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AbstractEfforts to revise the Uniform Determination of Death Act in order to align law with medical practice have failed. Medical practice must now align with the law. People who are not dead under the law that defines death should not be declared dead. There is no compelling reason to continue the practice of declaring legally living persons to be dead. [ABSTRACT FROM AUTHOR]

Objective Background Methods Results Conclusions To apply the 2019 joint American Academy of Neurology (AAN) and American Headache Society (AHS) quality measures for headache management to a cohort of neurology resident physicians and then assess outcomes related to guideline adherence.The optimization of headache management is essential to reduce both the individual and systemic impact of these disorders. In 2014, the AAN developed 10 quality measures for evidence‐based management of patients with headache. A workgroup updated and condensed its headache quality measures in 2019, narrowing the set to six measurements, four of which would primarily focus on the management of migraine and two of which would address the management of cluster headache.This quality improvement study was conducted using a pretest‐posttest study design. A pre‐intervention survey based on retrospective analysis of five clinic notes for adherence to the measures was designed and distributed to all neurology residents (n = 32) at a large, academic tertiary referral center. The intervention included the creation of an electronic medical record template to aid residents in following the measures during clinical encounters, as well as the provision of direct feedback based on pre‐intervention results. Finally, a post‐intervention survey was distributed for completion based on notes written during the intervention period. Analysis was limited to migraine, given the low percentage of cluster headache seen in clinic.An increase in adherence was seen in three of the four migraine‐related quality measures, with the Use of Abortive Medications for Migraine and Documentation of Counseling on Modifiable Lifestyle and Chronification Factors demonstrating statistically significant improvements (75.8% to 88.0% [p = 0.013] and 83.9% to 94.0% [p = 0.029] adherence, respectively). For secondary outcomes, the increase in the utilization of appropriate diagnostic criteria (82.6% to 93.2%, p = 0.018) was significant, and the self‐assessed confidence rating for adherence to guidelines was significant (p < 0.001).This study provides evidence that the quality improvement intervention led to increased adherence to the AAN and AHS migraine‐related measures. It is anticipated that increased adherence may lead to improved patient outcomes. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review aims to provide a comprehensive overview of the diagnosis of brain death/death by neurologic criteria (BD/DNC) by emphasizing the clinical criteria established by the American Academy of Neurology (AAN) in light of their updated guidelines released in 2023. In this review, we will focus on the current implementation of ancillary tests including the catheter cerebral angiogram, nuclear scintigraphy, and transcranial Doppler, which provide support in diagnoses when clinical examination and apnea tests are inconclusive. Finally, we will also provide examples to discuss the implementation of certain imaging studies in the context of diagnosing BD/DNC. Recent Findings: Recent developments in the field of neurology have emphasized the importance of clinical criteria for diagnosing BD/DNC, with the AAN providing clear updated guidelines that include coma, apnea, and the absence of brainstem reflexes. Current ancillary tests, including the catheter cerebral angiogram, nuclear scintigraphy, and transcranial Doppler play a crucial role in confirming BD/DNC when the clinical assessment is limited. The role of commonly used imaging studies including computed tomography and magnetic resonance angiographies of the brain as well as CT/MR perfusion studies will also be discussed in the context of these new guidelines. Summary: BD/DNC represents the permanent cessation of brain functions, including the brainstem. This review article provides the historical context, clinical criteria, and pathophysiology that goes into making this diagnosis. Additionally, it explores the various ancillary tests and selected imaging studies that are currently used to diagnose BD/DNC under the newly updated AAN guidelines. Understanding the evolution of how to effectively use these diagnostic tools is crucial for healthcare professionals who encounter these BD/DNC cases in their practice. [ABSTRACT FROM AUTHOR]

