%0 Journal Article
%~ PubMed
%A Ng, Karl
%A Howells, James
%A Pollard, John D
%A Burke, David
%T Different mechanisms underlying changes in excitability of peripheral nerve sensory and motor axons in multiple sclerosis.
%B Muscle & Nerve
%D 2013
%C United States
%I John Wiley & Sons, Inc.
%V 47
%N 1
%P 53-60
%@ 0148-639X
%X 
%Z FOR Codes: 110903 111603


%0 Journal Article
%~ PubMed
%A Jankelowitz, S K
%A Spies, J M
%A Burke, D
%T Late-onset neurological symptoms in thalidomide-exposed subjects: a study of an Australasian cohort.
%B European Journal of Neurology
%D 2013
%C United States
%I Wiley-Blackwell Publishing Ltd.
%V 20
%N 3
%P 509-514
%@ 1468-1331
%X 
%Z FOR Codes: 110904 110399


%0 Journal Article
%~ PubMed
%A Burke, David
%A Wissel, Jörg
%A Donnan, Geoffrey A
%T Pathophysiology of spasticity in stroke.
%B Neurology
%D 2013
%C United States
%I Lippincott Williams & Wilkins
%V 80
%N 3 Suppl 2
%P S20-26
%@ 1526-632X
%X 
%Z FOR Codes: 110321 110903 111603


%0 Journal Article
%~ PubMed
%A Jankelowitz, Stacey K
%A Burke, David
%T Do the motor manifestations of parkinson disease alter motor axon excitability?
%B Muscle & Nerve
%D 2012
%C United States
%I John Wiley & Sons, Inc.
%V 45
%N 1
%P 43-47
%@ 0148-639X
%X Background: Axonal excitability is altered in common medical conditions such as stroke, multiple sclerosis, and spinal cord injury. Given the motor neuron changes in the presence of rigidity and tremor in Parkinson disease, we examine whether there are also changes in motor axon excitability. Methods: Axonal excitability studies were performed in 15 Parkinson subjects and 12 age-matched control subjects. Results: There was no significant difference in excitability indices between Parkinson subjects and control subjects. Conclusions: It is unlikely that the lack of change in the excitability indices reflects a balance between the effects of bradykinesia ("underactivity") and the effects of rigidity and tremor ("overactivity") on the motoneuron and its axon. It is more likely that plastic changes in motoneuron properties do not occur symmetrically with decreases and increases in activity, being more profound when activity levels are interrupted and less obvious when they are enhanced. Muscle Nerve 45: 43-47, 2012.
%Z FOR Codes: 111603 110905


%0 Journal Article
%~ PubMed
%A Giboin, Louis-Solas
%A Lackmy-Vallée, Alexandra
%A Burke, David
%A Marchand-Pauvert, Veronique
%T Enhanced propriospinal excitation from hand muscles to wrist flexors during reach-to-grasp in humans.
%B Journal of Neurophysiology
%D 2012
%C United States
%I American Physiological Society
%V 107
%N 2
%P 532-543
%@ 1522-1598
%X In humans, propriospinal neurons located at midcervical levels receive peripheral and corticospinal inputs and probably participate in the control of grip tasks, but their role in reaching movements, as observed in cats and primates, is still an open question. The effect of ulnar nerve stimulation on flexor carpi radialis (FCR) motor evoked potential (MEP) was tested during reaching tasks and tonic wrist flexion. Significant MEP facilitation was observed at the end of reach during reach-to-grasp but not during grasp, reach-to-point, or tonic contractions. MEP facilitation occurred at a longer interstimulus interval than expected for convergence of corticospinal and afferent volleys at motoneuron level and was not paralleled by a change in the H-reflex. These findings suggest convergence of the two volleys at propriospinal level. Ulnar-induced MEP facilitation was observed when conditioning stimuli were at 0.75 motor response threshold (MT), but not 1 MT. This favors an increased excitability of propriospinal neurons rather than depression of their feedback inhibition, as has been observed during tonic power grip tasks. It is suggested that the ulnar-induced facilitation of FCR MEP during reach may be due to descending activation of propriospinal neurons, assisting the early recruitment of large motoneurons for rapid movement. Because the feedback inhibitory control is still open, this excitation can be truncated by cutaneous inputs from the palmar side of the hand during grasp, thus assisting movement termination. It is concluded that the feedforward activation of propriospinal neurons and their feedback control may be involved in the internal model, motor planning, and online adjustments for reach-to-grasp movements in humans.
%Z FOR Codes: 111603 110603


%0 Journal Article
%~ PubMed
%A Tomlinson, Susan E
%A Bostock, Hugh
%A Grinton, Bronwyn
%A G Hanna, Michael
%A Kullmann, Dimitri M
%A Kiernan, Matthew C
%A Scheffer, Ingrid E
%A Berkovic, Samuel F
%A Burke, David
%T In vivo loss of slow potassium channel activity in individuals with benign familial neonatal epilepsy in remission.
%B Brain
%D 2012
%C United Kingdom
%I Oxford University Press
%V 135
%N Pt 10
%P 3144-3152
%@ 1460-2156
%X 
%Z FOR Codes: 110904 111603


%0 Journal Article
%~ PubMed
%A Burke, David
%A Phillips, Lawrence H
%T Is the "impact factor" a valid measure of the impact of research published in Clinical Neurophysiology and Muscle & Nerve?
%B Clinical Neurophysiology
%D 2012
%C Ireland
%I Elsevier Ireland Ltd
%V 123
%N 9
%P 1687-1690
%@ 1872-8952
%X 
%Z FOR Codes: 110999 10499 111603


%0 Journal Article
%~ PubMed
%A Burke, David
%A Phillips, Lawrence H
%T Is the "impact factor" a valid measure of the impact of research published in Clinical Neurophysiology and Muscle & Nerve?
%B Muscle & Nerve
%D 2012
%C United States
%I John Wiley & Sons, Inc.
%V 46
%N 3
%P 309-312
%@ 0148-639X
%X 
%Z FOR Codes: 80705 111699 110999 80705 111603 110999


%0 Book Section
%A Burke, David
%T Microneurography and its potential clinical applications
%B Aminoff's Electrodiagnosis in Clinical Neurology
%D 2012
%C United States
%I Saunders (Elsevier)
%V 
%N 
%P 327-344
%@ 9781455703081
%E Aminoff, Michael J
%X 
%Z FOR Codes: 110903


