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Biomedical subjects

K R Mills

Publications and source records attributed to K R Mills.

At least 37 records · Page 2Linked to original sources
PubMed1999

Strength-duration properties of peripheral nerve in acquired neuromyotonia.

The strength-duration time constant (SDTC) of a myelinated axon is a property of the nodal membrane and is sensitive to changes in membrane potential. Strength-duration time constants for motor axons and cutaneous afferents of the median nerve were measured in 9 patients with acquired neuromyotonia (NMT), a condition of peripheral nerve hyperexcitability, and 15 control patients. Mean motor axon time constants were significantly prolonged (344 +/- 100 micros) in patients compared to healthy controls (264 +/- 34 micros; P = 0.038), but sensory axon time constants were not significantly different. Motor axon time constants were longer than sensory axon time constants in 4 of the patients with neuromyotonia, suggesting that the nodal membrane was depolarized by an ectopic focus at the site of nerve stimulation at the wrist, ionic conductances were altered at the node, or that the size of the node was increased, possibly as a result of immune-mediated damage. The anti-voltage-gated potassium channel antibodies thought to generate peripheral nerve hyperexcitability in acquired neuromyotonia may be indirectly responsible for changes in motor axon nodal membrane properties.

Adult↗
PubMed1999

Do the same genes predispose to Gilles de la Tourette syndrome and dystonia? Report of a new family and review of the literature.

Gilles de la Tourette syndrome (TS) and idiopathic focal torsion dystonia are both movement disorders in which the pathologic process is thought to arise within the basal ganglia. However, despite their possible functional links, they are clinically distinct and are generally considered to have different underlying etiologies. There are several reports in the literature that suggest a relationship between eye winking tics, excessive blinking, and blepharospasm and a report of the coexistence of tics and dystonia. We describe a three-generation family in which TS and dystonias cosegregate. In total, eight patients were affected, five with dystonia and three with TS/facial tics. One of the patients with historic evidence of dystonia subsequently died of motor neuron disease. The identification of this family further strengthens the evidence in favor of an etiologic relationship between some cases of Gilles de la Tourette syndrome and focal dystonia.

Adult↗
PubMed1999

Signal-, set-, and movement-related activity in the human premotor cortex.

Single unit recording studies in non-human premotor cortex have revealed neurons with motor-related activity. Other neurons, however, seem to be involved in prior movement selection and preparation processes, and have activity related to visual instruction signals or movement preparation ('set'). We have used single pulse transcranial magnetic stimulation (TMS) to identify similar processes in human subjects. In Experiment 1 subjects performed a cued movement task while being stimulated with TMS over three sites: sensorimotor cortex, posterior premotor cortex and anterior premotor cortex. TMS slowed movements when applied at 140 ms after the visual cue over the anterior premotor site, at 180 ms after the visual cue over the posterior premotor site, and at 220 ms and later after the visual cue over the sensorimotor cortex. The results are consistent with a change from signal to movement-related processing when moving from premotor to motor cortex. In Experiment 2 there was a preparatory set period between the instruction signal that informed subjects which movement to make and the 'go' signal that informed them when to actually make the movement. TMS was applied over the anterior premotor site and the sensorimotor site during the set period. At both sites TMS had similar effects on slowing subsequent movements. The results suggest set activity in both premotor and motor cortices in human subjects.

Brain↗
PubMed1999

Motor root conduction in neuralgic amyotrophy: evidence of proximal conduction block.

OBJECTIVE: To determine the presence and role of proximal conduction block in neuralgic amyotrophy. METHODS: Percutaneous electrical stimulation of cervical roots and brachial plexus was employed in eight patients with neuralgic amyotrophy. Root to Erb's point compound muscle action potential amplitude ratios for abductor digiti minimi, extensor digitorum communis, biceps, and deltoid muscles were compared with results obtained from 10 healthy controls. RESULTS: Conduction block in the nerve to one muscle was found in three of eight patients (38%) suggesting focal proximal demyelination. Repeat studies showed axonal degeneration, resolution, and persistence of conduction block in these three patients respectively. CONCLUSION: Focal conduction block plays a significant part in the pathogenesis of neuralgic amyotrophy, which is generally regarded as an axon loss process. Therapeutic intervention should be directed to patients with persistent conduction block, with the aim of eradicating the block and possibly minimising subsequent axon loss.

Adult↗
PubMed1998

Peripheral and central motor conduction in amyotrophic lateral sclerosis.

Conventional peripheral motor conduction studies and transcranial magnetic stimulation (TMS) studies, to measure central motor conduction time (CMCT), to the first dorsal interosseous muscle (FDI) were performed on 65 patients with amyotrophic lateral sclerosis (ALS). The hands of each patient were classified into one of four groups depending on the presence of physical signs of lower motor neurone (LMN) and/or upper motor neurone (UMN) involvement. Statistical analysis was made of the results from patients compared with previously established normal values and with those from a control group of 53 normal subjects. Results between the four groups of patients were compared in order to assess any correlation between neurophysiological findings and physical signs. A reduction in the amplitude of compound muscle action potentials (CMAP), prolongation of distal motor latency (DML) and F wave latency were found in 36%, 34% and 19% of hands respectively. These abnormalities were more common in hands with LMN signs. In nine hands, prolongation of DML occurred in the absence of muscle wasting or weakness. CMCT abnormalities were present in 17% of patients with ALS but did not appear to correlate with physical signs.

