Neuroimaging of epilepsy: lesions, networks, oscillations

While analysis and interpretation of structural epileptogenic lesion is an essential task for the neuroradiologist in clinical practice, a substantial body of epilepsy research has shown that focal lesions influence brain areas beyond the epileptogenic lesion, across ensembles of functionally and anatomically connected brain areas. In this review article, we aim to provide an overview about altered network compositions in epilepsy, as measured with current advanced neuroimaging techniques to characterize the initiation and spread of epileptic activity in the brain with multimodal noninvasive imaging techniques. We focus on resting-state functional magnetic resonance imaging (MRI) and simultaneous electroencephalography/fMRI, and oppose the findings in idiopathic generalized versus focal epilepsies. These data indicate that circumscribed epileptogenic lesions can have extended effects on many brain systems. Although epileptic seizures may involve various brain areas, seizure activity does not spread diffusely throughout the brain but propagates along specific anatomic pathways that characterize the underlying epilepsy syndrome. Such a functionally oriented approach may help to better understand a range of clinical phenomena such as the type of cognitive impairment, the development of pharmacoresistance, the propagation pathways of seizures, or the success of epilepsy surgery.

Gadoxetate uptake as a possible marker of hepatocyte damage after liver resection-preliminary data

AIM: To determine the feasibility of evaluating surgically induced hepatocyte damage using gadoxetate disodium (Gd-EOB-DTPA) as a marker for viable hepatocytes at magnetic resonance imaging (MRI) after liver resection. MATERIAL AND METHODS: Fifteen patients were prospectively enrolled in this institutional review board-approved study prior to elective liver resection after informed consent. Three Tesla MRI was performed 3-7 days after surgery. Three-dimensional (3D) T1-weighted (W) volumetric interpolated breath-hold gradient echo (VIBE) sequences covering the liver were acquired before and 20 min after Gd-EOB-DTPA administration. The signal-to-noise ratio (SNR) was used to compare the uptake of Gd-EOB-DTPA in healthy liver tissue and in liver tissue adjacent to the resection border applying paired Student's t-test. Correlations with potential influencing factors (blood loss, duration of intervention, age, pre-existing liver diseases, postoperative change of resection surface) were calculated using Pearson's correlation coefficient. RESULTS: Before Gd-EOB-DTPA administration the SNR did not differ significantly (p = 0.052) between healthy liver tissue adjacent to untouched liver borders [59.55 ± 25.46 (SD)] and the liver tissue compartment close to the resection surface (63.31 ± 27.24). During the hepatocyte-specific phase, the surgical site showed a significantly (p = 0.04) lower SNR (69.44 ± 24.23) compared to the healthy site (78.45 ± 27.71). Dynamic analyses revealed a significantly lower increase (p = 0.008) in signal intensity in the healthy tissue compared to the resection border compartment. CONCLUSION: EOB-DTPA-enhanced MRI may have the potential to be an effective non-invasive tool for detecting hepatocyte damage after liver resection.

Grey matter volumetric changes related to recovery from hand paresis after cortical sensorimotor stroke

Preclinical studies using animal models have shown that grey matter plasticity in both perilesional and distant neural networks contributes to behavioural recovery of sensorimotor functions after ischaemic cortical stroke. Whether such morphological changes can be detected after human cortical stroke is not yet known, but this would be essential to better understand post-stroke brain architecture and its impact on recovery. Using serial behavioural and high-resolution magnetic resonance imaging (MRI) measurements, we tracked recovery of dexterous hand function in 28 patients with ischaemic stroke involving the primary sensorimotor cortices. We were able to classify three recovery subgroups (fast, slow, and poor) using response feature analysis of individual recovery curves. To detect areas with significant longitudinal grey matter volume (GMV) change, we performed tensor-based morphometry of MRI data acquired in the subacute phase, i.e. after the stage compromised by acute oedema and inflammation. We found significant GMV expansion in the perilesional premotor cortex, ipsilesional mediodorsal thalamus, and caudate nucleus, and GMV contraction in the contralesional cerebellum. According to an interaction model, patients with fast recovery had more perilesional than subcortical expansion, whereas the contrary was true for patients with impaired recovery. Also, there were significant voxel-wise correlations between motor performance and ipsilesional GMV contraction in the posterior parietal lobes and expansion in dorsolateral prefrontal cortex. In sum, perilesional GMV expansion is associated with successful recovery after cortical stroke, possibly reflecting the restructuring of local cortical networks. Distant changes within the prefrontal-striato-thalamic network are related to impaired recovery, probably indicating higher demands on cognitive control of motor behaviour.

