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UNASSIGNED: Childhood gratification syndrome (CGS) refers to self-stimulatory or masturbatory behaviors in children, which may have an onset as early as in infancy (IGS).
UNASSIGNED: The aim of this review is to understand the various clinical manifestations of CGS/IGS and their clinical differentiation from commonly misdiagnosed neurological and physical illnesses and to formulate a preliminary approach to their diagnosis and management.
UNASSIGNED: This narrative review is based on a search of literature over the past 50 years (1972-2022) in three online databases (PubMed/Medline, Embase, and Google Scholar).
UNASSIGNED: The behaviors are episodic, occurring for brief periods, involving posturing, stereotypical limb movements, pubic pressure with autonomic hyperactivity, and postepisodic lethargy. They mimic seizures, movement disorders, abdominal pain, and tics. The paper also highlights the gap in the current knowledge to guide future research in the area. CGS usually represents nonpathological \"pleasure-seeking\" habits of childhood, but at times, it may become problematic for the child and his family. A careful history and videotape analysis of the events confirms the diagnosis and behavioral therapy with parental reassurance as the mainstay of treatment.
UNASSIGNED: A better understanding and clinical awareness of the CGS are necessary to prevent misdiagnosis and delay in appropriate intervention.

NLX-112 (i.e., F13640, befiradol) exhibits nanomolar affinity, exceptional selectivity and full agonist efficacy at serotonin 5-HT1A receptors. NLX-112 shows efficacy in rat, marmoset and macaque models of L-DOPA induced dyskinesia (LID) in Parkinson\'s disease and has shown clinical efficacy in a Phase 2a proof-of-concept study for this indication. Here we investigated, in rats, its pharmacodynamic, pharmacokinetic (PK) and brain 5-HT1A receptor occupancy profiles, and its PK properties in the absence and presence of L-DOPA. Total and free NLX-112 exposure in plasma, CSF and striatal ECF was dose-proportional over the range tested (0.04, 0.16 and 0.63 mg/kg i.p.). NLX-112 exposure increased rapidly (Tmax 0.25-0.5h) and exhibited approximately threefold longer half-life in brain than in plasma (1.1 and 3.6h, respectively). At a pharmacologically relevant dose of 0.16 mg/kg i.p., previously shown to elicit anti-LID activity in parkinsonian rats, brain concentration of NLX-112 was 51-63 ng/g from 0.15 to 1h. In microPET imaging experiments, NLX-112 showed dose-dependent reduction of 18F-F13640 (i.e., 18F-NLX-112) brain 5-HT1A receptor labeling in cingulate cortex and striatum, regions associated with motor control and mood, with almost complete inhibition of labeling at the dose of 0.63 mg/kg i.p.. Co-administration of L-DOPA (6 mg/kg s.c., a dose used to elicit LID in parkinsonian rats) together with NLX-112 (0.16 mg/kg i.p.) did not modify PK parameters in rat plasma and brain of either NLX-112 or L-DOPA. Here, we demonstrate that NLX-112\'s profile is compatible with \'druggable\' parameters for CNS indications, and the results provide measures of brain concentrations and 5-HT1A receptor binding parameters relevant to the anti-dyskinetic activity of the compound.

Critical periods are windows of heightened plasticity occurring during neurodevelopment. Alterations in neural activity during these periods can cause long-lasting changes in the structure, connectivity, and intrinsic excitability of neurons, which may contribute to the pathology of neurodevelopmental disorders. However, endogenous regulators of critical periods remain poorly defined. Here, we study this issue using a fruit fly (Drosophila) model of an early-onset movement disorder caused by BK potassium channel gain of function (BK GOF). Deploying a genetic method to place robust expression of GOF BK channels under spatiotemporal control, we show that adult-stage neuronal expression of GOF BK channels minimally disrupts fly movement. In contrast, limiting neuronal expression of GOF BK channels to a short window during late neurodevelopment profoundly impairs locomotion and limb kinematics in resulting adult flies. During this critical period, BK GOF perturbs synaptic localization of the active zone protein Bruchpilot and reduces excitatory neurotransmission. Conversely, enhancing neural activity specifically during development rescues motor defects in BK GOF flies. Collectively, our results reveal a critical developmental period for limb control in Drosophila that is influenced by BK channels and suggest that BK GOF causes movement disorders by disrupting activity-dependent aspects of synaptic development.

Belly dancer dyskinesia, a rare disease, may often be overlooked as a regular nonspecific abdominal pain, and therefore, high index of clinical suspicion is required to avert misdiagnosis.

