Rationale: To address this knowledge gap by examining the relationship between impulsivity and planning/decision-making in OCD using the Tower of London (TOL) task using EEG.
Aim/Objective: This study aims to investigate the impact of impulsivity on planning and decision-making in OCD using EEG and the TOL task.
Hypothesis: Individuals with OCD will exhibit distinct patterns of latency and spectral power during the TOL task compared to controls, reflecting increased impulsivity and cognitive effort during decision-making.

• The groups could be matched for age & handedness.
• The OCD group scored significantly higher than the control group in domains of attention, planning & total scores in the BIS-11 scale indicative of relatively poor sustained attention and impulsive planning in the OCD group than HCs.
• In the left frontal, the latency for the least complex task (3 moves) was significantly higher in the control group.
• There were no significant differences in amplitude or latencies for more complex tasks.

 

• Evaluation of neurological symptoms in a child differs from adults; for example, the presentation of carpal tunnel syndrome in children warrants careful considerations of secondary underlying etiologies
• We present a case of a five-year-old female with bilateral hand motor and sensory symptoms with accompanying skeletal and ocular abnormalities
• This case illustrates the importance of systemic evaluation in neurologic presentations. Understanding the underlying cause of otherwise common presentations is paramount to guide management and counseling.   

• A five-year-old female presented with a three-year history of progressive difficulty with fine motor tasks involving the bilateral index and thumb, such as holding a pencil or cutlery and managing zippers or buttons
• other symptoms include: difficulty flexing the PIP and DIP joints of all fingers (excluding the thumb) on the right and index and long fingers on the left, lack of pain sensation when removing splinters lodged in the thumb and index fingers, use of ring finger to sense the temperature of items, stiffness in both her wrist and ankle joints  
• Otherwise a normal developing child
• Physical exam: height averaged in the 10-20^th percentile and her weight averaged in the 40-50^th percentile, normal facial features and range of motion in wrists and ankles, dactylitis, bilateral thenar wasting, bilateral restriction of flexor tendon movement at the level of A1 and A2 pulleys with components of pulley and tendon thickening leading to both incomplete finger flexion and extension deficits at the level of distal interphalangeal joints in her index and long fingers, bilateral weakness of the abductor pollicus brevis (MRC 2-3/5) and decreased sensation to light touch in the thumb, index, and long fingers
• see Table 1 for investigations
• patient underwent bilateral carpal tunnel release and neurolysis of the median nerves. In the same operation, she also had bilateral index and long finger pulley release and tenosynovectomy (Figure 1)
• However, she continued to have neurological symptoms and a repeat procedure was done 2 years later.  After her second operation, she continues to have neurological symptoms.

• Carpal tunnel syndrome (CTS) is less common in children compared to adults but can be associated with significant morbidity
• In adults, most common causes are mechanical trauma and ischemic damage to the nerve, in children this is more likely to be associated with a secondary condition such as metabolic storage diseases (i.e. mucopolysaccharidoses (MPS)), familial syndromes (i.e. familial carpal tunnel syndrome), genetic syndromes (i.e. Weill–Marchesani Syndrome (WMS), Hereditary neuropathy with liability to pressure palsies, other causative genes include COMP, BGN, ACAN, COL5A1, and IL6R), anatomical variants (i.e. skeletally smaller carpal tunnel), intrinsic nerve tumors (perineuriomas, neurolipomatosis), and extrinsic compressive lesions (cysts)
• WMS is a genetic connective tissue disorder with manifestations including brachydactyly, camptodactyly, thickened skin, ocular abnormalities and short stature
• Mutation of ADAMTS10 can cause aberrant fibrillin microfibrils and lead to tenosynovial thickening which can compress the median nerve within the carpal tunnel
• Identifying WMS as the etiology for CTS has significant implications on management, particularly when considering surgical options. Open carpal tunnel release is the most common approach for children with CTS, and in the case of MPS, early intervention may improve functional outcomes. However, due to the relative rarity of WMS and the underlying structural abnormalities, less is known regarding the outcomes of surgery
• In the case of our patient, surgery provided some improvement seen on NCS and imaging, but she had remaining significant deficits. Potential causes include prolonged nerve compression resulting in no or little reinnervation potential, inadequate decompression, or the nerve being compressed/injured intrinsically. In the case of the latter etiology, secondary surgeries could be considered to improve function (e.g. gain more thumb abduction/opposition)
• Awareness of this diagnosis would allow for better patient counseling and informed management decisions

Deep brain stimulation (DBS) success relies on careful titration of stimulation settings.

There is often a delay between setting changes and visible clinical response.

• Making features like bradykinesia, axial instability, cognitive… difficult to optimally treat during limited clinical visits.

Current trial-and-error optimization can require >1yr of frequent/costly specialist appointments.

An objective rapidly acquired biomarker of stimulation success is desirable.

Together with improved construction of DBS hardware, our group has developed and tested a safe fMRI acquisition protocol during stimulation.

Uses the standard Medtronic programmer and MRI operational software. No special equipment required.
 

Optimal stimulation settings result in an identifiable pattern of functional network engagement. 

Acute changes fMRI response is predictive of long-term outcome, preceding changes in symptoms that may take hours/days to reappear.

Prospectively compare fMRI-based stimulation optimization with >1yr of standard-of-care (SoC) programming in a double-blind, crossover, non-inferiority trial.

22 PD STN-DBS subjects prospectively enrolled for fMRI prior to SoC stimulation optimization.

1. Data suggests fMRI-based programming may be non-inferior to conventional clinical programming.
2. Tremor improvement may be better with SoC programming. However, improvements in bradykinesia and axial instability may be better with fMRI.
3. Equivalent overall outcomes may be achieved in 3hrs of early post-op fMRI vs 1yr SoC.

• Degenerative Cervical Myelopathy (DCM) is the most common form of non-traumatic spinal cord injury worldwide [1].
• DCM diagnosis implies a neurological impairment due to spinal cord compression from degenerative breakdown of spinal structures [2].
• Neurological symptoms include: gait imbalance, numbness in the hands, sphincter dysfunction, and pain in the upper extremities [3].
• The only current treatment for DCM that is symptomatically progressive or severe is surgery.
• It is unclear whether patients exhibiting mild symptoms (mild DCM) will benefit from surgery or not. Most mild DCM patients are non-operatively managed.
• There is a large gap in clinical literature surrounding whether surgery will benefit patients with mild DCM.
• Purpose: We aim to develop a supervised machine learning model capable of identifying mild DCM patients at risk of neurological deterioration.

• 49 mild DCM patients underwent MRI scans, including T2w, diffusion tensor imaging (DTI), and magnetization transfer (MT) scans, along with a series of clinical metrics.
• Quantitative MRI metrics were derived above and below the maximally compressed cervical level.
• Random forest classifier, support vector machine, and logistic regression models were trained and tested to predict six-month neurological deterioration
• SHAP and LIME model interpretation were used to extract feature importance at the global and local level

• The best-performing models consistently contained the dataset with a combination of qMRI-derived and clinical metrics.
• MTR in the dorsal and ventral funiculi showed greater importance to model performance than DTI metrics.
• A vast majority of metrics were redundant, with ~32 of 171 being the most important unique metrics.

• Mild DCM patients would benefit from MT scans to assess the degree of demyelination, particularly rostral to the point of compression.
• Decreased MTR in the dorsal/ventral funiculi in combination with moderate tingling in the arm, should, or hand acts as an indicator for six-month neurological deterioration in mild DCM.
• Further validation of the proposed model on a multi-center, national dataset is needed.

1. Fehlings, M. G. et al. A global perspective on the outcomes of surgical decompression in patients with cervical spondylotic myelopathy: results from the prospective multicenter AOSpine international study on 479 patients. Spine 40, 1322–1328 (2015).
2. Nouri, A., Tetreault, L., Singh, A., Karadimas, S. K. & Fehlings, M. G. Degenerative Cervical Myelopathy: Epidemiology, Genetics, and Pathogenesis. Spine 40, E675-93 (2015).
3. Davies, B. M., Mowforth, O. D., Smith, E. K. & Kotter, M. R. Degenerative cervical myelopathy. BMJ 360, k186 (2018).

