Innovations In Clinical Neuroscience

JAN-FEB 2018

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

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O R I G I N A L R E S E A R C H 31 ICNS Innovations in Clinical Neuroscience • January–February 2018 • Volume 15 • Number 1–2 visits. Participants were predominantly male (82%) with a mean age of 48 years. Most had longstanding HIV with a mean duration of known infection (by self-report) of 15.5 years (SD=9.4). HIVM had been present for 4.2 (SD=5.4) years on average. HIV was well controlled and undetectable in all patients except for one (in the IVIG group) with a viral load of 896 copies/mL. CD4+ counts ranged from 218 to 850 cells/mm 3 with a mean of 592 (SD=212). Muscle dynamometry . Muscle dynamometry was generally well tolerated by participants, and they were all able to complete all the dynamometry procedures, with the exception of two participants who experienced discomfort with the ankle dorsiflexion related to co-existing peripheral neuropathy. Due to this discomfort, it was necessary to modify the dynamometry procedure for one of these participants, using two attempts to generate maximal force instead of the usual four trials. Overall, the dynamometry showed good test-retest reliability as demonstrated by significant correlation between the CDS obtained at the screening and baseline visits for hip flexion (r=0.86, p=0.001), knee flexion (r=0.85, p=0.001), and ankle dorsiflexion (r=0.71, p=0.015). In addition, the CDSs for each anatomic location were highly correlated with one another (hip flexion and knee flexion: r=0.80, p=0.002; hip flexion and ankle dorsiflexion: r=0.81, p=0.001; knee flexion and ankle dorsiflexion r=0.76, p=0.005). The hip flexion and knee flexion CDS were also associated with the HDMS in the expected direction (r= -0.69, p=0.013 and r= -0.634, p=0.027 respectively) although the ankle dorsiflexion score was not. The hip flexion CDS was also correlated with the two-minute timed walk (r=0.78, p=0.004), and there was a trend for correlation between the two-minute timed walk and knee flexion (r=0.60, p=0.051) and ankle dorsiflexion (r=0.56, p=0.71) CDSs. Examination of the dynamometry results over the course of the study revealed that, in general, proximal lower limb (hip flexion and knee flexion) force increased over time, whereas dorsiflexion force declined slightly. When these data were examined according to group assignment (Table 1), the IVIG group had larger increases in force generated on dynamometry. For example, the IVIG group experienced a 22-percent increase in the HFCDS, whereas the placebo group increase was only three percent. As shown in Figure 1, this effect appeared at Week 2 and was maintained until the end-of- study visit. However, we reiterate that these analyses are merely descriptive, given the small sample size, so we cannot exclude the possibility that any perceived between-group differences occurred purely by chance alone. Adverse events and safety . In terms of safety, the infusions were well tolerated. One participant in the IVIG group developed a mild headache toward the end of the second infusion, which resolved spontaneously without specific treatment. There were no significant changes in the monitoring laboratory parameters. DISCUSSION HIVM is a disabling neurological disorder associated with HIV infection for which there is no known effective treatment. There are open-label data to suggest that IVIG might be effective in improving lower-extremity strength in HIVM, and data from other disorders, such as HTLV-1-associated myelopathy, and pathologic data implicating immune mechanisms in the pathogenesis of HIVM, support IVIG as a rational choice. 9–11 However given the expense and inconvenience of IVIG, it is desirable to have more definitive evidence as to its efficacy in HIVM. Thus, we designed the randomized, placebo-controlled feasibility trial described herein. The main conclusion of our study, which sought to enroll 30 participants but succeeded in enrolling only 12 over the course of four years, is that unfortunately a randomized, placebo-controlled trial of IVIG for HIVM that is large enough to provide data adequate to confidently guide clinical decision making is not feasible, at least not as a single-center study. We were unable to do so from within a large healthcare system in New York City, which services approximately 10,000 HIV-infected adults, and so a costly multicenter approach would likely be necessary for successful recruitment large enough to adequately power an IVIG myelopathy study. We believe that the main causes of this recruitment difficulty TABLE 1. Changes in dynamometry from baseline to end-of-study 1 MUSCLE GROUP TOTAL SAMPLE N=11 IVIG GROUP N=5 PLACEBO GROUP N=6 Hip flexion 8.4 (25.4) 14.0 (32.7) 1.9 (13.4) Knee flexion 11.5 (13.8) 12.4 (14.4) 10.3 (14.5) Ankle dorsiflexion -1.8 (7.81) 1.7 (8.2) -6.0 (5.2) Sum of all three 18.2 (40.9) 28.2 (49.2) 6.2 (28.9) 1 All dynamometry measures are an average of right and left, are in units of pound-force (lbf ), and are expressed as mean (standard deviation). FIGURE 1. Percentage change in hip flexion dynamometry composite score following intravenous immunoglobulin treatment

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