James C. Stevens

Practice parameter: immunotherapy for Guillain-Barré syndrome: report of the Quality Standards Subcommittee of the American Academy of Neurology.

Objective: To provide an evidence-based statement to guide physicians in the management of Guillain–Barré syndrome (GBS). Methods: Literature search and derivation of evidence-based statements concerning the use of immunotherapy were performed. Results: Treatment with plasma exchange (PE) or IV immunoglobulin (IVIg) hastens recovery from GBS. Combining the two treatments is not beneficial. Steroid treatment given alone is not beneficial. Recommendations: 1) PE is recommended for nonambulant adult patients with GBS who seek treatment within 4 weeks of the onset of neuropathic symptoms. PE should also be considered for ambulant patients examined within 2 weeks of the onset of neuropathic symptoms; 2) IVIg is recommended for nonambulant adult patients with GBS within 2 or possibly 4 weeks of the onset of neuropathic symptoms. The effects of PE and IVIg are equivalent; 3) Corticosteroids are not recommended for the management of GBS; 4) Sequential treatment with PE followed by IVIg, or immunoabsorption followed by IVIg is not recommended for patients with GBS; and 5) PE and IVIg are treatment options for children with severe GBS.

Intravenous immunoglobulin for treatment of mild-to-moderate Alzheimer's disease: a phase 2, randomised, double-blind, placebo-controlled, dose-finding trial

BACKGROUND Three small trials suggest that intravenous immunoglobulin can affect biomarkers and symptoms of mild-to-moderate Alzheimers disease. We tested the safety, effective dose, and infusion interval of intravenous immunoglobulin in such patients. METHODS We did a multicentre, placebo-controlled phase 2 trial at seven sites in the USA and five in Germany. Participants with probable Alzheimers disease aged 50-85 years were randomly assigned (by a computer-generated randomisation sequence, with block sizes of eight) to infusions every 4 weeks (0·2, 0·5, or 0·8 g intravenous immunoglobulin per kg bodyweight, or placebo) or infusions every 2 weeks (0·1, 0·25, or 0·4 g/kg, or placebo). Patients, caregivers, investigators assessing outcomes, and staff at imaging facilities and the clinical research organisation were masked to treatment allocation, but dispensing pharmacists, the statistician, and the person responsible for final PET analyses were not. Treatment was masked with opaque pouches and infusion lines. The primary endpoint was median area under the curve (AUC) of plasma amyloid β (Aβ)(1-40) between the last infusion and the final visit (2 weeks or 4 weeks depending on infusion interval) in the intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT00812565) and controlled-trials.com (ISRCTN64846759). FINDINGS 89 patients were assessed for eligibility, of whom 58 were enrolled and 55 included in the primary analysis. Median AUC of plasma Aβ(1-40) was not significantly different for intravenous immunoglobulin compared with placebo for five of the six intervention groups (-18·0 [range -1347·0 to 1068·5] for 0·2 g/kg, -364·3 [-5834·5 to 1953·5] for 0·5 g/kg, and -351·8 [-1084·0 to 936·5] for 0·8 g/kg every 4 weeks vs -116·3 [-1379·0 to 5266·0] for placebo; and -13·8 [-1729·0 to 307·0] for 0·1 g/kg, and -32·5 [-1102·5 to 451·5] for 0·25 g/kg every 2 weeks vs 159·5 [51·5 to 303·0] for placebo; p>0·05 for all). The difference in median AUC of plasma Aβ(1-40) between the 0·4 g/kg every 2 weeks group (47·0 [range -341·0 to 72·5]) and the placebo group was significant (p=0·0216). 25 of 42 (60%) patients in the intervention group versus nine of 14 (64%) receiving placebo had an adverse event. Four of 42 (10%) patients in the intravenous immunoglobulin group versus four of 14 (29%) receiving placebo had a serious adverse event, including one stroke in the intervention group. INTERPRETATION Intravenous immunoglobulin may have an acceptable safety profile. Our results did not accord with those from previous studies. Longer trials with greater power are needed to assess the cognitive and functional effects of intravenous immunoglobulin in patients with Alzheimers disease.

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.

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.

Multiple sclerosis: magnetic resonance imaging, evoked responses, and spinal fluid electrophoresis.

Magnetic resonance images (MRI), evoked responses (ER), and CSF findings were compared in 39 patients with possible, probable, or definite MS. MRI disclosed multiple lesions (72%) more often than ERs (55%) in the total group of patients. In possible MS, MRI showed multiple lesions in 71%, and ER abnormalities were found in 41%. MRI is the preferred test for patients with suspected MS, but ERs are useful when MRI is normal and in the evaluation of optic nerve or spinal cord lesions.

