Showing papers in "Neurological Sciences in 2021"

Spectrum of neurological complications following COVID-19 vaccination.

Abstract: COVID-19 vaccines have brought us a ray of hope to effectively fight against deadly pandemic of COVID-19 and hope to save lives. Many vaccines have been granted emergency use authorizations by many countries. Post-authorization, a wide spectrum of neurological complications is continuously being reported following COVID-19 vaccination. Neurological adverse events following vaccination are generally mild and transient, like fever and chills, headache, fatigue, myalgia and arthralgia, or local injection site effects like swelling, redness, or pain. The most devastating neurological post-vaccination complication is cerebral venous sinus thrombosis. Cerebral venous sinus is frequently reported in females of childbearing age, generally following adenovector-based vaccination. Another major neurological complication of concern is Bell's palsy that was reported dominantly following mRNA vaccine administration. Acute transverse myelitis, acute disseminated encephalomyelitis, and acute demyelinating polyneuropathy are other unexpected neurological adverse events that occur as result of phenomenon of molecular mimicry. Reactivation of herpes zoster in many persons, following administration of mRNA vaccines, has been also recorded. Considering the enormity of recent COVID-19-vaccinated population, the number of serious neurological events is miniscule. Large collaborative prospective studies are needed to prove or disprove causal association between vaccine and neurological adverse events occurring vaccination.

Long-term neurological manifestations of COVID-19: prevalence and predictive factors.

Abstract: Clinical investigations have argued for long-term neurological manifestations in both hospitalised and non-hospitalised COVID-19 patients. It is unclear whether long-term neurological symptoms and features depend on COVID-19 severity. From a sample of 208 consecutive non-neurological patients hospitalised for COVID-19 disease, 165 survivors were re-assessed at 6 months according to a structured standardised clinical protocol. Prevalence and predictors of long-term neurological manifestations were evaluated using multivariate logistic regression analyses. At 6-month follow-up after hospitalisation due to COVID-19 disease, patients displayed a wide array of symptoms; fatigue (34%), memory/attention (31%) and sleep disorders (30%) were the most frequent. At neurological examination, 40% of patients exhibited neurological abnormalities, such as hyposmia (18.0%), cognitive deficits (17.5%), postural tremor (13.8%) and subtle motor/sensory deficits (7.6%). Older age, premorbid comorbidities and severity of COVID-19 were independent predictors of neurological manifestations in logistic regression analyses. Premorbid vulnerability and severity of SARS-CoV-2 infection impact on prevalence and severity of long-term neurological manifestations.

COVID-19, de novo seizures, and epilepsy: a systematic review.

Abstract: We discuss the evidence on the occurrence of de novo seizures in patients with COVID-19, the consequences of this catastrophic disease in people with epilepsy (PWE), and the electroencephalographic (EEG) findings in patients with COVID-19. This systematic review was prepared according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. MEDLINE, Scopus, and Embase from inception to August 15, 2020 were systematically searched. These key words were used: “COVID” AND “seizure” OR “epilepsy” OR “EEG” OR “status epilepticus” OR “electroencephalography”. We could identify 62 related manuscripts. Many studies were case reports or case series of patients with COVID-19 and seizures. PWE showed more psychological distress than healthy controls. Many cases with new-onset focal seizures, serial seizures, and status epilepticus have been reported in the literature. EEG studies have been significantly ignored and underused globally. Many PWE perceived significant disruption in the quality of care to them, and some people reported increase in their seizure frequency since the onset of the pandemic. Telemedicine is a helpful technology that may improve access to the needed care for PWE in these difficult times. De novo seizures may occur in people with COVID-19 and they may happen in a variety of forms. In addition to prolonged EEG monitoring, performing a through metabolic investigation, electrocardiogram, brain imaging, and a careful review of all medications are necessary steps. The susceptibility of PWE to contracting COVID-19 should be investigated further.

Intracranial hemorrhage in coronavirus disease 2019 (COVID-19) patients.

