Choreiform Dyskinesia Research Articles

Clinico-Genetic Profiles of Seven Patients With PINK1-Related Parkinson's Disease: A Case Series From a Tertiary Care Centre in India and a Review of the Literature.

Recessive variants in the PINK1 gene are known causes of early-onset Parkinson's disease (EOPD). To describe the clinical features and genetic profiles of patients with PINK1-related Parkinson's disease (PARK-PINK1) mutations. We conducted a retrospective chart review of the demographic, clinical and genetic details of patients from our database carrying biallelic PINK1 variants. A total of 7 patients whose median age at onset was 33 years (range: 20-49) were recruited. All had asymmetrical onset, tremors were present in 4 patients, abnormal posturing was present in 2 patients, and slowness was present in 1 patient. The parkinsonism phenotype was noted in 6 patients (with dystonia in four) and isolated dystonia in one. Among the 6 patients with parkinsonism, five had rest tremors, all had good levodopa responses, and four had motor fluctuations with choreiform dyskinesia. Exome sequencing revealed biallelic pathogenic/likely pathogenic variants, five of which were novel. PARK-PINK1 presents as an EOPD with tremor-predominant phenotype, good levodopa-responsiveness, early motor fluctuation and dyskinesia. We describe five novel variants in PINK1 gene.

Practically Defined Off-State Dyskinesia Following Repeated Intraputamenal Glial Cell Line-Derived Neurotrophic Factor Administration.

We recently showed that by employing an enhanced drug-delivery approach, repeated administration of glial cell line-derived neurotrophic factor (GDNF) can produce a spatially distributed increased 18 F-DOPA positron emission tomography (PET) uptake, suggesting sprouting of dopaminergic terminals throughout the putamen structure. Despite this, we failed to prove a significant measurable clinical response. Since, however, we have identified a subject demonstrating a temporal relationship between repeated GDNF infusions and dyskinesia arising in the practically defined off (pracoff) state. To describe the development of pracoff dyskinesia across our study population and consider its utility as an indicator that trophic factor-induced terminal sprouting can affect enhanced endogenous dopamine levels. This was a blinded retrospective analysis of videotaped motor assessments at eight weekly study visits. Dyskinesia in the pracoff and supramaximal on state were rated using the Clinical Dyskinesia Rating Scale. Logistic regression was employed to explore the predictors of pracoff dyskinesia. Generalized estimated equations were used to estimate the cumulative effect of repeated GDNF infusions. Mild-moderate choreiform dyskinesia in the pracoff state were seen in 47 assessments in 17 (n=41) subjects. During the 18-month timeframe, each subsequent 8-week period of receiving GDNF increased the risk of demonstrating pracoff state dyskinesia by 34% (odds ratio [OR], 1.34 (95% confidence interval [CI], 1.20, 1.50); P< 0.001). An increasing supramaximal on dyskinesia score (OR, 1.17 [95% CI, 1.07, 1.30]; P= 0.001) also increased the likelihood of pracoff dyskinesia at that visit. We report the first description of increasingly prevalent pracoff-state dyskinesia developing during the course of a trophic factor study. This may provide a surrogate marker that GDNF can enable recovery of endogenous dopamine release even in advanced Parkinson's disease. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Choreiform Dyskinesia as a Sole Manifestation of Alcohol Withdrawal Syndrome

Choreiform Dyskinesia as a Sole Manifestation of Alcohol Withdrawal Syndrome

Minor Neurological Dysfunctions (MNDs) in Autistic Children without Intellectual Disability.

Background: Children with autism spectrum disorder (ASD) require neurological evaluation to detect sensory-motor impairment. This will improve understanding of brain function in children with ASD, in terms of minor neurological dysfunctions (MNDs). Methods: We compared 32 ASD children without intellectual disability (IQ ≥ 70) with 32 healthy controls. A standardized and age-specific neurological examination according to Touwen was used to detect the presence of MNDs. Particular attention was paid to severity and type of MNDs. Results: Children with ASD had significantly higher rates of MNDs compared to controls (96.9% versus 15.6%): 81.3% had simple MNDs (p < 0.0001) and 15.6% had complex MNDs (p = 0.053). The prevalence of MNDs in the ASD group was significantly higher (p < 0.0001) than controls. With respect to specific types of MNDs, children with ASD showed a wide range of fine manipulative disability, sensory deficits and choreiform dyskinesia. We also found an excess of associated movements and anomalies in coordination and balance. Conclusions: Results replicate previous findings which found delays in sensory-motor behavior in ASD pointing towards a role for prenatal, natal and neonatal risk factors in the neurodevelopmental theory of autism.

