Background: Care partners of people with Parkinson’s disease (PD) must continually cope with various stressors due to changes resulting from the disease process, including assisting and supporting with their medical, emotional, and social needs. Caregivers’ expectations, preferences, and experiences on PD management are a cornerstone to guarantee a comprehensive treatment of the disease and may be influenced or determined by cultural backgrounds. Methods: Comprehensive literature review to investigate the roles, experiences, and needs of caregivers of PwPD across cultures. We critically reviewed and analyzed the all published studies that examined the impact of cultural diversity on caregiving in PD. Results: Among some significant results, we found profound differences in caregivers’ experiences and perceptions between U.S, Mexican, and Latin-American, Asian, African and Indian caregivers. There are clear negative reinforced effects between caregiver status, education, health, labor participation and income-generating capacity, and social protection combined with the age and gender differences. Canadian information was not available. Conclusions: There is still a gap in the literature with a need for social and health services to understand the cultural factors that impact caregiver burden in PD to facilitate wellbeing and support from health and social services to better aid those in the caregiver role.

Background: Pain in a common symptom in adult-onset idiopathic dystonia (AOID). An appropriate tool to understand this symptom is needed to improve AOID patients’ care. We developed a rating instrument for pain in AOID and validated it in cervical dystonia (CD). Methods: Development and validation of the Pain in Dystonia Scale (PIDS) in three phases: 1. International experts and participants generated and evaluated the preliminary items for content validity; 2. The PIDS was drafted and revised, followed by cognitive interviews to ensure suitability for self-administration; and 3. the clinimetric properties of the final PIDS were assessed in 85 participants. Results: PIDS evaluates pain severity (by body part), functional impact and external modulating factors. It showed high test-retest reliability the total score (0.9, p<0.001), intraclass correlation coefficients higher than 0.7 for all items and high internal consistency (Cronbach’s alpha 0.9). Convergent validity analysis revealed a strong correlation between the PIDS severity score and the TWSTRS pain subscale (0.8, p<0.001), the brief pain inventory short form (0.7, p<0.001) and impact of pain on daily functioning (0.7, p<0.001). Conclusions: The PIDS is the first specific questionnaire developed to evaluate pain in patients with AOID with high-level clinimetric properties in people with CD.

Background: Pain is one of the most bothersome symptoms reported in Parkinson’s disease (PD), yet its underlying pathophysiological mechanisms are not well understood. Its prevalence and effects on quality of life in patients with monogenic forms of PD have not been systematically explored. Methods: Comprehensive literature review exploring the association between monogenic forms of PD (SNCA, PRKN, PINK1, DJ1, and LRRK2) and pain. We included pain in ATP13A2, VPS35, and GBA1 mutation carriers. After initial screening, sixty-five relevant articles were identified. Studies’ design, sample sizes, and pain outcome measures were highly heterogeneous. Results: Our review suggests that patients with some PD monogenic causes show a higher prevalence of specific pain subtypes. While painful foot dystonia is more frequently reported in SNCA and PRKN carriers, the last ones also describe frequent lower back pain mostly. Pain in general is most commonly reported in PINK1 mutation carriers followed by patients with LRRK2 mutations. Pain as an initial symptom and severe symptom is well described in GBA1-PD patients. There is limited and insufficient evidence to report on pain and ATP13A2, DJ1, and VPS35 mutations. Conclusions: Linking genetic profiles to pain outcomes may have a meaningful clinical impact, facilitating individualized treatment for pain in PD.

Background: Dopa-responsive dystonia (DRD) is a rare disorder with a classic presentation of childhood or adolescent-onset dystonia. This is characterized by parkinsonism, diurnal fluctuations, and a dramatic response to low doses of levodopa. It has been reported that female carriers of the genetic mutation are more often affected than males. Methods: A 62-year-old man with DRD. He is a sibling of the first documented case of DRD with autopsy. Results: He noticed mild clumsiness at 10 years old when he would fall playing games. He gave up playing hockey in his 30s because of his balance. Neurological exam at age 49 revealed mild findings of parkinsonism and dystonia of the right leg. He was started on levodopa/carbidopa 100/25 mg 1/2 pill BID with significant and sustained improvement and resumed playing hockey. His sister had onset at age 5 with walking on tiptoes with obvious dystonia when examined at age 8; she was well controlled for many years on straight levodopa (without decarboxylase inhibitor) at a dose of 250mg TID. Conclusions: These cases of siblings with DRD exemplify varying degrees of severity among family members and genders with the same condition. Genetic results are pending and will be presented.

