Recommendations for the use of prolonged-release fampridine in patients with multiple sclerosis (MS).

Prolonged-release fampridine (fampridine PR) is a potassium channel blocker that improves conductivity of signal on demyelinated axons in central nervous system. Fampridine PR has been approved to improve speed of walking in patients with multiple sclerosis. This statement provides a brief summary of data on fampridine PR and recommendations on practical use of the medication in clinical practice, prediction, and evaluation of response to treatment and patient management.

Epilepsy in adult X-linked adrenoleucodystrophy due to the deletion c.1415-1416delAG in exon 5 of the ABCD1-gene.

Seizures in cerebral X-linked adrenoleucodystrophy (X-ALD) more frequently occur in the early-onset compared to the late-onset form. Here we describe an adult in whom X-ALD deteriorated after head trauma and who developed epilepsy with progression of X-ALD. In a 50 year-old Caucasian male, cerebral X-ALD was diagnosed upon progressive gait disturbance, intellectual decline, elevated very-long chain fatty acids in the serum or leucocytes, cerebral MRI, showing extensive, symmetric, homogenous demyelination in the parieto-occipital areas, the splenium corporis callosum, the thalamus, the crura cerebri, the brain stem, and the pedunculi cerebelli, and the deletion c.1415-1416delAG in the ABCD1-gene. After a head trauma the phenotype deteriorated to mutism, dysphagia, and severe spastic quadruparesis. At an age of 50 years the patient experienced his first, self-limiting, tonic-clonic seizure during an infection, which is why valproic acid was started. Recurrence of seizures after discharge required repeated adaptation of the valproic acid-dosage. Adult X-ALD may be associated with late-onset seizures, which respond favourably to valproic acid. Since any type of seizure episode in adult-onset cerebral X-ALD is usually followed by neurological decline, prophylactic treatment with antiepileptic drugs should be considered not only in early-onset but also in adult-onset epilepsy in X-ALD.

[Memantine for treatment of behavioural disturbances and psychotic symptoms in moderate to moderately severe Alzheimer dementia: a naturalistic study in outpatient services in Austria]. / Memantin in der Behandlung von Verhaltensauffälligkeiten und psychotischen Symptomen bei moderater bis mittelschwerer Alzheimer-Demenz: Eine naturalistische Studie im ambulanten Bereich in Osterreich.

We conducted an open, 16-week study on the efficacy of memantine on behavioral disturbances and psychotic symptoms in moderate to moderately severe Alzheimer s disease in daily routine. Fifty-three patients of 20 outpatient centers in Austria were recruited. The Neuropsychiatric Inventory (NPI) was defined as main outcome measure. After 16 weeks the total NPI score improved by 4,6 points (p<0.01). The caregiver distress score was also significantly reduced. The most pronounced improvements were seen in the NPI components depression (-24,6%), aberrant motor behavior (-16,9%), agitation/agression, fear, apathy, disinhibition and disturbances in appetite and eating behavior (-11,3%, each). Our naturalistic study is in line with the results of controlled trials in moderate and severe Alzheimer dementia stages. Controlled clinical trials which have behavioral disturbances and psychotic symptoms as primary endpoint are needed to define the true potential of memantine in mild dementia stages.

[WHO Polio Eradication Programme:Status quo and implementation in Austria]. / WHO-Eradikationsprogramm für Poliomyelitis: Status quo und Umsetzung in Osterreich.

