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Background: Apathy is a common and early symptom in Alzheimer’s disease (AD) and is linked to poorer prognosis. Theoretical interpretations of apathy implicate alterations of connections amongst fronto-striatal and limbic regions. Objective: To test the association between presence of apathy and patterns of brain functional connectivity in patients with clinically-established AD. Methods: Seventy AD patients were included. Thirty-five patients experienced apathy as defined by the screening question of the Neuropsychiatric Inventory, and thirty-five did not. All patients agreed to undergo an MRI protocol inclusive of resting-state acquisitions. The hemodynamic-dependent signal was extracted bilaterally from five regions of interest: ventromedial prefrontal cortices, anterior cingulate cortices, dorsolateral prefrontal cortices, insulae and amygdalae. t tests were run to compare connectivity maps of apathetic and non-apathetic patients. Age, education, Mini Mental State Examination score, gray matter volumes and gray matter fractions served as covariates. Results: At a pFWE < 0.05 threshold, apathetic patients had reduced connectivity between the left insula and right superior parietal cortex. Apathetic patients had also increased connectivity between the right dorsolateral prefrontal seed and the right superior parietal cortex. Patients with apathy were significantly more likely to experience other psychiatric symptoms. Conclusion: Our findings support a role of frontal and insular connections in coordinating value-based decisions in AD. Both down-regulation and maladaptive up-regulation mechanisms appear to be at play in these regions.

Background\ud \ud A common symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is post-exertional malaise (PEM). Various brain abnormalities have been observed in patients with ME/CFS, especially in insular and limbic areas, but their link with ME/CFS symptoms is still unclear. This pilot study aimed at investigating the association between PEM in ME/CFS and changes in functional connectivity (FC) of two main networks: the salience network (SN) and the default-mode network (DMN).\ud \ud \ud Methods\ud \ud A total of 16 women, 6 with and 10 without ME/CFS, underwent clinical and MRI assessment before and after cognitive exertion. Resting-state FC maps of 7 seeds (3 for the SN and 4 for the DMN) and clinical measures of fatigue, pain and cognition were analysed with repeated-measure models. FC-symptom change associations were also investigated.\ud \ud \ud Results\ud \ud Exertion induced increases in fatigue and pain in patients with ME/CFS compared to the control group, while no changes were found in cognitive performance. At baseline, patients showed altered FC between some DMN seeds and frontal areas and stronger FC between all SN seeds and left temporal areas and the medulla. Significantly higher FC increases in patients than in controls were found only between the right insular seed and frontal and subcortical areas; these increases correlated with worsening of symptoms.\ud \ud \ud Conclusions\ud \ud Cognitive exertion can induce worsening of ME/CFS-related symptoms. These changes were here associated with strengthening of FC of the right insula with areas involved in reward processing and cognitive control.

Self-deception and impression-management comprise two types of deceptive, but generally socially acceptable behaviours, which are common in everyday life as well as being present in a number of psychiatric disorders. We sought to establish and dissociate the 'normal' brain substrates of self-deception and impression-management. Twenty healthy participants underwent fMRI scanning at 3T whilst completing the 'Balanced Inventory of Desirable Responding' test under two conditions: 'fake good', giving the most desirable impression possible and 'fake bad' giving an undesirable impression. Impression-management scores were more malleable to manipulation via 'faking' than self-deception scores. Response times to self-deception questions and 'fake bad' instructions were significantly longer than to impression-management questions and 'fake good' instructions respectively. Self-deception and impression-management manipulation and 'faking bad' were associated with activation of medial prefrontal cortex (mPFC) and left ventrolateral prefrontal cortex (vlPFC). Impression-management manipulation was additionally associated with activation of left dorsolateral prefrontal cortex and left posterior middle temporal gyrus. 'Faking bad' was additionally associated with activation of right vlPFC, left temporo-parietal junction and right cerebellum. There were no supra-threshold activations associated with 'faking good'. Our neuroimaging data suggest that manipulating self-deception and impression-management and more specifically 'faking bad' engages a common network comprising mPFC and left vlPFC. Shorter response times and lack of dissociable neural activations suggests that 'faking good', particularly when it comes to impression-management, may be our most practiced 'default' mode.

