Marks, Lisa

Background: Functional movement disorders (FMD, aka psychogenic movement disorders) are very common and frequently chronic and disabling. Despite this, there is a paucity of evidence-based treatment to manage and alleviate these conditions. Specialized physical therapy (PT), involving sequential motor relearning and redirecting attention, has shown promise as a therapeutic intervention for motor symptoms. Methods: The objective of this study was to critically assess current evidence regarding specialized PT compared with usual care in improving motor symptoms among patients with FMD. This was addressed through the development of a structured critically appraised topic. This included a clinical scenario with a clinical question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, and content experts in the fields of physical medicine and rehabilitation, physical and occupational therapy, psychiatry, and psychology. Results: A randomized controlled feasibility trial was identified and selected for critical appraisal. This study randomized 60 patients with FMD to a 5-day specialized outpatient PT program or to general outpatient PT referral, and measured patient-reported and clinician-measured outcomes. At 6 months, 72% of patients in the intervention group had a good outcome compared with 18% of control group patients. Patients in the specialized outpatient PT program had significantly better outcomes in 3 Short-Form 36 (SF36) domains (d=0.46 to 0.79) and multiple other scales of physical and social function as well as clinician-measured outcomes. The intervention resulted in 0.08 additional quality-adjusted life years in a cost-effective manner. Conclusions: Current evidence suggests that in patients with FMD, specialized PT improves motor symptoms in a clinically significant, sustained, and cost-effective manner. This promising intervention warrants further investigation and replication.

Background: High-dose chemotherapy followed by autologous stem cell transplantation (HD-ASCT) is a promising alternative to whole brain radiation therapy (WBRT) in the treatment of primary central nervous system lymphoma (PCNSL). The objective of this study was to critically assess current evidence supporting the use of HD-ASCT as first-line consolidative therapy in PCNSL. Methods: The objective was addressed through the development of a critically appraised topic that included a clinical scenario, structured question, literature search strategy, critical appraisal, assessment of results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and a content expert in the field of neuro-oncology. Results: A recent, open-label, noncomparative randomized phase II trial was selected for critical appraisal. This trial evaluated the efficacy and toxicity of consolidative therapy with HD-ASCT and WBRT in PCNSL in 2 separate treatment arms. A total of 140 patients with newly diagnosed PCNSL between the ages of 18 and 60 years were included. The primary endpoint of 2-year progression-free survival was met in 63% of patients in the WBRT arm and 87% in the HD-ASCT arm. Notably, an overall improvement in neurocognitive scores was observed following HD-ASCT, while WBRT was associated with worsened cognitive outcomes. Conclusions: In young patients with newly diagnosed PCNSL, consolidative therapy with HD-ASCT appears to be associated with less neurocognitive toxicity and may be more effective than WBRT at preventing relapses, however, at the cost of a higher treatment-related mortality.

Background: Stroke is a leading cause of disability worldwide. Selective serotonin reuptake inhibitors are often prescribed following stroke due to high rates of depression. Interest in selective serotonin reuptake inhibitor use for poststroke motor and functional recovery was generated after the publication of the Fluoxetine for motor recovery after acute ischemic stroke (FLAME) trial in 2011, which showed improved motor recovery in ischemic stroke patients with moderate to severe motor deficits. The objective of this study was to critically assess current evidence regarding the use of fluoxetine compared with placebo for poststroke functional recovery. Methods: The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario and question, literature search, critical appraisal, results, evidence summary, commentary, and clinical bottom line conclusions. Participants included consultant and resident neurologists, medical librarian, clinical epidemiologists, and content experts in the field of cerebrovascular neurology and physical medicine and rehabilitation. Results: A randomized, placebo-controlled clinical trial was selected for critical appraisal. This trial compared the functional outcomes of subjects poststroke receiving fluoxetine versus placebo. There was no significant difference in functional outcome measured by the Modified Rankin Scale between the 2 groups. Prespecified secondary analysis showed significantly decreased rates of depression in the fluoxetine group, but significantly increased rates of bone fracture. Conclusion: Among patients with stroke, early initiation of fluoxetine did not result in improved functional recovery. Lower rates of depression were observed in the fluoxetine-treated group; however these patients experienced higher rates of bone fracture.

