Publications by Author: Andrea M Sartori

OBJECTIVES: To summarize the current literature on lower urinary tract electrical sensory assessment (LUTESA), with regard to current perception thresholds (CPTs) and sensory evoked potentials (SEPs), and to discuss the applied methods in terms of technical aspects, confounding factors, and potential for lower urinary tract (LUT) diagnostics.

METHODS: The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Medline (PubMed), Embase and Scopus were searched on 13 October 2020. Meta-analyses were performed and methodological qualities of the included studies were defined by assessing risk of bias (RoB) as well as confounding.

RESULTS: After screening 9925 articles, 80 studies (five randomized controlled trials [RCTs] and 75 non-RCTs) were included, comprising a total of 3732 patients and 692 healthy subjects (HS). Of these studies, 61 investigated CPTs exclusively and 19 reported on SEPs, with or without corresponding CPTs. The recording of LUTCPTs and SEPs was shown to represent a safe and reliable assessment of LUT afferent nerve function in HS and patients. LUTESA demonstrated significant differences in LUT sensitivity between HS and neurological patients, as well as after interventions such as pelvic surgery or drug treatments. Pooled analyses showed that several stimulation variables (e.g. stimulation frequency, location) as well as patient characteristics might affect the main outcome measures of LUTESA (CPTs, SEP latencies, peak-to-peak amplitudes, responder rate). RoB and confounding was high in most studies.

CONCLUSIONS: Preliminary data show that CPT and SEP recordings are valuable tools to more objectively assess LUT afferent nerve function. LUTESA complements already established diagnostics such as urodynamics, allowing a more comprehensive patient evaluation. The high RoB and confounding rate was related to inconsistency and inaccuracy in reporting rather than the technique itself. LUTESA standardization and well-designed RCTs are crucial to implement LUTESA as a clinical assessment tool.

BACKGROUND AND OBJECTIVE: Most patients with neurourological disorders require lifelong medical care. The European Association of Urology (EAU) regularly updates guidelines for diagnosis and treatment of these patients. The objective of this review is to provide a summary of the 2024 updated EAU guidelines on neurourology.

METHODS: A structured literature review covering the timeframe 2021-2023 was conducted for the guideline update. A level of evidence and a strength rating were assigned for each recommendation on the basis of the literature data.

KEY FINDINGS AND LIMITATIONS: Neurological conditions significantly affect urinary, sexual, and bowel function, and lifelong management is required for neurourological patients to maintain their quality of life and prevent urinary tract deterioration. Early diagnosis and effective treatment are key, and comprehensive clinical assessments, including urodynamics, are crucial. Management should be customised to individual needs and should involve a multidisciplinary approach and address sexuality and fertility. Lifelong monitoring and follow-up highlight the importance of continuous care for neurourological patients.

CONCLUSIONS AND CLINICAL IMPLICATIONS: The 2024 EAU guidelines on neurourology provide an up-to-date overview of available evidence on diagnosis, treatment, and follow-up for neurourological patients.

PATIENT SUMMARY: Neurological disorders very frequently affect the lower urinary tract and sexual and bowel function and patients need lifelong management. We summarise the updated European Association of Urology guidelines on neurourology to provide patients and caregivers with the latest insights for optimal health care support.