In 1988 the 41(th) World Health Assembly declared polio to be worldwide eradicated until the year 2000. Although this ambitious aim could not be reached completely, the yearly worldwide incidence was reduced by 99% and three WHO-Regions were declared polio-free (Americans, West Pacific, Europe). To maintain this status the following measures have to be carried out: polio vaccination, enterovirus surveillance, AFP-surveillance, quality control of laboratories and notification of labs keeping stocks of polio wildvirus. Especially after the Second World War Austria faced severe polio epidemics and thus general and free of charge polio vaccination for children and young adults up to 21 years was started in winter 1961/62 by the Austrian Ministry of Health (MoH). Immediately the yearly incidence dropped from 3.65/100.000 (n = 292) in 1961 to 0.1/100.000 (n = 8) in 1962. Since 1998 all mandatory national measures according the WHO polio eradication programme have been performed. Despite the worldwide success of the programme there are currently still four countries with endemic polio and since November 2006 eleven further countries have faced epidemics due to imported cases. Therefore the 60(th) World Health Assembly in 2007 again pointed to the threat of failing worldwide polio eradication. Currently the Global Polio Eradication Initiative (GPEI) works intensively with the concerned countries to fight against this development.

The search for a balance between short and long-term treatment outcomes in multiple sclerosis.

Multiple sclerosis is a lifelong, immune-mediated progressive disorder. The early age of onset and the chronic nature of the disease with accumulation of physical disability, demand a long-term ("lifelong") management, including disease-modifying immunomodulatory therapies and symptomatic treatments. The ultimate goal in the long-term management of multiple sclerosis is to prevent or delay the appearance of permanent neurological disability. Due to improvements in the diagnosis of multiple sclerosis, it is now possible to initiate treatment early in the disease process. To this end, first-line immunomodulatory treatments such as glatiramer acetate and beta-interferons are available that reduce the rate of relapses and disease activity as measured with magnetic resonance imaging. However, the short duration of clinical trials provides little information about long-term changes in disability over time. In the case of glatiramer acetate, a long-term, openlabel extension of the pivotal trial has provided prospective data on systematic regular follow-up of all patients who had ever received the drug during the original trial or its extension. Of 232 patients analysed, 108 were still participating in the study an average of ten years after treatment was initiated. Despite the limitations of open-label trials, this study has provided some evidence for a sustained reduction in frequency and severity of relapses and in the rate of accrual of disability. Such long-term data, which demonstrate safety, tolerability and sustained clinical benefit, help improve patient care and may contribute to patients taking a more positive view of treatment. Effective immunomodulatory treatment needs comprehensive information and education of the patient to establish long-term adherence, a critical determinant of long-term outcome. A multidisciplinary approach through a health care team is the optimal strategy, with encouragement to continue the therapy.

Costs and quality of life of multiple sclerosis in Austria.

This cost-of-illness analysis is part of a Europe-wide study on the costs of multiple sclerosis (MS) and is based on information from patients in Austria. The objective was to estimate the costs and quality of life (QOL) related to the level of disease severity and progression. Questionnaires were sent to 2995 patients registered with a nationwide patient organization. Patients were asked to provide details regarding the type of disease, relapses, level of functional disability, resource consumption (medical and non-medical), work absence, sick leave and informal care, as well as QOL. Surveys from a total of 1.019 (34.0%) patients were used in the analysis, of which the mean (standard deviation [SD]) age was 50 (12.2) years; 70% of patients were female. Patients with mild disease (Expanded Disability Status Scale [EDSS] score 0-3) represented 41% of patients, 36% had moderate disease (EDSS score 4-6.5) and 22% had severe disease (EDSS score > or =7). The mean (SD) EDSS score in the sample was 4.4 (2.4), with a mean (SD) utility of 0.55 (0.32). Costs are presented from the societal perspective as well as from the viewpoint of payers of care and invalidity. Mean total annual costs for an average patient in the sample were estimated at euro 40.300 in the societal perspective, whereas payers' costs were estimated at only half of this. Disease-modifying drugs represented a quarter of all costs in the payer perspective, but only 12% of societal costs. For society, the highest cost was the loss of productivity (36%), while payments for this loss (invalidity pensions and sick-leave compensation) accounted for only 21% of total costs to payers. Costs are highly correlated with disease progression, increasing four-fold from early disease to very severe disease (euro 16.000 to euro 63.800). Mean annual costs per patient reported are thus determined by the distribution of disease severity in the sample. Workforce participation decreases from roughly 75% in early disease to less than 10% in the late stages, despite the fact that 70% of patients with an EDSS score of 8 or 9 are still below the official retirement age. Consequently, productivity losses increase over fivefold. In parallel, costs of informal care increase from euro 325 per year at an EDSS score of 0-1 to over euro 20.000 at an EDSS score of 8-9. Hospitalization is very infrequent in early disease, representing less than euro 1.000 for patients with an EDSS score of 0-1, but increases steeply for patients with an EDSS score > or =5. QOL, measured as utility scores, decreases rapidly from almost 0.90 to 0.05 as disability becomes severe. However, the loss of utility is evident at all disease levels. Young patients with an EDSS score of approximately 2 have a utility that is 0.15 lower than matched individuals from the general population. This loss increases to approximately 0.4 for patients over 60 years of age with an average EDSS score of 6.0-6.5. Patients with a recent relapse had lower utility (-0.1) and higher costs (+ euro 4.750).

