Resveratrol Protects Against Vacuous Chewing Movements Induced by Chronic Treatment with Fluphenazine.

Typical antipsychotics, which are commonly used to treat schizophrenia, cause motor disorders such as tardive dyskinesia (TD) in humans and orofacial dyskinesia (OD) in rodents. The disease mechanisms as well as treatment effectiveness are still unknown. In this study, we investigated the effect of resveratrol, a polyphenol with neuroprotective properties, on behavioral changes induced by chronic treatment with fluphenazine in rats and the possible relationship between monoamine oxidase (MAO) activity and vacuous chewing movements (VCMs). Rats were treated for 18 weeks with fluphenazine enantate [25 mg/kg, intramuscularly (i.m.), every 21 days] and/or resveratrol (20 mg/kg, offered daily in drinking water). Next, body weight gain, behavioral parameters (VCMs and open field tests-locomotor and rearing activity), and MAO activity were evaluated. Fluphenazine treatment reduced body weight gain, number of crossings and rearings, and the co-treatment with resveratrol did not affect these alterations. Fluphenazine increased the prevalence and intensity of VCMs and the co-treatment with resveratrol reduced the VCMs. Furthermore, a negative correlation was found between the number of VCMs and MAO-B activity in the striatum of rats. Our data suggest that resveratrol could be promissory to decrease OD. Moreover, MAO-B activity in the striatum seems to be related to VCMs intensity.

Young adults with dyskinetic cerebral palsy improve subjectively on pallidal stimulation, but not in formal dystonia, gait, speech and swallowing testing.

BACKGROUND: Pharmacological treatment of dyskinetic cerebral palsy (CP) is often ineffective. Data about outcome of deep brain stimulation (DBS) in these patients remains scarce. METHODS: Eight patients with dyskinetic CP and DBS of the Globus Pallidus internus were investigated. Using pre- and postoperative videos the severity of dystonia and changes thereof during standardized settings ('on') and after the stimulator had been switched off ('off') were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). Furthermore, subjective impression (SI) of the extent of postoperative change as well as gait (Leonardo Mechanograph® Gangway), speech (Frenchay Dysarthria) and swallowing performances (fiberoptic laryngoscopy) were assessed during 'on' and 'off'. RESULTS: When comparing pre- and postoperative as well as 'on' and 'off', the BFMDRS and most of the gait, speech, and swallowing parameters did not differ significantly. In contrast, patients reported significant improvement of their SI postoperatively (3.1 on a 10-point-scale). CONCLUSION: Data show that our CP-patients did not benefit from GPi-DBS when tested formally for dystonia, gait, speech and swallowing. In stark contrast, these patients reported significant subjective improvement. Taken together, and in light of current unsatisfactory medical treatment options, our data suggest that further assessment of the effects of GPi-DBS in dyskinetic CP is warranted.

[Movement disorders is psychiatric diseases]. / Mozgászavarok pszichiátriai betegségekben.

Movement disorders are common in psychiatry. The movement disorder can either be the symptom of a psychiatric disorder, can share a common aetiological factor with it, or can be the consequence of psychopharmacological therapy. Most common features include tic, stereotypy, compulsion, akathisia, dyskinesias, tremor, hypokinesia and disturbances of posture and gait. We discuss characteristics and clinical importance of these features. Movement disorders are frequently present in mood disorders, anxiety disorders, schizophrenia, catatonia, Tourette-disorder and psychogenic movement disorder, leading to differential-diagnostic and therapeutical difficulties in everyday practice. Movement disorders due to psychopharmacotherapy can be classified as early-onset, late-onset and tardive. Frequent psychiatric comorbidity is found in primary movement disorders, such as Parkinson's disease, Wilson's disease, Huntington's disease, diffuse Lewy-body disorder. Complex neuropsychiatric approach is effective concerning overlapping clinical features and spectrums of disorders in terms of movement disorders and psychiatric diseases.

Parent-reported participation in children with cerebral palsy: the contribution of recurrent musculoskeletal pain and child mental health problems.

