47 results on '"Jalloh, I"'
Search Results
2. The hidden risks of hearing tests and programmable ventriculoperitoneal shunt valves.
- Author
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Foster-Davies, L. A., Naushahi, M. J., Smart, H., and Jalloh, I
- Subjects
AUDIOMETRY ,CEREBROSPINAL fluid shunts ,RELIEF valves ,MAGNETIC flux density ,VALVES ,CONDUCTIVE hearing loss - Abstract
Programmable variable pressure valves were introduced in the 1980s, providing a non-invasive solution to post-operative alterations of the valve opening pressure to address problems of under or overdrainage. Since their increased use in the treatment of hydrocephalus, there have been case reports of unintentional alterations of the valve opening pressure following exposure to magnetic fields in everyday environments, from televisions to rollercoasters. Here we describe two cases of patients' programmable valves being altered following audiology assessments. We subsequently discuss some of the available research on the safety of these valves in various magnetic field strengths, alongside interim and updated recommendations made by the British Society of Audiologists with regards to testing of children with programmable shunts in place. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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3. Preoperative smoking cessation: a questionnaire study
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Owen, D., Bicknell, C., Hilton, C., Lind, J., Jalloh, I., Owen, M., and Harrison, R.
- Published
- 2007
4. Two-dimensional DCT/IDCT architecture.
- Author
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Aggoun, A. and Jalloh, I.
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- *
COMPUTER architecture , *ALGORITHMS - Abstract
Presents a fully parallel architecture for the computation of a two-dimensional discrete cosine transform (DCT), based on row-column decomposition. Use of the same one-dimensional DCT unit for the row and column computations and (N[sup 2] + N) registers to perform the transposition; Regularity and modularity of the architecture; Reduction of the number of accumulators from N to one.
- Published
- 2003
- Full Text
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5. The Intrathecal Baclofen Withdrawal Syndrome: A Systematic Review
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Muirhead, W.R., Baylem, N., Jalloh, I., and Vloeberghs, M.
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- 2010
- Full Text
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6. An unusual case of haemorrhagic stroke.
- Author
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Marcus H, Jalloh I, Roberts R, and Martin P
- Published
- 2009
7. Characterizing Diffusion from Microdialysis Catheters in the Human Brain: A Magnetic Resonance Imaging Study With Gadobutrol.
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Stovell MG, Ruetten PPR, Tozer DJ, Launey Y, Zimphango C, Thelin EP, Lupson VC, Giorgi-Coll S, Carpenter TA, Mada MO, Jalloh I, Helmy A, Wilson MH, Graves MJ, Menon DK, Carpenter KLH, and Hutchinson PJ
- Subjects
- Humans, Male, Adult, Female, Middle Aged, Brain metabolism, Brain diagnostic imaging, Young Adult, Diffusion, Contrast Media, Catheters, Microdialysis methods, Microdialysis instrumentation, Magnetic Resonance Imaging methods, Brain Injuries, Traumatic metabolism, Brain Injuries, Traumatic diagnostic imaging, Organometallic Compounds
- Abstract
Cerebral microdialysis (CMD) catheters allow continuous monitoring of patients' cerebral metabolism in severe traumatic brain injury (TBI). The catheters consist of a terminal semi-permeable membrane that is inserted into the brain's interstitium to allow perfusion fluid to equalize with the surrounding cerebral extracellular environment before being recovered through a central non-porous channel. However, it is unclear how far recovered fluid and suspended metabolites have diffused from within the brain, and therefore what volume or region of brain tissue the analyses of metabolism represent. We assessed diffusion of the small magnetic resonance (MR)-detectible molecule gadobutrol from microdialysis catheters in six subjects (complete data five subjects, incomplete data one subject) who had sustained a severe TBI. Diffusion pattern and distance in cerebral white matter were assessed using T
1 (time for MR spin-lattice relaxation) maps at 1 mm isotropic resolution in a 3 Tesla MR scanner. Gadobutrol at 10 mmol/L diffused from cerebral microdialysis catheters in a uniform spheroidal (ellipsoid of revolution) pattern around the catheters' semipermeable membranes, and across gray matter-white matter boundaries. Evidence of gadobutrol diffusion was found up to a mean of 13.4 ± 0.5 mm (mean ± standard deviation [SD]) from catheters, but with a steep concentration drop off so that ≤50% of maximum concentration was achieved at ∼4 mm, and ≤10% of maximum was found beyond ∼7 mm from the catheters. There was little variation between subjects. The relaxivity of gadobutrol in human cerebral white matter was estimated to be 1.61 ± 0.38 L.mmol-1 sec-1 (mean ± SD); assuming gadobutrol remained extracellular thereby occupying 20% of total tissue volume (interstitium), and concentration equilibrium with perfusion fluid was achieved immediately adjacent to catheters after 24 h of perfusion. No statistically significant change was found in the concentration of the extracellular metabolites glucose, lactate, pyruvate, nor the lactate/pyruvate ratio during gadobutrol perfusion when compared with period of baseline microdialysis perfusion. Cerebral microdialysis allows continuous monitoring of regional cerebral metabolism-the volume of which is now clearer from this study. It also has the potential to deliver small molecule therapies to focal pathologies of the human brain. This study provides a platform for future development of new catheters optimally designed to treat such conditions.- Published
- 2024
- Full Text
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8. Measurement of Head Circumference Using a Smartphone: Feasibility Cohort Study.
- Author
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Yordanov S, Akhter K, Quan Teh J, Naushahi J, and Jalloh I
- Abstract
Background: Accurate head circumference (HC) measurement is essential when assessing neonates and infants. Tape measure HC measurements are prone to errors, particularly when performed by parents/guardians, due to individual differences in head shape, hair style and texture, subject cooperation, and examiner techniques, including tape measure placement and tautness. There is, therefore, the need for a more reliable method., Objective: The primary objective of this study was to evaluate the validity, reliability, and consistency of HC app measurement compared to the current standard of practice, serving as a proof-of-concept for use by health care professionals., Methods: We recruited infants attending the neurosurgery clinic, and parents/guardians were approached and consented to participate in the study. Along with the standard head circumference measurement, measurements were taken with the head circumference app (HC app) developed in-house, and we also collected baseline medical history and characteristics. For the statistical analysis, we used RStudio (version 4.1.1). In summary, we analyzed covariance and intraclass correlation coefficient (ICC) to compare the measurement's within-rater and interrater reliability. The F test was used to analyze the variance between measurements and the Bland-Altman agreement, t test, and correlation coefficients were used to compare the tape measurement to the measures taken by the HC app. We also used nonvalidated questionnaires to explore parental or guardians' experiences, assess their views on app utility, and collect feedback., Results: The total number of recruited patients was 37. Comparison between the app measurements and the measurements with a tape measure showed poor reliability (ICC=0.177) and wide within-app variations (ICC=0.341). The agreement between the measurements done by parents/guardians and the tape measurements done by the researcher was good (ICC=0.901). Parental/guardian feedback was overall very positive, with most of the parents/guardians reporting that the app was easy to use (n=31, 84%) and that they are happy to use the app in an unsupervised setting, provided that they are assured of the measurement quality., Conclusions: We developed this project as a proof-of-concept study, and as such, the app has shown great potential to be used both in a clinical setting and by parents/guardians in their own homes., (©Stefan Yordanov, Kalsoom Akhter, Jye Quan Teh, Jawad Naushahi, Ibrahim Jalloh. Originally published in JMIR Formative Research (https://formative.jmir.org), 14.02.2024.)
- Published
- 2024
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9. Neuromonitoring in Children with Traumatic Brain Injury.
- Author
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Agrawal S, Abecasis F, and Jalloh I
- Subjects
- Child, Humans, Intracranial Pressure physiology, Cerebrovascular Circulation physiology, Brain, Brain Injuries, Traumatic therapy, Brain Injuries
- Abstract
Traumatic brain injury remains a major cause of mortality and morbidity in children across the world. Current management based on international guidelines focuses on a fixed therapeutic target of less than 20 mm Hg for managing intracranial pressure and 40-50 mm Hg for cerebral perfusion pressure across the pediatric age group. To improve outcome from this complex disease, it is essential to understand the pathophysiological mechanisms responsible for disease evolution by using different monitoring tools. In this narrative review, we discuss the neuromonitoring tools available for use to help guide management of severe traumatic brain injury in children and some of the techniques that can in future help with individualizing treatment targets based on advanced cerebral physiology monitoring., (© 2023. Crown.)
- Published
- 2024
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10. High-physiological and supra-physiological 1,2- 13 C 2 glucose focal supplementation to the traumatised human brain.
