Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) refractory to conventional therapy can lead to marked disability and represents a therapeutic challenge.

To report five cases of treatment-refractory disabling CIDP treated with autologous hematopoietic stem cell transplantation (AHSCT).

This was a retrospective cohort study from a tertiary care referral center for both neuromuscular disease and AHSCT. Patients with CIDP treated with AHSCT between 2008 and 2020 were included. All patients had major persistent and disabling neuropathic deficits despite combinations of intensive immunosuppressive therapy. The primary outcome measures were: Medical Research Council sum score, Overall Neuropathy Limitations Scale and requirement for ongoing CIDP immunotherapy after transplantation. We also analyzed safety outcomes by documenting all severe AHSCT-related complications.

Five patients with refractory CIDP underwent AHSCT. Three were classified as manifesting a typical syndrome, two were classified as the multifocal Lewis Sumner variant. The mean age at time of CIDP diagnosis was 33.4 years (range 24–46 years), with a median delay of 46 months (range 21–135 months) between diagnosis and AHSCT. The median follow-up period was 41 months. All five patients were able to wean off CIDP-related immunotherapy. Marked improvements in Medical Research Council scale and overall Neuropathy Limitations Scale were noted in 4/5 patients. One patient with longstanding neurogenic atrophy showed no improvement in disability scales. There were no treatment-related deaths or critical illnesses.

AHSCT can achieve marked sustained clinical improvement of refractory CIDP and may allow for weaning off long-term complex immunotherapies.

Myasthenia gravis (MG) is an autoimmune disorder that frequently affects young women of reproductive age. The multidirectional interplay between MG, pregnancy, and fetal health poses a complex scenario for pregnant women with MG and the healthcare team. Here, we reviewed our local experience with MG, pregnancy, and outcomes.

We performed a retrospective chart review of patients with MG attending the Prosserman Family Neuromuscular Clinic from 2001 to 2019 and who were referred to a high-risk pregnancy clinic. MG status was defined as stable, better, or worse. Information was collected on the delivery route, pregnancy, and neonatal complications.

We identified 20 women with MG for a total of 28 pregnancies. Worsening was observed in 50% of pregnancies: 18% during pregnancy, 25% following delivery, and 7% during both. 66.7% of patients with MG duration of 2 years or less had worsening during pregnancy. Three patients who stopped immunosuppressive treatment during pregnancy worsened and one had a crisis. C-section was done in 29% of pregnancies. The rate of delivery complications was 7% and of neonatal MG was 7%.

A high proportion of MG patients worsened during pregnancy, particularly those with disease duration less than 2 years, and those who discontinued immunosuppression during pregnancy. However, pregnancy was largely unaffected, rate of neonatal MG was low, frequencies of C-section, delivery complications, and premature births were similar to the general population. While the study has limitations due to the retrospective nature, these insights provide some guidance when counseling young myasthenic women about family planning.

Medical assistance in dying (MAiD), also known as physician-assisted death, is currently legal in several locations across the globe. Brain cancer or its treatments can lead to cognitive impairment, which can impact decision-making capacity for MAiD.

We sought to explore neuro-oncology clinicians’ attitudes and perspectives on MAiD, including interpretation of decision-making capacity for patient MAiD eligibility.

An online survey was distributed to members of national and international neuro-oncology societies. We asked questions about decision-making capacity and MAiD, in part using hypothetical patient scenarios. Multiple choice and free-text responses were captured.

There were 125 survey respondents. Impaired cognition was identified as the most important factor that would signal a decline in patient capacity. At least 26% of survey respondents had moral objections to MAiD. Respondents thought that different hypothetical patients had capacity to make a decision about MAiD (range 18%–58%). In other hypothetical scenarios, fewer clinicians were willing to support a MAiD decision for a patient with an oligodendroglioma (26%) vs. glioblastoma (41%–70%, depending on the scenario). Time since diagnosis, performance status, and patient age seemed to affect support for MAiD decisions (Fisher’s exact P-values 0.007, < 0.001, and 0.049, respectively).

