Background: Phase 3 PREEMPT established safety and efficacy of 155-195U onabotulinumtoxinA in adults with chronic migraine (CM). This analysis of the PREDICT study (NCT02502123) evaluates real-world effectiveness and safety of 155U, 156-195U and 195U-onabotulinumtoxinA in CM. Methods: Patients received onabotulinumtoxinA approximately every 12-weeks (≤7 treatment cycles [Tx]) per Canadian product monograph). Primary endpoint was mean change from baseline in Migraine-Specific Quality of Life (MSQ) at Tx4. Headache days, physician and patient satisfaction were evaluated. Analysis stratified safety population (≥1 onabotulinumtoxin A dose) into 3 groups (155U,156-195U,195U) by dose received on ≥3 of the first 4 Tx. Results: 184 patients received ≥1 onabotulinumtoxin A dose (155U, n=68; 156-195U, n=156; 195U, n=13 on ≥3 Tx). Headache days decreased over time compared to baseline (Tx4: -7.1[6.7] 155U; -6.5[6.7] 156-195U; -11.2[6.4] 195U). Physicians rated most patients as improved, and majority of patients were satisfied at final visit (80.8% 155U; 83.6% 156-195U; 90% 195U). Treatment-emergent adverse events (TEAEs) were reported in 18/68(26.5%) patients in 155U-group, 41/65(63.1%) in 156-195U-group and 10/13(76.9%) in 195U-group; treatment-related TEAEs were 9(13.2%), 10(15.4%) and 3(23.1%) respectively; serious TEAEs were 0, 3(4.6%) and 1(7.7%), none treatment-related. Conclusions: Long-term treatment with 155U, 156-195U, and 195U-onabotulinumtoxinA in PREDICT was safe and effective CM treatment. No new safety signals were identified.

Background: There is no biological marker of progression in early Parkinson Disease (PD). Upper limb (UL) tremor is the most common motor symptom at onset. The significance of lower limb (LL) tremor remains unknown. We report on longitudinally followed autopsy-verified PD tremor onset cases. Methods: A chart review of longitudinally followed autopsy-verified PD cases was performed. Age and mode of onset were recorded at initial evaluation. Prognosis was measured by change in Hoehn and Yahr scale while on levodopa (LD). Results: Forty-nine patients were included. Thirty-eight cases had upper limb (UL), four lower limb (LL), and seven upper and lower limb (ULL) onset tremor. UL had 86.8% response to LD, LL 50% and ULL 85.7%. Sub-analysis of UL responders found 20% mild improvement, 53.3% moderate and 26.7% marked. ULL had moderate response in 83.3% and marked in 16.7%. LL responders only had mild improvement with LD. Conclusions: Tremor onset is most common in UL, followed by ULL and then LL. LL onset tremor cases have an inferior response to LD when compared to UL and ULL cases. We plan for further pathophysiologic studies to investigate LL onset in PD.

Background: Quantitative and objective neurophysiological assessment can help to define the predominant phenomenology and provide diagnoses with prognostic and therapeutic implications. We evaluated retrospectively the indications and final diagnoses of movement disorder neurophysiological evaluations in a specialized movement disorders centre. Methods: Reports from 2003 to 11/2021 were reviewed. The indications were classified according to predominant phenomenology, and the diagnosis of each study was categorized in subgroups of each phenomenology. Results: A total of 525 reports were evaluated. The mean age of patients was 51 years (range 5 – 89 years), and 50% were women. The most common indication was functional movement disorders (33%), followed by jerky movements (25%), tremor (20%), unsteadiness (6%), stiff person syndrome (4%), and other less common indications (12%). The most prevalent diagnoses were functional movement disorder (37%), followed by tremor (28%), comprising of essential (6%), dystonic (5%), cerebellar (4%), parkinsonian (3%) and other types of tremors (10%); and myoclonus (21%), including cortical (8%), subcortical (3%) and undefined (10%) types. Conclusions: This 17-year experience showed that neurophysiological testing can help in the diagnosis of movement disorders. More standardized techniques will encourage the widespread use of neurophysiology to evaluate movement disorders.

