Daratumumab in first-line treatment of patients with light chain amyloidosis and Mayo stage IIIb improves treatment response and overall survival.

Treatment of patients with Mayo stage IIIb light chain (AL) amyloidosis is still challenging, and the prognosis remains very poor. Mayo stage IIIb patients were excluded from the pivotal trial leading to the approval of daratumumab in combination with bortezomib-cyclophosphamide-dexamethasone. This retrospective, multicenter study evaluates the addition of daratumumab to first-line therapy in patients with newly diagnosed stage IIIb AL amyloidosis.

Corneal confocal microscopy reveals small nerve fibre loss correlating with motor function in adult spinal muscular atrophy.

Background: 5q Spinal muscular atrophy (SMA) is a progressive, inherited, and severely disabling - yet treatable - motor neuron disease. Although treatment options have evolved in recent years, biomarkers for treatment monitoring and prognosis prediction remain elusive. Here, we investigated the utility of corneal confocal microscopy (CCM), a non-invasive imaging technique to quantify small corneal nerve fibres in vivo, as a diagnostic tool in adult SMA.

Corneal confocal microscopy identifies corneal nerve loss and increased Langerhans cells in presymptomatic carriers and patients with hereditary transthyretin amyloidosis.

Background: Hereditary transthyretin amyloidosis (ATTRv amyloidosis) is a rare, but life-threatening protein misfolding disorder due to TTR gene mutations. Cardiomyopathy (ATTRv-CM) and polyneuropathy (ATTRv-PN) with early small nerve fibre involvement are the most common manifestations. Timely diagnosis and treatment initiation are key to limiting progression of disease.

A novel TTR mutation (p.Ala65Val) underlying late-onset hereditary transthyretin (ATTRv) amyloidosis with mixed cardiac and neuropathic phenotype: a case report.

Background: Hereditary transthyretin (ATTRv) amyloidosis is a rare, genetically heterogeneous and phenotypically variable systemic disease characterized by deposition of misfolded transthyretin fibrils in various tissues. ATTRv cardiomyopathy and progressive axonal polyneuropathy are the most common manifestations, leading to severe disability and ultimately death within approximately ten years. As disease-modifying treatment options evolve, timely diagnosis and treatment initiation are crucial to prevent rapid disease progression.

Total Plasma Exchange in Neuromuscular Junction Disorders-A Single-Center, Retrospective Analysis of the Efficacy, Safety and Potential Diagnostic Properties in Doubtful Diagnosis.

Neuromuscular junction disorders (NJDs) are a heterogeneous group of diseases including myasthenia gravis (MG). In some cases, patients are present with myasthenic symptoms without evidence of autoimmune antibodies, making diagnosis challenging. Total plasma exchange (TPE) has proven efficacy in NJDs.

Prevalence and predictors of neurological manifestations in systemic AL amyloidosis.

Introduction: Immunoglobulin light chain (AL) amyloidosis is a life-threatening systemic disease due to plasma cell dyscrasias, which is characterized by amyloid deposition in various tissues. Neurological manifestations, in particular peripheral nervous system involvement, play a major role for quality of life and treatment decisions as frequently potentially neurotoxic drugs are used.

Methods: We retrospectively investigated the prevalence of neurological manifestations, its risk factors and prognostic value in 155 consecutive patients with AL amyloidosis in a single German tertiary center between 2010 and 2021.

Quantitative Tc-DPD-SPECT/CT assessment of cardiac amyloidosis.

Introduction: Transthyretin (ATTR) amyloidosis is responsible for the majority of cardiac amyloidosis (CA) cases and can be reliably diagnosed with bone scintigraphy and the visual Perugini score. We aimed to implement a quantification method of cardiac amyloid deposits in patients with suspected cardiac amyloidosis and to compare performance to visual scoring.

Methods And Materials: 136 patients received Tc-DPD-bone scintigraphy including SPECT/CT of the thorax in case of suspicion of cardiac amyloidosis.

Corneal confocal microscopy to detect early immune-mediated small nerve fibre loss in AL amyloidosis.

Objective: Light chain (AL) amyloidosis is a life-threatening disorder characterised by extracellular deposition of amyloid leading to dysfunction of multiple organs. Peripheral nerve involvement, particularly small fibre neuropathy, may be associated with poorer survival. Corneal confocal microscopy (CCM) is a rapid and non-invasive imaging technique to quantify corneal small nerve fibres and immune cells in vivo.

Clinical features and predictors of atrial fibrillation in patients with light-chain or transthyretin cardiac amyloidosis.

Aims: The study aimed to investigate the prevalence, phenotypic characteristics, and predictors of atrial fibrillation (AF) in patients presenting with cardiac amyloidosis (CA) of light-chain (AL) or transthyretin (ATTR) type.

Methods And Results: Clinical, biochemical, and echocardiographic data of patients presenting with CA between 2005 and 2020 were retrospectively collected. CA staging was based on established biomarker systems.

Assessment of Health-Related Quality of Life in Adult Spinal Muscular Atrophy Under Nusinersen Treatment-A Pilot Study.