Abstract: Emerging evidence suggests that a subset of coronavirus disease 2019 (COVID-19) patients may present with or develop cerebrovascular disease during the course of hospitalization. Whereas ischemic stroke in COVID-19 patients has been well described, data on intracranial hemorrhage (ICH) in these patients is still limited. We, therefore, conducted a rapid systematic review of current scientific literature to identify and consolidate evidence of ICH in COVID-19 patients. A systematic search of literature was conducted between November 1, 2019, and August 14, 2020, on PubMed and China National Knowledge Infrastructure (CNKI) to identify eligible studies. A total of 23 studies describing ICH in 148 COVID-19 patients were included. The pooled incidence of ICH in COVID-19 patients was 0.7% (95% CI 0.5–0.9), with low levels of inter-study heterogeneity observed (I2 = 33.6%, Cochran’s Q = 12.05, p = 0.149). Most of the patients were elderly male patients (65.8%) with comorbidities, the most common being systemic hypertension (54%). Hemorrhage involving multiple cranial compartments was reported in 9.5% of cases. Single compartments were involved in the rest, with intraparenchymal hemorrhage (IPH) being the most common variety (62.6%) and intraventricular hemorrhage (IVH) the least common (1.4%). Half of these patients were on some form of anticoagulation. Overall, the mortality rate in the COVID-19 patients with ICH was about 48.6%. Although relatively uncommon among COVID-19 patients, ICH is associated with a high mortality rate. Early identification of patients at risk of developing ICH, particularly with comorbid conditions and on anticoagulant therapy, may be important to improve outcomes.

Neuropathologic findings of patients with COVID-19: a systematic review.

Abstract: Despite the expanding literature that discusses insights into the clinical picture and mechanisms by which the SARS-CoV-2 virus invades the nervous system, data on the neuropathologic findings of patients who died following SARS-CoV-2 infection is limited. A broad literature search was done for published articles that reported on histopathological findings of the brain in patients with COVID-19 in PubMed by MEDLINE, Embase, CENTRAL by the Cochrane Library, and SCOPUS from December 31, 2019 to October 31, 2020. The systematic literature search strategy used resulted in a total of 1608 articles of which 14 were included in the analysis (PROSPERO registration number: CRD42020221022). There were ten case series, two case reports, one retrospective cohort, and one prospective cohort. The age of the patients ranged between 38 and 90 years old, most of them older than 65 years old (n=66, 45.2%) and males (n=79, 54.1%). Most tested negative in SARS-CoV-2 immunohistochemistry (n=70, 47.9%). The striking pathologic changes included diffuse edema (n=25, 17.1%), gliosis with diffuse activation of microglia and astrocytes (n=52, 35.6%), infarctions involving cortical and subcortical areas of the brain (n=4, 2.7%), intracranial bleed (subarachnoid hemorrhage and punctate hemorrhages) (n=18, 12.4%), arteriosclerosis (n=43, 29.5%), hypoxic-ischemic injury (n=41, 28.1%), and signs of inflammation (n=52, 35.6%). The cause of death was attributed to the cardiorespiratory system (n=66, 45.2%). The neuropathologic changes observed likely represent direct cytopathic effects and indirect effects secondary to host-specific inflammatory response induced by the viral infection. Further studies however are required to better elucidate the pathologic mechanism.

Physical exercise effects on the brain during COVID-19 pandemic: links between mental and cardiovascular health.

Abstract: The current pandemic was caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The quarantine period during corona virus disease 19 (COVID-19) outbreak might affect the quality of life leading thousands of individuals to diminish the daily caloric expenditure and mobility, leading to a sedentary behavior and increase the number of health disorders. Exercising is used as a non-pharmacological treatment in many chronic diseases. Here, we review the molecular mechanisms of physical exercise in COVID-19 pandemic on mental health. We also point links between exercise, mental, and cardiovascular health. The infection caused by SARS-CoV-2 affects host cells binding to angiotensin-converting enzyme-2 (ACE2), which is the receptor for SARS-CoV-2. If there is not enough oxygen supply the lungs and other tissues, such as the heart or brain, are affected. SARS-CoV-2 enhances ACE2 leading to inflammation and neuronal death with possible development of mood disorders, such as depression and anxiety. Physical exercise also enhances the ACE2 expression. Conversely, the activation of ACE2/Ang 1-7/Mas axis by physical exercise induces an antiinflammatory and antifibrotic effect. Physical exercise has beneficial effects on mental health enhancing IGF-1, PI3K, BDNF, ERK, and reducing GSK3β levels. In addition, physical exercise enhances the activity of PGC-1α/ FNDC5/Irisin pathway leading to neuronal survival and the maintenance of a good mental health. Thus, SARS-CoV-2 infection leads to elevation of ACE2 levels through pathological mechanisms that lead to neurological and cardiovascular complications, while the physiological response of ACE2 to physical exercise improves cardiovascular and mental health.

Direct and indirect neurological, cognitive, and behavioral effects of COVID-19 on the healthy elderly, mild-cognitive-impairment, and Alzheimer's disease populations.

