Corneal Sub-Basal Nerve Plexus in Non-Diabetic Small Fiber Polyneuropathies and the Diagnostic Role of In Vivo Corneal Confocal Microscopy.

In vivo corneal confocal microscopy (IVCM) allows the immediate analysis of the corneal nerve quantity and morphology. This method became, an indispensable tool for the tropism examination, as it evaluates the small fiber plexus in the cornea. The IVCM provides us with direct information on the health of the sub-basal nerve plexus and indirectly on the peripheral nerve status. It is an important tool used to investigate peripheral polyneuropathies. Small-fiber neuropathy (SFN) is a group of neurological disorders characterized by neuropathic pain symptoms and autonomic complaints due to the selective involvement of thinly myelinated Aδ-fibers and unmyelinated C-fibers. Accurate diagnosis of SFN is important as it provides a basis for etiological work-up and treatment decisions. The diagnosis of SFN is sometimes challenging as the clinical picture can be difficult to interpret and standard electromyography is normal. In cases of suspected SFN, measurement of intraepidermal nerve fiber density through a skin biopsy and/or analysis of quantitative sensory testing can enable diagnosis. The purpose of the present review is to summarize the current knowledge about corneal nerves in different SFN. Specifically, we explore the correlation between nerve density and morphology and type of SFN, disease duration, and follow-up. We will discuss the relationship between cataracts and refractive surgery and iatrogenic dry eye disease. Furthermore, these new paradigms in SFN present an opportunity for neurologists and clinical specialists in the diagnosis and monitoring the peripheral small fiber polyneuropathies.

Prevalencia de Neuropatía periférica de pequeñas fibras asociada a retinopatía en diabéticos tipo 2: Uso prueba biomédica por imagen termográfica

Introducción: La neuropatía periférica diabética de fibras delgadas (NPD-fd) son diagnosticadas por pruebas biomédicas vasomotoras cuyo fundamento es la alteración de la termorregulación de la piel. Objetivos: Calcular la prevalencia y los factores asociados a NPD-fd usando imagen termográfica (IT). Métodos: Se realizó un estudio observacional, transversal analítico en una unidad especializada en el ámbito de la atención primaria, en el que se avaluó pacientes con diabetes mellitus tipo 2 mediante pruebas neurológicas periféricas como la sensibilidad táctil y vibratoria para el diagnóstico de NPD de fibras gruesas (NPDfg) y la termorregulación pasiva por IT para la NPD-fd . Ésta última se realizó en la planta del pie utilizando una cámara termográfica en la consulta ambulatoria, evaluando 5 mediciones termográficas plantares por sujeto. Luego, la asociación entre diabéticos con y sin NPD-fd fue analizada respecto a género, edad, tiempo de enfermedad diabética, tipo de tratamiento diabético, hipertensión, retinopatía, nefropatía, dieta baja en carbohidratos, actividad física, síntoma dolor y IMC. Resultados: Se estudiaron 304 pacientes con diabetes mellitus tipo 2, una edad promedio de 65.07±11.39 años, en su mayoría de sexo masculino, encontrándose una NPD-fg en 14.8 %, NPD-fd en 27.3 % y ambas NPD en 34.9%. La asociación de la NPD-fd fue únicamente con el factor de la presencia de retinopatía (α=0,02, C= 0.18). Conclusiones: Se encontró una alta prevalencia de NPD-fd usando una imagen termográfica que estuvo asociado a la presencia de retinopatía.

