Cerebral radionecrosis, a subacute or late effect of radiotherapy, can be debilitating and difficult to treat. Steroids can reduce symptoms, but have significant long-term side effects. Bevacizumab has been shown to reduce edema and other radiologic features associated with radionecrosis and improve patient symptoms. We report our experience using bevacizumab for cerebral radionecrosis.

We retrospectively reviewed the charts of all patients treated at our institution with bevacizumab for non-glioma-associated cerebral radionecrosis. We recorded change in symptoms, change in steroids, change in performance status, time to tumor progression, and time to death. We delineated the volume of necrosis pre- and post-bevacizumab on T1-post-gadolinium and fluid-attenuated inversion recovery (FLAIR) MRI scans.

We identified 15 patients, 8 with brain metastases, 6 with meningioma, and 1 with nasopharyngeal carcinoma. Most received four doses of bevacizumab, 7.5 mg/kg q 3 weeks × 4 doses. Neuroimaging demonstrated a reduced T1 gadolinium-enhancing volume and edema in 14/15 patients (the average reduction in T1-post-gadolinium volume was 3.0 cm3, and average reduction in FLAIR volume was 27.9 cm3). There was no appreciable change in patient performance status. Steroid doses decreased in five of nine patients. There was a high rate (26%) of adverse events, including pulmonary embolism, stroke, and wound dehiscence. The median progression-free survival was 6.5 months.

Although bevacizumab is commonly prescribed for cerebral radionecrosis, in our retrospective cohort, the clinical benefits were modest and there was significant toxicity.

Strategies to modulate the tumor microenvironment (TME) have opened new therapeutic avenues with dramatic yet heterogeneous intertumoral efficacy in multiple cancers, including glioblastomas (GBMs). Therefore, investigating molecular actors of TME may help understand the interactions between tumor cells and TME. Immune checkpoint proteins such as a Cluster of Differentiation 80 (CD80) and CD86 are expressed on the surface of tumor cells and infiltrative tumor lymphocytes. However, their expression and prognostic value in GBM microenvironment are still unclear.

In this study, we investigated, in a retrospective local discovery cohort and a validation TCGA dataset, expression of CD80 and CD86 at mRNA level and their prognostic significance in response to standard of care. Furthermore, CD80 and CD86 at the protein level were investigated in the discovery cohort.

Both CD80 and CD86 are expressed heterogeneously in the TME at mRNA and protein levels. In a univariate analysis, the mRNA expression of CD80 and CD86 was not significantly correlated with OS in both local OncoNeuroTek dataset and TCGA datasets. CD80 and CD86 mRNA high expression was significantly associated with shorter progression free survival (PFS) (p < 0.05). These findings were validated using the TCGA cohort; higher CD80 and CD86 expressions were correlated with shorter PFS (p < 0.05). In multivariate analysis, CD86 mRNA expression was an independent prognostic factor for PFS in the TCGA dataset only (p < 0.05).

CD86 could be used as a potential biomarker for the prognosis of GBM patients treated with immunotherapy; however, additional studies are needed to validate these findings.

To identify sources of distress experienced by trainees when providing neuropalliative care and to explore the perceived and unperceived educational needs of trainees learning to deliver neuropalliative care.

This study is a post hoc analysis of a qualitative investigation performed at a single Canadian academic center with active clinical services in palliative medicine, neurology, and neurosurgery. Grounded theory methodology was used to explore trainees’ perspectives when learning neuropalliative care. This study used focus groups, using open-ended questions, to elicit participants’ experiences providing neuropalliative care as well as to explore the challenges in neuropalliative care.

Qualitative analysis identified multiple sources of distress for trainees in neuropalliative care and broad themes emerged: 1) a lack of experience and knowledge, 2) the emotional toll of learning neuropalliative care, and 3) prognostic uncertainty in neuropalliative care.

