Polymyxin-induced neuromuscular weakness: a case report.

Polymyxin-induced neuromuscular blockade is a rare but potentially fatal condition, with majority of cases that were reported between 1962 and 1973. We describe a patient who developed hypercapnic respiratory failure after initiation of polymyxin for multi-drug resistant Escherichia Coli bacteremia, due to polymyxin-induced neuromuscular dysfunction. After cessation of polymyxin, he regained full strength, had complete resolution of ptosis, and was successfully extubated. In light of the renewed use of polymyxin in this era of antimicrobial-resistance, this case aims to raise awareness about this rare but life-threatening condition, which is easily reversible with early recognition and prompt discontinuation of the drug.

Enhanced external counter pulsation therapy in patients with symptomatic and severe intracranial steno-occlusive disease: a randomized clinical trial protocol.

Intracranial stenosis is prevalent among Asians and constitutes a common cause of cerebral ischemia. While the best medical therapy carries stroke recurrence rates in excess of 10% per year, trials with intracranial stenting have been associated with unacceptable peri-procedural ischemic events. Cerebral ischemic events are strongly related to the severity of intracranial stenosis, which is high in patients with severe intracranial stenosis with poor vasodilatory reserve. Enhanced External Counter Pulsation (EECP) therapy is known to improve myocardial perfusion by facilitating the development of collateral blood vessels in the heart. In this randomized clinical trial, we evaluate whether EECP therapy may be useful in patients with severe stenosis of intracranial internal carotid (ICA) or middle cerebral artery (MCA). The review of literature, methods of evaluation, status of currently used therapeutic approaches, and trial protocol have been presented. Clinical trial registration: ClinicalTrials.gov, Identifier: NCT03921827.

Bridging the Gap: Tailoring an Approach to Treatment in Febrile Infection-Related Epilepsy Syndrome.

Cytokine profiling before immunotherapy is increasingly prevalent in febrile infection-related epilepsy syndrome (FIRES). In this case, an 18-year-old man presented with first-onset seizure after a nonspecific febrile illness. He developed super-refractory status epilepticus requiring multiple antiseizure medications and general anesthetic infusions. He was treated with pulsed methylprednisolone and plasma exchange and started on ketogenic diet. Contrast-enhanced MRI brain revealed postictal changes. EEG findings showed multifocal ictal runs and generalized periodic epileptiform discharges. CSF analysis, autoantibody testing, and malignancy screening were unremarkable. Genetic testing revealed variants of uncertain significance in the CNKSR2 and OPN1LW genes. Initial serum and CSF cytokine analyses performed on days 6 and 21 revealed that interleukin (IL)-6, IL-1RA, monocyte chemoattractant protein-1, macrophage inflammatory protein 1ß, and interferon γ were elevated predominantly in the CNS, a profile consistent with cytokine release syndrome. Tofacitinib was initially trialed on day 30 of admission. There was no clinical improvement, and IL-6 continued to rise. Tocilizumab was given on day 51 with significant clinical and electrographic response. Anakinra was subsequently trialed from days 99 to 103 because clinical ictal activity re-emerged on weaning anesthetics but stopped because of poor response. Serial cytokine profiles showed improvement after 7 doses of tocilizumab. There was corresponding improved seizure control. This case illustrates how personalized immunomonitoring may be helpful in cases of FIRES, where proinflammatory cytokines are postulated to act in epileptogenesis. There is an emerging role for cytokine profiling and close collaboration with immunologists for the treatment of FIRES. The use of tocilizumab may be considered in patients with FIRES with upregulated IL-6.

Low incidence of neurological recurrent side-effects following COVID-19 reimmunization.