While there are differing opinions on the moral permissibility of MAiD in general and for neuro-oncology patients, most clinicians agree that capacity must be assessed carefully before a decision is made. End-of-life discussions should happen early, before the capacity is lost. Our results can inform assessments of patient capacity in jurisdictions where MAiD is legal.

We assessed long-term incidence and prevalence trends of dementia and parkinsonism across major ethnic and immigrant groups in Ontario.

Linking administrative databases, we established two cohorts (dementia 2001–2014 and parkinsonism 2001–2015) of all residents aged 20 to 100 years with incident diagnosis of dementia (N = 387,937) or parkinsonism (N = 59,617). We calculated age- and sex-standardized incidence and prevalence of dementia and parkinsonism by immigrant status and ethnic groups (Chinese, South Asian, and the General Population). We assessed incidence and prevalence trends using Poisson regression and Cochran–Armitage trend tests.

Across selected ethnic groups, dementia incidence and prevalence were higher in long-term residents than recent or longer-term immigrants from 2001 to 2014. During this period, age- and sex-standardized incidence of dementia in Chinese, South Asian, and the General Population increased, respectively, among longer-term immigrants (by 41%, 58%, and 42%) and long-term residents (28%, 7%, and 4%), and to a lesser degree among recent immigrants. The small number of cases precluded us from assessing parkinsonism incidence trends. For Chinese, South Asian, and the General Population, respectively, prevalence of dementia and parkinsonism modestly increased over time among recent immigrants but significantly increased among longer-term immigrants (dementia: 134%, 217%, and 117%; parkinsonism: 55%, 54%, and 43%) and long-term residents (dementia: 97%, 132%, and 71%; parkinsonism: 18%, 30%, and 29%). Adjustment for pre-existing conditions did not appear to explain incidence trends, except for stroke and coronary artery disease as potential drivers of dementia incidence.

Recent immigrants across major ethnic groups in Ontario had considerably lower rates of dementia and parkinsonism than long-term residents, but this difference diminished with longer-term immigrants.

During the Randomized Assessment of Rapid Endovascular Treatment (EVT) of Ischemic Stroke (ESCAPE) trial, patient-level micro-costing data were collected. We report a cost-effectiveness analysis of EVT, using ESCAPE trial data and Markov simulation, from a universal, single-payer system using a societal perspective over a patient’s lifetime.

Primary data collection alongside the ESCAPE trial provided a 3-month trial-specific, non-model, based cost per quality-adjusted life year (QALY). A Markov model utilizing ongoing lifetime costs and life expectancy from the literature was built to simulate the cost per QALY adopting a lifetime horizon. Health states were defined using the modified Rankin Scale (mRS) scores. Uncertainty was explored using scenario analysis and probabilistic sensitivity analysis.

The 3-month trial-based analysis resulted in a cost per QALY of $201,243 of EVT compared to the best standard of care. In the model-based analysis, using a societal perspective and a lifetime horizon, EVT dominated the standard of care; EVT was both more effective and less costly than the standard of care (−$91). When the time horizon was shortened to 1 year, EVT remains cost savings compared to standard of care (∼$15,376 per QALY gained with EVT). However, if the estimate of clinical effectiveness is 4% less than that demonstrated in ESCAPE, EVT is no longer cost savings compared to standard of care.

Results support the adoption of EVT as a treatment option for acute ischemic stroke, as the increase in costs associated with caring for EVT patients was recouped within the first year of stroke, and continued to provide cost savings over a patient’s lifetime.

Clinical Trial Registration: NCT01778335

To describe the neuroimaging and other methods for assessing vascular contributions to neurodegeneration in the Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) study, a Canadian multi-center, prospective longitudinal cohort study, including reliability and feasibility in the first 200 participants.

COMPASS-ND includes persons with Alzheimer’s disease (AD; n = 150), Parkinson’s disease (PD) and Lewy body dementias (LBDs) (200), mixed dementia (200), mild cognitive impairment (MCI; 400), subcortical ischemic vascular MCI (V-MCI; 200), subjective cognitive impairment (SCI; 300), and cognitively intact elderly controls (660). Magnetic resonance imaging (MRI) was acquired according to the validated Canadian Dementia Imaging Protocol and visually reviewed by either of two experienced readers blinded to clinical characteristics. Other relevant assessments include history of vascular disease and risk factors, blood pressure, height and weight, cholesterol, glucose, and hemoglobin A1c.

