Search

Combination therapy has birthed improved treatment possibilities for a number of complex and degenerative diseases in the world, which include cancer, diabetes and cardiovascular disease, and has been encouraged for use in the treatment of Alzheimer's disease (AD), as a result of its complex pathological pathways. The combination of memantine and donepezil was approved for use to treat moderate-to-severe AD cases in 2014. Studies have however continued to investigate many other possible combination therapies for the treatment of AD. This article highlights some of the recent combination therapies involving the use of donepezil. [ABSTRACT FROM AUTHOR]

Long COVID is an emerging problem in the current health care scenario. It is a syndrome with common symptoms of shortness of breath, fatigue, cognitive dysfunction, and other conditions that have a high impact on daily life. They are fluctuating or relapsing states that occur in patients with a history of SARS-CoV-2 infection for at least 2 months. They are usually conditions that at 3 months after onset cannot be explained by an alternative diagnosis. Currently very little is known about this syndrome. A thorough review of the literature highlights that the cause is attributable to deposits of tau protein. Massive phosphorylation of tau protein in response to SARS-CoV-2 infection occurred in brain samples from autopsies of people previously affected with COVID-19. The neurological disorders resulting from this clinical condition are termed tauopathies and can give different pathological symptoms depending on the involved anatomical region of the brain. Peripheral small-fiber neuropathies are also evident among patients with Long COVID leading to fatigue, which is the main symptom of this syndrome. Certainly more research studies could confirm the association between tau protein and Long COVID by defining the main role of tau protein as a biomarker for the diagnosis of this syndrome that is widespread in the post-pandemic period. [ABSTRACT FROM AUTHOR]

Aim of the study : Systematic review and meta-analysis to assess the effectiveness of manual therapy in improving carpal tunnel syndrome (CTS) symptoms, physical function, and nerve conduction studies. Method: MEDLINE, Web of Science, SCOPUS, Cochrane Library, TRIP database, and PEDro databases were searched from the inception to September 2021. PICO search strategy was used to identify randomized controlled trials applying manual therapy on patients with CTS. Eligible studies and data extraction were conducted independently by two reviewers. Methodology quality and risk of bias were assessed by PEDro scale. Outcomes assessed were pain intensity, physical function, and nerve conduction studies. Results: Eighty-one potential studies were identified and six studies involving 401 patients were finally included. Pain intensity immediately after treatment showed a pooled standard mean difference (SMD) of − 2.13 with 95% confidence interval (CI) (− 2.39, − 1.86). Physical function with Boston Carpal Tunnel Syndrome Questionnaire (BCTS-Q) showed a pooled SMD of − 1.67 with 95% CI (− 1.92, − 1.43) on symptoms severity, and a SMD of − 0.89 with 95% CI (− 1.08, − 0.70) on functional status. Nerve conduction studies showed a SMD of − 0.19 with 95% CI (− 0.40, − 0.02) on motor conduction and a SMD of − 1.15 with 95% CI (− 1.36, − 0.93) on sensory conduction. Conclusions: This study highlights the effectiveness of manual therapy techniques based on soft tissue and neurodynamic mobilizations, in isolation, on pain, physical function, and nerve conduction studies in patients with CTS. [ABSTRACT FROM AUTHOR]

Peripheral neuropathy in patients with rheumatoid arthritis is associated with a maladaptive autoimmune response that may cause chronic pain and disability. Nerve conduction studies are the routine method performed when rheumatologists presume its presence. However, this approach is invasive, may not reveal subtle malfunctions in the early stages of the disease, and does not expose abnormalities in structures surrounding the nerves and muscles, limiting the possibility of a timely diagnosis. This work aims to present a narrative review of new technologies for the clinical assessment of peripheral neuropathy in Rheumatoid Arthritis. Through a bibliographic search carried out in five repositories, from 1990 to 2020, we identified three technologies that could detect peripheral nerve lesions and perform quantitative evaluations: (1) magnetic resonance neurography, (2) functional magnetic resonance imaging, and (3) high-resolution ultrasonography of peripheral nerves. We found these tools can overcome the main constraints imposed by the previous electrophysiologic methods, enabling early diagnosis. [ABSTRACT FROM AUTHOR]