Transient loss of consciousness and syncope

Syncope describes a sudden and brief transient loss of consciousness (TLOC) with postural failure due to cerebral global hypoperfusion. The term TLOC is used when the cause is either unrelated to cerebral hypoperfusion or is unknown. The most common causes of syncopal TLOC include: (1) cardiogenic syncope (cardiac arrhythmias, structural cardiac diseases, others); (2) orthostatic hypotension (due to drugs, hypovolemia, primary or secondary autonomic failure, others); (3) neurally mediated syncope (cardioinhibitory, vasodepressor, and mixed forms). Rarely neurologic disorders (such as epilepsy, transient ischemic attacks, and the subclavian steal syndrome) can lead to cerebal hypoperfusion and syncope. Nonsyncopal TLOC may be due to neurologic (epilepsy, sleep attacks, and other states with fluctuating vigilance), medical (hypoglycemia, drugs), psychiatric, or post-traumatic disorders. Basic diagnostic workup of TLOC includes a thorough history and physical examination, and a 12-lead electrocardiogram (ECG). Blood testing, electroencephalogram (EEG), magnetic resonance imaging (MRI) of the brain, echocardiography, head-up tilt test, carotid sinus massage, Holter monitoring, and loop recorders should be obtained only in specific contexts. Management strategies involve pharmacologic and nonpharmacologic interventions, and cardiac pacing.

Accuracy of the withdrawal reflex for localization of the site of cervical disk herniation in dogs: 35 cases (2004-2007)

OBJECTIVE To evaluate the accuracy of neurologic examination versus magnetic resonance imaging (MRI) in localization of cervical disk herniation and evaluate the usefulness of withdrawal reflex testing in dogs. DESIGN Retrospective case series. ANIMALS 35 client-owned dogs with a single-level cervical disk herniation as determined via MRI. PROCEDURES 1 of 2 board-certified neurologists performed a complete neurologic examination in each dog. Clinical signs of a cervical lesion included evidence of neck pain and tetraparesis. The withdrawal reflex was used for neuroanatomic localization (C1-C5 or C6-T2). Agreement between results of neurologic and MRI examinations was determined. RESULTS Agreement between neurologic and MRI diagnoses was 65.8%. In 11 dogs in which the lesion was clinically localized to the C6-T2 segment on the basis of a decreased withdrawal reflex in the forelimbs, MRI revealed an isolated C1-C5 disk lesion. In 1 dog, in which the lesion was suspected to be at the C1-C5 level, MRI revealed a C6-T2 lesion. Cranial cervical lesions were significantly associated with an incorrect neurologic diagnosis regarding site of the lesion. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that the withdrawal reflex in dogs with cervical disk herniation is not reliable for determining the affected site and that a decreased withdrawal reflex does not always indicate a lesion from C6 to T2.

Minimally invasive photopolymerization in intervertebral disc tissue cavities

Photopolymerized hydrogels are commonly used for a broad range of biomedical applications. As long as the polymer volume is accessible, gels can easily be hardened using light illumination. However, in clinics, especially for minimally invasive surgery, it becomes highly challenging to control photopolymerization. The ratios between polymerization- volume and radiating-surface-area are several orders of magnitude higher than for ex-vivo settings. Also tissue scattering occurs and influences the reaction. We developed a Monte Carlo model for photopolymerization, which takes into account the solid/liquid phase changes, moving solid/liquid-boundaries and refraction on these boundaries as well as tissue scattering in arbitrarily designable tissue cavities. The model provides a tool to tailor both the light probe and the scattering/absorption properties of the photopolymer for applications such as medical implants or tissue replacements. Based on the simulations, we have previously shown that by adding scattering additives to the liquid monomer, the photopolymerized volume was considerably increased. In this study, we have used bovine intervertebral disc cavities, as a model for spinal degeneration, to study photopolymerization in-vitro. The cavity is created by enzyme digestion. Using a custom designed probe, hydrogels were injected and photopolymerized. Magnetic resonance imaging (MRI) and visual inspection tools were employed to investigate the successful photopolymerization outcomes. The results provide insights for the development of novel endoscopic light-scattering polymerization probes paving the way for a new generation of implantable hydrogels.