Abstract: Healthy elderly, mild cognitive impairment and Alzheimer’s disease populations have been among the most affected in the early stages of the COVID-19 pandemic due to the direct effects of the virus, and numerous indirect effects now emerge and will have to be carefully assessed over time. This article reviews the main articles that have been published so far about the direct and indirect effects of the COVID-19 pandemic on these particularly fragile populations. The pandemic associated to COVID-19 has shifted most of the health resources to the emergency area and has consequently left the three main medical areas dealing with the elderly population (oncology, time-dependent diseases and degenerative disease) temporarily “uncovered”. In the phase following the emergency, it will be crucial to guarantee to each area the economic and organizational resources to quickly return to the level of support of the prepandemic state. The emergency phase represented a significant occasion of discussion on the possibilities of telemedicine which will inevitably become increasingly important, but all the limits of its use in the elderly population have to be considered. In the post-lockdown recovery phase, alongside the classic medical evaluation, the psychological evaluation must become even more important for doctors caring about people with cognitive decline as well as with their caregivers.

Watch out for neuromyelitis optica spectrum disorder after inactivated virus vaccination for COVID-19.

Abstract: With recent availability of COVID-19 vaccine, post-vaccination neurological complications had been occasionally reported. Here, we reported for the first time a case of neuromyelitis optica spectrum disorder (NMOSD) that developed after the first dose of inactivated virus vaccine for COVID-19. The patient developed mild fever, vomiting, diarrhea, and cough after receiving the first dose of inactivated virus vaccine. Two months later, she experienced dizziness and unsteady walking. MRI scanning of the brain revealed lesions in area postrema and bilateral hypothalamus, typical for NMOSD. Serum antibodies for AQP4, ANA, SSA, SSB, Ro-52, and p-ANCA were positive. The patient was diagnosed as AQP4-positive NMOSD with coexisting systemic autoimmunity. After treatment with methylprednisolone (500 mg for 5 days), symptoms were greatly relieved. As NMOSD is seriously harmful and curative, it is important to be aware of the NMOSD symptoms after vaccination. Cautions should be given for those with preexisting systemic autoimmune abnormalities in vaccination for COVID-19.

A case of acute demyelinating polyradiculoneuropathy with bilateral facial palsy after ChAdOx1 nCoV-19 vaccine.

Abstract: The coronavirus disease 2019 (COVID-19) global pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), began in late 2019. Researchers around the world are aggressively working to develop a vaccine. One of the vaccines approved against COVID-19 is Oxford–AstraZeneca chimpanzee adenovirus vectored vaccine ChAdOx1 nCoV-19. We described a patient who developed four limb distal paraesthesia, postural instability, and facial diplegia, ten days after vaccination with ChAdOx1 nCoV-19 (ABW1277). The electrophysiological findings were compatible with acute demyelinating motor polyneuropathy (Guillain-Barre syndrome). We therefore want to describe a temporal correlation between administration of ChAdOx1 nCoV-19 (ABW1277) vaccine and GBS without evidence of other predisposing infectious or autoimmune factors. This paper aims to highlight the importance of pharmacovigilance and subsequent reports will be needed to evaluate the possible correlation between these two events.

Is Guillain-Barrè syndrome triggered by SARS-CoV-2? Case report and literature review.

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the infectious agent responsible for coronavirus disease 2019 (COVID-19). Respiratory and gastrointestinal manifestations of SARS-CoV-2 are well described, less defined is the clinical neurological spectrum of COVID-19. We reported a case of COVID-19 patient with acute monophasic Guillain-Barre syndrome (GBS), and a literature review on the SARS-CoV-2 and GBS etiological correlation. A 68 years-old man presented to the emergency department with symptoms of acute progressive symmetric ascending flaccid tetraparesis. Oropharyngeal swab for SARS-CoV-2 tested positive. Neurological examination showed bifacial nerve palsy and distal muscular weakness of lower limbs. The cerebrospinal fluid assessment showed an albuminocytologic dissociation. Electrophysiological studies showed delayed distal latencies and absent F waves in early course. A diagnosis of Acute Inflammatory Demyelinating Polyradiculoneuropathy (AIDP) subtype of GBS was then made. Neurological manifestations of COVID-19 are still under study. The case we described of GBS in COVID-19 patient adds to those already reported in the literature, in support of SARS-CoV-2 triggers GBS. COVID-19 associated neurological clinic should probably be seen not as a corollary of classic respiratory and gastrointestinal symptoms, but as SARS-CoV-2-related standalone clinical entities. To date, it is essential for all Specialists, clinicians and surgeons, to direct attention towards the study of this virus, to better clarify the spectrum of its neurological manifestations.

Telemedicine for management of patients with amyotrophic lateral sclerosis through COVID-19 tail.

