Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026838 (spasticity)
 6,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a 2-year-old boy with Leigh disease, spasticity, dysarthria, and optic atrophy gradually developed. Computed tomography and magnetic resonance imaging disclosed progressive, symmetric basal ganglia lesions. In muscle tissue, a defect of pyruvate dehydrogenase complex was found. Magnetic resonance volume selective proton spectroscopy (MRVS) of the basal ganglia demonstrated an abnormal lactate peak. A ketonemic diet coincided with clinical stabilization and arrest of progressive brain lesions. Lactate could no longer be demonstrated by MRVS. It reappeared with a new brain lesion coinciding with discontinuation of the diet. MRVS, therefore, appears to be a sensitive tool to evaluate pathologic lactate production in metabolic brain disease with disturbed energy metabolism and allows noninvasive therapy monitoring.
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PMID:Assessment and therapy monitoring of Leigh disease by MRI and proton spectroscopy. 155 78

A one-year-old boy suffering from intermittent lactic acidosis, muscular hypotonia, horizontal gaze paralysis and spasticity in both legs had low activity of the pyruvate dehydrogenase complex associated with low amounts of immunoreactive E 1 alpha and E 1 beta. Leigh syndrome was diagnosed on the basis of the clinical and biochemical abnormalities and the typical lesions observed on MRI of the brain. Treatment with a ketogenic diet was associated with clinical and biochemical amelioration. A striking improvement of the cerebral lesions was observed by neuro-imaging.
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PMID:Leigh syndrome associated with a deficiency of the pyruvate dehydrogenase complex: results of treatment with a ketogenic diet. 164 Oct 82

A 19-year-old man presented with an apparently non-familial neurological disorder that had progressed from the age of 6 years. Dystonia of the trunk and limbs with extrapyramidal rigidity, dysarthria, a pyramidal syndrome with spasticity of the lower limbs, bilateral optic atrophy, and nystagmiform ocular movements were present. CT scan demonstrated symmetrical putaminal lesions. The different aetiologies of bilateral striatal lesions are considered, the final diagnosis being a juvenile form of Leigh's disease.
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PMID:[Extrapyramidal rigidity with dystonia, optic atrophy and bilateral putaminal lesions in an adolescent. Juvenile form of Leigh's disease (author's transl)]. 710 Jul 40

Fourteen patients (10 boys, 4 girls) aged from 4 months to 14 years old were diagnosed with mitochondrial disease based on the clinical manifestations together with abnormal muscle mitochondrial morphologies. Their clinical diagnoses included Leigh syndrome, three; Menkes' syndrome, three; Kearns-Sayre syndrome, two; myoclonic epilepsy with ragged fibres, one; and infant-onset progressive myoclonic epilepsy, one; fatal infantile mitochondrial myopathy, one; fatty acid oxidation defect, two; and myopathy with cardiopathy, one. Organs involved other than muscles included central nervous system, ten; heart, six; eye, two; liver, two; and kidney, two. Clinical manifestations varied to include hypotonia, seizures, myoclonus, mental retardation, nystagmus, ataxia, ptosis, ophthalmoplegia, retinal degeneration, muscle atrophy, spasticity etc. Nine had an abnormal rise in lactate after glucose loading. Ragged-red fibres were found in four patients. Abnormal mitochondrial morphology included abnormal accumulation, abnormal cristae pattern of tubular, concentric, or parallel form, some contained osmiophilic inclusion bodies. One patient of Leigh syndrome had had brain necropsy which showed intramyelin splitting of myelinated axons.
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PMID:Clinical manifestation of mitochondrial diseases in children. 821 54

