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ABSTRACT: Chunking of single movements into integrated sequences has been described during motor learning, and we have recently demonstrated
that this process involves a dopamine-dependant mechanism in animal (Levesque et al. in Exp Brain Res 182:499–508, 2007; Tremblay et al. in Behav Brain Res 198:231–239, 2009). However, there is no such evidence in human. The aim of the present study was to assess this question in Parkinson’s disease
(PD), a neurological condition known for its dopamine depletion in the striatum. Eleven PD patients were tested under their
usual levodopa medication (ON state), and following a 12-h levodopa withdrawal (OFF state). Patients were compared with 12
healthy participants on a motor learning sequencing task, requiring pressing fourteen buttons in the correct order, which
was determined by visual stimuli presented on a computer screen. Learning was assessed from three blocks of 20 trials administered
successively. Chunks of movements were intrinsically created by each participant during this learning period. Then, the sequence
was shuffled according to the participant’s own chunks, generating two new sequences, with either preserved or broken chunks.
Those new motor sequences had to be performed separately in a fourth and fifth blocks of 20 trials. Results showed that execution
time improved in every group during the learning period (from blocks 1 to 3). However, while motor chunking occurred in healthy
controls and ON-PD patients, it did not in OFF-PD patients. In the shuffling conditions, a significant difference was seen
between the preserved and the broken chunks conditions for both healthy participants and ON-PD patients, but not for OFF-PD
patients. These results suggest that movement chunking during motor sequence learning is a dopamine-dependent process in human.
KeywordsParkinson-Dopamine-Striatum-Motor learning-Movement-Sequence learning
Experimental Brain Research 04/2012; 205(3):375-385. · 2.39 Impact Factor
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ABSTRACT: Tardive dyskinesia (TD) is a neurological motor complication eventually arising in one-third of patients chronically exposed to antipsychotic drugs. Some orodental peripheral factors have been reported to influence TD.
To measure orodental factors such as temporomandibular joint function, static occlusal contacts, and denture condition, and attempt correlations with orofacial TD intensity.
In this exploratory cross-sectional pilot study, 31 subjects between 30 and 75 years of age were divided in two groups displaying minimal to mild, or moderate to severe orofacial TD, respectively, and underwent a detailed oral, dental, and prosthetic evaluation to capture various aspects of oral health compared between the two groups. Blinded video-based TD ratings along a validated scale were obtained to compare dentulous and edentulous subjects, and contrast TD intensity in complete denture wearers with and without their own prostheses.
None of the factors examined tightly correlated with orofacial TD intensity. However, edentulism was associated with a higher median orofacial TD rating compared to the dentulous group (p = 0.001). Further, a significant intra-subject difference was observed in the edentulous subjects rated with their own complete dentures in place or not (p = 0.028), the dentures attenuating the mean orofacial ratings by 21.8 ± 7.3%.
Of all orodental factors considered, only edentulism and complete denture wearing influenced oral TD expression, calling for the close monitoring of the dental status in antipsychotic drug-exposed patients to prevent tooth loss. Further studies to measure the impact of an adequate prosthodontic rehabilitation in edentulous subjects with orofacial TD seem warranted.
Journal of psychiatric research 03/2012; 46(5):684-7. · 3.72 Impact Factor
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ABSTRACT: Drug-induced parkinsonism (DIP) is seen in one third of patients exposed to antipsychotic drugs and may lead to complications related to dysphagia and falls. Aside from skilled neurological examination, no tool has been validated to facilitate detection and follow-up.
In this pilot study, three validated screening instruments were tested in an age-biased cohort of schizophrenia patients, including four items of the Liverpool University Neuroleptic Side-Effects Rating Scale (LUNSERS) and two brief questionnaires designed for community survey of parkinsonism.
Fifty-six subjects living with chronic schizophrenia between 50 and 75 years of age underwent a motor evaluation along the original Unified Parkinson's Disease Rating Scale-section III and answered questions along the selected screening instruments, and results compared to those of 16 patients with Parkinson's disease (PD) and 15 neurologically unimpaired volunteers. Odds ratios, sensitivity, specificity, and their 95% confidence intervals, were calculated.
