Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Postural or Parkinson-like tremor, which results from the impairment of mechanisms which are predominantly lateralized in the brain, is most likely related to the combined impairment of the dopaminergic nigrostriatal pathway and the corresponding rubro-olivo-cerebello-rubral loop (without excluding the possiblity that other nervous mechanisms interconnected with these structures may represent an alternative disturbance). The integrity of the internal division of the pallidum and the ventrolateral area of the thalamus and their efferent fibers as well as the motor cortex and certain of its cortico-subcortico-spinal pathways (Figures 1 and 2) is apparently an essential feature for the elaboration of the rhythmic bursts associated with the appearance of postural tremor. The integrity of the spinal sensory roots and the rubro-tegmentospinal tract is not a prerequisite for the expression of postural tremor, a condition which seems essential for the production of rigidity. The latter facts suggest that the disturbances which subserve these two types of motor impairment, often concomitantly present in Parkinsonism, partially involve the impairment of different mechanisms although the loss of the DA fibers originating in the substantia nigra and ending in the neostriatum (Figure 1) appears to represent a disturbance common to both types of disorders. Bradykinesia which may be associated with an impairment of catecholamine metabolism (and more especially the neostriatal DA mechanisms) on both sides of the brain may also result from bilateral lesions of the pallidum or of its outflow corresponding, in the main, to the pallidothalamic fibers ending in the ventrolateral thalamus. The latter types of lesion most likely exclude the influence of the monoaminergic, cholinergic and gabaminergic activities normally originating in the striopallidal system and influencing the activity transmitted to other CNS mechanisms. Severe akinesia, however, apparently depends on more profound and generalized disturbances of brain monoamine metabolism with or without the involvement of other ill-defined mechanisms. At any rate the impairment of the brain DA mechanisms (and especially those of the neostriatum) seems to represent a major feature in the production of the Parkinsonian type of akinesia. Further work is needed to establish the relative importance of the loss of catecholaminergic mechanisms other than those of the neostriatum in the production of akinesia.
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PMID:Physiopathology of experimental Parkinsonism in the monkey. 80 27

Parkinsonian postural tremor and rigidity most likely involve the disruption of the dopaminergic (DA) nigrostriatal mechanisms and the corresponding rubro-olivo-cerebello-rubral loop without excluding the involvement of related dentato-rubral and dentato-thalamic nervous fascicles. The integrity of the magnocellular division of the red nucleus and of the rubrotegmentospinal pathway, however, is apparently essential for the expression of rigidity. Akinesia most likely results from the bilateral involvement of brain stem catecholaminergic (CA) mechanisms including the DA nigrostriatal pathways. Finally the integrity of the pallidothalamic fibers seems to represent an essential feature for the improvement of these motor disorders by DA agonists, suggesting that certain of these agents, such as apomorphine, exert their main effects through the neostriatal DA receptors.
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PMID:Parkinsonian akinesia, rigidity and tremor in the monkey. Histopathological and neuropharmacological study. 81 42

A 66-year-old man (case 1) and a 71-year-old woman (case 2) showed systemic degeneration of the globus pallidus, substancia nigra, subthalamic nucleus, centrum medianum thalami and at times, superior colliculus in the midbrain. In the pallido-nigral system, neuronal loss was severe in both cases and an increase of pigment and granular spheroids was marked in case 2, less in case 1. Electron-microscopically, the spheroids consisted of aggregates of highly dense material, often membrane-bound, and varying amounts of groups of loosely packed filaments. Clinical symptoms were stereotyped and unique, showing severe akinesia, no rigidity in the limbs, no tremor but retropulsions, upward gaze palsy, dysarthria, dysphagia and later, nuchal stiffness. Nosological identification is discussed.
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PMID:Pallido-nigro-luysial atrophy associated with degeneration of the centrum medianum. A clinicopathologic and electron microscopic study. 84 97