5q-Spinal muscular atrophy (SMA) is a severely disabling inherited neuromuscular disease that progressively reduces the motor abilities of affected individuals. The approval of the antisense oligonucleotide nusinersen, which has been shown to improve motor function in adult SMA patients, changed the treatment landscape. However, little is known about its impact on patients' quality of life (QoL), and there is still a need for adequate patient-reported outcome measures.

Assessment of Bulbar Function in Adult Patients with 5q-SMA Type 2 and 3 under Treatment with Nusinersen.

The antisense oligonucleotide nusinersen has been shown to improve trunk and limb motor function in patients with spinal muscular atrophy (SMA). Bulbar dysfunction, which is regularly present in SMA, is not captured by standard motor scores, and validated measurement instruments to assess it have not yet been established. Data on whether and how bulbar function changes under gene-based therapies in adult SMA patients are also unavailable.

Cognitive Impairment in Adult Patients with 5q-Associated Spinal Muscular Atrophy.

In previous studies, a below-average, average, or above-average intelligence quotient (IQ) in children with SMA was detected but, aside from a severe physical disability, the cognitive performance of adult SMA patients has not yet been evaluated. The intelligence test used in this study, the Wechsler Adult Intelligence Scale, fourth edition (WAIS-IV), was used to measure major intelligence components of adult SMA patients. The WAIS-IV determines four index scores representing verbal comprehension, perceptual reasoning, working memory, and processing speed.

Gut bacterial microbiota in patients with myasthenia gravis: results from the MYBIOM study.

Background: Myasthenia gravis (MG) is an autoimmune neuromuscular disease, with gut microbiota considered to be a pathogenetic factor. Previous pilot studies have found differences in the gut microbiota of patients with MG and healthy individuals. To determine whether gut microbiota has a pathogenetic role in MG, we compared the gut microbiota of patients with MG with that of patients with non-inflammatory and inflammatory neurological disorders of the peripheral nervous system (primary endpoint) and healthy volunteers (secondary endpoint).

Impact of time to diagnosis on Mayo stages, treatment outcome, and survival in patients with AL amyloidosis and cardiac involvement.

Objective: To study the impact of time to diagnosis on cardiac Mayo stages, treatment outcome, and overall survival.

Methods: We retrospectively analyzed 77 consecutive patients diagnosed between 2015 and 2020 with AL amyloidosis and cardiac involvement. Medical history was recorded in standardized form with the help of a questionnaire.

Nusinersen treatment in adult patients with spinal muscular atrophy: a safety analysis of laboratory parameters.

Background: Nusinersen is an intrathecally administered antisense oligonucleotide (ASO) that improves motor function in patients with spinal muscular atrophy (SMA). In addition to efficacy, the safety of a therapy is the decisive factor for the success of the treatment. For some ASOs, various organ toxicities have been described, such as thrombocytopenia, renal and liver impairment, or coagulation abnormalities.

Detect it so you can treat it: A case series and proposed checklist to detect neurotoxicity in checkpoint therapy.

Background: Checkpoint inhibitors show impressive and durable responses in various cancer types and provide new avenues for cancer immunotherapy. However, these drugs have a variety of adverse events. Common autoimmune-related adverse effects include fatigue, hepatitis, skin rash, endocrine deficiencies, and colitis.

Genotype-phenotype correlation in a novel ABHD12 mutation underlying PHARC syndrome.

PHARC syndrome is a rare neurodegenerative disorder caused by mutations in the ABHD12 gene. It is a genetically heterogeneous and clinically variable disease, which is characterized by demyelinating polyneuropathy, hearing loss, cerebellar ataxia, retinitis pigmentosa, and early-onset cataract and can easily be misdiagnosed as other neurologic disorders with a similar clinical picture, such as Charcot-Marie-Tooth disease and Refsum disease. We describe the genotype-phenotype correlation of two siblings with a novel genotype underlying PHARC syndrome.

Neurofilament Heavy Chain and Tau Protein Are Not Elevated in Cerebrospinal Fluid of Adult Patients with Spinal Muscular Atrophy during Loading with Nusinersen.

Nusinersen is the first approved drug for the treatment of spinal muscular atrophy (SMA). Treatment of SMA with nusinersen is based on a fixed dosing regimen. For other motoneuron diseases, such as amyotrophic lateral sclerosis (ALS), biomarkers are available for clinical diagnostics; however, no such biomarkers have yet been found for SMA.

Prevalence of hereditary transthyretin amyloid polyneuropathy in idiopathic progressive neuropathy in conurban areas.

Background: Hereditary transthyretin amyloidosis (ATTR amyloidosis) is a rare, genetically heterogenous, and clinically variable autosomal dominant disease that severely reduces life expectancy. As treatment options grow, a proper diagnostic approach is mandatory especially in non-endemic regions with diverse genetic backgrounds.

Methods: We examined 102 neuropathy patients at a German neuromuscular centre.

Multiple blocks of intermittent and continuous theta-burst stimulation applied via transcranial magnetic stimulation differently affect sensory responses in rat barrel cortex.

Key Points: Theta-burst stimulation (TBS) applied via transcranial magnetic stimulation is able to modulate human cortical excitability. Here we investigated in a rat model how two different forms of TBS, intermittent (iTBS) and continuous (cTBS), affect sensory responses in rat barrel cortex. We found that iTBS but less cTBS promoted late (>18 ms) sensory response components while not affecting the earliest response (8-18 ms).