n-Hexane and its metabolites are neurotoxic to animals and man. Studies have revealed a progressive neuropathy which affects the distal regions of motor and sensory peripheral nerves. This paper describes efforts to determine whether 2-hexanone or 2,5-hexanedione is more neurotoxic to rats when given in drinking water. Our results show that 2,5-hexanedione is more neurotoxic than 2-hexanone and that it first affects the distal axon. Concentrations of 20 mM produced no effects after 3 weeks but 40 mM increased distal latency after 2 weeks.

Indiana University-Purdue University Indianapolis (IUPUI) / The main focus of this study is to determine the impact of Set-Binding Factor 2 (SBF2) on human-derived neurons in the context of taxane-induced peripheral neuropathy. Taxane-induced peripheral neuropathy (TIPN) is a devastating survivorship issue for many cancer patients; SBF2 has been previously identified as a potential germline predictor that has been found to be significantly associated with severe TIPN in African American (AA) patients. The work described here provides ex vivo support for the use of SBF2 as a genotypic biomarker to identify a priori which patients are at a higher risk of manifesting severe TIPN. This study demonstrates that diminished expression of SBF2 exacerbated the effect of paclitaxel on viability and morphology and altered the functional response of a neuronal model exposed to paclitaxel treatment. Furthermore, transcriptomic work showed that reduced expression of SBF2 in a neuronal model treated with paclitaxel impacted the expression of genes that modulate stress-induced cell death and pain threshold. Altogether, these findings suggest that SBF2 plays a role in the development of TIPN. This work sheds light on the pathways potentially involving SBF2 that can be studied to further evaluate the function of this gene in neurons and its contribution to severe TIPN. Further functional approaches investigating these pathways will be pivotal in elucidating the underlying biological mechanism for this toxicity and identifying novel targeted therapeutic strategies to prevent or treat TIPN. / 2021-05-17

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is considered a rare autoimmune disorder which makes it difficult to accurately diagnose and creates a lot of opportunity for active research. With its wide array of presentations and even similarities to other neurological disorders, improvement must be made in the field of diagnostic methods in order to offer concise and effective treatments. As with many other neurological disorders, CIDP patients are at a higher risk for falls. The dual effect of gait impairment due to neuropathy and general effects of older age create a dangerous combination and increase the risk for falls. By increasing the accuracy with which physicians and health professionals predict falls in patients, they can effectively prevent serious injury and improve quality of life. Consequently, in order to predict the risk of falls, and therefore prevent severe injury, the ability to accurately access the specific qualities of the patient’s gait is critical. Without the ability to precisely identify patients’ particular gait impairment presentation it is very difficult to establish their risk for falls. The current methods of diagnoses focuses mainly on PROs (patient reported outcomes) which are often gathered through patient questionnaires. Previous research has shown that such methods are simply not detailed and patient specific enough to offer a complete picture of a patient’s condition. We believe ProtoKinetics Movement Analysis Software (PKMAS) is an objective, examiner independent measure of patients’ gait, and offers a method of quantifying patients’ functional gait outcomes in a way that is superior to the current standard of care procedures. Therefore, in this study we aim to reveal the shortcomings of current standard of care procedures in the diagnosis and treatment of CIDP, while also demonstrating the superior value of PKMAS in providing a detailed patient disease profile for CIDP afflicted individuals. Specifically, we demonstrate PKMAS’ increased ability to predict fall risk in CIDP patients, as compared with currently used methods. In this study PKMAS data was collected under two conditions: Dual Task and PWS (preferred walking speed). During each condition the patient was asked to walk across the Gait Map/Zeno Walkway as the ProtoKinetics Software collected detailed information about the patients’ gait. For PWS, patients were asked to walk across the map at a speed they were most comfortable at as PKMAS data was collected. For Dual Task, patients are asked to walk at their preferred walking speed while simultaneously doing a simple cognitive task, for instance, counting backwards from a hundred. This second condition is particularly important. The point of such a task is to mimic real-life walking. When we walk on a daily basis we are usually thinking or doing something else simultaneously, even if we may not be consciously aware of this. As such, comparing the results for PWS and Dual Task for patients can shine light onto their real-life gait experience. In order to do so, we measured the percent change in abilities between PWS and Dual Task walking. A greater change signifies greater gait impairment, and a change of greater than 15% places the patient at risk for falls. Among the PROs, INCAT is the one most often referred to in neurological standard of care and as such we focused on this particular questionnaire separately as well. To do so, t-tests were completed to demonstrate the lack of validity in scoring, by looking at the PKMAS data as compared between two INCAT scores. In this study we seek to demonstrate the superiority of ProtoKinetics Movement Analysis Software (PKMAS) over the current standard of care for CIDP patients. Specifically, in accurately evaluating patients’ gait and future fall risk. The ability to do so is vitally important for elderly patients who already suffer from decreased gait stability and the additional impact of CIDP can accentuate that risk.

