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The two-stage evaluative process is an established framework utilized by forensic document examiners (FDEs) for reaching a conclusion about the source(s) of handwritten evidence. In the second, or discrimination, stage, the examiner attempts to estimate the rarity of observations in a relevant background population. Unfortunately, control samples from a relevant background population are often unavailable, leaving the FDE to reach this determination based on subjective experience. Automated handwriting feature recognition systems are capable of performing both feature comparison and discrimination, yet these systems have not been subjected to empirical validation studies. In the present study, we repurposed a commercially available automated system to generate empirical distributions for ranking feature dissimilarity scores among pairs of handwritten phrases. The blinded results of this automated process were used to survey an international cohort of 36 FDEs regarding their strength of support for same- and different-writer propositions. The survey served to cross-validate FDE decision-making under the two-stage approach. Results from the survey demonstrated a clear pattern of response consistent with ground truth. Predictive regression analyses indicated that the automated feature dissimilarity scores and the log of their cumulative distribution functions accounted for 72% of the variability in FDE opinions. This study demonstrated that feature dissimilarity scores acquired using automated processes and their distributions are closely aligned with FDE decision-making processes supporting the heuristic value of the two-stage evaluative framework.

Tardive dyskinesia (TD) is a movement disorder commonly associated with chronic exposure to antidopaminergic medications, which may be in some cases disfiguring and socially disabling. The consensus from a growing body of research on the incidence and prevalence of TD in the modern era of antipsychotics indicates that this disorder has not disappeared continues to challenge the effective management of psychotic symptoms in patients with schizophrenia. A fundamental component in an effective strategy for managing TD is its reliable and accurate assessment. In the present study, we examined the clinical utility of a brief handwriting dysfluency measure for quantifying TD. Digitized samples of handwritten circles and loops were obtained from 62 psychosis patients with or without TD and from 50 healthy subjects. Two measures of dysfluent pen movements were extracted from each vertical pen stroke, including normalized jerk and the number of acceleration peaks. Tardive dyskinesia patients exhibited significantly higher dysfluency scores than non-TD patients and controls. Severity of handwriting movement dysfluency was correlated with Abnormal Involuntary Movement Scale severity ratings for some tasks. The procedure yielded high degrees of test-retest reliability. These results suggest that measures of handwriting movement dysfluency may be particularly useful for objectively evaluating the efficacy of pharmacotherapeutic strategies for treating TD.

Ongoing monitoring of neuroleptic-induced extrapyramidal side effects (EPS) is important to maximize treatment outcome, improve medication adherence and reduce re-hospitalization. Traditional approaches for assessing EPS such as Parkinsonism, tardive akathisia, or dyskinesia rely upon clinical ratings. However, these observer-based EPS severity ratings can be unreliable and are subject to examiner bias. In contrast, quantitative instrumental methods are less subject to bias. Most instrumental methods have only limited clinical utility because of their complexity and costs. This paper describes an easy-to-use instrumental approach based on handwriting movements for quantifying EPS. Here, we present findings from psychiatric patients treated with atypical (second generation) antipsychotics. The handwriting task consisted of a sentence written several times within a 2 cm vertical boundary at a comfortable speed using an inkless pen and digitizing tablet. Kinematic variables including movement duration, peak vertical velocity and the number of acceleration peaks, and average normalized jerk (a measure of smoothness) for each up or down stroke and their submovements were analyzed. Results from 59 psychosis patients and 46 healthy comparison subjects revealed significant slowing and dysfluency in patients compared to controls. We observed differences across medications and daily dose. These findings support the ecological validity of handwriting movement analysis as an objective behavioral biomarker for quantifying the effects of antipsychotic medication and dose on the motor system.

