Impact of Stroke Call on the Stroke Neurology Workforce in the United States: Possible Challenges and Opportunities.

BACKGROUND: The Stroke & Vascular Neurology Section of the American Academy of Neurology was charged to identify challenges to the recruitment and retention of stroke neurologists and to make recommendations to address any identified problems. The Section initiated this effort by determining the impact of stroke on-call requirements as a barrier to the recruitment and retention of vascular neurologists. METHODS: This is a cross-sectional survey of a sample of US Neurologists providing acute stroke care. RESULTS: Of the 900 neurologists who were sent surveys, 313 (35%) responded. Of respondents from institutions providing stroke coverage, 71% indicated that general neurologists and 45% indicated that vascular neurologists provided that service. Of those taking stroke call, 36% agreed with the statement, "I spent too much time on stroke call," a perception that was less common among those who took less than 12-hour shifts (P < .0001); 21% who participated in stroke call were dissatisfied with their current job. Forty-six percent indicated that their stroke call duties contributed to their personal feeling of "burnout." CONCLUSIONS: Although the reasons are likely multifactorial, our survey of neurologists providing stroke care suggests that over-burdensome on-call responsibilities may be contributing to the vascular neurology workforce burnout and could be affecting recruitment and retention of vascular neurologists. Strategies to reduce the lifestyle impact of stroke call may help address this problem.

Tumefactive demyelination presenting during bevacizumab treatment.

We report the emergence of tumefactive demyelination during treatment with intravitreal bevacizumab (Avastin). This is of particular significance given that bevacizumab is currently being assessed as a potential treatment option for neuromyelitis optica, another demyelinating condition.

Supply and demand analysis of the current and future US neurology workforce.

OBJECTIVE: This study estimates current and projects future neurologist supply and demand under alternative scenarios nationally and by state from 2012 through 2025. METHODS: A microsimulation supply model simulates likely career choices of individual neurologists, taking into account the number of new neurologists trained each year and changing demographics of the neurology workforce. A microsimulation demand model simulates utilization of neurology services for each individual in a representative sample of the population in each state and for the United States as a whole. Demand projections reflect increased prevalence of neurologic conditions associated with population growth and aging, and expanded coverage under health care reform. RESULTS: The estimated active supply of 16,366 neurologists in 2012 is projected to increase to 18,060 by 2025. Long wait times for patients to see a neurologist, difficulty hiring new neurologists, and large numbers of neurologists who do not accept new Medicaid patients are consistent with a current national shortfall of neurologists. Demand for neurologists is projected to increase from ∼18,180 in 2012 (11% shortfall) to 21,440 by 2025 (19% shortfall). This includes an increased demand of 520 full-time equivalent neurologists starting in 2014 from expanded medical insurance coverage associated with the Patient Protection and Affordable Care Act. CONCLUSIONS: In the absence of efforts to increase the number of neurology professionals and retain the existing workforce, current national and geographic shortfalls of neurologists are likely to worsen, exacerbating long wait times and reducing access to care for Medicaid beneficiaries. Current geographic differences in adequacy of supply likely will persist into the future.

Capturing incentives and avoiding penalties: The carrot and the stick.

Over the past decade, health care in the United States has been a topic of intense political debate, resulting in dramatic legislative, regulatory, and economic changes. These changes have occurred due to the unsustainable rise of health care costs without accompanying improvement in measured health outcomes when compared to other economically developed countries. In an attempt to contain costs and improve the quality of health care provided, the Center for Medicare and Medicaid Services has implemented 4 distinct incentive-based programs. Data are scarce concerning whether such programs will be successful in accomplishing these goals. Each health care provider will need to weigh the costs of participation against the fines incurred by nonparticipation (up to 10% of annual Medicare payments). Knowledge of the percentage of one's practice dedicated to the care of patients in the Medicare and Medicaid programs will be helpful in arriving at a final decision.

The use of physical restraints in neurologic patients in the inpatient setting.

Neurologists are commonly asked to make decisions concerning the use of physical restraints on hospitalized patients. These decisions are determined within the context of medical risk to the patient, including falls and the disruption of medical therapies (eg, self-extubation, removal of nasogastric tubes), risk to the caregivers, and the wishes of patients and their families. Familiarity with the medicolegal issues involved, including regulations of the local hospital and governmental agencies, as well as current evidence concerning the efficacy and harms that can occur with these interventions, is paramount to determining whether to use devices designed to restrict patients' freedom of movement in order to control their behavior.

