Causes of neuropathy in patients referred as “idiopathic neuropathy”

Farhad, Khosro; Traub, Rebecca; Ruzhansky, Katherine; Brannagan, Thomas H.

doi:10.1002/mus.24969

Cited by 78 publications

(62 citation statements)

References 40 publications

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“…Thus, we hypothesized that common factors such as the metabolic syndrome, elevated plasma 1-deoxySLs and microangiopathy might contribute to both conditions. Previous studies indicate a higher prevalence of metabolic risk factors such as IGT [6, 7], hypercholesterolemia [5], hypertriglyceridemia [4, 5], abdominal obesity and arterial hypertension [3] in CIAP-patients. We found a non-significant trend towards a higher occurrence of the metabolic syndrome in CIAP patients compared to healthy controls.…”

Section: Discussionmentioning

confidence: 99%

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Metabolic Syndrome, Neurotoxic 1-Deoxysphingolipids and Nervous Tissue Inflammation in Chronic Idiopathic Axonal Polyneuropathy (CIAP)

et al. 2017

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AimChronic idiopathic axonal polyneuropathy (CIAP) is a slowly progressive, predominantly sensory, axonal polyneuropathy, with no aetiology being identified despite extensive investigations. We studied the potential role of the metabolic syndrome, neurotoxic 1-deoxysphingolipids (1-deoxySLs), microangiopathy and inflammation in sural nerve biopsies.MethodsWe included 30 CIAP-patients, 28 with diabetic distal symmetrical polyneuropathy (DSPN) and 31 healthy controls. We assessed standardised scales, tested for the metabolic syndrome, measured 1-deoxySLs in plasma, performed electroneurography and studied 17 sural nerve biopsies (10 CIAP; 7 DSPN).ResultsOne third of the CIAP-patients had a metabolic syndrome, significantly less frequent than DSPN-patients (89%). Although the metabolic syndrome was not significantly more prevalent in CIAP compared to healthy controls, hypercholesterolemia did occur significantly more frequent. 1-deoxySLs were significantly and equally elevated in both patient groups compared to healthy controls. Mean basal lamina thickness of small endoneurial vessels and the number of CD68- or CD8-positive cells in biopsies of CIAP- and DSPN-patients did not differ significantly. However, the number of leucocyte-common-antigen positive cells was significantly increased in CIAP.ConclusionsA non-significant trend towards a higher occurrence of the metabolic syndrome in CIAP-patients compared to healthy controls was found. 1-deoxySLs were significantly increased in plasma of CIAP-patients. Microangiopathy and an inflammatory component were present in CIAP-biopsies.

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Section: Discussionmentioning

confidence: 99%

“…Recent studies suggested that disorders in lipid and glucose metabolism, known as the metabolic syndrome [2], are more prevalent in CIAP-patients [3–6]. Further arguing for a metabolic source is the clinical similarity of CIAP to diabetic distal symmetrical polyneuropathy (DSPN) [3].…”

Section: Introductionmentioning

confidence: 99%

Metabolic Syndrome, Neurotoxic 1-Deoxysphingolipids and Nervous Tissue Inflammation in Chronic Idiopathic Axonal Polyneuropathy (CIAP)

et al. 2017

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“…In contrast, the MGH iiSFPN cohort had a 5.5% prevalence by A1c (Table 2). Two other idiopathic neuropathy cohorts had higher rates of undiagnosed diabetes, e.g., 13% in Utah [60] and 9.2% in New York [19], but two others were lower, 1.7% in Michigan [7], and 3% in New York [13], so the overall importance of undiagnosed diabetes as a contributor to initially idiopathic SFPN remains uncertain. These prevalence differences might reflect social or demographic differences or different care patterns, so decisions on whether and how to test for undiagnosed diabetes should be made locally.…”

Section: Discussionmentioning

confidence: 99%

“…The second largest group of SFPN patients, comprising 20–50% in recent series [19, 22, 26, 51, 69], is those with “initially idiopathic” or cryptogenic causes (here abbreviated as iiSFPN). They are the focus of the current study.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic value of blood tests for occult causes of initially idiopathic small-fiber polyneuropathy

