The clinical usefulness of magnetic cortical stimulation.
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Publications and source records attributed to N M Murray.
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Magnetic stimulation of the motor cortex is of value in the diagnosis and management of several neurological disorders. Marked latency prolongation is suggestive of demyelination of central motor pathways, whereas low-amplitude responses with little delay are more typical of disorders causing neuronal loss or axonal degeneration. Subclinical abnormalities may be demonstrated, and the technique has a potential role for quantification and monitoring of disease progress. The pattern of early electrophysiological abnormality is of prognostic value in stroke patients.
The maintenance of axial atonia during REM sleep was monitored in 14 patients with primary torsion dystonia, 10 patients with secondary torsion dystonia, and 10 normal subjects using submental EMG and video EEG telemetry. The excitability of the corticospinal tract during REM sleep was also assessed using scalp magnetic stimulation in seven patients and three controls. During REM sleep dystonic patients had well maintained atonia evidenced by infrequent bursts of submental activity, no episodes of complex semi-purposeful behaviour and reduced motor responses to magnetic stimulation. These findings suggest that the inhibitory centres in the region of the locus coeruleus and their descending pathways to the spinal alpha motor neurons are intact in torsion dystonia.
Activity in descending motor pathways after scalp electrical and magnetic brain stimulation of the motor cortex was recorded from the exposed cervico-medullary junction in six patients having trans-oral surgery of the upper cervical spine. Recordings during deep anaesthesia without muscle paralysis revealed an initial negative potential (D wave) at about 2 ms with electrical stimulation in five of the six patients. This was followed by a muscle potential which obscured any later waveforms. Magnetic stimulation produced clear potentials in only one patient. The earliest wave to magnetic stimulation during deep anaesthesia was 1-2 ms later than the earliest potential to electrical stimulation. Following lightening of the anaesthetic and the administration of muscle relaxants a series of later negative potentials (I waves) were more clearly seen to both electrical and magnetic stimulation. More I waves were recorded to magnetic stimulation during light anaesthesia than during deep anaesthesia. Increasing the intensity of electrical stimulation also produced an extra late I wave. At the highest intensity of magnetic stimulation the latency of the earliest potential was comparable to the D wave to electrical stimulation. The intervals between these various D and I waves corresponded to those previously described for the timing of single motor unit discharge after cortical stimulation.
One hundred and fifty patients presenting with small cell lung cancer (SCLC) to chest physicians, were assessed neurologically. Neuromuscular or autonomic deficits were common and occurred in up to 44% of cases. Weakness, dry mouth, and weight loss were not mutually independent and may represent the syndrome formerly described as carcinomatous neuromyopathy. By contrast, undoubted paraneoplastic syndromes were much less commonly detected. Two patients had the Lambert-Eaton myasthenic syndrome (LEMS) and one had subacute sensory neuropathy (SSN). In these patients, neurological symptoms antedated other manifestations of cancer, by between six and 17 months. The 95% confidence interval for the prevalence of LEMS or SSN among SCLC patients was 0-4%, consistent with the results of previous retrospective or smaller studies: summing these, the overall prevalence of LEMS among SCLC patients is close to 3%, which implies about 250 new cases per annum in England and Wales. If LEMS and SSN are the least uncommon neurological paraneoplastic syndromes in SCLC patients, this may reflect the accessibility of motor nerve terminals and dorsal root ganglia to cross-reactive anti-tumour cell antibodies.
Central motor conduction to the small hand muscles was investigated in 59 patients with peroneal muscular atrophy and hereditary spastic paraplegia (HSP) by using transcranial magnetic brain stimulation. These comprised 20 patients with type I hereditary motor and sensory neuropathy (HMSN I), 15 with type II (HMSN II), 4 with HMSN I and 10 with HMSN II with associated pyramidal features, and 10 with the "pure" form of HSP. Central motor conduction was usually normal in HMSN I, HMSN II, and HSP. In HMSN I with pyramidal signs, central motor conduction time was greatly prolonged bilaterally. This result may reflect an associated involvement of the central motor pathways in these patients. In HMSN II with accompanying pyramidal features, 6 of the 10 patients had abnormal central motor conduction, although conduction times were only slightly prolonged, suggesting a different pathophysiological pattern.