Background: Cognitive impairment is a common manifestation of anti-LGI1 encephalitis and is typically defined as prominent memory deficits. We frequently encounter frontal cognitive-behavioural deficits when evaluating these patients, but this has yet to be well described in the literature. Methods: Patients with anti-LGI1 encephalitis were retrospectively identified from three tertiary centres in Toronto, Ontario between 2013 and 2022. Their medical records were evaluated and frontal features were categorized based on diagnostic criteria for behavioural variant frontotemporal dementia (bvFTD). Results: Nineteen patients were identified (median age 60 years [range 18–84]; 10 [52.6%] male). Eighteen (94.7%) had frontal cognitive-behavioural symptoms. Two developed these symptoms during treatment with steroids and were excluded from further analysis. The remaining 16 presented with behavioural disinhibition (n=13), apathy or inertia (n=6), perseverative, stereotyped or compulsive/ritualistic behaviours (n=6), hyperorality and dietary changes (n=4), a neuropsychological profile with predominant deficits in executive tasks (n=4), and loss of sympathy or empathy (n=4). Nine (47.3%) met diagnostic criteria for possible bvFTD. Anterograde memory impairment was common (n=14). Of the 16 patients with frontal features, 6 had faciobrachial dystonic seizures. Conclusions: Patients with anti-LGI1 encephalitis exhibit frontal cognitive-behavioural symptoms in addition to memory impairment. Clinicians should consider anti-LGI1 encephalitis in the differential diagnosis of bvFTD.

Background: Approximately 25% of encephalitis cases in North America are autoimmune (AIE). For most forms of AIE, it is unclear which patients have the highest relapse risk and whether standard treatments reduce this risk. Our objective was to determine the overall risk of relapse and whether chronic immunosuppressive therapy modifies that risk. Methods: We performed a chart review consisting of all patients with AIE presenting to the Calgary Neuro-Immunology Clinic and Tom Baker Cancer Centre between 2015 and 2020. Predictors of relapse were determined with use of t-test. Results: Outcome data was assessable in 39 patients, 17/39 (44%) patients relapsed, and most relapses (76%) occurred within 3 years. Patients not on any immunosuppression at the time of relapse had a greater increase in CASE score, a proxy for presentation severity, at relapse compared to those on immunosuppression (p=0.0035). Conclusions: The risk of relapse in AIE is high (44%). Immunosuppression at the time of relapse, which may occur up to 3 years after initial presentation, lessens the relapse severity, although it remains unclear if it can reliably prevent relapses. Our data enforces the importance of long-term follow up and that ongoing immunosuppression may be helpful, particularly in the first 3 years after initial presentation.

Background: Autoantibody testing for suspected autoimmune encephalitis (AIE) in Alberta is commonly performed by Mitogen Dx (MDx) using cell-based assays (CBAs) for cell surface antibodies and line immunoassay (LA) for intracellular antibodies without confirmatory tissue immunofluorescence/immunohistochemistry (TIFF/IHC). Duplicate testing is often sent to Mayo Clinic (MC) verify, resulting in increased costs. Methods: Antibody panel results were obtained for all patients who had testing sent to both MC and MDx from adult hospitals in Calgary between 2018 and 2020. Positive antibodies were evaluated to be pathogenic/non-pathogenic by chart review and expert consensus. Results: Thirty-four individuals had antibody panels completed at both labs. Overall agreement (positive/negative panel) was fair (κ = 0.24, p =.08), even after excluding low-titre GAD65 antibodies through MC (n=9, 26.5%). MDx reported more non-pathogenic serum results, including: anti-SOX1 (n=3), anti-NMDAR (n=2) and anti-GABA(B)R (n=1). All pathogenic antibodies (n=3) were positive in both laboratories. Conclusions: No new pathogenic antibodies were identified by sending duplicate testing to MC; however, a larger number of non-pathogenic antibodies were reported by MDx, likely due to lack of confirmatory TIFF/IHC. Antibody testing for AIE should be done in labs performing confirmatory TIFF/IHC on all CBA/LA results to avoid unnecessary investigations and/or treatments.

