Factors implicated in pathogenesis of urinary tract infections in neurogenic bladders: some revered, few forgotten, others ignored.

AIMS: To comprehensively review factors implicated in the pathogenesis of urinary tract infection in patients with neurogenic bladders, and to stimulate research, especially in the somewhat ignored and forgotten areas of this important clinical subject. METHODS: In addition to reviewing relevant articles on pubmed, some important articles from previous times which were not available online were also procured and reviewed. RESULTS: Intrinsic defence mechanisms including protective flora, anti-adherence mechanisms, urothelial, and immunological responses to bacterial binding and the blood supply to the urinary bladder may be impaired in patients with neurogenic bladders. Further, bacterial washout mechanisms may be compromised as a result of inefficient voiding, reflux, and altered hydrokinetics. Finally, catheterization itself contributes to urinary tract infection in patients with neurogenic bladders. CONCLUSIONS: In order to address the issue of urinary tract infection in patients with neurogenic bladders, multiple factors need to be looked into and corrected. Further research is required, especially in the area of compromised host defence mechanisms. An individualized approach, which attempts to optimize each factor is recommended.

B cell infiltration and lymphonodular hyperplasia in bladder submucosa of patients with persistent bacteriuria and recurrent urinary tract infections.

PURPOSE: We defined chronic inflammatory cell types in bladder submucosa and the presence of umbrella cells on the surface of bladder epithelium in patients 5 to 21 years old with persistent bacteriuria due to neurogenic bladder and recurrent urinary tract infections associated with vesicoureteral reflux. MATERIALS AND METHODS: Bladder mucosa biopsies from 12 patients and 6 controls were fixed in Carnoy's solution and examined for T cells (CD3, CD4, CD8), B cells (CD79) and plasma cells (CD138). The number of cells in a defined area of submucosa was determined by counting all nuclei in the area. A contiguous section was also stained for uroplakin expression with a monoclonal antibody against uroplakin III to ascertain the integrity of bladder umbrella cells. RESULTS: B cells, plasma cells and lymphoid nodules were found only in patient biopsies. T cell expression was evident in patient and control biopsies. Uroplakin staining of surface epithelium was uniform from control biopsies but spotty or entirely absent from patient biopsies. CONCLUSIONS: Patients with persistent bacteriuria or recurrent urinary tract infections had significant B cell infiltration in the submucosa, including lymphoid nodules. These inflammatory changes are likely due to antigenic stimulation from repeated exposure to bacteria. These changes are associated with frequent absence of uroplakin on surface epithelium.

Neurogenic bladder in an adolescent woman with an ovarian tumour: an unusual presentation of anti-NMDA-receptor encephalitis.

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is rarely seen in women with ovarian teratoma. It is characterised by neuropsychiatric symptoms and may also cause autonomic imbalance. We present the case of a 16-year-old nulliparous woman who presented with an acute history of seizures and neurogenic bladder. Antiviral and antiepileptic therapy conferred no therapeutic benefit. A cystic pelvic mass measuring 185×140×92 mm was identified separate from the bladder. Serum titres of NMDA receptor antibodies were significantly elevated. The mass was surgically removed and histology revealed benign ovarian teratoma with NMDA receptors. The patient made a rapid improvement and had full resolution of urinary and neuropsychiatric symptoms within 1 year. This case demonstrates that increased awareness in adolescents is crucial for avoiding symptom dismissal, misdiagnosis and inappropriate treatment of this condition. Surgical removal of the teratoma should be the first line therapy of anti-NMDA-receptor encephalitis as this often leads to symptom resolution soon after.

Bladder dysfunction in mice with experimental autoimmune encephalomyelitis.

The vast majority of patients with multiple sclerosis (MS) develop bladder control problems including urgency to urinate, urinary incontinence, frequency of urination, and retention of urine. Over 60% of MS patients show detrusor-sphincter dyssynergia, an abnormality characterized by obstruction of urinary outflow as a result of discoordinated contraction of the urethral sphincter muscle and the bladder detrusor muscle. In the current study we examined bladder function in female SWXJ mice with different defined levels of neurological impairment following induction of experimental autoimmune encephalomyelitis (EAE), an animal model of central nervous system inflammation widely used in MS research. We found that EAE mice develop profound bladder dysfunction characterized by significantly increased micturition frequencies and significantly decreased urine output per micturition. Moreover, we found that the severity of bladder abnormalities in EAE mice was directly related to the severity of clinical EAE and neurologic disability. Our study is the first to show and characterize micturition abnormalities in EAE mice thereby providing a most useful model system for understanding and treating neurogenic bladder.