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Stovell MG, Howe DJ, Thelin EP, Jalloh I, Helmy A, Guilfoyle MR, Grice P, Mason A, Giorgi-Coll S, Gallagher CN, Murphy MP, Menon DK, Carpenter TA, Hutchinson PJ, and Carpenter KL
- Subjects
- Humans, Brain metabolism, Microdialysis, Lactic Acid metabolism, Pyruvic Acid metabolism, Dietary Supplements, Glucose metabolism, Glutamine metabolism
- Abstract
How to optimise glucose metabolism in the traumatised human brain remains unclear, including whether injured brain can metabolise additional glucose when supplied. We studied the effect of microdialysis-delivered 1,2-
13 C2 glucose at 4 and 8 mmol/L on brain extracellular chemistry using bedside ISCUS flex , and the fate of the13 C label in the 8 mmol/L group using high-resolution NMR of recovered microdialysates, in 20 patients. Compared with unsupplemented perfusion, 4 mmol/L glucose increased extracellular concentrations of pyruvate (17%, p = 0.04) and lactate (19%, p = 0.01), with a small increase in lactate/pyruvate ratio (5%, p = 0.007). Perfusion with 8 mmol/L glucose did not significantly influence extracellular chemistry measured with ISCUS flex , compared to unsupplemented perfusion. These extracellular chemistry changes appeared influenced by the underlying metabolic states of patients' traumatised brains, and the presence of relative neuroglycopaenia. Despite abundant13 C glucose supplementation, NMR revealed only 16.7%13 C enrichment of recovered extracellular lactate; the majority being glycolytic in origin. Furthermore, no13 C enrichment of TCA cycle-derived extracellular glutamine was detected. These findings indicate that a large proportion of extracellular lactate does not originate from local glucose metabolism, and taken together with our earlier studies, suggest that extracellular lactate is an important transitional step in the brain's production of glutamine., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: PJH is a Director of Technicam, the company that manufactures the triple lumen cranial access device used in the study. PJH has no competing non-financial interests with this study. The other authors have no competing financial interests.- Published
- 2023
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11. Evaluating the efficacy and safety of single-agent etoposide intra-CSF chemotherapy in children and young people with relapsed/refractory central nervous system tumours.
- Author
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Butler A, Meijer L, Liu JF, Chohan M, Jalloh I, Macarthur D, Parr M, Wilne S, Wilson S, Walker D, Grundy R, and Dandapani M
- Subjects
- Humans, Child, Adolescent, Child, Preschool, Adult, Etoposide, Antineoplastic Combined Chemotherapy Protocols, Progression-Free Survival, Quality of Life, Central Nervous System Neoplasms drug therapy
- Abstract
Purpose: The aim of the project was to evaluate intra-CSF etoposide administration in a palliative setting for children and young people with relapsed/refractory central nervous system (CNS) tumours, with the primary endpoints being overall survival and progression-free survival time. A safety endpoint was to assess the side effect profile and complications of intra-CSF etoposide., Methods: Thirty-five patients under the age of 30 years (median age: 5.33 years) were enrolled onto the project. The cross-centre study was a service evaluation, with a data collection spreadsheet designed in Nottingham and completed by both Nottingham and Oxford centres. Data was analysed using SPSS, assessing the overall survival and progression-free survival times, as well as the 6-month and 1-year survival rates., Results: The median overall survival and progression-free survival times were 10.97 and 5.91 months, respectively. The 6-month and 1-year overall survival rates were 67% and 48%, and the progression-free survival rates were 50% and 22%. Age at the start of intra-CSF therapy was significantly associated with overall survival (P = 0.046), with the 6 + age group having improved overall survival. Treatment type was significantly associated with overall survival (P = 0.012), with etoposide intra-CSF treatment being associated with improved overall survival. Treatment duration was significantly associated with both overall survival (P < 0.001) and progression-free survival (P < 0.001)., Conclusion: Intra-CSF etoposide treatment has shown to increase both overall and progression-free survival significantly, whilst having few side effects and maintaining a good quality of life for patients, reflecting it as a beneficial therapy in the palliative setting., (© 2023. Crown.)
- Published
- 2023
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12. An overview of clinical cerebral microdialysis in acute brain injury.
- Author
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Stovell MG, Helmy A, Thelin EP, Jalloh I, Hutchinson PJ, and Carpenter KLH
- Abstract
Cerebral microdialysis may be used in patients with severe brain injury to monitor their cerebral physiology. In this article we provide a concise synopsis with illustrations and original images of catheter types, their structure, and how they function. Where and how catheters are inserted, their identification on imaging modalities (CT and MRI), together with the roles of glucose, lactate/pyruvate ratio, glutamate, glycerol and urea are summarized in acute brain injury. The research applications of microdialysis including pharmacokinetic studies, retromicrodialysis, and its use as a biomarker for efficacy of potential therapies are outlined. Finally, we explore limitations and pitfalls of the technique, as well as potential improvements and future work that is needed to progress and expand the use of this technology., Competing Interests: PH was a director of Technicam (Newton Abbot, UK), the manufacturer of the cranial access device used in Cambridge. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Stovell, Helmy, Thelin, Jalloh, Hutchinson and Carpenter.)
- Published
- 2023
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13. Establishing an Antimicrobial Stewardship Program in Sierra Leone: A Report of the Experience of a Low-Income Country in West Africa.
- Author
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Lakoh S, Bawoh M, Lewis H, Jalloh I, Thomas C, Barlatt S, Jalloh A, Deen GF, Russell JBW, Kabba MS, Batema MNP, Borgstein C, Sesay N, Sesay D, Nagi NK, Firima E, and Thomas S
- Abstract
Antimicrobial Resistance (AMR) is a growing global health challenge that threatens to undo gains in human and animal health. Prevention and control of AMR requires functional antimicrobial stewardship (AMS) program, which is complex and often difficult to implement in low- and middle-income countries. We aimed to describe the processes of establishing and implementing an AMS program at Connaught Hospital in Sierra Leone. The project involved the setting up of an AMS program, capacity building and performing a global point prevalence survey (GPPS) at Sierra Leone's national referral hospital. Connaught Hospital established a multidisciplinary AMS subcommittee in 2021 to provide AMS services such as awareness campaigns, education and training and review of guidelines. We performed a GPPS on 175 patients, of whom more than half (98, 56.0%) were prescribed an antibiotic: 63 (69.2%) in the surgical wards and 53 (51.2%) in the medical wards. Ceftriaxone (60, 34.3%) and metronidazole (53, 30.3%) were the most common antibiotics prescribed to patients. In conclusion, it is feasible to establish and implement an AMS program in low-income countries, where most hospitalized patients were prescribed an antibiotic.
- Published
- 2023
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14. Recurrent posterior fossa group A (PFA) ependymoma in a young child with constitutional mismatch repair deficiency (CMMRD).
- Author
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Briggs M, Das A, Firth H, Levine A, Sánchez-Ramírez S, Negm L, Ercan AB, Chung J, Bianchi V, Jalloh I, Phyu P, Thorp N, Grundy RG, Hawkins C, Trotman J, Tarpey P, Tabori U, Allinson K, and Murray MJ
- Subjects
- Humans, Child, Mutation, Neoplastic Syndromes, Hereditary, Colorectal Neoplasms, Brain Neoplasms, Ependymoma
- Published
- 2023
- Full Text
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15. Modelling success after perinatal post-haemorrhagic hydrocephalus: a single-centre study.
- Author
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Kayhanian S, Funnell JP, Zühlsdorff K, and Jalloh I
- Subjects
- Cerebrospinal Fluid Shunts adverse effects, Child, Humans, Infant, Infant, Newborn, Infant, Premature, Retrospective Studies, Ventriculoperitoneal Shunt adverse effects, Hydrocephalus etiology, Hydrocephalus surgery, Infant, Premature, Diseases surgery
- Abstract
Introduction: Post-haemorrhagic hydrocephalus is common amongst premature infants and one of the leading indications for paediatric cerebrospinal fluid (CSF) diversion. Permanent CSF diversion is often delayed until the infant is older but there is no clear consensus on the timing for this. The outcomes for permanent shunting in this patient group are poor, with higher rates of failure and infection compared to other aetiologies of hydrocephalus., Methods: We conduct a single-centre retrospective review of infants with post-haemorrhagic hydrocephalus requiring a permanent shunt insertion over a 5-year period. Demographic and clinical data from time of shunt insertion were collected and used to generate generalised linear models (GLMs) to predict shunt success at 12 months after insertion., Results: Twenty-six infants underwent permanent shunting in this period for post-haemorrhagic hydrocephalus, with 10 suffering shunt failure within the first 12 months. The best-performing GLM was able to predict shunt success with a sensitivity of 1 and specificity of 0.90, with head circumference, weight, and corrected age at the time of shunt insertion being the most significantly associated variables for shunt success in this model., Conclusion: Our proof-of-principle study suggests that highly accurate prediction of shunt success for infants with post-haemorrhagic hydrocephalus is possible using routinely available clinical variables. Further work is required to test this model in larger cohorts and validate whether pre-operative use can improve outcomes for this patient group., (© 2022. The Author(s).)
- Published
- 2022
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16. Focally administered succinate improves cerebral metabolism in traumatic brain injury patients with mitochondrial dysfunction.
