Choreoathetoid Movements Research Articles

Massive fatal overdose of abrin with progressive encephalopathy

Introduction: The jequirity bean (Abrus precatorius) seed contains abrin, a toxalbumin, that irreversibly binds the 60-s ribosomal subunit inhibiting protein synthesis. Neurologic manifestations of ingestions are rare.Case details: We present a case of a 20-year-old man with 24 h of vomiting, diarrhea and 2 h of hematemesis and hematochezia. He admitted to purchasing 1000 jequirity beans online, crushing and ingesting them 26 h prior to presentation in a suicide attempt. Over the next 2 days, he developed hallucinations, incomprehensible mumbling and grunting, disconjugate gaze with abnormal roving eye movements and a left gaze preference with his right eye deviated medially. There was a fine tremor of the upper extremities and he had brief episodes of choreoathetoid movements of his legs. A head CT was normal with no cerebral edema. He progressed to minimally responsive to noxious stimuli, and was unable to converse or follow commands and displayed increased choreoathetoid movements of his extremities. An electroencephalogram (EEG) showed only mild background slowing. Magnetic resonance imaging (MRI) was performed showing bilaterally symmetric signal abnormalities in the basal ganglia, brainstem, corpus callosum and corona radiata with diffuse leptomeningeal enhancement. The patient developed a tonic–clonic seizure followed by pulseless electrical activity, from which he was resuscitated. He was provided comfort care and died just under 5 days after his ingestion.Results: Urine analysis using liquid chromatography coupled to tandem mass spectrometry was positive for 8.84 ng/ml of l-abrine (4.96 ng l-abrine/mg creatinine) 61 h after admission to the hospital (approximately 87 h post-ingestion). Serum concentrations for l-abrine and ricinine were both below the limits of detection.Discussion: Ingestion of 1000 crushed jequirity beans purchased on the internet resulted in progressive encephalopathy and death.

Cerebral folate deficiency: Analytical tests and differential diagnosis.

Cerebral folate deficiency is typically defined as a deficiency of the major folate species 5-methyltetrahydrofolate in the cerebrospinal fluid (CSF) in the presence of normal peripheral total folate levels. However, it should be noted that cerebral folate deficiency is also often used to describe conditions where CSF 5-MTHF is low, in the presence of low or undefined peripheral folate levels. Known defects of folate transport are deficiency of the proton coupled folate transporter, associated with systemic as well as cerebral folate deficiency, and deficiency of the folate receptor alpha, leading to an isolated cerebral folate deficiency associated with intractable seizures, developmental delay and/or regression, progressive ataxia and choreoathetoid movement disorders. Inborn errors of folate metabolism include deficiencies of the enzymes methylenetetrahydrofolate reductase, dihydrofolate reductase and 5,10-methenyltetrahydrofolate synthetase. Cerebral folate deficiency is potentially a treatable condition and so prompt recognition of these inborn errors and initiation of appropriate therapy is of paramount importance. Secondary cerebral folate deficiency may be observed in other inherited metabolic diseases, including disorders of the mitochondrial oxidative phosphorylation system, serine deficiency, and pyridoxine dependent epilepsy. Other secondary causes of cerebral folate deficiency include the effects of drugs, immune response activation, toxic insults and oxidative stress. This review describes the absorption, transport and metabolism of folate within the body; analytical methods to measure folate species in blood, plasma and CSF; inherited and acquired causes of cerebral folate deficiency; and possible treatment options in those patients found to have cerebral folate deficiency.

Tardive Dyskinesia: New Treatments Available.

Tardive dyskinesia (TD), the choreoathetoid movements of fingers, arms, legs, and trunk and irregular stereotypical movements of the mouth, face, and tongue, has been the scourge of antipsychotic medications since the approval of chlorpromazine. TD tends to occur late in treatment and sometimes remains after discontinuation of the antipsychotic medication. With the recent approval of two medications, valbenazine (Ingrezza®) and deutetrabenazine (Austedo®), there are now treatments for this disfiguring consequence of dopamine-blocking medications. The current article distinguishes the movement disorder adverse effects of dopamine antagonists, explains the putative mechanism of action, and describes how best to treat TD with the new vesicular monamine transporter 2 (VMAT2) medications now approved by the U.S. Food and Drug Administration. [Journal of Psychosocial Nursing and Mental Health Services, 57(5), 11-14.].

