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Sample records for familial amyloidotic polyneuropathy

  1. Familial amyloidotic polyneuropathy without familial occurrence: carrier detection by the radioimmunoassay of variant transthyretin.

    PubMed Central

    Tanaka, M; Hirai, S; Matsubara, E; Okamoto, K; Morimatsu, M; Nakazato, M

    1988-01-01

    A 47 year old woman with familial amyloidotic polyneuropathy (FAP) is reported, without familial occurrence of the disease. Her 81 year old mother and 53 year old sister were proved to be asymptomatic carriers for variant transthyretin (TTR) by means of the radioimmunoassay. It is suggested that unknown factor(s) may play a role in preventing or delaying the onset of the disease, producing variations in sex and family incidence. In order to establish the diagnosis of non-hereditary primary amyloidotic polyneuropathy, it must be confirmed that variant TTR is absent in the serum of relatives. Images PMID:3379433

  2. Overexpression of Protocadherin-10 in Transthyretin-Related Familial Amyloidotic Polyneuropathy.

    PubMed

    Gonçalves, Nádia P; Martins, Diana; Saraiva, Maria João

    2016-07-01

    Overwhelming data suggest that oncogenic and neurodegenerative pathways share several altered cellular responses to insults such as oxidative stress, extracellular matrix remodeling, inflammation, or cell dyscommunication. Protocadherin-10 (Pcdh10) is an adhesion molecule found to protect against tumorigenesis and essential for axonal elongation and actin dynamics during development. Here, by using genome microarrays we identified for the first time Pcdh10 up-regulation in tissues from transgenic mouse models, cultured Schwann cells, and human samples from a familial form of peripheral neuropathy (familial amyloidotic polyneuropathy). Familial amyloidotic polyneuropathy is characterized by poor functional recovery and impaired nerve regenerative response after misfolding and deposition in the peripheral nervous system of mutant transthyretin. Not only increased transcriptional and translational Pcdh10 levels occurred in axons and Schwann cells of nerves with deposited transthyretin aggregates but the pattern also extended to associated cues of axon guidance like neuropilin-1 and F-actin. These findings suggest that Pcdh10 may influence subcellular actin cytoskeletal organization and axon-axon interactions in the course of familial amyloidotic polyneuropathy. Moreover, when preventing nonfibrillar transthyretin deposition with anakinra or transthyretin siRNA, Pcdh10 protein levels were reduced, highlighting its potential as a novel disease biomarker. Whether Pcdh10 overexpression in familial amyloidotic polyneuropathy represents a protective or deleterious response, enhancing survival or promoting cell death will need further investigation. PMID:27338109

  3. Radioimmunoassay for detecting abnormal prealbumin in the serum for diagnosis of familial amyloidotic polyneuropathy (Japanese type)

    SciTech Connect

    Nakazato, M.; Kangawa, K.; Minamino, N.; Tawara, S.; Matsuo, H.; Araki, S.

    1984-07-31

    In the serum of a Japanese patient with familial amyloidotic polyneuropathy (FAP), we demonstrated the presence of a prealbumin variant using a single amino acid substitution of a methionine residue for a valine at position 30. We have developed a highly sensitive and specific method for quantitative analysis of the prealbumin variant in the sera of FAP patients by using radioimmunoassay for a nonapeptide corresponding to subsequence (22-30) of the prealbumin variant. This peptide is produced from the prealbumin variant by cyanogen bromide cleavage followed by tryptic digestion. The serum administration of the prealbumin variant in five Japanese FAP patients ranges from 1.0 mg/dl to 7.8 mg/dl, which is 100 times or even higher than normal animals. This method should be helpful for an early diagnosis of this hereditary disease. 6 references, 4 figures, 1 table.

  4. Frequency of Cardiovascular Involvement in Familial Amyloidotic Polyneuropathy in Brazilian Patients

    PubMed Central

    Queiroz, Márcia Cavalcanti de Campos; Pedrosa, Roberto Coury; Berensztejn, Amanda Cardoso; Pereira, Basílio de Bragança; do Nascimento, Emília Matos; Duarte, Martha Maria Turano; Pereira-Junior, Pedro Paulo; Cruz, Marcia Waddington

    2015-01-01

    Background Familial amyloidotic polyneuropathy (FAP) is a rare disease diagnosed in Brazil and worldwide. The frequency of cardiovascular involvement in Brazilian FAP patients is unknown. Objective Detect the frequency of cardiovascular involvement and correlate the cardiovascular findings with the modified polyneuropathy disability (PND) score. Methods In a national reference center, 51 patients were evaluated with clinical examination, electrocardiography (ECG), echocardiography (ECHO), and 24-hour Holter. Patients were classified according to the modified PND score and divided into groups: PND 0, PND I, PND II, and PND > II (which included PND IIIa, IIIb, and IV). We chose the classification tree as the statistical method to analyze the association between findings in cardiac tests with the neurological classification (PND). Results ECG abnormalities were present in almost 2/3 of the FAP patients, whereas ECHO abnormalities occurred in around 1/3 of them. All patients with abnormal ECHO also had abnormal ECG, but the opposite did not apply. The classification tree identified ECG and ECHO as relevant variables (p < 0.001 and p = 0.08, respectively). The probability of a patient to be allocated to the PND 0 group when having a normal ECG was over 80%. When both ECG and ECHO were abnormal, this probability was null. Conclusions Brazilian patients with FAP have frequent ECG abnormalities. ECG is an appropriate test to discriminate asymptomatic carriers of the mutation from those who develop the disease, whereas ECHO contributes to this discrimination. PMID:26351985

  5. A study of 159 Portuguese patients with familial amyloidotic polyneuropathy (FAP) whose parents were both unaffected.

    PubMed Central

    Coelho, T; Sousa, A; Lourenço, E; Ramalheira, J

    1994-01-01

    We reviewed 1233 cases of familial amyloidotic polyneuropathy (FAP) from 489 Portuguese families registered at the Centro de Estudos de Paramiloidose, Porto, Portugal. It was found that in 159 cases, neither parent had shown symptoms of this hereditary dominant form of peripheral neuropathy. These cases appear to form a distinct group, with a later age at onset (mean 45.1 years, SD 12.0) than the group of patients with one affected parent (mean 31.2 years, SD 6.9) and a geographical origin not quite in the areas where the disease is most prevalent. Though this group is not significantly different from the general group of patients in clinical presentation at onset and severity of the disease, the average interval between onset and diagnosis (mean 4.5 years, SD 3.2) reflects the difficulties in diagnosing these patients in the absence of a positive family history. From the analysis of pedigrees and in spite of a large number of isolated cases, the occurrence of new mutations could not be proven, and it seems more likely that, in some families, the FAP gene may result in a milder expression or even remain "silent" for several generations. Further investigation of this discrepancy may prove to be important in elucidating the mechanisms involved in the pathogenetic process. PMID:8071954

  6. Analysis of mitochondrial haplogroups associated with TTR Val30Ala familial amyloidotic polyneuropathy in Chinese patients.

    PubMed

    Liu, Jing-Yao; Jiang, Xin-Mei; Zhang, Min; Guo, Ying-Jie

    2012-12-01

    Extracellular deposition of abnormal transthyretin (TTR) amyloid fibrils leads to familial amyloidotic polyneuropathy (FAP), an inherited autsomal dominant disease. A large number of protein variants, each caused by a different point mutation in the TTR gene have been identified, including TTR Val30Ala. Since the age of onset, organ involvement, and disease progression are highly variable in FAP, even among individuals with the same TTR genetic variation. it is likely that other genetic and environmental factors influence FAP disease phenotype. One study has found a relationship between mitochondrial haplogroups and age of onset of FAP. In this study, we wondered whether certain mitochondrial haplogroups were associated with the cases of TTR Val30Ala FAP in a Chinese population. Mitochondrial haplogroup analysis was performed on a group of patients and their relatives and on a group of healthy controls. All FAP probands were unrelated in their maternal lineages. The chi-squared test for independence found no difference in mitochondrial haplogroup distribution between FAP and control groups. This is the first study reporting frequency and distribution of different haplogroups in FAP in a Chinese population. Although the study group was small, TTR Val30Ala FAP in China seems unrelated to mitochondrial haplogroup. PMID:22784244

  7. [Effect of liver trasplantation on familial amyloidotic polyneuropathy (FAP) and its limt].

    PubMed

    Ando, Yukio

    2011-11-01

    Familial amyloidotic polyneuropathy (FAP) is a hereditary intractable disease induced by mutated transthyretin (TTR). Since TTR is predominantly synthesized by liver, liver transplantation has been performed to halt the clinical symptoms of FAP in the worldwide. It has been well documented that liver transplantation could halt the progression of FAP manifestations. However, the surgery could not prevent ocular symptoms and in some cases, cardiopathy and neuroparthy progressed even after liver trasplantation. Quantitative analyses for changes in the amount of amyloid deposition and ratio of wild type and variant type of TTR for autopsy transplanted FAP cases revealed that the amount of amyloid deposition decreased in most of the organs, but in heart and lung, the amount increased even after liver transplantation. In those organs, the ratio of wild type to variant TTR increased. Since liver transplantation has several problems, we are now performing several new therapeutic researches for FAP, such as development of drug stabilizing tetrameric form of TTR, siRNA therapy to stop TTR production, and low molecular compounds for preventing misfolding of TTR. PMID:22277510

  8. Outcome of exercise electrocardiography in familial amyloidotic polyneuropathy patients, Portuguese type, under evaluation for liver transplantation.

    PubMed

    Juneblad, Kristina; Näslund, Anna; Olofsson, Bert-Ove; Suhr, Ole B

    2004-09-01

    Familial amyloidotic polyneuropathy (FAP) is a dominantly inherited systemic amyloidosis caused by mutated transthyretin (TTR). Liver transplantation is currently the only available treatment that halts the progress of the disease. Cardiovascular complications are common in FAP, and cardiac arrhythmias are typical complications in FAP Val30Met. For patients with late onset FAP, as the Swedish patients, coronary heart disease has been found in several patients, and a QS complex is not an uncommon finding in FAP-patients ECG raising the suspicion of coronary heart disease. The aim of this study was to evaluate exercise ECG in FAP patients before transplantation with regard to mortality and morbidity. Thirty-eight FAP patients who underwent examination by exercise ECG, as part of the evaluation for liver transplantation were included in the study. Of these, 30 patients were transplanted, and the surviving patients were followed for at least 2 years. Exercise ECG was performed on bicycles with standard 12 leads. Non-parametric statistical analyses were used in all calculations. Six patients died 0-5.5 years after transplantation. They were older than the survivors (p < 0.01), but their duration of disease did not deviate from that of survivors (p = 0.8). They were also less able to increase their heart rates during exercise than the survivors (p < 0.05). For all transplanted patients, a significant relationship was found between patients' increase of heart rate, blood pressure and maximal workload, and the duration of disease and also for the PND-score, signifying that the outcome of exercise ECG predominantly was related to the patients autonomic and motor function, and not to their heart function. PMID:15523924

  9. Long-Term Outcomes and Complications of Trabeculectomy for Secondary Glaucoma in Patients with Familial Amyloidotic Polyneuropathy

    PubMed Central

    Kawaji, Takahiro; Inoue, Toshihiro; Hara, Ryuhei; Eiki, Daisuke; Ando, Yukio; Tanihara, Hidenobu

    2014-01-01

    Objective Secondary glaucoma is a serious complication in patients with transthyretin (TTR)-related familial amyloidotic polyneuropathy (FAP). We assessed the long-term outcomes and complications of trabeculectomy with mitomycin C (MMC) for secondary glaucoma associated with FAP. Methods Medical case records of Kumamoto University Hospital were retrospectively reviewed. Twenty-one eyes of 13 patients (10 with FAP ATTR Val30Met; 3 with FAP ATTR Tyr114Cys) underwent trabeculectomy with MMC and follow-up of at least 2 years. The primary outcome measure was Kaplan-Meier survival, with failure of this treatment being defined as an intraocular pressure (IOP) of ≤5 mm Hg or ≥22 mm Hg on two consecutive visits or as additional operations needed to reduce IOP. Secondary outcome measures included complications, bleb characteristics, and additional postoperative interventions required. Results The mean postoperative follow-up period was 5.7 years (range, 2.2–12.7 years). Kaplan-Meier analysis indicated probabilities of success of 0.76, 0.67, and 0.53 at 1, 2, and 3 years after operation, respectively. Significant complications included ocular decompression retinopathy in 7 eyes (33%) and bleb encapsulation in 10 eyes (48%). Twelve eyes (57%) needed additional surgery, such as bleb revision or trabeculectomy with MMC, to reduce IOP. Conclusions Trabeculectomy with MMC may not be optimal for patients with FAP-related glaucoma and may have several significant complications. PMID:24802803

  10. Characterisation of serum transthyretin by electrospray ionisation-ion mobility mass spectrometry: Application to familial amyloidotic polyneuropathy type I (FAP-I).

    PubMed

    Pont, Laura; Benavente, Fernando; Vilaseca, Marta; Giménez, Estela; Sanz-Nebot, Victoria

    2015-11-01

    Transthyretin (TTR) is a homotetrameric protein which is known to misfold and aggregate causing different types of amyloidosis, such as familial amyloidotic polyneuropathy type I (FAP-I). FAP-I is associated with a specific TTR mutant variant (TTR (Met30)) that can be easily detected analysing the monomeric forms of the mutant protein. Meanwhile, the mechanism of protein aggregation onset, which could be triggered by structural changes on the native tetrameric protein complex, remains uncertain. We developed and described herein a new sample pretreatment based on immunoprecipitation (IP) to purify TTR from serum under non-denaturing conditions. Later, a nano-electrospray ionization-ion mobility mass spectrometry (nano-ESI-IM-MS or IM-MS) method was optimised to analyse the protein complexes in serum samples from healthy controls and FAP-I patients. IM-MS allowed separation and characterisation of tetrameric, trimeric and dimeric TTR gas ions due to their differential drift time, which is related to ion size and charge. The tetramer-to-dimer abundance ratio was differential between healthy controls and FAP-I patients (asymptomatic, symptomatic and an iatrogenic patient originally without the mutation who received a liver transplant from an FAP-I patient), and was also indicative of the effectiveness of liver transplantation as a treatment for FAP-I. PMID:26452950

  11. Systemic senile amyloidosis. Identification of a new prealbumin (transthyretin) variant in cardiac tissue: immunologic and biochemical similarity to one form of familial amyloidotic polyneuropathy.

    PubMed Central

    Gorevic, P D; Prelli, F C; Wright, J; Pras, M; Frangione, B

    1989-01-01

    Isolated amyloid fibrils from three cases of systemic senile amyloidosis (SSA) contained subunit proteins with molecular masses of 14 (10-20%), 10-12 (60-80%), and 5-6 kD (5-10%) when fractionated under reducing and dissociating conditions. This grouping was identical to that seen in SKO, a case of familial amyloidotic polyneuropathy (FAP) studied earlier. Amino acid sequencing confirmed that SSA subunit proteins were in fact prealbumin (transthyretin). Complete sequence analysis of one SSA preparation revealed the presence of a new variant Pa (TTr) molecule with a single amino acid substitution of isoleucine for valine at position 122. Further studies used an antiserum specific for SKO IV, a subunit protein of SKO previously shown to correspond to carboxy-terminal 78 residues (positions 49-127) of (TTr). Anti-SKO IV reacted with SSA in tissue at equivalent dilutions to anti-Pa (TTr) and with the 10-12-kD fraction of SSA on Western blots; reactivity was blocked by SKO IV, but not by Pa (TTr). SSA is a form of systemic amyloidosis caused by tissue deposition of Pa (TTr) and its fragments, with shared conformational or subunit antigenicity to at least one form of FAP. Identification of a new variant Pa (TTr) molecule in one case suggests further that SSA may be a genetically determined disease expressed late in life. Images PMID:2646319

  12. ENDEAVOUR: Phase 3 Multicenter Study of Revusiran (ALN-TTRSC) in Patients With Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC)

    ClinicalTrials.gov

    2016-02-12

    Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC); Amyloidosis, Hereditary; Amyloid Neuropathies, Familial; Amyloid Neuropathies; Amyloidosis, Hereditary, Transthyretin-Related; Familial Transthyretin Cardiac Amyloidosis

  13. [Familial amyloid polyneuropathies: therapeutic issues].

    PubMed

    Adams, David; Cauquil, Cécile; Théaudin, Marie

    2012-10-01

    Patients with familial amyloidpolyneuropathies (FAP) require multidisciplinary neurologic and cardiologic management, including specific treatments to control the progression of systemic amyloidogenesis, symptomatic treatment of peripheral and autonomic neuropathies, and management of severe organ involvement (heart, eyes, kidneys). The first-line specific treatment of choice for met30 TTR-FAP is liver transplantation (LT) which suppresses the main source of mutant TTR, halts the progression of neuropathy in 70% of cases, and doubles the median survival time. Dual kidney-liver or heart-liver transplantation may be appropriate for patients with severe renal or cardiac failure. Tafamidis (Vyndaqel(R), Pfizer), a novel stabilizer of tetrameric TTR, has shown short-term effectiveness in slowing the progression of peripheral neuropathy in very early stages of met30 TTR-FAP This drug should thus be proposed for stage 1 symptomatic polyneuropathy. Other innovative medicines (RNA interference, antisense oligonucleotides) have been developed to block hepatic production of both mutant and wildtype TTR (noxious in late-onset forms of NAH after age 50 years), and to remove amyloid deposits (monoclonal anti-SAP). Clinical trials should first include patients with late-onset FAP or non-met30 TTR-FAP who are less responsive to LT7 and patients in whom Vyndaqel(R) is ineffective or inappropriate. Initial and periodic cardiac assessment is necessary, as cardiac impairment is inevitable and largely responsible for mortality. Symptomatic treatment is crucial to improve these patients' quality of life. Familial screening for carriers of the TTR gene mutation and regular clinical examination are essential to detect disease onset and to start specific therapy in a timely manner. PMID:23815018

  14. [Treatment of familial amyloid polyneuropathy].

    PubMed

    Adams, David; Samuel, Didier; Slama, Michel

    2012-09-01

    The treatment of familial amyloid polyneuropathies (FAP) is complex and requires a neurological and cardiological multidisciplinary coverage. It includes specific treatments to control the progression of the systemic amyloidogenesis, the symptomatic treatment of the peripheral and autonomic neuropathy (digestive, urinary, sexual, postural hypotension) and the treatment of organs severely involved by amyloidosis (heart, eyes, kidneys). First line specific treatment of met30 TTR-FAP is liver transplantation (LT) which allows to suppress the main source of mutant TTR, to stop the progression of the neuropathy in 70 % of cases at long-term (with an experience of 18 years) and to double the median survival. In case of severe renal or cardiac insufficiency, a double transplant kidney-liver or heart-liver can be discussed. The tafamidis (in temporary authorization of use in France) is a stabilizing medicine of the tetrameric TTR which showed in very early stages of met30 TTR-FAP short-term capacities to stop the progress of the peripheral neuropathy in 60 % of the cases versus 38 % with placebo. It should be proposed in case of contraindication of TH (age>70 years [20 % of the cases]), of very early stages (very low NIS-LL score), or for the period of wait of LT. Other innovative medicines issued from biopharmaceutical companies have been developed to block the hepatic production of both mutant and wild TTR which are noxious in the late forms NAH (>50 years old) (RNAi [RNA interference] therapeutics, AntiSens oligonucleotids), for removing the amyloid deposits (monoclonal antibody anti-SAP), or to slow down the formation of deposits of TTR and amyloidosis (combination of doxycycline-TUDCA). Clinical trials should be first addressed to the patients with a late onset of FAP or non-met30 TTR-FAP who are less responding to LT and patients with contraindications in the LT. Initial cardiac assessment and periodic cardiac investigations are important for the FAP according to the

  15. [Ocular involvement in familial amyloid polyneuropathy].

    PubMed

    Rousseau, A; Kaswin, G; Adams, D; Cauquil, C; Théaudin, M; Mincheva, Z; M'garrech, M; Labetoulle, M; Barreau, E

    2013-11-01

    Familial amyloid polyneuropathy (FAP) or transthyretin (TTR) amyloid polyneuropathy is a progressive sensorimotor and autonomic neuropathy of adult onset, which is transmitted as an autosomal dominant trait. In addition to neurologic symptoms, FAP may be associated with weight loss, cardiac and renal failure and ocular complications. FAP is a devastating disease, causing death within 10years after the first symptoms. The TTR Val30Met mutation is the most common of more than 100 amyloidogenic mutations identified worldwide. Liver transplantation (LT) is currently the only treatment for preventing synthesis of the amyloidogenic variants of TTR. LT can halt progression of the neuropathy in up to 70% of cases and doubles the overall median survival of young Val30Met patients. Oral administration of tafamidis, which prevents deposition of mutated TTR, is now available to delay neurologic complications in early stages of the disease. Ocular manifestations of FAP are frequent and mainly include keratoconjunctivitis sicca, secondary glaucoma, vitreous deposits and pupillary abnormalities. Retinal and choroidal vascular abnormalities are more rare. Since ocular TTR is synthesized, at least in part, in the retinal pigment epithelium, LT does not influence the course of ocular involvement. The effects of tafamidis on the latter are still unknown. Because LT and symptomatic treatments greatly improve life expectancy of patients with FAP, ocular involvement is becoming a more frequent challenge to address. This review summarizes the pathophysiology, clinical findings and possible treatments of ocular manifestations of FAP. PMID:24144522

  16. Multiple familial lipomatosis with polyneuropathy, an inherited dominant condition.

    PubMed

    Stoll, C; Alembik, Y; Truttmann, M

    1996-01-01

    A 22-year-old man had polyneuropathy, facial dysmorphia, atopia and multiple lipomatosis. His mother had neuropathy but not lipomatosis as two of her first cousins. The proband's grandmother had multiple lipomatosis as her own mother and a sister of her mother, but they didn't have neuropathy. This family is an example of a dominant syndrome the principle features of which are polyneuropathy. Variable expression could account for the phenotypic differences, combined with multiple lipomatosis. PMID:9037345

  17. Tafamidis for transthyretin familial amyloid polyneuropathy

    PubMed Central

    Maia, Luis F.; Martins da Silva, Ana; Waddington Cruz, Marcia; Planté-Bordeneuve, Violaine; Lozeron, Pierre; Suhr, Ole B.; Campistol, Josep M.; Conceição, Isabel Maria; Schmidt, Hartmut H.-J.; Trigo, Pedro; Kelly, Jeffery W.; Labaudinière, Richard; Chan, Jason; Packman, Jeff; Wilson, Amy; Grogan, Donna R.

    2012-01-01

    Objectives: To evaluate the efficacy and safety of 18 months of tafamidis treatment in patients with early-stage V30M transthyretin familial amyloid polyneuropathy (TTR-FAP). Methods: In this randomized, double-blind trial, patients received tafamidis 20 mg QD or placebo. Coprimary endpoints were the Neuropathy Impairment Score–Lower Limbs (NIS-LL) responder analysis (<2-point worsening) and treatment-group difference in the mean change from baseline in Norfolk Quality of Life–Diabetic Neuropathy total score (TQOL) in the intent-to-treat (ITT) population (n = 125). These endpoints were also evaluated in the efficacy-evaluable (EE; n = 87) population. Secondary endpoints, including changes in neurologic function, nutritional status, and TTR stabilization, were analyzed in the ITT population. Results: There was a higher-than-anticipated liver transplantation dropout rate. No differences were observed between the tafamidis and placebo groups for the coprimary endpoints, NIS-LL responder analysis (45.3% vs 29.5% responders; p = 0.068) and change in TQOL (2.0 vs 7.2; p = 0.116) in the ITT population. In the EE population, significantly more tafamidis patients than placebo patients were NIS-LL responders (60.0% vs 38.1%; p = 0.041), and tafamidis patients had better-preserved TQOL (0.1 vs 8.9; p = 0.045). Significant differences in most secondary endpoints favored tafamidis. TTR was stabilized in 98% of tafamidis and 0% of placebo patients (p < 0.0001). Adverse events were similar between groups. Conclusions: Although the coprimary endpoints were not met in the ITT population, tafamidis was associated with no trend toward more NIS-LL responders and a significant reduction in worsening of most neurologic variables, supporting the hypothesis that preventing TTR dissociation can delay peripheral neurologic impairment. Classification of evidence: This study provides Class II evidence that 20 mg tafamidis QD was associated with no difference in clinical progression in

  18. Management of asymptomatic gene carriers of transthyretin familial amyloid polyneuropathy.

    PubMed

    Schmidt, Hartmut H-J; Barroso, Fabio; González-Duarte, Alejandra; Conceição, Isabel; Obici, Laura; Keohane, Denis; Amass, Leslie

    2016-09-01

    Transthyretin familial amyloid polyneuropathy (TTR-FAP) is a rare, severe, and irreversible, adult-onset, hereditary disorder caused by autosomal-dominant mutations in the TTR gene that increase the intrinsic propensity of transthyretin protein to misfold and deposit systemically as insoluble amyloid fibrils in nerve tissues, the heart, and other organs. TTR-FAP is characterized by relentless, progressively debilitating polyneuropathy, and leads to death, on average, within 10 years of symptom onset without treatment. With increased availability of disease-modifying treatment options for a wider spectrum of patients with TTR-FAP, timely detection of the disease may offer substantial clinical benefits. This review discusses mutation-specific predictive genetic testing in first-degree relatives of index patients diagnosed with TTR-FAP and the structured clinical follow-up of asymptomatic gene carriers for prompt diagnosis and early therapeutic intervention before accumulation of substantial damage. Muscle Nerve 54: 353-360, 2016. PMID:27273296

  19. "Red-flag" symptom clusters in transthyretin familial amyloid polyneuropathy.

    PubMed

    Conceição, Isabel; González-Duarte, Alejandra; Obici, Laura; Schmidt, Hartmut H-J; Simoneau, Damien; Ong, Moh-Lim; Amass, Leslie

    2016-03-01

    Transthyretin familial amyloid polyneuropathy (TTR-FAP) is a rare, progressive, life-threatening, hereditary disorder caused by mutations in the transthyretin gene and characterized by extracellular deposition of transthyretin-derived amyloid fibrils in peripheral and autonomic nerves, heart, and other organs. TTR-FAP is frequently diagnosed late because the disease is difficult to recognize due to phenotypic heterogeneity. Based on published literature and expert opinion, symptom clusters suggesting TTR-FAP are reviewed, and practical guidance to facilitate earlier diagnosis is provided. TTR-FAP should be suspected if progressive peripheral sensory-motor neuropathy is observed in combination with one or more of the following: family history of a neuropathy, autonomic dysfunction, cardiac hypertrophy, gastrointestinal problems, inexplicable weight loss, carpal tunnel syndrome, renal impairment, or ocular involvement. If TTR-FAP is suspected, transthyretin genotyping, confirmation of amyloid in tissue biopsy, large- and small-fiber assessment by nerve conduction studies and autonomic system evaluations, and cardiac testing should be performed. PMID:26663427

  20. Aqueous humor erythropoietin levels in open-angle glaucoma patients with and without TTR V30M familial amyloid polyneuropathy

    PubMed Central

    Moreira, Luciana M.; Oliveira, João C.; Menéres, Maria J.; Pessoa, Bernardete B.; Matos, Maria E.; Costa, Paulo P.; Torres, Paulo A.

    2014-01-01

    Purpose Glaucoma is the leading cause of irreversible blindness in familial amyloidotic polyneuropathy (FAP) patients. Erythropoietin (EPO) is a cytokine that has been shown to play a role in neuroprotection and is endogenously produced in the eye. EPO levels in the aqueous humor are increased in eyes with glaucoma. In this study, we evaluated the EPO concentration in the aqueous humor of FAP and non-FAP patients, with and without glaucoma. Methods Undiluted aqueous humor samples were obtained from 42 eyes that underwent glaucoma surgery, phacoemulsification, or vitrectomy. EPO concentration in the aqueous humor and blood were measured using the Immulite 2000 Xpi using an automatic analyzer (Siemens Healthcare Diagnostics). Results The mean EPO concentration in the aqueous humor of non-FAP glaucoma eyes group 2 (75.73±13.25 mU/ml) was significantly higher than non-FAP cataract eyes (17.22±5.33 mU/ml; p<0.001), FAP glaucoma eyes (18.82±10.16 mU/ml; p<0.001), and FAP nonglaucoma eyes (20.62±6.22 mU/ml; p<0.001). There was no statistically significant difference between FAP nonglaucoma eyes versus non-FAP cataract eyes (p = 0.23) and FAP glaucoma eyes versus FAP nonglaucoma eyes (p = 0.29). In the glaucoma groups, there was no correlation between the aqueous humor EPO concentration and the ocular pressure (p = 0.95) and mean deviation (p = 0.41). There was no correlation between the EPO serum concentration and EPO aqueous humor concentration in our patients (p = 0.77). Conclusions Unlike other glaucomatous patients, FAP patients with glaucoma do not show increased and potentially neuroprotective endocular EPO production in the aqueous humor and may need more aggressive glaucoma management. PMID:25018619

  1. [Perioperative management for liver transplant in a patient with familial amyloid polyneuropathy with heart involvement].

    PubMed

    López-Herrera Rodríguez, D; Guerrero Domínguez, R; Mellado Miras, P; Gómez Sosa, L

    2015-01-01

    Familial amyloid polyneuropathy (FAP) is a systemic amyloidosis caused by mutated transthyretin. Cardiac amyloidosis, the major prognostic determinant in systemic amyloidosis, is characterized by infiltration of the myocardium, leading to cardiomyopathy and conduction disturbances. Liver transplantation is the only curative option for patients with FAP. The case is presented of a 36-year-old patient with type i FAP with cardiac involvement, proposed for liver transplant surgery, which was successfully performed without any preoperative event of interest. PMID:24742789

  2. Genotypic and phenotypic presentation of transthyretin-related familial amyloid polyneuropathy (TTR-FAP) in Turkey.

    PubMed

    Durmuş-Tekçe, Hacer; Matur, Zeliha; Mert Atmaca, Murat; Poda, Mehves; Çakar, Arman; Hıdır Ulaş, Ümit; Oflazer-Serdaroğlu, Piraye; Deymeer, Feza; Parman, Yesim G

    2016-07-01

    Transthyretin-related familial amyloid polyneuropathy (TTR-FAP) is an autosomal dominant disorder caused by mutations of the transthyretin (TTR) gene. The mutant amyloidogenic transthyretin protein causes the systemic accumulation of amyloid fibrils that result in organ dysfunction. TTR-associated FAP is a progressive and fatal disease, if left untreated, and should be considered in the differential diagnosis of any person presenting with a progressive polyneuropathy, particularly with accompanying autonomic involvement. The clinical, electrophysiological, histopathological, and genetic characteristics of 17 patients from Turkey (5 female, 13 male) from nine families with polyneuropathy and mutations in TTR were evaluated. Sequence analysis of the TTR gene revealed five mutations (Val30Met, Glu89Gln, Gly53Glu, Glu54Gly and Gly47Glu). Mean age at disease onset was 40.4 ± 13.9 years (range 21-66 years). The most commonly reported initial complaint was paresthesia in the feet (asymmetric in three patients). Three patients (2 male) with the Glu89Gln mutation presented with carpal tunnel syndrome. Two patients with the Gly53Glu mutation showed episodes of dysarthria and hemiparesis, consistent with this genotype. Seven patients died during the period of follow-up as a result of systemic involvement. Our study suggests that a cohort of patients from Turkey with TTR-FAP exhibits clinical and genetic heterogeneity. PMID:27238058

  3. Severe heart disease in an unusual case of familial amyloid polyneuropathy type I.

    PubMed

    Oliveira Santos, Miguel; Brito, Dulce

    2013-09-01

    Familial amyloid polyneuropathy type I (FAP type I) is a rare hereditary systemic amyloidosis caused by the Val30Met mutation in the transthyretin (TTR) gene. The clinical onset and spectrum are variable and depend on phenotypic heterogeneity. Cardiac complications (dysrhythmias and conduction disturbances, cardiomyopathy and dysautonomia) indicate a poor prognosis, even after liver transplantation. We report an atypical case of FAP type I, highlighting the severe cardiac involvement and its complications. Early diagnosis of amyloid heart disease is increasingly important in the context of several clinical trials of promising new and experimental drugs. PMID:23993291

  4. Exome Sequencing and Gene Prioritization Correct Misdiagnosis in a Chinese Kindred with Familial Amyloid Polyneuropathy

    PubMed Central

    Chen, Hui; Zhou, Xueya; Wang, Jing; Wang, Xi; Liu, Liyang; Wu, Shinan; Li, Tengyan; Chen, Si; Yang, Jingwen; Sham, Pak Chung; Zhu, Guangming; Zhang, Xuegong; Wang, Binbin

    2016-01-01

    Inherited neuropathies show considerable heterogeneity in clinical manifestations and genetic etiologies, and are therefore often difficult to diagnose. Whole-exome sequencing (WES) has been widely adopted to make definite diagnosis of unclear conditions, with proven efficacy in optimizing patients’ management. In this study, a large Chinese kindred segregating autosomal dominant polyneuropathy with incomplete penetrance was ascertained through a patient who was initially diagnosed as Charcot-Marie-Tooth disease. To investigate the genetic cause, forty-six living family members were genotyped by SNP microarrays, and one confirmed patient was subject to WES. Through systematic computational prioritization, we identified a missense mutation c.G148T in TTR gene which results in a p.V50L substitution known to cause transthyretin-related familial amyloid polyneuropathy. Co-segregation analysis and clinical follow-up confirmed the new diagnosis, which suggested new therapeutic options to the patients and informed high risk family members. This study confirms WES as a powerful tool in translational medicine, and further demostrates the practical utility of gene prioritization in narrowing the scope of causative mutation. PMID:27212199

  5. Exome Sequencing and Gene Prioritization Correct Misdiagnosis in a Chinese Kindred with Familial Amyloid Polyneuropathy.

    PubMed

    Chen, Hui; Zhou, Xueya; Wang, Jing; Wang, Xi; Liu, Liyang; Wu, Shinan; Li, Tengyan; Chen, Si; Yang, Jingwen; Sham, Pak Chung; Zhu, Guangming; Zhang, Xuegong; Wang, Binbin

    2016-01-01

    Inherited neuropathies show considerable heterogeneity in clinical manifestations and genetic etiologies, and are therefore often difficult to diagnose. Whole-exome sequencing (WES) has been widely adopted to make definite diagnosis of unclear conditions, with proven efficacy in optimizing patients' management. In this study, a large Chinese kindred segregating autosomal dominant polyneuropathy with incomplete penetrance was ascertained through a patient who was initially diagnosed as Charcot-Marie-Tooth disease. To investigate the genetic cause, forty-six living family members were genotyped by SNP microarrays, and one confirmed patient was subject to WES. Through systematic computational prioritization, we identified a missense mutation c.G148T in TTR gene which results in a p.V50L substitution known to cause transthyretin-related familial amyloid polyneuropathy. Co-segregation analysis and clinical follow-up confirmed the new diagnosis, which suggested new therapeutic options to the patients and informed high risk family members. This study confirms WES as a powerful tool in translational medicine, and further demostrates the practical utility of gene prioritization in narrowing the scope of causative mutation. PMID:27212199

  6. Ophthalmic manifestations in a Chinese family with familial amyloid polyneuropathy due to a TTR Gly83Arg mutation

    PubMed Central

    Liu, T; Zhang, B; Jin, X; Wang, W; Lee, J; Li, J; Yuan, H; Cheng, X

    2014-01-01

    Purpose To describe the characteristic ophthalmic phenotypes of a large Chinese family with familial amyloid polyneuropathy due to a missense mutation in transthyretin (TTR) (c.307 C>G). Methods Twenty-seven individuals (12 affected, 15 unaffected) from a five-generation Chinese family underwent general medical examination and comprehensive ophthalmic examination, including best correct visual acuity, intraocular pressure measurements, Schirmer test, slitlamp examination, fundoscopy, and ocular ultrasonography. Histological examination of vitreous biopsies using Congo red staining and immunohistochemistry was performed. Cardiovascular magnetic resonance (CMR), electrocardiogram, and echocardiogram were used to evaluate cardiac amyloidosis. Electromyography was used to evaluate nerve function. All four exons of TTR were amplified by PCR, sequenced using a Bigdye terminator v3.1 cycle sequencing kit and analyzed on an ABI 3700XL Genetic Analyzer. Results All 12 affected individuals in the family had ocular manifestations, including severe vitreous opacities, secondary glaucoma, xerophthalmia, dyscoria, and attenuated retinal arteries. Congo red staining demonstrated amyloid deposits in the vitreous, and immunohistochemical staining confirmed the deposition of TTR proteins in the vitreous. Twelve individuals had polyneuropathy, and electromyography detected functional damage in peripheral nerves. One individual was diagnosed with cardiac amyloidosis by CMR. Direct sequencing revealed the heterozygous missense mutation in TTR (c.307 C>G p.Gly83Arg) in all 12 affected individuals. The mutation co-segregated with the disease phenotype and was absent in 100 normal controls. Conclusions Vitreous opacity is very common in patients with the TTR Gly83Arg mutation; other clinical characteristics associated with the mutation include polyneuropathy and cardiac amyloidosis. PMID:24113303

  7. Norfolk QOL-DN: validation of a patient reported outcome measure in transthyretin familial amyloid polyneuropathy.

    PubMed

    Vinik, Etta J; Vinik, Aaron I; Paulson, James F; Merkies, Ingemar S J; Packman, Jeff; Grogan, Donna R; Coelho, Teresa

    2014-06-01

    The Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN) questionnaire is an instrument to assess QOL in diabetic polyneuropathy. The objective of this observational, cross-sectional study in 61 patients with V30M transthyretin familial amyloid polyneuropathy (TTR-FAP) and 16 healthy volunteers was to validate the Norfolk QOL-DN for assessment of QOL in TTR-FAP. Comparisons were conducted to identify the best items to discriminate disease stages and assess which individual Norfolk domains (symptoms, large fiber, small fiber, autonomic, and activities of daily living) would be most affected by disease stage. Analysis of individual items revealed a significant pattern of discrimination among disease stages (p < 0.001). Total QOL scores increased (indicating worsening) with duration of symptoms, with a steeper increase observed earlier in the course of disease. Significant correlations were observed between each Norfolk domain and other measures of neurological function. Limitations include cross-sectional study design, low patient numbers in this rare disease, and the ordinal-based character of the metric used; future areas to explore include item response theory approaches such as Rasch analysis. These results suggest the Norfolk QOL-DN is a reliable indicator of the impact of disease severity on QOL in patients with TTR-FAP. PMID:24738700

  8. In vivo detection of nerve injury in familial amyloid polyneuropathy by magnetic resonance neurography.

    PubMed

    Kollmer, Jennifer; Hund, Ernst; Hornung, Benjamin; Hegenbart, Ute; Schönland, Stefan O; Kimmich, Christoph; Kristen, Arnt V; Purrucker, Jan; Röcken, Christoph; Heiland, Sabine; Bendszus, Martin; Pham, Mirko

    2015-03-01

    Transthyretin familial amyloid polyneuropathy is a rare, autosomal-dominant inherited multisystem disorder usually manifesting with a rapidly progressive, axonal, distally-symmetric polyneuropathy. The detection of nerve injury by nerve conduction studies is limited, due to preferential involvement of small-fibres in early stages. We investigated whether lower limb nerve-injury can be detected, localized and quantified in vivo by high-resolution magnetic resonance neurography. We prospectively included 20 patients (12 male and eight female patients, mean age 47.9 years, range 26-66) with confirmed mutation in the transthyretin gene: 13 with symptomatic polyneuropathy and seven asymptomatic gene carriers. A large age- and sex-matched cohort of healthy volunteers served as controls (20 male and 20 female, mean age 48.1 years, range 30-73). All patients received detailed neurological and electrophysiological examinations and were scored using the Neuropathy Impairment Score-Lower Limbs, Neuropathy Deficit and Neuropathy Symptom Score. Magnetic resonance neurography (3 T) was performed with large longitudinal coverage from proximal thigh to ankle-level and separately for each leg (140 axial slices/leg) by using axial T2-weighted (repetition time/echo time = 5970/55 ms) and dual echo (repetition time 5210 ms, echo times 12 and 73 ms) turbo spin echo 2D sequences with spectral fat saturation. A 3D T2-weighted inversion-recovery sequence (repetition time/echo time 3000/202 ms) was acquired for imaging of the spinal nerves and lumbar plexus (50 axial slice reformations). Precise manual segmentation of the spinal/sciatic/tibial/common peroneal nerves was performed on each slice. Histogram-based normalization of nerve-voxel signal intensities was performed using the age- and sex-matched control group as normative reference. Nerve-voxels were subsequently classified as lesion-voxels if a threshold of >1.2 (normalized signal-intensity) was exceeded. At distal thigh level

  9. Vitreous Amyloidosis as the Presenting Symptom of Familial Amyloid Polyneuropathy TTR Val30Met in a Portuguese Patient

    PubMed Central

    Seca, Mariana; Ferreira, Natália; Coelho, Teresa

    2014-01-01

    Familial amyloid polyneuropathy (FAP) is a group of disorders characterized by the extracellular deposition of amyloid substance in various tissues. The peripheral nervous system and the heart are the main target organs, but the eye may also be involved. We report a case of vitreous amyloidosis as the first manifestation of FAP in a 66-year-old Portuguese man without a family history. PMID:24748873

  10. Familial Amyloid Polyneuropathy Type IV (FINNISH) with Rapid Clinical Progression in an Iranian Woman: A Case Report

    PubMed Central

    Babaei-Ghazani, Arash; Eftekharsadat, Bina

    2016-01-01

    Familial amyloid polyneuropathy (FAP) type IV (FINNISH) is a rare clinical entity with challenging neuropathy and cosmetic deficits. Amyloidosis can affect peripheral sensory, motor, or autonomic nerves. Nerve lesions are induced by deposits of amyloid fibrils and treatment approaches for neuropathy are challenging. Involvement of cranial nerves and atrophy in facial muscles is a real concern in daily life of such patients. Currently, diagnosis of neuropathy can be made by electrodiagnostic studies and diagnosis of amyloidosis can be made by genetic testing or by detection of amyloid deposition in abdominal fat pad, rectal, or nerve biopsies. It is preferable to consider FAP as one of the differential diagnosis of a case presented with multiple cranial nerves symptoms. The authors present a case of familial amyloid polyneuropathy (FAP) type IV with severe involvement of multiple cranial nerves, peripheral limb neuropathy, and orthostatic hypotension. PMID:27217609

  11. Familial Amyloid Polyneuropathy Type IV (FINNISH) with Rapid Clinical Progression in an Iranian Woman: A Case Report.