All three screening instruments correctly identified the PD state and distinguished PD from healthy participants. Eighteen (32%) schizophrenic patients displayed objective motor signs of parkinsonism. A single item of the LUNSERS (shakiness) significantly distinguished DIP from DIP-free patients, with a sensitivity of 61.1% and a specificity of 83.3%. The positive predictive value was 63.5% and the negative predictive value was 81.9%. The two other screening methods showed insufficient predictive value.
Apart from a single query on shakiness, none of the tools examined were adequate to screen for DIP in patients treated for schizophrenia. A different instrument is necessary to monitor this important adverse effect in schizophrenia.
Biological Psychiatry 02/2012; 137(1-3):230-3. · 8.28 Impact Factor
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Biological Psychiatry 07/2011; 136(1-3):162-3. · 8.28 Impact Factor
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ABSTRACT: This study examined discrete motor irregularities in ballistic aiming movements in patients with atypical parkinsonian syndromes (APS). Nine patients with APS were compared to 9 patients with idiopathic Parkinson's disease (PD) and 9 controls on ballistic arm extension movements performed on a digitizing tablet without visual feedback and without accuracy constraints. Patients with APS showed a higher number of irregularities in the acceleration and jerk time series compared to PD patients and controls. No difference was found between PD patients and controls. These discrete irregularities were not associated with general motor impairment, tremor, akinesia, or rigidity. These results suggest that atypical parkinsonism is associated with movement irregularities in ballistic movements, which may help differentiate APS from PD.
Parkinsonism & Related Disorders 01/2009; 15(7):542-5. · 3.80 Impact Factor
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ABSTRACT: Motor learning disturbances have been shown in diseases involving dopamine insufficiency such as Parkinson's disease and schizophrenic patients under antipsychotic drug treatment. In non-human primates, motor learning deficits have also been observed following systemic administration of raclopride, a selective D2-receptor antagonist. These deficits were characterized by persistent fluctuations of performance from trial to trial, and were described as difficulties in consolidating movements following a learning period. Moreover, it has been suggested that these raclopride-induced fluctuations can result from impediments in grouping separate movements into one fluent sequence. In the present study, we explore the hypothesis that such fluctuations during movement consolidation can be prevented through the use of sumanirole - a highly selective D2 agonist - if administered before raclopride. Two monkeys were trained to execute a well known sequence of movements, which was later recalled under three pharmacological conditions: (1) no drug, (2) raclopride, and (3) sumanirole+raclopride. The same three pharmacological conditions were repeated with the two monkeys, trained this time to learn new sequences of movements. Results show that raclopride has no deleterious effect on the well known sequence, nor the sumanirole+raclopride co-administration. However, results on the new sequence to be learned revealed continuous fluctuations of performances in the raclopride condition, but not in the sumanirole+raclopride condition. These fluctuations occurred concurrently with a difficulty in merging separate movement components, known as a "chunking deficit". D2 receptors seem therefore to be involved in the consolidation of new motor skills, and this might involve the chunking of separate movements into integrated motor sequences.
Behavioural brain research 12/2008; 198(1):231-9. · 3.22 Impact Factor
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ABSTRACT: Edentulous orodyskinesia (ED) is a neglected source of aimless oral movements that may be confused with tardive dyskinesia (TD). We attempted to clarify the clinical features, significance, and orodental factors in relation to ED. Fourteen ED subjects, 13 TD patients, and 15 age-matched controls self-assessed their oral pain perception, condition, and function using a visual analogue scale. Dyskinesias were classified and rated by a neurologist. Perioral thermal and pressure pain threshold studies, and a standardized orodental examination, were conducted blind to subject group. The perceived oral pain level was low in all groups, and those reporting a significant intensity level of pain (>or=50th percentile) were few. The pain thresholds in both dyskinetic groups were comparable to control values. All ED cases wore a complete set of dentures, considered a current source of problems by 85.7% of them. ED cases commonly displayed inadequate dental occlusal relationship (P = 0.014 vs. controls; P = 0.036 vs. TD) and an overclosed vertical dimension (P = 0.006 vs. controls) as well as unstable and unretentive dentures. ED was limited to the oral region, spared the tongue when the mouth is open, and was never severe in our patients. ED has distinct movement characteristics and is often associated with inadequate dentures and biomechanical sources of denture instability. The contribution of the foregoing findings to the expression of oral dyskinesia warrants further studies.
