American Neurological Association Research Articles

RETRACTION: Mechanism of ARPP21 antagonistic intron miR-128 on neurological function repair after stroke.

Chai, Z., Zheng, P., Zheng, J. (2021) Mechanism of ARPP21 antagonistic intron miR-128 on neurological function repair after stroke. Annals of Clinical and Translational Neurology, 8: 1408-1421. https://doi.org/10.1002/acn3.51379 The above article, published online on 28 May 2021 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief Ahmet Hoke and Wiley Periodicals LLC on behalf of the American Neurological Association. The retraction has been agreed following a report by a third party who found that images in Figure 6 of the above article had been published previously in the following articles by other authors: Zhao etal. 2019 (1) and Shao etal. (2). Additionally, images from Figure 4B in the above article had been previously published by other authors in Zhao etal. 2020 (3). The authors did not respond to an inquiry by the publisher and requests to supply original data and images. Because the authors did not provide an explanation or original data for review, the data reported in this article is considered unreliable and the journal must issue a retraction. The authors did not respond to our notice of retraction.

Retraction: 5-Lipoxygenase gene transfer worsens memory, amyloid, and tau brain pathologies in a mouse model of alzheimer disease.

Retraction: Jin Chu, Phillip F. Giannopoulos, Carolina Ceballos-Diaz, Todd E. Golde, Domenico Pratico (2012), 5-Lipoxygenase gene transfer worsens memory, amyloid, and tau brain pathologies in a mouse model of alzheimer disease. Ann Neurol., 72: 442-454. https://doi.org/10.1002/ana.23642 The above article, published online on 09 May 2012 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor-in-Chief, Kenneth L. Tyler, American Neurological Association and Wiley Periodicals LLC. After concerns about data manipulation were raised, a thorough review of figures 2D, 6A, 6C and 7B by the authors revealed some inappropriate duplication. Given the extent of the identified issues, the authors (Dr. Pratico and Dr. Golde) have lost confidence in the original data, and asked to retract the article since the conclusions can no longer be considered valid. The co-authors, Jin Chu, Phillip F. Giannopoulos and Carolina Ceballos-Diaz were unavailable for comment.

Demographics, Practice Analysis, and Geographic Distribution of Neuro-Ophthalmologists in the United States in 2023

To assess the demographic characteristics and geographic distribution of neuro-ophthalmologists practicing in the US. A cross-sectional study. Neuro-ophthalmologists across the US. In this cross-sectional study, public databases from the American Academy of Ophthalmology, North American Neuro-ophthalmology Society, American Neurological Association, and American Academy of Neurology were used to identify neuro-ophthalmologists in the US as of April 2023. Providers' office locations were geocoded using ArcGIS pro, version 2.9 (Esri). Data on age, sex, and residency and fellowship training were collected. Analysis was performed using SPSS 28.0 (IBM Corp, Armonk, NY). Neuro-ophthalmologists' demographics, and information about their medical education, post-graduate education, residency training, fellowship training, years in practice, practice environment, and geographic distribution of neuro-ophthalmologists across US. A total of 635 neuro-ophthalmologists (436 male, 68.7%) were identified. The strong majority (599, 94.3%) graduated from an allopathic medical school. Most of the 85 physicians who held a secondary graduate degree had a PhD (54, 63.5%). Although nearly three-quarters (429, 67.6%) completed their residency in ophthalmology, 159 (25%) did residency in neurology and 47 (7.4%) in both. Nearly one-third (191, 30.0%) were trained in more than one fellowship, including oculoplastic (78, 12.3%) or pediatric ophthalmology (53, 8.3%). The average post-fellowship years of experience was 23.8 ±13.7 years, with 134 (21.1%) in their early career (< 10 years), 120 (18.9%) in their mid-careers (10 - 19 years), and 381 (60.0%) in their late careers (> 20 years). Male neuro-ophthalmologists had 10.5 ± 1.1 more years of experience than females (p < 0.001). Three states (Maine, South Dakota, Wyoming) and 2897 counties (93.2%) had no neuro-ophthalmologists. Counties without a neuro-ophthalmologist had lower median income (p < 0.001), lower access to a vehicle (p = 0.024), and lower rates of health insurance (p = 0.012). Practicing neuro-ophthalmologists are mostly male and are often trained in more than one subspecialty. More than half of the practicing neuro-ophthalmologists are in their late careers, which may further exacerbate the existing geographic and socioeconomic disparities in access to neuro-ophthalmology.

Poster (Clinical/Best Practice Implementation) ID 1969157

Background This study examined the effects of concomitant TBI on injury epidemiology, management and outcomes of individuals with traumatic SCI. Methods A propensity-score matched cohort study compared a SCI+TBI group (n=1018) with a SCI-only group (n=3687), which were matched on a 1:1 ratio by age, sex, severity and level of SCI, and Charlson Comorbidity Index. TBI was defined as a Glasgow coma score of &amp;lt;15 at admission. Both groups were compared regarding injury epidemiology (mechanism, ethnicity, GCS, other injuries), management (mechanical ventilation, traction, Methylprednisone, surgery, time to decompression), and post-SCI outcomes (length of stay [LOS], International Standards for Neurological Classification of SCI [ISNCSCI] motor subscore, Functional Independence Measure, discharge destination, spasticity and pain at discharge). Results Overall, being white (OR=5.332, p=0.0265) was associated with having TBI, while having other body injuries (OR=0.095, p=0.0065) was associated with the SCI-only group. Odds of dying in a hospital were 2.442 times larger for the TBI+SCI group. The TBI+SCI group had longer acute-care LOS. Both groups had similar rehabilitation LOS. Odds of being discharged to nursing homes/long-term care facilities were 1.949 times higher for TBI+SCI individuals. Concomitant TBI did not influence change in ISNCSCI motor subscore from initial admission to final discharge. Odds of individuals with pain was 1.52 times higher for the TBI+SCI group. Occurrence of spasticity was similar between the groups. Conclusion This study highlights discrepancies between the TBI+SCI and SCI-only groups regarding injury epidemiology, survival, discharge disposition, and pain. Both groups experienced similar access to treatment services, motor recovery, and spasticity. Disclosure These data were presented in the 2022 Annual Meeting of the American Neurological Association, which has a different attendance audience.

