The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Rayaz A Malik - One of the best experts on this subject based on the ideXlab platform.
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early corneal nerve Fibre damage and increased langerhans cell Density in children with type 1 diabetes mellitus
Scientific Reports, 2019Co-Authors: Maryam Ferdousi, Rayaz A Malik, Kenneth Romanchuk, Heidi Virtanen, Christine Millar, Daniele PacaudAbstract:Corneal confocal microscopy (CCM) has been used to identify corneal nerve damage and increased Langerhans cell (LC) Density in adults with Type 1 diabetes mellitus (T1DM). The purpose of this study was to evaluate whether corneal confocal microscopy can identify early corneal nerve damage and change in LC Density in children and adolescents with T1DM. 64 participants with T1DM (age-14.6 ± 2.5 years, duration of diabetes-9.1 ± 2.7 years, HbA1c-75.66 ± 2.53 mmol/mol [9.1 ± 1.8%]) and 48 age-matched healthy control subjects underwent CCM. Sub-basal corneal nerve morphology and the Density of mature and immature LCs was quantified. Corneal nerve Fibre length and branch Density were lower, whilst Fibre Density and tortuosity did not differ and both immature and mature LC Density was significantly higher in T1DM compared to control subjects. There was no association between HbA1c and duration of diabetes with nerve Fibre parameters or LC’s Density. Children and adolescents with T1DM demonstrate early immune activation and nerve degeneration.
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corneal nerve Fibre damage precedes diabetic retinopathy in patients with type 2 diabetes mellitus
Diabetic Medicine, 2014Co-Authors: Gulfidan Bitirgen, Rayaz A Malik, Ahmet Ozkagnici, Hurkan KerimogluAbstract:Aims To quantify the morphological alterations in corneal nerve Fibres and cells in patients with Type 2 diabetes mellitus in relation to the severity of diabetic retinopathy. Methods One hundred and thirty-two eyes of 132 patients with Type 2 diabetes and 32 eyes of 32 healthy control subjects were evaluated with in vivo corneal confocal microscopy. Patients with diabetes were classified into three groups: patients without diabetic retinopathy, patients with non-proliferative diabetic retinopathy and patients with proliferative diabetic retinopathy. Anterior and posterior stromal keratocyte, endothelial cell and basal epithelial cell densities and sub-basal nerve Fibre structure were evaluated. Results Significant reductions in basal epithelial cell, anterior stromal keratocyte and endothelial cell densities were observed only in patients with diabetic retinopathy. However, nerve Fibre Density, nerve branch Density and nerve Fibre length were reduced in patients without diabetic retinopathy and worsened progressively with increasing severity of retinopathy. Conclusions Corneal cell pathology occurs in patients with diabetic retinopathy, but corneal nerve Fibre damage seems to precede the development of diabetic retinopathy.
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small Fibre neuropathy role in the diagnosis of diabetic sensorimotor polyneuropathy
Diabetes-metabolism Research and Reviews, 2011Co-Authors: Rayaz A Malik, Aristidis Veves, Solomon Tesfaye, Gordon Smith, Norman E Cameron, Douglas W Zochodne, Giuseppe LauriaAbstract:Small Fibres constitute 70-90% of peripheral nerve Fibres and regulate several key functions such as tissue blood flow, temperature and pain perception as well as sweating, all of which are highly relevant to the clinical presentation and adverse outcomes associated with foot ulcerations in patients with diabetes. Recent studies demonstrated significant abnormalities in the small Fibres in subjects with impaired glucose tolerance and diabetes, despite normal electrophysiology, suggesting that the earliest nerve Fibre damage is to the small Fibres. Unfortunately, guidelines and consensus statements focus on large Fibres and continue to advocate electrophysiology as a diagnostic modality and as a primary end point for the assessment of therapeutic benefit. (In part, this reflects the difficulties in quantifying small Fibre dysfunction and damage.) We have therefore critically assessed currently available techniques that measure small Fibre dysfunction in diabetic neuropathy, using quantitative sensory and sudomotor testing. We have assessed the role of identifying structural damage by quantifying intraepidermal nerve Fibre Density in skin biopsies and corneal nerve morphology using corneal confocal microscopy. Finally, we propose a definition for diabetic neuropathy that incorporates small Fibre damage.
