Barbosa, Margarida; Saavedra, Ana; Severo, Milton; Maier, Christoph; Carvalho, Davide
Diabetic peripheral neuropathy is very common in the diabetic population. Early screening for foot pathology is of the utmost importance. The Michigan Neuropathy Screening Instrument (MNSI) is an easy, brief, and noninvasive screening tool. The aim of this study was to validate the semantics and characteristics of both sections of the Portuguese translation of the MNSI for Portuguese diabetic patients. A cross-sectional study was performed on 87 type 1 and 2 diabetic patients at our outpatient endocrinology department. The final sample was composed of 76 patients. Nerve conduction studies were requested, but only a subsample of 42 patients agreed to participate in them. The scale was internally consistent (Cronbach's alpha > 0.70 in section A, or a clinical history questionnaire and a physical examination [section B]), and the scores of both sections were positively correlated (r = 0.70; P Portuguese MNSI is a reliable and valid tool for screening diabetic neuropathy. © 2016 World Institute of Pain.
Full Text Available Background and Aims: Little data regarding distal symmetric polyneuropathy (DSP prevalence in Romania is available. The aim of the present study was to assess the prevalence of DSP in our cohort, to characterize it depending on glycemic control, and also to find an easy-to-apply method for DSP screening which could be used in Romania.
Muntean Cristina; Cătălin Bogdan; Tudorică Valerica; Moţa Maria
Background and Aims: Little data regarding distal symmetric polyneuropathy (DSP) prevalence in Romania is available. The aim of the present study was to assess the prevalence of DSP in our cohort, to characterize it depending on glycemic control, and also to find an easy-to-apply method for DSP screening which could be used in Romania.
Pulse pressure and michigan neuropathy screening instrument are independently associated with asymptomatic peripheral arterial disease among type 2 diabetes community residents: A community-based screening program in Taiwan
Full Text Available Background: Peripheral arterial disease (PAD is one of the major manifestations of systemic atherosclerosis and plays an important role in low-extremity amputation in type 2 diabetic patients. The aim of this study was to explore the prevalence and risk factors for asymptomatic PAD in type 2 diabetic community residents. Methods: This cross-sectional study enrolled 552 type 2 diabetic adults (232 men and 320 women without subjective symptoms of intermittent claudication. We defined the PAD group as an ankle-brachial index (ABI ≤ 0.90, and the normal group as an ABI 0.91-1.30. Their clinical characteristics, Michigan Neuropathy Screening Instrument (MNSI scores and blood pressure were compared. Results: We discovered that 51 patients have asymptomatic PAD. Univariate logistic regression analysis revealed that age, history of stroke, longer duration of diabetes (> 10 years, unemployment or retirement, pulse pressure, systolic blood pressure, and high MNSI score (> 2 were risk factors for PAD. By multivariate logistic regression analysis, pulse pressure, high MNSI score, age, and history of stroke were independent risk factors with odds ratios (95% confidence intervals, CI of 1.032 (1.012-1.053, 2.359 (1.274-4.370, 1.050 (1.010-1.091, and 5.152 (1.985-13.368, respectively. Furthermore, the prevalence of PAD increased significantly with increment in the pulse pressure and MNSI. Conclusions: In summary, the overall prevalence of asymptomatic PAD in the type 2 diabetic adults was 9.2%. Age, history of stroke, pulse pressure and MNSI score may provide important clinical information. Primary care physicians should be aware of asymptomatic patients with high pulse pressure and MNSI scores.
Storgaard, H; Nielsen, S D; Gluud, C
This review examines the validity of the Michigan Alcoholism Screening Test (MAST) as a screening instrument for alcohol problems. Studies that compare the MAST-questionnaire with other defined diagnostic criteria of alcohol problems were retrieved through MEDLINE and a cross-bibliographic check...
Snow, Mark; Thurber, Steven; Hodgson, Joele M.
Item content of the Michigan Alcoholism Screening Test (MAST) was modified to make it more appropriate for young persons. The resulting test was found to have lower internal consistency than the adult MAST, but the elimination of five items with comparatively poor psychometric properties yielded an acceptable alpha coefficient. (Contains 10…
Full Text Available Background The involvement of the peripheral nervous system in children with celiac disease is particularly rare. Objective The aim of this study was to assess the need for neurophysiological testing in celiac disease patients without neurological symptoms in order to detect early subclinical neuropathy and its possible correlations with clinical and demographic characteristics. Methods Two hundred and twenty consecutive children with celiac disease were screened for neurological symptoms and signs, and those without symptoms or signs were included. Also, patients with comorbidities associated with peripheral neuropathy or a history of neurological disease were excluded. The remaining 167 asymptomatic patients as well as 100 control cases were tested electro-physiologically for peripheral nervous system diseases. Motor nerve conduction studies, including F-waves, were performed for the median, ulnar, peroneal, and tibial nerves, and sensory nerve conduction studies were performed for the median, ulnar, and sural nerves with H reflex of the soleus muscle unilaterally. All studies were carried out using surface recording electrodes. Normative values established in our laboratory were used. Results Evidence for subclinical neuropathy was not determined with electrophysiological studies in any of the participants. Conclusion In this highly selective celiac disease group without any signs, symptoms as well as the predisposing factors for polyneuropathy, we did not determine any cases with neuropathy. With these results we can conclude that in asymptomatic cases with celiac disease electrophysiological studies are not necessary. However, larger studies with the electrophysiological studies performed at different stages of disease at follow-ups are warranted.
Selvarajah, D; Cash, T; Davies, J; A. Sankar; Rao, G.; Grieg, M.; S. PALLAI; Gandhi, R.; Wilkinson, I. D; Tesfaye, S.
Clinical methods of detecting diabetic peripheral neuropathy (DPN) are not objective and reproducible. We therefore evaluated if SUDOSCAN, a new method developed to provide a quick, non-invasive and quantitative assessment of sudomotor function can reliably screen for DPN. 70 subjects (45 with type 1 diabetes and 25 healthy volunteers [HV]) underwent detailed assessments including clinical, neurophysiological and 5 standard cardiovascular reflex tests (CARTs). Using the American Academy of Ne...
Full Text Available BACKGROUND/AIM: Neuropathy is the most common neurologic complication of HIV but is widely under-diagnosed in resource-constrained settings. We aimed to identify tools that accurately distinguish individuals with moderate/severe peripheral neuropathy and can be administered by non-physician healthcare workers (HCW in resource-constrained settings. METHODS: We enrolled a convenience sample of 30 HIV-infected outpatients from a Kenyan HIV-care clinic. A HCW administered the Neuropathy Severity Score (NSS, Single Question Neuropathy Screen (Single-QNS, Subjective Peripheral Neuropathy Screen (Subjective-PNS, and Brief Peripheral Neuropathy Screen (Brief-PNS. Monofilament, graduated tuning fork, and two-point discrimination examinations were performed. Tools were validated against a neurologist's clinical assessment of moderate/severe neuropathy. RESULTS: The sample was 57% male, mean age 38.6 years, and mean CD4 count 324 cells/µL. Neurologist's assessment identified 20% (6/30 with moderate/severe neuropathy. Diagnostic utilities for moderate/severe neuropathy were: Single-QNS--83% sensitivity, 71% specificity; Subjective-PNS-total--83% sensitivity, 83% specificity; Subjective-PNS-max and NSS--67% sensitivity, 92% specificity; Brief-PNS--0% sensitivity, 92% specificity; monofilament--100% sensitivity, 88% specificity; graduated tuning fork--83% sensitivity, 88% specificity; two-point discrimination--75% sensitivity, 58% specificity. CONCLUSIONS: Pilot testing suggests Single-QNS, Subjective-PNS, and monofilament examination accurately identify HIV-infected patients with moderate/severe neuropathy and may be useful diagnostic tools in resource-constrained settings.
Ferré, Marc; Bonneau, Dominique; Milea, Dan
We report the results of molecular screening in 980 patients carried out as part of their work-up for suspected hereditary optic neuropathies. All the patients were investigated for Leber's hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA), by searching for the ten...... novel OPA1 mutations reported here. The statistical analysis of this large set of mutations has led us to propose a diagnostic strategy that should help with the molecular work-up of optic neuropathies. Our results highlight the importance of investigating LHON-causing mtDNA mutations as well as OPA1...... and OPA3 mutations in cases of suspected hereditary optic neuropathy, even in absence of a family history of the disease....
Full Text Available "n Background and the purpose of the study: Diabetic neuropathy is the most common diabetic complication that often is accompanied by significant morbidity, mortality and economic burden. The purpose of this study was evaluation of effect of Semelil (ANGIPARSTM, a new herbal drug for treatment of diabetic foot ulcers or diabetic peripheral neuropathy. "nMethods: In this double blind clinical trial, 49 type 2 diabetes patients with different degrees of neuropathy were evaluated in two groups (ANGIPARSTM and placebo groups. All patients were assessed at the start and 12 weeks after treatment, with laboratory tests, United Kingdom screening test, Michigan neuropathy screening score, Michigan diabetic neuropathy score, vibration perception thresholds, nerve conduction study, monofilament test and visual analog scale. "nResults: Michigan diabetic neuropathy score was decreased notably in ANGIPARSTM group. In the nerve conduction study, appropriate meaningful changes were observed in the distal latency and amplitude in the motor Ulnar nerve in ANGIPARSTM group. Conclusion: The results showed limited evidence of efficacy of ANGIPARSTM in diabetic neuropathy treatment and more studies with a larger sample size and longer duration are required.
Pradhan, Sunil; Tandon, Ruchika
N-hexane neuropathy is an occupational disease caused by exposure to n-hexane, which is used as a solvent in silk screen printing. Here, we describe a 35-year-old man, a silk screen printer by profession, who presented with dizziness, distal swelling of both lower limbs for 10 months and tingling and burning sensation in both feet for 9.5 months along with cold allodynia. The patient had normal results of a motor and sensory system examination, apart from an impaired temperature sense. Nerve conduction tests showed a conduction block in bilateral common peroneal nerves and absence of conduction in bilateral sural nerves. These symptoms resolved when further exposure to n-hexane was ceased but cold allodynia remained. Thus, cold allodynia and impaired temperature sense can be a manifestation of n-hexane neuropathy. Hence, abnormalities on nerve conduction studies can be detected in n-hexane neuropathy patients, even before clinical examination detects any such abnormalities. In the case of the patients presenting with sensory motor neuropathy, history of occupational exposure to n-hexane becomes important, as the sooner the disease is detected, the better the chances of recovery.
Full Text Available Clinical methods of detecting diabetic peripheral neuropathy (DPN are not objective and reproducible. We therefore evaluated if SUDOSCAN, a new method developed to provide a quick, non-invasive and quantitative assessment of sudomotor function can reliably screen for DPN. 70 subjects (45 with type 1 diabetes and 25 healthy volunteers [HV] underwent detailed assessments including clinical, neurophysiological and 5 standard cardiovascular reflex tests (CARTs. Using the American Academy of Neurology criteria subjects were classified into DPN and No-DPN groups. Based on CARTs subjects were also divided into CAN, subclinical-CAN and no-CAN. Sudomotor function was assessed with measurement of hand and foot Electrochemical Skin Conductance (ESC and calculation of the CAN risk score. Foot ESC (μS was significantly lower in subjects with DPN [n = 24; 53.5(25.1] compared to the No-DPN [77.0(7.9] and HV [77.1(14.3] groups (ANCOVA p<0.001. Sensitivity and specificity of foot ESC for classifying DPN were 87.5% and 76.2%, respectively. The area under the ROC curve (AUC was 0.85. Subjects with CAN had significantly lower foot [55.0(28.2] and hand [53.5(19.6] ESC compared to No-CAN [foot ESC, 72.1(12.2; hand ESC 64.9(14.4] and HV groups (ANCOVA p<0.001 and 0.001, respectively. ROC analysis of CAN risk score to correctly classify CAN revealed a sensitivity of 65.0% and specificity of 80.0%. AUC was 0.75. Both foot and hand ESC demonstrated strong correlation with individual parameters and composite scores of nerve conduction and CAN. SUDOSCAN, a non-invasive and quick test, could be used as an objective screening test for DPN in busy diabetic clinics, insuring adherence to current recommendation of annual assessments for all diabetic patients that remains unfulfilled.
Selvarajah, Dinesh; Cash, Tom; Davies, Jennifer; Sankar, Adithya; Rao, Ganesh; Grieg, Marni; Pallai, Shillo; Gandhi, Rajiv; Wilkinson, Iain D; Tesfaye, Solomon
Clinical methods of detecting diabetic peripheral neuropathy (DPN) are not objective and reproducible. We therefore evaluated if SUDOSCAN, a new method developed to provide a quick, non-invasive and quantitative assessment of sudomotor function can reliably screen for DPN. 70 subjects (45 with type 1 diabetes and 25 healthy volunteers [HV]) underwent detailed assessments including clinical, neurophysiological and 5 standard cardiovascular reflex tests (CARTs). Using the American Academy of Neurology criteria subjects were classified into DPN and No-DPN groups. Based on CARTs subjects were also divided into CAN, subclinical-CAN and no-CAN. Sudomotor function was assessed with measurement of hand and foot Electrochemical Skin Conductance (ESC) and calculation of the CAN risk score. Foot ESC (μS) was significantly lower in subjects with DPN [n = 24; 53.5(25.1)] compared to the No-DPN [77.0(7.9)] and HV [77.1(14.3)] groups (ANCOVA p<0.001). Sensitivity and specificity of foot ESC for classifying DPN were 87.5% and 76.2%, respectively. The area under the ROC curve (AUC) was 0.85. Subjects with CAN had significantly lower foot [55.0(28.2)] and hand [53.5(19.6)] ESC compared to No-CAN [foot ESC, 72.1(12.2); hand ESC 64.9(14.4)] and HV groups (ANCOVA p<0.001 and 0.001, respectively). ROC analysis of CAN risk score to correctly classify CAN revealed a sensitivity of 65.0% and specificity of 80.0%. AUC was 0.75. Both foot and hand ESC demonstrated strong correlation with individual parameters and composite scores of nerve conduction and CAN. SUDOSCAN, a non-invasive and quick test, could be used as an objective screening test for DPN in busy diabetic clinics, insuring adherence to current recommendation of annual assessments for all diabetic patients that remains unfulfilled.
Peng, Hui; Chen, Chunli; Cantin, Jenna; Saunders, David M V; Sun, Jianxian; Tang, Song; Codling, Garry; Hecker, Markus; Wiseman, Steve; Jones, Paul D; Li, An; Rockne, Karl J; Sturchio, Neil C; Cai, Minghong; Giesy, John P
The majority of halogenated organic compounds present in the environment remain unidentified. To address this data gap, we recently developed an untargeted method (data-independent precursor isolation and characteristic fragment; DIPIC-Frag) for identification of unknown organo-bromine compounds. In this study, the method was adapted to enable untargeted screening of natural and synthetic organo-iodine compounds (NSOICs) in sediments. A total of 4,238 NSOIC peaks were detected in sediments from Lake Michigan. Precursor ions and formulas were determined for 2,991 (71%) of the NSOIC peaks. These compounds exhibited variations in abundances (<10(3) to ∼10(7)), m/z values (206.9304-996.9474), retention times (1.0-29.7 min), and number of iodine atoms (1-4). Hierarchical cluster analysis showed that sediments in closer proximity exhibited similar profiles of NSOICs. NSOICs were screened in 10 samples of sediment from the Arctic Ocean to compare the profiles of NSOICs between freshwater and marine sediments. A total of 3,168 NSOIC peaks were detected, and profiles of NSOICs in marine sediments were clearly distinct from Lake Michigan. The coexistence of brominated and iodinated analogues indicated that some NSOICs are of natural origin. Different ratios of abundances of iodinated compounds to brominated analogues were observed and proposed as a marker to distinguish sources of NSOICs.
Schneider Fábio K
Full Text Available Abstract Background Autonomic neuropathy is a common and serious complication of diabetes. Early detection is essential to enable appropriate interventional therapy and management. Dynamic pupillometry has been proposed as a simpler and more sensitive tool to detect subclinical autonomic dysfunction. The aim of this study was to investigate pupil responsiveness in diabetic subjects with and without cardiovascular autonomic neuropathy (CAN using dynamic pupillometry in two sets of experiments. Methods During the first experiment, one flash was administered and the pupil response was recorded for 3 s. In the second experiment, 25 flashes at 1-s interval were administered and the pupil response was recorded for 30 s. Several time and pupil-iris radius-related parameters were computed from the acquired data. A total of 24 diabetic subjects (16 without and 8 with CAN and 16 healthy volunteers took part in the study. Results Our results show that diabetic subjects with and without CAN have sympathetic and parasympathetic dysfunction, evidenced by diminished amplitude reflexes and significant smaller pupil radius. It suggests that pupillary autonomic dysfunction occurs before a more generalized involvement of the autonomic nervous system, and this could be used to detect early autonomic dysfunction. Conclusions Dynamic pupillometry provides a simple, inexpensive, and noninvasive tool to screen high-risk diabetic patients for diabetic autonomic neuropathy.
Gulichsen, Elisabeth; Fleischer, Jesper; Ejskjaer, Niels
Cardiac autonomic neuropathy (CAN) is a serious complication of longstanding diabetes and is associated with an increased morbidity and reduced quality of life in patients with diabetes. The present study evaluated the prevalence of CAN diagnosed by reduced heart rate variability (HRV) using...... a newly developed device in a large, unselected, hospital-based population of patients with diabetes....
He, Tianyi; Wang, Chuan; Zuo, Anju; Liu, Pan; Li, Wenjuan
Aims. This study aimed to assess whether the electrochemical skin conductance (ESC) could be used to screen for diabetic cardiac autonomic neuropathy (DCAN) in a Chinese population with diabetes. Methods. We recruited 75 patients with type 2 diabetes mellitus (T2DM) and 45 controls without diabetes. DCAN was diagnosed by the cardiovascular autonomic reflex tests (CARTs) as gold standard. In all subjects ESCs of hands and feet were also detected by SUDOSCAN™ as a new screening method. The efficacy was assessed by receiver operating characteristic (ROC) curve analysis. Results. The ESCs of both hands and feet were significantly lower in T2DM patients with DCAN than those without DCAN (67.33 ± 15.37 versus 78.03 ± 13.73, P = 0.002, and 57.77 ± 20.99 versus 75.03 ± 11.41, P diabetes before further diagnosis with CARTs.
Lechleitner, Monika; Abrahamian, Heidemarie; Francesconi, Claudia; Kofler, Markus
These are the guidelines for diagnosis and treatment of diabetic neuropathy. This diabetic late complication comprises a number of mono- and polyneuropathies, plexopathies, radiculopathies and autonomic neuropathy. The position statement summarizes characteristic clinical symptoms and techniques for diagnostic assessment of diabetic neuropathy. Recommendations for the therapeutic management of diabetic neuropathy, especially for the control of pain in sensorimotor neuropathy, are provided.
... neuropathy are caused by inborn mistakes in the genetic code or by new genetic mutations. × Definition Peripheral neuropathy ... neuropathy are caused by inborn mistakes in the genetic code or by new genetic mutations. View Full Definition ...
Neuropathy - metabolic ... can be caused by many different things. Metabolic neuropathy may be caused by: A problem with the ... one of the most common causes of metabolic neuropathies. People who are at the highest risk for ...
Chen, Allen M., E-mail: email@example.com [Department of Radiation Oncology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, California (United States); Wang, Pin-Chieh [Department of Radiation Oncology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, California (United States); Daly, Megan E.; Cui, Jing; Hall, William H. [Department of Radiation Oncology, University of California, Davis, Comprehensive Cancer Center, Sacramento, California (United States); Vijayakumar, Srinivasan [Department of Radiation Oncology, University of Mississippi School of Medicine, Jackson, Mississippi (United States); Phillips, Theodore L. [Department of Radiation Oncology, University of California, Davis, Comprehensive Cancer Center, Sacramento, California (United States); Farwell, D. Gregory [Department of Otolaryngology–Head and Neck Surgery, University of California, Davis, Comprehensive Cancer Center, Sacramento, California (United States); Purdy, James A. [Department of Radiation Oncology, University of California, Davis, Comprehensive Cancer Center, Sacramento, California (United States)
Purpose: Data from a prospective screening protocol administered for patients previously irradiated for head-and-neck cancer was analyzed to identify dosimetric predictors of brachial plexus-associated neuropathy. Methods and Materials: Three hundred fifty-two patients who had previously completed radiation therapy for squamous cell carcinoma of the head and neck were prospectively screened from August 2007 to April 2013 using a standardized self-administered instrument for symptoms of neuropathy thought to be related to brachial plexus injury. All patients were disease-free at the time of screening. The median time from radiation therapy was 40 months (range, 6-111 months). A total of 177 patients (50%) underwent neck dissection. Two hundred twenty-one patients (63%) received concurrent chemotherapy. Results: Fifty-one patients (14%) reported brachial plexus-related neuropathic symptoms with the most common being ipsilateral pain (50%), numbness/tingling (40%), and motor weakness and/or muscle atrophy (25%). The 3- and 5-year estimates of freedom from brachial plexus-associated neuropathy were 86% and 81%, respectively. Clinical/pathological N3 disease (P<.001) and maximum radiation dose to the ipsilateral brachial plexus (P=.01) were significantly associated with neuropathic symptoms. Cox regression analysis revealed significant dose–volume effects for brachial plexus-associated neuropathy. The volume of the ipsilateral brachial plexus receiving >70 Gy (V70) predicted for symptoms, with the incidence increasing with V70 >10% (P<.001). A correlation was also observed for the volume receiving >74 Gy (V74) among patients treated without neck dissection, with a cutoff of 4% predictive of symptoms (P=.038). Conclusions: Dose–volume guidelines were developed for radiation planning that may limit brachial plexus-related neuropathies.
Evliyaoglu, Ferhat; Karadag, Remzi; Burakgazi, Ahmet Z
Ocular movements and coordination require complex and integrated functions of somatic and autonomic nervous systems. Neurological disorders affecting these nervous systems may cause ocular dysfunction involving extraocular muscles and pupils. In this article, the prevalence, clinical presentations, and management of ocular neuropathy related to certain peripheral neuropathies, including diabetic neuropathy, Guillain-Barré syndrome (GBS), chronic inflammatory neuropathies, human immunodeficiency virus (HIV)-associated neuropathy, and hereditary neuropathies, are examined in detail. Copyright © 2012 Wiley Periodicals, Inc.
COVERED 1 May 201 - 30 Apr 201 4. TITLE AND SUBTITLE : Novel High-Throughput Drug Screening Platform for Chemotherapy-Induced axonal...Introduction-page 1 Results- page 1,2,3 Conclusion-page 3 Introduction: Taxol is an antineoplastic agent, which is used for the treatment of
Blancato, J.; Precht, K.; Meck, J. [Georgetown Univ., Hospital, Washington, DC (United States)] [and others
We assessed the usefulness of in situ hybridization with a DNA probe to the area of chromosome 17 at p11.2 as a diagnostic tool for screening for Charcot Marte Tooth 1A (CMT 1A). In situ hybridization with a probe to 17p11.2 was performed on fixed lymphocytes from the following groups of individuals: (1) normal controls; (2) patients evoking a strong clinical suspicion of CMT 1A; and (3) 3 families with an apparent autosomal dominant peripheral neuropathy of unknown diagnoses. Group 2 patients had evidence of demyelination as defined by nerve conduction of less that 50% of the normal mean or terminal latency greater than 50% of the normal mean in conduction studies. Analysis of interphase cells hybridized with a cosmid DNA probe to 17p11.2 requires inclusion of a normal control with each trial and masked observer. Due to the size of the target DNA and the nature of the centromeric heterochromatin, the scoring of this probe is more subjective than centromere probes. For example, if the two 17 chromosomes are decondensed as in interphase, two tandem signals may be visualized as one. Results from duplication positive patients demonstrate a large proportion of cells with two closely aligned, but separate, signals with an additional single signal. Normal results demonstrate a majority of cells with two separate signals representing both normal homologues. None of the 3 families with questionable diagnosis revealed a duplication at the region, reinforcing our belief that a clinical diagnosis is the most discriminating tool available for diagnosis of CMT 1A. We concur with Boylan that molecular analysis for CMT 1A is useful for establishing a diagnosis of CMT 1A, but is not a primary differential diagnostic test. The yield in screening patients without physiologic evidence of demyelination is likely to be low. We further find that the use of in situ hybridization is a simple method of performing the duplication analysis.
Charles, Morten; Ejskjær, Niels; Witte, Daniel R
OBJECTIVE-There is limited evidence on how intensive multi factorial treatment (IT) improves outcomes of diabetes when initiated in the lead time between detection by screening and diagnosis in routine clinical practice. We examined the effects of early detection and IT of type 2 diabetes...... in primary care on the prevalence of diabetic peripheral neuropathy (DPN) and peripheral arterial disease (PAD) 6 years later in a pragmatic, cluster-randomized parallel group trial. RESEARCH DESIGN AND METHODS-A stepwise screening program in 1.90 general practices in Denmark was used to identify 1...
Ogbera, Anthonia O; Adeleye, Olufunmilayo; Solagberu, Babatunde; Azenabor, Alfred
Identifying the risk factors for diabetes mellitus related foot ulceration would save more limbs from amputation. This report focuses on the determining the burden of peripheral arterial disease and neuropathy in persons with diabetes mellitus (DM). This is a descriptive study carried out in the Diabetic Clinic of the Lagos State University Teaching Hospital in patients with DM who had no past/present history of foot ulceration. Biothesiometry was employed and ankle brachial pressure indices were measured to evaluate for neuropathy and peripheral arterial disease (PAD) respectively. A total of 225 persons living with DM who met inclusion criteria were recruited consecutively over a 3 months period. Age range was 28-87 years with the mean [61.4 (10.8)] and median (63) years respectively. Patients symptomatic for neuropathy and PAD were 37 and 40 % respectively of the study population. An older age of >60 years and poor glycaemic control were potential predictors of neuropathy. Neuropathy and PAD occurred commonly in the seventh decade of life. Given the fairly high proportions of neuropathy and PAD in our patients with DM, we recommend that they be routinely examined in persons with DM.
... can be associated with peripheral neuropathy. Metabolic and endocrine disorders impair the body’s ability to transform nutrients into ... to neuropathies as a result of chemical imbalances. Endocrine disorders that lead to hormonal imbalances can disturb normal ...
Sampaio, Luzia; Silva, Lã Gia; Terroso, Georgina; Nadais, Goreti; Mariz, Eva; Ventura, Francisco
Vasculitic neuropathy corresponds to the occurrence of vasculitis at the level of vasa nervorum, resulting in ischemic damage of the peripheral nerve and axonal degeneration. Vasculitic neuropathy commonly occurs in association with systemic diseases and may be the initial manifestation or arise in the course of established disease. Although rare, vasculitis can be confined to the peripheral nervous system - non-systemic vasculitic neuropathy. This paper aims to review the classification, diagnosis and treatment of vasculitic neuropathy.
Full Text Available Background: Peripheral neuropathy is a common complaint of diabetes. This study aimed to determine the effects of 12 weeks combined training with Vitamin D supplement on improvement of sensory-motor neuropathy in women with diabetic neuropathy. Materials and Methods: This clinical trial study conducted on 90 patients were selected and randomly divided into two groups. Finally, 81 adult females with diabetes type II (20–55 years old were interred in this study. The control group had no training, but received Vitamin D. The experimental group received Vitamin D and 12 weeks training program (3 days a week, 60 min/session including aerobic exercises, strength, and flexibility. Aerobic exercise intensity was set at 60–70% maximum heart rate and resistance training intensity was determined by 10 R.M. Michigan neuropathy questionnaire, reflex hammer and tuning fork 128 Hz used to screening tense of neuropathy (Michigan Neuropathy Screening Instrument that were used for pretest and posttest. Results: Following 3 months combined training and supplementation with Vitamin D, had observed a significant reduction in numbness (P = 0.001, pain (0.002, tingling (P = 0.001, and weakness (P = 0.002 in the lower limb and also increases in sense of touch intervention (P = 0.005, detects the position of the fingers (P = 0.001 and vibration perception (P = 0.001 in tissues. Knee reflexes (P = 0.77 and ankles reflexes (P = 0.47 did not significantly change after interventions. Conclusion: It seems that taking part in combined training and supplementation with Vitamin D can improve the symptoms of sensory-motor neuropathy.
Mah, Jean K; Pacaud, Danièle
The worldwide burden of diabetes and its complications in children continues to increase due to the rise in type 1 and type 2 diabetes. Although overt diabetic neuropathy is rarely present in children and adolescents with diabetes, subclinical diabetic neuropathy has been estimated to occur in approximately half of all children with type 1 diabetes with a duration of 5 years or longer and up to 25% of pediatric patients with newly diagnosed diabetes have abnormal findings on nerve conduction studies. The present review on the state of pediatric diabetic neuropathy covers the definition, prevalence, pathogenesis, diagnosis, risk factors, and possible treatment approaches specific to children and adolescents with diabetes. It also highlights the many unknowns in this field. Nonetheless, new emerging interventions that can either prevent or delay the progression of diabetic microvascular and macrovascular complications may become available in the near future. Until specific interventions for diabetic neuropathy are available for use in children, it will be hard to justify screening for neuropathy other than through clinical assessment. Meanwhile, the search for quicker, easily administered, and quantifiable tests for diabetic neuropathy and efforts to establish valid pediatric norms for well-established measures used in adults will need to continue.
Inflammatory neuropathies are acquired disorders of peripheral nerves and occasionally of the central nervous system that can affect individuals at any age. The course can be monophasic, relapsing, or progressive. Inflammatory neuropathies are classified as acute or chronic. The acute form reaches a nadir by 4 weeks and the chronic form over 8 weeks or greater. The most common example of an acute inflammatory neuropathy is acute inflammatory demyelinating polyradiculoneuropathy (AIDP), which is part of the Guillain-Barré syndrome (GBS). The most common chronic inflammatory neuropathy is chronic inflammatory demyelinating polyradiculopathy (CIDP). Other chronic inflammatory neuropathies are multifocal motor neuropathy (MMN) and the Lewis-Sumner syndrome. The Fisher syndrome and Bickerstaff brainstem encephalitis occur acutely and have clinical overlap with AIDP.
In order to elucidate the physiological significance of autonomic neuropathy in juvenile diabetics, cardiovascular, hormonal and metabolic functions have been investigated in three groups of juvenile diabetics: One group had no signs of neuropathy, one group had presumably slight autonomic...... neuropathy (reduced beat-to-beat variation in heart rate during hyperventilation) and one group had clinically severe autonomic neuropathy, defined by presence of orthostatic hypotension. In all three experimental situations we found sympathetic dysfunction causing cardiovascular and/or hormonal...... maladjustments in patients with autonomic neuropathy. Regarding metabolic functions we found normal responses to graded exercise and insulin-induced hypoglycemia in patients with autonomic neuropathy in spite of blunted catecholamine responses, suggesting increased sensitivity of glycogen stores and adipose...
Inherited neuropathy is a genetically and clinically heterogeneous group of neuropathies, the main category becomes Charcot-Marie-Tooth neuropathy (CMT), also known as hereditary motor and sensory neuropathy (HMSN), distal hereditary motor neuropathy (dHMN), and hereditary sensory autonomic neuropathy (HSAN). At least 80 genes have been associated with CMT, HMN or HSAN, a precise molecular diagnosis is often needed to make a clinical diagnosis accurately, enable genetic counseling of the patient and understanding of their molecular mechanisms. To identify the mutation in each patient, using a high-throughput NGS, we established a diagnostic procedure involving screening of disease causing genes in CMT, HMN or HSAN.
Disulfiram (Antabuse) can produce neuropathy in daily doses of less than the usually recommended 500 mg. The four recent cases reported in this paper emphasize the need for greater recognition of this condition. Nerve biopsies showed axonal degeneration. The neuropathy is difficult to distinguish from that associated with ethanol abuse. Disulfiram neuropathy occurs after a variable latent period (mean 5 to 6 months) and progresses steadily. Slow improvement may occur when the drug's use is st...
Shin, Susan C; Robinson-Papp, Jessica
Peripheral neuropathy is a common complication of many of the systemic amyloidoses. Although the cause of neuropathy is not entirely clear, it is likely related to amyloid deposition within the nerve. This may lead to focal, multifocal, or diffuse neuropathies involving sensory, motor and/or autonomic fibers. The presenting symptoms depend on the distribution of nerves affected. One of the most common phenotypes is sensorimotor polyneuropathy, which is characterized by symptoms of neuropathic pain, numbness, and in advanced cases weakness. Symptoms begin in the feet and ultimately progress to the proximal legs and hands. The most common focal neuropathy is a median neuropathy at the wrist, clinically known as carpal tunnel syndrome. Carpal tunnel symptoms may include pain and sensory disturbances in the lateral palm and fingers; hand weakness may ensue if the focal neuropathy is severe. Autonomic neuropathy may affect a variety of organ systems such as the cardiovascular, gastrointestinal, and genitourinary systems. Symptoms may be non-specific making the diagnosis of autonomic neuropathy more difficult to identify. However, it is important to recognize and distinguish autonomic neuropathy from diseases of the end-organs themselves. This article reviews the inherited and acquired amyloidoses that affect the peripheral nervous system including familial amyloid polyneuropathy, and primary, secondary and senile amyloidosis. We emphasize the clinical presentation of the neurologic aspects of these diseases, physical examination findings, appropriate diagnostic evaluation, treatment and prognosis. © 2012 Mount Sinai School of Medicine.
Siepmann, T; Penzlin, A I; Illigens, B M W
Autonomic neuropathies are a heterogeneous group of diseases that involve damage of small peripheral autonomic Aδ- and C-fibers. Causes of autonomic nerve fiber damage are disorders such as diabetes mellitus and HIV-infection. Predominant symptoms of autonomic neuropathy are orthostatic hypotension, gastro-intestinal problems, urogenital dysfunction, and cardiac arrhythmia, which can severely impair the quality of life in affected patients. Furthermore, autonomic neuropathies can be induced by autoimmune diseases such as acute inflammatory demyelinating polyneuropathy, hereditary disorders such as the lysosomal storage disorder Fabry disease and hereditary sensory and autonomic neuropathies, as well as certain toxins and drugs.
Antoine, Jean-Christophe; Camdessanché, Jean-Philippe
To review recent advances in paraneoplastic neuropathies with emphasis on their definition, different forms and therapeutic development. A strict definition of definite paraneoplastic neuropathies is necessary to avoid confusion. With carcinoma, seronegative sensory neuronopathies and neuronopathies and anti-Hu and anti-CV2/Contactin Response Mediator Protein 5 antibodies are the most frequent. With lymphomas, most neuropathies occur with monoclonal gammopathy including AL amyloidosis, Polyneuropathy-Organomegaly-Endocrinopathy-M component-Skin changes (POEMS) syndrome, type I cryoglobulinemia and antimyelin-associated glycoprotein (MAG) neuropathies and Waldenström's disease. Neuropathies improving with tumor treatment are occasional, occur with a variety of cancer and include motor neuron disease, chronic inflammatory demyelinating neuropathy and nerve vasculitis. If antibodies toward intracellular antigens are well characterized, it is not the case for antibodies toward cell membrane proteins. Contactin-associated protein-2 antibodies occur with neuromyotonia and thymoma with the Morvan's syndrome in addition to Netrin 1 receptor antibodies but may not be responsible for peripheral nerve hyperexcitability. The treatment of AL amyloidosis, POEMS syndrome, anti-MAG neuropathy and cryoglobulinemia is now relatively well established. It is not the case with onconeural antibodies for which the rarity of the disorders and a short therapeutic window are limiting factors for the development of clinical trials. A strict definition of paraneoplastic neuropathies helps their identification and is necessary to allow an early diagnosis of the underlying tumor.
Chudzik, Wiesław; Kaczorowska, Beata; Przybyła, Monika; Chudzik, Bartosz; Gałka, Małgorzata
Diabetic neuropathy is most common chronic complication of diabetes mellitus. It is responsible for substantial morbidity, increased mortality and impaired quality of life. Patogenesis of diabetic neuropathy is complex. Chronic hyperglycemia is a major factor induces nerve fibers injury. High level of glucose stimulate the polyol pathway causing osmotic stress and enhance reactive oxygen species generation, as well as it play an important role in diabetic angiopathy development. Distal symmetric polineuropathy is most common type of diabetic neuropathy. Many patient may develop combinations of neuropathies concerning somatic and autonomic system. Early diagnosis and administered suitable treatment are necessary to reduce severe complication of diabetic neuropathy as well as strict glycemic control and risk factor increased.
Vallat, Jean-Michel; Calvo, Judith; Ghorab, Karima; Tazir, Meriem
Although there are many human hereditary neuropathies, most of them with the exception of Charcot-Marie-Tooth disease or hereditary sensorimotor neuropathy, are rare. Irrespective of their type, the mode of transmission may be autosomal dominant or recessive, or X-linked. The most difficult to diagnose, however, are the sporadic forms. It is customary to distinguish the cases in which the neuropathy is the sole clinical expression from multisystemic diseases where neuropathy is one component of multi-organ involvement. The complexity and the multiplicity of genes involved and the lack of understanding of their exact functions hinder logical presentation of these hereditary neuropathies. For understandable technical reasons, the stage of specific treatment, namely the repair of the mutated gene, has yet to be attained.
Low, P. A.
A limited autonomic neuropathy may underlie some unusual clinical syndromes, including the postural tachycardia syndrome, pseudo-obstruction syndrome, heat intolerance, and perhaps chronic fatigue syndrome. Antibodies to autonomic structures are common in diabetes, but their specificity is unknown. The presence of autonomic failure worsens prognosis in the diabetic state. Some autonomic neuropathies are treatable. Familial amyloid polyneuropathy may respond to liver transplantation. There are anecdotal reports of acute panautonomic neuropathy responding to intravenous gamma globulin. Orthostatic hypotension may respond to erythropoietin or midodrine.
Gwathmey, Kelly Graham; Burns, Ted Michael; Collins, Michael Paul; Dyck, P James Bonham
The vasculitic neuropathies are a diverse group of disorders characterised by the acute-to-subacute onset of painful sensory and motor deficits that result from inflammatory destruction of nerve blood vessels and subsequent ischaemic injury. They are common in patients with primary systemic vasculitis and are seen in vasculitis secondary to disorders such as rheumatoid arthritis, viral infections, and diabetic inflammatory neuropathies. It is imperative that neurologists recognise these disorders to initiate treatment promptly and thereby prevent morbidity and mortality. To simplify the approach to patients with vasculitis of the peripheral nerves, a straightforward, dichotomous classification scheme can be used in which the vasculitic neuropathies are divided into two groups-nerve large arteriole vasculitis and nerve microvasculitis-on the basis of the size of the involved vessels. The size of the affected blood vessels correlates with the clinical course and prognosis in patients with vasculitic neuropathy. Copyright © 2014 Elsevier Ltd. All rights reserved.
... harm. Alpha-lipoic acid Preliminary research suggests this antioxidant may be helpful in slowing or even reversing ... electrical waves transmitted through electrodes placed on the skin, may help ease pain associated with diabetic neuropathy. ...
Waterston, J A; Gilligan, B S
A case of sensory neuropathy in a young woman due to long-term ingestion of pyridoxine, with subsequent recovery, is described. Pyridoxine neuropathy may occur after the long-term ingestion of doses as low as 200 mg a day. Because of its widespread use in the community, both the general public and the medical community need to be aware of this recently described complication of megavitamin therapy.
Izenberg, Aaron; Perkins, Bruce A; Bril, Vera
Diabetes mellitus is a common condition and diabetics are prone to develop a spectrum of neuropathic complications ranging from symmetric and diffuse to asymmetric and focal neuropathies that may be associated with significant morbidity. Diabetic sensorimotor polyneuropathy is the most common of these complications, occurring in patients with type 1 and 2 diabetes mellitus, as well as in those with prediabetes and glucose intolerance. In this review, the authors discuss the wide variety of neuropathies that can present in the context of diabetes, including the clinical manifestations, diagnostic features, and approach to management. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
The diagnosis of autonomic neuropathy is often difficult to establish, since clinical symptoms generally appear late in the course of the disease, and may be non-specific. A number of recently developed quantifiable and reproducible autonomic nerve function tests are reviewed, with emphasis on th...
Hanewinckel, R; Ikram, M A; Van Doorn, P A
Peripheral neuropathies are diseases of the peripheral nervous system that can be divided into mononeuropathies, multifocal neuropathies, and polyneuropathies. Symptoms usually include numbness and paresthesia. These symptoms are often accompanied by weakness and can be painful. Polyneuropathies can be divided into axonal and demyelinating forms, which is important for diagnostic reasons. Most peripheral neuropathies develop over months or years, but some are rapidly progressive. Some patients only suffer from mild, unilateral, slowly progressive tingling in the fingers due to median nerve compression in the wrist (carpal tunnel syndrome), while other patients can be tetraplegic, with respiratory insufficiency within 1-2 days due to Guillain-Barré syndrome. Carpal tunnel syndrome, with a prevalence of 5% and incidence of 1-2 per 1000 person-years, is the most common mononeuropathy. Population-based data for chronic polyneuropathy are relatively scarce. Prevalence is estimated at 1% and increases to 7% in persons over 65 years of age. Incidence is approximately 1 per 1000 person-years. Immune-mediated polyneuropathies like Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy are rare diseases, with an annual incidence of approximately 1-2 and 0.2-0.5 per 100 000 persons respectively. Most peripheral neuropathies are more prevalent in older adults and in men, except for carpal tunnel syndrome, which is more common in women. Diabetes is a common cause of peripheral neuropathy and is associated with both mono- and polyneuropathies. Among the group of chronic polyneuropathies, in about 20-25% no direct cause can be found. These are slowly progressive axonal polyneuropathies. © 2016 Elsevier B.V. All rights reserved.
Full Text Available Background and Objective: Diabetes is associated with many complications that one of these complications is neuropathy. This disease is more common in women. In cases of self-care deficit and not meeting its related needs, the disease can lead to complications and even death. This study was done to determine the self care ability of diabetes women with peripheral neuropathy and its related need based on Orem self care model. Materials and Method: This cross - sectional study was conducted on women with diabetic peripheral neuropathy who referred to diabetes clinic in one of the hospitals in Gonabad in 2014. 120 patients were selected by convenience sampling. Patients’ neuropathy was determined by Michigan Neuropathy Screening Instrument and Toronto Clinical Neuropathy Score. Then, data were gathered through using self care needs assessment questionnaire and self care ability questionnaire based on Orem self care model. Data analysis was done through using descriptive statistical test and chi-square test with in SPSS 17. Results: The self care ability of 71.7 percent of patients was weak (33.72 ± 8.48 and according to needs assessment and in domains of knowledge, attitude and performance, 10.8, 0.8 and 52.5 percent of subjects were weak respectively. Conclusion: According to the findings, the self care ability of diabetic women with peripheral neuropathy was weak. The domain of performance was weaker than attitude and knowledge domains concerning the self care ability. Therefore, it is recommended to design and implement of necessary measures for improving the patients’ self care ability based on their needs.
Ensrud, E R; Krivickas, L S
The acquired demyelinating neuropathies can be divided into those with an acute onset and course and those with a more chronic course. The acute neuropathies present as Guillain-Barré syndrome and include acute inflammatory demyelinating polyradiculoneuropathy (AIDP), Miller Fisher syndrome, acute motor axonal neuropathy (AMAN), acute motor and sensory axonal neuropathy (AMSAN), and acute pandysautonomia. The chronic neuropathies are collectively known as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and include MADSAM (multifocal acquired demyelinating sensory and motor neuropathy, also know as Lewis-Sumner syndrome) and DADS (distal acquired demyelinating symmetric neuropathy) as variants. The clinical features, pathology, pathogenesis, diagnosis, treatment, rehabilitation, and prognosis of these neuropathies are discussed.
Kuntzer, Thierry; Chofflon, Michel
Inflammatory neuropathies include those neuropathies in which the diagnosis, outcome and type of treatment are badly known, the reason of this review. They are expressed as diffuse (such as CIDP and ganglionopathies), multifocal (vasculitic neuropathy) or focal (MMN; plexopathies; immune reconstitution inflammatory syndrome). These forms of neuropathies are important to be known because the beneficial therapeutic possibilities of immunosuppression.
Diabetes mellitus is the commonest cause of an autonomic neuropathy in the developed world. Diabetic autonomic neuropathy causes a constellation of symptoms and signs affecting cardiovascular, urogenital, gastrointestinal, pupillomotor, thermoregulatory, and sudomotor systems. Several discrete syndromes associated with diabetes cause autonomic dysfunction. The most prevalent of these are: generalized diabetic autonomic neuropathy, autonomic neuropathy associated with the prediabetic state, treatment-induced painful and autonomic neuropathy, and transient hypoglycemia-associated autonomic neuropathy. These autonomic manifestations of diabetes are responsible for the most troublesome and disabling features of diabetic peripheral neuropathy and result in a significant proportion of the mortality and morbidity associated with the disease.
Ali, Raymond Azman
Diabetes mellitus is the commonest cause of neuropathy worldwide. Diabetic neuropathy (DN) develops in about 4–10% of diabetic patients after 5 years and in 15% after 20 years. Four main mechanisms have been postulated to underlie the pathogenesis of DN. Diabetic neuropathy can be divided into symmetrical and asymmetrical neuropathies. Diabetic Autonomic Neuropathy (DAN) parallels the severity of DSN, and affects primarily the cardiovascular, gastrointestinal, genitourinary and integumentary ...
Rahmani Katigari, Meysam; Ayatollahi, Haleh; Malek, Mojtaba; Kamkar Haghighi, Mehran
To design a fuzzy expert system to help detect and diagnose the severity of diabetic neuropathy. The research was completed in 2014 and consisted of two main phases. In the first phase, the diagnostic parameters were determined based on the literature review and by investigating specialists' perspectives (n = 8). In the second phase, 244 medical records related to the patients who were visited in an endocrinology and metabolism research centre during the first six months of 2014 and were primarily diagnosed with diabetic neuropathy, were used to test the sensitivity, specificity, and accuracy of the fuzzy expert system. The final diagnostic parameters included the duration of diabetes, the score of a symptom examination based on the Michigan questionnaire, the score of a sign examination based on the Michigan questionnaire, the glycolysis haemoglobin level, fasting blood sugar, blood creatinine, and albuminuria. The output variable was the severity of diabetic neuropathy which was shown as a number between zero and 10, had been divided into four categories: absence of the disease, (the degree of severity) mild, moderate, and severe. The interface of the system was designed by ASP.Net (Active Server Pages Network Enabled Technology) and the system function was tested in terms of sensitivity (true positive rate) (89%), specificity (true negative rate) (98%), and accuracy (a proportion of true results, both positive and negative) (93%). The system designed in this study can help specialists and general practitioners to diagnose the disease more quickly to improve the quality of care for patients.
Xiaobo Li; Kun Xia; Beisha Tang; Ruxu Zhang; Xiaohong Zi; Lin Li; Yajing Zhan; Shunxiang Huang; Jin Li; Xuning Li; Xigui Li; Zhengmao Hu
We used the allele-specific PCR-double digestion method on peripheral myelin protein 22 (PMP22) to determine duplication and deletion mutations in the proband and family members of one family with Charcot-Marie-Tooth disease type 1 and one family with hereditary neuropathy with liability to pressure palsies. The proband and one subclinical family member from the Charcot-Marie-Tooth disease type 1 family had a PMP22 gene duplication; one patient from the hereditary neuropathy with liability to pressure palsies family had a PMP22 gene deletion. Electron microscopic analysis of ultrathin sections of the superficial peroneal nerve from the two probands demonstrated demyelination and myelin sheath hyperplasia, as well as an ‘onion-like’ structure in the Charcot-Marie-Tooth disease type 1A patient. We observed an irregular thickened myelin sheath and ‘mouse-nibbled’-like changes in the patient with hereditary neuropathy with liability to pressure palsies. In the Charcot-Marie-Tooth disease type 1A patient, nerve electrophysiological examination revealed moderate-to-severe reductions in the motor and sensory conduction velocities of the bilateral median nerve, ulnar nerve, tibial nerve, and sural nerve. Moreover, the compound muscle action potential amplitude was decreased. In the patient with hereditary neuropathy with liability to pressure palsies, the nerve conduction velocity of the bilateral tibial nerve and sural nerve was moderately reduced, and the nerve conduction velocity of the median nerve and ulnar nerve of both upper extremities was slightly reduced.
From the perspective of neuropathies with an acute onset mimicking that of Guillain-Barré syndrome (GBS), cases with profound sensory and/or autonomic impairment without any significant weakness have been reported. Although the possibility of infectious or toxic etiologies should be carefully excluded, immune mechanisms similar to those in GBS are suggested to be involved in these so-called acute sensory neuropathies and acute autonomic neuropathies. The types of neuropathy include those with predominant sensory manifestations, predominant autonomic manifestations such as autoimmune autonomic ganglionopathy, and both sensory and autonomic manifestations such as acute autonomic and sensory neuropathy. Neuronopathy in the sensory and/or autonomic ganglia (i.e., ganglionopathy) has been commonly suggested in patients with these types of neuropathies. The presence of Anti-GD1b antibodies has been reported in some of the patients with acute sensory neuropathy with deep sensory impairment, whereas anti-ganglionic acetylcholine receptor antibodies are reported to be present in half of the patients with autoimmune autonomic ganglionopathy. The discovery of anti-ganglionic acetylcholine receptor antibodies significantly expanded the spectrum of autoimmune autonomic ganglionopathy. This is because some of the patients with chronic progression mimicking neurodegenerative diseases such as pure autonomic failure were positive for these antibodies. In contrast, pathologically significant autoantibodies have not been identified in acute autonomic and sensory neuropathy. Further studies are needed to clarify the pathogenesis and the spectrum of these types of neuropathies.
Assal, J.P.; Liniger, C.
The authors present results and experience in sixteen specific disciplines related to the study of nerve physiopathology, diagnosis and treatment. Twenty-two different peripheral neuropathies are presented, and different models related to health care strategies are discussed. The authors report on Inflammatory and autoimmune neuropathies and Genetic neuropathies.
Laughlin, Ruple S; Dyck, P James B
Diabetic radiculoplexus neuropathies (DRPN) are neuropathies clinically and pathologically distinct from the neuropathy typically associated with diabetes (DPN). DRPN are usually subacute in onset, painful, and often demonstrate a monophasic course with incomplete recovery. Pathologically, these neuropathies are due to ischemic injury from altered immunity and often have features suggestive or diagnostic of microvasculitis. Unlike DPN, immune therapy may be helpful in treatment of these conditions given their pathological substrate and therefore are important to identify early and distinguish from other neuropathies that occur in patient with diabetes.
Kim, Eun Sook; Lee, Sung Won; Mo, Eun Young; Moon, Sung Dae; Han, Je Ho
Several studies have suggested that bilirubin, a potent innate antioxidant, plays a protective role against cardiovascular and microvascular disease. This study investigated the association between serum concentrations of total bilirubin (TB) and the presence of diabetic peripheral neuropathy (DPN) in Korean diabetic patients. This cross-sectional study involved 1207 patients aged more than 30 years with type 2 diabetes. DPN was assessed according to clinical symptoms and physical examinations using Michigan Neuropathy Screening Instrument examination score, 10-g monofilament sensation, and current perception threshold. The subjects were stratified into gender-specific tertiles based on TB values, and the relationship between the TB values and DPN was analyzed. Compared with patients within the lowest TB tertile, those with higher TB levels consisted of patients with shorter duration of diabetes, lower HbA1c, better renal function, and less autonomic neuropathy, retinopathy, and albuminuria. Serum TB levels were inversely associated with DPN. In multivariate analysis for the development of DPN after adjusting for potential confounding factors including retinopathy, albuminuria, and autonomic neuropathy, the TB levels were inversely associated with the presence of DPN, both as a continuous variable [odds ratio (OR) per log standard deviation (SD) 0.79; 95% confidence interval (CI) 0.65-0.97; P = 0.022] and when categorized in tertiles (the highest vs. the lowest tertile; OR 0.63; 95% CI 0.40-0.99; P = 0.046). Low serum bilirubin levels are significantly associated with DPN, independently of classic risk factors and other microvascular complications. Further investigation is necessary to determine whether serum bilirubin has a prognostic significance on DPN.
Full Text Available Abstract Background Diabetes mellitus type II afflicts at least 2 million people in Iran. Neuropathy is one of the most common complications of diabetes and lowers the patient's quality of life. Since neuropathy often leads to ulceration and amputation, we have tried to elucidate the factors that can affect its progression. Methods In this case-control study, 110 diabetic patients were selected from the Shariati Hospital diabetes clinic. Michigan Neuropathic Diabetic Scoring (MNDS was used to differentiate cases from controls. The diagnosis of neuropathy was confirmed by nerve conduction studies (nerve conduction velocity and electromyography. The multiple factors compared between the two groups included consumption of angiotensin converting enzyme inhibitors (ACEI, blood pressure, serum lipid level, sex, smoking, method of diabetes control and its quality. Results Statistically significant relationships were found between neuropathy and age, gender, quality of diabetes control and duration of disease (P values in the order: 0.04, 0.04, Conclusion In this study, hyperglycemia was the only modifiable risk factor for diabetic neuropathy. Glycemic control reduces the incidence of neuropathy, slows its progression and improves the diabetic patient's quality of life. More attention must be paid to elderly male diabetic patients with poor diabetes control with regard to regular foot examinations and more practical education.
Margaritidis, Charalambos; Kontoninas, Zisis; Stergiou, Ioannis; Tsotoulidis, Stefanos; Karlafti, Eleni; Mourouglakis, Alexandros; Hatzitolios, Apostolos I.