Abstract: Over the last months, due to coronavirus disease (COVID-19) pandemic, containment measures have led to important social restriction. Healthcare systems have faced a complete rearrangement of resources and spaces, with the creation of wards devoted to COVID-19 patients. In this context, patients affected by chronic neurological diseases, such as amyotrophic lateral sclerosis (ALS), are at risk to be lost at follow-up, leading to a higher risk of morbidity and mortality. Telemedicine may allow meet the needs of these patients. In this commentary, we briefly discuss the digital tools to remotely monitor and manage ALS patients. Focusing on detecting disease progression and preventing life-threatening conditions, we propose a toolset able to improve ALS management during this unprecedented situation.

Facing the digital divide into a dementia clinic during COVID-19 pandemic: caregiver age matters.

Abstract: The coronavirus disease 2019 (COVID-19) pandemic has dramatically stressed the health care system and has provoked changes in population use of digital technologies. Digital divide is any uneven distribution in Information and Communications Technologies between people. The purpose of this work was to describe the digital divide of a population of patients with dementia contacted by telemedicine during Italian lockdown for COVID-19 pandemic. One hundred eight patients with cognitive impairment were contacted by video call to perform a telemedicine neurological evaluation. Information on patients and caregivers attending the televisit were recorded. Seventy-four patients connected with neurologist (successful televisit, 68.5%) and 34 patients were not able to perform televisit and were contacted by phone (failed televisit, 31.5%). No significant differences were observed among the two groups concerning age, gender, and education, but the prevalence of successful televisit was higher in the presence of younger caregivers: televisits performed in the presence of subjects of younger generation (sons and grandsons) had a successful rate higher (86% successful, 14% failed) than the group without younger generation caregiver (49% successful, 51% failed). This difference is mainly due to the ability of technological use among younger people. The most impacting factors on digital divide in our population are the social support networks and the experience with the technology: the presence of a digital native caregiver. The COVID-19 pandemic is unmasking an emerging form of technology-related social inequalities: political and community interventions are needed to support the most socially vulnerable population and prevent social health inequalities.

Early outcomes of migraine after erenumab discontinuation: data from a real-life setting.

Abstract: Monoclonal antibodies targeting the calcitonin gene-related peptide, including erenumab, are migraine-specific preventive treatments, whose long-term effectiveness has still to be evaluated in real-life settings. We assessed early outcomes of erenumab discontinuation after a 52-week treatment in patients with a continuous positive response to the drug. We evaluated the early outcomes after treatment completion in migraineurs from a real-life multicenter register. All patients received monthly erenumab for 52 weeks and attended a 8-week follow-up after treatment completion. Primary outcomes were responder rates and changes in monthly migraine days (MMDs), acute medications days (AMDs), and pain intensity on a Numerical Rating Scale (NRS score) during weeks 1–4 after erenumab treatment completion. The 32 included patients reported a decrease in MMDs, AMDs, and NRS score during the last 4 weeks of treatment compared with baseline (P<0.001). During weeks 1–4 after treatment completion, all the outcome measures increased compared with the last 4 weeks of treatment (P < 0.001) despite staying lower than baseline (MMDs and AMDs P < 0.001, NRS score P = 0.005). Over the same time frame, 18 (56%) patients maintained a ≥ 50% reduction from baseline in MMDs. At week 4 after treatment completion, 10 (31%) patients restarted treatment due to disease rebound to baseline levels. More than half patients had an early disease worsening, while the remaining patients maintained their responder status during weeks 1–4 after treatment completion. Further studies might identify predictors of prolonged response to erenumab and define the optimal treatment duration according to patients’ characteristics.

New-onset refractory status epilepticus (NORSE) in post SARS-CoV-2 autoimmune encephalitis: a case report.

Abstract: The 2019 new coronavirus (SARS-CoV-2) is a novel respiratory virus which has increasingly spread all over the world. Although the predominant clinical presentation is represented by respiratory symptoms, neurological manifestation of SARS-CoV-2 is being increasingly recognized. In the present report, we present a case of post SARS-CoV-2 autoimmune encephalitis associated with a new-onset refractory status epilepticus (NORSE).

Qualitative smell/taste disorders as sequelae of acute COVID-19.