148th Annual Meeting American Neurological Association.

148th Annual Meeting American Neurological Association.

Developmental milestones as ACNS turns one year old

Developmental milestones as ACNS turns one year old

A Case of Monkeypox-associated Encephalomyelitis—Colorado, July–August, 2022 (P11-10.002)

<h3>Objective:</h3> Monkeypox virus (MPXV) disease was declared a public health emergency by the World Health Organization on July 23, 2022, making it imperative for neurologists to be aware of the potential neurologic implications of this outbreak. To aid in educating neurologists, we present a case of encephalomyelitis in the setting of confirmed MPXV infection. <h3>Background:</h3> MPXV is an orthopox virus in the Poxviridae family, which also includes variola virus (smallpox) and vaccina virus. Prior to May 2022, MPXV was largely confined to Central and Western Africa apart from occasional travel-related cases. However, rapid spread within primarily LGBTQ social networks has created an unexpected pandemic. Occasional reports of encephalitis have been reported in endemic regions with little detail. However, there have been a few reports worldwide of fatal encephalitis in presumed immunocompetent adults in the current pandemic as well as suspected secondary autoimmune encephalomyelitis as reported here. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> A presumed immunocompetent, healthy, gay man in his 30s developed a febrile illness with a diffuse, itchy, vesiculopapular rash followed by progressive left upper and lower extremity weakness/numbness, urinary retention, headache, and intermittent priapism. CSF demonstrated a lymphocytic pleocytosis with elevated protein. Serum HIV antibody and nucleic acid tests were negative. Serum anti-MOG and AQP-4 antibody tests were negative. MRI brain showed multifocal T2/FLAIR subcortical, caudate, thalamic, splenium, and pontine lesions (some of which were partially enhancing). MRI spine showed a longitudinally-extensive, partially enhancing central cord T2 lesion from the cervical cord to conus. MPXV nucleic acid was confirmed from skin lesions but was not present in CSF. His symptoms gradually improved with oral tecovirimat and immunotherapy for suspected para-infectious autoimmune encephalomyelitis. <h3>Conclusions:</h3> MPXV can cause central nervous system disease, whether by direct viral invasion or a para-infectious autoimmune process. With prompt recognition and appropriate treatment, recovery can be achieved. <b>Disclosure:</b> Dr. Money has nothing to disclose. Dr. Hannan has nothing to disclose. Dr. Kleiner has nothing to disclose. Dr. Yuen has nothing to disclose. Mrs. Ferriman has nothing to disclose. Dr. Matthews has nothing to disclose. The institution of Dr. Beckham has received research support from Roche Diagnostics. The institution of Dr. Chauhan has received research support from NIH. The institution of an immediate family member of Dr. Chauhan has received research support from University of Colorado. The institution of Dr. Piquet has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. The institution of Dr. Piquet has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Piquet has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Piquet has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Piquet has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Sands Anderson PC. The institution of Dr. Piquet has received research support from Rocky Mountain MS Center. The institution of Dr. Piquet has received research support from Novartis. The institution of Dr. Piquet has received research support from Abbvie. The institution of Dr. Piquet has received research support from Roche/Genentech. The institution of Dr. Piquet has received research support from NYU. Dr. Piquet has received publishing royalties from a publication relating to health care. Dr. Piquet has received publishing royalties from a publication relating to health care. Dr. Piquet has received personal compensation in the range of $10,000-$49,999 for serving as a Litigative Consultant with US-Dept HHS/DICP. Dr. Tyler has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Protagonist Therapeutics, Newark CA. Dr. Tyler has received personal compensation in the range of $50,000-$99,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Neurological Association/Wiley. Dr. Tyler has received intellectual property interests from a discovery or technology relating to health care. Dr. Tyler has received publishing royalties from a publication relating to health care. Dr. Tyler has a non-compensated relationship as a Director (ex officio) with American Neurological association that is relevant to AAN interests or activities. Dr. Tyler has a non-compensated relationship as a Director with International Society for Neurovirology that is relevant to AAN interests or activities. Dr. Pastula has nothing to disclose.

Impact of Delayed Diagnosis on Zambians Living With Multiple Sclerosis (P4-8.009)

