Intravenous Thrombolysis for Acute Ischemic Stroke due to Cervical Internal Carotid Artery Occlusion.

BACKGROUND: Internal carotid artery (ICA) occlusions are poorly responsive to intravenous thrombolysis with tissue plasminogen activator (IV-tPA) in acute ischemic stroke (AIS). Most study populations have combined intracranial and extracranial ICA occlusions for analysis; few have studied purely cervical ICA occlusions. We evaluated AIS patients with acute cervical ICA occlusion treated with IV-tPA to identify predictors of outcomes. METHODS: We studied 550 consecutive patients with AIS who received IV-tPA and identified 100 with pure acute cervical ICA occlusion. We evaluated the associations of vascular risk factors, National Institutes of Health Stroke Scale (NIHSS) score, and leptomeningeal collateral vessel status via 3 different grading systems, with functional recovery at 90 days, mortality, recanalization of the primary occlusion, and symptomatic intracranial hemorrhage (SICH). Modified Rankin Scale score 0-1 was defined as an excellent outcome. RESULTS: The 100 patients had mean age of 67.8 (range 32-96) and median NIHSS score of 19 (range 4-33). Excellent outcomes were observed in 27% of the patients, SICH in 8%, and mortality in 21%. Up to 54% of the patients achieved recanalization at 24 hours. On ordinal regression, good collaterals showed a significant shift in favorable outcomes by Maas, Tan, or ASPECTS collateral grading systems. On multivariate analysis, good collaterals also showed reduced mortality (OR .721, 95% CI .588-.888, P = .002) and a trend to less SICH (OR .81, 95% CI .65-1.007, P = .058). Interestingly, faster treatment was also associated with favorable functional recovery (OR 1.028 per minute, 95% CI 1.010-1.047, P = .001). CONCLUSIONS: Improved outcomes are seen in patients with early acute cervical ICA occlusion and better collateral circulation. This could be a valuable biomarker for decision making.

Exploring new healthcare professionals' roles through interprofessional education.

This article presents findings from a simulation-based interprofessional education (IPE) program involving trainee advanced practice nurses (APNs) and internal medicine residents (IMRs) based in Singapore. Trainee APNs and IMRs participated in a semester-long series of high-fidelity simulations of medical emergencies. Learners' attitudes toward the IPE intervention were assessed using validated Likert scaled surveys and written comments. Overall satisfaction was high among learners, with strongly positive attitudes toward teamwork, collaboration and patient centredness. Of most interest, written comments highlight the utility of IPE in defining the professional scope and boundaries of APNs. Comments from both professions observed that participation in the IPE scenarios greatly aided their understanding of the scope and role of APN's practice within the health care team. This aspect of IPE may find further application in other similarly novel roles in healthcare.

Atypical Bickerstaff brainstem encephalitis: ataxic hypersomnolence without ophthalmoplegia.

OBJECTIVE: Clinical and immunological evaluation of 'incomplete' Bickerstaff brainstem encephalitis (BBE). METHODS: We studied two patients with postinfectious brainstem syndromes who presented at National University Hospital Singapore. Laboratory work-up included measurement of antiganglioside antibodies. RESULTS: Both patients displayed hypersomnolence and cerebellar-like ataxia in the absence of external ophthalmoplegia and carried high serum titres of IgG anti-GQ1b antibodies, strongly indicative of BBE. CONCLUSIONS: Ophthalmoplegia can be absent or incomplete in BBE, and the absence of this clinical feature should not exclude BBE from the clinicians' differential. Such cases of incomplete BBE could be defined as 'ataxic hypersomnolence without ophthalmoplegia'.

COVID-19 infection after two doses of SARS-CoV-2 mRNA vaccine in multiple sclerosis, AQP4-antibody NMOSD and MOGAD.