Background: Although effective antiretroviral therapy (ART) has improved the life expectancy of people with HIV (PWH), the prevalence of milder forms of HIV-associated neurocognitive disorders (HAND) persist, and it is associated with systemic and neuro-inflammatory processes that could impact other organ systems. However, the complex signaling mechanisms between the bone-kidney systems and the brain in HAND remain unknown. Extracellular vesicles (EVs) play a potential role in inter-organ communication and are involved in regulating cell activity in distant tissues. In this study, we examined whether levels of EVs from bone-and kidney-related cells associate with cognitive dysfunction and explored the relationship between kidney-bone EV axis in PWH experiencing cognitive deficits. Methods: EV subtypes were characterized in plasma from 61 PWH with either cognitive impairment (CI, n = 53) or normal cognition (NC, n = 8) based on the American Academy of Neurology criteria for HIV-associated dementia (HAD, n = 11), minor cognitive motor disorder (MCMD, n = 25) or asymptomatic neurocognitive impairment (ANI, n = 17) by spectral flow cytometry. EVs were profiled with markers reflecting bone and kidney cell origin. A support vector machine learning-based model was employed for analyses of EV phenotypes to predict the cognitive dysfunction. Results: Plasma-EVs expressing osteocalcin, sclerostin, and nephrin were significantly higher in the cognitive impairment group compared to the normal cognition group. EVs bearing kidney cell markers correlated significantly with bone-derived EVs. A machine learning-based model, comprised of osteocalcin+, nephrin+, and CD24+ EVs predicted cognitive impairment in PWH on ART. Conclusion: Our study reveals that neurocognitive impairment in PWH is associated with increased levels of plasma EVs enriched with the bone markers osteocalcin and sclerostin and the kidney marker nephrin, suggesting that these EV subtypes may be novel candidate biomarkers for disease-spanning neurocognitive dysfunction. Moreover, the relationship between bone-derived EVs with kidney-derived EVs may suggest their role in mediating inter-organ crosstalk in the pathogenesis of HIV-associated cognitive impairment. [ABSTRACT FROM AUTHOR]

Objective: Artificial intelligence (AI)‐based decision support systems (DSS) are utilized in medicine but underlying decision‐making processes are usually unknown. Explainable AI (xAI) techniques provide insight into DSS, but little is known on how to design xAI for clinicians. Here we investigate the impact of various xAI techniques on a clinician's interaction with an AI‐based DSS in decision‐making tasks as compared to a general population. Methods: We conducted a randomized, blinded study in which members of the Child Neurology Society and American Academy of Neurology were compared to a general population. Participants received recommendations from a DSS via a random assignment of an xAI intervention (decision tree, crowd sourced agreement, case‐based reasoning, probability scores, counterfactual reasoning, feature importance, templated language, and no explanations). Primary outcomes included test performance and perceived explainability, trust, and social competence of the DSS. Secondary outcomes included compliance, understandability, and agreement per question. Results: We had 81 neurology participants with 284 in the general population. Decision trees were perceived as the more explainable by the medical versus general population (P < 0.01) and as more explainable than probability scores within the medical population (P < 0.001). Increasing neurology experience and perceived explainability degraded performance (P = 0.0214). Performance was not predicted by xAI method but by perceived explainability. Interpretation: xAI methods have different impacts on a medical versus general population; thus, xAI is not uniformly beneficial, and there is no one‐size‐fits‐all approach. Further user‐centered xAI research targeting clinicians and to develop personalized DSS for clinicians is needed. [ABSTRACT FROM AUTHOR]

Background and objective: Prior studies reveal that invited speaker panels, editorial boards, authors of practice guidelines, and senior authors of published articles are disproportionately male in the neurology field. We aimed to analyze a gender gap in authorship of accepted abstracts to the American Academy of Neurology annual meetings in 2020 and 2021. Design/methods: This is a cross-sectional study evaluating the proportions of female first and senior abstract authors in 2020 and 2021. Abstracts were reviewed manually (n = 3,211 in 2020; n = 2,178 in 2021). Data were collected regarding the gender of first and senior authors, subspecialties, and origin of research (USA, international, or corporate-affiliated). Then, we compared the percentages of female first and senior authors in the 2 years to assess for any short-term effects of the COVID-19 pandemic. Results: Accepted abstracts with female first and senior authors comprised 46%, 34% in 2020, and the same in 2021, without change. Female senior authors had a significantly higher proportion of female first authors than their male senior author counterparts. The analysis of subspecialties with more than 100 abstracts showed the lowest percentages of female senior authors was oncology (24.7%), sleep (25.5%), headache (28.7%), and cerebrovascular disease (29%) in 2020. Cerebrovascular disease (29%) and behavioral neurology (24.7%) had the lowest percentage of female senior authors in 2021. In the analysis of the origin of research, corporate-affiliated authors had the lowest percentages of female first (34 and 36%) and senior authors (22.6 and 27.6%). Conclusion: The gender gap in neurology was reaffirmed in regards to female senior authorship overall and in subgroups of abstracts including cerebrovascular disease, headache, behavioral neurology, sleep, oncology, and corporate-affiliated research. [ABSTRACT FROM AUTHOR]

