Thermal quantitative sensory testing as a screening tool for cardiac autonomic neuropathy in patients with diabetes mellitus.

INTRODUCTION: Electrophysiological diagnosis of cardiac autonomic neuropathy (CAN) is based on the evaluation of cardiovascular autonomic reflex tests (CARTs). CARTs are relatively time consuming and must be performed under standardized conditions. This study aimed to determine whether thermal quantitative sensory testing (TQST) can be used as a screening tool to identify patients with diabetes at a higher risk of CAN. METHODS: Eighty-five patients with diabetes and 49 healthy controls were included in the study. Neurological examination, CARTs, TQST, biochemical analyses, and neuropathy symptom questionnaires were performed. RESULTS: CAN was diagnosed in 46 patients with diabetes (54%). CAN-positive patients with diabetes had significantly higher warm detection thresholds (WDT) and significantly lower cold detection thresholds (CDT) in all tested regions (thenar, tibia, and the dorsum of the foot). CDT on the dorsum < 21.8°C in combination with CDT on the tibia < 23.15°C showed the best diagnostic ability in CAN prediction, with 97.4 % specificity, 60.9% sensitivity, 96.6% positive predictive value, and 67.3% negative predictive value. CONCLUSION: TQST can be used as a screening tool for CAN before CART.

Risk factors for depression and anxiety in painful and painless diabetic polyneuropathy: A multicentre observational cross-sectional study.

BACKGROUND: Despite the high prevalence of depression and anxiety in chronic pain conditions, current knowledge concerning emotional distress among painful diabetic polyneuropathy (pDSPN) and other diabetes mellitus (DM) sufferers is limited. METHODS: This observational multicentre cohort study employed the Hospital Anxiety and Depression Scale, the Beck Depression Inventory II and the State-Trait Anxiety Inventory to assess symptoms of depression and anxiety in several groups with diabetes, as well as in a control group. The study cohort included 347 pDSPN patients aged 63.4 years (median), 55.9% males; 311 pain-free diabetic polyneuropathy (nDSPN) patients aged 63.7 years, 57.9% males; 50 diabetes mellitus (DM) patients without polyneuropathy aged 61.5 years, 44.0% males; and 71 healthy controls (HC) aged 63.0 years, 42.3% males. The roles played in emotional distress were explored in terms of the biological, the clinical (diabetes-, neuropathy- and pain-related), the socio-economic and the cognitive factors (catastrophizing). RESULTS: The study disclosed a significantly higher prevalence of the symptoms of depression and anxiety not only in pDSPN (46.7% and 60.7%, respectively), but also in patients with nDSPN (24.4% and 44.4%) and DM without polyneuropathy (22.0% and 30.0%) compared with HCs (7.0% and 14.1%, p < 0.001). Multiple regression analysis demonstrated the severity of pain and neuropathy, catastrophic thinking, type 2 DM, lower age and female sex as independent contributors to depression and anxiety. CONCLUSIONS: In addition to the severity of neuropathic pain and its cognitive processing, the severity of diabetic polyneuropathy and demographic factors are key independent contributors to emotional distress in diabetic individuals. SIGNIFICANCE: In large cohorts of well-defined painless and painful diabetic polyneuropathy patients and diabetic subjects without polyneuropathy, we found a high prevalence of the symptoms of depression and anxiety, mainly in painful individuals. We have confirmed neuropathic pain, its severity and cognitive processing (pain catastrophizing) as dominant risk factors for depression and anxiety. Furthermore, some demographic factors (lower age, female sex), type 2 diabetes mellitus and severity of diabetic polyneuropathy were newly identified as important contributors to emotional distress independent of pain.

Antibodies to the Caspr1/contactin-1 complex in chronic inflammatory demyelinating polyradiculoneuropathy.

