Successful systemic lysis therapy of a floating carotid thrombus in an acute stroke patient with known immune thrombocytopenic purpura on ongoing eltrombopag therapy and acute COVID-19 infection: A case report (preprint)

Background: Patients with immune thrombocytopenic purpura (ITP) under eltrombopag therapy are vulnerable to thrombotic disbalance either by disease and by therapy-related hypercoagulability. Vascular events such as the development of a free-floating carotid thrombus are known rare complications of acute COVID-19 infections due to an endothelial inflammation and underlying hypercoagulable state. New focal neurological symptoms in patients at risk should be immediately followed by angiographic diagnostics and, if necessary, proceed with the appropriate treatment immediately. Case presentation: Here we report a case of a 38-old female with a medical history of ITP and presence of COVID-19 infection presenting an acute sensorimotor hemiparesis of the right side while oneltrombopag therapy. Initial CT angiography revealed a free-floating thrombus of the left carotid artery. At admission, platelet number was significantly increased at 896/nl. After systemic lysis therapy the thrombus was fully dissolved. Follow-up diffusion-weighted imaging revealed multilocular cortical infarction of the left ACM territory. The patient soon recovered and was released with residual mild sensorimotor deficits of the right arm. Eltrombopag was paused at admission, platelet number was quickly normalizing and the patient was discharged with a daily intake of acetylsalicylic acid, eltrombopag in reduced daily dose and weekly control of platelet number for 3 months. Conclusions: This unique case enhances the need for caution in patients at vascular risk who exhibit an acute COVID-19 infection, and discusses thrombocytic derailment under thrombopoietin receptor agonist therapy associated with an acute COVID-19 infection.

Real-World Data on the Incidence and Risk of Guillain-Barre Syndrome Following SARS-CoV-2 Vaccination: A Prospective Surveillance Study (preprint)

Increasing evidence suggests an association between SARS-CoV-2 vaccines and Guillain-Barré syndrome (GBS). Nevertheless, little is understood about the contributing risk factors and clinical characteristics of GBS post SARS-CoV-2 vaccination. In this prospective surveillance study of 38,828,692 SARS-CoV-2 vaccine doses administered from February 2021 to March 2022 in the Gyeonggi Province, South Korea, 55 cases of GBS were reported post vaccination. We estimated the incidence rate of GBS per million doses and the incidence rate ratio for the vaccine dose, mechanism, age, and sex. Additionally, we compared the clinical characteristics of GBS following mRNA-based and viral vector-based vaccinations. The overall incidence of GBS following SARS-CoV-2 vaccination was 1.42 per million doses. Viral vector-based vaccines were associated with a higher risk of GBS. Men were more likely to develop GBS than women. The third dose of vaccine was associated with a lower risk of developing GBS. Classic sensorimotor and pure motor subtypes were the predominant clinical subtypes, and demyelinating type was the predominant electrodiagnostic subtype. The initial dose of viral-vector based vaccine and later doses of mRNA-based vaccine were associated with GBS, respectively. GBS following SARS-CoV-2 vaccination may not be clinically distinct. However, physicians should pay close attention to the classic presentation of GBS in men receiving an initial dose of viral vector-based SARS-CoV-2 vaccines.

Intensive Care Unit- Acquired Weakness and Hospital Functional Mobility Outcomes Following Invasive Mechanical Ventilation in Patients with COVID-19: A Single-Centre Prospective Cohort Study.

