bluuebunny/crossref_metadata_2025 huggingface dataset:
P.029 Oral Daily Atogepant for the Preventive Treatment of Migraine
Increases Responder Rates for Reduction in Mean Monthly Migraine
Days
Authors: Lipton RB , Pozo-Rosich P , Blumenfeld AM , Dodick DW , McAllister P , Li Y , Lu K , Dabruzzo B , Davidovic G , Miceli R , Severt L , Finnegan M , Trugman JM
Published: January 2022

Background: The goal of the study was to assess
responder rates at various times after initiating atogepant treatment.
Methods: A 12-week phase 3 trial evaluated the
safety, efficacy, and tolerability of atogepant for preventive treatment of
migraine (ADVANCE; NCT03777059) in adult participants with a ≥1-year history
of migraine, experiencing 4-14 migraine days/month. Participants were
randomized to atogepant 10, 30, or 60mg, or placebo once daily. These
analyses evaluated ≥25%, ≥50%, ≥75%, and 100% reductions in mean monthly
migraine days (MMDs) across 12 weeks and each 4-week interval. Adverse
events (AEs) in ≥5% of participants are reported.
Results: The efficacy analysis population
included 873 participants: placebo: n=214; atogepant: 10mg: n=214; 30mg:
n=223; 60mg: n=222. Atogepant-treated participants were more likely to
experience a ≥50% reduction in the 3-month mean MMDs (56-61% vs 29% with
placebo; P<0.0001). The proportions of
participants experiencing ≥25%, ≥50%, ≥75%, and 100% reductions in mean MMDs
significantly increased during each 4-week interval (≥50% reduction: 48-71%
vs 27-47% with placebo). The most common AEs for atogepant were constipation
(6.9-7.7%) and nausea (4.4-6.1%). Conclusions:
Once-daily atogepant 10, 30, and 60mg significantly increased responder
rates at all thresholds with approximately 60% achieving a ≥50% reduction in
mean MMDs at 12 weeks.
P.038 Impact of Disease Severity on Presentation Subtype and
OnabotulinumtoxinA Utilization in Patients with Cervical Dystonia in the CD
PROBE Completer Population
Authors: Agarwal P , Barbano R , Moore H , Schwartz M , Zuzek A , Patel A
Published: January 2022

Background: The impact of cervical dystonia (CD)
severity on presentation subtype and onabotulinumtoxinA utilization was
examined in the completer population from CD PROBE (CD Patient Registry for
Observation of BOTOX® Efficacy).
Methods: In this multicenter, prospective,
observational registry, patients with CD were treated with
onabotulinumtoxinA according to injectors’ standard of care. Completers were
patients that completed all 3 treatment sessions and had accompanying data.
Results: Of N=1046 patients enrolled, n=350 were
completers. Completers were on average 57.3 years old, 74.9% female, 94.6%
white, and 60.6% toxin-naïve. Baseline severity was mild in 32.6%, moderate
in 54.3%, and severe in 13.1%. Torticollis was the most common presentation
at baseline (mild: 44.7%, moderate: 55.8%, severe: 63.0%), followed by
laterocollis (mild: 42.1%, moderate: 32.6%, severe: 26.1%). Median
onabotulinumtoxinA dose increased over time; 160U–200U for torticollis and
170U–200U for laterocollis. For all severities, median total dose increased
from injection 1 to injection 3 (mild: 138U–165U, moderate: 183U–200U,
severe: 200U–285U). Eighty-one patients (23.1%) reported 139
treatment-related adverse events. There were no treatment-related serious
adverse eventsand no new safety signals. Conclusions:
CD severity impacted presentation subtype frequency and onabotulinumtoxinA
utilization in CD PROBE, with higher and tailored dosing observed over time
and with increasing disease severity.
P.040 Prognosis in Arm and Leg Tremor Onset Parkinson Disease
Authors: Noyes E , Rajput A , Rajput A
Published: January 2022

Background: There is no biological marker of
progression in early Parkinson Disease (PD). Upper limb (UL) tremor is the
most common motor symptom at onset. The significance of lower limb (LL)
tremor remains unknown. We report on longitudinally followed
autopsy-verified PD tremor onset cases. Methods: A
chart review of longitudinally followed autopsy-verified PD cases was
performed. Age and mode of onset were recorded at initial evaluation.
Prognosis was measured by change in Hoehn and Yahr scale while on levodopa
(LD). Results: Fourty-nine patients were included.
Thirty-eight cases had upper limb (UL), four lower limb (LL), and seven
upper and lower limb (ULL) onset tremor. UL had 86.8% response to LD, LL 50%
and ULL 85.7%. Sub-analysis of UL responders found 20% mild improvement,
53.3% moderate and 26.7% marked. ULL had moderate response in 83.3% and
marked in 16.7%. LL responders only had mild improvement with LD.
Conclusions: Tremor onset is most common in UL,
followed by ULL and then LL. LL onset tremor cases have an inferior response
to LD when compared to UL and ULL cases.
P.045 Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein Antibody
Testing in Calgary: A Quality Improvement Review
Authors: Krett JD , Hou H , Alikhani K , Fritzler MJ , Burton JM
Published: January 2022

