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)

At the end of the XIXth century, the first cases of primary progressive ophthalmoplegia reported were related to a primary degeneration of the oculomotor nuclei; and this concept was accepted until there were considered of purely muscular origin in the 1950's. From this time and during twenty years these cases were reported as ocular myopathies. However the coexistence of neurological abnormalities and above all, the presence of mitochondrial abnormalities in the muscles, the brain and the tissues rich in energy, gave ground to the concept of mitochondrial encephalomyopathies. Then the nature of the dysfunctioning was assessed through biochemical studies, mainly the enzyme deficits of the respiratory chain mitochondria. But correlations between clinical and biochemical data were still difficult as these cases corresponded either to muscular damage (myalgia, exercise intolerance), either to various neurological alterations (epilepsy, cerebellar syndrome) or to multisystemic manifestations. Molecular biology technics introduced the notion of mitochondrial inheritance which contributed to underline the identity of certain varieties, mainly the Kearns and Sayre Syndrome. The increasing number of cases with mitochondrial abnormalities leads to the inverse approach: in central or peripheral damage of the nervous system or in very variable muscular alterations, the investigation of a mitochondrial dysfunctioning is justified and shows the way to possible therapies. This evolution of concept is remarkable in the history of medicine. An abnormality which, at first, was considered as an esthetic alteration, became the subject of the study which, through the advances of the clinical data, of the pathological anatomy, biochemistry and genetics, explained the mechanism of several alterations of the muscles and of the nervous system.
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PMID:[The history of mitochondrial encephalomyopathies]. 193 79

The parkinsonian syndrome rests on the clinical tripod: akinesia, rigidity, tremor. Akinesia is the key symptom, broadly defined as a difficulty in initiating and performing movements in proportion to their complexity (sophisticated, simultaneous movements) and their duration (repetitive movements). The most frequent cause of the syndrome is Parkinson's disease. Although this diagnosis needs to be confirmed in pathological terms by the loss of neurons and the presence of Lewy's bodies in the substantia nigra, some clinical data enable it to be envisaged with a minimum of errors; these are pure parkinsonian triad, good response to dopatherapy and asymmetrical symptoms. The other causes of parkinsonian syndrome are usually related to the administration of neuroleptic drugs and to degenerative diseases with lesions that are more diffuse than those of Parkinson's disease. In Steele-Richardson-Olzewski disease a parkinsonian syndrome is associated with supranuclear ophthalmoplegia. Multiple systematized atrophy presents under three different clinical aspects: a parkinsonian syndrome without tremor and resistant to L-dopa, suggesting atrophy of the strionigral tract; a parkinsonian syndrome associated with a cerebellar syndrome, suggesting olivo-cerebellar-pontine atrophy, and Shy-Drager disease which includes primary dysautonomy and other neurological syndromes.
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PMID:[Parkinson's disease and parkinsonian syndromes]. 272 71

The authors give a very complete description of the Kearns and Sayre syndrome : external ophthalmoplegia, pigmentary retinitis, cardiac conduction disorders, cerebellar syndrome, hypacusis, reduced height, raised CSF protein levels, mitochondrial anomalies in muscle, skin, and conjunctivae, and low density zones on scanning. They emphasize the not-infrequent association of endocrine anomalies : hypoparathyroidism, which may be the first manifestation of the disease, and diabetes. The etiology of this syndrome, which occurs sporadically and starts in infancy, is still unknown.
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PMID:[Kearns and Sayre syndrome with hypoparathyroidism and diabetes (author's transl)]. 625 52

The clinical features of 11 families containing 73 individuals with dominantly inherited cerebellar ataxia of late onset are described. Many of the patients had physical signs in addition to cerebellar ataxia, which included dementia, supranuclear ophthalmoplegia, extrapyramidal dysfunction, optic atrophy, pigmentary retinal degeneration, myoclonus and deafness. These associated features were generally very variable within members of the same family. Intrafamilial correlation of age of onset and an analysis of clustering of clinical features within families using X2 tests suggested that there was little evidence of genetic heterogeneity in the eight kindreds where ophthalmoplegia, optic atrophy, dementia, or extrapyramidal signs were found in affected individuals. One of these families contained descendants of the 'Drew family of Walworth' described by Ferguson and Critchley in 1929. The three other families contained patients with clinically distinct syndromes which were: cerebellar ataxia with pigmentary retinal degeneration; a later onset (over 60 years) 'pure' cerebellar syndrome; and an ataxia disorder associated with myoclonus and deafness. A simple classification of the autosomal dominant cerebellar ataxias is proposed and discussed in relation to previous attempts to classify these disorders on clinical and pathological grounds.
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PMID:The clinical features and classification of the late onset autosomal dominant cerebellar ataxias. A study of 11 families, including descendants of the 'the Drew family of Walworth'. 706 68

