Properties of the descending limb of the spinobulbospinal micturition reflex pathway in the cat

The micturition reflex is thought to be mediated by a spinobulbospinal reflex pathway passing through the rostral pons. This study examined the properties of the descending limb of the reflex pathway by monitoring the responses of the lower urinary tract to stimulation of the pons in the decerebrate cat. Electrical stimulation (300 μs pulses at 50 Hz intratrain frequencies, 300–500 ms trains, 0.5–15 V) in the region of the locus coeruleus (P 0.5–3.1/L 2–4/H to −2.75) was used to activate the descending excitatory pathway to the sacral parasympathetic nucleus. Low intensity stimulation induced small amplitude, short duration (14 ± 11cm H₂O, 10 ± 3s) bladder contractions in a partially full bladder, whereas higher intensity stimulation induced large amplitude, long duration (69 ± 29cm H₂O, 70 ± 44s) contractions which were similar to distension-induced reflex micturition contractions. The evoked bladder contractions coincided with a reduction in external urethral sphincter (EUS) EMG activity. Following bilateral L₇-S₃ dorsal root transection, electrical stimulation of the pons still elicited the small amplitude bladder contractions, but the larger amplitude, long duration micturition contractions were abolished. During these small evoked bladder contractions, a suppression of EUS activity still occurred following deafferentation, indicating a pontine mediated bladder/EUS synergy. It is concluded that the pons can initiate bladder contractions and coordinated bladder-sphincter activity, but that afferent feedback (via the dorsal roots) is needed to maintain the large amplitude micturition contractions.     

Comparison of the effects of complete and incomplete spinal cord injury on lower urinary tract function as evaluated in unanesthetized rats

In rats, phasic external urethral sphincter (EUS) activity (bursting) is postulated to be crucial for efficient voiding. This has been reported to be lost after spinal cord transection (txSCI), contributing to impaired function. However, anesthesia may confound evaluating EUS activity. We therefore evaluated urodynamic parameters in unanesthetized, restrained rats and compared the effects of txSCI to that of a clinically relevant, incomplete, contusive injury (iSCI) on lower urinary tract function. Adult female rats were subjected to txSCI or standardized iSCI at the T8 vertebral level. As expected, all injured rats were initially unable to void but developed a reflex bladder with time, with iSCI rats recovering more rapidly than txSCI rats. LUT function was evaluated urodynamically at 2 and 6 weeks after injury. In response to infusion of saline into the bladder, controls consistently exhibited coordinated contraction of the bladder and activation of the EUS in a phasic pattern and had a high voiding efficiency (86.4+/-2.5%). Voiding efficiency of iSCI rats was reduced to approximately 57% and txSCI rats to approximately 32%. However, two different patterns of EUS activity during voiding were present in both txSCI and iSCI groups at both time points: (1) rats with phasic EUS activity, similar to controls and (2) those that only exhibited tonic EUS activity during voiding. The former had more normal voiding efficiencies. Thus, phasic EUS activity and the improved voiding efficiency associated with it can occur and can be detected in unanesthetized rats after both incomplete and complete SCI.     

Quantification of external urethral sphincter and bladder activity during micturition in the intact and spinally transected adult rat

The goal of this study was to determine the effect of chronic mid-thoracic spinal cord transection on the time course of external urethral sphincter (EUS) and bladder activity associated with micturition events in the rat. Adult female Sprague–Dawley rats, either spinally intact or transected (T₉–T₁₀), were anesthetized with urethane and set up for continuous flow urodynamic recording of bladder intravesical pressure (BP) and EUS electromyography (EMG). Spinal transections were performed under isoflurane anesthesia 1–8 weeks prior to the terminal experiment. Four major differences between intact and transected rats were observed: 1) While the frequency of micturition events in the intact rat was dependent upon the rate of bladder filling, the bladder contraction and associated EUS activation in transected rats exhibited an intrinsic rhythm that was independent of the rate of bladder filling and post-transection survival time. 2) EUS activation was augmented at the beginning of active bladder contraction in the transected rat, indicating an amplified guarding reflex. 3) Phasic EUS activity at the peak of bladder contraction (EUS bursting) in the intact rat was markedly reduced or absent in the transected rat. 4) The sustained tonic EUS activity following bladder relaxation in the intact rat was absent in the transected rat. These data are discussed in the context of understanding the pathophysiology of spinal cord injury (SCI) induced destrusor-sphincter dyssynergia (DSD).     

