Krankenanstalt Rudolfstiftung

Vienna, Austria

Krankenanstalt Rudolfstiftung

Vienna, Austria

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Finsterer J.,Krankenanstalt Rudolfstiftung
European Journal of Paediatric Neurology | Year: 2010

Treatment of mitochondrial disorders (MIDs) is a challenge since there is only symptomatic therapy available and since only few randomized and controlled studies have been carried out, which demonstrate an effect of some of the symptomatic or supportive measures available. Symptomatic treatment of MIDs is based on mainstay drugs, blood transfusions, hemodialysis, invasive measures, surgery, dietary measures, and physiotherapy. Drug treatment may be classified as specific (treatment of epilepsy, headache, dementia, dystonia, extrapyramidal symptoms, Parkinson syndrome, stroke-like episodes, or non-neurological manifestations), non-specific (antioxidants, electron donors/acceptors, alternative energy sources, cofactors), or restrictive (avoidance of drugs known to be toxic for mitochondrial functions). Drugs which more frequently than in the general population cause side effects in MID patients include steroids, propofol, statins, fibrates, neuroleptics, and anti-retroviral agents. Invasive measures include implantation of a pacemaker, biventricular pacemaker, or implantable cardioverter defibrillator, or stent therapy. Dietary measures can be offered for diabetes, hyperlipidemia, or epilepsy (ketogenic diet, anaplerotic diet). Treatment should be individualized because of the peculiarities of mitochondrial genetics. Despite limited possibilities, symptomatic treatment should be offered to MID patients, since it can have a significant impact on the course and outcome. © 2009 European Paediatric Neurology Society.


Finsterer J.,Krankenanstalt Rudolfstiftung
Journal of the Neurological Sciences | Year: 2011

Mitochondrial disorders (MIDs) occasionally manifest as polyneuropathy either as the dominant feature or as one of many other manifestations (inherited mitochondrial neuropathy). MIDs in which polyneuropathy is the dominant feature, include NARP syndrome due to the transition m.8993T>, CMT2A due to MFN2 mutations, CMT2K and CMT4A due to GDAP1 mutations, and axonal/demyelinating neuropathy with external ophthalmoplegia due to POLG1 mutations. MIDs in which polyneuropathy is an inconstant feature among others is the MELAS syndrome, MERRF syndrome, LHON, Mendelian PEO, KSS, Leigh syndrome, MNGIE, SANDO; MIRAS, MEMSA, AHS, MDS (hepato-cerebral form), IOSCA, and ADOA syndrome. In the majority of the cases polyneuropathy presents in a multiplex neuropathy distribution. Nerve conduction studies may reveal either axonal or demyelinated or mixed types of neuropathies. If a hereditary neuropathy is due to mitochondrial dysfunction, the management of these patients is at variance from non-mitochondrial hereditary neuropathies. Patients with mitochondrial hereditary neuropathy need to be carefully investigated for clinical or subclinical involvement of other organs or systems. Supportive treatment with co-factors, antioxidants, alternative energy sources, or lactate lowering agents can be tried. Involvement of other organs may require specific treatment. Mitochondrial neuropathies should be included in the differential diagnosis of hereditary neuropathies. © 2011 Elsevier B.V.


Finsterer J.,Krankenanstalt Rudolfstiftung | Kothari S.,NIMHANS
International Journal of Cardiology | Year: 2014

Objectives One of the most frequently affected organs in mitochondrial disorders (MIDs), defined as hereditary diseases due to affection of the mitochondrial energy metabolism, is the heart. Cardiac involvement (CI) in MIDs has therapeutic and prognostic implications. This review aims at summarizing and discussing the various cardiac manifestations in MIDs.Methods Data for this review were identified by searches of MEDLINE, Current Contents, and PubMed using appropriate search terms.Results CI in MIDs may be classified according to various different criteria. In the present review cardiac abnormalities in MIDs are discussed according to their frequency with which they occur. CI in MIDs includes cardiomyopathy, arrhythmias, heart failure, pulmonary hypertension, dilation of the aortic root, pericardial effusion, coronary heart disease, autonomous nervous system dysfunction, congenital heart defects, or sudden cardiac death. The most frequent among the cardiomyopathies is hypertrophic cardiomyopathy, followed by dilated cardiomyopathy, and noncompaction.Conclusions CI in MID is more variable and prevalent than previously thought. All tissues of the heart may be variably affected. The most frequently affected tissue is the myocardium. MIDs should be included in the differential diagnoses of cardiac disease. © 2014 Elsevier Ireland Ltd. All rights reserved.