AIM: The aim of the study was to explore the contribution of recurrent musculoskeletal pain and mental health to aspects of participation in children with cerebral palsy (CP). METHOD: A total of 105 participants (54 males, 51 females); mean age 14 y (SD 3) were assessed by clinical examination, interview, and parental questionnaires. CP type distribution was as follows: spastic unilateral, 37%; spastic bilateral, 56%; and dyskinetic, 7%. Motor function assessed using the Gross Motor Function Classification System was level I, 33%; level II, 40%; level III, 15%; and level IV/V, 11%. Parents reported child participation using the Assessment of Life Habits, child mental health problems using the Strengths and Difficulties Questionnaire, their own mental health using the General Health Questionnaire, and their socioeconomic status. RESULTS: Recurrent musculoskeletal pain was associated with reduced accomplishment of daily activities (B=-1.22, p=0.02) and social roles (B=-1.17, p=0.03), and with reduced parental satisfaction with the accomplishment of daily activities (B=-1.14, p=0.03) and social roles (B=-1.48, p<0.01). Increasing levels of child mental health problems was associated with reduced accomplishment of daily activities (B=-0.10, p=0.02) and social roles (B=-0.11, p<0.01), and with reduced parental satisfaction with the accomplishment of social roles (B=-0.21, p<0.01). INTERPRETATION: Pain and child mental health should be considered in most participation models in CP. Regarding participation as an objective outcome measure is questionable.

[Anti-NMDA receptor encephalitis: a neurological and psychiatric emergency]. / Anti-NMDA-Rezeptor-Enzephalitis: Ein neurologisch-psychiatrischer Notfall.

Anti-NMDA receptor encephalitis is a severe autoimmune disease, first described in 2007.  Since then a number of cases have been published, suggesting that to date the disease is a considerably underdiagnosed entity. The clinical picture develops over a relatively long period of time and is initially characterised by psychiatric symptoms such as decreased levels of consciousness and hallucinations as well as paranoid behaviour. In the course of the disease neurological symptoms occur, in particular, seizures, autonomic dysfunction and dyskinesias. Due to the young age of many patients, the symptoms are often mistaken as to result from drug-induced psychosis. Anti-NMDA receptor Encephalitis was first described in young women with teratomas. In the past few years the disorder has also been reported in men and children and without any detectable neoplasia. The diagnosis is based on the characteristic clinical picture and supportive findings in MRI, EEG and the cerebrospinal fluid. Hereby, highly specific autoantibodies directed against the NR1 subunit of the NMDA-type glutamate receptors in the CSF (or serum) play an important role and should be sought specifically in any case of an "encephalitis of unknown cause". The prognosis of the disease is favourable, even when autonomic disorders entail ventilation and/or prolonged intensive care treatment is necessary. Nonetheless, the clinical outcome is highly dependent on an early diagnosis and immunotherapy without delay. In the case of a malignancy, tumour removal is also crucial. Taken together, an interdisciplinary approach including neurologists, psychiatrists, oncologists and gynaecologists is essential in order to detect and effectively treat this disorder.

Assessing self-awareness of dyskinesias in Parkinson's disease through movie materials.

The aim of our study was to determine self-awareness of dyskinesias and other core motor symptoms in Parkinson's disease (PD) through the use of movie presentations. A scale based on 10 movies (five depicting dyskinesias and five showing core symptoms) and the Self-Assessment Parkinson's Disease Disability Scale were administered to 21 patients (all with a Mini-Mental State Examination - MMSE score ≥ 25). Neurological assessment included the Unified Parkinson's Disease Rating Scale and the Hoehn-Yahr and Schwab-England scales. In addition, the MMSE, Beck Depression Inventory and Stroop task were administered. Overall, patient and caregiver ratings of dyskinesias and core PD symptoms were consistent. Two patients (9%) completely denied dyskinesias, while four patients (19%) significantly underestimated their dyskinesias. Our results confirm that poor self-awareness of symptoms in PD may be selective and that denial of dyskinesias affects only a minority of patients with normal cognitive status (MMSE ≥ 25). Most patients are aware of the presence of dyskinesias. Poor self-awareness of dyskinesias is associated with longer disease duration.

