Assessment of Drug-Associated Extrapyramidal Symptoms in People With Intellectual Disability: A Comparison of an Informant-Based Scale With Clinical Rating Scales.

Drug-associated extrapyramidal symptoms (EPS) in people with intellectual disability (ID) may be difficult to recognize, and clinicians' assessments may be hampered by lack of patients' capacities to adequately cooperate and by lack of reliable instruments to measure EPS in this population. Therefore, we compared assessments based on professional caregivers' observations with the informant-based validated Matson Evaluation of Drug Side Effects (MEDS) scale with assessments by clinicians using a set of clinical rating scales, most of which have not been validated for use in this population. We also compared 2 dyskinesia scales by replacing the widely used but not validated Abnormal Involuntary Movement Scale with the validated Dyskinesia Identification System Condensed User Scale (DISCUS) in half of the set of scales. We used linear regression to analyze associations between EPS as measured with MEDS and EPS as measured with the sets of scales at item and at scale level.Of the 30 MEDS items, 6 were associated with items of the other scales. At scale level, we found no significant associations. Comparison of the Abnormal Involuntary Movement Scale with the DISCUS indicated that the DISCUS may be preferable for use in people with ID.Results may be explained by shortcomings in education and training of caregivers and by lack of reliable assessments and rating scales for EPS in people with ID.We conclude that there is an urgent need for education and training of care professionals and clinicians in this area and for studies investigating the psychometric properties of rating scales.

The Addenbrooke's Cognitive Examination for the differential diagnosis and longitudinal assessment of patients with parkinsonian disorders.

OBJECTIVE: Differentiating idiopathic Parkinson's disease from atypical parkinsonian syndromes is challenging, especially in the early stages. We assessed whether the Revised Addenbrooke's Cognitive Examination (ACE-R) could differentiate between parkinsonian syndromes and reflect longitudinal changes in cognition in these disorders. METHODS: The ACE-R was administered at baseline and after approximately 18 months to 135 patients with parkinsonian disorders: 86 with idiopathic Parkinson's disease (PD), 30 with progressive supranuclear palsy (PSP), 19 with corticobasal degeneration (CBD). We assessed differences between groups for ACE-R, ACE-R subscores and Mini Mental State Examination (MMSE) scores at baseline (analyses of variance, receiver operating characteristics curves), and the interaction between diagnosis and change in ACE-R scores between visits (analyses of variance). RESULTS: The ACE-R verbal fluency subscore distinguished between PSP and PD with a high sensitivity (0.92) and specificity (0.87); total ACE-R score and the visuospatial subscore were less specific (0.87 and 0.84 respectively) and sensitive (0.70 and 0.73). Significant group level differences were found between PD and PSP for MMSE and ACE-R (total score and subscores for attention and concentration, fluency, language, and visuospatial function), and between PD and CBD for the ACE-R visuospatial subscore. Performance worsened between visits for ACE-R score in PD (p=0.001) and CBD (p=0.001); visuospatial subscore in PD (p=0.003), PSP (p=0.022) and CBD (p=0.0002); and MMSE in CBD (p=0.004). CONCLUSIONS: We propose the ACE-R, particularly the verbal fluency subscore, as a valuable contributor to the differential diagnosis of parkinsonian syndromes in the correct clinical context. The ACE-R may reflect disease progression in PD and CBD.

Preoperative localization of intracranial lesions with MRI using marking pills.

OBJECTIVE: To describe a simple technique for preoperative surface localization of intracranial lesions. METHODS: 11 pills in total, including Alfarol (alfacalcidol) capsules, were affixed to a phantom with adhesive tape and a MRI scan was performed. The visibility of the pills and any spatial errors in determining their locations were evaluated. Between June 2006 and April 2009, we employed Alfarol capsules as a skin marker in MRI in clinical surgical cases. RESULTS: Alfarol capsules, whose actual size is 5.6 mm in diameter, were identified as a hyperintense spot at a size of 4.2, 4.2, and 4.5mm in diameter in T1-weighted, T2-weighted, and FLAIR (fluid attenuated inversion recovery) sequence images, respectively. The size discrepancies were within 1.4 mm. The average spatial errors were 0.7, 0.6, and 0.7 mm in T1-weighted, T2-weighted, and FLAIR sequence images, respectively. Other pills were not identified in the MRI scans. During this 35-month period, 8 patients underwent preoperative MRI-guided localization at our institution. There were 5 men and 3 women in whom 8 biopsies were performed. In all cases, the result of the biopsy was positive and useful for the treatment that followed. No perioperative complications were encountered. CONCLUSION: Alfarol capsule can be used as an external skin marker. Our simple and inexpensive method is a useful addition to preoperative evaluation of superficial intracranial lesions.