Introduction: Small fibers diabetic peripheral neuropathy (DPN-sf) are diagnosed by biomedical vasomotor tests whose foundation is altered skin thermoregulation. Objectives: To estimate the prevalence and factors associated with DPN-sf using thermographic imaging (TI). Methods: An observational, cross-sectional, analytical study was performed in a specialized unit in the primary care setting, in which patients with type 2 diabetes mellitus were assessed by peripheral neurological tests such as tactile and vibratory sensitivity for the diagnosis of large fibers peripheral neuropathy (DPN-lf) and passive thermoregulation by TI for DPN-sf .The latter was performed on the sole using a thermographic camera in the outpatient clinic, evaluating 5 plantar thermographic measurements per subject. Then, the association between diabetics with and without DPN-sf was analyzed concerning gender, age, time of diabetic disease, type of diabetic treatment, hypertension, retinopathy, nephropathy, low carbohydrate diet, physical activity, pain symptom, and BMI. Results: 304 patients with type 2 diabetes mellitus were studied, mean age of 65.07±11.39 years, mostly male, finding DPN-lf in 14.8 %, DPN-sf in 27.3 %, and both NPD in 34.9%. The association of DPN-sf was only with the factor of the presence of retinopathy (α=0.02, C= 0.18). Conclusions: We found a high prevalence of DPN-sf using thermographic imaging that was associated with the presence of retinopathy.

Small fiber neuropathy as a complication of SARS-CoV-2 vaccinations.

Generally, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations are not free of side effects. A rarely reported adverse reaction to SARS-CoV-2 vaccinations is small fiber neuropathy (SFN). Here, we present three patients with SFN after the second dose of messenger ribonucleic acid-based SARS-CoV-2 vaccines. Data for this study were collected via the self-made platform "Pubbly" for reporting side effects of SARS-CoV-2 vaccinations. Three patients with post-SARS-CoV-2 vaccination SFN were identified: a 40 yo Caucasian female (patient 1), a 52 yo Caucasian female (patient 2), and a 32 yo Caucasian female (patient 3). Patient 1 complained about fatigue, dizziness, flushing, palpitations, diarrhea, muscle weakness, and gait disturbance 10 days after the second Pfizer jab. Patient 2 reported dizziness, balance problems, brain fog, palpitations, dysphagia, and sleep problems. Patient 3 complained about profound fatigue, brain fog, vertigo, pre-syncopal sensations, hair loss, chest pain, dyspnea, palpitations, paresthesias, irregular menstrual cycles, muscle weakness, and hives 1 day after the second Moderna dose. All three patients underwent skin biopsy upon which SFN was diagnosed. Patient 1 profited from immunoglobulins, but patient 2 did not require any treatment. Symptoms in patient 3 resolved upon symptomatic treatment. Despite treatment, patient 1 did not completely recover. SFN can be a rare side effect of SARS-CoV-2 vaccinations. Post-SARS-CoV-2 vaccination SFN can be mild or severe and may or may not require treatment. Post-SARS-CoV-2 vaccination SFN is most likely immune-mediated as it responds to intravenous immunoglobulins.

Review of techniques useful for the assessment of sensory small fiber neuropathies: Report from an IFCN expert group.

Nerve conduction studies (NCS) are an essential aspect of the assessment of patients with peripheral neuropathies. However, conventional NCS do not reflect activation of small afferent fibers, including Aδ and C fibers. A definitive gold standard for laboratory evaluation of these fibers is still needed and therefore, clinical evaluation remains fundamental in patients with small fiber neuropathies (SFN). Several clinical and research techniques have been developed for the assessment of small fiber function, such as (i) microneurography, (ii) laser evoked potentials, (iii) contact heat evoked potentials, (iv) pain-related electrically evoked potentials, (v) quantitative thermal sensory testing, (vi) skin biopsy-intraepidermal nerve fiber density and (vii) corneal confocal microscopy. The first five are physiological techniques, while the last two are morphological. They all have advantages and limitations, but the combined use of an appropriate selection of each of them would lead to gathering invaluable information for the diagnosis of SFN. In this review, we present an update on techniques available for the study of small afferent fibers and their clinical applicability. A summary of the anatomy and important physiological aspects of these pathways, and the clinical manifestations of their dysfunction is also included, in order to have a minimal common background.

Small Fiber Neuropathy in Diabetes Polyneuropathy: Is It Time to Change?

