The Experts below are selected from a list of 2109 Experts worldwide ranked by ideXlab platform
Matthew C. Kiernan - One of the best experts on this subject based on the ideXlab platform.
-
Changes in long term peripheral nerve biophysical properties in childhood cancer survivors following neurotoxic chemotherapy
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology, 2020Co-Authors: Tejaswi Kandula, Matthew C. Kiernan, Arun V. Krishnan, Michelle A. Farrar, Kate A. Carey, Richard J. Cohn, Karen Johnston, Susanna B. ParkAbstract:Abstract Objective In the context of increasing numbers of childhood cancer survivors (CCS), this study aimed to enhance understanding of the biophysical basis for long term chemotherapy induced peripheral neuropathy from different chemotherapy agents in CCS. Methods Detailed cross-sectional neurophysiological examination, using median nerve Axonal Excitability studies, alongside clinical assessments, in 103 long term CCS (10.5 ± 0.6 years post-treatment). Results Cisplatin treated CCS (n = 16) demonstrated multiple sensory Axonal Excitability changes including increased threshold (P Conclusion Persistent long term changes in Axonal biophysical properties vary with different chemotherapy agents, most evident after cisplatin exposure. Longitudinal studies of nerve function during chemotherapy treatment are required to further evaluate these differences and their mechanistic basis. Significance This study provides a unique biophysical perspective for persistent cisplatin related neurotoxicity in children, previously under recognised.
-
Measurement of Axonal Excitability: Consensus guidelines.
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology, 2019Co-Authors: Matthew C. Kiernan, Satoshi Kuwabara, Sonoko Misawa, Christian Krarup, Arun V. Krishnan, Susanna B. Park, Hugh Bostock, Ryuji Kaji, Cindy Shin Yi Lin, Mihai MoldovanAbstract:Abstract Measurement of Axonal Excitability provides an in vivo indication of the properties of the nerve membrane and of the ion channels expressed on these axons. Axonal Excitability techniques have been utilised to investigate the pathophysiological mechanisms underlying neurological diseases. This document presents guidelines derived for such studies, based on a consensus of international experts, and highlights the potential difficulties when interpreting abnormalities in diseased axons. The present manuscript provides a state-of-the-art review of the findings of Axonal Excitability studies and their interpretation, in addition to suggesting guidelines for the optimal performance of Excitability studies.
-
009 Axonal Excitability properties in dravet’s syndrome reflect effect of loss of sodium channels
Journal of Neurology Neurosurgery & Psychiatry, 2019Co-Authors: Michelle A. Farrar, James Howells, Cindy S.-y. Lin, Matthew C. Kiernan, Susan E. Tomlinson, Kate A. Carey, Susanna B. Park, Georgina Hollingsworth, John A. Lawson, Samuel F. BerkovicAbstract:Introduction Mutations in SCN1A encoding the Nav1.1 subunit of the neuronal sodium channel underlie the devastating epilepsy of Dravet’s syndrome.1 The mechanism by which Nav1.1 dysfunction causes seizures is not clear. In vitro and in silico channel evaluation can support mutation pathogenicity but cannot define the in vivo impact of channel dysfunction. Axonal Excitability studies can show the pattern of single-channel dysfunction in disorders where the channel is peripherally expressed.2 This study was undertaken to determine whether Axonal Excitability studies could detect changes in Dravet’s patients related to the condition or due to medication effect. Methods Patients with Dravet’s syndrome were recruited from clinics in Sydney and Melbourne and Axonal Excitability studies were performed. Excitability results were analysed in 3 age groups and compared to age-matched normal controls. Results Twenty six patients (ages 2–46) were studied. Findings were most pronounced in patients aged 20–46 (n=7) with 6.9% greater increase in threshold during hyperpolarization(p=0.1), 7.6% greater threshold decrease on depolarization(p=0.005) and, in the recovery cycle, 19.7% reduction in superExcitability(p=0.002) and 26% reduction in subExcitability(p=0.03). Axonal Excitability studies resembled previously published changes seen in patients with sodium channel blockade caused by acute tetrodotoxin poisoning.3 Conclusions Changes in Excitability of Axonal membrane in Dravet’s syndrome are consistent with a decrease in sodium channel function. As the affected channel in Dravet’s syndrome is not peripherally expressed, the effect seen is likely due to the heavy anticonvulsant regime required to control epilepsy, combined with a progressive loss of sodium channel function that occurs with age. References Meisler MH, O’Brien JE, Sharkey LM. Sodium channel gene family: epilepsy mutations, gene interactions and modifier effects. J Physiol 2010;588:1841–1848. Tomlinson SE, Howells J, Burke D. In vivo assessment of neurological channelopathies: Application of peripheral nerve Excitability studies. Neuropharmacology. 2018 Apr;132:98–107. Kiernan MC, Isbister GK, Lin CS, Burke D, Bostock H. Acute tetrodotoxin-induced neurotoxicity after ingestion of puffer fish. Ann Neurol 2005;57:339–48.
