Dyskinetic Syndrome Research Articles

"Glu/GABA-Gln" metabolic loop abnormalities in iminodipropionitrile (IDPN)-induced dyskinetic syndrome.

Iminodipropionitrile (IDPN)-induced dyskinetic syndrome is characterized by abnormal repetitive involuntary movements with abnormalities in the neuro-transmission. This study explored the mechanism of glutamate (Glu)/γ-aminobutyric acid (GABA)-glutamine (Gln) metabolic circuit in rat dyskinetic syndrome and the possible regulation mechanism of "tiapride (Tia)." Male Wistar rats were assigned to the control group, dyskinetic syndrome group, and Tia group. Dyskinetic syndrome was induced by injecting with 3,3'-iminodipropionitrile for 7days. Tia group was treated with tiapride, while the control and dyskinetic syndrome groups were gavaged with saline. Eventually the Glu, GABA, and Gln concentrations in striatum were detected using UPLC-3QMS, additionally another amino acid neurotransmitters (aspartate, glycine) were also detected. Expressions of glutamine synthetase (GS), glutamate transporter (EAAT2), glutamate decarboxylase (GAD65/67), and γ-aminobutyric acid transporter protein (GAD-T) were observed using Western blot and real-time polymerase chain reaction. The behavior test scores of dyskinetic syndrome group were increased compared with the control group. Tia group decreased the behavior test scores compared with dyskinetic syndrome group. For amino acid neuro-transmission, dyskinetic syndrome group increased Glu level (p < 0.01), decreased GABA level (p < 0.01), increased Glu/GABA ratio (p < 0.01), and decreased Asp level (p < 0.01) compared with control group. Tia group decreased Glu level (p < 0.01), increased GABA level (p < 0.01), decreased Glu/GABA ratio (p < 0.01), and increased Asp level (p < 0.05) compared with dyskinetic syndrome group. For Glu/GABA-Gln circuit, the protein and mRNA expression of GS and EAAT2 in dyskinetic syndrome group were decreased (p < 0.05). Tia group increased protein and mRNA expression level of GS (p < 0.05) and EAAT2 (p < 0.01). The rat dyskinetic syndrome has Glu/GABA-Gln abnormalities. "Tiapride" upregulated the protein expression of GS and EAAT2, reduce Glu levels, increase γ-GABA levels, and eventually improve amino acid neurotransmitter imbalance.

Neuro-orthopedic deformities managment: A multidisciplinary approach

Dystonic and dyskinetic syndromes produce musculotendinous retractions, subluxations and hip or shoulder dislocations. Most of the time, deep brain stimulation and pallidotomy cannot be used in secondary syndromes as they are in primitive forms. Drug treatments have frequent side effects. Very often these treatments are inadequate to prevent musculoskeletal deformities, which have an impact on pain, nursing, positioning and quality of life. We followed a 45-year-old man with a spastic tetraparesia and a generalised dystonic and dyskinetic syndrome residual of a cerebral anoxia due to a heart arrest. His initial treatment was oral baclofen, anticholinergics and secondary intratechal baclofen. His symptoms increased progressively: pain, communication and nursing difficulties, mispositioning, elbow crease mycosis, as a consequence of musculoskeletal deformities. The patient had triple flexion of his upper limbs, antero inferior irreducible left shoulder dislocation, bilateral flessum of the knees. Multidisciplinary management has been provided, initially surgical then medical. Surgery included rotator cuff desinsertion of the left shoulder, needle percutaneous tenotomies of left elbow flexors, biceps femoris and semitendinus and plaster cast immobilisation. The medical treatment included twice-daily bolus of intratechal baclofen with dose-increase, botulinum toxin injection (left semimembranosus, right shoulder retractor muscles), phenolyc neurolysis (bilateral ansa pectoralis, left musculocutaneous nerve), physiotherapy and occupational therapy. The pain relief allowed a progressive morphinic doses decrease. Both armchair and bed positioning have been improved. Dyskinetic movements disappeared and verbal communication became easier. Neuro-orthopedic deformities management in patients with dystonia and dyskinesia may allow a decrease of dyskinetic movements and improve their comfort. It consists of multidisciplinary medicosurgical approach with tenotomies in association with oral or intratechal baclofen, botulinum toxin, chemical neurolysis and rehabilitation.

