Late-onset myoclonic epilepsy in Down’s syndrome (LOMEDS)

AbstractThe aim of this paper is to report a patient with late-onset myoclonic epilepsy in Down’s syndrome (LOMEDS) as a differential diagnosis of adult-onset progressive myoclonic epilepsies. A 55-year-old male with Down’s syndrome (DS) is described who developed progressively frequent myoclonus and generalized myoclonic–tonic seizures (GMTSs) at the age of 52. EEG recordings demonstrated background slowing and generalized polyspike-wave discharges occasionally associated with myoclonic jerks, leading to the classification of primary generalized epileptic myoclonus. Descriptions of late-onset epilepsy in DS patients are rare. However, a review of the pertinent literature revealed at least two other cases of elderly DS patients developing progressive myoclonic epilepsy after the onset of dementia. We suggest that late-onset myoclonic epilepsy in Down’s syndrome as characterized here should be considered in the differential diagnosis of adult-onset myoclonic epilepsies. LOMEDS apparently shares features with myoclonic epilepsy in Alzheimer’s disease (AD) and Unverricht–Lundborg disease (ULD) caused by a mutation on chromosome 21. Since life expectation of DS patients has markedly increased, LOMEDS may be more frequent than currently acknowledged

Catechol-O-methyltransferase inhibition with tolcapone reduces the "wearing off" phenomenon and levodopa requirements in fluctuating parkinsonian patients.

BACKGROUND: More than 50% of patients with Parkinson's disease develop motor response fluctuations (the "wearing off" phenomenon) after more than five years of levodopa therapy. Inhibition of catechol-O-methyltransferase by tolcapone has been shown to increase levodopa bioavailability and plasma elimination half life, thereby prolonging the efficacy of levodopa. OBJECTIVES: The primary objective was to evaluate the efficacy of tolcapone in reducing "wearing off" in levodopa treated, fluctuating parkinsonian patients. Secondary objectives included assessment of reduction in levodopa requirements, improvement in patients' clinical status, duration of improvements, and tolerability of tolcapone. METHODS: In this multicentre, randomised, double blind, placebo controlled trial, 58 patients received placebo, 60 received 100 mg tolcapone three times daily (tid), and 59 received 200 mg tolcapone tid, in addition to levodopa/benserazide. RESULTS: After three months with 200 mg tolcapone tid, "off" time decreased by 26.2% of the baseline value, "on" time increased by 20.6% (P<O.01 v placebo), and the mean total daily levodopa dose decreased by 122 mg from the baseline dose of 676 mg (P<0.01). These responses were maintained up to nine months. With 100 mg tolcapone tid, "off" time decreased by 31.5% (P<0.05), "on" time increased by 21.3% (P<0.01), and the mean total daily levodopa dose decreased by 109 mg from the baseline dose of 668 mg (P<0.05). With 200 mg tolcapone tid, unified Parkinson's disease rating scale motor and total scores were significantly reduced, and quality of life (sickness impact profile) scores were significantly improved. Both dosages were well tolerated. Dyskinesia was the most often reported levodopa induced adverse event. Diarrhea was the most often reported non-dopaminergic adverse event and the most frequent reason for withdrawal from the study: four patients in the 100 mg tolcapone tid group and six in the 200 mg tid group withdrew because of diarrhea. CONCLUSION: Tolcapone prolongs "on" time in fluctuating parkinsonian patients while allowing a reduction in daily levodopa dosage, thereby improving the efficacy of long term levodopa therapy

The comorbidity profiles and medication issues of patients with multiple system atrophy: a systematic cross-sectional analysis

Background Multiple system atrophy (MSA) is a complex and fatal neurodegenerative movement disorder. Understanding the comorbidities and drug therapy is crucial for MSA patients’ safety and management. Objectives To investigate the pattern of comorbidities and aspects of drug therapy in MSA patients. Methods Cross-sectional data of MSA patients according to Gilman et al. (2008) diagnostic criteria and control patients without neurodegenerative diseases (non-ND) were collected from German, multicenter cohorts. The prevalence of comorbidities according to WHO ICD-10 classification and drugs administered according to WHO ATC system were analyzed. Potential drug-drug interactions were identified using AiDKlinik®. Results The analysis included 254 MSA and 363 age- and sex-matched non-ND control patients. MSA patients exhibited a significantly higher burden of comorbidities, in particular diseases of the genitourinary system. Also, more medications were prescribed MSA patients, resulting in a higher prevalence of polypharmacy. Importantly, the risk of potential drug-drug interactions, including severe interactions and contraindicated combinations, was elevated in MSA patients. When comparing MSA-P and MSA-C subtypes, MSA-P patients suffered more frequently from diseases of the genitourinary system and diseases of the musculoskeletal system and connective tissue. Conclusions MSA patients face a substantial burden of comorbidities, notably in the genitourinary system. This, coupled with increased polypharmacy and potential drug interactions, highlights the complexity of managing MSA patients. Clinicians should carefully consider these factors when devising treatment strategies for MSA patients

