Susannah Brain

Inflammation is increasingly recognized as part of the pathology of neurodegenerative conditions ... more Inflammation is increasingly recognized as part of the pathology of neurodegenerative conditions such as Alzheimer's disease and Parkinson's disease, but its role in dementia with Lewy bodies remains unclear. Using multimodal imaging and peripheral cytokine analysis, we therefore investigated central and peripheral inflammation in this common form of dementia. Nineteen participants with probable dementia with Lewy bodies and 16 similarly aged controls underwent 3 T MRI and PET imaging with 11 C-PK11195, a marker of microglial activation in vivo. Peripheral blood inflammatory cytokines were also measured in all subjects, as well as in an additional 10 controls, using the Mesoscale Human Cytokine 36 plex panel and additional assays for high sensitivity c-reactive protein, tumour necrosis factor receptor 1, IL-34, YKL-40 (chitinase-3-like protein 1) and colony stimulating factor 1. To test for the presence of in vivo amyloid, 11 C-Pittsburgh compound B PET imaging was also performed in 16 of the dementia with Lewy body participants. Microglial activation was elevated in dementia with Lewy bodies subjects with mild disease when compared to those with moderate/severe impairment, where disease severity was indexed by cognitive performance on the revised Addenbrooke's Cognitive Examination. In patients, strong correlations were found between cognitive performance and 11 C-PK11195 non-displaceable binding potential in several regions including the caudate nucleus (R = 0.83, P = 0.00008) and cuneus (R = 0.77, P = 0.0005). Several inflammatory cytokines were altered in the patients compared to controls, with elevated macrophage inflammatory protein-3 (P = 0.001), IL-17A (P = 0.008) and IL-2 (P = 0.046) and reduced IL-8 (P = 0.024). There was no correlation between cortical 11 C-Pittsburgh compound B standardized uptake value ratio and clinical features, regional 11 C-PK11195 binding or peripheral cytokine levels. Nor was there any regional correlation between 11 C-PK11195 non-displaceable binding potentials and 11 C-Pittsburgh compound B standardized uptake value ratios. Our findings provide evidence for both central and peripheral inflammatory changes in dementia with Lewy bodies, with microglial activation occurring early in the disease in key regions known to be associated with pathology, before declining as cognition declines. Raised peripheral cytokines associated with T cell function further suggest a role for the adaptive immune system in the pathogenesis of the disease.

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Hippocampal Stratum Radiatum, Lacunosum, and Moleculare Sparing in Mild Cognitive Impairment

Journal of Alzheimer's disease : JAD, 2018

Alzheimer's disease (AD) is associated with atrophy in entorhinal cortex (ERC), the hippocamp... more Alzheimer's disease (AD) is associated with atrophy in entorhinal cortex (ERC), the hippocampus, and its subfields Cornu Ammonis 1 (CA1) and subiculum, which predict conversion from mild cognitive impairment (MCI) to clinical AD. The stratum radiatum, lacunosum, and moleculare (SRLM) are also important gateways involving ERC and CA1, which are affected by early AD pathology. To assess whether the SRLM is affected in MCI and AD. In this proof-of-concept study, 27 controls, 13 subjects with AD, and 22 with MCI underwent 3T MRI. T1 maps were used for whole-hippocampal volumetry, T2 maps were segmented for hippocampal subfield areas, entorhinal cortex and subiculum thickness, and evaluated for SRLM integrity. Significant CA1 atrophy and subiculum thinning were found in both AD and MCI compared to similarly aged controls. However, SRLM integrity was only significantly reduced in AD but not in MCI compared to controls. There were no significant differences in other hippocampal subfiel...

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Does agomelatine block 5-HT2 C receptors in humans?

Psychopharmacology, 2011

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Diagnosing and managing psychosis in primary care

