Polyneuropathy Patients Research Articles

High Plasma Pentraxin 3 Levels in Diabetic Polyneuropathy Patients with Nociceptive Pain.

Diabetic polyneuropathy is the most common neurologic complication of diabetes mellitus. Underlying mechanisms of diabetic polyneuropathy are related to various metabolic and inflammatory pathways. Pentraxin 3 (PTX3) is an acute phase protein that is produced locally at the inflammatory sites by several cell types. Thioredoxin binding protein 2 (TBP2) is a thioredoxin regulator involved in intracellular energy pathways and cell growth. We measured the plasma levels of PTX3 and TBP2 in type 2 diabetic patients (n = 27) with pain complaints and compared their levels with those of healthy age- and sex-matched subjects (n = 24). Moreover, the diabetic patients were divided into two groups using the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain scale: patients with nociceptive pain that is caused by tissue damage and patients with neuropathic pain that is caused by nerve damage. Patients with LANSS scores of < 12 were considered to have nocicceptive pain (n = 15), while patients with LANSS scores of ≥ 12 were considered to have neuropathic pain (n = 12). We found that PTX3 levels were significantly higher in diabetic patients compared to controls (p = 0.03), but there was no significant difference in the TBP2 levels. Importantly, patients with nociceptive pain had significantly higher PTX3 levels compared to patients with neuropathic pain (p < 0.05). Thus, plasma PTX3 levels can be helpful for discrimination of nociceptive pain from neuropathic pain in diabetic patients. We propose that PTX3 may contribute to the onset of nociceptive pain.

Autoantibodies to tetraspanins (CD9, CD81 and CD82) in demyelinating diseases

Tetraspanin family proteins, CD9, CD81 and CD82 are expressed in the oligodendrocytes and Schwann cells. We investigated autoantibodies to tetraspanin proteins in patients with demyelinating diseases. Sera were collected from 119 multiple sclerosis patients, 19 neuromyelitis optica, 42 acute inflammatory demyelinating polyneuropathy, 23 chronic inflammatory demyelinating polyneuropathy and 13 acute motor axonal neuropathy as well as 55 healthy controls. Few multiple sclerosis and acute inflammatory demyelinating polyneuropathy patients had autoantibodies that were weakly reactive to CD9 or CD81 but the significance is unclear. It is unlikely that these autoantibodies are pathogenic or serve as potential biomarkers in demyelinating diseases.

Construction and validation of the chronic acquired polyneuropathy patient‐reported index (CAP‐PRI): A disease‐specific, health‐related quality‐of‐life instrument

Generic health-related quality-of-life (HRQOL) patient-reported outcome measures have been used in patients with chronic immune-mediated polyneuropathies. We have created a disease-specific HRQOL instrument. The chronic acquired polyneuropathy patient-reported index (CAP-PRI) was developed and validated in multiple steps. Items were initially generated through patient and specialist input. The performance of the preliminary 20 items was analyzed via a prospective, 5-center study involving chronic immune-mediated polyneuropathy patients. Data analysis suggested modification to a 15-item scale with 3 response categories rather than 5. The final CAP-PRI was validated in another prospective, 5-center study. The CAP-PRI appeared to be a unidimensional outcome measure that fit the Rasch model in our multicenter cohort. It correlated appropriately with outcome measures commonly used in this patient population. The CAP-PRI is a simple disease-specific HRQOL measure that appears to be useful for clinical care and possibly also for clinical trials. Muscle Nerve 54: 9-17, 2016.

Distal Symmetric Polyneuropathy: A Review.

