ArticleLiterature Review

Bladder dysfunction in peripheral neuropathies

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Abstract

Normal bladder function depends on the complex interaction of sensory and motor pathways. Bladder dysfunction can develop as a result of several neurological conditions. It can happen in a number of ways, including diabetic cystopathy, detrusor overactivity, bladder outlet obstruction, and urge and stress urinary incontinence. Diabetic neuropathy is the most common cause of peripheral neuropathy-associated bladder dysfunction. Guillain-Barré syndrome (GBS), human immunodeficiency virus (HIV)-associated neuropathy, chronic inflammatory demyelinating polyneuropathy (CIDP), and amyloid neuropathy are other major causes. The diagnosis of bladder dysfunction should be established by the history of neurological symptoms, neurological examination, and urological evaluation. Functional evaluation of the lower urinary tract includes cystometry, sphincter electromyography, uroflowmetry, and urethral pressure profilometry. Management of urinary symptoms in patients with bladder dysfunction is usually supportive. In some cases, alpha-blocker and/or anti-muscarinic agents are needed to help improve urinary dysfunction. Intermittent self-catheterization is needed occasionally for patients with slow and/or poor recovery.

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... The cause of bladder dysfunction in diabetes mellitus is primarily peripheral and autonomic neuropathy. Animal and human studies have revealed that diabetic cystopathy develops as a result of polyneuropathy, which predominantly affects sensory and autonomic nerve fibres [30] . ...
... Impaired bladder sensation is usually the first manifestation of lower urinary tract involvement. Micturition reflexes are delayed due to diminished bladder sensation with increases in bladder capacity and urinary retention that usually occur asymptomatically [26,30] . Patients are frequently unaware of bladder dysfunction until they have a urinary tract infection secondary to increased residual urine volume [3,26,30] . ...
... Micturition reflexes are delayed due to diminished bladder sensation with increases in bladder capacity and urinary retention that usually occur asymptomatically [26,30] . Patients are frequently unaware of bladder dysfunction until they have a urinary tract infection secondary to increased residual urine volume [3,26,30] . The common symptoms are straining, hesitation and weakness of stream [26,30] . ...
Article
Introduction: Changes in human behaviour and lifestyle over the last century have resulted in a dramatic increase in the incidence of diabetes worldwide. Neuropathy is a common and costly complication of both type 1 and type 2 diabetes. The prevalence of neuropathy is estimated to be about 8% in newly diagnosed patients and greater than 50% in patients with long-standing disease. There are two main types of diabetic neuropathies, named as sensorimotor and autonomic neuropathies. Sensorimotor neuropathy is marked by pain, paraesthesia and sensory loss, and autonomic neuropathy may contribute to myocardial infarction, malignant arrhythmia and sudden death. Methods: In this article we reviewed the pathogenesis, clinical manifestations diagnosis and treatment of diabetic neuropathies. Conclusion: Sensorimotor and autonomic neuropathies (cardiovascular, gastrointestinal and genitourinary autonomic neuropathies) are common in diabetic patients. Apart from strict glycaemic control, no further therapeutic approach exists in the prevention of this phenomenon. Intensive diabetes therapy, intensive multifactorial cardiovascular risk reduction and lifestyle intervention are recommended in patients with cardiovascular autonomic neuropathy. Gastroparesis is the most debilitating complication of gastrointestinal autonomic neuropathy and genitourinary autonomic neuropathy can cause sexual dysfunction and neurogenic bladder; these conditions are hard to manage. The symptomatic treatment of sensory symptoms includes tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors, gabapentin, pregabalin and opioids. Other treatment strategies are not so effective.
... In patients with diabetes and bladder dysfunction, sensory and autonomic nerve fibers areaffected [104]. Patients often remain asymptomatic in early stagesand impaired bladder sensation is usually the first manifestation of lower urinary tract involvement [1]. ...
... Patients often remain asymptomatic in early stagesand impaired bladder sensation is usually the first manifestation of lower urinary tract involvement [1]. The usual symptoms are straining, hesitation and weakness of stream [52,104]. Impaired sensation of bladder fullness leads to overstretched bladder, reduced bladder contractility, increased residual urine and impaireduroflow in the patients with diabetic bladder dysfunction [104]. ...
... The usual symptoms are straining, hesitation and weakness of stream [52,104]. Impaired sensation of bladder fullness leads to overstretched bladder, reduced bladder contractility, increased residual urine and impaireduroflow in the patients with diabetic bladder dysfunction [104]. ...
Article
Full-text available
Diabetic neuropathy is a common problem and can present various clinical presentations such as cranialneuropathy, radiculopathy, plexopathy, mononeuropathy, polyneuropathy and autonomic neuropathy. Clinicalevaluation and use of scoring systems for the evaluation of diabetic polyneuropathy is an important step to getcorrect diagnosis. New informations about the diagnosis of diabetic neuropathy continue to emerge, whichwill lead to correct diagnosis and treatment as well. Diabetic length-dependent sensorimotor polyneuropathy(DSPN) and carpal tunnel syndrome are the most common seen problems. While acute and painful situationswith motor weakness are mostly transient, sensory fibres are predominantly involved in chronic ones. Nerveconduction studies are needed to confirm diagnosis of any type of diabetic neuropathy, but they are normal incases with small fiber involvement. The early diagnosis is crucial because it is well-known that subclinicaldiabetic neuropathy may be reversed or significantly improved with diabetes control. Because neuropathy atthe stage in which only small fibers are affected can be reversed, it is important to diagnose DSPN in thesestages. Skin biopsy taken from the dermatomal area of sural nerve, laser-doppler-imager flare technique, cornealconfocal microscopy are used to assess small fibre dysfunction. The aim of the present review was to evaluateevidence-based diagnosis for any type of neuropathy seen in the patients with diabetes mellitus.
... The most common hereditary PN is Charcot-Marie-Tooth (CMT) disease. 44,64 ANS dysfunctions including reduced sweating, bladder dysfunction, impotence, fluctuations in blood temperature and BP, and repeated vomiting can be seen in hereditary sensory and autonomic neuropathies. 65 However, there is no clear information on prevalence and clinic features on cardiac involvement in hereditary peripheral neuropathy including CMT and hereditary sensory and autonomic neuropathies. ...
... In the familial form, the deposits are produced from abnormally folded transthyretin gene products (ATTR). 64 Regardless of differences in the substance of the amyloid deposit, small-fiber neuropathy is seen in Amyloid Light-chain and Transthyretin-related amyloidosis amyloidosis. Amyloid neuropathies are rare but well known. ...
Article
Cardiac autonomic neuropathy (CAN) is the least recognized and understood complication of peripheral neuropathy. However, because of its potential adverse effects including sudden death, CAN is one of the most important forms of autonomic neuropathies. CAN presents with different clinical manifestations including postural hypotension, exercise intolerance, fluctuation of blood pressure and heart rate, arrhythmia, and increased risk of myocardial infarction. In this article, the prevalence, clinical presentations, and management of cardiac involvement in certain peripheral neuropathies, including diabetic neuropathy, Guillain-Barré syndrome, chronic inflammatory polyneuropathy, human immunodeficiency virus-associated neuropathy, hereditary neuropathies, and amyloid neuropathy are examined in detail.
... Considering the intricate neural networks that regulate the LUT in health, it is not surprising that LUT dysfunction occurs following neurological disease. The pattern of LUT dysfunction is influenced by the level of neurological lesion (Table 1) [17][18][19][20][21][22]. ...
... Multiple sclerosis [19] Multiple system atrophy [20] Infrasacral lesion Hesitancy, retention Detrusor underactivity, sphincter insufficiency Cauda equina syndrome [21] Peripheral neuropathy [22] initiate voiding voluntarily. Patients often describe an interrupted urinary flow may not empty their bladder completely and resort to voiding a second time soon afterwards, known as double voiding. ...
Article
Full-text available
The lower urinary tract (LUT) in health is regulated by coordinated multi-level neurological inputs which require an intact central and peripheral nervous system. Lower urinary tract dysfunction is, therefore, a common sequelae of neurological disease and the patterns of bladder storage and voiding dysfunction depend upon the level of neurological lesion. Evaluation includes history taking, bladder diary, urological examination when relevant, ultrasonography and urodynamic testing when indicated. Antimuscarinic agents are the first line treatment for patients with storage dysfunction. Alternative treatments include intradetrusor injection of onabotulinumtoxinA, which has been shown to be of benefit in patients with neurogenic detrusor overactivity (NDO), and neuromodulation. Intermittent catheterization remains the option of choice in patients with significant voiding dysfunction resulting in high post-void residual volumes.
... Bladder dysfunction due to neuronal dysfunction involves complex and sophisticated interactions among the somatic and autonomic afferent and efferent pathways. Some studies have reported a close relationship between diabetesinduced peripheral neuropathy and bladder dysfunction [10]. This has been further confirmed by neuromodulation in the treatment of voiding dysfunction in diabetic rats [11]. ...
Article
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Dorsal root ganglion (DRG) neurons, which are sensitive to oxidative stress due to their anatomical and structural characteristics, play a complex role in the initiation and progression of diabetic bladder neuropathy. We investigated the hypothesis that the antioxidant and antiapoptotic effects of CGRP may be partly related to the expression of Nrf2 and HO-1, via the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, thus reducing apoptosis and oxidative stress responses. This study shows that CGRP activates the PI3K/AKT pathway, thereby inducing increased expression of Nrf2 and HO-1 and resulting in the decrease of reactive oxygen species and malondialdehyde levels and reduced neuronal apoptosis. These effects were suppressed by LY294002, an inhibitor of the PI3K/AKT pathway. Therefore, regulation of Nrf2 and HO-1 expression by the PI3K/AKT pathway plays an important role in the regulation of the antioxidant and antiapoptotic responses in DRG cells in a high-glucose culture model.
... It is the most prevalent and studied clinical presentation of diabetic neuropathy, accounting for 75% of all cases [4], with the strongest evidence for its pathogenesis, and is thus the focus of this review article. Other clinical presentations of diabetic neuropathy, such as autonomic neuropathies, acute painful-distal sensory polyneuropathies (hyperglycemia-or treatment-induced), focal or multifocal neuropathies, mononeuropathy, mononeuropathy multiplex, radiculoplexus neuropathy and entrapment neuropathies [5], are beyond the scope of this article; however, we refer the reader to relevant review articles [4,[6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Also, the pathogeneses of other linked diabetes-related complications, such as retinopathy, foot ulceration and Charcot neuropathic osteoarthropathy, are not discussed in this article. ...
