Extrapyramidal Research Articles

Overlap of extrapyramidal syndrome subtypes in a 47-year-old patient with metastatic rectal cancer on prochlorperazine

Overlap of extrapyramidal syndrome subtypes in a 47-year-old patient with metastatic rectal cancer on prochlorperazine

THE FIRST GENERATION AND SECOND-GENERATION ANTIPSYCHOTIC DRUGS AND THEIR PHARMACOLOGY IN TREATMENT OF SCHIZOPHRENIA

Schizophrenia is a complex and severe psychiatric disorder that affects millions of people worldwide. Antipsychotic drugs have been widely used for the treatment of schizophrenia for over 60 years. The first-generation antipsychotic drugs (FGAs) were introduced in the 1950s and revolutionized the treatment of schizophrenia. However, their use is associated with a number of adverse effects, including Extrapyramidal Symptoms (EPS) and Tardive Dyskinesia (TD). Second-generation antipsychotic drugs (SGAs), also known as atypical antipsychotics, were developed in the 1990s and have become the preferred treatment for schizophrenia due to their lower incidence of EPS and TD. They also have a broader range of therapeutic effects, such as improving negative symptoms and cognitive impairment associated with schizophrenia. This review article summarizes the pharmacology of both FGAs and SGAs, including their mechanism of action, pharmacokinetics, and adverse effects. The efficacy and safety of these drugs in the treatment of schizophrenia are also discussed. In addition, this review examines the controversy surrounding the use of SGAs and their potential metabolic side effects, such as weight gain, hyperlipidemia, and diabetes. Despite the availability of SGAs, FGAs still have a role in the treatment of schizophrenia, particularly for patients who are unresponsive to SGAs or experience intolerable side effects. Furthermore, research continues to identify new pharmacological targets and treatment strategies for schizophrenia. Understanding the pharmacology and clinical use of antipsychotic drugs is essential for optimizing the treatment of schizophrenia and improving patient outcomes.

The Management of Nausea and Vomiting in Pregnancy and Hyperemesis Gravidarum (Green-top Guideline No. 69).

An objective and validated index of nausea and vomiting such as the Pregnancy-Unique Quantification of Emesis (PUQE) and HyperEmesis Level Prediction (HELP) tools can be used to classify the severity of NVP and HG. [Grade C] Ketonuria is not an indicator of dehydration and should not be used to assess severity. [Grade A] There are safety and efficacy data for first line antiemetics such as anti (H1) histamines, phenothiazines and doxylamine/pyridoxine (Xonvea®) and they should be prescribed initially when required for NVP and HG (AppendixIII). [Grade A] There is evidence that ondansetron is safe and effective. Its use as a second line antiemetic should not be discouraged if first line antiemetics are ineffective. Women can be reassured regarding a very small increase in the absolute risk of orofacial clefting with ondansetron use in the first trimester, which should be balanced with the risks of poorly managed HG. [Grade B] Metoclopramide is safe and effective and can be used alone or in combination with other antiemetics. [Grade B] Because of the risk of extrapyramidal effects metoclopramide should be used as second-line therapy. Intravenous doses should be administered by slow bolus injection over at least 3 minutes to help minimise these. [Grade C] Women should be asked about previous adverse reactions to antiemetic therapies. If adverse reactions occur, there should be prompt cessation of the medications. [GPP] Normal saline (0.9% NaCl) with additional potassium chloride in each bag, with administration guided by daily monitoring of electrolytes, is the most appropriate intravenous hydration. [Grade C] Combinations of different drugs should be used in women who do not respond to a single antiemetic. Suggested antiemetics for UK use are given in AppendixIII. [GPP] Thiamine supplementation (either oral 100 mg tds or intravenous as part of vitamin B complex (Pabrinex®)) should be given to all women admitted with vomiting, or severely reduced dietary intake, especially before administration of dextrose or parenteral nutrition. [Grade D] All therapeutic measures should have been tried before considering termination of pregnancy. [Grade C].

Olanzapine Liquisolid Tablets Using Kolliphor EL with Improved Flowability and Bioavailability: In vitro and In vivo Characterization.

