Diagnostic prediction model for levodopa-induced dyskinesia in Parkinson's disease / Modelo de predição diagnóstica para discinesias induzidas por levodopa na doença de Parkinson

Abstract Background: There are currently no methods to predict the development of levodopa-induced dyskinesia (LID), a frequent complication of Parkinson's disease (PD) treatment. Clinical predictors and single nucleotide polymorphisms (SNP) have been associated to LID in PD. Objective: To investigate the association of clinical and genetic variables with LID and to develop a diagnostic prediction model for LID in PD. Methods: We studied 430 PD patients using levodopa. The presence of LID was defined as an MDS-UPDRS Part IV score ≥1 on item 4.1. We tested the association between specific clinical variables and seven SNPs and the development of LID, using logistic regression models. Results: Regarding clinical variables, age of PD onset, disease duration, initial motor symptom and use of dopaminergic agonists were associated to LID. Only CC genotype of ADORA2A rs2298383 SNP was associated to LID after adjustment. We developed two diagnostic prediction models with reasonable accuracy, but we suggest that the clinical prediction model be used. This prediction model has an area under the curve of 0.817 (95% confidence interval [95%CI] 0.77‒0.85) and no significant lack of fit (Hosmer-Lemeshow goodness-of-fit test p=0.61). Conclusion: Predicted probability of LID can be estimated with reasonable accuracy using a diagnostic clinical prediction model which combines age of PD onset, disease duration, initial motor symptom and use of dopaminergic agonists.

Resumo Introdução: No momento, não há métodos para se predizer o desenvolvimento de discinesias induzidas por levodopa (DIL), uma frequente complicação do tratamento da doença de Parkinson (DP). Preditores clínicos e polimorfismos de nucleotídeo único (SNP) têm sido associados às DIL na DP. Objetivo: Investigar a associação entre variáveis clínicas e genéticas com as DIL e desenvolver um modelo de predição diagnóstica de DIL na DP. Métodos: Foram avaliados 430 pacientes com DP em uso de levodopa. A presença de DIL foi definida como escore ≥1 no item 4.1 da MDS-UPDRS Parte IV. Nós testamos a associação entre variáveis clínicas específicas e sete SNPs com o desenvolvimento de DIL, usando modelos de regressão logística. Resultados: Em relação às variáveis clínicas, idade de início da doença, duração da doença, sintomas motores iniciais e uso de agonistas dopaminérgicos estiveram associados às DIL. Apenas o genótipo CC do SNP rs2298383 no gene ADORA2A esteve associado com DIL após o ajuste. Nós desenvolvemos dois modelos preditivos diagnósticos com acurácia razoável, mas sugerimos o uso do modelo preditivo clínico. Esse modelo de predição tem uma área sob a curva de 0,817 (intervalo de confiança de 95% [IC95%] 0,77‒0,85) e sem perda significativa de ajuste (teste de qualidade de ajuste de Hosmer-Lemeshow p=0,61). Conclusão: A probabilidade prevista de DIL pode ser estimada, com acurácia razoável, por meio do uso de um modelo preditivo diagnóstico clínico, que combina a idade de início da doença, duração da doença, sintomas motores iniciais e uso de agonistas dopaminérgicos.

Effects and molecular mechanism of chitosan-coated levodopa nanoliposomes on behavior of dyskinesia rats

BACKGROUND: Chitosan, the N-deacetylated derivative of chitin, is a cationic polyelectrolyte due to the presence of amino groups, one of the few occurring in nature. The use of chitosan in protein and drug delivery systems is being actively researched and reported in the literature RESULTS: In this study, we used chitosan-coated levodopa liposomes to investigate the behavioral character and the expression of phosphorylated extracellular signal-regulated kinase (ERK1/2), dopamine- and cAMP-regulated phos-phoprotein of 32 kDa (DARPP-32) and FosB/AFosB in striatum of rat model of levodopa-induced dyskinesia (LID). We found that scores of abnormal involuntary movement (AIM) decreased significantly in liposome group (P < 0.05), compared with levodopa group. Levels of phospho-ERK1/2, phospho-Thr34 DARPP-32 and FosB/AFosB in striatum decreased significantly in liposome group lesion side compared with levodopa group (P < 0.05). However, both of two groups above have significantly differences compared with the control group (P < 0.05). CONCLUSION: Chitosan-coated levodopa liposomes may be useful in reducing dyskinesias inducing for Parkinson disease. The mechanism might be involved the pathway of signaling molecular phospho-ERK1/2, phospho-Thr34 DARPP-32 and AFosB in striatum

