Neurological involvement associated with SARS-CoV-2 infection is increasingly recognized. However, the specific characteristics and prevalence in pediatric patients remain unclear. The objective of this study was to describe the neurological involvement in a multinational cohort of hospitalized pediatric patients with SARS-CoV-2.

This was a multicenter observational study of children <18 years of age with confirmed SARS-CoV-2 infection or multisystemic inflammatory syndrome (MIS-C) and laboratory evidence of SARS-CoV-2 infection in children, admitted to 15 tertiary hospitals/healthcare centers in Canada, Costa Rica, and Iran February 2020–May 2021. Descriptive statistical analyses were performed and logistic regression was used to identify factors associated with neurological involvement.

One-hundred forty-seven (21%) of 697 hospitalized children with SARS-CoV-2 infection had neurological signs/symptoms. Headache (n = 103), encephalopathy (n = 28), and seizures (n = 30) were the most reported. Neurological signs/symptoms were significantly associated with ICU admission (OR: 1.71, 95% CI: 1.15–2.55; p = 0.008), satisfaction of MIS-C criteria (OR: 3.71, 95% CI: 2.46–5.59; p < 0.001), fever during hospitalization (OR: 2.15, 95% CI: 1.46–3.15; p < 0.001), and gastrointestinal involvement (OR: 2.31, 95% CI: 1.58–3.40; p < 0.001). Non-headache neurological manifestations were significantly associated with ICU admission (OR: 1.92, 95% CI: 1.08–3.42; p = 0.026), underlying neurological disorders (OR: 2.98, 95% CI: 1.49–5.97, p = 0.002), and a history of fever prior to hospital admission (OR: 2.76, 95% CI: 1.58–4.82; p < 0.001).

In this study, approximately 21% of hospitalized children with SARS-CoV-2 infection had neurological signs/symptoms. Future studies should focus on pathogenesis and long-term outcomes in these children.

Early and effective treatment of central nervous system (CNS) inflammatory disorders is vital to reduce neurologic morbidity and improve long-term outcomes in affected children. Rituximab is a B-cell-depleting monoclonal antibody whose off-label use for these disorders is funded in the province of Alberta, Canada, by the Short-Term Exceptional Drug Therapy (STEDT) program. This study describes the use of rituximab for pediatric CNS inflammatory disorders in Alberta.

Rituximab applications for CNS inflammatory indications in patients <18 years of age were identified from the STEDT database between January 1, 2012, and December 31, 2019. Patient information was linked to other provincial datasets including the Discharge Abstract Database, Pharmaceutical Information Network, and Provincial Laboratory data. Analysis was descriptive.

Fifty-one unique rituximab applications were identified, of which 50 were approved. New applications increased from one in 2012 to a high of 12 in 2018. The most common indication was autoimmune encephalitis without a specified antibody (n = 16, 31%). Most children were approved for a two-dose (n = 33, 66%) or four-dose (n = 16, 32%) induction regimen. Physician-reported outcomes were available for 24 patients, of whom 14 (58%) were felt to have fully met outcome targets.

The use of rituximab for pediatric CNS inflammatory disorders has increased, particularly for the indication of autoimmune encephalitis. This study identified significant heterogeneity in dosing practices and laboratory monitoring. Standardized protocols for the use of rituximab in these disorders and more robust outcome reporting will help better define the safety and efficacy of rituximab in this population

In patients with intracranial steno-occlusive disease (SOD), the risk of hemodynamic stroke depends on the poststenotic vasodilatory reserve. Cerebrovascular reactivity (CVR) is a test for vasodilatory reserve. We tested for vasodilatory reserve by using PETCO2 as the stressor, and Blood Oxygen Level Dependent (BOLD) MRI as a surrogate of blood flow. We correlate the CVR to the incidence of stroke after a 1-year follow-up in patients with symptomatic intracranial SOD.

In this retrospective study, 100 consecutive patients with symptomatic intracranial SOD that had undergone CVR testing were identified. CVR was measured as % BOLD MR signal intensity/mmHg PETCO2. All patients with normal CVR were treated with optimal medical therapy; those with abnormal CVR were offered revascularization where feasible. We determined the incidence of stroke at 1 year.

83 patients were included in the study. CVR was normal in 14 patients and impaired in 69 patients ipsilateral to the lesion. Of these, 53 underwent surgical revascularization. CVR and symptoms improved in 86% of the latter. The overall incidence of stroke was 4.8 % (4/83). All strokes occurred in patients with impaired CVR (4/69; 2/53 in the surgical group, all in the nonrevascularized hemisphere), and none in patients with normal CVR (0/14).

