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Query: UMLS:C0029089 (ophthalmoplegia)
 3,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report 2 brothers with progressive ataxia, seizures, myoclonus, supranuclear ophthalmoplegia, progressive visual loss and embolic strokes. The epilepsy and myoclonus came on many years after the onset of the ataxia. In the more severely affected brother the myoclonus was often unilateral and focal but ultimately involved both sides of the body. His sibling had only unilateral myoclonus after a contralateral middle cerebral artery stroke. When focal, persistent and unilateral, the myoclonus in both brothers was clinically similar to epilepsia partialis continua except that muscles of the trunk and proximal limbs were the most affected. It was exacerbated by movement of the affected part but was otherwise not stimulus sensitive. The more severely affected brother had a pigmentary retinopathy and a cardiac fibromyxoid valvulopathy. In his sibling, visual loss was not fully investigated and the heart was not examined at autopsy though he had a longstanding heart murmur. Neuropathological studies showed pancerebellar cortical atrophy, cell loss in the inferior olivary nuclei and old right middle cerebral artery infarctions in both brothers. Biochemical assays for known metabolic diseases were negative. We suggest that this syndrome represents a unique autosomal recessive form of progressive myoclonus epilepsy of unclear aetiology. It is distinguished from other familial myoclonus epilepsies by the presence of early onset cerebellar ataxia, supranuclear ophthalmoplegia, pigmentary retinopathy and possibly cardiac valvulopathy with subsequent cerebral emboli.
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PMID:Myoclonus epilepsy in two brothers. Clinical features and neuropathology of a unique syndrome. 308 70

A comparative histochemical analysis of the prevalence and cytochrome oxidase staining characteristics of ragged-red fibres in limb skeletal muscles was performed in 19 patients spanning four distinct mitochondrial syndromes: chronic progressive external ophthalmoplegia; myoclonus epilepsy with ragged-red fibres; mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes; and pure limb myopathy. The percentage occurrence of non-ragged red but cytochrome oxidase negative fibres was additionally noted. Ragged-red fibres and cytochrome oxidase-negative fibres were generally more prevalent in the chronic progressive external ophthalmoplegia syndrome than in myoclonus epilepsy ragged-red fibres syndrome or mitochondrial myopathy encephalopathy lactic acidosis and stroke-like episodes syndrome. Isolated cytochrome oxidase-negative fibres were a common finding in each phenotypic syndrome except pure limb myopathy and could involve any of the major fibre types non-specifically. Ragged-red fibres were devoid of cytochrome oxidase activity in chronic progressive external ophthalmoplegia, but commonly displayed activity in the other three syndromes providing a clue to syndromal differentiation on a histochemical basis.
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PMID:Contrasting histochemical features of various mitochondrial syndromes. 762 56

Defects of the mitochondrial respiratory chain are associated with a great variety of clinical disorders. Whilst recognition of these conditions is increasing, the need for sophisticated biochemical and molecular studies has tended to limit both their investigation and diagnosis to a few specialist centres. Using a group of 51 patients with histochemically, biochemically and/or genetically defined respiratory chain defects, we have examined both the clinical heterogeneity of these disorders and how they may be investigated most effectively in non-specialist centres. We evaluated the use of the following routinely available clinical investigations--fasting intermediary metabolites (lactate, pyruvate, ketone bodies, etc.) in blood and cerebrospinal fluid, serum creatine kinase estimation, EMG, EEG, CT, MRI and histological/histochemical muscle biopsy analysis. Our studies show that, in addition to well-recognized syndromes (e.g. chronic progressive external ophthalmoplegia, mitochondrial encephalopathy lactic acidosis and stroke like episodes, and myoclonus epilepsy with ragged red-fibres, a significant number of patients present with non-specific encephalopathic disorders. Furthermore, even within those categories of respiratory chain disease which have been genetically defined, a wide variation of presenting symptoms and signs were found. Where there was initial doubt concerning the diagnosis, the following clinical features were helpful in suggesting respiratory chain disease: ophthalmoplegia; a maternal pattern of inheritance; the presence of myopathy or deafness in association with encephalopathy. Of the clinical investigations we assessed, elevated lactate in blood or cerebrospinal fluid and low density lesions in the basal ganglia were helpful in identifying patients with respiratory chain dysfunction. Histochemical analysis of muscle was, however, the single most useful investigation being diagnostic in patients with chronic progressive external ophthalmoplegia, Kearns-Sayre syndrome and myopathy, and of significant importance in patients presenting primarily with central nervous system disease. The results of our study are used to discuss the most appropriate approach to diagnosis of this group of disorders.
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PMID:Presentation and clinical investigation of mitochondrial respiratory chain disease. A study of 51 patients. 773 77