Although there is evidence that exact calculation recruits left hemisphere perisylvian language systems, recent work has shown that exact calculation can be retained despite severe damage to these networks. In this study, we sought to identify a "core" network for calculation and hence to determine the extent to which left hemisphere language areas are part of this network. We examined performance on addition and subtraction problems in two modalities: one using conventional two-digit problems that can be easily encoded into language; the other using novel shape representations. With regard to numerical problems, our results revealed increased left fronto-temporal activity in addition, and increased parietal activity in subtraction, potentially reflecting retrieval of linguistically encoded information during addition. The shape problems elicited activations of occipital, parietal and dorsal temporal regions, reflecting visual reasoning processes. A core activation common to both calculation types involved the superior parietal lobule bilaterally, right temporal sub-gyral area, and left lateralized activations in inferior parietal (BA 40), frontal (BA 6/8/32) and occipital (BA 18) regions. The large bilateral parietal activation could be attributed to visuo-spatial processing in calculation. The inferior parietal region, and particularly the left angular gyrus, was part of the core calculation network. However, given its activation in both shape and number tasks, its role is unlikely to reflect linguistic processing per se. A possibility is that it serves to integrate right hemisphere visuo-spatial and left hemisphere linguistic and executive processing in calculation.

Introduction\ud Current methods of identifying axillary node metastases in breast cancer patients are highly accurate, but are associated with several adverse events. This review evaluates the diagnostic accuracy of magnetic resonance imaging (MRI) techniques for identification of axillary metastases in early stage newly diagnosed breast cancer patients.\ud \ud Methods\ud Comprehensive searches were conducted in April 2009. Study quality was assessed. Sensitivity and specificity were meta-analysed using a bivariate random effects approach, utilising pathological diagnosis via node biopsy as the comparative gold standard.\ud \ud Results\ud Based on the highest sensitivity and specificity reported in each of the nine studies evaluating MRI (n = 307 patients), mean sensitivity was 90% (95% CI: 78–96%; range 65–100%) and mean specificity 90% (95% CI: 75–96%; range 54–100%). Across five studies evaluating ultrasmall super-paramagnetic iron oxide (USPIO)-enhanced MRI (n = 93), mean sensitivity was 98% (95% CI: 61–100%) and mean specificity 96% (95% CI: 72–100%). Across three studies of gadolinium-enhanced MRI (n = 187), mean sensitivity was 88% (95% CI: 78–94%) and mean specificity 73% (95% CI: 63–81%). In the single study of in-vivo proton MR spectroscopy (n = 27), sensitivity was 65% (95% CI: 38–86%) and specificity 100% (95% CI: 69–100%).\ud \ud Conclusions\ud USPIO-enhanced MRI showed a trend towards higher sensitivity and specificity and may make a useful addition to the current diagnostic pathway. Additional larger studies with standardised methods and standardised criteria for classifying a node as positive are needed. Current estimates of sensitivity and specificity do not support replacement of SLNB with any current MRI technology in this patient group.

Objective quantification of brain structure can aid diagnosis and therapeutic monitoring in several neuropsychiatric disorders. In this study, we aimed to compare direct and indirect quantification approaches for hippocampal formation changes in patients with mild cognitive impairment and Alzheimer's disease (AD).Twenty-one healthy volunteers (mean age: 66.2), 21 patients with mild cognitive impairment (mean age: 66.6), and 10 patients with AD (mean age: 65.1) were enrolled. All subjects underwent extensive neuropsychological testing and were imaged at 1.5T (Vision, Siemens, Germany; T1w coronal TR=4 ms, Flip=13 degrees , FOV=250 mm, Matrix=256 x 256, 128 contiguous slices, 1.8mm). Direct measurement of the hippocampal formation was performed on coronal slices using a standardized protocol, while indirect temporal horn volume (THV) was calculated using a watershed algorithm-based software package (MeVis, Germany). Manual tracing took about 30 min, semi-automated measurement less than 3 min time.Successful direct and indirect quantification was performed in all subjects. A significant volume difference was found between controls and AD patients (p0.001) with both the manual and the semi-automated approach. Group analysis showed a slight but not significant decrease of hippocampal volume and increase in temporal horn volume (THV) for subjects with mild cognitive impairment compared to volunteers (p0.07). A significant correlation (p0.001) of direct and indirect measurement was found.The presented indirect approach for hippocampus volumetry is equivalent to the direct approach and offers the advantages of observer independency, time reduction and thus usefulness for clinical routine.