Effect of Subthalamic Deep Brain Stimulation on Levodopa-Induced Dyskinesia in Parkinson's Disease

PURPOSE: To evaluate the effect of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) on levodopa-induced peakdose dyskinesia in patients with Parkinson's disease (PD). MATERIALS AND METHODS: A retrospective review was conducted on patients who underwent STN DBS for PD from May 2000 to July 2012. Only patients with levodopa-induced dyskinesia prior to surgery and more than 1 year of available follow-up data after DBS were included. The outcome measures included the dyskinesia subscore of the Unified Parkinson's Disease Rating Scale (UPDRS) part IV (items 32 to 34 of UPDRS part IV) and the levodopa equivalent daily dose (LEDD). The patients were divided into two groups based on preoperative to postoperative LEDD change at 12 months after the surgery: Group 1, LEDD decrease >15%; Group 2, all other patients. Group 2 was further divided by the location of DBS leads. RESULTS: Of the 100 patients enrolled, 67 were in Group 1, while those remaining were in Group 2. Twelve months after STN DBS, Groups 1 and 2 showed improvements of 61.90% and 57.14%, respectively, in the dyskinesia subscore. Group 1 was more likely to experience dyskinesia suppression; however, the association between the groups and dyskinesia suppression was not statistically significant (p=0.619). In Group 2, dyskinesia was significantly decreased by stimulation of the area above the STN in 18 patients compared to stimulation of the STN in 15 patients (p=0.048). CONCLUSION: Levodopa-induced dyskinesia is attenuated by STN DBS without reducing the levodopa dosage.

Overweight is more prevalent in patients with Parkinson's disease / Excesso de peso é mais frequente em pacientes com doença de Parkinson

Underweight and malnutrition are well documented in Parkinson's disease (PD), while overweight has been less reported. We carried out a cross-sectional study including 177 healthy controls and 177 PD patients attending a tertiary care center. We recorded weight and height for all participants. A statistically significant difference was found in body mass index (BMI) between controls and PD patients (29.1±5.4 versus 27.2±4.7, p<0.001). In the PD Group, two patients were underweight, 32.7% were within normal range, 46.9% had overweight, and 19.2% were obese. Overweight and normal weight were more prevalent in the PD Group (p=<0.01 and <0.001, respectively) when compared to controls. In conclusion, overweight/obesity are common among patients with PD, while underweight is almost negligible.

Baixo peso e desnutrição são muito documentadas na doença de Parkinson (DP), enquanto que o excesso de peso tem sido menos relatado. Foi realizado um estudo transversal com 177 controles saudáveis e 177 pacientes com DP que frequentavam um centro terciário. O peso e a altura de todos os participantes foram arquivados. Uma diferença estatisticamente significativa no índice de massa corporal (IMC) foi encontrada entre controles e pacientes com DP (29,1±5,4 versus 27,2±4,7, p<0,001). No Grupo DP, dois pacientes estavam abaixo do peso, 32,7% estavam dentro do intervalo normal, 46,9% apresentavam sobrepeso e 19,2% eram obesos. Peso normal e excesso de peso foram mais prevalentes no Grupo DP (p=<0,01 e <0,001, respectivamente) em relação aos controles. Em conclusão, o sobrepeso/obesidade são comuns entre os pacientes com DP, enquanto baixo peso nessa população é quase insignificante.

Lees' syndrome: a case series / Síndrome de Lees: uma série de casos

We report a case series of dopamine dysregulation syndrome, previously known as hedonistic homeostatic dysregulation in patients with Parkinson's disease on dopamine replacement therapies, now designated as Lees' syndrome.