-
5. Neurophysiological dysfunction in chemotherapy-treated patients: Comparison of different platinum analogues
Clinical Neurophysiology, 2018Co-Authors: Hannah C. Timmins, Jenna Murray, Matthew C. Kiernan, David Goldstein, Peter Grimison, Keith Cox, Lisa G. Horvath, Craig R. Lewis, Susanna B. ParkAbstract:Objective Chemotherapy-induced peripheral neuropathy is a prominent side effect of treatment with platinum-based chemotherapies cisplatin and oxaliplatin. Progressive abnormalities in sensory Axonal Excitability have been linked to neuropathy severity in oxaliplatin-treated patients, but not examined in cisplatin-treated patients. Methods Sensory Axonal Excitability studies were undertaken in median nerve. Neuropathy was assessed via total neuropathy score reduced (TNSr). Results Clinical severity of neuropathy was greater (TNSr: 6.9 ± 1.2) in oxaliplatin-treated patients (N = 16, Age: 57.1 ± 3 years, cumulative dose: 801 ± 63.5 mg/m 2 , median 6 months post-completion IQR: 4–12.5) than in cisplatin-treated patients (TNSr: 3.2 ± 0.6, p . 01 , N = 17, Age: 48.5 ± 4.3 years, cumulative dose: 316.5 ± 19.3 mg/m 2 , median 7 months post-completion IQR: 3–30.5). Cisplatin and oxaliplatin-treated patients demonstrated deficits in sensory nerve function compared to controls, with increased threshold change in Excitability (TEh90-100 ms Cis: −128.7 ± 4.7%; Ox: −140.9 ± 5.9%; control: −116.6 ± 3.1%, p . 01 ) and reduced median sensory amplitudes (Cis: 24.4 ± 3.0 μ V; Ox: 15.7 ± 3.0 μ V; control: 43.9 ± 1.1 μ V, p . 01 ) with greater abnormalities in oxaliplatin-treated patients ( p . 01 ). TEh90-100 ms was correlated to median amplitude (r = .418, p . 05 ), with patients demonstrating greater Excitability abnormalities also demonstrating greater reduction in sensory amplitude. Conclusions Changes in Axonal Excitability parameters are consistent between platinum-based chemotherapies and linked to neuropathy severity. Significance Platinum analogues demonstrate similar pathophysiological mechanisms of nerve dysfunction. Axonal Excitability techniques may provide a marker of Axonal dysfunction across different platinum chemotherapies.
-
Axonal Excitability in Amyotrophic Lateral Sclerosis
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2016Co-Authors: Susanna B. Park, Matthew C. Kiernan, Steve VucicAbstract:Axonal Excitability testing provides in vivo assessment of Axonal ion channel function and membrane potential. Excitability techniques have provided insights into the pathophysiological mechanisms underlying the development of neurodegeneration and clinical features of amyotrophic lateral sclerosis (ALS) and related neuromuscular disorders. Specifically, abnormalities of Na+ and K+ conductances contribute to development of membrane hyperExcitability in ALS, thereby leading to symptom generation of muscle cramps and fasciculations, in addition to promoting a neurodegenerative cascade via Ca2+-mediated processes. Modulation of Axonal ion channel function in ALS has resulted in significant symptomatic improvement that has been accompanied by stabilization of Axonal Excitability parameters. Separately, Axonal ion channel dysfunction evolves with disease progression and correlates with survival, thereby serving as a potential therapeutic biomarker in ALS. The present review provides an overview of Axonal Excitability techniques and the physiological mechanisms underlying membrane Excitability, with a focus on the role of Axonal ion channel dysfunction in motor neuron disease and related neuromuscular diseases.
David Burke - One of the best experts on this subject based on the ideXlab platform.
-
increased hcn channel driven inward rectification in benign cramp fasciculation syndrome
Brain, 2015Co-Authors: Dirk Czesnik, Melanie Wagenknecht, Susanne Hanner, James Howells, David Burke, Francesco Negro, Dario Farina, Walter PaulusAbstract:Muscle cramps are a common complaint associated with sudden painful involuntary contractions of a muscle. The mechanisms responsible for muscle cramps are still not clear. Axonal Excitability and multi-unit electromyography studies were performed in 20 patients suffering from benign cramp fasciculation syndrome, not currently on medication. The measures of Axonal Excitability suggested greater inward rectification, indicative of an increase in Ih. Mathematical modelling suggested that the data were best explained by depolarization of the voltage dependence of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Parameters associated with polarization of resting membrane potential were not changed. These findings suggest that a role for HCN channels may become apparent during the rhythmic discharge associated with a voluntary contraction. Consistent with this view, patients had higher motor unit discharge rates than healthy controls during maximal voluntary effort.