Most human spinal cord injuries are anatomically incomplete, leaving some fibers still connecting the brain with the sublesional spinal cord. Spared descending fibers of the brainstem motor control system can be activated by deep brain stimulation (DBS) of the cuneiform nucleus (CnF), a subnucleus of the mesencephalic locomotor region (MLR). The MLR is an evolutionarily highly conserved structure which initiates and controls locomotion in all vertebrates. Acute electrical stimulation experiments in female adult rats with incomplete spinal cord injury conducted in our lab showed that CnF-DBS was able to re-establish a high degree of locomotion five weeks after injury, even in animals with initially very severe functional deficits and white matter lesions up to 80-95%. Here, we analyzed whether CnF-DBS can be used to support medium-intensity locomotor training and long-term recovery in rats with large but incomplete spinal cord injuries. Rats underwent rehabilitative training sessions three times per week in an enriched environment, either with or without CnF-DBS supported hindlimb stepping. After 4 weeks, animals that trained under CnF-DBS showed a higher level of locomotor performance than rats that trained comparable distances under non-stimulated conditions. The MLR does not project to the spinal cord directly; one of its main output targets is the gigantocellular reticular nucleus in the medulla oblongata. Long-term electrical stimulation of spared reticulospinal fibers after incomplete spinal cord injury via the CnF could enhance reticulospinal anatomical rearrangement and in this way lead to persistent improvement of motor function. By analyzing the spared, BDA-labeled giganto-spinal fibers we found that their gray matter arborization density after discontinuation of CnF-DBS enhanced training was lower in the lumbar L2 and L5 spinal cord in stimulated as compared to unstimulated animals, suggesting improved pruning with stimulation-enhanced training. An on-going clinical study in chronic paraplegic patients investigates the effects of CnF-DBS on locomotor capacity.

Neurogenic lower urinary tract dysfunction typically develops after spinal cord injury. We investigated the time course and the anatomical changes in the spinal cord that may be causing lower urinary tract symptoms following injury. Rats were implanted with a bladder catheter and external urethral sphincter electromyography electrodes. Animals underwent a large, incomplete spinal transection at the T8/9 spinal level. At 1, 2-3, and 4 weeks after injury, the animals underwent urodynamic investigations. Urodynamic investigations showed detrusor overactivity and detrusor-sphincter-dyssynergia appearing over time at 3-4 weeks after injury. Lower urinary tract dysfunction was accompanied by an increase in density of C-fiber afferents in the lumbosacral dorsal horn. CRF-positive Barrington's and 5-HT-positive bulbospinal projections drastically decreased after injury, with partial compensation for the CRF fibers at 3-4 weeks. Interestingly, a decrease over time was observed in the number of GABAergic neurons in the lumbosacral dorsal horn and lamina X, and a decrease of glutamatergic cells in the dorsal horn. Detrusor overactivity and detrusor-sphincter-dyssynergia might therefore arise from a discrepancy in inhibitory/excitatory interneuron activity in the lumbosacral cord as well as input changes which develop over time after injury. The processes point to spinal plastic changes leading to malfunction of the important physiological pathway of lower urinary tract control.

BACKGROUND: Deep brain stimulation (DBS) has clear beneficial effects on motor signs in movement disorders, but much less is known about its impact on lower urinary tract (LUT) function.

OBJECTIVE: To evaluate the effects of DBS on LUT function in patients affected by movement disorders.

DESIGN, SETTING, AND PARTICIPANTS: We prospectively enrolled 58 neurological patients affected by movement disorders, who were planned to receive DBS.

INTERVENTION: DBS in the globus pallidus internus, ventral intermediate nucleus of the thalamus, or subthalamic nucleus.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Subjective symptom questionnaires (International Prostate Symptom Score) and objective urodynamic studies were carried out before implantation of the DBS leads and several months after surgery. After DBS surgery, urodynamic investigations were performed with DBS ON as well as DBS OFF.

RESULTS AND LIMITATIONS: We enrolled patients suffering from Parkinson's disease (n = 39), dystonia (n = 11), essential tremor (n = 5), Holmes tremor (n = 2), and multiple sclerosis with tremor (n = 1). DBS of the globus pallidus internus resulted in worsening of LUT symptoms in 25% (four of 16) of the cases. DBS of the subthalamic nucleus in patients with Parkinson's disease led to normalization of LUT function in almost 20% (six of 31 patients), while a deterioration was seen in only one (3%) patient. DBS of the ventral intermediate nucleus of the thalamus improved LUT function in two (18%) and deteriorated it in one (9%) patient with tremor.

CONCLUSIONS: DBS effects on LUT varied with stimulation location, highly warranting patient counseling prior to DBS surgery. However, more well-designed, large-volume studies are needed to confirm our findings.

PATIENT SUMMARY: In this report, we looked at outcomes of deep brain stimulation on lower urinary tract function. We found that outcomes varied with stimulation location, concluding that counseling of patients about the effects on lower urinary tract function is highly recommended prior to surgery.

