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Anaesthetic considerations in idiopathic orthostatic hypotension and the Shy-Drager syndrome.

Orthostatic hypotension due to autonomic failure may occur secondary to systemic disease states (notably diabetes) or as a disease entity in its own right with a variable degree of neurological involvement that has resulted in a confused classification. The diagnosis, classification and treatment of these latter forms of orthostatic hypotension is reviewed. The pathology is in the central and efferent autonomic pathway, resulting in a disordered baro-receptor reflex, postural hypotension, abnormal responses to tilting and the Valsalva manoeuvre, an inappropriately fixed heart rate and other autonomic features. Anaesthesia may be associated with profound hypotension and some of the signs of anaesthesia may be absent. The response to cardiac depressant drugs and reduction of circulating blood volume may be exaggerated due to absence of compensatory mechanisms. The response to vasoactive agents is unpredictable. The importance of preoperative evaluation, monitoring during operation and the careful selection of anaesthetic agents and techniques is discussed.

Adult↗

Development of dopaminergic neurons in the mammalian brain.

Dopaminergic neurons in the mammalian brain have received substantial attention in the past given their fundamental role in several body functions and behaviours. The largest dopaminergic population is found in two nuclei of the ventral midbrain. Cells of the substantia nigra pars compacta are involved in the control of voluntary movements and postural reflexes, and their degeneration in the adult brain leads to Parkinson's disease. Cells of the ventral tegmental area modulate rewarding and cognitive behaviours, and their dysfunction is involved in the pathogenesis of addictive disorders and schizophrenia. Because of their clinical relevance, the embryonic development and maintenance of the midbrain dopaminergic cell groups in the adult have been intensively studied in recent years. In the present review, we provide an overview of the mechanisms and factors involved in the development of dopaminergic neurons in the mammalian brain, with a special emphasis on the midbrain dopaminergic population.

Amiodarone↗

Ground reaction forces in locomoting hemi-parkinsonian rats: a definitive test for impairments and compensations.

Hemi-parkinsonian rats have preserved postural reflexes but are impaired in initiation of voluntary movements. Surprisingly, these rats can walk and run, suggesting that they can access some compensatory strategy to overcome the rigidity in their impaired limbs. The purpose of the present experiment was to investigate the locomotor compensations made by hemi-parkinsonian rats by measuring the forces exerted by the limbs on the ground throughout the stride during trotting. Rats with unilateral dopamine depletion produced by injection of 6-hydroxydopamine into the nigrostriatal bundle were trained to run back and forth in an alley for food reinforcement. Ground reaction forces were measured in three orthogonal directions using a force plate embedded in the runway. Rats were also videotaped so that limb movements were synchronized with force recordings. Although locomotion was obviously impaired, the affected limbs could support weight and provide some braking forces. In addition, the impaired hindlimb provided significant propulsive force, and a relatively large laterally directed force. Analysis of vertical movement of the centre of mass suggested that the impaired hindlimb was being used partly as a spring. The most significant abnormalities were seen during the diagonal couplet of the impaired forelimb and the unimpaired hindlimb, partly reflecting the important compensatory role of the unimpaired hindlimb. These results demonstrate that this method is useful in the analysis of hemi-parkinsonian gait and provide insights as to how rats can use an impaired limb to produce weight support and propulsion.

Adaptation, Physiological↗

Voice analysis and videolaryngostroboscopy in patients with Parkinson's disease.

