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 decompression sickness and during some surgical procedures, air emboli that form sometimes cause serious damage if the gas bubbles find their way to the vital organs. Paralysis of the spinal cord is one of the most serious manifestations induced by air emboli. Exposure to compression chambers is effective in air emboli treatment, but availability of chambers is inadequate and the treatment is lengthy. Until now there has been no fully effective injectable agent that can remedy the damage caused by air embolization. In this work levodopa was chosen as an injectable drug that might help to improve recovery from experimental paraplegia because of the reported effects of levodopa on muscle tone, spasticity and locomotion. To induce air emboli, the descending aorta of rats was chronically cannulated. Two weeks later, after full recovery from surgery, air was injected through the chronically implanted cannula into unanesthetized rats (0.35 ml of air per 100 g, during 4 sec). The paraplegia (paralysis of both hind legs) was manifested 2-10 minutes later. Only animals that had total paraplegia, without any sensation, were used in the experiments. Levodopa was administered 2 minutes after paraplegia was established. The levodopa treatment was repeated each day during one week. After six days, ten levodopa treated (intra-arterially) animals in a group of twelve and six levodopa treated (intraperitoneally) animals in a group of eight recovered completely from paraplegia. In control groups only three from thirteen (untreated), or two from twelve (solvent administration) animals recovered from paraplegia.
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PMID:Recovery from experimental paraplegia after levodopa administration. 96 98

Four male patients and one female patient of a new family with Joseph disease are reported. Their disease was characterized by autosomal dominant inheritance, bulging eyes, rigidity and spasticity of the lower extremities, dystonia, and bradykinesia. Cerebrospinal fluid homovanillic acid level was markedly reduced. Levodopa improved dystonia. Magnetic resonance imaging revealed mild atrophy of the frontal lobe and the cerebellum and marked atrophy of the lenticular nucleus and the brain stem. Polysomnographic studies revealed non-rapid eye movement stage central type sleep apnea syndrome. This is the first report using magnetic resonance imaging and sleep apnea studies of Joseph disease.
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PMID:A new family with Joseph disease in Japan. Homovanillic acid, magnetic resonance, and sleep apnea studies. 270 4

We have investigated the effects of various dopamine (DA) agonists on induction of abnormal involuntary movements (AIM) in a group of monkeys which had denervated nigro-striatal DA neurons for 10-14 years rendered by a unilateral surgical ventromedial tegmental (VMT) lesion of the brainstem. The surgical lesions were placed when the monkeys were 2-4 years old. The administration of mixed DA agonists, such as L-DOPA, apomorphine (Apo) and abeorphine 201-678, elicit a self-mutilative biting behavior (SMB) of the forelimb digits contralateral to the lesion, and spasticity of the contralateral hindlimb. These dysfunctions resemble, in some aspects, the neurological disturbances associated with Lesch-Nyhan syndrome. The SMB behavior was elicited by mixed DA agonists which predominantly stimulate D1, but not D2 DA receptors, and was prevented or abolished by the D1 DA antagonist SCH 23390 or by the D1 and D2 DA antagonist fluphenazine (Flu), but not by the D2 antagonist (+/-)sulpiride. These results suggest that DA agonist-induced SMB behavior is mediated by D1 and/or by both D1 and D2 DA receptor pathways. To study the relationships between HPRT, the defective enzyme in Lesch-Nyhan syndrome, and the DA neuronal systems, we have measured the effects of nigro-striatal DA degeneration and intrastriatal neuronal degeneration on HPRT activity. The unilateral 6-OHDA-induced nigro-striatal DA degeneration does not significantly alter the HPRT activity on the lesioned side of the striatum, while the quinolinic acid-induced intrastriatal neuronal degeneration significantly reduces the enzyme activity. These results suggest that HPRT is localized on intrastriatal neurons which are also known to contain DA receptors. It is postulated that HPRT deficiency in Lesch-Nyhan syndrome results in abnormal guanine nucleotide metabolism which may affect the regulation of DA receptors.
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PMID:Dopamine agonist induced self-mutilative biting behavior in monkeys with unilateral ventromedial tegmental lesions of the brainstem: possible pharmacological model for Lesch-Nyhan syndrome. 293 64

