Search

It is unknown if patients with neuromuscular diseases prefer in-person or virtual telemedicine visits. We studied patient opinions and preference on virtual versus in-person visits, and the factors influencing such preferences.Telephone surveys, consisting of 11 questions, of patients from 10 neuromuscular centers were completed.Five hundred and twenty surveys were completed. Twenty-six percent of respondents preferred virtual visits, while 50% preferred in-person visits. Sixty-four percent reported physical interaction as "very important." For receiving a new diagnosis, 55% preferred in-person vs 35% reporting no preference. Forty percent were concerned about a lack of physical examination vs 20% who were concerned about evaluating vital signs. Eighty four percent reported virtual visits were sufficiently private. Sixty eight percent did not consider expenses a factor in their preference. Although 92% were comfortable with virtual communication technology, 55% preferred video communications, and 19% preferred phone calls. Visit preference was not significantly associated with gender, diagnosis, disease severity, or symptom management. Patients who were concerned about a lack of physical exam or assessment of vitals had significantly higher odds of selecting in-person visits than no preference.Although neither technology, privacy, nor finance burdened patients in our study, more patients preferred in-person visits than virtual visits and 40% were concerned about a lack of physical examination. Interactions that occur with in-person encounters had high importance for patients, reflecting differences in the perception of the patient-physician relationship between virtual and in-person visits.

There is a growing need for brief screening measures for HIV Associated Neurocognitive Disorders (HAND). We compared two commonly used measures (the Montreal Cognitive Assessment [MoCA] and the International HIV Dementia Scale [IHDS]) in their ability to identify asymptomatic HAND (i.e., asymptomatic neurocognitive impairment [ANI]). Participants included 74 Thai PLWH: 38 met Frascati criteria for ANI and 36 were cognitively normal (CN). Participants completed Thai language versions of the MoCA (MoCA-T) and IHDS, and a validated neurocognitive battery. We examined between-group differences for MoCA-T and IHDS total scores, and scale subcomponents. We also conducted receiver operating characteristic (ROC) analyses to determine the ability of the MoCA-T and IHDS to discriminate between CN and ANI groups, and compared their area under the curve (AUC) values. Results revealed lower MoCA-T total score, as well as the Visuospatial/Executive and Delayed Recall subtask scores, in the ANI relative to CN group. Groups did not differ on the IHDS. For ROC analyses, the MoCA-T, but not the IHDS, significantly differentiated the ANI from CN group, and there was a significant difference in AUC values between the MoCA-T (AUC = .71) and IHDS (AUC = .56). Sensitivity and specificity statistics were poor for both screening measures. These data indicate while the MoCA-T functions better than the IHDS in detecting Thai PLWH with ANI, the mildest form of HAND, neither cognitive screener, showed strong utility. Our findings reflect the limited efficacy of common screening measures in detecting subtler cognitive deficits among Thai PLWH, and highlight the need for better screening tools.

Mismatch between whole-brain death criteria embedded in statutes and accepted tests physicians use to diagnose brain death have clinical and ethical implications that could undermine public trust in death pronouncements. We consider merits and drawbacks of 4 ways to address this problem.

Background and ObjectivesPeripheral nerve impairments and dementia are common among older adults and share risk factors. However, few studies have examined whether peripheral nerve function and dementia are associated. We evaluated whether lower extremity peripheral nerve impairments were associated with higher incidence of dementia and whether associations differed by comorbidity subgroups (diabetes, low vitamin B12, and APOE ε4 allele carriers).MethodsWe studied Black and White Health, Aging, and Body Composition Study participants 70 to 79 years of age and without dementia at enrollment. Lower extremity sensory and motor peripheral nerve function was measured at year 4 (the analytic baseline of this study). Sensory nerve impairments were measured with monofilament (1.4 g, 10 g) and vibration threshold of the toe. Monofilament insensitivity was defined as unable to detect monofilament (3 of 4 touches), and vibration detection impairment was defined as >130 μm. Fibular motor impairments were defined as ResultsAmong 2,174 participants (52% women, 35% Black), 45% could not detect monofilament 1.4 g, 9% could not detect monofilament 10 g, 6% could not feel vibration, 10% had low CMAP amplitude, and 24% had slow conduction velocity. Monofilament 10 g (hazard ratio [HR] 1.35, 95% CI 0.99–1.84) and vibration detection insensitivity (HR 1.73, 95% CI 1.24–2.40) were associated/borderline associated with a higher risk of dementia after covariate adjustment. Estimates were elevated but not significant for monofilament 1.4 g, CMAP amplitude, and conduction velocity (p > 0.05). Increasing number of peripheral nerve impairments was associated with higher risk of dementia in a graded fashion; for ≥3 impairments, the HR was 2.37 (95% CI 1.29–4.38). In subgroup analyses, effect estimates were generally higher among those with diabetes, low vitamin B12, and APOE ε4 allele except for vibration detection.DiscussionPeripheral nerve impairments, especially sensory, were associated with a higher risk of dementia even after adjustment for age and other health factors. These associations may represent a shared susceptibility to nervous system degeneration.

