35 results found
Dixon L, Coughlan C, Karunaratne K, et al., 2021, Immunosuppression for intracranial vasculitis associated with SARS-CoV-2: therapeutic implications for COVID-19 cerebrovascular pathology, JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, Vol: 92, Pages: 103-+, ISSN: 0022-3050
Mallas E-J, De Simoni S, Scott G, et al., 2021, Abnormal dorsal attention network activation in memory impairment after traumatic brain injury, Brain: a journal of neurology, Vol: 144, Pages: 114-127, ISSN: 0006-8950
Memory impairment is a common, disabling effect of traumatic brain injury. In healthy individuals, successful memory encoding is associated with activation of the dorsal attention network as well as suppression of the default mode network. Here, in traumatic brain injurypatients we examined whether: i) impairments in memory encoding are associated with abnormal brain activation in these networks; ii) whether changes in this brain activity predict subsequent memory retrieval; and iii) whether abnormal white matter integrity underpinningfunctional networks is associated with impaired subsequent memory. 35 patients with moderate-severetraumatic brain injury aged 23-65 years (74% males) in the post-acute/chronic phase after injury and 16 healthy controls underwent functional MRI during performance of an abstract image memory encoding task. Diffusion tensor imaging was used to assess structural abnormalities across patient groups compared to 28 age-matched healthy controls. Successful memory encoding across all participants was associated with activation of the dorsal attention network, the ventral visual stream and medial temporal lobes. Decreased activation was seen in the default mode network. Patients with preserved episodic memory demonstrated increased activation in areas of the dorsal attention network.Patients with impaired memory showed increased left anterior prefrontal activity. White matter microstructure underpinning connectivity between core nodes of the encoding networks was significantly reduced in patients with memory impairment. Our results show for the first time that patients with impaired episodic memory show abnormal activation of key nodes within the dorsal attention network and regions regulating default mode network activity during encoding. Successful encoding was associated with an opposite direction of signal
La Montanara P, Hervera A, Baltussen L, et al., 2020, Cyclin-dependent-like kinase 5 is required for pain signaling in human sensory neurons and mouse models, Science Translational Medicine, Vol: 12, Pages: 1-11, ISSN: 1946-6234
Cyclin-dependent-like kinase 5 (Cdkl5) gene mutations lead to an X-linked disorder that is characterized by infantile epileptic encephalopathy, developmental delay and hypotonia. However, we found that a substantial percentage of these patients also report a previously unrecognised anamnestic deficiency in pain perception. Consistent with a role in nociception, we discovered that Cdkl5 is expressed selectively in nociceptive dorsal root ganglia (DRG) neurons in mice and in iPS-derived human nociceptors. CDKL5 deficient mice display defective epidermal innervation and conditional deletion of Cdkl5 in DRG sensory neurons significantly impairs nociception, phenocopying CDKL5 deficiency disorder in patients. Mechanistically, Cdkl5 interacts with CaMKIIα to control outgrowth as well as TRPV1-dependent signalling, which are disrupted in both Cdkl5 mutant murine DRG and human iPS-derived nociceptors. Together, these findings unveil a previously unrecognized role for Cdkl5 in nociception, proposing an original regulatory mechanism for pain perception with implications for future therapeutics in CDKL5 deficiency disorder.