Parkinson's disease (PD) is clinically characterized by a resting tremor, bradykinesia, cogwheel phenomenon, rigidity, disorder of postural reflexes and especially changes in voice and speech. We studied 30 PD patients who were treated with dopamine and 20 normal subjects as the control group. The parameters of vocal fold edges, glottal closure, vertical levels of cords, amplitude of vibration, mucosal wave, vibratory behavior, phase symmetry, ventricular folds and movements, periodicity, arytenoids and thick mucous were evaluated by videolaryngostroboscopy. The Unified Parkinson's Disease Rating Scale was applied to the patient group. The voices of the patients were evaluated by the Dr.Speech-4 and Spectra-PRO computer programs. Maximum phonation time, fundamental frequency, amplitude and the harmonic-to-noise ratio were recorded and compared with those of the control group. The abnormal videolaryngostroboscopic findings were more frequent in the PD group (70% versus 45%; P<0.05). Voice analysis showed significant differences in the parameters such as maximum phonation time, maximum fundamental frequency, the frequency range and the harmonic-to-noise ratio. We thought that these methods and parameters yielded sufficient information for diagnosis and follow-up of vocal function in patients with PD.

Female↗

Hypertension in the elderly.

The incidence of hypertension in the geriatric population is very high and is a significant determinant of cardiovascular risk in this group. The tendency for blood pressure to increase with age in westernized societies such as the United States may depend on environmental factors such as diet, stress, and inactivity. Our population tends to become more obese; to consume relatively greater amounts of sodium and lesser amounts of potassium, calcium, and magnesium; and to decrease exercising with increasing age. Senescent changes in the cardiovascular system leading to decreased vascular compliance and decreased baroreceptor sensitivity contribute not only to rising blood pressure but also to an impairment of postural reflexes and orthostatic hypotension. The hallmark of hypertension in the elderly is increased vascular resistance. Greater vascular reactivity in the elderly hypertensive patients may reflect decreased membrane sodium pump activity and decreased beta-adrenergic receptor activity as well as age-related structural changes. Treatment of diastolic hypertension in the elderly is associated with decreased cardiovascular morbidity and mortality. Although treatment of systolic hypertension may not decrease immediate cardiovascular mortality, it appears to decrease the incidence of stroke. The initial therapeutic approach to the elderly hypertensive patient should generally consist of a reduction in salt and caloric intake and an increase in aerobic exercise, i.e., walking. Drug therapy should be initiated with lower doses of medication with a special concern about orthostatic hypotension.

Age Factors↗

Consequences of damage to the sensorimotor cortex in neonatal and adult cats. I. Sparing and recovery of function.

Postural reflexes and locomotion were studied in order to assess the effects of unilateral sensorimotor cortical ablations in neonatal (1 day old) and adult cats. To document the infant lesion effect and to distinguish recovery from sparing of function, development of motor function was studied in neonatal operates and in normal littermates. Once neonatal operates achieved maturity, their motor performance was compared with that of chronic adult operates. The emergence of motor behavior during development in neonatal operates appeared to follow the same pattern as in normal animals although with a protracted time course and motor behavior did not attain the level of maturity of normal animals. Some deficits were not apparent immediately but evolved with time. Adult operates exhibited recovery of function of some behavior but neonatal operates exhibited greater recovery and sparing. Adult operates, like neonatal operates, were able to mask certain deficits by compensatory mechanisms. Kinematic analysis revealed that neonatal and adult operates often executed movements abnormally. It is hypothesized that somewhat different mechanisms underlie recovery in neonatal and adult operated animals.

Age Factors↗

Thalamus as a relay station for catalepsy and rigidity.

The aim of the study was to determine to what extent catalepsy and tonic rigidity of muscles induced by muscimol administration into the ventral thalamic nuclei disturb the motor activity of rats. This study also aimed to test whether the ventromedial thalamic nucleus (Vm) was involved in transmitting effects evoked by the systemic injection of neuroleptics or opioids. For this purpose muscimol and/or picrotoxin was injected into the ventral thalamic nuclei and the behaviour of the animals was assessed in a series of test situations. It was found that muscimol administration to the Vm disturbs not only the initiation and performance of voluntary movements but also the occurrence of avoidance when the animal's life is endangered. Postural reflexes remained, however, undisturbed. Those effects seemed to be GABA- and site-specific to Vm. The haloperidol catalepsy was strongly inhibited by administration of picrotoxin to the Vm while the morphine catalepsy remained unchanged after picrotoxin. The Vm plays a crucial role in the motor behaviour and transmission of cataleptogenic effects of haloperidol, whereas similar effects produced by morphine appear to by-pass the investigated thalamic region.