Article
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Distal symmetrical polyneuropathy (DSPN) is a serious complication of diabetes associated with significant disability and mortality. Although more than 50% of people with diabetes develop DSPN, its pathogenesis is still relatively unknown. This lack of understanding has limited the development of novel disease-modifying therapies and left the reasons for failed therapies uncertain, which is critical given that current management strategies often fail to achieve long-term efficacy. In this article, the pathogenesis of DSPN is reviewed, covering pathogenic changes in the peripheral nervous system, microvasculature and central nervous system (CNS). Furthermore, the successes and limitations of current therapies are discussed, and potential therapeutic targets are proposed. Recent findings on its pathogenesis have called the definition of DSPN into question and transformed the disease model, paving the way for new research prospects.
... DU may be idiopathic in many cases, or may result from normal ageing processes, medication side-effects, or from another known cause of neurogenic, myogenic, or iatrogenic origin. 6,10,12,13 Neurogenic causes include Parkinson's disease, diabetic neuropathy, Guillane-Barre syndrome, multiple sclerosis, spinal-lumbar disk hernia or spinal cord injury, and other neuropathies 6,12,14,15 . Myogenic and circulatory factors include BOO, diabetes, heart disease, and chronic pelvic ischemia. ...
Article
Detrusor underactivity (DU) is an important contributor to lower urinary tract symptoms (LUTS). While DU has been defined in the literature in urodynamic terms, current definitions lack specific parameters. In addition, the clinical syndrome associated with and manifesting itself as DU, underactive bladder (UAB), has not been well defined in the literature. In the absence of a precise definition of UAB, it is difficult to appreciate the true nature and burden of this condition. We review the evidence regarding the epidemiology, pathogenesis, diagnosis, and treatment of DU and UAB and discuss the challenges in gathering data in the absence of precise definitions. DU may be idiopathic or caused by ageing, medications, or a number of causes of neurogenic, myogenic, or iatrogenic origin. Treatments are largely palliative due to a lack of curative options, and include watchful waiting, catheterization, medications, and surgical interventions. In light of the evidence available in the literature, we propose that a new symptom‐based definition of UAB syndrome should be developed as a first step in furthering more standardized research. Further discussion on this proposed definition to reach expert consensus will enable researchers to gather more robust data, allowing greater insights into DU and UAB diagnosis and treatment.
... Demographic characteristics, lesion characteristics, and functional independence were all identified as factors that might influence bladder management decisions [8,27]. Diabetes was included because, in some cases, it can lead to peripheral neuropathy that is severe enough to warrant catheterization [28]. The variable 'UTI before first bladder emptying assessment' was used to control for whether an early UTI had already influenced bladder emptying method at the first measurement point. ...
Article
Objective To understand the occurrence of and risk factors for urinary tract infections (UTIs) in patients with spinal cord injury (SCI) undergoing specialized SCI rehabilitation in Switzerland. Patients and Methods This study used data collected from 369 patients, who participated in a nationwide rehabilitation cohort for SCI in Switzerland between 2013 and 2017. Information on UTIs as well as their potential determinants, including demographics, lesion characteristics, and time‐updated data on functional independence and bladder management was used. Multivariable regression methods were applied to perform a time‐updated evaluation of determinants of UTI risk. Results The crude incidence rate (IR) of UTIs (95% confidence interval (CI)) was 0.55 (0.49 – 0.62) UTIs per 100 person‐days, cumulative incidence was 43%, median length of stay was 122 days. Bladder emptying method at discharge was largely determined by 28 days after admission. Among those using indwelling or assisted intermittent catheterisation, the likelihood of self‐intermittent catheterisation (IC) at discharge was positively related to level of self‐care independence, negatively to age at injury, and lower in females than males. Catheter users consistently had higher adjusted IRs of UTIs than spontaneous voiders, IR ratios (95% CI): indwelling catheter: 5.97 (2.63 – 13.57); assisted‐IC: 6.05 (2.63 – 13.94); self‐IC: 5.16 (2.31 – 11.52); test for differences across catheter groups: p=0.82. Lesion severity and previous UTI had additional but smaller effect sizes. Conclusions Bladder emptying method was identified as the main risk factor for UTI in patients with SCI. As spontaneous voiders have the lowest UTI rate, further research is warranted to reduce voiding dysfunction, for instance using neuromodulation procedures. This article is protected by copyright. All rights reserved.
... The management of bladder dysfunction in patients with hTTRA is discussed in depth elsewhere in this issue of Clinical Autonomic Research. In brief, a urodynamic study is helpful to evaluate parasympathetic and sympathetic dysfunction [4]. In bladder retention, micturition is recommended at a regular interval, while liquid intake should be reduced before nighttime. ...
Article
Full-text available
Purpose Hereditary transthyretin amyloidosis (hATTR) is a severe adult-onset progressive disease mainly involving the peripheral nervous system and the heart, with a prominent impact on the autonomic nervous system. This review summarizes the clinical aspects of autonomic dysfunction in hATTR, and their impact on quality of life as well as potential therapeutic options. Methods Literature review. Results Autonomic dysfunction, causing neurogenic orthostatic hypotension, gastroparesis, constipation, diarrhea, bladder dysfunction, and erectile dysfunction in males, has a major impact on the quality of life of patients with hATTR. Improvement of qualify of life in patients with hATTR implies periodic symptomatic screening and early management, taking into consideration comorbidities and medication side effects. The specific effect of the disease-modifying treatment on this aspect remains to be unraveled. Conclusions Management of autonomic dysfunction in patients with hAATR is feasible and can result in improved qualify of life. Novel disease-modifying treatments for hAATR may contribute to improve autonomic dysfunction, although specific studies are required.
... Various studies have identified age [1,10,11], vaginal childbirth [12,13] and obesity [14,15] as risk factors for PFDs. Other studies suggest that some PFDs are associated with diabetes [16], connective tissue disorders [17] and neurological diseases [18][19][20]. Some women have a genetic predisposition to the development of PFDs [21,22]. ...
Article
Childbirth is an important event in a woman's life. Vaginal childbirth is the most common mode of delivery and it has been associated with increased incidence of pelvic floor disorders later in life. In this article, the authors review and summarize current literature associating pelvic floor disorders with vaginal childbirth. Stress urinary incontinence and pelvic organ prolapse are strongly associated with vaginal childbirth and parity. The exact mechanism of injury associating vaginal delivery with pelvic floor disorders is not known, but is likely multifactorial, potentially including mechanical and neurovascular injury to the pelvic floor. Observational studies have identified certain obstetrical exposures as risk factors for pelvic floor disorders. These factors often coexist in clusters; hence, the isolated effect of these variables on the pelvic floor is difficult to study.
... Even in patients with stable glycemic control, the incidence of DCP is still as high as 25% 1 . Patients with DCP mainly present with symptoms such as low bladder detrusor contractility and decreased urination sensation, which eventually causes chronic urinary retention and full urinary incontinence 2,3 . ...
Article
Full-text available
This study aimed to explore the effect of calcitonin gene-related peptide (CGRP) on bladder smooth muscle cells (BSMCs) under high glucose (HG) treatment in vitro. BSMCs from Sprague–Dawley rat bladders were cultured and passaged in vitro. The third-generation cells were cultured and divided into control group, HG group, HG + CGRP group, HG + CGRP + asiatic acid (AA, p-p38 activator) group, CGRP group, AA group, HG + CGRP + CGRP-8-37 (CGRP receptor antagonist) group and HG + LY2228820 (p38 MAPK inhibitor) group. The cell viability, apoptosis, malondialdehyde (MDA) and superoxide dismutase (SOD) levels of BSMCs were observed by the relevant detection kits. The expressions of α-SM-actin, p38 and p-p38 were detected by qRT-PCR or Western blot analysis. Compared with the control group, the cell viability, SOD and α-SM-actin levels of BSMCs were decreased and apoptotic cells, MDA and p-p38 levels were increased after HG treatment, while these changes could be partly reversed when BSMCs were treated with HG and CGRP or LY2228820 together. Moreover, AA or CGRP-8-37 could suppress the effect of CGRP on BSMCs under HG condition. Our data indicate that CGRP protects BSMCs from oxidative stress induced by HG in vitro, and inhibit the α-SM-actin expression decrease through inhibiting the intracellular p38 MAPK signaling pathway.
... Gradual progression of both motor and sensory deficit leads to the impairment of locomotion and balance. In the last two decades, studies have documented autonomic nervous system (ANS) dysfunction being associated with later stages of CMT disease (9). The pupilary abnormalities related to late onset axonal neuropathy caused by MPZ gene mutation (Glu97Val) and most frequently in CMT type 2 caused by different gene mutations were reported (10,11). ...
Article
Full-text available
To evaluate lower urinary tract (LUT), bowel, and sexual dysfunctions in a series of patients with Charcot-Marie-Tooth disease (CMT). A cohort of 58 patients and 54 healthy controls filled out the International Prostate Symptoms Score (IPSS) and the International Consultation on Incontinence Modular (ICIQ) Questionnaires to assess their symptoms and their impact on the patient's quality of life. On the IPSS questionnaire, CMT patients reported a significantly higher score compared with the healthy controls in 7 of 8 questions. The ICIQ-male LUT symptoms questionnaire revealed a significantly higher score in 7 of 26 questions. In the ICIQ-female LUT questionnaire, a significantly higher score was observed in 13 of 24 questions. When assessing the bowel function in CMT patients using the ICIQ-bowel questionnaire, a significantly higher score in 30 of 40 questions was noted. No differences in sexual function were found in either group. The occurrence of the LUT symptoms and bowel dysfunctions in CMT patients was significantly higher when compared with an age-matched control group. The symptoms were more frequent in female patients. The findings suggest that autonomic dysfunction should be evaluated and included in the diagnostic approach and care of CMT patients.
... For that reason, scheduled voiding and the Crede maneuver should be incorporated early on as part of the behavioral therapy recommended for patients [44]. If primary methods fail, scheduled self-catheterization may be required [45]. ...
Article
The immunoglobulin light-chain amyloidosis is a multisystemic disease which manifests by damage to the vital organs by light chain-derived amyloid fibril. Traditionally, the treatment has been directed to the underlying plasma cell clone with or without high dose chemotherapy followed by autologous stem cell transplantation using melphalan based conditioning. Now with the approval of highly tolerable anti-CD38 monoclonal antibody daratumumab based anti-plasma cell therapy in 2021, high rates of hematologic complete responses are possible even in patients who are otherwise deemed not a candidate for autologous stem cell transplantation. However, despite the progress, there remains a limitation in the strategies to improve symptoms particularly in patients with advanced cardiac involvement, those with nephrotic syndrome and autonomic dysfunction due to underlying systemic AL amyloidosis. The symptoms can be an ordeal for the patients and their caregivers and effective strategies are urgently needed to address them. The supportive care is aimed to counteract the symptoms of the disease and the effects of the treatment on involved organs' function and preserve patients' quality of life. Here we discuss multidisciplinary approach in a system-based fashion to address the symptom management in this dreadful disease. In addition to achieving excellent anti-plasma cell disease control, using treatment directed to remove amyloid from the vital organs can theoretically hasten recovery of the involved organs thereby improving symptoms at a faster pace. Ongoing phase III clinical trials of CAEL-101 and Birtamimab will address this question.