Longitudinal study of the socioeconomic burden of Parkinson's disease in Germany.

OBJECTIVE: To determine the health economic burden on patients with Parkinson's disease (PD) in Germany over a 12-month observation period and provide a comprehensive analysis of cost-driving factors. METHODS AND PATIENTS: Patients with PD (n = 145) were recruited from two clinical departments, two office-based neurologists and 12 GPs. Clinical evaluations were performed at baseline, 3, 6 and 12 months. Disease severity was measured using the Unified Parkinson's Disease Rating Scale (UPDRS). Cost data were assessed based on a patient diary and via personal structured interviews at the respective time-points. Costs were calculated from the societal perspective (2009 euro). Cost-driving factors were identified by multivariate regression analysis. RESULTS: Mean annual costs totalled euro20 095 per patient. Amongst direct costs, the highest expenditures (euro13 158) were for drugs (euro3526) and inpatient care including nursing homes (euro3789). Indirect costs accounted for 34.5% (euro6937) of total costs. Costs of home care provided by family accounted for 20% of direct costs. Cost-driving factors were identified for total costs (UPDRS, fluctuations, dyskinesia and younger age), direct costs (UPDRS, fluctuations), patient expenditures (UPDRS, depression) and drug costs (younger age). CONCLUSION: Parkinson's disease has a chronic course with growing disability and considerable socioeconomic burden. Disease progression leads to an increasing number of patients who require costly institutionalized care. Home care is a major factor influencing patients' families. Healthcare programmes aimed at reducing the burden of PD on society and individuals should consider cost-driving factors of PD.

Depressive symptoms in Parkinson disease correlate with impaired global and specific cognitive performance.

Consecutive patients in a Movement Disorders Center with Parkinson disease (PD) were offered to undergo complete neuropsychological testing and to complete the Beck Depression Inventory (BDI), regardless of their cognitive and behavioral status. A total of 82 patients were included in this cross-sectional study and had a mean age of 67.7 years, formal education of 14.8 years, PD duration of 101 months, Unified Parkinson Disease Rating Scale-Motor ''off'' score of 36.96, Mini-Mental State Examination (MMSE) score of 27.8 (range 19-30), and BDI score of 10.23 (SD 8.65). Beck Depression Inventory scores did not correlate with disease duration or motor scores but inversely correlated with the MMSE scores (r = -0.40; P < .001) and total Dementia Rating Scale (DRS) scores (r = -0.33; P < .01). Using a univariate regression analysis controlling for age, gender, education, and total Unified Parkinson Disease Rating Scales (UPDRS) score, the BDI scores had a significant and unique relationship with MMSE scores. However, when the BDI scores were correlated with specific cognitive domains, only the Boston Naming Test and the Hopkins Verbal Learning Test (HVLT) delayed recall remained significant after Bonferroni correction. Similarly, when comparing the cognitive performance of patients with PD who scored >14 on the BDI versus those who scored <14, only the mean score of the Boston Naming Test was different between the 2 groups. Our study shows that while depressive symptoms correlated with global cognitive performance, naming, verbal memory, and language are the most susceptible cognitive domains affected with depressive symptoms.

Quality of life in relation to mood, coping strategies, and dyskinesia in Parkinson's disease.

Given the variability of the results found in the literature, the current study is a step toward better clarifying the influence of motor and nonmotor factors on quality of life in Parkinson's disease. A total of 135 participants with Parkinson's disease were selected. Semistructured interviews were carried out, after which their mental and cognitive states were assessed using different scales (MINI, MADRS, EHD, HAMA). Finally, all participants completed 3 self-report questionnaires: 2 assessing coping strategies (WCC, CHIP) and 1, quality of life (Parkinson's disease questionnaire-39). It appears that the presence of dyskinesia, depression, and anxiety were linked to a poor quality of life. Interestingly, some different coping strategies, namely diversion as well as emotional strategies, were associated with a poor quality of life. These results encourage us to develop interventions focused on coping strategies and tailored to the emotional and clinical characteristics of each patient.

Oxcarbazepine use in paroxysmal kinesigenic dyskinesia: report on four patients.