<h3>Objective:</h3> To describe the impact of delayed diagnosis of multiple sclerosis (MS) on Zambians living with MS in Zambia. <h3>Background:</h3> MS is considered rare in African countries such as Zambia leading to significant underdiagnosis in the country. However, recent efforts in the country have shown occurrence among Zambians, with long delays in diagnosis being observed. The impact of this delayed diagnosis on Zambians living with MS remains uninvestigated. <h3>Design/Methods:</h3> One-on-one interviews were conducted with patients that have been diagnosed with MS between 2018 and 2022 by neurologists in Lusaka, Zambia. Prior work showed that these patients had long delays in their MS diagnosis. Interviews were transcribed verbatim and data from the transcripts were categorized by themes of patients’ pre- and post-diagnosis experiences to establish the effects of the delayed diagnosis. <h3>Results:</h3> The delayed diagnosis of MS impacted patients in many ways. These included (1) significant disability at diagnosis; (2) depression and frustration from living with undiagnosed symptoms; (3) loss of employment or income resulting from inability to work due to significant disability; (4) incurring of large costs due to multiple clinical encounters both locally and internationally, often requiring medical tests that were paid for out-of-pocket; (5) loss of confidence in services provided by medical health workers in Zambia, even after MS diagnosis (6) lack of clarity in understanding MS disease severity and the role of neurologists post-diagnosis, often leading to poor compliance to treatment; and (7) significant strain on patients’ families and loved ones. <h3>Conclusions:</h3> Delayed diagnosis of MS negatively impacts the lives of people living with MS in Zambia and leads to low quality of life and significant disability. Efforts to improve early recognition of MS in Zambia are an important element in improving the care of people living with MS in Zambia. <b>Disclosure:</b> Dr. Chomba has nothing to disclose. Dr. Mortel has nothing to disclose. The institution of Dr. Saylor has received research support from National Institutes of Health. The institution of Dr. Saylor has received research support from National Multiple Sclerosis Society. The institution of Dr. Saylor has received research support from American Academy of Neurology. The institution of Dr. Saylor has received research support from United States Department of State. Dr. Saylor has a non-compensated relationship as a Member of multiple committees and task forces focused on improving access to MS medications to people across the world with Multiple Sclerosis International Federation that is relevant to AAN interests or activities. Dr. Saylor has a non-compensated relationship as a Member of the Neurology and COVID19 committee with World Health Organization that is relevant to AAN interests or activities. Dr. Saylor has a non-compensated relationship as a Member of the International Outreach Committee, Junior and Early Career Membership Committee, and Educational Innovation Commitees with American Neurological Association that is relevant to AAN interests or activities.

Correlates of Fluctuations in Moderate-Advanced Dementia with Lewy Bodies (P13-6.007)

<h3>Objective:</h3> To assess correlates of fluctuations in moderate-advanced dementia with Lewy bodies [DLB]. <h3>Background:</h3> Cognitive fluctuations (spontaneous episodic deficits in attention, arousal, cognition, and behavior) are a core DLB feature, but remain poorly understood. <h3>Design/Methods:</h3> The PACE-DLB study collected measures of Lewy body disease, demographics, and patient and caregiver experiences from moderate-advanced DLB individual-caregiver dyads. Fluctuations were assessed via the Mayo Fluctuations Scale (MFS, range 0–4) and Clinician Assessment of Fluctuation (CAF, range 0–16). Concordance was assessed using Spearman correlation for raw scores and Cohen’s Kappa for assessing scores above/below the cut-off. Nonparametric methods including Spearman correlation, two-sample Wilcoxon test, and odds ratios assessed factors associated with fluctuations. The FDR method corrected raw scores for multiple testing. <h3>Results:</h3> Patients (n=137) identified as white non-Hispanic (94.9%) and male (79.6%); mean age 75.0 (SD 8.0), disease duration 3.0 years (SD 2.4). Caregivers were typically wives (72.3%) and daughters (13.1%). On the MFS, 116 participants (84.7%) had fluctuations (score ≥3) (mean 3.3, SD 0.8) versus 116 (84.7%) on the CAF (score &gt;0) (correlation: 0.2, p&lt;0.001; fluctuations absent/present: 0.3, p=0.002). The mean CAF score was 8.8 (SD 6.6). Variables associated with a positive MFS included higher sleepiness scores (p=0.02), lower QoL-AD scores (p=0.02), and parkinsonism (p=0.02). No variables associated with a positive CAF. Higher MFS scores associated with higher sleepiness scores (p&lt;0.001), lower QoL-AD, and more autonomic symptoms (p=0.03). Higher CAF scores associated with higher Neuropsychiatric Inventory severity scores (p&lt;0.0001), hallucinations (p=0.045), orthostatic hypotension (p=0.02), more comorbidities (p=0.04), and higher sleepiness scores (p=0.045). Fluctuations associated with worse patient and caregiver quality of life and higher caregiver burden and depression. <h3>Conclusions:</h3> The MFS and CAF correlated weakly. Fluctuations associated with sleepiness, autonomic symptoms, parkinsonism, and neuropsychiatric symptoms. Given the impact of fluctuations on quality of life and caregiver burden and depression, fluctuations are an important target for future pharmacologic therapies. <b>Disclosure:</b> Dr. Tholanikunnel has nothing to disclose. Mr. LaBarre has nothing to disclose. Ms. Sovich has nothing to disclose. Li Zhigang has nothing to disclose. James Galvin has nothing to disclose. Dr. Paulson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Exicure. The institution of Dr. Paulson has received research support from National Institutes of Health. Dr. Paulson has a non-compensated relationship as a Member, Nominating committee with American Neurological Association that is relevant to AAN interests or activities. An immediate family member of Dr. Maixner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Law office . The institution of Dr. Manning has received research support from Department of Defense. The institution of Dr. Fields has received research support from National Institutes of Health. The institution of Dr. Fields has received research support from Patient-Centered Outcomes Research Institute. Ms. Lunde has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Mayo Clinic . Dr. Boeve has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Rainwater Charitable Foundation. The institution of Dr. Boeve has received research support from Alector. The institution of Dr. Boeve has received research support from GE Healthcare. The institution of Dr. Boeve has received research support from Transposon. The institution of Dr. Boeve has received research support from Cognition Therapeutics. Dr. Boeve has received publishing royalties from a publication relating to health care. Ms. Forsberg has nothing to disclose. Angela Taylor has received personal compensation for serving as an employee of Lewy Body Dementia Association . The institution of Dr. Armstrong has received research support from National Institute of Aging. The institution of Dr. Armstrong has received research support from Florida Department of Health. The institution of Dr. Armstrong has received research support from Lewy Body Dementia Association. Dr. Armstrong has received research support from Parkinson Foundation. Dr. Armstrong has received personal compensation in the range of $5,000-$9,999 for serving as a DSMB member with Alzheimer’s Clinical Trials Consortium. Dr. Armstrong has received personal compensation in the range of $5,000-$9,999 for serving as a DSMB member with Alzheimer’s Disease Cooperative Study. Dr. Armstrong has a non-compensated relationship as a Member, Scientific Advisory Council with Lewy Body Dementia Association that is relevant to AAN interests or activities.