The Practitioner, May 1, 2011

Psychosis is broadly defined as the presence of delusions and hallucinations. It can be organic o... more Psychosis is broadly defined as the presence of delusions and hallucinations. It can be organic or functional. The former is secondary to an underlying medical condition, such as delirium or dementia, the latter to a psychiatric disorder, such as schizophrenia or bipolar disorder. The identification and treatment of psychosis is vital as it is associated with a 10% lifetime risk of suicide and significant social exclusion. Psychosis can be recognised by taking a thorough history, examining the patient's mental state and obtaining a collateral history. The history usually enables a distinction to be made between bipolar disorder, schizophrenia and other causes. Early symptoms often include low mood, declining educational or occupational functioning, poor motivation, changes in sleep, perceptual changes, suspiciousness and mistrust. The patient's appearance, e.g. unkempt or inappropriately attired, may reflect their predominant mental state. There may be signs of agitation, hostility or distractibility. Speech may be disorganised and difficult to follow or there may be evidence of decreased speech. Mood may be depressed or elated or change rapidly. Patients may describe abnormal thoughts and enquiry into thoughts of suicide should be routine. Disturbances of thought such as insertion or withdrawal may be present along with perceptual abnormalities i.e. illusions, hallucinations. Insight varies during the course of a psychotic illness but should be explored as it has implications for management. All patients presenting with first episode psychosis for which no organic cause can be found should be referred to the local early intervention service. In patients with a known diagnosis consider referral if there is: poor response or nonadherence to treatment; intolerable side effects; comorbid substance misuse; risk to self or others.

Seasonal variation in Guillain-Barré syndrome: a systematic review, meta-analysis and Oxfordshire cohort study

Journal of neurology, neurosurgery, and psychiatry, Jan 24, 2014

Evidence for seasonal variation in incidence and subtype of Guillain-Barré syndrome (GBS) is cont... more Evidence for seasonal variation in incidence and subtype of Guillain-Barré syndrome (GBS) is contradictory, but has implications for provision of neurological services and understanding pathogenesis. We searched PubMed and EMBASE between inception and January 2014, including all studies reporting seasonal incidence of GBS. We included a retrospective cohort study of patients with GBS at the John Radcliffe Hospital, Oxford 2001-2012 and determined the seasonal variation in GBS incidence and length of stay. The incidence rate ratio (IRR) for winter versus summer was pooled across studies by fixed and random effects meta-analysis weighted by inverse variance, stratified by geographical region, infectious prodrome and GBS subtype. Across 9836 patients from 42 studies there was a 14% increased risk of GBS in winter versus summer (IRR=1.14, 1.02-1.27, p=0.020), with significant heterogeneity between studies (I(2)=77%, p<0.0001), including significant seasonal variation in Oxford (n=140...

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Does agomelatine block 5-HT2C receptors in humans?

Psychopharmacology, 2011

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Seasonal Variation, Sub-Type and Prodromal Illnesses in Guillain-Barre Syndrome

Journal of Neurology, Neurosurgery & Psychiatry, 2013

ABSTRACT Studies have produced contradictory evidence for seasonal variation in the incidence of ... more ABSTRACT Studies have produced contradictory evidence for seasonal variation in the incidence of Guillain-Barre Syndrome (GBS), possibly due to the potentially confounding factor of the prodromal illness, for example peaks in Winter following influenza balanced by peaks in Summer due to diarrhoeal disease. The morbidity and mortality of GBS is influenced by the subtype of neuronal pathology, which may also depend upon the nature of the prodromal illness, for example axonal forms being associated with Campylobacter jejuni infection. In an attempt to study these interactions, we performed a retrospective cohort study of admission for GBS at a large teaching hospital to identify seasonal variation in incidence, subtype and associated prodromal illness. Patients admitted to the Oxford University Hospitals NHS Trust from 2001-2012 were initially identified as having a primary diagnosis of GBS by hospital coding. Seasons were defined as 3 month periods, starting from January to March (Winter). Clinical notes were then reviewed to confirm the diagnosis. Where available, the neurophysiological subtype and nature of any prodromal illness were identified. Variation in seasonal incidence was determined by chi-squared tests, and continuous variables were compared using ANOVA. Over the 11 year period, 140 patients were confirmed as having GBS, comprising 111 AIDP, 10 AMAN, 6 ASMAN, 5 Miller Fisher, 8 undetermined. There was a significant variation in seasonal incidence (p=0.037), with GBS significantly more common in Winter versus Summer (48 versus 25, p=0.007), with comparable numbers in Autumn (33) and Spring (34). A shorter average length of stay was observed in Winter compared to other seasons (15 versus 25 days, p=0.02). A specific entry regarding prodromal illness was identifiable in the clinical notes of 59/140 (42%). Of these, 22 (37%) reported an influenza-like illness, and 19 (32%) a diarrhoeal illness. In these cases, the increased incidence of GBS in Winter was partly explained by an increased incidence of GBS preceded by an influenza-like illness in Winter versus Summer (14 versus 3, p=0.012). Although there was no significant relationship between prodromal illness and GBS subtype due to the low number of axonal forms, where identifiable, all cases of AMAN had a diarrhoeal prodromal illness. In this study population, we demonstrated a significant Winter peak of GBS admissions, which we interpret as being related to the increased incidence of influenza-like illnesses. Possible factors in the significantly shorter hospital stay we observed during these peak times include less severe cases, or the increased preparedness of acute services.