Aim. To evaluate the effect of quinapril on diabetic cardiovascular autonomic neuropathy (CAN) and peripheral neuropathy (DPN). Patients and Methods. Sixty-three consecutive patients with diabetes mellitus [43% males, 27 with type 1 DM, mean age 52 years (range 22–65)], definite DCAN [abnormal results in 2 cardiovascular autonomic reflex tests (CARTs)], and DPN were randomized to quinapril 20 mg/day (group A, n = 31) or placebo (group B, n = 32) for 2 years. Patients with hypertension or coronary heart disease were excluded. To detect DPN and DCAN, the Michigan Neuropathy Screening Instrument Questionnaire and Examination (MNSIQ and MNSIE), measurement of vibration perception threshold with biothesiometer (BIO), and CARTs [R-R variation during deep breathing [assessed by expiration/inspiration ratio (E/I), mean circular resultant (MCR), and standard deviation (SD)], Valsalva maneuver (Vals), 30 : 15 ratio, and orthostatic hypotension (OH)] were used. Results. In group A, E/I, MCR, and SD increased (p for all comparisons diabetic patients. PMID:28373993
Gess, B; Schirmacher, A; Young, P
Hereditary neuropathies belong to the most common neurogenetic disorders. They appear mostly as sensory and motor neuropathies but there are also pure sensory, pure motor as well as sensory and autonomic hereditary neuropathies. In clinical practice, knowledge of hereditary neuropathies is important in order to recognize them among polyneuropathies and achieve a successful genetic diagnosis. The molecular genetics of hereditary neuropathies are very heterogeneous with currently more than 40 known disease-causing genes. The 4 most common genes account for almost 90% of the genetically diagnosed hereditary neuropathies. In this review article we provide an overview of the currently known genes and propose a rational genetic work-up protocol of the most common genes.
National Oceanic and Atmospheric Administration, Department of Commerce — Bathymetry of Lake Michigan has been compiled as a component of a NOAA project to rescue Great Lakes lake floor geological and geophysical data and make it more...
Hansen, C.S.; Jensen, T.M.; Jensen, J.S.
AIMS: Cardiovascular autonomic neuropathy and diabetic peripheral neuropathy are common diabetic complications and independent predictors of cardiovascular disease. The glucose metabolite methylglyoxal has been suggested to play a causal role in the pathogeneses of diabetic peripheral neuropathy...... and possibly diabetic cardiovascular autonomic neuropathy. The aim of this study was to investigate the cross-sectional association between serum methylglyoxal and diabetic peripheral neuropathy and cardiovascular autonomic neuropathy in a subset of patients in the ADDITION-Denmark study with short-term screen......-detected Type 2 diabetes (duration ~ 5.8 years). METHODS: The patients were well controlled with regard to HbA(1c), lipids and blood pressure. Cardiovascular autonomic neuropathy was assessed by measures of resting heart rate variability and cardiovascular autonomic reflex tests. Diabetic peripheral neuropathy...
Hansen, C.S.; Jensen, T.M.; Jensen, J.S.
AIMS: Cardiovascular autonomic neuropathy and diabetic peripheral neuropathy are common diabetic complications and independent predictors of cardiovascular disease. The glucose metabolite methylglyoxal has been suggested to play a causal role in the pathogeneses of diabetic peripheral neuropathy...... and possibly diabetic cardiovascular autonomic neuropathy. The aim of this study was to investigate the cross-sectional association between serum methylglyoxal and diabetic peripheral neuropathy and cardiovascular autonomic neuropathy in a subset of patients in the ADDITION-Denmark study with short-term screen......-detected Type 2 diabetes (duration ~ 5.8 years). METHODS: The patients were well controlled with regard to HbA(1c), lipids and blood pressure. Cardiovascular autonomic neuropathy was assessed by measures of resting heart rate variability and cardiovascular autonomic reflex tests. Diabetic peripheral neuropathy...
Saporta, Mario A.; Shy, Michael E.
SYNOPSIS Charcot Marie Tooth disease (CMT) is a heterogeneous group of inherited peripheral neuropathies in which the neuropathy is the sole or primary component of the disorder, as opposed to diseases in which the neuropathy is part of a more generalized neurological or multisystem syndrome. Due to the great genetic heterogeneity of this condition, it can be challenging for the general neurologist to diagnose patients with specific types of CMT. Here, we review the biology of the inherited peripheral neuropathies, delineate major phenotypic features of the CMT subtypes and suggest strategies for focusing genetic testing. PMID:23642725
Rahmani Katigari, Meysam; Ayatollahi, Haleh; Malek, Mojtaba; Kamkar Haghighi, Mehran
AIM To design a fuzzy expert system to help detect and diagnose the severity of diabetic neuropathy. METHODS The research was completed in 2014 and consisted of two main phases. In the first phase, the diagnostic parameters were determined based on the literature review and by investigating specialists’ perspectives (n = 8). In the second phase, 244 medical records related to the patients who were visited in an endocrinology and metabolism research centre during the first six months of 2014 and were primarily diagnosed with diabetic neuropathy, were used to test the sensitivity, specificity, and accuracy of the fuzzy expert system. RESULTS The final diagnostic parameters included the duration of diabetes, the score of a symptom examination based on the Michigan questionnaire, the score of a sign examination based on the Michigan questionnaire, the glycolysis haemoglobin level, fasting blood sugar, blood creatinine, and albuminuria. The output variable was the severity of diabetic neuropathy which was shown as a number between zero and 10, had been divided into four categories: absence of the disease, (the degree of severity) mild, moderate, and severe. The interface of the system was designed by ASP.Net (Active Server Pages Network Enabled Technology) and the system function was tested in terms of sensitivity (true positive rate) (89%), specificity (true negative rate) (98%), and accuracy (a proportion of true results, both positive and negative) (93%). CONCLUSION The system designed in this study can help specialists and general practitioners to diagnose the disease more quickly to improve the quality of care for patients. PMID:28265346
Full Text Available Bogdan Timar,1 Romulus Timar,2 Adalbert Schiller,2 Cristian Oancea,3 Deiana Roman,1 Mihaela Vlad,2 Bogdan Balinisteanu,4 Octavian Mazilu5 1Department of Functional Sciences, 2Second Department of Internal Medicine, 3Department of Infectious Diseases, 4Department of Microscopic Morphology, 5First Department of Surgery, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania Purpose: The purpose of this study was to evaluate the impact of the presence and severity of neuropathy and depression on the patient’s adherence to diabetes-related self-care activities (DRSCA in a cohort of patients with type 2 diabetes mellitus (T2DM.Patients and methods: In this cross-sectional, noninterventional study, 198 patients with T2DM were enrolled according to a population-based, consecutive-case enrollment principle. In all patients, the adherence to DRSCA was evaluated using the Summary of Diabetes Self-Care Activities (SDSCA questionnaire; a higher SDSCA score is associated with a better adherence. The presence and severity of neuropathy was assessed using the Michigan Neuropathy Screening Instrument (MNSI and the severity of depression using the Patient Health Questionnaire-9 (PHQ-9.Results: The presence of neuropathy was associated with a decreased SDSCA score (26 points vs 37 points; P<0.001, an increased severe depression prevalence (24.7% vs 4.3%; P<0.001, and an increased PHQ-9 score (12 points vs 7 points; P<0.001. The MNSI score was reverse correlated with SDSCA score (r=-0.527; P<0.001 and positively correlated with PHQ-9 score (r=0.495; P<0.001. The reverse correlation between MNSI score and SDSCA score was present for all the subcomponents of SDSCA questionnaire (diet, exercise, glycemic monitoring, and foot care.Conclusion: The presence of neuropathy is associated with decreases in the quality of adherence to DRSCA in patients with T2DM and with increases in the symptomatology of depression. The significant, negative
Milea, Dan; Amati-Bonneau, Patrizia; Reynier, Pascal
The present review focuses on recent advances in the knowledge of hereditary optic neuropathies resulting from retinal ganglion cell degeneration, mostly due to mitochondrial dysfunctions.......The present review focuses on recent advances in the knowledge of hereditary optic neuropathies resulting from retinal ganglion cell degeneration, mostly due to mitochondrial dysfunctions....
G, Amruth; S, Praveen-kumar; B, Nataraju; BS, Nagaraja
Background: In the era of highly active antiretroviral therapy, sensory neuropathies have increased in prevalence. We have documented the frequency and profile of the two most common forms of sensory neuropathies associated with Human Immunodeficiency Virus (HIV) infection and looked into clinicoelectrophysiological correlates to differentiate the two entities.
Valentina Van Boekel
Full Text Available Peripheral neuropathy is a rare manifestation in hyperthyroidism. We describe the neurological manifestations of a 38 year old female with Graves' disease who developed peripheral neuropathy in the course of her treatment with propylthiouracil. After the drug was tapered off, the neurological signs disappeared. Therefore, we call attention for a possible toxic effect on peripheral nervous system caused by this drug.
Rafael, Benoliel; Sorin, Teich; Eli, Eliav
This article discusses neuropathic pain of traumatic origin affecting the trigeminal nerve. This syndrome has been termed painful traumatic trigeminal neuropathy by the International Headache Society and replaces atypical odontalgia, deafferentation pain, traumatic neuropathy, and phantom toothache. The discussion emphasizes the diagnosis and the early and late management of injuries to the trigeminal nerve and subsequent painful conditions.
Sawicka-Pierko, Anna; Obuchowska, Iwona; Mariak, Zofia
Nutritional optic neuropathy (aka deficiency optic neuropathy) is a dysfunction of the optic nerve resulting from improper dietary content of certain nutrients essential for normal functioning of the nerve fibers. Most commonly, it results from folic acid and vitamin B complex deficiency associated with malnutrition or poor dietary habits, incorrectly applied vegetarian diet, or chronic alcohol abuse. Obese patients after bariatric surgery constitute another risk group of optic neuropathy. Nutritional optic neuropathy is characterized by painless, gradually progressing, bilateral and symmetrical decrease in visual acuity, which can be accompanied by the color vision dysfunction. Progression of the neuropathy is associated with optic nerve atrophy, manifesting as complete disc pallor. Treatment of nutritional neuropathy includes dietary supplementation, aimed at compensating for the deficient nutrients. The treatment is mostly based on folic acid, vitamin B complex, and protein replacement, as well as eliminating risk factors of neuropathy. Early treatment commencement, prior to irreversible optic nerve atrophy, is a prerequisite of effective treatment. We would like to highlight this problem by presenting the case of a young woman in whom chronic use "water-based" diet resulted in anemia and bilateral nutritional optic neuropathy.
Milea, Dan; Amati-Bonneau, Patrizia; Reynier, Pascal
The present review focuses on recent advances in the knowledge of hereditary optic neuropathies resulting from retinal ganglion cell degeneration, mostly due to mitochondrial dysfunctions.......The present review focuses on recent advances in the knowledge of hereditary optic neuropathies resulting from retinal ganglion cell degeneration, mostly due to mitochondrial dysfunctions....
@@Diabetic neuropathy (DN) is one of the common complications of diabetes mellitus (DM), its incidence can be as high as over 90%. The lesion can involve the sensory, motor and vegetative nerves. As a whole, the lesion can be divided into symmetric multiple neuropathy and asymmetric single neuropathy. Because the pathogenesis of the disease is not clear, no specific therapy is available so far. Besides control of blood sugar level, vitamin B, vasodilators and analgesics are often used in Western medicine for expectant treatment. Basic studies on chronic complications of DM show that aldose reductase and non-enzymatic glycosylation of protein are factors initiating the pathological changes, inhibitors against them have been tested in experimental studies and proved effective. Unfortunately, they are not used clinically due to severe side effects. Screening for herbal drugs to treat DN is still a popular trend in the TCM circle.
Léger, Jean-Marc; Guimarães-Costa, Raquel; Muntean, Cristina
Immunotherapy has been investigated in a small subset of peripheral neuropathies, including an acute one, Guillain-Barré syndrome, and 3 chronic forms: chronic inflammatory demyelinating polyradiculoneuropathy, multifocal motor neuropathy, and neuropathy associated with IgM anti-myelin-associated glycoprotein. Several experimental studies and clinical data are strongly suggestive of an immune-mediated pathogenesis. Either cell-mediated mechanisms or antibody responses to Schwann cell, compact myelin, or nodal antigens are considered to act together in an aberrant immune response to cause damage to peripheral nerves. Immunomodulatory treatments used in these neuropathies aim to act at various steps of this pathogenic process. However, there are many phenotypic variants and, consequently, there is a significant difference in the response to immunotherapy between these neuropathies, as well as a need to improve our knowledge and long-term management of chronic forms.
Stoll, G; Reiners, K
The Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are the most common immune-mediated polyneuropathies, which can show variable clinical and electrophysiological manifestations. Rarer immune-mediated neuropathies encompass paraproteinemic neuropathies (PPN), multifocal motor neuropathy (MMN) and vasculitic neuropathies. The diagnosis usually relies on the history of symptom evolution, distribution of nerve dysfunction and particularly on characteristic features in nerve conduction studies, aided by cerebrospinal fluid (CSF) examination and nerve biopsy findings. The therapeutic toolbox encompasses corticosteroids, immunoglobulins and plasmapheresis often accompanied by long-term immunosuppression. It is important to note that immune-mediated neuropathies selectively respond to treatment and contraindications need to be considered. Despite treatment a considerable number of patients suffer from permanent neurological deficits.
Hereditary sensorimotor neuropathies, or Charcot-Marie-Tooth disease (CMT) comprise a group of diseases with heterogeneous clinical, electrophysiological and genetic expression. They are classified by the mode of inheritance (autosomal dominant, X-linked dominant, autosomal recessive) and their electrophysiological characteristics taking into account the speed of motor conduction of the median nerve (demyelinating, intermediary and axonal forms). Certain purely motor forms are called spinal CMT or hereditary distal motor neuropathy, or distal spinal amyotrophy. CMT involving an important sensorial component, trophic disorders, or signs of dysautonomia are included in the classification of hereditary sensory and autonomic neuropathies.
Milea, D; Verny, C
Hereditary optic neuropathies are a group of heterogeneous conditions affecting both optic nerves, with an autosomal dominant, autosomal recessive, X-related or mitochondrial transmission. The two most common non-syndromic hereditary optic neuropathies (Leber's hereditary optic neuropathy and autosomal dominant optic atrophy) are very different in their clinical presentation and their genetic transmission, leading however to a common, non-specific optic nerve atrophy. Beyond the optic atrophy-related visual loss, which is the clinical hallmark of this group of diseases, other associated neurological signs are increasingly recognized.
Goenner, James N.
Michigan's former governor, John Engler, was naturally attracted to charter schools. He had seen for too long how school districts treated students as their property and the state as an endless funding source, and he wanted that to change. Engler saw the chartering strategy as a politically viable means for gaining leverage over school districts…
Smith, Alexander H.
Studies have continued on the diversity of the Michigan bolete flora. During the season of 1972 a variety of Boletus affinis Peck having a reticulate stipe was discovered and abundant material of Boletus bicolor var. subreticulatus Smith & Thiers was obtained. Boletus hortonii Smith & Thiers was col
... normally. A woman may have difficulty with arousal, lubrication, or orgasm. Sweat Glands Autonomic neuropathy can affect ... performed in people with diabetes. Comprehensive foot care programs can reduce amputation rates by 45 to 85 ...
Fleming, Fiona J; Vytopil, Michal; Chaitow, Jeffrey; Jones, H Royden; Darras, Basil T; Ryan, Monique M
Thalidomide was withdrawn from world markets in 1961 following recognition of its teratogenic effects. More recently, however, thalidomide treatment has been reintroduced to adult and paediatric practice for a variety of dermatologic, immunologic, rheumatologic and neoplastic disorders. Neuropathy is a significant side effect of thalidomide therapy, which may limit its clinical use. We report four cases of sensorimotor axonal neuropathy in children aged 10-15 years, treated with thalidomide for myxopapillary ependymoma, Crohn's disease and recurrent giant aphthous ulceration. Thalidomide neuropathy is often associated with proximal weakness and may progress even after discontinuation of treatment, in the phenomenon of 'coasting'. Children treated with thalidomide should undergo regular neurophysiologic studies in order to detect presymptomatic or progressive peripheral neuropathy.
Ross, Mark A
Electrodiagnostic studies are an important component of the evaluation of patients with suspected peripheral nerve disorders. The pattern of findings and the features that are seen on the motor and sensory nerve conduction studies and needle electromyography can help to identify the type of neuropathy, define the underlying pathophysiology (axonal or demyelinating), and ultimately help to narrow the list of possible causes. This article reviews the electrodiagnostic approach to and interpretation of findings in patients with peripheral neuropathies.
王秋菊; 顾瑞; 曹菊阳
evidence of peripheral neuropathy at the time of this writing. Conclusions: In this study, patients with feature of non- syndromic hereditary auditory neuropathy were identified in three Chinese families.Pedigree analysis indicates autosomal recessive inheritances in the pedigrees. The observed inheritance and clinical audiologic findings are different from those previously described for non-syndromic low-frequency sensorineural hearing loss. This information should facilitate future molecular candidate genes screening for understanding the mechanism of AN.
Brannagan, Thomas H
Twenty million people in the United States are estimated to have peripheral neuropathy. However, many patients are not aware of their diagnosis, are not given the diagnosis or being treated, or the diagnosis is delayed. Currently, the only treatments available for neuropathy are aimed at treating the underlying medical conditions that cause the neuropathy or treating symptoms such as pain. Neither treats the actual nerve fiber dysfunction or fiber loss, or helps nerve fibers regenerate. Idiopathic neuropathy, that is neuropathy for which a cause is not identified, is common, accounting in referral series for 25% in all neuropathy patients and 50% or more of patients with small fiber neuropathy. Currently, there is only one FDA-approved medication for a specific neuropathy (chronic inflammatory demyelinating polyneuropathy) while there are two FDA approved medications for diabetic neuropathy pain and four that are approved for post-herpetic neuralgia pain. For many patients with painful neuropathy, these medications are ineffective or not tolerated. Continued research into the underlying mechanisms of neuropathy and an increased understanding of nerve regeneration and neuropathic pain are needed to address this unmet medical need among patients with neuropathy.
The more frequent entrapment neuropathies related to sport are described: thoracic outlet syndrome in aquatic athletes and pitchers, long thoracic neuropathy in tennis players, suprascapular neuropathy in volleyball and tennis players, ulnar nerve entrapment at the elbow in pitchers and at the wrist in cyclists, Morton's syndrome in runners and dancers. Peer reviewed
Deli, Gabriella; Bosnyak, Edit; Pusch, Gabriella; Komoly, Samuel; Feher, Gergely
Changes in human behaviour and lifestyle over the last century have resulted in a dramatic increase in the incidence of diabetes worldwide. Neuropathy is a common and costly complication of both type 1 and type 2 diabetes. The prevalence of neuropathy is estimated to be about 8% in newly diagnosed patients and greater than 50% in patients with long-standing disease. There are two main types of diabetic neuropathies, named as sensorimotor and autonomic neuropathies. Sensorimotor neuropathy is marked by pain, paraesthesia and sensory loss, and autonomic neuropathy may contribute to myocardial infarction, malignant arrhythmia and sudden death. In this article we reviewed the pathogenesis, clinical manifestations diagnosis and treatment of diabetic neuropathies. Sensorimotor and autonomic neuropathies (cardiovascular, gastrointestinal and genitourinary autonomic neuropathies) are common in diabetic patients. Apart from strict glycaemic control, no further therapeutic approach exists in the prevention of this phenomenon. Intensive diabetes therapy, intensive multifactorial cardiovascular risk reduction and lifestyle intervention are recommended in patients with cardiovascular autonomic neuropathy. Gastroparesis is the most debilitating complication of gastrointestinal autonomic neuropathy and genitourinary autonomic neuropathy can cause sexual dysfunction and neurogenic bladder; these conditions are hard to manage. The symptomatic treatment of sensory symptoms includes tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors, gabapentin, pregabalin and opioids. Other treatment strategies are not so effective. © 2013 S. Karger AG, Basel.
Eckhoff, Lise; Feddersen, Søren; Knoop, Ann
Background. Docetaxel is a highly effective treatment of a wide range of malignancies but is often associated with peripheral neuropathy. The genetic variability of genes involved in the transportation or metabolism of docetaxel may be responsible for the variation in docetaxel-induced peripheral...... neuropathy (DIPN). The main purpose of this study was to investigate the impact of genetic variants in GSTP1 and ABCB1 on DIPN. Material and methods. DNA was extracted from whole blood from 150 patients with early-stage breast cancer who had received adjuvant docetaxel from February 2011 to May 2012. Two...
The main lesions of sensory ataxic neuropathy such as chronic idiopathic sensory ataxic neuropathy, (ISAN), carcinomatous neuropathy, Sjögren syndrome-associated neuropathy and acute autonomic and sensory neuropathy (AASN) are the large-diameter sensory neurons and dosal column of the spinal cord and the large myelinated fibers in the peripheral nerve trunks. In addition, afferent fibers to the Clarke's nuclei are also severely involved, suggesting Ia fibers being involved in these neuropathies. In NT-3 knockout mouse, an animal model of sensory ataxia, large-sized la neurons as well as muscle spindle and Golgi tendon organs are depleted, and are causative for sensory ataxia. Thus, the proprioceptive Ia neurons would play a role in pathogenesis of sensory ataxia in human sensory ataxic neuropathies, but the significance of dorsal column involvement in human sensory ataxia is still needed to evaluate.
Sandstrom, Matthew M.
This is the final report for a grant-funded project to financially assist and otherwise provide support to projects that increase E85 infrastructure in Michigan at retail fueling locations. Over the two-year project timeframe, nine E85 and/or flex-fuel pumps were installed around the State of Michigan at locations currently lacking E85 infrastructure. A total of five stations installed the nine pumps, all providing cost share toward the project. By using cost sharing by station partners, the $200,000 provided by the Department of Energy facilitated a total project worth $746,332.85. This project was completed over a two-year timetable (eight quarters). The first quarter of the project focused on project outreach to station owners about the incentive on the installation and/or conversion of E85 compatible fueling equipment including fueling pumps, tanks, and all necessary electrical and plumbing connections. Utilizing Clean Energy Coalition (CEC) extensive knowledge of gasoline/ethanol infrastructure throughout Michigan, CEC strategically placed these pumps in locations to strengthen the broad availability of E85 in Michigan. During the first and second quarters, CEC staff approved projects for funding and secured contracts with station owners; the second through eighth quarters were spent working with fueling station owners to complete projects; the third through eighth quarters included time spent promoting projects; and beginning in the second quarter and running for the duration of the project was spent performing project reporting and evaluation to the US DOE. A total of 9 pumps were installed (four in Elkton, two in Sebewaing, one in East Lansing, one in Howell, and one in Whitmore Lake). At these combined station locations, a total of 192,445 gallons of E85, 10,786 gallons of E50, and 19,159 gallons of E30 were sold in all reporting quarters for 2011. Overall, the project has successfully displaced 162,611 gallons (2,663 barrels) of petroleum, and reduced
Adams, David; Cauquil, Cecile; Lozeron, Pierre
The mechanisms of dysautonomic disturbances are varied and mostly acquired. They can result from lesions of sympathetic or parasympathetic vegetative fibers located in the peripheral contingent, or in the somatic contingent by demyelination or axonal loss; or more rarely by cellular bodies in the sympathetic or parasympathetic ganglia. Several chronic peripheral neuropathies can be associated with dysautonomia. Only some causes need to be known because they can be clinically significant. Dysautonomia may be seen during chronic acquired neuropathies but also acute or subacute ones. The most frequent cause in the world is the dysautonomia of the diabetes; it affects all the systems; the cardiovascular dysfunction has an impact on the prognosis for survival when it is severe. Hereditary autonomic neuropathies are rare; they can declare themselves very early during the Riley-Day syndrome or very late during amyloid polyneuropathies due to transthyretin gene mutation. The diagnosis can be confirmed by molecular biology. The dysautonomia is frequent and often severe. These neuropathies justify symptomatic treatment to improve quality of life. For some of them, a specific treatment can be proposed to treat the causal affection to try to stop the progression of the disease.
Autonomic neuropathy is a common complication in long-term diabetes, about 30% of the patients showing measurable signs of autonomic dysfunction after 10 years duration of disease. The diagnosis is often difficult to establish because clinical symptoms generally occur late in the course...
目的：对比不同方法筛查糖尿病周围神经病变的效用，评价不同筛查方法优劣，建立一种最佳的筛查策略。方法2013年10月～2015年10月，筛选患者100例，50例DPN纳入病例组，50例正常者纳入对照组，开展DPN相关检查，对比相关指标。结果病例组疼痛、足部检查、尼龙丝检查左、尼龙丝检查右、VPT检查左、VPT检查右高于对照组，差异有统计学意义（P＜0.05）；疼痛最佳截断点3.5、足部检查最佳截断点0.25、尼龙丝检查左1.5、尼龙丝检查右2.5、VPT左13.5、VPT右17.5，以此作为诊断分界值，敏感度最高为PVT右，特异度最高为疼痛，符合率最高为尼龙丝检查。结论重点关注VPT右与疼痛双阳性者，双阴性则基本排除病变可能，若条件不足，也可以尼龙丝检查替代PVT检查。%Objective To compare different methods of screening for diabetic peripheral neuropathy (DPN) utility, evaluate different screening methods, and establish a best screening strategy. Methods From October 2013 to October 2015, screening in 100 cases of patients, 50 patients with DPN included in the case group, 50 cases of normal people were included in the control group, to carry out inspection of DPN and comparison of relevant indicators.Results Cases of pain, foot examination, nylon wire check left, nylon wire check right, VPT left, VPT right higher than control group, the difference is statistically significant (P<0.05), Cut-off point of pain 3.5, foot to check the optimal cut-off point of 0.25, monoiflament left 1.5, 2.5 monoiflament examination right, left of the VPT 13.5, VPT right 17.5, serve as the cut-off value, sensitivity highest for PVT right, specificity of highest for pain, in line with the rate was the highest in nylon yarn inspect left. Conclusion It should focus on VPT right and double positive for pain, double negative is basic pathological changes may, if the condition is not enough, also can
Vallat, Jean-Michel; Tazir, Mériem; Calvo, Judith; Funalot, Benoît
Currently more than 30 genes are known to be responsible for genetically determined neuropathies. Charcot-Marie-Tooth (CMT) disease is the most frequent of these hereditary neuropathies, with a prevalence of 4.7 to 36 per 100 000. In its demyelinating forms (CMT1), approximately 70% of cases are associated with a duplication of the PMP22gene. In its axonal forms (CMT2), 10-20% of the cases may be associated with a mutation of the MFN2gene. For North African patients with recessive transmission, a mutation of the LMNA gene must be sought. It is essential to stress the great variability of the phenotype--clinical, electrophysiological, and histologic--between and within families. A detailed analysis of these criteria, together with consideration of ethnic origin, may guide the search for the causal mutation. Whether the case involves certainly hereditary transmission or a sporadic form, it is desirable to be able to examine the maximum number of the patient's kin, both clinically and electrophysiologically. The forms with recessive transmission usually have a very early onset and are more serious than the dominant forms. The early- and very early-onset forms of CMT are increasingly better distinguished: congenital hypomyelination neuropathy (mutations of PMP22, MPZ or EGR2), or more axonal forms, including SMARD1 (Spinal muscle atrophy with respiratory distress; mutations of IGHMBP2) and EOHMSN (Early-onset hereditary motor and sensory neuropathy; mutations of MFN2). The prevention of cutaneous (ulcerations), bone, and amputation complications is very important in patients with hereditary sensory and autonomic neuropathies, because of the severity of the sensory disorders.
Axelrod, Felicia B; Hilz, Max J
Inherited autonomic neuropathies are a rare group of disorders associated with sensory dysfunction. As a group they are termed the "hereditary sensory and autonomic neuropathies" (HSAN). Classification of the various autonomic and sensory disorders is ongoing. In addition to the numerical classification of four distinct forms proposed by Dyck and Ohta (1975), additional entities have been described. The best known and most intensively studied of the HSANs are familial dysautonomia (Riley-Day syndrome or HSAN type III) and congenital insensitivity to pain with anhidrosis (HSAN type IV). Diagnosis of the HSANs depends primarily on clinical examinations and specific sensory and autonomic assessments. Pathologic examinations are helpful in confirming the diagnosis and in differentiating between the different disorders. In recent years identification of specific genetic mutations for some disorders has aided diagnosis. Replacement or definitive therapies are not available for any of the disorders so that treatment remains supportive and directed toward specific symptoms.
Full Text Available Primary systemic vasculitis in pre-capillary arteries is associated with peripheral neuropathy. In some types of systematic vasculitis about 60 % of patients have peripheral nervous system (PNS involvement. In vasculitic peripheral neuropathies (VPN a necrotizing and inflammatory process leads to narrowing of vasa nervorum lumen and eventually the appearance of ischemic lesions in peripheral nerves. Some features might be suggestive of VPN, like: axonal nerve degeneration, wallerian-like degeneration, and diameter irregularity of nerve. Peripheral nervous system (PNS destruction during systemic vasculitides should be considered, due to its frequency and early occurrence in vasculitis progression. The first line treatment of non systematic VPNs is corticosteroid agents, but these drugs might worsen the VPNs or systemic vasculitis.
Yu-Wai-Man, P; Griffiths, P G; Hudson, G; Chinnery, P F
Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (DOA) are the two most common inherited optic neuropathies and they result in significant visual morbidity among young adults. Both disorders are the result of mitochondrial dysfunction: LHON from primary mitochondrial DNA (mtDNA) mutations affecting the respiratory chain complexes; and the majority of DOA families have mutations in the OPA1 gene, which codes for an inner mitochondrial membrane protein critical for mtDNA maintenance and oxidative phosphorylation. Additional genetic and environmental factors modulate the penetrance of LHON, and the same is likely to be the case for DOA which has a markedly variable clinical phenotype. The selective vulnerability of retinal ganglion cells (RGCs) is a key pathological feature and understanding the fundamental mechanisms that underlie RGC loss in these disorders is a prerequisite for the development of effective therapeutic strategies which are currently limited. PMID:19001017
Neuropathy is the most common and debilitating complication of diabetes and results in pain, decreased motility, and amputation. Diabetic neuropathy encompasses a variety of forms whose impact ranges from discomfort to death. Hyperglycemia induces oxidative stress in diabetic neurons and results in activation of multiple biochemical pathways. These activated pathways are a major source of damage and are potential therapeutic targets in diabetic neuropathy. Though therapies are available to al...
In diabetic patients with autonomic neuropathy plasma noradrenaline concentration, used as an index of sympathetic nervous activity, is low. This decrease is, however, only found in patients with a long duration of diabetes with clinically severe autonomic neuropathy. This apparent insensitivity...... of plasma catecholamine measurements is not due to changes in the clearance of catecholamines in diabetic autonomic neuropathy. The physiological responses to infused adrenaline and to noradrenaline are enhanced, for noradrenaline mainly cardiovascular responses. Adrenoceptors (alpha and beta adrenoceptors...
Full Text Available Painful peripheral neuropathy (PPN is characterized by neuropathic pain (NP, which is accompanied by dysfunction of motor, sensory and autonomic nervous system. It always involves small nerve fibers, including A δ and C fibers. PPN can be classified into two types according to etiology: hereditary and acquired. Pain of PPN can manifest as spontaneous pain and stimulus-evoked pain (allodynia, hyperalgesia and hyperpathia. The manifestation of typical cases is length-dependent, which firstly involves the feet, and then progresses proximally and to the hands, presenting a glove-stock pattern. PPN can be either an isolated disease entity or part of other diseases. The former indicates idiopathic small fiber neuropathy (SFN, while the latter contains various diseases involving peripheral nerve fibers, including systemic diseases such as diabetes mellitus and peripheral neuropathy with other causes. The accessory examinations of PPN include quantitative sensory testing (QST, intraepidermal nerve fiber density (IENFD, sympathetic skin response (SSR, etc. Among them, IENFD is the "golden standard" for SFN. The major therapeutic methods are to control primary diseases and relieve pain. Medications alleviating neuropathic pain consist of carbamazepine, pregabalin, gabapentin and amitriptyline, etc.
Hereditary neuropathies are the most common inherited neuromuscular diseases. Charcot-Marie-Tooth (CMT) disease represents the most common form with an average prevalence ranging from 1/2500 to 1/1200, depending on the studies. To date and with the advances of the latest generation sequencing, more than 80 genes have been identified. Although the common clinical phenotype comprises a progressive distal muscle weakness and sensory loss, foot deformities and decreased or absent tendon reflexes, clinical and electrophysiological phenotypes exhibit great variability. Moreover, atypical phenotypes are arising, overlapping with spastic paraplegia, hereditary sensory neuropathies or amyotrophic lateral sclerosis. The causative genes are involved in various biological processes such as myelin development and maintenance, biosynthesis and degradation of proteins, neuronal structural maintenance, axonal transport, endocytosis, membrane dynamics, ion-channel function and the mitochondrial network. An accurate genetic diagnosis is important for appropriate genetic counselling and treatment options. Therapeutic advances, particularly small interfering RNA therapy, are encouraging in hereditary transthyretin amyloid neuropathy. Copyright Â© 2016 Elsevier Masson SAS. All rights reserved.
Vilholm, Ole Jakob; Christensen, Alex Alban; Zedan, Ahmed;
Peripheral neuropathy can be caused by medication, and various descriptions have been applied for this condition. In this MiniReview, the term 'drug-induced peripheral neuropathy' (DIPN) is used with the suggested definition: Damage to nerves of the peripheral nervous system caused by a chemical...... substance used in the treatment, cure, prevention or diagnosis of a disease. Optic neuropathy is included in this definition. A distinction between DIPN and other aetiologies of peripheral neuropathy is often quite difficult and thus, the aim of this MiniReview is to discuss the major agents associated...
Diabetes is the leading cause of neuropathy worldwide and, due to the epidemic progression of the affection, prevalence of diabetic neuropathies will increase in the near future. Beside the typical diabetic neuropathy pattern and the common entrapment neuropathies, several unusual clinical forms have been described with either a symmetrical or an asymmetrical pattern. Treatment-induced neuropathy is an acute sensory affection most commonly related to acute glycemic control. Pain is debilitating and associated with vegetative dysfunction. Prevention is important, as resolution is often incomplete. Several patterns or asymmetrical neuropathies of inflammatory and ischemic origin were described long ago in the lower limb. They are debilitating, most often painful and require steroid treatment. Other patterns affecting the thoracolumbar region or the upper limbs or involving a painless motor deficit must be identified as specific treatments are sometimes needed. An association between diabetes and chronic inflammatory demyelinating polyneuropathy has not been demonstrated but diagnosis may be suggested due to the misleading low conduction velocities seen in classical diabetic neuropathy. Like any other patient, the diabetic patient may present a neuropathy unrelated to diabetes. To facilitate patient care, neurologists should be aware of such clinical entities. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
Nucci, Carlo; Martucci, Alessio; Mancino, Raffaele; Cerulli, Luciano
The purpose of this article is to describe a case of open-angle glaucoma progression associated with Leber's hereditary optic neuropathy. Single case analysis method is used. A 53-year-old woman with a previous diagnosis of glaucoma presented with progressive visual field loss. Complete ophthalmological examination and blood tests were negative for other concomitant diseases. Genetic counseling revealed mitochondrial DNA mutation compatible with the diagnosis of Leber's hereditary optic neuropathy. In conclusion, the case describes the concomitant occurrence of open-angle glaucoma and Leber's optic neuropathy. We hypothesize that the two diseases may have a cumulative effect on oxidative stress and retinal ganglion cell death with the consequent rapid progression of visual impairment. Screening for mitochondrial DNA mutations may be requested in patients with glaucoma who, despite pharmacologically controlled intraocular pressure, show rapid progression of the disease.
Entrapment neuropathy is not uncommon, and surgical treatment is followed by favorite result. Therefore, to obtain an accurate diagnosis based on precise knowledge of the peripheral nervous system is very important. The most popular and useful symptoms and signs of the entrapment neuropathy is paresthesia, dysesthesia and Tinel's like sign at the lesion site. Nerve conduction study is also valuable for the accurate diagnosis. For the last 30 years, the author operated on 1,399 lesions of entrapment neuropathy. They consist of 877 carpal tunnel syndrome (63%), 284 tarsal tunnel syndrome (20%), 135 ulnar neuropathy at the elbow (10%), 53 piriformis syndrome (4%), 15 thoracic outlet syndrome (1%), and others. From the pathophysiological point to view, except for the carpal tunnel syndrome, several locations and factors come into play producing the entrapment of the nerve. The author would like to stress that the entrapment neuropathy is not severe disease, though, it strongly insult the patient's quality of life.
Lee-Kubli, Corinne A; Calcutt, Nigel A
Painful neuropathy, like the other complications of diabetes, is a growing healthcare concern. Unfortunately, current treatments are of variable efficacy and do not target underlying pathogenic mechanisms, in part because these mechanisms are not well defined. Rat and mouse models of type 1 diabetes are frequently used to study diabetic neuropathy, with rats in particular being consistently reported to show allodynia and hyperalgesia. Models of type 2 diabetes are being used with increasing frequency, but the current literature on the progression of indices of neuropathic pain is variable and relatively few therapeutics have yet been developed in these models. While evidence for spontaneous pain in rodent models is sparse, measures of evoked mechanical, thermal and chemical pain can provide insight into the pathogenesis of the condition. The stocking and glove distribution of pain tantalizingly suggests that the generator site of neuropathic pain is found within the peripheral nervous system. However, emerging evidence demonstrates that amplification in the spinal cord, via spinal disinhibition and neuroinflammation, and also in the brain, via enhanced thalamic activity or decreased cortical inhibition, likely contribute to the pathogenesis of painful diabetic neuropathy. Several potential therapeutic strategies have emerged from preclinical studies, including prophylactic treatments that intervene against underlying mechanisms of disease, treatments that prevent gains of nociceptive function, treatments that suppress enhancements of nociceptive function, and treatments that impede normal nociceptive mechanisms. Ongoing challenges include unraveling the complexity of underlying pathogenic mechanisms, addressing the potential disconnect between the perceived location of pain and the actual pain generator and amplifier sites, and finding ways to identify which mechanisms operate in specific patients to allow rational and individualized choice of targeted therapies.
Nagashima, T.; Miyamoto, K.; Beppu, H.; Hirose, K.; Yamada, K. (Tokyo Metropolitan Neurological Hospital (Japan))
A case of cervical plexus neuropathy was reported in association with chronic radio-dermatitis, myxedema with thyroid adenoma and epiglottic tumor. A 38-year-old man has noticed muscle weakness and wasting of the right shoulder girdle since age 33. A detailed history taking revealed a previous irradiation to the neck because of the cervical lymphadenopathy at age 10 (X-ray 3,000 rads), keroid skin change at age 19, obesity and edema since 26, and hoarseness at 34. Laryngoscopic examination revealed a tumor on the right vocal cord, diagnosed as benign papilloma by histological study. In addition, there were chronic radio-dermatitis around the neck, primary hypothyroidism with a benign functioning adenoma on the right lobe of the thyroid, the right phrenic nerve palsy and the right recurrent nerve palsy. All these lesions were considered to be the late sequellae of radiation to the neck in childhood. Other neurological signs were weakness and amyotrophy of the right shoulder girdle with patchy sensory loss, and areflexia of the right arm. Gross power was fairly well preserved in the right hand. EMG showed neurogenic changes in the tested muscles, suggesting a peripheral nerve lesion. Nerve conduction velocities were normal. No abnormal findings were revealed by myelography and spinal CT. The neurological findings of the patient were compatible with the diagnosis of middle cervical plexus palsy apparently due to late radiation effect. In the literature eight cases of post-radiation neuropathy with a long latency have been reported. The present case with the longest latency after the radiation should be included in the series of the reported cases of ''delayed radiation neuropathy.'' (author).
In 2012, interest remains high in the field of dysimmune neuropathies, chiefly concerning Guillain-Barré syndrome (GBS). The pathophysiological mechanisms are now better known but electrophysiological criteria should be updated. The risk of GBS in H1N1 vaccination is now well evaluated. Nerve ultrasonography provides new prospects for diagnosis and follow-up of dysimmune neuropathies but cannot substitute for electrophysiology. This paper aims to present some noteworthy articles published in 2012 in the field of dysimmune neuropathies. Copyright © 2013 Elsevier Masson SAS. All rights reserved.
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Newman, Nancy J
The hereditary optic neuropathies are inherited disorders in which optic nerve dysfunction is a prominent feature in the phenotypic expression of disease. Optic neuropathy may be primarily an isolated finding, such as in Leber hereditary optic neuropathy and dominant optic atrophy, or part of a multisystem disorder. The pathophysiological mechanisms underlying the hereditary optic neuropathies involve mitochondrial dysfunction owing to mutations in mitochondrial or nuclear DNA that encodes proteins essential to mitochondrial function. Effective treatments are limited, and current management includes therapies directed at enhancing mitochondrial function and preventing oxidative damage, as well as genetic counselling, and supportive and symptomatic measures. New therapies, including gene therapy, are emerging via animal models and human clinical trials. Leber hereditary optic neuropathy, in particular, provides a unique model for testing promising treatments owing to its characteristic sequential bilateral involvement and the accessibility of target tissue within the eye. Lessons learned from treatment of the hereditary optic neuropathies may have therapeutic implications for other disorders of presumed mitochondrial dysfunction. In this Review, the natural history of the common inherited optic neuropathies, the presumed pathogenesis of several of these disorders, and the literature to date regarding potential therapies are summarized.
Full Text Available Peripheral neuropathy refers to disorders of the peripheral nervous system. They have numerous causes and diverse presentations; hence, a systematic and logical approach is needed for cost-effective diagnosis, especially of treatable neuropathies. A detailed history of symptoms, family and occupational history should be obtained. General and systemic examinations provide valuable clues. Neurological examinations investigating sensory, motor and autonomic signs help to define the topography and nature of neuropathy. Large fiber neuropathy manifests with the loss of joint position and vibration sense and sensory ataxia, whereas small fiber neuropathy manifests with the impairment of pain, temperature and autonomic functions. Electrodiagnostic (EDx tests include sensory, motor nerve conduction, F response, H reflex and needle electromyography (EMG. EDx helps in documenting the extent of sensory motor deficits, categorizing demyelinating (prolonged terminal latency, slowing of nerve conduction velocity, dispersion and conduction block and axonal (marginal slowing of nerve conduction and small compound muscle or sensory action potential and dennervation on EMG. Uniform demyelinating features are suggestive of hereditary demyelination, whereas difference between nerves and segments of the same nerve favor acquired demyelination. Finally, neuropathy is classified into mononeuropathy commonly due to entrapment or trauma; mononeuropathy multiplex commonly due to leprosy and vasculitis; and polyneuropathy due to systemic, metabolic or toxic etiology. Laboratory investigations are carried out as indicated and specialized tests such as biochemical, immunological, genetic studies, cerebrospinal fluid (CSF examination and nerve biopsy are carried out in selected patients. Approximately 20% patients with neuropathy remain undiagnosed but the prognosis is not bad in them.
Full Text Available Si-Wei You,1 Ming-Mei Wu,2 Fang Kuang,2 Kin-Sang Cho,3 Kwok-Fai So4,5 1Department of Ophthalmology, Xijing Hospital, 2Institute of Neurosciences, The Fourth Military Medical University, Xi’an, China; 3Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA; 4GHM Institute of CNS Regeneration, Key Laboratory of Brain Function and Diseases, Jinan University, Guangzhou, 5Department of Ophthalmology, The State Key laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong SAR, China Abstract: Optic neuropathy refers to disorders involving the optic nerve (ON. Any damage to ON or ON-deriving neurons, the retinal ganglion cells (RGCs, may lead to the breakdown of the optical signal transmission from the eye to the brain, thus resulting in a partial or complete vision loss. The causes of optic neuropathy include trauma, ischemia, inflammation, compression, infiltration, and mitochondrial damages. ON injuries include primary and secondary injuries. During these injury phases, various factors orchestrate injured axons to die back and become unable to regenerate, and these factors could be divided into two categories: extrinsic and intrinsic. Extrinsic inhibitory factors refer to the environmental conditions that influence the regeneration of injured axons. The presence of myelin inhibitors and glial scar, lack of neurotrophic factors, and inflammation mediated by injury are regarded as these extrinsic factors. Extrinsic factors need to trigger the intracellular signals to exert inhibitory effect. Proper regulation of these intracellular signals has been shown to be beneficial to ON regeneration. Intrinsic factors of RGCs are the pivotal reasons that inhibit ON regeneration and are closely linked with extrinsic factors. Intracellular cyclic adenosine monophosphate (cAMP and calcium levels affect axon guidance and growth cone response to guidance molecules
Maliheh Mazaher Yazdi
Full Text Available Background and Aim: Auditory neuropathy is an hearing disorder in which peripheral hearing is normal, but the eighth nerve and brainstem are abnormal. By clinical definition, patient with this disorder have normal OAE, but exhibit an absent or severely abnormal ABR. Auditory neuropathy was first reported in the late 1970s as different methods could identify discrepancy between absent ABR and present hearing threshold. Speech understanding difficulties are worse than can be predicted from other tests of hearing function. Auditory neuropathy may also affect vestibular function. Case Report: This article presents electrophysiological and behavioral data from a case of auditory neuropathy in a child with normal hearing after bilirubinemia in a 5 years follow-up. Audiological findings demonstrate remarkable changes after multidisciplinary rehabilitation. Conclusion: auditory neuropathy may involve damage to the inner hair cells-specialized sensory cells in the inner ear that transmit information about sound through the nervous system to the brain. Other causes may include faulty connections between the inner hair cells and the nerve leading from the inner ear to the brain or damage to the nerve itself. People with auditory neuropathy have OAEs response but absent ABR and hearing loss threshold that can be permanent, get worse or get better.
Leo-Kottler, B; Wissinger, B
Leber's hereditary optic neuropathy (LHON) is a rare disease primarily affecting the retinal ganglion cells. In most cases patients with LHON develop permanent visual loss with a large central scotoma in the visual field of both eyes. The optic disc becomes partially or completely pale. At the onset of the disease many patients are considered to suffer from an optic neuritis and are treated under the diagnostic and therapeutic regimen of optic neuritis. LHON is mostly only considered when high dose cortisone therapy fails to be effective or the second eye is affected. Thereafter, molecular genetic analysis will prove LHON in these cases. Detailed anamnesis including pedigree analysis in combination with observance of the peripapillary microangiopathic alterations at the fundus will help to speed up the diagnosis of LHON, but even after exact clinical and molecular genetic diagnosis of LHON some aspects of the disease still remain a mystery today.
Baloh, Robert H
Peripheral neuropathy is perhaps the archetypal disease of axonal degeneration, characteristically involving degeneration of the longest axons in the body. Evidence from both inherited and acquired forms of peripheral neuropathy strongly supports that the primary pathology is in the axons themselves and points to disruption of axonal transport as an important disease mechanism. Recent studies in human genetics have further identified abnormalities in mitochondrial dynamics--the fusion, fission, and movement of mitochondria--as a player in the pathogenesis of inherited peripheral neuropathy. This review provides an update on the mechanisms of mitochondrial trafficking in axons and the emerging relationship between the disruption of mitochondrial dynamics and axonal degeneration. Evidence suggests mitochondria are a "critical cargo" whose transport is necessary for proper axonal and synaptic function. Importantly, understanding the regulation of mitochondrial movement and the consequences of decreased axonal mitochondrial function may define new paths for therapeutic agents in peripheral neuropathy and other neurodegenerative diseases.
This thesis focuses on the efficacy of existing and alternative treatments in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) and explores predictors of treatment response in patients with CIDP treated with corticosteroids. The efficacy of intra
Bates, D. K.; Ponter, A. B.
Discusses factors leading to the development of a four-year industrial chemistry program at Michigan Technological University and provides details of its structure. Includes brief descriptions of courses required in industrial chemistry but not in the traditional chemistry program and list of optional courses. (JN)
Vulnerable children in Michigan face intersecting disparities, with race, class and geographic location often combining to limit access to health, education and economic security. Addressing this reality requires reliable and comprehensive data that can guide thoughtful action within communities and among institutions alike. To this end, the W. K.…
Moffett, James W.
This laboratory located about 40 miles west of Detroit, near the intersection of highways I-94 and US-23, can be reached by bus, railroad, or via commercial airlines to Detroit Willow Run or Metropolitan airports. Field biological stations are located in Wisconsin at Ashland; in Ohio at Sandusky; and in Michigan at Ludington, Marquette, Millersburg, and Northville.
Michigan has more than 11,000 inland lakes, that provide countless recreational opportunities and are an important resource that makes tourism and recreation a $15-billion-dollar per-year industry in the State (Stynes, 2002). Knowledge of the water-quality characteristics of inland lakes is essential for the current and future management of these resources.Historically the U. S. Geological Survey (USGS) and the Michigan Department of Environmental Quality (MDEQ) jointly have monitored water quality in Michigan's lakes and rivers. During the 1990's, however, funding for surface-water-quality monitoring was reduced greatly. In 1998, the citizens of Michigan passed the Clean Michigan Initiative to clean up, protect, and enhance Michigan's environmental infrastructure. Because of expanding water-quality-data needs, the MDEQ and the USGS jointly redesigned and implemented the Lake Water-Quality Assessment (LWQA) Monitoring Program (Michigan Department of Environmental Quality, 1997).
Namea M. Ismail
Conclusion: Patients with auditory neuropathy could also have vestibular neuropathy. Vestibular neuropathy could be classified into three groups: superior vestibular neuropathy, inferior vestibular neuropathy and superior/inferior vestibular neuropathy.
Affandi, Jacquita S; Price, Patricia; Imran, Darma; Yunihastuti, Evy; Djauzi, Samsuridjal; Cherry, Catherine L
A toxic sensory neuropathy associated with exposure to inexpensive nucleoside analogue reverse transcriptase inhibitors (NRTIs) [particularly stavudine (d4T)] causes dilemmas in the management of patients with HIV, especially in resource-poor settings. Here patients (n = 96) attending Pokdisus AIDS Clinic at the Cipto Mangunkusumo Hospital, Jakarta who had been treated with d4T were screened for symptomatic neuropathy. Clinical, demographic, and genetic factors were considered as possible neuropathy risk factors. DNA from saliva was used to examine alleles of TNFA-308, BAT1 (intron 10), TNFA-1031, IL1A+4845, and IL12B (3' UTR). The prevalence of neuropathy (symptoms and signs) was 34%. On multivariate analysis, neuropathy following d4T exposure was associated with increasing age, increasing height, and TNFA-1031*2 (model p = 0.0009). Isoniazid exposure (present in 56% of patients) was not associated with neuropathy in this cohort, where all patients had received pyridoxine coadministration. These data suggest that a simple algorithm based on patient age, height, and TNF genotype could be used to predict the individual's risk of symptomatic neuropathy prior to prescription of d4T.
Hypothyroidism: Can it cause peripheral neuropathy? Can hypothyroidism cause peripheral neuropathy and, if so, how is it treated? Answers from Todd B. Nippoldt, M.D. Hypothyroidism — a condition in which your ...
Callaghan, Brian C.; Price, Ray S.; Chen, Kevin S.; Feldman, Eva L.
Importance Peripheral neuropathy is a prevalent condition that usually warrants a thorough history and examination, but limited diagnostic evaluation. Rare localizations of peripheral neuropathy, however, often require more extensive diagnostic testing and different treatments. Objective To describe rare localizations of peripheral neuropathy, including the appropriate diagnostic evaluation and available treatments. Evidence Review References were identified from PubMed searches with an emphasis on systematic reviews and randomized clinical trials. Articles were also identified through the use of the author's own files. Search terms included common rare neuropathy localizations and their causes, as well as epidemiology, pathophysiology, diagnosis, and treatment. Findings Diffuse, non-length dependent neuropathies, multiple mononeuropathies, polyradiculopathies, plexopathies, and radiculoplexus neuropathies are rare peripheral neuropathy localizations that often require extensive diagnostic testing. Atypical neuropathy features, such as acute/subacute onset, asymmetry, and/or motor predominant signs, are frequently present. The most common diffuse, non-length dependent neuropathies are Guillain-Barre syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN), and amyotrophic lateral sclerosis (ALS). Effective disease modifying therapies exist for many diffuse, non-length dependent neuropathies including GBS, CIDP, MMN, and some paraprotein-associated demyelinating neuropathies. Vasculitic neuropathy (multiple mononeuropathy) also has efficacious treatment options, but definitive evidence of a treatment effect for IgM anti-MAG neuropathy and diabetic amyoptrophy (radiculoplexus neuropathy) is lacking. Conclusions and Relevance Recognition of rare localizations of periperhal neuropathy is essential given the implications for diagnostic testing and treatment. Electrodiagnostic studies are an important early step in the
The review concentrates on the use of clinical neurophysiology in peripheral nerve disorders covered in the present issue. It is pertinent to distinguish different types of involvement of fibers in diabetic neuropathy, including the involvement of small and large fibers, to outline the diagnostic...... criteria of inflammatory neuropathies, and to describe the spectrum of peripheral nerve pathophysiology in inherited neuropathies. Painful neuropathies represent a particular challenge to clinical neurophysiology since it is mainly small fibers, which are difficult to study, that are affected....
Greenberg Steven A
Full Text Available Abstract Background The differential diagnosis of chronic progressive multifocal asymmetric neuropathies is challenging. Vasculitic neuropathies, multifocal forms of chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathies, and asymmetric lower motor neuron disorders are important considerations. Case presentation We report a patient with an unusually long 12-year course of nonsystemic vasculitic neuropathy prior to the development of systemic manifestations. Conclusion We discuss some of the difficulties involved in the diagnosis of chronic progressive multifocal asymmetric neuropathies.
Hoeijmakers, J.G.; Bakkers, M.; Blom, E.W.; Drenth, J.P.H.; Merkies, I.S.; Faber, C.G.
Small fibre neuropathy is a neuropathy of the small non-myelinated C-fibres and myelinated Adelta-fibres. Clinically, an isolated small fibre neuropathy is distinguished by sensory and autonomic symptoms, with practically no abnormalities on neurological examination other than possible distorted pai
Pareyson, Davide; Piscosquito, Giuseppe; Moroni, Isabella; Salsano, Ettore; Zeviani, Massimo
Why is peripheral neuropathy common but mild in many mitochondrial disorders, and why is it, in some cases, the predominant or only manifestation? Although this question remains largely unanswered, recent advances in cellular and molecular biology have begun to clarify the importance of mitochondrial functioning and distribution in the peripheral nerve. Mutations in proteins involved in mitochondrial dynamics (ie, fusion and fission) frequently result in a Charcot-Marie-Tooth phenotype. Peripheral neuropathies with different phenotypic presentations occur in mitochondrial diseases associated with abnormalities in mitochondrial DNA replication and maintenance, or associated with defects in mitochondrial respiratory chain complex V. Our knowledge of mitochondrial disorders is rapidly growing as new nuclear genes are identified and new phenotypes described. Early diagnosis of mitochondrial disorders, essential to provide appropriate genetic counselling, has become crucial in a few treatable conditions. Recognising and diagnosing an underlying mitochondrial defect in patients presenting with peripheral neuropathy is therefore of paramount importance.