-
increased hcn channel driven inward rectification in benign cramp fasciculation syndrome
Brain, 2015Co-Authors: Dirk Czesnik, Melanie Wagenknecht, Susanne Hanner, James Howells, David Burke, Francesco Negro, Dario Farina, Walter PaulusAbstract:Muscle cramps are a common complaint associated with sudden painful involuntary contractions of a muscle. The mechanisms responsible for muscle cramps are still not clear. Axonal Excitability and multi-unit electromyography studies were performed in 20 patients suffering from benign cramp fasciculation syndrome, not currently on medication. The measures of Axonal Excitability suggested greater inward rectification, indicative of an increase in I h. Mathematical modelling suggested that the data were best explained by depolarization of the voltage dependence of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Parameters associated with polarization of resting membrane potential were not changed. These findings suggest that a role for HCN channels may become apparent during the rhythmic discharge associated with a voluntary contraction. Consistent with this view, patients had higher motor unit discharge rates than healthy controls during maximal voluntary effort. * Abbreviations : BCFS : benign cramp fasciculation syndrome CMAP : compound muscle action potential HCN : hyperpolarization-activated, cyclic nucleotide-gated cation
-
Axonal Excitability in primary amyloidotic neuropathy
Muscle & nerve, 2015Co-Authors: Jessica Hafner, Roula Ghaoui, Luke Coyle, David BurkeAbstract:Introduction: Acquired and hereditary amyloidosis can cause peripheral neuropathy, but the mechanisms by which this occurs have not been established. Threshold tracking techniques allow in vivo assessment of the properties of the Axonal membrane and may shed light on pathogenetic mechanisms underlying neuropathic disorders. Methods: We studied 10 subjects with primary amyloidosis using conventional nerve conduction studies and quantitative sensory, autonomic, and Axonal Excitability testing of median motor and sensory fibers. Results: As expected, subjects with amyloidosis had evidence of small- and large-fiber neuropathy on conventional testing. There was no significant difference in Axonal Excitability between subjects and controls apart from the stimulus required to activate sensory fibers. Conclusions: Amyloid-related neuropathy does not produce a change in membrane potential as either a primary or secondary event. This suggests that ischemia and Axonal compression are unlikely mechanisms for the neuropathy. Muscle Nerve 51: 443–445, 2015
-
Axonal Excitability in X-linked dominant Charcot Marie Tooth disease.
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology, 2013Co-Authors: Christina Liang, James Howells, Marina L. Kennerson, Garth A. Nicholson, David BurkeAbstract:Abstract Objective We investigated peripheral nerve function in X-linked Charcot–Marie–Tooth disease type 1 (CMTX1), and considered the functional consequences of mutant connexin-32. Methods Twelve subjects (9 female, 3 male) were assessed clinically, by nerve conduction and Excitability studies. A model of myelinated axon was used to clarify the contributing changes. Results All subjects had abnormal nerve conduction. Excitability studies on median nerve axons showed greater threshold changes to hyperpolarising currents, with “fanning out” in threshold electrotonus, and modest changes in the recovery cycle. Modelling suggested shortening of internodal length, increase in nodal fast potassium currents, shift of the voltage activation hyperpolarisation-activated cyclic-nucleotide-gated channels, and Axonal hyperpolarisation. Plotting threshold versus extent of hyperpolarising threshold change in threshold electrotonus distinguished the CMTX1 patients from other chronic demyelinating neuropathies reported in the literature except hereditary neuropathy with pressure palsies (HNPP). Conclusions Some measures of Axonal Excitability are similar in CMTX1 and HNPP (though not the recovery cycle), but they differ from those in other chronic demyelinating neuropathies. The findings in CMTX1 are consistent with known pathology, but are not correlated to neuropathy severity. Significance The findings in CMTX1 could be largely the result of morphological alterations, rather than plasticity in channel expression or distribution.
-
Axonal Excitability during ischemia in MELAS.
Muscle & nerve, 2013Co-Authors: Kishore R. Kumar, Carolyn M. Sue, David BurkeAbstract:Introduction In mitochondrial disease, it is likely that energy substrate depletion leads to paralysis of ATPase-dependent pumps, resulting in membrane depolarization. Axonal depolarization has been demonstrated in a crisis, but not in the resting state. We, therefore, stressed axons using ischemia to see if this would reveal abnormal responses, as occurs in diabetes mellitus. Methods Excitability of median nerve axons at the wrist was studied in 13 patients with MELAS (6 with glucose intolerance) and 17 control subjects in response to ischemia due to inflation of a cuff around the arm for 10 min. Results There were no significant differences in preischemic measures of Axonal Excitability or in the intra- and postischemic responses. Conclusions Although depolarization has been noted to occur spontaneously during a crisis, we could not demonstrate a defect of Axonal ATP-dependent mechanisms. The mechanisms underlying Axonal Excitability and neuropathy in diabetes may not apply to MELAS. Muscle Nerve 47: 762–765, 2013
Cindy S.-y. Lin - One of the best experts on this subject based on the ideXlab platform.