Choreoathetoid movements associated with methamphetamine: A case report and review of literature.

Physicians and psychiatrists often encounter patients in the emergency department presenting after methamphetamine use. While physical and psychiatric manifestations associated with methamphetamine use are well known, movement disorders are relatively less common. The aim of this case report is to add to existing literature awareness about the possibility of movement disorders occurring after methamphetamine use, discuss the possible mechanism by which such use leads to dyskinesia, and describe possible management strategies. In this case report, we describe choreoathetoid movements occurring in a young female after relatively short-term methamphetamine use. Evidence for treatment of methamphetamine induced choreoathetosis is limited. Expectant management of such symptoms is a viable option if there are no additional comorbidities that require therapy. Clinicians should be alert to the possibility of movement disorders in methamphetamine users and familiar with treatment options. (Am J Addict 2018;XX:1-4).

Effect of Risperidone on the Motor and Functional Disability in Children With Choreoathetoid Cerebral Palsy

BackgroundTherapeutic options for management of choreoathetoid cerebral palsy, which is a permanent disorder, are limited. Available medications either have significant side effects or are unsuitable for long-term use. Risperidone has shown promise in the management of chorea and has been found to be safe in children less than five years. MethodsChildren with choreoathetoid cerebral palsy were enrolled after parental consent and given risperidone for six-month period along with standard care. The choreoathetoid movements were assessed using Abnormal Involuntary Movement Scale, the upper-limb functions were assessed using Quality of upper extremity skill tests, and the quality of life using Cerebral palsy-Quality of life. Side effects were monitored clinically, by biochemical tests and electrocardiogram. ResultsOf 42 children with choreoathetoid cerebral palsy who were screened over a period of one year, 35 subjects meeting the study criteria were enrolled. Thirty children completed six months of risperidone therapy, the remaining five subjects were excluded because of time missed due to intercurrent unrelated illnesses. Data of these 30 children were analyzed as per per-protocol analysis. Their mean age was 6.35 ± 3.17 years. Abnormal movements showed statistically significant decline after risperidone (19.7 vs 14.7, P < 0.0001). Functional ability of upper limbs and quality of life also showed improvement (37.0 vs 43.8, P < 0.0001 and 64.3 vs 70.0, P < 0.0001, respectively) after six months of risperidone therapy. Positive change in the behavior was also noted. It was well tolerated without significant side effects. ConclusionRisperidone is a promising drug to manage children with choreoathetoid cerebral palsy and is well tolerated in children.

Encefalite autoimune anti recetor N-metil D-aspartato: relato de dois casos

AIMS: To report two cases with different presentations of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, a newly identified autoimmune disease characterized by consciousness changes, memory deficit, seizures, autonomic dysfunction and movement disorders.CASES DESCRIPTION: A six-year-old female, who presented with dystonic and choreoathetoid movements with refusal to walk. A 17-year-old male, presented with behavioral changes, retrograde amnesia and seizures. Electroencephalogram and brain magnetic resonance imaging did not show any significant findings. Anti-NMDAR antibodies were positive in cerebrospinal fluid in both cases and in serum in the first patient. Methylprednisolone, immunoglobulin and rituximab were given at different intervals. Both had a recurrence about six months later, with recovery at the end of one and a half year of the diagnosis.CONCLUSIONS: Anti-NMDAR encephalitis should be considered in patients with sudden onset of neuropsychiatric symptoms. Early diagnosis and treatment are major prognostic factors.

Further Delineation of the Clinical Phenotype of Cerebellar Ataxia, Mental Retardation, and Disequilibrium Syndrome Type 4.