Our results suggest that palliative neurology curricula should focus not only on symptom management but also on strategies for improving communication about prognosis and managing clinical uncertainty. Improving trainee comfort and confidence in neuropalliative care throughout the illness trajectory may alleviate sources of distress during training and increase quality of care.

Cervico-cephalic arterial dissections (CeAD) are an important cause of stroke in young patients. This study aimed to determine the frequency and predictors of recanalization in spontaneous CeAD and to study the effect of recanalization on functional outcomes.

We identified patients presenting with acute ischemic stroke secondary to CeAD from the CT angiography (CTA) database of the Calgary Stroke Program. Dissections were diagnosed based on standard clinical and imaging findings. At the discretion of treating stroke Neurologists, the patients were either treated with single antiplatelet or dual antiplatelet or triple therapy. Follow-up imaging with CTA, magnetic resonance imaging, and DSA was completed, and a Modified Rankin scale (mRS) was performed to determine the outcome.

Fifty-six patients with CeAdD were studied. Thirty-four patients (18 VAD; vertebral artery dissection and 16 CAD; carotid artery dissection) were followed up for recanalization. Complete recanalization was observed in 27 subjects; 13 patients with VAD recanalized in comparison to 14 with CAD (p = 0.40). All non-recanalized patients had hypertension. A good clinical outcome (mRS ≤ 2) was observed in 47 patients. Interestingly, the likelihood of a good neurological outcome was not influenced by recanalization status. There was no difference in clinical outcome for different sites in VAD, whereas patients with intracranial CAD had severe strokes (NIHSS > 21).

CeAD has good recanalization rates and neurological outcomes, with recanalization seen even in vessels with initial complete occlusion. The presence of hypertension may influence recanalization. The efficacy of dual antiplatelets and heparin for early recanalization needs to be assessed in future clinical trials.

We investigated the change in limbic structure volumes and intrinsic limbic network in patients with obstructive sleep apnea (OSA) compared to healthy controls.

We enrolled 26 patients with OSA and 30 healthy controls. They underwent three-dimensional T1-weighted magnetic resonance imaging (MRI) on a 3 T MRI scanner. The limbic structures were analyzed volumetrically using the FreeSurfer program. We examined the intrinsic limbic network using the Brain Analysis with Graph Theory program and compared the groups' limbic structure volumes and intrinsic limbic network.

There were significant differences in specific limbic structure volumes between the groups. The volumes in the right amygdala, right hippocampus, right hypothalamus, right nucleus accumbens, left amygdala, left basal forebrain, left hippocampus, left hypothalamus, and left nucleus accumbens in patients with OSA were lower than those in healthy controls (right amygdala, 0.102 vs. 0.113%, p = 0.004; right hippocampus, 0.253 vs. 0.281%, p = 0.002; right hypothalamus, 0.028 vs. 0.032%, p = 0.002; right nucleus accumbens, 0.021 vs. 0.024%, p = 0.019; left amygdala, 0.089 vs. 0.098%, p = 0.007; left basal forebrain, 0.020 vs. 0.022%, p = 0.027; left hippocampus, 0.245 vs. 0.265%, p = 0.021; left hypothalamus, 0.028 vs. 0.031%, p = 0.016; left nucleus accumbens, 0.023 vs. 0.027%, p = 0.002). However, there were no significant differences in network measures between the groups.

We demonstrate that the volumes of several limbic structures in patients with OSA are significantly lower than those in healthy controls. However, there are no alterations to the intrinsic limbic network. These findings suggest that OSA is one of the risk factors for cognitive impairments.

Sensory-motor decoupling at the cortical level involving cholinergic circuitry has also been reported in Parkinson’s Disease (PD). Short-latency afferent inhibition (SAI) is a transcranial magnetic stimulation (TMS) paradigm that has been used previously to probe cortical cholinergic circuits in well-characterised subgroups of patients with PD. In the current study, we compared SAI in a cohort of PD patients at various stages of disease and explored correlations between SAI and various clinical measures of disease severity.

