Extrapyramidal Research Articles

Efficacy, acceptability and tolerability of second-generation antipsychotics for behavioural and psychological symptoms of dementia: a systematic review and network meta-analysis

BackgroundBehavioural and psychological symptoms of dementia (BPSD) are highly prevalent in people living with dementia. Second-generation antipsychotics (SGAs) are commonly used to treat BPSD, but their comparative efficacy and acceptability...

Transition to end-of-life care in patients with neurological diseases in an acute hospital ward

BackgroundTransitioning to end-of-life care and thereby changing the focus of treatment directives from life-sustaining treatment to comfort care is important for neurological patients in advanced stages. Late transition to end-of-life care for neurological patients has been described previously.ObjectiveTo investigate whether previous treatment directives, primary medical diagnoses, and demographic factors predict the transition to end-of-life care and time to eventual death in patients with neurological diseases in an acute hospital setting.MethodAll consecutive health records of patients diagnosed with stroke, amyotrophic lateral sclerosis (ALS), and Parkinson’s disease or other extrapyramidal diseases (PDoed), who died in an acute neurological ward between January 2011 and August 2020 were retrieved retrospectively. Descriptive statistics and multivariate Cox regression were used to examine the timing of treatment directives and death in relation to medical diagnosis, age, gender, and marital status.ResultsA total of 271 records were involved in the analysis. Patients in all diagnostic categories had a treatment directive for end-of-life care, with patients with haemorrhagic stroke having the highest (92%) and patients with PDoed the lowest (73%) proportion. Cox regression identified that the likelihood of end-of-life care decision-making was related to advancing age (HR = 1.02, 95% CI: 1.007–1.039, P = 0.005), ischaemic stroke (HR = 1.64, 95% CI: 1.034–2.618, P = 0.036) and haemorrhagic stroke (HR = 2.04, 95% CI: 1.219–3.423, P = 0.007) diagnoses. End-of-life care decision occurred from four to twenty-two days after hospital admission. The time from end-of-life care decision to death was a median of two days. Treatment directives, demographic factors, and diagnostic categories did not increase the likelihood of death following an end-of-life care decision.ConclusionsResults show not only that neurological patients transit late to end-of-life care but that the timeframe of the decision differs between patients with acute neurological diseases and those with progressive neurological diseases, highlighting the particular significance of the short timeframe of patients with the progressive neurological diseases ALS and PDoed. Different trajectories of patients with neurological diseases at end-of-life should be further explored and clinical guidelines expanded to embrace the high diversity in neurological patients.

Kufor-Rakeb syndrome-associated psychosis: a novel loss-of-function ATP13A2 variant and response to antipsychotic therapy

Biallelic (autosomal recessive) pathogenic variants in ATP13A2 cause a form of juvenile-onset parkinsonism, termed Kufor-Rakeb syndrome. In addition to motor symptoms, a variety of other neurological and psychiatric symptoms may occur in affected individuals, including supranuclear gaze palsy and cognitive decline. Although psychotic symptoms are often reported, response to antipsychotic therapy is not well described in previous case reports/series. As such, we describe treatment response in an individual with Kufor-Rakeb syndrome-associated psychosis. His disease was caused by a homozygous novel loss-of-function ATP13A2 variant (NM_022089.4, c.1970_1975del) that was characterized in this study. Our patient exhibited a good response to quetiapine monotherapy, which he has so far tolerated well. We also reviewed the literature and summarized all previous descriptions of antipsychotic treatment response. Although its use has infrequently been described in Kufor-Rakeb syndrome, quetiapine is commonly used in other degenerative parkinsonian disorders, given its lower propensity to cause extrapyramidal symptoms. As such, quetiapine should be considered in the treatment of Kufor-Rakeb syndrome-associated psychosis when antipsychotic therapy is deemed necessary.