Diabetes polyneuropathy is an important complication of diabetes polyneuropathy, and its notable sequelae of foot ulceration, autonomic dysfunction, and neuropathic pain are associated with significant morbidity and mortality. Despite the major impact on quality of life and health economic costs, it remains underdiagnosed until late in its natural history, and there is lack of any intervention that can reverse its clinical progress. Assessment of small fiber neuropathy (SFN) in diabetes offers an opportunity to detect abnormalities at an early stage so that both interventional studies and preventative measures can be enacted to prevent progression to the devastating complications of foot ulceration and cardiac dysautonomic death. Over the last two decades, significant advances have been made in understanding the pathophysiology of diabetes neuropathy and its assessment. In this review, we discuss limitations of the screening methods recommended in current clinical guidelines which are based on large nerve fiber assessments. Thereafter, we discuss in detail the various methods currently available to assess small fiber structure and function and examine their individual strength and limitations. Finally, we discuss the reasons why despite the considerable body of evidence available, legislators and global experts have yet to incorporate the assessment of SFN as routine clinical surveillance in diabetes management. We hope that these insights will stimulate further discussion and be instrumental in the early adoption of these methods so as to reduce the burden of complications arising due to diabetes polyneuropathy.

Synaptic Effect of Aδ-Fibers by Pulse-Train Electrical Stimulation.

Electrical stimulation of specific small fibers (Aδ- and C-fibers) is used in basic studies on nociception and neuropathic pain and to diagnose neuropathies. For selective stimulation of small fibers, the optimal stimulation waveform parameters are an important aspect together with the study of electrode design. However, determining an optimal stimulation condition is challenging, as it requires the characterization of the response of the small fibers to electrical stimulation. The perception thresholds are generally characterized using single-pulse stimulation based on the strength-duration curve. However, this does not account for the temporal effects of the different waveforms used in practical applications. In this study, we designed an experiment to characterize the effects of multiple pulse stimulation and proposed a computational model that considers electrostimulation of fibers and synaptic effects in a multiscale model. The measurements of perception thresholds showed that the pulse dependency of the threshold was an exponential decay with a maximum reduction of 55%. In addition, the frequency dependence of the threshold showed a U-shaped response with a reduction of 25% at 30 Hz. Moreover, the computational model explained the synaptic effects, which were also confirmed by evoked potential recordings. This study further characterized the activation of small fibers and clarified the synaptic effects, demonstrating the importance of waveform selection.

The impact of chronic co-exposure to different heavy metals on small fibers of peripheral nerves. A study of metal industry workers.

BACKGROUND: Chronic exposure to heavy metals affects various organs, among them the brain and peripheral nerves. Polyneuropathy is mainly length-dependent with predominantly sensory symptoms. There have been few studies on small fiber neuropathy due to heavy metal intoxication. METHODS: We investigated 41 metal industry workers, mean age 51.3 ± 10.5 years, with at least 5 years' professional exposure to heavy metals, and 36 age- and sex-matched healthy controls. We performed neurological examinations, and assessed blood levels of cadmium, lead, and zinc protoporphyrin, urine levels of arsenic, standard, sensory and motor electrophysiological tests in the ulnar and peroneal nerves, sympathetic skin responses from the palm and foot, and quantitative sensation testing from dermatomes C8 and S1. DISCUSSION: The results of standard conduction tests of all nerves significantly differed between groups. The latency of sympathetic skin responses achieved from the foot was also statistically significantly prolonged in the study group. Significant differences were seen in both C8 and S1 regions for temperature and pain thresholds, and for vibratory threshold only in the S1 region, while the dispersions of low and high temperatures were important exclusively in the C8 region. CONCLUSIONS: We can conclude that co-exposure to many heavy metals results in explicit impairment of peripheral nerves. The lesion is more pronounced within small fibers and is predominantly connected with greater impairment of temperature-dependent pain thresholds. The evaluation of small fiber function should be considered in the early diagnosis of toxic polyneuropathy or in low-dose exposure to heavy metals.

