Finsterer J.,Danube University Krems
Acta Neurologica Scandinavica | Year: 2012
Among the various central nervous system (CNS) manifestations of mitochondrial disorders (MIDs), cognitive impairment is increasingly recognized and diagnosed (mitochondrial cognitive dysfunction). Aim of the review was to summarize recent findings concerning the aetiology, pathogenesis, diagnosis and treatment of cognitive decline in MIDs. Among syndromic MIDs due to mitochondrial DNA (mtDNA) mutations, cognitive impairment occurs in patients with mitochondrial encephalopathy, lactic acidosis and stroke-like episodes syndrome, myoclonus epilepsy with ragged-red fibres syndrome, mitochondrial chronic progressive external ophthalmoplegia, Kearns-Sayre syndrome, neuropathy, ataxia and retinitis pigmentosa syndrome and maternally inherited diabetes and deafness. Among syndromic MIDs due to nuclear DNA (nDNA) mutations, cognitive decline has been reported in myo-neuro-gastro-intestinal encephalopathy, mitochondrial recessive ataxia syndrome, spinocerebellar ataxia with encephalopathy, Mohr-Tranebjaerg syndrome, leuko-encephalopathy; brain and spinal cord involvement and lactic acidosis, CMT2, Wolfram syndrome, Wolf-Hirschhorn syndrome and Leigh syndrome. In addition to syndromic MIDs, a large number of non-syndromic MIDs due to mtDNA as well as nDNA mutations have been reported, which present with cognitive impairment as the sole or one among several other CNS manifestations of a MID. Delineation of mitochondrial cognitive impairment from other types of cognitive impairment is essential to guide the optimal management of these patients. Treatment of mitochondrial cognitive impairment is largely limited to symptomatic and supportive measures. Cognitive impairment may be a CNS manifestation of syndromic as well as non-syndromic MIDs. Correct diagnosis of mitochondrial cognitive impairment is a prerequisite for the optimal management of these patients. © 2012 John Wiley & Sons A/S.
Finsterer J.,Danube University Krems
European Journal of Neurology | Year: 2011
Central nervous system (CNS) manifestations of mitochondrial disorders (MIDs) are accessible to therapy. Therapy of CNS abnormalities may be categorized as acting on the pathogenic cascade or on the genetic level, which is experimental. Treatment acting on the pathogenic cascade may be classified as non-specific, including antioxidants, electron donors/acceptors, lactate-lowering agents, alternative energy providers, cofactors, avoidance of mitochondrion-toxic drugs, and physiotherapy, or as specific, including drugs against epilepsy, movement disorders, migraine, spasticity, psychiatric abnormalities, hypopituitarism, or bulbar manifestations, ketogenic diet, deep brain stimulation, or artificial ventilation. Stroke-like episodes need to be delineated from ischaemic stroke and require special management. Potentially, mitochondrion-toxic drugs and drug cocktails need to be avoided, seizures should be consequently treated even with mitochondrion-toxic drugs if necessary, and as few drugs as possible should be given. Effective treatment acting on the pathogenic cascade may increase the quality of life and outcome in patients with MID and may prevent a therapeutic nihilism occasionally upcoming with MIDs. © 2010 The Author(s). European Journal of Neurology © 2010 EFNS.
Finsterer J.,Danube University Krems
Advances in Experimental Medicine and Biology | Year: 2012
Though inherited mitochondrial disorders (MIDs) are most well known for their syndromic forms, for which widely known acronyms (MELAS, MERRF, NARP, LHON etc.) have been coined, the vast majority of inherited MIDs presents in a non-syndromic form. Since MIDs are most frequently multisystem disorders already at onset or during the disease course, a MID should be suspected if there is a combination of neurological and non-neurological abnormalities. Neurological abnormalities occurring as a part of a MID include stroke-like episodes, epilepsy, migraine-like headache, movement disorders, cerebellar ataxia, visual impairment, encephalopathy, cognitive impairment, dementia, psychosis, hypopituitarism, aneurysms, or peripheral nervous system disease, such as myopathy, neuropathy, or neuronopathy. Non-neurological manifestations concern the ears, the endocrine organs, the heart, the gastrointestinal tract, the kidneys, the bone marrow, and the skin. Whenever there is an unexplained combination of neurological and non-neurological disease in a patient or kindred, a MID should be suspected and appropriate diagnostic measures initiated. Genetic testing should be guided by the phenotype, the biopsy findings, and the biochemical results. © 2012 Springer Science+Business Media B.V.
