Search

(R,S)-Ketamine (ketamine) is a dissociative anesthetic that also possesses analgesic and antidepressant activity. Undesirable dissociative side effects and misuse potential limit expanded use of ketamine in several mental health disorders despite promising clinical activity and intensifying medical need. (2R,6R)-Hydroxynorketamine (RR-HNK) is a metabolite of ketamine that lacks anesthetic and dissociative activity but maintains antidepressant and analgesic activity in multiple preclinical models. To enable future assessments in selected human indications, we report the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of RR-HNK in a Phase 1 study in healthy volunteers (NCT04711005). A six-level single-ascending dose (SAD) (0.1-4 mg/kg) and a two-level multiple ascending dose (MAD) (1 and 2 mg/kg) study was performed using a 40-minute IV administration emulating the common practice for ketamine administration for depression. Safety assessments showed RR-HNK possessed a minimal adverse event profile and no serious adverse events at all doses examined. Evaluations of dissociation and sedation demonstrated that RR-HNK did not possess anesthetic or dissociative characteristics in the doses examined. RR-HNK PK parameters were measured in both the SAD and MAD studies and exhibited dose-proportional increases in exposure. Quantitative electroencephalography (EEG) measurements collected as a PD parameter based on preclinical findings and ketamine's established effect on gamma-power oscillations demonstrated increases of gamma power in some participants at the lower/mid-range doses examined. Cerebrospinal fluid examination confirmed RR-HNK exposure within the central nervous system (CNS). Collectively, these data demonstrate RR-HNK is well tolerated with an acceptable PK profile and promising PD outcomes to support the progression into Phase 2., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Hepatoblastoma (HBL) stands as the primary liver tumor most frequently encountered in children, typically identified within the initial 5 years of life. Cases involving patients older than 5 years are very rare. We report the case of a 4-year-old male child who presented to the emergency department with acute onset abdominal pain and fever. Clinical examination revealed significant abdominal distension, correlated with an abdominal mass later confirmed., (© 2024 Published by Elsevier Inc. on behalf of University of Washington.)

Lymphangiomas are rare benign neoplasms traditionally thought to result from congenital lymphatic channel malformations, though they may also be associated with other conditions. Retroperitoneal lymphangiomas account for 1% of all lymphangiomas, and fewer than 200 cases have been reported. A 42-year-old woman was admitted with symptoms of abdominal pain and distension. A computerized tomography (CT) scan showed an abdomino-pelvic mass and a giant uterine myoma. The patient underwent explorative laparotomy and the whole cyst mass was removed along with the uterine myoma. Cystic lymphangiomas are often misdiagnosed because of the vague symptoms and the absence of obvious etiology. A provisional diagnosis can be made with CT but histological examination confirms the diagnosis. Cystic lymphangioma should be included in the differential diagnosis of an ovarian cystic mass. Complete resection can be curative., (© 2024 The Authors. Published by Elsevier B.V.)

Craniocervical junction infections are considered a rare condition and can be associated with degradation of the odontoid ligaments and, the risk of a subsequent atlantoaxial subluxation or dislocation. Osteomyelitis at this level is often seen in immunocompromised patients with, intravenous drug use or infective endocarditis. Atlantoaxial subluxation associated with pharyngeal infection or its surrounding tissues is called Grisel's syndrome. We report the case of a 29-year-old man diagnosed with infectious cervico-occipital osteoarthritis complicated by atlantoaxial dislocation, abscesses located in the retropharyngeal space, and the prevertebral space as well as upper cervical epiduritis. Our purpose is to highlight the role of radiologists in diagnosing this rare yet deadly condition., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Tuberous sclerosis complex is a multisystem genetic disease with autosomal dominant inheritance, characterized by the development of benign tumors known as hamartomas that affect multiple organs. It is a condition with a wide phenotypic spectrum, and its clinical presentation varies over time within the same individual. Hence, the importance of early screening and rigorous monitoring of evolving clinical manifestations. Diagnosis can occur at any age. These tumors are generally benign, but their size and location can have a significant impact on the prognosis and, in some cases, even on life expectancy. Cardiac, neurological, and cutaneous manifestations are most common in childhood. The onset of early and severe epilepsy within the first year of life is associated with neurodevelopmental disorders that impact the quality of life for affected individuals and their families. We present a case of a 22-year-old female patient experiencing inaugural epileptic seizures in adulthood, with magnetic resonance imaging revealing subependymal hamartomas, cortical tubers and radial migration bands accompanied by polycystic kidney disease; the diagnosis of tuberous sclerosis complex was established based on the association of these lesions, which constitute major and minor criteria., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

FLAMES, or fluid-attenuated inversion recovery-hyperintense lesions in anti-myelin oligodendrocyte glycoprotein (anti-myelin oligodendrocyte glycoprotein)-associated encephalitis with seizures, represents a rarely documented syndrome characterized by ambiguous features. Positioned within the spectrum of inflammatory demyelinating diseases of the central nervous system, it is regarded as a distinct subset of myelin oligodendrocyte glycoprotein antibody-associated disease, the latest classification in this domain. Myelin oligodendrocyte glycoprotein antibody-associated disease exhibits a diverse clinical spectrum, spanning from solitary optic neuritis or myelitis to multifocal central nervous system demyelination, manifesting as acute disseminated encephalomyelitis, or cortical encephalitis accompanied by seizures, delineating the fluid-attenuated inversion recovery-hyperintense lesions in anti-myelin oligodendrocyte glycoprotein-associated encephalitis with seizures syndrome. We present a compelling case study of a 30-year-old individual with a history of recurrent seizures initially diagnosed with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. However, the disease's progression more closely resembled self-resolving cerebral cortical encephalitis linked with myelin oligodendrocyte glycoprotein antibodies. In addition, we undertake a systematic review of literature cases to explore the diagnostic significance of magnetic resonance angiography, fluid-attenuated inversion recovery, and specialized markers such as diffusion-weighted imaging and perfusion in discerning fluid-attenuated inversion recovery-hyperintense lesions in anti-myelin oligodendrocyte glycoprotein-associated encephalitis with seizures syndrome and elucidating its distinctive characteristics., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)