A retrospective study was conducted: all patients with NMOSD referred for urinary disorders in a Neuro-Urology Department of a University Hospital between January 1997 and July 2017 were included. Inclusion criteria were patients with an established diagnosis of NMOSD (clinical, and magnetic resonance imaging [MRI] criteria before 2005 and clinical, biological and MRI criteria after 2005). Patients with MS diagnosed according to the revised criteria of Mc Donald’s were identified [18]. Each patient with NMOSD was matched with at least 1 or 2 MS patients for sex, age, and according to the Expanded Disability Status Scale (EDSS) [19].

For each patient, clinical and urodynamic data were collected: age, sex, severity of neurological disability measured by the EDSS, and duration of follow-up. Patients were classified into 3 categories according to the EDSS: from 1 to 4, 4.5 to 6.5, and more than 7. The first group was patients with EDSS from 1 to 4, the second class with EDSS from 4.5 to 6.5, the third with 7 and more.

The symptoms existing during the first clinical evaluation were noted and divided between the storage symptoms such as urgency, nocturia, stress urinary incontinence (SUI), and urgency urinary incontinence; and the voiding symptoms (slow stream, intermittent stream, hesitancy, straining to void), the urinary treatments during the first clinical evaluation were also noted, as well as the use of intermittent catheter as voiding mode. The existence of urinary infection during the last year were searched with difference between urinary infection without fever and pyelonephritis

The urodynamic parameters from the first urodynamic evaluation were documented with: the existence of detrusor overactivity (phasic or terminal), the volume of the first involuntary detrusor contraction, the maximum intravesical pressure during the evaluation, the presence of a low bladder compliance (the compliance is calculated by dividing the volume change by the change in detrusor pressure during that change in bladder volume, a compliance=20 or less is considered as low), the cystometric capacity, the presence of a detrusor sphincter dyssynergia (DSD). During the evaluation if the patient presented a post void residual of 100 mL or more, it was considered as urinary retention.

Using an echography, the presence of vesicoureteral reflux or lithiasis, as well as a renal failure on biology, was resumed in “morphological complications.”

The urodynamic studies were performed according to “the Good Urodynamic Practice” recommended by the International Continence Society [20]. All definitions used were in accordance with the International Continence Society Report [21].

Descriptive statistics were expressed as the mean±standard deviation (SD). Differences between groups were assessed with the Student t-test for quantitative variables and chi-square or Fischer tests for categorical variables. Statistical analyses were carried out using R software ver. 3.3 (R Foundation for Statistical Computing, Vienna, Austria) with a P<0.05 considered significant.

This study was approved by the local ethics committee (Comité de Protection des Personnes Ile de France II: 00001072). Since it was a retrospective study, no formalized informed consent was necessary according to the ethics committee, and a letter was sent to the patients informing them that their data would be used, unless they contacted the investigators to express their disapproval.

Twenty-six patients with NMOSD were included with a mean age of 41.6 years (SD, 14.8). Most of the patients were women (93.9%, n=24 patients). Only 2 patients had an EDSS higher than seven. 57.7% (n=15) of the patients had urgency, 57.7% (n=15) urge incontinence, 26.9% (n=7) SUI, and 38.5% (n=10) had nocturia. Voiding symptoms was observed in 69.2% of the patients (n=18), and 42.3% used self-intermittent catheterization as voiding mode. The duration of follow-up in NMOSD population was 8.2 years (SD, 7.8).

Nine NMOSD patients were treated by means of anticholinergic drugs (34.6%), 6 received alpha-adrenergic blocking drug (23.1%), and 2 used botulinum toxin A injections in detrusor (7.7%) in association with self-intermittent catheterization (Table 1).

Concerning urodynamic data, 12 patients had detrusor overactivity (46.1%) and the mean cystometry capacity was 356.3 mL (SD, 140.4). Ten patients had DSD (38.4%) and 4 patients (15.4%) had a low bladder compliance (Table 2).

Mean EDSS was 4.6 (SD, 1.8) in the 2 groups. Febrile urinary tract infection (pyelonephritis and prostatitis) were significantly higher in the NMOSD population than in MS patients (30.4% vs. 6.1%; P=0.024). Low bladder compliance was more frequent in NMOSD patients than in MS (15.4% vs. 0% P=0.016). Voiding symptoms with significant postvoid residual volume requiring self-intermittent catheterization was more frequent in NMOSD patients than in MS (42.3% vs. 12.1%; P=0.012).

