Peripheral Polyneuropathy Research Articles

P 26: Metabolic effects of simvastatin and Omega-3 polyunsaturated fatty acids in type 2 diabetic patients with cardiovascular autonomic neuropathy

Diabetic neuropathies, including cardiovascular autonomic neuropathy (CAN), are a common chronic complications of Type 2 diabetes mellitus and confer high morbidity and mortality to diabetic patients. The present study has examined the metabolic effects of simvastatin (SIM), omega-3 polyunsaturated fatty acids (ω-3 PUFA) and their combinations in Type 2 diabetic patients with CAN. 76 Type 2 diabetic patients with CAN (54,7±3,6 years), BMI 27,8±2,3 kg/m2, HbA1c 7,1±0,7 % and 15 age-matched controls were observed. Fasting blood glucose, HbA1c, lipid profile, immunoreactive insulin (IRI), C-peptide, N-terminal pro B-type natriuretic peptide (NT-proBNP), leptin, tumor necrosis factor-α (TNF-α), high sensitivity C-rective protein (hs-CRP), interleukin-8 (IL-8), interleukin-18 (IL-18) were evaluated. HOMA-IR and HOMA-β-CF indexes were calculated. Heart rate variability (HRV) properties were assessed by Holter ECG. Patients with CAN were allocated to four groups: group A (n=15) received standart basic therapy; B (n=22) - SIM 20 mg; C (n=21) - capsules of fish oil [1,0 g (≈85% ω-3 PUFA)]; D (n=18) - SIM 10 mg plus capsules of fish oil. All patients were on the same diet. The duration of the study was 3 months. Statistics: ANOVA (MicroCal Origin v. 8,2)]. Lipid disorders [high level of total cholesterol, low density lipoprotein-cholesterol (LDL-C), triglycerides (TG) (P<0,05) and decreased level of high density lipoprotein-cholesterol (HDL-C)] in patients with CAN are accompanied by the increase of IRI, C-peptide, leptin, hs-CRP, IL-8, IL-18, NT-proBNP, TNF-α concentration in blood, increase of HOMA–IR and decrease of HOMA-β-CF parameters; correlation between leptin, TG concentration and parameters of insulin resistance were found. HRV properties are characterized by reduction of sympathetic, parasympathetic and humoral links tonus with predominance of sympathetic link of vegetative nervous system. After 3 months of treatment there was a more significant decrease in LDL-C (−42,9±2,25 %, p<0,001), TG (−44,1±3,15 %, p<0,001), increase of HDL-C (+15,8±1,35 %, p<0,001) concentration, positively influence on HRV, blood pressure in the 4-rd group. In particular, the decrease of IRI (−21,1±2,04 %, p<0,001), HOMA–IR (−25,3±3,18 %, p<0,001), leptin (−19,4±1,9 %, p<0,001), C-peptide (−16,2±2,25 %, p<0,01), hs-CRP (−18,3±2,04 %,p<0,001), IL-8 (−11,1±2,45 %, p<0,05), IL-18 (−10,0±1,74 %, p<0,05), NT-proBNP(−9,7±2,12%, p<0,05), TNF-α (−16,4±2,27%, p<0,001), increase of root mean square successive difference, HOMA-β-CF parameters (P<0,05) were observed. Usage of ω-3 PUFA in treatment of Type 2 diabetic patients with CAN improve the general condition of patients, contribute to clinical disease symptoms regression. By the evaluation of vegetative state the total score was significantly decreased (p<0,01). In addition, in most patients with CAN and peripheral polyneuropathy reduction of pain, paresthesias, frequency of muscles courts, improvement of tactile, vibration and temperature sensitivity, pulse flow performance and capillaroscopy was observed. Positive impact of the combined administration of SIM and ω-3 PUFA on the lipid profile, concentration of IRI, hs-CRP, NT-proBNP, some adipokins in blood and reported before mild hypotensive and vegetomodulation effects allows to recommend their combination in the complex treatment of Type 2 diabetic patients with CAN.

CIDP PRESENTING WITH RADICULOPATHY

A 62-year-old gentleman presented in 2009 with pain, numbness and tingling in the right hand and arm. Neurological examination revealed reduced light touch and pain sensation in the C8 dermatome....