%0 Journal Article
%~ PubMed
%A Kumar, Kishore R
%A Sue, Carolyn M
%A Burke, David
%A Ng, Karl
%T Peripheral neuropathy in hereditary spastic paraplegia due to spastin (SPG4) mutation - A neurophysiological study using excitability techniques.
%B Clinical Neurophysiology
%D 2012
%C Ireland
%I Elsevier Ireland Ltd
%V 123
%N 7
%P 1454-1459
%@ 1872-8952
%X OBJECTIVE: To identify peripheral nerve abnormalities in hereditary spastic paraplegia (HSP) due to mutations in the spastin gene (spastic paraplegia 4, SPG4) using standard nerve conduction (NCS) and novel tests of axonal excitability. METHODS: Eleven patients with known mutations in spastin were assessed with NCS for the upper and lower limbs, and axonal excitability testing on the median nerve. RESULTS: Standard nerve conduction studies revealed a sensorimotor neuropathy in two patients. Excitability studies on median motor axons showed an isolated abnormality (increased strength-duration time constant), but those on sensory axons were normal in nine patients with normal routine nerve conduction studies. CONCLUSIONS: Peripheral neuropathy occurs in HSP patients with SPG4 mutations, but axonal excitability studies provide limited additional evidence for subclinical peripheral nerve dysfunction, and add little further to standard nerve conduction studies. SIGNIFICANCE: The features of HSP due to SPG4 mutations include sensorimotor polyneuropathy. The value of excitability studies is limited in individual patients.
%Z FOR Codes: 111603 110905


%0 Journal Article
%~ PubMed
%A Burke, David
%A Phillips, Lawrence H
%T Reply: Use and misuse of impact factors.
%B Muscle & Nerve
%D 2012
%C United States
%I John Wiley & Sons, Inc.
%V 46
%N 6
%P 979-980
%@ 0148-639X
%X 
%Z FOR Codes: 80609 80702


%0 Book
%A Pierrot-Deseilligny, Emmanuel
%A Burke, David
%T The Circuitry of the Human Spinal Cord: Spinal and Corticospinal Mechanisms of Movement
%B 
%D 2012
%C United States
%I Cambridge University Press
%V 
%N 
%P 
%@ 9780521192583
%X 
%Z FOR Codes: 110903


%0 Journal Article
%~ PubMed
%A McNulty, Penelope A
%A Shiner, Christine T
%A Thayaparan, Ganesha K
%A Burke, David
%T The stability of M(max) and H (max) amplitude over time.
%B Experimental Brain Research
%D 2012
%C Germany
%I Springer
%V 218
%N 4
%P 601-607
%@ 1432-1106
%X The stability of the maximal muscle response (M(max)) is critical to H reflex methodology. It has previously been reported that the amplitude of M(max) declines over time. If reproducible, this finding would have implications for all experimental studies that normalise the output of the motoneurone pool against the M wave. We investigated the effect of time on changes in M(max) and the maximal H reflex (H(max)) evoked at 4-s intervals over 60 min. To identify an influence of homosynaptic depression, we extended the interstimulus interval to 10 s and the time to 100 min. Two recording montages over soleus were used to ensure that interelectrode distance was not a critical factor. The soleus M(max) and H reflex were evoked by stimulation of the tibial nerve in the popliteal fossa in 7 subjects who sat with the knee flexed to 30° and the ankle plantar flexed by ~30°. We found no change in the pooled data for M(max), H(max), a reflex 50% of maximal, or the current required to produce it. However, one subject had a statistically significant increase in M(max) and a concurrent decrease in H(max) regardless of the interstimulus interval. On average, there was no change in the H(max)/M(max) ratio over time. While both M(max) and H(max) may change in response to many factors, these results suggest that, typically, time is not one of them.
%Z FOR Codes: 111603 110903


%0 Journal Article
%~ PubMed
%A Howells, James
%A Trevillion, Louise
%A Bostock, Hugh
%A Burke, David
%T The voltage dependence of Ih in human myelinated axons.
%B Journal of Physiology
%D 2012
%C United Kingdom
%I Wiley-Blackwell Publishing Ltd.
%V 590
%N 7
%P 1625-1640
%@ 1469-7793
%X HCN channels are responsible for I(h), a voltage-gated inwardly rectifying current activated by hyperpolarization. This current appears to be more active in human sensory axons than motor and may play a role in the determination of threshold. Differences in I(h) are likely to be responsible for the high variability in accommodation to hyperpolarization seen in different subjects. The aim of this study was to characterise this current in human axons, both motor and sensory. Recordings of multiple axonal excitability properties were performed in ten subjects, with a focus on the changes in threshold evoked by longer and stronger hyperpolarizing currents than normally studied. The findings confirm that accommodation to hyperpolarization is greater in sensory than motor axons in all subjects, but the variability between subjects was greater than the modality difference. An existing model of motor axons was modified to take into account the behaviour seen with longer and stronger hyperpolarization, and a mathematical model of human sensory axons was developed based on the data collected. The differences in behaviour of sensory and motor axons and the differences between different subjects are best explained by modulation of the voltage dependence, along with a modest increase of expression of the underlying conductance of I(h). Accommodation to hyperpolarization for the mean sensory data is fitted well with a value of -94.2 mV for the mid-point of activation (V(0.5)) of I(h) as compared to -107.3 mV for the mean motor data. The variation in response to hyperpolarization between subjects is accounted for by varying this parameter for each modality (sensory: -89.2 to -104.2 mV; motor -87.3 to -127.3 mV). These voltage differences are within the range that has been described for physiological modulation of I(h) function. The presence of slowly activated I(h) isoforms on both motor and sensory axons was suggested by modelling a large internodal leak current and a masking of the Na(+)/K(+)-ATPase pump activity by a tonic depolarization. In addition to an increased activation of I(h), the modelling suggests that in sensory axons the nodal slow K(+) conductance is reduced, with consequent depolarization of resting membrane potential, and action potential of shorter duration.
%Z FOR Codes: 60699 111603 110905


