Dystonic Reactions Research Articles

Acute pharmacogenetic dystonic reactions in a family with the CYP2D6 *41 allele: a case report

BackgroundDystonia is a known neurological complication of certain medications; however, the mechanism behind such effects is often undetermined. Similarly, the clinical pharmacogenomic effects associated with various alleles of the cytochrome P450 family of proteins, and their role in acute dystonic reactions, are also presently unknown.Case presentationWe describe a woman presenting with acute dystonic reactions to ondansetron, prochlorperazine, and metoclopramide followed by persistent focal dystonia. A similar family history was reported in her siblings and her father to prochlorperazine, drugs all metabolized by the cytochrome P450 2D6 (CYP2D6) enzyme. Pharmacogenomic testing indicated the patient was heterozygous for the intermediate metabolizer *41 allele (CYP2D6 2988G>A, NM_000106.6:c.985+39G>A, rs28371725). Her father was homozygous for this CYP2D6 *41 allele, and consequently, her siblings were obligate carriers.ConclusionsThe metabolism of ondansetron, metoclopramide, or prochlorperazine in patients with the *41 CYP2D6 allele has not been studied. In this family, clinical evidence implicates the *41 CYP2D6 allele as causing extrapyramidal adverse pharmacologic reactions. Patients with a family history of medication-induced dystonia involving these medications should be considered for pharmacogenomic testing, and patients carrying the *41 CYP2D6 allele should consider reduction or avoidance of CYP2D6-mediated medications to minimize the potential risk of adverse extrapyramidal effects.

Childhood dystonic reactions in the middle Black Sea region.

Acute dystonic reactions are a worrying reason for presentation to the pediatric emergency department and the pediatric neurology clinic in childhood. It must be diagnosed and treated quickly. The aim of this study was to examine the clinical presentations, etiological factors, and prognosis of patients presenting to our regional tertiary pediatric neurology clinic with a diagnosis of acute dystonic reactions in children.Nine pediatric patients who were treated for acute dystonic reactions between May, 2018 and May, 2020 and had adequate follow-up were included in the study. Medical record data were reviewed age, gender, etiology, features of family, treatment, and results.Three of the patients were female and 6 were male. Their average age was 11 years (4–17). All patients were evaluated as a drug-induced acute dystonic reaction. Of the 9 patients, 5 were due to metoclopramide, 3 were due to risperidone, and 1 was due to aripiprazole. It was learned that a similar situation against other drugs developed in the family history of 3 patients. As a treatment, all of them were intramuscularly applied biperiden suitable for their weight and 30 minutes dramatic improvement was observed. Additional dose had to be administered in only 1 case. All cases were discharged for 24 hours. No problem was observed in their follow-up.Drug-induced acute dystonic reaction can be diagnosed and has a clinical picture that completely resolves when effective treatment is applied. However, it should not be forgotten that it can reach life-threatening dimensions clinically.

Pisa syndrome – a case report

IntroductionPisa Syndrome or pleurothotonus is a form of dystonia and often can arise as a side effect of antipsychotic treatment conditioning high morbidity and limiting management options. Despite the fact that the precise mechanism remains unclear, a neurochemical imbalance in dopaminergic and cholinergic transmission but also in serotoninergic and noradrenergic transmission can be a possible pathophysiologic mechanism, which can lead to changes in the axial axis with abnormal posture and marked lateral trunk flexion and abnormal gait.ObjectivesRegarding a clinical case, the authors intend to review the relevant and current literature on the relationship between psychotropic drugs and Pisa Syndrome.MethodsDescription of a clinical case by consulting databases of current and scientifically relevant articles.ResultsThe clinical case reports a 48-year-old woman with a history of HIV and Substance Use Disorder, hospitalized for unspecific behavioral changes, characterized by mood changes, self-referential, persecutory and somatic delusional ideas, and delusions of the control of thought. She was medicated with antipsychotics and mood stabilizers, with subsequent development of an acute-onset dystonic condition, characterizing the Pisa Syndrome. In this context, the dose of antipsychotics was lowered and anticholinergics were introduced, with progressive improvement of the clinical picture.ConclusionsPisa Syndrome, previously seen as a rare adverse effect, can occur as a dystonic reaction related to the use of psychotropic drugs, so its use should be judicious. Further studies are needed to understand the extent of this association and its pathophysiological mechanisms in order to guide more rigorous therapeutic lines.DisclosureNo significant relationships.

