Background: Climate change, and fossil fuel combustion threaten the health of children globally through direct and indirect mechanisms,1 such as the exacerbation of ambient air pollution.1,2 Increased ambient air pollutant concentrations are associated with emergency department (ED) visits for episodic and paroxysmal neurologic conditions in adults in the Toronto region of Canada.4,5 We hypothesize that, in Calgary, Alberta, increased ambient air pollutants will be positively associated with the daily burden of pediatric ED presentations for migraine and seizures, and that a greater effect size may be present due to increased regional variability in ambient PM2.5 concentrations.3,4 Methods: Emergency records from the National Ambulatory Care Reporting System, comprising 17552 primary seizure and headache cases between 0-18 years of age and presenting to Calgary-region emergency departments between January 2012-December 2021, will be included. Quasi-Poisson regression modeling incorporating ambient air pollutants, seasonality and meteorological covariates will estimate relative risk and 95% confidence intervals of ED visit counts relative to increases in air pollutants. Results: Results currently pending and will be available for presentation. Conclusions: Significant results may inform further inquiry into the impact of air pollutants on children with neurological conditions and identify potential contributions of air quality to healthcare service demand in the Calgary region.

Background: Trofinetide significantly improved core symptoms of Rett syndrome (RTT) with an acceptable safety profile in LAVENDER. Here, we report the safety and efficacy results of LILAC and LILAC-2, open-label extension studies of LAVENDER. Methods: Females with RTT, aged 5–21 years, received twice-daily, oral trofinetide in LILAC for 40 weeks. Participants who completed LAVENDER and LILAC continued trofinetide in LILAC-2, a 32-month extension study. Safety assessments included the incidence of adverse events (AEs). Efficacy endpoints included the Rett Syndrome Behaviour Questionnaire (RSBQ) and the Clinical Global Impression–Improvement (CGI-I) scale. Results: Overall, 154 patients were enrolled in LILAC. The most common AEs were diarrhea (74.7%) and vomiting (28.6%). The mean (standard error [SE]) change from the LAVENDER baseline to Week 40 in the LILAC study in RSBQ was -7.3 (1.62) and -7.0 (1.61) for participants treated with trofinetide and placebo in LAVENDER, respectively. Mean (SE) CGI-I scores compared with the LILAC baseline at Week 40 were 3.1 (0.11) and 3.2 (0.14) for patients treated with trofinetide and placebo in LAVENDER, respectively. Similar safety and efficacy trends were observed in LILAC-2. Conclusions: Trofinetide continued to improve symptoms of RTT in LILAC and LILAC-2 with a safety profile consistent with LAVENDER.

Background: Wernicke encephalopathy (WE) is a neurological emergency defined by acute encephalopathy, oculomotor dysfunction, and ataxia. Pediatric cases of WE are underdiagnosed despite having a similar incidence to adults. There are no available treatment guidelines for pediatric WE. Prompt treatment with thiamine can prevent devastating consequences. Methods: A rapid review of the literature of the past 20 years with selected relevant older articles was conducted for the research question “How does child and adolescent thiamine therapy management for Wernicke Encephalopathy compare to adult guidelines?” All articles reporting the investigation, management and treatment of Wernicke encephalopathy – both non alcohol related and alcohol-related pediatric cases – were included. Articles not reporting clinical outcomes were excluded. Results: Eleven case studies including one available review article, met the inclusion and exclusion criteria. An algorithm was created for the organization of published reports of the management of WE for children and adolescents. Key considerations were included for the prevention, identification, acute and ongoing management of patients with WE. Conclusions: The recognition of risk factors for thiamine deficiency and symptoms of acute WE should prompt immediate treatment with thiamine – as a routine and safe therapy in the pediatric population.

Background: Neurodegeneration with Brain Iron Accumulation (NBIA) is a heterogenous group of disorders with the common theme of iron accumulation in the basal ganglia. These disorders typically present in childhood with progressive neurodegeneration and neuropsychiatric symptoms. Caring for an individual with NBIAs is intensive, however it is unknown what factors impact caregiver well-being and quality of life. Methods: Common themes were obtained via literature review of quality of life surveys in children with neurological and chronic illnesses. Five domains were addressed: Diagnosis, Communication, Symptom Management, Clinical Experience and Resources/Support. The survey was approved by the Family Advisory Committee at the CHEO Research Institute and the CHEO REB. The survey was distributed via the Rare Connect Platform to Canadian caregivers. Results: Survey responses are being analyzed and will be presented at the CNSF. Within each domain, Likert scales will be analyzed. Domains will be ranked according to the caregiver responses. Conclusions: Results of this survey will assist in developing care management guidelines, resources for families and help with future advocacy for patients and families affected by NBIAs. The results will also help guide future NBIA Canada Family Conferences.

