24 results found
Li LM, Dilley MD, Carson A, et al., 2021, Management of traumatic brain injury (TBI): a clinical neuroscience-led pathway for the NHS., Clinical medicine (London, England), Vol: 21, Pages: e198-e205, ISSN: 1470-2118
Following hyperacute management after traumatic brain injury (TBI), most patients receive treatment which is inadequate or inappropriate, and delayed. This results in suboptimal rehabilitation outcome and avoidable detrimental chronic effects on patients' recovery. This worsens long-term disability, and magnifies costs to the individual and society. We believe that accurate diagnosis (at the level of pathology, impairment and function) of the causes of disability is a prerequisite for appropriate care and for accessing effective rehabilitation. An expert-led, integrated care pathway is needed to deliver accurate and timely diagnosis and optimal treatment at all stages during a TBI patient's care.We propose the introduction of a specialist interdisciplinary traumatic brain injury team, led by a neurosciences-trained brain injury consultant. This team would engage acutely and for a longer term after TBI to provide accurate diagnoses, which guides subsequent management and rehabilitation. This approach would also encourage more efficient collaboration between research and the clinic. We propose that the current major trauma network is leveraged to introduce and evaluate this proposal. Improvements to patient outcomes through this approach would lead to reduced personal, societal and economic impact of TBI.
Bourke N, Yanez-Lopez M, Jenkins P, et al., 2021, Traumatic brain injury: a comparison of diffusion and volumetric magnetic resonance imaging measures, Brain Communications, Vol: 3, ISSN: 2632-1297
Cognitive impairment following traumatic brain injury remains hard to predict. This is partly because axonal injury, which is of fundamental importance, is difficult to measure clinically. Advances in MRI allow axonal injury to be detected after traumatic brain injury, but the most sensitive approach is unclear. Here we compare the performance of diffusion tensor imaging, neurite orientation dispersion and density-imaging and volumetric measures of brain atrophy in the identification of white matter abnormalities after traumatic brain injury.Thirty patients with moderate-severe traumatic brain injury in the chronic phase and 20 age-matched controls had T1-weighted and diffusion MRI. Neuropsychological tests of processing speed, executive functioning and memory were used to detect cognitive impairment.Extensive abnormalities in neurite density index and orientation dispersion index were observed, with distinct spatial patterns. Fractional anisotropy and mean diffusivity also indicated widespread abnormalities of white matter structure. Neurite density index was significantly correlated with processing speed. Slower processing speed was also related to higher mean diffusivity in the cortico-spinal tracts. Lower white matter volumes were seen following brain injury with greater effect sizes compared to diffusion metrics however volume was not sensitive to changes in cognitive performance.Volume was the most sensitive at detecting change between groups but was not specific for determining relationships with cognition. Abnormalities in fractional anisotropy and mean diffusivity were the most sensitive diffusion measures, however neurite density index and orientation dispersion index may be more spatially specific. Lower neurite density index may be a useful metric for examining slower processing speed.
Jenkins P, Roussakis A-A, De Simoni S, et al., 2020, Distinct dopaminergic abnormalities in traumatic brain injury and Parkinson’s disease, Journal of Neurology, Neurosurgery and Psychiatry, Vol: 91, Pages: 631-637, ISSN: 0022-3050
Objective: Traumatic brain injury (TBI) and REM behavioural disorder (RBD) are risk factors for Parkinson’s disease (PD). Dopaminergic abnormalities are often seen after TBI, but patients usually lack parkinsonian features. We test whether TBI, PD and RBD have distinct striatal dopamine abnormalities using dopamine transporter imaging. Methods: 123I-ioflupane SPECT scans were used in a cross-sectional study to measure dopamine transporter (DaT) levels in moderate/severe TBI, healthy controls, early PD and RBD patients. Caudate and putamen DaT, putamen-to-caudate ratios and left-right symmetry of DaT were compared.Results: 108 participants (43 TBI, 26 PD, 8 RBD, 31 controls) were assessed. Early PD patients scored significantly higher on the UPDRS motor subscale than other groups. TBI and PD patients had reduced DaT levels in the caudate (12.2% and 18.7% respectively) and putamen (9.0% and 42.6% respectively) compared to controls. RBD patients had reduced DaT levels in the putamen (12.8%) but not in the caudate compared to controls. PD and TBI patients showed distinct patterns of DaT reduction, with PD patients showing a lower putamen-to-caudate ratio. DaT asymmetry was greater in the PD group than other groups. Conclusions: The results show that early PD and TBI patients have distinct patterns of striatal dopamine abnormalities. Early PD and moderate/severe TBI patients showed similar reductions in caudate DaT binding, but PD patients showed a greater reduction in putamen DaT and a lower putamen-to-caudate ratio. The results suggest that parkinsonian motor signs are absent in these TBI patients because of relatively intact putaminal dopamine levels.