%0 Journal Article
%~ PubMed
%A Park, Susanna B
%A Lin, Cindy S-Y
%A Burke, David
%A Kiernan, Matthew C
%T Activity-dependent conduction failure: molecular insights.
%B Journal of the Peripheral Nervous System
%D 2011
%C United States
%I Wiley-Blackwell Publishing, Inc.
%V 16
%N 3
%P 159-168
%@ 1529-8027
%X Weakness and fatigue are commonly encountered symptoms in neurological disorders and significantly impair quality of life. In the case of motor axons, conduction block contributes to weakness and fatigue and may be associated with aberrant nerve activity including fasciculations and cramp. These symptoms result from dysfunction of the constituent channels and pumps of the axonal membrane. In critically conducting axons, impulse conduction can be impaired by the effects of activity or by other mechanisms that produce a significant shift in membrane potential. Conduction failure may be accentuated or relieved by maneuvers that manipulate the time course of the driving current, including the administration of agents that interfere with Na(+)  channel function. In patients with inflammatory neuropathies, normal activity may be sufficient to precipitate conduction failure at sites of impaired function in multifocal motor neuropathy (MMN) and chronic inflammatory demyelinating polyneuropathy (CIDP). From a clinical perspective, these features are not assessed adequately by conventional neurophysiological techniques. As weakness and fatigue may only develop following activity or exertion, it is useful to assess the effects of impulse trains to determine the extent of conduction failure and the resulting symptoms in neurological patients. These techniques and the physiological mechanisms underlying the development of activity-dependent hyperpolarization will be critically appraised in this review, with a focus on demyelinating neuropathies, MMN and the neurodegenerative disease, and amyotrophic lateral sclerosis (ALS).
%Z FOR Codes: 111603 110905


%0 Journal Article
%~ PubMed
%A Kumar, Kishore R
%A Liang, Christina
%A Needham, Merilee
%A Burke, David
%A Sue, Carolyn M
%A Ng, Karl
%T Axonal hyperpolarization in inclusion-body myopathy, paget disease of the bone, and frontotemporal dementia (IBMPFD).
%B Muscle & Nerve
%D 2011
%C United States
%I John Wiley & Sons, Inc.
%V 44
%N 2
%P 191-196
%@ 0148-639X
%X Inclusion-body myopathy, Paget disease of the bone, and frontotemporal dementia (IBMPFD) is an autosomal dominant disorder due to mutations in the valosin-containing protein (VCP) gene. Patients with this disorder may have neuropathic or myopathic features.
%Z FOR Codes: 30405 110399 110905


%0 Journal Article
%~ PubMed
%A Barnett, Michael H
%A Barnett, Yael
%A Burke, David
%A Willison, Hugh
%T Spinal nerve root hypertrophy in chronic ataxic neuropathy with antiglycolipid IgM antibodies.
%B Journal of Neurology, Neurosurgery, and Psychiatry
%D 2011
%C United Kingdom
%I BMJ Group
%V 82
%N 1
%P 97
%@ 1468-330X
%X 
%Z FOR Codes: 110905


%0 Journal Article
%A Trevillion, Louise
%A Howells, James (Tim)
%A Tomlinson, Susan
%A Bostock, Hugh
%A Burke, David
%T What makes some axons more excitable than others?
%B Physiology News
%D 2011
%C United Kingdom
%I The Physiological Society
%V 82
%N 
%P 32-35
%@ 1476-7996
%X 
%Z FOR Codes: 110906


%0 Journal Article
%~ PubMed
%A Ng, Karl
%A Kumar, Kishore
%A Brew, Bruce
%A Burke, David
%T Axonal excitability in viral polyneuropathy and nucleoside neuropathy in HIV patients.
%B Journal of Neurology, Neurosurgery, and Psychiatry
%D 2010
%C United Kingdom
%I BMJ Group
%V 82
%N 9
%P 978-980
%@ 1468-330X
%X HIV infection is associated with several forms of peripheral neuropathy, the most common being a distal symmetrical polyneuropathy due to HIV infection (''DSP''). Direct viral effects are an important cause (hereafter termed viral neuropathy (VN)), but sometimes, it is due to nucleoside antiretroviral drug therapy (nucleoside neuropathy (NN)). Mechanisms of disease are incompletely understood, with some evidence implicating HIV envelope glycoprotein gp120 mediated neuronal apoptosis for the former and mitochondrial toxicity ?? DNA polymerase ?? involvement in the latter. The authors studied 16 HIV positive patients, 14 of whom had neuropathy (10 VN; 4 NN), clinically, with conventional nerve-conduction studies (NCS), and with measurements of the excitability of motor and sensory axons in the median nerve. Clinically neuropathic patients were all symptomatic, and 12 had abnormalities in NCS. There were no changes in the excitability of sensory or motor axons in VN, but there were in the NN group. These were consistent with depolarisation of the internodal membrane (''fanned in'' threshold electrotonus, increased resting current--voltage slope, reduced superexcitability) but with sparing of nodal properties (absolute threshold, strength--duration properties, refractoriness). Membrane abnormalities in VN are not diffuse and are likely to result from a more focal process, presumably proximal, while those in NN most likely relate to mitochondrial dysfunction. Confirmation of these findings may allow neurophysiological distinction between these entities.
%Z FOR Codes: 111603 110905


%0 Journal Article
%~ PubMed
%A Burke, David
%A Pierrot-Deseilligny, Emmanuel
%T Caveats when studying motor cortex excitability and the cortical control of movement using transcranial magnetic stimulation.
%B Clinical Neurophysiology
%D 2010
%C Ireland
%I Elsevier Ireland Ltd
%V 121
%N 2
%P 121-123
%@ 1872-8952
%X 
%Z FOR Codes: 111603 60699 110903