京都大学 / 0048 / 新制・論文博士 / 博士(農学) / 乙第12876号 / 論農博第2803号 / 新制||農||1028(附属図書館) / 学位論文||H26||N4875(農学部図書室) / 31594 / (主査)教授 伏木 亨, 教授 保川 清, 教授 入江 一浩 / 学位規則第4条第2項該当 / Doctor of Agricultural Science / Kyoto University / DGAM

Neurofibromatosis type 2 is an autosomal dominant disease characterized by the formation of schwannomas and other peripheral neuropathies. The nf2 gene encodes the protein Schwannomin, or merlin. Schwannomin (Sch) is a membrane-cytoskeletal linking protein that suppresses cell proliferation at high cell density and modulates cell shape. Sch's tumor suppressive activity is regulated by its localization, conformation, and phosphorylation at serine 518 (S518). Sch's localization is dependent on binding the scaffold protein, paxillin. Phosphorylation of Sch at S518 regulates its conformation and tumor suppressor function. In a negative feedback loop, unphosphorylated Sch restricts cell proliferation downstream of Rac and p21-activated kinase (Pak), whereas Pak-induced phosphorylation inactivates Sch's ability to inhibit Pak and cell proliferation. Little is known about the function of the phosphorylated form of Sch, or the molecular mechanisms leading to its phosphorylation. Here we demonstrate that Sch-S518 phosphorylation is dependent on paxillin-binding and plasma membrane localization in SCs. Phosphorylation of Sch at the plasma membrane is mediated by Cdc42-Pak and results in altered SC morphology and polarity. Moreover, we have identified two extracellular stimuli that trigger Sch-S518 phosphorylation; these are neuregulin (NRG) and laminin, two potent activators of SC proliferation and myelination. NRG promotes Sch-S518 phosphorylation downstream of ErbB2/ErbB3 through PKA, whereas laminin-1 stimulation of β1 integrin promotes Pak- dependent phosphorylation of Sch-S518. Additionally, we find that Sch promotes process formation and elongation in primary and myelinating SCs, independent of Sch S518 phosphorylation. However, Sch phosphorylation was found to influence SC differentiation, as expression of an unphosphorylatable variant, Sch-S518A, facilitated SC myelination, whereas expression of a phospho-mimicking variant, Sch-S518D, reduced the SC's ability to myelinate. Together, these findings have identified receptor-mediated and paxillin-dependent pathways that regulate phosphorylation and inactivation of Sch's tumor suppressor function. Additionally, these results have elucidated novel normal functions for Sch during peripheral nerve development and myelination, and identify novel therapeutic targets for treatment of NF2 and other peripheral neuropathies.

