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Cryptogenic Polyneuropathy: Clinical, Environmental, And Genetic Studies
Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. (Polyneuropatigruppen, Neurofys, Linköping)
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Objectives: The purpose of this medical thesis was to describe the clinical and neurophysiological features and to evaluate the health related quality of life (HR-QoL) in patients with cryptogenic polyneuropathy. We also wanted to investigate different occupational, and leisure time exposures as determinants for cryptogenic polyneuropathy, and to analyze whether polymorphisms for the null alleles of Glutathione S-Transferase Mu-1 (GSTM1), and Theta-1 (GSTT1), and a low activity genetic variation of epoxide hydrolase (EPHX) affect the risk of developing polyneuropathy. These genes were chosen because their enzymes are important in the metabolism of toxic compounds.

Methods: The medical records of all patients aged 40–79 years with the diagnosis of cryptogenic polyneuropathy from 1993 to 2000 were analyzed, and data regarding clinical symptoms, laboratory findings, and neurophysiological findings at diagnosis were collected. 255 cases were found. When the medical records were reevaluated assessment to a protocol 168 patients remained as cryptogenic. Two validated instruments (SF-36 and EQ-5D) for measuring HR-QoL were sent to patients, and a reference group from the general population. Additional clinical information, and data on occupational, and leisure time exposure was obtained from postal questionnaires. Crude odds ratios (COR), and logistic regression odds ratios (LOR) were calculated for exposures with five or more exposed cases and referents taken together. We also tested for genetic polymorphisms of GSTM1 and GSTT1, and epoxide hydrolase exon three, EPHX*3.

Results: 68% of the patients were men. The mean age at first symptom was 61 years and at diagnosis 64 years. Distal numbness was the most common symptom, but pain, pedal paresthesias, and impairment of balance were also common. The most common clinical findings were decreased or lost proprioception or sense of vibration (80%), and loss of ankle jerks (78%). Neurography showed mixed sensorimotor polyneuropathy of axonal or mixed axonal and demyelinating type. QOL was significantly affected concerning motor functions, with 42% of the patients reporting problems to walk, 3% having problems with daily activities, and 85% were suffering from pain. Mental health was preserved. Mobility was declining with increasing age, but was not affected by disease duration. Increased risks were found in men for occupational exposure to sulphur dioxide, xylene, methyl ethyl ketone, and herbicides and in women for occupational exposure to lead, nitrous oxide, and insecticides. Interaction between occupational and leisure time exposure were seen for several exposures. No significant correlation was found between GSTM1, GSTT1, and EPHX1 polymorphisms in patients with cryptogenic polyneuropathy compared with controls. A tendency, however, was seen for the GSTT1 null phenotype, which was enhanced among smokers compared to controls (OR 3.7).

Conclusions: Cryptogenic polyneuropathy is a slowly progressive sensorimotor nerve lesion of mainly axonal type. Patients with cryptogenic polyneuropathy have a lower QOL compared to the general population, although mental health scores did not differ between the groups. Our results show that known determinants could be confirmed, but also some new appeared i.e. sulphur dioxide, hydrogen sulphide, fungicides, and vibrations in the feet. Moreover our results point to a synergistic effect of various exposures. Our hypothesis is that the GSTT1 null polymorphism may be related to an impaired metabolism of toxic substances and reactive oxygen that could lead to nerve damage in the peripheral nervous system. Our results are indicating that components in cigarette smoke might increase the risk of axonal neuropathy in genetically predisposed patients.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press , 2011. , 12´2 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1249
Keyword [en]
Neuropathy
National Category
Neurology
Identifiers
URN: urn:nbn:se:liu:diva-71215ISBN: 978-91-7393-118-2 (print)OAI: oai:DiVA.org:liu-71215DiVA: diva2:446477
Public defence
2011-10-28, Victoriasalen, Plan 10, Huvudblocket, Campus US, Linköpings universitet, Linköping, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2011-10-10 Created: 2011-10-06 Last updated: 2015-06-05Bibliographically approved
List of papers
1. Cryptogenic polyneuropathy: Clinical and neurophysiological findings
Open this publication in new window or tab >>Cryptogenic polyneuropathy: Clinical and neurophysiological findings
2005 (English)In: Journal of the peripheral nervous system, ISSN 1085-9489, E-ISSN 1529-8027, Vol. 10, no 1, 31-37 p.Article in journal (Refereed) Published
Abstract [en]

The purpose of this study was to describe the clinical and neurophysiological features of cryptogenic polyneuropathy in 168 patients in the neurological departments at three Swedish hospitals. The medical records of all patients aged 40-79 years with the diagnosis of cryptogenic polyneuropathy from 1993 to 2000 were analysed. One hundred and fourteen patients (68%) were men. The mean age at first symptom was 61 years and at diagnosis it was 64 years. Distal numbness (n=115, 68%) was the most common symptom, but some patients complained of pain, pedal paresthesiae, and impairment of balance. The most common clinical findings were decreased or lost proprioception or sense of vibration (n=135, 80%) and loss of ankle jerks (n=131, 78%). Neurography in 139 patients showed mixed sensorimotor polyneuropathy of axonal or mixed axonal and demyelinating type in 97 (70%). Cryptogenic polyneuropathy is a slowly progressive sensorimotor nerve lesion of mainly axonal type. Men are more often affected than women. Most patients have a minor or moderate severe polyneuropathy.