Hintergrund: In den letzten Jahren wurde die Therapie zahlreicher Tumorentitäten durch den Einsatz moderner Immuntherapien mit Checkpoint-Inhibitoren revolutioniert. Guten Ansprechraten stehen jedoch zahlreiche immunvermittelte Nebenwirkungen gegenüber. Neurologische immunvermittelte Nebenwirkungen gehören zu den seltenen, jedoch häufig schwer verlaufenden Komplikationen einer Checkpoint-Inhibitor-Therapie.Methode: Es wurde eine systematische Suche in den Datenbanken PubMed und Web of Science nach Fallberichten und Studien zu neurologischen Nebenwirkungen unter Checkpoint-Inhibitor-Therapie durchgeführt.Ergebnisse: Insgesamt 42 Arbeiten zu neurologischen Nebenwirkungen von Checkpoint-Inhibitoren mit insgesamt 85 berichteten Fällen wurden identifiziert. Die häufigsten berichteten neurologischen Nebenwirkungen waren Myopathien, Neuropathien, Erkrankungen der neuromuskulären Endplatte und Enzephalitiden. Die höchste Morbidität und Mortalität wiesen Enzephalopathien und Myopathien mit begleitender Myokarditis auf.Schlussfolgerung: Vor dem Hintergrund eines rasch zunehmenden Einsatzes von Checkpoint-Inhibitoren gibt diese Arbeit einen Überblick über bislang berichtete klinische Verlaufsformen neurologischer Nebenwirkungen. Kontrollierte Studien zur Therapie neurologischer Nebenwirkungen fehlen. Fallberichte lassen vermuten, dass eine frühzeitige Steroidtherapie die Wahrscheinlichkeit einer kompletten Remission der neurologischen Symptome erhöht. Typische Symptomkonstellationen müssen daher schnell erkannt und eine immunsuppressive Therapie eingeleitet werden. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting toxicity of several commonly used chemotherapy drugs including taxanes, vinca alkaloids, and platinum compounds. Development of CIPN is highly variable, both in self-reported symptoms and functional consequences, and can be severe enough to alter dose intensity. Purpose: To describe the natural histories of both patient-reported symptoms of CIPN and functional impairments in breast cancer patients undergoing taxane-based chemotherapy. Methods: Thirty-three breast cancer patients (32 female/1 male; 47.8 ± 11.2 years; n = 17 stage II/ n = 16 stage III) were enrolled. Patients completed self-reports of symptoms and function (e.g., EORTC QLQ-CIPN20) and objective measures of physical function (i.e., balance and gait testing) in an outpatient oncology clinic at five timepoints: (1) baseline-prior to starting chemotherapy, (2-4) before starting subsequent chemotherapy cycles, and (5) 1-3 months after receiving their last taxane infusion. Results: Significant negative changes in both patient-reported outcomes and objective functional measures were observed. Decreased balance was observed after the first chemotherapy cycle (28% increase in medial-lateral excursion of the center of pressure, p = 0.016) and progressed with cumulative exposure (43% increase, p < 0.001). Patients also demonstrated slower walking speeds (5% decrease, p = 0.003) as they progressed through treatment. These functional deficits were mirrored with increased patient-reported symptom severity for all EORTC QLQ-CIPN20 subscales (all p < 0.05). Conclusion: This study longitudinally assessed patient-reported outcomes concurrently with balance and gait testing in patients undergoing taxane therapy. Taxane treatment was associated with the development of clinically relevant problems in both CIPN symptoms and patient function. [ABSTRACT FROM AUTHOR]

The retina (a peripheral link of the visual analyzer) is a complex system whose adequate functioning is necessary for normal functioning of the eye. The loss of any cell type in the retina resulting from some diseases or trauma destroys complex neuronal chains that play a key role in the control of visual function. To gain an insight into the mechanisms underlying different pathological processes in the retina, which lead in humans to hereditary or acquired loss of vision, modeling of the corresponding pathological states in experiments on laboratory animals is used. Achievements in molecular and cellular biology led to significant progress in the development of new techniques for therapy of different visual disturbances. In the literature, techniques for neurotrophic and gene therapy used in experiments have been described. The successful use of techniques of gene therapy in experiments on laboratory animals allowed researchers to initiate phase-I clinical trials of treatment of retinoblastoma, age-related macular degeneration, and Leber's congenital amaurosis. It this review, we discuss the possibilities for application of gene therapy to a wider range of eye diseases. [ABSTRACT FROM AUTHOR]

