Extrapyramidal Movement Disorders Research Articles

Oscillations as the Cause of Both Hyper- and Hypokinetic Symptoms of Movement Disorders

Back to table of contents Previous article Next article LETTERFull Accessβ Oscillations as the Cause of Both Hyper- and Hypokinetic Symptoms of Movement DisordersAlireza Akbari M.D.Shahriar Gharibzadeh M.D., Ph.D.,Alireza Akbari M.D.Search for more papers by this authorShahriar Gharibzadeh M.D., Ph.D.Search for more papers by this author,Published Online:1 Jul 2009https://doi.org/10.1176/jnp.2009.21.3.352AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Clinical manifestations of extrapyramidal movement disorders are usually divided into two main categories: hyperkinetic (i.e., tremor, athetosis, chorea, and ballism) and hypokinetic (i.e., akinesia, bradykinesia, and rigidity) symptoms. Despite the different pathological bases of these symptoms, simultaneous emersion of both kinds of symptoms in a single case (like coincidence of rigidity and tremor in a patient with Parkinson`s disease) and changing the general appearance of disease from hypo- or hyperkinesia to another group of symptoms suggests a similar origin for both groups of symptoms. With regard to the antikinetic effect of β band oscillatory activity, 1 all pathological procedures involving the basal ganglia can represent hypokinetic features if they persuade the basal ganglia network to oscillate at β band. Aggravation of hypokinesia caused by stimulation of subthalamic nucleus at 15 Hz through deep brain stimulation electrodes also supports the theory. 2 Simultaneous reduction of β band power and intensity of tremor during voluntary movements, 2 finding a roughly linear relationship between the amount of high frequency (at β band) synchronized activity and the patient’s tremor, and the fact that tremor cells are usually localized in the regions that also contain cells with a high frequency oscillatory component provide strong support for the role of β frequency in producing hyperkinetic symptoms. 3 Oscillation at β frequency is persistent and synchronized among large populations of neurons and caused by the alteration in network structure. Conversely, activity at tremor frequency is transient, synchronized just in small neuronal populations, and caused by the intrinsic membrane properties of neurons. 4 Therefore the tremor site will vary according to the site of the small neuronal assembly, which temporarily synchronizes at β frequency. Analyzing frequencies other than β band generated at some stage in movement disorders will help us improve our knowledge about how basal ganglia oscillatory activity transforms into hyperkinetic movements. We cannot discuss the oscillatory activities causing hyperkinesias in ballism and Huntington’s disease because chorea usually disappears with the induction of anesthesia; however, dystonia in L -dopa-induced dyskinesias is a hyperkinetic symptom that appears even under anesthesia and can be considered independent of cortical activity. Replacing the 4 Hz–7 Hz oscillatory activity seen in Parkinson’s disease with the 7 Hz–10 Hz seen in L -dopa-induced dyskinesias can change the hyperkinetic manifestation of disease from tremor to dystonia and offers a relationship between output frequencies of basal ganglia and hyperkinetic manifestations of disease. Although the peak at β band disappears in the power spectral density of subthalamic nucleus neurons affected by dopamine in L -dopa-induced dyskinesias, it is still present and can be recorded in the contralateral cortex. 5According to these observations we can conclude that neuronal synchronization at β band directly leads to the production of hypokinesia and creates a necessary background for hyperkinesia to emerge. Transient appearance of oscillatory activities in other frequencies can result in hyperkinetic movements only when they coincide with β band activity. Since the topography of motor cortex is preserved in the skeletomotor circuit, different sites of involuntary movements can be explained by different sites of oscillations in the basal ganglia.Neuromuscular Systems Laboratory, Amirkabir University of Technology, Tehran, Iran

β Oscillations as the Cause of Both Hyper- and Hypokinetic Symptoms of Movement Disorders