Management of severe spasticity in children is often a difficult problem. Orally administered medications generally offer limited benefits. This study examines the value of intrathecally administered baclofen in the treatment of 19 children with severe spasticity of cerebral origin: eight of whom sustained brain injury associated with trauma, near drowning, or cardiac arrest; 10 with cerebral palsy (spastic quadriplegia); and one child with Leigh's disease. At the time of entry into the study, patients ranged from 4 to 19 years of age, and all were completely dependent on caretakers for activities of daily living. Children who responded positively to a trial dose of intrathecal baclofen underwent insertion of a drug delivery system for continuous infusion. This was followed by a double-blind trial of baclofen or placebo and follow-up review at 3 and 6 months, and yearly thereafter. Seven children did not undergo pump implantation because of excess sedation or poor response. The 12 remaining children have been followed for a period of 1 to 5 years. Favorable responses were present in all 12 children as determined by the Ashworth Scale, with the greatest benefit being reduction of lower limb tone. Except in the case of one child who had reduction in lower limb tone that resulted in difficulty with transfers, the caretakers all reported significant benefits from intrathecal baclofen, with improvement in muscle tone, behavior, sitting, and general ease of care being most commonly noted. Central side effects were seen in some children who received continuous intrathecal baclofen infusion and included hypotension (two patients), bradycardia (two), apnea or respiratory depression (two), and sedation (one). During a total of 568 months of pump operation there were 10 mechanical complications, including two related to pump or side port failure and eight related to catheter kinks, extrusions, or dislodgment. Pump pocket effusion occurred in five children and a cerebrospinal fluid fistula was seen in one child. Local infection occurred in three children and meningitis in two children. The results demonstrate the potential value of continuous intrathecal baclofen infusion for treatment of severe spasticity of cerebral origin. However, this treatment can result in significant complications and more experience is required before the long-term benefits can be determined.
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PMID:Intrathecally administered baclofen for treatment of children with spasticity of cerebral origin. 928 7

Serial neuroimaging studies in Alexander's disease were obtained on an African-American girl who died at 4z\x years of age. She presented with macrocephaly, psychomotor retardation, spasticity, a seizure disorder, and hydrocephalus. A thorough metabolic evaluation of defined leukodystrophies, including Krabbe's disease, adrenoleukodystrophy, metachromatic leukodystrophy, Canavan's disease, and Leigh disease, was negative. A diagnosis of Alexander's disease was made based on the clinical features and ruling out all other possible causes. It was confirmed by pathologic findings of numerous subpial, subependymal, and perivascular Rosenthal fibers throughout the entire cerebrum. Interestingly, autopsy also identified the stenotic sylvian aqueduct owing to Rosenthal fiber accumulation, explaining the origin of hydrocephalus. The evolution of magnetic resonance imaging findings appears to be unique in this disease.
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PMID:Infantile Alexander's disease: serial neuroradiologic findings. 1217 72

Leigh syndrome (LS) (sub-acute necrotizing encephalomyelopathy) is characterized by symmetric brain lesions occurring mainly in the basal ganglia and associated with variable clinical manifestations such as hypotonia, psychomotor retardation, and feeding difficulties. Patients with LS may develop seizures. Only three patients with LS have been identified in the literature as having West syndrome (WS). We have seen 12 children with LS in the past 20 years, and noticed that as many as five of them developed WS. This report discusses five LS children with WS, comparing them with seven LS children without WS. In all five patients, infantile spasms developed after LS had become evident, in addition to other type(s) of seizures. The onset of LS in all the patients with WS was before 10 months of age. Although not statistically proven, early onset of LS, spasticity, nystagmus, apnea, poor feeding, and cardiac problems seemed to be associated with the development of WS. We were not able to conclude that certain types of symptoms or examination results of patients with LS indicated the development of WS. The association of LS with WS did not markedly influence the prognoses of the children. WS may not be a rare complication of LS, especially in infants under 12 months of age. This report is the first review of LS associated with WS.
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PMID:Leigh syndrome associated with West syndrome. 1276 55