Jenkins PO, De Simoni S, Bourke NJ, et al., 2019, Stratifying drug treatment of cognitive impairments after traumatic brain injury using neuroimaging, Brain, Vol: 142, Pages: 2367-2379, ISSN: 1460-2156
Cognitive impairment is common following traumatic brain injury. Dopaminergic drugs can enhance cognition after traumatic brain injury, but individual responses are highly variable. This may be due to variability in dopaminergic damage between patients. We investigate whether measuring dopamine transporter levels using 123I-ioflupane single-photon emission computed tomography (SPECT) predicts response to methylphenidate, a stimulant with dopaminergic effects. Forty patients with moderate-severe traumatic brain injury and cognitive impairments completed a randomized, double-blind, placebo-controlled, crossover study. 123I-ioflupane SPECT, MRI and neuropsychological testing were performed. Patients received 0.3 mg/kg of methylphenidate or placebo twice a day in 2-week blocks. Subjects received neuropsychological assessment after each block and completed daily home cognitive testing during the trial. The primary outcome measure was change in choice reaction time produced by methylphenidate and its relationship to stratification of patients into groups with normal and low dopamine transporter binding in the caudate. Overall, traumatic brain injury patients showed slow information processing speed. Patients with low caudate dopamine transporter binding showed improvement in response times with methylphenidate compared to placebo [median change = -16 ms; 95% confidence interval (CI): -28 to -3 ms; P = 0.02]. This represents a 27% improvement in the slowing produced by traumatic brain injury. Patients with normal dopamine transporter binding did not improve. Daily home-based choice reaction time results supported this: the low dopamine transporter group improved (median change -19 ms; 95% CI: -23 to -7 ms; P = 0.002) with no change in the normal dopamine transporter group (P = 0.50). The low dopamine transporter group also improved on self-reported and caregiver apathy assessments (P = 0.03 and P = 0.02, respectively). Both groups reported improvements in fatigue (P = 0.03
Jenkins PO, De Simoni S, Bourke N, et al., 2018, Dopaminergic abnormalities following traumatic brain injury, Brain, Vol: 141, Pages: 797-810, ISSN: 1460-2156
Traumatic brain injury can reduce striatal dopamine levels. The cause of this is uncertain, but is likely to be related to damage to the nigrostriatal system. We investigated the pattern of striatal dopamine abnormalities using 123I-Ioflupane single-photon emission computed tomography (SPECT) scans and their relationship to nigrostriatal damage and clinical features. We studied 42 moderate–severe traumatic brain injury patients with cognitive impairments but no motor parkinsonism signs and 20 healthy controls. 123I-Ioflupane scanning was used to assess dopamine transporter levels. Clinical scan reports were compared to quantitative dopamine transporter results. Advanced MRI methods were used to assess the nigrostriatal system, including the area through which the nigrostriatal projections pass as defined from high-resolution Human Connectome data. Detailed clinical and neuropsychological assessments were performed. Around 20% of our moderate–severe patients had clear evidence of reduced specific binding ratios for the dopamine transporter in the striatum measured using 123I-Ioflupane SPECT. The caudate was affected more consistently than other striatal regions. Dopamine transporter abnormalities were associated with reduced substantia nigra volume. In addition, diffusion MRI provided evidence of damage to the regions through which the nigrostriatal tract passes, particularly the area traversed by dopaminergic projections to the caudate. Only a small percentage of patients had evidence of macroscopic lesions in the striatum and there was no relationship between presence of lesions and dopamine transporter specific binding ratio abnormalities. There was also no relationship between reduced volume in the striatal subregions and reduced dopamine transporter specific binding ratios. Patients with low caudate dopamine transporter specific binding ratios show impaired processing speed and executive dysfunction compared to patients with normal levels. Taken toge