BACKGROUND: Individuals who suffered a neurological adverse event after the Coronavirus disease (COVID-19) vaccine could hesitate and defer reimmunization. AIM: We examine the risk of recurrence following reimmunization among patients who developed a neurological event after the first dose of the COVID-19 mRNA vaccine. DESIGN: Observational study. METHODS: Individuals who developed an adjudicated neurological adverse event (based on Brighton Collaboration criteria) within 6 weeks of the first dose of the COVID-19 vaccine requiring hospitalization were enrolled into a multicenter national registry in Singapore. Neurological recurrence, defined by the development of another neurological event within 6 weeks of the second vaccine dose, was reviewed. Clinical characteristics were compared between patients who chose to proceed or withhold further vaccination, and between those who received timely (3-6 weeks) or delayed (>6 weeks) reimmunization. RESULTS: From 235 patients (median age, 67 years; 63% men) who developed an adjudicated neurological event after their first dose of mRNA vaccine between 30 December 2020 and 20 April 2021, 181 (77%) chose to undergo reimmunization. Those who decided against reimmunization were older (median age, 74 vs. 66 years) and had greater physical disability following their primary neurological event (46% vs. 20%, P < 0.001). Patients who suffered greater physical disability were three times more likely to delay their reimmunization (odds ratio 3.36, 95% confidence interval: 1.76-6.40). Neurological recurrence was observed in only four individuals (three with seizures and one with myasthenia gravis exacerbation). CONCLUSIONS: A prior neurological event should not necessarily preclude reimmunization and the decision to proceed with reimmunization should consider the overwhelming benefits conferred by vaccination toward ending this pandemic.

Aseptic meningitis after BNT-162b2 COVID-19 vaccination.

The COVID-19 pandemic has had an unprecedented impact on healthcare systems globally, giving rise to significant morbidity and mortality. Vaccination has been widely regarded as the most important strategy to contain the pandemic. Whilst local side-effects of the BNT-162b2 (Pfizer-BioNTech) vaccine are well known, concern has emerged due to sporadic reports of immune-mediated adverse effects (Cines and Bussel, 2021; Rela et al., 2021). As of August 19, 2021, 4.54 million individuals had received COVID-19 vaccines in Singapore (Oxford Martin School UoO, 2021). We report a case series of two patients who developed aseptic meningitis after vaccination.

Hospital-based observational study of neurological disorders in patients recently vaccinated with COVID-19 mRNA vaccines.

PURPOSE: We describe the spectrum of acute neurological disorders among hospitalized patients who recently had COVID-19 mRNA vaccination. METHOD: We performed a prospective study at 7 acute hospitals in Singapore. Hospitalized patients who were referred for neurological complaints and had COVID-19 mRNA vaccines, BNT162b2 and mRNA-1273, in the last 6 weeks were classified into central nervous system (CNS) syndromes, cerebrovascular disorders, peripheral nervous system (PNS) disorders, autonomic nervous system (ANS) disorders and immunization stress-related responses (ISRR). RESULTS: From 30 December 2020 to 20 April 2021, 1,398,074 persons (median age 59 years, 54.5% males) received COVID-19 mRNA vaccine (86.7% BNT162b2, 13.3% mRNA-1273); 915,344(65.5%) completed 2 doses. Four hundred and fifty-seven(0.03%) patients were referred for neurological complaints [median age 67(20-97) years, 281(61.5%) males; 95.8% received BNT162b2 and 4.2% mRNA-1273], classified into 73(16.0%) CNS syndromes, 286(62.6%) cerebrovascular disorders, 59(12.9%) PNS disorders, 0 ANS disorders and 39(8.5%) ISRRs. Eleven of 27 patients with cranial mononeuropathy had Bell's palsy. Of 33 patients with seizures, only 4 were unprovoked and occurred within 2 weeks of vaccination. All strokes occurred among individuals with pre-existing cardiovascular risk factors. We recorded 2 cases of cerebral venous thrombosis; none were vaccine-induced thrombotic thrombocytopenia. Five had mild flares of immune-mediated diseases. CONCLUSION: Our observational study does not establish causality of the described disorders to vaccines. Though limited by the lack of baseline incidence data of several conditions, we observed no obvious signal of serious neurological morbidity associated with mRNA vaccination. The benefits of COVID-19 vaccination outweigh concerns over neurological adverse events.

