 patients, in which 18% had neurological symptoms and complications, including encephalopathy, encephalitis and cerebrovascular pathologies, acute myelitis, and Guillain-Barre syndrome. Clinical studies describe anosmia or partial loss of the sense of smell as the most frequent symptom in COVID19 patients, suggesting that olfactory dysfunction and the initial ultrarapid immune responses could be a prognostic factor.

The neurological manifestations of COVID-19: a review article.

Abstract: Various neurological manifestations have been reported in the literature associated with COVID-19, which in the current study are classified into Central Nervous System (CNS) related manifestations including headache, dizziness, impaired consciousness, acute cerebrovascular disease, epilepsy, and Peripheral Nervous System (PNS) related manifestations such as hyposmia/anosmia, hypogeusia/ageusia, muscle pain, and Guillain-Barre syndrome. During the current context of COVID-19 pandemic, physicians should be aware of wide spectrum of neurological COVID-19 sign and symptoms for early diagnosis and isolation of patients. In this regard, COVID-19 has been associated with many neurological manifestations such as confusion, anosmia, and ageusia. Also, various evidences support the possible CNS roles in the COVID-19 pathophysiology. In this regard, further investigation of CNS involvement of SARS-COV-2 is suggested.

Neuromuscular presentations in patients with COVID-19.

Abstract: COVID-19 is caused by the coronavirus SARS-CoV-2 that has an affinity for neural tissue. There are reports of encephalitis, encephalopathy, cranial neuropathy, Guillain-Barre syndrome, and myositis/rhabdomyolysis in patients with COVID-19. In this review, we focused on the neuromuscular manifestations of SARS-CoV-2 infection. We analyzed all published reports on SARS-CoV-2-related peripheral nerve, neuromuscular junction, muscle, and cranial nerve disorders. Olfactory and gustatory dysfunction is now accepted as an early manifestation of COVID-19 infection. Inflammation, edema, and axonal damage of olfactory bulb have been shown in autopsy of patients who died of COVID-19. Olfactory pathway is suggested as a portal of entry of SARS-CoV-2 in the brain. Similar to involvement of olfactory bulb, isolated oculomotor, trochlear and facial nerve has been described. Increasing reports Guillain-Barre syndrome secondary to COVID-19 are being published. Unlike typical GBS, most of COVID-19-related GBS were elderly, had concomitant pneumonia or ARDS, more prevalent demyelinating neuropathy, and relatively poor outcome. Myalgia is described among the common symptoms of COVID-19 after fever, cough, and sore throat. Duration of myalgia may be related to the severity of COVID-19 disease. Few patients had muscle weakness and elevated creatine kinase along with elevated levels of acute-phase reactants. All these patients with myositis/rhabdomyolysis had severe respiratory complications related to COVID-19. A handful of patients with myasthenia gravis showed exacerbation of their disease after acquiring COVID-19 disease. Most of these patients recovered with either intravenous immunoglobulins or steroids.

Acute stroke management pathway during Coronavirus-19 pandemic.

Abstract: Since the outbreak of the COVID-19 epidemic which in our region, Veneto (Italy), dates back to February, we were confronted with several challenges, but with a constant aim of keeping our Stroke Unit COVID-free. For this reason, in addition to creating a dedicated hot-spot as a pre-triage just outside the Emergency Department, together with the Neuroradiology Unit we obtained a mobile CT unit that could be used by COVID-positive or COVID-suspected patients. Furthermore, thanks to the collaboration with colleagues from different specialties (Infectious Disease, Internal Medicine, Intensive Care, Emergency Medicine), dedicated areas for COVID patients were activated. This led to a substantial change of our acute stoke management pathway. As the number of COVID patients increased, and the WHO declared a state of pandemic, this new stroke pathway has been fully tested. We would like to share our experience and send a clear message to keep a high attention on stroke as an emergency condition, because we have observed a decreased number of patients with minor strokes and TIAs, longer onset-to-door and door-to-treatment times for major strokes, and a reduced number of transfers from spokes. We strongly believe that the general population and family doctors are rightly focused on COVID. However, to remain at home with stroke symptoms does not mean to "stay safe at home".

Neurological manifestations of COVID-19: a systematic review and meta-analysis of proportions.