Methodological issues in negative symptom trials.

Individuals from academia, the pharmaceutical industry, and the US Food and Drug Administration used a workshop format to discuss important methodological issues in the design of trials of pharmacological agents for improving negative symptoms in schizophrenia. The issues addressed included the need for a coprimary functional measure for registration trials; the characteristics of individuals who should enter negative symptom trials; the optimal duration for a proof-of-concept or registration trial; the optimal design of a study of a broad-spectrum agent that treats both positive and negative symptoms or a co-medication that is added to an antipsychotic; the relative strengths and weaknesses of available instruments for measuring negative symptoms; the definition of clinically meaningful improvement for these trials; and whether drugs can be approved for a subdomain of negative symptoms.

Assessment of adverse effects in clinical studies of antipsychotic medication: survey of methods used.

BACKGROUND: Clinical studies of antipsychotic medication are a primary source of data on the nature of, and relative liability for, adverse effects, relevant to prescribing decisions in clinical practice. AIMS: To identify how safety and tolerability data were collected and reported in recent clinical studies of antipsychotics. METHOD: A survey was conducted of all 167 eligible studies published between 2002 and 2007 on the Cochrane Schizophrenia Group register. RESULTS: Extrapyramidal side-effects (EPS) and weight gain were most frequently assessed. A minority of reports addressed metabolic abnormalities, aversive subjective experiences and sexual dysfunction. Published rating scales were frequently used to evaluate EPS, but systematic methods were rarely applied to other treatment-emergent problems. The definition of individual adverse effects and the manner of reporting were inconsistent. CONCLUSIONS: The way in which safety and tolerability data are collected and reported in clinical studies does not allow for fair and meaningful comparison of the relative risk profiles of individual antipsychotic drugs.

Cognitive and behavioral assessment in the early stages of neurodegenerative extrapyramidal syndromes.

Parkinson's disease (PD), Dementia with Lewy Bodies (DLB), Progressive Supranuclear Palsy (PSP) and Corticobasal Degeneration Syndrome (CBDS) are the most common neurodegenerative extrapyramidal syndromes. Beyond motor symptoms, cognitive dysfunctions and behavioral disturbances are reported. Neuropsychological and neuropsychiatry features in the early stages, however, are under-investigated, and few comparison studies are available yet. The aim of the present study was to evaluate the cognitive and behavioral profile in the early stages of neurodegenerative extrapyramidal syndromes. Thirty-nine PD, 27 DLB, 16 CBDS, and 24 PSP were recruited. Groups were matched for global cognitive and motor impairment. The overall sample showed a common neuropsychological core characterized by visuospatial deficits. Although in the early stage of the disease, a high presence of behavioral disturbances was detected, depression and anxiety were the most common disorders, followed by apathy and sleep disturbances. The observation of overlapping clinical entities points the attention on the need of adjunctive diagnostic markers for early differential diagnosis.

Cognitive and motor assessment in autopsy-proven corticobasal degeneration.

OBJECTIVE: To investigate the clinical features of autopsy-proven corticobasal degeneration (CBD). METHODS: We evaluated symptoms, signs, and neuropsychological deficits longitudinally in 15 patients with autopsy-proven CBD and related these observations directly to the neuroanatomic distribution of disease. RESULTS: At presentation, a specific pattern of cognitive impairment was evident, whereas an extrapyramidal motor abnormality was present in less than half of the patients. Follow-up examination revealed persistent impairment of apraxia and executive functioning, worsening language performance, and preserved memory. The motor disorder emerged and worsened as the condition progressed. Statistical analysis associated cognitive deficits with tau-immunoreactive pathology that is significantly more prominent in frontal and parietal cortices and the basal ganglia than temporal neocortex and the hippocampus. CONCLUSION: The clinical diagnosis of corticobasal degeneration should depend on a specific pattern of impaired cognition as well as an extrapyramidal motor disorder, reflecting the neuroanatomic distribution of disease in frontal and parietal cortices and the basal ganglia.

Primitive reflex evaluation in the clinical assessment of extrapyramidal syndromes.