Finsterer J.,Danube University Krems |
Blazek G.,Hanusch Krankenhaus
International Journal of Cardiology | Year: 2013
Background: Left-ventricular hypertrabeculation/noncompaction(LVHT) is a cardiac abnormality of unknown aetiology, frequently associated with arrhythmias, heart failure, and embolism. In most cases LVHT is associated with neuromuscular disorders (NMDs) or other rare non-neuromuscular genetic syndromes. Occasionally, LVHT occurs familiarly. Methods and results: Invited for a cardiologic investigation were all first-degree relatives of index patients with LVHT who attended the cardiologic department. Altogether 25 relatives of 15 index patients from 15 families were investigated. Three members each were investigated in 3 families, 2 patients each in 4 families and 1 member each in 8 families. Among the 25 relatives from the 15 families, LVHT was found in 4 of them. Accordingly, familial LVHT was detected in 4 of the 15 investigated families (27%). Among the 4 relatives with LVHT, extension and morphology were similar to the appropriate index patient in 2 families. A NMD was diagnosed in three of the four relatives (75%) with familial LVHT. One relative without LVHT presented with a history of Fallot's tetralogy, and two relatives each presented with thickening of the left-ventricular myocardium. Conclusions: LVHT is familial in at least 27% of the patients with LVHT. LVHT may differ between relatives in some of the patients with familial LVHT. Familial LVHT is associated with a NMD in the majority of the cases. Relatives of LVHT patients may present with cardiac abnormalities other than LVHT. © 2011 Elsevier Ireland Ltd. All rights reserved.
Thaler K.,Danube University Krems
Cochrane database of systematic reviews (Online) | Year: 2011
Seasonal affective disorder (SAD) is a seasonal pattern of recurrent depressive episodes that is often treated with second-generation antidepressants (SGAs), light therapy or psychotherapy. To assess the efficacy and safety of SGAs for the treatment of SAD in adults in comparison with placebo, light therapy, other SGAs or psychotherapy. We searched the Cochrane Depression, Anxiety and Neuorosis Review Group's specialised register (CCDANCTR) on the 26 August 2011. The CCDANCTR contains reports of relevant randomised controlled trials from The Cochrane Library (all years), EMBASE (1974 to date), MEDLINE (1950 to date) and PsycINFO (1967 to date). In addition, we searched pharmaceutical industry trials registers via the Internet to identify unpublished trial data. Furthermore, we searched OVID MEDLINE, MEDLINE In-process, EMBASE and PsycINFO to 27July 2011 for publications on adverse effects (including non-randomised studies). For efficacy we included randomised trials of SGAs compared with other SGAs, placebo, light therapy or psychotherapy in adult participants with SAD. For adverse effects we also included non-randomised studies. Two review authors screened abstracts and full-text publications against the inclusion criteria. Data abstraction and risk of bias assessment were conducted by one reviewer and checked for accuracy and completeness by a second. We pooled data for meta-analysis where the participant groups were similar and the studies assessed the same treatments with the same comparator and had similar definitions of outcome measures over a similar duration of treatment. For efficacy we included three randomised trials of between five and eight weeks duration with a total of 204 participants. For adverse effects we included two randomised trials and three observational (non-randomised) studies of five to eight weeks duration with a total of 225 participants. Overall, the randomised trials had low-to-moderate risk of bias, and the observational studies had a high risk of bias (due to small size and high attrition). The participants in the studies all met DSM (Diagnostic and Statistics Manual of Mental Disorders) criteria for SAD. The average age was approximately 40 years and 70% of the participants were female.Results from one trial with 68 participants showed that fluoxetine was not significantly more effective than placebo in achieving clinical response (risk ratio (RR) 1.62, 95% confidence interval (CI) 0.92 to 2.83). The number of adverse effects were similar between the two groups.We located two trials that contained a total of 136 participants for the comparison fluoxetine versus light therapy. Our meta-analysis of the results of the two trials showed fluoxetine and light therapy to be approximately equal in treating seasonal depression: RR of response 0.98 (95% CI 0.77 to 1.24), RR of remission 0.81 (95% CI 0.39 to 1.71). The number of adverse effects was similar in both groups.Two of the three randomised trials and three non-randomised studies contained adverse effect data on 225 participants who received fluoxetine, escitalopram, duloxetine, reboxetine, light therapy or placebo. We were only able to obtain crude rates of adverse effects, so any interpretation of this needs to be undertaken with caution. Between 22% and 100% of participants who received a SGA suffered an adverse effect and between 15% and 27% of participants withdrew from the studies because of adverse effects. Evidence for the effectiveness of SGAs is limited to one small trial of fluoxetine compared with placebo, which shows a non-significant effect in favour of fluoxetine, and two small trials comparing fluoxetine against light therapy, which suggest equivalence between the two interventions. The lack of available evidence precludes the ability to draw any overall conclusions on the use of SGAs for SAD. Further larger RCTs are required to expand and strengthen the evidence base on this topic, and should also include comparisons with psychotherapy and other SGAs.Data on adverse events were sparse, and a comparative analysis was not possible. Therefore the data we obtained on adverse effects is not robust and our confidence in the data is limited. Overall, up to 27% of participants treated with SGAs for SAD withdrew from the studies early due to adverse effects. The overall quality of evidence in this review is very low.