Abstract: Coronaviruses mainly affect the respiratory system; however, there are reports of SARS-CoV and MERS-CoV causing neurological manifestations. We aimed at discussing the various neurological manifestations of SARS-CoV-2 infection and to estimate the prevalence of each of them. We searched the following electronic databases; PubMed, MEDLINE, Scopus, EMBASE, Google Scholar, EBSCO, Web of Science, Cochrane Library, WHO database, and ClinicalTrials.gov . Relevant MeSH terms for COVID-19 and neurological manifestations were used. Randomized controlled trials, non-randomized controlled trials, case-control studies, cohort studies, cross-sectional studies, case series, and case reports were included in the study. To estimate the overall proportion of each neurological manifestations, the study employed meta-analysis of proportions using a random-effects model. Pooled prevalence of each neurological manifestations are, smell disturbances (35.8%; 95% CI 21.4–50.2), taste disturbances (38.5%; 95%CI 24.0–53.0), myalgia (19.3%; 95% CI 15.1–23.6), headache (14.7%; 95% CI 10.4–18.9), dizziness (6.1%; 95% CI 3.1–9.2), and syncope (1.8%; 95% CI 0.9–4.6). Pooled prevalence of acute cerebrovascular disease was (2.3%; 95%CI 1.0–3.6), of which majority were ischaemic stroke (2.1%; 95% CI 0.9–3.3), followed by haemorrhagic stroke (0.4%; 95% CI 0.2–0.6), and cerebral venous thrombosis (0.3%; 95% CI 0.1–0.6). Neurological symptoms are common in SARS-CoV-2 infection, and from the large number of cases reported from all over the world daily, the prevalence of neurological features might increase again. Identifying some neurological manifestations like smell and taste disturbances can be used to screen patients with COVID-19 so that early identification and isolation is possible.

Dementia care and COVID-19 pandemic: a necessary digital revolution.

Abstract: Due to the COVID-19 pandemic, most memory clinics have had to suspend their activities. On the other hand, international dementia experts have recommended to provide urgently worldwide support for people living with dementia. This situation urges to play out new strategies to guarantee adequate care. Telemedicine and digital technology (DT) devices, such as smartphones, can be very helpful in remote monitoring and care. Technological devices such as videoconference or smartphone apps might be used for follow-up visits and support to patients and caregivers and to acquire digital markers of clinical progression. Hopefully, this dramatic situation would facilitate the process of progressive familiarization of neurologists with telemedicine and DT approach.

Early Guillain-Barré syndrome in coronavirus disease 2019 (COVID-19): a case report from an Italian COVID-hospital.

Abstract: Guillain-Barre syndrome (GBS) is an acute polyradiculoneuropathy associated with dysimmune processes, often related to a previous infectious exposure. During Italian severe acute respiratory syndrome coronavirus-2 outbreak, a woman presented with a rapidly progressive flaccid paralysis with unilateral facial neuropathy after a few days of mild respiratory symptoms. Coronavirus was detected by nasopharyngeal swab, but there was no evidence of its presence in her cerebrospinal fluid, which confirmed the typical albumin-cytological dissociation of GBS, along with consistent neurophysiological data. Despite immunoglobulin infusions and intensive supportive care, her clinical picture worsened simultaneously both from the respiratory and neurological point of view, as if reflecting different aspects of the same systemic inflammatory response. Similar early complications have already been observed in patients with para-infectious GBS related to Zika virus, but pathological mechanisms have yet to be established.

A prospective clinical study of detailed neurological manifestations in patients with COVID-19.

Abstract: COVID-19 is a virus pandemic According to the first obtained data, COVID-19 has defined with findings such as cough, fever, diarrhea, and fatigue although neurological symptoms of patients with COVID-19 have not been investigated in detail This study aims to investigate the neurological findings via obtained face-to-face anamnesis and detailed neurological examination in patients with COVID-19 Two hundred thirty-nine consecutive inpatients with COVID-19, supported with laboratory tests, were evaluated Detailed neurological examinations and evaluations of all patients were performed All evaluations and examinations were performed by two neurologists who have at least five-year experience This study was carried out 239 patients (133 male + 106 female) with diagnosed COVID-19 Neurological findings were present in 83 of 239 patients (347%) The most common neurological finding was a headache (276%) D-dimer blood levels were detected to be significantly higher in patients with at least one neurological symptom than patients without the neurological symptom (p < 005) IL-6 level was found to be significantly higher in patients with headache than without headache (p < 005) Creatine kinase (CK) level was detected to be significantly higher in patients with muscle pain (p < 005) Neurological symptoms are often seen in patients with COVID-19 Headache was the most common seen neurological symptom in this disease Dizziness, impaired consciousness, smell and gustation impairments, cerebrovascular disorders, epileptic seizures, and myalgia were detected as other findings apart from the headache It is suggested that determining these neurological symptoms prevents the diagnosis delay and helps to prohibit virus spread

Guillain-Barre syndrome during COVID-19 pandemic: an overview of the reports.