Background: Despite the availability of
cell-based assays for aquaporin-4 (AQP4) and myelin oligodendrocyte
glycoprotein (MOG) antibodies provincially, outside confirmatory testing is
often performed (typically Mayo Clinic Laboratories, USA) when results
deviate from expected. It is unknown how often this costly undertaking
(upwards of $1,200 CAN) alters diagnosis and management.
Methods: We undertook a quality improvement
project evaluating the concordance/discordance rate with select chart review
in all patients who had cell-based AQP4 or MOG IgG antibody testing at
Mitogen Diagnostics (MitogenDx; Calgary, Alberta) and subsequent testing at
Mayo Clinic Laboratories from as early as 2010 to July 2020.
Results: Preliminary review of data from January
2016 to July 2020 retrieved 145 paired tests; 10 of which were discordant
(concordance rate: 93.1%). Chart review confirmed 9 truly discordant cases,
often associated with AQP4 or MOG weak-positive results (7/9 cases) or
presumed false negative AQP4 results in prototypical neuromyelitis optica
spectrum disorder (2/9 cases). Conclusions:
Discordant results were rare when comparing MitogenDx local AQP4/MOG
antibody test results to those referred out to Mayo Clinic Laboratories,
impacting diagnosis and treatment in only 3 patients out of the total. Our
results suggest costly outside confirmatory testing of AQP4/MOG antibodies
could be reduced.
P.050 Perspectives on the use of ancillary tests for determining
neurological death: a survey of Canadian intensivists
Authors: Neves Briard J , Yu M , Carvalho LP , English SW , d’Aragon F , Lauzier F , Turgeon A , Dhanani S , McIntyre L , Shemie SD , Knoll G , Fergusson DA , Anthony SJ , Weiss MJ , Chassé M
Published: January 2022

Background: Ancillary tests are indicated to
diagnose death by neurological criteria whenever clinical neurological
examination is unreliable, but their use is variable and subject to debate.
Methods: Survey of Canadian intensivists
providing care for potential organ donors. We included closed-ended
questions and different clinical scenarios regarding the use of ancillary
tests. Results: Among 550 identified intensivists,
249 completed the survey. Respondents indicated they would be comfortable
diagnosing death based on neurological examination without ancillary tests
in the following scenarios: movement in response to stimulation (48%),
spontaneous peripheral movement (31%), inability to evaluate upper/lower
extremity responses (34%) or both oculocephalic and oculo-caloric reflexes
(17%), presence of high cervical spinal cord injury (16%) and within 24
hours of hypoxemic-ischemic brain injury (15%). Furthermore, 93% agreed that
ancillary tests should always be conducted when a complete neurological
examination is impossible, 89% if there remains possibility of residual
sedative effect and 59% in suspected isolated brainstem death.
Conclusions: Our findings suggest that Canadian
intensivists have different perceptions on what constitutes a complete and
reliable clinical neurological examination for determining death by
neurologic criteria. Some self-reported practices also diverge from national
recommendations. Further investigation and education are required to align
and standardize medical practice across physicians and systems.
P.052 Understanding the influence of APOE-ɛ4 on magnetic resonance
imaging-based hippocampal phenotypes in Alzheimer’s disease and Lewy body
dementia
Authors: Saeed U , Desmarais P , Masellis M
Published: January 2022

Background: The ɛ4-allele of apolipoprotein E
(APOE-ɛ4) increases the risk not only for
Alzheimer’s disease (AD), but also for Parkinson’s disease dementia and
dementia with Lewy bodies (collectively, Lewy body dementia [LBD]).
Hippocampal volume is an important neuroimaging biomarker for AD and LBD,
although its association with APOE-ɛ4 is
inconsistently reported. We investigated the association of
APOE-ε4 with hippocampal atrophy quantified
using magnetic resonance imaging in AD and LBD.
Methods: Electronic databases (PubMed, Embase,
PsycINFO, Scopus, Web of Science) were systematically searched for studies
published up until December 31st, 2020.
Results: Thirty-nine studies (25 cross-sectional,
14 longitudinal) were included. We observed that: (1)
APOE-ε4 was associated with greater rate of
hippocampal atrophy in AD and those who progressed from mild cognitive
impairment to AD, (2) APOE-ε4 carriers showed
greater involvement of cornu ammonis-1 hippocampal subfield versus
non-carriers in AD, (3) APOE-ɛ4 may influence
hippocampal atrophy in dementia with Lewy bodies, although longitudinal
investigations are required, and (4) APOE-ε4
associated with earlier rather than very late expression of mediotemporal
degeneration and memory-related neurocognitive impairment.
Conclusions: The role of
APOE-ɛ4 in modulating hippocampal phenotypes
may be further clarified through more homogenous, well-powered,
pathology-proven studies. Understanding the underlying mechanisms will
facilitate development of prevention strategies targeting
APOE-ɛ4.
P.055 Clinical and Electrophysiological characteristics of
anti-nodal/paranodal antibodies in chronic inflammatory demyelinating
polyradiculoneuropathy patients
Authors: Alsolaihim A , Baker S
Published: January 2022

Background: CIDP is an autoimmune polyneuropathy.
Antibodies against the Node of Ranvier have been described, NF155,NF140/186
and contactin-1. Methods: A retrospective review of
patients with CIDP who tested positive for anti-nodal/paranodal antibodies
via Western blot were evaluated. We have included 20 sero-negative CIDP
patients. All patients met definite or probable EFNS criteria. clinical,
electrophysiological data and response to treatment were obtained.
Results: Forty-five patients tested positive for
the antibodies. Sixteen were positive for NF155, 11 for NF140, 5 for
CNTN1,11 were double positive for NF155 and NF140, and 3 were triple
positive for NF155, NF140 and CNTN1.

Age of onset was similar in both seronegative (53.9 ± 3.1 yrs.) versus
seropositive (52.3 ± 2.4 yrs.).

Chronic presentation manifested in 85% of seronegative, 80% of
seropositive patients.Intrestingly,all triple-positive patients presented
with a more acute presentation (i.e,<8 wks.)