We retrospectively analyzed a case of a 7-month-old infant with a delay of psychomotor development, slow pupillary light reflexes, horizontal nystagmus, spasticity and bilateral optic nerve atrophy. At the end of life there were problems with swallowing. Ventriculography showed widening of the lateral ventricles and atrophy in the frontal lobes. EEG revealed generalized changes. Clinically, leucodystrophy was diagnosed. General autopsy revealed cardiac hypertrophy. Neuropathological picture showed orthochromatic leucodystrophy with some features characteristic of neuropathology of mitochondrial disease: capillary hyperplasia and hypertrophy, spongiosis and symmetrical, bilateral damage of brain stem structures. The last one is characteristic of Leigh syndrome. Electron microscopic evaluation showed abnormal mitochondria, myelin and neurofibrils destruction. Hypertrophy of the heart may be also connected with mitochondrial disease.
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PMID:Infantile mitochondrial leucodystrophy - a case report. 1624 15

In this paper, we describe a distinct clinical subtype of 3-methylglutaconic aciduria. 3-Methylglutaconic aciduria is a group of different metabolic disorders biochemically characterized by increased urinary excretion of 3-methylglutaconic acid. We performed biochemical and genetic investigations, including urine organic acid analysis, NMR spectroscopy, measurement of 3-methylglutaconyl-CoA hydratase activity, cardiolipin levels, OPA3 gene analysis and measurement of the oxidative phosphorylation in four female patients with 3-methylglutaconic aciduria. 3-Methylglutaconic aciduria type I, Barth syndrome, and Costeff syndrome were excluded as the activity of 3-methylglutaconyl-CoA hydratase, the cardiolipin levels, and molecular analysis of the OPA3 gene, respectively, showed no abnormalities. The children presented with characteristic association of hearing loss and the neuro-radiological evidence of Leigh disease. They also had neonatal hypotonia, recurrent lactic acidemia, episodes with hypoglycemia and severe recurrent infections, feeding difficulties, failure to thrive, developmental delay, and progressive spasticity with extrapyramidal symptoms. Our patients were further biochemically characterized by a mitochondrial dysfunction and persistent urinary excretion of 3-methylglutaconic acid.
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PMID:Association of 3-methylglutaconic aciduria with sensori-neural deafness, encephalopathy, and Leigh-like syndrome (MEGDEL association) in four patients with a disorder of the oxidative phosphorylation. 1652 7

The central nervous system (CNS) is, after the peripheral nervous system, the second most frequently affected organ in mitochondrial disorders (MCDs). CNS involvement in MCDs is clinically heterogeneous, manifesting as epilepsy, stroke-like episodes, migraine, ataxia, spasticity, extrapyramidal abnormalities, bulbar dysfunction, psychiatric abnormalities, neuropsychological deficits, or hypophysial abnormalities. CNS involvement is found in syndromic and non-syndromic MCDs. Syndromic MCDs with CNS involvement include mitochondrial encephalomyopathy, lactacidosis, stroke-like episodes syndrome, myoclonic epilepsy and ragged red fibers syndrome, mitochondrial neuro-gastrointestinal encephalomyopathy syndrome, neurogenic muscle weakness, ataxia, and retinitis pigmentosa syndrome, mitochondrial depletion syndrome, Kearns-Sayre syndrome, and Leigh syndrome, Leber's hereditary optic neuropathy, Friedreich's ataxia, and multiple systemic lipomatosis. As CNS involvement is often subclinical, the CNS including the spinal cord should be investigated even in the absence of overt clinical CNS manifestations. CNS investigations comprise the history, clinical neurological examination, neuropsychological tests, electroencephalogram, cerebral computed tomography scan, and magnetic resonance imaging. A spinal tap is indicated if there is episodic or permanent impaired consciousness or in case of cognitive decline. More sophisticated methods are required if the CNS is solely affected. Treatment of CNS manifestations in MCDs is symptomatic and focused on epilepsy, headache, lactacidosis, impaired consciousness, confusion, spasticity, extrapyramidal abnormalities, or depression. Valproate, carbamazepine, corticosteroids, acetyl salicylic acid, local and volatile anesthetics should be applied with caution. Avoiding certain drugs is often more beneficial than application of established, apparently indicated drugs.
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PMID:Central nervous system manifestations of mitochondrial disorders. 1694 41


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