Assessment of White Matter Injury and Outcome in Severe Brain Trauma: A Prospective Multicenter Cohort
; ; et al
in Anesthesiology (2012), 117(6), 1300-1310
BACKGROUND:: Existing methods to predict recovery after severe traumatic brain injury lack accuracy. The aim of this study is to determine the prognostic value of quantitative diffusion tensor imaging ... [more ▼]
BACKGROUND:: Existing methods to predict recovery after severe traumatic brain injury lack accuracy. The aim of this study is to determine the prognostic value of quantitative diffusion tensor imaging (DTI). METHODS:: In a multicenter study, the authors prospectively enrolled 105 patients who remained comatose at least 7 days after traumatic brain injury. Patients underwent brain magnetic resonance imaging, including DTI in 20 preselected white matter tracts. Patients were evaluated at 1 yr with a modified Glasgow Outcome Scale. A composite DTI score was constructed for outcome prognostication on this training database and then validated on an independent database (n = 38). DTI score was compared with the International Mission for Prognosis and Analysis of Clinical Trials Score. RESULTS:: Using the DTI score for prediction of unfavorable outcome on the training database, the area under the receiver operating characteristic curve was 0.84 (95% CI: 0.75-0.91). The DTI score had a sensitivity of 64% and a specificity of 95% for the prediction of unfavorable outcome. On the validation-independent database, the area under the receiver operating characteristic curve was 0.80 (95% CI: 0.54-0.94). On the training database, reclassification methods showed significant improvement of classification accuracy (P < 0.05) compared with the International Mission for Prognosis and Analysis of Clinical Trials score. Similar results were observed on the validation database. CONCLUSIONS:: White matter assessment with quantitative DTI increases the accuracy of long-term outcome prediction compared with the available clinical/radiographic prognostic score. [less ▲]Detailed reference viewed: 6 (2 ULg)
MRI preclinical detection and asymptomatic course of a progressive multifocal leucoencephalopathy (PML) under natalizumab therapy.
Phan-Ba, Rémy ; LOMMERS, Emilie ; TSHIBANDA, Luaba et al
in Journal of Neurology, Neurosurgery & Psychiatry (2012), 83
Early detection of progressive multifocal leucoencephalopathy (PML) in the setting of natalizumab therapy currently is performed by rapid evaluation of new symptoms occurring in treated patients. The role ... [more ▼]
Early detection of progressive multifocal leucoencephalopathy (PML) in the setting of natalizumab therapy currently is performed by rapid evaluation of new symptoms occurring in treated patients. The role of MR scanning has not been investigated but holds promise since MR detection is highly sensitive for PML lesions. The authors report a case of presymptomatic PML of the posterior fossa detected by MR scans. Immediate suspension of natalizumab and plasma exchanges resulted in a rapid decline of natalizumab serum concentration. Intravenous steroids started together with plasma exchanges followed by an oral tapering course were used to minimise the immune reconstitution inflammatory syndrome. No symptoms (beyond mild headache) developed, and the repeat PCR for JC Virus (JCV) DNA detection performed 10 weeks later was negative. This case suggests that: (1) periodic brain MR scans may detect signs of presymptomatic PML in MS patients treated with natalizumab, (2) corticosteroid management of inflammatory reaction may contribute to optimal control of the immune reconstitution inflammatory syndrome routinely seen with natalizumab-associated PML and (3) early radiological detection of PML can have an excellent outcome even in a clinically critical region and despite prior immunosuppressant exposure. The potential benefit of regular MR scanning just using the T2/FLAIR modalities could be further investigated in order to detect early natalizumab-associated PML, leading to benign outcomes. [less ▲]Detailed reference viewed: 31 (6 ULg)
Multimodal neuroimaging in patients with disorders of consciousness showing "functional hemispherectomy".
