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Brain : a Journal of Neurology Nov 2023Valid, responsive blood biomarkers specific to peripheral nerve damage would improve management of peripheral nervous system (PNS) diseases. Neurofilament light chain...
Valid, responsive blood biomarkers specific to peripheral nerve damage would improve management of peripheral nervous system (PNS) diseases. Neurofilament light chain (NfL) is sensitive for detecting axonal pathology but is not specific to PNS damage, as it is expressed throughout the PNS and CNS. Peripherin, another intermediate filament protein, is almost exclusively expressed in peripheral nerve axons. We postulated that peripherin would be a promising blood biomarker of PNS axonal damage. We demonstrated that peripherin is distributed in sciatic nerve, and to a lesser extent spinal cord tissue lysates, but not in brain or extra-neural tissues. In the spinal cord, anti-peripherin antibody bound only to the primary cells of the periphery (anterior horn cells, motor axons and primary afferent sensory axons). In vitro models of antibody-mediated axonal and demyelinating nerve injury showed marked elevation of peripherin levels only in axonal damage and only a minimal rise in demyelination. We developed an immunoassay using single molecule array technology for the detection of serum peripherin as a biomarker for PNS axonal damage. We examined longitudinal serum peripherin and NfL concentrations in individuals with Guillain-Barré syndrome (GBS, n = 45, 179 time points), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP, n = 35, 70 time points), multiple sclerosis (n = 30), dementia (as non-inflammatory CNS controls, n = 30) and healthy individuals (n = 24). Peak peripherin levels were higher in GBS than all other groups (median 18.75 pg/ml versus < 6.98 pg/ml, P < 0.0001). Peak NfL was highest in GBS (median 220.8 pg/ml) and lowest in healthy controls (median 5.6 pg/ml), but NfL did not distinguish between CIDP (17.3 pg/ml), multiple sclerosis (21.5 pg/ml) and dementia (29.9 pg/ml). While peak NfL levels were higher with older age (rho = +0.39, P < 0.0001), peak peripherin levels did not vary with age. In GBS, local regression analysis of serial peripherin in the majority of individuals with three or more time points of data (16/25) displayed a rise-and-fall pattern with the highest value within the first week of initial assessment. Similar analysis of serial NfL concentrations showed a later peak at 16 days. Group analysis of serum peripherin and NfL levels in GBS and CIDP patients were not significantly associated with clinical data, but in some individuals with GBS, peripherin levels appeared to better reflect clinical outcome measure improvement. Serum peripherin is a promising new, dynamic and specific biomarker of acute PNS axonal damage.
Topics: Humans; Peripherins; Intermediate Filaments; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Guillain-Barre Syndrome; Axons; Biomarkers; Dementia; Multiple Sclerosis
PubMed: 37435933
DOI: 10.1093/brain/awad234 -
Journal of Clinical Medicine Jul 2023Carpal tunnel syndrome (CTS) is a condition that affects the main nerves in the wrist area that causes numbness, tingling, and weakness in the hand and arm. CTS affects... (Review)
Review
Carpal tunnel syndrome (CTS) is a condition that affects the main nerves in the wrist area that causes numbness, tingling, and weakness in the hand and arm. CTS affects 5% of the general population and results in pain in the wrist due to repetitive use, most commonly affecting women and office workers. Conservative management of CTS includes neurodynamic modulation to promote median nerve gliding during upper limb movements to maintain normal function. However, evidence for the benefits of neurodynamic modulation found disparities, and hence, the effectiveness of neurodynamic modulation remains unclear. This study aimed to systematically review the current evidence from randomized controlled trials (RCTs) to establish the effectiveness of neurodynamic techniques as a non-surgical treatment option for CTS. Using the PRISMA guidelines, two authors searched four electronic databases, and studies were included if they conformed to pre-established eligibility criteria. Primary outcome measures included outcomes from the Boston carpal tunnel syndrome questionnaire, while secondary outcomes included nerve conduction velocity, pain, and grip strength. Quality assessment was completed using the Cochrane RoB2 form, and a meta-analysis was performed to assess heterogeneity. Twelve RCTs met our inclusion/exclusion criteria with assessments on 1003 participants in the treatment and control arms. High heterogeneity and some risks of bias were observed between studies, but the results of the meta-analysis showed a significant reduction in our primary outcome, the Boston carpal tunnel syndrome questionnaire-symptom severity scale (mean difference = -1.20, 95% CI [-1.72, -0.67], < 0.00001) and the Boston carpal tunnel syndrome questionnaire-functional severity scale (mean difference = -1.06, 95% CI [-1.53, -0.60], < 0.00001). Secondary outcomes such as sensory and motor conduction velocity increased significantly, while motor latency was significantly reduced, all positively favoring neurodynamic techniques. Pain was also significantly reduced, but grip strength was not significantly different. Our systematic review demonstrates significant benefits of neurodynamic modulation techniques to treat CTS and specifically that it reduces symptom severity, pain, and motor latency, while at the same time improving nerve conduction velocities. Hence, our study demonstrates a clear benefit of neurodynamic techniques to improve recovery CTS.
PubMed: 37568290
DOI: 10.3390/jcm12154888