Back to table of contents Previous article Next article LETTERFull Accessβ Oscillations as the Cause of Both Hyper- and Hypokinetic Symptoms of Movement DisordersAlireza Akbari M.D.Shahriar Gharibzadeh M.D., Ph.D.,Alireza Akbari M.D.Search for more papers by this authorShahriar Gharibzadeh M.D., Ph.D.Search for more papers by this author,Published Online:1 Jul 2009https://doi.org/10.1176/jnp.2009.21.3.352AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Clinical manifestations of extrapyramidal movement disorders are usually divided into two main categories: hyperkinetic (i.e., tremor, athetosis, chorea, and ballism) and hypokinetic (i.e., akinesia, bradykinesia, and rigidity) symptoms. Despite the different pathological bases of these symptoms, simultaneous emersion of both kinds of symptoms in a single case (like coincidence of rigidity and tremor in a patient with Parkinson`s disease) and changing the general appearance of disease from hypo- or hyperkinesia to another group of symptoms suggests a similar origin for both groups of symptoms. With regard to the antikinetic effect of β band oscillatory activity, 1 all pathological procedures involving the basal ganglia can represent hypokinetic features if they persuade the basal ganglia network to oscillate at β band. Aggravation of hypokinesia caused by stimulation of subthalamic nucleus at 15 Hz through deep brain stimulation electrodes also supports the theory. 2 Simultaneous reduction of β band power and intensity of tremor during voluntary movements, 2 finding a roughly linear relationship between the amount of high frequency (at β band) synchronized activity and the patient’s tremor, and the fact that tremor cells are usually localized in the regions that also contain cells with a high frequency oscillatory component provide strong support for the role of β frequency in producing hyperkinetic symptoms. 3 Oscillation at β frequency is persistent and synchronized among large populations of neurons and caused by the alteration in network structure. Conversely, activity at tremor frequency is transient, synchronized just in small neuronal populations, and caused by the intrinsic membrane properties of neurons. 4 Therefore the tremor site will vary according to the site of the small neuronal assembly, which temporarily synchronizes at β frequency. Analyzing frequencies other than β band generated at some stage in movement disorders will help us improve our knowledge about how basal ganglia oscillatory activity transforms into hyperkinetic movements. We cannot discuss the oscillatory activities causing hyperkinesias in ballism and Huntington’s disease because chorea usually disappears with the induction of anesthesia; however, dystonia in L -dopa-induced dyskinesias is a hyperkinetic symptom that appears even under anesthesia and can be considered independent of cortical activity. Replacing the 4 Hz–7 Hz oscillatory activity seen in Parkinson’s disease with the 7 Hz–10 Hz seen in L -dopa-induced dyskinesias can change the hyperkinetic manifestation of disease from tremor to dystonia and offers a relationship between output frequencies of basal ganglia and hyperkinetic manifestations of disease. Although the peak at β band disappears in the power spectral density of subthalamic nucleus neurons affected by dopamine in L -dopa-induced dyskinesias, it is still present and can be recorded in the contralateral cortex. 5According to these observations we can conclude that neuronal synchronization at β band directly leads to the production of hypokinesia and creates a necessary background for hyperkinesia to emerge. Transient appearance of oscillatory activities in other frequencies can result in hyperkinetic movements only when they coincide with β band activity. Since the topography of motor cortex is preserved in the skeletomotor circuit, different sites of involuntary movements can be explained by different sites of oscillations in the basal ganglia.Neuromuscular Systems Laboratory, Amirkabir University of Technology, Tehran, Iran

Distonia aguda relacionada ao uso de bromoprida em pacientes pediátricos

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.

Neurotoxicity following chronic intravenous use of “Russian Cocktail”

Introduction. Recently, neurological abnormalities in methcathinone users have been attributed to manganese. We report similar toxicity in three patients following the use of a mixture similar to methcathinone: potassium permanganate, ephedrine, and aspirin. Case Reports. Three teenagers (15 to 19 years old) presented with extrapyramidal abnormalities and movement disorders following chronic intravenous use of a mixture known as “Russian Cocktail”. All three patients had multiple movement disorders. One patient had normal blood manganese concentration (<19 μg/L) and MRI. The other two had elevated blood manganese (2100 μg/L and 3176 μg/L) and MRIs showing bilateral symmetric hyper-intensities on T1-weighted-images in the dentate nucleus, subcortical white substance of cerebellar hemisphere, globus pallidus, and putamen. Abstinence and treatment with EDTA, levodopa, and para-aminosalicylic acid was associated with decreasing blood manganese concentrations and subjective improvement, but no change in objective findings. Discussion. The “Russian Cocktail” likely contains manganese as a result of the oxidation of ephedrine by potassium permanganate in water acidified by acetylsalicylic acid. We believe that manganese with the possible contribution of methcathinone caused the neurological impairments. Conclusions. Three toxic substances have been made into a mixture administered intravenously, similar to methcathinone. Our patients learned of this mixture, called “Russian Cocktail”, from their friends. The toxicity from repeated use of this mixture is one of extrapyramidal abnormalities and movement disorders. Standard therapies were unsuccessful in reversing the clinical toxicity.

