The subthalamic activity and striatal monoamine are modulated by subthalamic stimulation.

AIMS: Not all the mechanisms by which subthalamic nucleus deep brain stimulation (STN-DBS) alleviates parkinsonian symptoms have been clarified as yet. The levels of striatal monoamine and the subthalamic beta activity might contribute to its efficacy. However, their direct relationship is unclear. We aimed to examine the correlation between the striatal monoamine and the STN beta activity induced by STN-DBS. EXPERIMENTAL PROCEDURES: Experiments were performed under urethane anesthesia in normal (n=4) and 6-hydroxydopamine hemi-lesioned Parkinson's disease (PD) model rats (n=5). STN-DBS was applied to the left STN, and local field potential (LFP) was recorded before and after STN-DBS. Striatal extracellular fluid was collected before, during, and after STN-DBS. Spectral analysis of STN-LFP was performed, and the levels of monoamine were measured. RESULTS: The levels of 3-4-dihydroxyphenylacetic acid (DOPAC) were significantly decreased after the cessation of stimulation in PD model rats. The levels of none of the monoamines were significantly affected in normal rats. The STN beta power was significantly elevated after the cessation of stimulation in normal rats but was significantly decreased in PD model rats. The STN beta power and the levels of DOPAC and 5-HT was positively correlated in PD model rats, whereas the levels of dopamine and 5-HT showed positive correlation and the levels of DOPAC and Homovanillic acid (HVA) showed negative correlation in normal rats. CONCLUSION: STN-DBS could decrease the levels of DOPAC and the STN beta power in a PD model rat. The STN beta power and the levels of striatal monoamine might be differentially correlated between normal and PD model rats.

Pelvic organ dysfunction is more prevalent and severe in MSA-P compared to Parkinson's disease.

AIMS: It is usually difficult to distinguish between idiopathic Parkinson's disease (PD) and parkinsonian-type multiple system atrophy (MSA-P) in the early stage. However, it is important to make a careful early-stage diagnosis. Therefore, we determined whether an examination of pelvic organ dysfunction would be helpful to distinguish between PD and MSA-P. METHODS: We recruited 61 patients with PD and 54 patients with MSA-P who were examined at our neurology clinic. The mean ages of the patients with PD and MSA-P were 67 and 64 years, respectively. The mean disease duration of both groups was 3.2 years. We administered a questionnaire on pelvic organ dysfunction to the PD and MSA-P groups. The questionnaire had sections focusing on bladder, bowel, and sexual function. Dysfunction, as described in the responses, was evaluated as normal, mild (>once a month), moderate (>once a week), or severe (>once a day). The Mann-Whitney U-test was used for statistical analysis. RESULTS: Compared with the PD group, the prevalence and severity of pelvic dysfunction in the MSA-P group was significantly higher for urinary urgency (MSA-P 76%, PD 58%, P<0.05), retardation in initiating urination (79%, 48%, P<0.05), prolongation in urination (79%, 72%, P<0.05), and constipation (58%, 31%, P<0.05). The quality-of-life index among pelvic organ dysfunctions indicated that urinary and bowel function was significantly more impaired in the MSA-P group than in the PD group. CONCLUSIONS: Urinary urgency, retardation in initiating urination, prolongation in urination, and constipation are more prevalent and severe in MSA-P compared to PD.

Neurologic urinary incontinence.

INTRODUCTION: This manuscript summarizes the work of Committee 10 on neurologic bladder and bowel of the International Consultation on Incontinence in 2008-2009. As the data are very large the outcome is presented in different manuscripts. This manuscript deals with neurologic urinary incontinence. METHODS: Through in debt literature review all aspects of neurological urinary incontinence were studied for levels of evidence. Recommendations for diagnosis and treatment, and for future research were made. RESULTS: Pathophysiology was summarized for different levels of lesions. For epidemiology, specific diagnostics, conservative treatment and surgical treatment of neurologic urinary incontinence, levels of evidence and grades of recommendation were made following ICUD criteria. CONCLUSIONS: Though data are available that advice and guide in the management of urinary incontinence in neurologic patients, not many data have a high level of evidence or permit a high grade of recommendation. More and well-structured research is needed.

Neurologic fecal incontinence.