Relatamos uma série de casos da síndrome de desregulação dopaminérgica, previamente conhecida como desregulação homeostática hedonística em pacientes com doença de Parkinson em uso de terapia de reposição dopaminérgica, e agora definida como síndrome de Lees.

Lack of tolerance for the anti-dyskinetic effects of 7-nitroindazole, a neuronal nitric oxide synthase inhibitor, in rats

7-Nitroindazole (7-NI) inhibits neuronal nitric oxide synthase in vivo and reduces l-DOPA-induced dyskinesias in a rat model of parkinsonism. The aim of the present study was to determine if the anti-dyskinetic effect of 7-NI was subject to tolerance after repeated treatment and if this drug could interfere with the priming effect of l-DOPA. Adult male Wistar rats (200-250 g) with unilateral depletion of dopamine in the substantia nigra compacta were treated with l-DOPA (30 mg/kg) for 34 days. On the 1st day, 6 rats received ip saline and 6 received ip 7-NI (30 mg/kg) before l-DOPA. From the 2nd to the 26th day, all rats received l-DOPA daily and, from the 27th to the 34th day, they also received 7-NI before l-DOPA. Animals were evaluated before the drug and 1 h after l-DOPA using an abnormal involuntary movement scale and a stepping test. All rats had a similar initial motor deficit. 7-NI decreased abnormal involuntary movement induced by l-DOPA and the effect was maintained during the experiment before 7-NI, median (interquartile interval), day 26: 16.75 (15.88-17.00); day 28: 0.00 (0.00-9.63); day 29: 13.75 (2.25-15.50); day 30: 0.5 (0.00-6.25); day 31: 4.00 (0.00-7.13), and day 34: 0.5 (0.00-14.63), Friedman followed by Wilcoxon test,vs day 26, P < 0.05;. The response to l-DOPA alone was not modified by the use of 7-NI before the first administration of the drug (l-DOPA vs time interaction, F1,10 = 1.5, NS). The data suggest that tolerance to the anti-dyskinetic effects of a neuronal nitric oxide synthase inhibitor does not develop over a short-term period of repeated administration. These observations open a possible new therapeutic approach to motor complications of chronic l-DOPA therapy in patients with Parkinson’s disease.

[Spinophilin gene expression in 6-OHDA-lesioned rat model of parkinson's disease and L-DOPA-induced dyskinesia]

The hypothesis that alterations of proteins that mediate dopaminergic signal transduction might be involved in the altered dopaminergic receptors in Parkinson's disease and L-DOPA-induced dyskinesia was explored. We measured transcript expression of spinophilin, a protein enriched in.dendritic spines that modulates excitatory neurotransmission and involved in dopamine [DA] signaling in the striatum and cerebral cortex of 6- hydroxydopamine [6-OHDA-lesioned rats model of Parkinson's disease and following chronic treatment with L-DOPA which induces dyskinesia [L-DOPA-induced dyskinesia LID]. The transcript encoding spinophilin, was decreased by 27% and 18% respectively in, lesioned and unlesioned sides of the rostral striatum. Acute and chronic treatment with L- DOPA produced an increase in transcript levels of spinophilin in the rostral and caudal striatum, and somatosensory cortex but not in the motor cortex. These alterations in spinophilin and mRNA levels in 6-OHDA-Iesioned rat model of Parkinson's disease and L-DOPA-induced dyskinesia provide further evidence for the role of spinophilin in the neural mechanisms underlying altered dopaminergic receptors in PD and LID

Distonia aguda relacionada ao uso de bromoprida em pacientes pediátricos / Acute dystonia after use of bromopride in pediatric patients

