Immunogenicity induced by botulinum toxin injections for limb spasticity: A systematic review.

BACKGROUND: The imputability of neutralizing antibodies (NABs) in secondary non-response (SnR) to botulinum toxin (BoNT) injections for limb spasticity is still debated. OBJECTIVE: This systematic literature review aimed to determine the prevalence of NABs after BoNT injections for limb spasticity and analyze their determinants and their causal role in SnR. METHODS: We searched MEDLINE via PubMed, Cochrane and Embase databases for articles published during 1990-2018. Two independent reviewers extracted the data and assessed the quality of studies with a specific scale (according to PRISMA and STROBE guidelines). Because the techniques used to detect NABs did not influence the results, we calculated the global (all studies) sensitivity and specificity of NAB positivity to reveal SnR. RESULTS: We included 14 articles published from 2002 to 2018 (including an epublication) describing 5 randomized controlled trials and 5 interventional and 4 observational studies. The quality was satisfactory (mean score 18/28 arbitrary units). NAB detection was the primary criterion in 5 studies and a secondary criterion in 9. In total, 1234 serum samples for 1234 participants (91% with stroke) were tested after injection. NAB prevalence was about 1%, with no significant difference among formulations. NAB positivity seemed favoured by long-duration therapy with high doses and a short interval between injections. The identification of non-response by NAB positivity had poor global sensitivity (56%) but very high specificity (99.6%). No consensual criteria were used to diagnose non-response to BoNT injection. CONCLUSIONS: NAB prevalence is much lower after BoNT treatment for limb spasticity than cervical dystonia. Consensual criteria must be defined to diagnose non-response to BoNT injection. Because immunogenicity is not the most common cause of non-response to BoNT injection, NABs should be sought in individuals with SnR with no other cause explaining the treatment inefficacy. A test with 100% specificity is recommended. In cases for which immunogenicity is the most likely cause of non-response to BoNT injections, some biological arguments suggest trying another BoNT, but no clinical evidence supports this strategy.

Specificity of Lower Urinary Tract Symptoms in Neuromyelitis Optica in Comparison With Multiple Sclerosis Patients.

PURPOSE: The aim of this study was to describe lower urinary tract symptoms in neuromyelitis optica (NMO), and to compare these data with urinary disorders observed in multiple sclerosis (MS) patients. METHODS: Retrospective study of data collected from January 1997 to July 2017 using the database from a Neuro-Urology Department of a university hospital. NMO and MS patients were matched for sex, age, and Expanded Disability Status Scale (EDSS). RESULTS: Twenty-six patients with NMO were included and compared with 33 MS patients. Mean age was 41.6 years (standard deviation [SD], 14,8), mostly female patients (24 vs. 2 males). Mean EDSS was 4.6 (SD, 1.8) in the 2 groups. In NMO group, 57% of the patients (n=15) had overactive bladder with urgency and urge incontinence and 38.5% (n=10) of them had nocturia. Voiding symptoms was observed in 69.2% of the patients (n=18); 42.3% of NMO patients performed self-intermittent catheterization versus 12.1% in MS patients (P=0.012). Low bladder compliance and severe urinary tract infections (pyelonephritis) were more frequent in NMO than in MS patients (respectively 15% vs. 0%, P=0.016 and 42% vs. 12%, P=0.024). CONCLUSION: Lower urinary tract symptoms, especially overactive bladder and urinary retention, are frequent in NMO. Low bladder compliance, serious urinary infections, and high prevalence of urinary retention requiring self-intermittent catheterization are the main symptoms significantly more frequent than in MS.