Multiple antipsychotics linked to acute dystonic reactions in 7% of children

You have heard a lot about adverse effects of antipsychotics, but a recent study has found that acute dystonic reactions (ADRs) develop in only 7% of children and adolescents, and that the vast majority of these are due to poly‐prescribing.

Distonija uzrokovana metoklopramidom u službi hitne medicinske pomoći

Introduction: Metoclopramide is commonly prescribed drug for treatment of nausea and vomiting. Acute dystonic reaction is the most common adverse effect and occur at approximately 0.2% of population. Material: Data from original medical reports and the hospital discharge summary were used. Material: Retrospective study of the work of one physician in the City Institute for EMS Belgrade in the period from 2017 to 2018 involving 2481 patients. Case report: In November 2019, the parents brought a thirteen year old child in the EMS. The child had vomited for 3 days and his parents gave him 2 tablets of metoclopramide, 24h after the pill ingestion the child began to cramping. During the examination, the patient was fully consciousness and upset, with a noticeable trismus, oculogyric reaction, torticollis, tongue protrusion and dysphonia. Vital signs at admission: BP 100/60 mmHg, HR 120/minute, SpO2 98%, blood glucose level 5.6 mmol/l. ECG noted signs of sinus tachycardia. The patient was transported to the hospital, with the i.v infusion of 500ml 0.9% NaCl solution and with oxygen support of 3l/min. According to the medical documentation, the patient was hospitalized and treated with i.v. Diazepam and saline infusions. Two days after hospitalization, the patient was released home in a stable condition. Conclusion: We must be careful with an uncritically usage of metoclopramide because of possible extrapyramidal side effect. Drug induced dystonia is a potentially life-threatening condition, and it is important to recognize and timely take care of such a condition in EMS.

Drug-induced dystonia

Drug-induced dystonia (DID) is a rarely diagnosed adverse reaction to a sufficiently large number of drugs. Acute DID (ADID) occurs soon after starting to take a drug or raising its dose, and switching from one antipsychotic medication to another, especially to its injectable dosage form. Tardive DID (TDID) develops a few months or years after starting drug intake or 3 months after stopping therapy. The diagnosis of TDID is based on the persistence of dystonic hyperkinesis for more than 1 month, the use of a dopamine receptor blocking agent, and the absence of other causes of its development. The risk factors for DID are male sex; young age (less than 30 years of age); a history of dystonic reactions; hypocalcemia, alcohol use while taking the drug. DID is most commonly related to therapy with antipsychotics, metoclopramide, antidepressants, and antiepileptic drugs. The short-term use of anticholinergic drugs (benzotropin, diphenhydramine) is effective in treating ADID. Anticholinergic drugs and atypical antipsychotics (clozapine, quetiapine), benzodiazepines, muscle relaxants (baclofen), and dopamine reuptake inhibitors (tetrabenazine) are used to treat TDID. To prevent DID, it is very important that a physician should be aware of that this unwanted adverse reaction may occur and that a drug with the lowest risk for DID should be chosen.

