Publications by authors named "Nicole C Keong"

12 Publications

  • Page 1 of 1

The splenial angle: a novel radiological index for idiopathic normal pressure hydrocephalus.

Eur Radiol 2021 May 15. Epub 2021 May 15.

Duke-NUS Medical School, Singapore, Singapore.

Objectives: To evaluate the utility of the splenial angle (SA), an axial angular index of lateral ventriculomegaly measured on diffusion tensor MRI color fractional anisotropy maps, in differentiating NPH from Alzheimer's disease (AD), Parkinson's disease (PD), and healthy controls (HC), and post-shunt changes in NPH, compared to Evans' index and callosal angle.

Methods: Evans' index, callosal angle, and SA were measured on brain MRI of 76 subjects comprising equal numbers of age- and sex-matched subjects from each cohort of NPH, AD, PD, and HC by two raters. Receiver operating characteristics (ROC) and multivariable analysis were used to assess the screening performance of each measure in differentiating and predicting NPH from non-NPH groups respectively. Temporal changes in the measures on 1-year follow-up MRI in 11 NPH patients (with or without ventriculoperitoneal shunting) were also assessed.

Results: Inter-rater and intra-rater reliability were excellent for all measurements (intraclass correlation coefficients > 0.9). Pairwise comparison showed that SA was statistically different between NPH and AD/PD/HC subjects (p < 0.0001). SA performed the best in predicting NPH, with an area under the ROC curve of > 0.98, and was the only measure left in the final model of the multivariable analysis. Significant (p < 0.01) change in SA was seen at follow-up MRI of NPH patients who were shunted compared to those who were not.

Conclusions: The SA is readily measured on axial DTI color FA maps compared to the callosal angle and shows superior performance differentiating NPH from neurodegenerative disorders and sensitivity to ventricular changes in NPH after surgical intervention.

Key Points: • The splenial angle is a novel simple angular radiological index proposed for idiopathic normal pressure hydrocephalus, measured in the ubiquitous axial plane on DTI color fractional anisotropy maps. • The splenial angle quantitates the compression and stretching of the posterior callosal commissural fibers alongside the distended lateral ventricles in idiopathic normal pressure hydrocephalus (NPH) using tools readily accessible in clinical practice and shows excellent test-retest reliability. • Splenial angle outperforms Evans' index and callosal angle in predicting NPH from healthy, Parkinson's disease, and Alzheimer's disease subjects on ROC analysis with an area under the curve of > 0.98 and is sensitive to morphological ventricular changes in NPH patients after ventricular shunting.
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http://dx.doi.org/10.1007/s00330-021-07871-4DOI Listing
May 2021

Single Center Experience in Cerebrospinal Fluid Dynamics Testing.

Acta Neurochir Suppl 2021 ;131:311-313

Division of Neurosurgery, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.

Normal pressure hydrocephalus is more complex than a simple disturbance of the cerebrospinal fluid (CSF) circulation. Nevertheless, an assessment of CSF dynamics is key to making decisions about shunt insertion, shunt malfunction, and for further management if a patient fails to improve. We summarize our 25 years of single center experience in CSF dynamics assessment using pressure measurement and analysis. 4473 computerized infusion tests have been performed. We have shown that CSF infusion studies are safe, with incidence of infection at less than 1%. Raised resistance to CSF outflow positively correlates (p < 0.014) with improvement after shunting and is associated with disturbance of cerebral blood flow and its autoregulation (p < 0.02). CSF infusion studies are valuable in assessing possible shunt malfunction in vivo and for avoiding unnecessary revisions. Infusion tests are safe and provide useful information for clinical decision-making for the management of patients suffering from hydrocephalus.
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http://dx.doi.org/10.1007/978-3-030-59436-7_58DOI Listing
June 2021

Lower Breakpoint of Intracranial Amplitude-Pressure Relationship in Normal Pressure Hydrocephalus.

Acta Neurochir Suppl 2021 ;131:307-309

Academic Neurosurgery, Cambridge University Hospital, Cambridge, UK.

