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Speech and voice abnormalities are common in individuals with Parkinson's disease (PD; Ho, Iansek, Marigliani, Bradshaw, & Gates, 1998; Logemann, Fisher, Boshes, & Blonsky, 1978), with voice frequently affected in [...], Purpose: This study investigated the impact of lexical characteristics on the intelligibility of speakers with Parkinson's disease (PD). Intelligibility was compared for listening in a quiet versus a noisy environment. Method: A total of 192 young listeners participated in the study, with 96 listeners listening in quiet and 96 listening in noise in which the spoken sentences were mixed with 10-talker babble. The listeners transcribed spoken sentences with target words controlled for word frequency and neighborhood density. The sentences were produced by 12 speakers with Pd and 12 healthy control (HC) speakers. Transcription accuracy was compared across lexical categories between PD and HC and between the two listening conditions. Results: Transcription accuracy was higher for high-frequency words than low-frequency words for both speaker groups in quiet and in noise. The neighborhood density effect was evident only in the noise condition with better intelligibility for words from sparse neighborhoods than from dense neighborhoods. Regardless of listening condition, the PD group was less intelligible with a significant decrease in intelligibility in noise relative to quiet. Conclusions: The lexical properties of the words affected listeners' understanding of Parkinsonian speech. Frequent words in sparse neighborhood enhanced intelligibility, especially under adverse listening conditions. Babble noise had a detrimental impact on the intelligibility of Parkinsonian speech. The extent of the lexical effect on intelligibility increased in noise.

Byline: E. G. Antonen (1), A. Yu. Meigal (1), Yu. V. Lupandin (1) Abstract: The authors studied muscle fatigue in patients with parkinsonism receiving pathogenetic therapy and in elderly healthy subjects by means of turn-amplitude analysis of surface electromyography (EMG). The healthy subjects reacted to fatigue with a significant increase in the amplitude and number of EMG turns during static exercise and a decrease in the peak ratio. In patients with parkinsonism, fatigue began after an exercise that was half of that in the healthy subjects with a decrease in the number of turns and mean amplitude and an increase in peak ratio. These data show that dynamics of strength and EMG parameters differs in patients with parkinsonism and healthy subjects. Author Affiliation: (1) Petrozavodsk State University, Petrozavodsk, Karelia, Russia Article History: Registration Date: 12/10/2004

Byline: N. Giladi (1), T. Gurevich (1), H. Shabtai (1), D. Paleacu (1), E.S. Simon (1) Keywords: Key words Gait; Freezing; Freezing of gait; Parkinsonism; Botulinum toxin Abstract: Background Freezing of gait (FOG) is a common and very disabling parkinsonian symptom, which is poorly understood and responds unsatisfactorily to medical treatment. We recently reported a unique patient with Parkinson's disease (PD) who had significant alleviation of FOG shortly after she was injected with botulinum toxin type A (BTX-A) for foot dystonia (Giladi et al. 1997). Objective To assess the effect of BTX-A injections into the calf muscles of parkinsonian patients on FOG. Method BTX-A was injected in an open fashion into the calf muscles of 10 parkinsonian patients (age 55--75 years) with FOG as a predominant symptom. Response of FOG was assessed subjectively by the patient from worsening (--1) to marked improvement (+3). One patient was injected in a single blind fashion with saline or BTX-A after he had an initial good response. Results Seven patients reported different rates of improvement of FOG severity in 15 out of 17 therapeutic sessions. Four patients (40%) reported marked improvement (+3) of FOG in 5 sessions. Two patients reported no effect in two sessions. The mean duration of improvement was 6 weeks (range 1--12 weeks) with definite deterioration afterwards. The patient who was injected in a single blind fashion did not respond to saline injections but improved significantly with BTX-A treatment. Conclusions We observed a clear temporal relationship between BTX-A injections into the calf muscles of parkinsonian patients and improvement of FOG. A double blind placebo controlled prospective study is needed before any conclusions can be drawn about the role of BTX-A injection in FOG. Author Affiliation: (1) Movement Disorders Unit, Department of Neurology, Tel-Aviv Sourasky Medical Center, 6 Weitzman Street, Tel-Aviv Israel 64239 Tel.: 972-3-6974912 Fax: 972-3-6974911 e-mail: ngiladi@tasmc.health.gov.il, IL Article note: Received: 31 August 2000 / Received in revised form: 24 October 2000 / Accepted: 19 January 2001

Research shows that the unfolded putative G protein-coupled transmembrane polypeptide, Pael receptor, serves as a substrate of Parkin involved in the autosomal recessive juvenile Parkinsonism (AR-JP). Results demonstrate that accumulation of the insoluble form of Pael receptor and/or Parkin leads to neuronal death in AR-JP.

