Phenotypic spectrum and tumor risk in Simpson-Golabi-Behmel syndrome: Case series and comprehensive literature review.

Simpson-Golabi-Behmel syndrome (SGBS) is a rare congenital overgrowth condition characterized by macrosomia, macroglossia, coarse facial features, and development delays. It is caused by pathogenic variants in the GPC3 gene on chromosome Xq26.2. Here, we performed a comprehensive literature review and phenotyping of known patients with molecularly confirmed SGBS and reviewed a novel cohort of 22 patients. Using these data, we characterized the tumor risk for Wilms tumor and hepatoblastoma to suggest appropriate screening for this patient population. In addition, we discuss the phenotypic overlap between SGBS and Beckwith-Wiedemann Spectrum.

Positron emission tomography neuroimaging of [18F]fluorodeoxyglucose uptake and related behavior in the Pink1-/- rat model of Parkinson disease.

Introduction: Parkinson disease (PD) is a neurodegenerative condition affecting multiple sensorimotor and cognitive systems. The Pink1-/- rat model exhibits vocal, cognitive, and limb use deficits seen in idiopathic PD. We sought to measure glucose metabolism in brain regions in Pink1-/- and wild type (WT) rats, and to associate these to measures of ultrasonic vocalization, cognition, and limb use behavior. Methods: Pink1-/- (n = 12) and WT (n = 14) rats were imaged by [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) in a repeated measures design at approximately 10 months of age and 6 weeks later. Relative regional glucose metabolism was indexed by whole brain normalized FDG uptake, which was calculated for 18 regions identified a priori for comparison. Behavioral measures included tests of communication via ultrasonic vocalization, cognition with 5-Choice Serial Reaction Time Test (5-CSRTT), and limb use with Cylinder Test and Challenge Beam. Results: Relative glucose metabolism was significantly different in Pink1-/- rats in prelimbic area, striatum, nucleus ambiguus, globus pallidus, and posterior parietal association cortex compared to WT controls. For behavioral measures, Pink1-/- rats demonstrated quieter vocalizations with a restricted frequency range, and they showed increased number of foot-faults and hindlimb steps (shuffling) in limb motor tests. Significant behavior vs. brain correlations included associations of ultrasonic vocalization parameters with glucose metabolism indices in locus coeruleus and substantia nigra. Conclusion: FDG PET reveals abnormalities in relative regional brain glucose metabolism in Pink1-/- rats in brain regions that are important to cognition, vocalization, and limb motor control that are also impacted by Parkinson disease. This method may be useful for mechanistic studies of behavioral deficits and therapeutic interventions in translational studies in the Pink1-/- PD model.

Primary midbrain germinomas: Report of a rare case with an updated review of the literature.

Intracranial germinomas are most commonly extra-axial germ cell tumors that are predominantly found in the pineal and suprasellar regions. Primary intra-axial midbrain germinomas are extremely rare, with only eight reported cases. Here we present a 30-year-old man who presented with severe neurological deficits, with an MRI that showed a heterogeneously enhancing mass with ill-defined margins in the midbrain, and with surrounding vasogenic edema extending to the thalamus. The presumptive preoperative differential diagnosis included glial tumors and lymphoma. The patient underwent a right paramedian suboccipital craniotomy and biopsy obtained through the supracerebellar infratentorial transcollicular approach. The histopathological diagnosis was reported as pure germinoma. After patient discharge, he received chemotherapy with carboplatin and etoposide, followed by radiotherapy. Follow-up MRI at up to 26 months showed no contrast-enhancing lesions but a mild T2 FLAIR hyperintensity adjacent to the resection cavity. Differential diagnosis of midbrain lesions can be challenging and should include glial tumors, primary central nervous system lymphoma, germ cell tumors, and metastasis. Accurate diagnosis requires adequate tissue sampling. In this report, we present a very rare case of a primary intra-axial germinoma of the midbrain which is biopsied via a transcollicular approach. This report is also unique as it provides the first surgical video of an open biopsy and the microscopic appearance of an intra-axial primary midbrain germinoma via a transcollicular approach.

Dysphagia in Parkinson Disease: Part II-Current Treatment Options and Insights from Animal Research.

Purpose of Review: Dysphagia is highly prevalent in Parkinson disease (PD) but is not typically identified nor treated until later in the disease process. This review summarizes current pharmacological, surgical, and behavioral treatments for PD-associated dysphagia and contributions from translational animal research. Recent Findings: Swallowing is a complex physiologic process controlled by multiple brain regions and neurotransmitter systems. As such, interventions that target nigrostriatal dopamine dysfunction have limited or detrimental effects on swallowing outcomes. Behavioral interventions can help target PD-associated dysphagia in mid-to-late stages. Animal research is necessary to refine treatments and useful in studying prodromal dysphagia. Summary: Dysphagia is an early, common, and debilitating sign of PD. Current pharmacological and surgical interventions are not effective in ameliorating swallowing dysfunction; behavioral intervention remains the most effective approach for dysphagia treatment. Animal research has advanced our understanding of mechanisms underlying PD and PD-associated dysphagia, and continues to show translational promise for the study of dysphagia treatment options.

Assays of tongue force, timing, and dynamics in rat and mouse models.

Communication and swallowing are highly complex sensorimotor events that are tightly linked to respiration and vital to health and well-being. The tongue is a complex organ, often described as a muscular hydrostat, that is crucial for maintaining airway patency, preparing and safely transporting food/liquid, and rapidly changing position and shape for speech. As with any complex behavior, tongue function can be compromised with aging, diseases/conditions, trauma, or as a pharmacologic side effect. As such, modeling lingual function and dysfunction for basic and translational research is paramount; understanding how the nervous system controls tongue function for complex behavior is foundational to this work. Non-invasive access to tongue tissues and kinematics during awake behavior has been historically challenging, creating a critical need to measure tongue function in model systems. Germane to this field of study are the instruments and assays of licking/lapping and drinking, including tongue force and timing measures, many of which were designed or modified by Dr. Stephen C. Fowler. The focus of this paper is to review some of the important contributions of measuring tongue behaviors in awake rats and mice and how these have been modified by other researchers to advance translational science.