Black people living in the United States suffer disproportionate morbidity and mortality across a wide range of neurologic conditions. Despite common conceptions to the contrary, “race” is a socially defined construct with little genetic validity. Therefore, racial health inequities in neurology (“neurodisparities”) are not a consequence of biologic differences between races. Instead, racism and associated social determinants of health are the root of neurodisparities. To date, many neurologists have neglected racism as a root cause of neurologic disease, further perpetuating the problem. Structural racism, largely ignored in current neurologic practice and policy, drives neurodisparities through mediators such as excessive poverty, inferior health insurance, and poorer access to neurologic and preventative care. Interpersonal racism (implicit or explicit) and associated discriminatory practices in neurologic research, workforce advancement, and medical education also exacerbate neurodisparities. Neurologists cannot fulfill their professional and ethical responsibility to care for Black patients without understanding how racism, not biologic race, drives neurodisparities. In our review of race, racism, and race-based disparities in neurology, we highlight the current literature on neurodisparities across a wide range of neurologic conditions and focus on racism as the root cause. We discuss why all neurologists are ethically and professionally obligated to actively promote measures to counteract racism. We conclude with a call for actions that should be implemented by individual neurologists and professional neurologic organizations to mitigate racism and work towards health equity in neurology.

OBJECTIVES HIV-associated neurocognitive disorders (HAND) remain prevalent in people living with HIV (PLWH) despite widespread use of combined antiretroviral therapy (ART). Vascular disease contributes to the pathogenesis of HAND, but traditional vascular risk factors do not fully explain the relation between vascular disease and HAND. A more direct measure of vascular dysfunction is needed. This cross-sectional study tested whether the cardio-ankle vascular index (CAVI), a novel method to assess arterial stiffness, is associated with HAND among PLWH. METHODS Participants included 75 non-diabetic adults with well-controlled HIV from an outpatient HIV clinic. We assessed the relation between CAVI and neurocognitive impairment (NCI). The latter was primarily characterized by the Frascati criteria and secondarily (post hoc) using the Global Deficit Score (GDS). Logistic regression models tested whether high CAVI (≥ 8) was independently associated with NCI when controlling for potential confounders. RESULTS Participants (Mage = 45.6 ± 8.3 years; 30.1% male) had few traditional cardiovascular disease (CVD) risk factors (hypertension, n = 7; dyslipidaemia, n = 34; body mass index ≥ 25 kg/m2 , n = 12; smoking history, n = 13; 2.2% mean 10-year risk of CVD or stroke). Twelve (16%) participants had high CAVI, which was independently associated with meeting Frascati criteria for NCI [n = 39, odds ratio (OR) = 7.6, p = 0.04], accounting for age, education, gender, income, CD4 nadir, recent CD4 and traditional CVD risk factors. High CAVI was also associated with NCI as reflected by higher GDS (OR = 17.4, p = 0.02). CONCLUSIONS Cardio-ankle vascular index is a promising measure of vascular dysfunction that may be independently associated with NCI in relatively healthy PLWH. Larger studies should test the utility of CAVI in predicting NCI/decline in PLWH.

Some causes of spastic paraplegia are treatable and many are not. Diagnostic work-up to determine the etiology can be costly and invasive. Here we report the case of a man with slowly progressive spastic paraparesis. Using a multigene next-generation sequencing (NGS) panel, we identified a novel variant in the consensus splice site of the SPAST gene (exon 13, c.1536G>A, heterozygous), affecting codon 512 of the SPAST mRNA. The observed variant segregated with the disease in four tested family members. In this case, genetic confirmation obviated the need for additional testing such as MRI and lumbar puncture and helped the patient and his family understand his condition and prognosis. We conclude with a brief discussion of the SPG4/SPAST gene and the role of multigene panels in the diagnosis and management of hereditary spastic paraplegia.

ObjectiveTo detail the scope and nature of financial conflicts of interest (COIs) between neurologists and the pharmaceutical and medical device industries (Industry) using the Centers for Medicare and Medicaid Services Open Payments (OP) database, with a focus on trends from 2013 to 2016.MethodsPayments from Industry to US neurologists were categorized into research payments, general (nonresearch) payments, and value of ownership in Industry. We performed descriptive analyses to detail the scope and nature of these relationships and trends over time.ResultsAt least 9,505 neurologists received at least one payment from Industry each year. From 2013 to 2016, 1.6 million payments totaled $354 million, of which 99.5% of payments and 85.6% of payment value were for general/nonresearch-related payments. Most neurologists (between 65% and 80%) received less than $1,000 per year, but over 200 neurologists each received more than $100,000 during some years. Several received over $1 million. General payments are increasing, research payments are steady, and neurologists' ownership and investments are decreasing.ConclusionsNeurologists have extensive financial relationships with Industry, though this is driven by a well-paid minority. As a profession, we must work to establish firm rules to manage these potential COIs, ensuring that relationships with Industry yield synergistic advances while minimizing bias and maintaining public trust.

