Interstitial amyloidosis in sporadic inclusion body myositis.

INTRODUCTION/AIMS: Intracellular congophilic inclusions within muscle fibers, although nonspecific, are one of the pathological hallmarks of sporadic inclusion body myositis (sIBM). Extracellular amyloid deposits in muscle, on the other hand, are the canonical findings of amyloid myopathies, which occur with or without systemic amyloidosis. METHODS: We reviewed the muscle biopsy database (1998-2020) to identify sIBM patients with extracellular amyloid deposits. Clinical and laboratory data were reviewed. RESULTS: We identified five sIBM patients (three clinicopathologically defined and two clinically defined) with extracellular amyloid deposits in muscle. Mean age at diagnosis was 74.8 y (range, 68-84 y). All patients had a typical sIBM pattern of weakness without associated sensory or autonomic symptoms. None had electrophysiological evidence of peripheral neuropathy. Only one patient had a monoclonal gammopathy (immunoglobulin M-lambda, IgM-λ) with normal bone marrow biopsy. This patient with monoclonal gammopathy and three other patients underwent abdominal fat pad aspirate and were negative for amyloid. Cardiac evaluation was unrevealing in the four patients tested. Three patients without monoclonal gammopathy had normal transthyretin gene sequencing and inconclusive mass spectrometry-based analysis. The patient with monoclonal gammopathy died of pneumosepsis 5 y after diagnosis and autopsy revealed multi-organ transthyretin amyloidosis. DISCUSSION: Detection of extracellular amyloid deposition in muscle should trigger an aggressive search for systemic amyloidosis independently from other associated myopathological abnormalities. Amyloid subtyping is crucial for early therapy and mortality prevention. An isolated monoclonal gammopathy should not halt a search for non-hematological causes of systemic amyloidosis.

Assessment in Neurologic Education.

Neurology trainee assessment is a required component of the education feedback loop, allowing programs and trainees to measure their progress toward established educational goals. In the era of competency-based medical education, assessment systems should be designed to inform decisions about each trainee's acquisition of the many competencies required for independent clinical neurology practice. In addition to the need to inform trainees and programs regarding trainee performance, assessment systems must be equipped to satisfy requirements established by accrediting bodies. Educational goals should be thoughtfully established prior to assessment system design to ensure that assessment priorities align with the overall goal of equipping graduates to deliver high-quality neurologic care. This article provides an overview of modern principles of medical education as they can be applied to neurologic education, complemented by practical recommendations for neurologic educators to develop or improve assessment systems within their own training programs.

The value transformation of health care: Impact on neuromuscular and electrodiagnostic medicine.

Beginning in 2017, most physicians who participate in Medicare are subject to the Medicare Access and CHIP Reauthorization Act (MACRA), the milestone legislation that signals the US health care system's transition from volume-based to value-based care. Here we review emerging trends in development of value-based healthcare systems in the US. MACRA and the resulting Quality Payment Program create 2 participation pathways, the Merit-based Incentive Payment System (MIPS) and the Advanced Alternative Payment Model (AAPM) pathway. Although there are several program incentives for AAPM participation, to date there have been few AAPM options for specialists. MIPS and its widening bonus and penalty window will likely be the primary participation pathway in the early years of the program. Value-based payment has the potential to reshape health care delivery in the United States, with implications for neuromuscular and electrodiagnostic (EDX) specialists. Meaningful quality measures are required for neuromuscular and EDX specialists. Muscle Nerve 56: 679-683, 2017.

Clinical spectrum of valosin containing protein (VCP)-opathy.