A Synoptic Overview of Neurovascular Interactions in the Foot.

Diabetes is a worldwide public health concern as it is associated with various complications. One of the major complications of diabetes is diabetic foot syndrome that results in catastrophic events such as ulceration and amputation. Therefore, the main four strategies of diabetic foot care involve risk prediction, prevention, and early diagnosis and prompt intervention. The drivers of ulceration are multifactorial, and importantly, include microcirculatory changes in the diabetic skin. Cutaneous microcirculation on the foot is greatly influenced by the small fibers which mediate thermal sensation and pain perception in addition to sympathetic activities such as thermoregulation and vasodilation. The interdependence between the neurovascular elements means with the loss of small fiber functions, the corresponding microcirculatory responses may be compromised. Thus, it can be hypothesized that the impairment of the microcirculation may follow the order of the corresponding small fiber nerve dysfunction or vice versa. In this review, select neurovascular investigations that inform the cutaneous microcirculatory and small fiber nerve function in response to pain, cold, and heat and pressure stimuli are reviewed and discussed in this order of sensory loss: the loss of pain, cold, warmth, touch and deep pressure sensation. We also discuss the neurological and vascular characteristics of each of these neurovascular responses. This review highlights the influence of small fibers on cutaneous microcirculation and the need for prospective studies that can determine the course of microcirculatory impairment over time. This, in turn, may help clarify the exact role of microcirculatory changes in the pathway of ulceration. The insights from this review can be pertinent to understand key microcirculatory disturbances and given that the microcirculatory impairment develops at an early stage, relevant interventions can be implemented to possibly reverse or regress the course of the disease. Therefore, knowledge of the neurovascular interactions aids to map the disease progression for early diagnosis and prevention of adverse complications.

Levodopa-Induced Neuropathy: A Systematic Review.

BACKGROUND: Clinical, neurophysiological, and pathological evidence suggest an association between Parkinson's disease (PD) and peripheral neuropathy (PNP), with a possible causative role of levodopa metabolic products, such as homocysteine and methylmalonic acid. METHODS: We conducted a systematic review of studies reporting cases of PNP in l-dopa-treated PD patients indexed in PubMed between January 1990 and March 2018. RESULTS: We identified 38 articles reporting cases of PNP in PD patients treated with oral l-dopa or with l-dopa/carbidopa intestinal gel infusion (LCIG). Prevalence of PNP was 30.2% in the former group and 42.1% in the latter. Oral l-dopa was mostly associated with slowly progressive PNP, whereas LCIG showed an acute or subacute onset in 35.7% of cases. In both groups, there was an association between PNP and higher l-dopa doses, as well as with the following biochemical alterations: increased homocysteine; reduced vitamin B12; increased methylmalonic acid; and reduced vitamin B6. A skin biopsy was performed in 181 patients, showing signs of small fibers neuropathy in 169 (93.4%). Positive, yet preliminary, results were observed in patients receiving periodic vitamin supplementation. CONCLUSIONS: Over one third of PD patients in treatment with l-dopa may develop PNP, with a significantly higher prevalence of acute and subacute forms in those receiving LCIG. Pathogenic mechanisms remain unclear, but possibly related to a complex interplay between peripheral neurodegenerative processes and l-dopa neurotoxic metabolites. Prospective, randomized, clinical trials are required to identify factors associated with the onset and progression of PD-associated PNP and clarify the protective role of B-group vitamin supplementation.

Peripheral neuropathies and aging.

Neuropathies are very common in the population over 65 years old and their prevalence increases with age. The prevalence of polyneuropathies is about 7% in the elderly. However, other possible neuropathies should not be overlooked. Diabetes mellitus is the first cause of neuropathy in the world. Beyond 80 years-old, the risk of finding no etiology is about 40% but it implies a minimum initial explorations. A vitamin deficiency, a dysimmune or even hereditary cause should be eliminated in the elderly subject, keeping in mind the characteristics of age. We propose a review of the different forms of neuropathies by emphasizing the clinical or electrophysiological particularities of the elderly.