The focus of this study was to assess the cardiovascular effects in hens of a single 2.5 mg/kg intramuscular injection of phenyl saligenin phosphate (PSP) into the breast muscle. Parameters were measured at 1, 3, 7, and 20 days post treatment. All hens developed clinical signs of delayed neuropathy by day 10 and these signs were maximal by day 20. Alterations of measured parameters were observed prior to the onset of clinical signs of organophosphorus-induced delayed neuropathy (OPIDN) (days 1, 3, and 7) as well as when maximal clinical signs were evident (days 15-21). Significant decreases in the activities of brain NTE and plasma cholinesterase as well as decreases in weight and the level of pcO2 and an increase in peripheral resistance were observed prior to evidence of clinical signs of OPIDN. When maximal signs of OPIDN were present, brain NTE and plasma cholinesterase were at control levels but brain cholinesterase was significantly increased. Significant decreases in body weight and arterial pCO2 and significant increases in limb venous flow, arterial blood pressure, and hematocrit were seen at this time. / Master of Science

Plantar heel pain is commonly encountered by clinicians. Various conditions, such as plantar fasciopathy, myofascial syndrome and entrapment of the tibial, plantar and calcaneal nerves at the tarsal tunnel can cause plantar heel pain. This diversity in aetiology makes the diagnosis and treatment challenging. There are limited studies on pain mechanisms in patients with planter heel pain. There is no gold criterion standard for the diagnosis. Although various interventions have been reported, no specific treatment approach has yet been identified as being most effective. The first aim of this thesis was to critically appraise the literature on plantar heel pain of neural origin. Various databases were searched for peer-reviewed articles that predominantly focused on neurogenic plantar heel pain or that discussed relevant biomechanics of the tibial, plantar and calcaneal nerves. This review revealed inconsistency in the literature regarding the diagnosis and treatment of neurogenic plantar heel pain. There also was a lack of evidence for treatment approaches although the majority of patients with plantar heel pain are reported to improve with conservative treatment. The second aim of this thesis was to examine the biomechanical effects of clinical tests and combination of movements on various structures associated with plantar heel pain. This aim was achieved through cadaver studies (Study 1–3), in which strain in the plantar fascia and the nerves of the lower limb, and excursion of the nerves were measured during various movements and positions of the lower limb. Study 1 examined the Dorsiflexion-eversion test used to diagnose tarsal tunnel syndrome (TTS) and the Windlass test for plantar fasciopathy given the similarity between both tests. Both the Dorsiflexion-eversion and Windlass tests significantly increased strain in the structures that are commonly associated with plantar heel pain (the tibial and plantar nerves and plantar fascia). This suggests that the usefulness of the Dorsiflexion-eversion and Windlass tests in the differential diagnosis of plantar heel pain might be limited. Study 2 investigated the influence of different positions in adjacent joints on nerve biomechanics during ankle and toe movement. Increased strain in the tibial nerve at the ankle and plantar nerves associated with ankle and toe movement was significantly higher when the nervous system was pre-tensioned at a more proximal joint. Strain was even higher when the nerve bed was pre-tensioned at two joints. Study 3 examined a modified straight leg raising (SLR) test in which ankle dorsiflexion is performed before hip flexion. This test has been suggested to diagnose distal neuropathies such as TTS. During the modified SLR, the excursion and strain in the sciatic nerve associated with hip flexion were transmitted distally along the nerve from the hip to the foot. As a result, the strain in the nerves around the foot and ankle increased significantly during hip flexion. This movement did not affect plantar fascia strain. Consequently, the modified SLR may be a useful test to differentially diagnose plantar heel pain. This test warrants future research to evaluate its clinical use in patients with neurogenic plantar heel pain. The third aim of this thesis was to determine the reliability of high-resolution ultrasound for measuring the cross-sectional area of the tibial nerve at the tarsal tunnel and to compare the tibial nerve size between people with and without plantar heel pain. Study 4 investigated intra and intertester reliability in 10 participants without plantar heel pain by calculating intraclass correlation coefficients, measurement error and smallest detectable difference (SDD). Intra and intertester reliability were excellent, with very small measurement error and SDD. Tibial nerve enlargement in an individual patient by as little as 1.8 mm2 can be detected reliably with high-resolution ultrasound. The use of average value of three scans is recommended to compare between the involved and uninvolved side. Differences in the nerve size between 26 patients with plantar heel pain and 20 control participants were also analysed. There was no significant difference in tibial nerve size between both groups. Future research is needed to investigate the tibial nerve size in patients with proven TTS using ultrasonography. The fourth aim of this thesis was to investigate the characteristics of plantar heel pain through Study 5 for the same group of patients and control participants as in Study 4. Several self-report measures on pain and quality of life were used. Clinical tests and quantitative sensory tests (QST) were performed at local and remote sites on the involved and uninvolved side in the patients and on one side in the control participants. In the patients, mechanical hyperalgesia was the main finding as demonstrated by changes in palpation and pressure pain threshold. Other findings were changes in current thresholds, vibration threshold and thermal perception thresholds. These results suggest the existence of sensory changes that likely indicates change in peripheral and central pain processing. It is recommended to utilise a multidimensional pain assessment for patients with plantar heel pain. The findings in this thesis are important for the diagnosis and treatment of plantar heel pain. For future research, the results suggest to use fresh cadavers when investigating biomechanics of the clinical tests and nerve gliding exercises that are used for patients with plantar heel pain. It is also suggested to evaluate the cross-sectional area of the tibial nerve at the tarsal tunnel, the QSTs and all other diagnostic measurements in this thesis in patients with neurogenic plantar heel pain or patients with TTS.

