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

Lead exposure is an ancient malady. Its history serves as a useful paradigm through which to understand many other pollutants that our technological society has inserted into the human environment and may guide preventive steps for other agents. Lead poisoning was first recognized in workers exposed to high doses. The discovery of childhood toxicity occurred a century ago in Australia, when children with striking symptoms of paralysis, ophthalmoplegia, or meningitis were found to be highly lead exposed. Encephalopathy generally occurs at blood lead levels of 80 micrograms/dL or more, but unequivocal brain damage has been demonstrated at doses well below this level. At lower doses, the neurocognitive effects of lead are expressed as diminished psychometric intelligence, attention deficits, conduct problems, alterations in the electroencephalogram, school failure, and increased referral rates for special needs. Careful epidemiologic studies, which have controlled for the important confounders, have set the effect level at 10-15 micrograms/dL. Elegant animal studies in which confounding is not an issue have confirmed these findings. Although blood lead levels in the population have dropped over time for a number of reasons, there are some 3-4 million American children with blood lead levels of more than 15 micrograms/dL. Biochemical and functional changes have been demonstrated in the heme biosynthetic pathway and in the renal, cardiovascular, endocrine, immune, and nervous systems. The threshold for effect depends on the sensitivity of the methods used. A no-effect level has not been found. Further, this is not a disease of the poor alone. But the poor are exposed to much more lead than are the more economically favored. Deficiencies in body calcium, zinc, iron, and protein stores are associated with increased uptake. Optimizing nutrition enhances the resistance to lead. All children should be screened for lead at regular intervals, especially those with anemia, growth failure, and developmental or behavioral problems. Treatment protocols are well worked out, but chelation is only part of the therapy. Controlling the environment, strengthening the family's supports, enhancing nutrition, and offering remedial education are essential to a successful therapeutic outcome. Lead control has involved a continuing struggle between vested economic interests and regulatory agencies. In one area, the control of airbone lead, science, and public health have prevailed. In the past decade, the amount of alkyl lead consumed in gasoline additives has been reduced by 99%. Body lead burdens have dropped in close correspondence.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The persistent threat of lead: medical and sociological issues. 306 40

This study describes mitochondrial cytochemistry with reference to cytochrome c oxidase and NADH oxidase activities as well as calcium localization at subcellular level in a variety of human mitochondrial disorders. The enzyme activities, calcium homeostasis, and myofibrillary architecture were retained in the lipid storage myopathies with carnitine and carnitine palmityl transferase deficiency. The loss of enzyme reaction, excessive Ca++ deposit, and myonecrosis were the features of the group comprised of a variety of disorders with mitochondrial pathology (Kearns-Sayre's syndrome, chronic progressive ophthalmoplegia, polymyositis, neurogenic atrophy, and fascioscapulo humeral dystrophy). Based on these and our previous experimental study (Shah et al., 1985), we suggest that the human mitochondrial disorders may be grouped into two types: one in which the morphologically altered mitochondria retain the enzyme activities and Ca++ homeostasis and the other in which the altered mitochondria associated with muscle necrosis represent the loss/reduction of the enzyme activities as well as Ca++ homeostasis.
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PMID:Variability of mitochondrial cytochemistry in human neuromuscular diseases. 339 68

Two patients, one with ataxia, internuclear ophthalmoplegia, muscle weakness, atrophy, fasciculations, and bilateral Babinski's signs, the other with dysarthria, dysphagia, muscle weakness, atrophy, fasciculations, and hyperreflexia, had elevated serum calcium and parathyroid hormone levels, establishing the diagnosis of primary hyperparathyroidism (HPT). Removal of a parathyroid adenoma in one patient and three hyperplastic parathyroid glands in the other resulted in remission of the hyperparathyroidism but left both patients with residual neurological damage. Postmortem examination of the second patient showed typical features of amyotrophic lateral sclerosis. The findings in these patients show that hyperparathyroidism may be associated with signs of severe central nervous system disease and that patients with unexplained neurological signs or symptoms should be checked for hyperparathyroidism.
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PMID:Severe neurological disease associated with hyperparathyroidism. 673 92