Scott GPT, Zetterberg H, Jolly A, et al., 2017, Minocycline reduces chronic microglial activation after brain trauma but increases neurodegeneration, Brain, Vol: 141, Pages: 459-471, ISSN: 1460-2156
Survivors of a traumatic brain injury can deteriorate years later, developing brain atrophy and dementia. Traumatic brain injury triggers chronic microglial activation, but it is unclear whether this is harmful or beneficial. A successful chronic-phase treatment for traumatic brain injury might be to target microglia. In experimental models, the antibiotic minocycline inhibits microglial activation. We investigated the effect of minocycline on microglial activation and neurodegeneration using PET, MRI, and measurement of the axonal protein neurofilament light in plasma. Microglial activation was assessed using 11C-PBR28 PET. The relationships of microglial activation to measures of brain injury, and the effects of minocycline on disease progression, were assessed using structural and diffusion MRI, plasma neurofilament light, and cognitive assessment. Fifteen patients at least 6 months after a moderate-to-severe traumatic brain injury received either minocycline 100 mg orally twice daily or no drug, for 12 weeks. At baseline, 11C-PBR28 binding in patients was increased compared to controls in cerebral white matter and thalamus, and plasma neurofilament light levels were elevated. MRI measures of white matter damage were highest in areas of greater 11C-PBR28 binding. Minocycline reduced 11C-PBR28 binding (mean Δwhite matter binding = −23.30%, 95% confidence interval −40.9 to −5.64%, P = 0.018), but increased plasma neurofilament light levels. Faster rates of brain atrophy were found in patients with higher baseline neurofilament light levels. In this experimental medicine study, minocycline after traumatic brain injury reduced chronic microglial activation while increasing a marker of neurodegeneration. These findings suggest that microglial activation has a reparative effect in the chronic phase of traumatic brain injury.
De Simoni S, Jenkins PO, Bourke N, et al., 2017, Altered caudate connectivity is associated with executive dysfunction after traumatic brain injury, Brain, Vol: 141, Pages: 148-164, ISSN: 1460-2156
Traumatic brain injury often produces executive dysfunction. This characteristic cognitive impairment often causes long-term problems with behaviour and personality. Frontal lobe injuries are associated with executive dysfunction, but it is unclear how these injuries relate to corticostriatal interactions that are known to play an important role in behavioural control. We hypothesized that executive dysfunction after traumatic brain injury would be associated with abnormal corticostriatal interactions, a question that has not previously been investigated. We used structural and functional MRI measures of connectivity to investigate this. Corticostriatal functional connectivity in healthy individuals was initially defined using a data-driven approach. A constrained independent component analysis approach was applied in 100 healthy adult dataset from the Human Connectome Project. Diffusion tractography was also performed to generate white matter tracts. The output of this analysis was used to compare corticostriatal functional connectivity and structural integrity between groups of 42 patients with traumatic brain injury and 21 age-matched controls. Subdivisions of the caudate and putamen had distinct patterns of functional connectivity. Traumatic brain injury patients showed disruption to functional connectivity between the caudate and a distributed set of cortical regions, including the anterior cingulate cortex. Cognitive impairments in the patients were mainly seen in processing speed and executive function, as well as increased levels of apathy and fatigue. Abnormalities of caudate functional connectivity correlated with these cognitive impairments, with reductions in right caudate connectivity associated with increased executive dysfunction, information processing speed and memory impairment. Structural connectivity, measured using diffusion tensor imaging between the caudate and anterior cingulate cortex was impaired and this also correlated with measures of ex