-
009 Axonal Excitability properties in dravet’s syndrome reflect effect of loss of sodium channels
Journal of Neurology Neurosurgery & Psychiatry, 2019Co-Authors: Michelle A. Farrar, James Howells, Cindy S.-y. Lin, Matthew C. Kiernan, Susan E. Tomlinson, Kate A. Carey, Susanna B. Park, Georgina Hollingsworth, John A. Lawson, Samuel F. BerkovicAbstract:Introduction Mutations in SCN1A encoding the Nav1.1 subunit of the neuronal sodium channel underlie the devastating epilepsy of Dravet’s syndrome.1 The mechanism by which Nav1.1 dysfunction causes seizures is not clear. In vitro and in silico channel evaluation can support mutation pathogenicity but cannot define the in vivo impact of channel dysfunction. Axonal Excitability studies can show the pattern of single-channel dysfunction in disorders where the channel is peripherally expressed.2 This study was undertaken to determine whether Axonal Excitability studies could detect changes in Dravet’s patients related to the condition or due to medication effect. Methods Patients with Dravet’s syndrome were recruited from clinics in Sydney and Melbourne and Axonal Excitability studies were performed. Excitability results were analysed in 3 age groups and compared to age-matched normal controls. Results Twenty six patients (ages 2–46) were studied. Findings were most pronounced in patients aged 20–46 (n=7) with 6.9% greater increase in threshold during hyperpolarization(p=0.1), 7.6% greater threshold decrease on depolarization(p=0.005) and, in the recovery cycle, 19.7% reduction in superExcitability(p=0.002) and 26% reduction in subExcitability(p=0.03). Axonal Excitability studies resembled previously published changes seen in patients with sodium channel blockade caused by acute tetrodotoxin poisoning.3 Conclusions Changes in Excitability of Axonal membrane in Dravet’s syndrome are consistent with a decrease in sodium channel function. As the affected channel in Dravet’s syndrome is not peripherally expressed, the effect seen is likely due to the heavy anticonvulsant regime required to control epilepsy, combined with a progressive loss of sodium channel function that occurs with age. References Meisler MH, O’Brien JE, Sharkey LM. Sodium channel gene family: epilepsy mutations, gene interactions and modifier effects. J Physiol 2010;588:1841–1848. Tomlinson SE, Howells J, Burke D. In vivo assessment of neurological channelopathies: Application of peripheral nerve Excitability studies. Neuropharmacology. 2018 Apr;132:98–107. Kiernan MC, Isbister GK, Lin CS, Burke D, Bostock H. Acute tetrodotoxin-induced neurotoxicity after ingestion of puffer fish. Ann Neurol 2005;57:339–48.
-
009 Axonal Excitability properties in dravet s syndrome reflect effect of loss of sodium channels
Journal of Neurology Neurosurgery and Psychiatry, 2019Co-Authors: James Howells, Cindy S.-y. Lin, Michelle A. Farrar, Susan E. Tomlinson, Kate A. Carey, Susanna B. Park, Georgina Hollingsworth, John A. LawsonAbstract:Introduction Mutations in SCN1A encoding the Nav1.1 subunit of the neuronal sodium channel underlie the devastating epilepsy of Dravet’s syndrome.1 The mechanism by which Nav1.1 dysfunction causes seizures is not clear. In vitro and in silico channel evaluation can support mutation pathogenicity but cannot define the in vivo impact of channel dysfunction. Axonal Excitability studies can show the pattern of single-channel dysfunction in disorders where the channel is peripherally expressed.2 This study was undertaken to determine whether Axonal Excitability studies could detect changes in Dravet’s patients related to the condition or due to medication effect. Methods Patients with Dravet’s syndrome were recruited from clinics in Sydney and Melbourne and Axonal Excitability studies were performed. Excitability results were analysed in 3 age groups and compared to age-matched normal controls. Results Twenty six patients (ages 2–46) were studied. Findings were most pronounced in patients aged 20–46 (n=7) with 6.9% greater increase in threshold during hyperpolarization(p=0.1), 7.6% greater threshold decrease on depolarization(p=0.005) and, in the recovery cycle, 19.7% reduction in superExcitability(p=0.002) and 26% reduction in subExcitability(p=0.03). Axonal Excitability studies resembled previously published changes seen in patients with sodium channel blockade caused by acute tetrodotoxin poisoning.3 Conclusions Changes in Excitability of Axonal membrane in Dravet’s syndrome are consistent with a decrease in sodium channel function. As the affected channel in Dravet’s syndrome is not peripherally expressed, the effect seen is likely due to the heavy anticonvulsant regime required to control epilepsy, combined with a progressive loss of sodium channel function that occurs with age. References Meisler MH, O’Brien JE, Sharkey LM. Sodium channel gene family: epilepsy mutations, gene interactions and modifier effects. J Physiol 2010;588:1841–1848. Tomlinson SE, Howells J, Burke D. In vivo assessment of neurological channelopathies: Application of peripheral nerve Excitability studies. Neuropharmacology. 2018 Apr;132:98–107. Kiernan MC, Isbister GK, Lin CS, Burke D, Bostock H. Acute tetrodotoxin-induced neurotoxicity after ingestion of puffer fish. Ann Neurol 2005;57:339–48.