The relationship between intracranial pulse amplitude (AMP) and mean intracranial pressure (ICP) has been previously described. Generally, AMP increases proportionally to rises in ICP. However, at low ICP a lower breakpoint (LB) of amplitude-pressure relationship can be observed, below which pulse amplitude stays constant when ICP varies. Theoretically, below this breakpoint, the pressure-volume relationship is linear (good compensatory reserve, brain compliance stays constant); above the breakpoint, it is exponential (brain compliance decreases with rising ICP).Infusion tests performed in 169 patients diagnosed for idiopathic normal pressure hydrocephalus (iNPH) during the period 2004-2013 were available for analysis. A lower breakpoint was observed in 62 patients diagnosed for iNPH. Improvement after shunt surgery in patients in whom LB was recorded was 77% versus 90% in patients where LB was absent (p < 0.02). There was no correlation between improvement and slope of amplitude-pressure line above LB.The detection of a lower breakpoint is associated with less frequent improvement after shunting in NPH. It may be interpreted that cerebrospinal fluid dynamics of patients working on the flat part of the pressure-volume curve and having a 'luxurious' compensatory reserve, are more frequently caused by brain atrophy, which is obviously not responding to shunting.
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http://dx.doi.org/10.1007/978-3-030-59436-7_57DOI Listing
June 2021

Liminal spaces in neurosurgery - tensions between expectations of the patient and their surgeon at the threshold of informed consent.

Authors:
Nicole C Keong

Br J Neurosurg 2021 Jan 19:1-7. Epub 2021 Jan 19.

Department of Neurosurgery, National Neuroscience Institute, Singapore, Singapore.

The concept of 'liminality', describing the universal human experience of transition in status, has been shown to be relevant in addressing the provision of healthcare needs within clinical medicine. Consent may be viewed as a threshold which patients must cross between a state of integration of information to a state of transformation into knowledge. This article reframes gaps in the modern surgical approach to the process of 'informed consent' via the lens of liminality, drawing on key illustrative cases from the medicolegal evolution in the UK and Commonwealth. A focused literature search was performed for informative medical legal cases addressing or contributing to the understanding of "informed consent". Searches and references to sources of case law were performed using Westlaw and Hein Online databases. Searches for secondary sources for interpretation and discussions of case law and concepts, as well as topics of liminality and autonomy, were performed via PubMed and Academia databases and relevant online resources. The paper organizes the illustrative material using the following approach:- a discussion and dissection of the i) evolution of consent as a duty to warn, comprising a summary of landmark cases, ii) materiality of risks and what a particular patient would wish to know and iii) conceptual relevance of troublesome knowledge, relational autonomy and threshold concepts in learning to key examples in case law and the process of informed consent. Modern surgical practice of informed consent must strive for clarity of mutual understanding. The framework of liminality allows us to understand the in-between states encountered during the patient's journey. An ability to recognize such gaps in expectations, and develop tools to promote transformational learning, would allow the surgeon to evolve from prudent practitioner to patient mentor at the threshold of informed consent.
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http://dx.doi.org/10.1080/02688697.2021.1872775DOI Listing
January 2021

The National Neuroscience Institute External Ventricular Drain Study: A Pragmatic Multisite Risk-Stratification Pathway to Reduce Ventriculostomy-Related Infection.

World Neurosurg 2020 Mar 19;135:e126-e136. Epub 2019 Nov 19.

Department of Neurosurgery, National Neuroscience Institute, Singapore, Singapore; Duke-NUS Medical School, Singapore, Singapore. Electronic address:

Objective: Ventriculostomy-related infection (VRI) is associated with potential serious morbidity, extended hospitalization duration, increased health care costs, and mortality. We assessed the effectiveness of a pragmatic risk-stratification pathway for external ventricular drain (EVD) management, allowing for surgical decision making, in reducing the rate of VRIs.

Methods: Two studies were performed concurrently. A retrospective audit of EVD infection rates and outcomes in our unit across 3 hospitals was conducted from January to December 2014. The second prospective study compared the same variables during the implementation of the EVD pathway across the 3 sites from January 2015 to December 2016.

Results: The number of patients requiring EVDs increased from 2014 to 2016 (165 vs. 189 vs. 197 patients, respectively), with a significant increase in patients with intraventricular hemorrhage (P = 0.009). Despite increasing risk, overall EVD infections decreased during the implementation period, from 4.8% (8/165) in 2014 to 3.7% in 2015 (7/189) and 2.0% in 2016 (4/197, P = 0.33). In 2 sites (site 1, 2.0% vs. 2.1% vs. 1.9%, and site 2, 4.7% vs. 5.0% vs. 5.3%), transition to the EVD risk-stratification pathway maintained already low infection rates; in site 3, EVD infections decreased from 6.8% (5/73) to 3.9% (4/102) and 0% (0/86, P = 0.06).