Our study confirms that CO2-BOLD MRI CVR can be used as a brain stress test for the assessment of cerebrovascular reserve. Impaired CVR is associated with a higher incidence of stroke and normal CVR despite significant stenosis is associated with a low risk for stroke.

Cognitive and functional impairment after stroke are common, but the relation between cognitive and functional decline after stroke is not well studied.

We used the comprehensive cohort in the Canadian Longitudinal Study on Aging to identify those with prior stroke, and we calculated reliable cognitive change scores from baseline to follow-up for the memory and executive domains. Functional decline was defined as an increase in the number of dependent daily activities. Using formal mediation analysis, we tested the presence and degree of mediation of the association between stroke and functional decline by cognitive decline.

There were 22,648 individuals with memory change scores (325 with stroke) and 17,613 individuals with executive change scores (241 with stroke). History of stroke was significantly associated with memory decline (−0.26 standard deviations, 95% CI −0.33 to −0.19), executive decline (−0.22, 95% CI −0.36 to −0.09), and new functional impairment (adjusted odds ratio 2.31, 95% CI 1.80–2.97) over a median of 3-year follow-up. Cognitive decline was a significant mediator of functional decline. Memory decline mediated only 5% of the relationship, whereas executive and overall cognitive decline mediated 13% and 22%, respectively.

Cognitive decline is a mediator of the association between prior stroke and functional decline; consequently, strategies to delay, attenuate, or prevent cognitive decline after stroke may be important to preserving long-term functional status.

Cardiac sources of emboli can be identified by transthoracic echocardiogram (TTE). The Canadian Best Practice Guidelines recommend routine use of TTE in the initial workup of ischemic stroke when an embolic source is suspected. However, TTEs are commonly ordered for all patients despite insufficient evidence to justify cost-effectiveness. We aim to evaluate the TTE ordering pattern in the initial workup of ischemic stroke at a regional Stroke Center in Central South Ontario and determine the proportion of studies which led to a change in management and affected length of stay (LOS).

Hospital records of 520 patients with a discharge diagnosis of TIA or ischemic stroke between October 2016 and June 2017 were reviewed to gather information

477 patients admitted for TIA or ischemic stroke met inclusion criteria. 67.9% received TTE, out of which 6.0% had findings of cardiac sources of emboli including left ventricular thrombus, atrial septal aneurysm, PFO, atrial myxoma, and valvular vegetation. 2.5% of all TTE findings led to change in medical management. The median LOS of patients who underwent TTE was 2 days longer (p < 0.00001).

TTE in the initial workup of TIA or ischemic stroke remains common practice. The yield of TTEs is low, and the proportion of studies that lead to changes in medical management is minimal. TTE completion was associated with increased LOS and may result in increased healthcare spending; however, additional factors prolonging the LOS could not be excluded.

It is unknown if the COVID-19 pandemic and public health measures had an immediate impact on stroke subtypes and etiologies in patients not infected with COVID-19. We aimed to evaluate if the proportion of non-COVID-19-related stroke subtypes (ischemic vs. hemorrhagic) and etiologies (cardioembolic, atherosclerosis, small vessel disease, and others) during the pandemic’s first wave were different from prepandemic.

For this retrospective cohort study, we included patients without COVID-19 with ischemic or hemorrhagic stroke at two large Canadian stroke centers between March–May 2019 (prepandemic cohort) and March–May 2020 (pandemic cohort). Proportions of stroke subtypes and etiologies were compared between cohorts using chi-square tests.

The prepandemic cohort consisted of 234 stroke patients and the pandemic cohort of 207 stroke patients. There were no major differences in baseline characteristics. The proportions of ischemic versus hemorrhagic stroke were similar (ischemic stroke: 77% prepandemic vs. 75% pandemic; hemorrhagic stroke:12% prepandemic vs. 14% pandemic; p > 0.05). There were no differences in etiologies, except for a decreased proportion of ischemic stroke due to atherosclerosis in the pandemic cohort (26% prepandemic vs. 15% pandemic; difference: 10.6%, 95%CI: 1.4-19.7; p = 0.03). Notably, during the pandemic, the cause of ischemic stroke was more often unknown because of incomplete work-up (13.3% prepandemic vs. 28.2% pandemic, difference: 14.9%, 95%-CI: 5.7–24.2; p = <0.01).