Ameliorative effect of gastrodin on 3,3′-iminodipropionitrile-induced memory impairment in rats

3,3′-Iminodipropionitrile (IDPN), one of the nitrile derivatives inducing neurotoxicity, causes the dyskinetic syndrome and cognitive impairment. Gastrodin is widely used to treat neurological disorders and showed to improve cognitive functions. The present study aimed to determine whether treatment with gastrodin can attenuate IDPN-induced impairment of memory consolidation in the passive avoidance (PA) task, and to explore the possible neural mechanisms. Our results showed that intragastric administration of gastrodin (200mg/kg) reversed the IDPN-induced impairment of memory consolidation as indicated by the prolonged retention latency in the PA task. Furthermore, gastrodin reverted IDPN-induced reduction of serotonin (5-HT) and elevation of serotonin turnover ratio. Gastrodin treatment prevented the increase of serotonin transporter (SERT) and the decrease of serotonin 1A (5-HT1A) receptor expression in the hippocampus of IDPN-treated rats. These results suggest that long-term gastrodin treatment could represent a novel pharmacological strategy for IDPN-induced memory impairment, as well that its protective effect is mediated through normalization of the serotoninergic system.

Chorea: Secondary to Non-Ketotic Hyperglycemia: A Case Report

Chorea associated with non-ketotic hyperglycaemia is an uncommon dyskinetic syndrome in uncontrolled or undiagnosed diabetes. Various theories are postulated but the underlying mechanism remains poorly understood. We report a 70-year-old man suffering from sudden choreodystonic movements and undiagnosed hyperglycemia. It always marks the importance of screening for diabetes as a cause of acute onset of hyperkinetic disorders.

Neurological syndromes associated with drug use. Frequency and characterisation

IntroductionThe need for safe health care, in which the care and treatment of the patient does not cause any injuries in addition to those already arising from their baseline disease, has led to the present study. Our objective has been to determine the frequency and describe the neurological syndromes attributable to drugs, their preventability and the levels of medical care involved. MethodsObservational study. Cohort of subjects referred from Primary and Specialised Care between December 2008 and January 2010 due to neurological symptoms attributable to drugs, and previously known neurology patients who began to have symptoms other than those of the baseline disease, also caused by drugs. The notifications were recorded in a questionnaire. Frequency distributions, central tendency measurements, χ2 or Fisher tests and non-parametric tests were performed. ResultsThe prevalence of adverse neurological events was 0.586% of the total sample. Of the 105 patients selected, the most frequent adverse events were: 25.7%, akinetic-rigid syndrome, 18.1%, dyskinetic syndrome, 11.4% neuro-psychiatric symptoms, and 10.5% confusional syndrome. The most commonly recorded pharmacological groups were, in decreasing order: anti-epileptic, dopaminergic, antidepressant, neuroleptic, antivertiginous and prokinetic drugs. We describe the most susceptible population and the statistically significant relationships between the presence of certain pharmacological groups and neurological syndromes. ConclusionsThe low prevalence detected may be due to the study design, although adverse neurological events accounted for 2.84% of the admissions to a Neurology Unit. Understanding the epidemiology should help us to identify the safest approaches, apply them correctly to the population at a higher risk, and reduce healthcare needs and consumption of medical resources.

Síndromes neurológicos asociados al uso de medicamentos. Frecuencia y caracterización

IntroductionThe need for safe health care, in which the care and treatment of the patient does not cause any injuries in addition to those already arising from their baseline disease, has led to the present study. Our objective has been to determine the frequency and describe the neurological syndromes attributable to drugs, their preventability and the levels of medical care involved. MethodsObservational study. Cohort of subjects referred from Primary and Specialized Care between December 2008 and January 2010 due to neurological symptoms attributable to drugs, and previously known neurology patients who began to have symptoms other than those of the baseline disease, also caused by drugs. The notifications were recorded in a questionnaire. Frequency distributions, central tendency measurements, X2 or Fisher tests and non-parametric tests were performed. ResultsThe prevalence of adverse neurological events was 0.586% of the total sample. Of the 105 patients selected, the most frequent adverse events were: 25.7%, akinetic-rigid syndrome, 18.1%, dyskinetic syndrome, 11.4% neuro-psychiatric symptoms, and 10.5% confusional syndrome. The most commonly recorded pharmacological groups were, in decreasing order: anti-epileptic, dopaminergic, antidepressant, neuroleptic, antivertiginous and prokinetic drugs. We describe the most susceptible population and the statistically significant relationships between the presence of certain pharmacological groups and neurological syndromes. ConclusionsThe low prevalence detected may be due to the study design, although adverse neurological events accounted for 2.84% of the admissions to a Neurology Unit. Understanding the epidemiology should help to identify the safest approaches, apply them correctly to the population at a higher risk, and reduce healthcare needs and consumption of medical resources.