Therapeutic Dose of Metoclopramide Induced Dystonic Reacton in Children

Metoclopramide is a dopamine antagonist that is used in gastro esophageal disease and enteritis in adults and pediatric. The major side effects are extrapyramidal symptoms. They appear as dystonic movements. These are more common in children and young adults, especially in females. This retrospective descriptive study was conducted in Misurata Medical Center. It is aimed to draw attention to the frequent occurrence of metoclopramide-induced side-reactions. We studied the files of 45 patients who had been exposed to this reaction between the years of 2006 to 2008. Different dosage form of metoclopramide found to induced this acute reaction. Dystonia was occurred in 18 (40%) children who received drops, 10 (22%) patients received injection, and 6 (13.33%) children received syrup, while one patient received a tablet. The other children had received two dosage forms as injection with drops, syrup or suppository. All 45 children were treated intravenously with a single dose of diazepam. Young children especially females are more susceptible to dystonic reactions form metoclopramide. Our study indicates that diazepam is effective drug to abolish this adverse reaction.

Comparative efficacy and safety of olanzapine and risperidone in the treatment of psychiatric and behavioral symptoms of Alzheimer's disease: Systematic review and meta-analysis.

Olanzapine and risperidone have emerged as the most widely used drugs as short-term prescription in the treatment of behavioral disturbances in dementia. The present systematic review and meta-analysis was hence performed to investigate the effectiveness and safety profile of olanzapine and risperidone in the treatment of behavioral and psychological symptoms of dementia (BPSD), aiming to provide updated suggestion for clinical physicians and caregivers. Prospective controlled clinical studies were included, of which available data was extracted. Outcomes of BEHAVE-AD scores with the variation of grades, specific behaviors variables, as well as safety signals were pooled for the analysis by odds rates and weighted mean differences, respectively. Medline, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and WanFang. Prospective, controlled clinical studies, conducted to compare the effectiveness and safety profile of olanzapine and risperidone in the treatment of BPSD. Interested data including baseline characteristics and necessary outcomes from the included studies were extracted independently by 2 investigators. BEHAVE-AD scale was adopted to assess the efficacy in the present study. All behaviors were evaluated at the time of the initiation of the treatment, as well as the completion of drugs courses. Adverse events were assessed with the criteria of Treatment Emergent Symptom Scale, or Coding Symbols for a Thesaurus of Adverse Reaction Terms dictionary. Weighted mean difference was used for the pooled analysis. A total of 2427 participants were included in the present meta-analysis. Comparative OR on response rate, and remarkable response rate between olanzapine and risperidone was 0.65 (95% CI: 0.51-0.84; P = .0008), and 0.62 (95% CI: 0.50-0.78; P < .0001), respectively. There were statistical differences observed by olanzapine on the improvement of variables including delusions (WMD, -1.83, 95% CI, -3.20, -0.47), and nighttime behavior disturbances (WMD, -1.99, 95% CI, -3.60, -0.38) when compared to risperidone. Our results suggested that olanzapine might be statistically superior to risperidone on the reduction of BPSD of Alzheimer's disease, especially in the relief of delusions and nighttime behavior disturbances. In addition, olanzapine was shown statistically lower risks of agitation, sleep disturbance, and extrapyramidal signs.

Exploring the interplay of psychiatric symptoms, antipsychotic medications, side effects, employment status, and quality of life in Chronic Schizophrenia