The voltage measured was that induced in a measuring coil from 3 different commercially available magnetic stimulators. The strongest stimulus was from the Cadwell, followed by Novametrix and then Digitimer. The Digitimer and Novametrix produced a monophasic pulse, whilst the Cadwell stimulator produced a polyphasic pulse, all measured by an induction coil. This is thought to be the reason why reversed coil polarity does not influence the position of peripheral nerve excitation with a Cadwell stimulator; this is, however, the case with the two other magnetic stimulators. Nevertheless, electrical stimulation was found to be the most useful method for exciting peripheral nerves. The lack of influence of Cadwell coil polarity on the excitation of spinal roots and motor cortex is also thought to be due to the bipolar stimulus effect mentioned above. The stimuli induced by Digitimer and Novametrix are monophasic, exciting one hemisphere first, depending on the direction of the current impulse. The stimulus generated by Cadwell excites both hemispheres by reversal of current direction.
In a consecutive series of 30 patients with chronic inflammatory demyelinating polyneuropathy (CIDP) minor clinical evidence of CNS involvement was found in five. Cranial magnetic resonance imaging (MRI) was performed in 28 and revealed abnormalities consistent with demyelination in nine patients aged less than 50 years and abnormalities in five aged 50 years or over. Measurements of central motor conduction time (CMCT) were obtained in 18 and showed unilateral or bilateral abnormalities in six. It is concluded that subclinical evidence of central nervous system (CNS) involvement is common, at least in patients with CIDP in the United Kingdom, but that clinically evident signs of CNS disease are infrequent. The association of a multiple sclerosis-like syndrome with CIDP is rare.
We evaluated the outcome in 16 patients with Lambert-Eaton myasthenic syndrome (LEMS) associated with histologically verified small-cell carcinoma (SCC). Thirteen patients received specific tumor therapy (chemotherapy, radiation therapy, or resection) and most also received pharmacologic and immunologic treatment for LEMS. Seven of 11 patients surviving for more than 2 months after tumor therapy showed substantial neurologic improvement (1 patient being in complete remission at 7 years); in 3 of 11 improvement was transient. An EMG index of disease severity (compound muscle action potential amplitude in abductor digiti minimi) was significantly increased at final follow-up (p less than 0.01; n = 11). A pretreatment amplitude greater than 3.0 mV was a good prognostic sign. We conclude that a combined treatment approach in SCC-LEMS usually results in neurologic improvement.
We compared the effects of Lambert-Eaton myasthenic syndrome (LEMS) immunoglobulin G (IgG) obtained from patients with and without small-cell lung carcinoma (SCLC) on voltage-gated (K+-stimulated) 45Ca2+ flux in cell lines derived from a human SCLC (MAR10) and from a rat pheochromocytoma (PC12) and related these to electromyographic indexes of clinical severity. Control IgG was obtained from patients with other neurological disorders or healthy individuals. Inhibition of Ca2+ flux by LEMS IgG was time and dose dependent. The flux was significantly reduced in MAR10 cells grown in either SCLC-LEMS IgG (0.38 nmol/10(6) cells; p less than 0.001) or non-SCLC-LEMS IgG (0.35 nmol/10(6) cells; p less than 0.001), compared with that in MAR10 cells grown in control IgG (0.7 nmol/10(6) cells). Similar significant reductions were also observed in PC12 cells. The reduction in amplitude of the resting compound muscle action potential in the LEMS patients correlated positively (r = 0.70; p = 0.007) with the inhibition of Ca2+ flux in MAR10 cells by their IgG. These results strongly support the view that IgG autoantibodies that can inhibit Ca2+ flux in SCLC cells are responsible for the disorder of transmitter release at motor nerves in SCLC-associated LEMS.