Background: Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system accompanied by chronic inflammation and neurodegeneration. An unmet clinical need in the management of MS is how to select an initial disease modifying therapy (DMT). Real-world evidence suggests that early aggressive control with high-efficacy medications results in better long-term prognosis. Methods: This retrospective study was conducted at Memorial University using Relapsing Remitting MS (RRMS) patients enrolled in the HITMS study. Analysis included study participants aged 18+ with RRMS and three years of clinical visits. Disability progression was measured by the Expanded Disability Status Scale (EDSS) and defined as a change of ≥ 1.0. Study subjects were categorized according to DMT at their initial visit. Results: In this cohort, 87 participants met the inclusion criteria; 67 were stable and 20 had disability progression. There was no significant difference in disability progression based on DMT regimen, and age, sex, and disease duration did not affect disability progression. Conclusions: Despite evidence that all RRMS patients go on a DMT, our cohort demonstrated a significant proportion remain DMT naive. Furthermore, the selection of DMT in this cohort appears to be appropriate, as there were no obvious differences in disability progression regardless of DMT.

Background: Approximately 25% of encephalitis cases in North America are immune mediated. For most forms of autoimmune encephalitis (AIE), risk of relapse is unclear and little evidence exists to guide which patients have the highest risk and whether standard treatments reduce this risk. Our objective was to determine the factors associated with AIE relapse. Methods: We performed a chart review consisting of 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 39/40 patients, 17/39 (44%) patients relapsed. Seropositive patients and those with abnormal CSF were more likely to relapse, although neither reached statistical significance (p=0.12, 0.059). Patients with longer duration of steroid and steroid sparing treatment prior to relapse, and those on steroids at the time of relapse, had milder relapses (p=0.024, 0.026, 0.047). There was no difference in steroid or steroid sparing treatment use at 3, 6, and 12 months between groups. Conclusions: Risk of relapse in AIE is high (44%), with most relapses occurring in the first 3 years. Continuous immunosuppression lessens the severity of relapse, although our study did not confirm it reduced the occurrence of relapse.

Background: New Canadian treatment optimization recommendations (TOR) were released in 2020 to guide clinicians on the optimal use of disease modifying treatments (DMTs). The alignment of current practices to TOR was investigated to identify potential areas for improvement in patient care. Methods: From January–July 2021, a chart audit of 160 patients was conducted by a sample of Canadian neurologists. Patient selection criteria included adult patients with relapsing-remitting MS, who had been switched from an initial DMT. Results: In alignment with TOR, most patients received a platform therapy initially (89%; n=143) and suboptimal efficacy response (MRI changes, relapses, disability progression) was the most common trigger for switching treatment. Furthermore, the expanded disability status scale was used in 94% (n=151) of cases during clinical assessment. In some instances, neurologists did not adhere to TOR. Only 10% (n=16) of patients were tested for cognitive function and over half (58%; n=93) did not receive gadolinium contrast at re-baseline MRI. Major criteria for switching therapies based on relapse rate, severity/recovery, or MRI were not followed in (n=4; n=27; n=7) patients respectively. Conclusions: Canadian neurologists are generally aligned with recent TOR for MS. However, they are not switching nearly as often or as early as per TOR criteria.

Background: There is growing body of evidence linking abnormal eye movements in people with multiple sclerosis (MS) to disease severity and cognition which could better detect disease progression. The objective of this study is to determine if a novel eye-tracking tool can accurately predict disease severity and cognitive status based on eye movement metrics and characterize how they evolve with progression. Methods: Persons with MS (n=132) will be followed over 4 years with clinical assessments every 6 months. Eye movements are also assessed while performing oculomotor tasks using Innodem Neurosciences’ patented eye-tracking technology. The eye movement metrics will be inputted into machine learning classifying algorithms to identify which metrics can serve as reliable Eye Movement Biomarkers (EMB) for MS progression and cognitive status. Results: There were 16 participants recruited as of January 2022 with mean age 47. 3 (SD 10.4; range 26-67), gender (12F/4M), EDSS 2.59 (SD 1.49; range 1.5-6.5), SDMT 51.4 (SD 14.1, range 24-78). With current enrollment, there is a negative correlation between EDSS and SDMT (r = -0.47) as observed in the literature. Conclusions: This trial will demonstrate the utility of EMBs for monitoring MS progression by improving physicians’ access to a reliable, non-invasive, sensitive and accessible marker of disease progression.