7/20 seronegative (35%),1/16 NF155, 6/11 NF140,1/5 contactin, 2/11 of
double-positive, 3/3 of triple-positive (28%,13/46) responded to IVIg.
Conclusions: No major clinical or
electrophysiological differences between groups. triple-positive patients
showed 100% response to IVIg.These results cast doubt on the specificity of
the Western blot as a clinico-electrophysiologic discriminator. Future
testing with cell-based assays will likely provide a robust measure that
will guide treatment decision.
P.059 Results From the Randomized and Open-Label Periods of the CENTAUR
Trial of Sodium Phenylbutyrate and Ursodoxicoltaurine in Amyotrophic Lateral
Sclerosis (ALS)
Authors: Paganoni S , Hendrix S , Dickson SP , Knowlton N , Cohen J , Klee J , Leslie K , Tanzi RE , Yeramian PD , Cudkowicz ME , Timmons J
Published: January 2022

Background: An oral, fixed-dose sodium
phenylbutyrate-ursodoxicoltaurine (PB-TURSO) coformulation was evaluated in
a multicenter ALS trial (CENTAUR). Methods: Adults
with definite ALS, ≤18 months from symptom onset, (N=137) were randomized
2:1 to PB-TURSO or placebo for 6 months. Completing participants were
eligible to receive PB-TURSO in the open-label extension (OLE) (≤30 months).
The primary efficacy endpoint in both periods was rate of ALS Functional
Rating Scale–Revised (ALSFRS-R) total score decline. All-cause survival was
analyzed July 2020 (longest follow-up, 35 months). Safety was assessed in
both periods. Results: Over 6-month randomized
treatment, mean ALSFRS-R total score decline was slower with PB-TURSO vs
placebo (difference, 0.42 points/month; P=0.03).
Participants receiving PB-TURSO in the OLE (continued or crossover from
placebo) maintained or initiated functional benefit beyond 6 months of
therapy. Mean hazard of death was 44% lower
(P=0.02) in the original PB-TURSO group. Overall
adverse event (AE) incidence was similar, though early (week ≤3)
gastrointestinal AEs were more frequent during initial exposure to PB-TURSO
(randomized period or OLE). Conclusions: PB-TURSO
resulted in superior retention of function in the randomized period.
Long-term OLE results support functional benefits of early vs delayed
therapy and of sustained treatment. Survival was longer in the original
PB-TURSO group after nearly 3 years.
P.060 Immunoglobulin Use For Neuromuscular Conditions: Updating British
Columbia Provincial Guidelines Through Focused Literature Review
Authors: Tse EK , Smith CB , Chapman KM , Beadon K
Published: January 2022

Background: Immune-mediated neuromuscular
conditions often cause significant disability and may require ongoing
immunomodulating therapies such as immunoglobulin (Ig). Ig use in several
neuromuscular conditions such as Chronic Inflammatory Demyelinating
Polyneuropathy (CIDP) is supported by robust evidence, however Ig is
increasingly used for other disorders. In British Columbia (BC), Ig use has
increased annually; last year, expenditure exceeded 51 million dollars, 35%
relating to neurological disease. Within the context of the pandemic, Ig
supply is at risk of shortages. Methods: A focused
literature review was conducted of CIDP, Guillain-Barré Syndrome (GBS),
Multifocal Motor Neuropathy (MMN), Myasthenia Gravis (MG), and other
neuromuscular conditions to compare BC Ig guidelines with international best
practices. Provincial recommendations for Ig use were updated accordingly.
Results: Evidence-based practices include acute
and chronic Ig use in CIDP and MMN, and acute or relapse-related treatment
in GBS and MG. Ig may be beneficial in other treatment-refractory
inflammatory disorders such as Lambert-Eaton Myasthenic Syndrome and
vasculitic neuropathy. Objective outcome measures can optimize patient care
and ensure appropriate resource utilization.
Conclusions: Updated BC guidelines emphasize
using established diagnostic criteria, objective outcome measures and
minimum effective Ig doses for neuromuscular conditions. Periodic literature
reviews on Ig use allow guidelines to remain evidence-based.
P.062 Does the intensity of brain parenchymal contrast staining on
post-recanalization dual energy head CT (DECT) of stroke patients predict
the fate of brain tissue?
Authors: Alomran B , Byrne D , Walsh J , Murray N , Settecase F , Rohr B , Rohr A
Published: January 2022

Background: On DECT, the ratio of maximum iodine
concentration within parenchyma compared to the superior sagittal sinus has
been shown to predict hemorrhagic transformation. We aimed to determine if
this ratio also predicts the development of an infarct.
Methods: 53 patients with small infarct cores
(ASPECTS≥7) and good endovascular recanalization (mTICI 2b/3) were enrolled.
Maximum brain parenchymal iodine concentration as per DECT relative to the
superior sagittal sinus (iodine ratio) was correlated with the development
of an infarct on follow up CT. Results: All patients
showed contrast staining, 52 developed infarcts in the area of staining. The
extent of infarction (smaller, equal or larger than area of staining) did
not correlate with the iodine ratio. Conclusions:
Brain parenchyma with contrast staining on post-procedure head CT almost
invariably goes on to infarct, however the extent of infarct development is
not predicted by the intensity of contrast staining.

n=53 patients with successful recanalization of anterior
circulation LVO infarct (TICI2b,3) with post procedural parenchymal
iodine staining

There was no correlation between the degree of contrast staining on
initial post procedural CT as expressed in iodine ratio and F/U infarct
extent.
P.064 Physician Approaches to Imaging and Revascularization for Acutely
Symptomatic Carotid Stenosis: Insights from the Hot Carotid Qualitative
Study
Authors: Ganesh A , Beland B , Jewett G , Campbell DJ , Varma M , Singh R , Al-Sultan A , Wong J , Menon BK
Published: January 2022