%0 Journal Article
%~ PubMed
%A Vucic, Steve
%A Burke, David
%A Kiernan, Matthew C
%T Fatigue in Multiple Sclerosis: Mechanisms and Management.
%B Clinical Neurophysiology
%D 2010
%C Ireland
%I Elsevier Ireland Ltd
%V 121
%N 6
%P 809-817
%@ 1872-8952
%X Multiple sclerosis [MS] is a chronic immune-mediated disorder of the central nervous system [CNS]. Fatigue may be a debilitating symptom in MS patients, adversely impacting on their quality of life. Clinically, fatigue may manifest as exhaustion, lack of energy, increased somnolence, or worsening of MS symptoms. Activity and heat typically serve to exacerbate symptoms of fatigue. There is now strong evidence to suggest that fatigue results from reduced voluntary activation of muscles by means of central mechanisms. Given that axonal demyelination is a pathological hallmark of MS, activity-dependent conduction block [ADCB] has been proposed as a mechanism underlying fatigue in MS. This ADCB results from axonal membrane hyperpolarization, mediated by the Na(+)/K(+) electrogenic pump, with conduction failure precipitated in demyelinated axons with a reduced safety factor of impulse transmission. In addition, Na(+)/K(+) pump dysfunction, as reported in MS, may induce a depolarizing conduction block associated with inactivation of Na(+) channels. These processes may induce secondary effects including axonal degeneration triggered by raised levels of intracellular Ca(2+) through reverse operation of the Na(+)-Ca(2+) exchanger. Restoration of normal conduction in demyelinated axons with selective channel blockers improves fatigue and may yet prove useful as a neuroprotective strategy, in preventing secondary axonal degeneration and consequent functional impairment.
%Z FOR Codes: 110399 110903 111603


%0 Journal Article
%~ PubMed
%A Tomlinson, Susan E
%A Tan, S Veronica
%A Kullmann, Dimitri M
%A Griggs, Robert C
%A Burke, David
%A Hanna, Michael G
%A Bostock, Hugh
%T Nerve excitability studies characterize KV1.1 fast potassium channel dysfunction in patients with episodic ataxia type 1.
%B Brain
%D 2010
%C United Kingdom
%I Oxford University Press
%V 133
%N Pt 12
%P 3530-3540
%@ 1460-2156
%X Episodic ataxia type 1 is a neuronal channelopathy caused by mutations in the KCNA1 gene encoding the fast K(+) channel subunit K(v)1.1. Episodic ataxia type 1 presents with brief episodes of cerebellar dysfunction and persistent neuromyotonia and is associated with an increased incidence of epilepsy. In myelinated peripheral nerve, K(v)1.1 is highly expressed in the juxtaparanodal axon, where potassium channels limit the depolarizing afterpotential and the effects of depolarizing currents. Axonal excitability studies were performed on patients with genetically confirmed episodic ataxia type 1 to characterize the effects of K(v)1.1 dysfunction on motor axons in vivo. The median nerve was stimulated at the wrist and compound muscle action potentials were recorded from abductor pollicis brevis. Threshold tracking techniques were used to record strength-duration time constant, threshold electrotonus, current/threshold relationship and the recovery cycle. Recordings from 20 patients from eight kindreds with different KCNA1 point mutations were compared with those from 30 normal controls. All 20 patients had a history of episodic ataxia and 19 had neuromyotonia. All patients had similar, distinctive abnormalities: superexcitability was on average 100% higher in the patients than in controls (P < 0.00001) and, in threshold electrotonus, the increase in excitability due to a depolarizing current (20% of threshold) was 31% higher (P < 0.00001). Using these two parameters, the patients with episodic ataxia type 1 and controls could be clearly separated into two non-overlapping groups. Differences between the different KCNA1 mutations were not statistically significant. Studies of nerve excitability can identify K(v)1.1 dysfunction in patients with episodic ataxia type 1. The simple 15 min test may be useful in diagnosis, since it can differentiate patients with episodic ataxia type 1 from normal controls with high sensitivity and specificity.
%Z FOR Codes: 110903 111603


%0 Journal Article
%~ PubMed
%A Ng, K
%A Winter, S
%A Sue, C
%A Burke, D
%T Preserved motor axonal membrane potential in mitochondrial disease.
%B Journal of Neurology, Neurosurgery, and Psychiatry
%D 2010
%C United Kingdom
%I BMJ Group
%V 81
%N 8
%P 844-846
%@ 1468-330X
%X Mitochondrial disorders are characterised by protean neurological manifestations including peripheral neuropathy. The neuropathy is typically an axonal process, with a proposed mechanism being degradation of the membrane potential of the axon due to dysfunction of energy-dependent Na(+)/K(+) ATPase pump. To address this issue, we studied the excitability of motor axons in the median nerve in 16 individuals identified with gene testing or muscle biopsy. Twelve patients had clinical or nerve conduction abnormalities. Strength--duration time constant, threshold electrotonus, current--threshold relationship and recovery cycle were identical to control values. These findings imply that an alternative mechanism to a change in membrane potential is responsible for neuronal injury in these patients.
%Z FOR Codes: 110905 111603


%0 Journal Article
%~ PubMed
%A Trevillion, Louise
%A Howells, James
%A Bostock, Hugh
%A Burke, David
%T Properties of Low-Threshold Motor Axons in the Human Median Nerve.
%B Journal of Physiology
%D 2010
%C United Kingdom
%I Wiley-Blackwell Publishing Ltd.
%V 588
%N 13
%P 2503-2515
%@ 1469-7793
%X This study investigated the excitability and accommodative properties of low-threshold human motor axons to test whether these motor axons have greater expression of the persistent Na(+) conductance, I(NaP). Computer-controlled threshold tracking was used to study 22 single motor units and the data were compared with compound motor potentials of various amplitudes recorded in the same experimental session. Detailed comparisons were made between the single units and compound potentials that were 40% or 5% of maximal amplitude, the former because this is the compound potential size used in most threshold tracking studies of axonal excitability, the latter because this is the compound potential most likely to be composed entirely of motor axons with low thresholds to electrical recruitment. Measurements were made of the strength-duration relationship, threshold electrotonus, current-voltage relationship, recovery cycle and latent addition. The findings did not support a difference in I(NaP). Instead they pointed to greater activity of the hyperpolarization-activated inwardly rectifying current (I(h)) as the basis for low threshold to electrical recruitment in human motor axons. Computer modelling confirmed this finding, with a doubling of the hyperpolarization-activated conductance proving the best single parameter adjustment to fit the experimental data. We suggest that the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel(s) expressed on human motor axons may be active at rest and contribute to resting membrane potential.
%Z FOR Codes: 111603 110905


