Prognostic impact of epileptic seizures in multiple sclerosis varies according to time of occurrence and etiology.

BACKGROUND AND PURPOSE: Epileptic seizures occur more often in patients with multiple sclerosis (MS) than in the general population. Their association with the prognosis of MS remains unclear. This study was undertaken to evaluate whether epileptic seizures may be a prognostic marker of MS disability, according to when the seizure occurs and its cause. METHODS: Data were extracted from a population-based registry of MS in Lorraine, France. Kaplan-Meier curves and log-rank tests were used to compare the probability of different levels of irreversible handicap during the course of MS in patients who experience epileptic seizures or do not, according to the chronology and the cause of the first epileptic seizure. RESULTS: Among 6238 patients, 134 had experienced at least one epileptic seizure (2.1%), and 82 (1.2%) had seizures secondary to MS. Patients with epileptic seizure as a first symptom of MS (14 patients) had the same disease progression as other relapsing-remitting MS patients. Patients who developed epileptic seizures during the course of MS (68 patients) had a higher probability of reaching Expanded Disability Status Scale = 3.0 (p = 0.006), 6.0 (p = 0.003), and 7.0 (p = 0.004) than patients without an epileptic background. Patients with a history of epileptic seizures unrelated to MS also had a worse prognosis than patients without an epileptic background. CONCLUSIONS: Epileptic seizures might be viewed as a "classic MS relapse" in terms of prognosis if occurring early in MS, or as a marker of MS severity if developing during the disease. Epileptic diseases other than MS may worsen the course of MS.

Neurological consequences of recreational nitrous oxide abuse during SARS-CoV-2 pandemic.

INTRODUCTION: Recreational use of nitrous oxide (N2O) is a growing practice in France and all around the world and is often associated with neurological complications. We report detailed clinical and paraclinical presentations of 12 patients with combined degeneration of the spinal cord and peripheral neuropathies in relation to N2O consumption, possibly favored by lockdowns due to SARS-CoV-2 pandemic. RESULTS: With variable levels of consumption, the 12 patients presented spinal cord and/or peripheral nerve damage, with mostly motor and ataxic symptoms, motor axonal nerve damage, and medullary T2-weighted hyperintensities on MRI. There was a clear improvement in symptoms after vitamin B12 substitution, although some sequelae remained, particularly sensory. DISCUSSION: We report detailed clinical, electrophysiological, radiological, and biological consequences of N2O abuse in 12 patients. Our data support the clinical and paraclinical observations reported in the literature. The mechanisms of neurological N2O toxicity are still debated. There is currently no precise recommendation on the therapeutic management. The clinical evolution after vitamin B12 substitution seems sufficient but could depend on early management. Effective messages targeting at risk population, but also the health professionals involved, seem crucial as does a better legal framework for this growing practice.

Effect of radical prostatectomy on involuntary pelvic floor muscle contraction.

AIMS: Radical prostatectomy may cause stress urinary incontinence (SUI). We compared continent and incontinent men after radical prostatectomy, in regard to the change of the temporal pattern of pelvic floor activation during cough. METHODS: Twenty-two patients were included in this prospective, multicentric study. All patients gave their informed consent. Simultaneous recordings of electromyographic activity of external anal sphincter (EAS EMG) and external intercostal muscle (EIC EMG) during cough were performed with a pair of pregelled surface electrodes. Cough effort caused an involuntary pelvic contraction. Intercostal muscles recording was chosen because they are one of the muscular components of cough initiation with diaphragm muscle. Twenty-four-hour pad-weighing test was used to quantify urinary incontinence. The primary endpoint was the latency between the onset of EIC EMG and EAS EMG (RT3), during a cough effort. We also measured the contraction time, the maximum EAS EMG activity, and the area under the curve. RESULTS: All the patients were analyzed: 12 continent and 10 with SUI. The median age was 66 years old. Both groups were similar except in term of follow-up. Median latency was increased by -1.7 ms (-47.9; +34.2) to 55.8 ms (+47.5; +80) in patients with SUI (P = 0.0033; Table 2). The duration of the contraction, the maximum EAS EMG activity and the area under the curve were not different. CONCLUSIONS: The latency between the onset of EIC EMG and EAS EMG is increased in patients with SUI after radical prostatectomy. It may be one of the reasons for SUI in these patients.

