[Genuine motor phenomena in schizophrenic psychoses : Theoretical background and definition of context]. / Genuine motorische Phänomene bei schizophrenen Psychosen : Theoretischer Hintergrund und Kontextdefinition.

Besides positive and negative symptoms, motor abnormalities have been increasingly recognized as central symptoms of schizophrenia. Recent investigations of antipsychotic-naive first-episode patients with schizophrenia found significantly higher rates of genuine motor abnormalities (GMA) when compared to healthy individuals. The first part of this article introduces the historical and clinical background of GMA in schizophrenia. In the second part the relevance of scientific research and clinical implication of GMA in schizophrenia are discussed. Finally, this article aims at presenting a conceptual framework and a reference system involving both genuine and drug-induced motor abnormalities. The future clinical implications of GMA research are presented and multimodal and transdiagnostic studies are advocated. Future research on GMA will not only essentially enrich the formation of psychiatric theories but also promote progress in clinical neuroscience.

A new quantitative rating scale for dyskinesia in nonhuman primates.

The aim of this study was to develop a quantitative scale to assess levodopa-induced dyskinesias (LIDs) in nonhuman primates using a video-based scoring system [Quantitative Dyskinesia Scale (QDS)]. Six macaques with stable Parkinsonism and LID were used for tests of the new QDS, in comparison with our current standardized scale (Drug-Related Side effects), which provides a classic subjective measurement of dyskinesia. QDS scoring is based on systematic movement counts in time frames, using videotape recordings. For both scales, body segments scored included each extremity, the trunk, the neck, and the face, and raters were blinded to L-dopa treatments. Comparison of the two scales revealed that their scores are highly correlated with and are parallel to the L-dopa pharmacokinetic profile, although the QDS provided significantly more quantifiable measurements. This remained the case after separating animals into groups of mild and severe dyskinesias. Inter-rater reliability for application of the QDS was confirmed from scores obtained by three examiners. We conclude that the QDS is a quantitative tool for reliably scoring LID in parkinsonian monkeys at all levels of severity of dyskinesia. The application of this new standard for scoring LID in primates will allow for more precise measurements of the effects of experimental treatments and will improve the quality of results obtained in translational studies.

Differential genetic susceptibility in diphasic and peak-dose dyskinesias in Parkinson's disease.

To examine whether there is a differential genetic susceptibility in the diphasic and peak-dose forms of levodopa-induced dyskinesias (LID) in patients with Parkinson's disease (PD). The study cohort comprised 503 unrelated Korean PD patients who were treated with levodopa and had a disease duration of at least 5 years. The presence of LID was identified during a routine follow-up and special care was taken to separate the two distinct forms of LID into diphasic and peak-dose dyskinesias (PDSK). Genotyping was performed in the 503 patients and in 559 healthy controls to search for polymorphisms of DRD3 p.S9G, DRD2 Taq1A, GRIN2B c.2664C>T, c.366C>G, c.-200T>G, and the promoter region of SLC6A4. A total of 229 patients expressed LID (peak-dose in 205, diphasic in 57, and both in 33). The presence of diphasic dyskinesia (DDSK) was exclusively associated with the DRD3 p.S9G variant after adjusting for gender, age at PD onset, Hoehn & Yahr stage, and duration of levodopa treatment. Carrying the AA genotype was likely to shorten the onset of DDSK according to the duration of levodopa therapy (P = 0.02). The presence of PDSK was not significantly associated with any of the six genetic variants studied. There may be a genetic susceptibility in the development of DDSK in PD patients on chronic levodopa therapy, and its underlying pathophysiological mechanism might be distinct from that of PDSK.

Neuroleptic-induced tardive cervical dystonia: clinical series of 20 patients.

BACKGROUND: Cervical dystonia (CD) may be classified according to the underlying cause into primary or secondary CD. Previous exposure to neuroleptics is one of the main causes of adult-onset secondary dystonia. There are few reports that characterize the clinical features of primary CD and secondary neuroleptic-induced CD. Herein our aim was to investigate a series of patients with neuroleptic induced tardive CD and to describe their clinical and demographic features. PATIENTS AND METHODS: We retrospectively evaluated 20 patients with neuroleptic-induced tardive CD and compared clinical, demographic and therapeutic characteristics to another 77 patients with primary CD. All patients underwent Botulinum toxin type-A therapy. RESULTS: We did not identify any relevant clinical and demographic characteristics in our group of patients that could be used to distinguish tardive and primary CD. CONCLUSION: Patients with tardive CD presented demographic characteristics and disease course similar to those with primary CD.