Electrophysiological function during voiding after simulated childbirth injuries

During vaginal delivery dual injuries of the pudendal nerve and the external urethral sphincter (EUS), along with other injuries, are correlated with later development of stress urinary incontinence. It is not known how combinations of these injuries affect neuromuscular recovery of the micturition reflex. We investigated the EUS electromyogram (EMG) and the pudendal nerve motor branch potentials (PNMBP) during voiding 4 days, 3 weeks or 6 weeks after injury; including vaginal distension (VD), pudendal nerve crush (PNC), both PNC and VD (PNC + VD), and pudendal nerve transection (PNT); and in controls. Pudendal nerve and urethral specimens were excised and studied histologically. No bursting activity was recorded in the EUS EMG during voiding 4 days after all injuries, as well as 3 weeks after PNC + VD. Bursting activity demonstrated recovery 3 weeks after either VD or PNC and 6 weeks after PNC + VD, but the recovered intraburst frequency remained significantly decreased compared to controls. Bursting results of PNMBP were similar to the EMG, except bursting in PNMBP 4 days after VD and the recovered intraburst frequency was significantly increased compared to controls after PNC and PNC + VD. After PNT, neither the EUS nor the pudendal nerve recovered by 6 weeks after injury. Our findings indicate bursting discharge during voiding recovers more slowly after PNC + VD than after either PNC or VD alone. This was confirmed histologically in the urethra and the pudendal nerve and may explain why pudendal nerve dysfunction has been observed years after vaginal delivery.     

Spinal control of pelvic floor muscles

A prevalent notion in the literature is that the pelvic floor muscles behave as a unitary mass. We examined this proposition experimentally. In spinal cats, we recorded EMG activity from the following pelvic floor muscles: the sphincter ani externus (SAE), the abductor caudae internus (coccygeus), and the levator ani (pubiocaudalis) muscles. The epaxial sacrocaudalis dorsalis lateralis muscle was also exposed and prepared for recording. Electrical stimulation of S2 ventral roots elicited twitch responses of the sphincter ani externus and of the sacrocaudalis dorsalis lateralis muscles. Stimulation of S3 and Cx1 ventral roots elicited responses in the other two muscles studied, the levator ani and abductor caudae internus. Thus a clear segregation of the segmental motor neuron pools innervating the different pelvic floor muscles was demonstrated. The various muscles of the pelvic floor region could be reflexly activated either individually or as a mass unit depending on the intensity of stimulation. Tactile or electrical stimulation of pudendal regions on either side of the body elicited responses of the sphincter ani externus. In contrast, activation of the levator ani and abductor caudae internus muscles could be lateralized: tactile or electrical stimulation of the dorsolateral surfaces at the base of the tail region elicited ipsilateral responses from these muscles. Section of one pudendal nerve did not alter the level of tonic activity (2 to 4/s) of the sphincter ani externus. However, bilateral section of the pudendal nerve entirely abolished both tonic activity and phasic responsiveness of the SAE without affecting the activity of the levator ani and abductor caudae internus muscles. Pudendal nerve stimulation elicited only polysynaptic reflex responses from S2 ventral roots. The results presented show that the neural apparatus of the striated musculature of the pelvic floor is capable of activating individually the different muscles that make up the system, and that the sphincter ani externus from one side, and muscles that conform the diaphragm pelvis from the other, are subserved by different neuronal circuits.     

Neurophysiology of the neurogenic lower urinary tract disorders.

The nervous system structures involved in the control of the lower urinary tract (LUT) are usually divided using a neuroanatomical classification system into suprapontine, pontine, spinal and sacral. In all patients with LUT symptoms, after exclusion of local causes, a nervous system disorder needs to be considered. For the diagnosis of neurogenic LUT disorders, in addition to clinical assessment, neurophysiologic testing might be useful. Imaging and other laboratory studies (e.g., cystometry) often provide relevant additional information. Neurophysiologic tests are more useful in patients with sacral compared with suprasacral disorders. Although in patients with LUT disorders external urethral sphincter (EUS) electromyography (EMG) would seem the most appropriate, anal sphincter EMG is the single most useful diagnostic test, particularly for focal sacral lesions, and atypical parkinsonism. Another clinically useful method that tests the sacral segments, and complements EMG, is the sacral (penilo/clitoro-cavernosus) reflex. Kinesiologic EMG is useful to demonstrate detrusor sphincter dyssynergia (i.e., increased EUS activity during bladder contraction), which is particularly common in spinal cord disease. Somatosensory evoked potential (SEP) and motor evoked potential (MEP) studies (cortical and lumbar) may be useful to diagnose clinically silent central lesions. MEP, in addition, seems to be very promising in research into cortical excitability. Theoretically, cortical SEP on bladder/urethra stimulation would be much more useful than pudendal SEP because it tests thin nerve afferents from the pelvic viscera. However, the utility of this technique is limited by technical difficulties, which can be partially overcome by the concomitant recording of a palmar sympathetic skin response (SSR). SSR recorded from the saddle region is also useful for testing the lumbosacral sympathetic system. Although the technique of detrusor EMG has been recently described in humans, a clinically useful test for evaluating the sacral parasympathetic system, which is crucial for LUT functioning, is still lacking.     