Brain and Upper Extremity PET/CT Findings of Hyperglycemia-Induced Hemiballism-Hemichorea

Hyperglycemia-induced hemiballism-hemichorea is an uncommon movement disorder probably related to vascular insult of the basal ganglia in patients with poorly controlled diabetes. This rare clinical entity has been reported with abnormal brain findings on CT, MR, and F-18 FDG PET. The author presents additional PET/CT features of such an unusual dyskinetic syndrome with increased radiotracer uptake in the left motor cortex and musculature of the right shoulder girdle and upper extremity from hemiballism-hemichorea.

Acute parkinsonism with corresponding lesions in the basal ganglia after heroin abuse

Parkinsonian syndromes with encephalopathy after heroin abuse are rare. We report a 41-year-old Caucasian woman presenting with symmetric akinetic-rigidic parkinsonism. Twenty-four hours after snorting heroin, the patient exhibited a generalized dyskinetic syndrome and impaired vision, and severe parkinsonian symptoms developed within 2 weeks. The akinetic-rigid syndrome showed good …

Protective Effect of Hydrocortisone on Iminodipropionitrile‐Induced Neurotoxicity in Rats

Occupational and environmental exposure of synthetic nitriles is of potential relevance to human health. Iminodipropionitrile (IDPN), a prototype nitrile toxin, has been shown to produce dyskinetic syndrome in rodents. This study reports the effect of concomitant exposure of rats to hydrocortisone and IDPN on behavioural abnormalities namely excitation, circling and chorea (ECC) syndrome. Four groups of female Wistar rats were given hydrocortisone (0, 10, 30 and 60 mg/kg, gavage, for 10 days) 30 min. before IDPN (100 mg/kg, intraperitoneally for 8 days). Two additional groups of rats were treated with either saline (control group) or 60 mg/kg of hydrocortisone (drug alone group). The animals were observed for neurobehavioural abnormalities including dyskinetic head movement, circling, tail hanging, air righting reflex and contact inhibition of righting reflex. After behavioural studies, the animals were killed, and the discrete brain regions and temporal bones were collected for biochemistry and inner ear histopathology, respectively. Hydrocortisone significantly and dose dependently attenuated the incidence and severity of IDPN-induced behavioural syndrome. Administration of hydrocortisone (60 mg/kg) alone significantly increased glutathione (GSH) levels in olfactory bulb and striatum, whereas IDPN alone significantly reduced GSH levels in olfactory bulb, striatum and hippocampus. Hydrocortisone (60 mg/kg) significantly compensated IDPN-induced depletions of GSH in different brain regions. Hydrocortisone also protected the animals against IDPN-induced vestibular hair cell degeneration. The protective effect of hydrocortisone may be attributed to its anti-inflammatory and antioxidant properties.

Metoclopramide attenuates iminodipropionitrile-induced oxidative stress and neurobehavioral toxicity in rats

Metoclopramide (MET) has long been used as a neuroleptic and antiemetic drug in clinical practice. Motor impairment and dyskinesia have been reported in some patients following chronic treatment with MET. Occasionally, the adverse symptoms may appear even after acute exposure to MET in more susceptible population (such as elderly individual) or due to concomitant exposure to MET and certain neurotoxins. Iminodipropionitrile (IDPN), a prototype nitrile toxin, has been shown to produce dyskinetic syndrome in rodents. This study reports the effect of concomitant exposure of rats to MET and IDPN on behavioral abnormalities in rats namely excitation, circling and chorea (ECC) syndrome. Four groups of female Wistar rats (aged 3 months) were given MET (0, 10, 40 and 80 mg/kg, i.p., for 11 days) 30 min before IDPN (100 mg/kg, i.p. for 8 days). Two additional groups of rats were treated with either saline (control group) or 80 mg/kg of MET (drug alone group). The animals were observed for neurobehavioral abnormalities including dyskinetic head movement, circling, tail hanging, air righting reflex and contact inhibition of righting reflex. Horizontal and vertical locomotor activities and fore limbs grip strength were also measured. On day 12, the animals were sacrificed and brains were collected for biochemical analysis. MET significantly and dose-dependently protected the animals against IDPN-induced ECC syndrome, motor impairment and deficiency in grip strength. MET also protected the animals against IDPN-induced oxidative stress.