INTRODUCTION: This manuscript summarizes the work of Committee 10 on neurologic bladder and bowel of the International Consultation on Incontinence in 2008-2009. As the data are very large the outcome is presented in different manuscripts. This manuscript deals with neurologic fecal incontinence (FI). METHODS: Through in debt literature review all aspects of neurologic urinary and FI were studied for levels of evidence. Recommendations for diagnosis and treatment, and for future research were made. RESULTS: Pathophysiology was summarized for different levels of lesions. For epidemiology, specific diagnostics, conservative treatment, and surgical treatment of neurologic FI levels of evidence and grades of recommendation were made. CONCLUSIONS: Though data are available that advice and guide in the management of FI in neurologic patients, not many data are with a high level of evidence or high grade of recommendation. More and well-structured research is needed.

Reduced perfusion in the anterior cingulate cortex of patients with pure autonomic failure: an 123I-IMP SPECT study.

BACKGROUND: Pure autonomic failure (PAF) is a selective peripheral disorder in which Lewy bodies form within the autonomic ganglia. Patients with this disorder usually have no central lesions; however, chronic autonomic failure may secondarily affect the central nervous system. This study evaluated brain perfusion in patients with PAF by using N-isopropyl-p-(123)I iodoamphetamine ((123)I-IMP) single photon emission computed tomography (SPECT). METHODS: Six patients with PAF (all men; mean (SD) age 68+/-5 years) who had experienced autonomic symptoms for more than 5 years and six age-matched healthy control subjects (all men; mean (SD) age 67+/-5 years) were included in this study. The regions of interest (ROI) on spacially normalized (123)I-IMP SPECT images were automatically computed for both groups. RESULTS: Perfusion of the dorsal anterior cingulate cortex was decreased in the PAF group compared with the healthy control group (0.93 vs 1.01; p<0.001). In the other brain regions measured, there was no significant difference in regional perfusion between the two groups. CONCLUSIONS: The dorsal anterior cingulate cortex is poorly perfused and may be functionally altered in patients with PAF. The reduced perfusion in such individuals may be a secondary change that results from chronic autonomic failure.

Biphasic effect of apomorphine, an anti-parkinsonian drug, on bladder function in rats.

The effects of anti-parkinsonian drugs on bladder function have been controversial; namely, some aggravated while others alleviated bladder dysfunction in patients with Parkinson disease. These studies, however, did not consider the dose- and time-dependent effects. Therefore, we investigated these effects of apomorphine, an anti-parkinsonian drug and a nonselective dopamine receptor agonist, on the bladder function using normal conscious rats. Consecutive cycles of micturition were analyzed for 30-min periods before and after (over a 4-h period) s.c. administration of a single dose of 0.01 (low), 0.05 (medium), 0.5 (high) mg/kg of apomorphine or saline to the rats. Apomorphine administration produced various effects in relevant urodynamic parameters, although the monitored parameters remained unchanged in saline-administered rats. During filling, low-dose apomorphine induced initial decreases in voiding frequency (VF; defined as the number of voidings during a 15-min period). However, medium- and high-dose apomorphine dose-dependently induced initial increases in VF, and was followed by decreases in VF. These doses also induced initial increase in threshold pressure. During voiding, low-dose apomorphine induced initial increases in micturition volume (MV), which reflected an increase in bladder capacity (BC). However, medium- and high-dose apomorphine dose-dependently induced initial decreases in MV, and was followed by increases in MV. These doses also dose-dependently induced an initial increase in maximum bladder contraction pressure during the early phase after administration. The present study demonstrated that apomorphine displayed a dose- and time-dependent biphasic effect on the normal bladder filling function. These pharmacodynamic characteristics of apomorphine could be applicable to other anti-parkinsonian drugs such as levodopa and nonselective dopamine receptor agonists, and may account for the previous reported conflicting effects of anti-parkinsonian drugs on bladder dysfunction in patients with Parkinson disease, although it needs to be evaluated in disease status.

Bladder and bowel dysfunction in Parkinson's disease.