Animals↗

Neurological assessment.

Neurological assessment of certain movement disorders is described with emphasis on Parkinson's disease. In addition, abnormal behavior and changes in affect are given. Changes in neurological status, i.e., Bradykinesia, rigidity, gait changes, hand-writing irregularity, postural reflexes are outlined. The differential diagnosis of the disease is also indicated in addition to prognosis and to the biochemical correlates of Parkinson's disease.

Diagnosis, Differential↗

The influence of aging on recovery following ischemic brain damage.

Stroke is a health hazard that affects all age groups, however the impact of age on brain injury following ischemia remains largely unexamined. We examined the extent to which age, from the newborn to mature adult, affects behavioral recovery following similar degrees of ischemic brain damage. We utilized a model that produces comparable volumes of brain damage between the different ages. Endothelin-1, a potent vasoconstrictor, was injected into the brain of 10, 63 and 180-day-old rats, at the level of the right middle cerebral artery. On days 3, 7, 14, 28 and 56 post-insult, behavioral tests including rota-rod, foot-fault, open-field, inclined screen, tape-removal test and postural reflex were performed. Control animals underwent sham surgery, but ischemia was not induced. Neuropathology was assessed on day 63 post-insult. Volume of damage was determined for each brain as a percentage of the contralateral hemisphere (which remains undamaged). Our results indicated that the volume of damage for each age group was 22.97, 19.97, and 18.85% for 10, 63 and 180-day-old rats, respectively, and were not significantly different from each other. Overall, ischemic animals did significantly more poorly on behavioral testing than did controls. When broken down by age, the difference between ischemics and controls was only evident in the 63 and 180-day-old animals. The tape-removal test revealed main effects of age, group, and day (p<0.001). In addition, significant interactions were noted for day of testing by age (p<0.001), day of testing by group with ischemics performing more slowly than controls, and an age by group interaction which indicated that the 63 and 180-day-old ischemic rats did not recover completely during the testing period and remained significantly slower than their controls (p<0.001). In the foot-fault task, the 63 and 180-day-old ischemic animals performed significantly more poorly on days 3, 7, and 14 of recovery, returning to control values by day 28. The 180-day olds performed more poorly on day 3 of recovery, but then returned to control values. For open-field testing, the results indicate an overall difference between ischemics and controls, with the 63 and 180-day-old animals improving with time though they did not achieve control values. In conclusion our data suggest functional performance is poorly and inconsistently correlated with the extent of morphologic injury across all age groups. The immature rat clearly recovers more completely and more rapidly than do older, more mature rats. The findings may imply a greater degree of brain plasticity in the infant rat compared to the adult, and have important implications related to the underlying mechanisms of recovery and the association between brain damage and functional improvement.

Age Factors↗

Nursing care of patients with Parkinson's disease.

Nursing interventions for each of the symptoms of Parkinson's disease, muscle rigidity, bradykinesia, tremors at rest and postural reflex abnormalities, are designed to increase the patient's quality of life by minimizing symptoms. Nurses are responsible for planning patient medication schedules to maximize drug effectiveness. Dietary implications include a low-protein regimen for the patient during the day, eliminating foods high in Vitamin B6, high caloric foods, and soft-solid foods offered at frequent feedings. Constipation is addressed by increasing the patient's fiber and fluid intake and by increasing the patient's mobility. Patient mobility is increased when the patient is taught purposeful activities and to concentrate on the way he walks. Communication is facilitated if the patient takes deep breaths before speaking and uses diaphragmatic speech. A telephone receiver which amplifies the patient's voice is also available. Interventions are good only if the patient chooses to implement them; he is the head of the health team planning his care.

Humans↗

Non-invasive intranasal insulin-like growth factor-I reduces infarct volume and improves neurologic function in rats following middle cerebral artery occlusion.

