Orna Aizenstein

Bilateral hippocampal lesion and a selective impairment of the ability for mental time travel

Mental time travel allows individuals to mentally project themselves backwards and forwards in subjective time. This case report describes a young woman suddenly rendered amnesic as a result of bilateral hippocampal damage following an epileptic seizure and brain anoxia. Her neuropsychological profile was characterized by a high-average general level of cognitive functioning, selective deficit in episodic memory of past events and a significant difficulty to envisage her personal future. This case provides clinical support for the concept of mental time travel with its retrospective and prospective components and for the hippocampus being its critical neural substrate.

Retropharyngeal and parapharyngeal abscess in children--epidemiology, clinical features and treatment.

OBJECTIVE To describe the clinical presentation, diagnosis, management and complications of children with retropharyngeal abscesses (RPAs) and parapharyngeal abscesses (PPAs). METHODS A retrospective chart review was conducted at two tertiary care, pediatric hospitals in Israel. The medical records of all children <18 years who had been admitted with a diagnosis of RPA or PPA during an 11-year period (January 1997 to February 2008) were reviewed. Data on demographics, presenting symptoms, physical examination findings, imaging studies and interpretation, laboratory results, hospital course, medical treatment and surgical interventions were retrieved. RESULTS A total of 39 children were diagnosed as having RPA (n=26, 67%) or PPA (n=13, 33%). There was a predominance of boys (61.5%). The mean age of all the children at diagnosis was 4 years. The annual incidence increased over the 11-year period. The most common symptoms at presentation included fever (n=27, 70%) and neck pain (n=24, 62%). The physical examination revealed cervical lymphadenopathy in 30 children (77%), limitation of neck movements in 25 (64%), torticollis in 21 (54%), drooling in three (8%), and stridor in two (5%). Computerized tomographic (CT) scanning with contrast was performed in 37 patients (95%), of whom 17 underwent surgical drainage. Thirteen children were positively diagnosed as having an abscess by the finding of pus at surgery, of whom 12 had been found to have an abscess on their CT scan. All the patients received intravenous antibiotics. There was no significant difference in the duration of hospital stay between those who underwent surgery and those who were treated with antibiotics alone. There were no treatment failures and no complications in either of the two groups. CONCLUSION Children with RPA most commonly present with restricted neck movements, fever and cervical lymphadenopathy, and rarely with respiratory distress or stridor. Many patients with RPA and PPA can be treated successfully without surgery. CT scans are helpful in diagnosing and assessing the extent of the infection, but they are not always accurate.

Differentiation between vasogenic-edema versus tumor-infiltrative area in patients with glioblastoma during bevacizumab therapy: A longitudinal MRI study

BACKGROUND Treatment with bevacizumab is associated with substantial radiologic response in patients with glioblastoma (GB). However, following this initial response, changes in T2-weighted MRI signal may develop, suggesting an infiltrative pattern of tumor progression. The aim of this study was to differentiate between vasogenic-edema versus tumor-infiltrative area in GB patients. METHODS AND MATERIALS Fourteen patients with GB were longitudinally scanned, before and during intravenous bevacizumab therapy (5/10mg/kg every 2-weeks). A total of 40 MR scans including conventional, diffusion, dynamic susceptibility contrast, dynamic contrast enhancement imaging, and MR-spectroscopy (MRS) were analyzed. Classification of non-enhancing fluid-attenuation-inversion-recovery (FLAIR) area was performed based on mean diffusivity, cerebral blood volume and flow maps, and further characterized using multiple MRI parameters. RESULTS The non-enhancing FLAIR lesion area was classified into: vasogenic-edema, characterized by reduced perfusion and increased FLAIR values; or tumor-infiltrative area, characterized by increased perfusion. Tumor-infiltrative area demonstrated a higher malignant pattern on MRS compared to areas of vasogenic-edema. Substantial reductions of the enhanced T1-weighted (58 ± 10%) and hyperintense FLAIR (53 ± 9%) lesion volumes were detected mainly during the first weeks of therapy, with a shift to an infiltrative pattern of tumor progression thereafter, as detected by an increase in tumor-infiltrative area in the majority of patients, which correlated with progression-free survival (week 8: r=-0.86, p=0.003, week 16: r=-0.99, p=0.001). CONCLUSION Characterization of non-enhancing hyperintense FLAIR lesion area in GB patients can provide an MR-based biomarker, indicating a shift to an infiltrative progression pattern, and may improve therapy response assessment in patients following bevacizumab therapy.

Predictors for poststroke outcomes: the Tel Aviv Brain Acute Stroke Cohort (TABASCO) study protocol.