More Than Meets the Eye: A Closer Look At Demyelinating Diseases In Zambia (P4-8.015)

<h3>Objective:</h3> Describe demographic and clinical characteristics of Zambian adults with MS and neuromyelitis optica (NMO). <h3>Background:</h3> MS and other demyelinating diseases are reportedly rare in sub-Saharan Africa and remain understudied. <h3>Design/Methods:</h3> Adults diagnosed with either MS, NMO, NMO spectrum disorder (NMOSD), or clinically isolated syndrome (CIS) at the only neurology outpatient clinic in Zambia were eligible to participate from October 2019 to February 2022. An MS-trained nurse administered structured questionnaires regarding sociodemographic characteristics, and each participant also underwent a comprehensive neurological history and examination by a neurologist. Finally, plasma 25-hydroxyvitamin D levels were obtained. For analysis, the cohort was dichotimized into a MS/CIS disease group and NMO/NMOSD disease group. Descriptive statistics of the cohort are presented and compared between both groups. <h3>Results:</h3> Amongst the 34 participants, mean age was 36 + 9 years, 65% (n=22) were female, 90% were Black-African, 10% were of Southeast Asian decent, 50% had MS/CIS, and 50% had NMO/NMOSD. The average age was 34 + 11 years in the MS/CIS group and 37 + 7 years in the NMO/NMOSD group (p=0.28). Females constituted 65% (n=11) of both disease groups. Median time to diagnosis was 242 days (interquartile range IQR: 91–974) and did not differ significantly between the groups. The majority (82%) of the NMO/NMOSD group presented with bilateral optic neuritis. Among the MS/CIS group, median EDSS was 4 (IQR: 2.25–4.25), median Disease Steps were 2 (IQR: 1–2), and 59% (n=10) had an abnormal gait at enrollment. Median 25-hydroxyvitamin D level was 29 (IQR: 24–46) ng/mL in the overall cohort but did not differ by disease group or supplementation status. <h3>Conclusions:</h3> In this sub-Saharan African cohort of adults with demyelinating diseases, MS and NMO were equally prevalent. Delays in diagnosis resulted in high levels of disability in both groups. <b>Disclosure:</b> Dr. Mortel has nothing to disclose. Dr. Braun has received research support from Zambart. Dr. Chishimba has nothing to disclose. Dr. Chomba has nothing to disclose. Dr. Mutete has nothing to disclose. NALUCA MWENDAWELI has nothing to disclose. Dr. Namangala has nothing to disclose. Dr. Zimba has nothing to disclose. The institution of Dr. Saylor has received research support from National Institutes of Health. The institution of Dr. Saylor has received research support from National Multiple Sclerosis Society. The institution of Dr. Saylor has received research support from American Academy of Neurology. The institution of Dr. Saylor has received research support from United States Department of State. Dr. Saylor has a non-compensated relationship as a Member of multiple committees and task forces focused on improving access to MS medications to people across the world with Multiple Sclerosis International Federation that is relevant to AAN interests or activities. Dr. Saylor has a non-compensated relationship as a Member of the Neurology and COVID19 committee with World Health Organization that is relevant to AAN interests or activities. Dr. Saylor has a non-compensated relationship as a Member of the International Outreach Committee, Junior and Early Career Membership Committee, and Educational Innovation Commitees with American Neurological Association that is relevant to AAN interests or activities.

MOG Antibody-Associated Bilateral Optic Neuritis Associated with Johnson and Johnson COVID-19 Vaccination (P12-3.009)