Progabide in the treatment of hyperkinetic extrapyramidal movement disorders.

The ability of the selective GABA-receptor agonist, progabide, to suppress abnormal involuntary movements was evaluated in a preliminary open pilot study. 17 patients, 10 males and 7 females, aged 10-78 years, with hyperkinetic movement disorders were included in the study. Daily doses of progabide ranged from 900 to 3600 mg (median 2400 mg) corresponding to 14-45 mg/kg (median 45 mg/kg), while the duration of treatment varied from 2 to 52 weeks. Improvement, with a reduction of involuntary movements exceeding 25%, occurred in two of four patients with Gilles de la Tourette's syndrome, and in two of three patients with postanoxic intention myoclonus, while no consistent beneficial effects were registered in ten patients with Huntington's chorea, postanoxic choreoathetosis, torsion dystonia, tardive dyskinesia, action tremor, essential myoclonus, or oro-branchio-respiratory myoclonus.

Activation of striatal inflammatory mediators and caspase-3 is central to haloperidol-induced orofacial dyskinesia

The undesired extrapyramidal movement disorders observed with long term treatment with haloperidol have been associated with striatal neurodegeneration. The present study was designed to investigate the effect of prolonged haloperidol treatment on striatal levels of inflammatory mediators and caspase-3 and to correlate it with orofacial dyskinesia, a movement disorder observed with long term haloperidol treatment. Prolonged administration of haloperidol (1, 2, 5 mg/kg) to rats produced dose-dependent increase in the orofacial dyskinetic movements and induced a marked oxidative stress in the striatum. Lower dose of haloperidol (1 mg/kg) decreased NO levels but did not induce TNF-α or NF-κB expression. At higher doses (2 and 5 mg/kg), increased levels of total nitric oxide and TNF-α in cytoplasmic lysate and active p65 subunit of NF-κB in nuclear lysates of rat brain were observed. These doses (2 and 5 mg/kg) also induced an increased expression of caspase-3 protein in striatal cytoplasmic fraction as shown by western blot analysis. Collectively, we conclude that oxidative stress mediated increase in inflammatory mediators may initiate the apoptotic pathway (caspase-3) after chronic haloperidol treatment. All this is well correlated with behavioural development of orofacial dyskinesia.

CARDIAC MANIFESTATIONS IN A CHILD WITH A NOVEL MUTATION IN CREATINE TRANSPORTER GENE SLC6A8

The creatine-phosphocreatine shuttle serves to maintain a high-energy phosphate supply for normal cellular function. Most creatine is derived from the diet; the rest is synthesized primarily in the liver, pancreas, and kidneys. The transport of creatine in tissues is accomplished by the Na+-dependent transporter SLC6A8. Expression of the SLC6A8 gene is high in skeletal muscle, heart, and kidney, moderate in brain, and extremely low in liver and pancreas. X-linked creatine transporter (Crt) defect (OMIM 300352), originally described in 2001,1 has been linked to mutations in the SL6CA8 gene at Xq28. SLC6A8 deficiency may comprise up to 1% of cases of mental retardation of unknown etiology in males.2 Intellectual disability is the uniform feature in patients with creatine-deficiency syndromes.3,4 Some patients also have epilepsy, extrapyramidal movement disorder, failure to thrive, and sometimes autism and other behavioral problems.4 We report a novel mutation in the SLC6A8 gene in an 11-year-old boy with Crt defect, who presented with multiple premature ventricular contractions (PVCs) in the second year of life. ### Case report. This male child had poor weight gain since birth. By 18 months of age his weight dropped below the fifth percentile and he was admitted for investigation. When given midazolam IV and topical lidocaine before an endoscopy, he immediately developed frequent PVCs (bigeminy …

Autosomal recessive GTP cyclohydrolase I deficiency without hyperphenylalaninemia: Evidence of a phenotypic continuum between dominant and recessive forms