Background: Patient-centred care is important in the management of chronic inflammatory neuropathies (CIN) given the heterogeneity in disease course and treatment response. Patient Reported Outcome Measures (PROMs) support value-based healthcare by aligning treatment goals with what matters most to patients. This study evaluated the relevance of PROMs to patients and the feasibility of use in clinical management. Methods: PROMs assessing quality of life, pain, fatigue, and overall disability were collected prospectively from 32 patients with CIN every three months over a 12-month period. Patients provided feedback on relevance of the measures. PROMs were sent electronically prior to the visit. Results: Completion rate was 92%. Home vs. in-clinic completion increased from 56% to 85% over the course of the study. There was an association between completion of the panel and perceived relevance. The PROMs were consistently rated as highly relevant, with disability and fatigue measures rated highest. Conclusions: PROMs are appraised as highly relevant among patients with CIDP and MMN. Patients require support initially but adapt to electronically delivered home completion of questionnaires. We recommend inclusion of PROMs into routine clinical practice as a means of capturing aspects of health that are not easily assessed in a clinic visit.

Background: Antibody panels are one diagnostic tool within the comprehensive evaluation of suspected autoimmune encephalitis (AIE). Over-reliance on antibody panels contributes to misdiagnosis and inflated healthcare costs. Methods: Inpatients or outpatients who had AIE antibody testing ordered from one of four adult hospitals in Calgary between January 2018 – January 2020 were included. Medical records of 150 individuals were reviewed, including those with positive antibodies or testing sent to Mayo Clinic, plus a random sample. Results: AIE antibody panels were sent for 469 individuals during the 2-year period; 42 were positive (9.0%) of which 10 were pathogenic. Of 150 individuals included in chart review, 27 (18.0%) met criteria for possible AIE at presentation and 16 (10.8%) met criteria for definite AIE at final diagnosis. Overall, antibody testing was ordered in both serum and CSF in 36.3% (versus 69.2% meeting possible AIE criteria); MRI brain was performed in 92.7% (possible AIE 92.6%), EEG in 78.7% (possible AIE 100.0%), and lumbar puncture in 66.7% (possible AIE 96.3%). A sizable proportion did not receive malignancy screening (overall 48.7%; possible AIE 29.6%). Conclusions: Antibody panels are overemphasized in the assessment for AIE and often performed unnecessarily, while other recommended clinical tests are not consistently completed.

Background: Burst suppression (BS) is an EEG pattern in which there are isoelectric periods interspersed with bursts of cortical activity. Targeting BS through anesthetic administration is used as a tool in the neuro-ICU but its relationship with cerebral blood flow (CBF) and cerebral autoregulation (CA) is unclear. We performed a systematic review investigating the effect of BS on CBF and CA in animals and humans. Methods: We searched MEDLINE, BIOSIS, EMBASE, SCOPUS, and Cochrane library from inception to July 2022. The data that were collected included study population, methods to induce and measure BS, and the effect on CBF and CA. Results: In total 45 animal and 26 human studies were included in the final review. In almost all the studies, BS was induced using an anaesthetic. In most of the animal and human studies, BS was associated with a decrease in CBF and cerebral metabolism, even if the mean arterial pressure remained constant. The effect on CA during periods of stress (hypercapnia, hypothermia, etc.) was variable. Conclusions: BS is associated with a reduction in cerebral metabolic demand and CBF, which may explain its usefulness in patients with brain injury. More evidence is needed to elucidate the connection between BS and CA.