Stollberger C.,Krankenanstalt Rudolfstiftung | Finsterer J.,Steingasse 31 18
Drugs and Aging | Year: 2013

The prevalence of atrial fibrillation (AF) and the embolic risk increase with age. Elderly AF patients are undertreated with vitamin K antagonists (VKA). The new oral anticoagulants (NOAC) dabigatran, rivaroxaban and apixaban have been shown to be non-inferior to VKA for stroke prevention in AF. We summarize the knowledge about primary and secondary stroke prevention by NOAC in AF patients>75 years of age. A literature search was carried out using the terms 'dabigatran', 'rivaroxaban', 'apixaban', 'elderly', 'octogenarians', 'atrial fibrillation' and 'anticoagulation' from 1998 to 2013. Randomized clinical trials, longitudinal studies, case series and case reports were included. Whereas studies investigating the use of VKA for stroke prevention in the 1990s were carried out by industry-independent institutions, all NOAC-investigating trials were sponsored by the manufacturers of the respective drugs. Frail elderly people were not represented in NOAC-investigating trials because of various exclusion criteria, and only one-third of patients were aged >75 years. A subgroup analysis from the dabigatraninvestigating trial indicated that elderly patients might have a higher risk for extracranial bleeding complications with NOAC than with VKA. Further concerns about the use of NOAC in the elderly are the high prevalence of renal insufficiency in AF patients>75 years of age, the largely unknown risk of drug-drug and drug-food interactions, the lack of easily available laboratory monitoring tests of anticoagulant activity and the lack of an antidote. There is a need for independent studies comparing the efficacy and risk of side effects of NOAC with that of VKA in elderly AF patients ©Springer International Publishing Switzerland 2013.


Finsterer J.,Krankenanstalt Rudolfstiftung
Journal of the Neurological Sciences | Year: 2010

Kennedy's disease, also known as bulbospinal muscular atrophy (BSMA), is a rare, adult-onset, X-linked, recessive trinucleotide, polyglutamine (poly-G) disorder, caused by expansion of an unstable CAG-tandem-repeat in exon 1 of the androgen-receptor (AR) gene on chromosome Xq11-12. Poly-Q-expanded AR accumulates in nuclei, undergoes fragmentation and initiates degeneration and loss of motor neurons and dorsal root ganglia. Phenotypically, patients present with weakness and wasting of the facial, bulbar and extremity muscles, sensory disturbances, and endocrinological disturbances, such as gynecomastia and reduced fertility. In the limb muscles weakness and wasting may be symmetric or asymmetric, proximal or distal, or may predominate at the lower or upper limb muscles. There may be mild to severe hyper-CK-emia, elevated testosterone or other sexual hormones, abnormal motor and sensory nerve conduction studies, and neuropathic or rarely myopathic alterations on muscle biopsy. BSMA is diagnosed if the number of CAG-repeats exceeds 40. No causal therapy is available but symptomatic therapy may be beneficial for weakness, tremor, endocrinological abnormalities, muscle cramps, respiratory failure, or dysphagia. The course is slowly progressive and the ability to walk lost only late in life. Only few patients require ventilatory support and life expectancy is only slightly compromised. © 2010 Elsevier B.V.


Finsterer J.,Krankenanstalt Rudolfstiftung | Frank M.,Krankenanstalt Rudolfstiftung
Current Opinion in Hematology | Year: 2013

PURPOSE OF REVIEW: This review highlights recent advances concerning pathogenesis, clinical presentation, diagnosis and treatment of Barth syndrome with particular regard to haematological abnormalities (e.g., neutropenia). RECENT FINDINGS: Directed motility and killing activity of neutrophils is normal in patients with Barth syndrome, but neutrophils and eospinophils show phosphatidylserine exposure without exhibiting other markers of apoptosis. Apparently, neutropenia does not result from apoptosis of myeloid precursors or end-stage neutrophils but from reactive oxygen species triggered exposure of phosphatidylserine, leading to increased clearance of neutrophils by tissue macrophages. Lymphoblasts of patients with Barth syndrome show increased variability of mitochondrial size and increased mitochondrial mass due to increased clustering of fragmented mitochondria inside nuclear invaginations. Lymphoblast mitochondria show reduced cristae density, reduced cristae alignment and heterogenous cristae distribution. Areas of adhesion of opposing inner membranes result in obliteration of the inter-cristae space. Short or extended adhesion zones result in sheets of collapsed cristae, which are packaged as multiple concentric layers. In single patients, neutropenia may favourably respond to biweekly injections of granulocyte colony stimulating factor. SUMMARY: Neutropenia in Barth syndrome is most likely due to reactive oxygen species induced exposure of phosphatidylserine, leading to increased clearance of neutrophils by tissue macrophages. In single patients, application of granulocyte colony stimulating factor may resolve neutropenia in Barth syndrome. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Finsterer J.,Krankenanstalt Rudolfstiftung | Burgunder J.-M.,University of Bern
European Journal of Medical Genetics | Year: 2014