Case of primary Sjogren's syndrome preceded by dystonia.

There are only six cases in literature that describe development of dystonia with Sjogren's syndrome (SS). We describe a case of a 43-year-old woman who presented with symptoms including movement disorder, sensory neurogenic bladder, sensory loss and neuropathic pain, migraine like headaches, musculoskeletal pain, Raynaud's phenomenon and dysautonomia. Symptoms started in 2000, with weakness that progressed to dystonia in 2003. Diagnostic work-up was inconclusive with negative inflammatory serologies, cerebrospinal fluid and MRI for many years. After patient developed sicca syndrome with dry eyes and mouth in 2009, her rheumatoid factor titre was elevated (550 IU/mL), erythrocyte sedimentation rate, anti-Sjogrens syndrome-related antigen A (anti-Ro/SSA) and anti-SSB/La: anti-Sjogrens syndrome-related antigen B (anti-La/SSB) became positive. Lip biopsy confirmed diagnosis of SS. She was diagnosed with primary SS with neurological involvement. Her symptoms responded well to intravenous methylprednisolone. Symptoms stabilised with trials of immune-suppressive therapy. This is a case that demonstrates the delay of diagnosing SS with preceding unique neurological association.

[Urinary concentration of proinflammatory cytokines with regard to infected urinary tract region]. / Stezenie cytokin prozapalnych w moczu w zaleznosci od umiejscowienia zakazenia w drogach moczowych.

UNLABELLED: Uropathogenic bacteria stimulate epithelial cells of interstitial tissue and macrophages to secrete proinflammatory cytokines: interleukin I (IL-1beta), interleukin 6 (IL-6) and interleukin 8 (IL-8). The aim of the study was to check: 1) if the concentration of proinflammatory cytokines (IL-1beta, IL-6, IL-8) differs in dependence on region and clinical picture of urinary tract infection, 2) what is the influence of antibacterial treatment on their concentration. MATERIAL: We examined 67 children, aged 1-15 years, who were divided into 3 groups: 27 children with acute pyelonephritis (AP), caused by E. coli (group I), in whom the examination was carried out twice: A - before treatment, B - after 14 days of antibacterial treatment, 10 children with chronic urinary tract infection (UTI) associated with neurogenic bladder (group II) and 30 healthy children (group K). METHOD: Urinary concentration of examined cytokines was assessed using ELISA immunoenzymatic method and was expressed in pg/mg creatinine. Results showed that in group I before treatment the urinary concentration of examined cytokines was increased (p<0.05). After antibacterial treatment concentration of IL-1beta was normal and concentration of IL-6 and IL-8 decreased but was still higher than in control group (p<0.05). In group II before treatment the increase in concentration of IL-1beta and IL-8 was not so high (p<0.05) and the urinary concentration of IL-6 was normal (p>0.05). In examination A in children from group I and II a positive correlation between examined cytokines and C reactive protein was shown. We have also found a positive correlation between urinary concentration of IL-1beta a IL-8. CONCLUSIONS: 1. Urinary concentration of examined proinflammatory cytokines is different in children with AP and UTI associated with neurogenic bladder and correlates with concentration of C-reactive protein. 2. In most of children with AP after 14-days of antibacterial treatment the urinary concentration of proinflammatory cytokines has been increased.

Appraisal of the stability of leukocytes in refrigerated urine.

