MRI preclinical detection and asymptomatic course of a progressive multifocal leucoencephalopathy (PML) under natalizumab therapy.

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 ▲]

Resting state activity in patients with disorders of consciousness.

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 ▲]

Natalizumab induces a rapid improvement of disability status and ambulation after failure of previous therapy in relapsing-remitting multiple sclerosis.

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 ▲]

Neuroimaging after coma.

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 ▲]

Magnetic resonance spectroscopy and diffusion tensor imaging in coma survivors: promises and pitfalls.

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 ▲]

Functional connectivity in the default network during resting state is preserved in a vegetative but not in a brain dead patient.

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 ▲]