Patients with Parkinson's disease (PD) often develop cognitive deficits, which often progress to dementia. The exact nature of this mental decline remains controversial. Some researchers believe that dementia in a Parkinson's patient may indicate coexisting Alzheimer's disease (AD) rather than a complication of PD. This suggestion has gained support by the finding that patients with AD or PD may develop loss of brain cells in the region of the basal forebrain, specifically the nucleus basalis of Meynert. This small cluster of neurons supplies acetylcholine input to the cerebral cortex. While the degeneration of cholinergic systems in the brain is related to the loss in intellectual function in AD patients, it has also been found that there are abnormalities of cholinergic binding by circulating lymphocytes in the blood as well. This observation indicates that the abnormalities of Alzheimer's disease extend beyond the boundaries of the nervous system. To determine if similar pathological events occur in Parkinson's disease, researchers measured the cholinergic binding of lymphocytes in 44 PD patients and in 23 age-matched volunteers. (In general, cholinergic binding is measured with pharmacologic agents, not with acetylcholine itself; in this case radioactive quinuclidinyl benzilate was used.) Twenty-four of the PD patients had no signs of dementia; the cholinergic binding was normal in 12 patients and low in six patients. (The remaining six patients had high values possibly related to medication they were receiving.) The remaining 20 PD patients all had indications of dementia; the cholinergic binding was abnormally low in all 20 subjects. These results indicate that the cholinergic binding of lymphocytes is low in patients with Parkinson's disease and dementia, similar to what is found in patients with Alzheimer's disease. (Consumer Summary produced by Reliance Medical Information, Inc.)

It is quite common to test patients being evaluated for neurological disorders with tests using words and pictures. Curiously, however, difficulties identifying odors are among the earliest signs of abnormality in some neurological diseases. The ability to identify odors was tested in 24 patients with Parkinson's disease, 24 patients with early-stage Alzheimer's disease, and 24 patients with the parkinsonism-dementia complex neurological disorder which is peculiar to Guam and some other islands in the western Pacific. The results were compared with odor identification by patients with progressive supranuclear palsy or MPTP poisoning. The results of the tests indicated that the patients with Parkinson's disease, Alzheimer's disease, and the parkinsonism-dementia complex of Guam were virtually indistinguishable in their odor-identification abilities. Similar deficits were not observed in the patients with progressive supranuclear palsy or MPTP poisoning. Since MPTP poisoning kills neurons (nerve cells) in the substantia nigra of the brain and produces motor symptoms indistinguishable from those of Parkinson's disease, the absence of the smell abnormality in these patients indicates that some other defect must be at work in the patients with actual Parkinson's disease. Three competing hypotheses have been proposed to explain the presence of the odor identification abnormalities. One is that whatever causes these diseases enters through the nose and harms the olfactory apparatus in the process; this may be plausible since many poisons and viruses can enter the brain through the nasal passages. A second hypothesis is that damage which affects the sense of smell also harms the tissues which protect the brain and render it more susceptible to factors other than those which caused the defect in odor identification. The third hypothesis is that the abnormalities in the nerve cells themselves which are characteristic of these neurological diseases directly alter the sense of smell. (Consumer Summary produced by Reliance Medical Information, Inc.)