Use of contrast-enhanced fluid-attenuated inversion recovery sequence to detect brain lesions in dogs and cats.

BACKGROUND The diagnostic value of a contrast-enhanced T2-weighted FLAIR sequence (ceFLAIR) in brain imaging is unclear. HYPOTHESIS/OBJECTIVES That the number of brain lesions detected with ceFLAIR would be no greater than the sum of lesions detected with nFLAIR and ceT1W sequence. ANIMALS One hundred and twenty-nine animals (108 dogs and 21 cats) undergoing magnetic resonance imaging (MRI) of the head between July 2010 and October 2011 were included in the study. METHODS A transverse ceFLAIR was added to a standard brain MRI protocol. Presence and number of lesions were determined based on all available MRI sequences by 3 examiners in consensus and lesion visibility was evaluated for nFLAIR, ceFLAIR, and ceT1W sequences. RESULTS Eighty-three lesions (58 intra-axial and 25 extra-axial) were identified in 51 patients. Five lesions were detected with nFLAIR alone, 2 with ceT1W alone, and 1 with ceFLAIR alone. Significantly higher numbers of lesions were detected using ceFLAIR than nFLAIR (76 versus 67 lesions; P = 0.04), in particular for lesions also detected with ceT1W images (53 versus 40; P =.01). There was no significant difference between the number of lesions detected with combined nFLAIR and ceT1W sequences compared to those detected with ceFLAIR (82 versus 76; P =.25). CONCLUSION AND CLINICAL IMPORTANCE Use of ceFLAIR as a complementary sequence to nFLAIR and ceT1W sequences did not improve the detection of brain lesions and cannot be recommended as part of a routine brain MRI protocol in dogs and cats with suspected brain lesions.

Cerebral High-grade Oligodendroglioma with Sarcomatous Transdifferentiation ("Oligosarcoma") in a Boxer Dog.

A 9-year-old Boxer dog was referred to the Veterinary Teaching Hospital of the University of Bern for a history of chronic neck pain and gait problems, which rapidly progressed to a non-ambulatory status. Magnetic resonance imaging (MRI) examination of the head revealed a large intra-axial space-occupying lesion that was divided in two portions interconnected by a thin isthmus at the level of the cerebellar tentorium. Histopathology revealed a biphasic malignant neoplasm composed of neuroepithelial and mesenchymal elements. The former displayed characteristics of conventional anaplastic oligodendroglioma involving brisk mitotic activity and glomeruloid microvascular proliferation on a background of a fibrillary round cells with "honeycomb-like" perinuclear vacuolation. Conversely, the sarcomatous moiety exhibited haphazard fascicles of spindle cells amidst an intricate mesh of pericellular basal lamina and broad bands of collagen. Both tumor cell populations immunoreacted for Olig-2 and – to a lesser extent – GFAP. In addition, the sarcomatous areas focally expressed vimentin, muscular actin, and smooth muscle actin. "Oligosarcoma" - an exquisitely uncommon pattern of oligodendroglial malignancy in humans - has not previously been reported to affect dogs, although oligodendroglioma is a common CNS tumor in this species. Whether canine oligosarcoma shares with its human counterpart not only morphological aspects, but also molecular signatures, clinical behavior and responsiveness to therapy merits further investigation. In humans, oligodendroglial differentiation tends to confer significant clinical advantage with respect to prognosis and adjuvant treatment options. The awareness of such hallmarks and the investigation of their impact on prognosis are crucial for improved therapeutical strategies in dogs.

Size and shape of the lunate surface in different types of pincer impingement: theoretical implications for surgical therapy.