There is a growing need for brief screening measures for HIV Associated Neurocognitive Disorders (HAND). We compared two commonly used measures (the Montreal Cognitive Assessment [MoCA] and the International HIV Dementia Scale [IHDS]) in their ability to identify asymptomatic HAND (i.e., asymptomatic neurocognitive impairment [ANI]). Participants included 74 Thai PLWH: 38 met Frascati criteria for ANI and 36 were cognitively normal (CN). Participants completed Thai language versions of the MoCA (MoCA-T) and IHDS, and a validated neurocognitive battery. We examined between-group differences for MoCA-T and IHDS total scores, and scale subcomponents. We also conducted receiver operating characteristic (ROC) analyses to determine the ability of the MoCA-T and IHDS to discriminate between CN and ANI groups, and compared their area under the curve (AUC) values. Results revealed lower MoCA-T total score, as well as the Visuospatial/Executive and Delayed Recall subtask scores, in the ANI relative to CN group. Groups did not differ on the IHDS. For ROC analyses, the MoCA-T, but not the IHDS, significantly differentiated the ANI from CN group, and there was a significant difference in AUC values between the MoCA-T (AUC = .71) and IHDS (AUC = .56). Sensitivity and specificity statistics were poor for both screening measures. These data indicate while the MoCA-T functions better than the IHDS in detecting Thai PLWH with ANI, the mildest form of HAND, neither cognitive screener, showed strong utility. Our findings reflect the limited efficacy of common screening measures in detecting subtler cognitive deficits among Thai PLWH, and highlight the need for better screening tools.

ObjectiveTo detail the scope, nature, and disclosure of financial conflicts of interest (COI) between the pharmaceutical and medical device industries (Industry) and authors in high-impact clinical neurology journals.MethodsUsing the Centers for Medicare and Medicaid Services Open Payments Database (OPD), we retrieved information on payments from Industry to 2,000 authors from randomly selected 2016 articles in 5 journals. We categorized payments by type (research, general, and associated research/institutional), sponsoring entity, and year (from 2013 to 2016). Each author's self-disclosures were compared to OPD-listed Industry relationships to measure discordance. Payments were manually reviewed to identify those from manufacturers of products that were directly tested or discussed in the article. We also quantified the prevalence and value of these nondisclosed, relevant COI.ResultsTwo hundred authors from 158 articles had at least 1 OPD payment. Median/mean annual payments per author were $4,229/$19,586 (general); $1,702/$5,966 (research); and $67,512/$362,102 (associated research). Most neurologists received 10% of authors) received more than $10,000 per year, and several received over $1 million. Of 3,013 payments deemed directly relevant to the article, 50.9% were not self-disclosed by the authors, totaling $5,782,197 ($1,665,603 general; $25,532 research; $4,091,062 associated research).ConclusionIndustry-related financial relationships are prevalent among United States–based physicians publishing in major neurology journals, and incomplete self-disclosure is common. As a profession, academic and other neurologists must work to establish firm rules to ensure and manage disclosure of financial COI.

Organ donation after the circulatory determination of death (DCDD) accounts for a growing percentage of deceased organ donations. Although hospital DCDD protocols stipulate donor death determination, some do not adhere to national guidelines that require mechanical, not electrical, asystole. Surrogate decisions to withdraw life-sustaining therapy should be separated from decisions to donate organs. Donor families should be given sufficient information about the DCDD protocol and its impact on the dying process to provide informed consent, and donors should be given proper palliative care during dying. An unresolved ethical question is whether and how donor consent should be seen as authorizing manipulation of a living donor during the dying process solely for to benefit of the organ recipient.

Brain death has been accepted as a legal definition of death in most countries, but practices for determining brain death vary widely. One source of variation is in the use of ancillary tests to assist in the diagnosis of brain death. Through case-based discussions with 3 experts from 3 continents, this article discusses selected aspects of brain death, with a focus on the use of ancillary tests. In particular, we explore the following questions: Are ancillary tests necessary, or is the clinical examination sufficient? What ancillary tests are preferred, and under which circumstances? Are ancillary tests required when the primary mechanism of injury is brainstem injury? Should the family's wishes play a role in the need for ancillary tests? The same case-based questions were posed to the rest of our readership in an online survey, the preliminary results of which are also presented.

Background Minorities have historically been underrepresented in clinical research trials despite having comparatively poor health indicators. Recognizing the dual inequalities of increased disease burden and decreased research participation, the National Institute of Health (NIH) Revitalization Act of 1993 mandated the inclusion and reporting of women and minorities in NIH-funded research. While progress has been made in the subsequent decades, this underrepresentation of minorities in research trials persists and has been documented in multiple disciplines. However, the extent of adequate representation and reporting of minority inclusion in clinical trials for migraine remains unknown. Objectives In this systematic review and study, we review the literature examining the representation of women and minorities in migraine clinical research trials Methods First we searched PubMed for pertinent articles examining the inclusion of women and minorities in migraine clinical research trials. Second, we identified controlled-trials for migraine published since 2011 in major neurology, headache, and general medicine journals using the terms “migraine randomized controlled trial.” We then reviewed the results manually and excluded pilot studies and those with fewer than 50 participants. We next determined (a) how frequently representation of minorities and women were reported in these major trials; (b) what factors correlated with reporting; and (c) whether women and minority inclusion comprised their ratios in the general population. Results We identified 128 relevant clinical trials, of which 36 met our inclusion criteria. All 36 trials (100%) reported gender frequency, and 25 of 36 (69.4%) reported ethnicity or race. Among all studies, women and Whites represented 84.2 and 82.9% of participants (mean), respectively. Studies conducted in the United States and funded by a private company were more likely to report race than studies conducted exclusively outside of the U.S. or with a public sponsor. No studies stratified efficacy or safety by ethnicity or gender. Men and non-Whites in the U.S. were statistically underrepresented. Conclusions Most recent headache studies comply with the NIH mandate to include women and minorities in research trials, particularly U.S.-based and industry-funded studies. Whites are overrepresented compared to both the general population and the population of migraineurs. Future studies should strive to increase minority participation and investigate race-based differences in migraine expression, treatment response, and medication toxicity.

