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Hereditary and Metabolic Diseases of the Central Nervous System in Adults
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
MT-ATP6 is the only gene associated with NARP. Not all clinical cases have a detectable deletion. Clinical findings include: Proximal muscle weakness.Sensory neuropathy.Ataxia.Retinal pigmentary degeneration.
Topical Pain Medications and Their Role in Pain Management
Published in Sahar Swidan, Matthew Bennett, Advanced Therapeutics in Pain Medicine, 2020
Barton et al.29 performed a double-blind, placebo-controlled trial of a combination topical pain gel to investigate its effect on chemotherapy-induced neuropathic pain. The compounded cream contained 10 mg baclofen/40 mg amitriptyline HCl/20 mg ketamine. The researchers measured outcomes based on three components of sensory neuropathy: sensory (i.e., numbness, tingling, burning sensation in the hands and feet), motor (i.e., ability to hold a pen, opening jars, and cramping), and autonomic (i.e., erectile dysfunction, dizziness, vision). This study confirmed that the combination gel trended toward more improvement in sensory neuropathy. Higher doses of the combination gel (30 mg baclofen/60 mg amitriptyline/30 mg ketamine formulation) were initially proposed, but due to a lack of data on the systemic absorption of the triple combination, the FDA approved an investigational new drug application for this combination with the lower dose cream that was used in this trial. The researchers point out that the lower doses may have been associated with less effectiveness.
Sandhoff disease/GM2 gangliosidosis/deficiency of Hex A and Hex B subunit deficiency
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
Adult-onset patients may have psychiatric symptoms [14]. They have included confusion, emotional lability and intermittent psychosis. Decline in cognitive function was found in 44 percent of patients. Ataxia and an apparent spinocerebellar picture may be evident [10–15]. Dysarthria may be severe. The disorder may be very slowly progressive. Sensory neuropathy was a predominant finding in one family [15]. In late-onset patients, typical membranous cytoplasmic bodies have been reported in the myenteric plexus [16].
First-line treatment of multiple myeloma in both transplant and non-transplant candidates
Published in Expert Review of Anticancer Therapy, 2023
Albert Oriol, Laura Abril, Gladys Ibarra
MoAbs have a relatively favorable safety profile, which makes them interesting for elderly and frail adults. MAIA and ALCYONE trials enrolled a significant proportion of patients over 75 years and demonstrated a PFS benefit in that subgroup of individuals [3,33]. The main safety concerns of the DRD combination are neutropenia, pneumonia, and anemia. All of them are likely to be reduced with preventive measures or early treatment. In contrast, VRD in the SWOG-S0777 trial produced a high rate of neuropathy or worsening of prior neuropathy (35%), associated to the use of intravenous bortezomib [23]. VRD was of marginal benefit for patients aged ≥65 years, in contrast with differences found in the global cohort or in younger patients [24]. A single-center, single-arm study enrolling transplant-ineligible adults with NDMM, evaluated reduced-intensity lenalidomide, subcutaneous bortezomib, and dexamethasone (RVD-lite), and obtained substantial efficacy, with a median PFS 41.9 months after 60-month follow-up. Although sensory neuropathy was observed in 62% of patients, it was rarely grade ≥3 [93]. These results have not been confirmed in a larger trial.
Possible roles of mitochondrial dysfunction in neuropathy
Published in International Journal of Neuroscience, 2021
Chutikorn Khuankaew, Passakorn Sawaddiruk, Poomarin Surinkaew, Nipon Chattipakorn, Siriporn C. Chattipakorn
Neuropathy is a pathological pain in which the function of the nervous system has been disturbed [1,2]. Neuropathy is commonly found with different underlying pathophysiological conditions, including trauma-induced neuropathy, chemotherapy-induced neuropathy, diabetes-induced neuropathy and HIV-associated sensory neuropathy. Neuropathy may affect the sensory, motor or autonomic nervous system which causes suffering in many patients [1,2]. Sensory neuropathy may present neuropathic pain with abnormal sensations such as numbness or changes in the ability to detect heat and cold, whereas muscle weakness, cramps or paralysis are found in patients with motor neuropathy [1]. In addition, autonomic neuropathy may result in abnormal feelings such as dizziness and fainting due to sudden changes in blood pressure, abnormal sweating, incontinence or impotence [2]. The exact pathophysiology of neuropathy is still unclear. Although currently neuropathy cannot be cured, symptomatic therapy has been used to relieve pain in these patients. It is expected that the underlying aetiology of neuropathy should be identified to be targeted for the future therapy.
Opening eyes to therapeutic perspectives of bioactive polyphenols and their nanoformulations against diabetic neuropathy and related complications
Published in Expert Opinion on Drug Delivery, 2021
Rubiya Khursheed, Sachin Kumar Singh, Sheetu Wadhwa, Monica Gulati, Bhupinder Kapoor, Ankit Awasthi, Arya Kr, Rajan Kumar, Faheem Hyder Pottoo, Vijay Kumar, Harish Dureja, Krishnan Anand, Dinesh Kumar Chellappan, Kamal Dua, K. Gowthamarajan
It is estimated that 25% of the diabetic patients use to develop DFU, which further increases the risk of amputation and higher mortality rate. DN is one of the major factors responsible for the development of DFU and accounts for 85% cases of DFU [132]. A joint UK-US study in 1999 explored that the most common combination of factors leading to DFU was peripheral neuropathy, trauma, and foot deformity [133]. Sensory neuropathy results in reduction/loss of sensitivity on the foot surface. In motor neuropathy, loss of balance occurs between flexor and extensor muscles which further develops abnormal pressure, and leads to development of callus. Autonomic neuropathy decreases the supply of blood to the feet thus reducing the moisture content, and formation of cracks. The developed callus (in motor neuropathy) along with loss of sensation (in sensory neuropathy) and reduced moistness (in autonomic neuropathy) gets disrupted and leads to development of DFU. In contrast to acute wounds (maintained at homeostasis), DFUs, if left untreated in the initial phases, may lead to amputations [134].