- Author
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Khellaf A, Garcia NM, Tajsic T, Alam A, Stovell MG, Killen MJ, Howe DJ, Guilfoyle MR, Jalloh I, Timofeev I, Murphy MP, Carpenter TA, Menon DK, Ercole A, Hutchinson PJ, Carpenter KL, Thelin EP, and Helmy A
- Subjects
- Adult, Female, Humans, Intracranial Pressure drug effects, Lactic Acid metabolism, Male, Microdialysis, Middle Aged, Nuclear Magnetic Resonance, Biomolecular, Pyruvic Acid metabolism, Brain metabolism, Brain Injuries, Traumatic drug therapy, Brain Injuries, Traumatic metabolism, Energy Metabolism drug effects, Mitochondria metabolism, Succinic Acid administration & dosage
- Abstract
Following traumatic brain injury (TBI), raised cerebral lactate/pyruvate ratio (LPR) reflects impaired energy metabolism. Raised LPR correlates with poor outcome and mortality following TBI. We prospectively recruited patients with TBI requiring neurocritical care and multimodal monitoring, and utilised a tiered management protocol targeting LPR. We identified patients with persistent raised LPR despite adequate cerebral glucose and oxygen provision, which we clinically classified as cerebral 'mitochondrial dysfunction' (MD). In patients with TBI and MD, we administered disodium 2,3-
13 C2 succinate (12 mmol/L) by retrodialysis into the monitored region of the brain. We recovered13 C-labelled metabolites by microdialysis and utilised nuclear magnetic resonance spectroscopy (NMR) for identification and quantification.Of 33 patients with complete monitoring, 73% had MD at some point during monitoring. In 5 patients with multimodality-defined MD, succinate administration resulted in reduced LPR(-12%) and raised brain glucose(+17%). NMR of microdialysates demonstrated that the exogenous13 C-labelled succinate was metabolised intracellularly via the tricarboxylic acid cycle. By targeting LPR using a tiered clinical algorithm incorporating intracranial pressure, brain tissue oxygenation and microdialysis parameters, we identified MD in TBI patients requiring neurointensive care. In these, focal succinate administration improved energy metabolism, evidenced by reduction in LPR. Succinate merits further investigation for TBI therapy.- Published
- 2022
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17. A map of transcriptional heterogeneity and regulatory variation in human microglia.
- Author
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Young AMH, Kumasaka N, Calvert F, Hammond TR, Knights A, Panousis N, Park JS, Schwartzentruber J, Liu J, Kundu K, Segel M, Murphy NA, McMurran CE, Bulstrode H, Correia J, Budohoski KP, Joannides A, Guilfoyle MR, Trivedi R, Kirollos R, Morris R, Garnett MR, Timofeev I, Jalloh I, Holland K, Mannion R, Mair R, Watts C, Price SJ, Kirkpatrick PJ, Santarius T, Mountjoy E, Ghoussaini M, Soranzo N, Bayraktar OA, Stevens B, Hutchinson PJ, Franklin RJM, and Gaffney DJ
- Subjects
- Alzheimer Disease genetics, Humans, Models, Genetic, Quantitative Trait Loci genetics, Sequence Analysis, RNA, Single-Cell Analysis, Gene Expression Regulation, Microglia metabolism, Transcription, Genetic
- Abstract
Microglia, the tissue-resident macrophages of the central nervous system (CNS), play critical roles in immune defense, development and homeostasis. However, isolating microglia from humans in large numbers is challenging. Here, we profiled gene expression variation in primary human microglia isolated from 141 patients undergoing neurosurgery. Using single-cell and bulk RNA sequencing, we identify how age, sex and clinical pathology influence microglia gene expression and which genetic variants have microglia-specific functions using expression quantitative trait loci (eQTL) mapping. We follow up one of our findings using a human induced pluripotent stem cell-based macrophage model to fine-map a candidate causal variant for Alzheimer's disease at the BIN1 locus. Our study provides a population-scale transcriptional map of a critically important cell for human CNS development and disease.
- Published
- 2021
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18. Changes in patterns of activity at a tertiary paediatric neurosurgical centre during the first wave of the 2020 pandemic.
- Author
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Jalloh I, Smart H, Holland KS, Zimmer-Smith HR, and Isba RE
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- Child, Humans, Tertiary Care Centers, COVID-19, Pandemics
- Published
- 2020
- Full Text
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19. Clinical utility of circulating miR-371a-3p for the management of patients with intracranial malignant germ cell tumors.
- Author
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Murray MJ, Ajithkumar T, Harris F, Williams RM, Jalloh I, Cross J, Ronghe M, Ward D, Scarpini CG, Nicholson JC, and Coleman N
- Abstract
Background: The current biomarkers alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) have limited sensitivity/specificity for diagnosing malignant germ cell tumors (GCTs) and "marker-negative" patients require histological confirmation for diagnosis. However, GCTs at intracranial sites are surgically relatively inaccessible and biopsy carries risks. MicroRNAs from the miR-371~373 and miR-302/367 clusters are over-expressed in all malignant GCTs and, in particular, miR-371a-3p shows elevated serum levels at diagnosis for testicular disease., Methods: Using our robust preamplified qRT-PCR methodology, we quantified miR-371a-3p levels in serum and cerebrospinal fluid (CSF) in a series of 4 representative clinical cases, 3 with intracranial malignant GCT and 1 with Langerhans cell histiocytosis (LCH), compared with appropriate control cases., Results: Serum and/or CSF miR-371a-3p levels distinguished those with intracranial malignant GCTs from LCH and, if known in real time, could have helped clinical management. The benefits would have included (1) the only confirmatory evidence of an intracranial malignant GCT in 1 case, supporting clinical decision making; (2) early detection of intracranial malignant GCT in another, where an elevated CSF miR-371a-3p level preceded the histologically confirmed diagnosis by 2 years; and (3) confirmation of an intracranial malignant GCT relapse with an elevated serum miR-371a-3p level, where serum and CSF AFP and HCG levels were below thresholds for such a diagnosis., Conclusions: This series highlights the potential for microRNA quantification to assist the noninvasive diagnosis, prognostication, and management for patients with intracranial malignant GCTs. Serum and CSF should be collected routinely as part of future studies to facilitate the extension of these findings to larger patient cohorts., (© The Author(s) 2020. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)
- Published
- 2020
- Full Text
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20. Feasibility of awake craniotomy in the pediatric population.
- Author
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Alcaraz García-Tejedor G, Echániz G, Strantzas S, Jalloh I, Rutka J, Drake J, and Der T
- Subjects
- Adolescent, Child, Feasibility Studies, Female, Humans, Male, Retrospective Studies, Brain Mapping methods, Craniotomy methods, Intraoperative Complications prevention & control, Monitoring, Intraoperative methods, Wakefulness
- Abstract
Background: Awake craniotomy with direct cortical stimulation and mapping is the gold standard for resection of lesions near eloquent brain areas, as it can maximize the extent of resection while minimizing the risk of neurological damage. In contrast to the adult population, only small series of awake craniotomies have been reported in children., Aims: The aim of our study is to establish the feasibility of awake craniotomy in the pediatric population., Methods: We performed a retrospective observational study of children undergoing a supratentorial awake craniotomy between January 2009 and April 2019 in a pediatric tertiary care center. Our primary outcome was feasibility of awake craniotomy, defined as the ability to complete the procedure without conversion to general anesthesia. Our secondary outcomes were the incidence of serious intraoperative complications and the mapping completion rate., Results: Thirty procedures were performed in 28 children: 12 females and 16 males. The median age was 14 years (range 7-17). The primary diagnosis was tumor (83.3%), epilepsy (13.3%), and arterio-venous malformation (3.3%). The anesthetic techniques were asleep-awake-asleep (96.7%) and conscious sedation (3.3%), all cases supplemented with scalp block and pin-site infiltration. Awake craniotomy was feasible in 29 cases (96.7%), one patient converted to general anesthesia due to agitation. Serious complications occurred in six patients: agitation (6.7%), seizures (3.3%), increased intracranial pressure (3.3%), respiratory depression (3.3%), and bradycardia (3.3%). All complications were quickly resolved and without major consequences. Cortical mapping was completed in 96.6% cases. New neurological deficits occurred in six patients (20%)-moderate in one case and mild in 5-being all absent at 6 months of follow-up., Conclusion: Awake craniotomy with intraoperative mapping can be successfully performed in children. Adequate patient selection and close cooperation between neurosurgeons, anesthesiologists, neuropsychologists, and neurophysiologists is paramount. Further studies are needed to determine the best anesthetic technique in this population group., (© 2020 John Wiley & Sons Ltd.)
- Published
- 2020
- Full Text
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21. Phosphorus spectroscopy in acute TBI demonstrates metabolic changes that relate to outcome in the presence of normal structural MRI.