Background:Cerebellar ataxia, mental retardation, and disequilibrium syndrome (CAMRQ) is a heterogeneous group of genetic disorders that have been grouped by shared clinical features; all of these features are transmitted via an autosomal recessive mechanism. Four variants of this syndrome have been identified so far, and each one differs in terms of both clinical and genotypical features. CAMRQ4 is a rare genetic disorder characterized by mental retardation, ataxia or an inability to walk, dysarthria and, in some patients, quadrupedal gait.Methods:We investigated three Saudi families with CAMRQ4. Blood samples were collected from the affected patients, their parents, and healthy siblings. DNA was extracted from whole blood, and whole-exome sequencing was performed. Findings were confirmed by segregation analysis, which was performed on other family members.Results:Thus far, 17 patients have been affected by CAMRQ4. Genetic analysis of all patients, including our current patients, showed a mutation in the aminophospholipid transporter, class I, type 8A, member 2 gene (ATP8A2). A series of common phenotypical features have been reported in these patients, with few exceptions. Ataxia, mental retardation, and hypotonia were present in all patients, consanguinity in 90% and abnormal movements in 50%. Moreover, 40% achieved ambulation at least once in their lifetime, 40% had microcephaly, whereas 30% were mute. Magnetic resonance imaging (MRI) of the brain was normal in 60% of patients.Conclusions:We described the largest cohort of patients with CAMRQ4 syndrome and identified three novel mutations. CAMRQ4 syndrome should be suspected in patients presenting with ataxia, intellectual disability, hypotonia, microcephaly, choreoathetoid movements, ophthalmoplegia, and global developmental delay, even if brain MRI appears normal.

Clinical heterogeneity of glycine encephalopathy in three Palestinian siblings: A novel mutation in the glycine decarboxylase (GLDC) gene

IntroductionGlycine encephalopathy (GE), also known as non-ketotic hyperglycinemia (NKH), is a rare inborn error of glycine metabolism caused by a defect in glycine cleavage system, a multi-enzyme complex located in mitochondrial membrane. This defect results in elevated glycine concentration in plasma and cerebrospinal fluid (CSF). Clinical manifestations vary from severe lethargy, hypoactivity and apneic episodes in the neonatal form, mild or moderate psychomotor delay and seizures in the infantile form, and abnormal behaviors, ataxia and choreoathetoid movements in late onset form. More than 50 GLDC mutations were found, reflecting large heterogeneity of the gene. MethodsWe describe the clinical, biochemical and molecular characteristics of three Palestinian siblings who have distinct clinical phenotypes. Molecular study was performed utilizing standard Polymerase Chain Reaction (PCR) amplification then direct DNA sequencing for the affected family members. ResultsTheir phenotypes included severe symptoms in neonatal period, infantile onset of seizure and psychomotor delay and a mild late-onset form with speech delay at age 20months. All siblings were homozygous for a novel mutation Y164H in exon 4 of GLDC gene. The described novel homozygous variant in our study is predicted deleterious and pathogenic. ConclusionsThis article further expands the genetic spectrum of glycine encephalopathy and adds an evidence of the clinical heterogeneity of glycine encephalopathy even in siblings with identical mutation.

A further case of brain-lung-thyroid syndrome with deletion proximal to NKX2-1

Brain-lung-thyroid syndrome (OMIM #610978) is associated with mutations in the NK2 homeobox 1 (NKX2-1) gene, a transcription factor important in development. 50% of patients are affected by the full triad, comprising congenital hypothyroidism, benign hereditary chorea and infant respiratory distress syndrome. Four cases have previously been reported where a patient has features consistent with brain-lung-thyroid syndrome and a chromosome 14q13 deletion adjacent to, but not disrupting, NKX2-1. We present a patient who has a phenotype consistent with brain-lung-thyroid syndrome, featuring congenital hypothyroidism and choreoathetoid movements with gross motor delay. Thyroid ultrasound showed a small-normal gland and spontaneous resolution of hypothyroidism. Array CGH revealed a de novo 14q13.2–3 deletion adjacent to but not directly involving NKX2-1. Sequencing of NKX2-1 was normal. This report highlights a further case of chromosomal deletion adjacent to NXK2-1 in a patient with a phenotype consistent with brain-lung-thyroid syndrome, and confirms that array-CGH is a useful test in the investigation of congenital hypothyroidism. Deletion of the adjacent gene MBIP in most reported cases so far may be relevant to the pathogenesis of brain-lung-thyroid syndrome. Deletion of nearby promoter or enhancer elements acting on NKX2-1 could also be an important factor. However, further work is needed to elucidate the pathogenesis of the brain-lung-thyroid phenotype in such cases.