A novel phenotype for the dynein heavy chain mutation Loa: altered dendritic morphology, organelle density, and reduced numbers of trigeminal motoneurons.

Dynein, the retrograde motor protein, is essential for the transport of cargo along axons and proximal dendrites in neurons. The dynein heavy chain mutation Loa has been reported to cause degeneration of spinal motor neurons, as well as defects of spinal sensory proprioceptive neurons, but cranial nerve nuclei have received little attention. Here, we examined the number and morphology of neurons in cranial nerve nuclei of young, adult, and aged heterozygous Loa mice, with a focus on the trigeminal, facial, and trochlear motor nuclei, as well as the proprioceptive mesencephalic trigeminal nucleus. By using stereological counting techniques, we report a slowly progressive and significant reduction, to 75% of wild-type controls, in the number of large trigeminal motoneurons, whereas normal numbers were found for sensory mesencephalic trigeminal, facial, and trochlear motoneurons. The morphology of many surviving large trigeminal motoneurons was substantially altered, in particular the size and length of perpendicularly extending primary dendrites, but not those of facial or trochlear motoneurons. At the ultrastructural level, proximal dendrites of large trigeminal motoneurons, but not other neurons, were significantly depleted in organelle content such as polyribosomes and showed abnormal (vesiculated) mitochondria. These data indicate primary defects in trigeminal α-motoneurons more than γ-motoneurons. Our findings expand the Loa heterozygote phenotype in two important ways: we reveal dendritic in addition to axonal defects or abnormalities, and we identify the Loa mutation as a mouse model for mixed motor-sensory loss when the entire neuraxis is considered, rather than a model primarily for sensory loss.

How does the genetic assassin select its neuronal target?

Through many different routes of analysis, including human familial studies and animal models, we are identifying an increasing number of genes that are causative for human neurodegenerative disease and are now in a position for many such disorders to dissect the molecular pathology that gives rise to neuronal death. Yet a paradox remains: The majority of the genes identified cause neurodegeneration in specific neuronal subtypes, but the genes themselves are ubiquitously expressed. Furthermore, the different mutations in the same gene may cause quite different types of neurodegeneration. Something in our understanding of neurodegenerative disease is clearly missing, and we refer to this as the phenomenon of "neuronal targeting." Here we discuss possible explanations for neuronal targeting, why specific neuronal subtypes are vulnerable to specific mutations in ubiquitously expressed genes.

PRNP allelic series from 19 years of prion protein gene sequencing at the MRC Prion Unit.

Mutation of the human prion protein gene (PRNP) open reading frame (ORF) accounts for almost all reported familial concurrence of prion disease. The more common mutations globally: octapeptide repeat insertions, P102L, D178N, E200K, and V210I have occurred in large multigenerational pedigrees and display autosomal dominant inheritance, however, many rare genetic changes have been reported that are of uncertain pathogenicity. Based on 19 years of PRNP sequencing at the MRC Prion Unit, London, and analysis of 3664 samples from patients referred with suspected prion disease and healthy populations, we present novel allele combinations, healthy control population data, results of screening the PRNP ORF in DNA from the entire referral series and the CEPH human genome diversity cell line panel. Of the 10 alleles detected in patients for which detailed cases histories are presented, 4 are unreported (G54S, D167N, V209M, Q212PP), two changes are thought to be pathogenic but have not been described in our regions (P105L from the UK, G114V from India and Turkey), and the remainder reported in healthy control populations or in trans to known pathogenic mutations suggesting non- or low pathogenicity (G54S, 1-OPRI, G142S, N171S, V209M, E219K). New genotype-phenotype correlations and population frequencies presented will help the diagnosis and genetic counselling of those with suspected inherited prion disease.

Modification of superoxide dismutase 1 (SOD1) properties by a GFP tag--implications for research into amyotrophic lateral sclerosis (ALS).