Contact: Abdul Al-Shawwa, abduljawwad.alshawwa@ucalgary.ca

Early postoperative CT (EPCT) head imaging

• Computed tomography (CT) head scan within 24 hours of brain surgery (i.e., craniotomies)
  • Used to detect surgical complications (e.g., bleeding, ischemia)
  • For QI purposes (e.g., residual subdural hematoma or tumor)
• Problems with EPCT
  • Resource intensive
  • Transfer risk to unstable patients (i.e., ICU patients, EVD dislodgement)
  • Radiation exposure
• EPCT in the literature
  • Optimal timing of postop CT head – Scans performed 0-7h postop failed to predict CT changes that may develop over time or impact medical management (Khaldi et al., 2010)
  • EPCT following elective craniotomy in neuro-preserved patients is not supported (Blumrich et al., 2021)
  • Failure to extubate within 1h warrants EPCT due to increased risk of repeat surgery (Schär et al., 2016)

STUDY QUESTION & OBJECTIVE

Postoperative cranial neurosurgical imaging practices are highly variable

• Study Question: Does routine early postoperative computed tomography (EPCT) change management?
• Objective: To evaluate the rate and utility of EPCT, defined as a CT head scan within 24 hours of brain surgery, in consecutive adult craniotomies

METHODS

Review of postop CT head use

• Review of electronic medical records
• Adult neurosurgical patients admitted to the University of Alberta
• Consecutive craniotomies performed >1 year ago
  • Excluded surgeries: Non-craniotomies, mini craniotomies for biopsy, craniectomies, cranial burr holes for hematoma evacuation
• Extracted data:
  • Rate, timing, and utility (rate of unexpected/adverse findings) of EPCT
  • Rate of surgical complications, neurologic deterioration, and the need for further surgical intervention
  • Collected from progress notes, operative notes, and radiology reports

2. Early postop CT head is routine practice

• Identified N=56 (35.9%) craniotomies of 156 neurosurgical procedures
  • 27 female; avg age 55.5 ± 2.1 years, range 19-84 years
• All patients underwent EPCT
  • POD 0 = 10/56 (17.9%)
  • POD 1 = 46/56 (82.1%)

STUDY LIMITATIONS

• Small sample size
  • An additional 444 craniotomies (N=500 total) will be evaluated
• Single-centre study
  • Surgeon-specific post-operative neuroimaging practices may skew results
• One data extractor
  • Unable to assess inter-rater reliability
• Retrospective (vs. prospective) design

CONCLUSIONS

May omit EPCT if neurologically intact

• Low rate of repeat surgery in the absence of neuro deficits despite abnormal EPCT
• Routine EPCT may not be justified in the absence of clinical deterioration

Significance

• Improve patient safety (i.e., minimize radiation exposure, limit transfer risk of unstable patients)
• Optimize resource allocation
• Decrease healthcare spending

Blumrich et al. Routine postoperative CT scan after craniotomy. Neurosurg Rev. 2021 Oct;44(5):2523-2531.
Khaldi et al. Clinical significance and optimal timing of postoperative CT. J Neurosurg. 2010 Nov;113(5):1021-5.
Schär et al. No routine postoperative head CT following elective craniotomy. PLoS One. 2016 Apr 14;11(4):e0153499.

• Frontotemporal dementia (FTD) is a common cause of presenile dementia, which presents with heterogeneous combinations of behavioral, language and motor symptoms.[1]  Approximately 40% of all FTD cases are familial, with ~10% of the total cases caused by autosomal dominant mutations in one of the microtubule associated protein tau (MAPT), chromosome 9 open reading frame 72 (C9orf72), or progranulin (GRN) genes.[1]
• Neuropsychiatric symptoms (NPS) often begin prior to the onset of FTD, and progress throughout the stages of FTD.
• Particularly, familial FTD due to autosomal dominant genetic mutations might display genetic variant-specific NPS profiles.
• We hypothesized distinct rates of change in NPS ratings scales among C9orf72, GRN, and MAPT mutation carriers during their transition from presymptomatic to symptomatic stages of FTD.

• Participants were recruited through the ARTFL-LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) Study. All participants provided informed consents.
• The participants underwent genetic testing for mutations associated with FTD, including C9orf72, GRN, and MAPT. They also underwent annual neurologic examinations, cognitive, neuropsychological, and MRI assessments.
• Follow-up duration ranged from 2-5 years (two to five visits per participant).
• Conversion was defined as reaching the CDR-plus-NACC-FTLD global score 1, during follow-up.
• We included N=1662 participants, with 342 C9orf72, 148 GRN, 168 MAPT mutation carriers, and 1004 noncarriers.

• We used the CDR plus NACC FTLD global scores to define the conversion status, and stratified participants into four stages of progression:

1. Presymptomatic (CDR=0 throughout the follow-up; N=559),
2. Early conversion (began with CDR=0, then increased to 0.5 during the follow-up; N=33),
3. Advanced conversion (began with CDR=0.5, then increased to 1.0 or above; N=56),
4. Symptomatic (CDR>1.0 throughout; N=1024).

• We used the Neuropsychiatric Inventory Questionnaire (NPI-Q) to assess the changes in NPS.[2]
• We analyzed the NPI-Q total scores and the following NPI-Q subsyndromes, adapted from Aalten et al., Dem Geriatr Cogn Disord 2007 [3]:
  • Hyperactivity (Agitation, Disinhibition, Irritability, Aberrant Motor Behavior)
  • Affective (Anxiety, Depression)
  • Psychosis (Delusions, Hallucinations, Nighttime Behavior)
  • Apathy (Apathy, Appetite)

• We used generalized linear mixed models to compare the rates of NPI-Q score changes among C9orf72, GRN, MAPT mutation carriers, and noncarriers.
• The models were adjusted for age, sex, education, and baseline NPI-Q scores. Years from baseline was used as the time variable.

• NPI-Q trajectories were similar among carriers and noncarriers during presymptomatic stages.
• However, in the early conversion stage, C9orf72 (p=0.04) and GRN (p=0.004) carriers exhibited significantly higher NPI-Q score increases compared to MAPT carriers. During this stage, potential differences were observed in the hyperactivity and psychosis domains.
• In the advanced and symptomatic stages, the rates of NPI-Q changes were similar across the groups.

• This study suggests that people with familial FTD, particularly those predicted to have underlying TDP-43 pathology, may experience faster progression of neuropsychiatric symptoms like psychosis or hyperactivity as they progress from presymptomatic to prodromal phases. The rates of NPI-Q increase during this stage appear faster than those with tau pathology or sporadic FTD.
• Further studies are warranted to understand these unique progression patterns and their implications for FTD management.

• Improvements in cancer survival rates have led to a growing number of cancer survivors within or entering the age range at risk of dementia development.^1,2
• A significant number of cancer patients experience issues with cognitive functions after treatment, known as cancer-related cognitive impairment (CRCI).³
• CRCI may be associated with structural and functional changes in the brain.
• Additionally, CRCI may alter the trajectory of normal aging, and may impact the future risk of developing dementia.

• To summarize the current knowledge on changes in brain imaging, cognitive performance, and the association between cancer survivorship and dementia risk​ in adult non-CNS cancer survivors who received chemotherapy.

• We conducted a PRISMA-guided search on PubMed for primary studies between 2010 and 2023.
• The quality of the eligible studies was evaluated using the National Heart, Lung, and Blood Institute Study Quality Assessment Tools.⁴

 

Imaging Studies

• We observed global changes in gray matter, white matter, and functional networks, with particularly pronounced changes in the frontal, temporal, and parietal regions.

Cognitive Studies

• Cognitive decline was most consistently reported in attention, language skills, and memory, although heterogeneity was greater than that observed among imaging findings.

Dementia risk studies

• ~70% of the studies reported a lower risk of dementia in cancer survivors.

• Significant imaging changes were noted in the studies, particularly in the regions commonly affected in types of dementia such as Alzheimer’s or Frontotemporal dementia.
• Since most studies only had up to 1 or 2 years of follow-up, the evidence is limited for drawing a robust conclusion regarding whether CRCI is reversible or irreversible.
• The 'protective' effect of cancer on dementia should be interpreted with caution, particularly considering whether the follow-up timeframe was sufficient to include long-term (>5 years) survivors.
• Future studies should explore the link between CRCI and dementia risk, examining the influence of cancer type and treatment, genetic predisposition, and lifestyle factors.

Objective:
To study the outcome of patients with psychogenic non-epileptic seizures (PNES) after their diagnosis in the epilepsy monitoring unit (EMU).


Methods:
Patients diagnosed in our EMU with definite PNES between January 2009 and May 2023 were contacted by phone, and those who agreed to participate were asked a set of predetermined questions.
Comparative analyses were carried out on several variables before and after diagnosis:

• number of participants with daily PNES
• number of visits to the emergency department
• number of participants who consulted their general practitioner or a neurologist outside of a scheduled follow-up
• number of participants who took antiseizure medications (ASMs) or psychotropic drugs
• employment status

Results in bullets:

• 103 patients with a definite diagnosis of PNES.
• 61 patients accepted to participate in our study.
• 79% female.
• 35 yo Median age at PNES onset.
• 3 years Median delay to diagnosis.
• 62% receiving ASMs and 40% psychotropic drugs.
• 5 days mean stay at the EMU.
• 89% accepted PNES diagnosis.
• 46% no longer had PNES.
• 32% immediately upon communication of the diagnosis. 
• 51 months median follow-up duration.
• 18 (vs. 38%) patients had daily seizures after the diagnosis.
• Significantly lower ER, GP and neurologists visits.
• 33% (vs 70%) still took ASM, with only one for its antiseizure property.
• 49% (vs 25%) had work.