Movement Disorders 09/2008; 23(13):1837-42. · 4.51 Impact Factor
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ABSTRACT: Oral dyskinesias occur in elderly individuals in relation to drug use (tardive dyskinesia, TD) or edentulousness (edentulous orodyskinesia, EOD) but their characterization remains incomplete. Our aim was to investigate whether magnetic resonance techniques such as diffusion-weighted imaging (DWI) and magnetization transfer imaging (MTI) of the brain could be used to differentiate dyskinetic patients from control subjects. Eight drug-treated patients with TD, 12 EOD patients, 8 drug-treated patients without TD, and 10 control subjects were recruited and examined by DWI and MTI. Measurements in the caudate nucleus, putamen, and globus pallidus yielded globally different apparent diffusion coefficient (ADC) values between drug treated patients with TD and control subjects but the magnetization transfer ratios showed no significant variations. The discrimination between dyskinetic patients and control subjects offered by ADC values was however slightly poorer than the discrimination offered by the previously published choline/creatine ratios measured by MR spectroscopy in the basal ganglia. The results are consistent with the pathophysiological hypothesis of damage to cholinergic interneurons.
Movement Disorders 06/2008; 23(9):1281-5. · 4.51 Impact Factor
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ABSTRACT: To characterize postural stability control and levodopa responsiveness in early Parkinson's disease (PD).
Postural sway was studied during quiet stance in ten patients within six years of PD onset, both before (OFF) and after (ON) regular oral levodopa dosing. Postural sway was recorded using a force platform during 30 sec with eyes open, and six dependent variables were examined.
Mild baseline subclinical changes in postural sway were recorded in our patients. Clear benefit was observed in five out of six characteristics (mean sway, transversal sway, sagittal sway, sway intensity, and sway area) in the ON condition.
Postural control mechanisms are affected early in PD and modulated by dopamine.
The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 04/2008; 35(1):65-8. · 0.97 Impact Factor
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ABSTRACT: Oral dyskinesias may occur spontaneously or be induced by medications such as antipsychotics and antidepressants. In this study, single voxel proton magnetic resonance spectroscopy was used to compare metabolite levels in the striatum for (1) 12 patients with drug-induced tardive dyskinesia (TD), (2) 12 patients with spontaneous oral dyskinesia (SOD), (3) 8 antidepressant-treated patients without TD, and (4) 8 control subjects. Statistically significant reductions in the choline/creatine (Cho/Cr) ratio were measured for the drug-treated patients with TD (-13%, P = 0.020) and SOD patients (-12%, P = 0.034) relative to control subjects. In comparison with antidepressant-treated patients without TD, drug-treated patients with TD showed a non statistically significant reduction in Cho/Cr (-11%, P = 0.079). All other metabolite ratios (N-acetylaspartate (NAA)/Cr, myo-inositol (mI)/Cr, glutamine + glutamate (Glx)/Cr, macromolecule + lipid (MM+Lip)/Cr, NAA/Cho) were unaffected by either type of dyskinesia. The observed Cho/Cr reduction in dyskinesia patients suggests decreased membrane phosphatidylcholine turnover, which provides free choline as precursor of molecules responsible for cellular signal transduction.
Movement Disorders 06/2007; 22(7):957-62. · 4.51 Impact Factor
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ABSTRACT: The physiological or pathological nature of subclinical tremor amplitude in Parkinson's disease (PD) is not well established. We analyzed characteristics of resting and postural tremors of subclinical amplitude in 17 patients with idiopathic PD without visible resting tremor, having a postural tremor in their least-affected hand rated 0 (12 subjects) or 1 (5 subjects) on Item 21 of the Unified Parkinson's Disease Rating Scale, compared to 17 control subjects matched for age, sex, and handedness. Tremor was recorded at the tip of the index finger using a displacement laser transducer. Overall results show that subclinical resting tremor in PD is significantly different from physiological tremor in terms of amplitude fluctuation, frequency dispersion, harmonic index, and proportional power in 4 to 6 Hz. No significant differences were found for postural tremor. These differences appear to originate mainly from patients with the mixed form of the disease. This study also confirms the preservation of physiological tremor likely originating from a distinct central oscillator in PD. The use of this method in the early and detailed characterization of PD tremors when amplitude is still within normal limits is proposed.