Insulin-like growth factor-I (IGF-I) has been proposed as a treatment for stroke. However, it does not efficiently cross the blood-brain barrier (BBB). Intracerebroventricular injection of IGF-I has been shown to offer protection against cerebral ischemic damage in rats although this invasive method of administration may not be practical in humans. Non-invasive intranasal (IN) delivery of IGF-I to the brain is a promising alternative. We have assessed the therapeutic effect of IN IGF-I in rats following middle cerebral artery occlusion (MCAO). Treatment was initiated 10 min after the onset of MCAO and then again 24 and 48 h later. Intranasal dosing of 75 microg IGF-1 (225 microg total IGF-I over 48 h) significantly reduced corrected infarct volumes by 60% vs. control (P<0.01) and hemispheric swelling by 45.6% vs. control (P<0.05). Neurologic function, assessed by the postural reflex, flexor response and adhesive tape tests, was also improved by IN IGF-I as compared to control. Our study indicates IN delivery of IGF-1 holds significant promise as a non-invasive and efficacious method of bypassing the BBB for the treatment of stroke.

Administration, Intranasal↗

Damage to the vestibular inner ear causes long-term changes in neuronal nitric oxide synthase expression in the rat hippocampus.

The vestibular inner ear detects head acceleration and initiates compensatory eye movement and postural reflexes that help keep the visual image of the world stable on the retina, and maintain balance, during unexpected head movement. The most primitive vestibular systems are estimated to have evolved more than 500 million years ago and in mammalian and submammalian species the vestibular reflexes are mediated by basic brainstem pathways (see Wilson and Melvill Jones, 1979 for review). Although the contributions of the vestibular system to higher cognitive function have generally received less attention than its reflexive roles, vestibular sensory information is transmitted to higher centres in the brain and humans with vestibular damage are known to experience debilitating perceptual illusions (see Curthoys and Halmagyi, 1995; Berthoz, 1996 for reviews). Increasing behavioural and neurophysiological evidence suggests that the hippocampus uses information from the vestibular inner ear in order to build up maps of space that can be used in the development of spatial memory during learning tasks (McNaughton et al., 1991; Chapuis et al., 1992; Wiener and Berthoz, 1993; O'Mara et al., 1994; Wiener et al., 1995; Gavrilov et al., 1995; Stackman and Taube, 1996; Vitte et al., 1996; Taube et al., 1996; Save et al., 1998; Peruch et al., 1999; Cuthbert et al., 2000; Russell et al., 2000). However, to date, there has been no indication of the long-term neurochemical effects of the loss of vestibular input on hippocampal function. Since nitric oxide has been implicated in the mechanisms of hippocampal synaptic plasticity associated with the development of short-term memory (e.g. Schuman and Madison, 1991; Schuman et al., 1994; Arancio et al., 1996; Wu et al., 1997; Lu et al., 1999), we examined whether changes occur in the activity and expression of the enzymes responsible for nitric oxide production (nitric oxide synthases) in subregions of the rat hippocampus at different times following unilateral peripheral vestibular lesions, using western blotting and radioenzymatic assays. We found a decreased expression of neuronal nitric oxide synthase in the ipsilateral dentate gyrus at 2 weeks following the vestibular damage and not before, that may be related to the long-term effects of the loss of vestibular input on hippocampal function. These results support the hypothesis that head movement and position information derived from the vestibular inner ear may be important for the normal function of the hippocampus.

Afferent Pathways↗

Pathophysiology of osteoporosis.

