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.

Incidence of Cerebral Venous Thrombosis Following SARS-CoV-2 Infection vs mRNA SARS-CoV-2 Vaccination in Singapore.

Importance: Reports of cerebral venous thrombosis (CVT) after messenger RNA (mRNA)-based SARS-CoV-2 vaccination has caused safety concerns, but CVT is also known to occur after SARS-CoV-2 infection. Comparing the relative incidence of CVT after infection vs vaccination may provide a better perspective of this complication. Objective: To compare the incidence rates and clinical characteristics of CVT following either SARS-CoV-2 infection or mRNA-based SARS-CoV-2 vaccines. Design, Setting, and Participants: Between January 23, 2020, and August 3, 2021, this observational cohort study was conducted at all public acute hospitals in Singapore, where patients hospitalized with CVT within 6 weeks of SARS-CoV-2 infection or after mRNA-based SARS-CoV-2 vaccination (BNT162b2 [Pfizer-BioNTech] or mRNA-1273 [Moderna]) were identified. Diagnosis of SARS-CoV-2 infection was based on quantitative reverse transcription-polymerase chain reaction or positive serology. National SARS-CoV-2 infection data were obtained from the National Centre for Infectious Disease, Singapore, and vaccination data were obtained from the National Immunisation Registry, Singapore. Exposures: SARS-CoV-2 infection or mRNA-based SARS-CoV-2 vaccines. Main Outcomes and Measures: Clinical characteristics, crude incidence rate (IR), and incidence rate ratio (IRR) of CVT after SARS-CoV-2 infection and after mRNA SARS-CoV-2 vaccination. Results: Among 62 447 individuals diagnosed with SARS-CoV-2 infections included in this study, 58 989 (94.5%) were male; the median (range) age was 34 (0-102) years; 6 CVT cases were identified (all were male; median [range] age was 33.5 [27-40] years). Among 3 006 662 individuals who received at least 1 dose of mRNA-based SARS-CoV-2 vaccine, 1 626 623 (54.1%) were male; the median (range) age was 50 (12-121) years; 9 CVT cases were identified (7 male individuals [77.8%]; median [range] age: 60 [46-76] years). The crude IR of CVT after SARS-CoV-2 infections was 83.3 per 100 000 person-years (95% CI, 30.6-181.2 per 100 000 person-years) and 2.59 per 100 000 person-years (95% CI, 1.19-4.92 per 100 000 person-years) after mRNA-based SARS-CoV-2 vaccination. Six (66.7%) received BNT162b2 (Pfizer-BioNTech) vaccine and 3 (33.3%) received mRNA-1273 (Moderna) vaccine. The crude IRR of CVT hospitalizations with SARS-CoV-2 infection compared with those who received mRNA SARS-CoV-2 vaccination was 32.1 (95% CI, 9.40-101; P < .001). Conclusions and Relevance: The incidence rate of CVT after SARS-CoV-2 infection was significantly higher compared with after mRNA-based SARS-CoV-2 vaccination. CVT remained rare after mRNA-based SARS-CoV-2 vaccines, reinforcing its safety.

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.

Acute Ischemic Stroke During the Convalescent Phase of Asymptomatic COVID-2019 Infection in Men.

Importance: Acute ischemic stroke (AIS) is a known neurological complication in patients with respiratory symptoms of COVID-19 infection. However, AIS has not been described as a late sequelae in patients without respiratory symptoms of COVID-19. Objective: To assess AIS experienced by adults 50 years or younger in the convalescent phase of asymptomatic COVID-19 infection. Design, Setting, and Participants: This case series prospectively identified consecutive male patients who received care for AIS from public health hospitals in Singapore between May 21, 2020, and October 14, 2020. All of these patients had laboratory-confirmed asymptomatic COVID-19 infection based on a positive SARS-CoV-2 serological (antibodies) test result. These patients were individuals from South Asian countries (India and Bangladesh) who were working in Singapore and living in dormitories. The total number of COVID-19 cases (54 485) in the worker dormitory population was the population at risk. Patients with ongoing respiratory symptoms or positive SARS-CoV-2 serological test results confirmed through reverse transcriptase-polymerase chain reaction nasopharyngeal swabs were excluded. Main Outcomes and Measures: Clinical course, imaging, and laboratory findings were retrieved from the electronic medical records of each participating hospital. The incidence rate of AIS in the case series was compared with that of a historical age-, sex-, and ethnicity-matched national cohort. Results: A total of 18 male patients, with a median (range) age of 41 (35-50) years and South Asian ethnicity, were included. The median (range) time from a positive serological test result to AIS was 54.5 (0-130) days. The median (range) National Institutes of Health Stroke Scale score was 5 (1-25). Ten patients (56%) presented with a large vessel occlusion, of whom 6 patients underwent intravenous thrombolysis and/or endovascular therapy. Only 3 patients (17%) had a possible cardiac source of embolus. The estimated annual incidence rate of AIS was 82.6 cases per 100 000 people in this study compared with 38.2 cases per 100 000 people in the historical age-, sex-, and ethnicity-matched cohort (rate ratio, 2.16; 95% CI, 1.36-3.48; P < .001). Conclusions and Relevance: This case series suggests that the risk for AIS is higher in adults 50 years or younger during the convalescent period of a COVID-19 infection without respiratory symptoms. Acute ischemic stroke could be part of the next wave of complications of COVID-19, and stroke units should be on alert and use serological testing, especially in younger patients or in the absence of traditional risk factors.

