Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029089 (ophthalmoplegia)
 3,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 51-year-old woman with no history of any familial neurological diseases initially presented with numbness in her extremities, slowing of movements, comprehension deficit, memory disturbance, dyscalculia, muscle rigidity, hyperreflexia, Parkinsonian gait, increasing disorientation, left-right disturbance, finger agnosia, alexia, acalculia, apraxia, aspontaneity, euphoria, gait disturbance, aphasia, echolalia, and in the terminal stage, mutism, contracture of lower extremities and cachexia. She died of bronchopneumonia at the age of 55. The brain showed widespread cerebral lesions, consisting of nerve cell loss and neurofibrillary tangles in the frontal, parietal and occipital cortex, demyelination and gliosis in the frontal, parietal and occipital subcortical white matter in addition to the typical pathological findings of progressive supranuclear palsy (PSP): severe neuronal loss with gliosis and neurofibrillary tangles (NFTs) in the subthalamic nucleus, globus pallidus and substantia nigra. In conclusion, we present a case of PSP with unusual clinical features (extrapyramidal signs, frontal and parietal lobe syndromes without ophthalmoplegia) and neuropathologically widespread cerebral lesions in addition to the typical pathological findings of PSP. The differential diagnosis of PSP and Alzheimer's disease and other degenerative disorders is discussed.
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PMID:Progressive supranuclear palsy with widespread cerebral lesions. 147 14

Few parkinsonian patients present with 'pure akinesia' or with severe akinesia accompanied by only mild rigidity, tremor and other manifestations such as ophthalmoplegia. Pathological examinations of such cases have rarely been conducted and have revealed findings compatible with progressive supranuclear palsy (PSP), pallido-nigro-luysian atrophy (PNLA) or Parkinson's disease. We report a parkinsonian patient whose main clinical feature was akinesia. A postmortem study of this patient showed findings corresponding to PNLA and PSP. Histochemical properties of the pallidal pigment granules were equivalent to those of Hallervorden-Spatz disease (HSD) and striatonigral degeneration. In addition to iron-positive pigment granules, spheroids, severe neuronal loss and gliosis in the globus pallidus and substantia nigra, formation of Alzheimer's neurofibrillary tangle (NFT) in the brainstem shares characteristics with PSP, adult onset HSD and PNLA. We suggest that the underlying pathology of 'pure' akinesia is most often situated in the globus pallidus substantia nigra and subthalamus (Luys), and that PSP, PNLA and adult onset HSD may constitute a spectrum of one disease.
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PMID:Pallido-nigro-luysian atrophy, progressive supranuclear palsy and adult onset Hallervorden-Spatz disease: a case of akinesia as a predominant feature of parkinsonism. 170 2

We present a review on recent neuroimaging techniques, like x-ray computed tomography (XCT), magnetic resonance imaging (MRI), positron emission tomography (PET) and single photon emission tomography (SPECT) in dementia and related diseases. Significant new findings have been obtained using techniques reflecting proton density, regional brain perfusion and brain metabolism. In dementia of the Alzheimer type, for example, temporoparietal and sometimes also frontal reductions in cerebral blood flow and metabolism are characteristic. The infarctions found in multi-infarct dementia are especially well visualized on T2-weighted MRI images. Pick's disease is characterized by brain atrophy and decrease of radiotracer activity in the frontal lobes. In huntington's chorea the metabolic rate on PET scan in the area of the caudate nuclei may be reduced even before signs and symptoms become apparent. Furthermore, neuroimaging provides us with fairly typical finding in Creutzfeld-Jakob's disease, alcoholic dementia, Wilson's disease, hydrocephalus, Parkinson's disease, progressive supranuclear ophthalmoplegia, Fahr's disease, and the olivopontocerebellar ataxias. Neuroimaging techniques, however, have always to be interpreted in conjunction with clinical findings, thus disclosing their full range of information.
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PMID:[Diagnostic differentiation of dementia diseases by modern imaging procedures]. 227 95

We describe a case of an adult-onset progressive dystonia with external ophthalmoplegia, occurring in a black man without a family history of neurologic disorders. Neuropathologic examination demonstrated neuronal loss and gliosis in the anterior horn and Clarke's column in the spinal cord, nuclei of cranial nerves III, VI, X, and XII, vestibular complex, lateral cuneate nucleus, lower pontine tegmentum, red nucleus, substantia nigra, and dentate nucleus. The cerebral cortex, corpus striatum, basis pontis, inferior olives, and cerebellum were spared. The clinical and pathologic findings closely resemble autosomal-dominant motor system degeneration or "Azorean disease," without, however, demonstrable familial transmission. In addition to the absence of a family history, unique features of the case include the presence of Alzheimer type II glial cells in the red nucleus and an unexplained persistent elevated concentration of serum amylase.
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PMID:Sporadic case resembling autosomal-dominant motor system degeneration (Azorean disease complex). 382 87