<h3>Objective:</h3> To describe a case of bilateral optic neuritis associated with MOG Antibodies following vaccination with Johnson and Johnson (J&amp;J) COVID-19 vaccine. <h3>Background:</h3> Cases of MOG Antibody Disease (MOGAD) following infection or vaccination have been reported, including in association with both COVID-19 infection and vaccination. However, no cases have been reported in Africa, associated with the J&amp;J vaccine or presenting with bilateral optic neuritis. <h3>Design/Methods:</h3> NA <h3>Results:</h3> A 37-year-old Zambian woman presented two weeks after vaccination with the J &amp; J COVID-19 vaccine with progressive vision loss and headache associated with eye movement. Loss of color vision developed a week later and progressed over four days to complete blindness. On examination, she had no light perception in both eyes, dilated pupils with sluggish light reflex, and bilateral papilledema. The remainder of her examination was normal. Baseline investigations were unremarkable, and MRI and MRV of the brain were normal. Orbital MRI was not available in our setting. OCT showed bilateral thickening of the retinal nerve fiber layer with nasal depression of the macular ganglion cell inner plexiform layer. Serum aquaporin-4 antibodies were negative, and serum MOG antibodies were positive. The patient received a 5-day course of pulse-dose steroids followed by 1mg/kg oral prednisolone tapered over 8 weeks. She experienced full recovery of her visual acuity within 10 days of pulse-dose steroids and remained relapse free for six months. <h3>Conclusions:</h3> This case of MOG-antibody associated bilateral optic neuritis triggered by J&amp;J COVID-19 vaccine in a Zambian woman is unique in that the diagnosis was made in a resource limited setting, necessitating a high index of suspicion, reliance on clinical skills and highly targeted testing. This case further highlights the need for surveillance for similar cases and it adds literature of cases of MOGAD associated with various COVID-19 vaccines. <b>Disclosure:</b> Dr. Mutete has nothing to disclose. NALUCA MWENDAWELI has nothing to disclose. Dr. Asukile has nothing to disclose. Dr. Serenje has received research support from Orbis International. Willard Mumbi has nothing to disclose. The institution of Dr. Saylor has received research support from National Institutes of Health. The institution of Dr. Saylor has received research support from National Multiple Sclerosis Society. The institution of Dr. Saylor has received research support from American Academy of Neurology. The institution of Dr. Saylor has received research support from United States Department of State. Dr. Saylor has a non-compensated relationship as a Member of multiple committees and task forces focused on improving access to MS medications to people across the world with Multiple Sclerosis International Federation that is relevant to AAN interests or activities. Dr. Saylor has a non-compensated relationship as a Member of the Neurology and COVID19 committee with World Health Organization that is relevant to AAN interests or activities. Dr. Saylor has a non-compensated relationship as a Member of the International Outreach Committee, Junior and Early Career Membership Committee, and Educational Innovation Commitees with American Neurological Association that is relevant to AAN interests or activities.

Prevalence of Peripheral Nervous System Involvement in Adult Leukodystrophies (P2-5.031)

<h3>Objective:</h3> na <h3>Background:</h3> Leukodystrophies are genetic, neurodegenerative white matter diseases of the central nervous system (CNS) caused by mutations in various genes, presenting with heterogeneous clinical features and age of onset. It is well established that some leukodystrophies have peripheral nervous system (PNS) involvement, whether demyelinating, axonal or mixed in pathology. However, the prevalence of peripheral neuropathy in adult leukodystrophies is unknown. Early recognition of PNS involvement in these disorders is imperative to enable appropriate management and care of the symptoms. <h3>Design/Methods:</h3> We performed a retrospective review of all adult subjects followed at our two institutions for white matter disease of genetic origin to select patients with evidence of PNS involvement as documented by nerve conduction studies (NCS) and/or electromyography (EMG)For these subjects we collected and analyzed data on sociodemographic status, family history, clinical characteristics, and disease course, nerve conduction studies (NCS), electromyography (EMG), MRI features and genetic testing results. <h3>Results:</h3> From our combined cohorts of 161 adult subjects followed for genetic white matter diseases, we identified 14 patients (8.7%) with documented PNS involvement. A definite genetic diagnosis was established in 5 subjects (3 with adult polyglucosan body disease, 1 with metachromatic leukodystrophy, 1 with POLR3-related disorder) while 9 subjects remained undiagnosed despite extensive genetic investigations. The demographic, clinical, radiological, and electrophysiological data will be presented. <h3>Conclusions:</h3> This is the first study conducted to assess the prevalence of peripheral neuropathy in adult patients with leukodystrophy. In our two independent cohorts, PNS involvement is rare, however, early recognition of the concurrence of CNS and PNS involvement is essential to plan appropriate management of the patients’ symptomatic care and is key as more treatment options are becoming available. <b>Disclosure:</b> Dr. Alsabah has nothing to disclose. Dr. Hasiloglu has nothing to disclose. Dr. Massie has received personal compensation in the range of $500-$4,999 for serving as a Expert consultant with INESS (Quebec Public Health agency). Dr. Massie has received personal compensation in the range of $500-$4,999 for serving as a Lecturer with Amylyx Pharmaceuticals. Dr. Brais has nothing to disclose. Dr. Orthmann Murphy has received research support from Conrad N. Hilton Foundation. Dr. Orthmann Murphy has received research support from Institute for Translational Medicine and Therapeutics’ (ITMAT) Transdisciplinary Program in Translational Medicine and Therapeutics, University of Pennsylvania. The institution of Dr. Orthmann Murphy has received research support from Vigil Neurosciences. The institution of Dr. Orthmann Murphy has received research support from National MS Society. Dr. Orthmann Murphy has received personal compensation in the range of $500-$4,999 for serving as a Invited Speaker with Temple University . Dr. Orthmann Murphy has received personal compensation in the range of $0-$499 for serving as a Consultant with American Neurological Association. Roberta La Piana has nothing to disclose.

Multiple Sclerosis Research Across the African Continent: A Systematic Review (P5-3.002)