Feeney C, Sharp DJ, Hellyer PJ, et al., 2017, Serum IGF-I levels are associated with improved white matter recovery after TBI., Annals of Neurology, Vol: 82, Pages: 30-43, ISSN: 0364-5134
OBJECTIVE: Traumatic brain injury (TBI) is a common disabling condition with limited treatment options. Diffusion tensor imaging (DTI) measures recovery of axonal injury in white matter (WM) tracts after TBI. Growth hormone deficiency (GHD) after TBI may impair axonal and neuropsychological recovery, and serum IGF-I may mediate this effect. We conducted a longitudinal study to determine the effects of baseline serum IGF-I concentrations on WM tract and neuropsychological recovery after TBI. METHODS: Thirty-nine adults after TBI (84.6% male; age median 30.5y; 87.2% moderate-severe; time since TBI median 16.3 months, n=4 with GHD) were scanned twice, 13.3 months (12.1-14.9) apart, and 35 healthy controls scanned once. Symptom and quality of life questionnaires and cognitive assessments were completed at both visits (n=33). Our main outcome measure was fractional anisotropy (FA), a measure of WM tract integrity, in a priori regions of interest: splenium of corpus callosum (SPCC), and posterior limb of internal capsule (PLIC). RESULTS: At baseline, FA was reduced in many WM tracts including SPCC and PLIC following TBI compared to controls, indicating axonal injury, with longitudinal increases indicating axonal recovery. There was a significantly greater increase in SPCC FA over time in patients with serum IGF-I above vs. below the median-for-age. Only the higher IGF-I group had significant improvements in immediate verbal memory recall over time. INTERPRETATION: WM recovery and memory improvements after TBI were greater in patients with higher serum IGF-I at baseline. These findings suggest that GH/IGF-I system may be a potential therapeutic target following TBI. This article is protected by copyright. All rights reserved.
Jenkins PO, De Simoni S, Fleminger J, et al., 2016, Disruption to the dopaminergic system after traumatic brain injury, Annual Meeting of the Association-of-British-Neurologists (ABN), Publisher: BMJ Publishing Group, ISSN: 1468-330X
Scott G, Jolly A, Jenkins PO, et al., 2016, THE EFFECT OF MINOCYCLINE ON NEUROINFLAMMATION AFTER BRAIN TRAUMA, Annual Meeting of the Association-of-British-Neurologists (ABN), Publisher: BMJ PUBLISHING GROUP, ISSN: 0022-3050
De Simoni S, Grover PJ, Jenkins PO, et al., 2016, Disconnection between the default mode network and medial temporal lobes in post-traumatic amnesia, Brain, Vol: 139, Pages: 3137-3150, ISSN: 0006-8950
Post-traumatic amnesia is very common immediately after traumatic brain injury. It is characterised by a confused, agitated state and a pronounced inability to encode new memories and sustain attention. Clinically, post-traumatic amnesia is an important predictor of functional outcome. However, despite its prevalence and functional importance, the pathophysiology of post-traumatic amnesia is not understood. Memory processing relies on limbic structures such as the hippocampus, parahippocampus and parts of the cingulate cortex. These structures are connected within an intrinsic connectivity network, the Default Mode Network. Interactions within the Default Mode Network can be assessed using resting state functional magnetic resonance imaging, which can be acquired in confused patients unable to perform tasks in the scanner. Here we used this approach to test the hypothesis that the mnemonic symptoms of post-traumatic amnesia are caused by functional disconnection within the Default Mode Network. We assessed whether the hippocampus and parahippocampus showed evidence of transient disconnection from cortical brain regions involved in memory processing. 19 traumatic brain injury patients were classified into post-traumatic amnesia and traumatic brain injury control groups, based on their performance on a paired associates learning task. Cognitive function was also assessed with a detailed neuropsychological test battery. Functional interactions between brain regions were investigated using resting-state functional magnetic resonance imaging. Together with impairments in associative memory patients in post-traumatic amnesia demonstrated impairments in information processing speed and spatial working memory. Patients in post-traumatic amnesia showed abnormal functional connectivity between the parahippocampal gyrus and posterior cingulate cortex. The strength of this functional connection correlated with both associative memory and information processing speed and normal
