Traumatic brain injury (TBI) is associated with cognitive impairment and neurobiological alterations potentially influenced by cholinergic signaling. Although biperiden has been investigated as a potential antiepileptogenic therapy after TBI, its neuropsychological safety remains poorly understood. To evaluate the longitudinal neuropsychological safety of biperiden following TBI using standardized cognitive assessments and longitudinal analyses. Patients with moderate-to-severe TBI previously enrolled in a randomized controlled trial received biperiden or placebo treatment in the acute post-injury phase. Neuropsychological outcomes were assessed using tests from the Wechsler Adult Intelligence Scale, Five Digit Test, Rey Auditory Verbal Learning Test and Rey-Osterrieth Complex Figure Test. Fifty-four participants (placebo n = 30; biperiden n = 24) were included, with follow-up at 3-9, 10-16, and 20-36 months. Linear mixed-effects models showed no differences in cognitive outcomes between treatment groups. Greater TBI severity was associated with poorer processing speed, working memory, and verbal performance, including vocabulary and delayed recall. Temporal and parietal lesions were associated with reduced language and executive performance and recovery. Higher educational level was associated with better performance across specific domains. Biperiden showed no evidence of detrimental long-term neuropsychological effects following TBI. Cognitive outcomes were primarily determined by injury severity, lesion distribution, and cognitive reserve rather than pharmacological exposure, supporting its tolerability in acute post-TBI interventions targeting neuroplasticity modulation.

Traumatic brain injury (TBI) leads to extensive structural damage, neuronal loss, and functional deficits, along with marked disruption of cholinergic signaling and acute surges in acetylcholine. Biperiden, a muscarinic cholinergic antagonist, has emerged as a potential neuroprotective agent due to its ability to modulate synaptic plasticity and reduce excitotoxicity. Here, we evaluated the acute effects of biperiden in a translational non-human primate model of moderate TBI. Marmosets (Callithrix jacchus,n = 39) subjected to lateral fluid percussion injury (LFPI) received intraperitoneal biperiden (8 mg/kg) beginning 6 h post-injury, followed by two additional doses administered at 8 h intervals. At 24 h post-injury, brain tissue and serum were assessed using histology, immunofluorescence, and Single Molecule Array (SIMOA). Twenty-four hours post-trauma, biperiden treatment reduced hippocampal neuronal degeneration, decreased UCH-L1 levels, and attenuated astrocyte activation compared to saline-treated controls. Although biperiden is a clinically characterized muscarinic antagonist, the direct muscarinic target was not assessed in this primate model. These findings provide preliminary evidence that repeated dosing with biperiden may modulate early neurovascular and glial responses and provide acute neuroprotection following moderate TBI in marmosets, mitigating neuronal injury, excitotoxicity, and inflammation. This work highlights biperiden as a promising therapeutic candidate for early intervention after TBI.

Advanced-stage Parkinson's disease (PD) and myasthenia gravis (MG) share overlapping clinical features, including dysphagia, dysarthria, fatigue, and fluctuating symptoms. When PD precedes MG, these manifestations may be misinterpreted as a progression of PD, potentially leading to an underdiagnosis of MG. Although the coexistence of PD and MG is rare, it nevertheless requires careful consideration. Furthermore, the pharmacological treatments for these two disorders differ substantially, and medications used for one condition may exacerbate the other condition. We report a patient with PD complicated by MG, in whom anticholinergic treatment with biperiden led to the exacerbation of MG-related symptoms, ultimately resulting in the diagnosis of MG.

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).