Bruno, Marie-Aurélie ; ; Lehembre, Remy et al
in Progress in Brain Research (2011), 193
Beside behavioral assessment of patients with disorders of consciousness, neuroimaging modalities may offer objective paraclinical markers important for diagnosis and prognosis. They provide information ... [more ▼]
Beside behavioral assessment of patients with disorders of consciousness, neuroimaging modalities may offer objective paraclinical markers important for diagnosis and prognosis. They provide information on the structural location and extent of brain lesions (e.g., morphometric MRI and diffusion tensor imaging (DTI-MRI) assessing structural connectivity) but also their functional impact (e.g., metabolic FDG-PET, hemodynamic fMRI, and EEG measurements obtained in "resting state" conditions). We here illustrate the role of multimodal imaging in severe brain injury, presenting a patient in unresponsive wakefulness syndrome (UWS; i.e., vegetative state, VS) and in a "fluctuating" minimally conscious state (MCS). In both cases, resting state FDG-PET, fMRI, and EEG showed a functionally preserved right hemisphere, while DTI showed underlying differences in structural connectivity highlighting the complementarities of these neuroimaging methods in the study of disorders of consciousness. [less ▲]Detailed reference viewed: 28 (1 ULg)
Resting state activity in patients with disorders of consciousness.
Soddu, Andrea ; Vanhaudenhuyse, Audrey ; et al
in Functional Neurology (2011), 26(1), 37-43
Recent advances in the study of spontaneous brain activity have demonstrated activity patterns that emerge with no task performance or sensory stimulation; these discoveries hold promise for the study of ... [more ▼]
Recent advances in the study of spontaneous brain activity have demonstrated activity patterns that emerge with no task performance or sensory stimulation; these discoveries hold promise for the study of higher-order associative network functionality. Additionally, such advances are argued to be relevant in pathological states, such as disorders of consciousness (DOC), i.e., coma, vegetative and minimally conscious states. Recent studies on resting state activity in DOC, measured with functional magnetic resonance imaging (fMRI) techniques, show that functional connectivity is disrupted in the task-negative or the default mode network. However, the two main approaches employed in the analysis of resting state functional connectivity data (i.e., hypothesis-driven seed-voxel and data-driven independent component analysis) present multiple methodological difficulties, especially in non-collaborative DOC patients. Improvements in motion artifact removal and spatial normalization are needed before fMRI resting state data can be used as proper biomarkers in severe brain injury. However, we anticipate that such developments will boost clinical resting state fMRI studies, allowing for easy and fast acquisitions and ultimately improve the diagnosis and prognosis in the absence of DOC patients' active collaboration in data acquisition. [less ▲]Detailed reference viewed: 27 (4 ULg)
Natalizumab to kill two birds with one stone: A case of celiac disease and multiple sclerosis.
Phan-Ba, Rémy ; LAMBINET, Nadine ; Louis, Edouard et al
in Inflammatory Bowel Diseases (2011), 17(6), 62-63Detailed reference viewed: 36 (16 ULg)
Natalizumab induces a rapid improvement of disability status and ambulation after failure of previous therapy in relapsing-remitting multiple sclerosis.
Belachew, Shibeshih ; Phan-Ba, Rémy ; et al
in European Journal of Neurology (2010), 18(2), 240-245
Background: Natalizumab (Tysabri) is a monoclonal antibody that was recently approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). Our primary objective was to analyse the efficacy ... [more ▼]
Background: Natalizumab (Tysabri) is a monoclonal antibody that was recently approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). Our primary objective was to analyse the efficacy of natalizumab on disability status and ambulation after switching patients with RRMS from other disease-modifying treatments (DMTs). Methods: A retrospective, observational study was carried out. All patients (n = 45) initiated natalizumab after experiencing at least 1 relapse in the previous year under interferon-beta (IFNB) or glatiramer acetate (GA) treatments. The patients also had at least 1 gadolinium-enhancing (Gd+) lesion on their baseline brain MRI. Expanded Disability Status Scale (EDSS) scores, and performance on the Timed 25-Foot Walk Test and on the Timed 100-Metre Walk Test were prospectively collected every 4 weeks during 44 weeks of natalizumab treatment. Brain MRI scans were performed after 20 and 44 weeks of treatment. Results: Sixty-two per cent of patients showed no clinical and no radiological signs of disease activity, and 29% showed a rapid and confirmed EDSS improvement over 44 weeks of natalizumab therapy. Patients with improvement on the EDSS showed similar levels of baseline EDSS and active T1 lesions, but had a significantly higher number of relapses, and 92% of them had experienced relapse-mediated sustained EDSS worsening in the previous year. A clinically meaningful improvement in ambulation speed was observed in approximately 30% of patients. Conclusions: These results indicate that natalizumab silences disease activity and rapidly improves disability status and walking performance, possibly through delayed relapse recovery in patients with RRMS who had shown a high level of disease activity under other DMTs. [less ▲]Detailed reference viewed: 149 (33 ULg)
Default network connectivity reflects the level of consciousness in non-communicative brain-damaged patients.
