Deciphering compromised speech-in-noise intelligibility in older listeners: the role of cochlear synaptopathy.

Speech intelligibility declines with age and sensorineural hearing damage (SNHL). However, it remains unclear whether cochlear synaptopathy (CS), a recently discovered form of SNHL, significantly contributes to this issue. CS refers to damaged auditory-nerve synapses that innervate the inner hair cells and there is currently no go-to diagnostic test available.

Distinctive clinical features in biopsy-proven nerve large-arteriole vasculitis and microvasculitis.

Vasculitic neuropathy is caused by inflammatory destruction of nerve blood vessels resulting in nerve ischemia. Nerve vasculitis can be divided into two categories based on vessel size - large arteriole vasculitis (≥75 µm) and microvasculitis (<75 µm). Herein, we characterize the clinical features of nerve large-arteriole vasculitis compared to nerve microvasculitis.

Optimizing Anti-Myelin-Associated Glycoprotein and IgM-Gammopathy Testing for Neuropathy Treatment Evaluation.

Background And Objectives: Patients with typical anti-myelin-associated glycoprotein (anti-MAG) neuropathy have IgM-gammopathy, mimic distal chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and are treatment resistant. Anti-MAG patients go unrecognized when IgM-gammopathy is undetected or with atypical phenotypes. We investigated an optimal anti-MAG titration cutoff for excluding CIDP and the impact of IgM-gammopathy detection on neuropathy treatment evaluation without anti-MAG antibodies.

Neurologic Clinical, Electrophysiologic, and Pathologic Characteristics of Primary vs Secondary Neurolymphomatosis.

Background And Objectives: Neurolymphomatosis (NL) is characterized by lymphomatous infiltration of the peripheral nervous system presenting as the initial manifestation of a lymphoma (primary NL [PNL]) or in relapse of a known lymphoma (secondary NL [SNL]). This report details and compares the neurologic clinicopathologic characteristics of these 2 groups.

Methods: This retrospective study was performed on patients diagnosed with pathologically confirmed NL in nerve between January 1, 1992, and June 31, 2020.

Amyloid Neuropathy: From Pathophysiology to Treatment in Light-Chain Amyloidosis and Hereditary Transthyretin Amyloidosis.

Amyloid neuropathy is caused by deposition of insoluble β-pleated amyloid sheets in the peripheral nervous system. It is most common in: (1) light-chain amyloidosis, a clonal non-proliferative plasma cell disorder in which fragments of immunoglobulin, light or heavy chain, deposit in tissues, and (2) hereditary transthyretin (ATTRv) amyloidosis, a disorder caused by autosomal dominant mutations in the TTR gene resulting in mutated protein that has a higher tendency to misfold. Amyloid fibrils deposit in the endoneurium of peripheral nerves, often extensive in the dorsal root ganglia and sympathetic ganglia, leading to atrophy of Schwann cells in proximity to amyloid fibrils and blood-nerve barrier disruption.

Autonomic impairment in primary lateral sclerosis.

Purpose: Prior studies reported evidence of autonomic involvement in motor neuron disease and suggested more severe dysfunction in upper motor neuron predominant syndromes. Hence, we sought to characterize autonomic impairment in primary lateral sclerosis.

Methods: Neurological evaluations, thermoregulatory sweat tests, and autonomic reflex screens were analyzed retrospectively in 34 primary lateral sclerosis patients (28 definite and 6 probable).

Diagnosis and treatment of hereditary transthyretin amyloidosis with polyneuropathy in the United States: Recommendations from a panel of experts.

Hereditary transthyretin (ATTRv; v for variant) amyloidosis is a rare, multisystem, progressive, and fatal disease in which polyneuropathy is a cardinal manifestation. Due to a lack of United States (US)-specific guidance on ATTRv amyloidosis with polyneuropathy, a panel of US-based expert clinicians convened to address identification, monitoring, and treatment of this disease. ATTRv amyloidosis with polyneuropathy should be suspected in unexplained progressive neuropathy, especially if associated with systemic symptoms or family history.

