Brain : a journal of neurology
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Chronic pain is a frequent component of many neurological disorders, affecting 20-40% of patients for many primary neurological diseases. These diseases result from a wide range of pathophysiologies including traumatic injury to the central nervous system, neurodegeneration and neuroinflammation, and exploring the aetiology of pain in these disorders is an opportunity to achieve new insight into pain processing. Whether pain originates in the central or peripheral nervous system, it frequently becomes centralized through maladaptive responses within the central nervous system that can profoundly alter brain systems and thereby behaviour (e.g. depression). ⋯ It is critical that neurologists become more involved in chronic pain treatment and research (already significant in the fields of migraine and peripheral neuropathies). To achieve this goal, greater efforts are needed to enhance training for neurologists in pain treatment and promote greater interest in the field. This review describes examples of pain in different neurological diseases including primary neurological pain conditions, discusses the therapeutic potential of brain-targeted therapies and highlights the need for objective measures of pain.
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Review
The role of dopaminergic imaging in patients with symptoms of dopaminergic system neurodegeneration.
Diagnosis of neurological and psychiatric conditions associated with disturbances of dopaminergic functioning can be challenging, especially in the early stages, and may be assisted with biomarkers such as dopamine system imaging. Distinguishing between Alzheimer's disease and dementia with Lewy bodies is a major diagnostic challenge. Clinical diagnosis of Parkinson's disease is straightforward with classic presentation, but accurate distinction among Parkinsonian variants may be difficult; non-Parkinson's disease conditions are commonly misdiagnosed as Parkinson's disease, and ~20% of patients with Parkinson's disease are not clinically diagnosed despite coming to medical attention. ⋯ In a series of patients with post-mortem brain examination, imaging using [(123)I]ioflupane has demonstrated higher sensitivity (88%) and specificity (100%) for differentiating dementia with Lewy bodies from non-Lewy body dementia than clinical diagnosis (75% and 42%, respectively). Dopaminergic system imaging may be particularly valuable in patients with clinically inconclusive parkinsonism or a clinical diagnosis of possible dementia with Lewy bodies; it is not helpful in differentiating between Parkinson's disease and atypical parkinsonism, although postsynaptic dopaminergic imaging may be of utility. Other potential uses of dopamine transporter imaging include identification of patients with premotor Parkinson's disease, monitoring disease progression in testing novel therapeutics, and as an inclusion criterion for entry into clinical trials.
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Super-refractory status epilepticus is defined as status epilepticus that continues or recurs 24 h or more after the onset of anaesthetic therapy, including those cases where status epilepticus recurs on the reduction or withdrawal of anaesthesia. It is an uncommon but important clinical problem with high mortality and morbidity rates. This article reviews the treatment approaches. ⋯ The importance of treating the identifying cause is stressed. A protocol and flowchart for managing super-refractory status epilepticus is suggested. In view of the small number of published reports, there is an urgent need for the establishment of a database of outcomes of individual therapies.
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Demyelinating disorders of the central nervous system are among the most crippling neurological diseases affecting patients at various stages of life. In the most prominent demyelinating disease, multiple sclerosis, the regeneration of myelin sheaths often fails due to a default of the resident stem/precursor cells (oligodendrocyte precursor cells) to differentiate into mature myelin forming cells. Significant advances have been made in our understanding of the molecular and cellular processes involved in remyelination. ⋯ The pattern by which remyelination inducers and inhibitors are expressed in multiple sclerosis lesions may determine a window of opportunity during which oligodendrocyte precursor cells can successfully differentiate. As the first molecules aiming at promoting remyelination are about to enter clinical trials, this review critically evaluates recent advances in our understanding of the biology of oligodendrocyte precursor cells and of the stage-dependent molecular pathology of multiple sclerosis lesions relevant to the regeneration of myelin sheaths. We propose a model that may help to provide cues for how remyelination can be therapeutically enhanced in clinical disease.
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The motor system comprises a network of cortical and subcortical areas interacting via excitatory and inhibitory circuits, thereby governing motor behaviour. The balance within the motor network may be critically disturbed after stroke when the lesion either directly affects any of these areas or damages-related white matter tracts. A growing body of evidence suggests that abnormal interactions among cortical regions remote from the ischaemic lesion might also contribute to the motor impairment after stroke. ⋯ Based on such data, we suggest that pathological intra- and inter-hemispheric interactions among key motor regions constitute an important pathophysiological aspect of motor impairment after subcortical stroke. We also demonstrate that therapeutic interventions, such as repetitive transcranial magnetic stimulation, which aims to interfere with abnormal cortical activity, may correct pathological connectivity not only at the stimulation site but also among distant brain regions. In summary, analyses of connectivity further our understanding of the pathophysiology underlying motor symptoms after stroke, and may thus help to design hypothesis-driven treatment strategies to promote recovery of motor function in patients.