BackgroundMany factors contribute to quality of life (QoL) in patients with schizophrenia, yet limited research examined these factors in patients in China. This cross-sectional study explores subjective QoL and its associated factors in patients.MethodsThe QoL was assessed using the Schizophrenia Quality of Life Scale (SQLS). Clinical symptoms were evaluated using the Brief Psychiatric Rating Scale (BPRS) and seven factors were extracted. Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder Scale (GAD-7) were used to assess depression and anxiety. Cognitive impairment was assessed using the Ascertain Dementia 8 (AD8). The Treatment Emergent Symptom Scale (TESS) and Rating Scale for Extrapyramidal Side Effects (RSESE) were used to evaluate the side effects of medications.ResultsWe recruited 270 patients (male:142,52.6%, mean age:41.9 ± 9.4 years). Positive correlations were observed between SQLS and its subdomains with the total score of BPRS, PHQ-9, GAD-7, AD8, TESS, and RSESE (all P < 0.005). Patients who were taking activating second-generation antipsychotics (SGAs) had lower scores on total SQLS, Motivation/ Energy domain of SQLS (SQLS-ME) as well as Symptoms/ Side effects domain of SQLS (SQLS-SS) compared to those taking non-activating SGAs (all P < 0.005). Multiple regression analysis showed that depressive/ anxiety symptoms and cognitive impairment had significant negative effects on QoL (P ≤ 0.001), while activating SGAs had a positive effect (P < 0.005). Blunted affect and unemployment were inversely associated with the motivation/energy domain (P < 0.001).ConclusionOur findings emphasize the important role of depression/anxiety symptoms and cognitive impairment in the QoL of patients with chronic schizophrenia. Activating SGAs and employment may improve the QoL of these individuals.Trial registrationThis protocol was registered at chictr.org.cn (Identifier: ChiCTR2100043537).

Pharmacological Mechanism of Herbal Interventions for Bipolar Disorder

: Bipolar disorder is a neuropsychiatric disease characterized by an abundance of undesired ideas and thoughts associated with recurrent episodes of mania or hypomania and depression. Alterations in the circuits, including the prefrontal cortex, striatum, and limbic system, regulate mood and cause variation in several crucial neurotransmitters, including serotonin, dopamine, GABA, and glutamate. Imbalances in dopamine levels have been implicated in the manic phase, while variance in serotonin is linked to depressive episodes. The precise pathophysiology of bipolar disorder is still unknown. Though different treatments are available, like lithium, risperidone, valproic acid, etc., which are widely used, they come with certain limitations, including narrow therapeutic index, hypothyroidism, weight gain, extrapyramidal symptoms, etc. The interest in herbal- based treatments for bipolar disorder arises from the desire for alternative, potentially more natural, and holistic approaches with fewer side effects. The current review focuses on the potential effects of herbal drugs and their derivatives to alleviate the symptoms of bipolar disorder.

Factors Affecting Length of Stay of Patients in a General Psychiatric Hospital in Bahrain: A Retrospective Study.

Length of stay (LOS) in a psychiatric facility can be used as a measurement of the quality of healthcare. Prolonged stays impact the quality of life of psychiatric patients as well as have a huge burden on healthcare expenditures. A retrospective study targeting 153 patients admitted to a general adult ward in a psychiatric hospital in Bahrain, withthe final diagnosis based on ICD-10 criteria. The collected data was analyzed using IBM SPSS Statistics for Windows, Version 26 (IBM Corp.,Armonk, NY). The median LOS was 22 days. LOS among schizophrenia and schizoaffective disorder as well as bipolar affective disorder was significantly longer than other groups. There was no significant difference among groups in terms of gender, age, marital status, social class, and alcohol or substance abuse. The presence of extrapyramidal side effects, history of electroconvulsive therapy (ECT) and the use of restraints during admission were associated with longer LOS. A higher number of previous admissions and number of current medications given during admission in the psychiatric hospital predicted a longer stay in the hospital. Future studies should focus on the effect of better treatment options as well as occupational rehabilitation in ensuring better outcomes for inpatients as well as shorter stays in a psychiatric hospital.

A Review on Therapeutic Strategies against Parkinson's Disease: Current Trends and Future Perspectives.

Parkinson's Disease (PD) is the most common neurodegenerative disorder after Alzheimer's Disease and is clinically expressed by movement disorders, such as tremor, bradykinesia, and rigidity. It occurs mainly in the extrapyramidal system of the brain and is characterized by dopaminergic neuron degeneration. L-DOPA, dopaminergic agonists, anticholinergic drugs, and MAO-B inhibitors are currently used as therapeutic agents against PD, however, they have only symptomatic efficacy, mainly due to the complex pathophysiology of the disease. This review summarizes the main aspects of PD pathology, as well as, discusses the most important biochemical dysfunctions during PD, and presents novel multi-targeting compounds, which have been tested for their activity against various targets related to PD. This review selects various research articles from main databases concerning multi-targeting compounds against PD. Molecules targeting more than one biochemical pathway involved in PD, expected to be more effective than the current treatment options, are discussed. A great number of research groups have designed novel compounds following the multi-targeting drug approach. They include structures combining antioxidant, antiinflammatory, and metal-chelating properties. These compounds could be proven useful for effective multi-targeted PD treatment. Multi-targeting drugs could be a useful tool for the design of effective antiparkinson agents. Their efficacy towards various targets implicated in PD could be the key to the radical treatment of this neurodegenerative disorder.

