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Article ; Online: A case of limbic encephalitis associated with asymptomatic COVID-19 infection.

Zambreanu, Laura / Lightbody, Sophie / Bhandari, Mohit / Hoskote, Chandrashekar / Kandil, Hala / Houlihan, Catherine F / Lunn, Michael P

Journal of neurology, neurosurgery, and psychiatry

2020 Volume 91, Issue 11, Page(s) 1229–1230

MeSH term(s)	Aged ; Betacoronavirus ; COVID-19 ; Coronavirus Infections/complications ; Coronavirus Infections/diagnosis ; Coronavirus Infections/therapy ; Female ; Humans ; Limbic Encephalitis/diagnostic imaging ; Limbic Encephalitis/therapy ; Limbic Encephalitis/virology ; Pandemics ; Pneumonia, Viral/complications ; Pneumonia, Viral/diagnosis ; Pneumonia, Viral/therapy ; SARS-CoV-2
Keywords	covid19
Language	English
Publishing date	2020-07-13
Publishing country	England
Document type	Case Reports ; Letter
ZDB-ID	3087-9
ISSN	1468-330X ; 0022-3050
ISSN (online)	1468-330X
ISSN	0022-3050
DOI	10.1136/jnnp-2020-323839
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Book ; Online: A case of limbic encephalitis associated with asymptomatic COVID-19 infection

Zambreanu, Laura / Lightbody, Sophie / Bhandari, Mohit / Hoskote, Chandrashekar / Kandil, Hala / Houlihan, Catherine F / Lunn, Michael P

2020

Keywords	PostScript ; covid19
Language	English
Publishing date	2020-11-01 00:00:00.0
Publisher	BMJ Publishing Group Ltd
Publishing country	us
Document type	Book ; Online
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Article: A case of limbic encephalitis associated with asymptomatic COVID-19 infection

Zambreanu, Laura / Lightbody, Sophie / Bhandari, Mohit / Hoskote, Chandrashekar / Kandil, Hala / Houlihan, Catherine F / Lunn, Michael P

J Neurol Neurosurg Psychiatry

Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #650741
Database	COVID19

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Article ; Online: A case of limbic encephalitis associated with asymptomatic COVID-19 infection

Zambreanu, Laura / Lightbody, Sophie / Bhandari, Mohit / Hoskote, Chandrashekar / Kandil, Hala / Houlihan, Catherine F / Lunn, Michael P

Journal of Neurology, Neurosurgery & Psychiatry

2020 Volume 91, Issue 11, Page(s) 1229–1230

Keywords	Surgery ; Psychiatry and Mental health ; Clinical Neurology ; covid19
Language	English
Publisher	BMJ
Publishing country	uk
Document type	Article ; Online
ZDB-ID	3087-9
ISSN	1468-330X ; 0022-3050
ISSN (online)	1468-330X
ISSN	0022-3050
DOI	10.1136/jnnp-2020-323839
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Characterisation and mechanisms of bradykinin-evoked pain in man using iontophoresis.

Paterson, Kathryn J / Zambreanu, Laura / Bennett, David L H / McMahon, Stephen B

Pain

2013 Volume 154, Issue 6, Page(s) 782–792

Abstract: Bradykinin (BK) is an inflammatory mediator that can evoke oedema and vasodilatation, and is a potent algogen signalling via the B1 and B2 G-protein coupled receptors. In naïve skin, BK is effective via constitutively expressed B2 receptors (B2R), while ... ...