Liquisolid tablets are an innovative approach to enhance the dissolution rate and, thereby, the bioavailability of therapeutic agents with poor aqueous solubility. The objective of the current research was to compare the bioavailability of the optimized formulation of the olanzapine (OLZ) liquisolid tablet with that of the marketed tablet (MT) by conducting pharmacokinetic and behavioral assessment studies. Ten formulations were designed using Kolliphor EL as a non-volatile solvent, and the respective tablets were prepared by the direct compression method. Pre-compression studies of powders of all the formulations showed good/excellent flow properties and compressibility. The drug release profiles of liquisolid tablets were determined and compared with those of MT. Based on the in vitro results, K250 was considered as an optimized formulation and selected for further in vivo studies. AUC0-∞ value of K250 formulation was found to be 357.2 ± 35.5 ng.h.mL-1, which was higher than that of the MT (258.4 ± 29.9 ng.h.mL-1). The reduction in locomotor activity was enhanced remarkably in K250 compared with MTs at p < 0.05. The time periods taken to fall in the rotarod test were approximately equal in the experimental groups, which indicated the absence of extrapyramidal side effects. There was a remarkable decrease in the number of boxes covered in the open field test. Kolliphor EL was found to be a potential non-volatile solvent that can be used to produce liquisolid tablets of OLZ with improved flow, compressibility, dissolution, and bioavailability.

The Clinical Spectrum of ANO3-Report of a New Family and Literature Review.

Mutations in ANO3 are a rare cause of autosomal dominant isolated or combined dystonia, mainly presenting in adulthood. We extensively characterize a new, large ANO3 family with six affected carriers. The proband is a young girl who had suffered from tremor and painful dystonic movements in her right arm since the age of 11 years. She later developed a diffuse dystonic tremor and mild extrapyramidal signs (ie, rigidity and hypodiadochokinesis) in her right arm. She also suffered from psychomotor delay and learning difficulties. Repeated structural and functional neuroimaging were unremarkable. A dystonic tremor was also present in her two sisters. Her paternal aunt, father, and a third older sister presented episodic postural tremor in the arms. The father and one sister also presented learning difficulties. The heterozygous p.G6V variant in ANO3 was identified in all affected subjects. Stratification by age at onset divided ANO3 cases into two major groups, where younger patients displayed a more severe phenotype, probably due to variants near the scrambling domain. We describe the phenotype of a new ANO3 family and highlight the need for functional studies to explore the impact of ANO3 variants on its phospholipid scrambling activity.

KAJIAN PENGGUNAAN DAN EFEK SAMPING RISPERIDONE DI RUMAH SAKIT JIWA GRHASIA YOGYAKARTA

Risperidone is an atypical antipsychotic indicated for acute and chronic schizophrenia and mania. A study found that the use of risperidone as a therapy for acute schizophrenia was 25.32%. Side effects of risperidone include insomnia, anxiety, headache, and extrapyramidal symptoms. With the high use of risperidone and the many possible side effects, it is necessary to study the drug. This study aims to describe the use and side effects of risperidone at the Ghrasia Mental Hospital Yogyakarta. This research is non-experimental research using a descriptive design. Data were collected retrospectively from medical records of a patient who received risperidone prescriptions at the Grhasia Mental Hospital Yogyakarta January-December 2019. Sampling used the purposive sampling technique, and 360 samples were obtained. The incidence of side effects was analyzed using the Naranjo algorithm. The use of risperidone at the Ghrasia Mental Hospital Yogyakarta showed that patients improved 25.83%, patients improved but had to control 71.17%. The incidence of side effects was 15% of the total 360 patients taking risperidone. The most common side effects were tremor (4.72%), insomnia 2.50%, nausea 1.67%, and vomiting 1.39%. Side effects were treated with 65% additional therapy, 22% no additional therapy, and 13% drug discontinuation. Conclusion: The use of risperidone at Ghrasia Hospital Yogyakarta shows good effectiveness with a 15% incidence of side effects that are handled properly

Assessing NH300094, a novel dopamine and serotonin receptor modulator with cognitive enhancement property for treating schizophrenia.