Ocular surface disease in psoriatic patients in a developing country.

PURPOSE: To evaluate ocular surface changes among patients with psoriasis in Malaysia, a developing country in Southeast Asia. METHODS: An interdisciplinary case-control study (60 psoriasis patients and 40 control subjects) to look at the differences in ocular surface manifestations between patients with psoriasis and a group of age-, gender- and ethnicity-matched healthy controls. RESULTS: One hundred and twenty eyes of 60 patients with psoriasis and 80 eyes of 40 healthy controls without psoriasis were included in the study. Mild-to-moderate psoriasis was found in 42 patients (70%), while 18 patients (30%) had severe psoriasis. Psoriatic arthritis was found in 19 patients (32%). Of the 60 psoriatic patients, the prevalence of ocular involvement was 65% (39/60), in which 32% (19/60) had dry eyes, 27% (16/60) had lid margin abnormalities, 33% (20/60) had cataract, and one had history of anterior uveitis. Compared to controls, ocular surface of psoriatic patients showed more eyelid margin abnormalities, higher meibomian gland loss and lower tear film break-up time. The estimated odds ratio for dry eyes in the psoriasis group was 2.2 (95% CI: 0.8-6.9). CONCLUSION: Ocular surface disorders encompassing eyelid margin abnormalities, meibomian gland loss and tear dysfunction occur at an earlier and higher rate among psoriatic patients.

Neurology of COVID-19 in Singapore.

PURPOSE: To describe the spectrum of COVID-19 neurology in Singapore. METHOD: We prospectively studied all microbiologically-confirmed COVID-19 patients in Singapore, who were referred for any neurological complaint within three months of COVID-19 onset. Neurological diagnoses and relationship to COVID-19 was made by consensus guided by contemporaneous literature, refined using recent case definitions. RESULTS: 47,572 patients (median age 34 years, 98% males) were diagnosed with COVID-19 in Singapore between 19 March to 19 July 2020. We identified 90 patients (median age 38, 98.9% males) with neurological disorders; 39 with varying certainty of relationship to COVID-19 categorised as: i) Central nervous system syndromes-4 acute disseminated encephalomyelitis (ADEM) and encephalitis, ii) Cerebrovascular disorders-19 acute ischaemic stroke and transient ischaemic attack (AIS/TIA), 4 cerebral venous thrombosis (CVT), 2 intracerebral haemorrhage, iii) Peripheral nervous system-7 mono/polyneuropathies, and a novel group, iv) Autonomic nervous system-4 limited dysautonomic syndromes. Fifty-one other patients had pre/co-existent neurological conditions unrelated to COVID-19. Encephalitis/ADEM is delayed, occurring in critical COVID-19, while CVT and dysautonomia occurred relatively early, and largely in mild infections. AIS/TIA was variable in onset, occurring in patients with differing COVID-19 severity; remarkably 63.2% were asymptomatic. CVT was more frequent than expected and occurred in mild/asymptomatic patients. There were no neurological complications in all 81 paediatric COVID-19 cases. CONCLUSION: COVID-19 neurology has a wide spectrum of dysimmune-thrombotic disorders. We encountered relatively few neurological complications, probably because our outbreak involved largely young men with mild/asymptomatic COVID-19. It is also widely perceived that the pandemic did not unduly affect the Singapore healthcare system.

Powered Air Purifying Respirator (PAPR) restores the N95 face mask induced cerebral hemodynamic alterations among Healthcare Workers during COVID-19 Outbreak.