... The gradual progression of motor and sensory impairment leads to compromised locomotion and balance as well as dysfunction of the ANS. 6 ANS dysfunction can lead to hyperactivity of the detrusor muscle, with symptoms of urinary urgency with or without urge incontinence, accompanied by nocturia and an increase in urinary frequency. 7 Clinical practice guidelines recommend pelvic floor muscle training (PFMT) as first-line treatment for SUI and mixed urinary incontinence in women (level A scientific evidence). ...
Article
Objective The purpose of this report is to describe the effects of pelvic floor muscle training (PFMT) in stress urinary incontinence (SUI) of a woman with Charcot-Marie-Tooth (CMT) disease. Clinical Features A 50-year-old female patient with a diagnosis of type II CMT disease was referred to treatment as a result of a complaint of urinary loss upon effort (ie, coughing and sneezing). She reported that the symptoms started about 36 months prior. The urodynamic study revealed SUI with a Valsalva leak point pressure of 84 cmH2O. Intervention and Outcome The treatment of SUI was carried out through a PFMT program for 12 weeks (with supervision) and exercises at home for another 12 weeks. A specialized physiotherapist measured symptoms and severity of SUI (3-day urinary diary, 1-hour pad test), pelvic floor muscle function (digital palpation, manometry and dynamometry), effect of the SUI on quality of life (Incontinence Quality of Life Questionnaire), and adherence to the outpatient sessions and to home exercise sets, which also were assessed (exercise diary). Conclusion In this patient with CMT disease, improvements in urinary symptoms and severity of SUI, pelvic floor muscle function, and effect of SUI on quality of life were noted after PFMT.
Article
Background and purpose: Spinal voltage-gated calcium channels (VGCCs) are pivotal regulators of painful and inflammatory alterations, representing attractive therapeutic targets. We examined the effects of epidural administration of the P/Q- and N-type VGCC blockers Tx3-3 and Phα1β, respectively, isolated from the spider Phoneutria nigriventer, on symptomatic, inflammatory and functional changes allied to mouse cyclophosphamide (CPA)-induced haemorrhagic cystitis (HC). The effects of P. nigriventer-derived toxins were compared with those displayed by MVIIC and MVIIA, extracted from the cone snail Conus magus. Experimental approach: HC was induced by a single i.p. injection of CPA (300 mg·kg(-1) ). Dose- and time-related effects of spinally administered P/Q and N-type VGCC blockers were assessed on nociceptive behaviour and macroscopic inflammation elicited by CPA. The effects of toxins were also evaluated on cell migration, cytokine production, oxidative stress, functional cystometry alterations and TRPV1, TRPA1 and NK1 receptor mRNA expression. Key results: The spinal blockage of P/Q-type VGCC by Tx3-3 and MVIIC or N-type VGCC by Phα1β attenuated nociceptive and inflammatory events associated with HC, including bladder oxidative stress and cytokine production. CPA produced a slight increase in bladder TRPV1 and TRPA1 mRNA expression, which was reversed by all the toxins tested. Noteworthy, Phα1β strongly prevented bladder neutrophil migration, besides HC-related functional alterations, and its effects were potentiated by co-injecting the selective NK1 receptor antagonist CP-96345. Conclusions and implications: Our results shed new light on the role of spinal P/Q and N-type VGCC in bladder dysfunctions, pointing out Phα1β as a promising alternative for treating complications associated with CPA-induced HC.
Article
Background and purpose: Drug-induced arrhythmia due to blockade of the Kv 11.1 channel (also known as the hERG K(+) channel) is a frequent side effect. Previous studies have primarily focused on equilibrium parameters, i.e. affinity or potency, of drug candidates at the channel. The aim of this study was to determine the kinetics of the interaction with the channel for a number of known Kv 11.1 blockers and to explore a possible correlation with the affinity or physicochemical properties of these compounds. Experimental approach: The affinity and kinetic parameters of 15 prototypical Kv 11.1 inhibitors were evaluated in a number of [(3) H]-dofetilide binding assays. The lipophilicity (logKW - C8 ) and membrane partitioning (logKW - IAM ) of these compounds were determined by means of HPLC analysis. Key results: A novel [(3) H]-dofetilide competition association assay was set up and validated, which allowed us to determine the binding kinetics of the Kv 11.1 blockers used in this study. Interestingly, the compounds' affinities (Ki values) were correlated to their association rates rather than dissociation rates. Overall lipophilicity or membrane partitioning of the compounds were not correlated to their affinity or rate constants for the channel. Conclusions and implications: A compound's affinity for the Kv 11.1 channel is determined by its rate of association with the channel, while overall lipophilicity and membrane affinity are not. In more general terms, our findings provide novel insights into the mechanism of action for a compound's activity at the Kv 11.1 channel. This may help to elucidate how Kv 11.1-induced cardiotoxicity is governed and how it can be circumvented in the future.
Article
Detrusor underactivity (DUA) is defined as a voiding contraction of reduced strength and/or duration, which prolongs urination and/or prevents complete emptying of the bladder within a 'normal' period of time. This issue is associated with voiding and postmicturition urinary symptoms, and can predispose to urinary infections and acute urinary retention. The aetiology of DUA is influenced by multiple factors, including ageing, bladder outlet obstruction, neurological disease, and autonomic denervation. The true prevalence of this condition remains unknown, as most data come from referral populations. Urodynamic testing is used to diagnose the condition, either by assessing the relationship between bladder pressures and urinary flow, or by interrupting voiding to measure detrusor pressure change under isovolumetric conditions. Current treatments for DUA have poor efficacy and tolerability, and often fail to improve quality of life; muscarinic receptor agonists, in particular, have limited efficacy and frequent adverse effects. Bladder emptying might be achieved through Valsalva straining, and intermittent or indwelling catheterization, although sacral nerve stimulation can reduce dependency on catheterization. Novel stem-cell-based therapies have been attempted; however, new drugs that increase contractility are currently largely conceptual, and the complex pathophysiology of DUA, difficulty achieving organ specificity of treatment, the limited availability of animal models, and the subjective nature of current outcome measures must be addressed to facilitate the development of such agents.
Article
Guillain Barre syndrome (GBS) is a kind of nervous system disease, which is characterized by different extent of injuries on nerve roots. The exact etiopathogenisis is not clear. But most studies proved that GBS is a kind of autoimunne disease. Acute GBS is regarded as major symptom in clinical GBS. According to the injuring parts of nerve roots, Acute GBS is devided into different subtypes. This article mainly review that in humoral immune reaction, IgG antibodies can attack different constituents on myelin and axon (such as neuroglian, nerofascin and ganglioside), resulting in the disturbance of nerve conduction, inducing different subtypes of acute Guillain Barre.
Article
Diabetes mellitus is the commonest cause of an autonomic neuropathy in the developed world. Diabetic autonomic neuropathy causes a constellation of symptoms and signs affecting cardiovascular, urogenital, gastrointestinal, pupillomotor, thermoregulatory, and sudomotor systems. Several discrete syndromes associated with diabetes cause autonomic dysfunction. The most prevalent of these are: generalized diabetic autonomic neuropathy, autonomic neuropathy associated with the prediabetic state, treatment-induced painful and autonomic neuropathy, and transient hypoglycemia-associated autonomic neuropathy. These autonomic manifestations of diabetes are responsible for the most troublesome and disabling features of diabetic peripheral neuropathy and result in a significant proportion of the mortality and morbidity associated with the disease.
Thesis
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This thesis examined how and why TRPV1 function is being modulated in sensory neuropathy and explored the potential of its rescue in the urinary bladder of STZ-­‐induced diabetic rats. Diabetes induced a rapid decline in TRPV1 function and changes in neurogenically mediated electrically-­‐evoked responses together with a gradual decline in muscarinic function. Diabetic bladder was also deficient in muscarinic and TRPV1 organ bath temperature-­‐induced changes but not in those affecting spontaneous contractile activity. Exposure to a potential neuropathy causative agent, methylglyoxal was studied and its mechanism of action explored through the use of TRPA1 ligands. Methylglyoxal exposure mimicked some of the effects of diabetes on TRPV1, neurogenic electrically evoked responses and muscarinic function. Methylglyoxal effects were seen to be partly through TRPA1 receptor activation but other as yet undefined pathways were also involved. Use of TRPA1 ligands revealed an unexpected complexity of the interaction of the TRPA1 receptor with TRPV1. Finally the potential of reversing the diminished TRPV1 response was examined through the use of three known sensitising agents, bradykinin, NGF and insulin. Bradykinin was the only agent seen to reverse the TRPV1 diminished response back up to to control equivalent levels and through the use of bradykinin selective ligands, it was seen that the dual activation of BK-­‐1 and BK-­‐2 receptor was necessary to rescue the TRPV1 response. The likely mechanism of action of bradykinin was through prostaglandin production as indomethacin blocked TRPV1 rescue. In the acute stage of diabetes, TRPV1 function is downregulated and may be caused by exposure to a neuropathy-­‐causing metabolite such as methylglyoxal. The TRPV1 function still retains plasticity at this acute stage because function could be enhanced back to control levels by bradykinin receptor activation : a potential for early therapeutic intervention.
Article
The prevalence of lower urinary tract (LUT) dysfunction in peripheral nervous system (PNS) disorders is larger than in comparable control populations. This is particularly true for polyneuropathies with autonomic nervous system involvement, and for localized lesions with LUT innervation. LUT symptoms may be the guide to the diagnosis of processes localized in the lumbosacral spinal canal (as in cauda equina syndrome), and in the pelvis. Typical LUT dysfunctions (LUTD) caused by PNS involvement include bladder and sphincter hypoactivity with poor emptying, and incontinence. Paradoxically, bladder overactivity may also occur in pure PNS lesions. The acute cauda equina syndrome is an emergency requiring magnetic resonance imaging and surgery; in chronic neurogenic LUTD due to PNS involvement, the diagnosis of the lesion may be clarified by clinical neurophysiologic testing. Other important causes of neurogenic LUT dysfunction are perineoabdominal and pelvic surgeries. Surgeons are devising nerve-sparing techniques to prevent such major and often persistent complications in patients who are otherwise cured of the underlying disease. LUTD significantly affects the quality of life in patients and may lead to recurring urinary infections and upper urinary tract involvement. Thorough assessment of LUT function by urodynamics may be necessary in patients who are not improved by simple conservative measures. © 2015 Elsevier B.V. All rights reserved.