The neuromuscular system can be involved in several systemic conditions. Clinical manifestations can appear at onset or throughout the course of the disease process. New investigational methods, including imaging of peripheral nerves, new laboratory tests, and antibodies, are available. In addition to symptomatic therapies, specific treatment options, such as for familial amyloid neuropathy and Fabry's disease, are becoming increasingly available. Pathomechanisms vary depending on the underlying disease process. In addition to metabolic, hormonal, immune, and antibody-mediated mechanisms, in some generalized diseases, genetic causes need to be considered. This review focuses on different aspects of the peripheral nervous system including the nerve roots, plexuses, mononeuropathies and generalized neuropathies, neuromuscular junction disorders, muscle, and autonomic nervous system. [ABSTRACT FROM AUTHOR]

Schwann cells are the myelinating glial cells of the peripheral nervous system and establish myelin sheaths on large caliber axons in order to accelerate their electrical signal propagation. Apart from this well described function, these cells revealed to exhibit a high degree of differentiation plasticity as they were shown to re- and dedifferentiate upon injury and disease as well as to actively participate in regenerative- and inflammatory processes. This review focuses on the crosstalk between glial- and immune cells observed in many peripheral nerve pathologies and summarizes functional evidences of molecules, regulators and factors involved in this process. We summarize data on Schwann cell's role presenting antigens, on interactions with the complement system, on Schwann cell surface molecules/receptors and on secreted factors involved in immune cell interactions or para-/autocrine signaling events, thus strengthening the view for a broader (patho) physiological role of this cell lineage. [ABSTRACT FROM AUTHOR]

Involvement of the peripheral nervous system in mitochondrial disorders (MD) has been previously reported. However, the exact prevalence of peripheral neuropathy and/or myopathy in MD is still unclear. In order to evaluate the prevalence of neuropathy and myopathy in MD, we performed sensory and motor nerve conduction studies (NCS) and concentric needle electromyography (EMG) in 44 unselected MD patients. NCS were abnormal in 36.4% of cases, and were consistent with a sensori-motor axonal multineuropathy (multifocal neuropathy), mainly affecting the lower limbs. EMG evidence of myopathy was present in 54.5% of patients, again mainly affecting the lower limbs. Nerve and muscle involvement was frequently subclinical. Peripheral nerve and muscle involvement is common in MD patients. Our study supports the variability of the clinical expression of MD. Further studies are needed to better understand the molecular basis underlying the phenotypic variability among MD patients. [ABSTRACT FROM AUTHOR]

The IgG molecule is the main component of IVIg. Commercial preparations of IVIg are derived from a pool of donors and subsequently, IVIg products contain smaller amounts of IgA and IgM antibodies as well as Th2 cytokines and cytokine antagonists that may also contribute to therapeutic effects. Numerous targets for IVIg include: T-cells, cytokines, immune cell trafficking, B-cells, complement and Fc-receptors. IVIg has been demonstrated to inactivate auto-reactive T-cells by competing for and interrupting their interaction with antigen presenting cells. The balance of cytokines also appears to be restored by IVIg, with studies showing that IVIg contains antibodies and antagonists to pro-inflammatory cytokines. In addition, IVIg is thought to interfere with and prevent the passage of auto-immune T-cells into the blood–nerve barrier. The effects of exogenous antibodies on B-cells have been well studied; IVIg is thought to down-regulate antibody production by B-cells, interfere with B-cell proliferation via a blockade of cell surface receptors and prevent the activation of certain subtypes of B-cell. In addition, IVIg can affect innate immunity by interrupting the steps in the complement activation cascade and blocking Fc-receptor mediated activity, which results in down-regulation of macrophage activity. In conclusion, IVIg has numerous modes of action, which culminate in the down-regulation of the immune response; many of which may be relevant to neuromuscular disorders and immune neuropathies. [ABSTRACT FROM AUTHOR]

