Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
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Traumatic, spinal cord injury (SCI) is a potentially catastrophic event causing major impact at both a personal and societal level. To date, virtually all therapies that have shown promise at the preclinical stage of study have failed to translate into clinically effective treatments. ⋯ Results of the multicenter, Surgical Trial in Acute Spinal Cord Injury Study (STASCIS), expected later this year, should further clarify this important management issue. The overall goal of this review is to provide an update regarding the current status of surgical therapy for traumatic SCI by reviewing relevant pathophysiology, laboratory, and clinical evidence, as well as to introduce radiologic and clinical tools that aid in the surgical decision-making process.
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Spinal cord injury (SCI) is a devastating condition that affects approximately 11,000 patients each year in the United States. Although a significant amount of research has been conducted to clarify the pathophysiology of SCI, there are limited therapeutic interventions that are currently available in the clinic. Moderate hypothermia has been used in a variety of experimental and clinical situations to target several neurological disorders, including traumatic brain and SCI. ⋯ In addition, several clinical studies have demonstrated encouraging evidence for the use of TH in patients with a severe cervical spinal cord injury. Moderate hypothermia (33°C) introduced systemically by intravascular cooling strategies appears to be safe and provides some improvement of long-term recovery of function. TH remains an experimental clinical approach and randomized multicenter trials are needed to critically evaluate this potentially exciting therapeutic intervention targeting this patient population.
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Clinical management of chronic pain after nerve injury (neuropathic pain) and tumor invasion (cancer pain) is a real challenge due to our limited understanding of the cellular mechanisms that initiate and maintain chronic pain. It has been increasingly recognized that glial cells, such as microglia and astrocytes in the CNS play an important role in the development and maintenance of chronic pain. Notably, astrocytes make very close contacts with synapses and astrocyte reaction after nerve injury, arthritis, and tumor growth is more persistent than microglial reaction, and displays a better correlation with chronic pain behaviors. ⋯ The MCP-1 increases pain sensitivity via direct activation of NMDA receptors in dorsal horn neurons. Pharmacological inhibition of the IL-1β, c-Jun N-terminal kinase, MCP-1, or matrix metalloprotease-2 signaling via spinal administration has been shown to attenuate inflammatory, neuropathic, or cancer pain. Therefore, interventions in specific signaling pathways in astrocytes may offer new approaches for the management of chronic pain.
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Occipital nerve stimulation (ONS) was originally described in the treatment of occipital neuralgia. However, the spectrum of possible indications has expanded in recent years to include primary headache disorders, such as migraine and cluster headaches. Retrospective and some prospective studies have yielded encouraging results, and evidence from controlled clinical trials is emerging, offering hope for refractory headache patients. ⋯ This requires multidisciplinary assessment of patients. The development of ONS as a new treatment for refractory headache offers an exciting prospect to treat our most disabled headache patients. Data from ongoing controlled trials will undoubtedly shed new light on some of the unresolved questions.
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Transcranial magnetic stimulation (TMS) is a diagnostic and therapeutic modality that is being developed as both an acute and preventive treatment for migraine. TMS delivers a fluctuating magnetic field from the scalp surface to induce current in the subjacent cortex. Magnetic pulses are delivered one at a time in single-pulse TMS (sTMS) or as a train of pulses in repetitive TMS (rTMS). ⋯ Based on the theory that rTMS alters brain excitability and neurotransmitter activity, rTMS has been studied as a preventive migraine treatment. A small body of evidence suggests that rTMS may have a role, but further studies are needed. In this review, we summarize the data on TMS as a treatment of migraine, and we suggest directions for future research.