OBJECTIVE Acetabular rim trimming is indicated in pincer hips with an oversized lunate surface but could result in a critically decreased size of the lunate surface in pincer hips with acetabular malorientation. There is a lack of detailed three-dimensional anatomy of lunate surface in pincer hips. Therefore, we questioned how does (1) size and (2) shape of the lunate surface differ among hips with different types of pincer impingement? METHOD We retrospectively compared size and shape of the lunate surface between acetabular retroversion (48 hips), deep acetabulum (34 hips), protrusio acetabuli (seven hips), normal acetabuli (30 hips), and hip dysplasia (45 hips). Using magnetic resonance imaging (MRI) arthrography with radial slices we measured size in percentage of the femoral head coverage and shape using the outer (inner) center-edge angles and width of lunate surface. RESULTS Hips with retroversion had a decreased size and deep hips had normal size of the lunate surface. Both had a normal shape of the outer acetabular rim. Protrusio hips had an increased size and a prominent outer acetabular rim. In all three types of pincer hips the acetabular fossa was increased. CONCLUSION Size and shape of the lunate surface differs substantially among different types of pincer impingement. In contrast to hips with protrusio acetabuli, retroverted and deep hips do not have an increased size of the lunate surface. Acetabular rim trimming in retroverted and deep hips should be performed with caution. Based on our results, acetabular reorientation would theoretically be the treatment of choice in retroverted hips.

Echinococcus metacestode: in search of viability markers

Epidemiological studies have demonstrated that most humans infected with Echinococcus spp. exhibit resistance to disease. When infection leads to disease, the parasite is partially controlled by host immunity: in case of immunocompetence, the normal alveolar echinococcosis (AE) or cystic echinococcosis (CE) situation, the metacestode grows slowly, and first clinical signs appear years after infection; in case of impaired immunity (AIDS; other immunodeficiencies), uncontrolled proliferation of the metacestode leads to rapidly progressing disease. Assessing Echinococcus multilocularis viability in vivo following therapeutic interventions in AE patients may be of tremendous benefit when compared with the invasive procedures used to perform biopsies. Current options are F18-fluorodeoxyglucose-positron emission tomography (FDG-PET), which visualizes periparasitic inflammation due to the metabolic activity of the metacestode, and measurement of antibodies against recEm18, a viability-associated protein, that rapidly regresses upon metacestode inactivation. For Echinococcus granulosus, similar prognosis-associated follow-up parameters are still lacking but a few candidates may be listed. Other possible markers include functional and diffusion-weighted Magnetic Resonance Imaging (MRI), and measurement of products from the parasite (circulating antigens or DNA), and from the host (inflammation markers, cytokines, or chemokines). Even though some of them have been promising in pilot studies, none has been properly validated in an appropriate number of patients until now to be recommended for further use in clinical settings. There is therefore still a need to develop reliable tools for improved viability assessment to provide the sufficient information needed to reliably withdraw anti-parasite benzimidazole chemotherapy, and a basis for the development of new alternative therapeutic tools.

New ischaemic brain lesions in cervical artery dissection stratified to antiplatelets or anticoagulants.

BACKGROUND AND PURPOSE To determine the frequency of new ischaemic or hemorrhagic brain lesions on early follow-up magnetic resonance imaging (MRI) in patients with cervical artery dissection (CAD) and to investigate the relationship with antithrombotic treatment. METHODS This prospective observational study included consecutive CAD patients with ischaemic or non-ischaemic symptoms within the preceding 4 weeks. All patients had baseline brain MRI scans at the time of CAD diagnosis and follow-up MRI scans within 30 days thereafter. Ischaemic lesions were detected by diffusion-weighted imaging (DWI), intracerebral bleeds (ICBs) by paramagnetic-susceptible sequences. Outcome measures were any new DWI lesions or ICBs on follow-up MRI scans. Kaplan-Meier statistics and calculated odds ratios with 95% confidence intervals were used for lesion occurrence, baseline characteristics and type of antithrombotic treatment (antiplatelet versus anticoagulant). RESULTS Sixty-eight of 74 (92%) CAD patients were eligible for analysis. Median (interquartile range) time interval between baseline and follow-up MRI scans was 5 (3-10) days. New DWI lesions occurred in 17 (25%) patients with a cumulative 30-day incidence of 41.3% (standard error 8.6%). Occurrence of new DWI lesions was associated with stroke or transient ischaemic attack at presentation [7.86 (2.01-30.93)], occlusion of the dissected vessel [4.09 (1.24-13.55)] and presence of DWI lesions on baseline MRI [6.67 (1.70-26.13)]. The type of antithrombotic treatment had no impact either on occurrence of new DWI lesions [1.00 (0.32-3.15)] or on functional 6-month outcome [1.27 (0.41-3.94)]. No new ICBs were observed. CONCLUSION New ischaemic brain lesions occurred in a quarter of CAD patients, independently of the type of antithrombotic treatment. MRI findings could potentially serve as surrogate outcomes in pilot treatment trials.