OBJETIVO: Descrever dois casos de distonia aguda após uso de bromoprida em crianças e realizar revisão da literatura em relação aos mecanismos fisiopatológicos de indução de liberação extrapiramidal, sua sintomatologia e tratamento. DESCRIÇÃO DO CASO: Caso 1: adolescente de 13 anos com quadro de dor e hipertonia cervical associados a febre, náuseas e vômitos, com hipótese inicial de meningite. A investigação subsequente revelou que o quadro iniciou-se após ingestão de uma única dose de bromoprida. O paciente apresentou boa resposta ao tratamento com difenidramina, sem necessidade de coleta de líquor. Caso 2: Lactente de seis meses que desenvolveu sintomas graves de liberação extrapiramidal relacionados à superdosagem de bromoprida, com reversão rápida dos sintomas após administração de biperideno. COMETÁRIOS: Este é o primeiro relato de distonia aguda após uso de bromoprida em crianças. Embora muito utilizada no Brasil como agente pró-cinético e antiemético, nenhum estudo clínico até o momento demonstrou melhor perfil de segurança da bromoprida em relação aos demais antieméticos antagonistas da dopamina. Até que tais estudos sejam realizados, sugere-se cautela na prescrição de bromoprida. Medidas não-farmacológicas devem ser recomendadas no tratamento de vômitos e da doença do refluxo gastresofágico. Quando o tratamento farmacológico for indispensável, deve-se dar preferência a drogas com perfil de segurança mais bem estabelecido.

OBJECTIVE: To report the case of two patients with acute dystonia induced by bromopride in children, followed by a review of the mechanisms of induction of movement disorders by antidopaminergic anti-emetic drugs, its clinical symptoms and treatment. CASE DESCRIPTION: Case 1: a 13 years old teenager who developed acute hypertonia and neck pain associated to fever and vomiting, suggestive of meningitis. Further investigation revealed that symptoms were associated with the ingestion of a single dose of bromopride. The symptoms stopped after administration of diphenidramine, preventing a spinal tap. Case 2: six months old infant who developed extrapyramidal movement disorder related to bromopride overdose, with prompt resolution of symptoms after treatment with biperiden. COMMENTS: This seems to be the first report of acute dystonia after the use of bromopride in children. Although frequently used in Brazil as an anti-emetic and prokynetic agent, no clinical study has showed that bromopride has a better safety profile than other antidopaminergic anti-emetic drugs. While such studies are not available, caution is needed in the context of pediatric prescription of bromopride. Non pharmacological measures should be adopted in the management of vomiting and gastroesophageal reflux. If medical treatment cannot be avoided, one would rather use medications with a better established safety profile.

Treatment of Parkinson's disease in Thailand: review of the literature and practical recommendations.

The mainstay of treatment for Parkinson's Disease (PD) remains symptomatic despite the rapid expansion in knowledge of its neurodegenerative process. Therapeutic options, both medical and surgical, have been markedly improved over the past decades, resulting in better motor function, activities of daily living, and quality of life for PD patients. The principle of PD management should be individualized and the selection of treatments should aim to control symptoms as well as to prevent or delay motor complications. In Thailand, various pharmacologic and surgical options are available, including different formulations of levodopa, dopamine agonists, monoamine oxidase B inhibitor, cathechol-O-methyltransferase inhibitor pallidotomy, and lastly deep brain stimulation. The use of dopamine agonists in early PD has a levodopa-sparing effect and reduces the incidence of motor complications. Continuous dopaminergic stimulation (CDS), which mimics physiological activation of dopaminergic receptors, has been proposed as a strategy to prevent motor complications. Based on current evidence, practical guidelines in the medical management of different types of motor complications are outlined in the present article according to what are available in Thailand. Surgical interventions should be reserved for patients with intractable motor complications after careful patient selection.