Background: Schizophrenia is a serious psychiatric disorder that significantly affects the quality of life of patients. The objective of this study is to discover a novel antipsychotic candidate with highly antagonistic activity against both serotonin and dopamine receptors, demonstrating robust efficacy in animal models of positive, negative, and cognitive symptoms of schizophrenia. Methods: In the present study, we examined the activity of antipsychotic drug (NH300094) on 5-HT2A, 5-HT2C, 5-HT1A, 5-HT1B, 5-HT7, H1, M1, Alpha1A, D2L, D2S, Alpha2A, D3 receptor functional assay in vitro. In addition, multiple animal models, including dizocilpine (MK-801) induced hyper-locomotion; APO induced climbing; Conditioned Avoidance Response (CAR); DOI-Induced Head Twitch; Forced swimming test; Scopolamine induced cognitive impairment model, were used to verify the antipsychotic activity of NH300094 in preclinical. Results: In vitro functional assays have indicated that NH300094 is a potent antagonist of 5-HT receptors and dopamine receptors, with higher relative antagonistic activity against 5-HT2A receptor (5-HT2A IC50 = 0.47 nM) than dopamine receptors (D2L IC50 = 1.04 nM; D2S IC50 = 11.71 nM; D3 IC50 = 31.55 nM). Preclinical in vivo pharmacological study results showed that NH300094 was effective in multiple models, which is more extensive than the clinic drug Risperidone. Furthermore, the safety window for extrapyramidal side effects of NH300094 is significantly wider than that of Risperidone (For NH300094, mice catalepsy model ED50/ Mice MK-801 model ED50 = 104.6-fold; for Risperidone, mice catalepsy model ED50/ Mice MK-801 model ED50 = 12.9-fold), which suggests a potentially better clinical safety profile for NH300094. Conclusion: NH300094 is a novel potent serotonin and dopamine receptors modulator, which has good safety profile and therapeutic potential for the treatment of schizophrenia with cognition disorders.

The relationship between cognitive functioning and syndromic characteristics and neuroimaging changes in patients with different types of encephalopathies

Cognitive impairment can be a consequence of direct and indirect brain injury, hypoxia, edema, metabolic disorders, neurodegenerative processes, metabolic encephalopathies, electrolyte abnormalities, organ failure, the effects of pesticides, toxins, drugs, and infectious processes. The results are presented from the study on correlations between cognitive functioning and syndromic characteristics and neuroimaging changes in patients with chronic post-traumatic (CTE), chronic vascular (CVE), chronic alcohol-induced (CAIE) and post-infectious (PIE) encephalopathies. The data of 520 medical records of patients with CTE (n = 145), CVE (n = 145), CAIE (n = 102) and PIE (n = 128) were analyzed. Neuroimaging was performed using multislice computed tomography. Cognitive functions were examined using the Montreal Cognitive Assessment. Statistical analysis of data was carried out with the help of computer software Microsoft Excel and Statistica 13.0. There was a probable relationship between cognitive functioning and extrapyramidal syndrome in patients with CVE; cognitive impairment and emotional lability disorder in patients with CAIE; cephalalgia syndrome, motor disorder syndrome and cerebellar ataxia syndrome in patients with PIE. In participants with CTE and CAIE, there was a significant correlation between cognitive functioning and ventricular enlargement; in patients with PIE — between cognitive functioning and the enlargement of the subarachnoid spaces.

Efficacy of Long-Acting Injectable Antipsychotics Versus Oral Antipsychotics in Preventing Psychiatric Rehospitalizations.