Bladder dysfunction (urinary urgency/frequency) and bowel dysfunction (constipation) are common non-motor disorders in Parkinson's disease (PD). In contrast to motor disorder, the pelvic autonomic dysfunction is often non-responsive to levodopa treatment. Brain pathology mostly accounts for the bladder dysfunction (appearance of overactivity) via altered dopamine-basal ganglia circuit, which normally suppresses the micturition reflex. In contrast, peripheral enteric pathology mostly accounts for the bowel dysfunction (slow transit and decreased phasic contraction) via altered dopamine-enteric nervous system circuit, which normally promotes the peristaltic reflex. In addition, weak strain and paradoxical anal contraction might be the results of brain pathology. Pathophysiology of the pelvic organ dysfunction in PD differs from that in multiple system atrophy; therefore it might aid the differential diagnosis. Drugs to treat bladder dysfunction in PD include anticholinergic agents. Drugs to treat bowel dysfunction in PD include dietary fibers, peripheral dopaminergic antagonists, and selective serotonergic agonists. These treatments might be beneficial not only in maximizing patients' quality of life, but also in promoting intestinal absorption of levodopa and avoiding gastrointestinal emergency.

Urinary retention due to an isolated sacral root injury caused by sacral fracture.

STUDY DESIGN: A case report. SETTING: Urodynamic laboratory in a university hospital, Chiba, Japan. CASE REPORT: A young woman who suffered from urinary retention following a skiing accident. A sacral X-ray (lateral view) revealed an S2-3 sacral fracture. The patient gradually regained the ability to urinate. At 3 months after the accident, she still suffered difficult urination, although her neurological findings were normal. A urodynamic study showed an acontractile detrusor and a neurogenic sphincter electromyogram (EMG), together indicative of isolated sacral nerve injury. CONCLUSIONS: It was postulated that the S2-3 sacral fracture had led to bilateral traction of the S2-3 nerve roots, producing transient bladder paralysis (parasympathetic fibers) and incomplete sphincter paresis (somatic fibers). Sacral fracture is also of high clinical suspicion for urinary retention in frail elderly people, because it can result from simple falls.

Wolfram syndrome presenting marked brain MR imaging abnormalities with few neurologic abnormalities.

Wolfram syndrome is a rare autosomal recessive disorder featuring diabetes insipidus, diabetes mellitus, optic atrophy, and deafness; DIDMOAD is a commonly accepted anonym for this disorder. We describe a 35-year-old man with Wolfram syndrome, who had marked atrophy of the brain stem, middle cerebellar peduncle, and cerebellum. Despite these MR imaging findings involving the pontocerebellar tract, the patient had no neurologic abnormalities suggesting dysfunction of the brain stem or cerebellum. Patients with Wolfram syndrome may have discrepancies between neurologic and radiologic findings.

Urinary retention can be the sole initial manifestation of acute myelitis.

Urinary retention is a frequent feature in patients with acute myelitis (AM). We here describe the result of a survey of 32 consecutive AM patients as to what extent of AM patients initially present with micturition disturbance. Among those, 3 patients (9%) were shown to have urinary retention as the initial sole manifestation, which was followed by dysesthesia of foot in 3 and leg weakness in 1; and the average interval between micturition disturbance and these second-appearing symptoms/signs was 11 days (8-15 days). Although initial presentation of urinary retention was not common, occurring in only 9% of all the AM patients, clinically it has relevance because patients who suffer urinary retention but have no obvious neurological symptoms may first see general physicians or urologists. In those patients, when obstructive disease has been excluded, AM should be considered.

Effects of electrical stimulation of the raphe area on the micturition reflex in cats.

The raphe nucleus has a variety of physiological functions, including emotion, regulation of skeletal muscle motoneurons, spinal transmission of nociceptive signals, sleep, respiration, gastric motility, and cardiovascular function. Recent evidence has shown that centrally administered serotonin has modulatory effects on micturition function, and that decreased brain serotonin might underlie depression and an overactive bladder. We applied high-frequency stimulation (HFS; 0.2-ms duration, 100 Hz) in the raphe nucleus and the adjacent midline area in 20 supracollicular decerebrate cats, which mostly elicited inhibition of the micturition reflex. The effective amplitude of the electrical stimulation for evoking inhibitory responses was less than 50 muA. We also examined single neuronal activities in the raphe nucleus in response to isovolumetric spontaneous micturition reflexes. In total, 79 neurons were recorded in the raphe nucleus that were related to urinary storage/micturition cycles. Of the neurons recorded, the most common were tonic storage neurons (48%), followed by tonic micturition neurons (28%), phasic storage neurons (18%), and phasic micturition neurons (6%). In addition to the tonic/phasic as well as storage/micturition classification, the neurons showed diverse discharge patterns: augmenting, constant and decrementing, with the constant discharge pattern being most common. Among neurons in the raphe nucleus, the neurons with a decrementing discharge pattern were concentrated in the rostral portion, whereas the augmenting and constant neurons existed diffusely. The storage and micturition neurons were intermingled in the rostral portion, whereas they were separate in the caudal portion. In conclusion, the results of the present study indicate that HFS of the raphe area inhibits the micturition reflex and that there are micturition-related neuronal firings in the raphe area in cats, suggesting that the raphe nucleus is involved in neural control of micturition.