Peripheral neuropathy is a highly prevalent and morbid condition affecting 2% to 7% of the population. Patients frequently experience pain and are at risk of falls, ulcerations, and amputations. We aimed to review recent diagnostic and therapeutic advances in distal symmetric polyneuropathy, the most common subtype of peripheral neuropathy. Current evidence supports limited routine laboratory testing in patients with distal symmetric polyneuropathy. Patients without a known cause should undergo a complete blood cell count, comprehensive metabolic panel, vitamin B12 measurement, serum protein electrophoresis with immunofixation, fasting glucose measurement, and glucose tolerance test. The presence of atypical features such as asymmetry, non-length dependence, motor predominance, acute or subacute onset, and prominent autonomic involvement should prompt a consultation with a neurologist or neuromuscular specialist. Electrodiagnostic tests and magnetic resonance imaging of the neuroaxis contribute substantial cost to the diagnostic evaluation, but evidence supporting their use is lacking. Strong evidence supports the use of tricyclic antidepressants, serotonin norepinephrine reuptake inhibitors, and voltage-gated calcium channel ligands in the treatment of neuropathic pain. More intensive glucose control substantially reduces the incidence of distal symmetric polyneuropathy in patients with type 1 diabetes but not in those with type 2 diabetes. The opportunity exists to improve guideline-concordant testing in patients with distal symmetric polyneuropathy. Moreover, the role of electrodiagnostic tests needs to be further defined, and interventions to reduce magnetic resonance imaging use in this population are needed. Even though several efficacious medications exist for neuropathic pain treatment, pain is still underrecognized and undertreated. New disease-modifying medications are needed to prevent and treat peripheral neuropathy, particularly in type 2 diabetes.

Acutely deteriorated extravascular volume overload during peripheral blood stem cell mobilization in POEMS syndrome: A case series with cytokine analysis

We describe two cases of polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS) syndrome patients with deteriorated extravascular volume overload without increased levels of vascular endothelial growth factor after the administration of cyclophosphamide + granulocyte colony-stimulating factor for stem cell mobilization. We then measured the serum levels of 27 cytokines from these cases using a multiplex suspension array system. The analysis revealed the changes of cytokine profiles before cyclophosphamide + granulocyte colony-stimulating factor and after the development of capillary leak symptoms in both cases. This may improve our current level of understanding of the pathogenesis of POEMS syndrome not driven by vascular endothelial growth factor.

Monitoring safety and effectiveness of Tafamidis in transthyretin amyloidosis in Italy: a 3-year longitudinal multicenter study in a non-endemic area

Background Tafamidis is a transthyretin (TTR) stabilizer able to prevent mutated TTR tetramer dissociation into amyloidogenic monomers. There have been a few encouraging studies on safety and long-term efficacy of Tafamidis in early-onset Val30Met TTR-familial amyloid polyneuropathy (TTR-FAP) patients. However, less is known about its efficacy in later stages of the disease and in non-Val30Met mutations.

Long-term Results of Domino Liver Transplantation for Hepatocellular Carcinoma Using the "Double Piggy-back" Technique: A 13-Year Experience.

The aim of this study was to evaluate the long-term outcome of liver transplantation (LT) for hepatocellular carcinoma (HCC) with Domino LT (DLT) using the "Double Piggy-back" technique. DLT using livers from familial amyloidotic polyneuropathy (FAP) patients is a well-described technique and useful for expanding the donor pool. However, data on long-term results for HCC are limited, particularly regarding the use of the "Double Piggy-back" technique. Between 2001 and 2014, a total of 260 patients undergoing LT for HCC were analyzed from a prospective database. Of those, 114 were submitted to DLT. Comparisons between groups were performed using propensity score matching. Median follow-up was 34 months (1-152). Overall and disease-free 5-year survival rates for the whole population were 58% and 56%, respectively. There were 177 (68%) patients within Milan Criteria and an additional 26 (10%) within University of California San Francisco (UCSF) criteria. Patients older than 50 years were more likely to receive an FAP liver [odds ratio (OR) 1.94, confidence interval (CI) 1.02-3.69]. DLT patients had more major complications (23.7% vs 13.0%, P = 0.025). Only patients undergoing DLT presented with piggy-back syndrome (7% vs 0%, P = 0.001). After adjusting for potential confounders, DLT and cadaveric LT had a similar 5-year survival rate (59% vs 44%, respectively, P = 0.117). Thirteen patients (11.4%) evidenced FAP disease but not before 6 years after DLT. DLT for HCC is feasible and achieves equivalent results to cadaveric LT. The benefit of expanding the donor pool must be balanced against higher morbidity and a real risk of disease transmission.