Movement Disorders 09/2005; 20(8):945-50. · 4.51 Impact Factor
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ABSTRACT: The prevalence and status of spontaneous oral dyskinesia (SOD), clinically defined as the presence of oral stereotypies of no apparent cause, remain controversial in the elderly. The reported high prevalence of SOD in institutionalized demented cases, the apparent similarity between SOD and tardive dyskinesia (TD), and the role of aging in both conditions, are used as arguments to minimise the prevalence of TD and causal role of antipsychotics. We observed 1,018 (69.3% women) noninstitutionalized, frail elderly subjects attending day care centers to document the prevalence and phenomenology of SOD. A total of 38 subjects, including 29 women, were suspected of having SOD, for a prevalence rate of 3.7% (95% confidence interval, 2.6-4.9%), 4.1% for women and 2.9% for men. A survey covering medical and dental issues was filled out by 508 volunteers. Subjects with suspected SOD reported more frequent ill-fitting dental devices (P = 0.002; odds ratio [OR] = 3.5), oral pain (P = 0.01; OR = 3.0), and a lower rate of perception of good oral health (P = 0.04; OR = 0.4) compared to nondyskinetics. Individuals with suspected SOD typically presented with mild stereotyped masticatory or labial movements compared to the more complex phenomenology of probable TD cases. Thus, SOD is comparatively infrequent in the elderly. The relation between its distinct orodental health profile and stereotyped manifestations warrants further attention.
Movement Disorders 09/2004; 19(8):892-6. · 4.51 Impact Factor
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Pierre J Blanchet,
Frédéric Calon,
Marc Morissette,
Abdallah Hadj Tahar,
Nancy Bélanger,
Pershia Samadi,
Richard Grondin,
Laurent Grégoire,
Leonard Meltzer,
Thérèse Di Paolo,
Paul J Bédard
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ABSTRACT: For nearly 20 years, the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) primate model has allowed great strides to be made in our understanding of the maladaptive changes underlying the levodopa-related motor response complications occurring in most parkinsonian patients. Studies indicate that sustained dopamine D2 receptor occupancy can prevent and reverse existing dyskinesias. Recent experiments in levodopa-treated MPTP animals, co-administered either a threshold dose of cabergoline or a glutamate NMDA NR2B-selective antagonist (CI-1041), have afforded protection against dyskinesia, perhaps through presynaptic inhibition of glutamate release and blockade of supersensitive postsynaptic NMDA receptors in the striatum, respectively. Some of the biochemical events that have correlated with dyskinesias, namely upregulated GABA(A) receptors in the internal pallidum, rise in pre-proenkephalin-A gene expression in the striatum, and upregulated striatal glutamate ionotropic receptors and adenosine A(2a) receptors, may be counteracted by these preventive strategies.
Parkinsonism & Related Disorders 08/2004; 10(5):297-304. · 3.80 Impact Factor
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ABSTRACT: NMDA receptor antagonists impair learning and memory in animal models, presumably by inhibiting long-term potentiation in the motor cortex. Human studies are limited and restricted by the paucity of safe NMDA antagonists. Here, we investigated the contribution of glutamatergic neurotransmission to the capacity of acquiring motor-adaptation learning in humans. In a double-blind design, 200 mg of amantadine (a low-affinity NMDA receptor channel blocker) or a matching placebo were given orally to groups of 14 and 13 human healthy young volunteers, respectively. Blood samples were collected 3 h after treatment to assay plasma concentrations, and the subjects were then tested using a motor-adaptation paradigm consisting of an eight-target-pointing task. To rule out drug-related generalized impairments such sedation, tests measuring motor dexterity and attention were also administered pre- and post-treatment. Comparison of the mean performance levels on the motor-adaptation task revealed that subjects in the amantadine group performed at a lower level than those in the placebo group, but this difference did not reach significance. Interestingly, however, despite plasma amantadine concentrations being relatively low, ranging from 2.09 to 4.74 microM (mean=3.3 microM), they nevertheless correlated negatively with motor learning. Furthermore, when the amantadine group was divided into low-performance and high-performance subgroups, subjects in the former subgroup displayed mean amantadine concentrations 36% higher than the latter subgroup, and performed significantly worser than the placebo group. No change in performance was found on the motor-dexterity and attention tests. Altogether, our results lend support to the hypothesis that normal NMDA receptor function is necessary for the acquisition of motor adaptation.