To assess the demographic characteristics and geographic distribution of neuro-ophthalmologists practicing in the United States. A cross-sectional study. Neuro-ophthalmologists across the United States. 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 United States 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.). Neuro-ophthalmologists' demographics, and information about their medical education, postgraduate education, residency training, fellowship training, years in practice, practice environment, and geographic distribution of neuro-ophthalmologists across the United States. A total of 635 neuro-ophthalmologists (436 male, 68.7%) were identified. The 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 approximately three-quarters (429, 67.6%) completed their residency in ophthalmology, 159 (25%) had residency positions in neurology and 47 (7.4%) had residency positions in both. Approximately one-third (191, 30.0%) were trained in more than 1 fellowship, including oculoplastics (78, 12.3%) or pediatric ophthalmology (53, 8.3%). The average post-fellowship years of experience was 23.7 ± 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 female neuro-ophthalmologists (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 often are trained in more than 1 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. The author(s) have no proprietary or commercial interest in any materials discussed in this article. [ABSTRACT FROM AUTHOR]

Guidelines for brain death/death by neurologic criteria (BD/DNC) determination were revised to provide a consistent and updated approach to BD/DNC evaluation across all ages by the American Academy of Neurology, American Academy of Pediatrics, Child Neurology Society, and Society of Critical Care Medicine. This article is intended to complement the guidelines and highlight aspects relevant to the critical care community; the actual guidelines should be used to update hospital protocols and dictate clinical practice. Because BD/ DNC evaluations are conducted in the ICU, it is essential for members of the critical care community to familiarize themselves with these guidelines. The fundamental concept of BD/DNC has not changed; BD/DNC is permanent loss of function of the brain as a whole, including the brain stem, resulting in coma, brainstem areflexia, and apnea in the setting of an adequate stimulus. The BD/DNC evaluation requires a sufficient observation period to ensure there is no chance of recovery, followed by exclusion of potentially confounding conditions like hypothermia, hypotension, severe metabolic disturbances, or medication effects. Specific guidance is provided for patients who were treated with therapeutic hypothermia or medical or surgical interventions to manage intracranial hypertension. The guidelines outline a structured and meticulous neurologic examination and detail the responses consistent with BD/DNC. A protocol is provided for how to safely perform apnea testing, including modifications needed for patients on extracorporeal membrane oxygenation. Controversial issues such as consent, BD/DNC evaluation in pregnancy, preservation of neuroendocrine function, and primary posterior fossa injuries are addressed. The ultimate goal is to ensure a consistent and accurate approach to BD/DNC evaluation in patients of all ages, fostering public trust in the medical community's ability to determine death. By adhering to these guidelines, critical care clinicians can confidently navigate the challenging aspects of BD/DNC determination. [ABSTRACT FROM AUTHOR]

Diagnostic, prognostic, and therapeutic procedures for patients with prolonged disorders of consciousness (pDoCs) vary significantly across countries and clinical settings, likely due to organizational factors (e.g., research vs. non-academic hospitals), expertise and availability of resources (e.g., financial and human). Two international guidelines, one from the European Academy of Neurology (EAN) and one from the American Academy of Neurology (AAN) in collaboration with the American Congress of Rehabilitation Medicine (ACRM) and the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR), were developed to facilitate consistent practice among professionals working with this challenging patient population. While the recommendations of both guidelines agree in principle, it remains an open issue how to implement them into clinical practice in the care pathway for patients with pDoCs. We conducted an online survey to explore health professional clinical practices related to the management of patients with pDoCs, and compare said practices with selected recommendations from both the guidelines. The survey revealed that while some recommendations are being followed, others are not and/or may require more honing/specificity to enhance their clinical utility. Particular attention should be given to the implementation of a multimodal assessment of residual consciousness, to the detection and treatment of pain, and to the impact of restrictions imposed by COVID-19 pandemics on the involvement of patients' families/representatives. [ABSTRACT FROM AUTHOR]