Predictive factors of adherence to urinary self-catheterization in older adults.

AIMS: The primary aim is to explore the adherence predicting factors in clean intermittent self-catheterization (CISC) in patients aged over 65 years. The secondary aim is to assess whether in this population, the non-adherence risk is greater, compared with patients under 65. METHODS: All patients older than 65 that successfully learned CISC between January 2011 and January 2016 were included. A control population younger than 65 matched with sex, body mass index, and pathology was selected. RESULTS: One hundered and thirteen (66.9%) out of the 169 patients older than 65 included were adherent at 1 month, and 80 (47.3%) at 6-12 months. Obesity (P = 0.027), a low PP test (Pencil and Paper test) score (P = 0.037), significant urinary stress incontinence (SUI) (P = 0.048), and prescription of CISC less than three per day (P = 0.03) were the risk factors predicting stopping CISC at 1 month, but none was associated with non-adherence at 6-12 months. Compared with the younger group, age was a risk factor for poor adherence at 1 month. CONCLUSION: Obesity, low PP test score, and important SUI are factors of poor adherence to CISC at 1 month in older adults. Necessity of more than three CISC per day is in favor of treatment continuation, possibly due to absence of spontaneous voiding in these patients. Long-term adherence to CISC in older adults in this study remains close to adherence to other treatments prescribed in urinary disorders, and thus shows that CISC could be an easily purposed therapeutic option in this population, either on a long-term or transitory basis.

Diffusion-Weighted Magnetic Resonance Imaging: A New Tool for the Diagnosis of Bladder Pain Syndrome/Interstitial Cystitis.

OBJECTIVES: To determine whether diffusion-weighted magnetic resonance imaging (DWMRI), a noninvasive procedure, can contribute to the diagnosis of bladder pain syndrome/interstitial cystitis (BPS/IC). METHODS: The pelvic DWMRI of patients with chronic pelvic pain syndrome was selected between January 2012 and June 2017. A radiologist analyzed the bladder wall signal; he was blinded to the patients' clinical data. According to the 2008 European Society for the Study of Bladder Pain Syndrome/Interstitial Cystitis criteria, 2 groups of patients were determined: BPS/IC and no BPS/IC. The association between BPS/IC and the wall signal intensity was compared. RESULTS: In the 106 patients included, 82 had criteria for BPS/IC and 24 did not. A significant difference in the distribution of the signal was found between the 2 groups (p = 0.01). High signal intensity of the bladder wall was related to the presence of a BPS/IC with a sensitivity of 28% and a specificity of 88%. No signal intensity of the bladder wall was related to the absence of a BPS/IC with a sensitivity of 96% and a specificity of 29%. CONCLUSIONS: In -DWMRI, high bladder wall signal intensity helps to affirm a BPS/IC, whereas the absence of signal helps to exclude the diagnosis. Further studies are needed to confirm these preliminary results.

Lower urinary tract symptoms treatment constraints assessment (LUTS-TCA): a new tool for a global evaluation of neurogenic bladder treatments.

OBJECTIVES: To develop a new tool to assess constraints due to urinary treatments in neurological patients. MATERIALS AND METHODS: A prospective, monocentric study has been conducted from January to May 2017. Out-patients (multiple sclerosis, spinal cord injury, Parkinson disease) were included in a referral center if they had LUTS treatment for at least 3 months. To validate psychometric properties, we conducted a literature review, qualitative interviews, and discussion with a panel of six experts. Comprehension, acceptation, and pertinence were tested by a pilot study. A validation study, designed to calculate content validity, internal consistency reliability, and test-retest reliability [intraclass correlation coefficient (ICC)] has been conducted. The primary outcome was good psychometric properties defined with Cronbach's α > 0.7 and ICC > 0.7. RESULTS: Comprehension, acceptation, and pertinence were excellent. Validation study showed a perfect content validity (r2 = 1) and excellent internal consistency reliability (Cronbach' α = 0.90). Total score was between 0 (best score) to 66 (maximal constraints). Test-retest reliability calculated using ICC was 0.81. Time to fill questionnaire was 4 min 20 s. The final version was composed by 22 items. CONCLUSION: LUTS TCA is the first validated tool to assess constraints of urinary treatment and has excellent psychometric properties.

