Biomedical subjects
Publications and source records attributed to P Ashby.
Two patients with movement disorders associated with syringomyelia are described, one of whom developed unusual torticollis, and the other had choreoathetoid-dystonic movements of the hand and arm. In each case, the movements resolved with decompression of the syrinx. The literature is reviewed and possible mechanisms explored.
We investigated the nature of the silent period (SP) following transcranial magnetic stimulation by recording corticospinal volleys in a patient with implanted cervical epidural electrodes. Single suprathreshold test stimuli and paired stimuli at interstimulus intervals (ISIs) of 50-200 ms were delivered while the subject maintained a constant background contraction. The silent period duration from a single test stimulus was 357+/-62 ms. The test motor-evoked potentials were markedly reduced at all the ISIs tested. The I (indirect) waves induced by the test stimulus were largely unchanged at an ISI of 50 ms, suggesting that there was little change in motor cortex excitability. However, the corticospinal volleys, especially the late I waves, were substantially reduced at ISIs of 100 ms, 150 ms, and 200 ms. Our findings suggest that the early part of the SP is mainly due to spinal mechanisms, while the late part of the SP is related to reduced motor cortex excitability.
OBJECTIVE: To find the area of the human cortex from which inhibition and facilitation of corticospinal neurons could be obtained. METHODS: A patient with seizures had an array of 64 electrodes placed over the left fronto-temporal cortex. The motor evoked potential (MEP) elicited by stimulating through one pair of electrodes was conditioned by stimuli that were subthreshold for a MEP given through adjacent pairs of electrodes. RESULTS: The MEP recorded over the right abductor pollicis brevis produced by stimulating over the hand area of the left cortex could be inhibited (at intervals less than 5 ms) and facilitated (at intervals greater than 5 ms) by subthreshold conditioning stimuli delivered through neighbouring pairs of electrodes. The inhibition and facilitation were only obtained when the conditioning stimuli were delivered within 1-2 cm of the test site. The sites producing inhibition and facilitation were not identical. Conditioning stimuli over the face area did not inhibit the MEP produced by stimulating the hand area or vice versa. CONCLUSION: The inhibition and facilitation of corticospinal neurons projecting to a given muscle arise from small areas close to those corticospinal neurons.
OBJECTIVE: To study the mechanism of cortical reflex myoclonus. METHODS: A patient with stimulus sensitive myoclonus of the left foot had an array of subdural electrodes placed over the right sensorimotor cortex. RESULTS: Stimulation through one of the electrodes (contact 13) facilitated leg muscles with the shortest latency and was presumed to lie over the motor cortex. Tibial nerve stimulation evoked a potential with the shortest latency 1 cm further posteriorly (contacts 11-12). These contacts were presumed to lie over the sensory cortex. The potential at 11-12 was followed by a much larger potential that reversed polarity at contact 13. Back averaging from spontaneous myoclonic jerks showed a cortical premovement potential which reversed polarity at contact 13. The threshold for the motor evoked potential in leg muscles evoked by transcranial magnetic stimulation was lower on the affected side. Electrical stimulation through contact 13 produced cortical potentials that could be recorded at adjacent contacts. The combination of a positive potential followed by a negative potential recurred at approximately 35-40 ms intervals, each positive potential generating a myoclonic jerk. Additional waves resembling I waves accompanied only the first positive potential. Surgical removal of the cortex under electrode 13 abolished the myoclonus. CONCLUSIONS: The myoclonic jerks arose in the motor cortex. We postulate that there is increased excitability or synchronization of the cortical neurons at that site. The spontaneous, peripherally induced and recurrent cortical potentials and myoclonic jerks can occur without participation of the circuitry of the presumed I waves.
The effects of stimulation through macroelectrodes implanted in the subthalamic nucleus (STN) were studied in 14 patients with parkinsonism. Single stimuli delivered directly to the STN electrodes with an external stimulator modulated voluntary electromyography (EMG) of contralateral muscles in most patients. A short-latency facilitation ('peak') was attributed to the activation of the corticospinal system. A longer latency inhibition ('dip'), often preceded or followed by facilitations, appeared to arise from the activation of large-diameter fibres running parallel to the electrode and to be transmitted through the motor cortex. It is possible that the dip could result from the inhibition of thalamocortical neurons. With high-frequency stimulation ( approximately 100 Hz) the peaks occurred at the stimulus frequency; the dips became confluent and outlasted the duration of the stimulus train. There was no evidence that high-frequency stimulation produced 'blocking'. The studies were repeated in 12 patients a mean of 5.8 months after implantation of the stimulator. The same short-latency effects were obtained. They were present on 7 out of 23 sides at the settings in use and on the majority of sides if the stimulus intensity was slightly increased. There was no clear relationship between these short-latency effects and the patients' overall clinical improvement; the effects may result from the spread of current to large-fibre systems near the STN. In five patients, high-frequency stimulation on one side immediately reduced tremor in the contralateral limbs. This effect arose from the activation of large-diameter fibres and, like the dip, had about the same threshold at each of the contacts. Frequencies as low as 70 Hz were sufficient. We conclude that the control of tremor by STN stimulation is due to the activation of a large-fibre system.