Comparison of the motor discharge to the voluntary sphincters of continence in the rat

Background The rat external anal sphincter (EAS) and external urethral sphincter (EUS) are voluntary muscles of continence that can display similar synchronous electromyographic (EMG) activity patterns. However, the two sphincters are quite different in structure and function. The EUS is a fast twitch muscle and contains fibers expressing type 2B myosin. In contrast, the EAS exhibits slower kinetics and lacks type 2B fibers. This striking contrast in kinetics and fiber type profiles may be shaped by differences in the basal motor drive that each sphincter receives. Methods A double EMG approach was used to obtain spontaneously active single motor unit action potentials from the EUS and EAS simultaneously and compare their basal discharge frequencies in urethane anaesthetized rats. Key Results The basal firing rates of motor units of the EUS and EAS were not significantly different (3.9 ± 0.9 Hz vs. 3.1 ± 1.6 Hz, respectively, n = 7 animals, P = 0.32, paired Student’s t‐test). However, auto‐correlogram analysis showed that EUS is driven by neurons with faster instantaneous firing frequencies: 30.5 ± 2.4 Hz vs 14.3 ± 0.9 Hz in the EAS (P = 0.03, paired Student’s t‐test). Conclusions & Inferences The oscillator(s) driving the EUS operate(s) at a frequency twice that of the EAS. This may explain the presence of type 2B fibers in the EUS. In the inter‐micturition periods no cross correlation was found in motor discharge to the sphincters suggesting that the two muscles do not share a common central drive to sustain the continent tonus of the two outlet tracts.     

Functional recovery in primates with brachial plexus injury after spinal cord implantation of avulsed ventral roots.

Intraspinal replantation of avulsed spinal nerve roots as a surgical treatment for motor deficits after severe brachial plexus injury was investigated in primates. Under general anaesthesia hemi-laminectomy was performed in cynomolgus monkeys (Macaca fascicularis). Ventral roots within the brachial plexus were then avulsed by traction and subsequently implanted into the ventrolateral aspect of the spinal cord. No dysfunction in the long fibre tracts was seen following surgery. Postoperatively there was a flaccid paralysis of the arm on the lesioned side. Severe atrophy developed within 5-7 weeks in the muscles supplied by the avulsed roots and EMG revealed denervation activity. Two to three months after surgery there were EMG signs of reinnervation, which were shortly followed by evidence of clinical recovery. A gradual improvement in the function of the affected arm occurred and the animals' motor behaviour normalised. One year after surgery there was a full range of motion in the arm, but the EMG activity in the reinnervated muscles at maximal force was reduced. Tracing of regenerated motor neurons with horseradish peroxidase (HRP) injected into the biceps muscle revealed retrogradely labelled motor neurons confined to the ipsilateral ventral horn. It was concluded that intraspinal replantation of avulsed ventral roots in primates significantly promotes motor recovery in the muscles supplied by the lesioned spinal cord segments.     