Rota, Eugenia; Morelli, Nicola
Neuropathy is a common complication of diabetes mellitus (DM) with a wide clinical spectrum that encompasses generalized to focal and multifocal forms. Entrapment neuropathies (EN), which are focal forms, are so frequent at any stage of the diabetic disease, that they may be considered a neurophysiological hallmark of peripheral nerve involvement in DM. Indeed, EN may be the earliest neurophysiological abnormalities in DM, particularly in the upper limbs, even in the absence of a generalized polyneuropathy, or it may be superimposed on a generalized diabetic neuropathy. This remarkable frequency of EN in diabetes is underlain by a peculiar pathophysiological background. Due to the metabolic alterations consequent to abnormal glucose metabolism, the peripheral nerves show both functional impairment and structural changes, even in the preclinical stage, making them more prone to entrapment in anatomically constrained channels. This review discusses the most common and relevant EN encountered in diabetic patient in their epidemiological, pathophysiological and diagnostic features. PMID:27660694
Eugenia; Rota[1; Nicola; Morelli[1
Neuropathy is a common complication of diabetes mellitus (DM) with a wide clinical spectrum that encompasses generalized to focal and multifocal forms. Entrapment neuropathies (EN), which are focal forms,are so frequent at any stage of the diabetic disease, that they may be considered a neurophysiological hallmark of peripheral nerve involvement in DM. Indeed, EN may be the earliest neurophysiological abnormalities in DM,particularly in the upper limbs, even in the absence of a generalized polyneuropathy, or it may be superimposed on a generalized diabetic neuropathy. This remarkable frequency of EN in diabetes is underlain by a peculiar pathophysiological background. Due to the metabolic alterations consequent to abnormal glucose metabolism, the peripheral nerves show both functional impairment and structural changes, even in the preclinical stage, making them more prone to entrapment in anatomically constrained channels. This review discusses the most common and relevant EN encountered in diabetic patient in their epidemiological, pathophysiological and diagnostic features.
Tracy, Jennifer A.; Dyck, P. James B.
Diabetes mellitus is associated with many different neuropathic syndromes, ranging from a mild sensory disturbance as can be seen in a diabetic sensorimotor polyneuropathy, to the debilitating pain and weakness of a diabetic lumbosacral radiculoplexus neuropathy. The etiology of these syndromes has been extensively studied, and may vary among metabolic, compressive, and immunological bases for the different disorders, as well as mechanisms yet to be discovered. Many of these disorders of nerve appear to be separate conditions with different underlying mechanisms, and some are directly caused by diabetes mellitus, whereas others are associated with it but not caused by hyperglycemia. We discuss a number of the more common disorders of nerve found with diabetes mellitus. We discuss the symmetrical neuropathies, particularly generalized diabetic polyneuropathy, and then the focal or asymmetrical types of diabetes-associated neuropathy. PMID:18194747
Martinez, Lourdes R.; Thornsbury, Suzanne
Michigan accounts for approximately 70 percent of the total number of tart cherry processing firms in the U.S. Changes in preferences of consumers and increasing participation of global competitors are driving down demand for traditional tart cherry products and imposing new pressures on the U.S. industry, particularly in Michigan. The objective of this report is to document main characteristics of the tart cherry processing industry in Michigan; namely, business characteristics, category of ...
Dalakas, M C
Patients treated with nucleoside analogue reverse transcriptase inhibitors (NRTIs) develop a varying degree of myopathy or neuropathy after long-term therapy. Zidovudine (AZT) causes myopathy; zalcitabine (ddC), didanosine (ddl) and lamuvidine (3TC) cause neuropathy; stavudine (d4T) and fialuridine (FIAU) cause neuropathy or myopathy and lactic acidosis. The tissue distribution of phosphorylases responsible for phosphorylation of NRTIs relates to their selective tissue toxicity. The myopathy is characterized by muscle wasting, myalgia, fatigue, weakness and elevation of CK. The neuropathy is painful, sensory and axonal. In vitro, NRTIs inhibit the gamma-DNA polymerase, responsible for replication of mtDNA, and cause mtDNA dysfunction. In vivo, patients treated with AZT, the best studied NRTI, develop a mitochondrial myopathy with mtDNA depletion, deficiency of COX (complex IV), intracellular fat accumulation, high lactate production and marked phosphocreatine depletion, as determined with in vivo MRS spectroscopy, due to impaired oxidative phosphorylation. Animals or cultured cells treated with NRTIs develop neuropathy, myopathy, or cell destruction with similar changes in the mitochondria. There is evidence that the NRTI-related neuropathy is also due to mitochondrial toxicity. The NRTIs (AZT, ddC, ddl, d4T, 3TC) contain azido groups that compete with natural thymidine triphosphate as substrates of DNA pol-gamma and terminate mtDNA synthesis. In contrast, FIAU that contains 3'-OH groups serves as an alternate substrate for thymidine triphosphate with DNA pol-gamma and is incorporated into the DNA causing permanent mtDNA dysfunction. The NRTI-induced mitochondrial dysfunction has an influence on the clinical application of these agents, especially at high doses and when combined. They have produced in humans a new category of acquired mitochondrial toxins that cause clinical manifestations resembling the genetic mitochondrial disorders.
Background Neuropathy is a rare adverse side effect of disulfiram therapy and is under-recognized. There have been few case reports documenting this side effect. Case presentation Two cases of disulfiram peripheral neuropathy are discussed. The first case is that of a 25-year-old Caucasian woman who was exposed to disulfiram therapy for a total of 8 months and developed pain and stiffness that prevented her from walking. The second case is that of a 46-year-old Caucasian woman who developed s...
赵昱; 石力; 王剑; 梁鹏飞; 王淑娟; 邱建华
目的：针对一个常染色体显性遗传性非综合征性听神经病谱系障碍家系进行已知致病基因筛查分析，了解是否存在可能致病的基因突变。方法选择本课题组收集到的一个家系4代24人作为研究对象，采集受试者外周静脉血提取基因组DNA，应用在线引物设计软件Primers进行引物设计，采用直接测序法对已知听神经病相关基因进行测序，使用DNAMan软件对序列进行比对分析。结果该家系遗传方式符合显性遗传特征，患者听力学特征符合非综合征型听神经病谱系障碍，对家系中全部患者及部分听力正常成员完成DIAPH3、OTOF、PJVK、GJB2基因外显子及线粒体DNA12S rRNA1494、1555位点的测序分析，未发现可疑致病突变。结论该家系未检测到已知相关基因致病突变，高度提示新基因突变致病的可能，有待于进一步研究。%Objective To identify possible pathogenic gene mutations in a Chinese pedigree with autosomal dominant hereditary non-syndromic auditory neuropathy spectrum disorder (ANSD) . Methods A pedigree of 4 generations (24 people ) was studied. Genomic DNA was extracted from peripheral blood. Primers were designed using a free internet primer de-sign software. Known auditory neuropathy related genes were analyzed by direct sequencing and gene sequences were ana-lyzed comparatively using the DNAMan software. Results In this pedigree, the mode of inheritance was consistent with autoso-mal dominant genetic diseases, and the characteristics of patients were in accordance with the diagnosis of auditory neuropa-thy spectrum disorder (ANSD). Direct sequencing of exons of the DIAPH3, OTOF, PJVK, GJB2 and GJB3 genes as well as the mitochondrial 12SrRNA gene in all patients and some other members with normal hearing in this pedigree showed no suspi-cious mutation. Conclusion None of the known pathogenic mutations is detected in this Chinese ANSD family, suggesting the
Zhou, Jiyin; Zhou, Shiwen
There are still no approved treatments for the prevention or of cure of diabetic neuropathy, and only symptomatic pain therapies of variable efficacy are available. Inflammation is a cardinal pathogenic mechanism of diabetic neuropathy. The relationships between inflammation and the development of diabetic neuropathy involve complex molecular networks and processes. Herein, we review the key inflammatory molecules (inflammatory cytokines, adhesion molecules, chemokines) and pathways (nuclear factor kappa B, JUN N-terminal kinase) implicated in the development and progression of diabetic neuropathy. Advances in the understanding of the roles of these key inflammatory molecules and pathways in diabetic neuropathy will facilitate the discovery of the potential of anti-inflammatory approaches for the inhibition of the development of neuropathy. Specifically, many anti-inflammatory drugs significantly inhibit the development of different aspects of diabetic neuropathy in animal models and clinical trials.
Full Text Available Ischaemic optic neuropathy is of two types: anterior (AION and posterior (PION, the first involving the optic nerve head (ONH and the second, the rest of the optic nerve. Pathogenetically AION and PION are very different diseases. AION represents an acute ischaemic disorder of the ONH supplied by the posterior ciliary artery (PCA, while PION has no specific location in the posterior part of the optic nerve and does not represent an ischaemic disorder of any definite artery. The most important step towards a logical understanding of the underlying causes, clinical features, pathogenesis and rational management of AION, is to understand the basic scientific issues involved; these are discussed in some detail. AION clinically is of two types: (1 that due to giant cell arteritis (arteritic AION: A-AION and (2 non-arteritic AION (NA-AION. NA-AION, the more common of the two, is one of the most prevalent and visually crippling diseases in the middle-aged and elderly, and is potentially bilateral. NA-AION is a multifactorial disease, with many risk factors collectively contributing to its development. Although there is no known treatment for NA-AION, reduction of risk factors is important in decreasing chances of involvement of the second eye and of further episodes. Our studies have suggested that nocturnal arterial hypotension is an important risk factor for the development and progression of NA-AION. The role of nocturnal arterial hypotension in the pathogenesis of NA-AION and management of nocturnal hypotension is discussed. Potent antihypertensive drugs, when used aggressively and/or given at bedtime, are emerging as an important risk factor for nocturnal hypotension, and there is some evidence that NA-AION may be occurring as an iatrogenic disease in some individuals. A-AION, by contrast, is an ocular emergency and requires immediate treatment with systemic corticosteroids to prevent further visual loss. The clinical parameters which help to
Parry-Jones, A R; Mitchell, J D; Gunarwardena, W J; Shaunak, S
We describe a 32-year-old woman with sequential, severe, painless visual loss in one eye and then the other, and three temporally distinct episodes of neurological disturbance suggestive of demyelination in the spinal cord. She was positive for the T14484C mutation in the mitochondrial genome, one of three common mutations causing Leber's hereditary optic neuropathy. In addition, MRI identified areas of demyelination within the periventricular white matter of the brain and within the spinal cord. The coexistence of multiple sclerosis and Leber's hereditary optic neuropathy (Harding's syndrome) is known to occur more often than would be expected by chance; therefore, screening for the Leber's mutations in multiple sclerosis patients with severe visual loss should be considered because this has important prognostic and genetic implications.
Murphy, Sinéad M
The inherited neuropathies are a clinically and genetically heterogeneous group of disorders in which there have been rapid advances in the last two decades. Molecular genetic testing is now an integral part of the evaluation of patients with inherited neuropathies. In this chapter we describe the genes responsible for the primary inherited neuropathies. We briefly discuss the clinical phenotype of each of the known inherited neuropathy subgroups, describe algorithms for molecular genetic testing of affected patients and discuss genetic counseling. The basic principles of careful phenotyping, documenting an accurate family history, and testing the available genes in an appropriate manner should identify the vast majority of individuals with CMT1 and many of those with CMT2. In this chapter we also describe the current methods of genetic testing. As advances are made in molecular genetic technologies and improvements are made in bioinformatics, it is likely that the current time-consuming methods of DNA sequencing will give way to quicker and more efficient high-throughput methods, which are briefly discussed here.
Krarup-Hansen, A; Helweg-Larsen, Susanne Elisabeth; Schmalbruch, H
Although it is well known that cisplatin causes a sensory neuropathy, the primary site of involvement is not established. The clinical symptoms localized in a stocking-glove distribution may be explained by a length dependent neuronopathy or by a distal axonopathy. To study whether the whole neur...
Groom, M; Kay, M D; Corrent, G F
Optic atrophy, which is indicative of a CNS disorder, is a rarely described manifestation of familial dysautonomia (Riley-Day syndrome). As these patients are now living longer, the prevalence of optic neuropathy also may be increasing. We present a man with familial dysautonomia and visual loss resulting from optic atrophy and visual field defect suggestive of chiasmal pathology.
Silva, Magali Aparecida Orate Menezes da; Piatto, Vânia Belintani; Maniglia, Jose Victor
Mutations in the otoferlin gene are responsible for auditory neuropathy. To investigate the prevalence of mutations in the mutations in the otoferlin gene in patients with and without auditory neuropathy. This original cross-sectional case study evaluated 16 index cases with auditory neuropathy, 13 patients with sensorineural hearing loss, and 20 normal-hearing subjects. DNA was extracted from peripheral blood leukocytes, and the mutations in the otoferlin gene sites were amplified by polymerase chain reaction/restriction fragment length polymorphism. The 16 index cases included nine (56%) females and seven (44%) males. The 13 deaf patients comprised seven (54%) males and six (46%) females. Among the 20 normal-hearing subjects, 13 (65%) were males and seven were (35%) females. Thirteen (81%) index cases had wild-type genotype (AA) and three (19%) had the heterozygous AG genotype for IVS8-2A-G (intron 8) mutation. The 5473C-G (exon 44) mutation was found in a heterozygous state (CG) in seven (44%) index cases and nine (56%) had the wild-type allele (CC). Of these mutants, two (25%) were compound heterozygotes for the mutations found in intron 8 and exon 44. All patients with sensorineural hearing loss and normal-hearing individuals did not have mutations (100%). There are differences at the molecular level in patients with and without auditory neuropathy. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.
Mitochondrial dynamics describes the continuous change in the position, size, and shape of mitochondria within cells. The morphological and functional complexity of neurons, the remarkable length of their processes, and the rapid changes in metabolic requirements arising from their intrinsic excitability render these cells particularly dependent on effective mitochondrial function and positioning. The rules that govern these changes and their functional significance are not fully understood, yet the dysfunction of mitochondrial dynamics has been implicated as a pathogenetic factor in a number of diseases, including disorders of the central and peripheral nervous systems. In recent years, a number of mutations of genes encoding proteins that play important roles in mitochondrial dynamics and function have been discovered in patients with Charcot-Marie-Tooth (CMT) disease, a hereditary peripheral neuropathy. These findings have directly linked mitochondrial pathology to the pathology of peripheral nerve and have identified certain aspects of mitochondrial dynamics as potential early events in the pathogenesis of CMT. In addition, mitochondrial dysfunction has now been implicated in the pathogenesis of noninherited neuropathies, including diabetic and inflammatory neuropathies. The role of mitochondria in peripheral nerve diseases has been mostly examined in vitro, and less so in animal models. This review examines available evidence for the role of mitochondrial dynamics in the pathogenesis of peripheral neuropathies, their relevance in human diseases, and future challenges for research in this field.
Murphy, Sinéad M; Laurá, Matilde; Reilly, Mary M
The inherited neuropathies are a clinically and genetically heterogeneous group of disorders in which there have been rapid advances in the last two decades. Molecular genetic testing is now an integral part of the evaluation of patients with inherited neuropathies. In this chapter we describe the genes responsible for the primary inherited neuropathies. We briefly discuss the clinical phenotype of each of the known inherited neuropathy subgroups, describe algorithms for molecular genetic testing of affected patients and discuss genetic counseling. The basic principles of careful phenotyping, documenting an accurate family history, and testing the available genes in an appropriate manner should identify the vast majority of individuals with CMT1 and many of those with CMT2. In this chapter we also describe the current methods of genetic testing. As advances are made in molecular genetic technologies and improvements are made in bioinformatics, it is likely that the current time-consuming methods of DNA sequencing will give way to quicker and more efficient high-throughput methods, which are briefly discussed here. Copyright © 2013 Elsevier B.V. All rights reserved.
An 18-year-old man with seizures from birth was followed in the Department of Clinical Neurological Sciences, University of Western Ontario, London, and was found to have developed a sensory neuropathy by 2 years of age following treatment with pyridoxine in doses up to 2000 mg/day.
Landrieu, Pierre; Baets, Jonathan
Hereditary neuropathies (HN) with onset in childhood are categorized according to clinical presentation, pathogenic mechanism based on electrophysiology, genetic transmission and, in selected cases, pathological findings. Especially relevant to pediatrics are the items "secondary" versus "primary" neuropathy, "syndromic versus nonsyndromic," and "period of life." Different combinations of these parameters frequently point toward specific monogenic disorders. Ruling out a neuropathy secondary to a generalized metabolic disorder remains the first concern in pediatrics. As a rule, metabolic diseases include additional, orienting symptoms or signs, and their biochemical diagnosis is based on logical algorithms. Primary, motor sensory are the most frequent HN and are dominated by demyelinating autosomal dominant (AD) forms (CMT1). Other forms include demyelinating autosomal recessive (AR) forms, axonal AD/AR forms, and forms with "intermediate" electrophysiological phenotype. Peripheral motor neuron disorders are dominated by AR SMN-linked spinal muscular atrophies. (Distal) hereditary motor neuropathies represent 40 genes with various biological functions have been found to be responsible for primary HN. Many are responsible for various phenotypes, including some without the polyneuropathic trait, and some for various types of transmission.
Magali Aparecida Orate Menezes da Silva
Full Text Available INTRODUCTION: Mutations in the otoferlin gene are responsible for auditory neuropathy. OBJECTIVE: To investigate the prevalence of mutations in the mutations in the otoferlin gene in patients with and without auditory neuropathy. METHODS: This original cross-sectional case study evaluated 16 index cases with auditory neuropathy, 13 patients with sensorineural hearing loss, and 20 normal-hearing subjects. DNA was extracted from peripheral blood leukocytes, and the mutations in the otoferlin gene sites were amplified by polymerase chain reaction/restriction fragment length polymorphism. RESULTS: The 16 index cases included nine (56% females and seven (44% males. The 13 deaf patients comprised seven (54% males and six (46% females. Among the 20 normal-hearing subjects, 13 (65% were males and seven were (35% females. Thirteen (81% index cases had wild-type genotype (AA and three (19% had the heterozygous AG genotype for IVS8-2A-G (intron 8 mutation. The 5473C-G (exon 44 mutation was found in a heterozygous state (CG in seven (44% index cases and nine (56% had the wild-type allele (CC. Of these mutants, two (25% were compound heterozygotes for the mutations found in intron 8 and exon 44. All patients with sensorineural hearing loss and normal-hearing individuals did not have mutations (100%. CONCLUSION: There are differences at the molecular level in patients with and without auditory neuropathy.
Full Text Available Abstract Hereditary sensory neuropathy type I (HSN I is a slowly progressive neurological disorder characterised by prominent predominantly distal sensory loss, autonomic disturbances, autosomal dominant inheritance, and juvenile or adulthood disease onset. The exact prevalence is unknown, but is estimated as very low. Disease onset varies between the 2nd and 5th decade of life. The main clinical feature of HSN I is the reduction of sensation sense mainly distributed to the distal parts of the upper and lower limbs. Variable distal muscle weakness and wasting, and chronic skin ulcers are characteristic. Autonomic features (usually sweating disturbances are invariably observed. Serious and common complications are spontaneous fractures, osteomyelitis and necrosis, as well as neuropathic arthropathy which may even necessitate amputations. Some patients suffer from severe pain attacks. Hypacusis or deafness, or cough and gastrooesophageal reflux have been observed in rare cases. HSN I is a genetically heterogenous condition with three loci and mutations in two genes (SPTLC1 and RAB7 identified so far. Diagnosis is based on the clinical observation and is supported by a family history. Nerve conduction studies confirm a sensory and motor neuropathy predominantly affecting the lower limbs. Radiological studies, including magnetic resonance imaging, are useful when bone infections or necrosis are suspected. Definitive diagnosis is based on the detection of mutations by direct sequencing of the SPTLC1 and RAB7 genes. Correct clinical assessment and genetic confirmation of the diagnosis are important for appropriate genetic counselling and prognosis. Differential diagnosis includes the other hereditary sensory and autonomic neuropathies (HSAN, especially HSAN II, as well as diabetic foot syndrome, alcoholic neuropathy, neuropathies caused by other neurotoxins/drugs, immune mediated neuropathy, amyloidosis, spinal cord diseases, tabes dorsalis, lepra
Frost, Poul; Johnsen, Birger; Fuglsang-Frederiksen, Anders;
Introduction: We examined whether lifestyle factors differ between patients with ulnar neuropathy confirmed by electroneurography (ENG) and those with ulnar neuropathy-like symptoms with normal ulnar nerve ENG. Methods: Among patients examined by ENG for suspected ulnar neuropathy, we identified...... 546 patients with ulnar neuropathy and 633 patients with ulnar neuropathy-like symptoms. These groups were compared with 2 separate groups of matched community referents and to each other. Questionnaire information on lifestyle was obtained. The electrophysiological severity of neuropathy was also...
Buurman, P.; Jongmans, A.G.; Nierop, K.G.J.
Soil organic matter in a chronosequence of Michigan soils (Spodic Udipsamments and precursors) was studied in thin section and by pyrolysis-gas chromatography/mass spectrometry (GC/MS). The Michigan soils were compared with a well-drained Dutch Typic Haplorthod that was studied with the same methods
Robert G. Haight
The Monarch Butterfly Project is a cooperative project between the Hiawatha National Forest of the US Forest Service and Wildlife Unlimited of Delta County, Michigan. In 1999, 58 volunteers contributed over 450 hours to monitor monarch reproduction and migation and to improve habitat for monarch butterflies near Penninsula Point, Delta County, in Michigan's upper...
Mi-Kyung Kim; Seung Hyun Kim
In Michigan, wine tourism is perceived as increasingly important concept because more and more tourists visit wineries and wine tasting rooms annually. However there have been few studies conducted concerning the economic impacts of wineries in Michigan even though the industry has been recognized as having significant economic impact potential. The primary purpose of...
W. K. Kellogg Foundation, 2012
"Native American Children in Michigan," provides a historical context for the tenuous relationship between Michigan's 12 federally recognized tribes and the state government, paying particular attention to the erosion of Native American education programs and the disproportionate number of Native children who find themselves in both the child…
Full Text Available A small group of patients with inherited neuropathy that has been shown to be caused by mutations in the BSCL2 gene. However, little information is available about the role of BSCL2 mutations in inherited neuropathies in Taiwan.Utilizing targeted sequencing, 76 patients with molecularly unassigned Charcot-Marie-Tooth disease type 2 (CMT2 and 8 with distal hereditary motor neuropathy (dHMN, who were selected from 348 unrelated patients with inherited neuropathies, were screened for mutations in the coding regions of BSCL2. Two heterozygous BSCL2 mutations, p.S90L and p.R96H, were identified, of which the p.R96H mutation is novel. The p.S90L was identified in a pedigree with CMT2 while the p.R96H was identified in a patient with apparently sporadic dHMN. In vitro studies demonstrated that the p.R96H mutation results in a remarkably low seipin expression and reduced cell viability.BSCL2 mutations account for a small number of patients with inherited neuropathies in Taiwan. The p.R96H mutation is associated with dHMN. This study expands the molecular spectrum of BSCL2 mutations and also emphasizes the pathogenic role of BSCL2 mutations in molecularly unassigned hereditary neuropathies.
Ng Wing Tin, Sophie; Ciampi de Andrade, Daniel; Goujon, Colette; Planté-Bordeneuve, Violaine; Créange, Alain; Lefaucheur, Jean-Pascal
To characterize sensory threshold alterations in peripheral neuropathies and the relationship between these alterations and the presence of pain. Seventy-four patients with length-dependent sensory axonal neuropathy were enrolled, including 38 patients with painful neuropathy (complaining of chronic, spontaneous neuropathic pain in the feet) and 36 patients with painless neuropathy. They were compared to 28 age-matched normal controls. A standardized quantitative sensory testing protocol was performed in all individuals to assess large and small fiber function at the foot. Large fibers were assessed by measuring mechanical (pressure and vibration) detection thresholds and small fibers by measuring pain and thermal detection thresholds. Between patients with neuropathy and controls, significant differences were found for mechanical and thermal detection thresholds but not for pain thresholds. Patients with painful neuropathy and those with painless neuropathy did not differ regarding mechanical or thermal thresholds, but only by a higher incidence of thermal or dynamic mechanical allodynia in case of painful neuropathy. Pain intensity correlated with the alteration of thermal detection and mechanical pain thresholds. Quantitative sensory testing can support the diagnosis of sensory neuropathy when considering detection threshold measurement. Thermal threshold deterioration was not associated with the occurrence of pain but with its intensity. There is a complex relationship between the loss or functional deficit of large and especially small sensory nerve fibers and the development of pain in peripheral neuropathy. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
Full Text Available Background: Diabetic neuropathy is an incapacitating disease that afflicts almost 50 percent of patients with diabetes. A late finding in type 1 diabetes, diabetic neuropathy can be an early finding in non insulin-dependent diabetes. Diabetic neuropathies are divided primarily into two groups, sensorimotor and autonomic. Patients may acquire only one type of diabetic neuropathy or may present with combinations of neuropathies, such as autonomic neuropathy or distal symmetric polyneuropathy, the latter of which the most common form. Motor deficits, orthostatic hypotension, silent cardiac ischemia, hyperhidrosis, vasomotor instability, gastroparesis, bladder dysfunction, and sexual dysfunction can also result from diabetic neuropathy. Strict control of blood sugar, combined with proper daily foot care, is essential to avoid the complications of this disorder. With the potential to afflict any part of the nervous system, diabetic neuropathy should be suspected in all patients with type 2 diabetes as well as patients who have had type 1 diabetes for over five years. Although some patients with diabetic neuropathy notice few symptoms, upon physical examination mild to moderately severe sensory loss may be noted by the physician. Idiopathic neuropathy has been known to precede the onset of type 2 diabetes.
Baets, Jonathan; Deconinck, Tine; De Vriendt, Els; Zimoń, Magdalena; Yperzeele, Laetitia; Van Hoorenbeeck, Kim; Peeters, Kristien; Spiegel, Ronen; Parman, Yesim; Ceulemans, Berten; Van Bogaert, Patrick; Pou-Serradell, Adolf; Bernert, Günther; Dinopoulos, Argirios; Auer-Grumbach, Michaela; Sallinen, Satu-Leena; Fabrizi, Gian Maria; Pauly, Fernand; Van den Bergh, Peter; Bilir, Birdal; Battaloglu, Esra; Madrid, Ricardo E; Kabzińska, Dagmara; Kochanski, Andrzej; Topaloglu, Haluk; Miller, Geoffrey; Jordanova, Albena; Timmerman, Vincent; De Jonghe, Peter
Early onset hereditary motor and sensory neuropathies are rare disorders encompassing congenital hypomyelinating neuropathy with disease onset in the direct post-natal period and Dejerine-Sottas neuropathy starting in infancy. The clinical spectrum, however, reaches beyond the boundaries of these two historically defined disease entities. De novo dominant mutations in PMP22, MPZ and EGR2 are known to be a typical cause of very early onset hereditary neuropathies. In addition, mutations in several other dominant and recessive genes for Charcot-Marie-Tooth disease may lead to similar phenotypes. To estimate mutation frequencies and to gain detailed insights into the genetic and phenotypic heterogeneity of early onset hereditary neuropathies, we selected a heterogeneous cohort of 77 unrelated patients who presented with symptoms of peripheral neuropathy within the first year of life. The majority of these patients were isolated in their family. We performed systematic mutation screening by means of direct sequencing of the coding regions of 11 genes: MFN2, PMP22, MPZ, EGR2, GDAP1, NEFL, FGD4, MTMR2, PRX, SBF2 and SH3TC2. In addition, screening for the Charcot-Marie-Tooth type 1A duplication on chromosome 17p11.2-12 was performed. In 35 patients (45%), mutations were identified. Mutations in MPZ, PMP22 and EGR2 were found most frequently in patients presenting with early hypotonia and breathing difficulties. The recessive genes FGD4, PRX, MTMR2, SBF2, SH3TC2 and GDAP1 were mutated in patients presenting with early foot deformities and variable delay in motor milestones after an uneventful neonatal period. Several patients displaying congenital foot deformities but an otherwise normal early development carried the Charcot-Marie-Tooth type 1A duplication. This study clearly illustrates the genetic heterogeneity underlying hereditary neuropathies with infantile onset.
Straussberg, R; Basel-Vanagaite, L; Kivity, S; Dabby, R; Cirak, S; Nurnberg, P; Voit, T; Mahajnah, M; Inbar, D; Saifi, GM; Lupski, [No Value; Delague, [No Value; Megarbane, A; Richter, A; Leshinsky, E; Berkovic, SF
The authors describe three siblings born to consanguineous parents with early onset ataxia, dysarthria, myoclonic, generalized tonic clonic seizures, upward gaze palsy, extensor plantar reflexes, sensory neuropathy, and normal cognition. Direct screening excluded mutations in FRDA, TDP1, and SACS ge
Faber, C.G.; Hoeijmakers, J.G.; Ahn, H.S.; Cheng, X.; Han, C.; Choi, J.S.; Estacion, M.; Lauria, G.; Vanhoutte, E.K.; Gerrits, M.M.; Dib-Hajj, S.; Drenth, J.P.H.; Waxman, S.G.; Merkies, I.S.
OBJECTIVE: Small nerve fiber neuropathy (SFN) often occurs without apparent cause, but no systematic genetic studies have been performed in patients with idiopathic SFN (I-SFN). We sought to identify a genetic basis for I-SFN by screening patients with biopsy-confirmed idiopathic SFN for mutations i
Khan, Shahnaz; Hung, Sandy Shen-Chi; Wong, Raymond Ching-Bong
The present review aims to provide an update of applications of induced pluripotent stem cells (iPSCs) for disease modeling, cell/gene therapy, and drug screening for optic neuropathies. Degeneration of retinal ganglion cells (RGCs) is a characteristic of optic neuropathies. Human iPSCs can serve as a model to investigate disease pathology and potential repair mechanisms. In recent years, significant progress has been made in generating RGCs from iPSCs. Various groups have reported the potential of iPSCs for modeling optic neuropathies, such as glaucoma. The literature also highlights the potential to use iPSC-derived cells for high-throughput drug and toxicity screening. The present review summarizes current work in the field of iPSCs in optic neuropathies. Future studies to characterize iPSC-derived RGCs in a more in-depth manner will help expand the use of iPSCs to model and treat optic neuropathic diseases. Furthermore, iPSC modeling can be used in drug development by offering a new avenue to test novel therapeutic drugs for optic neuropathies.
Milea, D; Verny, C
Hereditary optic neuropathies are a group of heterogeneous conditions affecting both optic nerves, with an autosomal dominant, autosomal recessive, X-related or mitochondrial transmission. The two most common non-syndromic hereditary optic neuropathies (Leber's hereditary optic neuropathy...
Nass, H. W.
A review is presented on activation analyses performed by the Michigan reactor. Typical determinations include: sodium deposited on gold leaf for nuclear physics experiments; cobalt and silver in high purity copper used in electron diffraction studies; sodium, manganese and chlorine in experimental reactor grade terphenyl; zirconium in an experimental tungsten - chromium alloy; argon, vanadium, manganese, chlorine, scandium, and iron in spectroscopic grade carbon rod; vanadium and aluminum in synthetically grown sapphires used for x-ray fluorescence studies; hafnium in uranyl nitrate; aluminum in silicon catalyst; vanadium in synthetic cadmium--telluride crystals used in electron spin resonance studies; and sodium and potassium in human tissue from internal organs, Analyses on oil samples and cadmium rod have also been performed. (P.C.H.)
Spallone, Vincenza; Ziegler, Dan; Freeman, Roy
Cardiovascular Autonomic Neuropathy (CAN) Subcommittee of Toronto Consensus Panel on Diabetic Neuropathy worked to update CAN guidelines, with regard to epidemiology, clinical impact, diagnosis, usefulness of CAN testing, and management. CAN is the impairment of cardiovascular autonomic control i....... Evidence on the cost-effectiveness of CAN testing is lacking. Apart from the preventive role of intensive glycaemic control in type 1 diabetes, recommendations cannot be given for most therapeutic approaches to CAN. Copyright © 2011 John Wiley & Sons, Ltd....... in the setting of diabetes after exclusion of other causes. The prevalence of confirmed CAN is around 20%, and increases up to 65% with age and diabetes duration. Established risk factors for CAN are glycaemic control in type 1 and a combination of hypertension, dyslipidemia, obesity and glycaemic control...
Full Text Available A 5 year old girl having hereditary sensory neuropathy, type II manifesting as congenital absence of pain sensation and trophic changes in the skin is reported. This child presented with presented with multiple ulcers over hands and feet since 2 years of age. The ulcers were non - healing type with serosanguineous discharge. There is abnormal gait and weakness in upper and lower limbs. On examination there are deep ulcers measuring 5x7x2cms over left feet. Fingers of both hands and feet were mutilated with loss of phalanges, sensations to fine touch, pain and temperature are decreased bilaterally below the mid arm and feet, vibration sensations were normal, proprioception could not be tested due to deformities. Sensory and motor nerve conduction studies showed evidence of sensorimotor axonal neuropathy.
Gutiérrez-Álvarez, Ángela-María; Carlos B. Moreno
The incidence of diabetic neuropathy increases with the duration of diabetes and the degree of hyperglycaemia. Pain is one of the most common and incapacitating symptoms of diabetic neuropathy and its pharmacological control is complex. The effectiveness of antidepressive agents has been described in different types of neuropathic pain, but their effectiveness, when used as analgesics in painful diabetic neuropathy, still remains controversial. Objective: To review the possible role of new-ge...
Dixit, Snehil; Maiya, Arun G; Shastry, B A
To evaluate the effect of moderate intensity aerobic exercise (40%-60% of Heart Rate Reserve (HRR)) on diabetic peripheral neuropathy. A parallel-group, randomized controlled trial was carried out in a tertiary health care setting, India. The study comprised of experimental (moderate intensity aerobic exercise and standard care) and control groups (standard care). Population with type 2 diabetes with clinical neuropathy, defined as a minimum score of seven on the Michigan Diabetic Neuropathy Score (MDNS), was randomly assigned to experimental and control groups by computer generated random number tables. RANOVA was used for data analysis (pexercises can play a valuable role to disrupt the normal progression of DPN in type 2 diabetes. Copyright © 2014 Elsevier Inc. All rights reserved.
Tracy, Jennifer A.; Dyck, P. James B.
Diabetes mellitus is associated with many different neuropathic syndromes, ranging from a mild sensory disturbance as can be seen in a diabetic sensorimotor polyneuropathy, to the debilitating pain and weakness of a diabetic lumbosacral radiculoplexus neuropathy. The etiology of these syndromes has been extensively studied, and may vary among metabolic, compressive, and immunological bases for the different disorders, as well as mechanisms yet to be discovered. Many of these disorders of nerv...
Full Text Available How to Cite This Article: Talebian A, Goudarzi RM, Mohammadzadeh M , Mirzadeh AS. Vincristine-Induced Cranial Neuropathy. Iran J Child Neurol. 2014 Winter; 8(1:66-68. Abstract Vincristine (VCR is a vinca alkaloid that is used for treatment of many malignancies. The vinca alkaloids are neurotoxic, usually causing a peripheral neuropathy, but cranial neuropathies are rare as side effects. Described here is the case of a 2.5-year-old boy, a known case of Wilms’ tumor, treated by vincristine (0/067 mg/kg/day and dactinomycin (0/045 mg/kg/day after surgery. Three weeks after treatment, he presented with bilateral ptosis. Neurological examination revealed bilateral ptosis with normal pupillary reflex and eye movement. He received 3.015 mg cumulative dose of vincristine before development of ptosis. Treatment with pyridoxine (150 mg/m2 p.o. BID and pyridostigmine (3 mg/kg p.o. BID started as neuroprotective agents, and after 7 days the problem disappeared. The treatment continued for 6 weeks and there were no signs of ptosis or a recurrence in follow up 2 months later.
Martinoli, Carlo, E-mail: firstname.lastname@example.org [Radiologia – DISC, Università di Genova, Largo Rosanna Benzi 8, I-16132 Genoa (Italy); Miguel-Perez, Maribel [Unit of Human Anatomy and Embryology, Department of Pathology and Experimental Therapy, Faculty of Medicine (C Bellvitge), University of Barcelona, Barcelona (Spain); Padua, Luca [Fondazione Don Gnocchi Onlus and Department of Neurology, Policlinico “A. Gemelli”, Università Cattolica del Sacro Cuore, Rome (Italy); Gandolfo, Nicola [IM2S – Institut Monégasque de Médecine and Chirurgie Sportive, Montecarlo (Monaco); Zicca, Anna [Radiologia – DISC, Università di Genova, Largo Rosanna Benzi 8, I-16132 Genoa (Italy); Tagliafico, Alberto [Radiologia – National Institute for Cancer Research, Genoa (Italy)
Neuropathies about the hip may be cause of chronic pain and disability. In most cases, these conditions derive from mechanical or dynamic compression of a segment of a nerve within a narrow osteofibrous tunnel, an opening in a fibrous structure, or a passageway close to a ligament or a muscle. Although the evaluation of nerve disorders primarily relies on neurological examination and electrophysiology, diagnostic imaging is currently used as a complement to help define the site and aetiology of nerve compression and exclude other disease possibly underlying the patient’ symptoms. Diagnosis of entrapment neuropathies about the hip with US and MR imaging requires an in-depth knowledge of the normal imaging anatomy and awareness of the anatomic and pathologic factors that may predispose or cause a nerve injury. Accordingly, the aim of this article is to provide a comprehensive review of hip neuropathies with an emphasis on the relevant anatomy, aetiology, clinical presentation, and their imaging appearance. The lateral femoral cutaneous neuropathy (meiralgia paresthetica), femoral neuropathy, sciatic neuropathy, obturator neuropathy, superior and inferior gluteal neuropathies and pudendal neuropathy will be discussed.
Botez, Stephan A; Herrmann, David N
The present review focuses on recent developments in diagnosis and treatment of sensory neuropathies. It does not seek to establish a comprehensive classification of sensory neuropathies, nor treatment guidelines per se. Diagnostic criteria and guidelines have been developed for distal symmetric polyneuropathies, small fiber sensory neuropathies and sensory neuronopathies. Novel diagnostic tools such as skin biopsies now allow diagnosis of small fiber sensory neuropathies. Genetic testing has defined new subtypes of mitochondrial neuropathies and inherited neuropathies with sensory involvement. Intravenous immunoglobulin and tumor necrosis factor-alpha inhibitors show promise for some dysimmune sensory neuropathies or neuronopathies. Additional options for management of neuropathic pain are emerging. Diagnostic methods for both acquired and hereditary sensory neuropathies have progressed in recent years, leading to earlier and more specific diagnoses and a better understanding of disease mechanisms. Much progress remains to be made regarding symptomatic and disease-modifying therapy for a range of sensory neuropathies, including those due to diabetes, HIV infection and from dysimmune or hereditary causes.
Full Text Available Aim: of the study was to rule out audiologic findings, related etiologies and its effect in pediatric patients having hearing deficits that are most likely due to a neuropathy of the eighth nerve. Study Design: Retrospective neo-natal hearing screening programme based. Subject and Methods: Subjects include 30 children aged from 0 yrs to 12 yrs, were tested with pure tone audiometry, behavioral observation audiometry, free-filed audiometry, speech audiometry, auditory brainstem response, and click evoked otoacoustic emissions. Results: Pure tone and free-field testing revealed 40 ears (66.67%, n = 60 with sloping type, sensorineural hearing loss, 20 ears (33.3%, n = 60 had flat configuration. Out of this 18 (6%, n = 30 subject showed bilateral similar configuration (either bilateral sloping type/ flat type of audiogram. Rest 12 (40%, n = 30 subject showed bilateral different pattern. 10 (33.3%, n = 30 children demonstrated fair to poor word discrimination scores and the other 2 (6.67%, n = 30 had fair to good word discrimination. For other rest of 18 (60%, n = 30 children speech test couldn′t be performed because of age limit and poor speech and language development. Out of 30 subjects 28 (93.3%, n = 30 showed normal distortion product Otoacoustic emissions and 2(6.67%, n = 30 subjects showed absent emissions. Conclusions: All thirty children demonstrated absent or marked abnormalities of brainstem auditory evoked potentials which suggest cochlear outer hair cell function is normal; mostly lesion is located at the eighth nerve or beyond. Generally auditory neuropathy is associated with different etiologies and it is difficult to diagnose auditory neuropathy with single audiological test; sufficient test of battery is required for complete assessment and diagnosis of auditory neuropathy
Pedersen, P B; Hogenhaven, H
A case of penicillamin-induced severe polyradiculopathy in rheumatoid arthritis is presented. The neuropathy was of demyelinating type, purely motor, proximal and clinically fully reversible when the drug ceased. In case of a progressive neuropathy, during penicillamin treatment, this adverse...
Mohapatra, Satyakam; Sahoo, Manas Ranjan; Rath, Neelmadhav
Disulfiram is widely used for aversive treatment of alcoholism. Neuropathy is one of the most severe side effects of disulfiram therapy. We report the case of a young man who developed a neuropathy following disulfiram administration, with a virtually complete recovery within 2 months.
Gilhuis, H.J.; Schelhaas, H.J.; Cruysberg, J.R.M.; Zwarts, M.J.
We report a patient with Leber hereditary optic neuropathy (G11778A mtDNA) and a severe demyelinating neuropathy, for which no other cause except his mitochondrial disorder could be found. The involvement of the peripheral nervous system of patients with LHON, in particular with a 11778 mtDNA, is di
Burakgazi, Ahmet Z; Höke, Ahmet
Common peripheral neuropathies do not usually cause diaphragmatic weakness and subsequent respiratory compromise. However, respiratory involvement is relatively common in Guillain-Barré syndrome (GBS). Experience in GBS has led to a standardized approach to manage respiratory problems in peripheral neuropathies. Diaphragmatic weakness is not common in chronic inflammatory demyelinating polyneuropathy and extremely rare in multifocal motor neuropathy. The linkage has been described between certain subtypes of Charcot-Marie-Tooth (CMT) disease such as CMT2C and CMT4B1 and diaphragmatic weakness. A correlation usually has not been found between electrophysiologic findings and clinical respiratory signs or spirometric abnormalities in peripheral neuropathies except in amplitudes of evoked phrenic nerve responses. Careful and frequent assessment of respiratory function by a qualified team of healthcare professionals and physicians is essential. Criteria established for mechanical ventilation in GBS cases may be applied to other peripheral neuropathies with respiratory compromise as necessary.
Singleton, J Robinson; Smith, A Gordon
Diabetes is associated with a variety of chronic and acute neuropathies. In this article, the authors summarize the clinical features of the most common diabetic neuropathies, focusing on those for which therapy is available or under active investigation. Distal symmetric polyneuropathy (DSP) is the most common form. Potential treatments for DSP are discussed in four broad themes: (1) medication and lifestyle therapy to improve hyperglycemia, insulin resistance, and attendant features of metabolic syndrome, including obesity and dyslipidemia; (2) pharmacologic therapy to alter neuropathy natural history aimed at rational targets from known pathophysiology; (3) symptomatic relief of neuropathic pain; and (4) treatment to prevent complications of neuropathy, including stasis ulcers and falls. The approach to the most common acute diabetic neuropathies is also reviewed. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Rossor, Alexander M; Kalmar, Bernadett; Greensmith, Linda; Reilly, Mary M
The distal hereditary motor neuropathies (dHMN) comprise a heterogeneous group of diseases that share the common feature of a length-dependent predominantly motor neuropathy. Many forms of dHMN have minor sensory abnormalities and/or a significant upper-motor-neuron component, and there is often an overlap with the axonal forms of Charcot-Marie-Tooth disease (CMT2) and with juvenile forms of amyotrophic lateral sclerosis and hereditary spastic paraplegia. Eleven causative genes and four loci have been identified with autosomal dominant, recessive and X-linked patterns of inheritance. Despite advances in the identification of novel gene mutations, 80% of patients with dHMN have a mutation in an as-yet undiscovered gene. The causative genes have implicated proteins with diverse functions such as protein misfolding (HSPB1, HSPB8, BSCL2), RNA metabolism (IGHMBP2, SETX, GARS), axonal transport (HSPB1, DYNC1H1, DCTN1) and cation-channel dysfunction (ATP7A and TRPV4) in motor-nerve disease. This review will summarise the clinical features of the different subtypes of dHMN to help focus genetic testing for the practising clinician. It will also review the neuroscience that underpins our current understanding of how these mutations lead to a motor-specific neuropathy and highlight potential therapeutic strategies. An understanding of the functional consequences of gene mutations will become increasingly important with the advent of next-generation sequencing and the need to determine the pathogenicity of large amounts of individual genetic data.
Amir Aslam; Jaipaul Singh; Satyan Rajbhandari
The prevalence of diabetes is rising globally and, as a result, its associated complications are also rising. Painful diabetic neuropathy (PDN) is a well-known complication of diabetes and the most common cause of all neuropathic pain. About one-third of all diabetes patients suffer from PDN. It has a huge effect on a person's daily life, both physically and mentally. Despite huge advances in diabetes and neurology, the exact mechanism of pain causation in PDN is still not clear. The origin o...
Azulay, J P; Pouget, J; Rihet, P; Serratrice, G
Multifocal motor neuropathy is characterized by a progressive asymetrical weakness, predominantly affecting the upper limbs with persistent conduction blocks on motor but not sensory nerves. Treatment woth prednisone and plasma exchanges have failed to demonstrate any positive effects. Some improvements have been reported with cyclophosphamide. Mainly immunoglobulin therapy has been evaluated with a beneficial response in almost 70% of the cases. These benefits obtained over periods of less than six months have recently been confirmed by a long-term evaluation of 18 patients treated by repeated infusions.
Krarup-Hansen, A; Helweg-Larsen, Susanne Elisabeth; Schmalbruch, H
Although it is well known that cisplatin causes a sensory neuropathy, the primary site of involvement is not established. The clinical symptoms localized in a stocking-glove distribution may be explained by a length dependent neuronopathy or by a distal axonopathy. To study whether the whole neuron...... of large dorsal root ganglion cells. Motor conduction studies, autonomic function and warm and cold temperature sensation remained unchanged at all doses of cisplatin treatment. The results of these studies are consistent with degeneration of large sensory neurons whereas there was no evidence of distal...
Kim, Si Yeon; Yoon, Pyeong Ho; Chung, Jin Il; Lee, Seung Ik; Kim, Dong Ik [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of)
The trigeminal nerve is the largest of the cranial nerves and has both sensory and motor functions. It can be divided into proximal (brainstem, preganglionic, gasserian ganglion, and cavernous sinus) and distal (extracranial opthalmic, maxillary, and mandibular) segments. Patients with trigeminal neuropathy present with a wide variety of symptoms, and lesions producing those symptoms may occur anywhere along the protracted course of the trigeminal nerve, from its distal facial branches to its nuclear columns in the brainstem. The purpose of this article is to illustrate the normal anatomy of the trigeminal nerve and associated various pathologic conditions. These are arranged anatomically according to their site of interaction with it.
Andersen, H; Gadeberg, P C; Brock, B
Diabetic patients with polyneuropathy develop motor dysfunction. To establish whether motor dysfunction is associated with muscular atrophy the ankle dorsal and plantar flexors of the non-dominant leg were evaluated with magnetic resonance imaging in 8 patients with symptomatic neuropathy, in 8 non...... confirmed that the atrophy predominated distally. We conclude that muscular atrophy underlies motor weakness at the ankle in diabetic patients with polyneuropathy and that the atrophy is most pronounced in distal muscles of the lower leg indicating that a length dependent neuropathic process explains...
Separate discussion of immune-mediated neuropathies from other neuropathies is justified by the serious consequences of the natural course of these diseases, like disability and sometimes even life threatening conditions. On the other hand nowadays effective treatments already exist, and with timely and correct diagnosis an appropriately chosen treatment may result in significant improvement of quality of life, occasionally even complete recovery. These are rare diseases, and the increasing number of different variants makes it more difficult to recognize them. Their diagnosis is based on the precise knowledge of clinical signs and symptoms, and it is verified by the help of neurophysiologic and laboratory, first of all CSF examinations. Description of clinical features of the classic acute immune-mediated neuropathy, characterized by ascending paresis and demyelination is followed by a summary of characteristics of newly recognized axonal, regional and functional variants. Chronic immune-mediated demyelinating polyneuropathies are not diagnosed in due number even today. This paper does not only present the classic form but it also introduces the ever increasing special variants, like distal acquired demyelinating sensory neuropathy, Lewis-Sumner syndrome, multifocal motor neuropathy and paraproteinemic neuropathies. Vasculitic neuropathies can be divided into two groups: systemic and non-systemic ones. The first sign of a vasculitic neuropathy is a progressive, painful mononeuropathy; the classic clinical presentation is the mononeuritis multiplex. It is characterized by general signs like fever, loss of weight, fatigue. In systemic vasculitis organ specific symptoms are also present. From the paraneoplastic diseases the subacute sensory neuropathy and the sensory neuronopathy are members of the immune-mediated neuropathies, being most frequently associated with small cell lung cancer.
Melli, Giorgia; Höke, Ahmet
Background Peripheral neuropathies affect many people worldwide and are caused by or associated with a wide range of conditions, both genetic and acquired. Current therapies are directed at symptomatic control because no effective regenerative treatment exists. Primary challenge is that mechanisms that lead to distal axonal degeneration, a common feature of all peripheral neuropathies, are largely unknown. Objective/Methods To address the role and specific characteristics of dorsal root ganglia (DRG) derived sensory neuron culture system as a useful model in evaluating the pathogenic mechanisms of peripheral neuropathies and examination and validation of potential therapeutic compounds. A thorough review of the recent literature was completed and select examples of the use of DRG neurons in different peripheral neuropathy models were chosen to highlight the utility of these cultures. Conclusion Many useful models of different peripheral neuropathies have been developed using DRG neuronal culture and potential therapeutic targets have been examined, but so far none of the potential therapeutic compounds have succeeded in clinical trials. In recent years, focus has changed to evaluation of axon degeneration as the primary outcome measure advocating a drug development strategy starting with phenotypic drug screening, followed by validation in primary complex co-cultures and animal models. PMID:20657751
Calpena, E; Martínez-Rubio, D; Arpa, J; García-Peñas, J J; Montaner, D; Dopazo, J; Palau, F; Espinós, C
Hereditary recurrent neuropathies are uncommon. Disorders with a known molecular basis falling within this group include hereditary neuropathy with liability to pressure palsies (HNPP) due to the deletion of the PMP22 gene or to mutations in this same gene, and hereditary neuralgic amyotrophy (HNA) caused by mutations in the SEPT9 gene. We report a three-generation family presenting a hereditary recurrent neuropathy without pathological changes in either PMP22 or SEPT9 genes. We performed a genome-wide mapping, which yielded a locus of 12.4 Mb on chromosome 21q21. The constructed haplotype fully segregated with the disease and we found significant evidence of linkage. After mutational screening of genes located within this locus, encoding for proteins and microRNAs, as well as analysis of large deletions/insertions, we identified 71 benign polymorphisms. Our findings suggest a novel genetic locus for a recurrent hereditary neuropathy of which the molecular defect remains elusive. Our results further underscore the clinical and genetic heterogeneity of this group of neuropathies.
Khanakova, N A; Sheremet, N L; Loginova, A N; Chukhrova, A L; Poliakov, A V
The article presents a review of literature on hereditary optic neuropathies: Leber mitochondrial hereditary optic neuropathy, autosomal dominant and autosomal recessive optic neuropathies, X-linked optic atrophy. Clinical and molecular genetic characteristics are covered. Isolated optic neuropathies, as well as hereditary optic disorders, being a part of a complex syndromic disease are described.
Full Text Available Diabetic autonomic neuropathy (DAN is a serious and common complication of diabetes, often overlooked and misdiagnosed. It is a systemic-wide disorder that may be asymptomatic in the early stages. The most studied and clinically important form of DAN is cardiovascular autonomic neuropathy (CAN defined as the impairment of autonomic control of the cardiovascular system in patients with diabetes after exclusion of other causes. The reported prevalence of DAN varies widely depending on inconsistent definition, different diagnostic method, different patient cohorts studied. The pathogenesis is still unclear and probably multifactorial. Once DAN becomes clinically evident, no form of therapy has been identified which can effectively stop or reverse it. Prevention strategies are based on strict glycemic control with intensive insulin treatment, multifactorial intervention and lifestyle modification including control of hypertension, dyslipidemia, stop smoking, weight loss and adequate physical exercise. The present review summarizes the latest knowledge regarding clinical presentation, epidemiology, pathogenesis and management of DAN, with some mention to childhood and adolescent population.
Huerva, V; Sánchez, M C; Ascaso, F J; Craver, L; Fernández, E
A 51-year-old woman on hemodialysis for chronic renal failure complained of visual loss in her right eye. Right optic disc edema was observed on fundus examination. An arteritic optic neuropathy was suspected. However, a first biopsy did not reveal any inflammatory cells. Two months later, the patient experienced sudden visual loss in her left eye and presented with necrotic cutaneous lesions at the distal phalanges of several fingers of the right hand. Necrotic lesions also appeared on the inner aspect of the thighs. Biopsy of the cutaneous lesions revealed calcification in the wall of a small artery. A new biopsy of the temporal artery showed large calcium deposits in the artery's tunica media. The diagnosis of optic neuropathy secondary to calciphylaxis was made. A temporal artery biopsy should be repeated if the first one is inconclusive. An early diagnosis leading to appropriate treatment may help to prevent an irreversible loss of vision in these patients. Copyright Â© 2011 Elsevier Masson SAS. All rights reserved.
Talebian, Ahmad; Goudarzi, Razieh Moazam; Mohammadzadeh, Mahdi; Mirzadeh, Azadeh Sadat
Vincristine (VCR) is a vinca alkaloid that is used for treatment of many malignancies. The vinca alkaloids are neurotoxic, usually causing a peripheral neuropathy, but cranial neuropathies are rare as side effects. Described here is the case of a 2.5-year-old boy, a known case of Wilms' tumor, treated by vincristine (0.067 mg/kg/day) and dactinomycin (0.045 mg/kg/day) after surgery. Three weeks after treatment, he presented with bilateral ptosis. Neurological examination revealed bilateral ptosis with normal pupillary reflex and eye movement. He received 3.015 mg cumulative dose of vincristine before development of ptosis. Treatment with pyridoxine (150 mg/m2 p.o. BID) and pyridostigmine (3 mg/kg p.o. BID) was started as neuroprotective agents, and after 7 days the problem disappeared. The treatment continued for 6 weeks and there were no signs of ptosis or a recurrence in follow up 2 months later.
