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Introduction Patients diagnosed with amyotrophic lateral sclerosis (ALS) generally have a limited medical history and a normal body mass index, raising the possibility of a premorbid ALS phenotype. Methods The prevalence of cardiometabolic factors was analyzed in 58 ALS patients via comprehensive cardiovascular assessments and compared with Australian population norms. Results ALS patients had good cardiac fitness and no reported cardiovascular events. Average blood pressure, heart rate, PR interval, and corrected QT interval were in the normal range. There were significantly fewer obese women in the ALS cohort (13.6%, P

Patients with hereditary neuropathy with liability to pressure palsies (HNPP) manifest with episodes of focal paresis when exposed to mechanical stress, although the basis for vulnerability to conduction block remains relatively unexplained.Axonal excitability techniques were utilized to provide insights into pathophysiological mechanisms in 13 HNPP patients, stimulating median motor and sensory axons at the wrist.In HNPP, distal latencies were prolonged, and motor and sensory amplitudes were reduced. Threshold was increased. Depolarizing and hyperpolarizing electrotonus was greater, and resting current-threshold slope was reduced. There were greater threshold changes in superexcitability, and refractoriness was decreased.Taken together, excitability testing in patients with HNPP established axonal hyperpolarization in both motor and sensory axons that may be attributable to changes in nerve architecture. In turn, the hyperpolarized resting membrane potential in HNPP may be a major predisposing factor for development of conduction block with mechanical stresses.

Maladaptive plasticity involving the unaffected hemisphere (UH) in stroke patients may contribute to post-stroke deficits, including spasticity. We investigated the central and peripheral effects of botulinum toxin in post-stroke spasticity to determine whether there is modulation of cortical processes in the UH.Transcranial magnetic stimulation and peripheral nerve excitability studies were undertaken in 5 stroke patients with upper limb spasticity before (T1) and 6 weeks after (T2) botulinum injection.Transcranial magnetic stimulation demonstrated inexcitable motor cortices of the affected hemisphere at T1 and T2, and short-interval intracortical inhibition (SICI) in the UH was significantly reduced at T1. At T2, SICI in the UH increased significantly compared with T1, normalizing to controls, and was found to be associated with clinical improvements in spasticity. Peripheral excitability parameters were unchanged after injection.Cortical excitability changes were demonstrated in UH, suggesting that the clinical benefits of botulinum toxin relate to modulation of abnormal central reorganization (maladaptive plasticity) in post-stroke spasticity.

The mechanisms of lead neuropathy remain unexplained. A 48-year-old painter presented after undertaking a 3-week project of paint removal without the use of a protective mask. Two weeks later, he developed fasciculations, weakness, and muscle wasting. Nerve conduction studies demonstrated a motor neuropathy. A high serum lead level was identified, leading to a diagnosis of acute lead neuropathy.To investigate the pathophysiology, nerve excitability studies were undertaken acutely and in convalescence. Studies were undertaken at baseline and after the induction of limb ischemia.Prominent abnormalities of excitability were noted, including a rightward shift of stimulus-response curves, reduction in depolarizing threshold electrotonus, and increased refractoriness. These changes became more severe with limb ischemia, and there was abolition of the superexcitable period and increased refractoriness.We identified prominent changes in nerve excitability in lead neuropathy. The results suggest that there is impairment of axonal energy-dependent processes in lead neuropathy.

In this study we investigated the changes in axonal excitability and the generation of neurological symptoms in response to focal nerve compression (FNC) of the median nerve in carpal tunnel syndrome (CTS).Sensory excitability recordings were undertaken in 11 CTS patients with FNC being applied at the wrist using a custom-designed electrode.During FNC, refractoriness increased significantly (62.4 ± 3.4%; P0.001), associated with a rapid reduction in superexcitability (16.9 ± 2.8%; P0.001) and sensory nerve action potential amplitude (SNAP) (32.4 ± 3.9%; P0.001), consistent with axonal depolarization. Associated with these changes, paresthesiae steadily increased throughout FNC, as did numbness. Reductions in SNAP amplitude and superexcitability developed more rapidly for CTS patients during FNC compared with controls, and these changes were associated with more marked symptoms.Axonal responses to compression are impaired in CTS. This may suggest a greater reliance on axonal membrane Na(+) /K(+) -ATPase function.

Neuropathic diseases typically begin distally and spread proximally. Irrespective of the etiology, pathological investigations often indicate changes consistent with ischemia. In the present study, threshold tracking was used to investigate length-dependent differences in ischemic susceptibility of lower-limb axons in 6 healthy volunteers, with ischemia induced by a sphygmomanometer cuff inflated to 200 mm Hg and maintained for 13 minutes. Following stimulation of the peroneal nerve at the fibula neck, compound muscle action potentials were recorded proximally from tibialis anterior (TA) and distally from extensor digitorum brevis (EDB). During ischemia, excitability changes were consistent with nerve depolarization, with a greater reduction in threshold in EDB than TA. This reduction in threshold was associated with an increase in refractoriness, decrease in superexcitability, and prolongation of strength-duration time constant, consistent with axonal depolarization. With release of ischemia, reversal of these changes was associated with an increase in threshold, greater in EDB than TA, indicating axonal hyperpolarization. The rate of recovery of threshold was similar proximally and distally, arguing against a gradient in Na(+)/K(+) pump function along the peroneal nerve. The greater changes in threshold in EDB during and after ischemia suggest an increased susceptibility of more distal axons to ischemia and are likely to contribute to the length-dependent development of neuropathy.