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corneal confocal microscopy a novel means to detect nerve Fibre damage in idiopathic small Fibre neuropathy
Experimental Neurology, 2010Co-Authors: Mitra Tavakoli, Hassan Fadavi, Andrew Marshall, Andrew Jm Boulton, Nathan Efron, Robert D S Pitceathly, David W Gow, Mark E Roberts, Rayaz A MalikAbstract:Patients with idiopathic small Fibre neuropathy (ISFN) have been shown to have significant intraepidermal nerve Fibre loss and an increased prevalence of impaired glucose tolerance (IGT). It has been suggested that the dysglycemia of IGT and additional metabolic risk factors may contribute to small nerve Fibre damage in these patients. Twenty-five patients with ISFN and 12 aged-matched control subjects underwent a detailed evaluation of neuropathic symptoms, neurological deficits (Neuropathy deficit score (NDS); Nerve Conduction Studies (NCS); Quantitative Sensory Testing (QST) and Corneal Confocal Microscopy (CCM)) to quantify small nerve Fibre pathology. Eight (32%) patients had IGT. Whilst all patients with ISFN had significant neuropathic symptoms, NDS, NCS and QST except for warm thresholds were normal. Corneal sensitivity was reduced and CCM demonstrated a significant reduction in corneal nerve Fibre Density (NFD) (P<0.0001), nerve branch Density (NBD) (P<0.0001), nerve Fibre length (NFL) (P<0.0001) and an increase in nerve Fibre tortuosity (NFT) (P<0.0001). However these parameters did not differ between ISFN patients with and without IGT, nor did they correlate with BMI, lipids and blood pressure. Corneal confocal microscopy provides a sensitive non-invasive means to detect small nerve Fibre damage in patients with ISFN and metabolic abnormalities do not relate to nerve damage.
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biopsy of the posterior interosseous nerve a low morbidity method for assessment of peripheral nerve disorders
Diabetic Medicine, 2009Co-Authors: Niels O B Thomsen, Moaz A Mojaddidi, Rayaz A Malik, Lars DahlinAbstract:AIMS: The sural nerve is the commonest peripheral nerve biopsied to help in the diagnosis of peripheral neuropathy of unknown cause. However, associated complications limit its use. The aim was, as an alternative, to asses biopsy of the terminal branch of the posterior interosseous nerve (PIN) in the forearm. METHODS: PIN pathology was morphometrically quantified in 10 male patients with Type 2 diabetes and compared with six PIN biopsy specimens taken post mortem from male cadavers with no history of neuropathy or trauma. RESULTS: The PIN biopsy procedure provides a long (approximately 3 cm) mono- or bifascicular nerve biopsy with generous epineurial tissue and adjacent vessels. Our results show a significantly lower myelinated Fibre Density in subjects with diabetes [5782 (3332-9060)/mm(2)] compared with autopsy control material [9256 (6593-12,935)/mm(2), P < 0.007]. No postoperative discomfort or complications were encountered. CONCLUSIONS: A reduction in myelinated Fibre Density has previously been shown to be a clinically meaningful measure of neuropathy in diabetic patients. We demonstrate similar findings using the PIN biopsy. The PIN biopsy procedure fulfils the criteria for nerve biopsy and was well tolerated by the patients. It may be a possible alternative to sural nerve biopsy to allow for diagnosis of neuropathy. (Less)
Einar Wildersmith - One of the best experts on this subject based on the ideXlab platform.
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stimulated skin wrinkling for predicting intraepidermal nerve Fibre Density
Clinical Neurophysiology, 2009Co-Authors: Einar Wildersmith, Yaling Guo, Adeline ChowAbstract:Abstract Objective To determine the usefulness of stimulated skin wrinkling using EMLA and water immersion in detecting abnormal intraepidermal nerve Fibre Density. Methods In a prospective study of patients with predominantly sensory polyneuropathy, we tested sensitivity and specificity of stimulated skin wrinkling using EMLA and water immersion in detecting abnormal intraepidermal nerve Fibre Density (IENFD). Results EMLA stimulated wrinkling showed a sensitivity of 81.6% and specificity of 74.7% in detecting abnormal IENFD and water wrinkling a sensitivity of 71.4% and specificity of 73%. The positive and negative predictive values for detecting abnormal IENFD were 88.3% and 63.3% for EMLA wrinkling, for water wrinkling 83.3% and 57.4%. Intra-observer EMLA score variability was good with no change in assignment of wrinkling and inter-observer score variability resulted in 1–5 changes in wrinkling score which translated into a change of the wrinkling status from normal to abnormal on two occasions. Conclusions Stimulated skin wrinkling correlates well with abnormal intraepidermal nerve Fibre Density. Significance Our study suggests that EMLA induced stimulated skin wrinkling is a useful alternative parameter for predicting abnormal intraepidermal nerve Fibre Density.