Despite the fact that a majority of patients with an injury to the spinal cord develop lower urinary tract dysfunction, only few treatment options are available currently once the dysfunction arises. Tibial nerve stimulation has been used in pilot clinical trials, with some promising results. Hence, we investigated whether the early application of transcutaneous tibial nerve stimulation in the animal model of spinal cord injured rats can prevent the development of detrusor overactivity and/or detrusor-sphincter-dyssynergia. Rats were implanted with a bladder catheter and external urethral sphincter electromyography electrodes. A dorsal over-hemisection, resulting in an incomplete spinal cord injury at the T8/9 spinal level, induced immediate bladder paralysis. One week later, the animals received daily tibial nerve or sham stimulation for 15 days. Effects of stimulation on the lower urinary tract function were assessed by urodynamic investigation. Measurements showed improvements of several key parameters of lower urinary tract function-in particular, non-voiding bladder contractions and intravesical pressure-immediately after the completion of the stimulation period in the stimulated animals. These differences extinguished one week later, however. In the dorsal horn of the lumbosacral spinal cord, a small significant increase of the density of C-fiber afferents layers I-II was found in the stimulated animals at four weeks after spinal cord injury. Tibial nerve stimulation applied acutely after spinal cord injury in rats had an immediate beneficial effect on lower urinary tract dysfunction; however, the effect was transitory and did not last over time. To achieve more sustainable, longer lasting effects, further studies are needed looking into different stimulation protocols using optimized stimulation parameters, timing, and treatment schedules.

CONTEXT: Neurourological patients often encounter bacteriuria without any symptoms or may experience symptoms suspicious of urinary tract infections (UTIs). However, there is a lack of guidelines that unequivocally state the definition of UTIs in this specific patient group.

OBJECTIVE: To present all used definitions of UTIs in neurourological patients.

EVIDENCE ACQUISITION: This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Studies were identified by electronic search of Medline, Embase, Cochrane controlled trials databases, and clinicaltrial.gov without a time limitation (last search September 2020) and by screening of reference lists and reviews. The occurrences of the various UTI definitions were counted and the frequencies calculated.

EVIDENCE SYNTHESIS: After screening 7164 abstracts, we included 32 studies enrolling a total of 8488 patients with a neurourological disorder who took part in an interventional clinical study. UTI definitions were heterogeneous. The concordance to predefined definitions was low.

CONCLUSIONS: Interventional clinical studies rarely report specific definitions for UTIs, and both clinical and laboratory criteria used are heterogeneous. A generally accepted UTI definition for neurourological patients is urgently needed.

PATIENT SUMMARY: Patients suffering from neurological disorders often experience symptoms in their lower urinary tract that resemble urinary tract infections. Furthermore, they can have positive urine cultures without symptoms (the so-called asymptomatic bacteriuria). However, clinical studies rarely report specific definitions for urinary tract infections, and when it is done, they are heterogeneous. A generally accepted urinary tract infection definition for neurourological patients is urgently needed. TAKE  HOME MESSAGE: Interventional clinical studies on neurourological patients rarely report specific definitions for urinary tract infections (UTIs), and both clinical and laboratory criteria used are heterogeneous. A generally accepted UTI definition for neurourological patients is urgently needed.

Lower urinary tract dysfunction affects a multitude of patients. Current therapeutic approaches are limited and very little is known about the mechanisms in failure of bladder control. Thus, more basic research is clearly needed to elucidate the underlying pathological mechanisms and to develop novel treatment strategies in urology. Noninvasive tests such as the void-spot assay and the metabolic cage and more invasive urodynamics investigations are currently used to assess lower urinary tract function in animals, in particular rodents. The noninvasive tests give some insights into the functionality of the system, whereas urodynamics testing yields an objective evaluation that allows distinction of different pathologies and investigations of the underlying neuronal malfunctions. PATIENT SUMMARY: We briefly summarize methods currently used to assess impairments of bladder function in animal models. Both noninvasive and invasive methods are available and can be used to understand and improve human health. An accurate and detailed diagnosis is, however, possible only with urodynamics assessments.