Nine cases of mitochondrial myopathy are presented and the literature is reviewed. The clinical picture ranges from virtually pure ophthalmoplegia, through 'ophthalmoplegia plus' to predominantly central nervous system disturbance. Morphological mitochondrial abnormalities are likely to reflect generalised metabolic abnormalities of diverse aetiology, but producing common pathophysiological consequences. The association of mitochondrial myopathy with CNS disorders, which may ante-date muscle weakness, is emphasised. The myopathies constitute a clinical continuum within which the following syndromes may be delineated: (1) Kearns-Sayre syndrome (2) Luft's disease (3) a variant of Ramsay Hunt syndrome (4) relapsing febrile neurological deficits with headache and seizures. These may be specific diseases or artificially separated manifestations of some common metabolic disorder(s). There is a similarity between the CNS pathology, and also some clinical features, of Leigh's disease and the findings in certain of the mitochondrial myopathies. The review suggests that the following should be regarded as associations of mitochondrial myopathy and progressive external ophthalmoplegia (a) diabetes mellitus (b) cataracts, in which calcium deposits may, like basal ganglia calcification, be due to abnormal calcium metabolism. Diplopia, although unusual, does occur in progressive external ophthalmoplegia with mitochondrial myopathy.
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PMID:The mitochondrial myopathies: 9 case reports and a literature review. 734 99

We report a 17-year-old girl with short stature, external ophthalmoplegia, atypical retinal pigmentary degeneration, sensorineural hearing loss, and cardiac conduction defect (Kearns-Sayre syndrome). A large-scale deletion (6741 base pairs) in mitochondrial DNA was found in her muscle specimen. She also had insulin-dependent diabetes mellitus (IDDM). On admission, her plasma glucose level was elevated at 31.0mmol/l with mild ketoacidosis, and haemoglobinA1c elevated at 16.5%. After improvement of diabetic ketoacidosis, she was placed on insulin 24-30 units/day despite her small body weight of 25 kg. There was reduced excretion of urinary C-peptide at 3.97 nmol/day. In addition, she had idiopathic hypoparathyroidism with a serum calcium level of 2.15 mmol/l, phosphate 1.7 mmol/l, and intact PTH below 10 ng/l. Human leucocyte associated antigen typing showed A24, A26; B54, B61; CW1, CW3; DR8, DR14; DQ1 and DQ3, suggesting that the presence of HLA-A24 and CW3 antigen contributed to the association of IDDM and hypoparathyroidism, similar to Japanese patients with polyglandular autoimmune syndrome, complicated by hypoparathyroidism and IDDM. We suggest that a genetic linkage, as well as mitochondrial dysfunction, may be responsible for the association of the two disease states. This is an extremely rare case of Kearns-Sayre syndrome, presenting in association with IDDM and idiopathic hypoparathyroidism.
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PMID:Hypoparathyroidism and insulin-dependent diabetes mellitus in a patient with Kearns-Sayre syndrome harbouring a mitochondrial DNA deletion. 897 63

Mitochondrial dysfunction is implicated in bipolar disorder based on the following lines of evidence: 1) Abnormal brain energy metabolism measured by 31P-magnetic resonance spectroscopy, that is, decreased intracellular pH, decreased phosphocreatine (PCr), and enhanced response of PCr to photic stimulation. 2) Possible role of maternal inheritance in the transmission of bipolar disorder. 3) Increased levels of the 4977-bp deletion in mitochondrial DNA (mtDNA) in autopsied brains. 4) Comorbidity of affective disorders in certain types of mitochondrial disorders, such as autosomal inherited chronic progressive external ophthalmoplegia and mitochondrial diabetes mellitus with the 3243 mutation. Based on these findings, we searched for mtDNA mutations/ polymorphisms associated with bipolar disorder and found that 5178C and 10398A polymorphisms in mtDNA were risk factors for bipolar disorder. The 5178C genotype was associated with lower brain intracellular pH. mtDNA variations may play a part in the pathophysiology of bipolar disorder through alteration of intracellular calcium signaling systems. The mitochondrial dysfunction hypothesis, which comprehensively accounts for the pathophysiology of bipolar disorder, is proposed.
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PMID:Mitochondrial dysfunction in bipolar disorder. 1125 81

Although swallowing difficulties have been described in patients with Kearns-Sayre syndrome (KSS), the spectrum of manometric characteristics of dysphagia is not yet well known. Moreover, it is conceivable that a combination of various degrees of swallowing difficulties with different patterns in manometric studies exist, each playing a major role in the prognosis, natural history, and quality of life of KSS patients. An 18-year-old girl diagnosed at the age of 5 years with KSS (muscle biopsy) was admitted to our department with an upper respiratory tract infection and dysphagia. Clinical examination revealed growth retardation, external ophthalmoplegia, pigmentary retinopathy, impaired hearing, and ataxia. An electrocardiogram revealed cardiac conduction defects (long Q-T), and brain magnetic resonance imaging showed abnormalities in the cerebellar hemispheres. A manometric and motility study for dysphagia was conducted and the pharynx and upper esophageal sphincter (UES) resting pressures were similar to control group values, but the swallowing peak contraction pressure of the pharynx and the closing pressure of the UES were very low and could not promote effective peristaltic waves. Relaxation and coordination of the UES were not affected although pharyngeal and upper esophagus peristaltic waves proved to be very low and, consequently, were practically ineffective. The patient was started on treatment comprising a diet rich in potassium, magnesium, and calcium, and oral administration of vitamin D and co-enzyme Q10 100 mg daily; she was discharged 6 days later with apparent clinical improvement.
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PMID:Manometric study in Kearns-Sayre syndrome. 1142 10