Segundo dados de 2012 da Sociedade Brasileira de Diabetes, se estima que cerca de 6% da população brasileira tenha diabetes e cerca de 7 a 8% tenha pré-diabetes. A neuropatia diabética é a complicação mais frequente dessa doença podendo já ocorrer no pré-diabetes. O início da neuropatia diabética é precoce e exibe grande variabilidade de manifestações clínicas, incluindo o comprometimento de diversas fibras nervosas somáticas e autonômicas. O diagnóstico tardio da neuropatia em diabéticos está associado à maior incidência de complicações como, por exemplo, ulcerações e amputações típicas do “pé diabético” e risco cardiovascular aumentado, incluindo a morte súbita. Dados como os citados acima motivaram a presente pesquisa, que se propõe a associar métodos diagnósticos não invasivos, disponíveis em nosso meio, a protocolos de investigação já recomendados pela comunidade científica internacional para neuropatia diabética. Aplicou-se um extenso protocolo de testes com finalidade de rastreamento da neuropatia somática e autonômica em três grupos de indivíduos: grupo DM (com diabetes melitus tipo 2), grupo Pré-DM, pré diabético e grupo C, de controles saudáveis. O teste em estudo foi a Termografia Computadorizada por Infravermelho, método sem contato que capta a emissão da radiação infravermelha pelo corpo humano e que, com auxílio de softwares, possibilita medições de temperatura em graus Celsius. A termografia foi testada na região plantar, utilizando-se de duas variáveis: Índice de Recuperação Térmica e presença ou não de Anisotermia Interdigital. O padrão de referência para a Termografia plantar foram os testes cardíacos de Variabilidade da Frequência Cardíaca. Pesquisas prévias demonstraram uma relação estreita entre a Neuropatia Autonômica Cardíaca (NAC) e neuropatia autonômica sistêmica. Quanto à reprodutibilidade das medidas termográficas, encontrou-se que as medidas relativas de diferenças de temperatura (Δt) são reprodutíveis nos diferentes grupos estudados e são preferíveis às medições de temperatura absoluta, confirmando a literatura. A presença de Anisotermia Interdigital parece ser o teste mais apropriado para identificar neuropatia em suas formas iniciais no grupo com diabetes e pré- diabetes, pela simplicidade de sua aplicação e pela sua boa sensibilidade e especificidade. Com a inclusão da termografia plantar em programas de rastreamento de neuropatia diabética pode-se prever um diagnóstico mais precoce e, assim, um controle mais efetivo de fatores de risco para esta patologia bem como tratamento mais precoce. / According to 2012 data from the Brazilian Society of Diabetes it is estimated that about 6% of the population have diabetes and about 7 to 8% have pre-diabetes. Diabetic neuropathy is the most common complication of this disease and may already occur in the pre-diabetes. The onset of diabetic neuropathy is early and shows great variability of clinical manifestations, including the commitment of various somatic and autonomic nerve fibers. Delayed diagnosis of diabetic neuropathy is associated with higher incidence of complications such as ulcerations and amputations, typical "diabetic foot" and increased of cardiovascular risk, including sudden death. Data such as those mentioned above have motivated this research, which aims to involve non-invasive diagnostic methods available in our area, the research protocols as recommended by the international scientific community for diabetic neuropathy. We applied an extensive testing protocol with the purpose of tracking somatic and autonomic neuropathy in three different groups: DM group, with type 2 diabetes, Pre-DM group, pre diabetic, and C, healthy controls. The test under study was Computerized Infrared Thermography, a no contact method that captures the emission of infrared radiation by the human body and, with the help of software, can make measurements of temperature in degrees Celsius. Thermography was tested in the plantar region, using two variables: Thermal Recovery Index and presence or absence of Interdigital Anisothermal. The reference standard for the plantar thermography tests were cardiac Heart Rate Variability. Previous studies have demonstrated a close relationship between Cardiac Autonomic Neuropathy (CAN) and systemic autonomic neuropathy. The reproducibility of the thermographic measurements was found that the relative measures of temperature differences (Δt) are reproducible in different groups, and are preferable to absolute temperature measurements, confirming the literature. The presence of Interdigital Anisothermal seems to be the most appropriate test to identify neuropathy in their initial forms in the group with diabetes and pre diabetes, because the simplicity of its application and its good sensitivity and specificity. With the addition of plantar thermography in the screening of diabetic neuropathy we may predict an earlier diagnosis and thus a more effective control of risk factors for this disease and earlier treatment.

