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Introduction: Natalizumab is a monoclonal antibody that inhibits leukocyte migration across the blood-brain barrier and has been approved for the treatment of relapsing-remitting multiple sclerosis., Objective: To provide a review and update of the pharmacological and therapeutic characteristics of natalizumab, with special emphasis on the most recently published data on the efficacy, effectiveness and safety of this drug., Development: Several randomized clinical trials in patients with relapsing forms of multiple sclerosis have demonstrated that natalizumab substantially reduces clinical and radiological disease activity. Post hoc analysis of phase III clinical trials and the results of post-approval observational studies indicate that natalizumab significantly increases the proportion of patients with complete clinical and radiological response and is effective in patients with highly active forms of multiple sclerosis and suboptimal response to other treatments. Like other monoclonal antibodies, natalizumab can cause hypersensitivity reactions, which are severe in 1% of patients. Other adverse effects are generally mild or infrequent. Nevertheless, several cases of progressive multifocal leukoencephalopathy have been detected in patients treated with natalizumab monotherapy. The risk of this severe complication seems to increase with the number of doses administered., Conclusion: Natalizumab has a favorable risk-benefit ratio in the treatment of relapsing -remitting multiple sclerosis. However, because of the potential risk of progressive multifocal leukoencephalopathy, patients must be carefully selected and specific protocols must be followed during the drug's administration., (Copyright © 2010 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.)

Objective: To review the basic concepts and mechanisms of cerebral edema and to analyze current management of this complex clinical problem., Development: Cerebral edema is a stereotyped reaction of the brain to any aggression and is a very common complication in patients with alterations of the blood-brain barrier. The cerebral edema should be recognized and treated early and aggressively to avoid disastrous results such as cerebral herniation. The most important types of edema are the vasogenic and cytotoxic. The first implies primary alterations of the blood-brain barrier, whilst in the second they are of cellular homeostasis. We have reviewed how various pro-inflammatory substances interact to stimulate the mechanisms causing edema, and also the importance of cerebrovascular autoregulation for maintenance of a normal intracranial volume. The measures necessary for good cerebral reanimation are the following: evaluation of the airway, controlled hyperventilation, maintenance of the cerebral perfusion pressure > 70 mmHg, suitable position of the head, administration of hypertonic solutions, dexamethasone, and possibly barbiturates. We have shown that a body temperature > 37.5 degrees C and blood glucose > 150 mg/dl are related to worsening of the cerebral edema. Finally, we have reviewed other experimental treatments which seem promising, such as hemicraniectomy, hypertonic saline solutions, hypothermia and other neuroprotector agents., Conclusions: All patients with acute cerebral edema should be evaluated early and treated with therapy which will solve the underlying pathological problem. Good medical management of these patients is of vital importance to assure a satisfactory clinical outcome. Recently new, effective therapy has been evaluated which may substantially change current concepts of the treatment of patients with acute cerebral edema.

A high resolution cytochemical study was performed in cats to investigate the cerebral blood vessel permeability to low molecular weight non-liposoluble substances. Sodium ferrocyanide was injected to four adult cats through an intraventricular canula and a copper solution was perfused intravascularly. Electroencephalographic recording throughout the experiments showed no detectable alterations induced by the administered solutions. Brain fragments fixed by intravascular perfusion were processed for electron microscopy. Pineal gland from the same animals and masseter muscle fragments in which ferrocyanide had been directly injected in those animals were studied as controls. A copper ferrocyanide suspension was directly injected into the lateral ventricle to two cats and 15 min later the brains were fixed by perfusion and processed for electron microscopy. An electrondense precipitate was seen in the interstitial and perivascular space, but not into the vessel lumen in these animals. No reaction product was observed in the brain parenchyma of cats injected intraventricularly with sodium ferrocyanide, whereas electron-dense deposits were clearly depicted in the pineal gland and masseter muscle in the same animals. The results further support the thesis that the junctions between the endothelial cells in brain capillaries represent a physical barrier to non-liposoluble substances.