Influence of age on iminodipropionitrile-induced vestibular and neurobehavioral toxicities in rats

A direct association between aging and drug-induced dyskinesia has been reported by several investigators. Iminiodipropionitrile (IDPN), a prototype nitrile compound produces a motor syndrome in rodents, which resembles neuroleptic drug induced dyskinesia. In this investigation attempt has been made to study the effect of age on IDPN induced vestibular hair cell degeneration and resulting dyskinetic syndrome. Male Wistar rats aged 3, 6 and 12 weeks received IDPN in the doses of 0, 200 and 400 mg/kg, intraperitoneally for 3 consecutive days. IDPN-induced dyskinesia was assessed using a behavioral testing battery on days 3, 4, 5, 6, 7, 14, 21 and 28. The rats were sacrificed on day 28; temporal bones were excised for vestibular histopathology and sera were collected for measuring the indices of oxidative stress (glutathione and conjugated dienes). IDPN in the dose of 200 mg/kg produced dyskinesia in 12 weeks old rats, but failed to do so in 3 and 6 weeks old rats. The high dose of IDPN (400 mg/kg) caused dyskinesia in all age groups, however, its onset and severity were age-dependent. Older rats showed an early onset and significantly high incidence of dyskinesia as compared to younger rats. The susceptibility of rats to IDPN-induced behavioral deficits was proportional to oxidative stress and degeneration of sensory hair cells in the crista ampullaris.

Acute administration of haloperidol induces apoptosis of neurones in the striatum and substantia nigra in the rat

Chronic administration of typical neuroleptics is associated with tardive dyskinesia in some patients. This dyskinetic syndrome has been associated with loss of GABAergic markers in the basal ganglia but the cause of these GABAergic depletions remains uncertain. Haloperidol, a commonly prescribed typical neuroleptic, is known to be toxic in vitro, possibly as a consequence of its conversion to pyridinium-based metabolites and potentially by raising glutamate-mediated transmission. We report here that the in vivo, acute administration of a large dose of haloperidol resulted in a microglial response indicative of neuronal damage. This was accompanied by an increase in the number of apoptotic cells in the striatum (especially in the dorsomedial caudate putamen) and in the substantia nigra pars reticulata. These apoptotic cells were characterised by the stereotaxic injection of a retrograde neuroanatomical tracer into the projection targets of the striatum and substantia nigra pars reticulata prior to the systemic injection of haloperidol. This procedure confirmed that the dying cells were neurones and demonstrated that within the striatum the majority were striatopallidal neurones though relatively high levels of apoptotic striatoentopeduncular neurones were also seen. The possibility that chronic administration of haloperidol could induce cumulative neuronal loss in the substantia nigra pars reticulata and thereby induce the pathological changes which lead to tardive dyskinesia is discussed.

Nitric oxide synthase inhibitor aminoguanidine potentiates iminodipropionitrile-induced neurotoxicity in rats

This investigation was undertaken to study the effect of nitric oxide synthase inhibitor, aminoguanidine on iminodipropionitrile (IDPN)-induced neurobehavioral and vestibular toxicity in rats. The dyskinetic syndrome was produced in male Wistar rats by i.p. injections of IDPN (100 mg/kg) for 6 days. Aminoguanidine was administered orally in the doses of 50, 150 and 300 mg/kg, 60 min before IDPN in three different groups. Control rats received vehicle only, whereas another group was treated with 300 mg/kg of aminoguanidine alone (without IDPN). Our results showed that aminoguanidine significantly and dose dependently exacerbated the incidence and intensity of IDPN-induced dyskinetic head movements. Aminoguanidine potentiated IDPN-induced loss of air righting reflex. The histopathological examination of inner ear showed aggravation of IDPN-induced degeneration of sensory hair cells in the crista ampullaris by aminoguanidine. These results suggest the role of nitric oxide in IDPN-induced neurobehavioral and vestibular toxicity.