Vanhaudenhuyse, Audrey ; Noirhomme, Quentin ; Tshibanda, Luaba et al
in Brain : A Journal of Neurology (2010), 133(Pt 1), 161-71
The 'default network' is defined as a set of areas, encompassing posterior-cingulate/precuneus, anterior cingulate/mesiofrontal cortex and temporo-parietal junctions, that show more activity at rest than ... [more ▼]
The 'default network' is defined as a set of areas, encompassing posterior-cingulate/precuneus, anterior cingulate/mesiofrontal cortex and temporo-parietal junctions, that show more activity at rest than during attention-demanding tasks. Recent studies have shown that it is possible to reliably identify this network in the absence of any task, by resting state functional magnetic resonance imaging connectivity analyses in healthy volunteers. However, the functional significance of these spontaneous brain activity fluctuations remains unclear. The aim of this study was to test if the integrity of this resting-state connectivity pattern in the default network would differ in different pathological alterations of consciousness. Fourteen non-communicative brain-damaged patients and 14 healthy controls participated in the study. Connectivity was investigated using probabilistic independent component analysis, and an automated template-matching component selection approach. Connectivity in all default network areas was found to be negatively correlated with the degree of clinical consciousness impairment, ranging from healthy controls and locked-in syndrome to minimally conscious, vegetative then coma patients. Furthermore, precuneus connectivity was found to be significantly stronger in minimally conscious patients as compared with unconscious patients. Locked-in syndrome patient's default network connectivity was not significantly different from controls. Our results show that default network connectivity is decreased in severely brain-damaged patients, in proportion to their degree of consciousness impairment. Future prospective studies in a larger patient population are needed in order to evaluate the prognostic value of the presented methodology. [less ▲]Detailed reference viewed: 75 (19 ULg)
Neuroimaging after coma.
Tshibanda, Luaba ; Vanhaudenhuyse, Audrey ; Boly, Mélanie et al
in Neuroradiology (2010), 52(1), 15-24
Following coma, some patients will recover wakefulness without signs of consciousness (only showing reflex movements, i.e., the vegetative state) or may show non-reflex movements but remain without ... [more ▼]
Following coma, some patients will recover wakefulness without signs of consciousness (only showing reflex movements, i.e., the vegetative state) or may show non-reflex movements but remain without functional communication (i.e., the minimally conscious state). Currently, there remains a high rate of misdiagnosis of the vegetative state (Schnakers et. al. BMC Neurol, 9:35, 8) and the clinical and electrophysiological markers of outcome from the vegetative and minimally conscious states remain unsatisfactory. This should incite clinicians to use multimodal assessment to detect objective signs of consciousness and validate para-clinical prognostic markers in these challenging patients. This review will focus on advanced magnetic resonance imaging (MRI) techniques such as magnetic resonance spectroscopy, diffusion tensor imaging, and functional MRI (fMRI studies in both "activation" and "resting state" conditions) that were recently introduced in the assessment of patients with chronic disorders of consciousness. [less ▲]Detailed reference viewed: 30 (4 ULg)
Natalizumab induced freedom from disease activity after failure to previous therapy in relapsing remitting multiple sclerosis.
