Thermal threshold tester, a useful tool for detection of very early nerve damage--determination of normal values in a healthy population unexposed to Mycobacterium leprae and its application in the A9 study.

INTRODUCTION: In Ethiopia, a large percentage of leprosy patients present with established nerve damage. Present techniques for measuring nerve function impairment show no abnormality until 30% of nerve axons are destroyed. Nerve damage in leprosy occurs first in small diameter unmyelinated fibres, then in small myelinated fibres, and much later in large myelinated fibres. The Thermal Threshold Tester (TTT) was used to measure function in nerves carrying heat sensation (unmyelinated C fibres) and cold sensation (thinly myelinated Adelta fibres). PATIENTS: A school and community health survey, assessed 234 students and adults aged 10-75 years from Chencha Woreda, an area with low endemicity of leprosy. A group of students in Addis Ababa, exposed to leprosy, were also studied. RESULTS: The upper limits of normal were: wrist hot threshold (HT): 0.17 degrees C, wrist cold threshold (CT): 0.19 degrees C, foot HT: 0.17 degrees C and foot CT: 0.20 degrees C. Both the leprosy group and also controls in Addis Ababa showed significantly increased TTT values. CONCLUSION: The TTT detects nerve damage before clinical neuritis occurs and is a valuable tool for early diagnosis of leprosy or detecting clinical relapse of treated patients and for sequential and quantitative monitoring of small diameter nerve function in other neuropathies.

Peripheral nerves and nerve function in highland Ethiopians.

INTRODUCTION: In Ethiopia, where leprosy has been one of the commonest causes of peripheral nerve enlargement and dysfunction, nerve functions are assessed by a battery of "physical" tests. Voluntary Muscle Test (VMT) and Graded Sensory Skin Test (STG) are standard tests used for persons with leprosy. Normal values for nerve function tests (NFT) in Highland Ethiopians have not previously been determined, but have been taken from standard textbooks. In this study, normal values for NFT were determined by VMT, STG, 2-Point Discrimination Tests both static and moving, and Thermal Threshold Test. Physiological enlargement of right ulnar and radial-cutaneous nerves has been recognised by some leprologists, but we were unable to find written records in the available medical literature. MATERIALS: We assessed 236 students and adults aged 10-75 years from Chencha Woreda, an area with low endemicity of leprosy for 25-30 years. Two affected by leprosy were excluded from the analysis. RESULTS: NFT thresholds were affected variously by age, exercise and skin factors, domicile and exposure to organo-phosphates. Nerve size was affected by age, gender, exercise, skin fold thickness, body mass index. Exercise related physiological nerve enlargement has been documented. CONCLUSION: These data provide a usefull baseline for investigation of peripheral nerve function in highland Ethiopians.

Low level exposures to organophosphorus esters may cause neurotoxicity.

A large number of published studies support the notion that long term, low level (LTLL) exposure to organophosphorus (OP) esters may cause neurological and neurobehavioral effects. In order to differentiate these from other effects of OP such as the acute cholinergic episodes, intermediate syndrome and organophosphate induced delayed neuropathy (OPIDN), the term Chronic Organophosphate Induced Neuropsychiatric Disorder (COPIND) will be used purely for the ease of reference. The question addressed in this particular review is whether LTLL exposure to OP may produce neurotoxicity. The profile and the degree of overlap of the various components of COPIND have been addressed elsewhere and description of the possible mechanisms for COPIND is outside the scope of this article. COPIND can be classified under two headings; those produced following one or more acute clinical cholinergic episodes, and those produced without such preceding attacks. With regards to the first group, there are a total of 11 studies, all of which support the existence of a positive link between exposure to OP and neurotoxicity; six of these studies comprise descriptions of large numbers of cases without controls while five additional studies employ controls. Appearance of neurotoxicity does not seem to be related to the number or the intensity of acute cholinergic attacks. With regards to the second group, three types of studies can be identified. Firstly, there are five studies using experimental animals, all of which showed a positive link between OP and neurotoxicity. Secondly, a total of seven case studies without controls, some involving large numbers of patients, concluded that there is a positive link between OP and neurotoxicity. Thirdly, 19 studies investigated such a link using cases and control groups. Of these, 15 studies (about 80%) showed a positive link and only four failed to identify any link between OP and neurotoxicity. Annotation of all the 19 studies according to ideal set of criteria showed that only a few of these comply with the rules of excellence and all of these few showed a positive link. Furthermore, the only study carried out blind without the identification of subjects or controls, showed a positive link between OP and neurotoxicity. This blind study estimated the overall incidence of a form of neurotoxicity in people exposed to OP to be about 40 times higher than in the general population. The type of neurological involvement was unique and different from OP induced syndromes previously described. The profile of the neurological involvement was similar to that in COPIND whether or not preceded by acute cholinergic episodes, thus providing further evidence that these two neuropathies probably share a similar mechanism. There is a characteristic pattern of involvement of 15 functional indices of the autonomic nervous system examined in our laboratory. There are, in addition, preferential anatomical sites of target organs affected, selective preservation of cholinergic function within the same neuropathy-positive site, and evidence of mal-function of cardiac chemoreceptors in patients exposed to OP. The peripheral nerve involvement in OP exposure is predominantly sensory in nature affecting both small and large fibre populations. Neurobehavioral involvement of mainly cognitive dysfunction and other features are also described in other studies. The weight of current evidence is therefore very much in favor of the motion that chronic low-level exposure to OP produces neurotoxicity. Criticisms levelled against this motion are unfounded and probably misconceived.