The urinary excretion of free dopamine in 37 untreated parkinsonian patients correlated negatively with the severity of rigidity and akinesia (p less than 0.025) and with total neurologic deficit (p less than 0.05). In a parallel study of psychiatric patients, those with the lowest levels of urinary free dopamine before treatment were the most vulnerable to, and developed the most severe, secondary parkinsonian rigidity (p less than 0.005), akinesia (p less than 0.05), and total deficit (p less than 0.01) when they were subsequently treated for two weeks with trifluoperazine. In neither study was there a significant correlation between free urinary dopamine and tremor. These studies directly associate the level of free dopamine in the urine with the severity of the parkinsonian syndrome. Therefore, although many peripheral sources contribute to urinary free dopamine, a small decrease in the level may actually reflect the severity of the disturbance of central dopamine metabolism and the known deficiency of dopamine in the neurons of the parkinsonian brain.
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PMID:The Parkinsonian syndrome and its dopamine correlates. 93 Jul 45

Rigidity in Parkinson patients can be easily quantitated by determining net work required to passively flex and extend the forearm through an arc of 100 degrees. Rigidity thus measured can be subdivided into two very distinct types, resting and activated. Resting rigidity, measured while the patient is relaxed, responds to all effective therapeutic agents and correlates closely to degree of clinical improvement. Activated rigidity, measured during voluntary activity, is not relieved by any presently available medical treatment. It remains unchanged at pre-therapy levels even in patients who may temporarily appear to have dramatic improvement in clinical symptomatology. Longitudinal measurements made in hundreds of parkinson patients over intervals ranging from 5 to 15 years show continuing high levels of activated rigidity through the entire period of study. In marked contrast to our wide experience with parkinson patients is a single, well documented case of Wilson's disease who appears to have recovered completely both by clinical examination and by all of our machine measurements. This patient had high levels of extrapyramidal deficit, repeatedly measured over a period of four months when penicillamine therapy was being investigated. He then suddenly reverted to normal and returned to full time employment. High values of resting rigidity activated rigidity, akinesia and resting tremor all reverted to normal and have remained normal for the past 6 years. The implication of this study is that L-dopa and related treatments only mask the symptomatology of Parkinson's disease and are not retarding the underlying pathological process. Penicillamine, on the other hand, probably does relieve the destructive process in Wilson's disease and may in early cases, permanently relieve the extrapyramidal dysfunction.
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PMID:Failure of L-dopa to relieve activated rigidity in Parkinson's disease. 93 Jul 49

Twenty-two patients with Parkinsonism were treated with levoamphetamine and 12 of these with dextroamphetamine. Levoamphetamine resulted in a significant improvement in disability from Parkinsonism, although the reduction in total disability, tremor, akinesia, and rigidity scores was slight (ca 20 percent). Dextroamphetamine in lower dosage also reduced disability by some 17 percent. The most disabled patients, including those also on levodopa, showed the greatest response to amphetamines. Previously, amphetamines have been reported to be a selective treatment for the oculogyric crises of post-encephalitic Parkinsonism. Amphetamines are thought to cause the release of catecholamines from central neurones. Their action in Parkinson's disease may be limited because of pre-existing striatal dopamine deficiency. Side-effects of amphetamines, anorexia, and CNS stimulation are different from those caused by levodopa in patients with Parkinson's disease.
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PMID:Amphetamines in the treatment of Parkinson's disease. 109