- Author
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Stovell MG, Mada MO, Carpenter TA, Yan JL, Guilfoyle MR, Jalloh I, Welsh KE, Helmy A, Howe DJ, Grice P, Mason A, Giorgi-Coll S, Gallagher CN, Murphy MP, Menon DK, Hutchinson PJ, and Carpenter KL
- Subjects
- Adenosine Triphosphate metabolism, Adult, Alkalosis diagnostic imaging, Brain Injuries, Traumatic diagnostic imaging, Case-Control Studies, Energy Metabolism, Female, Humans, Male, Middle Aged, Prognosis, Brain Injuries, Traumatic metabolism, Magnetic Resonance Imaging methods, Phosphorus
- Abstract
Metabolic dysfunction is a key pathophysiological process in the acute phase of traumatic brain injury (TBI). Although changes in brain glucose metabolism and extracellular lactate/pyruvate ratio are well known, it was hitherto unknown whether these translate to downstream changes in ATP metabolism and intracellular pH. We have performed the first clinical voxel-based in vivo phosphorus magnetic resonance spectroscopy (
31 P MRS) in 13 acute-phase major TBI patients versus 10 healthy controls (HCs), at 3T, focusing on eight central 2.5 × 2.5 × 2.5 cm3 voxels per subject. PCr/γATP ratio (a measure of energy status) in TBI patients was significantly higher (median = 1.09) than that of HCs (median = 0.93) (p < 0.0001), due to changes in both PCr and ATP. There was no significant difference in PCr/γATP between TBI patients with favourable and unfavourable outcome. Cerebral intracellular pH of TBI patients was significantly higher (median = 7.04) than that of HCs (median = 7.00) (p = 0.04). Alkalosis was limited to patients with unfavourable outcome (median = 7.07) (p < 0.0001). These changes persisted after excluding voxels with > 5% radiologically visible injury. This is the first clinical demonstration of brain alkalosis and elevated PCr/γATP ratio acutely after major TBI.31 P MRS has potential for non-invasively assessing brain injury in the absence of structural injury, predicting outcome and monitoring therapy response.- Published
- 2020
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22. Modelling outcomes after paediatric brain injury with admission laboratory values: a machine-learning approach.
- Author
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Kayhanian S, Young AMH, Mangla C, Jalloh I, Fernandes HM, Garnett MR, Hutchinson PJ, and Agrawal S
- Subjects
- Child, Female, Humans, Male, Treatment Outcome, Brain Injuries therapy, Machine Learning, Patient Admission
- Abstract
Background: Severe traumatic brain injury (TBI) is a leading cause of mortality in children, but the accurate prediction of outcomes at the point of admission remains very challenging. Admission laboratory results are a promising potential source of prognostic data, but have not been widely explored in paediatric cohorts. Herein, we use machine-learning methods to analyse 14 different serum parameters together and develop a prognostic model to predict 6-month outcomes in children with severe TBI., Methods: A retrospective review of patients admitted to Cambridge University Hospital's Paediatric Intensive Care Unit between 2009 and 2013 with a TBI. The data for 14 admission serum parameters were recorded. Logistic regression and a support vector machine (SVM) were trained with these data against dichotimised outcomes from the recorded 6-month Glasgow Outcome Scale., Results: Ninety-four patients were identified. Admission levels of lactate, H+, and glucose were identified as being the most informative of 6-month outcomes. Four different models were produced. The SVM using just the three most informative parameters was the best able to predict favourable outcomes at 6 months (sensitivity = 80%, specificity = 99%)., Conclusions: Our results demonstrate the potential for highly accurate outcome prediction after severe paediatric TBI using admission laboratory data.
- Published
- 2019
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23. Correction: Modelling outcomes after paediatric brain injury with admission laboratory values: a machine-learning approach.
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Kayhanian S, Young AMH, Mangla C, Jalloh I, Fernandes HM, Garnett MR, Hutchinson PJ, and Agrawal S
- Abstract
A correction to this paper has been published and can be accessed via a link at the top of the paper.
- Published
- 2019
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24. The role of surgery in refractory epilepsy secondary to polymicrogyria in the pediatric population.
- Author
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Jalloh I, Cho N, Nga VDW, Whitney R, Jain P, Al-Mehmadi S, Yau I, Okura H, Widjaja E, Otsubo H, Ochi A, Donner E, McCoy B, Drake J, Go C, and Rutka JT
- Subjects
- Adolescent, Child, Child, Preschool, Drug Resistant Epilepsy diagnostic imaging, Female, Humans, Infant, Magnetic Resonance Imaging, Male, Polymicrogyria diagnostic imaging, Retrospective Studies, Drug Resistant Epilepsy complications, Drug Resistant Epilepsy surgery, Polymicrogyria complications, Polymicrogyria surgery, Treatment Outcome
- Abstract
Objective: Polymicrogyria (PMG) is a common malformation of cortical development. Many patients with PMG will have medically refractory epilepsy but the role of epilepsy surgery is unclear. The objective of this study was to assess the efficacy of surgical resection/disconnection in achieving seizure control in pediatric patients with PMG., Methods: A retrospective review of children undergoing epilepsy surgery for PMG between 2002 and 2017 at The Hospital for Sick Children in Toronto, Canada, was performed., Results: A total of 12 children aged 6 months to 17.8 years (median 8.8 years) underwent resective surgery (7 children) or functional hemispherectomy (5 children). Gross total resection or complete disconnection of PMG was carried out in 7 of 12 children. Follow-up duration was between 1 and 9 years (median 2.1 years). Nine children remained seizure-free at last follow-up. Complete resection or disconnection of PMG led to seizure freedom in 6 of 7 patients (86%), whereas subtotal resection produced seizure freedom in 3 of 5 patients (60%)., Significance: We present one of the largest surgical series of pediatric PMG patients. Seizure outcomes were best with complete resection/disconnection of PMG. However, tailored resections based on electroclinical and neuroradiologic data can produce good outcomes and remain an appropriate strategy for patients with extensive PMG., (Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.)
- Published
- 2018
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25. A Comparison of Oxidative Lactate Metabolism in Traumatically Injured Brain and Control Brain.
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Jalloh I, Helmy A, Howe DJ, Shannon RJ, Grice P, Mason A, Gallagher CN, Murphy MP, Pickard JD, Menon DK, Carpenter TA, Hutchinson PJ, and Carpenter KLH
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- Adolescent, Adult, Citric Acid Cycle, Dialysis, Female, Glutamine metabolism, Humans, Magnetic Resonance Spectroscopy, Male, Middle Aged, Oxidation-Reduction, Young Adult, Brain Chemistry, Brain Injuries, Traumatic metabolism, Lactic Acid metabolism
- Abstract
Metabolic abnormalities occur after traumatic brain injury (TBI). Glucose is conventionally regarded as the major energy substrate, although lactate can also be an energy source. We compared 3-
13 C lactate metabolism in TBI with "normal" control brain and muscle, measuring13 C-glutamine enrichment to assess tricarboxylic acid (TCA) cycle metabolism. Microdialysis catheters in brains of nine patients with severe TBI, five non-TBI brain surgical patients, and five resting muscle (non-TBI) patients were perfused (24 h in brain, 8 h in muscle) with 8 mmol/L sodium 3-13 C lactate. Microdialysate analysis employed ISCUS and nuclear magnetic resonance. In TBI, with 3-13 C lactate perfusion, microdialysate glucose concentration increased nonsignificantly (mean +11.9%, p = 0.463), with significant increases (p = 0.028) for lactate (+174%), pyruvate (+35.8%), and lactate/pyruvate ratio (+101.8%). Microdialysate13 C-glutamine fractional enrichments (median, interquartile range) were: for C4 5.1 (0-11.1) % in TBI and 5.7 (4.6-6.8) % in control brain, for C3 0 (0-5.0) % in TBI and 0 (0-0) % in control brain, and for C2 2.9 (0-5.7) % in TBI and 1.8 (0-3.4) % in control brain.13 C-enrichments were not statistically different between TBI and control brain, showing both metabolize 3-13 C lactate via TCA cycle, in contrast to muscle. Several patients with TBI exhibited13 C-glutamine enrichment above the non-TBI control range, suggesting lactate oxidative metabolism as a TBI "emergency option."- Published
- 2018
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26. The effect of succinate on brain NADH/NAD + redox state and high energy phosphate metabolism in acute traumatic brain injury.