Background: Intracranial hemorrhage (ICH) in newborns poses a significant challenge to wellbeing and development. In preterm neonates, germinal matrix hemorrhage is most common. In term neonates, prevalence and type of ICH has not been well elucidated. This systematic review aims to assess prevalence, type, and risk factors of ICH in term neonates. Methods: A systematic review was conducted. Inclusion criteria was ICH in neonates born at 37+ weeks gestation. Exclusion criteria was one type of ICH, one risk factor, sample size <20, text not in English, full text not accessible. Eligible studies were evaluated by two authors, data was extracted and analyzed using a predesigned template and MetaXL. Results: A total of 1226 records were initially identified and 20 studies were included in the final analysis. The overall prevalence of ICH was 9.3%. This was subdivided into an asymptomatic subgroup (5.8%) and symptomatic subgroup (29.3%). Analysis showed CT detected ICH most commonly. Extra-axial hemorrhage was most commonly detected (~30%), with subdural more common than extradural hemorrhages. The odds of having an ICH was significantly higher with instrumental delivery (3.75%). Conclusions: This shows that prevalence of ICH is relatively high in symptomatic children. Measured prevalence varies according to the type of modality used for screening.

Background: Cortical myoclonus originates at cerebral cortex, predominantly occurring on voluntary movements. Few case reports described usage of Acetazolamide (ACZ) for myoclonus. Methods: Chart review of 2 patients was performed. Literature review was conducted on myoclonus and ACZ using Pubmed. Results: 22-year-old female was diagnosed with Progressive Myoclonic Epilepsy (PME) secondary to a KCNC1 mutation. Her symptoms started at 10 years old with bilateral tonic clonic seizures (BTCS), later developing progressive ataxia and myoclonus, involving face and limbs, which worsened with stimulus and menses. Medications included Perampanel, Clonazepam and Levetiracetam, however myoclonus was still limiting. At the age of 19, ACZ 250 mg BID was started for 2 weeks around her menses. Follow up revealed significant improvement of myoclonus, resulting in better ambulation, balance and speech, sustained 2.5 years after. 67-year-old male presented BTCS at the age of 53 along with cortical myoclonus, dementia and ataxia, leading to diagnosis of PME with a mutation on IRF2BPL. Improvement of myoclonus occurred with ACZ 250 mg BID biweekly, although balance and cognition still deteriorated. Conclusions: Previous literature outlines 4 cases of action myoclonus that responded to ACZ. We believe that ACZ should be considered to treat myoclonus, especially in cases with cortical involvement and hormonal fluctuations.

Background: Sleep-wake states (SWS) affect the expression of interictal epileptiform discharges (“spikes”), which affects resultant source localization calculations used in epilepsy evaluation. We hypothesize that spike localizations from non-REM sleep 1-3 are most concordant with one another. Methods: We used Standardized low-resolution brain electromagnetic tomography (sLORETA) in Curry 8 software to calculate source localization voxels of spikes in N1-3, REM, or wakefulness (W). We assessed voxel concordance between N1-N2-N3/N1-N2-W/N1-N3-W/N2-N3-W/REM-N1-N2/REM-N1-N3/REM-N2-N3/REM-N1-W/REM-N2-W/REM-N3-W. We classified concordances into those containing and not containing a SWS (e.g. N1 vs. not-N1 = N1-N2-N3/N1-N2-W/N1-N3-W/REM-N1-N2/REM-N1-N3/REM-N1-W vs. REM-N2-W/REM-N3-W/REM-N2-N3/N2-N3-W) for comparison. Results: Concordances did not differ for N1-3 or W. However, concordances with REM were lower than those without REM as a fraction of source localization space (median 32.1% vs. 56.1%, p<0.001) and cortical grey matter (median 20.4% vs. 27.3%, p=0.003). Conclusions: As expected, source localizations from spikes in N1, N2, and N3 did not significantly differ from one another because these three states are constituent members of non-REM sleep. Surprisingly, however, source localizations derived from awake spikes – not a constituent of non-REM sleep – also did not differ. In contrast, REM was most different by reproducibly exhibiting the least three-way concordance. These findings reinforce the unique localizing ability of REM sleep.