Myositides : What is the current situation?

This article gives a review of the classification, diagnostic procedures and treatment of idiopathic inflammatory myopathies from a neurological point of view. The myositis syndromes can be subdivided into four groups, polymyositis (PM), dermatomyositis (DM), inclusion body myositis (IBM) and necrotizing myopathy (NM), which substantially differ clinically and pathophysiologically. Myositis may also occur in association with cancer or autoimmune systemic diseases (overlap syndrome). Diagnosis of inflammatory myopathies is based on clinical symptoms, determination of creatine phosphokinase and acute phase parameters in blood (e.g. C-reactive protein and erythrocyte sedimentation rate), electromyography results and findings of magnetic resonance imaging (MRI) in muscle. A muscle biopsy is mandatory to confirm the diagnosis. High quality randomized controlled trials of treatment regimens for inflammatory myopathies are sparse; however, empirical experience indicates a clear effectiveness of immunosuppressive treatment of PM, DM and NM.

Virtopsy: postmortem minimally invasive angiography using cross section techniques--implementation and preliminary results.

Postmortem investigation is increasingly supported by Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). This led to the idea to implement a noninvasive or minimally invasive autopsy technique. Therefore, a minimally invasive angiography technique becomes necessary, in order to support the vascular cross section diagnostic. Preliminary experiments investigating different contrast agents for CT and MRI and their postmortem applicability have been performed using an ex-vivo porcine coronary model. MSCT and MRI angiography was performed in the porcine model. Three human corpses were investigated using minimally invasive MSCT angiography. Via the right femoral artery a plastic tube was advanced into the aortic arch. Using a flow adjustable pump the radiopaque contrast agent meglumine-ioxithalamate was injected. Subsequent MSCT scanning provided an excellent anatomic visualization of the human arterial system including intracranial and coronary arteries. Vascular pathologies such as calcification, stenosis and injury were detected. Limitations of the introduced approach are cases of major vessel injury and cases that show an advanced stage of decay.

Postmortem non-invasive virtual autopsy: death by hanging in a car.

A body was found behind a car with a noose tied around its neck, the other end of the rope tied to a tree. Apparently the man committed suicide by driving away with the noose tied around his neck and was dragged out of the car through the open hatchback. postmortem multislice-computed tomography (MSCT) and magnetic resonance imaging (MRI) indicated that the cause of death was cerebral hypoxia due to classic strangulation by hanging, and not due to a brainstem lesion because of a hang-man fracture as would be expected in such a dynamic situation. Furthermore, the MRI displayed intramuscular haemorrhage, bleeding into the clavicular insertions of the sternocleidomastoid muscles and subcutaneous neck tissue. We conclude that MSCT and MRI are useful instruments with an increased value compared with 2D radiographs to augment the external findings of bodies when an autopsy is refused. But further postmortem research and comparing validation is needed.

Visualization and quantification of air embolism structure by processing postmortem MSCT data.

Venous air embolism (VAE) is an often occurring forensic finding in cases of injury to the head and neck. Whenever found, it has to be appraised in its relation to the cause of death. While visualization and quantification is difficult at traditional autopsy, Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) offer a new potential in the diagnosis of VAE. This paper reports the findings of VAE in four cases of massive head injury examined postmortem by Multislice Computed Tomography (MSCT) prior to autopsy. MSCT data of the thorax were processed using 3D air structure reconstruction software to visualize air embolism within the vascular system. Quantification of VAE was done by multiplying air containing areas on axial 2D images by their reconstruction intervals and then by summarizing the air volumes. Excellent 3D visualization of the air within the vascular system was obtained in all cases, and the intravascular gas volume was quantified.