We have investigated nine children with infantile onset of mitochondrial myopathy and two adults with myoclonus epilepsy and ragged-red fibers (MERRF) and chronic progressive external ophthalmoplegia (CPEO), respectively. These patients lacked any of the previously known pathogenic tRNA mutations. Southern blot analysis of muscle mtDNA revealed no deletions. The tRNA genes of muscle mtDNA were sequenced. Restriction enzyme analysis of PCR fragments was performed to verify the presence of the mutations identified by automatic sequencing. Several tRNA mutations were found, but they were all homoplasmic. Furthermore, the mutations were either present in controls or did not change nucleotides conserved between species. This strongly suggests that none of the tRNA mutations identified in the 11 patients with mitochondrial encephalomyopathy was pathogenic. It can thus be concluded that mitochondrial tRNA mutations and mtDNA deletions probably are an infrequent cause of mitochondrial disorders in infants. Patients with MERRF and CPEO may lack both pathogenic point mutations of tRNA genes and deletions of mtDNA.
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PMID:Automatic sequencing of mitochondrial tRNA genes in patients with mitochondrial encephalomyopathy. 815 39

We identified two patients with pathogenic single nucleotide changes in two different mitochondrial tRNA genes: the first mutation in the tRNA(Asn) gene, and the ninth known mutation in the tRNA(Leu(UUR)) gene. The mutation in tRNA(Asn) was associated with isolated ophthalmoplegia, whereas the mutation in tRNA(Leu(UUR)) caused a neurological syndrome resembling MERRF (myoclonus epilepsy and ragged-red fibers) plus optic neuropathy, retinopathy, and diabetes. Both mutations were heteroplasmic, with higher percentages of mutant mtDNA in affected tissues, and undetectable levels in maternal relatives. Analysis of single muscle fibers indicated that morphological and biochemical alterations appeared only when the proportions of mutant mtDNA exceeded 90% of the total cellular mtDNA pool. The high incidence of mutations in the tRNA(Leu(UUR)) gene suggests that this region is an "etiologic hot spot" in mitochondrial disease.
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PMID:Two novel pathogenic mitochondrial DNA mutations affecting organelle number and protein synthesis. Is the tRNA(Leu(UUR)) gene an etiologic hot spot? 825 46

Recent discoveries in mitochondrial clinical genetics have revealed that a broad spectrum of clinical phenotypes are associated with mutations in mitochondrial DNA. Diseases caused by mutations in mitochondrial DNA are by nature quantitative. Myoclonic epilepsy and ragged-red fiber disease are caused by a mutation in the transfer RNA gene lysine. Although everyone in a maternal lineage will harbor the same mutation, the nature and severity of the symptoms vary markedly among individuals. This variability correlates with the inherited percentage of mutations in the individual's mitochondrial DNA and the individual's age. Age-related expression of mitochondrial disease has also been demonstrated for mitochondrial DNA deletions. Although deletions that retain both origins of replication result in late-onset disease because of the progressive enrichment of the deleted mitochondrial DNA, a 10.4-kb deletion that lacks the light-strand replication origin and maintains a stable mutant percentage in both tissues and cultured cells has been discovered. This deletion is associated with adult-onset diabetes and deafness, but not with ophthalmoplegia, ptosis, or mitochondrial myopathy. Biochemically, it causes a generalized defect in mitochondrial protein synthesis and oxidative phosphorylation. The age-related decline in oxidative phosphorylation could reflect the accumulation of somatic mitochondrial DNA mutations. Inhibition of oxidative phosphorylation stimulates this accumulation. The general paradigm for mitochondrial DNA diseases may be that inherited mutations inhibit the electron transport chain. This damages the mitochondrial DNA, further reducing oxidative phosphorylation. Ultimately, oxidative phosphorylation drops below the expression threshold of cells and tissues, and clinical symptoms appear.
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PMID:Mitochondrial DNA mutations in epilepsy and neurological disease. 829 23

