Brain : a journal of neurology
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Randomized Controlled Trial
Results of a phase II placebo-controlled randomized trial of minocycline in acute spinal cord injury.
Preclinical studies have attributed neuroprotective properties to the antibiotic minocycline. Animal studies and early clinical trials support its use in several neurological diseases. In animal spinal cord injury models, minocycline improved neurological and histological outcomes, reduced neuronal and oligodendroglial apoptosis, decreased microglial activation and reduced inflammation. ⋯ The minocycline regimen established in this study proved feasible, safe and was associated with a tendency towards improvement across several outcome measures. Although this study does not establish the efficacy of minocycline in spinal cord injury the findings are encouraging and warrant further investigation in a multi-centre phase III trial. ClinicalTrials.gov number NCT00559494.
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Randomized Controlled Trial
Delayed treatment with chondroitinase ABC promotes sensorimotor recovery and plasticity after stroke in aged rats.
Stroke is the dominant cause of sensorimotor disability that primarily affects the elderly. We now show that neuroplasticity and functional recovery after stroke is constrained by inhibitory chondroitin sulphates. In two blinded, randomized preclinical trials, degradation of chondroitin sulphate using chondroitinase ABC reactivated neuroplasticity and promoted sensorimotor recovery after stroke in elderly rats. ⋯ Anterograde and retrograde tracing showed that chondroitinase ABC also induced sprouting of the contralesional corticospinal tract in the aged treated hemicord. Chondroitinase ABC did not neuroprotect the peri-infarct region. We show for the first time delayed chondroitinase ABC treatment promotes neuroanatomical and functional recovery after focal ischaemic stroke in an elderly nervous system.
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Mild traumatic brain injury is the most prevalent neurological insult and frequently results in neurobehavioural sequelae. However, little is known about the pathophysiology underlying the injury and how these injuries change as a function of time. Although diffusion tensor imaging holds promise for in vivo characterization of white matter pathology, both the direction and magnitude of anisotropic water diffusion abnormalities in axonal tracts are actively debated. ⋯ A spatially heterogeneous pattern of increased anisotropic diffusion exists in various other white matter tracts, and these white matter anomalies appear to diminish with recovery. This macroscopic pattern of diffusion abnormalities may be associated with cytotoxic oedema following mechanical forces, resulting in changes in ionic homeostasis, and alterations in the ratio of intracellular and extracellular water. Animal models more specific to the types of mild traumatic brain injury typically incurred by humans are needed to confirm the histological correlates of these macroscopic markers of white matter pathology.
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Axonal injury is believed to be a major determinant of adverse outcomes following traumatic brain injury. However, it has been difficult to assess acutely the severity of axonal injury in human traumatic brain injury patients. We hypothesized that microdialysis-based measurements of the brain extracellular fluid levels of tau and neurofilament light chain, two low molecular weight axonal proteins, could be helpful in this regard. ⋯ Taken together, our data add support for the hypothesis that axonal injury may be related to long-term impairments following traumatic brain injury. Microdialysis-based measurement of tau levels in the brain extracellular space may be a useful way to assess the severity of axonal injury acutely in the intensive care unit. Further studies with larger numbers of patients will be required to assess the reproducibility of these findings and to determine whether this approach provides added value when combined with clinical and radiological information.
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Patients surviving severe brain injury may regain consciousness without recovering their ability to understand, move and communicate. Recently, electrophysiological and neuroimaging approaches, employing simple sensory stimulations or verbal commands, have proven useful in detecting higher order processing and, in some cases, in establishing some degree of communication in brain-injured subjects with severe impairment of motor function. To complement these approaches, it would be useful to develop methods to detect recovery of consciousness in ways that do not depend on the integrity of sensory pathways or on the subject's ability to comprehend or carry out instructions. ⋯ In contrast, in minimally conscious patients, who showed fluctuating signs of non-reflexive behaviour, transcranial magnetic stimulation invariably triggered complex activations that sequentially involved distant cortical areas ipsi- and contralateral to the site of stimulation, similar to activations we recorded in locked-in, conscious patients. Longitudinal measurements performed in patients who gradually recovered consciousness revealed that this clear-cut change in effective connectivity could occur at an early stage, before reliable communication was established with the subject and before the spontaneous electroencephalogram showed significant modifications. Measurements of effective connectivity by means of transcranial magnetic stimulation combined with electroencephalography can be performed at the bedside while by-passing subcortical afferent and efferent pathways, and without requiring active participation of subjects or language comprehension; hence, they offer an effective way to detect and track recovery of consciousness in brain-injured patients who are unable to exchange information with the external environment.