A neurophysiological study of large- and small-diameter nerve fibers in the hands of hemodialysis patients

Polyneuropathy in patients with advanced clinical kidney disease is a very disabling condition. The aim of this study was to evaluate neurophysiological abnormalities of large- and small-diameter nerve fibers in the hands of hemodialysis patients. A total of 38 hemodialysis patients and 38 healthy control subjects underwent a conventional electrophysiological examination. The function of small nerve fibers was assessed using cutaneous silent period (CSP) measurement. Slower median nerve motor conduction velocities were recorded in patients with fistula (p < 0.0001) and without fistula (p < 0.001). Sensory median and ulnar nerve conduction velocities were slower in both patient groups compared with the control group (p = 0.001). Median sensory nerve action potential amplitudes were lower in patients with fistulas (p = 0.009) and without fistulas (p = 0.005) compared with the control group. Significantly prolonged F-wave latencies of the median (p = 0.002) and ulnar nerves (p = 0.023) in patients with fistulas hands were observed. In 12/38 (32 %) patients, the onset latencies of CSPs were significantly delayed (p = 0.001). There was an inverse correlation of β2-microglobulin and decreased conduction velocities of the median nerves, while Kt/V was associated with improved sensory nerve conduction velocity of the median nerve. An inverse correlation between motor velocity of both nerves and hemodialysis duration was observed in the patient groups. The measurement of CSPs provides a useful method for assessing small nerve fibers. The role of A-delta fibers is often overlooked.

Causes of сritical illness polyneuropathy in adults after cardiac surgery

Background: Critical illness polyneuropathy (CIP) is the most common complication of peripheral nervous system after cardiac surgery. Тhe aim of the research was to determine the cause of critical illness polyneuropathy in the patients who had operations on the heart. Material and methods: The study included 55 patients (32 men, 23 women) who underwent of surgery on the heart with cardiopulmonary bypass. Patients underwent coronary artery bypass grafting in 52.7% of cases; reconstructive surgery on the heart valves in 47.3% of cases. Patients had characteristics comparable age and sex. All patients used Sevaran as anesthesia. All patients were assessed preoperative, intraoperative and postoperative characteristics. Stimulation EMG was performed before the operation and on the 7th day after surgery. Estimated amplitude of the M-response to the speed of motor and sensory fibers, F-wave. Results: 15 patients (7 - men, 8 - women) after heart surgery debuted сritical illness polyneuropathy confirmed by EMG. Patients with signs of polyneuropathy in the postoperative period in 100% of cases had multiple organ failure syndrome and systemic inflammatory response, (p < 0,01). These patients were longer in the intensive care unit, (p < 0,05), longer they were held ventilation, more often required inotropic support, (p < 0,05) and more likely to suffer pneumonia, (p < 0,05). Conclusions: Critical illness polyneuropathy can develop in patients that have undergone heart surgery with cardiac bypass as the result of multiple organ injury syndrome and systemic inflammation response syndrome. Comorbidity background, types of heart surgery, the technique of surgical intervention, especially of anesthetic, duration of respiratory care, inotropic support and sedation are not the cause of critical illness polyneuropathy in patients undergoing heart surgery.

