BackgroundNeurological presentations of pediatric intussusception lead to delayed diagnosis, higher rates of surgical intervention, and worse outcomes compared with classic presentations. These atypical manifestations, including lethargy, altered mental status, and rarely movement disorders, may predominate and redirect evaluation toward primary neurological etiologies, delaying recognition of this reversible surgical emergency.Case PresentationA previously healthy 2-year-old boy presented with clustered orofacial dyskinesias and irregular upper-extremity jerks without exposure to dopamine-receptor antagonists. He was initially misdiagnosed with tardive dyskinesia and treated with biperiden without improvement. Neurologic examination and brain magnetic resonance imaging were normal. During observation, he developed bilious vomiting. Abdominal imaging revealed ileocolic intussusception. Pneumatic reduction was unsuccessful, and surgical exploration demonstrated an invaginated Meckel diverticulum with ischemic bowel requiring resection. Abnormal movements resolved completely following surgery.MethodsWe conducted a systematic case-based review of published pediatric cases of intussusception presenting with neurological manifestations.ResultsNeurological symptoms-most commonly lethargy and altered mental status-frequently dominated the initial presentation and contributed to significant diagnostic delay (median 12 hours vs 5 hours in classic presentations, P < 0.001). Critically, patients with neurological presentations required surgical intervention in 60% of cases compared with 18% of classic presentations (P < 0.001), with approximately one-quarter of surgical patients requiring bowel resection, reflecting more advanced disease at diagnosis.ConclusionIntussusception should be considered in infants and young children with unexplained acute neurological symptoms, particularly when initial neurologic evaluation is unrevealing. Early abdominal imaging may prevent diagnostic delay in this reversible surgical emergency.

Parkinson's disease (PD) has been associated with some types of food and drugs. Here, we query PubMed for the association of PD with foods and drugs, using a list of 217,776 compounds derived from the Human Metabolome Database (HMDB). To calculate associations, a Python script was developed to query PubMed for co-citations of PD with each compound, and adjust this count for compound abundance. Notably, PD is found to be associated with small-molecule drugs, adjunctive therapies, contraindicated drugs, diagnostic agents, biomarkers, conditional essential molecules, and inducers. Drugs include L-dopa (49%), carbidopa (63%), benserazide (50%), entacapone (74%), tolcapone (56%), rasagiline (76%), selegiline (46%), pargyline (4%), ropinirole (61%), pramipexole (56%), lisuride (27%), cabergoline (16%), bromocriptine (12%), and zonisamide (9%). Adjunctive therapies include droxidopa (33%), trihexyphenidyl (28%), biperiden (17%), amantadine (24%), memantine (7%), rivastigmine (13%), donepezil (6%), galantamine (4%), domperidone (6%), clonazepam (4%), tetrabenazine (16%), mazindol (13%), quetiapine (6%), and clozapine (4%). Contraindicated drugs include haloperidol (4%), sulpiride (3%), and methyldopa (6%). Diagnostic agents include FP-CIT (60%) and beta-CIT (43%). Biomarkers include 3-methoxytyrosine (48%) and homovanillic acid (12%). Endogenous cofactors include tetrahydrobiopterin (4%) and Coenzyme Q10 (4%). Chemical inducers of PD include 6-hydroxydopamine (40%), N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 78%), tetrahydropyridine (77%), probenecid (4%), quinolinic acid (4%), 1,2,3,4-tetrahydroisoquinoline (TIQ, 16%), salsolinol (32%), rotenone (25%), and β-Methylamino-L-alanine (BMAA, 29%). Notably, our study highlights conditional essential endogenous cofactors associated with PD and emphasizes rational directions for investigation in PD.

Traumatic brain injury (TBI) disrupts brain function and may lead to post-traumatic epilepsy (PTE), a long-term complication. Anticholinergic drugs, such as biperiden, have shown potential in modulating neural plasticity. This study evaluated whether biperiden treatment influences motor and cognitive recovery, seizure susceptibility, and neurovascular and inflammatory responses in rats subjected to the lateral fluid percussion injury (LFPI) model. Adult male Wistar rats underwent LFPI or sham surgery and were treated with saline or biperiden (8 mg/kg) administered intraperitoneally every 8 h for 10 days, starting 6 h after trauma. Neuromotor battery tests were assessed over 28 days, spatial memory at 30 days using the Barnes Maze, and seizure susceptibility was tested with pentylenetetrazol (PTZ) at 90 days after trauma as a second hit. Plasma samples were collected 10 days after trauma for Single Molecular Array (SIMOA) analysis of trauma biomarkers, neurofilament light chain (NfL), and total tau. Histological and immunofluorescence analyses were conducted at 91 days. TBI significantly increased plasma NfL levels compared to the Naive group, indicating neuronal damage. Animals that underwent LFPI and were treated with saline solution were called TBI-SAL group, while animals that underwent LFPI and were treated with biperiden solution were called TBI-BIP group. TBI-SAL group exhibited memory impairments and random search strategies in the Barnes Maze. Both TBI groups (those treated with saline and with biperiden) exhibited higher seizure susceptibility to PTZ at 30 mg/kg, but biperiden slightly reduced seizure intensity. Histological analyses revealed larger lesion volumes, reduced NeuN expression in hippocampal regions (CA1, CA3), and altered astrocytic and microglial morphology in the TBI-SAL group. Notably, biperiden treatment promoted vascular remodeling, characterized by an increase in vessel density, in the motor cortex and hippocampal regions, suggesting potential modulation of post-traumatic neuroinflammation. Biperiden enhanced vascular remodeling and partially mitigated long-term histopathological changes after TBI, though its protective effects on cognitive and seizure-susceptibility responses were limited. These findings highlight biperiden's potential to influence vascular and inflammatory responses in the injured brain.