The prevalence of neurological disorders in older people in Tanzania

There are few data on neurological disorders prevalence from low- and middle-income countries, particularly sub-Saharan Africa (SSA) and none specific to the African elderly. We aimed to determined the prevalence of neurological disorders in those aged 70 years and over in a rural African community. This study was a cross-sectional two-phased community epidemiological survey set in the rural Hai district of Tanzania. Screening was performed with a validated screening questionnaire with high sensitivity and specificity. Positive responders to screening underwent full neurological history and examination to confirm or refute the presence of neurological disorders and to classify the disorder using the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10). Of 2232 participants, there were 384 neurological diagnoses amongst 349 people. The age-adjusted prevalence of people with neurological diagnoses was 154.1 per 1000 (95% CI 139.2-169.1). The age-adjusted prevalence per 1000 of the most common neurological disorders were tremor (48.2), headache (41.8), stroke (23.0), peripheral polyneuropathy (18.6), upper limb mononeuropathy (6.5) and parkinsonism (5.9). This is the first published community-based neurological disorders prevalence study specifically in the elderly in SSA. It reveals a high prevalence of neurological morbidity and demonstrates the contribution neurological disorders make to the non-communicable disease epidemic. This is likely to increase as the population of low-income countries ages constituting a public health dilemma.

Skleromyxödem

Scleromyxedema is a rare connective tissue disease that may affect numerous internal organs in addition to the skin. The disease is almost exclusively associated with monoclonal gammopathy. This retrospective study summarizes the clinical characteristics of four patients with scleromyxedema. In all of the patients a systematic serological and apparative check-up was performed. The mean age of the four patients (three women and one man) was 51 years. In all cases, monoclonal gammopathy (3 cases of IgG lambda and 1 case of IgG kappa) was involved. In one patient, skin lesions were restricted to the upper part of the body and three patients had generalized disease. The internal organs of all patients were affected with fibrosis of the lungs, myositis and arthritis, peripheral polyneuropathy and hypomotility of the esophagus. The most effective forms of treatment in this patient collective were dexamethasone-pulse therapy, intravenous immunoglobulins and bortezomib. All patients had recurrences after finishing therapy. The mean observation period after the initial diagnosis of scleromyxedena was 6.25 years (range 2-11 years). Scleromyxedema is a rare multisystemic disease. The heterogeneous affection of internal organs necessitates a comprehensive check-up. The response to recently published treatment strategies is low and recurrences after finishing therapy are frequent.

Treatment of scleromyxedema with IVIg

Results An 18 year old male presented with a rash of three weeks duration. Soon after the rash appeared, he developed pain and swelling of the right hand, as well as numbness and tingling of the right forearm. A recreational weight lifter, he noticed progressively decreasing stamina and amount of weight that he could lift. Swelling of the eyelids and bridge of nose prompted treatment for an allergic reaction, but these signs did not improve with antihistamines and oral corticosteroids. Family history was significant for the patient’s father and paternal grandfather both having a history of Idiopathic Thrombocytopenic Purpura. Physical exam revealed 2-3 mm skin-colored papules scattered on arms and thorax, with prominent areas at the base of neck and shoulders. Periorbital and glabellar swelling were visible, and bogginess of the left 3rd metacarpalphalengeal joint was present. Strength was decreased in arms and legs, 3/5 and 4/5 respectively. Sensation for pin-prick and vibration was decreased in a stocking/glove distribution of the distal extremities. He had a fine tremor of the tongue and right arm. A shaved skin biopsy showed a papule with prominent mucin deposition (alcian blue staining) and increased fibroblast cellularity. Bone marrow aspirate showed mild hypocellularity with 2-3% plasma cells (polyclonal). Serum IgE level was 884 IU/mL, however serum protein electrophoresis and immunoelectrophoresis were normal. Electromyography (EMG) was consistent with a sensory/motor peripheral polyneuropathy with demyelinating and axonal features involving the arms. Additional laboratory workup for underlying autoimmune, thyroid, neurologic, infectious and neoplastic disease was negative. Based on histopathology and clinical features, he was diagnosed with Scleromyxedema, and therapy with intravenous immunoglobulin (IVIg) was initiated with moderate symptomatic improvement after the first infusion. After three infusions, there was complete resolution of symptoms, and he had a normal physical exam without rash or neurologic abnormalities. He was treated with IVIg for a