    PubMed

    Babaei-Ghazani, Arash; Eftekharsadat, Bina

    2016-05-01

    Familial amyloid polyneuropathy (FAP) type IV (FINNISH) is a rare clinical entity with challenging neuropathy and cosmetic deficits. Amyloidosis can affect peripheral sensory, motor, or autonomic nerves. Nerve lesions are induced by deposits of amyloid fibrils and treatment approaches for neuropathy are challenging. Involvement of cranial nerves and atrophy in facial muscles is a real concern in daily life of such patients. Currently, diagnosis of neuropathy can be made by electrodiagnostic studies and diagnosis of amyloidosis can be made by genetic testing or by detection of amyloid deposition in abdominal fat pad, rectal, or nerve biopsies. It is preferable to consider FAP as one of the differential diagnosis of a case presented with multiple cranial nerves symptoms. The authors present a case of familial amyloid polyneuropathy (FAP) type IV with severe involvement of multiple cranial nerves, peripheral limb neuropathy, and orthostatic hypotension. PMID:27217609

  12. “Red‐flag” symptom clusters in transthyretin familial amyloid polyneuropathy

    PubMed Central

    González‐Duarte, Alejandra; Obici, Laura; Schmidt, Hartmut H.‐J.; Simoneau, Damien; Ong, Moh‐Lim; Amass, Leslie

    2016-01-01

    Abstract Transthyretin familial amyloid polyneuropathy (TTR‐FAP) is a rare, progressive, life‐threatening, hereditary disorder caused by mutations in the transthyretin gene and characterized by extracellular deposition of transthyretin‐derived amyloid fibrils in peripheral and autonomic nerves, heart, and other organs. TTR‐FAP is frequently diagnosed late because the disease is difficult to recognize due to phenotypic heterogeneity. Based on published literature and expert opinion, symptom clusters suggesting TTR‐FAP are reviewed, and practical guidance to facilitate earlier diagnosis is provided. TTR‐FAP should be suspected if progressive peripheral sensory‐motor neuropathy is observed in combination with one or more of the following: family history of a neuropathy, autonomic dysfunction, cardiac hypertrophy, gastrointestinal problems, inexplicable weight loss, carpal tunnel syndrome, renal impairment, or ocular involvement. If TTR‐FAP is suspected, transthyretin genotyping, confirmation of amyloid in tissue biopsy, large‐ and small‐fiber assessment by nerve conduction studies and autonomic system evaluations, and cardiac testing should be performed. PMID:26663427

  13. High 99mTc-DPD myocardial uptake in a patient with apolipoprotein AI-related amyloidotic cardiomyopathy.

    PubMed

    Quarta, Candida Cristina; Obici, Laura; Guidalotti, Pier Luigi; Pieroni, Maurizio; Longhi, Simone; Perlini, Stefano; Verga, Laura; Merlini, Giampaolo; Rapezzi, Claudio

    2013-03-01

    Amyloidotic cardiomyopathy is still a widely underdiagnosed condition that usually requires endomyocardial biopsy (EMB) for a definite diagnosis. 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) has proven highly sensitive for detecting amyloidotic cardiomyopathy due to transthyretin-related amyloid deposition. Herein we report the first description of the (99mTc-DPD scintigraphy profile in a patient with suspected amyloidotic cardiomyopathy and a final EMB- and genetically-proven diagnosis of familial apolipoprotein AI amyloidosis due to Leu174Ser variant. PMID:23231421

  14. Long-term quantitative evaluation of liver transplantation in familial amyloid polyneuropathy (Portuguese V30M).

    PubMed

    de Carvalho, Mamede; Conceição, Isabel; Bentes, Carla; Luís, M L Sales

    2002-06-01

    Familial amyloid polyneuropathy (FAP) is associated with massive endoneurial and extracellular deposition of amyloid, which isformed from a mutated transthyretin (TTR) protein. Ninety percent of TTR protein is produced in liver. Liver transplantation (LT) is the only treatment that can halt FAP clinical progression. We studied 35 LT patients. The mean age of the first symptoms was 36.6 years (ranging from 27 to 56), 19 were males, and 16 females, they underwent LT after a mean time of 5 years of symptomatic disease. Fifteen patients followed for more than 24 months after LT had periodic evaluations with clinical and neurophysiological scores (CS and NS). Ten were first evaluated before LT (mean follow-up time of 44 months after LT), and 5 were evaluated only after LT (or a mean time of 41 months). Five patients were followed periodically before LT (mean time of 44 months) to study the natural course of this condition. The mortality rate was of 14% in the first 6 months and was related to known complications of the surgery. No deaths occurred in the period 6 months to 1 year after LT. Five patients (14%) died 1-2 years after LT, 4 of whom were transplanted in advance stages. In the survival group, CS tended to stabilize shortly after LT and to remain invariable later on. The NSprogressed in the first year following LT, and subsequently it did not increase significantly. LT changed the natural course of FAP-I. PMID:12440485

  15. First European consensus for diagnosis, management, and treatment of transthyretin familial amyloid polyneuropathy

    PubMed Central

    Adams, David; Suhr, Ole B.; Hund, Ernst; Obici, Laura; Tournev, Ivailo; Campistol, Josep M.; Slama, Michel S.; Hazenberg, Bouke P.; Coelho, Teresa

    2016-01-01

    Purpose of review Early and accurate diagnosis of transthyretin familial amyloid polyneuropathy (TTR-FAP) represents one of the major challenges faced by physicians when caring for patients with idiopathic progressive neuropathy. There is little consensus in diagnostic and management approaches across Europe. Recent findings The low prevalence of TTR-FAP across Europe and the high variation in both genotype and phenotypic expression of the disease means that recognizing symptoms can be difficult outside of a specialized diagnostic environment. The resulting delay in diagnosis and the possibility of misdiagnosis can misguide clinical decision-making and negatively impact subsequent treatment approaches and outcomes. Summary This review summarizes the findings from two meetings of the European Network for TTR-FAP (ATTReuNET). This is an emerging group comprising representatives from 10 European countries with expertise in the diagnosis and management of TTR-FAP, including nine National Reference Centres. The current review presents management strategies and a consensus on the gold standard for diagnosis of TTR-FAP as well as a structured approach to ongoing multidisciplinary care for the patient. Greater communication, not just between members of an individual patient's treatment team, but also between regional and national centres of expertise, is the key to the effective management of TTR-FAP. PMID:26734952

  16. Endoscopic Findings of Small-Bowel Lesions in Familial Amyloid Polyneuropathy

    PubMed Central

    Asakura, Kensuke; Yanai, Shunichi; Nakamura, Shotaro; Kawaski1, Keisuke; Eizuka, Makoto; Ishida, Kazuyuki; Sugai, Tamotsu; Ueda, Mitsuharu; Yamashita, Taro; Ando, Yukio; Matsumoto, Takayuki

    2016-01-01

    Abstract Familial amyloid polyneuropathy (FAP) is an autosomal dominant disease associated with the mutations in the transthyretin gene. To date, the endoscopic findings of the small-bowel lesions of FAP have never been described. We report a rare case of FAP with gastrointestinal involvement. A 71-year-old woman complaining of refractory diarrhea for 1 year was referred to our institution. She had sensory disturbance, movement disorder due to muscle weakness, and autonomic nervous system disorders including orthostatic hypotension and dysuria. Her eldest sister had cardiac amyloidosis. Small-bowel radiography and retrograde double-balloon endoscopy (DBE) revealed that fine granular protrusions were diffusely observed both in the jejunum and ileum. Histologic examination of the biopsy specimens obtained from the small bowel revealed perivascular amyloid deposits mainly in the muscularis mucosae and submucosa, which were immunoreactive with transthyretin antibodies. Analysis of the genomic DNA showed a heterozygous Gly47Val mutation in the transthyretin gene. Thus a diagnosis of FAP was established. Diffuse fine granular protrusions in the jejunum and the ileum visualized by small-bowel radiography and DBE may be characteristic of FAP. Multiple biopsies from the gastrointestinal mucosa are recommended for the definitive histologic diagnosis of FAP. PMID:26986100

  17. Ocular Manifestations and Therapeutic Options in Patients with Familial Amyloid Polyneuropathy: A Systematic Review

    PubMed Central

    Martins, A. C.; Rosa, A. M.; Costa, E.; Tavares, C.; Quadrado, M. J.; Murta, J. N.

    2015-01-01

    Purpose. This paper aims to review the morphological and functional characteristics of patients affected by familial amyloid polyneuropathy (FAP), with greater focus on type I and its progression after liver transplantation. We also analyse therapeutic options for the ophthalmic manifestations. Methods. The literature from 2002 through 2015 was reviewed, with a total of 45 articles studied, using the key terms related to amyloidosis and its therapeutic approaches. Information was collated, evaluated, critically assessed, and then summarised in its present form. Pathophysiology and Treatment. FAP results from mutation of the transthyretin gene, with Val30Met being the most frequent substitution. The symptoms are those typical of a sensorimotor autonomic neuropathy and can be halted with liver transplantation. Nowadays there are new medical therapies that delay the progression of the systemic neuropathy. However, there are still no options to avoid ocular disease. Conclusion. The main ocular manifestations in patients with FAP type I are amyloid deposition in the vitreous, dry eye, and secondary glaucoma. Despite liver transplantation, eye synthesis of amyloid persists and is associated with progressive ocular manifestations, which require continued ophthalmologic follow-up. New therapeutic strategies are therefore needed, particularly to target the ocular synthesis of the abnormal protein. PMID:26558262

  18. Evaluation of Therapeutic Oligonucleotides for Familial Amyloid Polyneuropathy in Patient-Derived Hepatocyte-Like Cells.

    PubMed

    Niemietz, Christoph J; Sauer, Vanessa; Stella, Jacqueline; Fleischhauer, Lutz; Chandhok, Gursimran; Guttmann, Sarah; Avsar, Yesim; Guo, Shuling; Ackermann, Elizabeth J; Gollob, Jared; Monia, Brett P; Zibert, Andree; Schmidt, Hartmut H-J

    2016-01-01

    Familial amyloid polyneuropathy (FAP) is caused by mutations of the transthyretin (TTR) gene, predominantly expressed in the liver. Two compounds that knockdown TTR, comprising a small interfering RNA (siRNA; ALN-TTR-02) and an antisense oligonucleotide (ASO; IONIS-TTRRx), are currently being evaluated in clinical trials. Since primary hepatocytes from FAP patients are rarely available for molecular analysis and commercial tissue culture cells or animal models lack the patient-specific genetic background, this study uses primary cells derived from urine of FAP patients. Urine-derived cells were reprogrammed to induced pluripotent stem cells (iPSCs) with high efficiency. Hepatocyte-like cells (HLCs) showing typical hepatic marker expression were obtained from iPSCs of the FAP patients. TTR mRNA expression of FAP HLCs almost reached levels measured in human hepatocytes. To assess TTR knockdown, siTTR1 and TTR-ASO were introduced to HLCs. A significant downregulation (>80%) of TTR mRNA was induced in the HLCs by both oligonucleotides. TTR protein present in the cell culture supernatant of HLCs was similarly downregulated. Gene expression of other hepatic markers was not affected by the therapeutic oligonucleotides. Our data indicate that urine cells (UCs) after reprogramming and hepatic differentiation represent excellent primary human target cells to assess the efficacy and specificity of novel compounds. PMID:27584576

  19. Genotype–phenotype correlation and course of transthyretin familial amyloid polyneuropathies in France

    PubMed Central

    Mariani, Louise‐Laure; Lozeron, Pierre; Théaudin, Marie; Mincheva, Zoia; Signate, Aissatou; Ducot, Beatrice; Algalarrondo, Vincent; Denier, Christian; Adam, Clovis; Nicolas, Guillaume; Samuel, Didier; Slama, Michel S.; Lacroix, Catherine; Misrahi, Micheline; Adams, David

    2015-01-01

    Objective To compare the natural history of familial transthyretin amyloid polyneuropathies (FAP) due to the Val30Met, Ser77Tyr, and Ile107Val mutations in France with the classical Portuguese Val30Met FAP. Methods We compared 84 French patients with a control group of 110 Portuguese patients carrying the Val30Met mutation also living in France, all referred to and followed at the French National FAP Reference Center from 1988 to 2010. Clinical examination, functional and walking disability scores, nerve conduction studies, and muscle biopsies are reported. We also conducted a comprehensive literature review to further determine the range of phenotypic expression. Results By comparison with Portuguese Val30Met FAP, French Ile107Val, Ser77Tyr, and LateVal30Met FAP showed more rapid and severe disease progression; onset of gait disorders was 3 times more rapid (p < 0.0001) and the rate of modified Norris test decline was up to 40 times faster in Ile107Val patients (p < 0.0001). Median survival was much shorter in Ile107Val and in Val30Met mutation with late onset (>50 years; LateMet30) FAP (p = 0.0005). Other distinctive features relative to the Portuguese patients included atypical clinical presentations, demyelination on nerve conduction studies (p = 0.0005), and difficult identification of amyloid deposits in nerve and muscle biopsies. Interpretation Ile107Val and LateMet30 mutations are associated with the most debilitating and severe FAP ever described, with rapid onset of tetraparesis and shorter median survival. It could be explained by frequent large‐fiber involvement and associated demyelination and more severe axonal loss. These findings have major implications for genetic counseling and patient management as new therapeutic options are being assessed in clinical trials (TTR gene silencing). Ann Neurol 2015;78:901–916 PMID:26369527

  20. Long-term effects of tafamidis for the treatment of transthyretin familial amyloid polyneuropathy.

    PubMed

    Coelho, Teresa; Maia, Luis F; da Silva, Ana Martins; Cruz, Márcia W; Planté-Bordeneuve, Violaine; Suhr, Ole B; Conceiçao, Isabel; Schmidt, Hartmut H-J; Trigo, Pedro; Kelly, Jeffery W; Labaudinière, Richard; Chan, Jason; Packman, Jeff; Grogan, Donna R

    2013-11-01

    Tafamidis, a transthyretin (TTR) kinetic stabilizer, delayed neuropathic progression in patients with Val30Met TTR familial amyloid polyneuropathy (TTR-FAP) in an 18-month randomized controlled trial (study Fx-005). This 12-month, open-label extension study evaluated the long-term safety, tolerability, and efficacy of tafamidis 20 mg once daily in 86 patients who earlier received blinded treatment with tafamidis or placebo. Efficacy measures included the Neuropathy Impairment Score in the Lower Limbs (NIS-LL), Norfolk Quality of Life-Diabetic Neuropathy total quality of life (TQOL) score, and changes in neurologic function and nutritional status. We quantified the monthly rates of change in efficacy measures, and TTR stabilization, and monitored adverse events (AEs). Patients who continued on tafamidis had stable rates of change in NIS-LL (from 0.08 to 0.11/month; p = 0.60) and TQOL (from -0.03 to 0.25; p = 0.16). In patients switched from placebo, the monthly rate of change in NIS-LL declined (from 0.34 to 0.16/month; p = 0.01), as did TQOL score (from 0.61 to -0.16; p < 0.001). Patients treated with tafamidis for 30 months had 55.9 % greater preservation of neurologic function as measured by the NIS-LL than patients in whom tafamidis was initiated later. Plasma TTR was stabilized in 94.1 % of patients treated with tafamidis for 30 months. AEs were similar between groups; no patients discontinued because of an AE. Long-term tafamidis was well tolerated, with the reduced rate of neurologic deterioration sustained over 30 months. Tafamidis also slowed neurologic impairment in patients previously given placebo, but treatment benefits were greater when tafamidis was begun earlier. PMID:23974642

  1. The Temporal Profiles of Changes in Nerve Excitability Indices in Familial Amyloid Polyneuropathy

    PubMed Central

    Lai, Hsing-Jung; Chiang, Ya-Wen; Yang, Chih-Chao; Hsieh, Sung-Tsang; Chao, Chi-Chao

    2015-01-01

    Familial amyloid polyneuropathy (FAP) caused by a mutation in transthyretin (TTR) gene is an autosomal dominant inherited disorder. The aim of this study is to explore the pathophysiological mechanism of FAP. We prospectively recruited 12 pauci-symptomatic carriers, 18 patients who harbor a TTR mutation, p.A97S, and two-age matched control groups. Data of nerve excitability test (NET) from ulnar motor and sensory axons were collected.NET study of ulnar motor axons of patients shows increased threshold and rheobase, reduced threshold elevation during hyperpolarizing threshold electrotonus (TE), and increased refractoriness. In sensory nerve studies, there are increased threshold reduction in depolarizing TE, lower slope of recovery and delayed time to overshoot after hyperpolarizing TE, increased refractoriness and superexcitability in recovery cycle. NET profiles obtained from the ulnar nerve of carriers show the increase of threshold and rheobase, whereas no significant threshold changes in hyperpolarizing TE and superexcitability. The regression models demonstrate that the increase of refractoriness and prolonged relative refractory period are correlated to the disease progression from carriers to patients. The marked increase of refractoriness at short-width stimulus suggests a defect in sodium current which may represent an early, pre-symptomatic pathophysiological change in TTR-FAP. Focal disruption of basal lamina and myelin may further increase the internodal capacity, manifested by the lower slope of recovery and delayed time to overshoot after hyperpolarization TE as well as the increase of superexcitability. NET could therefore make a pragmatic tool for monitoring disease progress from the very early stage of TTR-FAP. PMID:26529114

  2. Early identification of amyloid heart disease by technetium-99m-pyrophosphate scintigraphy: a study with familial amyloid polyneuropathy

    SciTech Connect

    Hongo, M.; Hirayama, J.; Fujii, T.; Yamada, H.; Okubo, S.; Kusama, S.; Ikeda, S.

    1987-03-01

    To determine whether technetium-99m-pyrophosphate (Tc-99m-PYP) scanning or two-dimensional echocardiography can detect amyloid heart disease in an earlier stage of familial amyloid polyneuropathy, 15 patients were examined. Although 10 of the 15 patients had no clinical evidence of congestive heart failure, as well as normal ventricular wall thickness and normal values for left ventricular systolic function, five (50%) of them showed mild or moderate myocardial uptake. On the other hand, none had characteristic highly refractile myocardial echoes on the two-dimensional echocardiographic images (p less than 0.01), and values for diastolic function were reduced in four of the five and normal in the remaining one. In 85 control subjects, diffuse positive pyrophosphate scans of the heart were found in four (5%) of them (three with dilated cardiomyopathy and one with sarcoidosis), and highly refractile granular sparkling echoes were observed in nine (11%) (five with hypertrophic cardiomyopathy, three with aortic stenosis, and one with hypereosinophilic syndrome). We conclude that Tc-99m-PYP scanning is a more sensitive and specific method and may have the potential ability to detect amyloid heart disease in the earlier stage of familial amyloid polyneuropathy than two-dimensional echocardiography.

  3. [Toxic polyneuropathies].

    PubMed

    Neundörfer, B

    1992-08-01

    Toxic factors may have damaging effects on the peripheral nerves at different sites: on the axon, on the myelin sheath, on the cell bodies and on the vasa nervorum. The toxic neuropathies can be divided up into polyneuropathies induced by drugs, by industrial, environmental and stimulant poisons. Mostly symmetrical sensory symptoms and signs are the first disturbances, often followed by symmetrical motor pareses. Some polyneuropathies induced by amiodarone, benzene, lead, cimetidine, chloroquine, dapsone, gentamycin, gold, imipramine, hexacarbons, nialamide, penicillin, triorthocresylphosphate and vincristine are primarily dominated by motory losses. Polyneuropathies induced by amitriptyline, ethylene, oxide, lead, chlorprothixene, heroin, hydralazine, methaqualone, nialamide and penicillin show an asymmetrical distribution pattern of the neural losses. In some types of toxic polyneuropathies the cranial nerves and the autonomic nerves are particularly involved. The clinical symptomatology of the most important types of toxic neuropathies are described shortly. The best therapy is, of course, termination of exposure to the toxic substance concerned. PMID:1509644

  4. Sensorimotor polyneuropathy

    MedlinePlus

    Neuropathy means a disease of, or damage to nerves. When it occurs outside of the brain or spinal cord, it is called a peripheral neuropathy. Mononeuropathy means one nerve is involved. Polyneuropathy means ...

  5. A case of familial amyloid polyneuropathy (FAP ATTR Ile107Val) with proximal muscle weakness in the lower extremities.

    PubMed

    Kuzume, Daisuke; Sajima, Kazuaki; Morimoto, Yuko; Komatsu, Kanako; Yamasaki, Masahiro; Enzan, Hideaki

    2016-04-28

    Proximal dominant muscle weakness is rare in transthyretin (TTR)-related familial amyloid polyneuropathy (FAP). A 69-year-old Japanese man developed numbness and dysesthesia of the first, second and third digits of both hands since 2008. He presented to our hospital with one year history of progressive proximal muscle weakness in the lower extremities since 2013. Neurological examinations revealed predominant proximal muscle weakness and atrophy with areflexia in the lower extremities, decreased superficial sensation in the first, second and third fingers of both hands, and decreased superficial and deep sensation in the lower extremities. Nerve conduction studies revealed an axonal degeneration type of sensorimotor polyneuropathy and bilateral carpal tunnel syndrome. Electromyogram revealed acute and chronic neurogenic changes predominantly in proximal muscles. We performed biopsy of the left quadriceps muscle and observed neurogenic changes in the muscle tissue and an amyloid deposition in the adipose tissue. This amyloid deposition was not seen in endomysium, perimysium and blood vessels. Genetic analysis of the TTR gene revealed the patient was heterozygous for a single nucleotide substitution c.379 A>G, which resulted in the replacement of valine with isoleucine at position 107 of the mature protein. We diagnosed his condition as FAP with Amyloid Transthyretin (ATTR) Ile107Val. PMID:27025994

  6. Liver transplantation and combined liver-heart transplantation in patients with familial amyloid polyneuropathy: a single-center experience.

    PubMed

    Barreiros, Ana-Paula; Post, Felix; Hoppe-Lotichius, Maria; Linke, Reinhold P; Vahl, Christian F; Schäfers, Hans-Joachim; Galle, Peter R; Otto, Gerd

    2010-03-01

    Liver transplantation (LT) is the only curative option for patients with familial amyloid polyneuropathy (FAP) at present. Twenty patients with FAP underwent LT between May 1998 and June 2007. Transthyretin mutations included predominantly the Val30Met mutation but also 10 other mutations. Seven patients received a pacemaker prior to LT, and because of impairment of mechanical cardiac function, 4 combined heart-liver transplants were performed, 1 simultaneously and 3 sequentially. The first patient, who underwent simultaneous transplantation, died. Seven patients died after LT, with 5 dying within the first year after transplantation. The causes of death were cardiac complications (4 patients), infections (2 patients), and malnutrition (1 patient). One-year survival was 75.0%, and 5-year survival was 64.2%. Gly47Glu and Leu12Pro mutations showed an aggressive clinical manifestation: 2 patients with the Gly47Glu mutation, the youngest patients of all the non-Val30Met patients, suffered from severe cardiac symptoms leading to death despite LT. Two siblings with the Leu12Pro mutation, who presented only with grand mal seizures, died after LT because of sepsis. In conclusion, the clinical course in patients with FAP is very variable. Cardiac symptoms occurred predominantly in patients with non-Val30Met mutations and prompted combined heart-liver transplantation in 4 patients. Although early LT in Val30Met is indicated in order to halt the typical symptoms of polyneuropathy, additional complications occurring predominantly with other mutations may prevail and lead to life-threatening complications or a fatal outcome. Combined heart-liver transplantation should be considered in patients with restrictive cardiomyopathy. PMID:20209591

  7. Variants in RBP4 and AR genes modulate age at onset in familial amyloid polyneuropathy (FAP ATTRV30M).

    PubMed

    Santos, Diana; Coelho, Teresa; Alves-Ferreira, Miguel; Sequeiros, Jorge; Mendonça, Denisa; Alonso, Isabel; Lemos, Carolina; Sousa, Alda

    2016-05-01

    Familial amyloid polyneuropathy (FAP) ATTRV30M is a neurodegenerative disorder due to point mutations in the transthyretin gene, with V30M being the commonest. FAP ATTRV30M shows a wide variation in age at onset (AO) between clusters, families and generations. Portuguese patients also show remarkable AO differences between genders. Genes found to be associated with FAP ATTRV30M pathways may act as AO modifiers. Our aim was to further explore the role of APCS and RBP4 genes and to study for the first time the involvement of sex-linked genetic modifiers - AR and HSD17B1 genes - in AO variation in Portuguese families. We collected DNA from a sample of 318 patients, currently under follow-up. A total of 18 tagging SNPs from APCS, RBP4, AR and HSD17B1 and 5 additional SNPs from APCS and RBP4 previously studied were genotyped. To account for nonindependency of AO between members of the same family, we used generalized estimating equations (GEEs). We found that APCS and RBP4 were associated with late AO. In addition, rs11187545 of the RBP4 was associated with an early AO. For the AR, in the male group three SNPs were associated with an early AO, whereas in the female group four were associated with both an early and later AO. These results strengthened the role of APCS and RBP4 genes and revealed for the first time the contribution of AR genes as an AO modifier in both males and females. These findings may have important implications in genetic counseling and for new therapeutic strategies. PMID:26286643

  8. Familial amyloid polyneuropathy associated with TTRSer50Arg mutation in two Iberian families presenting a novel single base change in the mutant gene.

    PubMed

    Munar-Qués, Miguel; Masjuan, Jaime; Coelho, Teresa; Moreira, Paul; Viader-Farré, Carlos; Saraiva, María J M

    2007-06-01

    We present two families, from Spain and Portugal, with familial amyloid polyneuropathy (FAP) associated with the mutation TTRSer50Arg. This mutation was first described in two Japanese patients from independent families and later in a French-Italian patient and a Vietnamese family. The two families presented here, are the first to be diagnosed with this mutation in the Iberian Peninsula. In the patients of both families, FAP was very aggressive as they rapidly developed multiple symptoms with progressive deterioration; we emphasize the presence of severe orthostatic hypotension in the Spanish proband which confined him to a wheelchair. This proband was the first patient with this mutation to have undergone liver transplantation and results were encouraging. The mutation was detected in four patients and one disease-free relative by DNA sequencing of exon 3 and induced mutation restriction analysis. The most outstanding feature was the single base transversion A to C in codon 50 (CGT instead of AGT), whereas in both Japanese patients and the French-Italian patient it was T to G (AGG instead of AGT). To our knowledge only six FAP mutations with more than one single nucleotide mutation for the same codon have been reported to date. PMID:17577688

  9. Chronic inflammatory polyneuropathy

    MedlinePlus

    ... nerves outside the brain or spinal cord ( peripheral neuropathy ). Polyneuropathy means several nerves are involved. It usually ... demyelinating polyneuropathy (CIDP) is the most common chronic neuropathy caused by an abnormal immune response. CIDP occurs ...

  10. Non-invasive assessment of the presence and severity of cardiac amyloidosis. A study in familial amyloidosis with polyneuropathy by cross sectional echocardiography and technetium-99m pyrophosphate scintigraphy.

    PubMed Central

    Eriksson, P; Backman, C; Bjerle, P; Eriksson, A; Holm, S; Olofsson, B O

    1984-01-01

    Twelve patients with familial amyloidosis with polyneuropathy were examined both by cross sectional echocardiography and by technetium-99m pyrophosphate scintigraphy to assess involvement of the heart non-invasively. All 12 patients had echocardiographic abnormalities. The most prominent findings were highly refractile myocardial echoes, thickened heart valves, and increased thickness of the heart walls. Four patients had abnormal myocardial uptake of technetium-99m pyrophosphate. The remaining eight had equivocal or no myocardial uptake and were considered to have normal scintigrams. A certain amount of amyloid is probably required to produce an abnormal scintigram, although lesions with less amyloid can evidently be identified by echocardiography. Neither the duration of polyneuropathy nor its severity showed any relation to the echocardiographic or scintigraphic findings. It is concluded that cross sectional echocardiography is superior to technetium-99m pyrophosphate scintigraphy in detecting cardiac involvement in familial amyloidosis with polyneuropathy and that these results may also be applicable to other forms of amyloidosis. Images PMID:6087862

  11. Polyneuropathy in juvenile dermatomyositis.

    PubMed

    Vogelgesang, S A; Gutierrez, J; Klipple, G L; Katona, I M

    1995-07-01

    We describe 2 patients in whom juvenile dermatomyositis (DM) was associated with well defined clinical polyneuropathies, and review the clinical and serological data. Light and electron microscopy were used to study muscle and nerve tissues from one patient. Neuropathy in our patients was associated with ulcerative skin lesions and elevated serum levels of factor VIII related antigen. Light microscopic studies of muscle revealed perifascicular atrophy and microinfarcts consistent with juvenile DM. Light microscopy of the affected sural nerve showed axonal degeneration. Electron microscopy of the same nerve demonstrated capillary endothelial inclusions characteristic of those observed as manifestations of early endothelial injury in juvenile DM muscle tissue. Polyneuropathy in patients with juvenile DM is a rare complication and is likely due to ischemia secondary to endothelial damage. PMID:7562774

  12. Chronic Inflammatory Demyelinating Polyneuropathy

    PubMed Central

    Dimachkie, Mazen M.; Barohn, Richard J.

    2014-01-01

    Opinion statement Chronic Inflammatory polyneuropathies are an important group of neuromuscular disorders that present chronically and progress over more than 8 weeks, being referred to as chronic inflammatory demyelinating polyneuropathy (CIDP). Despite tremendous progress in elucidating disease pathogenesis, the exact triggering event remains unknown. Our knowledge regarding diagnosis and management of CIDP and its variants continues to expand, resulting in improved opportunities for identification and treatment. Most clinical neurologists will be involved in the management of patients with these disorders, and should be familiar with available therapies for CIDP. We review the distinctive clinical, laboratory, and electro-diagnostic features that aid in diagnosis. We emphasize the importance of clinical patterns that define treatment responsiveness and the most appropriate therapies in order to improve prognosis. PMID:23564314

  13. [Noninvasive diagnosis of cardiac involvement by technetium-99m-pyrophosphate (Tc-99m PYP) myocardial scintigraphy in 2 cases of familial amyloid polyneuropathy and 1 case of secondary amyloidosis].

    PubMed

    Takezaki, M; Ishida, Y; Morozumi, T; Tani, A; Sato, H; Hori, M; Kitabatake, A; Kamada, T; Kimura, K; Kozuka, T

    1989-12-01

    To validate the significance of technetium-99m-pyrophosphate (Tc-99m PYP) myocardial scintigraphy in diagnosing cardiac amyloidosis, 2 patients with familial amyloid polyneuropathy (FAP) and 1 patient with amyloidosis secondary to chronic rheumatic arthritis were studied. All three patients had echocardiographic abnormalities, which were increased wall thickness of the interventricular septum and the left ventricular posterior wall, and granular sparkling appearance in the septum. In 2 patients with FAP, abnormal myocardial uptake of Tc-99m PYP was diffusely detected in Tc-99m PYP SPECT. In the remaining 1 patient with secondary amyloidosis, however, Tc-99m PYP SPECT showed no abnormality, although we had confirmed the presence of myocardial amyloid deposits (type AA amyloid protein) with high amount in the histological examination. Thus, these results indicate that Tc-99m PYP scintigraphy may have a limitation in detecting cardiac involvement in secondary amyloidosis although it is useful in FAP. PMID:2560088

  14. CRYPTOGENIC SENSORY POLYNEUROPATHY

    PubMed Central

    Pasnoor, Mamatha; Dimachkie, Mazen M.; Barohn, Richard J.

    2014-01-01

    Chronic sensory or sensorimotor polyneuropathy is a common cause for referral to neurologists. Despite extensive diagnostic testing, up to one-third of these patients remain without a known cause. They are referred to as having cryptogenic sensory peripheral neuropathy (CSPN). The age of onset is variable but usually in the sixth to seventh decade of life, affecting men and women equally. CSPN symptoms progress slowly, most patients present with distal leg paresthesias or pain that progressed over years to involve the hands. On examination, there may be additional mild toe flexion and extension weakness. Electrophysiologic testing and histology reveals axonal neuropathy. Prognosis is usually favorable as most patients maintain independent ambulation. Besides patient education and reassurance, management is focused on pharmacotherapy of neuropathic pain (see Treatment of Painful Peripheral Neuropathy chapter) and physical therapy for balance training and occasionally assistive devices. PMID:23642719

  15. Subclinical Inflammation and Diabetic Polyneuropathy

    PubMed Central

    Herder, Christian; Lankisch, Mark; Ziegler, Dan; Rathmann, Wolfgang; Koenig, Wolfgang; Illig, Thomas; Döring, Angela; Thorand, Barbara; Holle, Rolf; Giani, Guido; Martin, Stephan; Meisinger, Christa

    2009-01-01

    OBJECTIVE Subclinical inflammation represents a risk factor of type 2 diabetes and several diabetes complications, but data on diabetic neuropathies are scarce. Therefore, we investigated whether circulating concentrations of acute-phase proteins, cytokines, and chemokines differ among diabetic patients with or without diabetic polyneuropathy. RESEARCH DESIGN AND METHODS We measured 10 markers of subclinical inflammation in 227 type 2 diabetic patients with diabetic polyneuropathy who participated in the population-based MONICA/KORA Survey F3 (2004–2005; Augsburg, Germany). Diabetic polyneuropathy was diagnosed using the Michigan Neuropathy Screening Instrument (MNSI). RESULTS After adjustment for multiple confounders, high levels of C-reactive protein and interleukin (IL)-6 were most consistently associated with diabetic polyneuropathy, high MNSI score, and specific neuropathic deficits, whereas some inverse associations were seen for IL-18. CONCLUSIONS This study shows that subclinical inflammation is associated with diabetic polyneuropathy and neuropathic impairments. This association appears rather specific because only certain immune mediators and impairments are involved. PMID:19131463

  16. Chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Mathey, Emily K; Pollard, John D

    2013-10-15

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is the commonest treatable neuropathy in the western world. Untreated it may result in severe disability but if diagnosed and treated early there is effective treatment for the majority of patients. Typical CIDP is readily recognised but the diagnosis of other subgroups can be more challenging. The pathology of polyradiculoneuropathies such as CIDP characteristically affects the most proximal regions of the peripheral nervous system, nerve roots and major plexuses. It is important to test these regions with electrodiagnostic studies since routine neurophysiology may not encounter regions of pathology. Although accepted as an autoimmune disorder with an underlying immunopathology involving T cell and B cell responses, there is no agreement on major target antigens; however recent studies have highlighted a role for molecules in non compact myelin which play an essential role in the formation and maintenance of the nodal structures and hence in the function of ion channels central to saltatory conduction. Controlled trials have proven the efficacy of corticosteroid, intravenous immunoglobulin and plasma exchange in the short term and intravenous immunoglobulin also in the long term. Immunosuppressive agents are widely used but their efficacy has not been proven in controlled trials. Recent trials have shown the importance of attempting treatment withdrawal in patients apparently in remission to conserve treatments that are very expensive and in short supply, since a significant proportion of patients may enter long lasting remission following short term therapy. For the relatively small group of patients who do not respond to these first line therapies new agents including monoclonal antibodies may have a role. PMID:23146613

  17. Dysautonomic polyneuropathy as a variant of chronic inflammatory "demyelinating" polyneuropathy?

    PubMed

    Wolf, Hans-Heinrich; Kornhuber, Malte Erich; Weis, Joachim; Posa, Andreas

    2016-08-01

    This report describes the clinical course over almost one decade of a male patient presenting with immune-mediated pure autonomic neuropathy resembling a distinct variant of chronic dysimmune polyneuropathies. We suppose autoantibodies directed against epitopes on autonomic axons or neurons causative for the symptoms. PMID:27379500

  18. Sixty years of transthyretin familial amyloid polyneuropathy (TTR-FAP) in Europe: where are we now? A European network approach to defining the epidemiology and management patterns for TTR-FAP

    PubMed Central

    Parman, Yesim; Adams, David; Obici, Laura; Galán, Lucía; Guergueltcheva, Velina; Suhr, Ole B.; Coelho, Teresa

    2016-01-01

    Purpose of review Transthyretin familial amyloid polyneuropathy (TTR-FAP) is a highly disabling, life-threatening disease characterized by progressive sensorimotor and autonomic neuropathy. The profile of the disease across Europe is inadequately understood at present. Recent findings The incidence and clinical presentation of TTR-FAP varies widely within Europe, with early and late-onset disease subtypes. In those regions in which the disease is endemic (Portugal, Sweden, Cyprus, and Majorca), a Val30Met substitution in the TTR gene is the predominant genetic cause, whereas in the rest of Europe, cases of TTR-FAP are mainly sporadic with genetic heterogeneity. Current management strategies lack cohesion and patients can experience years of misdiagnosis and suboptimal treatment. Summary The article aims to disseminate the findings and recommendations from two recent meetings of the European Network for TTR-FAP (ATTReuNET), a panel comprising representatives from 10 European countries (Bulgaria, Cyprus, France, Germany, Italy, the Netherlands, Portugal, Spain, Sweden, and Turkey) with expertise in the diagnosis and management of TTR-FAP. We explore the epidemiology and genetic mark of TTR-FAP across Europe and assess current management strategies, with a view to developing an alternative framework – a networked approach to disease management with an emphasis on collaboration and sharing of best practice. PMID:26734951

  19. [Pain therapy in HIV-associated polyneuropathy].