Background: Electrophysiological tests such as the tapping test are used to distinguish functional and organic tremors, in which patients with functional tremor commonly show entrainment and amplitude reduction (>50% decrease relative to baseline) of contralateral tremor during tapping. While these features are suggested to be specific to functional tremor, the tapping test in Parkinson’s disease (PD) tremor has not been tested. Methods: We evaluated 18 PD patients (2F, age 64.17±7.30 [mean±SD] years) with rest and postural tremors using surface electromyography and triaxial accelerometry. Patients were recorded while tapping at 1, 3 and 5 Hz with the contralateral arm at rest or outstretched. Tremor amplitude and frequency were calculated using power spectrum analysis from accelerometer recordings. Results: Reduction of rest tremor amplitude was observed in 3/18 patients during 1 and 3 Hz tapping. Reduction was seen in 3/16 and 1/16 patients with postural tremors at 1 and 3 Hz tapping, respectively. Frequency shifts (>1.5 Hz) were observed in 3/18 rest tremors and 6/16 postural tremors. Seven patients exhibited rest and/or postural tremor entrainment during 3 or 5 Hz tapping. Conclusions: Distractibility and entrainment can be found in PD tremor. The tapping test may not reliably distinguish between PD tremor and functional tremor.

Background: We evaluated the utility of the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) in predicting risk of gastrostomy tube (G-tube) insertion in patients with ALS. Methods: We conducted a retrospective study using the Pooled Resource Open-Access ALS Clinical Trials Database. People with ALS, at least two ALSFRS scores, and baseline swallowing subscore >1 were included. G-tube outcome was defined as reaching a swallowing subscore ≤1. Predictors were ALSFRS bulbar subscores (swallowing, speech, salivation). Survival analyses estimated median time to outcome and cumulative probability of outcome within 91 days. Individuals were censored at last ALSFRS score. Results: We included 6,943 participants. Median [95% CI] time to G-tube insertion was 245 [228, 285], 562 [547, 621], and 1,268 [980, 1,926] for baseline swallowing subscores of 2, 3, and 4, respectively. Probability of G-tube insertion was associated with baseline swallowing, speech, and salivation subscores (log-rank test p < 0.0001). For patients who transitioned to a swallowing subscore of 2 or 3, 18.1% [95% CI 16.1, 20.3] and 1.9% [95% CI 1.3, 2.7] required G-tube insertion within 91 days of score transition. Conclusions: ALSFRS bulbar subscores may identify patients at risk of G-tube insertion. Probability of G-tube insertion within 91 days is low if swallowing subscore ≥3.

Background: Treatment of generalized myasthenia gravis (gMG) with reduced steroid dosages may minimize steroid-associated AEs. Corticosteroid dosage changes were not permitted during the 26-week, CHAMPION MG study of ravulizumab in adults with anti-acetylcholine receptor antibody-positive (AChRAb+) gMG. Participants who completed the study could receive ravulizumab in the open-label extension (OLE; NCT03920293); corticosteroid adjustments were permitted. Methods: Patients could receive intravenous ravulizumab (blind induction or bridging dose at Week 26 [OLE start] for those previously receiving placebo or ravulizumab, respectively, then 3000–3600 mg at Week 28 and every 8 weeks thereafter) for ≤4 years. Results: Among 161 patients (78 ravulizumab, 83 placebo) who entered the OLE and received ravulizumab for ≤164 weeks, 113 received oral or enteral corticosteroids during the OLE; the proportion treated with >10 mg/day corticosteroids decreased from 58% (n=66) at first OLE dose to 37% (n=42) (35 [31%] received ≤5 mg/day and 71 [63%] received ≤10 mg/day) at last reported dose. Fourteen patients (12%) discontinued corticosteroids. The mean (SD) corticosteroid dosage/patient decreased from 17.5 (11.9) mg/day at first OLE dose to 11.7 (10.9) mg/day at last assessment. Conclusions: Ravulizumab decreased corticosteroid use in patients with AChRAb+ gMG, suggesting a steroid-sparing role for ravulizumab.