The modified Hoehn and Yahr (H&Y) scale was used to stage disease in 22 patients with PD. Motor and cognitive function were assessed using the MDS-UPDRS (Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale) part III and MoCA (Montreal Cognitive Assessment) score, respectively. Objective gait assessment was performed using an electronic walkway (GAITRite®). SAI was measured as the average percentage inhibition of test motor-evoked potentials (MEPs) conditioned by electrical stimulation of the contralateral median nerve at the wrist.

SAI was significantly reduced in patients with advanced PD (H&Y stage 3) compared to early PD patients (H&Y stage 1) on pairwise comparison. The visuospatial executive function and orientation domains of cognition demonstrated significant negative associations with SAI.

Cortical sensory-motor integration is progressively diminished as disease progresses. The observation that a reduction in SAI is associated with a reduction in cognitive function possibly reflects the progressive involvement of cortical cholinergic circuits in PD with increasing motor stage. Future longitudinal studies are necessary to confirm this preliminary result.

Neuronal intranuclear inclusion disease (NIID) is a rare slowly progressive neurodegenerative disorder that is characterized pathologically by the presence of eosinophilic intranuclear inclusions. NIID is a heterogeneous disease with diverse clinical manifestations, making diagnosis difficult. Here, we analyzed the clinical, pathological, and radiological features of Chinese NIID patients to improve our understanding of NIID.

A total of 17 patients with sporadic NIID were recruited from the Ruijin Hospital Database between 2014 and 2021. Clinical patient information and brain MRI data were collected. All of the patients underwent standard skin biopsy procedures.

The average age of onset for symptoms was 60.18 years, and the average duration of illness was 4.06 years. All patients were diagnosed with NIID due to the presence of intranuclear inclusions confirmed by skin biopsy. Tremor was the most common initial symptom. The average ages at onset and at diagnosis were both lower in patients with tremor than in patients without tremor. NIID may be a systemic disease that affects multiple organs, for one patient had a history of chronic renal insufficiency for more than 10 years. In addition to high-intensity U-fibers signals on diffusion-weighted imaging, there were several other MRI findings, such as focal leukoencephalopathy and cortical swelling. Encephalitic episodes followed by reversible leukoencephalopathy was another important imaging feature of NIID.

The clinical manifestations of NIID are highly variable. Tremor may be the most common initial symptom in certain cohorts. Encephalitic episodes followed by reversible asymmetric leukoencephalopathy may also indicate this disease.

The Passive Surveillance Stroke Severity (PaSSV) Indicator was derived to estimate stroke severity from variables in administrative datasets but has not been externally validated.

We used linked administrative datasets to identify patients with first hospitalization for acute stroke between 2007-2018 in Alberta, Canada. We used the PaSSV indicator to estimate stroke severity. We used Cox proportional hazard models and evaluated the change in hazard ratios and model discrimination for 30-day and 1-year case fatality with and without PaSSV. Similar comparisons were made for 90-day home time thresholds using logistic regression. We also linked with a clinical registry to obtain National Institutes of Health Stroke Scale (NIHSS) and compared estimates from models without stroke severity, with PaSSV, and with NIHSS.

There were 28,672 patients with acute stroke in the full sample. In comparison to no stroke severity, addition of PaSSV to the 30-day case fatality models resulted in improvement in model discrimination (C-statistic 0.72 [95%CI 0.71–0.73] to 0.80 [0.79–0.80]). After adjustment for PaSSV, admission to a comprehensive stroke center was associated with lower 30-day case fatality (adjusted hazard ratio changed from 1.03 [0.96–1.10] to 0.72 [0.67–0.77]). In the registry sample (N = 1328), model discrimination for 30-day case fatality improved with the inclusion of stroke severity. Results were similar for 1-year case fatality and home time outcomes.

Addition of PaSSV improved model discrimination for case fatality and home time outcomes. The validity of PASSV in two Canadian provinces suggests that it is a useful tool for baseline risk adjustment in acute stroke.

