The diagnostic usefulness of the combined COMPASS 31 questionnaire and electrochemical skin conductance for diabetic cardiovascular autonomic neuropathy and diabetic polyneuropathy

The study investigated the diagnostic performance for diabetic cardiovascular autonomic neuropathy (CAN) and diabetic polyneuropathy (DPN) of the combined use of composite autonomic symptom score (COMPASS) 31, validated questionnaire for autonomic symptoms of CAN, and electrochemical skin conductance (ESC), proposed for detecting DPN and CAN. One‐hundred and two participants with diabetes (age 57 ± 14 years, duration 17 ± 13 years) completed the COMPASS 31 before assessing cardiovascular reflex tests (CARTs), neuropathic symptoms, signs, vibratory perception threshold (VPT), thermal thresholds (TT), and ESC using Sudoscan. Two patterns were evaluated: (a) the combined abnormalities in both tests (COMPASS 31+ESC), and (b) the abnormality in COMPASS 31 and/or ESC (COMPASS 31 and/or ESC). CAN (≥ 1 abnormal CART) and confirmed CAN (≥ 2 abnormal CARTs) were present in 28.1% and 12.5%, DPN (two abnormalities among symptoms, signs, VPT, and TT) in 52%, abnormal COMPASS 31 (total weighted score >16.44) in 48% and abnormal ESC (hands ESC <50 μS and/or feet ESC <70 μS) in 47.4%. Both the patterns—COMPASS 31+ESC and COMPASS 31 and/or ESC—were associated with CAN and DPN (P < .01). COMPASS 31 and ESC reached a sensitivity of 75% and 83% for confirmed CAN, and a specificity of 65% and 67% for DPN. When combining the tests, the sensitivity for CAN rose by up to 100% for CAN and the specificity up to 89% for DPN. The combination of the tests can allow a stepwise screening strategy for CAN, by suggesting CAN absence with combined normality, and prompting to CARTs with combined abnormality.     

There is No Association between Cardiovascular Autonomic Dysfunction and Peripheral Neuropathy in Chronic Hemodialysis Patients

Background and Purpose

The potential association between the severity of autonomic dysfunction and peripheral neuropathy has not been extensively investigated, with the few studies yielding inconsistent results. We evaluated the relationship between autonomic dysfunction and peripheral neuropathy in chronic hemodialysis patients in a cross-sectional study.

Methods

Cardiovascular autonomic function was assessed in 42 consecutive patients with chronic renal failure treated by hemodialysis, using a standardized battery of 5 cardiovascular reflex tests. Symptoms of autonomic dysfunction and of peripheral neuropathy were evaluated using the Autonomic Neuropathy Symptom Score (ANSS) and the Neuropathy Symptoms Score. Neurological deficits were assessed using the Neuropathy Disability Score. Conduction velocities along the sensory and motor fibers of the sural and peroneal nerves were measured. Thermal thresholds were documented using a standardized psychophysical technique.

Results

Parasympathetic and sympathetic dysfunction was prevalent in 50% and 28% of cases, respectively. Peripheral neuropathy was identified in 25 cases (60%). The prevalence of peripheral neuropathy did not differ between patients with impaired (55%) and normal (75%) autonomic function (p=0.297; Fisher''s exact test). The electrophysiological parameters for peripheral nerve function, neuropathic symptoms, abnormal thermal thresholds, age, gender, and duration of dialysis did not differ significantly between patients with and without autonomic dysfunction. Patients with autonomic dysfunction were more likely to have an abnormal ANSS (p=0.048). The severity of autonomic dysfunction on electrophysiological testing was positively correlated with ANSS (r=0.213, p=0.036).

Conclusions

The present data indicate that although cardiovascular autonomic dysfunction is prevalent among patients with chronic renal failure, it is not associated with the incidence of peripheral neuropathy.     