Background: Genetic background and pathogenesis of motor neuron diseases (MNDs) have been increasingly elucidated over recent years. Aims: To give an overview about publications during the last year concerning the genetic background and phenotypic manifestations of MNDs, such as familial or sporadic amyotrophic lateral sclerosis (fALS, sALS), spinal muscular atrophies (SMA), bulbospinal muscular atrophy (BSMA), and unclassified MNDs. Methods: Pubmed search for literature about ALS, SMA, and BSMA for the period 10/2012 to 9/2013. Results: An increasing number of mutated genes is recognised in fALS but also sALS patients. Genes mutated in sALS include C9orf72, SOD1, TARDBP, FUS, UBQL2, SQSTM1, DCTN1, and UNC13A. Juvenile (onset <20. y) and adult ALS (early onset 20-60. y, late onset >60. y) are differentiated. Juvenile fALS is most frequently caused by mutations in ALS2, SETX, spatacsin, or Sigmar1 and adult fALS by mutations in C9orf72, SOD1, TARDBP, and FUS. Onset, phenotype, progression, and outcome of ALS are variable between different mutations, different genes, and different countries. Differentiation between sALS and fALS cases becomes artificial. Conclusions: Further progress has been made over the last year in the clarification and understanding of the aetiology and pathogenesis of MNDs. However, further effort is needed to answer the many remaining questions. © 2014 Elsevier Masson SAS.


Finsterer J.,Krankenanstalt Rudolfstiftung
BMC Musculoskeletal Disorders | Year: 2012

Background: Biomarkers of peripheral muscle fatigue (BPMFs) are used to offer insights into mechanisms of exhaustion during exercise in order to detect abnormal fatigue or to detect defective metabolic pathways. This review aims at describing recent advances and future perspectives concerning the most important biomarkers of muscle fatigue during exercise. Results: BPMFs are classified according to the mechanism of fatigue related to adenosine-triphosphate- metabolism, acidosis, or oxidative-metabolism. Muscle fatigue is also related to an immunological response. impaired calcium handling, disturbances in bioenergetic pathways, and genetic responses. The immunological and genetic response may make the muscle susceptible to fatigue but may not directly cause muscle fatigue. Production of BPMFs is predominantly dependent on the type of exercise. BPMFs need to change as a function of the process being monitored, be stable without appreciable diurnal variations, correlate well with exercise intensity, and be present in detectable amounts in easily accessible biological fluids. The most well-known BPMFs are serum lactate and interleukin-6. The most widely applied clinical application is screening for defective oxidative metabolism in mitochondrial disorders by means of the lactate stress test. The clinical relevance of most other BPMFs, however, is under debate, since they often depend on age, gender, physical fitness, the energy supply during exercise, the type of exercise needed to produce the BPMF, and whether healthy or diseased subjects are investigated. Conclusions: Though the role of BPMFs during fatigue is poorly understood, measuring BPMFs under specific, standardised conditions appears to be helpful for assessing biological states or processes during exercise and fatigue. © 2012 Finsterer; licensee BioMed Central Ltd.


Finsterer J.,Krankenanstalt Rudolfstiftung | Cripe L.,Nationwide Childrens Hospital
Nature Reviews Cardiology | Year: 2014

Treatment of cardiac disease in patients with dystrophinopathies substantially improves outcomes. In this Review, we summarize and discuss findings from the past 20 years and future perspectives for therapeutic options to treat cardiovascular disease in these patients. Their cardiac disease can be subclinical or symptomatic. Presymptomatic treatment with angiotensin- converting-enzyme inhibitors, angiotensin-II-receptor blockers, β-blockers, or mineralocorticoid-receptor antagonists is a well-established method to delay the clinical manifestations of cardiac disease. Treatment of patients with dystrophinopathy and symptomatic cardiac disease, such as heart failure or arrhythmia, follows well-established guidelines for the general treatment of cardiac disease. These treatments improve outcomes, particularly when supported by noncardiovascular measures in the advanced stages of cardiac involvement. Patients with dystrophinopathies and cardiac disease can also benefit from optimal management of scoliosis, noninvasive positive pressure ventilation, and from pain therapy. Molecular therapies for treating cardiac diseases in patients with dystrophinopathies are experimental, but promising. © 2014 Macmillan Publishers Limited. All rights reserved.


Finsterer J.,Krankenanstalt Rudolfstiftung
Acta Neurologica Belgica | Year: 2010

Cryptogenic stroke(CS) is defined as cerebral ischemia of obscure or unknown origin. The cause of CS remains undetermined because the event is transitory or reversible, investigations did not look for all possible causes, or because some causes truly remain unknown. One third of the ischemic strokes is cryptogenic. CS is more frequent in younger than older patients and most frequently due to cardiac embolism, followed by vasculopathy, and coagulopathy . The most frequent causes of cardiac embolism include paradoxical embolism from upstream veins via a patent foramen ovale(PFO), paroxysmal atrial-fibrillation, valvular heart-disease, and atrial septal aneurysm. The most frequent vascular causes of CS are complex aortic plaques and Fabry's disease. Diagnostic work-up for CS includes transesophageal echocardiography, long-term ECG-recordings, CT-/ MR-angiography of the aorta, transcranial Doppler-sonography, imaging for venous thrombosis in case of paradoxical embolism, and blood chemical investigations and coagulation tests. Recurrence rate and prognosis of CS is under debate. Primary and secondary stroke prevention in CS is notat variance from stroke of known cause. If the cause of CS can be identified, appropriate treatment is indicated. A PFO requires antiplatelet medication, OAC if there are other indications for OAC, and closure in case of recurrent CS under OAC.

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