Effect of central microinjection of carbenoxolone in an experimental model of focal cerebral ischemia

Previous experimental studies have shown the protective effects of CBX on brain ischemic injures in global and in vitro models of ischemia. However, effects of CBX in temporary model of focal cerebral ischemia are not clear. Hence, the aim of this study was to investigate the effects of central micro injection of CBX on post-ischemic reperfusion injuries in a temporary model of focal cerebral ischemia. Transient focal cerebral ischemia was induced in rats by 60 min middle cerebral artery occlusion [MCAO], followed by 23 h reperfusion. CBX was administered into the right ventricle at doses of 1, 12, 25, 50 and/or 100 micro g/kg at the beginning of MCAO. Cortical and striatal infarct volumes and motor dysfunctions were assessed 24 h after MCAO. Administration of CBX at doses of 1, 12, 25 and/or 50 micro g/kg significantly reduced cortical infarct volumes by 35%, 49%, 41% and 43%, respectively [P<0.001]. In addition, CBX only at dose of 25 micro g/kg significantly reduced striatal infract volume and improved neurological dysfunctions [P<0.01]. Our findings indicated that central microinjection of CBX has protective effect on against ischemic reperfusion injuries in a transient model of focal cerebral ischemia

Efectividad de la ivermectina en un modelo de disquinesia tardía inducida por haloperidol en ratas / Effectiveness of ivermectin in rats with haloperidol induced tardive dyskinesia

Introducción: Los síntomas extrapiramidales y en especial las disquinesias tardías, son la mayor limitante de la terapia con antipsicóticos, debido a la frecuencia de aparición durante el tratamiento y la falta de recursos para controlar estas reacciones adversas, por lo cual es necesario investigar nuevos recursos para el manejo de las disquinesias tardías. Objetivo: Evaluar el efecto de la ivermectina sobre las disquinesias tardías inducidas por haloperidol en ratas. Métodos: En un modelo de dosis única de haloperidol con ratas Sprague Dawley, se evalúo la capacidad de la ivermectina para evitar cambios en la conducta motora y la aparición de movimientos anormales. Adicionalmente, se implementó un modelo animal crónico conocido como VCM (vacuous chewing movements), donde se evaluó la frecuencia de movimientos orofaciales durante seis meses, al recibir simultaneamente haloperidol e ivermectina a dosis diferentes, comparandolo con un grupo control y otro grupo al que se le administró haloperidol. Resultados: La ivermectina no evitó los cambios inducidos por haloperidol en el comportamiento motor, ni la aparición de movimientos anormales en el modelo agudo. Tampoco modificó la frecuencia de movimientos orofaciales en el modelo de administración crónica de haloperidol. La ivermectina no indujo cambios en la conducta motora, ni la aparición de movimientos anormales en los modelos agudo y crónico. Conclusiones: Los hallazgos de este trabajo descartan a la ivermectina como candidata para el manejo de las disquinesias tardías y no permite aportar argumentos a la hipótesis GABAérgica en la fisiopatología de las disquinesias tardías. Adicionalmente, la ivermectina no induce movimientos anormales.

Introduction: Extrapiramidal symptoms and tardive dyskinesia are common problems associated with antypsychotic therapy. Basic and clinical research is warranted due to the lack of effective therapies aimed to the prevention and treatment of antipsychotic side effects. Objective: To evaluate the effect of ivermectin in rats with haloperidol induced tardive dyskinesia. Methods: The effect of ivermectin on motor behavior and abnormal movements was tested in Sprague-Dawley rats treated with a single dose of haloperidol. In addition, a chronic animal model known as VCM (vacuous chewing movements) was implemented with the objective to evaluate the effect of ivermectin on the frequency of orofacial movements during a period of six months. Results: Ivermectin does not prevent the motor behavior and frequency of abnormal movements induced by haloperidol in the acute model. Orofacial movements were not reduced with ivermectin in the chronic model. In addition, ivermectin was not associated with changes in motor behavior and abnormal movements in the acute and chronic model. Conclusions: Ivermectin is not a good candidate for the treatment of tardive dyskinesia and the results of this study do not support the GABAergic hypothesis in the physiopathology of tardive dyskinesia. Additionally, ivermectin does not induce abnormal movements.

