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Introduction: Eslicarbazepine acetate is a novel sodium channel blocker for use in the treatment of focal onset seizures. Prospective studies on its effectiveness in monotherapy in patients with newly diagnosed partial epilepsy in routine clinical practice are scarce., Aim: To evaluate the effectiveness of eslicarbazepine as initial monotherapy in patients with newly diagnosed partial epilepsy in routine clinical practice., Patients and Methods: A prospective, multicentre, post-authorisation study. Patients with newly diagnosed partial epilepsy aged 18 years or older without previous treatment were included. The efficacy variables were: percentage of seizure-free patients, responders and reduction in monthly frequency of seizures. The safety variables analyse the 12-month retention rate and the occurrence of adverse effects., Results: Fifty-three patients were included. The retention rate was 77.4%. At the end of the observation period, 83% of patients were seizure-free and 92.5% had reduced their baseline frequency by 50% or more. In addition, 68% of the patients reported some adverse effect and 7.5% of them dropped out of the study for this reason. The effectiveness analysis of the subgroup of patients aged 65 years or more showed no differences with respect to the overall population., Conclusion: Eslicarbazepine monotherapy in patients with newly diagnosed partial epilepsy, both in the general population and in the population over 65 years old, is effective and safe in routine clinical practice.

Introduction: Leigh syndrome is a neurodegenerative and progressive disease that appears usually in childhood due to defects in nuclear or mitochondrial genome. The mutation G14459A in mitochondrial DNA has been associated previously to Leber hereditary optic neuropathy and recently to Leigh syndrome., Case Report: A 10 months-old Mexican girl diagnosed of Leigh syndrome. Molecular-genetic studies detected the mutation G14459A in a percentage close to homoplasmy and in low heteroplasmy in her mother. The rest of the maternally related family members analyzed were negative., Conclusion: The G14459A mutation, although not very frequently associated to Leigh syndrome, should be analyzed in patients that do not present the most common point mutations.

Aim: To describe the scientific contributions and biography of Giuseppe Attardi (1923-2008), in particular his work on the human mitochondrial genetic system of crucial importance for the discovery and understanding of the mechanisms that produce the mitochondrial diseases., Development: Giuseppe Attardi was an Italian-born medical doctor that worked with outstanding researchers as James Watson, Francois Jacob, and Renato Dulbecco, all Nobel Prizes of Medicine until 1963 that was promoted to Professor of the California Institute of Technology in Pasadena (USA). In 1967 discovered the human mitochondrial RNA, a little later the mitochondrial ribosomes and proteins encoded in the genome, in 1981 showed the genetic and transcription map of the mitochondrial DNA, and in 1983 described the proteins codified in this genome, all of them components of the oxidative phosphorylation system, metabolic pathway that leads to the synthesis of ATP. Later, he developed a technique, widely used nowadays, to study the mechanism by which the mutations in the mitochondrial DNA altered the cellular function and originated the mitochondrial diseases. In 1999, demonstrated the role of the mitocondrial DNA, and the mutations produced along the life, in aging.

Introduction: Mitochondrial encephalopathy, lactic acidosis and cerebrovascular accident syndrome (MELAS) is, from the clinical point of view, one of the best studied mitochondrial multisystemic disorders. This disease has mainly been associated to the mitochondrial desoxyribonucleic acid (mtDNA) mutation A3243G located in the tRNALeu(UUR) gene. Although a relation between European haplogroups and the presence of the 3243 mutation has not been described, nothing is known about the presence of this mutation in native American haplogroups., Case Report: A 12 year-old female Mexican patient diagnosed with MELAS is reported. Besides neurological, biochemical and cytological examination, we also analyzed the particular mtDNA mutations related to MELAS and the whole genome was sequenced to determine the mitochondrial haplogroup. The A3243G mutation was detected in the patient and maternal relatives (mother and siblings, all of them asymptomatic). The genotype corresponds to the native American haplogroup B2 and contains two private non-synonymous polymorfisms., Conclusion: All the members of the family studied present different percentage of the A3243G mutation, being the patient who presented the highest value. The mtDNA genotype corresponds to the native American haplogroup B2 and the private polymorphisms do not confer any phenotypic modification in MELAS syndrome.

Aim: The diseases of the oxidative phosphorylation system consist of a group of disorders originated by a deficient synthesis of adenosine triphosphate (ATP). These diseases are increasingly being diagnosed among patients with multisystemic disorders. Mitochondrial deoxyribonucleic acid (mtDNA) mutations are usually maternally inherited, but they also can be sporadic or secondary to nuclear mutations, that are inherited in a Mendelian mode, or due to environmental hazards. In this review we will update, from a genetic point of view, the knowledge on human mitochondrial diseases, remarking the difficulties to study these pathologies., Development: To mirror these difficulties, we will use selected examples of mutations in the mitochondrial genome, and review recent advances on mitochondrial pathology due to mutations in the nuclear genes codifying for mitochondrial proteins that participate in a good performance of the oxidative phosphorylation system., Conclusions: Sequencing of the complete human mtDNA should be part of the basic profile in the study of mitochondrial diseases. Due to the increasing number of nuclear genes involved in the oxidative phosphorylation system performance, their analysis should be based on solid biochemical clues.