Nocturnal Urinary Disorders and Multiple Sclerosis: Clinical and Urodynamic Study of 309 Patients.

PURPOSE: The aim of this study was to describe nocturia with or without leakage in a population of patients with multiple sclerosis. MATERIALS AND METHODS: This is a retrospective, single center study of 309 patients with multiple sclerosis who were followed at an experienced neurourology center between 2011 and 2013. All patients had daytime urinary symptoms associated with this disorder. Among the patients with nocturia 2 groups were defined, including those with isolated nocturia but without nocturnal urinary incontinence and patients with nocturia associated with nocturnal urinary incontinence. The control group comprised patients without nocturia. The clinical variables and urodynamic data studied were gender, age, EDSS (Expanded Disability Status Scale), the USP (Urinary Symptoms Profile) questionnaire overactive bladder score, bladder capacity, detrusor activity and volume at the first detrusor contraction. RESULTS: Of our patients 53.3% had nocturia, including 35.7% with nocturnal urinary incontinence. The average ± SD USP overactive bladder score was statistically greater in patients with nocturia than in controls (9.14 ± 4.3 vs 5.1 ± 3.5, p = 8.21E-17). Mean maximum cystometric capacity was statistically higher in the control group than in patients with nocturia (380.17 ± 113.79 vs 313 ± 128.4 ml, p = 5.60E-6). A similar outcome was found for the first contraction (mean 232.58 ± 146.05 vs 181.14 ± 100.11 ml, p = 0.041). CONCLUSION: Isolated nocturia or nocturnal urinary incontinence is a frequent problem encountered with multiple sclerosis. Our results suggest that an overactive detrusor is the main mechanism. Further studies are needed to verify the complications arising from nocturia.

Neutralizing antibodies and fatigue as predictors of low response to interferon-beta treatment in patients with multiple sclerosis.

BACKGROUND: The clinical impact of neutralizing antibodies against interferon-beta (NAb) is controversial. Their presence can lead to a decrease in interferon-beta (IFNß) efficacy. Fatigue reported in patients with multiple sclerosis (MS) may be associated with an unfavorable clinical course. We conducted a prospective multicentre study to assess the association between response to IFNß, NAb and fatigue. METHODS: Patients with relapsing-remitting MS on IFNß treatment were included. During the second year of treatment, the patients were analyzed for NAb status and non-response criteria to IFNß (number of relapses ≥1 during the follow-up period, increase in the Expanded Disability Status Scale ≥0.5). The score on the Modified Fatigue Impact Scale (MFIS pathological if score ≥35) was noted for each patient. RESULTS: Of the 176 patients included: 22.3% were NAb positive, 54.5% presented non-response criteria to IFNß, and 57.4% had a pathological MFIS score. Fatigue was increased in NAb + patients (p = 0.0014) and they were more likely to present non-response criteria to IFNß (p = 0.041) than NAb- patients. Multivariate logistic regression analysis showed that the presence of NAb was related to fatigue (p = 0.0032) and denoted disease activity in these patients (p = 0.026). CONCLUSIONS: This study demonstrates the impact of NAb on the non-clinical response to IFNß. Fatigue assessment is an indicator of IFNß responsiveness and a predictive biomarker of deterioration on patient's neurological status.

Unaltered regulatory B-cell frequency and function in patients with multiple sclerosis.

Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) typically characterized by the recruitment of T cells into the CNS. However, certain subsets of B cells have been shown to negatively regulate autoimmune diseases and some data support a prominent role for B cells in MS physiopathology. For B cells in MS patients we analyzed subset frequency, cytokine secretion ability and suppressive properties. No differences in the frequencies of the B-cell subsets or in their ability to secrete cytokines were observed between MS and healthy volunteers (HV). Prestimulated B cells from MS patients also inhibited CD4(+)CD25(-) T cell proliferation with a similar efficiency as B cells from HV. Altogether, our data show that, in our MS patient cohort, regulatory B cells have conserved frequency and function.