The paroxysmal dyskinesias are a heterogeneous group of movement disorders. They are distinguished from one another by the mechanism through which abnormal movements are induced. Paroxysmal kinesigenic dyskinesia is the most common subtype, consisting of involuntary dyskinesias induced by purposeful movements. It typically responds favorably to anticonvulsants. This retrospective review describes four unrelated children and adolescents with idiopathic paroxysmal kinesigenic dyskinesia who were treated with oxcarbazepine. Each patient achieved complete resolution of signs with low-dose oxcarbazepine monotherapy.

Reading and spelling in children with severe speech and physical impairments: a comparative study.

BACKGROUND: Effective literacy skills are crucial in supporting communication for children with severe speech and physical impairments (SSPI). Reading and spelling difficulties are reported to be over-represented in this group, even where language and cognitive skills are age appropriate. AIMS: To compare the performance of children with SSPI on a range of language, reading and spelling tasks with that of their typically developing peers matched for receptive vocabulary and mental age. METHODS & PROCEDURES: A wide range of tasks was developed as part of a larger study exploring phonological awareness, reading and spelling skills. All tasks were accessible to children with severe physical impairments. Two groups of primary school-aged children were recruited, children with SSPI of average intelligence, and naturally speaking peers, matched for receptive vocabulary. Children were assessed individually on language, non-verbal cognition, phonological awareness, reading and spelling tasks. OUTCOMES & RESULTS: Sixteen children with SSPI were recruited. Their performance was compared with that of 15 naturally speaking peers, matched for receptive vocabulary scores. The children with SSPI achieved significantly lower scores on reading and spelling measures relative to their naturally speaking peers. However, at least one participant with SSPI scored at ceiling on each task, indicating that SSPI do not preclude the development of reading and spelling, at least in the early stages of literacy development. CONCLUSIONS & IMPLICATIONS: This study indicates that some children with severe speech impairments can develop phonological awareness, reading and spelling skills. However, the data suggest that phonological awareness may not be as good a predictor of reading and spelling abilities in this group of children as in typically developing children. Further research is needed to track development of reading and spelling, as well as the instructional support needed to scaffold more effective skills in these areas.

Nonverbal Hand Movement Durations Indicate Post-Concussion Symptoms of Athletes.

Methods of post-concussion diagnosis are still under debate with regard to sensitivity, objectivity, reliability, and costs. Spontaneous displays of nonverbal hand movement behavior during interaction are indicative of psychopathology and are relatively simple to record and analyze. Increased continuous (irregular) body-focused hand movement activity in particular indicates psychopathologies that overlap in symptomatology with those of sport-related concussions (SRCs). We therefore hypothesized that the duration of "irregular," "on body," and "act on each other" hand movements is increased in athletes with SRC who suffer from post-concussion symptoms. Three matched groups of 40 athletes were investigated: 14 symptomatic athletes with a concussion, 14 asymptomatic athletes with a concussion, and 12 non-concussed athletes. Using the Neuropsychological Gesture (NEUROGES)-Elan analysis system, four certified raters analyzed all nonverbal hand movements that were displayed during a videotaped standardized anamnesis about concussion history, incidence, course of action, and post-concussion symptoms. The duration of irregular Structure units among symptomatic athletes was significantly longer compared with asymptomatic athletes. Irregular, on body, and act on each other hand movement durations correlated with post-concussion symptoms. Whereas the duration of irregular units significantly predicted the post-concussion symptom score, working memory performances showed only marginal effects. Increased duration of irregular hand movement units indicates post-concussion symptoms in athletes with SRC. Because the recording of spontaneous displays of nonverbal hand movement behavior is relatively simple and cost efficient, we suggest using the neuropsychological analysis of hand movement behavior as a future diagnostic parameter of concussion management protocols.

Functional and structural correlates of abnormal involuntary movements in psychosis risk and first episode psychosis.

