Antiepileptic drug use and epileptic seizures in nursing home residents in the Province of Pavia, Italy: A reappraisal 12 years after a first survey.

PURPOSE: To assess the prevalence of epileptic seizures, and antiepileptic drug (AED) use among nursing home elderly residents; to evaluate demographics, seizure characteristics, and seizure-related comorbidities associated with institutionalization; and to compare findings with a previous survey conducted 12 years earlier. METHODS: Data on demographics, age at institutionalization, diagnoses, functional and cognitive status (Barthel Index and Mini Mental State Examination) and drug treatment were obtained by review of medical records of all individuals aged ≥ 60 years at 21 nursing homes. Data from individuals with a diagnosis of epileptic seizures and AED users were compared with non-seizure, non-AED individuals. RESULTS: Among the 2163 individuals surveyed (79% females, age at observation 84.9 ± 7.8 years, mean ± SD), 278 (12.8%, vs 4.3% in the previous survey) received chronic AED treatment, including 174 who did not have a diagnosis of seizures. Of the 116 residents with a diagnosis of seizures (5.4%, vs 2.9% in the previous study), 104 were on AED treatment and were younger and had lower cognitive abilities, and a higher number of comorbidities and co-medications compared with non-AED-users. The most commonly prescribed AEDs in seizure individuals were phenobarbital (43.3%, vs 70% in the previous survey) and levetiracetam (27.9%, not available at the time of previous survey). At multivariate analysis, a diagnosis of seizures was found to be associated with younger age at the time of the survey, a history of neurological (cerebrovascular events, meningiomas) and non-neurological conditions (psoriasis and chronic bronchitis), and a lower MMSE score. CONCLUSIONS: The prevalence of seizures and AED use was higher than in our previous survey and more aligned with data from other countries. Seizures, AED use and co-morbidities were associated with earlier institutionalization. There were indicators of treatment being suboptimal in many cases.

Interictal spiking in adult newly-diagnosed focal epilepsy of unknown cause: The effect of age.

OBJECTIVE: To assess the yield of interictal EEG spiking in standard and whole-night sleep EEGs in elderly subjects with recent-onset focal seizures compared to younger patients. METHODS: Detection of interictal epileptiform abnormalities (IEAs) and rating of mean spike index (number of interictal discharges/minute) values for different sleep stages (NREM stages 1-2 and 3-4 and REM sleep) in standard EEG (S-EEG) and 24-h ambulatory EEG (A-EEG) at first referral in three groups of thirty consecutive outpatients [aged 20-39 (young), 40-59 (adults) and ⩾60years (elderly)], retrospectively selected according to a subsequent diagnosis of focal epilepsy of unknown cause, no sleep disorders or drugs or comorbidities affecting sleep and EEG. RESULTS: Elderly subjects showed a lower rate of IEAs on S-EEG (p<0.01) but a higher propensity for spiking during deep NREM sleep, 11/30 showing IEAs exclusively during stages 3-4. Mean spike index showed a significant increase in IEAs between sleep stages 1-2 and 3-4 in the elderly subjects (p<0.001). CONCLUSIONS: A significant association emerged between IEAs during deep sleep and age (p<0.001). SIGNIFICANCE: EEG recordings covering deep NREM sleep should be recommended when IEAs detection is needed to support a diagnosis of epilepsy in elderly subjects.

Modulation of intracellular proline levels affects flowering time and inflorescence architecture in Arabidopsis.

We reported previously that the plant oncogene rolD anticipates and stimulates flowering in Nicotiana tabacum, and encodes ornithine cyclodeaminase, an enzyme catalysing the conversion of ornithine to proline. To investigate on the possible role of proline in flowering, we altered the expression of AtP5CS1, encoding the rate-limiting enzyme of proline biosynthesis in plants. Accordingly we characterized a mutant line containing a T-DNA insertion into AtP5CS1 and introduced in Arabidopsis thaliana AtP5CS1 under the control of the CaMV35S promoter. As expected homozygous p5cs1 mutants behaved as late flowering. In addition p5cs1 mutants exhibited a shorter size and contained lower levels of proline, compared to wild type. 35S-P5CS1 plants, manifested, early in development, overexpression of P5CS1 and accumulation of proline, leading to early flowering, both under long- and short-day conditions. Later in development, down-regulation of P5CS1 occurred in 35S-P5CS1 leaves, leading to proline reduction, and, in turn, impaired bolting and stunted growth. Salt-stress restored expression of P5CS1 and proline accumulation in P5CS1-transformed plants, as well as rescuing growth. Our data suggest that proline plays a key role in flower transition, bolting and coflorescence formation.

The PDZ-GEF dizzy regulates cell shape of migrating macrophages via Rap1 and integrins in the Drosophila embryo.

In Drosophila embryos, macrophages originate from the cephalic mesoderm and perform a complex migration throughout the entire embryo. The molecular mechanisms regulating this cell migration remain largely unknown. We identified the Drosophila PDZ G-nucleotide exchange factor (PDZ-GEF) Dizzy as a component essential for normal macrophage migration. In mutants lacking Dizzy, macrophages have smaller cellular protrusions, and their migration is slowed down significantly. This phenotype appears to be cell-autonomous, as it is also observed in embryos with a dsRNA-induced reduction of dizzy function in macrophages. In a complementary fashion, macrophages overexpressing Dizzy are vastly extended and form very long protrusions. These cell shape changes depend on the function of the small GTPase Rap1: in rap1 mutants, Dizzy is unable to induce the large protrusions. Furthermore, forced expression of a dominant-active form of Rap1, but not of the wild-type form, induces similar cell shape changes as Dizzy does overexpression. These findings suggest that Dizzy acts through Rap1. We propose that integrin-dependent adhesion is a Rap1-mediated target of Dizzy activity: in integrin mutants, neither Dizzy nor Rap1 can induce cell shape changes in macrophages. These data provide the first link between a PDZ-GEF, the corresponding small GTPase and integrin-dependent cell adhesion during cell migration in embryonic development.