Wild-type Transthyretin Amyloid Deposition in an Ascending Aortic Aneurysm.

Amyloid deposition in aortic tissue is associated with increased stiffness. We report a patient with ascending aortic aneurysm and chronic abdominal aortic dissection who had significant wild-type transthyretin amyloid deposition on surgical pathology. The patient did not have cardiac involvement on further workup.

A study concept of expeditious clinical enrollment for genetic modifier studies in Charcot-Marie-Tooth neuropathy 1A.

BACKGROUND: Caused by duplications of the gene encoding peripheral myelin protein 22 (PMP22), Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common hereditary neuropathy. Despite this shared genetic origin, there is considerable variability in clinical severity. It is hypothesized that genetic modifiers contribute to this heterogeneity, the identification of which may reveal novel therapeutic targets. In this study, we present a comprehensive analysis of clinical examination results from 1564 CMT1A patients sourced from a prospective natural history study conducted by the RDCRN-INC (Inherited Neuropathy Consortium). Our primary objective is to delineate extreme phenotype profiles (mild and severe) within this patient cohort, thereby enhancing our ability to detect genetic modifiers with large effects. METHODS: We have conducted large-scale statistical analyses of the RDCRN-INC database to characterize CMT1A severity across multiple metrics. RESULTS: We defined patients below the 10th (mild) and above the 90th (severe) percentiles of age-normalized disease severity based on the CMT Examination Score V2 and foot dorsiflexion strength (MRC scale). Based on extreme phenotype categories, we defined a statistically justified recruitment strategy, which we propose to use in future modifier studies. INTERPRETATION: Leveraging whole genome sequencing with base pair resolution, a future genetic modifier evaluation will include single nucleotide association, gene burden tests, and structural variant analysis. The present work not only provides insight into the severity and course of CMT1A, but also elucidates the statistical foundation and practical considerations for a cost-efficient and straightforward patient enrollment strategy that we intend to conduct on additional patients recruited globally.

Approach to Peripheral Neuropathy for the Primary Care Clinician.

Peripheral neuropathy is commonly encountered in the primary care setting and is associated with significant morbidity, including neuropathic pain, falls, and disability. The clinical presentation of neuropathy is diverse, with possible symptoms including weakness, sensory abnormalities, and autonomic dysfunction. Accordingly, the primary care clinician must be comfortable using the neurologic examination-including the assessment of motor function, multiple sensory modalities, and deep tendon reflexes-to recognize and characterize neuropathy. Although the causes of peripheral neuropathy are numerous and diverse, careful review of the medical and family history coupled with limited, select laboratory testing can often efficiently lead to an etiologic diagnosis. This review offers an approach for evaluating suspected neuropathy in the primary care setting. It will describe the most common causes, suggest an evidence-based workup to aid in diagnosis, and highlight recent evidence that allows for selection of symptomatic treatment of patients with neuropathy.

Brain complexity increases in mania.

An important challenge in measuring whole brain activation is to develop a measure that could distinguish between normal and abnormal mood states. The application of chaos theory and non-linear dynamics to problems in biological sciences has resulted in a growing body of advancements and the notion of brain as a complex, non-linear system has attracted physicists, mathematicians, biologists and psychologists alike. To search for a correlation between alterations in chaotic brain states and mood disorders, we compared the fractal dimension of the electroencephalographic (EEG) signal in patients going through a manic episode of bipolar mood disorder (BMD) type I to a control group of healthy adults and showed that the EEG fractal dimension is significantly augmented in our patients. Thus, for the first time, we draw a clear objective distinction between normal and abnormal mood and associated brain states.