Article
Die diabetische Neuropathie ist eine der häufigsten und schwerwiegendsten Komplikationen des Diabetes mellitus. Sensorische Ausfälle, infizierte Fußulzera und Schäden an autonomen Nerven rauben Betroffenen oft viele Jahre Lebenserwartung. Daher ist von Anfang an Aufmerksamkeit gefragt. Neuropathische Schmerzen haben 10–20% der Diabetespatienten. Hier gilt es, den Schmerzcharakter herauszuarbeiten und geeignete Medikamente individuell zu titrieren.
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Autonomic nerve fibers are affected in most generalized peripheral neuropathies. Although this involvement is often mild or subclinical, there are a group of peripheral neuropathies in which the small or unmyelinated fibers are selectively or prominently targeted. These include the autonomic neuropathies associated with diabetes and amyloid, immune-mediated autonomic neuropathies including those associated with a paraneoplastic syndrome, inherited autonomic neuropathies, autonomic neuropathies associated with infectious diseases, and toxic autonomic neuropathies. The presenting features include impairment of cardiovascular, gastrointestinal, urogenital, thermoregulatory, sudomotor, and pupillomotor function. The accurate diagnosis of the autonomic neuropathies has been enhanced by the availability of physiological tests that measure autonomic function, and more recently, structural studies of the autonomic cutaneous innervation. With the help of these investigations and the judicious use of laboratory testing, many autonomic neuropathies can be accurately diagnosed and their clinical progression monitored.
Article
Diabetes mellitus is a chronic metabolic disease, posing a considerable threat to global public health. Treating systemic comorbidities has been one of the greatest clinical challenges in the management of diabetes. Diabetic bladder dysfunction, characterized by detrusor overactivity during the early stage of the disease and detrusor underactivity during the late stage, is a common urological complication of diabetes. Oxidative stress is thought to trigger hyperglycaemia-dependent tissue damage in multiple organs; thus, a growing body of literature has suggested a possible link between functional changes in urothelium, muscle and the corresponding innervations. Improved understanding of the mechanisms of oxidative stress could lead to the development of novel therapeutics to restore the redox equilibrium and scavenge excessive free radicals to normalize bladder function in patients with diabetes.
Article
Objectives: Diabetic cystopathy (DCP), characterized by peripheral neuropathy-associated bladder dysfunction, is a common urinary complication in patients with diabetes (~80%). Bone marrow mesenchymal stem cell (BMMSC) transplantation, a new and emerging regenerative therapy, provides a curative option for DCP. However, the application of this therapy is limited by the low survival rate and engraftment of transplanted stem cells. This study was undertaken to determine whether integrin-linked kinase (ILK) overexpression would improve stem cell survival and engraftment after BMMSC transplantation. Methods: Diabetes was induced in rats by injection of streptozotocin. ILK expression was detected by qRT-PCR and Western blot. Bladder function was measured by urodynamic analyses. Smooth-muscle regeneration and vascularization were evaluated by immunohistochemistry staining. Results: ILK overexpression by adenovirus promotes proliferation of BMMSCs in vitro. ILK overexpression enhanced the ability of BMMSCs to decrease the volume threshold for micturition and residual urine in the rats with diabetes. The contractile response of bladder strips, tissue structure of bladder and smooth-muscle regeneration/vascularization were also improved in the rats receiving ILK-modified BMMSCs. Conclusions: Our data highlight the clinical potential of transplantation of gene-modified BMMSCs in the treatment of DCP, thereby serving as a rapid and effective first-line strategy to cure the bladder dysfunction resulting from long-term diabetes.
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Aims: To investigate the link between lower urinary tract symptoms (LUTS) and metabolic disorders. Materials and methods: This report results from presentations and subsequent discussions about LUTS and metabolic disorders at the International Consultation on Incontinence Research Society (ICI-RS) in Bristol, 2014. Results: There are common pathophysiological determinants for the onset of LUTS and the metabolic syndrome (MetS). Both conditions are multifactorial, related to disorders in circadian rhythms and share common risk factors. As in men with erectile dysfunction, these potentially modifiable lifestyle factors may be novel targets to prevent and treat LUTS. The link between LUTS and metabolic disorders is discussed by using sleep, urine production and bladder function as underlying mechanisms that need to be further explored during future research. Conclusion: Recent findings indicate a bidirectional relationship between LUTS and the MetS. Future research has to explore underlying mechanisms to explain this relationship, in order to develop new preventive and therapeutic recommendations, such as weight loss and increasing physical activity. The second stage is to determine the effect of these new treatment approaches on the severity of LUTS and each of the components of the MetS.
Article
Urinary incontinence is a common problem that is often under-reported due to the embarrassing nature and social stigma attached. Urinary incontinence can have a considerable effect on an individual's quality of life, but can be significantly improved with correct assessment, treatment and management. Conservative treatment options, including pelvic floor exercises, bladder retraining and fluid modification, are recommended before referral to secondary services. This article provides an overview of the main types of urinary incontinence, and summarises recent guidelines for the assessment, diagnosis and effective conservative treatment options for them, and when a referral to specialist care is required.
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Practice nurses need to find out about all the different types of urinary incontinence and how they can be treated, before they can offer help to patients showing symptoms, writes Alison Bardsley Urinary incontinence is a common problem that is often under-reported due to the embarrassing nature and social stigma attached. Urinary incontinence can have a considerable effect on an individual's quality of life, but can be significantly improved with correct assessment, treatment and management. Conservative treatment options, including pelvic floor exercises, bladder retraining and fluid modification, are recommended before referral to secondary services. This article provides an overview of the main types of urinary incontinence, and summarises recent guidelines for the assessment, diagnosis and effective conservative treatment options for them, and when a referral to specialist care is required.
Article
Diabetic bladder dysfunction affects almost half of all diabetic patients, making it one of the most common complications of diabetes mellitus. The clinical presentation of diabetic bladder dysfunction can be varied and may be extremely bothersome to patients, negatively impacting their quality of life. Despite this, it remains understudied and under-represented in the medical literature. This review summarizes the current literature on pathophysiology, clinical presentation, urodynamic findings, evaluation, and management. Through this, we hope to provide guidance to clinicians involved with the management of this condition.
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Changes in environmental and behavioral factors such as a sedentary life style and obesity over the previous years have resulted in a dramatic increase in the incidence of diabetes worldwide [1]. Urological manifestations of Diabetic patients include: Diabetic Nephropathy, Renal Vascular disease, Urinary Tract Infections, Emphysematous Complications, Infertility, Erectile dysfunction, and Diabetic bladder dysfunction which we will talk about it in details in this section [2, 3].
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Objectives: To investigate the effectiveness of Chinese herbal medicine for the treatment of urinary incontinence in patients with chronic obstructive pulmonary disease. Methods: We carried out a retrospective cohort study using the National Health Insurance Research Database. From a cohort of 1 million records between 1996 and 2013, a total of 202 279 patients with newly onset chronic obstructive pulmonary disease were initially recruited. We matched with propensity score 3967 patients who received Chinese herbal medicine by age, sex, year of chronic obstructive pulmonary disease diagnosis, urbanization, comorbidities and chronic obstructive pulmonary disease medications. All participants received follow-up visits until the end of 2013 to record the incidence rate of urinary incontinence. The Cox proportional hazards model was applied to assess the association between Chinese herbal medicine use and the risk of urinary incontinence among chronic obstructive pulmonary disease patients. Results: The incidence rates of urinary incontinence were 57.33 and 108.15 (per 10 000 person-years) in the Chinese herbal medicine and non-Chinese herbal medicine cohorts, respectively, showing a significantly lower risk of urinary incontinence in Chinese herbal medicine users (aHR = 0.56, 95% CI = 0.45-0.69, P < 0.001). The Chinese herbal medicine prescription pattern analysis showed that Fritillariae thunbergii bulbus (Zhebeimu), Semen armeniacae amarum (Kuxingren), Platycodonis radix (Jiegeng), Xiao Qing Long Tang and Ding Chuan Tang constituted the core of Chinese herbal medicine prescriptions applied to treat chronic obstructive pulmonary disease. Conclusion: The use of Chinese herbal medicine in chronic obstructive pulmonary disease patients can reduce their risk of urinary incontinence.
Article
Neuropathy, or damage to the nerves of the peripheral nervous system, is a debilitating yet surprisingly common and complex condition. Diabetic peripheral neuropathy (DPN) is a prevalent, disabling condition. The damage of the central or peripheral nervous system results in neuropathic pain and which is also triggered by primary lesion and dysfunction of the nerves system. There is still limited knowledge about the factors that initiate and maintain neuropathic pain. It poses a significant challenge for clinicians as it is often diagnosed late when patients present with advanced consequences. The chronic hyperglycaemia activates various downsream cascasdes like polyol pathway, increasing glycation in non-enzymatic with several structural proteins that further alter Protein Kinase C activity, increases oxidative stress as well as alteration in Peroxisome proliferator-activated receptor gamma (PPAR-γ) activation that all are interrelated for the development and cause of neuropathy. Multifactorial risk factor reduction, targeting glycaemia, blood pressure and lipids can reduce the progression of DPN. Different therapies are also used for managing diabetic neuropathy and neuropathic pain includes anticonvulsants, opioids, antidepressants, aldose reuptake inhibitors. The current treatment of DPN is largely symptomatic. A number of novel potential candidates, including erythropoietin analogues, angiotensin II receptor type 2 antagonists, and sodium channel blockers are currently being evaluated in phase II clinical trials. Future studies are needed to further explore this relationship with implications for new treatments for this common disease.
Article
Light chain amyloidosis is a disease in which clonal plasma cells produce toxic immunoglobulin light chains that form amyloid fibrils with deposition in organs, most commonly the heart and kidneys, but also the nervous system, gastrointestinal tract, and soft tissues. Treatment directed at the clonal cells eliminates light chain production and further deposition and may enable organ improvement and decrease the risk of organ failure. Supportive care manages the symptoms of organ involvement and the side effects of treatment. Supportive care also addresses the psychological and social issues that may arise in patients with light chain amyloidosis.
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Small fiber neuropathy (SFN) is a disorder of the small myelinated Aδ-fibers and unmyelinated C-fibers [5, 6]. SFN might affect small sensory fibers, autonomic fibers or both, resulting in sensory changes, autonomic dysfunction or combined symptoms [7]. As a consequence, the symptoms are potentially numerous and have a large impact on quality of life [8]. Since diagnostic methods for SFN are numerous and its pathophysiology complex, this extensive review focusses on categorizing all aspects of SFN as disease and its diagnosis. In this review, sensitivity in combination with specificity of different diagnostic methods are described using the areas under the curve. In the end, a diagnostic work-flow is suggested based on different phenotypes of SFN.