2016

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Small-fiber polyneuropathy (SFPN) causes non-specific symptoms including chronic pain, cardiovascular, gastrointestinal, and sweating complaints. Diagnosis is made from history and exam in patients with known risk factors such as diabetes, but objective test confirmation is recommended for patients without known risks. If tests confirm SFPN, and it is “initially idiopathic” (iiSFPN), screening for occult causes is standard. This study’s aim was to evaluate the 21 widely available, recommended blood tests to identify the most cost-effective ones and to learn about occult causes of iiSFPN. Records were reviewed from all 213 patients with SFPN confirmed by distal-leg skin biopsy, nerve biopsy, or autonomic-function testing in our regional center during 2013. We determined the prevalence of each abnormal blood-test result (ABTR) in the iiSFPN cohort, compared this to population averages, and measured the costs of screening subjects to obtain one ABTR. Participants were 70% female and 43.0±18.6 years old. High erythrocyte sedimentation rate (ESR) and antinuclear antibody (ANA; ≥1:160 titer) were each present in 28% of subjects. The ABTR ≥ 3× more prevalent in iiSFPN than in the total population were high ESR, high ANA, low C3, Sjögren’s and celiac autoantibodies. Together, these suggest the possibility of a specific association between iiSFPN and dysimmunity. ATR identifying diabetes, prediabetes, and hypertriglyceridemia were less common in iiSFPN than in the population and thus not associated with iiSFPN here. Reimbursement for the 6 most cost-effective iiSFPN-associated blood tests–ESR, ANA, C3, autoantibodies for Sjögren’s and celiac, plus thyroid-stimulating hormone–was $99.57/person with 45.6% sensitivity for detecting one abnormal result. Angiotensin-converting enzyme was elevated in 45% but no patients had sarcoidosis, so this test was futile here.

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“…Alternatively, classification based on clinical phenotype has also been proposed 49. Despite extensive evaluation, 20-50% of cases of SFN are ultimately classified as idiopathic 50515253. The most common causes include diabetes, immunologic conditions, sodium channel mutations, and vitamin B12 deficiency 29.…”

Section: Differential Diagnosis Of Small Fiber Neuropathiesmentioning

confidence: 99%

Diagnosis and management of sensory polyneuropathy

Gwathmey

Pearson

2019

BMJ

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Sensory polyneuropathies, which are caused by dysfunction of peripheral sensory nerve fibers, are a heterogeneous group of disorders that range from the common diabetic neuropathy to the rare sensory neuronopathies. The presenting symptoms, acuity, time course, severity, and subsequent morbidity vary and depend on the type of fiber that is affected and the underlying cause. Damage to small thinly myelinated and unmyelinated nerve fibers results in neuropathic pain, whereas damage to large myelinated sensory afferents results in proprioceptive deficits and ataxia. The causes of these disorders are diverse and include metabolic, toxic, infectious, inflammatory, autoimmune, and genetic conditions. Idiopathic sensory polyneuropathies are common although they should be considered a diagnosis of exclusion. The diagnostic evaluation involves electrophysiologic testing including nerve conduction studies, histopathologic analysis of nerve tissue, serum studies, and sometimes autonomic testing and cerebrospinal fluid analysis. The treatment of these diseases depends on the underlying cause and may include immunotherapy, mitigation of risk factors, symptomatic treatment, and gene therapy, such as the recently developed RNA interference and antisense oligonucleotide therapies for transthyretin familial amyloid polyneuropathy. Many of these disorders have no directed treatment, in which case management remains symptomatic and supportive. More research is needed into the underlying pathophysiology of nerve damage in these polyneuropathies to guide advances in treatment.

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Causes of neuropathy in patients referred as “idiopathic neuropathy”

Abstract: The major causes of undiagnosed neuropathies were impaired glucose metabolism, CIDP, and monoclonal gammopathies. Despite thorough evaluation 32.7% remained idiopathic. Muscle Nerve 53: 856-861, 2016.

Cited by 78 publications

References 40 publications

Metabolic Syndrome, Neurotoxic 1-Deoxysphingolipids and Nervous Tissue Inflammation in Chronic Idiopathic Axonal Polyneuropathy (CIAP)

Metabolic Syndrome, Neurotoxic 1-Deoxysphingolipids and Nervous Tissue Inflammation in Chronic Idiopathic Axonal Polyneuropathy (CIAP)

Diagnostic value of blood tests for occult causes of initially idiopathic small-fiber polyneuropathy

Diagnosis and management of sensory polyneuropathy

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