Segundo dados de 2012 da Sociedade Brasileira de Diabetes, se estima que cerca de 6% da população brasileira tenha diabetes e cerca de 7 a 8% tenha pré-diabetes. A neuropatia diabética é a complicação mais frequente dessa doença podendo já ocorrer no pré-diabetes. O início da neuropatia diabética é precoce e exibe grande variabilidade de manifestações clínicas, incluindo o comprometimento de diversas fibras nervosas somáticas e autonômicas. O diagnóstico tardio da neuropatia em diabéticos está associado à maior incidência de complicações como, por exemplo, ulcerações e amputações típicas do “pé diabético” e risco cardiovascular aumentado, incluindo a morte súbita. Dados como os citados acima motivaram a presente pesquisa, que se propõe a associar métodos diagnósticos não invasivos, disponíveis em nosso meio, a protocolos de investigação já recomendados pela comunidade científica internacional para neuropatia diabética. Aplicou-se um extenso protocolo de testes com finalidade de rastreamento da neuropatia somática e autonômica em três grupos de indivíduos: grupo DM (com diabetes melitus tipo 2), grupo Pré-DM, pré diabético e grupo C, de controles saudáveis. O teste em estudo foi a Termografia Computadorizada por Infravermelho, método sem contato que capta a emissão da radiação infravermelha pelo corpo humano e que, com auxílio de softwares, possibilita medições de temperatura em graus Celsius. A termografia foi testada na região plantar, utilizando-se de duas variáveis: Índice de Recuperação Térmica e presença ou não de Anisotermia Interdigital. O padrão de referência para a Termografia plantar foram os testes cardíacos de Variabilidade da Frequência Cardíaca. Pesquisas prévias demonstraram uma relação estreita entre a Neuropatia Autonômica Cardíaca (NAC) e neuropatia autonômica sistêmica. Quanto à reprodutibilidade das medidas termográficas, encontrou-se que as medidas relativas de diferenças de temperatura (Δt) são reprodutíveis nos diferentes grupos estudados e são preferíveis às medições de temperatura absoluta, confirmando a literatura. A presença de Anisotermia Interdigital parece ser o teste mais apropriado para identificar neuropatia em suas formas iniciais no grupo com diabetes e pré- diabetes, pela simplicidade de sua aplicação e pela sua boa sensibilidade e especificidade. Com a inclusão da termografia plantar em programas de rastreamento de neuropatia diabética pode-se prever um diagnóstico mais precoce e, assim, um controle mais efetivo de fatores de risco para esta patologia bem como tratamento mais precoce. / According to 2012 data from the Brazilian Society of Diabetes it is estimated that about 6% of the population have diabetes and about 7 to 8% have pre-diabetes. Diabetic neuropathy is the most common complication of this disease and may already occur in the pre-diabetes. The onset of diabetic neuropathy is early and shows great variability of clinical manifestations, including the commitment of various somatic and autonomic nerve fibers. Delayed diagnosis of diabetic neuropathy is associated with higher incidence of complications such as ulcerations and amputations, typical "diabetic foot" and increased of cardiovascular risk, including sudden death. Data such as those mentioned above have motivated this research, which aims to involve non-invasive diagnostic methods available in our area, the research protocols as recommended by the international scientific community for diabetic neuropathy. We applied an extensive testing protocol with the purpose of tracking somatic and autonomic neuropathy in three different groups: DM group, with type 2 diabetes, Pre-DM group, pre diabetic, and C, healthy controls. The test under study was Computerized Infrared Thermography, a no contact method that captures the emission of infrared radiation by the human body and, with the help of software, can make measurements of temperature in degrees Celsius. Thermography was tested in the plantar region, using two variables: Thermal Recovery Index and presence or absence of Interdigital Anisothermal. The reference standard for the plantar thermography tests were cardiac Heart Rate Variability. Previous studies have demonstrated a close relationship between Cardiac Autonomic Neuropathy (CAN) and systemic autonomic neuropathy. The reproducibility of the thermographic measurements was found that the relative measures of temperature differences (Δt) are reproducible in different groups, and are preferable to absolute temperature measurements, confirming the literature. The presence of Interdigital Anisothermal seems to be the most appropriate test to identify neuropathy in their initial forms in the group with diabetes and pre diabetes, because the simplicity of its application and its good sensitivity and specificity. With the addition of plantar thermography in the screening of diabetic neuropathy we may predict an earlier diagnosis and thus a more effective control of risk factors for this disease and earlier treatment.

