Hypothesis: Disrupted Regulation of the Intracranial Vascular and Cerebrospinal Fluid Circulations Causes Nocturia.

Nocturia is a prevalent condition and may result from nocturnal polyuria, whereby overnight urine production is excessive. Anecdotal cases of idiopathic nocturnal polyuria in which cerebrospinal fluid (CSF) disorders were identified suggest a potential mechanism. The skull constrains three circulatory systems: the CSF, interstitial fluid, and vascular supply. For each, fluid dynamics (pressure, volume, and flow) are closely regulated and adapt to changes such as recumbency and circadian variation. Pathologies disrupting this regulation, and thus impairing intracranial fluid dynamics, will place the brain environment at risk. Hence, compensatory responses are needed to maintain safe limits and prevent neurological deficits. We hypothesise that a change in the fluid dynamics for the intracranial CSF, interstitial, or vascular circulation means that positional or circadian changes during sleep trigger compensatory hormonal responses to protect the brain, but these also cause nocturnal polyuria. Natriuretic hormones are candidate mediators for protection against excess intracranial pressure or volume. PATIENT SUMMARY: A need to pass urine during the night, which is called nocturia, may be because of excessive overnight urine production. We propose that changes in fluid dynamics in the brain caused by lying down or daily body rhythms may trigger the release of hormones that could be a factor in nighttime urine production. This hypothesis should be explored in further investigations.

Assessment of patients with lower urinary tract symptoms where an undiagnosed neurological disease is suspected: A report from an International Continence Society consensus working group.

AIM: Lower urinary tract symptoms (LUTS) are a common urological referral, which sometimes can have a neurological basis in a patient with no formally diagnosed neurological disease ("occult neurology"). Early identification and specialist input is needed to avoid bad LUTS outcomes, and to initiate suitable neurological management. METHODS: The International Continence Society established a neurological working group to consider: Which neurological conditions may include LUTS as an early feature? What diagnostic evaluations should be undertaken in the LUTS clinic? A shortlist of conditions was drawn up by expert consensus and discussed at the annual congress of the International Neurourology Society. A multidisciplinary working group then generated recommendations for identifying clinical features and management. RESULTS: The relevant conditions are multiple sclerosis, multiple system atrophy, normal pressure hydrocephalus, early dementia, Parkinsonian syndromes (including early Parkinson's Disease and Multiple System Atrophy) and spinal cord disorders (including spina bifida occulta with tethered cord, and spinal stenosis). In LUTS clinics, the need is to identify additional atypical features; new onset severe LUTS (excluding infection), unusual aspects (eg, enuresis without chronic retention) or "suspicious" symptoms (eg, numbness, weakness, speech disturbance, gait disturbance, memory loss/cognitive impairment, and autonomic symptoms). Where occult neurology is suspected, healthcare professionals need to undertake early appropriate referral; central nervous system imaging booked from LUTS clinic is not recommended. CONCLUSIONS: Occult neurology is an uncommon underlying cause of LUTS, but it is essential to intervene promptly if suspected, and to establish suitable management pathways.

Cardiovascular autonomic responses in patients with Parkinson disease to pedunculopontine deep brain stimulation.

PURPOSE: Dysautonomia can be a debilitating feature of Parkinson disease (PD). Pedunculopontine nucleus (PPN) stimulation may improve gait disorders in PD, and may also result in changes in autonomic performance. METHODS: To determine whether pedunculopontine nucleus stimulation improves cardiovascular responses to autonomic challenges of postural tilt and Valsalva manoeuver, eight patients with pedunculopontine nucleus deep brain stimulation were recruited to the study; two were excluded for technical reasons during testing. Participants underwent head up tilt and Valsalva manoeuver with stimulation turned ON and OFF. Continuous blood pressure and ECG waveforms were recorded during these tests. In a single patient, local field potential activity was recorded from the implanted electrode during tilt. RESULTS: The fall in systolic blood pressure after tilt was significantly smaller with stimulation ON (mean - 8.3% versus - 17.2%, p = 0.044). Valsalva ratio increased with stimulation from median 1.15 OFF to 1.20 ON (p = 0.028). Baroreflex sensitivity increased during Valsalva compared to rest with stimulation ON versus OFF (p = 0.028). The increase in baroreflex sensitivity correlated significantly with the mean depth of PPN stimulating electrode contacts. This accounted for 89% of its variance (r = 0.943, p = 0.005). CONCLUSION: PPN stimulation can modulate the cardiovascular system in patients with PD. In this study, it reduced the postural fall in systolic blood pressure during head-up tilt and improved the cardiovascular response during Valsalva, presumably by altering the neural control of baroreflex activation.

Sensory thalamus and periaqueductal grey area local field potential signals during bladder filling.

The periaqueductal grey area and sensory thalamus are thought to be important nuclei involved in the supraspinal bladder control network. Deep brain stimulation of the periqueductal grey area has been shown to increase bladder capacity in the human. In a single patient, we have recorded local field potential signals from implanted deep brain stimulation electrodes within the sensory thalamus during filling cystometry with periaqueductal grey area deep brain stimulation in the ON and OFF states. In the OFF stimulation state, we demonstrate correlations between bladder volume and oscillations in the high gamma frequency band in the sensory thalamus. Stimulation of the periaqueductal grey area abolishes this correlated activity in the gamma frequency band and also suppresses oscillations within the sensory thalamus in the alpha frequency band. These findings support the involvement of the sensory thalamus in the afferent limb of bladder-related brain networks. They also suggest that periaqueductal grey area deep brain stimulation may disrupt the normal processing of afferent signals within the sensory thalamus which may be related to the effect of stimulation on bladder capacity.