Parman, Yeşim; Battaloğlu, Esra
Recessively transmitted predominantly motor neuropathies are rare and show a severe phenotype. They are frequently observed in populations with a high rate of consanguineous marriages. At least 15 genes and six loci have been found to be associated with autosomal recessive CMT (AR-CMT) and X-linked CMT (AR-CMTX) and also distal hereditary motor neuronopathy (AR-dHMN). These disorders are genetically heterogeneous but the clinical phenotype is relatively homogeneous. Distal muscle weakness and atrophy predominating in the lower extremities, diminished or absent deep tendon reflexes, distal sensory loss, and pes cavus are the main clinical features of this disorder with occasional cranial nerve involvement. Although genetic diagnosis of some of subtypes of AR-CMT are now available, rapid advances in the molecular genetics and cell biology show a great complexity. Animal models for the most common subtypes of human AR-CMT disease provide clues for understanding the pathogenesis of CMT and also help to reveal possible treatment strategies of inherited neuropathies. This chapter highlights the clinical features and the recent genetic and biological findings in these disorders based on the current classification.
Full Text Available How to Cite This Article: Talebian A, Goudarzi RM, Mohammadzadeh M , Mirzadeh AS. Vincristine-Induced Cranial Neuropathy. Iran J Child Neurol. 2014 Winter; 8(1:66-68. AbstractVincristine (VCR is a vinca alkaloid that is used for treatment of many malignancies.The vinca alkaloids are neurotoxic, usually causing a peripheral neuropathy, but cranial neuropathies are rare as side effects. Described here is the case of a 2.5-year-old boy, a known case of Wilms’ tumor, treated by vincristine (0/067 mg/kg/day and dactinomycin (0/045 mg/kg/day after surgery. Three weeks after treatment, he presented with bilateral ptosis.Neurological examination revealed bilateral ptosis with normal pupillary reflex and eye movement. He received 3.015 mg cumulative dose of vincristine before development of ptosis.Treatment with pyridoxine (150 mg/m2 p.o. BID and pyridostigmine (3 mg/kg p.o. BID started as neuroprotective agents, and after 7 days the problem disappeared.The treatment continued for 6 weeks and there were no signs of ptosis or a recurrence in follow up 2 months later. References:Toopchizade V, Hosseini M, et al. Electrophysiological signs of neuropathy caused by vincristine. Medical Journal of Tabriz University of Medical Sciences. 2010 Autumn;31(3; 19-25.Gursel E.S. Vincristine-Induced Unilateral Ptosis in a Child. Pediatr Neurol 2009; 41:461-463.Ngamphaiboon N, Sweeney R, Wetzler M, Wang ES. Pyridoxine treatment of vincristine-induced cranial polyneuropathy in an adult patient with acute lymphocytic leukemia: Case report and review of the literature. Leuk Res. 2010 Aug;34(8:e194-6.Lash SC, Williams CP, Marsh CS, Crithchley C, Hodgkins PR, Mackie EJ. Acute Sixth-Nerve Palsy After Vincristine Therapy. Journal of AAPOS 2004 Feb;8(1: 67-8.Bay A, Yilmaz C, Yilmaz N, Oner AF. Vincristine induced cranial polyneuropathy. Indian J Pediatr. 2006 Jun;73(6:531-3.Tuxen M K, Hansen SW. Complication of treatment, Neurotoxicity secondary to antineoplastic
Full Text Available The spectrum of chronic dysimmune neuropathies has widened well beyond chronic demyelinating polyradiculoneuropathy (CIDP. Pure motor (multifocal motor neuropathy, sensorimotor with asymmetrical involvement (multifocal acquired demylinating sensory and motor neuropathy, exclusively distal sensory (distal acquired demyelinating sensory neuropathy and very proximal sensory (chronic immune sensory polyradiculopathy constitute the variants of CIDP. Correct diagnosis of these entities is of importance in terms of initiation of appropriate therapy as well as prognostication of these patients. The rates of detection of immune-mediated neuropathies with monoclonal cell proliferation (monoclonal gammopathy of unknown significance, multiple myeloma, etc. have been facilitated as better diagnostic tools such as serum immunofixation electrophoresis are being used more often. Immune neuropathies associated with malignancies and systemic vasculitic disorders are being defined further and treated early with better understanding of the disease processes. As this field of dysimmune neuropathies will evolve in the future, some of the curious aspects of the clinical presentations and response patterns to different immunosuppressants or immunomodulators will be further elucidated. This review also discusses representative case studies.
Marmiroli, Paola; Cavaletti, Guido
Peripheral neuropathies are frequent in association with systemic diseases as well as isolated disorders. Recent advances in the therapy of specific neuropathies led to the approval of new drugs/treatments. This review selected those peripheral neuropathies where the most recent approvals were provided and revised the potential future developments in diabetic and toxic-induced neuropathies, although they do not have a currently available causal therapy in view of their epidemiological and social relevance. Data have been extracted from the most important published trials and from clinical experience. In addition, data from the Food and Drug Administration and European Medicine Agency indications on the treatment of the selected peripheral neuropathies and from recently updated international guidelines have also been included. The website of the U.S. National Institutes of Health www.clinicaltrials.gov registry has been used as the reference database for phase III clinical trials not yet published or ongoing. This review gives a general overview of the most recent advances in the treatment of amyloid, inflammatory, and paraproteinemic peripheral neuropathies. Moreover, it briefly describes the unmet medical need in disabling and frequent conditions, such as diabetic and chemotherapy-induced neuropathy, highlighting the most promising therapeutic approaches to their treatment.
Motor or motor-predominant neuropathies may arise from disease processes affecting the motor axon and/or its surrounding myelin. Lower motor neuron syndrome (LMNS) arises from a disease process affecting the spinal motor neuron itself. The term LMNS is more generally used, rather than motor neuronopathy, although both entities are clinically similar. Common features are muscle weakness (distal or proximal) with atrophy and hyporeflexia, but no sensory involvement. They can be acquired or hereditary. Immune-mediated neuropathies (multifocal motor neuropathy, motor-predominant chronic inflammatory demyelinating polyneuropathy) are important to identify, as effective treatments are available. Other acquired neuropathies, such as infectious, paraneoplastic and radiation-induced neuropathies are also well known. Focal LMNS is an amyotrophic lateral sclerosis (ALS)-mimicking syndrome especially affecting young adults. The main hereditary LMNSs in adulthood are Kennedy's disease, late-onset spinal muscular atrophy and distal hereditary motor neuropathies. Motor neuropathies and LMNS are all clinical entities that should be better known, despite being rare diseases. They can sometimes be difficult to differentially diagnose from other diseases, particularly from the more frequent ALS in its pure LMN form. Nevertheless, correct identification of these syndromes is important because their treatment and prognoses are definitely different. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
F Gökçem Yıldız
Full Text Available Objective: Hereditary neuropathy with liability to pressure palsy (HNPP needs to be differentiated from entrapment neuropathies due to differences in the treatment management. Materials and Methods: Among 5075 patients with entrapment neuropathy, we retrospectively evaluated the neurophysiologic results of 20 patients with three or more entrapments. Results: Ten patients were diagnosed as having HNPP according to their genetic or nerve biopsy results; eight (80% had bilateral Carpal tunnel syndrome, nine (90% had bilateral ulnar entrapment neuropathy, eight (80% had bilateral median and ulnar entrapment together; and three (30% had one-sided peroneal neuropathy. Conclusion: Our data suggest that analyzing the neurophysiologic studies and keeping HNPP in mind are essential to characterize underdiagnosed patients with HNPP referred for entrapment neuropathy.
Selvarajah, Dinesh; Wilkinson, Iain D; Davies, Jennifer; Gandhi, Rajiv; Tesfaye, Solomon
Diabetic neuropathy is a chronic and often disabling condition that affects a significant number of individuals with diabetes. Long considered a disease of the peripheral nervous system, there is now increasing evidence of central nervous system involvement. Recent advances in neuroimaging methods detailed in this review have led to a better understanding and refinement of how diabetic neuropathy affects the central nervous system. Recognition that diabetic neuropathy is, in part, a disease that affects the whole nervous system is resulting in a critical rethinking of this disorder, opening a new direction for further research.
Mukund R Thatte
Full Text Available Entrampment neuropathy or compression neuropathy is a fairly common problem in the upper limb. Carpal tunnel syndrome is the commonest, followed by Cubital tunnel compression or Ulnar Neuropathy at Elbow. There are rarer entities like supinator syndrome and pronator syndrome affecting the Radial and Median nerves respectively. This article seeks to review comprehensively the pathophysiology, Anatomy and treatment of these conditions in a way that is intended for the practicing Hand Surgeon as well as postgraduates in training. It is generally a rewarding exercise to treat these conditions because they generally do well after corrective surgery. Diagnostic guidelines, treatment protocols and surgical technique has been discussed.
Sonnino, Sandro; Chiricozzi, Elena; Ciampa, Maria Grazia; Mauri, Laura; Prinetti, Alessandro; Toffano, Gino; Aureli, Massimo
In peripheral neuropathies, such as sensorimotor neuropathies, motor neuron diseases, or the Guillain-Barré syndrome, serum antibodies recognizing saccharide units, portion of oligosaccharides, or oligosaccharide chains, have been found. These antibodies are called anti-glycosphingolipid (GSL) or anti-ganglioside antibodies. However, the information on the aglycone carrying the hydrophilic oligosaccharide remains elusive. The absolute and unique association of GSL to the onset, development and symptomatology of the peripheral neuropathies could be misleading. Here, we report some thoughts on the matter.
Reilly, M M; Shy, M E
The genetic neuropathies are a clinically and genetically heterogeneous group of diseases of which the most common types are Charcot-Marie-Tooth disease (CMT), the hereditary sensory and autonomic neuropathies and the distal hereditary motor neuropathies. More than 30 causative genes have been described, making an accurate genetic diagnosis increasingly possible. Although no specific therapies are yet available, research into their pathogenesis has revolutionised our understanding of the peripheral nervous system and allowed the development of rational approaches to therapy. The first therapeutic trials in CMT are currently underway. This review will suggest an approach to the diagnosis of these disorders and provide an update on new therapies.
Rota, E; Cocito, D
Electrodiagnosis of subclinical diabetic neuropathies by nerve conduction studies remains challenging. The question arises about which nerves should be tested and what the best electrodiagnostic protocol to make an early diagnosis of diabetic neuropathies would be. On the basis of our findings and other evidence, which highlighted the remarkable prevalence of electrophysiological abnormalities in nerve conduction studies of the upper limbs, often in the presence of normal lower limb conduction parameters, we suggest that both ulnar and median nerves, in their motor and sensitive component, should be the two target nerves for electrodiagnostic protocols in diabetic neuropathies.
Tey, Shelisa; Ahmad-Annuar, Azlina; Drew, Alexander P; Shahrizaila, Nortina; Nicholson, Garth A; Kennerson, Marina L
The cytoplasmic dynein heavy chain (DYNC1H1) gene has been increasingly associated with neurodegenerative disorders including axonal Charcot-Marie-Tooth disease (CMT2), intellectual disability and malformations of cortical development. In addition, evidence from mouse models (Loa, catabolite repressor-activator (Cra) and Sprawling (Swl)) has shown that mutations in Dync1h1 cause a range of neurodegenerative phenotypes with motor and sensory neuron involvement. In this current study, we examined the possible contribution of other cytoplasmic dynein subunits that bind to DYNC1H1 as a cause of inherited peripheral neuropathy. We focused on screening the cytoplasmic dynein intermediate, light intermediate and light chain genes in a cohort of families with inherited peripheral neuropathies. Nine genes were screened and ten variants were detected, but none was identified as pathogenic, indicating that cytoplasmic dynein intermediate, light intermediate and light chains are not a cause of neuropathy in our cohort.
Carlisle, E. Fred
On Feb. 6, 1961, the Board of Trustees of Michigan State University declared that MSU was "in a state of financial crisis". The development and implementation of long-range planning at Michigan State since the crisis is discussed. (MLW)
Miller, E.; Nobler, E.; Wolf, C.; Doris, E.
The solar industry in the United States is at a turning point; the cost of PV hardware has declined substantially in recent years, placing new attention on reducing the balance of system (BOS) costs of solar that now contribute to a growing percentage of installation expenses. How states address these costs through the creation of a favorable policy and regulatory environment is proving to be a critical determinant of a thriving statewide solar market. This report addresses the permitting and tax issues that may stimulate the solar market growth in Michigan. By making PV installations easier to complete through reduced BOS costs, Michigan would become a more attractive location for manufacturers and installers. As PV module costs decline and BOS costs make up a greater share of the cost of solar, action taken today on these issues will prove beneficial in the long term, providing Michigan an opportunity to establish a leadership position in the solar industry.
Obiako, O R; Ogoina, D; Abubakar, S A; Muktar, H M; Sheikh, T L; Tabi-Ajayi, E; Kehinde, J A; Iwuozo, E U; Musa, B O P
Highly active antiretroviral therapy (HAART) has been shown to reduce AIDS- defining illnesses, including neuropathies. However, it has been postulated that an increase in age -, HIV- and HAART- related neurological complications will occur as HIV-infected persons live longer. This study investigated the frequency and outcome of neuropathies in relation to CD4+ cell count and HAART status of hospitalised HIV/AIDS patients in Shika. Consecutive adult (e"15 years) non pregnant HIV- infected patients treated at Ahmadu Bello University Teaching Hospital Shika-Zaria from January 2006 to May 2013 with neuropathies were studied. Non HIV-infected patients with neurological disorders and HIV-infected patients without neuropathies were excluded. Of 5240 HIV/AIDS patients seen , 11% (566) presented with neuropathy at median CD4+ cell counts of 200 cells / ul, with yearly reduction of the frequency of patients with neuropathy from 3.9% in 2006 to 0.06% in 2013. Male: female ratio was 2:1 and respective mean years were 41.9±10.1: 45.3±17.4 (pneuropathies. However, late presentation, low CD4+ cell counts and failure of patients to start HAART early were responsible for AIDS-related mortality thus highlighting the importance of early HIV screening and treatment.
Full Text Available Many systemic antimicrobials have been implicated to cause ocular adverse effects. This is especially relevant in multidrug therapy where more than one drug can cause a similar ocular adverse effect. We describe a case of progressive loss of vision associated with linezolid therapy. A 45-year-old male patient who was on treatment with multiple second-line anti-tuberculous drugs including linezolid and ethambutol for extensively drug-resistant tuberculosis (XDR-TB presented to us with painless progressive loss of vision in both eyes. Color vision was defective and fundus examination revealed optic disc edema in both eyes. Ethambutol-induced toxic optic neuropathy was suspected and tablet ethambutol was withdrawn. Deterioration of vision occurred despite withdrawal of ethambutol. Discontinuation of linezolid resulted in marked improvement of vision. Our report emphasizes the need for monitoring of visual function in patients on long-term linezolid treatment.
Herbst, Kristina; Sander, Birgit; Lund-Andersen, Henrik
The intrinsically photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin, which is sensitive to blue light. Previous chromatic pupillometry studies have shown that the post-illumination response is considered an indicator of the melanopsin activation. The aim......-affected eyes, compared with the non-affected fellow eyes, suggesting dysfunction of the ipRGCs. Compared with the responses of the healthy controls, the blue light post-illumination pupil responses were similar in the affected eyes and increased in the fellow non-affected eyes. This suggests a possible...... of this study was to investigate the ipRGC mediated pupil response in patients with a unilateral non-arteritic anterior ischemic optic neuropathy (NAION). Consensual pupil responses during and after exposure to continuous 20 s blue (470 nm) or red (660 nm) light of high intensity (300 cd/m(2)) were recorded...
Full Text Available The prevalence of diabetes is rising globally and, as a result, its associated complications are also rising. Painful diabetic neuropathy (PDN is a well-known complication of diabetes and the most common cause of all neuropathic pain. About one-third of all diabetes patients suffer from PDN. It has a huge effect on a person’s daily life, both physically and mentally. Despite huge advances in diabetes and neurology, the exact mechanism of pain causation in PDN is still not clear. The origin of pain could be in the peripheral nerves of the central nervous system. In this review, we discuss various possible mechanisms of the pathogenesis of pain in PDN. We discuss the role of hyperglycaemia in altering the physiology of peripheral nerves. We also describe central mechanisms of pain.
Hereditary sensory and autonomic neuropathies (HSN/HSAN) are clinically and genetically heterogeneous disorders of the peripheral nervous system that predominantly affect the sensory and autonomic neurons. Hallmark features comprise not only prominent sensory signs and symptoms and ulcerative mutilations but also variable autonomic and motor disturbances. Autosomal dominant and autosomal recessive inheritance has been reported. Molecular genetics studies have identified disease-causing mutations in 11 genes. Some of the affected proteins have nerve-specific roles but underlying mechanisms have also been shown to involve sphingolipid metabolism, vesicular transport, structural integrity, and transcription regulation. Genetic and functional studies have substantially improved the understanding of the pathogenesis of the HSN/HSAN and will help to find preventive and causative therapies in the future.
... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Lake Michigan Shore. 9.79... Michigan Shore. (a) Name. The name of the viticultural area described in this section is “Lake Michigan Shore.” (b) Approved maps. The appropriate maps for determining the boundaries of the Lake...
... mineral extraction. (3) Michigan Solid Waste Regulations pertaining to solid waste management, MCL section....700 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR PROGRAMS FOR THE CONDUCT OF SURFACE MINING OPERATIONS WITHIN EACH STATE MICHIGAN § 922.700 Michigan Federal...
Michigan State Advisory Committee to the U.S. Commission on Civil Rights.
This report is a summary statement of the Michigan Advisory Committee's study on civil rights issues facing Arab American communities in Michigan. It is based on information received by the Committee at a community forum held in Dearborn, Michigan, in 1999. Six sections focus on: (1) "Introduction," including Arab American demographics…
Miller, R G; Gutmann, L; Lewis, R A; Sumner, A J
The electrophysiologic differences between chronic acquired demyelinative neuropathy and the demyelinative form of Charcot-Marie-Tooth disease have recently been reported. The present report extends these observations to include the genetically determined demyelinating neuropathies seen in metachromatic leukodystrophy, Krabbe's leukodystrophy, and Cockayne's syndrome. The electrophysiologic features of metachromatic leukodystrophy (five patients), Krabbe's (four patients), and Cockayne's syndrome (three patients) were all similar. There was uniform slowing of conduction (both in different nerves and in different nerve segments), and conduction block was not seen. These findings are consistent with a uniform degree of demyelination in multiple nerves and throughout the entire length of individual axons. Thus, uniform slowing of nerve conduction constitutes strong evidence for a familial demyelinative neuropathy, as opposed to the multifocal slowing seen in acute and chronic acquired demyelinative neuropathy.
De Giorgio, Roberto; Bianco, Francesca; Latorre, Rocco; Caio, Giacomo; Clavenzani, Paolo; Bonora, Elena
Enteric neuropathy is a term indicating an impairment of the innervation supplying the gastrointestinal tract. The clinical phenotypes of the enteric neuropathies are the 'tip of the iceberg' of severe functional digestive diseases, such as intestinal pseudo-obstruction syndromes (e.g., chronic intestinal pseudo-obstruction). Despite progress acquired over the years, the pathogenetic mechanisms leading to enteric neuropathies are still far from being elucidated and the therapeutic approaches to these patients are mainly supportive, rather than curative.The purpose of this chapter is to review the advancements that have been done in the knowledge of enteric neuropathies identified in adult patients ('tomorrow'), going through where we currently are ('today') following a brief history of the major milestones on the pioneering discoveries in the field ('yesterday').
Jolivalt, Corinne G; Frizzi, Katie E; Guernsey, Lucie; Marquez, Alex; Ochoa, Joseline; Rodriguez, Maria; Calcutt, Nigel A
Peripheral neuropathy is a frequent complication of chronic diabetes that most commonly presents as a distal degenerative polyneuropathy with sensory loss. Around 20% to 30% of such patients may also experience neuropathic pain. The underlying pathogenic mechanisms are uncertain, and therapeutic options are limited. Rodent models of diabetes have been used for more than 40 years to study neuropathy and evaluate potential therapies. For much of this period, streptozotocin-diabetic rats were the model of choice. The emergence of new technologies that allow relatively cheap and routine manipulations of the mouse genome has prompted increased use of mouse models of diabetes to study neuropathy. In this article, we describe the commonly used mouse models of type 1 and type 2 diabetes, and provide protocols to phenotype the structural, functional, and behavioral indices of peripheral neuropathy, with a particular emphasis on assays pertinent to the human condition. © 2016 by John Wiley & Sons, Inc.
Pain modulation is a key treatment goal for diabetic peripheral neuropathy patients. Guidelines have recommended antidepressant, anticonvulsant, analgesic, and topical medications—both approved and off-label—to reduce pain in this population.
... particular ethnic groups? Genetic Changes Mutations in the SCN9A or SCN10A gene can cause small fiber neuropathy . ... pieces (the alpha subunits) of sodium channels. The SCN9A gene instructs the production of the alpha subunit ...
Maksimova, M Yu; Sineva, N A; Vodopyanov, N P
Neuralgia (neuropathy) is the most common manifestation of herpes zoster (HZ). In spinal and cranial neuralgia, there are 3 types of pain: 1) spontaneous, persistent, burning pain; 2) intermittent sharp pain; 3) pain occurring with nonpainful stimulation. The skin exhibits areas of hypesthesia, anesthesia, and dysesthesia. Ophthalmic neuralgia (of the first branch of the trigeminal nerve) is encountered in 20% of HZ cases. HZ of the auricle and external auditory meatus concurrent with facial and vestibulocochlear neuropathy is diagnosed as Ramsay Hunt syndrome. Postherpetic neuralgia (neuropathy) is characterized by pain present for 3 months or more after the appearance of herpetic eruptions. Combined therapy involving the earlier use of antiviral agents, tricyclic antidepressants, analgesics, and neuromidine is the most effective option for HZ-induced neuralgia (neuropathy).
KLEIN, CHRISTOPHER J.; DUAN, XIAOHUI; SHY, MICHAEL E.
Inherited neuropathy is a group of common neurologic disorders with heterogeneous clinical presentations and genetic causes. Detailed neuromuscular evaluations, including nerve conduction studies, laboratory testing, and histopathologic examination, can assist in identification of the inherited component beyond family history. Genetic testing increasingly enables definitive diagnosis of specific inherited neuropathies. Diagnosis, however, is often complex, and neurologic disability may have both genetic and acquired components in individual patients. The decision of which genetic test to order or whether to order genetic tests is often complicated, and the strategies to maximize the value of testing are evolving. Apart from rare inherited metabolic neuropathies, treatment approaches remain largely supportive. We provide a clinical update of the various types of inherited neuropathies, their differential diagnoses, and distinguishing clinical features (where available). A framework is provided for clinical evaluations, including the inheritance assessment, electrophysiologic examinations, and specific genetic tests. PMID:23801417
Vasculitic neuropathies are caused by ischemic damage due to vessel wall inflammation. This damage may cause axonal degeneration leading to permanent neurological disabilities. Therefore, early initiation of effective treatment is crucial. For primary systemic vasculitis, a combined treatment of corticosteroid and immunosuppressive agents is recommended in the evidence-based guidelines as initial standard therapy for induction of remission. However, limited data are available regarding therapies for vasculitic neuropathies and it remains unclear whether combined treatment should be employed as an initial therapy for all patients with vasculitic neuropathies. In approximately half the patients with vasculitic neuropathies, monotherapy with corticosteroids is insufficient in preventing long-lasting neurological disabilities. Addition of intravenous immunoglobulin at an early stage of the disease may be a promising treatment option obviating the need for potent but potentially harmful immunosuppressive agents in some mild or localized cases.
This review focuses on the actual status and recent advances in the treatment of immune-mediated neuropathies, including: Guillain-Barre syndrome (GBS) with its subtypes acute inflammatory demyelinating polyradiculoneuropathy, acute motor axonal neuropathy, acute motor and sensory axonal neuropathy, Miller Fisher syndrome, and acute pandysautonomia; chronic inflammatory demyelinating polyneuropathy (CIDP) with its subtypes classical CIDP, CIDP with diabetes, CIDP/monoclonal gammopathy of undetermined significance (MGUS), sensory CIDP, multifocal motor neuropathy (MMN), multifocal acquired demyelinating sensory and motor neuropathy or Lewis-Sumner syndrome, multifocal acquired sensory and motor neuropathy, and distal acquired demyelinating sensory neuropathy; IgM monoclonal gammopathies with its subtypes Waldenstrom's macroglobulinemia, myelin-associated glycoprotein-associated gammopathy, polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome, mixed cryoglobulinemia, gait ataxia, late-onset polyneuropathy syndrome, and MGUS. Concerning the treatment of GBS, there is no significant difference between intravenous immunoglobulins (IVIG), plasma exchange or plasma exchange followed by IVIG. Because of convenience and absent invasiveness, IVIG are usually preferred. In treating CIDP corticosteroids, IVIG, or plasma exchange are equally effective. Despite the high costs and relative lack of availability, IVIG are preferentially used. For the one-third of patients, who does not respond, other immunosuppressive options are available. In MMN IVIG are the treatment of choice. Inadequate response in 20% of the patients requires adjunctive immunosuppressive therapies. Neuropathies with IgM monoclonal gammopathy may respond to various chemotherapeutic agents, although the long-term effects are unknown. In addition, such treatment may be associated with serious side effects. Recent data support the use of rituximab, a monoclonal antibody against the B
Cardiovascular autonomic neuropathy is frequently observed in patients with diabetes mellitus and encompasses damage to the autonomic nerve fibers, resulting in abnormalities in heart rate control and vascular dynamics. There is an increased mortality and morbidity rate among these patients. A series of cardiovascular reflex tests known as Ewing's battery tests are used for diagnosis cardiac autonomic neuropathy and provide valuable information to the clinical assessment of these patients. As...
McClelland, Collin M; Van Stavern, Gregory P; Tselis, Alex C
Leber hereditary optic neuropathy (LHON) is rarely associated with multiple sclerosis-like features. We present a case of a 65-year-old African American woman with LHON masquerading as neuromyelitis optica (NMO). We highlight the features of the clinical examination and MRI that were suggestive of an alternative diagnosis and review the literature regarding LHON and multiple sclerosis. The diagnosis of LHON should be considered in all cases of acute or subacute bilateral optic neuropathy, including presumed seronegative NMO.
Parry, G J; Bredesen, D E
We describe 16 patients with neuropathy associated with pyridoxine abuse. The clinical picture of a pure sensory central-peripheral distal axonopathy was consistent. Pyridoxine dose was 0.2 to 5 g/d, and duration of consumption before symptoms was inversely proportional to the daily intake. In all patients with adequate follow-up, improvement followed discontinuation of pyridoxine. The ready availability of up to 1-gram tablets makes it likely that this neuropathy will continue to be seen.
Dordain, G; Deffond, D
Daily needs of vitamin B6 are very low (2 mg per day) and widely covered by normal feeding. Pyridoxine deficiencies are exceptional (congenital metabolic abnormalities, drug or toxic-induced perturbations). First described in animal models, human cases of neuropathy had been encountered in the "megavitamin"-syndrome. They are confirmed by rare case-reports of very high doses given in toxic indication. Sensory peripheral neuropathies can also occur with lower doses taken over a long period of time.
experimental situations insufficient contraction of resistance vessels has been demonstrated. The vasoconstrictor defects demonstrated are of a magnitude sufficient to account for the prevailing hypotension. Furthermore, during exercise cardiac output is low in patients with autonomic neuropathy, a finding...... blood pressure fall ensues in patients with autonomic neuropathy, probably due to excessive muscular vasodilation. It is unresolved why blood pressure regulation is intact during hypoglycemia and severely impaired--at similar catecholamine concentrations--during epinephrine infusions....
The Lake Michigan Level 3 (LM3) Model is a numerical model of Lake Michigan used to predict the fate and transport of 54 PCB congeners. The LM3 model segments Lake Michigan horizontally with a 5 x 5 km grid and vertically with 19 sigma layers for a total of 44,042 water column se...
Vallat, J.-M.; Tabaraud, F.; Magy, L.; Macian, F.
The Chronic Inflammatory Demyelinating Polyradiculoneuropathies (CIDP) constitute a syndrome whose incidence is difficult to evaluate, and is probably underestimated. In the course of this presentation, we deliberately restricted discussion to issues raised in recent years concerning the extent of this syndrome. We discuss diagnostic criteria, especially electrophysiological ones. As the criteria proposed by the ad hoc committee of the American Academy of Neurology in 1991 have been questioned due to lack of sensitivity, new ones have been proposed recently. We briefly discuss the different types of chronic dysimmune demyelinating neuropathy: not only the CIDP, but also the Lewis and Sumner syndrome or multifocal inflammatory demyelinating neuropathy and the multiple conduction block neuropathies. At last, we point out the consistent finding of axonal involvement in the course of a chronic demyelinating neuropathy; over time, it can become predominant, which may make diagnosis difficult by suggesting a chronic axonal neuropathy that may be assumed to be primary. Consideration of these points may help clinicians recognize more chronic dysimmune neuropathies, for which immunosuppressive therapy has been found to be effective.
Lopez Sanchez, M I G; Crowston, J G; Mackey, D A; Trounce, I A
Optic neuropathies are an important cause of blindness worldwide. The study of the most common inherited mitochondrial optic neuropathies, Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA) has highlighted a fundamental role for mitochondrial function in the survival of the affected neuron-the retinal ganglion cell. A picture is now emerging that links mitochondrial dysfunction to optic nerve disease and other neurodegenerative processes. Insights gained from the peculiar susceptibility of retinal ganglion cells to mitochondrial dysfunction are likely to inform therapeutic development for glaucoma and other common neurodegenerative diseases of aging. Despite it being a fast-evolving field of research, a lack of access to human ocular tissues and limited animal models of mitochondrial disease have prevented direct retinal ganglion cell experimentation and delayed the development of efficient therapeutic strategies to prevent vision loss. Currently, there are no approved treatments for mitochondrial disease, including optic neuropathies caused by primary or secondary mitochondrial dysfunction. Recent advances in eye research have provided important insights into the molecular mechanisms that mediate pathogenesis, and new therapeutic strategies including gene correction approaches are currently being investigated. Here, we review the general principles of mitochondrial biology relevant to retinal ganglion cell function and provide an overview of the major optic neuropathies with mitochondrial involvement, LHON and ADOA, whilst highlighting the emerging link between mitochondrial dysfunction and glaucoma. The pharmacological strategies currently being trialed to improve mitochondrial dysfunction in these optic neuropathies are discussed in addition to emerging therapeutic approaches to preserve retinal ganglion cell function.
Pasnoor, Mamatha; Dimachkie, Mazen M; Kluding, Patricia; Barohn, Richard J
Diabetes is the most common cause of neuropathy in United States and neuropathies are the most common complication of diabetes mellitus, affecting up to 50% of patients with type 1 and type 2 diabetes mellitus. Symptoms usually include numbness, tingling, pain, and weakness. Dizziness with postural changes can be seen with autonomic neuropathy. Metabolic, vascular, and immune theories have been proposed for the pathogenesis of diabetic neuropathy. Axonal damage and segmental demyelination can be seen with diabetic neuropathies. Management of diabetic neuropathy should begin at the initial diagnosis of diabetes and mainly requires tight and stable glycemic control.
Secion 107, Alternative 1 Program Year (Budget EC): Effective Price Level Date: COST CNTG CNTG TOTAL ESC COST CNTG __1l!SL _fi!SL __(_’M_ _j!!$l_...Michigan College Secion 107, Alternative 1 Estimate Prepared : Effective Price Level: WBS Civil Works NUMBER Feature & Sub-Feature Descri1;1tion A B...William D. Merte, This Estimate reflects the scope and schedule in report; Feasibility Study, North West Michigan College Secion 107, Alternative 1
Meijer, J.W.; Lefrandt, J.D.; Links, T.P.; Smit, J.A.; Stewart, R.E.; van der Hoeven, J.H.; Hoogenberg, K.
OBJECTIVE - To evaluate the discriminative power of the Diabetic Neuropathy Symptom (DNS) and Diabetic Neuropathy Examination (DNE) scores for diagnosing diabetic polyneuropathy (PNP), as well as their relation with cardiovascular autonomic function testing (cAFT) and electro-diagnostic studies (EDS
Michigan State Dept. of Education, Lansing.
In operation since 1988, the Michigan School Readiness Program (MSRP) provides high-quality preschool programs for children who may be at risk of becoming educationally disadvantaged and who may have needs for special assistance. This manual provides guidelines for implementing all aspects of the program, including applying for funding, recruiting…
... Mile Road to Kelly Road, N. to 15 Mile Road to Hayes Road, S. to 14 Mile Road to Clawson City Boundary... June 15, 2005 for all areas in Michigan. The Detroit-Ann Arbor, Flint, Grand Rapids, Muskegon, Allegan... is 90 days after January 5, 2005, unless otherwise noted. Michigan—PM2.5 Designated area...
... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS ADMINISTRATION Michigan Disaster MI-00039 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY... INFORMATION CONTACT: A. Escobar, Office of Disaster Assistance, U.S. Small Business Administration, 409...
Voght, Geoffrey M.
The commercial Spanish courses at Eastern Michigan University, examinations in commercial Spanish, and cooperative education exchange programs are described, and the university's new programs that combine the study of foreign language and business are briefly addressed. A six-course sequence offered on the junior, senior, and graduate levels cover…
This brochure provides an overview of the challenges and successes of Ann Arbor, Michigan, a 2007 Solar America City awardee, on the path toward becoming a solar-powered community. Accomplishments, case studies, key lessons learned, and local resource information are given.
Full Text Available Background. Sensory neuropathy (SN is one of the most common AIDS-associated neurologic disorders especially in the era of highly active antiretroviral therapy (HAART. The aim of this study was to determine the prevalence of SN among highly-active-antiretroviral-therapy- (HAART- experienced and HAART-naïve HIV-positive individuals and to investigate the relationship to demographic, clinical, and laboratory factors. Methods. 323 patients with HIV infection (142 on HAART and 181 HAART naïve were enrolled in a cross-sectional neuropathy screening program. Data was collected using structured questionnaires which contained the brief peripheral neuropathy screening tool of AIDS Clinical Trial Group protocol. Neuropathy was defined by the presence of at least 1 clinical sign in a distal, symmetrical pattern. Patients were classified as symptomatic if they described aching, stabbing, or burning pain, paresthesia, or numbness in a similar distribution. Demographic, clinical, and laboratory details were documented as risk factors. Result. The prevalence of sensory neuropathy was 39.0% (126/323, (of which 29/126 (23% were symptomatic. Amongst those on HAART, 60/142 (42.3% had SN compared to 66/181 (36.5% HAART-naïve individuals (P=0.29. On multivariate analyses, the independent associations with SN were increasing age (P=0.03 and current exposure to stavudine (P=0.00. Gender (P=0.99 height (P=0.07 use of HAART (P=0.50, duration of HAART treatment (P=0.10, and lower CD4 count (P=0.12 were not associated with an increased SN risk. Conclusion. HIV SN remains common despite improved immunologic function associated with HAART and decreased neurotoxic HAART use. In this cross-sectional analysis, age and stavudine-based therapies were the independent risk factors.
Dimitropoulos, Gerasimos; Tahrani, Abd A; Stevens, Martin J
Cardiac autonomic neuropathy (CAN) is an often overlooked and common complication of diabetes mellitus. CAN is associated with increased cardiovascular morbidity and mortality. The pathogenesis of CAN is complex and involves a cascade of pathways activated by hyperglycaemia resulting in neuronal ischaemia and cellular death. In addition, autoimmune and genetic factors are involved in the development of CAN. CAN might be subclinical for several years until the patient develops resting tachycardia, exercise intolerance, postural hypotension, cardiac dysfunction and diabetic cardiomyopathy. During its sub-clinical phase, heart rate variability that is influenced by the balance between parasympathetic and sympathetic tones can help in detecting CAN before the disease is symptomatic. Newer imaging techniques (such as scintigraphy) have allowed earlier detection of CAN in the pre-clinical phase and allowed better assessment of the sympathetic nervous system. One of the main difficulties in CAN research is the lack of a universally accepted definition of CAN; however, the Toronto Consensus Panel on Diabetic Neuropathy has recently issued guidance for the diagnosis and staging of CAN, and also proposed screening for CAN in patients with diabetes mellitus. A major challenge, however, is the lack of specific treatment to slow the progression or prevent the development of CAN. Lifestyle changes, improved metabolic control might prevent or slow the progression of CAN. Reversal will require combination of these treatments with new targeted therapeutic approaches. The aim of this article is to review the latest evidence regarding the epidemiology, pathogenesis, manifestations, diagnosis and treatment for CAN.
Menezes, Manoj P; Ouvrier, Robert A
Mitochondrial diseases in children are often associated with a peripheral neuropathy but the presence of the neuropathy is under-recognized because of the overwhelming involvement of the central nervous system (CNS). These mitochondrial neuropathies are heterogeneous in their clinical, neurophysiological, and histopathological characteristics. In this article, we provide a comprehensive review of childhood mitochondrial neuropathy. Early recognition of neuropathy may help with the identification of the mitochondrial syndrome. While it is not definite that the characteristics of the neuropathy would help in directing genetic testing without the requirement for invasive skin, muscle or liver biopsies, there appears to be some evidence for this hypothesis in Leigh syndrome, in which nuclear SURF1 mutations cause a demyelinating neuropathy and mitochondrial DNA MTATP6 mutations cause an axonal neuropathy. POLG1 mutations, especially when associated with late-onset phenotypes, appear to cause a predominantly sensory neuropathy with prominent ataxia. The identification of the peripheral neuropathy also helps to target genetic testing in the mitochondrial optic neuropathies. Although often subclinical, the peripheral neuropathy may occasionally be symptomatic and cause significant disability. Where it is symptomatic, recognition of the neuropathy will help the early institution of rehabilitative therapy. We therefore suggest that nerve conduction studies should be a part of the early evaluation of children with suspected mitochondrial disease.
Full Text Available PURPOSE: Patients with ulnar neuropathy of unclear etiology occasionally present with lesion extension from elbow to upper arm level on MRI. This study investigated whether MRI thereby distinguishes multifocal neuropathy from focal-compressive neuropathy at the elbow. METHODS: This prospective study was approved by the institutional ethics committee and written informed consent was obtained from all participants. 122 patients with ulnar mononeuropathy of undetermined localization and etiology by clinical and electrophysiological examination were assessed by MRI at upper arm and elbow level using T2-weighted fat-saturated sequences at 3T. Twenty-one patients were identified with proximal ulnar nerve lesions and evaluated for findings suggestive of disseminated neuropathy (i subclinical lesions in other nerves, (ii unfavorable outcome after previous decompressive elbow surgery, and (iii subsequent diagnosis of inflammatory or other disseminated neuropathy. Two groups served as controls for quantitative analysis of nerve-to-muscle signal intensity ratios: 20 subjects with typical focal ulnar neuropathy at the elbow and 20 healthy subjects. RESULTS: In the group of 21 patients with proximal ulnar nerve lesion extension, T2-w ulnar nerve signal was significantly (p<0.001 higher at upper arm level than in both control groups. A cut-off value of 1.92 for maximum nerve-to-muscle signal intensity ratio was found to be sensitive (86% and specific (100% to discriminate this group. Ten patients (48% exhibited additional T2-w lesions in the median and/or radial nerve. Another ten (48% had previously undergone elbow surgery without satisfying outcome. Clinical follow-up was available in 15 (71% and revealed definitive diagnoses of multifocal neuropathy of various etiologies in four patients. In another eight, diagnoses could not yet be considered definitive but were consistent with multifocal neuropathy. CONCLUSION: Proximal ulnar nerve T2 lesions at upper
Klebe, Stephan; Depienne, Christel; Gerber, Sylvie; Challe, Georges; Anheim, Mathieu; Charles, Perrine; Fedirko, Estelle; Lejeune, Elodie; Cottineau, Julien; Brusco, Alfredo; Dollfus, Hélène; Chinnery, Patrick F; Mancini, Cecilia; Ferrer, Xavier; Sole, Guilhem; Destée, Alain; Mayer, Jean-Michel; Fontaine, Bertrand; de Seze, Jérôme; Clanet, Michel; Ollagnon, Elisabeth; Busson, Philippe; Cazeneuve, Cécile; Stevanin, Giovanni; Kaplan, Josseline; Rozet, Jean-Michel; Brice, Alexis; Durr, Alexandra
Mutations in the spastic paraplegia 7 (SPG7) gene encoding paraplegin are responsible for autosomal recessive hereditary spasticity. We screened 135 unrelated index cases, selected in five different settings: SPG7-positive patients detected during SPG31 analysis using SPG31/SPG7 multiplex ligation-dependent probe amplification (n = 7); previously reported ambiguous SPG7 cases (n = 5); patients carefully selected on the basis of their phenotype (spasticity of the lower limbs with cerebellar signs and/or cerebellar atrophy on magnetic resonance imaging/computer tomography scan and/or optic neuropathy and without other signs) (n = 24); patients with hereditary spastic paraparesis referred consecutively from attending neurologists and the national reference centre in a diagnostic setting (n = 98); and the index case of a four-generation family with autosomal dominant optic neuropathy but no spasticity linked to the SPG7 locus. We identified two SPG7 mutations in 23/134 spastic patients, 21% of the patients selected according to phenotype but only 8% of those referred directly. Our results confirm the pathogenicity of Ala510Val, which was the most frequent mutation in our series (65%) and segregated at the homozygous state with spastic paraparesis in a large family with autosomal recessive inheritance. All SPG7-positive patients tested had optic neuropathy or abnormalities revealed by optical coherence tomography, indicating that abnormalities in optical coherence tomography could be a clinical biomarker for SPG7 testing. In addition, the presence of late-onset very slowly progressive spastic gait (median age 39 years, range 18-52 years) associated with cerebellar ataxia (39%) or cerebellar atrophy (47%) constitute, with abnormal optical coherence tomography, key features pointing towards SPG7-testing. Interestingly, three relatives of patients with heterozygote SPG7 mutations had cerebellar signs and atrophy, or peripheral neuropathy, but no spasticity of the lower
Full Text Available Neuropad is currently a categorical visual screening test that identifies diabetic patients at risk of foot ulceration. The diagnostic performance of Neuropad was compared between the categorical and continuous (image-analysis (Sudometrics outputs to diagnose diabetic peripheral neuropathy (DPN. 110 subjects with type 1 and 2 diabetes underwent assessment with Neuropad, Neuropathy Disability Score (NDS, peroneal motor nerve conduction velocity (PMNCV, sural nerve action potential (SNAP, Deep Breathing-Heart Rate Variability (DB-HRV, intraepidermal nerve fibre density (IENFD, and corneal confocal microscopy (CCM. 46/110 patients had DPN according to the Toronto consensus. The continuous output displayed high sensitivity and specificity for DB-HRV (91%, 83%, CNFD (88%, 78%, and SNAP (88%, 83%, whereas the categorical output showed high sensitivity but low specificity. The optimal cut-off points were 90% for the detection of autonomic dysfunction (DB-HRV and 80% for small fibre neuropathy (CNFD. The diagnostic efficacy of the continuous Neuropad output for abnormal DB-HRV (AUC: 91%, P=0.0003 and CNFD (AUC: 82%, P=0.01 was better than for PMNCV (AUC: 60%. The categorical output showed no significant difference in diagnostic efficacy for these same measures. An image analysis algorithm generating a continuous output (Sudometrics improved the diagnostic ability of Neuropad, particularly in detecting autonomic and small fibre neuropathy.
This short review highlights five studies published in 2012 in the field of Charcot-Marie-Tooth disease (CMT) and transthyretin familial amyloid neuropathies (TTR-FAN). Regarding CMT, an Australian pediatric study shows the high prevalence of impaired speech perception and hearing disability in children with CMT1 or CMT2 with normal or near normal audiometry (Rance et al., 2012). In a second study, the clinical and electrophysiological characteristics of 14 patients with CMT4C due to mutations in SH3TC2 gene are described (Yger et al., 2012). The 3 clinical hallmarks of CMT4C patients in this French cohort are the high prevalence of scoliosis, the proximal motor weakness and the cranial nerves involvement. Concerning TTR-FAN, the first data from French and international registries are reported (Adams et al., 2012; Coelho et al., 2013) and a phase II trial describes the results of taurourodeoxycholic acid and doxycycline treatment (Obici et al., 2012).
Srinivasan, Jayashri; Escolar, Diane; Ryan, Monique; Darras, Basil; Jones, H. Royden
Four cases of pediatric sciatic neuropathies due to unusual vascular mechanisms are reported. Pediatric sciatic neuropathies were seen after umbilical artery catheterization, embolization of arteriovenous malformation, meningococcemia, and hypereosinophilic vasculitis. Electrophysiologic studies dem
Srinivasan, Jayashri; Escolar, Diane; Ryan, Monique; Darras, Basil; Jones, H. Royden
Four cases of pediatric sciatic neuropathies due to unusual vascular mechanisms are reported. Pediatric sciatic neuropathies were seen after umbilical artery catheterization, embolization of arteriovenous malformation, meningococcemia, and hypereosinophilic vasculitis. Electrophysiologic studies
Mäurer, M; Toyka, K V; Martini, R
Hereditary neuropathies, e.g., Charcot-Marie-Tooth (CMT) disease, are inherited diseases of the peripheral nervous system causing chronic progressive motor and sensory dysfunction. Most neuropathies are due to mutations in myelin genes such as PMP22, P0, and the gap junction protein Cx32. Myelin mutant mice are regarded as suitable animal models for several forms of hereditary neuropathies and are important neurobiological tools for the evaluation of pathogenetic and therapeutic concepts in hereditary neuropathies. Using these animal models we could recently show that the immune system is involved in the pathogenesis of hereditary neuropathies. Due to the phenotypic similarities we also consider the immune system important for human inherited neuropathies, in particular since several case reports demonstrate a beneficial effect of immune therapies in patients with hereditary neuropathies. In this review we compare findings from animal models and human disease to elucidate the role of the immune system in hereditary neuropathies.
Sarker, U K; Uddin, M J; Chowdhury, R; Roy, N; Bhattacharjee, M; Roy, J
The objectives of the study were to see the association of peripheral neuropathy in leprosy and to find out the clinical profile of peripheral neuropathy and disability status in leprosy. It was descriptive type of cross sectional study was conducted among the cases of leprosy attended in the out-patient departments of neurology, Mymensingh Medical College Hospital (MMCH) and Mymensingh tuberculosis and leprosy hospital that fulfilled the inclusion criteria were included in this study, during the study period of January 2010 to December 2011.In this study of 62 cases revealed that leprosy is more common in male (71%) people and 21% leprosy patient had contact with known case of leprosy. Leprosy causes peripheral neuropathy (61.3%). Duration of occurrence of peripheral neuropathy was prolonged (>6 month) in most of the patients (47.4%) and the disease progression was also slow (63.2%). Numbness was complained by 89.4% patients and 65.8% subjects complained of weakness of limbs. Deformities and ulcers were present in 26.3% and 50% of patients respectively. Ulnar nerve (43.6%), Lateral popliteal nerve (41.9%), Posterior tibial nerve (41.9%) and Great auricular nerve (17.7%) were the most commonly involved thickened peripheral nerves. The rate of visible physical impairment (WHO Grade 2 disability) among people affected by leprosy in feet was 27.4% and in hands was 16.1%. The position and vibration sense was found to normal all patients of peripheral neuropathy.
Calcutt, Nigel A.; Lopez, Veronica L.; Bautista, Arjel D.; Mizisin, Leah M.; Torres, Brenda R.; Shroads, Albert L.; Mizisin, Andrew P.; Stacpoole, Peter W.
The use of dichloroacetate (DCA) for treating patients with mitochondrial diseases is limited by the induction of peripheral neuropathy. The mechanisms of DCA-induced neuropathy are not known. Oral DCA treatment (50–500 mg/kg/day for up to 16 weeks) induced tactile allodynia in both juvenile and adult rats; concurrent thermal hypoalgesia developed at higher doses. Both juvenile and adult rats treated with DCA developed nerve conduction slowing that was more pronounced in adult rats. No overt axonal or glial cell abnormalities were identified in peripheral nerves or spinal cord of any DCA-treated rats but morphometric analysis identified a reduction of mean axonal caliber of peripheral nerve myelinated fibers. DCA treatment also caused accumulation of oxidative stress markers in the nerves. These data indicate that behavioral, functional and structural indices of peripheral neuropathy may be induced in both juvenile and adult rats treated with DCA at doses similar to those in clinical use. DCA-induced peripheral neuropathy primarily afflicts axons and involves both metabolic and structural disorders. The DCA-treated rat may provide insight into the pathogenesis of peripheral neuropathy and facilitate development of adjuvant therapeutics to prevent this disorder that currently restricts the clinical use of DCA. PMID:19680144
Fernyhough, Paul; Calcutt, Nigel A
Abnormal neuronal calcium (Ca2+) homeostasis has been implicated in numerous diseases of the nervous system. The pathogenesis of two increasingly common disorders of the peripheral nervous system, namely neuropathic pain and diabetic polyneuropathy, has been associated with aberrant Ca2+ channel expression and function. Here we review the current state of knowledge regarding the role of Ca2+ dyshomeostasis and associated mitochondrial dysfunction in painful and diabetic neuropathies. The central impact of both alterations of Ca2+ signalling at the plasma membrane and also intracellular Ca2+ handling on sensory neurone function is discussed and related to abnormal endoplasmic reticulum performance. We also present new data highlighting sub-optimal axonal Ca2+ signalling in diabetic neuropathy and discuss the putative role for this abnormality in the induction of axonal degeneration in peripheral neuropathies. The accumulating evidence implicating Ca2+ dysregulation in both painful and degenerative neuropathies, along with recent advances in understanding of regional variations in Ca2+ channel and pump structures, makes modulation of neuronal Ca2+ handling an increasingly viable approach for therapeutic interventions against the painful and degenerative aspects of many peripheral neuropathies.
Dalakas, Marinos C
Autoimmune neuropathies occur when immunologic tolerance to myelin or axonal antigens is lost. Even though the triggering factors and the underling immunopathology have not been fully elucidated in all neuropathy subsets, immunological studies on the patients' nerves, transfer experiments with the patients' serum or intraneural injections, and molecular fingerprinting on circulating autoantibodies or autoreactive T cells, indicate that cellular and humoral factors, either independently or in concert with each other, play a fundamental role in their cause. The review is focused on the main subtypes of autoimmune neuropathies, mainly the Guillain-Barré syndrome(s), the Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), the Multifocal Motor Neuropathy (MMN), and the IgM anti-MAG-antibody mediated neuropathy. It addresses the factors associated with breaking tolerance, examines the T cell activation process including co-stimulatory molecules and key cytokines, and discusses the role of antibodies against peripheral nerve glycolipids or glycoproteins. Special attention is given to the newly identified proteins in the nodal, paranodal and juxtaparanodal regions as potential antigenic targets that could best explain conduction failure and rapid recovery. New biological agents against T cells, cytokines, B cells, transmigration and transduction molecules involved in their immunopathologic network, are discussed as future therapeutic options in difficult cases. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis.
Maresca, A; Caporali, L; Strobbe, D; Zanna, C; Malavolta, D; La Morgia, C; Valentino, M L; Carelli, V
Over two decades have elapsed since the first mtDNA point mutation was associated with Leber's hereditary optic neuropathy (LHON) in 1988. We have subsequently witnessed a substantial understanding of the molecular basis of hereditary optic neuropathies, as well as of their clinical features and pathogenic mechanisms. It became clear that the large majority of genetic optic neuropathies have a primary or an indirect involvement of mitochondrial functions, justifying the definition of "mitochondrial optic neuropathies". Despite this progress many unsolved features remain to be understood, such as incomplete penetrance and variable clinical expressivity in LHON and dominant optic atrophy (DOA), gender prevalence in LHON, and complex gene/environment interactions in both LHON and DOA. The most recent advancement in our understanding of the molecular basis of mitochondrial optic neuropathies is the topic of this review. In particular, we analyze the role that mitochondrial biogenesis may play in the compensatory mechanisms that underlie incomplete penetrance and clinical expressivity, a scenario relevant for the possible design of future therapeutic approaches. Copyright© Bentham Science Publishers; For any queries, please email at email@example.com.
Gasparotti, Roberto; Padua, Luca; Briani, Chiara; Lauria, Giuseppe
Technical advances are rapidly changing the clinical and instrumental approach to peripheral nerve diseases. Magnetic resonance neurography, diffusion tensor imaging and nerve ultrasonography are increasingly entering the diagnostic workup of peripheral neuropathies as tools that complement neurophysiology and enable investigation of proximal structures, such as plexuses and roots. Progress in the design of magnetic resonance scanners and sequences, and the development of high-frequency ultrasound probes mean that high-resolution peripheral nerve imaging is possible, enabling detailed examination of nerve size, morphology and internal fascicular structure that can integrate nerve conduction studies into clinical practice. In the growing field of small-fibre neuropathy, in which traditional nerve conduction studies are of little or no use, skin biopsy has become a reliable tool for diagnosis. Corneal confocal microscopy, nociceptive evoked potentials and microneurography are emerging techniques that are mainly used in clinical research settings, but have increasing relevance to clinical practice. We review these new and emerging techniques and their effects on diagnosis, treatment strategies and prognosis in a variety of peripheral neuropathies, including entrapments, brachial plexopathies, immune and inherited neuropathies, and small-fibre neuropathies. We discuss the most promising research findings and their potential for future application in clinical practice.
Diabetic peripheral neuropathy is considered to be a long-term complication of Diabetes Mellitus. This neuropathy is the most common form of peripheral neuropathy in the Western world and develops in about 50% of diabetes patients affected with either type I or type II diabetes. Despite advances in understanding metabolic causes of diabetic peripheral neuropathy, specific treatments against this complications are far from being used in therapy options. In this study we have eva...