Epidemiologic studies indicate that nearly 60% of schizophrenia (SZ) patients treated with conventional antipsychotic drugs develop extrapyramidal side effects (EPS) such as parkinsonism and tardive dyskinesia. Although the prevalence of EPS has decreased due to the newer antipsychotics, EPS continue to limit the effectiveness of these medicines. Ongoing monitoring of EPS is likely to improve treatment outcome or compliance and reduce the frequency of re-hospitalization. A quantitative analysis of handwriting kinematics was used to evaluate effects of antipsychotic medication type and dose in schizophrenia patients. Twenty-seven schizophrenia patients treated with risperidone, six schizophrenia patients who received no antipsychotic medication and 46 healthy comparison participants were enrolled. Participants performed a 20-minute handwriting task consisting of loops of various sizes and a sentence. Data were captured and analyzed using MovAlyzeR software. Results indicated that risperidone-treated participants exhibited significantly more dysfluent handwriting movements than either healthy or untreated SZ participants. Risperidone-treated participants exhibited lower movement velocities during production of simple loops compared to unmedicated patients. Handwriting dysfluency during sentence writing increased with dose. A 3-factor model consisting of kinematic variables derived from sentence writing accounted for 83% (r = .91) of the variability in medication dose. In contrast, we found no association between observer-based EPS severity ratings and medication dose. These findings support the importance of handwriting-based measures to monitor EPS in medicated schizophrenia patients.

Persistent neuroleptic-induced movement disorders limit effective pharmacological management of psychotic disorders. Although antipsychotic switching is a common strategy for managing extrapyramidal side effects (EPSs), there is insufficient empirical support to guide the clinician. We designed the present study to examine whether patients with preexisting EPS switched to quetiapine would show greater reduction in EPS compared with control patients.Twenty-two patients with schizophrenia meeting clinical criteria for tardive dyskinesia or coexisting parkinsonism were randomized either to switch from their current antipsychotic to quetiapine (n = 13) or to remain on their current treatment (n = 9). A battery of standard clinical assessments for EPS along with electromechanical instrumental measures was administered before randomization and again 1 and 3 months postrandomization.We observed significant reduction in parkinsonism (P0.001) and akathisia (P = 0.02) based on clinical assessments and dyskinesia (P0.05) based on instrumental assessment for the quetiapine group. Subjects remaining on current treatment exhibited an increase in rigidity (P0.05) based on instrumental measures.These findings support the switching to quetiapine in the management of preexisting neuroleptic-induced extrapyramidal side effects.

The accurate and objective measurement of abnormal, involuntary movements remains highly desirable, whether the movements are secondary to pharmacotherapy or an expression of the primary illness. In a previous study, we found that the prevalence of tardive dyskinesia in a sample of 100 subjects ranged from 28% when using the Abnormal Involuntary Movement Scale (AIMS) or the Dyskinesia Identification Scale, Condensed User Version (DISCUS) to 62% using an instrumental measurement (IM) of peripheral dyskinesia. The goal of this study was to examine the relationship between various risk factors for tardive dyskinesia as predictor variables, and the AIMS, DISCUS, and IMs of dyskinesia, tremor, and velocity of motor movement as dependent variables. The sample consisted of 100, mostly patients with schizophrenia. Poor performance on the Mini-Mental State Examination (MMSE) and increasing age were the most consistent predictors of dyskinetic and parkinsonian movements. Various predictors were associated with specific abnormal movements. Head injury was related to slower speed of motor movements and the total DISCUS score. A history of smoking was associated with less IM dyskinesia. For those with coexisting parkinsonism and dyskinesia, significant associations were found with head injury, diabetes mellitus, and an AIMS score of 2 or greater in 2 body areas. Various classes of psychotropic agents seemed to have little influence on the MMSE or the development of dyskinesia and parkinsonism. Increasing age and a lower score on the MMSE seem to be particularly helpful in gauging the risk for parkinsonian and dyskinetic movements.

The primary purpose of this study was to examine motor physiology disturbances in a group of patients with bipolar disorder by using sensitive instrumental procedures. The secondary aim of the study was to examine the effects of the affective state on motor functions. The authors studied 67 individuals meeting DSM-IV criteria for bipolar disorder and 47 healthy comparison subjects. Electromechanical measures of force steadiness and scaling of movement velocity to distance were performed. The authors found that performance on the force steadiness and velocity scaling measures was significantly poorer in the subjects with bipolar disorder, with 58% and 63% of the patients scoring outside the normal range on the force steadiness and velocity scaling measures, respectively. Eighty-four percent of subjects showed impairment on either measure, and 37% showed impairment on both measures. The force steadiness and velocity scaling abnormalities appeared to occur independently of one another and also were not associated with affective state or current medication status. This study demonstrates that motor abnormalities suggestive of basal ganglia dysfunction occur in many patients with bipolar disorder.

