Stuart Currie

Diffusion-weighted MRI determined cerebral embolic infarction following transcatheter aortic valve implantation: assessment of predictive risk factors and the relationship to subsequent health status

Background ‘Silent’ cerebral infarction and stroke are complications of transcatheter aortic valve implantation (TAVI). Objective To assess the occurrence of cerebral infarction, identify predictive risk factors and examine the impact on patient health-related quality of life (HRQoL). Methods Cerebral diffusion weighted MRI of 31 patients with aortic stenosis undergoing CoreValve TAVI was carried out. HRQoL was assessed at baseline and at 30 days by SF-12v2 and EQ5D questionnaires. Results New cerebral infarcts occurred in 24/31 patients (77%) and stroke in 2 (6%). Stroke was associated with a greater number and volume of cerebral infarcts. Age (r=0.37, p=0.042), severity of atheroma (arch and descending aorta; r=0.91, p<0.001, r=0.69, p=0.001, respectively) and catheterisation time (r=0.45, p=0.02) were predictors of the number of new cerebral infarcts. HRQoL improved overall: SF-12v2 physical component summary increased significantly (32.4±6.2 vs 36.5±7.2; p=0.03) with no significant change in mental component summary (43.5±11.7 vs 43.1±14.3; p=0.85). The EQ5D score and Visual Analogue Scale showed no significant change (0.56±0.26 vs 0.59±0.31; p=0.70, and 54.2±19 vs 58.2±24; p=0.43). Conclusion Multiple small cerebral infarcts occurred in 77% of patients with TAVI. The majority of infarcts were ‘silent’ with clinical stroke being associated with a both higher infarct number and volume. Increased age and the severity of aortic arch atheroma were independent risk factors for the development of new cerebral infarcts. Overall HRQoL improved and there was no association between the number of new cerebral infarcts and altered health status.

Imaging assessment of traumatic brain injury

Traumatic brain injury (TBI) constitutes injury that occurs to the brain as a result of trauma. It should be appreciated as a heterogeneous, dynamic pathophysiological process that starts from the moment of impact and continues over time with sequelae potentially seen many years after the initial event. Primary traumatic brain lesions that may occur at the moment of impact include contusions, haematomas, parenchymal fractures and diffuse axonal injury. The presence of extra-axial intracranial lesions such as epidural and subdural haematomas and subarachnoid haemorrhage must be anticipated as they may contribute greatly to secondary brain insult by provoking brain herniation syndromes, cranial nerve deficits, oedema and ischaemia and infarction. Imaging is fundamental to the management of patients with TBI. CT remains the imaging modality of choice for initial assessment due to its ease of access, rapid acquisition and for its sensitivity for detection of acute haemorrhagic lesions for surgical intervention. MRI is typically reserved for the detection of lesions that may explain clinical symptoms that remain unresolved despite initial CT. This is especially apparent in the setting of diffuse axonal injury, which is poorly discerned on CT. Use of particular MRI sequences may increase the sensitivity of detecting such lesions: diffusion-weighted imaging defining acute infarction, susceptibility-weighted imaging affording exquisite data on microhaemorrhage. Additional advanced MRI techniques such as diffusion tensor imaging and functional MRI may provide important information regarding coexistent structural and functional brain damage. Gaining robust prognostic information for patients following TBI remains a challenge. Advanced MRI sequences are showing potential for biomarkers of disease, but this largely remains at the research level. Various global collaborative research groups have been established in an effort to combine imaging data with clinical and epidemiological information to provide much needed evidence for improvement in the characterisation and classification of TBI and in the identity of the most effective clinical care for this patient cohort. However, analysis of collaborative imaging data is challenging: the diverse spectrum of image acquisition and postprocessing limits reproducibility, and there is a requirement for a robust quality assurance initiative. Future clinical use of advanced neuroimaging should ensure standardised approaches to image acquisition and analysis, which can be used at the individual level, with the expectation that future neuroimaging advances, personalised to the patient, may improve prognostic accuracy and facilitate the development of new therapies.

