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)

High-dose treatment with pilocarpine hydrochloride, a cholinergic muscarinic agonist, induces seizures in rodents following systemic or intracerebral administration. Pilocarpine seizures are characterized by a sequential development of behavioral patterns and electrographic activity. Hypoactivity, tremor, scratching, head bobbing, and myoclonic movements of the limbs progress to recurrent myoclonic convulsions with rearing, salivation, and falling, and status epilepticus. The sustained convulsions induced by pilocarpine are followed by widespread damage to the forebrain. The amygdala, thalamus, olfactory cortex, hippocampus, neocortex, and substantia nigra are the most sensitive regions to epilepsy-related damage following convulsions produced by pilocarpine. Spontaneous seizures are observed in the long-term period following the administration of convulsant doses of pilocarpine. Developmental studies show age-dependent differences in the response of rats to pilocarpine. Seizures are first noted in 7-12 day-old rats, and the adult pattern of behavioral and electroencephalographic sequelae of pilocarpine is seen in 15-21-day-old rats. During the third week of life the rats show an increased susceptibility to the convulsant action of pilocarpine relative to older and younger animals. The developmental progress of the convulsive response to pilocarpine does not correlate with evolution of the brain damage. The adult pattern of the damage is seen after a delay of 1-2 weeks in comparison with the evolution of seizures and status epilepticus. The susceptibility to seizures induced by pilocarpine increases in rats aged over 4 months. The basal ganglia curtail the generation and spread of seizures induced by pilocarpine. The caudate putamen, the substantia nigra, and the entopeduncular nucleus govern the propagation of pilocarpine-induced seizures. The antiepileptic drugs diazepam, clonazepam, phenobarbital, valproate, and trimethadione protect against pilocarpine-induced convulsions, while diphenylhydantoin and carbamazepine are ineffective. Ethosuximide and acetazolamide increase the susceptibility to convulsant action of pilocarpine. Lithium, morphine, and aminophylline also increase the susceptibility of rats to pilocarpine seizures. The pilocarpine seizure model may be of value in designing new therapeutic approaches to epilepsy.
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PMID:Review: cholinergic mechanisms and epileptogenesis. The seizures induced by pilocarpine: a novel experimental model of intractable epilepsy. 264 33

Monkeys inflicted with specific unilateral electrolytic lesions in the upper brain stem developed extrapyramidal disorders. Hypokinesia of the limbs was associated contralaterally with a lesion of the substantia nigra and depletion of striatal dopamine. Choreiform movements were observed in animals that had, contralaterally, a lesion severing the most dorsomedial fibres of the cerebral peduncle and the rubro-tegmentospinal tract, associated with depletion of striatal serotonin. Monkeys showing sustained postural tremor and hypokinesia had lesions affecting these three tracts contralaterally and loss of striatal dopamine and serotonin on the lesion side. Of many drugs tested, only harmaline and harmine affected the dyskinesias. The nigrostriatal fibres appear to be dopaminergic; the cerebral peduncular (dorsomedial) fibres, serotoninergic. The role of striatal dopamine and serotonin in the control of normal movements and posture of the limbs represents the first directly demonstrated function of these amines in the central nervous system.
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PMID:Neurochemical bases of tremor and other disorders of movement. 438 Mar 39

The effects of neonatal exposure of rats to chlordecone were assessed in the preweaning period of development. On day 4 postpartum, pups received a SC injection (20 microliter) of either dimethylsulfoxide (DMSO) or 1 mg/pup of chlordecone dissolved in DMSO. Body weights on days 14 and 21 were slightly (9-14%), but significantly, depressed in both sexes by the neonatal chlordecone exposure. Whole body movements, monitored via a spectral analyzer, indicated a significant high frequency tremor in the chlordecone-exposed pups on postnatal days 10, 14, and 18. The auditory startle response to a 4 kHz, 110 dB (SPL) tone was examined on days 12, 16, and 20. A significant enhancement of startle responsiveness was noted in chlordecone-exposed pups relative to vehicle-injected littermates; this effect was localized primarily at 16 days of age and in the female pups. Evaluation of undifferentiated motor activity, as assessed by testing individual pups in the presence of homecage shavings, indicated significant chlordecone-induced hypoactivity in both sexes on postnatal day 15. Hypoactivity persisted through 21 days of age in the female, but not male, chlordecone-exposed pups. This neurotoxic profile of tremor, depressed body weight, and altered responsiveness to novel/stressful environments is detectable in early life and is similar to that observed when adult rats are exposed to chlordecone. The profile also bears similarity to the primary signs and symptoms of chlordecone exposure in adult humans. Collectively, the present observations offer a tentative working model for the further investigation of the developmental neurotoxicity of chlordecone.
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PMID:Evaluation of neonatal chlordecone neurotoxicity during early development: initial characterization. 620 54

Three patients with sporadic amyotrophic lateral sclerosis (ALS) presented with a history of backward falls. Impaired postural reflexes and retropulsion accompanied clinical features of ALS. Hypokinesia, decreased arm swing, and a positive glabellar tap were noted in two of these three patients. Cognitive impairment, tremor, axial rigidity, sphincter dysfunction, nuchal dystonia, dysautonomia, and oculomotor dysfunction were absent. Brain MRI disclosed bilateral T2 weighted hyperintensities in the internal capsule and globus pallidus in one patient. Necropsy studies performed late in the course of ALS have shown degeneration in extrapyramidal sites-for example, the globus pallidus, thalamus, and substantia nigra. Clinically, backward falls and retropulsion may occur early in ALS. This may reflect extrapyramidal involvement.
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PMID:Extrapyramidal involvement in amyotrophic lateral sclerosis: backward falls and retropulsion. 1040 93