-
Effect of fampridine on Axonal Excitability in multiple sclerosis
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology, 2016Co-Authors: William Huynh, James Howells, Hannah Pickering, Jenna Murray, Christine Cormack, Cindy S.-y. Lin, Steve Vucic, Matthew C. Kiernan, Arun V. KrishnanAbstract:Abstract Objective To investigate the effects of fampridine on nerve Excitability, the present study utilized peripheral Axonal Excitability techniques in 18 MS patients receiving treatment with fampridine. Methods Studies were performed at baseline and repeated 3months after institution of fampridine at standard dosing. Results Following treatment with fampridine there were significant changes in Axonal Excitability for those parameters associated with fast K + channels that shifted towards normal control values. Specifically, increases were noted in the peak superExcitability of recovery cycle (fampridine, −25.6±1.6%; baseline −22.8±1.7%; p p p =0.02). Conclusion The present study has established that fampridine at standard doses exerts effects on peripheral nerve function that may be mediated by reduction of fast K + conductances. Significance Modulation of fast K + conductances by fampridine may contribute to the improvement observed in MS symptoms including motor fatigue.
-
Axonal Excitability: molecular basis and assessment in the clinic
Oxford Medicine Online, 2016Co-Authors: Susanna B. Park, Cindy S.-y. Lin, Matthew C. KiernanAbstract:Axonal Excitability techniques were developed to assess Axonal resting membrane potential and ion channel function in vivo, and thereby provide greater molecular understanding of the activity of voltage gated ion channels and ion pumps underlying nerve and membrane function. Axonal Excitability studies provide complimentary information to conventional nerve conduction studies, using submaximal stimuli to examine the properties underlying the Excitability of the axon. Such techniques have been developed both as a research technique to examine disease pathophysiology and as a clinical investigation technique. This chapter provides an overview of Axonal Excitability techniques, addressing the role of key ion channels and pumps in membrane function and highlighting examples of clinical case studies, where such techniques have been utilized, including motor neuronopathies, tracking progression of chemotherapy-induced peripheral neuropathy, and assessing treatment response in chronic inflammatory demyelinating polyneuropathy.
-
In vivo evidence of reduced nodal and paranodal conductances in type 1 diabetes.
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology, 2015Co-Authors: Natalie Kwai, James Howells, Cindy S.-y. Lin, Matthew C. Kiernan, Ria Arnold, Ann M. Poynten, Arun V. KrishnanAbstract:Abstract Objectives Diabetic neuropathy is a debilitating complication of diabetes. Animal models of type 1 diabetes (T1DM) suggest that functional and structural changes, specifically axo-glial dysjunction, may contribute to neuropathy development. The present study sought to examine and characterise early sensory Axonal function in T1DM patients in the absence of clinical neuropathy. Methods Thirty patients with T1DM (15M:15F) without neuropathy underwent median nerve sensory and motor Axonal Excitability studies to examine Axonal function. A verified mathematical model of human motor and sensory axons was used to elucidate the underlying causes of observed alterations. Results Compared to controls (NC), T1DM patients demonstrated significant Axonal Excitability abnormalities in sensory and motor axons. These included marked reductions in sensory and motor subExcitability during the recovery cycle (T1DM 7.9 ± 0.4:10.4 ± 0.6%, NC 10.4 ± 0.7:15.4 ± 1.2%, P 0.01) and during hyperpolarizing threshold electrotonus at 10–20 ms (T1DM −75.5 ± 0.8:−69.7 ± 0.8%, NC −78.4 ± 1:−72.7 ± 0.9%, P 0.01). Mathematical modelling demonstrated that these changes were due to reduced nodal Na + currents, nodal/paranodal K + conductances and Na + /K + pump dysfunction, consistent with axo-glial dysjunction as outlined in animal models of T1DM. Conclusions The study provided support for the occurrence of early changes in nodal and paranodal conductances in patients with T1DM. Significance These data indicate that Axonal Excitability techniques may detect early changes in diabetic patients, providing a window of opportunity for prophylactic intervention in T1DM.
Satoshi Kuwabara - One of the best experts on this subject based on the ideXlab platform.