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.

Topiramate for migraine prophylaxis among Chinese population.

We evaluated the efficacy and safety of topiramate for migraine prophylaxis among Chinese patients in a multicenter prospective observational study. We found that topiramate at low doses was effective in preventing migraine headache in Chinese patients and was generally well tolerated. There was no difference in baseline headache frequency or intensity between responders and nonresponders.

Mechanisms of antibiotic neurotoxicity in renal failure.

Neurological complications of antibiotics are relatively common in renal failure. Central nervous system neurotoxicity due to penicillin and beta-lactam antibiotics is best documented with fewer accounts of ototoxicity, peripheral nerve toxicity and neuromuscular blockade. In the context of risk stratification, the goal of this review is to explore the mosaic of factors in renal impairment that may contribute to susceptibility to antibiotic neurotoxicity. Improved knowledge of the pathogenesis of these formidable adverse events among the renal failure subjects should help prevent antibiotic neurotoxicity in the future.

Influence of emergency room fee on acute stroke presentation in a public hospital in Hong Kong.

A new system of emergency room fee-for-service was recently introduced at public hospitals in Hong Kong. A prospective observational study was undertaken to investigate the effects of the emergency room consultation fee system on presentation delay of acute stroke patients and evaluation of timing of patient presentation with acute stroke. We reviewed 2 specified periods (2-month interval each) before and after the consultation fee system at a public hospital. Primary outcome measures were time from onset of stroke symptoms to arrival at hospital, and predictors of such a time delay. A total of 173 subjects were recruited before institution of the consultation fee system, and 189 after inception of the new system. The mean age was 71 years. The median delay between symptom onset and arrival at hospital was 9 h. Acute ischemic stroke accounted for 91% of the stroke diagnoses. The median baseline NIHSS score measured 6. The median delay for patients before the emergency room consultation fee system was 9.7 h, compared with 8.4 h after introduction of the consultation fee (p = 0.66). At presentation, patients admitted during the consultation fee system were significantly more likely to be unconscious and be in a worse functional premorbid state. We found no difference in the frequency of general practitioner contact between the 2 study periods. Overall, univariate analyses showed that patient age, baseline NIHSS score, consciousness level upon arrival at the emergency department and premorbid ambulatory status were significant factors associated with the timing of presentation after acute stroke. A multivariate linear regression model demonstrated two independent factors: patient age younger than 70 years was independently related to presentation delay, whereas severity of stroke as indicated by unconsciousness upon arrival was associated with shorter delay. While we demonstrated no delays in acute stroke presentation accrued from enactment of the emergency room fee, physicians should endeavor to further explore strategies of reducing the late presentation of acute stroke.

Vagus nerve stimulation for refractory epilepsy: long term efficacy and side-effects.

BACKGROUND: In general vagus nerve stimulation (VNS) can serve as an adjunctive treatment for patients with refractory partial-onset seizures. And we evaluated the long-term efficacy and safety of VNS in a group of Chinese patients with refractory epilepsy. METHODS: Of 127 patients with refractory epilepsy, 13 patients who were not eligible for surgical intervention were implanted with the Cyberonics VNS system. Seizure frequency, physical examination and side effects profile were recorded at follow-up visits for a minimum of 18 months. RESULTS: Mean duration of treatment was 47.4 months, and the longest follow-up period was 71 months. Mean baseline seizure frequency was 26.6 seizures per month. The mean percentage reductions in convulsions were 33.2%, 47.1% and 40.0% at 6, 12 and 18 months, respectively. One patient became seizure free, and six (46%) had 50% or more reduction in seizure frequency. Response was poor (< 20% reduction) in five patients (39%). Side effects were uncommon. CONCLUSIONS: The effectiveness of VNS was sustained and was well tolerated but benefited only a sub-group of patients with intractable convulsions.

Retrospective review of neurotoxicity induced by cefepime and ceftazidime.

We reviewed 42 cases of cefepime-induced neurotoxicity and 12 cases of ceftazidime-induced neurotoxicity from the literature and our institution. Clinical characteristics and timing of diagnosis were examined. Common findings were confusion with temporospatial disorientation (96% of patients), myoclonus (33%), and seizures (13%). These neurologic disorders frequently are encountered in uremic and elderly patients, who often are in a confused state when they visit their physician. The risk of delayed diagnosis was greater with cefepime than ceftazidime neurotoxicity. The median interval between symptom onset and diagnosis of cefepime versus ceftazidime neurotoxicity was 5 and 3 days, respectively (p=0.005). Delayed diagnosis of cefepime neurotoxicity may be due to lack of awareness of the adverse effect. Data gathered since these two broad-spectrum antibiotics were first marketed underscore the potential for neurologic adverse events secondary to their administration. Thus, clinicians' awareness must be increased so that the time between symptom onset and diagnosis can be reduced.