We describe a unique presentation of autosomal recessive (AR) GTP cyclohydrolase I (GTPCH) deficiency, with severe CNS involvement but without hyperphenylalaninemia. A male infant presented with progressive spasticity, dystonia and oculogyric episodes. Blood phenylalanine levels were persistently normal: whereas an oral phenylalanine loading test revealed impaired phenylalanine clearance. CSF neopterin and tetrahydrobiopterin (BH 4) were low, homovanillic acid marginally low and 5-hydroxyindoleacetic acid normal. Fibroblasts showed decreased GTPCH enzyme activity. A homozygous novel mutation of GCH1, p.V206A, was identified. On treatment (BH 4, l-Dopa/Carbidopa and 5-hydroxytryptophan), motor development improved. Mutational analysis provided neonatal diagnosis of a younger brother who, after 18 months on treatment, shows normal development. AR GTPCH I deficiency can present without hyperphenylalaninemia and with normal or subtle CSF neurotransmitter profiles. Testing for GTPCH deficiency should be considered for patients with unexplained neurological symptoms and extrapyramidal movement disorder.

Tourette's syndrome: clinical features, pathophysiology, and therapeutic approaches.

Tourette's syndrome (TS) is a disorder characterized by simple and complex motor tics, vocal tics, and frequently obsessive-compulsive symptoms. Its onset occurs before the age of 21. Typically, TS shows a waxing and waning course, but a chronification of the tics, even during later life, is often observed. TS mainly occurs in boys, and shows genetic heritability with differing penetrance. The pathological mechanism is still unclear Neuroanatomical and neuroimaging studies, as well as effective treatment using antipsychotics, suggest that a disturbance of the dopaminergic system in the basal ganglia plays an important role in the pathogenesis of TS. Several possibly causative mechanisms of the disturbed dopaminergic neurotransmission are discussed, with the main emphasis on the-infection-triggered-inflammatory immune process. Extrapyramidal movement disorders are known to occur as a symptom of poststreptococcal disease, such as in Sydenham's chorea. Cases of childhood TS are proposed to be caused by such a poststreptococcal mechanism, being part of a spectrum of childhood neurobehavioral disorders termed pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS). The overlap between TS and PANDAS is discussed, and a critical view of the PANDAS concept is presented. The therapeutic implications of the different pathological mechanisms are described, taking into consideration not only the acute or chronic natures of different infections, but also an autoimmune process. Moreover, therapeutic strategies using typical and atypical antipsychotics, and also experimental therapies such as repetitive transcranial magnetic stimulation and deep brain stimulation, are critically discussed.

Effect of spirulina maxima on the haloperidol induced tardive dyskinesia and oxidative stress in rats

Haloperidol is a widely used neuroleptic drug for the treatment of acute and chronic psychosis. The use of haloperidol is limited by extrapyramidal movement disorders such as Parkinsonism, akathesia, dystonia, and tardive dyskinesia (TD). Treatment with haloperidol increases oxyradicals which are implicated in TD. Spirulina is widely used as nutritional supplement rich in proteins and antioxidants. The present study is proposed to study the effect of spirulina on haloperidol induced TD and oxidative stress by studying TD, various enzymatic and nonenzymatic antioxidants and lipid peroxidation. Haloperidol 1 mg/kg/i.p was used to induce vacuous chewing movements in rats. Spirulina maxima suspended in 1% between 80 at a dose of 45, 90 and 180 mg/kg were administered by gavage along with haloperidol from 21st day to 49th day of treatment. Spirulina supplementation at a dose of 180 mg/kg significantly improved enzymatic and nonenzymatic antioxidants and decreased the tardive dyskinesia induced by haloperidol. In conclusion, the results of present investigation suggest that spirulina decreases haloperidol induced oxidative stress and TD by many mechanisms as it is cocktail of antioxidants. On chronic use it may inhibit haloperidol induced reduced expression of DNA thereby increases the expression of enzymatic and nonenzymatic antioxidants and protects against oxidative stress induced neurodegeneration and TD.

Acute Chorea with Bilateral Basal Ganglia Lesions in Diabetic Uremia

Uremia is a syndrome of clinical and metabolic abnormalities, which develops in parallel with the deterioration of renal function. Uremic encephalopathy is one of many manifestations of acute or chronic renal failure. It is usually applied to patients with cortical involvement, such as confusion, seizure, tremor, myoclonus, or asterixis. Some cases of acute extrapyramidal movement disorders associated with bilateral basal ganglia lesions, especially parkinsonism have been reported in uremic patients. Here, we report a diabetic uremic patient who developed acute chorea associated with bilateral basal ganglia lesions.