Clinicopathologic Findings in Patients With Paraneoplastic Neuropathies and Antibodies Strongly Associated With Cancer.

Background And Objectives: Pathologic descriptions of peripheral nerve involvement in paraneoplastic neuropathies are sparse, mostly from autopsies focusing on CNS and dorsal root ganglia tissues. Here, we describe the clinicopathologic features of peripheral nerve biopsies in patients with paraneoplastic neurologic syndromes to expand the currently limited knowledge.

Methods: Retrospective review of the Mayo Clinic electronic medical record from 1995 to 2022 for patients identified to have subacute onset neuropathy with paraneoplastic antibodies identified in our neuroimmunology laboratory having available nerve biopsies performed at the time of diagnosis.

Nerve transcriptomes in autoimmune and genetic demyelinating neuropathies: Pathogenic pathway assessment of nerve demyelination.

The pathogenesis of autoimmune demyelinating neuropathies is poorly understood compared to inherited demyelinating forms. We performed whole transcriptome (RNA-Seq) using nerve biopsy tissues of patients with different autoimmune and inherited demyelinating neuropathies (CIDP n = 10, POEMS n = 18, DADS n = 3, CMT1 n = 3) versus healthy controls (n = 6). A limited number of differentially expressed genes compared to healthy controls were identified (POEMS = 125, DADS = 15, CMT = 14, CIDP = 5).

Peripheral Nervous, Hepatic, and Gastrointestinal Endpoints for AL Amyloidosis Clinical Trials: Report from the Amyloidosis Forum Multi-organ System Working Group.

Systemic immunoglobulin light chain (AL) amyloidosis is a heterogeneous rare disease driven by a destructive monoclonal gammopathy and typified by misfolded immunoglobulin light and/or heavy chains which aggregate and deposit in organs as insoluble amyloid fibrils. Disease heterogeneity is driven by the degree of multi-systemic involvement; cardiac, renal, neurological, and gastrointestinal (GI) systems are affected to varying degrees in different patients. While prognosis is primarily driven by hematologic response to treatment and outcomes associated with cardiac events and overall survival, the involvement of the peripheral nervous, hepatic, and GI systems can also have a significant impact on patients.

Hematologic Disorders and the Nervous System.

Objective: This article discusses the epidemiology, diagnosis, treatment, and prevention of neurologic complications of red blood cell, platelet, and plasma cell disorders.

Latest Developments: Cerebrovascular complications can occur in patients with blood cell and platelet disorders. Treatment strategies to prevent stroke are available for patients with sickle cell disease, polycythemia vera, and essential thrombocythemia.

TS-HDS autoantibody: clinical characterization and utility from real-world tertiary care center experience.

Objectives: To evaluate clinical utility of trisulfated-heparin disaccharide (TS-HDS) IgM testing from real-world tertiary care center experience.

Methods: Medical records of patients with positive TS-HDS antibodies who were evaluated at Mayo Clinic from 2009 to 2022 were reviewed.

Results: Seventy-seven patients (50 females) had positive TS-HDS antibody.

3D genome mapping identifies subgroup-specific chromosome conformations and tumor-dependency genes in ependymoma.

Ependymoma is a tumor of the brain or spinal cord. The two most common and aggressive molecular groups of ependymoma are the supratentorial ZFTA-fusion associated and the posterior fossa ependymoma group A. In both groups, tumors occur mainly in young children and frequently recur after treatment.

Reconstruction of Triangular Fibrocartilage Complex Avulsions (Palmar 1C) with Associated Lunotriquetral and Dorsal Capsule Injury: A Case Report.

Case: A 34-year-old farmer and railroad worker injured his left wrist when working at a railroad. The resulting dorsal-ulnar wrist blow caused disabling pain. Splits and 2 subsequent surgeries failed, including an arthroscopic triangular fibrocartilage complex (TFCC) debridement and thermal ablation.