Segundo dados de 2012 da Sociedade Brasileira de Diabetes, se estima que cerca de 6% da população brasileira tenha diabetes e cerca de 7 a 8% tenha pré-diabetes. A neuropatia diabética é a complicação mais frequente dessa doença podendo já ocorrer no pré-diabetes. O início da neuropatia diabética é precoce e exibe grande variabilidade de manifestações clínicas, incluindo o comprometimento de diversas fibras nervosas somáticas e autonômicas. O diagnóstico tardio da neuropatia em diabéticos está associado à maior incidência de complicações como, por exemplo, ulcerações e amputações típicas do “pé diabético” e risco cardiovascular aumentado, incluindo a morte súbita. Dados como os citados acima motivaram a presente pesquisa, que se propõe a associar métodos diagnósticos não invasivos, disponíveis em nosso meio, a protocolos de investigação já recomendados pela comunidade científica internacional para neuropatia diabética. Aplicou-se um extenso protocolo de testes com finalidade de rastreamento da neuropatia somática e autonômica em três grupos de indivíduos: grupo DM (com diabetes melitus tipo 2), grupo Pré-DM, pré diabético e grupo C, de controles saudáveis. O teste em estudo foi a Termografia Computadorizada por Infravermelho, método sem contato que capta a emissão da radiação infravermelha pelo corpo humano e que, com auxílio de softwares, possibilita medições de temperatura em graus Celsius. A termografia foi testada na região plantar, utilizando-se de duas variáveis: Índice de Recuperação Térmica e presença ou não de Anisotermia Interdigital. O padrão de referência para a Termografia plantar foram os testes cardíacos de Variabilidade da Frequência Cardíaca. Pesquisas prévias demonstraram uma relação estreita entre a Neuropatia Autonômica Cardíaca (NAC) e neuropatia autonômica sistêmica. Quanto à reprodutibilidade das medidas termográficas, encontrou-se que as medidas relativas de diferenças de temperatura (Δt) são reprodutíveis nos diferentes grupos estudados e são preferíveis às medições de temperatura absoluta, confirmando a literatura. A presença de Anisotermia Interdigital parece ser o teste mais apropriado para identificar neuropatia em suas formas iniciais no grupo com diabetes e pré- diabetes, pela simplicidade de sua aplicação e pela sua boa sensibilidade e especificidade. Com a inclusão da termografia plantar em programas de rastreamento de neuropatia diabética pode-se prever um diagnóstico mais precoce e, assim, um controle mais efetivo de fatores de risco para esta patologia bem como tratamento mais precoce. / According to 2012 data from the Brazilian Society of Diabetes it is estimated that about 6% of the population have diabetes and about 7 to 8% have pre-diabetes. Diabetic neuropathy is the most common complication of this disease and may already occur in the pre-diabetes. The onset of diabetic neuropathy is early and shows great variability of clinical manifestations, including the commitment of various somatic and autonomic nerve fibers. Delayed diagnosis of diabetic neuropathy is associated with higher incidence of complications such as ulcerations and amputations, typical "diabetic foot" and increased of cardiovascular risk, including sudden death. Data such as those mentioned above have motivated this research, which aims to involve non-invasive diagnostic methods available in our area, the research protocols as recommended by the international scientific community for diabetic neuropathy. We applied an extensive testing protocol with the purpose of tracking somatic and autonomic neuropathy in three different groups: DM group, with type 2 diabetes, Pre-DM group, pre diabetic, and C, healthy controls. The test under study was Computerized Infrared Thermography, a no contact method that captures the emission of infrared radiation by the human body and, with the help of software, can make measurements of temperature in degrees Celsius. Thermography was tested in the plantar region, using two variables: Thermal Recovery Index and presence or absence of Interdigital Anisothermal. The reference standard for the plantar thermography tests were cardiac Heart Rate Variability. Previous studies have demonstrated a close relationship between Cardiac Autonomic Neuropathy (CAN) and systemic autonomic neuropathy. The reproducibility of the thermographic measurements was found that the relative measures of temperature differences (Δt) are reproducible in different groups, and are preferable to absolute temperature measurements, confirming the literature. The presence of Interdigital Anisothermal seems to be the most appropriate test to identify neuropathy in their initial forms in the group with diabetes and pre diabetes, because the simplicity of its application and its good sensitivity and specificity. With the addition of plantar thermography in the screening of diabetic neuropathy we may predict an earlier diagnosis and thus a more effective control of risk factors for this disease and earlier treatment.