Ion channels and neuropathic pain.

Pain behaviors in a Fabry mouse model are associated with the accumulation of a fat molecule that disrupts sodium ion channels in small fiber neurons.

Functional Evaluation of Small Fiber Pathways in Primary Restless Legs Syndrome: Aδ Pathway Study.

STUDY OBJECTIVES: The aim of this study was to provide a neurophysiological evaluation of the function of large and small fibers, particularly the peripheral part of the thermonociceptive Aδ pathway in patients with primary restless legs syndrome (RLS). METHODS: The main evaluation was based on an analysis of the parameters of laser-evoked potentials (LEPs), N2 and P2 components, and an assessment of thermonociceptive thresholds (pain thresholds; PThs). Routine nerve conduction studies (NCS) were also performed. RESULTS: No essential or important differences of clinical significance were observed in the parameters of large fiber conduction between the study and the control groups. Prolonged latencies of N2 and P2 potentials were obtained during foot stimulation in patients with primary RLS when compared to controls (N2, P2-lower right limb, and N2-lower left limb). We also observed higher amplitudes of LEPs evaluated as P2 and N2-P2 potentials in patients with primary RLS in comparison with the control group. Significantly higher (normal distribution P < .05) thermonociceptive thresholds in both lower and upper limbs were found in the RLS group. CONCLUSIONS: On the basis of the analysis of LEPs and their comparison with the respective results from the control group, the presence of functional disability of the thermonociceptive Aδ pathway was confirmed in patients with primary RLS. The results indicated the presence of changes in the conduction of small fiber pathways in the pathomechanism of idiopathic RLS.

Reproducibility of axon reflex-related vasodilation assessed by dynamic thermal imaging in healthy subjects.

INTRODUCTION: Small nerve fiber dysfunction is an early feature of diabetic neuropathy. There is a strong clinical need for a non-invasive method to assess small nerve fiber function. Small nerve fibers mediate axon reflex-related vasodilation and play an important role in thermoregulation. Assessing the reflex vasodilation after local heating might elucidate some aspects of small fiber functioning. In this study, we determined the reproducibility of the reflex vasodilation after short local heating in healthy subjects, assessed with thermal imaging and laser Doppler imaging. METHODS: Healthy subjects underwent six heating rounds in one session (protocol I, N=10) or spread over two visits (protocol II, N=20). Reflex vasodilation was elicited by heating the skin to 42°C with an infrared lamp. Skin temperature and skin blood flow were recorded during heating and recovery with a thermal imaging camera and a laser Doppler imager. Skin temperature curves were fitted with a mathematical model to describe the heating and recovery phase with time constant tau (tauHeat and tauCool1). RESULTS: The reproducibility of tau within a session was moderate to excellent (intra-class correlation coefficient 0.42-0.86) and good (0.71-0.72) between different sessions. Within one session the differences in tauHeat were small (bias±SD -1.3±18.9s); the bias between two visits was -1.2±12.2s. For tauCool1 the differences were also small, 1.4±6.6s within a session and between visits -1.4±11.6s. CONCLUSIONS: The heat induced axon reflex-related vasodilation, assessed with thermal imaging and laser Doppler imaging, was reproducible both within a session and between different sessions. Tau describes the temporal profile in one parameter and represents the effects of all changes including blood flow and as such, is an indicator of the vasodilator function. TauHeat and tauCool1 can accurately describe the dynamics of the axon reflex-related vasodilator response in the heating and recovery phase respectively.

Characterization of Pain in Familial Amyloid Polyneuropathy.