BACKGROUND: Since the discovery that mutations in the enzyme SOD1 are causative in human amyotrophic lateral sclerosis (ALS), many strategies have been employed to elucidate the toxic properties of this ubiquitously expressed mutant protein, including the generation of GFP-SOD1 chimaeric proteins for studies in protein localization by direct visualization using fluorescence microscopy. However, little is known about the biochemical and physical properties of these chimaeric proteins, and whether they behave similarly to their untagged SOD1 counterparts. METHODOLOGY/PRINCIPAL FINDINGS: Here we compare the physicochemical properties of SOD1 and the effects of GFP-tagging on its intracellular behaviour. Immunostaining demonstrated that SOD1 alone and GFP-SOD1 have an indistinguishable intracellular distribution in PC12 cells. Cultured primary motor neurons expressing GFP or GFP-SOD1 showed identical patterns of cytoplasmic expression and of movement within the axon. However, GFP tagging of SOD1 was found to alter some of the intrinsic properties of SOD1, including stability and specific activity. Evaluation of wildtype and mutant SOD1, tagged at either the N- or C-terminus with GFP, in PC12 cells demonstrated that some chimaeric proteins were degraded to the individual proteins, SOD1 and GFP. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that most, but not all, properties of SOD1 remain the same with a GFP tag.

Pay for performance and the physicians quality reporting initiative in neurologic practice.

Pay-for-performance (P4P) initiatives are receiving significant attention in the media and throughout all parts of health care. To improve quality, hundreds of private payers have initiated P4P programs over the past decade. Recently, the federal government has followed suit with its Physicians Quality Reporting Initiative (PQRI). These programs have several potential shortcomings, and questions arise as to their value in truly improving health outcomes. Nevertheless, momentum continues to gather in both the public and private sectors for P4P to serve as a catalyst for health care reform.

13C NMR of polyolefins with a new high temperature 10 mm cryoprobe.

Recently, a high temperature 10 mm cryoprobe was developed. This probe provides a significant sensitivity enhancement for (13)C NMR of polyolefins at a sample temperature of 120-135 degrees C, as compared to conventional probes. This greatly increases the speed of NMR studies of comonomer content, sequence distribution, stereo- and regioerrors, saturated chain end, unsaturation, and diffusion of polymers. In this contribution, we first compare the (13)C NMR sensitivity of this probe with conventional probes. Then, we demonstrate one of the advantages of this probe in its ability to perform 2D Incredible Natural Abundance Double Quantum Transfer Experiment (2D INADEQUATE) in a relatively short period of time. The 2D INADEQUATE has been rarely used for polymer studies because of its inherently very low sensitivity. It becomes even more challenging for studying infrequent polyolefin microstructures, as low probability microstructures represent a small fraction of carbons in the sample. Here, the 2D INADEQUATE experiment was used to assign the (13)C NMR peaks of 2,1-insertion regioerrors in a poly(propylene-co-1-octene) copolymer.

Intra- and intermolecular NMR studies on the activation of arylcyclometallated hafnium pyridyl-amido olefin polymerization precatalysts.

