Gerthild Stiens

Aβ peptide1–42, Tau protein and S-100B protein level in cerebrospinal fluid of three patients with primary progressive aphasia

Abstract Primary progressive aphasia (PPA) is a clinical syndrome characterized by a slowly progressive aphasia in the absence of accompanying signs of generalized dementia. While non-fluent PPA tends to progress frontally and is usually linked to frontotemporal degeneration, fluent PPA might be associated with both, frontotemporal degeneration or Alzheimers disease. Although recent reports suggest that PPA belongs neuropathologically to the group of tauopathias, cerebrospinal fluid analysis has not been established as a means of diagnosis in PPA so far. In this paper we investigated Aβ peptide1–42 (Aβ1–42), Tau protein and S-100B protein level in the cerebrospinal fluid of three patients with PPA. In all patients Tau protein and S-100B level were slightly elevated, however, Aβ1–42 was found to be in normal range. Thus, our first results point to PPA being neurochemically linked to frontotemporal degeneration.

Treatment of restless legs syndrome with subcutaneous apomorphine in a patient with short bowel syndrome.

Sirs: The Restless Legs Syndrome (RLS) is characterised by dysaesthesia of the legs associated with an urge to move which occurs exclusively at rest and can be ameliorated by walking [2, 8]. There are primary and secondary forms of RLS. Primary RLS is often familial and the genetics of familial RLS are currently a topic of intense research. Secondary RLS may be drug-induced, e. g. due to antipsychotic or antiemetic treatment with dopamine antagonists. The aetiology of secondary RLS furthermore includes iron deficiency and uraemia as its two most common causes (for review, see Allen and Earley [1]). Therefore, patients with uraemia and renal anaemia due to terminal renal failure are particularly prone to develop secondary RLS. There are various treatment options: in secondary RLS, the underlying pathology should be identified and treated. This includes substitution of iron for iron deficiency anaemia and treatment of uraemia and uraemic anaemia in chronic renal failure with drugs, haemodialysis and ultimately renal transplantation. If causal treatment does not prove sufficient, there is a wide range of agents for symptomatic treatment, most of which require oral administration. These include levodopa, dopamine agonists, opioids, benzodiazepines, gabapentin and some other antiepileptic drugs [4, 5]. We report a 38-year old female patient with terminal renal failure and short bowel syndrome, who was admitted to our neurological clinic with an uncontrollable exacerbation of uraemic RLS. The past medical history of the patient included polycystic kidneys resulting in chronic renal failure with uraemia and renal anaemia, as well as familial polyposis coli, which had led to a total colectomy and a subtotal resection of the small intestine due to postoperative adhesions. She also suffered from severe malabsorption and therefore required chronic total parenteral nutrition via a venous port system. The patient first developed symptoms of RLS in 2001 when she became uraemic. Chronic haemodialysis treatment had to be started in 2002 but did not have a marked effect on her RLS symptoms. Concomitant treatment with erythropoietin was introduced in 2002 and the dose was consequently increased up to 4000 IU three times a week. This treatment regime led to normalisation of red blood cell count but RLS symptoms persisted and gradually became more severe. Therefore, additional symptomatic RLS treatment was initiated. Oral dosage with 300/ 75 mg levodopa/benserazide, 2.5 mg lorazepam, and up to 20 mg diazepam did not have any effect on the RLS symptoms and it was concluded that the patient did not benefit from this oral medication owing to her short bowel syndrome with malabsorption. Transdermally applied fentanyl at an initial dose of 25μg/h (Durogesic® patch) led to a marked reduction of symptoms. However, the therapeutic effect wore off in the course of several months and necessitated a dose increase of up to 150 μg/h and eventually no longer sufficiently controlled symptoms. The patient then suffered from severe sleep disturbances and difficulty in enduring haemodialysis. Therefore, subcutaneous injections of up to 30 mg of the opioid pirtramid were given additionally on demand. As symptoms became worse, in spite of high-dose opioid therapy, we decided to introduce subcutaneous injections of the potent dopamine-D1/D2 receptor agonist apomorphine. The initial dose of 0.5 mg did not have a sufficient therapeutic effect but led to nausea and vomiting. Antiemetic co-medication with 60 mg of oral domperidone solution consequently controlled the nausea. We then increased the dose of apomorphine to 1 mg, which controlled RLS symptoms sufficiently when applied at night time and additionally before each haemodialysis. The efficacy of apomorphine was reflected by a decrease of the severity score on the International Restless Legs Syndrome Rating Scale (IRLSRS [7]) from 37 points (i. e. very severe symptoms) to 20 points (i. e. moderate symptoms) and the patient felt very much relieved because she was now able to endure lying still for the haemodialysis procedure. She was trained in subcutaneous self-administration of apomorphine in order to minimise dependency on health care professionals. She also tolerated a reduction of fentanyl patches to 100 μg/h and a reduction of the dose and frequency of pirtramid injections (maximum daily dose now 15 mg) at discharge from hospital. Several days later, the patient presented again to our outpatients department with a severe relapse of symptoms. The history revealed that there had been a change in LETTER TO THE EDITORS

Filial maturity as a predictor for the burden of demented parents' caregivers.