UNLABELLED: Familial amyloid polyneuropathy (FAP) caused by transthyretin (TTR) mutation is a small-fiber predominant polyneuropathy, exposing patients with TTR-FAP to development of neuropathic pain. However, the painful nature of TTR-FAP has never been specifically addressed. In this study, we compared 2 groups of 16 patients with either painless or painful TTR-FAP with regard to various clinical and neurophysiologic variables, including laser evoked potential (LEP) recording and quantitative sensory testing. The 2 groups of patients did not differ on any clinical or neurophysiologic variable. Patients with painful TTR-FAP complained of ongoing burning pain sensations, pain aggravation at rest, paroxysmal pain (electric shock and stabbing sensations), or provoked pain (mostly dynamic mechanical allodynia). However, the symptomatic presentation of painful TTR-FAP evolved with the course of the disease. The duration of the disease and the severity of small-fiber lesions (increase in thermal thresholds and reduction in LEP amplitude) correlated negatively with the intensity of ongoing burning sensations and positively with the intensity of paroxysmal pain. In addition, small-fiber preservation correlated positively with cold allodynia and pain aggravation at rest and negatively with dynamic mechanical allodynia. Peripheral sensitization of small-diameter nociceptive axons might occur in early TTR-FAP and be responsible for the burning sensation and cold allodynia. As polyneuropathy and small-fiber loss progress, paroxysmal pain and dynamic mechanical allodynia may develop as a result of central sensitization generated by abnormal activities affecting relatively spared large-diameter sensory fibers. PERSPECTIVE: Pain in TTR-FAP includes several mechanisms varying with the course of the disease and the involvement of the different types of nerve fibers.

Corneal confocal microscopy: Recent progress in the evaluation of diabetic neuropathy.

The present brief review discusses recent progress with corneal confocal microscopy for the evaluation of diabetic sensorimotor polyneuropathy. Corneal confocal microscopy is a new, non-invasive and reproducible diagnostic modality, and it can also be easily applied for patient follow up. It enables new perspectives of studying the natural history of diabetic sensorimotor polyneuropathy, severity of nerve fiber pathology and documenting early nerve fiber regeneration after therapeutic intervention. It shows moderate to high sensitivity and specificity for the timely diagnosis of diabetic sensorimotor polyneuropathy. Currently, corneal confocal microscopy is mainly used in specialized centers, but deserves more widespread application for the assessment of diabetic sensorimotor polyneuropathy. Finally, further progress is required in terms of technical improvements for automated nerve fiber quantification and for analysis of larger images.

Matters of fiber size and myonuclear domain: Does size matter more than age?

INTRODUCTION: The relationship between fiber size and myonuclear content is poorly understood. METHODS: Biopsy cross-sections from young and old trained and untrained healthy individuals were analyzed for fiber area and myonuclei, and 2 fiber-size-dependent cluster analyses were performed. RESULTS: When comparing fibers of similar size, no effect of training or age was found for myonuclear domain. There was a linear relationship between fiber area and myonuclei per fiber (r = 0.99; P < 0.001) and a non-linear relationship between fiber area and domain (r = 0.97-0.99; P < 0.0001), with a markedly smaller domain in fibers <3,000 µm(2). A higher proportion of type II fibers <3,000 µm(2) was observed in the old subjects. CONCLUSIONS: These findings suggest that age-related reductions in myonuclear domain size could be explained by the greater proportion of small fibers. The data also highlight the usefulness of determining fiber-size-based clusters for gaining mechanistic insight into the relationship between skeletal muscle fiber size and myonuclear content.

Small-nerve-fiber pathology in critical illness documented by serial skin biopsies.

INTRODUCTION: Small-fiber pathology can develop in the acute phase of critical illness and may explain chronic sensory impairment and pain in critical care survivors. METHODS: Eleven adult ischemic stroke patients in a neurocritical care unit were enrolled in an observational cohort study. Intraepidermal nerve fiber density (IENFD) in the distal leg was assessed on admission to the intensive care unit and 10-14 days later, together with electrophysiological testing. RESULTS: Of the 11 patients recruited, 9 (82%) had sepsis or multiple-organ failure. Median IENFD on admission (5.05 fibers/mm) decreased significantly to 2.18 fibers/mm (P < 0.001), and abnormal IENFD was found in 6 patients (54.5%). Electrodiagnostic signs of large-fiber neuropathy and/or myopathy were found in 6 patients (54.5%), and autonomic dysfunction was found in 2 patients (18.2%). CONCLUSION: Serial IENFD measurements confirmed the development of small-fiber sensory involvement in the acute phase of critical illness.