Zuclopenthixol decanoate toxicity in an 8‐month‐old colt causing extrapyramidal neurological signs

SummaryZuclopenthixol decanoate is a dopamine antagonist licensed for human use to manage schizophrenia and paranoid psychosis. It is in the same drug class (thioxanthene) as fluphenazine decanoate, a drug whose use in horses is reported anecdotally for providing long‐acting sedation. This case study describes severe extrapyramidal signs seen in a Thoroughbred colt after zuclopenthixol decanoate administration. The colt was presented to a referral hospital for an unusual manifestation of colic signs. On admission, the colt began to show clear extrapyramidal neurological signs. The initial suspicion was of fluphenazine decanoate toxicity, which in the limited published literature is treated with intravenous formulations of diphenhydramine hydrochloride and benztropine mesylate. At the time of writing both were unavailable in the United Kingdom without an import license. The closest alternative option, oral diphenhydramine was administered alongside intravenous atropine and pergolide. Improvements in the colt's demeanour and neurological status was noted within 24 h. The colt was hospitalised for a total of 26 days and at time of discharge was clinically normal. Follow‐up communication 3 months after discharge confirmed that the colt had remained neurologically normal. Crucially, toxicology testing submitted to Cornell University was negative for common toxins, including fluphenazine decanoate. Specific secondary testing was performed after suspicion the administration of zuclopenthixol decanoate was raised, which was positive for this compound. Routine drug testing would, therefore, not identify the use of this behaviour modifying drug. Clinical data regarding the use of zuclopenthixol in animals is limited to its use in the translocation of wildlife to relieve stress and aid acclimatisation. To our knowledge, there is no available literature describing the administration of zuclopenthixol decanoate in equine patients.

A Pharmacovigilance Study on Clozapine in the Food and Drug Administration Adverse Event Reporting System: A Regional Comparative Analysis.

This pharmacovigilance study evaluated the profile of clozapine-related adverse events by region using the Food and Drug Administration Adverse Event Reporting System (FAERS). We categorized each case into five regions (America, Europe/West Asia, Oceania, Asia, and Africa) based on the reporting country information in the FAERS database. The number of clozapine-related adverse events reported in each region was aggregated according to the preferred term (PT) and the Standardized Medical Dictionary for Regulatory Activities (MedDRA) Query (SMQ). A total of 101,872 clozapine-related adverse events were registered in the FAERS database. In America and Europe, leukocyte or neutrophil count abnormalities accounted for half of the top 10 PTs by relative reporting rate. However, Asia had higher relative reporting rates of pyrexia and salivary hypersecretion (13.91% and 10.85%, respectively). Regarding the SMQ, the relative reporting rates of infective pneumonia, convulsions, extrapyramidal syndrome, gastrointestinal obstruction, and hyperglycaemia/new onset diabetes mellitus were higher in Asia than in other regions (5.26%, 9.72%, 12.65%, 5.13%, and 8.26%, respectively), with significant differences even after adjusting for confounding factors using multivariate logistic regression analysis. Spontaneous reports of adverse events associated with clozapine show regional disparities, particularly in Asia, where concentration-dependent adverse events are more frequently reported. However, the spontaneous reporting system has several limitations, requiring further research for validation.