In this study, the pandemic had no clear effect on stroke subtypes and etiologies suggesting a limited impact of the pandemic on stroke triggers. However, the shift from atherosclerosis toward other causes warrants further exploration.

Concussion affects 1.2% of the population annually; rural regions and children have higher rates of concussion.

Using administrative health care linked databases, all residents of Ontario with a physician diagnosed concussion were identified using ICD-9 code 850 or ICD-10 code S06. Cases were tracked for 2 years for concussion-related health care utilization with relevant specialist physicians (i.e., neurology, otolaryngology, physiatry, psychiatry, ophthalmology). Billing codes, specialist codes, and time from index to visit were analyzed. Factors associated with increased specialist visits were also examined.

In total, 1,022,588 cases were identified between 2008 and 2014 with 2 years of post-concussion health care utilization available. Follow-up by physician within 3 days of injury occurred in only 14% of cases. Mean time between ED diagnosis and follow-up by a physician was 83.9 days, whereas for rural regions it was >100 days. About half of adults (51.9%) and children (50.3%) had at least 1 specialist visit following concussion. Mean time between injury and first specialist visit was 203.8 (SD 192.9) days for adults, 213.5 (SD 201.0) days for rural adults, and 276.0 (SD 202.6) days for children. There were 67,420 neurology visits, 70,404 psychiatry visits, 13,571 neurosurgery visits, 19,780 physiatry visits, 101,788 ENT visits, and 103,417 ophthalmology visits in the 2 years tracking period. Factors associated with more specialist use included age > 18 years, urban residence, and pre-injury psychiatric history.

There are discrepancies in post-concussion health care utilization based on age group and rural/urban residence. Addressing these risk factors could improve concussion care access.

Up to 30% of patients with Guillain–Barré syndrome require mechanical ventilation and 5% die due to acute complications of mechanical ventilation. There is a considerable group of patients that will need prolonged mechanical ventilation (considered as >14 days) and should be considered for early tracheostomy. The objective of this study is to identify risk factors for prolonged mechanical ventilation.

We prospectively analyzed patients with Guillain–Barré diagnosis with versus without prolonged mechanical ventilation. We considered clinical and electrophysiological characteristics and analyzed factors associated with prolonged mechanical ventilation.

Three hundred and three patients were included; 29% required mechanical ventilation. When comparing the groups, patients with prolonged invasive mechanical ventilation (IMV) have a lower score on the Medical Research Council score (19.5 ± 16.2 vs 27.4 ± 17.5, p = 0.03) and a higher frequency of dysautonomia (42.3% vs 19.4%, p = 0.037), as well as lower amplitudes of the distal compound muscle action potential (CMAP) of the median nerve [0.37 (RIQ 0.07–2.25) vs. 3.9 (RIQ1.2–6.4), p = <0.001] and ulnar nerve [0.37 (RIQ0.0–3.72) vs 1.5 (RIQ0.3–6.6), p = <0.001], and higher frequency of severe axonal damage in these nerves (distal CMAP ≤ 1.0 mV). Through binary logistic regression, severe axonal degeneration of the median nerve is an independent risk factor for prolonged IMV OR 4.9 (95%CI 1.1–21.5) p = 0.03, AUC of 0.774, (95%CI 0.66–0.88), p = < 0.001.

Severe median nerve damage is an independent risk factor for prolonged mechanical ventilation.

Pathophysiology of levodopa-induced dyskinesia (LID) remains obscure. Increased dopamine metabolism due to prolonged levodopa treatment can exacerbate oxidative damage and neuroinflammatory pathology in Parkinson’s disease (PD). Association of novel peripheral markers with LID severity might provide insight into LID pathomechanisms.

We aimed to study specific peripheral blood inflammatory-oxidative markers in LID patients and investigate their association with clinical severity of LID.

Motor, non-motor and cognitive changes in PD with and without LID compared to healthy-matched controls were identified. Within the same cohort, inflammatory marker (sLAG3, TOLLIP, NLRP3 and IL-1β) levels and antioxidant enzyme activities were determined by ELISA and spectrophotometric methods.

LID patients showed distinctly upregulated TOLLIP, IL-1β levels with significant diminution of antioxidant activity compared to controls. Significant negative association of cognitive markers with oxidative changes was also observed.

To our understanding, this is the first study that indicates the involvement of toll-like receptor-mediated distinct and low-grade inflammatory activation in LID pathophysiology.