Klein, Christopher J
Peripheral neuropathies have diverse acquired and inherited causes. The autoimmune neuropathies represent an important category where treatment is often available. There are overlapping signs and symptoms between autoimmune neuropathies and other forms. Making a diagnosis can be challenging and first assisted by electrophysiologic and sometimes pathologic sampling, with autoimmune biomarkers providing increased assistance. Here we provide a review of the autoimmune and inflammatory neuropathies, their available biomarkers, and approaches to treatment. Also discussed is new evidence to support a mechanism of autoimmune pain.
Fujita, K.; DeWolf, C. L.; Ruddock, J.; Svoboda, M. R.; Sinclair, J.; Schepke, C.; Waite, G. P.
MIQuakes is a K-14 educational seismograph network currently consisting of 17 schools, mostly located in Michigan's lower peninsula. It is operated under the auspices of the Michigan Earth Science Teachers Association (MESTA) and is part of the IRIS Seismographs in Schools program. Although individual teachers in Michigan have had instruments as early as 1992, MESTA formed MIQuakes in 2010 to support the development of activities associated with classroom seismology appropriate for grades 6-12 and relevant to the Midwest, using locally recorded data. In addition, the deployment of the EarthScope transportable array in Michigan during 2011-2014 offered a tie in with a national-level research program. Michigan State University (MSU) and Michigan Tech provide content and technical support. In keeping with MESTA's philosophy of 'teachers helping teachers,' MIQuakes became, first and foremost, a group supported by teachers. Earthquake 'alerts' initially issued by MSU, were soon taken over by teachers who took the initiative in alerting each other to events, especially those that occurred during the school day. In-service teachers and university faculty have jointly organized workshops at MSU and at MESTA conferences - with teachers increasingly providing activities for sharing and relating the program to the new national standards. Workshops held to date have covered such topics as recognizing arrivals, filtering, focal mechanisms, and the Tohoku earthquake. As the group has grown, the degree of involvement and level of expertise have become broader, resulting in very different expectations from different teachers. How to keep the network cohesive, yet meet the needs of the individual members, will be one of the challenges of the next few years. Three levels of involvement by teachers are seen in the near term: those who operate their own classroom seismometer (currently either the short-period IRIS AS-1 or the broadband EAS-S102 seismometers); those who stream a nearby
Sneha Ganu; Yesha Mehta
Dengue fever is a debilitating mosquito-borne disease caused by dengue virus. We reported a case of femoral compression neuropathy due to iliopsoas hematoma complicating dengue hemorrhagic fever. Iliopsoas muscle hematoma can cause femoral neuropathy with resultant pain and paralysis. Such manifestations are not well documented in the literature. The pathogenesis of hematoma and compressive neuropathy with its appropriate management is discussed.
Giordano, Carla; Iommarini, Luisa; Giordano, Luca; Maresca, Alessandra; Pisano, Annalinda; Valentino, Maria Lucia; Caporali, Leonardo; Liguori, Rocco; Deceglie, Stefania; Roberti, Marina; Fanelli, Francesca; Fracasso, Flavio; Ross-Cisneros, Fred N; D'Adamo, Pio; Hudson, Gavin; Pyle, Angela; Yu-Wai-Man, Patrick; Chinnery, Patrick F; Zeviani, Massimo; Salomao, Solange R; Berezovsky, Adriana; Belfort, Rubens; Ventura, Dora Fix; Moraes, Milton; Moraes Filho, Milton; Barboni, Piero; Sadun, Federico; De Negri, Annamaria; Sadun, Alfredo A; Tancredi, Andrea; Mancini, Massimiliano; d'Amati, Giulia; Loguercio Polosa, Paola; Cantatore, Palmiro; Carelli, Valerio
Leber's hereditary optic neuropathy is a maternally inherited blinding disease caused as a result of homoplasmic point mutations in complex I subunit genes of mitochondrial DNA. It is characterized by incomplete penetrance, as only some mutation carriers become affected. Thus, the mitochondrial DNA mutation is necessary but not sufficient to cause optic neuropathy. Environmental triggers and genetic modifying factors have been considered to explain its variable penetrance. We measured the mitochondrial DNA copy number and mitochondrial mass indicators in blood cells from affected and carrier individuals, screening three large pedigrees and 39 independently collected smaller families with Leber's hereditary optic neuropathy, as well as muscle biopsies and cells isolated by laser capturing from post-mortem specimens of retina and optic nerves, the latter being the disease targets. We show that unaffected mutation carriers have a significantly higher mitochondrial DNA copy number and mitochondrial mass compared with their affected relatives and control individuals. Comparative studies of fibroblasts from affected, carriers and controls, under different paradigms of metabolic demand, show that carriers display the highest capacity for activating mitochondrial biogenesis. Therefore we postulate that the increased mitochondrial biogenesis in carriers may overcome some of the pathogenic effect of mitochondrial DNA mutations. Screening of a few selected genetic variants in candidate genes involved in mitochondrial biogenesis failed to reveal any significant association. Our study provides a valuable mechanism to explain variability of penetrance in Leber's hereditary optic neuropathy and clues for high throughput genetic screening to identify the nuclear modifying gene(s), opening an avenue to develop predictive genetic tests on disease risk and therapeutic strategies.
Chang, C W; Oh, S J
Posterior antebrachial cutaneous (PABC) neuropathy is rare. Two original cases are reported here. In case 1, the neuropathy is probably due to a traction injury in a reduction operation for humeral fracture. In case 2, it is injured associately with an operation in taking a myocutaneous flap. On examination, both cases showed a decreased sensation to pin-prick over the PABC nerve territories and a positive Tinel's sign near the injured sites. Sensory nerve conduction study of the PABC nerves revealed a low amplitude of the compound nerve action potential (CNAP) and a slow sensory nerve conduction velocity (SNCV) in case 1, and absent CNAP in case 2. Our study showed the sensory nerve conduction test is useful in confirming PABC neuropathy.
Theesen, K A; Marsh, W R
A 31-year-old woman with advanced diabetes mellitus with secondary autonomic and peripheral neuropathy was admitted for treatment of major depression. Previous therapy with desipramine resulted in exacerbation of the patient's orthostatic hypotension. After admission to the psychiatric facility she was initially stabilized medically and treated with psychotherapy. Subsequent treatment with low-dose fluoxetine 5 mg resulted in a decrease of the patient's diabetic neuropathy pain. Further increases in the fluoxetine dosage resulted in improvement of her depression and increased pain relief. Therapy with fluoxetine did not result in exacerbation of the orthostatic hypotension. This preliminary case report indicates that fluoxetine may be an alternative to the tricyclic antidepressants and trazodone in the treatment of diabetic peripheral neuropathy.
Biessels, G J; Bril, V; Calcutt, N A
of statistically different values between diabetic and control animals in 2 of 3 assessments (nocifensive behavior, nerve conduction velocities, or nerve structure). The participants propose that this framework would allow different research groups to compare and share data, with an emphasis on data targeted......NIDDK, JDRF, and the Diabetic Neuropathy Study Group of EASD sponsored a meeting to explore the current status of animal models of diabetic peripheral neuropathy. The goal of the workshop was to develop a set of consensus criteria for the phenotyping of rodent models of diabetic neuropathy....... The discussion was divided into five areas: (1) status of commonly used rodent models of diabetes, (2) nerve structure, (3) electrophysiological assessments of nerve function, (4) behavioral assessments of nerve function, and (5) the role of biomarkers in disease phenotyping. Participants discussed the current...
Full Text Available Cardiovascular autonomic neuropathy is frequently observed in patients with diabetes mellitus and encompasses damage to the autonomic nerve fibers, resulting in abnormalities in heart rate control and vascular dynamics. There is an increased mortality and morbidity rate among these patients. A series of cardiovascular reflex tests known as Ewing's battery tests are used for diagnosis cardiac autonomic neuropathy and provide valuable information to the clinical assessment of these patients. As anesthesia has a major influence on perioperative autonomic function, the interplay between cardiovascular autonomic neuropathy and anesthesia may result in unexpected haemodynamic instability during surgery and postoperative recovery. A comprehensive preoperative assessment and perioperative cautious monitoring are necessary for successful anesthesia management. [Archives Medical Review Journal 2016; 25(2.000: 140-151
Kahloun, Rim; Abroug, Nesrine; Ksiaa, Imen; Mahmoud, Anis; Zeghidi, Hatem; Zaouali, Sonia; Khairallah, Moncef
Different forms of optic neuropathy causing visual impairment of varying severity have been reported in association with a wide variety of infectious agents. Proper clinical diagnosis of any of these infectious conditions is based on epidemiological data, history, systemic symptoms and signs, and the pattern of ocular findings. Diagnosis is confirmed by serologic testing and polymerase chain reaction in selected cases. Treatment of infectious optic neuropathies involves the use of specific anti-infectious drugs and corticosteroids to suppress the associated inflammatory reaction. The visual prognosis is generally good, but persistent severe vision loss with optic atrophy can occur. This review presents optic neuropathies caused by specific viral, bacterial, parasitic, and fungal diseases. PMID:28539795
Full Text Available Context and Objective: In view of the growing burden of type 2 diabetes mellitus (T2DM globally and associated microvascular and macrovascular complications, the study was done to assess the prevalence and risk factors for diabetic neuropathy among T2DM patients attending a tertiary care hospital. Subjects and Methods: T2DM patients' ≥30 years of both gender, presenting to the Medicine Department at a tertiary care hospital were included in the study. Diabetic Neuropathy Symptom (DNS questionnaire to assess symptoms and Diabetic Neuropathy Examination (DNE scoring to assess clinical signs were used. Results: A total of 273 patients were included. The mean age was 57.8 ± 11.5 years. The male to female distribution was 75% (202 and 25% (71, respectively. According to DNS instrument, 41.4% patients scored positive for the presence of neuropathy while only 24.5% had neuropathy according to DNE score. The proportion of males affected by neuropathy was more than females. 43.1% males had a positive DNS score while only 27.2% of them had a positive DNE score. Duration of the disease was positively correlated with neuropathy. Neuropathy was more prevalent among people who had higher systolic and diastolic blood pressure as per DNS and DNE instruments. Conclusions: The present study identified a higher proportion of males to be affected by neuropathy. Hence, more detailed evaluation must be accorded to elderly male diabetic patients with longer duration of the disease. Lifestyle modifications and watchful screening need to be incorporated as part of routine patient health education during follow-up clinic visits.
Wise, Annabel G.; Bolin, Steven R.; Mullaney, Thomas P.; Kiupel, Matti; Maes, Roger K.
We report a disease outbreak in a Michigan rabbitry of a rabbit calicivirus distinct from the foreign animal disease agent, rabbit hemorrhagic disease virus (RHDV). The novel virus has been designated Michigan rabbit calicivirus (MRCV). Caliciviruses of the Lagovirus genus other than RHDV have not been described in US rabbit populations. The case-fatality rate was 32.5% (65/200). Clinical signs included hemorrhage and sudden death, with hepatic necrosis. Analysis of viral RNA sequence from >95% of the viral genome showed an average similarity of 79% with RHDV. Similarity of the predicted MRCV capsid amino acid sequence ranged from 89.8% to 91.3%, much lower than the 98% amino acid similarity between RHDV strains. Experimentally infected rabbits lacked clinical disease, but MRCV was detected in tissues by PCR. We propose that MRCV primarily causes subclinical infection but may induce overt RHD-like disease under certain field conditions. PMID:19961675
Sykam, Aparna; Gutlapalli, V R; Tenali, Sandeep P; Meena, A K; Chandran, Priscilla; Suneetha, Sujai; Suneetha, Lavanya M
Ceramide is a glycosphingolipid, a component of nerve and non neuronal cell membrane and plays a role in maintaining the integrity of neuronal tissue. Butyrylcholinesterase (BChE) is a multifunctional enzyme, its involvement in neurodegenerative diseases has been well established. Anticeramide antibody (Ab-Cer) and enzyme BChE have been implicated in peripheral neuropathies. The present study investigates whether there is an association between Ab-Cer and BChE activities and peripheral neuropathies. Patients included: human immunodeficiency virus associated peripheral neuropathy (HIV-PN, n=39), paucibacillary leprosy (PB-L, n=36), multibacillary leprosy (MB-L, n=52), diabetic neuropathy (DN, n=22), demyelinating sensory motor polyneuropathy (DSMN, n=13) and chronic inflammatory demyelinating polyneuropathy (CIDP, n=10). Plasma Ab-Cer was measured by indirect enzyme linked immune assay (ELISA) and BChE activity in plasma was measured by colorimetric method. Ab-Cer levels were significantly elevated in MB-L and DN as compared to healthy subjects (HS). BChE levels were significantly higher in MB-L and DN as well as in HIV and HIV-PN. There is no significant difference in either Ab-Cer or BChE levels in DSMN and CIDP. Elevated plasma Ab-Cer and BChE levels may be considered significant in the pathogenesis of neuropathies. The variation in concurrent involvement of both the molecules in the neuropathies of the study, suggest their unique involvement in neurodegenerative pathways. Copyright © 2017 Elsevier Ltd. All rights reserved.
Michigan Library, Lansing.
This document tabulates the results of a 1994 survey of public library funding in Michigan. The survey discovered that 68.8% of public library funds are provided by local tax support, 13.7% by penal fines awarded to libraries by court systems which have received income for violations of state laws, 7.6% by state aid, and 9.9% by other means, such…
Anheim, M; Tranchant, C
Inherited cerebellar ataxias constitute a complicated and heterogeneous group of neurodegenerative disorders affecting the cerebellum and/or spinocerebellar tract, spinal cord and peripheral nerves. A peripheral neuropathy is frequently seen in inherited cerebellar ataxias although it rarely reveals the disease. Moreover, the peripheral neuropathy is helpful for the diagnostic procedure and contributes to the functional prognosis of the disease. Thus, electroneuromyography is essential in the algorithm for the diagnosis of inherited cerebellar ataxias, as well as brain MRI (looking especially for cerebellar atrophy) and the assessment of several biomarkers (alpha-foetoprotein, vitamin E, albumin, LDL cholesterol, lactic acid, phytanic acid).
Garg, Kanwaljeet; Aggarwal, Ankita; Srivastava, Deep Narayan; Jana, Manisha; Sharma, Raju; Gamanagatti, Shivanand; Kumar, Atin; Kumar, Vijay; Malhotra, Rajesh; Goyal, Vinay; Garg, Kanwaljeet
Peripheral neuropathies refer to a group of disorders in which there is damage to the nerves of the peripheral nervous system. Electrophysiological studies are the main stay for the diagnosis of peripheral neuropathies. However, direct visualization of the nerves is possible with exact localization of site of pathology with high resolution ultrasonogram and 3 Tesla MRI scanner, and newer MR sequences. We did a cross sectional study including a total of 55 patients and 64 nerves with upper limb peripheral neuropathies. All the included patients underwent high resolution focused ultrasound of the nerves and MR neurography. Nerve Conduction Velocity study was done for reference. The diagnostic confidence of TSE T2W MR sequence was seen to be highest with a sensitivity of 95.31% while it was 81.25% for ultrasonogram. Continuity of the nerve in patients with traumatic neuropathy was seen in 65.7% and 62.86% (22/35) nerves on MRI and ultrasonogram respectively. T1W and T2W MR sequences were seen to be equally effective in establishing the continuity of the nerve. Increase in the calibre/ thickening was seen in 77% of cases on MRI, and 73.8% of cases on USG. Neuroma formation was seen equally on both MR & USG in 60.66%. We consistently found low fractional anisotropy (FA) values at the site of pathology. Ultrasound is a sensitive technique to diagnose peripheral neuropathies and it should be used as a screening modality for a focused MR to be performed later. TSE T2W FS has the highest sensitivity to pick nerve pathology and is comparable to NCS. Amongst the newer sequences, DTI should be done to increase the diagnostic confidence. Copyright © 2017 Elsevier Inc. All rights reserved.
Pasnoor, Mamatha; Dimachkie, Mazen M.; Barohn, Richard J.
Diabetic neuropathies consist of a variety of syndromes resulting from different types of damage to peripheral or cranial nerves. Although distal symmetric polyneuropathy is most common type of diabetic neuropathy, there are many other subtypes of diabetic neuropathies which have been defined since the 1800’s. Included in these descriptions are patients with proximal diabetic, truncal, cranial, median, and ulnar neuropathies. Various theories have been proposed for the pathogenesis of these neuropathies. The treatment of most of these requires tight and stable glycemic control. Spontaneous recovery is seen in most of these conditions with diabetic control Immunotherapies have been tried in some of these conditions but are quite controversial. PMID:23642718
Lewis, R A; Sumner, A J
We compared the electrodiagnostic studies of 40 patients with chronic acquired demyelinative neuropathy and 18 patients with familial demyelinative neuropathy. Patients with acquired neuropathy had differential slowing of conduction velocity when distal latencies were compared with more proximal conduction velocities in the same nerve, when equivalent segments of different nerves were compared, and when dispersion of compound motor action potentials was examined. Conduction block was noted in some patients. Patients with familial disease had uniform conduction slowly of all nerve segments, and conduction block was not seen. Chronic acquired demyelinative neuropathy is characterized by multifocal slowing of nerve conduction, whereas familial demyelinative neuropathy is characterized by uniform conduction slowing.
Christensen, N J; Dejgaard, Anders; Hilsted, J
Forearm venous plasma noradrenalin and dihydroxyphenylglycol (DHPG) concentrations were measured in eight diabetic patients with and eight diabetic patients without neuropathy. Plasma noradrenalin was on average the same in patients with and without neuropathy and correlated to serum creatinine....... Plasma DHPG concentrations were significantly reduced in patients with autonomic neuropathy as compared to patients without neuropathy (P less than 0.05). A low plasma DHPG/noradrenalin ratio in forearm venous blood identified all patients with autonomic neuropathy except one (P less than 0...
This review summarizes the recent genetic advances in hereditary sensorimotor neuropathy also called Charcot-Marie-Tooth disease. The different new genes discovered in 2010 and their underlying phenotypes will be presented.
... National Park Service Notice of Inventory Completion: Western Michigan University, Anthropology Department... Michigan University, Anthropology Department, Kalamazoo, MI. The human remains and associated funerary... anthropologist in the Anthropology Department at Western Michigan University, studied the human remains....
Andary Michael T
Full Text Available Abstract Background Hereditary neuropathy with liability to pressure palsies (HNPP is an autosomal-dominant painless peripheral neuropathy characterized by episodes of repeated focal pressure neuropathies at sites of entrapment/compression, with a considerable variability in the clinical course. Electrodiagnostic and genetic testing are important in the diagnostic evaluation of these patients. Case presentation We report an unusual HNPP phenotype, five compression neuropathies in four nerves in a patient with bilateral hand numbness. A 42-year-old female, presented with acute bilateral paresthesias and weakness in her hands after starting yoga exercises requiring hyperextension of her hands at the wrists. Her presentation was complicated by: a a remote history of acute onset foot drop and subsequent improvement, b previous diagnoses of demyelinating peripheral neuropathy, possibly Charcot-Marie-Tooth disease, and c exposure to leprosy. Electrodiagnostic testing showed 5 separate compression neuropathies in 4 nerves including: severe left and right ulnar neuropathies at the wrist, left and right median neuropathies at the wrist and left ulnar neuropathy at the elbow. There was a mild generalized, primarily demyelinating, peripheral polyneuropathy. Based on the clinical suspicion and electrodiagnostic findings, consistent with profound demyelination in areas of compression, genetic analysis was done which identified a deletion of the PMP-22 gene consistent with HNPP. Conclusion HNPP can present with unusual phenotypes, such as 5 separate mononeuropathies, bilateral ulnar and median neuropathies at the wrists and ulnar neuropathy at the elbow with mild peripheral demyelinating polyneuropathy associated with the PMP-22 gene deletion.
Boezaart, Arnold [GVSU; Edmonson, James [GVSU; Standridge, Charles [GVSU; Pervez, Nahid [GVSU; Desai, Neel [University of Michigan; Williams, Bruce [University of Delaware; Clark, Aaron [GVSU; Zeitler, David [GVSU; Kendall, Scott [GVSU; Biddanda, Bopi [GVSU; Steinman, Alan [GVSU; Klatt, Brian [Michigan State University; Gehring, J. L. [Michigan State University; Walter, K. [Michigan State University; Nordman, Erik E. [GVSU
The purpose of this project was to conduct the first comprehensive offshore wind assessment over Lake Michigan and to advance the body of knowledge needed to support future commercial wind energy development on the Great Lakes. The project involved evaluation and selection of emerging wind measurement technology and the permitting, installation and operation of the first mid-lake wind assessment meteorological (MET) facilities in Michigan’s Great Lakes. In addition, the project provided the first opportunity to deploy and field test floating LIDAR and Laser Wind Sensor (LWS) technology, and important research related equipment key to the sitting and permitting of future offshore wind energy development in accordance with public participation guidelines established by the Michigan Great Lakes Wind Council (GLOW). The project created opportunities for public dialogue and community education about offshore wind resource management and continued the dialogue to foster Great Lake wind resource utilization consistent with the focus of the GLOW Council. The technology proved to be effective, affordable, mobile, and the methods of data measurement accurate. The public benefited from a substantial increase in knowledge of the wind resources over Lake Michigan and gained insights about the potential environmental impacts of offshore wind turbine placements in the future. The unique first ever hub height wind resource assessment using LWS technology over water and development of related research data along with the permitting, sitting, and deployment of the WindSentinel MET buoy has captured public attention and has helped to increase awareness of the potential of future offshore wind energy development on the Great Lakes. Specifically, this project supported the acquisition and operation of a WindSentinel (WS) MET wind assessment buoy, and associated research for 549 days over multiple years at three locations on Lake Michigan. Four research objectives were defined for the
Vasquez, S.; Guidon, Marie; McHugh, E; Lennon, Olive; Grogan, L.; Breathnach, O S
BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, potentially reversible side effect of some chemotherapeutic agents. CIPN is associated with decreased balance, function and quality of life (QoL). This association has to date been under-investigated. AIMS: To profile patients presenting with CIPN using the modified Total Neuropathy Score (mTNS) in this cross-sectional study and to examine the relationship between CIPN (measured by mTNS) and indices of balance, qual...
Boezaart, Arnold [GVSU; Edmonson, James [GVSU; Standridge, Charles [GVSU; Pervez, Nahid [GVSU; Desai, Neel [University of Michigan; Williams, Bruce [University of Delaware; Clark, Aaron [GVSU; Zeitler, David [GVSU; Kendall, Scott [GVSU; Biddanda, Bopi [GVSU; Steinman, Alan [GVSU; Klatt, Brian [Michigan State University; Gehring, J. L. [Michigan State University; Walter, K. [Michigan State University; Nordman, Erik E. [GVSU
The purpose of this project was to conduct the first comprehensive offshore wind assessment over Lake Michigan and to advance the body of knowledge needed to support future commercial wind energy development on the Great Lakes. The project involved evaluation and selection of emerging wind measurement technology and the permitting, installation and operation of the first mid-lake wind assessment meteorological (MET) facilities in Michigan’s Great Lakes. In addition, the project provided the first opportunity to deploy and field test floating LIDAR and Laser Wind Sensor (LWS) technology, and important research related equipment key to the sitting and permitting of future offshore wind energy development in accordance with public participation guidelines established by the Michigan Great Lakes Wind Council (GLOW). The project created opportunities for public dialogue and community education about offshore wind resource management and continued the dialogue to foster Great Lake wind resource utilization consistent with the focus of the GLOW Council. The technology proved to be effective, affordable, mobile, and the methods of data measurement accurate. The public benefited from a substantial increase in knowledge of the wind resources over Lake Michigan and gained insights about the potential environmental impacts of offshore wind turbine placements in the future. The unique first ever hub height wind resource assessment using LWS technology over water and development of related research data along with the permitting, sitting, and deployment of the WindSentinel MET buoy has captured public attention and has helped to increase awareness of the potential of future offshore wind energy development on the Great Lakes. Specifically, this project supported the acquisition and operation of a WindSentinel (WS) MET wind assessment buoy, and associated research for 549 days over multiple years at three locations on Lake Michigan. Four research objectives were defined for the
Hadimani, Mallinath B; Purohit, Meena K; Vanampally, Chandrashaker; Van der Ploeg, Randy; Arballo, Victor; Morrow, Dwane; Frizzi, Katie E; Calcutt, Nigel A; Fernyhough, Paul; Kotra, Lakshmi P
In diabetic patients, an early index of peripheral neuropathy is the slowing of conduction velocity in large myelinated neurons and a lack of understanding of the basic pathogenic mechanisms hindered therapeutics development. Racemic (R/S)-guaifenesin (1) was identified as a potent enhancer of neurite outgrowth using an in vitro screen. Its R-enantiomer (R)-1 carried the most biological activity, whereas the S-enantiomer (S)-1 was inactive. Focused structural variations to (R/S)-1 was conducted to identify potentially essential groups for the neurite outgrowth activity. In vivo therapeutic studies indicated that both (R/S)-1 and (R)-1 partially prevented motor nerve conduction velocity slowing in a mouse model of type 1 diabetes. In vitro microsomal assays suggested that compounds (R)-1 and (S)-1 are not metabolized rapidly, and PAMPA assay indicated moderate permeability through the membrane. Findings revealed here could lead to the development of novel drugs for diabetic neuropathy.
Boulton, Andrew J M; Valensi, Paul; Tesfaye, Solomon
Neuropathies are amongst the most common of the long-term complications of diabetes, affecting up to 50% of patients. Their clinical features vary immensely and patients may present with a wide spectrum of specialties, from neurology to urology, for example, or from cardiology to podiatry. Neuropathies are typically characterized by a progressive loss of nerve fibres which may affect both of the principal divisions of the peripheral nervous system. The epidemiology and natural history of the diabetic neuropathies remain poorly defined. The International Consensus Workshop in Toronto in 2009 arose from the fact that at the moment there are no clear, universally accepted guidelines regarding the definition of diabetic neuropathies. This has resulted in a massive variation in how neuropathy is diagnosed in different centres and countries. A preliminary summary report of the Toronto meeting was published in 2010. The series of papers published in this issue of Diabetes/Metabolism Research and Reviews are the detailed reports that came from each sub-group of this Consensus panel. These reviews cover the problems with definitions and classification of neuropathy, the management of painful neuropathy and then the sub-group of small fibre neuropathies. There are also 3 papers on the autonomic neuropathies, covering cardiovascular autonomic neuropathies, as well as other areas of the autonomic neuropathies including gastrointestinal, urogenital and pseudomotor neuropathies. This series of papers will give the reader detailed information on the diverse aspects of diabetic neuropathies, their measurement and management, and will also assist in the selection of appropriate measures of both autonomic and somatic nerve function in clinical trials. This is clearly work in progress as diagnostic criteria for diabetic neuropathies are likely to evolve with developments in the field.
Full Text Available Trigeminal neuropathy is the most common CNS disorder in Sjogren′s syndrome. It is believed to be caused by vasculitis. Unless this is recognised, a diagnosis of trigeminal neuralgia is often made. The therapeutic response to steroids is unpredictable. There are two subgroups - those with associated collagen disorders and those only with the sicca syndrome.
Schieving, J.H.; Vries, L.B.A. de; Hol, F.A.; Stroink, H.
In 3 young male patients, aged 10, 19 and 21 years respectively, sequential, severe, painless bilateral visual loss occurred. Ophthalmological examination revealed no other abnormalities and this delayed the diagnosis Leber's hereditary optic neuropathy (LHON). LHON is a mitochondrial genetic diseas
Full Text Available Identification and characterization of antigens present at the human peripheral nerve is a great challenge in the field of neuroimmunology. The latest investigations are focused on the understanding of the biology of glycoconjugates present at the peripheral nerve, and their immunological reactivity. Increased titers of antibodies that recognize carbohydrate determinants of glycoconjugates (glycolipids and glycoproteins are associated with distinct neuropathic syndromes. There is considerable cross-reactivity among anti-ganglioside antibodies, resulting from shared oligosaccharide epitopes, possibly explaining the overlap in syndromes observed in many affected patients. Sera from patients with neuropathies (GBS, chronic inflammatory demielynating polyneuropathy - CIDP, multifocal motor neuropathy - MMN, cross-react with glycoproteins isolated from human peripheral nerve and from Campylobacter jejuni O:19. The frequency of occurrence of antibodies against these glycoproteins is different, depending of the type of neuropathy. Identification of the cross-reactive glycoproteins and possible additional auto antigens could be useful in laboratory evaluation of peripheral neuropathies and help to develop a more effective therapeutic approach.
V. A. Bulanova
Full Text Available The clinical case of hereditary neuropathy with liability to pressure palsies (HNPP confirmed the results of DNA diagnostics is described. Clinical and electrophysiological features of the course of HNPP in adolescent is analyzed. Many various illnesses require exclusion in case of the foot extensor paresis.
V. A. Bulanova; D. S. Druzhinin
The clinical case of hereditary neuropathy with liability to pressure palsies (HNPP) confirmed the results of DNA diagnostics is described. Clinical and electrophysiological features of the course of HNPP in adolescent is analyzed. Many various illnesses require exclusion in case of the foot extensor paresis.
Edmonds, M E; Nicolaides, K H; Watkins, P J
Autonomic function was studied in three groups of insulin-dependent diabetic patients. Heart rate changes during deep breathing and on standing were significantly less in 28 patients with a recent history of foot ulceration compared with 40 patients with peripheral neuropathy but without ulceration (p less than 0.001) and 54 patients without neuropathy (p less than 0.001). Sympathetic function was assessed in 36 of these patients from peripheral arterial diastolic flow patterns obtained by Doppler ultrasound measurements and expressed as the pulsatility index (PI). Patients with a history of ulceration (n = 10) showed considerably increased diastolic flow (PI = 4.28 +/- 0.53, mean +/- S.E.M.) compared with 12 neuropathic patients with no history of ulceration (PI = 7.80 +/- 0.68, p less than 0.002) and 14 patients without neuropathy (PI = 9.55 +/- 0.89, p less than 0.002). Severely abnormal autonomic function occurs in association with neuropathic foot ulceration, but patients without ulcers have lesser degrees of autonomic neuropathy, thus a causal relationship has not been established.
The review concentrates on the use of clinical neurophysiology in peripheral nerve disorders covered in the present issue. It is pertinent to distinguish different types of involvement of fibers in diabetic neuropathy, including the involvement of small and large fibers, to outline the diagnostic...
Faber, H.T.; Ru, J.A. de
OBJECTIVE: To describe the clinical characteristics of a 70-year-old female with occipital neuropathy following bone conduction device surgery. DESCRIPTION: A 65-year-old woman underwent bone conduction device placement surgery on the left temporal bone. Postoperatively she progressively developed c
Mohd. Muneer Ahamed
Full Text Available Diabetes is a major public health problem. Diabetes mellitus now affects large number of people in many developing countries than western countries where only two or three percent of the population is affected. With on estimated 33 million people in India alone affected by diabetes. It is a major epidemic of the twentieth century. Diabetes is a chronic disorder, which is associated with obesity, hypertension, advancing age, accumulation of harmful agents in the vascular endothelium causing development of microangiopathies or micro vascular complications. These complications include peripheral neuropathy, nephropathy and retinopathy, which cause early death and increased morbidity. These complications vary in prevalence in different populations depending on various factors such as genetic predisposition and ethnicity. Besides these complications cardiovascular changes are also occurring. Peripheral neuropathy (PN is characterized by pain, numbness, and tingling in the extremities with slow nerve conduction. Up to 50% of all patients with diabetes develop neuropathy and the prevalence of painful neuropathy ranges from 10 to 20% of patients with diabetes. Diabetic nephropathy is characterized by increased urinary protein, loss of renal function, excessive deposition of extracellular matrix proteins in the mesangium, and clear cytoplasm of the proximal tubular epithelial cells due to excessive reabsorbed glycogen. Evaluation of diabetes and its complications is very essential for proper control and prevention of the disease associated complications.
Westfal, Maggie L; Goldstein, Allan M
Neurointestinal diseases are increasingly recognized as causes of significant gastrointestinal morbidity in children. This review highlights the most common pediatric enteric neuropathies and their diagnosis and management, emphasizing insights and discoveries from the most recent literature available. The embryologic and histopathologic causes of enteric neuropathies are varied. They range from congenital aganglionosis in Hirschsprung disease, to autoimmune-mediated loss of neuronal subtypes in esophageal achalasia and Chagas disease, to degenerative neuropathies in some cases of chronic intestinal pseudo-obstruction and gastroparesis. Increased awareness of the clinical presentation and diagnostic evaluation of these conditions is essential as it allows for earlier initiation of treatment and improved outcomes. Most current therapies, which include medical management, neurostimulation, and operative intervention, aim to minimize the symptoms caused by these conditions. The evidence base for many of these treatments in children is poor, and multiinstitutional prospective studies are needed. An innovative therapy on the horizon involves using neuronal stem cell transplantation to treat the underlying disorder by replacing the missing or damaged neurons in these diseases. Although recent advances in basic and clinical neurogastroenterology have significantly improved our awareness and understanding of enteric neuropathies, the efficacy of current treatment approaches is limited. The development of novel therapies, including pharmacologic modulators of neurointestinal function, neurostimulation to enhance gut motility, and neuronal cell-based therapies, is essential to improve the long-term outcomes in children with these disorders.
Irobi, Joy; De Jonghe, Peter; Timmerman, Vincent
Inherited peripheral neuropathies comprise a wide variety of diseases primarily affecting the peripheral nervous system. The best-known peripheral neuropathy is Charcot-Marie-Tooth disease (CMT) described in 1886 by J.-M. Charcot, P. Marie and H.H. Tooth. In 1980, A.E. Harding and P.K. Thomas showed that in a large group of individuals with CMT, several only had motor abnormalities on clinical and electrophysiological examination, whereas sensory abnormalities were absent. This exclusively motor variant of CMT was designated as spinal CMT or hereditary distal spinal muscular atrophy, and included in the distal hereditary motor neuropathies (distal HMN). The distal HMN are clinically and genetically heterogeneous and are subdivided according to the mode of inheritance, age at onset and clinical evolution. Since the introduction of positional cloning, 12 chromosomal loci and seven disease-causing genes have been identified for autosomal dominant and recessive distal HMN. Most of the genes involved have housekeeping functions, as in RNA processing, translation synthesis, glycosylation, stress response, apoptosis, but also axonal trafficking and editing. Functional characterization of the mutations will help to unravel the cellular processes that underlie the specificity of motor neuropathies leading to neurogenic muscular atrophy of distal limb muscles. Here we review the recent progress of the molecular genetics of distal HMN and discuss the genes implicated.
Carlos Eduardo Aparicio
Full Text Available A seven years old, male poodle is examined presenting acute mandible paralysis (dropped jaw, drooling and difficulty for the apprehension and chewing; not evidence of an other alteration of cranial nerves. The muscular biopsy rules out a myositisof masticatory muscles. The disorder is resolved completely in 3 weeks confirming diagnosis of idiopathic trigeminal neuropathy.
Reeves, Howard W.; Seelbach, Paul W.; Nicholas, James R.; Hamilton, David A.; Potter, Kenneth W.; Frevert, Donald K.
In 2008, the State of Michigan enacted legislation requiring that new or increased high-capacity withdrawals (greater than 100,000 gallons per day) from either surface water or groundwater be reviewed to prevent Adverse Resource Impacts (ARI). Science- based guidance was sought in defining how groundwater or surface-water withdrawals affect streamflow and in quantifying the relation between reduced streamflow and changes in stream ecology. The implementation of the legislation led to a risk-based system based on a gradient of risk, ecological response curves, and estimation of groundwater-surface water interaction. All Michigan streams are included in the legislation, and, accordingly, all Michigan streams were classified into management types defined by size of watershed, stream-water temperature, and predicted fish assemblages. Different streamflow removal percentages define risk-based thresholds allowed for each type. These removal percentages were informed by ecological response curves of characteristic fish populations and finalized through a legislative workgroup process. The assessment process includes an on-line screening tool that may be used to evaluate new or increased withdrawals against the risk-based zones and allows withdrawals that are not likely to cause an ARI to proceed to water-use registration. The system is designed to consider cumulative impacts of high-capacity withdrawals and to promote user involvement in water resource management by the establishment of water-user committees as cumulative withdrawals indicate greater potential for ARI in the watershed.
Davidson, G L
The hereditary sensory and autonomic neuropathies (HSAN, also known as the hereditary sensory neuropathies) are a clinically and genetically heterogeneous group of disorders, characterised by a progressive sensory neuropathy often complicated by ulcers and amputations, with variable motor and autonomic involvement. To date, mutations in twelve genes have been identified as causing HSAN. To study the frequency of mutations in these genes and the associated phenotypes, we screened 140 index patients in our inherited neuropathy cohort with a clinical diagnosis of HSAN for mutations in the coding regions of SPTLC1, RAB7, WNK1\\/HSN2, FAM134B, NTRK1 (TRKA) and NGFB. We identified 25 index patients with mutations in six genes associated with HSAN (SPTLC1, RAB7, WNK1\\/HSN2, FAM134B, NTRK1 and NGFB); 20 of which appear to be pathogenic giving an overall mutation frequency of 14.3%. Mutations in the known genes for HSAN are rare suggesting that further HSAN genes are yet to be identified. The p.Cys133Trp mutation in SPTLC1 is the most common cause of HSAN in the UK population and should be screened first in all patients with sporadic or autosomal dominant HSAN.
... Zone 140--Flint, Michigan; Application for Subzone; Hemlock Semiconductor Corporation (Polysilicon... facility of Hemlock Semiconductor Corporation (HSC), located in Hemlock, Michigan. The application...
Veil, J. A.; Elcock, D.; Gasper, J. R.; Environmental Science Division
BP Products North America Inc. (BP) owns and operates a petroleum refinery located on approximately 1,700 acres in Whiting, East Chicago, and Hammond, Indiana, near the southern tip of Lake Michigan. BP provided funding to Purdue University-Calumet Water Institute (Purdue) and Argonne National Laboratory (Argonne) to conduct studies related to wastewater treatment and discharges. Purdue and Argonne are working jointly to identify and characterize technologies that BP could use to meet the previous discharge permit limits for total suspended solids (TSS) and ammonia after refinery modernization. In addition to the technology characterization work, Argonne conducted a separate project task, which is the subject of this report. In Phase I of a two-part study, Argonne estimated the current levels of discharge to southern Lake Michigan from significant point and nonpoint sources in Illinois, Indiana, and portions of Michigan. The study does not consider all of the chemicals that are discharged. Rather, it is narrowly focused on a selected group of pollutants, referred to as the 'target pollutants'. These include: TSS, ammonia, total and hexavalent chromium, mercury, vanadium, and selenium. In Phase II of the study, Argonne will expand the analysis to cover the entire Lake Michigan drainage basin.
Landowski, Lila M; Dyck, P James B; Engelstad, JaNean; Taylor, Bruce V
Peripheral neuropathies (PNs) are injuries or diseases of the nerves which arise from varied aetiology, including metabolic disease, trauma and drug toxicity. The clinical presentation depends on the type of neuropathy, and may include the loss of motor, sensory and autonomic functions, or development of debilitating neuropathic pain distal to the injury site. It can be challenging to identify the aetiology of PNs, as the clinical syndromes are often indistinct. However, the mechanisms that underlie pathological changes in peripheral neuropathy are fundamentally different, depending on the trigger. This review focuses on the axonopathy observed in two frequently encountered forms of peripheral neuropathy, diabetic neuropathy and chemotherapy-induced neuropathy. A key manifestation of axonopathy in PN is the degeneration of terminal arbors of peripheral nerves, resulting in a loss of epidermal nerve fibres and inappropriate termination of nerve endings. Many symptoms of PN arise from aberrant termination of nerve endings, and the underlying axonopathy may be non-reversible, as nerve regeneration after injury and disease is often poor, absent, or aberrant. Directed guidance of terminal arbors back into the epidermis is therefore a suggested approach to treat peripheral neuropathy. This review will outline potential strategies to enhance and guide axonal regeneration and reinnervation in the skin. Using diabetic neuropathy and chemotherapy-induced neuropathy as specific examples, this review examines the setbacks encountered with the translation of growth factors into therapeutics for human neuropathy, and suggests a number of approaches for topical drug delivery.
Boso, F; Ruggero, S; Giannotta, C; Benedetti, L; Marfia, G A; Ermani, M; Campagnolo, M; Salvalaggio, A; Gallia, F; De Michelis, C; Visentin, A; Bianco, M; Ruiz, M; Mataluni, G; Nobile-Orazio, E; Briani, C
Anti-sulfatide antibodies have been observed in heterogeneous neuropathies and their clinical relevance is still controversial. Whether the combination of sulfatide with galactocerebroside would increase sensitivity or specificity of enzyme-linked immunosorbent assay testing compared to sulfatide alone was assessed. Immunoglobulin M (IgM) antibodies to sulfatides, galactocerebroside and combined sulfatide and galactocerebroside (Sulf/GalC) were measured in 229 neuropathy patients, including 73 with IgM paraproteinemic neuropathy [62 with anti-myelin-associated glycoprotein (anti-MAG) antibody] and 156 with other neuropathies. Results from 27 patients with IgM monoclonal gammopathy without neuropathy and 28 healthy subjects served as control. Thirty-three patients showed increased titers of anti-sulfatide antibodies, 28 of whom had an IgM paraproteinemic neuropathy (P neuropathies), who had no reactivity to the individual glycolipids. Amongst the 11 subjects with IgM paraproteinemic neuropathy who were negative for anti-MAG antibodies, only two were reactive to sulfatide, whilst six (55%) were found to be positive when tested against the combination of sulfatide and galactocerebroside. Testing for both sulfatide and galactocerebroside in IgM paraproteinemic neuropathies seems to increase the sensitivity compared to anti-sulfatide antibodies alone (49% and 39%, respectively, with a slightly reduced specificity, from 97% to 87%), helping the characterization of otherwise undefined neuropathy that could benefit from immunomodulatory therapy. © 2017 EAN.
Dallo, Florence J.; Schwartz, Kendra; Ruterbusch, Julie J.; Booza, Jason; Williams, David R.
The objectives of this study were to: (1) calculate age-specific and age-adjusted cause-specific mortality rates for Arab Americans; and (2) compare these rates with those for blacks and whites. Mortality rates were estimated using Michigan death certificate data, an Arab surname and first name list, and 2000 U.S. Census data. Age-specific rates, age-adjusted all-cause and cause-specific rates were calculated. Arab Americans (75+) had higher mortality rates than whites and blacks. Among men, ...
Scenario forecasts for total PCBs in Lake Michigan (LM) lake trout were conducted using the linked LM2-Toxics and LM Food Chain models, supported by a suite of additional LM models. Efforts were conducted under the Lake Michigan Mass Balance Study and the post audit represents th...
Kearney, C. Philip
Examines Michigan's attempt to abolish the school property tax and implications for New York State policymakers. Michigan substantially reduced the local property tax for local school operations, adopted a permanent set of tax and revenue limits, and devised a problematic assessment cap. Totally eliminating the local school property tax may be…
Brunet, P; Binet, J L; de Saxce, H; Gray, F; De Baecque, C; Raphael, M; Lyon-Caen, O
Four cases of angioimmunoblastic lymphadenopathy associated to peripheral neuropathy are described. The neuropathy was mixed, sensory and motor, more or less extensive, always asymetrical. In two cases, the clinical symptomatology and the clinical course were very peculiar, characterized by sensory disorders of a precise topography, circumscribed and sometimes suspended and by a relapsing and remitting course. In the third case, the neurological signs were acute and rapidly extensive with mandatory respiratory assistance. In this case, death occurred after a few weeks and the exact diagnosis was only attained at post-mortem examination. In the fourth case the neuropathy was very painful but the course was slow. In all four cases marked and extensive pain was present prior to the neurological disorders. Electrophysiological abnormalities were a constant feature with a marked slowing down of nerve conduction velocity. CSF was normal at the beginning in one case but was otherwise markedly pathological with an increased number of cells due to a large number of lymphocytes ranging from 6 to 40 cells while protein ranged from 60 to 160 mg per 100 ml. Nerve and muscle biopsies were non specific, i.e. neurogenous muscular atrophy and demyelination, except in case n. 4 where specific angioimmunoblastic lymphadenopathy infiltrates were present both in nerve and muscle. In cases 1 and 3 a non specific lymphohistiocytic infiltrate was present in spinal roots and meninges. Corticotherapy was used and efficient in two cases. These data are compared with a review of the literature. Since 1976, 7 cases of angioimmunoblastic lymphadenopathy associated to peripheral neuropathy have been reported. Clinical, electrophysiological and biological features are similar. Only one case underwent a post mortem examination of the central nervous system: a non specific lymphocytic infiltration in the spinal roots and meninges was mentioned. The role of the dysproteinemia associated with the AIL
Sacre, J W; Jellis, C L; Coombes, J S; Marwick, T H
Poor prognosis associated with blunted post-exercise heart-rate recovery may reflect autonomic dysfunction. This study sought the accuracy of post-exercise heart-rate recovery in the diagnosis of cardiac autonomic neuropathy, which represents a serious, but often unrecognized complication of Type 2 diabetes. Clinical assessment of cardiac autonomic neuropathy and maximal treadmill exercise testing for heart-rate recovery were performed in 135 patients with Type 2 diabetes and negative exercise echocardiograms. Cardiac autonomic neuropathy was defined by abnormalities in ≥ 2 of 7 autonomic function markers, including four cardiac reflex tests and three indices of short-term (5-min) heart-rate variability. Heart-rate recovery was defined at 1-, 2- and 3-min post-exercise. Patients with cardiac autonomic neuropathy (n = 27; 20%) had lower heart-rate recovery at 1-, 2- and 3-min post-exercise (P Heart-rate recovery demonstrated univariate associations with autonomic function markers (r-values 0.20-0.46, P heart-rate recovery parameters (range 0.80-0.83, P heart-rate recovery at 1-, 2- and 3-min post-exercise were ≤ 28 beats/min (sensitivity 93%, specificity 69%), ≤ 50 beats/min (sensitivity 96%, specificity 63%) and ≤ 52 beats/min (sensitivity 70%, specificity 84%), respectively. These criteria predicted cardiac autonomic neuropathy independently of relevant clinical and exercise test information (adjusted odds ratios 7-28, P exercise heart-rate recovery provides an accurate diagnostic test for cardiac autonomic neuropathy in Type 2 diabetes. The high sensitivity and modest specificity suggests heart-rate recovery may be useful to screen for patients requiring clinical autonomic evaluation. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.
Brenneise, Harvey R.
The Michigan Community Health Electronic Library (MCHEL) serves the public health and other community health workers in Michigan. It is committed to desktop delivery of the best health information to its primary clientele, with as much as possible in digital full-text form. It collaborates with other libraries in the state to make this possible.…
Brenneise, Harvey R.
The Michigan Community Health Electronic Library (MCHEL) serves the public health and other community health workers in Michigan. It is committed to desktop delivery of the best health information to its primary clientele, with as much as possible in digital full-text form. It collaborates with other libraries in the state to make this possible.…
Panosyan, Francis B; Kirk, Callyn A; Marking, Devon; Reilly, Mary M; Scherer, Steven S; Shy, Michael E; Herrmann, David N
This study evaluates carpal tunnel syndrome (CTS) symptom severity, functional status, and outcome of CTS therapies in patients with inherited neuropathies. Validated questionnaires were used to compare symptom severity and functional status in patients with and without a diagnosis of CTS and a diagnosis of an inherited neuropathy. 309 patients with inherited neuropathies participated in this study. The CTS symptom severity score (SSS) was found to be the most useful tool in assessing CTS severity in patients with inherited neuropathy. Splint therapy and surgery were associated with significant improvement in carpal tunnel symptoms as measured through the SSS. This study provides insight into the assessment of CTS symptom severity and patient-reported outcomes to CTS therapy in individuals with inherited neuropathies. The SSS appears useful for evaluation of CTS symptoms and patient-reported outcomes following CTS interventions in individuals with inherited neuropathies. Muscle Nerve, 2017. © 2017 Wiley Periodicals, Inc.
Jeffcoate, W J; Rasmussen, Lars Melholt; Hofbauer, L C
Calcification of the media of arterial walls is common in diabetes and is particularly associated with distal symmetrical neuropathy. Arterial calcification also complicates chronic kidney disease and is an independent risk factor for cardiovascular and all-cause mortality. The term calcification...... factor linked to the development of arterial calcification is distal symmetrical neuropathy; indeed, it has been suggested that neuropathy explains the distal distribution of arterial calcification in diabetes. It has also been suggested that the link with neuropathy results from loss of neuropeptides......, such as calcitonin gene-related peptide, which are inherently protective. The association between distal symmetrical neuropathy and calcification of the arterial wall highlights the fact that neuropathy may be an independent risk factor for cardiovascular mortality....
Neuropathy associated with Diabetes is increasing at epidemic rates throughout the world. Traditionally, this neuropathy causes loss of protective sensation leading to ulceration, infection , and amputation. Even with good glycemic control, this neuropathy is still considered progressive and irrever
Şefik Evren Erdener
Full Text Available Multifocal acquired demyelinating sensory and motor (MADSAM neuropathy is characterized by asymmetric multifocal motor and sensory loss and conduction blocks in peripheral nerves. Peripheral demyelinating diseases may be accompanied by demyelination in central nervous system (CNS. In this report, a MADSAM patient with a solitary tumefactive demyelinating lesion in brain is presented. Neuroimaging due to a visual field defect revealed a right parietooccipital lesion, which was initially misdiagnosed as a tumor. Pathological examination showed that it was demyelinating in nature. Peripheral nervous symptoms of the patient developed two years later and she was then diagnosed with MADSAM. There was prominent clinical and electrophysiological response to steroid treatment. Tumefactive brain involvement was not previously reported for MADSAM neuropathy, although it was documented in a single case with typical chronic inflammatory demyelinating polyneuropathy (CIDP. CNS involvement should therefore be considered in MADSAM patients.
Martinez, Alberto R M; Faber, Ingrid; Nucci, Anamarli; Appenzeller, Simone; França, Marcondes C
Systemic manifestations are frequent in autoimmune rheumatic diseases and include peripheral nervous system damage. Neuron cell body, axons and myelin sheath may all be affected in this context. This involvement results in severe and sometimes disabling symptoms. Sensory, motor and autonomic features may be present in different patterns that emerge as peculiar clinical pictures. Prompt recognition of these neuropathies is pivotal to guide treatment and reduce the risks of long term disability. In this review, we aim to describe the main immune-mediated neuropathies associated to rheumatic diseases: sensory neuronopathies, multiple mononeuropathies and chronic inflammatory demyelinating polyradiculoneuropathy, with an emphasis on clinical features and therapeutic options. Copyright © 2017 Elsevier B.V. All rights reserved.
Maria Eugenia Niño Mantilla
Full Text Available the dysfunction of the autonomic nervous system is a serious problem in diabetic patients. The cardiovacular autonomic neuropathy is the most important autonomic dysfuntion for it´s implication in the increasesof the mortality rate in diabetis patients. tis ethiopatogenesis is the result of a multifactorial process caused by chronic hyperglycemia, ending up in damage of the autonomic fibers thet innervate the heart and blood vessels, leading to dysfuntional hearth rate control and abnormal vascular dynamics. the associated clinical manifestations include orthotatic hypotension, excecise intolerance, intraoperative cardiovascular liability and silent myocardial ischemia. Being important its recognition, quantitative test to evaluate the cardiovascular funtion, to value its evolution and the effects of the treatment ahould be done, being the most used, the hearth rate response to standing test, and teh valsalva maneuver. the handling of this entity is done improving control of glucose blood levels its the most effective way to prevent the cardiovascular autonomic neuropathy in the diabetic patients.
Painful diabetic neuropathy is a model for the investigation of drug’s efficacy in neuropathic pain. Diabetes, through multiple pathophysiological mechanisms causes several painful neuropathies. In this paper two clinical cases of painful diabetic neuropathic conditions are described and clinical and neurophysiological criteria to make the correct diagnosis are examined. Diabetes causes different painful diabetic neuropathies, at times even in a single patient. Different types of pai...
Pasnoor, Mamatha; Nascimento, Osvaldo J M; Trivedi, Jaya; Wolfe, Gil I; Nations, Sharon; Herbelin, Laura; de Freitas, M G; Quintanilha, Giseli; Khan, Saud; Dimachkie, Mazen; Barohn, Richard
Peripheral neuropathy is a common neurological disorder. There may be important differences and similarities in the diagnosis of peripheral neuropathy between North America (NA) and South America (SA). Neuromuscular databases were searched for neuropathy diagnosis at two North American sites, University of Kansas Medical Center and University of Texas Southwestern Medical Center, and one South American site, Federal Fluminense University in Brazil. All patients were included into one of the six major categories: immune-mediated, diabetic, hereditary, infectious/inflammatory, systemic/metabolic/toxic (not diabetic) and cryptogenic. A comparison of the number of patients in each category was made between North America and South America databases. Total number of cases in North America was 1090 and in South America was 1034 [immune-mediated: NA 215 (19.7%), SA 191 (18%); diabetic: NA 148 (13.5%), SA 236 (23%); hereditary: NA 292 (26.7%), SA 103 (10%); infectious/inflammatory: NA 53 (4.8%), SA 141 (14%); systemic/metabolic/toxic: NA 71 (6.5%), SA 124 (12%); cryptogenic: NA 311 (28.5%), SA 239 (23%)]. Some specific neuropathy comparisons were hereditary neuropathies [Charcot-Marie-Tooth (CMT) cases] in NA 246/292 (84.2%) and SA 60/103 (58%); familial amyloid neuropathy in SA 31/103 (30%) and none in NA. Among infectious neuropathies, cases of human T-lymphotropic virus type 1 (HTLV-1) neuropathy in SA were 36/141(25%), Chagas disease in SA were 13/141(9%) and none for either in NA; cases of neuropathy due to leprosy in NA were 26/53 (49%) and in SA were 39/141(28%). South American tertiary care centers are more likely to see patients with infectious, diabetic and hereditary disorders such as familial amyloid neuropathies. North American tertiary centers are more likely to see patients with CMT. Immune neuropathies and cryptogenic neuropathies were seen equally in North America and South America.