Behavioural and functional anatomical responses exhibited by humans support the hypothesis that deception involves the prefrontal executive. Functional neuroimaging studies have demonstrated that ventrolateral prefrontal cortex (among other areas) is activated during lying, compared with telling the truth. However, despite some consistencies discernible across studies, problems remain concerning experimental validity, e.g., the expediencies of experimenter-sanctioned cued-deception (i.e., subjects being told when to lie); such 'lies' may not have comprised adequate proxies for 'real-life' deception. In this experiment, we attempted to address such confounding issues by designing an fMRI paradigm in which subjects chose when to lie (thereby minimising cue-dependency), using spoken words, concerning intimate material, which they regarded as 'embarrassing'; and where further control conditions required them to 'comply' with their examiners or to 'defy' them (by withholding pre-specified responses). The main effect of lying revealed significant activation of ventrolateral prefrontal cortices. These results replicate and extend our previous findings to those circumstances under which subjects are allowed to choose when to deceive.

The purpose of this study is to describe our initial experience of imaging adults with localisation-related epilepsy using MR imaging at 3.0T. We discuss the findings in the context of the recently released NICE guidelines that provide detailed advice on imaging people with epilepsy in the UK. 120 consecutive people over the age of 16 years with localisation-related epilepsy were referred for clinical MR examinations from a regional neuroscience centre in England. None of the people had had MR examinations prior to the present study. High resolution MR imaging was performed taking advantage of the high field strength and high performance gradients of the system. Two experienced neuroradiologists reported on the examinations independently and the presence and type of pathology was recorded. There was complete agreement between the two reporters in all 120 cases. The overall frequency of abnormalities shown by MR was 31/120 (26%) and the commonest abnormality shown was mesial temporal sclerosis found in 10/120 (8%). Tumours were shown in 4/120, all of which appeared low grade as judged by imaging criteria. Epilepsy is the commonest neurological condition and demands a significant resource in order to provide good care for sufferers. Recent guidelines published in the UK have suggested that the majority of people with epilepsy should receive brain MR as part of their routine assessment. Our work shows that using the most sophisticated MR imaging in a highly selected population there is a modest pick-up rate of brain abnormalities. If a widespread epilepsy-imaging programme is started the detection rate is likely to be much lower. Although MR is acknowledged to be a reliable way of detecting pathology in people with epilepsy there is a dearth of information studying the health economics of imaging epilepsy in relation to patient management and outcomes.

In schizophrenia, auditory verbal hallucinations (AVHs) are likely to be perceived as gender-specific. Given that functional neuro-imaging correlates of AVHs involve multiple brain regions principally including auditory cortex, it is likely that those brain regions responsible for attribution of gender to speech are invoked during AVHs. We used functional magnetic resonance imaging (fMRI) and a paradigm utilising 'gender-apparent' (unaltered) and 'gender-ambiguous' (pitch-scaled) male and female voice stimuli to test the hypothesis that male and female voices activate distinct brain areas during gender attribution. The perception of female voices, when compared with male voices, affected greater activation of the right anterior superior temporal gyrus, near the superior temporal sulcus. Similarly, male voice perception activated the mesio-parietal precuneus area. These different gender associations could not be explained by either simple pitch perception or behavioural response because the activations that we observed were conjointly activated by both 'gender-apparent' and 'gender-ambiguous' voices. The results of this study demonstrate that, in the male brain, the perception of male and female voices activates distinct brain regions.

AIMS: To corroborate the findings of in utero magnetic resonance imaging (MRI) with autopsy and post-mortem MRI in cases of known or suspected central nervous system (CNS) abnormalities on ultrasound and to compare the diagnostic accuracy of ante-natal ultrasound and in utero MRI. METHODS: Twelve pregnant women, whose foetuses had suspected central nervous system abnormalities underwent in utero MRI. The foetuses were imaged using MRi before autopsy. The data were used to evaluate the diagnostic accuracy of in utero MRI when compared with a reference standard of autopsy and post-mortem MRI in 10 cases and post-mortem MRI alone in two cases. RESULTS: The diagnostic accuracy of antenatal ultrasound and in utero MRI in correctly characterizing brain and spine abnormalities were 42 and 100%, respectively. CONCLUSION: In utero MRI provides a useful adjuvant to antenatal ultrasound when assessing CNS abnormalities by providing more accurate anatomical information. Post-mortem MRI assists the diagnosis of macroscopic structural abnormalities.