Neuropsychopharmacology 02/2004; 29(1):187-94. · 7.99 Impact Factor
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Pierre J Blanchet
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ABSTRACT: Although levodopa-related motor response complications remain challenging from a pathophysiological and therapeutic standpoint, major advances have been made in the last decade, supporting the development of several promising drugs. Eventually, these drugs may help us to prevent, alleviate, or even "deprime" these frequent and disabling complications. Knowledge of the basic mechanisms and hypotheses underlying this fascinating conversion in the parkinsonian brain allows neurologists to understand the rationale behind emerging treatment strategies.
The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 04/2003; 30 Suppl 1:S19-26. · 0.97 Impact Factor
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Pierre J Blanchet
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ABSTRACT: Very early in the process of diagnosing abnormal involuntary movement (AIM) disorders, one can be rewarded by keeping a high index of suspicion for possible drug-induced causes, not only through a complete list of current medications, but also identification of the drugs the patient used to take and other possible offending medications that might be available from family members and other sources. Among drug-induced movement disorders, antipsychotic drugs and other dopamine receptor blocking agents occupy a central place. Their various acute and tardive motor complications provide the template of this short review. Movement disorders caused by antidepressants, lithium, antiemetics, antiparkinsonian agents, anticonvulsants, calcium channel blockers, sympathomimetics and others are only briefly covered in table form.
The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 04/2003; 30 Suppl 1:S101-7. · 0.97 Impact Factor
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ABSTRACT: The effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced nigrostriatal lesion and dopaminomimetic treatment on parameters of glutamatergic activity within the basal ganglia of monkeys were studied in relation with the development of dyskinesias. Drug-naive controls, saline-treated MPTP monkeys, as well as MPTP monkeys treated with either a long-acting D2 agonist (cabergoline) or a D1 agonist (SKF-82958) given by intermittent injections or continuous infusion, were included in this study. 3H-L-glutamate, 3H-alpha-amino-3-hydroxy-5-methylisoxasole-4-propionate (AMPA), 3H-glycine, 3H-CGP39653 (an N-methyl-D-aspartate, NMDA, antagonist selective for NR1/NR2A assembly) and 3H-Ro 25-6981 (an NMDA antagonist selective for NR1/NR2B assembly), specific binding to glutamate receptors, the expression of the NR1 subunit of NMDA receptors and glutamate, glutamine and glycine concentrations were studied by autoradiography, in situ hybridization and high-performance liquid chromatography (HPLC), respectively. Pulsatile SKF-82958 and cabergoline treatment relieved parkinsonian symptoms, whereas animals continuously treated with SKF-82958 remained akinetic. Pulsatile SKF-82958 induced dyskinesias in two of the three animals tested, whereas cabergoline did not. MPTP induced no significant changes of striatal specific binding of the radioligands used, NR1 mRNA expression and amino acid concentrations. In the putamen, pulsatile SKF-82958 treatment was associated with decreased content of glycine and glutamate, whereas only glycine was decreased in cabergoline-treated monkeys. Cabergoline and continuous administration of SKF-82958 led to lower levels of NR1 mRNA in the caudate in comparison to pulsatile SKF-82958 administration. The development of dyskinesias following a D1 agonist treatment was associated with an upregulation of 3H-glutamate [+49%], 3H-AMPA [+38%], 3H-CGP39653 [+ 111%], 3H-glycine [+ 26%, nonsignificant] and 3H-Ro 25-6981 [+ 33%] specific binding in the striatum in comparison to nondyskinetic MPTP monkeys. Our data suggest that supersensitivity to glutamatergic input in the striatum might play a role in the pathogenesis of dopaminomimetic-induced dyskinesias and further support the therapeutic potential of glutamate antagonists in Parkinson's disease.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 02/2002; 26(1):127-38. · 3.25 Impact Factor