Eighteen patients with parkinsonism were treated with a combination of L-dopa and peripheral decarboxylase inhibitor, L-alphahydrazinomethyldopa (MK-486). Modification of L-dopa effect by MK-486 was also studied in parkinsonian patients as well as in cats. (1) Concentrations of dopa and dopamine in plasma and brain were measured in cats following intraperitoneal injection of L-dopa alone (100 mg/kg) or combined with MK-486 (10 mg/kg). Dopa levels in plasma and brain in the combination with MK-486 were three times as high as in L-dopa alone. Dopamine levels in caudate nucleus and putamen were increased nearly fourfold with the combination. (2) Plasma dopa and dopamine levels were measured in parkinsonian patients. Clinical pharmacological studies disclosed that a 1 : 10 ratio of MK-486 to L-dopa in dosage was preferable. (3) Maximum plasma dopa levels with the combination were four times those following L-dopa alone. Plasma dopa sustained a high level over a period of five hours. MK-486 markedly reduced plasma levels of dopamine. (4) There was no significant difference in dopa and dopamine levels in cerebrospinal fluid between L-dopa alone and a combination of MK-486, but dopamine levels in the CSF were still high at four hours after the combination of MK-486. (5) In clinical studies of eighteen patients with parkinsonism, the effectiveness of the combination therapy (mean dosage of L-dopa: 750 mg/day) was observed in all cases. Marked improvement was noted in 10 cases out of 15 (67%) with akinesia, in 12 cases out of 17 (71%) with rigidity and in six cases out of 14 (43%) with tremor. Maximum plasma dopa levels were higher in those cases with marked improvement, and were highest in patients with diskinesias as a side effect. (6) An addition of vitamin B6 did not show adverse effects. (7) Transient nausea and vomiting as a side effect, less severe than those experienced with L-dopa alone, were noted in five cases (28%). Dyskinesias in extremities, face, mouth and tongue were observed in six cases (33%). These dyskinesias were seen in a high percentage of cases with marked improvement and were never observed in the extremities contralateral to the side of thalamotomy.
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PMID:L-dopa therapy combined with peripheral decarboxylase inhibitor (MK-486) in Parkinsonism. 115 13

Bilateral injection of 6-hydroxy-dopamine (6-OH-DA) (8mug/4mul) into the substantia nigra causes a significant decrease of the dopamine content in the nucleus caudatus. The intraventricular application of 6-OH-DA (250 mug/10 mul) induces a considerable decrease of dopamine in the caudate nucleus as well as in the globus pallidus and in the medial septal region. Simultaneous changes in norepinephrine content are less spezific. It has to be assumed that there are dopaminergic nerve endings in the glubus pallidus not originating in the substantia nigra. Only after intraventricular applications of 6-OH-DA s short-term and reversible reduction of oxotremorin-induced tremor has been observed. Lesions of the nigrostriatal pathway cause an impairment of motility, probably elicited by rigidity and akinesia. These symptoms correlate better than the tremor to biochemical changes following nigro-striatal pathway lesions.
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PMID:Effects of oxotremorine after nigrostriatal lesions in rats. 116 22

A progressive deterioration in clinical state was noted in more than half of a group of 87 patients with parkinsonism treated with dopa for 4 to 6 years. The pattern of this deterioration is often quite particular: frequency of troubles with walking, falls, predominance of akinesia in certain motor functions, inconstant recurrence of tremor or rigidity. Some intellectual deterioration is sometimes seen, more common in those patients who had suffered episodes of mental confusion. 11 patients died. It may, however, be hoped that the average life expectancy will increase.
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PMID:[The deterioration of patients with parkinsonism treated with L-dopa]. 119 72

Based on comparative clinical and morphometric studies in 45 autopsy cases of Parkinson's disease (PD), 27 clinically presenting with akinesia and rigidity (AR-type), 18 with predominant resting tremor (T-type), the neurobiological basis of the major clinical subtypes in PD is discussed. The AR-type showed higher neuronal losses in locus coeruleus (LC) and in medial and lateral parts of substantia nigra (SNM, SNL), suggesting lesion patterns different from the T-type. More severe cell loss in the serotonergic dorsal raphe nucleus was observed in PD patients with depression than in non-depressed ones. Demented PD subjects showed higher cell loss in SNM than non-demented ones indicating dysfunction of the mesocortical dopamine system, and significantly more severe Alzheimer lesions in isocortex and hippocampus. These and other recent data from the literature indicate that some major clinical features of PD are related to lesions of distinct neuronal systems.
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PMID:Clinico-pathological correlations in Parkinson's disease. 132 May 31


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