Abstract: Similar to severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), the coronavirus disease 2019 (COVID-19) has neurological symptoms. COVID-19 patients have such clinical symptoms as headache, vomiting, nausea, dizziness, myalgia, anosmia, ageusia, and disorder of consciousness. These symptoms confirm that the nervous system is involved in the COVID-19 infection. Guillain-Barre syndrome (GBS) is a heterogeneous disorder which often follows a viral infection. According to the assessment case reports from the beginning of the COVID-19 infection so far, it is possible that GBS is linked to the COVID-19 infection. It seems that paying attention to the neurological effects of COVID-19 is necessary.

New clinical manifestation of COVID-19 related Guillain-Barrè syndrome highly responsive to intravenous immunoglobulins: two Italian cases.

Abstract: The above article was published online with inverted given and family names. The correct presentation has been corrected above.

HLA and immunological features of SARS-CoV-2-induced Guillain-Barré syndrome

Abstract: We report the clinical and immunological features in a case of SARS-CoV-2-induced Guillain-Barre syndrome (Si-GBS), suggesting that (1) Si-GBS can develop even after paucisymptomatic COVID-19 infection; (2) a distinctive cytokine repertoire is associated with this autoimmune complication, with increased CSF concentration of IL-8, and moderately increased serum levels of IL-6, IL-8, and TNF-α; (3) a particular genetic predisposition can be relevant, since the patient carried several HLA alleles known to be associated with GBS, including distinctive class I (HLA-A33) and class II alleles (DRB1*03:01 and DQB1*05:01). To the best of our knowledge, this is the first case of GBS in which SARS-CoV-2 antibodies were detected in the CSF, further strengthening the role of the virus as a trigger. In conclusion, our study suggests that SARS-CoV-2 antibodies need to be searched in the serum and CSF in patients with GBS living in endemic areas, even in the absence of a clinically severe COVID-19 infection, and that IL-8 pathway can be relevant in Si-GBS pathogenesis. Further studies are needed to conclude on the relevance of the genetic findings, but it is likely that HLA plays a role in this setting as in other autoimmune neurological syndromes, including those triggered by infections.

Potential neurological impact of coronaviruses: implications for the novel SARS-CoV-2.

Abstract: Coronaviruses (CoV) are viruses widely known to cause severe respiratory distress due to the prominent clinical symptoms presented. These symptoms, which include fever and dry cough, are frequently found in individuals with CoV infection. Neurological manifestations of CoV have often been neglected; however, recent studies have reported neurological consequences of CoV infection. Here, we review these literatures and discuss the neurologic impact of CoV while highlighting potential implications of the novel SARS-CoV-2 in the nervous system. We also discuss the possible routes by which these viruses invade the nervous system and the mechanism by which they may induce neurological damage.

Neurological diseases as mortality predictive factors for patients with COVID-19: a retrospective cohort study.

Abstract: In the current study, we evaluated factors that increase the coronavirus disease (COVID-19) patient death rate by analyzing the data from two cohort hospitals. In addition, we studied whether underlying neurological diseases are risk factors for death. In this retrospective cohort study, we included 103 adult inpatients (aged ≥ 18 years). We evaluated differences in demographic data between surviving and non-surviving COVID-19 patients. In a multivariate logistic analysis, age and the presence of chronic lung disease and Alzheimer’s dementia (AD) were the only significant parameters for predicting COVID-19 non-survival (p < 0.05). However, hypertension, coronary vascular disease, dyslipidemia, chronic kidney disease, diabetes, and history of taking angiotensin II receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors, as well as nonsteroidal anti-inflammatory drugs (NSAIDs), were not significantly associated with the death of COVID-19 patients. The optimal cutoff value obtained from the maximum Youden index was 70 (sensitivity, 80.77%; specificity, 61.04%), and the odds ratio of non-survival increased 1.055 fold for every year of age. Clinicians should closely monitor and manage the symptoms of COVID-19 patients who are over the age of 70 years or have chronic lung disease or AD.

Early neurological manifestations of hospitalized COVID-19 patients.