Background: Zilucoplan, a macrocyclic peptide complement component 5 inhibitor, sustained efficacy for up to 60 weeks of treatment, with a favourable safety profile in patients with acetylcholine receptor autoantibody-positive generalised myasthenia gravis in an interim analysis of RAISE-XT (NCT04225871). We evaluate the safety and efficacy of zilucoplan up to 96 weeks. Methods: RAISE-XT, a Phase 3, multicentre, open-label extension study, included patients who participated in the double-blind Phase 2 (NCT03315130) and Phase 3 (NCT04115293) zilucoplan studies. Patients self-administered daily subcutaneous zilucoplan 0.3mg/kg injections. Primary outcome was incidence of treatment-emergent adverse events (TEAEs). Secondary outcomes included change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) score. Results: At data cut-off (11 May 2023), median (range) exposure to zilucoplan was 1.8 (0.11–5.1) years (N=200). TEAEs occurred in 191 (95.5%) patients; the most common TEAE was COVID-19 (n=64; 32.0%). At Week 96, mean (standard error) change in MG-ADL score from double-blind study baseline was –6.33 (0.49) and –7.83 (0.60) for patients who received zilucoplan 0.3mg/kg and placebo in the double-blind studies, respectively. Conclusions: Zilucoplan demonstrated a favourable long-term safety profile. Efficacy was sustained for 96 weeks in patients who had previously received zilucoplan and who switched from placebo.

Background: In the Phase 3 RAISE study (NCT04115293), zilucoplan significantly improved MG-specific outcomes in patients with acetylcholine receptor autoantibody-positive generalised MG. After the first 12 weeks of the open-label extension study, RAISE-XT (NCT04225871), corticosteroid dose could be changed per the investigator’s discretion. We evaluate changes in corticosteroid dose during treatment with zilucoplan in RAISE-XT. Methods: In RAISE-XT, adults who completed the Phase 2 or RAISE studies (N=200) self-administered daily subcutaneous zilucoplan 0.3mg/kg, either continuing with zilucoplan or switching from placebo. Primary outcome was incidence of treatment-emergent adverse events (TEAEs). We assessed (post-hoc) the proportion of patients who discontinued/reduced or increased corticosteroid dose relative to double-blind baseline up to Week 60. Results: At Week 60, 30% (n=18/60) and 22% (n=12/54) of patients receiving corticosteroids in the zilucoplan and placebo-switch groups, respectively, reduced/discontinued corticosteroids (mean dose reductions: 14mg and 16mg; mean [SD] CFB in MG-ADL scores: -5.00 [3.96] and -5.67 [6.89]. 12% (n=7/60) and 7% (n=4/54) of patients in the zilucoplan and placebo-switch groups, respectively, increased corticosteroid dose (~12mg mean increase in both groups). TEAEs occurred in 188 (94.0%) patients (data cut-off: 08 September 2022). Conclusions: While receiving zilucoplan, discontinuation or dose reduction in concomitant corticosteroids was possible with maintained efficacy.

Background: Reducing oral corticosteroids (OCS) use can alleviate the risk of many adverse events related to long-term OCS use. Here, we evaluate real-world utilization of OCS among patients with generalized myasthenia gravis (gMG) over the first 6 months following efgartigimod initiation. Methods: Patients with gMG using OCS who initiated efgartigimod treatment were identified retrospectively from an open US medical and pharmacy claims database (IQVIA Longitudinal Access and Adjudication Data [LAAD], April 2016-April 2023). Average daily dose (ADD) of OCS was analyzed during the 3-month period preceding efgartigimod initiation, and at 3 and 6 months post-efgartigimod initiation. Results: Of 231 patients assessed, 17 (7.4%), 109 (47.1%), and 105 (45.5%) had baseline OCS ADD of 0–5 mg, 5–20 mg, or >20 mg, respectively. At 3 and 6 months post-efgartigimod, 82 (35%) and 99 (43%) patients, respectively, reduced ADD by ≥5 mg. Proportion of patients with ADD of 0–5 mg increased >3-fold (7% baseline vs. 26% 6 months post-efgartigimod) and proportion of patients with ADD of >20 mg decreased by 35% (45% baseline vs. 29% 6 months post-efgartigimod) following efgartigimod initiation. Conclusions: Approximately 43% of patients were able to decrease steroid use or achieved steroid-free status within 6 months of efgartigimod treatment initiation.