INTRODUCTION: Valosin containing protein (VCP) mutations cause a rare disorder characterized by hereditary inclusion body myopathy, Paget disease of bone (PDB), and frontotemporal dementia (FTD) with variable penetrance. VCP mutations have also been linked to amyotrophic lateral sclerosis and Charcot-Marie-Tooth disease type 2. METHODS: Review of clinical, serological, electrophysiological, and myopathological findings of 6 VCP-opathy patients from 4 unrelated families. RESULTS: Patients manifested muscle weakness between ages 40 and 53 years and developed predominant asymmetric limb girdle weakness. One patient had distal weakness at onset and co-existing peripheral neuropathy. Another patient had PDB, 1 had mild cognitive deficits, and 1 had FTD. All patients had myopathic and neurogenic electromyographic findings with predominant neurogenic changes in 2. Rimmed vacuoles were infrequent, while neurogenic changes were prominent in muscle biopsies. CONCLUSIONS: VCP-opathy is a multifaceted disorder in which myopathy and peripheral neuropathy can coexist. The electrophysiological and pathological neurogenic changes raise the possibility of coexisting motor neuron involvement. Muscle Nerve, 2015 Muscle Nerve 54: 94-99, 2016 Muscle Nerve 54: 94-99, 2016.

Clinical, electrophysiologic, and imaging features of zoster-associated limb paresis.

INTRODUCTION: Paresis is a long-recognized complication of herpes zoster, but there has been comparatively little study of zoster-associated limb paresis (ZALP). METHODS: In this study we reviewed 49 Mayo Clinic patients with ZALP. RESULTS: The mean age of onset was 71 years, 67% were men, and the lower limb was affected in 55%. The mean weakness score was 2.0 (0 = normal strength, 4 = plegia). Most patients developed postherpetic neuralgia (PHN, 92% at 1 month and 65% at 3 months), and the average minimum duration of weakness was 193 days. ZALP was caused by radiculopathy (37%), plexopathy (41%), mononeuropathy (14%), and radiculoplexus neuropathy (8%). MRI demonstrated nerve enlargement, T2 signal prolongation, or enhancement in a majority (64%) of affected plexi and peripheral nerves. CONCLUSIONS: ZALP is associated with considerable weakness. It typically lasts at least several months, localizes to plexus or peripheral nerve in 63%, and is associated with high rates of PHN.

Cramp-fasciculation syndrome in patients with and without neural autoantibodies.

INTRODUCTION: We investigated the clinical, electrophysiological and neural autoantibody characteristics in cramp-fasciculation syndrome (CFS) patients. METHODS: We reviewed Mayo Clinic records from 2000 to 2011 to identify clinically defined CFS patients who underwent neural autoantibody testing. Stored sera of patients who tested positive for antibodies to voltage-gated potassium channel complex (VGKC complex) were analyzed further for leucine-rich glioma-inactivated 1 (LGI1) or contactin-associated protein-2 immunoglobulin G (CASPR2-IgG) antibodies. RESULTS: Thirty-seven patients were identified. Twelve were seropositive for neural autoantibodies. Clinical manifestations were similar in seropositive and seronegative patients, although central and autonomic neuronal hyperexcitability symptoms were more common in seropositive cases. No patients had a malignancy. Repetitive tibial nerve stimulation at 10 Hz revealed longer afterdischarges in seropositive patients. Two of 7 patients with VGKC-complex autoimmunity demonstrated LGI1 or CASPR2-IgG antibodies. Only 2 of 12 seropositive patients required immunotherapy. CONCLUSIONS: VGKC-complex autoimmunity occurs in a minority of CFS patients. Antibody positivity was associated with extramuscular manifestations, typically without malignancy. Target antigens within the VGKC complex remain unknown in most patients.

Implications of Large Language Models for Quality and Efficiency of Neurologic Care: Emerging Issues in Neurology.