Schizophrenia is a chronic, debilitating mental illness that incurs a large economic burden. Decreasing hospital readmissions is a priority in health care to improve patient quality of life and decrease health care costs. Determining ways to prevent readmissions such as improving access to long-acting injectable (LAI) antipsychotics is important to assess. A single-center retrospective review was conducted comparing readmission rates of patients diagnosed with schizophrenia or schizoaffective disorder discharged on LAI or oral antipsychotics between August 1, 2019, and June 30, 2022. The primary outcome was the 30-day psychiatric readmission rate. Secondary outcomes included chlorpromazine equivalent doses and use of anticholinergic medications. The 30-day readmission rate was 1.9% for the LAI antipsychotic group and 8.3% for the oral antipsychotic group ( P = 0.03; 95% confidence interval, 1.05-20.02). The average chlorpromazine equivalent antipsychotic dose of patients discharged on LAI versus oral antipsychotic medications was 477.3 and 278.6 mg/d, respectively ( P < 0.001). In addition, the prevalence of medications used to treat extrapyramidal symptom was 22.3% (n = 23) for the LAI antipsychotic group and 30.8% (n = 74) for the oral antipsychotic group ( P = 0.12). Sixty-four percent of LAI antipsychotics utilized were obtained from pharmaceutical company hospital inpatient free trial programs. Long-acting injectable antipsychotics showed a statistically significant reduction in 30-day rehospitalizations as compared with oral antipsychotics and hospital inpatient free trial programs aided in LAI antipsychotic acquisition.

Antidiarrhoeal and anti-emetic activities of aqueous leaf extract of &lt;i&gt;Ficus thonningii&lt;/i&gt; Blume in young chicks

Treatments for diarrhoeal and vomiting with modern drugs have been associated with unwanted effects such as sedation and extrapyramidal effects. In this study, Ficus thonningii Blume leaf extract (FTE) was investigated for its anti-diarrhoeal and anti-emetic properties. Two study groups, namely anti-diarrhoeal and anti-emetic groups (n=36), were sorted into: placebo; drug-treatment, and 3 plant-extract treatment (FT100, FT200 and FT300) subgroups (n = 6). In the placebo group, chicks were administered only saline solution (0.9 %) while chlorpromazine (150 mg/kg) and loperamide (2.5 mg/kg) served as positive control in the anti-emetic and antidiarrhoeal study groups, respectively. The plant-extract treatment groups (FT100, FT200 and FT300) were treated with 100, 200, and 300 mg/kg doses of FTE, respectively. Vomiting was induced using oral copper sulphate solution (50 mg/kg) and chicks were observed for latency as-well-as number of retches. In the anti-diarrhoea study group, 30 mins after treatment with extracts, diarrhoea was induced with oral castor oil and latency as-well-as number of defecation was observed. Results revealed that treatment with 200 and 300 mg/kg of FTE, similar to chlorpromazine, inhibited the number of retching in chicks by 71% and 78%, respectively. Treatment with 100, 200 and 300 mg/kg of FTE, similar to loperamide, reduced the number of droppings in chicks by 45.4%, 42.9%, and 58.4%, respectively. Thus, the results showed that FTE possess anti-emetic and anti-diarrhoeal properties which qualifies it a potential research candidate in search of new drugs.

Risperidone plasma level, and its correlation with CYP2D6 gene polymorphism, clinical response and side effects in chronic schizophrenia patients

BackgroundTo explore the influence of CYP2D6 genetic polymorphism on risperidone metabolism, thereby affecting risperidone’s effects and safeties in patients with chronic schizophrenia.MethodsSixty-nine subjects with chronic schizophrenia treated with risperidone were recruited. CYP2D6 genotypes was determined using targeted sequencing and translated into phenotype using activity system. Risperidone plasma concentrations were measured using HPLC. Positive and Negative Symptom Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) were used to evaluate the existence and severity of psychiatric symptoms, Barnes Akathisia Scale (BAS) and Extrapyramidal Symptom Rating Scale (ESRS) for neurological side effects. Metabolic and endocrine status assess were also included.ResultsThe plasma drug concentrations varied hugely among individuals. Intermediate metabolizer (IM) group had higher plasma levels of RIP and dose corrected RIP concentration, RIP/9-OH-RIP ratio and C/D ratio than normal metabolizer (NM) group (p < 0.01). There was no statistic difference between responders and non-responders in dose-adjusted plasma concentrations and ratios of RIP/9-OH-RIP and C/D. The occurrence of EPS was related to active moiety levels in 4th week (p < 0.05). The prolactin (PRL) levels in two follow-ups were both significantly higher than baseline (p < 0.01). PRL change from baseline to week 4 and week 8 were both positively associated with active moiety concentration detected in week 4 (p < 0.05).ConclusionsThe risperidone plasma levels have great inter- and intraindividual variations, and are associated with the CYP2D6 phenotypes, as well as the changes in serum prolactin in patients diagnosed with chronic schizophrenia.

