Orphan Peripheral Neuropathies

Abstract

Objectives: Generally, neuropathies of peripheral nerves are a frequent condition (prevalence 2–3%) and most frequently due to alcoholism, diabetes, renal insufficiency, malignancy, toxins, or drugs. However, the vast majority of neuropathies has orphan status. This review focuses on the etiology, frequency, diagnosis, and treatment of orphan neuropathies. Methods: Literature review Results: Rareness of diseases is not uniformly defined but in the US an orphan disease is diagnosed if the prevalence is <1:200000, in Europe if <5:10000. Most acquired and hereditary neuropathies are orphan diseases. Often the causative variant has been reported only in a single patient or family, particularly the ones that are newly detected (e.g. SEPT9, SORD). Among the complex neuropathies (hereditary multisystem disorders with concomitant neuropathies) orphan forms have been reported among mitochondrial disorders (e.g. NARP, MNGIE, SANDO), spinocerebellar ataxias (e,g, TMEM240), hereditary spastic paraplegias (e.g UBAP1), lysosomal storage disease (e.g. Schindler disease), peroxisomal disorders, porphyrias, and other types (e.g. giant axonal neuropathy, Tangier disease). Orphan acquired neuropathies include the metabolic neuropathies (e.g. vitamin-B1, folic acid), toxic neuropathies (e.g. copper, lithium, lead, arsenic, thallium, mercury), infectious neuropathies, immune-mediated (e.g. Bruns-Garland syndrome), and neoplastic/paraneoplastic neuropathies. Conclusions: Though orphan neuropathies are rare per definition they constitute the majority of neuropathies and should be considered as some of them are easy to identify and potentially treatable, as clarification of the underlying cause may contribute to the knowledge about etiology and pathophysiology of these conditions, and as the true prevalence may become obvious only if all ever diagnosed cases are reported.

Predictive Biomarkers of Oxaliplatin-Induced Peripheral Neurotoxicity

“…Several longitudinal studies, including NCS during OXA therapy, have showed a significant progressive decrease in sensory nerve action potentials (SNAPs) and preservation of motor action compound (CMAPs), in keeping with the presence of an axonal sensory neuropathy, and consistent with the clinical symptoms and signs worsening during the treatment [ 17 , 41 , 58 , 59 , 60 , 61 , 62 , 63 , 64 ]. NCS are capable of objectively assessing the extent of peripheral nerve damage and may also facilitate the identification of patients that manifest subclinical peripheral neuropathy prior to the onset of clinically significant neurotoxicity.…”

“…In this line, reductions of the SNAPs of >11.5% in the median nerve between baseline and four cycles of OXA (odds ratio = 5.603, p = 0.031) and of >22.5% in the sural nerve between four and eight cycles of chemotherapy (odds ratio = 5.603, p = 0.031) were independently associated with the risk of developing severe OXAIPN [ 63 ]. However, very recently, negative results were obtained in another study evaluating the role of the sural nerve after administering 25% or 50% of the planned OXA dose in predicting the occurrence of clinically significant OXAIPN in 55 CRC patients [ 59 ]. The assessment of sural nerve instead dorsal sural ( Figure 2 ), and the size of the study could underlie these negative findings.…”

“…The assessment of sural nerve instead dorsal sural ( Figure 2 ), and the size of the study could underlie these negative findings. Long-term longitudinal neurophysiological assessments of OXA-treated patients have revealed a significant recovery of the SNAPs in sensory nerves in some studies [ 58 , 63 , 71 ] but not in other studies [ 59 , 61 ]. The length of follow-up observation may explain these differences.…”

“…Very recently, Kroigard et al identified VDT measure obtained before treatment correlated as a predictor of clinically significant OXAIPN six months post-treatment. However, sensitivity of a baseline VDT < 5 (maximum 8) for the prediction of clinically significant neuropathy six months after treatment was modest (76.0% (95% CI 54.9% to 90.6%)) and specificity was low (53.3% (95% CI 34.3% to 71.7%)) [ 59 ].…”

“…Change of −0.05 °C in CDT had a sensitivity and specificity of 92.3% (95% CI 64.0% to 99.8%) 64.9% (95% CI 47.5% to 79.8%), respectively, in predicting neuropathic pain six months after finishing OXAIPN. For change in HPT and the prediction of neuropathic pain, −0.85 °C had a sensitivity of 64.3% (95% CI 35.1–87.2%) and a specificity of 70.0% (95% CI 53.5–83.4%) [ 59 ]. Conversely, no association in cold and warm thresholds in 35 cancer patients treated with OXA-based regimen and OXAIPN was identified [ 82 ].…”