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Antidyskinetic drug therapy for pediatric movement disorders.

The pharmacologic armamentarium used to treat dyskinesias in childhood is increasing. Anticonvulsant drugs as a class are still some of the broadest-spectrum antidyskinetic agents, probably because the class includes so many differently acting drugs or because dyskinesias are manifestations of subcortical electrical events. This group is enhanced by recent developments in gamma-aminobutyric acid and glutamate receptor pharmacology, which promise new antidyskinetic drugs. Other drugs acting at receptors for monoamines (dopamine, norepinephrine, and serotonin), acetylcholine, opioids, or histamine may provide symptomatic improvement. Fewer pharmacotherapies address the underlying pathophysiology of movement disorders. Of these, drugs or biologicals for immunomodulation are the most developed, but the group also includes antioxidants, cofactors, metabolic inhibitors, and chelators. There is potential for drugs that block the neurotoxic effects of glutamate to treat movement disorders and reverse or prevent brain injury. Peripheral blockade of focal dyskinesias through botulinum toxin offers a useful alternative to drugs in some patients.

Child↗

Differential rates of psychopathology symptoms in periodic limb movement disorder, obstructive sleep apnea, psychophysiological insomnia, and insomnia with psychiatric disorder.

STUDY OBJECTIVE: To determine patterns and relative intensity of psychopathology, as measured by the Minnesota Multiphasic Personality Inventory (MMPI), in 108 patients with either psychophysiological insomnia (PI; n=20), insomnia with psychiatric disorder (IPD; n=30), periodic limb movement disorder (PLM; n=28), or obstructive sleep apnea (OSA; n=30). DESIGN: Cross-sectional. SETTING: University sleep disorders center. MEASUREMENTS AND RESULTS: Subjects completed the MMPI prior to overnight diagnostic polysomnographic assessment followed by Multiple Sleep Latency Test (MSLT). Seventy five percent of the entire sample had at least one MMPI elevation (T>70). Groups showed significant baseline differences in age, BMI, and MSLT latency (all ps<.05). Logistic regression indicated that even after statistically controlling for these three diagnostic covariates, MMPI elevation was more likely among PLM and IPD patients than OSA or PI patients (all ps<.05). Followup pairwise comparisons indicated that this same pattern of group differences occurred for the Depression, Psychasthenia, and Schizophrenia scales (all ps<.05). CONCLUSIONS: Irrespective of age, obesity, and daytime sleepiness, patients with untreated PLM or IPD are more likely to experience clinically significant psychological difficulties than those with either OSA or PI. These differences are most likely to be manifested in terms of depressive symptoms, anxiety symptoms (tension, worry, guilt), social alienation, and diminished mental concentration. Finally, PLM may be associated with greater MMPI elevations than previously suspected, and agree with earlier clinical reports of high rates of psychiatric treatment in PLM.

Adult↗

[New treatments in movement disorders].

In recent years there have been considerable advances in the field of movement disorders which have decisively transformed not only the comprehension of the genetics and the pathophysiology of different diseases but have also improved the quality of life of these patients. Examples of these already available advances include the introduction of new treatments for previously untreatable diseases, such as botulinum toxin for dystonia, new therapeutic options or new forms of administration of levodopa for Parkinson disease, such as delayed levodopa, catecol-O-methyl transferase inhibitors and monotherapy with the classical and new dopaminergic agonists or new surgical techniques for previously unapproachable complications, such as dyskinesias in advanced Parkinson's disease. This study reviews the current treatment of Parkinson's disease, essential tremor, dystonia and different forms of choreas and indicates some of the experimental therapies which open renewed perspectives for neurodegenerative diseases, mainly Huntington's chorea and Parkinson's disease, such as the drugs with possible neuroprotective action, glutamatergic transmission reducers, neurotrophic factors and neuronal implants.

Humans↗

The Schedule for the Assessment of Drug-Induced Movement Disorders (SADIMoD): test-retest reliability and concurrent validity.

The SADIMoD is a newly developed instrument, consisting of a compilation of rating scales, to measure the severity of drug-induced movement disorders: dystonia, dyskinesia, Parkinsonism, akathisia, ataxia, and several types of tremors. The test-retest reliability of this scale and the concurrent validity with the Abnormal Involuntary Movement Scale (AIMS), the Simpson-Angus Scale (SEE) and the Barnes Akathisia Scale (BAS) was assessed in 31 patients [20 male/11 female; 57.1+/-16.5 yr (mean+/-S.D.)] with a variety of movement disorders by six teams of investigators. The teams were trained by means of a standard package of instruction material to such an extent that a single member of the team could represent the entire team. Each patient was rated according to the AIMS, SEE and BAS and recorded on videotape according to the SADIMoD Schedule. These video-recordings were scored twice; first, in consensus by the entire team and secondly [110.3+/-58.0 d (mean+/-S.D.) later] by a single representative of that team. One team underwent a major change between scoring and was excluded from this analysis. Despite these difficult circumstances, these first and second ratings correlated to a highly significant degree with Spearman's correlation coefficients of 0.57 to 0.88 (median 0.69). The homogeneity of the applied scales was good (Cronbach's a = 0.75-0.94). Convergent validity was found between the SADIMoD dyskinesia and (to a lesser extent) dystonia scales and the AIMS as well as between the akathisia sub-scales and the BAS, with divergent validity with the other sub-scales. The SEE discriminated less well between the Parkinsonism sub-scale and the other sub-scales.