To detail the scope and nature of financial conflicts of interest (COIs) between neurologists and the pharmaceutical and medical device industries (Industry) using the Centers for Medicare and Medicaid Services Open Payments (OP) database, with a focus on trends from 2013 to 2016.Payments from Industry to US neurologists were categorized into research payments, general (nonresearch) payments, and value of ownership in Industry. We performed descriptive analyses to detail the scope and nature of these relationships and trends over time.At least 9,505 neurologists received at least one payment from Industry each year. From 2013 to 2016, 1.6 million payments totaled $354 million, of which 99.5% of payments and 85.6% of payment value were for general/nonresearch-related payments. Most neurologists (between 65% and 80%) received less than $1,000 per year, but over 200 neurologists each received more than $100,000 during some years. Several received over $1 million. General payments are increasing, research payments are steady, and neurologists' ownership and investments are decreasing.Neurologists have extensive financial relationships with Industry, though this is driven by a well-paid minority. As a profession, we must work to establish firm rules to manage these potential COIs, ensuring that relationships with Industry yield synergistic advances while minimizing bias and maintaining public trust.

Drs. Ahlawat and Narayanaswami1 detailed the extent of industry-related financial interests among neurologists captured in the Open Payments (OP) database. Industry-related conflicts of interests (COIs) widely influence neurologic education, research, and clinical practice.2 Industry-funded trials often reach different conclusions than non-industry-funded trials,3 and even small gifts to physicians can influence their prescribing practices.4 Despite the OP database's shortcomings,5 it is an important step for 2 reasons. First, disclosure only mitigates COI if the disclosed information is widely and publicly available. Patients are generally not aware of their doctors' financial relationships.6 We hope OP will improve transparency. Second, the resulting social pressure from this transparency could lead to divestment from financial COI. Full disclosure is an important step towards mitigating COI, but does not redress subconscious biases that nearly invariably accompany financial relationships2; COI avoidance is often preferable. To investigate OP's effects on divestiture, we reviewed all neurologists in OP from 2013 to 2016. Of 9,505 neurologists in 2013 (OP's first year), 13 (0.07%) had ownership or investment interests totaling $26,610,645 (mean $2,800; median $65,975; maximum $24,949,811. In 2016, 16 of 11,105 neurologists had ownership and investment interest (0.09%) totaling $2,103,947 (mean $191; median $41,497; maximum $700,521). Perhaps OP is having an effect, but more research is required.

Objectives To compare outcomes between two models of acute ischemic stroke care. Namely 1) “drip-and-stay”, i.e. IV tissue plasminogen activator (tPA) administered at a spoke hospital in a telestroke network, with the patient remaining at the spoke, versus 2) “drip-and-ship”, i.e. tPA administered at a spoke hospital with subsequent patient transfer to a hub hospital, and 3) “hub”, i.e. tPA and subsequent treatment at a hub hospital. Materials and Methods We performed a systematic review and meta-analysis according to PRISMA guidelines. Literature searches of MEDLINE, Embase, and Cochrane from inception-October 2019 included randomized control trials and observational cohort studies comparing the drip-and-stay model to hub and drip-and-ship models. Outcomes of interest were functional independence (modified Rankin Scale ≤ 1), symptomatic intracranial hemorrhage (sICH), mortality, and length of stay. Pooled effect estimates were calculated using a fixed-effects meta-analysis and random-effects Bayesian meta-analysis. Non-inferiority was calculated using a fixed-margin method. Results Of 2806 unique records identified, 10 studies, totaling 4,164 patients, fulfilled the eligibility criteria. Meta-analysis found no significant difference in functional outcomes (mRS0-1) (6 studies, RR=1.09, 95%CI 0.98–1.22, p=0.123), sICH (8 studies, RR=0.98, 95%CI 0.64–1.51, p=0.942), or 90-day mortality (5 studies, RR=0.98, 95%CI 0.73–1.32, p=0.911, respectively) between patients treated in a drip-and-stay model compared to patients treated in drip-and-ship or hub models. There was no significant heterogeneity in these outcomes. Drip-and-stay outcomes (mRS 0–1, sICH) were non-inferior when compared to the combined group. Conclusions Our findings indicate that drip-and-stay is non-inferior to current models of drip-and-ship or hub stroke care, and may be as safe and as effective as either.