Background: Evidence informing the choice between
endarterectomy and stenting for acutely symptomatic carotid stenosis (“hot
carotid”) is dated, and uncertainties remain regarding the optimal imaging
modality. We sought to explore the thoughts of stroke physicians regarding
the perioperative management of patients with acute symptomatic carotid
stenosis. Methods: We conducted semi-structured
interviews regarding “hot carotid” management with purposive sampling of 20
stroke physicians from 14 centres in North America, Europe, Asia, and
Australia. We identified key themes using conventional qualitative content
analysis. Results: Timely imaging availability,
breadth of information gained, and surgeon/interventionalist preference
emerged as important themes informing the choice of imaging modality.
Multidisciplinary decision making, operating room/angiography suite
availability, and implications of patient age and infarct size were
important themes related to the choice of revascularization. Areas of
uncertainty included utility of carotid plaque imaging, timing of
revascularization, and the role of intervention with borderline stenosis or
intraluminal thrombus. Conclusions: Our qualitative
analysis revealed themes that were important to stroke experts. Teams
designing international trials will have to accommodate identified
variations in practice patterns and take into consideration areas of
uncertainty, such as timing of revascularization, imaging of carotid plaque
and non-stenotic features of carotid disease (intraluminal thrombus, plaque
morphology).
P.065 Physician Approaches to Anti-thrombotic Therapies for Acutely
Symptomatic Carotid Stenosis: Insights from the Hot Carotid Qualitative
Study
Authors: Beland B , Ganesh A , Jewett G , Campbell DJ , Varma M , Singh R , Al-Sultan A , Wong J , Menon BK
Published: January 2022

Background: Whereas the beneficial effect of
antiplatelet therapy for recurrent stroke prevention is well-established,
uncertainties remain regarding the optimal anti-thrombotic regimen for
acutely symptomatic carotid stenosis (“hot carotid”), particularly as
patients await revascularization. We sought to explore the approaches of
stroke physicians to peri-procedural anti-thrombotic management of patients
with “hot carotids”. Methods: We conducted
semi-structured interviews regarding “hot carotid” management with purposive
sampling of 20 stroke physicians from 14 centres in North America, Europe,
Asia, and Australia. We identified key themes using conventional qualitative
content analysis. Results: Important themes revealed
from our discussion included limitations of existing clinical trial
evidence, competing surgeon versus neurologist/internist preferences, and
single vs dual antiplatelet therapy (DAPT) while awaiting revascularization.
Areas of uncertainty included the management of stroke while on aspirin,
implications of non-stenotic features of carotid disease (intraluminal
thrombus, plaque morphology), the role of newer anti-platelet agents or
anticoagulants, platelet aggregation testing, and how soon to start DAPT.
Conclusions: Our qualitative analysis revealed
themes that were important to stakeholders in stroke care. Teams designing
international trials will have to accommodate identified variations in
anti-thrombotic practice patterns and take into consideration areas of
uncertainty, such as newer anti-thrombotic agents, and the implication of
non-stenotic features of carotid disease.
P.066 Hemispheric Reorganization of Functional Language Networks
Following Neonatal Stroke Supports Language Outcome
Authors: Emami Z , Dunkley BT , Robertson A , Westmacott R , Krishnan P , Pang EW , Dlamini N
Published: January 2022

Background: Neonatal Arterial Ischemic Stroke
(NAIS) is a common form of paediatric stroke often affecting classical
language areas. The post-stroke reorganization of functional language
networks may provide insight into later-emerging language deficits and may
help to identify at-risk children with NAIS. Methods:
A cross-sectional study of fourteen children with left (n=8; 2M; 11.1±2.2
years) or right (n=6; 3M; 12.4±4 years) middle cerebral artery (MCA) NAIS,
as well as seven neurotypical children (5M; 13.4±2.7 years), was conducted.
Children listened to correct/incorrect syntactic sentences while MEG was
recorded, and task-related functional connectivity in the time window and
frequency band of interest was determined. Language outcomes were assessed
using a battery of neuropsychological tests. Results:
A network-based analysis of syntactic language processing (4-7 Hz, 1.2-1.4s)
revealed a dysfunctional bilateral frontal-temporal network involving
language areas in patients (p=0.01). Patients
with right-MCA stroke exhibited a positive correlation between left
hemispheric connectivity and measures of language skill
(p<0.01), resembling the neurotypical
children. In left-MCA stroke patients, greater bilateral connectivity or
right laterality in the language network is correlated with good outcome
(p<0.05).
Conclusions: Depending on the hemispheric
location of stroke, certain patterns of language network reorganization may
account for impairments in a bilateral frontal-temporal language subnetwork
and support language outcome.
P.072 Ticagrelor vs Clopidogrel in Addition to Aspirin in Minor Ischemic
Stroke/ TIA – a Systematic Review & Network Meta-Analysis (NMA)
Authors: Lun R , Dhaliwal S , Zitikyte G , Roy D , Hutton B , Shorr R , Dowlatshahi D
Published: January 2022

Background: Dual antiplatelet therapy (DAPT) is
recommended after minor ischemic stroke/ transient ischemic attack (TIA),
but Clopidogrel/ Aspirin has never been compared directly to Ticagrelor/
Aspirin. Our objective is to compare these regimens in terms of efficacy and
safety. Methods: Medline, Embase, and Cochrane were
searched for randomized controlled trials (RCTs) that enrolled adults with
minor stroke/ TIA and administered antiplatelets within 72 hours. The
primary efficacy outcome is recurrent stroke or death at 90 days. We
performed a Bayesian-approach NMA. Between group comparisons were presented
as odds-ratios (OR) with 95% credible intervals (95%CI). Sucraplots were
based on calculated probabilities of rankings for individual outcomes.
Results: 9/4014 studies were included: 5 RCTs and
4 subgroup analyses. 22,098 patients were analyzed. At 90 days, both DAPT
regimens were superior to Aspirin in the prevention of recurrent stroke/
death. There was no significant difference between Clopidogrel/ ASA compared
to Ticagrelor/ ASA (OR 0.90 [95%CI 0.74 – 1.09]), although Clopidogrel/
Aspirin was ranked #1 using Sucraplots. There was no significant difference
between the interventions for mortality, bleeding, or adverse events.
Conclusions: DAPT was superior to ASA in the
prevention of recurrent strokes/ death, but there was no difference between
Clopidogrel/ ASA and Ticagrelor/ ASA.
P.082 The Toronto Concussion Study: The Feasibility and Effects of Early
Prescribed Aerobic Exercise on Recovery and Post-Concussive Symptoms in
Adults – A Pilot Study
Authors: Foster E , Kempenaar A , Chandra T , Lawrence D , Inness EL , Langer L , Danells C , Comper P , Bayley M
Published: January 2022