Quantifying drug induced dyskinesia in Parkinson's disease patients using standardized videos.

This paper presents a video based method to quantify drug induced dyskinesias in Parkinson's disease (PD) patients. Dyskinetic movement in standard clinical videos of patients is analyzed by tracking landmark points on the video frames using non-rigid image registration. The novel application of Point Distribution Models (PDM) allows geometric variations and covariations of the landmark points to be captured from each video sequence. The PDM parameters represent quantifiable information that can be used to rate dyskinesia effectively, analogously to a neurologist's strategy of assessing the movement of multiple body parts simultaneously to effectively rate dyskinesia. A heuristic decision function is then developed using the PDM parameters to quantify the severity of the dyskinesia. The severity score using our decision function showed a high correlation to the dyskinesia rating of a neurologist on the corresponding patient videos.

Comparative assessment of the incidence and severity of tardive dyskinesia in patients receiving aripiprazole or haloperidol for the treatment of schizophrenia: a post hoc analysis.

OBJECTIVE: To comparatively assess the incidence of tardive dyskinesia in patients with schizophrenia receiving either aripiprazole or haloperidol. METHOD: Data from 2 controlled, long-term trials of subjects meeting DSM-IV criteria for schizophrenia treated with aripiprazole (N = 861, 20-30 mg/day) or haloperidol (N = 433, 5-10 mg/day) were analyzed. The primary outcome measure was the rate of new-onset tardive dyskinesia. The analysis was limited to patients without baseline tardive dyskinesia. There were no significant differences between treatment groups in demographic or disease characteristics. The Abnormal Involuntary Movement Scale (AIMS) and Research Diagnostic Criteria for tardive dyskinesia were used to define the comparative incidence rates of long-term treatment-emergent tardive dyskinesia. RESULTS: A significantly lower percentage of aripiprazole-treated patients developed new-onset tardive dyskinesia compared with haloperidol-treated patients (p < .0001). The annualized rate of treatment-emergent tardive dyskinesia was significantly lower in aripiprazole-treated versus haloperidol-treated patients. In patients without a baseline diagnosis of tardive dyskinesia, aripiprazole significantly improved AIMS scores compared with haloperidol (p

Discinesias induzidas por drogas / Drug-induced dyskinesias

Baseados em extensa revisão da literatura, os autores analisam o conceito, a fenomenologia, a fisiopatologia e o tratamento atual dos diversos movimentos anormais induzidos por drogas. Dentre estes são abordados a acatisia, o balismo, a distonia, a mioclonia, o tique, o tremor e o parkinsonismo, enfatizando, ao final, as discinesias tardias e as induzidas pela levodopa.

A critical review of rating scales in the assessment of movement disorders in schizophrenia.

Tardive dyskinesia (TD) has been recognised for nearly 50 years. It is associated with antipsychotic drugs and is usually persistent with no satisfactory treatment. It is believed to be under-documented in medical records. Many rating scales have been devised to measure TD. Studies have demonstrated variability between the rating scales on the measures of reliability and validity, the clinical setting used, the raters involved in the ratings and the provision of definitions and instructions. Scales that include too many items to be comprehensive become cumbersome and difficult to use. A compromise is to reduce the number of items and have add-in items for individual patients. A good example of this approach is the Abbreviated Dyskinesia Scale (ADS). Rating scales continue to be the best available methods to evaluate dyskinesia but in view of the shortcomings of validity, reliability and utility for clinical use, more efforts need to be done to improve current rating scales and to develop new ones.

Prognosis of Parkinson's disease: time to stage III, IV, V, and to motor fluctuations.