Article
Aims Small fiber neuropathy/polyneuropathy (SFN) has been found to be present in 64% of complex (refractory or multisystem) chronic pelvic pain (CPP) patients. The small fiber dysfunction seen in SFN can negatively impact autonomic control of micturition in addition to pain. This study investigated the clinical association of autonomic dysfunction (detrusor underactivity and primary bladder neck obstruction [BNO]) on video urodynamics (VUDS) with SFN in patients with CPP. Methods This was a retrospective observational study, querying data from patients with complex CPP. Inclusion criteria were: the presence of complex (refractory or multisystem) CPP, and completion of both (1) subspecialty autonomic neurology evaluation for SFN and (2) high-quality VUDS performed according to ICS standards. Autonomic bladder dysfunction (BNO or detrusor underactivity) on VUDS was compared to the presence of SFN. Results Thirty-two female patients with complex CPP met criteria. Of the 32, 23 (72%) were found to have SFN. Patient with autonomic bladder dysfunction (BNO or detrusor underactivity) were more likely to have SFN (OR = 9.5 [95% CI: 1.641, 55.00], p = 0.007). Post-void residual volume was higher in the SFN group (p = 0.011 [95% CI: 13.12, 94.0]) and symptoms of urge urinary incontinence were more likely to be present (p = 0.000 [95% CI: −3.4, −1.25]). Conclusions Patients with complex CPP with autonomic bladder dysfunction are more likely to have SFN. This suggests patients with complex CPP should be considered for diagnosis and treatment of SFN, particularly if BNO or detrusor underactivity is noted on VUDS evaluation.
Article
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is the most common autoimmune neuropathy. The diagnosis depends on the clinical presentation with a progressive or relapsing course over at least 2 months and electrophysiological evidence of primary demyelination. Whereas typical CIDP is quite easily recognizable because virtually no other neuropathies present with both distal and proximal motor and sensory deficit, atypical CIDP, focal and multifocal variants in particular, may represent a difficult diagnostic challenge. CIDP very likely is an underdiagnosed condition as suggested also by a positive correlation between prevalence rates and sensitivity of electrophysiological criteria. Since no 'gold standard' diagnostic marker exists, electrophysiological criteria have been optimized to be at the same time as sensitive and as specific as possible. Additional supportive laboratory features, such as increased spinal fluid protein, MRI abnormalities of nerve segments, and in selected cases nerve biopsy lead to the correct diagnosis in the large majority of the cases. Objective clinical improvement following immune therapy is also a useful parameter to confirm the diagnosis. The pathogenesis and pathophysiology of CIDP remain poorly understood, but the available evidence for an inflammatory origin is quite convincing. Steroids, intravenous immunoglobulin (IVIG), and plasma exchange (PE) have been proven to be effective treatments. IVIG usually leads to rapid improvement, which is useful in severely disabled patients. Repeat treatment over regular time intervals for many years is often necessary. The effect of steroids is slower and the side-effect profile may be problematic, but they may induce disease remission more frequently than IVIG. An important and as of yet uncompletely resolved issue is the evaluation of long-term outcome to determine whether the disease is still active and responsive to treatment.
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Maintenance of normal lower urinary tract function is a complex process that requires coordination between the central nervous system and the autonomic and somatic components of the peripheral nervous system. This article provides an overview of the basic principles that are recognized to regulate normal urine storage and micturition, including bladder biomechanics, relevant neuroanatomy, neural control of lower urinary tract function, and the pharmacologic processes that translate the neural signals into functional results. Finally, the emerging role of the urothelium as a sensory structure is discussed.
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To examine the prevalence and mechanism of urinary dysfunction in GBS. Urinary symptoms were observed and neurological examinations made repeatedly during hospitalization of 65 consecutive patients with clinico-neurophysiologically definite GBS. The patients included 41 men, 24 women; mean age, 41 years old; mean Hughes motor grade, 3; AIDP, 28, AMAN, 37. Urodynamic studies consisted of uroflowmetry, measurement of post-micturition residuals, medium-fill water cystometry, and external anal sphincter electromyography. Urinary dysfunction was observed in 27.7% of GBS cases (urinary retention, 9.2%). Urinary dysfunction was related to the Hughes motor grade (P < 0.05), defecatory dysfunction (P < 0.05), age (P < 0.05), and negatively related to serum IgG class anti-ganglioside antibody GalNAc-GD1a (P < 0.05). Urinary dysfunction was more common in AIDP (39%) than in AMAN (19%). No association was found between antibody titer against neuronal nicotinic acetylcholine receptors and urinary dysfunction. Urodynamic studies in nine patients, mostly performed within 8 weeks after disease onset, revealed post-void residual in 3 (mean 195 ml), among those who were able to urinate; decreased bladder sensation in 1; detrusor overactivity in 8; low compliance in 1; underactive detrusor in 7 (both overactive and underactive detrusor in 5); and nonrelaxing sphincter in 2. In our series of GBS cases, 27.7% of the patients had urinary dysfunction, including urinary retention in 9.2%. Underactive detrusor, overactive detrusor, and to a lesser extent, hyperactive sphincter are the major urodynamic abnormalities. The underlying mechanisms of urinary dysfunction appear to involve both hypo- and hyperactive lumbosacral nerves. Neurourol. Urodynam. 28:432-437, 2009. (c) 2009 Wiley-Liss, Inc.
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Eight of 32 patients (25%) with chronic inflammatory demyelinating polyneuropathy (CIDP) had micturitional disturbance, which consisted of voiding difficulty (n = 4), urgency (n = 4), or urgency incontinence (n = 1). Urodynamic studies on four symptomatic patients showed disturbed bladder sensation in two, bladder areflexia in one, and neurogenic changes of the external sphincter in one, indicative of peripheral parasympathetic and somatic nerve dysfunctions. Cystometry also showed detrusor overactivity in two patients but no evidence of CNS involvement, evidence that bladder overactivity occurs by probable pelvic nerve irritation.
Article
An electrophysiological method has been developed to test the structural integrity and function of the reflex arcs concerned with micturition. The technique has been used to delineate neuropathic involvement of the lower urinary tract.
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[OBJECTIVE] Voiding dysfunction in diabetic patients commonly develops insidiouly and urodynamic test is necessary to diagnose it. Since the measurement of nerve conduction velosity was simple test and eligible for screening of diabetic neuropathy, this study was focused to clarify if this test also could screen patients who have voiding dysfunction among diabetic patients. [MATERIALS AND METHODS] Uroflowmetry, water cystometry, symptom score(IPSS) and nerve conduction velocity were analyzed in 27 diabetic patients (20 males and 7 females, age ranged from 13 to 78 with a mean of 58.6). Nerve conduction velocity was measured for sensory nerve conduction velocity(SCV) of sural nerve and motor nerve conduction velocity(MCV) of peroneal nerve. Normal voiding was defined as continuous flow with the flow rate above -2SD on nomogram(Siroky's) and residual urine less than 50ml. Patients who did not full fil this criteria are considered to have voiding disorder. [RESULTS] Nine Of 27 patients(33%) showed voiding disorder. Vesical denervation supersensitivity test was negative in all patients(Lapides,1962). Mean IPSS was not significantly different between patienrs with or without normal voiding(8.0 vs 8.9), suggesting symptom alone does not predict underlying voiding dysfunction. Maximal vesical capasity over 500ml and first desire of voiding at over 300ml were observed more frequently in patients with abnormal SCV than those with normal SCV : 9/12 vs 1/15 (p<0.001) and 9/12 vs 4/15 (p<0.03), respectively. Nine of 14 patients with abnormal MCV showed voiding disorder while all patients with normal MCV showed normal voiding(p<0.001). [CONCLUSION] 1) Lower urinary tract symptom alone cannot predect diabetic vesicourethral dysfunction. 2) Nerve conduction velocity was demonstrated a valuable test which could screen a subclass of diabetic patients with voiding dysfunction.
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Article abstract-Objectives: To determine the character, intensity and frequency of pain in Guillain-Barre syndrome (GBS) and to evaluate the response to treatment. Design: A prospective longitudinal study. Setting: Academic hospital-based practices. Patients: Fifty-five consecutive patients with GBS. Interventions: Patients were evaluated on admission and at 2, 4, 8, 16, and 24 weeks. Main outcome measures: Character of pain, pain intensity using Visual Analogue Scale ([VAS] 0 to 10 cm) and Present Pain Intensity of McGill Pain Questionnaire, pain relief (VAS 0 to 10 cm), Disability Grading Scale for GBS. Results: Forty-nine patients (89.1%) described pain during the course of their illness. On admission, mean pain intensity (VAS) was 4.7 +/- 3.3. However, 26 patients (47.3%) described pain that was either distressing, horrible, or excruciating (mean VAS, 7.0 +/- 2.0). The most common pain syndromes observed were deep aching back and leg pain and dysesthetic extremity pain. Pain intensity on admission correlated poorly with neurologic disability on admission (r = 0.26, p = 0.06) and throughout the period of study (r < 0.20, p > 0.10). Forty-one patients (74.5%) required opioid analgesics, with 16 (29.0%) receiving parenteral morphine to provide adequate pain relief. Conclusions: Moderate to severe pain is a common and early symptom of GBS and requires aggressive treatment. Pain intensity on admission is not a predictor of poor prognosis. Back and leg pain usually resolves over the first 8 weeks, but dysesthetic extremity pain may persist longer in 5 to 10% of patients despite motor recovery and the use of adjuvant analgesics. NEUROLOGY 1997;48: 328-331
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Clinical Autonomic Disorders was compiled as a comprehensive summary of current knowledge about the diagnosis and treatment of autonomic dysfunction, with an emphasis on disorders of peripheral nerves. On the whole, Dr Low has fulfilled that ambition. Although the book clearly reflects the author's own special interests, both as a clinician dealing with autonomic neuropathies and as founder of an autonomic laboratory at the Mayo Clinic, its 800 pages and 56 chapters present a broad view of autonomic function and failure. It is reasonably up-to-date, references in most chapters extending to 1991.The massive text is organized into three major sections: basic science, clinical evaluation, and clinical disorders. This plan inevitably leads to repetition and overlap, but, if the book is used as a source of individual short monographs, this may not be a problem. Careful attention by the editor has ensured good consistency among the authors, so that there
Article
The bladder has only two essential functions. It stores and periodically empties liquid waste. Yet it is unique as a visceral organ, allowing integrated volitional and autonomous control of continence and voiding. Normal function tests the integrity of the nervous system at all levels, extending from the neuroepithelium of the bladder wall to the frontal cortex of the brain. Thus, dysfunction is common with impairment of either the central or peripheral nervous system. This monograph presents an overview of the neural control of the bladder as it is currently understood. A description of pertinent peripheral anatomy and neuroanatomy is provided, followed by an explanation of common neurophysiological tests of the lower urinary tract and associated structures, including both urodynamic and electrodiagnostic approaches. Clinical applications are included to illustrate the impact of nervous system dysfunction on the bladder and to provide indications for testing. © 2008 Wiley Periodicals, Inc. Muscle Nerve 38: 815–836, 2008
Article
Quantification of the complex, autonomic networks in the skin is difficult. Although sporadic attempts focusing mainly on sudomotor plexus have been reported, an easy and reliable method of quantification has not yet been made available. We developed a method to quantify pilomotor nerve fibers (PNFs), which, compared to sudomotor nerves, have a less complex pattern. We used this procedure on a population of normal and diabetic subjects, and propose it as a new tool to study cutaneous autonomic nerves. Skin biopsies were performed from thigh and distal leg in 20 diabetic patients and 20 age- and sex-matched controls. Samples were processed applying indirect immunofluorescence and using pan-neuronal and selective markers for cholinergic and noradrenergic fibers. Pilomotor nerve fiber density was blindly calculated on single 2-μm optical sections selected from confocal z-stacks. Interobserver and intraobserver reliability was evaluated. Results were compared with values obtained by 2 other methods that explored PNFs more extensively. Pilomotor nerve fibers density was compared to epidermal nerve fiber (ENF) density, to pilocarpine-activated sweat gland density, and to the severity of neuropathy as assessed by the modified total neuropathy score. A significant loss of PNFs was found in diabetic subjects' thigh and leg. PNFs density did not correlate with ENF density, disease duration, or total neuropathy score. Noradrenergic PNFs correlated instead with sweating impairment. A reliable assessment of PNF density is possible. When studying cutaneous innervation, PNF quantification should be done to gain information on autonomic nerves in addition to somatic nerves.