BACKGROUND: Abnormal involuntary movements (AIM) may occur throughout the course of psychosis. While AIM are thought to indicate striatal abnormalities, the functional and structural correlates of increased AIM remain elusive. Here, we examined the prevalence of AIM in patients with clinical high risk for psychosis (CHR), first episode psychosis (FEP) and clinical controls (CC). Furthermore, we tested the association of AIM with regional cerebral blood flow (rCBF), grey matter volume (GMV), and premorbid IQ. METHODS: We conducted a video-based analysis of AIM in patients with CHR (n = 45), FEP (n = 10) and CC (n = 39), recruited in the Early Detection and Intervention Center, Bern. Premorbid intelligence was evaluated using the Peabody Picture Vocabulary test. Additionally, arterial spin labeling MRIs and structural MRIs were acquired in a subgroup of the sample to investigate the association of AIM with rCBF and GMV. RESULTS: Higher total AIM scores were detected in CHR (p = 0.02) and FEP (p = 0.04) as compared to CC. When separated for different muscle groups, lips and perioral movements were significantly increased in CHR patients as compared to CC (p = 0.009). AIM scores correlated positively with rCBF in the premotor cortex, Brodmann area 6 (p < 0.05, FWE corrected). Negative correlations were found between AIM and GMV of the corresponding caudal middle frontal gyrus (p = 0.04, FWE corrected) and premorbid intelligence (p = 0.02). CONCLUSIONS: AIM were more frequent in the psychosis spectrum than in clinical controls. Neuroimaging findings indicate an involvement of cortical motor areas in abnormal motor behavior, instead of pure basal ganglia pathology.

Brief report: autistic symptoms, developmental regression, mental retardation, epilepsy, and dyskinesias in CNS folate deficiency.

We studied seven children with CNS folate deficiency (CFD). All cases exhibited psychomotor retardation, regression, cognitive delay, and dyskinesia; six had seizures; four demonstrated neurological abnormalities in the neonatal period. Two subjects had profound neurological abnormalities that precluded formal behavioral testing. Five subjects received ADOS and ADI-R testing and met diagnostic criteria for autism or autism spectrum disorders. They exhibited difficulties with transitions, insistence on sameness, unusual sensory interests, and repetitive behaviors. Those with the best language skills largely used repetitive phrases. No mutations were found in folate transporter or folate enzyme genes. These findings demonstrate that autistic features are salient in CFD and suggest that a subset of children with developmental regression, mental retardation, seizures, dyskinesia, and autism may have CNS folate abnormalities.

Involuntary masturbation and hemiballismus after bilateral anterior cerebral artery infarction.

Ischemia of the areas supplied by the anterior cerebral artery is relatively uncommon. In addition, combined hemiballismus and masturbation have rarely been reported in patients with cerebrovascular disease. We describe herein a 62-year-old right-handed man simultaneously exhibiting right side hemiballismus and involuntary masturbation with the left hand after bilateral infarction of the anterior cerebral artery territory. Right side hemiballismus was related to the disruption of afferent fibers from the left frontal lobe to the left subthalamic nucleus. Involuntary masturbation using the left hand was exclusively linked to a callosal type of alien hand syndrome secondary to infarction of the right side of the anterior corpus callosum. After 2 weeks, these abnormal behaviours were completely extinguished. This report stresses the wide diversity of clinical manifestations observed after infarction of the anterior cerebral artery territory.

[Movement disorders in stroke]. / Mouvements anormaux et accident vasculaire cérébral.

Dyskinesias are infrequent presentations in acute stroke (1%). They can be found more frequently as delayed presentations after a stroke, but the prevalence is not available from the literature. The full spectrum of hyper- and hypo-akinetic syndromes has been described, but three main pictures are rather specific of an acute stroke: limb shaking, hemichorea-hemiballism and unilateral asterixis. Besides limb shaking, that seems to reflect a transient diffuse ischemia of the frontosubcortical motor pathway, lesions are described at all levels of the frontosubcortical motor circuit including the sensorimotor frontoparietal cortex, the striatum, the pallidum, the thalamic nuclei, the subthalamic nucleus, the substantia nigra, the cerebellum, the brainstem and their interconnecting pathways, as ischemic or hemorrhagic strokes. The preferentially late development of dyskinesia could reflect the return to a more ancestral motor control level, the most functional possible with the remaining configuration of structures, elaborated by brain plasticity after stroke.