Introduction: A large number of diseases present as bilateral striatal lesion syndrome (BSLS). Clinical manifestations, course and prognosis of these diseases are extremely variable. On the basis of their evolutive course, they can be separated into two major groups: acute, which include toxic, infectious or parainfectious causes, and subacute or chronic, in which inborn errors of metabolism, especially mitochondrial disorders, are the main causes., Case Report: We report a detailed clinical follow-up of a 18 years old Caucasian male who, at the age of four, presented with BSLS. A respiratory chain defect was suspected on the basis of slowly progressive dystonia and cognitive impairment, changes in serial MRI studies, and the finding of 'trabecular fibers' as well as a 50% decrease of the complex I activity in striated-skeletal muscle specimen. Blood, urine and CSF markers classically associated with respiratory chain diseases were normal. Molecular studies identified a new pathogenetic mutation (T14487C) in the mitochondrial ND6 gene of the respiratory chain complex I., Conclusion: Mitochondrial metabolism disorders should be ruled out in patients presenting with a subacute or chronic form of BSLS even in the absence of other common mitochondrial disease markers.

Introduction: The syndrome of chronic progressive external ophthalmoplegia (CPEO) is a mitochondrial disease characterized by ptosis and ophthalmoplegia has that has been associated to the presence of large deletion, single or multiple, in the mitochondrial DNA of skeletal muscle., Case Report: We report a familiar case of chronic progressive external ophthalmoplegia of maternal inheritance that began at birth, and developed with slow progression but with no multisystemic involvement. Non of the affected individuals had ragged-red fibers in skeletal muscle. Genetic analysis of mitochondrial DNA revealed the presence of a single deletion of 4,977 bp that encompasses the nucleotide positions 8,482 to 13,460, flanked by a direct repeat sequence., Conclusions: The amount of deleted mitochondrial DNA (15%) in this patient's muscle suggests, even if the percentage of the mutation is low, that this deletion is the molecular cause of the phenotypic presentation of this patient. This is one of the few cases described in the literature of CPEO maternally inherited.

Introduction: The syndrome of chronic progressive external ophthalmoplegia (CPEO) has been associated to the presence of large deletion, single or multiple, in the mitochondrial DNA of skeletal muscle., Case Report: We report a sporadic case of chronic progressive external ophthalmoplegia that began at age 19 years and was associated with ragged red fibers in skeletal muscle. Genetic analysis of mitochondrial DNA revealed the presence of a single deletion of 4237 bp that encompasses the nucleotide positions 9486 to 13722, a location that has not been described before, and flanked by a direct repeat sequence. The deletion is flanked by a direct repeat., Conclusions: The amount of deleted mitochondrial DNA (55%) in this patient's muscle suggests that this deletion is the molecular cause of the phenotypic presentation of this patient.

Introduction: Several degenerative neurological diseases are caused by mutations in the mitochondrial gene coding for subunit 6 of the ATPase. Thus, NARP (neurogenic weakness, ataxia, and retinitis pigmentosa) and Leigh syndromes are associated to a T8993G mutation when the percentage of mutant mitochondrial DNA is low (60 90%) or high (>90%), respectively. Leigh syndrome is also caused by a second mutation in the same position T8993C., Case Report: The patient, a boy that died at 6 months, had generalized hypotonia, psychomotor delay, hepatomegaly, choreic movements and hyporreflexia. MRI showed hypodensities in the basal ganglia and brain stem as well as hyperlactacidemia. Molecular genetic analysis of the mitochondrial DNA showed that the patient had the T8993G mutation in a percentage higher than 95%. No mutated DNA was detected in blood of the proband s mother, maternal aunt and grandmother., Conclusions: The point mutation T8993G may occur de novo, at high levels, causing neurodegenerative diseases.

Introduction: Human diseases caused by disorders of the mitochondrial metabolism have been described more than 30 years ago. Some of these are associated to defects in the oxidative phosphorylation system (OXPHOS system), the final pathway of the mitochondrial energetic metabolism, that leads to the synthesis of ATP., Development: Part of the polypeptide subunits involved in the OXPHOS system are codified by the mitochondrial DNA (mtDNA). In the last 12 years, mutations (point mutations or deletions) in the mtDNA have been described and associated to well defined clinical syndromes caused by defects in the OXPHOS system. The clinical features of these diseases are very heterogeneous affecting in most cases to a great variety of organs and tissues., Conclusions: The correct diagnosis of these mitochondrial disorders require precise clinical, morphological, biochemical, and genetic data. The rapid advances in genetic analysis allow the rapid detection of mutations, even before the obtention of other type of analysis.