Leber hereditary optic neuropathy (LHON) is a rare but bilaterally blinding disease. Three characteristic disease-causing point mutations, and other less common mutations, are most often found on the mitochondrially encoded genes of NADH-ubiquinone oxidoreductase core subunits (MT-ND). The purpose of this study is to provide an overview of LHON mutations in Southwestern Ontario and to describe the associated demographic and clinical characteristics.

A retrospective genetic and clinical chart review was performed from January 2015 to 2020. Patients were identified within a mitochondrial mutation database and included if a mutation was detected on the MT-ND1, -ND4, or -ND6 genes. A clinical chart review was done on all available patients.

Forty-five of 63 patients identified had classic disease-causing mutations (6.7% m.3460G>A, 44.4% m.11778G>A, and 48.9% m.14484T>C). Several of the remaining 18 patients had rare mutations previously documented in association with LHON. Of the 14 patients with clinical charts accessible for review, 12 had symptomatic disease, and all but one had bilateral optic neuropathies. Nine patients had classic LHON mutations and 3 had possible novel mutations; 7 were males; 9 had final visual acuity ≤ 20/200 in at least one eye; and 6 of those had ≤20/400 in both eyes.

This study adds to the literature on LHON in Canada, and specifically Southwestern Ontario. The demographic and clinical data regarding LHON in this geographic location, as well as possible novel disease-causing mutations, provide important information to aid clinicians in recognizing cases of LHON that may otherwise be disregarded.

The objective of this study is to determine the physical evaluations and assessment tools used by a group of Canadian healthcare professionals treating adults with spasticity.

A cross-sectional web-based 19-question survey was developed to determine the types of physical evaluations, tone-related impairment measurements, and assessment tools used in the management of adults with spasticity. The survey was distributed to healthcare professionals from the Canadian Advances in Neuro-Orthopedics for Spasticity Congress database.

Eighty study participants (61 physiatrists and 19 other healthcare professionals) completed the survey and were included. Nearly half (46.3%, 37/80) of the participants reported having an inter- or trans-disciplinary team managing individuals with spasticity. Visual observation of movement, available range of motion determination, tone during velocity-dependent passive range of motion looking for a spastic catch, spasticity, and clonus, and evaluation of gait were the most frequently used physical evaluations. The most frequently used spasticity tools were the Modified Ashworth Scale, goniometer, and Goal Attainment Scale. Results were similar in brain- and spinal cord-predominant etiologies. To evaluate goals, qualitative description was used most (37.5%).

Our findings provide a better understanding of the spasticity management landscape in Canada with respect to staffing, physical evaluations, and outcome measurements used in clinical practice. For all etiologies of spasticity, visual observation of patient movement, Modified Ashworth Scale, and qualitative goal outcomes descriptions were most commonly used to guide treatment and optimize outcomes. Understanding the current practice of spasticity assessment will help provide guidance for clinical evaluation and management of spasticity.

Coronavirus disease 2019 (COVID-19) infection causes a wide variety of neurological disorders by affecting both central and peripheral nervous systems. The cytokine storm (CS) has been blamed for the development of severe neurological disorders in COVID-19. However, the relationship between COVID-19 CS and neurological manifestations has not been adequately studied. Thus, we aimed to investigate the neurological presentations in patients with COVID-19 CS.

The study population consisted of hospitalized moderate-to-severe COVID-19 patients. It was divided into two groups CS (36 patients, 29.3%) and non-CS (87 patients, 70.7%) based on significant clinical symptoms, elevated inflammatory marker levels, radiological findings, and interleukin-6 levels (IL-6).

The three most common neurological symptoms in the CS group were altered level of consciousness, headache, and unsteadiness. Altered level of consciousness was higher in the CS group (69.4%) than the non-CS group (25.3%) (p:0.001). The frequency of headache was comparable in both groups (p:0.186). The number of patients requiring intensive care unit and intubation was higher in the CS group (p:0.005 and p:0.001). The mortality rate in the CS group (38.9%) was higher than the non-CS group (8.0%) (p:0.001). IL-6, CRP, ferritin, neutrophil-lymphocyte ratio, procalcitonin, and D-dimer levels were higher in the CS group (for all p:0.001) while lymphocyte count was lower (p:0.003).