Conclusions: The introduction of a pragmatic evidence-based risk-stratification pathway, in which different options for EVD management are incorporated, results in low EVD infection rates across a multisite institutional practice. Our results are comparable to published protocols involving the implementation of standard care bundles and/or antibacterial EVDs alone, in reducing VRIs.
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http://dx.doi.org/10.1016/j.wneu.2019.11.070DOI Listing
March 2020

DTI Profiles for Rapid Description of Cohorts at the Clinical-Research Interface.

Front Med (Lausanne) 2018 10;5:357. Epub 2019 Jan 10.

Department of Neurosurgery, National Neuroscience Institute, Singapore, Singapore.

Normal pressure hydrocephalus (NPH) is a syndrome comprising gait disturbance, cognitive decline and urinary incontinence that is an unique model of reversible brain injury, but it presents as a challenging spectrum of disease cohorts. Diffusion Tensor Imaging (DTI), with its ability to interrogate structural white matter patterns at a microarchitectural level, is a potentially useful tool for the confirmation and characterization of disease cohorts at the clinical-research interface. However, obstacles to its widespread use involve the need for consistent DTI analysis and interpretation tools across collaborator sites. We present the use of DTI profiles, a simplistic methodology to interpret white matter injury patterns based on the morphology of diffusivity parameters. We examined 13 patients with complex NPH, i.e., patients with NPH and overlay from multiple comorbidities, including vascular risk burden and neurodegenerative disease, undergoing extended CSF drainage, clinical assessments, and multi-modal MR imaging. Following appropriate exclusions, we compared the morphology of DTI profiles in such complex NPH patients ( = 12, comprising 4 responders and 8 non-responders) to exemplar DTI profiles from a cohort of classic NPH patients ( = 16) demonstrating responsiveness of white matter injury to ventriculo-peritoneal shunting. In the cohort of complex NPH patients, mean age was 71.3 ± 7.6 years (10 males, 2 females) with a mean MMSE score of 21.1. There were 5 age-matched healthy controls, mean age was 73.4 ± 7.2 years (1 male, 4 females) and mean MMSE score was 26.8. In the exemplar cohort of classic NPH patients, mean age was 74.7 ± 5.9 years (10 males, 6 females) and mean MMSE score was 24.1. There were 9 age-matched healthy controls, mean age was 69.4 ± 9.7 years (4 males, 5 females) and mean MMSE score was 28.6. We found that, despite the challenges of acquiring DTI metrics from differing scanners across collaborator sites and NPH patients presenting as differing cohorts along the spectrum of disease, DTI profiles for responsiveness to interventions were comparable. Distinct DTI characteristics were demonstrated for complex NPH responders vs. non-responders. The morphology of DTI profiles for complex NPH responders mimicked DTI patterns found in predominantly shunt-responsive patients undergoing intervention for classic NPH. However, DTI profiles for complex NPH non-responders was suggestive of atrophy. Our findings suggest that it is possible to use DTI profiles to provide a methodology for rapid description of differing cohorts of disease at the clinical-research interface. By describing DTI measures morphologically, it was possible to consistently compare white matter injury patterns across international collaborator datasets.
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http://dx.doi.org/10.3389/fmed.2018.00357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6335243PMC
January 2019

Structural correlates of cognitive impairment in normal pressure hydrocephalus.

Acta Neurol Scand 2019 Mar 3;139(3):305-312. Epub 2018 Dec 3.

Department of Psychiatry, University of Cambridge, Cambridge, UK.

Objectives: The pathological bases for the cognitive and neuropsychiatric symptoms in normal pressure hydrocephalus (NPH) have not been elucidated. However, the symptoms may indicate dysfunction of subcortical regions. Previously, volume reductions of subcortical deep grey matter (SDGM) structures have been observed in NPH patients. The present study used automated segmentation methods to investigate whether SDGM structure volumes are associated with cognitive and neuropsychiatric measures.

Methods: Fourteen NPH patients and eight healthy controls were included in the study. Patients completed neuropsychological tests of general cognition, verbal learning and memory, verbal fluency and measures of apathy and depression pre- and postshunt surgery. Additionally, patients underwent 3 Tesla T1-weighted magnetic resonance imaging at baseline and 6 months postoperatively. Controls were scanned once. SDGM structure volumes were estimated using automated segmentation (FSL FIRST). Since displacement of the caudate nuclei occurred for some patients due to ventriculomegaly, patient caudate volumes were also estimated using manual tracing. Group differences in SDGM structure volumes were investigated, as well as associations between volumes and cognitive and neuropsychiatric measures in patients.