Large language models (LLMs) are advanced artificial intelligence (AI) systems that excel in recognizing and generating human-like language, possibly serving as valuable tools for neurology-related information tasks. Although LLMs have shown remarkable potential in various areas, their performance in the dynamic environment of daily clinical practice remains uncertain. This article outlines multiple limitations and challenges of using LLMs in clinical settings that need to be addressed, including limited clinical reasoning, variable reliability and accuracy, reproducibility bias, self-serving bias, sponsorship bias, and potential for exacerbating health care disparities. These challenges are further compounded by practical business considerations and infrastructure requirements, including associated costs. To overcome these hurdles and harness the potential of LLMs effectively, this article includes considerations for health care organizations, researchers, and neurologists contemplating the use of LLMs in clinical practice. It is essential for health care organizations to cultivate a culture that welcomes AI solutions and aligns them seamlessly with health care operations. Clear objectives and business plans should guide the selection of AI solutions, ensuring they meet organizational needs and budget considerations. Engaging both clinical and nonclinical stakeholders can help secure necessary resources, foster trust, and ensure the long-term sustainability of AI implementations. Testing, validation, training, and ongoing monitoring are pivotal for successful integration. For neurologists, safeguarding patient data privacy is paramount. Seeking guidance from institutional information technology resources for informed, compliant decisions, and remaining vigilant against biases in LLM outputs are essential practices in responsible and unbiased utilization of AI tools. In research, obtaining institutional review board approval is crucial when dealing with patient data, even if deidentified, to ensure ethical use. Compliance with established guidelines like SPIRIT-AI, MI-CLAIM, and CONSORT-AI is necessary to maintain consistency and mitigate biases in AI research. In summary, the integration of LLMs into clinical neurology offers immense promise while presenting formidable challenges. Awareness of these considerations is vital for harnessing the potential of AI in neurologic care effectively and enhancing patient care quality and safety. The article serves as a guide for health care organizations, researchers, and neurologists navigating this transformative landscape.

Motor unit potential induced repetitive discharges (MIRDs): description of an unusual iterative discharge.

INTRODUCTION: Repetitive discharges may be recorded during nerve conduction studies (NCS) or during needle electromyography in a muscle at rest. Repetitive discharges that occur during voluntary activation and are time-locked to voluntary motor unit potentials (MUP) have not been described. METHODS: Retrospective review of motor unit potential induced repetitive discharges (MIRDs) identified in the EMG laboratory. Characteristics of each MIRD, patient demographics, other EMG findings in the same muscle, and electrophysiological diagnosis were analyzed. RESULTS: MIRDs were observed in 15 patients. The morphology and number of spikes and duration of MIRDs varied. The discharges fired at rates of 50-200 Hz. All but 2 patients had EMG findings of a chronic neurogenic disorder. CONCLUSIONS: MIRDs are rare iterative discharges time-locked to a voluntary MUP. The pathophysiology of MIRDs is unclear, but their presence may indicate a chronic neurogenic process.

Neurologic Care of Forcibly Displaced Persons: Emerging Issues in Neurology.

There is a growing number of forcibly displaced persons (FDPs) worldwide. With more than 100 million people forcibly displaced today, there is an urgent mandate to understand the neurologic care needs of this population and how neurologists and other health care workers can most effectively provide that care. In this Emerging Issues in Neurology article, we attempt to (1) define the scope of the problem of providing neurologic care to FDPs, (2) highlight commonly encountered clinical challenges related to neurologic care of FDPs, and (3) provide useful clinical information for neurologists and other clinicians who deliver care to FDPs with neurologic needs. We address the terminology of forcible displacement and how terms may differ across a person's migration journey. Common challenges encountered by FDPs with neurologic needs across settings include loss of support systems, loss of personal health information, language barriers and differing expression of symptoms, differing belief systems, epidemiologic patterns of disease unfamiliar to the clinician, and patients' fear and perceived risks of engaging with health systems. Practical approaches are shared for clinicians who encounter an FDP with a neurologic presentation. Finally, the article discusses many unmet neurologic needs of FDPs, which require significant investment. These include addressing lapses in neurologic care during displacement and understanding the effects of forcible displacement on people with chronic neurologic conditions. Future research and educational resources should focus on improving epidemiologic intelligence for neurologic conditions across geographies, developing curricula for optimizing the neurologic care of FDPs, and evaluating the most appropriate and effective uses of health technologies in humanitarian settings.

Improving Neurology Clinical Care With Natural Language Processing Tools.