-
sensory and motor Axonal Excitability testing in early diabetic neuropathy
Clinical Neurophysiology, 2021Co-Authors: Satoshi Kuwabara, Alexander Gramm Kristensen, S Gylfadottir, Mustapha Itani, Thomas Kroigard, Karolina Snopek Khan, Nanna B FinnerupAbstract:Abstract Objective The aim of the present study was to gain insight into the pathophysiology of diabetic polyneuropathy (DPN) and examine the diagnostic value of sensory and motor Axonal Excitability testing. Methods One hundred and eleven type 2 diabetics with and without DPN (disease duration: 6.36 ± 0.25 years) and 60 controls were included. All participants received a thorough clinical examination including Michigan Neuropathy Screening Instrument (MNSI) score, nerve conduction studies (NCS), and sensory and motor Excitability tests. Patients were compared by the likelihood of neuropathy presence, ranging from no DPN (17), possible/probable DPN (46) to NCS-confirmed DPN (48). Results Motor Excitability tests showed differences in rheobase and depolarizing threshold electrotonus measures between NCS-confirmed DPN group and controls but no changes in hyperpolarising threshold electrotonus or recovery cycle parameters. Sensory Excitability showed even less changes despite pronounced sensory NCS abnormalities. There were only weak correlations between the above motor Excitability parameters and clinical scores. Conclusions Changes in Excitability in the examined patient group were subtle, perhaps because of the relatively short disease duration. Significance Less pronounced Excitability changes than NCS suggest that Axonal Excitability testing is not of diagnostic value for early DPN and does not provide information on the mechanisms.
-
Measurement of Axonal Excitability: Consensus guidelines.
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology, 2019Co-Authors: Matthew C. Kiernan, Satoshi Kuwabara, Sonoko Misawa, Christian Krarup, Arun V. Krishnan, Susanna B. Park, Hugh Bostock, Ryuji Kaji, Cindy Shin Yi Lin, Mihai MoldovanAbstract:Abstract Measurement of Axonal Excitability provides an in vivo indication of the properties of the nerve membrane and of the ion channels expressed on these axons. Axonal Excitability techniques have been utilised to investigate the pathophysiological mechanisms underlying neurological diseases. This document presents guidelines derived for such studies, based on a consensus of international experts, and highlights the potential difficulties when interpreting abnormalities in diseased axons. The present manuscript provides a state-of-the-art review of the findings of Axonal Excitability studies and their interpretation, in addition to suggesting guidelines for the optimal performance of Excitability studies.
-
T38. Altered Axonal Excitability in spinal and bulbar muscular atrophy
Clinical Neurophysiology, 2018Co-Authors: Kazumoto Shibuya, Sonoko Misawa, Yukari Sekiguchi, Yoichi Suzuki, Hioroshi Amino, Tomoki Suichi, Atsuko Tsuneyama, Satoshi KuwabaraAbstract:Introduction Spinal and bulbar muscular atrophy (SBMA) is an inherited motor neuron disease characterized with prominent fasciculations. Fasciculations suggest motor nerve hyperExcitability and potentially result in a burden to motor neuron. Methods Axonal Excitability and nerve conduction studies were performed in 31 patients with SBMA and 140 with amyotrophic lateral sclerosis (ALS). These results were compared with those of 16 healthy males (HM). In SBMA, correlations between neurophysiological studies and clinical profiles were examined. Results Patient backgrounds in SBMA were as follows; mean age; 58 years, mean disease duration; 152 months, mean ALS functional rating scale (ALSFRS-R); 41, mean CAG repeat expansion; 46, mean compound muscle action potential (CMAP) amplitude on abductor pollicis brevis muscle was 6.0 mV. Compared with HM, SBMA patients had longer strength-duration time constant (SDTC), greater threshold change in depolarizing threshold electrotonus (TEd) and greater supernormality (all p p R = 0.42, p R = −0.52, p R = −0.46, p p p p p Conclusion A previous study investigated Axonal excitabilities in 7 patients with SBMA and revealed increased sodium currents. Our findings suggest that SBMA patients have increased sodium and decreased fast potassium currents. Similar findings and decreased slow potassium currents were found in ALS. This difference may suggest that ALS patients have more hyperexcitable motor nerve. Moreover, our findings suggest that decreased fast potassium currents are related to CAG repeat expansion in SBMA. It is already reported that SBMA patients have disruption of Axonal transport. CAG repeat expansion may bring about Axonal hyperExcitability and result in a burden to motor neuron.
-
Altered Axonal Excitability properties and nerve edema in POEMS syndrome
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology, 2015Co-Authors: Satsuki Mitsuma, Sonoko Misawa, Sagiri Isose, Kazumoto Shibuya, Yukari Sekiguchi, Yuta Iwai, Minako Beppu, Keisuke Watanabe, Hiroshi Amino, Satoshi KuwabaraAbstract:Abstract Objective POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) syndrome is a rare cause of demyelinating neuropathy with upregulation of vascular endothelial growth factor (VEGF). This study aimed to elucidate Axonal Excitability properties and their relation to VEGF levels and nerve edema in POEMS neuropathy. Methods Axonal Excitability measurement and nerve ultrasound were performed in the median nerve of 33 patients with POEMS syndrome. Serum VEGF levels were measured by ELISA. Results Compared with normal subjects ( n =87), POEMS patients showed longer strength-duration time constant, fanning-out of threshold electrotonus curves, and greater threshold changes in a hyperpolarizing current–threshold relationship. Nerve ultrasound showed significant enlargement in POEMS patients. Serum VEGF levels and the extent of nerve edema partly correlated with nerve conduction slowing, as well as persistent sodium currents and inward rectification. Conclusions In POEMS syndrome, patterns of changes in Excitability properties could suggest increased persistent sodium currents, and impaired potassium and inward rectifying channels. The findings were not consistent with depolarization due to nerve edema and compression ischemia. Significance In addition to demyelination, nerve edema induced by upregulated VEGF, and upregulated inflammatory cytokines could modulate profiles of POEMS neuropathy.