While the cause of Parkinson's disease is not known, the data seem to indicate that some environmental factor is the cause. However, it may be that some individuals are more susceptible to the effects of this environmental cause than others. One way that such increased vulnerability might work involves alterations in liver enzymes. The liver takes on much of the task of metabolically detoxifying various potentially dangerous substances that enter the body through the digestive tract. If some liver enzymes are deficient, then more of these potentially harmful substances might be free to damage the brain and other organs. However, investigation of the liver enzymes of patients with Parkinson's disease has failed to identify any enzyme that is consistently affected. Yet several studies have found that if only patients who developed Parkinson's disease at a young age are considered, then a different pattern emerges. Whereas the liver enzyme activities of the Parkinson's patients were not significantly different from normal overall, the patients who were younger at disease onset were found to be deficient in the metabolism of the drug debrisoquine, which indicates an abnormality in the enzyme P450 IID6, part of the so-called P450 system. This suggests that different subsets of patients with Parkinson's disease might have different enzyme abnormalities. One possibility is that Parkinson's disease only develops when a person with a specific deficit happens to come into contact with some environmental substance which complements the defect. According to this view, the same environmental toxin will be irrelevant to some other Parkinson's patient who has a different enzyme defect and who comes into contact with a different toxin complementary for his particular defect. (Consumer Summary produced by Reliance Medical Information, Inc.)

The symptoms of Parkinson's disease are thought to arise from the progressive loss of dopaminergic neurons in the substantia nigra (part of the brain). Nerve fibers projecting from the substantia nigra account for the majority of dopamine found in the striatum, which consists of the caudate nucleus and the putamen. Marked impairment of the nigrostriatal pathway is seen in Parkinson's patients at postmortem study, but little is known about the function of this system during life, nor is it known precisely how deficiencies of this system contribute to the symptoms seen in Parkinson's disease. Positron emission tomography provides a method for peering into the biochemical workings of the human brain within living Parkinson's disease patients as well as healthy volunteers, and this technology was used to elucidate the pathological changes within the dopaminergic systems of patients with Parkinson's disease. Nine patients with Parkinson's disease and seven matched control subjects were examined after injection with two radioactively labelled tracers, fluorodopa and nomifensine. Fluorodopa is an analogue of levodopa, and its distribution in the brain reflects the distribution of that drug. Nomifensine, on the other hand, is taken up by the same receptors which take up dopamine and norepinephrine, and thus labels the synaptic endings of dopaminergic systems. While the overall uptake of these compounds was reduced among the Parkinson's patients, the total activity in the putamen was still 40 percent of normal, indicating that substantial dopamine activity still remains in these patients. This is in contrast to postmortem findings, in which dopamine depletion is generally extreme. When left-right differences were examined in the Parkinson's patients, it was found that left-right differences in the putamen correlated with left-right differences in disease symptoms, while left-right differences in the caudate nucleus did not. (Consumer Summary produced by Reliance Medical Information, Inc.)

Hemiparkinsonism-hemiatrophy syndrome is parkinsonian symptoms limited to half the body, with atrophy on the same side of the body or brain atrophy on the opposite side. This rare condition generally begins earlier in life than most forms of parkinsonism. While the syndrome was defined on the basis of purely clinical symptoms, the advent of modern imaging techniques has provided new insights into the pathological picture of hemiparkinsonism-hemiatrophy syndrome. The authors reviewed 11 cases of hemiparkinsonism-hemiatrophy syndrome in 2 women and 9 men. The average age of onset of the syndrome in these patients was 38.1 years; there was no family history of parkinsonism among these patients and only two patients had any history of head trauma. Six of the patients had body hemiatrophy and contralateral (opposite side) brain atrophy, four had only body hemiatrophy, and one patient had only brain hemiatrophy in addition to the hemiparkinsonism. In seven patients the affected side was the dominant side and in four the affected side was nondominant. No correlation could be found between the degrees of brain hemiatrophy and body hemiatrophy. Five of the patients developed bilateral disease as their condition progressed. This observation, which has been made in previous reports of hemiparkinsonism, suggests that both sides of the brain may be affected, but one side has a considerable head start in degenerating. One common hypothesis of the etiology of hemiparkinsonism-hemiatrophy is that the condition arises from perinatal asphyxia (insufficient oxygenation in the period shortly before to shortly after birth). It is not easy, however, to explain the long delay between the initial brain insult and the development of symptoms. One possibility, however, is that the perinatal insult carries the brain close to the edge of parkinsonian symptoms. It is known that significant destruction of neurons in the substantia nigra must take place before parkinsonian symptoms appear. If the perinatal insult comes close to the threshold, then a slight loss of neurons, which would be uneventful in a normal individual, might carry these patients over the threshold and result in neurological symptoms. (Consumer Summary produced by Reliance Medical Information, Inc.)