Analyzable data were obtained in 197/200 of whom 18 of whom were clinically diagnosed with V-MCI or mixed dementia. The overall prevalence of infarcts was 24.9%, microbleeds was 24.6%, and high white matter hyperintensity (WMH) was 31.0%. MRI evidence of a potential vascular contribution to neurodegeneration was seen in 12.9%–40.0% of participants clinically diagnosed with another condition such as AD. Inter-rater reliability was good to excellent.

COMPASS-ND will be a useful platform to study vascular brain injury and its association with risk factors, biomarkers, and cognitive and functional decline across multiple age-related neurodegenerative diseases. Initial findings show that MRI-defined vascular brain injury is common in all cognitive syndromes and is under-recognized clinically.

Most patients with World Federation of Neurological Surgeons (WFNS) grade 5 subarachnoid hemorrhage (SAH) have poor outcomes. Accurate assessment of prognosis is important for treatment decisions and conversations with families regarding goals of care. Unjustified pessimism may lead to “self-fulfilling prophecy,” where withdrawal of life-sustaining measures (WLSM) is invariably followed by death.

We performed a cohort study involving consecutive patients with WFNS grade 5 SAH to identify variables with >= 90% and >= 95% positive predictive value (PPV) for poor outcome (1-year modified Rankin Score >= 4), as well as findings predictive of WLSM.

Of 140 patients, 38 (27%) had favorable outcomes. Predictors with >= 95% PPV for poor outcome included unconfounded 72-hour Glasgow Coma Scale motor score <= 4, absence of >= 1 pupillary light reflex (PLR) at 24 hours, and intraventricular hemorrhage (IVH) score of >= 20 (volume >= 54.6 ml). Intracerebral hemorrhage (ICH) volume >= 53 ml had PPV of 92%. Variables associated with WLSM decisions included a poor motor score (p < 0.0001) and radiographic evidence of infarction (p = 0.02).

We identified several early predictors with high PPV for poor outcome. Of these, lack of improvement in motor score during the initial 72 hours had the greatest potential for confounding from “self-fulfilling prophecy.” Absence of PLR at 24 hours, IVH score >= 20, and ICH volume >= 53 ml predicted poor outcome without a statistically significant effect on WLSM decisions. More research is needed to validate prognostic variables in grade 5 SAH, especially among patients who do not undergo WLSM.

Severe traumatic brain injury (TBI) is a major cause of morbidity and mortality in critically ill patients. Pre-hospital care and transportation time may impact their outcomes.

Using the British Columbia Trauma Registry, we included 2,860 adult (≥18 years) patients with severe TBI (abbreviated injury scale head score ≥4), who were admitted to an intensive care unit (ICU) in a centre with neurosurgical services from January 1, 2000 to March 31, 2013. We evaluated the impact of transportation time (time of injury to time of arrival at a neurosurgical trauma centre) on in-hospital mortality and discharge disposition, adjusting for age, sex, year of injury, injury severity score (ISS), revised trauma score at the scene, location of injury, socio-economic status and direct versus indirect transfer.

Patients had a median age of 43 years (interquartile range [IQR] 26–59) and 676 (23.6%) were female. They had a median ISS of 33 (IQR 26–43). Median transportation time was 80 minutes (IQR 40–315). ICU and hospital length of stay were 6 days (IQR 2–12) and 20 days (IQR 7–42), respectively. Six hundred and ninety-six (24.3%) patients died in hospital. After adjustment, there was no significant impact of transportation time on in-hospital mortality (odds ratio 0.98, 95% confidence interval 0.95–1.01). There was also no significant effect on discharge disposition.

No association was found between pre-hospital transportation time and in-hospital mortality in critically ill patients with severe TBI.

Glucose Transporter-1 (GLUT1) Deficiency Syndrome (GLUT1DS) is caused by defective transport of glucose across the blood–brain barrier into brain cells resulting in hypoglycorrhachia due to the heterozygous pathogenic variants in SLC2A1. We report on the phenotypic spectrum of patients with pediatric GLUT1DS as well as their diagnostic methods from a single center in Canada.