Seizure Mimics: Oculogyric Crisis Following Metoclopramide-Video

A 9-year-old girl who experienced a seizure disorder was referred to our hospital by a medical practitioner. She presented with recurrent episodes of upward deviation of eyes with neck pain. She had taken tab metoclopramide 10 mg every 8 hours one day before for gastroenteritis. She was aware but unable to voluntarily control the attacks. On examination, she had sustained conjugate upward and lateral deviation of the eyes (oculogyric crisis), without loss of consciousness ([Fig. 1] [Video 1]). Symptoms disappeared rapidly following administration of IV promethazine 0.5 mg/kg slowly, and she remained well during follow-up 1 week later. Oculogyric crisis (OGC) is characterized by a prolonged involuntary upward deviation of the eyes. These episodes generally last for minutes, but can range from seconds to hours. Etiology includes drug-induced reactions, hereditary and sporadic movement disorders, and focal brain zdlesions. The majority of OGC cases occurred as adverse effects of neuroleptics and antiemetics. OGC usually disappears within 24 to 48 hours of drug withdrawal. Administration of anticholinergics (benztropine) or antihistamines (diphenhydramine) can alleviate OGC within minutes. The incidence of metoclopramide-induced acute dystonias is 0.2% with female preponderance.[1] A systematic review and meta-analysis revealed that the most common adverse effects following metoclopramide in children were extrapyramidal symptoms (9%), diarrhea (6%), and sedation (6%).[2] Ozel et al reported acute dystonic reaction due to metoclopramide in a 20-year-old female, which was misinterpreted as conversion disorder and seizure.[3] Acute dystonic reactions due to metoclopramide can be confused with conversion disorders, seizures and encephalitis.[1] [3] Our patient was also referred to our center by a medical practitioner on account of a presumed diagnosis of seizure disorder.

Aripiprazole-induced oculogyric crisis (acute dystonia) in 11 years old girl: a case report

Acute dystonic reaction which is described as involuntary muscle spasms and contractions including neck, chin, eye and mouth muscles is an extrapyramidal adverse effect. Acute dystonic reactions are rarely seen with atypical antipsychotics. In this study, we present a case of an aripiprazole-induced oculogyric crisis in an 11 years old girl who diagnosed with mild intellectual disability attention deficit and hyperactivity disorder, and conduct disorder. This case is important as aripiprazole-induced oculogyric crisis caused is not an expected side effect in the child and adolescent population.

Spotlight on Oculogyric Crisis: A Review.

Background:Oculogyric crisis (OGC) is a form of acute dystonia characterized by sustained dystonic, conjugate, and upward deviation of the eyes. It was initially reported in patients with postencephalitic parkinsonism. But later, other factors such as medications, movement disorders, metabolic disorders, and focal brain lesions were also found to be associated with OGC.Methods:The literature regarding OGC was searched via PubMed, Google Scholar, and through citations in relevant articles till December 2019, with keywords including OGC, oculogyric eye movements, tonic eye movement, neuroleptics and OGC, antipsychotics and OGC, and all combinations of these. Only original articles (abstract or full text) that were published in the English language were reviewed.Results:Hypodopaminergic state is implicated in the pathogenesis of OGC. Common risk factors are younger age, male sex, severe illness, high neuroleptic dose, parenteral administration of neuroleptics, high potency of neuroleptic drugs, abrupt discontinuation of anticholinergic medication, and family history of dystonia.Conclusion:OGC is an acute dystonic reaction leading to tonic upward deviation of eyes. It is associated with various neurometabolic, neurodegenerative, and movement disorders and medications such as antipsychotics, antiemetics, antidepressants, antiepileptics, and antimalarials. OGC can adversely impact the compliance and prognosis of the primary illness. Hence, it needs to be managed at earlier stages with appropriate medication, primarily anticholinergics.