Visual acuity is the first thing that comes to mind when thinking of visual testing; visual acuity is the property of resolution that allows you to read, or not read, that line of tiny letters on the bottom of the wall chart. However, visual science has advanced to the point where more subtle characteristics of visual perception may be accurately measured. One of these is contrast sensitivity. Contrast sensitivity is generally measured with a target consisting of light and dark lines. Quantitatively, the light varies in a sinusoidal wave pattern as one crosses the light and dark lines; the number of waves per angle of visual field is the spatial frequency and the difference between the top and the bottom of the waves is the contrast. A temporal component, i.e. a temporal frequency, may be introduced by moving the bars across the screen at a constant speed. Eight patients with Parkinson's disease were examined for signs of visual system deficits using such spatiotemporal contrast sensitivity tests. The patients were compared with 12 healthy young controls and 7 healthy elderly controls. The results showed that there is a specific defect involving visual motion in patients with Parkinson's disease. When visual stimulus with a spatial frequency of 1 or 4 cycles per degree was moved at a frequency of 1 or 3 Hertz, the Parkinson's disease patients revealed a defect in motion sensitivity. Such a defect was not observed among the healthy elderly controls. Parkinson's disease involves dopaminergic cells in the substantia nigra, primarily affecting the striatum. It is suspected that the same defect in dopamine is responsible for the visual abnormalities observed in Parkinson's disease, but the precise pathophysiological basis is not known. (Consumer Summary produced by Reliance Medical Information, Inc.)

Dystonia (impaired muscle tone, often associated with unusual posturing of the hands or feet) is a symptom associated with several disorders of the nervous system, especially those that involve the brain regions called the basal ganglia. When the brains of patients with Parkinson's disease (PD) are examined at autopsy, many patients are found to have other degenerative nervous system diseases instead, and questions can be raised regarding the true frequency of dystonia in PD patients. To learn more regarding this issue, a search of the medical literature was performed to determine the frequency of dystonia among PD patients. In addition, dystonia in two other degenerative conditions that can be mistaken for PD, multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), was evaluated. A thorough review of the literature is presented. Dystonia is not documented in a convincing manner in many reports concerning any of the three diseases; the diagnosis was only confirmed for PD by histopathological examination in one case. PD, MSA and PSP cannot be said, on the basis of this evidence, to be associated with dystonia. Additional studies that correlate clinical and pathological evidence are necessary to ascertain the true frequency of this symptom in PD, MSA and PSP. (Consumer Summary produced by Reliance Medical Information, Inc.)

Patients with Parkinson's disease (PD), a degenerative neurologic disorder, have a variety of clinical signs and symptoms. A better understanding of the different forms that PD can take could help in its diagnosis and treatment. As part of a study about the effects of two drugs (deprenyl and tocopherol) on PD, baseline data were gathered on 800 patients with early untreated PD before they were randomly assigned to the drug testing phase. The group as a whole is referred to as the DATATOP cohort (deprenyl and tocopherol antioxidative therapy of parkinsonism). An evaluation of the spectrum of signs and symptoms among these patients is presented. Early-onset patients (whose first PD symptoms appeared at the age of 40 or younger) and late-onset patients (first symptoms at 70 or older) were disabled to the same extent, but the early-onset group had a longer duration of symptoms (2.9 years versus 1.7 years). Patients with a benign disease course (slow rate of progression) had earlier onset than those with a malignant course (fast progression). Two forms of PD were identified: the postural instability and gait difficulty (PIGD)-dominant, and the tremor-dominant, forms. Those in the former group (233 patients) had more occupational, movement, and intellectual disabilities than the 441 patients in the latter group. Family histories of PD prevalence were not different between these two groups. Follow-up of these patients is ongoing. (Consumer Summary produced by Reliance Medical Information, Inc.)