Background: Public health measures during the COVID-19 pandemic resulted in many multiple sclerosis (MS) patients being assessed virtually. Expanded Disability Status Scale (EDSS) scores, which are routinely obtained during MS consults, cannot be reliably calculated during virtual assessments. The Patient Determined Disease Steps (PDDS) is a validated patient-reported outcome measure of disability in MS. This study aimed to find real world evidence for the validity of PDDS as a surrogate of EDSS. Methods: Chart review of all MS patients from the MS Clinic in Saskatoon, Saskatchewan who completed PDDS forms emailed to them prior to their virtual visit (N = 277) was performed. 97 (35%) had documented EDSS scores prior to and following their self-reported PDDS. Correlational analysis between PDDS scores and pre and post EDSS scores was performed. Results: PDDS scores were highly correlated with EDSS scores before (r(95) = .79, p < .001) and after (r(95) = .84, p < .001) clinic closure occurred. Conclusions: This study provides real-world evidence that PDDS can accurately assess disability in MS when in-person assessments are not possible. Further investigation into patient demographics that increase the likelihood of completing PDDS assessments prior to appointments at our centre is ongoing.

Background: Although seizures are a well-recognized phenomena in patients with multiple sclerosis (MS) with many observational studies reporting its prevalence and incidence, the relative risk of seizures or epilepsy in adults with MS compared to those without is not well-described. Methods: We systematically searched MEDLINE and Embase, from their inception to January 1, 2022, using keywords and database-specific terms. We included observational studies that reported risk of seizures or epilepsy in adults with MS and that in a comparison group, consisting of people without MS or the general population. We used a random-effects meta-analysis to report a pooled adjusted risk ratio (RR) of seizures in adults with MS compared to the comparison group. Results: We screened 8,750 articles and included 17 studies, totaling over 192,850 adults with MS of which 6064 (3.1%) had seizures. Compared to a comparison group, the pooled adjusted RR of seizures in adults with MS was 2.86 (95% CI, 2.35-3.47, I2 = 95.8%). Conclusions: MS should be considered an independent risk factor for seizures or epilepsy. Further research should help identify patients with MS who are at risk of seizures, to improve screening and treatment and in turn reduce the burden of epilepsy in this population.

Background: Immunoglobulin supplies are limited; we aimed to determine if the COVID-19 pandemic was associated with difficulty accessing immunoglobulin treatment for patients diagnosed with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). Methods: A retrospective cross-sectional study was conducted with CIDP patients (n=16, 68.75% female, mean age 60.38 ± 11.32) recruited from three Montreal tertiary care institutions. Patients completed a questionnaire inquiring about changes in their immunoglobulin treatment during the pandemic and about their quality of life. We used weighted chi-squared statistical tests and Cramer’s V correlation ratios to measure associations with treatment change. Results: Eighteen months after the pandemic started, 25% of our population were receiving immunoglobulin treatment at a different frequency, 6.3% were receiving a different dose, 12.5% were receiving a different dose and frequency, and 6.3% were receiving a different treatment. Reasons associated with treatment change were worsening of neurological condition (18.8%; Cramer’s V=0.480; p-value=0.055), improvement of neurological condition (25%; Cramer’s V=0.577; p-value=0.021) and reduced availability of treatment (6.3%; Cramer’s V=0.258; p-value=0.302). There were no significant correlations between lower quality of life (p-value=0.323) or lower Rasch-built Overall Disability Scale score (p-value=0.574) and treatment change. Conclusions: Difficulty accessing immunoglobulin treatment was not significantly associated with treatment change for CIDP patients during the COVID-19 pandemic.

