Multiple system atrophy is a disorder characterized by progressive neuronal atrophy at certain sites of the central nervous system, several of which are important in the control of urogenital function. The neuro-urological features of 62 patients with this condition are described. All patients had abnormal urethral or anal sphincter electromyography when individual motor unit analysis was performed, a finding diagnostic of the condition in the appropriate clinical setting. Impotence occurred in 96% of the men and was the first symptom alone in 37%. Urinary symptoms resulted from a combination of detrusor hyperreflexia and urethral sphincter weakness followed by failure of detrusor contraction. In men these symptoms simulated those of outflow obstruction so that 43% underwent prostatic or bladder neck surgery before the correct diagnosis was made. Stress incontinence occurred in 57% of the women and of these half had undergone surgery. The results of surgery in both sexes were poor. Treatment with intermittent catheterization, anticholinergic medication and desmopressin spray markedly improved continence in 82%. The importance of recognizing this disorder and introducing effective, nonoperative treatments is stressed.

An intravesical instillation of 100 ml 1 or 2 mmolIl capsaicin has been used to treat detrusor hyperreflexia giving rise to intractable urinary incontinence in 12 patients with spinal cord disease and two other patients with detrusor overactivity of non-spinal origin. Nine patients, all of whom had spinal cord disease, showed some improvement in bladder function. The benefit was only shortlived and partial in four, but the remaining five achieved complete continence while performing intermittent self catheterisation. Urodynamic studies in these nine patients showed an increase in mean (SD) bladder capacity from 106 (57) to 302 (212) ml and a fall in the maximum detrusor pressure from 54 (20) Detrusor hyperreflexia can result either from loss of the normal inhibitory input from higher centres on to the pontine micturition centre or after a spinal lesion from interruption of the spinobulbospinal pathways that normally control physiological bladder behaviour. Animal models of chronic spinal cord disease have shown that after disruption of the connections between the pons and the sacral spinal cord a new segmental sacral reflex arc becomes functional.' The afferent neurones of this emergent reflex in the cat are mostly unmyelinated C fibres whereas in the neurologically intact animal afferent neurones from the bladder are small myelinated A5 fibres.2 Little is known of the neurological mechanism of bladder reflexes in spinally injured humans.' Disconnection of the sacral cord from the pons results in detrusor areflexia that lasts for about six weeks before volume determined bladder reflex emptying becomes established. A speculative hypothesis is that this change in detrusor behaviour results from synaptic reorganisation and possibly new nerve growth forming the neurological basis of an emerging reflex arc.Pharmacological experiments show that in many species there is a large group of fibres innervating the bladder that are capsaicin sensitive.3-6 These are mostly unmyelinated fibres in the cat' and rat.7 They are silent under physiological conditions but may be activated by bacterial or chemical irritants in the bladdere giving rise to symptoms of cystitis. It is probably these same fibres that emerge active and serve as the afferent arc for detrusor hyperreflexia in spinally injured animals. ' Capsaicin activates a vanilloid receptor on the cell membrane of sensitive primary sensory neurones9 causing an increase in cation permeability and leading to membrane depolarisation. Activation of the vanilloid receptor produces a biphasic response. The immediate effect is stimulatory with transmission of sensory impulses from the periphery to the central nervous system sensed as a painful irritation and a peripheral release from the receptor terminals of neuropeptides including substance P and CGRP. After exposure to high concentrations of capsaicin, afferent C fibres may show long lasting functional

