Innovations In Clinical Neuroscience

JAN-FEB 2018

A peer-reviewed, evidence-based journal for clinicians in the field of neuroscience

Issue link: http://innovationscns.epubxp.com/i/935919

Contents of this Issue

Navigation

Page 27 of 53

28 ICNS Innovations in Clinical Neuroscience • January–February 2018 • Volume 15 • Number 1–2 O R I G I N A L R E S E A R C H H Human immunodeficiency virus (HIV)- associated myelopathy (HIVM) is a rare but well-described neurologic complication of HIV; it was first described early in the acquired immunodeficiency syndrome (AIDS) epidemic, and is still observed today despite the widespread use of combination antiretroviral therapy (CART). 1–3 HIVM manifests clinically at any stage of HIV infection, with slowly progressive weakness in the lower extremities, gait disorder, sensory abnormalities in the legs, sexual dysfunction, and urinary and bowel control abnormalities. 4 There is currently no proven effective treatment for HIVM, and treatment focuses on symptomatic therapies, including antispasticity agents, management of sphincter dysfunction, and physical therapy. The pathogenesis of HIVM is unknown. HIV itself has been detected in the spinal cord only rarely, and there is no correlation between the presence or severity of HIVM and the presence of HIV in the spinal cord, CD4+ lymphocyte cell count, or HIV viral load in plasma or cerebrospinal fluid. 5,6 The histopathology of HIVM bears some resemblance to that of subacute combined degeneration due to vitamin B12 deficiency, where vacuolization is attributed to diminished production of S-adenosyl-methionine. Given these similarities, prior studies have sought to demonstrate whether high doses of oral L-methionine supplementation would be beneficial for the treatment of HIVM. However although a preliminary open-label trial was promising— demonstrating clinical and electrophysiological improvement of HIVM, a larger double-blind, placebo-controlled study showed no effect. 7,8 Since neither treatment of metabolic pathways with L-methionine nor treatment of HIV itself with CART has been effective in ameliorating the symptoms of HIVM, there has been interest in the possibility of secondary immunologically mediated mechanisms. This concept is supported by certain pathological findings in HIVM, which, in addition to vacuolization, include inflammatory infiltrates. 9 Furthermore, immunologic mechanisms appear to be important in another retroviral A B S T R A C T Objective: Open-label data suggest that intravenous immunoglobulin (IVIG) might improve lower- extremity strength in human immunodeficiency virus (HIV)-associated myelopathy (HIVM), a rare but debilitating neurologic complication of HIV. We sought to determine the feasibility of testing the efficacy of IVIG for HIVM more rigorously. Design: We conducted a randomized, double-blind, placebo- controlled feasibility trial of IVIG for HIVM, using dynamometry as an outcome measure (Clinical Trial No. NCT01561755). Setting: The study took place in an academic medical center in New York, New York Participants: Only 12 participants were enrolled in four years; critical impediments to the study were the rarity of patients with new HIVM diagnoses and prior exposure to IVIG in patients with an established diagnosis. Measurements: Dynamometry of hip flexion, knee flexion, and ankle dorsiflexion were measured; the HIV Dementia Motor Score (HDMS); and the two-minute timed walk test were utilized. Results: Recruitment was the major feasibility issue. Dynamometry was generally well-tolerated, had good test-retest reliability (r=0.71–0.86, p<0.02 for all muscle groups), and good inter-item reliability as judged by the correlations between the muscle groups (r=0.76-0.81, p=0.001–0.005). Dynamometry was valid and clinically meaningful based on its correlations with the HDMS and the two-minute timed walk test. Conclusion: We conclude that an adequately powered clinical trial of IVIG for HIVM would likely require a prolonged recruitment period and multiple participating sites. Lower limb dynamometry is a useful outcome measure for HIVM, which might also be useful in other HIV-related gait disorders. Keywords: Dynamometry, intravenous immunoglobulin (IVIG), human immunodeficiency virus (HIV), myelopathy Lower-extremity Dynamometry as a Novel Outcome Measure in a Double-blind, Placebo-controlled, Feasibility Trial of Intravenous Immunoglobulin (IVIG) for HIV- associated Myelopathy by JESSICA ROBINSON-PAPP, MD, MS; MARY CATHERINE GEORGE, MM, PhD; ALEXANDRA NMASHIE, MD; DONALD WEISZ, PhD; and DAVID M. SIMPSON, MD Drs. Robinson-Papp, George, Nmashie and Simpson are with the Department of Neurology and Dr. Weisz is with the Department of Neurosurgery—all from the Icahn School of Medicine at Mount Sinai in New York, New York. Innov Clin Neurosci. 2017;15(1–2):28–32 FUNDING: This investigator-initiated project was supported by a grant from CSL Behring. The project was also supported by Grant Number #UL1TR000067 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH). The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of NCATS or NIH. DISCLOSURES: The authors report no financial arrangements between any author and any company whose product or competing product plays a role in the manuscript. This manuscript discusses an unlabeled use of a commercial product: IVIG is not labeled for the treatment of HIV-associated myelopathy. CORRESPONDENCE: Jessica Robinson-Papp, MD, MS, FAAN; Email: jessica.robinson-papp@mssm.edu

Articles in this issue

Links on this page

Archives of this issue

view archives of Innovations In Clinical Neuroscience - JAN-FEB 2018