Previous studies have described the clinical, serological and pathological features of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and antibodies directed against the paranodal proteins neurofascin-155, contactin-1 (CNTN1), contactin-associated protein-1 (Caspr1), or nodal forms of neurofascin. Such antibodies are useful for diagnosis and potentially treatment selection. However, antibodies targeting Caspr1 only or the Caspr1/CNTN1 complex have been reported in few patients with CIDP. Moreover, it is unclear if these patients belong to the same pathophysiological subgroup. Using cell-based assays in routine clinical testing, we identified sera from patients with CIDP showing strong membrane reactivity when both CNTN1 and Caspr1 were co-transfected (but not when CNTN1 was transfected alone). Fifteen patients (10 male; aged between 40 and 75) with antibodies targeting Caspr1/CNTN1 co-transfected cells were enrolled for characterization. The prevalence of anti-Caspr1/CNTN1 antibodies was 1.9% (1/52) in the Sant Pau CIDP cohort, and 4.3% (1/23) in a German cohort of acute-onset CIDP. All patients fulfilled European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) definite diagnostic criteria for CIDP. Seven (47%) were initially diagnosed with Guillain-Barré syndrome due to an acute-subacute onset. Six (40%) patients had cranial nerve involvement, eight (53%) reported neuropathic pain and 12 (80%) ataxia. Axonal involvement and acute denervation were frequent in electrophysiological studies. Complete response to intravenous immunoglobulin was not observed, while most (90%) responded well to rituximab. Enzyme-linked immunosorbent assay (ELISA) and teased nerve fibre immunohistochemistry confirmed reactivity against the paranodal Caspr1/CNTN1 complex. Weaker reactivity against Caspr1 transfected alone was also detected in 10/15 (67%). Sera from 13 of these patients were available for testing by ELISA. All 13 samples reacted against Caspr1 by ELISA and this reactivity was enhanced when CNTN1 was added to the Caspr1 ELISA. IgG subclasses were also investigated by ELISA. IgG4 was the predominant subclass in 10 patients, while IgG3 was predominant in other three patients. In conclusion, patients with antibodies to the Caspr1/CNTN1 complex display similar serological and clinical features and constitute a single subgroup within the CIDP syndrome. These antibodies likely target Caspr1 primarily and are detected with Caspr1-only ELISA, but reactivity is optimal when CNTN1 is added to Caspr1 in cell-based assays and ELISA.

Cardiac autonomic neuropathy may play a role in pathogenesis of atherosclerosis in type 1 diabetes mellitus.

AIMS: Cardiac autonomic neuropathy (CAN) is a frequent and severe complication of type 1 diabetes mellitus (T1DM). CAN diagnosis is associated with increased cardiovascular morbidity and mortality, often due to progressive atherosclerosis. Carotid intima media thickness (CIMT) is a surrogate marker of the atherosclerosis. The aim of our study was to evaluate the relationship between CIMT and CAN in T1DM patients. METHODS: Total of 49 T1DM patients and 45 healthy controls were examined for CAN presence and CIMT. CAN was diagnosed based on the results of Ewing test battery and spectral analysis of heart rate variability. CIMT was measured by two-dimensional ultrasound. Biochemical, anthropometric and anamnestic risk markers of atherosclerosis were evaluated. We used logistic types of generalized additive models (GAM) for statistical analysis. RESULTS: CAN was detected in 22 out of 49 T1DM patients (45%). All 45 healthy controls had normal cardiovascular autonomic tests results. CIMT was significantly positively associated with T1DM diagnosis (p=0.0251), CAN diagnosis (p=0.007), age (p<0.0001), BMI (p=0.0435) and systolic blood pressure (p=0.0098). CAN effect on CIMT interacted with the effect of T1DM. The combination of both factors significantly increased CIMT more than the sum of the individual T1DM and CAN status. CONCLUSIONS: CAN is significantly associated with higher CIMT in T1DM patients. CAN may play a role in pathogenesis of atherosclerosis in type 1 diabetes mellitus.