Factors associated with death, hospitalization, resignation, and sick leave from work among patients with schizophrenia in Japan: a nested case–control study using a large claims database

BackgroundPremature mortality, frequent relapse that easily leads to hospitalization, and discontinuous employment are key challenges for the treatment of schizophrenia. We evaluated risk factors for important clinical outcomes (death, hospitalization, resignation, and sick leave from work) in patients with schizophrenia in Japan.MethodsA nested case–control study was conducted for patients with schizophrenia identified in a Japanese claims database. For each outcome, the case was matched with up to four controls of the same age, sex, index year, and enrollment status (employee or dependent family). Potential risk factors were defined by prescriptions or diagnoses within 3 months prior to or in the month of the event. The association among potential risk factors and each outcome was evaluated using multivariable conditional logistic regression analysis with stepwise variable selection.ResultsThe number of cases and eligible patients for each outcome were 144 and 38,451 (death), 1,520 and 35,225 (hospitalization), 811 and 18,770 (resignation), and 4,590 and 18,770 (sick leave), respectively. Depression was a risk factor for death (odds ratio [OR]: 1.92; 95% confidence interval [CI]: 1.12, 3.29), hospitalization (OR: 1.22; 95% CI: 1.05, 1.42), and sick leave from work (OR: 1.46; 95% CI: 1.36, 1.57). Other risk factors for death were hospitalization history, Charlson Comorbidity Index (CCI) score, and prescription for laxatives. Prescriptions for hypnotics, laxatives, and anticholinergics were risk factors for hospitalization. Prescriptions for hypnotics and anticholinergics were risk factors for resignation. CCI score, prescription for hypnotics, laxatives, and antidiabetics were risk factors for sick leave from work.ConclusionsOur findings suggest that depression and some physical symptoms, such as constipation and extrapyramidal symptoms, are risk factors for important clinical outcomes in patients with schizophrenia. Attention should be paid to both depression and physical symptoms for the treatment of schizophrenia.

Levofloxacin-Induced Oromandibular Dystonia in a 9-Year-Old Patient.

Extrapyramidal symptoms (EPS) that include akathisia, dystonia, pseudoparkinsonism, and dyskinesia are abnormal movements commonly induced by antipsychotic medications. These symptoms are also associated with specific non-antipsychotic agents. This case report describes a case of a 9-year-old boy on antibiotics treatment that developed EPS. A 9-year-old boy presented to the emergency department of Imam Hossein Children›s Hospital with chief complaints of trismus, difficulty speaking, and tongue protrusion. One week before these presentations, he had been prescribed Tavanex® (levofloxacin) and clindamycin. His symptoms improved after the withdrawal of antibiotics and administering Biperiden, and he was discharged in good condition. On a follow-up visit one week after discharge, no remaining symptoms were present, and he was in good condition. Based on the questions in the Naranjo criteria, levofloxacin receives a score of 7 and is a probable cause of adverse drug reaction (ADR). Clindamycin, with a score of 6, is also a probable cause for this adverse drug reaction, but clinical judgment was in favor of levofloxacin as the culprit. Clinicians should be aware of the potential EPS of levofloxacin at standard doses. Effective management of adverse events is necessary to ensure patient safety and optimal outcomes.