    PubMed

    Husstedt, I W; Böckenholt, S; Kammer-Suhr, B; Evers, S

    2001-04-01

    Only some patients with HIV-infection receive an adequate pain therapy. In later stages of HIV-infection up to 50% 6 of patients perform extraordinary doctor visits because of pain. Principally primary and secondary neuromanifestations of HIV-infection have to be differentiated. Rare forms of HIV-associated polyneuropathies represent mononeuropathy or mononeuritis multiple acute and chronic inflammatory demyelinating polyneuropathy and polyneuropathy caused by opportunistic infections. HIV-associated distal-symmetric polyneuropathy represents the most common form during HIV-infection with a prevalence up to 50%. Typical clinical symptoms and signs are pain, hyp- and dysaesthesia, diminuted deep tendon reflexes, motor deficits and autonomic disturbances. Always neurological examination and neurophysiologic investigation on the sural and peronaeal nerve are necessary for monitoring progression of polyneuropathy and as basics before starting antiretroviral therapy with neurotoxic substances. According to momentary opinion, HIV-associated distal-symmetric polyneuropathy represents no indication for antiretroviral therapy. Symptomatic therapy includes antiepileptic medication as gabapentine, antidepressive drugs as amitiptyline and additionally retarded opiates. Depressive disorders ma y accentuate pain problems a n d need psychotherapeutic and thymoleptic therapy. Special problems occur when neurotoxic substances evoke or deteriorate polyneuropathy. In these cases an individual therapeutic proceeding about continuation or discontinuation of neurotoxic medication is necessary. Symptoms of myopathy during HIV-infection are muscle pain, elevation of CK and typical changes of motor units detected by electromyography. In most cases biopsy is necessary for diagnosis of specific forms of HN-associated myopathy. HIV-associated polymyositis is treated by non-steroid analgetics, corticoids, immunoglobulines and plasmapheresis, myopathy induced by neurotoxic medication analogous

  20. Could Spinal Canal Compression be a Cause of Polyneuropathy?

    PubMed Central

    Bostelmann, Richard; Zella, Samis; Steiger, Hans Jakob; Petridis, Athanasios K.

    2016-01-01

    Causality between spinal cord compression and polyneuropathy is difficult to define, especially under the circumstances that polyneuropathy can have many causes. Seven patients with spinal cord compression and electrophysiological signs of polyneuropathy were treated surgically on decompression of their spinal canal stenosis in the time from April 2010 to January 2013. Median follow up time was 9 months (2-23 months). Causes of polyneuropathy were: 1 patient with methotrexate-induced polyneuropathy, 1 endocrine-dysfunction-induced, 2 with diabetic-polyneuropathy, and 3 patients had unknown reasons. The localization of the spinal canal stenosis was also varying: 2 patients suffered of cervical spinal canal stenosis and 5 of lumbar. Decompressive surgery led to pain relieve in all patients initially. Surprisingly, also symptoms of polyneuropathy seemed to regress in all 7 patients for the first 5 months after surgery, and in 5 patients for the time of 9 months after surgery. There are two points we would like to emphasize in this short report. Since 5/7 patients with polyneuropathy and spinal canal stenosis improved clinically after surgery, surgery has a place in the treatment of such a combined pathology. Since it seems to be a possible causality between polyneuropathy of unknown origin and spinal cord stenosis, decompression of the spinal canal could also be a therapeutic step in a specific kind of polyneuropathy. Which patients could possibly have a spinal canal stenosis induced polyneuropathy remains a subject of further studies. PMID:27162603

  1. Pathological features of polyneuropathy in three dogs.

    PubMed

    Tsuboi, Masaya; Uchida, Kazuyuki; Ide, Tetsuya; Ogawa, Mizue; Inagaki, Takehiko; Tamura, Shinji; Saito, Miyoko; Chambers, James K; Nakayama, Hiroyuki

    2013-01-01

    Canine polyneuropathy is a neurological disorder characterized by a dysfunction of multiple peripheral nerves. The etiology of the disease is diverse; it may occur in cases of infectious, immune-mediated, or hereditary conditions or in association with endocrinopathy, neoplasm, or chemical intoxication. It is often difficult to determine the etiology through clinical symptoms. The aim of this study is to investigate pathological differences among three canine polyneuropathy cases with each presumably having a different etiology. Cases included a 13-month-old female border collie (Dog No.1), a 21-month-old male chihuahua (Dog No.2) and an 11-year-old male beagle (Dog No.3). Clinical examinations revealed hindlimb ataxia and sensory loss in Dog No.1, forelimb paralysis and vertebral pain in Dog No.2, and paddling-gait and hypothyroidism in Dog No.3. Histopathologically, axonal swelling and pale myelin were observed in Dog No.1. Giant axons mimicking giant axonal neuropathy were obvious in Dog No.2. Dog No.3 showed atrophic axons and severe interstitial edema. Distributions of peripheral nerve lesions coincided with respective clinical symptoms. According to their clinical and pathological features, Dogs No.1 and No.2 were suspected of hereditary polyneuropathy, while Dog No.3 seemed to have hypothyroidism-associated polyneuropathy. As each case demonstrated unique pathological features, different pathogeneses of peripheral nerve dysfunction were suggested. PMID:23123885

  2. Erythropoietin and polyneuropathy in older persons

    PubMed Central

    Lauretani, Fulvio; Bandinelli, Stefania; Strotmeyer, Elsa S.; Corsi, Anna Maria; Di Iorio, Angelo; Guralnik, Jack M.; Ferrucci, Luigi

    2016-01-01

    Introduction Recent studies demonstrated that erythropoietin (EPO) have a number of non-erythropoietic effects including neuroprotection and vascular protection. Materials Using data from a representative sample of older persons, we tested the hypothesis that EPO levels are correlated with peripheral nerve parameters (NVC and CMAP) assessed by surface ENG and with clinically diagnosed polyneuropathy. We selected 972 participants (aged 60–98 years) with complete data for the analyses. Results We found a significant association between EPO and age-adjusted NCV and CMAP (for NCV: 0.57 ± 0.26; p = 0.03 and for CMAP: 0.54 ± 0.23; p = 0.02). In logistic regression models adjusting for age, sex and multiple potential confounders, higher EPO levels were associated with a significantly lower probability of having a clinical diagnosis of polyneuropathy (OR = 0.43; 95% CI: 0.22–0.84). Discussion These findings suggest that EPO is implicated in the pathogenesis of polyneuropathy in older persons. Whether low EPO is a risk factor for polyneuropathy should be tested in future longitudinal analyses. PMID:18439654

  3. Polyneuropathy induced by carbon disulphide in viscose rayon workers.

    PubMed Central

    Chu, C C; Huang, C C; Chen, R S; Shih, T S

    1995-01-01

    OBJECTIVES--To understand the prevalence of polyneuropathy and correlations among the clinical manifestations, electrophysiological findings, and degree of exposure to carbon disulphide (CS2) in workers who were exposed to variable concentrations of CS2 in a viscose rayon factory. METHODS--All the 163 workers received a detailed physical and neurological evaluation. Fixed point air samples were analysed for CS2. Nerve conduction velocity was studied in 26 workers with symptoms similar to neuropathy. RESULTS--Nine workers (53%) with overt polyneuropathy from the fibre cutting department and 19 workers (13%) with oligosymptoms similar to polyneuropathy from various jobs were noted. The fixed point air concentrations of CS2 were 150-300 ppm in the cutting areas and 15 to 100 ppm in the spinning areas. The estimated eight hour time weighted averages in the fibre cutting areas were 40-67 ppm. The occurrence of polyneuropathy was generally correlated with the degree of exposure to CS2. Nerve conduction velocities (NCVs) were significantly different in the overt polyneuropathy and subclinical polyneuropathy groups from the normal controls. The sensitive indicators for CS2 polyneuropathy were distal latency, motor NCV, and amplitude of sensory nerve action potentials in sensory NCVs. CONCLUSION--The outbreak of polyneuropathy was attributed to higher concentrations of CS2 in fibre cutting areas. Even in other jobs with relatively lower concentrations of CS2, the hazard of subclinical polyneuropathy cannot be overlooked. PMID:7627318

  4. Acute idiopathic polyneuropathy in the dog.

    PubMed

    Northington, J W; Brown, M J; Farnbach, G C; Steinberg, S A

    1981-08-15

    From among a large group of dogs with acute tetraparesis, we identified 10 dogs with a distinct peripheral nerve disorder. Prior to the onset of signs, all of the dogs had been healthy, and none was known to have been exposed to a neurotoxin or raccoon bite. Weakness, with hypoactive or absent segmental reflexes, became progressively worse for 1 to 21 days. Results of electromyography and nerve conduction studies invariably were compatible with a diagnosis of polyneuropathy that predominantly affected proximal nerve segments. Appearance of nerve biopsy specimens and the short time course for functional recovery suggested a demyelinative component to the disorder. The extent of recovery was variable but often rapid and complete in dogs that did not succumb to complications in the early period. Corticosteroid therapy did not demonstrably influence the outcome. This acute idiopathic polyneuropathy in the dog shares many clinical and pathologic features with idiopathic polyradiculoneuritis (Coonhound paralysis). PMID:6270046

  5. [Polyneuropathy associated with monoclonal gammapathy: treatment perspectives].

    PubMed

    Leger, Jean-Marc; Chassande, Bénédicte; Bombelli, Francesco; Viala, Karine; Musset, Lucile; Neil, Jean

    2009-05-01

    Since the first report of a high prevalence of monoclonal gammapathy (MG) in patients with peripheral neuropathy (PN), some 25 years ago, a large number of such associations have been described. Neuropathies associated with MG have heterogeneous clinical, neurophysiological, neuropathological, and hematological features. The most pertinent relationship seems to be that between distal acquired demyelinating sensory (DADS) neuropathy associated with IgM MG of unknown significance (MGUS) and the presence of serum autoantibodies reacting with myelin-associated glycoprotein (MAG). Other interesting correlations were recently reported in CANOMAD (chronic ataxic neuropathy with ophthalmoplegia, M-protein and anti-disialosyl antibodies). Patients with demyelinating neuropathy (DNP) associated with MG should be screened for malignant plasma cell dyscrasia. MG is more likely to be responsible for the neuropathy if it consists of IgM, if autoantibodies (mainly directed to MAG) are found in serum or on nerve biopsy, and if the clinical manifestations correspond to chronic distal sensory neuropathy. DNP associated with IgM MGUS sometimes responds to immunotherapy but the potential benefits must be considered in view of possible adverse effects. Rituximab, an anti-CD20 monoclonal antibody, has shown promise in this setting. DNP associated with IgG or IgA MGUS may be indistinguishable from chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), in terms of clinical and electrophysiological features and the treatment response. In the POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes), appropriate treatment can lead to a drastic improvement in the neuropathy. Patients with chronic axonal polyneuropathy associated with IgG MG should be screened for Al amyloidosis. However, most axonal polyneuropathies associated with IgG or IgM MGUS are indistinguishable from chronic idiopathic axonal polyneuropathies. PMID:20120390

  6. Antiarrhythmic drugs and polyneuropathy. The Collaborative Group for the Study of Polyneuropathy.

    PubMed Central

    1994-01-01

    A total of 151 patients on chronic treatment with amiodarone and other antiarrhythmic drugs were subjected to standard clinical and electrophysiological investigation to assess the prevalence and specificity of polyneuropathy. Twenty two untreated patients with cardiac disorders and 246 normal subjects served as controls. Abnormal electrophysiological findings supporting the diagnosis of polyneuropathy were present in 38 subjects (25%) given antiarrhythmic drugs, with even distribution among drugs, and four untreated patients (18%). Concurrent clinical abnormalities were present in five treated patients (one each with amiodarone, propafenone, and flecainide, and two with multiple drugs). Therefore, electrophysiological abnormalities are a common, although non-specific, feature in patients taking antiarrhythmic drugs. Amiodarone users do not seem at higher risk of polyneuropathy than subjects treated with other drugs or even untreated patients with cardiac disorders. PMID:8158183

  7. Ultrasound of Inherited vs. Acquired Demyelinating Polyneuropathies

    PubMed Central

    Zaidman, Craig M.; Harms, Matthew B.; Pestronk, Alan

    2013-01-01

    Introduction We compared features of nerve enlargement in inherited and acquired demyelinating neuropathies using ultrasound. Methods We measured median and ulnar nerve cross-sectional areas in proximal and distal regions in 128 children and adults with inherited (Charcot-Marie Tooth-1 (CMT-1) (n=35)) and acquired (Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) (n=55), Guillaine-Barre Syndrome (GBS) (n=21) and Multifocal Motor Neuropathy (MMN) (n=17)) demyelinating neuropathies. We classified nerve enlargement by degree and number of regions affected. We defined patterns of nerve enlargement as: none- no enlargement; mild-nerves enlarged but never more than twice normal; regional- nerves normal at at least one region and enlarged more than twice normal at atleast one region; diffuse- nerves enlarged at all four regions with atleast one region more than twice normal size. Results Nerve enlargement was commonly diffuse (89%) and generally more than twice normal size in CMT-1, but not (p<0.001) in acquired disorders which mostly had either no, mild or regional nerve enlargement (CIDP (64%), GBS (95%), and MMN (100%)). In CIDP, subjects treated within three months of disease onset had less nerve enlargement than those treated later. Discussion Ultrasound identified patterns of diffuse nerve enlargement can be used to screen patients suspected of having CMT-1. Normal, mildly, or regionally enlarged nerves in demyelinating polyneuropathy suggests an acquired etiology. Early treatment in CIDP may impede nerve enlargement. PMID:24101129

  8. My legs are getting old: sinvastatin-induced polyneuropathy

    PubMed Central

    Camargos, Einstein Francisco; de Freitas Oliveira, Larissa; Boaventura, Thaís de Deus Vieira

    2011-01-01

    Axonal degeneration is the most common type of neuropathy induced by medication. The literature describes isolated cases in which polyneuropathy of the lower limb was observed during treatment with statins. The authors present a case of polyneuropathy associated with the use of a statin. An 82-year-old female patient presented with a complaint of weakness and discomfort in her lower limbs after 7 years of therapy with simvastatin. The results of an electromyographic study were compatible with polyneuropathy (sensorimotor axonal neuropathy – moderate to severe). One month after the therapy with simvastatin was discontinued, the symptoms were reduced. PMID:22707627

  9. Whither pathogenetic treatments for diabetic polyneuropathy?

    PubMed

    Boulton, Andrew J M; Kempler, Peter; Ametov, Alexander; Ziegler, Dan

    2013-07-01

    Diabetic distal symmetric polyneuropathy (DSPN) occurs in around one-third of patients with diabetes and is associated with significant morbidity and increased mortality. Diagnosis and clinical assessment of DSPN remain a challenge, not only for the physician in clinical practice but also for clinical trials. Optimal diabetes control is generally considered an essential first step in the prevention and management of DSPN. However, glycaemic control alone may be insufficient to prevent the development or progression of DSPN, especially in type 2 diabetes. Near-normoglycaemia is also difficult to achieve in a significant proportion of patients. Although considerable advances have been made in symptomatic pain management, these have not addressed the problem of sensory deficits and have no impact on the underlying pathogenesis of DSPN. There remains a lack of treatment options that effectively target the natural history of the disease. Several pathogenetic treatment approaches have been investigated, but evidence from clinical trials is limited with a number of treatments having shown disappointing results. However, some pathogenetic therapies have shown clinically relevant improvements in neuropathic endpoints in randomised controlled trials, in particular α-lipoic acid and Actovegin. These advances in DSPN disease modification need to be confirmed with further robust evidence from clinical trials together with a better understanding of the mechanisms of action of promising treatments. PMID:23381942

  10. Treatment of diabetic polyneuropathy: Update 2006.

    PubMed

    Ziegler, Dan

    2006-11-01

    At least one of four diabetic patients is affected by distal symmetric polyneuropathy (DSP), which represents a major health problem, as it may present with partly excruciating neuropathic pain and is responsible for substantial morbidity, increased mortality, and impaired quality of life. Treatment is based on four cornerstones: (a) causal treatment aimed at (near)-normoglycemia, (b) treatment based on pathogenetic mechanisms, (c) symptomatic treatment, and (d) avoidance of risk factors and complications. Recent experimental studies suggest a multifactorial pathogenesis of diabetic neuropathy. From the clinical point of view it is important to note that, on the basis of these pathogenetic mechanisms, therapeutic approaches could be derived, some of which are currently being evaluated in clinical trials. Among these agents only alpha-lipoic acid is available for treatment in several countries and epalrestat in Japan. Although several novel analgesic drugs, such as duloxetine and pregabalin, have recently been introduced into clinical practice, the pharmacological treatment of chronic painful diabetic neuropathy remains a challenge for the physician. Individual tolerability remains a major aspect in any treatment decision. Epidemiological data indicate that not only increased alcohol consumption but also the traditional cardiovascular risk factors, such as hypertension, smoking, and visceral obesity, play a role in development and progression of diabetic neuropathy and, hence, need to be prevented or treated. PMID:17151306

  11. The treatment of inflammatory polyneuropathy by plasma exchange.

    PubMed Central

    Gross, M L; Legg, N J; Lockwood, M C; Pallis, C

    1982-01-01

    Observations are reported on six patients with inflammatory polyneuropathy who were treated by plasma exchange. In four cases the polyneuropathy was acute and in two it was chronic or relapsing. Two acute cases and one chronic relapsing case had plasma exchange during a rapidly progressive phase of the disease, and showed a prompt and substantial recovery of function. The other three patients were exchanged when disease activity had reached a plateau. Only minor degrees of improvement were seen in two of these cases. One patient showed an initial mild deterioration before subsequent recovery. There were no significant side effects. These findings are discussed in relation to the pathogenesis and clinical management of inflammatory polyneuropathy. PMID:7130991

  12. n-Hexane polyneuropathy in a ball-manufacturing factory

    SciTech Connect

    Huang, C.C.; Shih, T.S.; Cheng, S.Y.; Chen, S.S.; Tchen, P.H. )

    1991-02-01

    Five overt and two occult cases of n-hexane polyneuropathy occurred in a ball-manufacturing factory in Taiwan. The severity of polyneuropathy was directly related to the index of n-hexane exposure that occurred during the processes of cement coating and nylon fiber winding in a poorly ventilated room. The n-hexane concentrations over eight hours of personal sampling of the air of the cement coating and nylon fiber winding areas were 109 ppm and 86 ppm, respectively. After installation of a new factory ventilation system, these seven patients recovered completely, and there were no new cases in the two-year follow-up.

  13. [A syndrome of chronic ataxic polyneuropathy, ophtalmoplegia, IgM paraprotein, cold agglutinins and anti-disialosyl antibodies can cause diplopia in patients with chronic sensory polyneuropathy].

    PubMed

    Kolmos, Eva Brøsted; Moth Henriksen, Marie; Abildgaard, Niels; Sindrup, Søren Hein

    2012-10-22

    CANOMAD is a rare syndrome of chronic ataxic polyneuropathy, ophtalmoplegia, IgM paraprotein, cold agglutinins and anti-disialosyl antibodies. We present a case of a 65-year-old woman with clinical and electrophysiological features of chronic sensory polyneuropathy and diplopia. Serum samples from the patient contained IgM paraprotein and anti-GM2-antibodies. Treatment with intravenous immunoglobulins resulted in an improvement of the patient's diplopia and polyneuropathy. The case shows the importance of considering CANOMAD as a cause of diplopia in patients with chronic sensory polyneuropathy. PMID:23095653

  14. Charcot-Marie-Tooth (CMT) disease 1A with superimposed inflammatory polyneuropathy in children.

    PubMed

    Desurkar, A; Lin, J-P; Mills, K; Al-Sarraj, S; Jan, W; Jungbluth, H; Wraige, E

    2009-04-01

    Charcot-Marie-Tooth (CMT) disease is genetically heterogeneous and subdivided into demyelinating (CMT 1) and axonal (CMT 2) types based on neurophysiology findings. CMT1A, the commonest form associated with duplication of the PMP22 segment on chromosome 17p, often arises in childhood but is generally a slowly progressive disease. We report 2 children presenting with clinical features of an acute inflammatory demyelinating polyneuropathy (AIDP) who were subsequently diagnosed with underlying CMT1A. Both children had neurophysiology and histopathology features consistent with CMT1. Immunoglobulin treatment was initiated considering the evidence of superimposed inflammation and appeared to modify disease progression. Our findings indicate that CMT1A predisposes to a superimposed inflammatory neuropathy. Recognition of this association is difficult, particularly in children without clear family history, but of great importance as immunomodulatory treatment may improve outcome. In addition, we postulate that an underlying genetic polyneuropathy should be suspected if the recovery from AIDP is slower than expected, or incomplete. PMID:19809938

  15. [A MODERN APPROACH TO THE TREATMENT OF DIABETIC POLYNEUROPATHY].

    PubMed

    Romanova, I P; Kazakov, A V; Oleynikova, S P; Chernyavskaya, I V; Dorosh, E G

    2015-01-01

    In this paper, the authors conducted research on the application of a new drug for the treatment of diabetic polyneuropathy in patients with diabetes mellitus type 1 and 2. Established an effective influence on the hemodynamic, metabolic, biochemical parameters, improved sensory-motor conduction in nerve fibers. Recommended for widespread use in patients with diabetes mellitus. PMID:27491158

  16. MNGIE neuropathy: five cases mimicking chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Bedlack, Richard S; Vu, Tuan; Hammans, Simon; Sparr, Steven A; Myers, Bennett; Morgenlander, Joel; Hirano, Michio

    2004-03-01

    We report five patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) who had demyelinating peripheral neuropathy. The MNGIE neuropathy had clinical and electrodiagnostic features typical of acquired, rather than inherited, etiologies. In fact, three patients were actually treated for chronic inflammatory demyelinating polyneuropathy (CIDP). We discuss findings that may help distinguish patients with MNGIE from those with CIDP. PMID:14981734

  17. Syndrome of polyneuropathy, skin hyperpigmentation, oedema and hepatosplenomegaly.

    PubMed Central

    Tang, L M; Hsi, M S; Ryu, S J; Minauchi, Y

    1983-01-01

    Four middle-aged male Chinese with polyneuropathy, skin hyperpigmentation, oedema, hepatosplenomegaly, ascites, gynaecomastia and white nails are described. In Japan and United States this syndrome has been associated with plasma cell dyscrasia. However, neither M-protein nor skeletal lesions were demonstrated in these four patients. Images PMID:6663309

  18. Acute Onset Sensory Polyneuropathy Due to Metronidazole Therapy.

    PubMed

    Singh, Jitendra; Atam, Virendra; Dinkar, Anju

    2015-09-01

    Metronidazole is associated with numerous neurologic complications, including peripheral neuropathy particularly in patients; those are on high doses of metronidazole for prolonged period. We hereby report a case of liver abscess that developed sensory polyneuropathy following 11 days of metronidazole therapy at low cumulative dose. PMID:27608880

  19. Nerve excitability changes in critical illness polyneuropathy.

    PubMed

    Z'Graggen, W J; Lin, C S Y; Howard, R S; Beale, R J; Bostock, H

    2006-09-01

    Patients in intensive care units frequently suffer muscle weakness and atrophy due to critical illness polyneuropathy (CIP), an axonal neuropathy associated with systemic inflammatory response syndrome and multiple organ failure. CIP is a frequent and serious complication of intensive care that delays weaning from mechanical ventilation and increases mortality. The pathogenesis of CIP is not well understood and no specific therapy is available. The aim of this project was to use nerve excitability testing to investigate the changes in axonal membrane properties occurring in CIP. Ten patients (aged 37-76 years; 7 males, 3 females) were studied with electrophysiologically proven CIP. The median nerve was stimulated at the wrist and compound action potentials were recorded from abductor pollicis brevis muscle. Strength-duration time constant, threshold electrotonus, current-threshold relationship and recovery cycle (refractoriness, superexcitability and late subexcitability) were recorded using a recently described protocol. In eight patients a follow-up investigation was performed. All patients underwent clinical examination and laboratory investigations. Compared with age-matched normal controls (20 subjects; aged 38-79 years; 7 males, 13 females), CIP patients exhibited reduced superexcitability at 7 ms, from -22.3 +/- 1.6% to -7.6 +/- 3.1% (mean +/- SE, P approximately 0.0001) and increased accommodation to depolarizing (P < 0.01) and hyperpolarizing currents (P < 0.01), indicating membrane depolarization. Superexcitability was reduced both in patients with renal failure and without renal failure. In the former, superexcitability correlated with serum potassium (R = 0.88), and late subexcitability was also reduced (as also occurs owing to hyperkalaemia in patients with chronic renal failure). In patients without renal failure, late subexcitability was normal, and the signs of membrane depolarization correlated with raised serum bicarbonate and base excess

  20. Fibrillary glomerulonephritis combined with chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Sung, Woo Kyung; Jeong, Jin Uk; Bang, Ki Tae; Shin, Jong Ho; Yoo, Ji Hyung; Kim, Nak Min; Park, Jun Hyung; Kim, Joo Heon

    2015-06-01

    A 58-yr-old man presented with leg edema and subacute weakness of his bilateral lower extremities. Urinary and serum immunoelectrophoresis revealed the presence of lambda-type Bence Jones proteins. He was ultimately diagnosed with monoclonal gammopathy of undetermined significance (MGUS). A renal biopsy specimen showed fibrillary glomerulonephritis (FGN), which was randomly arranged as 12-20 m nonbranching fibrils in the basement membranes. Immunofluorescence studies were negative for immunoglobulin (Ig)G, IgM, IgA, C3, and kappa light chains in the capillary walls and mesangial areas. A Congo red stain for amyloid was negative. Electromyography and nerve conduction velocity examinations results were compatible with the presence of demyelinating polyneuropathy. This case showed a rare combination of FGN, without Ig deposition, and MGUS combined with chronic inflammatory demyelinating polyneuropathy (CIDP). PMID:26484033

  1. Bilateral Diaphragmatic Paralysis in a Patient With Critical Illness Polyneuropathy

    PubMed Central

    Chen, Hsuan-Yu; Chen, Hung-Chen; Lin, Meng-Chih; Liaw, Mei-Yun

    2015-01-01

    Abstract Bilateral diaphragmatic paralysis (BDP) manifests as respiratory muscle weakness, and its association with critical illness polyneuropathy (CIP) was rarely reported. Here, we present a patient with BDP related to CIP, who successfully avoided tracheostomy after diagnosis and management. A 71-year-old male presented with acute respiratory failure after sepsis adequately treated. Repeated intubation occurred because of carbon dioxide retention after each extubation. After eliminating possible factors, septic shock-induced respiratory muscle weakness was suspected. Physical examination, a nerve conduction study, and chest ultrasound confirmed our impression. Pulmonary rehabilitation and reconditioning exercises were arranged, and the patient was discharged with a diagnosis of BDP. The diagnosis of BDP is usually delayed, and there are only sporadic reports on its association with polyneuropathy, especially in patients with preserved limb muscle function. Therefore, when physicians encounter patients that are difficult to wean from mechanical ventilation, CIP associated with BDP should be considered in the differential diagnosis. PMID:26252301

  2. Fibrillary glomerulonephritis combined with chronic inflammatory demyelinating polyneuropathy

    PubMed Central

    Sung, Woo Kyung; Jeong, Jin Uk; Bang, Ki Tae; Shin, Jong Ho; Yoo, Ji Hyung; Kim, Nak Min; Park, Jun Hyung; Kim, Joo Heon

    2015-01-01

    A 58-yr-old man presented with leg edema and subacute weakness of his bilateral lower extremities. Urinary and serum immunoelectrophoresis revealed the presence of lambda-type Bence Jones proteins. He was ultimately diagnosed with monoclonal gammopathy of undetermined significance (MGUS). A renal biopsy specimen showed fibrillary glomerulonephritis (FGN), which was randomly arranged as 12–20 m nonbranching fibrils in the basement membranes. Immunofluorescence studies were negative for immunoglobulin (Ig)G, IgM, IgA, C3, and kappa light chains in the capillary walls and mesangial areas. A Congo red stain for amyloid was negative. Electromyography and nerve conduction velocity examinations results were compatible with the presence of demyelinating polyneuropathy. This case showed a rare combination of FGN, without Ig deposition, and MGUS combined with chronic inflammatory demyelinating polyneuropathy (CIDP). PMID:26484033

  3. Rapidly Progressive Polyneuropathy in a Patient With Monoclonal Gammopathy

    PubMed Central

    Wang, Chen; Guan, Yu-Zhou; Cai, Qian-Qian; Su, Wei; Zhou, Dao-Bin; Li, Jian

    2016-01-01

    Abstract Neuropathy, the dominant clinical feature of POEMS syndrome, is typically distal, symmetric, and slowly progressive with demyelinating changes. After a gradual proximal spread, it usually results in severe muscle weakness and functional disabilities. Cases characterized by acute onset polyneuropathy are rarely described. In the present report, we describe a 32-year-old male diagnosed as POEMS syndrome, but presenting with a rapidly evolving polyneuropathy. Detailed clinical, electrophysiological, and genetic studies revealed a coexisting underdiagnosed inherited axonal neuropathy, namely Charcot-Marie-Tooth disease 2A2. The patient received lenalidomide-based chemotherapy and consolidated by autologous stem cell transplantation for his POEMS syndrome, which improved the neurological disability. In most conditions, only 1 cause is responsible for a patient's polyneuropathy. However, an insidious inherited neuropathy can be overlooked, when an acquired condition is present. The case illustrated here, to the best of our knowledge, is the first one with coexistent axonal type Charcot-Marie-Tooth disease and POEMS syndrome, suggesting that an unrecognized inherited neuropathy may change the disease course of a further acquired neuropathy. PMID:27100445

  4. Heterogeneity of Polyneuropathy Associated with Anti-MAG Antibodies

    PubMed Central

    Magy, Laurent; Kaboré, Raphaël; Mathis, Stéphane; Lebeau, Prisca; Ghorab, Karima; Caudie, Christiane; Vallat, Jean-Michel

    2015-01-01

    Polyneuropathy associated with IgM monoclonal gammopathy and anti-myelin associated glycoprotein (MAG) antibodies is an immune-mediated demyelinating neuropathy. The pathophysiology of this condition is likely to involve anti-MAG antibody deposition on myelin sheaths of the peripheral nerves and it is supposed to be distinct from chronic inflammatory demyelinating neuropathy (CIDP), another immune-mediated demyelinating peripheral neuropathy. In this series, we have retrospectively reviewed clinical and laboratory findings from 60 patients with polyneuropathy, IgM gammopathy, and anti-MAG antibodies. We found that the clinical picture in these patients is highly variable suggesting a direct link between the monoclonal gammopathy and the neuropathy. Conversely, one-third of patients had a CIDP-like phenotype on electrodiagnostic testing and this was correlated with a low titer of anti-MAG antibodies and the absence of widening of myelin lamellae. Our data suggest that polyneuropathy associated with anti-MAG antibodies is less homogeneous than previously said and that the pathophysiology of the condition is likely to be heterogeneous as well with the self-antigen being MAG in most of the patients but possibly being another component of myelin in the others. PMID:26065001

  5. Electrophysiological features of POEMS syndrome and chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Guo, Xiuming; Qin, Xinyue; Zhang, Yuping; Huang, Cheng; Yu, Gang

    2014-04-01

    Polyneuropathy is often an initial manifestation of polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes (POEMS) syndrome and therefore this disorder is frequently misdiagnosed as chronic inflammatory demyelinating polyneuropathy (CIDP). We reviewed electrophysiological data in 20 patients with POEMS syndrome and 36 matched patients with CIDP to compare the electrophysiological features of POEMS syndrome and CIDP. Compared with CIDP controls, POEMS patients demonstrated (1) less prolonged distal motor latency and less reduced motor nerve and sensory nerve conduction velocities, (2) greater reduction of amplitudes of compound motor action potentials (CMAP) in distal stimulation, and similar reduction of amplitudes of CMAP in proximal stimulation, (3) similar reduction of amplitudes of sensory nerve action potentials (SNAP) in median and ulnar nerves, and a greater reduction of amplitudes of SNAP in tibial and peroneal nerves, (4) less temporal dispersion, (5) less frequent conduction block, (6) more frequent neurogenic injury in the muscles of the upper and lower limbs, and more frequent neurogenic injury in the muscles of the lower than upper limbs, (7) similar F wave and H reflex abnormalities, and (8) less frequent skin sympathetic response abnormalities. We concluded that before development of typical clinical manifestations, POEMS neuropathy can be distinguished from CIDP by neural electrophysiological examination. These electrophysiological features can be used for early diagnosis and initiating correct treatment of POEMS syndrome. PMID:24268501

  6. Shoe-makers' polyneuropathy in Italy: the aetiological problem.

    PubMed Central

    Abbritti, G; Siracusa, A; Cianchetti, C; Coli, A; Curradi, F; Perticoni, G F; De Rosa, F

    1976-01-01

    Since 1957, when the first cases of the so-called shoe-makers' toxic polyneuropathy were reported, nearly 400 cases have been described in the Italian literature. The substance that was considered to be responsible for the disease was triorthocresylphosphate (TOCP) contained in glues, artificial leathers, and some types of paints. However numerous chemical analyses of glues and leathers taken from factories where cases of the disease occurred have shown that in almost all instances little or no TOCP was present. In addition the disease manifests itself more frequently during winter and spring and this is not consistent with the absorption of the causative agent through the skin and/or gastrointestinal tract. In order to clarify the aetiology of the disease 122 workers in the shoe industry affected by toxic polymeuropathy during the period 1971-74 were studied. Workplaces where cases of polyneuropathy had occurred were visited and samples of glues and solvents were taken for chemical analysis. The polyneuropathy chiefly affects workers engaged in glueing and in the cleaning process, but it also affects those who do not have direct contact with glues or solvents. The disease is more common in women (68%) than in men (32%) and, in its more severe form begins with overwhelming prevalence during winter and early spring regardless of the job performed. No direct relationship has been found between the severity of the disease and the number of years of work in the shoe industry or of specific exposure (that is the number of years of work in the activity performed at the onset of the disease). The polyneuropathy is found almost exclusively among workers of the artisam type in small shoe factories, where standards of hygiene are low. Chemical analysis of glues and cleaning fluids collected from five different factories, where 20 cases of polyneuropathy occurred, showed the presence of paraffin hydrocarbons with a low boiling point (pentane, 2-methyl-pentane, 3-methyl

  7. Autoantibodies against vinculin in patients with chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Beppu, Minako; Sawai, Setsu; Satoh, Mamoru; Mori, Masahiro; Kazami, Takahiro; Misawa, Sonoko; Shibuya, Kazumoto; Ishibashi, Masumi; Sogawa, Kazuyuki; Kado, Sayaka; Kodera, Yoshio; Nomura, Fumio; Kuwabara, Satoshi

    2015-10-15

    To identify the target molecules of chronic inflammatory demyelinating polyneuropathy (CIDP), we used proteomic-based approach in the extracted proteins from porcine cauda equina. Two of 31 CIDP patients had markedly elevated serum autoantibodies against vinculin, a cell adhesion protein. Both of the patients with anti-vinculin antibodies had similar clinical manifestation, which are compatible with those of "typical" CIDP. Immunocytochemistry showed that vinculin was stained at the myelin sheath of the sciatic nerves by serum samples. Our results suggest that vinculin is a possible immunological target molecule in a subpopulation of typical CIDP patients. PMID:26439954

  8. Celiac disease manifested by polyneuropathy and swollen ankles

    PubMed Central

    Djuric, Zlatko; Kamenov, Borislav; Katic, Vuka

    2007-01-01

    A 27-year-old male started to have his ankles swollen during his military service. He was examined at a military hospital where electromyoneurography showed the signs of distal sensory-motor polyneuropathy with axon demyelinization and weak myopathic changes, whereas histopathological examination of gastrocnemius muscle biopsy revealed some mild and nonspecific myopathy. Besides, he was found to have subcutaneous ankle tissue edemas and hypertransaminasemia. Due to these reasons, he was dismissed from the military service and examined at another hospital where bone osteodensitometry revealed low bone mineral density of the spine. However, his medical problems were not resolved and after the second discharge from hospital he was desperately seeing doctors from time to time. Finally, at our institution he was shown to have celiac disease (CD) by positive serology (antitissue transglutaminase and antiendomysial antibodies) and small bowel mucosal histopathological examination, which showed total small bowel villous atrophy. Three months after the initiation of gluten-free diet, his ankle edema disappeared, electromyoneurographic signs of polyneuropathy improved and liver aminotransferases normalized. Good knowledge of CD extraintestinal signs and serologic screening are essential for early CD recognition and therapy. PMID:17552018

  9. Laryngeal paralysis-polyneuropathy complex in young Rottweilers.

    PubMed

    Mahony, O M; Knowles, K E; Braund, K G; Averill, D R; Frimberger, A E

    1998-01-01

    Five Rottweiler puppies from 3 unrelated litters developed inspiratory stridor at 11-13 weeks of age. Physical examination disclosed tetraparesis in all dogs, and bilateral lenticular cataracts in 4 dogs. Laryngeal examination under light anesthesia showed laryngeal paralysis in all dogs. Electrodiagnostic testing revealed denervation potentials in the distal appendicular muscles of 4 dogs tested and in the intrinsic laryngeal muscles of 2 dogs tested. Motor nerve conduction velocity was slightly low in 1 dog. Neurogenic muscular atrophy was found in distal appendicular muscles (n = 3) and intrinsic laryngeal muscles (n = 2), and degenerative changes were found in peripheral nerves (n = 3) and recurrent laryngeal nerves (n = 2). No abnormalities were detected in the spinal cord, spinal nerve roots, or ganglia of 3 dogs autopsied. The clinical, electrophysiologic, and histopathologic findings support a diagnosis of polyneuropathy and resemble the finding reported in young Dalmatians. Young dogs with laryngeal paralysis should be evaluated neurologically to rule out a more generalized polyneuropathy. The condition is suspected to be hereditary in nature and the prognosis is poor. PMID:9773408

  10. The spectrum of polyneuropathies in patients infected with HIV.

    PubMed Central

    Leger, J M; Bouche, P; Bolgert, F; Chaunu, M P; Rosenheim, M; Cathala, H P; Gentilini, M; Hauw, J J; Brunet, P

    1989-01-01

    Twenty five patients with peripheral neuropathy at different stages of human immunodeficiency virus (HIV) infection are reported. Cerebrospinal fluid (CSF) findings were available in 17 cases, electrophysiology in all and a neuromuscular biopsy in 11. Of six otherwise asymptomatic HIV+ patients, five had chronic inflammatory demyelinating polyneuropathy (CIDP) and one acute inflammatory demyelinating polyneuropathy (AIDP). CSF showed pleocytosis in all cases. Infiltration of the endoneurium and/or the epineurium by mononuclear cells was seen in biopsies from three cases. These six patients recovered either spontaneously, or with corticosteroids or plasmaphereses. Of five patients with AIDS related complex (ARC), three had distal predominantly sensory peripheral neuropathy (DSPN), one CIDP and one mixed neuropathy. Of 14 patients with AIDS, one had mononeuropathy multiplex and 13 painful DSPN. Electrophysiological studies were consistent with an axonopathy. Nerve biopsies in six cases showed axonal changes but surprisingly associated with marked segmental demyelination in two cases. Cell infiltration was present in nerve samples in two cases. Five patients died within six months after the onset of the neuropathy. PMID:2559161

  11. Near-infrared spectrophotoscopy of finger venules in assessment of autonomic dysfunction.

    PubMed

    Obayashi, K; Ando, Y; Nakamura, M; Yamashita, T; Ueda, M; Haraoka, K; Terazaki, H; Uchino, M

    2004-07-13

    The authors evaluated morphologic changes in the venules of the finger using near-infrared spectrophotoscopy in patients with autonomic dysfunction, such as familial amyloidotic polyneuropathy and multiple-system atrophy. Abnormalities of the venules, such as tortuosity, irregular venous caliber, and microaneurysm-like change, and a linear negative correlation between the degree of orthostatic hypotension and the degree of vasoconstriction of the venules were observed. PMID:15249631

  12. [Methylprednisolone pulse in treatment of childhood chronic inflammatory demyelinating polyneuropathy].