The aim of the present study was to evaluate the role of primitive reflexes (PRs) as additional alert sign in routine clinical practice in patients with extrapyramidal syndrome. We considered glabellar, snout, palmomental and grasp reflexes in patients with mild stage of Lewy body dementia (LBD), corticobasal degeneration, progressive supranuclear palsy or Parkinson disease (PD). We also enrolled mild Alzheimer disease (AD) patients, and healthy subjects, as controls. LBD patients showed the highest prevalence of PRs compared with the other groups. The odds ratio of the risk of LBD in PRs > or = 2 was 27.9 (95% CI 2.9-269.0) compared with control group, 14.6 (95% CI 2.7-79.6) compared with mild AD, and 19.7 (95% CI 3.7-104.3) compared with PD. These data suggest that the occurrence of combination of PRs might be an useful additional warning sign of possible diffuse Lewy body pathology more than other causes of extrapyramidal syndrome.

Increased risk of extrapyramidal side-effect treatment associated with atypical antipsychotic polytherapy.

OBJECTIVE: To determine whether atypical antipsychotic polytherapy is a risk factor for drug treatment for extrapyramidal side-effects (anti-EPS drugs) and whether the risk is attributable to antipsychotic dose. METHOD: We studied Iowa Medicaid beneficiaries aged 18-64 years with an active atypical and no conventional antipsychotic on January 1, 2001. The association of atypical antipsychotic polytherapy with anti-EPS drug treatment was determined. Multiple logistic regression was utilized to adjust for covariates in two models, the first adjusting for age, sex and the specific antipsychotic(s) prescribed, and the second also adjusting for doses. RESULTS: Among 4400 patients, the unadjusted odds of anti-EPS treatment were increased two-fold with polytherapy. Polytherapy remained a risk factor in the first model (OR 1.5, 95% CI 1.1-2.0), but not after adjusting for doses (OR 1.0, 95% CI 0.7-1.4). CONCLUSION: Atypical antipsychotic polytherapy is a risk factor for anti-EPS drug treatment, apparently because of higher cumulative doses.

Defining and measuring clinical effectiveness in the treatment of schizophrenia.

OBJECTIVES: Expectations in treating schizophrenia are expanding beyond just controlling psychotic symptoms to include functional recovery. This report describes an approach to define and measure the clinical effectiveness of treatment in achieving these objectives. METHODS: A comprehensive literature review established that there is limited information about the meaning of the term "clinical effectiveness." To address this gap a consensus conference of schizophrenia researchers was held to consider the components of clinical effectiveness in real-world community practice and how these components can best be measured. RESULTS: The consensus of the researchers was that effective clinical treatment is characterized by four outcome domains: symptoms of disease, treatment burden, disease burden, and health and wellness. A clinical instrument to measure these four domains was constructed: Global Outcome Assessment of Life in Schizophrenia (GOALS). In using GOALS, clinicians rate each of the four domains on a scale of 1, very much improved, to 7, very much worse. Field-testing of this instrument is planned. CONCLUSIONS: Effective treatment interventions that combine optimal pharmacotherapy and targeted psychosocial treatments are raising expectations about the prospects of functional recovery among patients with schizophrenia. GOALS is proposed as one tool that can provide busy clinicians with a simple, objective measure of the effectiveness and outcomes of the clinical treatment they provide to patients with schizophrenia.

Interrater agreement in the assessment of motor manifestations of Huntington's disease.

With prospects improving for experimental therapeutics aimed at postponing the onset of illness in preclinical carriers of the Huntington's disease (HD) gene, we assessed agreement among experienced clinicians with respect to the motor manifestations of HD, a relevant outcome measure for preventive trials in this population. Seventy-five clinicians experienced in the evaluation of patients with early HD and six non-clinicians were shown a videotape compiled from the film archives of the United States-Venezuela Collaborative HD Research Project. Observers were asked to rate a 2-3-minute segment of the motor examination for each of 17 at-risk subjects. The rating scale ranged from 0 (normal) to 4 (unequivocal extrapyramidal movement disorder characteristic of HD). As measured by a weighted kappa statistic, there was substantial agreement among the 75 clinicians in the judgment of unequivocal motor abnormalities comparing scale ratings of 4 with ratings that were not 4 (weighted kappa = 0.67; standard error (SE) = 0.09). Agreement among the non-clinicians was only fair (weighted kappa = 0.28; SE = 0.10). Even under the artificial conditions of a videotape study, experienced clinicians show substantial agreement about the signs that constitute the motor manifestations of illness in subjects at risk for HD. We expect these findings to translate to a similar level of interobserver agreement in the clinical trial setting involving experienced investigators examining live patients.