Plexus MRI helps distinguish the immune-mediated neuropathies MADSAM and MMN.

Background: Among immune-mediated neuropathies, clinical-electrophysiological overlap exists between multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) and multifocal motor neuropathy (MMN). Divergent immune pathogenesis, immunotherapy response, and prognosis exist between these two disorders. MRI reports have not shown distinction of these disorders, but biopsy confirmation is lacking in earlier reports.

Proteomic profiling of sporadic late-onset nemaline myopathy.

Objective: To define the proteomic profile of sporadic late-onset nemaline myopathy (SLONM) and explore its pathogenesis.

Methods: We performed mass spectrometry on laser-dissected frozen muscle samples from five patients with SLONM, three of whom with an associated monoclonal protein (MP), and four controls, to determine the proteomic profile of SLONM. Furthermore, we assessed the role of the MP by evaluating the expression of the immunoglobulin light chain variable regions (IGVL).

Standardized Autonomic Testing in Patients With Probable Radiation-Induced Afferent Baroreflex Failure.

Injury of the afferent limb of the baroreflex from neck radiation causes radiation-induced afferent baroreflex failure (R-ABF). Identification and management of R-ABF is challenging. We aimed to investigate the pattern of autonomic dysfunction on standardized autonomic testing in patients with probable R-ABF.

Small Fiber Neuropathy Incidence, Prevalence, Longitudinal Impairments, and Disability.

Background And Objectives: There are limited population-based data on small fiber neuropathy (SFN). We wished to determine SFN incidence, prevalence, comorbid conditions, longitudinal impairments, and disabilities.

Methods: Test-confirmed patients with SFN in Olmsted, Minnesota, and adjacent counties were compared 3:1 to matched controls (January 1, 1998-December 31, 2017).

Neurofascin-155 Immunoglobulin Subtypes: Clinicopathologic Associations and Neurologic Outcomes.

Background And Objective: Multiple studies highlighting the diagnostic utility of neurofascin-155 (NF155)-immunoglobulin G4 (IgG4) in chronic demyelinating inflammatory polyradiculoneuropathy (CIDP) have been published. However, few studies comprehensively address the long-term outcomes or clinical utility of NF155-immunoglobulin M (IgM) or NF155-immunoglobulin G (IgG) in the absence of NF155-IgG4. We evaluated phenotypic and histopathologic specificity and differences in outcomes between these NF155 antibody isotypes or IgG subclasses.

From Single Batch to Mass Production-Automated Platform Design Concept for a Phase II Clinical Trial Tissue Engineered Cartilage Product.

Advanced Therapy Medicinal Products (ATMP) provide promising treatment options particularly for unmet clinical needs, such as progressive and chronic diseases where currently no satisfying treatment exists. Especially from the ATMP subclass of Tissue Engineered Products (TEPs), only a few have yet been translated from an academic setting to clinic and beyond. A reason for low numbers of TEPs in current clinical trials and one main key hurdle for TEPs is the cost and labor-intensive manufacturing process.

Pure Motor Onset and IgM-Gammopathy Occurrence in Multifocal Acquired Demyelinating Sensory and Motor Neuropathy.

Background And Objectives: To longitudinally investigate patients with multifocal acquired demyelinating sensory and motor neuropathy (MADSAM), quantifying timing and location of sensory involvements in motor onset patients, along with clinicohistopathologic and electrophysiologic findings to ascertain differences in patients with and without monoclonal gammopathy of uncertain significance (MGUS).

Methods: Patients with MADSAM seen at Mayo Clinic and tested for monoclonal gammopathy and ganglioside antibodies were retrospectively reviewed (January 1, 2007-December 31, 2018).

Results: Of 76 patients with MADSAM, 53% had pure motor, 16% pure sensory, 30% sensorimotor, and 1% cranial nerve onsets.