Conclusion:
Our study revealed a relatively favorable long-term outcome of definite PNES diagnosed in the EMU that translated in significant reductions in PNES frequency, health care utilization and ASM use, as well as a significant increase in employment rate.

• Eptinezumab (Vyepti) is a humanized mAb that specifically targets the CGRP ligand and is indicated for prevention of migraine in adults.¹
• Eptinezumab is administered intravenously (IV),² while other anti-CGRP monoclonal antibodies (fremanezumab/Ajovy,³ galcanezumab/Emgality,⁴ and erenumab/Aimovig⁵) are administered subcutaneously.
• Minimal evidence exists evaluating the real-world effectiveness of switching from a subcutaneous anti-CGRP mAb to an intravenous anti-CGRP mAb.
   

• REVIEW was an observational, multi-site (4 tertiary headache centers), US-based study that evaluated real- world experiences of patients being treated with eptinezumab for chronic migraine (CM) in the outpatient setting as well as the experiences of 4 treating principal investigators.
• Study sites were instructed to select and recruit patients based on the key inclusion/exclusion criteria outlined below:
  • Eligible patients were ≥18 years of age, had a diagnosis of CM (per the patient chart), and had completed ≥2 consecutive eptinezumab infusion cycles (i.e., 6 months’ exposure).
  • Patients were excluded if they were enrolled in a clinical trial or had been treated with eptinezumab in a clinical trial setting (no time limit).
    
     

• Ninety-four patients enrolled (Figure 1).
• Regardless of prior exposure to a CGRP ligand blocker (galcanezumab and fremanezumab) or receptor blocker (erenumab), the number of “good” days per month more than doubled following eptinezumab treatment (Figure 3).
• Regardless of the number of prior subcutaneous anti-CGRP mAbs used, the number of “good” days/month at least doubled following eptinezumab treatment. (Figure 4).

• REVIEW was an observational, multi-site, US-based study that evaluated real-world experiences of patients being treated with eptinezumab for CM.
• The robust response, where the average number of patient-reported “good” days per month at least doubled, was irrespective of the mechanism of CGRP blockade of the previously used subcutaneous anti-CGRP mAb(s). This indicates that the switch from ligand or receptor-targeted therapy did not impact the effectiveness of eptinezumab.
• The effectiveness of eptinezumab in improving “good” days did not differ regardless of the number of previous treatments with subcutaneous anti-CGRP mAbs, suggesting that a positive response can be attained upon transitioning to IV eptinezumab without the need for multiple trials of subcutaneous anti- CGRP mAbs, thereby reducing the time to effectiveness and minimizing exposure to multiple agents in this class.

This real-world, patient survey showed that patients with prior exposure to subcutaneous anti-CGRP mAbs had high overall improvement in “good” days with eptinezumab treatment regardless of the number and type of previous anti-CGRP therapies used.
 

• Eptinezumab is an anti–calcitonin gene-related peptide monoclonal antibody (anti-CGRP mAb) indicated for the preventive treatment of migraine,¹ with its efficacy and safety in adults demonstrated in multiple large-scale clinical trials.^2–5
• In the DELIVER study, eptinezumab treatment resulted in statistically significant reductions in MMDs compared with placebo in patients with migraine and 2–4 prior preventive treatment failures.⁵
• Failure of multiple therapies is often required before receiving anti-CGRP mAb treatment; however, guidelines for how many and which therapies must fail vary by country and payor.^6–9

To evaluate the efficacy of eptinezumab versus placebo across 24 weeks of treatment in the DELIVER study in subgroups defined by type of prior treatment failure

• DELIVER (NCT04418765) was a phase 3b, multicenter, parallel-group, double-blind study that randomized patients to eptinezumab 100 mg, 300 mg, or placebo via intravenous infusion every 12 weeks.⁵
• Eligible patients (aged 18–75 years) with episodic or chronic migraine needed documented evidence of 2–4 prior preventive treatment failures within the past 10 years.
• Patients may have had prior failures across multiple types of treatment; therefore, subgroups are not mutually exclusive.

• The full analysis set included 890 patients.

• Among patients with previous preventive migraine treatment failures, eptinezumab demonstrated greater reductions in monthly migraine days (MMDs) compared with placebo across all subgroups of traditional preventive treatment types.
• These results suggest that a second dose of eptinezumab may provide additional benefit.
   

• In all subgroups, regardless of prior preventive treatment failure type, eptinezumab demonstrated greater reductions in MMDs and larger migraine responder rates (MRRs) compared with placebo.
• Given the differences in preventive migraine treatment guidelines, it is important that the efficacy of eptinezumab does not appear to be impacted by the type of prior preventive medication that led to treatment failure.

 

To assess the utility of using emergency department data for understanding the relationship between air pollution and migraine.

 

Non-probablily online survey of ER use for migraine in Canada and the USA. Analyzed in R [2].

 

Table 1: Demographic and migraine diagnosis information from eligible participants 

Table 2: Participant’s responses to the question: “Why did you go to or think about going to the Emergency Room?” 

Table 3: Participants’ responses to the question “Why didn’t you go to the Emergency Room when you had a migraine attack?”

Reason for not attending ER	Canada, N = 621	USA, N = 751
Did not need to go to emergency room	13 (21%)	27 (36%)
Avoid long wait time, bright lights, noises and other discomforts	50 (81%)	51 (68%)
Got medical help somewhere else	7 (11%)	7 (9.3%)
Attack ended or got better	13 (21%)	26 (35%)
Too hard to get to ER	6 (9.7%)	14 (19%)
Too expensive	0 (0%)	30 (40%)
Avoid exposure to COVID-19 or other infectious illnesses	19 (31%)	11 (15%)
Other - Fear of or previous experience of ineffective medical treatment	2 (3.2%)	5 (6.7%)
Other - Fear of or previous experience of unkind treatment from staff at ER	1 (1.6%)	4 (5.3%)
1n (%)

1.  James SL, Abate D, Hassen Abate K, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, a systematic analysis for the Global Burden of Disease Study 2017. The Lancet. 2018; 392(November): 1789-1858. 
2. Portt AE, Orchard C, Chen H, Ge E, Lay C, Smith PM. Migraine and air pollution: A systematic review. Headache. 2023; 63(9): 1203-1219. 
3.  Minen MT, Loder E, Friedman B. Factors associated with emergency department visits for migraine: An observational study. Headache. 2014; 54(10): 1611-1618.
4. R Core team. R: a language and environment for statistical computing. Version 2024.04.0+735. https://www.r-project.org

Email: andrea.portt@mail.utoronto.ca

Background

Neuroimaging is not warranted in migraine patients who have a normal neurologic examination, and there are no atypical features or red flags present. Grade A.
Neuroimaging may be considered for unusual, prolonged, or persistent aura; increasing frequency, severity, or change in clinical features, first or worst migraine, migraine with brainstem aura, migraine with confusion, migraine with motor manifestations (hemiplegic migraine), late-life migraine accompaniments, aura without headache, side-locked headache, and posttraumatic headache. Most of these are consensus based with little or no literature support. Grade C.
Evans RW et. al. Neuroimaging for Migraine: The American Headache Society Systematic Review and Evidence-Based Guideline. Headache 2020;60:318-336.

Methods

Retrospective chart review of 100 headache patients referred to an outpatient neurology practice. We evaluated the use of CT and MRI imaging prior to referral to Neurology and the impact of neuroimaging on clinical management.

Results

Conclusions

Neuroimaging overuse might reflect:

Resources to help improve public and physician awareness regarding neuroimaging use in patients with stable headache may help reduce unwarranted imaging studies and could have significant financial savings for healthcare systems.
 

Progressive supranuclear palsy (PSP) is a neurodegenerative disease classically presenting with parkinsonism, vertical gaze palsy, and cognitive decline.¹ Since its initial description in 1964 (Steele-Richardson-Olszewski), multiple subtypes have been described.² Postural instability is a common symptom of PSP.³ Spontaneous retropulsion involves loss of balance without external provocation. Others have reported on retropulsion in the clinical setting while testing for postural instability,^{4, 5} but rates of spontaneous retropulsion in the community have not been described.

Clinical diagnostic accuracy of PSP approaches 80%⁶ with the most recent diagnostic criteria boasting a sensitivity and specificity of 88% and 86%² respectively. Despite increasing accuracy of recent diagnostic criteria, 20% of PSP diagnoses are incorrect⁶ which impacts clinical reports in the PSP literature. Most studies use patients with clinical diagnoses of PSP without pathological confirmation. Definite diagnosis of PSP requires brain autopsy, and studies with autopsy confirmed PSP therefore provide the highest degree of diagnositc accuracy.