Gorgoraptis N, Kolanko M, Petridou C, et al., 2019, ACUTE PSYCHOSIS IN A YOUNG WOMAN, Annual Meeting of the Association-of-British-Neurologists (ABN), Publisher: BMJ PUBLISHING GROUP, Pages: E15-E16, ISSN: 0022-3050
Wade C, Evans M, Osugo M, et al., 2019, A QUALITY IMPROVEMENT PROJECT ON THE MANAGEMENT OF CONVULSIVE STATUS EPILEPTICUS AT ICHT, Annual Meeting of the Association-of-British-Neurologists (ABN), Publisher: BMJ PUBLISHING GROUP, Pages: E36-E36, ISSN: 0022-3050
Gorgoraptis N, Li LM, Whittington A, et al., 2019, In vivo detection of cerebral tau pathology in long-term survivors of traumatic brain injury, Science Translational Medicine, Vol: 11, Pages: 1-14, ISSN: 1946-6234
Traumatic brain injury (TBI) can trigger progressive neurodegeneration, with tau pathology seen years after a single moderate-severe TBI. Identifying this type of posttraumatic pathology in vivo might help to understand the role of tau pathology in TBI pathophysiology. We used flortaucipir positron emission tomography (PET) to investigate whether tau pathology is present many years after a single TBI in humans. We examined PET data in relation to markers of neurodegeneration in the cerebrospinal fluid (CSF), structural magnetic resonance imaging measures, and cognitive performance. Cerebral flortaucipir binding was variable, with many participants with TBI showing increases in cortical and white matter regions. At the group level, flortaucipir binding was increased in the right occipital cortex in TBI when compared to healthy controls. Flortaucipir binding was associated with increased total tau, phosphorylated tau, and ubiquitin carboxyl-terminal hydrolase L1 CSF concentrations, as well as with reduced fractional anisotropy and white matter tissue density in TBI. Apolipoprotein E (APOE) ε4 genotype affected the relationship between flortaucipir binding and time since injury, CSF β amyloid 1–42 (Aβ42) concentration, white matter tissue density, and longitudinal Mini-Mental State Examination scores in TBI. The results demonstrate that tau PET is a promising approach to investigating progressive neurodegeneration associated with tauopathy after TBI.
La Montanara P, Hervera A, Baltussen L, et al., 2019, Cyclin-dependent-like kinase 5 is required for pain signalling in both human neurons and mouse models, Publisher: bioRxiv
Abstract Cyclin-dependent-like kinase 5 ( Cdkl5) gene mutations lead to an X-linked disorder that is characterized by infantile epileptic encephalopathy, developmental delay and hypotonia. However, we found that a substantial percentage of these patients also report a previously unrecognised anamnestic deficiency in pain perception. Consistent with a role in nociception, we discovered that Cdkl5 is expressed selectively in nociceptive dorsal root ganglia (DRG) neurons in mice and in iPS-derived human nociceptors. CDKL5 deficient mice display defective epidermal innervation and conditional deletion of Cdkl5 in DRG sensory neurons significantly impairs nociception, phenocopying CDKL5 deficiency disorder in patients. Mechanistically, Cdkl5 interacts with CaMKIIα to control outgrowth as well as TRPV1-dependent signalling, which are disrupted in both Cdkl5 mutant murine DRG and human iPS-derived nociceptors. Together, these findings unveil a previously unrecognized role for Cdkl5 in nociception, proposing an original regulatory mechanism for pain perception with implications for future therapeutics in CDKL5 deficiency disorder. One Sentence Summary Cyclin-dependent-like kinase 5 (Cdkl5) controls nociception in patients and murine models of Cdkl5 deficiency disorder via CaMKII-dependent mechanisms
Gorgoraptis N, Zaw-Linn J, Feeney C, et al., 2019, Cognitive impairment and health- related quality of life following traumatic brain injury, Journal of Alzheimer's Disease, Vol: 44, Pages: 321-331, ISSN: 1387-2877
BACKGROUNDCognitive impairment is a common and disabling consequence of traumatic brain injury (TBI) but its impact on health-related quality of life is not well understood.OBJECTIVETo investigate the relationship between cognitive impairment and health-related quality of life (HRQoL) after TBI.METHODSRetrospective, cross-sectional study of a specialist TBI outpatient clinic patient sample. Outcome measures: Addenbrooke's Cognitive Examination Tool - Revised (ACE-R), and SF-36 quality of life, Beck Depression Inventory II (BDI-II), Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) questionnaires.RESULTS240 adults were assessed: n = 172 (71.7% ) moderate-severe, 41 (23.8% ) mild, 27 (11.3% ) symptomatic TBI, 174 (72.5% ) male, median age (range): 44 (22-91) years. TBI patients reported poorer scores on all domains of SF-36 compared to age-matched UK normative data. Cognitively impaired patients reported poorer HRQoL on the physical, social role and emotional role functioning, and mental health domains. Cognitive impairment predicted poorer HRQoL on the social and emotional role functioning domains, independently of depressive symptoms, sleep disturbance, daytime sleepiness and TBI severity. Mediation analysis revealed that the effect of depressive symptoms on the emotional role functioning domain of HRQoL was partially mediated by cognitive dysfunction.CONCLUSIONCognitive impairment is associated with worse health-related quality of life after TBI and partially mediates the effect of depressive symptoms on emotional role functioning.