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Stovell MG, Mada MO, Helmy A, Carpenter TA, Thelin EP, Yan JL, Guilfoyle MR, Jalloh I, Howe DJ, Grice P, Mason A, Giorgi-Coll S, Gallagher CN, Murphy MP, Menon DK, Hutchinson PJ, and Carpenter KLH
- Subjects
- Adenosine Triphosphate metabolism, Adult, Aged, Brain metabolism, Brain Chemistry drug effects, Female, Humans, Hydrogen-Ion Concentration drug effects, Lactic Acid metabolism, Magnetic Resonance Spectroscopy, Male, Microdialysis methods, Middle Aged, Oxidation-Reduction, Perfusion, Phosphocreatine metabolism, Pilot Projects, Prospective Studies, Pyruvic Acid metabolism, Signal Transduction drug effects, Statistics, Nonparametric, Succinic Acid administration & dosage, Succinic Acid metabolism, Treatment Outcome, Young Adult, Brain Injuries, Traumatic drug therapy, Brain Injuries, Traumatic metabolism, Energy Metabolism drug effects, NAD metabolism, Phosphates metabolism, Succinic Acid pharmacology
- Abstract
A key pathophysiological process and therapeutic target in the critical early post-injury period of traumatic brain injury (TBI) is cell mitochondrial dysfunction; characterised by elevation of brain lactate/pyruvate (L/P) ratio in the absence of hypoxia. We previously showed that succinate can improve brain extracellular chemistry in acute TBI, but it was not clear if this translates to a change in downstream energy metabolism. We studied the effect of microdialysis-delivered succinate on brain energy state (phosphocreatine/ATP ratio (PCr/ATP)) with
31 P MRS at 3T, and tissue NADH/NAD+ redox state using microdialysis (L/P ratio) in eight patients with acute major TBI (mean 7 days). Succinate perfusion was associated with increased extracellular pyruvate (+26%, p < 0.0001) and decreased L/P ratio (-13%, p < 0.0001) in patients overall (baseline-vs-supplementation over time), but no clear-cut change in31 P MRS PCr/ATP existed in our cohort (p > 0.4, supplemented-voxel-vs-contralateral voxel). However, the percentage decrease in L/P ratio for each patient following succinate perfusion correlated significantly with their percentage increase in PCr/ATP ratio (Spearman's rank correlation, r = -0.86, p = 0.024). Our findings support the interpretation that L/P ratio is linked to brain energy state, and that succinate may support brain energy metabolism in select TBI patients suffering from mitochondrial dysfunction.- Published
- 2018
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27. A cracking shot! depressed skull fracture sustained from a golf ball in a 16-year old.
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McGuinness RB, Jalloh I, and Macarthur DC
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- Child, Humans, Image Processing, Computer-Assisted, Male, Skull Fracture, Depressed diagnostic imaging, Tomography, X-Ray Computed, Golf injuries, Skull Fracture, Depressed surgery
- Abstract
Depressed skull fractures sustained from golf balls are quite rare. We report such a case in a 16-year old, and demonstrate its appearance in a 3D CT reconstruction.
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- 2017
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28. Focally perfused succinate potentiates brain metabolism in head injury patients.
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Jalloh I, Helmy A, Howe DJ, Shannon RJ, Grice P, Mason A, Gallagher CN, Stovell MG, van der Heide S, Murphy MP, Pickard JD, Menon DK, Carpenter TA, Hutchinson PJ, and Carpenter KL
- Subjects
- Adolescent, Adult, Biomarkers metabolism, Brain metabolism, Brain Chemistry drug effects, Brain Injuries, Traumatic metabolism, Citric Acid Cycle drug effects, Female, Humans, Male, Microdialysis, Middle Aged, Nuclear Magnetic Resonance, Biomolecular, Perfusion, Succinates administration & dosage, Trauma Severity Indices, Young Adult, Brain drug effects, Brain Injuries, Traumatic drug therapy, Energy Metabolism drug effects, Succinates therapeutic use
- Abstract
Following traumatic brain injury, complex cerebral energy perturbations occur. Correlating with unfavourable outcome, high brain extracellular lactate/pyruvate ratio suggests hypoxic metabolism and/or mitochondrial dysfunction. We investigated whether focal administration of succinate, a tricarboxylic acid cycle intermediate interacting directly with the mitochondrial electron transport chain, could improve cerebral metabolism. Microdialysis perfused disodium 2,3-
13 C2 succinate (12 mmol/L) for 24 h into nine sedated traumatic brain injury patients' brains, with simultaneous microdialysate collection for ISCUS analysis of energy metabolism biomarkers (nine patients) and nuclear magnetic resonance of13 C-labelled metabolites (six patients). Metabolites 2,3-13 C2 malate and 2,3-13 C2 glutamine indicated tricarboxylic acid cycle metabolism, and 2,3-13 C2 lactate suggested tricarboxylic acid cycle spinout of pyruvate (by malic enzyme or phosphoenolpyruvate carboxykinase and pyruvate kinase), then lactate dehydrogenase-mediated conversion to lactate. Versus baseline, succinate perfusion significantly decreased lactate/pyruvate ratio (p = 0.015), mean difference -12%, due to increased pyruvate concentration (+17%); lactate changed little (-3%); concentrations decreased for glutamate (-43%) (p = 0.018) and glucose (-15%) (p = 0.038). Lower lactate/pyruvate ratio suggests better redox status: cytosolic NADH recycled to NAD+ by mitochondrial shuttles (malate-aspartate and/or glycerol 3-phosphate), diminishing lactate dehydrogenase-mediated pyruvate-to-lactate conversion, and lowering glutamate. Glucose decrease suggests improved utilisation. Direct tricarboxylic acid cycle supplementation with 2,3-13 C2 succinate improved human traumatic brain injury brain chemistry, indicated by biomarkers and13 C-labelling patterns in metabolites.- Published
- 2017
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29. Advanced magnetic resonance imaging and neuropsychological assessment for detecting brain injury in a prospective cohort of university amateur boxers.
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Hart MG, Housden CR, Suckling J, Tait R, Young A, Müller U, Newcombe VFJ, Jalloh I, Pearson B, Cross J, Trivedi RA, Pickard JD, Sahakian BJ, and Hutchinson PJ
- Subjects
- Adult, Athletic Injuries pathology, Athletic Injuries physiopathology, Brain Injuries etiology, Brain Injuries pathology, Brain Injuries physiopathology, Female, Humans, Male, Prospective Studies, Universities, Young Adult, Athletic Injuries diagnosis, Boxing physiology, Brain Injuries diagnosis, Magnetic Resonance Imaging methods, Neuropsychological Tests
- Abstract
Background/aim: The safety of amateur and professional boxing is a contentious issue. We hypothesised that advanced magnetic resonance imaging and neuropsychological testing could provide evidence of acute and early brain injury in amateur boxers., Methods: We recruited 30 participants from a university amateur boxing club in a prospective cohort study. Magnetic resonance imaging (MRI) and neuropsychological testing was performed at three time points: prior to starting training; within 48 h following a first major competition to detect acute brain injury; and one year follow-up. A single MRI acquisition was made from control participants. Imaging analysis included cortical thickness measurements with Advanced Normalization Tools (ANTS) and FreeSurfer, voxel based morphometry (VBM), and Tract Based Spatial Statistics (TBSS). A computerized battery of neuropsychological tests was performed assessing attention, learning, memory and impulsivity., Results: During the study period, one boxer developed seizures controlled with medication while another developed a chronic subdural hematoma requiring neurosurgical drainage. A total of 10 boxers contributed data at to the longitudinal assessment protocol. Reasons for withdrawal were: logistics (10), stopping boxing (7), withdrawal of consent (2), and development of a chronic subdural hematoma (1). No significant changes were detected using VBM, TBSS, cortical thickness measured with FreeSurfer or ANTS, either cross-sectionally at baseline, or longitudinally. Neuropsychological assessment of boxers found attention/concentration improved over time while planning and problem solving ability latency decreased after a bout but recovered after one year., Conclusion: While this neuroimaging and neuropsychological assessment protocol could not detect any evidence of brain injury, one boxer developed seizures and another developed a chronic sub-dural haematoma.
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- 2017
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30. Continuous Multimodality Monitoring in Children after Traumatic Brain Injury-Preliminary Experience.
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Young AM, Donnelly J, Czosnyka M, Jalloh I, Liu X, Aries MJ, Fernandes HM, Garnett MR, Smielewski P, Hutchinson PJ, and Agrawal S
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- Blood Pressure, Child, Child, Preschool, Female, Humans, Intensive Care Units, Pediatric, Intracranial Pressure, Male, Prospective Studies, Brain Injuries physiopathology, Monitoring, Physiologic methods, Multimodal Imaging
- Abstract
Introduction: Multimodality monitoring is regularly employed in adult traumatic brain injury (TBI) patients where it provides physiologic and therapeutic insight into this heterogeneous condition. Pediatric studies are less frequent., Methods: An analysis of data collected prospectively from 12 pediatric TBI patients admitted to Addenbrooke's Hospital, Pediatric Intensive Care Unit (PICU) between August 2012 and December 2014 was performed. Patients' intracranial pressure (ICP), mean arterial pressure (MAP), and cerebral perfusion pressure (CPP) were monitored continuously using brain monitoring software ICM+®,) Pressure reactivity index (PRx) and 'Optimal CPP' (CPPopt) were calculated. Patient outcome was dichotomized into survivors and non-survivors., Results: At 6 months 8/12 (66%) of the cohort survived the TBI. The median (±IQR) ICP was significantly lower in survivors 13.1±3.2 mm Hg compared to non-survivors 21.6±42.9 mm Hg (p = 0.003). The median time spent with ICP over 20 mm Hg was lower in survivors (9.7+9.8% vs 60.5+67.4% in non-survivors; p = 0.003). Although there was no evidence that CPP was different between survival groups, the time spent with a CPP close (within 10 mm Hg) to the optimal CPP was significantly longer in survivors (90.7±12.6%) compared with non-survivors (70.6±21.8%; p = 0.02). PRx provided significant outcome separation with median PRx in survivors being 0.02±0.19 compared to 0.39±0.62 in non-survivors (p = 0.02)., Conclusion: Our observations provide evidence that multi-modality monitoring may be useful in pediatric TBI with ICP, deviation of CPP from CPPopt, and PRx correlating with patient outcome.