This study aims to report on the prevalence of spontaneous retropulsion in PSP, and identify variables that may be associated with that phenomenon.  The data for this study was gathered exclusively from the charts of patients with clinical and pathology-confirmed PSP.

All PSP cases assessed at the Saskatchewan Movement Disorders Program (SMDP) clinics between 1968 and 2022 with brain autopsy were considered. A retrospective chart review examined 60 patients from the SMDP with clinical and pathology-confirmed diagnosis of PSP. Information regarding patient falls were collected at each clinic visit. We identified patients who endorsed spontaneous retropulsion. The data was analysed with univariate logistic regression.

Every patient assessed in clinic has a choice of autopsy study at no cost to the family or the estate of the patient. Regardless of the wish of the patients, the autopsy decision is made by the next-of-kin after death of the individual. Movement disorders neurologists are on 24/7 call for autopsy. Typically, the neurologist is contacted by the family/caregiver soon after the death to inform that the family wants an autopsy study. 

The neurologist secures autopsy consent and arranges coordination between family, funeral home and pathology department to ensure that the autopsy is done within 24 hours of death. Immediately after the autopsy, the brain is divided at midline. One-half is frozen at -80^oC. The other half is fixed in formalin and studied by a Canadian certified neuropathologist. Final diagnosis is made by the treating neurologist, considering the clinical information and pathology findings.

Consent for autopsy is approved by Saskatchewan Health Authority and the use of brain tissue for diagnosis and research is approved by the Bioethics Board of the University of Saskatchewan.

This study included 43 males and 17 females. Spontaneous retropulsion was reported in 18 (30%) patients. For categorical and continuous variables, chi-squared and Mann Whitney U tests were conducted respectively. Among the variables, only sex showed a statistical significance (p = 0.0184) with females more likely to report spontaneous retropulsion (OR = 4.25). Other variables (PSP onset age, onset age of balance impairment, gait impairment, and disease duration) were not statistically significant. Multivariate analysis was performed but did not identify significant findings.

Our data suggest that spontaneous retropulsion is common in PSP (30% of our patients), with females being at a significantly higher risk than males. This is useful information when counselling patients on risk-avoidance behaviour to prevent falls. It may also help with selection of ambulatory devices and influence the training of patients to use these devices to compensate for the risk of spontaneous retropulsion.

Future direction will include analysis of the prevalence of spontaneous retropulsion in Parkinson disease and other non-PSP forms of parkinsonism. In addition, sub-analysis of the PSP cases in this study may provide further insight. Retroactive application of the 2017 MDS diagnostic criteria for PSP may reveal subtypes of PSP that are more likely to exprience spontaneous retropulsion.

1. Steele JC., Richardson JC, Olszewski J. Progressive Supranuclear Palsy. A Heterogeneous degeneration involving the brain stem, basal ganglia and cerebellum with vertical gaze and pseudobulbar palsy, nuchal dystonia and dementia. Arch Neurol. 1964;10:333. doi: 10.1001/archneur.1964.00460160003001.

2. Höglinger GU, Respondek G, Stamelou M, et al. Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria. Mov Disord. 2017;32:853–64. doi: 10.1002/mds.26987.

3. Birdi S, Rajput AH, Fenton M, et al. Progressive supranuclear palsy diagnosis and confounding features: report on 16 autopsied cases. Mov Disord. 2002;17:1255–64. doi: 10.1002/mds.10211.

4. Borm CDJM, Krismer F, Wenning GK, et al. Axial motor clues to identify atypical parkinsonism: A multicentre European cohort study. Parkinsonism Relat Disord. 2018;56:33–40. doi: 10.1016/j.parkreldis.2018.06.015.

5. Geroin C, Nonnekes J, Erro R, Camozzi S, Bloem BR, Tinazzi M. Shoulder‐touch test to reveal incongruencies in persons with functional motor disorders. Eur J Neurol. 2022:3508-3512. doi: 10.1111/ene.15532.

6. Osaki Y, Ben-Shlomo Y, Lees AJ, et al. Accuracy of clinical diagnosis of progressive supranuclear palsy. Mov Disord. 2004:181–9. doi: 10.1002/mds.10680.

 

We wish to acknowledge the members of the neuropathology division at the University of Saskatchewan for their timely and meticulous assessment of autopsy cases for the SMDP. We also acknowledge the maintenance staff at Royal Univerisity Hospital for their time and effort spent for upkeep of the SMDP laboratory.


 

• To compare the long-term efficacy of INEB treatment in the N-MOmentum open label extension period (OLP) to historical controls treated with AZA or other ISTs as well as to no treatment.

INTRODUCTION

Poster presented at CNSF 2024, May 20-26, Toronto, Canada.

METHODS

• N-MOmentum (NCT02200770) consisted of a 28-week randomized-controlled period (RCP). Participants in the RCP who had an adjudicated attack, completed the RCP, or were in the RCP when enrollment stopped were able to enter an into the OLP in which all participants received treatment with INEB (300 mg every 6 months) for at least 2 years.⁷
• In the absence of a direct PBO arm or IST comparators in the OLP, we used historical data to evaluate the long-term comparative efficacy of the INEB monotherapy.
• Historical comparator groups were derived using data from published NMOSD studies to evaluate the comparative efficacy of INEB treatment (AQP4+ subgroup; N=208) over the OLP. Data from untreated patients was pooled from the observational study of AZA in NMOSD¹¹ that was used to model the sample size from N-MOmentum as well as two contemporaneous PBO treated arms from the PREVENT⁸ study of eculizumab and the SAkuraStar⁹ study of satralizumab. Data from patients treated with AZA or other broad spectrum oral ISTs was pooled from the observational study of AZA in NMOSD, PREVENT and the SAkuraSky study of satralizumab in NMOSD (Table 1).
• Hazard ratios (HR) for the INEB group versus historical comparator groups were estimated using Cox proportional hazards regression.
• Time to NMOSD attack was modelled using parametric and flexible survival (spline) models that were fit to the INEB group and historical comparator groups. Model selection was determined by testing the Cox proportional hazards and accelerated failure time assumptions as well as assessing Akaike’s information criterion/Bayesian information criterion, visual fit, estimated attack-free survival at 4 years, and clinical validation.

RESULTS

CONCLUSIONS

OBJECTIVE
To evaluate long-term outcomes of INEB treatment in AQP4+ NMOSD participants from the N-MOmentum trial with a history of immunosuppressant therapy with azathioprine (AZA) and/or mycophenolate mofetil (MMF) as compared to those without.

• Inebilizumab (INEB), an anti-CD19 B cell-depleting antibody, is approved for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adults seropositive for aquaporin-4 antibody (AQP4+).
• The safety and efficacy of INEB in NMOSD was assessed in the N-MOmentum (NCT02200770) study.¹
  • In N-MOmentum, INEB reduced the risk of an adjudicated NMOSD attack by 77% compared with placebo.¹
  • INEB was generally well tolerated and reduced disability worsening, magnetic resonance imaging (MRI) lesion activity and NMOSD-related hospitalizations compared with placebo.¹
  • The benefits of INEB were maintained with long-term treatment.^2,3
• Immunosuppressants were prohibited during the N-MOmentum pivotal trial, although many participants had a history of immunosuppressant therapy before enrollment.

METHODS

• N-MOmentum (NCT02200770) was a double-blind, placebo controlled, randomized phase 2/3 trial that assessed the efficacy and safety of INEB in adults with NMOSD, and comprised two periods:
  • Randomized control period (RCP; 3:1 to INEB [intravenous, 300 mg] or placebo) for 28 weeks or to an adjudicated attack
  • Optional open-label period (OLP; INEB every 6 months) for ≥2 years
• N-MOmentum included adults with NMOSD who had received treatment for ≥1 attack in the past year or ≥2 attacks in the past 2 years, and who had an EDSS score ≤8.0.
  • The primary endpoint was time to first adjudicated attack during the RCP.
  • Secondary endpoints included the annualized attack rate (AAR), disability progression assessed via the expanded disability status scale (EDSS), and number of NMOSD-related inpatient hospitalizations.
  • Safety assessments included treatment-emergent adverse events (TEAEs) and treatment-emergent adverse events of special interest (AESIs).

Poster presented at CNSF 2024, May 20-26, Toronto, Canada. 

• Immunosuppressant medication for the prevention or treatment of NMOSD relapses was allowed prior to dosing on Day 1 but prohibited during the trial.
• In this post hoc analysis, AQP4+ participants were grouped by no prior immunosuppression therapy beyond treatment of acute NMOSD attacks (naive), or prior azathioprine (AZA) and/or mycophenolate mofetil (MMF) therapy.
• Outcomes assessed for these two groups included: AAR, Disability progression (EDSS), NMOSD-related inpatient hospitalizations, safety assessments 

RESULTS
Participants

• Among participants who received any INEB during the OLP, a total of 94 had received prior AZA/MMF treatment and 103 were immunosuppressant naïve before entering the study.
• Participants in the immunosuppressant naïve group had an overall shorter duration of disease and faster time to first INEB administration.