There is limited evidence that urinary leukocytes are rapidly destroyed in alkaline hypotonic urine. We assessed the stability of leukocytes in urine specimens provided by 90 children with neurogenic bladder who attended a meningomyelocele clinic. No significant correlation was found between urine specific gravity and leukocyte survival after an interval of 4 h in a sample of 30 specimens from these patients. The survival of leukocytes was determined at 2 h and at 4 h in aliquots of these 30 specimens directly, and after adjustment to pH values of 5.0, 7.0, 8.0, 8.5, and 9.0. Statistically significant leukocyte destruction only occurred at pH 9.0 at 2 h (16%), at pH 8.5 at 4 h (19%), and at pH 9.0 at 4 h (57%). Only one of a further sample of 180 routine specimens had both a pH of > or = 8.5 and an interval to laboratory examination of > 2 h. No specimen had a specific gravity of < 1.002, and 93.9% had values of > or = 1.005. Urine pH and tonicity were not therefore important determinants of leukocyte stability in refrigerated samples examined within 4 h from this clinic population.

The prevalence of antibody-coated bacteria in urine.

The prevalence of urinary antibody-coated bacteria (ACB), suggesting renal bacteriuria, was studied in three groups of patients: inpatients whose physicians suspected urinary tract infections, asymptomatic outpatients with neurogenic bladders but without urethral catheters, and asymptomatic inpatients with indwelling urethral catheters. The prevalence of ACB was 67% of inpatients with positive cultures without catheters, 94% of patients with neurogenic bladders, and 36% of patients with urethral catheters. These results suggest a high prevalence of upper urinary tract involvement in patients with positive urine cultures, even if asymptomatic.

Antibody formation following botulinum toxin type A (Dysport) injection in children with intractable bladder hyper-reflexia.

OBJECTIVES: To investigate the pattern of anti-Dysport antibody (ADA) formation after Dysport injection in patients with neuropathic bladder. Antibody formation may lead to failure or allergic reactions in patients undergoing Dysport injection. METHODS: Forty-four children with neuropathic bladder were enrolled and classified into 3 groups: group I, without history of previous injection (n = 8); group II, with history of one or more injections (n = 7); and group III, who had been injected 3-36 months before this study (n = 29). Groups I and II were subjected to Dysport injection. Fifty-five age-matched healthy children were selected as controls. Urinary incontinence score was assessed before and 6 months after injection. Under cystoscopic guidance, Dysport (10 IU/kg) was injected into the detrusor muscle, sparing the trigone and ureteral orifices. ADA level was measured by enzyme-linked immunosorbent assay technique before injection and then monthly for at least 4 months in groups I and II, and for just once in group III and control subjects. RESULTS: ADA level was increased 1-2 months after the last injection in 3 (38%) of group I and 5 (71%) of group II. However, ADA level in group III was not higher than controls. All patients had complete or partial improvement in urinary incontinence score except for 1 patient in group I. No resistance to treatment was detected. CONCLUSIONS: Increment of ADA titer in patients is not permanent. Repeated injections will not boost the immune system to produce higher levels of antibody. Increased levels of ADA may not be associated with treatment failure at follow-up visit.

FTY720 reduces inflammation and promotes functional recovery after spinal cord injury.

A robust and complex inflammatory cascade is known to be a prominent component of secondary injury following spinal cord injury (SCI). Specifically, the concept of trauma-induced autoimmunity has linked the lymphocyte population with neural tissue injury and neurologic deficit. FTY720, a sphingosine receptor modulator that sequesters lymphocytes in secondary lymphoid organs, has been shown to be effective in the treatment of a variety of experimental autoimmune disorders. Accordingly, by reducing lymphocyte infiltration into the spinal cord following SCI, this novel immunomodulator may enhance tissue preservation and functional recovery. In the present study, a moderate to severe contusion SCI was simulated in adult Long-Evans hooded rats. Using flow cytometry we showed that daily FTY720 treatment dramatically reduced T-cell infiltration into the SCI lesion site at 4 and 7 days post-injury, while other inflammatory cell populations were relatively unaltered. To assess functional recovery, three groups of injured animals (treated, vehicle, and injury only) were evaluated weekly for hindlimb recovery. Animals in the treated group consistently exhibited higher functional scores than animals in the control groups after 2 weeks post-injury. This finding was associated with a greater degree of white matter sparing at the lesion epicenter when cords were later sectioned and stained. Furthermore, treated animals were found to exhibit improved bladder function and a reduced incidence of hemorrhagic cystitis compared to control counterparts. Collectively these results demonstrate the neuroprotective potential of FTY720 treatment after experimental SCI.