Traumatic brain injury (TBI) remains a leading cause of morbidity and mortality, with no effective treatments available. Biperiden, a muscarinic receptor antagonist, has demonstrated beneficial effects by modulating neural plasticity and reducing excitotoxicity. This study investigated the acute impact of cellular and structural changes in a moderate TBI model using lateral fluid percussion injury (LFPI) in male Wistar rats. Biperiden (8 mg/kg) was administered intraperitoneally at 6 h post-injury, followed by two additional doses at 8-hour intervals. Brain and blood were collected twenty-four hours after TBI for, histological, immunohistochemical, and Single Molecule Array (SIMOA) analyses. Results revealed that biperiden-treated (TBI-BIP) rats exhibited diminished degenerating neurons, lower T-tau and NfL levels, decreased astrocyte activation, and restored microglia morphology compared to saline-treated (TBI-SAL) rats, attenuating TBI-induced damage. Motor deficits were most pronounced on Day 1 post-trauma, with non-significant statistical difference in neuroscore performance between the TBI groups, however the biperiden treatment modulates astrocyte reactivity, diminish gliosis, and promote a neuroprotective phenotype. Additionally, biperiden preserves microglial branching following injury. These findings demonstrate that biperiden exerts beneficial effects during the acute phase of TBI by decreasing neuronal degeneration, excitotoxicity, and inflammation, highlighting its therapeutic potential for post-TBI intervention.

The prevalence of Parkinson disease is increasing globally. Despite the existence of effective and affordable medicines for Parkinson disease, access to these medicines is limited in the World Health Organization (WHO) African Region. Several factors influence accessibility, including lack of prioritization of Parkinson disease, shortage of a trained health workforce, barriers to health financing and lack of inclusion of medicines in national essential medicines lists. We determined alignment of the most recent national essential medicines lists of 47 countries in the WHO African Region with the 23rd edition of the WHO Model list of essential medicines for Parkinson disease medicines. Overall, of any formulation or strength, 81% (38/47) of countries included levodopa + carbidopa or levodopa + benserazide as a therapeutic alternative on their national lists; and 79% (37/47) included biperiden or trihexyphenidyl as a therapeutic alternative. Inclusion of specific formulations for medicines was lower; for example, 45% (21/47) of countries included levodopa + carbidopa or levodopa + benserazide in a 4:1 ratio. Furthermore, 11% (5/47) of national essential medicines lists included none of the four medicines. While inclusion of medicines for Parkinson disease in national essential medicines lists provides no guarantee of immediate access, it can encourage procurement, prescribing and use, and can help lower costs, raise awareness of and create political will for Parkinson disease treatment. This analysis provides further evidence of the need for action to improve the accessibility of medicines for Parkinson disease in the WHO African Region.

Biperiden is no longer marketed in the United States. No information is available on the use of biperiden during breastfeeding. Long-term use of biperiden might reduce milk production or milk letdown, but a single dose is not likely to interfere with breastfeeding. During long-term use, observe for signs of decreased lactation (e.g., insatiety, poor weight gain).

Biperiden (BIP), a muscarinic type 1 (M1) receptor antagonist, has been proposed as a pharmacological model for episodic memory impairment in mild cognitive impairment (MCI) and early stages of Alzheimer's disease (AD). Understanding the effects of BIP on memory could also be relevant for the development of M1 agonists to improve memory. In this study, we specifically examined how BIP affected the serial position effect (SPE) in a word learning task. Since MCI and AD show memory deficits for the first words of a list (primacy effect) we predicted a similar effect for BIP. Data from four previous studies were collated in which the effects of BIP or placebo treatment was tested a double-blind randomized design. For testing the SPE effect, we calculated the average of the first 3 words (primacy), the last 3 words (recency) and the middle 10 words. To control for the level of performance in the different studies, z-scores were calculated. Overall, the analyses revealed a clear SPE effect. BIP did not impair the primacy or recency effect but was found to impair the memory for the middle 10 words in the delayed recall test. These findings indicate that blocking the M1 receptor not does impair the primacy or the recency effect in the SPE. Although BIP treatment has an overall impairing effect on episodic memory, it does not model primacy effect deficits in MCI and AD. However, M1 receptors appear to modulate the memory for weakly encoded/stored information suggesting that M1 agonist could improve verbal episodic memory.