Small, Juan E. [Massachusetts General Hospital and Harvard Medical School, Department of Radiology, Boston, MA (United States); Gonzalez, Guido E. [Massachusetts Eye and Ear Infirmary and Harvard Medical School, Department of Radiology, Boston, MA (United States); Clinica Alemana de Santiago, Departmento de Imagenes, Santiago (Chile); Nagao, Karina E.; Walton, David S. [Massachusetts Eye and Ear Infirmary and Harvard Medical School, Department of Ophthalmology, Boston, MA (United States); Caruso, Paul A. [Massachusetts Eye and Ear Infirmary and Harvard Medical School, Department of Radiology, Boston, MA (United States)
Pyruvate dehydrogenase (PDH) deficiency is a genetic disorder of mitochondrial metabolism. The clinical manifestations range from severe neonatal lactic acidosis to chronic neurodegeneration. Optic neuropathy is an uncommon clinical sequela and the imaging findings of optic neuropathy in these patients have not previously been described. We present a patient with PDH deficiency with bilateral decreased vision in whom MRI demonstrated bilateral optic neuropathy and chiasmopathy. (orig.)
Full Text Available Background: Ulnar nerve entrapment at the elbow is the second most common upper extremity nerve involvement after median nerve involvement at the wrist or carpal tunnel syndrome (CTS considering the frequency of occurrence in the upper limb with variable causes. Hemodialysis, because of elbow positioning during dialysis, upper extremity vascular-access, and underlying disease is one cause of ulnar entrapment. This study considers evaluating the effect of elbow positioning on ulnar involvement prevalence during dialysis. Materials and Methods: This cross-sectional study started in June 2011 and completed in December 2011. The patients receiving dialysis with at least one symptom or sign of ulnar nerve involvement underwent nerve conduction studies. Electromyography testing (EMG performed to confirm the ulnar neuropathy. To review the ulnar nerve, patients must be in supine position with arm in 90° abduction and elbow in 135° flexion. We stimulated the ulnar nerve at three different points, including 6 cm above and 4 cm below the elbow and over the wrist. According to the electrophysiological data, the intensity of nerve entrapment and possibility of associated polyneuropathy determined. Results: Clinically and electrodiagnostically, evidence confirmed that ulnar neuropathy was present in 11 (27.5% of 40 hemodialysis patients and in 10 (25% of 40 peritoneal patients (P value: 0.83. Also, the prevalence of median neuropathy in hemodialysis and peritoneal dialysis patients was 14 (35% and 10 (25%, respectively (P value: 0.33. Conclusion: The frequency of median and ulnar neuropathy in hemodialysis patients is more than peritoneal dialysis, but this different is not significant. In addition, comparing sitting position with prolonged elbow flexion and supine position with elbow extension during hemodialysis, recommended doing hemodialysis in later position with using an elbow pad.
Abnormal neuronal calcium (Ca2+) homeostasis has been implicated in numerous diseases of the nervous system. The pathogenesis of two increasingly common disorders of the peripheral nervous system, namely neuropathic pain and diabetic polyneuropathy, has been associated with aberrant Ca2+ channel expression and function. Here we review the current state of knowledge regarding the role of Ca2+ dyshomeostasis and associated mitochondrial dysfunction in painful and diabetic neuropathies. The cent...
Kim, Jee-Eun; Park, Su-Yeon; Sinn, Dong In; Kim, Sung-Min; Hong, Yoon-Ho; Park, Kyung Seok; Sung, Jung-Joon; Lee, Kwang-Woo
Background Livedoid vasculitis is a chronic dermatological problem with an unclear etiology. Clinical findings are petechiae with painful ulcers in both lower extremities, which heal to become hyperpigmented and porcelain-white satellite lesions. There are only a few reported cases of livedoid vasculitis presenting in combination with peripheral neuropathy. Case Report We report the first case of a Korean patient presenting with mononeuritis multiplex combined with livedoid vasculitis, which ...
Kerasnoudis, Antonios; Tsivgoulis, Georgios
Peripheral neuropathies are one of the most common reasons for seeking neurological care in everyday practice. Electrophysiological studies remain fundamental for the diagnosis and etiological classification of peripheral nerve impairment. The recent technological development though of high resolution ultrasound has allowed the clinician to obtain detailed structural images of peripheral nerves. Nerve ultrasound mainly focuses on the evaluation of the cross sectional area, cross sectional area variability along the anatomical course, echogenity, vascularity and mobility of the peripheral nerves. An increase of the cross sectional area, hypervascularity, disturbed fascicular echostructure and reduced nerve mobility are some of the most common findings of entrapments neuropathies, such as the carpal or cubital tunnel syndrome. Both the cross-sectional area increase and the hypervascularity detected with the Doppler technique seem to correlate significantly with the clinical and electrophysiological severity of the later mononeuropathies. Significantly greater cross sectional area values of the clinically affected cervical nerve root are often detected in cases of cervical radiculopathy. In such cases, the ultrasound findings seem also to correlate significantly with disease duration. On the other hand, multifocal cross sectional area enlargement of cervical roots and/or peripheral nerves is often documented in cases of immune-mediated neuropathies. None of the later pathological ultrasound findings seem to correlate significantly with the electrophysiological parameters or the functional disability. The aim of this review is to provide a timely update on the role of neuromuscular ultrasound in the diagnostic of the most common entrapment and immune-mediated peripheral neuropathies in clinical practice. Copyright © 2015 by the American Society of Neuroimaging.
Xiao, Xueshan; Li, Shiqiang
Leber hereditary optic neuropathy (LHON) and dominant optic atrophy (DOA), the most common forms of hereditary optic neuropathy, are easily confused, and it is difficult to distinguish one from the other in the clinic, especially in young children. The present study was designed to survey the mutation spectrum of common pathogenic genes (OPA1, OPA3 and mtDNA genes) and to analyze the genotype-phenotype characteristics of Chinese patients with suspected childhood-onset hereditary optic neuropathy. Genomic DNA and clinical data were collected from 304 unrelated Chinese probands with suspected hereditary optic neuropathy with an age of onset below 14 years. Sanger sequencing was used to screen variants in the coding and adjacent regions of OPA1, OPA3 and the three primary LHON-related mutation sites in mitochondrial DNA (mtDNA) (m.3460G>A, m.11778G>A and m.14484T>C). All patients underwent a complete ophthalmic examination and were compared with age-matched controls. We identified 89/304 (29.3%) primary mtDNA mutations related to LHON in 304 probands, including 76 mutations at m.11778 (76/89, 85.4% of all mtDNA mutations), four at m.3460 (4/89, 4.5%) and nine at m.14484 (9/89, 10.1%). This result was similar to the mutation frequency among Chinese patients with LHON of any age. Screening of OPA1 revealed 23 pathogenic variants, including 11 novel and 12 known pathogenic mutations. This study expanded the OPA1 mutation spectrum, and our results showed that OPA1 mutation is another common cause of childhood-onset hereditary optic neuropathy in Chinese pediatric patients, especially those with disease onset during preschool age. PMID:28081242
Tey, S; Ahmad-Annuar, A; Drew, A P; Shahrizaila, N; Nicholson, G A; Kennerson, M L
The cytoplasmic dynein-dynactin genes are attractive candidates for neurodegenerative disorders given their functional role in retrograde transport along neurons. The cytoplasmic dynein heavy chain (DYNC1H1) gene has been implicated in various neurodegenerative disorders, and dynactin 1 (DCTN1) genes have been implicated in a wide spectrum of disorders including motor neuron disease, Parkinson's disease, spinobulbar muscular atrophy and hereditary spastic paraplegia. However, the involvement of other dynactin genes with inherited peripheral neuropathies (IPN) namely, hereditary sensory neuropathy, hereditary motor neuropathy and Charcot-Marie-Tooth disease is under reported. We screened eight genes; DCTN1-6 and ACTR1A and ACTR1B in 136 IPN patients using whole-exome sequencing and high-resolution melt (HRM) analysis. Eight non-synonymous variants (including one novel variant) and three synonymous variants were identified. Four variants have been reported previously in other studies, however segregation analysis within family members excluded them from causing IPN in these families. No variants of disease significance were identified in this study suggesting the dynactin genes are unlikely to be a common cause of IPNs. However, with the ease of querying gene variants from exome data, these genes remain worthwhile candidates to assess unsolved IPN families for variants that may affect the function of the proteins.
Full Text Available Cherise Meyerson, Greg Van Stavern, Collin McClelland Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, MO, USA Abstract: Leber hereditary optic neuropathy (LHON is one of the most common inherited optic neuropathies causing bilateral central vision loss. The disorder results from point mutations in mitochondrial DNA and subsequent mitochondrial dysfunction. The primary cell type that is lost in LHON is the retinal ganglion cell, which is highly susceptible to disrupted ATP production and oxidative stress. Inheritance of LHON follows that of mitochondrial genetics, and it has a highly variable clinical phenotype, as other genetic and environmental factors also play a role. Although LHON usually presents with isolated vision loss, some patients suffer other neurological sequelae. For ill-defined reasons, male LHON mutation carriers are more affected than females. Most LHON patients remain legally blind, but a small proportion can experience spontaneous partial recovery, often within the first year of symptom onset. Unfortunately, at this time there are no established curative interventions and treatment is largely supportive. Patients should be offered low vision services and counseled on mitigating risk factors for additional vision loss, such as smoking and consuming alcohol. Encouraging treatments currently undergoing investigation includes ubiquinone analogs, such as idebenone, as well as gene therapy and stem cells to restore ATP synthesis and provide neuroprotection to surviving retinal ganglion cells. Keywords: Leber hereditary optic neuropathy, mitochondria, neuro-ophthalmology, mitochondrial DNA
Chiara eLa Morgia
Full Text Available Hereditary optic neuropathies are diseases of the optic nerve. The most common are mitochondrial hereditary optic neuropathies, i.e. the maternally inherited Leber’s Hereditary Optic Neuropathy (LHON and Dominant Optic Atrophy (DOA. They both share a mitochondrial pathogenesis that leads to the selective loss of retinal ganglion cells and axons, in particular of the papillo-macular bundle. Typically, LHON is an acute/subacute loss of central vision associated with impairment of color vision and swelling of retinal nerve fibers followed by optic atrophy. DOA, instead, is characterized by a childhood-onset and slowly progressive loss of central vision, worsening over the years, leading to optic atrophy. The diagnostic workup includes neuro-ophthalmologic evaluation and genetic testing of the three most common mitochondrial DNA mutations affecting complex I (11778/ND4, 3460/ND1 and 14484/ND6 for LHON and sequencing of the nuclear gene OPA1 for DOA. Therapeutic strategies are limited including agents that bypass the complex I defect and exert an antioxidant effect (idebenone. Further strategies are aimed at stimulating compensatory mitochondrial biogenesis. Gene therapy is also a promising venue that still needs to be validated.
Qi Zhe Ngoo; Li Min Evelyn Tai; Wan Hazabbah Wan Hitam; John Tharakan
We reported a case of cryptococcal meningitis presenting with bilateral optic neuropathy in an immunocompetent patient. A 64-year-old Malay gentleman with no medical comorbidities presented with acute bilateral blurring of vision for a week, which was associated with generalised throbbing headache and low grade fever. He also had som-nolence and altered consciousness. Visual acuity in both eyes was no perception of light with poor pupillary reflexes. Extraocular muscle movements were normal. Anterior segments were unremarkable bilaterally. Fundoscopy revealed bilateral optic disc swelling. CT scan of the brain showed multifocal infarct, but no meningeal enhancement or mass. Cerebrospinal fluid opening pressure was normal, while its culture grew Cryptococcus neoformans. A diagnosis of cryptococcal meningitis with bilateral optic neuropathy was made. Patient was treated with a six-week course of intravenous flu-conazole and started concomitantly on a fortnight's course of intravenous amphotericin B. After that, his general condition improved, but there was still no improvement in his visual acuity. On reviewing at two months post-initiation of treatment, fundi showed bilateral optic atrophy. Bilateral optic neuropathy secondary to cryptococcal meningitis was rare. The prognosis was guarded due to the sequelae of optic atrophy. Anti-fungal medication alone may not be sufficient to manage this condition. However, evidence for other treatment modalities is still lacking and further clinical studies are required.
La Morgia, Chiara; Carbonelli, Michele; Barboni, Piero; Sadun, Alfredo Arrigo; Carelli, Valerio
Hereditary optic neuropathies are diseases affecting the optic nerve. The most common are mitochondrial hereditary optic neuropathies, i.e., the maternally inherited Leber’s hereditary optic neuropathy (LHON) and dominant optic atrophy (DOA). They both share a mitochondrial pathogenesis that leads to the selective loss of retinal ganglion cells and axons, in particular of the papillo-macular bundle. Typically, LHON is characterized by an acute/subacute loss of central vision associated with impairment of color vision and swelling of retinal nerve fibers followed by optic atrophy. DOA, instead, is characterized by a childhood-onset and slowly progressive loss of central vision, worsening over the years, leading to optic atrophy. The diagnostic workup includes neuro-ophthalmologic evaluation and genetic testing of the three most common mitochondrial DNA mutations affecting complex I (11778/ND4, 3460/ND1, and 14484/ND6) for LHON and sequencing of the nuclear gene OPA1 for DOA. Therapeutic strategies are still limited including agents that bypass the complex I defect and exert an antioxidant effect (idebenone). Further strategies are aimed at stimulating compensatory mitochondrial biogenesis. Gene therapy is also a promising avenue that still needs to be validated. PMID:25132831
Cassereau, J; Codron, P; Funalot, B
Mitochondrial disorders (MIDs) are frequently responsible for neuropathies with variable severity. Mitochondrial diseases causing peripheral neuropathies (PNP) may be due to mutations of mitochondrial DNA (mtDNA), as is the case in MERRF and MELAS syndromes, or to mutations of nuclear genes. Secondary abnormalities of mtDNA (such as multiple deletions of muscle mtDNA) may result from mitochondrial disorders due to mutations in nuclear genes involved in mtDNA maintenance. This is the case in several syndromes caused by impaired mtDNA maintenance, such as Sensory Ataxic Neuropathy, Dysarthria and Ophthalmoplegia (SANDO) due to recessive mutations in the POLG gene, which encodes the catalytic subunit of mtDNA polymerase (DNA polymerase gamma), or Mitochondrial Neuro-Gastro-Intestinal Encephalomyopathy (MNGIE), due to recessive mutations in the TYMP gene, which encodes thymidine phosphorylase. The last years have seen a growing list of evidence demonstrating that mitochondrial bioenergetics and dynamics might be dysfunctional in axonal Charcot-Marie-Tooth disease (CMT2), and these mechanisms might present a common link between dissimilar CMT2-causing genes. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
La Morgia, Chiara; Carbonelli, Michele; Barboni, Piero; Sadun, Alfredo Arrigo; Carelli, Valerio
Hereditary optic neuropathies are diseases affecting the optic nerve. The most common are mitochondrial hereditary optic neuropathies, i.e., the maternally inherited Leber's hereditary optic neuropathy (LHON) and dominant optic atrophy (DOA). They both share a mitochondrial pathogenesis that leads to the selective loss of retinal ganglion cells and axons, in particular of the papillo-macular bundle. Typically, LHON is characterized by an acute/subacute loss of central vision associated with impairment of color vision and swelling of retinal nerve fibers followed by optic atrophy. DOA, instead, is characterized by a childhood-onset and slowly progressive loss of central vision, worsening over the years, leading to optic atrophy. The diagnostic workup includes neuro-ophthalmologic evaluation and genetic testing of the three most common mitochondrial DNA mutations affecting complex I (11778/ND4, 3460/ND1, and 14484/ND6) for LHON and sequencing of the nuclear gene OPA1 for DOA. Therapeutic strategies are still limited including agents that bypass the complex I defect and exert an antioxidant effect (idebenone). Further strategies are aimed at stimulating compensatory mitochondrial biogenesis. Gene therapy is also a promising avenue that still needs to be validated.
Pasnoor, Mamatha; Dimachkie, Mazen M; Barohn, Richard J
Diabetic neuropathies consist of a variety of syndromes resulting from different types of damage to peripheral or cranial nerves. Although distal symmetric polyneuropathy is the most common type of diabetic neuropathy, many other subtypes have been defined since the 1800s, including proximal diabetic, truncal, cranial, median, and ulnar neuropathies. Various theories have been proposed for the pathogenesis of these neuropathies. The treatment of most requires tight and stable glycemic control. Spontaneous recovery is seen in most of these conditions with diabetic control. Immunotherapies have been tried in some of these conditions however are controversial.
Full Text Available Painful diabetic neuropathy is a model for the investigation of drug’s efficacy in neuropathic pain. Diabetes, through multiple pathophysiological mechanisms causes several painful neuropathies. In this paper two clinical cases of painful diabetic neuropathic conditions are described and clinical and neurophysiological criteria to make the correct diagnosis are examined. Diabetes causes different painful diabetic neuropathies, at times even in a single patient. Different types of pains may originate from different nerve injuries, and harbour different pathophysiological mechanisms. A comprehensive and accurate evaluation of clinical and neurophysiological abnormalities in painful diabetic neuropathies provides insight on the pathophysiological mechanism and directs the clinician towards rational treatment strategies.
Höliner, Isabella; Haslinger, Vera; Lütschg, Jürg; Müller, Guido; Barbarini, Daniela Seick; Fussenegger, Jörg; Zanier, Ulrike; Saely, Christoph H; Drexel, Heinz; Simma, Burkhard
The aim of this study was to evaluate the prevalence of diabetic peripheral neuropathy in children and adolescents with type 1 diabetes mellitus and examine whether the neurological examination validly diagnoses diabetic peripheral neuropathy as compared with the gold standard of nerve conduction velocity in these patients. Nerve conduction velocity was measured in an unselected consecutive series of patients aged 8-18 years who had been suffering from type 1 diabetes mellitus for at least 1 year. For the neurological examination, neuropathy disability scores and neuropathy sign scores were used. Of the 39 patients, six (15%) had clinically evident diabetic peripheral neuropathy, whereas nerve conduction velocity testing revealed diabetic peripheral neuropathy in 15 (38%) patients. Sensitivity and specificity of the neurological examination for the diagnosis of diabetic peripheral neuropathy were 40% and 100%, respectively. The corresponding positive and negative predictive values were 100% and 72.7%, respectively. This conclusions from this study are that in children and adolescents with type 1 diabetes mellitus, diabetic peripheral neuropathy is highly prevalent, but in the majority of patients it is subclinical. Sensitivity and negative predictive values of the neurological examination are low. Therefore, routine nerve conduction velocity measurement for the assessment of diabetic peripheral neuropathy appears to be warranted in these patients.
Bordini, Brett J; Monrad, Priya
Differentiating Guillain-Barré syndrome (GBS) from inherited neuropathies and other acquired peripheral neuropathies requires understanding the atypical presentations of GBS and its variant forms, as well as historical and physical features suggestive of inherited neuropathies. GBS is typically characterized by the acute onset of ascending flaccid paralysis, areflexia, and dysesthesia secondary to peripheral nerve fiber demyelination. The disorder usually arises following a benign gastrointestinal or respiratory illness, is monophasic, reaches a nadir with several weeks, and responds to immunomodulatory therapy. Inherited neuropathies with onset before adulthood, whose presentation may mimic Guillain-Barré syndrome, are reviewed. Copyright Â© 2016 Elsevier Inc. All rights reserved.
Pratibha D Nadig
Conclusions: Tinospora cordifolia prevents the hyperalgesia in experimental diabetic neuropathy. It has an aldose reductase inhibitory activity in-vitro which may contribute to the beneficial effects.
Li, John-Michael; Rucker, Janet C
A 52-year-old woman with alcohol abuse presented with recent worsening of vision, imbalance, and confusion. Examination revealed counting fingers acuity in both eyes with central scotomas, color vision loss, horizontal nystagmus, and gait ataxia. Thiamine was initiated as treatment for a presumptive diagnosis of Wernicke encephalopathy (WE). Brain MRI revealed high T2 signal in the dorsal midbrain and thalami characteristic of WE. The lack of optic disc edema, usually present in patients with WE who have severe optic neuropathy, and lack of visual loss reversibility with thiamine treatment, led to the suspicion of coexisting Leber hereditary optic neuropathy (LHON), which was later confirmed when testing revealed the 14484 mitochondrial DNA mutation. Over the ensuing months, vision did not recover despite improvement of other neurologic findings. Irreversible optic neuropathy in WE should prompt consideration of a coexisting mitochondrial disorder such as LHON.
Full Text Available Purpose: To investigate the effect of optic neuritis (ON, ischemic optic neuropathy (ION and compressive optic neuropathy (CON on multifocal visual evoked potential (mfVEP amplitudes and latencies, and to compare the parameters among three optic nerve disorders. Materials and Methods: mfVEP was recorded for 71 eyes of controls and 48 eyes of optic nerve disorders with subgroups of optic neuritis (ON, n = 21 eyes, ischemic optic neuropathy (ION, n = 14 eyes, and compressive optic neuropathy (CON, n = 13 eyes. The size of defect in mfVEP amplitude probability plots and relative latency plots were analyzed. The pattern of the defect in amplitude probability plot was classified according to the visual field profile of optic neuritis treatment trail (ONTT. Results: Median of mfVEP amplitude (log SNR averaged across 60 sectors were reduced in ON (0.17 (0.13-0.33, ION (0.14 (0.12-0.21 and CON (0.21 (0.14-0.30 when compared to controls. The median mfVEP relative latencies compared to controls were significantly prolonged in ON and CON group of 10.53 (2.62-15.50 ms and 5.73 (2.67-14.14 ms respectively compared to ION group (2.06 (-4.09-13.02. The common mfVEP amplitude defects observed in probability plots were diffuse pattern in ON, inferior altitudinal defect in ION and temporal hemianopia in CON eyes. Conclusions: Optic nerve disorders cause reduction in mfVEP amplitudes. The extent of delayed latency noted in ischemic optic neuropathy was significantly lesser compared to subjects with optic neuritis and compressive optic neuropathy. mfVEP amplitudes can be used to objectively assess the topography of the visual field defect.
Lantos, Paul M; Tsao, Jean; Nigrovic, Lise E; Auwaerter, Paul G; Fowler, Vance G; Ruffin, Felicia; Foster, Erik; Hickling, Graham
Most Lyme disease cases in the Midwestern United States are reported in Minnesota and Wisconsin. In recent years, however, a widening geographic extent of Lyme disease has been noted with evidence of expansion eastwards into Michigan and neighboring states with historically low incidence rates. We collected confirmed and probable cases of Lyme disease from 2000 through 2014 from the Michigan Department of Health and Human Services, entering them in a geographic information system. We performed spatial focal cluster analyses to characterize Lyme disease expansion. We compared the distribution of human cases with recent Ixodes scapularis tick distribution studies. Lyme disease cases in both the Upper and Lower Peninsulas of Michigan expanded more than 5-fold over the study period. Although increases were seen throughout the Upper Peninsula, the Lower Peninsula particularly expanded along the Indiana border north along the eastern shore of Lake Michigan. Human cases corresponded to a simultaneous expansion in established I scapularis tick populations. The geographic distribution of Lyme disease cases significantly expanded in Michigan between 2000 and 2014, particularly northward along the Lake Michigan shore. If such dynamic trends continue, Michigan-and possibly neighboring areas of Indiana, Ohio, and Ontario, Canada-can expect a continued increase in Lyme disease cases.
Mozley, S.C.; Howmiller, R.P.
This report summarizes Lake Michigan zoobenthic studies up to 1974, including reports of power-plant surveys. It describes ecologies of macroinvertebrate species and some microfauna, partly through use of data from other Great Lakes. The following are discussed: methodology of field surveys; zoobenthic indicators of pollution; zoobenthic effects on sediment-water exchanges; and numbers, biomass, and production of total macroinvertebrates. Prominent features of Lake Michigan zoobenthos include predominance of the amphipod Pontoporeia affinis, usefulness of tubificid oligochaetes in mapping environmental quality, and pronounced qualitative gradients in zoobenthos in relation to depth. Further research is needed on sampling methods, energy flow rates and pathways through benthic communities, factors limiting distribution of species near shore, and effects of macroinvertebrates on sediment chemistry and structure.
Datta, Sandipan; Tomilov, Alexey; Cortopassi, Gino
Inherited mitochondrial complex I mutations cause blinding Leber's hereditary optic neuropathy (LHON), for which no curative therapy exists. A specific biochemical consequence of LHON mutations in the presence of trace rotenone was observed: deficient complex I-dependent ATP synthesis (CIDAS) and mitochondrial O2 consumption, proportional to the clinical severity of the three primary LHON mutations. We optimized a high-throughput assay of CIDAS to screen 1600 drugs to 2, papaverine and zolpidem, which protected CIDAS in LHON cells concentration-dependently. TSPO and cAMP were investigated as protective mechanisms, but a conclusive mechanism remains to be elucidated; next steps include testing in animal models.
Full Text Available Objective To summarize the clinical features and neuropathological characteristics in patients with vasculitic peripheral neuropathy (VPN. Methods Clinical manifestations, laboratory examination and neuromuscular biopsy characteristics of 11 patients with VPN were retrospectively analyzed. The lesion of nerve, muscle and skin was observed under optical and electron microscope. Immunohistochemical analyses were carried out to detect neurofilament (NF, myelin basic protein (MBP, peripheral myelin protein 22 (PMP22 and S-100 protein (S-100 and further observing the neuropathy of neuraxon, myelin sheath and Schwann cells, and to detect human leukocyte antigen DR (HLA-DR, CD68, CD3 and CD20 to observe inflammatory cell infiltration. Immunofluorescent staining was used to detect the deposition of IgA, IgM, IgG and addiment C3 on vascular wall. The staining of periodic acid-Schiff (PAS, NADH-tetrazolium reductase (NADH-TR and modified Gomori trichrome (MGT were used to judge the myopathy. Results 1 Angiopathies were mainly manifested by small vessels of epineurium and perineurium, and infiltrated inflammatory cells were mainly CD3 + T cells. Three patients had active vasculitis, and 8 patients had non-active vasculitis. Among these 8 patients, 4 patients mainly presented fibrous obliteration of blood vessel, with slight inflammatroy cell infiltration, and the other 4 patients mainly showed perivascular inflammation. 2 Neuropathy: 6 patients had axon degeneration, and 5 patients had axon degeneration associated with demyelination. All of them demonstrated a reduction in myelinated fibers, mainly large diameter myelinated fibers, even on end-stage. 3 Muscle biopsy showed neurogenic atrophy. 4 Clinicopathologic diagnosis: among these 11 patients, 8 patients were diagnosed as systemic vasculitic peripheral neuropathy (SVPN, among whom 5 patients were diagnosed as primary systemic vasculitis [including 1 patient as Churg-Strauss syndrome (CSS, 2 patients as
Banach, Marta; Antczak, Jakub; Rola, Rafał
Background Myotonic dystrophy (DM) type 1 and type 2 are inherited diseases characterized by myotonia and myopathy. Additional symptoms include, among others, peripheral neuropathy and sleep-related breathing disorders (SRBDs). There is growing evidence for a complex association between DM1 and DM2, which was described in patients with diabetes mellitus and in the general population. In this study, we investigated whether there is an association between peripheral neuropathy and SRBDs also in the population of patients with DM. Methods The study included 16 patients with DM1 (mean age, 37.9±14.1 years; 20–69 years) and eight patients with DM2 (mean age, 47.6±14.1 years; 20–65 years), who underwent a sensory and motor nerve conduction study (NCS) and diagnostic screening for SRBDs. In both groups, the NCS parameters were correlated with respiratory parameters. Results In both groups, the amplitude of the ulnar sensory nerve action potential (SNAP) correlated with the mean arterial oxygen saturation (SaO2). In addition, in the DM2 group, the median SNAP correlated with the mean SaO2. In the DM1 group, the median SNAP and the distal motor latency (DML) of the ulnar nerve correlated with the apnea–hypopnea index, while the oxygen desaturation index correlated with the DML of the tibial nerve and with conduction velocity in the sural nerve. Conclusion Our results indicate a complex association between neuropathy and SRBDs in DM1 and DM2. Axonal degeneration may contribute to nocturnal hypoxemia and vice versa. Neuropathy may contribute to muscle weakness, which in turn may cause respiratory events. PMID:28138246
Finsterer, J; Mamoli, B
Multifocal motor neuropathy, which mimics lower motor neuron disease, is a rare and curious demyelinating neuropathy characterised by slowly progressive, asymmetric limb weakness within the distribution of individual peripheral nerves, wasting, cramps, fasciculations and rare sensory involvement, but without upper motor neuron signs. The cardinal feature and primary pathophysiological basis for the weakness is the multifocal motor conduction block which remains stable for years at the same site and is confined to motor axons. It is defined as > 50% reduction in both the CMAP and the negative peak area on proximal stimulation, as compared with the distal stimulus response without any change in the negative peak duration. Nerves at the site of the conduction block show demyelination, endoneural edema, rudimentary onion bulbs and lymphocytic inflammation. Sensory nerves may show mild demyelination, axon loss and lymphocytic inflammation. The majority of patients shows elevated titers of anti-glycolipid antibodies, which may block the Na+ channels, produce demyelination or interfere with remyelination. However, their role in the pathogenesis of multifocal motor neuropathy remains uncertain. Multifocal motor neuropathy is regarded as the predominantly motor variant of chronic inflammatory demyelinating polyneuropathy and can be treated best with immunoglobulins and cyclophosphamide.
Thiel, Daniel B; Platt, Tevah; Platt, Jodyn; King, Susan B; Kardia, Sharon L R
Biobanks raise challenges for developing ethically sound and practicable consent policies. Biobanks comprised of dried bloodspots (DBS) left over from newborn screening, maintained for long-term storage, and potential secondary research applications are no exception. Michigan has been a leader in transforming its DBS collection, marketing its biobank of de-identified samples for health research use. The Michigan BioTrust for Health includes approximately 4 million unconsented retrospective samples collected as early as 1984 and prospective samples added since the fall of 2010 with blanket parental consent. We engaged Michigan citizens to ascertain public attitudes, knowledge, and beliefs about the BioTrust and informed consent. A convenience sampling of 393 participants from communities around the state of Michigan (oversampling for minority populations) participated in meetings addressing newborn screening, the BioTrust and informed consent, yielding quantitative and qualitative survey and discussion data. Participants affirmed the principle of voluntary informed participation in research and advocated for greater public awareness of the existence of the BioTrust. Most expressed support for the use of DBS for research and a desire for greater involvement in granting permission for research use. Opinions varied as to which specific research uses were acceptable. Participants indicated a desire for greater engagement, public awareness, and more active decision making on the part of biobank participants and parents. Diversity of opinion over which research areas were deemed acceptable problematizes the blanket consent model that currently applies to the BioTrust's prospective DBS collection and that could become the new norm for research using de-identified data under proposed changes to the Common Rule.
Pott, Jan Willem R.; Wong, Kwok H.
Background: Leber's hereditary optic neuropathy (LHON) is a maternally inherited optic neuropathy caused by mutations in mitochondrial DNA (mtDNA). It is also believed that several epigenetic factors have an influence on the development of LHON. Methods: A case series was observed. Results: Three pa
Shabo, G.; Scheffer, H.; Cruysberg, J.R.M.; Lammens, M.M.Y.; Pasman, J.W.; Spruit, M.; Willemsen, M.A.A.P.
Congenital cataracts facial dysmorphism neuropathy syndrome is a recently delineated autosomal recessive condition exclusively found in the Gypsy population. Congenital cataracts facial dysmorphism neuropathy syndrome is caused by a homozygous mutation in the CTDP1 gene, leading to disruption of the
Helmich, Rick C G; van Laarhoven, Hanneke W M; Schoonderwaldt, Hennie C; Janssen, Mirian C H
Rhabdomyolysis and peripheral neuropathy are two distinct disease entities which are rarely encountered in combination. We present a woman with rhabdomyolysis and peripheral neuropathy 3 weeks postpartum. Her symptoms were caused by bilateral femoral artery thrombosis due to postpartum cardiomyopathy (PPCM). This demonstrates that PPCM may present with predominantly non-cardial symptoms and underscores the importance of rapidly recognizing this disorder.
Pott, Jan Willem R.; Wong, Kwok H.
Background: Leber's hereditary optic neuropathy (LHON) is a maternally inherited optic neuropathy caused by mutations in mitochondrial DNA (mtDNA). It is also believed that several epigenetic factors have an influence on the development of LHON. Methods: A case series was observed. Results: Three
Saporta, Mario A
Inherited peripheral neuropathies are among the most common genetic neuromuscular disorders worldwide. However, their diagnosis can be challenging due to genotypic and phenotypic variability. Charcot-Marie-Tooth disease (CMT), the most common form, is associated with mutations or copy-number variations in over 70 genes, representing proteins with fundamental roles in the development and function of Schwann cells and peripheral axons. Other genetic peripheral neuropathies are associated with multisystem manifestations, including familial amyloid neuropathy and neuropathies associated with metabolic or other genetic syndromes. This article reviews the most recent discoveries in the field and how they are changing the way neurologists diagnose this specific group of peripheral neuropathies. In the past few years, several large cohort studies on the molecular diagnosis of CMT have been published, providing guidelines for genetic testing in clinical practice. In the same period, next-generation sequencing technology has accelerated the discovery of new CMT genes, expanding our knowledge on genotype-phenotype correlations. Recent advances in sequencing technology and genotype-phenotype correlation studies are changing the way neurologists diagnose inherited neuropathies. New therapeutic strategies for familial amyloid neuropathy are paving the way for innovative treatments for genetic neuropathies.
S. Kambiz (Shoista); J.W. van Neck (Han); S.G. Cosgun (Saniye G.); M.H.N. van Velzen (M. H N); J.A.M.J.L. Janssen (Joseph); Avazverdi, N. (Naim); S.E.R. Hovius (Steven); E.T. Walbeehm (Erik)
textabstractThe skin's rewarming rate of diabetic patients is used as a diagnostic tool for early diagnosis of diabetic neuropathy. At present, the relationship between microvascular changes in the skin and diabetic neuropathy is unclear in streptozotocin (STZ) diabetic rats. The aim of this study w
Kambiz, S.; Neck, J.W. van; Cosgun, S.G.; Velzen, M.H. van; Janssen, J.A.M.; Avazverdi, N.; Hovius, S.E.; Walbeehm, E.T.
The skin's rewarming rate of diabetic patients is used as a diagnostic tool for early diagnosis of diabetic neuropathy. At present, the relationship between microvascular changes in the skin and diabetic neuropathy is unclear in streptozotocin (STZ) diabetic rats. The aim of this study was to invest
Ozyurek, Hamit; Turker, Hande; Akbalik, Mehtap; Bayrak, Ayse Oytun; Ince, Hulya; Duru, Feride
Vincristine is a commonly used antineoplastic drug and frequently causes neurotoxicity. Here the authors report a 4-year-old boy with acute lymphoblastic leukemia in whom vincristine-induced peripheral and cranial neuropathy developed during remission induction therapy. The patient seemed to benefit from pyridoxine and pyridostigmine therapy greatly and this therapy is recommended in patients with severe vincristine-induced neuropathy.
Meadows, G G; Huff, M R; Fredericks, S
Tricyclic antidepressants rarely cause peripheral neuropathy. In fact, this class of drugs has been used to control the symptoms of pain and paresthesia that accompany peripheral neuropathy. We report peripheral paresthesias that occurred in a 39-year-old female during five years of amitriptyline administration. The patient's symptoms were relieved by oral pyridoxine hydrochloride, associated with elevated plasma pyridoxal phosphate.
de Jager, AEJ; van der Hoeven, JH
Objective - To investigate the effect of Rhesus anti-D immunoglobulin (anti-D) in patients with an autoimmune demyelinating neuropathy. Material and methods - Three patients with an autoimmune mediated neuropathy received 1000 IU anti-D weekly for 2 months. Results - Two patients worsened gradually
Outlines the reasons for, and the problems involved in, separation of a research center from the University of Michigan in order to become an independent research organization contracting for private and military research. (AL)
Army Corps of Engineers, Department of the Army, Department of Defense — The Joint Airborne Lidar Bathymetry Technical Center of Expertise (JALBTCX) has performed a coastal survey along the MI coasts of Lake Superior, Lake Michigan and...
Guangqian Xing; Xingkuan Bu; Dengyuan Wang; Ling Lu
Objective: To analyze neurophysiological characteristics in infants and young children with auditory neuropathy (AN) and explore their clinical significance. Methods: Audiological measurements(acoustic immittance, EOAEs, ABR, CM, MLR and ERPs) and peripheral neurological tests were conducted and evaluated in 13 infants and young children with AN. Six of them received highresolution temporal bone CT scans and/or cerebral MRI examinations. Results: All of the children showed type "A" tympanograms with abseatation of stapedial reflexes. EOAEs were normal in 12 of 13 subjects. In one child who had a history of anoxia during the birth, the EOAEs were not elicited. Click-evoked ABRs were absent in 12 of 13 subjects when maximum output of the instrument was reached. The CM potentials were presented bilaterally in all individuals, which were independent of the EOAEs and ABR. Of eight cases tested, all had clear MLR and six showed normal ERPs(P300 and MMN). Peripheral neurological tests and radiological findings were within the normal ranges. Conclusion: The diagnosis of AN in infants and young children should focus on analyzing their neurophysiological characteristics,especially on CM,MLR and ERPs. Combined use of EOAEs, ABR and CM was recommended for hearing screening on newborns with high risk factors.
Mamou, Fatema*; Henderson, Tiffany
Objective The purpose of this work was to conduct an enhanced analysis of heat illness during a heat wave using Michigan?s Emergency Department Syndromic Surveillance System (MSSS) that could be provided to Public Health and Preparedness Stakeholders for situational awareness. Introduction The MSSS, described elsewhere (1), has been in use since 2003 and records Emergency Department (ED) chief complaint data along with the patient?s age, gender and zip code in real time. There were 85/139 hos...
Madenjian, Charles P.; Breidert, Brian; Boyarski, David; Bronte, Charles R.; Dickinson, Ben; Donner, Kevin; Ebener, Mark P.; Gordon, Roger; Hanson, Dale; Holey, Mark; Janssen, John; Jonas, Jory; Kornis, Matthew; Olsen, Erik; Robillard, Steve; Treska, Ted; Weldon, Barry; Wright, Greg D.
This report provides a review on the progression of lake trout rehabilitation towards meeting the Salmonine Fish Community Objectives (FCOs) for Lake Michigan (Eshenroder et. al. 1995) and the interim goal and evaluation objectives articulated in A Fisheries Management Implementation Strategy for the Rehabilitation of Lake Trout in Lake Michigan (Dexter et al. 2011); we also include data describing lake trout stocking and mortality to portray the present state of progress towards lake trout rehabilitation.
Hirunwiwatkul, Parima; Trobe, Jonathan D
Optic neuropathy is an uncommon manifestation of relapsing polychondritis (RPC), a rare systemic disease affecting cartilaginous and proteoglycan-rich structures. The optic neuropathy has been attributed to ischemia, intrinsic inflammation of the optic nerve, or spread of inflammation to the nerve from adjacent intraconal orbital tissues. We report a case of recurrent corticosteroid-responsive optic neuropathy in which MRI did not show ocular, optic nerve, or intraconal orbital abnormalities but did show periosteal thickening and enhancement in the apical orbit and adjacent intracranial space consistent with periostitis. The periostitis, which is a manifestation of a systemic vasculitis or an autoimmune reaction to progenitors of cartilage, probably caused the optic neuropathy by compression or inflammation. It is important to recognize this mechanism of optic neuropathy as its imaging features may be a subtle yet critical clue to an underlying systemic condition that can be life-threatening if not properly managed.
Taskiran, Mustafa; Fritz-Hansen, Thomas; Rasmussen, Verner
The pathophysiological mechanisms responsible for increased cardiovascular mortality in diabetic autonomic neuropathy are unknown. To investigate the effect of autonomic neuropathy on myocardial function, we performed dynamic contrast-enhanced magnetic resonance perfusion imaging during baseline...... conditions and after Dipyridamole-induced vasodilatation in nine type 1 diabetic patients with autonomic neuropathy (AN+), defined by cardiovascular tests, as well as in 10 type 1 diabetic patients without autonomic neuropathy (AN-) and 10 healthy control subjects. Baseline myocardial perfusion index (K...... blood pressure response to Dipyridamole and myocardial perfusion reserve index. We conclude that type 1 diabetic patients with autonomic neuropathy have a decreased myocardial perfusion reserve capacity when challenged with a vasodilatator, a finding that may in part be the pathophysiological substrate...
Lin, Cindy S-Y; Lee, Ming-Jen; Park, Susanna B; Kiernan, Matthew C
The porphyrias are inherited metabolic disorders arising from disturbance in the haem biosynthesis pathway. The neuropathy associated with acute intermittent porphyria (AIP) occurs due to mutation involving the enzyme porphobilinogen deaminase (PBGD) and is characterised by motor-predominant features. Definitive diagnosis often encompasses a combination of biochemical, enzyme analysis and genetic testing, with clinical neurophysiological findings of a predominantly motor axonal neuropathy. Symptomatic and supportive treatment are the mainstays during an acute attack. If administered early, intravenous haemin may prevent progression of neuropathy. While the pathophysiology of AIP neuropathy remains unclear, axonal dysfunction appears intrinsically linked to the effects of neural energy deficits acquired through haem deficiency coupled to the neurotoxic effects of porphyrin precursors. The present review will provide an overview of AIP neuropathy, including discussion of recent advances in understanding developed through neurophysiological approaches that have further delineated the pathophysiology of axonal degeneration.
Grimm, Alexander; Décard, Bernhard F; Bischof, Antje; Axer, Hubertus
Ultrasound of the peripheral nerves (PNUS) can be used to visualize nerve pathologies in polyneuropathies (PNP). The aim of this study was to investigate, whether PNUS provides additional information in patients with proven systemic vasculitic neuropathies (VN). Systematic ultrasound measurements of several peripheral nerves, the vagal nerve and the 6th cervical nerve root were performed in 14 patients and 22 healthy controls. Nerve conduction studies of the corresponding nerves were undertaken. Finally, the measured results were compared to a study population of demyelinating immune-mediated and axonal neuropathies. Patients with VN displayed significant smaller amplitudes of compound muscle action potentials (CMAP) (pneuropathies than in other axonal neuropathies, but significantly rarer than in demyelinating neuropathies. Focal CSA enlargement in one or more nerves in electrophysiologically axonal neuropathies can be a hint for VN and thus facilitate diagnostic and therapeutic procedures. Copyright © 2014 Elsevier B.V. All rights reserved.
Hilsted, J; Richter, E; Madsbad, S
. To study these responses, we administered epinephrine in a graded intravenous infusion (0.5 to 5 micrograms per minute) to seven diabetic patients without neuropathy, seven diabetic patients with autonomic neuropathy, and seven normal subjects. Mean arterial pressure decreased significantly in the patients...... with autonomic neuropathy than in the other groups (P less than 0.05). These findings indicate that several beta-receptor-mediated responses to epinephrine are enhanced in patients with diabetic autonomic neuropathy. The underlying mechanism remains to be elucidated.......Norepinephrine-induced vasoconstriction, which is mediated by alpha-adrenergic receptors, is accentuated in patients with autonomic neuropathy. In contrast, responses mediated by beta-adrenergic receptors, including vasodilatation and metabolic changes, have not been evaluated in these patients...
Caporali, Leonardo; Maresca, Alessandra; Capristo, Mariantonietta; Del Dotto, Valentina; Tagliavini, Francesca; Valentino, Maria Lucia; La Morgia, Chiara; Carelli, Valerio
Incomplete penetrance characterizes the two most frequent inherited optic neuropathies, Leber's Hereditary Optic Neuropathy (LHON) and dominant optic atrophy (DOA), due to genetic errors in the mitochondrial DNA (mtDNA) and the nuclear DNA (nDNA), respectively. For LHON, compelling evidence has accumulated on the complex interplay of mtDNA haplogroups and environmental interacting factors, whereas the nDNA remains essentially non informative. However, a compensatory mechanism of activated mitochondrial biogenesis and increased mtDNA copy number, possibly driven by a permissive nDNA background, is documented in LHON; when successful it maintains unaffected the mutation carriers, but in some individuals it might be hampered by tobacco smoking or other environmental factors, resulting in disease onset. In females, mitochondrial biogenesis is promoted and maintained within the compensatory range by estrogens, partially explaining the gender bias in LHON. Concerning DOA, none of the above mechanisms has been fully explored, thus mtDNA haplogroups, environmental factors such as tobacco and alcohol, and further nDNA variants may all participate as protective factors or, on the contrary, favor disease expression and severity. Next generation sequencing, complemented by transcriptomics and proteomics, may provide some answers in the next future, even if the multifactorial model that seems to apply to incomplete penetrance in mitochondrial optic neuropathies remains problematic, and careful stratification of patients will play a key role for data interpretation. The deep understanding of which factors impinge on incomplete penetrance may shed light on the pathogenic mechanisms leading to optic nerve atrophy, on their possible compensation and, thus, on development of therapeutic strategies. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.
Ramakrishnan, Reshma; Shrivastava, Saurabh; Deshpande, Shrikant; Patkar, Priyanka
Dengue fever is caused by a flavivirus. This infection is endemic in the tropics and warm temperate regions of the world. Ocular manifestations of dengue fever include subconjunctival, vitreous, and retinal haemorrhages; posterior uveitis; optic neuritis; and maculopathies, haemorrhage, and oedema. However anterior ischemic optic neuropathy is a rare presentation. Optic nerve ischemia most frequently occurs at the optic nerve head, where structural crowding of nerve fibers and reduction of the vascular supply may combine to impair perfusion to a critical degree and produce optic disc oedema. Here we present a case of anterior ischemic optic neurapathy associated with dengue fever.
Muhammed Jasim Abdul Jalal
Full Text Available Case: A 30 year old male presented with numbness of palms and soles followed by weakness of upper limbs and lower limbs of 5 days duration, which was ascending and progressive. Three months back he was treated for oral and genital ulcers with oral steroids. His ulcers improved and shifted to indigenous medication. His clinical examination showed polyneuropathy. CSF study did not show albuminocytological dissociation. Nerve conduction study showed demyelinating polyneuropathy. His blood samples and the ayurvedic drug samples were sent for toxicological analysis. Inference: Acute toxic neuropathy - Arsenic
Full Text Available Recurrent painful ophthalmoplegic neuropathy, typically seen as a serious childhood migraine attack which is followed by ptosis and diplopia due to oculomotor nerve palsy. This is regarded as a form of migraine in the previous classifications but according to the latest classification of the International Headache Society has been recognized as cranial neuralgia. Due to the poor pathological and radiological findings of oculomotor nerve during attack, it is difficult to make differential diagnosis. In this manuscript we report 11-year-old female patient with ophtalmoplegic migraine. [Cukurova Med J 2014; 39(4.000: 938-941
Svendsen, Susanne Wulff; Juhl, Anne Haase
Three months after he was employed as a poultry worker, a 48-year-old man developed involuntary jerks of his right first, fourth, and fifth fingers, paraesthesiae, weakness, and eventually wasting of the first dorsal interosseous muscle. His job entailed repetitive lifting of boxes weighing 10-25 kg with flexion of the elbow, pronation of the forearm, and ulnar deviation of the wrist. A nerve conduction study indicated ulnar neuropathy just distal to the elbow. Surgery at this level alleviated the symptoms, but shortly after his return to work, he changed jobs because of aggravation.
Deltombe, T; Hanson, P; Boutsen, Y; Laloux, P; Clerin, M
Lyme borreliosis is responsible for a large variety of peripheral neurologic manifestations including axonal polyneuropathy, radiculopathy, and facial nerve palsy. The prevalence of the disease must draw our attention on the possible responsibility of Borrelia burgdorferi in the pathogenesis of such symptomatology. Electrophysiologic studies demonstrate a proximal and distal axonal involvement, whereas neuropathologic studies suggest that vasculitis might be one of the primary pathophysiologic mechanisms. Electromyography provides a useful diagnostic tool and an important measure of response to treatment. Although peripheral neuropathy usually improves, our case report confirms the fact that chronic neurologic manifestations may not consistently resolve with appropriate treatment.
SCHERER, STEVEN S.; WRABETZ, LAWRENCE
The past 15 years have witnessed the identification of more than 25 genes responsible for inherited neuropathies in humans, many associated with primary alterations of the myelin sheath. A remarkable body of work in patients, as well as animal and cellular models, has defined the clinical and molecular genetics of these illnesses and shed light on how mutations in associated genes produce the heterogeneity of dysmyelinating and demyelinating phenotypes. Here, we review selected recent developments from work on the molecular mechanisms of these disorders and their implications for treatment strategies. PMID:18803325
Landau, Mark E; Campbell, William W
In this review, we delineate clinical, electrodiagnostic, and radiographic features of ulnar mononeuropathies. Ulnar neuropathy at the elbow (UNE) is most commonly due to lesions at the level of the retroepicondylar groove (RTC), with approximately 25% at the humeroulnar arcade (HUA). The term 'cubital tunnel syndrome' should be reserved for the latter. The diagnostic accuracy of nerve conduction studies is limited by biological (e.g. low elbow temperature) and technical factors. Across-elbow distance measurements greater than 10 cm improve diagnostic specificity at the expense of decreased sensitivity. Short-segment incremental studies can differentiate lesions at the HUA from those at the RTC.
Wim H van Brakel
Full Text Available BACKGROUND: Leprosy is the most frequent treatable neuromuscular disease. Yet, every year, thousands of patients develop permanent peripheral nerve damage as a result of leprosy. Since early detection and treatment of neuropathy in leprosy has strong preventive potential, we conducted a cohort study to determine which test detects this neuropathy earliest. METHODS AND FINDINGS: One hundred and eighty-eight multibacillary (MB leprosy patients were selected from a cohort of 303 and followed for 2 years after diagnosis. Nerve function was evaluated at each visit using nerve conduction (NC, quantitative thermal sensory testing and vibrometry, dynamometry, monofilament testing (MFT, and voluntary muscle testing (VMT. Study outcomes were sensory and motor impairment detected by MFT or VMT. Seventy-four of 188 patients (39% had a reaction, neuritis, or new nerve function impairment (NFI event during a 2-year follow-up. Sub-clinical neuropathy was extensive (20%-50%, even in patients who did not develop an outcome event. Sensory nerve action potential (SNAP amplitudes, compound motor action potential (CMAP velocities, and warm detection thresholds (WDT were most frequently affected, with SNAP impairment frequencies ranging from 30% (median to 69% (sural. Velocity was impaired in up to 43% of motor nerves. WDTs were more frequently affected than cold detection thresholds (29% versus 13%, ulnar nerve. Impairment of SNC and warm perception often preceded deterioration in MF or VMT scores by 12 weeks or more. CONCLUSIONS: A large proportion of leprosy patients have subclinical neuropathy that was not evident when only MFT and VMT were used. SNC was the most frequently and earliest affected test, closely followed by WDT. They are promising tests for improving early detection of neuropathy, as they often became abnormal 12 weeks or more before an abnormal monofilament test. Changes in MFT and VMT score mirrored changes in neurophysiology, confirming their
Mustapa, Amirah; Justine, Maria; Mohd Mustafah, Nadia; Jamil, Nursuriati; Manaf, Haidzir
Purpose. The aim of this paper is to review the published studies on the characteristics of impairments in the postural control and gait performance in diabetic peripheral neuropathy (DPN). Methods. A review was performed by obtaining publication of all papers reporting on the postural control and gait performance in DPN from Google Scholar, Ovid, SAGE, Springerlink, Science Direct (SD), EBSCO Discovery Service, and Web of Science databases. The keywords used for searching were "postural control," "balance," "gait performance," "diabetes mellitus," and "diabetic peripheral neuropathy." Results. Total of 4,337 studies were hit in the search. 1,524 studies were screened on their titles and citations. Then, 79 studies were screened on their abstract. Only 38 studies were eligible to be selected: 17 studies on postural control and 21 studies on the gait performance. Most previous researches were found to have strong evidence of postural control impairments and noticeable gait deficits in DPN. Deterioration of somatosensory, visual, and vestibular systems with the pathologic condition of diabetes on cognitive impairment causes further instability of postural and gait performance in DPN. Conclusions. Postural instability and gait imbalance in DPN may contribute to high risk of fall incidence, especially in the geriatric population. Thus, further works are crucial to highlight this fact in the hospital based and community adults.
Mustapa, Amirah; Mohd Mustafah, Nadia; Jamil, Nursuriati
Purpose. The aim of this paper is to review the published studies on the characteristics of impairments in the postural control and gait performance in diabetic peripheral neuropathy (DPN). Methods. A review was performed by obtaining publication of all papers reporting on the postural control and gait performance in DPN from Google Scholar, Ovid, SAGE, Springerlink, Science Direct (SD), EBSCO Discovery Service, and Web of Science databases. The keywords used for searching were “postural control,” “balance,” “gait performance,” “diabetes mellitus,” and “diabetic peripheral neuropathy.” Results. Total of 4,337 studies were hit in the search. 1,524 studies were screened on their titles and citations. Then, 79 studies were screened on their abstract. Only 38 studies were eligible to be selected: 17 studies on postural control and 21 studies on the gait performance. Most previous researches were found to have strong evidence of postural control impairments and noticeable gait deficits in DPN. Deterioration of somatosensory, visual, and vestibular systems with the pathologic condition of diabetes on cognitive impairment causes further instability of postural and gait performance in DPN. Conclusions. Postural instability and gait imbalance in DPN may contribute to high risk of fall incidence, especially in the geriatric population. Thus, further works are crucial to highlight this fact in the hospital based and community adults. PMID:27525281
Julio C Rojas
Full Text Available Julio C Rojas, Francisco Gonzalez-LimaDepartments of Psychology, Pharmacology and Toxicology, University of Texas at Austin, Austin, TX, USAAbstract: This review summarizes the characteristics of a rodent toxicologic model of optic neuropathy induced by the mitochondrial complex I inhibitor rotenone. This model has been developed to fulfill the demand for a drug-screening tool providing a sound mechanistic context to address the role of mitochondrial dysfunction in the pathogenesis of neurodegenerative disorders. It features biochemical, structural, and functional retinal deficits that resemble those of patients with Leber’s hereditary optic neuropathy, a mitochondrial disease characterized by selective degeneration of retinal ganglion cells, and for which an environmental component is believed to play a major triggering role. The available data support the efficiency, sensitivity, and versatility of the model for providing insights into the mechanisms of neurodegeneration, including mitochondrial dysfunction, oxidative stress and excitotoxicity. Screening work with this model has provided proof-of-principle that interventions targeting the electron transport chain, such as USP methylene blue and near-infrared light therapy, are effective at preventing neurodegeneration induced by mitochondrial dysfunction in vivo. Prospective developments of this model include the use of neuronal reporter genes for in vivo non-invasive assessment of retinal degeneration at different time points, and its combination with genetic approaches to elucidate the synergism of environmental and genetic factors in neurodegeneration.Keywords: animal model, neuroprotection, mitochondrial dysfunction, visual function, oxidative stress, cytochrome oxidase
Full Text Available Purpose. The aim of this paper is to review the published studies on the characteristics of impairments in the postural control and gait performance in diabetic peripheral neuropathy (DPN. Methods. A review was performed by obtaining publication of all papers reporting on the postural control and gait performance in DPN from Google Scholar, Ovid, SAGE, Springerlink, Science Direct (SD, EBSCO Discovery Service, and Web of Science databases. The keywords used for searching were “postural control,” “balance,” “gait performance,” “diabetes mellitus,” and “diabetic peripheral neuropathy.” Results. Total of 4,337 studies were hit in the search. 1,524 studies were screened on their titles and citations. Then, 79 studies were screened on their abstract. Only 38 studies were eligible to be selected: 17 studies on postural control and 21 studies on the gait performance. Most previous researches were found to have strong evidence of postural control impairments and noticeable gait deficits in DPN. Deterioration of somatosensory, visual, and vestibular systems with the pathologic condition of diabetes on cognitive impairment causes further instability of postural and gait performance in DPN. Conclusions. Postural instability and gait imbalance in DPN may contribute to high risk of fall incidence, especially in the geriatric population. Thus, further works are crucial to highlight this fact in the hospital based and community adults.