This report describes a case of metrizamide encephalopathy with persistent disturbance of consciousness and extrapyramidal symptoms. These two conditions have rarely been reported among the various adverse effects of metrizamide. An 11-year-old girl had been in almost good health until she was ten years old, at which time she received a ventriculo-peritoneal shunt operation, suffering from hydrocephalus of unknown etiology. At the age of eleven, she was admitted to our hospital due to hydrocephalus recurrence. She was examined by metrizamide shunt-gram (1200 mg iodide/4 ml). On the next day, she became drowsy. The CT scan disclosed the periventricular penetration of metrizamide into the medial part of the thalamus and the caudate nucleus. Thirteen days later, disturbance of consciousness continued, and extrapyramidal symptoms, that is, rigo-spasticity and postural tremor, were observed. Oral administration of L-threo-DOPS, the direct precursor of noradrenaline, was effective against the persistent disturbance of consciousness and L-DOPA was effective against the extrapyramidal symptoms. She soon recovered almost to normal and no neurological deficit remained. We thus conclude that the CT scan findings and effects of L-threo-DOPS and L-DOPA suggest that metrizamide encephalopathy in this case were respectively due to its periventricular penetration into the medial part of the thalamus and the caudate nucleus, and the resultant deficiency of the ascending noradrenergic reticular activating system and the nigrostriatal dopaminergic system.
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PMID:[Metrizamide encephalopathy in a child with hydrocephalus--effects of L-threo-DOPS on persistent disturbance of consciousness and L-dopa on extrapyramidal symptoms]. 314 37

In this review, the authors present a critical overview of the historical development, indications, complications, operative techniques, and results of procedures for the alleviation of the major dyskinesias. Emphasis is placed upon recent refinement of technique, particularly stereotaxis, as well as neurophysiologic stimulation and recording, computerized tomographic scanning (CT) and magnetic resonance imaging (MRI). Specific disorders that may be amenable to surgical therapy include spasticity secondary to spinal cord pathology, cerebral palsy, and multiple sclerosis; the tremor and rigidity of Parkinson's disease; essential tremor; dystonia; spasmodic torticollis; post-traumatic and postinfarction intention tremor; cerebral palsy with tremor; hemiballismus; myoclonus; and dyskinesias induced by L-DOPA.
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PMID:Neurosurgical management of spasticity, rigidity, and tremor. 332 80

1. In order to study fusimotor control in reduced preparations, soleus muscle spindle afferents were recorded in premammillary decerebrate cats (n = 15) during crossed extensor reflexes and, after spinalization, during locomotion produced by either clonidine or L-beta-3,4-dihydroxyphenylalanine (L-DOPA). The soleus muscle was oscillated sinusoidally (0.25 mm, 4 Hz) and the afferent mean firing rate and modulation were calculated. An increase in firing rate was assumed to arise from activity in dynamic gamma-motoneurones (dynamic gamma-drive) when associated with an increase in modulation to stretching, and in static gamma-motoneurones (static gamma-drive) when modulation decreased. 2. At rest in all preparations the firing rate and modulation in primary muscle spindle afferents were generally much higher than after de-efferentation (ventral root section), suggesting a predominant dynamic gamma-drive. Clonidine decreased and even eliminated this presumed resting gamma-drive in many afferents, both in the decerebrate (7 of 8) and the spinal (6 of 18) state. This effect on gamma-drive may account, at least in part, for its suppressive effect on spasticity in humans. 3. When locomotion commenced in clonidine-treated spinal cats, primary afferents generally fired with much higher mean rates (+121%) and lower sensitivities (-32%), suggesting a large increase in static gamma-drive (possibly accompanied by a small decrease in dynamic gamma-drive). These high rates were usually maintained tonically throughout the step cycle. However, a third of the afferents were silenced during locomotor contractions, and de-efferentation had no significant effect on their firing rates. Thus, for some spindles alpha-activity can occur without significant gamma-drive. 4. During locomotion in L-DOPA-treated spinal cats the inferred static gamma-drive only occurred phasically, coactivated with the EMG, though it could precede the EMG by 100-500 ms. In the flexion phase both the afferent rate and modulation were lower than before locomotion, suggesting a lack of effective gamma-drive. 5. Crossed extensor reflexes in decerebrate cats also produced a substantial increase in primary afferent firing rate (+187%) and decrease in sensitivity (-37%), again suggesting increased static gamma-drive (n = 18). This gamma-drive was largely independent of EMG activity and often occurred without alpha-activity. The mean firing rate of secondary muscle spindle afferents increased significantly during locomotion (with L-DOPA) and crossed extensor reflexes, again indicating increased static gamma-drive. Clonidine reduced or eliminated the gamma-drive in seven of eight afferents during crossed extensor reflexes. 6. In conclusion, although there are some common features, such as a predominant static gamma-drive in all walking preparations, the pattern of static and dynamic gamma-drive is not closely linked to alpha-activity under the conditions studied. As well as gamma-drive without alpha-activity, we have shown for the first time that alpha-motoneurones can be activated without significant gamma-drive to many spindles during behavioural tasks.
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PMID:Regulation of soleus muscle spindle sensitivity in decerebrate and spinal cats during postural and locomotor activities. 888 86