Clinical and electrophysiologic attributes as predictors of results of autonomic function tests

Autonomic dysfunction is a feature of some neuropathies and not others. It has been suggested that some clinical and electrophysiologic attributes are predictable of autonomic impairment detected using laboratory testing; however, clear guidelines are unavailable. We evaluated 138 relatively unselected patients with peripheral neuropathy who underwent neurologic evaluation, electromyography (EMG), nerve conduction studies, and autonomic function tests to determine which variables were predictive of laboratory findings of autonomic failure. The variables evaluated were 1) clinical somatic neuropathic findings, 2) clinical autonomic symptoms, and 3) electrophysiologic findings. Autonomic symptoms were strongly predictive (R _s =0.40, p<0.001) of autonomic failure. Among the non-autonomic indices, absent ankle reflexes were mildly predictive (R _s =0.19, p=0.022) of autonomic impairment, but all others were not (duration, clinical pattern, severity, weakness, sensory loss). Electrophysiologic changes of an axonal neuropathy predicted autonomic impairment while demyelinating neuropathy did not. We conclude that autonomic studies will most likely be abnormal in patients who have symptoms of autonomic involvement and those who have an axonal neuropathy.     

Autonomic neuropathy in patients with HIV: Course, impact of disease stage, and medication

The purpose of this article is to examine the prevalence, degree, and natural course of pupillary neuropathy (PANP), cardiovascular autonomic neuropathy (CANP), and sensorimotor neuropathy (SNP) and to study the impact of disease stage and medication on neuropathy in 61 consecutive patients with HIV. PANP, CANP, and SNP were assessed by standardized test procedures. Overall prevalence of PANP, CANP, and SNP were 66%, 15%, and 15%, respectively. The maximal pupillary area (pupillary measure, p<0.0001) and the lying-to-standing ratio (cardiovascular measure, p<0.0001) were abnormal as compared with control subjects. The changes in CD4+ T-lymphocytes and respiratory sinus arrhythmia percentile during 2 years of follow-up correlated significantly (r=0.758, p=0.007). Patients with CANP were more often in an advanced disease stage than patients without CANP (p=0.004). SNP, but not PANP or CANP, was associated with the intake of the neuropathogenic drugs dideoxycytidine, dideoxyinosine, and 2,3 didehydro-2,3 dideoxythymidine (p<0.05). Autonomic and sensorimotor neuropathy are frequent in patients with HIV, and progression of CANP may put patients at risk for unexpected cardiorespiratory arrest.     

Skin biopsy reveals generalized small fibre neuropathy in hypermobile Ehlers–Danlos syndromes

Background and purpose

Ehlers–Danlos syndromes are hereditary disorders of connective tissue that are characterized by joint hypermobility, skin hyperextensibility and tissue fragility. The most common subtype is the hypermobile type. In addition to symptoms of small fibre neuropathy (SFN) due to damage to the small peripheral nerve fibres, with degeneration of the distal nerve endings, autonomic disorders such as postural tachycardia syndrome (PoTS) are frequently reported features in patients with hypermobile Ehlers–Danlos syndrome (hEDS). To date, the underlying pathophysiological mechanisms are still not completely understood.

Study Purpose

To better understand pathophysiological mechanisms of small fiber neuropathy and autonomic neuropathy in hypermobile Ehlers-Danlos Syndromes.

Methods

We prospectively investigated 31 patients with hEDS compared to 31 healthy controls by using skin biopsy, quantitative sensory testing, tilt-table testing, the painDetect, Small Fibre Neuropathy Screening List and the COMPASS-31 (Composite Autonomic Symptom Score 31) questionnaire.

Results

Nineteen (61%) patients with hEDS were diagnosed with SFN, and 10 (32%) fulfilled the criteria for PoTS. Patients with hEDS had significantly higher heart rates than controls. According to quantitative sensory testing, these patients had generalized thermal and tactile hypesthesia. Skin biopsy revealed significantly reduced intraepithelial nerve fibre density proximally (thigh) and distally (lower leg) in patients compared to controls. This was consistent with various complaints of pain and sensory disturbances in both the proximal and distal body regions.

Conclusion

These results confirm histologically proven SFN as a common feature in patients with hEDS, revealing a generalized distribution of nerve fibre loss. Regarding the frequently reported autonomic and neuropathic dysfunctions, the findings support SFN as an important, but not the only, underlying pathomechanism.     