Background: Acute physical function outcomes in ICU survivors of COVID-19 pneumonia has received little attention. Critically ill patients with COVID-19 infection who require invasive mechanical ventilation may undergo greater exposure to some risk factors for ICU-acquired weakness (ICUAW). Purpose: To determine incidence and factors associated with ICUAW at ICU discharge and gait dependence at hospital discharge in mechanically ventilated patients with COVID-19 pneumonia. Methods: Single-centre, prospective cohort study conducted at a tertiary hospital in Madrid, Spain. We evaluated ICUAW with the Medical Research Council Summary Score (MRC-SS). Gait dependence was assessed with the Functional Status Score for the ICU (FSS-ICU) walking subscale. Results: During the pandemic second wave, between 27 July and 15 December, 2020, 70 patients were enrolled. ICUAW incidence was 65.7% and 31.4% at ICU discharge and hospital discharge, respectively. Gait dependence at hospital discharge was observed in 66 (54.3%) patients, including 9 (37.5%) without weakness at ICU discharge. In univariate analysis, ICUAW was associated with the use of neuromuscular blockers (crude odds ratio [OR] 9.059; p = 0.01) and duration of mechanical ventilation (OR 1.201; p = 0.001), but not with the duration of neuromuscular blockade (OR 1.145, p = 0.052). There was no difference in corticosteroid use between patients with and without weakness. Associations with gait dependence were lower MRC-SS at ICU discharge (OR 0.943; p = 0.015), older age (OR 1.126; p = 0.001), greater Charlson Comorbidity Index (OR 1.606; p = 0.011), longer duration of mechanical ventilation (OR 1.128; p = 0.001) and longer duration of neuromuscular blockade (OR 1.150; p = 0.029). Conclusions: In critically ill COVID-19 patients, the incidence of ICUAW and acute gait dependence were high. Our study identifies factors influencing both outcomes. Future studies should investigate optimal COVID-19 ARDS management and impact of dyspnea on acute functional outcomes of COVID-19 ICU survivors.

Individuals with a COVID-19 history exhibit asymmetric gait patterns despite full recovery.

COVID-19 is a multisystem infectious disease affecting the body systems. Its neurologic complications include -but are not limited to headache, loss of smell, encephalitis, and cerebrovascular accidents. Even though gait analysis is an objective measure of the neuro-motor system and may provide significant information about the pathophysiology of specific diseases, no studies have investigated the gait characteristics in adults after full recovery from COVID-19. This was a cross-sectional, controlled study that included 12 individuals (mean age, 23.0 ± 4.1 years) with mild-to-moderate COVID-19 history (COVD) and 20 sedentary controls (CONT; mean age, 24.0 ± 3.6 years). Gait was evaluated using inertial sensors on a motorized treadmill. Spatial-temporal gait parameters and gait symmetry were calculated by using at least 512 consecutive steps for each participant. The effect-size analyses were utilized to interpret the impact of the results. Spatial-temporal gait characteristics were comparable between the two groups. The COVD group showed more asymmetrical gait patterns than the CONT group in the double support duration symmetry (p = 0.042), single support duration symmetry (p = 0.006), loading response duration symmetry (p = 0.042), and pre-swing duration symmetry (p = 0.018). The effect size analyses of the differences showed large effects (d = 0.68-0.831). Individuals with a history of mild-to-moderate COVID-19 showed more asymmetrical gait patterns than individuals without a disease history. Regardless of its severity, the multifaceted long-term effects of COVID-19 need to be examined and the scope of clinical follow-up should be detailed.

Stay mindfully active during the coronavirus pandemic: a feasibility study of mHealth-delivered mindfulness yoga program for people with Parkinson's disease.