Elevated level of creatinine phosphokinase in the blood of patients with peripheral polyneuropathies

Creatinine phosphokinase (CPK) elevated levels in blood are distinguished marker of neuromuscular diseases, especially myopathies, but can be found in great number of diseases as in hearth and brain tissue damages, some endocrine disturbances, malignant diseases, toxic and unwanted effects, febrile states, excessive motor activity. In inherited polyneuropathies, CPK levels are within normal values. Recently, hereditary peripheral sensomotor axonal, autosomal recessive polyneuropathy, associated with neuromyotonia (HINT1 polyneuropathy) has been recognized. Frequency and levels of hyper-CPK determination in HINT1 polyneuropatahy were examined in 31 patients (11 male/20 female), with HINT1 polyneuropathy and founder R37P mutation in HINT1gene. Elevated CPK levels (183–1170 IU/L) were found in HINT1 polyneuropathy patients. Levels >500 IU/L were found in generalized myothonia patients. Elevated CPK blood levels may be a direct consequence of electrophysiologically confirmed generalized neuromyotonia. Electromyography with nerve conduction study is very important for recognition of axonal polyneuropathy with neuromyotonia, in differential diagnosis of myotonic dystrophy and other myotonic disorders.

Low vitamin D levels in healthy controls and patients with autoimmune neuromuscular disorders in Greece

Normal autoimmune function is dependent on adequate levels of activated vitamin D, 25 hydroxy vitamin D [25(OH)D]. A recent study presented deficiency of 25(OH)D levels in Swedish MG patients. We aimed to study 25(OH)D levels in patients with MG and autoimmune polyneuropathies (PNP) at a southern latitude in Greece. Plasma levels of 25(OH)D were analyzed in Greek patients with MG (n = 19), immune-mediated PNP (N = 11) and in 30 Greek healthy age- and sex-matched controls. Ten MG patients received supplementation with vitamin D3. The MG Composite Score (MGC) and MG quality of life assessed disease severity in MG patients, whereas the INCAT Disability Scale assessed clinical features in the PNP patients. MG patients with and without vitamin D3 supplementation had higher 25(OH)D levels (mean 58.8 ± 16.3 and 62.0 ± 22.4 nmol/L, respectively) than PNP patients (mean 42.1 ± 11.5 nmol/L, p = 0.01) and healthy controls (mean 45.7 ± 13.8 nmol/L, p = 0.01). Plasma 25(OH)D levels was lower with age in all groups. There were no correlations between 25(OH)D and disease duration, MGC score, or INCAT score. Vitamin D deficiency was found in all Greek patient groups and healthy controls. Levels of 25(OH)D were higher in MG patients with as well as without vitamin D supplementation compared to healthy controls, whereas CIDP/GBS patients had levels similar to controls.

Evaluation of violation vibration sensitivity for early diagnosis of diabetic distal polyneuropathy in patients with type 1 diabetes in the Republic of Belarus

Evaluation of violation vibration sensitivity for early diagnosis of diabetic distal polyneuropathy in patients with type 1 diabetes in the Republic of Belarus

Contactin 1 IgG4 associates to chronic inflammatory demyelinating polyneuropathy with sensory ataxia.

A Spanish group recently reported that four patients with chronic inflammatory demyelinating polyneuropathy carrying IgG4 autoantibodies against contactin 1 showed aggressive symptom onset and poor response to intravenous immunoglobulin. We aimed to describe the clinical and serological features of Japanese chronic inflammatory demyelinating polyneuropathy patients displaying the anti-contactin 1 antibodies. Thirteen of 533 (2.4%) patients with chronic inflammatory demyelinating polyneuropathy had anti-contactin 1 IgG4 whereas neither patients from disease or normal control subjects did (P = 0.02). Three of 13 (23%) patients showed subacute symptom onset, but all of the patients presented with sensory ataxia. Six of 10 (60%) anti-contactin 1 antibody-positive patients had poor response to intravenous immunoglobulin, whereas 8 of 11 (73%) antibody-positive patients had good response to corticosteroids. Anti-contactin 1 IgG4 antibodies are a possible biomarker to guide treatment option.

Life paths of familial amiloidotic polyneuropathy patients: a descriptive study

Methods A common social demographic questionnaire and a questionnaire about family history/personal disease and biographic events were applied to 211 subjects (in 110, the disease had already begun, 82 were asymptomatic carriers, and 19 had no established diagnosis), attending external consultation at Corino de Andrade Unit in Centro Hospitalar do Porto. A descriptive analysis and frequencies were obtained.

