Motor functions

Signs and Symptoms Narcosis Behavioral changes decrease in motor functions ... 

The nigrostriatal system is predominantly involved in motor control, which is particularly evident in Parkinson s disease (PD), where a progressive loss of these neurons results in loss of motor function. In the early stages of the disorder, the motor impairment can be reversed by the administration of the dopamine precursor l-DOPA (L-3,4-dihydroxyphenylalanine), which bypasses the need for TH in dopamine... 

Genetic disruption of dopamine synthesis in mice lacking TH shows that dopamine is not essential for development. However, dopamine deficient mice do not survive long after weaning unless treated with l-DOPA. These mice display severe aphagia and adipsia and loss of motor function. While these mice have a major reduction in dopamine levels some residual dopamine can be detected that is generated through the action of tyrosinases. 

At low doses, ketamine may result in impairment of attention, learning ability, and memory, and at high doses it has been associated with delirium, amnesia, impaired motor function, hypertension, depression, and respiratory depression (Krystal et al. 1994). Another mechanism of action appears to be a blocking of the reuptake of catecholamines. This effect leads to an increase in heart rate and blood pressure (Reich and Silvay 1989). 

Many tests have been devised to provide quantitative measures of behavioral disturbances caused by neurotoxic chemicals. Tests have been devised that assess the effects of chemicals on four behavioral functions (D Mello 1992). These are sensory, cognitive, motor, and affective functions. However, because the entire nervous system tends to work in an integrated way, these functions are not easily separable from one another. For example, the outcome of tests focused on sensory perception by rats may be influenced by effects of the test chemical on motor function. 

Control of motor function Nigrostriatal tract from substantia nigra (A9) Animals Stereotypy. Rotation if one tract is lesioned Humans Induces dyskinesias Effective in Parkinsonism Animals Catalepsy Humans Reduces dyskinesias Induces Parkinsonism Mainly D2 some Di ... 

People with Parkinson s disease show a specific degeneration of the nigrostriatal tract so DA must be linked in some way to the control of motor function. It is also known that an imbalance of DA function on the two sides of the rat brain, either by stimulation or lesion of one SN, causes off-line or rotational movement (Ungerstadt and Arbuthnott 1970). This is best shown some days after 6-OHDA lesion of one substantia nigra and its nigrostriatal pathway when systemic apomorphine (DA agonist) causes animals to turn away from the lesioned side (contraversive), presumably... 

Another indication of the importance of DA in motor control is the observation that in humans its precursor levodopa, and DA agonists like bromocriptine, not only overcome the akinesia of Parkinsonism but in excess will actually cause involuntary movements, or dyskinesia (Chapter 14). Also it is well known that DA antagonists like chlorpromazine and haloperidol produce Parkinsonian-like symptoms in humans (and catalepsy in animals) and, as indicated above, reduce the dyskinesia of Huntington s Chorea. Thus DA seems to sit on a knife edge in the control of motor function (Fig. 7.8). 

Figure 7.8 Dopamine and motor function. When nigrostriatal dopamine activity is normal so is motor function. Any reduction in this DA activity, as in Parkinson s disease, results in reduced motor activity, i.e. akinesia. By contrast, too much DA activity, as in Huntington s Chorea, produces abnormal motor function, i.e. dyskinesia. The latter may be controlled by neuroleptic drugs (DA antagonists) but they can swing the balance in DA activity sufficiently to produce akinesia (Parkinsonism). DA agonists (and levodopa) may overcome akinesia but can induce DA overactivity and dyskinesia (peak dose effect) (see Chapter 15)...

Since D2 (but not Di) receptors are expressed on neurons of the Ind Path, then D2 agonists will have the same effect on this pathway as levodopa and overcome the hypokinesia. Their inability to activate D] receptors could mean, however, that while they are less likely to cause dyskinesias, for the reasons given above, their ability to dampen the GPint may also not be sufficient to give the required facilitation of motor function. Conversely, the absence of Dj receptors on the Ind Path explains why their agonists carmot influence it and so appear unable to reduce hypokinesia. 

Most cases of AzD show cerebrovascular amyloid deposits and the amyloid protein of senile plaques is the same as that found in blood vessels. It is referred to as )S-amyloid protein and is part of a 695, 751 or 770 amino-acid amyloid precursor protein APP, which is a transmembrane protein and although its precise function is not clear, it is widely distributed and APP knock-out mice show reduced motor function. Normally so-called short 40 amino-acid-soluble derivatives of APP are produced by proteolytic cleavage of APP within the j] (A4) amino-acid sequence but APP can also be cleaved... 

Echeverria D, Woods JS, Heyer NJ, Rohhnan DS, Farin FM, Bittner Jr AC, Li T, Garabedian C. 2005. Chronic low-level mercury exposure, BDNF polymorphism, and associations with cognitive and motor function. Neurotoxicol Teratol 27 781-796. 

Motor function (arm) a. Left b. Right 0 = no drift 1 = drift before 5 s 2 = falls before 10 s 3 = no effort against gravity 4 = no movement... 

Motor function (leg) a. Left 0 = no drift 1 = drift before 5 s... 

Upon admission and control of seizure activity, a neurologic exam should be conducted to evaluate level of consciousness (coma, lethargy, and somnolence), motor function and reflexes (rhythmic contractions, rigidity, spasms, and posturing), and pupillary response. A physical exam to identify secondary injuries from the SE should also be conducted. 

Levodopa, a dopamine precursor, is the most effective agent for PD. Patients experience a 40% to 50% improvement in motor function. It is absorbed in the small intestine and peaks in the plasma in 30 to 120 minutes. A stomach with excess acid, food, or anticholinergic medications will delay gastric emptying time and decrease the amount of levodopa absorbed. Antacids decrease stomach acidity and improve levodopa absorption. Levodopa requires active transport by a large, neutral amino acid transporter protein from the small intestine into the plasma and from the plasma across the blood-brain barrier into the brain (Fig. 29-2). Levodopa competes with other amino acids, such as those contained in food, for this transport mechanism. Thus, in advanced disease, adjusting the timing of protein-rich meals in relationship to levodopa doses may be helpful. Levodopa also binds to iron supplements and administration of these should be spaced by at least 2 hours from the levodopa dose.1,8,16,25... 

Silent" brain lesions on magnetic resonance imaging are associated with poor cognitive and fine motor functions pseudotumor cerebri (case report)... 

Frequent assessment of symptoms (i.e., mental status and sensory and motor function) every 4 hours until symptoms improve and then daily. 

B. J. Baum and L. Bodner, Aging and oral motor function Evidence for altered performance among older persons, J. Dent. Res., 62, 2 (1983). 

Tvedt B, Edland A, Skyberg K, et al. 1991a. Delayed neuropsychiatric sequelae after acute hydrogen sulfide poisoning Affection of motor function, memory, vision and hearing. Acta Neurol Scand 84 348-351. 

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