Abstract: Qualitative smell/taste disorders (such as phantosmia, parosmia, phantogeusia, and parageusia) have not yet been fully characterized in patients who had COVID-19, whereas quantitative disturbances (i.e., reduction/loss of smell/taste) have been widely investigated. To simultaneously assess the presence of both quantitative and qualitative smell/taste dysfunctions in patients who suffered from COVID-19. We enrolled 17 consecutive patients who suffered from COVID-19 over the last 6 months and 21 healthy controls, matched for sex and age. After a negative nasopharyngeal swab, the Sniffin’ Sticks Test and the Taste Strips were used to assess olfactory and taste function, respectively. At the same time, the presence of phantosmia, parosmia, phantogeusia, and parageusia was investigated with a standardized questionnaire. Qualitative disturbances of smell and/or taste were found in 6/17 (35.3%) patients. Phantosmia was reported in 2/17 (11.8%) patients and parosmia in 4/17 (23.5%). There were no significant differences in smell test scores between patients who reported phantosmia and/or parosmia and patients who did not. Phantogeusia was described in 3/17 (17.6%) patients, and parageusia was identified in 4/17 (23.5%) patients. All tested patients were normogeusic. Around one-third of patients who recover from COVID-19 may have persistent qualitative dysfunction in smell/taste domains. Detection of phantogeusia in long-term COVID-19 patients represents a further novel finding. Further investigation is needed to better characterize the pathophysiology of phantosmia, parosmia, phantogeusia, and parageusia in patients who had COVID-19.

Cumulative risk of stroke recurrence over the last 10 years: a systematic review and meta-analysis.

Abstract: Stroke is still the main cause of death and disability worldwide, numerous studies of recurrence risk have been reported, while systematic estimates of stroke recurrence risk in the last 10 years are variable. This review aims to estimate the cumulative stroke recurrence risk in the last 10 years for secondary prevention management in future. A systematic search from January 2009 to March 2019 was conducted through PubMed, EMBASE, Web of Science, Wan-fang, and CNKI. Search terms were in English and Chinese. A total of 37 studies involving 1,075,014 stroke patients were included. The pooled stroke recurrence rate was 7.7% at 3 months, 9.5% at 6 months, 10.4% at 1 year, 16.1% at 2 years, 16.7% at 3 years, 14.8% at 5 years, 12.9% at 10 years, and 39.7% at 12 years after the initial stroke. In addition, the pooled recurrence rate of 32 studies including stroke patients over 50 years only at seven time points except for subgroup of 10 years was 7.7%, 9.5%, 11.2%, 16.1%, 19.3%, 18.1%, and 39.7%, respectively. Meta-regression showed that the time points explained 23.02% of the variance among studies, while regions, age, and stroke types showed no significant contribution to heterogeneity. The risk of stroke recurrence varies greatly from 3 months to over 10 years and increases significantly over time in both young and old subgroup. The heterogeneity may be explained by follow-up time, regions, age, methodology differences, and stroke types, which was needed further exploration in future.

Impact of COVID-19 on stroke admissions, treatments, and outcomes at a comprehensive stroke centre in the United Kingdom.

Abstract: The coronavirus disease (COVID-19) pandemic has changed routine clinical practice worldwide with major impacts on the provision of care and treatment for stroke patients. This retrospective observational study included all patients admitted to the Royal Stoke University Hospital in Stoke-on-Trent, UK, with a stroke or transient ischaemic attack between March 15th and April 14th, 2020 (COVID). Patient demographics, characteristics of the stroke, treatment details and logistics were compared with patients admitted in the corresponding weeks in the year before (2019). There was a 39.5% (n = 101 vs n = 167) reduction in admissions in the COVID cohort compared with 2019 with more severe strokes (median National Institutes of Health Stroke Scale (NIHSS) 7 vs 4, p = 0.02), and fewer strokes with no visible acute pathology (21.8 vs 37.1%, p = 0.01) on computed tomography. There was no statistically significant difference in the rates of thrombolysis (10.9 vs 13.2%, p = 0.72) and/or thrombectomy (5.9 vs 4.8%, p = 0.90) and no statistically significant difference in time from stroke onset to arrival at hospital (734 vs 576 min, p = 0.34), door-to-needle time for thrombolysis (54 vs 64 min, p = 0.43) and door-to-thrombectomy time (181 vs 445 min, p = 0.72). Thirty-day mortality was not significantly higher in the COVID year (10.9 vs 8.9%, p = 0.77). None of the 7 stroke patients infected with COVID-19 died. During the COVID-19 pandemic, the number of stroke admissions fell, and stroke severity increased. There was no statistically significant change in the delivery of thrombolysis and mechanical thrombectomy and no increase in mortality.

Neurological manifestations of coronavirus disease 2019: exploring past to understand present.

