Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
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Direct neuroaxis drug delivery has expanded the physician's armamentarium to provide treatment options to those who have failed more conservative interventions. Starting from Bier's 'cocainization of the spinal cord' in 1898, direct nervous system pharmacy delivery has long been recognized as an effective means to treat pain. Intrathecal pump systems are now commonplace in the management of numerous pain states, as well as of neuromuscular sequelae of central nervous system injury. ⋯ As well, surgical techniques and catheter systems have undergone refinements providing improved long-term safety and efficacy. We present a review of the historical evolution to current intrathecal therapies, as well as a dialog regarding patient selection, drug options, and side effects. Also, included is a discussion of surgical techniques, current delivery options and complications concerning pump placement.
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Peripheral nerve stimulation (PNS) has been used for treatment of neuropathic pain for more than 40 years. Recent resurgence of interest to this elegant surgical modality came from the introduction of less invasive implantation techniques and the wider acceptance of neuromodulation as a treatment of medically refractory cases. ⋯ PNS works well in both established indications, such as post-traumatic and postsurgical neuropathy, occipital neuralgia, and complex regional pain syndromes, and in relatively new indications for neuromodulation, such as migraines and daily headaches, cluster headaches, and fibromyalgia. Future research and growing clinical experience will help in identifying the best candidates for PNS, choosing the best procedure and best hardware for each individual patient, and defining adequate expectations for patients and pain specialists.
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Many patients who suffer from medically refractory epilepsy are not candidates for resective brain surgery. Success of deep brain stimulation (DBS) in relieving a significant number of symptoms of various movement disorders paved the way for investigations into this modality for epilepsy. ⋯ Thus, it is difficult as yet to make any definitive judgments about the efficacy of DBS for seizure control. Future study is necessary to identify a patient population for whom this technique would be indicated, the most efficacious target, and optimal stimulation parameters.
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In the diseased brain, upon activation microglia express binding sites for synthetic ligands designed to recognize the 18-kDa translocator protein TP-18, which is part of the so-called peripheral benzodiazepine receptor complex. PK11195 [1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide], the prototype synthetic ligand, has been widely used for the functional characterization of TP-18. Its cellular source in activated microglia has been established using high-resolution, single-cell autoradiography with the R-enantiomer [3H](R)-PK11195. ⋯ Thus, a profile of active disease emerges that matches some of the typical distribution patterns known from structural neuroimaging techniques, but additionally shows involvement of brain regions linked through neural pathways. In the context of cell-based in vivo neuropathology, the image data are thus best interpreted in the context of the emerging cellular understanding of brain disease or damage, rather than the definitions of clinical diagnosis. One important observation, borne out by experiment, is the long latency with which activated microglia or increased PK11195 retention appear to gradually emerge and remain in distal areas secondarily affected by disease, supporting speculations that the presence of activated microglia is an important corollary of brain plasticity.
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Medical care of patients with dementia often occurs within a physician-patient relationship whose features differ from relationships with patients without dementia. Many basic assumptions of the physician-patient relationship may not completely hold true, and certain aspects of the patient role may be shared by others besides the patient. For example, the entire premise of consent to the patient role may be inapplicable to patients who lack insight into their illness. ⋯ This can lead to viewing patients as collections of symptoms rather than as humans suffering with illnesses and burdens. The fact that certain medical interventions, such as treatment of neuropsychiatric disturbances that do not trouble the patient, may appear to be initiated for the primary purpose of alleviating caregiver emotional stress also affects the physician-patient relationship. The present review examines how this relationship may be altered and presents a framework within which these alterations can be considered.