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ABSTRACT: We investigated the effect of MPTP-induced lesion of the substantia nigra pars compacta (SNpc) dopaminergic neurons on GABAB receptors in the basal ganglia of mice and monkeys using receptor autoradiography and in situ hybridization. The extent of the lesion was measured with striatal catecholamine content, striatal binding of 125I-RTI-121 to dopamine transporter (DAT), and DAT expression in the SNpc. GABAB receptors in mice brain were evaluated using 3H-CGP54626 and its expression was measured with oligonucleotides probes targeting the mRNAs of GABAB(1a+b), GABAB(1a), GABAB(1b), GABAB(2) subunits. In monkeys, 125I-CGP64213 and selective probes for GABAB(1a+b) and GABAB(2) mRNAs were used. In mice, dopamine content, 125I-RTI-121 binding, and DAT expression were reduced by 44%, 40%, and 39% after a dose of 40 mg/kg of MPTP and 74%, 70%, and 34% after 120 mg/kg of MPTP, respectively. In monkeys, dopamine content and DAT expression were decreased by more than 90% and 80%, respectively. In the striatum and the subthalamic nucleus, GABAB receptors were unchanged following MPTP in both species. In the SNpc of mice, MPTP (120 mg/kg) induced a significant decrease of 3H-CGP54626 binding (−10%) and of the expression of GABAB(1a+b) mRNA (−13%). The decrease of the expression of GABAB(1a+b) mRNA was correlated with dopamine content, 125I-RTI-121 binding and DAT expression. In MPTP-treated monkeys, 125I-CGP64213 binding (−40%), GABAB(1a+b) mRNA (−69%) and GABAB(2) mRNA (−66%) were also significantly decreased in the SNpc. Our results suggest that MPTP-induced denervation is associated with a decrease of GABAB receptors restricted to the SNpc. These observations may be relevant to the pathophysiology of motor disorders involving dysfunction of the basal ganglia such as Parkinson disease. Synapse 40:225–234, 2001. © 2001 Wiley-Liss, Inc.
Synapse 04/2001; 40(3):225 - 234. · 2.94 Impact Factor
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ABSTRACT: Dentists may be the first health care professionals to recognize unusual and abnormal oral movements collectively termed oral dyskinesias. The aims of this clinical overview are to raise the dental community's awareness about this important and complex topic and describe the clinical features and management of the main entities.
A MEDLINE search of the different entities reported in the English and French literature was conducted. The main findings of a field study on oral dyskinesia were also reviewed.
Involuntary movement disorders are often drug related. In other cases, excessive oral movements may occur at any age in relation to various neuropsychiatric conditions. Orofacial dystonia apparently triggered by dental procedures has also been reported. Edentulousness has been associated with oral stereotypes. In a survey of 352 edentulous elderly individuals attending daycare centers, only 7% displayed visible oral sterotypes, and ill-fitting dentures were suggested as a possible triggering factor for the majority.
A multidisciplinary evaluation is desirable in the care of individuals with oral dyskinesia and in the selection of those who may benefit from a prosthodontic approach. A good knowledge of potentially offending drugs may allow avoidance of unnecessary procedures.
The International journal of prosthodontics 18(1):10-9. · 1.38 Impact Factor
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ABSTRACT: Much evidence indicates that abnormal GABA neurotransmission may be implicated in the pathophysiology of Parkinson's disease (PD) and dopaminomimetic-induced dyskinesias (DID). In this study, autoradiography using 125I-CGP 64213 was performed to investigate GABAB receptor density in the brain of control monkeys as well as monkeys with MPTP-induced nigrostriatal depletion. Three MPTP monkeys received pulsatile administrations of the D1 dopamine (DA) receptor agonist (SKF 82958) whereas a long-acting D2 DA receptor agonist (cabergoline) was given to another three animals. SKF 82958 treatment relieved parkinsonian symptoms but two of three animals developed DID. Cabergoline induced a comparable motor benefit effect without persistent DID. 125I-CGP 64213 binding to GABAB receptors was heterogeneous throughout the brain with the highest levels in the medial habenula of the thalamus. MPTP induced a decrease (−40%) of 125I-CGP 64213 binding to GABAB receptors in the substantia nigra pars compacta (SNpc) and an increase (+29%) in the internal segment of the globus pallidus (GPi). This increase in the GPi was not affected by SKF 82958 but partly reversed by cabergoline. No change was seen in the striatum, the thalamus, the external segment of the globus pallidus, and the substantia nigra pars reticulata following MPTP and dopaminomimetic treatments. The changes of GABAB receptors observed in the SNpc and in the GPi suggest that alteration of GABAB receptors may play a role in the pathophysiology of PD and DID.
Experimental Neurology.