As with many chronic diseases that express themselves late in life, osteoporosis is distinctly multifactorial, both in etiology and pathophysiology. Osteoporotic fractures occur because of a combination of injury and intrinsic bony fragility. Injury comes most often from a combination of falls, falling to the side, poor postural reflexes that fail to protect bony parts from impact, and reduced soft-tissue padding over bony prominences. The bony fragility itself is a composite of geometry, low mass density, severance of microarchitectural connections in trabecular structures, and altered bone material quality. The latter is primarily the result of accumulated fatigue damage, but reduced collagen cross-links and other intrinsic material defects may play a role as well. Reduced bone mass, in turn, is the result of varying combinations of gonadal hormone deficiency, inadequate intakes of calcium and vitamin D, decreased physical activity, comorbidity, and the effects of drugs used to treat various unrelated medical conditions. Finally, the often poor outcome from hip fracture in the elderly is partly due to associated protein-calorie malnutrition. An adequate preventive program for osteoporotic fracture must address as many of these factors as possible and be as multifaceted as the disease is multifactorial.

Accidental Falls↗

Parkinson's disease--levodopa complications.

Parkinson's disease is a readily recognized clinical syndrome, characterized by resting tremor, rigidity, bradykinesia and loss of postural reflexes. The introduction of levodopa transformed our management of this disease. As our experience has increased the long term side effects of levodopa have become more apparent. Levodopa complications comprise: wearing off, motor fluctuations, and psychiatric complications. The complexity of these clinical phenomena has been worked out with time and is now well-recognized. A number of management strategies can ameliorate these long-term complications. This article reviews the current management of late-stage Parkinson's disease.

Antiparkinson Agents↗

Memory impairment in Parkinson's disease.

A total of 52 patients with Parkinson's disease (PD), 11 with presumptive Alzheimer's disease (AD), and 20 healthy subjects were studied; subjects were aged 55-74 years. Neurological symptoms were assessed quantitatively, and the state of higher mental processes were evaluated using the Luriya method. A number of memory tests were also used. These studies showed that PD was almost always accompanied by memory impairment exceeding the age norm. The major mechanism for memory impairment in PD without dementia was inadequate independent organization of memory-related activity at the memorizing and retrieval stages. In PD with dementia, there was also a primary impairment. Differences in memory impairments were found in PD with dementia (deeper derangements of involuntary memory and of information processing during memorizing). Impairments of consolidation of traces were more dependent on the age at onset of PD, while inadequacy of independent organization of memory-related activity was more dependent on disease duration. Most memory parameters in PD correlated with the severity of disturbances in gait and postural reflexes. It is suggested that memory impairment in PD is a manifestation of the major pathological process, which shows a number of differences from other neurogeriatric diseases.

Adult↗

Benzodiazepine-induced motor impairment linked to point mutation in cerebellar GABAA receptor.

The selectively outbred alcohol-non-tolerant (ANT) rat line is highly susceptible to impairment of postural reflexes by benzodiazepine agonists such as diazepam. ANT cerebella are generally devoid of diazepam-insensitive high-affinity binding of the benzodiazepine [3H]Ro15-4513, whereas in non-selected strains such binding marks a granule-cell-specific GABAA (gamma-aminobutyric acid) receptor containing the alpha 6 subunit. A critical determinant for diazepam insensitivity of this 'wild-type' cerebellar GABAA receptor is an arginine residue in alpha 6 position 100, where other alpha subunits carry a histidine. Here we report that the alpha 6 gene of ANT rats is expressed at wild-type levels but carries a point mutation generating an arginine-to-glutamine substitution at position 100. In consequence, alpha 6(Q100)beta 2 gamma 2 receptors show diazepam-mediated potentiation of GABA-activated currents and diazepam-sensitive binding of [3H]Ro15-4513. Our results suggest that cerebellar motor control may be a distinct behavioural correlate of the alpha 6-subunit-containing GABAA receptor subtype.

Affinity Labels↗

The 'rotational preconstraint'.

This model provides a novel view of the etiology of some scolioses and can answer some of the biomechanical questions regarding pathogenesis of dorsal curves. According to our findings, paravertebral muscular imbalance is likely to favour such a pathological condition which, with the interference of the postural reflexes and the body weight-related vertical loading, might lead to the formation of a true scoliotic curve. Review of earlier research studies in the light of our findings reveals controversy in some authors' reported results and their own interpretations and seems to generally support our theory.

Humans↗