Treatment of symptomatic heterozygous aceruloplasminemia with oral zinc sulphate

Aceruloplasminemia is an autosomal recessive and phenotypically primarily neurodegenerative disease caused by a homozygous mutation of the ceruloplasmin gene. The absence of ceruloplasmin and its ferroxidase activity leads to pathological iron overload in the brain and other organs. While heterozygous carriers of ceruloplasmin gene mutations have been believed to be asymptomatic, a number of cases with neurological deficits have recently been described. To date, an effective treatment has not been established for either aceruloplasminemia or symptomatic heterozygous aceruloplasminemia. The present report concerns the beneficial treatment of an 18-year-old girl with extrapyramidal and cerebellar-mediated movement disorder caused by a heterozygous mutation of the ceruloplasmin gene using oral zinc sulphate.

Effects of haloperidol and its pyridinium metabolite on plasma membrane permeability and fluidity in the rat brain

The use of antipsychotic drugs is limited by their tendency to produce extrapyramidal movement disorders such as tardive dyskinesia and parkinsonism. In previous reports it was speculated that extrapyramidal side effects associated with the butyrophenone neuroleptic agent haloperidol (HP) could be caused in part by the neurotoxic effect of its pyridinium metabolite (HPP +). Although both HPP + and HP have been shown to induce neurotoxic effects such as loss of cell membrane integrity, no information exists about the difference in the neurotoxic potency, especially in the potency to induce plasma membrane damage, between these two agents. In the present study, we compared the potency of the interaction of HPP + and HP with the plasma membrane integrity in the rat brain. Membrane permeabilization (assessed as [ 18 F]2-fluoro-2-deoxy- d-glucose-6-phosphate release from brain slices) and fluidization (assessed as the reduction in the plasma membrane anisotropy of 1,6-diphenyl 1,3,5-hexatriene) were induced by HPP + loading (at ≥ 100 μM and ≥ 10 μM, respectively), while comparable changes were induced only at a higher concentration of HP (= 1 mM). These results suggest that HPP + has a higher potency to induce plasma membrane damage than HP, and these actions of HPP + may partly underlie the pathogenesis of HP-induced extrapyramidal side effects.

Video of dantrolene effectiveness on neuroleptic malignant syndrome associated muscular rigidity and tremor

Neuroleptic malignant syndrome (NMS) is an uncommon but potentially fatal adverse reaction to neuroleptic drugs, including amisulpride [1,2]. NMS most commonly presents with increased body temperature, muscular rigidity of a ‘lead pipe’ nature, altered mental status and autonomic dysfunction. Other extrapyramidal movement disorders such as tremor and cogwheel phenomena are also frequently present. The treatment of NMS includes discontinuation of contributing drugs and supportive therapy, but specific treatment with dantrolene, bromocriptine, nondepolarizing neuromuscular paralysis and benzodiazepines, among other such agents, has been reported only anecdotally. A recent analysis of published case reports [3] evaluated the efficacy of dantrolene in NMS; it found that dantrolene, given as monotherapy, might be helpful in managing this syndrome if the premedication was a neuroleptic monotherapy. We present video evidence of the effectiveness of dantrolene in reducing muscular rigidity,

Atypical Onset of Symptoms in Huntington Disease: Severe Cognitive Decline Preceding Chorea or Other Motor Manifestations

To describe the onset of Huntington disease (HD) in a patient with atypical progression of symptoms. The authors report the case of a 39-year-old man with severe cognitive impairment and diffuse cortical atrophy before the onset of motor manifestations or symptoms of an extrapyramidal movement disorder. Clinical examinations, neuropsychologic assessments, magnetic resonance imaging, electroencephalogram, and genetic testing were conducted. Although HD was eventually confirmed through genetic testing, chorea was not part of the clinical picture until well after the patient had developed a frank dementia, with a decline in global intellectual functioning, memory deficits, slowed information processing speed, and executive dysfunction. This case indicates HD may present with atypical clinical features in the early course of the disease, and warrants diagnostic consideration in patients with early dementia of unknown etiology.

