The cardiovascular effects of crystalloid administration in endoscopy patients.

Intravenous fluids are commonly administered for patients having colonoscopy despite relatively little data to support this practice. It is unclear what, if any, effect crystalloid administration has on stroke volume and cardiac output in patients who are fasting and have had bowel preparation agents. We aimed to assess the physiological effect of 10 ml/kg of crystalloid administration in colonoscopy patients on haemodynamic parameters including stroke volume, stroke volume variation and cardiac output, as measured with transthoracic echocardiography. Our secondary aims were to determine whether stroke volume variation predicted fluid responsiveness in gastrointestinal endoscopy patients and whether these haemodynamic measures are different in fasting patients with bowel preparation (colonoscopy patients) compared to fasting patients alone (gastroscopy patients). We recruited 54 patients having elective gastrointestinal endoscopy (25 colonoscopy, 29 gastroscopy). All patients had stroke volume, cardiac output and stroke volume variation measured with transthoracic echocardiography at baseline. In colonoscopy patients, stroke volume, cardiac output and stroke volume variation were remeasured after 10 ml/kg of intravenous crystalloid. Administration of 10 ml/kg of crystalloid increases stroke volume by 19.6 ml ( p < 0.00005) and cardiac output by 0.81 l/min ( p < 0.001). Stroke volume variation reduced from 23% to 14% after fluid administration ( p < 0.0011). The optimum threshold of stroke volume variation to predict fluid responsiveness was 21% with a sensitivity of 77.8% and specificity of 62.5%. Administration of 10 ml/kg of crystalloid increases stroke volume and cardiac output, and reduces stroke volume variation in fasting elective colonoscopy patients.

Evidence of Brain Inflammation in Patients with Human T-Lymphotropic Virus Type 1-Associated Myelopathy (HAM): A Pilot, Multimodal Imaging Study Using 11C-PBR28 PET, MR T1-Weighted, and Diffusion-Weighted Imaging.

HTLV-1-associated myelopathy (HAM; HTLV-1 is human T-lymphotropic virus type 1) is a chronic debilitating neuroinflammatory disease with a predilection for the thoracic cord. Tissue damage is attributed to the cellular immune response to HTLV-1-infected lymphocytes. The brains of HTLV-1-infected patients, with and without HAM but no clinical evidence of brain involvement, were examined using a specific 18-kDa translocator protein ligand, 11C-PBR28, and T1-weighted and diffusion-weighted MRI. METHODS: Five subjects with HAM and 2 HTLV-1 asymptomatic carriers were studied. All underwent clinical neurologic assessment including cognitive function and objective measures of gait, quantification of HTLV-1 proviral load in peripheral blood mononuclear cells, and human leukocyte antigen-antigen D related expression on circulating CD8+ lymphocytes. 11C-PBR28 PET and MRI were performed on the same day. 11C-PBR28 PET total volume of distribution and distribution volume ratio (DVR) were estimated using 2-tissue-compartment modeling. MRI data were processed using tools from the FMRIB Software Library to estimate mean diffusivity (MD) and gray matter (GM) fraction changes. The results were compared with data from age-matched healthy volunteers. RESULTS: Across the whole brain, the total volume of distribution for the subjects with HAM (5.44 ± 0.84) was significantly greater than that of asymptomatic carriers (3.44 ± 0.80). The DVR of the thalamus in patients with severe and moderate HAM was higher than that in the healthy volunteers, suggesting increased translocator protein binding (z > 4.72). Subjects with more severe myelopathy and with high DR expression on CD8+ lymphocytes had increased DVR and MD (near-significant correlation found for the right thalamus MD: P = 0.06). On the T1-weighted MRI scans, the GM fraction of the brain stem was reduced in all HTLV-1-infected patients compared with controls (P < 0.001), whereas the thalamus GM fraction was decreased in patients with HAM and correlated with the disease severity. There was no correlation between neurocognitive function and these markers of central nervous system inflammation. CONCLUSION: This pilot study suggests that some patients with HAM have asymptomatic inflammation in the brain, which can be detected and monitored by 11C-PBR28 PET together with structural and diffusion-weighted MRI.

The Language Profile of Behavioral Variant Frontotemporal Dementia.