    PubMed

    Rafai, M A; Boulaajaj, F Z; Sekkat, Z; El Moutawakkil, B; Slassi, I

    2010-09-01

    Chronic inflammatory demyelinating polyneuropathy (CIDP) in children is rare and treatment is based primarily on intravenous immunoglobulins or oral corticosteroids. Boluses of methylprednisolone (MP) are a possible alternative. We report 3 cases of CIDP in children with good outcome after MP pulse therapy. One male (7 years of age) and 2 females (4 and 5 years of age) presented with recurring episodes of functional impotence of both lower limbs and walking impairment, partially reversible without treatment. Clinical and electrophysiological data and the analysis of the cerebrospinal fluid were compatible with CIDP. MP pulses were administered: the total number of pulses varied from 5 to 8, very satisfactory progression on the clinical and electrophysiological pattern was noted, without recurrence in the 3 cases. Childhood CIDP presents clinical, electrophysiological outcome, and prognostic particularities, recurring readily, and the outcome is good. Boluses of MP are an alternative for treatment of these neuropathies in childhood. PMID:20709511

  13. Acute peripheral polyneuropathy with multiorgan failure: a diagnostic dilemma

    PubMed Central

    Hussain, Kosar; Abubaker, Jawed; Ahmad Dar, Javeed; Ahmed, Raees

    2014-01-01

    We describe the case of a young man who presented with abdominal pain, vomiting and acute symmetric peripheral polyneuropathy. He was noted to have high anion gap metabolic acidosis with high lactate levels and persistently high arterial and venous pO2 values. The cerebrospinal fluid was acellular with a high protein and the nerve conduction study was consistent with axonal sensorimotor neuropathy. His clinical condition deteriorated rapidly despite full supportive care and he subsequently died of multiorgan failure. An extensive workup for various infectious, autoimmune and other possible aetiologies was carried out to identify the underlying cause for his fulminant illness. All diagnostic workup was non-conclusive except for a significantly elevated serum aluminium level. We have discussed the possibility of aluminium phosphide poisoning in view of the clinical presentation. PMID:24899008

  14. Chronic inflammatory demyelinating polyneuropathy associated with diabetes mellitus

    PubMed Central

    Fatehi, Farzad; Nafissi, Shahriar; Basiri, Keivan; Amiri, Mostafa; Soltanzadeh, Akbar

    2013-01-01

    Various forms of neuropathy are seen diabetic patients; chronic inflammatory demyelinating polyneuropathy (CIDP) seems not to be infrequent neuropathy in patients suffering from diabetes and it seems to be more common than in the general population; on the contrary, some authorities do not support pathogenetic association between diabetes mellitus (DM) and CIDP. Also, there are some controversies on the subject of CIDP treatment in diabetic patients. Some studies showed that patients with CIDP-DM considerably had recovered following treatment with immunotherapeutic modalities like (Intravenous immunoglobulin) IVIG and conversely, some else have argued against the prescription of IVIG in this group and recommend treatment with corticosteroids and provided that resistant, rituximab may be beneficial. The main limitation in most studies is the inadequate number of cases and as a result, problematic decision making in treatment. This article represents an inclusive review of diabetic CIDP presentation and treatment. PMID:24174953

  15. Treatment of diabetic polyneuropathy with the neurotrophic peptide ORG 2766.

    PubMed

    Valk, G D; Kappelle, A C; Tjon-A-Tsien, A M; Bravenboer, B; Bakker, K; Michels, R P; Groenhout, C M; Bertelsmann, F W

    1996-03-01

    The efficacy of the neurotrophic peptide ORG 2766 in diabetic patients with polyneuropathy was evaluated in a double-blind, placebo-controlled, multicentre trial. One hundred and twenty four patients were randomised in five groups to receive 0.1, 0.4, 2 or 5 mg ORG 2766 or placebo, once daily, administered subcutaneously 52 weeks. Thermal discrimination thresholds (TDT) and vibration perception thresholds (VPT), motor and sensory nerve conduction velocity, Hoffmann reflex, heart rate variation during deep breathing and heart rate response after standing up, neurological examination score and neuropathic symptom score were determined at baseline and after 17, 34 and 52 weeks of treatment. Of the nerve function indices studied, at week 52 the TDTwarmth of the hand in the ORG 2766 0.1, 0.4 and 5 mg groups and the TDTcold of the foot in the ORG 2766 0.1 and 0.4 mg groups significantly improved compared with placebo. Further significant improvement as compared with placebo was observed in the paraesthesia score at week 34 and week 52 in the ORG 2766 2 mg group. Only at week 34 had both the heartbeat variation during deep breathing and the VPT of the foot in the ORG 2766 0.1 mg group improved significantly, compared with placebo. No further statistically significant differences were observed at time for the other measures. No adverse reactions were observed. The only recorded drug-induced side effect was pain at the injection site. Taking all measures of efficacy into account, the statistically significant results observed did not show consistency within each measure. Therefore, it is concluded that ORG 2766, in contrast to earlier reports, is not effective in treating diabetic polyneuropathy. PMID:8936356

  16. Correlation Between the Severity of Diabetic Peripheral Polyneuropathy and Glycosylated Hemoglobin Levels: A Quantitative Study

    PubMed Central

    Lee, Won-Jae; Jang, Sol; Lee, Seung-Hwa

    2016-01-01

    Objective To investigate risk factors for diabetic peripheral polyneuropathy and their correlation with the quantified severity of nerve dysfunction in patients with diabetes mellitus (DM). Methods A total of 187 diabetic patients with clinically suspected polyneuropathy (PN) were subclassified into 2 groups according to electrodiagnostic testing: a DM-PN group of 153 diabetic patients without electrophysiological abnormality and a DM+PN group of 34 diabetic patients with polyneuropathy. For all patients, age, sex, height, weight, duration of DM, and plasma glycosylated hemoglobin (HbA1c) level were comparatively investigated. A composite score was introduced to quantitatively analyze the results of the nerve conduction studies. Logistic regression analysis and multiple regression analysis were used to evaluate correlations between significant risk factors and severity of diabetic polyneuropathy. Results The DM+PN group showed a significantly higher HbA1c level and composite score, as compared with the DM-PN group. Increased HbA1c level and old age were significant predictive factors for polyneuropathy in diabetic patients (odds ratio=5.233 and 4.745, respectively). In the multiple linear regression model, HbA1c and age showed a significant positive association with composite score, in order (β=1.560 and 0.253, respectively). Conclusion Increased HbA1c level indicative of a state of chronic hyperglycemia was a risk factor for polyneuropathy in diabetic patients and a quantitative measure of its severity. PMID:27152276

  17. Angioblast Derived from ES Cells Construct Blood Vessels and Ameliorate Diabetic Polyneuropathy in Mice

    PubMed Central

    Kamiya, Hideki; Naruse, Keiko; Cheng, Zhao; Ito, Sachiko; Shibata, Taiga; Kondo, Masaki; Kato, Jiro; Okawa, Tetsuji; Fujiya, Atsushi; Suzuki, Hirohiko; Kito, Tetsutaro; Hamada, Yoji; Oiso, Yutaka; Isobe, Kenichi; Nakamura, Jiro

    2015-01-01

    Background. Although numerous reports addressing pathological involvements of diabetic polyneuropathy have been conducted, a universally effective treatment of diabetic polyneuropathy has not yet been established. Recently, regenerative medicine studies in diabetic polyneuropathy using somatic stem/progenitor cell have been reported. However, the effectiveness of these cell transplantations was restricted because of their functional and numerical impairment in diabetic objects. Here, we investigated the efficacy of treatment for diabetic polyneuropathy using angioblast-like cells derived from mouse embryonic stem cells. Methods and Results. Angioblast-like cells were obtained from mouse embryonic stem cells and transplantation of these cells improved several physiological impairments in diabetic polyneuropathy: hypoalgesia, delayed nerve conduction velocities, and reduced blood flow in sciatic nerve and plantar skin. Furthermore, pathologically, the capillary number to muscle fiber ratios were increased in skeletal muscles of transplanted hindlimbs, and intraepidermal nerve fiber densities were ameliorated in transplanted plantar skin. Transplanted cells maintained their viabilities and differentiated to endothelial cells and smooth muscle cells around the injection sites. Moreover, several transplanted cells constructed chimeric blood vessels with recipient cells. Conclusions. These results suggest that transplantation of angioblast like cells induced from embryonic stem cells appears to be a novel therapeutic strategy for diabetic polyneuropathy. PMID:25977928

  18. Parenteral nutrition improves nutritional status, autonomic symptoms and quality of life in transthyretin amyloid polyneuropathy.

    PubMed

    Russo, Massimo; Vita, Gian Luca; Stancanelli, Claudia; Mazzeo, Anna; Vita, Giuseppe; Messina, Sonia

    2016-06-01

    Transthyretin familial amyloid polyneuropathy (TTR-FAP) is an inherited amyloidosis, leading to death in about ten years in most cases due to cardiac failure or wasting syndrome. Previous studies showed that modified body mass index was related to time before death, duration of gastrointestinal disturbances, malabsorption and functional capacity. We report two patients in whom nutritional status worsened despite diet modification, hypercaloric supplement and two relevant therapeutic approaches such as liver transplant and tafamidis meglumine, respectively. The first patient, a 52-year-old lady carrying Thr49Ala mutation, had a disease duration of twelve years and had lost weight up to 35 kg because of daily diarrhea. The second patient, a 63-year-old man with Glu89Gln mutation and a disease duration of fifteen years, was in the New York Heart Association (NYHA) Functional Classification class III and his weight was 39 kg. In both cases, a peripherally inserted central catheter was placed for parenteral nutrition. It allowed to improve their nutritional status and clinical conditions, with body weight gains of 11 and 8 kg in a one year follow-up, respectively. Moreover, reduction of autonomic symptoms including postural hypotension, nausea and diarrhoea was recorded with ameliorated quality of life. Our experience suggests that parenteral nutrition may be useful in reducing complications and disabilities in TTR-FAP patients, even when all dietary adjustments have been ineffective. Reasonably, the improvement in nutritional status may prolong survival in TTR-FAP patients. PMID:27132122

  19. Plasma exchange and chlorambucil in polyneuropathy associated with monoclonal IgM gammopathy. IgM-associated Polyneuropathy Study Group.

    PubMed Central

    Oksenhendler, E; Chevret, S; Léger, J M; Louboutin, J P; Bussel, A; Brouet, J C

    1995-01-01

    The study compared chlorambucil alone with chlorambucil in combination with plasma exchange in patients with polyneuropathy associated with monoclonal IgM. Forty four patients were prospectively randomly assigned, in a comparative open trial, to receive either 0.1 mg/kg/day chlorambucil orally, for 12 months or chlorambucil associated with 15 courses of plasma exchange, during the first four months of treatment. They were evaluated by a neuropathy disability score and nerve conduction studies. No difference was found between the two treatment groups. The average neuropathy disability score improved by 2.1 points from baseline (21.0 to 18.9) in the chlorambucil group and by 1.8 points (20.4 to 18.6) in the chlorambucil + plasma exchange group (P = 0.70). The mean motor nerve conduction velocity decreased from 20.0 to 18.2 m/s in the chlorambucil group and increased from 20.5 to 22.5 m/s in the chlorambucil + plasma exchange group (P = 0.51). A slight improvement of the sensory component of the neuropathy disability score (from 10.5 to 8.3) was noted in both groups (P = 0.01). At the end of the study and according to self evaluation, 15 patients--eight from the chlorambucil group and seven from the chlorambucil + plasma exchange group--reported clinical improvement, whereas 15--eight from the chlorambucil group and seven from the chlorambucil + plasma exchange group--reported clinical worsening. Neuropathy remained stable in the others. Thus plasma exchange seemed to confer no additional benefit in the treatment of polyneuropathy associated with monoclonal IgM. PMID:7673949

  20. Clinical development of an antisense therapy for the treatment of transthyretin-associated polyneuropathy.

    PubMed

    Ackermann, Elizabeth J; Guo, Shuling; Booten, Sheri; Alvarado, Luis; Benson, Merrill; Hughes, Steve; Monia, Brett P

    2012-06-01

    Transthyretin (TTR)-associated amyloidosis is a late-onset autosomal-dominant genetic disease. Over 100 amyloidogenic mutations have been identified in TTR which destabilize the TTR tetramer thereby inducing the formation of amyloid fibrils in tissues such as the heart and peripheral nerves. This disease mainly affects peripheral nerves, causing familial amyloid polyneuropathy (FAP) or heart, causing familial amyloid cardiomyopathy (FAC). Circulating TTR is predominantly produced by liver, and the only widely available clinical treatment for FAP is orthotopic liver transplantation (OLT), whereas no treatment currently exists for FAC. Using second-generation antisense technology, we identified an antisense oligonucleotide (ASO) targeting TTR, ISIS-TTR(Rx), for the treatment of TTR-associated amyloidosis. When tested in a human TTR transgenic mouse model (hTTR Ile84Ser), ISIS-TTR(Rx) showed a dose-dependent reduction of human TTR (up to >80%) at both the mRNA and protein levels. In cynomolgus monkeys, ISIS-TTR(Rx) treatment produced a time-dependent reduction in plasma TTR levels. After 12 weeks of treatment in monkey, liver TTR mRNA and plasma TTR protein levels were reduced by ~80%. As expected, treatment with ISIS-TTR(Rx) also produced a significant decrease in plasma RBP4 levels that correlated with reductions in TTR levels. ISIS-TTR(Rx) treatment was well tolerated in both rodents and monkeys and produced a PK/PD profile consistent with prior experiences using this chemistry platform. ISIS-TTR(Rx) is currently under evaluation in a Phase 1 clinical trial in normal healthy volunteers, and interim results of this trial will be presented. PMID:22494066

  1. An ARHGEF10 Deletion Is Highly Associated with a Juvenile-Onset Inherited Polyneuropathy in Leonberger and Saint Bernard Dogs

    PubMed Central

    Minor, Katie M.; Shelton, G. Diane; Patterson, Edward E.; Bley, Tim; Oevermann, Anna; Bilzer, Thomas; Leeb, Tosso

    2014-01-01

    An inherited polyneuropathy (PN) observed in Leonberger dogs has clinical similarities to a genetically heterogeneous group of peripheral neuropathies termed Charcot-Marie-Tooth (CMT) disease in humans. The Leonberger disorder is a severe, juvenile-onset, chronic, progressive, and mixed PN, characterized by exercise intolerance, gait abnormalities and muscle atrophy of the pelvic limbs, as well as inspiratory stridor and dyspnea. We mapped a PN locus in Leonbergers to a 250 kb region on canine chromosome 16 (Praw = 1.16×10−10, Pgenome, corrected = 0.006) utilizing a high-density SNP array. Within this interval is the ARHGEF10 gene, a member of the rho family of GTPases known to be involved in neuronal growth and axonal migration, and implicated in human hypomyelination. ARHGEF10 sequencing identified a 10 bp deletion in affected dogs that removes four nucleotides from the 3′-end of exon 17 and six nucleotides from the 5′-end of intron 17 (c.1955_1958+6delCACGGTGAGC). This eliminates the 3′-splice junction of exon 17, creates an alternate splice site immediately downstream in which the processed mRNA contains a frame shift, and generates a premature stop codon predicted to truncate approximately 50% of the protein. Homozygosity for the deletion was highly associated with the severe juvenile-onset PN phenotype in both Leonberger and Saint Bernard dogs. The overall clinical picture of PN in these breeds, and the effects of sex and heterozygosity of the ARHGEF10 deletion, are less clear due to the likely presence of other forms of PN with variable ages of onset and severity of clinical signs. This is the first documented severe polyneuropathy associated with a mutation in ARHGEF10 in any species. PMID:25275565

  2. Regulatory T and B lymphocytes in a spontaneous autoimmune polyneuropathy.

    PubMed

    Quan, S; Sheng, J R; Abraham, P M; Soliven, B

    2016-04-01

    B7-2(-/-) non-obese diabetic (NOD) mice develop a spontaneous autoimmune polyneuropathy (SAP) that mimics the progressive form of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). In this study, we focused on the role of regulatory T cells (Tregs ) and regulatory B cells (Bregs ) in SAP. We found that deletion of B7-2 in female NOD mice led to a lower frequency and number of Tregs and Bregs in spleens and lymph nodes. Tregs but not Bregs suppressed antigen-stimulated splenocyte proliferation, whereas Bregs inhibited the T helper type 1 (Th1) cytokine response. Both Tregs and Bregs induced an increase in CD4(+) interleukin (IL)-10(+) cells, although less effectively in the absence of B7-2. Adoptive transfer studies revealed that Tregs , but not Bregs , suppressed SAP, while Bregs attenuated disease severity when given prior to symptom onset. B cell deficiency in B cell-deficient (muMT)/B7-2(-/-) NOD mice prevented the development of SAP, which would indicate that the pathogenic role of B cells predominates over its regulatory role in this model. We conclude that Bregs and Tregs control the immunopathogenesis and progression of SAP in a non-redundant fashion, and that therapies aimed at expansion of Bregs and Tregs may be an effective approach in autoimmune neuropathies. PMID:26671281

  3. Influence Of Low Intensity Laser Therapy On Diabetic Polyneuropathy

    NASA Astrophysics Data System (ADS)

    Abdel-Raoof, N. A.; Elnhas, N. G.; Elsayed, I. M.

    2011-09-01

    Diabetic peripheral neuropathy is a consequence of diabetes-mediated impairment of blood flow, and resultant hypoxia of nerves that may develop within 10 years of the onset of diabetes in 40-50% of people with type 1 or type 2 diabetes. Low Intensity Laser Therapy (LILT) has been advocated for the treatment of chronic pain disorders as blood flow is an important determinant for pain relief. Comparing the effect of Helium-Neon Laser therapy versus Infrared laser therapy on blood vessels diameter and flow as well as level of sensation for neuropathy. Twenty diabetic patients suffering from neuropathy were enrolled in the study with age 45-55 years. They were assigned randomly into two equal groups in number; Group A underwent an application of He-Neon laser while Group B underwent an application of Infrared laser. Both groups received laser for 2 months. Blood flow velocity, and blood vessel diameter were investigated by using duplex Doppler ultrasound and peripheral neuropathy parameters were investigated by Semmes-Weinstein monofilament assessment. The results revealed that He-Neon laser as well as Infrared laser groups showed significant improvement in blood flow velocity, blood vessel diameter & neuropathy tested parameters after treatment but there was no significance difference between the two types of LILT. LILT is a safe, non-invasive and drug free method for improving blood flow & sensation in patients suffering from diabetic polyneuropathy in addition to preventing one of the most threatening microvascular complications of diabetes.

  4. New vistas in the diagnosis of diabetic polyneuropathy.

    PubMed

    Papanas, Nikolaos; Ziegler, Dan

    2014-12-01

    New modalities are now available to improve the diagnosis of diabetic polyneuropathy (DPN). The present review discusses the progress achieved in this area. First, the minimal diagnostic criteria have been better clarified. Moreover, there are now new bedside tests available, such as the indicator test Neuropad, NeuroQuick, Ipswich Touch Test (IpTT), Vibratip, NC-stat(®)/DPNCheck™ for automated nerve conduction study (NCS), tactile circumferential discriminator, steel ball-bearing, and SUDOSCAN(®), while more sophisticated modalities include skin biopsy and corneal confocal microscopy (CCM). Some tests can be used as screening tools, including primary care setting (Neuropad, IpTT, Vibratip, automated NCS), while others are more suitable for research, including evaluation of DPN in prospective studies (CCM, skin biopsy). Importantly, there is some evidence of earlier DPN diagnosis with the aid of some tests (Neuropad, skin biopsy, CCM). Further advantages provided by different tests are educational value and self-examination. Thus far, the potential of these tests has not been fully utilised. In particular, they have not been validated against standardised clinical examination scores in terms of predicting foot ulcers and amputations. Hence, it now remains to investigate the potential benefits from the widespread use of these tests for earlier and easier diagnosis of DPN in the everyday clinic. PMID:24839196

  5. Diagnosis and treatment of chronic acquired demyelinating polyneuropathies.

    PubMed

    Latov, Norman

    2014-08-01

    Chronic neuropathies are operationally classified as primarily demyelinating or axonal, on the basis of electrodiagnostic or pathological criteria. Demyelinating neuropathies are further classified as hereditary or acquired-this distinction is important, because the acquired neuropathies are immune-mediated and, thus, amenable to treatment. The acquired chronic demyelinating neuropathies include chronic inflammatory demyelinating polyneuropathy (CIDP), neuropathy associated with monoclonal IgM antibodies to myelin-associated glycoprotein (MAG; anti-MAG neuropathy), multifocal motor neuropathy (MMN), and POEMS syndrome. They have characteristic--though overlapping--clinical presentations, are mediated by distinct immune mechanisms, and respond to different therapies. CIDP is the default diagnosis if the neuropathy is demyelinating and no other cause is found. Anti-MAG neuropathy is diagnosed on the basis of the presence of anti-MAG antibodies, MMN is characterized by multifocal weakness and motor conduction blocks, and POEMS syndrome is associated with IgG or IgA λ-type monoclonal gammopathy and osteosclerotic myeloma. The correct diagnosis, however, can be difficult to make in patients with atypical or overlapping presentations, or nondefinitive laboratory studies. First-line treatments include intravenous immunoglobulin (IVIg), corticosteroids or plasmapheresis for CIDP; IVIg for MMN; rituximab for anti-MAG neuropathy; and irradiation or chemotherapy for POEMS syndrome. A correct diagnosis is required for choosing the appropriate treatment, with the aim of preventing progressive neuropathy. PMID:24980070

  6. Mechanisms and management of diabetic painful distal symmetrical polyneuropathy.

    PubMed

    Tesfaye, Solomon; Boulton, Andrew J M; Dickenson, Anthony H

    2013-09-01

    Although a number of the diabetic neuropathies may result in painful symptomatology, this review focuses on the most common: chronic sensorimotor distal symmetrical polyneuropathy (DSPN). It is estimated that 15-20% of diabetic patients may have painful DSPN, but not all of these will require therapy. In practice, the diagnosis of DSPN is a clinical one, whereas for longitudinal studies and clinical trials, quantitative sensory testing and electrophysiological assessment are usually necessary. A number of simple numeric rating scales are available to assess the frequency and severity of neuropathic pain. Although the exact pathophysiological processes that result in diabetic neuropathic pain remain enigmatic, both peripheral and central mechanisms have been implicated, and extend from altered channel function in peripheral nerve through enhanced spinal processing and changes in many higher centers. A number of pharmacological agents have proven efficacy in painful DSPN, but all are prone to side effects, and none impact the underlying pathophysiological abnormalities because they are only symptomatic therapy. The two first-line therapies approved by regulatory authorities for painful neuropathy are duloxetine and pregabalin. α-Lipoic acid, an antioxidant and pathogenic therapy, has evidence of efficacy but is not licensed in the U.S. and several European countries. All patients with DSPN are at increased risk of foot ulceration and require foot care, education, and if possible, regular podiatry assessment. PMID:23970715

  7. Three Turkish families with different transthyretin mutations.

    PubMed

    Bekircan-Kurt, Can Ebru; Güneş, Nalan; Yılmaz, Arda; Erdem-Özdamar, Sevim; Tan, Ersin

    2015-09-01

    Transthyretin (TTR)-related hereditary amyloidosis, also called familial amyloid polyneuropathy (FAP), is a rare autosomal dominant systemic disorder that presents with progressive axonal sensory, autonomic and/or motor neuropathies. The present report describes three families with three different TTR mutations who were followed from 1995 to 2014. Only one of these families expressed the Val30Met mutation, which is the most common mutation in endemic regions; all members of this family had late disease onset but varied severities and clinical presentations of the disease. The second family expressed the Thr49Ser mutation, which has not been well documented previously. Our limited experience obtained from these patients indicates that this mutation presents with autonomic neuropathy but a greater degree of cardiac involvement, especially fatal heart failure. The third mutation, Glu54Lys, has been identified as a cause of severe familial amyloid polyneuropathy; the family members with this mutation exhibited severe motor and autonomic neuropathy, early vitreous opacity, and fatal heart failure. Three of the patients with the Val30Met mutation were treated with tafamidis for longer than one year and cessation of the polyneuropathy resulted. However, a short trial of tafamidis in two patients with the Glu54Lys mutation, who showed severe systemic and neurological involvement, did not gain any clinical benefits. PMID:26115788

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

    PubMed Central

    Miura, Yumako; Devaux, Jérôme J.; Fukami, Yuki; Manso, Constance; Belghazi, Maya; Wong, Anna Hiu Yi

    2015-01-01

    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. PMID:25808373

  9. Immunoglobulin gene analysis in polyneuropathy associated with IgM monoclonal gammopathy.

    PubMed

    Eurelings, Marijke; Notermans, Nicolette C; Lokhorst, Henk M; van Kessel, Berris; Jacobs, Bart C; Wokke, John H J; Sahota, Surinder S; Bloem, Andries C

    2006-06-01

    Antineural antibody activity is the implicated pathogenic mechanism in polyneuropathy associated with monoclonal gammopathy. Recognition of antigen depends on immunoglobulin variable regions, encoded by V genes. We studied V(H)DJ(H) and V(L)J(L) gene use in monoclonal B cells by clonal analysis in 20 patients with polyneuropathy and IgM monoclonal gammopathy. V genes associated with bacterial responses appear over-represented and V(H)3-23 was preferentially used, without association with specific D, J(H) or V(L)J(L). V genes revealed somatic mutation and intraclonal variation was found in 9 of 20 patients. Polyneuropathy associated with monoclonal gammopathy may be caused by an immune response to bacterial antigens, which recruit somatically mutated autoreactive B cells. PMID:16600385

  10. Effects of aldose reductase inhibitor treatment in diabetic polyneuropathy - a clinical and neurophysiological study.

    PubMed Central

    Fagius, J; Jameson, S

    1981-01-01

    The efficacy of treatment with an aldose reductase inhibitor (1,3-dioxo-1 H-benz-de-isoquinoline-2(3H)-acetic acid, AY-22,284, Alrestatin) on peripheral nerve function in diabetic polyneuropathy was assessed. Thirty patients with long-standing diabetes and slight to moderate neuropathy participated in the double-blind placebo trial. Clinical examination, sensory threshold determinations for vibratory, tactile and thermal stimuli, conduction velocity measurements and studies of automatic function were performed to evaluate the treatment. Significant differences favouring Alrestatin over placebo were found for many of the measured variables, whereas no changes occurred on placebo. The apparent improvement of neuropathy occurred despite persisting hyperglycaemia. The results indicate that aldose reductase inhibitor treatment may be of value in diabetic polyneuropathy, and provide support for the sorbitol pathway hypothesis of diabetic polyneuropathy. PMID:6801211

  11. [Diabetic somatic polyneuropathy. Pathogenesis, clinical manifestations and therapeutic concepts].

    PubMed

    Hilz, M J; Marthol, H; Neundörfer, B

    2000-06-01

    Diabetic polyneuropathy is the most frequent neuropathy in western countries. In Germany, there are 3.5 to 4 million diabetic patients. Diagnosis should rule out other polyneuropathies and assess two out of the five diagnostic criteria: neuropathic symptoms, neuropathic deficits, pathological nerve conduction studies, pathological quantitative sensory testing and pathological quantitative autonomic testing. So far, the pathophysiology of diabetic neuropathy remains to be fully understood. Among the various pathophysiological concepts are the Sorbitol-Myo-Inositol hypothesis attributing Myo-Inositol depletion to the accumulation of Sorbitol and Fructose, the concept of deficiency of essential fatty acids with reduced availability of gamma-linolenic-acid and prostanoids, the pseudohypoxia- and hypoxia-hypothesis attributing endothelial and axonal dysfunction and structural lesions to increased oxidative stress and free radical production. Obviously, the hyperglycemia induced generation of advanced glycation end products (AGEs) also contributes to structural dysfunctions and lesions. Elevated levels of circulating immune complexes and activated T-lymphocytes as well the identification of autoantibodies against vagus nerve or sympathetic ganglia support the concept of an immune mediated neuropathy. The reduction of neurotrophic factors such as nerve growth factor, neurotrophin-3 or insulin-like growth factors also seems to further diabetic neuropathy. The symmetrical, distally pronounced and predominantly sensory neuropathy is far more frequent than the symmetrical neuropathy with predominant motor weakness or the asymmetrical neuropathy. The painless neuropathy manifests with impaired light touch sensation, position sense, vibratory perception and diminished or absent ankle deep tendon reflexes. The painful sensory diabetic neuropathy primarily affects small nerve fibers and accounts for decreased temperature perception and paresthesias. The proximal, diabetic

  12. Impaired dendritic cell function in a spontaneous autoimmune polyneuropathy.

    PubMed

    Quan, Songhua; Kim, Hye-Jung; Dukala, Danuta; Sheng, Jian Rong; Soliven, Betty

    2015-05-01

    Spontaneous autoimmune polyneuropathy (SAP) in B7-2 knockout NOD mice mimics the progressive form of chronic inflammatory demyelinating polyradiculoneuropathy, and is mediated by myelin protein zero (P0)-reactive Th1 cells. In this study, we focused on the effect of B7-2 deletion on the function of dendritic cells (DCs) within the context of SAP. We found that development of SAP was associated with a preponderance or increase of CD11b(+) DCs in peripheral lymph nodes and sciatic nerves. B7-2 deletion led to altered immunophenotypic properties that differ between CD11b(+) DCs and CD8α(+) DCs. Both DC subsets from B7-2 knockout NOD mice exhibited impaired capacity to capture fluorophore-labeled myelin P0, but diminished Ag-presenting function was observed only in CD11b(+) DCs. Clinical assessment, electrophysiologic studies, and splenocyte proliferation studies revealed that absence of B7-2 on DCs was sufficient to cause impaired ability to induce tolerance to P0, which could be overcome by preconditioning with IL-10. Tolerance induction by Ag-pulsed wild-type NOD DCs was dependent on IL-10 and was associated with increased CD4(+) regulatory T cells, whereas tolerance induction by IL-10-conditioned B7-2-deficient DCs was associated with increased percentages of both regulatory T cells and B10 cells in the spleen. We conclude that B7-2 deletion has an impact on the distribution of DC subsets in lymphoid organs and alters the expression of costimulatory molecules, but functional consequences are not uniform across DC subsets. Defective tolerance induction in the absence of B7-2 can be restored by preconditioning of DCs with IL-10. PMID:25825437

  13. Two sisters with mental retardation, cataract, ataxia, progressive hearing loss, and polyneuropathy.

    PubMed Central

    Begeer, J H; Scholte, F A; van Essen, A J

    1991-01-01

    Two sisters are described with a disorder characterised by mental retardation, congenital cataract, progressive spinocerebellar ataxia, sensorineural deafness, and signs of peripheral neuropathy. Progressive hearing loss, ataxia, and polyneuropathy became evident in the third decade. The differential diagnosis of this syndrome is discussed including the syndromes described by Berman et al and Koletzko et al. PMID:1661780

  14. Rehabilitation of Critical Illness Polyneuropathy and Myopathy Patients: An Observational Study

    ERIC Educational Resources Information Center

    Novak, Primoz; Vidmar, Gaj; Kuret, Zala; Bizovicar, Natasa

    2011-01-01

    Critical illness polyneuropathy and myopathy (CIPNM) frequently develops in patients hospitalized in intensive care units. The number of patients with CIPNM admitted to inpatient rehabilitation is increasing. The aim of this study was to comprehensively evaluate the outcome of their rehabilitation. Twenty-seven patients with CIPNM were included in…

  15. [Amyloidosis and familial Mediterranean fever].

    PubMed

    Pras, M

    1986-01-01

    Familial Mediterranean Fever (F. M. F.) is an autosomal recessive disorder occurring most commonly in Sepharadi Jews and Armenians. Two phenotypic features characterize the disease: brief episodic febrile attacks of peritonitis, pleuritis or synovitis recurring from childhood or adolescence and the development of systemic amyloidosis. Attacks are accompanied by striking elevations of acute phase proteins, including serum amyloid A protein. The amyloidosis of Familial Mediterranean Fever is of the AA type, and manifest clinically as a nephropathy that passes through proteinuria, nephrotic and uremic stages to renal death. Although there is ethnic variation in the incidence of amyloidosis of F. M. F. in our patient population--predominantly Sepharadi Jews of North African extraction--an amyloidotic death at an early age is their genetic destiny. Since the introduction in 1972 of colchicine to prevent the febrile attacks, the drug has been proven and become the main stay of therapy. Today, colchicine has been shown to be effective in preventing amyloidosis as well as the febrile attacks in Familial Mediterranean Fever. End stage renal disease is not the end of the road for patients with F.M.F. because of improving outlook for dialysis and renal transplantation in these patients. PMID:2943362

  16. Inability to experimentally produce a polyneuropathy in dogs given chronic oral low level lead.

    PubMed Central

    Steiss, J E; Braund, K G; Clark, E G

    1985-01-01

    Electromyographic examinations were performed at various times over a 40 week period in four mature dogs receiving chronic oral low doses of lead acetate and a control dog receiving sodium acetate. Blood lead levels in the four dogs were elevated (mean values 1.15, 2.18, 1.13 and 1.72 mumol/liter). No clinical signs of lead intoxication were present. Two dogs had evidence of a nonregenerative anemia. Neither needle electromyographic nor nerve conduction velocity studies showed evidence of a polyneuropathy. Teased nerve fiber preparations of proximal and distal segments of the ulnar and tibial nerves and muscle biopsies of distal appendicular muscles were normal in all dogs. Light microscopic examination of the brain, kidneys and liver revealed no abnormalities in the two dogs necropsied. In conclusion, a polyneuropathy was not produced experimentally in dogs ingesting low doses of inorganic lead for up to 40 weeks. PMID:3000550

  17. A Rare Case of Polyneuropathy and Monoclonalgammopathy with Recurrent Acute Kidney Injury

    PubMed Central

    Kim, Eun Jung; Shin, Dong Ho; Jeon, Hee Jung; Rhee, So Yon; Nam, Eun Sook; Park, Ji Young

    2016-01-01

    POEMS syndrome is a rare paraneoplastic syndrome and there are few reports of polyneuropathy and monoclonal gammopathy associated with kidney dysfunction. Here, we report a case of POEMS syndrome with recurrent acute kidney injury (AKI). A 52-year-old man presented with bilateral aggravating paresthesia and latermotor weakness of the lower extremities accompanied by repeated elevation of serum creatinine. The patient was finally diagnosed with POEMS syndrome on the basis of fulfilling the two mandatory major criteria (polyneuropathy and monoclonal gammopathy), one other major criterion (sclerotic bone lesion), and several minor criteria. A renal biopsy was performed to clarify the cause of AKI and showed membranoproliferative glomerulonephritis-like lesions with mesangiolysis and endothelial cell injury. This case illustrates that renal manifestations, not included in the diagnostic criteria for POEMS, can be apparent before various other systemic symptoms. PMID:27453713

  18. [Sporadic recurrent hypertrophic polyneuropathy. Clinical-histological contributions on differential diagnosis].