Epidemiology of nasal polyps.

Nasal polyps are found in 36% of patients with aspirin intolerance, 7% of those with asthma, 0.1% in children, and about 20% in those with cystic fibrosis. Other conditions associated with nasal polyps are Churg-Strauss Syndrome, allergic fungal sinusitis, and cilia dyskinetic syndrome, (Kartagener's) and Young Syndrome. Nasal polyps are statistically more common in nonallergic asthma versus allergic asthma (13% vs 5%, P < 0.01). About 40% of patients with surgical polypectomies have recurrences. There appears to be a hereditary factor for developing nasal polyps. A classification system for staging nasal polyps is proposed in order to standardize treatment, consider differential diagnosis, and harvest meaningful comparative research information.

Negative symptoms, cognitive dysfunction, tardive akathisia and tardive dyskinesia.

This study examined the relationship of neuropsychological deficits and negative symptoms with tardive akathisia in chronic schizophrenic patients. Consecutive volunteers (n = 100) were recruited from Community Health Centres with a DSM-III-R diagnosis of schizophrenic disorder, chronic and on stable medication. Subjects were subgrouped into tardive akathisia (TA), tardive dyskinesia (TD) and control groups using four sets of criteria. Detailed single examinations were performed using the following measures: sociodemographic, illness-related and treatment-related variables, Negative Symptom Rating Scale (NSRS), Abnormal Involuntary Movement Scale (AIMS), Rating Scale for Extrapyramidal Side-Effects (EPSE), Akathisia Rating Scale, Barnes Akathisia Rating Scale, and a brief neuropsychological test battery. Group comparisons and logistic regression analyses were performed in order to test the significance of findings. TA ratings showed a significant association with NSRS subscale scores, and with some neuropsychological test scores (Symbol Digits Modalities Test, and to a lesser extent Trail Making Test and Finger Tapping Test). TD scores showed a consistent association with age, and a less consistent association with gender, and their association with NSRS subscale scores and neuropsychological dysfunction was positive but less significant. Higher EPSE scores predicted TA and limb truncal (LT) dyskinesia. In conclusion, TA showed a more significant association with some clinical indices of organic brain dysfunction than the oral-lingual-buccal-facial dyskinetic syndrome. Prospective studies are necessary to determine whether organicity is a vulnerability factor for TA. Both our data and the published literature suggest that the movement disorder seen in TA and TD is but one feature of complex syndromes that include motor and cognitive features.

Tardive dyskinetic syndrome in rats infected with Borna disease virus

Tardive Dyskinesia (TD) is a hyperkinetic movement disorder caused by chronic treatment of psychiatric patients with dopamine (DA) receptor blocking drugs (Stacy & Jankovic 1991). Although TD is one of the most important and frequently encountered iatrogenic disorders in clinical medicine, its pathophysiology is poorly understood. We have observed a hyperkinetic movement disorder in rats experimentally infected with a neurotropic RNA virus, Borna disease virus, that may provide important insights into the pathophysiology of TD. Like TD patients, infected rats show prominent orofacial dyskinesias. In keeping with the dopamine (Goetz & Klawans 1982) and anatomic (Fibiger & Lloyd 1984) hypotheses of TD, the Borna disease rat model shows enhanced behavioural sensitivity to DA agonists and selective striatal cell damage. There is also evidence of DA deafferentation and heterogeneous reduction of D2 binding in the caudate-putamen, particularly from sites implicated in oral behaviour. These observations on a virus-induced movement disorder offer novel approaches to TD pathogenesis.

Glutaric Aciduria Type 1: First Reported Cases in Three Saudi Patients

The clinical and biochemical findings in three patients with glutaric aciduria Type 1 (GAT1) are presented. They had a normal postnatal period of three to 14 months. They developed sudden and severe encephalopathy following an infection or trauma (patient 3) that gradually progressed to severe dystonia, choreoathetosis, spastic quadriplegia and mental retardation. Neuroradiologic studies of the brain revealed white matter disease and frontotemporal lobe hypoplasia. The urine findings by gas chromatography/mass spectrometry (GC)/(MS) were characteristic of GAT1. Since GAT1 is an organic acidemia without intermittent acidotic attacks, but primarily manifests with progressive encephalopathy, it is important to recognize the potential of its existence among handicapped children in chronic care facilities. The good clinical response in two of the patients urges early diagnosis in subsequent newborn siblings of the families with the disease. The diagnosis of three patients in less than two years indicates the need for neonatal screening for the recognition of this disease, among other treatable metabolic diseases, in Saudi Arabia.