Petzold, Axel; Plant, Gordon T
The spectrum of autoimmune optic neuropathies (ON) is extending. The phenotypic spectrum includes single isolated optic neuritis (SION), relapsing isolated optic neuritis (RION), chronic relapsing inflammatory optic neuropathy (CRION), the neuromyelitis optica (NMO) spectrum disorder, multiple sclerosis associated optic neuritis (MSON) and unclassified optic neuritis (UCON) forms. Epidemiological data suggests a slight female predominance. The ethnic heritage is relevant as Caucasian patients are more likely to suffer from MSON, whilst SION, RION, CRION and NMO are more frequent in non-Caucasian patients. Importantly, prognosis for recovery of visual function is good in MSON, but poorer in NMO and CRION which also have a high chance for recurrent episodes. Testing for serum anti-AQP4 autoantibodies is advised in all patients with severe, atypical or recurrent ON because of the high diagnostic specificity. The diagnostic specificity may be aided by testing for glial biomarkers in the CSF and prognostic accuracy by testing for biomarkers for neuroaxonal degeneration. Optical coherence tomography is a highly accurate tool to document the final outcome. The current clinical classification criteria rely on the phenotype, response to treatment and presence of anti-AQP4 autoantibodies.
Girish Baburao Kulkarni
Full Text Available Episodic transient neurological symptoms are an important set of problems presenting to a neurologist in his routine practice. Occasionally, detailed clinical history including past and family history supplemented with focused examination can bring out a rare cause for such symptoms. We describe in this report in a young male presenting with episodic focal neurological dysfunction, with family history of similar episodes in mother and brother. Examination showed features of pes cavus and peripheral neuropathy for which patient was asymptomatic. Mother and brother were established cases of hereditary neuropathy. Imaging on multiple occasions showed reversible white matter abnormalities. Clinical suspicion of X-linked Charcot-Marie-Tooth disease type 1 (CMT1X was confirmed with detection of mutation in Gap Junction B1 (GJB1 gene, which codes for connexin 32 protein (c.425G>A; p.R142Q hemizygous mutation. Though this mutation has been already reported in CMTX patients, it has not been associated with transient neurological dysfunctions. This is probably the first reported case of CMTX patient with transient neurological dysfunction from India, whose family members had similar episodes.
Mizisin, Andrew P
As ensheathing and secretory cells, Schwann cells are a ubiquitous and vital component of the endoneurial microenvironment of peripheral nerves. The interdependence of axons and their ensheathing Schwann cells predisposes each to the impact of injury in the other. Further, the dependence of the blood-nerve interface on trophic support from Schwann cells during development, adulthood, and after injury suggests these glial cells promote the structural and functional integrity of nerve trunks. Here, the developmental origin, injury-induced changes, and mature myelinating and nonmyelinating phenotypes of Schwann cells are reviewed prior to a description of nerve fiber pathology and consideration of pathogenic mechanisms in human and experimental diabetic neuropathy. A fundamental role for aldose-reductase-containing Schwann cells in the pathogenesis of diabetic neuropathy, as well as the interrelationship of pathogenic mechanisms, is indicated by the sensitivity of hyperglycemia-induced biochemical alterations, such as polyol pathway flux, formation of reactive oxygen species, generation of advanced glycosylation end products (AGEs) and deficient neurotrophic support, to blocking polyol pathway flux.
Meyerson, Cherise; Van Stavern, Greg; McClelland, Collin
Leber hereditary optic neuropathy (LHON) is one of the most common inherited optic neuropathies causing bilateral central vision loss. The disorder results from point mutations in mitochondrial DNA and subsequent mitochondrial dysfunction. The primary cell type that is lost in LHON is the retinal ganglion cell, which is highly susceptible to disrupted ATP production and oxidative stress. Inheritance of LHON follows that of mitochondrial genetics, and it has a highly variable clinical phenotype, as other genetic and environmental factors also play a role. Although LHON usually presents with isolated vision loss, some patients suffer other neurological sequelae. For ill-defined reasons, male LHON mutation carriers are more affected than females. Most LHON patients remain legally blind, but a small proportion can experience spontaneous partial recovery, often within the first year of symptom onset. Unfortunately, at this time there are no established curative interventions and treatment is largely supportive. Patients should be offered low vision services and counseled on mitigating risk factors for additional vision loss, such as smoking and consuming alcohol. Encouraging treatments currently undergoing investigation includes ubiquinone analogs, such as idebenone, as well as gene therapy and stem cells to restore ATP synthesis and provide neuroprotection to surviving retinal ganglion cells.
Meyerson, Cherise; Van Stavern, Greg; McClelland, Collin
Leber hereditary optic neuropathy (LHON) is one of the most common inherited optic neuropathies causing bilateral central vision loss. The disorder results from point mutations in mitochondrial DNA and subsequent mitochondrial dysfunction. The primary cell type that is lost in LHON is the retinal ganglion cell, which is highly susceptible to disrupted ATP production and oxidative stress. Inheritance of LHON follows that of mitochondrial genetics, and it has a highly variable clinical phenotype, as other genetic and environmental factors also play a role. Although LHON usually presents with isolated vision loss, some patients suffer other neurological sequelae. For ill-defined reasons, male LHON mutation carriers are more affected than females. Most LHON patients remain legally blind, but a small proportion can experience spontaneous partial recovery, often within the first year of symptom onset. Unfortunately, at this time there are no established curative interventions and treatment is largely supportive. Patients should be offered low vision services and counseled on mitigating risk factors for additional vision loss, such as smoking and consuming alcohol. Encouraging treatments currently undergoing investigation includes ubiquinone analogs, such as idebenone, as well as gene therapy and stem cells to restore ATP synthesis and provide neuroprotection to surviving retinal ganglion cells. PMID:26170609
Maxim Dobretsov; Dmitry Romanovsky; Joseph R Stimers
Peripheral neuropathy, and specifically distal peripheral neuropathy (DPN), is one of the most frequent and troublesome complications of diabetes mellitus. It is the major reason for morbidity and mortality among diabetic patients, It is also frequently associated with debilitating pain. Unfortunately, our knowledge of the natural history and pathogenesis of this disease remains limited. For a long time hyperglycemia was viewed as a major, if not the sole factor, responsible for all symptomatic presentations of DPN. Multiple clinical observations and animal studies supported this view. The control of blood glucose as an obligatory step of therapy to delay or reverse DPN is no longer an arguable issue. However, while supporting evidence for the glycemic hypothesis has accumulated, multiple controversies accumulated as well.It is obvious now that DPN cannot be fully understood without considering factors besides hyperglycemia. Some symptoms of DPN may develop with little, if any, correlation with the glycemic status of a patient. It is also clear that identification of these putative non-glycemic mechanisms of DPN is of utmost importance for our understanding of failures with existing treatments and for the development of new approaches for diagnosis and therapy of DPN. In this work we will review the strengths and weaknesses of the glycemic hypothesis, focusing on clinical and animal data and on the pathogenesis of early stages and triggers of DPN other than hyperglycemia.
Chekh, Viktor; Soliz, Peter; McGrew, Elizabeth; Barriga, Simon; Burge, Mark; Luan, Shuang
Diabetic peripheral neuropathy (DPN) refers to the nerve damage that can occur in diabetes patients. It most often affects the extremities, such as the feet, and can lead to peripheral vascular disease, deformity, infection, ulceration, and even amputation. The key to managing diabetic foot is prevention and early detection. Unfortunately, current existing diagnostic techniques are mostly based on patient sensations and exhibit significant inter- and intra-observer differences. We have developed a computer aided diagnostic (CAD) system for diabetic peripheral neuropathy. The thermal response of the feet of diabetic patients following cold stimulus is captured using an infrared camera. The plantar foot in the images from a thermal video are segmented and registered for tracking points or specific regions. The temperature recovery of each point on the plantar foot is extracted using our bio-thermal model and analyzed. The regions that exhibit abnormal ability to recover are automatically identified to aid the physicians to recognize problematic areas. The key to our CAD system is the segmentation of infrared video. The main challenges for segmenting infrared video compared to normal digital video are (1) as the foot warms up, it also warms up the surrounding, creating an ever changing contrast; and (2) there may be significant motion during imaging. To overcome this, a hybrid segmentation algorithm was developed based on a number of techniques such as continuous max-flow, model based segmentation, shape preservation, convex hull, and temperature normalization. Verifications of the automatic segmentation and registration using manual segmentation and markers show good agreement.
Auer-Grumbach, Michaela; Mauko, Barbara; Auer-Grumbach, Piet; Pieber, Thomas R
Hereditary sensory neuropathies (HSN), also known as hereditary sensory and autonomic neuropathies (HSAN), are a clinically and genetically heterogeneous group of disorders. They are caused by neuronal atrophy and degeneration, predominantly affecting peripheral sensory and autonomic neurons. Both congenital and juvenile to adulthood onset is possible. Currently, the classification of the HSN depends on the mode of inheritance, age at onset, and clinical presentation. Hallmark features are progressive sensory loss, chronic skin ulcers, and other skin abnormalities. Spontaneous fractures and neuropathic arthropathy are frequent complications and often necessitate amputations. Autonomic features vary between different subgroups. Distal muscle weakness and wasting may be present and is sometimes so prominent that it becomes difficult to distinguish HSN from Charcot-Marie-Tooth syndrome. Recent major advances in molecular genetics have led to the identification of seven gene loci and six-disease causing genes for autosomal-dominant and autosomal-recessive HSN. These genes have been shown to play roles in lipid metabolism and the regulation of intracellular vesicular transport, but also a presumptive transcriptional regulator, a nerve growth factor receptor, and a nerve growth factor have been described among the causative genes in HSN. Nevertheless, it remains unclear how mutations in the known genes lead to the phenotype of HSN. In this review, we summarize the recent progress of the molecular genetics of the HSN and the implicated genes.
Chance, Phillip F
Hereditary neuropathy with liability to pressure palsies (HNPP; also called tomaculous neuropathy) is an autosomal-dominant disorder that produces a painless episodic, recurrent, focal demyelinating neuropathy. HNPP generally develops during adolescence, and may cause attacks of numbness, muscular weakness, and atrophy. Peroneal palsies, carpal tunnel syndrome, and other entrapment neuropathies may be frequent manifestations of HNPP. Motor and sensory nerve conduction velocities may be reduced in clinically affected patients, as well as in asymptomatic gene carriers. The histopathological changes observed in peripheral nerves of HNPP patients include segmental demyelination and tomaculous or "sausage-like" formations. Mild overlap of clinical features with Charcot-Marie-Tooth (CMT) disease type 1 (CMT1) may lead patients with HNPP to be misdiagnosed as having CMT1. HNPP and CMT1 are both demyelinating neuropathies, however, their clinical, pathological, and electrophysiological features are quite distinct. HNPP is most frequently associated with a 1.4-Mb pair deletion on chromosome 17p12. A duplication of the identical region leads to CMT1A. Both HNPP and CMT1A result from a dosage effect of the PMP22 gene, which is contained within the deleted/duplicated region. This is reflected in reduced mRNA and protein levels in sural nerve biopsy samples from HNPP patients. Treatment for HNPP consists of preventative and symptom-easing measures. Hereditary neuralgic amyotrophy (HNA; also called familial brachial plexus neuropathy) is an autosomal-dominant disorder causing episodes of paralysis and muscle weakness initiated by severe pain. Individuals with HNA may suffer repeated episodes of intense pain, paralysis, and sensory disturbances in an affected limb. The onset of HNA is at birth or later in childhood with prognosis for recovery usually favorable; however, persons with HNA may have permanent residual neurological dysfunction following attack(s). Episodes are often
Dallo, Florence J; Schwartz, Kendra; Ruterbusch, Julie J; Booza, Jason; Williams, David R
The objectives of this study were to: (1) calculate age-specific and age-adjusted cause-specific mortality rates for Arab Americans; and (2) compare these rates with those for blacks and whites. Mortality rates were estimated using Michigan death certificate data, an Arab surname and first name list, and 2000 U.S. Census data. Age-specific rates, age-adjusted all-cause and cause-specific rates were calculated. Arab Americans (75+) had higher mortality rates than whites and blacks. Among men, all-cause and cause-specific mortality rates for Arab Americans were in the range of whites and blacks. However, Arab American men had lower mortality rates from cancer and chronic lower respiratory disease compared to both whites and blacks. Among women, Arab Americans had lower mortality rates from heart disease, cancer, stroke, and diabetes than whites and blacks. Arab Americans are growing in number. Future study should focus on designing rigorous separate analyses for this population.
At the University of Michigan, biofluid mechanics is taught in the Department of Biomedical Engineering with cross-listing in Mechanical Engineering. The course has evolved over 25 years and serves advanced undergraduates and graduate students. The course description is as follows: BiomedE/MechE 476 Biofluid Mechanics. CATALOG DESCRIPTION: This is an intermediate level fluid mechanics course which uses examples from biotechnology processes and physiologic applications including cellular, cardiovascular, respiratory, ocular, renal, orthopedic, and gastrointestinal systems. COURSE TOPICS: 1. Dimensional analysis (gastrointestinal, renal) 2. Approximation methods, numerical methods (biotechnology, respiratory) 3. Particle kinematics in Eulerian and Lagrangian references frames (biotechnology, respiratory) 4. Conservation of mass and momentum 5. Constitutive equations (blood, mucus) 6. Kinematic and stress boundary conditions: rigid, flexible, porous (cardio-pulmonary, cellular) 7. Surface tension phenomena (pulmonary, ocular) 8. Flow and wave propagation in flexible tubes (cardio-pulmonary) 9. Oscillatory and pulsatile flows (cardio-pulmonary, orthopedic) 10. High Reynolds number flows (cardio-pulmonary) 11. Low Reynolds number flows (biotechnology, cellular, vascular) 12. Lubrication theory (vascular, orthopedic) 13. Flow in poroelastic media (orthopedic, pulmonary, ocular) 14. Video presentations of laboratory experiments.
Full Text Available Background: Complication of diabetes mellitus includes peripheral neuropathy which causes ischemic foot ulceration. Hyperglycemia and insulin resistance may accelerate the development of diabetic peripheral neuropathy. Objective: To assess the glycaemic status and insulin resistance for development of peripheral neuropathy in type 2 diabetes mellitus. Methods: This control case control study was conducted in the Department of Physiology, Dhaka Medical College, Dhaka from July 2014 to June 2015. A total number of 150 Type 2 diabetic patients of both sexes were selected with age ranging 40 to 50 years. Among them, 75 patients with peripheral neuropathy were included in study group and 75 patients without peripheral neuropathy were control. For evaluation of glycaemic status, fasting serum glucose (FSG, Glycosylated hemoglobin (HbA1c and to calculate insulin resistance by homeostatic model assessment for insulin resistance (HOMA-IR, fasting serum insulin (FSI, were estimated. For statistical analysis, unpaired Student’s ‘t’ test was done. Results: In this study, significant increase in FSG, HbA1c, FSI, HOMA-IR were found in diabetic subjects with peripheral neuropathy in comparison to control group. Conclusion: From the study results, it is concluded that poor glycaemic control and greater insulin resistance may be associated with diabetic peripheral neuropathy.
Witzel, Ini-Isabée; Jelinek, Herbert F.; Khalaf, Kinda; Lee, Sungmun; Khandoker, Ahsan H.; Alsafar, Habiba
Type 2 diabetes mellitus (T2DM) is a global public health problem of epidemic proportions, with 60–70% of affected individuals suffering from associated neurovascular complications that act on multiple organ systems. The most common and clinically significant neuropathies of T2DM include uremic neuropathy, peripheral neuropathy, and cardiac autonomic neuropathy. These conditions seriously impact an individual’s quality of life and significantly increase the risk of morbidity and mortality. Although advances in gene sequencing technologies have identified several genetic variants that may regulate the development and progression of T2DM, little is known about whether or not the variants are involved in disease progression and how these genetic variants are associated with diabetic neuropathy specifically. Significant missing heritability data and complex disease etiologies remain to be explained. This article is the first to provide a review of the genetic risk variants implicated in the diabetic neuropathies and to highlight potential commonalities. We thereby aim to contribute to the creation of a genetic-metabolic model that will help to elucidate the cause of diabetic neuropathies, evaluate a patient’s risk profile, and ultimately facilitate preventative and targeted treatment for the individual. PMID:26074879
Rajabally, Yusuf A; Stettner, Mark; Kieseier, Bernd C; Hartung, Hans-Peter; Malik, Rayaz A
Distal symmetric polyneuropathy (DSPN) is the most common neuropathy to occur in diabetes mellitus. However, patients with diabetes can also develop inflammatory neuropathies, the most common and most treatable of which is chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Whether diabetes is a risk factor for CIDP remains under debate. Early studies suggested that patients with diabetes were at increased risk of CIDP, but epidemiological studies failed to confirm the association, and subsequent data have re-opened the debate. Inadequate interpretation of investigations and differentials between CIDP and other neuropathies that can occur in diabetes, such as DSPN, diabetic radiculoplexus neuropathies and vasculitic multiple mononeuropathy, might mean that CIDP is under-recognized. Despite a response rate of >80% to first-line therapies for CIDP in patients with or without diabetes, those with diabetes often present with greater disability owing to late referral and axonal pathology attributed to DSPN. The increasing worldwide prevalence of diabetes creates an urgent need to improve identification of potentially treatable neuropathies, such as CIDP. In this Review, we consider the features of CIDP in patients with diabetes, and discuss how these features can be used to differentiate the condition from other neuropathies. We also review the management options for CIDP and other inflammatory neuropathies in patients with diabetes.
Areti, Aparna; Yerra, Veera Ganesh; Komirishetty, Prashanth; Kumar, Ashutosh
Peripheral neuropathies are a group of diseases characterized by malfunctioning of peripheral nervous system. Neuropathic pain, one of the core manifestations of peripheral neuropathy remains as the most severe disabling condition affecting the social and daily routine life of patients suffering from peripheral neuropathy. The current review is aimed at unfolding the possible role of mitochondrial dysfunction in peripheral nerve damage and to discuss on the probable therapeutic strategies against neuronal mitotoxicity. The article also highlights the therapeutic significance of maintaining a healthy mitochondrial environment in neuronal cells via pharmacological management in context of peripheral neuropathies. Aberrant cellular signaling coupled with changes in neurotransmission, peripheral and central sensitization are found to be responsible for the pathogenesis of variant toxic neuropathies. Current research reports have indicated the possible involvement of mitochondria mediated redox imbalance as one of the principal causes of neuropathy aetiologies. In addition to imbalance in redox homeostasis, mitochondrial dysfunction is also responsible for alterations in physiological bioenergetic metabolism, apoptosis and autophagy pathways. In spite of various etiological factors, mitochondrial dysfunction has been found to be a major pathomechanism underlying the neuronal dysfunction associated with peripheral neuropathies. Pharmacological modulation of mitochondria either directly or indirectly is expected to yield therapeutic relief from various primary and secondary mitochondrial diseases.
Singh, Randhir; Kishore, Lalit; Kaur, Navpreet
Diabetic neuropathy is a heterogeneous group of disorders with extremely complex pathophysiology and affects both somatic and autonomic components of the nervous system. Neuropathy is the most common chronic complication of diabetes mellitus. Metabolic disruptions in the peripheral nervous system, including altered protein kinase C activity, and increased polyol pathway activity in neurons and Schwann cells resulting from hyperglycemia plays a key role in the development of diabetic neuropathy. These pathways are related to the metabolic and/or redox state of the cell and are the major source of damage. Activation of these metabolic pathways leads to oxidative stress, which is a mediator of hyperglycemia induced cell injury and a unifying theme for all mechanisms of diabetic neuropathy. The therapeutic intervention of these metabolic pathways is capable of ameliorating diabetic neuropathy but therapeutics which target one particular mechanism may have a limited success. Available therapeutic approaches are based upon the agents that modulate pathogenetic mechanisms (glycemic control) and relieve the symptoms of diabetic neuropathy. This review emphasizes the pathogenesis, presently available therapeutic approaches and future directions for the management of diabetic neuropathy.
Malik, R A
As of March 2016, we continue to advocate the diagnosis of diabetic neuropathy using a simple foot examination or monofilament, which identifies only those with severe neuropathy and hence risk of foot ulceration. Given the fact that the 5-year mortality rate of diabetic patients with foot ulceration is worse than that of most common cancers, surely we should be identifying patients at an earlier stage of neuropathy to prevent its progression to a stage with such a high mortality? Of course, we lament that there is no licensed treatment for diabetic neuropathy. Who is to blame? As researchers and carers, we have a duty of care to our patients with diabetic neuropathy. So, we have to look forward not backwards, and move away from our firmly entrenched views on the design and conduct of clinical trials for diabetic neuropathy. Relevant organizations such as Neurodiab, the American Diabetes Association and the Peripheral Nerve Society have to acknowledge that they cannot continue to endorse a bankrupt strategy. The FDA needs an open and self-critical dialogue with these organizations, to give pharmaceutical companies at least a fighting chance to deliver effective new therapies for diabetic neuropathy.
Donadio, Vincenzo; Incensi, Alex; Giannoccaro, Maria Pia; Cortelli, Pietro; Di Stasi, Vitantonio; Pizza, Fabio; Jaber, Masen Abdel; Baruzzi, Agostino; Liguori, Rocco
Skin biopsy has gained widespread use for the diagnosis of somatic small-fiber neuropathy, but it also provides information on sympathetic fiber morphology. We aimed to ascertain the diagnostic accuracy of skin biopsy in disclosing sympathetic nerve abnormalities in patients with autonomic neuropathy. Peripheral nerve fiber autonomic involvement was confirmed by routine autonomic laboratory test abnormalities. Punch skin biopsies were taken from the thigh and lower leg of 28 patients with various types of autonomic neuropathy for quantitative evaluation of skin autonomic innervation. Results were compared with scores obtained from 32 age-matched healthy controls and 25 patients with somatic neuropathy. The autonomic cutoff score was calculated using the receiver operating characteristic curve analysis. Skin biopsy disclosed a significant autonomic innervation decrease in autonomic neuropathy patients versus controls and somatic neuropathy patients. Autonomic innervation density was abnormal in 96% of patients in the lower leg and in 79% of patients in the thigh. The abnormal findings disclosed by routine autonomic tests ranged from 48% to 82%. These data indicate the high sensitivity and specificity of skin biopsy in detecting sympathetic abnormalities; this method should be useful for the diagnosis of autonomic neuropathy, together with currently available routine autonomic testing.
Asif, Naiyer; Singh, Paras Nath; Hossain, Mohd Mobarak
Introduction The post-menopausal phase is characterized by a decline in the serum oestrogen and progesterone levels. This phase is also associated with higher incidence of peripheral neuropathy. Aim To explore the relationship between the peripheral motor nerve status and serum oestrogen and progesterone levels through assessment of Motor Nerve Conduction Velocity (MNCV) in post-menopausal women with peripheral neuropathy. Materials and Methods This cross-sectional study was conducted at Jawaharlal Nehru Medical College during 2011-2013. The study included 30 post-menopausal women with peripheral neuropathy (age: 51.4±7.9) and 30 post-menopausal women without peripheral neuropathy (control) (age: 52.5±4.9). They were compared for MNCV in median, ulnar and common peroneal nerves and serum levels of oestrogen and progesterone estimated through enzyme immunoassays. To study the relationship between hormone levels and MNCV, a stepwise linear regression analysis was done. Results The post-menopausal women with peripheral neuropathy had significantly lower MNCV and serum oestrogen and progesterone levels as compared to control subjects. Stepwise linear regression analysis showed oestrogen with main effect on MNCV. Conclusion The findings of the present study suggest that while the post-menopausal age group is at a greater risk of peripheral neuropathy, it is the decline in the serum estrogen levels which is critical in the development of peripheral neuropathy. PMID:28208850
Kazamel, Mohamed; Dyck, Peter J
Diabetes mellitus is among the most common causes of peripheral neuropathy worldwide. Sensory impairment in diabetics is a major risk factor of plantar ulcers and neurogenic arthropathy (Charcot joints) causing severe morbidity and high health-care costs. To discuss the different patterns of sensory alterations in diabetic neuropathies and their anatomical basis. Literature review. Review of the literature discussing different patterns of sensory impairment in diabetic neuropathies. The different varieties of diabetic neuropathies include typical sensorimotor polyneuropathy (lower extremity predominant, length-dependent, symmetric, sensorimotor polyneuropathy presumably related to chronic hyperglycemic exposure, and related metabolic events), entrapment mononeuropathies, radiculoplexus neuropathies related to immune inflammatory ischemic events, cranial neuropathies, and treatment-related neuropathies (e.g. insulin neuritis). None of these patterns are unique for diabetes, and they can occur in nondiabetics. Sensory alterations are different among these prototypic varieties and are vital in diagnosis, following course, treatment options, and follow-up of treatment effects. Diabetic neuropathies can involve any segment of peripheral nerves from nerve roots to the nerve endings giving different patterns of abnormal sensation. It is the involvement of small fibers that causes positive sensory symptoms like pain early during the course of disease, bringing subjects to physician's care. This article emphasizes on the fact that diabetic neuropathies are not a single entity. They are rather different varieties of conditions with more or less separate pathophysiological mechanisms and anatomical localization. Clinicians should keep this in mind when assessing patients with diabetes on the first visit or follow-up. © The International Society for Prosthetics and Orthotics 2014.
Torrey, M S
The report is a synoptic review of data collected over the past twenty years on the chemistry of Lake Michigan. Changes in water quality and sediment chemistry, attributable to cultural and natural influences, are considered in relation to interacting processes and factors controlling the distribution and concentration of chemical substances within the Lake. Temperature, light, and mixing processes are among the important natural influences that affect nutrient cycling, dispersal of pollutants, and fate of materials entering the Lake. Characterization of inshore-offshore and longitudinal differences in chemical concentrations and sediment chemistry for the main body of the Lake is supplemented by discussion of specific areas such as Green Bay and Grand Traverse Bay. Residues, specific conductance, dissolved oxygen, major and trace nutrients, and contaminants are described in the following context: biological essentiality and/or toxicity, sources to the Lake, concentrations in the water column and sediments, chemical forms, seasonal variations and variation with depth. A summary of existing water quality standards, statutes, and criteria applicable to Lake Michigan is appended.
This report characterizes the bird life found in 100 counties of the four states peripheral to Lake Michigan. It discusses major habitats (the Lake Michigan shoreline, inland lakes, rivers and streams, marshes, fields and open spaces, and woodlots) and associates specific birds with habitats according to preferences for space and food. It also discusses the special attributes of state parks and lakeshores, refuges and sanctuaries, and other special areas which are attractive to avifauna. Patterns of historical occurrence and abundance, and the influence of pesticides and pollution, disease, and hunting pressure are explored to place present occurrence in a modern perspective. Migration patterns are discussed to explain increases and decreases which occur in nonresident avifauna of the Basin. The distribution and habits of birds that occur regularly in the Basin are described in an annotated list; a more complete list is presented in a table which encapsulates data for rapid and convenient reference. Separate sections deal with extinct, extirpated, and introduced species, and with endangered, threatened, and declining species.
Brewer, Jamie R; Morrison, Gladys; Dolan, M Eileen; Fleming, Gini F
As there are increasing numbers of cancer survivors, more attention is being paid to the long term unwanted effects patients may experience as a result of their treatment and the impact these side effects can have on their quality of life. Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common long-term toxicities from chemotherapy. In this review we will briefly review the clinical presentation, evaluation and management of chemotherapy-induced peripheral neuropathy, with a focus on CIPN related to platinum and taxane agents. We will then discuss current clinical models of peripheral neuropathy and ongoing research to better understand CIPN and develop potential treatment options.
Hernández-Beltrán, Natalia; Moreno, Carlos B; Gutiérrez-Álvarez, Angela María
Diabetes is a metabolic disease affecting approximately 300 million people worldwide. Neuropathy is one of its frequent complications, and may affect sensory, motor, and autonomic nerves. Its pathophysiology has not fully been elucidated. Several hypotheses have been proposed, and mitochondria have been suggested to play a significant role. This article reviews the mechanisms involved in mitochondrial dysfunction and development of diabetic neuropathy, consisting mainly of oxidative and inflammatory stress, changes in intracellular calcium regulation, apoptotic processes, and changes in mitochondrial structure and function that may lead to development of diabetic neuropathy.
Full Text Available Sphenoid sinus mucocele comprises only 2% of all paranasal sinus mucoceles. In literature, there is a case report on sphenoidal mucocele causing bilateral optic neuropathy, with unilateral partial recovery and cranial nerve palsy, but we did not come across any literature with bilateral optic neuropathy and ophthalmoplegia together caused by spheno-ethmoidal mucocele. We present such a rare case of spheno-ethmoidal mucocele causing bilateral optic neuropathy and unilateral sixth nerve palsy who had postsurgery, unilateral good vision recovery, and complete resolution of sixth nerve palsy.
Selvakumar, Ambika; Mahalaxmi, Balasubramanyam; Ananth, V; Gautam, Cugati
Sphenoid sinus mucocele comprises only 2% of all paranasal sinus mucoceles. In literature, there is a case report on sphenoidal mucocele causing bilateral optic neuropathy, with unilateral partial recovery and cranial nerve palsy, but we did not come across any literature with bilateral optic neuropathy and ophthalmoplegia together caused by spheno-ethmoidal mucocele. We present such a rare case of spheno-ethmoidal mucocele causing bilateral optic neuropathy and unilateral sixth nerve palsy who had postsurgery, unilateral good vision recovery, and complete resolution of sixth nerve palsy.
Wasserman, T.H.; Nelson, J.S.; VonGerichten, D.
The dose limiting toxicity of the nitroimidazole radiosensitizers is peripherial neuropathy. Improved pharmacology of newer drugs has eliminated the encephalopathy. Peripheral neuropathies are predominently mild to moderate paresthesias of both hands and feet. Subjective changes occur with or without minimal objective changes on neurologic exam. All of the neuropathies occurred within 30 days of the last drug dose and are of varible duration. Sural nerve biopsies from patients indicate progressive axonal degeneration affecting both large and small caliber myelinated fibers. Axonal damage appears to be more severe in the distal portion of the nerves. More data are needed for correlation of clinical and pathological changes.
Nisar, M; Watkin, S W; Bucknall, R C; Agnew, R A
Mycobacterium kansasii was isolated from an area of cavitating pneumonia in a man with rheumatoid arthritis. Standard antituberculosis treatment, including isoniazid 300 mg daily, had to be stopped because of peripheral neuropathy. The patient, a slow acetylator, subjectively deteriorated despite withdrawal of isoniazid and treatment with pyridoxine 150 mg daily. Improvement occurred only after the pyridoxine had also been withdrawn. Pyridoxine may cause peripheral neuropathy and this case illustrates the need for caution in the use of this vitamin in the prevention and treatment of isoniazid induced peripheral neuropathy.
John Jhon. K
Full Text Available Giant axonal neuropathy is a rate disorder with an autosomal recessive inheritance. It should be differentiated from toxic neuropathies, and hereditary degenerative disorders of nervous system like Friedreich′s ataxia and HMSN. Thick curly hair, though may not be present always is a useful clinical clue to identify cases. Prognosis is generally poor though course of the illness is variable. We report here a clinically and hisopathologically characteristic familial case of giant axonal neuropathy, which occurred in a 17-year-old boy, and his 21-year-old sister.
Chevrollier, Arnaud; Guillet, Virginie; Loiseau, Dominique; Gueguen, Naïg; de Crescenzo, Marie-Anne Pou; Verny, Christophe; Ferre, Marc; Dollfus, Hélène; Odent, Sylvie; Milea, Dan; Goizet, Cyril; Amati-Bonneau, Patrizia; Procaccio, Vincent; Bonneau, Dominique; Reynier, Pascal
Hereditary optic neuropathies are heterogeneous diseases characterized by the degeneration of retinal ganglion cells leading to optic nerve atrophy and impairment of central vision. We found a common coupling defect of oxidative phosphorylation in fibroblasts of patients affected by autosomal dominant optic atrophy (mutations of OPA1), autosomal dominant optic atrophy associated with cataract (mutations of OPA3), and Leber's hereditary optic neuropathy, a disorder associated with point mutations of mitochondrial DNA complex I genes. Interestingly, the energetic defect was significantly more pronounced in Leber's hereditary optic neuropathy and autosomal dominant optic atrophy patients with a more complex phenotype, the so-called plus phenotype.
O'Neill, Evelyn C; Mackey, David A; Connell, Paul P; Hewitt, Alex W; Danesh-Meyer, Helen V; Crowston, Jonathan G
Hereditary optic neuropathies are a prominent cause of blindness in both children and adults. The disorders in this group share many overlapping clinical characteristics, including morphological changes that occur at the optic nerve head. Accurate and prompt clinical diagnosis, supplemented with imaging when indicated, is essential for optimum management of the relevant optic neuropathy and appropriate counseling of the patient on its natural history. Patient history, visual field assessment, optic disc findings and imaging are the cornerstones of a correct diagnosis. This Review highlights the characteristic optic nerve head features that are common to the various hereditary optic neuropathies, and describes the features that enable the conditions to be differentiated.
Callizot, N; Warter, J M; Poindron, P
Sensory neuropathies are frequently associated with diabetes or with antimitotic treatments in humans suffering from cancer, and are in this case the most important limitation to the use of antimitotic drugs. For this reason, there is a need to establish and validate animal models of sensory neuropathies that could be routinely used, together with the already known models, for studying and evaluating the effects of putative neuroprotective compounds. In the present study, we prove by behavioral and electromyographical analyses that (a) it is possible to induce a nonlethal, exclusively sensory, reversible neuropathy by intoxicating rats with large amounts of pyridoxine, using a new schedule of intoxication; (b) 4-methylcatechol, a drug known to induce nerve growth factor synthesis, improves the clinical status of pyridoxine-intoxicated animals, shortens the duration of the disease, and restores the morphological integrity of the sensory fibers. Owing to its mode of installation and its clinical features, we propose that this model be used as an additional model for preclinical studies of neuroprotective drugs.
Sala, Anca L.; Dreyer, Elizabeth F. C.; Aku-Leh, Cynthia; Jones, Timothy; Nees, John A.; Smith, Arlene
The 2015 International Year of Light created a wonderful opportunity to bring light and optics events and activities to people of all ages and occupations in Michigan. A large spectrum of events took place; from events held in schools, colleges, and universities targeting various groups of students, to events associated with festivals attended by large crowds. The latter included the Ann Arbor Summer Festival held in June and the Flint Back-to-the-Bricks Festival in August. All events included interactive activities where participants learned hands-on about optics and photonics phenomena and applications. Original demonstrations and kits were developed by the Ann Arbor OSA Local Section and the Optics Society at the University of Michigan, the joint OSA/SPIE student chapter, for use during the events. The activities were funded through the student chapter's SPIE grant for IYL outreach events and corporate sponsorships. Under the name Michigan Light Project, these groups along with local technology enthusiasts and science clubs delivered several events across Michigan. Other events took place throughout the year in Mid-Michigan through the efforts of faculty and students in the Photonics and Laser Technology program at Baker College of Flint. The outreach events targeted students in K-12. Teachers, counselors, and parents also learned about the importance of optics and photonics in society. The activities developed will continue this year and in the future. The paper will provide details on the completed events and activities along with tips for implementing similar activities and outreach partnerships in other areas.
Zimmerman, Jerome W.
Water quality of streams tributary to Lakes Superior and Michigan was analyzed for 142 stations on 99 streams tributary to Lake Superior and 83 stations on 56 streams tributary to Lake Michigan during 1962-65. Concentrations of aluminum, copper, and iron were not affected greatly by flow or season. Magnesium, calcium, chlorides, total alkalinity, total hardness, and conductivity varied with the flow, temperature, and season; the lowest values were during the spring runoff and heavy rains, and the highest were during low water in late summer and the colder periods of winter. Concentrations of nitrate, silica, and sulfates were lowest in the spring and summer. Concentrations of tanninlike and ligninlike compounds were highest during the spring runoff and other high-water periods, and were lowest during freezeup when surface runoff was minimal. The pH values were highest from June to September and lowest during the spring runoff. Phenolphthalein alkalinity was detected primarily in the summer and coincided occasionally with low flows just before the spring thaw. Total hardness usually was lower in streams tributary to Lake Superior than in streams tributary to Lake Michigan. The total hardness was higher in the streams in Wisconsin than in the streams in Michigan along the west shore of Lake Michigan. It was lowest in the northernmost streams. The water quality of the streams in an area was related to the geological characteristics of the land.
Cunningham, Alisa F.; Erisman, Wendy; Looney, Shannon E.
This fact sheet presents a snapshot of important facts from "Higher Education in Michigan: Overcoming Challenges to Expand Access," which examines access to postsecondary degrees and institutions in underserved regions of Michigan. [For the full report, see ED501512.
Mendon, Vrushali V. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Zhao, Mingjie [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Taylor, Zachary T. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Poehlman, Eric A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
The 2015 IECC provides cost-effective savings for residential buildings in Michigan. Moving to the 2015 IECC from the 2009 IECC base code is cost-effective for residential buildings in all climate zones in Michigan.
... National Park Service Notice of Inventory Completion: Western Michigan University, Anthropology Department.... Western Michigan University, Department of Anthropology has completed an inventory of human remains and..., Department of Anthropology. Disposition of the human remains and associated funerary objects to the...
... National Park Service Notice of Inventory Completion: Western Michigan University, Anthropology Department..., Anthropology Department, has completed an inventory of human remains and associated funerary objects, in... associated funerary objects may contact the Western Michigan University, Anthropology Department....
... Anthropology, Kalamazoo, MI AGENCY: National Park Service, Interior. ACTION: Notice. SUMMARY: Western Michigan University, Department of Anthropology, has completed an inventory of human remains and associated funerary... may contact Western Michigan University, Department of Anthropology. Disposition of the human...
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... National Park Service Notice of Inventory Completion: Western Michigan University, Anthropology Department... Michigan University, Anthropology Department, Kalamazoo, MI. The human remains and associated funerary... and associated funerary objects should contact LouAnn Wurst, Department of Anthropology,...
... Inventory Completion: Western Michigan University, Anthropology Department, Kalamazoo, MI AGENCY: National..., Anthropology Department, Kalamazoo, MI. The human remains and associated funerary objects were removed from... physical anthropologist in the Anthropology Department at Western Michigan University, studied the...
... National Park Service Notice of Inventory Completion: Western Michigan University, Anthropology Department..., Department of Anthropology, has completed an inventory of human remains, in consultation with the appropriate... affiliated with the human remains may contact the Western Michigan University, Department of...
... From the Federal Register Online via the Government Publishing Office ENVIRONMENTAL PROTECTION AGENCY 40 CFR Part 52 Approval and Promulgation of Air Quality Implementation Plans; Michigan; PSD... significant deterioration (PSD) construction permit program in Michigan. As required by the conditional...
... From the Federal Register Online via the Government Publishing Office ENVIRONMENTAL PROTECTION AGENCY Public Water System Supervision Program Approval for the State of Michigan AGENCY: Environmental... has tentatively approved five revisions to the State of Michigan's public water system...
CHICAGO -- The U.S Environmental Protection Agency today announced that Central Michigan University in Mt. Pleasant, Michigan, has received a $10 million Great Lakes Restoration Initiative grant to monitor coastal wetlands around the Great Lakes basin over
Brummett, Chad M; Bakshi, Rishi R; Goesling, Jenna; Leung, Daniel; Moser, Stephanie E; Zollars, Jennifer W; Williams, David A; Clauw, Daniel J; Hassett, Afton L
We developed the Michigan Body Map (MBM) as a self-report measure to assess body areas where chronic pain is experienced and to specifically quantify the degree of widespread body pain when assessing for centralized pain features (eg, fibromyalgia-like presentation). A total of 402 patients completed the measure in 5 distinct studies to support the validation of the original and a revised version of the MBM. Administration is rapid 39 to 44 seconds, and errors for the original MBM were detected in only 7.2% of the possible body areas. Most errors underestimated the number of painful areas or represented confusion in determining the right vs left side. The MBM was preferred (P = 0.013) and felt to better depict pain location (P = 0.001) when compared with the Widespread Pain Index checklist of the 2011 Fibromyalgia Survey Criteria, but participants did not express any preference between the MBM and Brief Pain Inventory body map. Based on the data from the first 3 studies, a revised version of the MBM was created including a front and back body image and improved guidance on right-sidedness vs left. The revised MBM was preferred when compared with the original and was more accurate in depicting painful body areas (P = 0.004). Furthermore, the revised MBM showed convergent and discriminant validity with other self-report measures of pain, mood, and function. In conclusion, the MBM demonstrated utility, reliability, and construct validity. This new measure can be used to accurately assess the distribution of pain or widespread bodily pain as an element of the fibromyalgia survey score.
Gueven, Nuri; Nadikudi, Monila; Daniel, Abraham; Chhetri, Jamuna
Many reports have illustrated a tight connection between vision and mitochondrial function. Not only are most mitochondrial diseases associated with some form of vision impairment, many ophthalmological disorders such as glaucoma, age-related macular degeneration and diabetic retinopathy also show signs of mitochondrial dysfunction. Despite a vast amount of evidence, vision loss is still only treated symptomatically, which is only partially a consequence of resistance to acknowledge that mitochondria could be the common denominator and hence a promising therapeutic target. More importantly, clinical support of this concept is only emerging. Moreover, only a few drug candidates and treatment strategies are in development or approved that selectively aim to restore mitochondrial function. This review rationalizes the currently developed therapeutic approaches that target mitochondrial function by discussing their proposed mode(s) of action and provides an overview on their development status with regards to optic neuropathies.
Cacace, Anthony T; Pinheiro, Joaquim M B
'Auditory neuropathy' (AN), the term used to codify a primary degeneration of the auditory nerve, can be linked directly or indirectly to mitochondrial dysfunction. These observations are based on the expression of AN in known mitochondrial-based neurological diseases (Friedreich's ataxia, Mohr-Tranebjærg syndrome), in conditions where defects in axonal transport, protein trafficking, and fusion processes perturb and/or disrupt mitochondrial dynamics (Charcot-Marie-Tooth disease, autosomal dominant optic atrophy), in a common neonatal condition known to be toxic to mitochondria (hyperbilirubinemia), and where respiratory chain deficiencies produce reductions in oxidative phosphorylation that adversely affect peripheral auditory mechanisms. This body of evidence is solidified by data derived from temporal bone and genetic studies, biochemical, molecular biologic, behavioral, electroacoustic, and electrophysiological investigations.
Zhang, A-Mei; Yao, Yong-Gang
Leber hereditary optic neuropathy (LHON; MIM 535000) is one of the most common mitochondrial diseases, with a clinical manifestation of painless, acute or sub-acute bilateral visual loss in young adults leading to blindness and central scotoma. Over 95% of LHON patients were caused by one of three primary mtDNA mutations (m.11778G>A, m.3460G>A and m.14484T>C). Incomplete penetrance and gender bias are two riddles of this disease. Here we summarized recent research progress of LHON, with a focus on the molecular pathogenic mechanisms, clinical features, in vitro experiments and animal models, and prevention and treatment of LHON. In particular, we presented the main findings and challenges in our recent efforts to decipher genetic susceptibility and mechanism of LHON in Chinese patients.
Idebenone is a rapidly absorbed, safe and well-tolerated drug and is currently the only clinically proven treatment option for Leber's hereditary optic neuropathy (LHON) patients. Idebenone (Raxone®) is approved by the European Medicines Agency for the treatment of LHON and has been available on the European market since 2015. Due to its molecular mode of action of bypassing the defective mitochondrial complex I, idebenone leads to improved energy supply and a functional recovery of retinal ganglion cells during the acute stage of the disease, thereby preventing further vision loss and promoting recovery of vision. Thus, commencing treatment shortly after the onset of symptoms is likely to have the best therapeutic effect, a hypothesis that is supported by the available clinical data.
Arsalan, Rabeeya; Sabzwari, Saniya
Isoniazid though a very effective treatment for tuberculosis can cause severe motor-dominant neuropathy which can be reversible with pyridoxine supplementation. A 45-year-old female diagnosed with psoas abscess, culture positive for mycobacterium tuberculosis, was started on anti- tuberculous treatment with four drugs, including isoniazid at a dose of 5 mg/kg/day. Three months later she developed severe motor weakness of lower limbs with loss of ankle and knee reflexes. She was treated with vitamin B6 injections and isoniazid treatment was continued. Her motor weakness gradually improved in a few months, but mild sensory impairment persisted even after two years. There is need for vigilance regarding neurological effects of isoniazid in seemingly low-risk individuals in whom development of symptoms should raise the suspicion about slow acetylator status. Timely therapeutic intervention with high-dose vitamin B6 can reduce the long-term morbidity associated with this easily reversible condition.
Scott, K; Zeris, S; Kothari, M J
Polyneuropathy related to decreased levels of Vitamin B6 are well known. In contrast, the association between elevated levels of pyridoxine and neuropathy is not well described. This study is a retrospective review of patients in our neuromuscular clinic that were found to have elevated B6 levels. Twenty-six patients were found to have elevated serum B6 levels. The mean B6 level was 68.8 ng/ml. Twenty patients (76.9%) reported daily vitamin use. Twenty-one patients (80.8%) reported only sensory complaints. The most common symptoms reported were numbness (96%), burning pain (49.9%), tingling (57.7%), balance difficulties (30.7%), and weakness (7.8%). Nine (out of 26) had an abnormal EMG/NCS. Eight patients had an abnormal quantitative sensory study. We conclude that elevated pyridoxine levels should be considered in the differential diagnosis of any sensory or sensorimotor polyneuropathy.
Head, Kathleen A
Peripheral neuropathy (PN), associated with diabetes, neurotoxic chemotherapy, human immunodeficiency virus (HIV)/antiretroviral drugs, alcoholism, nutrient deficiencies, heavy metal toxicity, and other etiologies, results in significant morbidity. Conventional pain medications primarily mask symptoms and have significant side effects and addiction profiles. However, a widening body of research indicates alternative medicine may offer significant benefit to this patient population. Alpha-lipoic acid, acetyl-L-carnitine, benfotiamine, methylcobalamin, and topical capsaicin are among the most well-researched alternative options for the treatment of PN. Other potential nutrient or botanical therapies include vitamin E, glutathione, folate, pyridoxine, biotin, myo-inositol, omega-3 and -6 fatty acids, L-arginine, L-glutamine, taurine, N-acetylcysteine, zinc, magnesium, chromium, and St. John's wort. In the realm of physical medicine, acupuncture, magnetic therapy, and yoga have been found to provide benefit. New cutting-edge conventional therapies, including dual-action peptides, may also hold promise.
Mohite, Abhijit Anand; Agius-Fernandez, Adriana
Chikungunya fever is a vector borne virus that typically causes a self-limiting systemic illness with fever, skin rash and joint aches 2 weeks after infection. We present the case of a 69-year-old woman presenting with an acute unilateral optic neuropathy as a delayed complication of Chikungunya virus (CHIKV) infection contracted during a recent trip to the West Indies. She presented to our ophthalmology department with acute painless visual field loss in the right eye and a recent flu-like illness. She was found to have a right relative afferent pupillary defect (RAPD) with unilateral optic disc swelling. Serology confirmed recent CHIKV infection. Treatment with intravenous methylprednisolone was delayed while awaiting MRI scans and serology results. At 5-month follow-up, there was a persistent right RAPD and marked optic atrophy with a corresponding inferior scotoma in the visual field. 2015 BMJ Publishing Group Ltd.
Lupo, Vincenzo; Aguado, Carmen; Knecht, Erwin; Espinós, Carmen
Distal hereditary motor neuropathies (dHMN) are a group of rare hereditary neuromuscular disorders characterized by an atrophy that affects peroneal muscles in the absence of sensory symptoms. To date, 23 genes are thought to be responsible for dHMN, four of which encode chaperones: DNAJB2, which encodes a member of the HSP40/DNAJ co-chaperone family; and HSPB1, HSPB3, and HSPB8, encoding three members of the small heat shock protein family. While around 30 different mutations in HSPB1 have been identified, the remaining three genes are altered in many fewer cases. Indeed, a mutation of HSPB3 has only been described in one case, whereas a few cases have been reported carrying mutations in DNAJB2 and HSPB8, most of them caused by a founder c.352+1G>A mutation in DNAJB2 and by mutations affecting the K141 residue in the HSPB8 chaperone. Hence, their rare occurrence makes it difficult to understand the pathological mechanisms driven by such mutations in this neuropathy. Chaperones can assemble into multi-chaperone complexes that form an integrated chaperone network within the cell. Such complexes fulfill relevant roles in a variety of processes, such as the correct folding of newly synthesized proteins, in which chaperones escort them to precise cellular locations, and as a response to protein misfolding, which includes the degradation of proteins that fail to refold properly. Despite this range of functions, mutations in some of these chaperones lead to diseases with a similar clinical profile, suggesting common pathways. This review provides an overview of the genetics of those dHMNs that share a common disease mechanism and that are caused by mutations in four genes encoding chaperones: DNAJB2, HSPB1, HSPB3, and HSPB8.
Full Text Available Distal hereditary motor neuropathies (dHMN comprise a group of rare hereditary neuromuscular disorders characterized by a peroneal muscular atrophy without sensory symptoms. To date twenty-three genes for dHMN have been reported and four of them encode for chaperones: DNAJB2, which encodes a member of the HSP40/DNAJ co-chaperone family, and HSPB1, HSPB3 and HSPB8, which encode three members of the family of small heat shock proteins. Except for HSPB1, with around thirty different mutations, the remaining three genes comprise a much low number of cases. Thus, only one case has been described caused by an HSPB3 mutation, whereas few DNAJB2 and HSPB8 cases are known, most of them caused by a founder c.352+1G>A mutation in DNAJB2 and by mutations affecting the hot spot K141 residue of the HSPB8 chaperone. This low number of cases makes it difficult to understand the pathomechanism underlying the neuropathy. Chaperones can assemble in multi-chaperone complexes forming an integrative chaperone network in the cell, which plays relevant cellular roles in a variety of processes such as the correct folding of newly synthesized proteins, their escort to their precise cellular locations to form functional proteins and complexes and the response to protein misfolding, including the degradation of proteins that fail to refold properly. Despite of this variety of functions, mutations in some of them lead to diseases with a similar clinical picture, suggesting common pathways. This review gives an overview of the genetics of dHMNs caused by mutations in four genes, DNAJB2, HSPB1, HSPB3 and HSPB8, which encode chaperones and show a common disease mechanism.
Lupo, Vincenzo; Aguado, Carmen; Knecht, Erwin; Espinós, Carmen
Distal hereditary motor neuropathies (dHMN) are a group of rare hereditary neuromuscular disorders characterized by an atrophy that affects peroneal muscles in the absence of sensory symptoms. To date, 23 genes are thought to be responsible for dHMN, four of which encode chaperones: DNAJB2, which encodes a member of the HSP40/DNAJ co-chaperone family; and HSPB1, HSPB3, and HSPB8, encoding three members of the small heat shock protein family. While around 30 different mutations in HSPB1 have been identified, the remaining three genes are altered in many fewer cases. Indeed, a mutation of HSPB3 has only been described in one case, whereas a few cases have been reported carrying mutations in DNAJB2 and HSPB8, most of them caused by a founder c.352+1G>A mutation in DNAJB2 and by mutations affecting the K141 residue in the HSPB8 chaperone. Hence, their rare occurrence makes it difficult to understand the pathological mechanisms driven by such mutations in this neuropathy. Chaperones can assemble into multi-chaperone complexes that form an integrated chaperone network within the cell. Such complexes fulfill relevant roles in a variety of processes, such as the correct folding of newly synthesized proteins, in which chaperones escort them to precise cellular locations, and as a response to protein misfolding, which includes the degradation of proteins that fail to refold properly. Despite this range of functions, mutations in some of these chaperones lead to diseases with a similar clinical profile, suggesting common pathways. This review provides an overview of the genetics of those dHMNs that share a common disease mechanism and that are caused by mutations in four genes encoding chaperones: DNAJB2, HSPB1, HSPB3, and HSPB8. PMID:28018906
Applegate, Vernon C.
An inclined-screen trap was installed on the Carp River, Emmett County, Michigan, in the spring of 1948 and has been in almost continuous operation since that time. The major goal of this project--a precise determination of the length of the larval life of sea lamprey--was not attained because of the contamination of the stream above the dam with spawning lampreys. The lampreys and other fishes collected in the trap did, however, provide extensive and valuable biological information. The present report documents much of the information, largely in tabular form, accumulated over the operating seasons, 1948-49 through 1957-58; the amount of detail has been varied according to the importance of the topic under consideration or the amount required to bring out a particular point.
two (1%) were given at home by the children's grandmothers. Since PISN is a ... neuropathy, especially in children, manifests by paresis in the distribution .... Injection safety: A global challenge. ... The Internet Journal of Third World. Medicine 3 ...