High frequency of creatine deficiency syndromes in patients with unexplained mental retardation

Cerebral creatine deficiency syndromes (CCDSs) are inborn errors of metabolism that include two autosomal recessive creatine biosynthesis defects (arginine–glycine amidinotransferase [AGAT; OMIM 602360] and guanidinoacetate methyl transferase [GAMT; OMIM 601240] deficiency) and an X-linked creatine transporter defect (OMIM 300036).1 The clinical phenotype is variable, associating nonspecific mental retardation, epilepsy, extrapyramidal movement disorders, and autistic behavior. The frequency of CCDS is unknown and probably underestimated. We report a high frequency of CCDS in mentally retarded children, mostly boys with an X-linked creatine transporter deficiency. Over a period of18 months, children referred to the Department of Pediatric Neurology with unexplained mild to severe mental retardation, normal karyotype, and absence of fragile X syndrome were prospectively screened for CCDS. Children were from diverse ethnic backgrounds. Children with polymalformative syndromes were excluded. Creatinine metabolism was evaluated using creatine/creatinine and guanidinoacetate (GAA)/creatinine ratios on a spot urine.2 Diagnosis was further confirmed using brain proton MR spectroscopy (H-MRS) and …

Reduction in psychotic symptoms as a predictor of patient satisfaction with antipsychotic medication in schizophrenia: Data from a randomized double-blind trial

BackgroundPatient satisfaction with antipsychotic treatment is important. Limited evidence suggests that satisfaction is associated with symptom improvement and compliance. Predictors of patient satisfaction with antipsychotic medication were examined in a study of patients with a recent exacerbation of schizophrenia.MethodsData are from a randomized, double-blind trial comparing risperidone (n = 152), quetiapine (n = 156), and placebo (n = 73). Medication Satisfaction Questionnaire (MSQ) was completed after 14 days of treatment and after 6 weeks at last study visit.ResultsMedication satisfaction at both time points was significantly associated in multiple regression analysis with improvement on 3 Positive and Negative Syndrome Scale (PANSS) factor scores (positive symptoms p < .01; uncontrolled hostility/excitement, p < .0005; anxiety/depression, p < .04) and treatment with risperidone (p < .03); at day 14, significant association was also found with older age (p = .01). At both time points, predictor variables explained over 30% of the variance in medication satisfaction. Change in Hamilton Depression Scale, prolactin levels, sex, and reported adverse events of extrapyramidal symptoms, sedation, and movement disorders were not significant predictors of satisfaction. Lower level of medication satisfaction at day 14 was associated with earlier discontinuation in the trial at week 6 end point. A focused principal components analysis of PANSS factors and MSQ suggested that medication satisfaction relates to 3 groups of factors in descending order of magnitude: lower levels of (a) uncontrolled hostility/excitement, (b) positive symptoms, and (c) negative symptoms, disorganized thoughts, and anxiety/depression.ConclusionResults give further support that treatment satisfaction is positively associated with symptom improvement, particularly psychotic symptoms, and suggest that satisfaction may also be related to compliance, as those who were more satisfied remained in the trial for a longer period of time.Trial registration numberTrial registration number NCT00061802

Tardive Dyskinesia Circa 2006

Tardive Dyskinesia Circa 2006

X‐linked creatine transporter defect: A report on two unrelated boys with a severe clinical phenotype

We report two unrelated boys with the X-linked creatine transporter defect (CRTR) and clinical features more severe than those previously described with this disorder. These two boys presented at ages 12 and 30 months with severe mental retardation, absent speech development, hypotonia, myopathy and extra-pyramidal movement disorder. One boy has seizures and some dysmorphic features; he also has evidence of an oxidative phosphorylation defect. They both had classical absence of creatine peak on brain magnetic resonance spectroscopy (MRS). In one, however, this critical finding was overlooked in the initial interpretation and was discovered upon subsequent review of the MRS. Molecular studies showed large genomic deletions of a large part of the 3' end of the complete open reading frame of the SLC6A8 gene. This report emphasizes the importance of MRS in evaluating neurological symptoms, broadens the phenotypic spectrum of CRTR and adds knowledge about the pathogenesis of creatine depletion in the brain and retina.

Extrapyramidal Movement Disorders Induced by Metoclopramide (About 7 Cases)

Extrapyramidal Movement Disorders Induced by Metoclopramide (About 7 Cases)