Abstract: Neurological manifestations can occur during coronavirus disease 19 (COVID-19) Several pathogenic mechanisms have been hypothesized, without conclusive results In this study, we evaluated the most frequent neurological symptoms in a cohort of hospitalized COVID-19 patients, and also investigated the possible relationship between plasmatic inflammatory indices and olfactory disorders (ODs) and between muscle pain and creatine kinase (CK) We consecutively enrolled hospitalized COVID-19 patients A structured questionnaire concerning typical and neurological symptoms, focusing on headache, dizziness, ODs, taste disorders (TDs), and muscle pain, was administrated by telephone interviews Common neurological symptoms were reported in the early phase of the disease, with a median onset ranging from 1 to 3 days Headache showed tension-type features and was more frequently associated with a history of headache Patients with ODs less frequently needed oxygen therapy Inflammatory indices did not significantly differ between patients with and without ODs Muscle pain did not show any association with CK level but was more frequently associated with arthralgia and headache In our cohort, ODs were an early symptom of COVID-19, more frequently reported by patients with milder forms of disease Headache in association with arthralgia and muscle pain seems to reflect the common symptoms of the flu-like syndrome, and not COVID-19 infection-specific

Challenges and management of neurological and psychiatric manifestations in SARS-CoV-2 (COVID-19) patients.

Abstract: COVID-19 is a pandemic caused by human coronavirus (HCoV) SARS-CoV-2, which originated in Wuhan, China, at the end of 2019 and spread globally during 2020. Due to the difficulty of clinical decision-making during this period, our study group reviewed current literature focusing on the neurological and psychiatric aspects of COVID-19. Despite the knowledge on this newly discovered virus which is constantly evolving, different pieces of evidence reported an association between COVID-19 and neurological symptoms like headache, dizziness, taste and smell disorders and complications involving the nervous system eventually triggered by the pathologic processes elicited by SARS-CoV-2. It seems that younger patients are less prone to develop severe forms of COVID-19. However, neurological signs have been reported in paediatric patients as well, and in some cases, the infection presented neurological sequelae. Furthermore, children with particular neurological diseases or treated with specific drugs (e.g. immune-suppressant therapies) must be carefully monitored during this pandemic. Neurologists should be aware of the main drug-drug interactions and the neurological side effects of COVID-19 treatments. Notably, adverse mental health impact has been reported in patients with SARS-CoV-2, which could be related either to the social strain or to the eventual neurotropic effects of the virus, which in other infections have been proven to promote the onset of psychiatric symptoms. Further, psychiatric population may be more vulnerable to the infection and at higher risk for adverse outcomes.

Assessing disability and relapses in multiple sclerosis on tele-neurology.

Abstract: As a consequence of the coronavirus disease 2019 (COVID-19) pandemic, a large amount of consultations will be delivered through tele-medicine, especially for diseases causing chronic disability and requiring immunomodulatory treatments, such as multiple sclerosis (MS). We have hereby reviewed available tools for tele-neurology examination in MS, including components of neurological examination that can be assessed through video, patient-reported outcome measures (PROMs), and digital technology. Overall, we have suggested a battery for assessing MS disability and relapses on tele-medicine, which brings together conventional examination, PROMs (e.g., Patient Determined Disease Steps, MS Impact Scale), and cognitive tests (Symbol Digit Modalities Test) that can be delivered remotely and in multiple languages. The use of common tools for neurological examination could improve tele-neurology practice for both general neurologists and MS specialists, and quality of care for people with MS.

West syndrome: a comprehensive review

Abstract: Since its first clinical description (on his son) by William James West (1793–1848) in 1841, and the definition of the classical triad of (1) infantile spasms; (2) hypsarrhythmia, and (3) developmental arrest or regression as “West syndrome”, new and relevant advances have been recorded in this uncommon disorder. New approaches include terminology of clinical spasms (e.g., infantile (IS) vs. epileptic spasms (ES)), variety of clinical and electroencephalographic (EEG) features (e.g., typical ictal phenomena without EEG abnormalities), burden of developmental delay, spectrum of associated genetic abnormalities, pathogenesis, treatment options, and related outcome and prognosis. Aside the classical manifestations, IS or ES may present with atypical electroclinical phenotypes (e.g., subtle spasms; modified hypsarrhythmia) and may have their onset outside infancy. An increasing number of genes, proteins, and signaling pathways play crucial roles in the pathogenesis. This condition is currently regarded as a spectrum of disorders: the so-called infantile spasm syndrome (ISs), in association with other causal factors, including structural, infectious, metabolic, syndromic, and immunologic events, all acting on a genetic predisposing background. Hormonal therapy and ketogenic diet are widely used also in combination with (classical and recent) pharmacological drugs. Biologically targeted and gene therapies are increasingly studied. The present narrative review searched in seven electronic databases (primary MeSH terms/keywords included West syndrome, infantile spasms and infantile spasms syndrome and were coupled to 25 secondary clinical, EEG, therapeutic, outcomes, and associated conditions terms) including MEDLINE, Embase, Cochrane Central, Web of Sciences, Pubmed, Scopus, and OMIM to highlight the past knowledge and more recent advances.

