Ophthalmoplegia

Enteric Myopathies. The familial types include the dominant type 1 [150], the recessive type 2 with ophthalmoplegia [151] and the recessive type 3 [116]. The sporadic types include muscular dystrophies [152] including myotonic dystrophy [153] and Duchenne s dystrophy. Dysmotility has been associated with all these diseases. 

Anuras S, Mitros FA, Nowak TV, Ionasescu W, Gurll NJ, Christensen J, Green JB A familial visceral myopathy with external ophthalmoplegia and autosomal recessive transmission. Gastroenterology 1983,84 346-353. 

Thiamine deficiency results in early decreases in activity of the mitochondrial enzyme a-ketoglutarate dehydrogenase in brain. Wernicke s encephalopathy, also known as the Wernicke-Korsakoff syndrome is a neuropsychiatric disorder characterized by ophthalmoplegia, ataxia and memory loss. Wernicke s encephalopathy is encountered in chronic alcoholism, in patients with HIV-AIDS and in other disorders associated with grossly impaired nutritional status. The condition results from thiamine deficiency. 

PEO progressive external ophthalmoplegia RER rough endoplasmic reticulum... 

The spectrum of cognitive deficits associated with chronic alcohol use extends to the extreme of Wernicke s encephalopathy and Korsakoff s psychosis. Wernicke s encephalopathy is an acute neurologic syndrome caused by thiamine deficiency. Symptoms include mental confusion, ophthalmoplegia, and ataxia. Many of these symptoms reverse with administration of thiamine however about 50% of patients are left with some degree of ataxia. Left untreated, Wernicke s encephalopathy can progress to stupor, coma, and death. Approximately 80% to 90% of alcoholics treated for Wernicke s encephalopathy are left with Korsakoff s psychosis, a syndrome of impaired learning and recent memory produced by lesions of the medial dorsal nuclei of the thalamus. 

CNS toxicity includes headache, mental confusion, internal ophthalmoplegia, peripheral neuritis, depression, optical neuritis. 

Axonal degeneration, ophthalmoplegia (however, vitamin E deficiency does not occur clinically). 

Beriberi (characterized by nerve involvement - peripheral neuritis), Wernicke s encephalopathy (characterized by ophthalmoplegia, polyneuritis and mental disorientation). 

The clinical manifestations are axonal degeneration, gait disturbances, ophthalmoplegia, hyporeflexia and necrotizing myopathy. 

Central and/or peripheral nervous system involvement is one of the most frequent features, often resulting in the neonatal period in drowsiness, poor sucking, severe hypotonia, abnormal movements, seizures, respiratory distress, and fatal keto-acidotic coma with lactic acidosis [3]. To these severe conditions echo late-onset diseases now frequently attributed to or associated with mitochondrial OXPHOS defects, such as Alzheimer s or Parkinsons disease [10]. Major neurological symptoms, in variable combinations, involve trunk hypotonia, cranial nerve and brainstem involvement (with abnormal eye movements, ophthalmoplegia, recurrent apneas), cerebellar ataxia, myoclonia, seizures, pyramidal syndrome, peripheral neuropathy, poliodystrophy, and leukodystrophy infections [27,28]. A diffuse impairment of the cerebral white matter (leukodystrophy) mostly results in motor disturbance with mental retardation and low incidence of seizures. 

PEO [25] A myopathy with progressive muscle weakness and external ophthalmoplegia. Ataxia, episodic ke-toacidotic coma, and early death have been reported associated with single or multiple DNA deletions. Mutations in the gene encoding the muscle isoform of the adenylate carrier (ANTI) have been reported to cause PEO, presumably due to abnormal nucleotide availability for mtDNA synthesis. 

The eye can be involved in generalized adverse reactions to systemically administered glucocorticoids. For example, conjunctivitis can occur as part of an allergic reaction and infections of the eye can be masked as a result of antiinflammatory and analgesic effects. Ophthalmoplegia can occur as one of the consequences of glucocorticoid myopathy (SEDA-16, 450). Two complications that require special discussion are cataract and glaucoma. 

Negevesky GJ, Kolsky MP, Laureno R, Yau TH. Reversible atorvastatin-associated external ophthalmoplegia, anti-acet-ylcholine receptor antibodies, and ataxia. Arch Ophthalmol 2000 118(3) 427—8. 

Monnier, N., Ferreiro, A., Marty, I., Labarre-Vila, A., Mezin, P., and Lunardi, J. (2003). A Homozygous Splicing Mutation Causing a Depletion of Skeletal Muscle RYR1 is Associated with Multi-Minicore Disease Congenital Myopathy with Ophthalmoplegia. Hum Mol Genet 12(10) 1171—8. 

Ophthalmoplegia Optic neuropathy Pigmentary retinal degeneration Cataract... 

MELAS, Mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes CPEO, chronic progressive external ophthalmoplegia LHON, Leber hereditary optic neuropathy NARP, neurogenic muscle weakness, ataxia, and retinitis pigmentosa NIDDM, non-insulin-dependent diabetes mellitus TER, termination. 

B5. Bohlega, S., Tanji, K., Santorelli, F. M., Hirano, M., al-Jishi, A., and DiMauro, S., Multiple mitochondrial DNA deletions associated with autosomal recessive ophthalmoplegia and severe mitochondrial myopathy. Neurology 46, 1329-1334 (1996). 

M21. Miiller-Hocker, J., Stiinkel, S., Pongratz, D., and Hiibner, G., Focal deficiency of cytochrome-c-oxidase and of mitochondrial ATPase combined with loosely coupled oxidative phosphorylation in the skeletal muscle of a patient with progressive external ophthalmoplegia An enzyme histochemical, immunocytochemical and fine structure study. J. Neurol. Sci. 69, 27-36 (1985). 

P7. Piccolo, G., Banfi, P., Azan, G., Rizzuto, R., Bisson, R., Sandona, D., and Bellomo, G., Biological markers of oxidative stress in mitochondrial myopathies with progressive external ophthalmoplegia. J. Neurol. Sci. 105, 57-60 (1991). 

S10. Shoffner, J. M., Lott, M. T., Voljavec, A. S., Soueidan, S. A., Costigan, D. A., and Wallace, D. C., Spontaneous Kearns-Sayre/chronic external ophthalmoplegia plus syndrome associated with a mitochondrial DNA deletion A slip-replication model and metabolic therapy Proc. Natl. Acad. 

V3. van Goethem, G., Dermaut, B., Lofgren, A., Martin, J. J., and van Broeckhoven, C., Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions. Nat. Genet. 28, 211-212 (2001). 

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