BACKGROUND: The language profile of behavioral variant frontotemporal dementia (bvFTD) remains to be fully defined. OBJECTIVE: We aimed to quantify the extent of language deficits in this patient group. METHODS: We assessed a cohort of patients with bvFTD (n = 24) in relation to patients with semantic variant primary progressive aphasia (svPPA; n = 14), nonfluent variant primary progressive aphasia (nfvPPA; n = 18), and healthy age-matched individuals (n = 24) cross-sectionally and longitudinally using a comprehensive battery of language and general neuropsychological tests. Neuroanatomical associations of language performance were assessed using voxel-based morphometry of patients' brain magnetic resonance images. RESULTS: Relative to healthy controls, and after accounting for nonverbal executive performance, patients with bvFTD showed deficits of noun and verb naming and single word comprehension, diminished spontaneous propositional speech, and deterioration in naming performance over time. Within the bvFTD group, patients with MAPT mutations had more severe impairments of noun naming and single word comprehension than patients with C9orf72 mutations. Overall the bvFTD group had less severe language deficits than patients with PPA, but showed a language profile that was qualitatively similar to svPPA. Neuroanatomical correlates of naming and word comprehension performance in bvFTD were identified predominantly in inferior frontal and antero-inferior temporal cortices within the dominant hemispheric language network. CONCLUSIONS: bvFTD is associated with a language profile including verbal semantic impairment that warrants further evaluation as a novel biomarker.

White matter tract signatures of impaired social cognition in frontotemporal lobar degeneration.

Impairments of social cognition are often leading features in frontotemporal lobar degeneration (FTLD) and likely to reflect large-scale brain network disintegration. However, the neuroanatomical basis of impaired social cognition in FTLD and the role of white matter connections have not been defined. Here we assessed social cognition in a cohort of patients representing two core syndromes of FTLD, behavioural variant frontotemporal dementia (bvFTD; n = 29) and semantic variant primary progressive aphasia (svPPA; n = 15), relative to healthy older individuals (n = 37) using two components of the Awareness of Social Inference Test, canonical emotion identification and sarcasm identification. Diffusion tensor imaging (DTI) was used to derive white matter tract correlates of social cognition performance and compared with the distribution of grey matter atrophy on voxel-based morphometry. The bvFTD and svPPA groups showed comparably severe deficits for identification of canonical emotions and sarcasm, and these deficits were correlated with distributed and overlapping white matter tract alterations particularly affecting frontotemporal connections in the right cerebral hemisphere. The most robust DTI associations were identified in white matter tracts linking cognitive and evaluative processing with emotional responses: anterior thalamic radiation, fornix (emotion identification) and uncinate fasciculus (sarcasm identification). DTI associations of impaired social cognition were more consistent than corresponding grey matter associations. These findings delineate a brain network substrate for the social impairment that characterises FTLD syndromes. The findings further suggest that DTI can generate sensitive and functionally relevant indexes of white matter damage in FTLD, with potential to transcend conventional syndrome boundaries.

Degradation of cognitive timing mechanisms in behavioural variant frontotemporal dementia.

The current study examined motor timing in frontotemporal dementia (FTD), which manifests as progressive deterioration in social, behavioural and cognitive functions. Twenty-patients fulfilling consensus clinical criteria for behavioural variant FTD (bvFTD), 11 patients fulfilling consensus clinical criteria for semantic-variant primary progressive aphasia (svPPA), four patients fulfilling criteria for nonfluent/agrammatic primary progressive aphasia (naPPA), eight patients fulfilling criteria for Alzheimer׳s disease (AD), and 31 controls were assessed on both an externally- and self-paced finger-tapping task requiring maintenance of a regular, 1500 ms beat over 50 taps. Grey and white matter correlates of deficits in motor timing were examined using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI). bvFTD patients exhibited significant deficits in aspects of both externally- and self-paced tapping. Increased mean inter-response interval (faster than target tap time) in the self-paced task was associated with reduced grey matter volume in the cerebellum bilaterally, right middle temporal gyrus, and with increased axial diffusivity in the right superior longitudinal fasciculus, regions and tracts which have been suggested to be involved in a subcortical-cortical network of structures underlying timing abilities. This suggests that such structures can be affected in bvFTD, and that impaired motor timing may underlie some characteristics of the bvFTD phenotype.

White matter tract signatures of the progressive aphasias.