Background: Evidence suggests that aerobic
exercise (AE) soon after concussion may facilitate earlier recovery in
athletes. The purpose of this pilot study was to investigate the feasibility
and effects of early sub-symptom threshold AE on symptom trajectory and
recovery time in a heterogeneous adult population.
Methods: Adults presenting within 7 days of
concussion were randomized to either the experimental group: prescribed AE
(90% of symptom-limited heartrate achieved on Buffalo Concussion Treadmill
Test [BCTT]), 30 minutes/day, 5 days/week, or the control group: standard of
care exercise recommendations. Participants were assigned a heartrate
monitor bracelet to track activity. They underwent serial treadmill testing
to monitor exercise tolerance, update prescriptions and determine recovery.
Results: 20 participants (10 per arm) completed
the BCTT protocol within 7 days of injury, with 8/20 demonstrating exercise
tolerance at week 1. 66% (4/6) of those in the experimental group were
recovered by week 4, compared to only 43% (3/7) in the control group.
Average heart rate monitor compliance was 32% of the prescribed time among
all participants, and self-reported exercise prescription compliance was 43%
in the experimental group. Conclusions: Early
post-concussion aerobic exercise in the general adult population is a
promising intervention; this study will inform the design of a larger
trial.
P.083 Early and 30-day clinical and neuropsychological effects of
iatrogenic brain infarcts in the ENACT randomized-controlled trial
Authors: Ganesh A , Ospel JM , Wilson AT , Goyal M , Tymianski M , Hill MD
Published: January 2022

Background: Small brain infarcts are often seen
on diffusion-weighted MRI(DWI) following surgical/endovascular procedures.
Little is known about their clinical effects. We examined the association of
iatrogenic infarcts with outcomes in the ENACT(Evaluating Neuroprotection in
Aneurysm Coiling Therapy) trial of nerinetide in endovascular aneurysm
repair. Methods: In this post-hoc analysis, we used
multi-variable models to evaluate the association of presence/number of DWI
iatrogenic infarcts with NIHSS(National Institutes of Health Stroke Scale),
mRS(modified Rankin Scale), and cognitive/neuropsychological
scores(30-minute battery) at 1-4 and 30-days post-procedure. We also related
infarct number to a Z-score-derived composite outcome score(quantile
regression). Results: Among 185 patients(median
age:56,IQR:50-64), 124(67.0%) had iatrogenic infarcts(median:4,IQR:2-10.5).
Nerinetide resulted in fewer infarcts. Patients with infarcts had lower
Mini-Mental State Exam(MMSE) scores at 2-4 days(median:28 vs 29,
adjusted-coefficient[acoef] per additional infarct:-1.11,95%CI:-1.88 to
-0.34,p=0.005). Infarct number was associated with worse day-1 NIHSS(aOR for
NIHSS≥1:1.07,1.02-1.12,p=0.009), day 2-4 mRS(adjusted common
odds-ratio[aOR]:1.05,1.01-1.09,p=0.005) and MMSE(acoef:-0.07,-0.13 to
-0.003,p=0.040), 30-day mRS(aOR:1.04,1.01-1.07,p=0.016) and Hopkins Verbal
Learning Test scores(acoef:-0.21,-0.39 to -0.03,p=0.020), as well as worse
composite scores at 1-4 and 30-days(acoef:-0.09,-0.15 to -0.03,p=0.006).
Conclusions: Iatrogenic infarcts were associated
with subtle differences in post-procedural(1-4 days) and 30-day outcomes in
this middle-aged cohort. Future studies should use batteries of
similar/greater granularity to validate optimal measures for short- versus
long-term manifestations.
P.104 Children with Trisomy 21 and Lennox-Gastaut Syndrome with
predominant myoclonic seizures
Authors: MacDonald MJ , Crawford J , Datta A
Published: January 2022

Background: Lennox-Gastaut syndrome (LGS) is a
severe form of pediatric epilepsy that is classically defined by a triad of
drug-resistant seizures, characteristic EEG patterns, and intellectual
disability. Long-term prognosis is generally poor with progressive
intellectual deterioration and persistent seizures. At present, there are
few reported cases of LGS and Trisomy 21 (T21) in the literature. To further
delineate the spectrum of epilepsy in T21, we reviewed children with T21 and
LGS at one center over 28 years. Methods: This is a
retrospective case series. At our institution, all EEG results are entered
into a database, which was queried for patients with T21 from 1992-2019.
Pertinent electro-clinical data was obtained from medical records.
Results: 63 patients with T21 and epilepsy, 6
(10%) had LGS and were included in the study. Four of the six patients were
male and 5/6, had neuro-imaging, which was normal. Follow-up ranged from
3-20 years. Notably, 5/6 had predominant myoclonic seizures throughout the
course of their epilepsy, associated with generalized spike-wave discharges.
Conclusions: Myoclonic seizures appear to be a
predominant seizure type in patients with T21, suggestive that T21 patients
may have a unique pattern of LGS.
P.109 Diagnostic Yield of Targeted Exome Sequencing in West
Syndrome
Authors: Parfyonov M , Guella I , Evans DM , Adam S , DeGuzman C , Van Allen MI , Boelman C , Nelson TN , Farrer MJ , Connolly MB , Demos M
Published: January 2022