A parameter, χ 2 p , based on the fitting error was introduced as a measure of reliability of DT-MRI data, and its properties were investigated in simulations and human brain data. Its comparison with the classic χ 2 revealed its sensitivity to both the goodness of fit and the pixel signal-to-noise-ratio (SNR), unlike the classic χ 2 , which is sensitive only to the goodness of fit. The new parameter was thus able to separate effectively pixels with coherent signals (having small fitting error and/or high SNR) from those with random signals (having inconsistent fitting and/or low SNR). A practical advantage of χ 2 p over the classic χ 2 was that χ 2 p is quantified directly from the data of each pixel, without requiring accurate estimation of data-dependent parameters (such as noise variance), which often makes application of the classic χ 2 problematic. Analytical approximations of χ 2 p enabled an objective (data-independent) and automated calculation of a threshold value, used for internal scaling of the χ 2 p map. Apart from assessing data reliability on a pixel-by-pixel basis, χ 2 p was used to develop an objective and generic methodology for the exclusion of pixels with unreliable DT information by discarding pixels with χ 2 p values exceeding the threshold. Pixels corresponding to very low SNR, and poorly fitted cerebrospinal fluid and surrounding brain tissue, had increased χ 2 p values and were successfully excluded, providing DT anisotropy maps free from artifactual anisotropic appearance.

This paper introduces the concept of imaging with stepped magnetic fields within the main B 0 field. The resonance frequency within each step is separated from the next by an amount greater than the imaging bandwidth. Each step thus gives rise to a separate imaging region enabling simultaneous imaging over multiple slices without aliasing. The auxiliary magnetic field regions are produced by coil inserts. The principle is illustrated using simple coil designs which introduce up to two steps into the main B 0 field. Phantoms placed in each uniform region were successfully imaged simultaneously with no aliasing.

AIM: To study the proton MR spectroscopic findings in Creutzfeldt--Jakob disease (CJD) (sporadic and variant). MATERIALS AND METHODS: MR imaging and proton MR spectra were acquired in two patients with sporadic CJD (biopsy proven) and one patient with variant CJD. RESULTS: The two patients with sporadic CJD demonstrated MR signal change within the basal ganglia and thalami and reduced N-acetylaspartate (NAA):creatine ratios. The patient with variant CJD showed characteristic signal change within the pulvinar of the thalami and a markedly reduced N-acetylaspartate:creatine ratio. CONCLUSION: All three patients with CJD demonstrated evidence of reduced N-acetylaspartate: creatine ratios on MR spectroscopy. These changes imply that neuronal loss and/or dysfunction is a consistent finding in established CJD. Pandya H. G., et al (2003) Clinical Radiology58, 148--153

We introduce two independent component analysis (ICA) methods, spatiotemporal ICA (stICA) and skew-ICA, and demonstrate the utility of these methods in analyzing synthetic and event-related fMRI data. First, stICA simultaneously maximizes statistical independence over both time and space. This contrasts with conventional ICA methods, which maximize independence either over time only or over space only; these methods often yield physically improbable solutions. Second, skew-ICA is based on the assumption that images have skewed probability density functions (pdfs), an assumption consistent with spatially localized regions of activity. In contrast, conventional ICA is based on the physiologically unrealistic assumption that images have symmetric pdfs. We combine stICA and skew-ICA, to form skew-stICA, and use it to analyze synthetic data and data from an event-related, left-right visual hemifield fMRI experiment. Results obtained with skew-stICA are superior to those of principal component analysis, spatial ICA (sICA), temporal ICA, stICA, and skew-sICA. We argue that skew-stICA works because it is based on physically realistic assumptions and that the potential of ICA can only be realized if such prior knowledge is incorporated into ICA methods.