The integration of natural language processing (NLP) tools into neurology workflows has the potential to significantly enhance clinical care. However, it is important to address the limitations and risks associated with integrating this new technology. Recent advances in transformer-based NLP algorithms (e.g., GPT, BERT) could augment neurology clinical care by summarizing patient health information, suggesting care options, and assisting research involving large datasets. However, these NLP platforms have potential risks including fabricated facts and data security and substantial barriers for implementation. Although these risks and barriers need to be considered, the benefits for providers, patients, and communities are substantial. With these systems achieving greater functionality and the pace of medical need increasing, integrating these tools into clinical care may prove not only beneficial but necessary. Further investigation is needed to design implementation strategies, mitigate risks, and overcome barriers.

Antiamyloid Monoclonal Antibody Therapy for Alzheimer Disease: Emerging Issues in Neurology.

With recent data demonstrating that lecanemab treatment can slow cognitive and functional decline in early symptomatic Alzheimer disease (AD), it is widely anticipated that this drug and potentially other monoclonal antibody infusions targeting ß-amyloid protein will imminently be realistic options for some patients with AD. Given that these new antiamyloid monoclonal antibodies (mAbs) are associated with nontrivial risks and burdens of treatment that are radically different from current mainstays of AD management, effectively and equitably translating their use to real-world clinical care will require systematic and practice-specific modifications to existing workflows and infrastructure. In this Emerging Issues in Neurology article, we provide practical guidance for a wide audience of neurology clinicians on logistic adaptations and decision making around emerging antiamyloid mAbs. Specifically, we briefly summarize the rationale and available evidence supporting antiamyloid mAb use in AD to facilitate appropriate communication with patients and care partners on potential benefits. We also discuss pragmatic approaches to optimizing patient selection and treatment monitoring, with a particular focus on the value of incorporating shared decision making and multidisciplinary collaboration. In addition, we review some of the recognized limitations of current knowledge and highlight areas of future evolution to guide the development of sustainable and flexible models for treatment and follow-up. As the field enters a new era with disease-modifying treatment options for AD, it will be critical for neurology practices to prepare and continually innovate to ensure optimal outcomes for patients.

Measuring Ambulatory Racial and Ethnic Neurologic Disparities With the Axon Registry.

Background and Objectives: The primary objective is to examine potential racial and ethnic (R/E) disparities in ambulatory neurology quality measures within the American Academy of Neurology Axon Registry. R/E disparities in neurologic US morbidity and mortality have been clearly documented. Despite these findings, there have been no nationwide examinations of how ambulatory neurologic care affects these negative health outcomes. Methods: This was a retrospective nonrandomized cohort study of patients in the AAN Axon Registry. The Axon Registry is a neurology-specific outpatient quality registry that collects, reports, and analyzes real-world deidentified electronic health record (EHR) data. Patients were included in the study if they contributed toward one of the selected quality measures for multiple sclerosis, epilepsy, Parkinson disease, or headache during the study period of January 1, 2019-December 31, 2019. Descriptive analyses of patient demographics were performed and then stratified by race and ethnicity. Results: There were a total of 633,672 patients included in these analyses. Separate analyses were performed for race (64% White, 8% Black, 1% Asian, and 27% unknown) and ethnicity (52% not Hispanic, 5% Hispanic, and 43% unknown). The mean age ranged from 18 to 55 years, with 61% female and 39% male. Quality measures were chosen based on completeness of R/E data and were either process or outcomes focused. Statistically significant differences were noted after controlling for multiple comparisons. Discussion: The large proportion of missing or unknown R/E data and low overall rate of performance on these quality measures made the relevance of small differences difficult to determine. This analysis demonstrates the feasibility of using the Axon Registry to assess neurologic disparities in outpatient care. More education and training are required on the accurate capture of R/E data in the EHR.

Zoster-associated mononeuropathies (ZAMs): a retrospective series.