Chronic immune‐mediated axonal polyneuropathy following umbilical cord blood transplant for childhood‐onset cerebral adrenoleukodystrophy

Peripheral polyneuropathy is an unusual complication after organ transplantation and HSCT. The present study describes the case of an eight-yr-old boy diagnosed with ALD who underwent HLA-matched UCBT under a reduced-intensity conditioning regimen and developed progressive walking difficulty and hand clumsiness 11 months after transplantation. These symptoms were associated with cGVHD, identified as immune-mediated axonopathy by electrophysiological examination and sural nerve biopsy. Peripheral polyneuropathy should be kept in mind as a complication of GVHD.

Plasma homocysteine levels are independently associated with the severity of peripheral polyneuropathy in type 2 diabetic subjects

Peripheral polyneuropathy (PN) is a frequent complication of diabetes. However, mechanisms underlying the development of PN are multifactorial and not well understood. Our aim was to examine the association of plasma homocysteine (Hcy) with the prevalence and grade of peripheral PN in patients with type 2 diabetes (T2DM). We studied a cohort of 196 subjects with T2DM classified according to the grade of PN (Neuropathy Disability Score, NDS). Subjects with the highest grade of PN were older and had significantly increased levels of creatinine, microalbuminuria, HbA1c, and plasma Hcy compared to the other two groups. The differences in plasma Hcy values were maintained after correcting for confounding factors. Plasma Hcy, HbA1c, duration of diabetes, and age were predictors of the grade of PN. In conclusion, for each increase of 1 µmol in plasma Hcy there was a 23% increase of the risk of diabetic PN evaluated by NDS. Moreover, the grade of PN was predicted by plasma Hcy and HbA1c values, age and duration of diabetes. Further prospective studies should be conducted to confirm the association of plasma Hcy levels with the grade of PN in subjects with T2DM.

Efficacy and safety of lenalidomide and dexamethasone in overtreated multiple myeloma patients.

e18566 Background: Lenalidomide is a therapeutic option for pretreated patients with multiple myeloma, especially in association with steroids. Methods: Oraldaily lenalidomide (10-25 mg) for 21 days every month (median courses 8.6) and weekly dexamethasone (Dex) were administered until progression in 33 pretreated patients (median age 68.1 yrs) observed between June 2008 and January 2012 at Hematology Department of Sant’Andrea Hospital in Rome. Previous treatment included alkylants, anthracyclines, IFN-α, thalidomide, bortezomib and single or double autograft. Fifteen patients were evaluated after 6 courses of therapy, administered as second to fifth line, and prospectively followed-up; two patients weren’t considered because of early death. Treatment response was assessed according to IMWG uniform response criteria. Results: The overall response rate was 53.3% (8/15 pts) with a median duration of response of 12 months: 8 patients reached a partial response (PR), 6 showed a stable disease (SD) and 1 progressive disease (PD). The median progression free survival was 14 months. Among patients in PR, 5 are alive in continous treatment, 2 died due to PD after 17 courses administered as fifth line therapy and 1 died for unrelated surgical complicancies. The whole responses were achieved indifferently if lenalidomide was administered as second, third or fifth line of therapy (2, 3 and 3 patients respectively). Out of patients in SD, all experienced progressive disease after a median of 12 courses: 3 are still alive in salvage therapy, 3 died during treatment. The only patient in PD died 9 months after the end of Len-Dex treatment during salvage chemotherapy. The reported side effects included pneumonia, neutropenia, diarrhea, peripheral sensitive polyneuropathy, transient liver failure, lower urinary tract infection, skin rash, transient aphasia, conjunctival hemorrhage and deep vein thrombosis, all resolved with brief discontinuance and specific support therapy without hospitalization. Conclusions: Len-Dex association is a completely oral effective salvage therapy with good response rate and manageable side effects also for overtreated relapsed and refractory multiple myeloma patients.