Magnetic resonance spectroscopy of the brain

Proton magnetic resonance (MR) spectroscopy of the brain is a non-invasive, in vivo technique that allows investigation into regional chemical environments. Its complementary use with MR imaging sequences provides valuable insights into brain tumour characteristics, progression and response to treatment. Additionally, its sensitivity to brain dysfunction in the presence of apparently normal structural imaging has galvanised interest in its use as a biomarker of neurodegenerative disorders such as Alzheimers disease. Accordingly, its integration into clinical imaging protocols within many neuroscience centres throughout the world is increasing. This growing attention is encouraging but if the potential of MR spectroscopy is to be realised, fundamental questions need to be addressed, such as reproducibility of the technique and the biochemistry that underpins the neurometabolites measured. Failure to resolve these issues will continue to hinder the extent and accuracy of conclusions that can be drawn from its data. In this review we discuss the issues regarding MR spectroscopy in the brain with particular attention paid to its technique. Key examples of current clinical applications are provided and future directions are discussed.

Should we be 'nervous' about coeliac disease? Brain abnormalities in patients with coeliac disease referred for neurological opinion

Objectives To examine the extent of brain abnormality in patients with coeliac disease referred for neurological opinion and evaluate MR imaging sequences as biomarkers for neurological dysfunction, given the lack of readily available serological markers of neurological disease in this cohort. Methods Retrospective examination of a consecutive cohort of patients (n=33, mean age=44±13 years (range 19–64)) with biopsy proven coeliac disease referred for neurological opinion. Patients were divided into subgroups based on their primary neurological complaint (balance disturbance, headache and sensory loss). 3T MR was used to evaluate differences in brain grey matter density, cerebellar volume, cerebellar neurochemistry and white matter abnormalities (WMAs) between subjects and controls. Results Cerebellar volume was significantly less in the patient group than in controls (6.9±0.7% vs 7.4±0.9% of total intracranial volume, p<0.05). Significantly less grey matter density was found in multiple brain regions, both above and below the tentorium cerebelli, than in controls (p<0.05). 12 (36%) patients demonstrated WMAs unexpected for the patients age, with the highest incidence occurring in the headache subgroup. This subgroup averaged almost twice the number of WMAs per MR imaging than the subgroup with balance disturbance and six times more than the subgroup with sensory loss. Conclusion Patients with established coeliac disease referred for neurological opinion show significant brain abnormality on MR imaging. MR imaging may provide valuable biomarkers of disease in this patient cohort.

MRI characteristics of tuberculous spondylitis

Spondylitis is the most common osseous manifestation of Mycobacterium tuberculosis infection. Although treatable, it continues to cause significant mortality and morbidity. Early diagnosis through familiarity with its imaging characteristics is essential to permit rapid treatment and prevent potential life-limiting consequences. In this review, we demonstrate the key magnetic resonance imaging features of this disease.

Consensus Paper: Radiological Biomarkers of Cerebellar Diseases

Hereditary and sporadic cerebellar ataxias represent a vast and still growing group of diseases whose diagnosis and differentiation cannot only rely on clinical evaluation. Brain imaging including magnetic resonance (MR) and nuclear medicine techniques allows for characterization of structural and functional abnormalities underlying symptomatic ataxias. These methods thus constitute a potential source of radiological biomarkers, which could be used to identify these diseases and differentiate subgroups of them, and to assess their severity and their evolution. Such biomarkers mainly comprise qualitative and quantitative data obtained from MR including proton spectroscopy, diffusion imaging, tractography, voxel-based morphometry, functional imaging during task execution or in a resting state, and from SPETC and PET with several radiotracers. In the current article, we aim to illustrate briefly some applications of these neuroimaging tools to evaluation of cerebellar disorders such as inherited cerebellar ataxia, fetal developmental malformations, and immune-mediated cerebellar diseases and of neurodegenerative or early-developing diseases, such as dementia and autism in which cerebellar involvement is an emerging feature. Although these radiological biomarkers appear promising and helpful to better understand ataxia-related anatomical and physiological impairments, to date, very few of them have turned out to be specific for a given ataxia with atrophy of the cerebellar system being the main and the most usual alteration being observed. Consequently, much remains to be done to establish sensitivity, specificity, and reproducibility of available MR and nuclear medicine features as diagnostic, progression and surrogate biomarkers in clinical routine.