NMOSD Attack

• During the RCP, fewer participants in both the prior AZA/MMF group and the immunosuppressant naïve group having received treatment with INEB had an adjudicated attack compared with those receiving placebo.
• The total patient-years of INEB treatment in the prior AZA/MMF group was 300.35 and for immunosuppressant naïve participants, 335.7.
• The AAR (95% confidence interval [CI]) for participants with prior AZA/MMF treatment was 0.11 (0.07, 0.17), compared to 0.08 (0.05, 0.14) for the immunosuppressant naïve group.

REFERENCES
1. Cree BAC, et al. Lancet. 2019;394:1352-63. 
2. Cree BAC, et al. Poster A-21-00375 presented at EAN 2021. 
3. Cree BAC, et al. Poster P2283 presented at AAN 2021.

• All participants receiving INEB had a high probability of remaining attack-free over time.
• When stratified by year, the AAR was low and similar for participants having received INEB in the prior AZA/MMF treatment group and the immunosuppressant naïve group.

Disability Progression

• During RCP, a smaller proportion of participants had EDSS score worsening with INEB treatment vs placebo in both participants receiving prior AZA/MMF treatment (19.2% vs 43.5%) and those in the immunosuppressant naïve group (13.6% vs 28.0%).
• Stabilization of EDSS score was seen in both groups throughout the OLP. 

• During RCP, a smaller proportion of participants had NMOSD-related inpatient hospitalizations with INEB treatment vs placebo in both those having received prior AZA/MMF treatment and those in the immunosuppressant naïve group.

• Through the OLP, a similar number of inpatient hospitalizations were observed in the prior AZA/MMF group (40) and the immunosuppressant naive group (40).
• The annualized NMOSD-related inpatient hospitalization rate (annualized rate [95% CI]) for prior AZA/MMF treatment was 0.15 (0.08, 0.27), and 0.12 (0.06, 0.22) for immunosuppressant naïve participants.

Safety

• The percentage of participants with ≥1 study drug-related TEAE was 30.9% (29/94) in the prior AZA/MMF group and 46.6% (48/103) in the immunosuppressant naive group; 4.3% (4) of prior AZA/MMF and 5.8% (6) of immunosuppressant naive reported ≥1 study drug-related serious adverse event.
• Most adverse events were infection-related for both groups; (72.3% (68/94) for prior AZA/MMF and 76.7% (79/103) for immunosuppressant naive).

CONCLUSION Outcomes of INEB in AQP4+ NMOSD participants that received prior AZA and/or MMF therapy demonstrated a similar efficacy/safety profile. 

• Anti-aquaporin-4 antibody-positive (AQP4-Ab+) neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease of the central nervous system characterized by repeated, unpredictable relapses, leading to accumulation of irreversible neurologic disability^1,2
• In the phase 3 PREVENT trial, the C5 inhibitor therapy eculizumab was well tolerated and reduced the risk of relapse in patients with AQP4-Ab+ NMOSD by 94.2% relative to placebo (Figure 1)³
  • Results of this trial led to approval of eculizumab to treat AQP4-Ab+ NMOSD in adults in numerous countries and regions, including Europe, Japan, and the US^4-6
• Ravulizumab was developed from and binds to the same C5 epitope as eculizumab but has a longer elimination half-life, enabling an extended dosing interval of every 8 weeks instead of every 2 weeks (Figure 1)⁷
  • Ravulizumab is also approved to treat AQP4-Ab+ NMOSD in adults in numerous countries and regions, including Europe, Japan, and the US^8-10

• To report the interim efficacy and safety of ravilizumab from the last data cut (June 16, 2023) of the long-term extension (LTE) period of the CHAMPION-NMOSD trial (NCT04201262) of ravulizumab in patients with AQP4-Ab+ NMOSD

• CHAMPION-NMOSD is a phase 3 pivotal, global, open-label trial of ravulizumab in patient swith AQP4-Ab+ NMOSD (Figures 2 and 3)
  • The study used the placebo group from the PREVENT trial

• Baseline demographics and clinical characteristics of participants treated with ravulizumab (n=58) were similar to those in the placebo group in PREVENT (n=47) (Table 1)
• In the PTP, median (range) follow-up was 73.5 (11.0–117.7) weeks (84.0 patient-years) for ravulizumab and 36.0 (1.9–117.7) weeks (46.9 patient-years) for placebo in PREVENT

• Of the 58 patients being treated with ravulizumab in the PTP, 56 entered and 2 have completed the LTE as of the cutoff of June 16, 2023, with median (range) follow-up of 138.4 (11.0–183.1) weeks (153.9 patient-years)
  • In the external placebo comparator group (n=47), median (range) duration of follow-up was 36.0 (1.9–183.1) weeks
• Across the PTP and LTE, no patients had an adjudicated on-trial relapse during ravulizumab treatment (153.9 patient-years of follow-up), corresponding to a 98.9% reduction in the risk of relapse with ravulizumab versus placebo (log-rank P<0.0001) (Figure 4)
  • Median (range) follow-up of 138.4 (11.0–183.1) weeks for ravulizumab (n=58) and 36.0 (1.9–183.1) weeks for placebo (n=47). Patients may have transitioned to the extension period as early as 52 weeks
• HAI scores remained stable or were clinically improved in 91.4% (53/58) of patients treated with ravulizumab from baseline to the LTE cutoff (Figure 5)
• 91.4% (53/58) of patients had no clinically important worsening in EDSS score with ravulizumab from baseline to the LTE cutoff (Figure 6)

• No new safety signals were observed in the LTE (includes 69.9 patient-years of follow-up)
• During the PTP, 2 vaccinated patients developed meningococcal infections during the PTP; both received antibiotics and intensive care and recovered with no sequelae (Table 2)
  • One patient withdrew, and 1 remains in the trial

• During the LTE, no meningococcal infections occurred as of the cutoff
• One death, occurring during the LTE, was later updated to hypertensive heart disease after the data cut and assessed by the investigator as unrelated to ravulizumab

• During a median (range) follow-up of 138.4 (11.0–183.1) weeks across the PTP (84.0 patient-years) and LTE (69.9 patient-years), no patient treated with ravulizumab experienced an adjudicated relapse
• Most patients treated with ravulizumab demonstrated stable or improved disability measures through the longer-term 138.4-week median follow-up that included the PTP and LTE
• The safety profile presented here is consistent with that observed in prior analyses, and notably no new meningococcal infections were observed beyond the 2 reported during the PTP
• Together, these findings demonstrate the long-term clinical benefit of ravulizumab in the prevention of relapses in patients with AQP4-Ab+ NMOSD

• Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease of the central nervous system characterized by repeated, unpredictable relapses, leading to accumulation of neurologic disability and reduced health-related quality of life^1-3
• The complement component 5 inhibitor therapies (ALXN-C5ITs) eculizumab and ravulizumab have received or have been submitted for regulatory approval in several regions for the treatment of anti-aquaporin-4 antibody-positive (anti-AQP4+) NMOSD^1,4
• In the phase 3 PREVENT study in patients with anti-AQP4+ NMOSD, eculizumab was associated with a 94.2% reduction in NMOSD relapse risk compared with placebo⁴
• In the phase 3 CHAMPION-NMOSD study in patients with anti-AQP4+ NMOSD, ravulizumab demonstrated a 98.6% reduction in risk of adjudicated on-trial relapse compared with external placebo¹
• Real-world effectiveness and safety data from patients with anti-AQP4+ NMOSD treated with the ALXN-C5ITs are needed to supplement the existing body of scientific evidence and to better inform clinical practice

• To present the study design of the NMO SPOTLIGHT Registry (NCT05966467),⁵ which will assess the long-term safety, clinical effectiveness, and real-world impact of the ALXN-C5ITs eculizumab and ravulizumab in adults with anti-AQP4+ NMOSD

• This global, long-term, prospective, multicenter, observational registry will enroll approximately 130 patients, with a maximum of approximately 200 patients in up to 15 countries globally (Figure 1)
• Data will be collected retrospectively from 1 year prior to ALXN-C5IT initiation through registry enrollment and prospectively for up to 5 years after enrollment for each patient; clinical data will be collected at least once annually and patient-reported outcomes data at least every 6 months (Figure 2)
• Data will be reported using descriptive statistics

Inclusion Criteria

• Age ≥18 years
• Confirmed diagnosis of anti-AQP4+ NMOSD
• Receipt of treatment with ALXN-C5IT (≥1 dose) according to approved local prescribing information
  • Eculizumab within the past 4 weeks OR
  • Ravulizumab within the past 12 weeks
• Available historical data
  • ALXN-C5IT dosing information since initiation
  • Number and types of relapses from 1 year prior to ALXN-C5IT initiation through registry enrollment

Exclusion Criteria

• Current enrollment or participation in an interventional clinical study for the treatment of anti-AQP4+ NMOSD in which the intervention is a drug

Virtual neurological assessments were particularly useful and increasingly used during the COVID-19 pandemic.1,2 Neurological assessments may be limited when the physical examination is not performed in person.