Background: West syndrome (WS) is characterized
by the onset of epileptic spasms usually within the first year of life.
Global developmental delay with/without regression is common. Advances in
high-throughput sequencing have supported the genetic heterogeneity of this
condition. To better understand the genetic causes of this disorder, we
investigated the results of targeted exome sequencing in 29 patients with
WS. Methods: Whole exome sequencing (WES) was
performed on an Ion ProtonTM and variant reporting was
restricted to sequences of 620 known epilepsy genes. Diagnostic yield and
treatment impact are described for 29 patients with WS.
Results: A definitely/likely diagnosis was made
in 10 patients (34%), which included 10 different genes (ALG13,
PAFAH1B1, SLC35A2, DYNC1H1, ADSL, DEPDC5, ARX, CDKL5, SCN8A,
STXBP1) known to be associated with epilepsy or WS. Most
variants were de novo dominant
(X-linked/autosomal) except for ARX (X-linked
recessive) and ADSL (autosomal recessive). 4 out
of 10 (40%) had a genetic diagnosis with potential treatment implications.
Conclusions: These results emphasize the genetic
heterogeneity of WS. The high diagnostic yield, along with the significant
genetic variability, and the potential for treatment impact, supports the
early use of this testing in patients with unexplained WS.
P.113 A Population-based Study of the Epidemiology, Healthcare Resource
Utilization and Costs of Duchenne Muscular Dystrophy in Alberta,
Canada
Authors: Chen G , Sharif B , Farris MS , Cowling T , Cabalteja C , Wu JJ , Maturi B , Klein-Panneton K , Mah JK
Published: January 2022

Background: Duchenne muscular dystrophy (DMD) is
a severe progressive neuromuscular disease. This study aimed to estimate the
prevalence, healthcare resource utilization (HRU), and medical costs of DMD
in Alberta. Methods: This retrospective study linked
provincial healthcare administrative data to identify patients with DMD
utilizing a modified diagnostic code algorithm, including males <30 years
of age. Five-year (April 2012 to March 2017) prevalence estimates were
calculated and all-cause direct HRU and costs were examined in the
first-year post-diagnosis. Results: Overall, 111
patients (median age: 12.0 years (IQR 4.7-18.3)) with DMD were identified.
The estimated five-year period prevalence was 35.72 (95% CI 31.88-39.91) per
100,000 persons. All-cause HRU in the first-year post-diagnosis included a
mean (SD) of 0.48 (1.19) hospitalizations (length of stay: 9.37 days
(36.47)), 3.96 (6.16) general practitioner visits, 28.52 (62.98) specialist
visits, and 20.14 (16.49) ambulatory care visits. Mean (SD) all-cause direct
costs were $18,868 ($29,206) CAD in the first-year post-diagnosis.
Conclusions: Patients with DMD had multiple
interactions with the healthcare system in the year following diagnosis,
resulting in substantial direct medical costs. More effective treatment
strategies are needed to improve health outcomes and reduce the burden of
DMD.
P.114 Benign tumors of peripheral nerves in children at a tertiary-care
pediatric hospital
Authors: Yaworski A , Koujok K , Cheung K , Ying Y , McMillan H
Published: January 2022

Background: Tumors affecting peripheral nerves in
children are rare. Accurate diagnosis ensures that management is appropriate
and timely. Methods: We review the clinical
presentation and utility of investigations of children with intrinsic tumors
affecting peripheral nerves at the Children’s Hospital of Eastern Ontario
(CHEO). Results: From 2009-2019, 14 cases were
identified. Mean age of symptom onset was 8.2 years (range 0.3 to 17.3
years). Presenting symptoms included painless muscle wasting (2/14), focal
muscle weakness (7/14), contracture (1/14), pain (1/14) or a painless,
palpable mass (3/14). MRI was useful at differentiating benign pediatric
nerve tumors. Peripheral nerve lipomatosis demonstrated a classic “spaghetti
string” appearance. Patients with perineurioma showed evidence of enhancing,
nodular lesions while intraneural ganglionic cysts display cystic lesion
within the nerve. Neurofibromas appear like a “bag of worms” while
schwannomas are more eccentrically positioned around the nerve. Nerve
conduction studies (NCS) or electromyography (EMG) were performed in 11/14
patients. Biopsies were performed in 9 patients and surgical management in 4
patients. Conclusions: The rare nature of peripheral
nerve tumors in children can pose diagnostic challenges. NCS/EMG are
important to assist with localization, and MRI important at distinguishing
benign tumors. Key MRI, clinical and NCS features can guide management,
potentially avoiding invasive procedures.
P.116 Cerebral Sinovenous Thrombosis in Preterm Infants
Authors: Christensen R , Krishnan P , deVeber G , Dlamini N , MacGregor D , Pulcine E , Moharir M
Published: January 2022

Background: Neonatal cerebral sinovenous
thrombosis (CSVT) can lead to severe brain injury and long-term
neurodevelopmental impairments. Previous studies of neonatal CSVT have
mainly included term infants. In this study, we examined the clinical and
radiological features, treatment and outcome of CSVT in preterm infants.
Methods: This was a retrospective cohort study of
preterm infants born <37 weeks with radiologically confirmed CSVT. All
MRI/MRV and CT/CTV scans were re-reviewed. Clinical and radiological data
were analysed using descriptive statistics, ANOVA and chi-square tests.
Results: A total of 26 preterm infants with CSVT
were included. Of these, 65% were late preterm, 27% very preterm and 8%
extreme preterm. Most were symptomatic (seizures 50%, abnormal exam 50%).
Radiological features included transverse sinus (85%) and sagittal sinus
thrombosis (42%), intraventricular hemorrhage (42%) and venous infarction
(19%). Most preterm infants with CSVT (69%) were treated with
anticoagulation. Anticoagulation was not associated with new or worsening
intracranial hemorrhage. Outcome at follow-up ranged from no impairment
(39%), mild impairment (19%), severe impairment (19%) and death (23%).
Conclusions: Preterm infants with CSVT are often
symptomatic and present with a distinct pattern of brain injury.
Anticoagulation treatment of preterm CSVT appeared to be safe. Further
studies and treatment guidelines for preterm CSVT are needed.
P.120 Case series: Clinical and genetic spectrum of SCN8A-related
disorders in British Columbia
Authors: Hebbar M , Al-Taweel N , Gill I , Boelman C , Dean RA , Goodchild SJ , Mezeyova J , Shuart NG , Johnson JP , Lee J , Michoulas A , Huh LL , Armstrong L , Connolly MB , Demos M
Published: January 2022