Practice guideline update summary: Mild cognitive impairment: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology

Objective To update the 2001 American Academy of Neurology (AAN) guideline on mild cognitive impairment (MCI). Methods The guideline panel systematically reviewed MCI prevalence, prognosis, and treatment articles according to AAN evidence classification criteria, and based recommendations on evidence and modified Delphi consensus. Results MCI prevalence was 6.7% for ages 60–64, 8.4% for 65–69, 10.1% for 70–74, 14.8% for 75–79, and 25.2% for 80–84. Cumulative dementia incidence was 14.9% in individuals with MCI older than age 65 years followed for 2 years. No high-quality evidence exists to support pharmacologic treatments for MCI. In patients with MCI, exercise training (6 months) is likely to improve cognitive measures and cognitive training may improve cognitive measures. Major recommendations Clinicians should assess for MCI with validated tools in appropriate scenarios (Level B). Clinicians should evaluate patients with MCI for modifiable risk factors, assess for functional impairment, and assess for and treat behavioral/neuropsychiatric symptoms (Level B). Clinicians should monitor cognitive status of patients with MCI over time (Level B). Cognitively impairing medications should be discontinued where possible and behavioral symptoms treated (Level B). Clinicians may choose not to offer cholinesterase inhibitors (Level B); if offering, they must first discuss lack of evidence (Level A). Clinicians should recommend regular exercise (Level B). Clinicians may recommend cognitive training (Level C). Clinicians should discuss diagnosis, prognosis, long-term planning, and the lack of effective medicine options (Level B), and may discuss biomarker research with patients with MCI and families (Level C).

Magnetic resonance imaging in multiple sclerosis Analysis of correlations to peripheral blood and spinal fluid abnormalities

MRI of the brain, peripheral blood (PB) T cell subsets and B cells, CSF T cell subsets, CSF IgG concentration and incidence of CSF oligoclonal bands (OB), and plasma cells were studied in 32 clinically suspected MS patients. The CSF in MS patients with MRI lesions showed increased IgG concentration and higher incidence of plasma cells and OB compared with those without MRI lesions. In PB, the percentage of kappa light-chain positive B cells was significantly increased in patients with abnormal MRI as compared with controls. The correlation of MRI of the head and immunologic studies in MS will be helpful in better understanding the pathogenesis and dynamics of the disease.

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.

Reply from the authors [3]

To the Editor: The recently published Practice Advisory was needed, is timely, and is sensible.1 The Therapeutics and Technology Assessment Subcommittee of the AAN found little compelling evidence favoring decompression of leg nerves in diabetic symmetric distal sensorimotor polyneuropathy (DSPN). It should be emphasized that it is decompression of leg nerves at anatomic sites not known to be entrapped that is being discussed (which may not have been sufficiently emphasized in the Advisory) and corrected prevalence figures for DSPN should be provided—the figures provided in the Advisory were for all types of neuropathy (i.e., 66% for type 1 and 59% for type 2 diabetics).1 For DSPN, the estimated prevalence is 54% for type 1 and 45% for type 2 diabetes. The minimal criteria used for the diagnosis of DSPN were two or more abnormalities from among neuropathy symptoms, signs, attributes of nerve conduction, quantitative sensation tests, or heartbeat decrease with deep breathing or Valsalva maneuver (in all cases using standard tests with values corrected for age, gender, and physical variables). When the minimal criterion for DSPN is a composite score of five attributes of nerve conduction of the leg (with values expressed as normal deviates [from percentiles] and with all abnormalities expressed in the upper tail of the normal distribution [summated normal deviates of five attributes of nerve conduction]), the estimated percentages are 55% and 32%. Providing these corrected prevalence values is not meant to detract from the main conclusion of the Advisory.

Teaching NeuroImages: Osteochondroma arising from the clavicle causing ipsilateral Horner syndrome

A 17-year-old female smoker noticed right eyelid droop for 6 months, with a constant right-sided pressure-like headache with photophobia, phonophobia, and nausea, right-sided lacrimation, and right-sided rhinorrhea. Examination revealed right Horner syndrome. A mass was palpable on the anterior aspect of her neck. Ultrasound of the neck, MRI head, and CT thorax showed a bony mass arising from the right medial clavicular head (figure 1). Histopathology from the excision confirmed an osteochondroma (figure 2). This was removed surgically with partial resolution of symptoms. This case demonstrates a rare cause of Horner syndrome1,2 and the importance of thorough imaging of the sympathetic chain.