<h3>Objective:</h3> To summarize the contemporary state of MS research across the African continent and to identify knowledge gaps from the current research landscape. <h3>Background:</h3> MS remains considered a rare neurological disorder among African populations, despite the fact that original MS research based in African countries is extremely limited or non-existent. <h3>Design/Methods:</h3> Boolean searches on the PubMed, SCOPUS and Embase databases were conducted for articles published from 1990 to February 2022. Two reviewers evaluated the title and abstract of each identified record for inclusion based on pre-defined eligibility criteria. Discrepancies between reviewers were resolved by discussion until consensus was reached. Full-text review and data extraction were conducted by a single reviewer for all articles which passed the initial title and abstract screening process. <h3>Results:</h3> After removal of duplicates, 2491 records were initially identified and underwent screening. 332 records were then selected for full-text review and 251 were deemed eligible for inclusion. The majority of included studies were from the Northern African region (<i>n</i>=204; 81%), particularly from Egypt (<i>n</i>=166; 66%), and had a case-control study design (<i>n</i>=145; 58%). Studies based in Egypt, Tunisia and South Africa accounted for ≥90% of included studies. Over 50% (<i>n</i>=150) of selected studies were published from 2016–2022, highlighting the substantial increase in research output in recent years. Studies investigating the utility of diagnostic tools (i.e. blood/serum biomarkers and neuroimaging technology) were most common (<i>n</i>=105; 42%), followed by studies investigating MS risk factors (<i>n</i>=41; 16%). <h3>Conclusions:</h3> The majority of MS research from the African continent comes from only a few countries with virtually no data from the majority of African countries. Notable gaps and barriers in our knowledge of the burden of MS in Africa remain, and further efforts to promote clinical and epidemiological MS research in sub-Saharan Africa are needed to improve our understanding of the burden of MS amongst African patients. <b>Disclosure:</b> Mr. Hwang has nothing to disclose. The institution of Dr. George has received research support from Biogen. Dr. Garcia-Dominguez has nothing to disclose. Dr. Salasky has nothing to disclose. The institution of Dr. Vishnevetsky has received research support from National MS Society. The institution of Dr. Vishnevetsky has received research support from NIH (NeuroNext). Dr. Miskin has nothing to disclose. Andy Tran has nothing to disclose. Dr. Chiluba has nothing to disclose. The institution of Dr. Saylor has received research support from National Institutes of Health. The institution of Dr. Saylor has received research support from National Multiple Sclerosis Society. The institution of Dr. Saylor has received research support from American Academy of Neurology. The institution of Dr. Saylor has received research support from United States Department of State. Dr. Saylor has a non-compensated relationship as a Member of multiple committees and task forces focused on improving access to MS medications to people across the world with Multiple Sclerosis International Federation that is relevant to AAN interests or activities. Dr. Saylor has a non-compensated relationship as a Member of the Neurology and COVID19 committee with World Health Organization that is relevant to AAN interests or activities. Dr. Saylor has a non-compensated relationship as a Member of the International Outreach Committee, Junior and Early Career Membership Committee, and Educational Innovation Commitees with American Neurological Association that is relevant to AAN interests or activities.

Radiological features of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and its longitudinal progression (P8-4.003)

Radiological features of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and its longitudinal progression (P8-4.003)

Parkinsonism in a Zambian Man with an unusual occupational exposure (P3-4.002)

<h3>Objective:</h3> Describe a case of Manganism encountered in Zambia. <h3>Background:</h3> Manganism is a neurodegenerative syndrome due to manganese toxicity and its excessive accumulation in the brain. <h3>Design/Methods:</h3> Case presentation <h3>Results:</h3> A 37-year-old man presented with a four-month history of mild, intermittent headache and three-month history of chest pain, dry cough and symmetrical distal-predominant paresthesias. He developed progressive cognitive decline associated with slowness in talking, low volume speech and difficulty completing activities of daily living two months prior to presentation. He reported fever and night sweats. Past medical history was unremarkable. Social history only notable for working as a manganese smelter for the past eight years. Neurological exam revealed memory and language deficits with psychomotor slowing, subtle left upper motor neuron facial weakness, hypomimia, bradykinesia and had a hyperkinetic tongue and upper limb tremor with normal tone and power in all limbs. Deep tendon reflexes were normal, but frontal release signs and an applause sign were present. Small and large fiber length-dependent sensory loss was noted with a cock-walk gait. MRI brain with gadolinium showed non-enhancing symmetric T1 hyperintensities in the globus pallidum and midbrain with corresponding T2 hypointensities in the same areas. <h3>Conclusions:</h3> A diagnosis of Manganism was made based on clinical history, strong occupational exposures, and neurological examination and imaging findings. Blood manganese levels and other heavy metals could not be obtained due to unavailability of tests in our setting, although blood manganese levels are often normal when obtained in cases of Manganism. The cough, headache, chest pain and fever were ascribed to metal fume fever and improved after a three-month withdrawal of manganese exposure, though neurologic symptoms did not improve during this period. This case demonstrates the importance of thorough history (including social history), examination, and correlation with limited investigations in diagnosing even rare diseases in resource-limited settings. <b>Disclosure:</b> Dr. Munkombwe has nothing to disclose. Dr. Asukile has nothing to disclose. Dr. Schwab has nothing to disclose. The institution of Dr. Saylor has received research support from National Institutes of Health. The institution of Dr. Saylor has received research support from National Multiple Sclerosis Society. The institution of Dr. Saylor has received research support from American Academy of Neurology. The institution of Dr. Saylor has received research support from United States Department of State. Dr. Saylor has a non-compensated relationship as a Member of multiple committees and task forces focused on improving access to MS medications to people across the world with Multiple Sclerosis International Federation that is relevant to AAN interests or activities. Dr. Saylor has a non-compensated relationship as a Member of the Neurology and COVID19 committee with World Health Organization that is relevant to AAN interests or activities. Dr. Saylor has a non-compensated relationship as a Member of the International Outreach Committee, Junior and Early Career Membership Committee, and Educational Innovation Commitees with American Neurological Association that is relevant to AAN interests or activities.

