Cauda equina syndrome.

Aims: Patients with cauda equina syndrome (CES) require emergency imaging and surgical decompression. The severity and type of symptoms may influence the timing of imaging and surgery, and help predict the patient's prognosis. Categories of CES attempt to group patients for management and prognostication purposes. We aimed in this study to assess the inter-rater reliability of dividing patients with CES into categories to assess whether they can be reliably applied in clinical practice and in research. Methods: A literature review was undertaken to identify published descriptions of categories of CES. A total of 100 real anonymized clinical vignettes of patients diagnosed with CES from the Understanding Cauda Equina Syndrome (UCES) study were reviewed by consultant spinal surgeons, neurosurgical registrars, and medical students. All were provided with published category definitions and asked to decide whether each patient had 'suspected CES'; 'early CES'; 'incomplete CES'; or 'CES with urinary retention'. Inter-rater agreement was assessed for all categories, for all raters, and for each group of raters using Fleiss's kappa. Results: Each of the 100 participants were rated by four medical students, five neurosurgical registrars, and four consultant spinal surgeons. No groups achieved reasonable inter-rater agreement for any of the categories. CES with retention versus all other categories had the highest inter-rater agreement (kappa 0.34 (95% confidence interval 0.27 to 0.31); minimal agreement). There was no improvement in inter-rater agreement with clinical experience. Across all categories, registrars agreed with each other most often (kappa 0.41), followed by medical students (kappa 0.39). Consultant spinal surgeons had the lowest inter-rater agreement (kappa 0.17). Conclusion: Inter-rater agreement for categorizing CES is low among clinicians who regularly manage these patients. CES categories should be used with caution in clinical practice and research studies, as groups may be heterogenous and not comparable.

Oral microbes and the formation of cerebral abscesses: A single-centre retrospective study.

OBJECTIVE: Intracranial abscesses are relatively uncommon, but can result in significant mortality and morbidity. Whilst many potential causes of brain abscesses are recognised, in many cases the origin of infection remains clinically unidentified. Our objective was to investigate the role of bacteria found in the oral cavity in the development of brain abscesses. METHODS: A retrospective analysis was performed using data from 87 patients admitted to a single UK neurosurgical unit with brain abscesses over a 16-year period. Using microbiological data obtained from abscess sampling and peripheral cultures, species of bacteria were categorised in patients where no primary source of infection was identified (NSI) for their brain abscess (n = 52), or where an infective source (ISI) was identified. The microbiological data was then screened to identify common oral bacteria in each group. RESULTS: Brain abscesses from the ISI group (n = 35) demonstrated a significantly lower preponderance of oral bacteria (n = 8), than the NSI group (n = 29) (p < 0.05). Brain abscesses from the NSI group also had significantly higher counts of Streptococcus anginosus compared to ISI (p < 0.05), with brain abscesses being most common in the frontal and parietal lobes for both ISI and NSI. CONCLUSIONS: These findings suggest that the oral cavity could be considered as a source of occult infection in cases of brain abscess where no clear cause has been identified. Future studies should include oral screening and microbiome analysis to better understand the mechanisms involved and develop approaches for prevention. CLINICAL SIGNIFICANCE STATEMENT: Oral bacteria may be an under-recognised cause of brain abscesses. Careful review of oral health in brain abscess patients may help establish causation, particularly in patients with no cause for their abscess identified. Good levels of oral health may help prevent the development of brain abscesses in some individuals.

Presentation, management, and outcomes of cauda equina syndrome up to one year after surgery, using clinician and participant reporting: A multi-centre prospective cohort study.

Background: Cauda equina syndrome (CES) results from nerve root compression in the lumbosacral spine, usually due to a prolapsed intervertebral disc. Evidence for management of CES is limited by its infrequent occurrence and lack of standardised clinical definitions and outcome measures. Methods: This is a prospective multi-centre observational cohort study of adults with CES in the UK. We assessed presentation, investigation, management, and all Core Outcome Set domains up to one year post-operatively using clinician and participant reporting. Univariable and multivariable associations with the Oswestry Disability Index (ODI) and urinary outcomes were investigated. Findings: In 621 participants with CES, catheterisation for urinary retention was required pre-operatively in 31% (191/615). At discharge, only 13% (78/616) required a catheter. Median time to surgery from symptom onset was 3 days (IQR:1-8) with 32% (175/545) undergoing surgery within 48 h. Earlier surgery was associated with catheterisation (OR:2.2, 95%CI:1.5-3.3) but not with admission ODI or radiological compression. In multivariable analyses catheter requirement at discharge was associated with pre-operative catheterisation (OR:10.6, 95%CI:5.8-20.4) and one-year ODI was associated with presentation ODI (r = 0.3, 95%CI:0.2-0.4), but neither outcome was associated with time to surgery or radiological compression. Additional healthcare services were required by 65% (320/490) during one year follow up. Interpretation: Post-operative functional improvement occurred even in those presenting with urinary retention. There was no association between outcomes and time to surgery in this observational study. Significant healthcare needs remained post-operatively. Funding: DCN Endowment Fund funded study administration. Castor EDC provided database use. No other study funding was received.