Self-reported needs of patients with Parkinson's disease during COVID-19 emergency in Italy.

Abstract: Because of COVID-19 outbreak, regular clinical services for Parkinson's disease (PD) patients have been suddenly suspended, causing worries, confusion and unexpected needs in such frail population. Here, we reviewed the messages spontaneously sent by patients to an Italian PD clinic during the first two weeks of COVID-19 lockdown (9-21 March 2020), in order to highlight their main needs and then outline appropriate strategies of care for this critical period. One hundred sixty-two messages were analysed. Forty-six percent queried about clinical services; 28% communicated an acute clinical worsening for which a therapeutic change was done in 52% of cases; 17% (those patients with younger age and milder disease) asked about the relationship between PD and COVID-19; 8% informed about an intercurrent event. Our analysis suggests that PD patients' needs during COVID-19 emergency include appropriate and complete information, a timely update on changes in clinical services, and the continuity of care, even in a remote mode. By addressing these issues, acute clinical worsening, complications and subsequent therapeutic changes could be prevented. In this perspective, telecommunication systems and virtual medicine should be implemented.

Seizure in patients with COVID-19.

Abstract: The purpose of the current study was to collect the data on the occurrence of seizures in patients with COVID-19 and to clarify the circumstances of the occurrence of seizures in these patients. All consecutive patients who referred to healthcare facilities anywhere in Fars province (located in South Iran with a population of 4.851 million people) from February 19 until June 2, 2020, and had confirmed COVID-19 by positive result on polymerase chain reaction testing and seizure were included. During the study period, 6,147 people had confirmed COVID-19 in Fars province, Iran; 110 people died from the illness (case fatality rate 1.79%). During this time period, five people had seizures (seizure rate 0.08%). In four patients, seizure was one of the presenting manifestations, and in one person, it happened during the course of hospital admission. Two patients had status epilepticus. All patients experienced hypoxemia and four of them needed respirator. Two patients had related metabolic derangements and one had cerebrospinal fluid (CSF) lymphocytic pleocytosis. Brain imaging was abnormal in three patients. Four patients died. New-onset seizures in critically ill patients with COVID-19 should be considered as acute symptomatic seizures and the treating physician should try to determine the etiology of the seizure and manage the cause immediately and appropriately. Detailed clinical, neurological, imaging, and electrophysiological investigations and attempts to isolate SARS-CoV-2 from CSF may clarify the role played by this virus in causing seizures in these patients.

The role of virtual reality on outcomes in rehabilitation of Parkinson's disease: meta-analysis and systematic review in 1031 participants

Abstract: Parkinson’s disease (PD) is managed primarily by dopamine agonists and physiotherapy while virtual reality (VR) has emerged recently as a complementary method. The present study reviewed the effectiveness of VR in rehabilitation of patients with PD. Literature search up to June 2019 identified ten studies (n = 343 participants) suitable for meta-analysis and 27 studies (n = 688 participants) for systematic review. Standard mean difference (SMD) and 95% confidence intervals (CI) were calculated using a random effects model. In meta-analysis, compared with active rehabilitation intervention, VR training led to greater improvement of stride length, SMD = 0.70 (95%CI = 0.32–1.08, p = 0.0003), and was as effective for gait speed, balance and co-ordination, cognitive function and mental health, quality of life and activities of daily living. Compared with passive rehabilitation intervention, VR had greater effects on balance: SMD = 1.02 (95%CI = 0.38–1.65, p = 0.002). Results from single randomised controlled trials showed that VR training was better than passive rehabilitation intervention for improving gait speed SMD = 1.43 (95%CI = 0.51–2.34, p = 0.002), stride length SMD = 1.27 (95%CI = 0.38–2.16, p = 0.005) and activities of daily living SMD = 0.96 (95%CI = 0.02–1.89). Systematic review showed that VR training significantly (p < 0.05) improved motor function, balance and co-ordination, cognitive function and mental health, and quality of life and activities of daily living. VR used in rehabilitation for patients with PD improves a number of outcomes and may be considered for routine use in rehabilitation.