Effect of selenium and vitamin E on iminodipropionitrile induced dyskinesia in rats.

The present study was undertaken to determine the effect of combination of selenium and vitamin E on experimentally induced dyskinesia in rats. The dyskinetic syndrome was produced in 4 groups of 6 male rats each weighing 250-300g by intraperitoneal (ip) administration of iminodipropionitrile (IDPN) in doses of 100 mg/kg body weight daily for 12 days. A group of 6 rats (group 1) served as control and received normal saline only. The rats in group 2 (IDPN only) received normal saline (ip) 30 minutes before the administration of IDPN. The animals in groups 3, 4 and 5 received selenous acid (5 mumol/kg), vitamin E (500 mg/kg p.o.) and a combination of selenous acid and vitamin E respectively, daily, 30 minutes before IDPN for 12 days. Twenty four hours after the last dose of IDPN, the dyskinetic behavior including vertical head movements (retrocollis), horizontal head movements (laterocollis), circling and backwalking of each rat was studied for a period of 10 minutes. Immediately after behavioral studies, the animals were sacrificed and brains were dissected out for the analysis of conjugated dienes, lipid hydroperoxides and vitamin E. The results of this study showed that treatment of rats with IDPN only for 12 days produced dyskinetic syndrome in all the rats characterized by vertical and horizontal head movements, circling and backwalking. Concomitant treatment of rats with vitamin E and selenium individually reduced IDPN induced dyskinesia, and the symptoms were almost completely absent when the combination of these two agents was used.(ABSTRACT TRUNCATED AT 250 WORDS)

β,β′-Iminodipropionitrile-induced persistent dyskinetic syndrome in mice is transiently modified by MPTP

Chronic administration of iminodipropionitrile (IDPN) is known to produce a persistent dyskinetic syndrome. Recent neurochemical reports seem to point out the dopaminergic system as having an important role in mediating IDPN syndrome. In order to identify a possible role for the nigrostriatal dopaminergic pathway in determining at least some aspects of the IDPN-induced dyskinetic syndrome, we used the neurotoxin, 1-methyl, 4-phenyl,1,2,3,6-tetrahydropiridine (MPTP), as a tool for investigating which aspects of the IDPN-related syndrome could be due to enhanced dopaminergic activity in the neostriatum. In mice made permanently dyskinetic with IDPN, MPTP administration produced dramatic and biphasic effects on all behavioral patterns characteristics of the dyskinetic syndrome. Six weeks after the syndrome occurred, IDPN failed to produce any change in striatal DA levels with respect to controls. By contrast, IDPN seems to reduce striatal levels of extraneuronal metabolites of DA. These data suggest that the activity of the nigrostriatal dopaminergic pathway does not play a leading role in the maintenance of IDPN-related syndrome. The transient modification of all behavioral parameters immediately after MPTP administration could be explained by acute effects of MPTP on other dopaminergic areas which are not permanently lesioned by this neurotoxin, or by the acute effects of MPTP on the release of other neurotransmitters.

Alterations in the metabolism of serotonin and dopamine in the mouse brain following a single administration of allylnitrile, which induces long-term dyskinesia

The effects of allylnitrile (ALN), which induces a long-term dyskinesia in mice, on the metabolism of serotonin (5-HT) and dopamine (DA) were studied after a single administration. One day after injection, ALN produced a significant increase in the levels of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA): 5-HT in the brain cortex, medulla oblongata plus pons, hypothalamus and midbrain; 5-HIAA in the cortex, medulla oblongata plus pons, striatum, hypothalamus and midbrain; the ratio of 5-HIAA/5-HT in the medulla oblongata plus pons, striatum and midbrain; HVA in the cortex and midbrain. These changes were not seen 10 and 35 days after injection when the animals were showing behavioral abnormalities. The present findings suggest that changes in 5-HT and DA metabolism are involved in the appearance of the dyskinetic syndrome.