Imaging Pathway of a Pediatric Patient with Succinate Dehydrogenase B-Deficient Paraganglioma.

Pheochromocytoma and paraganglioma are rare in children, at only 1 in every 50,000 cases. Even though some cases are sporadic, they have been connected to syndromes such as von Hippel-Lindau, multiple endocrine neoplasia types IIa and IIb, neurofibromatosis type 1, and hereditary pheochromocytoma-paraganglioma syndromes. A genetic mutation causes around 60% of pheochromocytomas and paragangliomas in children under 18. Methods: A 15-y-old child with a 6-y history of back discomfort is presented. The justification for using 2 functional imaging modalities, 68Ga-DOTATATE PET/CT and 123I-meta-iodobenzylguanidine SPECT/CT, is examined in this case study. We reviewed the patients' journey since the first referral for imaging. Results: Delaying the molecular imaging modalities has affected patients' overall diagnosis and applied treatment outcomes. Conclusion: This case study investigates the potential for the earlier use of various diagnostic modalities in conjunction with diagnostic testing to facilitate an earlier diagnosis. However, since this study is based solely on imaging and lacks access to the patient's clinical or family history, factors such as potential inequities in health-care facilities, health literacy, and socioeconomic status are not addressed. It is essential to acknowledge these influences as they contribute to the inequitable access to health-care settings in New Zealand.

First in human trial of a type I positive allosteric modulator of alpha7-nicotinic acetylcholine receptors: Pharmacokinetics, safety, and evidence for neurocognitive effect of AVL-3288.

Type I positive allosteric modulators (PAMs) of the alpha7-nicotinic receptor enhance its cholinergic activation while preserving the spatiotemporal features of synaptic transmission and the receptor's characteristic rapid desensitization kinetics. Alpha7-nicotinic receptor agonists have shown promise for improving cognition in schizophrenia, but longer-term trials have been disappointing. Therefore, the type I PAM AVL-3288 was evaluated for safety and preliminary evidence of neurocognitive effect in healthy human subjects. Single-dose oral administration in ascending doses was conducted in a double-blind, placebo-controlled Phase I trial in non-smokers. The trial found indication of positive but non-significant effects on neurocognition at 10 and 30 mg, two doses that produced overlapping peak levels. There was also some evidence for effects on inhibition of the P50 auditory evoked potential to repeated stimuli, a biomarker that responds to alpha7-nicotinic receptor activation. The pharmacokinetic characteristics were consistent between subjects, and there were no safety concerns. The effects and safety profile were also assessed at 3 mg in a cohort of smokers, in whom concurrent nicotine administration did not alter either effects or safety. The trial demonstrates that a type I PAM can be safely administered to humans and that it has potential positive neurocognitive effects in central nervous system (CNS) disorders.