Brainstem involvement and respiratory failure in COVID-19.

Abstract: Respiratory failure is the most worrisome problem of COVID-19. Patients may develop severe pneumonia requiring invasive mechanical ventilation and a significant proportion of them dies. It has been suggested that brainstem might play a role in severe respiratory failure of COVID-19 patients. We described three COVID-19 patients in ICU at Federico II Hospital in Naples that, although had recovered from pneumonia, could not be weaned from invasive mechanical ventilation. Our clinical evaluation was consistent with an involvement of the brainstem and especially of respiratory centre thus possibly explaining the weaning failure in patients that were awake and had recovered from lung involvement. Our data, though limited, indicate that brainstem involvement may play a role in respiratory failure and perhaps in the high death rate of COVID-19 patients. Moreover, the weaning failure from mechanical ventilation due to central respiratory drive depression might underlie the unusual long stay in ICU reported for COVID-19 patients.

An Italian multicenter retrospective-prospective observational study on neurological manifestations of COVID-19 (NEUROCOVID).

Abstract: Neurological manifestations of COVID-19 have been described in both single case reports and retrospective scanty case series. They may be linked to the potential neurotropism of the SARS-COV-2 virus, as previously demonstrated for other coronaviruses. We report here the description of a multicenter retrospective-prospective observational study promoted by the Italian Society of Neurology (SIN), involving the Italian Neurological Departments, who will consecutively recruit patients with neurological symptoms and/or signs, occurred at the onset or as a complication of COVID-19. Hospitalized patients will be recruited either in neurological wards or in COVID wards; in the latter cases, they will be referred from other specialists to participant neurologists. Outpatients with clinical signs of COVID and neurological manifestations will be also referred to participating neurologists from primary care physicians. A comprehensive data collection, in the form of electronic case report form (eCRF), will register all possible neurological manifestations involving central nervous systems, peripheral nerves, and muscles, together with clinical, laboratory (including cerebrospinal fluid, if available), imaging, neurological, neurophysiological, and neuropsychological data. A follow-up at hospital discharge (in hospitalized patients), and for all patients after 3 and 6 months, is also planned. We believe that this study may help to intercept the full spectrum of neurological manifestations of COVID-19 and, given the large diffusion at national level, can provide a large cohort of patients available for future more focused investigations. Similar observational studies might also be proposed at international level to better define the neurological involvement of COVID-19.

Quantitative metabolomics of saliva using proton NMR spectroscopy in patients with Parkinson’s disease and healthy controls

Abstract: Parkinson’s disease (PD) is a multisystem disorder of unknown etiology, highlights a broad array of symptoms and pathological features influencing organs throughout the body. The metabolic profile of saliva in patients with PD may be influenced by malabsorption in the gastroenteric tract, neurodegeneration, and mitochondrial dysfunction. In the present study, we apply a powerful NMR metabolomics approach for biomarker identification in PD using saliva, a non-invasive bio-fluid. Metabolic profiling of saliva were studied in patients with PD (n = 76) and healthy controls (HC, n = 37) were analyzed and differentiated PD from HC. A total of 40 metabolites including aromatic amino acids, short-chain fatty acids, branched chain amino acids, taurine, and N-acetylglutamate were identified. Spectral binned data and concentration of metabolites were estimated for analysis. Increased concentration of phenylalanine, tyrosine, histidine, glycine, acetoacetate, taurine, TMAO, GABA, N-acetylglutamate, acetoin, acetate, alanine, fucose, propionate, isoleucine, and valine were observed in PD as compared to HC. Further, subgroup analysis among early PD, advanced PD, and HC groups, revealed increased metabolite concentration in early PD group as compared to advanced PD and HC group. Analysis revealed potential biomarkers and their involvement in amino acid metabolism, energy metabolism, neurotransmitters metabolism, and microflora system. Patients with early PD exhibited higher metabolite concentration as compared to advanced PD group which might be associated with dopaminergic treatment. The results of our data indicate that patients with PD might be characterized by metabolic imbalances like gut microflora system, energy metabolites, and neurotransmitters which may contribute to the PD pathogenesis.