Characterization of cerebrospinal fluid aminoterminally truncated and oxidized amyloid‐β peptides

Carboxyterminally elongated and aminoterminally truncated Aβ peptides as well as their pyroglutamate and oxidized derivates are major constituents of human amyloid plaques. The objective of the present study was to characterize aminoterminally truncated or oxidized Aβ38, Aβ40, and Aβ42 peptide species in immunoprecipitated human cerebrospinal fluid (CSF). We invented a novel sequential aminoterminally and carboxyterminally specific immunoprecipitation protocol and used the Aβ-SDS-PAGE/immunoblot for subsequent analysis of CSF Aβ peptide patterns. In the present study, we identified the aminoterminally truncated Aβ peptides 2-40 and 2-42 as well as oxidized forms of Aβ1-38 and Aβ1-42 in CSF. Our protocol allowed the quantification of a pattern of Aβ peptides 1-38(ox), 2-40, and 2-42 in addition to the well known panel of Aβ 1-37, 1-38, 1-39, 1-40, 1-40(ox), and 1-42 in a group of seven patients with peripheral polyneuropathy. In the present approach, we could broaden the range of quantifiable Aβ peptides described in previous studies (i.e., 1-37, 1-38, 1-39, 1-40, 1-40(ox), and 1-42) by Aβ 1-38(ox), 2-40, and 2-42. An exact analysis of CSF Aβ peptides regarding their carboxy- and aminoterminus as well as posttranslational modification seems promising with respect to diagnostic and pathogenic aspects.

High-tone electric muscles stimulation of thigh augments the impaired penile blood flow of diabetic patients without improving symptoms of erectile dysfunction

Erectile dysfunction (ED) is a major complication in diabetes mellitus. A novel method, high-tone external muscle stimulation (HTEMS), has been proven to be useful in the therapy of diabetic and uremic peripheral polyneuropathy. The aim of this study was to test the potential effect of HTEMS on ED in diabetic patients. An open-label, self-controlled interventional prospective study was conducted at the 2nd Department of Internal Medicine and N.C. University of Pécs, Hungary. Six Type 2 diabetic patients (mean age 59 ± 7 years) with severe ED (International Index of Erectile Function (IIEF) score: 7.7 ± 8.5) and impaired renal function (eGFR: 61 ± 16 ml/min) were involved. The thigh muscles of the patients were treated with HTEMS for 1 h 3 times per week for a duration of 4 weeks. Penile peak systolic velocity (PSV) (in the flaccid state and semi-rigid (after 10 mg intracavernous papaverine injection)), IIEF score, quality of life and laboratory parameters. At the beginning also the acute effect of HTEMS on penile PSV was investigated. Under basal conditions penile PSV was rather low. The first HTEMS session of the thighs induced an insignificant increase of PSV in the flaccid state (4.1 ± 1.2 to 6.3 ± 3.3 cm/s) and a significant rise of PSV in the semi-rigid penis (from 6.5 ± 2.5 to 8.9 ± 2.2 cm/s (p = 0.009)). After 4 weeks of HTEMS treatment, under basal conditions no significant change of penile PSV (flaccid and semirigid) was observed. Similarly, IIEF score did not improve over the time period (7.7 ± 8.1 vs. 6.7 ± 8.5, p > 0.05). Also, metabolic parameters and eGFR were not influenced. In a pilot study of diabetic patients with severe ED HTEMS of the thighs induced an acute rise of penile PSV in the semi-rigid state. However, after 4 weeks of HTEMS therapy the basal PSV and symptoms of ED were not improved.

Prevalence of gastroparesis-related symptoms in an unselected cohort of patients with Type 1 diabetes

BackgroundThe prevalence of diabetic gastroparesis is not well defined because of discrepancy between objective measurements, i.e. gastric emptying time, and symptoms experienced by patients. Furthermore most studies have been performed on small selected cohorts. ObjectiveTo determine the prevalence of clinical symptoms of diabetic gastroparesis in a large unselected cohort of out-patients with Type 1 diabetes. Methods1028 patients with Type 1 diabetes attending a specialized diabetes clinic were mailed a validated questionnaire; “patient assessment of upper gastrointestinal disorders-symptom severity index”, in which a subset of questions measures symptoms of gastroparesis (GCSI; Gastroparesis Cardinal Symptom Index). Response rate was 74.4% (n=765). All patients were classified according to presence or absence of late diabetic complications and clinical and paraclinical data were obtained. ResultsA GCSI Total Score ≥1.90 signified definite symptoms of gastroparesis (n=102) and patient charts were investigated for concomitant illness and/or medication influencing gastric emptying. In 30 patients an alternative etiology was revealed, leaving 72 (9.8%) patients with symptoms related to diabetic gastroparesis. Only 8 patients were previously diagnosed. HbA1c levels were significantly higher in patients with diabetic gastroparesis (8.4±1.3 vs. 8.2±1.2 respectively, p=0.02). Furthermore, patients with diabetic gastroparesis had more retinopathy (p=0.006) and peripheral polyneuropathy (16.7% vs. 6.7%, p<0.001) and there was a trend for diabetic nephropathy being more common (p=0.08). ConclusionsSymptoms of diabetic gastroparesis affect approximately 10% of patients with Type 1 diabetes in a specialized diabetes clinic and are associated with poor glycemic control and other late diabetic complications.