Clinical profile of acute drug-induced dystonia in children

Background: Acute dystonic reactions are the most common type of extrapyramidal reactions associated with the use of certain drugs. Drug-induced dystonic reactions (DIDRs) are diagnosed based on the detailed history and physical examination. Objective: The objective of the study was to describe the clinical profile, identify the drugs causing dystonic reactions and outcomes in a cohort of children with DIDRs. Materials and Methods: This study is a prospective observational study conducted in patients with DIDRs between February 2019 and January 2020 aged <15 years. DIDRs were diagnosed on the basis of history and physical examination. Results: During the proposed study period, 12 children with DIDRs were identified with a mean age of 50.8 months and eight patients (67%) were boys. The most common cause of DIDRs was with antipsychotics in eight patients (67%) and with antiemetics in four patients (33%). All patients with DIDRs due to antiemetics were infants and received the drug with overdose. These infants needed more diagnostic investigations. Most of the children responded with stoppage of causative drug and administration of benzodiazepine and diphenhydramine. On follow-up, there was no recurrence. Conclusion: DIDRs were common with antiemetics and antipsychotics either with therapeutic dose or overdose. Benzodiazepines and diphenhydramine were more effective drugs in the treatment of DIDRs.

Dystonic Reactions Among Pediatric Patients Treated for Headache with Metoclopramide Versus Prochlorperazine (1200)

Dystonic Reactions Among Pediatric Patients Treated for Headache with Metoclopramide Versus Prochlorperazine (1200)

Frequency and Correlates of Acute Dystonic Reactions After Antipsychotic Initiation in 441 Children and Adolescents.

Objective: To determine the incidence of acute dystonic reactions (ADRs) and risk factors for ADRs in children and adolescents treated with antipsychotics. Methods: This was a retrospective chart review-based cohort study of consecutive patients who attended a university hospital's child and adolescent psychiatry department between 2015 and 2017 and who were treated with antipsychotics and had at least two follow-up visits. Results: Thirty of 441 patients (6.8%) 4-19 years of age who were treated with antipsychotics for conduct disorders (21.5%), attention-deficit/hyperactivity disorder (13.2%) and, irritability and aggression that accompanied intellectual disability (12.9%) and followed for 99.5 ± 223.3 (median: 34) days developed ADRs. ADRs developed in 11/391 patients (2.8%) treated with one antipsychotic and 19/50 patients (38.0%) treated with two antipsychotics (p < 0.001). In patients treated with one antipsychotic that developed ADRs, the time to ADRs was 4.0 ± 4.0 days after antipsychotic initiation and 2.7 ± 2.4 days after an increase in the antipsychotic dose. The time to ADRs in those treated with two antipsychotics was 3.0 ± 2.3 days after the addition of the second antipsychotic and 1.6 ± 0.8 days after a dose increase in the second antipsychotic. The incidence of ADRs during antipsychotic monotherapy was 10.5% with first-generation antipsychotics (FGAs) and 2.2% with second-generation antipsychotics (SGAs; p = 0.037). The antipsychotic was changed due to ADRs in 12/30 (40.0%) of ADR cases. Independent factors associated with ADRs were antipsychotic polypharmacy (p < 0.0001), inpatient treatment (p = 0.013), FGA use (p = 0.015), and diagnoses of schizophrenia (p = 0.039) or bipolar disorder (p < 0.0001). Conclusion: SGAs and low-potency FGA monotherapy in children and adolescents were associated with a relatively low ADR risk, whereas high- and mid-potency FGAs were associated with a high risk. Independent predictors of ADRs were antipsychotic polypharmacy, inpatient treatment, FGAs, and schizophrenia or bipolar disorder diagnoses, which may be related to more aggressive antipsychotic dosing.

Prospective study of the safety and effectiveness of droperidol in elderly patients for pre-hospital acute behavioural disturbance.