Paroxetine induced reversible dyskinesia: a case report

Selective serotonin reuptake inhibitors (SSRI) are the primary medications that have been used recently for the treatment of psychiatric disorders. Paroxetine is one of the medications in the category of SSRI. In the literature, dyskinesia cases related to paroxetine are quite rare in comparison to other movement disorders, and the ones that have been presented are facial dyskinesia. The purpose of this report is to present an involuntary choreiform dyskinesia case that appears in the extremities related to addition of paroxetine on chlorpromazine. To our knowledge, our case, extremity dyskinesia related to paroxetine is the first case that has been observed so far.

TC-8831, a nicotinic acetylcholine receptor agonist, reduces l-DOPA-induced dyskinesia in the MPTP macaque

Long-term l-DOPA treatment for Parkinson's disease (PD) is limited by motor complications, particularly l-DOPA-induced dyskinesia (LID). A therapy with the ability to ameliorate LID without reducing anti-parkinsonian benefit would be of great value. We assessed the ability of TC-8831, an agonist at nicotinic acetylcholine receptors (nAChR) containing α6β2/α4β2 subunit combinations, to provide such benefits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- (MPTP) lesioned macaques with established LID.Animals were treated orally for consecutive 14-day periods with twice-daily vehicle (weeks 1–2) or TC-8831 (0.03, 0.1 or 0.3 mg/kg, weeks 3–8). l-DOPA was also administered, once-daily, (weeks 1–12, median-dose 30 mg/kg, p.o.). For the following two-weeks (weeks 9–10), TC-8831 was washed out, while once-daily l-DOPA treatment was maintained. The effects of once-daily amantadine (3 mg/kg, p.o.) were then assessed over weeks 11–12. LID, parkinsonism, duration and quality of ON-time were assessed weekly by a neurologist blinded to treatment.TC-8831 reduced the duration of ‘bad’ ON-time (ON-time with disabling dyskinesia) by up to 62% and decreased LID severity (median score 18 cf. 34 (vehicle), 0.1 mg/kg, 1–3 h period). TC-8831 also significantly reduced choreiform and dystonic dyskinesia (median scores 6 and 31 cf. 19 and 31 respectively (vehicle), both 0.03 mg/kg, 1–3 h). At no time did TC-8831 treatment result in a reduction in anti-parkinsonian benefit of l-DOPA. By comparison, amantadine also significantly reduced dyskinesia and decreased ‘bad’ ON-time (up to 61%) but at the expense of total ON-time (reduced by up to 23%).TC-8831 displayed robust anti-dyskinetic actions and improved the quality of ON-time evoked by l-DOPA without any reduction in anti-parkinsonian benefit.

Minor neurological dysfunction and cognition in 9-year-olds born at term

BackgroundIn children with developmental disorders, motor problems often co-occur with cognitive difficulties. Associations between specific cognitive deficits underlying learning problems and minor neurological dysfunction (MND) are still unknown. AimsTo assess associations between specific types of MND as clinical markers of non-optimal brain function and performance in specific cognitive domains. Study designPart of a randomized controlled trial. SubjectsThree hundred and forty one 9-year-old children born at term (177 boys, 164 girls). Outcome measuresChildren were neurologically assessed to detect eight types of MND: mild dysfunction in posture and muscle tone, reflexes, coordination, fine manipulative ability, sensory function, cranial nerve function, choreiform dyskinesia and excessive associated movements. Cognitive function in the domains of attention, memory and language was evaluated using the Test of Everyday Attention for Children (TEA-Ch), a developmental neuropsychological assessment (NEPSY) and the Children's Memory Scale. ResultsFine manipulative disability and coordination problems were associated with lower scores on attention, memory and learning and language, other types of MND were not. Girls with coordination problems performed significantly worse on attention/executive function than those without this dysfunction; however, in boys, such association was absent. ConclusionParticularly, fine manipulative disability and coordination problems were associated with worse cognitive function in the domains of attention, learning and memory and language. Previous and present data suggest a minor sex difference in neurocognitive associations: in girls dysfunction of the cerebello-thalamo-cortical pathways may be associated with cognitive deficits, while in boys cognitive impairment may be associated with dysfunction of cortico-striato-thalamo-cortical pathways.