Individuals with bipolar disorder (BPD) exhibit motor, perceptual, and cognitive disturbances involving predominantly right hemisphere dysfunction. This asymmetry has been used to advance the hypothesis that the pathogenesis of bipolar disorder may be related to disturbances of the right cerebral hemisphere. We employed functional magnetic resonance imaging to examine hemispheric asymmetries in manic and depressed BPD. A secondary goal of the study was to examine effects of psychotropic medications on blood volume changes in the motor cortices.We studied 18 right-handed BPD and 13 right-handed normal healthy comparison subjects. Blood oxygen level dependent (BOLD) responses in the primary motor area (M1) and supplementary motor area (SMA) of both hemispheres were elicited during reaction time (RT) tasks.Healthy subjects activated the SMA in a reciprocal fashion with significantly greater activity in the left SMA for right hand trials and the right SMA for left hand trials. Depressed BPD subjects failed to show this normal reciprocity indicating a failure to suppress unwanted activity in the ipsilateral right SMA, whereas manic BPD subjects failed to suppress unwanted ipsilateral SMA activity in both hemispheres. Manic and depressed BPD subjects exhibited greater activity in the left primary motor area suggesting increased cortical excitability. BPD subjects treated with antipsychotics or mood-stabilizing medications exhibited longer RTs, lower BOLD responses in M1 and SMA, and a loss of normal hemispheric asymmetry in the SMA than untreated subjects.The presence of a right hemisphere disturbance in BPD is consistent with the hypothesis that the right hemisphere may be dominant in mood regulation. The presence of both left and right hemisphere disturbances in mania may explain the coexisting psychotic and affective symptoms observed in this condition.

We describe the results of a hand-held device for quantifying tremor in the upper extremity. The specific aims of the study were to evaluate: (1) the reliability of the device to record tremor frequency and amplitude; (2) the relationship between observer ratings of tremor severity and spectral power derived from the instrument; (3) the effects of limb posture on tremor properties recorded by the instrument; and (4) whether scores from the instrument can discriminate types of tremor with sufficient accuracy to be of diagnostic value. Results from 242 subjects with tremor showed significant effects of limb posture on tremor frequency detected by the device which could not be revealed using traditional observer severity ratings. Subjects with tremor associated with idiopathic Parkinson's disease were distinguished from patients with drug-induced parkinsonian tremor with 83% accuracy. These and other findings on instrument validity demonstrate that tremor assessment can be performed using standard quantitative procedures which overcome many of the limitations inherent in subjective observer ratings. The portability of this instrument, referred to as the Tremorometer, makes it a useful tool for multi-site collaborative studies in community settings.

Predicting response to antidepressant medication has been a challenge to clinicians and researchers for decades. Attention has been paid to the role of motor retardation as a putative indicator of treatment response, yet previous findings have been mixed. One reason for this inconsistency may be related to the subjective nature of motor retardation and how it is assessed. In the present study, we adopted a measure of motor programming previously shown to characterize parkinsonian bradykinesia to test whether neuromotor function could predict response to antidepressant treatment. Twenty-eight patients (14 males and 14 females with a mean age of 42.0 years) meeting DSM-IV criteria for a depressive disorder were randomized to receive 8 weeks of treatment with one of three antidepressant medications (sertraline, phenelzine, or bupropion). Treatment outcomes were assessed using the 17-item version of the Hamilton Rating Scale for Depression (HRSD). Patients were considered asymptomatic if their post-treatment HRSD total score was equal to or less than 7. Treatment responders (n=15) had significantly less baseline impairment (P=0.01) on the neuromotor measure than non-responders (n=13). There was a significant relationship between amount of improvement on the HRSD and severity of baseline neuromotor function (r=-0.51; P=0.006). No significant group effects were found for baseline psychomotor slowing or clinical ratings of motor retardation. These results demonstrate that a quantitative measure of motor programming may be a useful predictor of antidepressant non-response.