- Published
- 2016
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31. Extracellular N-Acetylaspartate in Human Traumatic Brain Injury.
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Shannon RJ, van der Heide S, Carter EL, Jalloh I, Menon DK, Hutchinson PJ, and Carpenter KL
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- Adolescent, Adult, Aged, Aspartic Acid analysis, Aspartic Acid metabolism, Biomarkers analysis, Biomarkers metabolism, Extracellular Fluid chemistry, Female, Humans, Male, Microdialysis methods, Middle Aged, Time Factors, Young Adult, Aspartic Acid analogs & derivatives, Brain Injuries, Traumatic diagnosis, Brain Injuries, Traumatic metabolism, Extracellular Fluid metabolism
- Abstract
N-acetylaspartate (NAA) is an amino acid derivative primarily located in the neurons of the adult brain. The function of NAA is incompletely understood. Decrease in brain tissue NAA is presently considered symptomatic and a potential biomarker of acute and chronic neuropathological conditions. The aim of this study was to use microdialysis to investigate the behavior of extracellular NAA (eNAA) levels after traumatic brain injury (TBI). Sampling for this study was performed using cerebral microdialysis catheters (M Dialysis 71) perfused at 0.3 μL/min. Extracellular NAA was measured in microdialysates by high-performance liquid chromatography in 30 patients with severe TBI and for comparison, in radiographically "normal" areas of brain in six non-TBI neurosurgical patients. We established a detailed temporal eNAA profile in eight of the severe TBI patients. Microdialysate concentrations of glucose, lactate, pyruvate, glutamate, and glycerol were measured on an ISCUS clinical microdialysis analyzer. Here, we show that the temporal profile of microdialysate eNAA was characterized by highest levels in the earliest time-points post-injury, followed by a steady decline; beyond 70 h post-injury, average levels were 40% lower than those measured in non-TBI patients. There was a significant inverse correlation between concentrations of eNAA and pyruvate; eNAA showed significant positive correlations with glycerol and the lactate/pyruvate (L/P) ratio measured in microdialysates. The results of this on-going study suggest that changes in eNAA after TBI relate to the release of intracellular components, possibly due to neuronal death or injury, as well as to adverse brain energy metabolism.
- Published
- 2016
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32. Consensus statement from the 2014 International Microdialysis Forum.
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Hutchinson PJ, Jalloh I, Helmy A, Carpenter KL, Rostami E, Bellander BM, Boutelle MG, Chen JW, Claassen J, Dahyot-Fizelier C, Enblad P, Gallagher CN, Helbok R, Hillered L, Le Roux PD, Magnoni S, Mangat HS, Menon DK, Nordström CH, O'Phelan KH, Oddo M, Perez Barcena J, Robertson C, Ronne-Engström E, Sahuquillo J, Smith M, Stocchetti N, Belli A, Carpenter TA, Coles JP, Czosnyka M, Dizdar N, Goodman JC, Gupta AK, Nielsen TH, Marklund N, Montcriol A, O'Connell MT, Poca MA, Sarrafzadeh A, Shannon RJ, Skjøth-Rasmussen J, Smielewski P, Stover JF, Timofeev I, Vespa P, Zavala E, and Ungerstedt U
- Subjects
- Humans, Practice Guidelines as Topic, Microdialysis methods, Microdialysis standards
- Abstract
Microdialysis enables the chemistry of the extracellular interstitial space to be monitored. Use of this technique in patients with acute brain injury has increased our understanding of the pathophysiology of several acute neurological disorders. In 2004, a consensus document on the clinical application of cerebral microdialysis was published. Since then, there have been significant advances in the clinical use of microdialysis in neurocritical care. The objective of this review is to report on the International Microdialysis Forum held in Cambridge, UK, in April 2014 and to produce a revised and updated consensus statement about its clinical use including technique, data interpretation, relationship with outcome, role in guiding therapy in neurocritical care and research applications.
- Published
- 2015
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33. Glucose metabolism following human traumatic brain injury: methods of assessment and pathophysiological findings.
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Jalloh I, Carpenter KL, Helmy A, Carpenter TA, Menon DK, and Hutchinson PJ
- Subjects
- Animals, Autoradiography methods, Brain Injuries diagnosis, Energy Metabolism physiology, Humans, Magnetic Resonance Imaging methods, Microdialysis methods, Positron-Emission Tomography methods, Brain Injuries metabolism, Brain Injuries physiopathology, Extracellular Fluid metabolism, Glucose metabolism
- Abstract
The pathophysiology of traumatic brain (TBI) injury involves changes to glucose uptake into the brain and its subsequent metabolism. We review the methods used to study cerebral glucose metabolism with a focus on those used in clinical TBI studies. Arterio-venous measurements provide a global measure of glucose uptake into the brain. Microdialysis allows the in vivo sampling of brain extracellular fluid and is well suited to the longitudinal assessment of metabolism after TBI in the clinical setting. A recent novel development is the use of microdialysis to deliver glucose and other energy substrates labelled with carbon-13, which allows the metabolism of glucose and other substrates to be tracked. Positron emission tomography and magnetic resonance spectroscopy allow regional differences in metabolism to be assessed. We summarise the data published from these techniques and review their potential uses in the clinical setting.
- Published
- 2015
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34. Glycolysis and the significance of lactate in traumatic brain injury.
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Carpenter KL, Jalloh I, and Hutchinson PJ
- Abstract
In traumatic brain injury (TBI) patients, elevation of the brain extracellular lactate concentration and the lactate/pyruvate ratio are well-recognized, and are associated statistically with unfavorable clinical outcome. Brain extracellular lactate was conventionally regarded as a waste product of glucose, when glucose is metabolized via glycolysis (Embden-Meyerhof-Parnas pathway) to pyruvate, followed by conversion to lactate by the action of lactate dehydrogenase, and export of lactate into the extracellular fluid. In TBI, glycolytic lactate is ascribed to hypoxia or mitochondrial dysfunction, although the precise nature of the latter is incompletely understood. Seemingly in contrast to lactate's association with unfavorable outcome is a growing body of evidence that lactate can be beneficial. The idea that the brain can utilize lactate by feeding into the tricarboxylic acid (TCA) cycle of neurons, first published two decades ago, has become known as the astrocyte-neuron lactate shuttle hypothesis. Direct evidence of brain utilization of lactate was first obtained 5 years ago in a cerebral microdialysis study in TBI patients, where administration of (13)C-labeled lactate via the microdialysis catheter and simultaneous collection of the emerging microdialysates, with (13)C NMR analysis, revealed (13)C labeling in glutamine consistent with lactate utilization via the TCA cycle. This suggests that where neurons are too damaged to utilize the lactate produced from glucose by astrocytes, i.e., uncoupling of neuronal and glial metabolism, high extracellular levels of lactate would accumulate, explaining the association between high lactate and poor outcome. Recently, an intravenous exogenous lactate supplementation study in TBI patients revealed evidence for a beneficial effect judged by surrogate endpoints. Here we review the current state of knowledge about glycolysis and lactate in TBI, how it can be measured in patients, and whether it can be modulated to achieve better clinical outcome.
- Published
- 2015
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35. Systemic, local, and imaging biomarkers of brain injury: more needed, and better use of those already established?
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Carpenter KL, Czosnyka M, Jalloh I, Newcombe VF, Helmy A, Shannon RJ, Budohoski KP, Kolias AG, Kirkpatrick PJ, Carpenter TA, Menon DK, and Hutchinson PJ
- Abstract
Much progress has been made over the past two decades in the treatment of severe acute brain injury, including traumatic brain injury and subarachnoid hemorrhage, resulting in a higher proportion of patients surviving with better outcomes. This has arisen from a combination of factors. These include improvements in procedures at the scene (pre-hospital) and in the hospital emergency department, advances in neuromonitoring in the intensive care unit, both continuously at the bedside and intermittently in scans, evolution and refinement of protocol-driven therapy for better management of patients, and advances in surgical procedures and rehabilitation. Nevertheless, many patients still experience varying degrees of long-term disabilities post-injury with consequent demands on carers and resources, and there is room for improvement. Biomarkers are a key aspect of neuromonitoring. A broad definition of a biomarker is any observable feature that can be used to inform on the state of the patient, e.g., a molecular species, a feature on a scan, or a monitoring characteristic, e.g., cerebrovascular pressure reactivity index. Biomarkers are usually quantitative measures, which can be utilized in diagnosis and monitoring of response to treatment. They are thus crucial to the development of therapies and may be utilized as surrogate endpoints in Phase II clinical trials. To date, there is no specific drug treatment for acute brain injury, and many seemingly promising agents emerging from pre-clinical animal models have failed in clinical trials. Large Phase III studies of clinical outcomes are costly, consuming time and resources. It is therefore important that adequate Phase II clinical studies with informative surrogate endpoints are performed employing appropriate biomarkers. In this article, we review some of the available systemic, local, and imaging biomarkers and technologies relevant in acute brain injury patients, and highlight gaps in the current state of knowledge.