Hypothermia-Induced Peripheral Polyneuropathy After an Episode of Drowning

Hypothermia-Induced Peripheral Polyneuropathy After an Episode of Drowning

Behavioral, electrophysiological, and histopathological characterization of a severe murine chronic demyelinating polyneuritis model

The objective of this study was to define the behavioral, electrophysiological, and morphological characteristics of spontaneous autoimmune peripheral polyneuropathy (SAPP) in female B7-2 deficient non-obese diabetic (NOD) mice. A cohort of 77 female B7-2 deficient and 31 wild-type control NOD mice were studied from 18 to 40 weeks of age. At pre-defined time points, the dorsal caudal tail and sciatic motor nerve conduction studies (MNCS) were performed. Sciatic nerves were harvested for morphological evaluation. SAPP mice showed slowly progressive severe weakness in hind and forelimbs without significant recovery after 30 weeks of age. MNCS showed progressive reduction in mean compound motor action potential amplitudes and conduction velocities, and increase in mean total waveform duration from 24 to 27 weeks of age, peaking between 32 and 35 weeks of age. Toluidine blue-stained, semi-thin plastic-embedded sections demonstrated focal demyelination associated with mononuclear cell infiltration early in the disease course, with progressively diffuse demyelination and axonal loss associated with more intense mononuclear infiltration at peak severity. Immunohistochemistry confirmed macrophage-predominant inflammation. This study verifies SAPP as a progressive, unremitting chronic inflammatory demyelinating polyneuropathy with axonal loss.

Peripheral Nerve Involvement in Fukuyama Congenital Muscular Dystrophy

Fukuyama congenital muscular dystrophy is characterized by generalized muscle weakness and disturbances in central nervous system migration. Although this disorder is caused by mutations in the fukutin gene, which encodes a protein associated with the hypoglycosylation of α-dystroglycan, the specific functions of fukutin protein are largely unknown. In addition to being found in muscle and brain, α-dystroglycan is expressed in various other tissues including peripheral nerves, suggesting that deficiencies in fukutin may result in abnormal myelination of peripheral nerves due to the aberrant glycosylation of Schwann cell α-dystroglycan. This report describes a 7-year-old girl with Fukuyama congenital muscular dystrophy and demyelinating peripheral polyneuropathy.

099 Erythrocyte entrapped thymidine phosphorylase (EE-TP) therapy for mitochondrial neurogastrointestinal encephalomyopathy (MNGIE)

MNGIE is a fatal, autosomal recessive disorder caused by mutations in TYMP, a nuclear gene encoding thymidine phosphorylase (TP), leading to accumulation of thymidine (dThd) and deoxyuridine (dUrd) in all...

Enteroviral Meningitis and Concurrent Peripheral Motor Axonal Polyneuropathy

Enteroviral infections can cause acute flaccid paralysis resulting from anterior myelitis, but the occurrence of axonal polyneuropathy is not well described. We report an 8-year-old boy who presented with symmetric, ascending flaccid paralysis and was diagnosed with concurrent echovirus type 9 viral meningitis.