Predictors for the development of tardive dyskinesia (TD) have been studied extensively over the years, yet there are few studies of predictors of the course of TD after it has developed. Moreover, few studies have examined predictors of the course of other extrapyramidal side effects (EPS) in patients maintained on neuroleptics. The purpose of this study was to determine which modifiable variables are important in the prediction of EPS in patients with persistent TD over a period of as long as 2 years. One hundred fifty-eight patients enrolled in the Veterans Affairs Cooperative Study 394 were included in this study. A linear mixed-effects (LME) analysis to estimate the Abnormal Involuntary Movement Scale score (for TD severity), Simpson-Angus Scale (for parkinsonism severity), and Barnes Akathisia Scale at any given time after intake assessment was performed. The severity of each of the TD and EPS outcomes at any given visit was predicted by their respective baseline severity scores. Additional predictors of a favorable course of TD included lower doses of antipsychotic medications and use of anticholinergic medications. Other predictors of a favorable course of EPS included younger age and the use of atypical antipsychotic medication (for rigidity) and the use of anticholinergic medication (for tremor). These findings indicate that clinician-modifiable factors related to medication usage can influence the outcome of TD and EPS in patients with persistent TD.

An accumulating body of literature supports the notion that psychotic-like experiences (PLEs) may occur as a continuous phenotype. However, researchers are still working to determine if these events accompany an underlying continuum of neurobiological vulnerability as well. Within this context, it is notable that spontaneous dyskinetic movements are linked to specific pathogenic factors underlying schizophrenia, but to date there has been little research directed towards determining whether these events are associated with PLEs. In this study, 119 individuals were assessed for PLEs and administered with a sensitive instrumental test of upper extremity dyskinesia. Present findings suggest a relationship between subtle dyskinesia and PLEs in the general population, and provide a new perspective of the psychosis continuum by indicating that basal ganglia pathology may also underlie PLEs at the non-clinical end of this spectrum.

Objective To evaluate whether the relationship between extrapyramidal signs (EPS) and cognitive disturbances in Alzheimer's disease (AD) is influenced by illness duration. Methods A multivariate regression analysis was used to study the relationships between EPS, illness duration and five cognitive ability areas based on the Mattis Dementia Rating Scale (DRS) in 89 clinically diagnosed AD patients with extrapyramidal motor involvement. Results Severity of EPS was statistically associated with performance on four cognitive ability areas from the DRS including: attention, initiation and perseveration, construction and memory. Age was a significant factor related to severity of EPS. However illness duration did not contribute to the strength of the association between EPS and cognitive disturbances in patients with AD. Conclusions The findings of the present study support the notion that while neuropsychological and motor functions often coexist in patients with AD, their relationship seems to be unrelated to degenerative processes that accumulate throughout the illness. Copyright © 2001 John Wiley & Sons, Ltd.

Neurobehavioral disturbances often coexist with extrapyramidal signs (EPS) in patients with Alzheimer's disease (AD). In the present study, we examined the relationships between delusions and hallucinations and EPS by using standard observer ratings and sensitive electromyographic (EMG) measures in 52 patients with probable AD. On the basis of observer ratings, 36.5% of the patients exhibited psychotic features and 63.5% exhibited parkinsonism. Severity of clinically rated parkinsonism and the EMG measure of bradykinesia were significantly correlated with severity of neurobehavioral disturbances in this sample. The association between parkinsonism and delusions and hallucinations suggests a subcortical mechanism in the etiopathology of psychosis in AD.