Lower urinary tract function in patients with pituitary adenoma compressing hypothalamus

BACKGROUND: The micturition reflex is under the tonic influence of suprapontine structures including the anteromedial frontal cortex, basal ganglia, and hypothalamus. However, there have been few reports about the role of the hypothalamus on the lower urinary tract (LUT) function in humans. OBJECTIVE: To investigate LUT function in patients with pituitary adenomas. METHODS: Urodynamic studies were carried out in three patients with LUT symptoms who had pituitary adenomas extending upwards to the hypothalamus. RESULTS: All three male patients (age 28 to 62 years) developed LUT symptoms (urinary urgency and frequency (3); urinary incontinence (3); voiding difficulty and retention (2)) along with weight loss, psychiatric symptoms, unsteady gait, and/or visual disturbances. One had the syndrome of inappropriate secretion of antidiuretic hormone, but none had diabetes insipidus. Two had resection of the tumour and subsequent radiation therapy, but LUT dysfunction persisted. The third patient had partial resection of the tumour to ameliorate hydrocephalus. Urodynamic studies showed detrusor overactivity during the storage phase in all patients; during the voiding phase there was underactive detrusor in two and non-relaxing sphincter in one. CONCLUSIONS: Hypothalamic lesions can cause severe LUT dysfunction in both the storage and voiding phases of micturition. This may reflect the crucial role of the hypothalamus in regulating micturition in humans.     

Surface EMG activity during REM sleep in Parkinson's disease correlates with disease severity

ObjectivesOver 40% of individuals with Parkinson's disease (PD) have rapid eye movement sleep behavior disorder (RBD). This is associated with excessive sustained (tonic) or intermittent (phasic) muscle activity instead of the muscle atonia normally seen during REM sleep. We examined characteristics of manually-quantitated surface EMG activity in PD to ascertain whether the extent of muscle activity during REM sleep is associated with specific clinical features and measures of disease severity.MethodsIn a convenience sample of outpatients with idiopathic PD, REM sleep behavior disorder was diagnosed based on clinical history and polysomnogram, and severity was measured using the RBD sleep questionnaire. Surface EMG activity in the mentalis, extensor muscle group of the forearms, and anterior tibialis was manually quantitated. Percentage of REM time with excessive tonic or phasic muscle activity was calculated and compared across PD and RBD characteristics.ResultsAmong 65 patients, 31 had confirmed RBD. In univariate analyses, higher amounts of surface EMG activity were associated with longer PD disease duration (srho = 0.34; p = 0.006) and greater disease severity (p < 0.001). In a multivariate regression model, surface EMG activity was significantly associated with RBD severity (p < 0.001) after adjustment for age, PD disease duration, PD severity and co-morbid sleep abnormalities.ConclusionSurface EMG activity during REM sleep was associated with severity of both PD and RBD. This measure may be useful as a PD biomarker and, if confirmed, may aid in determining which PD patients warrant treatment for their dream enactment to reduce risk of injury.     

Clozapine inhibits micturition parameters and the external urethral sphincter during cystometry in anesthetized rats

Clozapine therapy has been associated with a high degree of urinary disturbances. The purpose of this study is to examine the effect of clozapine on urodynamic parameters and on the activity of the external urethral sphincter in anesthetized rats. Single cystometrograms (CMG) were performed on urethane-anesthetized female Sprague-Dawley rats, while also recording the EMG from the external urethral sphincter. Clozapine (0, 0.1, 1, 10 mg/kg) was administered intravenously. In addition, the peripheral end of the pudendal nerve was stimulated in order to determine if clozapine was exerting peripheral effects directly on the external urethral sphincter. Clozapine increased the bladder capacity while reducing the micturition volume thus resulting in a marked increase in the residual volume. The pressure threshold was increased but the peak pressure during contraction remained unchanged. The expulsion time and contraction time were decreased and the amplitude of the high frequency oscillations (HFO) seen during the expulsion phase were markedly reduced and even abolished. The EMG from the external urethral sphincter also showed marked decreases after clozapine, and the bursting pattern seen during HFO was abolished. Clozapine had no effect on the activity elicited from electrical stimulation of the pudendal nerve. Clozapine inhibits several urodynamic parameters and inhibits the activity of the external urethral sphincter in anesthetized rats. These effects may help explain the urinary disturbances reported in the clinical literature.     

Interaction between D2 dopaminergic and glutamatergic excitatory influences on lower urinary tract function in normal and cerebral-infarcted rats

