Paraproteinemic neuropathies.

The diagnostic evaluation of a peripheral neuropathy includes testing for the presence of monoclonal gammopathy, which can be found in about 10% of patients with peripheral neuropathy. Our role, as physicians, is to determine whether the neuropathy is directly related to the gammopathy or whether the co-occurrence of these two disorders is purely coincidental. The evaluating physician needs to be familiar with the different types of neuropathies associated with monoclonal gammopathies, their clinical and electrodiagnostic characteristics, and their appropriate diagnostic evaluation and management. Testing for monoclonal protein disorders includes serum protein electrophoresis (SPEP) and immunofixation of blood, and in some cases of urine, as well as measurement of free light chains and quantitative immunoglobulins. Specific antibody testing is directed by paraprotein type and neuropathy phenotype. Patients with abnormal free light chains in association with sensory and autonomic neuropathy should be evaluated for AL amyloidosis. When a lambda monoclonal protein is identified together with a clinical phenotype of chronic inflammatory demyelinating neuropathy (CIDP), a diagnosis of polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, skin changes (POEMS) syndrome should be considered. Patients with IgM paraprotein associated neuropathy should be assessed for distal acquired demyelinating sensorimotor (DADS) neuropathy, with or without anti myelin associated glycoprotein (MAG) antibody or CANOMAD syndrome. In many cases, a monoclonal gammopathy of uncertain significance (MGUS) is incidental and unrelated to the neuropathy. Collaboration with oncology is critical in evaluating patients with monoclonal proteins to assess for underlying plasma cell neoplasms or B cell lymphomas.

Hereditary Transthyretin Amyloidosis Polyneuropathy.

In the last decade, we have witnessed dramatic improvements in the diagnosis, workup, management, and monitoring of patients with hereditary transthyretin amyloidosis (ATTRv). Updated imaging techniques (e.g., 99mTc-PYP scan) are increasingly being used in place of tissue biopsies for confirmation of disease. Novel treatments now include antisense oligonucleotide and RNA interference drugs, whereas new applications such as CRISPR and amyloid antibodies are being studied for potential use in the future. These treatments have dramatically improved quality of life and increased survival in patients with ATTRv. Despite these breakthroughs, many challenges remain. Some of these challenges include early recognition and diagnosis of ATTRv, monitoring and initiation of treatment in asymptomatic or paucisymptomatic carriers, adequate treatment in people with mixed phenotype (i.e., cardiac and neurological), and the emergence of new phenotypes in people living longer with the disease (i.e., central nervous system and ocular complications). Research in those areas of deficit is ongoing, and in the future, we may have preventive therapies, better biomarkers, more efficient therapies for organs that we cannot currently target, and enhanced diagnostic techniques with the help of novel imaging techniques and artificial intelligence. In this review, we will summarize the current knowledge about polyneuropathy related to ATTRv and its management, discuss methods to improve early diagnosis and monitoring, and discuss emerging trends.

A Multifactor Approach to Mild Cognitive Impairment.

Mild cognitive impairment (MCI) represents an intermediate stage between normal cognition and dementia. Individuals with MCI are at increased risk of conversion to dementia, and the rate of progression of MCI to dementia is dependent on age, gender, and education. MCI may be diagnosed using neuropsychological criteria using cut-offs representing decrements in cognition, or using criteria to assess for a decline in functional status. The ability to determine the status of dementia-related biomarkers has allowed for better staging and prognostication in different forms of MCI. MCI is now recognized as a significant target stage for future therapies. These future therapies aim to reduce the rate of conversion of individuals with MCI to dementia. In this article, we review different conceptions of MCI, the diagnosis and prognostication of MCI, and presently available management approaches for this condition.

Treatment characteristics of patients with hereditary transthyretin amyloidosis: a cohort study.

BACKGROUND: There are novel medications approved for the treatment of hereditary transthyretin amyloidosis (ATTRv), classified as transthyretin (TTR) stabilizers or gene silencers. While many patients may be on both classes of medications, there is no data available on the safety and efficacy of combination therapy. OBJECTIVES: To describe ATTRv patient and TTR-targeted therapy characteristics in a US cohort, and compare outcomes with combination therapy versus monotherapy. METHODS: We performed a retrospective cohort study with electronic health record data of patients with ATTRv seen at a single institution between January 2018 and December 2022. We collected data on symptomatology, gene mutation, disease severity, ATTRv treatment, hospitalizations, and mortality. RESULTS: One hundred sixty-two patients with ATTRv were identified. The average age at diagnosis was 65 years. 86 patients (53%) had the V122I variant. 119 patients were symptomatic, of whom 103 were started on ATTRv-specific treatment. 41 patients (40%) had cardiomyopathy only, and 53 (51%) had a mixed phenotype of cardiomyopathy and neuropathy. 38 patients (37%) received therapy with both a gene silencer and protein stabilizer. 9 patients (15%) in the monotherapy group had two or more cardiac hospitalizations after starting treatment, compared to 3 patients (9%) on combination therapy (p=0.26). The adjusted hazard ratio of all-cause mortality for the patients on combination therapy compared to monotherapy was 0.37 (0.08-1.8, p=0.21). CONCLUSIONS: While the efficacy is unproven, over one-third of patients with ATTRv are on both a stabilizer and a silencer. There were no safety issues for combination therapy. There was a trend towards improved hospitalizations and survival in patients in the combination group but this was not statistically significant. Larger studies with longer follow-up are necessary to determine benefit of combination therapy.

Bilateral pneumothorax as possible atypical presentation of coronavirus disease 2019 (COVID-19).

Coronavirus disease 2019 (COVID-19) is most frequently associated with a mild presentation of fever, cough, and shortness of breath. Typical radiographic findings of COVID-19 are bilateral ground-glass opacities on computed tomography (CT) scans. However, there have been instances of pneumothorax, giant bulla, and pneumomediastinum, mainly in elderly COVID-19 patients and predominately occurring at least one week after symptom onset. Here, we report a case where a healthy, young Hispanic man presented with three days of fever, cough, and dyspnea. On admission to the emergency department, he was found to have bilateral pneumothoraces, pneumomediastinum, and pneumopericardium requiring bilateral chest tubes. The patient had no predisposing risk factors for pneumothorax, such as a history of trauma, smoking, past intubations, asthma, high pressure oxygen delivery, or a history of prior pneumothorax. The only positive diagnostic test was a SARS-CoV-2 test by real-time reverse transcriptase-polymerase chain reaction assay. This case highlights the potential atypical presentation of a COVID-19 infection and is the first reported case, to our knowledge, that features bilateral spontaneous pneumothoraces, pneumomediastinum, and pneumopericardium as a probable rare presentation of COVID-19.

Real-Time Medical Video Denoising with Deep Learning: Application to Angiography.

This paper describes the design, training, and evaluation of a deep neural network for removing noise from medical fluoroscopy videos. The method described in this work, unlike the current standard techniques for video denoising, is able to deliver a result quickly enough to be used in real-time scenarios. Furthermore, this method is able to produce results of a similar quality to the existing industry-standard denoising techniques.