The primary progressive aphasias (PPA) are a heterogeneous group of language-led neurodegenerative diseases resulting from large-scale brain network degeneration. White matter (WM) pathways bind networks together, and might therefore hold information about PPA pathogenesis. Here we used diffusion tensor imaging and tract-based spatial statistics to compare WM tract changes between PPA syndromes and with respect to Alzheimer's disease and healthy controls in 33 patients with PPA (13 nonfluent/agrammatic PPA); 10 logopenic variant PPA; and 10 semantic variant PPA. Nonfluent/agrammatic PPA was associated with predominantly left-sided and anterior tract alterations including uncinate fasciculus (UF) and subcortical projections; semantic variant PPA with bilateral alterations in inferior longitudinal fasciculus and UF; and logopenic variant PPA with bilateral but predominantly left-sided alterations in inferior longitudinal fasciculus, UF, superior longitudinal fasciculus, and subcortical projections. Tract alterations were more extensive than gray matter alterations, and the extent of alteration across tracts and PPA syndromes varied between diffusivity metrics. These WM signatures of PPA syndromes illustrate the selective vulnerability of brain language networks in these diseases and might have some pathologic specificity.

Flavour identification in frontotemporal lobar degeneration.

BACKGROUND: Deficits of flavour processing may be clinically important in frontotemporal lobar degeneration (FTLD). OBJECTIVE: To examine flavour processing in FTLD. METHODS: We studied flavour identification prospectively in 25 patients with FTLD (12 with behavioural variant frontotemporal dementia (bvFTD), eight with semantic variant primary progressive aphasia (svPPA), five with non-fluent variant primary progressive aphasia (nfvPPA)) and 17 healthy control subjects, using a new test based on cross-modal matching of flavours to words and pictures. All subjects completed a general neuropsychological assessment, and odour identification was also assessed using a modified University of Pennsylvania Smell Identification Test. Brain MRI volumes from the patient cohort were analysed using voxel-based morphometry to identify regional grey matter associations of flavour identification. RESULTS: Relative to the healthy control group, the bvFTD and svPPA subgroups showed significant (p<0.05) deficits of flavour identification and all three FTLD subgroups showed deficits of odour identification. Flavour identification performance did not differ significantly between the FTLD syndromic subgroups. Flavour identification performance in the combined FTLD cohort was significantly (p<0.05 after multiple comparisons correction) associated with grey matter volume in the left entorhinal cortex, hippocampus, parahippocampal gyrus and temporal pole. CONCLUSIONS: Certain FTLD syndromes are associated with impaired flavour identification and this is underpinned by grey matter atrophy in an anteromedial temporal lobe network. These findings may have implications for our understanding of abnormal eating behaviour in these diseases.

Impairments of auditory scene analysis in Alzheimer's disease.

Parsing of sound sources in the auditory environment or 'auditory scene analysis' is a computationally demanding cognitive operation that is likely to be vulnerable to the neurodegenerative process in Alzheimer's disease. However, little information is available concerning auditory scene analysis in Alzheimer's disease. Here we undertook a detailed neuropsychological and neuroanatomical characterization of auditory scene analysis in a cohort of 21 patients with clinically typical Alzheimer's disease versus age-matched healthy control subjects. We designed a novel auditory dual stream paradigm based on synthetic sound sequences to assess two key generic operations in auditory scene analysis (object segregation and grouping) in relation to simpler auditory perceptual, task and general neuropsychological factors. In order to assess neuroanatomical associations of performance on auditory scene analysis tasks, structural brain magnetic resonance imaging data from the patient cohort were analysed using voxel-based morphometry. Compared with healthy controls, patients with Alzheimer's disease had impairments of auditory scene analysis, and segregation and grouping operations were comparably affected. Auditory scene analysis impairments in Alzheimer's disease were not wholly attributable to simple auditory perceptual or task factors; however, the between-group difference relative to healthy controls was attenuated after accounting for non-verbal (visuospatial) working memory capacity. These findings demonstrate that clinically typical Alzheimer's disease is associated with a generic deficit of auditory scene analysis. Neuroanatomical associations of auditory scene analysis performance were identified in posterior cortical areas including the posterior superior temporal lobes and posterior cingulate. This work suggests a basis for understanding a class of clinical symptoms in Alzheimer's disease and for delineating cognitive mechanisms that mediate auditory scene analysis both in health and in neurodegenerative disease.

Voice processing in dementia: a neuropsychological and neuroanatomical analysis.