    PubMed

    Haferkamp, G; Regli, F

    1976-01-01

    The authors report about an own case of recurrent sporadic hypertrophic polyneuropathy and describe the clinical course and histologic picture with reference to the literature. The disease is characterized by recurrences of subacutely occurring polyradiculoneuropathy and sequent nearly complete remission. Clinical examination discloses preferentially symmetrically and distally occurring motor paresis while sensibility in most cases is less affected. The peripheral nerves may be enlarged after a few relapses and frequently painful to pressure during the bout. Excessive increase in CSF proteins is found only during the bout. Motor nerve conduction velocity is considerably reduced. Histological pictures typically present an onion bulb formation of the Schwann cells with marked proliferation of connective tissue. There frequently younger individuals are involved; the relation female to male is 3:1. Differentiation has to be made concerning hereditary and symptomatic forms of hypertrophic polyneuropathy. Etiological factors of the disease are discussed. PMID:185690

  19. Adult Patient with Novel H1N1 Infection Presented with Encephalitis, Rhabdomyolysis, Pneumonia and Polyneuropathy.

    PubMed

    Patel, Ketan K; Patel, Atul K; Shah, Shalin; Ranjan, Rajiv; Shah, Sudhir V

    2012-07-01

    Neurological complications of influenza are well known. Influenza A is commonly associated with neurological complications. Neurological complications especially encephalitis is described in the pediatric age group of patients with current pandemic novel H1N1 infection. We are describing a case of novel H1N1 infection presenting with multi-system involvement (encephalitis, bilateral pneumonia, severe rhabdomyolysis leading to renal failure and polyneuropathy) in adult patient. PMID:23055650

  20. Adult Patient with Novel H1N1 Infection Presented with Encephalitis, Rhabdomyolysis, Pneumonia and Polyneuropathy

    PubMed Central

    Patel, Ketan K; Patel, Atul K; Shah, Shalin; Ranjan, Rajiv; Shah, Sudhir V

    2012-01-01

    Neurological complications of influenza are well known. Influenza A is commonly associated with neurological complications. Neurological complications especially encephalitis is described in the pediatric age group of patients with current pandemic novel H1N1 infection. We are describing a case of novel H1N1 infection presenting with multi-system involvement (encephalitis, bilateral pneumonia, severe rhabdomyolysis leading to renal failure and polyneuropathy) in adult patient. PMID:23055650

  1. Is heat hypoalgesia a useful parameter in quantitative thermal testing of alcoholic polyneuropathy?

    PubMed

    Hilz, M J; Claus, D; Neundörfer, B; Zimmermann, P; Berić, A

    1994-12-01

    Detection of thermal hypoaesthesia, hyperalgesia, and paradoxical sensation significantly contribute to the diagnosis of polyneuropathy (PNP). There is controversy about the clinical usefulness of detected heat hypoalgesia. In 50 chronic alcoholic patients we compared the prevalence and diagnostic value of heat hypoalgesia (HPT) to that of cold (CT) and warm (WT) hypoaesthesia using a "Marstock" thermotest. Clinical examination revealed PNP in 56%, cold hypoaesthesia was present in 62%, warm hypoaesthesia in 24%, paradoxical thermal sensation in 10%, cold and heat hyperalgesia in 12%, and heat hypoalgesia in 22%. Only 1 patient (2%) presented with heat hypoalgesia but normal warm and cold thresholds; he reported paradoxical thermal sensation and had PNP. One patient suffered first degree burn injury from heat pain examination. Heat hypoalgesia contributed least to the diagnosis of polyneuropathy (HPT versus CT: P < 0.001). In patients with sensory loss, testing heat hypoalgesia bears some risk of burn injury. In contrast to thermal hypoaesthesia and hyperalgesia, it does not significantly enrich the diagnostic workup of alcoholic polyneuropathies. PMID:7969246

  2. [Polyneuropathy and central nervous system diseases before and after heart transplantation. Is cyclosporin neurotoxic?].

    PubMed

    Porschke, H; Strenge, H; Stauch, C

    1991-10-18

    In a cross-sectional study, 52 patients (44 men, 8 women, mean age 50.6 [19-68] years) were investigated clinically and electrophysiologically for evidence of peripheral and central nervous system damage before and after heart transplantation. 20 patients were investigated before heart transplantation (group 1), 16 at 7 days to 5 months after transplantation (early post-operative group; group 2) and 16 at 6 to 32 months after transplantation (late post-operative group; group 3). Nerve conduction studies (median, peroneal and sural nerves) revealed polyneuropathy in 14 out of 16 patients in group 2, significantly more than in group 1 (11 out of 19) and group 3 (9 out of 16). The mean blood cyclosporin concentration was 656 ng/ml in group 2 and 409 ng/ml in group 3 (P less than 0.001). Patients in group 3 with polyneuropathy had significantly higher cyclosporin concentrations than patients without polyneuropathy (505 vs 284 ng/ml; P less than 0.01). Among patients who had undergone operations, there were no noteworthy differences between the mean cyclosporin concentrations and clinical data in those with or without central nervous system lesions. There is preliminary evidence of a neurotoxic effect of cyclosporin on the peripheral but not the central nervous system. PMID:1935623

  3. Evaluation of distal symmetric polyneuropathy: the role of autonomic testing, nerve biopsy, and skin biopsy (an evidence-based review).

    PubMed

    England, J D; Gronseth, G S; Franklin, G; Carter, G T; Kinsella, L J; Cohen, J A; Asbury, A K; Szigeti, K; Lupski, J R; Latov, N; Lewis, R A; Low, P A; Fisher, M A; Herrmann, D; Howard, J F; Lauria, G; Miller, R G; Polydefkis, M; Sumner, A J

    2009-01-01

    Distal symmetric polyneuropathy (DSP) is the most common variety of neuropathy. Since the evaluation of this disorder is not standardized, the available literature was reviewed to provide evidence-based guidelines regarding the role of autonomic testing, nerve biopsy, and skin biopsy for the assessment of polyneuropathy. A literature review using MEDLINE, EMBASE, Science Citation Index, and Current Contents was performed to identify the best evidence regarding the evaluation of polyneuropathy published between 1980 and March 2007. Articles were classified according to a four-tiered level of evidence scheme and recommendations were based on the level of evidence. (1) Autonomic testing may be considered in the evaluation of patients with polyneuropathy to document autonomic nervous system dysfunction (Level B). Such testing should be considered especially for the evaluation of suspected autonomic neuropathy (Level B) and distal small fiber sensory polyneuropathy (SFSN) (Level C). A battery of validated tests is recommended to achieve the highest diagnostic accuracy (Level B). (2) Nerve biopsy is generally accepted as useful in the evaluation of certain neuropathies as in patients with suspected amyloid neuropathy, mononeuropathy multiplex due to vasculitis, or with atypical forms of chronic inflammatory demyelinating polyneuropathy (CIDP). However, the literature is insufficient to provide a recommendation regarding when a nerve biopsy may be useful in the evaluation of DSP (Level U). (3) Skin biopsy is a validated technique for determining intraepidermal nerve fiber (IENF) density and may be considered for the diagnosis of DSP, particularly SFSN (Level C). There is a need for additional prospective studies to define more exact guidelines for the evaluation of polyneuropathy. PMID:19086069

  4. Evaluation of distal symmetric polyneuropathy: the role of laboratory and genetic testing (an evidence-based review).

    PubMed

    England, J D; Gronseth, G S; Franklin, G; Carter, G T; Kinsella, L J; Cohen, J A; Asbury, A K; Szigeti, K; Lupski, J R; Latov, N; Lewis, R A; Low, P A; Fisher, M A; Herrmann, D; Howard, J F; Lauria, G; Miller, R G; Polydefkis, M; Sumner, A J

    2009-01-01

    Distal symmetric polyneuropathy (DSP) is the most common variety of neuropathy. Since the evaluation of this disorder is not standardized, the available literature was reviewed to provide evidence-based guidelines regarding the role of laboratory and genetic tests for the assessment of DSP. A literature review using MEDLINE, EMBASE, Science Citation Index, and Current Contents was performed to identify the best evidence regarding the evaluation of polyneuropathy published between 1980 and March 2007. Articles were classified according to a four-tiered level of evidence scheme and recommendations were based on the level of evidence. (1) Screening laboratory tests may be considered for all patients with polyneuropathy (Level C). Those tests that provide the highest yield of abnormality are blood glucose, serum B(12) with metabolites (methylmalonic acid with or without homocysteine), and serum protein immunofixation electrophoresis (Level C). If there is no definite evidence of diabetes mellitus by routine testing of blood glucose, testing for impaired glucose tolerance may be considered in distal symmetric sensory polyneuropathy (Level C). (2) Genetic testing is established as useful for the accurate diagnosis and classification of hereditary neuropathies (Level A). Genetic testing may be considered in patients with cryptogenic polyneuropathy who exhibit a hereditary neuropathy phenotype (Level C). Initial genetic testing should be guided by the clinical phenotype, inheritance pattern, and electrodiagnostic (EDX) features and should focus on the most common abnormalities, which are CMT1A duplication/HNPP deletion, Cx32 (GJB1), and MFN2 mutation screening. There is insufficient evidence to determine the usefulness of routine genetic testing in patients with cryptogenic polyneuropathy who do not exhibit a hereditary neuropathy phenotype (Level U). PMID:19086068

  5. [Nondeficiency chronic polyneuropathies in celiac disease in adults (2 cases with inflammatory neuromuscular vascularitis)].

    PubMed

    Bernier, J J; Buge, A; Rambaud, J C; Rancurel, G; Hauw, J J; Modigliani, R; Denvil, D

    1976-10-01

    The neurological and muscular complications seen in coeliac disease in adults are usually attributed to deficiency secondary to malabsorption. Amongst them, however, there exists a very rare cateogory, described by Cooke et al. (1966) taking the form of a chronic myeloneuropathy which cannot be explained in terms of the malabsorption syndrome. Our two cases of gluten intolerance enteropathy, confirmed by biopsy before and after diet, fell into this group of polyneuropathies. The patients, both women, suffered from an essentially sensory ataxic polyneuropathy with accessory motor component with pyramidal and posterior column signs. CSF findings showed a meningeal inflammatory reaction in one of the two cases. These neurological signs, appearing paradoxically during a digestive disease cured by diet, evolve chronically but become stabilised with corticosteroid therapy. Any vitamin deficiency may be excluded in the aetiology of these problems. Neuropathological study of neuromuscular biopsies in very fine serial sections confirmed the mild peripheral nervous involvement but revealed identical inflammatory lesions in the nerve and muscle which were remarkable by virtue of their very highly segmentally selective micro-vasculitis appearance. In these two cases, general, clinical and biological arguments, as well as the type of histological lesion, make it possible to exclude monoclonal gammapathies, malignant haemopathies, amyloidosis and the major collagen diseases. This micro-vasculitis, having transient forms with P.A.N. is no less distinctive, and may be integrated into the provisional group of "allergic angeitis", related to physiopathology of circulating immune complexes and very fashionable in theories as to the mechanism of gluten-sensitive enteropathies. The exact nature of the link between the latter and these types of polyneuropathy remains unknown. PMID:1008365

  6. Redistribution of joint moments is associated with changed plantar pressure in diabetic polyneuropathy

    PubMed Central

    Savelberg, Hans HCM; Schaper, Nicolaas C; Willems, Paul JB; de Lange, Ton LH; Meijer, Kenneth

    2009-01-01

    Background Patients with diabetic polyneuropathy (DPN) are often confronted with ulceration of foot soles. Increased plantar pressure under the forefoot has been identified as a major risk factor for ulceration. This study sets out to test the hypothesis that changes in gait characteristics induced by DPN related muscle weakness are the origin of the elevated plantar pressures. Methods Three groups of subjects participated: people diagnosed with diabetes without polyneuropathy (DC), people diagnosed with diabetic polyneuropathy (DPN) and healthy, age-matched controls (HC). In all subjects isometric strength of plantar and dorsal flexors was assessed. Moreover, joint moments at ankle, knee and hip joints were determined while walking barefoot at a velocity of 1.4 m/s. Simultaneously plantar pressure patterns were measured. Results Compared to HC-subjects, DPN-participants walked with a significantly increased internal plantar flexor moment at the first half of the stance phase. Also in DPN-subjects the maximal braking and propelling force applied to the floor was decreased. Moreover, in DPN-subjects the ratio of forefoot-to-rear foot plantar pressures was increased. Body-mass normalized strength of dorsal flexors showed a trend to be reduced in people with diabetes, both DC and DPN, compared to HC-subjects. Plantar flexors tended to be less weak in DC compared to HC and in DPN relative to DC. Conclusion The results of this study suggest that adverse plantar pressure patterns are associated with redistribution of joint moments, and a consequent reduced capacity to control forward velocity at heel strike. PMID:19192272

  7. Chronic Inflammatory Demyelinating Polyneuropathy Following Anti-TNF-α Therapy With Infliximab for Crohn's Disease.

    PubMed

    Kamel, Amir Y; Concepcion, Orestes; Schlachterman, Alexander; Glover, Sarah; Forsmark, Christopher Y

    2016-04-01

    We present a 29-year-old male with Crohn's disease who developed chronic inflammatory demyelinating polyneuropathy (CIDP) related to infliximab therapy. He developed lower extremity weakness and dysesthesia 3 weeks after a fourth infliximab dose. Laboratory examination revealed an elevated cerebrospinal fluid protein without pleocytosis. The patient initially responded to plasmapheresis therapy with marked symptomatic improvement, but relapsed and was refractory to subsequent treatments with plasmaphereisis, intravenous immunoglobulin, and glucocorticoids. While a causal relationship between infliximab and CIDP cannot be proven, clinicians should monitor Crohn's disease patients who are receiving TNF-α antagonists for neurologic symptoms suggestive of demyelinating disease. PMID:27144200

  8. Chronic Inflammatory Demyelinating Polyneuropathy Following Anti-TNF-α Therapy With Infliximab for Crohn's Disease

    PubMed Central

    Concepcion, Orestes; Schlachterman, Alexander; Glover, Sarah; Forsmark, Christopher Y.

    2016-01-01

    We present a 29-year-old male with Crohn's disease who developed chronic inflammatory demyelinating polyneuropathy (CIDP) related to infliximab therapy. He developed lower extremity weakness and dysesthesia 3 weeks after a fourth infliximab dose. Laboratory examination revealed an elevated cerebrospinal fluid protein without pleocytosis. The patient initially responded to plasmapheresis therapy with marked symptomatic improvement, but relapsed and was refractory to subsequent treatments with plasmaphereisis, intravenous immunoglobulin, and glucocorticoids. While a causal relationship between infliximab and CIDP cannot be proven, clinicians should monitor Crohn's disease patients who are receiving TNF-α antagonists for neurologic symptoms suggestive of demyelinating disease. PMID:27144200

  9. Human immunodeficiency virus infection and diffuse polyneuropathy. Implications for rehabilitation medicine.

    PubMed Central

    Mukand, J. A.

    1991-01-01

    Patients at various stages of human immunodeficiency virus (HIV) infection require rehabilitation services. These patients present problems for each of the disciplines in a rehabilitation team, and all team members must confront the psychosocial and ethical issues involved with the disease. Patients with HIV infection may have polyneuropathy with multisystem involvement, including dysphagia, autonomic dysfunction, respiratory failure, bowel and bladder dysfunction, generalized weakness, a painful sensory neuropathy, and depression. Guidelines are presented for determining if inpatient rehabilitation or other settings are appropriate. Case management is a valuable strategy for the rehabilitation of patients with this complicated disorder. PMID:1866948

  10. Hereditary and acquired polyneuropathy conditions of the peripheral nerves: clinical considerations and MR neurography imaging.

    PubMed

    Trivedi, Jaya R; Phillips, Lauren; Chhabra, Avneesh

    2015-04-01

    Polyneuropathies can be classified as either primarily demyelinating or axonal, and further as hereditary or acquired. It is important to recognize acquired neuropathies because some are amenable to treatment. Clinical findings and electrophysiology are used in the routine diagnosis of these conditions. Magnetic resonance neurography (MRN) is a helpful supplementary diagnostic tool. This article discusses the typical clinical findings, electrophysiology findings, and MRN appearances of common hereditary or acquired neuropathies such as chronic inflammatory demyelinating neuropathy, multifocal motor neuropathy, diabetic neuropathy, chemotherapy-induced neuropathy, and postsurgical neuropathy. PMID:25764237

  11. Serum cytokine and chemokine profiles in patients with chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Beppu, Minako; Sawai, Setsu; Misawa, Sonoko; Sogawa, Kazuyuki; Mori, Masahiro; Ishige, Takayuki; Satoh, Mamoru; Nomura, Fumio; Kuwabara, Satoshi

    2015-02-15

    To identify serum cytokine networks specific to chronic inflammatory demyelinating polyneuropathy (CIDP), serum samples of two subgroups (18 patients with typical CIDP and 12 patients with multifocal acquired demyelinating sensory and motor neuropathy [MADSAM]) were analyzed with multiplex magnetic bead-based cytokine assay. TNF-α, HGF, MIP-1β and IL-1β levels were significantly higher in total CIDP patients than in normal controls. Of these, HGF levels were elevated in typical CIDP patients, but not in MADSAM patients. Patients with high HGF levels showed good responses to steroid treatment. Different cytokine profiles among the CIDP subtypes presumably reflect differences in pathophysiology. PMID:25669993

  12. Geospatial association of endemicity of ataxic polyneuropathy and highly cyanogenic cassava cultivars

    PubMed Central

    2013-01-01

    Background Exposure to cyanide from cassava foods is present in communities where ataxic polyneuropathy is endemic. Ataxic polyneuropathy is endemic in coastal parts of southwest and southeast Nigeria, and coastal Newala, south India, but it has been reported in epidemic or endemic forms from Africa, Asia, or Caribbean. This study was done to determine if cyanogenicity of cassava cultivars is higher in lowland than highland areas, and if areas of endemicity of ataxic polyneuropathy colocalize with areas of highest cyanogenicity of cassava. Methods Roots of cassava cultivars were collected from 150 farmers in 32 of 37 administrative areas in Nigeria. Global positioning system was used to determine the location of the roots. Roots were assayed for concentrations of cyanogens. Thin Plate Spline regression was used to produce the contour map of cyanogenicity of the study area. Contour maps of altitude of the endemic areas were produced. Relationship of cyanogenicity of cassava cultivars and altitude, and of locations of areas of high cyanogenicity and areas of endemicity were determined. Results Geometrical mean (95% CI) cyanogen concentration was 182 (142–233) mg HCN eq/kg dry wt for cassava cultivars in areas ≤ 25 m above sea level, but 54 (43–66) mg HCN eq/kg dry wt for areas > 375 m. Non-spatial linear regression of altitude on logarithm transformed concentrations of cyanogens showed highly significant association, (p < 0.0001). Contour map of concentrations of cyanogens in cassava cultivars in Nigeria showed four areas with average concentrations of cassava cyanogens > 250 mg HCN eq/kg dry wt, and one area of moderately high cyanogen concentration > 150 mg HCN eq/kg dry wt. The endemic areas colocalized with areas of highest cassava cyanogenicity in lowland areas close to the Atlantic Ocean. Conclusion This study shows strong geospatial association of areas of endemicity of ataxic polyneuropathy and areas of highest cyanogenicity of

  13. Overview of the pathogenesis and treatment of chronic inflammatory demyelinating polyneuropathy with intravenous immunoglobulins

    PubMed Central

    Mahdi-Rogers, Mohamed; Rajabally, Yusuf A

    2010-01-01

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired heterogeneous disorder of immune origin affecting the peripheral nerves, causing motor weakness and sensory symptoms and signs. The precise pathophysiology of CIDP remains uncertain although B and T cell mechanisms are believed to be implicated. Intravenous immunoglobulins (IVIg) have been shown in a number of trials to be an effective treatment for CIDP. IVIg is thought to exert its immunomodulatory effects by affecting several components of the immune system including B-cells, T-cells, macrophages and complement. This article provides an overview of the pathogenesis of CIDP and of its treatment with IVIg. PMID:20376173

  14. [A case of acute motor sensory axonal polyneuropathy after Haemophilus influenzae infection].

    PubMed

    Oda, M; Udaka, F; Kubori, T; Oka, N; Kameyama, M

    2000-08-01

    A 47-year-old woman developed consciousness disturbance, and experienced hallucinations while traveling abroad, and then went into critical condition. She was placed in the critical care unit, and had flaccid tetraparesis requiring mechanical ventilation. Haemophilus influenzae was cultured from the sputum. The level of protein of the cerebrospinal fluid was elevated to 114 mg/dl, nerve conduction study showed findings of pure axonal damage, and the sural nerve biopsy revealed severe axonal degeneration. She improved gradually by plasma exchange. The diagnosis of acute motor sensory axonal polyneuropathy (AMSAN) based on autoimmune mechanism was made. We speculate that H. influenzae infection may have elicited AMSAN in this case. PMID:11218707

  15. Effects of sulbutiamine on diabetic polyneuropathy: an open randomised controlled study in type 2 diabetics.

    PubMed

    Kiew, K K; Wan Mohamad, W B; Ridzuan, A; Mafauzy, M

    2002-01-01

    Thirty patients with diabetic polyneuropathy were recruited from the diabetic clinic in Hospital Universiti Sains Malaysia from 1996 to 1998. They were randomly assigned either sulbutiamine (Arcalion(®)) (15 patients) or no treatment (control group; 15 patients). Glycaemic control was assessed by blood glucose and HbA1. Severity of neuropathy was assessed by symptom and sign score, and electrophysiological parameters (nerve conduction velocity and compound muscle action potential) at entry to the study and after 6 weeks. There were improvements in the electrophysiological parameters in the treatment group when compared to the controls with significant improvement in the median nerve conduction velocity (p<0.001), median compound muscle action potential (p<0.001), peroneal nerve conduction velocity (p<0.001), and peroneal compound muscle action potential (p<0.001). No significant improvement in symptom and sign scores were noted between the groups but a significant improvement compared to base line was noted for the sulbutiamine treated group. (p< 0.05). The glycaemic control in both groups was not significantly different at base line and was stable throughout the study. Sulbutiamine objectively improved peripheral nerve function in diabetic polyneuropathy although the symptom score did not improve, possibly due to the short duration of the study. PMID:22969314

  16. Effects of Sulbutiamine on Diabetic Polyneuropathy: An Open Randomised Controlled Study in Type 2 Diabetics

    PubMed Central

    Kiew, K.K.; Wan Mohamad, W.B.; Ridzuan, A.; Mafauzy, M.

    2002-01-01

    Thirty patients with diabetic polyneuropathy were recruited from the diabetic clinic in Hospital Universiti Sains Malaysia from 1996 to 1998. They were randomly assigned either sulbutiamine (Arcalion®) (15 patients) or no treatment (control group; 15 patients). Glycaemic control was assessed by blood glucose and HbA1. Severity of neuropathy was assessed by symptom and sign score, and electrophysiological parameters (nerve conduction velocity and compound muscle action potential) at entry to the study and after 6 weeks. There were improvements in the electrophysiological parameters in the treatment group when compared to the controls with significant improvement in the median nerve conduction velocity (p<0.001), median compound muscle action potential (p<0.001), peroneal nerve conduction velocity (p<0.001), and peroneal compound muscle action potential (p<0.001). No significant improvement in symptom and sign scores were noted between the groups but a significant improvement compared to base line was noted for the sulbutiamine treated group. (p< 0.05). The glycaemic control in both groups was not significantly different at base line and was stable throughout the study. Sulbutiamine objectively improved peripheral nerve function in diabetic polyneuropathy although the symptom score did not improve, possibly due to the short duration of the study. PMID:22969314

  17. Serial nerve conduction studies in vitamin B12 deficiency-associated polyneuropathy.

    PubMed

    Huang, Chi-Ren; Chang, Wen-Neng; Tsai, Nai-Wen; Lu, Cheng-Hsien

    2011-02-01

    This report is on a 22-year-old male vegetarian with acute polyneuropathy secondary to vitamin B(12) deficiency. He presented with weakness and numbness of the distal limbs and absent deep tendon reflex in all four extremities. Nerve conduction study (NCS) showed an axonal type sensori-motor polyneuropathy. Serum biochemical studies revealed vitamin B(12) level of 119 pg/mL (reference range 185-710 pg/mL), with elevated creatine kinase (CK) (719 U/L) and homocysteine (Hcy) (24.04 μmol/L) levels. Anti-parietal cell antibody test was positive. The patient received both oral and intramuscular injection of vitamin B(12). The amplitude of the median and ulnar motor NCS increased 2.5 months later, while muscle power of the ankle plantar flexion and dorsiflexion recovered after 3.5 and 5.5 months, respectively. Follow-up NCS after 14.5 months showed response in sural NCS, but not the peroneal NCS. Follow-up also showed decreased serum Hcy and CK to 9.6 μmol/L and 198 U/L, respectively, and increasing amplitude of response. Recovery sequence involved muscle power of the proximal muscles, hands, plantar flexion, and dorsiflexion of the feet, and followed by sensory conduction. PMID:20890625

  18. Intensive care unit acquired weakness in children: Critical illness polyneuropathy and myopathy

    PubMed Central

    Kukreti, Vinay; Shamim, Mosharraf; Khilnani, Praveen

    2014-01-01

    Background and Aims: Intensive care unit acquired weakness (ICUAW) is a common occurrence in patients who are critically ill. It is most often due to critical illness polyneuropathy (CIP) or to critical illness myopathy (CIM). ICUAW is increasingly being recognized partly as a consequence of improved survival in patients with severe sepsis and multi-organ failure, partly related to commonly used agents such as steroids and muscle relaxants. There have been occasional reports of CIP and CIM in children, but little is known about their prevalence or clinical impact in the pediatric population. This review summarizes the current understanding of pathophysiology, clinical presentation, diagnosis and treatment of CIP and CIM in general with special reference to published literature in the pediatric age group. Subjects and Methods: Studies were identified through MedLine and Embase using relevant MeSH and Key words. Both adult and pediatric studies were included. Results: ICUAW in children is a poorly described entity with unknown incidence, etiology and unclear long-term prognosis. Conclusions: Critical illness polyneuropathy and myopathy is relatively rare, but clinically significant sequelae of multifactorial origin affecting morbidity, length of intensive care unit (ICU) stay and possibly mortality in critically ill children admitted to pediatric ICU. PMID:24678152

  19. Systemic Lupus Erythematosus With Acute Inflammatory Demyelinating Polyneuropathy: A Case Report and Review of the Literature

    PubMed Central

    Li, Xiangling; Wang, Yanqiang

    2016-01-01

    We recently encountered a patient with acute inflammatory demyelinating polyneuropathy (AIDP) that was associated with systemic lupus erythematosus (SLE). A 34-year-old Chinese female with a 3-year history of SLE presented with acute bilateral leg weakness and paraparesis, and lost the ability to walk 1 day after noticing bilateral leg numbness and pain for 12 days. Physical examination revealed bilateral facial muscle paralysis, muscle strength in the legs with graded 1/5 proximally and 2/5 distally bilaterally and absence of deep tendon reflex in both knees and ankles. Paresthesia was observed in distal limbs with glove and stocking distribution. Cerebrospinal fluid analysis demonstrated albuminocytologic dissociation. Electrophysiologic survey also indicated sensory-motor demyelinating polyneuropathy. The diagnosis of SLE was established based on her initial symptoms including intermittent fevers, hair loss, oral ulcers, malar rash and arthritis affecting the elbow, wrist and hand joints; positive immunologic findings for antinuclear antibody (ANA), anti-DNA antibody, anti-Smith (anti-Sm) antibody, low serum complement levels, and the kidney biopsy specimen showed glomerular mesangial proliferation with focal endothelial cell proliferation (ISN/PPS 2004 classification lupus nephritis, class III). Treatment with intravenous immunoglobulin, methylprednisolone and cyclophosphamide resulted in clinical and electrophysiological improvement. PMID:27298667

  20. Systemic Lupus Erythematosus With Acute Inflammatory Demyelinating Polyneuropathy: A Case Report and Review of the Literature.

    PubMed

    Li, Xiangling; Wang, Yanqiang

    2016-07-01

    We recently encountered a patient with acute inflammatory demyelinating polyneuropathy (AIDP) that was associated with systemic lupus erythematosus (SLE). A 34-year-old Chinese female with a 3-year history of SLE presented with acute bilateral leg weakness and paraparesis, and lost the ability to walk 1 day after noticing bilateral leg numbness and pain for 12 days. Physical examination revealed bilateral facial muscle paralysis, muscle strength in the legs with graded 1/5 proximally and 2/5 distally bilaterally and absence of deep tendon reflex in both knees and ankles. Paresthesia was observed in distal limbs with glove and stocking distribution. Cerebrospinal fluid analysis demonstrated albuminocytologic dissociation. Electrophysiologic survey also indicated sensory-motor demyelinating polyneuropathy. The diagnosis of SLE was established based on her initial symptoms including intermittent fevers, hair loss, oral ulcers, malar rash and arthritis affecting the elbow, wrist and hand joints; positive immunologic findings for antinuclear antibody (ANA), anti-DNA antibody, anti-Smith (anti-Sm) antibody, low serum complement levels, and the kidney biopsy specimen showed glomerular mesangial proliferation with focal endothelial cell proliferation (ISN/PPS 2004 classification lupus nephritis, class III). Treatment with intravenous immunoglobulin, methylprednisolone and cyclophosphamide resulted in clinical and electrophysiological improvement. PMID:27298667

  1. [Opportunities for confocal and laser biomicroscopy of corneal nerves in diabetic polyneuropathy].

    PubMed

    Surnina, Z V

    2015-01-01

    The review concerns corneal nerves involvement in diabetes mellitus (DM), a pressing issue for ophthalmology and endocrinology. The history of research in this field along with anatomical, physiological, and biochemical features of corneal nerves is provided. Corneal nerves anatomy is described in accordance with Soviet scientific school and contemporary foreign sources. The most part of the paper is devoted to technical description of a confocal microscope and Heidelberg Retina Tomograph with corneal module as well as the feasibility of corneal nerves visualization. Diabetic neuropathy, a threatening complication of DM that can result in lower limb amputations, is discussed. A number of authors suggest confocal biomicroscopy for early diagnosis of polyneuropathy, yet few relevant publications can be found. If effective, confocal biomicroscopy can be considered as a possible screening tool able to detect early signs of diabetes complications and thus to ensure the treatment initiated in a timely manner. The latter is crucial to prevent DM progression to its terminal stage--diabetic polyneuropathy, which is dangerous of lower limb amputations. PMID:25872394

  2. Classical and lectin complement pathway activity in polyneuropathy associated with IgM monoclonal gammopathy.

    PubMed

    Stork, Abraham C J; Cats, Elisabeth A; Vlam, Lotte; Heezius, Erik; Rooijakkers, Suzan; Herpers, Bjorn; de Jong, Ben A W; Rijkers, Ger; van Strijp, Jos; Notermans, Nicolette C; van den Berg, Leonard H; van der Pol, W-Ludo

    2016-01-15

    Polyneuropathy associated with IgM monoclonal gammopathy (IgM-PNP) is a slowly progressive, sensorimotor neuropathy. It is assumed that complement activation contributes to IgM-PNP pathogenesis. We investigated whether innate differences in complement activity of the classical and mannose binding lectin (MBL) pathways are associated with IgM-PNP or its severity. We measured complement activity using ELISA and determined MBL serumc oncentrations and MBL gene polymorphisms in 83 patients and 83 healthy controls. We did not observe differences between IgM-PNP patients and healthy controls nor associations with different disease severities. Differences in innate complement activity are not likely to explain susceptibility to or severity of IgM-PNP. PMID:26711574

  3. Unilateral Cervical Polyneuropathies following Concurrent Bortezomib, Cetuximab, and Radiotherapy for Head and Neck Cancer

    PubMed Central

    Elghouche, Alhasan; Shokri, Tom; Qin, Yewen; Wargo, Susannah; Citrin, Deborah; Van Waes, Carter

    2016-01-01

    We report a constellation of cervical polyneuropathies in a patient treated with concurrent bortezomib, cetuximab, and cisplatin alongside intensity modulated radiotherapy for carcinoma of the tonsil with neck metastasis. The described deficits include brachial plexopathy, cervical sensory neuropathy, and oculosympathetic, recurrent laryngeal, and phrenic nerve palsies within the ipsilateral radiation field. Radiation neuropathy involving the brachial plexus is typically associated with treatment of breast or lung cancer; however, increased awareness of this entity in the context of investigational agents with potential neuropathic effects in head and neck cancer has recently emerged. With this report, we highlight radiation neuropathy in the setting of investigational therapy for head and neck cancer, particularly since these sequelae may present years after therapy and entail significant and often irreversible morbidity. PMID:27088023

  4. Office immunotherapy in chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy.

    PubMed

    Dyck, Peter J; Taylor, Bruce V; Davies, Jenny L; Mauermann, Michelle L; Litchy, William J; Klein, Christopher J; Dyck, P James B

    2015-10-01

    Intravenous immunoglobulin [IVIg], plasma exchange [PE], and corticosteroids are efficacious treatment in chronic inflammatory demyelinating polyneuropathy [CIDP]. IVIg is effective in multifocal motor neuropathy [MMN]. NIS, NIS-weakness, sum scores of raw amplitudes of motor fiber (CMAPs) amplitudes, and Dyck/Rankin score provided reliable measures to detect and scale abnormality and reflect change; they are therefore ideal for office management of response-based immunotherapy (R-IRx) of CIDP. Using efficacious R-IRx, a large early and late therapeutic response (≥ one-fourth were in remission or had recovered) was demonstrated in CIDP. In MMN only an early improvement with late non-significant worsening was observed. The difference in immunotherapy response supports a fundamental difference between CIDP (immune attack on Schwann cells and myelin) and MMN (attack on nodes of Ranvier and axons). PMID:25976871

  5. Mobile biofeedback of heart rate variability in patients with diabetic polyneuropathy: a preliminary study.

    PubMed

    Druschky, Katrin; Druschky, Achim

    2015-09-01

    Biofeedback of heart rate variability (HRV) was applied to patients with diabetic polyneuropathy using a new mobile device allowing regularly scheduled self-measurements without the need of visits to a special autonomic laboratory. Prolonged generation of data over an eight-week period facilitated more precise investigation of cardiac autonomic function and assessment of positive and negative trends of HRV parameters over time. Statistical regression analyses revealed significant trends in 11 of 17 patients, while no significant differences were observed when comparing autonomic screening by short-term HRV and respiratory sinus arrhythmia at baseline and after the 8 weeks training period. Four patients showed positive trends of HRV parameters despite the expected progression of cardiac autonomic dysfunction over time. Patient compliance was above 50% in all but two patients. The results of this preliminary study indicate a good practicality of the handheld device and suggest a potential positive effect on cardiac autonomic neuropathy in patients with type 2 diabetes. PMID:24438496

  6. Polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes (POEMS syndrome): a paraneoplastic syndrome

    PubMed Central

    Kumar, Sunil; Sharma, Shruti

    2015-01-01

    POEMS syndrome (Crow–Fukase syndrome) is a rare paraneoplastic disorder. It is characterized by peripheral neuropathy, elevated vascular endothelial growth factors (VEGFs), monoclonal gammopathy, sclerotic bone lesions and Castleman disease. Other important clinical features are organomegaly, edema, ascites, papilledema, endocrinopathy, skin changes and thrombocytosis. A high index of suspicion, a detailed clinical history and examination followed by appropriate laboratory investigations like VEGF level, radiological skeletal survey and bone marrow biopsy are required to diagnose POEMS syndrome. We report a case of POEMS syndrome who presented with insidious onset, progressive sensorimotor polyneuropathy, pedal edema, ascites, hepatomegaly, skin changes and hypothyroidism. X-ray of the pelvis showed osteosclerotic lesions. Immunoelectrophoresis using the immunofixation method revealed lambda chain monoclonal gammopathy. The patient was given radiotherapy, followed by a combination therapy of melphalan and dexamethasone. We emphasize the importance of recognizing a challenging diagnosis of a rare disease, which is shown to be treatment responsive. PMID:26634133

  7. Progressive chronic inflammatory demyelinating polyneuropathy in a child with central nervous system involvement and myopathy.

    PubMed

    Barisić, Nina; Horvath, Rita; Grković, Lana; Mihelcić, Dina; Luetić, Tomislav

    2006-12-01

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is a chronic disorder, manifesting with monophasic or relapsing course. Progressive course is rare in children. The article presents a boy with progressive generalized muscle weakness and areflexia since the age of two, developed after viral infection. Electromyoneurography showed severe neurogenic lesion, with myopathic pattern in proximal muscles. Increased serum ganglioside antibody titers (anti-GM1 and anti-GD1b) were registered. Sural nerve biopsy revealed demyelination and onion bulbs. Inflammatory perivascular CD3 positive infiltrates were present in muscle and nerve biopsies. Brain magnetic resonance imaging showed cortical atrophy, hyperintensities of the white matter and gray matter hypointensities. Improvement occurred on intravenous immune globulins and methylprednisolone treatment. Demyelination might develop in central and peripheral nervous system associated with inflammatory myopathy in patients with progressive course of CIDP. PMID:17243577

  8. Treatment of Chronic Inflammatory Demyelinating Polyneuropathy: From Molecular Bases to Practical Considerations

    PubMed Central

    Ripellino, Paolo; Fleetwood, Thomas; Cantello, Roberto; Comi, Cristoforo

    2014-01-01

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disease of the peripheral nervous system, in which both cellular and humoral immune responses are involved. The disease is clinically heterogeneous with some patients displaying pure motor form and others also showing a variable degree of sensory dysfunction; disease evolution may also differ from patient to patient, since monophasic, progressive, and relapsing forms are reported. Underlying such clinical variability there is probably a broad spectrum of molecular dysfunctions that are and will be the target of therapeutic strategies. In this review we first explore the biological bases of current treatments and subsequently we focus on the practical management that must also take into account pharmacoeconomic issues. PMID:24527207

  9. Experimentally Derived Structural Constraints for Amyloid Fibrils of Wild-Type Transthyretin

    PubMed Central

    Bateman, David A.; Tycko, Robert; Wickner, Reed B.