Previous studies showed that bladder hyperactivity after cerebral infarction in Sprague-Dawley (SD) rats was mediated in part by D2 dopaminergic and NMDA glutamatergic mechanisms. In the present experiments, the interaction between dopaminergic and glutamatergic excitatory mechanisms in the control of bladder and external urethral sphincter (EUS) reflexes was investigated in urethane-anesthetized sham-operated (SO) and cerebral-infarcted (CI) SD rats. Occlusion of the left middle cerebral artery or a sham operation was performed under halothane anesthesia. Two hours after either of the two procedures, rats were anesthetized with urethane. Dizocilpine, an N-methyl-d-aspartate (NMDA) glutamatergic antagonist, was administered intravenously in doses of 0.3 or 3 mg/kg to CI rats and 3 mg/kg to SO rats. These doses completely inhibited bladder and EUS activity. The effects of apomorphine (a dopamine agonist with greater efficacy at D2 than D1 receptors) or quinpirole (a selective D2 dopamine receptor agonist) were examined on the dizocilpine-induced depression of bladder contractions and EUS EMG activity. Apomorphine did not antagonize the dizocilpine depression of EUS activity, but it did reestablish the micturition reflex after dizocilpine blockade and did increase the amplitude of bladder contractions and voided volume in a dose-dependent manner (0.0001-10 mg/kg, iv), in both CI rats and SO rats pretreated with dizocilpine. There were no differences between SO rats and CI rats in the apomorphine responses in rats pretreated with doses of 0.3 or 3 mg/kg dizocilpine. A larger dose of dizocilpine (10 mg/kg) did not affect the bladder contractions after apomorphine administration. Quinpirole (0.001-1 mg/kg, iv) also partially reversed the dizocilpine depression of bladder activity in SO and CI rats. These results indicate that NMDA glutamatergic and D2 dopaminergic mechanisms exert independent excitatory influences on bladder activity in both SO and CI rats. D2 dopamine receptor agonists can reverse the effect of NMDA receptor blockade on bladder activity but were ineffective in reversing the block of sphincter activity.     

Encoding of motor parameters by corticomotoneuronal (CM) and rubromotoneuronal (RM) cells producing postspike facilitation of forelimb muscles in the behaving monkey

This paper compares the properties of corticomotoneuronal (CM) and rubromotoneuronal (RM) cells identified by postspike facilitation (PSF) of rectified EMG activity in the awake monkey. The postspike effects of CM and RM cells in flexors and extensors of the wrist and fingers have been determined, as have the discharge properties of these cells in relation to alternating ramp-and-hold wrist movements. The characteristics of postspike facilitation and postspike suppression (PSS) were similar for RM and CM cells. The magnitude of RM-PSF was weaker than CM-PSF and RM cells showed a stronger preference for facilitation of extensor muscles than CM cells. As with CM cells, the onset of discharge in RM cells preceded the onset of EMG activity in their target muscles. Tonic discharge related to static torque was more prominent in CM cells, whereas phasic discharge was more prominent in RM cells; however, many RM cells showed some tonic activity weakly related to static torque. We conclude that CM and RM cells share many common features; however, RM cells are concerned primarily with the dynamics of muscle contraction.     

The role of 5-HT(1A) receptors in control of lower urinary tract function in cats

In the present study, the role of 5-HT(1A) receptors in control of lower urinary tract function in cats was examined using 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) as agonists and WAY100635 and LY206130 as antagonists. Bladder function was assessed using cystometric infusion of saline or 0.5% acetic acid to produce bladder irritation. External urethral sphincter (EUS) function was assessed using electromyographic (EMG) recordings of activity recorded during cystometry or by recording electrically evoked pudendal reflexes. Both 5-HT(1A) receptor agonists caused dose-dependent decreases in bladder activity and increases in EUS EMG activity under conditions of acetic acid infusion. 5-HT(1A) receptor antagonists reversed both the bladder-inhibitory and sphincter-facilitatory effects. Thus, 5-HT(1A) receptor activation can have opposite effects on nociceptive afferent processing depending upon the efferent response being measured. During saline infusion of the bladder, 8-OH-DPAT produced moderate inhibition of bladder activity and had no significant effect on sphincter electromyographic (EMG) activity. 8-OH-DPAT either had no effect, or inhibited, low-threshold electrically evoked pudendal reflexes. These findings indicate that 5-HT(1A) receptor stimulation is inhibitory to bladder function in cats, especially under conditions where the bladder is hyperactive due to irritation. Furthermore, these bladder-inhibitory effects are the exact opposite of the bladder-excitatory effects of 8-OH-DPAT reported in rats. 5-HT(1A) receptor stimulation increases EUS motoneuron activity when driven by nociceptive bladder afferent inputs but not when driven by non-nociceptive afferent inputs. In summary, 5-HT(1A) receptor agonists facilitate a nociceptor-driven spinal reflex (sphincter activity) but inhibit a nociceptor-driven supraspinal reflex (micturition). This pattern of activity would facilitate urine storage and may be important under 'fight-or-flight' conditions when serotonergic activity is high.     