BACKGROUND: In pre-vaccinated people with multiple sclerosis (MS), certain disease-modifying therapies (DMTs), particularly the anti-CD20 treatments, appear to be associated with an increased risk of COVID-19 infection and indeed with severe infection. It is still not known if such observations extend to vaccinated individuals and there have been considerably fewer studies in aquaporin-4-antibody neuromyelitis optica spectrum disorder (AQP4-NMOSD) and myelin oligodendrocyte glycoprotein-antibody associated disease (MOGAD) patients. In this study, we investigated the rates of symptomatic COVID-19 infection in adult patients with MS, AQP4-NMOSD and MOGAD who had received 2 doses of SARS-CoV-2 mRNA vaccine. METHODS: This was a prospective observational study conducted at the 2 main neuroimmunology referral centres in Singapore. Only patients on active follow-up were recruited to ensure robust data collection. Data on demographics, disease history, DMTs and SARS-CoV-2 mRNA vaccinations were recorded, and for those infected with COVID-19, data on COVID-19 infection was collected. RESULTS: Nineteen (13 MS, 5 AQP4-NMOSD, 1 MOGAD) out of 365 (231 MS, 106 AQP4-NMOSD, 28 MOGAD) patients had COVID-19 infection despite 2 doses of SARS-CoV-2 mRNA vaccine. Amongst the infected patients, 11 patients were on DMTs (3 rituximab, 2 interferons, 1 azathioprine, 1 mycophenolate, 1 prednisolone, 1 cladribine, 1 alemtuzumab, 1 fingolimod), while 8 patients were untreated. The crude infection rate was calculated using time-at-risk analysis, revealing that rituximab had the highest infection rate amongst all the DMTs. A lower crude infection rate was observed in patients who received a third vaccination. The majority of infections were mild and no patients required oxygen supplementation. CONCLUSION: Our findings suggest that patients on rituximab are still at risk of COVID-19 infection after 2 vaccinations and the receipt of a third vaccination may help to prevent infection. Future large scale studies will be required to better delineate the infection risk of different DMTs after the second and subsequent vaccinations.

Disentangling etiologies of CNS infections in Singapore using multiple correspondence analysis and random forest.

Central nervous system (CNS) infections cause substantial morbidity and mortality worldwide, with mounting concern about new and emerging neurologic infections. Stratifying etiologies based on initial clinical and laboratory data would facilitate etiology-based treatment rather than relying on empirical treatment. Here, we report the epidemiology and clinical outcomes of patients with CNS infections from a prospective surveillance study that took place between 2013 and 2016 in Singapore. Using multiple correspondence analysis and random forest, we analyzed the link between clinical presentation, laboratory results, outcome and etiology. Of 199 patients, etiology was identified as infectious in 110 (55.3%, 95%-CI 48.3-62.0), immune-mediated in 10 (5.0%, 95%-CI 2.8-9.0), and unknown in 79 patients (39.7%, 95%-CI 33.2-46.6). The initial presenting clinical features were associated with the prognosis at 2 weeks, while laboratory-related parameters were related to the etiology of CNS disease. The parameters measured were helpful to stratify etiologies in broad categories, but were not able to discriminate completely between all the etiologies. Our results suggest that while prognosis of CNS is clearly related to the initial clinical presentation, pinpointing etiology remains challenging. Bio-computational methods which identify patterns in complex datasets may help to supplement CNS infection diagnostic and prognostic decisions.

The adult patient with headache.

Headaches are common in primary care. For safe assessment and management of the patient with headache, a focused history and physical examination are important to identify secondary headache, and find out whether an immediate referral to the emergency department or a non-emergent referral to the neurologist is warranted. The majority of patients with primary headache may be safely managed in the outpatient setting. Key steps include proper categorisation of the primary headache, attention to lifestyle and psychosocial factors, prescription of analgesics for acute pain relief, and the use of preventive medication when indicated. The patient with a cluster headache, a headache of uncertain diagnosis and/or poor response to preventive strategies or a migraine with persistent aura, or a headache with associated motor weakness, should be referred to a neurologist. Secondary headache and the diagnosis of medication overuse headache should be considered in a patient on long-term analgesics with unremitting headache.

Cladribine: Off-label disease modification for people with multiple sclerosis in resource-poor settings?

BACKGROUND: A considerable number of people with multiple sclerosis (pwMS) live in low- and middle-income countries (LMIC), where lack of resource adversely affects access to effective disease-modifying treatment. OBJECTIVE: The objective of this commentary is to propose a useful cost-effective disease-modifying treatment option for pwMS in LMIC with potential high efficacy and high convenience to the pwMS and treating physician.Viewpoint: We propose using generic 2-chloro-2'-deoxyadenosine (cladribine), a small molecule licensed for treatment of people with hairy cell leukaemia, as a solution of this significant equity imbalance. Cladribine has been shown in phase II and III trials to be a highly effective disease-modifying treatment for pwMS, and its adverse effect profile is comparable with any DMT currently licensed in high-income economies where an oral preparation has recently been licensed by the European Medicines Agency. CONCLUSION: Our viewpoint takes into account experience we have gathered over the past three years in the use of generic cladribine to treat pwMS. Whilst here we focus on MS, there is significant potential for use of cladribine in other conditions that could benefit from its mechanism of action.

A study of subtle blood brain barrier disruption in a placebo-controlled trial of natalizumab in relapsing remitting multiple sclerosis.