Investigation of urinary storage symptoms in Parkinson's disease utilizing structural MRI techniques.

BACKGROUND: Lower urinary tract symptoms occur in 27% to 86% of patients with Parkinson's disease (PD), however, the mechanisms responsible for bladder dysfunction are not fully understood. This study utilized magnetic resonance imaging (MRI) to test the hypothesis that key brainstem bladder control areas (including the pontine micturition center and the pontine continence center (PCC) and their links with the basal ganglia are important in the development of urinary storage symptoms in PD. METHODS: Seventeen patients with PD completed a "bladder symptom questionnaire" and underwent diffusion-weighted MRI (1.5 T). Storage symptom severity and MRI measures of white matter microstructural integrity were correlated using tract-based spatial statistics. RESULTS: Mean diffusivity in the ventral brainstem correlated significantly with the bladder symptom severity in areas close to the predicted anatomical co-ordinates of the PCC. Tracts seeded from these regions passed via areas involved in pelvic floor musculature control and urinary voiding including the cerebellum, pallidum, and precentral gyrus. CONCLUSION: We used diffusion-weighted MRI to investigate the role of the brainstem and its structural connections in the development of urinary storage symptoms in PD. Our data suggest that the brainstem degenerative change in the vicinity of the PCC may be implicated in the pathogenesis of storage symptoms in these patients.

Beta oscillations and urinary voiding in Parkinson disease.

OBJECTIVES: To investigate the role of beta oscillations in urinary voiding and their association with lower urinary tract symptoms in Parkinson disease (PD). METHODS: We used surgically implanted deep brain stimulation electrodes to record local field potential signals from the subthalamic nucleus (STN) and globus pallidus interna (GPi) of patients with PD during urinary voiding. Five patients with STN electrodes and 5 patients with GPi electrodes were tested. We also explored correlations between beta oscillatory power and urinary symptoms assessed by the International Consultation on Incontinence Lower Urinary Tract Symptoms questionnaire. RESULTS: Beta suppression occurred during urinary voiding in the GPi (p < 0.05) but not the STN. Furthermore, the beta signal in the GPi during voiding correlated significantly with severity of incontinence and urinary frequency (p < 0.05). CONCLUSIONS: In this study, we have demonstrated that local field potentials can provide information about the neural control of the bladder. Our findings suggest that the GPi is implicated in the process of urinary voiding and that its mechanism of action is linked to signals in the beta frequency band. Moreover, our correlational analyses show that beta oscillations may be implicated more generally in the pathophysiology of lower urinary tract symptoms in PD.

Effects of pedunculopontine nucleus stimulation on human bladder function.

AIMS: The pedunculopontine nucleus (PPN) is a deep brain stimulation target for Parkinson's disease (PD). Unilateral PPN stimulation has been described in a previous case report to provoke urinary frequency, urgency and detrusor overactivity, due to probable activation of the pontine micturition center. Our aim was to evaluate the effect of bilateral PPN DBS on urodynamic parameters and to investigate the likely mechanisms using probabilistic tractography. METHODS: Six male PD subjects with bilateral PPN deep brain stimulators were recruited. Urodynamic bladder filling assessments were carried out with the stimulators ON and OFF. Two subjects also had diffusion-weighted and T1-weighted MRI scans performed and probabilistic tractography was carried out to describe white matter connections with the stimulated area. RESULTS: Five subjects completed urodynamic testing. PPN DBS did not give rise to detrusor overactivity or lower sensory thresholds during bladder filling. However, there was a significant increase in maximal bladder capacity with stimulation: mean bladder volume at maximal capacity was 199 mL (range 103-440) ON stimulation compared with 131 mL (range 39-230) OFF stimulation. Tractography demonstrated extensive connectivity to cortical and subcortical regions, some of which have been implicated in bladder control. Fiber pathways also passed close to the vicinity of the pontine micturition center. CONCLUSIONS: Bilateral PPN DBS did not have a detrimental effect on urodynamic filling parameters or produce detrusor overactivity, but did slightly increase maximal capacity. Possible mechanisms include long-range connectivity or local effects at the pontine micturition center.

State of the Art: Novel Applications for Deep Brain Stimulation.

OBJECTIVES: Deep brain stimulation (DBS) is a rapidly developing field of neurosurgery with potential therapeutic applications that are relevant to conditions traditionally viewed as beyond the limits of neurosurgery. Our objective, in this review, is to highlight some of the emerging applications of DBS within three distinct but overlapping spheres, namely trauma, neuropsychiatry, and autonomic physiology. REVIEW METHODS: An extensive literature review was carried out in MEDLINE, to identify relevant studies and review articles describing applications of DBS in the areas of trauma, neuropsychiatry and autonomic neuroscience. RESULTS: A wide range of applications of DBS in these spheres was identified, some having only been tested in one or two cases, others much better studied. CONCLUSIONS: We have identified various avenues for DBS to be applied for patient benefit in cases relevant to trauma, neuropsychiatry and autonomic neuroscience. Further developments in DBS technology and clinical trial design will enable these novel applications to be effectively and rigorously assessed and utilized most effectively.

Deep brain stimulation and multiple sclerosis: Therapeutic applications.

Deep brain stimulation is a neurosurgical technique that can be used to alleviate symptoms in a growing number of neurological conditions through modulating activity within brain networks. Certain applications of deep brain stimulation are relevant for the management of symptoms in multiple sclerosis. In this paper we discuss existing treatment options for tremor, facial pain and urinary dysfunction in multiple sclerosis and discuss evidence to support the potential use of deep brain stimulation for these symptoms.