Neuropsychiatric Symptoms of Moyamoya Disease: Considerations for the Clinician.

Neurocognitive impairment in moyamoya disease is common, under recognized, and potentially devastating. The purpose of this paper is to provide an updated overview on this topic for the practicing clinician. We searched PubMed for keywords including cognitive impairment, neurocognitive dysfunction, and neuropsychological recovery in moyamoya disease. We summarized the literature to provide a concise review of the treatment and management of neuropsychiatric symptoms associated with moyamoya disease. Neuropsychiatric sequelae have conventionally been attributed to chronic cerebral hypoperfusion and/or stroke. Cognitive dysfunction in adults with moyamoya disease is most commonly in the form of impaired executive function, whereas intelligence is the predominant impairment in children with moyamoya disease. Pharmacotherapy for treatment of the neuropsychiatric symptoms associated with moyamoya disease is appropriate and can improve quality of life; however, careful consideration is needed to avoid adverse cerebrovascular events. It remains unclear as to whether surgical revascularization improves or stabilizes cognitive performance and outcomes. Additional prospective studies are warranted to better understand the long-term impact of revascularization on cognitive functioning in moyamoya disease.

Presyncope and Ophthalmoparesis Due to Intracranial Erdheim-Chester Disease.

Introduction: An 82-year-old female presented to the emergency department with presyncope and was found to be bradycardic with proptosis and ophthalmoparesis. MRI revealed an extra-axial enhancing mass compressing the medulla and bilateral enhancing retro-orbital masses. Case Description: Imaging, including nuclear medicine bone scan, PET CT, and cardiac MRI raised the suspicion for a histiocytic neoplasm. These findings, along with a fibrohistiocytic infiltrate on bone biopsy and a BRAF V600E oncogenic mutation on plasma cell-free DNA confirmed a diagnosis of Erdheim-Chester disease. Discussion: These enhancing masses invoke a broad differential, including a histiocytic or granulomatous process, fungal infection, amyloidosis, IgG4 disease, and lymphoma. Systematic laboratory, radiologic, pathology, and genetic testing yielded a diagnosis of this rare histiocytic disorder with frequent neurologic involvement.

Trimethylamine-N-oxide acutely increases cardiac muscle contractility.

Cardiovascular disease is a major cause of morbidity and mortality among patients with chronic kidney disease (CKD). Trimethylamine-N-oxide (TMAO), a uremic metabolite that is elevated in the setting of CKD, has been implicated as a nontraditional risk factor for cardiovascular disease. While association studies have linked elevated plasma levels of TMAO to adverse cardiovascular outcomes, its direct effect on cardiac and smooth muscle function remains to be fully elucidated. We hypothesized that pathological concentrations of TMAO would acutely increase cardiac and smooth muscle contractility. These effects may ultimately contribute to cardiac dysfunction during CKD. High levels of TMAO significantly increased paced, ex vivo human cardiac muscle biopsy contractility (P < 0.05). Similarly, TMAO augmented contractility in isolated mouse hearts (P < 0.05). Reverse perfusion of TMAO through the coronary arteries via a Langendorff apparatus also enhanced cardiac contractility (P < 0.05). In contrast, the precursor molecule, trimethylamine (TMA), did not alter contractility (P > 0.05). Multiphoton microscopy, used to capture changes in intracellular calcium in paced, adult mouse hearts ex vivo, showed that TMAO significantly increased intracellular calcium fluorescence (P < 0.05). Interestingly, acute administration of TMAO did not have a statistically significant influence on isolated aortic ring contractility (P > 0.05). We conclude that TMAO directly increases the force of cardiac contractility, which corresponds with TMAO-induced increases in intracellular calcium but does not acutely affect vascular smooth muscle or endothelial function of the aorta. It remains to be determined if this acute inotropic action on cardiac muscle is ultimately beneficial or harmful in the setting of CKD.NEW & NOTEWORTHY We demonstrate for the first time that elevated concentrations of TMAO acutely augment myocardial contractile force ex vivo in both murine and human cardiac tissue. To gain mechanistic insight into the processes that led to this potentiation in cardiac contraction, we used two-photon microscopy to evaluate intracellular calcium in ex vivo whole hearts loaded with the calcium indicator dye Fluo-4. Acute treatment with TMAO resulted in increased Fluo-4 fluorescence, indicating that augmented cytosolic calcium plays a role in the effects of TMAO on force production. Lastly, TMAO did not show an effect on aortic smooth muscle contraction or relaxation properties. Our results demonstrate novel, acute, and direct actions of TMAO on cardiac function and help lay the groundwork for future translational studies investigating the complex multiorgan interplay involved in cardiovascular pathogenesis during CKD.

Alzheimer's "Prevention" vs. "Risk Reduction": Transcending Semantics for Clinical Practice.

The terms "prevention" and "risk reduction" are often used interchangeably in medicine. There is considerable debate, however, over the use of these terms in describing interventions that aim to preserve cognitive health and/or delay disease progression of Alzheimer's disease (AD) for patients seeking clinical care. Furthermore, it is important to distinguish between Alzheimer's disease prevention and Alzheimer's dementia prevention when using these terms. While prior studies have codified research-based criteria for the progressive stages of AD, there are no clear clinical consensus criteria to guide the use of these terms for physicians in practice. A clear understanding of the implications of each term will help guide clinical practice and clinical research. The authors explore the semantics and appropriate use of the terms "prevention" and "risk reduction" as they relate to AD in clinical practice.