1,720,971 research outputs found
Current and emerging treatment options in the management of Friedreich ataxia
No full textMichelangelo Mancuso, Daniele Orsucci, Anna Choub, Gabriele SicilianoDepartment of Neuroscience, Neurological Clinic, University of Pisa, Pisa, ItalyAbstract: Friedreich ataxia (FRDA) is the most common autosomal recessive ataxia. Oxidative damage within the mitochondria seems to have a key role in the disease phenotype. Therefore, FRDA treatment options have been mostly directed at antioxidant protection against mitochondrial damage. Available evidence seems to suggest that patients with FRDA should be treated with idebenone, because it is well tolerated and may reduce cardiac hypertrophy and, at higher doses, also improve neurological function, but large controlled clinical trials are still needed. Alternatively, gene-based strategies for the treatment of FRDA may involve the development of small-molecules increasing frataxin gene transcription. Animal and human studies are strongly needed to assess whether any of the potential new treatment strategies, such as iron-chelating therapies or treatment with erythropoietin or histone deacetylase inhibitors and other gene-based strategies, may translate into an effective therapy for this devastating disorder. In this review, we try to provide an answer to some questions related to current and emerging treatment options in the management of FRDA.Keywords: frataxin, idebenone, oxidative stres
Epilepsy and limb girdle muscular dystrophy type 2A: double trouble, serendipitous finding or new phenotype?
No full textAutosomal recessive limb girdle muscular dystrophies (LGMD) type 2A are a group of disorders characterised by progressive involvement of proximal limb girdle muscles and caused by changes in the CAPN3 gene. Involvement of tissues other than the skeletal muscle has not been reported so far. Here we describe the unusual association of LGMD2A and idiopathic generalised epilepsy in a 14-year-old girl
Psychiatric involvement in adult patients with mitochondrial disease.
No full textMitochondrial disorders are caused by impairment of the respiratory chain. Psychiatric features often represent part of their clinical spectrum. However, the real incidence of psychiatric disorders in these diseases is unknown. The aim of this study was to evaluate psychiatric involvement in a group of patients with mitochondrial disorders and without already diagnosed mental illness. Twenty-four patients with mitochondrial disorder and without already diagnosed mental diseases have been studied by means of the mini-international neuropsychiatric interview (MINI) and the newcastle mitochondrial diseases adult scale (NMDAS). In patients with mitochondrial disease, psychiatric conditions were far more common than in general Italian population (about 60 vs. 20-25%), and included major depression, agoraphobia and/or panic disorder, generalized anxiety disorder, social anxiety disorder, psychotic syndromes. Psychiatric involvement did not seem to depend on disease progression. Large, multicenter studies are strongly needed to better characterize the natural history of mitochondrial disorders and of their psychiatric involvement. Moreover, the possibility of mitochondrial diseases should be considered in patients with psychiatric diseases. Finally, we encourage psychiatric evaluation as a routinary approach to mitochondrial patients
Coenzyme Q10 and neurological diseases: An update
No full textCoenzyme Q10 (CoQ10) is a vitamin-like substance used in the treatment of several disorders including mitochondrial and neurodegenerative diseases. CoQ10 is a safe supplement with minimal side effects and low drug interaction potential. Here we review the clinical data on safety and efficacy of CoQ10 in neurological diseases. © 2006 Bentham Science Publishers Ltd
Mitochondria, cognitive impairment, and Alzheimer's disease.
Full text linkTo date, the beta amyloid (Abeta) cascade hypothesis remains the main pathogenetic model of Alzheimer's disease (AD), but its role in the majority of sporadic AD cases is unclear. The "mitochondrial cascade hypothesis" could explain many of the biochemical, genetic, and pathological features of sporadic AD. Somatic mutations in mitochondrial DNA (mtDNA) could cause energy failure, increased oxidative stress, and accumulation of Abeta, which in a vicious cycle reinforce the mtDNA damage and the oxidative stress. Despite the evidence of mitochondrial dysfunction in AD, no causative mutations in the mtDNA have been detected so far. Indeed, results of studies on the role of mtDNA haplogroups in AD are controversial. In this review we discuss the role of the mitochondria, and especially of the mtDNA, in the cascade of events leading to neurodegeneration, dementia, and AD
Diagnostic Approach to Mitochondrial Disorders: the Need for a Reliable Biomarker
No full textMitochondrial diseases (MD) are disorders caused by impairment of the mitochondrial electron transport chain (ETC). Phenotypes are polymorphous and may range from pure myopathy to multisystemic disorders. The genetic defect can be located on mitochondrial or nuclear DNA. The ETC is needed for oxidative phosphorylation (which provides the cell with the most efficient energetic outcome in terms of ATP production), and consists of five multimeric protein complexes located in the inner mitochondrial membrane. The ETC also requires cytochrome c and a small electron carrier, coenzyme Q10. One of the pathogenic mechanisms of ETC disorders is excessive accumulation of reactive oxygen species (ROS). Mitochondrial dysfunction and oxidative stress appear to have a strong impact also on the pathogenesis of neurodegenerative diseases. At present, diagnosis of MD requires a complex approach: measurement of serum lactate, exercise testing, electromyography, magnetic resonance spectroscopy, muscle histology and enzymology, and genetic analysis. Biomarkers are molecules associated with biological processes or regulatory mechanisms. A reliable biomarker for the screening or diagnosis of MD is still needed. In this paper we review the diagnostic approach to MD, from serum lactate to other blood and urinary markers, from muscular biopsy to imaging studies, and we highlight some potentially interesting perspectives in this field
Residual insomnia in patients with restless legs syndrome after treatment
No full textPatients with Restless Legs Syndrome (RLS) after the treatment still present residual insomnia
than can emerge in follow up visits: about 5% of patients treated manifests symptoms of
insomnia that can persist after one year. A differential diagnosis with an inadequate treatment
Abstracts 51
of RLS or augmentation should be done. Moreover, comorbidity with other sleep disturbance
like Obstructive Sleep Apnea Syndrome (OSAS) or with general medical conditions such as
chronic renal insufficiency has to be considered and properly treated. As far as the treatment
of residual insomnia is concerned, it has to be underlined that SSRI can foster the worsening
of RLS symptoms, while the use of trazodone and benzodiazepines can be more appropriate
and helpfull in such clinical conditions. Furthermore, the use of psychotherapy for the
treatment of insomnia can be extremely important, in particular if we consider the limits of
pharmacological intervention described abov
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