Belachew, Shibeshih ; ; DELVAUX, Valérie et al
Conference (2009, June)
Objectives: To analyze the efficacy of natalizumab after switching relapsing-remitting multiple sclerosis (RRMS) patients from other disease modifying treaments (DMTs). Background: Natalizumab (Tysabri ... [more ▼]
Objectives: To analyze the efficacy of natalizumab after switching relapsing-remitting multiple sclerosis (RRMS) patients from other disease modifying treaments (DMTs). Background: Natalizumab (Tysabri) is a monoclonal antibody directed against VLA4 that was recently approved for the treatment of RRMS. Due to safety concerns, the use should be restricted to highly active patients and/or patients with insufficient response to other DMTs. The pivotal trials were not designed to examine the effect of natalizumab as an escalation monotherapy. Methods: Prospective, open label, observational study. All patients initiating natalizumab had experienced at least 1 relapse in the previous year under DMTs and had at least 1 Gd-enhancing lesion on their brain MRI. Previous treatment with interferon-beta (IFN-beta) or glatiramer acetate (GA) were stopped at least one week and azathioprine or mitoxantrone at least 3 months before switching. The minimum therapy duration with natalizumab was 6 months for all patients. 21 RRMS patients were included in this analysis. The mean age of the patients was 25,5 yo with mean disease duration of 6,8 years. All patients were under IFN-beta (17) or GA (4) during at least the previous year before starting natalizumab therapy. Four patients had also received azathioprine and 1 patient mitoxantrone. Results: The mean relapse rate in the previous year was 2.15 (1-4), the mean EDSS at baseline was 3.3 (1,0-6.0), the mean number of Gd+ lesions at baseline 2,58 (1-6). Under tysabri treatment the annualized relapse rate dropped to 0,20. Eleven patients improved their EDSS (0,5 to 1,5 steps down), others remained stable at 6 months. The mean number of Gd+ T1 lesions dropped to 0,23 and the mean number of new T2 lesions was 0.25 on the control MRI at 6 months. 55% of patients were free from disease activity, i.e. had no relapses, no EDSS progression, no new T2 lesion and no Gd+ T1 lesions after 6 months of Tysabri. 5 patients experienced minor adverse events (1 zona, 2 flu-like symptoms, 1 gastroenteritis, 1 allergic reaction). Conclusion: Natalizumab was well tolerated and safe as escalation therapy when previous DMTs had failed to control disease progression in this group of highly active RRMS patients. These results suggest comparable efficacy to the phase III AFFIRM trial of natalizumab when the drug is used in a context of breakthrough disease. Although data from preliminary analyses are promising, long term investigations are warranted. [less ▲]Detailed reference viewed: 17 (0 ULg)
Magnetic resonance spectroscopy and diffusion tensor imaging in coma survivors: promises and pitfalls.
TSHIBANDA, Luaba ; Vanhaudenhuyse, Audrey ; et al
in Progress in Brain Research (2009), 177
The status of comatose patient is currently established on the basis of the patient-exhibited behaviors. Clinical assessment is subjective and, in 40% of patients, fails to distinguish vegetative state ... [more ▼]
The status of comatose patient is currently established on the basis of the patient-exhibited behaviors. Clinical assessment is subjective and, in 40% of patients, fails to distinguish vegetative state (VS) from minimally conscious states (MCS). The technologic advances of magnetic resonance imaging (MRI) have dramatically improved our understanding of these altered states of consciousness. The role of neuroimaging in coma survivors has increased beyond the simple evaluation of morphological abnormalities. The development of 1H-MR spectroscopy (MRS) and diffusion tensor imaging (DTI) provide opportunity to evaluate processes that cannot be approached by current morphologic MRI sequences. They offer potentially unique insights into the histopathology of VS and MCS. The MRS is a powerful noninvasive imaging technique that enables the in vivo quantification of certain chemical compound or metabolites as N-acetylaspartate (NAA), Choline (Cho), and Creatine (Cr). These biomarkers explore neuronal integrity (NAA), cell membrane turnover (Cho), and cell energetic function (Cr). DTI is an effective and proved quantitative method for evaluating tissue integrity at microscopic level. It provides information about the microstructure and the architecture of tissues, especially the white matter. Various physical parameters can be extracted from this sequence: the fractional anisotropy (FA), a marker of white matter integrity; mean diffusivity (MD); and the apparent diffusion coefficient (ADC) which can differentiate cytotoxic and vasogenic edema. The most prominent findings with MRS and DTI performed in traumatic brain-injured (TBI) patients in subacute phase are the reduction of the NAA/Cr ratio in posterior pons and the decrease of mean infratentorial and supratentorial FA except in posterior pons that enables to predict unfavorable outcome at 1 year from TBI with up to 86% sensitivity and 97% specificity. This review will focus on the interest of comatose patients MRI multimodal assessment with MRS and DTI. It will emphasize the advantages and pitfalls of these techniques in particular in predicting the coma survivors' outcome. [less ▲]Detailed reference viewed: 8 (4 ULg)
Functional connectivity in the default network during resting state is preserved in a vegetative but not in a brain dead patient.