Background:Concussion affects almost 4 million individuals annually. There are many sideline screening tools available to assist in the detection of sports-related concussion. The King-Devick (K-D) test in association with Mayo Clinic utilizes rapid number naming to test saccadic eye movements in order to screen for concussion. An ideal screening tool for concussion would correctly identify all athletes with active concussion. The accuracy of K-D testing compared with other sideline screening tools is undetermined.Objective:To critically assess current evidence regarding the utility of K-D testing as a sideline screening tool for acute concussion and compare K-D testing to other sideline concussion assessments.Methods:The objective was addressed through the development of a critically appraised topic that included a clinical scenario, structured question, literature search strategy, critical appraisal, assessment of results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of concussion neurology and neuro-ophthalmology.Results:A recent meta-analysis was selected for critical appraisal. Cohorts analyzing athletes with sports-related concussion were selected, and utilized K-D testing as the main baseline and sideline assessment of concussion. K-D testing was found to have a high sensitivity and specificity for detecting concussion when there was worsening from baseline.Conclusion:K-D testing has high sensitivity and specificity for detecting sideline concussion. Compared with other sideline screening tools that do not include vision testing, it has greater accuracy. Screening for concussion is optimized when multiple testing modalities are used in conjunction.

AbstractAimTo identify the appropriate methods of synovial fluid (SF) specimen storage, manipulation and handling for crystal associated arthritides (CAA) diagnosis.MethodA systematic literature review was conducted using 5 medical databases to identify diagnostic studies assessing SF specimen handling for calcium pyrophosphate (CPP) and monosodium urate (MSU) crystals identification. All included studies were rated for quality using the Quality Assessment of Diagnostic Accuracy Studies 2.ResultsFifteen studies, including 2 non‐English language manuscripts, were included. Eight studies examined both types of crystals, while 3 studies examined CPP and 4 studies examined MSU crystals only. Overall, MSU crystals were more stable over time compared to CPP crystals. MSU stability was generally independent of time, preservative and temperature. CPP crystals deteriorated with time and were more stable if refrigerated. Ethylenediaminetetraacetic acid (EDTA) was a suitable preservative. Re‐examining an initially negative SF sample at 24 hours facilitated detection of additional cases. Very few studies had an overall low risk of bias and applicability.ConclusionMonosodium urate crystals remain stable over time independent of storage time, temperature and preservative. CPP crystals are mostly stable for 24‐48 hours but can deteriorate with time. Overall, SF crystal examination should ideally be done within 24‐48 hours. They may be stored at room temperature without any preservative. Otherwise, refrigeration (4°C/39°F) and EDTA preservation is reasonable. Stored SF re‐examination, at 24 hours, helps identify a small number of additional MSU and CPP cases. Centrifugation techniques allow better and easier crystal identification, particularly CPP. Most studies were of unclear or low quality.

Objectives To address concerns related to the safety profile of both Food and Drug Administration (FDA)–approved and non‐FDA‐approved intranasal corticosteroid (INCS) use in the pediatric population. Data Source Systematic review of MEDLINE, PubMed, and EMBASE databases using comprehensive search strategy, including all INCS formulations and adverse events. The study design was developed using Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Additional sources were identified from study references of relevant articles. Review Methods A structured literature search was conducted. Extracted data included age, population size, study design, drug (dosage, route, and frequency), presence of hypothalamic‐pituitary‐adrenal (HPA) axis suppression, ocular symptoms, and growth velocity adverse events. Results A total of 33 studies met inclusion criteria. The studies included use of INCS as nasal sprays and drops. There were no persistent abnormalities noted in cortisol level or intraocular pressure change. Growth velocity reduction was reported in 3 of 10 randomized trials. Meta‐analysis of epistaxis and headache showed no significant difference in the incidence of headache or epistaxis when FDA‐approved INCSs were compared to placebo, with a relative risk of 1.12 (95% CI, 0.77‐1.63; P =. 56) and 0.84 (95% CI, 0.60‐1.18; P =. 32), respectively. Meta‐analysis was not performed for growth velocity, HPA axis suppression, and ocular change. Conclusions INCSs in FDA‐approved routes of administration are generally safe to use in the pediatric population. Use of non‐FDA‐approved INCS drops may increase risk of iatrogenic Cushing’s syndrome. Growth velocity reduction, HPA axis suppression, and visual changes due to INCS are uncommon.