Background: This project aims to bridge the gap between clinical data being collected at a local hospital to be used for research. Methods: 1.5T high-resolution anatomical MRI scans were collected from ten participants who were already undergoing clinical, imaging, and neurological assessment as part of their standard-of-care. Additional statistical models were used to examine the relationship between grey matter (using voxel-based morphometry [VBM]) and scores on the Toronto Cognitive Assessment (TorCA). Results: There was a lack of consistency in MRI scanning protocols and inconsistent reporting of clinical and neuropsychological data across participants. No significant relationship was found using the p-corrected images at p < 0.05. When viewing uncorrected images at a threshold of p < 0.001, we found a significant positive correlation between TorCA scores in the areas of the bilateral superior frontal gyrus, frontal pole, brain stem, and left putamen. Conclusions: Although no significant relationship was found between VBM metrics and TorCA scores, this project represents a crucial step in connecting health research with clinical practice where neuroimaging and neuropsychological assessments are already being collected. This project also informed our research team of areas that are needing to be streamlined and operationalized in future strategies for data collection and input.

Background: This is a population-based retrospective study of neurologic and cardiac complications of COVID-19 among Chinese and South Asians in Ontario during waves 1-3. Methods: Chinese and South Asians with COVID-19 were identified using a validated surname algorithm and their outcomes of mortality, and cardiac and neurologic complications with those of the general population using multivariable logistic regression models. Results: Compared to the general population (n= 439,977), the Chinese population (n= 15,208) was older (mean age 44.2 vs 40.6 years, P < 0.001) and the South Asian population (n= 46,333) was younger (39.2 years, P < 0.001). The Chinese population had a higher 30-day mortality (odds ratio [OR] 1.44; 1.28-1.61) and more hospitalization or emergency department visits(OR 1.14; 1.09-1.28), with a trend toward a higher incidence of cardiac complications (OR 1.03; 0.87-1.12) and neurologiccomplications (OR 1.23; 0.96-1.58). South Asians had a lower 30-day mortality (OR 0.88; 0.78-0.98) but a higher incidence of hospitalization or emergency department visits (OR 1.17; 1.14-1.20) with a trend toward a lower incidence of cardiac complications(OR 0.76; 0.67-0.87) and neurologic complications (OR 0.89; 0.73-1.09). Conclusions: Ethnicity continues to be an important determinant of mortality, cardiac and neurologic outcomes, and healthcare use among Ontario patients with COVID-19.

Background: Efgartigimod is a human IgG1 antibody Fc-fragment that reduces IgG levels through FcRn blockade. A key efficacy indicator in the treatment of IgG autoantibody-mediated generalized myasthenia gravis (gMG) is improvement in MG-ADL score. Methods: The ADAPT phase 3 trial evaluated safety and efficacy of efgartigimod in patients with gMG, including reaching and maintaining of minimal symptom expression (MSE; defined as an MG-ADL total score of 0 or 1). Results: 167 patients (AChR-Ab+, n=129; AChR-Ab-, n=38) were randomized to receive treatment cycles of 4 weekly infusions of efgartigimod or placebo. Significantly more AChR-Ab+ efgartigimod-treated patients achieved MSE during cycle 1 compared to placebo-treated patients (40.0% [n=26/65] vs 11.1% [n=7/63; P<0.0001]). In cycle 2, 31.4% (n=16/51) of AChR-Ab+ patients in the efgartigimod cohort achieved MSE compared to none in the placebo cohort. MG-ADL score improved by ≥6 points in 56.9% of AChR-Ab+ efgartigimod-treated patients compared to 20.6% of placebo-treated patients in cycle 1. Most patients achieved MSE by week 4 of a cycle, paralleling early reduction in IgG levels, and MSE duration ranged from 1 to ≥10 weeks. Adverse events were predominantly mild to moderate. Conclusions: Efgartigimod treatment resulted in more patients with AChR-Ab+ gMG achieving both MSE and clinically meaningful MG-ADL improvements.

Background: Several case series describe patients with refractory acetylcholine receptor antibody-positive (AChR) myasthenia gravis (MG) treated with hematopoietic stem cell transplant (HSCT). In this report, we describe four patients with anti-muscle-specific kinase (MuSK)MG treated with HSCT. Methods: We reviewed the records of all patients undergoing HSCT for MG in the Alberta Blood and Bone Marrow Transplant Program and identified 4 patients with anti-MuSK MG. Results: All 4 patients had severe disease (Myasthenia Gravis Foundation of America score IVb-V) and were refractory to multiple treatments, including rituximab. 3 patients improved with no clinical manifestations or mild symptoms and remained as such for 2, 3.5, and 5.5 years. In these 3 patients, adverse events ranged from treatable infections and transient dyspnea to persistent fatigue and premature menopause. The average worst Myasthenia Gravis Activities of Daily Living (MG-ADL) scores improved from 14.7 before to 0.3 after HSCT while their mean worst Myasthenia Gravis Quality of Life Questionnaire (MG-QoL15) scores improved from 26.7 to 0. The fourth patient developed pneumonia and passed away from respiratory failure 8 weeks post-transplant. Conclusions: In patients with severe refractory anti-MuSK MG, it may be reasonable to consider HSCT but with an appreciation of the associated risks.