We studied the clinical features and molecular genetics of a family, afflicted with a form of atypical parkinsonism, originating from the Madeira Islands of Portugal. We examined four affected individuals and reviewed clinical information on one other affected family member. Mean age at onset was 31 years. Parkinsonism (akinesia, rigidity, gait disturbance) was the most prominent feature in advanced disease. Levodopa responsiveness with peak-dose dyskinesia was present in one individual. Initial symptoms and other clinical features were variable and included other extrapyramidal signs (dystonia, action tremor of the limbs and bulbar muscles, synkinesis), ophthalmologic abnormalities (ptosis, slow saccades, progressive external ophthalmoplegia, hypometric saccades, saccadic pursuit movements), speech abnormalities (dysarthria, hypernasality), cortical impairment (dementia, frontal lobe dysfunction, palilalia, perseveration), minor cerebellar signs (dysmetria, gait ataxia), pyramidal abnormalities (spasticity, hyperreflexia), and peripheral nervous system abnormalities (propioceptive loss, areflexia, distal weakness, atrophy). The length of trinucleotide repeats in the MJD1 gene was in the normal range for all affected individuals.
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PMID:Atypical parkinsonism in a family of Portuguese ancestry: absence of CAG repeat expansion in the MJD1 gene. 915 59

Huntington's disease is an autosomal dominant progressive neurodegenerative disorder characterized by involuntary movements, cognitive decline, and behavioral disorders leading to functional disability. In contrast to patients with adult onset, in which chorea is the major motor abnormality, children often present with spasticity, rigidity, and significant intellectual decline associated with a more rapidly progressive course. An unusual early-onset Huntington's disease case of an 11-year-old boy with severe hypokinetic/rigid syndrome appearing at the age of 2.5 years is presented. Clinical diagnosis was confirmed by polymerase chain reaction study of the expanded IT-15 allele with a compatible size of 102 cytosine-adenosine-guanosine repeats L-Dopa mildly ameliorated rigidity, bradykinesia, and dystonia. We conclude that Huntington's disease should be included in the differential diagnoses of regressive syndromes of early childhood.
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PMID:Unusual early-onset Huntingtons disease. 1288 81

A 12 year old boy with gradually worsening global developmental delay was diagnosed and managed as quadriplegic cerebral palsy since child-hood. Subsequent evaluation revealed marked dystonia over spasticity leading to suspicion of Segawa syndrome. Dramatic improvement in clinical condition followed after therapy with low dose L-Dopa.
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PMID:Dopa-responsive dystonia (Segawa syndrome). 1689 85

We describe a unique presentation of autosomal recessive (AR) GTP cyclohydrolase I (GTPCH) deficiency, with severe CNS involvement but without hyperphenylalaninemia. A male infant presented with progressive spasticity, dystonia and oculogyric episodes. Blood phenylalanine levels were persistently normal: whereas an oral phenylalanine loading test revealed impaired phenylalanine clearance. CSF neopterin and tetrahydrobiopterin (BH(4)) were low, homovanillic acid marginally low and 5-hydroxyindoleacetic acid normal. Fibroblasts showed decreased GTPCH enzyme activity. A homozygous novel mutation of GCH1, p.V206A, was identified. On treatment (BH(4), L-Dopa/Carbidopa and 5-hydroxytryptophan), motor development improved. Mutational analysis provided neonatal diagnosis of a younger brother who, after 18 months on treatment, shows normal development. AR GTPCH I deficiency can present without hyperphenylalaninemia and with normal or subtle CSF neurotransmitter profiles. Testing for GTPCH deficiency should be considered for patients with unexplained neurological symptoms and extrapyramidal movement disorder.
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PMID:Autosomal recessive GTP cyclohydrolase I deficiency without hyperphenylalaninemia: evidence of a phenotypic continuum between dominant and recessive forms. 1827 79


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