A comparison between the patients with a low bladder compliance and the others, showed a significative increase of the pyelonephritis incidence in the group “low bladder compliance” (50.0% vs. 12.5%, P=0.038).

The existence of a DSD was significantly associated with the presence of voiding symptoms (87.5%, n=28, P=0.033) and urgency urinary incontinence (59.4%, n=19, P=0.743). There was not any strong association between DSD and low bladder compliance (3.4%, n=1, P=0.475) or pyelonephritis incidence (6.2%, n=2, P=0.052)

There was no other significant difference concerning clinical or urodynamic characteristics between NMOSD and MS populations.

The NMOSD is a chronic inflammatory disease that affects the central nervous system and which seems to be very close of MS. But in fact, there are several characteristics that differentiate MS and NMOSD:

· The evolution of NMOSD is more pejorative than MS [15].

· Some treatments used in MS, did not work on NMOSD patient [22].

· NMOSD has a lower incidence than MS [23].

As there were differences between NMOSD and MS, we supposed that urinary disorders were different in both diseases. The initial speculation was that NMOSD had more urologic complications (pyelonephritis, vesicoureteral reflux, or renal failure, …).

This supposition was based on several arguments:

· Myelitis is common in NMOSD, and it’s well known that urinary complications are more serious in spinal cord injury [9].

· NMOSD is an active disease with pejorative evolution leading to a degradation of the voiding control (on the contrary of spinal cord injury).

· NMOSD is often confused with MS, leading to lack of data on urinary disorders in this specific disease.

Our results confirm that there was more pyelonephritis and low compliance bladder in NMOSD group. These results seem to confirm that the urinary disorders are more severe in NMOSD patients than MS patients.

As we already say NMO is an active disease like MS, but with spinal injury (myelitis). In other terms, NMO combine the more serious urinary complication (because of myelitis), and the progressive degradation of neural voiding control (like MS). With this observation, we understand that we cannot applied a similar medical reasoning than MS or spinal cord injury.

We propose that every patient with NMOSD diagnosis is referred to Neuro-Urology Department event no specific urinary symptom is observed. The follow-up for these patients should be the same than spinal cord injury patients: over a 2 years period, at 6-month intervals at the beginning and then every year in order to monitor the neurological degradation. As a same way the treatment proposed needs to be more aggressive early. The treatment must be re-evaluated for each step of functional loss.

Characteristics of our population in term of urinary disorders are similar to 2 previous studies concerning urinary function in NMOSD. The first one reported the prevalence of LUTS in a population of NMOSD followed prospectively and showed that most of these patients had significant LUTS including urgency, nocturia, and voiding symptoms. The most frequent urodynamics findings were DSD (present in over half of the patients) and overactive bladder [7]. The authors suggested that DSD was the most common urodynamic abnormality in NMOSD, in contrast with MS. On the contrary, in our study, there is no significant difference between MS and NMOSD patients concerning prevalence of overactive bladder and/or DSD. The second study was a cross-sectional study, investigating the bowel and bladder dysfunction and their impact on quality of life in 60 NMOSD patients. In this article, 78% patients reported bladder symptoms, 60% had urgency, 47% had incontinence, and 39% had nocturia. Moreover, 45% of the patients had a moderate or severe bowel problem, 79% were constipated and 23% had fecal incontinence [8]. In our study, we observed the same prevalence of overactive bladder symptoms (urgency [57.7%], urge incontinence [57.7%], nocturia [38.5%]) but voiding symptoms was more frequently observed (69.2%) than in the previous studies. Similarly, we found a high prevalence of constipation (64%).

Nevertheless, there are some limitations in this work, the most important is the retrospective nature of this study. This retrospective nature leads to several biases, such as memory or selection biases, inducing a lack of power. Moreover because of the specialization of our department, we create a selection bias; because our patients are consulting for LUTS. However, this expertise allowed us to find a cohort of 26 patients with NMOSD, which is a consequent population because of the illness rarity, comparing to MS [24].

In conclusion, to our best knowledge, we report here the first clinical and urodynamic comparison between NMOSD and MS patients. We found a significant difference between the 2 populations, concerning the prevalence of febrile urinary infections, the importance of voiding dysfunction and urinary retention requiring the use of self-intermittent catheterization, and presence of low bladder compliance in NMO. Despite the limitations of our study due to retrospective analysis, we can suggest that the LUTS observed in NMOSD are more important than in MS and can lead to more severe complications. A further and prospective study could demonstrate a possible difference in term of efficacy concerning the specific urinary treatment.