ALG13-CDG with Infantile Spasms in a Male Patient Due to a De Novo ALG13 Gene Mutation.

A boy presented at the age of 3.5 months with a developmental delay. He developed infantile spasms with hypsarrhytmia on EEG 1 month later. Additional symptoms were delayed visual development, asymmetrical hearing loss, hypotonia, and choreoathetoid movements. He also had some dysmorphic features and was vulnerable for infections. He was treated successively with vigabatrin, prednisolone, valproic acid, nitrazepam, and lamotrigine without a lasting clinical effect, but showed a treatment response to levetiracetam. Cerebral MRI showed hypoplasia of the corpus callosum and a mild delay in myelination. Further investigations including metabolic screening and glycosylation studies by transferrin isoelectric focusing were all considered to be normal. Whole-exome sequencing identified a de novo mutation in the ALG13 gene (c.320A>G, p.(Asn107Ser)). Mutations in this gene, which is located on the X-chromosome, are associated with congenital disorders of glycosylation type I (CDG-I). Mass spectrometric analysis of transferrin showed minor glycosylation abnormalities. The c.320A>G mutation in ALG13 has until now only been described in girls and was thought to be lethal for boys. All girls with this specific mutation presented with a similar phenotype of developmental delay and severe early onset epilepsy. In two girls glycosylation studies were performed which showed a normal glycosylation pattern. This is the first boy presenting with an epileptic encephalopathy caused by the c.320A>G mutation in the ALG13 gene. Since glycosylation studies are near-normal in patients with this mutation, the diagnosis of ALG13-CDG can be missed if genetic studies are not performed.

SSRI Facilitated Crack Dancing

Choreoathetoid movement secondary to cocaine use is a well-documented phenomenon better known as “crack dancing.” It consists of uncontrolled writhing movements secondary to excess dopamine from cocaine use. We present a 32-year-old male who had been using cocaine for many years and was recently started on paroxetine, a selective serotonin reuptake inhibitor (SSRI) for worsening depression four weeks before presentation. He had been doing cocaine every 2 weeks for the last three years and had never “crack danced” before this episode. The authors have conducted a thorough literature review and cited studies that suggest “crack dancing” is associated with excess dopamine. There has never been a documented case report of an SSRI being linked with “crack dancing.” The authors propose that the excess dopaminergic effect of the SSRI lowered the dopamine threshold for “crack dancing.” There is a communication with the Raphe Nucleus and the Substantia Nigra, which explains how the SSRI increases dopamine levels. This is the first documented case of an SSRI facilitating the “crack dance.”

T43 - Genome-Wide Association Of Tardive Dyskinesia: Preliminary Findings

Background Tardive dyskinesia (TD) is a movement disorder manifested as involuntary movement of orofacial muscles or choreoathetoid movements of trunk and limbs. Commonly observed in schizophrenia, TD is potentially a persistent and irreversible condition associated with sustained antipsychotic treatment. While various theories have been put forth, the pathophysiology of TD is still unclear, with no well-accepted treatment. The occurrence of TD in only some patients appears to suggest possible individual genetic susceptibly. Recent genome-wide association studies (GWAS) have identified several candidate genes such as the GLI2 and HSPG2, however, none of these candidate genes were identical to those from candidate gene studies. Here, we performed a GWAS on TD schizophrenia patients of Chinese ethnicity. Methods The sample consisted of 842 schizophrenia patients of Chinese ethnicity, recruited from the Institute of Mental Health Singapore. Diagnosis of schizophrenia was ascertained on the Structured Clinical Interview for DSM-IV, and dyskinesia was rated on the Abnormal Involuntary Movement Scale (AIMS). Genotyping was performed using the Illumina 1M Duo Beadchip. Standard GWAS QC procedures were carried out. QC-ed markers were phased with SHAPEIT and imputed via Minimac3 (MACH) to the 1000 Genomes Project Phase 3 reference panel (GRch37). Subsequent association tests were conducted on PLINK2. Results None of the markers reached genome-wide significance. One-hundred top SNPs (top SNP: rs55823922, Rsq = 0.999, MAF = 0.241, Beta = 0.244, SE= 0.0485, p = 6.323x10-07) were identified. The genes in closest proximity to top SNPs are P2RY1 (purinergic receptor P2Y1), RAP2B (RAS protein 2B) and MBNL1 (Muscleblind like splicing regulator 1). Discussion None of the genes associated with TD were implicated in psychiatric conditions. The purinergic receptor 1 protein functions as a receptor for extracellular adenine nucleotides, and mediates adenosine diphosphate (ADP) induced intracellular calcium mobilisation in platelet binding; it is implicated in Alzheimer’s disease. The RAP2B is involved in cell growth, differentiation, and apoptosis, and is implicated in the Epidermal Growth Factor Receptor and Cholinergic Signalling pathways. MBNL1 is a member of the muscleblind protein family which has been implicated in myotonic dystrophy, a condition characterised by muscle abnormalities and muscle wasting. These susceptibility genes appear to be involved in neurodegenerative conditions, and are congruent with the neurodegenerative theory of TD. Further replication is warranted.

