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.