- Published
- 2015
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36. Increased blood glucose is related to disturbed cerebrovascular pressure reactivity after traumatic brain injury.
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Donnelly J, Czosnyka M, Sudhan N, Varsos GV, Nasr N, Jalloh I, Liu X, Dias C, Sekhon MS, Carpenter KL, Menon DK, Hutchinson PJ, and Smielewski P
- Subjects
- Adolescent, Adult, Aged, Brain Injuries metabolism, Female, Humans, Male, Middle Aged, Retrospective Studies, Young Adult, Blood Glucose metabolism, Blood Pressure physiology, Brain Injuries physiopathology, Cerebrovascular Circulation physiology, Intracranial Pressure physiology
- Abstract
Background: Increased blood glucose and impaired pressure reactivity (PRx) after traumatic brain injury (TBI) are both known to correlate with unfavorable patient outcome. However, the relationship between these two variables is unknown., Methods: To test the hypothesis that increased blood glucose leads to increased PRx, we retrospectively analyzed data from 86 traumatic brain injured patients admitted to the Neurocritical Care Unit. Data analyzed included arterial glucose concentration, intracranial pressure (ICP), cerebral perfusion pressure (CPP) and end-tidal CO2. PRx was calculated as the moving correlation coefficient between averaged (10 seconds) arterial blood pressure and ICP. One arterial glucose concentration and one time-aligned PRx value were obtained for each patient, during each day until the fifth day after ictus., Results: Mean arterial glucose concentrations during the first 5 days since ictus were positively correlated with mean PRx (Pearson correlation coefficient = 0.25, p = 0.02). The correlation was strongest on the first day after injury (Pearson correlation coefficient = 0.47, p = 0.008)., Conclusion: Our preliminary findings indicate that increased blood glucose may impair cerebrovascular reactivity, potentially contributing to a mechanistic link between increased blood glucose and poorer outcome after TBI.
- Published
- 2015
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37. Glycolysis and the pentose phosphate pathway after human traumatic brain injury: microdialysis studies using 1,2-(13)C2 glucose.
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Jalloh I, Carpenter KL, Grice P, Howe DJ, Mason A, Gallagher CN, Helmy A, Murphy MP, Menon DK, Carpenter TA, Pickard JD, and Hutchinson PJ
- Subjects
- Adolescent, Adult, Aged, Carbon Isotopes, Case-Control Studies, Female, Humans, Lactic Acid analysis, Magnetic Resonance Spectroscopy, Male, Microdialysis, Middle Aged, Young Adult, Brain metabolism, Brain Injuries metabolism, Glucose metabolism, Glycolysis, Pentose Phosphate Pathway
- Abstract
Increased 'anaerobic' glucose metabolism is observed after traumatic brain injury (TBI) attributed to increased glycolysis. An alternative route is the pentose phosphate pathway (PPP), which generates putatively protective and reparative molecules. To compare pathways we employed microdialysis to perfuse 1,2-(13)C2 glucose into the brains of 15 TBI patients and macroscopically normal brain in six patients undergoing surgery for benign tumors, and to simultaneously collect products for nuclear magnetic resonance (NMR) analysis. (13)C enrichment for glycolytic 2,3-(13)C2 lactate was the median 5.4% (interquartile range (IQR) 4.6-7.5%) in TBI brain and 4.2% (2.4-4.4%) in 'normal' brain (P<0.01). The ratio of PPP-derived 3-(13)C lactate to glycolytic 2,3-(13)C2 lactate was median 4.9% (3.6-8.2%) in TBI brain and 6.7% (6.3-8.9%) in 'normal' brain. An inverse relationship was seen for PPP-glycolytic lactate ratio versus PbtO2 (r=-0.5, P=0.04) in TBI brain. Thus, glycolytic lactate production was significantly greater in TBI than 'normal' brain. Several TBI patients exhibited PPP-lactate elevation above the 'normal' range. There was proportionally greater PPP-derived lactate production with decreasing PbtO2. The study raises questions about the roles of the PPP and glycolysis after TBI, and whether they can be manipulated to achieve a better outcome. This study is the first direct comparison of glycolysis and PPP in human brain.
- Published
- 2015
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38. Response to letter "Lactate uptake against a concentration gradient: misinterpretation of analytical imprecision".
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Jalloh I, Helmy A, Shannon RJ, Gallagher CN, Menon DK, Carpenter KL, and Hutchinson PJ
- Subjects
- Female, Humans, Male, Brain metabolism, Brain Injuries metabolism, Cerebral Arteries metabolism, Cerebrovascular Circulation physiology, Jugular Veins metabolism, Lactic Acid metabolism
- Published
- 2014
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39. (13)C-labelled microdialysis studies of cerebral metabolism in TBI patients.
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Carpenter KL, Jalloh I, Gallagher CN, Grice P, Howe DJ, Mason A, Timofeev I, Helmy A, Murphy MP, Menon DK, Kirkpatrick PJ, Carpenter TA, Sutherland GR, Pickard JD, and Hutchinson PJ
- Subjects
- Biomarkers metabolism, Carbon-13 Magnetic Resonance Spectroscopy, Humans, Mass Spectrometry, Predictive Value of Tests, Prognosis, Brain Injuries metabolism, Energy Metabolism, Metabolomics methods, Microdialysis
- Abstract
Human brain chemistry is incompletely understood and better methodologies are needed. Traumatic brain injury (TBI) causes metabolic perturbations, one result of which includes increased brain lactate levels. Attention has largely focussed on glycolysis, whereby glucose is converted to pyruvate and lactate, and is proposed to act as an energy source by feeding into neurons' tricarboxylic acid (TCA) cycle, generating ATP. Also reportedly upregulated by TBI is the pentose phosphate pathway (PPP) that does not generate ATP but produces various molecules that are putatively neuroprotective, antioxidant and reparative, in addition to lactate among the end products. We have developed a novel combination of (13)C-labelled cerebral microdialysis both to deliver (13)C-labelled substrates into brains of TBI patients and recover the (13)C-labelled metabolites, with high-resolution (13)C NMR analysis of the microdialysates. This methodology has enabled us to achieve the first direct demonstration in humans that the brain can utilise lactate via the TCA cycle. We are currently using this methodology to make the first direct comparison of glycolysis and the PPP in human brain. In this article, we consider the application of (13)C-labelled cerebral microdialysis for studying brain energy metabolism in patients. We set this methodology within the context of metabolic pathways in the brain, and (13)C research modalities addressing them., (Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2014
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40. Giant intracranial hemangioma in a neonate.
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Jalloh I, Dean AF, O'Donovan DG, Cross J, Garnett MR, and Santarius T
- Subjects
- Brain Neoplasms congenital, Hemangioma, Capillary congenital, Hemangioma, Cavernous, Central Nervous System congenital, Humans, Infant, Newborn, Male, Brain Neoplasms pathology, Hemangioma, Capillary pathology, Hemangioma, Cavernous, Central Nervous System pathology
- Abstract
In this report we detail the case of an infant presenting with a giant intracranial congenital hemangioma and describe the clinical features and surgical management. Congenital hemangiomas are benign vascular tumors that typically present as skin lesions in neonates and infants. On rare occasions they present as intracranial tumors. The possibility that these tumors may undergo spontaneous regression poses a treatment dilemma.
- Published
- 2014
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41. Lactate uptake by the injured human brain: evidence from an arteriovenous gradient and cerebral microdialysis study.
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Jalloh I, Helmy A, Shannon RJ, Gallagher CN, Menon DK, Carpenter KL, and Hutchinson PJ
- Subjects
- Adolescent, Adult, Blood Glucose metabolism, Brain pathology, Brain Injuries diagnosis, Female, Humans, Male, Microdialysis methods, Middle Aged, Brain metabolism, Brain Injuries metabolism, Cerebral Arteries metabolism, Cerebrovascular Circulation physiology, Jugular Veins metabolism, Lactic Acid metabolism
- Abstract
Lactate has been regarded as a waste product of anaerobic metabolism of glucose. Evidence also suggests, however, that the brain may use lactate as an alternative fuel. Our aim was to determine the extent of lactate uptake from the circulation into the brain after traumatic brain injury (TBI) and to compare it with levels of lactate in the brain extracellular fluid. We recruited 19 patients with diffuse TBI, monitored with cerebral microdialysis and jugular bulb catheters. Serial arteriovenous (AV) concentration differences of glucose and lactate were calculated from arterial and jugular blood samples, providing a measure of net uptake or export by the brain. Microdialysis was used to measure brain extracellular glucose and lactate. In 17/19 patients studied for 5 days post-injury, there were periods of net lactate uptake into the brain, most frequently on day 3 after injury. Brain microdialysate lactate had a median (interquartile range [IQR]) concentration of 2.5 (1.5-3.2) mmol/L during lactate uptake and 2.2 (1.7-3.0) mmol/L during lactate export. Lactate uptake into the brain occurred at a median (IQR) arterial lactate concentration of 1.6 (1.0-2.2) mmol/L. Lactate uptake was associated with significantly higher AV difference in glucose values with a median (IQR) of 0.4 (0.03-0.7) mmol/L during uptake and 0.1 (-0.2-0.3) mmol/L during lactate export (Mann-Whitney U p=0.003). Despite relatively high brain lactate compared with arterial lactate concentrations, the brain appears to up-regulate lactate transport into the brain after TBI. This may serve to satisfy greater demands for energy substrate from the brain after TBI.