BACKGROUND AND AIM: COVID-19 pandemic has resulted in an unprecedented increased usage of Personal protective equipment (PPE) by healthcare-workers. PPE usage causes headache in majority of users. We evaluated changes in cerebral hemodynamics among healthcare-workers using PPE. METHODS: Frontline healthcare-workers donning PPE at our tertiary center were included. Demographics, co-morbidities and blood-pressure were recorded. Transcranial Doppler (TCD) monitoring of middle cerebral artery was performed with 2-MHz probe. Mean flow velocity (MFV) and pulsatility index (PI) were recorded at baseline, after donning N95 respirator-mask, and after donning powered air-purifying respirator (PAPR), when indicated. End-tidal carbon-dioxide (ET-CO2) pressure was recorded for participants donning PAPR in addition to the N95 respirator-mask. RESULTS: A total of 154 healthcare-workers (mean age 29 ± 12 years, 67% women) were included. Migraine was the commonest co-morbidity in 38 (25%) individuals while 123 (80%) developed de-novo headache due to N95 mask. Donning of N95 respirator-mask resulted in significant increase in MFV (4.4 ± 10.4 cm/s, p < 0.001) and decrease in PI (0.13 ± 0.12; p < 0.001) while ET-CO2 increased by 3.1 ± 1.2 mmHg (p < 0.001). TCD monitoring in 24 (16%) participants donning PAPR and N95 respirator mask together showed normalization of PI, accompanied by normalization of ET-CO2 values within 5-min. Combined use of N95 respirator-mask and PAPR was more comfortable as compared to N95 respirator-mask alone. CONCLUSION: Use of N95 respirator-mask results in significant alterations in cerebral hemodynamics. However, these effects are mitigated by the use of additional PAPR. We recommend the use of PAPR together with the N95 mask for healthcare-workers doing longer duties in the hospital wards.

Impact of the COVID-19 pandemic on hyperacute stroke treatment: experience from a comprehensive stroke centre in Singapore.

The Coronavirus disease 2019 (COVID-19) pandemic is rapidly evolving and affecting healthcare systems across the world. Singapore has escalated its alert level to Disease Outbreak Response System Condition (DORSCON) Orange, signifying severe disease with community spread. We aimed to study the overall volume of AIS cases and the delivery of hyperacute stroke services during DORSCON Orange. This was a single-centre, observational cohort study performed at a comprehensive stroke centre responsible for AIS cases in the western region of Singapore, as well as providing care for COVID-19 patients. All AIS patients reviewed as an acute stroke activation in the Emergency Department (ED) from November 2019 to April 2020 were included. System processes timings, treatment and clinical outcome variables were collected. We studied 350 AIS activation patients admitted through the ED, 206 (58.9%) pre- and 144 during DORSCON Orange. Across the study period, number of stroke activations showed significant decline (p = 0.004, 95% CI 6.513 to - 2.287), as the number of COVID-19 cases increased exponentially, whilst proportion of activations receiving acute recanalization therapy remained stable (p = 0.519, 95% CI - 1.605 to 2.702). Amongst AIS patients that received acute recanalization therapy, early neurological outcomes in terms of change in median NIHSS at 24 h (-4 versus -4, p = 0.685) were largely similar between the pre- and during DORSCON orange periods. The number of stroke activations decreased while the proportion receiving acute recanalization therapy remained stable in the current COVID-19 pandemic in Singapore.

The face mask: How a real protection becomes a psychological symbol during Covid-19?

'The Mask' has become a byword and a precious possession universally. Except for its use by the medical fraternity, answers to the common questions-whether it provides enough protection, which type is optimal for the general public and who really needs to don it, remain poorly understood. For a frontline healthcare worker, wearing mask is a necessity as an important person protection equipment, it is perhaps the most-powerful psychological symbol for the general public. Surprisingly, it even undermines all other recommended practices of infection control and breaking the transmission chain of Covid-19, like hand washing, personal hygiene and social distancing. 'The mask' has evolved with time and yet there is a need to further improve the design for safety, tolerability and comfort. In this review we present the journey of face mask, originating from the first masks aimed at stopping the bad smell to its industrial use to its all-important place in the medical field. Various types of face masks, their filtration efficiency, reusability and current recommendations for their use are presented.