For three motoneuron pools that differ in excitability to Ia inputs [tibialis anterior (TA), abductor pollicis brevis (APB), and soleus], F-wave parameters were measured at rest, during voluntary contraction, and following prolonged vibration. There was an inverse relationship between F-wave chronodispersion and F-wave persistence at rest, and this appeared to be related to the ease of recording the H reflex for the motoneuron pool. During a steady voluntary contraction, overall F-wave activity increased in amplitude but decreased in duration for TA and APB. Following vibration of the test muscle at 50 HZ for 10 min there was a long-lasting depression of the H reflexes of TA and APB, but no significant change in F-wave measurements. These findings are consistent with the view that reflex discharges can prevent F waves in low-threshold motor units, and that chronodispersion is affected by the extent of reflex activity; that is, chronodispersion and related F-wave measurements do not measure motor properties exclusively. The findings also suggest that F waves provide a flawed measure of the excitability of the motoneuron pool.

The clinical and neurophysiological features of multifocal motor neuropathy (MMN) indicate selective involvement of motor axons, but pathological abnormalities in sensory axons suggest a more widespread disease process. The present study was undertaken to determine whether the focal abnormalities are associated with widespread subclinical abnormalities in motor axons. Threshold tracking was used to measure excitability properties (stimulus-response curves, strength-duration properties, recovery cycle, and threshold electrotonus) of the median nerve in five patients with MMN with lesions proximal to the site of testing. Patients were compared with 25 healthy controls. The changes in excitability indices were similar to those in controls, and in one patient there was no alteration after treatment with intravenous gammaglobulin. In this patient, indices of axonal excitability were also measured before, during, and after ischemia of the arm for 10 min. Again no differences were detected. This study provides no evidence for a generalized subclinical abnormality in MMN, at least when disease duration is less than 6 years.

To investigate whether there are inter-nerve differences in the extent and pattern of axonal excitability changes produced by voluntary contractions of tibialis anterior (TA) and abductor pollicis brevis (APB), threshold tracking was used to measure axonal excitability parameters [threshold, supernormality and strength-duration time constant (τSD)] of peroneal and median motor axons in 11 healthy subjects. Maximal contractions for 1 min resulted in an increase in threshold, an increase in supernormality, a decrease in τSD and an increase in latency, all of which indicate axonal hyperpolarization. The increase in threshold was less in peroneal axons (18 ± 4%) than median axons (37 ± 6%, mean ± SEM, P < 0.001), and was accompanied by smaller absolute changes in latency, supernormality, and τSD. Peroneal axons had less supernormality at rest but a greater change in supernormality for the change in threshold. There were major contraction-induced changes in the compound muscle action potential of TA but not that of APB. Voluntary contractions depress axonal excitability, but the changes are quantitatively different for motor axons innervating different muscles. There are three clinical implications. First, weakness and fatigue due to activity-dependent conduction block may vary for different muscles, independent of disease severity, and therapeutic strategies to overcome activity-dependent conduction block may not be equally effective for different muscles. Second, in motor control studies using the H reflex to document motoneuron excitability, a constant stimulus will not produce a constant neural volley if the stimulated axons have been activated by, for example, a voluntary contraction. Third, TA is probably not optimal for testing for activity-dependent conduction block. © 2002 John Wiley & Sons, Inc. Muscle Nerve 25: 176–184, 2002 DOI 10.1002/mus.10030

Recent evidence suggests that two conductances responsible for accommodation to changes in membrane potential (a slow K(+) conductance and inward rectification [I(H)]) are less active on cutaneous afferents in the sural nerve than on those in the median nerve, and it has been suggested that these axons would therefore respond differently to stress, whether natural or due to disease. The present study was undertaken in eight healthy volunteers to determine whether these afferents respond differently to the depolarizing and hyperpolarizing stresses that accompany ischemia for 13 min and subsequent recovery. During ischemia, the decrease in threshold was quantitatively less for the sural afferents, as were the changes in the other indices of axonal excitability, presumably because the ischemic depolarization was less for sural afferents. Following release of ischemia, there was, as predicted, a divergence in the pattern of threshold change. With median afferents there was evidence of a transient depolarization, believed to be due to inward rectification, superimposed on a long-lasting hyperpolarization. The response of sural afferents lacked this transient depolarizing threshold change. Cutaneous afferents in the median and sural nerves behave differently in response to ischemic and postischemic stresses, and it is likely that they will also respond differently to disease processes. In a number of respects the differences between sural and median afferents are analogous to differences between diabetic and normal nerves.

In acquired polyneuropathies, symptoms and signs are typically distal and symmetrical, more prominent in the lower limbs than the upper limbs. This study was undertaken to measure the extent of the decrease in excitability produced by single impulses and by impulse trains in cutaneous afferents in the median and sural nerves, and to compare the resulting changes in excitability of these afferents. Threshold tracking was used in 10 healthy subjects to measure the changes in threshold for a compound sensory action potential of 50% maximum produced by conditioning stimuli. Following a single supramaximal conditioning stimulus, the threshold changes occurring during the refractory and supernormal periods were identical for the two nerves, but there was a greater increase in threshold during the late subnormal period for median afferents. Following a train of 10 supramaximal conditioning stimuli, threshold increased by approximately 40% for median afferents and by approximately 20% for sural afferents. These differences are consistent with differences in a slow K(+) conductance. It is suggested that the hypo-excitability produced by brief trains of impulses may be sufficient to disturb conduction in diseased nerve fibers, and that the lesser expression of slow K(+) conductances on cutaneous afferents in the sural nerve could render them more sensitive to depolarizing stresses than median afferents. This could be a factor in the ease with which sural afferents become ectopically active in polyneuropathies.