The most common neurological presentation in patients with CS was altered level of consciousness. The presence of CS was an independent risk factor for high mortality.

The body of evidence regarding self-management programs (SMPs) for adult chronic non-cancer pain (CNCP) is steadily growing, and regular updates are needed for effective decision-making.

To systematically identify, critically appraise, and summarize the findings from randomized controlled trials (RCTs) of SMPs for CNCP.

We searched relevant databases from 2009 to August 2021 and included English-language RCT publications of SMPs compared with usual care for CNCP among adults (18+ years old). The primary outcome was health-related quality of life (HR-QoL). We conducted meta-analysis using an inverse variance, random-effects model and calculated the standardized mean difference (SMD) and associated 95% confidence interval (CI) and statistical heterogeneity using the I 2 statistic.

From 8538 citations, we included 28 RCTs with varying patient populations, standards for SMPs, and usual care. No RCTs were classified as having a low risk of bias. There was no evidence of a significant improvement in overall HR-QoL, irrespective of pain type, immediately post-intervention (SMD 0.01, 95%CI −0.21 to 0.24; I 2 57%; 11 RCTs; 979 participants), 1–4 months post-intervention (SMD 0.02, 95%CI −0.16 to 0.20; I 2 48.7%; 12 RCTs; 1160 participants), and 6–12 months post-intervention (SMD 0.07, 95%CI −0.06 to 0.21; I 2 26.1%; 9 RCTs; 1404 participants). Similar findings were made for physical and mental HR-QoL, and for specific QoL assessment scales (e.g., SF-36).

There is a lack of evidence that SMPs are efficacious for CNCP compared with usual care. Standardization of SMPs for CNCP and better planned/conducted RCTs are needed to confirm these conclusions.

Community stroke rehabilitation teams (CSRT) provide an individualized home-based rehabilitation service to patients recovering from stroke.

To examine whether there is an improvement in the social participation of patients who received a rehabilitation program provided by CSRT. The secondary objectives were to show if there is an improvement in the patients’ quality of life and a reduction in the caregiver burden.

Retrospective cohort study, pragmatic in real-care conditions. The rehabilitation program delivered by the CSRT was adapted to the needs of the patients and caregivers. The outcome questionnaires included: the Frenchay Activity Index (FAI), the Minizarit, the EuroQol EQ5D, and the Barthel Index. The primary outcome measure was the FAI.

We included 206 patients followed by the CSRT over the 2018–2020 study period, for whom the primary endpoint was present. The mean age was 66.3 ± 12.7 years, the post-stroke delay was 16.4 ± 32.7 months, and the Barthel index was 66.42 ± 12.6. The duration of the rehabilitation program was on average 162 ± 109 days. We observed a significant improvement in the FAI, from 12.9 ± 10.4 to 17.85 ± 12.4 (p < 0.00001); in the EuroQol, from 57.51 ± 19.96 to 66.36 ± 18.87 (p < 0.00001); in the mini-Zarit, from 2.49 ± 1.75 to 2.06 ± 1.67 (p = 0.0002); and in the Barthel index, from 66.42 ± 12.67 to 84.81 ± 23.70 (p < 0.001).

Patients who received a rehabilitation program by the CSRT have an improvement in their social participation, and their informal caregivers have a reduction in their burden.

Amyotrophic lateral sclerosis (ALS) is a degenerative disease of the nervous system that primarily affects motor neurons. ALS type 8 (ALS8) is a familiar form with predominant involvement of lower motor neurons, tremor, and slow progression.

The aim of this study was to describe sensory involvement in a cohort of ALS8 patients and compare it with the characteristics of sporadic ALS (sALS) patients and controls.