INTRODUCTION: Zoster-associated limb paresis is an uncommon complication of herpes zoster (HZ) and one whose precise pathophysiologic mechanism is poorly understood. Occasionally, the paresis results from a zoster-associated mononeuropathy (ZAM). METHODS: Mayo Clinic records between 1996 and 2010 were reviewed for patients with ZAM whose clinical, electrophysiologic, and radiographic features were then abstracted. RESULTS: Ulnar (2), median (3), femoral (1), and sciatic (2) mononeuropathies were identified. Most patients had moderate to severe weakness in affected muscles, and most had post-herpetic neuralgia (88% at 1 month and 71% at 4 months). The minimum duration of weakness was prolonged (mean, 281.9 days; range, 45-1242 days). Nerve magnetic resonance imaging (MRI) was abnormal, demonstrating nerve enlargement (4/4 cases), T2 signal hypertintensity (2/4 cases), or enhancement (1/4 cases). CONCLUSIONS: While ZAM is an uncommon occurrence following cutaneous HZ, it is associated with significant weakness, high rates of post-herpetic neuralgia, and prolonged morbidity.

Focal and other unusual presentations of facioscapulohumeral muscular dystrophy.

INTRODUCTION: Facioscapulohumeral dystrophy (FSHD) presents classically with facial and shoulder-girdle weakness. We report focal atypical presentations of FSHD. Our aim was to identify focal/unusual phenotypes in genetically confirmed FSHD cases. METHODS: We undertook a retrospective review of an academic center database of the period from 1996 to 2011. Of 139 FSHD cases, 7 had atypical genetically confirmed disease. Clinical data were abstracted. RESULTS: Seven cases (4 men) had a mean age of 37 years at onset (range 18-63 years) and mean 43 years at diagnosis (range 20-74 years). Presenting symptoms were monomelic lower limb (n = 3) or upper limb (n = 2) atrophy, or axial weakness (n = 2). Five patients had focal weakness on examination. CK was normal to borderline high. Two patients had a relative with FSHD. Coexistent unusual features included dyspnea (n = 1), S1 radicular pain with calf atrophy (n = 2), and peripheral neuropathy (n = 1). Almost all patients had myopathic EMG changes. DNA analysis showed a D4Z4 EcoRI fragment size ranging from 20 to 37 kilobases. CONCLUSIONS: FSHD may present with focal weakness, dyspnea and myopathic EMG changes. These findings should raise the possibility of FSHD.

Paraneoplastic lower motor neuronopathy associated with Hodgkin lymphoma.

INTRODUCTION: Paraneoplastic lower motor neuronopathies have been reported rarely with Hodgkin lymphoma. METHODS: We report a case of rapidly progressive motor neuronopathy preceding the diagnosis of Hodgkin lymphoma. RESULTS: A 31-year-old woman developed subacute rapidly progressive quadriparesis. Electrodiagnostic studies revealed a severe diffuse disorder of motor neurons and their axons. Symmetric enhancement of the cauda equina motor nerve roots was notable on magnetic resonance imaging scan. Further imaging demonstrated an enlarged supraclavicular lymph node, and biopsy revealed Hodgkin lymphoma. A final diagnosis of paraneoplastic motor neuronopathy was made after investigations for alternative causes of motor neuronopathy were unrevealing. Neurological improvement was seen with combined treatment of the underlying malignancy and intravenous immunoglobulin. CONCLUSIONS: Paraneoplastic causes should be considered in the differential diagnosis of subacute motor neuronopathy, as the neurological presentation may precede cancer detection. Combinations of lymphoma treatment and immunotherapy may result in a favorable outcome.

US Health Care System in 2035: The Neurology Future Forecasting Series.

Evolution of the US health care system has been punctuated by periods of rapid change. In the coming decades there will be meaningful and potentially disruptive developments in health care delivery mechanisms, the policy environment, and the populations for whom we provide care. Neurologists will need to adapt to changing patient expectations, market dynamics, and regulatory structures to thrive in the future health care environment. This article describes a forecast of potential changes in the US health care system by 2035, an assessment of the implications for the field of neurology, and a rationale for long-term strategic planning to prepare.

Creating a New Set of Milestones for the Clinical Neurophysiology Fellowship.