-
Acquired and genetic channelopathies: in vivo assessment of Axonal Excitability.
Experimental Neurology, 2015Co-Authors: Satoshi Kuwabara, Sonoko MisawaAbstract:Neuronal or Axonal ion channel function can be impaired or altered in a number of disorders, such as acquired (autoantibody-mediated, toxic, and metabolic) and genetic channelopathies, and even neurodegenerative (motor neuron disease) or inflammatory diseases (multiple sclerosis, immune-mediated neuropathies). When specific channels are affected, Axonal/neuronal Excitability primarily alters according to original function of the corresponding channels. Separately, in the 1990s, Axonal Excitability testing was developed to assess ion channel function, membrane potential, and passive membrane properties non-invasively in human subjects. Using this technique, numerous papers on altered Axonal Excitability in a variety of disorders have been published since 2000. In a recent issue of Experimental Neurology, Park et al. demonstrated changes in peripheral Axonal Excitability in limbic encephalitis and acquired neuromyotonia with anti-voltage gated potassium channel antibodies. Unexpectedly, the results were not consistent with those caused by simple potassium channel blockade, suggesting that multiple other factors contribute to altered Axonal Excitability. In contrast it was reported that patients with episodic ataxia type 1 (genetic channelopathy with mutation of Kv1.1 channel gene) show prominent Excitability changes exactly compatible with fast potassium channel blockade. This commentary aims to highlight findings of this study in a broader context, and provides possible explanations for the discrepancy of patterns of Axonal Excitability changes in acquired and genetic potassium channelopathies.
Hilmi Uysal - One of the best experts on this subject based on the ideXlab platform.
-
P43-T Axonal Excitability findings in familial dyslipidemia
Clinical Neurophysiology, 2019Co-Authors: Abir Alaamel, Gizem Kızılay, Ibrahim Basarici, Hasan Altunbas, Hilmi UysalAbstract:Background Cholesterol is one of the most important components of the myelin sheath. Schwann cells are responsible for myelinization of peripheral nerves. All situations that disrupt cholesterol metabolism in Schwann cells may affect channel dynamics on peripheral axons. Cholesterol entrance into the cell has been impaired due to genetic defects in apoproteins or its receptors in familial dyslipidemia patients. This is why we aimed to study the effects of this possible metabolic impairment on familial dyslipidemia patients. We have been investigated motor and sensorial Axonal Excitability parameters. Material and methods We have evaluated median nerve motor and sensory Axonal Excitability parameters of patients diagnosed with familial dyslipidemia or investigated for familial dyslipidemia according to National Lipid Association screening and Simon Broome criteria by using Q-trackS software and compared with control group. Results There was a statistically significant difference in the refractory period in 2 ms (p = 0.0429, p = 0.00281) when the familial dyslipidemia group and control group were compared in terms of both sensory and motor electrophysiological parameters. Conclusions In patients with familial dyslipidemia, we have found that the refractory period is shorter than the control group in both sensory and motor electrophysiological parameters of the median nerve. This finding may suggest that the median nerve axons in these patients are hyperpolarized state than normal. This study is supported by TUBITAK.
-
Tibial nerve Axonal Excitability in type 1 diabetes mellitus.
Muscle & nerve, 2018Co-Authors: Pinar Gencpinar, Gamze Celmeli, Ozgur Duman, Şenay Haspolat, Hilmi UysalAbstract:INTRODUCTION The aim of this study was to determine alterations in Axonal Excitability in tibial nerve as compared with median nerve Axonal Excitability in patients with diabetic polyneuropathy. METHODS Six patients with diabetic polyneuropathy and 10 patients with diabetes mellitus without polyneuropathy were enrolled. RESULTS Compared with diabetic patients without polyneuropathy, the tibial nerve strength-duration time constant was significantly longer and supernormality was lower in those with polyneuropathy. Threshold electrotonus studies showed abnormalities in patients with diabetic polyneuropathy, in which smaller threshold changes from long-depolarizing and hyperpolarizing conditioning, termed "fanning-in," were found. DISCUSSION This study confirms that Axonal Excitability is significantly altered in the tibial nerve of patients with diabetic polyneuropathy. Evaluating the Axonal Excitability of the median and tibial nerves may reveal the presence of length-dependent polyneuropathy at an early stage. Muscle Nerve 59:76-81, 2019.