Familial amyloid polyneuropathy is an autosomal dominant disorder in which the liver produces a variant prealbumin that is deposited along nerves, leading to a progressive and fatal polyneuropathy that begins in the third decade of life. Liver transplantation has been the only successful treatment to date. Apart from the production of the variant protein, there are no other abnormalities in these amyloid livers. We describe two cases in which, at the time of transplantation, the amyloid livers were subsequently used for transplantation in another patient, and we discuss the implications.
The immediate motor effects of stimulation through electrodes chronically implanted in the globus pallidus internus (GPI) were studied in 9 subjects with Parkinson's disease. Single stimuli (at >>0.4 Hz) produced short latency facilitation of voluntarily activated contralateral muscles in all subjects. The latency and distribution of the facilitation, its probably monosynaptic nature, and the short chronaxie and refractory period of the activated neural elements suggest that the facilitation results from the direct excitation of the fast conducting corticospinal pathway. The facilitation of motoneurons followed high frequency (e.g. 200 Hz) stimulation without decrement and occurred at stimulus intensities well below those required to produce a visible muscle contraction. We conclude that, while there may be other effects, GPI stimulation through electrodes may activate the corticospinal tract, even when the stimuli are below the threshold for a visible muscle contraction, and that continuous stimulation may do so continuously. This may be an unwanted side effect, but possible therapeutic actions are considered. The reproducible short latency facilitation enabled us to estimate current spread from the quadripolar electrodes used for deep brain stimulation. When the current is sufficient to excite large myelinated fibers near one of the quadripolar electrodes, an additional 1-mA current will activate similar fibers at an additional distance of 1.8 mm with bipolar stimulation and at a distance of 5.7 mm with monopolar stimulation.
Twenty-two Flexor Digitorum Superficialis (FDS) muscles from 18 cadavers were dissected to find the "Optimal Injection Site" (OIS) for botulinum toxin injections to individual bellies of FDS. Coordinates are given as a percentage of the distance along a landmarking line from the medial epicondyle to the pisiform and in millimetres (mm) lateral to it. The OIS were: FDS2: 72%, 14 mm; FDS3: 54%, 17mm; FDS4: 49%, 7mm; FDS5: 76%, 6mm. OIS measurements guide the electromyographer to localize the targeted muscle belly.
The short-latency reflex myoclonus that appears to be characteristic of cortical-basal ganglionic degeneration (CBGD) was investigated in two patients. Stimulating the digital nerves of the middle finger caused exaggerated reflex activity in the first dorsal interosseus (FDI) muscle of that hand with a latency of 46-51 ms. Magnetic stimulation over the contralateral cortex, delivered 25 ms after the digital nerve stimulus, resulted in greater than expected facilitation of FDI, implying spatial summation. Poststimulus time histograms (PSTH) of individual FDI motor units indicated that this spatial summation was occurring "upstream" from the motoneurons. It is argued that this occurs at the motor cortex. Magnetic stimulation over the cortex in normal subjects results in short-latency facilitation of the contralateral motoneurons followed by inhibition. This inhibition was less in the patients with CBGD. It is argued that this results from the loss of an intrinsic cortical and corticothalamic inhibitory mechanism.
The motor effects of stimuli delivered through four-channel, quadripolar macroelectrodes chronically implanted in the ventrolateral thalamus were studied in 20 awake cooperating human subjects. Single stimuli could inhibit voluntary contraction of the contralateral first dorsal interosseous muscle (FDI) for up to 200 ms. The inhibition was often followed by a rebound facilitation or by oscillatory activity. This inhibition appeared to arise from the ventrolateral thalamus and could not be obtained in other patients by stimulation of the periventricular grey matter (PVG), the globus pallidus internus (GPI), or the subthalamic nucleus (STN). The neural elements activated by the stimulus had a short chronaxie and a short refractory period, implying that they were large-diameter axons. Similar effects were obtained from each of the four electrodes in the row, suggesting that this fiber system lay parallel rather than perpendicular to the implanted macroelectrode. The inhibition resulting from a single stimulus was diminished by a prior stimulus or train of stimuli. A continuous train of stimuli produced inhibition for only the first 200 ms. We propose that the thalamic stimulus activates a neural network which includes thalamic relay cells and neurons of the thalamic reticular nucleus and that the inhibition of thalamic relay cells habituates with repeated stimuli. It has been suggested that parkinsonian rest tremor results from synchronization of the oscillatory activity of this network. If this is the case, continuous thalamic stimulation might disrupt this oscillation by diminishing the inhibitory phase.