Incidence of nonamyloidogenic mutations in the transthyretin gene in patients with autonomic and small fiber neuropathy

Introduction: Mutations of the transthyretin (TTR) gene have been associated with polyneuropathy; the protein product has a tendency to form amyloid deposits in the peripheral nervous system. Methods: Patients with small fiber neuropathy (SFN) with or without autonomic symptoms were given skin biopsies to assess nerve fiber density. Any patient with autonomic symptoms was assessed for autonomic neuropathy (AN). If testing revealed no clear cause of neuropathy, the TTR gene was sequenced. Results: Thirty‐six percent of patients were found to harbor at least 1 mutation in the TTR gene sequence (variants of unknown significance [VUS]). Of 24 patients diagnosed with SFN, 8% of patients had a point mutation (c76G>A). Of those patients who were diagnosed with both SFN and AN, 68% of patients had a VUS within the TTR gene (c76G>A, c337‐18G>C). Conclusions: The results suggest an association between presumed nonamyloidogenic mutations in the TTR gene and the development of AN and SFN. Muscle Nerve 57 : 140–142, 2017     

Small and large fiber sensory polyneuropathy in type 2 diabetes: Influence of diagnostic criteria on neuropathy subtypes

Diabetic polyneuropathy (DPN) can be classified based on fiber diameter into three subtypes: small fiber neuropathy (SFN), large fiber neuropathy (LFN), and mixed fiber neuropathy (MFN). We examined the effect of different diagnostic models on the frequency of polyneuropathy subtypes in type 2 diabetes patients with DPN. This study was based on patients from the Danish Center for Strategic Research in Type 2 Diabetes cohort. We defined DPN as probable or definite DPN according to the Toronto Consensus Criteria. DPN was then subtyped according to four distinct diagnostic models. A total of 277 diabetes patients (214 with DPN and 63 with no DPN) were included in the study. We found a considerable variation in polyneuropathy subtypes by applying different diagnostic models independent of the degree of certainty of DPN diagnosis. For probable and definite DPN, the frequency of subtypes across diagnostic models varied from: 1.4% to 13.1% for SFN, 9.3% to 21.5% for LFN, 51.4% to 83.2% for MFN, and 0.5% to 14.5% for non‐classifiable neuropathy (NCN). For the definite DPN group, the frequency of subtypes varied from: 1.6% to 13.5% for SFN, 5.6% to 20.6% for LFN, 61.9% to 89.7% for MFN, and 0.0% to 6.3% for NCN. The frequency of polyneuropathy subtypes depends on the type and number of criteria applied in a diagnostic model. Future consensus criteria should clearly define sensory functions to be tested, methods of testing, and how findings should be interpreted for both clinical practice and research purpose.     

Risks for sensorimotor peripheral neuropathy and autonomic neuropathy in non-insulin-dependent diabetes mellitus (NIDDM)

Identification of risk factors for development of diabetic sensorimotor peripheral neuropathy (DSPN) and diabetic autonomic neuropathy (DNA) may help to prevent or modify these complications. The ABCD Trial, a prospective study of diabetic complications, has identified risk factors of the presence and staging of peripheral neuropathy based on neurological symptom scores, neurological disability scores, autonomic function testing and quantitative sensory examination. DSPN is independently associated with diabetes duration [odds ratio (OR) = 1.5 per 10 years], body weight (OR = 1.1 per 5 kg), age (OR = 1.8 per 10 years), retinopathy (OR = 2.3), overt albuminuria (OR = 2.5), height (OR = 1.2 per 10 cm), duration of hypertension (OR = 1.1 per 10 years), insulin use (OR = 1.4), and race/ethnicity [African American vs. non-Hispanic white (OR = 0.4) and Hispanic vs. non-Hispanic white (OR = 0.8)]. DAN is independently associated with diabetes duration (OR = 1.2 per 10 years), body weight (OR = 1.1 per 5 kg), glycosylated hemoglobin (OR = 1.1 per 2.5%), overt albuminuria (OR = 1.6), and retinopathy (OR = 1.8). © 1998 John Wiley & Sons, Inc. Muscle Nerve, 21: 72–80, 1998.     

Clinical and pathology characterization of small nerve fiber neuro(no)pathy in cerebellar ataxia with neuropathy and vestibular areflexia syndrome

Background and purpose

Biallelic mutation/expansion of the gene RFC1 has been described in association with a spectrum of manifestations ranging from isolated sensory neuro(no)pathy to a complex presentation as cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS). Our aim was to define the frequency and characteristics of small fiber neuropathy (SFN) in RFC1 disease at different stages.