Objective: To determine the safety of domperidone in the treatment of nausea associated with dihydroergotamine (DHE) infusion and headache. Methods: We audited our use of domperidone for the inpatient management of nausea, focusing on known safety concerns, particularly potential cardiac arrhythmias. Results: We reviewed 103 consecutive admissions of 90 patients admitted for IV DHE by infusion. Most admissions were to treat chronic migraine with (n = 53) or without (n = 46) aura. Domperidone was administered in 85 of 103 encounters and was well-tolerated at doses up to 80 mg/d. A significant side effect, akathisia, was observed in one patient. Baseline ECG with corrected QT interval (QTc) was obtained on all patients. Repeat ECG after domperidone was obtained in 21 patients, whose baseline characteristics did not differ from the group as a whole. ECG was interpreted blindly by a cardiac electrophysiologist. QTc did not differ before and after domperidone administration (Wilcoxon signed-rank test, median [interquartile range] 435.0 [410.5–453.0] at admission and 427.0 [399.0–452.5] after domperidone; p = 0.15). In combination with other antiemetics, domperidone was effective in treating nausea such that no patients had refractory nausea severe enough to limit DHE dose. Conclusions: This retrospective audit demonstrates that domperidone is safe in the treatment of nausea associated with inpatient DHE infusion and headache. While larger prospective trials are necessary to confirm these results and assess efficacy, current evidence and clinical experience suggests that domperidone is safe and useful for nausea and headache management. Classification of evidence: This study provides Class IV evidence that for patients with headache undergoing DHE infusion, domperidone is safe and effective in the treatment of nausea.

Magnetic resonance neurography (MRN) is an important tool to detect abnormalities of peripheral nerves. This pictorial review demonstrates the MRN features of a variety of neuropathies affecting the lumbosacral plexus (LSP) and lower extremity nerves, drawn from over 1200 MRNs from our institution and supplemented by the literature. Abnormalities can be due to spinal compression, extraspinal compression, malignancy, musculoskeletal disease, iatrogenesis, inflammation, infection, and idiopathic disorders. We discuss indications and limitations of MRN in diagnosing LSP neuropathies. As MRN becomes more widely used, physicians must become familiar with the differential diagnosis of abnormalities detectable with MRN of the LSP.

Psychogenic nonepileptic seizures (PNES) are relatively common, accounting for 5-40% of visits to tertiary epilepsy centers. Inpatient video-electroencephalogram (vEEG) monitoring is the gold standard for diagnosis, but additional positive predictive tools are necessary given vEEG's relatively scarce availability. In this study, we investigated if the number of patient-reported allergies distinguishes between PNES and epilepsy. Excessive allergy-reporting, like PNES, may reflect somatization. Using electronic medical records, ICD-9 codes, and text-identification algorithms to search EEG reports, we identified 905 cases of confirmed PNES and 5187 controls with epilepsy but no PNES. Patients with PNES averaged more self-reported allergies than patients with epilepsy alone (1.93 vs. 1.00, p

A conflict of interest (COI) exists when a physician's professional responsibilities are compromised by personal or financial relationships. COIs between physicians and the pharmaceutical or medical device industry (Industry) are common. Collaborations with Industry have many potential benefits, but also raise potential ethical pitfalls. Industry-related COIs have widespread influence on medical education, research, and clinical practice, and therefore have profound implications for the integrity of the field of medicine. Full disclosure is an important step toward mitigating COI but does not redress subconscious accompanying biases. I review the spectrum of potential COI faced by physicians, with a focus on the ethics surrounding the relationship between neurologists and Industry. Other financial and nonfinancial COIs that influence neurologists and nonindividual entities, such as academic institutions, medical journals, and professional societies, are also discussed. Solutions ranging from disclosure to avoidance and recusal are briefly considered.

I read with interest Llinas et al.1's article that discussed burnout and resiliency. I appreciate the authors' emphasis on the primacy of systemic changes to address the problem, such as increasing opportunities for recognition and rewarding activities.

In the article “BOLD cerebrovascular reactivity as a novel marker for crossed cerebellar diaschisis,” Sebok et al. reported similar sensitivity of blood oxygen level–dependent cerebrovascular reactivity (BOLD-CVR) in detecting crossed cerebellar diaschisis (CCD) as compared to (15O)-H2O-PET in 25 participants with symptomatic unilateral cerebrovascular steno-occlusive disease and reported that those with CCD had poorer baseline neurologic performance and 3-month neurologic outcome. In response, Reidler et al. question whether CCD was the cause of consequence of poor outcomes, noting that it may be an epiphenomenon of large-volume supratentorial strokes and citing conflicting evidence in the literature about independent association of CCD with post-stroke outcomes. They suggest accounting for lesion volume and distribution in the analyses. In their reply, Niftrik et al. agree that their finding of worse outcome in those with CCD should be cautiously interpreted and investigated in follow-up studies, but argue that supratentorial stroke volume is an inexact measurement, although stroke location would be helpful to examine. They clarify their finding of impaired supratentorial BOLD-CVR in the group with CCD and opine that hemodynamic changes may cause CCD rather than just functional disruption.

Dementia is a common condition that impacts the patient, the family, and society. Currently, a diagnosis of dementia evokes hopelessness in the afflicted, and society provides few resources or systematic support for caregivers or for demented patients. In this commentary, we discuss the origins of hopelessness in dementia, the World Health Organization's six-stage framework of dementia care, and barriers to "normalizing" the experience of dementia in order to provide beneficent and humane care for patients with dementia. We also offer recommendations for clinicians who care for patients who feel that a life with dementia is not worth living.