Background: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a neuroinflammatory disease mediated by antibodies targeting the GluN1 subunit of the NMDAR. It presents with well-defined neuropsychiatric symptoms, including psychosis, agitation, seizures, and memory disturbances. Movement disorders including orofacial dyskinesias are common, but often difficult to manage, with no specific published guidelines. Methods: A 23-year-old female was diagnosed with NMDAR encephalitis. She was treated with ovarian teratoma removal, corticosteroids, intravenous immunoglobulin therapy, rituximab, and tocilizumab. She continued to experience severe, self-mutilating orofacial dyskinesias. Tetrabenazine, haloperidol, and diazepam did not yield any sustained improvement. Tramadol was started based on a prior case report suggesting its efficacy. Results: Tramadol 50 mg po q6h led to immediate improvement in symptoms. Over the next 5 days, tramadol was increased to 150mg NG q6h and further reduced movements. When tramadol was held for one day, the movements significantly worsened and improved when it was restarted. Clonazepam 1mg NG QID also led to further improvement. Conclusions: Tramadol and clonazepam effectively treated severe orofacial dyskinesias in a patient with NMDAR encephalitis and refractory symptoms despite aggressive management. We propose early use of tramadol and clonazepam be considered for severe orofacial dyskinesias secondary to NMDAR encephalitis.

Background: MOG-IgG is associated with non-MS demyelinating disease of the optic nerves, spinal cord and brain. Specificity has been issue so we validated the live and fixed MOG-IgG CBAs against the Oxford Autoimmune Neurology Diagnostic Laboratory (OANG) live CBA as a comparator with high specificity. Methods: At BC Neuroimmunology lab (BCNI), 54 MOG-IgG serum samples previously positive by live-CBA at OANG and BCNI were blindly tested by commercial fixed CBA. All 54 MOG IgG positives came from MOG-IgG positive patients. In addition, 256 samples from healthy people and other neurolgic disease were tested. Results: The live MOG-IgG CBA performed at BCNI was 100% concordant (54/54) with OANG live CBA. In contrast, only 49/54 samples were found seropositive by the commercial fixed CBA. The BCNI live-CBA identified 3/256 control samples as positive while 6/256 controls were positive on the fixed commercial CBA. On this cohort the live CBA is 100% sensitive, 98.8% specific and has PPV of 95%. The commercial fixed MOG test is 91% sensitive, 97.6% specific and has PPV of 87.5%. Conclusions: BCNI live MOG-IgG CBAs are in 100% agreement with MOG-IgG. Three positive results in non-MOGAD associated clinical phenotype require further investigation. These data confirm the superiority of the live MOG CBA.

Background: Epilepsy mediated by immune cells must be identified early since immunotherapy has been associated with better clinical outcomes. This provides an overview of autoimmune TLE, emphasizing recent developments in its pathophysiology, imaging, and therapeutic interventions. Methods: Web-based research using advanced features of databases. Results: Epilepsy caused by immune dysfunction leads to inflammation of the brain. Inflammation play a role in the development of seizures. Proinflammatory molecules found to be overexpressed in neurons and glia of individuals with DRE, provoke a proinflammatory cytokines in the plasma and CSF. Autoimmune epilepsy is characterized by focal seizures refractory to ASMs accompanied by other neurological manifestations, as described by clinical scoring systems.Scoring systems are available to identify patients who are likely to be positive. The MRI findings include signal hyperintensities in the affected brain regions. EEG performed to exclude nonconvulsive seizures. Seizures resulting from autoimmune encephalitis are caused by antibodies to surface antigens and intracellular antigenes. Conclusions: Pathogenesis proposed to involve antibody-mediated ictogenesis. Immunotherapy is effective in autoimmune encephalitis with a positive prognosis if detected early. Limbic encephalitis has been shown to have a detrimental effect on cognition, mood, and behavior. Neuropsychology is an important outcome criterion for tracking disease progression and treatment success.