Intraoperative anaphylactic shock in a child with no history of type I hypersensitivity.

Natural rubber latex is the second most implicated agent in intraoperative anaphylactic reactions. This report describes a case of intraoperative anaphylaxis occurring in a non-atopic fourteen-year-old girl undergoing multiple surgical procedures, but without spina bifida, in which latex surgical gloves were the main culprit for the anaphylactic reactions. Clinical manifestations of an anaphylactic reaction were also experienced during the examination of the possible cause of intraoperative anaphylaxis by skin prick testing with a latex allergen extract. Skin tests with anesthetics were negative. Specific IgE to latex was positive at 92.9 kUA/L (class 5). The molecular basis for the reported intraoperative anaphylaxis was ascribed to three low-molecular mass latex allergens (10-15 kD) detected in the brand of latex surgical gloves used during the operation. Given the potential of a dramatic outcome, latex allergy testing as a regular preoperative measure may contribute to the reduction of anaphylactic reactions during surgical interventions.

Antibodies to urinary tract pathogens in patients with spinal cord lesions.

Chronic or recurrent urinary tract infection (UTI) is a significant problem or patients with spinal cord lesions (SCL). UTIs are thought to be a major factor in the development of reduced renal function. To investigate the pathogenesis 151 patients with SCL were included in this study during a 7 year period. Results of intravenous pyelography and isotope renography were recorded as well as the bladder emptying methods. One to seven blood samples were obtained from each patient and tested for plasma creatinine, and the presence of precipitating antibodies against Escherichia coli, Klebsiella pneumonia, Klebsiella ozaenae, Proteus mirabilis, Enterococcus faecalis and Pseudomonas aeruginosa. We found significant correlation between duration of SCL and precipitating antibodies against urinary tract pathogens (PAU) (r = 0.23, P < 0.005), between plasma creatinine and PAU in patients with spina bifida (r = 0.64, P < 0.01), between PAU and the number of positive urine cultures (r = 0.17; P < 0.05) and a relation between abnormal urological findings and PAU. In addition, the PAU was significantly higher in patients with indwelling urethral catheters (P < 0.001). Thus it seems that PAU can be of prognostic value in SCL patients, and PAU might be an indicator for intensified treatment of recurrent UTI.

[Myelopathy associated with HTLV-1: clinical electrophysiologic study]. / Mielopatía asociada al HTLV-1: estudio clinicoelectrofisiológico.

Clinical and electrophysiological studies have been performed in 9 cases of HTLV-I associated myelopathy (7 female, 2 male). Spastic paraparesis and neurogenic bladder were present in 8; sensory disturbances were detected only in 4. The conduction velocities of the posterior tibial and sural nerves were reduced in 2 cases. Median nerve SSEP revealed a delay of N11, N13, N14, N20 peak latencies and an increase of N9-N20, N13-N14 and N13-N20 interpeak latencies. The electrophysiological studies are the most accurate indicators of the diffuse involvement not only of central motor and sensory pathways but also of the peripheral nervous system.

Degos' disease: radiological and immunological aspects.

We present an 18-year-old patient with Degos' disease who manifested the sudden onset of paraplegia. Neurological examination revealed a rt-hemianopsia, paraparesis (with a sensory level at Th12), and a neurogenic bladder. Brain MRI showed multiple cerebral infarctions accompanied by small hemorrhagic areas and GdDTPA enhancement of the dura. A cerebral angiogram displayed stenosis, ectasia, and aneurysms involving the peripheral branch of arteries. Stenoses also were observed in the celiac artery and small arteries in the 1t-kidney. Skin biopsy exhibited hyperkeratosis, atrophy of the epidermis, and necrobiosis of the collagen layer. Laboratory examinations disclosed persistent elevations of the thrombin-antithrombin III complex (TAT), plasmin-alpha 2 plasmin inhibitor complex (PIC), and cytotoxic T cell subset (CD8+CD11-), illustrating the coagulative, fibrinolytic, and immunological implications of this disease.