Use of clozapine in Brazilian patients with Parkinson's disease / Uso da clozapina em pacientes brasileiros com doença de Parkinson

Clozapine has been used as an attempt to manage levodopa complications in advanced Parkinson's disease (PD). To investigate the use of clozapine in this context in a Brazilian sample, a retrospective chart review was carried out at the Movement Disorders Clinic from the Federal University of Minas Gerais. This study enrolled 43 PD patients who used or were in use of clozapine. Patients had a mean age of 64 years and a mean UPDRS score of 55. Clozapine was indicated for dyskinesias in 17 patients, for psychosis in 15 and for both reasons in 11. The average maximum dose was 70 mg/day. Twenty six patients used it for a mean of 3.5 years. Twenty nine presented an improvement of their condition, 9 remained clinically stable. Twenty subjects interrupted the use of clozapine, being 9 due to adverse effects. Clozapine may play a role in the management of motor and psychiatric complications in PD, but it is associated with low tolerability.

A clozapina vem sendo utilizada na doença de Parkinson (DP) avançada para controle das complicações causadas pela levodopa. Com o objetivo de investigar o emprego da clozapina nesse contexto em amostra de pacientes brasileiros, um estudo retrospectivo foi realizado no Ambulatório de Distúrbios do Movimento da Universidade Federal de Minas Gerais. Este estudo incluiu 43 pacientes que usaram clozapina, apresentando idade média de 64 anos e uma média de 55 pontos no UPDRS. A clozapina foi indicada para discinesias em 17 pacientes, para psicose em 15 e para ambos os motivos em 11. A média da dose máxima empregada foi de cerca de 70 mg/dia. Vinte e seis pacientes usaram a medicação por uma média de 3,5 anos. Houve melhora do quadro clínico em 29 pacientes, 9 permaneceram com quadro clínico estático. O tratamento foi interrompido em 20 pessoas, sendo 9 por efeitos adversos. Apesar de a clozapina ser eficaz no controle das complicações motoras e psiquiátricas na DP, seu uso está associado com baixa tolerabilidade.

Behavioral effects of l-[m-chlorophenyl] piperazine [m-CPP] in a rat model of tardive dyskinesia

The present study was designed to monitor the responsiveness of 5-hydroxy tryptamine [5-HT]-2C receptor in rats treated with haloperidol exhibiting tardive dyskinesia [TD]. Results show that haloperidol injected at a dose of 1 mg/kg twice a day for two weeks elicited vacuous chewing movements [VCMs]. Which increased in a time dependent manner following the drug administration for 3-5 weeks. The behavioral effects of 1-[m-chlorophenyl]piperazine [m-CPP] a 5-HT-2C and 5-HT-1B agonist were monitored 2 days after 5 weeks of saline or haloperidol administration. The results show that hypophagic as well as anxiogenic-like effects of m-CPP are greater in repeated haloperidol than repeated saline injected animals, while hypolocomotive effects of m-CPP are not different in repeated saline and haloperidol injected animals. Results are discussed in the context of role of 5-HT-2C receptors in the regulation of the activity of dopaminergic neuron and its possible impact on elicitation of TD

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.

Comparative neurochemical changes associated with chronic administration of typical and atypical neuroleptics: implications in tardive dyskinesia.

An important goal of current neuroleptic research is to develop antipsychotic compounds with the low incidence of extrapyramidal side effects. The therapeutic success and less side-effect of atypical anti-psychotics such as clozapine and risperidone has focused the attention on the role of receptor systems other than dopaminergic system in the pathophysiology of neuroleptics-associated extrapyramidal side effects. The present study compares the effect of chronic administration of typical and atypical antipsychotics on neurochemical profile in rat forebrain. The study was planned to study changes in extracellular levels of norepinephrine, dopamine and serotonin in forebrain region of brain and tried to correlate them with hyperkinetic motor activities (vacuous chewing movements (VCM's), tongue protrusions and facial jerking) in rats, hall mark of chronic extrapyramidal side-effect of neuroleptic therapy tardive dyskinesia. Chronic administration of haloperidol (1 mg/kg) and chlorpromazine (5 mg/kg) resulted in significant increase in orofacial hyperkinetic movements where as clozapine and risperidone showed less significant increase in orofacial hyperkinetic movements as compared to control. There were also significant decrease in the extracellular levels of neurotransmitters dopamine, norepinephrine and serotonin in fore-brain as measured by HPLC/ED after chronic administration of haloperidol and chlorpromazine. Chronic administration of atypical neuroleptics clozapine and risperidone resulted in the decrease in extracellular concentration of dopamine and norepinephrine but the effect was less significant as compared to typical drugs. However, treatment with atypical neuroleptics resulted in 3 fold increase in serotonin levels as compared to forebrain of control rats. Typical and atypical neuroleptics showed varying effects on neurotransmitters, especially serotonin which may account for the difference in their profile of side effects (Tardive dyskinesia).