Introduction: Current diagnostic criteria for Carpel Tunnel Syndrome (CTS) include a patient's medical history, physical exam results, and electrophysiological findings. The purpose of the study is to evaluate the diagnostic ability of nerve conduction study, ultrasonography and magnetic resonance imaging for the diagnosis of carpal tunnel syndrome with the use of clinical findings as the gold standard. Methodology: The study was conducted among 30 patients clinically diagnosed having CTS based on the criteria given by American Academy of Neurology and American Academy of Physical Medicine and Rehabilitation. All patients included in the study were underwent USG of affected wrist joint, CT scan as well MRI of the same. Results: Out of total 30 participants, 14 (46.7%) were found moderate severity followed by 11 (36.7%) were found mild severity. Only 5 (16.7%) were found severe carpel tunnel syndrome. Amongst all three investigation methods, nerve conduction study having the lowest sensitivity (83.33%). The sensitivity of the ultrasonography and MRI was 90% each. Conclusion: It is clear from this study that the sensitivity of the parameters utilized in NCS (maximum observed 83.33%) is lower than that of the median nerve cross-sectional area detected on USG (90%) and MRI (90%). The most sensitive, practical, and cost-effective metric of all those seen in the research turned out to be the median nerve cross sectional area evaluated at the wrist crease by USG. [ABSTRACT FROM AUTHOR]

First-time seizures comprise 15% to 35% of all seizure-related complaints in the emergency department (ED). Emergent neuroimaging of first-time seizure patients is recommended by both the American Academy of Neurology and American College of Emergency Physicians. However, most of these studies are over 10 years old and included both adults and children. The goal of this investigation is to determine the rate of abnormal neuroimaging in adults with first-time seizures presenting to the ED during the current era. This was a prospective observational study of patients presenting to three urban EDs with a chief complaint of seizure over 18 months. Abnormal neuroimaging findings were defined a priori and were dichotomized into acute and subacute/chronic categories. Of the 2505 patients who presented with a seizure, 242 patients (9.7%) presented with a first-time seizure. The most common etiologies for first-time seizures were drug intoxication and drug withdrawal. Of those 242 patients, 29 (11.9%) patients had abnormal findings on brain computed tomography (CT). Brain CT demonstrated an acute finding in 13 (45%) patients and a subacute/chronic finding in 16 (55%) patients. The most common abnormality overall and the most common chronic finding was ischemic changes. The most common acute findings were traumatic intracranial hemorrhage and intracranial metastases. This study demonstrated that 11.9% of first-time seizure patients presenting to the ED had abnormal findings on neuroimaging. Our findings support current recommendations to obtain emergent neuroimaging for adult patients with first-time seizures. [ABSTRACT FROM AUTHOR]

Introduction: In sub-Saharan Africa (SSA), the clinical and progressive diagnostic certainty of AIDS dementia is difficult to establish due to under-medicalization and delays in consultation and especially the diversity of etiologies of demented states. Material and methods: We carried out a retrospective study of 196 patients hospitalized for dementia syndrome between 2016 and 2021 in the neurology department of the University Hospital of Conakry. The criteria labeled in this study are those retained by the DSM-IV and the classification of the American Academy of Neurology (AAN) developed in accordance with the WHO. Results: HIV etiology was identified in patients aged 44–67 years (17 women and 19 men). The clinical picture was dominated by severe cognitive disorders, slowed ideation, memory disorders and reduced motor skills associated with personality changes. Neurological examination revealed dysphoric disorders in most patients, sphincter abnormalities in 13 cases and labio-lingual tremor in 11 cases. Diagnosis was based on positive serological tests for HIV1 antibodies (25 cases) and HIV2 antibodies (1 case) using the Elisa and Western blot techniques, and the presence of discretely hypercellular CSF. Magnetic resonance imaging contributed to the diagnosis, showing diffuse white matter abnormalities with hyper signals on T2-weighted or FLAIR sequences. Conclusion: This study shows a non-stereotype clinical picture of AIDS dementia requiring a differential diagnosis with other infectious dementias. These results are important for the therapeutic and prognostic discussion. [ABSTRACT FROM AUTHOR]

