Revisiting mitochondrial ocular myopathies: a study from the Italian Network.

Ocular myopathy, typically manifesting as progressive external ophthalmoplegia (PEO), is among the most common mitochondrial phenotypes. The purpose of this study is to better define the clinical phenotypes associated with ocular myopathy. This is a retrospective study on a large cohort from the database of the "Nation-wide Italian Collaborative Network of Mitochondrial Diseases". We distinguished patients with ocular myopathy as part of a multisystem mitochondrial encephalomyopathy (PEO-encephalomyopathy), and then PEO with isolated ocular myopathy from PEO-plus when PEO was associated with additional features of multisystemic involvement. Ocular myopathy was the most common feature in our cohort of mitochondrial patients. Among the 722 patients with a definite genetic diagnosis, ocular myopathy was observed in 399 subjects (55.3%) and was positively associated with mtDNA single deletions and POLG mutations. Ocular myopathy as manifestation of a multisystem mitochondrial encephalomyopathy (PEO-encephalomyopathy, n = 131) was linked to the m.3243A>G mutation, whereas the other "PEO" patients (n = 268) were associated with mtDNA single deletion and Twinkle mutations. Increased lactate was associated with central neurological involvement. We then defined, among the PEO group, as "pure PEO" the patients with isolated ocular myopathy and "PEO-plus" those with ocular myopathy and other features of neuromuscular and multisystem involvement, excluding central nervous system. The male proportion was significantly lower in pure PEO than PEO-plus. This study reinforces the need for research on the role of gender in mitochondrial diseases. The phenotype definitions here revisited may contribute to a more homogeneous patient categorization, useful in future studies and clinical trials.

Robotic gait training improves motor skills and quality of life in hereditary spastic paraplegia.

BACKGROUND: Gait impairment, balance problems and falls have a negative impact on independence in ADL and quality of life of patients affected by Hereditary Spastic Paraplegia (HSP). Since no pharmacological options are available, treatments rely mostly on rehabilitation therapy, although almost no data on this topic exist. Given the demonstrated effectiveness of robotics in improving gait and balance in various neurological diseases, aim of this study is to test the effectiveness of a robotic-aided program of gait training on balance, walking ability and quality of life in adult subjects affected by uncomplicated HSP. METHODS: Thirteen patients affected by uncomplicated HSP were subjected to a six-week robotic-aided gait training protocol. Participants underwent a battery of 3 walking test, 1 balance test and 2 quality of life questionnaires. RESULTS: At the end of the treatment a significant improvement of balance, walking ability and quality of life was observed in almost all the tests. The improvements were maintained over a two-month follow-up period. CONCLUSIONS: Our study indicates that a robotic gait training is long term effective in improving balance and walking ability with a positive impact on quality of life in patients affected by uncomplicated form of HSP. As currently there is no specific treatment to prevent or reverse HSP progression, our contribution would be significant for the development of exercise recommendations in this rare disease.

Amyotrophic Lateral Sclerosis: A Genetic Point of View.

In the last twenty years the rapid advances in neurogenetic have revolutionized not only the molecular, pathological, inheritance but also the clinical concept of ALS. Here we review the current genetic breakthrough in familial and sporadic ALS, considering how this knowledge has allowed widening of the scenario on the possible pathogenic disease mechanisms and better understanding of the relationship between the genetic, pathological and clinical subtypes.

Common Genetic Conditions of Ischemic Stroke to Keep in Mind.

Stroke is a complex disease resulting from the interplay of genetics and environment. In some instances (mainly in young adults) stroke is the direct result of a monogenic disease. Among the monogenic causes of stroke, the diseases which are most frequently encountered in the adult general neurological practice are CADASIL, Fabry and mitochondrial diseases. Brain MRI and clinical features may frequently lead to a correct molecular diagnosis. Here we review the single-gene causes of ischemic stroke, with special regard to the associated features which may help in the diagnostic approach.

Targeting mitochondrial dysfunction and neurodegeneration by means of coenzyme Q10 and its analogues.

Coenzyme Q10 is a small electron carrier of the respiratory chain with antioxidant properties, widely used for the treatment of mitochondrial disorders. Mitochondrial diseases are neuromuscular disorders caused by impairment of the respiratory chain and increased generation of reactive oxygen species. Coenzyme Q10 supplementation is fundamental in patients with primary coenzyme Q10 deficiency. Furthermore, coenzyme Q10 and its analogues, idebenone and mitoquinone (or MitoQ), have been also used in the treatment of other neurogenetic/neurodegenerative disorders. In Friedreich ataxia idebenone may reduce cardiac hypertrophy and, at higher doses, also improve neurological function. These compounds may also play a potential role in other conditions which have been linked to mitochondrial dysfunction, such as Parkinson disease, Huntington disease, amyotrophic lateral sclerosis and Alzheimer disease. This review introduces mitochondrial disorders and Friedreich ataxia as two paradigms of the tight links existing between oxidative stress, respiratory chain dysfunction and neurodegeneration, and focuses on current and emerging therapeutic uses of coenzyme Q10 and idebenone in neurology.