Methods

RFC1 cases were screened for SFN using the Neuropathic Pain Symptom Inventory and Composite Autonomic Symptom Score 31 questionnaires. Clinical data were retrospectively collected. If available, lower limb skin biopsy samples were evaluated for somatic epidermal and autonomic subepidermal structure innervation and compared to healthy controls (HCs).

Results

Forty patients, median age at onset 54 years (interquartile range [IQR] 49–61) and disease duration 10 years (IQR 6–16), were enrolled. Mild-to-moderate positive symptoms (median Neuropathic Pain Symptom Inventory score 12.1/50, IQR 5.5–22.3) and relevant autonomic disturbances (median Composite Autonomic Symptom Score 31 37.0/100, IQR 17.7–44.3) were frequently reported and showed scarce correlation with disease duration. A non-length-dependent impairment in nociception was evident in both clinical and paraclinical investigations. An extreme somatic denervation was observed in all patients at both proximal (fibers/mm, RFC1 cases 0.0 vs. HCs 20.5, p < 0.0001) and distal sites (fibers/mm, RFC1 cases 0.0 vs. HCs 13.1, p < 0.0001); instead only a slight decrease was observed in cholinergic and adrenergic innervation of autonomic structures.

Conclusions

RFC1 disease is characterized by a severe and widespread somatic SFN. Skin denervation may potentially represent the earliest feature and drive towards the suspicion of this disorder.     

Assessment of autonomic function in a cohort of patients with ANCA-associated vasculitis

Objective

To assess symptoms and objective parameters of autonomic dysfunction (AD) in patients with ANCA-associated vasculitides.

Methods

Symptoms and objective parameters of AD were assessed in patients with ANCA-associated vasculitis and in age-matched healthy controls. Autonomic symptoms were explored by COMPASS31, a validated questionnaire addressing symptoms of six autonomic domains (orthostatic, vasomotor, secretomotor, gastrointestinal, pupillomotor, and bladder dysfunction). Objective autonomic parameters consisted of expiratory/inspiratory (E/I) ratio during the deep breathing test (DBT), blood pressure response to cold pressor test (CPT), and skin conductance changes during mental arithmetic.

Results

27 patients and 27 healthy controls have been enrolled. 27 patients and 27 controls completed COMPASS31. 21 patients and 18 controls underwent objective autonomic testing. Vasculitis patients had significantly higher COMPASS31 total scores than controls (median 10.4 vs 3.0; p = 0.005). In the sub-domain analysis, significant differences were seen in the vasomotor and the bladder domain (p = 0.004; p < 0.001, respectively). No correlation was found between COMPASS31 score and disease duration, number of affected organs, or Birmingham vasculitis activity score (BVAS). There was no significant difference in any of the objective autonomic parameters between patients and controls. In a subgroup analysis, no difference in objective autonomic parameters was found between patients with active disease (n = 12) and patients in remission (n = 7).

Conclusion

Patients with ANCA-associated vasculitides commonly have symptoms of autonomic dysfunction that are independent of disease duration and disease severity. However, at least in this single-centre observation, there was no evidence of impaired autonomic regulation in three autonomic function tests in vasculitis patients.

     

Analysis of autonomic outcomes in APOLLO,a phase III trial of the RNAi therapeutic patisiran in patients with hereditary transthyretin-mediated amyloidosis

Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive, debilitating disease often resulting in early-onset, life-impacting autonomic dysfunction. The effect of the RNAi therapeutic, patisiran, on autonomic neuropathy manifestations in patients with hATTR amyloidosis with polyneuropathy in the phase III APOLLO study is reported. Patients received patisiran 0.3 mg/kg intravenously (n = 148) or placebo (n = 77) once every 3 weeks for 18 months. Patisiran halted or reversed polyneuropathy and improved quality of life from baseline in the majority of patients. At baseline, patients in APOLLO had notable autonomic impairment, as demonstrated by the Composite Autonomic Symptom Score-31 (COMPASS-31) questionnaire and Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire autonomic neuropathy domain. At 18 months, patisiran improved autonomic neuropathy symptoms compared with placebo [COMPASS-31, least squares (LS) mean difference, − 7.5; 95% CI: − 11.9, − 3.2; Norfolk QOL-DN autonomic neuropathy domain, LS mean difference, − 1.1; − 1.8, − 0.5], nutritional status (modified body mass index, LS mean difference, 115.7; − 82.4, 149.0), and vasomotor function (postural blood pressure, LS mean difference, − 0.3; − 0.5, − 0.1). Patisiran treatment also led to improvement from baseline at 18 months for COMPASS-31 (LS mean change from baseline, − 5.3; 95% CI: − 7.9, − 2.7) and individual domains, orthostatic intolerance (− 4.6; − 6.3, − 2.9) and gastrointestinal symptoms (− 0.8; − 1.5, − 0.2). Rapid worsening of all study measures was observed with placebo, while patisiran treatment resulted in stable or improved scores compared with baseline. Patisiran demonstrates benefit across a range of burdensome autonomic neuropathy manifestations that deteriorate rapidly without early and continued treatment.

     

An advanced approach for the assessment of gastric motor function in long-term Type 1 diabetes mellitus with and without autonomic neuropathy

Gastric motor dysfunction is a frequent and deleterious long-term complication in diabetes mellitus (DM) but the exact contribution of diabetic autonomic dysfunction remains unclear. The aim of this study was to assess indices of gastric motor function in long-term Type 1 DM in the light of the presence and absence of autonomic neuropathy by means of an advanced dynamic scintigraphic technique. Gastric scintigraphy with condensed images of a short dynamic sequence was applied to 27 long-term Type 1 diabetic patients (duration > 10 years) and 15 control subjects. Two indices of gastric peristalsis, the frequency of contractions (FC) and amplitude of contractions (AC), were assessed scintigraphically together with half-time of gastric emptying (t 1/2). Five cardiac reflex tests were performed to study electrocardiogram (ECG)-based cardiac autonomic neuropathy (CAN). Mean AC was significantly decreased in diabetic patients compared to control subjects (13 ± 9 % vs. 28 ± 8 %, p < 0.005). Mean FC was comparable between diabetic patients and control subjects (3.1 ± 0.4 min⁻¹ vs. 3.1 ± 0.2 min⁻¹). Compared to control subjects, half-time of gastric emptying was significantly prolonged in diabetic patients (31 ± 17 min vs. 20 ± 3 min, p < 0.001). Mean AC, FC and t 1/2 did not differ significantly between diabetic patients with (n = 10) and without (n = 17) ECG-based CAN. Our study demonstrates that in both long-term Type 1 DM with and without autonomic neuropathy, the amplitude but not the frequency of gastric contractions, is frequently reduced. A delay of gastric emptying in Type 1 DM is confirmed although it was independent from the presence of cardiac autonomic neuropathy (CAN). Analyzing gastric motor function with dynamic scintigraphic techniques using condensed images is a promising clinical approach to further elucidate the mechanisms of impaired gastric motility in DM. Received: 25 July 2001, Accepted: 27 March 2002     

The symptoms of autonomic dysfunction in HIV-positive Africans

Background

Human immunodeficiency virus (HIV) infection is associated with autonomic neuropathy. The resultant autonomic dysfunction impairs quality of life and can have fatal consequences. Our aim was to clearly define the symptoms of autonomic dysfunction in African HIV-positive patients and determine whether these symptoms were related with (a) autonomic reflex responses (b) the degree of immunosupression.

Methods

Thirty-one HIV-positive treatment-naïve African patients (mean CD4 cell count 269.5 ± 253.4/mm³) and 12 healthy controls completed a detailed questionnaire (Autonomic System Profile, Mayo Clinic, Rochester, MN) relating to specific symptoms of autonomic dysfunction. After completion of the questionnaire, subjects underwent a standard battery of autonomic reflex tests.

Results

The autonomic symptom score was higher in the male HIV-positive patients (26.7 ± 14.7 points) and female patients with CD4 <200/mm³ (24.7 ± 18.0) than sex-matched controls (male controls, 9.9 ± 6.8, P < 0.05; female controls, 8.8 ± 10.1; P < 0.05). Six patients had scores indicative of severe autonomic dysfunction (>43.8 points). The most common autonomic symptoms were: orthostatic intolerance, secretomotor and gastrointestinal dysfunction. There was no relationship between CD4 cell counts and autonomic symptom scores. The blood pressure response to sustained handgrip was blunted, but all other cardiovascular reflex tests were within the normal range or borderline.