Short mechanical stretches given to partially activated human abductor digiti minimi muscle (ADM) evoke early (M1) and late (M2) reflex responses. Transcranial magnetic brain stimuli were used to evoke compound muscle action potentials in ADM and hence to estimate motoneuronal excitability at various times after mechanical stimuli. There was no evidence that Ia volleys produce additional facilitation in motoneurones of muscles which are already voluntarily activated. However, the inhibitory phase between M1 and M2 was associated with a reduction in size of muscle responses from brain stimuli. This may reflect reduced Ia input, polysynaptic Ia inhibition or Renshaw inhibition.
Transcranial magnetic brain stimuli were applied to 9 normal subjects and compound muscle action potentials were recorded from the right abductor digiti minimi with surface electrodes. Vibration of 120 Hz, 0.6 mm peak to peak amplitude, applied to the muscle tendon enhanced its responses to magnetic brain stimuli. This facilitation corresponds to the tonic vibration reflex. Inhibition of muscle responses was not seen with vibration. Thus it is likely that the known inhibition of stretch reflexes by vibration is purely presynaptic. Small rectangular mechanical stimuli (rise time 200 mm/s, amplitude 1 mm) applied to ADM elicited short and long loop reflex responses. When brain stimuli were give 7-16 ms after the muscle tap, muscle responses were enhanced. It is argued that this is a result of the summation of the effects of Ia afferent impulses and descending pyramidal volleys at the alpha motoneurones. A separate late facilitation corresponding with the arrival of muscle afferent inputs to the sensori-motor cortex was not seen.
Transcranial magnetic brain stimuli were delivered to 6 healthy subjects at different time intervals after the beginning of muscle vibration. Vibration of 6 sec duration in 4 subjects and of 100 msec duration in 6 subjects was applied to the right abductor digiti minimi muscle using an electromagnetic mechanical stimulator. The responses to brain stimuli were enhanced in this muscle when vibration began 9 msec before the transcranial stimulus, i.e., when the descending volley and the monosynaptic afferent Ia volley arrived simultaneously at the anterior horn cell. With long lasting vibration an enhancement of responses to brain stimuli was seen, which began after 120 msec and continued for up to 5 sec after the onset of vibration. This is consistent with a tonic, probably polysynaptic, excitatory Ia influence on homonymous alpha motoneurones, as well as the well known monosynaptic effect.
The clinical and electrophysiological features of 50 consecutive patients with the Lambert-Eaton myasthenic syndrome (LEMS) have been analysed. Carcinoma was detected (CD group) in 25, of whom 21 had small cell lung cancer (SCLC). SCLC was evident within 2 yrs of onset of LEMS symptoms in 20/21 cases, and at 3.8 yrs in 1/21. In the cases in whom no carcinoma was detected (NCD group), 14/25 had a history of LEMS greater than 5 yrs. The dominant neurological features were similar in the CD and NCD groups, and consisted of proximal lower limb weakness (100%), depressed tendon reflexes (92%) with posttetanic potentiation (78%), autonomic features, especially dryness of the mouth (74%) and mild/moderate ptosis (54%). The compound evoked muscle action potential amplitude in abductor digiti minimi was below the lower limit of control values in 48/50, and the increment following maximum voluntary contraction above the upper limit of control values in 48/50. Single fibre electromyographic abnormalities were found in 29/29 cases. The analysis indicates that a patient presenting with LEMS has a 62% risk of an underlying SCLC, and that this risk declines sharply after 2 yrs, becoming very low at 4 to 5 yrs. It is argued that in SCLC cases antigenic determinants on tumour cells initiate the autoimmune response, often early in the course of the malignancy, but that the association of LEMS with tumours other than SCLC may be fortuitous. In the latter, and in NCD patients, the initiating factor(s) are unknown.