Two of the recognized cranial MRI findings in children with neurofibromatosis type 1 (NF1) are neurofibromatosis bright objects (NBO) and brain glioma. Their differential diagnosis can be problematic. This study aimed to determine the features of these abnormalities on short echo-time in-vivo proton magnetic resonance spectroscopy. Twenty children under the age of 16 with NF1 were studied. A single voxel, short echo-time technique (TE = 20 ms; TR = 5000 ms) was used to obtain proton spectra of typical NBO and any regions suggestive of atypical bright objects or tumor. Nine children without neurofibromatosis with no structural brain abnormality acted as aged-matched comparisons. A semi-quantitative analysis indicated significant increase in choline and myo-inisitol in tumors compared to typical NBO (p < 0.05) and compared to controls (p < 0.05); reduction in the levels of N-acetyl moieties in NBO compared to controls (p < 0.05); reduction in N-acetyl in tumors compared to controls (p < 0.001); and reduction in glutamate/glutamine in tumors compared to controls (p < 0.05). This cross-sectional data suggests that proton spectroscopy can aid differentiating between NBO and brain (non-optic/hypothalamic) glioma. Typical NBO have different short echo-time spectroscopic appearances compared to normal brain.

Stroke is a clinical syndrome of a rapidly developing focal neurological deficit that may be classified for practical purposes into ischaemic and haemorrhagic. The role of imaging is to exclude mimics of ischaemic stroke or intracranial haemorrhage and confirm the presence of an ischaemic stroke. Computed tomography (CT) remains the investigation of choice to exclude acute intracranial haemorrhage but diffusion weighted magnetic resonance (MR) has proved to be a sensitive method of detecting early ischaemic infarction. Perfusion weighted MR allows further assessment at the same examination that could help guide the clinician in the risk/benefit analysis of treatment with thrombolytics or neuroprotective agents under evaluation. This can also be achieved with CT. This review article discusses the imaging of ischaemic stroke, relating the pathophysiology of stroke to it. It deals separately in more detail with these newer MR techniques.

AIM: To compare the accuracy of ultrasound and two magnetic resonance (MR) angiographic techniques with catheter angiography in assessing atherosclerosis at the carotid bifurcation. MATERIALS AND METHODS: Forty patients with symptomatic carotid stenosis were studied by Doppler ultrasound, time-of-flight MR angiography, contrast-enhanced MR angiography and conventional catheter angiography. The degree of stenosis found on ultrasound and MR angiography was compared with the results of catheter angiography. Four different assessment methods were conducted for the MR angiographic data. Kappa, sensitivity and specificity (with confidence intervals) values were calculated for the US and MR angiography results compared to catheter angiography. RESULTS: Catheter angiography showed 12 internal carotid artery occlusions (15%), 34 severe (44%), 12 moderate (15%) and 20 mild stenoses (26%), using NASCET criteria. Ultrasound showed 65% sensitivity and 95% specificity in detecting surgically amenable lesions, whilst the MR angiographic techniques had sensitivities varying from 82–100%, and specificities from 95–100%. A moderate kappa value was calculated for the US data, whilst all MR techniques were found to show very good agreement with catheter angiography. CONCLUSION: This data suggests that MR angiography is more accurate than Doppler ultrasound in defining surgical lesions and has comparable accuracy to catheter angiography. The use of contrast-enhanced MR angiography is useful in certain situations but is not essential in all cases.Johnson, M. B., (2000). Clinical Radiology 55 , 912–920.

Recirculating and detached flow patterns close to the carotid bifurcation are thought to play an important role in the development of carotid stenoses by promoting atherosclerosis. The aim of this study was to investigate a flow regime with strong transient characteristics, including vortex shedding and transport to develop methodologies appropriate to the analysis of carotid stenoses. The existence of a regular periodic vortex street behind a cylindrical flow obstruction was predicted and analysed in detail by Theodore van Karman in the early 20th century. This model was chosen in our study for both ease of phantom construction and of theoretical modelling using finite element computational fluid dynamics (CFD). The results of the theoretical calculations have been compared with two methods of flow visualization—laser sheet imaging and real-time echo planar magnitude MR imaging. Flow was investigated over a range of Reynold’s number from 40 through 400 through which vortex shedding is predicted. Good overall agreement was obtained between the theoretical (16 mm-CFD) and experimental (16 ± 2mm-Laser, 17 ± 2mm-MRI) estimates of the Karman Vortex street wavelength for a Reynolds number of 200.