Dopamine is a catecholamine neurotransmitter produced by the brain which affects the stimulation of nerves. Alteration in the number or activity of the cell receptors that bind dopamine is thought to be involved in diseases such as Parkinson's disease and schizophrenia. Drugs that have an effect on the dopamine receptors are given to patients with these diseases. The physiological effects of dopamine occur by its binding with two types of receptors: D1 receptors, which stimulate a second enzyme known as adenylyl cyclase; and D2 receptors, which inhibit adenylyl cyclase. These receptors are G protein-coupled receptors, receptors which bind G proteins. The receptors act as a bridge, sending a message inside the cell from a signal generated by the binding of a substance such as dopamine to a receptor on the cell surface. The enzyme adenylyl cyclase stimulates the activation of the cell. The authors report that the gene encoding a dopamine D1 receptor in humans has been isolated and characterized. The D2 receptor gene had already been isolated and characterized. The protein that is encoded by the gene is similar to that of other G protein-coupled receptors, and encodes a region that spans the cell membrane seven times. When the protein that is encoded by the gene was expressed in cells, the receptor was functional. It bound dopamine and stimulated the activity of adenylyl cyclase. It is thought that other subtypes of the D1 dopamine receptor may exist. The cloning of this gene will allow for further research so that the function of this gene, and how it is activated and regulated in both normal and disease states, can be understood. (Consumer Summary produced by Reliance Medical Information, Inc.)

Dopamine is a neurotransmitter (a chemical which transmits messages between nerve cells), and it is produced by the brain. Abnormalities in the binding of dopamine to its receptors on cells are thought to occur in diseases such as schizophrenia and Parkinson's disease. Drugs that have effects on the dopamine receptors are given to patients with these diseases. The physiological effects of dopamine occur when it binds to two types of receptors: D1 receptors, which stimulate an enzyme known as adenylyl cyclase; and D2 receptors, which inhibit adenylyl cyclase. These receptors convey a message into the cell; the message is generated by the binding of a substance such as dopamine to a receptor on the cell surface. The D1 receptors mediate some behavioral responses, while D2 receptors regulate the growth and maturation of nerve cells. The gene encoding the D2 receptor has previously been isolated and characterized. The isolation and characterization of the gene encoding a dopamine D1 receptor in humans and rats is now reported. When the protein that is encoded by the gene was expressed in cells, the receptor was functional. It bound an antagonist of dopamine and stimulated the activity of adenylyl cyclase. The gene is active in various areas of the brain, especially the basal ganglia. The cloning of this gene will allow further research to be done to understand the function of this gene and how it is activated and regulated in both normal and disease states. (Consumer Summary produced by Reliance Medical Information, Inc.)

Dopamine is a neurotransmitter produced by the brain which affects the stimulation of nerves. Defective binding of dopamine to its cell receptors may be an important aspect of diseases such as Parkinson's disease and schizophrenia, and perhaps drug addiction and alcoholism. Drugs that exert effects upon the dopamine receptors are given to patients with these diseases. The receptors are classified as G protein-coupled receptors, receptors which bind G proteins. There are two types of dopamine receptors, D1 and D2. The D1 receptors regulate the growth and maturation of nerve cells, influence some behavioral responses, and modify events caused by the D2 receptors. The gene encoding a dopamine D1 receptor in humans has been isolated and characterized. It is located on chromosome 5, near two other G protein receptors. When the protein that is encoded by the gene was expressed in cells, the receptor was functional. It bound an antagonist of dopamine and stimulated the activity of the enzyme adenylyl cyclase. The gene was found to be expressed in areas of the brain such as the frontal cortex and hypothalamus. The identification of the gene and its location on chromosome 5 allows for further study to see if individuals with abnormalities of this receptor have a particular disease state. (Consumer Summary produced by Reliance Medical Information, Inc.)

Parkinson's disease may cause reduced contrast sensitivity; this visual symptom impairs the patient's perception of a boundary between a lighter and darker shade of gray, even when the patient's visual acuity is normal (that is, the patient does not require glasses for lack of visual sharpness). It remains uncertain how closely this reduced contrast sensitivity is related to the destruction of brain cells which produce dopamine, the pathological effect of Parkinson's disease thought to be responsible for the symptoms of abnormal movements. Curiously, the movement symptoms of Parkinson's disease seem to vary through the day, according to a daily rhythm which is independent of whether the patient receives medication at particular times of day. A study was undertaken to determine if similar circadian rhythms could be observed in the symptom of reduced contrast sensitivity. A total of 23 patients with Parkinson's disease were tested, as were 12 normal controls. Of the Parkinson's disease patients, the movement symptoms of 12 seemed to remain constant through the day. In the remaining 11, the movement symptoms varied with the time of day, and in nine patients the best time of day was felt to be the morning. When the tests of contrast sensitivity were performed at 8:30 AM, there were no differences between the patients and healthy control subjects. In contrast, testing later in the day revealed varying degrees of deficit among the patients. Furthermore, when the contrast sensitivity of the patients showing circadian rhythms was compared with the contrast sensitivity of the patients who did not, there were no significant differences. This observation indicates that variations in the daily cycle of abnormal contrast sensitivity may occur even when the movement symptoms of the same patient show no such circadian rhythm. The results are interpreted to suggest that, although contrast sensitivity does not involve movement at all, contrast sensitivity is nevertheless affected by the same underlying pathological process which affects the motor system. (Consumer Summary produced by Reliance Medical Information, Inc.)