Psychopathological dimensions in familial amyloid polyneuropathy patients

There are very few studies about psychopathology in familial amyloid polyneuropathy patients or in asymptomatic carriers. In our clinical experience in a psychiatric and psychological consultation, we mostly see patients suffering from depression and anxiety symptoms and emotional distress related to some specific, emotionally charged moments caused by the disease. We wanted to evaluate psychopathological dimensions in the population that attends external consultation at Corino de Andrade Unit.

Etiological patterns of polyneuropathy in a tertiary level hospital of Bangladesh

The causes of polyneuropathy are many and it is important to identify them, as some of them, especially the inflammatory types are treatable. To explore the different etiological factors of polyneuropathy, this cross sectional study was carried out in the department of Neurology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbag, Dhaka. Data were collected by taking medical history and clinical examination and subsequent laboratory investigations. A total of 60 subjects were included in this study and mean age of the entire patient was 42.25 year. Out of all respondents, 83.3% had muscle weakness, similar number had problems with object handling, 66.3% had muscle cramp, 63.3% had impaired standing or gait, 55.0% had distal paraesthesia, 41.7% had burning feet, 8.3% had restless legs and 5.0% had stiffness. Out of all patients of polyneuropathy, 33.3% had diabetic neuropathy, 11.7% had Guillain-Barré syndrome, 10.0% had chronic inflammatory demyelinating polyneuropathy, similar number had unknown etiology, 6.7% had charcot-marry-tooth disease disease, 6.7% had renal failure, 5.0% had leprosy, Vitamin B 12 deficiency and chronic liver disease of each, 3.3% had history of isoniazide drug intake and similar had systemic lupus erythromatosus. We conclude that, polyneuropathy has wide variety of etiological factors. Among them, diabetes is the most common factor. Further large controlled study is needed to establish the etiological pattern in the context of Bangladesh. DOI: http://dx.doi.org/10.3329/bmj.v43i1.21371 Bangladesh Med J. 2014 January; 43 (1): 17-20

Efficiency of long-term treatment with intravenous immunoglobulins correlates with reduced autoreactive T cell responses in chronic inflammatory demyelinating polyneuropathy patients.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare disease of the peripheral nervous system, characterized by gradual increasing weakness of the limbs, with more than 50% of patients experiencing marked disability 1. The underlying pathophysiological mechanism of CIDP remains unknown; however, studies have shown activated T cells in the circulation of CIDP patients 2–4. In addition, patient studies suggest a key role for autoreactive T cell responses against peripheral myelin antigens such as P0, P1, P2 and peripheral myelin protein PMP-22 5,6. Mechanism-of-action studies in other chronic autoimmune diseases have shown that the T cell memory compartment influences antigen responses by showing up-regulation of CD4+ or CD8+ T effector memory (TEM) cells 7,8. Recently, published data from a randomized, placebo-controlled clinical trial demonstrated the long-term efficacy and safety of intravenous immunoglobulin (IVIg) treatment in CIDP patients 9. However, the underlying mechanism of action of IVIg in the treatment of CIDP remains unclear 10,11. The aim of this study was to investigate the course of autoreactive T cell responses against the two peripheral myelin antigens P2 and PMP-22 in addition to the frequency of memory T cell subsets during IVIg treatment in CIDP patients 12.