Relationship between tardive dyskinesia and the polymorphism of superoxide dismutase val9Ala and efficacy of Chaihu Taoren Capsules on it / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the relationship between efficacy of Chaihu Taoren Decoction (CTD) and the polymorphism of valine-alanine missense mutation of 9th codan (Val9Ala, T1183C) of superoxide dismutase (SOD) in patients with tardive dyskinesia (TD).</p><p><b>METHODS</b>Severity of TD was assessed by abnormal involuntary movement scale (AIMS), and the psychologic symptoms were rated by the positive and negative symptoms scale (PANSS). The sample size consisted of 119 patients with TD assigned to the TD group, 129 patients of chronic schizophrenia with the general condition matched strictly with that of the enrolled TD patients assigned to the non-TD group, and 148 healthy persons assigned to the normal group. The gene distribution rate of Val9Ala gene was analyzed using polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) analysis, and the therapeutic effect of CTD on 36 patients with TD was observed after 12 weeks treatment.</p><p><b>RESULTS</b>There was no significant difference in genotype and allelic gene frequency of SOD Val9Ala among the TD, non-TD and normal groups (P > 0.05). Comparison of the AIMS score in TD patients with various Val9Ala genotypes showed that the difference of AIMS scores in patients with TT and CT genotype was not significant (P > 0.05), but CTD did show a better efficacy in TD patients with CT heterozygote than in those with TT homozygote (P < 0.05).</p><p><b>CONCLUSION</b>The CTD could effectively relieve the symptoms of TD, its efficacy might be related with the genotype of SOD, and 9Ala is considered to be a protective factor for the susceptibility to TD.</p>

Neurochemical and behavioral effects of M-CPP in a rat model of tardive dyskinesia

Present study was designed to monitor the responsiveness of 5HT [5-Hydroxytryptamine] -2C receptors following the long-term administration of haloperidol in rats. Effects of m-CPP [meta-Chlorophenyl piperazine] were monitored 48h after withdrawal from repeated [twice a day for 5 week] administration of haloperidol [at the dose of 1mg/kg]. Vacuous chewing movements [VCMs] were monitored on weekly basis. Two days after withdrawal, animals were injected with saline [1ml/kg of body weight] or m-CPP [3mr/kg of body weight]. Activities in open field and light dark activity box were monitored 15 and 30 min post injection respectively. Animals were then decapitated [4h post injection] to collect dorsal striatum [DS] samples for the neurochemical analysis by HPLC-EC [High performance Liquid Chromatography with Electrochemical detection] method. Results from the present study showed significant hypolocomotive effect of m-CPP [p<0.05] in both repeated haloperidol as well as repeated saline injected rats. Neurochemical analysis of DS by HPLC-EC method showed that administration of m-CPP significantly [p<0.05] decreased 5-HIAA [5-Hydroxyindol acetic acid] in repeated haloperidol injected rats. In conclusion, present study provides evidence that 5HT-2C receptors become hypersensitive in a rat model of Tardive Dyskinesia [TD]. These findings have potential implication in the treatment of TD and attenuation of EPS induced by typical neuroleptics

Neuroleptic-induced tardive dyskinesia among Arab psychotic patients

We carried out a retrospective descriptive study to determine prevalence and risk factors for tardive dyskinesia [TD] among psychotic patients treated with conventional neuroleptics in 4 centres in Saudi Arabia. Records of patients who had been taking