Although autonomic failure, parkinsonism, and cerebellar and pyramidal signs are well documented in multiple system atrophy, much less is known about the frequency and severity of involvement of the peripheral nervous system. The frequency and nature of peripheral nerve involvement has therefore been determined in 74 patients with multiple system atrophy using nerve conduction studies and skeletal muscle EMG. These findings were compared with those on sphincter EMG. Ninety per cent of the patients had an abnormal sphincter EMG, indicating denervation and reinnervation consistent with anterior horn cell loss in Onuf's nucleus, but only 40% PATIENTSSeventy four patients with clinically probable multiple system atrophy (pathologically established in 11) underwent peripheral electrophysiological studies (n = 40) or sphincter EMG (n = 71), or both. All patients undergoing peripheral electrophysiological studies had both nerve conduction studies and skeletal muscle EMG. In 35 patients both peripheral electrophysiological studies and sphincter EMG were performed. Fifty one of the patients were men (68%) and 23 were women (32%). Their mean age at the time of sphincter electromyography was 52-8 (range 33-67) years, and at the time of peripheral electrophysiological studies (nerve conduction studies and skeletal muscle EMG) it was 55-1 (41-67) years.Patients were diagnosed according to published clinical criteria.'0 There were 56 (76%) patients with multiple system atrophy of striatonigral degeneration (SND) type, either with (24) or without (32) cerebellar signs. Eighteen (24%) patients were classified as having multiple system atrophy of olivopontocerebellar atrophy (OPCA) type, either without ("pure" OPCA type, eight) or with ("predominant" OPCA type, 10) extrapyramidal features.The mean age at onset of the first symptoms was 50 3 (range 33-71) years.Symptoms at onset were autonomic dysfunction in 28 (38%), parkinsonism in 25 (34%), cerebellar dysfunction in seven (9%), and mixed in the remaining 18% of these patients. The most common initial diagnosis was Parkinson's disease, then cerebellar syndrome, and then multiple system atrophy. At

Early diagnosis of multiple-system atrophy (MSA) is important in patients presenting with late-onset cerebellar ataxia because it has a less favourable prognosis than other degenerative ataxic disorders. We report cerebellar presentation of MSA in a series of 16 patients, 3 of whom later developed parkinsonism. Two-thirds of them had early evidence of impaired postural reflexes with a history of recurrent falls. Some of these had a narrow-based, unsteady gait, unlike the more classic broad-based gait ataxia of cerebellar disease. On review of the patients' histories, genitourinary dysfunction (particularly impotence) was present at the onset of, or preceding, cerebellar ataxia in 60% of patients, but this had often been attributed to age, or to urological or gynaecological causes. External striated anal or urethral sphincter electromyography (EMG) demonstrated features of chronic denervation and reinnervation in 14 (93%) of 15 patients, consistent with degeneration in Onuf's nucleus as occurs in MSA. Autonomic function tests were abnormal in 9 (64%) of 14 patients. Our data suggest that close enquiry into genitourinary function and analysis of the gait disorder can be useful pointers to a diagnosis of MSA in patients with an unexplained adult-onset progressive cerebellar syndrome, and that sphincter EMG is the most useful investigation in this context.

Summary Background Transurethral resection of the prostate (TURP) is the standard operation for benign prostatic obstruction. Thulium laser transurethral vaporesection of the prostate (ThuVARP) is a technique with suggested advantages over TURP, including reduced complications and hospital stay. We aimed to investigate TURP versus ThuVARP in men with lower urinary tract symptoms or urinary retention secondary to benign prostatic obstruction. Methods In this randomised, blinded, parallel-group, pragmatic equivalence trial, men in seven UK hospitals with bothersome lower urinary tract symptoms or urinary retention secondary to benign prostatic obstruction were randomly assigned (1:1) at the point of surgery to receive ThuVARP or TURP. Patients were masked until follow-up completion. Centres used their usual TURP procedure (monopolar or bipolar). All trial surgeons underwent training on the ThuVARP technique. Co-primary outcomes were maximum urinary flow rate (Qmax) and International Prostate Symptom Score (IPSS) at 12-months post-surgery. Equivalence was defined as a difference of 2·5 points or less for IPSS and 4 mL per s or less for Qmax. Analysis was done according to the intention-to-treat principle. The trial is registered with the ISRCTN Registry, ISRCTN00788389. Findings Between July 23, 2014, and Dec 30, 2016, 410 men were randomly assigned to ThuVARP or TURP, 205 per study group. TURP was superior for Qmax (mean 23·2 mL per s for TURP and 20·2 mL per s for ThuVARP; adjusted difference in means −3·12, 95% CI −5·79 to −0·45). Equivalence was shown for IPSS (mean 6·3 for TURP and 6·4 for ThuVARP; adjusted difference in means 0·28, −0·92 to 1·49). Mean hospital stay was 48 h in both study groups. 91 (45%) of 204 patients in the TURP group and 96 (47%) of 203 patients in the ThuVARP group had at least one complication. Interpretation TURP and ThuVARP were equivalent for urinary symptom improvement (IPSS) 12-months post-surgery, and TURP was superior for Qmax. Anticipated laser benefits for ThuVARP of reduced hospital stay and complications were not observed. Funding UK National Institute for Health Research Health Technology Assessment Programme.