Article
Amitriptyline is frequently used to treat patients with interstitial cystitis/painful bladder syndrome. The evidence to support this practice is derived mainly from a small, single site clinical trial and case reports. We conducted a multicenter, randomized, double-blind, placebo controlled clinical trial of amitriptyline in subjects with interstitial cystitis/painful bladder syndrome who were naïve to therapy. Study participants in both treatment arms received a standardized education and behavioral modification program. The drug dose was increased during a 6-week period from 10 up to 75 mg once daily. The primary outcome was a patient reported global response assessment of symptom improvement evaluated after 12 weeks of treatment. A total of 271 subjects were randomized and 231 (85%) provided a global response assessment at 12 weeks of followup. Study participants were primarily women (83%) and white (74%), with a median age of 38 years. In an intent to treat analysis (271) the rate of response of subjects reporting moderate or marked improvement from baseline in the amitriptyline and placebo groups was 55% and 45%, respectively (p = 0.12). Of the subgroup of subjects (207) who achieved a drug dose of at least 50 mg, a significantly higher response rate was observed in the amitriptyline group (66%) compared to placebo (47%) (p = 0.01). When all randomized subjects were considered, amitriptyline plus an education and behavioral modification program did not significantly improve symptoms in treatment naïve patients with interstitial cystitis/painful bladder syndrome. However, amitriptyline may be beneficial in persons who can achieve a daily dose of 50 mg or greater, although this subgroup comparison was not specified in advance.
Article
Aim: The urothelium, or epithelial lining of the lower urinary tract (LUT), is likely to play an important role in bladder function by actively communicating with bladder nerves, smooth muscle, and cells of the immune and inflammatory systems. Recent evidence supports the importance of non-neuronal cells that may extend to both the peripheral and central processes of the neurons that transmit normal and nociceptive signals from the urinary bladder. Using cats diagnosed with a naturally occurring syndrome termed feline interstitial cystitis (FIC), we investigated whether changes in physiologic parameters occur within 3 cell types associated with sensory transduction in the urinary bladder: 1) the urothelium, 2) identified bladder dorsal root ganglion (DRG) neurons and 3) grey matter astrocytes in the lumbosacral (S1) spinal cord. As estrogen fluctuations may modulate the severity of many chronic pelvic pain syndromes, we also examined whether 17beta-estradiol (E2) alters cell signaling in rat urothelial cells. Results: We have identified an increase in nerve growth factor (NGF) and substance P (SP) in urothelium from FIC cats over that seen in urothelium from unaffected (control) bladders. The elevated NGF expression by FIC urothelium is a possible cause for the increased cell body size of DRG neurons from cats with FIC, reported in this study. At the level of the spinal cord, astrocytic GFAP immuno-intensity was significantly elevated and there was evidence for co-expression of the primitive intermediate filament, nestin (both indicative of a reactive state) in regions of the FIC S1 cord (superficial and deep dorsal horn, central canal and laminae V-VIl) that receive input from pelvic afferents. Finally, we find that E2 triggers an estrus-modifiable activation of p38 MAPK in rat urothelial cells. There were cyclic variations with E2-mediated elevation of p38 MAPK at both diestrus and estrus, and inhibition of p38 MAPK in proestrous urothelial cells. Conclusion: Though urothelial cells are often viewed as bystanders in the processing of visceral sensation, these and other findings support the view that these cells function as primary transducers of some physical and chemical stimuli. In addition, the pronounced activation of spinal cord astrocytes in an animal model for bladder pain syndrome (BPS) may play an important role in the pain syndrome and open up new potential approaches for drug intervention.
Article
To evaluate in a prospective study the impact of the "three-drug therapy" (antimuscarinic, alpha-blocker and tricyclic antidepressants) on the treatment of refractory detrusor overactivity (DO). Data from 27 consented patients with refractory DO were available for study. They were asked to complete a daily urinary chart and underwent urodynamic evaluation (UD) before and 60 days after treatment. Response to treatment was considered the presence of one or less involuntary detrusor contractions (IDC) on post-treatment UD. Statistical analysis was performed with Fisher and Mann-Whitney tests, besides Spearman's correlation. P values <0.05 were considered significant. The mean follow-up was 15 months. The comparison of the daily urinary chart before and after treatment showed significant increase on bladder capacity and decreases on urgency, urge-incontinence and frequency. Objective data from UD showed that the mean maximum bladder capacity (MBC) ranged from 200 to 300 mL (P < 0.001) with treatment. The same trend was observed with the other UD variables. When compared to baseline, the questionnaire OAB-v8 showed significant improvement (P < 0.01). Main side effects comprised dry mouth and constipation (40%), with average scores of 5.16 and 3.08, respectively (visual scale from 0 to 10). Triple therapy may be an effective, easily employed and well-tolerated option to refractory DO treatment. More studies are necessary to achieve more consistent data on the matter.
Article
Study lower urinary dysfunction in familial amyloidotic polyneuropathy (FAP). Fifty-four FAP patients were studied. Clinical examination, urodynamics and ultrasound of the urinary tract were performed. Urinary symptoms appeared during the first three years of the disease in 50% of the patients. The initial urinary symptom was dysuria in 39% and incontinence in 24% of the patients, sensitivity and contractility disturbances of the detrusor were found at the initial stages. Non-relaxing urethral sphincter was found in 51,7% and dyssynergia in 37,5% of the cases. Ultrasound revealed thickening of the vesical wall in 42,5% of the patients, more common in males (M:16; F:7). Opening of the vesical neck was found in 56% of the cases (M:19; F:11) with paradoxical closure during the attempt to void. Fluctuations in the opening of the vesical neck were found in eight patients, also more frequently in males (M:6; F:2). In addition to reduced sensation, underactive detrusor, opening of the vesical neck and external sphincter deficit, we found data suggesting failure of relaxation of the internal and external sphincter. The overdistention associated with an open vesical neck and external sphincter deficit justifies incontinence in those patients. The retention is due to inadequate contraction of the detrusor, probably associated with non-relaxing of the internal and external sphincter. These dysfunctions derive from deposition of amyloid substance in the detrusor, but overdistention is likely to play a role. Early therapeutic intervention in these patients is vital to avoid secondary injuries.
Article
We studied a four-generation pedigree of a Japanese family with hereditary neuropathy to elucidate the genetic basis of this disease. Twelve members of the family were enrolled in this study. The clinical features were neurogenic muscle weakness with proximal dominancy in the lower extremities, sensory involvement, areflexia, fine postural tremors, painful muscle cramps, elevated creatine kinase levels, recurrent paroxysmal dry cough, and neurogenic bladder. We performed a genome-wide search using genetic loci spaced at about 13 Mb intervals. Although nine chromosomes (1, 3, 4, 5, 6, 10, 17, 19, and 22) had at least one region in which the logarithm of odds (LOD) score was over 1.0, no loci fulfilled the criteria for significant evidence of linkage. Moreover, we analyzed an extra 14 markers on 3p12-q13 (the locus of hereditary motor and sensory neuropathy, proximal dominant form) and an extra five markers on 3p22-p24 (the locus of hereditary sensory neuropathy with chronic cough) and observed LOD scores of <-3 on both 3p12-q13 and 3p22-p24. Mutation scanning of the entire coding regions of the MPZ and PMP22 genes revealed no mutations. We conclude that the disorder described here is a newly classified hereditary motor and sensory neuropathy with autosomal dominant inheritance.
Article
Established urodynamic and electrophysiological techniques have been applied to assess the frequency and extent of autonomic and peripheral neuropathy in 60 subjects with diabetes mellitus; 38 were diabetics with suggestive symptoms and the others were representative newly diagnosed (11) or treated (11) diabetics. Objective evidence neuropathic bladder dysfunction was detected in 43 of them (71.7%). The commonest abnormality was a hypotonic, insensitive large capacity bladder, which condition was usually asymptomatic. Less freuqently (15%) was this complicated by bladder decompensation and sphincter involvement, resulting in excessive residual urine and infection; some of these had bladder paralysis with chronic painless retention of urine (7%). Electrophysiological studies found a sensory defect in the lower limbs in all tested patients (100%), and in 41 patients (69%) as associated motor conduction abnormality, which was more frequent and marked in the lower than the upper limb. These functional abnormalities appeared to be related to the severity of diabetes, but less to its duration. Indeed of 11 newly diagnosed diabetics tested 7 had a peripheral neuropathy and 4 urodynamic abnormalities. The high incidence of bladder dysfunction and peripheral neuropathy in this series indicates the frequency of subclinical diabetic neuropathy and a factor needing more emphasis in diabetic uropathy.
Article
An electrophysiological method has been developed to test the structural integrity and function of the reflex arcs concerned with micturition. The technique has been used to delineate neuropathic involvement of the lower urinary tract.