Digital triage for people with multiple sclerosis in the age of COVID-19 pandemic.

Abstract: We propose a possible approach for the remote monitoring of infection risk in people with multiple sclerosis, especially those on immunosuppressant drugs, during COVID-19 pandemic. We developed a digital triage tool to be sent to patients to quickly identify people with high risk of COVID-19 infection. This tool will also limit unnecessary accesses to the MS centers reducing the risk of spreading the infection.

Real-time assessment of COVID-19 prevalence among multiple sclerosis patients: a multicenter European study.

Abstract: We assessed the prevalence and impact of COVID-19 among multiple sclerosis (MS) patients across Europe by leveraging participant data collected as part of the ongoing EU IMI2 RADAR-CNS major programme aimed at finding new ways of monitoring neurological disorders using wearable devices and smartphone technology In the present study, 399 patients of RADAR-MS have been included (mean age 439 years, 607% females) with 87/399 patients (218%) reporting major symptoms suggestive of COVID-19 A trend for an increased risk of COVID-19 symptoms under alemtuzumab and cladribine treatments in comparison to injectables was observed Remote monitoring technologies may support health authorities in monitoring and containing the ongoing pandemic

Impact of quarantine due to COVID infection on migraine: a survey in Genova, Italy.

Abstract: Quarantine is a well-known risk factor for psychological and psychiatric disturbances. We evaluated burden of migraine during lockdown due to COVID 19 pandemia. Forty-nine subjects followed in our headache clinic for migraine were evaluated for migraine burden by means of global assessment of migraine severity (GAMS) and visual analogue scale (VAS) by phone interview. Moreover, depression and anxiety were quantified by Beck depression inventory (BDI) and Zung Self-Rating Anxiety Scale (SAS). We evaluated changes in the value of migraine score from the 2 months immediately before lockdown (from January 1 to March 9) to the 2 months of quarantine (from March 10 to May 3). Value of GAMS was 5.61 ± 0.76 before and 4.16 ± 1.46 during quarantine (p < .001). VAS was 7.49 ± 1.10 before and 5.47 ± 1.88 during quarantine (p < .001). We also found a time by depression level interaction, F(1,47) = 6.21, p = .016, F(1,47) = 14.52, p < .006, respectively, showing that subjects with lower level of depression had better course of migraine. In conclusion, we showed that, during quarantine due to COVID pandemia, subjects with migraine had fewer migraine attacks and lesser pain and show moderate level of depression, correlated to migraine burden.

No lockdown for neurological diseases during COVID19 pandemic infection.

Abstract: Twenty-twenty will be remembered as the year that brought new and unprecedented challenges to the healthcare system worldwide due to the Covid-19 pandemic. Currently, onethird of the world population is living in a coronavirus “lockdown modus” as part of the world’s most massive and restrictive mass quarantine. The first epidemic of cases with unexplained low respiratory infections detected in Wuhan, the largest metropolitan area in China’s Hubei province, was first reported to the WHO Country Office in China on December 31st, 2019 [1] In a meeting on January 30th, 2020, per the International Health Regulations (IHR, 2005), the outbreak was declared by the WHO a Public Health Emergency of International Concern (PHEIC) as it had spread to 18 countries with four countries reporting human-to-human transmission. WHO Director-General’s statement on the IHR Emergency Committee on Novel Coronavirus (2019-nCoV) [2]. Subsequently, the task of experts of the International Committee on Taxonomy of Viruses (ICTV) termed it the SARS-CoV-2 virus as it is very similar to the one that caused the SARS outbreak (SARS-CoVs). On February 11th, 2020, the WHO Director-General, Dr. Tedros Adhanom Ghebreyesus, announced that the disease caused by this new CoV was a “COVID-19,” which is the acronym of “coronavirus disease 2019” [2]. The potential for these viruses to grow and to become a pandemic worldwide seems to be a serious public health risk. Concerning COVID-19, the WHO raised the threat to the CoV epidemic to the “very high” level, on February 28th, 2020. On March 11th, as the number of COVID-19 cases outside China has increased 13 times and the number of countries involved has tripled with more than 118,000 cases in 114 countries, and over 4000 deaths, WHO declared the COVID-19 a pandemic [3]. Since the first case diagnosed on February 20th, 2020, in the Codogno Hospital (Lodi, Lombardy, Italy) [4], the infection has rapidly spread throughout Lombardy and the peninsula, reaching 97.689 confirmed cases, with 10.779 deaths as of March 29th, 2020. In Italy, in geographic regions of the north, initially, and subsequently throughout the country, political and health authorities are making incredible efforts to contain a shock wave that is severely testing the health system [5]. Therefore, the attention of healthcare providers is primarily focused on infected patients and the frontline responders. Nonetheless, the healthcare system needs to continue to respond to the needs of patients affected by noncommunicable diseases [6], which are the majority of conditions. In this regard, neurological disorders contribute to 11,6% of global DALYs and 16,5% of deaths from all causes, remaining the leading group cause of DALYs and the second leading group cause of deaths in the world [7]. Preparedness to continue to guarantee treatment to neurological patients is vital in containing and mitigating the collateral effects of COVID-19, which, based on current knowledge, does not seem to be a neurotropic virus and is reported to cause limited neurologic involvements [8]. Baracchini et al., in this brief report published in this current issue, are sharing how the University Hospital of Padua, with a catchment area of about 950.000 people, structured a pathway for acute stroke patients before admitting them to our Stroke Unit [9]. Since the outbreak of the COVID epidemic, a dedicated stroke triage protocol has been activated. The stroke patient who is already known to be COVID-19 positive undergoes Cerebral CT, CTA, and CTP on a high-performance mobile CT outside the Emergency Department. In the case of ischemic stroke without large vessel occlusion, the patient is transferred to the Infectious Disease Department or a dedicated Medical Department after thrombolysis treatment and will * Antonio Federico antonio.federico@unisi.it