Neuroleptic malignant syndrome in puerperal women

Introduction Neuroleptic malignant syndrome is an rare event, even more so among patient from puerperal period. The incidence risk is of 0.11%. It is often occurs when a patient is prescribed on antipsychotic for long duration of time. Case Report We report a case of a female patient, two weeks in post natal period presented with altered behaviour at home. She has prior admission being treated for post partum psychosis with anti psychotic. However antipschotic was withheld as she developed extrapyramidal symptoms while in ward. At home, she developed fever, altered sensorium and fitting-like-episode. On arrival patient was unresponsive and with features of impaired airway patency. Her had unstable vital sign with elevated blood pressure, heart rate and temperature. Brain imagine came back normal, excluding brain pathology. She was diagnosed as neuroleptic malignant syndrome as fulfilled features of elevated creatine kinase. She was treated symptomatic by providing first aid to reduce temperature and started on benzodiazepines. She was subsequently admitted to intensive ward and responded well to treatment Conclusion Physician must be familiar and have high index of suspicious to identify and treat neuroleptic malignant syndrome. Without prompt treatment, it is highly fatal.

Clinical presentations and diagnostic application of proposed biomarkers in psychiatric-onset prodromal dementia with Lewy bodies.

Research criteria for the diagnosis of prodromal dementia with Lewy bodies (DLB) include three clinical subtypes: mild cognitive impairment with Lewy bodies (MCI-LB), delirium-onset prodromal DLB, and psychiatric-onset prodromal DLB. Late-onset psychiatric manifestations are at a higher risk of developing dementia, but its relation to prodromal DLB remains unclear. In addition to the risk of severe antipsychotic hypersensitivity reactions, accurate discrimination from non-DLB cases is important due to the potential differences in management and prognosis. This article aims to review a rapidly evolving psychiatric topic and outline clinical pictures of psychiatric-onset prodromal DLB, including the proposed biomarker findings of MCI-LB: polysomnography-confirmed rapid eye movement sleep behaviour disorder, cardiac [123I]metaiodobenzylguanidine scintigraphy, and striatal dopamine transporter imaging. We first reviewed clinical pictures of patients with autopsy-confirmed DLB. Regarding clinical reports, we focused on the patients who predominantly presented with psychiatric manifestations and subsequently developed DLB. Thereafter, we reviewed clinical studies regarding the diagnostic applications of the proposed biomarkers to patients with late-onset psychiatric disorders. Clinical presentations were mainly late-onset depression and psychosis; however, other clinical manifestations were also reported. Psychotropic medications before a DLB diagnosis may cause extrapyramidal signs, and potentially influences the proposed biomarker findings. These risks complicate clinical manifestation interpretation during the management of psychiatric symptoms. Longitudinal follow-up studies with standardised evaluations until conversion to DLB are needed to investigate the temporal trajectories of core features and proposed biomarker findings. In patients with late-onset psychiatric disorders, identification of patients with psychiatric-onset prodromal DLB provides the opportunity to better understanding the distinct prognostic subgroup that is at great risk of incident dementia. Advances in the establishment of direct biomarkers for the detection of pathological α-synuclein may encourage reorganising the phenotypic variability of prodromal DLB.

Mitochondrial membrane protein-associated neurodegeneration presenting with pure motor neuropathy: A rare case report and review of the literature

Abstract Neurodegeneration with brain iron accumulation is a collective term for neurodegenerative disorders characterized by excessive deposition of iron in the brain, especially in the globus pallidus and substantia nigra. Mitochondrial membrane protein-associated neurodegeneration mainly affects the pyramidal and extrapyramidal systems, and patients can present with various manifestations during disease progression, including gait disorder, dystonia, ataxia, swallowing dysfunction, neuropsychiatric abnormalities, cognitive disabilities, optic atrophy, and, sometimes, peripheral neuropathy. We report a patient of mitochondrial membrane protein-associated neurodegeneration with peripheral neuropathy as the predominant symptom.