Journal Article↗

Complex movement disorders induced by fluoxetine.

We report two cases of complex movement disorders induced by fluoxetine. A 72-year-old woman developed rhythmic palatal movements, myoclonus, chorea, and possibly dystonia after 2 years of therapy with fluoxetine. On withdrawal of fluoxetine, the movements abated after 5 days and did not recur. The second patient, a 58-year-old man, developed myoclonic jerking and rapid, stereotypic movements of his toes after a year of fluoxetine therapy. These complex movements have not been reported previously as an adverse effect of fluoxetine.

Aged↗

Periodic limb movement disorder of sleep in children.

To characterize periodic limb movement disorder (PLMD) in a cohort of prepubertal children we examined sleep-related identifiable differences between children with PLMD and attention-deficit/hyperactivity disorder (ADHD), PLMD alone, and age-matched controls. Children were selected from a chart review of all children referred to a pediatric sleep medicine center and from a community survey of 5-7-year-old-children. Polysomnography (PSG) and parental report data from all children identified as having periodic limb movement index (PLMI) >5 were reviewed and compared with a cohort of age-matched controls. A total of 8.4% of children in the clinic-referred sample, and 11.9% of the children recruited from the community had PLMI >5. Of those, 44.4% were identified as having ADHD. Children with PLMD had significantly lower percentage of rapid eye movement (REM) than control children (P < 0.001). Children in the PLMD/ADHD group had a significantly greater number of arousals associated with PLM (PLMa) than children with PLMD only (P < 0.05). While a relationship between ADHD and PLMD was observed, it was weaker than previous reports (Chervin, R. D. et al. Sleep, 2002; 25: 213; Chervin, R. D. and Archbold, K. H. Sleep, 2001; 24: 313; Picchietti et al. J. Child Neurol., 1999; 13: 588; Picchietti et al. Mov. Disord., 1999; 14: 1000; Picchietti and Walters Sleep, 1999; 22: 297). Children in the PLMD/ADHD group were more likely to have PLMas than were children with PLMD only. We postulate that rather than a direct relationship between ADHD and PLMD, this link may be mediated by the presence of reduced REM sleep and more importantly by the sleep fragmentation associated with PLM-induced arousals.

Attention Deficit Disorder with Hyperactivity↗

Etiology of parkinsonism in a Brazilian movement disorders clinic.

OBJECTIVE: The aim of the present study is to investigate whether there are geographic differences in the etiology of parkinsonism (PA). BACKGROUND: 72% of patients with PA evaluated at movement disorders clinics in the Northern Hemisphere are diagnosed with Parkinson's disease (PD). Data regarding other regions are not available. METHODS: We reviewed the charts of all patients with PA seen at the Federal University of Minas Gerais Movement Disorders Clinic from July 1993 through October 1995. PA was diagnosed by the presence of at least two of the following: rest tremor, bradykinesia, rigidity, and postural instability. The different etiologies were diagnosed based on standard clinical criteria. RESULTS: During the period of the study, PA was recognized in 338 subjects. The following clinical diagnoses were made: PD (68.9%), drug-induced PA (DIP) (13.3%), vascular PA (4.7%), Progressive supranuclear palsy (PSP) (2%), multiple system atrophy (MSA) (1.8%), others (9.7%). Cinnarizine, haloperidol and flunarizine were the commonest drugs related to DIP. CONCLUSIONS: Similarly to other studies, PD accounts for about 70% of PA patients. However, there are differences between our results and previous series. DIP is much more common in the present series. This may be accounted for a more liberal use of antidopaminergic drugs in our environment, especially Calcium channel blockers. The lower frequency of MSA and PSP in our study may reflect a short follow-up, since many patients initially diagnosed with PD later are found to have Parkinson-plus syndromes.

Aged↗

Effects of repeated drug holidays on serum haloperidol concentrations, psychiatric symptoms, and movement disorders in schizophrenic patients.