Health, Social and Economic Consequences of Polyneuropathy: A Controlled National Study Evaluating Societal Effects on Patients and Their Partners

Objectives: To estimate the direct and indirect factual costs of polyneuropathy in a national sample of patients and their spouses based on a national register-based cohort study with matched controls. Methods: Using records from the Danish National Patient Registry (1997-2009) all patients with a diagnosis of polyneuropathy and their partners were identified and compared with randomly chosen controls matched for age, gender, geographic area and civil status. Direct costs included frequencies of primary and secondary sector contacts and procedures, and medication. Indirect costs included the effect on labor supply. Social-transfer payments were included to illustrate the effect on national accounts. All cost data were extracted from national databases. Results: 13,758 unspecified polyneuropathy patients were registered. They were compared with 54,900 matched controls identified from the National Danish Patient Registry. In addition, partners of patients in the case group were matched with partners in the corresponding control group. Almost half of the patients in the patient group had a partner. Patients had significantly higher rates of health-related contacts, medication use and greater socioeconomic costs than controls. They had very marginally lower employment rates, and those who were employed generally had lower incomes. The sum of direct net healthcare costs after the injury (general practitioner services, hospital services and medication) and indirect costs (loss of labor market income) was €12,647 for patients and €2,984 for their partners over and above that of controls. Social-transfer payments were all significantly larger in patients than in control subjects. Furthermore, the patients already exhibited a negative social- and health-related status up to eleven years before the first diagnosis, particularly for those with the highest costs. The health effects were present in all age groups and in both genders. Conclusions: Patients with a diagnosis of polyneuropathy experience increased mortality, morbidity and socioeconomic consequences. i 2014 S. Karger AG, Basel

Outflow reconstruction with arterial patch in domino liver transplantation: a new technical option

Domino liver transplantation (LT), using livers from familial amyloidotic polyneuropathy (FAP) patients, is a well described technique useful to expand donor pool. One of the main difficulties of this type of LT arises from the necessity to share the vascular pedicles between the graft and the donor. The most important challenge resides in restoring a proper hepatic venous outflow in the FAP-liver recipient. This is specially challenging when using the piggy-back technique, because the hepatic stumps may be too short. To overcome this issue, surgeons explored several techniques using different types of venous grafts. We describe a new technical option by using an arterial graft from the deceased donor. By using both iliac arteries a long graft is created and sutured as needed to the hepatic vein stump. We describe herein this new technique employed in a domino liver recipient who underwent retransplantation for ischemic cholangitis. The procedure was performed using the piggy-back technique; the venous stump of the FAP liver was reconstructed with the arterial graft. The patient had uneventful postoperative and mid-term hepatic function, and anastomosis was patent 24 months after LT.

Clinical and electrophysiological characteristics of symmetric polyneuropathy in a cohort of systemic lupus erythematosus patients.

Peripheral neuropathy in systemic lupus erythematosus (SLE) is heterogeneous and its commonest pattern is symmetrical polyneuropathy. The aim of this study was to describe the prevalence, clinical and electrophysiological features, disease associations and effects on function and quality of life of polyneuropathy in SLE patients, defined using combined clinical and electrophysiological diagnostic criteria. Consecutive SLE patients seen at the University of Malaya Medical Centre were included. Patients with medication and other disorders known to cause neuropathy were excluded. Demographic, clinical and laboratory data were obtained using a pre-defined questionnaire. Function and health-related quality of life was assessed using the modified Rankin scale and the SF-36 scores. Nerve conduction studies (NCS) were carried out in both upper and lower limbs. Polyneuropathy was defined as the presence of bilateral clinical symptoms and/or signs and bilateral abnormal NCS parameters. Of 150 patients, 23 (15.3%) had polyneuropathy. SLE-related polyneuropathy was mainly characterized by sensory symptoms of numbness/tingling and pain with mild signs of absent ankle reflexes and reduced pain sensation. Function was minimally affected and there were no differences in quality of life scores. NCS abnormalities suggested mild length-dependent axonal neuropathy, primarily in the distal lower limbs. Compared to those without polyneuropathy, SLE-related polyneuropathy patients were significantly older but had no other significant demographic or disease associations. SLE-related polyneuropathy is a chronic, axonal and predominantly sensory neuropathy, associated with older age. Its underlying pathogenetic mechanisms are unknown, although a possibility could be an increased susceptibility of peripheral nerves in SLE patients to effects of aging.