Background: Osmotic demyelination syndrome (ODS) is a known complication of rapid sodium correction. While the pons is classically the most vulnerable region to osmotic shifts, other structures may also be affected. Prognosis varies from death to full recovery, yet we cannot accurately predict a patient’s outcome in the acute phase. Methods: Patient chart, medical imaging, and laboratory findings were reviewed. Results: Here we present the case of a 57-year-old woman seen at our center, who was transferred from a community hospital in the context of ODS after having her serum sodium corrected from 106 mmol/L to 122 mmol/L within 24 hours. She showed depressed mental status, bulbar symptoms, ataxia and respiratory compromise, eventually requiring transfer to the intensive care unit for intubation. MRI of the brain showed striking demyelinating injury at the level of the pons. The patient was discharged to a rehabilitation facility, eventually achieving independence in activities of daily living. Conclusions: This case illustrates canonical neuroimaging findings associated with ODS. Despite extensive initial damage, long-term disability can be mitigated with appropriate care. Future studies seeking to identify specific markers imaging and clinical markers would be of interest to predict functional outcome.

Background: A single unprovoked seizure occurs in up to 10% of patients, but does not necessarily develop into epilepsy. It is unclear what determines the susceptibility to develop epilepsy. Although brain network changes have been ascertained in people with epilepsy, this field has not been studied in single seizure patients. Methods: Using 7T resting-state fMRI scanning, and co-registration watching a movie for naturalistic analysis of functional connectivity (Fc). Whole brain, Fc and Brodmann areas were analyzed using phase similarity measures and graph theory. Results: Ten patients with a single unprovoked seizure and fourteen age-and sex-matched healthy controls were recruited. Baseline characteristics were similar. Fc at baseline had no differences between groups. Movie-driven analysis did not show a significant difference overall regions but we observed significant differences in default mode and Visual association cortex as well as Dorsal posterior cingulate cortex (Dorsal PCC). Conclusions: Although no network connectivity differences were found between patients and controls, when movie-driven data was analyzed, differences were seen when comparing patients in the default mode network, visual association cortex, and dorsal posterior cingulate.

Background: This is a population-based retrospective study of cardiac and neurological complications of COVID-19 among Ontario Chinese and South Asians. Methods: From January 1, 2020 to September 30, 2020 using the last name algorithm to identify Ontario Chinese and South Asians who were tested positive by PCR for COVID-19, their demographics, cardiac, and neurological complications including hospitalization and emergency visit rates were analyzed compared to the general population. Results: Chinese (N = 1,186) with COVID-19 were found to be older (mean age 50.7 years) compared to the general population (N = 42,547) (mean age 47.6 years) (p < 0.001), while South Asians (N = 3,459) were younger (age of 42.1 years) (p < 0.001). For neurological complications, the 30-day crude rate for Chinese was 160/10,000 (p < 0.001); South Asians was 40/10,000 (p = 0.526), and general population was 48/10,000. The 30-day all-cause mortality rate was significantly higher for Chinese at 8.1% vs 5.0% for the general population (p < 0.001), while it was lower in South Asians at 2.1% (p < 0.001). Conclusions: Chinese and South Asians in Ontario with COVID-19 during the first wave of the pandemic were found to have a significant difference in their demographics, cardiac, and neurological outcomes.

Background: This study aimed to evaluate chronic pain and fatigue in COVID-19 patients after 12 months of hospitalization. Methods: We studied the COVID-19 patients discharged from Hospital, between March 10 to April 20, 2020. Results: A total of 157 patients were included in this study. Forty-three patients (27.4%) complained of chronic fatigue and muscle weakness in the last six months. The visual analog fatigue scale (VAFS) score of 3.84 ± 1.48 was obtained. Forty patients (25.5%) were suspected of Chronic Fatigue Syndrome (CFS). Twenty-four patients (15.3%) had severe chronic pain or exacerbation of previous chronic pain, most of which were reported in the lower back (70.8%) and lower extremities (66.7%). Pain intensity had a mean score of 2.33 ± 0.87 and was mainly described as “muscle cramps,” “persistent dull pain,” and “boring and numbing.” In women, chronic pain and fatigue, extended hospital stays, ICU admission, and depressed mood were common than in men. For these pain and fatigue, 37% used nonsteroidal anti-inflammatory drugs, and 16.3% used antidepressants. Only one person had applied for physiotherapy, and none of the patients had received psychotherapy Conclusions: Fatigue and chronic pain in patients recovering from COVID-19 are common complications, even after 12 months of illness.