Dalmaijer E, Li K, Gorgoraptis N, et al., 2018, A randomised double-blind, placebo-controlled crossover study of single-dose guanfacine in unilateral neglect following stroke, Journal of Neurology, Neurosurgery and Psychiatry, Vol: 89, Pages: 593-598, ISSN: 1468-330X
ObjectiveUnilateral neglect is a post-stroke disorder that impacts negatively on functional outcome and lacks established, effective treatment. This multi-component syndrome is characterised by a directional bias of attention away from contralesional space, together with impairments in several cognitive domains, including sustained attention and spatial working memory. This study aims to test the effects of guanfacine, a noradrenergic alpha-2A agonist, on ameliorating aspects of neglect.MethodsThirteen right hemisphere stroke patients with leftward neglect were included in a randomised double-blind, placebo-controlled proof-of-concept crossover study that examined the effects of a single dose ofguanfacine. Patients were tested on a computerised, time-limited cancellation paradigm, as well as tasks that independently assessed sustained attention and spatial working memory.ResultsOn guanfacine, there was a statistically significant improvement in the total number of targets found onthe cancellation task when compared to placebo (mean improvement of 5, out of a possible 64). However, there was no evidence of a change in neglect patients' directional attention bias. Furthermore,Bayesian statistical analysis revealed reliable evidence against any effects of guanfacine on search organisation and performance on our sustained attention and spatial working memory tasks. ConclusionsGuanfacine improves search in neglect by boosting the number of targets found, but had no effects on directional bias, or search organisation; nor did it improve sustained attention or working memory on independent tasks. Further work is necessary to determine whether longer-term treatment with guanfacine may be effective for some neglect patients, and whether it affects functional outcome measures.
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.
Gorgoraptis N, Li L, Whittington A, et al., 2017, [18F]AV-1451 positron emission tomography reveals tau pathology in long-term survivors of traumatic brain injury, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0028-3878
Dautricourt S, Violante I, Mallas E-J, et al., 2017, Reduced information processing speed and event-related EEG synchronization in traumatic brain injury, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0028-3878
Vanya M, Fuevesi J, Kovacs ZA, et al., 2016, NMDA-RECEPTOR ASSOCIATED ENCEPHALITIS IN A WOMAN WITH MATURE CYSTIC OVARIAN TERATOMA, IDEGGYOGYASZATI SZEMLE-CLINICAL NEUROSCIENCE, Vol: 69, Pages: 427-432, ISSN: 0019-1442
Zarkali A, Gorgoraptis N, Miller R, et al., 2016, CD8+ encephalitis: a severe but treatable HIV-related acute encephalopathy., Pract Neurol, Vol: 17, Pages: 42-46
Rapidly progressive encephalopathy in an HIV-positive patient presents a major diagnostic and management challenge. CD8+ encephalitis is a severe but treatable form of HIV-related acute encephalopathy, characterised by diffuse perivascular and intraparenchymal CD8+ lymphocytic infiltration. It can occur in patients who are apparently stable on antiretroviral treatment and probably results from viral escape into the central nervous system. Treatment, including high-dose corticosteroids, can give an excellent neurological outcome, even in people with severe encephalopathy and a very poor initial neurological status. We report a woman with CD8+ encephalitis, with a normal CD4 count and undetectable serum viral load, who made a good recovery despite the severity of her presentation.
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.