We compared data from 40 ALS8 and 10 sALS patients assessed by neurological evaluation and electrophysiological study. Skin biopsies were performed in these patients and 12 controls for analysis of intraepidermal nerve fiber (IENF) density by protein gene product 9.5 (PGP 9.5) immunohistochemistry.

The ALS8 group was younger than the sALS group at the onset of symptoms (p < 0.05) and had a longer disease evolution (p < 0.01). Sensory abnormalities were evident in 35% of the ALS8 and 30% of the sALS patients by neurological examination, and all ALS patients presented normal sensory nerve action potentials. Despite being similar in the ALS8 and sALS groups, IENF density in the ALS8 group was lower than that in the controls (p < 0.0005). In the ALS8 group, IENF density was significantly lower in patients with impairment of vibratory sensation than in those without this finding (p < 0.05) and in females than in males (p < 0.05).

Sensory impairment and decreased IENF density are present in ALS8 patients at a frequency and intensity similar to that in the sALS group.

We aimed to evaluate the perceived effectiveness of interventions implemented by Canadian neurology residency programs for the 2020–2021 iteration of the Canadian Resident Matching Service (CaRMS).

A cross-sectional survey was distributed to Canadian neurology residency programs and final-year Canadian medical students who applied to at least one neurology program during the 2020–2021 match cycle. The surveys evaluated pre-interview and interview period interventions implemented by Canadian neurology residency programs and accessed by medical students.

Thirty-five medical students and 13 out of 15 institutions in Canada with neurology residency programs responded to the survey. Multiple adaptations were implemented, including social media advertisement, web-based platforms, pre-interview information sessions, and teaching sessions, with all surveyed programs implementing at least two virtual interventions. We found that all interventions were perceived as adequate by a majority (>60%) of medical students, with pre-interview period virtual information sessions perceived as effective by the largest proportion of respondents. All Canadian neurology residency programs held virtual interviews for the 2020–2021 cycle, and most programs utilized the same interview structure as prior years. There was discordance between residency program stakeholders and medical students on the most helpful interview period modality. Medical students found the hospital tours and information sessions most valuable, whereas program stakeholders perceived the virtual socials and interviews as most helpful.

The COVID-19 pandemic has led to innovative adaptations implemented by Canadian neurology residency programs, which were seen as effective by both medical students and program stakeholders.

Half of Guillain–Barré syndrome (GBS) present elevated cerebrospinal fluid (CSF) protein levels within 1 week since symptom onset and 80% within 2 weeks. Our objective was to determine the clinical and prognostic implication of albuminocytological dissociation in early GBS.

An ambispective cohort study was conducted. Good outcome was considered if the patient was able to walk unaided (Guillain-Barré disability score [GDS] ≤ 2 points) at 3-month follow-up. Patients were classified into two groups: with and without albuminocytological dissociation; we compared clinical and paraclinic characteristics between the groups. We analyzed clinical and electrophysiological factors related to presenting early dissociation through a multivariate model.

We included 240 patients who fulfilled Asbury criteria for GBS. On further selection, only 94 patients fulfilled inclusion. Mean age was 45.94 ± 17.1 years and 67% were male. Median time from symptom onset to admission was 5 days (IQR 3–6). Regarding albuminocytological dissociation and electrophysiological variants, we found a significant difference: acute inflammatory demyelinating polyneuropathy (AIDP) [60.6% vs 26.2%, p = 0.002], acute motor axonal neuropathy (AMAN) [21.2% vs 49.1%, p = 0.009] and acute motor sensory axonal neuropathy (AMSAN) [12.1% vs 1.6%, p = 0.05]. We did not observe significant differences in recovery of independent walking in short term between both groups. The presence of conduction block in any variant (OR 3.21, 95% CI 1.12–9.16, p = 0.02) and absence of sural registration (OR 5.69, 95% CI 1.48–21.83, p = 0.011) were independent factors related to early dissociation.

Early dissociation (<7 days) is not associated with any particular clinical feature or unfavorable outcome. It is more common to see in AIDP rather than axonal variants.