Conclusion

African HIV-positive patients report symptoms of autonomic dysfunction, despite normal or borderline autonomic reflex responses.

     

Assessing diabetic polyneuropathy in Spanish-speaking patients: Translation and validation of the Toronto Clinical Neuropathy Score

Background and Aims

Diabetic sensorimotor polyneuropathy (DSP) is a common complication of diabetes. The Toronto Clinical Neuropathy Score (TCNS) is a useful tool for detecting DSP. However, it is not available in Spanish. The study aimed to translate and culturally adapt the TCNS and modified (mTCNS) scales into Spanish and evaluate their measurement properties.

Methods

A multistep forward-backward method was used for translation and cultural adaptation. A panel of physicians subjected the final Spanish versions of TCNS and mTCNS (TCÑS, mTCÑS) to cognitive debriefing. Consecutive patients with diabetes mellitus and DSP were recruited from an outpatient clinic, and the TCÑS and mTCÑS were tested for construct validity, along with other measures.

Results

The internal consistency of both TCÑS and mTCÑS was excellent, as evidenced by Cronbach's Alpha coefficients of 0.83 and 0.85, respectively. Furthermore, there was a robust positive correlation between TCÑS and mTCÑS. In addition, TCÑS was found to exhibit a strong negative correlation with sural sensory nerve action potential amplitude (r = −0.9206) and peroneal compound motor action potential amplitude (r = −0.729), while demonstrating a positive and strong correlation with the Michigan Neuropathy Screening Instrument (r = 0.713).

Interpretation

The TCÑS and mTCÑS are reliable and valid translations of the original TCNS. The TCÑS and mTCÑS can be used to diagnose and measure the severity of neuropathy in Spanish-speaking patients with diabetes.     

The value of autonomic testing in postural tachycardia syndrome

Abstract Postural tachycardia syndrome (POTS) is a fairly common condition that may or may not be associated with autonomic neuropathy. In a retrospective analysis, we compared two groups of patients based on clinical and autonomic criteria, those with POTS in isolation (POTS-Alone), and POTS with evidence of autonomic neuropathy (POTS-AN). Of 260 records reviewed, 57 patients met the criteria for POTS; 38 (67%) patients assigned to the POTS-Alone group and 19 (33%) patients assigned to the POTS-AN group. A decreased sweat output on the quantitative sudomotor axon reflex test is the most frequent abnormal finding in the POST-AN group suggesting sympathetic cholinergic neuropathy. Clinically, headache and gastrointestinal symptoms were more frequent among the POTS-AN group. Therefore, POTS may exist in isolation and may differ from those associated with AN.This work presented at the 55^th annual meeting of the Annual Academy of Neurology, Honolulu, Hawaii, March 2003.     

Erectile dysfunction as a sentinel symptom of cardiovascular autonomic neuropathy in heavy drinkers

Because autonomic neuropathy (AN) is not routinely assessed in chronic alcoholism, its features and relationship with other disease parameters remain undefined. The very existence of true alcohol-related autonomic dysfunction, in the absence of alcoholic hepatopathy, is even controversial. We aimed this study at evaluating the frequency and pattern of AN in a population of heavy drinkers without liver dysfunction. We also investigated the putative risk factors for AN as well as its relationship to peripheral neuropathy (PN). Autonomic function was evaluated in 70 detoxified alcoholics and 70 well-matched controls by heart-rate response to deep breathing, heart-rate response to standing from lying position, and blood pressure response to standing up. PN was assessed by electroneurography (ENG). Detailed information about sensorimotor and autonomic symptoms, nutritional status, and parameters reflecting alcohol intake were recorded. No patients showed signs of caloric/protein malnutrition. PN was found in 74% and AN (abnormal test results in two of three tests performed) in 26%; abnormalities in at least one autonomic test were found in 62%. All patients with PN were symptomatic, mainly due to sensory disturbances. In line with this, ENG abnormalities were more evident at sural nerves. AN was symptomatic in 10 of 18 patients, and its sole clinical expression was impotence: indeed, the pattern of autonomic involvement was mainly parasympathetic. AN did not correlate with PN, nor with any parameter reflecting the amount of alcohol intake; only performances on heart-rate response to standing from lying position were related to the duration of abuse. The lack of correlation between PN and AN may suggest a different pathophysiology for these two complications. Unlike PN, AN is often asymptomatic. Among symptomatic patients (55%), erectile dysfunction seems to be the sole symptom, in line with the higher degree of parasympathetic damage.     