The Golden Agers and Tick-borne encephalitis. Conference report and position paper of the International Scientific Working Group on Tick-borne encephalitis.

The 7th meeting of the ISW TBE had the main topic "Tick-borne encephalitis in the Golden Agers". Data from 14 European countries were presented about incidence and clinical course of Tick borne encephalitis (TBE) in general and especially in the population over 50 years of age. With age immunity is impaired quantitatively and qualitatively, the reactions to vaccinations are generally slower, antibody titres reach lower values and decrease earlier. The incidence of the disease is increasing with age, also the clinical course is more severe, they suffer significantly more sequelae, need a longer rehabilitation and have a higher case fatality. Vaccination as the only efficient protection is needed in endemic areas, considering that mobility has increased very much. For the age group over 50 years regular booster vaccinations according to the recommended vaccination intervals or even shorter intervals are most important.

Efficacy of a neuropsychological training programme for patients with multiple sclerosis -- a randomised controlled trial.

BACKGROUND: One aim of this project was to investigate the efficacy of a specific training programme for MS patients which also contained compensation strategies and relaxation exercises relevant to everyday life. The other aim was to check the programme's relevance to everyday life. METHOD: 19 patients, randomised into two groups, took part in the study. The participants in the treated group completed a specific neurological training programme which began immediately after the basic testing (visit 1) and lasted 4 weeks, with a total of 12 sessions. The monitoring test was done immediately after the training programme (at visit 2) and the follow-up was 3 months later (visit 3). Both study groups were fully comparable as regards clinical and socio-demographic data and baseline intelligence level. RESULTS: The results of the cognitive training programme were especially evident in the significant improvements in executive functions (CKV) and spatial-constructional abilities (HAWIE-R). Comparison between the treated and the control group showed no significant difference in the fatigue values (MFIS). However, when the treated group was examined over the three times of measurements, the symptoms of fatigue had diminished significantly. Regarding memory, comparison of the groups showed no changes; within the treated group; however, the verbal (VLT) and nonverbal learning and memory (NVLT) improved significantly. The results for sustained attention improved in both groups over time. It must be assumed that a learning effect had occurred here. The depression values (BDI) also improved in both study groups. The follow-up questionnaire showed that 60% (6) attributed an average to above-average benefit to the training. CONCLUSION: To summarise, it is apparent that MS patients with mild to moderate cognitive impairment are able to profit from even a fairly brief neuropsychological training programme and to integrate much of it into their everyday lives. In view of this, it would seem appropriate to offer such a programme as standard, associated with medication.

Early fluoxetine treatment of post-stroke depression--a three-month double-blind placebo-controlled study with an open-label long-term follow up.