Extrapyramidal side effects following intravenous morphine administration in a young patient with sickle cell disease

Extrapyramidal side effects following intravenous morphine administration in a young patient with sickle cell disease

Adult Onset of Subacute Sclerosing Section Panencephalitis- A Case Report

Subacute Sclerosing Panencephalitis (SSPE) is a rare, slowly progressive disorder that affects the entire nervous system. It primarily involves the cerebral cortex, subcortex and optic nerves. Caused by a mutated strain of the measles virus, the disease is mostly irreversible and devastating. It presents with gradually progressive cognitive impairment, extrapyramidal symptoms and sometimes seizures. Although commonly seen in unvaccinated children, SSPE of adult onset is uncommon. The disease is fatal and currently has no treatment. There have been many different presentations of this disorder, ranging from optic nerve involvement to gradual cognitive decline, but none have a good prognosis; ultimately, patients may become akinetic and mute. Here, the authors present an uncommon case of SSPE occurring at an older age (26-year-old male), with a rapid and atypical presentation resembling severe post-viral syndrome, which was later diagnosed as SSPE.

Brain Volumetric changes in patients with Spinocerebellar Ataxia Type 2

Aim: Spinocerebellar ataxia type 2 (SCA2) is a trinucleotide repeat disorder characterized by mutations in the ataxin-2 gene. Although the primary symptoms of this disease are related to cerebellar involvement, such as ataxia and dysarthria, cognitive disorders associated with supratentorial involvement, depression, and extrapyramidal symptoms are also common. The aim of this study was to investigate volumetric changes in patients with SCA2. Materials and Methods: Nine SCA2 patients and sixteen age and gender-matched healthy controls were included in the study. Voxel-based morphometry (VBM) was used to explore changes in whole brain gray and white matter, while surface-based morphometry (SBM) was employed to investigate changes in cortical thickness (CT), local gyrification index (LGI), sulcal depth (SD), and fractal dimension (FD). Deep learning methods were utilized for the automatic segmentation of subcortical gray matter structures and extrapyramidal system structures. Comparisons between groups were made using GLM, T-Test, and Mann-Whitney U test. Results: VBM results showed widespread gray matter loss in the cerebellum and widespread white matter loss in the brain stem (Cluster size: 25918 voxels for gray matter, 24557 voxels for white matter). SBM findings indicated a decrease in cortical thickness (Cluster size:19276 vertices for left hemisphere; 17276 vertices for right hemisphere), more pronounced in the supratentorial frontoparietal region, while FD, LGI, and SD did not differ between groups. Volume loss was observed in the subthalamic nucleus, globus pallidus internus and externus, and red nucleus in SCA2 patients. Conclusion: SCA2 patients exhibit white and gray matter volume loss in the infratentorial region. Additionally, they show a decrease in frontoparietal cortical thickness, while FD, LGI, and SD do not show any changes. Moreover, atrophy is also observed in the extrapyramidal system structures.

Side effects of clozapine in older adults with treatment-resistant schizophrenia compared to younger adults.

To study the differences in side effects of clozapine between older adults aged ≥55years and younger adults aged 18-55years with treatment-resistant schizophrenia. A retrospective cohort study in a large mental health institute in the Netherlands. All patients diagnosed with treatment-resistant schizophrenia who started with clozapine between 2011 and 2020 (N=284) were included. We compared the number and type of side effects reported in the electronic patient files as well as the number of treatment discontinuations and the time until discontinuation, both due to side effects, of older adults versus younger adults. In the younger age group (N=183), the number of reported side effects was significantly higher in the first 3months of treatment (Mann-Whitney U=7341.5, p=0.004) and after those 3months (Mann-Whitney U=5668.5, p<0.001) compared with the number reported in the older age group (N=101). Sedation, hypersalivation, dizziness, tachycardia, heartburn, nausea, weight gain, and constipation were reported significantly more often in the younger age group, and only extrapyramidal symptoms were reported significantly more often in the older age group. There was no significant difference in the number of treatment discontinuations due to side effects (23% vs. 21.8%, Chi-2=0.051, df=1, p=0.821) and time until discontinuation due to side effects (b=0.091, SE=0.335, p=0.798) between younger and older adults. Side effects of clozapine were reported significantly less often in older patients compared with younger patients. Older patients did not discontinue treatment due to side effects more often or earlier than younger patients. Older patients with schizophrenia may not be more vulnerable to side effects than younger adults.