Background: It is not known how large language models, such as ChatGPT, can be applied toward the assessment of the efficacy of medications, including in the prevention of migraine, and how it might support those claims with existing medical evidence. Methods: We queried ChatGPT-3.5 on the efficacy of 47 medications for the prevention of migraine and then asked it to give citations in support of its assessment. ChatGPT's evaluations were then compared to their FDA approval status for this indication as well as the American Academy of Neurology 2012 evidence-based guidelines for the prevention of migraine. The citations ChatGPT generated for these evaluations were then assessed to see if they were real papers and if they were relevant to the query. Results: ChatGPT affirmed that the 14 medications that have either received FDA approval for prevention of migraine or AAN Grade A/B evidence were effective for migraine. Its assessments of the other 33 medications were unreliable including suggesting possible efficacy for four medications that have never been used for the prevention of migraine. Critically, only 33/115 (29%) of the papers ChatGPT cited were real, while 76/115 (66%) were "hallucinated" not real papers and 6/115 (5%) shared the names of real papers but had not real citations. Conclusion: While ChatGPT produced tailored answers on the efficacy of the queried medications, the results were unreliable and inaccurate because of the overwhelming volume of "hallucinated" articles it generated and cited. [ABSTRACT FROM AUTHOR]

Simple Summary: Symptoms such as light-headedness and fainting upon standing can have a large negative impact on the quality of life, especially for people with orthostatic hypotension (blood pressure drop upon or during standing). One treatment option suggested in the clinic is head-up tilted sleeping (HUTS), where the full body is inclined. In this paper we reviewed the available evidence for the use of HUTS. We identified 10 studies focussing on HUTS as a treatment to improve orthostatic tolerance. Unfortunately, the overall evidence was weak, mainly because of the low number of included participants. We also noticed that the studied angles differed as well as the type of measurements to evaluate HUTS. Despite this, the anecdotal evidence suggested that HUTS therapy could slightly improve low standing blood pressure and its associated symptoms. The effects were more marked if higher angles were applied. These results provide some, although weak, evidence favouring HUTS, but the clinical relevance and the tolerability need to be studied further in larger-scale trials. To systematically summarize the evidence of head-up tilt sleeping (HUTS) on orthostatic tolerance, we conducted a systematic, predefined search in PubMed, OVID Embase, Cochrane and Web of Science. We included studies assessing the effect of HUTS on orthostatic tolerance and other cardiovascular measures and rated the quality with the American Academy of Neurology risk of bias tool. We included 10 studies (n = 185) in four groups: orthostatic hypotension (OH; 6 studies, n = 103), vasovagal syncope (1 study, n = 12), nocturnal angina pectoris (1 study, n = 10) and healthy subjects (2 studies, n = 58). HUTS duration varied (1 day–4 months) with variable inclinations (5°–15°). In two of six OH studies, HUTS significantly improved standing systolic blood pressure. Orthostatic tolerance was consistently enhanced in OH studies with higher angles (≥12°), in 2 out of 3 with smaller angles (5°) but also in one studying horizontal sleeping. In vasovagal syncope, HUTS significantly augmented resilience to extreme orthostatic stress. One study was rated as a class II risk of bias, one of Class II/III and eight of Class IV. The evidence favouring HUTS to improve orthostatic tolerance is weak due to variable interventions, populations, small samples and a high risk of bias. Despite this, we found some physiological signs suggesting a beneficial effect. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a common neurodevelopmental condition. The American Academy of Paediatrics and American Academy of Neurology do not recommend routine brain magnetic resonance imaging (MRI) in the assessment of ASD. The need for a brain MRI should be decided on atypical features in the clinical history and examination. However, many physicians continue to use brain MRI routinely in the assessment process. We performed a retrospective review of indications for requesting brain MRI in our institution over a 5-year period. The aim was to identify the yield of MRI in children with ASD and calculate the prevalence of significant neuroimaging abnormalities in children with ASD and identify clinical indications for neuroimaging. One hundred eighty-one participants were analysed. An abnormal brain MRI was identified in 7.2% (13/181). Abnormal brain MRI was more likely with an abnormal neurological examination (OR 33.1, p = 0.001) or genetic/metabolic abnormality (OR 20, p = 0.02). In contrast, abnormal MRI was not shown to be more likely in children with a variety of other indications such as behavioural issues and developmental delay. Conclusion: Thus, our findings support that MRI should not be a routine investigation in ASD, without additional findings. The decision to arrange brain MRI should be made on a case-by-case basis following careful evaluation of potential risks and benefits. The impact of any findings on the management course of the child should be considered prior to arranging imaging. What is Known: • Incidental brain MRI findings are common in children with and without ASD. • Many children with ASD undergo brain MRI in the absence of neurological comorbidities. What is New: • Brain MRI abnormalities in ASD are more likely with an abnormal neurological examination and genetic or metabolic conditions. • Prevalence of significant brain MRI abnormalities in ASD alone is low. [ABSTRACT FROM AUTHOR]

