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This study identifies by microautoradiography activated microglia/macrophages as the main cell type expressing the peripheral benzodiazepine binding site (PBBS) at sites of active CNS pathology. Quantitative measurements of PBBS expression in vivo obtained by PET and [(11)C](R)-PK11195 are shown to correspond to animal experimental and human post-mortem data on the distribution pattern of activated microglia in inflammatory brain disease. Film autoradiography with [(3)H](R)-PK11195, a specific ligand for the PBBS, showed minimal binding in normal control CNS, whereas maximal binding to mononuclear cells was found in multiple sclerosis plaques. However, there was also significantly increased [(3)H](R)-PK11195 binding on activated microglia outside the histopathologically defined borders of multiple sclerosis plaques and in areas, such as the cerebral central grey matter, that are not normally reported as sites of pathology in multiple sclerosis. A similar pattern of [(3)H](R)-PK11195 binding in areas containing activated microglia was seen in the CNS of animals with experimental allergic encephalomyelitis (EAE). In areas without identifiable focal pathology, immunocytochemical staining combined with high-resolution emulsion autoradiography demonstrated that the cellular source of [(3)H](R)-PK11195 binding is activated microglia, which frequently retains a ramified morphology. Furthermore, in vitro radioligand binding studies confirmed that microglial activation leads to a rise in the number of PBBS and not a change in binding affinity. Quantitative [(11)C](R)-PK11195 PET in multiple sclerosis patients demonstrated increased PBBS expression in areas of focal pathology identified by T(1)- and T(2)-weighted MRI and, importantly, also in normal-appearing anatomical structures, including cerebral central grey matter. The additional binding frequently delineated neuronal projection areas, such as the lateral geniculate bodies in patients with a history of optic neuritis. In summary, [(11)C](R)-PK11195 PET provides a cellular marker of disease activity in vivo in the human brain.

Summary: Purpose: Lamotrigine is an effective add-on therapy against a range of epileptic seizure types. Comparative studies with carbainaLepine (CBZ) as monotherapy in newly diagnosed epilepsy suggest similar efficacy. In this study, lamotrigine (LTG) and phenytoin (PHT) are compared.Methods: In a double-blind parallel-groups study. I X 1 patients with newly diagnosed untreated partial seizures or secondarily or primary generalised tonic-clonic seizures were randoniised to two treatment groups. One group (n = 86) received LTG titrated over 6 weeks from a starting dose of 100 mg/day. The other (ti = 95) received PHT titrated from 200 ing/tlay. Treatment continued for 5 4 8 weeks. K i~s i d t x ;The percentages of patients remaining on each treatment and seiLure frec during the last 24 and 40 weeks of the study, and times to first seizure after the first 6 weeks of treatment (dose-titration period). did not differ significantly between the treatment groups. These were measures of efficacy. Time to discontinuation, a composite index of effi safety, likewise did not distinguish between treatments. Adverse events led to discontinuation of 13 (IS%) patients from LTG and 18 ( 1 9%) from PHT. The adverse-event profile for LTG w.as dominated by skin rash (discontinuation of 10 (11.6%) patients compared with five (5.3%) from PHT] rather than central nervous system side effect sthenia, somnolence, and ataxia were each significantly inore frequent in the PHT group. The high rate of rash with LTG was probably due to the high starting dose and may be avoidable. A quality-of-life instrument. the SEALS inventory, favoured LTG. Patients taking PHT showed the biochemical changes expected of an eiizyrneinducing drug, whereas those taking LTG did not.Cotwlusiot~.~: LTG and PHT monotherapy were similarly effective against these seizure types in patients with newly diagnosed epilepsy. LTG was better tolerated, inore frequently causing rash. but with a lower incidence of central nervous system side effects.

No abstract

The interrelation of neurology and the gastrointestinal system includes defects of gut innervation, primary disorders of the nervous system (or muscle) which lead to gastrointestinal symptoms-for example, dysphagia-and, finally, certain gut disorders which include neurological features in their clinical range. The first of this trio will be discussed only briefly in this review, the second and third in more detail.