Amyloid neuropathy mimicking chronic inflammatory demyelinating polyneuropathy

Introduction: Amyloid neuropathy is a rare peripheral neuropathy that classically presents as a progressive sensory neuropathy with prominent autonomic involvement. Methods: We describe 5 patients with amyloid neuropathy (familial amyloid polyneuropathy or acquired amyloidosis) who were initially mistaken to have chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) based on history, clinical examination, electrodiagnostic studies, and cerebrospinal fluid (CSF) analysis. Results: The diagnosis of CIDP had been retained on clinical and electrophysiological grounds for all patients, but we observed no improvement after immunomodulatory treatment. Nerve biopsy confirmed amyloid deposits in nerves, and molecular genetic analysis showed a mutation of the transthyretin (V30M) gene for 3 patients; the 2 other patients had acquired amyloidosis. Conclusions: This report emphasizes the need to look for an alternative diagnosis in CIDP patients who do not respond to treatment and to look carefully for symptoms or signs of autonomic involvement in such patients. Muscle Nerve 45: 26–31, 2012     

Better diagnostic accuracy of neuropathy in obesity: A new challenge for neurologists

Objective

To determine the comparative diagnostic characteristics of neuropathy measures in an obese population.

交感皮肤反应对糖尿病自主神经病变的诊断价值

目的探讨交感皮肤反应（sympathetic skin response,SSR）在糖尿病自主神经病变诊断中的价值。方法对186例糖尿病周围神经病（Diabetic peripheral neuropathy,DPN）患者和203例糖尿病非DPN患者进行SSR检测,同时对102例健康人进行SSR检测。结果SSR起始潜伏期异常率高于波幅异常率,下肢的异常率高于上肢异常率。DPN患者中,174例（93.5%）SSR异常,其中32例未引出SSR,142例起始潜伏期延长,109例波幅下降。203例DM非DPN患者中,46例（22.7%）SSR起始潜伏期延长和/或波幅下降,其中19例有出汗异常,4例在检查后数月出现出汗异常。结论SSR是早期诊断糖尿病自主神经病变的敏感手段,可发现亚临床神经病,并与病情进展相吻合。     

Helicobacter pylori infection and gastric function in primary autonomic neuropathy

Helicobacter pylori (Hp) infection in diabetic patients has been related to impaired gastric clearance of bacteria due to autonomic neuropathy. Gastrointestinal dysfunction has been described in primary autonomic failure (AF). The aim of the study was to evaluate, for the first time, the presence of Hp infection and gastric function in patients with primary AF. Twelve patients with primary AF (aged 58–78), 31 healthy controls (aged 48–75) and 31 patients affected by type 2 diabetes (aged 46–75) were studied. A ¹³C-urea breath test was performed to assess the presence of Hp infection. To evaluate gastric function, AF patients underwent two non-invasive tests: 1) ¹³C-octanoic acid breath test (OBT) to evaluate gastric emptying, and 2) electrogastrogram (EGG) to evaluate gastric electrical activity. Hp infection was found in 100 % of AF patients, in 48 % of controls and in 71 % of diabetic patients (p = 0.02 between groups). Electrical or mechanical gastric function was altered in 50 % of AF patients. In particular, 1) after OBT, half-time gastric emptying was delayed in 6 out of 12 patients, and 2) EGG showed the presence of gastric dysrhythmias in 6 out of 12 patients. In conclusion, Hp infection was detected in all AF patients studied; as previously demonstrated in diabetes, such a finding might be related to autonomic neuropathy causing mechanical or electrical gastric dysfunction. Hp detection might be important for the gastrointestinal and extradigestive complications of such infection. Received: 4 August 2001, Accepted: 11 March 2002