Ice Water Test (IWT) was first described in 1957 by Bors and Blinn as a pertinent test to discriminate an upper motorneuron lesion from a lower motorneuron lesion, using human cooling bladder reflex, mediated by C-fibers cold receptors (1). Several studies suggested that IWT could unmask Detrusor Activity (DO) in patients complaining about overactive bladder (OAB) or determine the neurological status of patients with DO or OAB (1), with encouraging results but not sufficient enough to install IWT in common practice. 
The aim of this study was to determine psychometric properties of IWT to predict the appearance of a detrusor activity in patients with neurogenic acontractile detrusor

We retrospectively reviewed medical files of patients followed in the neuro-urology unit of our department of Physical and Rehabilitation Medicine (PRM) between January 2008 and May 2018. 

Patients

Patients older than 18 presenting a neurogenic acontractile detrusor as defined by the ICS following spinal injury and cauda equina were eligible (3). We included all patients presenting no bladder contraction at first cystometry, performed in accordance with the International Continence Society standards immediately followed by an IWT. Bladder was filled with cold water (4°C) at a 100ml/min (1). Test was considered positive if it induced a non-inhibited detrusor contraction ≥ 15cmH2O, with or without leakage. Moreover, patients treated by antimuscarinics or any drugs with anticholinergic effect were excluded. Medical files were reviewed for the following data: age, date of lesion, urodynamic data (bladder sensation, compliance, detrusor activity), voiding mode and treatments. Voluntary or uninhibited contraction during yearly urodynamic follow-up was considered for the analysis. We thus considered the time elapsed between the lesion and the first appearance of detrusor activity observed in cystometry and the delay between the lesion and the last cystometry in patients without any detrusor activity.  
Primary outcome was the calculation of IWT predictive values to determine appearance of a detrusor activity in patients with neurogenic acontractile detrusor. 

Ethics
Our database was approved by the French Data Protection Authority (Commission Natoinale Informatique et Libertés – CNIL) under the agreement number 2209010 V0, in accordance with the French Legislation for retrospective studies.

Statistics
Contingency tables were drawn to determine sensitivity (Se), specificity (Sp) predictive values (positive or negative, respectively PPV or NPV), and accuracy of IWT as a predictor of the recovery of a detrusor activity. Continuous variables were expressed as means with standard deviations, and time elapsed data were presented with median [first-third quartile]. T-test assessed the statistical association between 2 qualitative variables. Statistical analysis was performed using Prism V5 (GraphPad software – La Jolla, CA, USA).

Forty-eight patients were included in final analysis. Twenty-four patients presented a clinically Suprasacral spinal cord/pontine lesion (SSL) (NLI assessed with the ASIA scale) either cervical (n=3), thoracic (n=10), lumbar (n=8), conus (n=2) or undefined (n=1). Twenty-four patients presented clinical Sacral Spinal Cord Lesion (SSCL). Their baseline characteristics are presented in Table 1. 

IWT had a Sp of 0.91 IC95%[0.76-0.98], Se of 0.93 IC95%[0.66-1], PPV of 0.81 IC95%[0.59-0.93] and NPV of 0.97 IC95%[0.82-1], with a 0.92 IC95%[0.80-0.98] accuracy (table 2). 

Fourteen patients regained a detrusor activity, among whom 13 had a positive IWT at first cystometry. Three  had spontaneous micturition without significant post voiding residue, 3 had spontaneous micturition associated with ISC and 2 had reflex micturition and surgical sphincterotomy. 

Among the 32 patients with negative IWT, only one recovered a spontaneous detrusor activity 5,2 years after the lesion and 3,7 years after the initial IWT with an annual cystometry follow-up and was treated with antimuscarinics. All these patients used intermittent catheterization.

This study is the first to demonstrate the relevance of IWT to predict the detrusor activity in patients with initial neurogenic acontractile detrusor with relevant clinical outcome and good psychometric properties. 
Indeed, time elapsed between the lesion and detrusor activity appearance was 2,03 [1,4-4,5] years post lesion, underlining the need of an intensive follow-up in patients with positive IWT at least the 2 first years following the lesion. Remarkably, NPV of IWT was very high, allowing clinician to decrease the follow-up of these patients. 
These results suggest that a positive IWT could indicate a change in the threshold of provoking afferent fibers in patients with emerging C-fiber function following SCI, still unsensitive to conventional cystometry. 

Limitations 
IWT has been demonstrated to be positive in other conditions such as Bladder Outlet Obstruction (BOO) (2). We did not record BOO, in this population. However, no statistical differences between male and female (data not shown) was found in our study suggesting that positivity of IWT was solely related to the neurogenic condition.  This was a retrospective study with a small number of patients. However, in order to increase strength of this study, we only included patients with isolated and non-evolutive lesion who were naïve of any antimuscarinic treatment at first urodynamics. Finally, we have to consider an inclusion bias, resulting of our strict inclusion criteria to avoid confounding factors, thus generalization of our results in other population of patients could be limited.

IWT could be a suitable test with robust psychometric properties to predict emergence of detrusor activity in patients after SCI or Cauda equina with neurogenic acontractile detrusor. Although further studies are needed, these results could lead us to an open-field of improvement of management of patients suffering with neurogenic bladder, with a proportional follow-up depending on detrusor activity emergence.

Al-Hayek S, Abrams P. The 50-Year History of the Ice Water Test in Urology. Journal of Urology. mai 2010;183(5):1686-92.
Hellström PA, Tammela TL, Kontturi MJ, Lukkarinen OA : The bladder cooling test for urodynamic assessment: analysis of 400 examinations. Br J Urol. 1991 Mar;67(3):275-9.
Gajewski JB, Schurch B, Hamid R et al. An International Continence Society (ICS) report on the terminology for adult neurogenic lower urinary tract dysfunction (ANLUTD). Neurourol Urodyn. 2018;37:1152-1161.