Introduction: The existence of neuropathy has been described in mitochondrial disorders such as MELAS, MERRF, Leigh's syndrome, the Kearns-Saye syndrome, myoneurogastro-intestinal encephalopathy and progressive external ophthalmoplegia and constitutes a basic component of the NARP (neuropathy, ataxia and retinosis pigmentosa). However, the general prevalence of the neuropathy and its characteristics within the mitochondrial encephalopathies is not well understood., Objectives: To characterize the neuropathy and try to establish a genotype-phenotype correlation., Patients and Methods: Within study guidelines, we made a retrospective study of 27 patients, diagnosed as having mitochondrial disease, who had had neurophysiological studies (EMG-ENG). In those in whom neuropathy had been found we analysed the clinical, neurophysiological and genetic characteristics., Results: Neuropathy was present in 37% of the patients who had an average age of 13 years, ranging from 1 to 25 years. Syndromic diagnoses were: 7 encephalomyopathies, one MELAS, one MERRF and one NARP. Four of the patients were classified genetically. In all but two of the patients the neuropathy was asymptomatic. The biochemical alterations seen were: deficit of Complex 1 in 3 patients, of complex III in 3 patients, of complex IV in 2 and of pyruvate dehydrogenase in one patient. The type of neuropathy found was varied, with predominance of axonal-type motor neuropathy but no correlation with either biochemical defects or genetic diagnosis., Conclusions: Neuropathy is a common finding in mitochondrial disorders and probably is under-diagnosed. The axonal form predominates. We have not been able to establish correlations between phenotypes and genotypes.

Introduction: The mitochondria, subcellular organelles which possess their own DNA (mtDNA), produce most of the energy, in the form of ATP, which is necessary for life. This mtDNA may have diverse molecular defects which have been associated with a great variety of clinical syndromes. Deletions in mtDNA are one of the common mutations in patients with mitochondrial myopathies, which in the great majority present with the common symptom of progressive external ophthalmoplegia. In this study we report our findings in eight Cuban families with suspected mitochondrial disease., Objectives: To characterize these patients from the molecular point of view, which would allow a preliminary understanding of the behavior of these deletions in Cuban patients., Patients and Methods: We studied nine patients from eight Cuban families in whom mitochondrial encephalomyopathy was suspected. We analyzed the presence of ragged red fibres, the enzymatic activity of the mitochondrial respiratory chain and detection of mtDNA mutations. We used the technique of restriction length polymorphism analysis for detection of deletions., Results: Histochemical studies showed the presence of COX negative ragged red fibres in seven of the patients studied. The enzymatic activity of the mitochondrial respiratory chain was normal in all the patients. We detected four patients with single deletions of mtDNA, and one with multiple deletions and of the patients had the A3243G mutation., Conclusions: With the methods used we were able to determine the presence of a mitochondrial disorder in seven of the eight families studied and deletions of mtDNA were detected as the cause of the illness in five. The disorder was always associated with progressive external ophthalmoplegia and COX negative ragged red fibres.

Introduction: Deletions of mitochondrial DNA (mtDNA) are a known cause of various mitochondrial cytopathies, which are sporadic and usually not due to maternal transmission. The multiple deletions are usually transmitted on a Mendelian pattern, and are frequently of autosomal dominant character. Leukodystrophy may be part of the picture, or even the form of presentation, of some mitochondrial cytopathies. Thus, in a case of leukoencephaly of unknown origin, mitochondrial cytopathy should be considered in the differential diagnosis., Clinical Case: We present the case of a boy with no previous clinical abnormalities who, at the age of 13, suddenly fell to the floor with an encephalopathy which required aggressive treatment, needing mechanical ventilation and prolonged sedation. Following partial recovery spastic-dystonic quadriplegia remained. Neuroimaging showed advanced leukodystrophy with small hemorrhages in the white matter, which later disappeared. After rejecting other aetiologies, mitochondrial cytopathies in muscle were studied. A partial defect of the I and IV complexes of the respiratory chain and two deletions of mtDNA were shown., Conclusions: This case is another example of the variable clinical presentation of mitochondrial cytopathies and yet another argument for their inclusion in the diagnosis of leukodystrophy of unknown origin.

The mitochondria are subcellular organelles devoted to energy production in form of ATP that contain their own genetic system. Mitochondrial DNA codify a small, but extremely important, number of polypeptides of the respiratory chain. The other mitochondrial proteins are encoded in the nucleus. Therefore, mitochondrial biogenesis require the coordinated expression of nuclear and mitochondrial genetic systems. The gene arrangement in mitochondrial DNA is extremely compact with the tRNA genes interspersed with the rRNA and protein-coding genes. This organization has its precise counterpart in the mode of expression and distinctive structural features of the RNAs. Both mitochondrial DNA strands are transcribed as a whole in the form of three polycistronic molecules that are later cut by specific enzymes that recognize the 5' and 3' end of the tRNA sequences, to produced the mature rRNA, mRNA and tRNA. The mitochondrial coded mRNAs are translated into proteins by a mitochondrial specific protein-synthesizing machinery. The genetics of the mitochondrial DNA differs from that of the nuclear DNA in several features. In particular, the mitochondrial genome is inherited from the mother that transmit their mitochondrial DNA to all her offsprings. Another characteristic of this genome is its tendency to mutate more frequently than the nuclear DNA. This provides a powerful tool for studying the evolution of man.