    2011-01-01

    Transthyretin (TTR) is a largely β-sheet serum protein responsible for transporting thyroxine and vitamin A. TTR is found in amyloid deposits of patients with senile systemic amyloidosis. TTR mutants lead to familial amyloidotic polyneuropathy and familial amyloid cardiomyopathy, with an earlier age of onset. Studies of amyloid fibrils of familial amyloidotic polyneuropathy mutant TTR suggest a structure similar to the native state with only a simple opening of a β-strand-loop-strand region exposing the two main β-sheets of the protein for fibril elongation. However, we find that the wild-type TTR sequence forms amyloid fibrils that are considerably different from the previously suggested amyloid structure. Using protease digestion with mass spectrometry, we observe the amyloid core to be primarily composed of the C-terminal region, starting around residue 50. Solid-state NMR measurements prove that TTR differs from other pathological amyloids in not having an in-register parallel β-sheet architecture. We also find that the TTR amyloid is incapable of binding thyroxine as monitored by either isothermal calorimetry or 1,8-anilinonaphthalene sulfonate competition. Taken together, our experiments are consistent with a significantly different configuration of the β-sheets compared to the previously suggested structure. PMID:22098747

  10. Experimentally derived structural constraints for amyloid fibrils of wild-type transthyretin.

    PubMed

    Bateman, David A; Tycko, Robert; Wickner, Reed B

    2011-11-16

    Transthyretin (TTR) is a largely β-sheet serum protein responsible for transporting thyroxine and vitamin A. TTR is found in amyloid deposits of patients with senile systemic amyloidosis. TTR mutants lead to familial amyloidotic polyneuropathy and familial amyloid cardiomyopathy, with an earlier age of onset. Studies of amyloid fibrils of familial amyloidotic polyneuropathy mutant TTR suggest a structure similar to the native state with only a simple opening of a β-strand-loop-strand region exposing the two main β-sheets of the protein for fibril elongation. However, we find that the wild-type TTR sequence forms amyloid fibrils that are considerably different from the previously suggested amyloid structure. Using protease digestion with mass spectrometry, we observe the amyloid core to be primarily composed of the C-terminal region, starting around residue 50. Solid-state NMR measurements prove that TTR differs from other pathological amyloids in not having an in-register parallel β-sheet architecture. We also find that the TTR amyloid is incapable of binding thyroxine as monitored by either isothermal calorimetry or 1,8-anilinonaphthalene sulfonate competition. Taken together, our experiments are consistent with a significantly different configuration of the β-sheets compared to the previously suggested structure. PMID:22098747

  11. Treatment of symptomatic polyneuropathy with actovegin in type 2 diabetic patients.

    PubMed

    Ziegler, Dan; Movsesyan, Lusine; Mankovsky, Boris; Gurieva, Irina; Abylaiuly, Zhangentkhan; Strokov, Igor

    2009-08-01

    OBJECTIVE To evaluate the efficacy and safety of actovegin in patients with diabetic polyneuropathy. RESEARCH DESIGN AND METHODS In this multicenter, randomized, double-blind trial, 567 patients with type 2 diabetes received 20 intravenous infusions of actovegin (2,000 mg/day) (n = 281) or placebo (n = 286) once daily followed by three tablets of actovegin (1,800 mg/day) or placebo three times daily for 140 days. Total symptom score (TSS) of the lower limbs and vibration perception threshold (VPT) were used as coprimary outcome measures, computed as the area under the curve (AUC) from repeated scores and divided by duration of exposure. Secondary end points included individual TSS symptoms, neuropathy impairment score of the lower limbs (NIS-LL), and quality of life (short form [SF]-36). RESULTS TSS was significantly improved during actovegin treatment compared with placebo, as assessed by AUC (-0.56 points [95% CI -0.85 to -0.27]; P = 0.0003), and from baseline to 160 days (-0.86 points [-1.22 to -0.50]; P < 0.0001). VPT (five sites per foot) decreased by 3% (95% CI 0-6; P = 0.084) with actovegin than placebo, as assessed by AUC, and by 5% (1-9; P = 0.017) after 160 days. NIS-LL sensory function, as assessed by AUC, was significantly improved with actovegin versus placebo (-0.25 [95% CI -0.46 to -0.04]; P = 0.021), as was the SF-36 mental health domain. There were no differences in the incidence of adverse events between the groups. CONCLUSIONS Sequential intravenous and oral actovegin treatment over 160 days improved neuropathic symptoms, VPT, sensory function, and quality of life in type 2 diabetic patients with symptomatic polyneuropathy. PMID:19470838

  12. Treatment of Symptomatic Polyneuropathy With Actovegin in Type 2 Diabetic Patients

    PubMed Central

    Ziegler, Dan; Movsesyan, Lusine; Mankovsky, Boris; Gurieva, Irina; Abylaiuly, Zhangentkhan; Strokov, Igor

    2009-01-01

    OBJECTIVE To evaluate the efficacy and safety of actovegin in patients with diabetic polyneuropathy. RESEARCH DESIGN AND METHODS In this multicenter, randomized, double-blind trial, 567 patients with type 2 diabetes received 20 intravenous infusions of actovegin (2,000 mg/day) (n = 281) or placebo (n = 286) once daily followed by three tablets of actovegin (1,800 mg/day) or placebo three times daily for 140 days. Total symptom score (TSS) of the lower limbs and vibration perception threshold (VPT) were used as coprimary outcome measures, computed as the area under the curve (AUC) from repeated scores and divided by duration of exposure. Secondary end points included individual TSS symptoms, neuropathy impairment score of the lower limbs (NIS-LL), and quality of life (short form [SF]-36). RESULTS TSS was significantly improved during actovegin treatment compared with placebo, as assessed by AUC (−0.56 points [95% CI −0.85 to −0.27]; P = 0.0003), and from baseline to 160 days (−0.86 points [−1.22 to −0.50]; P < 0.0001). VPT (five sites per foot) decreased by 3% (95% CI 0–6; P = 0.084) with actovegin than placebo, as assessed by AUC, and by 5% (1–9; P = 0.017) after 160 days. NIS-LL sensory function, as assessed by AUC, was significantly improved with actovegin versus placebo (−0.25 [95% CI −0.46 to −0.04]; P = 0.021), as was the SF-36 mental health domain. There were no differences in the incidence of adverse events between the groups. CONCLUSIONS Sequential intravenous and oral actovegin treatment over 160 days improved neuropathic symptoms, VPT, sensory function, and quality of life in type 2 diabetic patients with symptomatic polyneuropathy. PMID:19470838

  13. Tongue atrophy and fasciculations in transthyretin familial amyloid neuropathy

    PubMed Central

    Mozaffar, Tahseen

    2015-01-01

    Objective: Macroglossia is a well-known feature of amyloidosis; however, tongue atrophy and fasciculations are rarely seen and can lead to the misdiagnosis of amyotrophic lateral sclerosis (ALS). Methods: We identified 2 unrelated patients with atypical features of tongue atrophy and fasciculations in the setting of a severe neuropathy. Results: Both patients were confirmed to have transthyretin-related familial amyloid polyneuropathy (TTR-FAP) by genetic testing. Conclusions: TTR-FAP should be considered as a possible mimicker of ALS when tongue atrophy and fasciculations are seen in the setting of a severely progressive polyneuropathy. Other atypical mimickers of ALS include polyglucosan body disease, hexosaminidase A deficiency, multisystem proteinopathy, and Allgrove syndrome. PMID:27066555

  14. Sensorimotor polyneuropathy

    MedlinePlus

    ... chemotherapy Guillain-Barré syndrome Hereditary neuropathy Vitamin deficiency ( vitamins B12 , B1 , and E) ... CARE AND INDEPENDENCE Exercises and retraining to maximize function of the damaged nerves Job (vocational) therapy Occupational ...

  15. Pericarditis and chronic inflammatory demyelinating polyneuropathy during therapy with pegylated interferon alfa-2a for chronic hepatitis C.

    PubMed

    Nishio, Kazuaki; Konndo, Takeshi; Okada, Shunichi; Enchi, Machiko

    2010-09-27

    We report a case of pericarditis and chronic inflammatory demyelinating polyneuropathy with biological signs of a lupus-like syndrome due to pegylated interferon alfa-2a therapy during treatment for chronic hepatitis C. The patient developed moderate weakness in the lower limbs and dyspnea. He was hospitalized for congestive heart failure. An electrocardiogram showed gradual ST-segment elevation in leads V(1) through V(6) without coronary artery disease. A transthoracic cardiac ultrasonographic study revealed moderate pericardial effusion with normal left ventricular function. Anti-DNA antibody and antids DNA IgM were positive. Neurological examination revealed a symmetrical predominantly sensory polyneuropathy with impairment of light touch and pin prick in globe and stoking-like distribution. Treatment with prednisolone improved the pericarditis and motor nerve disturbance and the treatment with intravenous immunoglobulin improved the sensory nerve disturbance. PMID:21161021

  16. Pericarditis and chronic inflammatory demyelinating polyneuropathy during therapy with pegylated interferon alfa-2a for chronic hepatitis C

    PubMed Central

    Nishio, Kazuaki; Konndo, Takeshi; Okada, Shunichi; Enchi, Machiko

    2010-01-01

    We report a case of pericarditis and chronic inflammatory demyelinating polyneuropathy with biological signs of a lupus-like syndrome due to pegylated interferon alfa-2a therapy during treatment for chronic hepatitis C. The patient developed moderate weakness in the lower limbs and dyspnea. He was hospitalized for congestive heart failure. An electrocardiogram showed gradual ST-segment elevation in leads V1 through V6 without coronary artery disease. A transthoracic cardiac ultrasonographic study revealed moderate pericardial effusion with normal left ventricular function. Anti-DNA antibody and antids DNA IgM were positive. Neurological examination revealed a symmetrical predominantly sensory polyneuropathy with impairment of light touch and pin prick in globe and stoking-like distribution. Treatment with prednisolone improved the pericarditis and motor nerve disturbance and the treatment with intravenous immunoglobulin improved the sensory nerve disturbance. PMID:21161021

  17. Vincristine-induced polyneuropathy in a child with stage I Wilms’ tumour presenting with unilateral abducens nerve palsy

    PubMed Central

    Panjawatanan, Panadeekarn; Charoenkwan, Pimlak; Katanyuwong, Kamornwan; Choeyprasert, Worawut

    2014-01-01

    A 4-year-old boy presented with right esotropia while receiving vincristine and dactinomycin for stage I Wilms’ tumour according to the National Wilms Tumour Study-5 protocol. On examination, he had isolated limitation of his right lateral gaze. CT of the brain and cerebrospinal fluid examination were normal. A nerve conduction velocity study which was performed on the peripheral nerves revealed predominant motor polyneuropathy compatible with axonal loss involving the upper limbs. The patient had received a cumulative vincristine dose of 17 mg/m2 before developing esotropia. Vincristine-induced abducens nerve mononeuropathy and subclinical motor polyneuropathy was suspected. Unilateral esotropia markedly improved after the discontinuation of vincristine and a short course of oral pyridoxine treatment. PMID:24966267

  18. Curcumin: A multi-target disease-modifying agent for late-stage transthyretin amyloidosis.

    PubMed

    Ferreira, Nelson; Gonçalves, Nádia P; Saraiva, Maria J; Almeida, Maria R

    2016-01-01

    Transthyretin amyloidoses encompass a variety of acquired and hereditary diseases triggered by systemic extracellular accumulation of toxic transthyretin aggregates and fibrils, particularly in the peripheral nervous system. Since transthyretin amyloidoses are typically complex progressive disorders, therapeutic approaches aiming multiple molecular targets simultaneously, might improve therapy efficacy and treatment outcome. In this study, we evaluate the protective effect of physiologically achievable doses of curcumin on the cytotoxicity induced by transthyretin oligomers in vitro by showing reduction of caspase-3 activity and the levels of endoplasmic reticulum-resident chaperone binding immunoglobulin protein. When given to an aged Familial Amyloidotic Polyneuropathy mouse model, curcumin not only reduced transthyretin aggregates deposition and toxicity in both gastrointestinal tract and dorsal root ganglia but also remodeled congophilic amyloid material in tissues. In addition, curcumin enhanced internalization, intracellular transport and degradation of transthyretin oligomers by primary macrophages from aged Familial Amyloidotic Polyneuropathy transgenic mice, suggesting an impaired activation of naïve phagocytic cells exposed to transthyretin toxic intermediate species. Overall, our results clearly support curcumin or optimized derivatives as promising multi-target disease-modifying agent for late-stage transthyretin amyloidosis. PMID:27197872

  19. Curcumin: A multi-target disease-modifying agent for late-stage transthyretin amyloidosis

    PubMed Central

    Ferreira, Nelson; Gonçalves, Nádia P.; Saraiva, Maria J.; Almeida, Maria R.

    2016-01-01

    Transthyretin amyloidoses encompass a variety of acquired and hereditary diseases triggered by systemic extracellular accumulation of toxic transthyretin aggregates and fibrils, particularly in the peripheral nervous system. Since transthyretin amyloidoses are typically complex progressive disorders, therapeutic approaches aiming multiple molecular targets simultaneously, might improve therapy efficacy and treatment outcome. In this study, we evaluate the protective effect of physiologically achievable doses of curcumin on the cytotoxicity induced by transthyretin oligomers in vitro by showing reduction of caspase-3 activity and the levels of endoplasmic reticulum-resident chaperone binding immunoglobulin protein. When given to an aged Familial Amyloidotic Polyneuropathy mouse model, curcumin not only reduced transthyretin aggregates deposition and toxicity in both gastrointestinal tract and dorsal root ganglia but also remodeled congophilic amyloid material in tissues. In addition, curcumin enhanced internalization, intracellular transport and degradation of transthyretin oligomers by primary macrophages from aged Familial Amyloidotic Polyneuropathy transgenic mice, suggesting an impaired activation of naïve phagocytic cells exposed to transthyretin toxic intermediate species. Overall, our results clearly support curcumin or optimized derivatives as promising multi-target disease-modifying agent for late-stage transthyretin amyloidosis. PMID:27197872

  20. Human transthyretin in complex with iododiflunisal: structural features associated with a potent amyloid inhibitor

    PubMed Central

    2005-01-01

    Ex vivo and in vitro studies have revealed the remarkable amyloid inhibitory potency and specificity of iododiflunisal in relation to transthyretin [Almeida, Macedo, Cardoso, Alves, Valencia, Arsequell, Planas and Saraiva (2004) Biochem. J. 381, 351–356], a protein implicated in familial amyloidotic polyneuropathy. In the present paper, the crystal structure of transthyretin complexed with this diflunisal derivative is reported, which enables a detailed analysis of the protein–ligand interactions. Iododiflunisal binds very deep in the hormone-binding channel. The iodine substituent is tightly anchored into a pocket of the binding site and the fluorine atoms provide extra hydrophobic contacts with the protein. The carboxylate substituent is involved in an electrostatic interaction with the Nζ of a lysine residue. Moreover, ligand-induced conformational alterations in the side chain of some residues result in the formation of new intersubunit hydrogen bonds. All these new interactions, induced by iododiflunisal, increase the stability of the tetramer impairing the formation of amyloid fibrils. The crystal structure of this complex opens perspectives for the design of more specific and effective drugs for familial amyloidotic polyneuropathy patients. PMID:15689188

  1. Toxic polyneuropathy due to gingili oil contaminated with tri-cresyl phosphate affecting adolescent girls in Sri Lanka.

    PubMed

    Senanayake, N; Jeyaratnam, J

    1981-01-10

    An outbreak of acute polyneuropathy affected over 20 young females in Sri Lanka during 1977-78. The illness was restricted to girls attaining menarche and to women after childbirth. The cause of the neuropathy could be traced to tri-cresyl phosphate found as a contaminant in gingili oil. Contamination probably occurred during transport of the oil in containers previously used for storing mineral oils. PMID:6109132

  2. Electrodiagnostic criteria for polyneuropathy and demyelination: application in 135 patients with Guillain-Barré syndrome. Dutch Guillain-Barré Study Group.

    PubMed Central

    Meulstee, J; van der Meché, F G

    1995-01-01

    Since the development of effective but expensive therapeutic strategies for the treatment of Guillain-Barré syndrome, early confirmation of the diagnosis has become very important. Electrodiagnostic criteria were developed for the discrimination of polyneuropathy and in particular for demyelination. The sensitivity and specificity of these criteria were determined in 135 patients with Guillain-Barré syndrome in an early stage of the disease, along with 45 healthy volunteers. The algorithms used to develop our criteria consisted of sets of selected electrodiagnostic variables, each of them relevant to the detection of polyneuropathy. Each set was applied on all of three consecutive electrodiagnostic examinations within one month of disease onset. Application of the best set resulted in 85% of patients with Guillain-Barré syndrome fulfilling the criteria for polyneuropathy at the first examination (mean time interval six days of disease onset), whereas none of the healthy volunteers fulfilled the criteria (sensitivity 85%, specificity 100%). The set of criteria for the detection of demyelination was fulfilled by 60% during the first examination (by 66% and 72% during the second and third examination). Application of criteria for demyelinating polyneuropathy as defined by others resulted in substantially lowered incidence (3%-46%). It is concluded that these criteria for the electrodiagnostic delineation of polyneuropathy are the most sensitive to date, with respect to the early confirmation of the diagnosis of Guillain-Barré syndrome. PMID:8530930

  3. AAV1.NT-3 gene therapy attenuates spontaneous autoimmune peripheral polyneuropathy.

    PubMed

    Yalvac, M E; Arnold, W D; Braganza, C; Chen, L; Mendell, J R; Sahenk, Z

    2016-01-01

    The spontaneous autoimmune peripheral polyneuropathy (SAPP) model in B7-2 knockout non-obese diabetic mice shares clinical and histological features with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Secondary axonal loss is prominent in the progressive phase of this neuropathy. Neurotrophin 3 (NT-3) is an important autocrine factor supporting Schwann cell survival and differentiation and stimulates neurite outgrowth and myelination. The anti-inflammatory and immunomodulatory effects of NT-3 raised considerations of potential efficacy in the SAPP model that could be applicable to CIDP. For this study, scAAV1.tMCK.NT-3 was delivered to the gastrocnemius muscle of 25-week-old SAPP mice. Measurable NT-3 levels were found in the serum at 7-week postgene delivery. The outcome measures included functional, electrophysiological and histological assessments. At week 32, NT-3-treated mice showed increased hind limb grip strength that correlated with improved compound muscle action potential amplitude. Myelinated fiber density was 1.9 times higher in the NT-3-treated group compared with controls and the number of demyelinated axons was significantly lower. The remyelinated nerve fiber population was significantly increased. These improved histopathological parameters from scAAV1.tMCK.NT-3 treatment occurred in the setting of reduced sciatic nerve inflammation. Collectively, these findings suggest a translational application to CIDP. PMID:26125608

  4. Erythromelalgia-like presentation of chronic acquired demyelinating polyneuropathy in a setting of past alcohol abuse.

    PubMed

    Chuquilin, Miguel; Dhand, Upinder K

    2016-02-01

    Erythromelalgia may be primary or secondary to an underlying medical condition. Association with small fiber neuropathy and axonal large fiber peripheral neuropathy has been described. Erythromelalgia in the setting of acquired demyelinating neuropathy has not been reported. We report a 52-year-old woman with severe erythromelalgia, pain and burning, progressive weakness, hyporeflexia and distal pan-sensory deficits. Cerebrospinal fluid protein was 219 mg/dL. Nerve conduction study revealed extreme (ten-fold) prolongation of distal motor latencies, markedly slow motor nerve conduction, reduced terminal latency index, reduced distal compound muscle action potential (CMAP) amplitude, possible conduction blocks, and distal denervation. Treatment with intravenous immunoglobulin, prednisone and azathioprine resulted in marked clinical and electrophysiological improvement. Our patient fulfills the diagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP); however, the unique electrodiagnostic features and presentation with erythromelalgia may represent a CIDP variant or a novel dysimmune neuropathy, or may partly be related to neurotoxic effects of prior alcohol abuse. PMID:26804376

  5. Cardiovascular Autonomic Dysfunction Predicts Diabetic Foot Ulcers in Patients With Type 2 Diabetes Without Diabetic Polyneuropathy

    PubMed Central

    Yun, Jae-Seung; Cha, Seon-Ah; Lim, Tae-Seok; Lee, Eun-Young; Song, Ki-Ho; Ahn, Yu-Bae; Yoo, Ki-Dong; Kim, Joon-Sung; Park, Yong-Moon; Ko, Seung-Hyun

    2016-01-01

    Abstract We investigated the factors that might influence the development of diabetic foot ulcers (DFUs) in type 2 diabetes patients without diabetic polyneuropathy (DPN). From January 2000 to December 2005, a total of 595 patients who had type 2 diabetes without DPN between the ages of 25 and 75 years, and had no prior history of DFUs were consecutively enrolled in the study. A cardiovascular autonomic function test was performed to diagnose cardiovascular autonomic neuropathy (CAN) using heart rate variability parameters. The median follow-up time was 13.3 years. Among the 449 (75.4%) patients who completed the follow-up evaluation, 22 (4.9%) patients developed new ulcers, and 6 (1.3%) patients underwent the procedure for lower extremity amputations. The patients in the DFUs group had a longer duration of diabetes, higher baseline HbA1c levels, higher rates of nephropathy, and CAN. A Cox hazard regression analysis results revealed that the development of DFUs was significantly associated with the presence of CAN (normal vs definite CAN; HR, 4.45; 95% confidence interval, 1.29–15.33) after adjusting for possible confounding factors. The development of DFUs was independently associated with CAN in patients with type 2 diabetes without DPN. We suggested the importance of CAN as a predictor of DFUs even in the patients without DPN, and the need to pay attention to patients with definite CAN and type 2 diabetes. PMID:27015188

  6. Advances in the diagnosis and management of diabetic distal symmetric polyneuropathy

    PubMed Central

    2014-01-01

    Distal symmetric polyneuropathy (DSPN) is the most common chronic complication of diabetes mellitus. The pathogenesis of DSPN is not fully elucidated, but it is certainly multifactorial in nature and attributable to metabolic and microvessel disorders related to chronic hyperglycemia, diabetes duration, and several cardiovascular risk factors. Early diagnosis and appropriate management are extremely important, since up to 50% of DSPN cases may be asymptomatic, and patients are unaware of foot injury leading to foot ulcers and amputation. Simple, validated tests such as the Neuropathy Disability Score and/or Vibration Perception Threshold may be used to diagnose DSPN. Similarly, neurological dysfunction screening questionnaires should be used to assess the quality and severity of DSPN symptoms. Using both methods enables prediction of the prognosis of diabetic patients with DSPN. No causative treatment of DSPN is known, but the results of clinical trials indicate that several treatment options are highly effective in symptomatic treatment of painful DSPN. The appropriate treatment of DSPN may improve the outcome, preventing or delaying the development of numerous diabetic complications. PMID:24904671

  7. AAV1.NT-3 gene therapy attenuates spontaneous autoimmune peripheral polyneuropathy

    PubMed Central

    Yalvac, M E; Arnold, W D; Braganza, C; Chen, L; Mendell, J R; Sahenk, Z

    2016-01-01

    The spontaneous autoimmune peripheral polyneuropathy (SAPP) model in B7-2 knockout non-obese diabetic mice shares clinical and histological features with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Secondary axonal loss is prominent in the progressive phase of this neuropathy. Neurotrophin 3 (NT-3) is an important autocrine factor supporting Schwann cell survival and differentiation and stimulates neurite outgrowth and myelination. The anti-inflammatory and immunomodulatory effects of NT-3 raised considerations of potential efficacy in the SAPP model that could be applicable to CIDP. For this study, scAAV1.tMCK.NT-3 was delivered to the gastrocnemius muscle of 25-week-old SAPP mice. Measurable NT-3 levels were found in the serum at 7-week postgene delivery. The outcome measures included functional, electrophysiological and histological assessments. At week 32, NT-3-treated mice showed increased hind limb grip strength that correlated with improved compound muscle action potential amplitude. Myelinated fiber density was 1.9 times higher in the NT-3-treated group compared with controls and the number of demyelinated axons was significantly lower. The remyelinated nerve fiber population was significantly increased. These improved histopathological parameters from scAAV1.tMCK.NT-3 treatment occurred in the setting of reduced sciatic nerve inflammation. Collectively, these findings suggest a translational application to CIDP. PMID:26125608

  8. Critical illness myopathy and polyneuropathy - A challenge for physiotherapists in the intensive care units.

    PubMed

    Pattanshetty, Renu B; Gaude, Gajanan S

    2011-04-01

    The development of critical patient related generalized neuromuscular weakness, referred to as critical illness polyneuropathy (CIP) and critical illness myopathy (CIM), is a major complication in patients admitted to intensive care units (ICU). Both CIP and CIM cause muscle weakness and paresis in critically ill patients during their ICU stay. Early mobilization or kinesiotherapy have shown muscle weakness reversion in critically ill patients providing faster return to function, reducing weaning time, and length of hospitalization. Exercises in the form of passive, active, and resisted forms have proved to improve strength and psychological well being. Clinical trials using neuromuscular electrical stimulation to increase muscle mass, muscle strength and improve blood circulation to the surrounding tissue have proved beneficial. The role of electrical stimulation is unproven as yet. Recent evidence indicates no difference between treated and untreated muscles. Future research is recommended to conduct clinical trials using neuromuscular electrical stimulation, exercises, and early mobilization as a treatment protocol in larger populations of patients in ICU. PMID:21814370

  9. Isoniazid-induced polyneuropathy in a tuberculosis patient – implication for individual risk stratification with genotyping?

    PubMed Central

    Stettner, Mark; Steinberger, Daniela; Hartmann, Christian J; Pabst, Tatjana; Konta, Lidija; Hartung, Hans Peter; Kieseier, Bernd C

    2015-01-01

    Background Development of polyneuropathy (PNP) under treatment for tuberculosis (TB), including isoniazid (INH), is a highly relevant adverse drug effect. The NAT2 acetylation status is a predictor of potential toxic effects of INH. The question as to whether individual risk stratification by genotyping is useful to avoid suffering of patients and to lower costs for the health care system is of considerable clinical importance. Case Presentation After drug treatment for TB, including INH, a 23-year-old man developed severe PNP. During the treatment, laboratory results have been indicating incipient liver and renal injury. Later, molecular genetic analyses were performed and revealed a variation in the NAT2 gene and the c1/c2 genotype of the CYP2E1 gene, both described to contribute to an elevated risk for anti-tuberculostatic-induced liver damages (ATIL). Conclusion The combination of metabolizer genotypes should be taken into account as a cause for toxic effects and the development of PNP. Individual genotyping, performed before medication or at least if an elevation of liver parameters is observed, may reduce the risk of severe cases of PNP by early adjustment of treatment. Our case study indicates that evaluation of individual risk stratification with systematic pharmacogenetic genotyping of metabolizer gene combinations in the context of TB treatment should be addressed in clinical studies with larger cohorts. PMID:26355945

  10. Signs and Symptoms vs Nerve Conduction Studies to Diagnose Diabetic Sensorimotor Polyneuropathy

    PubMed Central

    2010-01-01

    Introduction Test whether physicians can validly and reproducibly diagnose diabetic sensorimotor polyneuropathy (DSPN). Methods Twelve physicians assessed 24 patients with diabetes mellitus (DM) on consecutive days (576 examinations) with physical features and voice disguised. Results were compared to gold standard 75% group diagnosis and a nerve conduction score (Σ 5 NC nds). Results Masking of patients was achieved. Reproducibility measured by the kappa coefficient and compared to Σ 5 NC nd varied considerably among physicians: median and ranges: signs 0.8 (0.32 to 1.0); symptoms 0.79 (0.36 to 1.0) and diagnoses 0.47 (0.33 to 0.84) – both low and high scores indicating poor performance. There was substantial agreement between 75% group dx and confirmed NC abnormality. As compared to Σ 5 NC, individual physicians’ clinical diagnosis was excessively variable and frequently inaccurate. Discussion Study physician diagnosis from signs and symptoms were excessively variable, often over-estimating DSPN. Specific approaches to improving proficiency should be tested. PMID:20658599

  11. Is Stem Cell Transplantation Ready for Prime Time in Diabetic Polyneuropathy?

    PubMed

    Mizukami, Hiroki; Yagihashi, Soroku

    2016-09-01

    Diabetic polyneuropathy (DPN) is the most common complication that emerges early in patients who have diabetes. Curative treatment for overt or symptomatic DPN has not been established, requiring much effort to explore new modalities. Thus, the use of various kinds of stem cells as a potential therapeutic option for DPN is of particular interest. The beneficial effects were proposed to be attributed to either cytokine released from transplanted stem cells or the differentiation of stem cells to substitute the damaged peripheral nerve. Furthermore, based on the concept that humoral factors secreted from stem cells play a pivotal role in tissue regeneration, the utilization of conditioned medium derived from the stem cell culture serves as a novel tool for regenerative therapy. However, many questions have not been yet answered to determine whether stem cell therapy is essential in clinical application of DPN. In this report, we review the current status of preclinical studies on stem cell therapy for DPN and discuss future prospects. PMID:27485630

  12. The effects of progressive-resisted exercises on muscle strength and health-related quality of life in persons with HIV-related poly-neuropathy in Zimbabwe.

    PubMed

    Mkandla, Khumbula; Myezwa, Hellen; Musenge, Eustasius

    2016-05-01

    Distal symmetrical poly-neuropathy (DSP) is a neurological complication associated with HIV/AIDS and stavudine (d4T) containing antiretroviral therapy. People with DSP experience pain, numbness and muscle weakness, which affect their quality of life (QOL). The purpose of this study was to establish the effect of a progressive-resisted exercise (PRE) intervention on health-related quality of life (HR-QOL) in people living with HIV/AIDS-related DSP. An assessor-blinded randomised controlled trial was conducted, with participants sourced from 10 clinics with HIV services, the family care clinic at Wilkins Hospital and 2 large hospitals in Harare, Zimbabwe. A 12-week PRE intervention was conducted twice weekly for 80 participants, while the control group with 80 participants continued with usual daily activities. The main outcome variable was HR-QOL for which we controlled for demographic and clinical measures in generalised estimating equation population-averaged models. Data were summarised and analysed using an intention to treat analysis approach using the Stata v10 program. Mean age of participants was 42.2 years (SD = 8.5). While d4T was used by 59% (n = 94), an equal proportion of the participants also had moderate to severe neuropathy. PRE was found to significantly improve HR-QOL in the intervention group based on the mean difference between the intervention group mean change and the mean change in the control group (F ratio 4.24; p = .04). This study established that PREs have positive effects on HR-QOL for people living with HIV/AIDS-related DSP. PMID:26729347

  13. Effect of rosuvastatin on diabetic polyneuropathy: a randomized, double-blind, placebo-controlled Phase IIa study

    PubMed Central

    Hernández-Ojeda, Jaime; Román-Pintos, Luis Miguel; Rodríguez-Carrízalez, Adolfo Daniel; Troyo-Sanromán, Rogelio; Cardona-Muñoz, Ernesto Germán; Alatorre-Carranza, María del Pilar; Miranda-Díaz, Alejandra Guillermina

    2014-01-01

    Background Diabetic neuropathy affects 50%–66% of patients with diabetes mellitus. Oxidative stress generates nerve dysfunction by causing segmental demyelinization and axonal degeneration. Antioxidants are considered to be the only etiologic management for diabetic polyneuropathy, and statins such as rosuvastatin increase nitric oxide bioavailability and reduce lipid peroxidation. The aim of this study was to evaluate the antioxidant effect of rosuvastatin in diabetic polyneuropathy. Methods We conducted a randomized, double-blind, placebo-controlled Phase IIa clinical trial in patients with type 2 diabetes and diabetic polyneuropathy (DPN) stage ≥1b. We allocated subjects to two parallel groups (1:1) that received rosuvastatin 20 mg or placebo for 12 weeks. Primary outcomes were neuropathic symptom score, disability score, and nerve conduction studies, and secondary outcomes were glycemic control, lipid and hepatic profile, lipid peroxidation, and nerve growth factor beta (NGF-β) levels. Results Both groups were of similar age and duration since diagnosis of diabetes and DPN. We observed improvement of DPN in the rosuvastatin group from stage 2a (88.2%) to stage 1b (41.2%), improvement of neuropathic symptom score from 4.5±2 to 2.4±1.8, and significant (P=0.001) reductions of peroneal nerve conduction velocity (from 40.8±2.2 to 42.1±1.6 seconds) and lipid peroxidation (from 25.4±2 to 12.2±4.0 nmol/mL), with no significant change in glycemic control or β-NGF. Conclusion The severity, symptoms, and nerve conduction parameters of DPN improved after 12 weeks of treatment with rosuvastatin. These beneficial effects appear to be attributable to reductions in lipid peroxidation and oxidative stress. PMID:25214797

  14. Rare Variants in MME, Encoding Metalloprotease Neprilysin, Are Linked to Late-Onset Autosomal-Dominant Axonal Polyneuropathies.

    PubMed

    Auer-Grumbach, Michaela; Toegel, Stefan; Schabhüttl, Maria; Weinmann, Daniela; Chiari, Catharina; Bennett, David L H; Beetz, Christian; Klein, Dennis; Andersen, Peter M; Böhme, Ilka; Fink-Puches, Regina; Gonzalez, Michael; Harms, Matthew B; Motley, William; Reilly, Mary M; Renner, Wilfried; Rudnik-Schöneborn, Sabine; Schlotter-Weigel, Beate; Themistocleous, Andreas C; Weishaupt, Jochen H; Ludolph, Albert C; Wieland, Thomas; Tao, Feifei; Abreu, Lisa; Windhager, Reinhard; Zitzelsberger, Manuela; Strom, Tim M; Walther, Thomas; Scherer, Steven S; Züchner, Stephan; Martini, Rudolf; Senderek, Jan

    2016-09-01

    Axonal polyneuropathies are a frequent cause of progressive disability in the elderly. Common etiologies comprise diabetes mellitus, paraproteinaemia, and inflammatory disorders, but often the underlying causes remain elusive. Late-onset axonal Charcot-Marie-Tooth neuropathy (CMT2) is an autosomal-dominantly inherited condition that manifests in the second half of life and is genetically largely unexplained. We assumed age-dependent penetrance of mutations in a so far unknown gene causing late-onset CMT2. We screened 51 index case subjects with late-onset CMT2 for mutations by whole-exome (WES) and Sanger sequencing and subsequently queried WES repositories for further case subjects carrying mutations in the identified candidate gene. We studied nerve pathology and tissue levels and function of the abnormal protein in order to explore consequences of the mutations. Altogether, we observed heterozygous rare loss-of-function and missense mutations in MME encoding the metalloprotease neprilysin in 19 index case subjects diagnosed with axonal polyneuropathies or neurodegenerative conditions involving the peripheral nervous system. MME mutations segregated in an autosomal-dominant fashion with age-related incomplete penetrance and some affected individuals were isolated case subjects. We also found that MME mutations resulted in strongly decreased tissue availability of neprilysin and impaired enzymatic activity. Although neprilysin is known to degrade β-amyloid, we observed no increased amyloid deposition or increased incidence of dementia in individuals with MME mutations. Detection of MME mutations is expected to increase the diagnostic yield in late-onset polyneuropathies, and it will be tempting to explore whether substances that can elevate neprilysin activity could be a rational option for treatment. PMID:27588448

  15. Therapeutic efficacy of bone marrow-derived mononuclear cells in diabetic polyneuropathy is impaired with aging or diabetes

    PubMed Central

    Kondo, Masaki; Kamiya, Hideki; Himeno, Tatsuhito; Naruse, Keiko; Nakashima, Eitaro; Watarai, Atsuko; Shibata, Taiga; Tosaki, Takahiro; Kato, Jiro; Okawa, Tetsuji; Hamada, Yoji; Isobe, Ken-ichi; Oiso, Yutaka; Nakamura, Jiro

    2015-01-01

    Aims/Introduction Recent studies have shown that cell transplantation therapies, such as endothelial precursor cells, bone marrow-derived mononuclear cells (BM-MNCs) and mesenchymal stem cells, are effective on diabetic polyneuropathy through ameliorating impaired nerve blood flow in diabetic rats. Here, we investigated the effects of BM-MNCs transplantation in diabetic polyneuropathy using BM-MNCs derived from adult (16-week-old) diabetic (AD), adult non-diabetic (AN) or young (8-week-old) non-diabetic (YN) rats. Materials and Methods BM-MNCs of AD and AN were isolated after an 8-week diabetes duration. The BM-MNCs were characterized using flow cytometry analysis of cell surface markers and reverse transcription polymerase chain reaction of several cytokines. BM-MNCs or saline were injected into hind limb muscles. Four weeks later, the thermal plantar test, nerve conduction velocity, blood flow of the sciatic nerve and capillary-to-muscle fiber ratio were evaluated. Results The number of CD29+/CD90+ cells that host mesenchymal stem cells in BM-MNCs decreased in AD compared with AN or YN, and transcript expressions of basic fibroblast growth factor and nerve growth factor in BM-MNCs decreased in AD compared with AN or YN. Impaired thermal sensation, decreased blood flow of the sciatic nerve and delayed nerve conduction velocity in 8-week-diabetic rats were significantly ameliorated by BM-MNCs derived from YN, whereas BM-MNCs from AD or AN rats did not show any beneficial effect in these functional tests. Conclusions These results show that cytokine production abilities and the mesenchymal stem cell population of BM-MNCs would be modified by aging and metabolic changes in diabetes, and that these differences could explain the disparity of the therapeutic efficacy of BM-MNCs between young and adult or diabetic and non-diabetic patients in diabetic polyneuropathy. PMID:25802721

  16. Reversible acute axonal polyneuropathy associated with Wernicke-Korsakoff syndrome: impaired physiological nerve conduction due to thiamine deficiency?