To analyze the accuracy of video and telephone consultations in the setting of an outpatient neurology clinic when compared to in person assessments.

   

Clinical records were reviewed retrospectively at Sunnybrook Health Sciences Centre in a general neurology outpatient clinic, with predominantly MS patients (See Table 1) from March 23rd 2020 to March 23rd 2021 during the peak of the COVID-19 pandemic
1036 patients were analyzed with an initial virtual assessment and subsequently in person when COVID-19 restrictions were lifted or when patients were brought in on an urgent basis
“Clinical disparities (DISP)” were defined as:
(a) patients reporting progression virtually, but found no significant changes on exam with an alternative explanation for complaints
(b) patients reporting stable virtually, but found significant changes on in person exam
“Clarified” was defined as in person exam confirmed virtual reported findings and helped to clarify management

See Table 1 for pathologies. Of 1036 patients included in this study, 27.8% (n=288) of consultations were with video and 72.2% (n=748) with telephone. A total of 13.8% (n=143) of virtual consultations were considered DISP, specifically 13.5% (n=39) video and 13.9% (n=104) telephone consultations. Of the DISP cases, 2.32% (n=24) of all patients stated they were stable but significant changes were seen with in person exam. 3.38% (n=35) of patients stated they were rapidly deteriorating virtually but were stable in person. In person assessments confirmed 13.0% (n=135) of patients’ worsening symptoms virtually or helped to clarify management decision. See Figure 1.

Virtual assessments demonstrate to be helpful for most patients in an outpatient neurological setting during the pandemic in over 85% of cases. However, it should be noted that the in person neurological exam led to a change in clinical opinion in 13.8% of assessments. The importance the neurological exam in person was particularly important in 2.32% of patients who described clinical stability but led to different clinical management plans with significant exam findings not identified virtually, including subtle weaknesses, abnormal reflexes, sensory changes, and non-organic findings.

Intravenous Immunoglobulin (IVIg) use for Central Nervous System (CNS) conditions has increased over the last decade. In many CNS disorders, robust evidence for IVIg efficacy is still lacking. Building on the success of the British Columbia (BC) Neuromuscular IVIg utilization initiative, Guidelines for IVIg use in CNS conditions were developed. A provincial screening program was launched in 2023.

• IVIg may be effective in the management of some CNS inflammatory conditions
• A physician-led utilization program with targeted education to ordering physicians promotes best practice
• In over 50% of cases reviewed, alteration of IVIg dose was recommended, illustrating the potential impact of screening programs to optimize the judicious use of this limited resource
• lessons learned from the pilot screening program will inform future versions of provincial guidelines and the screening process

BACKGROUND
Vestibular schwannoma are benign nerve sheath tumours that arise from the vestibulocochlear nerve within the internal auditory canal (IAC) and extend into the cerebellopontine angle (CPA), where they can cause worsening clinical presentation. It is the most common tumour of the CPA with an annual incidence of 17.4/1 million. They typically demonstrate slow growth over time and as such, a reasonable approach to management of these tumours is observation. A portion of these tumours remain static and approximately 5-10% of these tumours will demonstrate spontaneous regression without intervention while under observation, including those associated with neurofibromatosis type-2. The standard treatment is surgical resection followed by radiation for residual tumour or reoccurrence, however, management recommendations encourage tailoring of care to each patient and tumour individually.
Several previous case series have attempted to create predictive models both of tumour growth and regression, but few have reached statistical significance or demonstrated reproducible findings.  If factors were identified that could predict tumour growth, one could identify those who will require intervention at an earlier stage of the disease. One meta-analysis conducted on tumours that demonstrated growth identified that size at diagnosis was the only predictive factor that reached significance.  In a similar vein, defining factors that reliably predicted patients who would experience spontaneous regression could prevent future patients from undergoing unnecessarily aggressive interventions.  As per our review of the literature, no patient characteristics have yet predicted spontaneous regression to date. Imaging characteristics including a festooned aspect of the tumour and the presence of cerebrospinal fluid in the IAC have been identified as predictive for tumour regression in small case series (N=13-14). 

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METHODS
Using a clinical database of acoustic schwannomas treated by one team at our institution, we identified approximately 40 patients who have demonstrated significant spontaneous regression or complete resolution of their acoustic schwannoma. All patients recieved a survey by mail and were contacted by telephone to complete the survey. For all patients who consented to participate, radiographic and clincal data was collected from patient charts in addition to survey responses.  Medical comorbidities and medications were provided through patient questionairre and cooroberated with patient charts. Tumour volume was approximated using the formula V=4/3*pi*length/2*width/2*height/2. A nominal logistic regression was completed using JMP v17, with 50% tumour reduction set as the reference value. 

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RESULTS
12 patients returned the survey. Two patients returned the questionnaire without the consent form and were therefor excluded. 10 patients were included in the final descriptive summary of this patient population. Tumours were generally small, L-sided (8/10), with a fungated shape (6/10), and at least partial preservation of CSF in the IAC (8/10).  Significant decreases in tumour volume were used to identify and include patients in the study, however, no patient factors or radiographic factors appeared to predict the degree of tumour regression. 

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CONCLUSION
In conclusion, this is the first study to summarize patient lifestyle factors obtained through patient survey in addition to clinical and radiographic factors to describe spontaneous regression of acoustic schwannoma. No obvious clinical factors appear to be protective based on this preliminary data. No imaging characteristics, including those previously demonstrated to be predictive, such as CSF preservation in the ICA and ICA extension are predictive in this study. A case-control study including control patients who demonstrated tumour progression should be completed in future.

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Background

• Health education suffers from a lack of diverse representation both in how it frames expertise and who is physically represented in curricular content
• Our project aims to address both issues by
  • acknowledging patient and student expertise
  • demonstrating a common health care procedure (lumbar punctures) across diverse bodies

Methods

• Interviewed patients using trauma-informed methods
• Captured Lumbar Puncture instructional videos with diverse standardized patients
• Invited Biomedical Communications students to paint spinous processes on the backs of patients
• Compiled patient stories, videos, and images into a teaching module

Patients as Experts

We interviewed five (5) stroke patients and their families to understand the patient experience of lumbar punctures. Patients are experts in how they experience health care and interactions with health care practitioners. From their stories, we learned valuable lessons on how LPs can be done in a more patient-centred way.

Communication is key

“So verbal communication when you're doing it is definitely a way to put patients at ease…. You know those kind of reassuring things are very important to the patient.”
– Sandy, LP Patient

Know when to seek help

“This is years later, so it just strikes me as as it's it is really important that if you can't get it right right away, don't try and force the issue right…. Either try something a little bit different, or get someone to help and maybe tell the person that's laying on the table.”
– Jim, LP Patient

Show confidence

“as she told me about the procedure that was going to happen and all the stuff she do it was every time she'd say something she's gonna do she said we'll try to do it or I should be able to do this and so the more she said that the more it like freaked me out it's so it's like why is she saying she should be able to do it umm so words matter in terms of how it's specifically attended to”
- Bailey, LP patient

Difference as the "norm"

We developed an LP teaching module that featured 9 Standardized Patients of different body size, genders, ages, and skin colours in an attempt to demonstrate how different bodies require different considerations when performing a lumbar puncture.

Conclusion

• Patients need to be at the centre of health education and health care.
• By centring patient experiences and integrating diverse bodies, we are hoping to empower medical students to become more inclusive and effective doctors.

Introduction and purpose

• Few studies have explored sex differences in functional outcomes after ischemic stroke in young adults.
• The primary aim was to determine if functional outcomes among young adults with stroke differed based on sex.
• The secondary aim was to identify differences in stroke risk factors and etiologies between females and males.

Methods

• We conducted a retrospective analysis of consecutive acute ischemic stroke patients aged 18 to 55 years from a single centre stroke registry between 2018 to 2022.
• Using multivariable logistic regression, we analysed if modified Rankin Scale at 3-6 months (mRS, dichotomized 0-2 versus 3-6) was associated with sex.

Results

• We included 315 patients (127 female) with a median age of 48 years (IQR 42-52), median NIHSS of 10 (IQR 4-19) and median mRS (at 3-6 months) of 2 (IQR 1-3).
• Following adjustment for vascular risk factors, clinical stroke characteristics, baseline mRS, thrombolysis, stroke time metrics and unknown onset of symptoms, there was no significant difference in mRS (3-6 months) based on sex (p=0.40).