Results: Volumes of the caudate, thalamus, putamen, pallidum, hippocampus and nucleus accumbens (NAcc) were significantly reduced in the NPH patients compared to controls. In the NPH group, smaller caudate and NAcc volumes were associated with poorer performance on neuropsychological tests and increased severity of neuropsychiatric symptoms, while reduced volume of the pallidum was associated with better performance on the MMSE and reduced apathy.

Conclusions: Striatal volume loss appears to be associated with cognitive and neuropsychiatric changes in NPH.
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http://dx.doi.org/10.1111/ane.13052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6492129PMC
March 2019

Cerebral autoregulation, cerebrospinal fluid outflow resistance, and outcome following cerebrospinal fluid diversion in normal pressure hydrocephalus.

J Neurosurg 2018 03;130(1):154-162

1Division of Neurosurgery, University of Cambridge Department of Clinical Neuroscience, Addenbrooke's Hospital, Cambridge, United Kingdom; and.

Objective: Normal pressure hydrocephalus is not simply the result of a disturbance in CSF circulation, but often includes cardiovascular comorbidity and abnormalities within the cerebral mantle. In this study, the authors have examined the relationship between the global autoregulation pressure reactivity index (PRx), the profile of disturbed CSF circulation and pressure-volume compensation, and their possible effects on outcome after surgery.

Methods: The authors studied a cohort of 131 patients in whom a clinical suspicion of normal pressure hydrocephalus was investigated. Parameters describing CSF compensation and circulation were calculated during the CSF infusion test, and PRx was calculated from CSF pressure and mean arterial blood pressure (MAP) recordings. A simple scale was used to mark the patients’ outcome 6 months after surgery (improvement, temporary improvement, and no improvement).

Results: The PRx was negatively correlated with resistance to CSF outflow (R = -0.18; p = 0.044); patients with normal CSF circulation tended to have worse autoregulation. The correlation for patients who were surgically treated (n = 83) was R = -0.28; p = 0.01, and it was stronger in patients who experienced sustained improvement after surgery (n = 48, R = -0.43; p = 0.002). In patients who did not improve, the correlation was not significantly different from zero (n = 19, R = -0.07; p = 0.97). There was a trend toward higher values for PRx in nonresponders than in responders (0.16 ± 0.04 vs 0.09 ± 0.02, respectively; p = 0.061), associated with higher MAP values (107.2 ± 8.2 in nonresponders vs 89.5 ± 3.5 in responders; p = 0.195). The product of MAP × (1 + PRx), which was proposed as a measure of combined arterial hypertension and deranged autoregulation, showed a significant association with outcome (greater value in nonresponders; p = 0.013).

Conclusion: Autoregulation proves to associate with CSF circulation and appears strongest in shunt responders. Outcome following CSF diversion is possibly most favorable when CSF outflow resistance is increased and global cerebral autoregulation is intact, in combination with arterial normotension.
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http://dx.doi.org/10.3171/2017.7.JNS17216DOI Listing
March 2018

Is There a Link Between ICP-Derived Infusion Test Parameters and Outcome After Shunting in Normal Pressure Hydrocephalus?

Acta Neurochir Suppl 2018 ;126:229-232

Division of Neurosurgery, Cambridge University Hospital, Cambridge, UK.

Objective: The term "hydrocephalus" encompasses a range of disorders characterised by clinical symptoms, abnormal brain imaging and derangement of cerebrospinal fluid (CSF) dynamics. The ability to elucidate which patients would benefit from CSF diversion (a shunt or third ventriculostomy) is often unclear. Similar difficulties are encountered in shunted patients to predict the scope for improvement by shunt re-adjustment or revision.

Materials And Methods: We compared retrospective pre-shunting infusion test results performed in 310 adult patients diagnosed with normal pressure hydrocephalus (NPH) and their improvement after shunting.

Results: Resistance to CSF outflow correlated significantly with improvement (p < 0.05). Other markers known from the literature, such as amplitude in CSF pulse pressure, the slope of the amplitude-pressure regression line, or elasticity did not show any correlation with outcome.

Conclusion: Outcome following shunting in adult NPH is associated with resistance to CSF outflow; however, the latter cannot be taken as an absolute predictor of shunt response.
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http://dx.doi.org/10.1007/978-3-319-65798-1_46DOI Listing
July 2018

Diffusion tensor imaging profiles reveal specific neural tract distortion in normal pressure hydrocephalus.

