Retention of new AEDs in institutionalized intellectually disabled patients with epilepsy.

PURPOSE: To assess the long-term usefulness of 'new anti-epileptic drugs (AEDs)' (lamotrigine, topiramate, levetiracetam, gabapentin and pregabalin) in institutionalized intellectually disabled patients. Information from RCTs is lacking in this population with severe intellectual and behavioural disabilities. METHODS: Retrospective study. Data from the medical files and the pharmacy databases of 118 institutionalized intellectually disabled patients who had ever used at least one of the new AEDs were analyzed. The main evaluation parameters were the duration of use (using Kaplan-Meier survival estimates) and the reason for discontinuation (lack of efficacy, occurrence of adverse events, or both) of the new AEDs. Drug continuation was based on the evaluation of treatment results by experienced epileptologists, and not on fixed criteria. RESULTS: New AEDs were generally tried only after a substantial number of other regimens (with classic AEDs) had failed. The most frequently used new AEDs were lamotrigine (68%) and levetiracetam (58%), followed by topiramate (28%) and gabapentin (8%). The 3-year retention rates were 70% (lamotrigine), 52% (levetiracetam), 51% (topiramate) and 33% (gabapentin). Discontinuation due to "lack of efficacy" occurred in 61% (topiramate), 60% (lamotrigine) and 42% (levetiracetam) of the cases. Discontinuation due to adverse events occurred in 42% (levetiracetam), 33% (topiramate) and 28% (lamotrigine). CONCLUSIONS: Treatment of epilepsy with new AEDs was quite often successful in this very therapy-resistant population.

Prevalence of Parkinson's disease in the elderly: the Rotterdam Study.

We assessed the prevalence of Parkinson's disease (PD) in a general elderly population in the Netherlands. The study formed part of the Rotterdam Study, a population-based door-to-door study, and included 6,969 persons 55 years of age or older living in a suburb of Rotterdam, the Netherlands. All participants were examined, and those who either had at least one possible cardinal sign of parkinsonism at the neurologic screening, reported that they had PD, or were taking antiparkinsonian drugs were invited for further evaluation. The prevalence of PD in this population was 1.4% (1.2% for men, 1.5% for women). Prevalence increased with age, and prevalence figures were 0.3% for those aged 55 to 64 years, 1.0% for those 65 to 74, 3.1% for those 75 to 84, and 4.3% for those 85 to 94. The corresponding age-specific figures for men were 0.4%, 1.2%, 2.7%, and 3.0%, and for women, 0.2%, 0.8%, 3.4%, and 4.8%. Among 95- to 99-year-old women the prevalence was 5.0%. Twelve percent of the subjects with PD were detected through the screening and had not been diagnosed previously.

Cytochrome oxidase activity in the rat caudate nucleus: light and electron microscopic observations.

Cytochrome oxidase (CO) activity was examined in the neostriatum of normal adult rats at the light and electron microscopic level. At the light microscopic level a heterogeneous distribution of CO activity was observed and was characterized by patches of high activity ranging in size from 200 to 800 microns surrounded or adjacent to regions of lower activity. The most dorsomedial and ventromedial regions of the caudate nucleus appeared to be consistently high in activity in all animals. At the ultrastructural level CO reaction product was localized to the membranes and intracristal spaces of mitochondria. The most reactive mitochondria (those containing the denest precipitates of reaction product) were found within the dendrites of spiny neurons in all caudate regions. In areas of high CO activity the mitochondria within bundles of myelinated fibers and in many axon terminals were also highly reactive whereas those in neuronal somata, primary dendrites, and glial cells and processes exhibited relatively little activity. Quantitative study showed that mitochondria within dendrites accounted for most of the CO activity in caudate neuropil. The mitochondria within dendrites and axon terminals were more reactive in regions of high CO activity than in regions of low CO activity. No differences in the density of synapses or in the proportions of axospinous and axodendritic synapses were observed between CO-rich and CO-poor areas. Heterogeneity in the distribution of CO activity in the caudate nucleus may be related to the "patchy" pattern of localization previously observed for some neostriatal afferents, enzymes, transmitters, peptides, and receptor ligands.(ABSTRACT TRUNCATED AT 250 WORDS)

Anatomical observations on the afferent projections to the retractor bulbi motoneuronal cell group and other pathways possibly related to the blink reflex in the cat.