-
p237 Axonal Excitability findings in type 1 diabetes mellitus median nerve versus tibial nerve comparison
Clinical Neurophysiology, 2017Co-Authors: Pinar Gencpinar, Gamze Celmeli, Ozgur Duman, Şenay Haspolat, Abir Alaamel, Gizem Kızılay, Hilmi UysalAbstract:Objective Length dependent peripheral neuropathy is the most common complication of diabetes mellitus (DM). As no curative treatment for diabetic polyneuropathy (DMP) is available, its prevention and early detection is very important. Axonal Excitability is defined as the capability of nodal and paranodal pathological changes in DMP. The aim of present study was to determine alterations in Axonal Excitability findings in tibial nerve by comparing median nerve Axonal Excitability findings in Type 1 DMP. Methods The total 284 patients, who were followed up for Type 1 DM according to criteria of American Diabetes Association, were screened in this study. Six DMP patients, 10 random non-polyneuropathy cases and 14 healthy control subjects were examined by threshold tracking method (TROND protokol) from median and tibial nerve. Results Even if there is not prominent difference in median nerve Axonal Excitability studies in PNP and DM patients there was prominent pathological findings in tibial nerve. The strength–duration time constant was significantly longer in DPN Type 1 patients than in normal patients. Supernormality was significantly smaller in DPN patients. Threshold electrotonus studies showed abnormalities in patients with DPN that smaller threshold changes by long depolarizing and hyperpolarizing conditioning current named as “fanning-in”. Conclusion This study confirms that there was significantly alteration in Axonal Excitability findings in DMP in tibial nerve. Comparisons median and tibial nerve Axonal Excitability findings have potential to show the length dependent polyneuropathic pathological status in Axonal Excitability studies.
-
P237 Axonal Excitability findings in type 1 diabetes mellitus – Median nerve versus tibial nerve comparison
Clinical Neurophysiology, 2017Co-Authors: Pinar Gencpinar, Gamze Celmeli, Ozgur Duman, Şenay Haspolat, Abir Alaamel, Gizem Kızılay, Hilmi UysalAbstract:Objective Length dependent peripheral neuropathy is the most common complication of diabetes mellitus (DM). As no curative treatment for diabetic polyneuropathy (DMP) is available, its prevention and early detection is very important. Axonal Excitability is defined as the capability of nodal and paranodal pathological changes in DMP. The aim of present study was to determine alterations in Axonal Excitability findings in tibial nerve by comparing median nerve Axonal Excitability findings in Type 1 DMP. Methods The total 284 patients, who were followed up for Type 1 DM according to criteria of American Diabetes Association, were screened in this study. Six DMP patients, 10 random non-polyneuropathy cases and 14 healthy control subjects were examined by threshold tracking method (TROND protokol) from median and tibial nerve. Results Even if there is not prominent difference in median nerve Axonal Excitability studies in PNP and DM patients there was prominent pathological findings in tibial nerve. The strength–duration time constant was significantly longer in DPN Type 1 patients than in normal patients. Supernormality was significantly smaller in DPN patients. Threshold electrotonus studies showed abnormalities in patients with DPN that smaller threshold changes by long depolarizing and hyperpolarizing conditioning current named as “fanning-in”. Conclusion This study confirms that there was significantly alteration in Axonal Excitability findings in DMP in tibial nerve. Comparisons median and tibial nerve Axonal Excitability findings have potential to show the length dependent polyneuropathic pathological status in Axonal Excitability studies.
-
S119 Axonal Excitability studies in diabetic neuropathy
Clinical Neurophysiology, 2017Co-Authors: Hilmi UysalAbstract:Diabetic polyneuropathy (DPN) is a complication of diabetes involving complex mechanisms. The introduction of automated threshold-tracking has led to a number of abnormal Axonal Excitability findings associated with diabetes without neuropathy (DWN) and DPN. The first abnormality described was a striking resistance to ischaemia in DWN. SuperExcitability measurements showed that this ischaemic resistance was not due to a depolarized resting potential, but was related to the mean blood glucose over 24 h, indicating a rapid effect of glucose on nerve metabolism. Glycaemic control by insulin treatment in patients with diabetic neuropathy restored sensitivity to ischaemia. In contrast to DWN, patients with established DPN exhibited ‘fanning-in’ of threshold electrotonus and reduced superExcitability, indicating membrane depolarization. Using the rate of recovery of Excitability following maximum voluntary contraction as a measure of electrogenic sodium pump activity, Excitability measurements indicated that sodium pump function was normal in DWN, but reduced in DPN, accounting for the membrane depolarization. Further Excitability studies have attempted to determine changes, other than resistance to ischaemia, that precede the development of neuropathy. Evidence that depolarization precedes neuropathy has been found both in Type 1 and Type 2 diabetics. An ischaemic cause was suggested by the finding that Excitability abnormalities correlated better with vascular-related factors than with HgbA1c. Recently Excitability studies have moved on from assessing pathophysiology to treatment. In Type 1 DWN, glycaemic control by continuous insulin infusion preserved membrane potential much better than comparable control by multiple injections, perhaps because glucose variability can cause microvascular dysfunction.