Reduced delivery of glucose and oxygen during brain ischemia can cause energy failure (ATP depletion), which can in turn trigger processes leading to cell death. Glucose can support glycolytic ATP production even in the absence of oxygen, and it would seem to follow that increased glucose in the residual blood flow to ischemic brain should increase cell survival. This was tested experimentally in a rat model of ischemia/reperfusion by Pulsinelli et al1 several decades ago. Glucose had a striking effect, but in the direction opposite to what might be expected: rats in which circulating blood glucose was increased by intravenous infusion had far more extensive brain injury and mortality compared with normoglycemic rats. This experiment has subsequently been revisited dozens of times, using different animal species, stroke models, glucose concentrations, timing of glucose elevations, and permutations of these factors. The net result is one of the most robust in all of stroke research: hyperglycemia almost always exacerbates brain injury.2,3 Clinical experience mirrors the animal literature in these respects, because both retrospective studies and patient registries show a striking correlation between elevated admission glucose concentrations and poor outcomes.4 Hyperglycemia is similarly associated with increased hemorrhage formation and poor outcome in patients treated with tissue plasminogen activator.5–7 Random blood glucose levels are ≈4.4 to 6.1 mmol/L in both humans and rodents, with rodents being the species most commonly used for experimental stroke. The definition of hyperglycemia varies somewhat in stroke studies, ranging from 6.1 to >10 mmol/L glucose. Using these definitions, hyperglycemia is found at presentation in 30% to 60% of all patients with stroke.8,9 Some of these patients are diabetic, but acute, poststroke hyperglycemia is a sympathomimetic stress response in most. Despite the frequency of hyperglycemia in stroke and >30 …

I applaud the Brain Death Working Group for working toward uniform standards for determination of brain death.1

Facial neuropathy is most commonly seen as an idiopathic unilateral palsy known as Bell’s palsy. Generally, acute onset of typical lower motor neuron facial weakness that is not associated with other atypical or suspicious features, remains unilateral, and recovers completely requires no further workup. A recurrent or bilateral peripheral facial palsy makes an idiopathic cause less likely and prompts a more in-depth workup. The appropriate work-up of unilateral or bilateral facial palsy guided by the presence or absence of associated clinical findings is discussed. The major differentials for bilateral facial paresis include brainstem (especially pontine and prepontine) tumors, Lyme disease (especially in endemic areas), basal menigitides, Guillain-Barre syndrome, and sarcoidosis.

Peripheral Nerve and Muscle Disease uses a case-based approach to cover common and important topics in the diagnosis and treatment of neuromuscular disorders. Neuromuscular cases are always challenging. This is because even with nerve conduction studies and electromyography diagnostic certainty can still be difficult. Even with recent advances in serologic and genetic testing diagnostic certainty may be elusive. Each chapter provides an overview of the approach to the problem in question followed by a discussion of the diagnosis, key points to remember, and selected references for further reading. For this edition, new cases include Lambert-Eaton syndrome, botulism, facioscapulohumeral muscular dystrophy, and several types of neuropathy. Peripheral Nerve and Muscle Disease is an engaging collection of thought-provoking cases that clinicians can use when they encounter difficult patients on the ward or in the clinic. The volume is also a self-assessment tool that tests the reader’s ability to answer the question “What do I do now?”

A number of nutritional causes of peripheral neuropathy have been identified. Patients who have gastrointestinal disease or who have undergone bariatric surgery are at risk, although frequently the specific cause is not ascertained. Vitamin B12 and thiamine deficiencies are the most common causes in bariatric surgery patients. The classic clinical picture of Vitamin B12 deficiency is a myelopathy with a concomitant peripheral neuropathy. Thiamine deficiency is the classic triad of mental status changes, opthalmoplegia, and ataxia. Copper deficiency is often unrecognized. Its presentation can be similar to Vitamin B12 deficiency. It is important that bariatric surgery patients receive continual follow up of their nutritional status and adherence to vitamin supplementation. Alcohol may cause a peripheral neuropathy through nutritional deficiency or perhaps direct toxic effects. Other deficiency states are discussed.

Multifocal motor neuropathy (MMN) may be mistaken for common entrapment neuropathies, although absence of significant sensory findings is a helpful clue to the diagnosis. Multifocal motor neuropathy may also mimic motor neuron disease. Electrophysiological evidence of conduction block at a nerve site not typically prone to compression is consistent with MMN. A positive anti-GM1 antibody also supports the diagnosis. First-line treatment of MMN is intravenous immunoglobulin (IVIG), and the majority of patients have rapid improvement of their weakness. The clinical features, differential diagnosis, investigations, and treatment options are described in this chapter.

An infant presenting with acute weakness is an alarming problem that requires urgent diagnosis and action. Acute inflammatory demyelinating polyradiculoneuropathy is always a consideration, but botulism is important to remember. We discuss the key clinical signs that distinguish botulism from other causes of acute weakness, including pupillary and gastrointestinal dysfunction. We review the various forms of botulism and the known epidemiology. Botulism-related neuromuscular junction pathophysiology is reviewed. We discuss treatment and stress that supportive modalities and BIG-IV should be instituted early. We discuss prognosis and reinforce that despite the condition's seriousness, prognosis is good with prompt recognition and treatment.