Article
Clinical, electrophysiological and pathological findings in 23 patients with subacute and relapsing idiopathic demyelinating polyneuropathies are described. In 17 patients with relapsing polyneuropathy, the neurological illness was unaccompanied by any systemic disturbances. The term preferred for the neuropathy in this group of patients is chronic relapsing polyneuritis. The findings in this group suggest that the common form of this syndrome is due to a single disease entity. Chronic relapsing polyneuritis differs from acute idiopathic polyneuritis chiefly in regard to the rate of evolution and the severity of the initial episode of polyneuropathy. If these two polyneuropathies have the same pathogenesis, the factor which determines whether the disease is acute and self-limiting or chronically relapsing is often present at the time of onset of the disease. The relationship of chronic relapsing polyneuritis to relapsing hypertrophic polyneuropathy and progressive hypertrophic polyneuropathy is also discussed and it is concluded that these diseases may constitute a spectrum of pathogenetically related disorders. In chronic relapsing polyneuritis, as in other demyelinating polyneuropathies, a marked segmental reduction in axon diameter accompanies demyelination. This corresponds to a more than 50% reduction in the volume of the affected region of the axon and it is associated with increased packing of axoplasmic organelles and wrinkling of the axolemma. It is suggested that in the normal myelinated nerve fibre, the Schwann cell and myelin sheath maintain fluid locally within the axon.
Article
This is the first report of incidence of neurogenic bladder in patients with acquired immune deficiency syndrome (AIDS) and emphasizes that it is a significant cause of various voiding dysfunctions in these patients. Neurologic disease occurs in about one third of patients with AIDS. Both central and peripheral nervous systems may be involved. Urodynamic evaluation is necessary for assessment and management of neurogenic voiding disorders in this group of patients.
Article
Clinical data are presented of 63 artificially ventilated Guillain-Barré patients. About half of them had an antecedent event. In 57% the disease was heralded by sensory symptoms. The mean progressive phase lasted 12 days, the plateau 12 days and the recovery phase 568 days. In all patients one or more cranial nerves were involved, most often leading to facial palsy or difficulties in swallowing. Three-quarters of the patients had sensory signs, proprioceptive more often than superficial. Autonomic disturbances were common, especially hypertension and tachycardia. Twenty-two percent of the patients were severely confused in the first weeks of the disease. Laboratory examination showed atypical lymphocytes in the blood of 37% of patients and disturbed hepatic function tests in 79%. CSF protein level was elevated in all patients, with a mean value of 1.5 g/l.
Article
Experience in the detection of absent vesicoureteral reflux with bethanechol-aided voiding cystourethrography is presented. The detection rate with conventional contrast-enhanced voiding cystourethrography among 9 study subjects, in whom vesicoureteral reflux otherwise was highly suspected from accompanying clinical, urographic and endoscopic features, and in whom it was absent contralaterally or bilaterally, was improved from 33 per cent (only 3 of 9 patients were positive for reflux) to 100 per cent (all 9 were proved to have vesicoureteral reflux) after bethanechol stimulation. Some representative cases are presented and the mechanisms of inducing vesicoureteral reflux with bethanechol are discussed as well as its clinical relevance. Bethanechol-aided voiding cystourethrography is suggested as a highly sensitive method to detect absent vesicoureteral reflux.
Article
In this review of the acquired immunodeficiency syndrome (AIDS), the authors have evaluated a total of 352 homosexual patients with AIDS or generalized lymphadenopathy managed at the University of California, San Francisco (UCSF), between 1979 and 1984. Of an initial unselected group of 318 patients, 124 (39%) were neurologically symptomatic, and one-third already had their neurological complaints at the time of presentation. An additional 210 AIDS patients with neurological symptoms have been reported in the literature. Thus, a total of 366 neurologically symptomatic patients with AIDS or lymphadenopathy are reviewed. Central nervous system (CNS) complications, encountered in 315 patients, included the following viral syndromes: subacute encephalitis (54), atypical aseptic meningitis (21), herpes simplex encephalitis (nine), progressive multifocal leukoencephalopathy (six), viral myelitis (three), and varicella-zoster encephalitis (one). Non-viral infections were caused by Toxoplasma gondii (103), Cryptococcus neoformans (41), Candida albicans (six), Mycobacteria (six), Treponema pallidum (two), coccidioidomycosis (one), Mycobacterium tuberculosis (one), Aspergillus fumigatus (one), and Escherichia coli (one). Neoplasms included primary CNS lymphoma (15), systemic lymphoma with CNS involvement (12), and metastatic Kaposi's sarcoma (three). Cerebrovascular complications were seen in four patients with hemorrhage and five with infarction. Five patients in the UCSF series had multiple intracranial pathologies, including two cases of simultaneous Toxoplasma gondii infections and primary CNS lymphoma, two cases of coexistent Toxoplasma gondii and viral infections, and one case of combined Toxoplasma gondii and atypical mycobacterial infection. Cranial or peripheral nerve complications, seen in 51 patients, included cranial nerve syndromes secondary to chronic inflammatory polyneuropathy (five), lymphoma (five), and Bell's palsy (five). Peripheral nerve syndromes included chronic inflammatory polyneuropathy (12), distal symmetrical neuropathy (13), herpes zoster radiculitis (six), persistent myalgias (two), myopathy (two), and polymyositis (one). In light of the protean behavior of AIDS and the problems related to the clinical, radiological, and serological diagnosis of the unusual and varied associated nervous system diseases, patients with AIDS and neurological complaints require a rigorous and detailed evaluation. The authors' experience suggests that biopsy of all CNS space-occupying lesions should be performed for tissue diagnosis prior to the institution of other therapies.
Article
A survey of the literature of neurological manifestations associated with the acquired immune deficiency syndrome (AIDS) shows a broad disease spectrum affecting approximately one third of the patients in large hospital series. The complications include focal cerebral lesions caused by abscesses, lymphomas, leucoencephalopathy or infarcts as well as encephalitis, meningitis and myelitis. Most opportunistic infections of the central nervous system presumably are caused by toxoplasma gondii, cytomegalovirus and cryptococcus neoformans. One tenth of all patients have neurological disease as their initial symptom of AIDS. The diagnosis should always be considered in patients at risk and in males with an unusual neurological history or with a peculiar CT scan of the brain. Besides the opportunistic complications of AIDS, LAV/HTLV-III itself probably attacks the nervous system and gives rise to concomitant lesions of the long tracts of the spinal cord with ataxia, paresis and spasticity and to subacute encephalopathy and peripheral nerve abnormalities as well.
Article
Neurological manifestations are common in HIV-infected individuals. Autopsy data suggest that the brain may be affected in as many as 80 per cent of cases. While opportunistic infections represent a major cause of neurological morbidity and mortality, there is growing evidence that HIV is itself neurotropic and can directly affect the nervous system.
Article
The incidence of autonomic dysfunction as a complication of diabetes mellitus is reported to be as high as 20% to 40%. Symptoms of diabetic autonomic neuropathy (DAN) are often vague, and signs difficult to detect on routine physical examination. The early diagnosis of DAN is possible by utilizing several simple noninvasive tests, which may also be helpful in localizing the lesion(s) to specific autonomic pathways. DAN may affect multiple organ systems, to include cardiovascular, gastrointestinal, genitourinary and/or neuroendocrine, and may, in fact, be life-threatening. The same metabolic disturbances of somatic peripheral nerve may also be responsible for DAN. Like somatosensory neuropathy, definitive therapy for DAN is not yet satisfactory, although multiple chemotherapeutic agents have been tried and warrant further investigation.
Article
The following tests of autonomic function were performed on seven patients with the Guillain-Barré syndrome and compared with controls: (1) measurement of heart rate and blood pressure in the supine and erect positions, (2) measurement of baroreflex sensitivity, (3) Valsalva's manoeuvre, (4) sweat test. In two patients the heart rates were fixed and greater than 100/min and in three there was postural hypotension. The baroflex sensitivity of four patients was abnormal and heart rate response to Valsalva's manoeuvre was impaired in two of the three patients who were able to perform the manoeuvre. Areas of anhidrosis were found in all seven patients. These abnormalities probably reflect pathological alterations of the sympathetic and parasympathetic components of the autonomic nervous system of patients with Guillain-Barré syndrome. The severity of autonomic involvement is not related to the degree of sensory and motor disturbance which is consistent with the patchy distribution of lesions throughout the peripheral and autonomic nervous systems.
Article
Fifty patients with acquired immune deficiency syndrome had complications affecting the central or peripheral nervous systems or both. The patients were either male homosexuals, intravenous drug abusers, or recently arrived Haitian refugees. They ranged in age from 25 to 56. Central nervous system complications were of four kinds: (1) Infections included Toxoplasma gondii abscesses in 5 patients, progressive multifocal leukoencephalopathy in 2, cryptococcal meningitis in 2, Candida albicans in 1, and possible Mycobacterium avium intracellulare in 3. Eighteen patients suffered a subacute encephalitis possibly attributable to cytomegalovirus infection. (2) Tumors consisted of primary lymphoma of the brain in 3 patients and meningeal invasion by systemic lymphoma in 4. (3) Vascular complications included nonbacterial thrombotic endocarditis in 2 patients and cerebral hemorrhages in the setting of thrombocytopenia in 3. (4) Undiagnosed central nervous system problems were evidenced as focal brain lesions in 3 patients and self-limiting aseptic meningitis in 4. Peripheral neuropathy occurred in 8 patients.
Article
A linkage study was performed on three families with classic Charcot-Marie-Tooth (CMT) hereditary neuropathy with clinical manifestations of autosomal dominant inheritance, distal muscle weakness and atrophy, hyporeflexia, and slow motor nerve conduction velocities. Two families comprising 3 and 4 generations and a total of 23 affected persons were informative for the Duffy locus known to be on the long arm of chromosome 1. The maximum total lod score was 2.297 at recombination fraction theta = .1. The third family was informative for PGM1 (on the short arm of chromosome 1). There was no evidence for linkage of CMT to PGM1 in this third family, but only values of theta less than .03 could be excluded. There was no evidence for linkage of CMT to seven other informative markers in these families. We conclude that the gene controlling the occurrence of dominant CMT may be approximately 10 centimorgans from the Duffy locus on the long arm of chromosome 1. Additional studies are required to confirm these findings.
Article
Detailed urodynamic and neurologic evaluation of 550 patients was reviewed with the intention of shedding light on the understanding of the neurophysiologic pathways involved in micturition. On the basis of our data the following conclusions were made: 1) normal micturition is a brain stem reflex rather than a simple sacral reflex, 2) interruption of this sacral-to-brain stem reflex pathway results in uncoordinated voiding (detrusor-external sphincter dyssynergia), 3) anatomically separate neural centers control the activity of the detrusor muscle and the external urethral sphincter, and 4) although the pudendal and pelvic nuclei are located in the sacral spinal cord they are anatomically separable from one another.
Article
During the past decade the ability to assess urinary bladder function in diabetes mellitus has improved considerably because of changed concepts of urinary bladder function, imporved methods for evaluation, and increased capability for treatment. Evaluation of patients with urinary bladder dysfunction and diabetes mellitus has shown that peripheral visceral afferent pathways are first affected, followed by detrusor reflex decompensation.