IMPORTANCE: Patients with long-term neurological conditions, such as Parkinson's disease (PD), are particularly vulnerable to the public health measures taken to combat the COVID-19 pandemic. The inaccessibility of center-based rehabilitation further aggravated their motor dysfunctions as well as mental distress, leading to exacerbation of motor and non-motor symptoms, high healthcare utilization and worsened health-related quality of life (HRQOL). OBJECTIVE: This study aimed to evaluate the feasibility, safety, and preliminary effects of the mHealth-delivered home-based mindfulness yoga program on functional balance, motor symptoms, mental health and HRQOL in patients with PD. DESIGN, SETTING AND PARTICIPANTS: This prospective, single-arm, non-randomized feasibility study adopted a sequential explanatory mixed-method design. Adults (aged ≥ 18) with a clinical diagnosis of idiopathic Parkinson's disease (Hoehn and Yahr stage I to III) who were able to stand unaided and walk with or without an assistive device were enrolled via convenience sampling. INTERVENTION: Home-based mindfulness yoga training were delivered via video-conferencing software (Zoom) in eight bi-weekly 90-min sessions. MAIN OUTCOMES AND MEASURES: This current study measured functional balance, motor symptoms, perceived balance confidence, perceived freezing of gait symptoms, anxiety and depression, mindfulness and HRQOL using a tele-assessment approach at baseline and 1-week post-intervention. All participants were invited to attend qualitative individual interviews to explore their experience of using online mindfulness yoga program as a lifestyle intervention for PD rehabilitation. RESULTS: Among the ten patients, 80% completed the program with an adherence rate of 98.4%. All participants were able to learn and practice mindfulness yoga following the eight bi-weekly online mindfulness yoga training sessions, without any significant adverse events. Tele-assessment of outcomes were feasible and uneventful. Qualitative feedback revealed participants had a high preference of using the tele-rehabilitation approach to stay mindful and being active, both physically and socially, while confronting the changes brought by COVID-19 pandemic. CONCLUSIONS AND RELEVANCE: The mHealth-delivered home-based mindfulness yoga intervention was feasible, safe, and well-accepted among people with PD to relieve the burden brought by COVID-19 pandemic. Future studies should adopt a design with enhanced rigor, a comparison group, and enlarged sample size to evaluate the efficacy of the program in patients with long-term neurological conditions and/or physical impairments. We recommend a longer intervention duration of at least 8 weeks to enhance the psychophysiological effects.

Impact of social and mobility restrictions in Parkinson's disease during COVID-19 lockdown.

BACKGROUND: The consequences of strict COVID-19 mobility restrictions on motor/non-motor features in Parkinson's disease (PD) have not been systematically studied but worse mobility and quality of life have been reported. To elucidate this question, 12 mild to moderate PD patients were assessed in March 2020 before and after two months of isolation as part of a clinical study that had to be interrupted due to the pandemic and the implementation of COVID19 mobility restrictions. METHODS: Twelve patients were systematically evaluated before and after the lockdown period as part of a larger cohort that previously underwent thermal water rehabilitation. Clinical outcomes were the Body Mass index, the Mini-Balance Evaluation Systems Test, the MDS-Unified Parkinson's Disease Rating Scale part III, the 6 Minute Walking Test and the New Freezing of Gait Questionnaire. Global cognition was evaluated with the Montreal Cognitive Assessment scale. The impact of COVID-19 restrictions on quality of life and functional independence was evaluated with The Parkinson's disease Quality of life (PDQ-39), the Activities of Daily Living (ADL) and Instrumental Activities of Daily Living questionnaires (IADL) and the Parkinson's disease cognitive functional rating scales (PD-CFRS). RESULTS: After two months of isolation the Mini-BESTest score worsened (p=0.005), and four patients reported one or more falls during the lockdown. BMI increased (p=0.031) while the remaining clinical variables including quality of life did not change. CONCLUSION: We observed moderate worsening at Mini-BESTest, greater risk of falls and increased body weight as consequence of prolonged immobility. We believe negative effects were partially softened since patients were in contact with our multidisciplinary team during the lockdown and had previously received training to respond to the needs of this emergency isolation. These findings highligh the importnace of patient-centered interventions in PD management.

Normal Pressure Hydrocephalus Associated with COVID-19 Infection: A Case Report (preprint)

COVID-19 is a pandemic disease responsible for a large number of deaths worldwide. Many neurological manifestations have been described. We report a case of normal pressure hydrocephalus (NPH) two months after acute COVID19 infection, in a patient without other risk factors. A 45-year-old male patient presented an 8-month history of progressive gait disorder and cognitive impairment after being hospitalized for SARS-CoV-2 infection. Magnetic resonance imaging (MRI) was compatible with NPH. A spinal tap test was positive and there was progressive improvement after shunting, with complete resolution of symptoms. Other infections such Syphilis, cryptococcosis and Lyme disease have been associated with NPH. Possible mechanisms for NPH after COVID include disruption of choroid plexus cells by direct viral invasion or as a result of neuroinflammation and cytokine release and hypercoagulability leading to venous congestion and abnormalities of CSF flow. Given the significance of NPH as a cause of reversible dementia, it is important to consider the possibility of a causal association with COVID19 and understand the mechanisms behind this association.

