Nature reviews. Neurology
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Epilepsy is the third most common chronic brain disorder, and is characterized by an enduring predisposition to generate seizures. Despite progress in pharmacological and surgical treatments of epilepsy, relatively little is known about the processes leading to the generation of individual seizures, and about the mechanisms whereby a healthy brain is rendered epileptic. These gaps in our knowledge hamper the development of better preventive treatments and cures for the approximately 30% of epilepsy cases that prove resistant to current therapies. ⋯ We first describe aspects of brain inflammation and immunity, before exploring the evidence from clinical and experimental studies for a relationship between inflammation and epilepsy. Subsequently, we discuss how seizures cause inflammation, and whether such inflammation, in turn, influences the occurrence and severity of seizures, and seizure-related neuronal death. Further insight into the complex role of inflammation in the generation and exacerbation of epilepsy should yield new molecular targets for the design of antiepileptic drugs, which might not only inhibit the symptoms of this disorder, but also prevent or abrogate disease pathogenesis.
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Dolichoectasia is an arterial disease that causes dilatation and/or tortuosity of the affected vessel. The prevalence of dolichoectasia increases with age, and this disease is also associated with other traditional cardiovascular risk factors. Multiple pathophysiological processes might lead to the development of dolichoectatic vessels, and activation of metalloproteinases and irregular turbulent blood flow seem to cause irreversible disruption of the internal elastic lamina. ⋯ No specific treatment for dolichoectasia exists, and the surgical and medical therapies that have been used to treat this condition have not been systematically evaluated. More evidence is needed to better understand the underlying dilatatory artheriopathy that causes this disease, and to determine whether patients with dolichoectasia might benefit from early diagnosis. In this article, we provide a comprehensive review of current knowledge regarding dolichoectasia, and highlight gaps in our knowledge to aid future research.
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Chemotherapy-induced peripheral neurotoxicity (CIPN) is a common, potentially severe and dose-limiting adverse effect of cancer treatment; however, the effects of CIPN on the daily life of individuals are not completely understood. CIPN can be induced by several types of drugs that are widely used in the treatment of solid and hematological malignancies. ⋯ Moreover, symptomatic therapy is often largely ineffective in reducing CIPN symptoms. In this Review, the mechanistic and clinical aspects of this unpredictable condition are considered, along with the controversial aspects of CIPN, including the onset mechanisms associated with the different drug types, assessment of the patient's condition, and the current status of neuroprotection and treatment options.
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Intracerebral hemorrhage (ICH) is a major public-health problem worldwide. No proven treatments are available for this condition, which is associated with high rates of morbidity and mortality. Only 20% of individuals who survive ICH are independent at 6 months. ⋯ Many questions remain unanswered regarding the clinical management of ICH, although in the past 10 years completed medical and surgical clinical trials-examining hemostatic therapy, blood pressure control and/or hematoma evacuation-have refined our understanding of the goals of such management. Ongoing clinical trials, which have built on the lessons of past studies, hold promise for the development of effective, scientifically proven treatments for ICH. In this Review, we discuss clinical trials for ICH that have been completed in the past 10 years, the contributions of these studies to the clinical management of ICH, and the ongoing trials that might further improve clinical care.