A Case of Overlapping Extrapyramidal Side Effects and Neuroleptic Malignant Syndrome

A Case of Overlapping Extrapyramidal Side Effects and Neuroleptic Malignant Syndrome

Cariprazine-Induced Extrapyramidal Symptoms and a Rare Downward Eye Deviation in Oculogyric Crisis: A Case Series

Cariprazine is one of the newer generation antipsychotics with dopamine receptor partial agonist activity which has been approved for management of schizophrenia and bipolar affective disorder. It is known to have lesser propensity to cause extrapyramidal adverse effects due to D2 and D3 partial agonism. We intend to disseminate our newly acquired experience regarding tolerability and the adverse effect profile of cariprazine. In this case series, we describe three cases with different symptom profiles who had experienced significant adverse drug reaction with cariprazine. We also describe a unique presentation of oculogyric crisis in the form of downward fixation of eyes as well the use of amantadine as an alternative option for the management of extrapyramidal adverse effects.

A 12-month longitudinal naturalistic follow-up of cariprazine in schizophrenia.

Cariprazine, a third-generation antipsychotic (TGAs), has demonstrated efficacy in the treatment of schizophrenia with good tolerability profile. Actual real-world literature data are lacking, particularly when exploring its efficacy in the long term. The present study examined the effects of cariprazine treatment on specific psychopathological domains with a particular focus on outcomes and side effects in real-life experience, after a long-term treatment. The present 12-month longitudinal naturalistic study included a sample of subjects with a DSM-5-TR diagnosis of schizophrenia, recruited in the outpatients' psychiatric services of university and community hospitals in Italy, naturally treated with cariprazine. The assessments included: a sociodemographic data sheet, the Structured Clinical Interview for the DSM-5 (SCID-5), the Positive and Negative Symptom Scale (PANSS) and the St. Hans Rating Scale (SHRS). The PANSS was also administered after 6 (T1) and 12 (T2) months of treatment with cariprazine while the SHRS at T1. The total sample consisted of 31 patients, 15 males and 16 females. A significant decrease of the PANSS' subscales, Marder factors and total mean scores emerged at both T1 and T2 with respect to T0. Extrapyramidal symptoms occurred in a minority of patients and in mild or mild/moderate forms: no patient showed moderate forms of psychic/motor akathisia or dystonia, three subjects showed moderate parkinsonism. This study confirms a good efficacy profile of cariprazine in both positive and negative symptoms in patients with Schizophrenia, combined with a good tolerability profile in extrapyramidal symptoms.

Long acting paliperidone injection in patient with bipolar affective disorder, current episode manic with psychotic symptoms

Bipolar Disorder is a chronic mental illness characterized by periods of mania, depression, and mixed episodes that often need lifelong medication. The first line of pharmacotherapy includes lithium, valproate, or second-generation antipsychotics. Paliperidone is a medication that works in the brain and is also known as a second-generation antipsychotic. Paliperidone is available as an oral extended-release tablet and a once-monthly extended-release suspension for intramuscular injection. Long-acting injectables (LAIs) are used to reduce the non-adherence of oral medication. Paliperidone is one of the LAI that could be used to treat manic, hypomanic, and mixed episodes in patients with bipolar disorder. Paliperidone LAI reduces the number of relapses, hospitalization, and length of stay. As reported in this case, a patient with a manic episode who received paliperidone LAI showed favourable results after a week-long observation with no signs of extrapyramidal symptoms.

Afágia ako symptóm Fahrovho syndrómu – kazuistika

Sunmary Aphagia, as a common clinical symptom, demands thorough differential diagnosis with multidisciplinary collaboration. To gradually rule out the common causes of aphagia, the patient must undergo endoscopic and imaging examinations. A crucial modality is a CT scan of the cervical region, where even rarer diagnoses such as Fahr‘s syndrome can be revealed. Fahr‘s syndrome is a rare genetic disorder characterized by the presence of calcified deposits in the basal ganglia. The exact etiology is not yet known, with a presumed multifactorial influence of environmental factors and genetic mutations. It primarily manifests with extrapyramidal symptoms or dementia, and at times, it may exhibit atypical presentations, as seen in our case study. Key words basal ganglia – dysphagia – Fahr’s syndrome

Unveiling Haloperidol's Impact: A Case Report on Induced Parkinsonism and Extrapyramidal Symptoms

Unveiling Haloperidol's Impact: A Case Report on Induced Parkinsonism and Extrapyramidal Symptoms