Evaluation of Three Cohorts of the First Neurology Postgraduate Training Program in Zambia (P4-8.001)

<h3>Objective:</h3> Identify strengths, areas for improvement and perceptions of a new neurology training program in Zambia. <h3>Background:</h3> The first Zambian neurology training program commenced in 2018. We report its first programmatic evaluation. <h3>Design/Methods:</h3> All current and former neurology trainees, internal medicine (IM) trainees who rotated with neurology in the past year, all IM faculty, and all international visiting providers from the past four years were sent electronic surveys. Neurology trainees and graduates, IM rotators, international faculty who had visited for at least three months, and one hospital administrator were invited to focus groups or semi-structured interviews. Participants were asked what they perceived as the “most significant change” at the hospital since program implementation. <h3>Results:</h3> 62/78 (80%) completed surveys, 17 contributed to focus groups and interviews. Neurology trainees noted protected didactic time, emphasis on bedside teaching, and one-on-one attending exposure were program strengths and requested more exposure to outpatient subspecialties and electrophysiology training. When asked about the “most significant change”, participants noted providers in other specialties across the hospital also seemed to be learning neurologic examination and diagnostic skills, leading to widely improved neurologic care. Additionally, they noted a stronger research emphasis among trainees, even those outside neurology. <h3>Conclusions:</h3> The Zambian neurology training program has created positive department-wide changes in teaching and research. Other training programs in resource-limited settings may benefit from prioritizing one-on-one bedside teaching and protected didactics. Similarly, trainees in resource-limited settings may benefit from the development of regional collaborations to provide better exposure to subspecialty clinical experiences and mentors that may be limited at single institutions. Our study employed a comprehensive, mixed-methods approach to program evaluation in this resource-limited setting that identified strengths and actionable solutions to areas for improvement. This program evaluation method could provide valuable insights in other training settings, regardless of available resources. <b>Disclosure:</b> Dr. DiBiase has nothing to disclose. Edford Sinkala has nothing to disclose. Dr. Jonathan has nothing to disclose. The institution of Sean Tackett has received research support from NIH. The institution of Dr. Saylor has received research support from National Institutes of Health. The institution of Dr. Saylor has received research support from National Multiple Sclerosis Society. The institution of Dr. Saylor has received research support from American Academy of Neurology. The institution of Dr. Saylor has received research support from United States Department of State. Dr. Saylor has a non-compensated relationship as a Member of multiple committees and task forces focused on improving access to MS medications to people across the world with Multiple Sclerosis International Federation that is relevant to AAN interests or activities. Dr. Saylor has a non-compensated relationship as a Member of the Neurology and COVID19 committee with World Health Organization that is relevant to AAN interests or activities. Dr. Saylor has a non-compensated relationship as a Member of the International Outreach Committee, Junior and Early Career Membership Committee, and Educational Innovation Commitees with American Neurological Association that is relevant to AAN interests or activities.

Evaluating the Experience of Visiting International Providers on Local Neurology Trainees in a Resource-Limited Setting (P4-8.007)

<h3>Objective:</h3> Assess the impact of visiting international neurology attendings and trainees on local neurology trainees in Zambia. <h3>Background:</h3> Interest in global neurology is increasing among U.S. neurology residents. Global health electives improve clinical skills, commitment to underserved populations, and cost-effective decision-making practices among neurology trainees from high-income settings. However, existing literature focuses primarily on the experiences of Canadian and U.S. trainees, with formal research on the perspective of local neurology trainees lacking. <h3>Design/Methods:</h3> The Zambian neurology training program, which graduated its first class in 2018, frequently hosts visiting neurology attendings and residents from high-income settings. Current trainees and graduates of the program completed surveys and participated in focus groups to assess their experiences with visitors and the impact on their training. <h3>Results:</h3> 100% of current trainees (n=5) and program graduates (n=4) participated. All participants rated the experience of working with international visitors positively (56% rated 5/5 (most positive), 44% rated 4/5). Specific positive aspects included exposure to different teaching styles and clinical approaches, awareness of neurologic practice in different parts of the world, expertise in subspecialties less available locally, and expanded academic networking opportunities. Local trainees appreciated the clinical contribution to busy inpatient and outpatient services, the ability to compare themselves to an “international standard”, and the cultural exchange with visitors. Challenges of working with visitors included occasional discrepancies in expectations, prolonged patient encounters due to language barriers, incomplete understanding by visitors of cultural differences and resource limitations, and physical workspace constraints. <h3>Conclusions:</h3> Local trainees in Zambia reported an overall positive experience with visiting providers from high-income countries. Our results provide support for expanding global health electives and faculty opportunities in Zambia and, potentially, similar settings. Orientation sessions for visiting clinicians to review cultural differences, resource limitations, and training expectations may improve the experience for visitors and hosts alike. <b>Disclosure:</b> Dr. Salasky has nothing to disclose. Dr. DiBiase has nothing to disclose. The institution of Dr. Saylor has received research support from National Institutes of Health. The institution of Dr. Saylor has received research support from National Multiple Sclerosis Society. The institution of Dr. Saylor has received research support from American Academy of Neurology. The institution of Dr. Saylor has received research support from United States Department of State. Dr. Saylor has a non-compensated relationship as a Member of multiple committees and task forces focused on improving access to MS medications to people across the world with Multiple Sclerosis International Federation that is relevant to AAN interests or activities. Dr. Saylor has a non-compensated relationship as a Member of the Neurology and COVID19 committee with World Health Organization that is relevant to AAN interests or activities. Dr. Saylor has a non-compensated relationship as a Member of the International Outreach Committee, Junior and Early Career Membership Committee, and Educational Innovation Commitees with American Neurological Association that is relevant to AAN interests or activities.