Abstract: SARS-CoV-2 infection, resulting in Coronavirus disease 2019 (COVID-19), has significantly affected the entire world. It was labelled a pandemic by World Health Organization. Although it commonly produces respiratory symptoms, neurological features have been described. Neurological manifestations may vary from non-specific symptoms such as headache, dizziness, myalgia and/or fatigue, olfactory or taste dysfunction to specific syndromes including meningitis, stroke, acute transverse myelitis and Guillain-Barre syndrome. This review describes potential pathogenetic mechanisms and neurological manifestations of COVID-19 along with its management. Considering structural and pathogenetic similarity of SARS-CoV-2 with SARS-CoV and MERS viruses, we compared their neurological manifestations and mentioned few features expected in COVID-19 in future. Interestingly, many COVID-19 cases may present with pure neurological manifestations at onset with non-neurological features manifesting few days later and we propose the term "Neuro-COVID syndrome" for such cases. Awareness of neurological manifestations may facilitate its management and improve outcome in such patients.

Hereditary spastic paraplegia

Abstract: Hereditary spastic paraplegias (HSPs) are a group of neurodegenerative disorders which involve the corticospinal tracts and present with distinct spasticity and weakness of the lower extremities. The estimated prevalence of HSP is around 1.8/100,000 cases for both autosomal dominant and autosomal recessive types. Classification of HSP is based on inheritance pattern, clinical phenotype, and molecular pathophysiological mechanisms. The most common neuropathological sign is the axonal degeneration involving the lateral corticospinal tracts in both the cervical and thoracic spinal cord. The target of this review article is to provide a comprehensive overview of the HSP classification, neuropathology, and differential diagnosis.

Latent class cluster analysis identified hidden headache phenotypes in COVID-19: impact of pulmonary infiltration and IL-6.

Abstract: Clinical studies on COVID-19 headache are limited. This prospective study aimed to define headache characteristics, associated clinical and laboratory factors, and treatment response in COVID-19. Cross-sectional study enrolled 287 patients diagnosed with COVID-19 and hospitalized on a regular ward during the pandemic. All patients were examined face to face and followed by a neurologist during their stay in the hospital. The characteristics, concomitant symptoms, treatment responses, and laboratory findings of COVID-19-associated headaches were recorded. Eighty-three COVID-19 patients reported headache (28.9%), in which 85.5% had no prior headaches. Mean age was 48.40 ± 15.90 and 58% was men. Compared to COVID-19 patients without headache (n = 204), patients with headache showed significantly higher frequency of pulmonary involvement (76%) and increased D-dimer levels. Fifty-nine percent of headaches responded iv paracetamol 1000 mg, and 85% of the paracetamol unresponsive headaches were relieved by greater occipital nerve (GON) blocks. Latent class cluster analysis identified 2 distinct class of bilateral, frontal, throbbing headaches: severe (VAS > 84), longer (> 14 h), frequent (> 7 headache days), paracetamol unresponsive-GON responsive headaches (85%), with pulmonary involvement (100%), and higher IL-6 levels (> 90 pg/mL) were classified in cluster 1. Cluster 2 included moderately affected patients (VAS > 54, > 6 h, > 4 days, 60% pulmonary involvement, > 20 pg/mL IL-6) and paracetamol responsive headaches (96%). VAS scores showed positive linear correlation with IL-6 levels (p 70 severity, > 9 h duration, > 5 headache days, and IL-6 > 43 pg/mL levels can be diagnostic for COVID-19 headache. GON blocks can effectively abort headache when patients are unresponsive to paracetamol, and other NSAIDs are avoided during the SARS-CoV-2 infection.

Preliminary evidence of blunted humoral response to SARS-CoV-2 mRNA vaccine in multiple sclerosis patients treated with ocrelizumab.

Abstract: Several concerns regard the immunogenicity of SARS-CoV-2 vaccines in people with multiple sclerosis (pwMS), since the majority of them is treated with immunomodulating/immunosuppressive disease modifying therapies. Here we report the first data on the humoral response to mRNA SARS-CoV-2 vaccine in a case series of 4 pwMS treated with ocrelizumab (OCR) as compared to a group of healthy subjects (HS). We collected serum samples at 0, 14, 21 days after the first dose and 7 days after the second dose of BNT162b2-mRNA-Covid-19 vaccine from 55 health-care workers and 4 relapsing pwMS on OCR, with no history of Covid-19 infection. Sera were tested using the LIAISON®SARS-CoV-2 TrimericS-IgG assay (DiaSorin-S.p.A.) for the detection of IgG antibodies to SARS-CoV-2 spike protein. The anti-spike IgGtiters were expressed in Binding Antibody Units (BAU), an international standard unit. At baseline all subjects were negative for anti-spike IgG. Seven days after the second dose of vaccine all HS mounted a significant humoral response (geometric mean 2010.4 BAU/mL C.I. 95% 1512.7-2672) while the 4 pwMS showed a lower response (range <4.81-175 BAU/mL). Humoral response to BNT162b2-mRNA-vaccine in pwMS treated with OCR was clearly blunted. Further data are urgently needed to confirm and expand these preliminary results and to develop strategies to optimize the response to SARSCoV-2 vaccines in pwMS on OCR.