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skin wrinkling for diagnosing small Fibre neuropathy comparison with epidermal nerve Density and sympathetic skin response
Journal of Neurology Neurosurgery and Psychiatry, 2008Co-Authors: Hock Luen Teoh, Adeline Chow, Einar WildersmithAbstract:Objective: To compare simple tests of small nerve Fibre function with intraepidermal nerve Fibre Density (IENFD) in the evaluation of small Fibre neuropathy (SFN). Methods: Patients with idiopathic SFN of the hands were prospectively studied. Evaluation involved clinical examination, nerve conduction studies, sympathetic skin response (SSR) and skin wrinkling stimulated by water and EMLA (eutectic mixture of local anaesthetics). Results: Of 21 patients, 16 (76%) had low IENFD, 15 (71%) impaired water-induced wrinkling, 14 (67%) impaired EMLA-induced wrinkling, and nine (43%) abnormal SSR. Conclusions: Stimulated skin wrinkling was nearly as sensitive as IENFD in diagnosing SFN, whereas SSR was of less use. Stimulated skin wrinkling is a useful supportive test when IENFD or other tests of small nerve Fibre function are not available.
David Andrew - One of the best experts on this subject based on the ideXlab platform.
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temporal mismatch between pain behaviour skin nerve growth factor and intra epidermal nerve Fibre Density in trigeminal neuropathic pain
BMC Neuroscience, 2014Co-Authors: Laura J Evans, Alison R Loescher, Fiona M Boissonade, Simon A Whawell, P P Robinson, David AndrewAbstract:The neurotrophin Nerve Growth factor (NGF) is known to influence the phenotype of mature nociceptors, for example by altering synthesis of neuropeptides, and changes in NGF levels have been implicated in the pathophysiology of chronic pain conditions such as neuropathic pain. We have tested the hypothesis that after partial nerve injury, NGF accumulates within the skin and causes ‘pro-nociceptive’ phenotypic changes in the remaining population of sensory nerve Fibres, which could underpin the development of neuropathic pain. Eleven days after chronic constriction injury of the rat mental nerve the intra-epidermal nerve Fibre Density of the chin skin from had reduced from 11.6 ± 4.9 Fibres/mm to 1.0 ± 0.4 Fibres/mm; this slowly recovered to 2.4 ± 2.0 Fibres/mm on day 14 and 4.0 ± 0.8 Fibres/mm on day 21. Cold hyperalgesia in the ipsilateral lower lip was detectable 11 days after chronic constriction injury, although at this time skin [NGF] did not differ between sides. At 14 days post-injury, there was a significantly greater [NGF] ipsilaterally compared to contralaterally (ipsilateral = 111 ± 23 pg/mg, contralateral = 69 ± 13 pg/mg), but there was no behavioural evidence of neuropathic pain at this time-point. By 21 days post-injury, skin [NGF] was elevated bilaterally and there was a significant increase in the proportion of TrkA-positive (the high-affinity NGF receptor) intra-epidermal nerve Fibres that were immunolabelled for the neuropeptide Calcitonin Gene-related peptide. The temporal mismatch in behaviour, skin [NGF] and phenotypic changes in sensory nerve Fibres indicate that increased [NGF] does not cause hyperalgesia after partial mental nerve injury, although it may contribute to the altered neurochemistry of cutaneous nerve Fibres.
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temporal mismatch between pain behaviour skin nerve growth factor and intra epidermal nerve Fibre Density in trigeminal neuropathic pain
BMC Neuroscience, 2014Co-Authors: Laura J Evans, Alison R Loescher, Fiona M Boissonade, Simon A Whawell, P P Robinson, David AndrewAbstract:Background The neurotrophin Nerve Growth factor (NGF) is known to influence the phenotype of mature nociceptors, for example by altering synthesis of neuropeptides, and changes in NGF levels have been implicated in the pathophysiology of chronic pain conditions such as neuropathic pain. We have tested the hypothesis that after partial nerve injury, NGF accumulates within the skin and causes ‘pro-nociceptive’ phenotypic changes in the remaining population of sensory nerve Fibres, which could underpin the development of neuropathic pain.
Charles L Rice - One of the best experts on this subject based on the ideXlab platform.
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increased neuromuscular transmission instability and motor unit remodelling with diabetic neuropathy as assessed using novel near Fibre motor unit potential parameters
Clinical Neurophysiology, 2015Co-Authors: Matti D Allen, Daniel W Stashuk, Maddison L Hourigan, Timothy J Doherty, Kurt Kimpinski, Charles L RiceAbstract:Abstract Objective To assess the degree of neuromuscular transmission variability and motor unit (MU) remodelling in patients with diabetic polyneuropathy (DPN) using decomposition-based quantitative electromyography (DQEMG) and near Fibre (NF) motor unit potential (MUP) parameters. Methods The tibialis anterior (TA) muscle was tested in 12 patients with DPN (65±15years) and 12 controls (63±15years). DQEMG was used to analyze electromyographic (EMG) signals collected during voluntary contractions. MUP and NF MUP parameters were analyzed. NF MUPs were obtained by high-pass filtering MUP template waveforms, which isolates contributions of Fibres that are close to the needle detection surface. NF MUP parameters provided assessment of motor unit size (NF area), Fibre Density (NF Fibre count) and contribution dispersion (NF dispersion) and neuromuscular transmission instability (NF jiggle). Results DPN patients had larger (+45% NF area), more complex (+30% NF Fibre count), and less stable (+30% NF jiggle) NF MUPs ( p r =0.63; p r =0.46; p Conclusions DPN is associated with neuromuscular transmission instability and MU remodelling that can be assessed using DQEMG. Significance DQEMG-derived NF MUP parameters may be useful in identifying patients in early stages of neuromuscular dysfunction related to DPN.