Background: A key efficacy indicator in generalized myasthenia gravis (gMG) treatment is improvement in MG-ADL score. Minimal symptom expression (MSE, MG-ADL total score of 0 or 1) is explored as a novel proposed treatment target in gMG in the phase 3 study of intravenous efgartigimod, ADAPT, and its open-label extension, ADAPT+. Methods: Post hoc analyses of acetylcholine receptor antibody positive participants in ADAPT (n=129) and ADAPT+ (n=111) were performed. Results: In ADAPT, 44.6% receiving efgartigimod achieved MSE vs 10.9% of participants given placebo. Despite less frequent assessment during ADAPT+, 40.5% of participants achieved MSE. Eighty-one percent of participants treated with efgartigimod who achieved MSE in ADAPT also achieved MSE during ADAPT+; 23% who had not achieved MSE in ADAPT did in ADAPT+. Achieving MSE was associated with substantial improvements in QMG, MGC, MG-QoL15r, and EQ-5D-5L mean scores of 11.4, 16.0, 12.4, and 0.3 points, respectively, from baseline to best score (across all visits). These drastic improvements resulted in quality of life (QoL) comparable to that of healthy populations. MSE achievement also resulted in sustained improvements in these disease-specific and QoL measures. Conclusions: Participants who achieved MSE showed substantial and consistent improvements across multiple disease measures and experienced QoL comparable to that of healthy populations.

Background: LC-FAOD may be missed in neuromuscular (NM) clinics due to its rarity and absence from common NM genetic panels. The Canadian Neuromuscular Disease Registry (CNDR) collects real-world patient data and includes a network of clinician-investigators. Our objective was to inform future registry work by evaluating diagnosis pathways for LC-FAOD patients and estimating the number followed at Canadian NM clinics. Methods: A questionnaire was developed with an expert committee and circulated to 111 CNDR-affiliated NM neurologists. Results: 12 neurologists in 5 provinces, primarily adult-treating (n=8) completed the survey (10.8% response rate). Eleven (91.7%) practiced for >10 years. Agreement trends existed between definition of, and tests to evaluate, rhabdomyolysis. Four clinics routinely follow LC-FAOD patients. In the last 1-2 years, respondents diagnosed approximately 91 patients with LC-FAOD (mean=7.5 per clinic). 83.3% never received continuing education on LC-FAOD, though 75% indicated interest in expert-led webinars. Further data will be presented. Conclusions: Low sample size limits conclusions about LC-FAOD clinical trends. Results suggest LC-FAOD may be under-diagnosed or not routinely followed by NM specialists, limiting viability of an LC-FAOD registry. Practitioners may be interested in LC-FAOD-specific education. Future work could include collaboration with metabolic geneticists on education initiatives to raise awareness and improve care for these patients.

Background: Carpal tunnel syndrome (CTS) is less common in children but can be associated with significant disability. Pediatric CTS can be associated with an underlying disorder most commonly storage disorders including mucopolysaccharidoses (MPS). We report a patient with bilateral severe CTS secondary to Weill-Marchesani Syndrome (WMS). Methods: A retrospective chart review was completed. Results: A five-year-old female presented with a three-year history of bilateral thumb weakness and insensate digits two and three. Nerve conduction studies (NCS) revealed severe bilateral CTS. She underwent bilateral carpal tunnel release (CTR). Unfortunately, post-operative NCS was unchanged. Ultrasound showed significant median nerve compression with flexor tendon thickening. Metabolic investigations showed no evidence of a storage disorder. Trio whole exome sequencing showed two de novo likely pathogenic variants in ADAMTS10: c.1174delC, p.H392TfsX9 and a deletion of exons 3-8. Her exam was also noted to show bilateral camptodactyly and brachydactyly, and bilateral cataracts characteristic of WMS. Conclusions: Identifying the etiology of CTS is important for management and prognosis. WMS is a genetic connective tissue disorder that can cause brachydactyly and abnormal tendon thickening, which can have implications on surgical outcomes. Awareness of this diagnosis prior to surgery would allow for better patient counseling and management decisions.

Background: The use of patient reported and functional outcome measures in routine practice enhances shared decision making and supports patient-centred care. This study compared the perspectives of Chronic Inflammatory Neuropathy (CIN) patients and providers regarding their experience using an outcome measure panel. Methods: A one year study was conducted to evaluate a nine measure outcome set in routine clinical practice for CIN. The panel included patient-reported outcome measures (e.g., I-RODS and EQ-5D-5L) and functional measures (e.g., grip strength). At the conclusion of the study, participants and providers completed an online questionnaire on their experience. Results: 25 patients and five providers completed the questionnaire. Both patients and providers reported benefit in tracking disease progression, supporting treatment-related decisions, and broadening views of health. Both groups agreed patient involvement in care was enhanced. Preference for specific measures, frequency, and data presentation differed. Providers emphasized integration into electronic medical records and streamlining processes. 100% of providers and 80% of patients wanted to continue completing outcome measures. Conclusions: CIN patients and providers recognize the value of integrating outcome measures into routine care. To effectively implement these measures in clinical settings, it is important to understand the patient and provider perspective and prevent unnecessary burdens to ensure sustainability of use.