Belly dancer\'s dyskinesia (BDD) is characterized by involuntary abdominal wall movements that are rhythmic, repetitive, and dyskinetic. The present study aims to review BDD\'s etiology, pathophysiology, and management. We searched six databases to locate existing reports on BDD published from 1990 to October 2023 in electronic form. A total of 47 articles containing 59 cases were found. The majority of the patients affected by BDD were female, accounting for 61.01% (36/59) of the cases. The mean and median ages were 49.8 (standard deviation: 21.85) and 52 years (range: 7-85), respectively. The BDD was unilateral in only 3.38% (2/59). The most commonly reported causes associated with BDD were 17 idiopathic, 11 drug-induced, 11 postsurgical procedures, 5 pregnancies, and 4 Vitamin B12 deficiencies. BDD is a diagnosis of exclusion, and other more common pathologies with similar presentation should be ruled out initially. Differential diagnostic reasoning should include diaphragmatic myoclonus, cardiac conditions, truncal dystonia, abdominal motor seizures, propriospinal myoclonus, and functional or psychiatric disorders.

Tardive dyskinesia (TD) is a serious and often permanent complication usually seen after the long-term use of antipsychotic medications, and multiple other classes of medications have been reported to cause TD or TD-like syndromes. TD can affect any part of the body, but it most commonly affects the mouth, lips, and tongue. We present a case of oral-buccal-lingual dyskinesia in an 86-year-old female from the long-term use of levetiracetam for a seizure disorder. The patient was started on levetiracetam four years before admission and was noted to have an acute onset of oral-buccal-lingual dyskinesia that was so severe it interrupted the patient\'s speech and feeding. The patient\'s dyskinesias are completely resolved after cross-tapering levetiracetam 500 mg twice a day with valproic acid 750 mg daily. Additionally, there was a global recovery of the patient\'s mood and psychosis after the cross-taper. Our case highlights the potential implications of levetiracetam in dyskinetic movements and neuropsychiatric symptoms, and it warrants close monitoring of patients taking this medication especially elderly with multiple comorbidities and compromised renal function. Moreover, the case suggests the reversible nature of both neuropsychiatric symptoms and dyskinesias.

The striatum integrates dopaminergic and glutamatergic inputs to select preferred versus alternative actions. However, the precise mechanisms underlying this process remain unclear. One way to study action selection is to understand how it breaks down in pathological states. Here, we explored the cellular and synaptic mechanisms of levodopa-induced dyskinesia (LID), a complication of Parkinson\'s disease therapy characterized by involuntary movements. We used an activity-dependent tool (FosTRAP) in conjunction with a mouse model of LID to investigate functionally distinct subsets of striatal direct pathway medium spiny neurons (dMSNs). In vivo, levodopa differentially activates dyskinesia-associated (TRAPed) dMSNs compared to other dMSNs. We found this differential activation of TRAPed dMSNs is likely to be driven by higher dopamine receptor expression, dopamine-dependent excitability, and excitatory input from the motor cortex and thalamus. Together, these findings suggest how the intrinsic and synaptic properties of heterogeneous dMSN subpopulations integrate to support action selection.

In the present study, we explored the development of a novel noninvasive liposomal drug delivery material for use in intranasal drug delivery applications in human diseases. We used drug entrapment into liposomal nanoparticle assembly to efficiently deliver the drugs to the nasal mucosa to be delivered to the brain. The naturally occurring flavonoid 7,8-dihydroxyflavone (7,8-DHF) has previously been shown to have beneficial effects in ameliorating Parkinson\'s disease (PD). We used both naturally occurring 7,8-DHF and the chemically modified form of DHF, the DHF-ME, to be used as a drug candidate for the treatment of PD and l-DOPA induced dyskinesia (LID), which is the debilitating side effect of l-DOPA therapy in PD. The ligand-protein interaction behavior for 7,8-DHF and 6,7-DHF-ME was found to be more effective with molecular docking and molecular stimulation studies of flavonoid compounds with TrkB receptor. Our study showed that 7,8-DHF delivered via intranasal route using a liposomal formulation ameliorated LID in hemiparkinsonian mice model when these mice were chronically administered with l-DOPA, which is the only current medication for relieving the clinical symptoms of PD. The present study also demonstrated that apart from reducing the LID, 7,8-DHF delivery directly to the brain via the intranasal route also corrected some long-term signaling adaptations involving ΔFosB and α Synuclein in the brain of dopamine (DA) depleted animals.