SummaryIn this study, we administered the Louvain Filial Maturity Scale [Marcoen 1993] to 61 adult children of demented elderly. The scores of the seven factors of this scale were compared to the scores of an unselected group of adult children examined by Marcoen. The results were taken into the context with caregiver’s burden, and the effect of filial maturity on parents’ institutionalisation was investigated. Marcoen’s results were confirmed. Only the means of “filial help” and “parental consideration” differed slightly from the means of the unselected group. Overall, filial maturity had no influence on the caregiver’s feeling of burden, but higher “parental consideration” resulted in lower caregiver burden. In addition, adult children with more “filial obligation” continued to care for their parents in the community more often, even when experiencing great burden and stress. However, institutionalisation was caused mainly by parents’ growing needs and increasing behavioural problems. We conclude that “filial maturity” seems to be a very stable concept. Further investigations should focus on the relevance of the Louvain Filial Maturity Scale for caregiving relationship and also on the arrangement of the scale in order to exclude a “pseudo”-stability with regard to burdensome life events and situations.ZusammenfassungIn dieser Untersuchung wurde die Louvain Filial Maturity Scale bei 61 erwachsenen Kindern demenzkranker älterer Menschen eingesetzt. Die Scores der sieben Skalen der Louvain Filial Maturity Scale wichen nicht signifikant von denen der von Marcoen beschriebenen Gruppe ab. Die Ergebnisse wurden in den Kontext der Belastung von Pflegenden gestellt und der Effekt der filialen Reife auf die elterlichen Heimeinweisungen wurde untersucht. Trotz Abweichungen bei den Parametern „filiale Hilfe“ und „elterliche Wertschätzung“ wurden Marcoens Ergebnisse bestätigt. „Filiale Reife“ insgesamt hatte keinen Einfluss auf das Belastungsgefühl von Pflegenden, während eine höhere „elterliche Wertschätzung“ dieses Gefühl reduzierte. Außerdem behielten erwachsene Kinder mit größerem „filialen Verpflichtungsgefühl“ auch trotz eines hohen Belastungsgefühls die ambulante Pflege eher aufrecht. Wir halten „Filiale Reife“ für ein stabiles Konzept, die Louvain Filial Maturity Scale sollte weiter auf ihre Relevanz für Pflegebeziehungen untersucht werden.

Development of an International Schedule for the Assessment and Staging of Care for Dementia

BACKGROUND A reliable and valid global staging scale has been lacking within dementia care. OBJECTIVE To develop an easy-to-use multi-dimensional clinical staging schedule for dementia. METHODS The schedule was developed through: i) Two series of focus groups (40 and 48 participants, respectively) in Denmark, France, Germany, Netherlands, Spain, Switzerland, and UK with a multi-disciplinary group of professionals working within dementia care, to assess the need for a dementia-staging tool and to obtain suggestions on its design and characteristics; ii) A pilot-study over three rounds to test inter-rater reliability of the newly developed schedule using written case histories, with five members of the projects steering committee and 27 of their colleagues from Netherlands, France, and Spain as participants; and iii) A field-study to test the schedules inter-rater reliability in clinical practice in France, Germany, Netherlands, Spain, Italy, Turkey, South Korea, Romania, and Serbia, which included 209 dementia patients and 217 of their caregivers as participants. RESULTS Focus group participants indicated a clear need for a culture-fair international dementia staging scale and reached consensus on face validity and content validity. Accordingly, the schedule has been composed of seven dimensions including behavioral, cognitive, physical, functional, social, and care aspects. Overall, the schedule showed adequate face validity, content validity, and inter-rater reliability; in the nine field-sites, intraclass correlation coefficients (ICCs; absolute agreement) for individual dimensions ranged between 0.38 and 1.0, with 84.4% of ICCs over 0.7. ICCs for total sum scores ranged between 0.89 and 0.99 in the nine field-sites. CONCLUSION The IDEAL schedule looks promising as tool for the clinical and social management of people with dementia globally, though further reliability and validity testing is needed.

Clozapine-associated elevation of plasma cholinesterase

Objective The goal of this study was to identify adverse effects of the atypical neuroleptic clozapine on liver function and lipid metabolism. Methods Data which included serum levels of clozapine and its hepatic metabolite N-desmethyl clozapine were collected from medical records of patients treated with clozapine and controls. Results We identified a clozapine-associated marked elevation of plasma cholinesterase (ChE) with unchanged levels of AST, ALT or g-GT. ChE was correlated to the serum level of clozapine and even closer to N-desmethyl clozapine. For the total patient group we observed significant correlations of ChE with the body-mass index and body weight. However, clozapine-treated patients and controls did not differ with regard to body-mass index, triglycerides, and cholesterol. Conclusion We report for the first time a clozapine-associated and dose-dependent elevation of plasma ChE, which may be related to clozapine-associated effects on hepatic lipid metabolism or ChE enzyme induction.

P01-376 - Screening for dementia in very old age in primary care

Background There are many screening instruments available for the detection of dementia. However, they were not tested in very old age and often not in the primary care setting for which they are developed. Method We condensed a screening battery of all elements of common tests (MMSE, TFDD, DEMTECT, Clock Test…). Nine primary care practices took part in the study. The practice assistants were trained to approach all patients over 75y visiting the practice. Only patients with already diagnosed dementia, severe hearing or vision disability or communication deficits were excluded. After informed consent they applied the screening. Within the next days a second independent neuropsychological examination was arranged in the memory clinic of the University of Goettingen. This included established neuropsychological tests (CERAD-NP, WMS-R, TMT.) and further scales were applied (NPI, CDR..). All patients with CDR=0.5 were approached 1.5y later for a follow-up by phone. Results N=90 patients (25M, 65F) took part in the initial evaluation. From N=54 with CDR=0.5 only N=14 could be reached for follow-up. None of them returned to CDR=0, most progressed up to CDR=4. There were some correlations to education and dementia severity. All available screenings showed a good effect size of >0.70 (MMSE, DEMTECT, TFDD, RDST). Conclusion Elements for an optimal screening of the oldest old are discussed.