    PubMed

    Ishibashi, S; Yokota, T; Shiojiri, T; Matunaga, T; Tanaka, H; Nishina, K; Hirota, H; Inaba, A; Yamada, M; Kanda, T; Mizusawa, H

    2003-05-01

    Acute axonal polyneuropathy and Wernicke-Korsakoff encephalopathy developed simultaneously in three patients. Nerve conduction studies (NCS) detected markedly decreased compound muscle action potentials (CMAPs) and sensory nerve action potentials (SNAPs) with minimal conduction slowing; sympathetic skin responses (SSRs) were also notably decreased. Sural nerve biopsies showed only mild axonal degeneration with scattered myelin ovoid formation. The symptoms of neuropathy lessened within two weeks after an intravenous thiamine infusion. CMAPs, SNAPs, and SSRs also increased considerably. We suggest that this is a new type of peripheral nerve impairment: physiological conduction failure with minimal conduction delay due to thiamine deficiency. PMID:12700319

  17. Characterization of IgG4 anti-neurofascin 155 antibody-positive polyneuropathy

    PubMed Central

    Ogata, Hidenori; Yamasaki, Ryo; Hiwatashi, Akio; Oka, Nobuyuki; Kawamura, Nobutoshi; Matsuse, Dai; Kuwahara, Motoi; Suzuki, Hidekazu; Kusunoki, Susumu; Fujimoto, Yuichi; Ikezoe, Koji; Kishida, Hitaru; Tanaka, Fumiaki; Matsushita, Takuya; Murai, Hiroyuki; Kira, Jun-ichi

    2015-01-01

    Objective To investigate anti-neurofascin 155 (NF155) antibody-positive chronic inflammatory demyelinating polyneuropathy (CIDP). Methods Sera from 50 consecutive CIDP patients diagnosed in our clinic, 32 patients with multiple sclerosis, 40 patients with other neuropathies including 26 with Guillain–Barré syndrome (GBS)/Fisher syndrome, and 30 healthy controls were measured for anti-NF antibodies by flow cytometry using HEK293 cell lines stably expressing human NF155 or NF186. Four additional CIDP patients with anti-NF155 antibodies referred from other clinics were enrolled for clinical characterization. Results The positivity rate for anti-NF155 antibodies in CIDP patients was 18% (9/50), who all showed a predominance of IgG4 subclass. No other subjects were positive, except one GBS patient harboring IgG1 anti-NF155 antibodies. No anti-NF155 antibody carriers had anti-NF186 antibodies. Anti-NF155 antibody-positive CIDP patients had a significantly younger onset age, higher frequency of drop foot, gait disturbance, tremor and distal acquired demyelinating symmetric phenotype, greater cervical root diameter on magnetic resonance imaging neurography, higher cerebrospinal fluid protein levels, and longer distal and F-wave latencies than anti-NF155 antibody-negative patients. Marked symmetric hypertrophy of cervical and lumbosacral roots/plexuses was present in all anti-NF155 antibody-positive CIDP patients examined by neurography. Biopsied sural nerves from two patients with anti-NF155 antibodies demonstrated subperineurial edema and occasional paranodal demyelination, but no vasculitis, inflammatory cell infiltrates, or onion bulbs. Among anti-NF155 antibody-positive patients, treatment responders more frequently had daily oral corticosteroids and/or immunosuppressants in addition to intravenous immunoglobulins than nonresponders did. Interpretation Anti-NF155 antibodies occur in a subset of CIDP patients with distal-dominant involvement and symmetric nerve

  18. Polyneuropathy associated with duodenal infusion of levodopa in Parkinson's disease: features, pathogenesis and management.

    PubMed

    Uncini, Antonino; Eleopra, Roberto; Onofrj, Marco

    2015-05-01

    Patients with Parkinson's disease (PD) treated with oral levodopa have a higher prevalence of chronic, prevalently sensory, usually mild axonal polyneuropathy (PNP). Several studies showed a positive association among PNP, cumulative levodopa dosage, low serum B12 and high-homocysteine and methylmalonic acid level. Anecdotal severe acute or subacute PNPs thought to be Guillain-Barré syndrome have been reported in patients receiving continuous intraduodenal infusion of levodopa/carbidopa intestinal gel (LCIG). We report an additional acute case and by a systematic literature search we also reviewed the clinical and laboratory features of 13 other acute and 21 subacute PNP cases occurring during LCIG treatment. In series with at least nine patients, the mean frequency of acute and subacute PNP is 13.6% and the mortality rate at 6 months in acute cases is 14%. The great majority of PNP cases displayed axonal sensory-motor and reduced vitamin B12 levels, and alterations of metabolites of 1-carbon pathway were found in most patients. We discuss the possible role of high-levodopa dosage, vitamin B12, B6 and folate deficiency and accumulation of homocysteine and methylmalonic acid in the pathogenesis to conclude that there is enough, although circumstantial, evidence that alterations of 1-carbon pathway are implicated also in acute and subacute PNP during LCIG usage. There is no solid proof for a dysimmune pathogenesis and in our opinion acute, subacute and chronic PNP, either after oral levodopa or LCIG, represent a continuum. Finally, we propose recommendations for prevention and management of PNP occurring during LCIG treatment. PMID:25168395

  19. Joint preserving surgery versus arthrodesis in operative treatment of patients with neuromuscular polyneuropathy: questionnaire assessment.

    PubMed

    Napiontek, Marek; Pietrzak, Krzysztof

    2015-02-01

    The purpose of the paper was to present the results of surgical treatment of foot deformities in peripheral neuropathies using bone procedures: both joint preserving and with joint arthrodesis. The study included 26 patients, 14 males and 12 females (43 feet). The age of the patients at surgery ranged from 5 to 55 years (average 23 years). The follow-up ranged from 0.5 to 15 years (average 4.3 years). Seventeen patients presented Charcot-Marie-Tooth disease, three Friedreich's ataxia and six peripheral motor and sensory neuropathies of undetermined nature. Sixteen patients had bilateral procedures. Four patients had to be re-operated during the follow-up. The patients were divided into four groups depending on the age and the surgical technique applied. The groups I and II (9 children, 17 feet) included patients with growth plate still present in the foot just before surgery. In the groups III and IV (17 adults, 26 feet), bone growth was completed. The assessment of all patients based on a modified AOFAS scale ranged from 44 to 105 points (mean 83.7; SD 17.5). The assessment on the subjective scale ranged from 3 to 10 points (mean 7.4; SD 2.1). The assessment of quality of life on the WOMAC scale ranged from 0 to 41 points (mean 15.7; SD 13.2). All patients stated that they would decide to undergo the treatment again. For groups I and II, joint preserving surgeries gave better results; however, the results could not be statistically confirmed. The results for the groups III and IV were inconclusive as to which surgical techniques should be preferred, arthrodesis or joint preserving. The results show that none of the surgical techniques used for correction of foot deformities in motor-sensory polyneuropathies seems to be preferable. PMID:24968792

  20. An 'Importance' Map of Signs and Symptoms to Classify Diabetic Polyneuropathy: An Exploratory Data Analysis

    PubMed Central

    Sacco, Isabel C. N.; Suda, Eneida Yuri; Vigneron, Vincent; Sartor, Cristina Dallemole

    2015-01-01

    Aims/Hypothesis Early diagnosis of diabetic polyneuropathy (DPN) is critical for a good prognosis. We aimed to identify different groups of patients, based on the various common clinical signs and symptoms of DPN, that represent a progressive worsening of the disease before the onset of plantar ulceration or amputation. We also sought to identify the most important DPN-related variables that can discriminate between groups, thus representing the most informative variables for early detection. Methods In 193 diabetic patients, we assessed 16 DPN-related signs, symptoms, and foot characteristics, based on the literature and the International Consensus on the Diabetic Foot. We used multiple correspondence analysis and the Kohonen algorithm to group the variables into micro and macro-classes and to identify clusters of patients that represent different DPN conditions. Results Four distinct groups were observed. One group showed no indication of DPN. The remaining groups were characterized by a progressive loss of the vibration perception, without a worsening of symptoms or tactile perception. The 2 intermediate groups presented different aspects of DPN: one showed mostly DPN symptoms and the other showed the incipient vibration impairment, callus and crack formation, and foot arch alteration. The fourth group showed more severe foot and DPN conditions, including ulceration and amputation, absence of vibration and tactile perception (irrespective of how many compromised foot areas), and worse foot deformities and callus and crack formation. Conclusion Vibration perception was more informative than tactile sensitivity in discriminating early DPN onset because its impairment was evident in more groups. Symptoms and callus and cracks did not discriminate the severity status and should be interpreted in association with other clinical variables. Reconsideration of the current screening techniques is needed to clinically determine the early onset of neuropathy using tactile

  1. From treatment to preventive actions: improving function in patients with diabetic polyneuropathy.

    PubMed

    Sacco, Isabel C N; Sartor, Cristina D

    2016-01-01

    Diabetic polyneuropathy is an insidious and long-term complication of this disease. Synergistic treatments and preventive actions are crucial because there are no clear boundaries for determining when health professionals should intervene or what intervention would best avoid the consequences of neuropathy. Until now, most therapies to any diabetic individual were applied only after the patient's limb was ulcerated or amputated. The loss of muscle and joint functions is recognized as the main cause of plantar overloading. However, if foot and ankle exercises are performed following the early diagnosis of diabetes, they can enable the patient to maintain sufficient residual function to interact with the environment. This article summarizes the current knowledge about the musculoskeletal deficits and biomechanical alterations caused by neuropathy. It also describes the potential benefits of foot and ankle exercises for any diabetic patient that is not undergoing the plantar ulcer healing process. We concentrate on the prevention of the long-term deficits of neuropathy. We also discuss the main strategies and protocols of therapeutic exercises for joints and muscles with deficits, which are applicable to all diabetic patients with mild to moderate neuropathy. We describe further efforts in exploiting the applicability of assistive technologies to improve the adherence to an exercise program. Following the contemporary trends towards self-monitoring and self-care, we developed a software to monitor and promote personalized exercises with the aim of improving autonomous performance in daily living tasks. Initiatives to prevent the complications of functional diabetes are highly recommended before it is too late for the patient and there is no longer an opportunity to reverse the tragic consequences of neuropathy progression. PMID:26452065

  2. Evidence of Small-Fiber Polyneuropathy in Unexplained, Juvenile-Onset, Widespread Pain Syndromes

    PubMed Central

    Klein, Max M.

    2013-01-01

    OBJECTIVE: We tested the hypothesis that acquired small-fiber polyneuropathy (SFPN), previously uncharacterized in children, contributes to unexplained pediatric widespread pain syndromes. METHODS: Forty-one consecutive patients evaluated for unexplained widespread pain beginning before age 21 had medical records comprehensively analyzed regarding objective diagnostic testing for SFPN (neurodiagnostic skin biopsy, nerve biopsy, and autonomic function testing), plus histories, symptoms, signs, other tests, and treatments. Healthy, demographically matched volunteers provided normal controls for SFPN tests. RESULTS: Age at illness onset averaged 12.3 ± 5.7 years; 73% among this poly-ethnic sample were female (P = .001). Sixty-eight percent were chronically disabled, and 68% had hospitalizations. Objective testing diagnosed definite SFPN in 59%, probable SFPN in 17%, and possible SFPN in 22%. Only 1 of 41 had entirely normal SFPN test results. Ninety-eight percent of patients had other somatic complaints consistent with SFPN dysautonomia (90% cardiovascular, 82% gastrointestinal, and 34% urologic), 83% reported chronic fatigue, and 63% had chronic headache. Neurologic examinations identified reduced sensation in 68% and vasomotor abnormalities in 55%, including 23% with erythromelalgia. Exhaustive investigations for SFPN causality identified only history of autoimmune illnesses in 33% and serologic markers of disordered immunity in 89%. Treatment with corticosteroids and/or intravenous immune globulin objectively and subjectively benefited 80% of patients (12/15). CONCLUSIONS: More than half among a large series of patients with childhood-onset, unexplained chronic widespread pain met rigorous, multitest, diagnostic criteria for SFPN, which extends the age range of acquired SFPN into early childhood. Some cases appeared immune-mediated and improved with immunomodulatory therapies. PMID:23478869

  3. Two siblings diagnosed to have transthyretin-related familial amyloid cardiomyopathy around the same time at different hospitals.

    PubMed

    Miyamura, Masatoshi; Terasaki, Fumio; Ishibashi, Kazuya; Shimazaki, Chihiro; Kimura, Fumiharu; Kuwabara, Hiroko; Tsuji, Motomu; Shibayama, Yuro; Sekijima, Yoshiki; Tojo, Kana; Ishizaka, Nobukazu

    2012-01-01

    Mutation in the transthyretin (TTR) gene may clinically manifest as cardiomyopathy. Here, we describe 69-year-old and 72-year-old brothers who were diagnosed as having TTR-related familial amyloid cardiomyopathy by endomyocardial biopsy at different hospitals at around the same time. They were not from an endemic area of familial amyloid polyneuropathy. Genetic analysis showed a base change in the TTR gene leading to a p.Val30Met mutation in both patients. Screening of family members, as well as detailed family history taking, is important for the diagnosis of cardiomyopathy of unknown etiology. PMID:22382560

  4. Autoantibody-Mediated Sensory Polyneuropathy Associated with Indolent B-Cell Non-Hodgkin's Lymphoma: A Report of Two Cases

    PubMed Central

    2015-01-01

    Background and Purpose Abnormalities of the peripheral nervous system occur in 5% of patients with lymphoma. Polyneuropathy has not been described in patients with mantle-cell and marginal-zone B-cell lymphomas. Case Report Two elderly patients with indolent non-Hodgkin's lymphoma developed a progressive sensory polyneuropathy that was associated with serum autoantibodies directed against asialosyl/sialosyl gangliosides and myelin-associated glycoprotein/sulfated glucuronyl paragloboside, respectively, which are peripheral-nerve antigens. The oligoclonal pattern of these antibodies hinted at a lymphoma-induced immune dysregulation. The neuropathy stabilized clinically during treatment with intravenous immunoglobulin G. B-cell lymphoma was managed with a "watchful waiting" approach. Conclusions The concept of antigen-specific, immune-mediated neuropathy associated with slow-growing lymphoma of mature B-cells may be underrecognized. The principle of treating the illness underlying neuropathy may not be always indicated or necessary if risk-benefit and cost-benefit analyses are taken into account. PMID:25749823

  5. Polyneuropathy and dementia in old age: common inflammatory and vascular parameters.

    PubMed

    Leblhuber, Friedrich; Schroecksnadel, Katharina; Beran-Praher, Margit; Haller, Herbert; Steiner, Kostja; Fuchs, Dietmar

    2011-05-01

    Thirty-three inpatients (22 females, 11 males, aged 79.4 ± 9.5 years) were investigated in this prospective cohort study to study the prevalence of polyneuropathy (PNP) and dementia in geriatric inpatients. Clinical and electrodiagnostic investigations, routine laboratory, including thyroid parameters, folic acid, vitamin B(12), homocysteine, neopterin, fibrinogen and glycosylated hemoglobin were measured in serum, the mini-mental state examination and computed tomographic scanning were performed in each patient. PNP was found clinically and electrodiagnostically in 96% of patients. Age was the most precipitating factor for PNP, and was significantly correlated to electrodiagnostic changes in the nerves investigated in both, upper and lower extremities, while clinical symptoms were confined only to the feet. Correlation was seen between homocysteine and the amplitude of the sural nerve (surAmpl) (rs = -0.406, p = 0.029) as well as the sural nerve conduction velocity (surNCV) (rs = -0.389, p = 0.037), and between neopterin and the grade of denervation (rs = 0.445, p = 0.014) in our patients. Neopterin and fibrinogen did not correlate significantly, but there was a trend to higher fibrinogen concentrations in patients with higher neopterin levels (rs = 0.344, p = 0.062). A trend of a correlation was seen between higher homocysteine concentrations and the number of changes in electrodiagnostic measurements (rs = 0.354, p = 0.055). Twenty-one of the 33 patients (64%) were demented, 9 (27%) presented clinically as mild cognitive impairment, 3 (9%) were not demented. Vascular risk factors were found in 83%: hypertension in 58%, hypercholesterinemia in 39%, cardiac disease in 36%, diabetes mellitus (DM) in 21%, peripheral arterial disease (PAD) in 9%. A significant correlation was found between homocysteine and folic acid concentrations (rs = -0.401, p = 0.028). Falls were reported in 48% of cases, indicating PNP as a risk factor in this group of patients. In conclusion

  6. Family Preservation & Family Functioning.

    ERIC Educational Resources Information Center

    McCroskey, Jacquelyn; Meezan, William

    This book reports a study of the outcomes of home-based family preservation services for abusive and neglectful families in Los Angeles County. Using the Family Assessment Form, the research project evaluated services provided by two voluntary agencies, and focused on changes in family functioning between the opening and closing of services during…

  7. Treatment with α-Lipoic Acid over 16 Weeks in Type 2 Diabetic Patients with Symptomatic Polyneuropathy Who Responded to Initial 4-Week High-Dose Loading

    PubMed Central

    Garcia-Alcala, Hector; Santos Vichido, Celia Isabel; Islas Macedo, Silverio; Genestier-Tamborero, Christelle Nathalie; Minutti-Palacios, Marissa; Hirales Tamez, Omara; García, Carlos; Ziegler, Dan

    2015-01-01

    Effective treatment of diabetic sensorimotor polyneuropathy remains a challenge. To assess the efficacy and safety of α-lipoic acid (ALA) over 20 weeks, we conducted a multicenter randomized withdrawal open-label study, in which 45 patients with type 2 diabetes and symptomatic polyneuropathy were initially treated with ALA (600 mg tid) for 4 weeks (phase 1). Subsequently, responders were randomized to receive ALA (600 mg qd; n = 16) or to ALA withdrawal (n = 17) for 16 weeks (phase 2). During phase 1, the Total Symptom Score (TSS) decreased from 8.9 ± 1.8 points to 3.46 ± 2.0 points. During phase 2, TSS improved from 3.7 ± 1.9 points to 2.5 ± 2.5 points in the ALA treated group (p < 0.05) and remained unchanged in the ALA withdrawal group. The use of analgesic rescue medication was higher in the ALA withdrawal group than ALA treated group (p < 0.05). In conclusion, in type 2 diabetic patients with symptomatic polyneuropathy who responded to initial 4-week high-dose (600 mg tid) administration of ALA, subsequent treatment with ALA (600 mg qd) over 16 weeks improved neuropathic symptoms, whereas ALA withdrawal was associated with a higher use of rescue analgesic drugs. This trial is registered with ClinicalTrials.gov Identifier: NCT02439879. PMID:26345602

  8. Treatment with α-Lipoic Acid over 16 Weeks in Type 2 Diabetic Patients with Symptomatic Polyneuropathy Who Responded to Initial 4-Week High-Dose Loading.

    PubMed

    Garcia-Alcala, Hector; Santos Vichido, Celia Isabel; Islas Macedo, Silverio; Genestier-Tamborero, Christelle Nathalie; Minutti-Palacios, Marissa; Hirales Tamez, Omara; García, Carlos; Ziegler, Dan

    2015-01-01

    Effective treatment of diabetic sensorimotor polyneuropathy remains a challenge. To assess the efficacy and safety of α-lipoic acid (ALA) over 20 weeks, we conducted a multicenter randomized withdrawal open-label study, in which 45 patients with type 2 diabetes and symptomatic polyneuropathy were initially treated with ALA (600 mg tid) for 4 weeks (phase 1). Subsequently, responders were randomized to receive ALA (600 mg qd; n = 16) or to ALA withdrawal (n = 17) for 16 weeks (phase 2). During phase 1, the Total Symptom Score (TSS) decreased from 8.9 ± 1.8 points to 3.46 ± 2.0 points. During phase 2, TSS improved from 3.7 ± 1.9 points to 2.5 ± 2.5 points in the ALA treated group (p < 0.05) and remained unchanged in the ALA withdrawal group. The use of analgesic rescue medication was higher in the ALA withdrawal group than ALA treated group (p < 0.05). In conclusion, in type 2 diabetic patients with symptomatic polyneuropathy who responded to initial 4-week high-dose (600 mg tid) administration of ALA, subsequent treatment with ALA (600 mg qd) over 16 weeks improved neuropathic symptoms, whereas ALA withdrawal was associated with a higher use of rescue analgesic drugs. This trial is registered with ClinicalTrials.gov Identifier: NCT02439879. PMID:26345602

  9. A Gly98Val mutation in the N-Myc downstream regulated gene 1 (NDRG1) in Alaskan Malamutes with polyneuropathy.

    PubMed

    Bruun, Camilla S; Jäderlund, Karin H; Berendt, Mette; Jensen, Kristine B; Spodsberg, Eva H; Gredal, Hanne; Shelton, G Diane; Mickelson, James R; Minor, Katie M; Lohi, Hannes; Bjerkås, Inge; Stigen, Oyvind; Espenes, Arild; Rohdin, Cecilia; Edlund, Rebecca; Ohlsson, Jennie; Cizinauskas, Sigitas; Leifsson, Páll S; Drögemüller, Cord; Moe, Lars; Cirera, Susanna; Fredholm, Merete

    2013-01-01

    The first cases of early-onset progressive polyneuropathy appeared in the Alaskan Malamute population in Norway in the late 1970s. Affected dogs were of both sexes and were ambulatory paraparetic, progressing to non-ambulatory tetraparesis. On neurologic examination, affected dogs displayed predominantly laryngeal paresis, decreased postural reactions, decreased spinal reflexes and muscle atrophy. The disease was considered eradicated through breeding programmes but recently new cases have occurred in the Nordic countries and the USA. The N-myc downstream-regulated gene (NDRG1) is implicated in neuropathies with comparable symptoms or clinical signs both in humans and in Greyhound dogs. This gene was therefore considered a candidate gene for the polyneuropathy in Alaskan Malamutes. The coding sequence of the NDRG1 gene derived from one healthy and one affected Alaskan Malamute revealed a non-synonymous G>T mutation in exon 4 in the affected dog that causes a Gly98Val amino acid substitution. This substitution was categorized to be "probably damaging" to the protein function by PolyPhen2 (score: 1.000). Subsequently, 102 Alaskan Malamutes from the Nordic countries and the USA known to be either affected (n = 22), obligate carriers (n = 7) or healthy (n = 73) were genotyped for the SNP using TaqMan. All affected dogs had the T/T genotype, the obligate carriers had the G/T genotype and the healthy dogs had the G/G genotype except for 13 who had the G/T genotype. A protein alignment showed that residue 98 is conserved in mammals and also that the entire NDRG1 protein is highly conserved (94.7%) in mammals. We conclude that the G>T substitution is most likely the mutation that causes polyneuropathy in Alaskan Malamutes. Our characterization of a novel candidate causative mutation for polyneuropathy offers a new canine model that can provide further insight into pathobiology and therapy of human polyneuropathy. Furthermore, selection against this mutation can

  10. Soft-tissue uptake of 99mTc-diphosphonate and 99mTc-pyrophosphate in amyloidosis.

    PubMed

    Janssen, S; Piers, D A; van Rijswijk, M H; Meijer, S; Mandema, E

    1990-01-01

    This study describes the results of scintigraphy with 99mTc-labeled methylene-diphosphonate (99mTc-MDP) and pyrophosphate (99mTc-PYP) as a noninvasive test for the distribution of organ involvement in five different types of amyloidosis. Scintigraphy with 99mTc-labeled phosphates appeared to be a sensitive noninvasive screening test for the extent and the distribution of organ involvement in systemic AA and systemic AL amyloidosis as well as in local bronchial amyloid, local dermal amyloid, and familial amyloidotic polyneuropathy. Echocardiography, however, was more sensitive for demonstrating cardiac involvement in systemic amyloidosis than 99mTc-MDP or 99mTc-PYP scintigraphy. 99mTc-MDP images showed a better contrast than 99mTc-PYP images, although there was no difference in the extent or the intensity of soft-tissue uptake. PMID:2166666

  11. Guideline of transthyretin-related hereditary amyloidosis for clinicians.

    PubMed

    Ando, Yukio; Coelho, Teresa; Berk, John L; Cruz, Márcia Waddington; Ericzon, Bo-Göran; Ikeda, Shu-ichi; Lewis, W David; Obici, Laura; Planté-Bordeneuve, Violaine; Rapezzi, Claudio; Said, Gerard; Salvi, Fabrizio

    2013-01-01

    Transthyretin amyloidosis is a progressive and eventually fatal disease primarily characterized by sensory, motor, and autonomic neuropathy and/or cardiomyopathy. Given its phenotypic unpredictability and variability, transthyretin amyloidosis can be difficult to recognize and manage. Misdiagnosis is common, and patients may wait several years before accurate diagnosis, risking additional significant irreversible deterioration. This article aims to help physicians better understand transthyretin amyloidosis--and, specifically, familial amyloidotic polyneuropathy--so they can recognize and manage the disease more easily and discuss it with their patients. We provide guidance on making a definitive diagnosis, explain methods for disease staging and evaluation of disease progression, and discuss symptom mitigation and treatment strategies, including liver transplant and several pharmacotherapies that have shown promise in clinical trials. PMID:23425518

  12. Comparative Clustering of Plantar Pressure Distributions in Diabetics with Polyneuropathy May Be Applied to Reveal Inappropriate Biomechanical Stress

    PubMed Central

    Niemann, Uli; Spiliopoulou, Myra; Szczepanski, Thorsten; Samland, Fred; Grützner, Jens; Senk, Dominik; Ming, Antao; Kellersmann, Juliane; Malanowski, Jan; Klose, Silke; Mertens, Peter R.

    2016-01-01

    In diabetic patients, excessive peak plantar pressure has been identified as major risk factor for ulceration. Analyzing plantar pressure distributions potentially improves the identification of patients with a high risk for foot ulceration development. The goal of this study was to classify regional plantar pressure distributions. By means of a sensor-equipped insole, pressure recordings of healthy controls (n = 18) and diabetics with severe polyneuropathy (n = 25) were captured across eight foot regions. The study involved a controlled experimental protocol with multiple sessions, where a session contained several cycles of pressure exposure. Clustering was used to identify subgroups of study participants that are characterized by similar pressure distributions. For both analyzed groups, the number of clusters to best describe the pressure profiles was four. When both groups were combined, analysis again led to four distinct clusters. While three clusters did not separate between healthy and diabetic volunteers the fourth cluster was only represented by diabetics. Here the pressure distribution pattern is characterized by a focal point of pressure application on the forefoot and low pressure on the lateral region. Our data suggest that pressure clustering is a feasible means to identify inappropriate biomechanical plantar stress. PMID:27529421

  13. Acute paretic syndrome in juvenile White Leghorn chickens resembles late stages of acute inflammatory demyelinating polyneuropathies in humans

    PubMed Central

    2010-01-01

    Background Sudden limb paresis is a common problem in White Leghorn flocks, affecting about 1% of the chicken population before achievement of sexual maturity. Previously, a similar clinical syndrome has been reported as being caused by inflammatory demyelination of peripheral nerve fibres. Here, we investigated in detail the immunopathology of this paretic syndrome and its possible resemblance to human neuropathies. Methods Neurologically affected chickens and control animals from one single flock underwent clinical and neuropathological examination. Peripheral nervous system (PNS) alterations were characterised using standard morphological techniques, including nerve fibre teasing and transmission electron microscopy. Infiltrating cells were phenotyped immunohistologically and quantified by flow cytometry. The cytokine expression pattern was assessed by quantitative real-time PCR (qRT-PCR). These investigations were accomplished by MHC genotyping and a PCR screen for Marek's disease virus (MDV). Results Spontaneous paresis of White Leghorns is caused by cell-mediated, inflammatory demyelination affecting multiple cranial and spinal nerves and nerve roots with a proximodistal tapering. Clinical manifestation coincides with the employment of humoral immune mechanisms, enrolling plasma cell recruitment, deposition of myelin-bound IgG and antibody-dependent macrophageal myelin-stripping. Disease development was significantly linked to a 539 bp microsatellite in MHC locus LEI0258. An aetiological role for MDV was excluded. Conclusions The paretic phase of avian inflammatory demyelinating polyradiculoneuritis immunobiologically resembles the late-acute disease stages of human acute inflammatory demyelinating polyneuropathy, and is characterised by a Th1-to-Th2 shift. PMID:20109187

  14. Adult-onset painful axonal polyneuropathy caused by a dominant NAGLU mutation

    PubMed Central

    Tétreault, Martine; Gonzalez, Michael; Dicaire, Marie-Josée; Allard, Pierre; Gehring, Kalle; Leblanc, Diane; Leclerc, Nadine; Schondorf, Ronald; Mathieu, Jean; Zuchner, Stephan

    2015-01-01

    Late-onset painful sensory neuropathies are usually acquired conditions associated with common diseases. Adult presentations of known hereditary forms are often accompanied by other organ involvement. We recruited a large French-Canadian family with a dominantly inherited late-onset painful sensory neuropathy. The main clinical feature is recurrent leg pain that progresses to constant painful paraesthesias in the feet and later the hands. As it evolves, some patients develop a mild sensory ataxia. We selected four affected individuals for whole exome sequencing. Analysis of rare variants shared by all cases led to a list of four candidate variants. Segregation analysis in all 45 recruited individuals has shown that only the p.Ile403Thr variant in the α-N-acetyl-glucosaminidase (NAGLU) gene segregates with the disease. Recessive NAGLU mutations cause the severe childhood lysosomal disease mucopolysacharidosis IIIB. Family members carrying the mutation showed a significant decrease of the enzymatic function (average 45%). The late-onset and variable severity of the symptoms may have precluded the description of such symptoms in parents of mucopolysaccharidosis IIIB cases. The identification of a dominant phenotype associated with a NAGLU mutation supports that some carriers of lysosomal enzyme mutations may develop later in life much milder phenotypes. PMID:25818867

  15. Severe chronic sensory-motor polyneuropathy: coexistence of 3 unrelated etiologies in a type 1 diabetic patient. A case report and review of the literature.

    PubMed

    Micco, Andrea; Nobile-Orazio, Eduardo; Baron, Pierluigi; Conti, Giancarlo; Napoli, Laura; Serafini, Massimo; Scarlato, Guglielmo; Scarpini, Elio

    2003-03-01

    We present the case of a 58-year-old man, who has suffered from type 1 diabetes mellitus since he was young. He had monoclonal IgM kappa gammopathy of undetermined significance and high anti-MAG antibody titer. He developed a polyneuropathic picture with the clinical and laboratory features of chronic inflammatory demyelinating polyneuropathy within the span of approximately 2 years. He benefited from IV administration of high doses of immunoglobulins. Investigation of all parameters, but particularly of the clinical phenotype, can lead to a better definition of the polyneuropathic picture, especially for therapeutic and prognostic purposes. PMID:12678551

  16. Conducting processes in simulated chronic inflammatory demyelinating polyneuropathy at 20°C-42°C.

    PubMed

    Stephanova, D I; Daskalova, M; Mladenov, M

    2015-03-01

    Decreased conducting processes leading usually to conduction block and increased weakness of limbs during cold (cold paresis) or warmth (heat paresis) have been reported in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). To explore the mechanisms of these symptoms, the effects of temperature (from 20°C to 42°C) on nodal action potentials and their current kinetics in previously simulated case of 70% CIDP are investigated, using our temperature dependent multi-layered model of the myelinated human motor nerve fiber. The results show that potential amplitudes have a bifid form at 20°C. As in the normal case, for the CIDP case, the nodal action potentials are determined mainly by the nodal sodium currents (I Na ) for the temperature range of 20-39°C, as the contribution of nodal fast and slow potassium currents (I Kf and I Ks ) to the total ionic current (Ii) is negligible. Also, the contribution of I Kf and I Ks to the membrane repolarization is enhanced at temperatures higher than 39°C. However, in the temperature range of 20-42°C, all potential parameters in the CIDP case, except for the conduction block during hyperthermia (≥ 40°C) which is again at 45°C, worsen: (i) conduction velocities and potential amplitudes are decreased; (ii) afterpotentials and threshold stimulus currents for the potential generation are increased; (iii) the current kinetics of action potentials is slowed and (iv) the conduction block during hypothermia (≤ 25°C) is at temperatures lower than 20°C. These potential parameters are more altered during hyperthermia and are most altered during hypothermia. The present results suggest that the conducting processes in patients with CIDP are in higher risk during hypothermia than hyperthermia. PMID:25597276

  17. A diagnosis challenge-L4 nerve root compression as the initial presentation of chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Cojocaru, Inimioara Mihaela; Alexianu, Marilena; Bastian, Alexandra; Sapira, Violeta; Herţea, Cristina; Cojocaru, M

    2012-01-01

    The authors present the case of a 65-year-old woman who was admitted for paraparesis and paresthesias in the inferior limbs. The neurological examination revealed the difficulty in extension of the right foot and of the right toe, accompanied by paresthesias located in the anterolateral area of the right leg, dorsum and plantar area of the foot, the reduction of the right knee jerk, and of the ankle tendon jerk both sides. The vertebro-spinal MRI showed lumbar canal stenosis with L4 intraforaminal compression on the right, and L2-L3 on the left. CSF examination revealed mild increase in protein concentration. The morphological picture of the sural nerve biopsy was compatible with a chronic inflammatory neuropathy and severe muscular lesions of neurogenic origin were observed on right gastrocnemius muscle biopsy. The diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) was established. Solu-medrol (0.5 g/d)-5 days, then medrol (prednisolone) was done, followed by improving of the symptomatology. For the relapse of the disease intravenous immunoglobulins (IVIG)-0.4 g/kg/d-5 days was the elective treatment. Six months later she presented a new relapse. IVIG were administered with the remission of the sensitive symptoms. A chronic treatment with medrol was recommended. The diagnosis of L4 disc herniation was obvious in the studied case, but the electroneurographic examination brought extra data for the associated diagnosis of CIDP whose onset was asymmetrical and initially paucisymptomatic. Neither the electroneurographic examination nor the CSF examination were total relevant for CIDP, imposing the sural nerve biopsy. The diagnosis of CIDP involves a team-work composed of neurologist, electroneurophysiologist and neuropathologist. PMID:23610977

  18. Multifocal Motor Neuropathy, Multifocal Acquired Demyelinating Sensory and Motor Neuropathy and Other Chronic Acquired Demyelinating Polyneuropathy Variants

    PubMed Central

    Barohn, Richard J.; Katz, Jonathan

    2014-01-01

    Chronic acquired demyelinating neuropathies (CADP) are an important group of immune neuromuscular disorders affecting myelin. These are distinct from chronic inflammatory demyelinating polyneuropathy (CIDP). Classically, CIDP is characterized by proximal and distal weakness, large fiber sensory loss, elevated cerebrospinal fluid (CSF) protein content, demyelinating changes nerve conduction studies or nerve biopsy, and response to immunomodulating treatment. In this chapter we discuss CADP with emphasis on multifocal motor neuropathy (MMN), multifocal acquired demyelinating sensory and motor neuropathy (MADSAM), distal acquired demyelinating symmetric (DADS) neuropathy and conclude with less common variants. While each of these entities has distinctive laboratory and electrodiagnostic features that aid in their diagnosis, clinical characteristics are of paramount importance in diagnosing specific conditions and determining the most appropriate therapies. Unlike CIDP, MMN is typically asymmetric and affects only the motor nerve fibers. MMN is a rare disease that presents chronically, over several years of progression affecting the arms are more commonly than the legs. Men are more likely than women to develop MMN. MADSAM should be suspected in patients who have weakness and loss of sensation in primarily one arm or leg which progresses slowly over several months to years. It is important in patient with multifocal demyelinating clinical presentation to distinguish MMN from MADSAM since corticosteroids are not effective in MMN where the mainstay of therapy is intravenous gammaglobulin (IVIg). DADS can be subdivided into DADS-M (associated woth M-protein) and DADS-I which is idioapthic. While DADS-I patients respond somewhat to immunotherapy, DADS-M patients present with distal predominant sensorimotor demyelinating neuropathy phenotype and are notoriously refractory to immunotherapies regardless of antibodies to myelin-associated glycoprotein (MAG). Our knowledge

  19. Comparative analysis of the effects combined physical procedures and alpha-lipoic acid on the electroneurographic parameters of patients with distal sensorimotor diabetic polyneuropathy

    PubMed Central

    Grbovic, Vesna; Jurisic-Skevin, Aleksandra; Djukic, Svetlana; Stefanović, Srdjan; Nurkovic, Jasmin

    2016-01-01

    [Purpose] Painful diabetic polyneuropathy occurs as a complication in 16% of all patients with diabetes mellitus. [Subjects and Methods] A clinical, prospective open-label randomized intervention study was conducted of 60 adult patients, with distal sensorimotor diabetic neuropathy two groups of 30 patients, with diabetes mellitus type 2 with distal sensorimotor diabetic neuropathy. Patients in group A were treated with combined physical procedures, and patients in group B were treated with alpha lipoic acid. [Results] There where a statistically significant improvements in terminal latency and the amplitude of the action potential in group A patients, while group B patients showed a statistically significant improvements in conduction velocity and terminal latency of n. peroneus. Group A patients showed a statistically significant improvements in conduction velocity and terminal latency, while group B patients also showed a statistically significant improvements in conduction velocity and terminal latency. This was reflected in a significant improvements in electrophysiological parameters (conduction velocity, amplitude and latency) of the motor and sensory nerves (n. peroneus, n. suralis). [Conclusion] These results present further evidence justifying of the use of physical agents in the treatment of diabetic sensorimotor polyneuropathy. PMID:27065527

  20. Progressive Lower Extremity Weakness and Axonal Sensorimotor Polyneuropathy from a Mutation in KIF5A (c.611G>A;p.Arg204Gln)

    PubMed Central

    Jerath, Nivedita U.; Grider, Tiffany; Shy, Michael E.

    2015-01-01

    Introduction. Hereditary Spastic Paraplegia (HSP) is a rare hereditary disorder that primarily involves progressive spasticity of the legs (hamstrings, quadriceps, and calves). Methods. A 27-year-old gentleman was a fast runner and able to play soccer until age 9 when he developed slowly progressive weakness. He was wheelchair-bound by age 25. He was evaluated by laboratory testing, imaging, electrodiagnostics, and molecular genetics. Results. Electrodiagnostic testing revealed an axonal sensorimotor polyneuropathy. Genetic testing for HSP in 2003 was negative; repeat testing in 2013 revealed a mutation in KIF5A (c.611G>A;p.Arg204Gln). Conclusions. A recent advance in neurogenetics has allowed for more genes and mutations to be identified; over 76 different genetic loci for HSP and 59 gene products are currently known. Even though our patient had a sensorimotor polyneuropathy on electrodiagnostic testing and a 2003 HSP genetic panel that was negative, a repeat HSP genetic panel was performed in 2013 due to the advancement in neurogenetics. This revealed a mutation in KIF5A. PMID:26543653

  1. Comparative analysis of the effects combined physical procedures and alpha-lipoic acid on the electroneurographic parameters of patients with distal sensorimotor diabetic polyneuropathy.

    PubMed

    Grbovic, Vesna; Jurisic-Skevin, Aleksandra; Djukic, Svetlana; Stefanović, Srdjan; Nurkovic, Jasmin

    2016-01-01

    [Purpose] Painful diabetic polyneuropathy occurs as a complication in 16% of all patients with diabetes mellitus. [Subjects and Methods] A clinical, prospective open-label randomized intervention study was conducted of 60 adult patients, with distal sensorimotor diabetic neuropathy two groups of 30 patients, with diabetes mellitus type 2 with distal sensorimotor diabetic neuropathy. Patients in group A were treated with combined physical procedures, and patients in group B were treated with alpha lipoic acid. [Results] There where a statistically significant improvements in terminal latency and the amplitude of the action potential in group A patients, while group B patients showed a statistically significant improvements in conduction velocity and terminal latency of n. peroneus. Group A patients showed a statistically significant improvements in conduction velocity and terminal latency, while group B patients also showed a statistically significant improvements in conduction velocity and terminal latency. This was reflected in a significant improvements in electrophysiological parameters (conduction velocity, amplitude and latency) of the motor and sensory nerves (n. peroneus, n. suralis). [Conclusion] These results present further evidence justifying of the use of physical agents in the treatment of diabetic sensorimotor polyneuropathy. PMID:27065527

  2. Reproducibility of In Vivo Corneal Confocal Microscopy Using an Automated Analysis Program for Detection of Diabetic Sensorimotor Polyneuropathy

    PubMed Central

    Ostrovski, Ilia; Lovblom, Leif E.; Farooqi, Mohammed A.; Scarr, Daniel; Boulet, Genevieve; Hertz, Paul; Wu, Tong; Halpern, Elise M.; Ngo, Mylan; Ng, Eduardo; Orszag, Andrej; Bril, Vera; Perkins, Bruce A.