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increased neuromuscular transmission instability and motor unit remodelling with diabetic neuropathy as assessed using novel near Fibre motor unit potential parameters
Clinical Neurophysiology, 2015Co-Authors: Matti D Allen, Daniel W Stashuk, Maddison L Hourigan, Timothy J Doherty, Kurt Kimpinski, Charles L RiceAbstract:Abstract Objective To assess the degree of neuromuscular transmission variability and motor unit (MU) remodelling in patients with diabetic polyneuropathy (DPN) using decomposition-based quantitative electromyography (DQEMG) and near Fibre (NF) motor unit potential (MUP) parameters. Methods The tibialis anterior (TA) muscle was tested in 12 patients with DPN (65±15years) and 12 controls (63±15years). DQEMG was used to analyze electromyographic (EMG) signals collected during voluntary contractions. MUP and NF MUP parameters were analyzed. NF MUPs were obtained by high-pass filtering MUP template waveforms, which isolates contributions of Fibres that are close to the needle detection surface. NF MUP parameters provided assessment of motor unit size (NF area), Fibre Density (NF Fibre count) and contribution dispersion (NF dispersion) and neuromuscular transmission instability (NF jiggle). Results DPN patients had larger (+45% NF area), more complex (+30% NF Fibre count), and less stable (+30% NF jiggle) NF MUPs ( p r =0.63; p r =0.46; p Conclusions DPN is associated with neuromuscular transmission instability and MU remodelling that can be assessed using DQEMG. Significance DQEMG-derived NF MUP parameters may be useful in identifying patients in early stages of neuromuscular dysfunction related to DPN.
Adeline Chow - One of the best experts on this subject based on the ideXlab platform.
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stimulated skin wrinkling for predicting intraepidermal nerve Fibre Density
Clinical Neurophysiology, 2009Co-Authors: Einar Wildersmith, Yaling Guo, Adeline ChowAbstract:Abstract Objective To determine the usefulness of stimulated skin wrinkling using EMLA and water immersion in detecting abnormal intraepidermal nerve Fibre Density. Methods In a prospective study of patients with predominantly sensory polyneuropathy, we tested sensitivity and specificity of stimulated skin wrinkling using EMLA and water immersion in detecting abnormal intraepidermal nerve Fibre Density (IENFD). Results EMLA stimulated wrinkling showed a sensitivity of 81.6% and specificity of 74.7% in detecting abnormal IENFD and water wrinkling a sensitivity of 71.4% and specificity of 73%. The positive and negative predictive values for detecting abnormal IENFD were 88.3% and 63.3% for EMLA wrinkling, for water wrinkling 83.3% and 57.4%. Intra-observer EMLA score variability was good with no change in assignment of wrinkling and inter-observer score variability resulted in 1–5 changes in wrinkling score which translated into a change of the wrinkling status from normal to abnormal on two occasions. Conclusions Stimulated skin wrinkling correlates well with abnormal intraepidermal nerve Fibre Density. Significance Our study suggests that EMLA induced stimulated skin wrinkling is a useful alternative parameter for predicting abnormal intraepidermal nerve Fibre Density.
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skin wrinkling for diagnosing small Fibre neuropathy comparison with epidermal nerve Density and sympathetic skin response
Journal of Neurology Neurosurgery and Psychiatry, 2008Co-Authors: Hock Luen Teoh, Adeline Chow, Einar WildersmithAbstract:Objective: To compare simple tests of small nerve Fibre function with intraepidermal nerve Fibre Density (IENFD) in the evaluation of small Fibre neuropathy (SFN). Methods: Patients with idiopathic SFN of the hands were prospectively studied. Evaluation involved clinical examination, nerve conduction studies, sympathetic skin response (SSR) and skin wrinkling stimulated by water and EMLA (eutectic mixture of local anaesthetics). Results: Of 21 patients, 16 (76%) had low IENFD, 15 (71%) impaired water-induced wrinkling, 14 (67%) impaired EMLA-induced wrinkling, and nine (43%) abnormal SSR. Conclusions: Stimulated skin wrinkling was nearly as sensitive as IENFD in diagnosing SFN, whereas SSR was of less use. Stimulated skin wrinkling is a useful supportive test when IENFD or other tests of small nerve Fibre function are not available.