Introduction: Eight members of the International Parkinson's Disease and Movement Disorders Society Tic and Tourette Syndrome Study Group formed a subcommittee to discuss further barriers to practice guideline implementation. Based on expert opinion and literature review, the consensus was that practice variations continue to be quite broad and that many barriers in different clinical settings might negatively influence the adoption of the American Academy of Neurology and the European Society for the Study of Tourette Syndrome published guidelines. Objectives: 1) To identify how clinical practices diverge from the existing American Academy of Neurology and European Society for the Study of Tourette Syndrome guidelines, and 2) to identify categories of barriers leading to these clinical care gaps. Methods and analysis: This article presents the methodology of a planned cross-sectional survey amongst healthcare professionals routinely involved in the clinical care of patients with persistent tic disorders, aimed at 1) identifying how practices diverge from the published guidelines; and 2) identifying categories of barriers leading to these clinical care gaps. Purposeful sampling methods are used to identify and recruit critical persistent tic disorders stakeholders. The analysis will use descriptive statistics. [ABSTRACT FROM AUTHOR]

Deoxycytidine/deoxythymidine combination therapy safety and efficacy in treatment of POLG-related disorders: results after 6 months of treatment. The 75th Annual Meeting of the American Academy of Neurology (AAN) was held in Boston (MA, USA) in April 2023. Dr. Myers presented 6-month treatment data for eight participants with POLG-related disorders from the ongoing 2-year, open-label, single-centre study. The VISIONARY-MS study was a phase II, randomised, double-blind, placebo-controlled trial in stable relapsing-remitting MS patients with chronic optic neuropathy who were treated with other disease-modifying therapies (DMTs) [[4]]. [Extracted from the article]

Painful diabetic peripheral neuropathy (PDPN) is present in nearly a quarter of people with diabetes. It is estimated to affect over 100 million people worldwide. PDPN is associated with impaired daily functioning, depression, sleep disturbance, financial instability, and a decreased quality of life. Despite its high prevalence and significant health burden, it remains an underdiagnosed and undertreated condition. PDPN is a complex pain phenomenon with the experience of pain associated with and exacerbated by poor sleep and low mood. A holistic approach to patient-centred care alongside the pharmacological therapy is required to maximise benefit. A key treatment challenge is managing patient expectation, as a good outcome from treatment is defined as a reduction in pain of 30– 50%, with a complete pain-free outcome being rare. The future for the treatment of PDPN holds promise, despite a 20-year void in the licensing of new analgesic agents for neuropathic pain. There are over 50 new molecular entities reaching clinical development and several demonstrating benefit in early-stage clinical trials. We review the current approaches to its diagnosis, the tools, and questionnaires available to clinicians, international guidance on PDPN management, and existing pharmacological and non-pharmacological treatment options. We synthesise evidence and the guidance from the American Association of Clinical Endocrinology, American Academy of Neurology, American Diabetes Association, Diabetes Canada, German Diabetes Association, and the International Diabetes Federation into a practical guide to the treatment of PDPN and highlight the need for future research into mechanistic-based treatments in order to prioritise the development of personalised medicine. [ABSTRACT FROM AUTHOR]