Gender-related differences in migraine.

Abstract: Migraine is considered mostly a woman's complaint, even if it affects also men. Epidemiological data show a higher incidence of the disease in women, starting from puberty throughout life. The sex-related differences of migraine hold clinical relevance too. The frequency, duration, and disability of attacks tend to be higher in women. Because of this, probably, they also consult specialists more frequently and take more prescription drugs than men. Different mechanisms have been evaluated to explain these differences. Hormonal milieu and its modulation of neuronal and vascular reactivity is probably one of the most important aspects. Estrogens and progesterone regulate a host of biological functions through two mechanisms: nongenomic and genomic. They influence several neuromediators and neurotransmitters, and they may cause functional and structural differences in several brain regions, involved in migraine pathogenesis. In addition to their central action, sex hormones exert rapid modulation of vascular tone. The resulting specific sex phenotype should be considered during clinical management and experimental studies.

Dysphagia in neurological diseases: a literature review

Abstract: Dysphagia is defined as an impairment of this complex and integrated sensorimotor system. It is estimated that 400,000 to 800,000 individuals worldwide develop neurogenic dysphagia per year. Neurogenic dysphagia is typically occurring in patients with neurological disease of different etiologies. A correct and early diagnosis and an appropriate management of dysphagia could be useful for improving patient’s quality of life and may help to prevent or delay death. In the present review, we discuss thoroughly the anatomy and physiology of swallowing and also the pathophysiological mechanisms involved in impaired swallowing, as well as the diagnosis, management, and potential treatments of neurogenic dysphagia. Assessment of neurogenic dysphagia includes medical history, physical exam, and instrumental examinations (fiberoptic endoscopic evaluation of swallowing, videofluoroscopic swallowing study, electromyography). Pharmacological treatment of these problems includes oral anticholinergic drugs. Surgical myotomy of the cricopharyngeal muscle showed an important improvement of oropharyngeal dysphagia associated to upper esophageal sphincter hyperactivity. Chemical myotomy of the upper esophageal sphincter by local injections of botulinum toxin type A into the cricopharyngeal muscle has been proposed as an alternative less invasive and less unsafe than surgical myotomy.

Management of COVID-19 in people with epilepsy: drug considerations.

Abstract: People with epilepsy (PWE) are neither more likely to be infected by the coronavirus nor are they more likely to have severe COVID-19 manifestations because they suffer from epilepsy However, management of COVID-19 in PWE may be more complicated than that in other individuals Drug-drug interactions could pose significant challenges and cardiac, hepatic, or renal problems, which may happen in patients with severe COVID-19, may require adjustment to antiepileptic drugs (AEDs) In this review, we first summarize the potential drug-drug interactions between AEDs and drugs currently used in the management of COVID-19 We then summarize other challenging issues that may happen in PWE, who have COVID-19 and are receiving treatment