Topography of dyskinesias and torticollis evoked by inhibition of substantia nigra pars reticulata

GABAergic neurons of the substantia nigra pars reticulata (SNpr) and globus pallidus pars interna (GPi) constitute the output pathways of the basal ganglia. In monkeys, choreiform limb dyskinesias have been described after inhibition of the GPi, but not the SNpr. Given the anatomical and functional similarities between these structures, we hypothesized that choreiform dyskinesias could be evoked by inhibition of an appropriate region within the SNpr. The GABAA receptor agonist, muscimol, was infused into various sites within the SNpr and the adjacent STN of freely moving macaques. The effect of the GABAA antagonist, bicuculline (BIC), was also examined. Muscimol (MUS) in SNpr evoked the following: (1) choreiform dyskinesias of the contralateral arm and/or leg from central and lateral sites; (2) contralaterally directed torticollis from central and posterior sites; and (3) contraversive quadrupedal rotation from anterior and lateral sites. MUS infusions into the adjacent SN pars compacta or STN were without effect, ruling out a contribution of drug spread to adjacent structures. BIC in SNpr induced ipsiversive postures without choreiform dyskinesia or torticollis, whereas in the STN, it evoked ballistic movements. This is the first report of choreiform dyskinesia evoked by inhibition of the SNpr. This highly site-specific effect was obtained from a restricted region within the SNpr distinct from that responsible for inducing torticollis. These results suggest that overactivity of different SNpr outputs mediates choreiform dyskinesia and torticollis. These abnormalities are symptoms of dystonia, Huntington's disease, and iatrogenic dyskinesias, suggesting that these conditions may result, in part, from a loss of function in SNpr efferent projections.

Prenatal Exposure to Organohalogens, Including Brominated Flame Retardants, Influences Motor, Cognitive, and Behavioral Performance at School Age

BackgroundOrganohalogen compounds (OHCs) are known to have neurotoxic effects on the developing brain.ObjectiveWe investigated the influence of prenatal exposure to OHCs, including brominated flame retardants, on motor, cognitive, and behavioral outcome in healthy children of school age.MethodsThis study was part of the prospective Groningen infant COMPARE (Comparison of Exposure-Effect Pathways to Improve the Assessment of Human Health Risks of Complex Environmental Mixtures of Organohalogens) study. It included 62 children in whose mothers the following compounds had been determined in the 35th week of pregnancy: 2,2′-bis-(4 chlorophenyl)-1,1′-dichloroethene, pentachlorophenol (PCP), polychlorinated biphenyl congener 153 (PCB-153), 4-hydroxy-2,3,3′,4′,5-pentachlorobiphenyl (4OH-CB-107), 4OH-CB-146, 4OH-CB-187, 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47), BDE-99, BDE-100, BDE-153, BDE-154, and hexabromocyclododecane. Thyroid hormones were determined in umbilical cord blood. When the children were 5–6 years of age, we assessed their neuropsychological functioning: motor performance (coordination, fine motor skills), cognition (intelligence, visual perception, visuomotor integration, inhibitory control, verbal memory, and attention), and behavior.ResultsBrominated flame retardants correlated with worse fine manipulative abilities, worse attention, better coordination, better visual perception, and better behavior. Chlorinated OHCs correlated with less choreiform dyskinesia. Hydroxylated polychlorinated biphenyls correlated with worse fine manipulative abilities, better attention, and better visual perception. The wood protective agent (PCP) correlated with worse coordination, less sensory integrity, worse attention, and worse visuomotor integration.ConclusionsOur results demonstrate for the first time that transplacental transfer of polybrominated flame retardants is associated with the development of children at school age. Because of the widespread use of these compounds, especially in the United States, where concentrations in the environment are four times higher than in Europe, these results cause serious concern.

Developmental coordination disorder: is clumsy motor behavior caused by a lesion of the brain at early age?