• Atrial fibrillation (p=0.01) and toxic drug use (p=0.001) were more frequent in males.
• Thrombolysis, thrombectomy and mortality rates were similar in both groups.

Conclusions

• Patient-oriented outcomes may be of interest in future studies as functional outcomes based on mRS do not differ between young male and female stroke patients.
• Males had a higher prevalence of risk factors including toxic drug use and atrial fibrillation.
• These findings could help develop targeted stroke prevention strategies in young adult stroke patients.

BACKGROUND

• Many patients feel they are not empowered to make independent medical decisions.¹
• Women have demonstrated difficulty discussing reproductive and pregnancy-related health choices with medical practitioners.²
• The development of decision aids have greatly empowered women in making their own medical decisions by facilitating collaborative decision making in obstetrics and gynecology.³
• Webtool-based decision aids have shown efficacy in promoting shared decision making and collaborative care in these groups, but are limited to family planning, prenatal screening, and cancer management.³
• No current decision aid in the literature exists to promote shared decision-making on pharmacological pregnancy-related care.

PURPOSE

• It allows the confluence of data sources, patients, and physicians to meet.
• It was developed over 2 years in collaboration between pharmacy and clinical neurology experts at the University of Waterloo and University of Toronto.

STUDY DESIGN AND METHODS

• A mixed-methods quality improvement study was used to collect patient feedback on the usability and appropriateness of a webtool focused on common issues faced by pregnant patients with chronic neurological conditions.

• Recruited participants were asked to rate the web tool according to the Systems Usability Score (SUS), Acceptability of Intervention Measure (AIM), and Intervention Appropriateness Measure (IAM).

RESULTS

Focus Group Thematic Results:

1. Suitability and usability of the tool depends on inherent user access to healthcare and geographic resources
2. Comprehension of webtool content is dependent on lived experience with the medical condition. 
3. User interface dictates how well users can comprehend the tool.

CONCLUSIONS AND FUTURE DIRECTIONS

• Our study demonstrates a proof of concept of a method of analysis that can be used for further refinement.
• No other similar framework currently exists within the current scope of the literature and highlights the need for future tools.
• Our study recruited patients from tertiary academic centres, further refinement of the tool would benefit from patient perspectives from more low-resourced areas.

• The presence of daytime impairments, such as reduced functioning, decreased energy, and/or fatigue, is one of the characteristics of insomnia disorder.¹
• An efficacious insomnia treatment ideally should improve subject-reported disease severity, as assessed by the Insomnia Severity Index (ISI), a 7-item self-reported questionnaire. Four of the 7 items specifically assess severity of daytime functional impairments.²
• Lemborexant (LEM) is a competitive dual orexin receptor antagonist approved in multiple countries for the treatment of adults with insomnia.^3,4
• In Study E2006-G000-303 (Study 303; SUNRISE-2; NCT02952820), the ISI total score, and items 4-7 for daytime function, led to larger and statistically significant (improvement) changes from baseline with LEM treatment compared with placebo (PBO) as assessed at 1, 3, and 6 months.⁵ 
  • ​​​​​​​Improvements with LEM treatment continued through 12 months.⁵

To assess the impact of LEM based on the level of severity of the daytime function items of the ISI in Study 303, this post-hoc analysis examined the impact of LEM compared with PBO on shifts in these items (improvements from very severe towards no problem) over 6 months, depending on baseline severity.

• Study 303 was a 12-month, phase 3, global, multicenter, randomized, PBO-controlled (for first 6 months), double-blind, 2-dose, parallel-group study in males and females (≥18 years of age) with insomnia disorder (Figure 1).⁶
• Additional details regarding study design, inclusion/exclusion criteria, the ISI (Table 1 - see full poster via QR code), and statistical analysis are included in the full poster.

Demographic Data

• Baseline demographic characteristics, including baseline ISI total score and DFS, were similar across treatment groups (Table 2).

Shifts in ISI Daytime Function Items

• 749 of 949 (78.9%) subjects completed the ISI both at baseline and at the end of Treatment Period 1: PBO, n=258/318 (81.1%); LEM5, n=257/316 (81.3%); LEM10, n=234/315 (74.3%).
• Shifts from baseline to Month 6 in total DFS between chosen ranges are shown in Table 3 (see full poster via QR code).
• The shift distributions, improvement from more severe daytime functioning impairment towards no daytime functioning impairment at 6 months, were overall significantly different, favoring both LEM5 (P<0.0001) and LEM10 (P=0.008) compared with PBO.
• A significantly greater proportion of subjects who reported severe-to-very severe problems in daytime functioning at baseline (DFS total score 13-16) showed improvement to lower rates of problems, compared with staying the same, at 6 months with LEM10 compared with PBO (Figure 2).
• A greater proportion of subjects who reported moderate-to-severe problems in daytime functioning at baseline (DFS total score 9-12) showed improvement to lower rates of problems, compared with worsening or staying the same, at 6 months with LEM5 compared with PBO (Figure 3).
• In subjects who reported only mild-to-moderate problems in daytime functioning at baseline (DFS total score 5-8), 39-48% across all treatments reported an improvement at 6 months (Figure 4).

Safety

• LEM was well tolerated; the majority of TEAEs were mild-to-moderate in severity (Table 4).

• More subjects treated with LEM for 6 months were able to improve their daytime functioning, regardless of baseline severity.
  • More LEM subjects’ scores moved into lower categories (eg, from reporting severe or very severe problems in daytime functioning to no or mild problems at 6 months) compared with those from subjects receiving PBO. 
• In subjects reporting moderate-to-severe or severe-to-very severe problems with daytime functioning at baseline (DFS scores 9-12 or 13-16), there was a notable improvement, with ~40-50% shifting to 0-4 (no or mild problem) at 6 months with LEM treatment compared with ~25-30% for PBO.
• When added to previous findings of improved daytime functioning sustained for 12 months, these data provide further evidence that LEM may be an appropriate treatment option for patients with insomnia who report severe impairments in daytime functioning in addition to their nighttime symptoms. 

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• Insomnia, characterized by problems falling asleep, staying asleep, and/or early awakening, is treated by hypnotic medications with distinct mechanisms of action.¹
• Many hypnotic drugs prescribed for insomnia are known to show abuse and/or dependence potential and a withdrawal syndrome; as such, some are classified under Schedule IV (CIV).^2,3
• The 3 dual orexin-receptor antagonists (DORAs; daridorexant, lemborexant [LEM], and suvorexant), members of the newest hypnotic class approved for the treatment of insomnia, were placed in CIV based largely on human abuse potential (HAP) studies,^4-8 but have fewer abuse-related events in the community, suggesting a potential overestimation of risk in the HAP studies.^9,10
  • This conclusion is based on several factors determined in the clinical development programs: Negative nonclinical studies, no off-target binding, low rates of abuse-related treatment-emergent adverse events (AEs) in clinical trials, and a paucity of on-line chat reports recommending DORAs to others for recreational purposes, among other factors.³
• At the time of their approval, there were insufficient postmarketing data from the community for consideration in the scheduling decisions. Currently, >8 years of postmarketing data are available across the 3 approved DORAs.

• To assess the abuse potential of DORAs, and other drugs used as hypnotics (benzodiazepines [BZs] and zolpidem [ZOL]), using real-world data from publicly available United States (US) and Japanese pharmacovigilance databases and an internal Eisai Global Postmarketing Safety Surveillance System.

Study Design and Data Sources

• This was an observational retrospective study that compared AEs, including abuse and withdrawal events, and other data such as mentions of misuse across 3 drug categories with distinct mechanisms of action frequently used in the treatment of sleep difficulties: DORAs (LEM, suvorexant, daridorexant), BZs (temazepam, triazolam, estazolam, brotizolam, etizolam, flunitrazepam), and ZOL.
• Data sources included the US FDA Adverse Event Reporting System (FAERS) database, Japan Adverse Drug Event Reporting (JADER) database, and Eisai's Global Postmarketing Safety Surveillance System (Table 1 - see full poster via QR code).
  • FAERS and JADER contain AE reports submitted by healthcare professionals, consumers, and product manufacturers.
• Additional details regarding study design are included in the full poster.

Analysis of FAERS

• Compared with BZs and ZOL, DORAs were associated with the lowest rates of: serious AEs (Table 2), suspected AEs of injury, poisoning, and procedural complications (as a percentage of total reports) (Figure 1), AEs (based on percentage of reports) of drug withdrawal syndrome (Figure 2A), drug abuse       (Figure 3A), and drug dependence (Figure 4A).

Analysis of JADER

• Compared with BZs and ZOL, DORAs were associated with the lowest rates of: AEs (based on percentage of reports) of drug withdrawal syndrome (Figure 2B), drug abuse (Figure 3B), and drug dependence (Figure 4B).