We report a long-term outcome on a large cohort of Japanese patients with Parkinson's disease (PD). A total of 1,768 (793 men, 975 women) consecutive patients visited our clinic from 1 January 1989 to 31 December 2002. Among them, 1,183 patients (531 men, 652 women) came to our clinic within 5 years from the onset of disease and at the Hoehn & Yahr Stage III or less at the first visit. Long-term outcome was evaluated in this subcohort of the patients. We examined the duration to reach Stage III, IV, and V, and the duration to develop wearing off and dyskinesia. Time to reach Stage III was slightly but significantly shorter in women, in that 23.8% of men and 35.3% of women reached Stage III by the end of the 5th year; 49.7% of men and 63.3% of women reached Stage III by the end of the 10th year, and 88.9% of men and 79.9% of women by the end of the 15th year (P < 0.001). Also, durations to develop wearing off and dyskinesia were shorter in women compared to men. These data suggest that the disease progression may be slightly faster for women. Young-onset patients showed significantly longer duration to reach Stage III, IV, and V but shorter duration to develop wearing off and dyskinesia. Not many studies are available in the literature on the long-term outcome of PD, and our data would be useful as a reference.

Prevalence of spontaneous oral dyskinesia in the elderly: a reappraisal.

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.

New nomenclature for drug-induced movement disorders including tardive dyskinesia.

Psychotropic agents are increasingly being prescribed by different specialty clinicians for a variety of psychiatric illnesses, making it necessary to improve understanding of the etiology, diagnosis, and management of drug-induced movement disorders (D-IMD) across medical specialties. Early descriptions of movement disorders were based on identifiable disease states such as parkinsonism, dystonia deformans, and Huntington's chorea, which introduced complicated and often overlapping nomenclature. This has hindered communication about, description of, and diagnosis of these drug-induced disorders. Research criteria for tardive dyskinesia, a specific, purposeless, involuntary, hyperkinetic, potentially persistent D-IMD, have varied, with relatively few data-driven conclusions available to support clinical decision-making. The differences in research criteria among published reports on rates of tardive dyskinesia with atypical antipsychotics make it difficult to find meaningful comparisons and conclusions between atypicals. A novel system for classifying D-IMD according to whether they are reversible or persistent, hypokinetic or hyperkinetic, and dystonic or nondystonic is proposed. This new classification system will provide clinicians and researchers across specialties a more precise language, which will hopefully improve the diagnosis of and research criteria for D-IMD.

Automatic assessment of levodopa-induced dyskinesias in daily life by neural networks.

We developed an objective and automatic procedure to assess the severity of levodopa-induced dyskinesia (LID) in patients with Parkinson's disease during daily life activities. Thirteen patients were continuously monitored in a home-like situation for a period of approximately 2.5 hours. During this time period, the patients performed approximately 35 functional daily life activities. Behavior of the patients was measured using triaxial accelerometers, which were placed at six different positions on the body. A neural network was trained to assess the severity of LID using various variables of the accelerometer signals. Neural network scores were compared with the assessment by physicians, who evaluated the continuously videotaped behavior of the patients off-line. The neural network correctly classified dyskinesia or the absence of dyskinesia in 15-minute intervals in 93.7, 99.7, and 97.0% for the arm, trunk, and leg, respectively. In the few cases of misclassification, the rating by the neural network was in the class next to that indicated by the physicians using the AIMS score (scale 0-4). Analysis of the neural networks revealed several new variables, which are relevant for assessing the severity of LID. The results indicate that the neural network can accurately assess the severity of LID and could distinguish LID from voluntary movements in daily life situations.

[Dyskinesia caused by L-DOPA]. / Dyskinésies provoquées par la L-DOPA.

L-DOPA-induced dyskinesias are a common problem, occurring in about one third of parkinsonian patients after five years of treatment. Young age of onset, disease severity, duration of therapy and total dose of L-DOPA are the variables that best correlate with the development of dyskinesias. The first manifestations of dyskinesia are usually dystonic and involve the foot homolateral to the side most affected by Parkinson's disease. With time, dyskinesias may be classified in three main categories: off dystonia, diphasic dyskinesias also called "onset and end of dose dyskinesia" and peak dose dyskinesia. Although this classification is very useful in clinical practice, the different types of dyskinesia frequently overlap in a single patient when the disease progresses. Other types of involuntary movements such as myoclonus, a tremor with an increased amplitude and akathisia have been described. The physiopathology of L-DOPA-induced dyskinesias remains unclear but synaptic plasticity in striatal neurons seems to be a major phenomenon in the development of dyskinesias. Some rating scales have been developed to assess the intensity and severity of dyskinesias but their usefulness is still matter of debate.

Workshop III: late motor complications of Parkinson's disease.