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- 2013
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42. Status dystonicus resembling the intrathecal baclofen withdrawal syndrome: a case report and review of the literature.
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Muirhead W, Jalloh I, and Vloeberghs M
- Abstract
Introduction: Status dystonicus is a rare but life-threatening disorder characterized by increasingly frequent and severe episodes of generalized dystonia that may occur in patients with primary or secondary dystonia. Painful and repetitive spasms interfere with respiration and may cause metabolic disturbances such as hyperpyrexia, dehydration, respiratory insufficiency, and acute renal failure secondary to rhabdomyolysis. Intrathecally administered baclofen, delivered by an implantable pump system, is widely used for the treatment of refractory spasticity. Abrupt cessation of intrathecal baclofen infusion has been associated with a severe withdrawal syndrome comprised of dystonia, autonomic dysfunction, hyperthermia, end-organ failure and sometimes death. The aetiology of this syndrome is not well understood. Status dystonicus describes the episodes of acute and life-threatening generalized dystonia, which occasionally manifest themselves in patients with dystonic syndromes., Case Presentation: We present the case of a nine-year-old Caucasian boy who experienced a severe episode of status dystonicus with no known cause and clinical features resembling those described in intrathecal baclofen withdrawal. Our patient subsequently underwent the placement of an intrathecal baclofen pump without incident., Conclusion: The similarity between the clinical features of the case we present and those reported in connection to abrupt withdrawal of intrathecal baclofen is emphasized. Several drugs, although not intrathecal baclofen withdrawal, have previously been associated with status dystonicus. The similarity between the life-threatening dystonic episode experienced by our patient, and those reported in intrathecal baclofen withdrawal, highlights the possibility that, rather than representing a true physiological withdrawal syndrome, abrupt withdrawal of intrathecal baclofen may simply precipitate an episode of status dystonicus in susceptible individuals. The clinical similarities between the intrathecal baclofen withdrawal syndrome and status dystonicus have not previously been highlighted.
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- 2010
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43. Spinal intradural haemorrhage in a patient with Wegener's Granulomatosis.
- Author
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Guilfoyle MR, Khan S, Helmy A, Jalloh I, Trivedi S, Trivedi R, and Kirkpatrick PJ
- Subjects
- Decompression, Surgical, Female, Hematoma, Subdural complications, Humans, Laminectomy, Lower Extremity, Magnetic Resonance Imaging, Neurosurgical Procedures, Recovery of Function, Recurrence, Spinal Diseases complications, Spine pathology, Spine surgery, Vasculitis complications, Vasculitis pathology, Young Adult, Granulomatosis with Polyangiitis complications, Hematoma, Subdural surgery, Spinal Diseases surgery
- Abstract
We describe the case of a patient with known Wegener's Granulomatosis who developed a spontaneous intradural haematoma in the thoracic spine against a background of a recent relapse in her vasculitis. Decompression resulted in a rapid recovery of lower limb function. We propose involvement of the spinal meninges in the systemic vasculitis as the cause of haemorrhage., (Copyright 2009 Elsevier B.V. All rights reserved.)
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- 2010
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44. Reactivation and centripetal spread of herpes simplex virus complicating acoustic neuroma resection.
- Author
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Jalloh I, Guilfoyle MR, Lloyd SK, Macfarlane R, and Smith C
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- Acyclovir therapeutic use, Adult, Antiviral Agents therapeutic use, Consciousness Disorders virology, DNA, Viral analysis, Encephalitis, Herpes Simplex physiopathology, Encephalitis, Herpes Simplex virology, Facial Nerve surgery, Facial Nerve virology, Facial Nerve Diseases virology, Fever virology, Humans, Magnetic Resonance Imaging, Male, Neuroma, Acoustic pathology, Neurosurgical Procedures methods, Recurrence, Tomography, X-Ray Computed, Vestibulocochlear Nerve diagnostic imaging, Vestibulocochlear Nerve pathology, Vestibulocochlear Nerve surgery, Vomiting virology, Encephalitis, Herpes Simplex etiology, Facial Nerve Diseases complications, Neuroma, Acoustic complications, Neuroma, Acoustic surgery, Neurosurgical Procedures adverse effects, Simplexvirus genetics
- Abstract
Background: Herpes simplex is a common human pathogen that has rare but severe manifestations including encephalitis., Case Description: A 44-year-old man underwent uneventful resection of an acoustic neuroma. Postoperatively, he developed swinging pyrexia, vomiting, and episodic confusion. Analysis of cerebrospinal fluid showed a lymphocytosis, and polymerase chain reaction revealed herpes simplex DNA. After treatment of herpes encephalitis with acyclovir, the patient made a good recovery., Conclusion: Herpes encephalitis is a rare complication of neurosurgical procedures, and the most likely etiology is reactivation of latent infection from manipulation of cranial nerves.
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- 2009
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45. Use of drains versus no drains after burr-hole evacuation of chronic subdural haematoma: a randomised controlled trial.
- Author
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Santarius T, Kirkpatrick PJ, Ganesan D, Chia HL, Jalloh I, Smielewski P, Richards HK, Marcus H, Parker RA, Price SJ, Kirollos RW, Pickard JD, and Hutchinson PJ
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Hematoma, Subdural, Chronic complications, Hematoma, Subdural, Chronic diagnosis, Hematoma, Subdural, Chronic mortality, Humans, Male, Middle Aged, Survival Rate, Treatment Outcome, Craniotomy, Drainage, Hematoma, Subdural, Chronic surgery
- Abstract
Background: Chronic subdural haematoma causes serious morbidity and mortality. It recurs after surgical evacuation in 5-30% of patients. Drains might reduce recurrence but are not used routinely. Our aim was to investigate the effect of drains on recurrence rates and clinical outcomes., Methods: We did a randomised controlled trial at one UK centre between November, 2004, and November, 2007. 269 patients aged 18 years and older with a chronic subdural haematoma for burr-hole drainage were assessed for eligibility. 108 were randomly assigned by block randomisation to receive a drain inserted into the subdural space and 107 to no drain after evacuation. The primary endpoint was recurrence needing redrainage. The trial was stopped early because of a significant benefit in reduction of recurrence. Analyses were done on an intention-to-treat basis. This study is registered with the International Standard Randomised Controlled Trial Register (ISRCTN 97314294)., Findings: Recurrence occurred in ten of 108 (9.3%) people with a drain, and 26 of 107 (24%) without (p=0.003; 95% CI 0.14-0.70). At 6 months mortality was nine of 105 (8.6%) and 19 of 105 (18.1%), respectively (p=0.042; 95% CI 0.1-0.99). Medical and surgical complications were much the same between the study groups., Interpretation: Use of a drain after burr-hole drainage of chronic subdural haematoma is safe and associated with reduced recurrence and mortality at 6 months., Funding: Academy of Medical Sciences, Health Foundation, and NIHR Biomedical Research Centre (Neurosciences Theme).
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- 2009
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46. Delays in the treatment of cauda equina syndrome due to its variable clinical features in patients presenting to the emergency department.
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Jalloh I and Minhas P
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- Adult, Aged, Aged, 80 and over, Anus Diseases complications, Diagnosis, Differential, Emergencies, Female, Humans, Low Back Pain complications, Magnetic Resonance Imaging, Male, Middle Aged, Movement Disorders complications, Polyradiculopathy surgery, Referral and Consultation, Reflex, Retrospective Studies, Sciatica complications, Sensation Disorders complications, Time Factors, Emergency Service, Hospital, Polyradiculopathy diagnosis
- Abstract
Objective: To identify reasons for delay in management of patients with cauda equina syndrome (CES) and to determine commonly presented features of CES., Methods: Retrospectively, the presenting features and management of patients treated for CES over a 4-year period were reviewed., Results: Reasons for delay in treatment were identified in over half of the patients., Discussion: Most patients do not present with all the characteristic features of CES. Sacral sensory loss is a sensitive and relatively specific sign for diagnosing CES.
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- 2007
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47. Some observations on onchocerciasis in the Koinadugu District of Sierra Leone.
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Tejan-Jalloh II
- Subjects
- Corneal Opacity etiology, Deafness etiology, Diethylcarbamazine administration & dosage, Diethylcarbamazine therapeutic use, Hernia, Inguinal etiology, Humans, Keratitis etiology, Male, Onchocerciasis diagnosis, Onchocerciasis drug therapy, Pruritus etiology, Sierra Leone, Testicular Hydrocele etiology, Onchocerciasis epidemiology
- Published
- 1974
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