The locus coeruleus–norepinephrine system as pacemaker of attention – a developmental mechanism of derailed attentional function in autism spectrum disorder

Children with autism spectrum disorder (ASD) exhibit diminished visual engagement to environmental stimuli. Aberrant attentional function provides an explanation by reduced phasic alerting and orienting to exogenous stimuli. We review aberrant attentional function (alerting, orienting and attentional control) in children with ASD as studied by neurocognitive and neurophysiological tasks as well as magnetic resonance imaging studies. The locus coeruleus–norepinephrine (LC–NE) system is outlined as a pacemaker of attentional function. The LC–NE system regulates adaptive gain in synaptic signal transmission, which moderates phasic alerting (‘promoting’) and the activation of the ventral frontoparietal attention network within orienting (‘permitting’). In children with ASD, atypical LC–NE activity is proposed as underlying mechanism of aberrant attentional function. It may manifest as (i) increased tonic activity with reduced phasic reactivity to exogenous stimuli, (ii) attenuated bottom‐up signalling mitigating salience and predictive reward attribution during phasic alerting, and (iii) reduced activation of the ventral frontoparietal attention system attenuating orienting to exogenous stimuli. Increased tonic pupil dilation and aberrant pupil reactivity are discussed as indicators of atypical LC–NE activity. Pupillometry is outlined as feasible method to assess alerting, orienting and attentional control that can be dissected from the pupil dilation time course. In children with ASD, aberrant attentional function through atypical LC–NE activity is proposed as developmental mechanism leading to reduced social attention as well as social interaction and communication impairments.     

Firing patterns of micturition-related neurons in the pontine storage centre in cats

The pontine storage centre (PSC) and the pontine micturition centre (PMC) are known to be critical for urinary filling and emptying, respectively. In the present study, firing patterns of 45 neurons in the PSC area where electrical stimulation induced inhibition of the micturition reflex were analyzed in 20 male decerebrated and paralyzed cats. The electrically determined PSC area was widespread in the dorsolateral pontine reticular formation (P0-P4), ventrolateral to the PMC. Four major types of neurons were detected according to urinary storage/micturition cycles: tonic storage neurons (38%), phasic storage neurons (40%), tonic micturition neurons (9%) and phasic micturition neurons (13%). These four types of neurons were intermingled in the PSC. However, the tonic and phasic micturition neurons tended to be located within a limited area (P2-P3). These neurons were further classified into augmenting, constant and decrementing firing patterns. Some increased their firing prior to the storage/micturition phase initiation. Such preceding pattern was more frequently found in the tonic neurons than in the phasic neurons. In conclusion, the PSC neurons with diverse heterogeneous discharge patterns suggest that these neurons may organize a complex neuronal circuitry, which is critical in the neural control of the urinary continence.     

Colonic transit time, sphincter EMG, and rectoanal videomanometry in multiple system atrophy.

Both constipation and fecal incontinence are prominent lower gastrointestinal tract (LGIT) dysfunctions that occur frequently in multiple system atrophy (MSA). We investigated the mechanism of constipation and fecal incontinence in MSA. Colonic transit time (CTT), sphincter electromyography (EMG), and rectoanal videomanometry were performed in 15 patients with MSA (10 men, 5 women; mean age, 63.5 years; mean duration of disease, 3 years; decreased bowel frequency [< 3 times a week] in 9; difficulty in expulsion in 11; fecal incontinence in 3) and 10 age-matched healthy control subjects (7 men and 3 women; mean age, 62 years; decreased bowel frequency in 2; mild difficulty in expulsion in 2; fecal incontinence in none). Compared to the control subjects, MSA patients had significantly prolonged CTT in the rectosigmoid segment and total colon. Sphincter EMG showed neurogenic motor unit potentials in none of control subjects but in 93% of MSA patients. At the resting state, MSA patients showed a lower anal squeeze pressure (external sphincter weakness) and a smaller increase in abdominal pressure on coughing. During rectal filling, MSA patients showed smaller amplitude in phasic rectal contraction, which was accompanied by an increase in anal pressure that normally decreased, together with leaking in 3 patients. During defecation, most MSA patients could not defecate completely and had larger postdefecation residuals. MSA patients had weak abdominal strain, smaller rectal contraction on defecation, and larger anal contraction on defecation (paradoxical sphincter contraction on defecation), although these differences were not statistically significant. These findings in MSA patients were similar to those in Parkinson's disease patients in our previous study, except for the sphincter denervation and weakness in MSA. Constipation in MSA most probably results from slow colonic transit, decreased phasic rectal contraction, and weak abdominal strain, and fecal incontinence results from weak anal sphincter due to denervation. The responsible sites for these dysfunctions seem to be both central and peripheral nervous systems that regulate the LGIT.     