Mild traumatic brain injury (mTBI) is a major public health concern. Cerebrovascular alterations play a significant role in the evolution of injury sequelae and in the process of post-traumatic brain repair. Arterial spin labeling (ASL) is an advanced perfusion magnetic resonance imaging technique that permits noninvasive quantification of cerebral blood flow (CBF). This is the first systematic review of ASL research findings in patients with mTBI. Our approach followed the American Academy of Neurology (AAN) and PRISMA guidelines. We searched Ovid/MEDLINE, Web of Science, Scopus, and the Cochrane Index for relevant articles published as of February 20, 2020. Full-text results were combined into Rayyan software for further evaluation. Data extraction, including risk of bias ratings, was performed using American Academy of Neurology's four-tiered classification scheme. Twenty-three articles met inclusion criteria comprising data on up to 566 mTBI patients and 654 control subjects. Of the 23 studies, 18 reported some type of regional CBF abnormality in mTBI patients at rest or during a cognitive task, with more findings of decreased than increased CBF. The evidence supports the conclusion that mTBI likely causes ASL-derived CBF anomalies. However, synthesis of findings was challenging due to substantial methodological variations across studies and few studies with low risk of bias. Thus, larger-scale prospective cohort studies are needed to more definitively chart the course of CBF changes in humans after mTBI and to understand how individual difference factors contribute to post-injury CBF changes. [ABSTRACT FROM AUTHOR]

Background: There is increasing interest in therapeutic ketosis as a potential therapy for neurodegenerative disorders--in particular, mild cognitive impairment (MCI), Alzheimer's disease (AD), and Parkinson's disease (PD)--following a proof-of-concept study in Parkinson's disease published in 2005. Methods: To provide an objective assessment of emerging clinical evidence and targeted recommendations for future research, we reviewed clinical trials involving ketogenic interventions in mild cognitive impairment, Alzheimer's disease, and Parkinson's disease reported since 2005. Levels of clinical evidence were systematically reviewed using the American Academy of Neurology criteria for rating therapeutic trials. Results: 10 AD, 3 MCI, and 5 PD therapeutic ketogenic trials were identified. Respective grades of clinical evidence were objectively assessed using the American Academy of Neurology criteria for rating therapeutic trials. We found class "B" evidence (probably effective) for cognitive improvement in subjects with mild cognitive impairment and subjects with mild-to-moderate Alzheimer's disease negative for the apolipoprotein ε4 allele (APOε4-). We found class "U" evidence (unproven) for cognitive stabilization in individuals withmild-to-moderate Alzheimer's disease positive for the apolipoprotein ε4 allele (APOε4+). We found class "C" evidence (possibly effective) for improvement of non-motor features and class "U" evidence (unproven) for motor features in individuals with Parkinson's disease. The number of trials in Parkinson's disease is very small with best evidence that acute supplementation holds promise for improving exercise endurance. Conclusions: Limitations of the literature to date include the range of ketogenic interventions currently assessed in the literature (i.e., primarily diet or medium-chain triglyceride interventions), with fewer studies using more potent formulations (e.g., exogenous ketone esters). Collectively, the strongest evidence to date exists for cognitive improvement in individuals with mild cognitive impairment and in individuals withmild-to-moderate Alzheimer's disease negative for the apolipoprotein ε4 allele. Larger-scale, pivotal trials are justified in these populations. Further research is required to optimize the utilization of ketogenic interventions in differing clinical contexts and to better characterize the response to therapeutic ketosis in patients who are positive for the apolipoprotein ε4 allele, as modified interventions may be necessary. [ABSTRACT FROM AUTHOR]