Progress in brain research
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Levodopa therapy represents a major breakthrough in the treatment of Parkinson's disease (PD). As time and disease severity progresses, however, the shortcomings and adverse effects of this neurotransmitter replacement strategy become apparent and patients develop disabilities despite best medical therapy. The heightened awareness of these difficulties has given birth to a re-examination of functional neurosurgery for advanced PD. ⋯ Other problems are less or non-responsive. Further, despite the widespread use of this technology, the mechanism through which DBS alleviates symptoms is not fully understood. This review will discuss the patient population most likely to benefit from surgery, what aspects of the disease are most responsive, the current limitations of DBS, and new therapeutic targets that are being examined to address these limitations.
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Over the last years, a plethora of genetic findings have completely changed our views on the aetiology of Parkinson's disease (PD). Linkage studies and positional cloning strategies have identified mutations in a growing number of genes which cause monogenic autosomal-dominant or autosomal-recessive forms of the disorder. ⋯ Thus, an increasingly complex network of genes contributing in different ways to disease risk and progression is emerging. These findings provide the 'genetic entry points' to identify molecular targets and readouts necessary to design rational disease-modifying treatments.
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A dramatic paradigm shift is taking place in our understanding of the pathophysiology of multiple sclerosis (MS). An important contribution to such a shift has been made possible by the advances in magnetic resonance imaging (MRI) technology, which allows structural damage to be quantified in the brains of patients with MS and to be followed over the course of the disease. Modern quantitative MR techniques have reshaped the picture of MS, leading to the definition of the so- called "axonal hypothesis" (i.e., changes in axonal metabolism, morphology, or density are important determinants of functional impairment in MS). ⋯ The inflammatory and neurodegenerative components of the disease process are present from the earliest observable phases of the disease, but appear to be, at least partially, dissociated. In addition, recovery and repair play an important role in the genesis of the clinical manifestations of the disease, involving both structural changes and plastic reorganization of the cortex. This new picture of MS has important implications in the context of treatment options, since it suggests that agents that protect against neurodegeneration or promote tissue repair may have an important role to play alongside agents acting on the inflammatory component of the disease.
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The natural history of recovery from brain injury typically consists of a period of impaired consciousness, a subsequent period of confusion and amnesia, followed by a period of post-confusional recovery of function. Patients with more severe injuries may have more prolonged episodes of unconsciousness or minimal consciousness and may not fully evolve through this continuum of recovery. There is limited information on the course of recovery and long-term outcome of patients with prolonged unconsciousness, particularly those with extended periods in the minimally conscious state. Further, patients with impaired consciousness are frequently denied access to hospital-based rehabilitation services because of uncertain prognosis and a perceived lack of benefit from rehabilitative interventions. ⋯ Patients in VS whose transition to MCS occurred within 8 weeks of onset are likely to continue recovering to higher levels of functioning, a substantial proportion to household independence, and productive pursuits. Patients with TBI are more likely to progress than patients with nonTBI, though significant improvement in the nonTBI group is still possible. Active, higher intensity, rehabilitation should be strongly considered for patients with severely impaired consciousness after brain injury, especially for patients with TBI who have signs of progression to the MCS.
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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 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.