Nature reviews. Neurology
-
Nature reviews. Neurology · Jan 2014
ReviewDelayed neurological deterioration after subarachnoid haemorrhage.
Subarachnoid haemorrhage (SAH) causes early brain injury (EBI) that is mediated by effects of transient cerebral ischaemia during bleeding plus effects of the subarachnoid blood. Secondary effects of SAH include increased intracranial pressure, destruction of brain tissue by intracerebral haemorrhage, brain shift, and herniation, all of which contribute to pathology. Many patients survive these phenomena, but deteriorate days later from delayed cerebral ischaemia (DCI), which causes poor outcome or death in up to 30% of patients with SAH. ⋯ Prompt recognition of DCI and immediate treatment by means of induced hypertension and balloon or pharmacological angioplasty are considered important by many physicians, although the evidence to support such approaches is limited. This Review summarizes the pathophysiology of DCI after SAH and discusses established treatments for this condition. Novel strategies--including drugs such as statins, sodium nitrite, albumin, dantrolene, cilostazol, and intracranial delivery of nimodipine or magnesium--are also discussed.
-
Cortical spreading depression (CSD), a slowly propagated wave of depolarization followed by suppression of brain activity, is a remarkably complex event that involves dramatic changes in neural and vascular function. Since its original description in the 1940s, CSD has been hypothesized to be the underlying mechanism of the migraine aura. ⋯ Considerable uncertainty about the role of CSD in migraine remains, however, and key questions about how this event is initiated, how it spreads, and how it might cause migraine symptoms remain unanswered. This Review summarizes current concepts of CSD and its potential roles in migraine, and addresses ongoing studies aimed at a clearer understanding of this fundamental brain phenomenon.
-
Nature reviews. Neurology · Oct 2013
ReviewImaging in sepsis-associated encephalopathy--insights and opportunities.
Sepsis-associated encephalopathy (SAE) refers to a clinical spectrum of acute neurological dysfunction that arises in the context of sepsis. Although the pathophysiology of SAE is incompletely understood, it is thought to involve endothelial activation, blood-brain barrier leakage, inflammatory cell migration, and neuronal loss with neurotransmitter imbalance. SAE is associated with a high risk of mortality. ⋯ Next-generation imaging techniques such as magnetic resonance spectroscopy, diffusion tensor imaging and PET, as well as experimental imaging modalities, provide options for early identification of patients with SAE, and could aid in identification of pathophysiological processes that represent possible therapeutic targets. In this Review, we explore the recent literature on imaging in SAE, relating the findings of these studies to pathological data and experimental studies to obtain insights into the pathophysiology of sepsis-associated neurological dysfunction. Furthermore, we suggest how novel imaging technologies can be used for early-stage proof-of-concept and proof-of-mechanism translational studies, which may help to improve diagnosis in SAE.
-
Nature reviews. Neurology · Oct 2013
ReviewReappraising neuropathic pain in humans--how symptoms help disclose mechanisms.
Neuropathic pain--that is, pain arising directly from a lesion or disease that affects the somatosensory system--is a common clinical problem, and typically causes patients intense distress. Patients with neuropathic pain have sensory abnormalities on clinical examination and experience pain of diverse types, some spontaneous and others provoked. Spontaneous pain typically manifests as ongoing burning pain or paroxysmal electric shock-like sensations. ⋯ Paroxysmal sensations can be caused by several mechanisms; for example, electric shock-like sensations probably arise from high-frequency bursts generated in demyelinated non-nociceptive Aβ fibres. Most human and animal findings suggest that brush-evoked allodynia originates from Aβ fibres projecting onto previously sensitized nociceptive neurons in the dorsal horn, with additional contributions from plastic changes in the brainstem and thalamus. Here, we propose that the emerging mechanism-based approach to the study of neuropathic pain might aid the tailoring of therapy to the individual patient, and could be useful for drug development.
-
Nature reviews. Neurology · Sep 2013
Review Historical Article25 years of neuroimaging in amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease for which a precise cause has not yet been identified. Standard CT or MRI evaluation does not demonstrate gross structural nervous system changes in ALS, so conventional neuroimaging techniques have provided little insight into the pathophysiology of this disease. ⋯ Given their potential for investigation of both brain structure and function, advanced neuroimaging methods offer important opportunities to improve diagnosis, guide prognosis, and direct future treatment strategies in ALS. In this article, we review the contributions made by various advanced neuroimaging techniques to our understanding of the impact of ALS on different brain regions, and the potential role of such measures in biomarker development.