We report a family affected by autosomal dominant ataxia, in which numerous members also showed microcytosis. Genetic analysis demonstrated a CAG expansion in the SCA1 locus in five members, while all subjects with microcytosis revealed a C-T substitution at codon 39 of the beta-globin gene. A pure cerebellar syndrome with prominent gait ataxia characterized the first stages of the neurological disease. The fully developed disease included additional clinical findings such as dysarthria and dysphagia, and instrumental signs of axonal involvement of the peripheral nerves. Ophthalmoplegia was not observed. The coexistence of hereditary spinocerebellar degeneration and erythropathies or hemoglobinopathies has been previously described. We discuss the possible linkages between these two pathologies.
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PMID:Clinical and genetic study of a family with spinocerebellar ataxia type 1 (SCA1) and beta-thalassemia. 1093 28

Spinocerebellar ataxias (SCAs) are a clinically heterogeneous group of disorders. Current molecular classification corresponds to the order of gene description (SCA1-SCA 25). The prevalence of SCAs is estimated to be 1-4/100,000. Patients exhibit usually a slowly progressive cerebellar syndrome with various combinations of oculomotor disorders, dysarthria, dysmetria/kinetic tremor, and/or ataxic gait. They can present also with pigmentary retinopathy, extrapyramidal movement disorders (parkinsonism, dyskinesias, dystonia, chorea), pyramidal signs, cortical symptoms (seizures, cognitive impairment/behavioral symptoms), peripheral neuropathy. SCAs are also genetically heterogeneous and the clinical diagnosis of subtypes of SCAs is complicated by the salient overlap of the phenotypes between genetic subtypes. The following clinical features have some specific values for predicting a gene defect: slowing of saccades in SCA2, ophthalmoplegia in SCA1, SCA2 and SCA3, pigmentary retinopathy in SCA7, spasticity in SCA3, dyskinesias associated with a mutation in the fibroblast growth factor 14 (FGF 14) gene, cognitive impairment/behavioral symptoms in SCA17 and DRPLA, seizures in SCA10, SCA17 and DRPLA, peripheral neuropathy in SCA1, SCA2, SCA3, SCA4, SCA8, SCA18 and SCA25. Neurophysiological findings are compatible with a dying-back axonopathy and/or a neuronopathy. Three patterns of atrophy can be identified on brain MRI: a pure cerebellar atrophy, a pattern of olivopontocerebellar atrophy, and a pattern of global brain atrophy. A remarkable observation is the presence of dentate nuclei calcifications in SCA20, resulting in a low signal on brain MRI sequences. Several identified mutations correspond to expansions of repeated trinucleotides (CAG repeats in SCA1, SCA2, SCA3, SCA6, SCA7, SCA17 and DRPLA, CTG repeats in SCA8). A pentanucleotide repeat expansion (ATTCT) is associated with SCA10. Missense mutations have also been found recently. Anticipation is a main feature of SCAs, due to instability of expanded alleles. Anticipation may be particularly prominent in SCA7. It is estimated that extensive genetic testing leads to the identification of the causative gene in about 60-75 % of cases. Our knowledge of the molecular mechanisms of SCAs is rapidly growing, and the development of relevant animal models of SCAs is bringing hope for effective therapies in human.
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PMID:The wide spectrum of spinocerebellar ataxias (SCAs). 1589 52

The brainstem is an uncommon site of a brain abscess. Such lesions, which were invariably fatal, changed with the arrival of computed tomography and magnetic resonance imaging (MRI). These not only helped in the diagnosis but also in treatment management. A 51-year old patient was diagnosed of widespread pontomesencephalic abscess. He was admitted with a clinical picture of dizziness, headache and involvement of multiple cranial nerves with near complete ophthalmoplegia and cerebellar syndrome in the side of the lesion and contralateral hemiplegia. Microbiologic investigations were negative and the medical management decided was broad spectrum antibiotic and periodic MRI controls. The length of the lesion decreased (from 4 cm in diameter to 0.5 cm) with progressive improvement of the neurological deficits. Treatment of large brainstem abscesses includes primary antibiotic therapy combined with stereotaxic drainage, but in individual cases empirical medical therapy can be effective. Sequential MRI examinations are very important for monitoring treatment efficacy.
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PMID:[Widespread brainstem abscess resolved with medical therapy]. 1732 39

Paraneoplastic retinopathy including cancer-associated retinopathy (CAR) and melanoma-associated retinopathy (MAR), and paraneoplastic optic neuropathy (PON) are visual disorders associated with systemic cancer. Patients with CAR typically present with progressive loss of vision and photopsia, which are related to dysfunction of both cones and rods in photoreceptors. The triad of photosensitivity, ring scotoma, and a reduced caliber of the retinal arteriole along with undetectable signals in electroretinogram (ERG) are specific manifestations of CAR. CAR is associated most commonly with small-cell lung cancer (SCLC) and occasionally with gynecologic tumors, and it is usually caused by autoantibodies against recovering, which is a calcium-binding photoreceptor protein that participates in the transduction of light. MAR is characterized by shimmering, flickering, or pulsating photopsias, and usually occurs in the patients with a cutaneous melanoma. MAR differs from CAR in terms of visual acuity and color vision and is associated with a characteristic pattern detected in ERG. Autoantibodies against the bipolar cells of the retina have been identified in patients with MAR. Patients with PON frequently present with progressive visual loss and optic disc edema, or with other paneoplastic neurologic syndromes related to SCLC, such as paraneoplastic encephalomyelitis or retinitis, ophthalmoplegia, and subacute cerebellar syndrome. Autoantibodies against collapsin-responsive mediator protein-5 (CRMP-5, also called anti-CV2) are considered to be as the causative factor. Treatments with corticosteroids, plasma exchange, and intravenous immune globulin as well as treatment of the tumor itself, occasionally improves these paraneoplastic visual syndromes. However, the prognosis depends on their underlying malignancy.
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PMID:[Paraneoplastic retinopathy and optic neuropathy]. 2042 Jan 77