Physical health monitoring of patients with schizophrenia.

OBJECTIVE: Schizophrenia is associated with several chronic physical illnesses and a shorter life expectancy, compared with life expectancy in the general population. One approach to improving the health of patients with schizophrenia is to improve the monitoring of physical health that occurs in psychiatric settings. The authors discuss a consensus panel's recommendations for improving the physical health monitoring of patients with schizophrenia who are treated in outpatient settings. METHOD: A consensus meeting including psychiatric and other medical experts assembled on October 17-18, 2002, to evaluate the existing literature and to develop recommendations for physical health monitoring of patients with schizophrenia. Conference participants reviewed the literature in the following areas: 1) weight gain and obesity; 2) diabetes; 3) hyperlipidemia; 4) prolongation of the QT interval on the ECG; 5) prolactin elevation and related sexual side effects; 6) extrapyramidal side effects, akathisia, and tardive dyskinesia; 7) cataracts; and 8) myocarditis. Experts for each topic area formulated monitoring recommendations that were discussed by all of the participants until a consensus was reached. RESULTS: Consensus recommendations included regular monitoring of body mass index, plasma glucose level, lipid profiles, and signs of prolactin elevation or sexual dysfunction. Information from monitoring should guide the selection of antipsychotic agents. Specific recommendations were made for cardiac monitoring of patients who receive medications associated with QT interval prolongation, including thioridazine, mesoridazine, and ziprasidone, and for monitoring for signs of myocarditis in patients treated with clozapine. Patients who receive both first- and second-generation antipsychotic medications should be examined for extrapyramidal symptoms and tardive dyskinesia. Patients with schizophrenia should receive regular visual examinations. CONCLUSIONS: The conference participants recommended that mental health care providers perform physical health monitoring that typically occurs in primary care settings for their patients who do not receive physical health monitoring in those settings. This change in usual practice is recommended on the basis of the conference participants' belief that this additional monitoring will result in the earlier detection of common, serious risk factors that could, without detection and intervention, contribute to impaired health of patients with schizophrenia.

[Instruments of depression assessment in schizophrenia]. / Instrumentos de evaluación de la depresión en la esquizofrenia1.

Lately, numerous reports have focused on the evaluation of depressive symptoms of schizophrenia. This assessment has been hampered by the temporal variability of the depressive symptoms and by their overlap with both the negative symptoms of schizophrenia and the extrapyramidal effects of the antipsychotic treatment. So far, classical assessment instruments such as the Hamilton Depression Rating Scale (HDRS) or the Montgomery-Asberg Rating Depression Scale (MARDS) have been used in those patients suffering from schizophrenia with depressive symptomatology, despite the important limitations concerning their use in subpopulations other than the one they have been developed for. New specific depression scales for schizophrenia such as the Calgary Depression Scale for Schizophrenics (CDSS) seems to have more efficiency and ability to distinguish between depression, negative and extrapyramidal symptoms. The present paper reviews the instruments used so far on the assessment of depressive symptomatology in schizophrenic patients.

Establishment of interrater reliability for a nursing Extrapyramidal Side Effects (EPS) Assessment Scale.

Many patients who receive antipsychotic medications experience dystonia, akinesia, dyskinesia, and akathisia, collectively called Extrapyramidal Symptom Side Effects (EPS). The purpose of this study was to establish interrater reliability for a Nursing EPS Assessment Scale developed to focus on all four symptom areas. Twenty RNs and 12 patients participated in the instrument development studies. After several revisions, interrater reliability significance was demonstrated at the 0.01 level. It was concluded that the Nursing EPS Assessment Scale possessed good interrater reliability for nursing assessment of EPS.

[Value of brain MR imaging in infants with a severe idiopathic apparent life threatening event]. / Apport pronostique de l'irm cerebrale chez les nourrissons rescapes d'un malaise grave.