Analysis of Eisai Global Postmarketing Safety Surveillance System

• Since the time of LEM's marketing approval in 2020, there have been a small number of drug abuse, drug dependence, and drug withdrawal AEs reported to Eisai from the US, Canada, and Japan (Total number of reports, N=73) (Table 3 - see full poster via QR code).  
• Given the number of patients exposed postmarketing (~ 475 million patient days), and the number of reports (N=73), the calculated reporting rate corresponds to 
  ~ 0.15 cases per million patient days of global exposure.

• The findings from the FAERS and JADER databases suggest that DORAs have lower real-world abuse compared with BZs and ZOL. In accordance, data from the Eisai Global Postmarketing Safety Surveillance System database also reported low real-world abuse potential with LEM, a DORA.
• The current findings are consistent with low levels of abuse events with DORAs (eg, no reinforcing effects or a withdrawal syndrome) reported in nonclinical and clinical studies^3,23,24 and community-based reports from the FDA’s Controlled Substance Staff.^9,10 The findings suggest that relying exclusively on HAP studies for scheduling DORAs appears to overestimate their potential for abuse in the community and DORAs may not pose meaningful abuse potential and related risks.
• Providing clinicians with a means to differentiate between classes of hypnotics by re-evaluating the placement of DORAs in CIV appears warranted.

• Despite improved gender representation, women face gender-based barriers in academic medicine, especially in neurology^1,2
• In 2019, women accounted for only 36% of neurologists in Canada³
• Evidence suggests that gender disparity persists in the Canadian Institutes of Health Research (CIHR) funding⁴

Aim: To evaluate gender disparities in CIHR funding decisions for Canadian neurology divisions and departments
 

• Data on CIHR grant recipients, duration, quantity, and contribution within Canadian neurology divisions and departments (2008-2022) were collected from the CIHR Funding Decisions Database⁵
• Gender identity was determined by an application programming interface⁶
• Analyses conducted by Mann-Whitney U test and Glass rank biserial (r_g) correlation test

Outcomes:

1. Gender-based differences in CIHR grant prevalence, duration, and contribution amount within neurology
2. Subgroup analysis for Canadian licensed neurologists and Project Grant awards

• Of 1604 grants awarded, women received fewer grants (n=665, 42%), less funding by 2.5 times (p<0.0001), and shorter grant durations by 1.5 times (p<0.0001) annually than men
• Women were the minority of recipients (n=542; 45%) and less likely to be awarded grants (p<0.001) annually than men
• Differences were consistent in subgroup analyses 

• Gender disparities persist in CIHR funding: women receive fewer grants, lower contribution amounts, and are less likely to be recipients than men
• Current initiatives: GENDER R25 (NIH), Women Leading in Neurology program (AAN), women's neurology training and mentorship (University of Toronto)
• Future studies: trends over time, gender-diverse groups
• Future recommendations: gender-diverse reviewers, blind review, diversity training, public reporting of reviewer and recipient gender

References:

1. Tricco AC et al. CMAJ. 2021. PMID 33593950.
2. Nguyen AX et al. Front Neurol. 2021. PMID 34497579.
3. Canadian Medical Association. 2019. https://www.cma.ca/sites/default/files/2019-11/2019-06-spec-sex.pdf
4. Witteman HO et al. Lancet. 2019. PMID 30729688.
5. Canadian Institutes of Health Research. 2022. https://webapps.cihr-irsc.gc.ca/decisions/p/main.html?lang=en#sort=namesort%20asc&start=0&rows=20.
6. Gender API. 2022. https://gender-api.com/.

• Intracranial epidermoid cysts (IEC) are benign intracranial lesions
• Predominantly located in the cerebellopontine angle (CPA)¹
• 1% of intracranial tumors¹
• Rarely undergo malignant transformation^1,2

Aim: To report a case of IEC evolving into squamous cell carcinoma (SCC) 1-year post-resection and conduct a systematic review of cases of malignant transformations of IECs within 2 years.
 

• 11/2019: 48F presented with tinnitus and vertigo -> left CPA IEC on MRI
• 05/2022: Surgical resection, pathology confirmed IEC
• 07/2023: Presented with headaches, nausea, vomiting, right facial weakness, and rapid cyst progression -> cyst fenestration, pathology revealed high-grade SCC (p40+, p16-, Ki67 25-30%)
• 08/2023: Leptomeningeal involvement and enhancement of lumbar and sacral spine
• 09/2023: 26.7 Gy in 10 fractions of radiation
• 10/2023: Pembrolizumab + carboplatin x 4 cycles
• 05/2024: Continued on pembrolizumab alone

• 17 (8F, 9M) underwent malignant transformation of IEC within 2 years
• Mean age at presentation: 56.06 years
• Most in CPA (n=12, 71%); all transformed to SCC, of which 2 (12%) had LC

• Malignant transformations of IECs are rare
• We report a case of transformation within 1-year post-resection
• Regular follow-up is crucial for early malignancy detection and treatment
• Future studies should evaluate factors contributing to accelerated malignant progression of IECs

References:

1. Hamlat A et al. J Neurooncol. 2005. PMID 16193391
2. Vellutini EAS et al. Br J Neurosurg. 2014. PMID 24345076.

Acknowledgments: Thank you to the patient for providing informed consent to present this work.

• Sex and gender are distinct, non-interchangeable concepts with independent impacts on health outcomes in neurology.
• It is already known that women are under-represented in stroke and cognitive neurology research. 
• There is a growing number of pharmacologic options in neurology practice. In 2023, Neurology tied with Oncology and Hematology as specialties with the most new FDA drug approvals.
• The quality of sex and gender reporting and analysis in neurological randomized controlled trials (RCTs) remains unknown.

This poster aims to review RCTs leading to neurological drug approval by the FDA for their use of accurate sex and gender terminology and the incorporation of sex and gender into study design and discussion.

This is a cross-sectional review of peer-reviewed RCTs published between 1985 and 2023 and cited in the approval process of neurological drugs. Key steps were based on the PRISMA 2020 statement for systematic reviews and STROBE statement for reporting cross-sectional studies:

1. The Drugs@FDA database was screened by two independent reviewers and experienced third party to extract all agents approved for the treatment of a neurological disorder.
2. For each included drug, FDA drug labels and medical and statistical reviews were used to identify all trials cited in drug approval. Inclusion and exclusion criteria were applied to each trial.
3. Data were extracted from each included trial by two independent reviewers and third party conflict resolver. Extracted data included the use of sex and gender terms and their inclusion in data analysis, as well as trial characteristics.
4. Data were summarised using descriptive statistics. For continuous variables, the associations between study characteristics (e.g., publication year) and use of sex and/or gender terminology and inclusion of sex- and/or gender-based analysis were examined using logistic regression models. For binary characteristics, between-group differences were examined using Fisher exact tests.

Regarding study design:

• Sex- or gender-based analyses were undertaken in only a few studies (0-12%).
• Only 3 out of 216 studies mentioned sex- or gender-based analysis in their discussion sections. A further 5 studies discussed sex or gender as a limitation.

Regarding sex and gender terminology:

• Many studies (45.4%) did not use sex and gender terms rigorously.
• No studies included sex or gender minority group categories.
• Definitions of sex and gender were never provided.

Despite extensive research demonstrating the importance of sex-specific analyses and the obligation to consider sex as a biological variable for access to NIH funding since 2016, there has been no significant change (p>0.05) in the quality of reporting or analysis of sex or gender in therapeutic trials in neurology. Given the private funding model of most RCTs, drug approval-level requirements may be more effective to correct these shortcomings. 

• Ontario Stroke System operates on a hub-and-spoke model that centralizes acute stroke expertise at comprehensive stroke centres (CSC) which serve primary stroke centres (PSC) or non-designated centres (NDC)
• Code stroke activations involves rapid mobilization of health care resources
• The hyperacute stroke treatment window has recently been extended to at least 24 hours, leading to a surge in code strokes and out-of-protocol cases

1) Quantify the proportion of out-of-protocol code stroke activations in two large CSC in Toronto, Canada, and describe which criteria were not met
2) Compared use of thrombolysis or thrombectomy in those seen in- or out-of-criteria

Cohort

• Patients aged 18 years or older who were seen as code strokes in the ER between January 1, 2022 – December 31, 2022
• CSC1: St Michael’s Hospital (SMH) 
• CSC2: Sunnybrook Health Sciences Centre (SHSC) 
• Includes those arriving by paramedics (bypass protocol) and those activated by ER team 

Exclusions

• Inpatient code strokes
• Code strokes activated by another service
• Patients transfered from a PSC for thrombectomy

Data Collection

• Chart review was performed to determine if patients met FAST and ACT-FAST screening criteria
• Paramedic-activated strokes: data extracted from paramedic notes and stroke neurologist notes
• ER-activated strokes: data extracted based on the ER team’s notes/screening sheets (when available) and the stroke neurologist assessment.