Acute behavioural disturbance in the elderly (≥65 years) is a significant issue for emergency medical services with increasing prevalence of dementia and aging populations. We investigated the pre-hospital safety and effectiveness of droperidol in the elderly with acute behavioural disturbance. This was a pre-hospital prospective observational 1-year study of elderly patients with acute behavioural disturbance. The primary outcome was proportion of adverse events (AEs) (airway intervention, oxygen saturation <90% and/or respiratory rate <12/min, systolic blood pressure <90 mmHg, sedation assessment tool score of -3 and dystonic reactions). Secondary outcomes included time to sedation, additional sedation, proportion with successful sedation. There were 149 patients (males 78 [52%], median age 78 years; 65-101 years) presenting on 162 occasions. Dementia was the commonest cause (107/164 [65%]) of acute behavioural disturbance. There were six AEs in five patients (5/162 [3%]; 95% confidence interval 1-7). Three had hypotension, one with associated hypoxia (80%); and two had respiratory AEs (respiratory rate, 10/min [no hypoxia] and hypoxia [88%] which required oxygen). Median time to sedation was 19 min (interquartile range 12-29 min). Additional sedation was given in 2/162 patients during ambulance transfer and 16/162 within an hour of hospital arrival; 24/162 (15%) failed to sedate in the ambulance; 16 subsequently settled in ED and 8/24 received additional sedation. Of 162, 123 (76%) patients successfully sedated, without AEs or additional sedation. Of 162, 114 (70%) patients received 5 mg, 46 (29%) received two doses of 5 mg and two patients (1%) received three doses. Droperidol appeared to be safe and effective for pre-hospital sedation of acute behavioural disturbance in elderly patients.

Metoclopramide-Induced Acute Dystonia: Data From a Pediatric Emergency Unit.

Metoclopramide is a commonly used medication in pediatric practice, and dystonia is a common adverse effect of it. The present study aims to evaluate the clinical characteristics of metoclopramide-induced acute dystonic reactions (MIADRs) in pediatric patients admitted to the pediatric emergency unit. Twenty-eight patients were admitted with MIADRs between June 2004 and April 2016; they were enrolled into the study retrospectively. The study group was composed of 13 females and 15 males with the mean ± SD age of the females higher than that of the males, 12.3 ± 4.5 and 7.8 ± 4.3 years, respectively. Only 9 (32.1%) of the patients were diagnosed as MIADRs at the time of admission. Seventeen patients (60.7%) received over the recommended daily dose of metoclopramide. Dystonia was focal in most of the patients, with the most affected parts consisting of the neck, eyes, and orolingual regions. In 9 of the patients, the dystonia was episodic in nature. Pharmacological treatment was used for 18 patients. No patients died, and none suffered long-term injury related to MIADRs. Metoclopramide administration may be associated with the occurrence of acute dystonic reaction. Metoclopramide-induced acute dystonic reactions may be misdiagnosed, so detailed medical history gathering and a high index of suspicion are warranted. Our data suggest that MIADRs may be dose related and that there may be age- and sex-related differences in the epidemiology of MIADRs.

Acute Dystonic Reactions in Children Treated for Headache With Prochlorperazine or Metoclopramide

BackgroundThe incidences of dystonic reactions to metoclopramide and prochlorperazine have not been well characterized in children. MethodsMedical record data were reviewed for patients at a tertiary care pediatric hospital who received metoclopramide or prochlorperazine for treatment of headache. ResultsA total of 4588 clinical encounters were identified, 2542 with prochlorperazine and 2046 with metoclopramide. One patient had a dystonic reaction with metoclopramide (0.049%). Eleven patients had a dystonic reaction with prochlorperazine (0.43%). The relative risk of a dystonic reaction with prochlorperazine over metoclopramide is 8.85 (95% confidence interval 1.15 to 68.5). There were differences between groups of patients who received metoclopramide versus prochlorperazine in terms of age, number of doses, and coadministration of diphenhydramine. In a logistic regression, administration of prochlorperazine over metoclopramide (P = 0.019) and greater number of doses (P < 0.001) remained associated with acute dystonic reactions. ConclusionsDystonic reactions are rare events among pediatric patients treated for acute headache, but are more common with prochlorperazine than metoclopramide.