Voice processing in neurodegenerative disease is poorly understood. Here we undertook a systematic investigation of voice processing in a cohort of patients with clinical diagnoses representing two canonical dementia syndromes: temporal variant frontotemporal lobar degeneration (n = 14) and Alzheimer's disease (n = 22). Patient performance was compared with a healthy matched control group (n = 35). All subjects had a comprehensive neuropsychological assessment including measures of voice perception (vocal size, gender, speaker discrimination) and voice recognition (familiarity, identification, naming and cross-modal matching) and equivalent measures of face and name processing. Neuroanatomical associations of voice processing performance were assessed using voxel-based morphometry. Both disease groups showed deficits on all aspects of voice recognition and impairment was more severe in the temporal variant frontotemporal lobar degeneration group than the Alzheimer's disease group. Face and name recognition were also impaired in both disease groups and name recognition was significantly more impaired than other modalities in the temporal variant frontotemporal lobar degeneration group. The Alzheimer's disease group showed additional deficits of vocal gender perception and voice discrimination. The neuroanatomical analysis across both disease groups revealed common grey matter associations of familiarity, identification and cross-modal recognition in all modalities in the right temporal pole and anterior fusiform gyrus; while in the Alzheimer's disease group, voice discrimination was associated with grey matter in the right inferior parietal lobe. The findings suggest that impairments of voice recognition are significant in both these canonical dementia syndromes but particularly severe in temporal variant frontotemporal lobar degeneration, whereas impairments of voice perception may show relative specificity for Alzheimer's disease. The right anterior temporal lobe is likely to have a critical role in the recognition of voices and other modalities of person knowledge.

Auditory object cognition in dementia.

The cognition of nonverbal sounds in dementia has been relatively little explored. Here we undertook a systematic study of nonverbal sound processing in patient groups with canonical dementia syndromes comprising clinically diagnosed typical amnestic Alzheimer's disease (AD; n=21), progressive nonfluent aphasia (PNFA; n=5), logopenic progressive aphasia (LPA; n=7) and aphasia in association with a progranulin gene mutation (GAA; n=1), and in healthy age-matched controls (n=20). Based on a cognitive framework treating complex sounds as 'auditory objects', we designed a novel neuropsychological battery to probe auditory object cognition at early perceptual (sub-object), object representational (apperceptive) and semantic levels. All patients had assessments of peripheral hearing and general neuropsychological functions in addition to the experimental auditory battery. While a number of aspects of auditory object analysis were impaired across patient groups and were influenced by general executive (working memory) capacity, certain auditory deficits had some specificity for particular dementia syndromes. Patients with AD had a disproportionate deficit of auditory apperception but preserved timbre processing. Patients with PNFA had salient deficits of timbre and auditory semantic processing, but intact auditory size and apperceptive processing. Patients with LPA had a generalised auditory deficit that was influenced by working memory function. In contrast, the patient with GAA showed substantial preservation of auditory function, but a mild deficit of pitch direction processing and a more severe deficit of auditory apperception. The findings provide evidence for separable stages of auditory object analysis and separable profiles of impaired auditory object cognition in different dementia syndromes.

Effects of the anticonvulsant topiramate on language abilities in people with epilepsy: a cross-sectional study.

OBJECTIVES: The aim of this study was to investigate the effects of topiramate (TPM) on cognitive function, specifically language, in patients with epilepsy, and to determine whether a specifically designed neuropsychological test battery can show such effects. METHOD: Twenty patients taking TPM, 25 epilepsy controls (taking medication other than TPM) and 25 healthy controls were recruited. We used a specific neuropsychological battery, including measures of visual and verbal memory, attention, fluency and comprehension. Separate one way between group ANOVAs were performed for each neuropsychological measure. RESULTS: Bonferroni comparisons revealed that the TPM group performed significantly worse than epilepsy controls on digits forward (p<0.001), digits backward (p<0.05), controlled oral word association (COWA) (p<0.05) and token test (p<0.05). The TPM group also needed more multiple choice cues in the Boston naming test (p<0.05). CONCLUSIONS: The present study indicates that 15% of the sample tested had impaired language abilities and raises interesting questions regarding the nature of this effect. Furthermore, we have identified some short neuropsychological tasks that can be performed in routine clinical situations that can reliably identify patients who have negative linguistic effects of TPM.