OBJECTIVE: Prognostic value of a magnetic resonance imaging (MRI) scoring system in infants with a severe apparent life threatening event (ALTE). METHODS: Ten infants with an ALTE (aged between 6 and 31 weeks) were clinically graded according to the PRISM score and evaluated with EEG, evoked potentials and MRI. The 18 MRIs obtained were distributed in 3 classes according to the delay after which they were obtained; class A (n=5): within the first 48 hours after the event, class B (n=7): between day 3 and 8 and class C (n=6): between day 9 and 50. The 18 MRIs were evaluated retrospectively using a scoring system based on 3 categories of lesions: edema, basal ganglia injury and watershed injuries. Five infants died between day 2 and day 15 after the event. The five surviving infants had follow up neurodevelopmental testing after 38 to 77 months. RESULTS: There was no correlation between the 5 MRIs of class A and the neurological outcome. For the MRIs of class B and C, the scoring system can be of great value when combined with the scores of EEG, EP and PRISM. CONCLUSIONS: The scoring system for MRI performed within 48 hours after the event is falsely reassuring. MRI can be helpful as early as 3 days after the event when combined with the score of the electrophysiological investigations and the PRISM.

[Clinical and fine motor therapy assessment in Wilson disease]. / Klinische und feinmotorische Therapiekontrolle bei Morbus Wilson.

At the time of diagnosis and after therapy, we examined 33 patients suffering from Wilson's disease. We applied a standardized diagnostic score system on the basis of clinical signs. Without observing any differences between pseudoparkinsonian and pseudosclerosis subtypes, patients with neurological symptoms significantly improved by 2.33 points. Patients with initially more severe symptoms showed the same improvement as less affected patients. Fine motor disturbances were evaluated using the V-scope system. Finger tapping and drawing a spiral were compared to values of a healthy control group (n = 52). Patients with neurological symptoms showed significantly decreased frequencies in both tests. The clinical score was related to frequencies in finger tapping but not in drawing a spiral. Therefore finger tapping can be used as an objective diagnostic tool to evaluate the severity of Wilson's disease, while spiral testing appears to be a sensitive screening tool.

Masked assessment of MRI findings: is it possible to differentiate neuro-Behçet's disease from other central nervous system diseases? [corrected].

Two neuroradiologists reviewed MRI studies of 34 patients with neuro-Behcet's disease (NBD), 22 with multiple sclerosis (MS) and 7 with systemic lupus erythematosus (SLE) with central nervous system involvement, masked to the clinical diagnosis, age and sex of the patients. Of the patients with NBD 12 were in an acute attack; the others had chronic disease. MRI was assessed using a set of criteria, looking at atrophy, the site of discrete parenchymal lesions, regions of predominant involvement and the extent of the lesion(s). The observers also made a guess at the clinical diagnosis. The brain stem and/or basal ganglia were the most predominantly involved sites in all patients with acute NBD; 75% of these lesions were large and confluent, mainly extending from the brain stem to the diencephalon and basal ganglia. However, in chronic cases, the predominant involvement was in the brain stem and/or basal ganglia in only 36%, and in cerebral hemisphere white matter in another 36%; 27% of these patients showed no parenchymal lesion. Hemisphere white-matter lesions were equally distributed between periventricular and other areas in NBD, while in MS more were periventricular, and in SLE more were nonperiventricular. Brain-stem atrophy was seen in 21% of patients with NBD, with a specificity of 96.5%. In the absence of cortical atrophy, its specificity was 100%. The attempt at making a radiological diagnosis was successful in all cases of acute NBD and 95.5% of patients with MS, but in only 40% of patients with chronic NBD. Most of this latter groups MRI studies were interpreted as MS. An extensive lesion involving the brain stem and basal ganglia seemed to be diagnostic of acute NBD. However, hemisphere white-matter lesions could not be differentiated from those in MS.

Fluid-attenuated inversion recovery (FLAIR) for assessment of cerebral infarction. Initial clinical experience in 50 patients.

BACKGROUND AND PURPOSE: Our aim was to evaluate fluid-attenuated inversion recovery (FLAIR) sequence in the diagnosis of cerebral infarction with MRI. METHODS: A retrospective review was undertaken of 50 consecutive MRI studies ordered for suspected cerebrovascular accident. All studies included FLAIR and rapid acquisition with relaxation enhancement (RARE) T2-weighted spin-echo sequences. The two sequences were compared independently by four observers at two different institutions. Detectability of lesions and image quality were scored. RESULTS: Overall, FLAIR sequences proved superior in 10 patients, detecting acute cortical infarcts missed with RARE spin-echo technique in five patients. In five additional patients, improved characterization of chronic infarction and improved detection of microangiopathic deep hemispheric changes were observed. One brain stem infarct was missed with the FLAIR sequence. CONCLUSIONS: FLAIR offers advantages in detection of acute infarcts affecting the cortical ribbon, is a useful, rapid adjunct to conventional T2-weighted spin-echo sequences, and has the potential to replace these in the future.