A multinational, multicentre study on the psychological outcomes and associated physical symptoms amongst healthcare workers during COVID-19 outbreak.

OBJECTIVE: Since the declaration of the coronavirus 2019 (COVID-19) outbreak as pandemic, there are reports on the increased prevalence of physical symptoms observed in the general population. We investigated the association between psychological outcomes and physical symptoms among healthcare workers. METHODS: Healthcare workers from 5 major hospitals, involved in the care for COVID-19 patients, in Singapore and India were invited to participate in a study by performing a self-administered questionnaire within the period of February 19 to April 17, 2020. Healthcare workers included doctors, nurses, allied healthcare workers, administrators, clerical staff and maintenance workers. This questionnaire collected information on demographics, medical history, symptom prevalence in the past month, Depression Anxiety Stress Scales (DASS-21) and the Impact of Events Scale-Revised (IES-R) instrument. The prevalence of physical symptoms displayed by healthcare workers and the associations between physical symptoms and psychological outcomes of depression, anxiety, stress, and post-traumatic stress disorder (PTSD) were evaluated. RESULTS: Out of the 906 healthcare workers who participated in the survey, 48 (5.3%) screened positive for moderate to very-severe depression, 79 (8.7%) for moderate to extremely-severe anxiety, 20 (2.2%) for moderate to extremely-severe stress, and 34 (3.8%) for moderate to severe levels of psychological distress. The commonest reported symptom was headache (32.3%), with a large number of participants (33.4%) reporting more than four symptoms. Participants who had experienced symptoms in the preceding month were more likely to be older, have pre-existing comorbidities and a positive screen for depression, anxiety, stress, and PTSD. After adjusting for age, gender and comorbidities, it was found that depression (OR 2.79, 95% CI 1.54-5.07, p = 0.001), anxiety (OR 2.18, 95% CI 1.36-3.48, p = 0.001), stress (OR 3.06, 95% CI 1.27-7.41, p = 0.13), and PTSD (OR 2.20, 95% CI 1.12-4.35, p = 0.023) remained significantly associated with the presence of physical symptoms experienced in the preceding month. Linear regression revealed that the presence of physical symptoms was associated with higher mean scores in the IES-R, DASS Anxiety, Stress and Depression subscales. CONCLUSIONS: Our study demonstrates a significant association between the prevalence of physical symptoms and psychological outcomes among healthcare workers during the COVID-19 outbreak. We postulate that this association may be bi-directional, and that timely psychological interventions for healthcare workers with physical symptoms should be considered once an infection has been excluded.

Headaches Associated With Personal Protective Equipment - A Cross-Sectional Study Among Frontline Healthcare Workers During COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease of pandemic proportions. Healthcare workers in Singapore working in high-risk areas were mandated to wear personal protective equipment (PPE) such as N95 face mask and protective eyewear while attending to patients. OBJECTIVES: We sought to determine the risk factors associated with the development of de novo PPE-associated headaches as well as the perceived impact of these headaches on their personal health and work performance. The impact of COVID-19 on pre-existing headache disorders was also investigated. METHODS: This is a cross-sectional study among healthcare workers at our tertiary institution who were working in high-risk hospital areas during COVID-19. All respondents completed a self-administered questionnaire. RESULTS: A total of 158 healthcare workers participated in the study. Majority [126/158 (77.8%)] were aged 21-35 years. Participants included nurses [102/158 (64.6%)], doctors [51/158 (32.3%)], and paramedical staff [5/158 (3.2%)]. Pre-existing primary headache diagnosis was present in about a third [46/158 (29.1%)] of respondents. Those based at the emergency department had higher average daily duration of combined PPE exposure compared to those working in isolation wards [7.0 (SD 2.2) vs 5.2 (SD 2.4) hours, P < .0001] or medical ICU [7.0 (SD 2.2) vs 2.2 (SD 0.41) hours, P < .0001]. Out of 158 respondents, 128 (81.0%) respondents developed de novo PPE-associated headaches. A pre-existing primary headache diagnosis (OR = 4.20, 95% CI 1.48-15.40; P = .030) and combined PPE usage for >4 hours per day (OR 3.91, 95% CI 1.35-11.31; P = .012) were independently associated with de novo PPE-associated headaches. Since COVID-19 outbreak, 42/46 (91.3%) of respondents with pre-existing headache diagnosis either "agreed" or "strongly agreed" that the increased PPE usage had affected the control of their background headaches, which affected their level of work performance. CONCLUSION: Most healthcare workers develop de novo PPE-associated headaches or exacerbation of their pre-existing headache disorders.