BACKGROUND: Ultrasound is generally used to measure postvoid residual (PVR) in daily clinical practice for a basic assessment of voiding dysfunction. In animal research, however, PVR is measured mostly by expelling the urine with gentle squeezing of the bladder.

OBJECTIVE: To assess the translational value of measuring PVR by ultrasound in awake rats with the aim of obtaining directly comparable data sets in patients and rodent models.

DESIGN, SETTING, AND PARTICIPANTS: A prospective animal study was conducted in 10 rats with large, incomplete thoracic spinal cord injury resulting in severe bladder impairment. Lower urinary tract function was assessed by urodynamics with implanted bladder catheter and external urethral sphincter electrodes, allowing for repeated measurements over time. Immediately after the last micturition cycle in the urodynamic investigation, PVR was first assessed by ultrasound using a 7.5 MHz linear probe and then by manually expelling the urine via gentle pressure on the abdomen.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PVR was measured by ultrasound and by manually expelling the urine. Paired t test was used to analyze the difference between the two measurements 1 and 2 wk after spinal cord injury.

RESULTS AND LIMITATIONS: PVR assessed by ultrasound was equal to and not statistically different from the volumes obtained by manual expulsion in intact rats, both before injury and during the first 2 wk after spinal cord injury (intact: 0.16 ± 0.07 vs 0.14 ± 0.09 ml, p =  0.08; week 1: 1.67 ± 0.53 vs 1.71 ± 0.55 ml, p =  0.67; week 2: 1.16 ± 0.35 vs 0.98 ± 0.43 ml, p =  0.11). The main limitation of ultrasound for measuring PVR is the restricted availability of ultrasound machines in animal research laboratories.

CONCLUSIONS: Ultrasound is a valuable translational tool to measure PVR in awake rats reflecting the situation in humans.

PATIENT SUMMARY: We measured postvoid residual by ultrasound in awake rats, analogous to clinical examination in humans. Ultrasonography provided similar values to the generally used manual bladder expulsion.

CONTEXT: Controversy still exists regarding the balance of benefits and harms for the different surgical options for neurogenic stress urinary incontinence (N-SUI).

OBJECTIVE: To identify which surgical option for N-SUI offers the highest cure rate and best safety without compromising urinary tract function and bladder management.

EVIDENCE ACQUISITION: A systematic review was performed under the auspices of the European Association of Urology Guidelines Office and the European Association of Urology Neuro-Urology Guidelines Panel according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement.

EVIDENCE SYNTHESIS: A total of 32 studies were included. Overall, 852 neurourological patients were surgically treated for N-SUI. The treatment offered most often (13/32 studies) was an artificial urinary sphincter (AUS; 49%, 416/852) and was associated with a need for reintervention in one-third of patients. More than 200 surgical revisions were described. Overall, 146/852 patients (17%) received concomitant bladder augmentation, mainly during placement of an AUS (42%, 62/146) or autologous sling (34% of women and 14% of men). Following pubovaginal sling placement, dryness was achieved in 83% of cases. A significant improvement in N-SUI was observed in 87% (82/94) of women following placement of a synthetic midurethral sling. Efficacy after insertion of an adjustable continence therapy device (ACT 40%, proACT 60%) was reported for 38/128 cases (30%). The cure rate for bulking agents was 35% (9/25) according to 2/32 studies, mainly among men (90%). The risk of bias was highly relevant. Baseline and postoperative cystometry were missing in 13 and 28 studies, respectively.

CONCLUSIONS: The evidence is mainly reported in retrospective studies. More than one intervention is often required to achieve continence because of coexisting neurogenic detrusor overactivity, low compliance, or the onset of complications in the medium and long term. Urodynamic data are needed to better clarify the success of N-SUI treatment with the different techniques.

PATIENT SUMMARY: Our review shows that insertion of an artificial urinary sphincter for urinary incontinence is effective but is highly associated with a need for repeat surgery. Other surgical options may have lower continence rates or a risk of requiring intermittent catheterization, which patients should be informed about before deciding on surgery for their incontinence.