In mammalian cells, mitochondria provide energy from aerobic metabolism. They play an important regulatory role in apoptosis, produce and detoxify free radicals, and serve as a cellular calcium buffer. Neurodegenerative disorders involving mitochondria can be divided into those caused by oxidative phosphorylation (OXPHOS) abnormalities either due to mitochondrial DNA (mtDNA) abnormalities, e.g., chronic external ophthalmoplegia, or due to nuclear mutations of OXPHOS proteins, e.g., complex I and II associated with Leigh syndrome. There are diseases caused by nuclear genes encoding non-OXPHOS mitochondrial proteins, such as frataxin in Friedreich ataxia (which is likely to play an important role in mitochondrial-cytosolic iron cycling), paraplegin (possibly a mitochondrial ATP-dependent zinc metalloprotease of the AAA-ATPases in hereditary spastic paraparesis), and possibly Wilson disease protein (an abnormal copper transporting ATP-dependent P-type ATPase associated with Wilson disease). Huntingon disease is an example of diseases with OXPHOS defects associated with mutations of nuclear genes encoding non-mitochondrial proteins such as huntingtin. There are also disorders with evidence of mitochondrial involvement that cannot as yet be assigned. These include Parkinson disease (where a complex I defect is described and free radicals are generated from dopamine metabolism), amyotrophic lateral sclerosis, and Alzheimer disease, where there is evidence to suggest mitochondrial involvement perhaps secondary to other abnormalities.
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PMID:Mitochondria and degenerative disorders. 1157 22

Kearns-Sayre syndrome (KSS) is a multisystem mitochondrial disorder characterized by the invariant triad: onset before 20, progressive external ophthalmoplegia and pigmentary retinal degeneration, plus at least one of the following: complete (or not) heart block, cereberal dysfunction and CSF protein above 100 mg/dl. Autopsies from patients with KSS revealed widespread tissue distribution mtDNA deletions. These deletions result in significantly lower activities of the enzymes of the respiratory chain. The same deletion of mitochondrial DNA present in skeletal muscle is found in myocardial tissue. An 18-year-old girl diagnosed with the KSS was admitted to our hospital because of an upper respiratory tract infection and dysphagia. ECG showed cardiac conduction defects. The patient had no history of syncope. At her surface ECG there was a complete RBBB (QRS duration approximately 130 ms), a clockwise rotation with an axis of approximately 90 degrees and a slight QT prolongation (420 ms). Echocardiography showed prolapse with thickening and degeneration of both mitral valve leaflets but without mitral regurgitation. The patient was started on a diet rich in potassium and pharmaceutical therapy with magnesium oxide (240 mg of elemental Mg p.o. per day), 1 g of calcium carbonate t.i.d., vitamin D (calcitriol 0.25 microg p.o. per day) and coenzyme Q(10) 100 mg daily and discharged 6 days later with slightly improved biochemical profile but apparent clinical improvement. Urgent pacemaker implantation was decided but unfortunately the patient died due to acute cardiac arrest 10 days later.
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PMID:Alarming atrioventricular block and mitral valve prolapse in the Kearns-Sayre syndrome. 1200 93

The ryanodine receptor (RYR1) is an essential component of the calcium homeostasis of the skeletal muscle in mammals. Inactivation of the RYR1 gene in mice is lethal at birth. In humans only missense and in-frame mutations in the RYR1 gene have been associated so far with various muscle disorders including malignant hyperthermia, central core disease and the moderate form of multi-minicore disease (MmD). We identified a cryptic splicing mutation in the RYR1 gene that resulted in a 90% decrease of the normal RYR1 transcript in skeletal muscle. The 14646+2.99 kb A-->G mutation was associated with the classical form of MmD with ophthalmoplegia, whose genetic basis was previously unknown. The mutation present at a homozygous level was responsible for a massive depletion of the RYR1 protein in skeletal muscle. The mutation was not expressed in lymphoblastoid cells, pointing toward a tissue specific splicing mechanism. This first report of an out-of-frame mutation that affects the amount of RYR1 raised the question of the amount of RYR1 needed for skeletal muscle function in humans.
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PMID:A homozygous splicing mutation causing a depletion of skeletal muscle RYR1 is associated with multi-minicore disease congenital myopathy with ophthalmoplegia. 1271 81


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