Sanfilippo syndrome is an autosomal recessive lysosomal storage disorder that leads to a deficiency of enzymes involved in the degradation of mucopolysaccharides. This results in an excessive accumulation of mucopolysaccharides in cells of the body. This accumulate can cause progressive damage to surrounding tissue. Brain imaging classically demonstrates two major patterns: (a) white matter high T2 signal abnormality and (b) prominent cystic lesions and perivascular spaces. The cerebellum, medulla and pons tend to be spared. The role of proton MR spectroscopy (H-MRS) is less clear cut; but it may complement MR imaging in diagnosis and therapeutic monitoring of the disease. We report the H-MRS findings of a child with Sanfilippo syndrome, which confirms the characteristic pattern described in the limited number of previously reported cases.

Brain iron deposition was assessed at 1.5 T in the caudate nucleus, globus pallidus and frontal and parieto-occipital white matter in 28 human immunodeficiency virus (HIV)-infected patients and 15 control subjects with a new Partially Refocussed Interleaved Multi-Echo sequence by measuring 1/T2, 1/T2* and 1/T2' (i.e., R2, R2* and R2'). There were significant differences in the R2 and R2* of the caudate nucleus (p < 0.0001 and p < 0.05) and the R2, R2* and R2' of the globus pallidus (p < 0.01, p < 0.005 and p < 0.05) in HIV-infected patients compared to control subjects. There was a trend for higher values of R2, R2* and R2' in the globus pallidus and caudate nucleus in HIV-infected patients with later stage HIV disease. These results suggest that there is greater iron deposition in the basal ganglia of HIV-infected patients compared with control subjects, with a predilection for the globus pallidus. The relationship between iron deposition in the brain and various parameters of severity of HIV infection remains uncertain.

White matter change occurs in human immunodeficiency virus (HIV) encephalopathy, which may be difficult to assess subjectively especially in the early stages of disease. This study applies a quantitative approach to the assessment of this finding. Sixty-three HIV seropositive subjects, 47 seronegative blood donors and 17 seronegative homosexual men underwent axial T2 weighted MRI of the brain at 1.5T. Quantitative analysis was performed by obtaining the pixel contrast between parieto-occipital white matter and head of caudate grey matter (Cwg). Highest values of Cwg were found in a subgroup of subjects with AIDS who had diffuse/patchy white matter abnormalities and atrophy on qualitative image assessment. Statistically significant differences were found in Cwg between subjects with high (or = 200 x 10(6)/I) and low (200 x 10(6)/I) CD4 lymphocyte counts (P0.05) and between subjects with and without HIV-1 associated cognitive/motor complex (P0.05). This technique provides an objective measure of diffuse HIV-related parenchymal abnormality seen on T2 weighted MRI.

Sinusitis poses a difficult clinical challenge in the management of patients with AIDS because of high rates of relapse and the association with unusual pathogens. To determine the prevalence and severity of sinus disease in this group we prospectively analysed the condition of the paranasal sinuses shown on cranial MR scans of 156 patients referred for the investigation of suspected intracranial pathologies. These included 104 HIV seropositive patients, including 93 with an AIDS-defining diagnosis (CDC IV). Forty-two scans were performed on age-matched controls. The scans were timed to control for seasonal variations in sinus disease and were interpreted by two radiologists who were blinded to the clinical and serological status of the patients. Severe mucosal disease (more than one sinus showing > 75% obliteration) or moderate mucosal disease (only one sinus showing > 75% obliteration) was seen in 15.1% (14/93) patients with AIDS and none of the 42 controls (chi 2 = 6.73, P < 0.01). The mean maximum mucosal thickness in patients with AIDS was significantly greater than the control group (P < 0.001) and also significantly greater than in seropositive patients who had not had an AIDS-defining diagnosis (CDC II/III) (P = 0.006). Paranasal sinus mucosal abnormalities seen on MRI are greater in prevalence and severity in patients with AIDS and about one in seven would be expected to have at least one sinus largely obliterated.