The sudden onset of leg weakness and pain may be mistaken for an acute lumbosacral radiculopathy due to a herniated disc. However, in diabetics it is also essential to consider the entity of Bruns-Farland syndrome, or diabetic lumbosacral plexopathy (DLSP). DLSP is uncommon compared with lumbosacral radiculopathy, so delays in diagnosis are the rule rather than the exception. In this chapter we present the clinical characteristics of DLSP and the key features that can help with making a prompt diagnosis. The use of nerve conduction studies and EMG for confirmation of DLSP is reviewed. Treatment options and controversies are discussed.

A patient presents with a sensorimotor neuropathy and believes he has been poisoned. The approach to the differential diagnosis of arsenic toxicity is presented. Comparisons with mimics of this entity are made, and clinical clues to its early detection are provided. There are typical skin and nail changes with can occur with arsenic poisoning. Arsenic poisoning can appear similar to Guillain-Barre syndrome with gastrointestinal symptoms and later an ascending paralysis. Urine arsenic levels are more reliable than blood levels. Hair and nail samples are very useful in confirming the diagnosis. Electrodiagnostic testing confirmed an axonal polyneuropathy. Treatment of arsenic poisoning is discussed. The recent lead contamination in Flint Michigan points out that heavy metal poisoning still occurs despite public health awareness.

Guillain-Barré syndrome may present in several ways, although predominant proximal weakness is a common feature of the disease to recognize. The differential diagnosis may be extensive and can include infection, vasculitis, toxin exposure, and malignancy. A lumbar puncture must be done with minimal delay to evaluate for cerebrospinal fluid (CSF) albuminocytological dissociation, however results may be normal early in the course of the disease. EMG/NCS are helpful to support the diagnosis, and early treatment with intravenous immunoglobulin (IVIG) is essential. This chapter discusses the clinical features and diagnostic considerations of this important condition.

Distal, symmetric polyneuropathy can occur in a number of conditions including in association with HIV infection. The most common neurologic complication of HIV infection is a painful, distal sensory polyneuropathy (HIV-DSP). Other neuromuscular manifestations of HIV are myriad especially in the setting of fluctuating immunocompetence and the potential impact of neurotoxic medications. In the patient described in the case, peroneal neuropathy as the cause for foot drop is suggested by ankle dorsiflexion and eversion weakness with preservation of inversion and knee flexion strength. Mononeuropathy in the setting of HIV should prompt consideration of vasculitic, lymphomatous, and infectious causes, some of which can manifest with systemic findings. A rare neuromuscular complication of HIV-infected patients with sicca symptoms suggestive of Sjogren’s syndrome is diffuse infiltrative lymphocytosis syndrome. This syndrome can manifest as an acute or subacute painful sensory polyneuropathy but also as a mononeuropathy multiplex. This is discussed in the chapter.

Neurogenic thoracic outlet syndrome (NTOS) is an uncommon cause of chronic arm pain and numbness but should not be missed. It can lead to chronic pain and disability. Symptoms of NTOS are often aggravated by arm exertion and elevation and tend to occur after exercise rather than activity. A thorough diagnostic evaluation is key, which includes provocative tests, imaging, electromyography/nerve conduction study, and diagnostic injections. Electromyography/nerve conduction study (EMG/NCS) are recommended for NTOS as it is important to exclude an entrapment neuropathy or cervical radiculopathy that may be misdiagnosed as NTOS. EMG/NCS is usually normal in NTOS, however, in severe presentations, the EMG/NCS pattern is most consistent with a lower trunk plexopathy. Treatment options of NTOS are also described in this chapter.

Chemotherapy-induced peripheral neuropathy is a common complication of cancer therapy. The diagnosis is generally straightforward, based on the temporal association of symptoms with the offending agent. However, it can sometimes take on a different form of severe, fulminant neuropathy and must be differentiated from other neurologic conditions that occur in the setting of cancer. Particular care must be taken in the patient with clinical indicators of longstanding, hereditary neuropathy as these can confer a distinctive susceptibility to neurotoxicity. The diagnosis relies on an index of suspicion and the exclusion of mimics of toxic neuropathy. The most important and common agents responsible for toxic neuropathy and their range of effects on nerve are discussed.

Sciatic neuropathy presents with buttock pain worsened by sitting on the affected side and associated with ankle and knee extension weakness. Electrodiagnostic evaluation will help to distinguish it from peroneal or tibial mononeuropathies, lumbosacral plexopathy, or lumbosacral radiculopathy. It can be difficult to distinguish from a peroneal mononeuropathy due to the preferential involvement of the peroneal division of the sciatic nerve. EMG study of the short head of the biceps femoris allows for distinction between these entities. Long-term outcome and prognosis studies are sparse although Preservation of distal lower-extremity strength may be a significant predictor earlier and/or better clinical recovery.

Lambert-Eaton myasthenic syndrome (LEMS) can be a difficult condition to diagnose. In this chapter, the clinical picture and characteristics are discussed. The pathophysiology is also reviewed. Features to distinguish LEMS from more common neuromuscular junction conditions such as myasthenia gravis are reviewed. We review features that distinguish between idiopathic and paraneoplastic forms, and we discuss the importance of tumor surveillance. Antibody testing and the correct electrodiagnostic strategy are presented. Treatment of LEMS is outlined.Lambert-Eaton syndrome (LES) is a difficult condition to diagnose. The unique clinical picture and its characteristics are discussed. This is especially true in the patient without a diagnois of cancer. Antibody testing and the correct electrodiagnostic strategy are presented. Treatment of LES is outlined.