Patients with Parkinson's disease (PD) commonly complain of problems with their vision. However, testing for visual acuity, the sharpness of vision which is evaluated with the common eye chart, reveals no deficit among the Parkinson's patients, and examination of the eye itself reveals no pathological changes which might be attributable to PD. But there is much more to vision than the ability to read an eye chart. A study was therefore conducted to evaluate the sensitivity of 41 patients with Parkinson's disease to visual spatial contrast. Such a test is generally conducted using an apparatus which generates grey bars on a video screen; the patient must be able to distinguish bars of varying width and varying contrast with adjacent areas. The performance of the patients was compared with the performance of 22 normal volunteers of about the same age as the Parkinson's patients. The results demonstrated that there is, indeed, a deficit in contrast sensitivity among the patients with Parkinson's disease. This deficit, however, was limited to the more severely affected patients. The nine patients with stage 2 PD had contrast sensitivity curves which were indistinguishable from normal. However, patients with more advanced disease had deficits which increased with advancing stage. The stage 4 patients were most severely affected and were different not only from the healthy controls but also from patients with less advanced disease. While this study demonstrates that patients with Parkinson's disease have a deficit in visual spatial contrast perception which increases with disease severity, it is not known whether this deficit actually contributes to the vague complaints of poor vision which are expressed by the patients. (Consumer Summary produced by Reliance Medical Information, Inc.)

Juvenile onset parkinsonism with dystonia is an uncommon inherited disorder. The syndrome consists of parkinsonian abnormalities which include tremor, rigidity, and slow movement, along with dystonia (impaired muscle tone). The disorder is believe to be inherited as a dominant gene with low penetrance, indicating that not all people who inherit the gene actually develop the disorder. The disorder responds to treatment with levodopa, and thus may be related to another group of genetic disorders, the dopa-responsive dystonias. There has been only one previous neuropathological examination of a case of juvenile onset parkinsonism with dystonia. In the present case, a six-year-old girl developed symptoms of parkinsonism which rendered her unable to walk. When the patient was 30 years of age, levodopa became available, and in response to treatment the patient again became able to walk. The improvement was not sustained, however, and the patient developed severe left-sided involuntary movements. The patient died at 39 years old of an abdominal infection. Upon autopsy, it was found that there was severe nerve cell loss in the substantia nigra of the patient's brain, similar to that seen in patients with Parkinson's disease. Many of the cells in the medial part of the substantia nigra were devoid of the black melanin pigment from which the substantia nigra gets its name. This absence of pigment is normal for a child, but abnormal for a 39-year-old woman. Pathological examination of the brain also revealed the presence of Lewy bodies. Lewy bodies are cytoplasmic inclusions, which are small structures visible within cells. While some types of cytoplasmic inclusions may be found in a variety of different disorders, Lewy bodies are rare in persons under the age of 50 in any disorder except Parkinson's disease, for which they constitute a classical pathological finding. The observation of Lewy bodies in this case suggests that hereditary early-onset parkinsonism may have similar physiological mechanisms as Parkinson's disease itself. Elucidation of the genetic mechanisms might therefore provide insight into Parkinson's disease as well. (Consumer Summary produced by Reliance Medical Information, Inc.)