Background Recent studies have demonstrated that even survivors of mild stroke experience residual damage, which persists and in fact increases in subsequent years. About 45% of stroke victims remain with different levels of disability. Identifying factors associated with poststroke cognitive and neurological decline could potentially yield more effective therapeutic opportunities. Aims and hypothesis We hypothesize that data based on biochemical, neuroimaging, genetic and psychological measures can, in aggregate, serve as better predictors for subsequent disability, cognitive and neurological deterioration, and suggest possible interventions. Design The Tel-Aviv Brain Acute Stroke Cohort (TABASCO) study is an ongoing, prospective cohort study that will recruit approximately 1125 consecutive first-ever mild–moderate stroke patients. It is designed to evaluate the association between predefined demographic, psychological, inflammatory, biochemical, neuroimaging and genetic markers, measured during the acute phase, and long-term outcome: subsequent cognitive deterioration, vascular events (including recurrent strokes), falls, affect changes, functional everyday difficulties and mortality. Discussion This study is an attempt to comprehensively investigate the long-term outcome of mild–moderate strokes. Its prospective design will provide quantitative data on stroke recurrence, the incidence of other vascular events and the evaluation of cognitive, affective and functional decline. Identifying the factors associated with poststroke cognitive and functional decline could potentially yield more effective therapeutic approaches.

FLAIR lesion segmentation: Application in patients with brain tumors and acute ischemic stroke

BACKGROUND Lesion size in fluid attenuation inversion recovery (FLAIR) images is an important clinical parameter for patient assessment and follow-up. Although manual delineation of lesion areas considered as ground truth, it is time-consuming, highly user-dependent and difficult to perform in areas of indistinct borders. In this study, an automatic methodology for FLAIR lesion segmentation is proposed, and its application in patients with brain tumors undergoing therapy; and in patients following stroke is demonstrated. MATERIALS AND METHODS FLAIR lesion segmentation was performed in 57 magnetic resonance imaging (MRI) data sets obtained from 44 patients: 28 patients with primary brain tumors; 5 patients with recurrent-progressive glioblastoma (rGB) who were scanned longitudinally during anti-angiogenic therapy (18 MRI scans); and 11 patients following ischemic stroke. RESULTS FLAIR lesion segmentation was obtained in all patients. When compared to manual delineation, a high visual similarity was observed, with an absolute relative volume difference of 16.80% and 20.96% and a volumetric overlap error of 24.87% and 27.50% obtained for two raters: accepted values for automatic methods. Quantitative measurements of the segmented lesion volumes were in line with qualitative radiological assessment in four patients who received anti-anogiogenic drugs. In stroke patients the proposed methodology enabled identification of the ischemic lesion and differentiation from other FLAIR hyperintense areas, such as pre-existing disease. CONCLUSION This study proposed a replicable methodology for FLAIR lesion detection and quantification and for discrimination between lesion of interest and pre-existing disease. Results from this study show the wide clinical applications of this methodology in research and clinical practice.

Hemodynamic response imaging: a potential tool for the assessment of angiogenesis in brain tumors.

Blood oxygenation level dependence (BOLD) imaging under either hypercapnia or hyperoxia has been used to study neuronal activation and for assessment of various brain pathologies. We evaluated the benefit of a combined protocol of BOLD imaging during both hyperoxic and hypercapnic challenges (termed hemodynamic response imaging (HRI)). Nineteen healthy controls and seven patients with primary brain tumors were included: six with glioblastoma (two newly diagnosed and four with recurrent tumors) and one with atypical-meningioma. Maps of percent signal intensity changes (ΔS) during hyperoxia (carbogen; 95%O2+5%CO2) and hypercapnia (95%air+5%CO2) challenges and vascular reactivity mismatch maps (VRM; voxels that responded to carbogen with reduced/absent response to CO2) were calculated. VRM values were measured in white matter (WM) and gray matter (GM) areas of healthy subjects and used as threshold values in patients. Significantly higher response to carbogen was detected in healthy subjects, compared to hypercapnia, with a GM/WM ratio of 3.8 during both challenges. In patients with newly diagnosed/treatment-naive tumors (n = 3), increased response to carbogen was detected with substantially increased VRM response (compared to threshold values) within and around the tumors. In patients with recurrent tumors, reduced/absent response during both challenges was demonstrated. An additional finding in 2 of 4 patients with recurrent glioblastoma was a negative response during carbogen, distant from tumor location, which may indicate steal effect. In conclusion, the HRI method enables the assessment of blood vessel functionality and reactivity. Reference values from healthy subjects are presented and preliminary results demonstrate the potential of this method to complement perfusion imaging for the detection and follow up of angiogenesis in patients with brain tumors.

A potential tool for the diagnosis of ALS based on diffusion tensor imaging

Abstract Our objective was to quantify and better understand white matter (WM) impairment in patients with amyotrophic lateral sclerosis (ALS) and to propose a model based on diffusion tensor imaging (DTI) for diagnosing patients with suspected ALS with upper motor neuron (UMN) signs. Twenty-six ALS patients (24 with prominent UMN signs and two with an isolated lower-motor neuron (LMN) syndrome) and 22 healthy volunteers were examined using DTI. Data analysis included voxel-based WM tract-based spatial statistics (TBSS), volume-of-interest analysis of the TBSS results and stream-line tractography analysis. Converging evidence revealed WM impairment along the corticospinal tracts and in the mid-body of the corpus callosum. This was demonstrated by reduced fractional anisotropy values caused by increased radial diffusivity, without significant changes in axial diffusivity. There were no significant correlations between diffusivity indices and patients’ disability or disease duration. A discriminant analysis model based on the tractography results was designed to distinguish between patients with UMN signs and controls, yielding 87.5% sensitivity and 85% specificity. In conclusion, DTI can detect WM impairment in patients with ALS in several brain regions, and might be a sensitive tool for the diagnosis of ALS in the early stages of the disease with UMN involvement.