Acute Necrotizing Encephalopathy Associated with Influenza A

ABSTRACT A severe and unusual complication found in children with influenza is an acute necrotizing encephalopathy. A 20-month-old female with no significant past medical history was admitted to our facility, presenting with a 4-day history of worsening fever, upper respiratory symptoms, new-onset altered mental status and episodes of extensor posturing. The initial concern was a dystonic reaction secondary to promethazine following a recent diagnosis of influenza A virus. A head computed tomography scan indicated concern for widespread edema, and the video EEG revealed focal slowing in the frontocentral regions with no epileptiform activity during episodes of extensor posturing. The first magnetic resonance imaging results were consistent with acute hemorrhagic encephalitis or severe anoxic brain injury for which there is a broad differential. A second MRI five days later found new areas of restricted diffusion that were consistent with acute necrotizing encephalitis.

Methylphenidate-Induced Oculogyric Crisis in a Patient with Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder: A Case Report

Methylphenidate is one of the agents used in the treatment of attention deficit hyperactivity disorder. In the literature, the following side effects were reported due to the use of methylphenidate: sleep and appetite problems, blood pressure and heart rate changes, headache, nervousness, crying, tics, chorea, psychosis, and rarely dystonic reaction. Acute dystonia is a well-known extrapyramidal side effect of dopamine receptor antagonists. The oculogyric crisis, a specific form of acute dystonic reaction, refers to usually upward and sometimes lateral deviation of the eyes for a certain period due to contraction of the extraocular eye muscles. Despite the increase in dopamine-related activity, psychostimulants were also reported to cause dystonic reactions rather than blocking. In this study, a patient with oculogyric crisis after the initiation of methylphenidate treatment was analyzed. Although rarely observed, dystonic reactions that may occur after methylphenidate should be considered by clinicians.

Metoclopramide-Induced Dystonic Reaction in an Infant

Metoclopramide-induced dystonic reaction (MIDR) is a clinical condition that can be seen even in all age groups even in treatment doses. A nine-month-old girl was brought to our emergency department with acute dystonic reaction that occurred after her 2.5-years-old sister gave her a 10 mg/kg metoclopramide tablet two hours before admission to the hospital. Diphenhydramine was given to the patient. One hour later, the patient’s clinical findings regressed and patient was hospitalized, and was discharged from the hospital after 66 hours without sequelae. Although metoclopramide-induced dystonic reaction is frequently reported, the number of cases under one year of age is very limited. The case presented in this report is a patient who received a higher drug dose compared to other cases reported in the literature and recovered without sequelae after follow-up. The most important factor resulting in poisoning in children is not arranging the living spaces of the children by the parents. The easiest way to prevent such cases is to educate families on this issue.

Tardive Oculogyric Crisis due to Aripiprazole treatment in an adolescent patient diagnosed with Bipolar Disorder

Antipsychotics usage in children and adolescents is becoming widespread. One of the extrapyramidal side effects associated with long-term antipsychotic drug use follow-up is an oculogyric crisis (OGC). OGC is defined as a dystonic reaction commonly observed after typical antipsychotic drug administration. However, there are rare cases which report OGC after atypical antipsychotic use. In this report, we present an adolescent with bipolar disorder who developed OGC after 2 years of aripiprazole and quetiapine use. To best of our knowledge, this case report has been the first case to present the clinical presentation of tardive OGC due to aripiprazole treatment in an adolescent patient. It is important to note that OGC might be observed in the acute phase and it might be as a result of chronic use detected during a clinical follow-up. Safety, tolerability and efficiency of aripiprazole in pediatric populations should be further analyzed in the future studies.

Drug-induced oculogyric crisis – A rare presentation to the emergency department

Oculogyric crisis (OGC) is an acute dystonic reaction of the ocular muscles characterized by the bilateral dystonic elevation of visual gaze lasting from seconds to hours. OGCs are nonepileptic eye movements and therefore should be distinguished from more commonly occurring tonic eye deviation, seen in seizure disorders, paroxysmal tonic upward gaze, and encephalopathy, commonly encountered in the emergency department. This rare neurological condition may be easily misinterpreted or overseen as functional or as an exacerbation of psychotic illness.