Endovascular treatment of intracranial aneurysms: review of current practice

Subarachnoid haemorrhage remains a major cause of morbidity and mortality throughout the world. Of those suffering the condition, 15% are known to die before they reach hospital and half of all patients die within 1 month of presentation. Of those patients who survive the initial 30 days, just under half are believed to remain dependent for their normal activities of daily living. In the vast majority of cases, SAH results from the rupture of an intracranial aneurysm. After patient stabilisation, primary treatment is focused on the prevention of re-bleeding. Until recently, this exclusively involved the surgical clipping of the ruptured aneurysm via a craniotomy. The early 1990s, with the introduction of aneurysmal coiling via endovascular intervention, heralded the dawn of a new treatment option. Presently, endovascular therapy largely supersedes surgical intervention in the management of intracranial aneurysms in the developed world. Moreover, with the emergence of new technologies and approaches for the treatment of aneurysms, the field of neurovascular intervention is only likely to expand further. However, due to its relative infancy, unanswered questions regarding long term endovascular outcome remain. This is particularly pertinent to newer techniques of embolisation for which data on complete aneurysmal occlusion rates are limited. Thus, to understand fully the capability and limitations of this treatment, further well constructed randomised controlled trials are a necessity.

Understanding MRI: basic MR physics for physicians

More frequently hospital clinicians are reviewing images from MR studies of their patients before seeking formal radiological opinion. This practice is driven by a multitude of factors, including an increased demand placed on hospital services, the wide availability of the picture archiving and communication system, time pressures for patient treatment (eg, in the management of acute stroke) and an inherent desire for the clinician to learn. Knowledge of the basic physical principles behind MRI is essential for correct image interpretation. This article, written for the general hospital physician, describes the basic physics of MRI taking into account the machinery, contrast weighting, spin- and gradient-echo techniques and pertinent safety issues. Examples provided are primarily referenced to neuroradiology reflecting the subspecialty for which MR currently has the greatest clinical application.

Magnetic Resonance Imaging Biomarkers in Patients with Progressive Ataxia: Current Status and Future Direction

A diagnostic challenge commonly encountered in neurology is that of an adult patient presenting with ataxia. The differential is vast and clinical assessment alone may not be sufficient due to considerable overlap between different causes of ataxia. Magnetic resonance (MR)-based biomarkers such as voxel-based morphometry, MR spectroscopy, diffusion-weighted and diffusion-tensor imaging and functional MR imaging are gaining great attention for their potential as indicators of disease. A number of studies have reported correlation with clinical severity and underlying pathophysiology, and in some cases, MR imaging has been shown to allow differentiation of conditions causing ataxia. However, despite recent advances, their sensitivity and specificity vary. In addition, questions remain over their validity and reproducibility, especially when applied in routine clinical practice. This article extensively reviews the current literature regarding MR-based biomarkers for the patient with predominantly adult-onset ataxia. Imaging features characteristic of a particular ataxia are provided and features differentiating ataxia groups and subgroups are discussed. Finally, discussion will turn to the feasibility of applying these biomarkers in routine clinical practice.

Progressive ataxia with palatal tremor due to gluten sensitivity.

Palatal tremor is characterized by involuntary and continuous rhythmic movement of the soft palate. It is divided into symptomatic palatal tremor (SPT) and essential palatal tremor (EPT). In EPT the patient complains of ear discomfort and a clicking noise generated by the contraction of the tensor veli palatini muscle, responsible for opening of the eustachian tube. In SPT there is contraction of the levator veli palatini muscle, but the patient is usually unaware of it. A subgroup of SPT is associated with ataxia, known as progressive ataxia with palatal tremor (PAPT). SPT and PAPT can result from a lesion in the Mollaret triangle (inferior olive, red nucleus, contralateral dentate nucleus). In some cases no lesion is demonstrable, and the etiology remains obscure. We describe here a patient with PAPT due to gluten sensitivity. A 66-year-old woman with a history of rheumatoid arthritis was first referred to neurology 24 years ago with a 1-year history of slurred speech and unsteadiness of gait. Examination revealed gait ataxia, slurred speech, and palatal tremor. There was no family history of ataxia. Investigations including CSF analysis and genetic, paraneoplastic antibody, and vitamin E testing were negative. MRI demonstrated cerebellar atrophy involving both the vermis and the hemispheres and revealed hypertrophic inferior olives without any structural lesion. Antigliadin antibodies were positive, and her HLA was DQ2 in keeping with gluten sensitivity. She refused a duodenal biopsy but commenced a gluten-free diet. During the ensuing years she remained clinically stable from the ataxia point of view. The patient and her husband spontaneously reported improvement of the palatal tremor 2 years after the introduction of the gluten-free diet. Repeat MR imaging (Fig. 1) showed