Background: Noninvasive neuromodulation devices have been used for a variety of headache disorders, including cluster and migraine, since recently being cleared by the Federal Drug Administration. Although these devices have been touted as low-risk options for improved headache control, the data behind actual efficacy endpoints remain unclear. Objective: To critically assess current evidence regarding the efficacy of the noninvasive vagus nerve stimulator (nVNS) device for acute migraine management. Methods: The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario with a clinical question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and a content expert in the field of headache. Results: A randomized, double-blind, sham-controlled clinical trial was selected for critical appraisal. In this trial, the primary endpoint (pain freedom at 120 min after use of nVNS for first acute migraine attack) was not met when compared with sham device (30.4% for nVNS vs. 19.7% for sham; P=0.067). However, there were statistically significant differences found for various secondary endpoints favoring nVNS, such as pain freedom rates at 30 and 60 minutes, pain relief at 120 minutes, and mean percentage pain score reduction rates at 60 and 120 minutes. Conclusions: When comparing nVNS with sham, no statistically significant differences were found with regards to the primary endpoint of pain freedom at 120 minutes, although differences were found with various secondary endpoints and post hoc analysis. nVNS is likely a safe alternative to medications.

ObjectivesTo address concerns related to the safety profile of both Food and Drug Administration (FDA)–approved and non–FDA‐approved intranasal corticosteroid (INCS) use in the adult population.Data SourceSystematic review of MEDLINE, PubMed, and EMBASE databases using a comprehensive search strategy including all INCS formulations and adverse events. The study design was developed using Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Additional sources were identified from study references of relevant articles.Review MethodsA structured literature search was conducted. Each study was graded for level of evidence using the Oxford Centre for Evidence‐Based Medicine. Extracted data included population size, study design, drug (dosage, route, and frequency), presence of hypothalamus pituitary axis suppression, ocular symptoms, and treatment‐related adverse events.ResultsA total of 60 studies met inclusion criteria. The studies included use of INCS as metered nasal sprays, drops, injections, aerosols, and irrigations. There were no persistent abnormalities in cortisol level or intraocular pressure change. Meta‐analysis of epistaxis showed a significantly increased risk in the FDA‐approved treatment group in comparison with control (risk ratio 1.56; 95% confidence interval, 1.13‐2.14; P =. 007).ConclusionsOverall, it appears that the use of both FDA and published non‐FDA application of INCS are safe in the adult population. Meta‐analysis demonstrated an increased risk of epistaxis in patients using INCS compared with placebo. Otherwise, there was no significant difference between in adults in the treatment group and placebo group. As an important caveat, the interpretation of safety of nonstandard INCS is restricted to delivery methods and dosages published in the literature.

INTRODUCTION: Acute portal vein thrombosis (PVT) is a rare diagnosis frequently associated with cirrhosis. Clinical presentation is typically nonspecific with potentially catastrophic short-term complications including sepsis, bowel infarction, and death. Management strategies differ for acute and chronic PVT. Guidelines for treating acute PVT recommend immediate initiation of systemic anticoagulation. Direct and indirect thrombolytic therapy (mechanical thrombectomy and fibrinolytic therapy) may be used in combination with systemic anticoagulation in the setting of bowel ischemia or as an adjunct in patients with a contraindication to systemic anticoagulation. We aimed to assess the success of thrombolytic therapy for non-malignant acute PVT and to compare the success of direct versus indirect thrombolytic therapy. METHODS: This was a systematic review and meta-analysis in which two independent librarians searched the following databases from the date of inception to March 2019: Ovid Medline, Ovid Embase, Scopus and Web of Science. All included studies provided technical and clinical success data, as well as adverse events, and technique(s) used for the intervention of non-malignant acute PVT. RESULTS: The two independent database searches yielded 143 citations, of which 79 duplicates were removed leaving a total of 64 references and 11 were included in our analyses. The overall success rate of thrombolytic therapy using the random effects model was 83% (95%CI: 0.67, 0.92; P = <0.01; I 2 = 61%). The overall clinical improvement rate of thrombolytic therapy using the fixed effects model was 95% (95%CI: 0.88, 0.98; P = 0.73; I 2 = 0%). The overall mortality of thrombolytic therapy using the fixed effects model was 5% (95%CI: 0.03, 0.11; P = 0.92; I 2 = 0%). In the direct and indirect thrombolytic groups, the rate of technical success was 84% and 52%, respectively, with an odds ratio of 3.37 (95%CI (0.96, 7.67), P -value = 0.127). CONCLUSION: Our analysis demonstrates that thrombolytic therapy successfully eliminates non-malignant acute PVTs with low rates of mortality. Direct thrombolysis may produce increased efficacy compared to indirect thrombolytic therapy. Larger prospective randomized trials comparing these interventions are warranted.