The aim in the current treatment of Parkinson's disease is to delay L-Dopa administration and to keep the L-Dopa dosage as low as possible. Such a treatment strategy can delay the onset of late motor complications and reduce their severity. L-Dopa remains the most potent anti-parkinsonian medication, but its use for the initial therapy of Parkinson's disease is limited to elderly patients. In all other cases, dopamine agonists, budipine, amantadine and selegiline are primarily used. With the occurrence of late motor complications continuous dopamine receptor stimulation becomes essential. In this situation, combination therapy has to be individualized, with dopamine agonists playing a key role. In addition, COMT inhibitors, budipine, amantadine and selegiline may be used. Anticholinergic drugs are of very limited importance in the current treatment of Parkinson's disease.

Catatonia and other motor syndromes in a chronically hospitalized psychiatric population.

BACKGROUND: To determine the motor characteristics of chronic catatonia, catatonia and other motor disorders were systematically rated in a long-term hospitalized sample. METHOD: Chronically hospitalized psychiatric inpatients (N = 42) with a clinical diagnosis of catatonic schizophrenia (295.2X) were rated for catatonia with a novel 23-item catatonia rating scale, and for parkinsonism, dyskinesia and akathisia using standard rating scales with scale-based criteria for case definition. RESULTS: Catatonia was the sole motor syndrome in nine cases (21%), co-existed with parkinsonism in five (12%), tardive dyskinesia in four (10%), and both parkinsonism and tardive dyskinesia in 10 (24%). There was no correlation between total scores across the four rating scales. 'Rigidity' was the sole catatonic sign which overlapped with other scales. The symptom profile of catatonia in this chronic sample was similar to previous reports based on acutely ill patients. CONCLUSION: Catatonia is distinguishable from other motor disorders in chronic psychiatric patients using the 23-item catatonia rating scale. The features of chronic catatonia are described, and the distribution of catatonic signs is similar for chronic and acute catatonia.

[Alexithymia in negative symptom and non-negative symptom schizophrenia]. / L'alexithymie chez des schizophrènes déficitaires et non déficitaires.

Coined by Sifneos in 1972, alexithymia refers to a relative narrowing in emotional functioning, an inability to find appropriate words to describe their emotions and, a poverty of fantasy life. Although initially described in the context of psychosomatic illness, alexithymic characteristics may be observed in patients with a wide range of medical and psychiatric disorders: Parkinson disease, depression, anxiety, substance abuse and eating disorders. Flattening of affect and poverty of speech, major negative symptoms, referred to chronic schizophrenia: there is a lack of outward display of emotion. Accordingly, some disturbances of alexithymia's scores would be expected in schizophrenic patients. The purpose of this study was to estimate and compare the prevalence of alexithymia in deficit and non-deficit schizophrenia. The term "deficit symptoms" may be used as Carpenter, to refer specifically to those negative symptoms that are not considered secondary. The influence of patients' symptoms has also been studied on alexithymia scores: negative and positive symptoms of schizophrenia, depression, anxiety, anhedonia and effects of neuroleptics. Twenty-five patients, meeting DSM III-R criteria for schizophrenia have been studied. All of them treated by neuroleptics, were in a stable clinical status for at least one month. The patients have been categorized into deficit (n = 12) and non-deficit (n = 13) subgroups by one trained psychiatrist (SD), using the Schedule for the Deficit Syndrome. The subjects have been assessed by the same rater (IN), blind to deficit status, using six rating scales: Beth Israel Questionnaire (BIQ) and Toronto Alexithymia Scale (TAS) for alexithymia, Positive and Negative Syndrome Scale (PANSS), Montgomery and Asberg Depression Rating Scale (MADRS), revised Physical Anhedonia Scale (PAS), and finally, Extrapyramidal Symptom Rating Scale (ESRS). Using TAS, alexithymic characteristics were more prevalent in the deficit subgroup as compared to non-deficit subgroup (83% versus 30.76%; p < 0.01). Significant correlations were observed in the non-deficit subgroup between: TAS and anxiety (r = 0.743; p < 0.01), TAS and depression (r = 0.568; p < 0.05), BIQ and blunted affect (r = 0.636; p < 0.02), BIQ and poverty of speech (r = 0.629; p < 0.02). These correlations were not significant in the deficit group of patients. Alexithymia in schizophrenic patients seems to be a trait characteristic in deficit patients, and a state related to many symptoms, such as flattening of affect, poverty of speech, depression and anxiety in nondeficit patients.