In several retrospective post-mortem studies, patients meeting clinical criteria for Alzheimer's disease (AD) who gained the greatest cognitive benefit from treatment with an acetylcholinesterase (AChE) inhibitor were found to have neocortical Lewy bodies accompanying classical AD neuropathology. This 'dementia with Lewy bodies' (DLB) subtype manifests both parkinsonian and psychopathologic features that set it apart from 'pure' AD (hereafter called AD). In the present preliminary study, 16 dementia patients were prospectively categorized as having DLB versus AD. Subjects were also categorized according to their profile on surface electromyographic (EMG) measures demonstrated in prior work to be analogues of clinically observed parkinsonian extrapyramidal signs (EPS). All patients were prescribed the AChE inhibitor donepezil (5 mg per day). At baseline and at 6 months, patients underwent cognitive testing with the Mini-Mental State Examination (MMSE) while caregivers assessed their psychopathologic status using the Behavioral Symptoms in Alzheimer's Disease (BEHAVE-AD) scale. The tester was blinded to the AD versus DLB classification of the patients. AD cases (N=12) had only a slight increase in cognitive scores, while DLB patients' (N=4) mean MMSE scores increased to a significantly greater degree. Furthermore, patients categorized by EMG as EPS positive (N=8) attained an increase in their mean MMSE score from baseline to 6 months that differed significantly from a decline in MMSE observed among their EPS negative (N=4) counterparts. For all subjects, an increase in MMSE scores across 6 months of treatment correlated with a decline in BEHAVE-AD scores.

The study of motor slowness based on observational methods has limitations. Whether motor retardation has a psychomotor or neuromotor basis is unclear because psychiatric and motor symptoms overlap. Observational methods lack the precision necessary to distinguish cognitive from motor processes. For the present study, we used an objective measure of neuromotor dysfunction to quantify the extent to which an individual programs movement velocity in anticipation of increasing target distance. Persons with Parkinson's disease (PD) or functional psychosis were studied with a group of healthy comparison subjects. Results indicated that the slope of the linear function relating velocity to distance was abnormal in the PD group and in approximately half of the psychosis group. Analyses revealed the measure to have high specificity and sensitivity. Weak correlations between velocity scaling and psychopathology support the neuromotor basis of the measure. We conclude that this measure of velocity scaling is relatively uninfluenced by cognitive factors that may underlie psychomotor retardation.

Previous studies suggest that many untreated schizophrenia patients exhibit motor disturbances. On the basis of these findings, the authors hypothesized that preexisting extrapyramidal movement disorders may increase the risk of developing neuroleptic-induced parkinsonism (NIP). Thirty-five newly medicated psychotic patients underwent pretreatment clinical and instrumental motor and psychiatric assessments. Posttreatment ratings of parkinsonism were conducted at monthly intervals for the first 3 months and every 3 months thereafter. Thirteen patients (37%) developed NIP. Advanced age and pretreatment extrapyramidal disturbances predicted NIP. Life-table survival curves indicated that patients with pretreatment instrumental rigidity developed clinically significant NIP earlier than those without rigidity. These findings suggest that pretreatment motor dysfunction may be a risk factor for drug-induced parkinsonism, especially among older patients.

Nine VA Medical Centers are participating in a 2-year double-blind placebo controlled study of antioxidant treatment for tardive dyskinesia (TD) conducted by the Department of Veteran Affairs Cooperative Studies Program. One of the principal outcome measures of this study is the score derived from the instrumental assessment of upper extremity dyskinesia. Dyskinetic hand movements are quantified by assessing the variability associated with steady-state isometric force generated by the patient. In the present report, we describe the training procedures and results of a multi-center reliability assessment of this procedure. Data from nine study centers comprising 45 individual patients with six trials each (three from left hand and three from right hand) were reanalyzed by an independent investigator and the results were subjected to reliability assessment. For the statistic of interest (average coefficient of variation over trials 2 and 3 for each hand, then take the larger of these two values), we found very high intraclass correlation coefficients for reliability over all patients across sites (ICC = 0.995). We also calculated the reliability of the measures across trials within patient for each combination of hand (right, left, dominant), rater group (site, control), and trials set (all three, trials 2 and 3). For a given hand and trial set, the reliability of the site raters was similar to that of the control. This study demonstrates that instrumental measures for the assessment of dyskinesia are reliable and can be implemented in multi-center studies with minimal training.