Background: Measuring outcomes that matter to patients is a key component of ensuring patient-centred care. In Chronic Inflammatory Neuropathies (CINs), where immunomodulatory treatments have risks and high costs, systematic evaluation of disease progression is needed to ensure patients are achieving outcomes that reflect their values and goals. The aim of this project is to evaluate the feasibility of objective outcome measure (OOM) use in the clinical setting. Methods: Prospective data was collected from 27 participants with CIDP or MMN. Participants completed and provided feedback on patient-reported outcome measures including quality of life, activity and participation, pain and fatigue, as well as grip strength, 9-hole peg test, 10 meter walk, muscle strength and sensation. Focus groups were conducted to collect qualitative data. Results: The majority of OOMs were considered relevant to 90% of participants. The top three ranked measures were muscle strength testing, daily activities questionnaire and quality of life questionnaire. 52% of participants identified balance and/or detailed gait assessment as an important factor that was not part of collected OOMs. Conclusions: OOMs allow for appropriate monitoring of patients and optimization of immunotherapy treatment. By tracking longitudinal results that matter to patients, patients can better participate in shared-decision making. Clinicians should adopt OOMs going forward.

Background: Wild-type transthyretin amyloidosis (wtATTR) is an important cause of infiltrative cardiomyopathy in older adults. Carpal tunnel syndrome (CTS) is one of the most common extra-cardiac manifestations of wtATTR; however, the prevalence, severity, and risk of recurrence following carpal tunnel release (CTR) remain poorly understood. Methods: This retrospective cohort study reports findings from a single-centre experience of routine neurological screening of newly diagnosed wtATTR patients including nerve conduction studies. Consecutive wtATTR patients between 2014 and 2021 were included. Results: Seventy-nine wtATTR patients were included, 73 (92%) males, mean age of 79 years. Seventy-four (94%) had median neuropathy at the wrist (MNW), 50% having a prior diagnosis with the remaining 50% being diagnosed at screening. The majority with MNW were symptomatic (53, 67%) with moderate or severe disease (66, 84%) bilaterally (42, 53%) on electrophysiologic testing. Nineteen (24%) had recurrent CTS despite previous CTR. At the time of screening, 19 (24%) were prescribed wrist splinting and 36 (46%) were referred for CTR. Conclusions: Carpal tunnel syndrome is common in wtATTR. Most have bilateral disease with moderate to severe MNW at the time of wtATTR diagnosis. Recurrence of CTS after CTR is more common in wtATTR patients than in the general population.

Background: Mutations in the Cu/Zn superoxide dismutase 1 (SOD 1) gene are estimated to cause 20% of familial ALS and 1-2% of sporadic cases. Accurate gene variant classification of novel mutations in amyotrophic lateral sclerosis (ALS) has deepened our understanding of clinical phenotypes, provided pathologic insights, and is crucial to incorporating emerging therapies. Methods: We describe a case of a 75-year-old female who presented with a rapidly progressive lower motor neuron syndrome leading to flaccid quadriparesis and complete loss of independence over a five month period. Results: Genetic testing demonstrated a heterozygous variant of uncertain significance in the SOD1 gene with a g > c point mutation at position 382 that has been described in one other patient in available literature. MR of the lumbar spine demonstrated abnormal smooth nerve root enhancement. Conclusions: This novel mutation in the SOD1 gene may be associated with a rapidly progressive phenotype of sporadic ALS. Ventral nerve root enhancement should not exclude a diagnosis of ALS especially in the absence of nodularity or nerve enlargement.