Action Potentials↗
PubMed1998

Acquired neuromyotonia in a patient with spinal epidural abscess.

We report a case of acquired neuromyotonia in a patient with Staphylococcus aureus septicemia and a spinal epidural abscess. Autoantibodies to voltage-gated potassium channels, which are associated with acquired neuromyotonia, were present during the patient's acute illness but became undetectable on clinical recovery. The spinal epidural abscess may have triggered the production of these specific autoantibodies, resulting in clinically and electromyographically detectable neuromyotonia.

Abscess↗
PubMed1998

Effect of 3,4-diaminopyridine on the time course of decay of compound muscle action potential augmentation in the Lambert-Eaton myasthenic syndrome.

3,4-Diaminopyridine (3,4-DAP) is known to be beneficial in the symptomatic treatment of the Lambert-Eaton myasthenic syndrome (LEMS). The effects of 3,4-DAP on the decay of postexercise augmentation were observed in 6 patients with LEMS. After 10 s maximal voluntary contraction, the amplitude of the compound muscle action potential (CMAP) recorded from abductor digiti minimi decayed exponentially after an initial rise. The rate of decay in CMAP amplitude was increased after treatment with 3,4-DAP, suggesting that this drug has an effect on the efflux of calcium ions from the presynaptic nerve terminal.

4-Aminopyridine↗
PubMed1998

Covariation between human intrinsic hand muscles of the silent periods and compound muscle action potentials evoked by magnetic brain stimulation: evidence for common inhibitory connections.

Transcranial magnetic stimuli at different stimulus intensities were applied in six healthy subjects to test the hypothesis that, in different intrinsic hand muscles, the duration of the resultant cortically evoked silent periods (C-SPs) from each stimulus would be positively correlated between muscles, indicating a common inhibitory mechanism. A figure-of-eight coil discharging through a Magstim 200 stimulator delivered 25 stimuli at each stimulus intensity at a minimum of five intensities ranging from 55% to 160% of the individual resting motor threshold. In each subject, simultaneous surface recordings from pairs of muscles were made from the first dorsal interosseous (FDI), opponents pollicis (OP), abductor pollicis brevis (APB) and abductor digiti minimi (ADM). The C-SP durations within all three muscle pairs tested were highly correlated (P<0.001). The amplitude of the preceding compound-muscle action potentials (CMAPs) was positively correlated between FDI and OP, but not between APB and ADM or FDI and ADM. C-SP duration was linearly related to stimulus intensity, but did not correlate with the latency or amplitude of the preceding CMAP. SPs elicited by peripheral nerve stimuli in pairs of hand muscles did not co-vary significantly. The results provide evidence that inhibitory influences of cortical origin are distributed widely to intrinsic hand muscles. In contrast, covariation of excitatory effects only appears between muscles synergistically involved in a motor task.

Action Potentials↗
PubMed1998

Temporary interference in human lateral premotor cortex suggests dominance for the selection of movements. A study using transcranial magnetic stimulation.

It is known that damage to the left hemisphere can lead to movement deficits, and that patients with apraxia have difficulty in selecting movements. Neurophysiological recording studies and lesion studies have shown that the premotor cortex is important for the selection of movements in monkeys. In this study we used transcranial magnetic stimulation (TMS) to disrupt the processing in human premotor cortex. We applied TMS to normal healthy volunteers over the premotor and primary motor areas while they carried out choice reaction time and simple reaction-time tasks. We measured response times of either hand as subjects were stimulated over the left and right hemisphere separately. We found that we were able to delay responses by stimulating at short cue-stimulus intervals (100-140 ms) over premotor cortex and at longer cue-stimulus intervals (300-340 ms) over primary motor cortex while subjects performed the choice reaction-time task with the contralateral hand. We were also able to delay responses with the ipsilateral hand while stimulating over the left premotor cortex, but not while stimulating over the right premotor cortex or either sensorimotor cortex. Premotor cortex stimulation alone disrupts an early stage of movement selection; motor cortex stimulation disrupts the movements at a later stage of execution. There was no distinguishing short cue-stimulus interval effect when premotor cortex was stimulated in the simple reaction time paradigm, where the movement selection demands of the task are kept to a minimum. We conclude that the premotor cortex is important for selecting movements after a visual cue and that the left hemisphere is dominant for the rapid selection of action.

Analysis of Variance↗
PubMed1998

Distribution of electrophysiological abnormality in Lambert-Eaton myasthenic syndrome.

