Imperial College London

DrPeterJenkins

Faculty of MedicineDepartment of Medicine

Honorary Clinical Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 8064p.jenkins Website

 
 
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Location

 

C3NL LaboratoryBurlington DanesHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

20 results found

Jenkins PO, De Simoni S, Bourke NJ, Fleminger J, Scott G, Towey DJ, Svensson W, Khan S, Patel MC, Greenwood R, Friedland D, Hampshire A, Cole JH, Sharp DJet al., 2019, Stratifying drug treatment of cognitive impairments after traumatic brain injury using neuroimaging., Brain

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

JOURNAL ARTICLE

Jenkins PO, De Simoni S, Bourke N, Fleminger J, Scott G, Towey D, Svensson W, Khan S, Patel M, Greenwood R, Cole J, Sharp DJet 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

JOURNAL ARTICLE

Scott GPT, Zetterberg H, Jolly A, Cole JH, De Simoni S, Jenkins PO, Feeney C, Owen DR, Lingford-Hughes A, Howes O, Patel MC, Goldstone AP, Gunn RN, Blennow K, Matthews PM, Sharp DJet 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.

JOURNAL ARTICLE

De Simoni S, Jenkins PO, Bourke N, Fleminger JJ, Hellyer PJ, Jolly AE, Patel MC, Cole J, Leech R, Sharp DJet 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

JOURNAL ARTICLE

Feeney C, Sharp DJ, Hellyer PJ, Jolly AE, Cole JH, Scott G, Baxter D, Jilka S, Ross E, Ham TE, Jenkins PO, Li LM, Gorgoraptis N, Midwinter M, Goldstone APet 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.

JOURNAL ARTICLE

Jenkins PO, De Simoni S, Fleminger J, Bourke N, Jolly A, Cole J, Darian D, Sharp Det 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

CONFERENCE PAPER

Scott G, Jolly A, Jenkins PO, Lingford-Hughes A, Patel M, Goldstone A, Matthews P, Sharp Det 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

CONFERENCE PAPER

De Simoni S, Grover PJ, Jenkins PO, Honeyfield L, Quest R, Scott G, Wilson WH, Majewska P, Waldman AD, Patel MC, Sharp DJet 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

JOURNAL ARTICLE

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.

JOURNAL ARTICLE

Jenkins P, De Simoni S, Fleminger J, Bourke N, Jolly A, Cole J, Towey D, Sharp Det 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

CONFERENCE PAPER

Jamall O, Feeney C, Zaw-Linn J, Malik A, Niemi M, Tenorio-Jimenez C, Ham TE, Jilka SR, Jenkins PO, Scott G, Li LM, Gorgoraptis N, Baxter D, Sharp DJ, Goldstone APet 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.

JOURNAL ARTICLE

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.

JOURNAL ARTICLE

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

JOURNAL ARTICLE

Jenkins PO, Perry R, Malik O, 2014, Multiple sclerosis presenting as a relapsing amnestic syndrome., Pract Neurol, Vol: 14, Pages: 100-101

JOURNAL ARTICLE

Jenkins PO, Soper C, MacKinnon AD, O'Sullivan E, Nitkunan Aet 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.

JOURNAL ARTICLE

Reitboeck PG, Jenkins P, Pereira A, Wren Det al., 2013, STARRY NIGHTS: COMA DUE TO CEREBRAL FAT EMBOLISM SYNDROME, JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, Vol: 84, ISSN: 0022-3050

JOURNAL ARTICLE

Jenkins P, Jenkins P, 2010, In response, Clinical Medicine, Journal of the Royal College of Physicians of London, Vol: 10, ISSN: 1470-2118

JOURNAL ARTICLE

Jenkins PO, Sultanzadeh J, Bhagwat M, Jenkins PFet al., 2009, Should thrombolysis have a greater role in the management of pulmonary embolism?, CLINICAL MEDICINE, Vol: 9, Pages: 431-435, ISSN: 1470-2118

JOURNAL ARTICLE

Jenkins PO, Sultanzadeh J, Bhagwat M, Jenkins PFet 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.

JOURNAL ARTICLE

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

JOURNAL ARTICLE

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