Patient Feedback for a Neurology Specialty Clinic with a “Provider Continuity” Model in Lusaka, Zambia (P4-8.012)

<h3>Objective:</h3> Assess patient satisfaction with the only neurology clinic in Zambia. <h3>Background:</h3> Zambia’s only outpatient neurology clinic operates two mornings weekly with approximately 50 patients seen each day on a first come-first served basis. In 2018, neurology residents were incorporated as providers within the clinic. Formal feedback has not been previously solicited from patients. <h3>Design/Methods:</h3> We distributed surveys in English, Nyanja and Bemba to patients in the neurology clinic over four weeks. No identifying information was collected, and participant responses were entered into a Qualtrics database. <h3>Results:</h3> 191 patients participated. Since attending the clinic, 46% reported understanding of their diagnoses improved, 20% reported medication modifications, 18% motor improvement or re-gained ambulation, and 14% better seizure control. The majority were at least “somewhat satisfied” with competence (89%) and communication skills (86%) of clinic doctors, time spent with the physician (90%), and with their follow-up plan (82%). When asked to compare the neurology clinic to other clinics they attended, patients reported superior diagnostics and treatment options, better physician bedside manner, and more time spent with patients. Half of participants were at least “somewhat unsatisfied” with wait times to be seen after arriving at the clinic. Still, most (56%) preferred to see the same neurologist each visit, while 17% preferred to see the first available provider and the rest were undecided/ambivalent. <h3>Conclusions:</h3> The Zambian neurology clinic provides diagnostic clarity for patients and better satisfaction with treatment plans and patient/doctor relationships than other clinics. Despite prolonged wait times, most patients preferred provider continuity over expedited care. Thus, hospitals in resource-limited settings should consider introducing specialist public sector clinics whenever possible and replacing “first available provider” models with “provider continuity” models to improve clinical care and patient satisfaction. Providing formal appointment times in lieu of a first come-first served appointment model may also improve patient satisfaction. <b>Disclosure:</b> Dr. DiBiase has nothing to disclose. The institution of Dr. Chiwaya has received research support from National Institute of Health . Mr. Giauque has nothing to disclose. The institution of Dr. Saylor has received research support from National Institutes of Health. The institution of Dr. Saylor has received research support from National Multiple Sclerosis Society. The institution of Dr. Saylor has received research support from American Academy of Neurology. The institution of Dr. Saylor has received research support from United States Department of State. Dr. Saylor has a non-compensated relationship as a Member of multiple committees and task forces focused on improving access to MS medications to people across the world with Multiple Sclerosis International Federation that is relevant to AAN interests or activities. Dr. Saylor has a non-compensated relationship as a Member of the Neurology and COVID19 committee with World Health Organization that is relevant to AAN interests or activities. Dr. Saylor has a non-compensated relationship as a Member of the International Outreach Committee, Junior and Early Career Membership Committee, and Educational Innovation Commitees with American Neurological Association that is relevant to AAN interests or activities.

A Prospective Natural History Study of Patients with Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia (ALSP) (S49.008)

A Prospective Natural History Study of Patients with Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia (ALSP) (S49.008)

Editorial introductions.

Current Opinion in Neurology was launched in 1988. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of neurology is divided into 14 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS Lawrence J. HirschLawrence J. HirschLawrence J. Hirsch, MD is Professor of Neurology, Chief of the Division of Epilepsy and EEG, and Co-Director of the Comprehensive Epilepsy Center, all at Yale University, USA. He has held leadership positions in the American Clinical Neurophysiology Society (ACNS), American Epilepsy Society, American Academy of Neurology, and the Epilepsy Foundation, and is lead author of the 2012 and 2021 ACNS guidelines on critical care EEG terminology. He is founder and former chair of the Critical Care EEG Monitoring Research Consortium, which now includes more than 50 centers, and co-chair of the medical advisory board of the NORSE Institute. He has been an active researcher throughout his career, having published more than 200 peer-reviewed manuscripts and more than 100 reviews, editorials or book chapters on topics including status epilepticus, all aspects of EEG including intracranial recordings and brain monitoring in the critically ill, brain stimulation, epilepsy surgery, seizure clusters, rescue medications, sudden death in epilepsy (SUDEP), and anti-seizure medication use. He has won multiple teaching awards and is co-author of the first-ever atlas on EEG in critical care, now in its 2nd edition. He continues to see patients in the inpatient and outpatient setting, direct fellowship programs, teach, mentor, and manage a large epilepsy division at a level IV Comprehensive Epilepsy Center. Michael F. WatersMichael F. WatersMichael F. Waters, MD, PhD, is a neurologist, director of both the Neurovascular Division and the Petznick Stroke Center, and a professor in the Department of Neurology at Barrow Neurological Institute, USA. He is board certified in neurology by the American Board of Psychiatry and Neurology with subspecialty board certification in vascular neurology. Dr Waters’ expertise is stroke and neurovascular disease, including signs, symptoms, diagnostics, and treatments. He is a fellow of both the American Academy of Neurology and American Heart Association and a member of the American Neurological Association, American Society of Human Genetics, and the Society of Vascular and Interventional Neurology. Dr Waters received his Masters in genetics from Penn State University in State College, Pennsylvania, USA, and his doctorate in biochemistry and molecular biology from The University of Florida College of Medicine in Gainesville, USA, where he also completed his MD. He completed his residency training at the University of California – Los Angeles Department of Neurology and completed his fellowship in clinical and molecular neurogenetics at Cedars Sinai Medical Center in Los Angeles, USA. Dr Waters’ research studies include genetic mechanisms of stroke, neuroprotection in stroke, stroke treatment, multiple clinical trials investigating stroke treatments, and neurogenetic mechanisms of neuroplasticity.