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

The objective of this study is to better define the pathological characteristics of pathologically proven progressive supranuclear palsy (PSP) presenting with the corticobasal syndrome (CBS). PSP is characterized by early falls, vertical supranuclear ophthalmoplegia, and axial rigidity, whereas asymmetric limb features, including rigidity, bradykinesia, apraxia, alien limb phenomena, and cortical sensory loss are characteristic of CBS. We investigated clinicopathological characteristics of 5 cases of PSP that presented with CBS (CBS-PSP). Comprehensive pathological analysis was undertaken to determine the presence of concomitant pathological processes as well as quantitative tau burden in cortical regions of CBS-PSP, compared with 8 typical PSP cases (Typ-PSP). The clinical features in the CBS-PSP cases included asymmetrical features, apraxia, alien limb phenomena, and progressive aphasia. All cases had Parkinsonism, and vertical supranuclear ophthalmoplegia was noted in all but 1 case of CBS-PSP. Secondary neuropathological diagnoses included argyrophilic grain disease (AGD) in 1 of the 8 cases of Typ-PSP, whereas Alzheimer's disease (AD), Lewy body disease, AGD, and vascular disease was found in 3 cases of CBS-PSP. Image analysis of cortical tau burden performed in 8 Typ-PSP and 3 CBS-PSP cases revealed a significant increased tau burden in mid-frontal and inferior-parietal cortices in the CBS-PSP cases. This study demonstrates that when PSP presents as CBS, it is most likely due to either a concurrent cortical pathology from a secondary process such as AD or from the primary pathology of PSP extending into cortical areas that are primarily and commonly affected in CBD.
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PMID:Increased tau burden in the cortices of progressive supranuclear palsy presenting with corticobasal syndrome. 1583 57

We showed that humanin (HN), an endogenous peptide against Alzheimer disease-related insults, was expressed in muscles of patients with chronic progressive external ophthalmoplegia (CPEO), a major mitochondrial disease. Because HN was recently found to block proapoptotic Bax function and exert its versatile cytoprotective effects in association with an increase in ATP levels, HN expression may thus reflect a physiological response against degenerative changes in the muscles of patients with CPEO. We found HN expression in all four patients examined, each of whom had different mitochondrial DNA mutations including two different single DNA deletions, multiple deletions, and no major mutations detected. We also found that HN expression was not linked to focal cytochrome c deficiency, strongly associated with the subtype of CPEO with single deletions. These results suggest that HN expression is more closely related to degenerative changes in all types of CPEO. Notably, HN was also expressed in non-degenerative muscle fibers of patients with CPEO or Leigh syndrome, who had the 8993T>G mutation in the mitochondrial ATPase 6 gene known to be associated with impaired ATP synthesis. Collectively, our findings suggest that HN may be specifically expressed in response to defects in energy production in muscles with mitochondrial abnormalities.
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PMID:Humanin expression in skeletal muscles of patients with chronic progressive external ophthalmoplegia. 1663 4

Defects of mitochondrial metabolism cause a wide range of human diseases that include examples from all medical subspecialties. This review updates the topic of mitochondrial diseases by reviewing the most important recent advances in this area. The factors influencing inheritance, maintenance and replication of mtDNA are reviewed and the genotype-phenotype of mtDNA disorders has been expanded, with new insights into epidemiology, pathogenesis and its role in ageing. Recently identified nuclear gene mutations of mitochondrial proteins include mutations of frataxin causing Friedreich's ataxia, PINK1, DJ1 causing Parkinson's disease and POLG causing infantile mtDNA depletion syndrome, ophthalmoplegia, parkinsonism, male subfertility and, in a transgenic mouse model, premature senescence. Mitochondrial defects in neurodegenerative diseases include Parkinson's, Alzheimer's and Huntington's disease. Improved understanding of mtDNA inheritance and mutation penetrance patterns, and novel techniques for mtDNA modification offer significant prospects for more accurate genetic counselling and effective future therapies.
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PMID:Mitochondrial disease. 1681 81

We present here the clinicopathological characteristics of two autopsy-confirmed cases comorbid of progressive supranuclear palsy (PSP) and Alzheimer's disease (AD). Histopathologically, the amount and distribution of neurofibrillary tangles (NFTs) in the basal ganglia and brainstem fulfilled the pathological criteria of PSP proposed by the National Institute of Neurological Disorders and Stroke--The Society for PSP (NINDS-SPSP). The Braak stages of senile plaques and NFTs were stage C and stage V in Case 1, and stage C and stage IV in Case 2. These neuropathological findings confirmed that the two patients had combined PSP with AD. Our patients presented clinically with executive dysfunction prior to memory disturbance as an early symptom. Not only neurological symptoms such as gait disturbance, supranuclear ophthalmoplegia and pseudobulbar palsy, but emotional and personality changes and delirium were prominent. Therefore, symptoms of subcortical dementia of PSP were more predominant than AD-related symptoms in the present two patients. Comorbid PSP and AD further complicates the clinical picture and makes clinical diagnosis even more difficult.
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PMID:Progressive supranuclear palsy combined with Alzheimer's disease: a clinicopathological study of two autopsy cases. 1899 14

Variations in the mitochondrial helicase Twinkle (PEO1) gene are usually associated with autosomal dominant chronic progressive external ophthalmoplegia (PEO). We describe five patients from two unrelated Alsatian families with the new R374W variation in the Twinkle linker region who progressively developed an autosomal dominant multisystem disorder with PEO, hearing loss, myopathy, dysphagia, dysphonia, sensory neuropathy, and late-onset dementia resembling Alzheimer's disease. These observations demonstrate that Twinkle variations in the linker domain alter cerebral function and further implicate disrupted mitochondrial DNA integrity in the pathogenesis of dementia.
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PMID:A novel variation in the Twinkle linker region causing late-onset dementia. 1951 67


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