Gorgoraptis N, Zaw-Linn J, Feeney C, et al., 2015, THE IMPACT OF TRAUMATIC BRAIN INJURY ON PATIENT-REPORTED PHYSICAL AND MENTAL HEALTH, Annual Meeting of the Association-of-British-Neurologists (ABN), Publisher: BMJ PUBLISHING GROUP, ISSN: 0022-3050
Jenkins P, Fleminger J, De-Simoni S, et al., 2015, HOME COMPUTERISED COGNITIVE TESTING FOR TBI IS FEASIBLE AND POPULAR, Annual Meeting of the Association-of-British-Neurologists (ABN), Publisher: BMJ PUBLISHING GROUP, ISSN: 0022-3050
Zokaei N, Burnett Heyes S, Gorgoraptis N, et al., 2015, Working memory recall precision is a more sensitive index than span, JOURNAL OF NEUROPSYCHOLOGY, Vol: 9, Pages: 319-329, ISSN: 1748-6645
Ong YH, Jacquin-Courtois S, Gorgoraptis N, et al., 2014, Eye-Search: A web-based therapy that improves visual search in hemianopia, Annals of Clinical and Translational Neurology, Vol: 2, Pages: 74-78, ISSN: 2328-9503
Persisting hemianopia frequently complicates lesions of the posterior cerebral hemispheres, leaving patients impaired on a range of key activities of daily living. Practice-based therapies designed to induce compensatory eye movements can improve hemianopic patients' visual function, but are not readily available. We used a web-based therapy (Eye-Search) that retrains visual search saccades into patients' blind hemifield. A group of 78 suitable hemianopic patients took part. After therapy (800 trials over 11 days), search times into their impaired hemifield improved by an average of 24%. Patients also reported improvements in a subset of visually guided everyday activities, suggesting that Eye-Search therapy affects real-world outcomes.
Pertzov Y, Miller TD, Gorgoraptis N, et al., 2013, Binding deficits in memory following medial temporal lobe damage in patients with voltage-gated potassium channel complex antibody-associated limbic encephalitis, Brain, Vol: 136, Pages: 2474-2485, ISSN: 1460-2156
Some prominent studies have claimed that the medial temporal lobe is not involved in retention of information over brief intervals of just a few seconds. However, in the last decade several investigations have reported that patients with medial temporal lobe damage exhibit an abnormally large number of errors when required to remember visual information over brief intervals. But the nature of the deficit and the type of error associated with medial temporal lobe lesions remains to be fully established. Voltage-gated potassium channel complex antibody-associated limbic encephalitis has recently been recognized as a form of treatable autoimmune encephalitis, frequently associated with imaging changes in the medial temporal lobe. Here, we tested a group of these patients using two newly developed visual short-term memory tasks with a sensitive, continuous measure of report. These tests enabled us to study the nature of reporting errors, rather than only their frequency. On both paradigms, voltage-gated potassium channel complex antibody patients exhibited larger errors specifically when several items had to be remembered, but not for a single item. Crucially, their errors were strongly associated with an increased tendency to report the property of the wrong item stored in memory, rather than simple degradation of memory precision. Thus, memory for isolated aspects of items was normal, but patients were impaired at binding together the different properties belonging to an item, e.g. spatial location and object identity, or colour and orientation. This occurred regardless of whether objects were shown simultaneously or sequentially. Binding errors support the view that the medial temporal lobe is involved in linking together different types of information, potentially represented in different parts of the brain, regardless of memory duration. Our novel behavioural measures also have the potential to assist in monitoring response to treatment in patients with memory diso
Machner B, Mah Y-H, Gorgoraptis N, et al., 2012, How reliable is repeated testing for hemispatial neglect? Implications for clinical follow-up and treatment trials, JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, Vol: 83, Pages: 1032-1034, ISSN: 0022-3050
Zokaei N, Gorgoraptis N, Husain M, 2012, Dopamine modulates visual working memory precision, Journal of Vision, Vol: 12, Pages: 350-350
Gorgoraptis N, Mah Y-H, Machner B, et al., 2012, The effects of the dopamine agonist rotigotine on hemispatial neglect following stroke, BRAIN, Vol: 135, Pages: 2478-2491, ISSN: 0006-8950