Studies of extrapyramidal motor function in patients with schizophrenia have contributed to our understanding of the phenomenology and therapeutic outcome associated with neuroleptics. An increasing body of literature suggests that extrapyramidal motor abnormalities associated with schizophrenia may be linked to the pathophysiological mechanisms responsible for schizophrenia. Similarly, it has been documented that the extrapyramidal system may be involved in motor abnormalities in patients with Alzheimer's disease (AD). The present study was undertaken to examine motor function in schizophrenia and AD patients with psychosis. Quantitative instrumental procedures were used to examine rigidity, tremor, and bradykinesia in 13 neuroleptic-naive patients with schizophrenia, 13 AD patients with psychosis, and 26 age-comparable controls. Both schizophrenia and AD patients had significantly higher tremor and rigidity scores than did normal subjects. This comparative study of schizophrenia and AD patients with psychosis suggests that the effect of dementia in patients with psychosis is to prolong movement time, whereas abnormal parkinsonian postural tremor tends to be associated with psychosis in the absence of dementia.

It has been known for some time that patients with Parkinson's disease (PD) have difficulty executing simultaneous motor acts, yet the pathophysiology underlying this impairment remains uncertain. We examined the possibility that these dual-task deficits stem from defective sensorimotor mechanisms producing interference between the motor programs underlying the two tasks. Patients with PD and normal control subjects were tested on their ability to maintain steady-state force with one hand while performing a force-reaction time task with the other hand. Although performance was worse on the dual-task than on the single-task condition for both subject groups, only the patients with PD demonstrated significant interference between the two tasks. The interference across tasks improved in 87% of the patients with PD when tested after treatment with carbidopa/levodopa (Sinemet). These findings support the contention that, in patients with PD, disturbances in the execution of simultaneous motor performance may be due to sensorimotor disinhibition.

Fine control of isometric finger flexion force was measured to evaluate motor instability in 40 schizophrenic/schizoaffective patients exposed to neuroleptics and 43 age-comparable normal controls without prior neuroleptic exposure. All the subjects were free of idiopathic or neuroleptic-induced movement disorders. Older neuroleptic-treated patients exhibited significantly greater instability of isometric force compared with older controls, younger patients, or younger controls. Our study indicated that advanced age and neuroleptic exposure contributed to significantly greater motor instability than would be expected by advanced age or neuroleptic exposure alone. These findings are discussed as they pertain to potential mechanisms underlying neuroleptic-induced extrapyramidal side effects.

The authors examined severity of dyskinesia in 119 men and 44 women, comparing by gender those with late-onset schizophrenia (LOS) versus early-onset schizophrenia (EOS). Women with LOS and men with EOS had more severe dyskinesia than men with LOS and women with EOS. Many factors, including the length of neuroleptic treatment, alcohol and smoking history, and menopausal status, may contribute to the severity of dyskinesia in older patients with schizophrenia.

Rationale: Investigators have postulated that neuroleptic medications may affect the motor system through the creation of free radicals. Also, structural brain changes related to oxidative damage may disrupt normal striatal function. Objective: The goals of this study were to examine whether an antioxidant diet reduced the abnormal movements caused by long-term neuroleptic exposure and to examine structural effects within specific striatal regions in rats. Methods: Rats were given a basal diet or a diet high in antioxidants for 4 months, and treated with 10 mg/kg fluphenazine decanoate or sesame seed oil IM every 2 weeks. At baseline and after treatment, head movements were quantified by accelerometry, and immunocytochemically stained cholinergic neurons in the ventrolateral, mediodorsal, and ventromedial regions of the striatum were quantified. Results: Rats treated with fluphenazine had significantly lower neuron densities than those that did not receive antioxidants. Rats exposed to a diet consisting of antioxidants had significantly higher neuron densities than those that did not receive antioxidants in each of the three regions tested. Rats treated with fluphenazine had a greater increase in the number of accelerometric peaks recorded per minute compared with untreated animals. The increase in the number of accelerometric peaks recorded per minute was lower for animals exposed to antioxidant diets compared with unexposed animals. Lastly, there was a significant correlation between the accelerometric peak change score and cholinergic neuron density in all three regions. Conclusions: Our results suggest that long-term neuroleptic treatment is associated with an increase in head movements and a reduction in ChAT-stained striatal cholinergic neurons and that these abnormalities are reduced by antioxidants.