PLoS One 2017 17;12(8):e0181624. Epub 2017 Aug 17.

Neurosurgical Division, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.

Background: The pathogenesis of normal pressure hydrocephalus (NPH) remains unclear which limits both early diagnosis and prognostication. The responsiveness to intervention of differing, complex and concurrent injury patterns on imaging have not been well-characterized. We used diffusion tensor imaging (DTI) to explore the topography and reversibility of white matter injury in NPH pre- and early after shunting.

Methods: Twenty-five participants (sixteen NPH patients and nine healthy controls) underwent DTI, pre-operatively and at two weeks post-intervention in patients. We interrogated 40 datasets to generate a full panel of DTI measures and corroborated findings with plots of isotropy (p) vs. anisotropy (q).

Results: Concurrent examination of DTI measures revealed distinct profiles for NPH patients vs. controls. PQ plots demonstrated that patterns of injury occupied discrete white matter districts. DTI profiles for different white matter tracts showed changes consistent with i) predominant transependymal diffusion with stretch/ compression, ii) oedema with or without stretch/ compression and iii) predominant stretch/ compression. Findings were specific to individual tracts and dependent upon their proximity to the ventricles. At two weeks post-intervention, there was a 6·7% drop in axial diffusivity (p = 0·022) in the posterior limb of the internal capsule, compatible with improvement in stretch/ compression, that preceded any discernible changes in clinical outcome. On PQ plots, the trajectories of the posterior limb of the internal capsule and inferior longitudinal fasciculus suggested attempted 'round trips'. i.e. return to normality.

Conclusion: DTI profiling with p:q correlation may offer a non-invasive biomarker of the characteristics of potentially reversible white matter injury.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0181624PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5560677PMC
October 2017

Imaging normal pressure hydrocephalus: theories, techniques, and challenges.

Neurosurg Focus 2016 Sep;41(3):E11

Neurosurgical Division, Department of Clinical Neurosciences, University of Cambridge, United Kingdom; and.

The pathophysiology of NPH continues to provoke debate. Although guidelines and best-practice recommendations are well established, there remains a lack of consensus about the role of individual imaging modalities in characterizing specific features of the condition and predicting the success of CSF shunting. Variability of clinical presentation and imperfect responsiveness to shunting are obstacles to the application of novel imaging techniques. Few studies have sought to interpret imaging findings in the context of theories of NPH pathogenesis. In this paper, the authors discuss the major streams of thought for the evolution of NPH and the relevance of key imaging studies contributing to the understanding of the pathophysiology of this complex condition.
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http://dx.doi.org/10.3171/2016.7.FOCUS16194DOI Listing
September 2016

Apathy, ventriculomegaly and neurocognitive improvement following shunt surgery in normal pressure hydrocephalus.

Br J Neurosurg 2016 12;30(1):38-42. Epub 2015 May 12.

a Department of Psychiatry , University of Cambridge, Addenbrooke's Hospital , Cambridge , UK.

Introduction: Apathy - impaired motivation and goal-directed behaviour - is a common yet often overlooked symptom in normal pressure hydrocephalus (NPH). Caudate atrophy often yields apathetic symptoms; however, this structural and functional relationship has not yet been explored in NPH. Additionally, little is known about the relationship between apathy and post-shunt cognitive recovery.

Methods: This audit investigated whether apathetic symptoms improve following shunt surgery in NPH, and whether this relates to cognitive response. In addition, we assessed the relationship between ventriculomegaly and apathy using the bicaudate ratio. Twenty-two patients with NPH completed the Mini-Mental State Examination (MMSE), the Apathy Evaluation Scale (AES) and the Geriatric Depression Scale (GDS) before and 3-9 months after shunt surgery. Pre-operative ventriculomegaly was correlated with pre-operative AES and GDS scores. Difference scores (post-shunt minus baseline values) for AES and GDS were correlated with cognitive outcome.

Results: Greater pre-operative ventriculomegaly was associated with increased level of apathy and depression. A reduction in apathetic symptoms following shunt surgery was associated with improved performance on the MMSE.

Conclusions: Apathy may be indicative of a greater degree of subcortical atrophy in NPH and may relate to functional outcome.
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http://dx.doi.org/10.3109/02688697.2015.1029429DOI Listing
January 2017
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