Clinical and diagnostic features of small fiber damage in diabetic polyneuropathy.

Small fiber neuropathy represents a significant component of diabetic sensorimotor polyneuropathy (DSPN) which has to date been ignored in most recommendations for the diagnosis of DSPN. Small fibers predominate in the peripheral nerve, serve crucial and highly clinically relevant functions such as pain, and regulate microvascular blood flow, mediating the mechanisms underlying foot ulceration. An increasing number of diagnostic tests have been developed to quantify small fiber damage. Because small fiber damage precedes large fiber damage, diagnostic tests for DSPN show good sensitivity but moderate specificity, because the gold standard which is used to define DSPN is large fiber-weighted. Hence new diagnostic algorithms for DSPN should acknowledge this emerging data and incorporate small fiber evaluation as a key measure in the diagnosis of DSPN, especially early neuropathy.

Postural tachycardia syndrome following human papillomavirus vaccination.

BACKGROUND AND PURPOSE: Postural tachycardia syndrome (POTS) is a heterogeneous disorder of the autonomic nervous system that may have an autoimmune etiology. METHODS: Six patients who developed new onset POTS 6 days to 2 months following human papillomavirus vaccination are reported. RESULTS: Three patients also had neurocardiogenic syncope, and three patients were diagnosed with possible small fiber neuropathy. Symptoms in all patients improved over 3 years with pharmacotherapy and non-pharmacological measures but residual symptoms persisted. Molecular mimicry with formation of cross-reacting autoantibodies to the potential targets of the autonomic ganglia, neurons, cardiac proteins or vascular receptors is considered as a possible pathogenesis of new onset POTS after immunization. CONCLUSION: Correct diagnosis of POTS and awareness that POTS may occur after vaccination in young women is essential for prompt and effective management of this condition.

Plantar thermography is useful in the early diagnosis of diabetic neuropathy

OBJECTIVES: This study evaluated plantar thermography sensitivity and specificity in diagnosing diabetic polyneuropathy using cardiac tests (heart rate variability) as a reference standard because autonomic small fibers are affected first by this disease. METHODS: Seventy-nine individuals between the ages of 19 and 79 years old (28 males) were evaluated and divided into three groups: control (n = 37), pre-diabetics (n = 13) and type 2 diabetics (n = 29). The plantar images were recorded at baseline and then minutes after a provocative maneuver (Cold Stress Test) using an infrared camera that is appropriate for clinical use. Two thermographic variables were studied: the thermal recovery index and the interdigital anisothermal technique. Heart rate variability was measured in a seven-test battery that included three spectral indexes (in the frequency domain) and four Ewing tests (the Valsalva maneuver, the orthostatic test, a deep breathing test, and the orthostatic hypotension test). Other classically recommended tests were applied, including electromyography (EMG), Michigan inventory, and a clinical interview that included a neurological physical examination. RESULTS: Among the diabetic patients, the interdigital anisothermal technique alone performed better than the thermal recovery index alone, with a better sensitivity (81.3%) and specificity (46.2%). For the pre-diabetic patients, the three tests performed equally well. None of the control subjects displayed abnormal interdigital anisothermal readouts or thermal recovery indices, which precluded the sensitivity estimation in this sample of subjects. However, the specificity (70.6%) was higher in this group. CONCLUSION: In this study, plantar thermography, which predominately considers the small and autonomic fibers that are commonly associated with a sub-clinical condition, proved useful in diagnosing diabetic neuropathy early. The interdigital anisothermal test, when used alone, performed best.