Decreased phasic EMG activity during rapid eye movement sleep in treatment‐naïve Parkinson's disease: Effects of treatment with levodopa and progression of illness

Rapid eye movement (REM) sleep behavior disorder (RBD) is frequently associated with Parkinson's disease (PD) and may anticipate its diagnosis by several years. We assessed the presence of motor dyscontrol during REM sleep in treatment‐naïve PD patients and investigated the putative effect of levodopa (L ‐dopa) treatment on motor activity. Overnight sleep studies were performed on 15 previously untreated PD patients and 14 controls at baseline, again after a 3‐ to 9‐month treatment period with a low dose of L ‐dopa, and 2 to 5 days after treatment discontinuation (in 8 patients). No differences in sleep parameters were observed across groups or treatment conditions. None of the patients met criteria for RBD at baseline, whereas 5 patients were symptomatic at the time of the second sleep study. A quantitative analysis of electromyographic (EMG) activity during REM sleep showed a lower phasic twitching activity in untreated PD than in controls. However, an increase in both phasic twitching and tonic activity was found after treatment with L ‐dopa. Discontinuation of treatment resulted in a return to pretreatment values of phasic but not of tonic EMG activity. Thus, the increase in phasic activity seems to depend on the effects of L ‐dopa, whereas the increase in tonic EMG activity during REM sleep might be caused by other factors such as the progression of disease. Potential implications for the understanding of the relationship between RBD and PD are discussed. © 2002 Movement Disorder Society     

Modulation of the bulbocavernosus reflex during voiding: loss of inhibition in upper motor neuron lesions

The bulbocavernosus reflex (BCR) is a sacral segmental reflex which is suppressed throughout most of micturition. The BCR was evaluated by recording the associated EMG activity using a concentric needle electrode placed in the external urethral sphincter. The influence of the central nervous system (CNS) on the BCR was studied in 29 neurologically normal individuals and in 33 patients with upper motor neuron (UMN) lesions and voiding dysfunction. Ninety percent (26/29) of the neurologically normal patients did not have a BCR during most of micturition. By comparison, all the patients with an UMN lesion had a positive BCR beginning early during voiding. The finding of suprasegmental modulation of the BCR during voiding demonstrated by external urethral sphincter EMG was a more sensitive although slightly less specific sign of UMN bladder dysfunction than detrusor sphincter dyssynergia; uninhibited bladder contractions were neither sensitive nor specific for UMN lesions.     

A spatio-temporal analysis of motoneuron survival, axonal regeneration and neurotrophic factor expression after lumbar ventral root avulsion and implantation

Reimplantation of avulsed rat lumbar spinal ventral roots results in poor recovery of function of the denervated hind limb muscles. In contrast, reimplantation of cervical or sacral ventral roots is a successful repair strategy that results in a significant degree of regeneration. A possible explanation for this difference could be that following lumbar root avulsion, axons have to travel longer distances towards their target muscles, resulting in prolonged denervation of the distal nerve and a diminished capacity to support regeneration. Here we present a detailed spatio-temporal analysis of motoneuron survival, axonal regeneration and neurotrophic factor expression following unilateral avulsion and implantation of lumbar ventral roots L3, L4, and L5. Reimplantation prolongs the survival of motoneurons up to one month post-lesion. The first regenerating motor axons entered the reimplanted ventral roots during the first week and large numbers of fibers gradually enter the lumbar plexus between 2 and 4 weeks, indicating that axons enter the reimplanted roots and plexus over an extended period of time. However, motor axon counts show that relatively few axons reach the distal sciatic nerve in the 16 week post-lesion period. The observed initial increase and subsequent decline in expression of glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor correlate with the apparent spatio-temporal decline in the regenerative capacity of motor axons, indicating that the distal nerve is losing its capacity to support regenerating motor axons following prolonged denervation. These findings have important implications for future strategies to promote long-distance regeneration through distal, chronically denervated peripheral nerves.