Background: Children with pathogenic variations
in SCN8A can present with early infantile
epileptic encephalopathy-13, benign familial infantile seizures-5 or
intellectual disability alone without epilepsy. In this case series, we
discuss six children with variants in SCN8A
managed at BC Children’s Hospital. Methods: We
describe clinical and genetic results on six individuals with
SCN8A variants identified via clinical or
research next-generation sequencing. Functional consequences of two
SCN8A variants were assessed using
electrophysiological analyses in transfected cells.
Results: Clinical findings ranged from normal
development with well-controlled epilepsy to significant developmental delay
with treatment-resistant epilepsy. Phenotypes and genotypes in our cohort
are described in the table below. Functional analysis supported
gain-of-function in P2 and loss-of-function in P4.
Conclusions: Our cohort expands the clinical and
genotypic spectrum of SCN8A-related disorders. We establish functional
evidence for two missense variants in SCN8A,
including LoF variant in a patient with intellectual disability, and autism
spectrum disorder without seizures.
P.136 Evaluating outcome prediction models in endovascular treatment for
acute ischemic stroke using baseline, treatment and post-treatment
variables
Authors: Ospel JM , Ganesh A , Kappelhof M , McDonough R , Nogueira R , McTaggart R , Menon B , Demchuk A , Poppe A , Tymianski M , Hill M , Goyal M
Published: January 2022

Background: Predicting outcomes after
endovascular treatment (EVT) for acute ischemic stroke with baseline
variables remains a challenge. We assessed the performance of stroke outcome
prediction models for EVT in acute ischemic stroke in an iterative fashion
using baseline, treatment-related and post-treatment variables.
Methods: Data from the ESCAPE-NA1 trial were used
to build 4 outcome prediction models using multi-variable logistic
regression: Model 1 included baseline variables only that are available
prior to treatment decision-making, model 2 included additional
treatment-related variables, model 3 additional early post-treatment
variables, and model 4 additional late post-treatment variables. The primary
outcome was 90-day modified Rankin Scale score 0-2. Model performance was
compared using the area under the curve (AUC).
Results: Among 1,105 patients, good outcome was
achieved by 666 (60.3%). When using baseline variables only (model 1), the
AUC was 0.74 (95%CI:0.71-0.77); this iteratively improved when treatment and
post-treatment variables were added to the models (model 2: AUC 0.77,95%CI:
0.74-0.80, model 3: AUC 0.80,95%CI:0.77-0.83, model 4: AUC 0.82,
95%CI:0.79-0.85). Conclusions: Predicting EVT
outcomes using baseline variables alone is inaccurate in one in four
patients, and may be inappropriate for patient selection. Even the most
comprehensive models with treatment-related and post-treatment factors
involve considerable uncertainty.
P.141 Does BRAF mutation status or being on systemic therapy alter the
radiological appearance of brain metastases in metastatic melanoma?
Authors: Hashmi O , Younus H
Published: January 2022

Background: The aim of this study is to
investigate the differences in the radiological appearances of brain
metastases (BM) in metastatic melanoma (MM) relative to BRAF mutation
status. As well as to compare imaging differences in BM that occur prior to
starting and during systemic therapy. Methods: A
retrospective study was done over a 5 year period. Patients with MM with BM
and known BRAF status were identified. 38 met the inclusion criteria.
Imaging features on both Computed Tomography (CT) and Magnetic Resonance
Imaging (MRI) were reviewed. Results: Irrespective of
BRAF mutation status, BM in MM tended to have a peripheral location with
30/38 cases having BM in the cerebral cortex. BRAF positive MM had a higher
frequency of irregularly enhancing BM on CT and higher occurrence of BM
showing high T1 signal on MRI. BM found during systemic treatment,
regardless of BRAF status, showed less surrounding oedema, were smaller and
harder to spot on CT. Conclusions: Understanding
imaging features based on genetics could inform future management. The
subtle features of BM on CT during systemic therapy means careful follow up
with MRI may be indicated to confirm the diagnosis and to more accurately
assess the burden of brain disease.
P.142 Safety and Efficacy of Vascular Closure Devices in Interventional
Radiological Procedures
Authors: Kim E , Sebastio-Goncalves B , Lee A , Sudarshan S , Shankar J
Published: January 2022

Background: Vascular closure devices (VCDs) are
routinely used in both neurovascular and vascular interventional procedures.
The purpose of our study was to assess the safety and efficacy of the VCDs
for diagnostic and therapeutic neurovascular and vascular procedures.
Methods: The study was approved by the University
of Manitoba research ethics board. A retrospective review was conducted of
the database between January 2017 and December 2019. The data was collected
from the Picture Archiving and Communication System (PACS) and collected in
an excel spreadsheet. Patient demographics and clinical information was
collected. Descriptive statistics and chi-squared tests were performed using
STATA 13 software. A p<0.05 was considered significant.
Results: VCD was used in a total of 2072
patients. VCDs were successfully deployed in 94% with 6% failure. Immediate
perioperative complications were seen in 6.2% patients. The complication
rates were significantly (p=0.025) associated with the type of procedure.
Complications were seen significantly (p=0.044) higher in outpatients
compared to inpatients and those from emergency room.
Conclusions: VCDs were successfully deployed in
96VCDs were successfully deployed in 94% of the patient with 6%
perioperative complications. Most of the complications were minor and
complications were more commonly associated with outpatients procedures and
with diagnostic vascular procedures.
P.145 Perceived Limits of Endovascular Treatment for Secondary Medium
Vessel Occlusion Stroke
Authors: McDonough RV , Cimflova P , Kappelhof M , Singh N , Kashani N , Ospel JM , Demchuk A , Menon B , Chen M , Sakai N , Fiehler J , Goyal M
Published: January 2022