An unusual cause of acute ischemic stroke: Adult Onset Still's Disease.

Adult Onset Still's Disease (AOSD) is a systemic inflammatory disease of unknown aetiology. The usual manifestations of AOSD are spiking fevers, arthritis, and an evanescent salmon-pink rash, with neurological manifestations occasionally described. Stroke is a rare manifestation of AOSD and the exact mechanism for stroke in AOSD remains unknown, although it has been hypothesized to be secondary to thrombocytosis or vasculitis. We present a case where acute ischemic stroke secondary to a floating internal carotid artery thrombus was an early manifestation of AOSD. The patient also had prolonged high spiking fevers, significant leucocytosis, arthralgias and transaminitis. He responded well to a high dose of oral corticosteroids and was eventually started on anticoagulation for secondary stroke prevention. To our knowledge, this is the first described case of arterial thrombosis associated with AOSD. We postulate that thrombocytosis, vasculitis and hypercoagulability from the underlying inflammatory state may have contributed to the ischemic stroke.

A cross-sectional study on factors associated with poor work outcomes in patients with axial spondyloarthritis in Singapore.

AIM: Axial spondyloarthritis (axSpA) affects patients in the prime of their economic productivity. We aim to identify factors associated with poor work productivity in patients with axSpA in Singapore. METHODS: A cross-sectional study was performed in two tertiary centers in Singapore. Consecutive adult patients ≥21 years fulfilling Assessment in Spondyloarthritis International Society (ASAS) 2009 criteria for axSpA were recruited. Data on social demographics, clinical, treatment modalities and patient-reported outcome measures (PROMs) were collected. Work productivity was assessed by the Work Productivity and Activity Impairment scale (WPAI:SpA). Factors associated with presenteeism, absenteeism, work productivity loss and activity impairment were evaluated. RESULTS: A total of 156 patients with axSpA were included: 72.4% employed, 80.1% male, 86.5% Chinese, median (Q1:Q3) age and duration of illness 36.7 (28.7:47.9) years, and 6.3 (1.6:12.2) years respectively. The mean (SD) activity impairment was 28.2% (24.3%). Among employed patients, mean (SD) absenteeism, presenteeism and work productivity loss was 4.5% (13.7%), 24.9% (19.9%) and 27.6% (23.2%), respectively. In multivariable analysis, absenteeism was associated with disease duration (P = .02) and EuroQol-5D (EQ-5D) (P = .04). Presenteeism was associated with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥4 (P = .04), Bath Ankylosing Spondylitis Functional Index (BASFI) (P < .01) and EQ-5D (P = .02). Work productivity loss was associated with BASFI (P = .02) and EQ-5D (P < .01). Activity impairment was associated with age (P = .04), BASDAI ≥ 4 (P < .01), BASFI (P < .01), EQ-5D (P < .01). CONCLUSION: Active disease, reduced physical function and poorer quality of life are associated with reduced work productivity in patients with axSpA in Singapore. Addressing these factors can potentially improve work productivity in patients with axSpA.