Cardiac Positron-Emission Tomography Images With an Amyloid-Specific Tracer in Familial Transthyretin-Related Systemic Amyloidosis

We report the case of a 32-year-old man who had suffered from orthostatic syncope and body weight loss since he was 27 years old. As years passed by, he also showed muscle weakness and abnormal sensations in both legs, hyporeflexia in 4 limbs, and autonomic failure (impotence, urinary and fecal incontinence, and edema in lower limbs) suggesting the presence of peripheral somatic and autonomic polyneuropathy. His mother, mother's father, and mother's paternal aunt also had similar symptoms. Both the sensory nerve action potential and the sensory nerve conduction velocity of his right sural nerve were low (1.26 μV and 47.2 m/s, respectively), and the motor nerve conduction velocity of his right tibial nerve was 41.1 m/s (normal >45 m/s). A DNA test on the man disclosed a missense mutation in the transthyretin gene (Ser50Arg), which is relatively rare …

A Case of Herpes Zoster Peripheral Polyneuropathy Manifested by Foot Drop in Chronic Myeloid Leukemia

In herpes zoster infection, neurological complications may be overlooked because pain is a more prominent symptom and because peripheral polyneuropathy associated with weakness is rare. A 57-year-old male visited our hospital, complaining of pain and skin eruptions on the right flank. He was diagnosed as having herpes zoster and the symptoms were alleviated by administration of acyclovir for a week. After three weeks, the herpes zoster relapsed. He was re-admitted and diagnosed with chronic myeloid leukemia (CML), and imatinib mesylate was prescribed for five weeks. Ten weeks after the onset of herpes zoster, bilateral foot drops and numbness of the right foot dorsum developed. Through an electrodiagnostic study, he was diagnosed as having peripheral polyneuropathy that was suspected to be caused by neural invasion by varicella zoster virus. After administration of famciclovir, not only the pain but also the neurologic symptoms improved. We herein report a case of peripheral polyneuropathy that was supposed to be related to herpes zoster.

Long‐term strategies for the treatment of Refsum's disease using therapeutic apheresis

Refsum's disease is a rare autosomal recessive disorder of fatty acid metabolism. Poorly metabolized phytanic acid accumulates in fatty tissues, including myelin sheaths and internal organs, leading to retinitis pigmentosa, peripheral polyneuropathy, cerebellar ataxia, and renal, cardiac or liver impairment. Dietary restriction of phytanic acid in some cases is not sufficient to prevent acute attacks and stabilize the progressive course. Phytanic acid bound to large low density lipoproteins (LDL) and very low density lipoproteins (VLDL) molecules offers the possibility of extracorporeal elimination by lipid apheresis. We report on the long-term lipid apheresis treatment of four patients with severe Refsum's disease. Retinitis pigmentosa, peripheral polyneuropathy, cerebellar ataxia, anosmia, and sensorineural hearing loss were major symptoms exhibiting a progressive course. Lipid apheresis was performed for 5-13 years without severe complications. Maximum levels of phytanic acid before commencing chronic lipid apheresis were >300 mg/l. During steady state with lipid apheresis, mean phytanic acid before treatments was 87 mg/l and was reduced to 36 mg/l. Mean reduction rate was 59% per treatment. In all patients, abnormal motor nerve conduction velocity with signs of chronic denervation improved, morphological and functional stabilization of eye involvement was observed. Lipid apheresis prevented the extension of the disease to previously unaffected organs in three patients. Extracorporeal elimination of lipoprotein-phytanic acid complexes by lipid apheresis represents a pathophysiologically guided therapeutic approach, resulting in long-term improvement or stabilization of overall rehabilitation in patients with progressive Refsum's disease.

Metronidazole induced encephalopathy with peripheral polyneuropathy in patient with spinal cord injury.

Metronidazole may produce a number of neurologic side effects including peripheral neuropathy, seizure, encephalopathy. We experienced neurological side effects of metronidazole. The 32-year-old female patient with spinal cord injury was diagnosed as encephalophathy and peripheral polyneuropathy resulting from complication of metronidazole. It was difficult to diagnose at first glance using clinical findings because of paraplegia due to spinal cord injury. But through magnetic resonance imaging with diffusion weighted imaging and electrophysiologic study, the patient showed to have characteristic abnormalities that of a person suffering from metronidazole-induced encephalopathy and peripheral polyneuropathy. Whether the symptoms were caused by a peripheral nerve lesion or MIE, the patient's paraplegia prevented to appear other symptoms, such as ataxic gait and seizure, from manifesting. In such case as this, an active differentiated diagnosis is crucial.