Faculty Bibliography

Botulinum toxin (BoNT) is a neurotoxin produced by the bacteria Clostridium botulinum that has become widely used for various neurologic indications. The four toxin formulations currently available for use in the United States (approved by the Food and Drug Administration) are onabotulinumtoxinA (Botox^®), abobotulinumtoxinA (Dysport^®), incobotulinumtoxinA (Xeomin^®), and rimabotulinumtoxinB (Myobloc^®). While the FDA-approved labels indicate that potency conversions should not be done, literature supports relative dose equivalents of approximately 1:1:2-4:50-100, respectively. The aim of this paper is to review the evidence on the use of BoNT formulations available in the United States for specific neurologic disorders, including blepharospasm, cervical dystonia (CD), upper and lower extremity spasticity and chronic migraine. Data from the updated 2016 American Academy of Neurology (AAN) guidelines are presented and the level of evidence for use of the four available preparations of BoNT are discussed (Table 2 in appendix). For the management of blepharospasm, the recommendations are for use of onaBoNT-A and incoBoNT-A injections with level B evidence. For the management of CD, the recommendations are for use of aboBoNT-A and rimaBoNT-B with level A evidence. For the management of upper extremity spasticity, the recommendations are for use of aboBoNT-A, incoBoNT-A and onaBoNT-A with level A evidence. For the management of lower extremity spasticity, the recommendations are for use of onaBoNT-A and aboBoNT-A with level A evidence. For the management of chronic migraines, the recommendations are for use of onaBoNT-A to help improve headache-free days, with level A evidence. It is important for the clinician to understand that BoNT is for use in symptomatic control for the underlying neurologic disorder and, at present, has not shown a role in disease modification.

Essential tremor is characterized by persistent, usually bilateral and symmetric, postural or kinetic activation of agonist and antagonist muscles involving either the distal or proximal upper extremity. Quality of life is often affected and one's ability to perform daily tasks becomes impaired. Oral therapies, including propranolol and primidone, can be effective in the management of essential tremor, although adverse effects can limit their use and about 50% of individuals lack response to oral pharmacotherapy. Locally administered botulinum toxin injection has become increasingly useful in the management of essential tremor. Targeting of select muscles with botulinum toxin is an area of active research, and muscle selection has important implications for toxin dosing and functional outcomes. The use of anatomical landmarks with palpation, EMG guidance, electrical stimulation, and ultrasound has been studied as a technique for muscle localization in toxin injection. Earlier studies implemented a standard protocol for the injection of (predominantly) wrist flexors and extensors using palpation and EMG guidance. Targeting of muscles by selection of specific activators of tremor (tailored to each patient) using kinematic analysis might allow for improvement in efficacy, including functional outcomes. It is this individualized muscle selection and toxin dosing (requiring injection within various sites of a single muscle) that has allowed for success in the management of tremors.

BACKGROUND:Neuromyelitis optica spectrum disorder (NMOSD) patients may be at increased risk of venous thromboembolism (VTE) not only due to ambulatory disability but also due to systemic autoimmune and inflammatory mechanisms altering the hemostatic balance. OBJECTIVE:To compare the risk of VTE in NMOSD versus multiple sclerosis (MS) patients hospitalized for acute relapses. METHODS:Hospital admissions for MS or NMOSD exacerbations were retrospectively identified. Demographics and medical history were recorded. The relationship between visit diagnosis and presence of VTE within 6 weeks of relapse onset was assessed by univariate logistic regression. A multivariate model evaluated the relationship between diagnosis, age, race, gender, body mass index (BMI), disease modifying therapy use, oral corticosteroid use, oral contraceptive use, smoking, length of stay (LOS), and ambulatory status on VTE risk. RESULTS:A total of 30 NMOSD patients had 55 hospitalizations; 179 MS patients had 264 hospitalizations. Six NMOSD patients and one MS patient had VTE. NMOSD visits compared to MS visits had an odds ratio (OR) of VTE of 32.2 ( p = 0.002). NMOSD was more likely to be associated with VTE (OR = 17.4; p = 0.01) controlling for age, LOS, and ambulatory disability. CONCLUSION/CONCLUSIONS:NMOSD may be a risk factor for VTE. Larger prospective studies are required to confirm this risk and determine implications for prophylaxis.

Atherosclerosis is a chronic, progressive, multifocal arterial wall disease caused by local and systemic inflammation responsible for major cardiovascular complications such as myocardial infarction and stroke. With the recent understanding that vulnerable plaque erosion and rupture, with subsequent thrombosis, rather than luminal stenosis, is the underlying cause of acute ischemic events, there has been a shift of focus to understand the mechanisms that make an atherosclerotic plaque unstable or vulnerable to rupture. The presence of inflammation in the atherosclerotic plaque has been considered as one of the initial events which convert a stable plaque into an unstable and vulnerable plaque. This paper systemically reviews the noninvasive and invasive imaging modalities that are currently available to detect this inflammatory process, at least in the intermediate stages, and discusses the ongoing studies that will help us to better understand and identify it at the molecular level.