Keyword
Axonal, Electromyography, Idiopathic, Neurophysiology, Peripheral neuropathies
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-45496 (URN)10.1111/j.1085-9489.2005.10106.x (DOI)
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13
2. Occupational determinants of cryptogenic polyneuropathy
Open this publication in new window or tab >>Occupational determinants of cryptogenic polyneuropathy
Show others...
2006 (English)In: Neuroepidemiology, ISSN 0251-5350, E-ISSN 1423-0208, Vol. 26, no 4, 187-194 p.Article in journal (Refereed) Published
Abstract [en]

Objectives: The aim was to investigate different occupational and leisure time exposures as determinants for cryptogenic polyneuropathy. Methods: A case-referent study was conducted in Sweden including 232 cases of cryptogenic polyneuropathy 40-79 years of age at diagnosis who were enrolled from the out-patient neurology departments of 3 hospitals. From the population register 853 referents were randomly selected. Information on occupational and leisure time exposure was obtained from a postal questionnaire. The response rate was 71% for cases and for referents. Crude odds ratios (CORs) and logistic regression odds ratios (LORs) were calculated for exposures with 5 or more exposed cases and referents taken together. The reference category was defined as individuals unexposed to any of the occupational or leisure time risk factors in the questionnaire. Results: As expected, male sex and increasing age were significant determinants for cryptogenic polyneuropathy. Occupational exposures in men to Stoddard solvent, petrol exhausts, herbicides or hand and foot vibrations generated significantly increased CORs. LORs >3.50 were found in men for occupational exposure to sulphur dioxide, xylene, methyl ethyl ketone, herbicides and in women for occupational exposure to lead, nitrous oxide and insecticides. Only solvent exposure in leisure time remained significant in the regression analysis indicating that not only occupational exposures were of importance. Interactions between occupational and leisure time exposure were seen for several agents. Conclusions: Several known determinants for polyneuropathy, from animal studies and case reports, were confirmed. New determinants were also indicated, i.e. sulphur dioxide, xylene and methyl ethyl ketone. Copyright © 2006 S. Karger AG.

Keyword
Environmental exposure, Epidemiological factors, Polyneuropathy, cryptogenic, Solvents
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-48033 (URN)10.1159/000092405 (DOI)
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13
3. Health-related quality of life in patients with cryptogenic polyneuropathy compared with the general population
Open this publication in new window or tab >>Health-related quality of life in patients with cryptogenic polyneuropathy compared with the general population
2011 (English)In: DISABILITY AND REHABILITATION, ISSN 0963-8288, Vol. 33, no 7, 617-623 p.Article in journal (Refereed) Published
Abstract [en]

Purpose. To evaluate the quality of life (QOL) in patients with cryptogenic polyneuropathy. Method. Two validated instruments (SF-36 and EQ-5D) were sent to 86 patients with a 72% response rate (44 men, 18 women). As reference, 2721 individuals (1292 men, 1429 women; 59% response rate) from the general population responded to the same QOL instruments. Results. Compared to the general population, QOL was significantly more affected in patients with polyneuropathy concerning motor functions, with 42% of the patients reporting problems with walking, 7% having difficulties with washing and dressing, and 31% having problems with usual activities (work, study, household work, and family or leisure activities). The EQ-5D results showed that 85% of the patients were suffering from pain compared to 56% of the general population. Mental health was preserved among patients with polyneuropathy. Mobility was declining with increasing age in patients, but was not affected by disease duration. Conclusions. Our study showed that patients with cryptogenic polyneuropathy have a lower QOL compared to the general population, although mental health scores did not differ between the groups. This information may be helpful when explaining the disease and its impact on newly diagnosed patients.

Place, publisher, year, edition, pages
Informa Healthcare, 2011
Keyword
Activities of daily living, EuroQol, polyneuropathy, neurological disease, neuropathy
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-67316 (URN)10.3109/09638288.2010.505996 (DOI)000287451200008 ()
Available from: 2011-04-08 Created: 2011-04-08 Last updated: 2011-10-10
4. Polymorphisms of GSTT1, GSTM1 and EPHX genotypes in patients with cryptogenic polyneuropathy: a case control study
Open this publication in new window or tab >>Polymorphisms of GSTT1, GSTM1 and EPHX genotypes in patients with cryptogenic polyneuropathy: a case control study
Show others...
2011 (English)In: Brain and Behavior, ISSN 2162-3279, E-ISSN 2162-3279, Vol. 1, no 2, 135-141 p.Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to analyze whether polymorphisms for the null alleles of Glutathione S-Transferase Mu-1 (GSTM1) and Theta-1 (GSTT1) and a low activity genetic variation of epoxide hydrolase exon three (EPHX*3) affect the risk of developing polyneuropathy. The enzymes of these genes are important in the metabolism of toxic compounds. 79 patients with cryptogenic polyneuropathy (equivalent to chronic idiopathic axonal neuropathy) and 398 controls were tested for the genetic polymorphism. Medical records were reviewed to collect data regarding clinical findings at diagnosis, and exposure data was collected via questionnaires. The odds ratios (OR) for the null forms of GSTM1 and GSTT1 and the normal activity YY form of EPHX*3 were close to one except GSTT1, which reached 1.86. The highest risk of polyneuropathy was found in smokers with GSTT1 null, who had a 3.7 times increased risk. Interactions between genes were analyzed and confirmed the increased odds ratio for GSTT1, which was strongest if the patients had the low activity HH form of EPHX*3 (OR 2.37). Our hypothesis is that the GSTT1 null polymorphism may be related to an impaired metabolism of toxic substances that could lead to nerve damage in the peripheral nervous system.

Place, publisher, year, edition, pages
Hoboken, New Jersey, USA: John Wiley & Sons, Inc, 2011
Keyword
Polyneuropathy
National Category
Neurology
Identifiers
urn:nbn:se:liu:diva-70979 (URN)10.1002/brb3.26 (DOI)000209173700009 ()
Projects
kryptogen polyneuropati
Available from: 2011-10-03 Created: 2011-09-23 Last updated: 2017-12-08Bibliographically approved

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