OBJECTIVE: To assess the distribution of electrophysiological abnormality in Lambert-Eaton myasthenic syndrome (LEMS) to identify the most sensitive muscle to use in routine examination. METHODS: Surface recorded compound muscle action potential (CMAP) amplitudes were made from abductor digiti minimi, abductor pollicis brevis, anconeus, biceps brachii, and trapezius in 10 patients with LEMS. The effect of 3,4-diaminopyridine (3,4-DAP) was recorded in each muscle in nine patients. CMAP amplitudes were measured at rest and immediately after 10 seconds maximal voluntary contraction in each muscle. Values were compared with results obtained from 12 healthy controls. RESULTS: Resting CMAP amplitudes were reduced in at least one muscle in all patients compared with controls, most markedly in abductor digiti minimi and anconeus. The administration of 3,4-DAP resulted in significantly improved resting CMAP amplitudes in trapezius only. After maximal voluntary muscle contraction, characteristic increments in CMAP amplitude of over 100% above resting values were seen in abductor digiti minimi and abductor pollicis brevis in seven patients, anconeus and biceps brachii in five patients. No patient had this level of increment in trapezius. CONCLUSION: Despite predominantly proximal limb weakness seen clinically in patients with LEMS, the most sensitive muscles for detecting characteristic electrophysiological abnormalities of low resting CMAP amplitude and increment of over 100% after 10 seconds maximal voluntary contraction are abductor digiti minimi, abductor pollicis brevis, and anconeus.

4-Aminopyridine↗
PubMed1998

Decay of postexercise augmentation in the Lambert-Eaton myasthenic syndrome: effect of cooling.

The effect of local cooling on surface recorded compound muscle action potential (CMAP) amplitude was studied in five patients with the Lambert-Eaton myasthenic syndrome (LEMS). The time course of decay of postexercise augmentation of CMAP amplitude characteristically seen in patients with LEMS was determined. We recorded the CMAP from abductor digiti minimi (ADM) in response to supramaximal stimulation of the ulnar nerve. Thirty consecutive stimuli were delivered at 1 Hz immediately after a 10-second period of maximal voluntary contraction. Skin surface temperature was recorded throughout. Initial testing at approximately 30 degrees C was repeated after cooling the hand and forearm by 6 to 12 degrees C. The effects of blood flow on temperature were counteracted by the application of a sphygmomanometer cuff, inflated above systolic blood pressure. The CMAP amplitude following contraction decayed in an exponential manner both during warm and cold conditions. The mean time constant for decay (1/b) in all patients was increased by approximately 25% after cooling. This prolongation of the period of postexercise augmentation of CMAP amplitude in LEMS after cooling concurs with patient reports of symptomatic improvement in cold weather. The mechanism for this benefit is thought to be due to reduction in the rate of removal of calcium ions from the nerve terminal following stimulation, similar to that seen in animal models of short-term synaptic enhancement.

Action Potentials↗
PubMed1997

Corticomotor threshold to magnetic stimulation: normal values and repeatability.

The threshold for corticomotor excitation by magnetic stimuli is a clinically important parameter in the assessment of central motor conduction. Hitherto, arbitrary criteria have been adopted to define threshold and there are few published data using a figure of eight coil. A new method is described in which the highest stimulus intensity evoking responses in the relaxed first dorsal interosseous muscle with a probability of zero [lower threshold (LT)] and the lowest intensity evoking responses with a probability of one [upper threshold (UT)] have been determined. The method, which utilizes a coil located and optimally oriented over hand motor cortex, minimizes the number of stimuli needed. Both LT and UT are normally distributed and are independent of age, gender, and hemisphere. In 102 healthy hands of 55 control subjects 23-84 years of age, mean +/- SD UT was 46.6 +/- 9.4% and LT was 38.0 +/- 8.6% maximum stimulator output. Repeatability estimates indicated an absolute change of more than 13% or 11% in UT or LT respectively in the same individual over 1-3 months was significant at the 5% level.

Adolescent↗
PubMed1997

Corticomotor threshold is reduced in early sporadic amyotrophic lateral sclerosis.

The pathogenesis of idiopathic amyotrophic lateral sclerosis (ALS) remains unknown, but accumulating evidence suggests a neuroexcitotoxic mechanism may have some credence. Glutamate-induced hyperexcitability of cortical or spinal motoneurons may be expected to manifest itself as a reduced threshold for activation of these structures. We have measured corticomotor threshold to the first dorsal interosseous (FDI) muscles of 48 patients with sporadic ALS using magnetic brain stimulation and have correlated the findings with physical signs of upper and/or lower motor neuron degeneration. We find that if FDI in patients with ALS shows no weakness, wasting, or signs of an upper motor neuron lesion, mean corticomotor threshold is significantly lower than in 102 healthy control FDI muscles (P = 0.02). In contrast, FDI muscles showing signs of lower motor neuron degeneration only or mixed upper and lower motor neuron signs are associated with a raised corticomotor threshold (P = 0.008, P < 0.001, respectively). We conclude that early in ALS, at a time when hand muscle function is normal, corticomotor threshold is reduced and suggest that this may be a manifestation of abnormal excitability of cortical or spinal motoneurons to neurotransmitters, whose action will ultimately lead to cell death.

Aged↗