Paraproteinemic Neuropathies.

OBJECTIVE: Coexistence of polyneuropathy and gammopathy is a common but potentially challenging situation in clinical practice. This article reviews the clinical, electrophysiologic, and hematologic phenotypes of the paraproteinemic neuropathies and the diagnostic and treatment strategies for each. LATEST DEVELOPMENTS: Advances in our understanding of the underlying pathophysiology of various paraproteinemic neuropathies and their corresponding phenotypes have identified potential new therapeutic targets. Therapeutic strategies to diminish anti-myelin-associated glycoprotein (MAG) IgM antibodies have shown partial and inconsistent efficacy; however, antigen-specific immune therapy is being investigated as a novel treatment to remove the presumably pathogenic anti-MAG antibody. Advances in genetic and cell signaling studies have resulted in the approval of Bruton tyrosine kinase inhibitors for Waldenström macroglobulinemia. Monoclonal antibodies are being investigated for the treatment of light chain amyloidosis. ESSENTIAL POINTS: Early recognition and treatment of underlying plasma cell disorders improves clinical outcomes in patients with paraproteinemic neuropathy. Despite significant progress, our knowledge regarding underlying mechanisms for paraproteinemic neuropathy is still limited. Clinicians' awareness of clinical phenotypes, electrophysiologic hallmarks, and hematologic findings of the different paraproteinemic neuropathies is crucial to promptly identify and treat patients and to avert misdiagnosis. Multidisciplinary collaboration among specialists, including neurologists and hematologists, is paramount for the optimal treatment of these patients with overlapping conditions.

Reducing body myopathy associated with the LIM2 p.(His123Arg) FHL1 variant.

Reducing body myopathy (RBM) is a rare muscle disorder, with marked presence of characteristic intracytoplasmic aggregates in affected muscle fibers. RBM is associated with FHL1 gene mutations. Clinical presentations of RBM have ranged from early fatal to adult onset progressive muscle weakness. We present herein the clinical, electrodiagnostic, and muscle biopsy findings of a 17-year-old female with progressive muscle weakness and contracture. Muscle biopsy showed atrophic fibers that contained menadione nitroblue tetrazolium (NBT) positive reducing bodies. Genetic testing revealed a variant of uncertain significance in the FHL1 gene at a position known to be pathogenic when substituted by other amino acids (p.His123Arg). This variant was later reclassified as pathogenic.

Development of In-Office Laryngeal Nerve Conduction Studies: Computed Tomography and Cadaveric Study.

OBJECTIVES/HYPOTHESIS: In-office recurrent laryngeal nerve conduction studies (NCSs) are a technique that can potentially provide information about laryngeal innervation. NCS is essential in the management of other neuropathies including carpal tunnel syndrome and spinal cord injury. We hypothesize that laryngeal NCS may have similar utility in managing patients with vocal fold paralysis, atrophy, and neurodegenerative disease. NCSs are technically challenging because they require transcervical stimulation of the recurrent laryngeal nerve (RLN). This study combines radiographic data with cadaveric dissection to describe the anatomic parameters for optimal RLN stimulation. STUDY DESIGN: Radiographic and Cadaveric Study. METHODS: Fifty computed tomography scans were reviewed to determine the dimensions for ideal needle electrode placement. These values were compared to measurements from 12 fresh human cadaveric neck dissections. Ultrasound imaging was utilized in select cases. The neck was dissected to assess the accuracy of electrode placement. RESULTS: Radiographically, the mean transcervical depth to the RLN was 33.2 mm ± 8.3 mm in males versus 29.4 mm ± 9.4 mm in females. The working space between the lateral trachea and carotid artery was 15.3 mm ± 3.6 mm on the right and 14.1 mm ± 2.9 mm on the left. After placement of stimulating electrodes into the cadaveric neck, the electrode tips were consistently within 8 mm of the RLN. Ultrasound guidance improved placement accuracy of the stimulating electrode. CONCLUSIONS: Laryngeal NCSs can provide detailed and objective information about laryngeal innervation that could dramatically improve the management of various neuropathies. In-office NCSs require technical precision, and this study describes anatomic factors that may affect the feasibility of performing this technique. LEVEL OF EVIDENCE: NA Laryngoscope, 131:1566-1569, 2021.

Polyneuropathy Reveals Origins of Decade-long Gastrointestinal Symptoms in a Patient With Undiagnosed Mitochondrial Neurogastrointestinal Encephalopathy Caused by a Novel Mutation.

Mitochondrial neurogastrointestinal encephalopathy (MNGIE) is a rare autosomal recessive disease that manifests with multiorgan presentation characterized by gastrointestinal, extraocular, and both peripheral and central nervous system involvement. MNGIE is caused by mutation in the TYMP (thymidine phosphorylase) gene, resulting in loss of thymidine phosphorylase enzyme activity. This causes its substrates, thymidine and deoxyuridine, to accumulate in tissues and plasma, while also causing secondary alterations in mitochondrial DNA. To date, more than 80 mutations have been reported in this gene. We present herein the clinical, neuroimaging, electrodiagnostic, and molecular findings of a patient with MNGIE caused by a novel homozygous missense mutation (C1175T > G) of the TYMP gene.

In-hospital mortality and coronary procedure use for individuals with dementia with acute myocardial infarction in the United States.

OBJECTIVES: To determine in-hospital mortality differences in individuals with dementia and acute myocardial infarction (AMI) when using invasive coronary procedures. DESIGN: Retrospective cohort study. SETTING: 2009 Nationwide Inpatient Sample. PARTICIPANTS: Individuals admitted with a primary diagnosis of AMI (N = 631,734) to 1,045 hospitals in 44 states during 2009. MEASUREMENTS: Dementia status and procedural use of diagnostic catheterization, percutaneous intervention (PCI), and coronary artery bypass grafts (CABG) as indicated by International Classification of Diseases, Ninth Revision, codes. The primary outcome was in-hospital mortality. Using multivariable analysis adjusted for covariates, associations were made between coronary procedural use in individuals with dementia and in-hospital mortality. Additional multivariable analysis identified the association between utilization of coronary procedures and in-hospital mortality in AMI patients with dementia. RESULTS: Dementia diagnosis (n = 15,335) was associated with greater likelihood of in-hospital mortality (odds ratio (OR) = 1.22, 95% confidence interval (CI) = 1.15-1.29, P < .001) and less use of diagnostic catheterization (OR = 0.37, 95% CI = 0.35-0.40, P < .001), PCI (OR = 0.37, 95% CI = 0.35-0.40, P < .001), and CABG (OR = 0.19, 95% CI = 0.16-0.22, P < .001). There was less likelihood of in-hospital mortality in participants with dementia who received diagnostic catheterization (OR = 0.36, 95% CI = 0.16-0.78, P < .001), PCI (OR = 0.57, 95% CI = 0.47-0.70, P < .001), or CABG (OR = 0.22, 95% CI = 0.08-0.56, P < .001) than in those not receiving respective interventions. CONCLUSION: Dementia is a significant predictor of in-hospital mortality for hospitalized individuals with AMI and is associated with less use of invasive coronary procedures. Beyond differing care patterns for individuals with AMI and dementia, these results indicate that individuals with dementia are at substantially greater risk for in-hospital mortality when they do not receive procedural interventions.