Dyrberg, Torben Bech; Benn, Jette; Christiansen, J S
To investigate the prevalence of diabetic autonomic neuropathy, five simple bedside tests, beat-to-beat variation during quiet respiration, beat-to-beat variation during forced respiration, heart rate and blood pressure response to standing, heart rate response to exercise, and heart rate response....... The prevalence of diabetic autonomic neuropathy in the whole diabetic population indicated by abnormal response in beat-to-beat variation during forced respiration was 27%. Diabetic autonimic neuropathy increased in frequency with duration of disease. Patients with nephropathy or proliferative retinopathy had...... a significantly higher prevalence of diabetic autonomic neuropathy as indicated by abnormal beat-to-beat variation during forced respirations (p less than 0.01) than patients without these complications....
Lee, Won Hyong; Chang, Hae Soon; Han, Man Chung; Lee, Suck Hyun; Lee, Duk Yong [Seoul National University College of Medicine, Seoul (Korea, Republic of)
Congenital sensory neuropathy with anhidrosis is rare disease and may be confused with other cause of pain insensitivity or indifference. Other cause of pain insensitivity include congenital indifference to pain, congenital sensory neuropathy, hereditary sensory radicular neuropathy, nonprogressive sensory radicular neuropathy, syringomyelia, and hysterical analgesia. It is hereditary disease which is transmitted with autosomal recessive trait. The patient is 8 years old Korean male with complaint of swelling and local heat on right knee joint. Generalized analgesia is noted on physical examination. The skin is dry and coarse with no evidence of sweating. Delayed motor development was noted on early children. Mental development is retarded. On past history, patient showed unpredictable rises of temperature, though the general condition remained good. Multiple painless fracture on right humerus and right metatasal bone was occurred. Rt.knee radiograms show marked swelling of soft tissue and periosteal calcification on distal femru,which are resemble with neurotrophic joint.
Wilmshurst, Jo M; Ouvrier, Robert
This review focuses on the "pure" hereditary peripheral neuropathies where peripheral nerve disease is the main manifestation and does not address neurodegenerative disorders associated with but not dominated by peripheral neuropathy. Aetiologies of childhood-onset peripheral neuropathies differ from those of adult-onset, with more inherited conditions, especially autosomal recessive. Charcot-Marie-Tooth disease is the commonest neuromuscular disorder. The genetic labels of CMT (Charcot-Marie-Tooth) disease types 1-4 are the preferred sub-type terms. Clinical presentations and molecular genetic heterogeneity of hereditary peripheral neuropathies are diverse. For most patients worldwide, diagnostic studies are limited to clinical assessment. Such markers which could be used to identify specific sub-types include presentation in early childhood, scoliosis, marked sensory involvement, respiratory compromise, upper limb involvement, visual or hearing impairment, pyramidal signs and mental retardation. These key markers may assist targeted genetic testing and aid in diagnosing children where DNA testing is not possible.
Full Text Available Out-of-wedlock childbearing is more common in the U.S. than in other countries and becoming more so. A growing share of such non-marital births identify the father, which can create a legal entitlement to child support. Relatively little is known about individual determinants of the decision to establish paternity, in part because of data limitations. In this paper, we evaluate all birth records in Michigan from 1993 to 2006, which have been merged to the paternity registry. In 2006, 30,231 Michigan children, almost one quarter of all Michigan births, were born to unmarried mothers and had paternity acknowledged. We find that births with paternity acknowledged have worse outcomes along various health and socio-economic dimensions relative to births to married parents, but better outcomes relative to births to unmarried parents without paternity acknowledgement. Furthermore, unmarried men who father sons are significantly more likely to acknowledge paternity than fathers of daughters.
Reid, M.W.; Weaver, E.M. (Barakat and Chamberlin, Inc., Oakland, CA (United States))
This is the final report of Phase I of the Michigan Regulatory Incentives Study for Electric Utilities, a three-phase review of Michigan's regulatory system and its effects on resource selection by electric utilities. The goal of Phase I is to identify and analyze financial incentive mechanisms that encourage selection of resources in accord with the principles of integrated resource planning (IRP) or least-cost planning (LCP). Subsequent study phases will involve further analysis of options and possibly a collaborative formal effort to propose regulatory changes. The Phase I analysis proceeded in three steps: (1) identification and review of existing regulatory practices that affect utilities; selection of resources, particularly DSM; (2) preliminary analysis of ten financial mechanisms, and selection of three for further study; (3) detailed analysis of the three mechanisms, including consideration of how they could be implemented in Michigan and financial modeling of their likely impacts on utilities and ratepayers.
Brewer, Jamie R; Morrison, Gladys; Dolan, M Eileen; Gini F Fleming
As there are increasing numbers of cancer survivors, more attention is being paid to the long term unwanted effects patients may experience as a result of their treatment and the impact these side effects can have on their quality of life. Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common long-term toxicities from chemotherapy. In this review we will briefly review the clinical presentation, evaluation and management of chemotherapy-induced peripheral neuropathy, wit...
Tenenbein, M; deGroot, W.; Rajani, K R
Two adolescent native Canadians who presented with peripheral neuropathy secondary to the abuse of volatile hydrocarbons are described. They were initially thought to have been sniffing leaded gasoline fumes, but public health investigation revealed that they had been sniffing naphtha fumes. Naphtha contains a significant amount of n-hexane, a known inducer of neuropathy. Nerve conduction studies and nerve biopsy confirmed the diagnosis of naphtha abuse. These cases emphasize the need to spec...
Tenenbein, M; deGroot, W; Rajani, K R
Two adolescent native Canadians who presented with peripheral neuropathy secondary to the abuse of volatile hydrocarbons are described. They were initially thought to have been sniffing leaded gasoline fumes, but public health investigation revealed that they had been sniffing naphtha fumes. Naphtha contains a significant amount of n-hexane, a known inducer of neuropathy. Nerve conduction studies and nerve biopsy confirmed the diagnosis of naphtha abuse. These cases emphasize the need to specifically identify the formulation of hydrocarbons being abused.
Russell, James W.; Berent-Spillson, Alison; Vincent, Andrea M.; Freimann, Catherine L.; Sullivan, Kelli A.; Feldman, Eva L.
Clinical studies suggest that impaired glucose tolerance (IGT) is associated with the development of neuropathy. The aim of the current study was to determine if neuropathy developed in the female Zucker Diabetic Fatty (ZDF) rat, an animal model of IGT and type 2 diabetes. The ZDF rat develops impaired glucose tolerance (IGT) when fed a control diet, and frank diabetes when fed a high fat diet. Following 10 weeks of hyperglycemia, sensory nerve action potentials (SNAP) and compound motor acti...
Tramontozzi, Louis A; Russell, James A
We report a patient with orthostatic intolerance and syncope as a major clinical manifestation of an acquired multifocal neuropathy with the clinical, electrodiagnostic, and cerebrospinal fluid features of multifocal acquired demyelinating sensory and motor neuropathy or the Lewis-Sumner syndrome. Immunomodulatory therapy led to clinical remission of both somatic and autonomic signs and symptoms. We are unaware of a previous description of symptomatic dysautonomia in this disorder.
Kannan, Anusha; Srinivasan, Sivasubramanian [Khoo Teck Puat Hospital, Singapore (Singapore)
We read with great interest, the case report on ischemic optic neuropathy (1). We would like to add a few points concerning the blood supply of the optic nerve and the correlation with the development of post-operative ischemic neuropathy. Actually, the perioperative or post-operative vision loss (postoperative ischemic neuropathy) is most likely due to ischemic optic neuropathy. Ischemic optic neuropathy (2) is classified as an anterior ischemic optic neuropathy (AION) and posterior ischemic optic neuropathy (PION). This classification is based on the fact that blood supply (2) to the anterior segment of the optic nerve (part of the optic nerve in the scleral canal and the optic disc) is supplied by short posterior ciliary vessels or anastamotic ring branches around the optic nerve. The posterior part of the optic canal is relatively less perfused, and is supplied by ophthalmic artery and central fibres are perfused by a central retinal artery. So, in the post-operative period, the posterior part of the optic nerve is more vulnerable for ischemia, especially, after major surgeries (3), one of the theories being hypotension or anaemia (2) and resultant decreased perfusion. The onset of PION is slower than the anterior ischemic optic neuropathy. AION on the other hand, is usually spontaneous (idiopathic) or due to arteritis, and is usually sudden in its onset. The reported case is most likely a case of PION. The role of imaging, especially the diffusion weighted magnetic resonance imaging, is very important because the ophthalmoscopic findings in early stages of PION is normal, and it may delay the diagnosis. On the other hand, edema of the disc is usually seen in the early stages of AION.
Full Text Available Leber's hereditary optic neuropathy characterized by loss of central vision is often seen in men and a maternally inherited disease. Here, admitted to our clinic with complaints of unilateral visual loss was diagnosed as Leber's hereditary optic neuropathy which was confirmed by the presence of a mutation at 3460G>A position. [Cukurova Med J 2012; 37(2.000: 121-124
Assessment of nutritional status of vitamin B components by plasma or blood levels indicated riboflavin deficiency and possibly thiamine deficiency in Nigerian patients who suffered from tropical ataxic neuropathy and neurologically normal Nigerians who subsisted on predominant cassava diet. Serum levels of folate, niacin, pyridoxine and panthothenic acid were normal. Vitamin deficiencies probably are minor factors, if any, in the pathogenesis of tropical ataxic neuropathy in Nigerians.
Mycobacterium kansasii was isolated from an area of cavitating pneumonia in a man with rheumatoid arthritis. Standard antituberculosis treatment, including isoniazid 300 mg daily, had to be stopped because of peripheral neuropathy. The patient, a slow acetylator, subjectively deteriorated despite withdrawal of isoniazid and treatment with pyridoxine 150 mg daily. Improvement occurred only after the pyridoxine had also been withdrawn. Pyridoxine may cause peripheral neuropathy and this case il...
Full Text Available The hereditary sensory and autonomic neuropathies are a rare group of disorders characterized by progressive loss of function that predominantly affects the peripheral sensory nerves. Autonomic dysfunction is present to a variable degree and can have several implications for anaesthesia. We report the case of a patient with Hereditary sensory and autonomic neuropathy who was posted for a below knee amputation and discuss the anaesthesia management.
Pierce, Aaron [Univ. of Michigan, Ann Arbor, MI (United States)
This award provided partial support for the Michigan Center for Theoretical Physics to host the 5-day workshop "Emergent themes in String Theory" this winter, March 15 - 19, 2016. on the University of Michigan campus. In addition, this award provided limited support for the Young High Energy Theorist (YHET) visitor program at the University of Michigan.
... Quality Control Regions § 81.67 Lake Michigan Intrastate Air Quality Control Region. The Menominee-Escanaba (Michigan)-Marinette (Wisconsin) Interstate Air Quality Control Region has been renamed the Lake Michigan Intrastate Air Quality Control Region (Wisconsin) and revised to consist of the territorial...
...; ] DEPARTMENT OF AGRICULTURE Agricultural Marketing Service 7 CFR Part 930 Tart Cherries Grown in Michigan, New... tart cherries grown in Michigan, New York, Pennsylvania, Oregon, Utah, Washington, and Wisconsin. These... handling of tart cherries grown in Michigan, New York, Pennsylvania, Oregon, Utah, Washington,...
Zheng, H; Xiao, W H; Bennett, G J
Many of the most effective anti-cancer drugs induce a dose-limiting peripheral neuropathy that compromises therapy. Evidence from animal models of chemotherapy-induced painful peripheral neuropathy produced by the taxane agent, paclitaxel, and the platinum-complex agent, oxaliplatin, indicate that they produce neuropathy via a common mechanism-a toxic effect on the mitochondria in primary afferent sensory neurons. Bortezomib is from the proteasome-inhibitor class of chemotherapeutics. It also produces a dose-limiting peripheral neuropathy, but its effects on neuronal mitochondria are unknown. To investigate this, we developed a model of bortezomib-induced painful peripheral neuropathy in the rat and assessed mitochondrial function (respiration and ATP production) in sciatic nerve samples harvested at two time points: day 7, which is three days after treatment and before pain appears, and day 35, which is one month post-treatment and the time of peak pain severity. We found significant deficits in Complex I-mediated and Complex II-mediated respiration, and in ATP production at both time points. Prophylactic treatment with acetyl-L-carnitine, which has previously been shown to prevent paclitaxel- and oxaliplatin-induced mitochondrial dysfunction and pain, completely blocked bortezomib's effects on mitochondria and pain. These results suggest that mitotoxicity may be the core pathology for all chemotherapy-induced peripheral neuropathy and that drugs that protect mitochondrial function may be useful chemotherapy adjuncts.
Rinaldi, Simon; Bennett, David L H
This review summarizes the major recent developments in understanding of pathogenic mechanisms in inflammatory and paraproteinaemic neuropathies. In the inflammatory neuropathies, there has been a particular focus on antibody-mediated disease affecting the nodal/paranodal regions. Disruption of electrical integrity at these sites on the axonal membrane can cause conduction block without other electrophysiological features of demyelination, which has led to calls for a revision in the classification of axonal versus demyelinating neuropathies to include the new category of 'nodo-paranodopathies'. There has likewise been an expansion in knowledge regarding the diverse disease mechanisms of the paraproteinaemic neuropathies. These also include disease mediated by antibodies binding to peripheral nerve antigens, but additionally encompass immune complex deposition, cellular infiltration, and cytokine production. An increasing range of laboratory tests for antibodies, growth factors, and cytokines are proposed as useful in the management of inflammatory and paraproteinaemic neuropathies. Furthermore, the traditional electrodiagnostic classification into axonal and demyelinating neuropathy may not always accurately reflect the underlying disease process. Understanding how these paraclinical tests aid in identifying the underlying disease has relevance to the practising clinician both in terms of diagnosis and for the selection of rational treatments.
Biousse, Valérie; Newman, Nancy J
Disorders of the optic nerves (optic neuropathies) are some of the most common causes of visual loss, and can present in isolation or with associated neurological or systemic symptoms and signs. Several optic neuropathies-especially inflammatory optic neuropathies-are associated with neurological disorders and thus are often diagnosed and treated by neurologists. The mechanisms underlying optic neuropathies are diverse and typically manifest with decreased visual acuity, altered colour vision, and abnormal visual field in the affected eye. Diagnosis is made on the basis of clinical history and clinical examination, of which several aspects are particularly important, including the mode of onset of visual loss, the presence of pain with eye movements, the visual acuity, and the retention of colour vision. Advances in optic nerve imaging-particularly retinal digital photography, optical coherence tomography, and MRI techniques-have revolutionised the diagnosis and follow-up of patients with an optic neuropathy. Furthermore, improvement and generalisation of some ancillary tests, such as diagnostic antibodies for neuromyelitis optica, allows better phenotyping of the heterogeneous inflammatory optic neuropathies. Copyright © 2016 Elsevier Ltd. All rights reserved.
Kumar, Anil; Mittal, Ruchika
Different aspects involved in pathophysiology of diabetic neuropathy are related to inflammatory and apoptotic pathways. This article summarizes evidence that Nrf2 acts as a bridging link in various inflammatory and apoptotic pathways impacting progression of diabetic neuropathy. Nrf2 is involved in expression of various antioxidant proteins (such as detoxifying enzymes) via antioxidant response element (ARE) binding site. Under normal conditions, Nrf2 is inactive and remains in the cytosol. Hyperglycemia is a strong stimulus for oxidative stress and inflammation that downregulates the activity of Nrf2 through various neuroinflammatory pathways. Acute hyperglycemia increases the expression of Nrf2, but persistent hyperglycemia decreases its expression. This downregulation of Nrf2 causes various microvascular changes, which result in diabetic neuropathy. The key contribution of Nrf2 in progression of diabetic neuropathy has been summarized in the article. Despite involvement of Nrf2 in progression of diabetic neuropathy, targeting Nrf2 activators as a therapeutic potential will provide important new insights into the ways that influence treatment of diabetic neuropathy.
Marshall, Andrew G; Lee-Kubli, Corinne; Azmi, Shazli; Zhang, Michael; Ferdousi, Maryam; Mixcoatl-Zecuatl, Teresa; Petropoulos, Ioannis N; Ponirakis, Georgios; Fineman, Mark S; Fadavi, Hassan; Frizzi, Katie; Tavakoli, Mitra; Jeziorska, Maria; Jolivalt, Corinne G; Boulton, Andrew J M; Efron, Nathan; Calcutt, Nigel A; Malik, Rayaz A
Impaired rate dependent depression (RDD) of the Hoffman-reflex is associated with reduced dorsal spinal cord potassium chloride co-transporter expression and impaired spinal GABAA receptor function, indicative of spinal inhibitory dysfunction. We have investigated the pathogenesis of impaired RDD in diabetic rodents exhibiting features of painful neuropathy and the translational potential of this marker of spinal inhibitory dysfunction in human painful diabetic neuropathy. Impaired RDD and allodynia were present in type 1 and type 2 diabetic rats but not in rats with type 1 diabetes receiving insulin supplementation that did not restore normoglycemia. Impaired RDD in diabetic rats was rapidly normalized by spinal delivery of duloxetine acting via 5HT2A receptors and temporally coincident with the alleviation of allodynia. Deficits in RDD and corneal nerve density were demonstrated in patients with painful diabetic neuropathy when compared to healthy control subjects and patients with painless diabetic neuropathy. Spinal inhibitory dysfunction and peripheral small fibre pathology may contribute to the clinical phenotype in painful diabetic neuropathy. Deficits in RDD may help to identify patients with spinally mediated painful diabetic neuropathy who may respond optimally to therapies such as duloxetine.
Rao, Deepa B; Jortner, Bernard S; Sills, Robert C
Despite the progress in our understanding of pathogeneses and the identification of etiologies of peripheral neuropathy, idiopathic neuropathy remains common. Typically, attention to peripheral neuropathies resulting from exposure to environmental agents is limited relative to more commonly diagnosed causes of peripheral neuropathy (diabetes and chemotherapeutic agents). Given that there are more than 80,000 chemicals in commerce registered with the Environmental Protection Agency and that at least 1000 chemicals are known to have neurotoxic potential, very few chemicals have been established to affect the peripheral nervous system (mainly after occupational exposures). A wide spectrum of exposures, including pesticides, metals, solvents, nutritional sources, and pharmaceutical agents, has been related, both historically and recently, to environmental toxicant-induced peripheral neuropathy. A review of the literature shows that the toxicity and pathogeneses of chemicals adversely affecting the peripheral nervous system have been studied using animal models. This article includes an overview of five prototypical environmental agents known to cause peripheral neuropathy--namely, organophosphates, carbon disulfide, pyridoxine (Vitamin B6), acrylamide, and hexacarbons (mainly n-hexane, 2,5-hexanedione, methyl n-butyl ketone). Also included is a brief introduction to the structural components of the peripheral nervous system and pointers on common methodologies for histopathologic evaluation of the peripheral nerves.
Heung Yong Jin
Full Text Available Diabetic neuropathy is one of the major complications of diabetes, and it increases morbidity and mortality in patients with both type 1 diabetes mellitus (T1DM and type 2 diabetes mellitus (T2DM. Because the autonomic nervous system, for example, parasympathetic axons, has a diffuse and wide distribution, we do not know the morphological changes that occur in autonomic neural control and their exact mechanisms in diabetic patients with diabetic autonomic neuropathy (DAN. Although the prevalence of sympathetic and parasympathetic neuropathy is similar in T1DM versus T2DM patients, sympathetic nerve function correlates with parasympathetic neuropathy only in T1DM patients. The explanation for these discrepancies might be that parasympathetic nerve function was more severely affected among T2DM patients. As parasympathetic nerve damage seems to be more advanced than sympathetic nerve damage, it might be that parasympathetic neuropathy precedes sympathetic neuropathy in T2DM, which was Ewing's concept. This could be explained by the intrinsic morphologic difference. Therefore, the morphological changes in the sympathetic and parasympathetic nerves of involved organs in T1DM and T2DM patients who have DAN should be evaluated. In this review, evaluation methods for morphological changes in the epidermal nerves of skin, and the intrinsic nerves of the stomach will be discussed.
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Sederholm, Benson H
Current treatment approaches for the management of chronic immune-mediated peripheral neuropathies are reviewed, including chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN), and the Lewis-Sumner syndrome (LSS). A summary of existing evidence for commonly used treatment modalities, such as corticosteroids, intravenous immune globulin (IVIG), and plasma exchange is provided. Evidence for the use of additional immunosuppressant and immunomodulatory agents is also reviewed.
Black, Christine; Harris, Bethany; Mahraj, Katy; Schnitzer, Anna Ercoli; Rosenzweig, Merle
Librarians have traditionally facilitated research development resulting in grants through performing biomedical literature searches for researchers. The librarians at the Taubman Health Sciences Library of the University of Michigan have taken additional steps forward by instituting a proactive approach to assisting investigators. To accomplish this, the librarians have taken part in a collaborative effort with the University of Michigan Medical School Office of Research. Through this partnership, both units have created and adopted various techniques intended to facilitate the submission of grants, thus allowing researchers more time to conduct their primary activities.
Knoerl, Robert; Dudley, William N; Smith, Gloria; Bridges, Celia; Kanzawa-Lee, Grace; Lavoie Smith, Ellen M
Because numerous barriers hinder the assessment and management of chemotherapy-induced peripheral neuropathy in clinical practice, the Carevive Care Planning System, a novel Web-based platform, was developed to address these barriers. It provides patients an opportunity to report their symptoms before their clinic visit and generates customizable care plans composed of evidence-based management strategies. The purpose of this study was to evaluate patient and provider perspectives of feasibility, usability, acceptability, and satisfaction with the Carevive platform. We used a single-arm, pretest/posttest, prospective design and recruited 25 women with breast cancer who were receiving neurotoxic chemotherapy and six advanced practice providers from an academic hospital. At three consecutive clinical visits, patients reported their neuropathy symptoms on a tablet via the Carevive system. The Diffusion of Innovations Theory served as an overarching evaluation framework. The Carevive platform was feasible to use. However, patients had higher ratings of usability, acceptability, and satisfaction with the platform than did the providers, who disliked the amount of time required to use the platform and had difficulty logging into Carevive. If issues regarding provider dissatisfaction can be addressed, the Carevive platform may aid in the screening of neuropathy symptoms and facilitate the use of evidence-based management strategies.
Full Text Available Objectives: To determine the prevalence and factor related with median neuropathy at wrist (MNW in systemic sclerosis patients. Study Design: Cross-sectional study. Setting: Srinagarind Hospital, Khon Kaen, Thailand. Participants: Systemic sclerosis patients who attended the Scleroderma Clinic, Srinagarind Hospital. Materials and Methods: Seventyfive systemic sclerosis patients were prospectively evaluated by questionnaire, physical examination, and electrodiagnostic study. The questionnaire consisted of the symptoms, duration, and type of systemic sclerosis. The physical examination revealed skin score of systemic sclerosis, pinprick sensation of median nerve distribution of both hands, and weakness of both abductor pollicis brevis muscles. The provocative test which were Tinel′s sign and Phalen′s maneuver were also examined. Moreover, electrodiagnostic study of the bilateral median and ulnar nerves was conducted. Results: The prevalence of MNW in systemic sclerosis patients was 44% - percentage of mild, moderate, and severe were 28%, 9.3%, and 6.7%, respectively. The prevalence of asymptomatic MNW was 88%. There were no association between the presence of MNW and related factors of systemic sclerosis. Conclusions: MNW is one of the most common entrapment neuropathies in systemic sclerosis patients. Systemic sclerosis patients should be screened for early signs of MNW.
These are two false-color composites of Raco, Michigan, located at the eastern end of Michigan's upper peninsula, west of Sault Ste. Marie and south of Whitefish Bay on Lake Superior. The two images (centered at 46.39 degrees north latitude, 84.88 degrees west longitude) show significant seasonal changes in the mid-latitude region of mixed deciduous and coniferous forests. The images were acquired by the Spaceborne Imaging Radar-C and X-band Synthetic Aperture Radar (SIR-C/X-SAR) aboard the shuttle Endeavour on the sixth orbit of each mission. In these images, red is L-band (23 cm) with horizontal/vertical polarization; green is C-band (6 cm) with horizontal/vertical polarization; blue is C-band with horizontal/horizontal polarization. The region shown is largely forested and includes a large portion of Hiawatha National Forest, as well as an agricultural region near the bottom of each image. In early April, the area was snow-covered with up to 50 centimeters (19.5 inches) of snow in forest clearings and agricultural fields. Buds had not yet broken on deciduous trees, but the trees were not frozen and sap was generally flowing. Lake Superior, in the upper right, and the small inland lakes were frozen and snow-covered on April 9, 1994. By the end of September, deciduous trees were just beginning to change color after a relatively wet period. Leaf loss was estimated at about 30 percent, depending on the species, and the soil was moist to wet after a heavy rainfall on September 28, 1994. Most agricultural fields were covered with grasses of up to 60 centimeters (23 inches) in height. In the two images the colors are related to the types of land cover (i.e. vegetation type) and the brightness is related to the amount of plant material and its relative moisture content. Significant seasonal changes between early spring and early fall are illustrated by this pair of images. For the agricultural region near the bottom of the images, the change from snow-cover to moist
Full Text Available Professional management of paediatric diabetology, according to consensus guidelines, involves the screening of micro-vascular complications at puberty. The subclinical form of peripheral neural dysfunction in diabetic teenagers is reported with a frequency of 50-88%, by different authors. The purpose of this study was to evaluate the frequency of subclinical distal neuropathy (DSMN in type 1 diabetic pediatric patients during the second decade of life, and its relationship with metabolic control. The Endocrinology Department and the Neurology-Physiology Laboratory of the Pediatric Clinic in Belgrade carried out a longitudinal follow-up study (lasting 18 months, beginning in November 2000 on a selection of patients with poor metabolic control. During routine clinical treatment, patients were evaluated using the electrophysiological diagnostic method on peripheral neural dysfunction, a subclinical form of neuropathy. Metabolic control was manifested through HbA1c levels, measured every 3 months, using ion-exchange chromatography. Finally, here is the data collected from the clinical follow-up investigation of 60 children, aged 13-19 (median 1S.S±2.2, with duration of diabetes from 2-16 years (median b.3±3.b, and on the following therapies: 43 CT-conventional and 17 IIT-intensive, and insulin dose/day, median 1.02 (0.6-2.1 U/kg. Detected DSMN parameters at the beginning and at the end of the study were also noted. DSMN frequency was positive, at 64% for HbA1c of 9.44; DSMN dysfunction was reversed in 5% of the patients, for HbA1c of 10.17; the worst result was the progression of DSMN at 6.7% for HbA1c of 10.52; 6.7% had negative DSMN, with improved metabolic control, for HbA1c of 8.4; 15% of the examinations were unfinished (+/*. ANOVA statistical analysis showed a significant statistical relationship between metabolic control (HbA1c levels and DSMN neuropathy (sig. 0.043, p<0.05. There was no significant relationship between the reversion of
Abstract Background We hypothesized that a wide range of surgical procedures may be complicated by neuropathies, not just in close proximity but also remote from procedural sites. The aim of this study was to classify post-operative neuropathies and the procedures associated with them. Methods We retrospectively identified 66 patients diagnosed with post-procedure neuropathies between January 2005 and June 2008. We reviewed their referral cards and medical records for patient demographics, information on procedures, symptoms, as well as clinical and neurophysiological findings. Results Thirty patients (45.4%) had neuropathies remote from procedural sites and 36 patients (54.5%) had neuropathies in close proximity to procedural sites. Half of the remote neuropathies (15\\/30) developed following relatively short procedures. In 27% of cases (8\\/30) remote neuropathies were bilateral. Seven patients developed neuropathies remote from operative sites following hip arthroplasties (7\\/30: 23.3%), making hip arthroplasty the most common procedure associated with remote neuropathies. Sciatic neuropathies due to hip arthroplasty (12\\/36, 33.3%) accounted for the majority of neuropathies occurring in close proximity to operative sites. Five medial cutaneous nerve of forearm neuropathies occurred following arterio-venous fistula (AVF) formation. Conclusions An array of surgical procedures may be complicated by neuropathy. Almost half of post-procedure neuropathies occur remote from the site of procedure, emphasizing the need to try to prevent not just local, but also remote neuropathies. Mechanical factors and patient positioning should be considered in the prevention of post-operative neuropathies. There is a possible association between AVF formation and medial cutaneous nerve of forearm neuropathy, which requires further study for validation.
Background We hypothesized that a wide range of surgical procedures may be complicated by neuropathies, not just in close proximity but also remote from procedural sites. The aim of this study was to classify post-operative neuropathies and the procedures associated with them. Methods We retrospectively identified 66 patients diagnosed with post-procedure neuropathies between January 2005 and June 2008. We reviewed their referral cards and medical records for patient demographics, information on procedures, symptoms, as well as clinical and neurophysiological findings. Results Thirty patients (45.4%) had neuropathies remote from procedural sites and 36 patients (54.5%) had neuropathies in close proximity to procedural sites. Half of the remote neuropathies (15/30) developed following relatively short procedures. In 27% of cases (8/30) remote neuropathies were bilateral. Seven patients developed neuropathies remote from operative sites following hip arthroplasties (7/30: 23.3%), making hip arthroplasty the most common procedure associated with remote neuropathies. Sciatic neuropathies due to hip arthroplasty (12/36, 33.3%) accounted for the majority of neuropathies occurring in close proximity to operative sites. Five medial cutaneous nerve of forearm neuropathies occurred following arterio-venous fistula (AVF) formation. Conclusions An array of surgical procedures may be complicated by neuropathy. Almost half of post-procedure neuropathies occur remote from the site of procedure, emphasizing the need to try to prevent not just local, but also remote neuropathies. Mechanical factors and patient positioning should be considered in the prevention of post-operative neuropathies. There is a possible association between AVF formation and medial cutaneous nerve of forearm neuropathy, which requires further study for validation. PMID:20398427
Full Text Available Abstract Background We hypothesized that a wide range of surgical procedures may be complicated by neuropathies, not just in close proximity but also remote from procedural sites. The aim of this study was to classify post-operative neuropathies and the procedures associated with them. Methods We retrospectively identified 66 patients diagnosed with post-procedure neuropathies between January 2005 and June 2008. We reviewed their referral cards and medical records for patient demographics, information on procedures, symptoms, as well as clinical and neurophysiological findings. Results Thirty patients (45.4% had neuropathies remote from procedural sites and 36 patients (54.5% had neuropathies in close proximity to procedural sites. Half of the remote neuropathies (15/30 developed following relatively short procedures. In 27% of cases (8/30 remote neuropathies were bilateral. Seven patients developed neuropathies remote from operative sites following hip arthroplasties (7/30: 23.3%, making hip arthroplasty the most common procedure associated with remote neuropathies. Sciatic neuropathies due to hip arthroplasty (12/36, 33.3% accounted for the majority of neuropathies occurring in close proximity to operative sites. Five medial cutaneous nerve of forearm neuropathies occurred following arterio-venous fistula (AVF formation. Conclusions An array of surgical procedures may be complicated by neuropathy. Almost half of post-procedure neuropathies occur remote from the site of procedure, emphasizing the need to try to prevent not just local, but also remote neuropathies. Mechanical factors and patient positioning should be considered in the prevention of post-operative neuropathies. There is a possible association between AVF formation and medial cutaneous nerve of forearm neuropathy, which requires further study for validation.
Joel M. Phillips M.S., OTRL
Full Text Available The purpose of this study was to create a norm reference of current grip and pinch strength norms for working-age Michigan adults. This normative study included a convenience sample of 179 volunteers who were employees at car plants in South East Michigan or hospital sites in West Michigan. Participants’ ages ranged from between 20 and 62 years of age with a mean age of 49.15 years. There were 78 females (44% and 101 males (56%. Subjects were classified by gender and in the age categories of ages 20 to 49 years and ages 50-62 years. Grip and pinch strength norms were collected following the American Society of Hand Therapy protocol. The norms from these working adults were calculated with descriptive statistics for males and females in two age classifications: ages 20 to 49 and ages 50 to 62 years. Standard Errors (SE are better than the 1985 norms for both males and females ages 20 to 49 years. SEs are higher than the ages 20 to 49 years’ norms for the ages 50 to 62 years age categories in both males and females. These norms offer a point of comparison for clinicians to use for clients in Michigan who are ages 20 to 62 years and who have a goal to improve their grip strength. Clients’ grip and pinch strength could be compared to their age level or gender norms using the comparison for one standard deviation above, below, or at the means.
No area within the Iron River 1/sup 0/ x 2/sup 0/ Quadrangle, Michigan and Wisconsin, appears to be favorable for the existence of a minimum of 100 tons of U/sub 3/O/sub 8/ at a grade of 0.01 percent or better.
The Lake Michigan (LM) Mass Balance Study was conducted to measure and model polychlorinated biphenyls (PCBs) and other anthropogenic substances to gain a better understanding of the transport, fate, and effects of these substances within the system and to aid managers in the env...
Saada, Najwan L.
This multiple case study examines how 4 social studies teachers in 2 private Islamic schools in Michigan understand the concept of citizenship education and the dilemmas they face in teaching for unity and diversity and in helping their students negotiate their civics identities within the American sociopolitical context. Data were collected…
This research paper describes the development of spatial statistical tools that are applied to investigate the spatial trends of sediment data sets for nutrients and carbon in Lake Michigan. All of the sediment data utilized in the present study was collected over a two year per...
Rasmussen, Lucinda A.
This paper presents the author's comments on the Michigan sex offender registration article "Family Experiences of Young Adult Sex Offender Registration" (Comartin, Kernsmith, & Miles, 2010). The article is an important piece of research that addresses a much neglected and almost invisible population in the annals of research: the families of…
Rasmussen, Lucinda A.
This paper presents the author's comments on the Michigan sex offender registration article "Family Experiences of Young Adult Sex Offender Registration" (Comartin, Kernsmith, & Miles, 2010). The article is an important piece of research that addresses a much neglected and almost invisible population in the annals of research: the…
MacDonald, R. A.; Longstaffe, F. J.; Crowe, A. S.
We present stable isotope records for porewater (oxygen, hydrogen) and biogenic carbonates (oxygen, carbon; ostracode and clam shells) in sediment cores from the Chippewa, Milwaukee and South Chippewa Basins of Lake Michigan. The oxygen and hydrogen isotope compositions of porewater from the South Chippewa Basin core showed very little variation with depth. At the maximum depth of 16.6m, δ18O values were within 2‰ and δD values were within 12‰ of modern Lake Michigan water (average δ18O = -5.9‰; average δD = -45‰); original porewater compositions have not been preserved. The oxygen isotope results for the biogenic carbonates, by comparison, provide a record of the isotopic composition of Lake Michigan over the last ~11,000 years, including significant incursions of very low-18O water, as first reported by Colman et al. (1990) and Forester et al. (1994). The low-18O waters originated from the retreating Laurentide ice sheet and may have been routed through Lakes Agassiz and Superior and discharged as large volumes over very short intervals of time. Periods characterized by much higher oxygen isotope compositions likely record the isotopic composition of regional precipitation over the catchment area. In summary, the large variations in the oxygen isotope composition of early Lake Michigan water arose from regional climate change and changing water sources during the times of ice-sheet retreat.
Blower, D; Campbell, K L; Green, P E
Accident rates of heavy truck-tractors are modelled using log-linear methods. The accident data used are a census of truck-tractor involvements in Michigan from May 1987 to April 1988. Travel data used to calculate the rates were produced by a survey of truck-tractors in Michigan covering the same time period. Both the accident and travel data were limited to Michigan-registered tractors operating in Michigan. Log-linear models of casualty and property-damage-only accident rates were developed using number of trailers, road type, area type, and time of day as predictor variables. Overall, differences between tractors with one and two trailers were not significant. Tractors with no trailers (bobtails) have significantly higher accident rates. Characteristics of the operating environment were found to have larger effects on the accident rate than tractor configuration (except for the bobtail). Rates varied by a factor of up to 6.8, depending on the road type. Casualty accident risk at night was 1.4 times the risk during the day. The risk of a casualty accident in rural areas was 1.6 times that of urban areas.
... COMMISSION 47 CFR Part 73 Radio Broadcasting Services; Evart and Ludington, Michigan AGENCY: Federal... filing procedures for comments, see 47 CFR 1.415 and 1.420. List of Subjects in 47 CFR Part 73 Radio, Radio broadcasting. Federal Communications Commission. Nazifa Sawez, Assistant Chief, Audio...
U.S. Geological Survey, Department of the Interior — Each line in the file âLake Michigan fish acoustic data from 2011 to 2016.csvâ represents the acoustic data and estimated fish density for a single depth layer...
The University of Michigan (U-M) has an award-winning history of sustainability initiatives, including research and student activism as well as campus facilities-related efforts. Environmental conservation programs on campus include alternative transportation, energy audits of and improvements to campus buildings, green purchasing, use of…
Victor, David A.
In January 2006, the College of Business at Eastern Michigan University (EMU) instituted a cross-disciplinary program in international business (IB). Business communication is a major component of the program. Moreover, the need for business communication in other languages contributed greatly to the cross-disciplinary nature of the program. This…
Black, Leah; Hyslop, Colleen
Working conditions in library technical services departments can be a problem for catalogers in need of a quiet work environment. Based on a successful program for indexers at the National Agriculture Library, a proposal for an experimental telecommuting program for original cataloging at the Michigan State University Libraries was developed and…
Black Issues in Higher Education, 1989
A University of Michigan policy barred harassment or discrimination based on race, ethnicity, religion, sex, sexual orientation, creed, national origin, ancestry, age, marital status, handicapped, or Vietnam-veteran status. It was declared unconstitutional because it violated First Amendment rights. University officials may rewrite policy or…
Ferrari, Luiz F; Levine, Jon D
A major dose-limiting side effect of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) chemotherapies, such as the nucleoside reverse transcriptase inhibitors (NRTIs), is a small-fiber painful peripheral neuropathy, mediated by its mitochondrial toxicity. Co-morbid conditions may also contribute to this dose-limiting effect of HIV/AIDS treatment. Alcohol abuse, which alone also produces painful neuropathy, is one of the most important co-morbid risk factors for peripheral neuropathy in patients with HIV/AIDS. Despite the prevalence of this problem and its serious impact on the quality of life and continued therapy in HIV/AIDS patients, the mechanisms by which alcohol abuse exacerbates highly active antiretroviral therapy (HAART)-induced neuropathic pain has not been demonstrated. In this study, performed in rats, we investigated the cellular mechanism by which consumed alcohol impacts antiretroviral-induced neuropathic pain. NRTI 2',3'-dideoxycytidine (ddC; 50 mg/kg) neuropathy was mitochondrial-dependent and PKCε-independent, and alcohol-induced painful neuropathy was PKCε-dependent and mitochondrial-independent. At low doses, ddC (5 mg/kg) and alcohol (6.5% ethanol diet for 1 week), which alone do not affect nociception, together produce profound mechanical hyperalgesia. This hyperalgesia is mitochondrial-dependent but PKCε-independent. These experiments, which provide the first model for studying the impact of co-morbidity in painful neuropathy, support the clinical impression that alcohol consumption enhances HIV/AIDS therapy neuropathy, and provide evidence for a role of mitochondrial mechanisms underlying this interaction.
Di Stefano, G; La Cesa, S; Leone, C; Pepe, A; Galosi, E; Fiorelli, M; Valeriani, M; Lacerenza, M; Pergolini, M; Biasiotta, A; Cruccu, G; Truini, A
Although the most widely agreed neurophysiological tool for investigating small fibre damage is laser evoked potential (LEP) recording, no study has documented its diagnostic accuracy. In this clinical, neurophysiological and skin biopsy study we collected age-corrected LEP normative ranges, verified the association of LEPs with pinprick sensory disturbances in the typical diabetic mixed-fibre polyneuropathy and assessed the sensitivity and specificity of LEPs in diabetic small-fibre neuropathy.From 288 LEP recordings from the face, hand and foot in 73 healthy subjects we collected age-corrected normative ranges for LEPs. We then selected 100 patients with mixed-fibre diabetic neuropathy and 25 patients with possible small-fibre diabetic neuropathy. In the 100 patients with mixed-fibre neuropathy we verified how LEP abnormalities were associated with clinically evident pinprick sensory disturbances. In the 25 patients with possible pure small-fibre neuropathy, using the skin biopsy for assessing the intraepidermal nerve fibre density, as a reference standard, we calculated LEP sensitivity and specificity.In healthy participants, age strongly influenced normative ranges for all LEP variables. By applying age-corrected normative ranges for LEPs, we found that LEPs were strongly associated with pinprick sensory disturbances. In relation to the skin biopsy findings, LEPs yielded 78% sensitivity and 81% specificity in the diagnosis of diabetic small-fibre neuropathy.Our study, providing age-corrected normative ranges for the main LEP data and their diagnostic accuracy, helps to make LEPs more reliable as a clinical diagnostic tool, and proposes this technique as a less invasive alternative to skin biopsy for diagnosing diabetic small-fibre neuropathy.
Lupo, Vincenzo; García-García, Francisco; Sancho, Paula; Tello, Cristina; García-Romero, Mar; Villarreal, Liliana; Alberti, Antonia; Sivera, Rafael; Dopazo, Joaquín; Pascual-Pascual, Samuel I; Márquez-Infante, Celedonio; Casasnovas, Carlos; Sevilla, Teresa; Espinós, Carmen
Charcot-Marie-Tooth disease is characterized by broad genetic heterogeneity with >50 known disease-associated genes. Mutations in some of these genes can cause a pure motor form of hereditary motor neuropathy, the genetics of which are poorly characterized. We designed a panel comprising 56 genes associated with Charcot-Marie-Tooth disease/hereditary motor neuropathy. We validated this diagnostic tool by first testing 11 patients with pathological mutations. A cohort of 33 affected subjects was selected for this study. The DNAJB2 c.352+1G>A mutation was detected in two cases; novel changes and/or variants with low frequency (A mutation was also detected in three additional families. On haplotype analysis, all of the patients from these five families shared the same haplotype; therefore, the DNAJB2 c.352+1G>A mutation may be a founder event. Our gene panel allowed us to perform a very rapid and cost-effective screening of genes involved in Charcot-Marie-Tooth disease/hereditary motor neuropathy. Our diagnostic strategy was robust in terms of both coverage and read depth for all of the genes and patient samples. These findings demonstrate the difficulty in achieving a definitive molecular diagnosis because of the complexity of interpreting new variants and the genetic heterogeneity that is associated with these neuropathies. Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.
Gul Mete Civelek
Full Text Available Neuropathic pain is defined as %u201Cpain occuring as a direct result of a disease or lesion directly affecting somato-sensorial system%u201D. Painful diabetic neuropathy (PDN is a serious complication impairing quality of life of patients. Researchs show that PDN affects approximately 16% of patients with diabetes. An important part of the PDN patients (39% remain without treatment. The diagnosis of neuropathic pain is a clinical diagnosis. Pain can be described by patients as burning, throbbing, numbness, tingling, anesthetic, pins and needles or blunt pain. Neuropathic pain is accompanied by sensory disorders such as dysesthesia, allodynia (pain heard by a stimulus not creating pain or hyperalgesia ( reduction of pain threshold for a painful stimulus. PDN develops in almost half of diabetic patients within the first ten years of diabetes. Over time, muscle loss, decreased deep tendon reflexes and trophic skin changes can be observed. Treatment guidelines agree that some agents such as pregabalin, gabapentin, tricyclic antidepressants should be preferred in the first line and have controversial proposals for some agents such as duloxetine. This shows the need for more research on the issue. It is important for all physicians dealing with pain, to recognize PDN and prefer evidence-based treatment approaches for patient benefit. In this review pharmacological treatment of PDN is discussed in light of current research and treatment guidelines.
Goldsmith, B J; Rosenthal, S A; Wara, W M; Larson, D A
Radiation-induced optic neuropathy (RON) is a rare and catastrophic complication of currently employed radiation therapy regimens for meningiomas that have been partially resected and sampled for biopsy. Between 1972 and 1989, 49 patients received postoperative irradiation for partially resected or biopsy sampled meningiomas, with the optic nerve within the treatment field. One patient experienced RON. The latency period for this case was 23 months. A review of the literature disclosed few cases of RON after treatment for meningioma; however, 42 cases of RON have been reported after radiation therapy for other lesions. The authors constructed two approaches to predict optic nerve radiation tolerance. The first is modeled on a previous proposal for a neural tissue nominal standard dose term and enabled accurate prediction of safe treatment regimens and risk of RON. This approach compared favorably with previously employed nominal standard dose terms. The second approach, based on the linear-quadratic model, proved unsuccessful due to its failure to achieve statistical significance.
Nakamura, Makoto; Mimura, Osamu; Wakakura, Masato; Inatani, Masaru; Nakazawa, Toru; Shiraga, Fumio
Designation criteria for Leber's hereditary optic neuropathy (LHON) have been established by a working group for retino-choroidal and optic atrophy funded by the Ministry of Health, Labor, and Welfare (MHLW) of Japan in collaboration with the Japanese Neuro-ophthalmology Society. The criteria are composed of three major symptoms and three ancillary test findings. According to the number and the combination of these symptoms and findings, subjects are classified into definite, probable, and possible LHON cases and asymptomatic carriers. The major symptoms include bilateral involvement with a time-lag, a papillomacular bundle atrophy, both characteristic optic disc findings at the acute phase. In the ancillary testings, mitochondrial DNA mutations specific for LHON are detailed with a table listing the mutation loci being attached. To enhance readers' understanding of description of the major symptoms and ancillary test findings, explanatory remarks on 11 parameters are supplemented. The establishment of the criteria facilitates epidemiological survey of LHON by MHLW and contributes to improvement of welfare for patients with LHON in Japan.
Full Text Available Diabetic neuropathy (DN is a widespread disabling disorder comprising peripheral nerves' damage. DN develops on a background of hyperglycemia and an entangled metabolic imbalance, mainly oxidative stress. The majority of related pathways like polyol, advanced glycation end products, poly-ADP-ribose polymerase, hexosamine, and protein kinase c all originated from initial oxidative stress. To date, no absolute cure for DN has been defined; although some drugs are conventionally used, much more can be found if all pathophysiological links with oxidative stress would be taken into account. In this paper, although current therapies for DN have been reviewed, we have mainly focused on the links between DN and oxidative stress and therapies on the horizon, such as inhibitors of protein kinase C, aldose reductase, and advanced glycation. With reference to oxidative stress and the related pathways, the following new drugs are under study such as taurine, acetyl-L-carnitine, alpha lipoic acid, protein kinase C inhibitor (ruboxistaurin, aldose reductase inhibitors (fidarestat, epalrestat, ranirestat, advanced glycation end product inhibitors (benfotiamine, aspirin, aminoguanidine, the hexosamine pathway inhibitor (benfotiamine, inhibitor of poly ADP-ribose polymerase (nicotinamide, and angiotensin-converting enzyme inhibitor (trandolapril. The development of modern drugs to treat DN is a real challenge and needs intensive long-term comparative trials.
Hema L Ramkumar
Full Text Available A 60-year-old woman with a history of chronic alcoholism and tobacco use presented with the complaint of a painless decrease in vision in both eyes. She lost vision first in the left eye then in the right eye. She admitted consuming at least one 16 ounce bottle of over the counter mouthwash daily and denied consumption of any other alcohols, methanol, or antifreeze. She stated that her vision had been continuing to deteriorate in both eyes. Her best-corrected visual acuity was 4/200 in each eye. Color vision was nil in each eye. Her pupils were sluggish bilaterally, and her optic discs were flat and hyperemic with peripapillary hemorrhages. Her visual fields revealed central scotomas bilaterally. The magnetic resonance imaging of the brain and lumbar puncture were within normal limits. Antinuclear antibody, human leukocyte antigen-B27 genotyping, and B12 were normal; serum thiamine was low. While continuing to ingest mouthwash, her vision decreased to count fingers at 2 feet, and maculopapillary bundle pallor developed. She was started on folate and thiamine supplementation. Once she discontinued mouthwash, her vision improved to 20/400 bilaterally, and her central scotomas improved. This case demonstrates an alcohol-induced toxic optic neuropathy from mouthwash ingestion with some visual recovery after discontinuation of the offending agent.
Selvaraj, Vinoth Kanna; Devanathan, Vasudevan
Visual impairment following head injury may be an enigma especially if the onset of symptoms were to be few days after the actual trauma and the bias arising out of the initial normal ophthalmological examination is not neutralised by unbiased repeated formal clinical evaluation aided with electrophysiology. We report and discuss here a 32-year-old lady with delayed onset of indirect traumatic visual loss with anaemia who failed to improve after blood transfusion but improved immediately following steroid therapy seven days after trauma. Though steroids have not been shown to have a significant contribution on outcomes following Traumatic optic neuropathy, this report rekindles its role in delayed progressive visual loss following head trauma and the need to re-analyse the role of steroids in patients with delayed progressive visual disturbance following head injury excluding those with acute onset symptoms in view of different pathologies in both these presentations. This paper also highlights potential mechanisms for the two major types of presentation. PMID:27134913
@@ Diabetic neuropathy (DN) is the most common metabolic neuropathy in clinics, not only in diabetes patients (>60%), but also in pre-diabetic (8%) and normal persons (5%)(1). Its pathogenesis has not been fully understood up to now.
Objective To observe the clinical effectiveness of alprostadil combined with pancreatic kininogenas in the treatment of gerontal diabetic peripheral neuropathy.Methods Totally 90 gerontal patients with diabetic peripheral neuropathy were randomly divided into three
Lynch, E.A.; Huffman, G.C.
A leaking underground storage tank was removed from the Michigan Department of Transportation maintenance garage area in Kalamazoo County., Mich., in 1985. The tank had been leaking unleaded gasoline. Although a remediation system was operational at the site for several years after the tank was removed, ground-water samples collected from monitoring wells in the area consistently showed high concentrations of benzene, toluene. ethylbenzene, and xylenes--indicators of the presence of gasoline. The U.S. Geological Survey did a study in cooperation with the Michigan Department of Transportation, to define the geology, hydrology, and occurrence of gasoline contamination in the maintenance garage area. The aquifer affected by gasoline contamination is an unconfined glaci'a.l sand and gravel aquifer. The average depth to water in the study area is about 74.7 feet. Water-level fluctuations are small; maximum fluctuation was slightly more than 1 foot during August 1993-August 1994. Hydraulic conductivities based on aquifer-test data collected for the study and estimated by use of the Cooper-Jacob method of solution ranged from 130 to 144 feet per day. Ground water is moving in an east-southeasterly direction at a rate of about I foot per day. Leakage from perforated pipes leading from the underground storage tanks to the pump station was identified as a second source of gasoline contamination to saturated and unsaturated zones. The existence of this previously unknown second source is part of the reason that previous remediation efforts were ineffective. Residual contaminants in the unsaturated zone are expected to continue to move to the water table with recharge, except in a small area covered by asphalt at the land surface. The gasoline plume from the perforated pipe source has merged with that from the leaking underground storage tank, and the combined plume in the saturated zone is estimated to cover an area of 30,000 square feet. The combined plume is in the upper 20
Fish communities were surveyed at 20 wadable stream sites during 1993-95 as part of the U.S. Geological Survey's (USGS) National Water- Quality Assessment (NAWQA) Program's assessment of the Western Lake Michigan Drainages. Part of the NAWQA design is to incorporate ecological data into an overall environmental assessment. Collection of fish-community data was part of this ecological assessment.
Fu Liong, Hiew; Santhi, Datuk Puvanarajah; Shanthi, Viswanathan; Mohd Hanip, Rafia
Background. Since 2008, we have observed an increasing number of Myanmarese refugees in Malaysia being admitted for acute/subacute onset peripheral neuropathy. Most of them had a preceding history of starvation. Methods. We retrospectively studied the clinical features of all Myanmarese patients admitted with peripheral neuropathy from September 2008 to January 2014. Results. A total of 24 patients from the Chin, Rohingya, and Rakhine ethnicities (mean age, 23.8 years; male, 96%) had symmetrical, ascending areflexic weakness with at least one additional presenting symptom of fever, lower limb swelling, vomiting, abdominal pain, or difficulty in breathing. Twenty (83.3%) had sensory symptoms. Ten (41.6%) had cranial nerve involvement. Nineteen patients had cerebrospinal fluid examinations but none with evidence of albuminocytological dissociation. Neurophysiological assessment revealed axonal polyneuropathy, predominantly a motor-sensory subtype. Folate and vitamin B12 deficiencies were detected in 31.5% of them. These findings suggested the presence of a polyneuropathy related to nutrition against a backdrop of other possible environmental factors such as infections, metabolic disorders, or exposure to unknown toxin. Supportive treatment with appropriate vitamins supplementation improved functional outcome in most patients. Conclusion. We report a spectrum of acquired reversible neurological manifestations among Myanmarese refugees likely to be multifactorial with micronutrient deficiencies playing an important role in the pathogenesis.
Zyss, Julie; Béhin, Anthony; Couvert, Philippe; Bouhour, Françoise; Sassolas, Agnès; Kolev, Ivan; Denys, Violaine; Vial, Christophe; Lacour, A; Carrié, Alain; Stojkovic, Tanya
Tangier disease (TD) (OMIM#205400) is a rare autosomal recessive disorder resulting from mutations in the ABCA1 gene, leading to decreased levels of plasma high-density lipoproteins (HDL). Peripheral neuropathy is a common finding in this disease, and may present as relapsing/remitting mono/polyneuropathies or as syringomyelia-like neuropathy. We retrospectively analyzed four patients, and report here their clinical, biological, electrophysiological, imaging, and genetic findings. Three patients had a typical pseudosyringomyelic neuropathy including facial diplegia, but asymmetrical onset was observed in one patient who had first been misdiagnosed with Lewis-Sumner syndrome. Electrophysiological pattern was heterogeneous, showing both signs of demyelination and axonal degeneration. Truncating mutations of the ABCA1 gene, including two previously undescribed mutations, were constantly found. Atypical symptom onset and demyelinating features on electrophysiological examination can be misleading in case of pseudosyringomyelic neuropathy. These reports illustrate two different neurological phenotypes in TD, namely the pseudosyringomyelic type and the Lewis-Sumner-like type, and advocate for a systematic assessment of lipid profile including HDL cholesterol in demyelinating neuropathies.