In the cat retractor bulbi (RB) muscle reflexively retracts the eye ball into the orbit. This reflex action is called the nictitating membrane response which, together with the reflex contraction of the orbicularis oculi muscle, constitutes the blink reflex. The retractor bulbi (RB) motoneuronal nucleus is a small cell group located in the lateral tegmentum of the caudal pons, just dorsal to the superior olivary complex. The nucleus is identical to the accessory abducens nucleus and sends its fibers through the abducens nerve. Autoradiographical tracing results indicate that the RB nucleus receives some fibers from the principal and rostral spinal trigeminal nuclei and from the dorsal red nucleus and dorsally adjoining tegmentum. The same areas project to the intermediate facial subnucleus, containing motoneurons innervating the orbicularis oculi muscle. It is suggested that the trigeminal projections take part in the anatomical framework for the R1 component of the blink reflex. Two other brainstem areas i.e.: a portion of the caudal pontine ventrolateral tegmental field and the medullary medial tegmentum at the level of the hypoglossal nucleus were also found to project to the RB motoneuronal cell group and to the intermediate facial subnucleus. These projections were much stronger than those derived from the trigeminal nuclei and red nucleus. Moreover, the medullary premotor area projects not only to the blink motoneuronal cell groups but also to the pontine premotor area. It is suggested that both areas are involved in the R2 blink reflex component. The medullary blink premotor area receives afferents especially from oculomotor control structures in the reticular formation of the brainstem while the pontine blink premotor area receives afferents from the olivary pretectal nucleus and/or the nucleus of the optic tract and from the dorsal red nucleus and its dorsally adjoining area. Because the oculomotor control structures in the reticular formation (by way of the superior colliculus) and the red nucleus receive afferents from trigeminal nuclei, they may play an important role in tactually induced reflex blinking, while the pretectum could take part in the neuronal framework of the visually induced blink reflex.

A Golgi study of the human neostriatum: neurons and afferent fibers.

The neostriatum of 20 adult humans was examined in Golgi-Kopsch and rapid Golgi preparations. At least five types of neurons and four types of afferent fibers are described. Neurons of medium size with spine-rich dendrites (spiny type I) are the most frequent type. These cells exhibit a greater morphological diversity than those previously studied in the monkey. Also, quantitative data show that, compared to the monkey, spiny type I neurons in man have a greater somal size and dendritic field radius. Although the types of spines are similar, the mean density and radial distribution of spines along dendrites differ in the two species. Morphologic features of the axon, which is usually long with extensive collateral branches, suggest that more than one process from the axon may be efferent. Medium to large neurons with sparsely spined dendrites (spiny type II) differ from type I neurons in having a poorer branching and greater radial spread of their dendrites and a lower density of spines. They also differ from spiny type I neurons in their distribution and relative proportion of various spine types. The axon of the spiny type II neuron is long and has collaterals which are poorly arborized in comparison to those of spiny type I cells. Aspiny neurons are of medium (aspiny type I) and large (aspiny type II) size. They have varicose, curved dendrites and a short axon which arborizes mostly within the dendritic field. A group of smaller neurons with more variable dendritic morphology is also seen. Observations suggest that in the human brain the proportion of medium-sized aspiny neurons and small neurons may be greater than in other species.

Evidence for degenerative and regenerative changes in neostriatal spiny neurons in Huntington's disease.

Golgi impregnations of neostriatum from deceased Huntington's disease patients and controls were examined. In all cases of Huntington's disease the morphology of dendrites of medium-sized spiny neurons was markedly altered by the appearance of recurved endings and appendages, a decrease or increase in the density of spines, and abnormalities in the size and shape of spines. Pathological changes were rarely observed in medium-sized and large aspiny neostriatal neurons. The findings provide evidence for simultaneous degeneration and growth of spiny neurons in Huntington's disease and support the view that a specific population of neostriatal neurons is selectively involved in its pathogenesis.

The frequency and distribution of medium-sized neurons with indented nuclei in the primate and rodent neostriatum.

Nuclear morphology is known to distinguish two classes of medium-sized neurons in the neostriatum, spiny projection neurons which have an unindented nucleus and aspiny interneurons which exhibit enfoldings of their nuclear envelope. The frequency and distribution of medium-sized neostriatal neurons with indented nuclei were examined in the light microscope in semi-thick sections. Results showed that the proportion of neostriatal neurons with nuclear indentations was greater in the monkey (23%) than in the mouse and rat (4-5%). Also, nuclear enfoldings were found in more neurons of the monkey caudate than putamen, whereas in the rodent regional differences were not observed. Findings suggest that aspiny interneurons play a greater role in the integrative and functional organization of the neostriatum in the primate than in the rodent brain.

Localization of immunoreactive enkephalins in GABA synthesizing neurons of the rat neostriatum.

The localization of immunoreactive glutamic acid decarboxylase (GAD) and enkephalin-like immunoreactivity was examined in serial, 4-micron frozen sections of the caudate nucleus from rats pretreated with colchicine. Colocalization was found in numerous caudate neurons of medium size. Cell counts of corresponding labeled neurons in paired adjacent sections showed that GAD and enkephalin-like immunoreactivity coexist in about one half of the caudate cell populations containing each of these substances.