Jenkins PO, Mehta MA, Sharp DJ, 2016, Catecholamines and cognition after traumatic brain injury, Brain, Vol: 139, Pages: 2345-2371, ISSN: 1935-2875
Cognitive problems are one of the main causes of ongoing disability after traumatic brain injury. The heterogeneity of the injuries sustained and the variability of the resulting cognitive deficits makes treating these problems difficult. Identifying the underlying pathology allows a targeted treatment approach aimed at cognitive enhancement. For example, damage to neuromodulatory neurotransmitter systems is common after traumatic brain injury and is an important cause of cognitive impairment. Here, we discuss the evidence implicating disruption of the catecholamines (dopamine and noradrenaline) and review the efficacy of catecholaminergic drugs in treating post-traumatic brain injury cognitive impairments. The response to these therapies is often variable, a likely consequence of the heterogeneous patterns of injury as well as a non-linear relationship between catecholamine levels and cognitive functions. This individual variability means that measuring the structure and function of a person’s catecholaminergic systems is likely to allow more refined therapy. Advanced structural and molecular imaging techniques offer the potential to identify disruption to the catecholaminergic systems and to provide a direct measure of catecholamine levels. In addition, measures of structural and functional connectivity can be used to identify common patterns of injury and to measure the functioning of brain ‘networks’ that are important for normal cognitive functioning. As the catecholamine systems modulate these cognitive networks, these measures could potentially be used to stratify treatment selection and monitor response to treatment in a more sophisticated manner.
Jenkins P, De Simoni S, Fleminger J, et al., 2016, Disruption to the dopaminergic system following traumatic brain injury, International Brain Injury Association’s Eleventh World Congress on Brain Injury, Publisher: Taylor & Francis, Pages: 670-670, ISSN: 1362-301X
Jamall O, Feeney C, Zaw-Linn J, et al., 2016, Prevalence and correlates of vitamin D deficiency in adults after traumatic brain injury, Clinical Endocrinology, Vol: 85, Pages: 636-644, ISSN: 1365-2265
Objectives: Traumatic brain injury (TBI) is a major cause of long-term disability with variable recovery. Preclinicalstudies suggest that vitamin D status influences recovery after TBI. However, there is no publishedclinical data on links between vitamin D status and TBI outcomes. To determine the: (i) prevalence ofvitamin D deficiency/insufficiency, and associations of vitamin D status with (ii) demographic factors andTBI severity, and with (iii) cognitive function, symptoms and quality of life, in adults after TBI.Design: Retrospective audit of patients seen between July 2009 and March 2015. Serum vitamin D (25-hydroxy-cholecalciferol) was categorised as deficient (<40nmol/L), insufficient (40-70nmol/L) or replete(>70nmol/L).Patients: 353 adults seen in tertiary hospital clinic (75.4% lighter-skinned, 74.8% male, age median 35.1y,range 26.6-48.3y), 0.3-56.5 months after TBI (74.5% moderate-severe).Measurements: Serum vitamin D concentrations; Addenbrooke’s Cognitive Examination (ACE-R), BeckDepression Inventory II (BDI-II), SF-36 Quality of Life, Pittsburgh Sleep Quality Index.Results: 46.5% of patients after TBI had vitamin D deficiency and 80.2% insufficiency/deficiency. Patientswith vitamin D deficiency had lower ACE-R scores than those vitamin D replete (mean effect size ± SEM 4.5± 2.1, P=0.034), and higher BDI-II scores than those vitamin D insufficient (4.5 ± 1.6, P=0.003), correcting forage, gender, time since TBI, TBI severity. There was no association between vitamin D status and markers ofTBI severity, sleep or quality of life.Conclusion: Vitamin D deficiency is common in patients after TBI and associated with impaired cognitivefunction and more severe depressive symptoms.