Despite intensive research, the cause of Parkinson's disease remains unknown. While it is clear that much of the pathology of Parkinson's disease involves the death of nerve cells in the substantia nigra region of the brain, the pathological details of the progression of Parkinson's disease are also unknown. The authors believe that in divining the cause of a degenerative disease, a first step is the development of a conceptual model. In a detailed discussion of the progression of Parkinson's disease, the authors develop just such a model. Just as muscle and blood respond to compensate for stress or damage, nervous tissues have compensatory mechanisms as well. Evidence indicates that as some dopamine-producing cells of the substantia nigra die, the remaining cells alter their function to compensate, at least in part.The surviving neurons increase their synthesis of dopamine, which is a substance involved in the transmission of nerve signals, and increase the rate of delivery of dopamine as well. The net result is an increase in the dopamine delivery per cell of at least five-fold. Dopamine receptors may also increase in number, which would further increase the responsiveness of the system to compensate for the death of some neurons. Although there is reason to suspect that the chemical degradation that occurs after death may artificially inflate the apparent loss of dopamine in the postmortem neurochemical analysis of the brains of Parkinson's disease patients, it seems clear that a tremendous loss of dopamine-producing neurons is sustained before the disease becomes symptomatic. Animal studies indicate that roughly 80 percent of the substantia nigra neurons must die before the compensatory mechanisms are no longer adequate and disease symptoms appear. Ironically, the compensatory mechanisms themselves may cause some harm themselves and accelerate the degenerative process. The enhanced turnover of dopamine within these neurons may result in the excessive accumulation of toxic dopamine metabolic products, which may contribute to the ultimate degeneration of the surviving neurons. (Consumer Summary produced by Reliance Medical Information, Inc.)

Patients with Parkinson's disease often have abnormalities of function of the autonomic nervous system. The abnormalities include lower blood pressure when lying down and suddenly standing up, lower norepinephrine response when standing up, and reduced sensitivity to adrenalin. These observations have been made on Parkinson's patients with established disease who have, in general, been under drug therapy for their condition. As a part of the evaluation of a new drug for the treatment of Parkinson's disease, researchers evaluated the blood pressure and catecholamine responses in six patients with early-stage disease who had never undergone drug treatment. The effectiveness of the new drug, CY 238-243, has not yet been reported, but the effects of the drug on autonomic nervous system function were measured and compared in the patients and nine age-matched volunteer subjects. The researchers were unable to detect abnormalities of cardiovascular regulation in the Parkinson's patients, which suggests that the previously reported abnormalities may be a result of drug treatment or more advanced Parkinson's disease. The drug CY 208-243, which acts as an agonist of the D1 dopamine receptors in the nervous system, was found to decrease resting systolic blood pressure and to reduce the levels of circulating norepinephrine. The drug also reduced the heart rate and blunted the physiological response to standing up. The increase in blood pressure and the increase in circulating norepinephrine, which normally occur upon standing, were reduced by CY 208-243. These results indicate that D1 dopamine receptors in the brain play an important role in the normal regulation of sympathetic tone. (Consumer Summary produced by Reliance Medical Information, Inc.)

Bradykinesia, or slow movement, is a characteristic feature of patients with Parkinson's disease, but the mechanisms responsible for this slowness are far from clear. Voluntary movement is a very complicated affair; the brain must decide on the appropriate movement and a series of involuntary postural adjustments must be made before the movement is begun. For example, when lifting an object from a standing position, involuntary adjustments of the leg muscles, to compensate for the impending change of the center of gravity, begin before the arms start to lift the object. In a study of movement among 20 patients with Parkinson's disease and 20 healthy controls, researchers analyzed each stage of voluntary movement separately. The patients stood on pressure-sensing plates looking at a green light-emitting diode (LED) which served as the ''go'' signal. Electrodes were attached to muscles of the legs. The patients were instructed to stand on their tiptoes when the LED flashed green. Just prior to the onset of movement, the electrical activity of muscles quiets down, presumably because the brain is organizing the control of those muscles during that time. After the green light was observed, such a premotion silent period (PMSP) in the muscle electrical activity could be detected. After the PMSP, electrical activity was recorded reflecting the involuntary postural changes, which were ultimately followed by the actual standing on tiptoes. It was found that the onset time of the PMSP was the same for both the Parkinson's patients and the control subjects. This indicates that the mental activity necessary to perceive the light and determine the response is equally rapid in both groups. However, all the succeeding steps were slower among the Parkinson's patients. The PMSPs were longer for the Parkinson's patients, and the duration of the PMSPs correlated with the degree of clinical bradykinesia. The slowness of the voluntary movement is well established, of course, but the results of the present study also showed that the involuntary postural adjustments which precede a voluntary movement are also slow in patients with Parkinson's disease. (Consumer Summary produced by Reliance Medical Information, Inc.)