Abstract	Bradykinin (BK) is an inflammatory mediator that can evoke oedema and vasodilatation, and is a potent algogen signalling via the B1 and B2 G-protein coupled receptors. In naïve skin, BK is effective via constitutively expressed B2 receptors (B2R), while B1 receptors (B1R) are purported to be upregulated by inflammation. The aim of this investigation was to optimise BK delivery to investigate the algesic effects of BK and how these are modulated by inflammation. BK iontophoresis evoked dose- and temperature-dependent pain and neurogenic erythema, as well as thermal and mechanical hyperalgesia (P < 0.001 vs saline control). To differentiate the direct effects of BK from indirect effects mediated by histamine released from mast cells (MCs), skin was pretreated with compound 4880 to degranulate the MCs prior to BK challenge. The early phase of BK-evoked pain was reduced in degranulated skin (P < 0.001), while thermal and mechanical sensitisation, wheal, and flare were still evident. In contrast to BK, the B1R selective agonist des-Arg9-BK failed to induce pain or sensitise naïve skin. However, following skin inflammation induced by ultraviolet B irradiation, this compound produced a robust pain response. We have optimised a versatile experimental model by which BK and its analogues can be administered to human skin. We have found that there is an early phase of BK-induced pain which partly depends on the release of inflammatory mediators by MCs; however, subsequent hyperalgesia is not dependent on MC degranulation. In naïve skin, B2R signaling predominates, however, cutaneous inflammation results in enhanced B1R responses.
MeSH term(s)	Adult ; Bradykinin/administration & dosage ; Bradykinin/analogs & derivatives ; Edema/chemically induced ; Humans ; Inflammation/chemically induced ; Iontophoresis ; Pain/chemically induced ; Pain/physiopathology ; Pain Measurement ; Pain Threshold/drug effects ; Receptors, Bradykinin/agonists ; Skin/drug effects
Chemical Substances	Receptors, Bradykinin ; Bradykinin (S8TIM42R2W)
Language	English
Publishing date	2013-01-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	193153-2
ISSN	1872-6623 ; 0304-3959
ISSN (online)	1872-6623
ISSN	0304-3959
DOI	10.1016/j.pain.2013.01.003
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Article ; Online: Identifying brain activity specifically related to the maintenance and perceptual consequence of central sensitization in humans.

Lee, Michael C / Zambreanu, Laura / Menon, David K / Tracey, Irene

The Journal of neuroscience : the official journal of the Society for Neuroscience

2008 Volume 28, Issue 45, Page(s) 11642–11649

Abstract: Central sensitization (CS) refers to an increase in the excitability of spinal dorsal horn neurons that results from, and far outlasts the initiating nociceptive input. Here, functional magnetic resonance imaging was used to examine whether supraspinal ... ...

Abstract	Central sensitization (CS) refers to an increase in the excitability of spinal dorsal horn neurons that results from, and far outlasts the initiating nociceptive input. Here, functional magnetic resonance imaging was used to examine whether supraspinal activity might contribute to the maintenance of CS in humans. A crossover parametric design was used to distinguish and control for brain activity that is related to the consequence of increased pain experienced during CS. When the intensity of pain during CS and normal states were matched, only activity within the brainstem, including the mesencephalic pontine reticular formation, and the anterior thalami remained increased during CS. Further analyses revealed that activity in the isolated brainstem area correlated positively with the force of noxious stimulation only during CS, whereas activity in the isolated thalamic area was not modulated parametrically in either CS or normal states. Additionally, the mean activity in the isolated brainstem area was increased only during CS, whereas the mean activity in the isolated thalamic area was increased in both states, albeit less so in the normal state. Together, these findings suggest a specific role of the brainstem for the maintenance of CS in humans. Regarding brain areas related to the consequence of increased pain perception during CS, we found that only cortical activity, mainly in the primary somatosensory area, was significantly correlated with intensity of pain that was attributable to both the force of noxious stimulation used and state in which noxious stimulation was applied.
MeSH term(s)	Adult ; Analysis of Variance ; Brain/blood supply ; Brain/physiopathology ; Brain Mapping ; Brain Stem/blood supply ; Brain Stem/physiopathology ; Capsaicin/administration & dosage ; Cross-Over Studies ; Female ; Humans ; Image Processing, Computer-Assisted/methods ; Injections, Intradermal/methods ; Magnetic Resonance Imaging/methods ; Male ; Oxygen/blood ; Pain/pathology ; Pain/physiopathology ; Pain Measurement/methods ; Pain Threshold/physiology ; Physical Stimulation/adverse effects ; Psychophysics ; Skin/innervation
Chemical Substances	Capsaicin (S07O44R1ZM) ; Oxygen (S88TT14065)
Language	English
Publishing date	2008-11-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.2638-08.2008
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Article ; Online: Multiple somatotopic representations of heat and mechanical pain in the operculo-insular cortex: a high-resolution fMRI study.

Baumgärtner, Ulf / Iannetti, Gian Domenico / Zambreanu, Laura / Stoeter, Peter / Treede, Rolf-Detlef / Tracey, Irene

Journal of neurophysiology

2010 Volume 104, Issue 5, Page(s) 2863–2872

Abstract: Whereas studies of somatotopic representation of touch have been useful to distinguish multiple somatosensory areas within primary (SI) and secondary (SII) somatosensory cortex regions, no such analysis exists for the representation of pain across ... ...