Natalizumab, an anti-alpha4 integrin antibody, significantly reduces the number of visibly enhancing multiple sclerosis (MS) lesions. In this substudy of a 2-year trial of natalizumab monotherapy versus placebo, contrast-enhanced imaging investigated for subtle blood brain barrier (BBB) leakage in relapsing remitting (RRMS) patients, and whether such leakage is modified by natalizumab. After 24 weeks on treatment, 40 patients from 3 centres (27 on natalizumab and 13 on placebo) were studied. T1 weighted images were obtained before and at set timepoints up to 46 minutes after gadolinium (Gd)-DTPA (0.3 mmol/kg to 18 patients, 0.15 mmol/kg to 22). Paired regions of interest were placed around non-enhancing lesions and contralateral normal appearing white matter (NAWM). BBB leakage was inferred through post-Gd T1 weighted signal intensity (SI) change. SI change was greater in T2 non-enhancing lesions than paired NAWM at all timepoints (P<0.005), indicating BBB leakage in lesions. No significant difference in inferred BBB leakage was observed between treatment arms as measured by SI change of lesions (P>0.05 for all timepoints, joint test P=0.24), or in SI change of NAWM (joint test P=0.37). T1 hypointense and isointense lesions exhibited similar SI changes (joint test P=0.12). There is evidence of a subtle BBB leakage within visibly non-enhancing lesions in RRMS that was not modified by alpha4 integrin blockade in this substudy cohort.

Outpatient management of transient ischaemic attack.

Stroke is a significant cause of death and disability in Singapore; in 2014, it was the fourth most common cause of death. Transient ischaemic attack (TIA) is defined as a transient episode of neurological dysfunction caused by focal brain, spinal cord or retinal ischaemia without evidence of acute infarction. The diagnosis of TIA/acute stroke needs to be considered in all patients who present with sudden focal neurological dysfunction. Prompt referral for assessment, neuroimaging and intervention provides the best chance for neurological recovery and/or minimising further neurological damage. Primary care physicians have a crucial role in TIA/stroke prevention and management. This includes referring patients with suspected acute TIA/stroke to hospitals with stroke treatment facilities immediately; managing the modifiable risk factors of cerebral ischaemia; continuing prescription of antiplatelet agents and/or anticoagulation where indicated; and teaching patients to recognise and respond to suspected cerebral ischaemia using the FAST (face, arm, speech, time) acronym.

How temporal evolution of intracranial collaterals in acute stroke affects clinical outcomes.

OBJECTIVE: We compared intracranial collaterals on pretreatment and day 2 brain CT angiograms (CTA) to assess their evolution and relationship with functional outcomes in acute ischemic stroke (AIS) patients treated with IV tissue plasminogen activator (tPA). METHODS: Consecutive AIS patients who underwent pretreatment and day 2 CTA and received IV tPA during 2010-2013 were included. Collaterals were evaluated by 2 independent neuroradiologists using 3 predefined criteria: the Miteff system, the Maas system, and 20-point collateral scale by the Alberta Stroke Program Early CT Score methodology. We stratified our cohort by baseline pre-tPA state of their collaterals and by recanalization status of the primary vessel for analysis. Good outcomes at 3 months were defined by a modified Rankin Scale score of 0-1. RESULTS: This study included 209 patients. Delayed collateral recruitment by any grading system was not associated with good outcomes. All 3 scoring systems showed that collateral recruitment on the follow-up CTA from a baseline poor collateral state was significantly associated with poor outcome and increased bleeding risk. When the primary vessel remained persistently occluded, collateral recruitment was significantly associated with worse outcomes. Interestingly, collateral recruitment was significantly associated with increased mortality in 2 of the 3 grading systems. CONCLUSIONS: Not all collateral recruitment is beneficial; delayed collateral recruitment may be different from early recruitment and can result in worse outcomes and higher mortality. Prethrombolysis collateral status and recanalization are determinants of how intracranial collateral evolution affects functional outcomes.

Acute-onset chronic inflammatory demyelinating polyneuropathy with focal segmental glomerulosclerosis.

Inflammatory neuropathies have been reported to occur in association with nephrotic syndrome. Their underlying immuno-pathogenic mechanisms remain unknown. A 50-year-old woman concurrently presented with acute-onset chronic inflammatory demyelinating polyneuropathy and nephrotic syndrome secondary to focal segmental glomerulosclerosis. Both neuropathy and proteinuria improved after plasma exchange and steroids. Literature review of cases of concurrent inflammatory neuropathies and nephrotic syndrome revealed similar neuro-renal presentations. This neuro-renal condition may be mediated by autoantibodies targeting myelin and podocytes.