The use of tetrabenazine for the treatment of drug-induced tardive dyskinesia – report of four cases

Tardive dyskinesias are defined as a syndrome of involuntary, irregular, hyperkinetic movement disorders, including mixed movement disorders of the face and the mouth as well as choreoathetoid movements of the trunk and limbs. They are a serious and usually irreversible side effect of chronic neuroleptic treatment and affect approximately 15–20% of patients. Treatment attempts using amantadine, levetiracetam, piracetam, clonazepam, propranolol, vitamin B6, vitamin E, ondansetron, botulinum toxin and Ginkgo biloba were made. However, in many cases the treatment efficacy has not been confirmed in long-term studies in larger groups of patients. Tetrabenazine, registered in Poland for the treatment of hyperkinetic motor disorders in the Huntington’s disease, is one of the available therapeutic options. We present the course and the effects of tetrabenazine therapy in four patients with antipsychotic-induced tardive dyskinesias. Based on the experience gained during the research program using tetrabenazine, we believe that the use of this agent should be limited to patients in a stable mental condition, with no current symptoms of depression or active psychotic symptoms. In our opinion, suicidal tendencies or thoughts and a history of neuroleptic malignant syndrome are absolute contraindications. The off-label use of tetrabenazine requires a written informed consent of the patient and careful monitoring of their mental and neurological condition.

Huntington`s Chorea - a Case Report and review of literature

A 45 years old gentleman presented to Medical Clinic of Naval Hospital (PNS Hafeez) Islamabad in January 2001 with choreform movements of the body and early dementia of six months duration. He had a strong family history of similar disease, which included his father and two brothers. On neurological examination he had choreoathetoid movements and features of early dementia. His chest was clinically clear and examination of heart and abdomen was normal. Eye examination did not reveal any evidence of Kayser-Fleischer rings (seen in Wilson`s disease). Laboratory investigations showed haemoglobin 13.8 Gm/dl, WBC 7.7 x10e9/L, serum urea 32 mg/dl, serum sodium 139 mmol/L serum potassium 3.8 mmol/L, ASO titre less than 200 IU/ml, serum bilirubin 6 umol/L, ALT 102 U/L, serum alkaline phosphatase 155 U/L, serum caeruloplasmin 42 mg/dl and serum copper 164 mmol/L (WNL). X-ray chest was normal and CT scan brain showed early generalized cerebral atrophy. He was managed with haloperidol (0.5mg) 12 hourly, Procyclidine (kemadrin, 5mg) 8 hourly and Propranolol (Inderal 10mg) 8 hourly. He was discharged from hospital with relative improvement after 2 weeks.

Cervical demyelinating lesion presenting with choreoathetoid movements and dystonia

Pseudoathetosis and dystonia are rare manifestations of spinal cord disease that have been already reported in lesions involving the posterior columns at the cervical level. We report two patients with a cervical demyelinating lesion at C3–C4 level presenting with hand dystonia and pseudoathetoid movements. The movement disorder disappeared after steroid treatment.The cases we described highlight the importance of identifying secondary causes of movement disorders that can be reversible with appropriate therapy.