Movement abnormalities and the progression of prodromal symptomatology in adolescents at risk for psychotic disorders.

The link between movement abnormalities and psychotic disorders is presumed to reflect common neural mechanisms that influence both motor functions and vulnerability to psychosis. The prodromal period leading to psychotic disorders represents both a viable point for intervention and a developmental period that, if studied, could shed light on etiology; however, no published studies have examined the temporal progression of this link. A group with high levels of prodromal symptomatology (i.e., adolescents with schizotypal personality disorder [SPD]; n = 42) and both psychiatric controls (with other personality disorders or conduct disorder [OD]; n = 30) and nonpsychiatric controls ([NC]; n = 49) were recruited. Videotapes of structured psychiatric interviews were coded for movement abnormalities by raters blind to participants' diagnostic status, and follow-up assessments were conducted 1 year later. Controlling for psychotropic medications, the authors found that adolescents with SPD exhibited significantly more motor abnormalities in the face and upper body than did OD and NC controls. At baseline, movement abnormalities were positively correlated with the severity of positive, negative, and total prodromal symptoms. Within the SPD group, baseline movement abnormalities predicted symptom severity 1 year later. Movement abnormalities represent an early risk indicator that may be predictive of later symptom severity and potentially of psychosis onset.

Item response analysis of the Positive and Negative Syndrome Scale.

BACKGROUND: Statistical models based on item response theory were used to examine (a) the performance of individual Positive and Negative Syndrome Scale (PANSS) items and their options, (b) the effectiveness of various subscales to discriminate among individual differences in symptom severity, and (c) the appropriateness of cutoff scores recently recommended by Andreasen and her colleagues (2005) to establish symptom remission. METHODS: Option characteristic curves were estimated using a nonparametric item response model to examine the probability of endorsing each of 7 options within each of 30 PANSS items as a function of standardized, overall symptom severity. Our data were baseline PANSS scores from 9205 patients with schizophrenia or schizoaffective disorder who were enrolled between 1995 and 2003 in either a large, naturalistic, observational study or else in 1 of 12 randomized, double-blind, clinical trials comparing olanzapine to other antipsychotic drugs. RESULTS: Our analyses show that the majority of items forming the Positive and Negative subscales of the PANSS perform very well. We also identified key areas for improvement or revision in items and options within the General Psychopathology subscale. The Positive and Negative subscale scores are not only more discriminating of individual differences in symptom severity than the General Psychopathology subscale score, but are also more efficient on average than the 30-item total score. Of the 8 items recently recommended to establish symptom remission, 1 performed markedly different from the 7 others and should either be deleted or rescored requiring that patients achieve a lower score of 2 (rather than 3) to signal remission. CONCLUSION: This first item response analysis of the PANSS supports its sound psychometric properties; most PANSS items were either very good or good at assessing overall severity of illness. These analyses did identify some items which might be further improved for measuring individual severity differences or for defining remission thresholds. Findings also suggest that the Positive and Negative subscales are more sensitive to change than the PANSS total score and, thus, may constitute a "mini PANSS" that may be more reliable, require shorter administration and training time, and possibly reduce sample sizes needed for future research.

The anarchic hand syndrome and utilization behavior: a window onto agentive self-awareness.

Two main approaches can be discerned in the literature on agentive self-awareness: a top-down approach, according to which agentive self-awareness is fundamentally holistic in nature and involves the operations of a central-systems narrator, and a bottom-up approach that sees agentive self-awareness as produced by lowlevel processes grounded in the very machinery responsible for motor production and control. Neither approach is entirely satisfactory if taken in isolation; however, the question of whether their combination would yield a full account of agentive self-awareness remains very much open. In this paper, I contrast two disorders affecting the control of voluntary action: the anarchic hand syndrome and utilization behavior. Although in both conditions patients fail to inhibit actions that are elicited by objects in the environment but inappropriate with respect to the wider context, these actions are experienced in radically different ways by the two groups of patients. I discuss how top-down and bottom-up processes involved in the generation of agentive self-awareness would have to be related in order to account for these differences.