Automatic multi-modal MR tissue classification for the assessment of response to bevacizumab in patients with glioblastoma

BACKGROUND Current methods for evaluation of treatment response in glioblastoma are inaccurate, limited and time-consuming. This study aimed to develop a multi-modal MRI automatic classification method to improve accuracy and efficiency of treatment response assessment in patients with recurrent glioblastoma (GB). MATERIALS AND METHODS A modification of the k-Nearest-Neighbors (kNN) classification method was developed and applied to 59 longitudinal MR data sets of 13 patients with recurrent GB undergoing bevacizumab (anti-angiogenic) therapy. Changes in the enhancing tumor volume were assessed using the proposed method and compared with Macdonalds criteria and with manual volumetric measurements. The edema-like area was further subclassified into peri- and non-peri-tumoral edema, using both the kNN method and an unsupervised method, to monitor longitudinal changes. RESULTS Automatic classification using the modified kNN method was applicable in all scans, even when the tumors were infiltrative with unclear borders. The enhancing tumor volume obtained using the automatic method was highly correlated with manual measurements (N=33, r=0.96, p<0.0001), while standard radiographic assessment based on Macdonalds criteria matched manual delineation and automatic results in only 68% of cases. A graded pattern of tumor infiltration within the edema-like area was revealed by both automatic methods, showing high agreement. All classification results were confirmed by a senior neuro-radiologist and validated using MR spectroscopy. CONCLUSION This study emphasizes the important role of automatic tools based on a multi-modal view of the tissue in monitoring therapy response in patients with high grade gliomas specifically under anti-angiogenic therapy.

Only White Matter Hyperintensities Predicts Post-Stroke Cognitive Performances Among Cerebral Small Vessel Disease Markers: Results from the TABASCO Study

BACKGROUND White matter hyperintensities (WMH) were shown to predict cognitive decline following stroke or transient ischemic attack (TIA). However, WMH are only one among other radiological markers of cerebral small vessel disease (SVD). OBJECTIVE The aim of this study was to determine whether adding other SVD markers to WMH improves prediction of post-stroke cognitive performances. METHODS Consecutive first-ever stroke or TIA patients (n = 266) from the Tel Aviv Acute Brain Stroke Cohort (TABASCO) study were enrolled. MRI scans were performed within seven days of stroke onset. We evaluated the relationship between cognitive performances one year following stroke, and previously suggested total SVD burden score including WMH, lacunes, cerebral microbleeds (CMB), and perivascular spaces (PVS). RESULTS Significant negative associations were found between WMH and cognition (p < 0.05). Adding other SVD markers (lacunes, CMB, PVS) to WMH did not improve predication of post-stroke cognitive performances. Negative correlations between SVD burden score and cognitive scores were observed for global cognitive, memory, and visual spatial scores (all p < 0.05). However, following an adjustment for confounders, no associations remained significant. CONCLUSION WMH score was associated with poor post-stroke cognitive performance. Adding other SVD markers or SVD burden score, however, did not improve prediction.

Clinical considerations and key issues in the management of patients with Erdheim-Chester Disease: A seven case series

BackgroundErdheim-Chester Disease (ECD), a non Langerhans’ cell histiocytosis of orphan nature and propensity for multi-systemic presentations, comprises an intricate medical challenge in terms of diagnosis, treatment and complication management.ObjectivesThe objectives are to report the clinical, radiological and pathological characteristics, as well as cardinal therapeutic approaches to ECD patients and to provide clinical analyses of the medical chronicles of these complex patients.MethodsPatients with biopsy proven ECD were audited by a multi-disciplinary team of specialists who formed a coherent timeline of all the substantial clinical events in the evolution of their patients’ illness.ResultsSeven patients (five men, two women) were recruited to the study. The median age at presentation was 53 years (range: 39 to 62 years). The median follow-up time was 36 months (range: 1 to 72 months). Notable ECD involvement sites included the skeleton (seven), pituitary gland (seven), retroperitoneum (five), central nervous system (four), skin (four), lungs and pleura (four), orbits (three), heart and great vessels (three) and retinae (one). Prominent signs and symptoms were fever (seven), polyuria and polydipsia (six), ataxia and dysarthria (four), bone pain (four), exophthalmos (three), renovascular hypertension (one) and dyspnea (one). The V600E BRAF mutation was verified in three of six patients tested. Interferon-α treatment was beneficial in three of six patients treated. Vemurafenib yielded dramatic neurological improvement in a BRAF mutated patient. Infliximab facilitated pericardial effusion volume reduction. Cladribine improved cerebral blood flow originally compromised by perivenous lesions.ConclusionsECD is a complex, multi-systemic, clonal entity coalescing both neoplastic and inflammatory elements and strongly dependent on impaired RAS/RAF/MEK/ERK signaling.