Paroxysmal dyskinesia on waking: two case reports

Until recently, paroxysmal hypnogenic dyskinesia was thought to be a rare movement disorder characterized by intermittent dystonia and/or choreoathetoid movements that occur during non-rapid eye movement sleep, with consciousness preserved once the patient is awakened during the episodes. Recent investigations have revealed that most, but not all, paroxysmal hypnogenic dyskinesia cases are actually frontal lobe epilepsy. Here, we present two cases with paroxysmal choreoathetoid movements on waking during non-rapid eye movement sleep. Although they did not respond to antiepileptic drugs, they did respond to antidopaminergic drugs. This supports the opinion that non-epileptic paroxysmal hypnogenic dyskinesia does exist.

Acute Chorea Onset after Hot Food Consumption in a Patient with Moyamoya Disease.

Acute Chorea Onset after Hot Food Consumption in a Patient with Moyamoya Disease.

A young child of anti-NMDA receptor encephalitis presenting with epilepsia partialis continua: the first pediatric case in Korea.

Anti-N-methyl D-aspartate receptor (anti-NMDAR) encephalitis, recently recognized as a form of paraneoplastic encephalitis, is characterized by a prodromal phase of unspecific illness with fever that resembles a viral disease. The prodromal phase is followed by seizures, disturbed consciousness, psychiatric features, prominent abnormal movements, and autonomic imbalance. Here, we report a case of anti-NMDAR encephalitis with initial symptoms of epilepsia partialis continua in the absence of tumor. Briefly, a 3-year-old girl was admitted to the hospital due to right-sided, complex partial seizures without preceding febrile illness. The seizures evolved into epilepsia partialis continua and were accompanied by epileptiform discharges from the left frontal area. Three weeks after admission, the patient's seizures were reduced with antiepileptic drugs; however, she developed sleep disturbances, cognitive decline, noticeable oro-lingual-facial dyskinesia, and choreoathetoid movements. Anti-NMDAR encephalitis was confirmed by positive detection of NMDAR antibodies in the patient's serum and cerebrospinal fluid, and her condition slowly improved with immunoglobulin, methylprednisolone, and rituximab. At present, the patient is no longer taking multiple antiepileptic or antihypertensive drugs. Moreover, the patient showed gradual improvement of motor and cognitive function. This case serves as an example that a diagnosis of anti-NMDAR encephalitis should be considered when children with uncontrolled seizures develop dyskinesias without evidence of malignant tumor. In these cases, aggressive immunotherapies are needed to improve the outcome of anti-NMDAR encephalitis.

Clinical manifestations of 5 patients with idiopathic paroxysmal kinesigenic choreoathetosis

Paroxysmal kinesigenic choreoathetosis (PKC) is a rare disorder characterized by recurrent and brief attacks of choreoathetoid and/or dystonic movements in trunk and limbs triggered by initiation of voluntary movement. Of 5 patients with idiopathic PKC in our hospital, four were men and one was with family history. Age of onset ranged from 8 to 15 years old. They were consistent with previous reports in the characteristics of involuntary movements, normal neurological findings, normal laboratory data, no abnormal findings of standard imaging studies, and good restraining effects on attacks with carbamazepine. Individual body parts where attacks often involved were different among 5 patients. Although previous reports which said the prognosis and outcome of PKC were good, neuropsychological examinations in our study revealed that 2 patients out of 5 had certain cortical dysfunction, one patient was with progressive deterioration, and the other was with underlying mild abnormalities. Detailed and serial neuropsychological examinations might be necessary for some PKC patients.

Leigh's disease (subacute necrotising encephalo myelopathy): a rare mitochondrial disorder

Leigh syndrome is a rare progressive neurodegenerative, mitochondrial disorder of childhood with only a few cases documented from India. Raised lactate levels in blood and/or cerebrospinal fluid along with neuroimaging, mainly the Magnetic Resonance Imaging showing characteristic symmetrical necrotic lesions in the basal ganglia and/or brain stem confirms the diagnosis. MRS can also be used to detect raised level of Lactate. Here, we report a case of 11 months old female child who presented with seizures, delayed milestones and regression of the already achieved milestones with abnormal choreoathetoid movements and dystonia.