In a crossover experiment the authors investigated the effects of repeated weekly, 2-day, haloperidol drug holidays on serum haloperidol concentrations, mental status, and neuroleptic-induced movement disorders in seven chronic schizophrenic patients. Haloperidol concentrations decreased about 64% during the initial 36 hours of drug holiday and subsequently increased slightly during the next 24 hours of drug holiday. Two-day weekly drug holidays for 6 weeks resulted in an average reduction of 25% in serum haloperidol concentrations at all drug holiday points. Mental status and movement disorders scores, rated by observers blind to the drug-holiday condition, were not significantly affected by drug holidays.

Drug Administration Schedule↗

Local cerebral glucose utilization in the AS/AGU rat: a mutant with movement disorders.

The AS/AGU mutant rat is characterized by a wide staggering gait and a movement disorder of the hindlimbs. Local cerebral glucose utilization in the brain was investigated using the [14C]2-deoxyglucose autoradiographic technique to map any functional alterations in the mutant AS/AGU (agu/agu) compared with Albino Swiss controls (+/+). Locomotor tests were also performed to confirm the phenotypic assignment of the animals. Statistically significant reductions in glucose utilization were apparent in 12 of the 44 regions examined in the AS/AGU animals. The regions showing the most significant differences (P < 0.01) from the control AS strain were the substantia nigra pars compacta (-23%) and medial geniculate body (-17%). Statistically significant decreases (P < 0.05 and P < 0.02) in glucose utilization ranging from -15 to -26% were also displayed in the superior colliculus superficial layer, auditory cortex, ventroposterior nucleus of the thalamus, molecular layer of the hippocampus, dentate gyrus, medial amygdaloid nucleus, median raphe nucleus, subthalamic nucleus, medial preoptic area of the hypothalamus and anterior hypothalamus. In no region studied was the mean value of glucose use in the AS/AGU rat greater than in the control animals. The results of this study complement previous behavioural and neurochemical characterization studies of this mutant, confirm that the disorder involves functional disturbances of the basal ganglia, and demonstrate the involvement of the limbic system and some sensory systems.

Animals↗

Movement disorders in sleep: Parkinson's disease and restless legs syndrome.

In recent years, sleep abnormalities have increasingly been observed in patients with movement disorders. During sleep, most patients with Parkinson's disease also exhibit the movements characteristically seen during the wake period. Movement activity during sleep may impair sleep quality and lead to daytime sleepiness and reduced quality of life. Disordered REM sleep with enhanced muscle tone is common in patients with neurodegenerative disease, and may precede the clinically evident symptoms of Parkinson's disease by years. Sleep disorders in patients with Parkinson's disease are common, and require the application of individual treatment strategies. A further frequent disorder primarily classified as a sleep disorder (dyssomnia) is the restless legs syndrome (RLS), which is closely related to the nocturnal periodic limb movement disorder and affects up to 15% of the population. The present review focuses on nocturnal motor activity and sleep in Parkinson's disease and RLS.

Cerebral Cortex↗

Postural asymmetry and movement disorder after unilateral microinjection of adrenocorticotropin 1-24 in rat brainstem.

A unilateral microinjection of adrenocorticotropin 1-24 in the rat brainstem in the region of the locus ceruleus resulted in postural asymmetry and movement disorder that resembled human dystonia, the severity and duration (2 to 3 days) being dose-dependent. These results show for the first time that neuropeptides in the brainstem may modulate posture and movement, and they suggest that some forms of movement disorder such as dystonia may be due to a disordered regulation of postural and locomotor mechanisms by adrenocorticotropin 1-24.

Adrenocorticotropic Hormone↗

Iron deficiency in two adolescents with conduct, dysthymic and movement disorders.

Enquiry into a marginally subnormal hemogram in two adolescents with complex conduct, dysthymic and movement disorders uncovered a striking iron deficiency and prompted a trial of replacing psychotropic medication with iron therapy. The rationale of iron therapy for behavioural disturbance was examined from the clinical, neurochemical and psychopharmacological points of view. Although further study is required to confirm the therapeutic efficacy and to define the precise nature of iron deficiency in conduct disorder, the weight of the evidence suggests that correcting the nutrient deficit may be an essential step toward a refinement of therapeutic strategies. The presence of a borderline hemogram, hypermenorrhea and malnutrition should alert clinicians to the possibility of iron deficiency, and laboratory screening for hypoferremia should be considered when assessing conduct disorder.

Acting Out↗

[Functional imaging in movement disorders].

Parkinsonian syndromes in the early stage are often misdiagnosed in the general practice. Neuroimaging brings information about changes in the anatomical structure of the brain, which are not typical of movement disorders. The introduction of a functional imaging with the use of presynaptic tracers of the dopaminergic system enables proving nigrostriatal degeneration and supporting the clinical diagnosis of Parkinsonism even in the early phase of the disease. Availability of the single photon emission computer tomography (SPECT) imaging in the nuclear medicine departments gives an opportunity to introduce this neuroimaging method in Poland. In this review we present methods of functional imaging of the brain, particularly of the dopaminergic pathway with the use of SPECT tracers. The role of functional imaging in movement disorders workup for the neurologist is discussed.