Abstract	Whereas studies of somatotopic representation of touch have been useful to distinguish multiple somatosensory areas within primary (SI) and secondary (SII) somatosensory cortex regions, no such analysis exists for the representation of pain across nociceptive modalities. Here we investigated somatotopy in the operculo-insular cortex with noxious heat and pinprick stimuli in 11 healthy subjects using high-resolution (2 × 2 × 4 mm) 3T functional magnetic resonance imaging (fMRI). Heat stimuli (delivered using a laser) and pinprick stimuli (delivered using a punctate probe) were directed to the dorsum of the right hand and foot in a balanced design. Locations of the peak fMRI responses were compared between stimulation sites (hand vs. foot) and modalities (heat vs. pinprick) within four bilateral regions of interest: anterior and posterior insula and frontal and parietal operculum. Importantly, all analyses were performed on individual, non-normalized fMRI images. For heat stimuli, we found hand-foot somatotopy in the contralateral anterior and posterior insula [hand, 9 ± 10 (SD) mm anterior to foot, P < 0.05] and in the contralateral parietal operculum (SII; hand, 7 ± 10 mm lateral to foot, P < 0.05). For pinprick stimuli, we also found somatotopy in the contralateral posterior insula (hand, 9 ± 10 mm anterior to foot, P < 0.05). Furthermore, the response to heat stimulation of the hand was 11 ± 12 mm anterior to the response to pinprick stimulation of the hand in the contralateral (left) anterior insula (P < 0.05). These results indicate the existence of multiple somatotopic representations for pain within the operculo-insular region in humans, possibly reflecting its importance as a sensory-integration site that directs emotional responses and behavior appropriately depending on the body site being injured.
MeSH term(s)	Adult ; Brain Mapping ; Cerebral Cortex/physiopathology ; Female ; Hot Temperature ; Humans ; Image Processing, Computer-Assisted ; Magnetic Resonance Imaging ; Male ; Pain/physiopathology ; Pain Perception/physiology ; Pain Threshold/physiology ; Physical Stimulation
Language	English
Publishing date	2010-08-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80161-6
ISSN	1522-1598 ; 0022-3077
ISSN (online)	1522-1598
ISSN	0022-3077
DOI	10.1152/jn.00253.2010
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Article ; Online: The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings.

Paterson, Ross W / Brown, Rachel L / Benjamin, Laura / Nortley, Ross / Wiethoff, Sarah / Bharucha, Tehmina / Jayaseelan, Dipa L / Kumar, Guru / Raftopoulos, Rhian E / Zambreanu, Laura / Vivekanandam, Vinojini / Khoo, Anthony / Geraldes, Ruth / Chinthapalli, Krishna / Boyd, Elena / Tuzlali, Hatice / Price, Gary / Christofi, Gerry / Morrow, Jasper /

McNamara, Patricia / McLoughlin, Benjamin / Lim, Soon Tjin / Mehta, Puja R / Levee, Viva / Keddie, Stephen / Yong, Wisdom / Trip, S Anand / Foulkes, Alexander J M / Hotton, Gary / Miller, Thomas D / Everitt, Alex D / Carswell, Christopher / Davies, Nicholas W S / Yoong, Michael / Attwell, David / Sreedharan, Jemeen / Silber, Eli / Schott, Jonathan M / Chandratheva, Arvind / Perry, Richard J / Simister, Robert / Checkley, Anna / Longley, Nicky / Farmer, Simon F / Carletti, Francesco / Houlihan, Catherine / Thom, Maria / Lunn, Michael P / Spillane, Jennifer / Howard, Robin / Vincent, Angela / Werring, David J / Hoskote, Chandrashekar / Jäger, Hans Rolf / Manji, Hadi / Zandi, Michael S

Brain : a journal of neurology

2020 Volume 143, Issue 10, Page(s) 3104–3120

Abstract: Preliminary clinical data indicate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with neurological and neuropsychiatric illness. Responding to this, a weekly virtual coronavirus disease 19 (COVID-19) neurology ... ...