Background: Charcot Marie Tooth disease is a polygenic disorder with cannonical features of distal amyotrophy, acrohypesthesia, and tight tendoachilles of either axonal (type 2) or demeylinating (type 1) varieties. Type 1 CMT patients are required to possess conduction slowing of a sufficient degree to qualify as demyelinating. Presented is a middle-aged man with an unremarkable neurologic exam and normal electrophysiology. Methods: Standard electrophysiological techniques were employed to obtain the nerve conduction data (Natus Nicolet EDX AT2; Middleton, WI, USA). Repeated next generation sequencing and deletion/duplication analyses were performed. Results: The nerve conduction studies showed no evidence of demyelination in the upper or lower extremeties. The duplication error was confirmed with repeat testing. The heterozygous PMP22 gene duplication encompassed the entire coding sequence involving exons 1-5. Conclusions: CMT1A accounts for the vast majority of dysmyelinating hereditary neuropathies. Phenotypic variability is well described. Presentations include (a) classic conduction slowing, (b) intermediate slowing, (c) conduction block, (d) HNPP-like, (e) absent CMAPs, and (f) normal NCSs in young infants. This is the first case of a neurologically intact adult with CMT1A. Cryptogenic genetic modifier-effect(s) are posited as a possible explanation of the lack of penetrance. Identifying the nature of this modification may prove instructive for future therapies.

Background: Chronic inflammatory demyelinating polyradiculoneuropathies (CIDP) is a rare, acquired polyneuropathy, especially in children, affecting the peripheral nervous system. It most commonly presents in a symmetric, proximal and distal, sensorimotor fashion. Immunosuppression and immunomanipulation are treatment modalities. We present a case of a 14 year old male with severe progressive CIDP who became refractory to steroid and IVIg but responded to Rituximab. Methods: Case presentation: A 14-year-old male with a history of asymmetric quadriparesis was diagnosed with CIDP. He had an initial partial response to IVIG and prednisone but then rapidly became refractory to even weekly IVIG and prednisone. Rituximab was therefore started. Results: Within 12 weeks his strength improved from quadriplegia to walker-assisted gait. By 22 weeks he achieved independent ambulation. His JAMAR hand grip increased from 0 to 28 kg. His worst recordable median conduction velocity (CV) improved from a nadir (MRC 0/5) of 14% of normal to 52% at full recovery (MRC 5/5). Conclusions: This case highlights several important clinical points. Dramatic improvement is possible in cases of quadriplegic CIDP. Strength recovery is not linearly related to CV recovery. There appears to be a role for polytherapy.

Background: Late onset Pompe disease (LOPD), rare autosomal recessive lysosomal storage disease, resulting from mutation in alpha glucosidase enzyme (GAA) can present even in 6th decade of life. Slowly progressive, subtle, limb girdle pattern of weakness (LGPW), with auxiliary features such as ptosis, enlarged tongue, axial rigidity, facial diplegia, variable degree of respiratory weakness is not uncommon. Hypertrophic and electrical cardiac abnormalities are well described in LOPD. Methods: We present a case of 67-year-old male presenting with proximal weakness, subtle ptosis, bilateral quadriceps and shoulder girdle atrophy, and left toe numbness. PMHx: CABG, NSTEMI. Statin use. FMHx: noncontributory. Results: EMG: L5 radiculopathy, with unexpected myopathic units in hip/pelvic/ shoulder girdle muscles with active denervation and muscle irritability. CK, CRP, SPEP, ANA, LFTs, HMG-CoA reductase: normal. GAA enzymatic activity=0.96µmol/L/hr (low), genetics: pathogenic variants in GAA gene: c.-32-13T>G and c.1194+3G>C. ECHO: severe diastolic dysfunction, restrictive left ventricular filling. PFTs: normal. Diagnosed with LOPD, started on therapy. Conclusions: LOPD remains a differential for LGPW especially in older patient population with history of cardiopulmonary features. Age-appropriate conconminant pathologies may confound the diagnostic process.Symptoms may preceed diagnosis for years.GAA enzymatic activity followed by genetic testing remains readily available and can confirm diagnosis, preventing delay of approved therapy.