The need for objectivity in the assessment of parkinsonism prompted the development of a portable transducer capable of quantifying muscular rigidity. This paper describes the development and use of a device for measuring wrist rigidity and reports the preliminary findings from 25 normal healthy controls and 29 patients, many of whom were undergoing antiparkinsonian treatment to alleviate rigidity or antipsychotic treatment, which produced parkinsonian rigidity. An objective rigidity score, representing the degree to which motor activity increases muscular stiffness in the wrist, correlates highly with clinical ratings of parkinsonian rigidity and demonstrates 89% specificity and 82% sensitivity. Unlike previous techniques for quantifying rigidity, this transducer offers greater portability and apparent face validity.

The present study addressed the question of whether the emergence and severity of levodopa-induced dyskinesia was related to the therapeutic benefits derived from levodopa. Eight PD patients with clinically observed levodopa-induced dyskinesia were studied prior to and for two hours following a single dose of Sinemet (carbidopa/levodopa). Quantitative instrumental procedures were used to assess upper extremity dyskinesia, rigidity and bradykinesia. Results indicated that all patients exhibited significant reduction in their parkinsonism within 45 minutes following treatment. Reduction in bradykinesia, but not rigidity appeared to coincide with the emergence of dyskinesia. There was a significant relationship between severity of dyskinesia and the degree of improvement in movement velocity but not rigidity. Further analyses revealed that this relationship depended largely on the age of the patient. These findings are discussed as they pertain to a unified model of basal ganglia movement disorders which places dyskinesia and bradykinesia at opposite extremes along a continuum.

Background Several short-term, controlled trials have documented the efficacy of vitamin E in treating tardive dyskinesia. However, the persistent nature of the disease prompted us to perform a multicenter, longer-term trial of vitamin E. Methods The study was a prospective, randomized, 9-site trial of up to 2 years of treatment with d -vitamin E (1600 IU/d) vs matching placebo. One hundred fifty-eight subjects with tardive dyskinesia who were receiving neuroleptic medications were enrolled. The blinded assessments performed were clinical (Abnormal Involuntary Movements Scale, Barnes Akathisia Scale, and Modified Simpson-Angus [for Extrapyramidal Symptoms] Scale) and electromechanical assessments of movement disorders, psychiatric status (Brief Psychiatric Rating Scale), and functioning (Global Assessment of Functioning). There were no significant differences in baseline demographic characteristics or in study assessments between the group that received vitamin E and the group that received placebo. Results Vitamin E was well tolerated and subject compliance with medication was good and similar between treatment groups. One hundred seven subjects (70% of those receiving vitamin E and 66% of subjects receiving placebo) completed at least 1 year of treatment. There were no significant effects of vitamin E on total scores or subscale scores for the AIMS, electromechanical measures of dyskinesia, or scores from the other 4 scales. Conclusion This long-term, randomized trial of vitamin E vs placebo found no evidence for efficacy of vitamin E in the treatment of tardive dyskinesia.

Facial, trigeminal, and hypoglossal motoneuron involvement was quantified in 25 amyotrophic lateral sclerosis patients and in normal controls. Measures included (1) maximum voluntary contraction of the lower lip, mandible, and tongue using custom-designed force transducers, (2) clinical functions of each muscle group, and in some patients (3) orofacial mobility using videofluoroscopy. All measures indicated that the tongue muscles were most severely affected, even in patients who initially had symptoms in the extremities.

Interpreting central nervous system control of speech movement depends in part on understanding the detailed parameters of that movement. For example, the motor control significance of the often‐reported reflex responses elicited during speech depends upon whether the external eliciting stimuli generate mechanoreceptor activity that is comparable to that generated naturally by speech movements [cf., Caligiuri and Abbs, Society for Neurosciences (1984)]. Similarly, kinematic analyses of articulatory movement confined to average velocity without considering instantaneous velocity and acceleration are likely to be misleading insofar as the critical neuromotor actions are likely to be misinterpreted. For these reasons the labial dynamics for speech were investigated in five young adults. The maximum peak acceleration and velocity obtained during normal speech production were 544.9 cm/s2 and 39.7 cm/s, respectively, with means of 260.7 cm/s2 and 25.5 cm/s. Further analyses of the effects of increasing speaking...