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)

Sphingolipidoses are an heterogeneous group of inherited disorders of lipid metabolism affecting primarily the central nervous system. These disorders occur chiefly in the pediatric population, and the degenerative nature of the disease processes is generally characterized by diffuse and progressive involvement of neurones (gray matter) with psychomotor retardation and myoclonus or of fiber tracts (white matter) with weakness and spasticity. Biochemical research has identified the defects in the sphingolipidoses to specific lysosomal enzymes. For example, Niemann-Pick disease lacks sphingomyelinase; Krabbe's disease lacks galactocerebrosidase; Gaucher's disease lacks beta-D-glucosidase; metachromatic leukodystrophy lacks sulfatase; Tay-Sachs disease lacks hexosaminidase A; and generalized gangliosidosis lacks beta-galactosidase. Although there are no currently available modes of rendering corrective therapy in these disorders, a definitive diagnosis is possible both antepartum as well as postpartum. This information provides a sound and accurate basis for genetic counseling.
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PMID:Sphingolipidoses. 555 2

Dementia, a syndrome of acquired intellectual deterioration, is an etiologically nonspecific condition that can be permanent or reversible. When evaluating demented patients, a careful exposure history will determine the possible role of drugs, metals, or toxins. Physical examination may reveal focal deficits in cases of intracranial mass lesions and spasticity or ataxia of the lower limbs if hydrocephalus is present. Coexistence of dementia and a peripheral neuropathy usually indicates the existence of a toxic or metabolic disorder. Depressed mood, sleep disturbance, anorexia, impotence, constipation, and psychomotor retardation indicate the presence of a depressive syndrome. Asterixis, myoclonus, and postural tremor are common in toxic-metabolic dementias, whereas resting tremor, choreoathetosis, or rigidity occur in progressive extrapyramidal disorder. EEG is focally abnormal in cases of cerebral mass lesions and shows generalized slowing in toxic-metabolic encephalopathies. CT will aid in the identification of hydrocephalus, subdural hematomas, and intracranial mass lesions. A thorough laboratory evaluation including complete blood count, erythrocyte sedimentation rate, electrolytes, blood urea nitrogen and blood sugar, liver and thyroid function tests, serum calcium and phosphorus levels, B12 and folate levels, serum copper and ceruloplasmin, VDRL, chest X-ray, electrocardiogram, and lumbar puncture may demonstrate treatable disorders that are adversely affecting intellectual function. Elderly individuals are particularly susceptible to the effects of toxic or metabolic disorders, and a mild dementia may be exaggerated by relatively minor fluctuations in metabolic status. Treatable causes of dementia should be sought in all demented patients.
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PMID:Treatable dementias. 635 58

Four patients with palatal myoclonus were examined electromyographically. Surface EMG was recorded simultaneously from several myoclonic muscles and the correlation between their rhythmic discharges was shown. The possible existence of a remote influence of palatal myoclonus was tested by recording soleus and anterior tibial H-reflexes and seeking a correlation of their amplitudes with the rhythm of palatal myoclonus. Two cases, both with additional severe spasticity in the legs, showed rhythmic variation of the soleus H-reflex amplitude corresponding with that of their palatal myoclonus. This suggests that the neural mechanism generating the visible myoclonus has much more extensive effects.
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PMID:Palatal myoclonus--its remote influence. 648 85

Autopsy samples were obtained from a 12.5-year-old girl who died with a neurologic disorder consisting of myoclonus, myoclonic epilepsy, spasticity, strabismus, and mild mental retardation but no hepatosplenomegaly. Studies in leukocytes, cultured skin fibroblasts, brain, liver, and spleen of this patient revealed glucosylceramide beta-glucosidase (EC 3.2.1.45, glucocerebrosidase) activity about 10% of controls, and well in the range found in samples from Gaucher disease patients. Extraction of the lipids from liver and spleen with chloroform-methanol (2:1) did not show accumulation of glucosylceramide or other lipid. Examination of the lipids in brain by high performance liquid chromatography revealed the presence of glucosylceramide, which is not found in brain samples from controls. Pathologic examination of the liver and spleen revealed no evidence of Gaucher disease. The brain showed many degenerative lesions and loss of neurons. There was no complementation of glucocerebrosidase activity when the cells from this patient were hybridized with cells from patients with Type 1 or Type 2 Gaucher disease. The reason for the lack of glucosylceramide storage in the liver and spleen has not been determined.
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PMID:Biochemical studies in a patient with subacute neuropathic Gaucher disease without visceral glucosylceramide storage. 685 96

Thirty-eight cases of subacute sclerosing panencephalitis (SSPE) were reviewed. Deterioration in school performance, personality changes, and seizures were common early symptoms. Initial examination frequently showed myoclonus, spasticity, and extrapyramidal dysfunction, and in two-thirds of patients these findings were asymmetrical or focal. Retinitis or papilledema was present on initial examination in 50% of the patients. At last follow-up 24 children had died, with a mean survival of 42 months. Most patients reached a state of severe neurological impairment within 13 months. Subsequent evidence of improvement was noted in 10 children and was sustained in 4. Fifteen patients received antiviral treatment. Ten treated patients died from 5 to 133 months (mean, 58) from onset of their illness, while 15 untreated patients survived a mean of 33 months. Duration of survival appeared to be affected most by treatment with amantadine. Three patients treated with the drug were alive 97 to 139 months after onset of SSPE, and 5 died with a mean survival of 78 months. Five of 6 individuals treated with rifampin died after a mean survival of 27 months. Prolonged remissions occurred only in patients treated with amantadine. Although the number of treated individuals was small, our data suggest that amantadine may affect the natural course of SSPE.
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PMID:Review of 38 cases of subacute sclerosing panencephalitis: effect of amantadine on the natural course of the disease. 743 85