Background: Thrombus embolization during
endovascular treatment (EVT) occurs in up to 9% of cases, making secondary
medium-vessel occlusions (MeVOs) of particular interest to
neurointerventionalists. We sought to gain insight into the current EVT
approaches for secondary MeVO stroke in an international case-based survey
as there are currently no clear recommendations for EVT in these patients.
Methods: Participants were presented with three
secondary MeVO cases, each consisting of three case-vignettes with changes
in patient neurological status (improvement, no change, unable to assess).
Clustered multivariable logistic regression analyses were used to assess
factors influencing the decision to treat. Results:
366 physicians from 44 countries took part. The majority (54.1%) were in
favor of EVT. Participants were more likely to treat occlusions in the
anterior M2/3 (74.3%; risk ratio [RR]2.62, 95%CI:2.27-3.03) or A3 (59.7%;
RR2.11, 95%CI:1.83-2.42) segment, compared to the M3/4 segment
(28.3%;reference). Physicians were less likely to pursue EVT in patients
with neurological improvement (49.9% versus 57.0%; RR0.88, 95%CI:0.83-0.92).
Interventionalists and more experienced physicians were more likely to treat
secondary MeVOs. Conclusions: Physician’s willingness
to treat secondary MeVOs endovascularly is limited and varies per occlusion
location and change in neurological status. More evidence on the safety and
efficacy of EVT for secondary MeVO stroke is needed.
P.151 Repeat surgery for recurrent trigeminal neuralgia: a systematic
review and meta-analysis
Authors: Rheaume AR , Ostertag C , Pietrosanu M , Sankar T
Published: January 2022

Background: The success of repeat surgery for
recurrent trigeminal neuralgia (TN)—with microvascular decompression (MVD),
percutaneous rhizotomy (PR), or stereotactic radiosurgery (SRS)—is not
well-studied. We performed a systematic review and meta-analysis of the
literature on repeat surgery recurrent TN, focusing on the durability of
pain relief and relative efficacy of MVD, PR, and SRS.
Methods: A PRISMA systematic review of
Medline/Embase/Pubmed identified studies of adults with unilateral
idiopathic TN undergoing repeat surgery. The primary outcome of complete
pain relief (CPR) at last follow-up was analyzed with a multivariate
mixed-effects meta-analysis of proportions. Results:
Seventy-eight studies met criteria; 61 were included in meta-analyses,
containing 29/14/25 cohorts with 900/684/1353 patients undergoing MVD/PR/SRS
respectively (mean age 64.7 years, 41% males). Initial CPR was 69%
(74%/85%/52%). CPR at mean 39.7 month follow-up (38.3/38.8/41.0) was 48%
(59%/60%/34%). Initial CPR for both MVD (CPR: 0.78 [0.70-0.85]) and PR (CPR:
0.93 [0.83-0.98]) was superior to SRS (CPR: 0.48 [0.35-0.61]). At follow-up,
MVD (0.45 [0.32-0.58]) and PR (0.45 [0.30-0.60]) trended towards superior
CPR versus SRS (0.25 [0.15-0.37]). Conclusions: Half
of recurrent TN patients achieve good pain control 3 years after repeat
surgery. MVD/PR showed superior initial pain relief and likely better
long-term relief. These findings can inform surgical decision-making in this
challenging population.
P.160 Impact of peritumoral edema during tumor treatment field therapy: a
computational modelling study
Authors: Lang S , Gan L , McLennan C , Monchi O , Kelly J
Published: January 2022

Background: Tumor treatment fields (TTFields) are
an approved adjuvant therapy for glioblastoma. The magnitude of applied
electrical field is related to the anti-tumoral response. However,
peritumoral edema (ptE) may result in shunting of electrical current around
the tumor, thereby reducing the intra-tumoral electric field. In this study,
we address this issue with computational simulations.
Methods: Finite element models were created with
varying amounts of ptE surrounding a virtual tumor. The electric field
distribution was simulated using the standard TTFields electrode montage.
Electric field magnitude was extracted from the tumor and related to edema
thickness. Two patient specific models were created to confirm these
results. Results: The inclusion of ptE decreased the
magnitude of the electric field within the tumor. In the model considering a
frontal tumor and an anterior-posterior electrode configuration, ≥ 6 mm of
ptE decreased the electric field by 52%. In the patient specific models, ptE
decreased the electric field within the tumor by an average of 26%. The
effect of ptE on the electric field distribution was spatially heterogenous.
Conclusions: Given the importance of electric
field magnitude for the anti-tumoral effects of TTFields, the presence of
edema should be considered both in future modelling studies and as a
predictor of non-response.
P.164 The Rising Incidence and Prevalence of Brain Tumours: a Canadian
epidemiological study
Authors: Voisin MR , Sasikumar S , Mansouri A , Zadeh G
Published: January 2022

Background: Primary malignant brain tumours
account for over one third of all brain tumours and are associated with high
morbidity and mortality. The purpose of this paper is to estimate the rate
and trends of incidence and prevalence for primary malignant CNS tumours in
Canada from 1992 to 2017. Methods: An epidemiological
study using publicly available data from Statistics Canada: Canadian Cancer
Registry (CCR) from 1992 to 2017 for all of Canada was conducted. Incidence
and prevalence per 100,000, age-standardized incidence, and age-standardized
prevalence per 100,000 person-years of primary malignant CNS tumours were
calculated and stratified by sex and age: pediatric (0-19), adult (20-64),
and elderly (>64) populations. Results: During the
study period, incidence and prevalence increased by 27.3% and 28.8%,
respectively. Males accounted for 56% of all diagnoses and experienced
decreased survival compared to females one year after diagnosis (p-value =
0.04). Age-standardized rates of incidence and prevalence were highest in
elderly populations. Conclusions: Overall, the
incidence of primary malignant CNS tumours has increased from 1992 to 2017
with males and the elderly disproportionately affected. Increased healthcare
resources and awareness are needed to better identify and deliver
evidence-based care for these patients.