Boly, Mélanie ; Tshibanda, Luaba ; Vanhaudenhuyse, Audrey et al
in Human Brain Mapping (2009), 30(8), 2393-400
Recent studies on spontaneous fluctuations in the functional MRI blood oxygen level-dependent (BOLD) signal in awake healthy subjects showed the presence of coherent fluctuations among functionally ... [more ▼]
Recent studies on spontaneous fluctuations in the functional MRI blood oxygen level-dependent (BOLD) signal in awake healthy subjects showed the presence of coherent fluctuations among functionally defined neuroanatomical networks. However, the functional significance of these spontaneous BOLD fluctuations remains poorly understood. By means of 3 T functional MRI, we demonstrate absent cortico-thalamic BOLD functional connectivity (i.e. between posterior cingulate/precuneal cortex and medial thalamus), but preserved cortico-cortical connectivity within the default network in a case of vegetative state (VS) studied 2.5 years following cardio-respiratory arrest, as documented by extensive behavioral and paraclinical assessments. In the VS patient, as in age-matched controls, anticorrelations could also be observed between posterior cingulate/precuneus and a previously identified task-positive cortical network. Both correlations and anticorrelations were significantly reduced in VS as compared to controls. A similar approach in a brain dead patient did not show any such long-distance functional connectivity. We conclude that some slow coherent BOLD fluctuations previously identified in healthy awake human brain can be found in alive but unaware patients, and are thus unlikely to be uniquely due to ongoing modifications of conscious thoughts. Future studies are needed to give a full characterization of default network connectivity in the VS patients population. [less ▲]Detailed reference viewed: 78 (19 ULg)
Intrinsic brain activity in altered states of consciousness: how conscious is the default mode of brain function?
Boly, Mélanie ; Phillips, Christophe ; Tshibanda, Luaba et al
in Annals of the New York Academy of Sciences (2008), 1129
Spontaneous brain activity has recently received increasing interest in the neuroimaging community. However, the value of resting-state studies to a better understanding of brain-behavior relationships ... [more ▼]
Spontaneous brain activity has recently received increasing interest in the neuroimaging community. However, the value of resting-state studies to a better understanding of brain-behavior relationships has been challenged. That altered states of consciousness are a privileged way to study the relationships between spontaneous brain activity and behavior is proposed, and common resting-state brain activity features observed in various states of altered consciousness are reviewed. Early positron emission tomography studies showed that states of extremely low or high brain activity are often associated with unconsciousness. However, this relationship is not absolute, and the precise link between global brain metabolism and awareness remains yet difficult to assert. In contrast, voxel-based analyses identified a systematic impairment of associative frontoparieto-cingulate areas in altered states of consciousness, such as sleep, anesthesia, coma, vegetative state, epileptic loss of consciousness, and somnambulism. In parallel, recent functional magnetic resonance imaging studies have identified structured patterns of slow neuronal oscillations in the resting human brain. Similar coherent blood oxygen level-dependent (BOLD) systemwide patterns can also be found, in particular in the default-mode network, in several states of unconsciousness, such as coma, anesthesia, and slow-wave sleep. The latter results suggest that slow coherent spontaneous BOLD fluctuations cannot be exclusively a reflection of conscious mental activity, but may reflect default brain connectivity shaping brain areas of most likely interactions in a way that transcends levels of consciousness, and whose functional significance remains largely in the dark. [less ▲]Detailed reference viewed: 66 (6 ULg)