Studies of pathogenetic mechanisms of myoclonus and spinal spasticity have established a strong association between deficient inhibitory glycinergic transmission and pathologic rigidity and tremor. Consistent with known cases in the clinical literature, electrophysiologic data from animal models of myoclonus implicate dysfunction of segmental spinal cord circuitry. The present study sought to further explore pathogenetic mechanisms at the circuit level. In vitro preparations of isolated spinal cord from neonatal rodents allowed for stable recordings of individual cells as well as populations of motoneurons. Blockade of glycine receptors enhanced 5- to 15-Hz sinusoidal oscillations that were synchronous in entire populations of motoneurons as well as along multiple segments of the spinal cord. Oscillations at motoneurons were mediated largely by non-NMDA excitatory synaptic inputs. Blockade of GABAA receptors, and not GABAB receptors, abolished sinusoidal oscillations, suggesting a critical role for GABAA receptors in the premotoneuronal circuitry responsible for generation or transmission of the sinusoidal oscillations. These data offer new insights into possible pathogenetic mechanisms of spinal myoclonus and may help guide future research leading to specific therapies for hyperkinetic movement disorders of spinal origin.
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PMID:Involvement of glycine and GABAA receptors in the pathogenesis of spinal myoclonus: in vitro studies in the isolated neonatal rodent spinal cord. 747 87

We report two families with a disorder, probably autosomal recessive, characterized by tremor of juvenile onset, dystonia, and myoclonus with preserved cognitive, cerebellar, and peripheral nervous system functions. During 4 years' follow-up, mild spasticity appeared. Magnetic resonance imaging (MRI) revealed mild diffuse changes in the white matter. Central conduction times for visual, motor, and sensory systems were all prolonged. Extensive metabolic work-up failed to reveal lysosomal, peroxisomal, mitochondrial, or other metabolic abnormalities.
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PMID:Familial tremulous and myoclonic dystonia with white matter changes in brain magnetic resonance imaging. 756 37

Congenital myoclonus is a widespread neurologic disorder characterized by hyperexcitability, muscular spasticity and myoclonus associated with marked reduction in neural glycine binding sites. The recessive mouse mutation spastic (spa) is a prototype of inherited myoclonus. Here we show that defects in the gene encoding the beta-subunit of the glycine receptor (Glrb) underlie spa: Glrb maps to the same region of mouse chromosome 3 as spa, and Glrb mRNA is markedly reduced throughout brains of spa mice, most likely as a result of an insertional mutation of a 7.1 kilobase LINE-1 element within intron 6 of Glrb. These results provide evidence that Glrb is necessary for postsynaptic expression of glycine receptor complexes, and suggest Glrb as a candidate gene for inherited myoclonus in other species.
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PMID:Glycine receptor beta-subunit gene mutation in spastic mouse associated with LINE-1 element insertion. 792 Jun 30

We report a 21-year-old man with agammaglobulinemia and chronic progressive encephalopathy. The patient was diagnosed as having X-linked agammaglobulinemia at 6 months of age, and gamma globulin supplementation was initiated. He exhibited normal development until he was 11 years old, when he showed a decline in school performance and a personality change. Computed tomography images at that time disclosed diffuse cerebral atrophy. Several generalized tonic-clonic convulsions, myoclonus and spasticity appeared at the age of 13 years. He lost his ability to walk and speak at the age of 17 years old. He is currently 21 years old and displays severe mental deterioration and spastic tetraplegia. Magnetic resonance imaging showed progressive diffuse cerebral atrophy with no change in intensity. The cerebellum and the brain stem were relatively well maintained. Viral isolations were negative and serum antibody titers for rubella, measles, and human immune deficiency virus were not elevated. Our patient's symptoms resemble those previously reported as chronic progressive encephalopathy without viral isolation. This condition may be a complication of agammaglobulinemia. It is possible that the encephalopathy of our patient has the same etiology as that described in the other reports. Further attempts to identify the etiology of the encephalopathy using molecular techniques are necessary.
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PMID:[A case of agammaglobulinemia with chronic progressive encephalopathy]. 795 27

Local injections of botulinum toxin is a well-accepted treatment for focal dystonias, hemifacial spasms and strabismus. Its use by skilled neurologists has been reported to be safe and effective. We report our experience with botulinum toxin injections in 108 patients with various central nervous system disorders. Botox was effective in upper face dystonia (86% improvement), spastic dysphonia (92% improvement), platysma muscle spasms and spasmodic torticollis (range of movement 61%, pain and tension 90%). It was also very effective in a few patients with apraxia of eyelid opening, parkinsonian jaw tremor, teeth clenching, palatal myoclonus and adductor leg spasticity. No serious side effects were recorded. Botulinum toxin is a useful symptomatic treatment for many neurological disorders, and one of the leading mode of treatments in the new subspecialty in neurology called "Interventional neurology."
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PMID:Interventional neurology: botulinum toxin as a potent symptomatic treatment in neurology. 798 70


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