    2015-01-01

    Objective In vivo Corneal Confocal Microscopy (IVCCM) is a validated, non-invasive test for diabetic sensorimotor polyneuropathy (DSP) detection, but its utility is limited by the image analysis time and expertise required. We aimed to determine the inter- and intra-observer reproducibility of a novel automated analysis program compared to manual analysis. Methods In a cross-sectional diagnostic study, 20 non-diabetes controls (mean age 41.4±17.3y, HbA1c 5.5±0.4%) and 26 participants with type 1 diabetes (42.8±16.9y, 8.0±1.9%) underwent two separate IVCCM examinations by one observer and a third by an independent observer. Along with nerve density and branch density, corneal nerve fibre length (CNFL) was obtained by manual analysis (CNFLMANUAL), a protocol in which images were manually selected for automated analysis (CNFLSEMI-AUTOMATED), and one in which selection and analysis were performed electronically (CNFLFULLY-AUTOMATED). Reproducibility of each protocol was determined using intraclass correlation coefficients (ICC) and, as a secondary objective, the method of Bland and Altman was used to explore agreement between protocols. Results Mean CNFLManual was 16.7±4.0, 13.9±4.2 mm/mm2 for non-diabetes controls and diabetes participants, while CNFLSemi-Automated was 10.2±3.3, 8.6±3.0 mm/mm2 and CNFLFully-Automated was 12.5±2.8, 10.9 ± 2.9 mm/mm2. Inter-observer ICC and 95% confidence intervals (95%CI) were 0.73(0.56, 0.84), 0.75(0.59, 0.85), and 0.78(0.63, 0.87), respectively (p = NS for all comparisons). Intra-observer ICC and 95%CI were 0.72(0.55, 0.83), 0.74(0.57, 0.85), and 0.84(0.73, 0.91), respectively (p<0.05 for CNFLFully-Automated compared to others). The other IVCCM parameters had substantially lower ICC compared to those for CNFL. CNFLSemi-Automated and CNFLFully-Automated underestimated CNFLManual by mean and 95%CI of 35.1(-4.5, 67.5)% and 21.0(-21.6, 46.1)%, respectively. Conclusions Despite an apparent measurement (underestimation) bias in

  3. Family Meals

    MedlinePlus

    ... Story" 5 Things to Know About Zika & Pregnancy Family Meals KidsHealth > For Parents > Family Meals Print A ... even more important as kids get older. Making Family Meals Happen It can be a big challenge ...

  4. Family History

    MedlinePlus

    Your family history includes health information about you and your close relatives. Families have many factors in common, including their genes, ... as heart disease, stroke, and cancer. Having a family member with a disease raises your risk, but ...

  5. Family Arguments

    MedlinePlus

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Life Listen Español Text Size Email Print Share Family Arguments Page Content Article Body We seem to ...

  6. Family Folklore

    ERIC Educational Resources Information Center

    Kotkin, Amy J.; Baker, Holly C.

    1977-01-01

    Discusses the Family Folklore Program of the Smithsonian Institution's annual Festival of American Folklife, in which the whole family can be involved in tracing family history through story telling, photographs, etc. (MS)

  7. Family History

    MedlinePlus

    ... CDC Cancel Submit Search The CDC Family Health History Note: Javascript is disabled or is not supported ... visit this page: About CDC.gov . Family Health History The Basics Family Health History & Chronic Disease Planning ...

  8. Family Privilege

    ERIC Educational Resources Information Center

    Seita, John R.

    2014-01-01

    Family privilege is defined as "strengths and supports gained through primary caring relationships." A generation ago, the typical family included two parents and a bevy of kids living under one roof. Now, every variation of blended caregiving qualifies as family. But over the long arc of human history, a real family was a…

  9. transthyretin — EDRN Public Portal

    Cancer.gov

    Transthyretin, one of the three prealbumins including alpha-1-antitrypsin, transthyretin and orosomucoid, is a carrier protein that transports thyroid hormones in the plasma and cerebrospinal fluid, and also transports retinol (vitamin A) in the plasma. TT consists of a tetramer of identical subunits. More than 80 different mutations in this gene have been reported; most mutations are related to amyloid deposition, affecting predominantly peripheral nerve and/or the heart, and a small portion of the gene mutations is non-amyloidogenic. The diseases caused by mutations include amyloidotic polyneuropathy, euthyroid hyperthyroxinaemia, amyloidotic vitreous opacities, cardiomyopathy, oculoleptomeningeal amyloidosis, meningocerebrovascular amyloidosis, and carpal tunnel syndrome.

  10. Meningoencephalitis-like onset of post-infectious AQP4-IgG-positive optic neuritis complicated by GM1-IgG-positive acute polyneuropathy.

    PubMed

    Benedetti, Luana; Franciotta, Diego; Beronio, Alessandro; Delucchi, Stefano; Capellini, Cesare; Del Sette, Massimo

    2015-02-01

    Fifteen days after a respiratory infection, a 45-year-old woman presented with paresthesias in the hands and feet, bilateral loss of vision, fever, headache, and impairment of consciousness. Magnetic resonance imaging (MRI) showed predominant lesions in the optic tracts, optic chiasm, and hypothalamus. Cerebrospinal fluid analysis revealed elevated protein level, and lymphocytic pleocytosis. Neurophysiological studies disclosed a demyelinating sensorimotor polyneuropathy. Serum anti-Mycoplasma pneumoniae immunoglobulin (Ig)M, anti-GM1 IgG, and anti-AQP4 IgG were positive. This case, which is remarkable for post-infectious meningoencephalitis-like onset, MRI picture, and dysimmunity to central and peripheral nervous system autoantigens, underpins the pivotal diagnostic role of anti-AQP4-IgG, and expands the list of clinico-pathological findings that can associate with neuromyelitis optica spectrum disorders. PMID:24557856

  11. A case report: isolated a heavy chain monoclonal gammopathy in a patient with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin change syndrome.

    PubMed

    Kim, S K; Park, I K; Park, B H; Park, W; Lee, H S; Kim, T H; Jun, J B; Bae, S C; Yoo, D H; Uhm, W S

    2005-04-01

    A 45-year-old South-Korean man presented with abdominal distension, progressive paresthesia and motor weakness of both lower extremities. Our case was identified as polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin change (POEMS) syndrome based on diagnostic criteria. Circulating M components of POEMS syndrome consist mainly of IgG or IgA-lambda and rarely IgM-lambda, IgG-kappa or isolated light chains. In this case, the M-band on serum protein electrophoresis and isolated IgA heavy chain on serum immunofixation electrophoresis were demonstrated, but there was no abnormal light chain. We suggest that this case may be associated with a pattern of abnormal secretion of monoclonal protein or a coincidence of a heavy chain disease in POEMS syndrome, even though the latter possibility may be very rare. PMID:15875614

  12. Magnetic Resonance Imaging Evidence of Varicella Zoster Virus Polyneuropathy: Involvement of the Glossopharyngeal and Vagus Nerves Associated With Ramsay Hunt Syndrome.

    PubMed

    Gunbey, Hediye Pinar; Kutlar, Gokhan; Aslan, Kerim; Sayit, Asli Tanrivermis; Incesu, Lutfi

    2016-05-01

    The involvement of lower cranial nerve palsies is less frequent in Ramsay Hunt syndrome caused by varicella zoster virus (VZV). The authors report 1 of extremely rare patients of radiologically proven polyneuropathy of VZV infection with magnetic resonance imaging findings of VII, IX, and X cranial nerve involvement is a 62-year-old female patient, who initially presented with Ramsay Hunt syndrome. Varicella zoster virus infection should be considered even in patients who show unilateral palsy of the lower cranial nerves associated with laryngeal paralysis. Thin-section T2W and T1W images with a contrast agent should be added to the imaging protocol to show the subtle involvement. PMID:27092925

  13. Effect of Ranirestat on Sensory and Motor Nerve Function in Japanese Patients with Diabetic Polyneuropathy: A Randomized Double-Blind Placebo-Controlled Study

    PubMed Central

    Satoh, Jo; Kohara, Nobuo; Sekiguchi, Kenji; Yamaguchi, Yasuyuki

    2016-01-01

    We conducted a 26-week oral-administration study of ranirestat (an aldose reductase inhibitor) at a once-daily dose of 20 mg to evaluate its efficacy and safety in Japanese patients with diabetic polyneuropathy (DPN). The primary endpoint was summed change in sensory nerve conduction velocity (NCV) for the bilateral sural and proximal median sensory nerves. The sensory NCV was significantly (P = 0.006) improved by ranirestat. On clinical symptoms evaluated with the use of modified Toronto Clinical Neuropathy Score (mTCNS), obvious efficacy was not found in total score. However, improvement in the sensory test domain of the mTCNS was significant (P = 0.037) in a subgroup of patients diagnosed with neuropathy according to the TCNS severity classification. No clinically significant effects on safety parameters including hepatic and renal functions were observed. Our results indicate that ranirestat is effective on DPN (Japic CTI-121994). PMID:26881251

  14. Cancer, Families, and Family Counselors.

    ERIC Educational Resources Information Center

    Duffy, Maureen; Gillig, Scott

    2003-01-01

    Examines the role of the family counselor in working with cancer patients and their families. Suggests ways in which the family counselor can work proactively with families in the area of cancer prevention and helping them cope more effectively with its impact on their lives. Uses a clinical case example to illustrate intervention with cancer…

  15. Family therapy by family doctors

    PubMed Central

    Neighbour, R.

    1982-01-01

    The experiences of a group of general practitioners learning and attempting family therapy are described. Three principles for working with whole families — facilitation, formulation and focussing — are illustrated by case histories. Family therapy in general practice can be effective for patients and worthwhile for family doctors. PMID:7153974

  16. A mutation in the Warburg syndrome gene, RAB3GAP1, causes a similar syndrome with polyneuropathy and neuronal vacuolation in Black Russian Terrier dogs.

    PubMed

    Mhlanga-Mutangadura, Tendai; Johnson, Gary S; Schnabel, Robert D; Taylor, Jeremy F; Johnson, Gayle C; Katz, Martin L; Shelton, G Diane; Lever, Teresa E; Giuliano, Elizabeth; Granger, Nicolas; Shomper, Jeremy; O'Brien, Dennis P

    2016-02-01

    An autosomal recessive disease of Black Russian Terriers was previously described as a juvenile-onset, laryngeal paralysis and polyneuropathy similar to Charcot Marie Tooth disease in humans. We found that in addition to an axonal neuropathy, affected dogs exhibit microphthalmia, cataracts, and miotic pupils. On histopathology, affected dogs exhibit a spongiform encephalopathy characterized by accumulations of abnormal, membrane-bound vacuoles of various sizes in neuronal cell bodies, axons and adrenal cells. DNA from an individual dog with this polyneuropathy with ocular abnormalities and neuronal vacuolation (POANV) was used to generate a whole genome sequence which contained a homozygous RAB3GAP1:c.743delC mutation that was absent from 73 control canine whole genome sequences. An additional 12 Black Russian Terriers with POANV were RAB3GAP1:c.743delC homozygotes. DNA samples from 249 Black Russian Terriers with no known signs of POANV were either heterozygotes or homozygous for the reference allele. Mutations in human RAB3GAP1 cause Warburg micro syndrome (WARBM), a severe developmental disorder characterized by abnormalities of the eye, genitals and nervous system including a predominantly axonal peripheral neuropathy. RAB3GAP1 encodes the catalytic subunit of a GTPase activator protein and guanine exchange factor for Rab3 and Rab18 respectively. Rab proteins are involved in membrane trafficking in the endoplasmic reticulum, axonal transport, autophagy and synaptic transmission. The neuronal vacuolation and membranous inclusions and vacuoles in axons seen in this canine disorder likely reflect alterations of these processes. Thus, this canine disease could serve as a model for WARBM and provide insight into its pathogenesis and treatment. PMID:26607784

  17. Chronic inflammatory polyneuropathy

    MedlinePlus

    ... Tests may include: Electromyography ( EMG ) Nerve conduction tests Nerve biopsy Spinal tap Blood tests may be done to look for specific proteins that are causing the immune attack on the nerves Which other tests are done depends on the ...

  18. FAMILIAL SUICIDE

    PubMed Central

    Unni, K.E. Sadanaandan

    1996-01-01

    Seven completed suicides in a family of lower socioeconomic status and suburban domicile in Pondicherry are reported. The presence of bipolar affective disorder in the family members and the absence of exogenous factors are illustrated by utilising both family history method and family study method. The details collected formed the basis for the terminology ‘familial suicide’. The management of the index case, one of the only three surviving male members of the family, who presented with suicidal ruminations and depressive features, is described. PMID:21584122

  19. Family Matters.

    ERIC Educational Resources Information Center

    Mainor, Peggy

    2001-01-01

    Describes a Kellogg Family Collaborative project that involves the University of Montana and four tribal colleges in a family-strengths approach to improving student retention and achievement. States that the project is grounded in social work theory and research that recognize and reinforce family and student resilience through promotion of…

  20. Family Support.

    ERIC Educational Resources Information Center

    Wieck, Colleen, Ed.; McBride, Marijo, Ed.

    1990-01-01

    This "Feature Issue" of the quarterly journal "Impact" presents 19 brief articles on family support systems in the United States for persons with developmental disabilities and their families. Emphasis is on provisions of Public Law 99-457. Articles include: "Family Support in the United States: Setting a Course for the 1990s" (James Knoll);…

  1. Rural Families.

    ERIC Educational Resources Information Center

    Goetz, Kathy, Ed.

    1992-01-01

    This "special focus" journal issue consists of 13 individual articles on the theme of rural family programs relating to school, health services, church, and other institutions. It includes: (1) "Towards a Rural Family Policy" (Judith K. Chynoweth and Michael D. Campbell); (2) "Montana: Council for Families Collaborates for Prevention (Jean…

  2. The flavonoid luteolin, but not luteolin-7-O-glucoside, prevents a transthyretin mediated toxic response.

    PubMed

    Iakovleva, Irina; Begum, Afshan; Pokrzywa, Malgorzata; Walfridsson, Malin; Sauer-Eriksson, A Elisabeth; Olofsson, Anders

    2015-01-01

    Transthyretin (TTR) is a homotetrameric plasma protein with amyloidogenic properties that has been linked to the development of familial amyloidotic polyneuropathy (FAP), familial amyloidotic cardiomyopathy, and senile systemic amyloidosis. The in vivo role of TTR is associated with transport of thyroxine hormone T4 and retinol-binding protein. Loss of the tetrameric integrity of TTR is a rate-limiting step in the process of TTR amyloid formation, and ligands with the ability to bind within the thyroxin binding site (TBS) can stabilize the tetramer, a feature that is currently used as a therapeutic approach for FAP. Several different flavonoids have recently been identified that impair amyloid formation. The flavonoid luteolin shows therapeutic potential with low incidence of unwanted side effects. In this work, we show that luteolin effectively attenuates the cytotoxic response to TTR in cultured neuronal cells and rescues the phenotype of a Drosophila melanogaster model of FAP. The plant-derived luteolin analogue cynaroside has a glucoside group in position 7 of the flavone A-ring and as opposed to luteolin is unable to stabilize TTR tetramers and thus prevents a cytotoxic effect. We generated high-resolution crystal-structures of both TTR wild type and the amyloidogenic mutant V30M in complex with luteolin. The results show that the A-ring of luteolin, in contrast to what was previously suggested, is buried within the TBS, consequently explaining the lack of activity from cynaroside. The flavonoids represent an interesting group of drug candidates for TTR amyloidosis. The present investigation shows the potential of luteolin as a stabilizer of TTR in vivo. We also show an alternative orientation of luteolin within the TBS which could represent a general mode of binding of flavonoids to TTR and is of importance concerning the future design of tetramer stabilizing drugs. PMID:26020516

  3. The Flavonoid Luteolin, but Not Luteolin-7-O-Glucoside, Prevents a Transthyretin Mediated Toxic Response

    PubMed Central

    Pokrzywa, Malgorzata; Walfridsson, Malin; Sauer-Eriksson, A. Elisabeth; Olofsson, Anders

    2015-01-01

    Transthyretin (TTR) is a homotetrameric plasma protein with amyloidogenic properties that has been linked to the development of familial amyloidotic polyneuropathy (FAP), familial amyloidotic cardiomyopathy, and senile systemic amyloidosis. The in vivo role of TTR is associated with transport of thyroxine hormone T4 and retinol-binding protein. Loss of the tetrameric integrity of TTR is a rate-limiting step in the process of TTR amyloid formation, and ligands with the ability to bind within the thyroxin binding site (TBS) can stabilize the tetramer, a feature that is currently used as a therapeutic approach for FAP. Several different flavonoids have recently been identified that impair amyloid formation. The flavonoid luteolin shows therapeutic potential with low incidence of unwanted side effects. In this work, we show that luteolin effectively attenuates the cytotoxic response to TTR in cultured neuronal cells and rescues the phenotype of a Drosophila melanogaster model of FAP. The plant-derived luteolin analogue cynaroside has a glucoside group in position 7 of the flavone A-ring and as opposed to luteolin is unable to stabilize TTR tetramers and thus prevents a cytotoxic effect. We generated high-resolution crystal-structures of both TTR wild type and the amyloidogenic mutant V30M in complex with luteolin. The results show that the A-ring of luteolin, in contrast to what was previously suggested, is buried within the TBS, consequently explaining the lack of activity from cynaroside. The flavonoids represent an interesting group of drug candidates for TTR amyloidosis. The present investigation shows the potential of luteolin as a stabilizer of TTR in vivo. We also show an alternative orientation of luteolin within the TBS which could represent a general mode of binding of flavonoids to TTR and is of importance concerning the future design of tetramer stabilizing drugs. PMID:26020516

  4. Coexistent Charcot-Marie-Tooth type 1A and type 2 diabetes mellitus neuropathies in a Chinese family

    PubMed Central

    Sun, A-ping; Tang, Lu; Liao, Qin; Zhang, Hui; Zhang, Ying-shuang; Zhang, Jun

    2015-01-01

    Charcot-Marie-Tooth disease type 1A (CMT1A) is caused by duplication of the peripheral myelin protein 22 (PMP22) gene on chromosome 17. It is the most common inherited demyelinating neuropathy. Type 2 diabetes mellitus is a common metabolic disorder that frequently causes predominantly sensory neuropathy. In this study, we report the occurrence of CMT1A in a Chinese family affected by type 2 diabetes mellitus. In this family, seven individuals had duplication of the PMP22 gene, although only four had clinical features of polyneuropathy. All CMT1A patients with a clinical phenotype also presented with type 2 diabetes mellitus. The other three individuals had no signs of CMT1A or type 2 diabetes mellitus. We believe that there may be a genetic link between these two diseases. PMID:26692872

  5. Coexistent Charcot-Marie-Tooth type 1A and type 2 diabetes mellitus neuropathies in a Chinese family.

    PubMed

    Sun, A-Ping; Tang, Lu; Liao, Qin; Zhang, Hui; Zhang, Ying-Shuang; Zhang, Jun

    2015-10-01

    Charcot-Marie-Tooth disease type 1A (CMT1A) is caused by duplication of the peripheral myelin protein 22 (PMP22) gene on chromosome 17. It is the most common inherited demyelinating neuropathy. Type 2 diabetes mellitus is a common metabolic disorder that frequently causes predominantly sensory neuropathy. In this study, we report the occurrence of CMT1A in a Chinese family affected by type 2 diabetes mellitus. In this family, seven individuals had duplication of the PMP22 gene, although only four had clinical features of polyneuropathy. All CMT1A patients with a clinical phenotype also presented with type 2 diabetes mellitus. The other three individuals had no signs of CMT1A or type 2 diabetes mellitus. We believe that there may be a genetic link between these two diseases. PMID:26692872

  6. Fanconi anemia with biallelic FANCD1/BRCA2 mutations - Case report of a family with three affected children.

    PubMed

    Svojgr, Karel; Sumerauer, David; Puchmajerova, Alena; Vicha, Ales; Hrusak, Ondrej; Michalova, Kyra; Malis, Josef; Smisek, Petr; Kyncl, Martin; Novotna, Drahuse; Machackova, Eva; Jencik, Jan; Pycha, Karel; Vaculik, Miroslav; Kodet, Roman; Stary, Jan

    2016-03-01

    Fanconi anemia, complementation group D1 with bi-allelic FANCD1 (BRCA2) mutations, is a very rare genetic disorder characterized by early onset of childhood malignancies, including acute leukemia, brain cancer and nephroblastoma. Here, we present a case report of a family with 3 affected children in terms of treatment outcome, toxicity and characterization of the malignancies using comprehensive cytogenetic analysis. The first child was diagnosed with T-cell acute lymphoblastic leukemia when he was 11 months old. During chemotherapy, he suffered from repeated pancytopenia, sepsis and severe vincristine polyneuropathy, and 18 months after primary diagnosis, he succumbed to secondary acute monocytic leukemia. The second child was diagnosed with stage 2 triphasic nephroblastoma (Wilms tumor), when he was 3 years and 11 months old. During chemotherapy, he suffered from vincristine polyneuropathy. Currently, he is in complete remission, 29 months following the initial diagnosis. The third child was diagnosed with medulloblastoma with classical histology, when she was 4 years and 5 months old. After the first cycle of chemotherapy, she suffered from prolonged pancytopenia, sepsis and severe skin and mucosal toxicity. Six weeks after primary diagnosis, a first relapse in the posterior fossa was diagnosed, and at 7 and half months after primary diagnosis, a second relapse was diagnosed that led to the patient's death. Our case report underscores tumor heterogeneity, treatment toxicity and poor outcome in Fanconi anemia patients of complementation group D1. PMID:26657402

  7. FAMILY LYGISTORRHINIDAE.

    PubMed

    Oliveira, Sarah Siqueira; Amorim, Dalton De Souza

    2016-01-01

    The Lygistorrhinidae are a family belonging to the suborder Bibionomorpha, with no previous record from Colombia. This paper refers for the first time to the occurrence of the family in the country, an undetermined species of the genus Lygistorrhina (Probolaeus) Williston. PMID:27395260

  8. Family Potyviridae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The International Committee on the Taxonomy of Viruses potyvirus study group has revised the description of the family Potyviridae for inclusion in the ICTV 9th report. Characteristic features of each genus within the family is presented. Revised criteria for demarcation and nomenclature of viral sp...

  9. Family Empowerment.

    ERIC Educational Resources Information Center

    Sinclair, Mary F., Ed.; And Others

    1992-01-01

    This feature issue of IMPACT focuses on the empowerment of families with a member who has a developmental disability. It presents strategies and models for a collaborative, respectful approach to service provision, and presents the experiences of families in seeking support and assistance. Feature articles include "Two Generations of Disability: A…

  10. Family Workshops

    ERIC Educational Resources Information Center

    Bennett, Dave; Rees-Jones, Tanny

    1978-01-01

    A Family Workshop is an informal, multidisciplined educational program for adults and children, organized by a team of teachers. This article discusses the Lavender Hill Family Workshop, one of many, which attempts to provide education in various subject areas for adults and for children while also integrating both objectives in order to educate…

  11. Family Life.

    ERIC Educational Resources Information Center

    Naturescope, 1986

    1986-01-01

    Focuses on various aspects of mammal family life ranging from ways different species are born to how different mammals are raised. Learning activities include making butter from cream, creating birth announcements for mammals, and playing a password game on family life. (ML)

  12. Changes of Thyroid Hormones and Their Binding Proteins during Plasma Exchange for Polyneuropathy in a Patient with Substituted Hypothyroidism due to Hashimoto's Thyroiditis

    PubMed Central

    Jenni, Stefan; Adler, Marcel; Lanz, Simone; Taleghani, Behrouz Mansouri; Christ, Emanuel R.

    2016-01-01

    Summary Background Pharmacodynamic studies and data concerning adaptation of thyroid substitution in patients with substituted hypothyroidism during plasma exchange (PE) is not available. Case Report We measured TSH, fT3 and fT4, total T4, thyroxin binding globulin (TBG), and albumin before and after 5 PE procedures in a 37-year-old women who underwent PE for a therapy-resistant polyneuropathy. Thyroxin was increased empirically by 8% resulting in a dose of 1.95 µg/kg per day. Results: Despite larger reductions of total T4 and TBG over a series of 5 PEs (40-50% from baseline), only small reductions of 8% in fT3 and fT4 concentrations were documented with a concomittant increase in TSH level. Changes of fT4, fT3, and TSH remained within normal range. Conclusions: i) Despite a significant decrease in total thyroid hormone pool following PE, fT4, fT3, and TSH concentrations changed only slightly. ii) Based on this observation, a general increase in thyroid replacement therapy before PE cannot be recommended, but considered in case of a high normal TSH level. PMID:27022322

  13. A RAB3GAP1 SINE Insertion in Alaskan Huskies with Polyneuropathy, Ocular Abnormalities, and Neuronal Vacuolation (POANV) Resembling Human Warburg Micro Syndrome 1 (WARBM1)

    PubMed Central

    Wiedmer, Michaela; Oevermann, Anna; Borer-Germann, Stephanie E.; Gorgas, Daniela; Shelton, G. Diane; Drögemüller, Michaela; Jagannathan, Vidhya; Henke, Diana; Leeb, Tosso

    2015-01-01

    We observed a hereditary phenotype in Alaskan Huskies that was characterized by polyneuropathy with ocular abnormalities and neuronal vacuolation (POANV). The affected dogs developed a progressive severe ataxia, which led to euthanasia between 8 and 16 months of age. The pedigrees were consistent with a monogenic autosomal recessive inheritance. We localized the causative genetic defect to a 4 Mb interval on chromosome 19 by a combined linkage and homozygosity mapping approach. Whole genome sequencing of one affected dog, an obligate carrier, and an unrelated control revealed a 218-bp SINE insertion into exon 7 of the RAB3GAP1 gene. The SINE insertion was perfectly associated with the disease phenotype in a cohort of 43 Alaskan Huskies, and it was absent from 541 control dogs of diverse other breeds. The SINE insertion induced aberrant splicing and led to a transcript with a greatly altered exon 7. RAB3GAP1 loss-of-function variants in humans cause Warburg Micro Syndrome 1 (WARBM1), which is characterized by additional developmental defects compared to canine POANV, whereas Rab3gap1-deficient mice have a much milder phenotype than either humans or dogs. Thus, the RAB3GAP1 mutant Alaskan Huskies provide an interesting intermediate phenotype that may help to better understand the function of RAB3GAP1 in development. Furthermore, the identification of the presumed causative genetic variant will enable genetic testing to avoid the nonintentional breeding of affected dogs. PMID:26596647

  14. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, multiple myeloma and skin changes) with cranial vault plasmocytoma and the role of surgery in its management: a case report

    PubMed Central

    2013-01-01

    Introduction POEMS syndrome (an acronym of polyneuropathy, organomegaly, endocrinopathy, multiple myeloma and skin changes) is a paraneoplastic disorder related to an underlying plasma cell dyscrasia. The development of such a syndrome is rare and its association with calvarial plasmocytoma is even less common, with only two previous reported cases. We describe, in detail, an unusual presentation of cranial plasmocytoma associated with POEMS syndrome and briefly discuss the possible role of surgery in the management of this disease. Case presentation We present the case of a 45-year-old Caucasian man who was admitted to our department presenting with progressive weakness in his lower limbs, enlarged lymph nodes and a large mass on the scalp with intense bone erosion. POEMS criteria were present and pathological studies confirmed a Castleman’s variant plasmocytoma. Clinical status improved noticeably after the excision of the plasmocytoma and the treatment was completed with radiotherapy and steroid pulse therapy. Conclusion Cranial vault plasmocytoma and its association with POEMS syndrome are rare conditions with few previously reported cases. Although the role of surgery is not clearly defined in POEMS syndrome guidelines, the fact that there seems to be a better prognosis and clinical outcome when surgery is used as a part of the management in POEMS syndrome with cranial vault plasmocytoma is worth discussing. PMID:24139142

  15. Cost-utility of Intravenous Immunoglobulin (IVIG) compared with corticosteroids for the treatment of Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) in Canada

    PubMed Central

    2010-01-01

    Objectives Intravenous immunoglobulin (IVIG) has demonstrated improvement in chronic inflammatory demyelinating polyneuropathy (CIDP) patients in placebo controlled trials. However, IVIG is also much more expensive than alternative treatments such as corticosteroids. The objective of the paper is to evaluate, from a Canadian perspective, the cost-effectiveness of IVIG compared to corticosteroid treatment of CIDP. Methods A markov model was used to evaluate the costs and QALYs for IVIG and corticosteroids over 5 years of treatment for CIDP. Patients initially responding to IVIG could remain a responder or relapse every 12 week model cycle. Non-responding IVIG patients were assumed to be switched to corticosteroids. Patients on corticosteroids were at risk of a number of adverse events (fracture, diabetes, glaucoma, cataract, serious infection) in each cycle. Results Over the 5 year time horizon, the model estimated the incremental costs and QALYs of IVIG treatment compared to corticosteroid treatment to be $124,065 and 0.177 respectively. The incremental cost per QALY gained of IVIG was estimated to be $687,287. The cost per QALY of IVIG was sensitive to the assumptions regarding frequency and dosing of maintenance IVIG. Conclusions Based on common willingness to pay thresholds, IVIG would not be perceived as a cost effective treatment for CIDP. PMID:20565778

  16. [Utility of electrophysiologic study using the blink reflex and brainstem evoked potentials for the evaluation of the course of uremic polyneuropathy].

    PubMed

    Baldini, S; Radicioni, R; Melappioni, M; Baldassari, M; Panichi, N; Pelliccioni, G; Guidi, M; Rosa, L; Magnaterra, R; Scarpino, O

    1995-03-01

    On the present study the authors evaluate the utility of electrophysiologic examination in uraemic polyneuropathy. A group of 19 uraemic patients in chronic dialysis underwent the Blink reflex and BAEPSs study to evaluate the alterations of nervous pathways. The results obtained were compared with those of a group of 10 healthy patients comparable for age and sex. The electrophysiologic parameters have been statistically compared with the plasma levels of vit. B12. folic acid, PTH and beta-2-microglobulin. The results show a significant difference of uremic patients compared with the healthy ones for the Blink reflex (ipsilateral and contralateral R2 responses). Also BAEPSs show significant alterations in the uraemic group (latencies of the III, V components). A statistically significantly inverse correlation is present between folic acid values and blink reflex R1 and R2 responses. Therefore our study shows the existence of a combined degeneration of central and peripheral nervous pathways in chronic uraemic patients. We believe that the decrease in folic acid concentration found in our study may be one of the causes of the beginning and then of the worsening of neurologic damage. PMID:7570255

  17. [Transthyretin-related amyloidotic cardiomyopathy: looking for the etiological treatment].

    PubMed

    Longhi, Simone; Gagliardi, Christian; Milandri, Agnese; Manuzzi, Lisa; Rapezzi, Claudio

    2014-05-01

    Transthyretin (TTR)-related amyloidosis is a disease caused by the deposition of insoluble fibrils deriving from the misfolding of TTR, a protein mainly produced by the liver. In the hereditary form of the disease (ATTRm), protein misfolding is secondary to a mutation in the TTR gene. ATTRm can manifest with different phenotypes: mainly neurological, mainly cardiac, or mixed. In the senile form of the disease (wild-type TTR or SSA), the deposition of non-mutated TTR occurs and, clinically, cardiomyopathy is predominant. Cardiac amyloidosis is still an underdiagnosed disease and clinical heterogeneity makes the diagnosis challenging. Until recently, no specific pharmacological treatment was available, liver transplantation being the only therapeutic option aimed at slowing disease progression in ATTRm and treatment was based on symptom relief. This review focuses on the emerging pharmacological treatments for TTR-related amyloidosis targeting different steps of the amyloidogenic process (blocking hepatic TTR synthesis, TTR tetramer stabilization and promotion of TTR amyloid fibril clearance). PMID:25002169

  18. Family Health and Family Planning.

    ERIC Educational Resources Information Center

    World Health Organization, Copenhagen (Denmark). Regional Office for Europe.

    This document is made up of a selection of some of the papers distributed to participants in courses on "Family Health and Family Planning" which have been organized each year since 1973 by the International Children's Center and the World Health Organization Regional Office for Europe. Six courses, held between 1973 and 1978, brought together a…

  19. FAMILY BIBIONIDAE.

    PubMed

    Falaschi, Rafaela Lopes; Oliveira, Sarah Siqueira; Amorim, Dalton De Souza

    2016-01-01

    The Bibionidae are a family belonging to the suborder Bibionomorpha with four genera and 17 species known from Colombia. This work expands the distribution of these species to other localities in the country. PMID:27395253

  20. Tomorrow's Family

    ERIC Educational Resources Information Center

    Pickett, Robert S.

    1977-01-01

    Author states that "...the traditional form of family which has been the norm in recent times in the West will persist, but will be forced to "move over" to accommodate other forms of domestic life." (Author)

  1. Unusual families.

    PubMed

    Golombok, Susan

    2005-03-01

    The introduction of assisted reproduction has led to unusual forms of procreation. This article describes the social consequences of lesbian motherhood and of families headed by single heterosexual mothers. PMID:15819999

  2. FAMILY RHAGIONIDAE.

    PubMed

    Santos, Charles Morphy D; Carmo, Daniel D D

    2016-01-01

    The family Rhagionidae is one of the oldest Brachyeran lineages. Its monophyly is still uncertain. There are four rhagionid genera distributed in Neotropical Region but only three species of Chrysopilus are found in Colombia. PMID:27395270

  3. Family Issues

    MedlinePlus

    ... not mean that everyone gets along all the time. Conflicts are a part of family life. Many things can lead to conflict, such as illness, disability, addiction, job loss, school problems, and marital issues. Listening to ...

  4. Family Limitation

    PubMed Central

    Smith, Robert

    1966-01-01

    Dr Robert Smith surveys the history of birth control and sounds a warning for the future of mankind, if the population explosion is allowed to continue unchecked. He stresses the importance of the role of the general practitioner in the limitation of births. Sir Theodore Fox describes the work of the Family Planning Association and stresses that, increasingly, this is a specialist service covering all aspects of fertility. He also feels that the general practitioner has a role in family planning. PMID:5954261

  5. Family welfare.

    PubMed

    Sinha, N K

    1992-01-01

    Between 1901-1921, India gained 12.9 million people because mortality remained high. The death rate fell between 1921-1951, but birth rates remained the same. Therefore 110 million people were added--2 times the population increase between 1891-1921. Between 1951-1981, the population increased to 324 million. Socioeconomic development was responsible for most of the downward trend in the birth rate during the 20th century. Even though large families were the norm in early India, religious leaders encouraged small family size. The 1st government family planning clinics in the world opened in Mysore and Bangalore in 1930. Right before Independence, the Bhore Committee made recommendations to reduce population growth such as increasing the age of marriage for girls. Since 1951 there has been a change in measures and policies geared towards population growth with each of the 7 5-Year Plans because policy makers applied what they learned from each previous plan. The 1st 5-Year Plan emphasized the need to understand what factors contribute to population growth. It also integrated family planning services into health services of hospitals and health centers. The government was over zealous in its implementation of the sterilization program (2nd 5-Year Plan, 1956-1961), however, which hurt family planning programs for many years. As of early 1992, sterilization, especially tubectomy, remained the most popular family planning method, however. The 7th 5-Year Plan changed its target of reaching a Net Reproductive Rate of 1 by 2001 to 2006-2011. It set a goal of 100% immunization coverage by 1990 but it did not occur. In 1986, the Ministry of Health and Family Welfare planned to make free contraceptives available in urban and rural areas and to involve voluntary organizations. The government needs to instill measures to increase women's status, women's literacy, and age of marriage as well as to eliminate poverty, ensure old age security, and ensure child survival and

  6. FAMILY STRATIOMYIDAE.

    PubMed

    Fachin, Diego Aguilar; De Assis-Pujol, Cristiane Vieira

    2016-01-01

    The family Stratiomyidae has more than 2,800 described species, of which 1001 species belongs to the Neotropics. This catalog for Colombia presents 87 species distributed in 32 genera, and ten subfamilies. Merosargus gracilis and the genus Microchrysa, with a single species M. bicolor are recorded for the first time to Colombia. The fauna is very expressive but still poorly known, representing nearly one tenth of the Neotropical diversity of the family in numbers of species, and one fifth of generic diversity. PMID:27395274

  7. Familial Hypercholesterolemia.

    PubMed

    Bouhairie, Victoria Enchia; Goldberg, Anne Carol

    2016-03-01

    Familial hypercholesterolemia is a common, inherited disorder of cholesterol metabolism that leads to early cardiovascular morbidity and mortality. It is underdiagnosed and undertreated. Statins, ezetimibe, bile acid sequestrants, niacin, lomitapide, mipomersen, and low-density lipoprotein (LDL) apheresis are treatments that can lower LDL cholesterol levels. Early treatment can lead to substantial reduction of cardiovascular events and death in patients with familial hypercholesterolemia. It is important to increase awareness of this disorder in physicians and patients to reduce the burden of this disorder. PMID:26892994

  8. Family-Centered Child Care. Families Matter.

    ERIC Educational Resources Information Center

    Lopez, M. Elena; Dorros, Sybilla

    The Families Matter series of papers from the Harvard Family Research Project advances the concept of family-centered child care, advocating an approach to early childhood education that addresses the development of the child and family together. Grounded in family support principles, which build on family strengths and work from a community's…

  9. Income and Family Events: Family Income, Family Size, and Consumption

    ERIC Educational Resources Information Center

    Cutright, Phillips

    1971-01-01

    This paper considers the structure of family income, examines some factors affecting family size, reviews alternative definitions of an adequate income for families with varying numbers, and presents data on actual consumption, according to family income and family size. A model depicting the causal relations among factors affecting consumption is…

  10. FAMILY ASILIDAE.

    PubMed

    Wolff, Marta; Lamas, Carlos José Einicker

    2016-01-01

    Asilidae is one of the largest Diptera families with more than 7,000 recognized species worldwide. All their species are predators on arthropods, mainly insects. This catalogue presents 71 species distributed in 26 genera, ten tribes or generic groups and four subfamilies. For each species we present the available geographical information and relevant references. PMID:27395278