Diagnosing and managing psychosis in primary care

Psychosis is broadly defined as the presence of delusions and hallucinations. It can be organic o... more Psychosis is broadly defined as the presence of delusions and hallucinations. It can be organic or functional. The former is secondary to an underlying medical condition, such as delirium or dementia, the latter to a psychiatric disorder, such as schizophrenia or bipolar disorder. The identification and treatment of psychosis is vital as it is associated with a 10% lifetime risk of suicide and significant social exclusion. Psychosis can be recognised by taking a thorough history, examining the patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s mental state and obtaining a collateral history. The history usually enables a distinction to be made between bipolar disorder, schizophrenia and other causes. Early symptoms often include low mood, declining educational or occupational functioning, poor motivation, changes in sleep, perceptual changes, suspiciousness and mistrust. The patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s appearance, e.g. unkempt or inappropriately attired, may reflect their predominant mental state. There may be signs of agitation, hostility or distractibility. Speech may be disorganised and difficult to follow or there may be evidence of decreased speech. Mood may be depressed or elated or change rapidly. Patients may describe abnormal thoughts and enquiry into thoughts of suicide should be routine. Disturbances of thought such as insertion or withdrawal may be present along with perceptual abnormalities i.e. illusions, hallucinations. Insight varies during the course of a psychotic illness but should be explored as it has implications for management. All patients presenting with first episode psychosis for which no organic cause can be found should be referred to the local early intervention service. In patients with a known diagnosis consider referral if there is: poor response or nonadherence to treatment; intolerable side effects; comorbid substance misuse; risk to self or others.

Early microglial activation and peripheral inflammation in dementia with Lewy bodies

Brain

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Hippocampal Stratum Radiatum, Lacunosum, and Moleculare Sparing in Mild Cognitive Impairment

Journal of Alzheimer's disease : JAD, 2018

Download

Does agomelatine block 5-HT2 C receptors in humans?

Psychopharmacology, 2011

Download

Diagnosing and managing psychosis in primary care

The Practitioner, May 1, 2011

Seasonal variation in Guillain-Barré syndrome: a systematic review, meta-analysis and Oxfordshire cohort study

Journal of neurology, neurosurgery, and psychiatry, Jan 24, 2014

Download

Does agomelatine block 5-HT2C receptors in humans?

Psychopharmacology, 2011

Download

Seasonal Variation, Sub-Type and Prodromal Illnesses in Guillain-Barre Syndrome

Journal of Neurology, Neurosurgery & Psychiatry, 2013

Diagnosing and managing psychosis in primary care

Psychosis is broadly defined as the presence of delusions and hallucinations. It can be organic o... more Psychosis is broadly defined as the presence of delusions and hallucinations. It can be organic or functional. The former is secondary to an underlying medical condition, such as delirium or dementia, the latter to a psychiatric disorder, such as schizophrenia or bipolar disorder. The identification and treatment of psychosis is vital as it is associated with a 10% lifetime risk of suicide and significant social exclusion. Psychosis can be recognised by taking a thorough history, examining the patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s mental state and obtaining a collateral history. The history usually enables a distinction to be made between bipolar disorder, schizophrenia and other causes. Early symptoms often include low mood, declining educational or occupational functioning, poor motivation, changes in sleep, perceptual changes, suspiciousness and mistrust. The patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s appearance, e.g. unkempt or inappropriately attired, may reflect their predominant mental state. There may be signs of agitation, hostility or distractibility. Speech may be disorganised and difficult to follow or there may be evidence of decreased speech. Mood may be depressed or elated or change rapidly. Patients may describe abnormal thoughts and enquiry into thoughts of suicide should be routine. Disturbances of thought such as insertion or withdrawal may be present along with perceptual abnormalities i.e. illusions, hallucinations. Insight varies during the course of a psychotic illness but should be explored as it has implications for management. All patients presenting with first episode psychosis for which no organic cause can be found should be referred to the local early intervention service. In patients with a known diagnosis consider referral if there is: poor response or nonadherence to treatment; intolerable side effects; comorbid substance misuse; risk to self or others.

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