INTRODUCTION: The Accreditation Council for Graduate Medical Education and the American Board of Psychiatry and Neurology first developed milestones for the clinical neurophysiology (CNP) fellowship in 2015. The milestones provide a comprehensive evaluation of the fellow's development based on six domains of competency. Here, we describe the development of a new set of milestones for CNP fellowship with level 1 as the incoming level, level 4 as the goal for graduation, and level 5 as the aspirational level that may not be achieved. METHODS: Committee members were nominated or volunteered to participate in the milestones update. Milestone development began with the creation of a shared mental model of the ideal skills and knowledge a graduating CNP fellow should attain. RESULTS: The CNP committee met virtually 7 times for a total of 14 meeting hours. Nine Patient Care and five Medical Knowledge milestones evolved from the seven Patient Care and six Medical Knowledge milestones that were in the first iteration. The committee incorporated 11 "Harmonized Milestones" into the revision and a supplemental guide was created. CONCLUSIONS: The revised Accreditation Council for Graduate Medical Education milestones for CNP fellowship contain important updates that program directors should review against their curricula to identify any gaps in learning. Program leadership should take note of two new Patient Care milestones for telemedicine and intraoperative monitoring. Clinical neurophysiology fellowships are not designed to provide level 4 competency across all milestones. The revised milestones should be viewed within the context of an individual program's goals.

Trigeminal nerve electrophysiological findings in hemifacial atrophy: A systematic literature review and retrospective chart review.

OBJECTIVE: Hemifacial atrophy (HFA) is a rare disorder characterized by progressive unilateral wasting facial soft tissue, muscle, and/or bone. Trigeminal nerve abnormalities may contribute to or result from disease pathophysiology. We aimed to gain further insights into the role of trigeminal pathophysiology along the HFA severity spectrum. METHODS: A systematic literature review was performed according to PRISMA standards. Retrospective cases of HFA from the literature and Mayo Clinic EMG database were pooled for descriptive and semi-quantitative analysis. RESULTS: Overall, 13 total HFA patients were identified through literature and database reviews. Trigeminal nerve testing was abnormal in 9/13 (69%), exclusively in moderate-severe cases. Abnormalities suggested a peripheral (7/9, 78%) or mixed central/peripheral (2/9, 22%) localization. Trigeminal nerve abnormalities were not identified in any of the 4 cases with mild disease severity. CONCLUSION: Moderate to severe cases of HFA were associated with electrophysiological trigeminal abnormalities. No abnormalities were seen in mild cases of HFA. SIGNIFICANCE: Trigeminal nerve electrophysiology may serve as a biomarker of moderate-severe disease progression, likely reflecting the consequences of progressive soft tissue atrophy.

Futures Planning at the AAN: Approach and Initial Outcome.

We describe a process of organizational strategic future forecasting, with a horizon of 2035, as implemented by the American Academy of Neurology (AAN) on behalf of its members, and as a model approach for other organizations. The participants were members of the 2018-2020 AAN Boards of Directors and Executive Team, moderated by a consultant with expertise in future forecasting. Four predetermined model scenarios of import to our field (1 "expectable," 1 "challenging," and 2 "visionary") were discussed in small groups, with alternative scenarios developed in specific domains. Common themes emerged among all scenarios: the importance of thoughtful integration of biomedical and information technology tools into neurologic practice; continued demonstration of the value of neurologic care to society; and emphasis on population management and prevention of neurologic disease. Allowing for the inherent uncertainties of predicting the future, the AAN's integration of structured forecasting into its strategic planning process has allowed the organization to prepare more effectively for change, such as the disruptions stemming from the coronavirus disease 2019 (COVID-19) pandemic. The approaches outlined here will be integrated into future AAN operations and may be implemented to a similar effect by other organizations.

Primer on the In-home Teleneurologic Examination: A COVID-19 Pandemic Imperative.

It is imperative in the coronavirus disease 2019 (COVID-19) pandemic that we serve our patients by implementing teleneurology visits for those who require neurologic advice but do not need to be seen face to face. The authors propose a thorough, practical, in-home, teleneurologic examination that can be completed without the assistance of an on-the-scene medical professional and can be tailored to the clinical question. We hope to assist trainees and practicing neurologists doing patient video visits for the first time during the COVID-19 pandemic, focusing on what can, rather than what cannot, be easily examined.