Open data from the third observing run of LIGO, Virgo, KAGRA, and GEO

The global network of gravitational-wave observatories now includes five detectors, namely LIGO Hanford, LIGO Livingston, Virgo, KAGRA, and GEO 600. These detectors collected data during their third observing run, O3, composed of three phases: O3a starting in 2019 April and lasting six months, O3b starting in 2019 November and lasting five months, and O3GK starting in 2020 April and lasting two weeks. In this paper we describe these data and various other science products that can be freely accessed through the Gravitational Wave Open Science Center at https://gwosc.org. The main data set, consisting of the gravitational-wave strain time series that contains the astrophysical signals, is released together with supporting data useful for their analysis and documentation, tutorials, as well as analysis software packages

Effekt von Zink auf die Olfaktion und Motorik von Patienten mit Morbus Parkinson

Parkinson-Patienten weisen erniedrigte Zink-Spiegel im Liquor auf und zeigen Symptome eines funktionellen Zinkmangels. Zinkmangel macht sich für gewöhnlich in einer gestörten Geruchsempfindung bemerkbar. Da ein sehr großer Anteil der Parkinson-Patienten an einer Riechstörung leidet, wurde die Hypothese aufgestellt, dass diese Hyposmie bei Morbus Parkinson durch Zinksubstitution reversibel ist. Deshalb wurde in einer Studie mit kleiner Fallzahl (16 Patienten) der Effekt von Zink auf das Riechvermögen sowie auf die Motorik bei Patienten mit Morbus Parkinson untersucht („proof-of-principle“). Die Patienten in der Behandlungsgruppe erhielten über einen Zeitraum von drei Monaten 25 mg Zink pro Tag, die Kontrollgruppe erhielt keine Studien-Medikation. Untersucht wurde die Hypsomie bei Studieneinschluss und –abschluss nach drei Monaten mit Hilfe des Sniffin’ Sticks-Riechtest, bestehend aus drei Subtests zur Bestimmung der Riechschwelle, der Diskriminations- und Identifikationsleistung. Hauptzielkriterium der Studie war die Änderung der Identifikationsleistung nach drei Monaten. Nebenzielkriterien waren die Änderung der Riechschwelle und des Diskriminationsvermögens, ebenso die Differenzen bezüglich der motorischen Symptomatik bestimmt anhand des UPDRS II und III sowie einer dreidimensionalen, ultraschallgestützten Bewegungsanalyse (Fa. Zebris). Des weiteren erfolgte eine Bestimmung des Zinkspiegels im Serum und ein Test zur Detektion eines funktionellen Zinkmangels. Zum Ausschluss anderer Ursachen einer Riechstörung wurde eine Rhinoskopie durchgeführt. Die Analyse der Daten ergab, dass es weder in der Kontroll-, noch in der Behandlungsgruppe zu einer signifikanten Veränderung der Hyposmie kam. Auch bezüglich der Nebenzielkriterien wurden keine signifikanten Veränderungen erzielt. Diese Ergebnisse legen nahe, dass a) Zink keine vielversprechende Therapieoption der Hyposmie bei Morbus Parkinson ist, b) die Hyposmie bei Morbus Parkinson nicht kausal mit Zinkmangel assoziiert ist und c) Zink keine effektive Behandlung bezüglich der motorischen Symptomatik darstellt

Kompetenznetz Parkinson Abschlussbericht der 1. Foerderperiode

SIGLEAvailable from TIB Hannover: F03B1158+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung und Forschung, Berlin (Germany); DLR Deutsches Zentrum fuer Luft- und Raumfahrt e.V., Bonn (Germany)DEGerman