We reviewed patient charts for clinical features, biochemical and molecular genetic investigations, neuroimaging, treatment modalities, and outcomes of patients with GLUT1DS at our institution.

There were 13 patients. The most common initial symptom was seizures, with the most common seizure type being absence seizures (85%). Seventy-seven percent of the patients had movement disorders, and dystonia and ataxia were the most common movement disorders. Fifty-four percent of the patients did not have a history of developmental delay during their initial presentation, whereas all patients had developmental delay, intellectual disability, or cognitive dysfunction during their follow-up. All patients had a pathogenic or likely pathogenic variant in SLC2A1 and missense variants were the most common variant type.

We present 13 patients with GLUT1DS in the pediatric patient population. Atypical clinical features such as hemiplegia and hemiplegic migraine were present in an infant; there was a high prevalence of absence seizures and movement disorders in our patient population. We report an increased number of patients with GLUT1DS since the introduction of next-generation sequencing in the clinical settings. We believe that GLUT1DS should be included in the differential diagnosis of seizures, movement disorders, and hemiplegic migraine.

Childhood acute arterial ischemic stroke (AIS) is diagnosed at a median of 23 hours post-symptom onset, delaying treatment. Pediatric stroke pathways can expedite diagnosis. Our goal was to understand the similarities and differences between Canadian pediatric stroke protocols with the aim of optimizing AIS management.

We contacted neurologists at all 16 Canadian pediatric hospitals regarding AIS management. Established protocols were analyzed for similarities and differences in eight domains.

Response rate was 100%. Seven (44%) centers have an established AIS protocol and two (13%) have a protocol under development. Seven centers do not have a protocol; two redirect patients to adult neurology, five rely on a case-by-case approach for management. Analysis of the seven protocols revealed differences in: 1) IV-tPA dosage: age-dependent 0.75–0.9 mg/kg (N = 1) versus age-independent 0.9 mg/kg (N = 6), with maximum doses of 75 mg (N = 1) or 90 mg (N = 6); 2) IV-tPA lower age cut-off: 2 years (N = 5) versus 3 or 10 years (each N = 1); 3) IV-tPA exclusion criteria: PedNIHSS score <4 (N = 3), <5 (N = 1), <6 (N = 3); 4) first choice of pre-treatment neuroimaging: computed tomography (CT) (N = 3), magnetic resonance imaging (MRI) (N = 2) or either (N = 2); 5) intra-arterial tPA use (N = 3) and; 6) mechanical thrombectomy timeframe: <6 hour (N = 3), <24 hour (N = 2), unspecified (N = 2).

Although 44% of Canadian pediatric hospitals have established AIS management pathways, several differences remain among centers. Some criteria (dosage, imaging) reflect adult AIS literature. Canadian expert consensus regarding IV-tPA and endovascular treatment should be established to standardize and implement AIS protocols across Canada.

Among children with infantile spasms (ISs), those with trisomy 21 (T21) and those with normal development at onset and no identifiable etiology (previously referred to as “idiopathic”) are expected to have relatively favorable outcomes. The study objective is to determine if differences exist in treatment response, relapse, and subsequent epilepsy between these two groups when vigabatrin is used as first-line treatment.

In this retrospective study, patients were classified into the following groups and clinical features were compared: T21 (n = 24) and IS with normal development at onset and no identified etiology (n = 40; control group).

There was no significant difference in the age of IS onset, sex distribution, or treatment lag between the groups. The T21 compared to the control group required a higher mean number of anti-seizure therapies (3.6 vs. 1.9, p < 0.001), had more relapses [10 (42%) vs. 4 (10%), p < 0.005)], and had higher risk of subsequent epilepsy [11 (46%) vs. 8 (20%), p < 0.003]. Relapses were often delayed in the T21 group, with a mean of 8 months after IS cessation.

Our results differ from most studies using steroids as first-line treatment where the groups were shown to have similar treatment response and T21 patients had a low risk of relapse and subsequent epilepsy. Therefore, our results suggest that vigabatrin as first-line treatment in T21 with IS may be less favorable than steroids.