Surgical access to the inguinal region, notably during hernia repairs, exposes the ilioinguinal nerve to the risk of damage at the origin of the neuralgia. The incidence of these post-operative neuropathies and their medicolegal consequences justify this study about the anatomical variations of the ilioinguinal nerve. With the aim of preventing its damage during repairs of groin hernias and identifying the factors of onset of chronic spontaneous neuropathy of the ilioinguinal nerve, we dissected 100 inguinal regions of 51 fresh adult corpses. The nerve was absent in seven cases and double in one case. Out of the 94 ilioinguinal nerves observed, we analyzed the path in relation to the inguinal ligament and the connections with the walls of the inguinal canal and its content. The ilioinguinal nerve travels along the superficial surface of the internal oblique muscle, passing on average 1.015 cm from the inguinal ligament. In one case, the fibers of the internal oblique muscle spanned it in several places. The nerve was antero-funicular in 78.72% of cases and perforated the fascia of the external oblique in 28.72% of cases. The terminal division took place in the inguinal canal in 86% of cases, with terminal branches that sometimes perforated the fascia of the external oblique. These results enabled us to better understand the etiopathogenic aspects of certain neuropathies of the groin and to propose techniques useful for the protection of the nerve during repairs of groin hernias. [ABSTRACT FROM AUTHOR]

Familial amyloidotic polyneuropathy (FAP) is a late-onset inherited disease characterized by the deposition of amyloid fibrils. FAP is associated with mutations on the transthyretin (TTR) gene. A monoclonal antibody, MAb 39-44, reacting with high molecular weight aggregates of TTR but not with tetrameric TTR has recently been generated and characterized. This antibody recognizes a cryptic epitope that is expressed in isolated recombinant amyloidogenic mutants and in ex vivo amyloid. In the present work we show that this amyloid-specific antibody specifically recognizes in a direct enzyme-linked immunoassay (ELISA) plasma TTR from carriers of various mutations associated with FAP, both in asymptomatic individuals and in patients. In contrast, it does not react with plasma TTR from healthy individuals or that from carriers of nonpathogenic mutations. Using the ELISA developed in this study we identified three different TTR mutations in Portuguese patients with neuropathy of unknown cause, later shown to have amyloid tissue deposition. This antibody recognizes conformations that express cryptic epitopes shared by amyloidogenic TTR variants associated with FAP, not present among nonpathogenic TTR molecules. This antibody will contribute to further identify and characterize intermediates of the amyloidogenic cascade. In addition, it will also be useful for screening amyloidogenic TTR mutations in patients with neuropathy of unknown cause, prior to precise molecular diagnosis using protein and/or DNA analysis. [ABSTRACT FROM AUTHOR]

Muscle hypertrophy is rare in denervating diseases. A patient with calf enlargement associated with L5-S1 radiculopathy and another with thenar, hypothenar, forearm and calf muscle hypertrophy in the course of chronic relapsing inflammatory demyelinating polyneuropathy are described. Gastrocnemius muscle biopsy revealed both type I and type II fibre hypertrophy in the former case and predominant type I fibre hypertrophy in the latter. Passive stretching and abnormal spontaneous muscular activity might have played a role in the origin of hypertrophy in both patients, but a satisfactory explanation for denervation hypertrophy has yet to be provided. [ABSTRACT FROM AUTHOR]

Chronic immune-mediated neuropathies, including chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), neuropathies associated with monoclonal gammopathy, and multifocal motor neuropathy (MMN), are a group of disorders deemed to be caused by an immune response against peripheral nerve antigens. Several immune therapies have been reported to be variably effective in these neuropathies including steroids, plasma exchange, and high-dose intravenous (IVIg) or subcutaneous (SCIg) immunoglobulins. These therapies are however far from being invariably effective and may be associated with a number of side effects leading to the use of immunosuppressive agents whose efficacy has not been so far confirmed in randomized trials. More recently, new biological agents, such as rituximab, have proved to be effective in patients with neuropathy associated with IgM monoclonal gammopathy and are currently tested in CIDP. [ABSTRACT FROM AUTHOR]

Critical illness polyneuromypathy has not previously been reported as a complication of diabetic coma. We describe a patient with hyperosmolar non-ketotic coma (HONK) complicating gram-negative sepsis in whom persistent coma and profound tetraplegia caused considerable concern. Although, initially, it was feared that the patient had suffered a central neurological complication such as stroke or cerebral oedema, a diagnosis of critical illness motor syndrome (CIMS) was subsequently confirmed neurophysiologically. Profound limb weakness associated with HONK is not necessarily due to a catastrophic cerebral event, rather it may be a result of CIMS, which has an excellent prognosis for full neurological recovery. [ABSTRACT FROM AUTHOR]