%0 Journal Article
%~ PubMed
%A Burke, David
%T Whither needle EMG?
%B Clinical Neurophysiology
%D 2010
%C Ireland
%I Elsevier Ireland Ltd
%V 121
%N 9
%P 1373-1375
%@ 1872-8952
%X 
%Z FOR Codes: 111603 110904


%0 Journal Article
%~ PubMed
%A Jankelowitz, Stacey
%A Mohamed, Armin
%A Burke, David
%T Axonal effects of camphor poisoning.
%B Journal of Clinical Neuroscience
%D 2009
%C United Kingdom
%I Churchill Livingstone
%V 16
%N 12
%P 1639-1641
%@ 0967-5868
%X This report documents changes to axonal excitability in motor nerves in acute camphor toxicity. Although there were no changes to indicate an alteration in resting membrane potential, there was an exaggerated response to hyperpolarising currents in both threshold electrotonus and the current-threshold relationship. These findings suggest a transient decrease in the hyperpolarisation-activated conductance (I(H)). This report demonstrates that recently developed techniques for measuring axonal excitability are readily applied in the acute care setting and can document subclinical abnormalities that could be relevant to the underlying pathophysiology.
%Z FOR Codes: 1109


%0 Journal Article
%~ PubMed
%A Jankelowitz, S K
%A Burke, David
%T Axonal excitability in the forearm: Normal data and differences along the median nerve.
%B Clinical Neurophysiology
%D 2009
%C Ireland
%I Elsevier Ireland Ltd
%V 120
%N 1
%P 167-173
%@ 1388-2457
%X This study was designed to validate excitability studies of motor axons in the median nerve at the elbow, innervating forearm muscles (flexor carpi radialis, FCR) and collect normal data for this stimulation site. The differences in measures of excitability due to different sites of stimulation or a different test muscle group was also determined.
%Z FOR Codes: 110905 111603


%0 Journal Article
%~ PubMed
%A Tomlinson, Susan E
%A Hanna, Michael G
%A Kullmann, Dimitri M
%A Tan, S Veronica
%A Burke, David
%T Clinical neurophysiology of the episodic ataxias: insights into ion channel dysfunction in vivo.
%B Clinical Neurophysiology
%D 2009
%C Ireland
%I Elsevier Ireland Ltd
%V 120
%N 10
%P 1768-1776
%@ 1872-8952
%X Clinical neurophysiology has become an invaluable tool in the diagnosis of muscle channelopathies, but the situation is less clear cut with neuronal channelopathies. The genetic episodic ataxias are a group of disorders with heterogeneous phenotype and genotype, but share in common the feature of intermittent cerebellar dysfunction. Episodic ataxia (EA) types 1 and 2 are the most widely recognised of the autosomal dominant episodic ataxias and are caused by dysfunction of neuronal voltage-gated ion channels. There are central and peripheral nervous system manifestations in both conditions, and they are therefore good models of neuronal channelopathies to study neurophysiologically. To date most work has focussed upon characterising the electrophysiological properties of mutant channels in vitro. This review summarises the role of voltage-gated potassium and calcium channels, mutations of which underlie the main types of episodic ataxia types 1 and 2. The clinical, genetic and electrophysiological features of EA1 and EA2 are outlined, and a protocol for the assessment of these patients is proposed.
%Z FOR Codes: 110905


%0 Journal Article
%~ PubMed
%A Burke, David
%A Jankelowitz, Stacey K
%T Fatigue in chronic inflammatory demyelinating polyneuropathy.
%B Muscle & Nerve
%D 2009
%C United States
%I John Wiley & Sons, Inc.
%V 39
%N 5
%P 713-714
%@ 1097-4598
%X 
%Z FOR Codes: 110905


%0 Journal Article
%~ PubMed
%A Tomlinson, Susan
%A Burke, David
%A Hanna, Mike
%A Koltzenburg, Martin
%A Bostock, Hugh
%T In vivo assessment of HCN channel current (I(h)) in human motor axons.
%B Muscle & Nerve
%D 2009
%C United States
%I John Wiley & Sons, Inc.
%V 41
%N 2
%P 247-256
%@ 0148-639X
%X The "Trond" protocol of nerve excitability tests has been used widely to assess axonal function in peripheral nerve. In this study, the routine Trond protocol was expanded to refine assessment of cAMP-dependent, hyperpolarization-activated current (I(h)) activity. I(h) activity is generated by hyperpolarization-activated, cyclic nucleotide-modulated (HCN) channels in response to hyperpolarization. It limits activity-dependent hyperpolarization, contributes to neuronal automaticity, and is implicated in chronic pain states. Published data regarding I(h) activity in motor nerve are scant. We used additional strong, prolonged hyperpolarizing conditioning stimuli in the threshold electrotonus component of the Trond protocol to demonstrate the time-course of activation of I(h) in motor axons. Fifteen healthy volunteers were tested on four occasions during 1 week. I(h) action was revealed in the threshold electrotonus by the limiting and often reversal, after about 100 ms, of the threshold increase caused by strong hyperpolarizing currents. Statistical analysis by repeated-measures analysis of variance enabled confidence limits to be established for variation between subjects and within subjects. The results demonstrate that, of all the excitability parameters, those dependent on I(h) were the most characteristic of an individual, because variance between subjects was more than four times the variance within subjects. This study demonstrates a reliable method for in vivo assessment of I(h,) and also serves to document the normal variability in nerve excitability properties within subjects.
%Z FOR Codes: 1109