When is Onuf's nucleus involved in multiple system atrophy? A sphincter electromyography study.

BACKGROUND: External anal sphincter (EAS) electromyography (EMG) abnormalities can distinguish multiple system atrophy (MSA) from Parkinson's disease in the first five years after disease onset. However, the prevalence of the abnormalities in the early stages of MSA is unknown. OBJECTIVES: To present EAS-EMG data in the various stages of MSA. METHODS: 84 patients with "probable" MSA were recruited (42 men, 42 women; mean age 62 years (range 47 to 78); mean disease duration 3.2 years (0.5 to 8.0; <1 year in 25%); 50 cerebellar form (MSA-C), 34 parkinsonian form (MSA-P)). EAS motor unit potential (MUP) analysis and EMG cystometry were carried out in all patients. RESULTS: The overall prevalence of neurogenic change of the EAS MUP was 62%-52% in the first year after disease onset, increasing to 83% by the fifth year (p<0.05); it also increased with severity of gait disturbance (p<0.05), storage and voiding disorders, and detrusor sphincter dyssynergy (NS). The neurogenic change was not correlated with sex, age, MSA-P/C, postural hypotension, constipation, erectile dysfunction in men, underactive or acontractile detrusor, or detrusor overactivity. In 17 incontinent patients without detrusor overactivity or low compliance, urinary incontinence was more severe in those with neurogenic change than in those without (p<0.05). CONCLUSIONS: Involvement of Onuf's nucleus in MSA is time dependent. Before the fifth year of illness, the prevalence of neurogenic change does not seem to be high, so a negative result cannot exclude the diagnosis of MSA.

Striatal dopamine level increases in the urinary storage phase in cats: an in vivo microdialysis study.

Parkinson's disease is a common neurodegenerative disease that shows not only movement disorder, but also profound urinary dysfunction. Bladder hyperactivity is the major urodynamic abnormality. Therefore, the basal ganglia have been thought to modulate the micturition reflex. In six male adult cats under ketamine anesthesia, in which spontaneous isovolumetric micturition reflexes had been generated, we measured levels of striatal dopamine, in micturition and storage phases, using in vivo microdialysis. The striatal dopamine level significantly increased in the storage phase as compared with that in the micturition phase. It is suggested that striatal dopamine may inhibit the micturition reflex via the dopamine D1 receptor-GABAergic direct striatal output pathway, and that disruption of this pathway may be what leads to bladder hyperactivity in patients with Parkinson's disease.

Lower urinary tract function in dementia of Lewy body type.

OBJECTIVE: Dementia of Lewy body (DLB) type is the second commonest degenerative cause of dementia and autonomic dysfunction has been recognised in DLB. Lower urinary tract (LUT) function in DLB has not been fully delineated. We investigated LUT function in DLB by evaluating clinical and urodynamic data. METHODS: We examined 11 patients (eight men, three women; age range 65-81; disease duration 2-14 years) with probable DLB. Urodynamic studies consisted of: measurement of postvoid residual in all patients, uroflowmetry in five, and electromyography (EMG) cystometry in seven. RESULTS: All patients had symptoms of LUT: urinary incontinence (urgency type/functional type due to dementia and immobility/both urgency and stress type in 7/2/1 patients, respectively); night-time frequency; urgency; and daytime frequency and voiding difficulty. Seven had postvoid residuals, and three had residual urine volume >100 ml. Decreased urinary flow was seen in all five and detrusor overactivity in 5/7 patients who underwent flowmetry and EMG cystometry, respectively. Low compliance detrusor (storage phase, n = 2; with bethanechol supersensitivity), an underactive detrusor (n = 4), an acontractile detrusor (n = 1), and detrusor-sphincter dyssynergia (voiding phase) (n = 1) were also seen; 2/3 patients who underwent motor unit potential analysis had neurogenic changes. CONCLUSION: LUT dysfunction is a common feature in DLB, not only due to dementia and immobility, but also to central and peripheral types of somato-autonomic dysfunction.