The cerebellum is a brain region which is particularly susceptible to intoxication. Clinical presentation is heterogeneous. It is often considered that elderly patients and patients presenting pre-existing structural lesions of the posterior fossa are particularly at risk of developing a toxic-induced cerebellar syndrome (TOICS). However, TOICS may occur at any age, including in utero. Indeed, the cerebellum is highly vulnerable during neurodevelopment. Amongst cerebellotoxic agents, ethanol is the most commonly implicated. The vermis is a privileged target. Ethanol exerts toxic effects upon neurons, glia (especially astrocytes and oligodendrocytes), and myelin sheaths. Prenatal alcohol exposure causes teratogenic effects on the developing cerebellum, impeding neuronal migration and differentiation. In adults, cerebellar ataxia is a major feature of both acute and chronic ethanol intoxication. Wernicke encephalopathy is a medical emergency characterized by a triad of ophthalmoplegia, ataxia, and impaired mental status. It requires the immediate administration of high doses of thiamine by the intravenous route. The following drugs may induce a permanent cerebellar syndrome: phenytoin, lithium salts, antineoplastics, and heroin. In addition to ethanol and drugs, environmental agents are also a source of TOICS. In particular, the cerebellum is susceptible to metal intoxication. The recently described deposits of gadolinium in cerebellar nuclei in patients who had received multiple intravenous administrations are a matter of concern on a worldwide scale but we still lack the demonstration of clinically relevant effects upon motor, oculomotor, or cognitive function. Because cerebellar symptoms may be subtle or immersed in a complex encephalopathy with combined involvement of the peripheral nervous system, the diagnosis of TOICS is often overlooked. The life-threatening risk of edema of the posterior fossa with compression of the brainstem should be kept in mind, including in cases of posterior reversible encephalopathy syndrome, and requires posterior fossa decompression when acute hydrocephalus occurs.
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PMID:Toxic-induced cerebellar syndrome: from the fetal period to the elderly. 2989 Oct 70

The autosomal dominant spinocerebellar ataxias (SCAs) consist of a highly heterogeneous group of rare movement disorders characterized by progressive cerebellar ataxia variably associated with ophthalmoplegia, pyramidal and extrapyramidal signs, dementia, pigmentary retinopathy, seizures, lower motor neuron signs, or peripheral neuropathy. Over 41 different SCA subtypes have been described evidencing the high clinical and genetic heterogeneity. We previously reported a novel spinocerebellar ataxia type subtype, SCA37, linked to an 11-Mb genomic region on 1p32, in a large Spanish ataxia pedigree characterized by ataxia and a pure cerebellar syndrome distinctively presenting with early-altered vertical eye movements. Here we demonstrate the segregation of an unstable intronic ATTTC pentanucleotide repeat mutation within the 1p32 5' non-coding regulatory region of the gene encoding the reelin adaptor protein DAB1, implicated in neuronal migration, as the causative genetic defect of the disease in four Spanish SCA37 families. We describe the clinical-genetic correlation and the first SCA37 neuropathological findings caused by dysregulation of cerebellar DAB1 expression. Post-mortem neuropathology of two patients with SCA37 revealed severe loss of Purkinje cells with abundant astrogliosis, empty baskets, occasional axonal spheroids, and hypertrophic fibres by phosphorylated neurofilament immunostaining in the cerebellar cortex. The remaining cerebellar Purkinje neurons showed loss of calbindin immunoreactivity, aberrant dendrite arborization, nuclear pathology including lobulation, irregularity, and hyperchromatism, and multiple ubiquitinated perisomatic granules immunostained for DAB1. A subpopulation of Purkinje cells was found ectopically mispositioned within the cerebellar cortex. No significant neuropathological alterations were identified in other brain regions in agreement with a pure cerebellar syndrome. Importantly, we found that the ATTTC repeat mutation dysregulated DAB1 expression and induced an RNA switch resulting in the upregulation of reelin-DAB1 and PI3K/AKT signalling in the SCA37 cerebellum. This study reveals the unstable ATTTC repeat mutation within the DAB1 gene as the underlying genetic cause and provides evidence of reelin-DAB1 signalling dysregulation in the spinocerebellar ataxia type 37.
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PMID:Clinical, genetic and neuropathological characterization of spinocerebellar ataxia type 37. 2993 98


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