Diagnosis and treatment of Chiari malformation and syringomyelia in adults: international consensus document

Abstract: Syringomyelia and Chiari malformation are classified as rare diseases on Orphanet, but international guidelines on diagnostic criteria and case definition are missing. Aim of the study: to reach a consensus among international experts on controversial issues in diagnosis and treatment of Chiari 1 malformation and syringomyelia in adults. A multidisciplinary panel of the Chiari and Syringomyelia Consortium (4 neurosurgeons, 2 neurologists, 1 neuroradiologist, 1 pediatric neurologist) appointed an international Jury of experts to elaborate a consensus document. After an evidence-based review and further discussions, 63 draft statements grouped in 4 domains (definition and classification/planning/surgery/isolated syringomyelia) were formulated. A Jury of 32 experts in the field of diagnosis and treatment of Chiari and syringomyelia and patient representatives were invited to take part in a three-round Delphi process. The Jury received a structured questionnaire containing the 63 statements, each to be voted on a 4-point Likert-type scale and commented. Statements with agreement <75% were revised and entered round 2. Round 3 was face-to-face, during the Chiari Consensus Conference (Milan, November 2019). Thirty-one out of 32 Jury members (6 neurologists, 4 neuroradiologists, 19 neurosurgeons, and 2 patient association representatives) participated in the consensus. After round 2, a consensus was reached on 57/63 statements (90.5%). The six difficult statements were revised and voted in round 3, and the whole set of statements was further discussed and approved. The consensus document consists of 63 statements which benefited from expert discussion and fine-tuning, serving clinicians and researchers following adults with Chiari and syringomyelia.

Clinical and neurophysiological characterization of muscular weakness in severe COVID-19.

Abstract: To report clinical and electroneuromyographic (ENMG) characteristics of patients affected by severe COVID-19 infection, evaluated for muscular weakness. ENMGs performed for evaluation of diffuse weakness in patients who could not be discharged from semi-intensive care COVID unit because of difficulties in ventilation weaning were reviewed. Patients with severe COVID-19 infection who had undergone endotracheal intubation and able to co-operate were considered. ENMG protocol was focused on neurophysiological items that excluded or confirmed critical illness polyneuropathy (CIP), myopathy (CIM), or polyneuromyopathy (CIPM). Standardized clinical evaluation was performed using Medical Research Council (MRC) sum score. Eight patients were included in the study. All presented known risk factors for intensive care unit-acquired weakness (ICU-AW), and none of them had history of underlying neuromuscular disorders. ENMG findings were normal in two patients, while only two patients had an altered MRC sum score (< 48). Neuromuscular involvement was diagnosed in 6/8 patients (75%): 2 had CIP, 1 had possible CIM, 1 had CIPM, while 1 patient, with clinically evident weakness but equivocal ENMG findings, was classified as ICU-AW. Finally, 1 patient was diagnosed with acute demyelinating neuropathy. Patients with neuromuscular involvement were those with longer intubation duration and higher levels of IL-6 at admission. Neuromuscular complications are frequent in severe COVID-19 and cannot be excluded by MRC sum scores above 48. Standardized ENMG is helpful in guiding diagnosis when clinical evaluation is not reliable or possible. Elevated IL-6 at admission may be a predictor biomarker of ICU-AW in COVID-19.

Effectiveness of ketogenic diet in treatment of patients with refractory chronic migraine.

Abstract: Ketogenic diet (KD) is based on restriction of carbohydrate intake Metabolism is forced to obtain energy starting from β-oxidation of fatty acids which, turned into ketone bodies, can also be used by central nervous system (CNS) KD use in treatment of chronic migraine has recently been considered We set out to verify modification of symptoms in patients with refractory chronic migraine in response to KD Fifty patients were enrolled of which 38 completed the procedures the study and 23 were considered in the statistics All of the patients considered in our study were affected by medication overuse headache (MOH) They were on a KD for 3 months The following parameters have been checked at t = 0 and every 30 days for 6 months: migraine episode length (n hours/day), frequency (n days/month), level of pain of every episode measured on a scale from 1 to 3 (1 = mild; 2 = moderate; 3 = severe), and n analgesic drugs taken/month Days with symptoms decreased from 30 (median value) to 75 with p < 00001 The duration of the migraine episodes decreased from 24 h (median value) to 55 h with p < 00016 The patients’ pain level, initially at maximum value for 83% of the participants, improved for 55% of them (p < 00024) The number of drugs taken in a month decreased from 30 doses (median value) to 6 doses It can be stated that a 3-month KD resulted in a reduction of painful symptoms of drug refractory chronic migraine This result may suggest an improvement in quality of life of the patients, even without a tabulated data collection

Characteristics, onset, and evolution of neurological symptoms in patients with COVID-19.