Abstract	Preliminary clinical data indicate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with neurological and neuropsychiatric illness. Responding to this, a weekly virtual coronavirus disease 19 (COVID-19) neurology multi-disciplinary meeting was established at the National Hospital, Queen Square, in early March 2020 in order to discuss and begin to understand neurological presentations in patients with suspected COVID-19-related neurological disorders. Detailed clinical and paraclinical data were collected from cases where the diagnosis of COVID-19 was confirmed through RNA PCR, or where the diagnosis was probable/possible according to World Health Organization criteria. Of 43 patients, 29 were SARS-CoV-2 PCR positive and definite, eight probable and six possible. Five major categories emerged: (i) encephalopathies (n = 10) with delirium/psychosis and no distinct MRI or CSF abnormalities, and with 9/10 making a full or partial recovery with supportive care only; (ii) inflammatory CNS syndromes (n = 12) including encephalitis (n = 2, para- or post-infectious), acute disseminated encephalomyelitis (n = 9), with haemorrhage in five, necrosis in one, and myelitis in two, and isolated myelitis (n = 1). Of these, 10 were treated with corticosteroids, and three of these patients also received intravenous immunoglobulin; one made a full recovery, 10 of 12 made a partial recovery, and one patient died; (iii) ischaemic strokes (n = 8) associated with a pro-thrombotic state (four with pulmonary thromboembolism), one of whom died; (iv) peripheral neurological disorders (n = 8), seven with Guillain-Barré syndrome, one with brachial plexopathy, six of eight making a partial and ongoing recovery; and (v) five patients with miscellaneous central disorders who did not fit these categories. SARS-CoV-2 infection is associated with a wide spectrum of neurological syndromes affecting the whole neuraxis, including the cerebral vasculature and, in some cases, responding to immunotherapies. The high incidence of acute disseminated encephalomyelitis, particularly with haemorrhagic change, is striking. This complication was not related to the severity of the respiratory COVID-19 disease. Early recognition, investigation and management of COVID-19-related neurological disease is challenging. Further clinical, neuroradiological, biomarker and neuropathological studies are essential to determine the underlying pathobiological mechanisms that will guide treatment. Longitudinal follow-up studies will be necessary to ascertain the long-term neurological and neuropsychological consequences of this pandemic.
MeSH term(s)	Adolescent ; Adrenal Cortex Hormones/therapeutic use ; Adult ; Aged ; Aged, 80 and over ; Betacoronavirus/pathogenicity ; COVID-19 ; Coronavirus Infections/drug therapy ; Coronavirus Infections/epidemiology ; Drug Utilization/statistics & numerical data ; Female ; Humans ; Immunoglobulins, Intravenous/therapeutic use ; London/epidemiology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Nervous System Diseases/cerebrospinal fluid ; Nervous System Diseases/diagnostic imaging ; Nervous System Diseases/drug therapy ; Nervous System Diseases/epidemiology ; Pandemics ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/epidemiology ; Retrospective Studies ; SARS-CoV-2 ; Young Adult
Chemical Substances	Adrenal Cortex Hormones ; Immunoglobulins, Intravenous
Keywords	covid19
Language	English
Publishing date	2020-07-01
Publishing country	England
Document type	Journal Article
ZDB-ID	80072-7
ISSN	1460-2156 ; 0006-8950
ISSN (online)	1460-2156
ISSN	0006-8950
DOI	10.1093/brain/awaa240
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Article: The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings

Brain

Abstract	Preliminary clinical data indicate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with neurological and neuropsychiatric illness. Responding to this, a weekly virtual coronavirus disease 19 (COVID-19) neurology multi-disciplinary meeting was established at the National Hospital, Queen Square, in early March 2020 in order to discuss and begin to understand neurological presentations in patients with suspected COVID-19-related neurological disorders. Detailed clinical and paraclinical data were collected from cases where the diagnosis of COVID-19 was confirmed through RNA PCR, or where the diagnosis was probable/possible according to World Health Organization criteria. Of 43 patients, 29 were SARS-CoV-2 PCR positive and definite, eight probable and six possible. Five major categories emerged: (i) encephalopathies (n = 10) with delirium/psychosis and no distinct MRI or CSF abnormalities, and with 9/10 making a full or partial recovery with supportive care only; (ii) inflammatory CNS syndromes (n = 12) including encephalitis (n = 2, para- or post-infectious), acute disseminated encephalomyelitis (n = 9), with haemorrhage in five, necrosis in one, and myelitis in two, and isolated myelitis (n = 1). Of these, 10 were treated with corticosteroids, and three of these patients also received intravenous immunoglobulin; one made a full recovery, 10 of 12 made a partial recovery, and one patient died; (iii) ischaemic strokes (n = 8) associated with a pro-thrombotic state (four with pulmonary thromboembolism), one of whom died; (iv) peripheral neurological disorders (n = 8), seven with Guillain-Barré syndrome, one with brachial plexopathy, six of eight making a partial and ongoing recovery; and (v) five patients with miscellaneous central disorders who did not fit these categories. SARS-CoV-2 infection is associated with a wide spectrum of neurological syndromes affecting the whole neuraxis, including the cerebral vasculature and, in some cases, responding to immunotherapies. The high incidence of acute disseminated encephalomyelitis, particularly with haemorrhagic change, is striking. This complication was not related to the severity of the respiratory COVID-19 disease. Early recognition, investigation and management of COVID-19-related neurological disease is challenging. Further clinical, neuroradiological, biomarker and neuropathological studies are essential to determine the underlying pathobiological mechanisms that will guide treatment. Longitudinal follow-up studies will be necessary to ascertain the long-term neurological and neuropsychological consequences of this pandemic.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #636765
Database	COVID19

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Article ; Online: The emerging spectrum of COVID-19 neurology

Brain

clinical, radiological and laboratory findings

2020 Volume 143, Issue 10, Page(s) 3104–3120

Abstract: Abstract Preliminary clinical data indicate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with neurological and neuropsychiatric illness. Responding to this, a weekly virtual coronavirus disease 19 (COVID-19) ... ...

Abstract	Abstract Preliminary clinical data indicate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with neurological and neuropsychiatric illness. Responding to this, a weekly virtual coronavirus disease 19 (COVID-19) neurology multi-disciplinary meeting was established at the National Hospital, Queen Square, in early March 2020 in order to discuss and begin to understand neurological presentations in patients with suspected COVID-19-related neurological disorders. Detailed clinical and paraclinical data were collected from cases where the diagnosis of COVID-19 was confirmed through RNA PCR, or where the diagnosis was probable/possible according to World Health Organization criteria. Of 43 patients, 29 were SARS-CoV-2 PCR positive and definite, eight probable and six possible. Five major categories emerged: (i) encephalopathies (n = 10) with delirium/psychosis and no distinct MRI or CSF abnormalities, and with 9/10 making a full or partial recovery with supportive care only; (ii) inflammatory CNS syndromes (n = 12) including encephalitis (n = 2, para- or post-infectious), acute disseminated encephalomyelitis (n = 9), with haemorrhage in five, necrosis in one, and myelitis in two, and isolated myelitis (n = 1). Of these, 10 were treated with corticosteroids, and three of these patients also received intravenous immunoglobulin; one made a full recovery, 10 of 12 made a partial recovery, and one patient died; (iii) ischaemic strokes (n = 8) associated with a pro-thrombotic state (four with pulmonary thromboembolism), one of whom died; (iv) peripheral neurological disorders (n = 8), seven with Guillain-Barré syndrome, one with brachial plexopathy, six of eight making a partial and ongoing recovery; and (v) five patients with miscellaneous central disorders who did not fit these categories. SARS-CoV-2 infection is associated with a wide spectrum of neurological syndromes affecting the whole neuraxis, including the cerebral vasculature and, in some cases, responding to immunotherapies. The high incidence of acute disseminated encephalomyelitis, particularly with haemorrhagic change, is striking. This complication was not related to the severity of the respiratory COVID-19 disease. Early recognition, investigation and management of COVID-19-related neurological disease is challenging. Further clinical, neuroradiological, biomarker and neuropathological studies are essential to determine the underlying pathobiological mechanisms that will guide treatment. Longitudinal follow-up studies will be necessary to ascertain the long-term neurological and neuropsychological consequences of this pandemic.
Keywords	Clinical Neurology ; covid19
Language	English
Publisher	Oxford University Press (OUP)
Publishing country	uk
Document type	Article ; Online
ZDB-ID	80072-7
ISSN	0006-8950
ISSN	0006-8950
DOI	10.1093/brain/awaa240
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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