%0 Journal Article
%~ PubMed
%A Vucic, Steve
%A Cheah, Benjamin C
%A Krishnan, Arun V
%A Burke, David
%A Kiernan, Matthew C
%T The effects of alterations in conditioning stimulus intensity on short interval intracortical inhibition.
%B Brain Research
%D 2009
%C Netherlands
%I Elsevier Science Bv
%V 1273
%N 
%P 39-47
%@ 0006-8993
%X Short interval intracortical inhibition [SICI] is mediated by cortical inhibitory interneurons, with two physiologically distinct phases at interstimulus interval [ISI]<1 ms and 2.5-3 ms. The second phase of SICI is mediated by synaptic mechanisms, while the first phase has been attributed to axonal refractoriness, synaptic mechanisms or both. In the present study, threshold-tracking transcranial magnetic stimulation was used to explore mechanisms underlying SICI. SICI was studied in 10 normal subjects at three different conditioning stimulus [CS] intensities [40%, 70% and 90% of resting motor threshold, RMT, defined as the threshold for a MEP of approximately 0.2 mV]. Motor responses were recorded from abductor pollicis brevis. Maximal SICI developed with CS set to 70% RMT [SICI(70%)], with two phases evident, at ISI 1 ms [12.7+/-3.4%] and ISI 2.5 ms [19.3+/-2.9%]. With CS set to 40% RMT, SICI occurred between 1 ms and 5 ms, peaking at 2.5 ms and was reduced [1.9+/-1.4%, P<0.0001] compared to peak SICI(70%). The small SICI peak at 1 ms was absent. With CS at 90% RMT, SICI developed between 2 and 5 ms, peaking at 4 ms [11.2+/-7.8%]. Facilitation was evident at 1 ms. The findings from the present study suggest that inhibitory circuits with different thresholds underlie the phases of SICI, with synaptic mechanisms also critical to the development of SICI at 1 ms.
%Z FOR Codes: 111603 110903 110603


%0 Journal Article
%~ PubMed
%A Burke, David
%A Howells, James
%A Trevillion, Louise
%A McNulty, Penelope A
%A Jankelowitz, Stacey K
%A Kiernan, Matthew C
%T Threshold behaviour of human axons explored using subthreshold perturbations to membrane potential.
%B Journal of Physiology
%D 2009
%C United Kingdom
%I Blackwell Publishing Ltd.
%V 587
%N Pt 2
%P 491-504
%@ 0022-3751
%X The present study explores the threshold behaviour of human axons and the mechanisms contributing to this behaviour. The changes in excitability of cutaneous afferents in the median nerve at the wrist were recorded to a long-lasting subthreshold conditioning stimulus, with a waveform designed to maximize the contribution of currents active in the just-subthreshold region. The conditioning stimulus produced a decrease in threshold that developed over 3-5 ms following the end of the depolarization and then decayed slowly, in a pattern similar to the recovery of axonal excitability following a discharge. To ensure that the conditioning stimulus did not activate low-threshold axons, similar recordings were then made from single motor axons in the ulnar nerve at the elbow. The findings were comparable, and behaviour with the same pattern and time course could be reproduced by subthreshold stimuli in a model of the human axon. In motor axons, subthreshold depolarizing stimuli, 1 ms long, produced a similar increase in excitability, but the late hyperpolarizing deflection was less prominent. This behaviour was again reproduced by the model axon and could be explained by the passive properties of the nodal membrane and conventional Na+ and K+ currents. The modelling studies emphasized the importance of leak current through the Barrett-Barrett resistance, even in the subthreshold region, and suggested a significant contribution of K+ currents to the threshold behaviour of axons. While the gating of slow K+ channels is slow, the resultant current may not be slow if there are substantial changes in membrane potential. By extrapolation, we suggest that, when human axons discharge, nodal slow K+ currents will be activated sufficiently early to contribute to the early changes in excitability following the action potential.
%Z FOR Codes: 111603 110905


%0 Journal Article
%~ PubMed
%A McNulty, Penelope A
%A Burke, David
%T When cold becomes hot.
%B Journal of Physiology
%D 2009
%C United Kingdom
%I Wiley-Blackwell Publishing Ltd.
%V 587
%N Pt 23
%P 5511
%@ 1469-7793
%X 
%Z FOR Codes: 1109 606 1116


%0 Journal Article
%~ PubMed
%A Uysal, Hilmi
%A Larsson, Lars-Erik
%A Efendi, Hüsnü
%A Burke, David
%A Ertekin, Cumhur
%T Medium-latency reflex response of soleus elicited by peroneal nerve stimulation.
%B Experimental Brain Research
%D 2008
%C Germany
%I Springer
%V 193
%N 2
%P 275-286
%@ 1432-1106
%X A medium-latency response (MLR) has been recorded from soleus during stance and walking, and has been attributed to stretch-evoked volleys in group II afferents. The present paper describes a MLR in soleus evoked by stimulating the deep peroneal nerve, documents its characteristics and addresses its likely origin. The MLR of soleus was recorded in healthy subjects and hemiplegic patients, following electrical stimulation of the deep peroneal nerve at the fibula at rest, during voluntary dorsiflexion, during plantar flexion, during external restraint to the ankle dorsiflexion movement, during limb cooling, during limb ischaemia and 1 h after the ingestion of tizanidine. The dorsiflexion movement of the foot was measured using an accelerometer. During cooling, ischaemia and after tizanidine, changes in the MLR were compared with changes in the soleus H reflex, Achilles tendon reflex and, during cooling, F waves of abductor hallucis. The MLR was facilitated by voluntary dorsiflexion, was suppressed during plantar flexion, disappeared when ankle movement was prevented, and was enhanced in patients with spastic hemiplegia. Cooling delayed the MLR significantly more than the Achilles tendon reflex and the abductor hallucis F wave. During ischaemia the response was significantly less affected than the Achilles tendon reflex and the soleus H reflex. Tizanidine suppressed the MLR, but not the soleus H and tendon reflexes. The latencies and the experiments using cooling, ischaemia and tizanidine implicate soleus group II afferents in the genesis of this response.
%Z FOR Codes: 110903 111603 1106


%0 Journal Article
%~ PubMed
%A McNulty, Penelope A
%A Jankelowitz, Stacey Kyle
%A Wiendels, Tanya M
%A Burke, David
%T Post-activation depression of the soleus H reflex measured using threshold tracking.
%B Journal of Neurophysiology
%D 2008
%C United States
%I American Physiological Society
%V 100
%N 6
%P 3275-3284
%@ 0022-3077
%X The interpretation of changes in the soleus H reflex is problematic in the face of reflex gain changes, a nonlinear input/output relationship for the motoneuron pool, and a nonhomogeneous response of different motoneurons to afferent inputs. By altering the stimulus intensity to maintain a constant reflex output, threshold tracking allows a relatively constant population of alpha-motoneurons to be studied. This approach was used to examine postactivation ("homosynaptic") depression of the H reflex (HD) in 23 neurologically healthy subjects. The H reflex was elicited by tibial nerve stimulation at 0.05, 0.1, 0.3, 1, and 2 Hz at rest and during voluntary plantar flexion at 2.5, 5, and 10% of maximum. A computerized threshold tracking procedure was used to set the current needed to generate a target H reflex 10% of M(max). The current needed to produce the target reflex increased with stimulus rate but not significantly beyond 1 Hz. In three subjects, the current needed to produce H reflexes of 5, 10, 15, and 20% M(max) at 0.3, 1, and 2 Hz increased with rate and with the size of the test H reflex. HD was significantly reduced during voluntary contractions. Using threshold tracking, HD was maximal at lower frequencies than previously emphasized, probably because HD is greater the larger the test H reflex. This would reinforce the greater sensitivity of small motoneurons to reflex inputs.
%Z FOR Codes: 110903 111603 110603