Children presenting with Developmental Coordination Disorder or clumsiness often exhibit signs of minor neurological dysfunction (MND). The data of the Groningen Perinatal Project, a long-term follow-up project .on the relations between prenatal and perinatal adversities and neurological, behavioral, and cognitive development revealed that two basic forms of MND can be distinguished: simple and complex MND. During school age children with simple MND are characterized by the presence of one or two dysfunctional clusters of MND, in adolescence by the presence of choreiform dyskinesia or hypotonia. Probably the major sources of origin of simple MND are genetic constitution and stress during early life. Simple MND might reflect the lower tail of the normal distribution of the quality of non-pathological brain function. In line with this hypothesis is the finding that simple MND is associated with only a moderately increased risk for learning and behavioral problems. Children with complex MND present at school age with at least three dysfunctional clusters of MND, in adolescence with problems in fine manipulation or coordination. Perinatal adversities play an evident etiological role in the development of complex MND, suggesting that it might be attributed to a lesion of the brain at early age. In line with this idea is the finding that complex MND shows .a strong correlation with attention and learning problems.

Neuroinhibición talámica para el tratamiento del temblor postraumático

Severe head trauma could be followed by a wide range of movement disorders. Usually, they appear as a moderate or severe intention tremor that causes great patient disability. Those movement disorders use to be refractary to medical treatment, although sometimes they would be spontaneusly controlled by a year.14 year old boy who suffered severe head trauma at age of 8. One year after the injury he developed an action tremor and choreiform dyskinesia with hemibalistic features evocated by the movement. Medical treatment was ineffective. Due to the great patients disability, we chose the surgical treatment based on the placement of an stimulation electrode in thalamic Vop/Vim complex, obtaining a tremor abolition with an improvement in the scales of tremor and quality of life.Surgical treatment of postraumatic tremors tryes to improve in terms of function and activities of daily living, more than suppresion of a symptom. The aim of this treatment is cut the palidal thalamic cortical pathways. Anyway, target is defined by the tremor related cells and, it is more a functional target than an anatomical one. We prefer stimulation more than lesion, due to the lack of brain definitive injury because its reversibility and adjustability features.

Late neurological sequelae of non‐hemolytic hyperbilirubinemia of healthy term neonates

Grimmer I, Berger‐Jones K, Bührer C, Brandl U, Obladen M. Late neurological sequelae of non hemolytic hyperbilirubinemia of healthy term neonates. Acta Pædiatr 1999; 88: 661‐3. Stockholm. ISSN 0803‐5253Records of the only children's hospital equipped to perform exchange transfusions in West Berlin were used to identify all 29 non‐hemolytic healthy term newborns with total serum bilirubin between 20 and 30 mg/dL, 16 of whom were available for follow‐up neurological examination according to Touwen. Compared to 18 case controls with bilirubin &lt;12 mg/dL, jaundiced children scored significantly worse only on the choreiform dyskinesia scale. □Bilirubin, infant, neurological impairment, newborn

Neurobehavioural relationships after the onset of puberty.

The behavioural and cognitive development were studied of 68 children with and 259 without minor neurological function (MND) at 14 years, when the majority of children showed three or more physical signs of puberty. MND was differentiated into fine manipulative disability, co-ordination problems, choreiform dyskinesia and hypotonia. The normal group was subdivided into those who had been normal at 12 years and those who had had MND. All types of MND were related to cognitive and behavioural problems. Fine manipulative disability was related to behavioural and cognitive difficulties; co-ordination problems to learning difficulties; and choreiform dyskinesia and hypotonia were related to attention difficulties and school failure, notwithstanding normal IQ. Besides MND, socio-economic class, family adversities and female gender contributed to the development of behavioural and cognitive problems. The behaviour of children with MND at 12 years who were normal at 14 years did not differ from that of normal children.

A follow-up study of child psychiatric clinic attenders with minor neurological dysfunction.