Acute Dystonia Associated with Low-Dose Aripiprazole in a Male Child: A Case Report

Aripiprazole is a newer anti-psychotic agent with low liability for Extrapyramidal Symptoms (EPS). Acute dystonia develops due to a lack of dopamine, resulting in a relative overactivity of cholinergic neurons. In the past, cases of Aripiprazole-induced acute dystonia have been reported more frequently among adults than children. Here, the authors present a case in which acute dystonia developed at a very low dose (2 mg) of Aripiprazole. The case involves a 10-year-old boy diagnosed with Oppositional Defiant Disorder (ODD) who exhibited aggressive behaviour and irritability. Aripiprazole (2 mg) was initiated for treatment, but after five days, the patient developed excessive sleepiness, slurred speech, oculogyric crisis, and torticollis, indicative of acute dystonia. To rule out any organic causes, a detailed assessment and investigations were conducted, including complete blood counts, liver and kidney function tests, serum calcium, electrolytes, ceruloplasmin, blood copper levels, slit-lamp examination for Kayser-Fleischer ring, and electroencephalography, which did not reveal any significant organic conditions. Aripiprazole was discontinued, and Promethazine was administered. The dystonia score on the Unified Dystonia Rating Scale (UDRS) decreased from 10 to 0 in 5 days, indicating complete resolution of dystonia. Naranjo’s causality assessment score was seven, reflecting the probable association of aripiprazole with acute dystonia. This case emphasises the importance of monitoring for adverse reactions to anti-psychotic medications, particularly in paediatric patients, and the need for prompt recognition and management of adverse effects to ensure patient safety and treatment efficacy. To the best of our knowledge, this is the first case report of acute dystonia in a child at such a low dose of Aripiprazole. Clinicians should be vigilant for the emergence of such significant adverse effects of commonly used drugs.

Evolution of Clinical, Electroencephalographic, and Radiological Changes in Sporadic Creutzfeldt–Jakob Disease

Abstract Creutzfeldt–Jakob disease (CJD) is a rare, progressive, and fatal disease. Sporadic CJD (sCJD) accounts for 85% of the CJD cases. It is characterized by rapidly progressive dementia, myoclonic jerks, and pyramidal, extrapyramidal, visual, and psychiatric symptoms. Electroencephalography (EEG) and magnetic resonance imaging (MRI) of the brain are integral to the diagnosis of the disease and show serial changes as the disease progresses. MRI brain in sCJD may be initially normal and later evolve to high-intensity signal changes in cortical, striatal, and thalamic regions on diffusion-weighted sequences and fluid-attenuated inversion recovery sequences. EEG shows evolution from the early, nonspecific slowing to the characteristic periodic sharp wave complexes (PSWC) in middle and late stages. We, hereby, report the case of a 68-year-old male who presented with rapidly progressive dementia, psychiatric symptoms, and myoclonus, whose MRI brain was initially normal and later showed diffusion restriction involving bilateral caudate, putamen, and bilateral cingulate gyrus and EEG showed evolution from diffuse slowing to typical PSWC.

The Tarnished Legacy of a Wonder Drug: Revisiting the Complicated History of Clozapine.

Anecdotal evidence of superior efficacy and lack of extrapyramidal symptoms in treating schizophrenia made clozapine a promising therapy in the United States during the early 1970s. In 1975, however, numerous fatal cases of clozapine-related agranulocytosis in Finland nearly ended the drug's development. Convinced of the significant benefits to patients, some clinicians in the United States advocated having clozapine available on a case-by-case humanitarian basis, which eventually helped resurrect the drug for Food and Drug Administration approval in 1989. This article builds on previous literature by utilizing oral histories from clinicians, researchers, and a patient's family member to understand how clozapine was saved. Exploring these stakeholders' perspectives has value to modern clinicians, who underprescribe the drug despite demonstrable benefits for treatment-resistant schizophrenia and suicide prevention.