Freund P, Wheeler-Kingshott CA, Nagy Z, et al., 2012, Axonal integrity predicts cortical reorganisation following cervical injury., Journal of Neurology Neurosurgery and Psychiatry, Vol: 83, Pages: 629-637, ISSN: 1468-330X
BACKGROUND: Traumatic spinal cord injury (SCI) leads to disruption of axonal architecture and macroscopic tissue loss with impaired information flow between the brain and spinal cord-the presumed basis of ensuing clinical impairment. OBJECTIVE: The authors used a clinically viable, multimodal MRI protocol to quantify the axonal integrity of the cranial corticospinal tract (CST) and to establish how microstructural white matter changes in the CST are related to cross-sectional spinal cord area and cortical reorganisation of the sensorimotor system in subjects with traumatic SCI. METHODS: Nine volunteers with cervical injuries resulting in bilateral motor impairment and 14 control subjects were studied. The authors used diffusion tensor imaging to assess white matter integrity in the CST, T1-weighted imaging to measure cross-sectional spinal cord area and functional MRI to compare motor task-related brain activations. The relationships among microstructural, macrostructural and functional measures were assessed using regression analyses. Results Diffusion tensor imaging revealed significant differences in the CST of SCI subjects-compared with controls-in the pyramids, the internal capsule, the cerebral peduncle and the hand area. The microstructural white matter changes observed in the left pyramid predicted increased task-related responses in the left M1 leg area, while changes in the cerebral peduncle were predicted by reduced cord area. CONCLUSION: The observed microstructural changes suggest trauma-related axonal degeneration and demyelination, which are related to cortical motor reorganisation and macrostructure. The extent of these changes may reflect the plasticity of motor pathways associated with cortical reorganisation. This clinically viable multimodal imaging approach is therefore appropriate for monitoring degeneration of central pathways and the evaluation of treatments targeting axonal repair in SCI.
Gorgoraptis N, Mah Y-H, Machner B, et al., 2012, Effects of the Dopamine Agonist Rotigotine on Hemispatial Neglect Following Stroke, 137th Annual Meeting of the American-Neurological-Association (ANA), Publisher: WILEY-BLACKWELL, Pages: S84-S84, ISSN: 0364-5134
Gorgoraptis N, Husain M, 2011, Improving visual neglect after right hemisphere stroke, JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, Vol: 82, Pages: 1183-1184, ISSN: 0022-3050
Goffaux V, van Zon J, Schiltz C, 2011, The horizontal tuning of face perception relies on the processing of intermediate and high spatial frequencies., J Vis, Vol: 11
It was recently shown that expert face perception relies on the extraction of horizontally oriented visual cues. Picture-plane inversion was found to eliminate horizontal, suggesting that this tuning contributes to the specificity of face processing. The present experiments sought to determine the spatial frequency (SF) scales supporting the horizontal tuning of face perception. Participants were instructed to match upright and inverted faces that were filtered both in the frequency and orientation domains. Faces in a pair contained horizontal or vertical ranges of information in low, middle, or high SF (LSF, MSF, or HSF). Our findings confirm that upright (but not inverted) face perception is tuned to horizontal orientation. Horizontal tuning was the most robust in the MSF range, next in the HSF range, and absent in the LSF range. Moreover, face inversion selectively disrupted the ability to process horizontal information in MSF and HSF ranges. This finding was replicated even when task difficulty was equated across orientation and SF at upright orientation. Our findings suggest that upright face perception is tuned to horizontally oriented face information carried by intermediate and high SF bands. They further indicate that inversion alters the sampling of face information both in the orientation and SF domains.
Gorgoraptis N, Catalao RFG, Bays PM, et al., 2011, Dynamic Updating of Working Memory Resources for Visual Objects, JOURNAL OF NEUROSCIENCE, Vol: 31, Pages: 8502-8511, ISSN: 0270-6474
Zokaei N, Gorgoraptis N, Bahrami B, et al., 2011, Precision of working memory for visual motion sequences and transparent motion surfaces, JOURNAL OF VISION, Vol: 11, ISSN: 1534-7362
Bays PM, Gorgoraptis N, Wee N, et al., 2011, Temporal dynamics of encoding, storage, and reallocation of visual working memory, JOURNAL OF VISION, Vol: 11, ISSN: 1534-7362
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