%0 Book Section
%A Burke, David
%T Recording MEPs to transcranial electrical stimulation and SEPs to peripheral nerve stimulation simultaneously from the spinal cord
%B Handbook of Clinical Neurophysiology: Intraoperative Monitoring of Neural Function, 8
%D 2008
%C Netherlands
%I Elsevier
%V 
%N 
%P 252-259
%@ 978-0-444-51824-8
%E Nuwer, Marc R
%X 
%Z FOR Codes: 1109


%0 Journal Article
%A Burke, David
%T Revolution and evolution in science and scientific publishing
%B Clinical Neurophysiology
%D 2008
%C Ireland
%I Elsevier
%V 119
%N 1
%P 1
%@ 1388-2457
%X 
%Z FOR Codes: 1109


%0 Journal Article
%~ PubMed
%A Ng, Karl
%A Howells, James
%A Pollard, John D
%A Burke, David
%T Up-regulation of slow K+ channels in peripheral motor axons: a transcriptional channelopathy in multiple sclerosis.
%B Brain
%D 2008
%C United Kingdom
%I Oxford University Press
%V 131
%N Pt 11
%P 3062-3071
%@ 1460-2156
%X Spinal lesions produce plastic changes in motoneuron properties. We have documented the excitability of motor axons in the median nerve of 12 patients with multiple sclerosis and 50 normal subjects, hypothesizing that plastic changes in the properties of spinal motoneurons might be reflected in the properties of peripheral motor axons and be demonstrable in vivo. In the patients, there were changes in physiological measures of axonal excitability attributable to increased slow K(+) channel activity. Other measures were within control limits. These changes could be modelled by an 11% increase in slow K(+) current, with compensatory changes in membrane potential, suggesting increased expression of the responsible channels. The changes cannot be explained solely by changes in membrane potential and are not those expected if peripheral nerve axons were involved in the inflammatory process of multiple sclerosis. They probably represent a transcriptional channelopathy, due to up-regulation of channel expression. The abnormalities do not imply that peripheral nerve function has been significantly compromised, but they do suggest that the properties of the parent motoneurons have changed. This study thus provides evidence for plasticity in motoneuronal properties at a molecular level, the first such evidence for intact human subjects.
%Z FOR Codes: 1109 1116


%0 Journal Article
%~ PubMed
%A Jankelowitz, S K
%A McNulty, P A
%A Burke, David
%T Changes in measures of motor axon excitability with age.
%B Clinical Neurophysiology
%D 2007
%C Ireland
%I Elsevier Ireland Ltd
%V 118
%N 6
%P 1397-1404
%@ 1388-2457
%X OBJECTIVE: Threshold tracking is a novel technique that permits examination of the excitability of human axons in vivo. Protocols have been validated for sensory and motor axons, but there are limited data on the changes in the excitability of motor axons with age. This study aimed to determine such changes from the third to the eighth decades. METHODS: Sixty healthy subjects aged 22-79, 10 per decade, were studied using the TRONDXM4 protocol of the QTRAC threshold-tracking program to assess motor axon function. The median nerve was stimulated at the wrist and the compound muscle action potential was recorded from the thenar muscles. RESULTS: There was an increase in threshold in elderly subjects, associated with a decrease in slope of the stimulus-response curves. Strength-duration time constant and threshold electrotonus to depolarising and hyperpolarising currents of up to 40% did not change significantly with aging. The current-threshold relationship was similar across all decades for subthreshold depolarising currents, but the slope of the current-threshold relationship was significantly steeper the older the subjects for hyperpolarising currents, particularly those greater than 40% of threshold. There was also a significant decrease in supernormality in the recovery cycle with increasing age. CONCLUSIONS: The threshold of axons increases with age and the extent of supernormality decreases. There may also be greater inward rectification in motor axons, perhaps due to greater activity of I(H), the hyperpolarisation-activated conductance, though this is only significant with hyperpolarising currents greater than 40% of the threshold current. SIGNIFICANCE: Many indices of axonal excitability, such as strength-duration time constant, the relative refractory period, late subnormality, threshold electrotonus and the depolarising side of the current-threshold relationship, do not change significantly with age. For other indices, age-related changes may be due to a combination of non-neural factors that alter current access to the node of Ranvier, changes in the axon and its myelination and, possibly, changes in channel activity and/or changes in extracellular [K(+)](o).
%Z FOR Codes: 110905


%0 Book Section
%A Vucic, Ostoja (Steve)
%A Burke, David
%A Kiernan, Matthew C
%T Diagnosis of motor neurone disease
%B The Motor Neurone Disease Handbook
%D 2007
%C Australia
%I Australasian Med Publ Co Ltd
%V 
%N 
%P 89-104
%@ 9780977578634
%E Kiernan, Matthew
%X 
%Z FOR Codes:


%0 Journal Article
%~ PubMed
%A Burke, David
%A Howells, James
%A Trevillion, Louise
%A Kiernan, Matthew C
%A Bostock, Hugh
%T Inflections in threshold electrotonus to depolarizing currents in sensory axons.
%B Muscle & Nerve
%D 2007
%C United States
%I Elsevier Science Inc
%V 36
%N 6
%P 849-852
%@ 1097-4598
%X Threshold electrotonus involves tracking the changes in axonal excitability produced by subthreshold polarizing currents and is the only technique that allows insight into the function of internodal conductances in human subjects in vivo. There is often an abrupt transient reversal of the threshold change as excitability increases in response to conditioning depolarizing currents (S1 phase). In recordings from motor axons, it has been recently demonstrated that this notch or inflection is due to activation of low-threshold axons. We report that a notch is frequently seen in sensory recordings (in 33 of 50 healthy subjects) using the standard threshold electrotonus protocol. When large, the notch can distort subsequent phases of threshold electrotonus and could complicate quantitative measurements and modeling studies.
%Z FOR Codes: 110905 111603