Evidence from the literature suggests that alcohol use disorder (AUD) is closely associated with alterations in neuronal plasticity and the memory system, related to modifications in muscarinic receptors. The present study aimed to investigate the effects of systemic injection of biperiden, a muscarinic cholinergic antagonist, in experimental protocols of progressive ratio, 24-hour binge alcohol consumption, and reinstatement of context-induced ethanol self-administration. The results demonstrated that biperiden at doses of 5 and 10 mg/kg (i.p.) effectively reduced the animals' motivation for alcohol consumption, as evidenced by decreased responses on the active lever and a reduction in the last ratio achieved in the progressive ratio protocol. Furthermore, these same doses significantly reduced ethanol consumption in the 24-hour binge protocol. Treatment with biperiden at doses of 1, 5, and 10 mg/kg also attenuated alcohol-seeking behavior after re-exposure to the context associated with ethanol self-administration. These findings suggest that biperiden may have therapeutic potential in the treatment of alcohol use disorder, indicating that modulation of the cholinergic system could be a promising avenue for further investigation.

We describe the case of a 77-year-old man, who was admitted for the initiation of chemotherapy for stage IV small cell lung cancer without cerebral metastases. On the first day post-admission, the patient developed altered mental status and right-sided weakness after premedication with ondansetron and dexamethasone. Symptoms resolved spontaneously within 90 minutes. An ischemic event was suspected despite unremarkable brain imaging. Prophylactic anticoagulation and statins were initiated. Five days later, a second episode of altered mental status, anisocoria, facial paresis, and severe dysarthria occurred following ondansetron administration. Bloodwork revealed significant hyponatremia (116 mEq/L), suggesting Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH), despite this suspicion, there was no further investigation to confirm this diagnosis due to rapid symptom reversal after biperiden administration, implicating an adverse reaction to ondansetron. Ondansetron and metoclopramide were discontinued, hyponatremia was corrected, and no further episodes occurred during the hospital stay. This case highlights the necessity of awareness for adverse reactions of ondansetron that can mimic cerebrovascular events and the need for a thorough revision of medication in complex cases.

Despite the abundance of large-scale molecular and drug-response data, current research on early-onset Parkinson's disease (EOPD) markers often lacks mechanistic interpretations of drug-gene relationships, limiting our understanding of how drugs exert their therapeutic effects. While existing studies provide valuable EOPD markers, the mechanisms by which targeted drugs act remain poorly understood. We propose DTI-Prox, a novel workflow that identifies potentially overlooked EOPD markers and suggests relevant drug targets. DTI-Prox employs network proximity to measure how closely connected a drug and gene are within a biological network. Additionally, node similarity, which assesses the functional resemblance between network nodes, reveals meaningful drug-gene connections. DTI-Prox identifies 417 novel drug-target pairs and four previously unreported EOPD markers (PTK2B, APOA1, A2M, and BDNF), demonstrating significant pathway enrichment in neurodegenerative processes. Notably, shared pathway analysis shows that prioritized drugs such as Amantadine, Apomorphine, Atropine, Benztropine, Biperiden, Bromocriptine, Cabergoline, Carbidopa, and Citalopram, currently used for other conditions, interact with key EOPD-associated diagnostic markers, suggesting their potential for drug repurposing. The constructed functional network's validity is reinforced by statistically significant drug-target pairs. The findings provide new insights into EOPD drug mechanisms and identify promising therapeutic candidates, potentially leading to more effective, personalized treatment approaches for EOPD patients.

Metoclopramide is a useful antiemetic drug that is widely used in medical emergencies. This drug can cause extrapyramidal side effects that are worrying. An 18-year-old girl student unintentionally consumed a large dose (60 mg) of metoclopramide, exceeding the recommended therapeutic dose, for the management of nausea and vomiting. Approximately six hours after the ingestion of the medication, she developed neck dystonia and upward deviation of the eyes. Seeing these symptoms and worrying about their child's physical condition, the parents took her to the local medical center in northern Iran. With the diagnosis of the extrapyramidal syndrome and intramuscular administration of biperiden 5 mg ampoule twice at 12-h intervals, unfortunately, the symptoms did not improve and finally he was referred to our hospital. Dystonic reactions caused by metoclopramide can be misdiagnosed and it is necessary to be monitored and treated appropriately to reduce the family's concern about its unpleasant side effects.