Background: Females with generalized myasthenia gravis (gMG) report lower quality of life (QoL) compared to males. Our objective was to determine whether sex differences in treatment and time to treatment initiation may contribute to this difference. Methods: We performed a single centre retrospective study of people diagnosed with gMG. We used multivariable logistic and Cox regression models to assess the association between sex and study outcomes, adjusting for duration from onset to diagnosis, age at diagnosis, thymoma, and antibody status. Results: 179 people with gMG were included. Mean age at diagnosis was 58.4 years, mean follow-up was 4.8 years, and 58.1% were male. There was no association between sex and odds of starting prednisone (adjusted odds ratio [aOR]=0.58, 95% confidence interval [95%CI]=0.28-1.19, p=0.14) or steroid sparing agents (aOR=0.72, 95%CI=0.39-1.35, p=0.31). Similarly, sex was not associated with time to starting prednisone (adjusted hazard ratio [aHR]=0.74, 95% confidence interval [95%CI]=0.52-1.06, p=0.10) or steroid sparing agents (aHR=0.82, 95%CI=0.55-1.22, p=0.33). Females were more likely to start plasmapheresis (aOR=3.15, 95%CI=1.09-9.07, p=0.03). Conclusions: We found no sex differences in first and second line immunotherapy for gMG that might explain differences in QoL. Females were more likely to initiate plasmapheresis, which may reflect greater disease severity.

Background: IgG4 autoantibodies to neurofascin-155 (NF-155) have been described in a subset of patients with chronic inflammatory demyelinating polyneuropathy (CIDP). While reports suggest an acute onset is more likely than in antibody negative CIDP, little literature exists around the subsequent course of NF-155 positive cases that originally presented with an acute inflammatory demyelinating polyneuropathy (AIDP) phenotype. Methods: Two male patients, ages 51 and 59, presented with similar, <2 week histories of lower extremity weakness. Patients were diagnosed with AIDP and treated with IVIG. Following initial improvement, both patients relapsed. One patient was treated with IVIG and steroids with subsequent improvement; however, he was unable to be weaned from steroids without experiencing recurrence of symptoms. The other patient was not retreated. Testing for NF-155 IgG was sent. Results: The first patient ultimately required Rituximab for stable improvement, the other improved spontaneously. Both patients later had positive tests for NF-155 IgG4 antibodies. Conclusions: Both of our NF-155 positive cases had initial AIDP-like presentations, followed by a relapsing course and excellent eventual recovery. This result, along with limited other available cases, suggest that in patients with an AIDP-like presentation, NF-155 IgG4 autoantibodies could be a marker of disease recurrence, but do not necessarily predict a poor outcome.

Background: There is a well-established association between idiopathic inflammatory myopathies (IIM) and malignancy. There are no evidence-based guidelines amongst neurologists and rheumatologists on the choice and timing of malignancy investigations. Our aim is to characterize the current gaps and uncertainties amongst neurologists and rheumatologists with malignancy screening in IIM patients. Methods: An online survey consisting of 18 multiple-choice questions related to IIM malignancy screening was distributed to adult neurologists and rheumatologists in Canada. Quantitative and descriptive analysis was performed. Results: The majority of respondents (96%, n=68) performed malignancy screening. There was variability in practice including delegation and choice of screening tests, influence of patient-specific factors, and time and length of repeat testing. Only 18% of respondents were confident in their malignancy screening practices. Between neurologists and rheumatologists, there were differences in the number of IIM patients seen, consideration of patient-specific factors and choice of screening investigations. Further details and data will be presented at the conference. Conclusions: There is a lack of consensus and confidence in the choice and timing of malignancy investigations in IIM, with neurologists and rheumatologists differing in their approaches. Further research is required to better understand the relationship between IIM and malignancy to create expert-led consensus guidelines.