OBJECTIVE: Poststroke depression is a frequent psychiatric complication after stroke that may have strong negative impact on rehabilitation therapy and functional recovery. This study was conducted to show the efficacy and safety of early treatment with the selective serotonin reuptake inhibitor fluoxetine in post-stroke depressed patients. METHODS: This double-blind, randomized placebo-controlled study was of patients within two weeks after stroke. Moderate to severe depressed patients (determined by Hamilton Depression Scale (HDS) > 15, the Beck Depression Inventory (BDI) and the Clinical Global Impression (CGI) Scale) were randomized to receive either 20 mg/d fluoxetine or placebo for 3 months. Beside the psychiatric assessment, patients were evaluated by use of the Scandinavian Stroke Scale (SSS), the Mini-Mental-State-Examination (MMSE) and the Barthel-Index (BI). An open-label long-term follow up was done 18 months after the initial assessment. RESULTS: 54 depressed patients of an inpatient population of 242 consecutive stroke patients aged 25 to 85 years entered the trial within the first two weeks post-stroke. 50 patients completed the trial per-protocol. The initial severity of depression was comparable in the two groups (mean baseline HDS score 32.8 in the fluoxetine vs. 30.3 in the placebo group), as were neurological symptom severity and demographic parameters. Significant improvement was seen in both groups within 4 weeks of treatment, whereas no advantages of fluoxetine could be observed at this time. This indicates a high degree of spontaneous recovery during early rehabilitation therapy. BDI scores of patients treated with fluoxetine further decreased until the follow-up at 12 weeks, whereas the scores increased again in the placebo group. This depressive relapse of the placebo patients after the end of most rehabilitation efforts was evident at a long-term follow-up 18 months after inclusion, when patients who had been treated with fluoxetine were significantly less depressed. No side effects of fluoxetine treatment were detected. CONCLUSIONS: The advantages of fluoxetine were obvious at the follow-up 18 months after inclusion, but could not be demonstrated within the first three months of controlled treatment. The multitude of therapeutic efforts that take place in the early phase of rehabilitation might have facilitated spontaneous recovery from depression and might have hindered benefits of antidepressant treatment to become obvious. Fluoxetine treatment was well tolerated and safe.

Subacute brainstem angioencephalopathy: a case report and review of the literature.

A previously healthy 69-year-old man developed a progressive neurological illness with bulbar signs and ataxic paraparesis. Repeated MRI examinations revealed a large space occupying lesion in the lower brain stem with patchy contrast enhancement. MRI angiography was unremarkable and CSF had normal cell count but raised protein content. A brainstem tumor was suspected and a course of intravenous glucocorticosteroids was started. No improvement occurred and the patient died of pneumonia 11 weeks after onset. Neuropathology revealed confluent areas of complete or incomplete necrosis with marked edema in the lower brainstem. Predominantly venous meningeal vessels of the brainstem showed extensive fibromuscular thickening of all layers with luminal narrowing. In addition, intramural mononuclear infiltration was found. With the exception of localisation, this case exhibits all pathologic features of subacute diencephalic angioencephalopathy (SDAE), a rare fatal disease of unknown aetiology. In addition, the clinical features of typical age, male sex, disease duration and raised CSF proteins are shared. A common disease entity is suggested and the pathogenetic relevance of inflammation and venous outflow obstruction is discussed.

A controlled trial of tick-borne encephalitis vaccination in patients with multiple sclerosis.

The aim of this study was to investigate a possible link between a single vaccination against tick-borne encephalitis (TBE) and the appearance of one or more new cerebral lesions in magnetic resonance imaging (MRI) and/or a clinical relapse of MS. Fifteen MS patients with documented history of MS relapses living in a TBE endemic area were matched with 15 patients selected from a patient database containing 500 cases of MS. Three patients in each group were unvaccinated while all others had basic immunisation and regular booster vaccinations. Patients of the vaccination group received a single dose (3.3 microg) of a TBE vaccine. TBE antibodies were detected by ELISA and confirmed by neutralisation test. MRI was used as marker for disease activity and progression in addition to the clinical neurological examination. No association was seen between TBE vaccination and MRI detected disease activity, clinical relapse or disease progression of MS.