Brain↗

Progressive multifocal leukoencephalopathy presenting with an isolated focal movement disorder.

Progressive multifocal leukoencephalopathy (PML) is a rare but fatal papovavirus infection of the central nervous system predominantly affecting immunocompromised patients. Although the basal ganglia circuitry may be involved in the pathology of PML, movement disorders are exceedingly rare as presenting symptoms and have not been described as isolated features in such patients. We report a previously healthy, immunocompetent 24-year-old woman with histologically proven PML who presented with a focal movement disorder of the left arm as an isolated symptom for many months before diagnosis.

Adult↗

Deep brain stimulation for movement disorders.

Chronic deep brain stimulation (DBS) is a promising technique for the treatment of movement disorders. Thalamic stimulation is now an established surgical procedure for parkinsonian and essential tremor. Pallidal and subthalamic stimulation are under active investigation as treatments for Parkinson's disease. Although high-frequency DBS at these sites has similar behavioral effects as lesioning, the physiologic mechanisms underlying the beneficial effect of DBS is not well understood and may be extremely complex. DBS offers a potential advantage over ablative therapy because stimulation-induced complications are reversible, and the stimulation parameters are adjustable to minimize complications and maximize therapeutic effects. With this added safety, bilateral stimulation or use of a stimulator following a prior procedure may be preferable to bilateral ablative procedures.

Electric Stimulation Therapy↗

Botulinum toxin treatment in patients with focal dystonia and hemifacial spasm. A multicenter study of the Italian Movement Disorder Group.

In six Centers belonging to the Italian Movement Disorder Study Group, the efficacy of botulinum toxin treatment was evaluated in an open collaborative study in 251 patients with focal dystonia and hemifacial spasm. The percentage of functional improvement ranged from 66% to 81% in patients with blepharospasm, from 40% to 51% in patients with spasmodic torticollis and from 73% to 81% in those with hemifacial spasm. Good results were also obtained in patients with oromandibular dystonia, laryngeal dystonia and writer's cramp. Side effects were mild and transient. Local botulinum toxin injection is the first choice symptomatic treatment in focal dystonia and hemifacial spasm.

Adult↗

Rhythmic movement disorder in children.

How should sleep-related rhythmic movements in children be assessed and treated? Rhythmic movement disorder (RMD) represents an unusual variety of childhood parasomnia characterized by repetitive motion of the head, trunk, or extremities, which usually occurs during the transition from wakefulness to sleep or arises during sustained sleep. Although the condition most often affects infants and toddlers in a transient and self-limited fashion, the condition occasionally persists in a problematic fashion, which may nevertheless be amenable to treatment. Since RMD may occasionally cause injury or resemble nocturnal seizure, prompt recognition, and appropriate management on the part of the clinician is essential. This article will examine the spectrum of RMD in children, including their common clinical manifestations; data regarding their epidemiology and natural history; the role of polysomnography, electroencephalography; and other diagnostic testing. Potential causes of the condition and available methods of treatment are also examined.

Child↗

Sleep bruxism; an overview of an oromandibular sleep movement disorder. REVIEW ARTICLE.

Sleep bruxism (SB) is a stereotyped movement disorder characterized by grinding or clenching of the teeth during sleep. The majority of the population will at some time during their lifetime grind or clench their teeth. It becomes a pathological condition when the subject presents severe tooth damage or complains of non-restorative sleep. The prevalence of SB is difficult to estimate, since quite often the subjects are unaware of having the disorder. There is no gender difference. SB is more frequent in the younger generation, with a decline over age. The symptom recognized in children can persist in adulthood. The aetio-pathophysiology is still unclear. SB has been associated with tooth interference, psychosocial and environmental factors, brain transmitters and basal ganglia dysfunction. Attempts have been made to specify the personality traits of bruxers, reported to be greater anxiety or vulnerability to stress; however, this is still controversial. SB subjects were observed to present vigilance-sleepiness and somatic problems. However, they are generally good sleepers. Some authors reported SB during all sleep stages, others observed the majority of bruxe episodes during light sleep and REM and often associated with arousal transients. No abnormalities of the autonomic nervous system could be shown in awake SB subjects. While some studies have shown an association between SB and PLM or breathing disorders, others did not confirm this. There is no specific treatment for SB: each subject has to be individually evaluated and treated. Three management alternatives are used: dental, pharmacological and psychobehavioural.

Journal Article↗