Sharp DJ, Jenkins PO, 2015, Concussion is confusing us all., Practical Neurology, Vol: 15, Pages: 172-186, ISSN: 1474-7766
It is time to stop using the term concussion as it has no clear definition and no pathological meaning. This confusion is increasingly problematic as the management of 'concussed' individuals is a pressing concern. Historically, it has been used to describe patients briefly disabled following a head injury, with the assumption that this was due to a transient disorder of brain function without long-term sequelae. However, the symptoms of concussion are highly variable in duration, and can persist for many years with no reliable early predictors of outcome. Using vague terminology for post-traumatic problems leads to misconceptions and biases in the diagnostic process, producing uninterpretable science, poor clinical guidelines and confused policy. We propose that the term concussion should be avoided. Instead neurologists and other healthcare professionals should classify the severity of traumatic brain injury and then attempt to precisely diagnose the underlying cause of post-traumatic symptoms.
Bantel H, Thum T, Schulze-Osthoff K, 2015, Understanding the Pathophysiological Regulatory Role of MicroRNAs in Acute Liver Failure Reply, HEPATOLOGY, Vol: 61, Pages: 1440-1441, ISSN: 0270-9139
Jenkins PO, Perry R, Malik O, 2014, Multiple sclerosis presenting as a relapsing amnestic syndrome., Pract Neurol, Vol: 14, Pages: 100-101
Jenkins PO, Soper C, MacKinnon AD, et al., 2014, Systemic Lupus Erythematosus Presenting as Orbital Myositis., Neuroophthalmology, Vol: 38, Pages: 264-267, ISSN: 0165-8107
The authors present a case of diplopia and eye pain due to orbital myositis in a patient with a de novo diagnosis of systemic lupus erythematosus. Systemic lupus erythematosus is a rare cause of orbital myositis and should be considered when other, more common, conditions have been excluded.
Reitboeck PG, Jenkins P, Pereira A, et al., 2013, STARRY NIGHTS: COMA DUE TO CEREBRAL FAT EMBOLISM SYNDROME, JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, Vol: 84, ISSN: 0022-3050
Jenkins P, Jenkins P, 2010, In response, Clinical Medicine, Journal of the Royal College of Physicians of London, Vol: 10, ISSN: 1470-2118
Jenkins PO, Sultanzadeh J, Bhagwat M, et al., 2009, Should thrombolysis have a greater role in the management of pulmonary embolism?, CLINICAL MEDICINE, Vol: 9, Pages: 431-435, ISSN: 1470-2118
Jenkins PO, Sultanzadeh J, Bhagwat M, et al., 2009, Should thrombolysis have a greater role in the management of pulmonary embolism?, Clinical Medicine, Journal of the Royal College of Physicians of London, Vol: 9, Pages: 432-435, ISSN: 1470-2118
Pulmonary embolism (PE) continues to be associated with significant mortality despite advances in the diagnostic techniques available for its detection. Anticoagulation remains standard treatment in PE although there is a consensus view that 'step-up' to thrombolytic therapy in addition to anticoagulation is indicated in those patients who are systemically shocked at presentation - a group defined as having suffered 'massive pulmonary embolism'. Considerable research has been directed at attempting to identify further groups of patients with PE who are at high risk of morbidity and mortality - notably those who are labelled as having suffered 'sub-massive pulmonary embolism' where this is defined as the presence of right-heart strain in the absence of systemic shock. In particular, the potential benefit of extending thrombolytic therapy to include those patients with sub-massive PE has been the subject of much enquiry and debate. This review examines the evidence for thrombolytic therapy and explores the potential for risk stratification in PE. © Royal College of Physicians, 2009. All rights reserved.
Jenkins PO, Turner MR, Jenkins PF, 2008, What is the place of thrombolysis in acute stroke? A review of the literature and a current perspective, CLINICAL MEDICINE, Vol: 8, Pages: 253-258, ISSN: 1470-2118
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