We found that patients with mitochondrial encephalomyopathies excreted urinary phosphatidylethanolamine, cardiolipin, and phosphatidylserine most likely derived from mitochondria and sulfatide which is specific to myelin or the kidney. It is of interest that four patients with myoclonus epilepsy with ragged-red fibers and one patient with chronic progressive external ophthalmoplegia all showed qualitatively similar abnormal excretion of such urinary lipids. It is conceivable that the urinary acidic phospholipids reflect abnormalities in the mitochondrial phospholipids, which are very important for mitochondrial enzymatic activities.
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PMID:Abnormal excretion of urinary phospholipids and sulfatide in patients with mitochondrial encephalomyopathies. 833 41

We report a 64-year-old man presenting with multiple symmetric lipomatosis (MSL) and mitochondrial encephalomyoneuropathy. The diagnosis of a mitochondrial cytopathy was based on the typical clinical symptoms and signs, including chronic progressive external ophthalmoplegia, hearing impairment, cerebellar ataxia, proximal myopathy, and polyneuropathy, and on molecular genetic and histological examinations. As a unique finding, the A-->G(8344) myoclonus epilepsy and ragged-red fibers point mutation was found in peripheral nerve, muscle, and adipose tissue. Muscle biopsy revealed multiple ragged-red fibers and other morphological signs of a mitochondrial myopathy. Sural nerve biopsy demonstrated a mixed axonal and demyelinating neuropathy with extensive loss of myelinated fibers and conspicuous onion bulb formations, as well as structural mitochondrial abnormalities on electron microscopy. These findings clearly demonstrate mitochondrial dysfunction in muscle, adipose tissue, and for the first time also in nervous tissue of an MSL patient, and strongly support the concept of mitochondrial cytopathy as one of the possible causes of multiple symmetric lipomatosis.
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PMID:Mitochondrial dysfunction with myoclonus epilepsy and ragged-red fibers point mutation in nerve, muscle, and adipose tissue of a patient with multiple symmetric lipomatosis. 917 55

We report a short-term double-blind, crossover study of CoQ10 in 8 patients with mitochondrial encephalomyopathies. Four patients had myoclonus epilepsy with ragged-red fibers syndrome, 3 had mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes syndrome, and 1 had chronic progressive external ophthalmoplegia with myopathy. A trend of effectiveness of CoQ10 in several parameters was noted. Fatigability of daily activities was alleviated. The endurance to muscle exercise was augmented. Global muscle strength scored by Medical Research Council scale was increased. The extent of elevation in serum lactate and pyruvate levels after exercise was decreased. However, only the global MRC index score had a statistical significance (p < 0.05). There were no side effects during therapy. The serum CoQ10 levels were significantly lower in patients than in normal controls before CoQ10 treatment and increased significantly after treatment.
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PMID:Coenzyme Q10 treatment in mitochondrial encephalomyopathies. Short-term double-blind, crossover study. 920 60

We investigated endocrine function in patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), myoclonus epilepsy associated with ragged-red fibers (MERRF), and chronic progressive external ophthalmoplegia (CPEO). Hypothalamic-pituitary function was impaired in all three patients with MELAS or MERRF, but none of four with CPEO. A MELAS patient with dwarfism and impaired adolescent development had decreased growth hormone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). A MERRF patient had emaciation and low adrenocorticotropin. A patient with mitochondrial encephalomyopathy transitional between MELAS and MERRF showed delayed, blunted LH and FSH response to LH-releasing hormone stimulation. We concluded that patients with mitochondrial encephalomyopathies, especially MELAS or MERRF, are likely to have hypothalamic-pituitary dysfunction.
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PMID:Dysfunction of the hypothalamic-pituitary system in mitochondrial encephalomyopathies. 970 89


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