Background Prevalence of neurological dysfunction in a prospective cohort of patients newly diagnosed with coeliac disease is yet to be determined. The spectrum of neurological deficit in patients with this disease remains unclear. We aimed to establish the prevalence of neurological deficit in patients newly diagnosed with coeliac disease and to compare the clinicoradiological features of this group with patients presenting with neurological changes that eventually led to diagnosis of the disorder. Methods Patients with newly diagnosed coeliac disease recruited from a tertiary referral gastrointestinal clinic at the Sheffield Teaching Hospitals NHS Foundation Trust were prospectively reviewed by a neurologist and underwent MRI of the brain. Clinicoradiological features of patients who presented with neurological dysfunction to a tertiary referral neurological clinic and who were subsequently diagnosed with coeliac disease were retrospectively reviewed. MRI biomarkers—cerebellar volume (percentage ratio of cerebellar volume to total intracranial volume [%CV:TIV]); N-acetylaspartate to creatine ratio (NAA/Cr), a marker of neuronal health, measured with cerebellar proton MR spectroscopy; and voxel-based morphometry (VBM)—were analysed. Data were also compared with those of healthy volunteers who underwent the same MRI protocol and who were recruited from the local area. Regional ethics committee approved the study and all participants gave informed consent. Findings 30 patients (mean age 47 years, SD 16, range 23–77; 12 men) with newly diagnosed coeliac disease were recruited. 20 patients (61 years, 10, 42–74, nine men) diagnosed with coeliac disease after initially presenting with neurological dysfunction (neurological dysfunction group) were reviewed. MRI data were obtained from a register of 55 healthy volunteers (41 years, 15, 20–77; 32 men). 11 patients (37%) with newly diagnosed coeliac disease had neurological deficits on clinical examination, ten with mild gait ataxia and one with peripheral neuropathy. 16 patients (80%) in the neurological dysfunction group had gait ataxia (nine mild, six moderate, one severe); four patients had peripheral sensory neuropathy. %CV:TIV and NAA/Cr were significantly reduced in the neurological dysfunction group compared with patients with newly diagnosed disease (mean %CV:TIV 7·5 [SD 1·5] vs 8·5 [0·8], 95% CI 0·24–1·76; p=0·01 and NAA/Cr 0·85 [0·13] vs 0·95 [0·07], 0·04–0·17; p=0·004). %CV:TIV and NAA/Cr were also significantly lower in the neurological dysfunction group than in healthy volunteers (mean %CV:TIV 7·5 [SD 1·5] vs 8·4 [1·2], 95% CI 0·05–1·83; p=0·039 and NAA/Cr 0·85 [0·13] vs 0·98 [0·09], 0·05–0·20; p=0·001). There was no significant difference in %CV:TIV or NAA/Cr between patients newly diagnosed with coeliac disease and healthy volunteers. Patients in the neurological dysfunction group showed multiple regions of reduced grey matter density, especially of the cerebellum but also involving supratentorial regions (p Interpretation Our results might not be generalisable because data were obtained from a tertiary referral centre. Moreover, analysis of the neurological dysfunction subgroup was retrospective. Nonetheless, to our knowledge this is the first study to attempt to provide a prevalence of neurological dysfunction prospectively in patients with coeliac disease while also examining MRI biomarkers of brain dysfunction. This study seems to show that a significant proportion of patients presenting with gastrointestinal symptoms who are diagnosed with coeliac disease already have some neurological dysfunction. The group of patients that present with neurological dysfunction are more severely affected. Serological testing for the disease should be incorporated into the investigation of patients with unexplained neurological symptoms. Increased awareness of the spectrum of neurological dysfunction in coeliac disease and close collaboration between neurologists and gastroenterologists might increase detection and prevent unnecessary delay to dietary treatment, which could lead to permanent neurological disability. Funding Coeliac UK, Bardhan Research & Education Trust.

The pathogenesis of diabetic distal symmetrical polyneuropathy (DSP) is poorly understood but there is some evidence that the disease process might extend beyond peripheral nerves. We used magnetic-resonance imaging to measure spinal-cord cross-sectional area in diabetic patients with and without DSP and in healthy controls. There were significant differences in cord area between the groups at C4/5 and T3/4 (p=0.004 and p=0.033, respectively), with a smaller cord area in those with DSP compared with controls (p=0.001 and p=0.016 for C4/5 and T3/4, respectively). These results indicate that DSP is not simply a disease of the peripheral nerve and that there is substantial involvement of the spinal cord.