Article
The diabetic neurogenic paralytic bladder is characterized by marked residual urine, secondary infection, pyelonephritis, sepsis, and azotemia. Initial manifestations were studied in diabetic patients with and without neuropathy and in nondiabetic controls, all without symptoms referable to the urinary tract. The nondiabetic controls and the diabetics without neuropathy were urologically normal. Eighty-three percent of the diabetic patients with neuropathy had objective evidence of neurogenic bladder involvement; however, there was no residual urine, infection, pyelonephritis, sepsis or azotemia. The disparity between early and late bladder involvement is determined by the factor of residual urine, which is the measure of advancing bladder neuropathy leading to decompensation. Progressive decompensation of the asymptomatic diabetic bladder may be a cause of the increased frequency of renal infection in diabetic patients.
Article
The precise incidence and prevalence of diabetic cystopathy are difficult to determine because of the insidious onset, discrete symptoms, and differences in the definition of bladder dysfunction. Diabetic cystopathy, classified according to urophysiological criteria, was shown to occur in 43% to 87% of insulin-dependent diabetics, with no sex or age differences. Another study showed an average 25% prevalence of diabetic cystopathy in patients on oral hypoglycemic treatment. A Scandinavian study showed that in patients who have had diabetes for 10 years, the prevalence of diabetic cystopathy in those who were insulin-dependent was two to four per 1000 and in those on oral hypoglycemic agents was one to three per 1000. The correlation between diabetic cystopathy and peripheral neuropathy ranged from 75% to 100%. Nephropathy was seen in 30% to 40% of cases. The higher frequency of urinary tract infections in diabetics is not related to diabetic cystopathy but to the frequent occurrence of non-neurogenic bladder outlet disorders, especially in older women.
Article
Disturbances of urinary bladder function are well-recognized problems in diabetic patients and are generally attributed to peripheral neuropathy. Because of the difficulties inherent in the histologic examination of the peripheral autonomic nerves, little is known about the pathology of these nerves. Recently, alterations have been observed in fine axons in the bladder wall in diabetic subjects. Pathologic changes have also been observed in ganglia of the bladder wall. Abnormalities previously described in the autonomic ganglia and nerve trunks of diabetic subjects may also be important in the development of urinary bladder dysfunction.
Article
Voiding dysfunction in diabetics has been attributed to a variety of causes including an axonopathy in autonomic pathways to the urinary bladder. The present study was undertaken to determine whether changes occurred in afferent and efferent neurons supplying bladders of streptozotocin (STZ)-induced diabetic rats. Nine weeks after STZ treatment, the mean cross-sectional area for retrogradely labeled (Fluoro-Gold) bladder neurons in the major pelvic ganglion (MPG) was greater in diabetics (364 microns 2) than controls (300 microns 2). The number of labeled neurons was similar in these groups. In contrast, mean cross-sectional areas of bladder afferent neurons labeled with WGA-HRP in the L6 and S1 dorsal root ganglia (DRG) were smaller (393 microns 2) in diabetics than in normal rats (528 microns 2). In addition, very few DRG neurons were labeled in STZ-treated rats and transganglionic labeling of bladder afferent projections in the L6 and S1 spinal cord with WGA-HRP was sparse. Radioimmunoassay studies revealed that substance P was reduced by 70% in the MPG and by 40% in L6 DRG, yet this peptide was unchanged in the bladders of diabetic rats. The amounts of VIP in the MPG and DRG of diabetics and controls were similar, while VIP in the bladder was increased in diabetics. These observations indicate that both afferent and efferent neurons innervating the urinary bladder are altered in the STZ-induced diabetic rat. In addition, axonal transport in visceral afferent pathways may be disrupted.
Article
To ascertain the relationship between voiding dysfunction associated with diabetes and bladder and sphincter behavior, the video urodynamic studies of 182 patients were retrospectively analyzed. Patients were classified based on urodynamic diagnosis and the presence or absence of signs of sacral cord involvement. Urodynamic findings were classified as either detrusor hyperreflexia, impaired detrusor contractility, detrusor areflexia, indeterminate and normal. The results indicate that mean bladder capacity was 485 +/- 89.3 ml. with a mean first sensation of filling of 298 +/- 67.4 ml. Of the 182 patients 100 (55%) had detrusor hyperreflexia, 42 (23%) had impaired detrusor contractility, 20 (11%) had indeterminate findings, 19 (10%) had detrusor areflexia and 1 (1%) was normal. Bladder outlet obstruction occurred in 66 patients (36%), all men (57%). The diagnosis was isolated in 24 patients (36%) or in combination with another diagnosis in 42 (74%). However, if one considers the presence of sacral cord signs (42 patients), the most common urodynamic diagnoses were either impaired detrusor contractility in 21 (50%) or detrusor areflexia in 10 (24%). These data suggest that classical diabetic cystopathy is not the most common urodynamic findings in patients with diabetes mellitus and voiding dysfunction, and in fact these patients present with variable pathophysiological findings. These findings demonstrate the importance of urodynamic studies in diagnosing voiding dysfunction in diabetics before initiation of therapy.
Article
Human immunodeficiency virus (HIV) infections often lead to urological disorders, including tumors, infections and micturitional disturbances. It often is difficult to identify the origin of voiding disorders but the most frequent causes are infections (prostatitis and so forth), obstruction (cervico-prostatic or urethral) and neurological (encephalitis, myelitis, polyradiculoneuritis and so forth). We determined the etiologies, therapy and clinical outcome of micturitional disturbances in the acquired immunodeficiency syndrome. Between February 1989 and September 1992 we studied prospectively 39 HIV positive patients with voiding symptoms, such as straining, urinary retention, frequency and urgency. Each patient underwent a thorough neurological and urological examination, along with radiological evaluation of the urogenital tract and nervous system. Urodynamic evaluation was performed to specify the etiology and type of disturbance before treatment. The patients were followed for 2 to 24 months (mean 9) and 34 (87%) had urodynamic abnormalities, including a hyperactive bladder, bladder sphincter dyssynergia and a hypoactive bladder. The cause of the voiding disorder was neurological in 61.5% of the cases, and the 2 most frequent disorders were cerebral toxoplasmosis and HIV encephalitis. Treatment was usually given to relieve symptoms with drugs acting on the detrusor-sphincter complex. A total of 22 patients (57%) had lasting improvement, while 17 (43%) died 2 to 24 months (mean 8) after onset of the voiding symptoms. A micturition problem is an unfavorable event since it usually indicates a neurological cause.
Article
Autonomic dysfunction is a common complication of peripheral neuropathies. It is often of little clinical importance, but some conditions may cause profound disturbance of autonomic function. These conditions include acute dysautonomia, diabetes, primary and familial amyloidosis, Guillain-Barré syndrome, porphyria, and some inherited neuropathies. A wide range of neuropathies are associated with lesser degrees of autonomic dysfunction. These include hereditary neuropathies, and neuropathies associated with metabolic disturbances, alcohol abuse, malignancy, medications, infections, and connective tissue disorders.
Article
The possible relationship between bladder dysfunction and autonomic neuropathy was investigated in unselected diabetic patients. Bladder function was examined by cystometry in 53 unselected diabetic patients and 10 healthy controls. Sympathetic skin response was recorded in 23 of 53 patients and all control subjects to evaluate autonomic neuropathy associated with diabetes, and the results were compared to cystometric findings. Cystometrograms exhibited significant increases in bladder volume at first desire to void and maximal bladder capacity, and a decrease in detrusor contractility in diabetic patients compared to those in controls. In addition, mean residual urine was significantly larger in diabetic patients than in controls. Among the 53 diabetic patients these bladder dysfunctions were also found in each subset of patients with no sign of retinopathy (33), no subjective urinary symptoms (32) or duration of diabetes less than 1 year (12). In 23 patients in whom sympathetic skin response was measured 12 without sympathetic skin responses had increased residual urine and decreased detrusor contraction pressure. The remaining 11 patients with a lower amplitude of sympathetic skin response and more prolonged latency than controls had a significant decrease in detrusor contraction pressure. Bladder dysfunction, characterized by loss of sensation, increased capacity and decreased contractility, was the main observation of diabetic cystopathy regardless of the duration or severity of the disease. The association of bladder dysfunction and autonomic neuropathy detected by the sympathetic skin response might indicate that diabetic cystopathy is a manifestation of peripheral neuropathy induced by diabetes.
Article
To examine the frequency and pathophysiology of micturitional disturbance in patients with Guillain-Barré syndrome. Micturitional symptoms were noted and neurological examinations made repeatedly during admission to hospital of patients with clinical and neurophysiologically definite Guillain-Barré syndrome. Urodynamic studies consisted of uroflowmetry, measurement of residual urine, urethral pressure profilometry, medium fill water cystometry, and external sphincter EMG. Seven of 28 (25%) patients with Guillain-Barré syndrome showed micturitional disturbance. The symptoms included voiding difficulty in six, urinary retention in three, nocturnal urinary frequency in three, and urge incontinence in two. These micturitional symptoms appeared after weakness occurred, and improved gradually along with the neurological signs. All three patients who showed retention became able to urinate. Urodynamic studies were made on four symptomatic patients two of whom underwent repeated study. Disturbed bladder sensation was noted in one patient, bladder areflexia in one, and absence of the bulbocavernosus reflex in one. Cystometry showed decreased bladder volume in two and bladder overactivity in two, one of whom had urge urinary incontinence and the other urinary retention. A quarter of the patients with Guillain-Barré syndrome tend to have micturitional disturbance. The patients studied had evacuation and storage disorders, as well as bladder areflexia and disturbed bladder sensation indicative of peripheral types of parasympathetic and somatic nerve dysfunction. Decreased bladder volume with bladder overactivity but no evidence of CNS involvement was also found, evidence that bladder overactivity also occurs in peripheral nerve lesions with probable pelvic nerve irritation.
Article
Guillain-Barré syndrome (GBS) is viewed as a reactive, self-limited, autoimmune disease triggered by a preceding bacterial or viral infection. Campylobacter jejuni, a major cause of bacterial gastroenteritis worldwide, is the most frequent antecedent pathogen. It is likely that immune responses directed towards the infecting organisms are involved in the pathogenesis of GBS by cross-reaction with neural tissues. The infecting organism induces humoral and cellular immune responses that, because of the sharing of homologous epitopes (molecular mimicry), cross-react with ganglioside surface components of peripheral nerves. Immune reactions against target epitopes in Schwann-cell surface membrane or myelin result in acute inflammatory demyelinating neuropathy (85% of cases); reactions against epitopes contained in the axonal membrane cause the acute axonal forms of GBS (15% of cases). Care for such patients may be challenging, yet the prognosis overall is favourable. Optimal supportive care and anticipation and prevention of complications are the mainstay of therapy. Admission to the intensive-care unit is necessary in 33% of patients who require intubation and assisted ventilation. Immunomodulation with infusions of IgG or plasma exchange treatments foreshorten the disease course.