Thirty-two child psychiatric patients with minor neurological dysfunction (MND) were followed-up after a mean interval of 5.3 years. Six clusters were analyzed that measured posture and muscle tonus, reflexes, coordination and balance, fine manipulative ability, choreiform dyskinesia, and associated movements. In the majority of cases, remission occurred for posture and muscle tonus, and choreiform dyskinesia and reflexes. Problems with fine manipulative ability and associated movements, however, persisted in most cases. Change in the total MND-abnormality score was also analyzed. Elevated scores and greater age at the initial assessment, and longer intervals between the initial assessment and follow-up were associated with greater improvement, indicating that biological maturation is an important factor in symptom remission. Slow background activity was the predominant EEG-pattern that tended to persist rather than to remit over time. A wide spectrum of psychiatric diagnoses was recorded on both occasions. In general, the tendency for remission of psychiatric disorders was stronger than that of persistence and new manifestation. In addition, with regard to behavioural abnormalities, the total score and subscore for emotional disorders diminished over time.

Minor neurological dysfunction after the onset of puberty: association with perinatal events

In order to study the hypotheses that puberty is related to a decrease of minor neurological dysfunction (MND) and that persisting MND is associated with perinatal factors, two groups (174 normal, 172 MND) of the Groningen Perinatal Project were followed from 12 to 14 years. At 14 years almost all the children had entered puberty ( n = 329) defined as the presence of three or more puberty signs. In the MND group 55% of the children were normal at 14 years and in 45% MND signs were still present, though in a less extensive form. The latter phenomenon was most clear in children who had just begun puberty. The effect of puberty was similar in both sexes. MND which persisted into puberty was related to neonatal neurological deviancy, lower social class, lower obstetrical optimality score and male sex. After differentiation with specific MND clusters, it appeared that fine manipulative disability was associated with neonatal neurological deviancy, with minor physical anomalies and with lower social class; choreiform dyskinesia with asphyxia; hypotonia with constitutionally related factors; and coordination problems with prematurity (< 32 weeks).

Movement Disorder Associated with Antipsychotic Drugs: The Tardive Syndromes

The term tardive dyskinesia, even when properly limited to abnormal involuntary movements occurring in individuals receiving chronic antipsychotic drugs, may still be used to refer to a range of qualitatively different motor phenomena at various body sites. Within this broad syndrome, distinct syndromes have been delineated that are phenomenologically and possibly pathophysiologically distinct. The evidence is reviewed for the existence of tardive dystonia and chronic akathisia as separate clinical entities, and for the validity of two regional subsyndromes of tardive dyskinesia, oro-facial and trunk and limb choreiform dyskinesia. Each of these tardive syndromes is discussed in terms of clinical features, pharmacological response and pathophysiology. Separate assessment of these subsyndromes is suggested in studies of tardive dyskinesia, particularly those investigating drug treatment, risk factors and natural history.

Absence of severe tardive dyskinesia in Hungarian schizophrenic out-patients.

One hundred and twenty-two patients comprising 82% of the non-hospitalized schizophrenic population of a Hungarian town were rated for tardive dyskinesia (TD). Drug histories were also obtained. No severe cases of TD were found. The markedly lower prevalence of TD in the study population in contrast to similar North American samples may be related to differences in treatment styles, in particular to: a) use of EST in place of high-dose neuroleptic therapy; b) extensive exposure to ethopropazine, promethazine, and other antiparkinson drugs. Twenty patients revealed clinically evident fine tremors, mostly of the tongue and eye-lid. Multivariate analysis revealed a positive association of choreiform dyskinesia with duration of low-potency neuroleptic treatment.

Antagonism of Levodopa by Papaverine

PAPAVERINE, the isoquinoline alkaloid, is widely employed in various formulations in the treatment of patients believed to be suffering from cerebral arteriosclerosis. Patients with Parkinson disease may thus be given papaverine preparations when symptoms are suggestive of cerebral vascular insufficiency or appear to represent instances of arteriosclerotic parkinsonism. It seems important, therefore, to call attention to an antagonistic effect of papaverine on the therapeutic response to levodopa recently observed in several patients. The clinical features of this unexpected interaction are illustrated by the first patient in which they were recognized. Report of a Case A 71-year-old woman with Parkinson disease of 20 years' duration had responded extremely well to levodopa therapy when it was started in 1968. Subsequently she enjoyed further, sustained improvement despite moderate choreiform dyskinesia on a combined regimen of levodopa and carbidopa from 1971 through May 1974. Then she began to complain of difficulty concentrating, a sense