Pyridyl-amido catalysts have emerged recently with great promise for olefin polymerization. Insights into the activation chemistry are presented in an initial attempt to understand the polymerization mechanisms of these important catalysts. The activation of C1-symmetric arylcyclometallated hafnium pyridyl-amido precatalysts, denoted Me2Hf{N(-),N,C(-)} (1, aryl = naphthyl; 2, aryl = phenyl), with both Lewis (B(C6F5)3 and [CPh3][B(C6F5)4]) and Brønsted ([HNR3][B(C6F5)4]) acids is investigated. Reactions of 1 with B(C6F5)3 lead to abstraction of a methyl group and formation of a single inner-sphere diastereoisomeric ion pair [MeHf{N(-),N,C(-)}][MeB(C6F5)3] (3). A 1:1 mixture of the two possible outer-sphere diastereoisomeric ion pairs [MeHf{N(-),N,C(-)}][B(C6F5)4] (4) is obtained when [CPh3][B(C6F5)4] is used. [HNR3][B(C6F5)4] selectively protonates the aryl arm of the tridentate ligand in both precatalysts 1 and 2. A remarkably stable [Me2Hf{N(-),N,C2}][B(C6F5)4] (5) outer-sphere ion pair is formed when the naphthyl substituent is present. The stability is attributed to a hafnium/eta(2)-naphthyl interaction and the release of an eclipsing H-H interaction between naphthyl and pyridine moieties, as evidenced through extensive NMR studies, X-ray single crystal investigation and DFT calculations. When the aryl substituent is phenyl, [Me2Hf{N(-),N,C2}][B(C6F5)4] (10) is originally obtained from protonation of 2, but this species rapidly undergoes remetalation, methane evolution, and amine coordination, giving a diastereomeric mixture of [MeHf{N(-),N,C(-)}NR3][B(C6F5)4] (11). This species transforms over time into the trianionic-ligated [Hf{N(-),C(-),N,C(-)}NR3][B(C6F5)4] (12) through activation of a C-H bond of an amido-isopropyl group. In contrast, ion pair 5 does not spontaneously undergo remetalation of the naphthyl moiety; it reacts with NMe2Ph leading to [MeHf{N(-),N}NMe2C6H4][B(C6F5)4] (7) through ortho-metalation of the aniline. Ion pair 7 successively undergoes a complex transformation ultimately leading to [Hf{N(-),C(-),N,C(-)}NMe2Ph][B(C6F5)4] (8), strictly analogous to 12. The reaction of 5 with aliphatic amines leads to the formation of a single diastereomeric ion pair [MeHf{N(-),N,C(-)}NR3][B(C6F5)4] (9). These differences in activation chemistry are manifested in the polymerization characteristics of these different precatalyst/cocatalyst combinations. Relatively long induction times are observed for propene polymerizations with the naphthyl precatalyst 1 activated with [HNMe3Ph][B(C6F5)4]. However, no induction time is present when 1 is activated with Lewis acids. Similarly, precatalyst 2 shows no induction period with either Lewis or Brønsted acids. Correlation of the solution behavior of these ion pairs and the polymerization characteristics of these various species provides a basis for an initial picture of the polymerization mechanism of these important catalyst systems.

Quiet mutations in inbred strains of mice.

The year 2009 is the 100th anniversary of the founding of the first inbred strain of mouse, called DBA. During the last 100 years, inbred strains have proved their value for biomedical research and the number of such strains has mushroomed to over 450, each with different genotypic and phenotypic characteristics and useful for the study of disease and normal function. However, although inbred strains are stable, they are not fixed entities and researchers need to be aware of the phenomena of new mutations and of genetic drift, which occur within all mouse colonies. If the mutations are what we term in this review 'quiet mutations', then they might result in rather unexpected and sometimes tremendously valuable results. Here, we discuss these phenomena and look at how new genomic technologies might help us to detect 'quiet mutations' and use them to our advantage.

Practice Advisory: utility of surgical decompression for treatment of diabetic neuropathy: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

Surgical decompression at the site of anatomic narrowing has been promoted as an alternative treatment for patients with symptomatic diabetic neuropathy. Systematic review of the literature revealed only Class IV studies concerning the utility of this therapeutic approach. Given the current evidence available, this treatment alternative should be considered unproven (Level U). Prospective randomized controlled trials with standard definitions and outcome measures are necessary to determine the value of this therapeutic intervention.

Supportive care for patients with Guillain-Barré syndrome.

A multidisciplinary consensus group searched MEDLINE from 1966 to May 2003, extracted relevant references, and prepared recommendations on supportive care for Guillain-Barré syndrome. In the absence of randomized controlled trials, we agreed on recommendations by consensus based on observational studies and expert opinion. In the acute phase in bed-bound adult patients, the group recommended the use of heparin and graduated pressure stockings to prevent deep vein thrombosis, monitoring for blood pressure, pulse, autonomic disturbances, and respiratory failure, and the timely institution of artificial ventilation and tracheostomy. Pain management is difficult, but carbamazepine or gabapentin may help. The cautious use of narcotic analgesics may be needed. Disabled patients should be treated by a multidisciplinary rehabilitation team and should receive an assistive exercise program. Persistent fatigue following Guillain-Barré syndrome is common and may be helped by an exercise program. Because of a very small and possibly only theoretical increase in the risk of recurrence following immunization, the need for immunization should be reviewed on an individual basis. More research is needed to identify optimal methods for all aspects of supportive care.