This study examined the effects of intravenous administration of sodium amytal (SA), a medium action barbiturate, on cutaneous limb temperatures and sympathetic skin responses (SSR) to electrical stimulation. Eight normal volunteers and 13 patients with musculoskeletal pain, somatoform pain disorders or nerve/root injury (with findings strictly limited to the distribution of the distribution of the involved nerve) were compared to 15 patients with Complex Regional Pain syndromes (one of whom had documented nerve injury). The Complex Regional Pain Syndromes (CRPS) patients were characterized by the presence of severe diffuse limb pain and extraterritorial sensory, sudomotor and vasomotor abnormalities (i.e., not confined to the site of injury or the distribution of the injured nerve). The CRPS patients were different from the normal controls and the non-CRPS patients in their tendency to warm significantly many of their limbs (not just the symptomatic ones). SSR were reduced or lost in a few limbs only in all three groups, irrespective of the increase or decrease of limb temperature and the side of symptoms. We argue that the enhanced thermogenic effect of SA in CRPS patients is due to generalized central changes of thermoregulatory control specifically in this group.
BACKGROUND: Pallidotomy helps parkinsonian symptoms. We tested the hypothesis that this might be due to changes in inhibition in the motor cortex. METHODS: We examined 15 patients with parkinsonism before and after posteroventral pallidotomy. Magnetic stimuli were delivered over the motor cortex, while subjects maintained a 30% maximum voluntary contraction of the contralateral first dorsal interosseus (FDI). RESULTS: Weak stimuli inhibited voluntary muscle activity, while slightly stronger stimuli caused short latency facilitation from activation of the corticospinal neurons. After pallidotomy magnetic stimulation, at the threshold for the short latency facilitation, resulted in more inhibition than before. CONCLUSION: Pallidotomy increases cortical inhibition. This may be associated with improved control of movements.
BACKGROUND: There is currently no consensus on the best way to localize muscles in the forearm for botulinum toxin (BTX) injection. We devised a study to compare electromyography (EMG) with local stimulation through a cannula for localizing forearm muscles for botulinum toxin (BTX) injection, and for predicting the risk of unwanted weakness in non-target muscles. METHODS: In 12 patients with focal hand dystonia a single "target" muscle, determined by clinical examination to contribute most to the dystonic hand posture, was selected for botulinum toxin injection. The patients were randomized into 2 treatment groups, one in which the target muscle was localized by recording the EMG signals during voluntary contractions (8 patients) and the other in which the target muscle was localized by local electrical stimulation (4 patients). The target muscle was then injected with a standardized dose of BTX. RESULTS: At follow-up 3 weeks after BTX injection the target muscle was weakened in 7/12 patients (4/8 of the EMG group, and 3/4 of the stimulation group). Additional noninjected muscles, adjacent to the target muscle, were weakened in 5 of these 7 patients, presumably from diffusion of the toxin. CONCLUSIONS: Localization by stimulation is probably at least as good as EMG. Each technique has certain advantages. Weakness of "non-target" muscles was not consistently predicted by either EMG or stimulation suggesting that BTX diffuses farther than the volume conduction of EMG signals or the spread of effective stimulus current.
A ballistic movement of one arm may be accompanied by contractions of contralateral postural muscles known as "associated postural adjustments." Ballistic movements are considered to involve the motor cortex, but it is not known where associated postural adjustments are generated. We recorded the EMG activity in the deltoid and latissimus dorsi muscles during ballistic abduction of the arm in 10 normal subjects and five subjects with lesions of the motor cortex. When subjects with cortical lesions abducted the unaffected arm, the associated postural adjustment in the contralateral latissimus dorsi was significantly smaller than normal. We argue that postural adjustments, like ballistic movements, require the participation of the motor cortex.
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1. Observations were made on seven human subjects with electrodes implanted in the cerebellar thalamus for the control of tremor. 2. Weak stimulation at 1-2 Hz resulted in sudden lapses of posture of actively contracting contralateral limb muscles. Stronger stimuli caused muscle twitches even in relaxed muscles. 3. The stronger stimuli produced short latency facilitation of EMG activity in contralateral muscles; the pattern of muscle facilitation, the conduction velocity of the descending pathway and the estimated rise time of the underlying composite EPSP were consistent with direct activation of the corticospinal tract. 4. The lapses of posture produced by the weaker stimuli were associated with inhibition of ongoing EMG for up to 150 ms. This was due to the interruption of tonic drive to motoneurons rather than to their inhibition and was associated with depression of the motor evoked potential in relaxed muscles produced by weak anodal transcranial stimulation. The inhibition could be produced by 0.1 ms pulses, implying that a large-diameter fibre system was being activated. 5. A number of mechanisms could contribute to the inhibition, including inhibition from the reticular nucleus of the thalamus.
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BACKGROUND: We tested the effect of thiopental on the excitability of the corticospinal-motoneuron axis in normal human subjects. METHODS: Magnetic stimulation was used to excite the neurons in the motor cortex which give rise to the fast conducting corticospinal pathway. The characteristics of the composite excitatory post-synaptic potentials (EPSPs) produced in individual spinal motoneurons by cortical stimulation were derived from changes in the firing probability of voluntarily activated motor units of the first dorsal interosseous muscle. RESULTS: In 5 normal subjects, we found that thiopental, in incremental doses sufficient to sustain drowsiness (total dose 75 to 175 mg), significantly reduced the amplitude of these composite EPSPs. CONCLUSIONS: Thiopental reduced the facilitation of motoneurons from the cortex most likely by depressing cortical neurons.