Abstract: A wide range of neurological manifestations has been described in COVID-19. In this nationwide retrospective observational study, patients in Tunisia diagnosed with COVID-19 between the 2nd of March and the 16th of May 2020 were contacted by telephone. We collected demographic and clinical data and specified characteristics and evolution of main neurological symptoms. Of 1034 confirmed COVID-19 patients, 646 were included (mean age 42.17 years old) and 466 (72.1%) had neurological symptoms. Neurological symptoms were isolated 22.7% (n = 106). Headache was the most frequent neurological symptom (n = 279, 41.1%): mainly frontotemporal (n = 143, 51.1%) and mild or moderate (n = 165, 59.1%). When associated with fever (n = 143, 51.3%), headache was more likely to be severe and present at onset. Recovery was reported in 83.2%. Smell and taste impairment were found in 37.9% (n = 245) and 36.8% (n = 238) respectively. Among them, 65.3% (156/239) were anosmic and 63.2% (146/231) were ageusic. A complete improvement was found in 72.1% (174/240) of smell impairment and in 76.8% (179/233) of taste impairment. Myalgia (n = 241, 37.3%) and sleep disturbances (n = 241, 37.3%) were also frequent. Imported cases had more neurological symptoms (p = 0.001). In 14.5%, neurological symptoms preceded the respiratory signs (RS). RS were associated with more frequent (p = 0.006) and numerous (p < 0.001) neurological symptoms. Neurological symptoms in COVID-19 are frequent, can be isolated and present at onset. A total recovery is the most recorded outcome. RS are predictive of neurological symptoms. Studies in to virus and host genetics should be considered to understand the different phenotypes.

Life with chronic pain during COVID-19 lockdown: the case of patients with small fibre neuropathy and chronic migraine.

Abstract: We aimed at investigating the impact of COVID-19-related distress on patients with chronic pain, highlighting the effects of changes in individual habits and public health care reconfiguration on physical and psychological health. During the pandemic, 80 participants (25 patients with small fibre neuropathy (SFN), 42 patients with chronic migraine (CM) and 13 patients’ healthy family members (HFM)) were asked to evaluate their COVID-19 complains, changes in habits and clinical management, behaviour, mood, loneliness, quality of life (QoL), physical and mental health and coping strategies. Data were analysed by Spearman rho correlations and Mann-Whitney U tests. Patients had lower QoL, lower physical health and higher catastrophizing attitude towards pain than HFM. During the pandemic, SFN patients referred greater decline in clinical symptoms, worries about contagion and discomfort for disease management changes than CM patients. In the SFN group, the higher levels of disability were associated with suffering from changes in neurologist-patient relationship. CM patients complained of agitation/anxiety that was related to feelings of loneliness, depressive mood and catastrophism. Despite similar complains of change in habits and worries about COVID-19 pandemic, SFN and CM patients had distinct reactions. In SFN patients, pandemic distress impacted on physical health with worsening of clinical conditions, especially suffering from changes in their care. In CM patients, pandemic distress affected behaviour, mainly with psychological frailty. This suggests the need to customize public health care for patients with distinct chronic pain conditions.

Subjective cognitive failures and their psychological correlates in a large Italian sample during quarantine/self-isolation for COVID-19.

Abstract: The quarantine/self-isolation measures implemented to retard the spread of the 2019 coronavirus disease (COVID-19) may negatively affect the mental health of the population. The present study aimed to explore the impact of the psychological symptoms on the occurrence of cognitive failures in a large sample of home-dwelling Italian individuals during quarantine/self-isolation for COVID-19. We employed an online questionnaire using a virtual platform of Google Moduli. The questionnaire included an assessment of cognitive failures evaluated by the Perceived Memory and Attentional Failures Questionnaire (PerMAFaQ) and of resilience, coping style, depression, anger, and anxiety. The online questionnaire was completed by 4175 participants revealing that about 30% of participants complained of cognitive failures at least sometimes during quarantine/self-isolation, whereas some respondents reported very frequent cognitive failures. Moreover, resilience was found to mediate the relationships between depressive and anger symptoms and cognitive failures. Although no difference was found on PerMAFaQ among smart-workers, non-smart-workers, and those currently not at work, people not working at the moment complained of more frequent cognitive failures. These findings indicate the need to implement psychological support intervention, particularly for vulnerable groups, to reduce anxiety, depression, and anger, and of psychoeducational interventions to enhance resilience reducing possible long-term cognitive consequences of the quarantine.