Background: The Neuromuscular Disease Network for Canada (NMD4C) aims to improve the care of Canadians with neuromuscular diseases. It has identified a need to support clinicians in implementing clinical guidelines with the use of checklists for initial evaluation and clinical follow-ups. The objective of the study was to develop a pragmatic management checklist to support clinical guidelines for diagnosis and follow-up of myotonic dystrophy type 1 (DM1). Methods: A practice-based DM1 checklist will be reviewed by a panel of 35 experts using an online survey. The survey has been drafted using the Appraisal of Guidelines Research and Evaluation tool for assessing Recommendation Excellence (AGREE-REX). The experts will rate: (1) the quality of each checklist recommendation, and (2) the applicability of each recommendation based on their clinical setting. Scores will be compiled and discussed among experts to achieve consensus. Results: The compiled checklist items were organized into three sections: (1) initial evaluation, (2) follow-up visit and (3) general treatment recommendations. Feedback from experts across Canada, results on feasibility, and a finalized checklist will be presented. Conclusions: The development of a feasible treatment checklist is a useful KT tool that DM1 experts across Canada could apply in their own clinical settings.

Background: The 26-week double-blind, randomized, placebo-controlled period (RCP) of the CHAMPION MG study (NCT03920293) demonstrated ravulizumab’s efficacy and tolerability in anti-acetylcholine receptor antibody-positive (AChR Ab+) generalized myasthenia gravis (gMG). Methods: In the ongoing open-label extension (OLE), patients receive intravenous ravulizumab (blind loading dose in placebo-treated patients or bridging dose in ravulizumab-treated patients, then 3000–3600 mg according to body weight every 8 weeks) for ≤4 years. Data from RCP baseline up to Week 60 were analyzed. Results: Ravulizumab’s long-term efficacy (n=161) and safety (n=169) were assessed. Patients who switched from placebo in the RCP to ravulizumab in the OLE (n=83) showed rapid improvement (least squares mean, 95%CI) in Myasthenia Gravis-Activity of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) total scores, which were maintained through 34 weeks (MG-ADL: −1.7, −2.7 to −0.8; QMG: −3.1, −4.2 to −1.9). Improvements achieved by ravulizumab-treated patients (n=78) in the RCP were sustained through 60 weeks (MG-ADL: −4.0, −4.8 to −3.1; QMG: −4.1, −5.4 to −2.9). Ravulizumab was well tolerated; no meningococcal infections were reported. Four deaths unrelated to study treatment occurred. Conclusions: Ravulizumab demonstrated sustained improvements in MG symptoms and was well tolerated for up to 60 weeks in adults with AChR Ab+ gMG.

Background: Guillain Barre Syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are the two most common forms of treatable IMNs. Antibodies targeting proteins at paranodal cell-adhesion molecules such as contactin-1 (CNTN1), neurofascin-155 (NF155), contactin-associated protein 1 (CASPR1), and nodal neurofascins-NF140 and NF186, have been discovered in CIDP patients. Methods: Between August 2021 and January 2023, at BC Neuroimmunology laboratory, Vancouver we screened a total of 214 sera of patients for detecting nodal and paranodal antibodies with a fixed CBA. These patient sera were assayed for the presence of NF140, NF155, NF186, CNTN1, plus Caspr1 antibodies. The final diagnosis and response to therapy of positive cases were evaluated by a questionnaire requested from their physicians. Results: 10 cases were positive for nodal/paranodal antibodies by CBA (mean age 52.4 ± 15.4 years). Two cases were NF155 Ab positive CIDP with good response to conventional therapies. Three cases were double positive for NF140 and 186 Abs, three were double positive for CNTN1 and CASPR1 Abs. Interestingly, two cases were triple positive with GBS presentation. Conclusions: We identified a subgroup of nine patients with CIDP nodal and paranodal antibodies. Among them, two cases had triple positive antibodies with GBS presentation and poor response to plasma exchange and IVIg.