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.

The Central Autonomic Network and Regulation of Bladder Function.

The autonomic nervous system (ANS) is involved in the regulation of physiologic and homeostatic parameters relating particularly to the visceral organs and the co-ordination of physiological responses to threat. Blood pressure and heart rate, respiration, pupillomotor reactivity, sexual function, gastrointestinal secretions and motility, and urine storage and micturition are all under a degree of ANS control. Furthermore, there is close integration between the ANS and other neural functions such as emotion and cognition, and thus brain regions that are known to be important for autonomic control are also implicated in emotional functions. In this review we explore the role of the central ANS in the control of the bladder, and the implications of this for bladder dysfunction in diseases of the ANS.

The pedunculopontine region and breathing in Parkinson's disease.

OBJECTIVE: Respiratory abnormalities such as upper airway obstruction are common in Parkinson's disease (PD) and are an important cause of mortality and morbidity. We tested the effect of pedunculopontine region (PPNr) stimulation on respiratory maneuvers in human participants with PD, and separately recorded PPNr neural activity reflected in the local field potential (LFP) during these maneuvers. METHODS: Nine patients with deep brain stimulation electrodes in PPNr, and seven in globus pallidus interna (GPi) were studied during trials of maximal inspiration followed by forced expiration with stimulation OFF and ON. Local field potentials (LFPs) were recorded in the unstimulated condition. RESULTS: PEFR increased from 6.41 ± 0.63 L/sec in the OFF stimulation state to 7.5 L ± 0.65 L/sec in the ON stimulation state (z = -2.666, df = 8, P = 0.024). Percentage improvement in PEFR was strongly correlated with proximity of the stimulated electrode contact to the mesencephalic locomotor region in the rostral PPN (r = 0.814, n = 9, P = 0.008). Mean PPNr LFP power increased within the alpha band (7-11 Hz) during forced respiratory maneuvers (1.63 ± 0.16 µV2/Hz) compared to resting breathing (0.77 ± 0.16 µV2/Hz; z = -2.197, df = 6, P = 0.028). No changes in alpha activity or spirometric indices were seen with GPi recording or stimulation. Percentage improvement in PEFR was strongly positively correlated with increase in alpha power (r = 0.653, n = 14 (7 PPNr patients recorded bilaterally), P = 0.0096). INTERPRETATION: PPNr stimulation in PD improves indices of upper airway function. Increased alpha-band activity is seen within the PPNr during forced respiratory maneuvers. Our findings suggest a link between the PPNr and respiratory performance in PD.

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.

Understanding cauda equina syndrome: protocol for a UK multicentre prospective observational cohort study.

INTRODUCTION: Cauda equina syndrome (CES) is a potentially devastating condition caused by compression of the cauda equina nerve roots. This can result in bowel, bladder and sexual dysfunction plus lower limb weakness, numbness and pain. CES occurs infrequently, but has serious potential morbidity and medicolegal consequences. This study aims to identify and describe the presentation and management of patients with CES in the UK. METHODS AND ANALYSIS: Understanding Cauda Equina Syndrome (UCES) is a prospective and collaborative multicentre cohort study of adult patients with confirmed CES managed at specialist spinal centres in the UK. Participants will be identified using neurosurgical and orthopaedic trainee networks to screen referrals to spinal centres. Details of presentation, investigations, management and service usage will be recorded. Both patient-reported and clinician-reported outcome measures will be assessed for 1 year after surgery. This will establish the incidence of CES, current investigation and management practices, and adherence to national standards of care. Outcomes will be stratified by clinical presentation and patient management. Accurate and up to date information about the presentation, management and outcome of patients with CES will inform standards of service design and delivery for this important but infrequent condition. ETHICS AND DISSEMINATION: UCES received a favourable ethical opinion from the South East Scotland Research Ethics Committee 02 (Reference: 18/SS/0047; IRAS ID: 233515). All spinal centres managing patients with CES in the UK will be encouraged to participate in UCES. Study results will be published in medical journals and shared with local participating sites. TRIAL REGISTRATION NUMBER: ISRCTN16828522; Pre-results.

Neuromodulation for Pelvic and Urogenital Pain.

Chronic pain affecting the pelvic and urogenital area is a major clinical problem with heterogeneous etiology, affecting both male and female patients and severely compromising quality of life. In cases where pharmacotherapy is ineffective, neuromodulation is proving to be a potential avenue to enhance analgesic outcomes. However, clinicians who frequently see patients with pelvic pain are not traditionally trained in a range of neuromodulation techniques. The aim of this overview is to describe major types of pelvic and urogenital pain syndromes and the neuromodulation approaches that have been trialed, including peripheral nerve stimulation, dorsal root ganglion stimulation, spinal cord stimulation, and brain stimulation techniques. Our conclusion is that neuromodulation, particularly of the peripheral nerves, may provide benefits for patients with pelvic pain. However, larger prospective randomized studies with carefully selected patient groups are required to establish efficacy and determine which patients are likely to achieve the best outcomes.

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.