Severe shoulder pain in the absence of a clear orthopedic cause may be due to acute brachial plexitis. Numbness and tingling in association with weakness and muscle atrophy that cannot be accounted for by a single nerve or nerve root distribution suggests the diagnosis. Additional clues suggesting brachial plexitis include intensity of shoulder pain and antecedent events such as illness, vaccination, injury, unusual physical activity or surgery. The approach to diagnosis of plexitis/plexopathy and appropriate evaluation for etiology are discussed. Management of this condition is conservative, relating to pain control and judicious use of mobilization and strengthening with physical therapy. Prognosis is generally good with recovery of strength occurring in weeks to months.

Hereditary neuropathies are common. They are often diagnosed when another medical issue begins, for example, orthopedic foot problems or chemotherapy that causes a persistent severe neuropathy. Our patient developed a peroneal neuropathy after a long international airline flight. Initially it was thought to be related to lumbosacral radiculopathy. Careful history, neurological examination, and electrodiagnostic testing was helpful in pointing to a peroneal neuropathy rather than a lumbosacral radiculopathy. Family history in evaluating patients with peripheral neuropathy is essential. The actual examination and testing of relatives may be necessary. Genetic testing for the confirmation of the diagnosis of hereditary neuropathy is outlined. Clinical features of the most common hereditary peripheral are listed. It is important to recognize that a patient has a hereditary neuropathy before therapy with a chemotherapeutic agent is initiated.

Treatment issues are discussed in the setting of a very challenging patient with amyotrophic lateral sclerosis with frontotemporal dementia (FTD), including management of neurological symptoms and cognitive dysfunction. Features of FTD are discussed. It is now appreciated that FTD is more common than previously thought. FTD can occur before the onset of motor symptoms. An ALS multidisciplinary clinic is the best approach for the care of ALS patients. Ethical issues are analyzed in this case as well. The need for the discussion of end of life issues is important for the patient family and caregivers. The careful consideration of tracheostomy and ventilator use is important in light of pulmonary function. Pulmonary function testing and sleep studies are helpful in managing respiratory issues. Palliative care consultation can be very beneficial.

Paraproteinemic demyelinating peripheral neuropathies require specific diagnostic and management approaches. The clinical features as well as the type of monoclonal protein and possible associated antibodies are all important considerations in evaluation and management of these complex presentations. It is important to recognize anti-myelin associated glycoproteins positive peripheral neuropathy, which is associated with IgM gammopathy, and typically presents with a sensory ataxia. Hematologic disease may mimic chronic inflammatory demyelinating polyneuropathy. This chapter also describes the role of hematological evaluation for patients with peripheral neuropathy and a monoclonal gammopathy.

Facioscapulohumeral muscular dystrophy (FSHD) is the third most common muscular dystrophy, following Duchenne muscular dystrophy and myotonic dystrophy. The clinical secerity is extremely variable, with symptom onset anywhere from infancy to middle adulthood. The cardinal clinical features of facioscapulohumeral muscular dystrophy include facial weakness and scapular winging. Other important examination findings including scalloping of the trapezius, “Popeye” forearms, horizontal axillary folds, and a positive Beevor’s sign. It can rarely present as a pattern of weakness mimicking limb-girdle muscular dystrophy with approximately 20% of patients eventually requiring a wheelchair for ambulation. Creatine kinase is normal or mildly elevated. Genetic testing for the D4Z4 repeat contraction on chromosome 4q35 detects 95% of cases but may not reflect severity of the disease.

Neuromuscular disorders are important causes of newly acquired weakness in the intensive care unit. Although evaluation usually begins with physical examination findings, these can be compromised in the intensive care unit environment. Therefore, electrodiagnostic study becomes even more important as a tool in localizing weakness to nerve, muscle or neuromuscular junction. Critical illness neuropathy and myopathy occurs in the setting of sepsis and multiple organ failure where sepsis is accompanied by the systemic inflammatory response syndrome. Additional, intensive care unit-specific risk factors exist, predominantly relating to administration of high-dose steroids, nondepolarizing neuromuscular blocking agents, and sedating agents such as propofol. There is no specific treatment except for optimizing medical management of the underlying disorder, including prevention and management of sepsis, systemic inflammatory response syndrome, and organ damage, as well as avoidance of exacerbating medications.

Small-fiber neuropathy typically presents with burning pain or with widespread brief stabbing pains, by atypical presentations including asymmetric sensory symptoms are common. Nerve conduction studies are usually normal, as this disorder test only interrogates large fiber function; in small-fiber neuropathy the pathology is restricted to smaller unmyelinated fibers. Autonomic neuropathy can accompany the painful peripheral neuropathy but can be difficult to recognize since the symptoms can be protean. In this chapter, clinical characteristics of small-fiber and autonomic neuropathy are discussed. Various diagnostic modalities are described, including the benefits and pitfalls of available options. The most common conditions causing small-fiber and autonomic neuropathy are reviewed. The controversy surrounding impaired glucose tolerance as an etiological factor is dicusssed. We discuss the available medications and outline a rational approach to treatment.