In Parkinson disease patients who receive long-term antiparkinsonian medication, their original symptoms of rigidity, tremor and related motor disturbances markedly improve or disappear. However, the condition is still far from satisfactory in terms of maintaining independence in daily life activities even in these patients in whom the drug treatment is for improving motor disturbances. The reason is that they show abnormal behavior characterized by "spending the entire day in an idle state, which is perceived as laziness."This behavior is very annoying for the patient and the family. Despite the excellent effectiveness of drug treatment, this propensity toward idleness in mental and motor functions is not improved. Despite the denial of the depressive state and the absence of obvious cognitive disorder, such patients lack ambition and spend their time idly. However, although their motor function remains subliminal, such patients can carry out motor activities when the situation requires, but usually they do not have the drive to move. If we use the current nosological descriptions, the former is called "bradyphrenia" or psychic akinesia or slowness of thinking and the latter is called "akinesia". Akinesia is composed of two cardinal elements "bradykinesia" and "hypokinesia". Bradykinesia is the evaluation of quality of appeared motor behavior, and hypokinesia is the poverty of movement behavior. These two symptoms differ essentially. Hypokinesia is much more essential and is a cardinal element of akinesia. It indicates that the current drug treatment is ineffective for the improvement of hypokinesia and bradyphrenia. That is, these symptoms are a result of a dysfunction different from that causing residual motor symptoms or a result of other additional dysfunctions developing during the pathophysiological course of the disease. The dopamine (DA) system of the dorsal striatal pathway projecting from the substantia nigra pars compacta (A9) to the dorsal part of the striatum (motor striatum) functions in the control of speed and dexterity of movement. On the other hand, the DA system through the medial forebrain bundle projecting from the ventral tegmental area (VTA-A10) to the nucleus accumbens, ventral striatum (limbic striatum) and the cortex is associated with hypokinesia and bradyphrenia. This association can be confirmed by a long-term follow-up of Parkinson disease patients and experimental animal models lesioned in the ventral DA pathway (mesolimbic and mesocortical pathways).
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PMID:[Mesolimbic and mesocortical pathways in Parkinson disease]. 1788 76

A dopaminergic deficiency in patients with Parkinson's disease (PD) causes abnormalities of movement, behaviour, learning, and emotions. The main motor features (ie, tremor, rigidity, and akinesia) are associated with a deficiency of dopamine in the posterior putamen and the motor circuit. Hypokinesia and bradykinesia might have a dual anatomo-functional basis: hypokinesia mediated by brainstem mechanisms and bradykinesia by cortical mechanisms. The classic pathophysiological model for PD (ie, hyperactivity in the globus pallidus pars interna and substantia nigra pars reticulata) does not explain rigidity and tremor, which might be caused by changes in primary motor cortex activity. Executive functions (ie, planning and problem solving) are also impaired in early PD, but are usually not clinically noticed. These impairments are associated with dopamine deficiency in the caudate nucleus and with dysfunction of the associative and other non-motor circuits. Apathy, anxiety, and depression are the main psychiatric manifestations in untreated PD, which might be caused by ventral striatum dopaminergic deficit and depletion of serotonin and norepinephrine. In this Review we discuss the motor, cognitive, and psychiatric manifestations associated with the dopaminergic deficiency in the early phase of the parkinsonian state and the different circuits implicated, and we propose distinct mechanisms to explain the wide clinical range of PD symptoms at the time of diagnosis.
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PMID:Initial clinical manifestations of Parkinson's disease: features and pathophysiological mechanisms. 1990 11

Hypokinetic-rigid syndrome (HRS) or "parkinsonism" is rare in children. From a clinical point of view it is characterised by a group of signs in which hypokinesia (decreased number of movements), bradykinesia (slowness of movements), rigidity and rest tremor are the fundamental traits. Nervous system infections, immunomediated encephalitis, hypoxia and some drugs have been described as acquired or secondary causes of HRS in the paediatric age. Inborn errors of metabolism (IEM) comprise and important group regarding genetic causes. Main diseases causing HRS in children are neurotransmitter (biogenic amines) defects, metal storage diseases, energy metabolism disorders and lysosomal diseases. In general, in IEM, the HRS is associated to other neurological signs such as dykinesias, pyramidal signs, and psychomotor delay, is very rare in the neonatal period, tends to be more frequent in advanced stages of progressive diseases, and may respond to specific therapies. In particular, l-dopa + carbidopa can be a very effective treatment in neurotransmitter defects, whereas other disorders such as Wilson disease and some particular lysosomal disorders have different therapeutic possibilities. Furthermore, other genetic conditions in dopa-responsive and non-responsive HRS should be also considered, especially in juvenile parkinsonism. Through this review, a practical orientation for paediatric neurologists concerning clinical clues, diagnostic procedure and treatment of metabolic HRS will be provided.
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PMID:Hypokinetic-rigid syndrome in children and inborn errors of metabolism. 2161 60