%0 Journal Article
%A Ng, Karl
%A Burke, David
%T Nerve Excitability Studies in the Present Era
%B Advances in Clinical Neuroscience & Rehabilitation
%D 2007
%C United Kingdom
%I Whitehouse Publishing
%V 7
%N 5
%P 29-30
%@ 1473-9348
%X 
%Z FOR Codes: 1109


%0 Journal Article
%~ PubMed
%A Trevillion, Louise
%A Howells, James
%A Burke, David
%T Outwardly rectifying deflections in threshold electrotonus due to K+ conductances.
%B Journal of Physiology
%D 2007
%C United Kingdom
%I Blackwell Publishing Ltd.
%V 580
%N Pt 2
%P 685-696
%@ 0022-3751
%X A transient decrease in excitability occurs regularly during the S1 phase of threshold electrotonus to depolarizing conditioning stimuli for sensory and, less frequently, motor axons. This has been attributed to the outwardly rectifying action of fast K(+) channels, at least in patients with demyelinating diseases. This study investigates the genesis of this notch in healthy axons. Threshold electrotonus was recorded for sensory and motor axons in the median nerve at the wrist in response to test stimuli of different width. The notch occurred more frequently the briefer the test stimulus, and more frequently in sensory studies. In studies on motor axons, the notch decreased in latency and increased in amplitude as the conditioning stimulus increased or the limb was cooled. Low-threshold axons displayed profound changes in strength-duration time constant even though the threshold electrotonus curves contained no detectable notch. When a 1.0 ms current was added to subthreshold conditioning stimuli to trigger EMG, the notch varied with the timing and intensity of the brief current pulse. This study finds no evidence for an outwardly rectifying deflection due to K(+) channels, other than the slow accommodation attributable to slow K(+) currents. In normal motor axons, a depolarization-induced notch during the S1 phase of threshold electrotonus is the result of the conditioning stimulus exceeding threshold for some axons. The notch is more apparent in sensory axons probably because of the lower slope of the stimulus-response curve and their longer strength-duration time constant rather than a difference in K(+) conductances. This may also explain the notch in demyelinating diseases.
%Z FOR Codes: 110905


%0 Journal Article
%~ PubMed
%A Jankelowitz, Stacey K
%A Howells, James
%A Burke, David
%T Plasticity of inwardly rectifying conductances following a corticospinal lesion in human subjects.
%B Journal of Physiology
%D 2007
%C United Kingdom
%I Blackwell Publishing Ltd.
%V 581
%N Pt 3
%P 927-940
%@ 0022-3751
%X This study investigated whether there are changes in the excitability of motor axons in peripheral nerves of patients with corticospinal lesions, reflecting plasticity of the motoneuron due to altered descending drives and/or changes in afferent feedback. The excitability of motor and sensory axons in peripheral nerves of the affected limb of 11 patients with unilateral hemiparesis due to stroke was compared with that for the unaffected limbs and with data for 12 age-matched controls. There was significantly less accommodation to hyperpolarizing currents in motor axons on the affected side. There were small differences between the data for the unaffected side and that of the control subjects but these were not statistically significant. Other findings indicate that there was no change in resting membrane potential. There was no comparable alteration in the excitability of sensory axons. The changes in response of motor axons to hyperpolarizing currents could be reproduced in a computer model of the human motor axon by reducing the hyperpolarization-activated conductance, I(H), by 30% and the quantitatively small leak conductance by 77%. The data for the uninvolved side matched the data for control subjects best when I(H) was increased. These findings are consistent with modulation of I(H) by activity. They demonstrate a change in the biophysical properties of motor axons not directly affected by the pathology and synaptically remote from the lesion, and have implications for ''trans-synaptic'' changes in central nervous system pathways. In human subjects studies of motor axon properties may allow insight into processes affecting the motoneuron.
%Z FOR Codes: 110903 110905 111603


%0 Journal Article
%~ PubMed
%A Iglesias, Caroline
%A Marchand-Pauvert, Veronique
%A Lourenço, George
%A Burke, David
%A Pierrot-Deseilligny, Emmanuel
%T Task-related changes in propriospinal excitation from hand muscles to human flexor carpi radialis motoneurones.
%B Journal of Physiology
%D 2007
%C United Kingdom
%I Blackwell Publishing Ltd.
%V 582
%N Pt 3
%P 1361-1379
%@ 0022-3751
%X This study addresses whether there is excitation from human hand muscles to flexor carpi radialis (FCR) motoneurones mediated through propriospinal circuits and, if so, whether it is used in specific motor tasks. Electrical stimuli to the ulnar nerve at wrist level produced an excitation in FCR motoneurones with characteristics typical of a propriospinally mediated effect: low threshold (0.6 x motor threshold (MT)), a group I effect that was not reproduced by purely cutaneous stimuli, long central delay (4.1 +/- 0.4 ms in single units), suppression when the stimulus intensity was increased, and facilitation of the corticospinal excitation at the premotoneuronal level. Ulnar-induced propriospinally mediated excitation was compared during selective voluntary contractions of the FCR and, at equivalent level of FCR EMG, during tasks in which the FCR was activated automatically in postural contractions rather than voluntarily (grip, pinching and pointing). The excitation was significantly greater during grip (and pinching) than during voluntary FCR contractions and pointing, whether measured in single motor units or tonic EMG activity, or whether the response to motor cortex stimulation was assessed as the compound motor-evoked potential or the corticospinal peak in single units. The discrepancy between the tasks appeared with ulnar intensities above 0.8 x MT and was then present across a wide range of stimulus intensities. This suggests a reduction in the corticospinal control of ''feedback inhibitory interneurones'' mediating peripheral inhibition to propriospinal neurones during grip and pinching. The resulting more effective background excitation of propriospinal neurones by the peripheral input from hand muscles could contribute to stabilizing the wrist during grip.
%Z FOR Codes: 110904