INFLUENCE OF NOVEL CORONAVIRUS DISEASE (COVID-19) ON PARKINSONS DISEASE: SYSTEMATIC REVIEW (preprint)

Background: The novel Coronavirus (COVID 19) infection has affected the population with various medical issues including the underlying neurological comorbidities such as Parkinson disease. COVID 19 is found to bind with the host angiotensin-converting enzyme 2 (ACE2) receptors for viral entry. ACE2 receptors are normally expressed in various body surfaces as well as in the neurons and glial cells where they act as an entry port to SARS-CoV-2 infection to invade the central nervous system (CNS). ACE2 are also highly expressed in dopamine neurons which might worsen the outcome in terms of motor symptoms in PD with the treatment course. It may lead to an indirect response via immune-mediated cytokine storms and propagate through CNS leading to damage. Parkinsons disease has also been noticed due to certain post viral infections apart from COVID-19 such as, HSV, Influenza virus A, Measles virus, Cytomegalovirus and Mumps (Olsen et al, 2018). We aim to provide a thorough review on neurological outcomes and impact of COVID-19 in Parkinson disease. Methods: A systematic review was conducted to analyze the impact of COVID 19 in patients with Parkinson disease (> 21 yo). Systematic literature search was done using PubMed, Science Direct, Google Scholar and Cochrane databases. PRISMA guidelines were followed summarized in Fig. 3 for study acquisition. Results: Of the Parkinsons patients that were tested positive for SARS-CoV 2, worsening of motor symptoms were reported along with other COVID 19 symptoms (Fig. 4 and 5). These symptoms include bradykinesia, tremors, gait disturbances, delirium and dementia and severe spasms of arms and legs. Encephalopathy was also one of the main symptoms presented in two of the studies. Increased mortality rates were identified for those who were hospitalized due to COVID-19 and PD when compared to other patients. Conclusion: Parkinsons disease may experience substantial worsening of motor and non motor symptoms during COVID 19. Due to the novelty of the virus, studies were reported from recent years and further extensive studies are needed to explore more about the disease severity and neurological outcomes when compared to other non-PD patients. Authors identify this as a limitation for this paper. Additional studies are needed to understand the role of ACE2 in increasing vulnerability to viruses and role of ACE inhibitors as treatment modality.

Navigating Through a COVID-19 World: Avoiding Obstacles.

Individuals with balance and gait problems encounter additional challenges navigating this post-coronavirus disease-2019 (COVID-19) world. All but the best fitting facemasks partially obscure the lower visual field. Facemask use by individuals with balance and gait problems has the potential to further compromise walking safety. More broadly, as the world reopens for business, balance and gait testing in clinics and research laboratories will also be impacted by facemask use. Here, we highlight some of the challenges faced by patients, clinicians, and researchers as they return to "normal" after COVID-19.Video Abstract is available for insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A328).

Post nCoV-2 limping Child: Report of two cases and a rapid Review (preprint)

Background: Identification of the etiology of acute limping in children is challenging. Both benign and life- threatening disorders can present with limp. However, among atraumatic conditions, benign conditions including toxic synovitis and post infectious arthritis are the most common causes of this dilemma. Case Presentation: During the recent COVID-19 pandemic in Kerman, South East of Iran; two pediatric patients referred to the Rheumatology clinic with new onset gait disturbance. One 8 years old boy and the other 6 years old girl who presented with hip joint pain and limping. Both of them had joint effusion jackknife of mild respiratory symptoms and fever. Altogether, precise history taking and accurate physical examination, alongside radiological investigations and positive laboratory results for coronavirus infection emphasized the diagnosis of post Coronavirus arthritis.  They treated with rest and Non-Steroidal Anti-Inflammatory Drugs (NSAID) successfully, and fallowed at least for one month later.Conclusions: Here, we described the first report of post n-CoV-2 arthritis in the world in two Iranian pediatric patients, who presented with limp. Contrary to preliminary phantasms, this may indicate that the Corona virus has some rheumatogenic specifications.