A magnetic stimulator was used for direct transcutaneous stimulation of the intracranial portion of the facial nerve in 15 normal subjects and in patients with Bell's palsy, demyelinating neuropathy, traumatic facial palsy and pontine glioma. Compound muscle action potentials (CMAPs) thus elicited in the orbicularis oris muscle of controls were of similar amplitude but longer latency (1.3 SD 0.15 ms) compared with CMAPs produced by conventional electrical stimulation at the stylomastoid foramen. No response to magnetic stimulation could be recorded from the affected side in 15 of 16 patients with Bell's palsy. Serial studies in two patients demonstrated that the facial nerve remained inexcitable by magnetic stimulation despite marked improvement in clinical function. In the patient with a pontine glioma, the CMAP elicited by transcranial magnetic stimulation was of low amplitude but normal latency. In six of seven patients with demyelinating neuropathy, the response to intracranial magnetic stimulation was significantly delayed. Magnetic stimulation produced no response in either patient with traumatic facial palsy. Although the precise site of facial nerve stimulation is uncertain, evidence points to the labyrinthine segment of the facial canal as the most likely location.
Central motor conduction to small hand muscles was measured using magnetic stimulation of the motor cortex and electrical stimulation of proximal motor roots in 11 patients with Friedreich's ataxia, 10 patients with early onset cerebellar ataxia with retained tendon reflexes (EOCA) and 13 patients with late onset degenerative cerebellar disease (LOCD). Central motor conduction was abnormal in 91% with Friedreich's ataxia, 70% with EOCA and 38% with LOCD. Central motor conduction abnormalities were not specific to individual disorders but were more severe and were related to disease duration in Friedreich's ataxia and EOCA.
The influence of different mechanical stimuli on the excitability of spinal motoneurones was investigated in 5 different experiments using transcranial magnetic brain stimulation. A servo controlled moving coil was used to deliver rectangular mechanical stimuli or vibration to the right abductor digiti minimi muscle (ADM) thus exciting spindle primaries. With the ADM relaxed, vibration produced an early enhancement of compound responses (CMAPs) after transcranial magnetic brain stimuli. This is thought to be due to simultaneous arrival of the descending corticospinal volley and of the afferent la volley at the anterior horn cell. With long lasting vibration an enhancement of responses to brain stimuli continued up to 5 seconds after the onset of vibration. Voluntary muscle contraction increased the CMAP. CMAPs measured with voluntary muscle contraction plus mechanical muscle stimulation did not differ from those with muscle contraction alone. Therefore an excitatory influence of mechanical stimuli cannot be seen with ADM contracted.
Using concentric needle electrode recording from hand muscles (abductor digiti minimi, first dorsal interosseus, or abductor pollicis brevis muscle) the latencies of single motor unit potentials in response to threshold magnetic brain stimuli were studied under different conditions. It has been shown that the motor units activated by threshold brain stimuli had the lowest threshold for voluntary activation (A = vol. activated, B = brain stim.). Onset latencies of 23 motor unit potentials from different sites in the relaxed muscles of four healthy subjects ranged from 22.4 to 32.4 ms (average: 26.4 ms; SD: 2.80 ms) but proved to be relatively stable when stimulating and recording conditions were kept constant (variation less than 0.5 ms, see poststimulus time histogram in Fig. 2). With concurrent contraction of an ipsilateral neighbouring or of the contralateral homologous muscle the motor unit potentials from the relaxed target muscle jumped to an earlier latency by 1.2 to 1.7 ms (C in Fig. 3 and B-2 in Fig. 4). On one occasion another motor unit of higher threshold was alternatively activated by this procedure (B-3 in Fig. 4). Since the same procedures are known to enhance the compound muscle action potentials as recorded from the relaxed muscle with surface electrodes, the shorter latencies of single motor units are considered to be caused by a facilitatory influence on the motoneurones. A possible explanation for these latency shifts would be that the motor units discharge later in response to the brain stimulus induced repetitive cortico-spinal impulses when there is no facilitation, whereas during facilitation the firing level is reached earlier.(ABSTRACT TRUNCATED AT 250 WORDS)